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.

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.

In order to fully elucidate the association between serum fibrinogen and prognosis of esophageal cancer, we examined serum fibrinogen concentrations in 1512 patients who underwent esophagectomy by the Clauss method. The impact of fibrinogen on overall survival and disease-free survival was analyzed using the Kaplan-Meier method and Cox proportional hazard models. Hyperfibrinogenemia was significantly associated with older age, male gender, smoking, alcohol consumption, weight loss, advanced pathological T stage and lymph node metastasis. Patients with hyperfibrinogenemia exhibited poor OS (HR=1.20, 95%CI: 1.04-1.38, P=0.012) and DFS (HR=1.18, 95%CI: 1.03-1.35, P=0.019). Subgroup analysis further exhibited an significant association between hyperfibrinogenemia and poor OS (P<0.001), DFS (P<0.001) in esophageal squamous cell carcinoma (P<0.001) and early pathological stage (I-II) (P=0.001). Collectively, this study indicates that preoperative serum fibrinogen is an independent prognostic factor for survival in esophageal cancer.

ObjectiveMyasthenic crisis (MC) is considered the most severe adverse event in patients with myasthenia gravis. The present retrospective study was performed to evaluate the predictors of clinical outcomes in patients with MC.MethodsThe medical charts of 33 patients (19 women, 14 men) with 76 MC attacks from 2002 to 2014 were retrospectively reviewed. Early extubation (≤7 days) and prolonged ventilation (>15 days) during the MC were used to assess patient outcomes.ResultsAmong the 33 patients, 24 (72.7%) had positive acetylcholine receptor antibody test results and 20 (60.6%) experienced recurrent MC attacks (≥2 episodes) during follow-up (median 83.6 months, range 1.5–177 months). Plasma exchange during an MC was significantly associated with early extubation. Male sex, older age (>50 years), atelectasis, and ventilator-associated pneumonia significantly contributed to prolonged ventilation. In 22 patients who underwent thymectomy, both the duration between MC attacks and the mean number of MC attacks were significantly reduced after surgery.ConclusionsPlasma exchange during MC attacks was found to be important for early extubation; older patients and those with atelectasis or ventilator-associated pneumonia were more vulnerable to prolonged ventilation. Thymectomy may be useful to prevent recurrence of MC.