The contribution of dietary and plasma folate and cobalamin to levels of angiopoietin-1, angiopoietin-2 and Tie-2 receptors depend on vascular endothelial growth factor status of primary breast cancer patients.

The aim of this study was to determine the association of dietary folate and cobalamin with plasma levels of Angiopoietins (ANG), vascular endothelial growth factor-C (VEGF-C) and tyrosine kinase receptor-2 (Tie-2) of primary breast cancer patients. Women (n = 177), aged 30 to 75 years diagnosed with breast cancer were recruited from an ongoing case series study. Dietary intake of nutrients was estimated by using a validated food frequency questionnaire. Enzyme-linked immunosorbent assay was applied to measure biomarkers. MCF-7 cell cultures were supplemented with folic acid (0-40 µM) for 24 h to measure cell viability and fold change of expression by the real-time reverse transcriptase-polymerase chain reaction. Structural equation modeling was applied to analyze the structural relationships between the measured variables of nutrients and Angiopoietins. Dietary intake of folate and cobalamin showed a significant inverse correlation with plasma ANG-1 and ANG-2 (P < 0.05), particularly in subjects with estrogen-receptor positive tumors or low plasma VEGF-C. Plasma folate was positively associated with the ratio of ANG-1/ANG-2 (P < 0.05). Residual intake levels of total cobalamin were inversely associated with plasma ANG-1 when plasma stratum of VEGF-C was high (P < 0.05). Structural equation modeling identified a significant inverse contribution of folate profiles on the latent variable of Angiopoietins (coefficient ß = -0.99, P < 0.05). Folic acid treatment resulted in dose-dependent down-regulations on ANGPT1 and ANGPT1/ANGPT2 ratio but VEGF and ANGPT2/VEGF were upregulated at folic acid >20 µM. Studying the contributing role of dietary folate to pro-angiogenic biomarkers in breast cancer patients can infer the preventive role of folate in the ANGs/VEGF-C-dependent cascade of tumor metastasis. By contrast, high concentrations of folic acid in vitro supported VEGF-C-dependent ANGPT2 overexpression might potentiate micro-lymphatic vessel development to support malignant cell dissemination.

Prognostic value of tumor-infiltrating mast cells in outcome of patients with esophagus squamous cell carcinoma.

BACKGROUND: Squamous cell carcinoma (SCC) of the esophagus is one of the most common malignancies of the gastrointestinal tract and carries poor prognosis. The role of mast cell density (MCD) in the prognosis of most human tumors is partly known, and there is a growing body of studies addressing it. However, the prognostic value of MCD has not been investigated in esophageal SCC, and thus, it was the subject during this study. METHODS: In this study, 78 patients with esophageal SCC in pT = 3 were selected, their MCD was evaluated with toluidine blue staining, and the relationship with survival rate was analyzed. Patients were compared in identical groups of lymph node involvement and post-surgery complementary therapy. RESULTS: Survival rate was significantly decreased in patients with high MCD based on Kaplan-Meier analysis (P < 0.001). This relationship was also found in groups with similar lymph node involvement and post-surgery therapies. CONCLUSIONS: The results of the current study showed that high MCD in the invasive edge of tumor is related to tumor progression and decreased survival rate following surgery.