背景与目的日间手术的种类和数量在不断扩大,部分经过选择的肺癌患者进行日间手术,临床效果如何?基于加速康复外科(enhanced recovery after surgery, ERAS)理念和外科微创技术,探索肺癌患者日间手术的操作流程及其临床应用效果。方法选...背景与目的日间手术的种类和数量在不断扩大,部分经过选择的肺癌患者进行日间手术,临床效果如何?基于加速康复外科(enhanced recovery after surgery, ERAS)理念和外科微创技术,探索肺癌患者日间手术的操作流程及其临床应用效果。方法选取2019年6月-2019年11月四川大学华西胸外科单个医疗组连续收治行肺手术患者150例,最终纳入研究患者48例,其中住院手术(inpatient surgery group, ISG)患者28例和日间手术患者(day surgery group,DSG)20例。分析两组患者平均住院日、住院费用及并发症等。结果平均住院日在日间手术组(1 d)显著低于住院手术组(7.7±2.8)d(P=0.000);平均住院费用在日间手术组(38,297.3±3408.7)$显著低于住院手术组(47,831.1±7376.1)$(P=0.000)。术后总体并发症发生率在日间手术组(5.0%)与住院手术组(3.6%)无统计学差异(P=0.812)。术后总体不良反应发生率日间手术组(10.0%)与住院手术组(17.9%)无统计学差异(P=0.729)。结论经过选择的肺癌患者行日间手术是可行的且能够加速康复。展开更多
Backgroud and Objective Lung cancer has become the most frenquent malignant tumor in the world which its mortality and morbidity is increasing fastest among all the cancers。
Dear Editor,Biomacromolecules aggregate to form membraneless organelles(MLOs)via phase separation has been observed in a variety of physiological processes over the last decade.1 However,the molecular basis of biomacr...Dear Editor,Biomacromolecules aggregate to form membraneless organelles(MLOs)via phase separation has been observed in a variety of physiological processes over the last decade.1 However,the molecular basis of biomacromolecule phase separation in cells and assembly modes of this process remain largely unknown due to a lack of available experimental methods.The dynamics of different MLOs vary widely.展开更多
Radiotherapy remains one of the major treatments for non-small cell lung cancer(NSCLC)patients;whereas intrinsic or acquired radioresistance limits its efficacy.Nevertheless,most studies so far have only focused on ac...Radiotherapy remains one of the major treatments for non-small cell lung cancer(NSCLC)patients;whereas intrinsic or acquired radioresistance limits its efficacy.Nevertheless,most studies so far have only focused on acquired resistance.The exact mechanisms of intrinsic radioresistance in NSCLC are still unclear.A few studies have suggested that epithelial–mesenchymal transition(EMT)is associated with radioresistance in NSCLC.However,little is known about whether the abnormal expression of specific microRNAs induces both EMT and radioresistance.We previously found that miR-410 has multiple roles as an oncomiRNA in NSCLC.In this study,we revealed that miR-410 overexpression promoted EMT and radioresistance,accompanied by enhanced DNA damage repair both in vitro and in vivo.Conversely,knockdown of miR-410 showed the opposite effects.We further demonstrated that PTEN was a direct target of miR-410 by using bioinformatic tools and dual-luciferase reporter assays,and the miR-410-induced EMT and radioresistance were reversed by PI3K,Akt,and mTOR inhibitors or by restoring the expression of PTEN in NSCLC cells.In addition,we preliminarily found that the expression of miR-410 was positively correlated with EMT and negatively associated with the expression of PTEN in NSCLC specimens.In summary,these results demonstrated that miR-410 is an important regulator on enhancing both NSCLC EMT and radioresistance by targeting the PTEN/PI3K/mTOR axis.The findings suggest that miR-410-induced EMT might significantly contribute to the enhanced radioresistance.Therefore,miR-410 may serve as a potential biomarker or therapeutic target for NSCLC radiotherapy.展开更多
Recent evidences show that nervous system acts as a crucial part of cancer microenvironment.Infiltration of nerve fibers into cancer microenvironment has an important active role in cancer progression.The stimulations...Recent evidences show that nervous system acts as a crucial part of cancer microenvironment.Infiltration of nerve fibers into cancer microenvironment has an important active role in cancer progression.The stimulations of both cancer growth and metastasis by members of nervous system such as neurons and glial cells have been demonstrated.However,how the nervous system is built in cancer is largely unknown.Here we show that a fraction of cancer stem cells(CSCs)derived from patients with gastric carcinoma and colorectal carcinoma are capable of producing neurons that are involved in tumor neurogenesis and tumor growth.Cancer stem cell monoclone derived from a single cancer stem cell was able to generate neurons including sympathetic and parasympathetic neurons to take part in the nervous system in cancer tissues.Knocking down the neural cell generating capability of the human CSCs inhibited the growth of xenograft tumors in mouse model.Our data demonstrate that human CSCs are able to produce one of most important components in the cancer microenvironment that are required for cancer development and progression.展开更多
Despite epidermal growth factor receptor(EGFR)tyrosine kinase inhibitors(TKl)have shown remarkable efficacy in patients with EGFR-mutant non-small cell lung cancer(NSCLC),acquired resistance inevitably develops,limiti...Despite epidermal growth factor receptor(EGFR)tyrosine kinase inhibitors(TKl)have shown remarkable efficacy in patients with EGFR-mutant non-small cell lung cancer(NSCLC),acquired resistance inevitably develops,limiting clinical efficacy.We found that TET2 was poly-ubiquitinated by E3 ligase CUL7^(FBXW11) and degraded in EGFR-TKI resistant NSCLC ells.Genetic perturbationof TET2 rendered parental cells more tolerant to TKI treatment.TET2 was stabilized by MEK1 phosphorylation at Ser 1107,while MEK1 inactivation promoted its proteasome degradation by enhancing the recruitment of CUL7^(FBXW11),Loss of TET2 resulted in the upregulation of TNF/NF-kB signaling that confers the EGFR-TKI resistance.Genetic or pharmacological inhibition of NF-kB attenuate the TKI resistance both in vitro and in vivo.Our findings exemplified how a cell growth controlling kinase MEK1 leveraged the epigenetic homeostasis by regulating TET2,and demonstrated an alternative path of non-mutational acquired EGFR-TKI resistance modulated by TET2 deficiency.Therefore,combined strategy exploiting EGFR-TKI and inhibitors of TET2/NF-κB axis holds therapeutic potential for treating NSCLC patients who suffered from this resistance.展开更多
文摘背景与目的日间手术的种类和数量在不断扩大,部分经过选择的肺癌患者进行日间手术,临床效果如何?基于加速康复外科(enhanced recovery after surgery, ERAS)理念和外科微创技术,探索肺癌患者日间手术的操作流程及其临床应用效果。方法选取2019年6月-2019年11月四川大学华西胸外科单个医疗组连续收治行肺手术患者150例,最终纳入研究患者48例,其中住院手术(inpatient surgery group, ISG)患者28例和日间手术患者(day surgery group,DSG)20例。分析两组患者平均住院日、住院费用及并发症等。结果平均住院日在日间手术组(1 d)显著低于住院手术组(7.7±2.8)d(P=0.000);平均住院费用在日间手术组(38,297.3±3408.7)$显著低于住院手术组(47,831.1±7376.1)$(P=0.000)。术后总体并发症发生率在日间手术组(5.0%)与住院手术组(3.6%)无统计学差异(P=0.812)。术后总体不良反应发生率日间手术组(10.0%)与住院手术组(17.9%)无统计学差异(P=0.729)。结论经过选择的肺癌患者行日间手术是可行的且能够加速康复。
基金supported by the grant from the Key Project of National Natural Science Foundation of China (to Qinghua ZHOU)(No.30430300)grants from the National Natural Science Foundation of China.(to Qinghua ZHOU and Lunxu LIU )(No.30070333 and No 30100075)
文摘Backgroud and Objective Lung cancer has become the most frenquent malignant tumor in the world which its mortality and morbidity is increasing fastest among all the cancers。
基金This work was jointly supported by grants from the National Natural Science Foundation of China(32090041,D.L.)the Major Research Plan of the National Natural Science Foundation of China(2016YFA0101200,D.L.).This work was also supported in part by the CAS Key Laboratory of Innate Immunity and Chronic Disease.We are grateful to Prof.Yucai Wang and Prof.Chunlei Cang for providing experimental instruments and equipments,especially confocal microscopes.We appreciate Prof.Wei Xiong and Dr.Yushu Ge for their help and advice in the process of writing this letter.We thank Mr.Zhao Yue for his help in the data processing process.We also thank our colleagues Ms.Yun Wang,Ms.Mengtong Qin and Ms.Yu Chen for their help during the experiment.
文摘Dear Editor,Biomacromolecules aggregate to form membraneless organelles(MLOs)via phase separation has been observed in a variety of physiological processes over the last decade.1 However,the molecular basis of biomacromolecule phase separation in cells and assembly modes of this process remain largely unknown due to a lack of available experimental methods.The dynamics of different MLOs vary widely.
基金supported by The National 863 Plan Project(2012AA020802)the National Science and Technology Major Projects of New Drugs(2012ZX09103301-009).
文摘Radiotherapy remains one of the major treatments for non-small cell lung cancer(NSCLC)patients;whereas intrinsic or acquired radioresistance limits its efficacy.Nevertheless,most studies so far have only focused on acquired resistance.The exact mechanisms of intrinsic radioresistance in NSCLC are still unclear.A few studies have suggested that epithelial–mesenchymal transition(EMT)is associated with radioresistance in NSCLC.However,little is known about whether the abnormal expression of specific microRNAs induces both EMT and radioresistance.We previously found that miR-410 has multiple roles as an oncomiRNA in NSCLC.In this study,we revealed that miR-410 overexpression promoted EMT and radioresistance,accompanied by enhanced DNA damage repair both in vitro and in vivo.Conversely,knockdown of miR-410 showed the opposite effects.We further demonstrated that PTEN was a direct target of miR-410 by using bioinformatic tools and dual-luciferase reporter assays,and the miR-410-induced EMT and radioresistance were reversed by PI3K,Akt,and mTOR inhibitors or by restoring the expression of PTEN in NSCLC cells.In addition,we preliminarily found that the expression of miR-410 was positively correlated with EMT and negatively associated with the expression of PTEN in NSCLC specimens.In summary,these results demonstrated that miR-410 is an important regulator on enhancing both NSCLC EMT and radioresistance by targeting the PTEN/PI3K/mTOR axis.The findings suggest that miR-410-induced EMT might significantly contribute to the enhanced radioresistance.Therefore,miR-410 may serve as a potential biomarker or therapeutic target for NSCLC radiotherapy.
基金This work was supported by the National Basic Research Program of China(to XM 2015CB942800)the Nature Science Foundation of China(to XM 81361120381to CF 81402446).
文摘Recent evidences show that nervous system acts as a crucial part of cancer microenvironment.Infiltration of nerve fibers into cancer microenvironment has an important active role in cancer progression.The stimulations of both cancer growth and metastasis by members of nervous system such as neurons and glial cells have been demonstrated.However,how the nervous system is built in cancer is largely unknown.Here we show that a fraction of cancer stem cells(CSCs)derived from patients with gastric carcinoma and colorectal carcinoma are capable of producing neurons that are involved in tumor neurogenesis and tumor growth.Cancer stem cell monoclone derived from a single cancer stem cell was able to generate neurons including sympathetic and parasympathetic neurons to take part in the nervous system in cancer tissues.Knocking down the neural cell generating capability of the human CSCs inhibited the growth of xenograft tumors in mouse model.Our data demonstrate that human CSCs are able to produce one of most important components in the cancer microenvironment that are required for cancer development and progression.
基金supported by the National Natural Science Foundation of China (Grants 31771549 to Y.C.,82103251 to J.Z.,82203153 to K.Z.,and 82203574 to S.W.)the 1.3.5 Project for Disciplines of Excellence (Grants ZYGD18021,ZYJC18009,ZYJC21002,and ZYJC21015)+1 种基金the China Postdoctoral Science Foundation (Grants 2020TQ0210 and 2021M692268 to J.Z.)Natural Science Foundation of Sichuan Province (Grant 2022NSFSC1438 to J.Z.).
文摘Despite epidermal growth factor receptor(EGFR)tyrosine kinase inhibitors(TKl)have shown remarkable efficacy in patients with EGFR-mutant non-small cell lung cancer(NSCLC),acquired resistance inevitably develops,limiting clinical efficacy.We found that TET2 was poly-ubiquitinated by E3 ligase CUL7^(FBXW11) and degraded in EGFR-TKI resistant NSCLC ells.Genetic perturbationof TET2 rendered parental cells more tolerant to TKI treatment.TET2 was stabilized by MEK1 phosphorylation at Ser 1107,while MEK1 inactivation promoted its proteasome degradation by enhancing the recruitment of CUL7^(FBXW11),Loss of TET2 resulted in the upregulation of TNF/NF-kB signaling that confers the EGFR-TKI resistance.Genetic or pharmacological inhibition of NF-kB attenuate the TKI resistance both in vitro and in vivo.Our findings exemplified how a cell growth controlling kinase MEK1 leveraged the epigenetic homeostasis by regulating TET2,and demonstrated an alternative path of non-mutational acquired EGFR-TKI resistance modulated by TET2 deficiency.Therefore,combined strategy exploiting EGFR-TKI and inhibitors of TET2/NF-κB axis holds therapeutic potential for treating NSCLC patients who suffered from this resistance.
