IU Indianapolis ScholarWorks :: Browsing by Subject "Prostate"

Browsing by Subject "Prostate"

Now showing 1 - 10 of 16

The common parasite Toxoplasma gondii induces prostatic inflammation and microglandular hyperplasia in a mouse model
(Wiley, 2017-07) Colinot, Darrelle L.; Garbuz, Tamila; Bosland, Maarten C.; Wang, Liang; Rice, Susan E.; Sullivan, William J., Jr.; Arrizabalaga, Gustavo; Jerde, Travis J.; Pharmacology and Toxicology, School of Medicine
BACKGROUND: Inflammation is the most prevalent and widespread histological finding in the human prostate, and associates with the development and progression of benign prostatic hyperplasia and prostate cancer. Several factors have been hypothesized to cause inflammation, yet the role each may play in the etiology of prostatic inflammation remains unclear. This study examined the possibility that the common protozoan parasite Toxoplasma gondii induces prostatic inflammation and reactive hyperplasia in a mouse model. METHODS: Male mice were infected systemically with T. gondii parasites and prostatic inflammation was scored based on severity and focality of infiltrating leukocytes and epithelial hyperplasia. We characterized inflammatory cells with flow cytometry and the resulting epithelial proliferation with bromodeoxyuridine (BrdU) incorporation. RESULTS: We found that T. gondii infects the mouse prostate within the first 14 days of infection and can establish parasite cysts that persist for at least 60 days. T. gondii infection induces a substantial and chronic inflammatory reaction in the mouse prostate characterized by monocytic and lymphocytic inflammatory infiltrate. T. gondii-induced inflammation results in reactive hyperplasia, involving basal and luminal epithelial proliferation, and the exhibition of proliferative inflammatory microglandular hyperplasia in inflamed mouse prostates. CONCLUSIONS: This study identifies the common parasite T. gondii as a new trigger of prostatic inflammation, which we used to develop a novel mouse model of prostatic inflammation. This is the first report that T. gondii chronically encysts and induces chronic inflammation within the prostate of any species. Furthermore, T. gondii-induced prostatic inflammation persists and progresses without genetic manipulation in mice, offering a powerful new mouse model for the study of chronic prostatic inflammation and microglandular hyperplasia.
Comparison of Contemporary Surgical Outcomes Between Holmium Laser Enucleation of the Prostate and Robotic-Assisted Simple Prostatectomy
(Springer Nature, 2023) Shelton, T. Max; Drake, Connor; Vasquez, Ruben; Rivera, Marcelino; Urology, School of Medicine
Purpose of review: This study reviews contemporary literature on RASP and HoLEP to evaluate perioperative outcomes, common complications, cost analytics, and future directions of both procedures. Recent findings: RASP is indicated for prostates > 80 mL, while HoLEP is size-independent. No notable differences were found in operative time, PSA nadir (surrogate for enucleation volume), re-catheterization rates, or long-term durability. Prolonged incontinence and bladder neck contracture rates are low for both surgeries. Patients experience similar satisfaction outcomes and improvements in uroflowmetry and post-void residual volumes. HoLEP demonstrates shorter hospitalizations, lower transfusion rates, lower costs, and higher rates of same-day discharge. RASP offers a shorter learning curve and lower rates of early postoperative urinary incontinence. HoLEP is a size-independent surgery that offers advantages for patients seeking a minimally invasive procedure with the potential for catheter-free same-day discharge. Future directions with single-port simple prostatectomy may offer parity in same-day discharge, but further research is needed to determine broader feasibility.
Coordinated induction of cell survival signaling in the inflamed microenvironment of the prostate
(Wiley, 2016-06) McIlwain, David W.; Zoetemelk, Marloes; Myers, Jason D.; Edwards, Marshé T.; Snider, Brandy M.; Jerde, Travis J.; Pharmacology and Toxicology, School of Medicine
PURPOSE: Both prostate cancer and benign prostatic hyperplasia are associated with inflammatory microenvironments. Inflammation is damaging to tissues, but it is unclear how the inflammatory microenvironment protects specialized epithelial cells that function to proliferate and repair the tissue. The objective of this study is to characterize the cell death and cell survival response of the prostatic epithelium in response to inflammation. METHODS: We assessed induction of cell death (TNF, TRAIL, TWEAK, FasL) and cell survival factors (IGFs, hedgehogs, IL-6, FGFs, and TGFs) in inflamed and control mouse prostates by ELISA. Cell death mechanisms were determined by immunoblotting and immunofluorescence for cleavage of caspases and TUNEL. Survival pathway activation was assessed by immunoblotting and immunofluorescence for Mcl-1, Bcl-2, Bcl-XL, and survivin. Autophagy was determined by immunoblotting and immunofluorescence for free and membrane associated light chain 3 (LC-3). RESULTS: Cleavage of all four caspases was significantly increased during the first 2 days of inflammation, and survival protein expression was substantially increased subsequently, maximizing at 3 days. By 5 days of inflammation, 50% of prostatic epithelial cells expressed survivin. Autophagy was also evident during the recovery phase (3 days). Finally, immunofluorescent staining of human specimens indicates strong activation of survival proteins juxtaposed to inflammation in inflamed prostate specimens. CONCLUSIONS: The prostate responds to deleterious inflammation with induction of cell survival mechanisms, most notably survivin and autophagy, demonstrating a coordinated induction of survival factors that protects and expands a specialized set of prostatic epithelial cells as part of the repair and recovery process during inflammation.
Genetic Factors Associated with Prostate Cancer Conversion from Active Surveillance to Treatment
(Elsevier, 2022) Jiang, Yu; Meyers, Travis J.; Emeka, Adaeze A.; Folgosa Cooley, Lauren; Cooper, Phillip R.; Lancki, Nicola; Helenowski, Irene; Kachuri, Linda; Lin, Daniel W.; Stanford, Janet L.; Newcomb, Lisa F.; Kolb, Suzanne; Finelli, Antonio; Fleshner, Neil E.; Komisarenko, Maria; Eastham, James A.; Ehdaie, Behfar; Benfante, Nicole; Logothetis, Christopher J.; Gregg, Justin R.; Perez, Cherie A.; Garza, Sergio; Kim, Jeri; Marks, Leonard S.; Delfin, Merdie; Barsa, Danielle; Vesprini, Danny; Klotz, Laurence H.; Loblaw, Andrew; Mamedov, Alexandre; Goldenberg, S. Larry; Higano, Celestia S.; Spillane, Maria; Wu, Eugenia; Carter, H. Ballentine; Pavlovich, Christian P.; Mamawala, Mufaddal; Landis, Tricia; Carroll, Peter R.; Chan, June M.; Cooperberg, Matthew R.; Cowan, Janet E.; Morgan, Todd M.; Siddiqui, Javed; Martin, Rabia; Klein, Eric A.; Brittain, Karen; Gotwald, Paige; Barocas, Daniel A.; Dallmer, Jeremiah R.; Gordetsky, Jennifer B.; Steele, Pam; Kundu, Shilajit D.; Stockdale, Jazmine; Roobol, Monique J.; Venderbos, Lionne D.F.; Sanda, Martin G.; Arnold, Rebecca; Patil, Dattatraya; Evans, Christopher P.; Dall’Era, Marc A.; Vij, Anjali; Costello, Anthony J.; Chow, Ken; Corcoran, Niall M.; Rais-Bahrami, Soroush; Phares, Courtney; Scherr, Douglas S.; Flynn, Thomas; Karnes, R. Jeffrey; Koch, Michael; Dhondt, Courtney Rose; Nelson, Joel B.; McBride, Dawn; Cookson, Michael S.; Stratton, Kelly L.; Farriester, Stephen; Hemken, Erin; Stadler, Walter M.; Pera, Tuula; Banionyte, Deimante; Bianco, Fernando J., Jr.; Lopez, Isabel H.; Loeb, Stacy; Taneja, Samir S.; Byrne, Nataliya; Amling, Christopher L.; Martinez, Ann; Boileau, Luc; Gaylis, Franklin D.; Petkewicz, Jacqueline; Kirwen, Nicholas; Helfand, Brian T.; Xu, Jianfeng; Scholtens, Denise M.; Catalona, William J.; Witte, John S.; Urology, School of Medicine
Men diagnosed with low-risk prostate cancer (PC) are increasingly electing active surveillance (AS) as their initial management strategy. While this may reduce the side effects of treatment for PC, many men on AS eventually convert to active treatment. PC is one of the most heritable cancers, and genetic factors that predispose to aggressive tumors may help distinguish men who are more likely to discontinue AS. To investigate this, we undertook a multi-institutional genome-wide association study (GWAS) of 5,222 PC patients and 1,139 other patients from replication cohorts, all of whom initially elected AS and were followed over time for the potential outcome of conversion from AS to active treatment. In the GWAS we detected 18 variants associated with conversion, 15 of which were not previously associated with PC risk. With a transcriptome-wide association study (TWAS), we found two genes associated with conversion (MAST3, p = 6.9 × 10−7 and GAB2, p = 2.0 × 10−6). Moreover, increasing values of a previously validated 269-variant genetic risk score (GRS) for PC was positively associated with conversion (e.g., comparing the highest to the two middle deciles gave a hazard ratio [HR] = 1.13; 95% confidence interval [CI] = 0.94–1.36); whereas decreasing values of a 36-variant GRS for prostate-specific antigen (PSA) levels were positively associated with conversion (e.g., comparing the lowest to the two middle deciles gave a HR = 1.25; 95% CI, 1.04–1.50). These results suggest that germline genetics may help inform and individualize the decision of AS—or the intensity of monitoring on AS—versus treatment for the initial management of patients with low-risk PC.
Inflammation by Toxoplasma gondii Infection Induces Prostatic Hyperplasia and Accompanying Urinary Dysfunction
(2024-08) Stanczak, Emily F.; Arrizabalaga, Gustavo; Bauer, Margaret; Jerde, Travis; Nakshatri, Harikrishna
Benign prostatic hyperplasia is the non-cancerous enlargement of the prostate. This syndrome develops as men age and affects 50% of men by the age of 50 and 80% of men by the age of 80. BPH is associated with a pattern of symptoms and pathology in patients that can be painful, problematic, and lower the quality of life. BPH is a multifactorial disease which may develop due to lifestyle choices, genetics, metabolic disorder, and potentially infection of the organ. Interestingly, previous work from our research group showed that the common parasite T. gondii can infect and establish a chronic infection in the prostate of mice resulting in histological hyperplasia and glandular nodule formation, reminiscent of that observed in men with BPH. This leads to the hypothesis that T. gondii contributes to BPH in humans. In this work, we investigated whether there is a correlation between T. gondii infection and BPH using a cohort of age matched BPH diagnosed and non-BPH diagnosed control donors. My data show that men diagnosed with BPH are significantly more likely to have evidence of T. gondii infection than undiagnosed controls. Additionally, men with antibodies against T. gondii and BPH had significantly more severe pathology in several categories including and most notably in epithelial and glandular nodules seen only in a steroid hormone model of the disease. Moreover, I have determined that mice infected with parasites demonstrated abnormal urination pattern behavior indicating lower urinary tract dysfunction. Based on these results, we conclude that T. gondii can contribute to the development and severity of BPH and BPH pathology in humans. In addition, T. gondii can potentially be used as a model for BPH and BPH-like symptoms and pathology in mice and other model organisms.
Inflammation Impacts Androgen Receptor Signaling in Basal Prostate Stem Cells Through Interleukin 1 Receptor Antagonist
(Research Square, 2023-12-15) Cooper, Paula O.; Yang, Jiang; Wang, Hsing-Hui; Broman, Meaghan M.; Awdalkreem, Gada D.; Cresswell, Gregory M.; Wang, Liang; Goossens, Emery; Lanman, Nadia A.; Doerge, Rebecca W.; Zheng, Faye; Cheng, Liang; Crist, Scott A.; Braun, Robert E.; Jerde, Travis J.; Ratliff, Timothy L.; Pharmacology and Toxicology, School of Medicine
The majority of patients with benign prostate hyperplasia (BPH) exhibit chronic prostate inflammation and the extent of inflammation correlates with the severity of symptoms. How inflammation contributes to prostate enlargement and/or BPH symptoms and the underlying mechanisms are not clearly understood. We established a unique mouse model Prostate Ovalbumin Expressing Transgenic 3 (POET3) that mimics chronic non-bacterial prostatitis in men to study the role of inflammation in prostate hyperplasia. After the injection of ovalbumin peptide-specific T cells, POET3 prostates exhibited an influx of inflammatory cells and an increase in pro-inflammatory cytokines that led to epithelial and stromal hyperplasia. We have previously demonstrated with the POET3 model that inflammation expands the basal prostate stem cell (bPSC) population and promotes bPSC differentiation in organoid cultures. In this study, we investigated the mechanisms underlying the impact of inflammation on bPSC. We found that AR activity was enhanced in inflamed bPSC and was essential for bPSC differentiation in organoid cultures. Most importantly, we identified, for the first time, interleukin 1 receptor antagonist (IL-1RA) as a key regulator of AR in basal stem cells. IL-1RA was one of the top genes upregulated by inflammation and inhibition of IL-1RA abrogated the enhanced AR nuclear accumulation and activity in organoids derived from inflamed bPSC. The mirroring effects of IL-1RA recombinant protein and IL-1α neutralizing antibody suggest that IL-1RA may function by antagonizing IL-1α inhibition of AR expression. Furthermore, we established a lineage tracing model to follow bPSC during inflammation and under castrate conditions. We found that inflammation induced bPSC proliferation and differentiation into luminal cells even under castrate conditions, indicating that AR activation driven by inflammation in bPSC is sufficient for their proliferation and differentiation under androgen-deprived conditions. However, proliferation of the differentiated bPSC in the luminal layer significantly diminished with castration, suggesting inflammation may not maintain AR activity in stromal cells, as stromal cells deprived of androgen after castration could no longer provide paracrine growth factors essential for luminal proliferation. Taken together, we have discovered novel mechanisms through which inflammation modulates AR signaling in bPSC and induces bPSC luminal differentiation that contributes to prostate hyperplasia.
Inflammation impacts androgen receptor signaling in basal prostate stem cells through interleukin 1 receptor antagonist
(Springer Nature, 2024-10-25) Cooper, Paula O.; Yang, Jiang; Wang, Hsing-Hui; Broman, Meaghan M.; Jayasundara, Shyaman Madhawa; Sahoo, Subhransu Sekhar; Yan, Bingyu; Awdalkreem, Gada D.; Cresswell, Gregory M.; Wang, Liang; Goossens, Emery; Lanman, Nadia A.; Doerge, Rebecca W.; Zheng, Faye; Cheng, Liang; Alqahtani, Saeed; Crist, Scott A.; Braun, Robert E.; Kazemian, Majid; Jerde, Travis J.; Ratliff, Timothy L.; Microbiology and Immunology, School of Medicine
Chronic prostate inflammation in patients with benign prostate hyperplasia (BPH) correlates with the severity of symptoms. How inflammation contributes to prostate enlargement and/or BPH symptoms and the underlying mechanisms remain unclear. In this study, we utilize a unique transgenic mouse model that mimics chronic non-bacterial prostatitis in men and investigate the impact of inflammation on androgen receptor (AR) in basal prostate stem cells (bPSC) and their differentiation in vivo. We find that inflammation significantly enhances AR levels and activity in bPSC. More importantly, we identify interleukin 1 receptor antagonist (IL-1RA) as a crucial regulator of AR in bPSC during inflammation. IL-1RA is one of the top molecules upregulated by inflammation, and inhibiting IL-1RA reverses the enhanced AR activity in organoids derived from inflamed bPSC. Additionally, IL-1RA appears to activate AR by counteracting IL-1α's inhibitory effect. Furthermore, using a lineage tracing model, we observe that inflammation induces bPSC proliferation and differentiation into luminal cells even under castrate conditions, indicating that AR activation driven by inflammation is sufficient to promote bPSC proliferation and differentiation. Taken together, our study uncovers mechanisms through which inflammation modulates AR signaling in bPSC and induces bPSC luminal differentiation that may contribute to prostate hyperplasia.
Intraductal carcinoma of the prostate is not a diagnostic entity
(Wiley, 2021) Delahunt, Brett; Egevad, Lars; Samaratunga, Hemamali; Srigley, John R.; Cheng, Liang; Clouston, David; Furusato, Bungo; Kench, James; Leite, Katia R. M.; MacLennan, Gregory T.; Moch, Holger; Pan, Chin-Chen; Ro, Jae; Tsuzuki, Toyonori; van der Kwast, Theodorus; Wheeler, Thomas; Yaxley, John W.; Pathology and Laboratory Medicine, School of Medicine
Phase II randomized, double-blind, placebo-controlled study of tivantinib in men with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC)
(Springer Nature, 2018-10) Monk, Paul; Liu, Glenn; Stadler, Walter M.; Geyer, Susan; Huang, Ying; Wright, John; Villalona-Calero, Miguel; Wade, James; Szmulewitz, Russell; Gupta, Shilpa; Mortazavi, Amir; Dreicer, Robert; Pili, Roberto; Dawson, Nancy; George, Saby; Garcia, Jorge A.; Medicine, School of Medicine
Background Tivantinib is a non-ATP competitive inhibitor of c-MET receptor tyrosine kinase that may have additional cytotoxic mechanisms including tubulin inhibition. Prostate cancer demonstrates higher c-MET expression as the disease progresses to more advanced stages and to a castration resistant state. Methods 80 patients (pts) with asymptomatic or minimally symptomatic mCRPC were assigned (2:1) to either tivantinib 360 mg PO BID or placebo (P). The primary endpoint was progression free survival (PFS). Results Of the 80 pts. enrolled, 78 (52 tivantinib, 26 P) received treatment and were evaluable. Median follow up is 8.9 months (range: 2.3 to 19.6 months). Patients treated with tivantinib had significantly better PFS vs. those treated with placebo (medians: 5.5 mo vs 3.7 mo, respectively; HR = 0.55, 95% CI: 0.33 to 0.90; p = 0.02). Grade 3 febrile neutropenia was seen in 1 patient on tivantinib while grade 3 and 4 neutropenia was recorded in 1 patient each on tivantinib and placebo. Grade 3 sinus bradycardia was recorded in two men on the tivantinib arm. Conclusions Tivantinib has mild toxicity and improved PFS in men with asymptomatic or minimally symptomatic mCRPC.
Photoacoustic tomography of intact human prostates and vascular texture analysis identify prostate cancer biopsy targets
(Elsevier, 2018-08-03) Bungart, Brittani L.; Lan, Lu; Wang, Pu; Li, Rui; Koch, Michael O.; Cheng, Liang; Masterson, Timothy A.; Dundar, Murat; Cheng, Jin-Xin; Urology, School of Medicine
Prostate cancer is poorly visualized on ultrasonography (US) so that current biopsy requires either a templated technique or guidance after fusion of US with magnetic resonance imaging. Here we determined the ability for photoacoustic tomography (PAT) and US followed by texture-based image processing to identify prostate biopsy targets. K-means clustering feature learning and testing was performed on separate datasets comprised of 1064 and 1197 nm PAT and US images of intact, ex vivo human prostates. 1197 nm PAT was found to not contribute to the feature learning, and thus, only 1064 nm PAT and US images were used for final feature testing. Biopsy targets, determined by the tumor-assigned pixels' center of mass, located 100% of the primary lesions and 67% of the secondary lesions. In conclusion, 1064 nm PAT and US texture-based feature analysis provided successful prostate biopsy targets.

Browsing by Subject "Prostate"

Results Per Page

Sort Options