Background: Recent research has uncovered tumor-suppressive and oncogenic potential of miRNAs. Results: miR-214 suppresses the proliferation, migration, and invasiveness of cervical cancer cells by targeting GALNT7. Conclusion: Down-regulation of miR-214 results in overexpressed GALNT7, contributing to tumorigenesis of cervical cancer. Significance: The identification of tumor suppressor miR-214 and its oncogenic target GALNT7 in cervical cancer cells is potentially valuable for cancer diagnosis and therapy.

BackgroundOne of the putative mechanisms of tumor immune escape is based on the hypothesis that carcinomas actively create an immunosuppressed state via the expression of indoleamine 2,3-dioxygenase (IDO), both in the cancer cells and in the immune cells among the tumor-draining lymph nodes (TDLN). In an attempt to verify this hypothesis, the patterns of expression of IDO in the cancer cells and the immune cells among colon cancers were examined.MethodsSeventy-one cases of pathologically-confirmed colon cancer tissues matched with adjacent non-cancerous tissues, lymph node metastases, and TDLN without metastases were collected at the Sun Yat-sen Cancer Center between January 2000 and December 2000. The expression of IDO and Bin1, an IDO regulator, was determined with an immunohistochemical assay. The association between IDO or Bin1 expression and TNM stages and the 5-year survival rate in colon cancer patients was analyzed.ResultsIDO and Bin1 were detected in the cytoplasm of cancer cells and normal epithelium. In primary colon cancer, the strong expression of IDO existed in 9/71 cases (12.7%), while the strong expression of Bin1 existed in 33/71 cases (46.5%). However, similar staining of IDO and Bin1 existed in the adjacent non-cancerous tissues. Among the 41 cases with primary colon tumor and lymph node metastases, decreased expression of IDO was documented in the lymph node metastases. Furthermore, among the TDLN without metastases, a higher density of IDO+cells was documented in 21/60 cases (35%). Both univariate and multivariate analyses revealed that the density of IDO+cells in TDLN was an independent prognostic factor. The patients with a higher density of IDO+cells in TDLN had a lower 5-year survival rate (37.5%) than the cells with a lower density (73.1%).ConclusionThis study demonstrated paradoxical patterns of expression of IDO in colon cancer. The high density IDO+cells existed in TDLN and IDO was down-regulated in lymph nodes with metastases, implying that IDO in tumor and immune cells functions differently.

Melanomas in Chinese patients show relatively higher rates of acral and mucosal types than in other populations. However, the efficacy of checkpoint inhibitor therapies against these melanoma subtypes is not well defined. We analyzed 52 patients treated with ipilimumab, pembrolizumab, or a combination of both to evaluate the efficacy and safety of checkpoint inhibitors in Chinese patients with advanced melanoma, particularly those with acral and mucosal types. The objective response rates (ORRs) were 0, 25, and 20% for ipilimumab, pembrolizumab, and pembrolizumab plus ipilimumab, respectively. Pembrolizumab contained therapy was as effective in acral and mucosal melanoma patients (ORR 26.7 and 20%, respectively) as in non-acral cutaneous melanoma patients (ORR 26.7%). Baseline lactate dehydrogenase levels and relative lymphocyte counts were independent prognostic factors for PFS and OS. The incidences of grade 3-4 adverse events were 14% in the two monotherapy groups and 30% in the combined therapy group. The most frequent adverse events were elevation of aminotransferase, skin toxicity, thyroid dysfunction, pyrexia, and fatigue. Treatment-related rash or vitiligo was associated with a better prognosis. In summary, pembrolizumab-based therapy resulted in meaningful efficacy and good tolerability in Chinese patients with melanoma, including those with acral and mucosal types.

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ObjectiveResearch efforts have investigated therapies targeting tyrosine kinase signaling pathways. We performed a pooled analysis to determine the frequency of severe adverse effects in patients with soft tissue sarcoma treated with pazopanib, sorafenib and sunitinib.Materials and methodsWe performed a comprehensive search of PubMed, Web of Science, Ovid, the Cochrane Library and Embase databases from the drugs’ inception to May 2017 to identify clinical trials. All-grade and severe adverse events (AEs; grade≥3) were analyzed.ResultsA total of 10 trials published between 2009 and 2016, including 843 patients, were eligible for analysis. We included 424 patients (three studies) who received pazopanib 800 mg daily, 353 patients (five studies) who received sorafenib 400 mg twice daily and 66 patients (two studies) who received sunitinib 37.5 mg daily. The incidence of AEs is different among the three VEGFR-tyrosine kinase inhibitors (TKIs). Pazopanib showed higher incidence of all-grade nausea, diarrhea and hypertension compared with sorafenib and sunitinib. However, patients in the sorafenib group experienced a significantly higher frequency of all-grade rash (26.1%), hand–foot syndrome (33.4%) and mucositis (38.5%). The difference was highly significant for sorafenib vs. pazopanib in the incidence of all-grade rash (odds ratio [OR] 1.649, 95% CI 1.086–2.505, P=0.023), hand–foot syndrome (OR 3.096, 95% CI 1.271–7.544, P=0.009) and mucositis (OR 4.562, 95% CI 2.132–9.609, P<0.001). Moreover, the frequency of grade ≥3 mucositis was significantly higher in the sunitinib group compared with the pazopanib or sorafenib group (7.6% vs. 1.3%, OR 6.448, 95% CI 1.499–27.731, P=0.013).ConclusionStatistically significant differences in certain common adverse effects, such as all-grade and severe AEs, were detected among pazopanib, sorafenib and sunitinib in the current study. Early and prompt management is critically needed to avoid unnecessary dose reductions and treatment-related discontinuations.

Abstract.The relationship between TACC3, a member of the transforming acidic coiled-coil proteins (TACCs) family, and lung carcinoma remains unclear. The present study was designed to explore the prognostic and clinical significance of TACC3 in non-small cell lung cancer (NSCLC). An immunohistochemistry (IHC) assay was performed to analyze the expression of TACC3 in 195 lung cancer cases. The mRNA and protein levels of TACC3 were examined by quantitative reverse transcription-PCR or western blotting. The correlation between TACC3 expression and clinicopathological factors was analyzed by χ 2 analysis and Fisher's exact test. Kaplan-Meier analysis and the Cox proportional hazards model were used to examine the correlation of prognostic outcomes with TACC3. The results showed that the levels of TACC3 mRNA and total protein were higher in lung cancer lesions than paired non-cancerous tissues. IHC analysis revealed that TACC3 was highly expressed in 94 (48.2%) cases. The expression of TACC3 was strongly correlated with smoking status, histological classification, differentiation, cytokeratin 19 fragment levels, T stage and the clinical stage of NSCLC patients. Univariate and multivariate analyses demonstrated that TACC3 is a useful biomarker for NSCLC prognosis. The low TACC3 expression group exhibited better progression-free survival (PFS) among patients who received anti-microtubule chemotherapy. In conclusion, the results showed that a high level of TACC3 expression was correlated with advanced clinicopathological classifications, poor overall survival (OS) and poor recurrence-free survival (RFS) in NSCLC patients.Our findings indicate that TACC3 is a potential prognostic marker and therapeutic target for NSCLC.

This study aimed to determine the tolerability of Chinese melanoma patients, particularly those with hepatitis B virus (HBV) infection, to immune checkpoint inhibitor therapy. Patients with metastatic melanoma who received anti-cytotoxic T lymphocyte-associated antigen-4 antibody (ipilimumab) or anti-programmed death 1 antibody (pembrolizumab) therapy at our hospital between August 2012 and July 2015 were retrospectively reviewed. Adverse events were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0. Twenty-three patients with advanced melanoma were included; nine and 10 patients received infusions of ipilimumab and pembrolizumab, respectively, whereas four patients received concurrent ipilimumab and pembrolizumab therapy. There was no cessation of treatment because of agent-related adverse events in any patient. Immune-related adverse events were observed in 44% (4/9), 60% (6/10), 100% (4/4), and 61% (14/23) of patients receiving ipilimumab, pembrolizumab, concomitant ipilimumab and pembrolizumab, and any treatment, respectively. The most frequent immune-related adverse events were endocrine disorders (39%, 9/23), liver function abnormalities (22%, 5/23), and dermatological events (17%, 4/23). There were no gastrointestinal reactions. Toxicities were usually mild and easily managed; only 13% (3/23) of patients had grade 3 adverse events and none experienced grade 4 events or treatment-related death. No additional toxicity nor severe hepatotoxicity was observed in 11 patients who had previous HBV infection. The recommended anti-cytotoxic T lymphocyte-associated antigen-4 and anti-programmed death 1 antibody doses were well tolerated by Chinese patients. Thus, immune checkpoint inhibitors appear to be effective and safe in metastatic melanoma patients, including those with pre-existing HBV infection.

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