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Interleukin-6 signaling regulates hematopoietic stem cell emergence
Ruxiu Tie,Honghu Li,Shuyang Cai,Zuyu Liang,Wei Shan,Binsheng Wang,Yamin Tan,Weiyan Zheng,He Huang 생화학분자생물학회 2019 Experimental and molecular medicine Vol.51 No.-
Hematopoietic stem cells (HSCs) produce all lineages of mature blood cells for the lifetime of an organism. Invertebrates, HSCs derive from the transition of the hemogenic endothelium (HE) in the floor of the embryonic dorsalaorta. Most recently, a series of proinflammatory factors, such as tumor necrosis factor-α, interferon-γ, and Toll-likereceptor 4, have been confirmed to play a key role in HSC specification. However, the full complement of necessarysignaling inputs remains unknown to date. Here, we show that interleukin-6R (IL6R) via IL6 is required and sufficient forHSC generation. We found that Notch activates IL6R by regulating its expression in the HE and in HSCs. The secretionof IL6 mainly originates from HSC-independent myeloid cells, but not from HSCs and their adjacent vascularendothelial cells. In addition, blocking IL6 signaling does not affect vascular development or the production ofprimitive erythrocytes. Taken together, our results uncover a previously obscure relationship between IL6 signaling andHSC production and provide new insights into HSC regeneration using proinflammatory factors in vitro.
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Ting Liu,Qing Li,Zhen Lin,Chunhua Liu,Wei Pu,Shasha Zeng,Jun Lai,Xuebin Cai,Lisha Zhang,Shuyang Wang,Miao Chen,Wei Cao,Hongfeng Gou,Qing Zhu 대한암학회 2024 Cancer Research and Treatment Vol.56 No.2
Purpose Patients with advanced biliary tract cancer (BTC) have a poor survival. We aim to evaluate the efficacy and safety of nab-paclitaxel plus gemcitabine and cisplatin regimen in Chinese advanced BTC patients.Materials and Methods Eligible patients with locally advanced or metastatic BTC administrated intravenous 100 mg/m<sup>2</sup> nab-paclitaxel, 800 mg/m<sup>2</sup> gemcitabine, and 25 mg/m<sup>2</sup> cisplatin every 3 weeks. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS) and adverse events, while exploratory endpoint was the association of biomarkers with efficacy.Results After the median follow-up of 25.0 months, the median PFS and OS of 34 enrolled patients were 7.1 months (95% confidence interval [CI], 5.4 to 13.7) and 16.4 months (95% CI, 10.9 to 23.6), respectively. The most common treatment-related adverse events at ≥ 3 grade were neutropenia (26.5%) and leukopenia (26.5%). Survival analyses demonstrated that carcinoembryonic antigen (CEA) levels could monitor patients’ survival outcomes. A significant increase in the number of infiltrating CD4+ cells (p=0.008) and a decrease in programmed death-1–positive (PD-1+) cells (p=0.032) were observed in the response patients.Conclusion In advanced BTC patients, nab-paclitaxel plus gemcitabine and cisplatin regimen showed therapeutic potential. Potential prognostic factors of CEA levels, number of CD4+ cells and PD-1+ cells may help us maximize the efficacy benefit.
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