Shona T Dougherty

Interests

No activities entered.

Courses

Scholarly Contributions

Books

• Zembala, M., & Asherson, G. (1989). Human monocytes. Academic Press.

Journals/Publications

• Dougherty, S. T. (2023). Symptomatic Hepatoduodenal Adenomas treated with Conventional Radiotherapy in a Patient with Familial Adenomatous Polyposis: A Case Report. Advances in Radiation Oncology, 8(3), 101181. doi:10.1016\j.adro.2023.101181
  More info

  Familial adenomatous polyposis is an inherited autosomal-dominant syndrome resulting from germline mutations in the APC gene, which predisposes patients to an extremely high risk of developing colorectal cancer throughout their lives. Although prophylactic colectomy reduces the lifetime risk of colorectal cancer development, patients remain at elevated risk of extracolonic manifestations, such as formation of adenomas throughout the upper gastrointestinal tract. Although these lesions may be benign or malignant, patients can develop significant adverse sequelae from growing adenomas via mass effect on nearby structures and often require procedural intervention. Radiation therapy (RT) has been used in the definitive and palliative settings for a variety of gastrointestinal and hepatobiliary malignancies; however, its potential utility for benign duodenal adenomas remains unclear. Here, we describe our results of using conventionally fractionated RT for 2 symptomatic hepatoduodenal adenomas causing severe abdominal pain.
• Algotar, A., Hsu, C., Chow, H., Dougherty, S. T., Babiker, H. M., Marrero, D., Abraham, I. L., Kumar, R., Ligibel, J. A., Courneya, C. S., Smith, T. E., Jones, P. A., Lopes, J., Niemiro, G., Ramakumar, S., Hoy, R., Mack, C., & Thomson, C. A. (2021). Comprehensive Lifestyle Improvement Program for Prostate Cancer (CLIPP) is associated wth improvement in weight and components of metabolic syndrome in men on androgen deprivation therapy for prostate cancer. Prostate Cancer and Prostatic Diseases, 24(3), 903-909. doi:10.1038/s41391-021-00346-z
• Goyal, U. D., Mehta, P. P., Samreth, S., Gloss, J., Cui, H., Roe, D., & Dougherty, S. (2021). Reproducibility of vaginal immobilization balloons overnight for cervical cancer brachytherapy. Journal of contemporary brachytherapy, 13(3), 280-285.
  More info

  The use of vaginal immobilization balloons placed into the vagina for immobilization of tandem and ovoid (T+O) applicator during high-dose-rate (HDR) brachytherapy delivery has been used at our institution, and seems to have improved our patient comfort, decreased procedure time, and minimized applicator misplacement. We aimed to show that these balloons, while originally marketed for single-day use, are safe and maintain applicator positioning/dosimetry when left overnight for treatment delivery on sequential days.
• Thomson, C. A., Algotar, A., Kumar, R., Ligibel, J. A., Abraham, I. L., Babiker, H. M., Courneya, C. S., Dougherty, S. T., Marrero, D., Hsu, C., Smith, T. E., Chow, H., Smith, T. E., Chow, H., Hsu, C., Marrero, D., Courneya, C. S., Dougherty, S. T., Babiker, H. M., , Abraham, I. L., et al. (2021). Protocol for a feasibility study and early efficacy study of a Comprehensive Lifestyle Improvement Program for Prostate Cancer-2 (CLIPP2).. Contemporary Clinical Trials Communications, 21, 100701.
• Thomson, C. A., Mack, C., Hoy, R., Ramakumar, S., Niemiro, G., Lopes, J., Jones, P. A., Smith, T. E., Courneya, C. S., Ligibel, J. A., Kumar, R., Abraham, I. L., Marrero, D., Babiker, H. M., Dougherty, S. T., Chow, H., Hsu, C., & Algotar, A. (2020). Comprehensive Lifestyle Improvement Program for Prostate Cancer (CLIPP) is associated wth improvement in weight and components of metabolic syndrome in men on androgen deprivation therapy for prostate cancer. Prostate Cancer and Prostatic Diseases.
• Dougherty, S. T. (2020). Prospective Study of Utilization of Edmonton Symptom Assessment Scales versus Routine Symptom Management During Weekly Radiation Treatment Visits. JCO Practical Oncology, 16(9), e1029-e1035. doi:doi: 10.1200/JOP.19.00465.
• Goyal, U. D., Riegert, K., Davuluri, R., Ong, S., Yi, S. K., Dougherty, S. T., & Hsu, C. C. (2020). Prospective Study of Use of Edmonton Symptom Assessment Scale Versus Routine Symptom Management During Weekly Radiation Treatment Visits. JCO oncology practice, 16(9), e1029-e1035.
  More info

  During radiotherapy (RT), patient symptoms are evaluated and managed weekly during physician on-treatment visits (OTVs). The Edmonton Symptom Assessment Scale (ESAS) is a 9-symptom validated self-assessment tool for reporting common symptoms in patients with cancer. We hypothesized that implementation and physician review of ESAS during weekly OTVs may result in betterment of symptom severity during RT for certain modifiable domains.
• Mostafaei, F., Dougherty, S. T., & Hamilton, R. J. (2020). Preliminary Clinical Evaluation of Intrafraction Prostate Displacements for Two Immobilization Systems. Cureus, 12(9), e10206.
  More info

  Immobilization systems and their corresponding set-up errors influence the clinical target volume to the planning target volume (CTV-PTV) margins, which is critical for hypofractionated prostate stereotactic body radiotherapy (SBRT). This preliminary study evaluates intrafraction prostate displacement for two immobilization systems (A and B). Six consecutive patients having localized prostate cancer and implanted prostate marker seeds were studied. Planar X-ray images were acquired pre- and post-treatment to find the intrafraction prostate displacement. The average absolute displacements (lateral, longitudinal, vertical) were 0.9 ± 0.4 mm, 1.7 ± 0.1 mm, 1.3 ± 0.3 mm (system A), and 0.5 ± 0.2 mm, 0.6 ± 0.1 mm, 0.8 ± 0.3 mm (system B), with average three-dimensional displacements of 2.6 ± 0.2 mm (system A) and 1.3 ± 0.2 mm (system B). The computed CTV-PTV margins (lateral, longitudinal, vertical) were 2.5 mm, 2.5 mm, 3.6 mm and 1.4 mm, 1.6 mm, 2.4 mm for systems A and B, respectively. This suggests that the immobilization system influences intrafraction prostate displacement and, therefore, the margins applied. However, the margins found for both systems are comparable to the margins used for hypofractionated prostate SBRT.
• Algotar, A., Hsu, C. H., Sherry Chow, H. H., Dougherty, S., Babiker, H. M., Marrero, D., Abraham, I., Kumar, R., Ligibel, J., Courneya, K. S., & Thomson, C. (2019). Comprehensive Lifestyle Improvement Program for Prostate Cancer (CLIPP): Protocol for a Feasibility and Exploratory Efficacy Study in Men on Androgen Deprivation Therapy. JMIR research protocols, 8(2), e12579.
  More info

  Androgen deprivation therapy (ADT) for prostate cancer is associated with adverse cardiometabolic effects such as reduced libido, hot flashes, metabolic syndrome, diabetes, myocardial infarction, and stroke. This reduces quality of life and potentially increases mortality. Several large clinical trials have demonstrated improvements in cardiometabolic risk with comprehensive multimodality lifestyle modification. However, there is a lack of data for such interventions in men on ADT for prostate cancer, and existing studies have used non-standardized interventions or lacked data on metabolic risk factors.
• Dougherty, S. T. (2019). Comprehensive Lifestyle Improvement Program for Prostate Cancer (CLIPP): Protocol for a Feasibility and Exploratory Efficacy Study in Men on Androgen Deprivation Therapy. JMIR Research Protocols, 8(2). doi:doi: 10.2196/12579.
• Dougherty, S. T. (2019). Comprehensive lifestyle improvement program for prostate cancer (CLIPP): Protocol for a feasibility and exploratory efficacy study in men on androgen deprivation therapy. JMIR - Journal of Medical Internet Research.
  More info

  Comprehensive lifestyle improvement program for prostate cancer (CLIPP): Protocol for a feasibility and exploratory efficacy study in men on androgen deprivation therapyBackground: Androgen deprivation therapy (ADT) for prostate cancer (PCa) is associated with adverse cardio-metabolic effects such as reduced libido, hot flashes, metabolic syndrome, diabetes, myocardial infarction and stroke. This reduces quality of life (QoL) and potentially increases mortality. Several large clinical trials have demonstrated improvements in cardio-metabolic risk with comprehensive multi-modality lifestyle modification. However, there is paucity of data for such interventions in men on ADT for PCa and existing studies have used non-standardized interventions or lacked data on metabolic risk factors. Comprehensive Lifestyle Improvement Project for Prostate Cancer (CLIPP), is designed to address these gaps by using an intervention modelled after The Diabetes Prevention Program (DPP), a standardized multi-component intervention with demonstrated effectiveness in reducing cardio-metabolic risk factors that has been successfully adapted for multiple disease types including breast cancer.Methods: A single-arm unblinded clinical trial will be conducted to determine the feasibility of conducting a 24-week comprehensive lifestyle modification intervention (CLMI) modelled on the DPP in 30 men on ADT for PCa. Secondary aims are to determine the effect of CLMI on cardio-metabolic markers and QoL. The tertiary aim is to determine the effect of CLMI on markers of inflammation and angiogenesis, important mechanisms for PCa progression. Participants will be recruited from the University of Arizona Cancer Center and the surrounding community. The intervention will be delivered weekly in-person and over the telephone for 16 weeks. For weeks 16 through 24, participants will receive weekly phone calls from the study health coach to motivate them to continue their CLMI. Questionnaire and biological data are collected at baseline, 12 and 24 weeks. Body composition using Dual-energy x-ray absorptiometry (DXA) scans will be performed at baseline and end of study. The CLIPP study will provide data regarding the feasibility and early efficacy of DPP style CLMI in men with ADT for PCa. Results will inform the development of future clinical trials in this population.
• Pawar, S. C., Dougherty, S., Pennington, M. E., Demetriou, M. C., Stea, B. D., Dorr, R. T., & Cress, A. E. (2007). alpha6 integrin cleavage: sensitizing human prostate cancer to ionizing radiation. International journal of radiation biology, 83(11-12), 761-7.
  More info

  The goal was to determine if prostate tumor cells containing a mutant alpha6 integrin would be defective in tumor re-population following clinically relevant fractionated ionizing radiation (IR) treatments.
• Skrepnik, T., Dougherty, S., Odunsi, K., & Pejovic, T. (2014). Principles of Radiation Therapy for Uterine Cancers. GYNECOLOGIC CANCERS: A MULTIDISCIPLINARY APPROACH TO DIAGNOSIS AND MANAGEMENT, 67-72.
• Dougherty, S. T., & Dougherty, G. J. (2011). Mechanisms Conferring Resistance to Pro-Apoptotic Cancer Gene Therapy. Journal of Cell Death, 4, 19--30.
• Dougherty, G. J., & Dougherty, S. T. (2009). Exploiting the tumor microenvironment in the development of targeted cancer gene therapy. Cancer gene therapy, 16(3), 279-90.
  More info

  The future success of cancer gene therapy is critically dependent upon the development of safe, practical and effective targeting strategies. In this study, we describe a novel and broadly applicable targeting approach in which the induction of apoptotic tumor cell death is linked to the differential expression within the tumor microenvironment of elevated levels of the pro-angiogenic cytokine vascular endothelial growth factor (VEGF). As VEGF is generally absent or produced at only low levels in most normal tissues, undesirable toxicity will not result even if the therapeutic gene in question is inadvertently expressed in non-targeted tissue sites. The basic approach makes use of a chimeric cell-surface protein in which the membrane-spanning and cytoplasmic 'death domain' of the pro-apoptotic protein Fas are fused in frame to the extracellular ligand-binding domain of the VEGF receptor Flk-1/KDR/VEGFR2 (Flk-1/Fas). The resultant chimeric Flk-1/Fas receptor was found to be stable and capable of inducing a rapid apoptotic response when expressed in tumor cells that produce endogenous VEGF. Importantly, in the absence of VEGF, transduced tumor cells remain viable although they can be triggered to die by the addition of recombinant VEGF. Given the key role played by VEGF in tumor development and progression, it is proposed that the Flk-1/Fas chimera may have great potential in the context of tumor cell-targeted cancer gene therapy.
• Dougherty, S. T., & Dougherty, G. J. (2009). A Cancer Gene Therapy Approach that Targets Tumor-associated Hyaluronan. Cancer Growth and Metastasis, 2, 29--43.
• Dougherty, S. T., Walker, S. E., Davis, P. D., & Dougherty, G. J. (2009). The Novel Vascular Disrupting Agent ANG501 Induces Cell Cycle Arrest and Enhances Endothelial Cell Sensitivity to Radiation. Cancer Growth and Metastasis, 2, 1--10.
• Dougherty, G. J., Davis, P. D., & Dougherty, S. T. (2004). Vascular-targeted cancer gene therapy. Expert opinion on biological therapy, 4(12), 1911-20.
  More info

  As a consequence of the dramatic progress that has been made in recent years towards elucidating the diverse molecular events involved in the development and pathogenesis of malignant disease, there is now no shortage of genes that can be exploited or targeted in the context of cancer gene therapy. Many of these have been shown to be effective both in vitro and in various animal models, and a number have progressed to the clinic. The results of these later studies, although generally encouraging, are perhaps less dramatic than one might have hoped. Although a number of factors undoubtedly contribute to this finding, it is evident that a major reason relates to the difficulties implicit in achieving efficient in vivo gene transfer, particularly in a clinical context. Targeting gene therapy, not to the malignant population, but instead to the vasculature upon which the survival and growth of a tumour depends constitutes an alternative approach that overcomes some of the delivery problems associated with established tumour cell-directed strategies.
• Hayes, G. M., Dougherty, S. T., Davis, P. D., & Dougherty, G. J. (2004). Molecular mechanisms regulating the tumor-targeting potential of splice-activated gene expression. Cancer gene therapy, 11(12), 797-807.
  More info

  Previous studies have suggested that differences in the ability of normal and malignant cells to process certain alternatively spliced pre-mRNA transcripts can be exploited as a potentially powerful means of targeting the expression of therapeutic genes to tumor cells in vivo and in vitro. Specifically, it was shown that efficient processing of minigene constructs containing the alternatively spliced CD44 exons v9 and v10 only occurs in tumor cells that express CD44 isoforms that incorporate these exons (e.g. CD44R1). In the present study, efforts were made to define the molecular mechanisms that underlie the apparent specificity of this process. RT-PCR analysis and DNA sequencing were used to characterize the various splicing events that occur between CD44 exons v8, v9 and v10 following transfection of minigene constructs containing these various exons into CD44R1-positive (PC3) and CD44R1-negative (T24) cell lines. The results obtained confirm that although the v8-v9 intron is efficiently removed in both CD44R1-positive and CD44R1-negative cells, the corresponding v9-v10 intron is accurately spliced and the exons appropriately joined only in lines that express v10-containing CD44 isoforms (e.g. PC3). In CD44R1-negative cell lines (e.g. T24) alternative 5' and 3' splice sites located within the v9-v10 intron are preferentially used, resulting in various portions of the intron being retained within the final processed mRNA product. It is proposed that identification of these functionally important intronic sequence elements will facilitate the development of second generation "splice activated gene expression" vectors that may prove useful in various cancer gene therapy applications.
• Carpenito, C., Davis, P. D., Dougherty, S. T., & Dougherty, G. J. (2002). Exploiting the differential production of angiogenic factors within the tumor microenvironment in the design of a novel vascular-targeted gene therapy-based approach to the treatment of cancer. International journal of radiation oncology, biology, physics, 54(5), 1473-8.
  More info

  The aim of this study is to explore a novel strategy through which the differential production of pro-angiogenic cytokines within the tumor microenvironment can be exploited as a means of selectively killing the vascular endothelial cells upon which the survival and growth of a tumor depend.
• Hayes, G. M., Carpenito, C., Davis, P. D., Dougherty, S. T., Dirks, J. F., & Dougherty, G. J. (2002). Alternative splicing as a novel of means of regulating the expression of therapeutic genes. Cancer gene therapy, 9(2), 133-41.
  More info

  In order to determine the potential of alternative splicing as a means of targeting the expression of therapeutic genes to tumor cells in vivo, a series of episomal plasmid-based "splice-activated gene expression" (pSAGE) vectors was generated, which contain minigene cassettes composed of various combinations of the three alternatively spliced exons present in the differentially expressed adhesion protein CD44R1 (v8, v9, and v10) with or without their corresponding intronic sequences, positioned in-frame between the CD44 leader sequence and a "leaderless" human liver/bone/kidney alkaline phosphatase (ALP) cDNA. Because both the v8-v9 and v9-v10 introns contain multiple in-frame stop codons, the expression and enzymatic activity of ALP are dependent upon the accurate removal of intronic sequences from the pre-mRNA transcripts encoded by these constructs. The various pSAGE constructs were introduced into CD44H-positive (T24) and CD44R1-positive (PC3) target cells by electroporation and transfectants selected in hygromycin B. ALP expression was determined by staining with the ALP substrate, BCIP/INT, and the transfected cells tested for their sensitivity to the inactive prodrug, etoposide phosphate. ALP-mediated dephosphorylation of etoposide phosphate generates the potent topoisomerase II inhibitor etoposide. The data obtained indicate that whereas the v8-v9 intron is spliced in both CD44H- and CD44R1-positive cells, the v9-v10 intron is efficiently and accurately removed only in CD44R1-positive cells. Furthermore, only CD44R1-positive cells were sensitized to etoposide phosphate when transfected with the v9-v10.ALP construct. These data emphasize the potential usefulness of alternative splicing as a novel means of targeting gene expression to tumor cells in vivo.
• Hayes, G. M., Chiu, R., Carpenito, C., Dougherty, S. T., & Dougherty, G. J. (2002). Identification of sequence motifs responsible for the adhesive interaction between exon v10-containing CD44 isoforms. The Journal of biological chemistry, 277(52), 50529-34.
  More info

  Previous studies have demonstrated that CD44 isoforms containing the alternatively spliced exon v10 promote cell-cell adhesion via a mechanism that involves the recognition of chondroitin sulfate side chains presented on the surface of interacting cells in association with other CD44 molecules. Sequence analysis revealed the presence within exon v10 of two motifs that may be relevant to this interaction, a B[X(7)]B motif that may contribute to the recognition and binding of chondroitin sulfate and a serine-glycine motif that may serve as a site of chondroitin sulfate attachment. To determine whether either of these two motifs explain the unique adhesive activity of exon v10-containing CD44 isoforms, each was targeted by site-directed mutagenesis, and the adhesive activity of the resultant mutants was determined using a quantitative cell-cell binding assay. The data obtained demonstrate conclusively that it is the exon v10-encoded B[X(7)]B motif that is solely responsible for the enhanced adhesive activity of exon v10-containing CD44 isoforms.
• Chiu, R. K., Carpenito, C., Dougherty, S. T., Hayes, G. M., & Dougherty, G. J. (1999). Identification and characterization of CD44RC, a novel alternatively spliced soluble CD44 isoform that can potentiate the hyaluronan binding activity of cell surface CD44. Neoplasia (New York, N.Y.), 1(5), 446-52.
  More info

  Soluble CD44 proteins generated by proteolytic cleavage or aberrant intron retention have been shown to antagonize the ligand binding activity of the corresponding cell surface receptor, inducing apoptosis and inhibiting tumor growth. Interestingly, such findings appear to contradict recent studies demonstrating a correlation between the presence of high levels of soluble CD44 in the serum of cancer patients and poor prognosis. In the present study, we report the cloning of a novel, naturally occurring, differentially expressed, soluble CD44 isoform, designated CD44RC, which, in contrast to previously described soluble CD44 proteins, can dramatically enhance the hyaluronan binding activity of cell surface CD44. Sequence analysis suggests that CD44RC is generated by an alternative splicing event in which the 3' end of CD44 exon 2 is spliced into an internal splice acceptor site present within exon 18, altering reading frame and giving rise to a soluble protein with a unique COOH terminus. Functional studies suggest that CD44RC enhances hyaluronan binding by adhering to chondroitin sulfate side-chains attached to cell surface CD44, generating a multivalent complex with increased avidity for hyaluronan.
• Chiu, R. K., Droll, A., Dougherty, S. T., Carpenito, C., Cooper, D. L., & Dougherty, G. J. (1999). Alternatively spliced CD44 isoforms containing exon v10 promote cellular adhesion through the recognition of chondroitin sulfate-modified CD44. Experimental cell research, 248(1), 314-21.
  More info

  Correlations have been noted between the expression of certain alternatively spliced CD44 isoforms and the metastatic propensity of various histologically distinct tumor cell types. The precise mechanism by which particular CD44 isoforms contribute to the metastatic process is, however, unclear. In the present study we demonstrate that CD44R2, a CD44 isoform highly expressed on activated and transformed hemopoietic cells, can recognize and bind a common determinant present on CD44H and CD44R1. Importantly, CD44H lacked this activity. Pretreatment of TIL1 cells expressing CD44H or CD44R1 with chondroitinase ABC inhibited adhesion to CD44R2, suggesting that the unique inserted region present within the CD44R2 molecule, encoded by exon v10, mediates cell adhesion by potentiating the recognition of chondroitin sulfate moieties presented in association with other CD44 molecules. These data help explain the differential involvement of v10-containing CD44 isoforms in tumor metastasis.
• Renschler, M. F., Yuen, A. R., Panella, T. J., Wieman, T. J., Dougherty, S., Esserman, L., Panjehpour, M., Taber, S. W., Fingar, V. H., Lowe, E., Engel, J. S., Lum, B., Woodburn, K. W., Cheong, W., & Miller, R. A. (1998). Photodynamic therapy trials with lutetium texaphyrin (Lu-Tex) in patients with locally recurrent breast cancer. Proc. SPIE, 3247, 35-39.
• Safa, A. A., Reese, D. M., Carter, D. M., Phillipson, J., Smith, R., & Dougherty, S. (1998). Undetectable serum prostate-specific antigen associated with metastatic prostate cancer: a case report and review of the literature. American journal of clinical oncology, 21(4), 323-6.
  More info

  A 63-year-old man, who had undergone prostatectomy for prostate cancer that was positive for prostate-specific antigen (PSA) was examined and found to have metastatic disease, proven radiologically and pathologically, but with an undetectable PSA and highly elevated prostatic acid phosphatase (PAP). Prostatic acid phosphatase levels fell in response to chemotherapy but his clinical status continued to deteriorate. A review of the literature is presented and several possible explanations for PSA remaining undetectable in these situations are discussed. The authors conclude that although PSA can be used to monitor the majority of patients postprostatectomy, physicians may still need to rely on clinical suspicion, serum PAP, and bone scan for the detection of recurrent disease.
• Dougherty, S. T., Eaves, C. J., McBride, W. H., & Dougherty, G. J. (1997). Molecular mechanisms regulating TNF-alpha production by tumor-associated macrophages. Cancer letters, 111(1-2), 27-37.
  More info

  The molecular mechanisms that regulate the production and/or functional activity of intratumoral tumor necrosis factor-alpha (TNF-alpha) remain poorly defined. To begin to address this issue we have examined the level of TNF-alpha mRNA and protein produced by macrophages present within immunogenic Fsa-R and non-immunogenic Fsa-N tumors grown in syngeneic Lps(d) C3H/HeJ and Lps(n) C3H/HeN mice. The results obtained indicate that macrophages isolated from tumors grown in Lps(d) C3H/HeJ mice express 5-10-fold less TNF-alpha than equivalent cells present in tumors grown in Lps(n) C3H/HeN mice. These data suggest that the mechanisms that operate within the tumor microenvironment to induce the production of TNF-alpha act, at least in part, via the same signal transduction pathway that is defective in Lps(d) C3H/HeJ mice. Interestingly, despite such differences in TNF-alpha production, tumors inoculated into C3H/HeJ and C3H/HeN mice grew at a similar rate and contained an almost identical proportion of macrophages. Moreover, tumor cells purified from tumors grown in C3H/HeJ and C3H/HeN mice produced similar quantities of the TNF-alpha-inducible cytokine GM-CSF. Thus, although differences in the level of TNF-alpha produced within tumors grown in C3H/HeN and C3H/HeJ mice are readily demonstrable, such differences appear to have little direct impact on the outcome of tumor growth.
• Dougherty, S. T., Eaves, C. J., McBride, W. H., & Dougherty, G. J. (1997). Role of macrophage-colony-stimulating factor in regulating the accumulation and phenotype of tumor-associated macrophages. Cancer immunology, immunotherapy : CII, 44(3), 165-72.
  More info

  In order to better define the role played by tumor-cell-derived macrophage-colony-stimulating factor (M-CSF) in regulating the recruitment and phenotype of tumor-associated macrophages, Polyoma large T-transformed fibroblastoid cell lines, derived from M-CSF-deficient osteopetrotic op/op mice and their phenotypically normal op/+ littermate controls, were inoculated into SCID (severe combined immunodeficiency) recipients and both the proportion and phenotype of the macrophages present within the tumors generated were determined. The results obtained indicate that, although tumors derived from M-CSF-deficient and M-CSF-producing tumor cell inoculate contain a similar proportion of macrophages, the macrophages isolated from tumors lacking M-CSF appear morphologically less mature and express lower levels of interleukin 1 beta, tumor necrosis factor alpha and FcR gamma II mRNA. Taken together, these data suggest that, although M-CSF does not appear to play a critical role in determining the macrophage content of these tumors, it does play a role in modulating the phenotype, and potentially the functional activity of the macrophages present within the tumor microenvironment.
• Dougherty, G., Chaplin, D., Dougherty, S., Chiu, R., & McBride, W. (1996). In vivo gene therapy of cancer. Tumor Targeting, 2, 1--10.
• Dougherty, S. T. (1996). gene therapy-based approaches to the treatment of cancer. Transfusion Science, 17, 121-128. doi:0915-7352
• Chiu, R. K., Droll, A., Cooper, D. L., Dougherty, S. T., Dirks, J. F., & Dougherty, G. J. (1995). Molecular mechanisms regulating the hyaluronan binding activity of the adhesion protein CD44. Journal of neuro-oncology, 26(3), 231-9.
  More info

  In the present study, we describe the isolation and characterization of a cDNA clone designated B6F1.3, that appears to 'activate' the hyaluronan-binding capacity of CD44 upon transfection into the murine fibroblastoid cell line MOP8. Sequence analysis indicates that the putative regulatory molecule encoded by this clone is identical to the murine interleukin-2 receptor gamma chain (mIL-2R gamma), a recently described type 1 transmembrane protein that constitutes an integral component of the cell surface receptors that bind a number of cytokines including IL-2, IL-4, IL-7, IL-9, IL-15 and perhaps also IL-13. Mutations in this molecule have been shown to be responsible for X-linked severe combined immunodeficiency (XSCID) in humans. With the exception of bone marrow, the mIL-2R gamma chain was found to be expressed at high levels on all hemopoietic cell lines and tissue types examined. Non-hemopoietic tissues are generally negative. FACS analysis and Western blot analysis indicated respectively that B6F1.3 does not mediate its effects by upregulating the expression of CD44 or by altering the alternative splicing of the molecule. Removal of the cytoplasmic tail of the mIL-2R gamma chain, including a Src homology region 2 (SH2) subdomain, abolished its ability to enhance CD44-mediated binding to hyaluronan suggesting the involvement of signal transduction events triggered via the cytoplasmic domain in the 'activation' process. Determining whether activating molecules such as B6F1.3 are co-expressed within tumor cells may help improve the potential value of CD44 as a diagnostic marker of metastatic disease.
• Dougherty, G., Dougherty, S., Dirks, J., Chui, R., Peters, C., Droll, A., & author_in_Japanese, . (1995). Regulation of the Functional Activity and Ligand Binding Specificity of the Adhesion Protein CD44. Trends in Glycoscience and Glycotechnology, 7, 45-56.
• Droll, A., Dougherty, S. T., Chiu, R. K., Dirks, J. F., McBride, W. H., Cooper, D. L., & Dougherty, G. J. (1995). Adhesive interactions between alternatively spliced CD44 isoforms. The Journal of biological chemistry, 270(19), 11567-73.
  More info

  Alternative splicing of a series of 10 contiguous exons present within the CD44 gene can generate a large number of differentially expressed CD44 isoforms that contain additional peptide sequences of varying length inserted into a single site within the extracellular domain of the molecule proximal to the membrane spanning domain. Although distinct functions have been ascribed to certain of these isoforms, the effect of particular inserted domains on the ligand-binding specificity of the CD44 molecule remains unclear. In the present study, we demonstrate that while CD44H, the major CD44 isoform expressed on resting hemopoietic cells, and CD44R1, an alternatively spliced isoform present on transformed epithelial cells and certain activated and/or malignant hemopoietic cell types, can both bind avidly to hyaluronan, only CD44R1 can promote homotypic cellular aggregation when expressed in the CD44-negative murine lymphoma cell line TIL1. Experiments in which TIL1 cells transduced with different CD44 isoforms were tested for their ability to adhere to one another or to COS7 cells transfected with CD44R1, indicated that CD44R1 can recognize and bind a common determinant present on both CD44H and CD44R1. Monoclonal antibody blocking studies suggest further, that the determinant recognized by CD44R1 is located in a region of the CD44 molecule distinct from that involved in hyaluronan binding.
• McBride, W. H., Economou, J. S., Kuber, N., Hong, J. H., Chiang, C. S., Syljuasen, R., Dougherty, S. T., & Dougherty, G. J. (1995). Modification of tumor microenvironment by cytokine gene transfer. Acta oncologica (Stockholm, Sweden), 34(3), 447-51.
  More info

  The tumor microenvironment is determined by the interactions between host and tumor cells, a process in which cytokines play a major role. We have used retroviral vectors to insert and express cytokine genes in tumor cells so as to induce predictable changes in the host cells that infiltrate tumors. This frequently caused changes in tumor cell phenotype through autocrine/intracrine pathways. We reasoned that cytokine-induced alterations in tumor cell phenotype and/or in infiltrating host cells might alter the in vitro and in vivo cellular response to irradiation. In the present paper we document some of the effects of expression of interleukin-6 (IL-6) and IL-7 genes in tumor cells in this regard. The studies support the hypothesis that cytokines may play a role in determining both intrinsic tumor radioresponsiveness and the tumor microenvironment and in these ways may influence in vivo tumor irradiation responses. Possible cytokine gene-mediated approaches to radiotherapy cancer are discussed.
• Dougherty, G. J., Dougherty, S. T., Kay, R. J., Landsdorp, P., & Humphries, R. K. (1989). Identification and characterization of 114/A10, an antigen highly expressed on the surface of murine myeloid and erythroid progenitor cells and IL-3-dependent cell lines. Experimental hematology, 17(8), 877-82.
  More info

  Monoclonal antibody (mAb) 114/A10, raised against the murine bone marrow-derived multipotential hemopoietic progenitor cell line B6SUtA, identifies an antigen highly expressed by various interleukin-3 (IL-3)-dependent cell lines, the myelomonocytic cell line WEHI-3, and a large proportion of primary myeloid and erythroid colony-forming cells. Spleen- and bone marrow-derived 114/A10-positive cells were shown to selectively proliferate in vitro in response to pokeweed mitogen-stimulated spleen cell-conditioned medium or recombinant IL-3. Western blot analysis indicated that the antigen recognized by mAb 114/A10 has a mean relative molecular mass of approximately 150,000, although it is extremely heterogeneous in nature, and differs greatly in size range among different cell lines.
• Marks, A., Goodman, A., Dougherty, S., & Ashford, R. (1987). Myelosuppression after methotrexate, mitozantrone, and mitomycin C for treatment of advanced breast cancer. Lancet (London, England), 1(8538), 915.

Poster Presentations

• Thomson, C. A., Smith, T., Hsu, C., Dougherty, S. T., Babiker, H. M., Chow, H., Marrero, D., & Algotar, A. (2018, Fall). Abstract: Comprehensive lifestyle improvement program for prostate cancer (CLIPP) Survivors. UACC Scientific Retreat. Tucson, AZ.
• Dougherty, S. T. (2016, September). Immobilization Balloons used for Specialized Brachytherapy Treatment For Cervical Cancer. ASTRO annual meeting. Boston: ASTRO.
  More info

  Inflatable balloons can be used as an alternative to traditional gauze packing for immobilization of the tandem and ovoid (T&O) apparatus during HDR brachytherapy procedures as well as for reducing the bladder and rectal doses. The aim of this study was to show that the immobilization balloons when left in place overnight during a fractionated course of brachytherapy for treatment on sequential days, are safe and reproducible.

Others

• Dougherty, S. T. (2018, October). Comprehensive Lifestyle Improvement Program for Prostate Cancer (CLIPP): Protocol for a Feasibility and Exploratory Efficacy Study in Men on Androgen Deprivation Therapy (Preprint). https://doi.org/10.2196/preprints.12579