Tamoxifen is still the most commonly used endocrine therapy drug for estrogen receptor (ER)-positive breast cancer patients and has an excellent outcome, but tamoxifen resistance remains a great impediment to successful treatment. Recent studies have prompted an anti-tumor effect of aspirin. Here, we demonstrated that aspirin not only inhibits the growth of ER-positive breast cancer cell line MCF-7, especially when combined with tamoxifen, but also has a potential function to overcome tamoxifen resistance in MCF-7/TAM. Aspirin combined with tamoxifen can down regulate cyclinD1 and block cell cycle in G0/G1 phase. Besides, tamoxifen alone represses c-myc, progesterone receptor (PR) and cyclinD1 in MCF-7 cell line but not in MCF-7/TAM, while aspirin combined with tamoxifen can inhibit the expression of these proteins in the resistant cell line. When knocking down c-myc in MCF-7/TAM, cells become more sensitive to tamoxifen, cell cycle is blocked as well, indicating that aspirin can regulate c-myc and cyclinD1 proteins to overcome tamoxifen resistance. Our study discovered a novel role of aspirin based on its anti-tumor effect, and put forward some kinds of possible mechanisms of tamoxifen resistance in ER-positive breast cancer cells, providing a new strategy for the treatment of ER-positive breast carcinoma.

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Background Inflammatory response and nutritional status are associated with cancer development and progression. The purpose of this study was to explore whether the preoperative fibrinogen-albumin ratio index (FARI) is related to prognosis and chemoradiotherapy outcome of radical surgery after neoadjuvant chemoradiotherapy (NCRT) in patients with locally advanced rectal cancer (LARC). Methods In total, 123 patients with LARC who underwent radical surgery after NCRT between June 2012 and December 2018 were collected in this study. Time-dependent receiver operating characteristic (ROC) curve analysis was made to evaluate the ability of the markers for forecasting prognosis. The correlation between FARI and clinicopathological parameters was analyzed. The Kaplan–Meier survival analysis, univariate and multivariate analysis based on Cox proportional hazards models, and subgroup analysis were performed to evaluate overall survival (OS) and disease-free survival (DFS). A nomogram was constructed to evaluate the predictive role of FARI in DFS. Results The ROC curve analysis showed that the ability of FARI on DFS prediction was superior to those of other inflammatory markers and carcinoembryonic antigen (CEA) (P<0.05). Based on the Youden’s index, the optimal cut-off value of FARI was 8.8%. High FARI patients (>8.8%) showed a poor response to NCRT and a decreased DFS rate (P<0.05). In addition, multivariate analysis revealed that FARI (HR=3.098, P=0.033), neutrophil-to-lymphocyte ratio (NLR), and postoperative T stage were independent prognostic factors for DFS in TNM stage III LARC patients. However, FARI failed to distinguish patients with poor OS. Harrell’s concordance index (C-index) of the nomogram containing FARI (0.807) was obviously higher than that without it (0.732) among LARC patients who underwent radical surgery after NCRT. Moreover, multivariate analysis revealed FARI (OR=3.044, P=0.012) as an independent predictor for response to NCRT. Conclusion Among LARC patients who underwent radical surgery after NCRT, preoperative FARI is an independent prognostic factor for DFS and an independent predictor for response to NCRT.

Background: There is no consensus regarding which reconstruction methods are superior after laparoscopic distal gastrectomy (LDG). This study compared four reconstruction methods after LDG for gastric cancer. Methods: Literature in EMBASE, PubMed, and the Cochrane Library was screened to compare Billroth I (B-I), Billroth II (B-II), Roux-en-Y (RY), and uncut Roux-en-Y (URY) anastomoses after LDG for gastric cancer. A Bayesian network meta-analysis (NMA) was conducted to compare these methods. Results: Eighteen studies involving 4347 patients were eligible for our NMA. The operative time in RY anastomosis was longer than that in B-I and B-II anastomoses. Blood loss and risk of gastrointestinal motility dysfunction were greater with RY anastomosis than with URY or B-I anastomosis. Furthermore, URY anastomosis was superior to the other 3 reconstruction methods for preventing food residue. For remnant gastritis, RY anastomosis was significantly superior to B-I and B-II anastomoses, whereas URY anastomosis was significantly superior to B-II anastomosis. In addition, RY and URY anastomoses were better than B-I and B-II anastomoses for preventing bile reflux. Conclusions: URY anastomosis tended to be a more favorable reconstruction method after LDG due to its operative simplicity and reduced long-term complications.