2018年3月8?9日,中国临床肿瘤学会(Chinese Society of Clinical Oncology,CSCO)和中国抗癌协会肺癌专业委员会联合主办了第15届“中国肺癌高峰论坛”。本次论坛的主题为“聚焦中枢神经系统转移:精确诊断,精准治疗”。晚期肺癌患者往往...2018年3月8?9日,中国临床肿瘤学会(Chinese Society of Clinical Oncology,CSCO)和中国抗癌协会肺癌专业委员会联合主办了第15届“中国肺癌高峰论坛”。本次论坛的主题为“聚焦中枢神经系统转移:精确诊断,精准治疗”。晚期肺癌患者往往合并脑转移,在1 000多例的肺癌尸检结果中,肺癌脑转移发生率23%~36%,是脑转移性肿瘤中最常见的类型,且通常预后较差[1]。目前肺癌脑(膜)转移的综合治疗管理和治疗结果,仍不令人满意,治疗效果不佳,中位总生存时间16个月,其中脑膜转移的患者则仅为4.5个月左右[2?5]。近10年肺癌的治疗出现了革命性的改变,但肺癌脑转移的诊断和治疗成了提高肺癌长期生存率的瓶颈。临床医师及科研工作者,应如何对脑转移进行准确及时的诊断?在众多的分型分类体系中,又该如何参考应用?如何全面地对脑转移患者的颅内/颅外病灶进行合理评估?对于伴有驱动基因敏感突变的脑转移患者群体,应怎样对待酪氨酸激酶抑制剂(tyrosine kinase inhibitor,TKI)治疗的定位和应用时机?随着血管生成抑制剂和免疫检查点Checkpoint抑制剂的应用发展,新的治疗选择在肺癌脑转移治疗应用中又该如何管理?以上都是肺癌脑转移综合管理中的疑点和难点,急需解答和形成共识以指导临床实践。本次肺癌高峰论坛,综合近年来发表的前瞻性及回顾性重要研究结果、结合我国肺癌脑转移治疗管理的实际情况,与会专家们就肺癌脑转移的综合管理进行了详细的讨论和各抒己见的争辩,最后达成了以下四点共识。展开更多
2017年3月3-4日，中国临床肿瘤学会（Chinese Society of Clinical Oncology，CSCO）和中国抗癌协会肺癌专业委员会联合主办了第十四届“中国肺癌高峰论坛”。本次论坛的主题是“精准与联合：共谱免疫治疗新乐章”。检查点抑制剂（Check...2017年3月3-4日，中国临床肿瘤学会（Chinese Society of Clinical Oncology，CSCO）和中国抗癌协会肺癌专业委员会联合主办了第十四届“中国肺癌高峰论坛”。本次论坛的主题是“精准与联合：共谱免疫治疗新乐章”。检查点抑制剂（Checkpoint inhibitor）因其对多肿瘤类别广泛的适用性及能带来持久的有效缓解，短期内在全球范围掀起了免疫治疗的狂潮。而在非小细胞肺癌患者中，免疫治疗同样带来了令人欣喜的临床获益。展开更多
Background Decorin is a small leucine-rich proteoglycan and it plays an important role in regulation of cell growth and migration in various tumor cell lines. Decorin was found down-regulated in non-small cell lung ca...Background Decorin is a small leucine-rich proteoglycan and it plays an important role in regulation of cell growth and migration in various tumor cell lines. Decorin was found down-regulated in non-small cell lung cancer tissue and may be involved in regulation of lung cancer development. Methods In this study, lentivirus-mediated RNA interference and over expression were employed to change the expression levels of decorJn Jn lung cancer A549 cells. We tested the cell cycle of A549 cells and the expression of transforming growth factor （TGF）-[31, cyclin D1, epidermal growth factor receptor （EGFR）, P53, and P21. Results We found that up-regulation of decorin could inhibit proliferation, block cell cycle at G1 and decrease invasive activity of A549 cells. Moreover, we also show that up-regulation of decorin induced significant decreases of TGF-131, cyclin D1 expression, phosphorylation of EGFR, and increases of P53 and P21 expression. Opposite results were observed in A549 cells with down-regulation of decorin. Conclusion Our results suggest that decorin is a key regulator involved in proliferation and migration ofA549 cells.展开更多
Background Staphylococcus aureus （S. aureus） remains as an important microbial pathogen resulting in community and nosocomial acquired infections with significant morbidity and mortality. Few reports for S. aureus i...Background Staphylococcus aureus （S. aureus） remains as an important microbial pathogen resulting in community and nosocomial acquired infections with significant morbidity and mortality. Few reports for S. aureus in lower respiratory tract infections （LRTIs） have been documented. The aim of this study was to explore the molecular epidemiology of S. aureus in LRTIs in China.Methods A multicenter study of the molecular epidemiology of S. aureus in LRTIs was conducted in 21 hospitals in Beijing, Shanghai and twelve other provinces from November 2007 to February 2009. All the collected S. aureus strains were classified as minimum inhibitory concentration （MIC）, mecA gene, virulence genes Panton-Valentine Leukocidin （PVL） and y-hemolysin （hlg）, staphylococcal cassette chromosome mec （SCCmec） type, agr type, and Multilocus Sequence Typinq （MLST）.Results Totally, nine methicillin-sensitive S. aureus （MSSA） and 29 methicillin-resistant S. aureus （MRSA） strains were isolated after culture from a total of 2829 sputums or bronchoalveolar lavages. The majority of MRSA strains （22/29） had a MIC value of 〉512 μg/ml for cefoxitin. The mecA gene acting as the conservative gene was carried by all MRSA strains. PVL genes were detected in only one S. aureus strain （2.63%, 1/38）. The hlg gene was detected in almost the all S. aureus （100% in MSSA and 96.56% in MRSA strains）. About 75.86% of MRSA strains carried SCCmec Ⅲ. Agr type 1 was predominant （78.95%） among the identified three agr types （agr types 1,2, and 3）. Totally, ten sequence type （ST） of S. aureus strains were detected. A new sequence type （ST1445） was found besides confirming ST239 as the major sequence type （60.53%）. A dendrogram generated from our own MLST database showed all the bootstrap values 〈50%. Conclusion Our preliminary epidemiology data show SCCmec Ⅲ, ST239 and agr type 1 of S. aureus as the predominant strains in LRTIs in Mainland of China.展开更多
Background Acinetobacter baumanii （A. baumanii ） remains an important microbial pathogen resulting in nosocomialacquired infections with significant morbidity and mortality. The mechanism by which nosocomial bacteri...Background Acinetobacter baumanii （A. baumanii ） remains an important microbial pathogen resulting in nosocomialacquired infections with significant morbidity and mortality. The mechanism by which nosocomial bacteria, like A. baumanii, attain multidrug resistance to antibiotics is of considerable interest. The aim in this study was to investigate the spread status of antibiotic resistance genes, such as multiple 13-1actamase genes and aminoglycoside-modifying enzyme genes, from A. baumanii strains isolated from patients with lower respiratory tract infections （LRTIs）. Methods Two thousand six hundred and ninety-eight sputum or the bronchoalveolar lavage samples from inpatients with LRTIs were collected in 21 hospitals in the mainland of China from November 2007 to February 2009. All samples were routinely inoculated. The isolated bacterial strains and their susceptibility were analyzed via VITEK-2 expert system. Several kinds of antibiotic resistant genes were further differentiated via polymerase chain reaction and sequencing methods. Results Totally, 39 A. baumanii strains were isolated from 2698 sputum or bronchoalveolar lavage samples. There was not only a high resistant rate of the isolated A. baumanfi strains to ampicillin and first- and second-generation cephalosporins （94.87%, 100% and 97.44%, respectively）, but also to the third-generation cephalosporins （ceftriaxone at 92.31%, ceftazidine at 51.28%） and imipenem （43.59%） as well. The lowest antibiotic resistance rate of 20.51% was found to amikacin. The OXA-23 gene was identified in 17 strains of A. baumanii, and the AmpC gene in 23 strains. The TEM-1 gene was carried in 15 strains. PER-1 and SHV-2 genes were detected in two different strains. Aminoglycoside-modifying enzyme gene aac-3-1a was found in 23 strains, and the aac-6＂lb gene in 19 strains, aac-3-1a and aac-6＂lb genes hibernated in three A. baumanfi strains that showed no drug-resistant phenotype. Conclusions A. baumanii can carry multiple drug-resistant genes at the same time and result in multi-drug resistance. Aminoglycoside-modifying enzyme genes could be hibernating in aminoglycoside sensitive strains without expressing their phenotype.展开更多
Background Airway symptoms in asthma are related to decrease of epinephrine secretion, which may be ascribed to elevated nerve growth factor （NGF） in the organism. The aim of this study was to monitor the neuroendoc...Background Airway symptoms in asthma are related to decrease of epinephrine secretion, which may be ascribed to elevated nerve growth factor （NGF） in the organism. The aim of this study was to monitor the neuroendocrine alteration in the adrenal medulla of asthmatic rats. Methods Sixteen rats were randomly divided into two groups （n=-8）, control group and asthma group, and the asthmatic rats were sensitized and challenged with ovalbumin （OVA）. The levels of NGF, epinephrine and norepinephrine in serum were detected by enzyme linked immunosorbent assay （ELISA）, the NGF expression in adrenal medulla was detected by immunohistochemistry, and the changes in the ultrastructure of the adrenal medulla was observed by electron microscopy. Results The NGF expression was increased in asthmatic rats compared with control rats. Compared with control rats, the results indicated that the epinephrine level was decreased in asthmatic rats, but no significant difference was found in norepinephrine levels. We found more ganglion cells in the adrenal medulla of asthmatic rats than in control rats, with NGF immunostaining mainly located in these ganglion cells. Electron microscopic images showed the density of chromaffin granula decreased and there was shrunken nucleolemma in the adrenal medullary cells of asthmatic rats. Conclusion The innervation of the adrenal medulla is changed in asthmatic rats, and it may contribute to the epinephrine decrease in asthma.展开更多
Background The extracellular release of the danger signal high mobility group box-1 （HMGB1） has been implicated in the pathogenesis and outcomes of sepsis. Understanding the mechanisms responsible for HMGB1 release ...Background The extracellular release of the danger signal high mobility group box-1 （HMGB1） has been implicated in the pathogenesis and outcomes of sepsis. Understanding the mechanisms responsible for HMGB1 release can lead to the identification of targets that may inhibit this process. The transcription factor interferon regulatory factor-1 （IRF-1） is an important mediator of innate immune responses and has been shown to participate in mortality associated with endotoxemia; however, its role in mediating the release of HMGB1 in these settings is unknown. Methods Male IRF-1 knockout （KO） and age matched C57BL/6 wild type （WT） mice were given intraperitoneal （IP） injections of lipopolysaccharide （LPS）. In some experiments, 96 hours survival rates were observed. In other experiments, mice were sacrificed 12 hours after LPS administration and sera were harvested for future analysis. In in vitro study, RAW 264.7 murine monocyte/macrophage-like cells or primary peritoneal macrophage obtained from IRF-1 KO and WT mice were cultured for LPS mediated HMGB1 release analysis. And the mechanism for HMGB1 release was analyzed by immune-precipitation. Results IRF-1 KO mice experienced less mortality, and released less systemic HMGB1 compared to their WT counterparts. Exogenous administration of recombinant HMGB1 to IRF-1 KO mice returned the mortality rate to that seen originally in IRF-1 WT mice. Using cultures of peritoneal macrophages or RAW264.7 cells, in vitro LPS stimulation induced the release of HMGB1 in an IRF-1 dependent manner. And the janus associated kinase （JAK）-IRF-1 signal pathway appeared to participate in the signaling mechanisms of LPS-induced HMGB1 release by mediating acetylation of HMGBI. Conclusion IRF-1 plays a role in LPS induced release of HMGB1 and therefore may serve as a novel target in sepsis~展开更多
文摘2018年3月8?9日,中国临床肿瘤学会(Chinese Society of Clinical Oncology,CSCO)和中国抗癌协会肺癌专业委员会联合主办了第15届“中国肺癌高峰论坛”。本次论坛的主题为“聚焦中枢神经系统转移:精确诊断,精准治疗”。晚期肺癌患者往往合并脑转移,在1 000多例的肺癌尸检结果中,肺癌脑转移发生率23%~36%,是脑转移性肿瘤中最常见的类型,且通常预后较差[1]。目前肺癌脑(膜)转移的综合治疗管理和治疗结果,仍不令人满意,治疗效果不佳,中位总生存时间16个月,其中脑膜转移的患者则仅为4.5个月左右[2?5]。近10年肺癌的治疗出现了革命性的改变,但肺癌脑转移的诊断和治疗成了提高肺癌长期生存率的瓶颈。临床医师及科研工作者,应如何对脑转移进行准确及时的诊断?在众多的分型分类体系中,又该如何参考应用?如何全面地对脑转移患者的颅内/颅外病灶进行合理评估?对于伴有驱动基因敏感突变的脑转移患者群体,应怎样对待酪氨酸激酶抑制剂(tyrosine kinase inhibitor,TKI)治疗的定位和应用时机?随着血管生成抑制剂和免疫检查点Checkpoint抑制剂的应用发展,新的治疗选择在肺癌脑转移治疗应用中又该如何管理?以上都是肺癌脑转移综合管理中的疑点和难点,急需解答和形成共识以指导临床实践。本次肺癌高峰论坛,综合近年来发表的前瞻性及回顾性重要研究结果、结合我国肺癌脑转移治疗管理的实际情况,与会专家们就肺癌脑转移的综合管理进行了详细的讨论和各抒己见的争辩,最后达成了以下四点共识。
文摘2017年3月3-4日，中国临床肿瘤学会（Chinese Society of Clinical Oncology，CSCO）和中国抗癌协会肺癌专业委员会联合主办了第十四届“中国肺癌高峰论坛”。本次论坛的主题是“精准与联合：共谱免疫治疗新乐章”。检查点抑制剂（Checkpoint inhibitor）因其对多肿瘤类别广泛的适用性及能带来持久的有效缓解，短期内在全球范围掀起了免疫治疗的狂潮。而在非小细胞肺癌患者中，免疫治疗同样带来了令人欣喜的临床获益。
基金This work was supported by the grants from Research Fund for the Doctoral Program of Higher Education of China （No.20100072120060）, the Shanghai Municipal Natural Science Foundation （No. 10ZR1425000）, the Foundation of the Shanghai Pulmonary Hospital （No. 20090018）.
文摘Background Decorin is a small leucine-rich proteoglycan and it plays an important role in regulation of cell growth and migration in various tumor cell lines. Decorin was found down-regulated in non-small cell lung cancer tissue and may be involved in regulation of lung cancer development. Methods In this study, lentivirus-mediated RNA interference and over expression were employed to change the expression levels of decorJn Jn lung cancer A549 cells. We tested the cell cycle of A549 cells and the expression of transforming growth factor （TGF）-[31, cyclin D1, epidermal growth factor receptor （EGFR）, P53, and P21. Results We found that up-regulation of decorin could inhibit proliferation, block cell cycle at G1 and decrease invasive activity of A549 cells. Moreover, we also show that up-regulation of decorin induced significant decreases of TGF-131, cyclin D1 expression, phosphorylation of EGFR, and increases of P53 and P21 expression. Opposite results were observed in A549 cells with down-regulation of decorin. Conclusion Our results suggest that decorin is a key regulator involved in proliferation and migration ofA549 cells.
文摘Background Staphylococcus aureus （S. aureus） remains as an important microbial pathogen resulting in community and nosocomial acquired infections with significant morbidity and mortality. Few reports for S. aureus in lower respiratory tract infections （LRTIs） have been documented. The aim of this study was to explore the molecular epidemiology of S. aureus in LRTIs in China.Methods A multicenter study of the molecular epidemiology of S. aureus in LRTIs was conducted in 21 hospitals in Beijing, Shanghai and twelve other provinces from November 2007 to February 2009. All the collected S. aureus strains were classified as minimum inhibitory concentration （MIC）, mecA gene, virulence genes Panton-Valentine Leukocidin （PVL） and y-hemolysin （hlg）, staphylococcal cassette chromosome mec （SCCmec） type, agr type, and Multilocus Sequence Typinq （MLST）.Results Totally, nine methicillin-sensitive S. aureus （MSSA） and 29 methicillin-resistant S. aureus （MRSA） strains were isolated after culture from a total of 2829 sputums or bronchoalveolar lavages. The majority of MRSA strains （22/29） had a MIC value of 〉512 μg/ml for cefoxitin. The mecA gene acting as the conservative gene was carried by all MRSA strains. PVL genes were detected in only one S. aureus strain （2.63%, 1/38）. The hlg gene was detected in almost the all S. aureus （100% in MSSA and 96.56% in MRSA strains）. About 75.86% of MRSA strains carried SCCmec Ⅲ. Agr type 1 was predominant （78.95%） among the identified three agr types （agr types 1,2, and 3）. Totally, ten sequence type （ST） of S. aureus strains were detected. A new sequence type （ST1445） was found besides confirming ST239 as the major sequence type （60.53%）. A dendrogram generated from our own MLST database showed all the bootstrap values 〈50%. Conclusion Our preliminary epidemiology data show SCCmec Ⅲ, ST239 and agr type 1 of S. aureus as the predominant strains in LRTIs in Mainland of China.
文摘Background Acinetobacter baumanii （A. baumanii ） remains an important microbial pathogen resulting in nosocomialacquired infections with significant morbidity and mortality. The mechanism by which nosocomial bacteria, like A. baumanii, attain multidrug resistance to antibiotics is of considerable interest. The aim in this study was to investigate the spread status of antibiotic resistance genes, such as multiple 13-1actamase genes and aminoglycoside-modifying enzyme genes, from A. baumanii strains isolated from patients with lower respiratory tract infections （LRTIs）. Methods Two thousand six hundred and ninety-eight sputum or the bronchoalveolar lavage samples from inpatients with LRTIs were collected in 21 hospitals in the mainland of China from November 2007 to February 2009. All samples were routinely inoculated. The isolated bacterial strains and their susceptibility were analyzed via VITEK-2 expert system. Several kinds of antibiotic resistant genes were further differentiated via polymerase chain reaction and sequencing methods. Results Totally, 39 A. baumanii strains were isolated from 2698 sputum or bronchoalveolar lavage samples. There was not only a high resistant rate of the isolated A. baumanfi strains to ampicillin and first- and second-generation cephalosporins （94.87%, 100% and 97.44%, respectively）, but also to the third-generation cephalosporins （ceftriaxone at 92.31%, ceftazidine at 51.28%） and imipenem （43.59%） as well. The lowest antibiotic resistance rate of 20.51% was found to amikacin. The OXA-23 gene was identified in 17 strains of A. baumanii, and the AmpC gene in 23 strains. The TEM-1 gene was carried in 15 strains. PER-1 and SHV-2 genes were detected in two different strains. Aminoglycoside-modifying enzyme gene aac-3-1a was found in 23 strains, and the aac-6＂lb gene in 19 strains, aac-3-1a and aac-6＂lb genes hibernated in three A. baumanfi strains that showed no drug-resistant phenotype. Conclusions A. baumanii can carry multiple drug-resistant genes at the same time and result in multi-drug resistance. Aminoglycoside-modifying enzyme genes could be hibernating in aminoglycoside sensitive strains without expressing their phenotype.
基金This work was supported by grants from the National Natural Science Foundation of China （No. 30570802, No. 30800502 and No. 30801505）.
文摘Background Airway symptoms in asthma are related to decrease of epinephrine secretion, which may be ascribed to elevated nerve growth factor （NGF） in the organism. The aim of this study was to monitor the neuroendocrine alteration in the adrenal medulla of asthmatic rats. Methods Sixteen rats were randomly divided into two groups （n=-8）, control group and asthma group, and the asthmatic rats were sensitized and challenged with ovalbumin （OVA）. The levels of NGF, epinephrine and norepinephrine in serum were detected by enzyme linked immunosorbent assay （ELISA）, the NGF expression in adrenal medulla was detected by immunohistochemistry, and the changes in the ultrastructure of the adrenal medulla was observed by electron microscopy. Results The NGF expression was increased in asthmatic rats compared with control rats. Compared with control rats, the results indicated that the epinephrine level was decreased in asthmatic rats, but no significant difference was found in norepinephrine levels. We found more ganglion cells in the adrenal medulla of asthmatic rats than in control rats, with NGF immunostaining mainly located in these ganglion cells. Electron microscopic images showed the density of chromaffin granula decreased and there was shrunken nucleolemma in the adrenal medullary cells of asthmatic rats. Conclusion The innervation of the adrenal medulla is changed in asthmatic rats, and it may contribute to the epinephrine decrease in asthma.
文摘Background The extracellular release of the danger signal high mobility group box-1 （HMGB1） has been implicated in the pathogenesis and outcomes of sepsis. Understanding the mechanisms responsible for HMGB1 release can lead to the identification of targets that may inhibit this process. The transcription factor interferon regulatory factor-1 （IRF-1） is an important mediator of innate immune responses and has been shown to participate in mortality associated with endotoxemia; however, its role in mediating the release of HMGB1 in these settings is unknown. Methods Male IRF-1 knockout （KO） and age matched C57BL/6 wild type （WT） mice were given intraperitoneal （IP） injections of lipopolysaccharide （LPS）. In some experiments, 96 hours survival rates were observed. In other experiments, mice were sacrificed 12 hours after LPS administration and sera were harvested for future analysis. In in vitro study, RAW 264.7 murine monocyte/macrophage-like cells or primary peritoneal macrophage obtained from IRF-1 KO and WT mice were cultured for LPS mediated HMGB1 release analysis. And the mechanism for HMGB1 release was analyzed by immune-precipitation. Results IRF-1 KO mice experienced less mortality, and released less systemic HMGB1 compared to their WT counterparts. Exogenous administration of recombinant HMGB1 to IRF-1 KO mice returned the mortality rate to that seen originally in IRF-1 WT mice. Using cultures of peritoneal macrophages or RAW264.7 cells, in vitro LPS stimulation induced the release of HMGB1 in an IRF-1 dependent manner. And the janus associated kinase （JAK）-IRF-1 signal pathway appeared to participate in the signaling mechanisms of LPS-induced HMGB1 release by mediating acetylation of HMGBI. Conclusion IRF-1 plays a role in LPS induced release of HMGB1 and therefore may serve as a novel target in sepsis~
