Medicine and Health Sciences Commons^™

Small Extracellular Vesicle-Mediated Itgb6 Sirna Delivery Downregulates The Αvβ6 Integrin And Inhibits Adhesion And Migration Of Recipient Prostate Cancer Cells, Shiv Ram Krishn, Vaughn Garcia, Nicole M Naranjo, Fabio Quaglia, Christopher D Shields, Maisha A Harris, Andrew V Kossenkov, Qin Liu, Eva Corey, Dario C Altieri, Lucia R Languino

Department of Cancer Biology Faculty Papers

The αVβ6 integrin, an epithelial-specific cell surface receptor absent in normal prostate and expressed during prostate cancer (PrCa) progression, is a therapeutic target in many cancers. Here, we report that transcript levels of ITGB6 (encoding the β6 integrin subunit) are significantly increased in metastatic castrate-resistant androgen receptor-negative prostate tumors compared to androgen receptor-positive prostate tumors. In addition, the αVβ6 integrin protein levels are significantly elevated in androgen receptor-negative PrCa patient derived xenografts (PDXs) compared to androgen receptor-positive PDXs. In vitro, the androgen receptor-negative PrCa cells express high levels of the αVβ6 integrin compared to androgen receptor-positive PrCa cells. Additionally, …

Response To Chen Et. Al, Albert Stuart Reece, Gary Kenneth Hulse

Research outputs 2022 to 2026

Whilst our paper was published in three parts to assist with readability it is essentially a single report. Our analysis moves logically from continuous and categorical bivariate studies to inverse probability weighted multivariate (IPWM) and then geospatiotemporal analysis and finally statistical analysis of geospatiotemporal models. Context is important. As stated by Chen and colleagues IPWM models are very powerful and present compelling conclusions and have the effect of transforming ecological into pseudo-randomized studies from which it is entirely proper to draw causal conclusions. That this report follows similar earlier IPWM and geotemporospatial reports on the commonest cancer in adults and …

Experiences Of Participants In A Clinical Trial Of A Novel Radioactive Treatment For Advanced Prostate Cancer: A Nested, Qualitative Longitudinal Study, Bianca Viljoen, Michael S. Hofman, Suzanne K. Chambers, Jeff Dunn, Haryana M. Dhillon, Ian D. Davis, Nicholas Ralph

Research outputs 2022 to 2026

Objectives: Qualitative studies nested within clinical trials can provide insight into the treatment experience, how this evolves over time and where improved supportive care is required. The purpose of this qualitative study is to describe the lived experiences of men with advanced prostate cancer participating in the TheraP trial; a randomised trial of 177Lu-PSMA-617 compared with cabazitaxel chemotherapy. Methods: Fifteen men with advanced prostate cancer were recruited from the TheraP clinical trial with interviews conducted at three timepoints during the trial. An interpretative phenomenological approach was used, and interviews analysed using thematic analysis. This research paper reports the results from …

Theragnostic Radionuclide Pairs For Prostate Cancer Management, Anupriya Chhabra, Mathew L Thakur

Department of Radiology Faculty Papers

Prostate cancer (PCa) is one of the preeminent causes of mortality in men worldwide. Theragnostic, a combination of therapy and diagnostic, using radionuclide pairs to diagnose and treat disease, has been shown to be a promising approach for combating PCa. In PCa patients, bone is one of the most common sites of metastases, and about 90% of patients develop bone metastases. This review focuses on (i) clinically translated theragnostic radionuclide pairs for the management of PCa, (ii) radionuclide therapy of bone metastases in PCa, and (iii) a special emphasis on emerging theragnostic radionuclide pair, Copper-64/Copper-67 (⁶⁴Cu/⁶⁷Cu) …

Impact Of Different Unconditional Monetary Incentives On Survey Response Rates In Men With Prostate Cancer: A 2-Arm Randomised Trial, Megan Mcintosh, Melissa J. Opozda, Michael O’Callaghan, Andrew D. Vincent, Daniel A. Galvão, Camille E. Short

Research outputs 2022 to 2026

Background:

Men are often viewed as a difficult group to recruit for psychological research, including in psycho-oncology. Whilst research has demonstrated the effectiveness of small monetary incentives for encouraging research participation, little research has examined different large unconditional incentive amounts. Larger unconditional incentives may result in increased participation of men in psychological research. This randomised study within a case–control trial of men diagnosed with early-stage prostate cancer aimed to investigate whether (a) response rates to a 30-min questionnaire completed via mail, online, or phone would vary with different unconditional incentive amounts, and (b) demographics would vary in those who responded …

Bone Health Management In The Continuum Of Prostate Cancer Disease, Ettickan Boopathi, Ruth Birbe, Sunday A. Shoyele, Robert B. Den, Thangavel Chellappagounder

Department of Medicine Faculty Papers

Prostate cancer (PCa) is the second-leading cause of cancer-related deaths in men. PCa cells require androgen receptor (AR) signaling for their growth and survival. Androgen deprivation therapy (ADT) is the preferred treatment for patients with locally advanced and metastatic PCa disease. Despite their initial response to androgen blockade, most patients eventually will develop metastatic castration-resistant prostate cancer (mCRPC). Bone metastases are common in men with mCRPC, occurring in 30% of patients within 2 years of castration resistance and in >90% of patients over the course of the disease. Patients with mCRPC-induced bone metastasis develop lesions throughout their skeleton; the 5-year …

Steap1-4 (Six-Transmembrane Epithelial Antigen Of The Prostate 1-4) And Their Clinical Implications For Prostate Cancer, Michael Xu, Latese Evans, Candice L Bizzaro, Fabio Quaglia, Cecilia E Verrillo, Li Li, Julia Stieglmaier, M J Schiewer, Lucia R Languino, William Kevin Kelly

Department of Urology Faculty Papers

Six-Transmembrane Epithelial Antigen of the Prostate 1-4 (STEAP1-4) compose a family of metalloproteinases involved in iron and copper homeostasis and other cellular processes. Thus far, five homologs are known: STEAP1, STEAP1B, STEAP2, STEAP3, and STEAP4. In prostate cancer, STEAP1, STEAP2, and STEAP4 are overexpressed, while STEAP3 expression is downregulated. Although the metalloreductase activities of STEAP1-4 are well documented, their other biological functions are not. Furthermore, the properties and expression levels of STEAP heterotrimers, homotrimers, heterodimers, and homodimers are not well understood. Nevertheless, studies over the last few decades have provided sufficient impetus to investigate STEAP1-4 as potential biomarkers and therapeutic …

Outcomes Following Abiraterone Versus Enzalutamide For Prostate Cancer: A Scoping Review, Yash B, Shah, Amy L. Shaver, Jacob Beiriger, Sagar Mehta, Nikita Nikita, William Kevin Kelly, Stephen J. Freedland, Grace Lu-Yao

Department of Medical Oncology Faculty Papers

Abiraterone acetate (AA) and enzalutamide (ENZ) are commonly used for metastatic prostate cancer. It is unclear how their outcomes and toxicities vary with patient-specific factors because clinical trials typically exclude patients with significant comorbidities. This study aims to fill this knowledge gap and facilitate informed treatment decision making. A registered protocol utilizing PRISMA scoping review methodology was utilized to identify real-world studies. Of 433 non-duplicated publications, 23 were selected by three independent reviewers. ENZ offered a faster and more frequent biochemical response (30-50% vs. 70-75%), slowed progression (HR 0.66; 95% CI 0.50-0.88), and improved overall survival versus AA. ENZ was …

Increased Cytokine Gene Expression And Cognition Risk Associated With Androgen Deprivation Therapy, Shiv Verma, Prem Prakash Kushwaha, Eswar Shankar, Lee E. Ponsky, Sanjay Gupta

Faculty Scholarship

Background: Androgen deprivation therapy (ADT) is a standard treatment modality for locally advanced, high-risk, and metastatic hormone-sensitive prostate cancer. Long-term ADT treatment likely develops side-effects that include changes in cognition or onset of dementia. However, the molecular understanding of this effect remains elusive. We attempt to establish a link between ADT and changes in cognitive function using patient databases and bioinformatics analyses. Methods: Gene expression profiling was performed using RNA sequencing data from Alzheimer patient cohort and compared with the data from advanced-stage prostate cancer patients receiving neoadjuvant antiandrogen therapy. Differentially expressed genes (DEGs) were analyzed using the Ingenuity knowledge …

Identification Of Novel Somatic Fusions Of Erg-Vegfa, Tmprss2-Erg, And Vegfa-Tmprss2 In Prostate Cancer Treated With Anlotinib And Androgen Deprivation Therapy: A Case Report, Qiuli Liu, Shuo Wang, Ze Wang, Peng Tang, Dianzheng Zhang, Weihua Lan, Jun Jiang

PCOM Scholarly Papers

The TMPRSS2-ERG fusion gene has frequently been found in prostate cancer and is associated with malignancy. Identifying novel fusions will help to stratify patients and establish patient-tailored therapies. A 78-year-old man presented to our hospital with severe symptoms of urinary urgency and frequency for 2 years, as well as severe bone pain for 1 year. He was diagnosed with metastatic prostate cancer with a Gleason score of 5 + 5. Three gene fusions, ERG_VEGFA, TMPRSS2_ERG, and VEGFA_TMPRSS2, were identified in the patient's prostate cancer tissue. Notably, administration of the tyrosine kinase inhibitor, anlotinib, in combination with a gonadotropin-releasing hormone agonist …

Variation In Molecularly Defined Prostate Tumor Subtypes By Self-Identified Race, Kevin H. Kensler, H. Lee Moffitt Cancer Center And Research Institute, Mohamed Alshalalfa, Bruce J. Trock, Stephen J. Freedland, Michael R. Freeman, Sungyong You, Brandon A. Mahal, Robert Den, Adam Dicker, R. Jeffrey Karnes, Eric A. Klein, Priti Lal, Yang Liu, Elai Davicioni, Walter Rayford, Kosj Yamoah, Timothy R. Rebbeck

Department of Radiation Oncology Faculty Papers

Background: Socioeconomic and health care utilization factors are major drivers of prostate cancer (PC) mortality disparities in the USA; however, tumor molecular heterogeneity may also contribute to the higher mortality among Black men. Objective: To compare differences in PC subtype frequency and genomic aggressiveness by self-identified race. Design, setting, and participants: Five molecular subtype classifiers were applied for 426 Black and 762 White PC patients in the Decipher Genomics Resource Information Database (GRID). Outcome measurements and statistical analysis: Differences in subtype frequency and tumor genomic risk (Decipher score >0.6) by race were evaluated using χ2 tests and multivariable-adjusted logistic regression …

Intake Patterns Of Specific Alcoholic Beverages By Prostate Cancer Status, Hui Yi Lin, Tung-Sung Tseng, Xinnan Wang, Zhide Fang, Arnold H. Zea, Liang Wang, Julio Pow-Sang, Catherine M. Tangen, Phyllis J. Goodman, Alicja Wolk, Niclas Håkansson, Manolis Kogevinas, Javier Llorca, Hermann Brenner, Ben Schöttker, Jose Esteban Castelao, Manuela Gago-Dominguez, Marija Gamulin, Davor Lessel, Frank Claessens, Steven Joniau, Jong Y. Park

School of Public Health Faculty Publications

Background: Previous studies have shown that different alcoholic beverage types impact prostate cancer (PCa) clinical outcomes differently. However, intake patterns of specific alcoholic beverages for PCa status are understudied. The study’s objective is to evaluate intake patterns of total alcohol and the three types of beverage (beer, wine, and spirits) by the PCa risk and aggressiveness status. Method: This is a cross-sectional study using 10,029 men (4676 non-PCa men and 5353 PCa patients) with European ancestry from the PCa consortium. Associations between PCa status and alcohol intake patterns (infrequent, light/moderate, and heavy) were tested using multinomial logistic regressions. Results: Intake …

Modulating Tumour Hypoxia In Prostate Cancer Through Exercise: The Impact Of Redox Signalling On Radiosensitivity, Malcolm Brown, Amélie Rébillard, Nicolas H. Hart, Dominic O’Connor, Gillian Prue, Joe M. O’Sullivan, Suneil Jain

Research outputs 2022 to 2026

Prostate cancer is a complex disease affecting millions of men globally. Radiotherapy (RT) is a common treatment modality although treatment efficacy is dependent upon several features within the tumour microenvironment (TME), especially hypoxia. A hypoxic TME heightens radioresistance and thus disease recurrence and treatment failure continues to pose important challenges. However, the TME evolves under the influence of factors in systemic circulation and cellular crosstalk, underscoring its potential to be acutely and therapeutically modified. Early preclinical evidence suggests exercise may affect tumour growth and some of the benefits drawn, could act to radiosensitise tumours to treatment. Intracellular perturbations in skeletal …

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 …

Construction Of A Repeatable Framework For Prostate Cancer Lesion Binary Semantic Segmentation Using Convolutional Neural Networks, Ian Vincent O. Mirasol, Patricia Angela R. Abu, Rosula Sj Reyes

Department of Information Systems & Computer Science Faculty Publications

Prostate cancer is the 3rd most diagnosed cancer overall. Current screening methods such as the prostate-specific antigen test could result in overdiagonosis and overtreatment while other methods such as a transrectal ultrasonography are invasive. Recent medical advancements have allowed the use of multiparametric MRI — a noninvasive and reliable screening process for prostate cancer. However, assessment would still vary from different professionals introducing subjectivity. While con-volutional neural network has been used in multiple studies to ob-jectively segment prostate lesions, due to the sensitivity of datasets and varying ground-truth established used in these studies, it is not possible to reproduce and …

Why Do Men With Prostate Cancer Discontinue Active Surveillance For Definitive Treatment? A Mixed Methods Investigation, Megan Mcintosh, Melissa J. Opozda, Michael O’Callaghan, Andrew D. Vincent, Daniel A. Galvão, Camille E. Short

Research outputs 2022 to 2026

Objectives: To explore the personal and/or medical reasons patients on active surveillance (AS) have, or consider having, further definitive treatment for their prostate cancer. Research suggests up to 50% of patients on AS will discontinue within 5 years, though reasons for discontinuation from the patient's perspective is under-explored. Methods: Prostate cancer patients who were or had been on AS for at least 6 months were recruited. A questionnaire assessed reasons for receiving/considering definitive treatment and the extent to which reasons were personal or medical. Clinical information was extracted from a state-level population registry. A subset of participants were interviewed to …