The aim of the study was to calculate the amount of surgical injury caused by systematic lymphadenectomy of mediastinum in patients operated on due to non-small cell lung cancer,with uneventful postoperative course.Th...The aim of the study was to calculate the amount of surgical injury caused by systematic lymphadenectomy of mediastinum in patients operated on due to non-small cell lung cancer,with uneventful postoperative course.The study group consisted of 11 patients with cancer of the right lung(Group 1).The control group consisted of 12 patients with left lung cancer(Group 2).In patients with right lung cancer systematic lymphadenectomy,while in patients with left lung cancer systematic sampling was performed.Serum IL-6 and IL-1ra concentration was measured before and after surgery,and on postoperative day 1,3,and 7,as well as in sputum at the end of surgery and in pleural fluid on postoperative day 1,by ELISA test.Peripheral blood lymphocyte(PBL) count was measured with flow cytometry.Time of surgery was higher in patients with right than left lung cancer(154.1±31.29) vs(119.6±24.81) min;P=0.008) .The number of resected mediastinal lymph nodes was higher in patients with right than left lung cancer(27.6±7.6) vs(11.1 ±8.1);P=0.00006) .Postoperative decrease of PBL was significantly higher in group 1 than 2(1.25±0.37) vs(1.75 ±0.64) ×103/μL;P=0.04) .No significant differences were found in serum,pleural fluid and sputum concentration of IL-6 and IL -1ra between groups.Negative correlation between concentration of these cytokines in pleural fluid and number of resected mediastinal lymph nodes was found(Spearman test for IL-6:r=-0.723;P<0.001;for IL-1ra:r=-0.768;P<0.001).Number of "positive" N2 lymph nodes did not correlate with pleural fluid concentration of cytokines.Systematic lymphadenectomy of the mediastinum causes immunosuppression,as measured by decreased count of PBL and a negative correlation between number of resected mediastinal lymph nodes and concentration of cytokines in pleural fluid.展开更多
The IL-6-STAT3 axis is critically involved in inflammation-associated carcinogenesis(IAC).How this axis is regulated to modulate IAC remains unknown.Here,we show that the plasma membrane-associated E3 ubiquitin ligase...The IL-6-STAT3 axis is critically involved in inflammation-associated carcinogenesis(IAC).How this axis is regulated to modulate IAC remains unknown.Here,we show that the plasma membrane-associated E3 ubiquitin ligase MARCH3 negatively regulates STAT3 activation triggered by IL-6,as well as another IL-6 subfamily member,Oncostatin M(OSM).MARCH3 is associated with the IL-6 receptorα-chain(IL-6Rα)and its coreceptor gp130.Biochemical experiments indicated that MARCH3 mediates the polyubiquitination of IL-6Rαat K401 and gp130 at K849 following IL-6 stimulation,leading to their translocation to and degradation in lysosomes.MARCH3 deficiency increases IL-6-and OSM-triggered activation of STAT3 and induction of downstream effector genes in various cell types.MARCH3 deficiency enhances dextran sulfate sodium(DSS)-induced STAT3 activation,increases the expression of inflammatory cytokines,and exacerbates colitis,as well as azoxymethane(AOM)/DSS-induced colitis-associated cancer in mice.In addition,MARCH3 is downregulated in human colorectal cancer tissues and associated with poor survival across different cancer types.Our findings suggest that MARCH3 is a pivotal negative regulator of IL-6-induced STAT3 activation,inflammation,and inflammation-associated carcinogenesis.展开更多
文摘The aim of the study was to calculate the amount of surgical injury caused by systematic lymphadenectomy of mediastinum in patients operated on due to non-small cell lung cancer,with uneventful postoperative course.The study group consisted of 11 patients with cancer of the right lung(Group 1).The control group consisted of 12 patients with left lung cancer(Group 2).In patients with right lung cancer systematic lymphadenectomy,while in patients with left lung cancer systematic sampling was performed.Serum IL-6 and IL-1ra concentration was measured before and after surgery,and on postoperative day 1,3,and 7,as well as in sputum at the end of surgery and in pleural fluid on postoperative day 1,by ELISA test.Peripheral blood lymphocyte(PBL) count was measured with flow cytometry.Time of surgery was higher in patients with right than left lung cancer(154.1±31.29) vs(119.6±24.81) min;P=0.008) .The number of resected mediastinal lymph nodes was higher in patients with right than left lung cancer(27.6±7.6) vs(11.1 ±8.1);P=0.00006) .Postoperative decrease of PBL was significantly higher in group 1 than 2(1.25±0.37) vs(1.75 ±0.64) ×103/μL;P=0.04) .No significant differences were found in serum,pleural fluid and sputum concentration of IL-6 and IL -1ra between groups.Negative correlation between concentration of these cytokines in pleural fluid and number of resected mediastinal lymph nodes was found(Spearman test for IL-6:r=-0.723;P<0.001;for IL-1ra:r=-0.768;P<0.001).Number of "positive" N2 lymph nodes did not correlate with pleural fluid concentration of cytokines.Systematic lymphadenectomy of the mediastinum causes immunosuppression,as measured by decreased count of PBL and a negative correlation between number of resected mediastinal lymph nodes and concentration of cytokines in pleural fluid.
基金This work was supported by grants from the National Key R&D Program of China(2017YFA0505800)the National Natural Science Foundation of China(31630045,31830024,31900556,and 32070775)+2 种基金the CAMS Innovation Fund for Medical Sciences(2019-I2M-5-071)the National Postdoctoral Program for Innovative Talents(BX20190255)the China Postdoctoral Science Foundation(2019M662706).
文摘The IL-6-STAT3 axis is critically involved in inflammation-associated carcinogenesis(IAC).How this axis is regulated to modulate IAC remains unknown.Here,we show that the plasma membrane-associated E3 ubiquitin ligase MARCH3 negatively regulates STAT3 activation triggered by IL-6,as well as another IL-6 subfamily member,Oncostatin M(OSM).MARCH3 is associated with the IL-6 receptorα-chain(IL-6Rα)and its coreceptor gp130.Biochemical experiments indicated that MARCH3 mediates the polyubiquitination of IL-6Rαat K401 and gp130 at K849 following IL-6 stimulation,leading to their translocation to and degradation in lysosomes.MARCH3 deficiency increases IL-6-and OSM-triggered activation of STAT3 and induction of downstream effector genes in various cell types.MARCH3 deficiency enhances dextran sulfate sodium(DSS)-induced STAT3 activation,increases the expression of inflammatory cytokines,and exacerbates colitis,as well as azoxymethane(AOM)/DSS-induced colitis-associated cancer in mice.In addition,MARCH3 is downregulated in human colorectal cancer tissues and associated with poor survival across different cancer types.Our findings suggest that MARCH3 is a pivotal negative regulator of IL-6-induced STAT3 activation,inflammation,and inflammation-associated carcinogenesis.
