Mechanistic Insights into the Link between Obesity and Prostate Cancer.

Obesity is a pandemic of increasing worldwide prevalence. There is evidence of an association between obesity and the risk of prostate cancer from observational studies, and different biologic mechanisms have been proposed. The chronic low-level inflammation within the adipose tissue in obesity results in oxidative stress, activation of inflammatory cytokines, deregulation of adipokines signaling, and increased circulating levels of insulin and insulin-like growth factors (IGF). These mechanisms may be involved in epithelial to mesenchymal transformation into a malignant phenotype that promotes invasiveness, aggressiveness, and metastatic potential of prostate cancer. A thorough understanding of these mechanisms may be valuable in the development of effective prostate cancer prevention strategies and treatments. This review provides an overview of these mechanisms.

A phase 2 trial of consolidation pembrolizumab following concurrent chemoradiation for patients with unresectable stage III non-small cell lung cancer: Hoosier Cancer Research Network LUN 14-179.

BACKGROUND: Five-year overall survival (OS) for patients with unresectable stage III non-small cell lung cancer (NSCLC) is poor. Until recently, a standard of care was concurrent chemoradiation alone. Patients with metastatic NSCLC treated with anti-programmed death 1 antibodies have demonstrated improved OS. This trial evaluated pembrolizumab as consolidation therapy after concurrent chemoradiation in patients with unresectable stage III disease. METHODS: Patients with unresectable stage III NSCLC received concurrent chemoradiation with cisplatin and etoposide, cisplatin and pemetrexed, or carboplatin and paclitaxel and 59.4 to 66.6 Gy of radiation. Patients with nonprogression of disease were enrolled and received pembrolizumab (200 mg intravenously every 3 weeks for up to 12 months). The primary endpoint was the time to metastatic disease or death (TMDD). Secondary endpoints included progression-free survival (PFS) and OS. RESULTS: The median follow-up for 93 patients (92 for efficacy) was 32.2 months (range, 1.2-46.6 months). The median TMDD was 30.7 months (95% confidence interval [CI], 18.7 months to not reached), which was significantly longer than the historical control of 12 months (P < .0001). The median PFS was 18.7 months (95% CI, 12.4-33.8 months), and the median OS was 35.8 months (95% CI, 24.2 months to not reached). The 1-, 2-, and 3-year OS estimates were 81.2%, 62.0%, and 48.5%, respectively. Forty patients (43.5%) completed 12 months of treatment (median number of cycles, 13.5). Symptomatic pneumonitis (grade 2 or higher) was noted in 16 patients (17.2%); these cases included 4 grade 3 events (4.3%), 1 grade 4 event (1.1%), and 1 grade 5 event (1.1%). CONCLUSIONS: Consolidation pembrolizumab after concurrent chemoradiation improves TMDD, PFS, and OS in comparison with historical controls of chemoradiation alone. Rates of grade 3 to 5 pneumonitis were similar to those reported with chemoradiation alone.

Phase II trial of docetaxel, bevacizumab, lenalidomide and prednisone in patients with metastatic castration-resistant prostate cancer.

OBJECTIVE: To determine the safety and clinical efficacy of two anti-angiogenic agents, bevacizumab and lenalidomide, with docetaxel and prednisone. PATIENTS AND METHODS: Eligible patients with metastatic castration-resistant prostate cancer enrolled in this open-label, phase II study of lenalidomide with bevacizumab (15 mg/kg), docetaxel (75 mg/m(2) ) and prednisone (10 mg daily). Docetaxel and bevacizumab were administered on day 1 of a 3-week treatment cycle. To establish safety, lenalidomide dosing in this combination was escalated in a conventional 3 + 3 design (15, 20 and 25 mg daily for 2 weeks followed by 1 week off). Patients received supportive measures including prophylactic pegfilgrastim and enoxaparin. The primary endpoints were safety and clinical efficacy. RESULTS: A total of 63 patients enrolled in this trial. Toxicities were manageable with most common adverse events (AEs) being haematological, and were ascertained by weekly blood counts. Twenty-nine patients (46%) had grade 4 neutropenia, 20 (32%) had grade 3 anaemia and seven (11%) had grade 3 thrombocytopenia. Despite frequent neutropenia, serious infections were rare. Other common non-haematological grade 3 AEs included fatigue (10%) and diarrhoea (10%). Grade 2 AEs in >10% of patients included anorexia, weight loss, constipation, osteonecrosis of the jaw, rash and dyspnoea. Of 61 evaluable patients, 57 (93%), 55 (90%) and 33 (54%) had PSA declines of >30, >50 and >90%, respectively. Of the 29 evaluable patients, 24 (86%) had a confirmed radiographic partial response. The median times to progression and overall survival were 18.2 and 24.6 months, respectively. CONCLUSIONS: With appropriate supportive measures, combination angiogenesis inhibition can be safely administered and potentially provide clinical benefit. These hypothesis-generating data would require randomized trials to confirm the findings.

Racial disparities in the association between variants on 8q24 and prostate cancer: a systematic review and meta-analysis.

Recent studies implicate single nucleotide polymorphisms (SNPs) within the 8q24 region as a risk factor for prostate cancer (PCa). New developments suggest that 8q24 encodes regulators of the nearby MYC gene, a known oncogene. In order to better understand the implications of SNPs in this region, we performed meta-analyses, stratified by race, of seven SNPs and one microsatellite marker previously identified as risk loci on the 8q24 region of the genome. In addition, we reviewed the literature examining the possible associations between these polymorphisms and clinicopathological features of PCa. The results of the meta-analyses indicate that rs6983267, rs1447295, rs6983561, rs7837688, rs16901979, and DG8S737 are significantly associated with a higher risk for PCa for at least one race, whereas the variants rs13254738 and rs7000448 are not. The degree of association and frequency of the causative allele varied among men of different races. Though several studies have demonstrated an association between certain 8q24 SNPs and clinicopathological features of the disease, review of this topic revealed conflicting results.

The preferred learning style among residents and faculty members of an internal medicine residency program.

OBJECTIVE: To determine the preferred learning style, as defined by David Kolb, and predictors of the different learning styles among residents and faculty members at an internal medicine residency program. DESIGN/SETTING: A cross sectional study of internal medicine residents and faculty members at Morehouse School of Medicine was performed using the Kolb Learning Style Inventory (LSI) version 3.1. MEASUREMENTS: The Kolb LSI is a questionnaire of 12 sentences, each with four phrases for sentence completion that are to be ranked according to how they apply to the subject. RESULTS: Forty-two out of 59 questionnaires that were given out to residents and attending physicians were properly completed and returned. Assimilating style was the predominant learning style among residents (42%) and attending physicians (55%). There was no significant association between age, gender or medical education status, and learning styles. CONCLUSIONS: The understanding of residents' learning styles may facilitate instructional rapport between residents and attending physicians, thereby improving residents' academic performance.

Angiogenesis inhibitors in the treatment of prostate cancer.

Prostate cancer is the most common cancer in men in the United States and is the second most common cause of death. While treatment options in early stage disease are curative in intent, treatment of metastatic prostate cancer remains challenging. Although, several new and promising treatment options exploiting novel targets have permeated the therapeutic landscape in recent years, another viable target for therapy is tumor angiogenesis. Many antiangiogenic agents are under development and some are currently under investigation in clinical trials.

Impact of peripheral arterial disease on functional limitation in congestive heart failure: results from the national health and nutrition examination survey (1999-2004).

Background. Peripheral arterial disease (PAD) often coexists with congestive heart failure (CHF) and can be masked by symptoms of CHF such as functional limitation (FL), a common manifestation for both. Therefore, we sought to estimate the prevalence of PAD and its independent association with FL in CHF. Methods. We conducted a cross-sectional study on National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2004 to quantify weighted prevalence of CHF and PAD. Study cohort consisted of 7513, with ankle brachial index (ABI) measurements at baseline. Independent association of PAD (ABI ≤ 0.9) with FL in CHF was determined with multivariate logistic regression (MVLR). Results. Overall weighted PAD prevalence was 5.2%. CHF was present in 305 participants, and the weighted prevalence of PAD in this subgroup was 19.2%. When compared, participants with CHF and PAD were more likely to be older (P < 0.001), hypertensive (P = 0.005) and hypercholesterolemic (P = 0.013) than participants with CHF alone. MVLR showed that PAD (adjusted OR = 5.15; 95% CI: 2.2, 12.05: P < 0.05) and arthritis (adjusted OR = 2.36; 95% CI: 1.10, 5.06: P < 0.05) were independently associated with FL in CHF. Conclusion. Independent association of PAD with FL suggests the need for reinforced screening for PAD in individuals with CHF.