"THE VOCAL BEHAVIOUR OF MALE EUROPEAN TREEFROGS (HYLA ARBOREA): IMPLICATIONS FOR INTER- AND INTRASEXUAL SELECTION" published on 01 Jan 2002 by Brill.

Obese breast cancer patients have worse prognosis than normal weight patients, but the level at which obesity is prognostically unfavorable is unclear. This retrospective analysis was performed using data from the SUCCESS A trial, in which 3754 patients with high-risk early breast cancer were randomized to anthracycline- and taxane-based chemotherapy with or without gemcitabine. Patients were classified as underweight/normal weight (body mass index (BMI) < 25.0), overweight (BMI 25.0–29.9), slightly obese (BMI 30.0–34.9), moderately obese (BMI 35.0–39.9) and severely obese (BMI ≥ 40.0), and the effect of BMI on disease-free survival (DFS) and overall survival (OS) was evaluated (median follow-up 65 months). In addition, subgroup analyses were conducted to assess the effect of BMI in luminal A-like, luminal B-like, HER2 (human epidermal growth factor 2)-positive and triple-negative tumors. Multivariate analyses revealed an independent prognostic effect of BMI on DFS (p = 0.001) and OS (p = 0.005). Compared with underweight/normal weight patients, severely obese patients had worse DFS (hazard ratio (HR) 2.70, 95 % confidence interval (CI) 1.71–4.28, p < 0.001) and OS (HR 2.79, 95 % CI 1.63–4.77, p < 0.001), while moderately obese, slightly obese and overweight patients did not differ from underweight/normal weight patients with regard to DFS or OS. Subgroup analyses showed a similar significant effect of BMI on DFS and OS in patients with triple-negative breast cancer (TNBC), but not in patients with other tumor subtypes. Severe obesity (BMI ≥ 40) significantly worsens prognosis in early breast cancer patients, particularly for triple-negative tumors. Clinicaltrials.gov NCT02181101 . Registered September 2005.

Ovarian cancer is mostly associated with pathologically regulated permeability of peritoneal vessels, leading to ascites. Here, we investigated the molecular regulation of endothelial permeability by the vascular endothelial growth factor (VEGF) and both tight and adherens junction proteins (VE-cadherin and claudin 5) with regards to the tumor biology of different ovarian cancer types. Serum and ascites samples before and after surgery, as well as peritoneal biopsies of 68 ovarian cancer patients and 20 healthy controls were collected. In serum and ascites VEGF protein was measured by ELISA. In peritoneal biopsies co-localization of VE-cadherin and claudin 5 was investigated using immunohistochemical dual staining. In addition, the gene expression of VE-cadherin and claudin 5 was quantified by Real-time PCR. Differences in VEGF levels, VE-cadherin and claudin 5 gene expression were analyzed in relation to various tumor characteristics (tumor stage, grading, histological subtypes, resection status after surgery) and then compared to controls. Furthermore, human primary ovarian cancer cells were co-cultured with human umbilical vein endothelial cells (HUVEC) and changes in VE-cadherin and claudin 5 were investigated after VEGF inhibition. VEGF was significantly increased in tumor patients in comparison to controls and accumulates in ascites. The highest VEGF levels were found in patients diagnosed with advanced tumor stages, with tumors of poor differentiation, or in the group of solid / cystic-solid tumors. Patients with residual tumor after operation showed significantly higher levels of VEGF both before and after surgery as compared to tumor-free resected patients. Results of an immunohistochemical double-staining experiment indicated co-localization of VE-cadherin and claudin 5 in the peritoneal vasculature. Compared to controls, expression of VE-cadherin and claudin 5 was significantly suppressed in peritoneal vessels of tumor patients, but there were no significant differences regarding VE-cadherin and claudin 5 expression in relation to different tumor characteristics. A significant positive correlation was found between VE-cadherin and claudin 5 expression. VEGF inhibition in vitro was associated with significant increase in VE-cadherin and claudin 5. Our results indicate that increased peritoneal permeability in ovarian cancer is due to down-regulation of adhesion proteins via tumor derived VEGF. Advanced ovarian cancer with aggressive tumor biology may be associated with early dysregulation of vascular permeability leading to ascites. These patients may benefit from therapeutic VEGF inhibition.