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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Androgen action in prostate and prostate cancer cells is dependent upon the androgen receptor (AR) protein that transcriptionally regulates the expression of androgen-dependent genes in the presence of a steroid ligand. Whereas the overall schema of androgen action mediated by this receptor protein appears to be relatively simple, androgen signaling is now known to be influenced by several other cell signal transduction pathways and here we review the evidence that the canonical Wnt signaling pathway also modulates androgen signaling at multiple levels. Wnt is a complex signaling pathway whose endpoint involves activation of transcription from LEF-1/TCF transcription factors and it is known to be involved in the development and progression of numerous human epithelial tumors including prostate cancer. beta-catenin protein, a particularly critical molecular component of canonical Wnt signaling is now known to promote androgen signaling through its ability to bind to the AR protein in a ligand-dependent fashion and to enhance the ability of liganded AR to activate transcription of androgen-regulated genes. Under certain conditions, glycogen synthase kinase-3beta (GSK-3beta), a protein serine/threonine kinase that regulates beta-catenin degradation within the Wnt signaling pathway, can also phosphorylate AR and suppress its ability to activate transcription. Finally, it was recently found that the human AR gene itself is a target of LEF-1/TCF-mediated transcription and that AR mRNA is highly upregulated by activation of Wnt signaling in prostate cancer cells. Paradoxically, Wnt activation also appears to stimulate Akt activity promoting an MDM-2-mediated degradation process that reduces AR protein levels in Wnt-stimulated prostate cancer cells. Collectively, this information indicates that the multifaceted nature of the interaction between the Wnt and the androgen signaling pathways likely has numerous consequences for the development, growth, and progression of prostate cancer.
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PMID:Multifaceted interaction between the androgen and Wnt signaling pathways and the implication for prostate cancer. 1674 72

Background: Patients undergoing surgery for prostate cancer who have adverse pathological findings experience high rates of recurrence. While there are data supporting adjuvant radiotherapy compared to a wait-and-watch strategy to reduce recurrence rates, there are no randomized controlled trials comparing adjuvant radiotherapy with the other standard of care, salvage radiotherapy (radiotherapy administered at the time of recurrence). Methods: We constructed a health state transition (Markov) model employing two-dimensional Monte Carlo simulation using a lifetime horizon to compare the quality-adjusted survival associated with postoperative strategies using adjuvant or salvage radiotherapy. Prior to analysis, we calibrated and validated our model using the results of previous randomized controlled trials. We considered clinically important oncological health states from immediately postoperative to prostate cancer-specific death, commonly described complications from prostate cancer treatment, and other causes of mortality. Transition probabilities and utilities for disease states were derived from a literature search of MEDLINE and expert consensus. Results: Salvage radiotherapy was associated with an increased quality-adjusted life expectancy (QALE) (58.3 months) as compared with adjuvant radiotherapy (53.7 months), a difference of 4.6 months (standard deviation 8.8). Salvage radiotherapy had higher QALE in 53% of hypothetical cohorts. There was a minimal difference in overall life expectancy (-0.1 months). Examining recurrence rates, our model showed validity when compared with available randomized controlled data. Conclusions: A salvage radiotherapy strategy appears to provide improved QALE for patients with adverse pathological findings following radical prostatectomy, compared with adjuvant radiotherapy. As these findings reflect, population averages, specific patient and tumor factors, and patient preferences remain central for individualized management.
MDM Policy Pract
PMID:Adjuvant Versus Salvage Radiotherapy for Patients With Adverse Pathological Findings Following Radical Prostatectomy: A Decision Analysis. 3028 22

Background. There is widespread agreement that both the length and quality of life matter when assessing new technologies and/or models of care in the treatment for cancer patients. Quality of life for partners/carers also matters, particularly for prostate cancer. Purpose. This systematic review aims to provide up-to-date utility values along the prostate cancer care continuum (i.e., from prescreening through to palliative care) for use where future trial-based or modelled economic evaluations cannot collect primary data from men and/or partners. Data Sources. A protocol was developed and registered on the international register of systematic reviews-PROSPERO. Databases searched included EBSCO Information Services (CINAHL, EconLit, Global Health, HEED, MEDLINE Complete, PsycINFO), Cochrane Database of Systematic Reviews, Web of Science, and Embase. Study Selection. Study selection terms included health-related quality of life, prostate cancer, and partners or carers. Data Extraction. The authors identified articles published between 2007 and 2016 that provided health state utility values, with statistical uncertainty, for men with or at risk of prostate cancer and/or their partner/carers. Data Synthesis and Results. Study quality and generalizability of utilities was evaluated and meta-analysis conducted against prespecified criteria. From 906 original articles, 29 recent primary studies met the inclusion/exclusion criteria. We tabulate all the utility values with uncertainty, along with considerable methodological detail and patient population characteristics. Limitations. Utility values pertaining to carers/partners were limited to one study. Conclusions. Studies varied in design, measurement instruments utilized, quality, and generalizability. There is sufficient qualitative and quantitative detail for the reported utility values to be readily incorporated into economic evaluations. More research is needed with carers/partners and with newly developing prostate cancer-specific quality of life tools.
MDM Policy Pract
PMID:A Systematic Review and Meta-Analysis of Prostate Cancer Utility Values of Patients and Partners Between 2007 and 2016. 3119 9

Objectives. To describe the development of our Patient Preferences for Prostate Cancer Care (PreProCare) tool to aid patient-centered treatment decision among localized prostate cancer patients. Methods. We incorporated patient and provider experiences to develop a patient preference elicitation tool using adaptive conjoint analysis. Our patient-centered approach used systematic literature review, semistructured patient interviews, and provider focus groups to determine the treatment attributes most important for decision making. The resulting computer-based PreProCare tool was pilot tested in a clinical setting. Results. A systematic review of 56 articles published between 1995 and 2015 yielded survival, cancer recurrence, side effects, and complications as attributes of treatment options. We conducted one-on-one interviews with 50 prostate cancer survivors and 5 focus groups of providers. Patients reported anxiety, depression, treatment specifics, and caregiver burden as important for decision making. Providers identified clinical characteristics as important attribute. Input from stakeholders' advisory group, physicians, and researchers helped finalize 15 attributes for our PreProCare preference assessment tool. Conclusion. The PreProCare tool was developed using a patient-centered approach and may be a feasible and acceptable preference clarification intervention for localized prostate cancer patients. The PreProCare tool may translate into higher participant engagement and self-efficacy, consistent with patients' personal values.
MDM Policy Pract
PMID:Patient-Centered Approach to Develop the Patient's Preferences for Prostate Cancer Care (PreProCare) Tool. 3125 48