Translational Medical Research Commons^™

Differential Gene Expression Between African American And Caucasian American Prostate Cancer, Daniel L. Shen, Gregory T. Maclennan, Sanjay Gupta

Research Symposium

Background: African-American (AA) men have higher incidence and mortality from prostate cancer compared to Caucasian-American (CA) men. Increasing evidence suggests that genetic and molecular alterations play important roles. We identified a 5 gene panel viz. p-Akt (Ser473), chemokine (C-X-C motif) receptor 4 (CXCR4), fatty acid synthase (FASN), interleukin-6 (IL-6) and matrix metallopeptidase 9 (MMP-9) highly expressed in prostate cancer and analyzed their expression in AA and CA cohorts.

Methods: IHC of p-Akt, CXCR4, FASN, IL-6 and MMP-9 were evaluated in RRP specimens (n=20) from each ethnic group exhibiting Gleason scores ranging from 6 through 9.

Results: Low to medium staining …

External Beam Radiation Therapy Carries Lower Risk Of Sexual Dysfunction As Compared To Radical Prostatectomy In Treatment Of Patients With Localized Prostate Cancer, Aamod S. Dekhne

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report appraising:

Donovan JL, Hamdy FC, Lane JA, et al. Patient-Reported Outcomes after Monitoring, Surgery, or Radiotherapy for Prostate Cancer. N Engl J Med. 2016;375(15):1425-1437. https://doi.org/10.1056/NEJMoa1606221

for a patient with localized prostate cancer and concerns regarding future sexual dysfunction.

Nccn Intermediate Risk Prostate Cancer- Long-Term Outcomes Of Active Surveillance Compared To Active Treatment, A Population-Based Analysis, Adam Schneider, Thenappan Chandrasekar, Nicholas Bowler, Hanan Goldberg, James R. Mark, Edouard J. Trabulsi, Costas D. Lallas, Leonard G. Gomella

Phase 1

Background: While active surveillance (AS) is an established standard of care for low-risk (LR) prostate cancer (PCa), its utility for intermediate risk (IR) PCa is less evident. Prior studies were limited by the inability to differentiate between AS and watchful waiting (WW). Using a recent update in the Surveillance, Epidemiology and End Results (SEER) Database that allows for enhanced distinction between AS and WW, we aimed to compare survival outcomes of men with LR and IR PCa treated with either AS, WW or active treatment (AT).

Methods: 166,244 men were initially identified by biopsy Gleason Grade Group (GG) alone – …

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 …

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 …

Relevance Of Fgfr1 And Its Isoforms In Prostate Cancer Bone Metastases, Estefania Labanca

Dissertations & Theses (Open Access)

The fibroblast growth factor receptor (FGFR) 1 is implicated in prostate cancer (PCa) progression. Various FGFR1 isoforms have been described and we demonstrate here that the well-characterized FGFR1 a and b isoforms are correlated with the expression of different genes and pathways in human PCa. Direct injection of PC3 PCa cells overexpressing FGFR1 isoforms into the femur of mice resulted in enhanced tumor growth and reduction in bone volume when compared with PC3 expressing empty vector. However, only PC3 overexpressing FGFR1 b was associated with increased osteoclast parameters, suggesting that each isoform may mediate diverse biological effects (similar findings were …

P53r245w Mutation Elicits Metastatic Phenotype In Pten Deficient Prostate Cancer, Ky Pham

Dissertations & Theses (Open Access)

Trp53 mutations are the most frequent genetic alterations in prostate cancer and are associated with more aggressive disease and worse overall survival. The majority of Trp53 mutations in prostate cancer are missense mutations, resulting in amino acid substitutions with profound effect. In addition to the loss of wild type function, missense mutations in Trp53 result in a gain-of-function (GOF) phenotype. This GOF phenotype confers biologic advantages to the tumor cells, enabling them to metastasize and invade distant organs. In this study, we generated mice carrying a conditional prostate-specific p53R245W mutant and Pten deletion to access the role of this common …

Development Of Mithramycin Analogues With Improved Efficacy And Reduced Toxicity For Treatment Of Ets-Dependent Tumors In Ewing Sarcoma And Prostate Cancer, Joseph Michael Eckenrode

Theses and Dissertations--Pharmacy

Introduction: Genetic rearrangements in Ewing sarcoma, prostate, and leukemia cells result in activation of oncogenic ETS transcription factor fusions. Mithramycin (MTM) has been identified as an inhibitor of EWS-FLI1 transcription factor, a gene fusion product responsible for oncogenesis in Ewing sarcoma. Despite preclinical success, a phase I/II clinical trial testing MTM therapy in refractory Ewing sarcoma was terminated. Liver and blood toxicities resulted in dose de-escalation and sub-therapeutic exposures. However, the promise of selectively targeting oncogenic ETS transcription factors like EWS-FLI1 prompted us to undertake the discovery of more selective, less toxic analogues of MTM. MTM is a potent inhibitor …

Microrna 1207-3p In Prostate Cancer, Dibash Das

Dissertations, Theses, and Capstone Projects

Prostate cancer (PCa) is the most commonly diagnosed male cancer and the second leading cause of cancer-related death for men in the United States. Understanding the molecular mechanisms involved in progression from the asymptomatic androgen-dependent PCa to the lethal castration resistant prostate cancer (CRPC) is a major challenge. MicroRNAs (miRNAs), are known to be dysregulated in PCa. MicroRNA-1207-3p (miR-1207-3p) is encoded by the non-protein coding gene locus PVT1 on the 8q24 human chromosomal region, an established PCa susceptibility locus. However, the role of miR-1207-3p in PCa is unclear. We have discovered that miR-1207-3p is significantly underexpressed in PCa cell lines …

Anticancer Effect Of Moringa Oleifera Leaf Extract In Human Cancer Cell Lines, María Del Mar Zayas-Viera, Pablo Vivas-Mejia, Ph.D, Jeyshka Reyes, Phd

Journal of Health Disparities Research and Practice

Many medicinal plants are used as chemo preventives and antitumor agents in numerous experimental models of carcinogenesis. Moringa oleifera is a plant that contains several phytochemicals, which have been used for medical purposes including anti-inflammatory, analgesic, metabolism activator, anti-asthmatic, anti-anemia, hormone-producing, liver protector, and detoxifier, among others. Moringa oleifera extracts have also been proposed as potential anticancer agents. Cancer is one of the main causes of deaths worldwide. Although many drugs exist against several types of cancer, more specific agents with lower side effects are necessary. Few reports exist regarding the antitumor activity of Moringa oleifera leaf extract in cancer …

Evidence-Based Practice In The New Millenium, Nicholus H. Yee

Clinical Research in Practice: The Journal of Team Hippocrates

A reflection on learning and education in practice.