H-H. Sherry Chow
- Research Scientist, Cancer Center Division
- Research Professor, Medicine
- Research Professor, Pharmaceutical Sciences
- Research Professor, Clinical Translational Sciences
- Member of the Graduate Faculty
Contact
- (520) 626-3358
- Leon Levy Cancer Center, Rm. 4977
- Tucson, AZ 85724
- schow@azcc.arizona.edu
Awards
- Sidney E. Salmon Distinguished Investigator Award
- UACC, Spring 2017
Interests
No activities entered.
Courses
2024-25 Courses
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Dissertation
CTS 920 (Fall 2024)
2023-24 Courses
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Dissertation
CTS 920 (Spring 2024) -
Dissertation
CTS 920 (Fall 2023)
2022-23 Courses
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Dissertation
CTS 920 (Spring 2023) -
Dissertation
CTS 920 (Fall 2022)
2021-22 Courses
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Dissertation
CTS 920 (Spring 2022) -
Dissertation
CTS 920 (Fall 2021)
2020-21 Courses
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Dissertation
CTS 920 (Spring 2021) -
Dissertation
CBIO 920 (Fall 2020) -
Dissertation
CTS 920 (Fall 2020)
2019-20 Courses
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Dissertation
CBIO 920 (Spring 2020) -
Research
CTS 900 (Spring 2020) -
Dissertation
CBIO 920 (Fall 2019) -
Research Conference
CBIO 695A (Fall 2019)
2018-19 Courses
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Dissertation
CBIO 920 (Spring 2019) -
Research
CTS 900 (Spring 2019) -
Research Conference
CBIO 695A (Spring 2019) -
Dissertation
CBIO 920 (Fall 2018) -
Research Conference
CBIO 695A (Fall 2018)
2017-18 Courses
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Directed Rsrch
MCB 492 (Summer I 2018) -
Dissertation
CBIO 920 (Spring 2018) -
Research Conference
CBIO 695A (Spring 2018) -
Dissertation
CBIO 920 (Fall 2017) -
Research Conference
CBIO 695A (Fall 2017)
2016-17 Courses
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Dissertation
CBIO 920 (Spring 2017) -
Research Conference
CBIO 695A (Spring 2017) -
Dissertation
CBIO 920 (Fall 2016) -
Research Conference
CBIO 695A (Fall 2016)
2015-16 Courses
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Dissertation
CBIO 920 (Spring 2016) -
Research
CBIO 900 (Spring 2016) -
Research Conference
CBIO 695A (Spring 2016)
Scholarly Contributions
Journals/Publications
- Desravines, N., Hsu, C. H., Mohnot, S., Sahasrabuddhe, V., House, M., Sauter, E., O'Connor, S., Bauman, J. E., Chow, H. S., & Rahangdale, L. (2023). Feasibility of 5-fluorouracil and imiquimod for the topical treatment of cervical intraepithelial neoplasias (CIN) 2/3. International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics, 163(3), 862-867.More infoTo determine the feasibility (as measured by tolerability and safety) and efficacy of topical 5-fluorouracil (5-FU) and imiquimod for the treatment of cervical intraepithelial neoplasia (CIN) 2/3.
- 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, 143(7), 1299-1302.e3.
- Trejo, M. J., Batai, K., Chen, Y., Brezina, S., Chow, H. S., Ellis, N., Lance, P., Hsu, C. H., Pogreba-Brown, K., Bishop, M., Gsur, A., & Jacobs, E. T. (2023). Genome-Wide Association Study of Metachronous Colorectal Adenoma Risk among Participants in the Selenium Trial. Nutrition and cancer, 75(1), 143-153.More infoGenetic variants related to colorectal adenoma may help identify those who are at highest risk of colorectal cancer development or illuminate potential chemopreventive strategies. The purpose of this genome-wide association study was to identify genetic variants that are associated with risk of developing a metachronous colorectal adenoma among 1,215 study participants of European descent from the Selenium Trial. Associations of variants were assessed with logistic regression analyses and validated in an independent case-control study population of 1,491 participants from the Colorectal Cancer Study of Austria (CORSA). No statistically significant genome-wide associations between any variant and metachronous adenoma were identified after correction for multiple comparisons. However, an intron variant of gene, rs61901554, showed a suggestive association ( = 1.10 × 10) and was associated with advanced adenomas in CORSA ( = 0.04). Two intronic variants, rs12728998 and rs6699944 in were also observed to have suggestive associations with metachronous lesions ( = 2.00 × 10) in the Selenium Trial and were associated with advanced adenoma in CORSA ( = 0.03). Our results provide new areas of investigation for the genetic basis of the development of metachronous colorectal adenoma and support a role for involvement in the Wnt/β-catenin pathway leading to colorectal neoplasia.Trial Registration number: NCT00078897 (ClinicalTrials.gov).
- Vedantham, S., Tseng, H. W., Fu, Z., & Chow, H. S. (2023). Dedicated Cone-Beam Breast CT: Reproducibility of Volumetric Glandular Fraction with Advanced Image Reconstruction Methods. Tomography (Ann Arbor, Mich.), 9(6), 2039-2051.More infoDedicated cone-beam breast computed tomography (CBBCT) is an emerging modality and provides fully three-dimensional (3D) images of the uncompressed breast at an isotropic voxel resolution. In an effort to translate this modality to breast cancer screening, advanced image reconstruction methods are being pursued. Since radiographic breast density is an established risk factor for breast cancer and CBBCT provides volumetric data, this study investigates the reproducibility of the volumetric glandular fraction (VGF), defined as the proportion of fibroglandular tissue volume relative to the total breast volume excluding the skin. Four image reconstruction methods were investigated: the analytical Feldkamp-Davis-Kress (FDK), a compressed sensing-based fast, regularized, iterative statistical technique (FRIST), a fully supervised deep learning approach using a multi-scale residual dense network (MS-RDN), and a self-supervised approach based on Noise-to-Noise (N2N) learning. Projection datasets from 106 women who participated in a prior clinical trial were reconstructed using each of these algorithms at a fixed isotropic voxel size of (0.273 mm). Each reconstructed breast volume was segmented into skin, adipose, and fibroglandular tissues, and the VGF was computed. The VGF did not differ among the four reconstruction methods ( = 0.167), and none of the three advanced image reconstruction algorithms differed from the standard FDK reconstruction ( > 0.862). Advanced reconstruction algorithms developed for low-dose CBBCT reproduce the VGF to provide quantitative breast density, which can be used for risk estimation.
- Zeng, Y., Moscicki, A. B., Woo, H., Hsu, C. H., Kemp, T. J., Pinto, L. A., Szabo, E., Dimond, E., Bauman, J., Sahasrabuddhe, V. V., & Chow, H. S. (2023). HPV16/18 Antibody Responses After a Single Dose of Nonavalent HPV Vaccine. Pediatrics, 152(1).More infoA single dose of human papillomavirus (HPV) vaccine would simplify logistics and reduce costs of vaccination programs worldwide. We conducted a phase IIa trial to determine the stability of HPV type-specific antibody responses after a single dose of the nonavalent HPV vaccine, Gardasil9.
- Bauman, J. E., Hsu, C. H., Centuori, S., Guillen-Rodriguez, J., Garland, L. L., Ho, E., Padi, M., Bageerathan, V., Bengtson, L., Wojtowicz, M., Szabo, E., & Chow, H. S. (2022). Randomized Crossover Trial Evaluating Detoxification of Tobacco Carcinogens by Broccoli Seed and Sprout Extract in Current Smokers. Cancers, 14(9).More infoConsumption of cruciferous vegetables, rich in the isothiocyanate glucoraphanin, is associated with reduced risk of tobacco-related cancers. Sulforaphane, released by hydrolysis of glucoraphanin, potently induces cytoprotective phase II enzymes. Sulforaphane decreased the incidence of oral cancer in the 4NQO carcinogenesis model. In residents of Qidong, China, broccoli seed and sprout extracts (BSSE) increased detoxification of air pollutants benzene and acrolein, also found in tobacco smoke. This randomized, crossover trial evaluated detoxification of tobacco carcinogens by the BSSE Avmacol in otherwise healthy smokers. Participants were treated for 2 weeks with both low and higher-dose BSSE (148 µmol vs. 296 µmol of glucoraphanin daily), separated by a 2-week washout, with randomization to low-high vs. high-low sequence. The primary endpoint was detoxification of benzene, measured by urinary excretion of its mercapturic acid, SPMA. Secondary endpoints included bioavailability, detoxification of acrolein and crotonaldehyde, modulation by genotype, and toxicity. Forty-nine participants enrolled, including 26 (53%) females with median use of 20 cigarettes/day. Low and higher-dose BSSE showed a mean bioavailability of 11% and 10%, respectively. Higher-dose BSSE significantly upregulated urinary excretion of the mercapturic acids of benzene ( = 0.04), acrolein ( < 0.01), and crotonaldehyde ( = 0.02), independent of genotype. Retention and compliance were high resulting in early study completion. In conclusion, BSSE significantly upregulated detoxification of the tobacco carcinogens benzene, acrolein, and crotonaldehyde in current tobacco smokers.
- Garland, L. L., Guillen-Rodriguez, J., Hsu, C. H., Davis, L. E., Szabo, E., Husted, C. R., Liu, H., LeClerc, A., Alekseyev, Y. O., Liu, G., Bauman, J. E., Spira, A. E., Beane, J., Wojtowicz, M., & Chow, H. S. (2022). Clinical Study of Aspirin and Zileuton on Biomarkers of Tobacco-Related Carcinogenesis in Current Smokers. Cancers, 14(12).More infoThe chemopreventive effect of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) on lung cancer risk is supported by epidemiologic and preclinical studies. Zileuton, a 5-lipoxygenase inhibitor, has additive activity with NSAIDs against tobacco carcinogenesis in preclinical models. We hypothesized that cyclooxygenase plus 5-lipoxygenase inhibition would be more effective than a placebo in modulating the nasal epithelium gene signatures of tobacco exposure and lung cancer. We conducted a randomized, double-blinded study of low-dose aspirin plus zileuton vs. double placebo in current smokers to compare the modulating effects on nasal gene expression and arachidonic acid metabolism. In total, 63 participants took aspirin 81 mg daily plus zileuton (Zyflo CR) 600 mg BID or the placebo for 12 weeks. Nasal brushes from the baseline, end-of-intervention, and one-week post intervention were profiled via microarray. Aspirin plus zilueton had minimal effects on the modulation of the nasal or bronchial gene expression signatures of smoking, lung cancer, and COPD but favorably modulated a bronchial gene expression signature of squamous dysplasia. Aspirin plus zileuton suppressed urinary leukotriene but not prostaglandin E2, suggesting shunting through the cyclooxygenase pathway when combined with 5-lipoxygenase inhibition. Continued investigation of leukotriene inhibitors is needed to confirm these findings, understand the long-term effects on the airway epithelium, and identify the safest, optimally dosed agents.
- Jacobs, E. T., Martinez, J., Batai, K., Lance, P., Trejo, M., Saboda, K., Cordova, C., Chew, W., Habila, M., & Chow, H. S. (2022). Effect Modification of Selenium Supplementation by Intake and Serum Concentrations of Antioxidants on the Development of Metachronous Colorectal Adenoma. Nutrition and cancer, 1-10.More infoSelenium (Se) is a trace element that has been investigated as a potential chemopreventive agent for colorectal cancer. Dietary intake of other antioxidant nutrients may modify the effect of Se.
- Martinez, J. A., Wertheim, B. C., Roe, D. J., Chalasani, P., Cohen, J., Baer, L., Chow, H. S., Stopeck, A. T., & Thompson, P. A. (2022). Sulindac Improves Stiffness and Quality of Life in Women Taking Aromatase Inhibitors for Breast Cancer. Breast cancer research and treatment, 192(1), 113-122.More infoTo examine benefit of sulindac for relief of musculoskeletal symptoms (MSS) in patients stable on aromatase inhibitors (AIs).
- Parsons, J. K., Pinto, P. A., Pavlovich, C. P., Uchio, E., Nguyen, M. N., Kim, H. L., Gulley, J. L., Sater, H. A., Jamieson, C., Hsu, C. H., Wojtowicz, M., House, M., Schlom, J., Donahue, R. N., Dahut, W. L., Madan, R. A., Bailey, S., Centuori, S., Bauman, J. E., , Parnes, H. L., et al. (2022). A Phase 2, Double-blind, Randomized Controlled Trial of PROSTVAC in Prostate Cancer Patients on Active Surveillance. European urology focus.More infoThere is an unmet clinical need for interventions to prevent disease progression in patients with localized prostate cancer on active surveillance (AS).
- 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).More infoNonmelanoma 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.
- Ying, J., Cattell, R., Zhao, T., Lei, L., Jiang, Z., Hussain, S. M., Gao, Y., Chow, H. S., Stopeck, A. T., Thompson, P. A., & Huang, C. (2022). Two fully automated data-driven 3D whole-breast segmentation strategies in MRI for MR-based breast density using image registration and U-Net with a focus on reproducibility. Visual computing for industry, biomedicine, and art, 5(1), 25.More infoPresence of higher breast density (BD) and persistence over time are risk factors for breast cancer. A quantitatively accurate and highly reproducible BD measure that relies on precise and reproducible whole-breast segmentation is desirable. In this study, we aimed to develop a highly reproducible and accurate whole-breast segmentation algorithm for the generation of reproducible BD measures. Three datasets of volunteers from two clinical trials were included. Breast MR images were acquired on 3 T Siemens Biograph mMR, Prisma, and Skyra using 3D Cartesian six-echo GRE sequences with a fat-water separation technique. Two whole-breast segmentation strategies, utilizing image registration and 3D U-Net, were developed. Manual segmentation was performed. A task-based analysis was performed: a previously developed MR-based BD measure, MagDensity, was calculated and assessed using automated and manual segmentation. The mean squared error (MSE) and intraclass correlation coefficient (ICC) between MagDensity were evaluated using the manual segmentation as a reference. The test-retest reproducibility of MagDensity derived from different breast segmentation methods was assessed using the difference between the test and retest measures (Δ), MSE, and ICC. The results showed that MagDensity derived by the registration and deep learning segmentation methods exhibited high concordance with manual segmentation, with ICCs of 0.986 (95%CI: 0.974-0.993) and 0.983 (95%CI: 0.961-0.992), respectively. For test-retest analysis, MagDensity derived using the registration algorithm achieved the smallest MSE of 0.370 and highest ICC of 0.993 (95%CI: 0.982-0.997) when compared to other segmentation methods. In conclusion, the proposed registration and deep learning whole-breast segmentation methods are accurate and reliable for estimating BD. Both methods outperformed a previously developed algorithm and manual segmentation in the test-retest assessment, with the registration exhibiting superior performance for highly reproducible BD measurements.
- Algotar, A. M., Hsu, C. H., Chow, H. H., Dougherty, S. T., Babiker, H. M., Marrero, D. G., Abraham, I., Kumar, R., Ligibel, J. A., Courneya, K. S., Smith, T. E., Jones, P. A., Lopez, J. N., Niemiro, G., Ramakumar, S., Hoy, R. D., Mack, C., & Thomson, C. A. (2021). Comprehensive Lifestyle Improvement Program for Prostate Cancer (CLIPP) is associated with improvement in weight and components of metabolic syndrome in men exposed to androgen deprivation therapy for prostate cancer. Prostate cancer and prostatic diseases, 24(3), 903-909.More infoAndrogen deprivation therapy (ADT) for prostate cancer is associated with adverse effects, such as obesity and metabolic syndrome, which increase cardiovascular risk, the most common cause of non-cancer mortality in men diagnosed with prostate cancer. The Comprehensive Lifestyle Improvement Program for Prostate Cancer (CLIPP) was created to determine the feasibility of conducing a comprehensive lifestyle modification intervention in men on ADT for prostate cancer and determine its early efficacy in reducing obesity and metabolic syndrome.
- Algotar, A. M., Kumar, R., Babiker, H. M., Dougherty, S. T., Hsu, C. H., Chow, H. H., Smith, T. E., Marrero, D. G., Courneya, K. S., Abraham, I., Ligibel, J. A., & Thomson, C. A. (2021). Protocol for a feasibility and early efficacy study of the Comprehensive Lifestyle Improvement Program for Prostate Cancer-2 (CLIPP2). Contemporary clinical trials communications, 21, 100701.More infoAlthough androgen deprivation therapy (ADT) for prostate cancer demonstrates improved overall and disease-free survival, it is associated with adverse effects such as obesity and metabolic syndrome that increase risk of cardiometabolic disease and diabetes type 2. ADT also leads to fatigue, depression and erectile dysfunction, which reduce quality of life (QoL). Lifestyle modification has shown promise in reducing obesity, metabolic syndrome and diabetes type 2 in other disease types. However, there is a paucity of data regarding the utility of lifestyle modification in men receiving ADT for prostate cancer.
- 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).More infoThere 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.
- Gutkind, J. S., Molinolo, A. A., Wu, X., Wang, Z., Nachmanson, D., Harismendy, O., Alexandrov, L. B., Wuertz, B. R., Ondrey, F. G., Laronde, D., Rock, L. D., Rosin, M., Coffey, C., Butler, V. D., Bengtson, L., Hsu, C. H., Bauman, J. E., Hewitt, S. M., Cohen, E. E., , Chow, H. S., et al. (2021). Inhibition of mTOR signaling and clinical activity of metformin in oral premalignant lesions. JCI insight, 6(17).More infoBACKGROUNDThe aberrant activation of the PI3K/mTOR signaling circuitry is one of the most frequently dysregulated signaling events in head and neck squamous cell carcinoma (HNSCC). Here, we conducted a single-arm, open-label phase IIa clinical trial in individuals with oral premalignant lesions (OPLs) to explore the potential of metformin to target PI3K/mTOR signaling for HNSCC prevention.METHODSIndividuals with OPLs, but who were otherwise healthy and without diabetes, underwent pretreatment and posttreatment clinical exam and biopsy. Participants received metformin for 12 weeks (week 1, 500 mg; week 2, 1000 mg; weeks 3-12, 2000 mg daily). Pretreatment and posttreatment biopsies, saliva, and blood were obtained for biomarker analysis, including IHC assessment of mTOR signaling and exome sequencing.RESULTSTwenty-three participants were evaluable for response. The clinical response rate (defined as a ≥50% reduction in lesion size) was 17%. Although lower than the proposed threshold for favorable clinical response, the histological response rate (improvement in histological grade) was 60%, including 17% complete responses and 43% partial responses. Logistic regression analysis revealed that when compared with never smokers, current and former smokers had statistically significantly increased histological responses (P = 0.016). Remarkably, a significant correlation existed between decreased mTOR activity (pS6 IHC staining) in the basal epithelial layers of OPLs and the histological (P = 0.04) and clinical (P = 0.01) responses.CONCLUSIONTo our knowledge this is the first phase II trial of metformin in individuals with OPLs, providing evidence that metformin administration results in encouraging histological responses and mTOR pathway modulation, thus supporting its further investigation as a chemopreventive agent.TRIAL REGISTRATIONNCT02581137FUNDINGNIH contract HHSN261201200031I, grants R01DE026644 and R01DE026870.
- Martinez, J. A., Skiba, M. B., Chow, H. S., Chew, W. M., Saboda, K., Lance, P., Ellis, N. A., & Jacobs, E. T. (2021). A Protective Role for Arachidonic Acid Metabolites against Advanced Colorectal Adenoma in a Phase III Trial of Selenium. Nutrients, 13(11).More infoOxylipins derived from arachidonic acid (ARA) have been implicated in the development of colorectal adenomas and colorectal cancer. The primary purpose of this work was to determine the relationship between plasma levels of oxylipins and colorectal adenoma characteristics at study entry, as well as with the development of a new adenoma during follow-up within a Phase III adenoma prevention clinical trial with selenium (Sel). Secondarily, we sought to determine whether the selenium intervention influenced plasma oxylipin levels. Four oxylipins were quantified in stored plasma samples from a subset of Sel study subjects ( = 256) at baseline and at 12-months. There were significantly lower odds of an advanced adenoma at baseline with higher prostaglandin E (PGE), with an OR (95% CI) of 0.55 (0.33-0.92), and with 5-hydroxyeicosatetraenoic acid (5-HETE) ((0.53 (0.33-0.94)); and of a large adenoma with higher PGE ((0.52 (0.31-0.87)). In contrast, no associations were observed between any oxylipin and the development of a new adenoma during follow-up. Selenium supplementation was associated with a significantly smaller increase in 5-HETE after 12 months compared to the placebo, though no other results were statistically significant. The ARA-derived oxylipins may have a role in the progression of non-advanced adenoma to advanced, but not with the development of a new adenoma.
- Selmin, O. I., Papoutsis, A. J., Hazan, S., Smith, C., Greenfield, N., Donovan, M. G., Wren, S. N., Doetschman, T. C., Snider, J. M., Snider, A. J., Chow, S. H., & Romagnolo, D. F. (2021). -6 High Fat Diet Induces Gut Microbiome Dysbiosis and Colonic Inflammation. International journal of molecular sciences, 22(13).More info: Concerns are emerging that a high-fat diet rich in -6 PUFA (-6HFD) may alter gut microbiome and increase the risk of intestinal disorders. Research is needed to model the relationships between consumption of an -6HFD starting at weaning and development of gut dysbiosis and colonic inflammation in adulthood. We used a C57BL/6J mouse model to compare the effects of exposure to a typical American Western diet (WD) providing 58.4%, 27.8%, and 13.7% energy (%E) from carbohydrates, fat, and protein, respectively, with those of an isocaloric and isoproteic soybean oil-rich -6HFD providing 50%E and 35.9%E from total fat and carbohydrates, respectively on gut inflammation and microbiome profile. : At weaning, male offspring were assigned to either the WD or -6HFD through 10-16 weeks of age. The WD included fat exclusively from palm oil whereas the -6HFD contained fat exclusively from soybean oil. We recorded changes in body weight, cyclooxygenase-2 (COX-2) expression, colon histopathology, and gut microbiome profile. : Compared to the WD, the -6HFD increased plasma levels of -6 fatty acids; colonic expression of COX-2; and the number of colonic inflammatory and hyperplastic lesions. At 16 weeks of age, the -6HFD caused a marked reduction in the gut presence of , , and , and induced growth of and . At the species level, the -6HFD sustains the gut growth of proinflammatory and . : An -6HFD consumed from weaning to adulthood induces a shift in gut bacterial profile associated with colonic inflammation.
- Tapia, E., Villa-Guillen, D. E., Chalasani, P., Centuori, S., Roe, D. J., Guillen-Rodriguez, J., Huang, C., Galons, J. P., Thomson, C. A., Altbach, M., Trujillo, J., Pinto, L., Martinez, J. A., Algotar, A. M., & Chow, H. S. (2021). A randomized controlled trial of metformin in women with components of metabolic syndrome: intervention feasibility and effects on adiposity and breast density. Breast cancer research and treatment, 190(1), 69-78.More infoObesity is a known risk factor for post-menopausal breast cancer and may increase risk for triple negative breast cancer in premenopausal women. Intervention strategies are clearly needed to reduce obesity-associated breast cancer risk.
- Thompson, P. A., Huang, C., Yang, J., Wertheim, B. C., Roe, D., Zhang, X., Ding, J., Chalasani, P., Preece, C., Martinez, J., Chow, H. S., & Stopeck, A. T. (2021). Sulindac, a Nonselective NSAID, Reduces Breast Density in Postmenopausal Women with Breast Cancer Treated with Aromatase Inhibitors. Clinical cancer research : an official journal of the American Association for Cancer Research, 27(20), 5660-5668.More infoTo evaluate the effect of sulindac, a nonselective anti-inflammatory drug (NSAID), for activity to reduce breast density (BD), a risk factor for breast cancer.
- Batai, K., Trejo, M. J., Chen, Y., Kohler, L. N., Lance, P., Ellis, N. A., Cornelis, M. C., Chow, H. S., Hsu, C. H., & Jacobs, E. T. (2020). Genome-Wide Association Study of Response to Selenium Supplementation and Circulating Selenium Concentrations in Adults of European Descent. The Journal of nutrition.More infoSelenium (Se) is a trace element that has been linked to many health conditions. Genome-wide association studies (GWAS) have identified variants for blood and toenail Se levels, but no GWAS has been conducted to date on responses to Se supplementation.
- Kunihiro, A. G., Luis, P. B., Frye, J. B., Chew, W., Chow, H. H., Schneider, C., & Funk, J. L. (2020). Bone-Specific Metabolism of Dietary Polyphenols in Resorptive Bone Diseases. Molecular nutrition & food research, 64(14), e2000072.More infoCurcumin prevents bone loss in resorptive bone diseases and inhibits osteoclast formation, a key process driving bone loss. Curcumin circulates as an inactive glucuronide that can be deconjugated in situ by bone's high β-glucuronidase (GUSB) content, forming the active aglycone. Because curcumin is a common remedy for musculoskeletal disease, effects of microenvironmental changes consequent to skeletal development or disease on bone curcumin metabolism are explored.
- Garland, L. L., Guillen-Rodriguez, J., Hsu, C. H., Yozwiak, M., Zhang, H. H., Alberts, D. S., Davis, L. E., Szabo, E., Merenstein, C., Lel, J., Zhang, X., Liu, H., Liu, G., Spira, A. E., Beane, J. E., Wojtowicz, M., & Chow, H. S. (2019). Effect of Intermittent Versus Continuous Low-Dose Aspirin on Nasal Epithelium Gene Expression in Current Smokers: A Randomized, Double-Blinded Trial. Cancer prevention research (Philadelphia, Pa.), 12(11), 809-820.More infoA chemopreventive effect of aspirin (ASA) on lung cancer risk is supported by epidemiologic and preclinical studies. We conducted a randomized, double-blinded study in current heavy smokers to compare modulating effects of intermittent versus continuous low-dose ASA on nasal epithelium gene expression and arachidonic acid (ARA) metabolism. Fifty-four participants were randomized to intermittent (ASA 81 mg daily for one week/placebo for one week) or continuous (ASA 81 mg daily) for 12 weeks. Low-dose ASA suppressed urinary prostaglandin E2 metabolite (PGEM; change of -4.55 ± 11.52 from baseline 15.44 ± 13.79 ng/mg creatinine for arms combined, = 0.02), a surrogate of COX-mediated ARA metabolism, but had minimal effects on nasal gene expression of nasal or bronchial gene-expression signatures associated with smoking, lung cancer, and chronic obstructive pulmonary disease. Suppression of urinary PGEM correlated with favorable changes in a smoking-associated gene signature ( < 0.01). Gene set enrichment analysis (GSEA) showed that ASA intervention led to 1,079 enriched gene sets from the Canonical Pathways within the Molecular Signatures Database. In conclusion, low-dose ASA had minimal effects on known carcinogenesis gene signatures in nasal epithelium of current smokers but results in wide-ranging genomic changes in the nasal epithelium, demonstrating utility of nasal brushings as a surrogate to measure gene-expression responses to chemoprevention. PGEM may serve as a marker for smoking-associated gene-expression changes and systemic inflammation. Future studies should focus on NSAIDs or agent combinations with broader inhibition of pro-inflammatory ARA metabolism to shift gene signatures in an anti-carcinogenic direction.
- Jacobs, E. T., Lance, P., Mandarino, L. J., Ellis, N. A., Chow, H. S., Foote, J., Martinez, J. A., Hsu, C. P., Batai, K., Saboda, K., & Thompson, P. A. (2019). Selenium supplementation and insulin resistance in a randomized, clinical trial. BMJ open diabetes research & care, 7(1), e000613.More infoWhile controversial, observational and randomized clinical trial data implicate the micronutrient selenium (Se) in the development of type 2 diabetes (T2D). The aim of this study was to test the hypothesis that Se supplementation adversely affects pancreatic β-cell function and insulin sensitivity.
- Kunihiro, A. G., Luis, P. B., Brickey, J. A., Frye, J. B., Chow, H. S., Schneider, C., & Funk, J. L. (2019). Beta-Glucuronidase Catalyzes Deconjugation and Activation of Curcumin-Glucuronide in Bone. Journal of natural products, 82(3), 500-509.More infoThe biological basis for documented in vivo bone-protective effects of turmeric-derived curcumin is unclear since curcumin is barely detectable in serum, being rapidly conjugated to form what is thought to be an inactive glucuronide. Studies were therefore undertaken to test the postulate that antiresorptive effects of curcumin require deconjugation within bone to form the bioactive aglycone and that β-glucuronidase (GUSB), a deconjugating enzyme expressed by hematopoietic marrow cells, facilitates this site-specific transformation. Consistent with this postulate, aglycone, but not glucuronidated, curcumin inhibited RANKL-stimulated osteoclastogenesis, a key curcumin target in bone. Aglycone curcumin, expressed relative to total curcumin, was higher in bone marrow than in serum of curcumin-treated C57BL/6J mice, while remaining a minor component. Ex vivo, under conditions preventing further metabolism of the unstable aglycone, the majority of curcumin-glucuronide delivered to marrow in vivo was hydrolyzed to the aglycone, a process that was inhibited by treatment with saccharolactone, a GUSB inhibitor, or in mice having reduced (C3H/HeJ) or absent (mps/mps) GUSB activity. These findings suggest that curcumin, despite low systemic bioavailability, may be enzymatically activated (deconjugated) within GUSB-enriched bone to exert protective effects, a metabolic process that could also contribute to bone-protective effects of other highly glucuronidated dietary polyphenols.
- Song, J. H., Kang, H. J., Luevano, L. A., Gokhale, V., Wu, K., Pandey, R., Sherry Chow, H. H., Hurley, L. H., & Kraft, A. S. (2019). Small-Molecule-Targeting Hairpin Loop of hTERT Promoter G-Quadruplex Induces Cancer Cell Death. Cell chemical biology, 26(8), 1110-1121.e4.More infoIncreased telomerase activity is associated with malignancy and poor prognosis in human cancer, but the development of targeted agents has not yet provided clinical benefit. Here we report that, instead of targeting the telomerase enzyme directly, small molecules that bind to the G-hairpin of the hTERT G-quadruplex-forming sequence kill selectively malignant cells without altering the function of normal cells. RG260 targets the hTERT G-quadruplex stem-loop folding but not tetrad DNAs, leading to downregulation of hTERT expression. To improve physicochemical and pharmacokinetic properties, we derived a small-molecule analog, RG1603, from the parent compound. RG1603 induces mitochondrial defects including PGC1α and NRF2 inhibition and increases oxidative stress, followed by DNA damage and apoptosis. RG1603 injected as a single agent has tolerable toxicity while achieving strong anticancer efficacy in a tumor xenograft mouse model. These results demonstrate a unique approach to inhibiting the hTERT that functions by impairing mitochondrial activity, inducing cell death.
- Zeng, Y., Moscicki, A. B., Sahasrabuddhe, V. V., Garcia, F., Woo, H., Hsu, C. H., Szabo, E., Dimond, E., Vanzzini, S., Mondragon, A., Butler, V., DeRose, H., & Chow, H. S. (2019). A prospective, single-arm, open-label, non-randomized, phase IIa trial of a nonavalent prophylactic HPV vaccine to assess immunogenicity of a prime and deferred-booster dosing schedule among 9-11 year-old girls and boys - clinical protocol. BMC cancer, 19(1), 290.More infoHuman papillomavirus (HPV) vaccines are indicated for the prevention of cancers and genital warts caused by vaccine-covered HPV types. Although the standard regimen requires a two or three-dose vaccine series, there is emerging data suggesting that a single dose of the bivalent or quadrivalent HPV vaccine generates persistently positive antibody titers. No similar data is yet available for the nonavalent HPV vaccine, currently the only HPV vaccine available in the United States. The overall objective of our study is to assess the stability and kinetics of antibody titers for 24 months following a single dose of the nonavalent HPV vaccine among preteen girls and boys.
- Chow, H. (2018). Effects of Black and Green Tea Consumption on Blood Pressure and Liver Enzymes: A Randomized Controlled Trial. J Nutr Food Sci, 8, 661. doi:10.4172/2155-9600.1000661
- Kohler, L. N., Florea, A., Kelley, C. P., Chow, S., Hsu, P., Batai, K., Saboda, K., Lance, P., & Jacobs, E. T. (2018). Higher Plasma Selenium Concentrations Are Associated with Increased Odds of Prevalent Type 2 Diabetes. The Journal of nutrition, 148(8), 1333-1340.More infoSelenium, an essential trace element, has been investigated as a potential cancer prevention agent. However, several studies have indicated that selenium supplementation may be associated with an increased risk of type 2 diabetes (T2D), although an equivocal relation of this nature requires confirmation.
- Kohler, L. N., Foote, J., Kelley, C. P., Florea, A., Shelly, C., Chow, H. S., Hsu, P., Batai, K., Ellis, N., Saboda, K., Lance, P., & Jacobs, E. T. (2018). Selenium and Type 2 Diabetes: Systematic Review. Nutrients, 10(12).More infoSeveral studies have investigated the potential role of selenium (Se) in the development of type 2 diabetes (T2D) with disparate findings. We conducted a systematic review and meta-analysis to synthesize the evidence of any association between Se and T2D. PubMed, Embase, and Scopus were searched following the Preferred Reporting Items for Systematic Reviews and Meta-analysis Approach (PRISMA). Sixteen studies from 15 papers met inclusion criteria defined for this review. Of the 13 observational studies included, 8 demonstrated a statistically significant positive association between concentrations of Se and odds for T2D, with odds ratios (95% confidence intervals) ranging from 1.52 (1.01⁻2.28) to 7.64 (3.34⁻17.46), and a summary odds ratio (OR) (95% confidence interval (CI)) of 2.03 (1.51⁻2.72). In contrast, among randomized clinical trials (RCTs) of Se, a higher risk of T2D was not observed for those who received Se compared to a placebo (OR = 1.18, 95% CI 0.95⁻1.47). Taken together, the results for the relationship between Se and T2D differ between observational studies and randomized clinical trials (RCTs). It remains unclear whether these differences are the result of uncontrolled confounding in the observational studies, or whether there is a modest effect of Se on the risk for T2D that may vary by duration of exposure. Further investigations on the effects of Se on glucose metabolism are needed.
- Nguyen, M. M., Martinez, J. A., Hsu, C. H., Sokoloff, M., Krouse, R. S., Gibson, B. A., Nagle, R. B., Parnes, H. L., Cordova, C., & Chow, H. S. (2018). Bioactivity and prostate tissue distribution of metformin in a preprostatectomy prostate cancer cohort. European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP), 27(6), 557-562.More infoMetformin has recently been shown to have potential to reduce prostate cancer risk. We conducted a randomized, double-blind, placebo-controlled trial to determine the modulating effects of metformin on tissue and systemic biomarkers of drug activity and its distribution into the prostate tissue. Twenty patients with prostate cancer scheduled to undergo prostatectomy were randomly assigned to receive either extended-release metformin or placebo for a median of 34 days before surgery. Prostatectomy and serum samples were analyzed for metformin concentrations, serum biomarkers of drug activity (prostate-specific antigen, insulin, insulin-like growth factor-1, insulin-like growth factor binding protein 3, sex hormone-binding globulin, and testosterone) and tissue biomarkers of proliferation, apoptosis, cell cycle regulation, and mTOR inhibition. For participants in the metformin arm, the prostate tissue and serum metformin concentrations ranged from 0.88 to 51.2 μg/g tissue and from not detectable to 3.6 μg/ml, respectively. There were no differences between the two groups in either the postintervention tissue biomarker expression in the prostatectomy tissue or pre to postintervention changes in serum biomarkers. We conclude that metformin distributes to human prostate tissue, suggesting that metformin could exert its effects directly on tissue targets. However, there was no difference in tissue and systemic drug effect biomarkers between the two treatment arms. Future studies with longer intervention duration and larger sample size should be considered in order to evaluate the potential of metformin for prostate cancer prevention.
- Parsons, J. K., Pinto, P. A., Pavlovich, C. P., Uchio, E., Kim, H. L., Nguyen, M. N., Gulley, J. L., Jamieson, C., Hsu, P., Wojtowicz, M., Parnes, H., Schlom, J., Dahut, W. L., Madan, R. A., Donahue, R. N., & Chow, H. S. (2018). A Randomized, Double-blind, Phase II Trial of PSA-TRICOM (PROSTVAC) in Patients with Localized Prostate Cancer: The Immunotherapy to Prevent Progression on Active Surveillance Study. European urology focus, 4(5), 636-638.More infoThe Immunotherapy to Prevent Progression on Active Surveillance Study is the first trial of immunotherapy for localized prostate cancer. We randomized active surveillance patients to PSA-TRICOM (PROSTVAC) or placebo for 5mo. Final results will be available in 2019.
- Chow, H. (2017). Modulation of oxidative damage by green and black tea: role of smoking and gender in a randomized trial. J Nutr Food Sci, 7, 633. doi:10.4172/2155-9600.1000633
- Gattoc, L., Frew, P. M., Thomas, S. N., Easley, K. A., Ward, L., Chow, H. S., Ura, C. A., & Flowers, L. (2017). Phase I dose-escalation trial of intravaginal curcumin in women for cervical dysplasia. Open access journal of clinical trials, 9, 1-10.More infoThis is a Phase I trial demonstrating safety and tolerability of intravaginal curcumin for future use in women with cervical neoplasia.
- Guthrie, A. R., Chow, H. S., & Martinez, J. A. (2017). Effects of resveratrol on drug- and carcinogen-metabolizing enzymes, implications for cancer prevention. Pharmacology research & perspectives, 5(1), e00294.More infoResveratrol is a polyphenol found in grape skins and peanuts that has demonstrated many health benefits including protection against aging, cardiovascular and metabolic disease, neurological decline, and cancer. The anticancer properties of resveratrol have been attributed to a variety of mechanisms, including its general inhibition of phase I metabolism and induction of phase II metabolism. The effects of resveratrol on these enzymes, however, are still unclear, as in vitro evidence often contrasts with animal studies and clinical trials. Reasons for these variances could include the low bioavailability of resveratrol and the effects of resveratrol metabolites. Due to resveratrol's interactions with drug-metabolizing enzymes and drug transporters, individuals concurrently taking pharmacological doses of resveratrol with other supplements or medications could potentially experience nutrient-drug interactions. This review summarizes the known effects of resveratrol and its main metabolites on drug metabolism in order to help characterize which populations might benefit from resveratrol for the prevention of cancer, as well as those that may need to avoid supplementation due to potential drug interactions.
- Thomson, C. A., Chow, H. H., Wertheim, B. C., Roe, D. J., Stopeck, A., Maskarinec, G., Altbach, M., Chalasani, P., Huang, C., Strom, M. B., Galons, J. P., & Thompson, P. A. (2017). A randomized, placebo-controlled trial of diindolylmethane for breast cancer biomarker modulation in patients taking tamoxifen. Breast cancer research and treatment, 165(1), 97-107.More infoDiindolylmethane (DIM), a bioactive metabolite of indole-3-carbinol found in cruciferous vegetables, has proposed cancer chemoprevention activity in the breast. There is limited evidence of clinically relevant activity of DIM or long-term safety data of its regular use. A randomized, double-blind, placebo-controlled trial was conducted to determine the activity and safety of combined use of BioResponse DIM® (BR-DIM) with tamoxifen.
- Banerjee, B., Shaheen, N. J., Martinez, J. A., Hsu, C., Trowers, E., Gibson, B. A., Della'Zanna, G., Richmond, E., & Chow, H. S. (2016). Clinical Study of Ursodeoxycholic Acid in Barrett's Esophagus Patients. Cancer prevention research (Philadelphia, Pa.), 9(7), 528-33.More infoPrior research strongly implicates gastric acid and bile acids, two major components of the gastroesophageal refluxate, in the development of Barrett's esophagus and its pathogenesis. Ursodeoxycholic acid (UDCA), a hydrophilic bile acid, has been shown to protect esophageal cells against oxidative stress induced by cytotoxic bile acids. We conducted a pilot clinical study to evaluate the clinical activity of UDCA in patients with Barrett's esophagus. Twenty-nine patients with Barrett's esophagus received UDCA treatment at a daily dose of 13 to 15 mg/kg/day for 6 months. The clinical activity of UDCA was assessed by evaluating changes in gastric bile acid composition and markers of oxidative DNA damage (8-hydroxydeoxyguanosine), cell proliferation (Ki67), and apoptosis (cleaved caspase-3) in Barrett's esophagus epithelium. The bile acid concentrations in gastric fluid were measured by liquid chromatography/mass spectrometry. At baseline, UDCA (sum of unchanged and glycine/taurine conjugates) accounted for 18.2% of total gastric bile acids. After UDCA intervention, UDCA increased significantly to account for 93.4% of total gastric bile acids (P < 0.0001). The expression of markers of oxidative DNA damage, cell proliferation, and apoptosis was assessed in the Barrett's esophagus biopsies by IHC. The selected tissue biomarkers were unchanged after 6 months of UDCA intervention. We conclude that high-dose UDCA supplementation for 6 months resulted in favorable changes in gastric bile acid composition but did not modulate selected markers of oxidative DNA damage, cell proliferation, and apoptosis in the Barrett's esophagus epithelium. Cancer Prev Res; 9(7); 528-33. ©2016 AACRSee related article by Brian J. Reid, p. 512.
- López, A. M., Pruthi, S., Boughey, J. C., Perloff, M., Hsu, C., Lang, J. E., Ley, M., Frank, D., Taverna, J. A., & Chow, H. S. (2016). Double-Blind, Randomized Trial of Alternative Letrozole Dosing Regimens in Postmenopausal Women with Increased Breast Cancer Risk. Cancer prevention research (Philadelphia, Pa.), 9(2), 142-8.More infoAromatase inhibitors (AI) profoundly suppress estrogen levels in postmenopausal women and are effective in breast cancer prevention among high-risk postmenopausal women. Unfortunately, AI treatment is associated with undesirable side effects that limit patient acceptance for primary prevention of breast cancer. A double-blind, randomized trial was conducted to determine whether low and intermittent doses of letrozole can achieve effective estrogen suppression with a more favorable side-effect profile. Overall, 112 postmenopausal women at increased risk for breast cancer were randomized to receive letrozole at 2.5 mg once daily (QD, standard dose arm), 2.5 mg every Monday, Wednesday, and Friday (Q-MWF), 1.0 mg Q-MWF, or 0.25 mg Q-MWF for 24 weeks. Primary endpoint was suppression in serum estradiol levels at the end of letrozole intervention. Secondary endpoints included changes in serum estrone, testosterone, C-telopeptide (marker of bone resorption), lipid profile, and quality-of-life measures (QoL) following treatment. Significant estrogen suppression was observed in all dose arms with an average of 75% to 78% and 86% to 93% reduction in serum estradiol and estrone levels, respectively. There were no differences among dose arms with respect to changes in C-telopeptide levels, lipid profile, adverse events (AE), or QoL measures. We conclude that low and intermittent doses of letrozole are not inferior to standard dose in estrogen suppression and resulted in a similar side-effect profile compared with standard dose. Further studies are needed to determine the feasibility of selecting an effective AI dosing schedule with better tolerability. Cancer Prev Res; 9(2); 142-8. ©2015 AACR.
- Martinez, J. A., Chalasani, P., Thomson, C. A., Roe, D., Altbach, M., Galons, J., Stopeck, A., Thompson, P. A., Villa-Guillen, D. E., & Chow, H. S. (2016). Phase II study of metformin for reduction of obesity-associated breast cancer risk: a randomized controlled trial protocol. BMC cancer, 16, 500.More infoTwo-thirds of U.S. adult women are overweight or obese. High body mass index (BMI) and adult weight gain are risk factors for a number of chronic diseases, including postmenopausal breast cancer. The higher postmenopausal breast cancer risk in women with elevated BMI is likely to be attributable to related metabolic disturbances including altered circulating sex steroid hormones and adipokines, elevated pro-inflammatory cytokines, and insulin resistance. Metformin is a widely used antidiabetic drug that has demonstrated favorable effects on metabolic disturbances and as such may lead to lower breast cancer risk in obese women. Further, the anti-proliferative effects of metformin suggest it may decrease breast density, an accepted biomarker of breast cancer risk.
- Thompson, P. A., Ashbeck, E. L., Roe, D. J., Fales, L., Buckmeier, J., Wang, F., Bhattacharyya, A., Hsu, C., Chow, H. H., Ahnen, D. J., Boland, C. R., Heigh, R. I., Fay, D. E., Hamilton, S. R., Jacobs, E. T., Martinez, M. E., Alberts, D. S., & Lance, P. (2016). Selenium Supplementation for Prevention of Colorectal Adenomas and Risk of Associated Type 2 Diabetes. Journal of the National Cancer Institute, 108(12).More infoSelenium supplementation may help to prevent colorectal cancer; as precursors of colorectal cancer, colorectal adenomas are a surrogate for colorectal cancer. Selenium supplementation may increase risk of type 2 diabetes (T2D).
- Thompson, P. A., Ashbeck, E. L., Roe, D. J., Fales, L., Buckmeier, J., Wang, F., Bhattacharyya, A., Hsu, C., Chow, S. H., Ahnen, D. J., Boland, C. R., Heigh, R. I., Fay, D. E., Hamilton, S. R., Jacobs, E. T., Martinez, E. M., Alberts, D. S., & Lance, P. (2016). Celecoxib for the Prevention of Colorectal Adenomas: Results of a Suspended Randomized Controlled Trial. Journal of the National Cancer Institute, 108(12).More infoCyclooxygenase (COX)-2 inhibitors such as celecoxib were designed to preserve anti-inflammatory activity without inhibiting COX-1. Downregulation of COX-2 inhibits colorectal carcinogenesis.
- Aldaham, S., Foote, J. A., Chow, H. S., & Hakim, I. A. (2015). Smoking status effect on inflammatory markers in a randomized trial of current and former heavy smokers. International Journal of Inflammation, 2015, 6 pages. doi:10.1155/2015/439396
- 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.More infoLaboratory 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
- Miller, J. A., Pappan, K., Thompson, P. A., Want, E. J., Siskos, A. P., Keun, H. C., Wulff, J., Hu, C., Lang, J. E., & Chow, H. S. (2015). Plasma metabolomic profiles of breast cancer patients after short-term limonene intervention. Cancer prevention research (Philadelphia, Pa.), 8(1), 86-93.More infoLimonene is a lipophilic monoterpene found in high levels in citrus peel. Limonene demonstrates anticancer properties in preclinical models with effects on multiple cellular targets at varying potency. While of interest as a cancer chemopreventive, the biologic activity of limonene in humans is poorly understood. We conducted metabolite profiling in 39 paired (pre/postintervention) plasma samples from early-stage breast cancer patients receiving limonene treatment (2 g QD) before surgical resection of their tumor. Metabolite profiling was conducted using ultra-performance liquid chromatography coupled to a linear trap quadrupole system and gas chromatography-mass spectrometry. Metabolites were identified by comparison of ion features in samples to a standard reference library. Pathway-based interpretation was conducted using the human metabolome database and the MetaCyc database. Of the 397 named metabolites identified, 72 changed significantly with limonene intervention. Class-based changes included significant decreases in adrenal steroids (P < 0.01), and significant increases in bile acids (P ≤ 0.05) and multiple collagen breakdown products (P < 0.001). The pattern of changes also suggested alterations in glucose metabolism. There were 47 metabolites whose change with intervention was significantly correlated to a decrease in cyclin D1, a cell-cycle regulatory protein, in patient tumor tissues (P ≤ 0.05). Here, oral administration of limonene resulted in significant changes in several metabolic pathways. Furthermore, pathway-based changes were related to the change in tissue level cyclin D1 expression. Future controlled clinical trials with limonene are necessary to determine the potential role and mechanisms of limonene in the breast cancer prevention setting.
Proceedings Publications
- Tseng, H., Fu, Z., Chiang, J. A., Chow, H., & Vedantham, S. (2023). Patient-specific mean glandular dose from a high-resolution dedicated cone-beam breast CT system with offset detector.. In Medical Physics 50-6, 2023 AAPM Meeting Program.
- Vedantham, S., Tseng, H., Centuori, S. M., Garcia, D. O., Chalasani, P., Chiang, J. A., Roe, D., & Chow, H. (2023). Feasibility of quantitative breast density measurements in obese women with dedicated cone-beam breast CT.. In 2023 Program of the 10th International Breast Density & Cancer Risk Assessment Workshop, a21.
- Vedantham, S., Tseng, H., Fu, Z., & Chow, H. (2023). Reproducibility of volumetric fibroglandular fraction in dedicated cone-beam breast CT.. In 2023 Program of the 10th International Breast Density & Cancer Risk Assessment Workshop, a10.
Poster Presentations
- Algotar, A., Marrero, D., Chow, H., Babiker, H. M., Dougherty, S. T., Hsu, C., Smith, T., & Thomson, C. A. (2018, Fall). Abstract: Comprehensive lifestyle improvement program for prostate cancer (CLIPP) Survivors. UACC Scientific Retreat. Tucson, AZ.
- Trujillo, J. S., Villa-Guillen, D. E., Tapia, E., Cordova, C., Chalasani, P., Thomson, C. A., Altbach, M., Gallons, J. P., Miller, J., Roe, D., Algotar, A., & Chow, H. (2018, March 2018). The potential for metformin to reduce obesity-associated breast cancer risk. American Society for Preventive Oncology, 42nd Annual Conference. New York: American Society for Preventive Oncology.
- Trujillo, J., Tapia, E. O., Villa Guillen, D. E., Chalasani, P., Martinez, J. A., Guillen-Rodriguez, J. M., Thomson, C. A., Roe, D., Galons, J., Altbach, M. I., Algotar, A., & Chow, H. (2018, Fall). Abstract: Phase II clinical study of metformin for breast cancer prevention. UACC Scientific Retreat. UACC Scientific Retreat. Tucson, AZ.