Clara N Curiel

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Scholarly Contributions

Chapters

• Curiel-lewandrowski, C., Novoa, R. A., Codella, N. C., Giuste, F., Gutman, D. A., Gutman, D. A., Halpern, A. C., Leachman, S. A., Liu, Y., Liu, Y., Reiter, O., Tschandl, P., Curiel, C. N., Celebi, M. E., & Berry, E. G. (2019). Artificial Intelligence Approach in Melanoma. In Melanoma. Springer New York. doi:10.1007/978-1-4614-7322-0_43-1
• Curiel, C. (2016). Methods of Melanoma Detection. In Melanoma(pp 51-107). Springer. doi:10.1007/978-3-319-22539-5
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  Additional co-authors:Sancy A. Leachman, Pamela B. Cassidy, Suephy C. Chen, Alan Geller, Daniel Gareau, Giovanni Pellacani,James M. Grichnik, Josep Malvehy, Jeffrey North, Steven L. Jacques,Tracy Petrie, Susana Puig, Susan M. Swetter, Susan Tofte and Martin A. Weinstock
• Curiel, C. N., Chao, J., & Hofmann-Wellenhof, R. (2014). Cancer Treatment and Research. In Cryosurgery: A Practical Manual. Springer.
• King, S., Curiel-Lewandrowski, C. N., & Chen, S. (2009). Current and Emerging Technologies in Computer Based Diagnosis. In Cancer of the Skin. Saunders Publishing.
• Swetter, S., Curiel, C. N., & Kirkwood, J. (2007). Specific Organ Cancer Prevention: Melanoma. In American Society of Clinical Oncology(pp 24.14-24.25). Alexandria, Virginia.
• Curiel, C. N., & Byers, R. (2003). Cutaneous Lymphomas and Lymphoproliferative Disorders. In Practical Dermatology. Mexico City, Mexico.

Journals/Publications

• Mesgarzadeh, S., Myrdal, C. N., Gong, A. H., Stratton, D. B., Kelly, B. G., & Curiel-Lewandrowski, C. (2025). Heterogeneity among melanoma databases and challenges in sustainability: A survey of the Melanoma Prevention Working Group. JAAD international, 18, 137-139.
• Roland-McGowan, J. N., Freeman, S. C., Baghoomian, W., Carroll, B. T., Kim, C. C., Curiel-Lewandrowski, C., Chu, E. Y., Foster, E. L., Nelson, K. C., White, K. P., Ming, M. E., Hartman, R. I., Leachman, S. A., Mengden-Koon, S., Chen, S. C., Swetter, S. M., Prieto, V. G., Berry, E., & Yu, W. Y. (2025). Development of a Treatment Decision Aid for Patients with Dysplastic Nevi Who Are Candidates for Re-Excision. Journal of the American Academy of Dermatology.
• Dickinson, S. E., Vaishampayan, P., Jandova, J., Ai, Y. E., Kirschnerova, V., Zhang, T., Calvert, V., Petricoin, E., Chow, H. S., Hu, C., Roe, D., Bode, A., Curiel-Lewandrowski, C., & Wondrak, G. T. (2024). Inhibition of UV-Induced Stress Signaling and Inflammatory Responses in SKH-1 Mouse Skin by Topical Small-Molecule PD-L1 Blockade. JID innovations : skin science from molecules to population health, 4(2), 100255.
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  The immune checkpoint ligand PD-L1 has emerged as a molecular target for skin cancer therapy and might also hold promise for preventive intervention targeting solar UV light-induced skin damage. In this study, we have explored the role of PD-L1 in acute keratinocytic photodamage testing the effects of small-molecule pharmacological inhibition. Epidermal PD-L1 upregulation in response to chronic photodamage was established using immunohistochemical and proteomic analyses of a human skin cohort, consistent with earlier observations that PD-L1 is upregulated in cutaneous squamous cell carcinoma. Topical application of the small-molecule PD-L1 inhibitor BMS-202 significantly attenuated UV-induced activator protein-1 transcriptional activity in SKH-1 bioluminescent reporter mouse skin, also confirmed in human HaCaT reporter keratinocytes. RT-qPCR analysis revealed that BMS-202 antagonized UV induction of inflammatory gene expression. Likewise, UV-induced cleavage of procaspase-3, a hallmark of acute skin photodamage, was attenuated by topical BMS-202. NanoString nCounter transcriptomic analysis confirmed downregulation of cutaneous innate immunity- and inflammation-related responses, together with upregulation of immune response pathway gene expression. Further mechanistic analysis confirmed that BMS-202 antagonizes UV-induced PD-L1 expression both at the mRNA and protein levels in SKH-1 epidermis. These data suggest that topical pharmacological PD-L1 antagonism using BMS-202 shows promise for skin protection against photodamage.
• Diehl, K., Stoos, E., Becker, A., Orfaly, V. E., Nelson, J., Gillespie, J., Ng, J., Tobey, T., Latour, E., Ludzik, J., Berry, E. G., Geller, A. C., Jacobe, H., Leitenberger, J., McClanahan, D., Tran, J., Prasad, S., Mengden-Koon, S., Nelson, K. C., , Petering, R., et al. (2024). Melanoma toolkit for early detection for primary care clinicians: a 1-year follow-up on outcomes. Frontiers in medicine, 11, 1500216.
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  Primary care providers or clinicians (PCPs) have the potential to assist dermatologists in screening patients at risk for skin cancer, but require training to appropriately identify higher-risk patients, perform skin checks, recognize and biopsy concerning lesions, interpret pathology results, document the exam, and bill for the service. Very few validated dermatology training programs exist for PCPs and those that are available focus primarily on one emphasis area, which results in variable efficacy and single-topic limited scope.
• Fernandez, J. M., Koblinski, J. E., Dahak, S., Curiel-Lewandrowski, C., & Thiede, R. (2024). Gender differences in pediatric and adolescent melanoma: A retrospective analysis of 4645 cases. Journal of the American Academy of Dermatology, 90(2), 280-287.
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  There is paucity of data on how gender impacts melanoma prognosis in pediatric and adolescent patients.
• Scope, A., Liopyris, K., Weber, J., Barnhill, R. L., Braun, R. P., Curiel-Lewandrowski, C. N., Elder, D. E., Ferrara, G., Grant-Kels, J. M., Jeunon, T., Lallas, A., Lin, J. Y., Marchetti, M. A., Marghoob, A. A., Navarrete-Dechent, C., Pellacani, G., Soyer, H. P., Stratigos, A., Thomas, L., , Kittler, H., et al. (2024). International Skin Imaging Collaboration-Designated Diagnoses (ISIC-DX): Consensus terminology for lesion diagnostic labeling. Journal of the European Academy of Dermatology and Venereology : JEADV.
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  A common terminology for diagnosis is critically important for clinical communication, education, research and artificial intelligence. Prevailing lexicons are limited in fully representing skin neoplasms.
• Shafi, H., Lora, A. J., Donow, H. M., Dickinson, S. E., Wondrak, G. T., Chow, H. S., Curiel-Lewandrowski, C., & Mansour, H. M. (2024). Comprehensive Advanced Physicochemical Characterization and In Vitro Human Cell Culture Assessment of BMS-202: A Novel Inhibitor of Programmed Cell Death Ligand. Pharmaceutics, 16(11).
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  BMS-202, is a potent small molecule with demonstrated antitumor activity. The study aimed to comprehensively characterize the physical and chemical properties of BMS-202 and evaluate its suitability for topical formulation, focusing on uniformity, stability and safety profiles. A range of analytical techniques were employed to characterize BMS-202. Scanning Electron Microscopy (SEM) was used to assess morphology, Differential Scanning Calorimetry (DSC) provided insights of thermal behavior, and Hot-Stage Microscopy (HSM) corroborated these thermal behaviors. Molecular fingerprinting was conducted using Raman spectroscopy and Fourier Transform Infrared (FTIR) spectroscopy, with chemical uniformity of the batch further validated by mapping through FTIR and Raman microscopies. The residual water content was measured using Karl Fisher Coulometric titration, and vapor sorption isotherms examined moisture uptake across varying relative humidity levels. In vitro safety assessments involved testing with skin epithelial cell lines, such as HaCaT and NHEK, and Transepithelial Electrical Resistance (TEER) to evaluate barrier integrity. SEM revealed a distinctive needle-like morphology, while DSC indicated a sharp melting point at 110.90 ± 0.54 ℃ with a high enthalpy of 84.41 ± 0.38 J/g. HSM confirmed the crystalline-to-amorphous transition at the melting point. Raman and FTIR spectroscopy, alongside chemical imaging, confirmed chemical uniformity as well as validated the batch consistency. A residual water content of 2.76 ± 1.37 % (/) and minimal moisture uptake across relative humidity levels demonstrated its low hygroscopicity and suitability for topical formulations. Cytotoxicity testing showed dose-dependent reduction in skin epithelial cell viability at high concentrations (100 µM and 500 µM), with lower doses (0.1 µM to 10 µM) demonstrating acceptable safety. TEER studies indicated that BMS-202 does not disrupt the HaCaT cell barrier function. The findings from this study establish that BMS-202 has promising physicochemical and in vitro characteristics at therapeutic concentrations for topical applications, providing a foundation for future formulation development focused on skin-related cancers or localized immune modulation.
• Sugimura, M., Marcelino, K., Romero, R., Zhao, J., Kim, Y., Nessaee, A., Kim, K., Stratton, D., Curiel-Lewandrowski, C., Garfinkel, J., Rubinstein, G., & Kang, D. (2024). High-speed reflectance confocal microscopy using speckle modulation. Biomedical optics express, 15(8), 4877-4890.
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  We developed a spectrally-encoded, line reflectance confocal microscope (RCM) that uses a rotating diffuser to rapidly modulate the illumination speckle pattern. The speckle modulation approach reduced speckle noise while imaging with a spatially coherent light source needed for high imaging speed and cellular resolution. The speckle-modulation RCM device achieved lateral and axial resolutions of 1.1 µm and 2.8 µm, respectively. With an imaging speed of 107 frames/sec, three-dimensional RCM imaging over 300-µm depth was completed within less than 1 second. RCM images of human fingers, forearms, and oral mucosa clearly visualized the characteristic cellular features without any noticeable speckle noise.
• Eedara, B. B., Manivannan, B., Alabsi, W., Sun, B., Curiel-Lewandrowski, C., Zhang, T., Bode, A. M., & Mansour, H. M. (2023). Comprehensive Physicochemical Characterization, In Vitro Membrane Permeation, and In Vitro Human Skin Cell Culture of a Novel TOPK Inhibitor, HI-TOPK-032. International journal of molecular sciences, 24(21).
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  Nonmelanoma skin cancers (NMSC) are the most common skin cancers, and about 5.4 million people are diagnosed each year in the United States. A newly developed T-lymphokine-activated killer cell-originated protein kinase (TOPK) inhibitor, HI-TOPK-032, is effective in suppressing colon cancer cell growth, inducing the apoptosis of colon cancer cells and ultraviolet (UV) light-induced squamous cell carcinoma (SCC). This study aimed to investigate the physicochemical properties, permeation behavior, and cytotoxicity potential of HI-TOPK-032 prior to the development of a suitable topical formulation for targeted skin drug delivery. Techniques such as scanning electron microscopy (SEM), energy-dispersive X-ray (EDX) spectroscopy, differential scanning calorimetry (DSC), hot-stage microscopy (HSM), X-ray powder diffraction (XRPD), Karl Fisher (KF) coulometric titration, Raman spectrometry, confocal Raman microscopy (CRM), attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), and Fourier transform infrared microscopy were used to characterize HI-TOPK-032. The dose effect of HI-TOPK-032 on in vitro cell viability was evaluated using a 2D cell culture of the human skin keratinocyte cell line (HaCaT) and primary normal human epidermal keratinocytes (NHEKs). Transepithelial electrical resistance (TEER) at the air-liquid interface as a function of dose and time was measured on the HaCAT human skin cell line. The membrane permeation behavior of HI-TOPK-032 was tested using the Strat-M synthetic biomimetic membrane with an in vitro Franz cell diffusion system. The physicochemical evaluation results confirmed the amorphous nature of the drug and the homogeneity of the sample with all characteristic chemical peaks. The in vitro cell viability assay results confirmed 100% cell viability up to 10 µM of HI-TOPK-032. Further, a rapid, specific, precise, and validated reverse phase-high performance liquid chromatography (RP-HPLC) method for the quantitative estimation of HI-TOPK-032 was developed. This is the first systematic and comprehensive characterization of HI-TOPK-032 and a report of these findings.
• Kashani-Sabet, M., Leachman, S. A., Stein, J. A., Arbiser, J. L., Berry, E. G., Celebi, J. T., Curiel-Lewandrowski, C., Ferris, L. K., Grant-Kels, J. M., Grossman, D., Kulkarni, R. P., Marchetti, M. A., Nelson, K. C., Polsky, D., Seiverling, E. V., Swetter, S. M., Tsao, H., Verdieck-Devlaeminck, A., Wei, M. L., , Bar, A., et al. (2023). Early Detection and Prognostic Assessment of Cutaneous Melanoma: Consensus on Optimal Practice and the Role of Gene Expression Profile Testing. JAMA dermatology, 159(5), 545-553.
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  Therapy for advanced melanoma has transformed during the past decade, but early detection and prognostic assessment of cutaneous melanoma (CM) remain paramount goals. Best practices for screening and use of pigmented lesion evaluation tools and gene expression profile (GEP) testing in CM remain to be defined.
• LaFleur, B., Curiel-Lewandrowski, C., Tapia, E., Parker, J., White, L., Chow, H. S., & South, A. P. (2023). Characterizing dermal transcriptional change in the progression from sun-protected skin to actinic keratosis. The Journal of investigative dermatology.
• Romero, R., Zhao, J., Stratton, D., Marcelino, K., Sugimura, M., Nichols, A., Gonzalez, S., Jain, M., Curiel-Lewandrowski, C., & Kang, D. (2023). Handheld cross-polarised microscope for imaging individual pigmented cells in human skin in vivo. Journal of microscopy, 292(1), 47-55.
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  We present the development of a simple, handheld cross-polarised microscope (CPM) and demonstration of imaging individual pigmented cells in human skin in vivo. In the CPM device, the cross-polarised detection approach is used to reduce the specular reflection from the skin surface and preferentially detect multiply-scattered light. The multiply-scattered light works as back illumination from within the tissue towards the skin surface, and superficial pigment such as intraepidermal melanin absorbs some spectral bands of the multiply-scattered light and cast coloured shadows. Since the light that interacted with the superficial pigment only needs to travel a short distance before it exits the skin surface, microscopic details of the pigment can be preserved. The CPM device uses a water-immersion objective lens with a high numerical aperture to image the microscopic details with minimal spherical aberrations and a small depth of focus. Preliminary results from a pilot study of imaging skin lesions in vivo showed that the CPM device could reveal three-dimensional distribution of pigmented cells and intracellular distribution of pigment. Co-registered CPM and reflectance confocal microscopy images showed good correspondence between dark, brown cells in CPM images and bright, melanin-containing cells in reflectance confocal microscopy images.
• Ruiz, V. H., Encinas-Basurto, D., Sun, B., Eedara, B. B., Roh, E., Alarcon, N. O., Curiel-Lewandrowski, C., Bode, A. M., & Mansour, H. M. (2023). Innovative Rocuronium Bromide Topical Formulation for Targeted Skin Drug Delivery: Design, Comprehensive Characterization, In Vitro 2D/3D Human Cell Culture and Permeation. International journal of molecular sciences, 24(10).
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  Cutaneous squamous cell carcinoma (cSCC) is the second-most common type of non-melanoma skin cancer and is linked to long-term exposure to ultraviolet (UV) radiation from the sun. Rocuronium bromide (RocBr) is an FDA-approved drug that targets p53-related protein kinase (PRPK) that inhibits the development of UV-induced cSCC. This study aimed to investigate the physicochemical properties and in vitro behavior of RocBr. Techniques such as thermal analysis, electron microscopy, spectroscopy and in vitro assays were used to characterize RocBr. A topical oil/water emulsion lotion formulation of RocBr was successfully developed and evaluated. The in vitro permeation behavior of RocBr from its lotion formulation was quantified with Strat-M synthetic biomimetic membrane and EpiDerm™ 3D human skin tissue. Significant membrane retention of RocBr drug was evident and more retention was obtained with the lotion formulation compared with the solution. This is the first systematic and comprehensive study to report these findings.
• Bartlett, E. K., Grossman, D., Swetter, S. M., Leachman, S. A., Curiel-Lewandrowski, C., Dusza, S. W., Gershenwald, J. E., Kirkwood, J. M., Tin, A. L., Vickers, A. J., & Marchetti, M. A. (2022). Clinically Significant Risk Thresholds in the Management of Primary Cutaneous Melanoma: A Survey of Melanoma Experts. Annals of surgical oncology, 29(9), 5948-5956.
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  Risk-based thresholds to guide management are undefined in the treatment of primary cutaneous melanoma but are essential to advance the field from traditional stage-based treatment to more individualized care.
• Kelly, B. G., Stratton, D. B., Mansour, I., Tanriover, B., Culpepper, K. S., & Curiel-Lewandrowski, C. (2022). Navigating the initial diagnosis and management of adult IgA vasculitis: A review. JAAD international, 8, 71-78.
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  IgA vasculitis in adults has not been thoroughly studied. This has left a practice gap related to the management and follow-up of a population that is at an increased risk of comorbidities and potentially poor outcomes. For this reason, it is important to synthesize evidence from the current literature because this can help direct the movement for more robust studies to clarify best practice recommendations.
• Mesgarzadeh, S., Myrdal, C., Stratton, D., & Curiel-Lewandrowski, C. (2022). Intralesional Bleomycin Combined With Cryotherapy in the Treatment of Recalcitrant Verruca Vulgaris. Journal of drugs in dermatology : JDD, 21(2), 195-196.
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  Verruca vulgaris is a common cutaneous manifestation of Human Papillomavirus (HPV) infection that presents as hyperkeratotic, cauliflower-like papules with central black petechiae. These lesions may be resistant to conventional therapies, posing a therapeutic challenge and prolong significant morbidity for the patient. This case report demonstrates an immediate and robust response of recalcitrant warts to intralesional bleomycin injection paired with cryotherapy. J Drugs Dermatol. 2022;21(2):195-196. doi:10.36849/JDD.6424.
• Myrdal, C. N., Mehta, P. P., & Curiel-Lewandrowski, C. (2022). Dermatologists and the Aging Eye: Visual Performance in Physicians. Cutis, 110(2), E26-E27.
• Ruiz, V. H., Encinas-Basurto, D., Sun, B., Eedara, B. B., Dickinson, S. E., Wondrak, G. T., Chow, H. -., Curiel-Lewandrowski, C., & Mansour, H. M. (2022). Design, Physicochemical Characterization, and In Vitro Permeation of Innovative Resatorvid Topical Formulations for Targeted Skin Drug Delivery. Pharmaceutics, 14(4).
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  Nonmelanoma skin cancers (NMSCs) are the most common malignancies worldwide and affect more than 5 million people in the United States every year. NMSC is directly linked to the excessive exposure of the skin to solar ultraviolet (UV) rays. The toll-like receptor 4 (TLR4) antagonist, resatorvid (TAK-242), is a novel prototype chemo preventive agent that suppresses the production of inflammation mediators induced by UV exposure. This study aimed to design and develop TAK-242 into topical formulations using FDA-approved excipients, including DermaBase, PENcream, polyethylene glycol (PEG)-400, propylene glycol (PG), carbomer gel, hyaluronic acid (HA) gel, and Pluronic F-127 poloxamer triblock copolymer gel for the prevention of skin cancer. The physicochemical properties of raw TAK-242, which influence the compatibility and solubility in the selected base materials, were confirmed using X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), hot-stage microscopy (HSM), Raman spectroscopy, and attenuated total reflectance Fourier-transform infrared (ATR-FTIR) spectroscopic analysis. The permeation behavior of TAK-242 from the prepared formulations was determined using Strat-M transdermal diffusion membranes, and 3D cultured primary human-derived epidermal keratinocytes (EpiDerm). Despite TAK-242's high molecular weight and hydrophobicity, it can permeate through reconstructed human epidermis from all formulations. The findings, reported for the first time in this study, emphasize the capabilities of the topical application of TAK-242 via these multiple innovative topical drug delivery formulation platforms.
• Sun, M. D., Kentley, J., Wilson, B. W., Soyer, H. P., Curiel-Lewandrowski, C. N., Rotemberg, V. M., Halpern, A. C., & , I. T. (2022). Digital skin imaging applications, part II: a comprehensive survey of post-acquisition image utilization features and technology standards. Skin research and technology : official journal of International Society for Bioengineering and the Skin (ISBS) [and] International Society for Digital Imaging of Skin (ISDIS) [and] International Society for Skin Imaging (ISSI), 28(6), 771-779.
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  Despite the increasing ubiquity and accessibility of teledermatology applications, few studies have comprehensively surveyed their features and technical standards. Importantly, features implemented after the point of capture are often intended to augment image utilization, while technical standards affect interoperability with existing healthcare systems. We aim to comprehensively survey image utilization features and technical characteristics found within publicly discoverable digital skin imaging applications.
• Sun, M. D., Kentley, J., Wilson, B. W., Soyer, H. P., Curiel-Lewandrowski, C. N., Rotemberg, V., Halpern, A. C., & , I. T. (2022). Digital skin imaging applications, part I: Assessment of image acquisition technique features. Skin research and technology : official journal of International Society for Bioengineering and the Skin (ISBS) [and] International Society for Digital Imaging of Skin (ISDIS) [and] International Society for Skin Imaging (ISSI), 28(4), 623-632.
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  The rapid adoption of digital skin imaging applications has increased the utilization of smartphone-acquired images in dermatology. While this has enormous potential for scaling the assessment of concerning skin lesions, the insufficient quality of many consumer/patient-taken images can undermine clinical accuracy and potentially harm patients due to lack of diagnostic interpretability. We aim to characterize the current state of digital skin imaging applications and comprehensively assess how image acquisition features address image quality.
• Sundararajan, S., Arif Tiwari, H., Stratton, D., Curiel, C. N., Cui, H., & Roe, D. (2022). A single arm phase 2 study of talimogene laherparepvec in patients with low-risk invasive cutaneous squamous cell cancer. interim analysis.. Journal of Clinical Oncology, 40(16_suppl), e21583-e21583. doi:10.1200/jco.2022.40.16_suppl.e21583
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  e21583 Background: A compromised immune-surveillance plays an important role in the pathogenesis of cutaneous squamous cell carcinoma (cSCC). Talimogene laherparepvec (TVEC) is an HSV-1 oncolytic immunological agent FDA approved for the local treatment of unresectable recurrent melanoma. It is proposed that T-VEC directly destroys cancer cells, and induces production of GM-CSF to enhance systemic antitumor immune recognition. This proposed mechanism of action supports the innovative approach to implement TVEC in the management of cSCC. Methods: Immunocompetent patients > 18 years of age and diagnosed with at least one > 0.5 cm to < 5.0 cm, primary and histologically confirmed well-moderate differentiated cSCC, without evidence of perineural or vascular invasion were eligible to participate. Unresectable lesions or patients unable/unwilling to undergo standard of care treatment were eligible to participate. Study lesions include target injected lesions (TILs) and target non-injected lesions (TNILs). A total of up to 5 TILs were selected per subject. If feasible, target non-injected lesions (TNILs) were also selected in eligible participants to evaluate for abscopal effect. Every TIL was injected up to 4 times based lesion diameter according to current TVEC approved protocol administration and followed for 1yr after the 1 st injection. The primary endpoint of the study was to evaluate the overall response rate (ORR), defined as the proportion of subjects who achieved complete response (CR) and partial response (PR) in the TILs. Safety and adverse effect profile (AEs), duration of ORR, time to response (TTR), durable response rate, and time to progression, were the secondary endpoints included. A Simon 2 stage design was used. Total sample size was calculated to be 20 subjects. Seven subjects were recruited for stage 1 with a plan to recruit an additional 13 patients if five or more subjects met the primary endpoint in stage 1. Results: The interim analysis was conducted after the 7th participant completed Visit 8 (352-266 days from study initiation). For the primary endpoint, all 7 participants achieved an overall complete response (100%; 95% CI: 59.0-100%). NCI CTCAE (v. 4.0) was used to assess the safety and adverse effect profile. All AEs ranged from grades 1-2, and most commonly experienced transient fatigue (n = 3/7), flu like symptoms (n = 2/7) and headaches (n = 2/7). The mean time to response was 43.4 (SD 31.6) days and for duration of ORR 190.0 days (SD 39.3) at the time of analysis. The 2 TNILs evaluated in the interim analysis also demonstrated 100% CR (95% CI: 15.8-100%). Conclusions: TVEC showed extremely impressive ORR for patients with cSCC with a 100% CR in stage 1 of our pilot study. AE profile of TVEC was mild and was well tolerated. Completion of the study will further assess this high response rate. Clinical trial information: 03714828.
• Trepanowski, N., Chang, M. S., Zhou, G., Ahmad, M., Berry, E. G., Bui, K., Butler, W. H., Chu, E. Y., Curiel-Lewandrowski, C., Dellalana, L. E., Ellis, D. L., Freeman, S. C., Gorrepati, P. L., Grossman, D., Gyurdzhyan, S., Kanetsky, P. A., King, A. L., Kolla, A. M., Lian, C. G., , Lin, J. Y., et al. (2022). Delays in melanoma presentation during the COVID-19 pandemic: A nationwide multi-institutional cohort study. Journal of the American Academy of Dermatology, 87(5), 1217-1219.
• Atkins, M. B., Curiel-Lewandrowski, C., Fisher, D. E., Swetter, S. M., Tsao, H., Aguirre-Ghiso, J. A., Soengas, M. S., Weeraratna, A. T., Flaherty, K. T., Herlyn, M., Sosman, J. A., Tawbi, H. A., Pavlick, A. C., Cassidy, P. B., Chandra, S., Chapman, P. B., Daud, A., Eroglu, Z., Ferris, L. K., , Fox, B. A., et al. (2021). The State of Melanoma: Emergent Challenges and Opportunities. Clinical cancer research : an official journal of the American Association for Cancer Research.
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  Five years ago, the Melanoma Research Foundation (MRF) conducted an assessment of the challenges and opportunities facing the melanoma research community and patients with melanoma. Since then, remarkable progress has been made on both the basic and clinical research fronts. However, the incidence, recurrence and death rates for melanoma remain unacceptably high and significant challenges remain. Hence, the MRF Scientific Advisory Council and Breakthrough Consortium, a group that includes clinicians and scientists, reconvened to facilitate intensive discussions on thematic areas essential to melanoma researchers and patients alike - prevention, detection, diagnosis, metastatic dormancy and progression, response and resistance to targeted and immune-based therapy, and the clinical consequences of COVID-19 for melanoma patients and providers. These extensive discussions helped to crystalize our understanding of the challenges and opportunities facing the broader melanoma community today. In this report, we discuss the progress made since the last MRF assessment, comment on what remains to be overcome and offer recommendations for the best path forward.
• Borden, E. S., Adams, A. C., Buetow, K. H., Wilson, M. A., Bauman, J. E., Curiel-Lewandrowski, C., Chow, H. S., LaFleur, B. J., & Hastings, K. T. (2021). Shared Gene Expression and Immune Pathway Changes Associated with Progression from Nevi to Melanoma. Cancers, 14(1).
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  There is a need to identify molecular biomarkers of melanoma progression to assist the development of chemoprevention strategies to lower melanoma incidence. Using datasets containing gene expression for dysplastic nevi and melanoma or melanoma arising in a nevus, we performed differential gene expression analysis and regularized regression models to identify genes and pathways that were associated with progression from nevi to melanoma. A small number of genes distinguished nevi from melanoma. Differential expression of seven genes was identified between nevi and melanoma in three independent datasets. C1QB, CXCL9, CXCL10, DFNA5 (GSDME), FCGR1B, and PRAME were increased in melanoma, and SCGB1D2 was decreased in melanoma, compared to dysplastic nevi or nevi that progressed to melanoma. Further supporting an association with melanomagenesis, these genes demonstrated a linear change in expression from benign nevi to dysplastic nevi to radial growth phase melanoma to vertical growth phase melanoma. The genes associated with melanoma progression showed significant enrichment of multiple pathways related to the immune system. This study demonstrates (1) a novel application of bioinformatic approaches to aid clinical trials of melanoma chemoprevention and (2) the feasibility of determining a gene signature biomarker of melanomagenesis.
• Chang, M. S., Leachman, S. A., Berry, E. G., Curiel-Lewandrowski, C., Geller, A. C., Grossman, D., Kim, C. C., Stein, J. A., Swetter, S. M., & Hartman, R. I. (2021). Changes in melanoma care practices during the COVID-19 pandemic: a multi-institutional cross-sectional survey. Dermatology online journal, 27(4).
• Curiel-Lewandrowski, C., Myrdal, C. N., Saboda, K., Hu, C., Arzberger, E., Pellacani, G., Legat, F. J., Ulrich, M., Hochfellner, P., Oliviero, M. C., Pasquali, P., Gill, M., & Hofmann-Wellenhof, R. (2021). In Vivo Reflectance Confocal Microscopy as a Response Monitoring Tool for Actinic Keratoses Undergoing Cryotherapy and Photodynamic Therapy. Cancers, 13(21).
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  Reflectance confocal microscopy (RCM) presents a non-invasive method to image actinic keratosis (AK) at a cellular level. However, RCM criteria for AK response monitoring vary across studies and a universal, standardized approach is lacking. We aimed to identify reliable AK response criteria and to compare the clinical and RCM evaluation of responses across AK severity grades. Twenty patients were included and randomized to receive either cryotherapy ( = 10) or PDT ( = 10). Clinical assessment and RCM evaluation of 12 criteria were performed in AK lesions and photodamaged skin at baseline, 3 and 6 months. We identified the RCM criteria that reliably characterize AK at baseline and display significant reduction following treatment. Those with the highest baseline odds ratio (OR), good interobserver agreement, and most significant change over time were atypical honeycomb pattern (OR: 12.7, CI: 5.7-28.1), hyperkeratosis (OR: 13.6, CI: 5.3-34.9), stratum corneum disruption (OR: 7.8, CI: 3.5-17.3), and disarranged epidermal pattern (OR: 6.5, CI: 2.9-14.8). Clinical evaluation demonstrated a significant treatment response without relapse. However, in grade 2 AK, 10/12 RCM parameters increased from 3 to 6 months, which suggested early subclinical recurrence detection by RCM. Incorporating standardized RCM protocols for the assessment of AK may enable a more meaningful comparison across clinical trials, while allowing for the early detection of relapses and evaluation of biological responses to therapy over time.
• Dickinson, S. E., Khawam, M., Kirschnerova, V., Vaishampayan, P., Centuori, S. M., Saboda, K., Calvert, V. S., Petricoin, E. F., & Curiel-Lewandrowski, C. (2021). Increased PD-L1 Expression in Human Skin Acutely and Chronically Exposed to UV Irradiation. Photochemistry and photobiology.
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  Overexpression of PD-L1 (CD274) on tumor cells may represent a hallmark of immune evasion, and overexpression has been documented in several tumors including cutaneous squamous cell carcinoma (cSCC). While PD-L1/PD-1 activity in the skin has been primarily described in inflammatory models, our goal was to examine PD-L1 expression in human keratinocytes exposed to UV irradiation. We assessed PD-L1 expression in human sun-protected (SP) and sun-damaged (SD) skin, actinic keratosis (AK), and cSCC using IHC and protein microarray. Both methods found low baseline levels of PD-L1 in SP and SD skin and significantly increased expression in cSCC. Next, we examined PD-L1 expression in acute models of UV exposure. In human SP skin exposed to 2-3 MED of UV (n = 20), epidermal PD-L1 was induced in 70% of subjects after 24 h (P = 0.0001). SKH-1 mice exposed to acute UV also showed significant epidermal PD-L1 induction at 16, 24 and 48 h. A time- and dose-dependent induction of PD-L1 was confirmed in cultured human keratinocytes after UV, which was markedly reduced in the presence of MEK/ERK, JNK or STAT3 inhibitors. These findings suggest that UV induces upregulation of PD-L1 through established, pharmacologically targetable stress-signaling pathways in keratinocytes.
• Dickinson, S. E., Wondrak, G. T., Vaishampayan, P., Kirschnerova, V., Khawam, M., & Curiel-lewandrowski, C. (2021). Abstract 2447: TLR4 expression as a determinant of EMT and stress response gene expression in UV exposed human keratinocytes. Cancer Research, 81(13_Supplement), 2447-2447. doi:10.1158/1538-7445.am2021-2447
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  Abstract Toll-like receptor 4 (TLR4) is gaining attention for its role in several cancer-associated signaling pathways, including the regulation of inflammation, DNA repair and epithelial-mesenchymal transition (EMT). There is evidence that TLR4 contributes to ultraviolet (UV) radiation-induced stress signaling in skin cells, including keratinocytes. Blockade of TLR4 activity using the pharmacological antagonist resatorvid (TAK-242) inhibits not only acute UV-induced signaling in vitro and in vivo, but blocks UV-induced skin carcinogenesis in mouse models. In order to genetically explore the role of TLR4 in keratinocyte responses to UV-induced stress, we recently utilized CRISPR/Cas9 techniques to delete TLR4 from the genome of human HaCaT keratinocyte cells in culture. First, using differential gene expression analysis (employing the EMTRT2 Profiler PCR array technology) it was observed that TLR4 KO status is associated with pronounced downregulation of EMT-related gene expression (MMP9, VIM, FN1, SNAI1, TWIST1) confirmed by independent RT-qPCR analysis. TLR4 was also a determinant of UV-induced inflammatory enzyme expression including PTGS2. Phenotypically, TLR4 KO cells displayed an attenuation of Matrigel transwell migration. TLR4 KO cells demonstrated increased sensitivity to UV-induced apoptosis as detected by flow cytometry of annexin V/propidium iodide stained cells, and by immunodetection of increased PARP cleavage. Moreover, NanoString nCounter expression analysis of murine skin chronically exposed to tumorigenic UV indicated that topical resatorvid treatment was associated with MMP9 downregulation. Future studies will employ this novel TLR4 KO keratinocyte cell line as a mechanistic tool to dissect the role of TLR4 in inflammatory signaling and EMT response in the context of skin photodamage and carcinogenesis. Supported by NIH grants ES029579, R03CA230830, P01CA229112. Citation Format: Viktoria Kirschnerova, Prajakta Vaishampayan, Maria Khawam, Clara Curiel-Lewandrowski, Georg T. Wondrak, Sally E. Dickinson. TLR4 expression as a determinant of EMT and stress response gene expression in UV exposed human keratinocytes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2447.
• Fazel, M., AlRawashdh, N., Alamer, A., Curiel-Lewandrowski, C., & Abraham, I. (2021). Is there still a role for talimogene laherparepvec (T-VEC) in advanced melanoma? An indirect efficacy comparison of T-VEC plus ipilimumab combination therapy versus T-VEC alone as salvage therapy in unresectable metastatic melanoma. Expert opinion on biological therapy, 21(12), 1647-1653.
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  Talimogene laherparepvec (T-VEC) improves overall survival (OS) in unresectable stage IIIB/C-IV melanoma T-VEC may have synergistic effects with CTLA-4 inhibitors In the absence of a trial comparing T-VEC and ipilimumab (T-VEC + IPI) to T-VEC, we applied a novel indirect comparison method using extrapolated OS curves to estimate OS outcomes in a simulated trial comparing both regimens in stage IIIB/C-IV unresectable melanoma.
• Fried, L. J., Tan, A., Berry, E. G., Braun, R. P., Curiel-Lewandrowski, C., Curtis, J., Ferris, L. K., Hartman, R. I., Jaimes, N., Kawaoka, J. C., Kim, C. C., Lallas, A., Leachman, S. A., Levin, A., Lucey, P., Marchetti, M. A., Marghoob, A. A., Miller, D., Nelson, K. C., , Prodanovic, E., et al. (2021). Dermoscopy Proficiency Expectations for US Dermatology Resident Physicians: Results of a Modified Delphi Survey of Pigmented Lesion Experts. JAMA dermatology.
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  Dermoscopy education in US dermatology residency programs varies widely, and there is currently no existing expert consensus identifying what is most important for resident physicians to know.
• Koh, U., Betz-Stablein, B., O'Hara, M., Horsham, C., Curiel-Lewandrowski, C., Soyer, H. P., & Janda, M. (2021). Development of a Checklist Tool to Assess the Quality of Skin Lesion Images Acquired by Consumers Using Sequential Mobile Teledermoscopy. Dermatology (Basel, Switzerland), 1-8.
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  Mobile teledermoscopy is an emerging technology that involves imaging and digitally sending dermoscopic images of skin lesions to a clinician for assessment. High-quality, consistent images are required for accurate telediagnoses when monitoring lesions over time. To date there are no tools to assess the quality of sequential images taken by consumers using mobile teledermoscopy. The purpose of this study was to develop a tool to assess the quality of images acquired by consumers.
• Myrdal, C. N., Mesgarzadeh, S., Loh, T. Y., Culpepper, K. S., & Curiel-Lewandrowski, C. (2021). Coalescing plaques on the face, trunk, and upper extremities. JAAD case reports, 16, 158-160.
• Myrdal, C. N., Stratton, D. B., Davis, T. L., & Curiel-Lewandrowski, C. (2021). Generalised eruptive histiocytosis preceded by systemic symptoms. BMJ case reports, 14(6).
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  Generalised eruptive histiocytosis is a rare proliferative disease that typically presents with indolent cutaneous eruptions. We describe the case of a 73-year-old man presenting with diffuse, asymptomatic crops of pink to dusky red papules preceded by general malaise, myalgias, fluctuating fever, chills, and weight loss. Histological evaluation revealed a non-Langerhans cell histiocytic dermal infiltrate with spindle cell features and chronic inflammation, reactive for CD68 and negative for both S100 and CD1a. Malignancy screening was negative. This report aims to highlight a unique presentation of generalised eruptive histiocytosis, emphasise histological findings, and discuss considerations for malignancy screening.
• Myrdal, C. N., Sundararajan, S., & Curiel-Lewandrowski, C. (2021). Widespread Hypertrophic Lichen Planus following Programmed Cell Death Ligand 1 Blockade. Case reports in dermatology, 12(2), 119-123.
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  Hypertrophic lichen planus (HLP) may not have the typical histological findings of lichen planus and often mimics squamous cell carcinoma (SCC). Distinguishing between the two can pose a diagnostic challenge. Here, we present a case of eruptive HLP mimicking SCC in the context of programmed cell death ligand 1 (PD-L1) immune checkpoint inhibition. A 73-year-old woman recently treated with durvalumab, an anti-PD-L1 antibody, presented to our clinic with diffuse hyperkeratotic papules and plaques previously thought to be eruptive SCC. The lesions did not respond to topical fluorouracil and continued to appear despite discontinuation of immunotherapy. Further histological analysis revealed intraepidermal epithelial proliferation with lichenoid inflammation. Subsequent treatment with topical corticosteroids significantly improved the size and number of lesions. The diagnosis of HLP was made based on histological features and response to topical steroids in the context of recent immunotherapy. This case reveals HLP as a potential adverse effect of PD-L1 inhibition and highlights the need for additional diagnostic assessment in patients presenting with eruptive hyperkeratotic lesions, especially on the lower extremities.
• Smith, E., Curiel-lewandrowski, C., Sundararajan, S., Myrdal, C. N., Mehta, P., Mcbride, A., Curiel-lewandrowski, C., Briones, K., & Albright, J. (2021). Incidence of immune-related adverse events with pembrolizumab in advanced melanoma and correlation with treatment response: A single institution review of irAEs.. Journal of Clinical Oncology, 39(15_suppl), e21519-e21519. doi:10.1200/jco.2021.39.15_suppl.e21519
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  e21519 Background: Anti-PD-1 therapy has become a mainstay of advanced melanoma treatment. However, associated irAEs are common and contribute to significant delays or cessation of treatment. In this retrospective cohort study, we aim to characterize the real-world irAE profile of pembrolizumab at our institution and its prognostic implications. Methods: We evaluated unresectable stage III-IV melanoma patients treated with pembrolizumab between 2011 and 2016 at the University of Arizona Cancer Center (UACC). Information regarding demographics, treatment, irAEs, and hospitalizations were recorded. Adverse events were graded using the common terminology criteria for adverse events v.4.0 (CTCAE). Results: Seventy-three patients were identified, 4 (5.5%) with unresectable stage III and 69 (94.5%) with stage IV melanoma. The median age was 68; 48 (65.8%) patients were male and 25 (34.2%) were female. Nineteen patients (26.0%) had a preexisting autoimmune disorder. 171 irAEs were identified in 58 of the patients. 141 (82.5%) were Grade 1, 24 (14.0%) were Grade 2, and 6 (3.5%) were Grade 3. Incidence and time to onset of significant events is displayed in Table. Eleven (15%) patients were hospitalized, and 8 patients (11.0%) stopped treatment due to an irAE. Sixteen (84.2%) patients with a preexisting autoimmune condition experienced an irAE versus 78% of patients without an autoimmune condition. Twelve patients (75%) had an exacerbation of their autoimmune condition. Response could be assessed in 67 patients . 30 patients of the 67 (45%) had a CR or a PR and 37 patients (55%) had progressive disease (PD). 58 of 67 (87%) experienced an irAE. 29 (50%) of the 58 irAE patients had PD, while 8 (88.9%) of the 9 non-irAE patients had PD. The relative risk of progression in patients who experienced an irAE versus who did not was 0.56 (95% CI: 0.39-0.79, p= 0.001). Conclusions: Experience with pembrolizumab at our institution suggests a similar irAE profile compared to landmark trials, though we observed a higher percentage of patients who required discontinuation of pembrolizumab (11% versus 5% in Phase III trials). In our retrospective study, the risk for progression was significantly higher in patients without irAE versus with any irAE, suggesting that development of irAE could be a positive prognostic sign.[Table: see text]
• Waldman, R. A., Swetter, S. M., Stein, J. A., Scope, A., Rodriguez, S. G., Rao, B., Rabinovitz, H. S., Pellacani, G., Markowitz, O., Marghoob, A. A., Kerr, P., Hu, S., Grant-kels, J. M., Curtis, J. A., & Curiel, C. N. (2021). Consensus recommendations for the use of noninvasive melanoma detection techniques based on results of an international Delphi process.. Journal of the American Academy of Dermatology, 85(3), 745-749. doi:10.1016/j.jaad.2019.09.046
• Yozwiak, M., Stratton, S. P., Saboda, K., Myrdal, C. N., Krase, I. Z., Gill, M., & Curiel-lewandrowski, C. (2021). 671 Morphological and histological effect of emollient application in actinic keratoses. Journal of Investigative Dermatology, 141(5). doi:10.1016/j.jid.2021.02.701
• Zhao, J., Jain, M., Harris, U. G., Kose, K., Curiel-Lewandrowski, C., & Kang, D. (2021). Deep Learning-Based Denoising in High-Speed Portable Reflectance Confocal Microscopy. Lasers in surgery and medicine.
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  Portable confocal microscopy (PCM) is a low-cost reflectance confocal microscopy technique that can visualize cellular details of human skin in vivo. When PCM images are acquired with a short exposure time to reduce motion blur and enable real-time 3D imaging, the signal-to-noise ratio (SNR) is decreased significantly, which poses challenges in reliably analyzing cellular features. In this paper, we evaluated deep learning (DL)-based approach for reducing noise in PCM images acquired with a short exposure time.
• Curiel-Lewandrowski, C. (2020). Widespread Hypertrophic Lichen Planus following Programmed Cell Death Ligand 1 Blockade.. Case Rep Dermatol., 12(2), 119–123.
• Curiel-Lewandrowski, C., Stratton, D. B., Gong, C., & Kang, D. (2020). Preliminary imaging of skin lesions with near-infrared, portable confocal microscopy. Journal of the American Academy of Dermatology.
• Gong, C., Stratton, D. B., Curiel-Lewandrowski, C. N., & Kang, D. (2020). Speckle-free, near-infrared portable confocal microscope. Applied optics, 59(22), G41-G46.
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  We have developed a portable confocal microscope (PCM) that uses an inexpensive near-infrared LED as the light source. Use of the spatially incoherent light source significantly reduced the speckle contrast. The PCM device was manufactured at the material cost of approximately 5000 and weighed only 1 kg. Lateral and axial resolutions were measured as 1.6 and 6.0 µm, respectively. Preliminary in vivo skin imaging experiment results showed that the PCM device could visualize characteristic cellular features of human skin extending from the stratum corneum to the superficial dermis. Dynamic imaging of blood flow in vivo was also demonstrated. The capability to visualize cellular features up to the superficial dermis is expected to facilitate evaluation and clinical adoption of this low-cost diagnostic imaging tool.
• Grossman, D., Okwundu, N., Bartlett, E. K., Marchetti, M. A., Othus, M., Coit, D. G., Hartman, R. I., Leachman, S. A., Berry, E. G., Korde, L., Lee, S. J., Bar-Eli, M., Berwick, M., Bowles, T., Buchbinder, E. I., Burton, E. M., Chu, E. Y., Curiel-Lewandrowski, C., Curtis, J. A., , Daud, A., et al. (2020). Prognostic Gene Expression Profiling in Cutaneous Melanoma: Identifying the Knowledge Gaps and Assessing the Clinical Benefit. JAMA dermatology, 156(9), 1004-1011.
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  Use of prognostic gene expression profile (GEP) testing in cutaneous melanoma (CM) is rising despite a lack of endorsement as standard of care.
• Janda, M., Horsham, C., Koh, U., Gillespie, N., Vagenas, D., Loescher, L. J., Curiel-Lewandrowski, C., Hofmann-Wellenhof, R., & Peter Soyer, H. (2020). Evaluating healthcare practitioners' views on store-and-forward teledermoscopy services for the diagnosis of skin cancer. Digital health, 5, 2055207619828225.
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  The aim of the study is to evaluate healthcare practitioners' views on and satisfaction with (i) digital image acquisition and storage and (ii) store-and-forward teledermoscopy services for the diagnosis of skin cancer in their clinical practice.
• Janda, M., Horsham, C., Vagenas, D., Loescher, L. J., Gillespie, N., Koh, U., Curiel-Lewandrowski, C., Hofmann-Wellenhof, R., Halpern, A., Whiteman, D. C., Whitty, J. A., Smithers, B. M., & Soyer, H. P. (2020). Accuracy of mobile digital teledermoscopy for skin self-examinations in adults at high risk of skin cancer: an open-label, randomised controlled trial. The Lancet. Digital health, 2(3), e129-e137.
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  Skin self-examinations supplemented with mobile teledermoscopy might improve early detection of skin cancers compared with naked-eye skin self-examinations. We aimed to assess whether mobile teledermoscopy-enhanced skin self-examination can improve sensitivity and specificity of self-detection of skin cancers when compared with naked-eye skin self-examination.
• Jedlowski, P. M., Fazel, M., Foshee, J. P., & Curiel-Lewandrowski, C. (2020). A patient with concurrent prurigo nodularis and squamous cell carcinomas of keratoacanthoma type: The role of aprepitant in diagnostic clarity. JAAD case reports, 6(1), 3-5.
• Marchetti, M. A., Liopyris, K., Dusza, S. W., Codella, N. C., Gutman, D. A., Gutman, D. A., Helba, B., Kalloo, A., Halpern, A. C., Curiel-lewandrowski, C., Soyer, H. P., Malvehy, J., Curiel-lewandrowski, C., & Caffery, L. J. (2020). Computer algorithms show potential for improving dermatologists' accuracy to diagnose cutaneous melanoma: Results of the International Skin Imaging Collaboration 2017.. Journal of the American Academy of Dermatology, 82(3), 622-627. doi:10.1016/j.jaad.2019.07.016
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  Computer vision has promise in image-based cutaneous melanoma diagnosis but clinical utility is uncertain..To determine if computer algorithms from an international melanoma detection challenge can improve dermatologists' accuracy in diagnosing melanoma..In this cross-sectional study, we used 150 dermoscopy images (50 melanomas, 50 nevi, 50 seborrheic keratoses) from the test dataset of a melanoma detection challenge, along with algorithm results from 23 teams. Eight dermatologists and 9 dermatology residents classified dermoscopic lesion images in an online reader study and provided their confidence level..The top-ranked computer algorithm had an area under the receiver operating characteristic curve of 0.87, which was higher than that of the dermatologists (0.74) and residents (0.66) (P < .001 for all comparisons). At the dermatologists' overall sensitivity in classification of 76.0%, the algorithm had a superior specificity (85.0% vs. 72.6%, P = .001). Imputation of computer algorithm classifications into dermatologist evaluations with low confidence ratings (26.6% of evaluations) increased dermatologist sensitivity from 76.0% to 80.8% and specificity from 72.6% to 72.8%..Artificial study setting lacking the full spectrum of skin lesions as well as clinical metadata..Accumulating evidence suggests that deep neural networks can classify skin images of melanoma and its benign mimickers with high accuracy and potentially improve human performance.
• Navarrete-Dechent, C., Liopyris, K., Molenda, M. A., Braun, R., Curiel-Lewandrowski, C., Dusza, S. W., Guitera, P., Hofmann-Wellenhof, R., Kittler, H., Lallas, A., Malvehy, J., Marchetti, M. A., Oliviero, M., Pellacani, G., Puig, S., Soyer, H. P., Tejasvi, T., Thomas, L., Tschandl, P., , Scope, A., et al. (2020). Human surface anatomy terminology for dermatology: a Delphi consensus from the International Skin Imaging Collaboration. Journal of the European Academy of Dermatology and Venereology : JEADV, 34(11), 2659-2663.
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  There is no internationally vetted set of anatomic terms to describe human surface anatomy.
• Nguyen, T. N., Rajapakshe, K., Nicholas, C., Tordesillas, L., Ehli, E. A., Davis, C. M., Coarfa, C., Flores, E. R., Dickinson, S. E., Curiel-Lewandrowski, C., & Tsai, K. Y. (2020). Integrative transcriptomic analysis for linking acute stress responses to squamous cell carcinoma development. Scientific reports, 10(1), 17209.
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  Cutaneous squamous cell carcinoma (cuSCC) is the second most common skin cancer and commonly arises in chronically UV-exposed skin or chronic wounds. Since UV exposure and chronic wounds are the two most prominent environmental factors that lead to cuSCC initiation, we undertook this study to test whether more acute molecular responses to UV and wounding overlapped with molecular signatures of cuSCC. We reasoned that transcriptional signatures in common between acutely UV-exposed skin, wounded skin, and cuSCC tumors, might enable us to identify important pathways contributing to cuSCC. We performed transcriptomic analysis on acutely UV-exposed human skin and integrated those findings with datasets from wounded skin and our transcriptomic data on cuSCC using functional pair analysis, GSEA, and pathway analysis. Integrated analyses revealed significant overlap between these three datasets, thus highlighting deep molecular similarities these biological processes, and we identified Oncostatin M (OSM) as a potential common upstream driver. Expression of OSM and its downstream targets correlated with poorer overall survival in head and neck SCC patients. In vitro, OSM promoted invasiveness of keratinocytes and cuSCC cells and suppressed apoptosis of irradiated keratinocytes. Together, these results support the concept of using an integrated, biologically-informed approach to identify potential promoters of tumorigenesis.
• Price, K. N., Thiede, R., Shi, V. Y., & Curiel-Lewandrowski, C. (2020). Strategic dermatology clinical operations during the coronavirus disease 2019 (COVID-19) pandemic. Journal of the American Academy of Dermatology, 82(6), e207-e209.
• Roh, E., Han, Y., Reddy, K., Zykova, T. A., Lee, M. H., Yao, K., Bai, R., Curiel-Lewandrowski, C., & Dong, Z. (2020). Suppression of the solar ultraviolet-induced skin carcinogenesis by TOPK inhibitor HI-TOPK-032. Oncogene, 39(21), 4170-4182.
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  Nonmelanoma skin cancer (NMSC) such as cutaneous squamous cell carcinoma (cSCC) is caused by solar ultraviolet (SUV) exposure and is the most common cancer in the United States. T-LAK cell-originated protein kinase (TOPK), a serine-threonine kinase is activated by SUV irradiation and involved in skin carcinogenesis. Strategies with research focusing on the TOPK signaling pathway and targeted therapy in skin carcinogenesis may helpful for the discovery of additional treatments against skin cancer. In this study, we found that TOPK can directly bind to and phosphorylate c-Jun (as one of the core member of AP-1) at Ser63 and Ser73 after SSL exposure in a JNKs-independent manner. TOPK knocking down, or HI-TOPK-032 (TOPK specific inhibitor) attenuated colony formation and cell proliferation of skin cancer cells. Phosphorylated levels of c-Jun were overexpressed in human AK and cSCC compared with normal skin tissues, and HI-TOPK-032 inhibited the phosphorylation of c-Jun in SCC cell line in a dose-dependent manner. Furthermore, HI-TOPK-032 decreased SSL-induced AP-1 transactivation activity. Moreover, acute SSL-induced inflammation was attenuated by the topical application of HI-TOPK-032 in SKH1 hairless mice. Importantly, HI-TOPK-032 suppressed chronic SSL-induced skin carcinogenesis and c-Jun phosphorylation levels in SKH1 hairless mice. Our results demonstrate that TOPK can phosphorylate and activate c-Jun at Ser63 and Ser73 in the process of skin carcinogenesis and HI-TOPK-032 could be used as a potential chemopreventive drug against cSCC development.
• Soyer, H. P., Smithers, B. M., Whitty, J. A., Whiteman, D. C., Halpern, A., Hofman-Wellenhof, R., Curiel-Lewendrowski, C., Koh, U., Gillespie, N., Loescher, L. J., Vagenas, D., Horsham, C., & Janda, M. (2020). Accuracy of mobile digital teledermoscopy for skin self-examinations in adults at high risk of skin cancer: an open-label, randomized controlled trial. 2:. Lancet Digital Health, 2, e129-137. doi:https://doi.org/10.1016/S2589-7500(20)30001-7
• Varedi, A., Gardner, L. J., Kim, C. C., Chu, E. Y., Ming, M. E., Leachman, S. A., Curiel-Lewandrowski, C., Swetter, S. M., & Grossman, D. (2020). Use of new molecular tests for melanoma by pigmented-lesion experts. Journal of the American Academy of Dermatology, 82(1), 245-247.
• Wondrak, G. T., Dickinson, S. E., Curiel, C., Wondrak, G. T., Seligmann, B., Kirschnerova, V., Khawam, M., Dickinson, S. E., & Curiel, C. (2020). 640 CrispR/Cas9 deletion of TLR4 impacts the UV-induced stress response in human keratinocytes. Journal of Investigative Dermatology, 140(7), S86. doi:10.1016/j.jid.2020.03.651
• Zalaudek, I., Conforti, C., Corneli, P., Pizzichetta, M. A., Fadel, M., Mitija, G., Curiel-lewandrowski, C., Toncic, R. J., Pizzichetta, P., & Meo, N. D. (2020). Sun-protection and sun-exposure habits among sailors: results of the 2018 world's largest sailing race Barcolana' skin cancer prevention campaign.. Journal of the European Academy of Dermatology and Venereology : JEADV, 34(2), 412-418. doi:10.1111/jdv.15908
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  Epidemiologic data suggest an increased risk of melanoma (MM) and non-melanoma skin cancer (NMSC) in persons with intense recreational sun-exposure such as marathon runners or surfers. Up to data little is known about the sun-exposure habits, sun-protection behaviours and risk factors for MM and NMSC among sailors..The objective of this prospective, cross-sectional study was to investigate the sun-exposure and sun-protective habits and risk factors for skin cancer among sailors attending the 50° edition of Barcolana, the largest sailing race in of the world, which took place in October 2018 in Trieste, Italy as an integrative component of a public sun-prevention campaign..The study consisted of 2 parts: (i) a self-administered questionnaire focusing on sun-exposure and protective habits and (ii) a free skin examination carried out by volunteer dermatologists. Participation was optional and anonymous, and open to visitors and sailors attending the event..Overall, 431 (52.4%) sailors and 391 (47.6%) visitors responded to the questionnaire, while a total of 437 individuals including 189 (43.3%) sailors and 248 (56.6%) visitors participated in the skin examination group. The majority of sailors reported a past history of severe sunburns (20.2%), applied sunscreen never (14.4%) to sometimes (45.7%) or only once daily (59%) on the face (55%) and shoulders (26%). Moreover, 14% of sailors had a personal history of non-melanoma skin cancer (NMSC). During the dermatological examination, suspicious lesions for skin cancer (including MM and NMSC) were identified in 37% of the sailors..Our findings support the need to develop and promote primary and secondary prevention strategies to improve the sun-exposure and sun-protective habits among sailors.
• , W. G., Swetter, S. M., Tsao, H., Bichakjian, C. K., Curiel-Lewandrowski, C., Elder, D. E., Gershenwald, J. E., Guild, V., Grant-Kels, J. M., Halpern, A. C., Johnson, T. M., Sober, A. J., Thompson, J. A., Wisco, O. J., Wyatt, S., Hu, S., & Lamina, T. (2019). Guidelines of care for the management of primary cutaneous melanoma. Journal of the American Academy of Dermatology, 80(1), 208-250.
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  The incidence of primary cutaneous melanoma continues to increase each year. Melanoma accounts for the majority of skin cancer-related deaths, but treatment is usually curative following early detection of disease. In this American Academy of Dermatology clinical practice guideline, updated treatment recommendations are provided for patients with primary cutaneous melanoma (American Joint Committee on Cancer stages 0-IIC and pathologic stage III by virtue of a positive sentinel lymph node biopsy). Biopsy techniques for a lesion that is clinically suggestive of melanoma are reviewed, as are recommendations for the histopathologic interpretation of cutaneous melanoma. The use of laboratory, molecular, and imaging tests is examined in the initial work-up of patients with newly diagnosed melanoma and for follow-up of asymptomatic patients. With regard to treatment of primary cutaneous melanoma, recommendations for surgical margins and the concepts of staged excision (including Mohs micrographic surgery) and nonsurgical treatments for melanoma in situ, lentigo maligna type (including topical imiquimod and radiation therapy), are updated. The role of sentinel lymph node biopsy as a staging technique for cutaneous melanoma is described, with recommendations for its use in clinical practice. Finally, current data regarding pregnancy and melanoma, genetic testing for familial melanoma, and management of dermatologic toxicities related to novel targeted agents and immunotherapies for patients with advanced disease are summarized.
• Curiel-lewandrowski, C., Dickinson, S. E., Yozwiak, M., Saboda, K., Petricoin, E. F., Krutzsch, M., Dickinson, S. E., Curiel-lewandrowski, C., & Calvert, V. S. (2019). 771 Increased PD-L1 expression in human skin acutely and chronically exposed to UV irradiation. Journal of Investigative Dermatology, 139(5), S133. doi:10.1016/j.jid.2019.03.847
• Curiel-lewandrowski, C., Dickinson, S. E., Yozwiak, M., Saboda, K., Roe, D. J., Krutzsch, M., Dickinson, S. E., & Curiel-lewandrowski, C. (2019). 164 Increased PD-L1 and CD47 expression in high-risk cutaneous squamous cell carcinomas. Journal of Investigative Dermatology, 139(5), S29. doi:10.1016/j.jid.2019.03.240
• Gong, C., Kulkarni, N., Zhu, W., Nguyen, C. D., Curiel-Lewandrowski, C., & Kang, D. (2019). Low-cost, high-speed near infrared reflectance confocal microscope. Biomedical optics express, 10(7), 3497-3505.
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  We have developed a low-cost, near-infrared (NIR) reflectance confocal microscope (RCM) to overcome challenges in the imaging depth and speed found in our previously-reported smartphone confocal microscope. In the new NIR RCM device, we have used 840 nm superluminescent LED (sLED) to increase the tissue imaging depth and speed. A new confocal detection optics has been developed to maintain high lateral resolution even when a relatively large slit width was used. The material cost of the NIR RCM device was still low, ~$5,200. The lateral resolution was 1.1 µm and 1.3 µm along the vertical and horizontal directions, respectively. Axial resolution was measured as 11.2 µm. confocal images of human forearm skin obtained at the imaging speed of 203 frames/sec clearly visualized characteristic epidermal and dermal cellular features of the human skin.
• Grossman, D., Kim, C. C., Hartman, R. I., Berry, E., Nelson, K. C., Okwundu, N., Curiel-Lewandrowski, C., Leachman, S. A., & Swetter, S. M. (2019). Prognostic gene expression profiling in melanoma: necessary steps to incorporate into clinical practice. Melanoma management, 6(4), MMT32.
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  Prognostic gene expression profiling (GEP) tests for cutaneous melanoma (CM) are not recommended in current guidelines outside of a clinical trial. However, their use is becoming more prevalent and some practitioners are using GEP tests to guide patient management. Thus, there is an urgent need to bridge this gap between test usage and clinical guideline recommendations by obtaining high-quality evidence to guide us toward best practice use of GEP testing in CM patients. We focus here on the opportunities and uncertainties associated with prognostic GEP testing in CM, review how GEP testing was incorporated into clinical care guidelines for uveal melanoma and breast cancer and discuss the role of clinical trials to determine best use in patients with CM.
• Jeter, J. M., Bowles, T. L., Curiel-Lewandrowski, C., Swetter, S. M., Filipp, F. V., Abdel-Malek, Z. A., Geskin, L. J., Brewer, J. D., Arbiser, J. L., Gershenwald, J. E., Chu, E. Y., Kirkwood, J. M., Box, N. F., Funchain, P., Fisher, D. E., Kendra, K. L., Marghoob, A. A., Chen, S. C., Ming, M. E., , Albertini, M. R., et al. (2019). Chemoprevention agents for melanoma: A path forward into phase 3 clinical trials. Cancer, 125(1), 18-44.
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  Recent progress in the treatment of advanced melanoma has led to unprecedented improvements in overall survival and, as these new melanoma treatments have been developed and deployed in the clinic, much has been learned about the natural history of the disease. Now is the time to apply that knowledge toward the design and clinical evaluation of new chemoprevention agents. Melanoma chemoprevention has the potential to reduce dramatically both the morbidity and the high costs associated with treating patients who have metastatic disease. In this work, scientific and clinical melanoma experts from the national Melanoma Prevention Working Group, composed of National Cancer Trials Network investigators, discuss research aimed at discovering and developing (or repurposing) drugs and natural products for the prevention of melanoma and propose an updated pipeline for translating the most promising agents into the clinic. The mechanism of action, preclinical data, epidemiological evidence, and results from available clinical trials are discussed for each class of compounds. Selected keratinocyte carcinoma chemoprevention studies also are considered, and a rationale for their inclusion is presented. These data are summarized in a table that lists the type and level of evidence available for each class of agents. Also included in the discussion is an assessment of additional research necessary and the likelihood that a given compound may be a suitable candidate for a phase 3 clinical trial within the next 5 years.
• Jeter, J. M., Bowles, T. L., Curiel-lewandrowski, C., Swetter, S. M., Filipp, F. V., Abdel-malek, Z. A., Geskin, L. J., Brewer, J. D., Arbiser, J. L., Gershenwald, J. E., Chu, E. Y., Kirkwood, J. M., Box, N. F., Funchain, P., Fisher, D. E., Kendra, K., Marghoob, A. A., Chen, S. C., Ming, M. E., , Albertini, M. R., et al. (2019). Erratum: Jeter JM, Bowles TL, Curiel-Lewandrowski C, et al. Chemoprevention agents for melanoma: A path forward into phase 3 clinical trials. Cancer. 2019:125:18-44.. Cancer, 125(15), 2706. doi:10.1002/cncr.32075
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  Author(s): Jeter, Joanne M; Bowles, Tawnya L; Curiel-Lewandrowski, Clara; Swetter, Susan M; Filipp, Fabian V; Abdel-Malek, Zalfa A; Geskin, Larisa J; Brewer, Jerry D; Arbiser, Jack L; Gershenwald, Jeffrey E; Chu, Emily Y; Kirkwood, John M; Box, Neil F; Funchain, Pauline; Fisher, David E; Kendra, Kari L; Marghoob, Ashfaq A; Chen, Suephy C; Ming, Michael E; Albertini, Mark R; Vetto, John T; Margolin, Kim A; Pagoto, Sherry L; Hay, Jennifer L; Grossman, Douglas; Ellis, Darrel L; Kashani-Sabet, Mohammed; Mangold, Aaron R; Markovic, Svetomir N; Jr, Meyskens Frank L; Nelson, Kelly C; Powers, Jennifer G; Robinson, June K; Sahni, Debjani; Sekulic, Aleksandar; Sondak, Vernon K; Wei, Maria L; Zager, Jonathan S; Dellavalle, Robert P; Thompson, John A; Weinstock, Martin A; Leachman, Sancy A; Cassidy, Pamela B
• Maarouf, M., Costello, C. M., Gonzalez, S., Angulo, I., Curiel-Lewandrowski, C. N., & Shi, V. Y. (2019). In Vivo Reflectance Confocal Microscopy: Emerging Role in Noninvasive Diagnosis and Monitoring of Eczematous Dermatoses. Actas dermo-sifiliograficas, 110(8), 626-636.
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  Dermatologic diagnosis and monitoring have been dependent largely on visual grading. A skin biopsy is performed in case of diagnostic uncertainty, but can be traumatic, and results are delayed due to time for specimen transport and processing. Biopsies also destroy specimens, prohibiting lesion evolution monitoring. In vivo reflectance confocal microscopy (RCM) offers a diagnostic alternative to skin biopsy. RCM captures real-time, high-resolution images, and has been piloted for the evaluation of various dermatologic conditions. Identification of unique RCM features may distinguish dermatoses with similar clinical morphologies. Allergic contact dermatitis (ACD) and irritant contact dermatitis (ICD) are diagnosed by patch testing that currently uses a subjective scoring system. RCM has increasingly been studied for early detection and severity grading of CD. Common RCM features shared by ACD and ICD are stratum corneum disruption, vesicle formation, exocytosis, spongiosis, and parakeratosis. Features unique to ACD are vasodilation, increased epidermal thickness, intercellular edema, and acanthosis. Features unique to ICD are detached corneocytes and targetoid keratinocytes. This review summarizes the use of RCM in evaluating contact eccematous conditions and aims to spark future research and interest in this promising tool.
• Nelson, K. C., Swetter, S. M., Saboda, K., Chen, S. C., & Curiel-Lewandrowski, C. (2019). Evaluation of the Number-Needed-to-Biopsy Metric for the Diagnosis of Cutaneous Melanoma: A Systematic Review and Meta-analysis. JAMA dermatology.
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  To date, no concerted effort has been made to date to evaluate the literature on number-needed-to-biopsy (NNB) metrics, particularly to account for the differences in clinician type and melanoma prevalence in certain geographic locations.
• Waldman, R. A., Grant-Kels, J. M., Curiel, C. N., Curtis, J., Rodríguez, S. G., Hu, S., Kerr, P., Marghoob, A., Markowitz, O., Pellacani, G., Rabinovitz, H., Rao, B., Scope, A., Stein, J. A., & Swetter, S. M. (2019). Consensus Recommendations for the Use of Non-Invasive Melanoma Detection Techniques Based on Results of an International DELPHI Process. Journal of the American Academy of Dermatology.
• Zalaudek, I., Conforti, C., Corneli, P., Jurakic Toncic, R., di Meo, N., Pizzichetta, M. A., Fadel, M., Mitija, G., & Curiel-Lewandrowski, C. (2019). Sun-protection and sun-exposure habits among sailors: results of the 2018 world's largest sailing race Barcolana' skin cancer prevention campaign. Journal of the European Academy of Dermatology and Venereology : JEADV.
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  Epidemiologic data suggest an increased risk of melanoma (MM) and non-melanoma skin cancer (NMSC) in persons with intense recreational sun-exposure such as marathon runners or surfers. Up to data little is known about the sun-exposure habits, sun-protection behaviours and risk factors for MM and NMSC among sailors.
• Abraham, I., & Curiel-Lewandrowski, C. (2018). Staging Systems to Predict Metastatic Cutaneous Squamous Cell Carcinoma: Unsatisfactory for Clinical Use, but Some Less So?. JAMA dermatology, 154(12), 1391-1392.
• Almutairi, A. R., Alkhatib, N. S., Oh, M., Curiel-Lewandrowski, C., Babiker, H. M., Cranmer, L. D., McBride, A., & Abraham, I. (2018). Economic Evaluation of Talimogene Laherparepvec Plus Ipilimumab Combination Therapy vs Ipilimumab Monotherapy in Patients With Advanced Unresectable Melanoma. JAMA dermatology.
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  A phase 2 trial comparing talimogene laherparepvec plus ipilimumab vs ipilimumab monotherapy in patients with advanced unresectable melanoma found no differential benefit in progression-free survival (PFS) but noted objective response rates (ORRs) of 38.8% (38 of 98 patients) vs 18.0% (18 of 100 patients), respectively.
• Blohm-Mangone, K., Burkett, N. B., Tahsin, S., Myrdal, P. B., Aodah, A., Ho, B., Janda, J., McComas, M., Saboda, K., Roe, D. J., Dong, Z., Bode, A. M., Petricoin, E. F., Calvert, V. S., Curiel-Lewandrowski, C., Alberts, D. S., Wondrak, G. T., & Dickinson, S. E. (2018). Pharmacological TLR4 Antagonism Using Topical Resatorvid Blocks Solar UV-Induced Skin Tumorigenesis in SKH-1 Mice. Cancer Prevention Research, 11(5), 265-278.
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  An urgent need exists for the development of more efficacious molecular strategies targeting nonmelanoma skin cancer (NMSC), the most common malignancy worldwide. Inflammatory signaling downstream of Toll-like receptor 4 (TLR4) has been implicated in several forms of tumorigenesis, yet its role in solar UV-induced skin carcinogenesis remains undefined. We have previously shown in keratinocyte cell culture and SKH-1 mouse epidermis that topical application of the specific TLR4 antagonist resatorvid (TAK-242) blocks acute UV-induced AP-1 and NF-κB signaling, associated with downregulation of inflammatory mediators and MAP kinase phosphorylation. We therefore explored TLR4 as a novel target for chemoprevention of UV-induced NMSC. We selected the clinical TLR4 antagonist resatorvid based upon target specificity, potency, and physicochemical properties. Here, we confirm using permeability assays that topical resatorvid can be effectively delivered to skin, and using studies that topical resatorvid can block UV-induced AP-1 activation in mouse epidermis. We also report that in a UV-induced skin tumorigenesis model, topical resatorvid displays potent photochemopreventive activity, significantly suppressing tumor area and multiplicity. Tumors harvested from resatorvid-treated mice display reduced activity of UV-associated signaling pathways and a corresponding increase in apoptosis compared with tumors from control animals. Further mechanistic insight on resatorvid-based photochemoprevention was obtained from unsupervised hierarchical clustering analysis of protein readouts via reverse-phase protein microarray revealing a significant attenuation of key UV-induced proteomic changes by resatorvid in chronically treated high-risk SKH-1 skin prior to tumorigenesis. Taken together, our data identify TLR4 as a novel molecular target for topical photochemoprevention of NMSC. .
• Caffery, L. J., Clunie, D., Curiel-Lewandrowski, C., Malvehy, J., Soyer, H. P., & Halpern, A. C. (2018). Transforming Dermatologic Imaging for the Digital Era: Metadata and Standards. Journal of digital imaging, 31(4), 568-577.
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  Imaging is increasingly being used in dermatology for documentation, diagnosis, and management of cutaneous disease. The lack of standards for dermatologic imaging is an impediment to clinical uptake. Standardization can occur in image acquisition, terminology, interoperability, and metadata. This paper presents the International Skin Imaging Collaboration position on standardization of metadata for dermatologic imaging. Metadata is essential to ensure that dermatologic images are properly managed and interpreted. There are two standards-based approaches to recording and storing metadata in dermatologic imaging. The first uses standard consumer image file formats, and the second is the file format and metadata model developed for the Digital Imaging and Communication in Medicine (DICOM) standard. DICOM would appear to provide an advantage over using consumer image file formats for metadata as it includes all the patient, study, and technical metadata necessary to use images clinically. Whereas, consumer image file formats only include technical metadata and need to be used in conjunction with another actor-for example, an electronic medical record-to supply the patient and study metadata. The use of DICOM may have some ancillary benefits in dermatologic imaging including leveraging DICOM network and workflow services, interoperability of images and metadata, leveraging existing enterprise imaging infrastructure, greater patient safety, and better compliance to legislative requirements for image retention.
• Glazer, A. M., Stratton, D., & Curiel-Lewandrowski, C. (2018). Potential Underuse of the Sentinel Lymph Node Biopsy for High-Risk Squamous Cell Carcinoma of the Skin. JAMA dermatology, 154(8), 972-973.
• Kim, C. C., Berry, E. G., Marchetti, M. A., Swetter, S. M., Lim, G., Grossman, D., Curiel-Lewandrowski, C., Chu, E. Y., Ming, M. E., Zhu, K., Brahmbhatt, M., Balakrishnan, V., Davis, M. J., Wolner, Z., Fleming, N., Ferris, L. K., Nguyen, J., Trofymenko, O., Liu, Y., , Chen, S. C., et al. (2018). Risk of Subsequent Cutaneous Melanoma in Moderately Dysplastic Nevi Excisionally Biopsied but With Positive Histologic Margins. JAMA dermatology, 154(12), 1401-1408.
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  Little evidence exists to guide the management of moderately dysplastic nevi excisionally biopsied without residual clinical pigmentation but with positive histologic margins (hereafter referred to as moderately dysplastic nevi with positive histologic margins).
• Maarouf, M., Curiel-Lewandrowski, C., Daley, S., Kuo, P., Elquza, E., & Shi, V. Y. (2018). Cutaneous erysipeloid metastasis of cholangiocarcinoma and evaluation by in vivo reflectance confocal microscopy. JAAD case reports, 4(9), 918-920.
• Nelson, K. C., Grossman, D., Kim, C. C., Chen, S. C., Curiel-Lewandrowski, C. N., Grichnik, J. M., Kirkwood, J. M., Leachman, S. A., Marghoob, A. A., Swetter, S. M., Venna, S. S., & Ming, M. E. (2018). Management Strategies of Academic Pigmented Lesion Clinic Directors in the United States. Journal of the American Academy of Dermatology.
• Roh, E., Lee, M. H., Zykova, T. A., Zhu, F., Nadas, J., Kim, H. G., Bae, K. B., Li, Y., Cho, Y. Y., Curiel-Lewandrowski, C., Einspahr, J., Dickinson, S. E., Bode, A. M., & Dong, Z. (2018). Targeting PRPK and TOPK for skin cancer prevention and therapy. Oncogene, 37(42), 5633-5647.
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  Solar ultraviolet (sUV) irradiation is a major environmental carcinogen that can cause inflammation and skin cancer. The costs and morbidity associated with skin cancer are increasing, and therefore identifying molecules that can help prevent skin carcinogenesis is important. In this study, we identified the p53-related protein kinase (PRPK) as a novel oncogenic protein that is phosphorylated by the T-LAK cell-originated protein kinase (TOPK). Knockdown of TOPK inhibited PRPK phosphorylation and conferred resistance to solar-simulated light (SSL)-induced skin carcinogenesis in mouse models. In the clinic, acute SSL irradiation significantly increased epidermal thickness as well as total protein and phosphorylation levels of TOPK and PRPK in human skin tissues. We identified two PRPK inhibitors, FDA-approved rocuronium bromide (Zemuron) or betamethasone 17-valerate (Betaderm) that could attenuate TOPK-dependent PRPK signaling. Importantly, topical application of either rocuronium bromide or betamethasone decreased SSL-induced epidermal hyperplasia, neovascularization, and cutaneous squamous cell carcinoma (cSCC) development in SKH1 (Crl: SKH1-Hr) hairless mice by inhibiting PRPK activation, and also reduced expression of the proliferation and oncogenesis markers, COX-2, cyclin D1, and MMP-9. This study is the first to demonstrate that targeting PRPK could be useful against sUV-induced cSCC development.
• Swetter, S. M., Curiel-lewandrowski, C., Nelson, K. C., & Chen, S. C. (2018). The estimated financial impact of diagnostic accuracy on melanoma diagnosis in 2018.. Journal of Clinical Oncology, 36(15_suppl), e18903-e18903. doi:10.1200/jco.2018.36.15_suppl.e18903
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  e18903Background: Early melanoma diagnosis improves survival; provider diagnostic accuracy for melanoma varies significantly with potential financial implications. Methods: A systematic literature ...
• Trofymenko, O., & Curiel-lewandrowski, C. (2018). Surgical treatment associated with improved survival in patients with cutaneous angiosarcoma.. Journal of the European Academy of Dermatology and Venereology : JEADV, 32(1), e29-e31. doi:10.1111/jdv.14479
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  Cutaneous angiosarcoma is a rare aggressive vasoformative neoplasm of the skin with a poor prognosis.1 The neoplasm preferentially involves areas of head and neck and usually diagnosed in advanced stage.1, 2 The neoplasm accounts for only 2% of soft-tissue sarcomas in the U.S. and most often affects elderly white males, patients treated with radiation, and individuals with certain chronic lymphatic disorders.3 Surgery with or without adjuvant or neoadjuvant radiation therapy (RT) is considered the mainstay of therapy.1, 3 Due to low incidence rates, the clinical outcomes data has been limited to case reports and single institution studies, with a lack of direct comparison between various treatment modalities: surgery, RT, and chemotherapy (CT).4, 5 In this study, we aimed to investigate the impact of undergoing different therapeutic approaches on long-term overall survival (OS) using cross-institutional data. This article is protected by copyright. All rights reserved.
• Covington, M. F., Curiel, C. N., Lattimore, L., Avery, R. J., & Kuo, P. H. (2017). FDG-PET/CT for Monitoring Response of Melanoma to the Novel Oncolytic Viral Therapy Talimogene Laherparepvec. Clinical nuclear medicine, 42(2), 114-115.
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  61-year-old woman with stage IIIa (T3a N1a M0) left lower leg melanoma with lesions suggestive of in-transit metastases 8 months following wide local excision and femoral nodal dissection. FDG-PET/CT demonstrated 5 FDG-avid in-transit nodal metastases in the distal left leg, confirmed on biopsy. Talimogene laherparepvec (T-VEC) oncolytic immunotherapy consisting of intralesional injections of modified herpes simplex virus-expressing granulocyte-macrophage colony-stimulating factor was completed over 6 months. Subsequent FDG-PET/CT demonstrated reduced or resolved FDG activity in the treated in-transit metastases and a new FDG-avid left thigh in-transit metastasis. FDG-PET/CT can monitor response to T-VEC and potentially other novel viral immunotherapies.
• Dickinson, S. E., Myrdal, P. B., Curiel-lewandrowski, C., Wondrak, G. T., Tahsin, S., Saboda, K., Roe, D. J., Petricoin, E. F., Myrdal, P. B., Karlage, K. L., Janda, J., Dong, Z., Dickinson, S. E., Curiel-lewandrowski, C., Calvert, V. S., Burkett, N. B., Bode, A. M., Blohm-mangone, K. A., & Alberts, D. S. (2017). Abstract 2244: Pharmacological TLR4 antagonism using topical resatorvid blocks solar UV-induced skin tumorigenesis in SKH-1 mice. Cancer Research, 77, 2244-2244. doi:10.1158/1538-7445.am2017-2244
• Dong, Z., Curiel-lewandrowski, C., Myrdal, P. B., Dickinson, S. E., Wondrak, G. T., Tahsin, S., Saboda, K., Petricoin, E. F., Myrdal, P. B., Janda, J., Dong, Z., Dickinson, S. E., Curiel-lewandrowski, C., Calvert, V. S., Burkett, N. B., Bode, A. M., Blohm-mangone, K. A., & Aodah, A. (2017). 764 A novel strategy for topical photochemoprevention: Pharmacological TLR4 antagonism blocks non-melanoma skin cancer. Journal of Investigative Dermatology, 137(5), S131. doi:10.1016/j.jid.2017.02.788
• Einspahr, J. G., Curiel-Lewandrowski, C., Calvert, V. S., Stratton, S. P., Alberts, D. S., Warneke, J., Hu, C., Saboda, K., Wagener, E. L., Dickinson, S., Dong, Z., Bode, A. M., & PetricoinIII, E. F. (2017). Protein activation mapping of human sun-protected epidermis after an acute dose of erythemic solar simulated light. NPJ precision oncology, 1.
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  Ultraviolet radiation is an important etiologic factor in skin cancer and a better understanding of how solar stimulated light (SSL) affects signal transduction pathways in human skin which is needed in further understanding activated networks that could be targeted for skin cancer prevention. We utilized Reverse Phase Protein Microarray Analysis (RPPA), a powerful technology that allows for broad-scale and quantitative measurement of the activation/phosphorylation state of hundreds of key signaling proteins and protein pathways in sun-protected skin after an acute dose of two minimal erythema dose (MED) of SSL. RPPA analysis was used to map the altered cell signaling networks resulting from acute doses of solar simulated radiation (SSL). To that end, we exposed sun-protected skin in volunteers to acute doses of two MED of SSL and collected biopsies pre-SSL and post-SSL irradiation. Frozen biopsies were subjected to laser capture microdissection (LCM) and then assessed by RPPA. The activation/phosphorylation or total levels of 128 key signaling proteins and drug targets were selected for statistical analysis. Coordinate network-based analysis was performed on specific signaling pathways that included the PI3k/Akt/mTOR and Ras/Raf/MEK/ERK pathways. Overall, we found early and sustained activation of the PI3K-AKT-mTOR and MAPK pathways. Cell death and apoptosis-related proteins were activated at 5 and 24 h. Ultimately, expression profile patterns of phosphorylated proteins in the epidermal growth factor receptor (EGFR), AKT, mTOR, and other relevant pathways may be used to determine pharmacodynamic activity of new and selective topical chemoprevention agents administered in a test area exposed to SSL to determine drug-induced attenuation or reversal of skin carcinogenesis pathways.
• Finnane, A., Curiel-Lewandrowski, C., Wimberley, G., Caffery, L., Katragadda, C., Halpern, A., Marghoob, A. A., Malvehy, J., Kittler, H., Hofmann-Wellenhof, R., Abraham, I., Soyer, H. P., & , I. S. (2017). Proposed Technical Guidelines for the Acquisition of Clinical Images of Skin-Related Conditions. JAMA dermatology, 153(5), 453-457.
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  Standardizing dermatological imaging is important to improve monitoring of skin lesions and skin conditions, ensure the availability of high-quality images for teledermatology, and contribute to the development of a robust archive of skin images to be used for research.
• Gao, G., Zhang, T., Wang, Q., Reddy, K., Chen, H., Yao, K., Wang, K., Roh, E., Zykova, T., Ma, W., Ryu, J., Curiel-Lewandrowski, C., Alberts, D., Dickinson, S. E., Bode, A. M., Xing, Y., & Dong, Z. (2017). ADA-07 Suppresses Solar Ultraviolet-Induced Skin Carcinogenesis by Directly Inhibiting TOPK. Molecular cancer therapeutics, 16(9), 1843-1854.
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  Cumulative exposure to solar ultraviolet (SUV) irradiation is regarded as the major etiologic factor in the development of skin cancer. The activation of the MAPK cascades occurs rapidly and is vital in the regulation of SUV-induced cellular responses. The T-LAK cell-originated protein kinase (TOPK), an upstream activator of MAPKs, is heavily involved in inflammation, DNA damage, and tumor development. However, the chemopreventive and therapeutic effects of specific TOPK inhibitors in SUV-induced skin cancer have not yet been elucidated. In the current study, ADA-07, a novel TOPK inhibitor, was synthesized and characterized. Pull-down assay results, ATP competition, and in vitro kinase assay data revealed that ADA-07 interacted with TOPK at the ATP-binding pocket and inhibited its kinase activity. Western blot analysis showed that ADA-07 suppressed SUV-induced phosphorylation of ERK1/2, p38, and JNKs and subsequently inhibited AP-1 activity. Importantly, topical treatment with ADA-07 dramatically attenuated tumor incidence, multiplicity, and volume in SKH-1 hairless mice exposed to chronic SUV. Our findings suggest that ADA-07 is a promising chemopreventive or potential therapeutic agent against SUV-induced skin carcinogenesis that acts by specifically targeting TOPK. Mol Cancer Ther; 16(9); 1843-54. ©2017 AACR.
• Garrett, G. L., Blanc, P. D., Boscardin, J., Lloyd, A. A., Ahmed, R. L., Anthony, T., Bibee, K., Breithaupt, A., Cannon, J., Chen, A., Cheng, J. Y., Chiesa-Fuxench, Z., Colegio, O. R., Curiel-Lewandrowski, C., Del Guzzo, C. A., Disse, M., Dowd, M., Eilers, R., Ortiz, A. E., , Morris, C., et al. (2017). Incidence of and Risk Factors for Skin Cancer in Organ Transplant Recipients in the United States. JAMA dermatology.
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  Skin cancer is the most common malignancy occurring after organ transplantation. Although previous research has reported an increased risk of skin cancer in solid organ transplant recipients (OTRs), no study has estimated the posttransplant population-based incidence in the United States.
• Johnson, M. M., Leachman, S. A., Aspinwall, L. G., Cranmer, L. D., Curiel-Lewandrowski, C., Sondak, V. K., Stemwedel, C. E., Swetter, S. M., Vetto, J., Bowles, T., Dellavalle, R. P., Geskin, L. J., Grossman, D., Grossmann, K. F., Hawkes, J. E., Jeter, J. M., Kim, C. C., Kirkwood, J. M., Mangold, A. R., , Meyskens, F., et al. (2017). Skin cancer screening: recommendations for data-driven screening guidelines and a review of the US Preventive Services Task Force controversy. Melanoma management, 4(1), 13-37.
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  Melanoma is usually apparent on the skin and readily detected by trained medical providers using a routine total body skin examination, yet this malignancy is responsible for the majority of skin cancer-related deaths. Currently, there is no national consensus on skin cancer screening in the USA, but dermatologists and primary care providers are routinely confronted with making the decision about when to recommend total body skin examinations and at what interval. The objectives of this paper are: to propose rational, risk-based, data-driven guidelines commensurate with the US Preventive Services Task Force screening guidelines for other disorders; to compare our proposed guidelines to recommendations made by other national and international organizations; and to review the US Preventive Services Task Force's 2016 Draft Recommendation Statement on skin cancer screening.
• Kurtzman, D. J., Oulton, J., Erickson, C., & Curiel-Lewandrowski, C. (2017). Everolimus-Induced Symmetrical Drug-Related Intertriginous and Flexural Exanthema (SDRIFE). Dermatitis : contact, atopic, occupational, drug, 27(2), 76-7.
• Teves, J. M., Bhargava, V., Kirwan, K. R., Corenblum, M. J., Justiniano, R., Wondrak, G. T., Anandhan, A., Flores, A. J., Schipper, D. A., Khalpey, Z., Sligh, J. E., Curiel-Lewandrowski, C., Sherman, S. J., & Madhavan, L. (2017). Parkinson's Disease Skin Fibroblasts Display Signature Alterations in Growth, Redox Homeostasis, Mitochondrial Function, and Autophagy. Frontiers in neuroscience, 11, 737.
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  The discovery of biomarkers for Parkinson's disease (PD) is challenging due to the heterogeneous nature of this disorder, and a poor correlation between the underlying pathology and the clinically expressed phenotype. An ideal biomarker would inform on PD-relevant pathological changes via an easily assayed biological characteristic, which reliably tracks clinical symptoms. Human dermal (skin) fibroblasts are accessible peripheral cells that constitute a patient-specific system, which potentially recapitulates the PD chronological and epigenetic aging history. Here, we compared primary skin fibroblasts obtained from individuals diagnosed with late-onset sporadic PD, and healthy age-matched controls. These fibroblasts were studied from fundamental viewpoints of growth and morphology, as well as redox, mitochondrial, and autophagic function. It was observed that fibroblasts from PD subjects had higher growth rates, and appeared distinctly different in terms of morphology and spatial organization in culture, compared to control cells. It was also found that the PD fibroblasts exhibited significantly compromised mitochondrial structure and function when assessed via morphological and oxidative phosphorylation assays. Additionally, a striking increase in baseline macroautophagy levels was seen in cells from PD subjects. Exposure of the skin fibroblasts to physiologically relevant stress, specifically ultraviolet irradiation (UVA), further exaggerated the autophagic dysfunction in the PD cells. Moreover, the PD fibroblasts accumulated higher levels of reactive oxygen species (ROS) coupled with lower cell viability upon UVA treatment. In essence, these studies highlight primary skin fibroblasts as a patient-relevant model that captures fundamental PD molecular mechanisms, and supports their potential utility to develop diagnostic and prognostic biomarkers for the disease.
• Trofymenko, O., & Curiel-Lewandrowski, C. (2017). Surgical treatment associated with improved survival in patients with cutaneous angiosarcoma. Journal of the European Academy of Dermatology and Venereology : JEADV.
• Arzberger, E., Curiel-Lewandrowski, C., Blum, A., Chubisov, D., Oakley, A., Rademaker, M., Soyer, H., & Hofmann-Wellenhof, R. (2016). Teledermoscopy in High-risk Melanoma Patients: A Comparative Study of Face-to-face and Teledermatology Visits. Acta dermato-venereologica.
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  Teledermoscopy is considered a reliable tool for the evaluation of pigmented skin lesions. We compared the management decision in face-to-face visits vs. teledermatology in a high-risk melanoma cohort using total-body photography, macroscopic and dermoscopic images of single lesions. Patients were assessed both face-to face and by 4 remote teledermatologists. Lesions identified as suspicious for skin cancer by face-to-face evaluation underwent surgical excision. The teledermatologists recommended "self-monitoring", "short-term monitoring", or "excision". A 4-year monitoring was completed in a cohort of participating subjects. The general agreement, calculated by prevalence and bias-adjusted κ (PABAK), showed almost perfect agreement (PABAK 0.9-0.982). A total of 23 lesions were excised; all teledermatologists identified the 9 melanomas. The greatest discrepancy was detected in "short-term monitoring". During 4-year monitoring one melanoma was excised that had been considered benign. In conclusion, melanoma identification by experts in pigmented lesions appears to be equivalent between face-to-face and teledermatological consultation.
• Curiel-Lewandrowski, C. N., Krase, I., & Cavanaugh, K. (2016). Rupoid Syphilis. J am Acad Dermatol.
• Curiel-Lewandrowski, C., & Swetter, S. M. (2016). Lack of harms from community-based melanoma screening by primary care providers. Cancer, 122(20), 3102-3105.
• Dickinson, S. E., Janda, J., Criswell, J., Blohm-Mangone, K., Olson, E. R., Liu, Z., Barber, C., Rusche, J. J., Petricoin, E., Calvert, V., Einspahr, J. G., Dickinson, J. E., Stratton, S. P., Curiel-Lewandrowski, C., Saboda, K., Hu, C., Bode, A. M., Dong, Z., Alberts, D. S., & Bowden, G. T. (2016). Inhibition of Akt Enhances the Chemopreventive Effects of Topical Rapamycin in Mouse Skin. Cancer prevention research (Philadelphia, Pa.).
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  The PI3Kinase/Akt/mTOR pathway has important roles in cancer development for multiple tumor types, including UV-induced non-melanoma skin cancer. Immunosuppressed populations are at increased risk of aggressive cutaneous squamous cell carcinoma (SCC). Individuals who are treated with rapamycin, (sirolimus, a classical mTOR inhibitor) have significantly decreased rates of developing new cutaneous SCCs compared to those that receive traditional immunosuppression. However, systemic rapamycin use can lead to significant adverse events. Here we explored the use of topical rapamycin as a chemopreventive agent in the context of solar simulated light (SSL)-induced skin carcinogenesis. In SKH-1 mice, topical rapamycin treatment decreased tumor yields when applied after completion of 15 weeks of SSL exposure compared to controls. However, applying rapamycin during SSL exposure for 15 weeks, and continuing for 10 weeks after UV treatment, increased tumor yields. We also examined whether a combinatorial approach might result in more significant tumor suppression by rapamycin. We validated that rapamycin causes increased Akt (S473) phosphorylation in the epidermis after SSL, and show for the first time that this dysregulation can be inhibited in vivo by a selective PDK1/Akt inhibitor, PHT-427. Combining rapamycin with PHT-427 on tumor prone skin additively caused a significant reduction of tumor multiplicity compared to vehicle controls. Our findings indicate that patients taking rapamycin should avoid sun exposure, and that combining topical mTOR inhibitors and Akt inhibitors may be a viable chemoprevention option for individuals at high risk for cutaneous SCC.
• Einspahr, J. G., Bowden, G. T., Alberts, D. S., McKenzie, N., Saboda, K., Warneke, J., Salasche, S., Ranger-Moore, J., Curiel-Lewandrowski, C., Nagle, R. B., Nickoloff, B. J., Brooks, C., Dong, Z., & Stratton, S. P. (2016). Cross-validation of murine UV signal transduction pathways in human skin. Photochemistry and photobiology, 84(2), 463-76.
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  Acute UVB irradiation of mouse skin results in activation of phospatidyinositol-3 (PI-3) kinase and mitogen-activated protein kinase (MAPK) pathways leading to altered protein phosphorylation and downstream transcription of genes. We determined whether activation of these pathways also occurs in human skin exposed to 4x minimal erythemic dose of UVB in 23 volunteers. Biopsies were taken prior to, at 30 min, 1 and 24 h post-UVB. In agreement with mouse studies, the earliest UV-induced changes in epidermis were seen in phospho-CREB (two- and five-fold at 30 min and 1 h) and in phospho-MAPKAPK-2 (three-fold at both 30 min and 1 h). At 1 h, phospho-c-JUN and phospho-p38 were increased five- and two-fold, respectively. Moreover, phospho-c-JUN and phospho-p38 were further increased at 24 h (12- and six-fold, respectively). Phospho-GSK-3beta was similarly increased at all time points. Increases in phospho-p53 (12-fold), COX-2 (four-fold), c-FOS (14-fold) and apoptosis were not seen until 24 h. Our data suggest that UVB acts through MAPK p38 and PI-3 kinase with phosphorylation of MAPKAPK-2, CREB, c-JUN, p38, GSK-3beta and p53 leading to marked increases in c-FOS, COX-2 and apoptosis. Validation of murine models in human skin will aid in development of effective skin cancer chemoprevention and prevention strategies.
• Einspahr, J. G., Dickinson, S. E., Dong, Z., Curiel-lewandrowski, C., Warneke, J. A., Warneke, J. A., Stratton, S. P., Petricoin, E. F., Einspahr, J. G., Dong, Z., Dickinson, S. E., Curiel-lewandrowski, C., Bode, A. M., & Alberts, D. S. (2016). 575 Immunohistochemical evaluation of proteins within UV signal transduction pathways in the progression of normal human skin to matched sun-damaged skin and actinic keratosis. Journal of Investigative Dermatology, 136(5), S102. doi:10.1016/j.jid.2016.02.614
• Einspahr, J. G., Dong, Z., Curiel-lewandrowski, C., Dickinson, S. E., Wondrak, G. T., Janda, J., Einspahr, J. G., Dong, Z., Dickinson, S. E., Curiel-lewandrowski, C., Burkett, N. B., Bode, A. M., Blohm-mangone, K. A., & Alberts, D. S. (2016). 085 TLR4 as a novel molecular target for non-melanoma skin cancer prevention. Journal of Investigative Dermatology, 136(5), S15. doi:10.1016/j.jid.2016.02.111
• Janda, J., Burkett, N. B., Blohm-Mangone, K., Huang, V., Curiel-Lewandrowski, C., Alberts, D. S., Petricoin, E. F., Calvert, V. S., Einspahr, J., Dong, Z., Bode, A. M., Wondrak, G. T., & Dickinson, S. E. (2016). Resatorvid-based Pharmacological Antagonism of Cutaneous TLR4 Blocks UV-induced NF-κB and AP-1 Signaling in Keratinocytes and Mouse Skin. Photochemistry and photobiology, 92(6), 816-825.
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  Cutaneous exposure to solar ultraviolet (UV) radiation is a major causative factor in skin carcinogenesis, and improved molecular strategies for efficacious chemoprevention of nonmelanoma skin cancer (NMSC) are urgently needed. Toll-like receptor 4 (TLR4) signaling has been shown to drive skin inflammation, photoimmunosuppression, and chemical carcinogenesis. Here we have examined the feasibility of genetic and pharmacological antagonism targeting cutaneous TLR4 for the suppression of UV-induced NF-κB and AP-1 signaling in keratinocytes and mouse skin. Using immunohistochemical and proteomic microarray analysis of human skin, we demonstrate for the first time that a significant increase in expression of TLR4 occurs in keratinocytes during the progression from normal skin to actinic keratosis, also detectible during further progression to squamous cell carcinoma. Next, we demonstrate that siRNA-based genetic TLR4 inhibition blocks UV-induced stress signaling in cultured keratinocytes. Importantly, we observed that resatorvid (TAK-242), a molecularly targeted clinical TLR4 antagonist, blocks UV-induced NF-κB and MAP kinase/AP-1 activity and cytokine expression (Il-6, Il-8, and Il-10) in cultured keratinocytes and in topically treated murine skin. Taken together, our data reveal that pharmacological TLR4 antagonism can suppress UV-induced cutaneous signaling, and future experiments will explore the potential of TLR4-directed strategies for prevention of NMSC.
• Katragadda, C., Finnane, A., Soyer, H. P., Marghoob, A. A., Halpern, A., Malvehy, J., Kittler, H., Hofmann-Wellenhof, R., Da Silva, D., Abraham, I., Curiel-Lewandrowski, C., & , I. S. (2016). Technique Standards for Skin Lesion Imaging: A Delphi Consensus Statement. JAMA dermatology.
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  Variability in the metrics for image acquisition at the total body, regional, close-up, and dermoscopic levels impacts the quality and generalizability of skin images. Consensus guidelines are indicated to achieve universal imaging standards in dermatology.
• Kittler, H., Marghoob, A. A., Argenziano, G., Carrera, C., Curiel-Lewandrowski, C., Hofmann-Wellenhof, R., Malvehy, J., Menzies, S., Puig, S., Rabinovitz, H., Stolz, W., Saida, T., Soyer, H. P., Siegel, E., Stoecker, W. V., Scope, A., Tanaka, M., Thomas, L., Tschandl, P., , Zalaudek, I., et al. (2016). Standardization of terminology in dermoscopy/dermatoscopy: Results of the third consensus conference of the International Society of Dermoscopy. Journal of the American Academy of Dermatology.
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  Evolving dermoscopic terminology motivated us to initiate a new consensus.
• Krase, I. Z., Cavanaugh, K., & Curiel-Lewandrowski, C. (2016). A case of rupioid syphilis. JAAD case reports, 2(2), 141-3.
• Krase, I. Z., Cavanaugh, K., & Curiel-lewandrowski, C. (2016). Treatment of Refractory Pityriasis Rubra Pilaris With Novel Phosphodiesterase 4 (PDE4) Inhibitor Apremilast.. JAMA dermatology, 152(3), 348-50. doi:10.1001/jamadermatol.2015.3405
• Kurtzman, D. J., Thiede, R., Erickson, C., & Curiel-Lewandrowski, C. (2016). An abrupt onset pustular eruption. Journal of the American Academy of Dermatology, 75(2), e45-6.
• Kurtzman, D., Oulton, J., Erickson, C., & Curiel-Lewandrowski, C. N. (2016). Everolimus-induced SDRIFE. Am J Med.
• Leachman, S. A., Cassidy, P. B., Chen, S. C., Curiel, C., Geller, A., Gareau, D., Pellacani, G., Grichnik, J. M., Malvehy, J., North, J., Jacques, S. L., Petrie, T., Puig, S., Swetter, S. M., Tofte, S., & Weinstock, M. A. (2016). Methods of Melanoma Detection. Cancer treatment and research, 167, 51-105.
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  Detection and removal of melanoma, before it has metastasized, dramatically improves prognosis and survival. The purpose of this chapter is to (1) summarize current methods of melanoma detection and (2) review state-of-the-art detection methods and technologies that have the potential to reduce melanoma mortality. Current strategies for the detection of melanoma range from population-based educational campaigns and screening to the use of algorithm-driven imaging technologies and performance of assays that identify markers of transformation. This chapter will begin by describing state-of-the-art methods for educating and increasing awareness of at-risk individuals and for performing comprehensive screening examinations. Standard and advanced photographic methods designed to improve reliability and reproducibility of the clinical examination will also be reviewed. Devices that magnify and/or enhance malignant features of individual melanocytic lesions (and algorithms that are available to interpret the results obtained from these devices) will be compared and contrasted. In vivo confocal microscopy and other cellular-level in vivo technologies will be compared to traditional tissue biopsy, and the role of a noninvasive "optical biopsy" in the clinical setting will be discussed. Finally, cellular and molecular methods that have been applied to the diagnosis of melanoma, such as comparative genomic hybridization (CGH), fluorescent in situ hybridization (FISH), and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), will be discussed.
• Merlino, G., Herlyn, M., Fisher, D. E., Bastian, B. C., Flaherty, K. T., Davies, M. A., Wargo, J. A., Curiel-Lewandrowski, C., Weber, M. J., Leachman, S. A., Soengas, M. S., McMahon, M., Harbour, J. W., Swetter, S. M., Aplin, A. E., Atkins, M. B., Bosenberg, M. W., Dummer, R., Gershenwald, J. E., , Halpern, A. C., et al. (2016). The state of melanoma: challenges and opportunities. Pigment cell & melanoma research, 29(4), 404-16.
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  The Melanoma Research Foundation (MRF) has charted a comprehensive assessment of the current state of melanoma research and care. Intensive discussions among members of the MRF Scientific Advisory Council and Breakthrough Consortium, a group that included clinicians and scientists, focused on four thematic areas - diagnosis/early detection, prevention, tumor cell dormancy (including metastasis), and therapy (response and resistance). These discussions extended over the course of 2015 and culminated at the Society of Melanoma Research 2015 International Congress in November. Each of the four groups has outlined their thoughts as per the current status, challenges, and opportunities in the four respective areas. The current state and immediate and long-term needs of the melanoma field, from basic research to clinical management, are presented in the following report.
• Richtig, E., Asslaber, M., Partl, R., Avian, A., Berghold, A., Preusser, M., Becker, J. C., Curiel-lewandrowski, C., & Kapp, K. S. (2016). Lack of P-glycoprotein expression in melanoma brain metastases of different melanoma types.. Clinical neuropathology, 35(2), 89-92. doi:10.5414/np300903
• Bermudez, Y., Stratton, S. P., Curiel-Lewandrowski, C., Warneke, J., Hu, C., Bowden, G. T., Dickinson, S. E., Dong, Z., Bode, A. M., Saboda, K., Brooks, C. A., Petricoin, E. F., Hurst, C. A., Alberts, D. S., & Einspahr, J. G. (2015). Activation of the PI3K/Akt/mTOR and MAPK Signaling Pathways in Response to Acute Solar-Simulated Light Exposure of Human Skin. Cancer prevention research (Philadelphia, Pa.), 8(8), 720-8.
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  The incidence of skin cancer is higher than all other cancers and continues to increase, with an average annual cost over $8 billion in the United States. As a result, identifying molecular pathway alterations that occur with UV exposure to strategize more effective preventive and therapeutic approaches is essential. To that end, we evaluated phosphorylation of proteins within the PI3K/Akt and MAPK pathways by immunohistochemistry in sun-protected skin after acute doses of physiologically relevant solar-simulated ultraviolet light (SSL) in 24 volunteers. Biopsies were performed at baseline, 5 minutes, 1, 5, and 24 hours after SSL irradiation. Within the PI3K/Akt pathway, we found activation of Akt (serine 473) to be significantly increased at 5 hours while mTOR (serine 2448) was strongly activated early and was sustained over 24 hours after SSL. Downstream, we observed a marked and sustained increase in phospho-S6 (serine 235/S236), whereas phospho-4E-BP1 (threonines 37/46) was increased only at 24 hours. Within the MAPK pathway, SSL-induced expression of phospho-p38 (threonine 180/tyrosine 182) peaked at 1 to 5 hours. ERK 1/2 was observed to be immediate and sustained after SSL irradiation. Phosphorylation of histone H3 (serine 10), a core structural protein of the nucleosome, peaked at 5 hours after SSL irradiation. The expression of both p53 and COX-2 was increased at 5 hours and was maximal at 24 hours after SSL irradiation. Apoptosis was significantly increased at 24 hours as expected and indicative of a sunburn-type response to SSL. Understanding the timing of key protein expression changes in response to SSL will aid in development of mechanistic-based approaches for the prevention and control of skin cancers.
• Curiel-Lewandrowski, C., Tang, J. Y., Einspahr, J. G., Bermudez, Y., Hsu, C. H., Rezaee, M., Lee, A. H., Tangrea, J., Parnes, H. L., Alberts, D. S., & Chow, H. S. (2015). Pilot study on the bioactivity of vitamin d in the skin after oral supplementation. Cancer prevention research (Philadelphia, Pa.), 8(6), 563-9.
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  Laboratory studies suggest that vitamin D (VD) supplementation inhibits skin carcinogenesis. However, epidemiologic studies report mixed findings in the association between circulating VD levels and skin cancer risk. We conducted a clinical study to determine whether oral cholecalciferol supplementation would exert direct bioactivity in human skin through modulation of the VD receptor (VDR). We enrolled 25 individuals with serum 25-hydroxyvitamin-D levels
• Jeter, J. M., Curiel-Lewandrowski, C., Stratton, S. P., Myrdal, P. B., Warneke, J. A., Einspahr, J. G., Bartels, H., Yozwiak, M., Bermudez, Y., Hu, C., Bartels, P., & Alberts, D. S. (2015). Phase IIB Randomized Study of Topical Difluoromethylornithine and Topical Diclofenac on Sun-Damaged Skin of the Forearm. Cancer prevention research (Philadelphia, Pa.).
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  Prevention of nonmelanoma skin cancers remains a health priority due to high costs associated with this disease. Diclofenac and difluoromethylornithine (DFMO) have demonstrated chemopreventative efficacy for cutaneous squamous cell carcinomas. We designed a randomized study of the combination of DFMO and diclofenac in the treatment of sun-damaged skin. Individuals with visible cutaneous sun damage were eligible. Subjects were randomized to one of three groups: topical DFMO applied twice daily, topical diclofenac applied daily, or DFMO plus diclofenac. The treatment was limited to an area on the left forearm, and the duration of use was 90 days. We hypothesized that combination therapy would have increased efficacy compared to single-agent therapy. The primary outcome was change in karyometric average nuclear abnormality (ANA) in the treated skin. Individuals assessing the biomarkers were blinded regarding the treatment for each subject. A total of 156 subjects were randomized; 144 had baseline and end-of-study biopsies, and 136 subjects completed the study. The ANA unexpectedly increased for all groups, with higher values correlating with clinical cutaneous inflammation. Nearly all of the adverse events were local cutaneous effects. One subject had cutaneous toxicity that required treatment discontinuation. Significantly more adverse events were seen in the groups taking diclofenac. Overall, the study indicated that the addition of topical DFMO to topical diclofenac did not enhance its activity. Both agents caused inflammation on a cellular and clinical level, which may have confounded the measurement of chemopreventative effects. More significant effects may be observed in subjects with greater baseline cutaneous damage.
• Kim, C. C., Swetter, S. M., Curiel-Lewandrowski, C., Grichnik, J. M., Grossman, D., Halpern, A. C., Kirkwood, J. M., Leachman, S. A., Marghoob, A. A., Ming, M. E., Nelson, K. C., Veledar, E., Venna, S. S., & Chen, S. C. (2015). Addressing the knowledge gap in clinical recommendations for management and complete excision of clinically atypical nevi/dysplastic nevi: Pigmented Lesion Subcommittee consensus statement. JAMA dermatology, 151(2), 212-8.
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  The management of clinically atypical nevi/dysplastic nevi (CAN/DN) is controversial, with few data to guide the process. Management recommendations for DN with positive histologic margins were developed by the Delphi method to achieve consensus among members of the Pigmented Lesion Subcommittee (PLS) of the Melanoma Prevention Working Group (MPWG) after reviewing the current evidence.
• Kim, J., Roh, E., Lee, M. H., Yu, D. H., Kim, D. J., Lim, T., Jung, S. K., Peng, C., Cho, Y., Dickinson, S., Alberts, D., Bowden, G. T., Einspahr, J., Stratton, S. P., Curiel-Lewandrowski, C., Bode, A. M., Lee, K. W., & Dong, Z. (2015). Fyn is a redox sensor involved in solar ultraviolet light-induced signal transduction in skin carcinogenesis. Oncogene.
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  Solar ultraviolet (UV) light is a major etiological factor in skin carcinogenesis, with solar UV-stimulated signal transduction inducing pathological changes and skin damage. The primary sensor of solar UV-induced cellular signaling has not been identified. We use an experimental system of solar simulated light (SSL) to mimic solar UV and we demonstrate that Fyn is a primary redox sensor involved in SSL-induced signal transduction. Reactive oxygen species (ROS) generated by SSL exposure directly oxidize Cys488 of Fyn, resulting in increased Fyn kinase activity. Fyn oxidation was increased in mouse skin after SSL exposure and Fyn-knockout mice formed larger and more tumors compared with Fyn wild-type mice when exposed to SSL for an extended period of time. Murine embryonic fibroblasts (MEFs) lacking Fyn and cells in which Fyn expression was knocked down were resistant to SSL-induced apoptosis. Furthermore, cells expressing mutant Fyn (C448A) were resistant to SSL-induced apoptosis. These findings suggest that Fyn acts as a regulatory nexus between solar UV, ROS and signal transduction during skin carcinogenesis.Oncogene advance online publication, 21 December 2015; doi:10.1038/onc.2015.471.
• Krase, I. Z., Cavanaugh, K., & Curiel-Lewandrowski, C. (2015). Treatment of Refractory Pityriasis Rubra Pilaris With Novel Phosphodiesterase 4 (PDE4) Inhibitor Apremilast. JAMA dermatology, 1-2.
• Lee, M., Lim, D. o., Kim, D., Lee, D., Shin, D., Kim, D., Kim, D., Kim, D., Jung, D., Yao, D., Kundu, D., Lee, D., Lee, D., Dickinson, D., Alberts, D., Bowden, D., Stratton, D., Curiel, D., Einspahr, D., , Bode, D., et al. (2015). Genetic ablation of caspase-7 promotes solar-simulated light-induced mouse skin carcinogenesis: the involvement of keratin-17. Carcinogenesis, 36(11), 1372-80.
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  Solar ultraviolet irradiation is an environmental carcinogen that causes skin cancer. Caspase-7 is reportedly expressed at reduced levels in many cancers. The present study was designed to examine the role of caspase-7 in solar-simulated light (SSL)-induced skin cancer and to elucidate its underlying molecular mechanisms. Our study revealed that mice with genetic deficiency of caspase-7 are highly susceptible to SSL-induced skin carcinogenesis. Epidermal hyperplasia, tumor volume and the average number of tumors were significantly increased in caspase-7 knockout (KO) mice compared with SKH1 wild-type mice irradiated with SSL. The expression of cell proliferation markers, such as survivin and Ki-67, was elevated in SSL-irradiated skin of caspase-7 KO mice compared with those observed in SSL-exposed wild-type SKH1 mouse skin. Moreover, SSL-induced apoptosis was abolished in skin from caspase-7 KO mice. Two-dimensional gel electrophoresis, followed by matrix-assisted laser desorption/ionization-time-of-flight analysis of skin tissue lysates from SSL-irradiated SKH1 wild-type and caspase-7 KO mice revealed an aberrant induction of keratin-17 in caspase-7 KO mice. Immunohistochemical analysis of skin tumors also showed an increase of keratin-17 expression in caspase-7 KO mice compared with SKH1 wild-type mice. The expression of keratin-17 was also elevated in SSL-irradiated caspase-7 KO keratinocytes as well as in human basal cell carcinomas. The in vitro caspase activity assay showed keratin-17 as a substrate of caspase-7, but not caspase-3. Overall, our study demonstrates that genetic loss of caspase-7 promotes SSL-induced skin carcinogenesis by blocking caspase-7-mediated cleavage of keratin-17.
• Marghoob, A. A., & , I. S. (2015). Standards in Dermatologic Imaging. JAMA dermatology, 151(8), 819-21.
• Moye, M. S., King, S. M., Rice, Z. P., DeLong, L. K., Seidler, A. M., Veledar, E., Curiel-Lewandrowski, C., & Chen, S. C. (2015). Effects of total-body digital photography on cancer worry in patients with atypical mole syndrome. JAMA dermatology, 151(2), 137-43.
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  Cancer worry about developing melanoma in at-risk patients may affect one's quality of life and adherence to screening. Little is known about melanoma-related worry in patients with atypical mole syndrome (AMS).
• Richtig, E., Asslaber, M., Partl, R., Avian, A., Berghold, A., Kapp, K., Preusser, M., Becker, J. C., & Curiel-Lewandrowski, C. (2015). Lack of P-glycoprotein expression in melanoma brain metastases of different melanoma types. Clinical neuropathology.
• Richtig, E., Trapp, E. M., Avian, A., Brezinsek, H. P., Trapp, M., Egger, J. W., Kapfhammer, H. P., Rohrer, P. M., Berghold, A., Curiel-Lewandrowski, C., & Demel, U. (2015). Psychological Stress and Immunological Modulations in Early-stage Melanoma Patients. Acta dermato-venereologica, 95(6), 691-5.
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  Mental stress may have a negative impact on the immune state of cancer patients, in whom immunologic surveillance is essential for survival. This study investigated the immunological response of 19 patients with early-stage melanoma and a matched control group undergoing the Determination Stress Test before surgery. Cytokine and chemokine levels and lymphocyte subpopulations were measured at baseline and post-stress test time-points. Following the stress test lower levels of interleukin (IL)-6 were observed in the melanoma group compared with healthy volunteers (p = 0.044). IL-10 increased significantly in the control group 30 min after the stress test (p = 0.002) in comparison with the melanoma group (p = 0.407). CCL5/Rantes decreased significantly in the melanoma group, whereas CD16/CD56+ natural killer cells increased in both groups, with a sharp decrease below baseline after stress in the melanoma group (p = 0.001). This pilot study shows an altered immunological response to stressors in melanoma patients.
• Tuzova, M., Conniff, T., Curiel-Lewandrowski, C., Chaney, K., Cruikshank, W., & Wolpowitz, D. (2015). Absence of full-length neurokinin-1 receptor protein expression by cutaneous T cells: implications for substance P-mediated Signaling in Cutaneous T-cell Lymphoma. Acta dermato-venereologica, 95(7), 852-4.
• Tuzova, M., Richmond, J., Wolpowitz, D., Curiel-Lewandrowski, C., Chaney, K., Kupper, T., & Cruikshank, W. (2015). CCR4+T cell recruitment to the skin in mycosis fungoides: potential contributions by thymic stromal lymphopoietin and interleukin-16. Leukemia & lymphoma, 56(2), 440-9.
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  Mycosis fungoides (MF) is characterized by skin accumulation of CCR4+CCR7- effector memory T cells; however the mechanism for their recruitment is not clearly identified. Thymic Stromal Lymphopoietin (TSLP) is a keratinocyte-derived cytokine that triggers Th2 immunity and is associated with T cell recruitment to the skin in atopic dermatitis. Interleukin-16 (IL-16) is a chemoattractant and growth factor for CD4+T cells. We hypothesized that TSLP and IL-16 could contribute to recruitment of malignant T cells in MF. We found elevated TSLP and IL-16 in very early stage patients' plasma and skin biopsies, prior to elevation in CCL22. Both TSLP and IL-16 induced migratory responses of CCR4+TSLPR+CD4+CCR7-CD31+cells, characteristic of malignant T cells in the skin. Co-stimulation also resulted in significant proliferative responses. We conclude that TSLP and IL-16, expressed at early stages of disease, function to recruit malignant T cells to the skin and contribute to their enhanced proliferation.
• Curiel-lewandrowski, C., Curiel-lewandrowski, C., Einspahr, J. G., Einspahr, J. G., Chow, H. S., Chow, H. S., Tangrea, J., Tangrea, J., Tang, J. Y., Tang, J. Y., Rezaee, M., Rezaee, M., Parnes, H. L., Parnes, H. L., Lee, A., Lee, A., Hsu, C. H., Hsu, C. H., Einspahr, J. G., , Einspahr, J. G., et al. (2014). Abstract 3248: Pilot study on the bioactivity of vitamin D in the skin after oral supplementation. Cancer Research, 74, 3248-3248. doi:10.1158/1538-7445.am2014-3248
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  Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Experimental studies suggest that vitamin D (VD) plays an important role in skin carcinogenesis. In humans, epidemiologic studies have reported mixed findings in the association between circulating vitamin D levels and skin cancer risk. We conducted a pilot clinical study to determine whether oral VD supplementation would exert any bioactivity in human skin. Methods: The study accrued twenty-five healthy individuals with serum 25-hydroxyvitamin D levels
• Curiel-lewandrowski, C., Curiel-lewandrowski, C., Einspahr, J. G., Einspahr, J. G., Stratton, S. P., Stratton, S. P., Petricoin, E. F., Petricoin, E. F., Hu, C., Hu, C., Einspahr, J. G., Einspahr, J. G., Curiel-lewandrowski, C., Curiel-lewandrowski, C., Calvert, V. S., Calvert, V. S., Bowden, G. T., Bowden, G. T., Bermudez, Y., , Bermudez, Y., et al. (2014). Abstract 3246: Mapping of functional protein pathway modulations in non-sun exposed skin of healthy volunteers using solar simulated light: A new model for pharmacodynamic testing of skin cancer chemopreventive drugs. Cancer Research, 74, 3246-3246. doi:10.1158/1538-7445.am2014-3246
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  Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Efficient secondary prevention methods for non-melanoma skin cancers are needed to supplement primary prevention in high-risk individuals. Pharmacologic effects in UV-induced keratinocyte signaling may predict efficacy of new drugs. In order to understand effects of solar light on signal transduction networks in human skin, we exposed buttocks skin of healthy volunteers to solar-simulated light (SSL) at doses 2x-3x of minimum erythemal dose (MED) using a Multiport UV Solar Simulator (Solar Light Co.). Punch biopsies (6 mm) were collected at baseline, 5 min, 1 hr, 5 hr, and 24 hr post-exposure. Biopsies were split with half fixed in formalin and half snap-frozen for Reverse Phase Protein Microarray (RPMA) analysis to identify relevant signaling networks activated by SSL exposure. 24 subjects ≥ 18 y.o. with Fitzpatrick skin type II or III, with no concurrent illness, cancer, or use of photosensitizing drugs were recruited. 12 were exposed to SSL at 2x MED, 6 at 2.5x MED, and 6 at 3x MED. The activation/phosphorylation or total levels of 128 key signaling proteins and drug targets were measured for each sample. Coordinate network-based analysis was performed on specific signaling pathways that included PI3k/Akt/mTOR, Ras/Raf/MEK/Erk, and Fyn/RSK2. Analyte levels were compared at baseline to those at 5 min, 1 hr, 5 hr, and 24 hr after SSL exposure. Unsupervised and supervised statistical analysis was used with Bonferroni multiple comparison adjustment (p < 0.01). Pathway activation maps were constructed using p values to indicate time-dependence of pathway activation. Differences in MED did not significantly affect expression, so all 24 subjects were analyzed independent of SSL dose. Most pathway modulation occurred within the first 5 hr, with cell death and apoptosis-related endpoints maximal at 24 hr. Many kinases were activated within 5 min and activity increased at 1-5 hr before reversing to baseline or lower at 24 hr. Early and sustained activation of p38/SAPK/ ERK pathways started at 5 min, continued through 5 hr and was sustained at 24 hr. Systemic AKT-mTOR pathway activation was observed from 5 min-1 hr, sustained through 5 hr, and decreased at 24 hr. EGFR-HER3 activation followed a similar pattern. COX2 expression increased at 1 hr and was sustained through 24 hr. AMPK was activated early and sustained through 24 hr since LKB1, the dominant AMPK kinase was activated within 5 min-1hr and sustained. Correlation-based network maps were generated and revealed time-dependent SSL induced pathway activation linkages. This work shows that protein pathway activation mapping of phosphorylated proteins in relevant signaling pathways can be used in future studies to determine pharmacodynamic activity of selective topical agents administered in a test area exposed to SSL to determine drug-induced modification of skin carcinogenesis pathways. Citation Format: Steven P. Stratton, Clara Curiel-Lewandrowski, Janine G. Einspahr, Valerie Calvert, Chengcheng Hu, Yira Bermudez, David S. Alberts, George T. Bowden, Emanuel F. Petricoin. Mapping of functional protein pathway modulations in non-sun exposed skin of healthy volunteers using solar simulated light: A new model for pharmacodynamic testing of skin cancer chemopreventive drugs. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3246. doi:10.1158/1538-7445.AM2014-3246
• Curiel-lewandrowski, C., Yamasaki, H., Si, C. P., Jin, X., Zhang, Y., Tuzova, M., Ryzhenko, N., Little, F., Kupper, T. S., Cruikshank, W. W., Wilson, K. J., Sullivan, B. A., Richmond, J. M., & Jones, D. R. (2014). Retraction: Loss of nuclear pro-IL-16 facilitates cell cycle progression in human cutaneous T cell lymphoma.. The Journal of clinical investigation, 124(11), 5085. doi:10.1172/jci79199
• Krupinski, E. A., Chao, J., Hofmann-Wellenhof, R., Morrison, L., & Curiel-Lewandrowski, C. (2014). Understanding visual search patterns of dermatologists assessing pigmented skin lesions before and after online training. Journal of digital imaging, 27(6), 779-85.
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  The goal of this investigation was to explore the feasibility of characterizing the visual search characteristics of dermatologists evaluating images corresponding to single pigmented skin lesions (PSLs) (close-ups and dermoscopy) as a venue to improve training programs for dermoscopy. Two Board-certified dermatologists and two dermatology residents participated in a phased study. In phase I, they viewed a series of 20 PSL cases ranging from benign nevi to melanoma. The close-up and dermoscopy images of the PSL were evaluated sequentially and rated individually as benign or malignant, while eye position was recorded. Subsequently, the participating subjects completed an online dermoscopy training module that included a pre- and post-test assessing their dermoscopy skills (phase 2). Three months later, the subjects repeated their assessment on the 20 PSLs presented during phase I of the study. Significant differences in viewing time and eye-position parameters were observed as a function of level of expertise. Dermatologists overall have more efficient search than residents generating fewer fixations with shorter dwells. Fixations and dwells associated with decisions changing from benign to malignant or vice versa from photo to dermatoscopic viewing were longer than any other decision, indicating increased visual processing for those decisions. These differences in visual search may have implications for developing tools to teach dermatologists and residents about how to better utilize dermoscopy in clinical practice.
• Malvehy, J., Hauschild, A., Curiel-Lewandrowski, C., Mohr, P., Hofmann-Wellenhof, R., Motley, R., Berking, C., Grossman, D., Paoli, J., Loquai, C., Olah, J., Reinhold, U., Wenger, H., Dirschka, T., Davis, S., Henderson, C., Rabinovitz, H., Welzel, J., Schadendorf, D., & Birgersson, U. (2014). Clinical performance of the Nevisense system in cutaneous melanoma detection: an international, multicentre, prospective and blinded clinical trial on efficacy and safety. The British journal of dermatology, 171(5), 1099-107.
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  Even though progress has been made, the detection of melanoma still poses a challenge. In light of this situation, the Nevisense electrical impedance spectroscopy (EIS) system (SciBase AB, Stockholm, Sweden) was designed and shown to have the potential to be used as an adjunct diagnostic tool for melanoma detection.
• Averbook, B. J., Lee, S. J., Delman, K. A., Gow, K. W., Zager, J. S., Sondak, V. K., Messina, J. L., Sabel, M. S., Pittelkow, M. R., Ecker, P. M., Markovic, S. N., Swetter, S. M., Leachman, S. A., Testori, A., Curiel-Lewandrowski, C., Go, R. S., Jukic, D. M., & Kirkwood, J. M. (2013). Pediatric melanoma: analysis of an international registry. Cancer, 119(22), 4012-9.
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  The management of pediatric melanoma (PM) has largely been extrapolated from adult data. However, the behavior of PM appears to differ from its adult counterparts. Therefore, an international PM registry was created and analyzed.
• Chao, J. T., Loescher, L. J., Soyer, H. P., & Curiel-Lewandrowski, C. (2013). Barriers to mobile teledermoscopy in primary care. Journal of the American Academy of Dermatology, 69(5), 821-4.
• Cranmer, L. D., Warneke, J. A., Warneke, J. A., Kang, P. T., Jeter, J. M., Hersh, E. M., Curiel, C. N., Cranmer, L. D., & Baker, A. L. (2013). Relationship of bleeding to pathologic ulceration in a primary melanoma lesion.. Journal of Clinical Oncology, 31(15_suppl), 9102-9102. doi:10.1200/jco.2013.31.15_suppl.9102
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  9102 Background: Lesion bleeding (BL) is a catalyst symptom leading to melanoma (MEL) diagnosis and is associated with adverse outcomes. The pathophysiologic significance of BL has not been elucida...
• Curiel-lewandrowski, C., Einspahr, J. G., Stratton, S. P., Saboda, K., Hu, C., Einspahr, J. G., Curiel-lewandrowski, C., Bowden, G. T., Bermudez, Y., & Alberts, D. S. (2013). Abstract 4264: PI3K/Akt/mTOR signaling modulation in solar UV-induced skin carcinogenesis.. Cancer Research, 73, 4264-4264. doi:10.1158/1538-7445.am2013-4264
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  Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the most common types of cancers. Since most BCC and SCC develop on sun-exposed areas of the body, chronic sun exposure is considered the main etiologic factor of these tumors. In vitro and in vivo studies have identified PI3K/Akt/mTOR signaling pathway as a solar light-activated pathway. However, little work has been done on studying the expression profiles of this pathway in humans. In the study herein, we evaluate the modulation of solar light-activated PI3K/Akt/mTOR signaling pathway in normal human skin and solar simulated light (SSL)-irradiated human skin to determine the expression profiles of upstream and downstream phosphorylated proteins Akt (Ser473), mTOR (Ser2448), S6 ribosomal protein (Ser235/236), and 4E-BP1 (Thr37/46). The study population consisted of individuals 18 years or older in general good health with skin types II-III. SSL irradiation at 2, 2.5, and 3 times minimal erythema dose (MED) were applied to unexposed skin. Punch biopsies were taken at baseline, 5 minutes, 1 h, 5 h, and 24 h post-irradiation and immediately fixed in 10% formalin. Tissues were evaluated by immunohistochemistry for the expression of phosphorylated proteins. Proliferating cell nuclear antigen (PCNA) and cleaved caspase 3 (Asp175) were evaluated as markers for keratinocyte proliferation and apoptosis, respectively. Induction of phosphorylated Akt was seen at 5 hours with a 2-fold increase in expression when compared to baseline. Expression of phosphorylated mTOR gradually increased with a peak at 24 hours (3-fold). Significant induction of phosphorylated S6 ribosomal protein was seen at 1 h (3-fold), 5 h (7-fold), and 24 h (10-fold) post SSL irradiation. Induction of phosphorylated 4E-BP1 was limited to the 24 h time point with an increase of 2-fold when compared to baseline. Our data corroborate in vitro and in vivo studies finding, which allow for better understanding of the expression profile patterns of phosphorylated proteins in the PI-3 kinase/Akt/mTOR pathway during exposure of physiological relevant solar-simulated light. Identification of key proteins in this pathway could lead to the use of these proteins as biomarkers and/or specific targets for the prevention and control of skin tumors. Citation Format: Yira Bermudez, Steve P. Stratton, Clara Curiel-Lewandrowski, Chengcheng Hu, George T. Bowden, Kathylynn Saboda, David S. Alberts, Janine G. Einspahr. PI3K/Akt/mTOR signaling modulation in solar UV-induced skin carcinogenesis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4264. doi:10.1158/1538-7445.AM2013-4264
• Dupont, J., Culpepper, K. S., & Curiel-Lewandrowski, C. (2013). [Red papule with collarette scale on thigh]. Der Hautarzt; Zeitschrift für Dermatologie, Venerologie, und verwandte Gebiete, 64(8), 603-5.
• Kim, C. C., Kim, E. J., Curiel-Lewandrowski, C., Marks, V., Maloney, M., & Frieden, I. J. (2013). A model in dermatology for long-distance mentoring. Journal of the American Academy of Dermatology, 68(5), 860-2.
• LaPresto, L., Cranmer, L., Morrison, L., Erickson, C. P., & Curiel-Lewandrowski, C. (2013). A novel therapeutic combination approach for treating multiple vemurafenib-induced keratoacanthomas: systemic acitretin and intralesional fluorouracil. JAMA dermatology, 149(3), 279-81.
• Loescher, L. J., Janda, M., Soyer, H. P., Shea, K., & Curiel-Lewandrowski, C. (2013). Advances in skin cancer early detection and diagnosis. Seminars in oncology nursing, 29(3), 170-81.
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  To provide an overview of 1) traditional methods of skin cancer early detection, 2) current technologies for skin cancer detection, and 3) evolving practice models of early detection.
• Curiel-Lewandrowski, C., Chen, S. C., Swetter, S. M., & , M. P. (2012). Screening and prevention measures for melanoma: is there a survival advantage?. Current oncology reports, 14(5), 458-67.
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  Controversy has emerged over the past decades regarding the value and impact of melanoma screening to detect early stage disease for improved prognosis. Those questioning the benefits of prevention efforts base their arguments on the absence of prospective, randomized studies demonstrating decreased melanoma mortality to justify the cost associated with screening and educational campaigns. For those in favor of melanoma screening, the lack of proven survival benefit is not a justification to abandon this approach, but rather a reflection of the lack of resources necessary to conduct a long-term trial. In 2009, the US Preventive Services Task Force (USPSTF)report did not recommend routine primary care screening for the general population given the absence of evidence. However, since the USPSTF report, a series of new studies are available, which support the potential benefit of screening and have the potential to significantly impact current policies regarding skin cancer screening, particularly for melanoma.
• Curiel-Lewandrowski, C., Kim, C. C., Swetter, S. M., Chen, S. C., Halpern, A. C., Kirkwood, J. M., Leachman, S. A., Marghoob, A. A., Ming, M. E., Grichnik, J. M., & , M. P. (2012). Survival is not the only valuable end point in melanoma screening. The Journal of investigative dermatology, 132(5), 1332-7.
• Curiel-Lewandrowski, C., Swetter, S. M., Einspahr, J. G., Hsu, C., Nagle, R., Sagerman, P., Tangrea, J., Parnes, H., Alberts, D. S., & Chow, H. (2012). Randomized, double-blind, placebo-controlled trial of sulindac in individuals at risk for melanoma: evaluation of potential chemopreventive activity. Cancer, 118(23), 5848-56.
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  Reduced melanoma risk has been reported with regular use of nonsteroidal anti-inflammatory drugs (NSAIDs). However, the ability of NSAIDs to reach melanocytes in vivo and modulate key biomarkers in preneoplastic lesions such as atypical nevi has not been evaluated.
• Einspahr, J. G., Calvert, V., Alberts, D. S., Curiel-Lewandrowski, C., Warneke, J., Krouse, R., Stratton, S. P., Liotta, L., Longo, C., Pellacani, G., Pellicani, G., Prasad, A., Sagerman, P., Bermudez, Y., Deng, J., Bowden, G. T., & Petricoin, E. F. (2012). Functional protein pathway activation mapping of the progression of normal skin to squamous cell carcinoma. Cancer prevention research (Philadelphia, Pa.), 5(3), 403-13.
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  Reverse phase protein microarray analysis was used to identify cell signaling derangements in squamous cell carcinoma (SCC) compared with actinic keratosis (AK) and upper inner arm (UIA). We analyzed two independent tissue sets with isolation and enrichment of epithelial cells by laser capture microdissection. Set 1 served as a pilot and a means to identify protein pathway activation alterations that could be further validated in a second independent set. Set 1 was comprised of 4 AK, 13 SCC, and 20 UIA. Set 2 included 15 AK, 9 SCCs, and 20 UIAs. Activation of 51 signaling proteins, known to be involved in tumorigenesis, were assessed for set 1 and showed that the MEK-ERK [mitogen-activated protein (MAP)/extracellular signal-regulated (ERK; MEK)] pathway was activated in SCC compared with AK and UIA, and that epidermal growth factor receptor (EGFR) and mTOR pathways were aberrantly activated in SCC. Unsupervised two-way hierarchical clustering revealed that AK and UIA shared a common signaling network activation architecture while SCC was dramatically different. Statistical analysis found that prosurvival signaling through phosphorylation of ASK and 4EBP1 as well as increased Bax and Bak expression was higher in AK compared with UIA. We expanded pathway network activation mapping in set 2 to 101 key signaling proteins, which corroborated activation of MEK-ERK, EGFR, and mTOR pathways through discovery of a number of upstream and downstream signaling molecules within these pathways to conclude that SCC is indeed a pathway activation-driven disease. Pathway activation mapping of SCC compared with AK revealed several interconnected networks that could be targeted with drug therapy for potential chemoprevention and therapeutic applications.
• Kurtzman, D., Dupont, J., Lian, F., & Curiel-Lewandrowski, C. (2012). Fatigue and lower-extremity ecchymosis in a 36-year-old woman. Scurvy. Archives of dermatology, 148(9), 1073-8.
• LaPresto, L., Cranmer, L., Erickson, C. P., Morrison, L., & Curiel-Lewandrowski, C. (2012). Erythematous annular plaques on the trunk. Archives of dermatology, 148(4), 531-6.
• Curiel-Lewandrowski, C., Nijsten, T., Gomez, M. L., Hollestein, L. M., Atkins, M. B., & Stern, R. S. (2011). Long-term use of nonsteroidal anti-inflammatory drugs decreases the risk of cutaneous melanoma: results of a United States case-control study. The Journal of investigative dermatology, 131(7), 1460-8.
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  Experimental and observational studies continue to demonstrate conflicting results regarding the role of several commonly used drugs as melanoma chemopreventive agents. This case-control study was designed to assess the associations between cutaneous melanoma (CM) and exposure to nonsteroidal anti-inflammatory drugs (NSAIDs) and statins in current users. A total of 400 CM and 600 eligible age- and gender-matched community-based controls were prospectively recruited and interviewed. We assessed participants' demographic characteristics, CM risk factors, and current and previous use of medications. Multivariable conditional logistic regression models were used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for associations between NSAIDs and/or aspirin (ASA), statin exposure, and CM risk. Half of the subjects were men (mean age 60 years). After adjusting for confounders, use of any type of NSAIDs for more than 5 years significantly reduced the risk of melanoma development compared with the low-exposure group (adjusted OR=0.57; 95% CI=0.43-0.77). Subgroup analyses showed that the observed risk reduction was primarily driven by continuous ASA use (>5 years adjusted OR=0.51, 95% CI=0.35-0.75). No significant protective effect was observed with statin exposure (OR=0.97, 95% CI=0.73-1.29). Long-term use of NSAIDs, especially ASA, is associated with a significantly decreased risk of CM development. Clinical intervention studies are warranted to further investigate the potential role of ASA and other NSAIDs as chemopreventive agents for CM.
• Curiel-Lewandrowski, C., Speetzen, L. S., Cranmer, L., Warneke, J. A., & Loescher, L. J. (2011). Multiple primary cutaneous melanomas in Li-Fraumeni syndrome. Archives of dermatology, 147(2), 248-50.
• Curiel-Lewandrowski, C., Yamasaki, H., Si, C. P., Jin, X., Zhang, Y., Richmond, J., Tuzova, M., Wilson, K., Sullivan, B., Jones, D., Ryzhenko, N., Little, F., Kupper, T. S., Center, D. M., & Cruikshank, W. W. (2011). Loss of nuclear pro-IL-16 facilitates cell cycle progression in human cutaneous T cell lymphoma. The Journal of clinical investigation, 121(12), 4838-49.
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  Cutaneous T cell lymphomas (CTCLs) represent a heterogeneous group of non-Hodgkin lymphomas that affect the skin. The pathogenesis of these conditions is poorly understood. For example, the signaling mechanisms contributing to the dysregulated growth of the neoplastic T cells are not well defined. Here, we demonstrate that loss of nuclear localization of pro-IL-16 facilitates CTCL cell proliferation by causing a decrease in expression of the cyclin dependent-kinase inhibitor p27Kip1. The decrease in p27Kip1 expression was directly attributable to an increase in expression of S-phase kinase-associated protein 2 (Skp2). Regulation of Skp2 is in part attributed to the nuclear presence of the scaffold protein pro-IL-16. T cells isolated from 11 patients with advanced CTCL, but not those from healthy controls or patients with T cell acute lymphocytic leukemia (T-ALL), demonstrated reduction in nuclear pro-IL-16 levels. Sequence analysis identified the presence of mutations in the 5' end of the PDZ1 region of pro-IL-16, a domain required for association of pro-IL-16 with the nuclear chaperone HSC70 (also known as HSPA8). HSC70 knockdown led to loss of nuclear translocation by pro-IL-16 and subsequent increases in Skp2 levels and decreases in p27Kip1 levels, which ultimately enhanced T cell proliferation. Thus, our data indicate that advanced CTCL cell growth is facilitated, at least in part, by mutations in the scaffold protein pro-IL-16, which directly regulates Skp2 synthesis.
• Curiel-lewandrowski, C., Chow, H. S., Nagle, R. B., Tangrea, J. A., Swetter, S. M., Sagerman, P., Parnes, H. L., Nagle, R. B., Hsu, C. H., Hsu, C. H., Einsphar, J., Curiel-lewandrowski, C., Chow, H. S., & Alberts, D. S. (2011). Abstract CN06-01: Phase IIa trial of sulindac in individuals at increased risk for melanoma. Cancer Prevention Research, 4. doi:10.1158/1940-6207.prev-11-cn06-01
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  Some epidemiological studies and several experimental publications suggest that regular use of non-steroidal anti-inflammatory drugs (NSAIDs) may reduce the risk of melanoma. However, specific information on the ability of NSAIDs to reach melanocytes in vivo and to modulate key biomarkers in pre-neoplastic lesions such as dysplastic nevi have not been evaluated to date. Methods: We conducted a randomized, double-blind, placebo controlled trial of sulindac in individuals at risk for melanoma to determine whether sulindac and related metabolites are bioavailable in the nevi and whether sulindac intervention has an effect on apoptosis and vascular endothelial growth factor (VEGF) expression in atypical nevi (AN). Fifty healthy subjects with ≥ 4 large (≥5 mm and Citation Information: Cancer Prev Res 2011;4(10 Suppl):CN06-01.
• Curiel-lewandrowski, C., Warneke, J. A., Hurst, C. A., Einspahr, J. G., Warneke, J. A., Stratton, S. P., Lang, J. E., Hurst, C. A., Einspahr, J. G., Dong, Z., Curiel-lewandrowski, C., Bowden, G. T., Bode, A. M., Bermudez, Y., & Alberts, D. S. (2011). Abstract 3673: Expression profile of phosphorylated proteins from the mTOR and Fyn/RSK2 signaling pathways in solar UV-induced skin carcinogenesis. Cancer Research, 71, 3673-3673. doi:10.1158/1538-7445.am2011-3673
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  Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL Chronic sun exposure is considered the main etiologic agent of non-melanoma skin cancer (NMSC). Inactivation of tumor suppressor p53 and activation of key oncogenic signaling pathways important in cell proliferation and transformation are considered crucial steps in the development of NMSC. Therefore, our overall hypothesis is that topically administered small molecule drugs can modulate specific targets in ultraviolet (UV)-induced signaling cascades resulting in attenuation or reversal of carcinogenic events in human skin. In the study herein, we evaluate the modulation of solar light-activated mTOR and Fyn/RSK2 signaling pathways in normal human skin and solar simulated light (SSL)-irradiated human skin to determine the expression profiles of upstream and downstream phosphorylated proteins p38 (Thr180/Tyr182), p44/42 MAPK (Thr202/Tyr204), histone H3 (Ser10), p90RSK (Thr359/Ser363), Akt (Ser473), mTOR (Ser2448), S6 ribosomal protein (Ser235/236), and 4E-BP1 (Thr37/46). The study population consisted of individuals 18 years or older in general good health with skin types II-III. SSL irradiation at various doses ranging from two to four times the minimal erythema dose (MED) was applied to unexposed skin. Punch biopsies were taken at baseline, 5 minutes, 1 h, 5 h, and 24 h post-irradiation and immediately fixed in 10% formalin. Tissues were evaluated by immunohistochemistry for the expression of phospho-proteins. Proliferating cell nuclear antigen (PCNA) and cleaved caspase 3 (Asp175) were evaluated as markers for keratinocyte proliferation and apoptosis, respectively. Marked SSL-induced changes in human epidermis were seen in the expression of phosphorylated histone H3, S6 ribosomal protein, and 4E-BP1 at 1 h, 5 h, and 24 h post-SSL as compared to control. A linear increase in phosphorylated p44/42 MAPK expression was observed at 1 h, 5 h, and 24 h post-SSL as compared to control. Phosphorylated Akt expression increased post-SSL, and appears dependent on duration and intensity of SSL exposure. Ultimately, the expression profile patterns of phosphorylated proteins in the mTOR and Fyn/Rsk2 pathways will be used to determine activity of new and selective chemoprevention agents being developed to target these SSL-induced skin carcinogenesis pathways. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3673. doi:10.1158/1538-7445.AM2011-3673
• Einspahr, J. G., Curiel-lewandrowski, C., Warneke, J. A., Warneke, J. A., Stratton, S. P., Prasad, A., Petricoin, E. F., Pellacani, G., Liotta, L. A., Krouse, R. S., Einspahr, J. G., Deng, J., Curiel-lewandrowski, C., Calvert, V. S., Bowden, T. G., & Alberts, D. S. (2011). Abstract 2917: Functional protein pathway activation mapping of the progression of normal skin to squamous cell carcinoma. Cancer Research, 71, 2917-2917. doi:10.1158/1538-7445.am2011-2917
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  Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL In order to identify important cell signaling derangements in squamous cell carcinoma (SCC) and its precursor actinic keratosis (AK) as a means to uncover important molecular targets and further characterize this disease, we analyzed two independent tissue study sets using Reverse Phase Protein Microarrays (RPMA). Set 1 served as a pilot as well as a means to generate candidate pathway alterations that could be further validated in a second independent sample set. Study Set 1 was comprised of 4 AK, 6 advanced SCC (≥ 2 cm), 7 non-advanced SCC, and 20 normal appearing skin samples [upper-inner arm, (UIA)]. Set 2 included15 AK, 5 advanced SCC, 4 non-advanced SCC and 20 UIA. LCM was used to isolate pure populations of epithelial cells. Fifty-one key signaling proteins and phosphorylated proteins were assessed for set 1 showing that the MEK-ERK pathway was activated in SCC compared to AK and normal skin, that EGFR was aberrantly activated in SCC, and that the mTOR pathway was highly activated in SCC. Unsupervised clustering revealed dramatic differences in SCC signaling architecture. Statistical analysis (p
• Engelhardt, C., Curiel-Lewandrowski, C., Warneke, J., & Cranmer, L. (2011). Metastatic cutaneous squamous cell carcinoma responding to erlotinib therapy. Journal of the American Academy of Dermatology, 65(1), 237-8.
• Loescher, L. J., Harris, J. M., & Curiel-lewandrowski, C. (2011). A systematic review of advanced practice nurses' skin cancer assessment barriers, skin lesion recognition skills, and skin cancer training activities.. Journal of the American Academy of Nurse Practitioners, 23(12), 667-73. doi:10.1111/j.1745-7599.2011.00659.x
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  Little is known about the skin cancer detection skills of advanced practice nurses (APNs). This systematic review of published literature seeks to describe (a) barriers to APNs' performance of skin examination, (b) APNs' ability to recognize suspicious skin lesions, and (c) APNs' skin cancer detection training activities..The Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement guided the literature search (OVID Medline, Web of Science, and CINAHL databases) and interpretation of findings. Of the 136 articles meeting criteria for selection, 12 pertaining to the purpose were selected for further review..Barriers to skin examination by APNs have been infrequently and inconsistently measured. Limited time to conduct skin examination is the most consistent barrier. APNs' ability to recognize and refer suspicious and benign lesions is inconsistent, but shows improvement after training. Few skin cancer training programs are available for APNs..Larger and more rigorously designed studies are needed to better determine APNs' barriers and facilitators to skin cancer assessment and their ability to recognize and appropriately refer potentially malignant skin lesions with a high level of sensitivity and specificity. Training to increase these skills needs to be targeted to APNs and occur at a much higher volume than current efforts.
• McKenzie, N. E., Saboda, K., Duckett, L. D., Goldman, R., Hu, C., & Curiel-Lewandrowski, C. N. (2011). Development of a photographic scale for consistency and guidance in dermatologic assessment of forearm sun damage. Archives of dermatology, 147(1), 31-6.
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  To develop a photographic sun damage assessment scale for forearm skin and test its feasibility and utility for consistent classification of sun damage.
• Richmond, J., Tuzova, M., Parks, A., Adams, N., Martin, E., Tawa, M., Morrison, L., Chaney, K., Kupper, T. S., Curiel-Lewandrowski, C., & Cruikshank, W. (2011). Interleukin-16 as a marker of Sézary syndrome onset and stage. Journal of clinical immunology, 31(1), 39-50.
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  Sézary syndrome is one of the most common forms of cutaneous T cell lymphoma (CTCL). It is characterized by skin infiltration of malignant T cells. We examined interleukin-16, a potent T cell chemoattractant and cell-cycle regulator, as a prospective marker of disease onset and stage.
• Tyo, J. S., Tyo, J. S., Morrison, L., Curiel, C., & Alenin, A. S. (2011). Hyperspectral measurement of the scattering of polarized light by skin. Proceedings of SPIE, 8160. doi:10.1117/12.895552
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  The goal of this study is to develop a spectropolarimeter for purposes of assessing polarization signatures in skin scattering on a regional scale. Prior research has that certain skin lesions have identifiable polarization signatures;1-3 however, those studies were limited to single lesion evaluation and are not convenient for screening patients with many suspicious legions. As a precursor to the future instrument, a simple actively illuminated Stokes spectropolarimeter was constructed to gather preliminary data about expected signatures and the required performance (resolution, wavelength, polarization state, etc.). This spectropolarimeter consists of a rotating retarder and a hyperspectral camera4 that scans through wavelengths by means of a Liquid Crystal Tunable Filter (LCTF). Data is captured in a serial fashion, where LCTF scans through eight wavelengths at each of the four retarder orientations. With a single acquisition taking 23 seconds to complete, it makes the issue of image registration very important. After proper alignment, the acquired images reveal that wavelength-dependent polarization signatures exist on a regional scale. In particular, it was found that polarization factors such as Degree of Linear Polarization (DoLP) tend to suppress many uninteresting skin features like wrinkles and skin texture, while capturing information that is not necessarily apparent in the intensity image.
• Curiel-lewandrowski, C., Nagle, R. B., Tangrea, J. A., Swetter, S. M., Sagerman, P., Saboda, K. L., Parnes, H. L., Nagle, R. B., Hu, C., Einsphar, J., Curiel-lewandrowski, C., & Chow, S. (2010). Abstract A66: Phase IIa placebo controlled trial of sulindac in individuals at increased risk for melanoma: Preliminary findings. Cancer Prevention Research, 3. doi:10.1158/1940-6207.prev-10-a66
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  Some epidemiological studies and several experimental publications suggest that regular use of NSAIDs may reduce the risk of melanoma. Proposed mechanisms of action include: inhibition of MAP kinase activity and nuclear translocation, reduction in the concentration of prostaglandins associated with the inhibition of VEGF and bFGF production and HIF-1α stabilization, reduction of the activation state of the VEGF and Ftl-1 genes, and inhibition of PI-3 kinase/Akt signaling pathway. However, specific information on the ability of NSAIDs to reach melanocytes in vivo and to modulate key biomarkers in pre-neoplastic lesions, such as dysplastic nevi, have not been evaluated to date. Methods: A phase IIa placebo controlled clinical intervention trial was designed with the primary end point to determine whether oral sulindac and related metabolites were present in benign nevi (BN) after an 8 week course of oral sulindac; secondary end points were included to determine whether a short exposure to sulindac had an effect on apoptosis and VEGF expression in atypical nevi (AN), as well as measurement of sulindac and metabolite levels in plasma. Exploratory objectives will evaluate the feasibility of reverse phase protein microarray to identify intervention related changes in cell signaling proteins, focusing initially on the pAKT/mTOR pathway and COX expression. Fifty healthy subjects with ≥ 4 large (≥5 mm and Results: To date, accrual has been completed and study intervention in all subjects is expected to be concluded in 09/10. The study intervention was well tolerated with some mild or moderate gastrointestinal adverse events that are possibly or probably related to the intervention. Sulindac, sulindac sulfide, sulindac sulfone concentrations were 0 — 1.4, 0 −9.07, and 0 — 6.1 µg/ml, respectively, in 41 post-intervention plasma samples analyzed to date. Sulindac, sulindac sulfide, sulindac sulfone concentrations were 0 — 5.2, 0 — 0.25, and 0 — 14.27 µg/g, respectively, in 40 postintervention BN samples. Conclusion: Current results suggest that NSAIDs, in particular sulindac and the active sulindac metabolites, can reach measurable levels in the skin, and specifically in melanocytic nevi, further supporting the need to assess the effect of this group of drugs as chemopreventive agents for melanoma. Supported by N01CN35158 from the National Cancer Institute, Division of Cancer Prevention. Citation Information: Cancer Prev Res 2010;3(12 Suppl):A66.
• Rice, Z. P., Weiss, F. J., DeLong, L. K., Curiel-Lewandrowski, C., & Chen, S. C. (2010). Utilization and rationale for the implementation of total body (digital) photography as an adjunct screening measure for melanoma. Melanoma research, 20(5), 417-21.
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  The primary objective of our study was to update the prevalence of total body photography (TBP) utilization and the rationale for its implementation as an adjunctive screening measure by academic dermatologists across the USA, and investigate the emergence of total body digital photography (TBDP). Our secondary objective was to further examine how TBP/TBDP is being incorporated into the dermatology screening examination in academic pigmented lesion clinics. A questionnaire was mailed to 113 dermatology departments across the USA. About 43% (49/113) of surveyed departments responded. TBP was used by 67% (33/49) of the respondents. Of these respondents, 33% (11/33) used TBDP alone, 33% (11/33) used TBDP in combination with nondigitally based TBP, and 33% (11/33) used nondigital TBP with print photos. The three most frequently cited reasons for the use of full-body baseline photographs were that they reduced patient anxiety, led to fewer biopsies, and helped to find melanoma early in the curable stage. Respondents who did not use full body baseline photographs cited logistical constraints as the number one reason, followed by perceived lack of utility. In conclusion, our study shows that there is a significant number of academic dermatologists using TBP/TBDP. However, this study also shows that there are conflicting beliefs among academic dermatologists concerning the efficacy of TBP/TBDP. At this point with a documented growing trend in utilization of TBP, more studies are needed to evaluate the efficacy of this screening adjunct to diagnose melanoma early and positively impact survival because of early diagnosis.
• Sekulic, A., Kim, S. Y., Hostetter, G., Savage, S., & Curiel-Lewandrwski, C. N. (2010). Loss of Inositol Polyphosphate-5-Phosphatase (INPP5A) is Associated with Development and Progression of Cutaneous Squamous Cell Carcinoma (SCC). Cancer Prev Res (Phila), 3(10), 1277-83.
• Sekulic, A., Kim, S. Y., Hostetter, G., Savage, S., Einspahr, J. G., Prasad, A., Sagerman, P., Curiel-Lewandrowski, C., Krouse, R., Bowden, G. T., Warneke, J., Alberts, D. S., Pittelkow, M. R., DiCaudo, D., Nickoloff, B. J., Trent, J. M., & Bittner, M. (2010). Loss of inositol polyphosphate 5-phosphatase is an early event in development of cutaneous squamous cell carcinoma. Cancer prevention research (Philadelphia, Pa.), 3(10), 1277-83.
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  Cutaneous squamous cell carcinoma (SCC) occurs commonly and can metastasize. Identification of specific molecular aberrations and mechanisms underlying the development and progression of cutaneous SCC may lead to better prognostic and therapeutic approaches and more effective chemoprevention strategies. To identify genetic changes associated with early stages of cutaneous SCC development, we analyzed a series of 40 archived skin tissues ranging from normal skin to invasive SCC. Using high-resolution array-based comparative genomic hybridization, we identified deletions of a region on chromosome 10q harboring the INPP5A gene in 24% of examined SCC tumors. Subsequent validation by immunohistochemistry on an independent sample set of 71 SCC tissues showed reduced INPP5A protein levels in 72% of primary SCC tumors. Decrease in INPP5A protein levels seems to be an early event in SCC development, as it also is observed in 9 of 26 (35%) examined actinic keratoses, the earliest stage in SCC development. Importantly, further reduction of INPP5A levels is seen in a subset of SCC patients as the tumor progresses from primary to metastatic stage. The observed frequency and pattern of loss indicate that INPP5A, a negative regulator of inositol signaling, may play a role in development and progression of cutaneous SCC tumors.
• Stratton, S. P., Alberts, D. S., Einspahr, J. G., Sagerman, P. M., Warneke, J. A., Curiel-Lewandrowski, C., Myrdal, P. B., Karlage, K. L., Nickoloff, B. J., Brooks, C., Saboda, K., Yozwiak, M. L., Krutzsch, M. F., Hu, C., Lluria-Prevatt, M., Dong, Z., Bowden, G. T., & Bartels, P. H. (2010). A phase 2a study of topical perillyl alcohol cream for chemoprevention of skin cancer. Cancer prevention research (Philadelphia, Pa.), 3(2), 160-9.
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  The chemopreventive and antitumor properties of perillyl alcohol (POH) that were studied preclinically indicate that topical POH inhibits both UVB-induced murine skin carcinogenesis (squamous cell tumor models) and 7,12-dimethylbenz(a)anthracene-induced murine melanoma (transgenic models involving tyrosinase-driven Ras). A previous phase 1 clinical trial in participants with normal-appearing skin showed that topical POH cream was well tolerated at a dose of 0.76% (w/w). Here, we performed a 3-month, double-blind, randomized, placebo-controlled phase 2a trial of two different doses of topical POH in individuals with sun-damaged skin. Participants applied POH cream twice daily to each dorsal forearm. Baseline and end-of-study biopsies were taken from each participant to evaluate whether the topical application of POH was effective in reversing actinic damage as evidenced by normalization of quantitative skin histopathologic scores and change in nuclear chromatin pattern as measured by karyometric analysis. There was a borderline reduction in the histopathologic score of the lower-dose POH group compared with the placebo (P = 0.1), but this was not observed in the high-dose group. However, in the high-dose group, a statistically significant reduction in the proportion of nuclei deviating from normal was observed by the use of karyometric analysis (P < 0.01). There was no statistical significance shown in the lower-dose group. No changes were observed in p53 expression, cellular proliferation (by proliferating cell nuclear antigen expression), or apoptosis in either treatment group compared with the placebo group. These results suggest that whereas our karyometric analyses can detect a modest effect of POH in sun-damaged skin, improved delivery into the epidermis may be necessary.
• Warneke, J. A., Einspahr, J. G., Bartels, P. H., Warneke, J. A., Stratton, S. P., Jeter, J. M., Hu, C., Einspahr, J. G., Curiel, C., Bartels, P. H., & Alberts, D. S. (2010). Abstract CN02-06: Phase IIB study to evaluate the safety and efficacy of topical difluoromethylornithine and topical diclofenac in the treatment of sun-damaged skin. Cancer Prevention Research, 3. doi:10.1158/1940-6207.prev-10-cn02-06
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  Difluoromethylornithine (DFMO) and nonsteroidal anti-inflammatory drugs have been shown to have a synergistic protective effect against colon cancer. As single agents, both DFMO and diclofenac have demonstrated efficacy in the treatment of actinic keratoses, the cutaneous precursors to cutaneous squamous cell carcinomas. We designed a study investigating the effects of these two medications, alone and in combination, on sun-damaged skin of the forearm. The primary objective is to determine whether a three-month course of combination therapy increases the efficacy over either agent used alone in the treatment of moderately sun-damaged skin. The primary endpoint is the change in karyometric values from skin biopsies before and after treatment. A total of 156 subjects were enrolled in the study and randomized to A: topical DFMO applied BID × 90 days; B: topical diclofenac applied QD × 90 days; or C: topical DFMO applied BID and topical diclofenac applied QD × 90 days. Planned sample size was 138 evaluable subjects to provide 80% power to detect the difference in response rate as measured by karyometric average nuclear abnormality (ANA) between the single-agent DFMO arm and the combination treatment arm at the 2.5% significance level. The results for efficacy and safety will be presented at the AACR Frontiers in Cancer Prevention meeting. Secondary biomarker and clinical endpoints will also be summarized. These findings will provide insight into the potential use of the combination of these medications as skin cancer chemopreventive agents. Citation Information: Cancer Prev Res 2010;3(12 Suppl):CN02-06.
• Hu, S., Kim, C. C., Jessup, C., Phung, T. L., & Curiel-Lewandrowski, C. (2009). Primary cutaneous melanomas seen as inflamed pigmented lesions in patients undergoing adjuvant interferon treatment: a possible diagnostic clue for physicians. Archives of dermatology, 145(5), 565-8.
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  In addition to a complete skin examination every few months, adjuvant interferon treatment is often recommended for patients with high-risk melanomas. Therefore, dermatologists play an important role in detecting multiple primary melanomas and may be required to attempt to identify the primary melanoma in patients with metastatic disease.
• Leachman, S. A., Carucci, J., Kohlmann, W., Banks, K. C., Asgari, M. M., Bergman, W., Bianchi-Scarrà, G., Brentnall, T., Bressac-de Paillerets, B., Bruno, W., Curiel-Lewandrowski, C., de Snoo, F. A., Debniak, T., Demierre, M., Elder, D., Goldstein, A. M., Grant-Kels, J., Halpern, A. C., Ingvar, C., , Kefford, R. F., et al. (2009). Selection criteria for genetic assessment of patients with familial melanoma. Journal of the American Academy of Dermatology, 61(4), 677.e1-14.
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  Approximately 5% to 10% of melanoma may be hereditary in nature, and about 2% of melanoma can be specifically attributed to pathogenic germline mutations in cyclin-dependent kinase inhibitor 2A (CDKN2A). To appropriately identify the small proportion of patients who benefit most from referral to a genetics specialist for consideration of genetic testing for CDKN2A, we have reviewed available published studies of CDKN2A mutation analysis in cohorts with invasive, cutaneous melanoma and found variability in the rate of CDKN2A mutations based on geography, ethnicity, and the type of study and eligibility criteria used. Except in regions of high melanoma incidence, such as Australia, we found higher rates of CDKN2A positivity in individuals with 3 or more primary invasive melanomas and/or families with at least one invasive melanoma and two or more other diagnoses of invasive melanoma and/or pancreatic cancer among first- or second-degree relatives on the same side of the family. The work summarized in this review should help identify individuals who are appropriate candidates for referral for genetic consultation and possible testing.
• Loescher, L. J., Crist, J. D., Cranmer, L., Curiel-Lewandrowski, C., & Warneke, J. A. (2009). Melanoma high-risk families' perceived health care provider risk communication. Journal of cancer education : the official journal of the American Association for Cancer Education, 24(4), 301-7.
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  Families with a melanoma history are at risk of melanoma. Melanoma survival improves when people are aware of their risk and ways to modify it. We explored at-risk families' perceived risk communication from healthcare providers.
• Einspahr, J., Bowden, G. T., Alberts, D. S., McKenzie, N., & Curiel, C. N. (2008). Cross-validation of murine UVB signal transduction pathways in human skin. Photochem Photobiol;, 84(2), 463-76.
• Curiel, C., Gomez, M. L., Atkins, M. B., Nijsten, T., & Stern, R. S. (2007). Association between use of non-steroidal anti-inflammatory drugs (NSAIDs) and statins and the risk of cutaneous melanoma (CM): A case-control study. Journal of Clinical Oncology, 25(18_suppl), 8500-8500. doi:10.1200/jco.2007.25.18_suppl.8500
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  8500 Background: CM accounts for more than 77% of skin cancer deaths. Chemoprevention strategies have been hampered by the lack of supporting epidemiological data. Methods: A case control study examined the association between statins and NSAIDs use and CM in people over 40 years of age. A total of 400 histologically confirmed CM cases were recruited within 3 months from diagnosis between 3/04 and 12/06. Controls included 600 individuals without history of CM matched for age, gender and neighborhood in a ratio of 1:1.5. All completed a standardized telephone questionnaire that captured demographic characteristics, CM risk factors, and drug exposure history (length and frequency of use). Odds ratios were calculated with testing for statistical significance based on Chi square analysis. Results: To date, all 400 CM cases and 547 controls have been recruited. Interview results out of 387 cases (192 F/195 M) and 505 controls (254 F/251 M) were included for data analysis. Mean age was 58.4 and 58.5 years. The ...
• Einspahr, J. G., Thomas, T. L., Saboda, K., Nickolof, B. J., Warneke, J., Curiel-Lewandrowski, C., Ranger-Moore, J., Duckett, L., Bangert, J., Fruehauf, J. P., & Alberts, D. S. (2007). Expression of vascular endothelial growth factor in early cutaneous melanocytic lesion progression. Cancer, 110(11), 2519-27.
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  A considerable body of evidence supports the concept that a significant number of cutaneous malignant melanomas progress through a precursor lesion or dysplastic melanocytic nevi (DN). Tumor angiogenesis likely plays a critical role in early development of melanoma, and intermediate biomarkers of angiogenesis could be useful as chemoprevention and prognostic markers.
• Einspahr, J. G., Thomas, T. M., Saboda, K., Nickoloff, B. J., & Curiel-Lewandrowski, C. N. (2007). Expression of VEGF and microvessel density counts in cutaneous melanocytic lesion progression. Cancer, 110(11), 2519-27.
• Li, F. P., Fletcher, J. A., Heinrich, M. C., Garber, J. E., Sallan, S. E., Curiel-Lewandrowski, C., Duensing, A., van de Rijn, M., Schnipper, L. E., & Demetri, G. D. (2005). Familial gastrointestinal stromal tumor syndrome: phenotypic and molecular features in a kindred. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 23(12), 2735-43.
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  Members of a family with hereditary gastrointestinal stromal tumors (GISTs) and a germline KIT oncogene mutation were evaluated for other potential syndrome manifestations. A tumor from the proband was analyzed to compare features with sporadic GISTs.
• Adams, A. E., Zwicker, J., Curiel, C. N., Kadin, M. E., & Falchuk, K. R. (2004). Aggressive cutaneous T-cell lymphomas after TNFalpha blockade. J Am Acad Dermatol, 51(4), 660-2.
• Curiel, C. N., Nijsten, T., & Kadin, M. (2004). Lymphomatoid papulosis in childhood: a retrospective cohort study of 35 cases. Arch Dermatol, 140(3), 306-12.
• Curiel, C. N., Wiliams, C. M., Swindells, K. J., Tahan, S. R., & Astner, S. (2004). Use of in vivo confocal microscopy in malignant melanoma: an aid in diagnosis and assessment of surgical and non-surgical therapeutic approaches. Arch Dermatol, 140(9), 1127-32.
• Curiel-Lewandrowski, C., Williams, C. M., Swindells, K. J., Tahan, S. R., Astner, S., Frankenthaler, R. A., & González, S. (2004). Use of in vivo confocal microscopy in malignant melanoma: an aid in diagnosis and assessment of surgical and nonsurgical therapeutic approaches. Archives of dermatology, 140(9), 1127-32.
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  Melanomas with poorly defined borders, lack of pigmentation, lentiginous extension, and location in cosmetically sensitive regions represent diagnostic and therapeutic challenges. Repeated surgical reexcisions are frequently required to achieve tumor-free margins. The use of reflectance mode confocal microscopy as an noninvasive method has shown to be a promising tool for diagnosing pigmented lesions in vivo.
• Nijsten, T., Curiel-Lewandrowski, C., & Kadin, M. E. (2004). Lymphomatoid papulosis in children: a retrospective cohort study of 35 cases. Archives of dermatology, 140(3), 306-12.
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  Lymphomatoid papulosis (LyP) is a rare entity, considered to be part of the spectrum of the CD30(+) cutaneous lymphoproliferative disorders. About 10% to 20% of the adult LyP patients will develop an associated lymphoid malignancy. Only a few cases of LyP have been described in children, and the risk of associated lymphoid malignancies in these patients is not known.
• Curiel-Lewandrowski, C., Venna, S. S., Eller, M. S., Cruikshank, W., Dougherty, I., Cruz, P. D., & Gilchrest, B. A. (2003). Inhibition of the elicitation phase of contact hypersensitivity by thymidine dinucleotides is in part mediated by increased expression of interleukin-10 in human keratinocytes. Experimental dermatology, 12(2), 145-52.
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  The production of immunomodulatory cytokines such as interleukin-10 (IL-10) from keratinocytes and other target cells in the skin plays a crucial role in UV-induced immunosuppression. Substantial evidence supports an association between DNA damage and immunomodulation. It is also known that small DNA fragments such as thymidine dinucleotides (pTpT) can mimic several UV-induced effects, including inhibition of the induction phase of the contact hypersensitivity response and up-regulation of tumor necrosis factor-alpha (TNF-alpha). To determine whether pTpT also induces IL-10 secretion by keratinocytes, and by inference whether IL-10 production after UV irradiation is a response to DNA damage, we compared the effects of pTpT with those of UV irradiation on primary human keratinocyte cultures. Subconfluent cultures of primary human keratinocytes were treated either with 10 micro M or 100 micro M pTpT or diluent alone, or exposed to solar-simulated light (100 J/m2 of UVB) or sham irradiated. An increase in IL-10 mRNA expression was observed 6-24 h after irradiation and at 24-48 h after treatment with pTpT. Detection of secreted IL-10 protein coincided with up-regulation of IL-10 gene expression at 48 and 72 h as determined by ELISA. Conditioned media from human keratinocytes treated with pTpT, like that from irradiated cells, significantly inhibited lymphocyte proliferation in the allogeneic-mixed lymphocyte reaction (MLR) assay. To determine whether pTpT mimics the suppressive influence of UVB on the elicitation phase of contact hypersensitivity, believed to result largely from IL-10 release, we compared the effects of topical application of pTpT with those of UVB irradiation on C57Bl/6 mice sensitized with dinitrofluorobenzene. Sensitized mice treated with pTpT or UVB irradiation showed markedly suppressed elicitation of ear-swelling responses. These results demonstrate that increased keratinocyte IL-10 mRNA level and IL-10 protein release are among the effects of pTpT and support the hypothesis that pTpT treatment triggers many of the biologic effects of UV irradiation by mimicking UV-induced DNA damage. Finally, regardless of mechanism, the data suggest that topical treatment with pTpT may provide a novel means of suppressing contact hypersensitivity or other lymphocyte-mediated reactions in skin.
• Curiel-Lewandrowski, C., & Atkins, M. B. (2001). Immunotherapeutic approaches for the treatment of malignant melanoma. Current opinion in investigational drugs (London, England : 2000), 2(11), 1553-63.
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  Clinical and laboratory observations suggest that host immunological responses may occasionally influence the course of melanoma, stimulating the investigation of immunotherapy approaches in this disease. Areas of active investigation have included recombinant cytokines, either alone or in combination with chemotherapeutic regimens or other biological response modifiers, such as vaccines, monoclonal antibodies, dendritic cells and gene therapy. To date, the benefit of these approaches in patients at high-risk of recurrence or advanced disease has been modest. Although many of these novel strategies are limited by weak antigen presentation, tumor-induced tolerance and tumor heterogeneity, it is possible that these approaches will prove more useful when given in combination.
• Curiel-Lewandrowski, C., & Demierre, M. F. (2000). Advances in specific immunotherapy of malignant melanoma. Journal of the American Academy of Dermatology, 43(2 Pt 1), 167-85; quiz 186-8.
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  Management of malignant melanoma continues to present a challenge to dermatologists, particularly in advanced cases. In light of the steady increase in the worldwide incidence and mortality rates for melanoma, better understanding of the immune mechanisms regulating melanoma progression and interaction with the host's immune system seems eminently important. New studies on the role of immune mechanisms in the pathogenesis and clinical course of melanoma have recently been published. We review the immune mechanisms involved in tumor progression and ways in which these mechanisms may be applied toward immunotherapeutic management of malignant melanoma.
• Curiel-Lewandrowski, C., Mahnke, K., Labeur, M., Roters, B., Schmidt, W., Granstein, R. D., Luger, T. A., Schwarz, T., & Grabbe, S. (1999). Transfection of immature murine bone marrow-derived dendritic cells with the granulocyte-macrophage colony-stimulating factor gene potently enhances their in vivo antigen-presenting capacity. Journal of immunology (Baltimore, Md. : 1950), 163(1), 174-83.
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  Ag presentation by dendritic cells (DC) is crucial for induction of primary T cell-mediated immune responses in vivo. Because DC culture from blood or bone marrow-derived progenitors is now clinically applicable, this study investigated the effectiveness of in vitro-generated murine bone marrow-derived DC (Bm-DC) for in vivo immunization protocols. Previous studies demonstrated that GM-CSF is an essential growth and differentiation factor for DC in culture and that in vivo administration of GM-CSF augments primary immune responses, which renders GM-CSF an attractive candidate to further enhance the effectiveness of DC-based immunotherapy protocols. Therefore, immature Bm-DC were transiently transfected with the GM-CSF gene and tested for differentiation, migration, and Ag-presenting capacity in vitro and in vivo. In vitro, GM-CSF gene-transfected Bm-DC were largely unaltered with regard to MHC and costimulatory molecule expression as well as alloantigen or peptide Ag-presenting capacity. When used for in vivo immunizations, however, the Ag-presenting capacity of GM-CSF gene-transfected Bm-DC was greatly enhanced compared with mock-transfected or untransfected cells, as determined by their effectiveness to induce primary immune reactions against hapten, protein Ag, and tumor Ag, respectively. Increased effectiveness in vivo correlated with the better migratory capacity of GM-CSF gene-transfected Bm-DC. These results show that GM-CSF gene transfection significantly enhances the capacity of DC to induce primary immune responses in vivo, which might also improve DC-based vaccines currently under clinical investigation.
• Curiel, C. N. (1998). Malignant melanoma and active specific immunotherapeutic options. Dermatology & Cosmetics, 8, 47-57.
• Curiel, C. N. (1999). Atypical fibroxanthoma vs malignant fibrohistiocytoma. Dermatology & Cosmetics, 9, 67-9.
• Curiel, C. N., Martinez, R., Pinto, V., Rosales, A., & Sanchez de Leon, R. (1995). Increase in cardiac output and PEEP as mechanism of pulmonary optimization. Rev Fisiol Esp, 51(1), 7-15.
• Pinto-Plata, V. M., Pozo-Parilli, J. C., Baum-Agay, A., Curiel, C. N., & Sanchez de Leon, R. (1995). Effect of blood pH on pulmonary artery pressure, left atrial pressure and fluid filtration rate in isolated rabbit lung. Revista Espanola de Fisiologia, 51(3), 117-23.
• Rosales, A. M., Curiel, C. N., Pluchino, S., Tristano, S., & Sanchez de Leon, R. (1994). Effect of furosemide administration in the fluid filtration rate and pulmonary artery pressure in isolated rabbit lung. Act Cient Venez, 49, 18-26.
• Sznajder, J. I., Ridge, K., Peluffo, G., Curiel, C. N., & Rutschman, D. (1994). Alveolar Na/K ATPase activity increases following mechanical ventilation induced pulmonary edema. Chest, 105(3Suppl), 116s-7.
• Curiel, R., Perez-Gonzalez, J. F., Brito, N., Zerpa, R., & Curiel, C. N. (1989). Positive inotropic effect mediated by alpha-1 adrenoceptor in intact human subjects. J Cardiovasc Pharmacol, 61(4), 603-615.

Proceedings Publications

• Zhao, J., Kose, K., Kang, D., Jain, M., Harris, U., & Curiel-lewandrowski, C. (2021). Deep learning-based denoising in spectrally-encoded confocal microscopy. In Endoscopic Microscopy XVI, 11620.
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  In this paper, we demonstrate deep learning-based denoising of high-speed (180 fps) confocal images obtained with our low-cost SECM device. The CARE network was trained with 3090 high- and low-SNR image pairs on the Google Colab platform and tested with 45 unseen image pairs. The CARE prediction showed significant increase of SSIM and PSNR, and reduction of the banding noise while maintaining the cellular details. The preliminary results show the potential of using a deep learning-based denoising approach to enable high-speed SECM imaging.
• Gong, C., Gong, C., Kulkarni, N., Kulkarni, N., Zhu, W., Zhu, W., Nguyen, C. D., Nguyen, C. D., Curiel-lewandrowski, C., Curiel-lewandrowski, C., Kang, D., & Kang, D. (2019). High-Speed Blood Flow Imaging with Scanless Confocal Microscope. In 2019 IEEE Photonics Conference (IPC).
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  We have developed a scanless confocal microscope and demonstrated high-speed cellular imaging of the human skin in vivo. Using the high imaging speed of 203 frames/sec, rapid blood flow was well visualized.
• Gong, C., Kulkarni, N., Zhu, W., Nguyen, C. D., Curiel-lewandrowski, C., & Kang, D. (2019). Low-cost, high-speed near-infrared confocal microscope. In Biophotonics Congress: Optics in the Life Sciences Congress 2019 (BODA,BRAIN,NTM,OMA,OMP).
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  We developed a low-cost, high-speed near infrared confocal microscope. Material cost was approximately $5,000. In vivo confocal images of human skin acquired at 203 frame/sec clearly visualized cellular features, including keratinocytes and melanocytes.
• Nguyen, C. D., Gong, C., Kulkarni, N., Zhu, W., Curiel-lewandrowski, C., & Kang, D. (2019). Light sheet microscopy of human skin in vivo. In Biophotonics Congress: Optics in the Life Sciences Congress 2019 (BODA,BRAIN,NTM,OMA,OMP).
• Curiel, C. N., Einspahr, J. G., Petricoin III, E. F., Bermudez, Y., Hu, C., Alberts, D. S., Bowden, T., Saboda, K., Calvert, V., Liotta, L., & Stratton, S. P. (2013, May). Functional Protein Pathway Activation Mapping of Normal Skin exposed to Solar Simulated Light. In International Investigative Dermatology.
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  Janine G. Einspahr, Clara Curiel-Lewandrowski, Emanuel F. Petricoin III, Yira Bermudez, ChengCheng Hu, David S. Alberts, G. Timothy Bowden, Kathylynn Saboda, Valerie Calvert, Lance Liotta, Steven P Stratton. Functional Protein Pathway Activation Mapping of Normal Skin exposed to Solar Simulated Light. 2012, International Investigative Dermatology. May 2013. Copenhagen, Denmark
• Curiel, C. N., Legat, F. J., Pellecani, G., Hofer, A., Arzberger, E., & Hofmann-Wellenhof, R. (2013, May). Reflectance Confocal Microscopy for the Monitoring of Actinic Keratoses Undergoing Photodynamic Therapy. In International Investigative Dermatology, 133.
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  Curiel-Lewandrowski, C; Legat FJ; Pellecani G; Hofer A; Arzberger E; Hofmann-Wellenhof R.Reflectance Confocal Microscopy for the Monitoring of Actinic Keratoses Undergoing Photodynamic Therapy. 2013, International Investigative Dermatology. May 2013. JID Volume 133, Issue S1 S179. Copenhagen, Denmark
• Curiel, C. N. (2011, May). Crosstalk between UV-induced PI-3 kinase/Akt/mTOR and Fyn/RSK2 signaling pathways: Implications in skin carcinogenesis. In Journal of Investigative Dermatology.
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  (A530) Crosstalk between UV-induced PI-3 kinase/Akt/mTOR and Fyn/RSK2 signaling pathways: Implications in skin carcinogenesis. Journal of Investigative Dermatology; 2011. Society of Investigative Dermatology; May 2011; Phoenix, AZ
• Curiel, C. N., Swetter, S. M., Einsphar, J., Hu, C. C., Saboda, K., Nagle, R., Sagerman, P., Tangrea, J., Parnes, H., & Chow, H. H. (2011, May). Effect of oral sulindac on biomarkers of drug bioavailability and carcinogenesis in melanocytic nevi--A double-blind, randomized, placebo-controlled trial. In Society of Investigative Dermatology.
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  (A773) Curiel-Lewandrowski C, Swetter SM, Einsphar J, Hu CC, Saboda K, Nagle R, Sagerman P, Tangrea J, Parnes H, Chow HHS. Effect of oral sulindac on biomarkers of drug bioavailability and carcinogenesis in melanocytic nevi--A double-blind, randomized, placebo-controlled trial. Journal of Investigative Dermatology; 2011. Society of Investigative Dermatology; May 2011; Phoenix, AZ
• Curiel-Lewandrowski, C. N., LaPresto, L., Hu, C. C., Saboda, K., Krutszch, M., Nagle, R., & Einspahr, J. (2011, May). Correlation between VEGF-A, VEGFR-1, pAkT, and pErk expression in melanocytic lesions and degree of histological atypia. In Society of Investigative Dermatology.
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  (A767) Curiel-Lewandrowski C, LaPresto L, Hu CC, Saboda K, Krutszch M, Nagle R, Einspahr J. Correlation between VEGF-A, VEGFR-1, pAkT, and pErk expression in melanocytic lesions and degree of histological atypia. Journal of Investigative Dermatology; 2011. Society of Investigative Dermatology; May 2011; Phoenix, AZ
• Koch, S., Newton, C., Yee, G., Silvis, N., Curiel-Lewandrowski, C. N., & Harris, R. (2011, October). Melanoma in Arizona: Decreasing or Under-Reported?. In Tucson Dermatological Society Annual Meeting.
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  Koch S, Newton C, Yee G, Silvis N, Curiel-Lewandrowski C, Harris R. Melanoma in Arizona: Decreasing or Under-Reported? Tucson Dermatological Society Annual Meeting. October, 2011. Tucson, AZ
• Coleman King, S., Veledar, E., Rice, Z., Seidler, A., Curiel-Lewandrowski, C. N., & Chen, S. (2010, May). Cancer worry (CW) in Atypical Mole Syndrome (AMS) patients utilizing Total Body Digital Photography(TBDP): Does previous history of melanoma (MM) matter?. In Journal of Investigative Dermatology, 130, S65.
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  (A389) Coleman King S, Veledar E, Rice Z, Seidler A, Curiel-Lewandrowski C, Chen S; Cancer worry (CW) in Atypical Mole Syndrome (AMS) patients utilizing Total Body Digital Photography(TBDP): Does previous history of melanoma (MM) matter?; Journal of Investigative Dermatology; 2010;130:S65; Society of Investigative Dermatology; May 2010; Atlanta, GA
• Curiel, C. N., Swetter, S., Einsphar, J., Hu, C. C., Saboda, K., Nagle, R., Sagerman, P., Tangrea, J., Parnes, H., & Chow, S. (2010, November). Phase IIa placebo controlled trial of sulindac in individuals at increased risk for melanoma-preliminary findings. In AACR Frontiers meeting.
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  (A66) Curiel-Lewandrowski C, Swetter S, Einsphar J, Hu CC ,Saboda K ,Nagle R, Sagerman P, Tangrea J, Parnes H, Chow S; Phase IIa placebo controlled trial of sulindac in individuals at increased risk for melanoma-preliminary findings. 2010 AACR Frontiers meeting. Nov 7-10,2010; Philadelphia, PA
• Gomez, M. L., Saboda, K., Kadin, M., Wang, H., & Curiel-Lewandrowski, C. N. (2010, September). Lymphomatoid Papulosis: Features From A United States Case Registry. In First World Congress of Cutaneous Lymphomas.
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  Gómez ML, Saboda K, Kadin M, Wang H, Curiel-Lewandrowski C; Lymphomatoid Papulosis: Features From A United States Case Registry; First World Congress of Cutaneous Lymphomas; September 22-25, 2010; Chicago, IL
• Calvert, V., Longo, C., Einsphar, J., Deng, J., & Curiel-Lewandrowski, C. N. (2009, April). Protein Network Analysis of SCC Reveals the AK-SCC Transition Occurs Through EGFR-driven Signaling Through MAPK/AKT/mTOR. In AACR 100th Annual Meeting.
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  (A4204)CalvertV, Longo C, Einsphar J, Deng J, Curiel-Lewandrowski C et al; Protein Network Analysis of SCC Reveals the AK-SCC Transition Occurs Through EGFR-driven Signaling Through MAPK/AKT/mTOR; AACR 100th Annual Meeting; April 18-22, 2009; San Diego, CA
• Curiel, C. N., & Einsphar, J. (2009, May). Positive correlation between VEGF-A expression in melanocytic lesions and degree of histological atypia. In Society for Investigative Dermatology, 129, S8.
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  (A43) Curiel-Lewandrowski C, Einsphar J; Positive correlation between VEGF-A expression in melanocytic lesions and degree of histological atypia; Journal of Investigative Dermatology;2009;129:S8;Society for Investigative Dermatology; May 9, 2009; Montreal, Canada.
• Curiel, C. N., Gomez, M. L., Nijsten, T., Atkins, M. B., & Correa, L. M. (2008, May). Long term use of aspirin but not statins is associated with decreased risk of cutaneous melanoma: A case controlled study. In International Investigative Dermatology Annual Meeting, 128, S84.
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  (A503) Curiel-Lewandrowski C, Gomez ML, Nijsten T, Atkins MB, Correa LM et al; Long term use of aspirin but not statins is associated with decreased risk of cutaneous melanoma: A case controlled study; Journal of Investigative Dermatology; 2008;128:S84; International Investigative Dermatology Annual Meeting; May 17, 2008; Kyoto, Japan.
• Curiel, C. N., Pressley, Z., Chen, S., & DeLong, L. (2008, February). Total Body Digital Photography in Patients with Atypical Mole Syndrome: Predictors of reduction in Melanoma Worry and Distress. In J Am Acad Dermatol, 58, AB 102.
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  (A P2100) Pressley Z, Curiel-Lewandrowski C, Chen S, DeLong L; Total Body Digital Photography in Patients with Atypical Mole Syndrome: Predictors of reduction in Melanoma Worry and Distress; J Am Acad Dermatol; 2008;58(2):AB 102; American Academy of Dermatology, 66th Annual Meeting; February 1-5, 2008; San Antonio, TX
• Curiel-Lewandrowski, C. N., Gomez, M. L., Atkins, M. B., Nijsten, T., & Stern, R. S. (2007, June). Association between use of non-steroidal anti-inflammatory drugs (NSAIDS) and statins and the risk of cutaneous melanoma (CM): a case-control study JCO. In ASCO meeting, 25, 18S.
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  (A8500) Curiel-Lewandrowski, C, Gomez ML, Atkins MB, Nijsten T, Stern RS; Association between use of non-steroidal anti-inflammatory drugs (NSAIDS) and statins and the risk of cutaneous melanoma (CM): a case-control study; JCO; 2007;25:18S;(June supp); ASCO meeting; June 3-5, 2007; Chicago, IL
• Gomez, M. L., Kadin, M., Nijsten, T., Ranger-Moore, J., & Curiel-Lewandrowski, C. N. (2007, February). Increased prevalence of thyroiditis in lymphomatoid papulosis patients. In J Am Acad Dermatol, 56, AB140.
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  (A P2105) Gómez ML, Kadin M, Nijsten T, Ranger-Moore J, Curiel-Lewandrowski C; Increased prevalence of thyroiditis in lymphomatoid papulosis patients; J Am Acad Dermatol; 2007;56(2): AB140; American Academy of Dermatology 65th Annual Meeting; February 2-6, 2007; Boston, MA
• Gomez, M. L., Kadin, M., Nijsten, T., Ranger-Moore, J., & Curiel-Lewandrowski, C. N. (2007, March). Increased prevalence of autoimmune thyroiditis in lymphomatoid papulosis patients. In The Immunology and Skin Disease 2007 International Conference.
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  Gómez ML, Kadin M, Nijsten T, Ranger-Moore J, Curiel-Lewandrowski C; Increased prevalence of autoimmune thyroiditis in lymphomatoid papulosis patients; The Immunology and Skin Disease 2007 International Conference; March 22, 2007; Boston, MA
• Pressley, Z., DeLong, L., Weiss, F., Curiel-Lewandrowski, C. N., & Chen, S. (2007, May). Utilization of total body digital photography as an adjust screening measure in melanoma. In Journal of Investigative Dermatology, 127, S146.
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  (A876) Pressley Z, DeLong L, Weiss F, Curiel-Lewandrowski C, Chen S; Utilization of total body digital photography as an adjust screening measure in melanoma; Journal of Investigative Dermatology; 2007;127:S146; Society of Investigative Dermatology; May 10-12,2007; Los Angeles, CA
• Pressley, Z., Delong, L., Curiel-Lewandrowski, C. N., & Chen, S. (2007, Spring). Quality of life and cancer anxiety impact of total body digital photography in patients with atypical mole syndrome. In J Am Acad Dermatol, 56, P2203.
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  (A114) Pressley Z, Delong L, Curiel-Lewandrowski C, Chen S; Quality of life and cancer anxiety impact of total body digital photography in patients with atypical mole syndrome; J Am Acad Dermatol; 2007;56:P2203.
• Seidler, A., Curiel-Lewandrowski, C. N., Pressley, Z., DeLong, L., & Chen, S. (2007, May). Assessment of cancer worry in patients with high-risk melanoma phenotypes. In Journal of Investigative Dermatology, 127, S151.
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  (A902) Seidler A, Curiel-Lewandrowski C, Pressley Z, DeLong L, Chen S; Assessment of cancer worry in patients with high-risk melanoma phenotypes; Journal of Investigative Dermatology; 2007;127:S151; Society for Investigative Dermatology; May 10-12, 2007; Los Angeles, CA
• Curiel, C. N., Yamasaki, H., Rhangdale, S., & Cruikshank, W. W. (2006, May). Aberrant pro-IL 16 expression in stage III and IV cutaneous T-cell lymphoma. In Journal of Investigative Dermatoloy, 124, A92.
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  (A550) Curiel-Lewandrowski C, Yamasaki H, Rhangdale S, and Cruikshank WW; Aberrant pro-IL 16 expression in stage III and IV cutaneous T-cell lymphoma; Journal of Investigative Dermatoloy;2005;124(4):A92; Society for Investigative Dermatology; May 3-6,2005; St. Louis, MO.
• Einspahr, J. G., Thomas, T. M., Saboda, K., Nickoloff, B. J., & Curiel-Lewandrowski, C. N. (2006, May). Expression of VEGF and microvessel density counts in cutaneous melanocytic lesion progression. In Society for Investigative Dermatology.
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  Einspahr JG, Thomas TM, Saboda K, Nickoloff BJ, Curiel-Lewandrowski C et al; Expression of VEGF and microvessel density counts in cutaneous melanocytic lesion progression; Society for Investigative Dermatology; May 3-6, 2006; Philadelphia, PA
• Thomas, T. L., Bozzo, P., Alberts, D. S., Curiel-Lewandrowski, C. N., & Saboda, K. (2006, May). Biomarkers of angiogenesis in progression from dysplastic nevi to malignant melanoma. In Journal of Investigative Dermatology, 126.
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  (A24) Thomas TL, Bozzo P, Alberts DS, Curiel-Lewandrowski C, Saboda K et al; Biomarkers of angiogenesis in progression from dysplastic nevi to malignant melanoma; Journal of Investigative Dermatology;2006;126:4; Society for Investigative Dermatology; May 3-6, 2006; Philadelphia, Pa
• Wu, B. P., Correa, L. M., Tahan, S. R., Gomez, M. L., & Curiel-Lewandrwoski, C. N. (2005, May). Histologic features of positive lymph nodes in malignant melanoma of the head and neck. In Journal of Investigative Dermatology, 124, A151.
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  (A906) Wu BP, Correa LM, Tahan SR, Gomez ML, Curiel-Lewandrowski C et al; Histologic features of positive lymph nodes in malignant melanoma of the head and neck; Journal of Investigative Dermatology; 2005;124(4):A151;Society for Investigative Dermatology; May 3-6, 2005; St. Louis, MO.
• Curiel-Lewandrowski, C. N., Yamasaki, H., & Cruikshank, W. W. (2003, April). Deficient pro-IL 16 expression in cutaneous T-cell lymphoma. In J Inv Dermatol, 121, 117.
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  (A701) Curiel-Lewandrowski C, Yamasaki H, and Cruikshank WW; Deficient pro-IL 16 expression in cutaneous T-cell lymphoma; J Inv Dermatol;2003;121(1):117; Society of Investigative Dermatology; April 2003
• Curiel, C. N., & Slater-Freedberg, J. (2000, March). Metastatic malignant fibrous histiocytoma mimicking atypical fibrous xanthoma. In American Academy of Dermatology 58th Annual Meeting.
• Curiel, C. N., Venna, S., Eller, M. S., Cruikshank, W., & Cruz, P. D. (2000, May). Thymidine Dinucleotides Induce Expression of IL-10 in Primary Human keratinocytes. In Society of Investigative Dermatology, 114, 783.
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  (A194) Curiel-Lewandrowski C, Venna S, Eller MS, Cruikshank W, Cruz PD Jr et al; Thymidine Dinucleotides Induce Expression of IL-10 in Primary Human keratinocytes; J Inv Dermatol;2000;114(4):783; Society of Investigative Dermatology; May 10-14,2000; San Francisco, CA
• Eller, M. S., Hadshiew, I. M., Puri, N., Curiel-Lewandrowski, C. N., & Venna, S. (2000, May). The single Stranded Telomeric DNA Induces DNA Damage Responses. In J Inv Dermatol, 114, 756.
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  (A37) Eller MS, Hadshiew IM, Puri N, Curiel-Lewandrowski C, Venna S et al; The single Stranded Telomeric DNA Induces DNA Damage Responses; J Inv Dermatol; 2000;114(4):756; Society of Investigative Dermatology; May 10-14, 2000;Chicago,IL
• Curiel-Lewandrowski, C. N., Stefanato, C. M., & Travers, R. (1999, March). Proteus syndrome and the many faces of hamartomatous malformations. In American Academy of Dermatology 57th Annual Meeting.
• Curiel, C. N., Gonzalez, S., Acosta, J., Alcaraz, M., & Diaz, F. (1998, Spring). Clotrimazole blocks cell cycle progression in G1 by depletion of calcium stores and differential inhibition of protein synthesis. In International Society for Investigative Dermatology.
• Curiel, C. N., Schmidt, W., Granstein, R. D., Schwarz, T., & Grabbe, S. (1996, June). Modulation of antigen presentation by transfection of dendritic cells with GM-CSF. In ASBNIB/ASIEP/AAI Joint Meeting.
• Curiel, C. N., Moran, M., Granstein, R. D., & Kochevar, I. (1995, May). Tropoelastin quantitation PCR in the study of the photoaging phenomena. In Wellman Laboratory of Photomedicine Series.
• Khurshid, A., Peluffo, G., Curiel, C. N., Ridge, K., & Sznajder, J. I. (1993, May). Transcription factors in alveolar type 2 cells, isolated from hyperoxic rats. In ALA/ATS International Conference.
• Curiel, C. N., Martinez, R., Pinto, V., Rosales, A. M., & Sanchez de Leon, R. (1991, July). Effect of cardiac output and PEEP on pulmonary shunt in isolated rabbit lung. In VII Latin-American Congress of Physiology.
• Curiel, C. N., Martinez, R., Pinto, V., & Sanchez de Leon, R. (1989, November). Blood flow modification on pulmonary shunt in isolated rabbit lung. In 3rd Venezuelan Congress of Critical care Medicine.
• Curiel, C. N., Pinto, V., Poses, J. C., & Sanchez de Leon, R. (1989, November). Effect of pulmonary artery pH on pressure and fluid filtration rate in isolated rabbit lung. In 3rd Venezuelan Congress of Critical Care Medicine.
• Curiel, R., Zerpa, R., Brito, N., Curiel, C. N., & Cubeddu, L. (1987, July). Positive inotropic effect of metoxamin in human heart. In 1st Congress of the Venezuelan Pharmacology Society.

Presentations

• Curiel, C. N., Calvert, V., Petricoin, E., Roe, D., Saboda, K., Yozwiak, M., Krutzsch, M., & Dickinson, S. E. (2019, Spring). Increased PD-L1 expression in human skin acutely and chronically exposed to UV irradiation.. Society for Investigational Dermatology. Chicago, IL.
• Curiel, C. N. (2010, October). Pan-Pacific Skin Cancer Consortium. Telemedicine and Imaging Technology at the University of Arizona.
• Curiel, C. N. (2009, April). Skin Cancer Detection for Medical Oncologists. Weekly seminars/Medical Oncology and radiation Oncology fellows. Tucson, AZ: University of Arizona.
• Curiel, C. N. (2009, December). Advanced Imaging Technology Transfer in Dermatology. Medicine Grand Rounds. Tucson, AZ: University of Arizona.
• Curiel, C. N. (2009, October). Non-Steroidal Anti-Inflammatory Drugs and Risk of Skin Cancer. Cancer Prevention and Control Grand Rounds. Tucson, AZ.
• Curiel, C. N. (2009, October). Optical Imaging and Diagnosis of Melanoma: Where we are today and where we may be tomorrow. Tucson Dermatological Society. Tucson, AZ.
• Curiel, C. N. (2007, February). Atypical nevi patients and associated risk for the development of melanoma. Cancer Prevention and Control Seminar. Tucson, AZ: University of Arizona.
• Curiel, C. N. (2006, Spring). A practical approach to the evaluation of atypical nevi patients. Medicine Grand Rounds. University of Arizona. Tucson, AZ.
• Curiel, C. N. (2005, spring). Cutaneous T-cell lymphoma. University of Arizona. Tucson, AZ.
• Curiel, C. N. (2005, spring). Dermato-Pharmacology series. University of Arizona. Tucson, AZ.
• Curiel, C. N. (2005, spring). Skin Cancer Overview. Internal Medicine Residents/University of Arizona. Tucson, AZ..
• Curiel, C. N. (2004, Spring). A practical approach to the management of atypical nevi patients. Dermatology Grand Rounds/University of Arizona. Tucson, AZ.
• Curiel, C. N. (2004, Spring). Dermato-Epidemiology series. University of Arizona. Tucson, AZ.
• Curiel, C. N. (2004, Spring). Dermatology Residents Journal Club. Harvard Medical School. Boston, MA.
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  2002-2004
• Curiel, C. N. (2003, spring). Skin Cancer Overview. Internal Medicine Residents. Beth Israel Deaconess Medical Center. Boston, MA.
• Curiel, C. N. (2001, Spring). Cutaneous T-cell lymphoma. Boston University. Boston, MA..

Poster Presentations

• Kirschnerova V, V., Vaishampayan, P., Khawam, M., Curiel, C. N., Wondrak, G. T., & Dickinson, S. E. (2021, April). TLR4 expression as a determinant of EMT and stress response gene expression in UV exposed human keratinocytes.. AACR Annual Meeting. Virtual.
• Curiel, C. N., Krutzsch, M., Yozwiak, M., Saboda, K., Roe, D., & Dickinson, S. E. (2019, Spring). Increased PD-L1 and CD47 expression in high-risk cutaneous squamous cell carcinomas.. Society for Investigational Dermatology Conference. Chicago, IL.
• Dickinson, S. E., & Curiel-Lewandrowski, C. (2017, April). A novel strategy for topical photochemoprevention: Pharmacological TLR4 antagonism blocks non-melanoma skin cancer. 76th Annual Meeting Society of Investigative Dermatology.
• Dickinson, S. E., & Curiel-Lewandrowski, C. (2017, April). Pharmacological TLR4 antagonism using topical resatorvid blocks solar UV-induced skin tumorigenesis in SKH-1 mice. American Association of Cancer Research. Washington, DC.
• Curiel-Lewandrowski, C., & Trofymenko, O. (2016, May). The influence of health insurance status on stage at diagnosis of cutaneous melanoma. 75th Annual Meeting Society of Investigative Dermatology. Scottsdale, AZ.

Reviews

• Vaishampayan, P., Curiel-Lewandrowski, C., & Dickinson, S. E. (2023. Review: PD-L1 as an emerging target in the treatment and prevention of keratinocytic skin cancer(pp 52-61).
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  Recent advances in the understanding and targeting of immune checkpoints have led to great progress in immune therapies against many forms of cancer. While many types of immune checkpoints are currently targeted in the clinic, this review will focus on recent research implicating the programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) axis as an emerging focus for the treatment of keratinocytic tumors. PD-L1 is of particular interest in nonmelanoma skin cancer (NMSC), as it is not only upregulated in these tumors but is stimulated by environmental ultraviolet exposure. This response may also make PD-L1 an excellent target for photochemoprevention using topically applied small molecule inhibitors. Here, we summarize recent investigations on PD-L1 expression and clinically relevant immune checkpoint inhibitor treatment in cutaneous squamous cell carcinoma, basal cell carcinoma, and head and neck squamous cell carcinoma, as well as small molecule agents targeting PD-L1 that may be useful for clinical development aiming at treatment or prevention of NMSC.
• Curiel, C. N., Chen, S. C., & Swetter, S. M. (2012. Melanoma Prevention Working Group-Pigmented Skin Lesion Sub-Committee. Screening and prevention measures for melanoma: is there a survival advantage?(pp 458-67).
• Loescher, L. J., Harris, J. M., & Curiel-Lewandrowski, C. (2011. A systematic review of advanced practice nurses' skin cancer assessment barriers, skin lesion recognition skills, and skin cancer training activities(pp 667-73).
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  Little is known about the skin cancer detection skills of advanced practice nurses (APNs). This systematic review of published literature seeks to describe (a) barriers to APNs' performance of skin examination, (b) APNs' ability to recognize suspicious skin lesions, and (c) APNs' skin cancer detection training activities.
• Curiel, C. N. (2008. Faculty 1000.
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  Reviewer 2007-2008 http://www.f1000biology.com

Other Teaching Materials

• Curiel-Lewandrowski, C. N., & Kim, C. (2009. Clinical Care Options in Oncology. Non-Melanoma Skin Cancer and Cutaneous Lymphoma sections.
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  Clinical Care Options in Oncology. Non-Melanoma Skin Cancer and Cutaneous Lymphoma sections. 2009-present. Kim C and Curiel-Lewandrowski C. http://www.clinicaloptions.com/Oncology.aspx
• Curiel, C. N. (2008. Methods of Biopsy: Mohs micrographic surgery vs. standard resection for melanoma in situ and the value of Imiquimod. Melanoma Care Coalition.
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  Methods of Biopsy: Mohs micrographic surgery vs. standard resection for melanoma in situ and the value of Imiquimod. Curiel-Lewandrowski C. Melanoma Care Coalition. 2008. http://www.melanomacare.org/
• Curiel, C. N. (2005. Skin Cancer Education for Primary Care Physicians. Medical Direction. Products- Skin Cancer Education for Primary Care.
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  2. Skin Cancer Education for Primary Care Physicians. Curiel-Lewandrowski C. Medical Direction. Products- Skin Cancer Education for Primary Care. 2005-present. http://www.md-inc.com/Products/product_details.cfm?mm=2&sm=4014&courseno=1778
• Curiel, C. N. (2003. Risk factors for the development of melanoma. Section Adult Primary Care and Internal Medicine.
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  1. UpToDate: Curiel-Lewandrowski C. Risk factors for the development of melanoma. 2003-present. Section Adult Primary Care and Internal Medicine. http://www.uptodate.com/home/clinicians/toc.do?tocKey=table_of_contents/-1/16

Others

• Curiel, C. N. (2018, May). KVOA on Skin cancer/Melanoma awareness month.
• Curiel, C. N. (2017, June 1). Evaluation of Pathway Modulation by Raf, MEK, & Kinase Inhibitors. Clinical Trials.gov.
• Curiel, C. N. (2017, May 1). Proposed Technical Guidelines for the Acquisition of Clinical Images of Skin-related conditions. The JAMA Network.
• Curiel, C. N. (2017, May 3). KVOA on Skin Cancer/Melanoma awareness month. Interview.
• Curiel, C. N. (2016, May). KVOA on Skin cancer/Melanoma awareness month.
• Curiel, C. N., Cranmer, L., & Kurtzman, D. (2016, January). A Phase II Study of Vemurafenib Combined with Acitretin in Patients with Advanced Melanoma Protocol 22467.. Completed.
• Curiel, C. N., Kadin, M., Gomez, M. L., & Wong, E. (2016, January). Lymphomatoid papulosis and autoimmune disease: A nested case control study.
• Janda, J., Blohm-Mangone, K., Burkett, N., Einspahr, J. G., Alberts, D. S., Dong, Z., Bode, A. M., Curiel, C. N., Wondrak, G. T., & Dickinson, S. E. (2016, May). TLR4 as a novel molecular target for non-melanoma skin cancer prevention.. Soc. Invest. Derm. #85,.
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  Abstract for poster presented at a conference.
• Curiel, C. N. (2008, December). UA News. Press release on Raytheon/UA imaging study.
  More info

  UA News. Press release on Raytheon/UA imaging study. http://uanews.opi.arizona.edu/node/23075
• Curiel, C. N. (2015, June). Characterization of VEGF, p-AKT, PTEN, and HIF-1alpha expression in atypical melanocytic lesions.
• Curiel, C. N. (2015, June). Melanoma Rates rising among children.
  More info

  Media outreach. Melanoma Rates rising among children. With Kristi Tedesco. KVOA News http://www.kvoa.com/global/story.asp
• Curiel, C. N., Bermudez, Y., Stratton, S., Warneke, J., Hu, C., Bowden, G., Dong, Z., Bode, A., Saboda, K., Brooks, C., Petricoin, E., Hurst, C., Alberts, D., & Einsphar, J. (2015, January). Biomarkers of Solar Exposure and Therapeutic Targets for the Chemoprevention of Squamous Cell Carcinoma of the Skin.
• Curiel, C. N., Sligh, J., & Morrison, L. (2015, January). A Placebo Controlled Double-Blinded Study to Evaluate the Efficacy of vismodegib as Chemoprevention of New BCC Development in High Risk Subjects Protocol ML 28585. Completed.
• Curiel, C. N., Sligh, J., & Morrison, L. (2015, January). A Prospective Observational Study of Treatment Patterns and Effectiveness and Safety Outcomes in Advanced Basal Cell Carcinoma and Basal Cell Carcinoma Nevus Syndrome Patients Protocol ML28296:. Completed.
• Curiel, C. N., Stratton, S., & Einspahr, J. (2015, January). Pilot Study to Evaluate the Signaling Pathway Modulation Demonstrated by Raf, MEK, and Tyrosine Kinase Inhibitors Before and After Acutely Exposing Human Skin to Solar Simulated Light. Open for enrollment.
• Curiel, C. N., Dickinson, S., Stratton, S., Einspahr, E., & Alberts, D. (2014, February). Effect of Sulphorapahe in human skin following acute solar simulated light exposure. Analysis phase.
• Curiel, C. N., Kim, C. C., Lee, S. J., Swetter, S. M., Chen, S. c., Halpern, A. C., Kirkwood, J. M., Leachman, S., Marghoob, A. A., Ming, M. E., & Grichnik, J. M. (2014, June). Risk of melanoma development and determination of who is most likely to benefit from routine screening.
• Curiel-Lewandrowski, C. N., Arzberger, E., Pellacani, G., Ulrich, M., Cheng-Cheng, H. u., Saboda, K., & Hofmann-Wellenhof, R. (2013, summer). Role of reflectance confocal microscopy in the monitoring of therapeutic interventions. Analysis phase.
• Curiel-Lewandrowski, C. N., Gomez, M. L., & Kadin, M. (2012, June). Lymphomatoid papulosis prevalence in middle age women and the role of michrochinerism.
• Curiel, C. N. (2010, March). Interview: KVOA on skin cancers outnumber other cancers combined.
  More info

  http://www.kvoa.com/news/skin-cancers-outnumber-other-cancers-combined
• Curiel, C. N. (2010, May). Experts torn on effectiveness of SLNB in early melanoma. Dermatology Times.
• Curiel, C. N. (2009, February). Melanoma Prevention: Dermatology Times.
• Curiel, C. N. (2009, May). Reducing risks: Systemic retinoids useful for nonmelanoma skin cancer: Dermatology Times.
• Curiel, C. N. (2008, December). Interview: KOLD TV on Raytheon/ UA imaging study with SFAZ.
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  http://www.kold.com/Global/story.asp?s=9534538
• Curiel, C. N. (2008, October). Media Outreach. KUAT/PBS TV on Skin Cancer.
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  Web Link http://tv.azpm.org/kuat/cancer/
• Curiel, C. N. (2008, Summer). Skin Cancer Basics.
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  Interview: UMC Vim and Vigor Magazine: Skin Cancer Basics: Summer 2008 edition
• Curiel, C. N. (2007, July). Interview regarding Pigmented lesion clinic.
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  Interview regarding Pigmented lesion clinic. With Pam White of KUAT and a patient, July 31, 2007, Tucson AZ
• Curiel, C. N. (2007, July). Sunblock sun exposure.
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  Media outreach with Steve Stratton, East Valley Tribune
• Curiel, C. N. (2007, June). Arizona #2 in skin cancer.
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  Arizona Daily Star, Interview by Jane Erikson
• Curiel, C. N. (2006, January). Hispanics and melanoma.
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  Interview by Sheryl Kornman for article, Tucson Citizen
• Curiel, C. N. (2006, July). Screen savers.
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  Interview by Jennifer Duffy, Arizona Daily Star
• Curiel, C. N. (2006, June). Skin Cancer Prevention.
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  Media outreach. Skin Cancer Prevention. KGUN 9 News, June 15, 2006, Tucson, AZ.
• Curiel, C. N. (2005, May). Interview for Skin Cancer Awareness.
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  Interview for Skin Cancer Awareness. Channel 7. May, 2005. Tucson, AZ.
• Curiel, C. N. (2003, January). Interview regarding Melanoma awareness.
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  Interview regarding Melanoma awareness. VWBR. 2003, Boston, MA