In the 1940s Charles Huggins reported remarkable palliative benefits following surgical castration in men with advanced prostate cancer, and since then the androgen receptor (AR) has remained the ...main therapeutic target in this disease. Over the past couple of decades, our understanding of AR-signaling biology has dramatically improved, and it has become apparent that the AR can modulate a number of other well-described oncogenic signaling pathways. Not surprisingly, mounting preclinical and epidemiologic data now supports a role for AR-signaling in promoting the growth and progression of several cancers other than prostate, and early phase clinical trials have documented preliminary signs of efficacy when AR-signaling inhibitors are used in several of these malignancies. In this article, we provide an overview of the evidence supporting the use of AR-directed therapies in prostate as well as other cancers, with an emphasis on the rationale for targeting AR-signaling across tumor types.
Diet may play an essential role in the aetiology of bladder cancer (BC). Vitamin D is involved in various biological functions which have the potential to prevent BC development. Besides, vitamin D ...also influences the uptake of calcium and phosphorus, thereby possibly indirectly influencing the risk of BC. The aim of the present study was to investigate the relation between vitamin D intake and BC risk.
Individual dietary data were pooled from ten cohort studies. Food item intake was converted to daily intakes of vitamin D, calcium and phosphorus. Pooled multivariate hazard ratios (HRs), with corresponding 95% confidence intervals (CIs) were obtained using Cox-regression models. Analyses were adjusted for gender, age and smoking status (Model 1), and additionally for the food groups fruit, vegetables and meat (Model 2). Dose–response relationships (Model 1) were examined using a nonparametric test for trend.
In total, 1994 cases and 518,002 non-cases were included in the analyses. The present study showed no significant associations between individual nutrient intake and BC risk. A significant decreased BC risk was observed for high vitamin D intake with moderate calcium and low phosphorus intake (Model 2: HRhigh vitD, mod Ca, low P: 0.77, 95% CI: 0.59–1.00). No significant dose–response analyses were observed.
The present study showed a decreased BC risk for high dietary vitamin D intake in combination with low calcium intake and moderate phosphorus intake. The study highlights the importance of examining the effect of a nutrient in combination with complementary nutrients for risk assessment. Future research should focus on nutrients in a wider context and in nutritional patterns.
African swine fever epidemic in China Zhou, Lin; Yu, Evan Y. W.; Wang, Shujin ...
Veterinary record,
06/2019, Letnik:
184, Številka:
23
Journal Article
Recenzirano
Infection with ASF virus (ASFV) is reported to result in almost 100 per cent mortality in pigs.1 Recently, an outbreak of ASFV in China caused serious concern for the government.2,3 We describe this ...epidemic of ASF in China between August 2018 and January 2019, based on the public data released by the Ministry of Agriculture and Rural Affairs of China (MARA), to add to the body of evidence on ASF outbreaks (Table 1, supplementary data – available online at https://veterinaryrecord.bmj.com/content/184/23).SP110.1136/vr.l4026.supp1 Supplementary data According to the data, 117 ASF cases occurred in China from August 2018 to January 2019. ...10,398 of 268,698 pigs infected with ASFV died, the remainder were culled. Since the initial occurrence in Liaoning province in August 2018, ASFV has spread across 25 provinces in China (Fig 1). The control of ASF in China, where a lot of individual farmers and pig/pork movements exist, is a long-term challenge and needs a joint effort at home and abroad.4References 1 Galindo I, Alonso C. African swine fever virus: a review.
Targeting prostate-specific membrane antigen (PSMA) has important therapeutic ramifications, more recently including immune oncology. Data were recently presented on the preclinical efficacy of a ...half-life extended bispecific T-cell engager, AMG 160, which binds PSMA and CD3 to induce T-cell-driven cytolytic activity against prostate cancer.
.
Multi-institution retrospective cohort study showed that patients with ECOG PS ≥2 (compared to ECOG PS 0–1) had comparable overall response rate but worse overall survival with treatment with immune ...checkpoint inhibitor as first line therapy, while treatment initiation in the last 30 days of life was associated with increased odds of hospital death.
PARP inhibitors (PARPi) are promising in
-altered prostate cancer. Data were presented on PARPi efficacy in prostate cancers with alterations in other DNA damage repair genes which suggest low ...response rates in
-altered tumors and promising results in
, and
-altered tumors.
.
Germline testing (GT) is a central feature of prostate cancer (PCA) treatment, management, and hereditary cancer assessment. Critical needs include optimized multigene testing strategies that ...incorporate evolving genetic data, consistency in GT indications and management, and alternate genetic evaluation models that address the rising demand for genetic services.
A multidisciplinary consensus conference that included experts, stakeholders, and national organization leaders was convened in response to current practice challenges and to develop a genetic implementation framework. Evidence review informed questions using the modified Delphi model. The final framework included criteria with strong (> 75%) agreement (Recommend) or moderate (50% to 74%) agreement (Consider).
Large germline panels and somatic testing were recommended for metastatic PCA. Reflex testing-initial testing of priority genes followed by expanded testing-was suggested for multiple scenarios. Metastatic disease or family history suggestive of hereditary PCA was recommended for GT. Additional family history and pathologic criteria garnered moderate consensus. Priority genes to test for metastatic disease treatment included
and mismatch repair genes, with broader testing, such as
, for clinical trial eligibility.
was recommended for active surveillance discussions. Screening starting at age 40 years or 10 years before the youngest PCA diagnosis in a family was recommended for
carriers, with consideration in
, and mismatch repair carriers. Collaborative (point-of-care) evaluation models between health care and genetic providers was endorsed to address the genetic counseling shortage. The genetic evaluation framework included optimal pretest informed consent, post-test discussion, cascade testing, and technology-based approaches.
This multidisciplinary, consensus-driven PCA genetic implementation framework provides novel guidance to clinicians and patients tailored to the precision era. Multiple research, education, and policy needs remain of importance.
Opinion statement
Despite significant advances and the approval of immune checkpoint inhibitors, metastatic urothelial carcinoma (mUC) is still very hard to treat and has poor outcomes. Deeper ...understanding of the molecular underpinnings of mUC has identified potential biomarkers, biologic drivers, and relevant therapy targets. However, targeted therapies in mUC have had significant challenges due to molecular heterogeneity, clonal evolution, and genomic instability, and have not improved outcomes so far. Despite that, recent technological developments, clinical utilization of molecular biology, and discovery of new agents with preclinical and early clinical activity have signaled a new age of experimental therapeutics in mUC. The more frequent use of next-generation sequencing of tumor tissue and cell-free circulating tumor DNA, combined with novel agents tested in clinical trials, provides promise. There is a plethora of agents being tested in mUC, including inhibitors of receptors and signaling pathways (e.g., fibroblast growth factor receptor, human epidermal growth factor receptor, phosphatidylinositol 3-kinase/AKT/mTOR pathway), angiogenesis (e.g., vascular endothelial growth factor and its receptors), poly (ADP-ribose) polymerase (PARP) inhibitors, immuno-oncology agents, cytotoxic agents (e.g., chemotherapy, antibody drug conjugates), and epigenetic modulators, among others. Two agents, enfortumab-vedotin (antibody drug conjugate) and erdafitinib (fibroblast growth factor receptor inhibitor), have breakthrough designation by the FDA, but are not approved as of March 2019. Novel combinations with various modalities and optimal sequencing of active therapies are being investigated in clinical trials. More sophisticated patient selection, discovery and prospective validation of predictive (and prognostic) biomarkers with clinical utility, and relevant clinical trial designs are important parameters in that context. Based on the above, there is high potential for targeted therapies to be added in the growing armamentarium of mUC, and possibly complement chemotherapy and immuno-oncology agents.
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