The Genitourinary Oncology Program at the OSUCCC – James is committed to providing a range of clinical trial opportunities to our patients undergoing care for prostate, bladder, testicular, and kidney cancer. The Genitourinary Malignancies Program benefits from National Cancer Institute (NCI) support of phase I and phase II clinical trials of novel agents for cancer treatment and facilitates the movement of promising new interventions into phase III national trials that are shared among many collaborating institutions. Studies include novel approaches to surgery, pharmacologic therapy, immunology, and radiation therapy. In addition to therapeutic trails, the program offers studies of cancer prevention and survivorship.
The OSUCCC – James Genitourinary Oncology Program benefits from being fully integrated with the National Cancer Institute Designated Ohio State University (OSU) Comprehensive Cancer Center. This integration facilities the seamless interaction between basic and translational research scientists with clinical investigators. The research effort is further enhanced by unique interactions with faculty across the OSU campus fostering collaborative research that is exceptionally novel and stimulating. Collaborations with biomedical engineering stimulate the development of novel imaging to more precisely detect cancers within tissues. Colleagues in our Agricultural Sciences are developing and testing novel food products for cancer prevention in our renown “Crops to the Clinic” research program. Veterinary scientists and James investigators share expertise in understanding human prostate cancer through the study of a similar cancer in the dog, “man’s best friend” and the only other species other than humans to develop prostate cancer. Together, the OSU family of investigators strive to bring the best of cancer research to clinic in our quest to defeat cancer therough prevention and effective therapy.
The research program focuses upon the following themes:
- Multidisciplinary strategies for high risk prostate cancer integrating surgery, hormone and pharmaceutical intervention to improve rates of cure.
- Improving the delivery of conformal radiation therapy for prostate cancer through advanced technolgocial imaging and planning in combination with novel agents.
- Genetic analysis of individual cancers to define unique targets for therapeutic agents.
- Optimization of immune therapies for advanced kidney cancer and determine the ideal strategy for integration of immune therapy with multiple targeted agents currently available and in development.
- Testing of radiopharmaceuticals for metastatic cancer to bone.
- Determine the most effective and safe sequence and combination of anti-androgens during prostate cancer therapy.
- Dietary and nutritional studies designed to improve our understanding of cancer etiology in addition to defining roles for nutrients, foods, or dietary patterns to support cancer therapy.
- Improvement of performance status in men undergoing hormone therapy for prostate cancer through exercise and physical activity.
- Developing and testing novel combinations of agents for aggressive bladder cancer in combination with surgery.
- Optimizing surgical strategies for invasive bladder cancer.
- Defining histopathological and molecular biomarkers for genitourinary malignancies that improve our ability to predict treatment response and define optimal therapeutic approaches.
- Testing of strategies to improve sexual function in men following therapy for prostate and other genitourinary cancers.
Selected Clinical and Population Research Accomplishments
A phase I study of high-dose interleukin-2 with sorafenib in patients with metastatic renal cell carcinoma and melanoma.
This study by GU team physicians Drs. Thomas Olencki, J. Paul Monk, Amir Mortazavi, and Steven Clinton evaluated the safety and feasibility of high-dose interleukin-2 (HD IL-2) followed by sorafenib in patients with metastatic renal cell carcinoma (RCC). Journal of Immunotherapy, 2014.
Dietary lycopene, angiogenesis, and prostate cancer: a prospective study in the PSA era.
Dr. Clinton continues his longstanding collaborations with the Harvard School of Public Health. Their team shows a continued lower risk of prostate cancer in men consuming tomato products and defines possible molecular targets for prostate cancer prevention. Journal of the National Cancer Institute, 2014.
A phase I dose escalation and pharmacodynamic study of SU5416 (Semaxanib) combined with weekly cisplatin and irinotecan in patients with advanced solid tumors.
Dr. Clinton collaborated with multiple faculty at the OSUCCC to examine a novel antiangiogenic agent for solid tumors. Onkologie, 2013.
Effects of exercise on disablement process model outcomes in prostate cancer patients undergoing androgen deprivation therapy: a systematic review.
Dr. Clinton and Dr. Focht in OSU’s Kinesiology Department have reviewed the impact of exercise on physical performance and quality of life in men on hormone therapy. Journal of Community and Supportive Oncology, 2014.
Resistance exercise interventions during and following cancer treatment: a systematic review.
Drs. Clinton and Focht further define the role fo specific exercise strategies to improve physical performance in men with prostate cancer undergoing hormone therapy. Journal Support Oncology, 2013.
The individualized diet and exercise adherence pilot trial (IDEA-P) in prostate cancer patients undergoing androgen deprivation therapy: study protocol for a randomized controlled trial.
Dr. Clinton collaborated with Dr. Focht to establish a diet and exercise trial to improve physical performance and nutrition in men undergoing hormone therapy for prostate cancer. Trials, 2014.
Improving bladder cancer imaging using 3T functional dynamic contrast-enhanced MRI.
Drs Pohar, Mortazavi, and Zynger collaborated with Dr. Knopp of OSU’s renown imaging center to develop improved imaging for bladder cancer detection and staging prior to surgery. Investigative Radiology, 2014.
A phase I study of prolonged infusion of triapine in combination with fixed dose rate gemcitabine in patients with advanced solid tumors.
Drs. Mortazavi and Monk collaborated with The James phase I drug development team to test a new infusion strategy for one of the major bladder cancer chemotherapeutic agents. Investigational New Drugs, 2013.
Docetaxel and atrasentan versus docetaxel and placebo for men with advanced castration-resistant prostate cancer (SWOG S0421): a randomised phase 3 trial.
Dr. Monk collaborated with a national team to conduct a large phase three trial of combination chemotherapy for men with metastatic prostate cancer. The Lancet Oncology, 2013.
The effect of prior androgen synthesis inhibition on outcomes of subsequent therapy with docetaxel in patients with metastatic castrate-resistant prostate cancer: results from a retrospective analysis of a randomized phase 3 clinical trial (CALGB 90401) (Alliance).
Dr. Monk collaborated with a national team to investigate the impact of sequential hormonal and chemotherapy for men with metastatic prostate cancer. Cancer, 2013.
Randomized controlled trial of early zoledronic acid in men with castration-sensitive prostate cancer and bone metastases: results of CALGB 90202 (Alliance).
Dr. Monk and the OSU clinical team were major participants in a study to examine novel agents to improve bone health in men with metastatic prostate cancer. Journal of Clinical Oncology, 2014.
Retrospective analysis of the safety and efficacy of high-dose interleukin-2 after prior tyrosine kinase inhibitor therapy in patients with advanced renal cell carcinoma.
Drs. Olencki and Monk examined the optimal sequence of therapy for patients with metastatic renal cell carcinoma. Journal of Immunotherapy, 2014.
Phase I study of the safety and efficacy of GC1008: a human anti-transforming growth factor-beta (TGFβ) monoclonal antibody in patients with advanced renal cell carcinoma or malignant melanoma.
Dr. Olencki collaborated with a national team to study the role of a novel immunologic based therapy for metastatic kidney cancer. PLOS One, 2014.
Multimodal imaging and detection strategy with 124 I-labeled chimeric monoclonal antibody cG250 for accurate localization and confirmation of extent of disease during laparoscopic and open surgical resection of clear cell renal cell carcinoma.
Drs. Sharp, Bahnson of Urology collaborated with Dr Knopp in Radiology to examine novel technology to improve surgery for kidney cancer. Surgical Innovation, 2013.
Prostate cancer early detection, version 1.2014. Featured updates to the NCCN Guidelines.
Dr. Bahnson served on the national committee to define guidelines for prostate cancer detection. Journal of National Comprehensive Cancer Network, 2014.
NCCN guidelines for prostate cancer, therapy, version 2.2014.
Dr. Bahnson served on the national committee to define guidelines for prostate cancer therapy. Journal of National Comprehensive Cancer Network, 2014.
Hexaminolevulinate blue-light cystoscopy in non-muscle-invasive bladder cancer: review of the clinical evidence and consensus statement on appropriate use in the USA.
Dr. Pohar and colleagues developed guidelines for the use of a novel cystoscopic procedure for bladder cancer. National Review of Urology, 2014.
Challenges in the pathological reporting of urothelial carcinoma involving prostatic transurethral resection specimens within a single institution.
Dr. Pohar and Zynger described challenges and stardardization approaches to bladder cancer. Pathology, 2013.
Clinicopathologic characteristics and overall survival in patients with bladder cancer involving the gastrointestinal tract.
Dr. Pohar and Zynger described the impact of bladder cancer invading the gastrointestinal system. Virchows Archives, 2013.
The anatomic extent and completeness of pelvic lymphadenectomy is what matters.
Dr. Pohar and colleagues described how more extensive surgical removal of lymph nodes with well-defined surgical boundaries offers patients the best chance of a cure. Current Opinion in Urology, 2013.
Penile cancer: Clinical Practice Guidelines in Oncology.
Dr. Pohar contributed to this set of NCCN clinical guidelines, which offers recommendations on diagnosis and management of penile cancer. Journal of the National Comprehensive Cancer Network, 2013.
Bladder Cancer: Clinical Practice Guidelines in Oncology.
Dr. Pohar contributed to these NCCN clinical guidelines, which offers recommendations on diagnosis and management of bladder cancer. Journal of the National Comprehensive Cancer Network, 2013.
Intraductal carcinoma of the prostate: interobserver reproducibility survey of 39 urologic pathologists.
Dr. Debra Zynger and colleagues propose a universal criteria for diagnosing intraductal prostate cancer. Annals of Diagnostic Pathology, 2014.
Enhanced enrichment of prostate cancer stem-like cells with miniaturized 3D culture in liquid core-hydrogel shell microcapsules.
Dr. Zynger and colleagues developed a unique culture method to support the culture of rare populations of cancer stem cells to understand their biology an relevance to human prostate cancer therapy. Biomaterials, 2014.
Do robotic prostatectomy positive surgical margins occur in the same location as extraprostatic extension?
Dr. Zynger and others demonstrate that positive surgical margins often do not occur in the same place as extraprostatic extension, a finding that may impact surgical techniques to improve outcomes from prostatectomy. World Journal of Urology, 2014.
Bladder preservation therapy for muscle-invading bladder cancers on Radiation Therapy Oncology Group trials 8802, 8903, 9506, and 9706: vascular endothelial growth factor B overexpression predicts for increased distant metastasis and shorter survival.
Drs. Arnab Chakravarti and Lautenschlaeger demonstrate that expression of VEGF, an angiogenic factor, is significantly associated with shorter survival. Oncologist, 2013.
Comparison of microRNA deep sequencing of matched formalin-fixed paraffin-embedded and fresh frozen cancer tissues.
Drs. Arnab Chakravarti and Lautenschlaeger tested sequencing methods to quantify expression of microRNAs in order to better define tissue biomarekers to enhance our prognostic ability and better select therapy. PLOS One, 2013.
Selected Basic and Translational Research Accomplishments
Dietary tomato and lycopene impact androgen signaling- and carcinogenesis-related gene expression during early TRAMP prostate carcinogenesis.
Dr. Clinton and colleagues describe molecular mechanisms whereby bioactive phytochemicals in tomatoes may reduce the ability of testosterone to stimulate early prostate cancer. Cancer Prevention Research, 2014.
Alterations of histone H1 phosphorylation during bladder carcinogenesis.
Drs. Mortazavi, Clinton, and Zynger collaborated with basic scientists to define epigenetic mechanisms involved in bladder carcinogenesis. Journal of Proteome Research, 2013.
Increasing the complexity of chromatin: functionally distinct roles for replication-dependent histone h2a isoforms in cell proliferation and carcinogenesis.
Drs. Mortazavi and Clinton collaborated with a team of basic scientists to examine how disruption of gene expression contributes to bladder carcinogenesis. Nucleic Acids Research, 2013.
Agonist and antagonist switch DNA motifs recognized by human androgen receptor in prostate cancer.
Drs. Qianben Wang, Cassandra Grenade, Steven Clinton, Debra Zynger, Jennifer Thomas-Ahner and others demonstrate that DNA binding receptors have unique ligand mediated binding motifs and gene expression profiles associated with prostate carcinogenesis. European Molecular Biology Organization, Accepted 2014.
Three-tiered role of the pioneer factor GATA2 in promoting androgen-dependent gene expression in prostate cancer.
Dr. Wang and colleagues demonstrate that the pioneer factors in prostate cancer, FoxA1 and GATA 2, regulate androgen receptor binding and androgen-responsive gene expression profiles.Nucleic Acids Research, 2014.
Novel pharmacologic targeting of tight junctions and focal adhesions in prostate cancer cells.
Dr. Ching-Shih Chen and colleaguesgenerated a novel lead quinazoline-based Doxazosin® derivative, DZ-50, which impairs tumor growth and metastasis and characterized key mechanisms of action, supporting the therapeutic significance of this agent for the treatment of advanced prostate cancer. PLOS One, 2014.
AMPK reverses the mesenchymal phenotype of cancer cells by targeting the Akt-MDM2-Foxo3a signaling axis.
Dr. Ching-Shih Chen and his team report a novel function of the master metabolic kinase AMPK in suppressing the epithelial-mesenchymal transition by modulating the Akt-MDM2-Foxo3 signaling axis, thereby defining new targets in prostate cancer therapy. Cancer Research, 2014.
Functional role of mTORC2 versus integrin-linked kinase in mediating ser473-Akt Phosphorylation in PTEN-negative prostate and breast cancer cell lines.
Dr. Ching-Shih Chen and colleagues demonstrated the cell type specificity of integrin-linked kinase (ILK) versus mTORC2 as PDK2 (phosphoinositide-dependent kinase 2) prostate and breast cancer cells and hypothesize that ILK signaling may bestow a growth and metastatic advantage. PLOS One, 2013.
Vitamin E facilitates the inactivation of the kinase Akt by the phosphatase PHLPP1.
Dr. Ching-Shih Chen optimized derivatives α-tocopherol and γ-tocopherol to have greater potency and tumor-suppressive activity in prostate cancer models. Science Signaling, 2013.
Suppression of prostate epithelial proliferation and intraprostatic progrowth signaling in transgenic mice by a new energy restriction-mimetic agent.
Drs. Chen, Clinton, and others demonstrated the ability of a novel energy restriction-mimetic agent, OSU-CG5, to inhibit early biomarkers of cancer progression in an experimental model of prostate cancer. Cancer Prevention Research, 2013.
Biochemical characterization of prostate-specific membrane antigen from canine prostate carcinoma cells.
Dr. Thomas Rosol and colleagues demonstrate that prostate-specific membrane antigen (PSMA) is expressed in canine prostate tumor cells similarly to that in humans; therefore, prostate cancer mechanisms may be studied in a similar animal model before humans. The Prostate, 2014.
Canine prostate cancer cell line (Probasco) produces osteoblastic metastases in vivo.
Dr. Rosol and others established a novel canine prostate cell line which can be used to determine prostate cancer growth mechanisms. The Prostate, 2014.
Nanoparticulate paclitaxel demonstrates antitumor activity in PC3 and Ace-1 aggressive prostate cancer cell lines.
Dr. Rosol and others demonstrated the ability of a nanoparticle formulation to be as effective of paclitaxel in experimental models of prostate cancer. Investigational New Drugs, 2013.
Clinical Trials for Genitourinary Malignancies
OSU-07042: Imaging of the Prostate Gland Using High-Field Strength 3T MRI
NCT ID: NCT01653093
Key Objective: To determine how well MRI can identify prostate cancer prior to surgery and the correlation between imaging and histopathologic evaluation.
OSU-12008: Intensive Diet and Exercise Adherence Trial – Pilot (IDEA-P): A Feasibility Study of a Lifestyle Intervention in Men Undergoing Androgen Deprivation Therapy
NCT ID: NCT02050906
Key Objective: To establish the feasibility and effectiveness of a lifestyle diet and exercise intervention in PCa patients on hormone therapy.
ALLIANCE-A031203: A PH III Trial of Enzalutamide versus Enzalutamide, Abiraterone, and Prednisone for Castration Resistant Metastatic Prostate Cancer
NCT ID: NCT01949337
Key Objective: To compare the drug enzalutamide alone or in combination with with abiraterone and prednisone. The main outcome is overall survival of men with metastatic, castrate-resistant prostate cancer.
SWOG-S1216: A Phase III Randomized Trial Comparing Androgen Deprivation Therapy + TAK-700 with Androgen Deprivation Therapy + Bicalutamide in Patients with Newly Diagnosed Metastatic Hormone Sensitive Prostate Cancer
NCT ID: NCT01809691
Key Objective: To compare hormone therapy (luteinizing hormone-releasing hormone analogue or testicle removal) combined with the drug TAK-700 or with bicalutamide. This study is for men with newly diagnosed metastatic prostate cancer with the main outcome being overall survival.
RTOG-0534: A Phase III Trial of Short Term Androgen Deprivation with Pelvic Lymph Node or Prostate Bed Only Radiotherapy in Prostate Cancer Patients with a Rising PSA after Radical Prostatectomy
NCT ID: NCT00567580
Key Objectives: To determine if adding androgen deprivation before prostate surgery and during radiation therapy slows prostate cancer progression. This study will also investigate whether radiation to pelvic lymph nodes improves outcomes.
CALGB-90203: A Randomized Phase III Study of Neo-Adjuvant Docetaxel and Androgen Deprivation Prior to Radical Prostatectomy versus Immediate Radical Prostatectomy in Patients with High-Risk, Clinically Localized Prostate Cancer
NCT ID: NCT00430183
Key Objective: To determine if treating high-risk prostate cancer patients with chemotherapy and hormone therapy before prostate surgery as opposed to treating them with surgery alone will reduce the chance of recurrence.
OSU-08063: Imaging of the Bladder Tumor Using Clinical 3 Tesla MRI and Ex-Vivo Ultra-high-field MRI
NCT ID: NCT00938145
Key Objectives: To evaluate if a 3 Tesla MRI can correctly determine tumor and lymph node stage in bladder cancer patients. This study will also evaluate whether the MRI can correctly determine the response to pre-surgical chemotherapy.
CALGB-90601: A Randomized Double-Blinded Phase III Study Comparing Gemcitabine, Cisplatin, and Bevacizumab to Gemcitabine, Cisplatin, and Placebo in Patients with Advanced Transitional Cell Carcinoma
NCT ID: NCT00942331
Key Objective: To determine if patients with advanced transitional cell cancer who are treated with the drugs gemcitabine and cisplatin in combination with bevacizumab, survive longer than those who are treated with gemcitabine, cisplatin, and a placebo.
RTOG-0926: A Phase II Protocol for Patients with Stage T1 Bladder Cancer to Evaluate Selective Bladder Preserving Treatment by Radiation Therapy Concurrent with Radiosensitizing Chemotherapy Following a Thorough Transurethral Surgical Re-Staging
NCT ID: NCT00981656
Key Objective: To determine if selected patients can achieve a complete remission with a bladder-preserving treatment strategy using radiation and chemotherapy.
OSU-11084: Open vs Robotic-Assisted Radical Cystectomy: A Randomized Trial
NCT ID: NCT01157676
Key Objective: To compare how quickly patients recover from open bladder surgery versus robotic-assisted radical bladder surgery with pelvic lymph node dissection.
SWOG-S1011: A Phase III Surgical Trial to Evaluate the Benefit of a Standard versus an Extended Pelvic Lymphadenectomy Performed at time of Radical Cystectomy for Muscle Invasive Urothelial Cancer
NCT ID: NCT01224665
Key Objective: To determine the impact of more extensive lymph node removal for bladder cancer treatment.
ALLIANCE-A021203: Randomized Phase II Study Comparing Cabozantinib with Commercially Supplied Sunitinib in Patients with Previously Untreated, Locally Advanced, or Metastatic Renal Cell Carcinoma
NCT ID: NCT01835158
Key Objective: To determine if patients with renal cancer treated with a new agent, cabozantinib, will survive longer without disease progression compared to those patients who are treated with the drug sunitinib.
OSU-11151: Phase I/II Study of High Dose Interleukin 2, Aldesleukin, in Combination with the Histone Deacetylase Inhibitor Entinostat in Patients with Metastatic Renal Cell Carcinoma
NCT ID: NCT01038778
Key Objective: To evaluate patients with metastatic kidney cancer who are treated with high dose interleukin 2 (aldesleukin) and entinostat. The main outcomes of this trial are the safety and tolerability of this drug combination.
OSU-13120: A Phase 3, Randomized, Controlled Study of Cabozantinib (XL184) vs Everolimus in Subjects with Metastatic Renal Cell Carcinoma that has Progressed after Prior VEGFR Tyrosine Kinase Inhibitor Therapy
NCT ID: NCT01865747
Key Objective: To compare two chemotherapy drugs, cabozantinib and everolimus, for metastatic renal cancer. The major outcomes are safety, toxicity, and impact on cancer. This study is designed for patients who have progressed after one treatment regimen.
Modulation of antitumor immunity by dietary soy and its isoflavone constituents
National Institutes of Health – National Cancer Institute
Investigators: Greg Lesinski, PhD, Steven K. Clinton, MD, PhD; Yael Vodovotz, PhD, Gregory S. Young, MS
Key Objective: Soybeans and the foods derived from them are a rich source of bioactive phytochemicals that promote health. Soy isoflavones are hypothesized to act through various pathways to impact prostate cancer (PCa) progression; however, one area that has received very little focus is the impact of soy components on the immune system. The goals of this study are to investigate the ways dietary soy and its isoflavone constituents modulate signal transduction pathways and immune cell populations relevant to inflammation and prostate cancer.
Regulation of androgen receptor function by H3K4 methylation in prostate cancer
National Institutes of Health – National Cancer Institute
Investigators: Qianben Wang, PhD, Steven K. Clinton, MD, PhD; Shili Lin, PhD; Debra L. Zynger, MD
Key Objectives: The evolution of prostate cancer from an androgen-dependent state (ADPC) to one that is castration-resistant (CRPC) marks the lethal progression of the disease. Understanding the pathogenesis of CRPC and development of novel therapies for CRPC remains an urgent need. The androgen receptor (AR), a ligand-dependent transcription factor, is still expressed and functional in CRPC; however, how AR regulates target genes in CRPC and the functional roles of AR target genes in CRPC is poorly understood. Our goal is to better define these molecular and genetic processes and define new drugs to effectively treat CRPC.
Inhibition of aberrant FoxA1-CREB1 signaling in castration-resistant prostate cancer
Department of Defense
Investigators: Qianben Wang, PhD, Steven K. Clinton, MD, PhD
Key Objectives: Understanding the mechanistic transition from an androgen dependent prostate cancer (ADPC) to the lethal castrate-resistant state (CRPC) is necessary for development of novel therapies. FoxA1, a member of the FoxA subfamily of winged helix/forkhead (Fox) transcription factors, is highly expressed in both ADPC and CRPC and functions as a “pioneer factor” that is critical for cancer cell gene expression. We are testing the hypothesis that aberrant FoxA1/CREB1 regulation induces novel gene expression programs in CRPC, and that targeting FoxA1/CREB1 and their target genes inhibits prostate cancer growth.
Translating novel antitumor targets of vitamin E into new chemopreventive agents
National Institutes of Health – National Cancer Institute
Investigators: Ching-Shih Chen, PhD, Steven K. Clinton, MD, PhD; Samuel K. Kulp, DVM, PhD
Key Objectives: Utilizing the chemical structure of vitamin E, novel compounds have been derived and are being tested for their ability to prevent prostate cancer. A novel class of vitamin E-derived compounds including gamma-VE5 appear to act as targeted inhibitors for prostate cancer prevention and therapy. We will conduct structure-based lead optimization of gamma-VE5 to develop more potent targeted inhibitors, precisely define how they act, and assess the cancer preventive and treatment efficacy in multiple experimental models of prostate carcinogenesis.
Feasibility of an exercise and dietary intervention in men on prolonged ADT
National Institutes of Health – National Cancer Institute
Investigators: Brian Focht, PhD, Steven K. Clinton, MD, PhD
Key Objectives: Androgen-deprivation therapy is the foundation of treatment for men with metastatic prostate cancer (PC) and is now frequently incorporated into multimodality strategies for the curative treatment of locally advanced PC. Unfortunately, the catabolic effects of ADT result in significant morbidity including loss of lean muscle mass, increased fat mass, reduced muscle strength, and lower bone mineral density. In turn, these adverse effects of ADT are linked with functional decline and frailty. It is becoming increasingly clear that PC patients endure long and lingering impacts on physical function, health status, and quality of life (QOL) that accompany ADT as a “trade-off” for more effective cancer control and extended longevity. Lifestyle modification, including change in exercise and dietary behaviors, may offset, or even reverse, the adverse effects that accompany long-term administration of ADT. Our long term research goal is to develop innovative and effective lifestyle interventions for the treatment of PC patients undergoing prolonged ADT. The objective for this current application is to determine the feasibility and preliminary efficacy of an exercise and dietary intervention upon functional, disease, and QOL outcomes in PC patients undergoing ADT.
Prostate cancer outcomes and phytochemical levels in TRAMP mice feed food-based vitamin D and soy.
Ohio Agricultural Research and Development Center
Investigators: Kenneth Riedl, PhD, Steven K. Clinton, MD, PhD; Steven J. Schwartz, PhD; Yael Vodovotz, PhD
Key Objectives: Both vitamin D and the bioactive compounds in soy have been shown to prevent prostate cancer in experimental models. Interestingly, the compounds in soy may inhibit the degredation of the active form of vitamin D. This study is designed to test the hypothesis that a combination of soy and vitamin D, when creatively delivered via a unique vitamin D-enriched soy bread, will have enhanced anti-prostate cancer activity and that the bioactive component in soy impact the metabolism of vitamin D in vivo.
Impact of androgen deprivation therapy on dardiac function in prostate cancer patients
OSU Comprehensive Cancer Center Pelotonia Grant Funding
Investigators: Steven K. Clinton, MD, PhD., Brian Focht, PhD; Subha Raman, MD; Orlando Simmonetti, PhD
Key Objectives: Androgen deprivation therapy (ADT) is frequently used as a component of curative multidisciplinary approaches for men with high-risk localized prostate cancer or as initial therapy in the battle to limit the progression of metastatic disease. Yet, we are just beginning to appreciate some of the consequences of ADT that impact the health and quality of life of men undergoing this treatment. Accumulating research demonstrates a relationship between ADT and decline of physical performance related to: loss of skeletal muscle mass, lower bone mineral density, greater risk of metabolic syndrome, combined with a fatigue syndrome which results in meaningful declines in performance status and quality of life. We aim to quantify changes in cardiac performance in men on ADT using the novel non-magnetic treadmill stress test and cardiac MRI system that has been developed at OSU. The long-term goal of our research program is to determine the optimal dietary and exercise interventions that will prevent deleterious consequences of ADT on cardiovascular health, physical performance and quality of life.
Tangerine tomato phytochemical bioavailability and metabolism in men with prostate cancer
OSU Comprehensive Cancer Center Pelotonia Grant Funding
Investigators: Steven Schwartz, PhD, Steven K. Clinton, MD, PhD
Key Objectives: Epidemiologic and laboratory studies support the hypothesis that diets rich in tomato products may reduce risk of prostate cancer or enhance efficacy of prostate cancer therapy. Tomatoes are a rich source of lycopene (LYC), a carotenoid responsible for their red color, as well as many other bioactive phytochemicals. LYC exists as the trans-isomer in red tomato varieties, but a unique variety of tomato, known as the tangerine tomato, has been bred at OSU for high concentrations of the cis isomer of LYC which may have enhanced bioavailability. The objectives of the proposed study are to compare a red tomato juice to a juice made from tangerine tomatos for patient compliance and safety/toxicity, accumulation of carotenoids in the plasma and prostate tissue, and impact on biomarkers of prostate cancer.
Maximizing the impact of tomatoes for prostate cancer prevention: The impact of tomato variety and carotenoid profiles
American Institute for Cancer Research
Investigators: Steven K. Clinton, MD, PhD, Michael A. Freitas, PhD; Steven J. Schwartz, PhD; Gregory S. Young, MS
Key Objectives: Epidemiologic and laboratory studies support the hypothesis that diets rich in tomato products may reduce risk of prostate cancer or enhance efficacy of prostate cancer therapy. Tomatoes are a rich source of lycopene (LYC), a carotenoid responsible for their red color, as well as many other bioactive phytochemicals. LYC exists as the trans-isomer in red tomato varieties, but a unique variety of tomato, known as the tangerine tomato, has been bred at OSU for high concentrations of the cis isomer of LYC which may have enhanced bioavailability. The objectives of the proposed study are to compare the antiprostate cancer effect of a diet containing red tomatoes to a diet containing tangerine tomatoes in the TRAMP model of prostate cancer and investigate differences in bioavailabity and mechanism of action.