Browsing by Subject "prostate cancer"

Now showing 1 - 6 of 6
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    A Testosterone Metabolite 19-Hydroxyandrostenedione Induces Neuroendocrine Trans-Differentiation of Prostate Cancer Cells via an Ectopic Olfactory Receptor.
    (Frontiers in oncology, 2018-01) Abaffy, Tatjana; Bain, James R; Muehlbauer, Michael J; Spasojevic, Ivan; Lodha, Shweta; Bruguera, Elisa; O'Neal, Sara K; Kim, So Young; Matsunami, Hiroaki
    Olfactory receptor OR51E2, also known as a Prostate Specific G-Protein Receptor, is highly expressed in prostate cancer but its function is not well understood. Through in silico and in vitro analyses, we identified 24 agonists and 1 antagonist for this receptor. We detected that agonist 19-hydroxyandrostenedione, a product of the aromatase reaction, is endogenously produced upon receptor activation. We characterized the effects of receptor activation on metabolism using a prostate cancer cell line and demonstrated decreased intracellular anabolic signals and cell viability, induction of cell cycle arrest, and increased expression of neuronal markers. Furthermore, upregulation of neuron-specific enolase by agonist treatment was abolished in OR51E2-KO cells. The results of our study suggest that OR51E2 activation results in neuroendocrine trans-differentiation. These findings reveal a new role for OR51E2 and establish this G-protein coupled receptor as a novel therapeutic target in the treatment of prostate cancer.
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    Caring for Alaska Native prostate cancer survivors in primary care: a survey of Alaska Tribal Health System providers.
    (Int J Circumpolar Health, 2014) Tilburt, Jon C; Kelley, Stacy; DeCourtney, Christine A; Humeniuk, Katherine M; Latini, Jerilyn; Kim, Simon P
    BACKGROUND: Little is known about the constraints of optimizing health care for prostate cancer survivors in Alaska primary care. OBJECTIVE: To describe the experiences and attitudes of primary care providers within the Alaska Tribal Health System (ATHS) regarding the care of prostate cancer survivors. DESIGN: In late October 2011, we emailed a 22-item electronic survey to 268 ATHS primary care providers regarding the frequency of Prostate Specific Antigen (PSA) monitoring for a hypothetical prostate cancer survivor; who should be responsible for the patient's life-long prostate cancer surveillance; who should support the patient's emotional and medical needs as a survivor; and providers' level of comfort addressing recurrence monitoring, erectile dysfunction, urinary incontinence, androgen deprivation therapy, and emotional needs. We used simple logistic regression to examine the association between provider characteristics and their responses to the survivorship survey items. RESULTS: Of 221 individuals who were successfully contacted, a total of 114 responded (52% response rate). Most ATHS providers indicated they would order a PSA test every 12 months (69%) and believed that, ideally, the hypothetical patient's primary care provider should be responsible for his life-long prostate cancer surveillance (60%). Most providers reported feeling either "moderately" or "very" comfortable addressing topics such as prostate cancer recurrence (59%), erectile dysfunction (64%), urinary incontinence (63%), and emotional needs (61%) with prostate cancer survivors. These results varied somewhat by provider characteristics including female sex, years in practice, and the number of prostate cancer survivors seen in their practice. CONCLUSIONS: These data suggest that most primary care providers in Alaska are poised to assume the care of prostate cancer survivors locally. However, we also found that large minorities of providers do not feel confident in their ability to manage common issues in prostate cancer survivorship, implying that continued access to specialists with more expert knowledge would be beneficial.
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    Ephrin B Activate Src Family Kinases in Fibroblasts Inducing Stromal Remodeling in Prostate Cancer.
    (Cancers, 2022-05) Kakarla, Mamatha; ChallaSivaKanaka, Sathyavathi; Dufficy, Mary F; Gil, Victoria; Filipovich, Yana; Vickman, Renee; Crawford, Susan E; Hayward, Simon W; Franco, Omar E
    Through stromal-epithelial interactions, carcinoma associated fibroblasts (CAF) play a critical role in tumor growth and progression. Activation of erythrophoyetin-producing human hepatocellular (Eph) receptors has been implicated in cancer. Eph receptor interactions with Ephrin ligands lead to bidirectional signals in the recipient and effector cells. The consequences of continuous reverse Ephrin signaling activation in fibroblasts on prostate cancer (PCa) is unknown. When compared to benign prostate fibroblast, CAF displayed higher expression of Ephrin B1, B2, and B3 ligands (EFNB1, EFNB2, and EFNB3). In this study, we found that continuous activation of EFNB1 and EFNB3 in a benign human prostate stromal cell line (BHPrS1) increased the expression of CAF markers and induced a CAF phenotype. BHPrS1EFNB1 and BHPrS1EFNB3 displayed a pro-tumorigenic secretome with multiple effects on neovascularization, collagen deposition, and cancer cell proliferation, overall increasing tumorigenicity of a premalignant prostate epithelial cell line BPH1 and PCa cell line LNCaP, both in vitro and in vivo. Inhibition of Src family kinases (SFK) in BHPrS1EFNB1 and BHPrS1EFNB3 suppressed EFNB-induced ɑ-SMA (Alpha-smooth muscle actin) and TN-C (Tenascin-C) in vitro. Our study suggests that acquisition of CAF characteristics via SFK activation in response to increased EFNB ligands could promote carcinogenesis via modulation of TME in PCa.
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    Incorporating Case-Based Reasoning for Radiation Therapy Knowledge Modeling: A Pelvic Case Study.
    (Technology in cancer research & treatment, 2019-01) Sheng, Yang; Zhang, Jiahan; Wang, Chunhao; Yin, Fang-Fang; Wu, Q Jackie; Ge, Yaorong
    Knowledge models in radiotherapy capture the relation between patient anatomy and dosimetry to provide treatment planning guidance. When treatment schemes evolve, existing models struggle to predict accurately. We propose a case-based reasoning framework designed to handle novel anatomies that are of same type but vary beyond original training samples. A total of 105 pelvic intensity-modulated radiotherapy cases were analyzed. Eighty cases were prostate cases while the other 25 were prostate-plus-lymph-node cases. We simulated 4 scenarios: Scarce scenario, Semiscarce scenario, Semiample scenario, and Ample scenario. For the Scarce scenario, a multiple stepwise regression model was trained using 85 cases (80 prostate, 5 prostate-plus-lymph-node). The proposed workflow started with evaluating the feature novelty of new cases against 5 training prostate-plus-lymph-node cases using leverage statistic. The case database was composed of a 5-case dose atlas. Case-based dose prediction was compared against the regression model prediction using sum of squared residual. Mean sum of squared residual of case-based and regression predictions for the bladder of 13 identified outliers were 0.174 ± 0.166 and 0.459 ± 0.508, respectively (P = .0326). For the rectum, the respective mean sum of squared residuals were 0.103 ± 0.120 and 0.150 ± 0.171 for case-based and regression prediction (P = .1972). By retaining novel cases, under the Ample scenario, significant statistical improvement was observed over the Scarce scenario (P = .0398) for the bladder model. We expect that the incorporation of case-based reasoning that judiciously applies appropriate predictive models could improve overall prediction accuracy and robustness in clinical practice.
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    Postoperative statin use and risk of biochemical recurrence following radical prostatectomy: results from the Shared Equal Access Regional Cancer Hospital (SEARCH) database.
    (BJU Int, 2014-11) Allott, EH; Howard, LE; Cooperberg, MR; Kane, CJ; Aronson, WJ; Terris, MK; Amling, CL; Freedland, SJ
    OBJECTIVE: To investigate the effect of statin use after radical prostatectomy (RP) on biochemical recurrence (BCR) in patients with prostate cancer who never received statins before RP. PATIENTS AND METHODS: We conducted a retrospective analysis of 1146 RP patients within the Shared Equal Access Regional Cancer Hospital (SEARCH) database. Multivariable Cox proportional hazards analyses were used to examine differences in risk of BCR between post-RP statin users vs nonusers. To account for varying start dates and duration of statin use during follow-up, post-RP statin use was treated as a time-dependent variable. In a secondary analysis, models were stratified by race to examine the association of post-RP statin use with BCR among black and non-black men. RESULTS: After adjusting for clinical and pathological characteristics, post-RP statin use was significantly associated with 36% reduced risk of BCR (hazard ratio [HR] 0.64, 95% confidence interval [CI] 0.47-0.87; P = 0.004). Post-RP statin use remained associated with reduced risk of BCR after adjusting for preoperative serum cholesterol levels. In secondary analysis, after stratification by race, this protective association was significant in non-black (HR 0.49, 95% CI 0.32-0.75; P = 0.001) but not black men (HR 0.82, 95% CI 0.53-1.28; P = 0.384). CONCLUSION: In this retrospective cohort of men undergoing RP, post-RP statin use was significantly associated with reduced risk of BCR. Whether the association between post-RP statin use and BCR differs by race requires further study. Given these findings, coupled with other studies suggesting that statins may reduce risk of advanced prostate cancer, randomised controlled trials are warranted to formally test the hypothesis that statins slow prostate cancer progression.
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    Videos of Sipuleucel-T Programmed T Cells Lysing Cells That Express Prostate Cancer Target Antigens.
    (Journal of the National Cancer Institute, 2021-02-25) Kibel, Adam S; Inman, Brant A; Pachynski, Russell K; Vu, Tuyen; Sheikh, Nadeem A; Petrylak, Daniel P
    Sipuleucel-T, an autologous cellular immunotherapy, was approved to treat metastatic castration-resistant prostate cancer in 2010 in the United States. Treatment with sipuleucel-T primes the immune system to target prostate acid phosphatase (PAP), which is expressed by prostate cancer cells, potentially leading to lysis of cancer cell. Expanding upon previously reported indirect evidence of cell killing with sipuleucel-T treatment, we sought to provide direct evidence of cell lysis through visualization. We used advanced video technology and available samples of peripheral blood mononuclear cells from subjects enrolled in the STAMP trial (NCT01487863). Isolated CD8+ T cells were used as effector cells and co-cultured with autologous monocytes pulsed with control or target antigens. Differentially stained effector and target cells were then video-recorded during co-culture. Here, we present video recordings and analyses of T cells from sipuleucel-T-treated subjects showing-for the first time-direct lysis of cells that express prostate cancer target antigens, PAP or prostate-specific antigen.