The regulatory T cells (Treg) play an important role in the tumor tolerance. The methods to regulate the Treg population in cancer-bearing hosts are limited currently. The effect of curcumin on inhibiting cancer has been recognized, but the mechanism remains elusive. This study tests a hypothesis that administration of curcumin down regulates Tregs in lung cancer (LC) patients. In this study, a group of LC patients was treated with curcumin. The peripheral Tregs and T helper (Th) 1 cells were analyzed by flow cytometry. The mechanism by which curcumin regulated the Tregs was observed by cell culture approaches. The results showed that the frequency of peripheral Treg was markedly higher in LC patients than that in healthy subjects, which was suppressed after treating with curcumin for 2 weeks. The peripheral Th1 cells were increased in LC patients after the curcumin therapy. The data of the in vitro experiments showed that curcumin converted the LC patient-isolated Tregs to Th1 cells via repressing the gene transcription of forkhead protein-3 and increasing the expression of interferon-γ. In conclusion, curcumin can convert LC patient-isolated Tregs to Th1 cells. The results suggest that curcumin may improve the antitumor immunity by regulating the tumor specific immune tolerance.

Background Expression of the stem cell marker octamer 4 (Oct-4) in various neoplasms has been previously reported, but very little is currently known about the potential function of Oct-4 in this setting. The purpose of this study was to assess the prognostic value of Oct-4 expression after surgery in primary non-small cell lung cancer (NSCLC) and investigate its possible molecular mechanism. Methods We measured Oct-4 expression in 113 NSCLC tissue samples and three cell lines by immunohistochemical staining and RT-PCR. The association of Oct-4 expression with demographic characteristics, proliferative marker Ki67, microvessel density (MVD), and expression of vascular endothelial growth factor (VEGF) were assessed. Results Oct-4 expression was detected in 90.3% of samples and was positively correlated with poor differentiation and adenocarcinoma histology, and Oct-4 mRNA was found in each cell lines detected. Overexpression of Oct-4 had a strong association with cells proliferation in all cases, MVD-negative, and VEGF-negative subsets. A Kaplan-Meier analysis showed that overexpression of Oct-4 was associated with shorter overall survival in all cases, adenocarcinoma, squamous cell carcinoma, MVD-negative, and VEGF-negative subsets. A multivariate analysis demonstrated that Oct-4 level in tumor tissue was an independent prognostic factor for overall survival in all cases, MVD-negative, and VEGF-negative subsets. Conclusion Our findings suggest that, even in the context of vulnerable MVD status and VEGF expression, overexpression of Oct-4 in tumor tissue represents a prognostic factor in primary NSCLC patients. Oct-4 may maintain NSCLC cells in a poorly differentiated state through a mechanism that depends on promoting cell proliferation.

BackgroundFibronectin (FN) is a high-molecular-weight glycoprotein component of the extracellular matrix involved in cell adhesion, migration, metastasis, proliferation and differentiation, as well as embryogenesis, wound healing, and blood coagulation. Considerable recent research has established that tumor expression of FN is closely associated with tumor formation and development as well as disease prognosis. However, the mechanisms underlying this relationship have remained unclear. The aim of this study was to investigate FN protein expression in esophageal squamous cell carcinoma (ESCC) and determine its potential prognostic relevance, while also elucidating the source and function of FN.MethodsWe conducted immunohistochemical analyses of protein expression in primary tumors of ESCC patients and analyzed their association with standard prognostic parameters and clinical outcomes. Expression of FN in two ESCC cell lines (Eca-109 and TE-1) was also examined by RT-PCR, immunofluorescence, and ELISA. ESCC cells were cultured in a microenvironment containing a high FN content, and changes in their morphology and migration ability were assessed by microscopy, wound-healing assays, and Transwell assays.ResultsFN expression in ESCC specimens was mainly detected in the tumor stroma, with very little FN detected in tumor cells. Stromal FN content in ESCC specimens was associated with lymphatic metastasis (P = 0.032) and prognosis. In this latter context, patients with high tumor stromal expression of FN showed worse overall survival (P = 0.002) and progression-free survival (P < 0.001) than those with low expression of FN. Interestingly, FN expression and secretion in ESCC cell lines (Eca-109 and TE-1) was found to be low, but these cells adopted a more migratory phenotype when cultured in vitro in a microenvironment containing high levels of FN.ConclusionsHigh FN expression in the stroma of ESCC tumors is closely associated with poor prognosis of patients. High stromal FN content facilitates tumor cell metastasis by promoting morphological changes and improving the motility and migratory ability of ESCC cells.

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