Query: prostate cancer sythesis

title: M2 macrophages and regulatory T cells in lethal prostate cancer
abstract: Prostate cancer (PCa) is one of the most frequently diagnosed cancers in the world. Emerging evidence suggests that inflammatory cells such as M2 macrophages and regulatory T cells (Tregs) can contribute to cancer progression by suppressing the anti tumor immune response. This study investigated the number of CD163 positive M2 macrophages in PCa tissue. It also investigated the correlation and interaction of M2 macrophages and Tregs.

title: The anticancer potential of metformin on prostate cancer
abstract: BackgroundProstate cancer (PCa) is characterized as the most frequent type of cancer in males. Recent research has suggested patients who have diabetes mellitus taking metformin (MF) have a lower risk of PCa. MF has antineoplastic effects such as adenosine monophosphate activated protein kinase (AMPK) dependent and independent mechanisms, suppression of androgen signaling pathway, and alterations of insulin like growth factor 1 (IGF 1) signaling pathways that cause the growth and proliferation of PCa. Based on epidemiological factors, patients with diabetes mellitus may have a protective effect on PCa.MethodsA literature search on MEDLINE(r) was conducted using a combined query of "prostate cancer" and "metformin" to yield publications unveiling the mechanisms of action, biological effects, epidemiological evidence, and research advances of MF with respect to PCa.ResultsEvidence has shown that MF has multiple antineoplastic effects through AMPK dependent and independent mechanisms, the alteration of IGF 1 signaling pathways, suppression of the androgen receptor pathway, inhibition of the mTOR pathway, and lipogenesis. Conduction of meta analysis suggests mortality benefit to patients who exhibit PCa when taking MF. Clinical trials have shown evidence, demonstrating MF to improving significantly.ConclusionsHerewith we review the literature regarding the numerous mechanisms of action of MF on PCa in order to decrease or repress the growth, proliferation, and differentiation of PCa cells. We analyze the molecular impacts of MF as well as adjunct therapies such as androgen deprivation therapy, aspirin, statin, or chemotherapy, proposing that MF may have a future role in the treatment protocol of PCa whether as a monotherapy or in combination with other drugs.

title: Androgen targeted therapy in men with prostate cancer: evolving practice and future considerations
abstract: BackgroundAndrogen deprivation therapy (ADT) is foundational in the management of advanced prostate cancer (PCa) and has benefitted from a recent explosion in scientific advances. These include approval of new therapies that suppress testosterone (T) levels or inactivate its function, improvements in diagnostic and assay technologies, identification of lower therapeutic targets for T, discovery of the relevance of germline genetic mutations and identification of the benefits of sequential and combination therapies.MethodsThis review discusses the clinical profiles of the most up to date options for ADT, best practices for managing patients with advanced PCa and future directions in therapy.Results and conclusionsModern assay technologies reveal that bilateral orchiectomy results in a serum T level of approximately 15 ng/dL as compared to the historical definition of castration of T 50 ng/dL. Evidence shows that lowering T levels to <20 ng/dL improves patient survival and delays disease progression. Routine monitoring of T in addition to prostate specific antigen throughout treatment is important to ensure continuing efficacy of T suppression. New drugs that inhibit androgen signaling in combination with traditional ADT suppress T activity to near zero and have significantly improved patient survival. When personalizing ADT regimens physicians should consider a number of factors including initiation and duration of ADT, monitoring of T levels and PSA, the possibility of switching monotherapies if a patient does not achieve adequate T suppression, and consideration of intermittent vs. continuous ADT according to patients' lifestyles, comorbidities, risk factors and tolerance to treatment.

title: Estrogen receptor signaling in prostate cancer: Implications for carcinogenesis and tumor progression
abstract: The androgen receptor (AR) is the classical target for prostate cancer prevention and treatment, but more recently estrogens and their receptors have also been implicated in prostate cancer development and tumor progression.

title: Intraductal/ductal histology and lymphovascular invasion are associated with germline DNA repair gene mutations in prostate cancer
abstract: Germline mutations in genes mediating DNA repair are common in men with recurrent and advanced prostate cancer, and their presence may alter prognosis and management. We aimed to define pathological and clinical characteristics associated with germline DNA repair gene mutations, to facilitate selection of patients for germline testing.

title: 68Ga PSMA PET/CT vs. mpMRI for locoregional prostate cancer staging: correlation with final histopathology
abstract: BackgroundProstate specific membrane antigen (PSMA) positron emission tomography (PET) can be used to locate lesions based on PSMA avidity, however guidelines on its use are limited by its infancy. We aimed to compare multiparametric magnetic resonance imaging (mpMRI) and PSMA PET/CT to prostatectomy histopathology.MethodsWe conducted a chart review from February 2015 to January 2017 of 50 male patients staged for prostate cancer using PSMA PET/CT and mpMRI who then underwent radical prostatectomy. Pre operative PSMA PET/CT and mpMRI were paired with corresponding histopathology. Correlations, sensitivity, and specificity were used for comparisons. total of 81 lesions were confirmed by histopathology. Fifty index lesions were detected by histopathology, all of which were detected by PSMA PET/CT (100% detection) and 47 by mpMRI (94% detection) Thirty one histologically confirmed secondary lesions were detected, 29 of which were detected by PSMA PET/CT (93.5% detection) and 16 by mpMRI (51.6% detection) PSMA had better sensitivity for index lesion localization than mpMRI (81.1 vs. 64.8% Specificity was similar for PSMA PET/CT and mpMRI (84.6 vs. 82.7%.SUVmax of index lesions ranged from 2.9 to 39.6 (M 9.27 6.41) Index lesion SUVmax was positively correlated with PSA (rho 0.48, p 0.001) and ISUP grade (rho 0.51, p 0.001).ConclusionsPSMA PET/CT provided superior detection of prostate cancer lesions with better sensitivity than mpMRI. PSMA PET/CT can be used to enhance locoregional mpMRI to provide improved detection and characterization of lesions.

title: Movember GAP1 PDX project: An international collection of serially transplantable prostate cancer patient derived xenograft (PDX) models
abstract: While it has been challenging to establish prostate cancer patient derived xenografts (PDXs) with a take rate of 10 40% and long latency time, multiple groups throughout the world have developed methods for the successful establishment of serially transplantable human prostate cancer PDXs using a variety of immune deficient mice. In 2014, the Movember Foundation launched a Global Action Plan 1 (GAP1) project to support an international collaborative prostate cancer PDX program involving eleven groups. Between these Movember consortium members, a total of 98 authenticated human prostate cancer PDXs were available for characterization. Eighty three of these were derived directly from patient material, and 15 were derived as variants of patient derived material via serial passage in androgen deprived hosts. A major goal of the Movember GAP1 PDX project was to provide the prostate cancer research community with a summary of both the basic characteristics of the 98 available authenticated serially transplantable human prostate cancer PDX models and the appropriate contact information for collaborations. Herein, we report a summary of these PDX models.

title: Compositional differences in gastrointestinal microbiota in prostate cancer patients treated with androgen axis targeted therapies
abstract: BackgroundIt is well known that the gastrointestinal (GI) microbiota can influence the metabolism, pharmacokinetics, and toxicity of cancer therapies. Conversely, the effect of cancer treatments on the composition of the GI microbiota is poorly understood. We hypothesized that oral androgen receptor axis targeted therapies (ATT) including bicalutamide, enzalutamide, and abiraterone acetate, may be associated with compositional differences in the GI microbiota.MethodsWe profiled the fecal microbiota in a cross sectional study of 30 patients that included healthy male volunteers and men with different clinical states of prostate cancer (i.e. localized, biochemically recurrent, and metastatic disease) using 16S rDNA amplicon sequencing. Functional inference of identified taxa was performed using PICRUSt.ResultsWe report a significant difference in alpha diversity in GI microbiota among men with versus without a prostate cancer diagnosis. Further analysis identified significant compositional differences in the GI microbiota of men taking ATT, including a greater abundance of species previously linked to response to anti PD 1 immunotherapy such as Akkermansia muciniphila and Ruminococcaceae spp. In functional analyses, we found an enriched representation of bacterial gene pathways involved in steroid biosynthesis and steroid hormone biosynthesis in the fecal microbiota of men taking oral ATT.ConclusionsThere are measurable differences in the GI microbiota of men receiving oral ATT. We speculate that oral hormonal therapies for prostate cancer may alter the GI microbiota, influence clinical responses to ATT, and/or potentially modulate the antitumor effects of future therapies including immunotherapy. Given our findings, larger, longitudinal studies are warranted.

title: GOLM1 promotes prostate cancer progression through activating PI3K AKT mTOR signaling
abstract: Prostate cancer (PCa) is the most commonly diagnosed cancer in men. Various molecular mechanisms account for PCa progression and elucidation of these mechanisms is key for selection of optimal therapies and improvement of patient outcome. Golgi membrane protein 1 (GOLM1) has been identified as a novel biomarker for PCa, but its biological functions and molecular mechanisms remain poorly understood.

title: Annual Report to the Nation on the status of cancer, 1975 2010, featuring prevalence of comorbidity and impact on survival among persons with lung, colorectal, breast, or prostate cancer
abstract: The American Cancer Society (ACS) the Centers for Disease Control and Prevention (CDC) the National Cancer Institute (NCI) and the North American Association of Central Cancer Registries (NAACCR) collaborate annually to provide updates on cancer incidence and death rates and trends in these outcomes for the United States. This year's report includes the prevalence of comorbidity at the time of first cancer diagnosis among patients with lung, colorectal, breast, or prostate cancer and survival among cancer patients based on comorbidity level.