We previously reported that tumor-infiltrating interleukin (IL)-17A-producing cells play a protective role in human esophageal squamous cell carcinoma (ESCC). However, the potential mechanisms involved remain unclear. In the present study, we investigated the effects of IL-17A on immune cell recruitment and function in ESCC. In vitro chemotaxis assays using the ESCC cell lines EC109 and KYSE30 demonstrated that although IL-17A showed no significant direct effects on the migration of T cells, natural killer (NK) cells as well as dendritic cells (DCs), it could induce ESCC tumor cells to produce inflammatory chemokines, for example, CXCL9, CXCL10 and CCL2, CCL20, which are associated with the migration of T cells, NK cells, and DCs, respectively. In addition, IL-17A enhanced the cytotoxic effects of NK cells against tumor cells by augmenting the expression of cytotoxic molecules, for example, tumor necrosis factor-α, interferon-γ, Perforin, and Granzyme B and activation receptors, for example, NKp46, NKp44, NTB-A, and NKG2D on NK cells. Furthermore, immunohistochemical analysis revealed that the density of IL-17A-producing cells was positively and significantly associated with the density of CD1a DCs in tumor tissues. With the analyses of 181 ESCC patients, we found a correlation of higher number of tumor-infiltrating CD1a DCs with significantly improved overall survival of patients with ESCC. This study provides further understanding of the roles of Th17 cells in ESCC, which may contribute to the development of novel cancer immunotherapy strategies.

(-)-Epigallocatechin-3-gallate (EGCG) is the most abundant catechin in green tea. In this study, we found that hepatitis C virus (HCV) infection was significantly suppressed by EGCG in an HCV cell culture (HCVcc) system using a JFH1-GFP chimeric virus, with a 50 % effective concentration (EC(50)) of 17.9 μM. The inhibitory activity of EGCG was confirmed by monitoring HCV RNA and protein expression levels in Huh7.5.1 cells infected with the JFH1 virus. Moreover, we demonstrated that the inhibitory mechanisms of EGCG were attributable to the suppression of both the HCV entry and RNA replication steps, although EGCG had little effect on translation directed by the viral internal ribosome entry site (IRES). Furthermore, HCV could be rapidly eliminated from cell cultures after two and five passages in the presence of 50 and 25 μM EGCG, respectively. These results indicate that EGCG is a potential candidate as a preventive and antiviral drug for HCV infection.

Postoperative immunotherapy with CIK cell transfusion may be an effective adjuvant treatment for improving the outcomes of HCC patients; >8 cycles of CIK cell transfusion may ensure that patients derive maximal benefits. Moreover, patients with large tumors might benefit more from CIK cell adjuvant treatment than patients with small tumors.

BackgroundIn this study, we established a hypothetical tumor-lodds-metastasis (TLM) and tumor-ratio-metastasis (TRM) staging system. Moreover, we compared them with the 7th edition of American Joint Committee on Cancer tumor-nodes-metastasis (AJCC TNM) staging system in gastric cancer patients after D2 resection.MethodsA total of 1000 gastric carcinoma patients receiving treatment in our center were selected for the analysis. Finally, 730 patients who received D2 resection were retrospectively studied. Patients were staged using the TLM, TRM and the 7th edition AJCC TNM system. Survival analysis was performed with a Cox regression model. We used two parameters to compare the TNM, TRM and TLM staging system, the −2log likelihood and the hazard ratio.ResultsThe cut points of lymph node ratio (LNR) were set as 0, 0–0.3, 0.3–0.6, 0.6–1.0. And for the log odds of positive lymph nodes (LODDS), the cut points were established as≤−0.5, −0.5-0, 0-0.5, >0.5. There were significant differences in survival among patients in different LODDS classifications for each pN or LNR groups. When stratified by the LODDS classifications, the prognosis was highly homologous between those in the according pN or LNR classifications. Multivariate analysis showed that TLM staging system was better than the TRM or TNM system for the prognostic evaluation.ConclusionsThe TLM system was superior to the TRM or TNM system for prognostic assessment of gastric adenocarcinoma patients after D2 resection.

Na+-dependent glucose cotransporter (SGLT1), reported overexpression in tumor tissues while its clinical significance was not established, and epidermal growth factor receptor (EGFR) with potential relation to SGLT1 were studied in order to investigate their clinical significance in colorectal cancer (CRC). Eighty-five patients of CRC who received chemotherapy in Sun Yat-sen Cancer Center from March 1st 2005 to December 31st 2008 were enrolled. SGLT1 and EGFR expression in these cancer tissues and 28 normal tissues were tested by immunohistochemistry. (1) Expression of SGLT1 (P = 0.00) and EGFR (P = 0.01) in cancer tissues was higher than that in normal tissues. (2) Their expression related with clinical stage (P = 0.03 and P = 0.02), but not with other clinical characteristics. (3) For first-line chemotherapy, expression of SGLT1 (P = 0.06 and P = 0.21) and EGFR (P = 0.37 and P = 0.31) had no influence on objective response rate (ORR) and disease control rate (DCR). EGFR overexpression was associated with lower disease-free survival (P = 0.00) and overall survival (P = 0.01), while SGLT1 did not (P = 0.79 and P = 0.34). Conclusions Both SGLT1 and EGFR overexpression in CRC was related to higher clinical stages. SGLT1 had a potential impact on the ORR of first-line chemotherapy in CRC. EGFR was associated with prognosis, while SGLT1 did not.

BackgroundIt has been suggested that autophagy-related Beclin 1 plays a critical role in the regulation of tumor development and/or progression, but its prognostic significance and relationship with Bcl-xL expression in ovarian carcinoma are unclear.Methodology/Principal FindingsIn the present study, the methods of Western blotting and immunohistochemistry (IHC) were utilized to investigate the expression status of Beclin 1 and Bcl-xL in fresh ovarian tissues and paraffin-embedded epithelial ovarian tumor tissues. Decreased expression of Beclin 1 was examined by IHC in 8.3% of normal ovaries, in 15.4% of cystadenomas, in 20.0% of borderline tumors, and in 55.6% of ovarian carcinomas, respectively. In ovarian carcinomas, decreased expression of Beclin 1 was correlated closely with ascending histological grade, later pT/pN/pM status and/or advanced clinical stage (P<0.05). In univariate survival analysis, a highly significant association between low-expressed Beclin 1 and shortened patient survival was evaluated in ovarian carcinoma patients (P<0.01), and Beclin 1 expression was an independent prognostic factor as evidenced by multivariate analysis (P = 0.013). In addition, decreased expression of Beclin 1 was inversely correlated with altered expression of Bcl-xL in ovarian carcinoma cohort, and combined analysis further showed that the low Beclin 1/high Bcl-xL group had the lowest survival rate.Conclusions/SignificanceOur findings suggest that Beclin 1 expression, as examined by IHC, could be served as an additional tool in identifying ovarian carcinoma patients at risk of tumor progression, and predicting patient survival in ovarian carcinomas with increased expression of Bcl-xL.

Purpose: Triple-negative breast cancer (TNBC) is a high risk form of this disease, even after surgery, due to the absence of targets for hormone treatment and anti-Her-2 therapy. Chemotherapy is the main therapeutic strategy for such patients with breast cancer, although the outcome is often unsatisfactory. Thus, the development of combination adjuvant therapies is essential for improved prognosis in patients with TNBC. In this study, we investigated the efficacy of a sequential combination of cytokine-induced killer cell (CIK) infusion and chemotherapy for patients with post-mastectomy TNBC.Experimental Design: From 2008 to 2012, 90 patients with post-mastectomy TNBC were included in this retrospective study: 45 cases received chemotherapy alone or with sequential radiotherapy; a further 45 cases received chemotherapy with/without radiotherapy and sequential CIK infusion.Results: Survival analysis showed significantly higher disease-free survival (DFS) and overall survival (OS) rates in the CIK treatment group compared with the control group (P ¼ 0.0382, P ¼ 0.0046, respectively; log-rank test). Multivariate survival analysis showed that CIK adjuvant treatment was an independent prognostic factor for OS of patients with TNBC. In subgroup analyses, CIK adjuvant treatment significantly increased the DFS rate of patients with pathologic grade 3, and significantly increased the OS rate of patients in N1, N2, N3, IIB, III TNM (tumor-node-metastasis) stages, and with pathologic grade 3.Conclusions: These data indicate that adjuvant CIK treatment combined with chemotherapy is an effective therapeutic strategy to prevent disease recurrence and prolong survival of patients with TNBC, particularly those with lymph node metastasis, advanced TNM stage, and poor pathologic grade. Clin Cancer Res; 20(11); 3003-11. Ó2014 AACR.

Elevated activity of the eukaryotic translation initiation factor 4E (eIF4E) plays crucial roles in tumorigenesis and disease progression by disproportionately increasing translation of mRNAs coding proteins that play significant roles in all aspects of malignancy, providing that eIF4E as an attractive target for therapeutic intervention. In this study, we showed that inhibition of eIF4E by small interfering RNAs (siRNA) resulted in cell cycle arrest and suppression of colony formation in MDA-MB-231 triple-negative (TN) breast cancer cells. Migration transwell assay revealed that repression of eIF4E effectively inhibited motility of MDA-MB-231 cancer cells. Importantly, we showed that silencing of eIF4E sensitized MDA-MB-231 cells to chemotherapeutic drugs of cisplatin, adriamycin, paclitaxel and docetaxel as assessed by MTT assay. Moreover, Western blot assay showed that eIF4E siRNA increased Bax/Bcl-2 ratio in MDA-MB-231 cells. Taken together, we showed that knockdown of eIF4E suppressed cell growth and migration, enhanced chemosensitivity, suggesting a potential therapeutic target in TN breast carcinoma.