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Breast cancer stem cells (BCSCs) are essential for cancer growth, metastasis and recurrence. The regulatory mechanisms of BCSC interactions with the vascular niche within the tumor microenvironment (TME) and their self-renewal are currently under extensive investigation. We have demonstrated the existence of an arteriolar niche in the TME of human BC tissues. Intriguingly, BCSCs tend to be enriched within the arteriolar niche in human estrogen receptor positive (ER+) BC and bi-directionally interact with arteriolar endothelial cells (ECs). Mechanistically, this interaction is driven by the lysophosphatidic acid (LPA)/protein kinase D (PKD-1) signaling pathway, which promotes both arteriolar differentiation of ECs and self-renewal of CSCs likely via differential regulation of CD36 transcription. This study indicates that CSCs may enjoy blood perfusion to maintain their stemness features. Targeting the LPA/PKD-1 -CD36 signaling pathway may have therapeutic potential to curb tumor progression by disrupting the arteriolar niche and effectively eliminating CSCs., Jiang, Guo, Hao et al. investigate the role of the tumour microenvironment in breast cancer stem cell regulation and identify an arteriolar niche in which BCSCs tended to be enriched in human estrogen receptor positive breast cancer. Here, BCSCs are found to interact with arteriolar endothelial cells through LPA/PKD-1 signalling-mediated arteriolar differentiation of ECs and self-renewal of BCSCs.

ObjectivesBefore 2003, most children with acute lymphoblastic leukaemia (ALL) abandoned treatment, with only approximately 30% treated in China. With the development of national insurance for underprivileged patients, we assessed the current frequency and causes of treatment abandonment among patients with ALL who were enrolled in the Chinese Children’s Cancer Group ALL protocol between 2015 and 2016.MethodsDemographic, clinical and laboratory data on patients who abandoned treatment, as well as economic and sociocultural data of their families were collected and analysed. General health-related statistics were retrieved from publicly accessible databanks maintained by the Chinese government.ResultsAt a median follow-up of 119 weeks, 83 (3.1%, 95% CI 2.5% to 3.8%) of the 2641 patients abandoned treatment. Factors independently associated with abandonment included standard/high-risk ALL (OR 2.62, 95% CI 1.43 to 4.77), presence of minimal residual disease at the end of remission induction (OR 3.57, 95% CI 1.90 to 6.74) and low-income economic region (OR 3.7, 95% CI 1.89 to 7.05). According to the family members, economic constraints (50.6%, p=0.0001) were the main reason for treatment abandonment, followed by the belief of incurability, severe side effects and concern over late complications.ConclusionsThe rate of ALL treatment abandonment has been greatly reduced in China. Standard/high-risk ALL, residence in a low-income region and economic difficulties were associated with treatment abandonment.Clinical trial registration numberChiCTR-IPR-14005706, pre-results.

Yinan Jiang,1 Meiling Zhang,2 Tangxi Guo,1 Chaogang Yang,1 Chunxiao Zhang,1 Jinjin Hao2 1Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; 2Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China Background: MicroRNAs could target multiple genes by regulating the translation or degradation of mRNAs, and are involved in functions such as signal transduction pathways affecting the physiological functions of normal or tumor cells. Methods: In this study, the expressions of miRNA-21-5p in gastric cancer tissues and SGC-7901 cells were analyzed, and the effects of miRNA-21-5p on cell proliferation, migration, invasion, and apoptosis and the expressions of target proteins SMADs in SGC-7901 cells were evaluated. Inflammatory factors interleukin 1β and tumor necrosis factor α in siRNA-transfected SGC-7901 cells were determined by enzyme-linked immunosorbent assay. Results: MiRNA-21-5p was consistently upregulated in gastric cancer tissues and SGC-7901 cells compared to normal tissues or cells. The knockdown of miRNA-21-5p with antisense oligonucleotides suppressed cell proliferation, migration, and invasion as well as inflammatory response, and promoted cell apoptosis and SMAD7 expression. Conclusion: These results indicate SMAD7 may mediate the oncogenic properties of miRNA-21-5p in gastric cancer, and miRNA-21-5p would be a promising strategy for the treatment of gastric cancer. Keywords: miRNA-21-5p, gastric cancer, SMAD7, SGC-7901, migration, invasion

This network meta-analysis (NMA) was conducted to integrate different chemotherapeutic regimens for non-Hodgkin lymphoma (NHL) patients. Overall survival (OS) and complete remission (CR) were considered as main outcome indicators to evaluate the efficacy of NHL chemotherapies. OS and CR data were extracted from included studies and represented by hazard ratio and odds ratio separately. Network structure and forest plots were further included to visually present the relative efficacy among different regimens. A total of 14 qualified publications with 4,167 patients were included. In OS results, no significant difference was observed from the 1-year OS. For 2-year, 3-year and 5-year OS, patients treated by CNOP exhibited the least favorable results. Moreover, significant advantages of R-CHOP treatment over CHOP and VMP were recognized in view of 3-year OS. In respect of CR, R-HDS presented significantly better outcomes than CNOP and VMP, and no significant difference was identified when compared to CHOP in forest plot. ProMACE-CytaBOM and R-HDS possessed the compelling cumulative ranking probability in OS or CR, indicating their competitive performance in NHL treatment while R-CHOP and I-CHOP yielded desirable in terms of long-term survival and short-term survival, respectively. To conclude, ProMACE-CytaBOM, I-CHOP, R-HDS and R-CHOP were recommended to go through further evaluation to confirm their superiority in NHL treatment. CNOP and VMP were discouraged after comprehensively analyzing OS and CR from NMA results.