Medicine and Health Sciences Commons^™

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 …

The Impact Of Prostate Cancer Treatment On Quality Of Life: A Narrative Review With A Focus On Randomized Data., James M Taylor, Victor E. Chen, Ryan C. Miller, Benjamin A. Greenberger

Department of Radiation Oncology Faculty Papers

Despite excellent oncologic outcomes, the management of localized prostate cancer remains complex and is dependent on multiple factors, including patient life expectancy, medical comorbidities, tumor characteristics, and genetic risk factors. Decades of iterative clinical trials have improved the optimization and utilization of surgical and radiation-based modalities, as well as their combinatorial use with anti-androgen and systemic therapies. While cure rates are high and converging on equivalent disease control should an upfront surgical or radiotherapeutic approach be optimized, the long-term side effects of surgical and radiation-based treatments can differ significantly in nature. Decisions regarding the selection of therapy are therefore best …

Cancer Detection In Radical Prostatectomy Histology Using Convolutional Neural Networks, Laurie Huang

Electronic Thesis and Dissertation Repository

Radical prostatectomy (RP) is a common treatment for prostate cancer. We used RP whole-mount tissue samples from 68 patients stained with haematoxylin and eosin to create cancer maps using four pretrained networks: AlexNet, NASNet, VGG16 and Xception, to classify regions of interest (ROIs) as cancer or non-cancer. Models were trained on either raw images or as tissue component maps (TCMs) containing nuclei, lumina and stroma/other components generated from a trained U-Net.

All models performed similarly; however, VGG16 trained on raw images performed with the highest area under the receiver operating characteristic curve (AUC) of 0.994 (95% confidence interval 0.992-0.996). Ensemble …

Histone Demethylase Phf8 Drives Neuroendocrine Prostate Cancer Progression By Epigenetically Upregulating Foxa2., Qiuli Liu, Jian Pang, Lin-Ang Wang, Zhuowei Huang, Jing Xu, Xingxia Yang, Qiubo Xie, Yiqiang Huang, Tang Tang, Dali Tong, Gaolei Liu, Luofu Wang, Dianzheng Zhang, Qiang Ma, Hualiang Xiao, Weihua Lan, Jun Qin, Jun Jiang

PCOM Scholarly Papers

Neuroendocrine prostate cancer (NEPC) is a more aggressive subtype of castration-resistant prostate cancer (CRPC). Although it is well established that PHF8 can enhance prostate cancer cell proliferation, whether PHF8 is involved in prostate cancer initiation and progression is relatively unclear. By comparing the transgenic adenocarcinoma of the mouse prostate (TRAMP) mice with or without Phf8 knockout, we systemically examined the role of PHF8 in prostate cancer development. We found that PHF8 plays a minimum role in initiation and progression of adenocarcinoma. However, PHF8 is essential for NEPC because not only is PHF8 highly expressed in NEPC but also animals without …

Knowledge And Practice Regarding Prostate Cancer Germline Testing Among Urologists: Gaps To Address For Optimal Implementation, Stacy Loeb, Nataliya Byrne, Dawn Walter, Danil V Makarov, David R Wise, Daniel Becker, Veda N Giri

Department of Medical Oncology Faculty Papers

BACKGROUND: Germline testing is recommended for all men with metastatic prostate cancer (PCa), and for some with localized PCa meeting specific histologic or family history criteria. Germline genetic evaluation has important implications for PCa prognosis and management, as well as implications for family members and cancer screening. Despite the importance of germline evaluation, its utilization in urologic practice is unknown.

MATERIALS AND METHODS: We conducted a 32-item survey of U.S. urologists to examine knowledge of germline testing guidelines and practice patterns. It was shared through email to 6 American Urological Association sections, the Veterans Affairs Urology Mailgroup, and social media. …

Personalized Medicine: The Use Of Biomarkers And Molecularly Targeted Therapies For Patient Care And Cancer Intervention, Wafa Asad, Emily Schmitt Lavin

Mako: NSU Undergraduate Student Journal

Personalized medicine and targeted therapy have been emerging fields of study for the remediation and inhibition of cancer. Personalized medicine in the treatment of cancer involves using genetic, immune, and proteomic profiling to provide therapeutic options as well as prognostic background for every patient and their tumor’s genetic mutations. Targeted therapies allow researchers and medical personnel alike to determine the appropriate treatment for a patient based on the molecular basis and mechanistic actions of a cancerous tumor. The overall significance of this study was to express how these treatments use biomarkers to pinpoint the location, and severity of the cancer, …

The Impact Of Ethnicity And Immigration On Prostate Cancer Mortality In Canada, Noah Stern

Electronic Thesis and Dissertation Repository

Despite the prevalence of prostate cancer its pathogenesis remains unclear. Marked differences in mortality rates have been observed between countries, however, it is unclear whether the source of the observed differences is driven by underlying genetics, geographic, or social factors. This thesis investigated the impact of ethnicity and immigration on prostate cancer mortality in Canada using the Canadian Census Health and Environment Cohort. South Asian and East Asian men were seen to be at decreased risk of prostate cancer mortality, while no increased risk was observed in black men. These results affirm studies showing lower risks in Asian men; however, …

A Comparison Between Rectal Dose In Prostate Radiotherapy Patients Treated With Spaceoar Hydrogel Present Versus Patients Treated Without Spaceoar Hydrogel., David Desano

Culminating Experience Projects

Introduction: External beam radiation therapy is a common treatment option for prostate cancer patients with localized disease. Radiation-induced side effects associated with the rectum can impact a patient’s ability to complete treatment or affect the quality of life years after radiation treatment. Spaceoar hydrogel has been developed to reduce radiation dose to nearby pelvis structures, and therefore decreasing potential side effects.

Methods: A total of 20 patients who received definitive radiation therapy to the prostate and seminal vesicles were selected and placed into 2 groups (10 spaceoar, 10 non-spaceoar). The individuals’ age ranged from 60 to 79 years old with …

Trends In Cancer Prevalence In Punjab, Pakistan: A Systematic Study From 2010 To 2016, Sana Hafeez, Asmat Mahmood, Rizwan Ullah Khan, Naila Malkani

Journal of Bioresource Management

Cancer is the second leading cause of death globally. However, in Pakistan, in the absence of a national cancer registry, it is difficult to predict the current status of cancer incidence. Therefore, a need was felt to design a study that can give a depiction of the prevalence of common cancer types and their relevance to the local population in the absence of a proper cancer registry system. In view of this, data was collected from 2010 to 2016 for breast, prostate, head and neck, cervical and colorectal cancer from the cancer hospitals and centres located all over Punjab, Pakistan. …

Mechanistic And Translational Studies On Skeletal Malignancies, Jeremy Mcguire

USF Tampa Graduate Theses and Dissertations

New treatment strategies are desperately needed for treating skeletal malignancy. Skeletal malignancies can be either primary cancer that originated in the bone, such as osteosarcoma, or metastatic cancer that spread from another organ to the skeleton, as in the case of breast or prostate cancer. In this thesis, I will detail two projects that focus on the discovery of new treatment strategies for both primary skeletal malignancy and metastatic skeletal malignancy.

The first project focuses on the primary skeletal malignancy, osteosarcoma, a rare cancer that is commonly diagnosed in children and young adults and metastasizes to the lungs. The survival …

Smart Delivery Of Genes And Drugs For Treatment Of Cancer, Feng Lin

Theses & Dissertations

The ineffective delivery of genes and drugs have become a big obstacle for the treatment of cancer, due to either poor stability or low aqueous solubility. In the first part, A ROS responsive polymer named poly(ethylene glycol)–poly[aspartamidoethyl(p-boronobenzyl)diethylammonium bromide] (PEG-B-PAEBEA) was developed for codelivery miR-34a mimic and small molecule PLK1 inhibitor volasertib (BI6727) for the treatment of pancreatic ductal adenocarcinoma (PDAC), since tumor suppressor microRNA-34a (miR-34a), which targets many oncogenes related to proliferation, apoptosis, and invasion is significant downregulated while Polo-like kinase 1 (PLK1) closely associated with short survival rates of pancreatic cancer patients is remarkably upregulated . In part 2, …

Machine Learning For Prostate Histopathology Assessment, Wenchao Han

Electronic Thesis and Dissertation Repository

Pathology reporting on radical prostatectomy (RP) specimens is essential to post-surgery patient care. However, current pathology interpretation of RP sections is typically qualitative and subject to intra- and inter-observer variability, which challenges quantitative and repeatable reporting of lesion grade, size, location, and spread. Therefore, we developed and validated a software platform that can automatically detect and grade cancerous regions on whole slide images (WSIs) of whole-mount RP sections to support quantitative and visual reporting. Our study used hæmatoxylin- and eosin-stained WSIs from 299 whole-mount RP sections from 71 patients, comprising 1.2 million 480μm×480μm regions-of-interest (ROIs) covering benign and cancerous tissues …

Using Medical Claims Database To Develop A Population Disease Progression Model For Leuprorelin-Treated Subjects With Hormone-Sensitive Prostate Cancer, Yixuan Zou, Fei Tang, Jeffery C. Talbert, Chee M. Ng

Pharmacy Practice and Science Faculty Publications

Androgen deprivation therapy (ADT) is a widely used treatment for patients with hormone-sensitive prostate cancer (PCa). However, duration of treatment response varies, and most patients eventually experience disease progression despite treatment. Leuprorelin is a luteinizing hormone-releasing hormone (LHRH) agonist, a commonly used form of ADT. Prostate-specific antigen (PSA) is a biomarker for monitoring disease progression and predicting treatment response and survival in PCa. However, time-dependent profile of tumor regression and growth in patients with hormone-sensitive PCa on ADT has never been fully characterized. In this analysis, nationwide medical claims database provided by Humana from 2007 to 2011 was used to …

Prostate Field Cancerization And Exosomes: Association Between Cd9, Early Growth Response 1 And Fatty Acid Synthase, Farideh Amirrad, Philip A. Pytak, Neda Sadeghiani-Pelar, Julie P. T. Nguyen, Emily L. Cauble, Anna C. Jones

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Intracapsular and well‑defined adenocarcinomas of the prostate are often surrounded by tissue areas that harbor molecular aberrations, including those of genetic, epigenetic and biochemical nature. This is known as field cancerization, or a field effect and denotes a state of pre‑malignancy. Such alterations in histologically normal tumor‑adjacent prostatic tissues have been recognized as clinically important and are potentially exploitable as biomarkers of disease and/or targets for preventative/therapeutic intervention. The authors have previously identified and validated two protein markers of field cancerization: The expressional upregulation of the transcription factor early growth response 1 (EGR‑1) and the lipogenic enzyme fatty acid synthase …

The Nuclear Legacy In Appalachia, Michele Morrone, Harold Perkins

Journal of Appalachian Health

Nestled in the rolling hills of Appalachia Ohio is a reminder of the role that the region played in winning the Cold War. For more than 40 years in rural Pike County, the 3,700-acre Portsmouth Gaseous Diffusion Plant (PORTS), or the “A-Plant” as the locals refer to it, enriched uranium for use in nuclear weapons. While the facility produced nuclear fuel for national security, it simultaneously exposed plant workers to chemicals and radiation and discharged pollution into the surrounding community. The A-Plant is now being demolished and the site repurposed. However, the site continues to affect the community as, for …

Genitourinary Effects Of Smoking In Men: An Alternative Approach To Smoking Cessation Through Patient Education, Michael J. Lawrence

Family Medicine Clerkship Student Projects

Smoking remains a prominent problem in Vermont, especially outside Chittenden County. The genitourinary effects of smoking tend to be poorly appreciated among patients. This presents an opportunity for further patient education and incentivization to quit. This project focused on the genitourinary effects of smoking in men, specifically highlighting how smoking increases risk of bladder cancer, poorer outcomes in prostate cancer, and a higher risk of erectile dysfunction. The project culminated in creation of an educational poster intended for display in patient bathrooms in a medical setting.

Vibrational Spectroscopy Of Liquid Biopsies For Prostate Cancer Diagnosis, Dinesh Medipally, Daniel Cullen, Valérie Untereiner, G.D. Sockalingum, Adrian Maguire, T.N.Q. Nguyen, Jane Bryant, Emma Noone, Shirley Bradshaw, Marie Finn, Mary Dunne, Aoife M. Shannon, John Armstrong, Aidan Meade, Fiona Lyng

Articles

Background: Screening for prostate cancer with prostate specific antigen and digital rectal examination allows early diagnosis of prostate malignancy but has been associated with poor sensitivity and specificity. There is also a considerable risk of over-diagnosis and overtreatment, which highlights the need for better tools for diagnosis of prostate cancer. This study investigates the potential of high throughput Raman and Fourier Transform Infrared (FTIR) spectroscopy of liquid biopsies for rapid and accurate diagnosis of prostate cancer.

Methods: Blood samples (plasma and lymphocytes) were obtained from healthy control subjects and prostate cancer patients. FTIR and Raman spectra were recorded from plasma …

Efficacy Of A Weight Loss Program Prior To Robot Assisted Radical Prostatectomy In Overweight And Obese Men With Prostate Cancer, Rebekah Wilson, Tom Shannon, Emily Calton, Daniel A. Galvao, Dennis Taaffe, Nicolas H. Hart, Philippa Lyons-Wall, Robert U. Newton

Research outputs 2014 to 2021

Background

Obesity in prostate cancer patients is associated with poor prostate-cancer specific outcomes. Exercise and nutrition can reduce fat mass; however, few studies have explored this as a combined pre-surgical intervention in clinical practice.

Purpose

This study examined the efficacy of a weight loss program for altering body composition in prostate cancer patients prior to robot assisted radical prostatectomy (RARP).

Methods

A retrospective analysis of 43 overweight and obese prostate cancer patients, aged 47–80 years, who completed a very low-calorie diet (~3000–4000 kJ) combined with moderate-intensity exercise (90 min/day) prior to RARP. Whole body and regional fat mass (FM) and …

Prostate Cancer Survivorship Essentials Framework: Guidelines For Practitioners, Jeff Dunn, Anna Green, Nicholas Ralph, Robert U. Newton, Andrew Kneebone, Mark Frydenberg, Suzanne K. Chambers

Research outputs 2014 to 2021

© 2020 The Authors BJU International © 2020 BJU International Published by John Wiley & Sons Ltd Objective: To develop contemporary and inclusive prostate cancer survivorship guidelines for the Australian setting. Participants and Methods: A four-round iterative policy Delphi was used, with a 47-member expert panel that included leaders from key Australian and New Zealand clinical and community groups and consumers from diverse backgrounds, including LGBTQIA people and those from regional, rural and urban settings. The first three rounds were undertaken using an online survey (94–96% response) followed by a fourth final face-to-face panel meeting. Descriptors for men’s current prostate …

Case Report: Co-Existence Of Brca2 And Palb2 Germline Mutations In Familial Prostate Cancer With Solitary Lung Metastasis., Tang Tang, Lin-Ang Wang, Peng Wang, Dali Tong, Gaolei Liu, Jun Zhang, Nan Dai, Yao Zhang, Gang Yuan, Kyla Geary, Dianzheng Zhang, Qiuli Liu, Jun Jiang

PCOM Scholarly Papers

Background: Mutation-caused loss-of-function of factors involved in DNA damage response (DDR) is responsible for the development and progression of ~20% of prostate cancer (PCa). Some mutations can be used in cancer risk assessment and informed treatment decisions.

Methods: Target capture-based deep sequencing of 11 genes was conducted with total DNA purified from the proband's peripheral blood. Sanger sequencing was conducted to screen potential germline mutations in the proband's family members. Targeted sequencing of a panel of 1,021 genes was done with DNA purified from the tumor tissue.

Results: Two previously unreported germline mutations in the DDR pathway,

Conclusions: The newly …

Can Exercise Adaptations Be Maintained In Men With Prostate Cancer Following Supervised Programmes? Implications To The Covid-19 Landscape Of Urology And Clinical Exercise, Pedro Lopez, Dennis R. Taaffe, Robert U. Newton, Nigel Spry, Tom Shannon, Mark Frydenberg, Fred Saad, Daniel A. Galvão

Research outputs 2014 to 2021

© 2020 The Author(s) In this brief correspondence, we evaluate the potential impact of pivoting from face-to-face supervised to unsupervised home-based exercise programmes to contextualise the coronavirus disease 2019 (COVID-19) pandemic in prostate cancer patients. A meta-analysis was undertaken in fatigue, quality of life, and lean and fat mass outcomes in the four studies included. Our analysis indicates that unsupervised home-based exercise maintains patient-reported outcomes, except for fat mass. In summary, changing to unsupervised exercise is unlikely to provide further benefits on patient-reported and body composition outcomes, but may help maintain initial gains during physical distancing restrictions. Patient summary: We …

The Effect Of The Senolytic Abt-263 On Androgen Deprivation-Induced Senescent Prostate Tumor Cells, So Min Lee

Theses and Dissertations

Prostate cancer (PCa) is one of the leading causes of cancer-related deaths in men. Although standard treatments such as androgen deprivation therapies (ADT) and antiandrogens have increased survival for many patients, most men placed on these therapies will develop castration-resistant disease (CRPC). Previous studies have shown that these treatments have limited cytotoxicity and instead promote cell growth arrest. Our current work demonstrates that prostate tumor cells grown in the absence of androgens by using charcoal-stripped serum undergo senescence-mediated or senescent-like growth arrest, based on the cellular expression of senescence-associated-beta-galactosidase (SA-β-Gal). Our studies further suggest that this senescence is transient and …

Trajectories In Muscular Strength And Physical Function Among Men With And Without Prostate Cancer In The Health Aging And Body Composition Study, Alexander R. Lucas, Rhonda L. Bitting, Jason Fanning, Scott Isom, W. Jack Rejeski, Heidi D. Klepin, Stephen B. Kritchevsky

Health Behavior and Policy Publications

Objectives

To examine and compare changes in strength and physical function from pre- to post-diagnosis among men with prostate cancer (PC, [cases]) and matched non-cancer controls identified from the Health, Aging and Body Composition (Health ABC) study.

Materials and methods

We conducted a longitudinal analysis of 2 strength and 3 physical function-based measures among both cases and controls, identified from a large cohort of community living older adults enrolled in the Health ABC study. We plotted trajectories for each measure and compared cases vs. controls from the point of diagnosis onwards using mixed-effects regression models. For cases only, we examined …

Angiogenin Mrna Expression Levels In Prostate Cancer Tissue, Bowen Yao, Megumi Shigematsu, Phd, Kamlesh Ganesh Pawar, Phd, Venetia Pliatsika, Ms, Yohei Kirino, Phd

Phase 1

Introduction: Prostate cancer is the most commonly diagnosed cancer in men and second leading cause of cancer deaths. Studies have shown that tRNA fragments are upregulated in prostate cancers and play important roles in carcinogenesis. This project looks at how tRNA cleaving enzyme angiogenin expression is regulated in prostate cancer tissues.

Methods: Clinical data and mRNA expression levels of selected tRNA cleaving enzymes were extracted from the TCGA website. mRNAs were sequenced using IlluminaGA_RNASeqV2 at University of North Carolina.

Results: 546 samples from 494 patients, with normal tissue from 53 patients were collected. ANG mRNA levels were lower in patients …

Impact Of In-House Specialty Pharmacy On Access To Novel Androgen Axis Inhibitors In Men With Advanced Prostate Cancer, Anna Driscoll, Nathan Handley, Md, Mba, Adam Binder, Siobhan Henry, W. Kevin Kelly, Do

Phase 1

Introduction: Novel androgen axis inhibitors are standard of care treatments in advanced prostate cancer. The billed amounts for these medications are often very high, which may create significant financial toxicity for patients and lead to delays in treatment. Our institution implemented an in-house specialty pharmacy in 2014, that provides these medications and evaluates copay assistance options for all patients. We evaluated the program’s impact on out of pocket cost (OOP) and turnaround time (TAT).

Methods: We reviewed available internal specialty pharmacy records to identify prescriptions for abiraterone or enzalutamide filled between 1/1/17 and 12/31/18. Payments were stratified by primary payment …

Manipulation Of Genome Integrity Signaling Axes Contributing To Prostate Cancer Aggressiveness, Frank Duan, Veronica Rodriguez-Bravo, Phd

Phase 1

Introduction: Prostate cancer (PC) is one of the leading causes of death in men, and despite current treatment options patients can develop aggressive disease that spreads to other parts of the body. Little research has focused to date on the effect of centrosome biology in the pathogenesis of PC.

Methods: Two metastatic PC cell lines, DU145 and 22Rv1, as well as highly aggressive derivatives generated in Dr. Rodriguez-Bravo lab (docetaxel-resistant; (DR) variants) were compared through various experiments to determine differences in centrosome proteins expression and functionality. All cells (DU145 /DR and 22Rv1 /DR) underwent electroporations with siRNAs to knockout …

Serum Paraoxonase 1 And 3 Activities In Benign And Malignant Diseases Of The Prostateand Changes In Levels Following Robotic-Assisted Laparoscopic Radical Prostatectomy, Fevzi̇ Bedi̇r, Hüseyi̇n Kocatürk, Mehmet Sefa Altay, Engi̇n Şebi̇n, Banu Bedi̇r

Turkish Journal of Medical Sciences

Background/aim: This study aimed to examine serum paraoxonase 1 and 3 (PON1 and PON3) activities in benign and malignant diseases of the prostate, to determine lipid profile and malondialdehyde (MDA) levels, and to investigate changes in levels following robotic-assisted laparoscopic radical prostatectomy (RALRP). Materials and methods: A total of 137 patients, including a control group, were enrolled in the study and assigned into four groups. Group 1 (n = 33) consisted of patients previously undergoing RALRP with no recurrence, group 2 (n = 36) consisted of patients diagnosed with prostate cancer (PCa) and undergoing RALRP, and group 3 (n = …

Knowledge Levels, Attitude And Beliefs Of Men Towards The Digital Rectal Examinations (Dre): A Study In Trinidad, Philip C. Onuoha, Gloria Mootoo-Ramdeen, Melany Romany, G La Fleur-Roseman, J Roopnarine, D Diaspia-Murrell, K Martin-Boucaud, P Hypolite

Internet Journal of Allied Health Sciences and Practice

Background: Trinidad and Tobago have been ranked as having one of the highest cancer mortality rates in the Caribbean. Prostate cancer was identified as the most common cancer in men, with a higher mortality than any other cancer. At least 1 in 9 men in Trinidad and Tobago will be diagnosed with prostate cancer during his lifetime. Purpose: The purpose of this study is to determine knowledge levels, attitudes, and beliefs of men aged 40 years and over regarding digital rectal examination (DRE). The investigators considered this crucial following the scourge of prostate cancer in Trinidad and Tobago and an …

Exercise And Nutrition Induced Weight Loss For Prostate Cancer Patients, Rebekah Louise Wilson

Theses: Doctorates and Masters

This thesis encompasses six main chapters - two reviews and four experimental chapters, in addition to a general introduction and discussion.

Review 1 (Chapter 2) is a discussion of the negative impact of obesity on prostate cancer prognosis and common prostate cancer treatments.

Review 2 (Chapter 3) is an evaluation of the current literature examining prostate cancer patients receiving androgen deprivation therapy (ADT) and how exercise and nutrition interventions can be used to induce fat loss, while preserving or improving lean mass.

Study 1 (Chapter 4) is an examination of the efficacy of a weight loss program in altering body …