The prognostic role of inflammation indices, such as the neutrophil-to-lymphocyte ratio (NLR) in gastric cancer (GC) remains controversial. We conducted a meta-analysis to determine the predictable value of NLR in the clinical outcome of GC patients. We searched Embase, PubMed and the Cochrane Library database for relevant randomised controlled trials. Statistical analyses were conducted to calculate the hazard ratio (HR) and 95% confidence intervals of overall survival (OS) and progression-free survival (PFS) using either random-effect or fixed-effect models according to the heterogeneity of the included studies. An analysis was carried out based on data from nine studies to evaluate the association between NLR and OS in patients with GC. Our analysis indicated that elevated pre-treatment NLR predicted poorer OS (HR: 2.16, 95% CI: 1.86 to 2.51, P < 0.001) and PFS (HR 2.78, 95% CI: 1.95 to 3.96; P < 0.00001) in patients with GC. Over a 3-year follow-up period, high NLR was a significant predictor of poor outcomes at year 1 (HR 1.99; 95% CI: 1.39 to 2.85; P = 0.0002), year 2 (HR 2.24; 95% CI: 1.69 to 2.97; P < 0.00001) and year 3 (HR 2.80; 95% CI: 1.98 to 3.96; P < 0.00001). Elevated preoperative NLR is associated with poorer rates of survival in GC patients and may play a role in GC surveillance programmes as a means of delivering more personalised cancer care.

Carotenoid Intake and Esophageal Cancer Risk: a Meta-analysis Carotenoids (lycopene, b-carotene);esophageal cancer;cancer risk;meta-analysis; This meta-analysis was conducted to evaluate the association between intake of carotenoids and risk of esophageal cancer. A systematic search using PubMed, Cochrane Library, Web of Science, Scopus, CNKI, and CBM (updated to 6 May 2012) identified ten articles meeting the inclusion criteria with 1,958 cases of esophageal cancer and 4,529 controls. Higher intake of beta-carotene, alpha-carotene, lycopene, beta-cryptoxanthin, lutein, and zeaxanthin reduced esophageal cancer risk with pooled ORs of 0.58 (95% CI 0.44, 0.77), 0.81 (95% CI 0.70, 0.94), 0.75 (95% CI 0.64, 0.86), 0.80 (95% CI 0.66, 0.97), and 0.71 (95% CI 0.59, 0.87), respectively. In subgroup analyses, beta-carotene showed protective effects against esophageal adenocarcinoma in studies located in Europe and North America. Alpha-carotene, lycopene, and beta-cryptoxanthin showed protection against esophageal squamous cell cancer. This meta-analysis suggested that higher intake of carotenoids (beta-carotene, alpha-carotene, lycopene, beta-cryptoxanthin, lutein, and zeaxanthin) is associated with lower risk of esophageal cancer. Further research with large-sample studies need to be conducted to better clarify the potentially protective mechanisms of carotenoid associations risk of different types of esophageal cancer.

Primary pulmonary enteric adenocarcinoma (PEAC) is an extremely rare variant of invasive lung cancer. It is highly heterogeneous while shares some common morphologic and immunohistochemical features with usual pulmonary adenocarcinoma (PAC) and colorectal adenocarcinoma (CRAC), making the differential diagnosis difficult. At present there are only limited studies about distinctive features of primary PEAC and the results are often inconsistent. We retrospectively analyzed total 129 primary PEACs and 50 CRACs that were published since 1991 or diagnosed in our centre. Among them eight typical samples of primary PEACs and usual PACs were detected by targeted exome sequencing. The combination of CK7+/CDX2+ acquires high sensitivity (71.3%) and specificity (82%) in differential diagnosis of PEACs from CRAC. The primary PEACs harbor a high incidence of KRAS mutation but almost absent of EGFR mutation. Moreover, compared with usual PACs, the primary PEACs have higher nonsynonymous tumor mutation burden and more frequent MMR mutation. The combination of CK7+/CDX2+ immunostaining and the distinctive genetic signatures, including low incidence of sensitivity genes mutations and high tumor mutation burden, is an important supplementary to the clinical differential diagnosis of primary PEACs. Our findings thus have significant implications for development of individualized treatment strategy in these patients.

Triple-negative breast cancer (TNBC), which is estrogen receptor (ER)-negative, progesterone receptor‑negative and is also negative for HER2 expression, remains a great clinical challenge due to its strong resistance to chemotherapy at the late stage of treatment and relatively unfavorable prognosis. Gemcitabine has been approved by the FDA/SFDA for use as a first-line therapeutic drug against advanced or metastatic breast cancer. Therefore, the clarification of the mechanisms underlying gemcitabine-acquired resistance is of particular importance for the optimal management of TNBC. A number of studies have revealed that autophagy, which has been found to protect cancer cells from anti-cancer drug-induced death, may contribute to the development of drug resistance. However, the association between autophagy and gemcitabine treatment in TNBC cells has yet to be defined. Our study clearly demonstrates that gemcitabine is able to induce mTOR-independent autophagy in human triple‑negative MDA-MB-231 breast cancer cells. In addition, we demonstrate that autophagy protects MDA-MB-231 cells from gemcitabine-induced cell growth inhibition and apoptosis, indicating that gemcitabine can activate autophagy to impair the sensitivity of MDA-MB‑231 cells. Furthermore, as shown by our results, the inhibition of gemcitabine-induced autophagy by chloroquine shifts the expression of the p53 protein, Bcl-2 family proteins and the relative Bax/Bcl-xL ratio in favor of promoting apoptosis. These results reveal that the inhibition of apoptosis may be one of the mechanisms of autophagy-induced cytoprotection in gemcitabine-treated MDA-MB-231 cells. The apoptotic and autophagic processes constitute a mutual inhibition system and jointly seal the fate of TNBC cells that are exposed to gemcitabine. Thus, our study suggests that the combination of an autophagic inhibitor and gemcitabine as a therapeutic strategy may represent a promising approach with greater clinical efficacy for patients with TNBC. However, extended preclinical trials are required to further determine the positive effects of the inhibition of autophagy on the efficacy of gemcitabine.

Inhibition of ERα/ERK/P62 cascades induces “autophagic switch” in the estrogen receptor-positive breast cancer cells exposed to gemcitabine Inhibition of ERα/ERK/P62 cascades induces “autophagic switch” in the estrogen receptor-positive breast cancer cells exposed to gemcitabine