Supplementation of patients receiving cisplatin chemotherapy with vitamin E decreases the incidence and severity of peripheral neurotoxicity.

Purpose: Tumor-induced platelet activation may cause the release of various cytokines, including CD40 ligand (CD40L). Activation of the CD40/CD40L pathway in human tumors may result in thrombin generation, which is known to be involved in angiogenesis. Thus, we investigated whether soluble (s)CD40L levels are increased in patients with lung cancer as a result of platelet and/or coagulation activation.Experimental Design: Citrated plasma samples were obtained from 120 patients with different stages and histotypes of lung cancer and 60 age-and sex-matched control subjects. sCD40L, sP-selectin (marker of platelet activation), prothrombin fragment 1 ؉ 2, and thrombin-antithrombin III complex levels (both markers of coagulative activation) were measured in all samples.Results: Patients with lung cancer had median sCD40L levels higher than in control subjects (0.46 versus 0.13 ng/ml; P < 0.0001), although correlation with the stage of disease was not evident. Nonetheless, sCD40L levels were significantly higher in squamous cancer compared with adenocarcinoma (0.75 versus 0.27 ng/ml; P < 0.05). Moreover, median sCD40L levels were higher in stage IV compared with nonmetastatic squamous lung cancer (1.02 versus 0.61 ng/ ml; P < 0.05). sCD40L levels significantly correlated with sP-selectin (P < 0.001), prothrombin fragment 1 ؉ 2 (P < 0.001), or thrombin-antithrombin III complex (P < 0.05) in squamous lung cancer, but only sP-selectin (P ‫؍‬ 0.011) was independently related to sCD40L.Conclusions: These findings indicate that elevated sCD40L levels can be preferentially found in patients with advanced squamous cancer and provide evidence that increased levels of this cytokine are associated to the occurrence of in vivo platelet activation.

The aim of this study is to evaluate the influence of germline vascular endothelial growth factor (VEGF) gene polymorphisms (VGPs) on the efficacy of the anti-VEGF antibody bevacizumab (Bev) in metastatic colorectal cancer (MCRC) patients

Measurement of soluble (s) P-selectin levels has been proposed as a diagnostic tool for monitoring the clinical course of human neoplasms. Thus, our study was aimed at analyzing the role of sP-selectin in association with clinicopathological variables in 181 patients with primary (n‫)941؍‬ or metastatic (n‫)23؍‬ colorectal cancer (CRC), 34 patients with benign diseases and 181 control subjects. The results obtained showed that sP-selectin levels were higher in patients with CRC compared either to patients with benign disease (p‫؍‬ 0.006) or controls (p‫؍‬ 0.003). No differences were observed between the latter and patients with benign diseases. Increased median sP-selectin levels were significantly associated with the presence of distant metastasis (68.2 ng/ml vs. 48.6 ng/ml, p‫؍‬ 0.002). Of interest, carcinoembryonic antigen (CEA) levels were independently associated to sP-selectin (regression coefficient‫؍‬ 0.28, p< 0.002). Cox's proportional hazards survival analysis of primary CRC patients demonstrated that beside the stage of disease sP-selectin levels had an independent prognostic role in predicting recurrent disease (HR‫؍‬ 2.22, p‫؍‬ 0.019) and mortality from CRC (HR‫؍‬ 3.44, p‫؍‬ 0.017). These results suggest that measurement of plasma sP-selectin might represent a prognostic indicator in the management of patients with CRC.

Objectives: A longitudinal study was designed to quantify tumor tissue content of vascular endothelial growth factor (VEGF) in patients with colorectal cancer (CRC) and to evaluate its prognostic value in respect to the relapse-free and overall survivals. Methods: Sixty-nine patients with CRC were followed from the time of diagnosis of primary tumor for at least 3 years after surgery. Quantitative evaluation of VEGF content in tissue was performed on whole protein extracts obtained from biopsies of histologically confirmed neoplastic tissues and corresponding mucosa, histologically confirmed as ‘normal’. Results: VEGF levels were higher in CRC tissues, median 141 pg/mg of protein (interquartile range 70–375), compared with corresponding normal mucosa, median 45 pg/mg of protein (interquartile range 22–78; p < 0.0001), and were associated with the stage of disease (p = 0.035) by multivariate analysis. Tumor VEGF content was higher in relapsing patients compared with those who remained disease free (p < 0.001) and was independently associated with relapse-free survival (p = 0.044). Cox’s proportional hazard survival analysis demonstrated that VEGF (p = 0.035) had an independent prognostic value in respect to overall survival. Conclusions: Elevated tumor VEGF content may discriminate between early and late stages of CRC and may be used as an independent prognostic parameter in the management of these patients.