Medicine and Health Sciences Commons^™

Application Of Geographic Information Systems (Gis) In The Study Of Prostate Cancer Disparities: A Systematic Review, Christiane J. El Khoury

Department of Medical Oncology Faculty Papers

Introduction: PCa is one of the cancers that exhibits the widest disparity gaps. Geographical place of residence has been shown to be associated with healthcare access/utilization and PCa outcomes. Geographical Information Systems (GIS) are widely being utilized for PCa disparities research, however, inconsistencies in their application exist. This systematic review will summarize GIS application within PCa disparities research, highlight gaps in the literature, and propose alternative approaches. Methods: This paper followed the methods of the Cochrane Collaboration and the criteria set of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Articles published in peer-reviewed journals were searched through …

Evidence-Based Prostate Cancer Screening Interventions For Black Men: A Systematic Review, Abigail Lopez, Jared T. Bailey, Dorothy Galloway, Leanne Woods-Burnham, Susanne B. Montgomery, Rick Kittles, Dede K. Teteh-Brooks

Health Sciences and Kinesiology Faculty Articles

Abstract

Prostate cancer is the second leading cause of death for men in the U.S. and Black men are twice as likely to die from the disease. However, prostate cancer, if diagnosed at an earlier stage, is curable. The purpose of this review is to identify prostate cancer screening clinical trials that evaluate screening decision-making processes of Black men.

Methods

The databases PubMed, Ovid MEDLINE, CINAHL Plus, and PsychInfo were utilized to examine peer-reviewed publications between 2017 and 2023. Data extracted included implementation plans, outcome measures, intervention details, and results of the study. The Critical Appraisal Skills Programme was used …

Tumor-Associated Antigen Targets For Novel Immune-Based Strategies In Prostate Cancer, Amman Bhasin, Patrick Mille, Aditya Eturi, Andrew Iskander, William Tester, Kevin Zarrabi

Kimmel Cancer Center Faculty Papers

Prostate cancer remains the most common malignancy among men in the United States. Advancements in androgen receptor signaling blockade have led to landmark approvals for its use in patients with locally advanced and metastatic disease. However, additional novel therapeutic strategies for both hormone-sensitive and castration-resistant diseases remain ongoing areas of study. Thus, we turn to the growth of immuno-oncology, which has led to improved treatment outcomes for a variety of hematologic and solid tumor malignancies. Prostate cancers have shown only modest results with immune checkpoint inhibition in published trials, and innovative strategies are now looking into enhancing cytotoxic T-cell activity …

Evaluation Of Ar, Ar-V7, And P160 Family As Biomarkers For Prostate Cancer: Insights Into The Clinical Significance And Disease Progression, Ruan Pimenta, Feres Camargo Malulf, Poliana Romão, Giovana Vilas Boas Caetano, Karina Serafim Da Silva, Vitoria Ghazarian, Gabriel A Dos Santos, Vanessa Guimarães, Iran Amorim Silva, Juliana Alves De Camargo, Saulo Recuero, Bárbara V Lima Aguiar Melão, Alberto Azoubel Antunes, Miguel Srougi, William Nahas, Katia R M Leite, Sabrina T Reis

Faculty and Staff Publications

PURPOSE: To assess the role of the p160 family, AR, and AR-V7 in different initial presentations of prostate cancer and their association with clinical endpoints related to tumor progression.

METHODS: The study sample comprises 155 patients who underwent radical prostatectomy and 11 healthy peripheral zone biopsies as the control group. Gene expression was quantified by qPCR from the tissue specimens. The statistical analysis investigated correlations between gene expression levels, associations with disease presence, and clinicopathological features. Additionally, ROC curves were applied for distinct PCa presentations, and time-to-event analysis was used for clinical endpoints.

RESULTS: The AR-V7 diagnostic performance for any …

27-Hydroxycholesterol And Dna Damage Repair: Implication In Prostate Cancer, Gloria Cecilia Galvan, Nadine Friedrich, Sanjay Das, James Daniels, Sara Pollan, Shweta Dambal, Ryusuke Suzuki, Sergio Sanders, Sungyong You, Hisashi Tanaka, Yeon-Joo Lee, Wei Yuan, Johann De Bono, Irina Vasilevskaya, Karen Knudsen, Michael Freeman, Stephen Freedland

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

INTRODUCTION: We previously reported that cholesterol homeostasis in prostate cancer (PC) is regulated by 27-hydroxycholesterol (27HC) and that CYP27A1, the enzyme that converts cholesterol to 27HC, is frequently lost in PCs. We observed that restoring the CYP27A1/27HC axis inhibited PC growth. In this study, we investigated the mechanism of 27HC-mediated anti-PC effects.

METHODS: We employed in vitro models and human transcriptomics data to investigate 27HC mechanism of action in PC. LNCaP (AR+) and DU145 (AR-) cells were treated with 27HC or vehicle. Transcriptome profiling was performed using the Affymetrix GeneChip™ microarray system. Differential expression was determined, and gene set enrichment …

Intensity Modulated Radiation Therapy With Stereotactic Body Radiation Therapy Boost For Unfavorable Prostate Cancer: Five-Year Outcomes, Michael Carrasquilla, Tamir Sholklapper, Abigail Pepin, Nicole Hodgins, Siyuan Lei, Abdul Rashid, Malika Danner, Alan Zwart, Grecia Bolanos, Marilyn Ayoob, Thomas Yung, Nima Aghdam, Brian Collins, Simeng Suy, Deepak Kumar, Ryan Hankins, Keith Kowalczyk, Nancy Dawson, Sean Collins

Einstein Health Papers

PURPOSE: Intensity-modulated radiation therapy (IMRT) with brachytherapy boost for unfavorable prostate cancer has been shown to improve biochemical relapse-free survival compared to IMRT alone. Stereotactic body radiation therapy (SBRT) is a less-invasive alternative to brachytherapy. Early outcomes utilizing SBRT boost suggest low rates of high-grade toxicity with a maintained patient-reported quality of life. Here, we report the 5-year progression-free survival (PFS) and prostate cancer-specific survival (PCSS) of patients treated with IMRT plus SBRT boost.

MATERIALS AND METHODS: Between 2008 and 2020, 255 patients with unfavorable prostate cancer were treated with robotic SBRT (19.5 Gy in three fractions) followed by fiducial-guided …

Pca-Clf: A Classifier Of Prostate Cancer Patients Into Patients With Indolent And Aggressive Tumors Using Machine Learning, Yashwanth Karthik Kumar Mamidi, Tarun Karthik Kumar Mamidi, Md Wasi Ul Kabir, Jiande Wu, Md Tamjidul Hoque, Chindo Hicks

School of Medicine Faculty Publications

A critical unmet medical need in prostate cancer (PCa) clinical management centers around distinguishing indolent from aggressive tumors. Traditionally, Gleason grading has been utilized for this purpose. However, tumor classification using Gleason Grade 7 is often ambiguous, as the clinical behavior of these tumors follows a variable clinical course. This study aimed to investigate the application of machine learning techniques (ML) to classify patients into indolent and aggressive PCas. We used gene expression data from The Cancer Genome Atlas and compared gene expression levels between indolent and aggressive tumors to identify features for developing and validating a range of ML …

Evidence Of Novel Susceptibility Variants For Prostate Cancer And A Multiancestry Polygenic Risk Score Associated With Aggressive Disease In Men Of African Ancestry., Fei Chen, Ravi K Madduri, Alex A Rodriguez, Burcu F Darst, Alisha Chou, Xin Sheng, Anqi Wang, Jiayi Shen, Edward J Saunders, Suhn K Rhie, Jeannette T Bensen, Sue A Ingles, Rick A Kittles, Sara S Strom, Benjamin A Rybicki, Barbara Nemesure, William B Isaacs, Janet L Stanford, Wei Zheng, Maureen Sanderson, Esther M John, Jong Y Park, Jianfeng Xu, Ying Wang, Sonja I Berndt, Chad D Huff, Edward D Yeboah, Yao Tettey, Joseph Lachance, Wei Tang, Christopher T Rentsch, Kelly Cho, Benjamin H Mcmahon, Richard B Biritwum, Andrew A Adjei, Evelyn Tay, Ann Truelove, Shelley Niwa, Thomas A Sellers, Kosj Yamoah, Adam B Murphy, Dana C Crawford, Alpa V Patel, William S Bush, Melinda C Aldrich, Olivier Cussenot, Gyorgy Petrovics, Jennifer Cullen, Christine M Neslund-Dudas, Mariana C Stern, Zsofia Kote-Jarai, Koveela Govindasami, Michael B Cook, Anand P Chokkalingam, Ann W Hsing, Phyllis J Goodman, Thomas J Hoffmann, Bettina F Drake, Jennifer J Hu, Jacob M Keaton, Jacklyn N Hellwege, Peter E Clark, Mohamed Jalloh, Serigne M Gueye, Lamine Niang, Olufemi Ogunbiyi, Michael O Idowu, Olufemi Popoola, Akindele O Adebiyi, Oseremen I Aisuodionoe-Shadrach, Hafees O Ajibola, Mustapha A Jamda, Olabode P Oluwole, Maxwell Nwegbu, Ben Adusei, Sunny Mante, Afua Darkwa-Abrahams, James E Mensah, Halimatou Diop, Stephen K Van Den Eeden, Pascal Blanchet, Jay H Fowke, Graham Casey, Anselm J Hennis, Alexander Lubwama, Ian M Thompson, Robin Leach, Douglas F Easton, Michael H Preuss, Ruth J Loos, Susan M Gundell, Peggy Wan, James L Mohler, Elizabeth T Fontham, Gary J Smith, Jack A Taylor, Shiv Srivastava, Rosaline A Eeles, John D Carpten, Adam S Kibel, Luc Multigner, Marie-Élise Parent, Florence Menegaux, Geraldine Cancel-Tassin, Eric A Klein, Caroline Andrews, Timothy R Rebbeck, Laurent Brureau, Stefan Ambs, Todd L Edwards, Stephen Watya, Stephen J Chanock, John S Witte, William J Blot, J Michael Gaziano, Amy C Justice, David V Conti, Christopher A Haiman

Student and Faculty Publications

BACKGROUND: Genetic factors play an important role in prostate cancer (PCa) susceptibility.

OBJECTIVE: To discover common genetic variants contributing to the risk of PCa in men of African ancestry.

DESIGN, SETTING, AND PARTICIPANTS: We conducted a meta-analysis of ten genome-wide association studies consisting of 19378 cases and 61620 controls of African ancestry.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Common genotyped and imputed variants were tested for their association with PCa risk. Novel susceptibility loci were identified and incorporated into a multiancestry polygenic risk score (PRS). The PRS was evaluated for associations with PCa risk and disease aggressiveness.

RESULTS AND LIMITATIONS: Nine …

Cancer Cell-Extrinsic Roles For The Androgen Receptor In Prostate Cancer, Andrew W Hahn, Bilal A Siddiqui, Javier Leo, Eleonora Dondossola, Kaitlin J Basham, Cindy K Miranti, Daniel E Frigo

Student and Faculty Publications

Given the central role of the androgen receptor (AR) in prostate cancer cell biology, AR-targeted therapies have been the backbone of prostate cancer treatment for over 50 years. New data indicate that AR is expressed in additional cell types within the tumor microenvironment. Moreover, targeting AR for the treatment of prostate cancer has established side effects such as bone complications and an increased risk of developing cardiometabolic disease, indicating broader roles for AR. With the advent of novel technologies, such as single-cell approaches and advances in preclinical modeling, AR has been identified to have clinically significant functions in other cell …

Interactions Of Snps In Folate Metabolism Related Genes On Prostate Cancer Aggressiveness In European Americans And African Americans, Hui Yi Lin, Susan E. Steck, Indrani Sarkar, Elizabeth T.H. Fontham, Alan Diekman, Lora J. Rogers, Calvin T. Ratliff, Jeannette T. Bensen, James L. Mohler, L. Joseph Su

School of Public Health Faculty Publications

Background: Studies showed that folate and related single nucleotide polymorphisms (SNPs) could predict prostate cancer (PCa) risk. However, little is known about the interactions of folate-related SNPs associated with PCa aggressiveness. The study’s objective is to evaluate SNP–SNP interactions among the DHFR 19-bp polymorphism and 10 SNPs in folate metabolism and the one-carbon metabolism pathway associated with PCa aggressiveness. Methods: We evaluated 1294 PCa patients, including 690 European Americans (EAs) and 604 African Americans (AAs). Both individual SNP effects and pairwise SNP–SNP interactions were analyzed. Results: None of the 11 individual polymorphisms were significant for EAs and AAs. Three SNP–SNP …

Prostate Cancer Aggressiveness And Financial Toxicity Among Prostate Cancer Patients, K. C. Madhav, Evrim Oral, Ariane L. Rung, Edward Trapido, Laura S. Rozek, Elizabeth T.H. Fontham, Jeannette T. Bensen, Laura Farnan, Susan E. Steck, Lixin Song, James L. Mohler, Saira Khan, Sanah Vohra, Edward S. Peters

School of Public Health Faculty Publications

Introduction: Financial toxicity (FT) is a growing concern among cancer survivors that adversely affects the quality of life and survival. Individuals diagnosed with aggressive cancers are often at a greater risk of experiencing FT. The objectives of this study were to estimate FT among prostate cancer (PCa) survivors after 10−15 years of diagnosis, assess the relationship between PCa aggressiveness at diagnosis and FT, and examine whether current cancer treatment status mediates the relationship between PCa aggressiveness and FT. Methods: PCa patients enrolled in the North Carolina-Louisiana Prostate Cancer Project (PCaP) were recontacted for long-term follow-up. The prevalence of FT in …

Social Ecological Influences On Treatment Decision-Making In Men Diagnosed With Low Risk, Localised Prostate Cancer, Megan Mcintosh, Melissa J. Opozda, Camille E. Short, Daniel A. Galvão, Rebecca Tutino, Michael Diefenbach, Behfar Ehdaie, Christian Nelson

Research outputs 2022 to 2026

Objective: Individuals diagnosed with low risk, localised prostate cancer (PCa) face a difficult decision between active surveillance (AS) and definitive treatment. We aimed to explore perceived influences on treatment decision-making from the patient and partner's perspectives. Methods: Patients (and partners) who met AS criteria and had chosen their treatment were recruited. Semi-structured individual interviews were conducted via telephone to explore experiences of diagnosis, impact on patient lifestyle, experiences with physicians, treatment preferences/choice, treatment information understanding and needs, and overall decision-making process. Interviews were audio recorded, transcribed verbatim, and analysed using Reflexive Thematic Analysis. Results: Twenty-four male patients (18 chose AS) …

To Bind Or Not To Bind: Cistromic Reprogramming In Prostate Cancer, Michelle Shen, Léa-Kristine Demers, Swneke D Bailey, David P Labbé

Student and Faculty Publications

The term "cistrome" refers to the genome-wide location of regulatory elements associated with transcription factor binding-sites. The cistrome of key regulatory factors in prostate cancer etiology are substantially reprogrammed and altered during prostatic transformation and disease progression. For instance, the cistrome of the androgen receptor (AR), a ligand-inducible transcription factor central in normal prostate epithelium biology, is directly impacted and substantially reprogrammed during malignant transformation. Accumulating evidence demonstrates that additional transcription factors that are frequently mutated, or aberrantly expressed in prostate cancer, such as the pioneer transcription factors Forkhead Box A1 (FOXA1), the homeobox protein HOXB13, and the GATA binding …

Dose-Intensified Stereotactic Ablative Radiation For Localized Prostate Cancer, Lily Chen, Bhavani S. Gannavarapu, University Of Texas Southwestern Medical Center At Dallas, Michael R. Folkert, Michael Dohopolski, Ang Gao, Chul Ahn, Jeffrey Cadeddu, Aditya Bagrodia

School of Medicine Publications and Presentations

Purpose: Stereotactic ablative radiation (SAbR) has been increasingly used in prostate cancer (PCa) given its convenience and cost efficacy. Optimal doses remain poorly defined with limited prospective comparative trials and long-term safety/efficacy data at higher dose levels. We analyzed toxicity and outcomes for SAbR in men with localized PCa at escalated 45 Gy in 5 fractions.

Methods and Materials: This study retrospectively analyzed men from 2015 to 2019 with PCa who received linear-accelerator-based SAbR to 45 Gy in 5 fractions, along with perirectal hydrogel spacer, fiducial placement, and MRI-based planning. Disease control outcomes were calculated from end of treatment. Minimally …

Myokine Expression And Tumor-Suppressive Effect Of Serum Following 12 Weeks Of Exercise In Prostate Cancer Patients On Adt, Jin-Soo Kim, Rebekah Louise Wilson, Dennis Taaffe, Daniel A. Galvao, Elin S. Gray, Robert Newton

Research outputs 2014 to 2021

Purpose:

Although several mechanisms have been proposed for the tumor-suppressive effect of exercise, little attention has been given to myokines, even though skeletal muscle is heavily recruited during exercise resulting in myokine surges. We measured resting serum myokine levels before and after an exercise-based intervention and the effect of this serum on prostate cancer cell growth.

Methods:

Ten prostate cancer patients undertaking androgen deprivation therapy (age, 73.3 ± 5.6 yr) undertook a 12-wk exercise-based intervention including supervised resistance training, self-directed aerobic exercise, and protein supplementation. Body composition was assessed by dual-energy x-ray absorptiometry and muscle strength by the one-repetition maximum …

Associations Of Fat And Muscle Mass With Overall Survival In Men With Prostate Cancer: A Systematic Review With Meta-Analysis, Pedro Lopez, Robert U. Newton, Dennis R. Taaffe, Favil Singh, Laurien M. Buffart, Nigel Spry, Colin Tang, Fred Saad, Daniel A. Galvao

Research outputs 2014 to 2021

Background

To systematically review and analyse the associations between fat and muscle mass measures with overall survival in men with prostate cancer.

Methods

A systematic search was conducted in CINAHL, Cochrane Library, EMBASE, PubMed, and Web of Science databases from inception to December 2020, while abstracts from the American Society of Clinical Oncology (ASCO), Clinical Oncology Society of Australia (COSA), and the American College of Sports Medicine (ACSM) conferences were searched from 2014 to 2020. Eligible articles examined the association of body composition measures, such as fat mass (e.g., fat mass, visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and …

Exercise In Preventing Falls For Men With Prostate Cancer: A Modelled Cost-Utility Analysis, Kim Edmunds, Paul Scuffham, Robert U. Newton, Daniel A. Galvão, Haitham Tuffaha

Research outputs 2022 to 2026

Introduction:

Men who receive androgen deprivation therapy (ADT) for prostate cancer (PCa) are a vulnerable falls population due to the side effects of treatment. The purpose of this paper is to determine the cost-effectiveness of exercise in preventing falls and fractures for this high-risk population in Australia.

Methods:

A decision analytic model was constructed to evaluate the cost utility of an exercise intervention compared to usual care from a health system perspective. The intervention comprised two 1-h sessions of supervised exercise per week over 1 year for men with non-metastatic PCa receiving curative radiation therapy and ADT. A Markov model …

Exercise In Advanced Prostate Cancer Elevates Myokine Levels And Suppresses In-Vitro Cell Growth, Jin Soo Kim, Dennis R. Taaffe, Daniel A. Galvão, Nicolas H. Hart, Elin Gray, Charles J. Ryan, Stacey A. Kenfield, Fred Saad, Robert U. Newton

Research outputs 2022 to 2026

Background:

Altering the systemic milieu through exercise has been proposed as a potential mechanism underlying exercise-driven tumour suppression. It is not yet known whether men with advanced prostate cancer can elicit such adaptations following a program of exercise. The purpose is to examine myokine levels of serum acquired from metastatic castrate-resistant prostate cancer (mCRPC) patients recruited to the INTERVAL-GAP4 trial before and after 6 months of exercise and its tumour-suppressive effect.

Methods:

Twenty-five men with mCRPC (age = 74.7 ± 7.1 yrs) were randomised to supervised multimodal (aerobic and resistance) exercise (EX) or self-directed exercise control group (CON). Body composition …

Effects Of Exercise During Radiotherapy On Physical Function And Treatment-Related Side Effects In Men With Prostate Cancer: A Systematic Review And Meta-Analysis, Oliver Schumacher, Hao Luo, Dennis Taaffe, Daniel A. Galvao, Colin Tang, Raphael Chee, Nigel Spry, Robert Newton

Research outputs 2014 to 2021

Purpose

Radiation therapy is a commonly used treatment for prostate cancer; however, the side effects may negatively affect quality of life and cause patients to be less physically active. Although exercise has been shown to mitigate radiation therapy–related fatigue in men with prostate cancer during radiation therapy, other adverse effects of treatment such as physical deconditioning, urinary symptoms, or sexual dysfunction have not been systematically reviewed in this patient population. Thus, the purpose of this review was to investigate the effect of exercise on physical function and treatment-related side effects in men with prostate cancer undergoing radiation therapy.

Methods

A …

Potential Role Of Exercise Induced Extracellular Vesicles In Prostate Cancer Suppression, Ying Zhang, Jin-Soo Kim, Tain-Zhen Wang, Robert U. Newton, Daniel A. Galvao, Robert A. Gardiner, Michelle M. Hill, Dennis Taaffe

Research outputs 2014 to 2021

Physical exercise is increasingly recognized as a valuable treatment strategy in managing prostate cancer, not only enhancing supportive care but potentially influencing disease outcomes. However, there are limited studies investigating mechanisms of the tumor-suppressive effect of exercise. Recently, extracellular vesicles (EVs) have been recognized as a therapeutic target for cancer as tumor-derived EVs have the potential to promote metastatic capacity by transferring oncogenic proteins, integrins, and microRNAs to other cells and EVs are also involved in developing drug resistance. Skeletal muscle has been identified as an endocrine organ, releasing EVs into the circulation, and levels of EV-containing factors have been …

The Tumor Suppressor Mir-642a-5p Targets Wilms Tumor 1 Gene And Cell-Cycle Progression In Prostate Cancer, Dianne J. Beveridge, Kirsty L. Richardson, Michael R. Epis, Rikki A. M. Brown, Lisa M. Stuart, Andrew J. Woo, Peter J. Leedman

Research outputs 2014 to 2021

RNA-based therapeutics are emerging as innovative options for cancer treatment, with microRNAs being attractive targets for therapy development. We previously implicated microRNA-642a-5p (miR-642a-5p) as a tumor suppressor in prostate cancer (PCa), and here we characterize its mode of action, using 22Rv1 PCa cells. In an in vivo xenograft tumor model, miR-642a-5p induced a significant decrease in tumor growth, compared to negative control. Using RNA-Sequencing, we identified gene targets of miR-642a-5p which were enriched for gene sets controlling cell cycle; downregulated genes included Wilms Tumor 1 gene (WT1), NUAK1, RASSF3 and SKP2; and upregulated genes included IGFBP3 and GPS2. Analysis of …

Psychological Distress In Men With Prostate Cancer Undertaking Androgen Deprivation Therapy: Modifying Effects Of Exercise From A Year-Long Randomized Controlled Trial, Daniel A. Galvão, Robert U. Newton, Suzanne K. Chambers, Nigel Spry, David Joseph, Robert A. Gardiner, Ciaran M. Fairman, Dennis R. Taaffe

Research outputs 2014 to 2021

© 2021, The Author(s). Objectives: To assess the long-term effects of various exercise modes on psychological distress in men with prostate cancer on androgen deprivation therapy (ADT). Patients and methods: 135 prostate cancer patients aged 43–90 years on ADT were randomized to twice weekly supervised impact loading and resistance exercise (ImpRes), supervised aerobic and resistance exercise (AerRes), and usual care/delayed supervised aerobic exercise (DelAer) for 12 months, and completed measures of psychological distress using the Brief Symptom Inventory-18 (BSI-18). BSI-18 provides three subscales for anxiety, depression, and somatisation, as well as the global severity index (GSI) where higher scores indicate …

Association Of Genetic Variants With Prostate Cancer In Africa: A Concise Review, Emmanuel Acheampong, Evans A. Adu, Christian Obirikorang, George Amoah, Osei O. Afriyie, Joseph Yorke, Enoch O. Anto, Michael A. Gyamfi, Emmanuella N. Acheampong, Christian K. Gyasi-Sarpong, Francis A. Yeboah

Research outputs 2014 to 2021

Background: Prostate cancer (PCa) has one of the highest heritability of all major cancers, where the genetic contribution has been documented, and knowledge about the molecular genetics of the disease is increasing. However, the extent and aspects to which genetic variants explain PCa heritability in Africa are limited. Main body: In this review, we summarize studies that highlight how identified genetic variants explain differences in PCa incidence and presentation across ethnic groups. We also present the knowledge gaps in PCa genetics in Africa and why Africa represents an untapped potential ground for genetic studies on PCa. A significant number of …

Effect Of Exercise Adjunct To Radiation And Androgen Deprivation Therapy On Patient-Reported Treatment Toxicity In Men With Prostate Cancer: A Secondary Analysis Of 2 Randomized Controlled Trials, Oliver Schumacher, Daniel A. Galvão, Dennis R. Taaffe, Nigel Spry, David Joseph, Colin Tang, Raphael Chee, Robert U. Newton

Research outputs 2014 to 2021

Purpose: Physical inactivity, in addition to clinical factors, has been associated with higher levels of late pelvic symptoms in patients with prostate cancer (PCa) after radiation therapy. The aim of this study was to investigate the effect of a structured multicomponent exercise program comprised of aerobic and resistance training as well as impact loading on the prevalence and severity of symptoms commonly resulting from androgen deprivation therapy (ADT) and pelvic radiation therapy. Methods and Materials: We performed a secondary analysis of pooled data from 2 randomized controlled trials that investigated the role of exercise on treatment-related side effects in patients …

What Is The Minimal Dose For Resistance Exercise Effectiveness In Prostate Cancer Patients? Systematic Review And Meta-Analysis On Patient-Reported Outcomes, Pedro Lopez, Dennis R. Taaffe, Robert U. Newton, Laurien M. Buffart, Daniel A. Galvão

Research outputs 2014 to 2021

© 2020, The Author(s). Background: Active treatments for prostate cancer are well known to result in several adverse effects such as fatigue, depression and anxiety symptoms, impacting the overall quality of life (QoL) and wellbeing of a considerable proportion of patients. Resistance-based exercise interventions have shown positive effects to reduce or mitigate these treatment-related side effects. However, the minimal dosage required to derive these benefits is unknown. We systematically reviewed the resistance training effects in prostate cancer patients to determine the minimal dosage regarding the exercise components (mode, duration, volume and intensity) on fatigue, QoL, depression and anxiety. Methods: Using …

Using Exercise And Nutrition To Alter Fat And Lean Mass In Men With Prostate Cancer Receiving Androgen Deprivation Therapy: A Narrative Review, Rebekah L. Wilson, Dennis R. Taaffe, Robert U. Newton, Nicolas H. Hart, Philippa Lyons-Wall, Daniel A. Galvao

Research outputs 2014 to 2021

Fat mass (FM) gain and lean mass (LM) loss are common side effects for patients with prostate cancer receiving androgen deprivation therapy (ADT). Excess FM has been associated with an increased risk of developing obesity-related comorbidities, exacerbating prostate cancer progression, and all-cause and cancer-specific mortality. LM is the predominant contributor to resting metabolic rate, with any loss impacting long-term weight management as well as physical function. Therefore, reducing FM and preserving LM may improve patient-reported outcomes, risk of disease progression, and ameliorate comorbidity development. In ADT-treated patients, exercise and nutrition programs can lead to improvements in quality of life and …

Epigenetic Regulation Of Prostate Cancer, Ruixin Wang, Xiaoqi Liu

Toxicology and Cancer Biology Faculty Publications

Prostate cancer is (PCa) the second leading cause of cancer death in males in the United State, with 174,650 new cases and 31,620 deaths estimated in 2019. It has been documented that epigenetic deregulation such as histone modification and DNA methylation contributes to PCa initiation and progression. EZH2 (enhancer of zeste homolog 2), the catalytic subunit of the Polycomb Repressive Complex (PRC2) responsible for H3K27me3 and gene repression, has been identified as a promising target in PCa. In addition, overexpression of other epigenetic regulators such as DNA methyltransferases (DNMT) is also observed in PCa. These epigenetic regulators undergo extensive post-translational …

Time On Androgen Deprivation Therapy And Adaptations To Exercise: Secondary Analysis From A 12-Month Randomized Controlled Trial In Men With Prostate Cancer, Dennis R. Taaffe, Laurien M. Buffart, Robert U. Newton, Nigel Spry, James Denham, David Joseph, David Lamb, Suzanne K. Chambers, Daniel A. Galvao

Research outputs 2014 to 2021

Objectives

To explore if duration of previous exposure to androgen deprivation therapy (ADT) in men with prostate cancer (PCa) undertaking a year-long exercise programme moderates the exercise response with regard to body composition and muscle performance, and also to explore the moderator effects of baseline testosterone, time since ADT, and baseline value of the outcome.

Patients and Methods

In a multicentre randomized controlled trial, 100 men who had previously undergone either 6 months (short-term) or 18 months (long-term) of ADT in combination with radiotherapy, as part of the TROG 03.04 RADAR trial, were randomized to 6 months supervised exercise, followed …

Exercise Preserves Physical Function In Prostate Cancer Patients With Bone Metastases, Daniel A. Galvao, Dennis R. Taaffe, Nigel Spry, Prue Cormie, David Joseph, Suzanne K. Chambers, Raphael Chee, Carolyn J. Peddle-Mcintyre, Nicolas H. Hart, Freerk T. Baumann, James Denham, Michael Baker, Robert U. Newton

Research outputs 2014 to 2021

The presence of bone metastases has excluded participation of cancer patients in exercise interventions and is a relative contraindication to supervised exercise in the community setting due to concerns of fragility fracture. We examined the efficacy and safety of a modular multi-modal exercise program in prostate cancer patients with bone metastases.Between 2012 and 2015, 57 prostate cancer patients (70.0 ± 8.4 years; BMI 28.7 ± 4.0 kg/m) with bone metastases (pelvis 75.4%, femur 40.4%, rib/thoracic spine 66.7%, lumbar spine 43.9%, humerus 24.6%, other sites 70.2%) were randomised to multi-modal supervised aerobic, resistance and flexibility exercises undertaken thrice weekly (EX, n …

Loss Of Exogenous Androgen Dependence By Prostate Tumor Cells Is Associated With Elevated Glucuronidation Potential, Brenna M. Zimmer, Michelle E. Howell, Qin Wei, Linlin Ma, Trevor Romsdahl, Eileen G. Loughman, Jennifer E. Markham, Javier Seravalli, Joseph J. Barycki, Melanie A. Simpson

Department of Biochemistry: Faculty Publications

Prostate epithelial cells control the potency and availability of androgen hormones in part by inactivation and elimination. UDP-glucose dehydrogenase (UGDH) catalyzes the NAD⁺-dependent oxidation of UDP-glucose to UDP-glucuronate, an essential precursor for androgen inactivation by the prostate glucuronidation enzymes UGT2B15 and UGT2B17. UGDH expression is androgen stimulated, which increases the production of UDP-glucuronate, and fuels UGT-catalyzed glucuronidation. In this study, we compared the glucuronidation potential and its impact on androgen-mediated gene expression in an isogenic LNCaP model for androgen dependent versus castration resistant prostate cancer. Despite significantly lower androgen-glucuronide output, LNCaP 81 castration resistant tumor cells expressed higher …