Lung cancer is a prevalent malignancy,and fatalities of the disease exceed 400,000 cases worldwide.Lung squamous cell carcinoma(LUSC)has been recognized as the most common pathological form of lung cancer.The comprehe...Lung cancer is a prevalent malignancy,and fatalities of the disease exceed 400,000 cases worldwide.Lung squamous cell carcinoma(LUSC)has been recognized as the most common pathological form of lung cancer.The comprehensive understanding of molecular features related to LUSC progression has great significance in LUSC prognosis assessment and clinical management.In this study,we aim to identify a panel of signature genes closely associated with LUSC,which can provide novel insights into the progression of LUSC.Gene expression profiles were retrieved from public resources including gene expression omnibus(GEO)and the cancer genome atlas(TCGA)database.Differentially expressed genes(DEGs)between LUSC specimens and normal lung tissues were identified by bioinformatics analyses.A total of 66 DEGs were identified based on two cohorts of data.CytoHubba plugin of Cytoscape software was utilized for the further analyses of the top 10 candidate hub genes including OGN,ABI3BP,MAMDC2,FGF7,FAM107A,SPARCL1,DCN,COL14A1,and MFAP4 and CHRDL1,which showed significant downregulation in LUSC.Two LUSC cell lines were used to validate the functions of CHRDL1 and FAM107A through overexpression experiment.Together,our data revealed novel candidate tumor-suppressor genes in LUSC,suggesting previously unappreciated mechanisms in the progression of LUSC.展开更多
背景与目的云南东部农村地区宣威市、富源县女性居民主要从事农业生产和家务工作,基本不吸烟,但肺癌死亡率却是世界上最高的,而且发病、死亡年龄提前。本研究对宣威、富源非吸烟女性肺癌生存状况及其影响因素进行分析。方法以2006年-201...背景与目的云南东部农村地区宣威市、富源县女性居民主要从事农业生产和家务工作,基本不吸烟,但肺癌死亡率却是世界上最高的,而且发病、死亡年龄提前。本研究对宣威、富源非吸烟女性肺癌生存状况及其影响因素进行分析。方法以2006年-2010年被当地省、市、县9家医院新诊断、并纳入"非吸烟女性肺癌病例对照研究项目"的常住户籍女性肺癌病例为研究对象随访至2016年末。通过Life-table法进行全部病例生存分析,评估人群相对生存率和年龄别标化相对生存率。应用Kaplan-Meier法和Cox比例风险模型分别进行单因素生存分析、分层分析和多因素分析。结果随访的1,250例病例中,死亡1,075例,删失175例,随访中位时间为69个月(95%CI:61.9-76.0)。病例平均年龄(54.8±10.9)岁,I期、II期、III期、IV期和未知分期分别占3.5%、8.7%、20.7%、29.7%和37.4%;手术、非手术治疗和未治疗分别占17. 2%、39.0%和43. 8%,组织学、细胞学诊断占51.6%。中位生存时间13.2个月,5年观察生存率、相对生存率、年龄标化相对生存率分别为8.9%(95%CI:7.0-10.6)、9.4%(95%CI:7.6-11.5)和10.1%(95%CI:3.7-20.5)。I期、II期、III期、IV期、未分期5年生存率分别为41.1%、22.4%、5. 3%、1. 3%、11.2%;手术治疗、非手术治疗、未治疗分别为34.8%和3.2%、4.7%;腺癌、鳞癌分别为17.9%和5.6%。省级医院治疗、X线胸部筛查、非农民职业、城镇居住、65岁以下年龄等因素有利于提高生存率,而市县级医院治疗、农民职业、乡村居住、65岁以上年龄等则生存率较低。分层分析显示,任意原发灶-淋巴结-远处转移(tumornode-met a st a si s,T N M)分期,无论腺癌或鳞癌患者,行手术治疗的生存率明显高于非手术治疗;与未治疗病例相比非手术治疗仅在III期显示差异;腺癌生存率大于鳞癌不仅仅因为早期和手术病例较多,在III期、未分期也显示明显生存优势。不同级别医院治疗疗效有明显差异,省级医院治疗的IV期、鳞癌的生存预后明显优于市、县级医院。Cox分析显示治疗方法、TNM分期、治疗医院级别、X线胸部筛查是独立预后因素,其中TNM分期、手术治疗对肺癌患者生存影响较大,而治疗医院级别、X胸部筛查相对较弱。结论宣威、富源非吸烟女性肺癌生存率较低,主要与其诊断时早期病例和手术、综合治疗较少、而未治疗病例较多有关,其次较差的农村社会经济、健康保障等也是生存预后的不利因素。展开更多
Objective: Oncogenes have been shown to be drivers of non-small cell lung cancer(NSCLC), yet the tumor suppressing genes involved in lung carcinogenesis remain to be systematically investigated. This study aimed to id...Objective: Oncogenes have been shown to be drivers of non-small cell lung cancer(NSCLC), yet the tumor suppressing genes involved in lung carcinogenesis remain to be systematically investigated. This study aimed to identify tumor suppressing ubiquitin pathway genes(UPGs) that were critical to lung tumorigenesis.Methods: The 696 UPGs were silenced by an siRNA screening in NSCLC cells;the potential tumor suppressing UPGs were analyzed, and their clinical significance was investigated.Results: We reported that silencing of 11 UPGs resulted in enhanced proliferation of NSCLC cells, and four UPGs(UBL3, TRIM22, UBE2 G2, and MARCH1) were significantly downregulated in tumor samples compared to that in normal lung tissues and their expression levels were positively associated with overall survival(OS) of NSCLC patients. Among these genes, UBL3 was the most significant one. UBL3 expression was decreased in tumor samples compared to that in paired normal lung tissues in 59/86(68.6%) NSCLCs, was correlated with TNM stage and sex of NSCLC patients, and was significantly higher in non-smoking patients than in smoking patients. Silencing UBL3 accelerated cell proliferation and ectopic expression of UBL3 suppressed NSCLC in vitro and in vivo.Conclusions: These results showed that UBL3 represented a tumor suppressor in NSCLC and may have potential for use in therapeutics and for the prediction of clinical outcome of patients.展开更多
Objective:To study the M receptor blocker on inhalation in patients with overlap syndrome(chronic obstructive pulmonary disease and Obstructive sleep apnea syndrome)curative effect analysis.Methods:25 patients with ov...Objective:To study the M receptor blocker on inhalation in patients with overlap syndrome(chronic obstructive pulmonary disease and Obstructive sleep apnea syndrome)curative effect analysis.Methods:25 patients with overlap syndrome as the experimental group,chronic obstructive pulmonary disease patients(30)as control group,patients with overlap syndrome use inhaled tiotropium powder treat 30 days,to observe the changes of pulmonary function,polysomnography,and other indicators after treatment.Results:Overlap syndrome were treated by tiotropium bromide inhalation powder,has improved the pulmonary function,the sleep apnea index and lowest nocturnal oxygen saturation after treatment.Conclusion:tiotropium bromide has a preferable effective in treatment of overlap syndrome,COPD and OSAHS are interacting with each other.展开更多
OBJECTIVE To explore the application of blocking the unilateralmain pulmonary artery (MPA) in pulmonary lobectomy (PL) forpatients with stage Ⅱ and Ⅲ lung cancer, and to retrospectivelyanalyze the methods of surgery...OBJECTIVE To explore the application of blocking the unilateralmain pulmonary artery (MPA) in pulmonary lobectomy (PL) forpatients with stage Ⅱ and Ⅲ lung cancer, and to retrospectivelyanalyze the methods of surgery for blocking the unilateral mainpulmonary artery, perioperative indications, intraoperativeconcerns and postoperative cardio-pulmonary complications.METHODS During a period from January 2006 to January 2008,intra-pericardial, or extra-pericardial separation and blockade ofthe left or right MPA followed by completion of various PLs wereconducted for 30 lung cancer patients in stage-Ⅱ to Ⅲ with ill-defined anatomic structure of the pulmonary hilum and difficultpulmonary angiodiastasis.RESULTS In the 30 patients, 5 were diagnosed as stage-Ⅱb, 11stage-Ⅲa, and 14 stage-Ⅲb. During the surgery, giant tumors atthe superior pulmonary lobe, with a diameter of over 10 cm, wereseen in 13 cases, in which tumor invasion in the extra-pericardiacpulmonary artery was found in 5 cases. Hilar lymphadenectasiswith severe tumor adhesion to pulmonary blood vessel couldbe seen in 20 cases and partial tumorous invasion in thepericardium in 7. In most of the cases, adhesions existed aroundthe tumor, aorta, superior vena, and azygous vein. Invasion ofthe laryngeal and vagus nerves on the left side was found in 3cases. Of the 30 patients, simple PL was conducted in 12, andsleeve lobectomy combined with a pulmonary arterioplasty in18 cases. With a blockade of unilateral MPA, no intraoperativehemorrhea of pulmonary blood vessels occurred during surgery,when there was a clear surgical field of vision. Both PL andlymphadenectomy were smoothly completed in the 30 patients.The healthy pulmonary lobes with normal function were keptand total pneumonectomy was avoided. The time of blocking thepulmonary artery ranged from 10 to 30 min, and intraoperativeblood loss was from 200 to 300 ml. Postoperative complicatedacute pulmonary edema occurred in 5 patients and tachycardia in7 cases. Nevertheless, all patients recovered and left the hospitalafter treatment. No severe cardiopulmonary complications werefound in all patients of the group.CONCLUSION Blocking the unilateral MPA is effective todecrease the risk of intraoperative hemorrhea in the PL. It canshorten the time of surgery, improve the excision rate of lungcancer, and cut down on the rate of total pneumonectomy.展开更多
Objective:To investigate the expression level of sex-determining region Y-related high mobility group box 4(Sox4)in female lung cancer patients and its clinical significance.Methods:213cases of female lung cancer pati...Objective:To investigate the expression level of sex-determining region Y-related high mobility group box 4(Sox4)in female lung cancer patients and its clinical significance.Methods:213cases of female lung cancer patients who presented in the third affiliated hospital of Kunming medical university were selected for this study.Patients were performed radical surgery of lung cancer;the tumor and adjacent normal tissues were collected.The expression of Sox4 were determined by real-time PCR and immunohistochemical staining.The correlation between Sox4 expression and clinicopathological characteristics was analyzed.Results:The mRNA level of Sox4 was significantly higher in tumor tissues than that in adjacent normal tissues(P <0.05).The positive expression rate of SOX4 in carcinoma tissues was 54.46%,which was significantly higher than that in adjacent normal tissues(23.47%)(P <0.05).The positive expression rate of Sox4 in stageⅢ was 89.47%,which was significantly higher than that in stageⅠ-Ⅱ(P <0.05).The positive expression rate of SOX4 in lung cancer patients with lymph node metastasis was 90.91%,which was significantly higher than that in patients without lymph node metastasis(P <0.05).The positive expression rates of Sox4 in low,middle and high differentiation tissues were 69.05%,32.88% and 23.21% respectively,suggesting that the expression of Sox4 in female lung cancer tissues decreased with the increase of pathological differentiation grades.Conclusion:In female lung cancer,SOX4expression was significantly higher in tumor tissue than that of adjacent normal tissues and was correlated with clinical stage,lymph node metastasis and pathological differentiation.Sox4 expression detection may help determine the prognosis of women with lung cancer and provide a theoretical basis for molecular targeted therapy of lung cancer in women.展开更多
Ephrin type-A receptor 2(EphA2),a receptor tyrosine kinase,is overexpressed in human breast cancers often linked to poor patient prognosis.Accumulating evidence demonstrates that EphA2 plays important roles in several...Ephrin type-A receptor 2(EphA2),a receptor tyrosine kinase,is overexpressed in human breast cancers often linked to poor patient prognosis.Accumulating evidence demonstrates that EphA2 plays important roles in several critical processes associated with malignant breast progression,such as proliferation,survival,migration,invasion,drug resistance,metastasis,and angiogenesis.As its inhibition through multiple approaches can inhibit the growth of breast cancer and restore drug sensitivity,EphA2 has become a promising therapeutic target for breast cancer treatment.Here,we summarize the expression,functions,mechanisms of action,and regulation of EphA2 in breast cancer.We also list the potential therapeutic strategies targeting EphA2.Furthermore,we discuss the future directions of studying EphA2 in breast cancer.展开更多
Background:Although programmed cell death 1(PD-1)blockade plus chemotherapy can significantly prolong the progression-free survival(PFS)and overall survival(OS)in first-line settings in patients with driver-negative a...Background:Although programmed cell death 1(PD-1)blockade plus chemotherapy can significantly prolong the progression-free survival(PFS)and overall survival(OS)in first-line settings in patients with driver-negative advanced non-small-cell lung cancer(NSCLC),the predictive biomarkers remain undetermined.Here,we investigated the predictive value of tumor immune microenvironmental marker expression to characterize the response features to PD-1 blockade plus chemotherapy.Methods:Tumor tissue samples at baseline were prospectively collected from 144 locally advanced or metastatic NSCLC patients without driver gene alterations who received camrelizumab plus chemotherapy or chemotherapy alone.Tumor immune microenvironmental markers,including PD-1 ligand(PDL1),CD8,CD68,CD4 and forkhead box P3,were assessed using multiplex immunofluorescence(mIF)assays.Kaplan-Meier curveswere used to determine treatment outcome differences according to their expression status.Mutational profiles were compared between tumors with distinct expression levels of these markers and their combinations.Results:Responders had significantly higher CD8/PD-L1(P=0.015)or CD68/PD-L1 co-expression levels(P=0.021)than non-responders in the camrelizumab plus chemotherapy group,while no difference was observed in the chemotherapy group.Patients with high CD8/PD-L1 or CD68/PD-L1 co-expression level was associated with significantly longer PFS(P=0.002,P=0.024;respectively)and OS(P=0.006,P=0.026;respectively)than those with low co-expression in camrelizumab plus chemotherapy group.When comparing survival in the camrelizumab plus chemotherapy with chemotherapy by CD8/PD-L1 co-expression stratification,significantly better PFS(P=0.003)and OS(P=0.032)were observed in high co-expression subgroups.The predictive value of CD8/PD-L1 and CD68/PD-L1 co-expression remained statistically significant for PFS and OS when adjusting clinicopathological features.Although the prevalence of TP53 or KRAS mutations was similar between patients with and without CD8/PD-L1 or CD68/PD-L1 co-expression,the positive groups had a significantly higher proportion of TP53/KRAS co-mutations than the negative groups(both 13.0%vs.0.0%,P=0.023).Notably,enriched PI3K(P=0.012)and cell cycle pathway(P=0.021)were found in the CD8/PD-L1 co-expression group.Conclusion:Tumor immune microenvironmental marker expression,especially CD8/PD-L1 or CD68/PD-L1 co-expression,was associated with the efficacy of PD-1 blockade plus chemotherapy as first-line treatment in patients with advanced NSCLC.展开更多
The chromatin-based rule governing the selection and activation of replication origins remains to be elucidated.It is believed that DNA replication initiates from open chromatin domains;thus,replication origins reside...The chromatin-based rule governing the selection and activation of replication origins remains to be elucidated.It is believed that DNA replication initiates from open chromatin domains;thus,replication origins reside in open and active chromatin.However,we report here that lysine-specific demethylase 1(LSD1),which biochemically catalyzes H3K4me1/2 demethylation favoring chromatin condensation,interacts with the DNA replication machinery in human cells.We find that LSD1 level peaks in early S phase.展开更多
Although a number of studies have examined the etiology of lung cancer in Xuanwei County, China, other types of cancer in this county have not been reported systematically. This study aimed to investigate the temporal...Although a number of studies have examined the etiology of lung cancer in Xuanwei County, China, other types of cancer in this county have not been reported systematically. This study aimed to investigate the temporal trend of eight major cancers in Xuanwei County using data from three mortality surveys (1973-1975, 1990-1992, and 2004-2005). The Chinese population in 1990 was used as a standard population to calculate age- standardized mortality rates. Cancers of lung, liver, breast, brain, esophagus, leukemia, rectum, and stomach were identified as the leading cancers in this county in terms of mortality rate. During the three time periods, lung cancer remained as the most common type of cancer. The mortality rates for all other types of cancer were lower than those of the national average, but an increasing trend was observed for all the cancers, particularly from 1990-1992 to 2004-2005. The temporal trend could be party explained by changes in risk factors, but it also may be due to the improvement in cancer diagnosis and screening. Further epidemiological studies are warranted to systematically examine the underlying reasons for the temporal trend of the major cancers in Xuanwei County.展开更多
The scope and variety of the metabolic intermediates from the mitochondrial tricarboxylic acid(TCA)cycle that are engaged in epigenetic regulation of the chromatin function in the nucleus raise an outstanding question...The scope and variety of the metabolic intermediates from the mitochondrial tricarboxylic acid(TCA)cycle that are engaged in epigenetic regulation of the chromatin function in the nucleus raise an outstanding question about how timely and precise supply/consumption of these metabolites is achieved in the nucleus.We report here the identification of a nonclassical TCA cycle in the nucleus(nTCA cycle).We found that all the TCA cycle-associated enzymes including citrate synthase(CS),aconitase 2(ACO2),isocitrate dehydrogenase 3(IDH3),oxoglutarate dehydrogenase(OGDH),succinyl-CoA synthetase(SCS),fumarate hydratase(FH),and malate dehydrogenase 2(MDH2),except for succinate dehydrogenase(SDH),a component of electron transport chain for generating ATP,exist in the nucleus.We showed that these nuclear enzymes catalyze an incomplete TCA cycle similar to that found in cyanobacteria.We propose that the nTCA cycle is implemented mainly to generate/consume metabolic intermediates,not for energy production.We demonstrated that the nTCA cycle is intrinsically linked to chromatin dynamics and transcription regulation.Together,our study uncovers the existence of a nonclassical TCA cycle in the nucleus that links the metabolic pathway to epigenetic regulation.展开更多
基金Department of Science and Technology of Yunnan Province,Provincial Basic Research Program(Kunkun-Medical Joint Special Project),202101AY070001-134Yunnan Provincial Department of Science and Technology,Yunnan Provincial Gerontology Research Center,202102AA310069Yunnan Provincial Department of Science and Technology-Kunming Medical University Basic Research Joint Special Key Project,202201AY070001-136.
文摘Lung cancer is a prevalent malignancy,and fatalities of the disease exceed 400,000 cases worldwide.Lung squamous cell carcinoma(LUSC)has been recognized as the most common pathological form of lung cancer.The comprehensive understanding of molecular features related to LUSC progression has great significance in LUSC prognosis assessment and clinical management.In this study,we aim to identify a panel of signature genes closely associated with LUSC,which can provide novel insights into the progression of LUSC.Gene expression profiles were retrieved from public resources including gene expression omnibus(GEO)and the cancer genome atlas(TCGA)database.Differentially expressed genes(DEGs)between LUSC specimens and normal lung tissues were identified by bioinformatics analyses.A total of 66 DEGs were identified based on two cohorts of data.CytoHubba plugin of Cytoscape software was utilized for the further analyses of the top 10 candidate hub genes including OGN,ABI3BP,MAMDC2,FGF7,FAM107A,SPARCL1,DCN,COL14A1,and MFAP4 and CHRDL1,which showed significant downregulation in LUSC.Two LUSC cell lines were used to validate the functions of CHRDL1 and FAM107A through overexpression experiment.Together,our data revealed novel candidate tumor-suppressor genes in LUSC,suggesting previously unappreciated mechanisms in the progression of LUSC.
文摘背景与目的云南东部农村地区宣威市、富源县女性居民主要从事农业生产和家务工作,基本不吸烟,但肺癌死亡率却是世界上最高的,而且发病、死亡年龄提前。本研究对宣威、富源非吸烟女性肺癌生存状况及其影响因素进行分析。方法以2006年-2010年被当地省、市、县9家医院新诊断、并纳入"非吸烟女性肺癌病例对照研究项目"的常住户籍女性肺癌病例为研究对象随访至2016年末。通过Life-table法进行全部病例生存分析,评估人群相对生存率和年龄别标化相对生存率。应用Kaplan-Meier法和Cox比例风险模型分别进行单因素生存分析、分层分析和多因素分析。结果随访的1,250例病例中,死亡1,075例,删失175例,随访中位时间为69个月(95%CI:61.9-76.0)。病例平均年龄(54.8±10.9)岁,I期、II期、III期、IV期和未知分期分别占3.5%、8.7%、20.7%、29.7%和37.4%;手术、非手术治疗和未治疗分别占17. 2%、39.0%和43. 8%,组织学、细胞学诊断占51.6%。中位生存时间13.2个月,5年观察生存率、相对生存率、年龄标化相对生存率分别为8.9%(95%CI:7.0-10.6)、9.4%(95%CI:7.6-11.5)和10.1%(95%CI:3.7-20.5)。I期、II期、III期、IV期、未分期5年生存率分别为41.1%、22.4%、5. 3%、1. 3%、11.2%;手术治疗、非手术治疗、未治疗分别为34.8%和3.2%、4.7%;腺癌、鳞癌分别为17.9%和5.6%。省级医院治疗、X线胸部筛查、非农民职业、城镇居住、65岁以下年龄等因素有利于提高生存率,而市县级医院治疗、农民职业、乡村居住、65岁以上年龄等则生存率较低。分层分析显示,任意原发灶-淋巴结-远处转移(tumornode-met a st a si s,T N M)分期,无论腺癌或鳞癌患者,行手术治疗的生存率明显高于非手术治疗;与未治疗病例相比非手术治疗仅在III期显示差异;腺癌生存率大于鳞癌不仅仅因为早期和手术病例较多,在III期、未分期也显示明显生存优势。不同级别医院治疗疗效有明显差异,省级医院治疗的IV期、鳞癌的生存预后明显优于市、县级医院。Cox分析显示治疗方法、TNM分期、治疗医院级别、X线胸部筛查是独立预后因素,其中TNM分期、手术治疗对肺癌患者生存影响较大,而治疗医院级别、X胸部筛查相对较弱。结论宣威、富源非吸烟女性肺癌生存率较低,主要与其诊断时早期病例和手术、综合治疗较少、而未治疗病例较多有关,其次较差的农村社会经济、健康保障等也是生存预后的不利因素。
基金supported by the National Key Research and Development Program of China (Grant No. 2016YFC0905501)the National Natural Science Funds for Distinguished Young Scholar (Grant No. 81425025)+3 种基金the Key Project of the National Natural Science Foundation of China (Grant No. 81830093)the CAMS Innovation Fund for Medical Sciences (Grant No. CIFMS2019-I2M-1-003)the National Natural Science Foundation of China (Grant No. 81672765 and 81802796)。
文摘Objective: Oncogenes have been shown to be drivers of non-small cell lung cancer(NSCLC), yet the tumor suppressing genes involved in lung carcinogenesis remain to be systematically investigated. This study aimed to identify tumor suppressing ubiquitin pathway genes(UPGs) that were critical to lung tumorigenesis.Methods: The 696 UPGs were silenced by an siRNA screening in NSCLC cells;the potential tumor suppressing UPGs were analyzed, and their clinical significance was investigated.Results: We reported that silencing of 11 UPGs resulted in enhanced proliferation of NSCLC cells, and four UPGs(UBL3, TRIM22, UBE2 G2, and MARCH1) were significantly downregulated in tumor samples compared to that in normal lung tissues and their expression levels were positively associated with overall survival(OS) of NSCLC patients. Among these genes, UBL3 was the most significant one. UBL3 expression was decreased in tumor samples compared to that in paired normal lung tissues in 59/86(68.6%) NSCLCs, was correlated with TNM stage and sex of NSCLC patients, and was significantly higher in non-smoking patients than in smoking patients. Silencing UBL3 accelerated cell proliferation and ectopic expression of UBL3 suppressed NSCLC in vitro and in vivo.Conclusions: These results showed that UBL3 represented a tumor suppressor in NSCLC and may have potential for use in therapeutics and for the prediction of clinical outcome of patients.
文摘Objective:To study the M receptor blocker on inhalation in patients with overlap syndrome(chronic obstructive pulmonary disease and Obstructive sleep apnea syndrome)curative effect analysis.Methods:25 patients with overlap syndrome as the experimental group,chronic obstructive pulmonary disease patients(30)as control group,patients with overlap syndrome use inhaled tiotropium powder treat 30 days,to observe the changes of pulmonary function,polysomnography,and other indicators after treatment.Results:Overlap syndrome were treated by tiotropium bromide inhalation powder,has improved the pulmonary function,the sleep apnea index and lowest nocturnal oxygen saturation after treatment.Conclusion:tiotropium bromide has a preferable effective in treatment of overlap syndrome,COPD and OSAHS are interacting with each other.
文摘OBJECTIVE To explore the application of blocking the unilateralmain pulmonary artery (MPA) in pulmonary lobectomy (PL) forpatients with stage Ⅱ and Ⅲ lung cancer, and to retrospectivelyanalyze the methods of surgery for blocking the unilateral mainpulmonary artery, perioperative indications, intraoperativeconcerns and postoperative cardio-pulmonary complications.METHODS During a period from January 2006 to January 2008,intra-pericardial, or extra-pericardial separation and blockade ofthe left or right MPA followed by completion of various PLs wereconducted for 30 lung cancer patients in stage-Ⅱ to Ⅲ with ill-defined anatomic structure of the pulmonary hilum and difficultpulmonary angiodiastasis.RESULTS In the 30 patients, 5 were diagnosed as stage-Ⅱb, 11stage-Ⅲa, and 14 stage-Ⅲb. During the surgery, giant tumors atthe superior pulmonary lobe, with a diameter of over 10 cm, wereseen in 13 cases, in which tumor invasion in the extra-pericardiacpulmonary artery was found in 5 cases. Hilar lymphadenectasiswith severe tumor adhesion to pulmonary blood vessel couldbe seen in 20 cases and partial tumorous invasion in thepericardium in 7. In most of the cases, adhesions existed aroundthe tumor, aorta, superior vena, and azygous vein. Invasion ofthe laryngeal and vagus nerves on the left side was found in 3cases. Of the 30 patients, simple PL was conducted in 12, andsleeve lobectomy combined with a pulmonary arterioplasty in18 cases. With a blockade of unilateral MPA, no intraoperativehemorrhea of pulmonary blood vessels occurred during surgery,when there was a clear surgical field of vision. Both PL andlymphadenectomy were smoothly completed in the 30 patients.The healthy pulmonary lobes with normal function were keptand total pneumonectomy was avoided. The time of blocking thepulmonary artery ranged from 10 to 30 min, and intraoperativeblood loss was from 200 to 300 ml. Postoperative complicatedacute pulmonary edema occurred in 5 patients and tachycardia in7 cases. Nevertheless, all patients recovered and left the hospitalafter treatment. No severe cardiopulmonary complications werefound in all patients of the group.CONCLUSION Blocking the unilateral MPA is effective todecrease the risk of intraoperative hemorrhea in the PL. It canshorten the time of surgery, improve the excision rate of lungcancer, and cut down on the rate of total pneumonectomy.
基金supported by grants from the Fund for Less Developed Regions of the National Natural Science Foundation of China(No.81460441)the Scientific Research Fund for Key Projects of Yunnan Education Department(No.2013Z110)Special Joint Fund of Yunnan Provincial Science & Technology Bureau-Kunming Medical College(No.2013FB132)
文摘Objective:To investigate the expression level of sex-determining region Y-related high mobility group box 4(Sox4)in female lung cancer patients and its clinical significance.Methods:213cases of female lung cancer patients who presented in the third affiliated hospital of Kunming medical university were selected for this study.Patients were performed radical surgery of lung cancer;the tumor and adjacent normal tissues were collected.The expression of Sox4 were determined by real-time PCR and immunohistochemical staining.The correlation between Sox4 expression and clinicopathological characteristics was analyzed.Results:The mRNA level of Sox4 was significantly higher in tumor tissues than that in adjacent normal tissues(P <0.05).The positive expression rate of SOX4 in carcinoma tissues was 54.46%,which was significantly higher than that in adjacent normal tissues(23.47%)(P <0.05).The positive expression rate of Sox4 in stageⅢ was 89.47%,which was significantly higher than that in stageⅠ-Ⅱ(P <0.05).The positive expression rate of SOX4 in lung cancer patients with lymph node metastasis was 90.91%,which was significantly higher than that in patients without lymph node metastasis(P <0.05).The positive expression rates of Sox4 in low,middle and high differentiation tissues were 69.05%,32.88% and 23.21% respectively,suggesting that the expression of Sox4 in female lung cancer tissues decreased with the increase of pathological differentiation grades.Conclusion:In female lung cancer,SOX4expression was significantly higher in tumor tissue than that of adjacent normal tissues and was correlated with clinical stage,lymph node metastasis and pathological differentiation.Sox4 expression detection may help determine the prognosis of women with lung cancer and provide a theoretical basis for molecular targeted therapy of lung cancer in women.
基金supported by the Beijing Nova Program(Z201100006820069)National Key R&D Program of China(2016YFC0901400,2016YFC0901404,and 2018YFC1311706)CAMS Innovation Fund for Medical Sciences(CIFMS)(2018-I2M3-003 and 2021-I2M-1-011)。
基金supported by the National Key Research and Development Program of China(2020YFA0112300 to C.Chen,2017YFC0907902 to Y.Huang)National Natural Science Foundation of China(81830087 and 31771516 to C.Chen+4 种基金81802671 and81872414 to D.Jiang)Yunnan Fundamental Research Projects(2019FB112 and 202001AW070018 to D.Jiang202001AY070001-238 to P.Zhao)Education Department Scientific Research Fund of Yunnan Province(2020J0204 to P.Zhao)Project of Innovative Research Team of Yunnan Province(2019HC005)。
文摘Ephrin type-A receptor 2(EphA2),a receptor tyrosine kinase,is overexpressed in human breast cancers often linked to poor patient prognosis.Accumulating evidence demonstrates that EphA2 plays important roles in several critical processes associated with malignant breast progression,such as proliferation,survival,migration,invasion,drug resistance,metastasis,and angiogenesis.As its inhibition through multiple approaches can inhibit the growth of breast cancer and restore drug sensitivity,EphA2 has become a promising therapeutic target for breast cancer treatment.Here,we summarize the expression,functions,mechanisms of action,and regulation of EphA2 in breast cancer.We also list the potential therapeutic strategies targeting EphA2.Furthermore,we discuss the future directions of studying EphA2 in breast cancer.
基金supported in part by grants from the National Natural Science Foundation of China(No.81871865,81874036,81972167 and 82102859)the Backbone Program of Shanghai Pulmonary Hospital(No.FKGG1802)+4 种基金Shanghai Pujiang Talent Plan(No.2019PJD048)Shanghai Science and Technology Committee Foundation(NO.19411950300)Shanghai Key disciplines of Respiratory(No.2017ZZ02012)Oncology development incentive program of Shanghai Pulmonary Hospital,Shanghai Multidisciplinary Cooperative Project for Diagnosis and Treatment of Major DiseasesKey Clinical Project Development Program of Shanghai.
文摘Background:Although programmed cell death 1(PD-1)blockade plus chemotherapy can significantly prolong the progression-free survival(PFS)and overall survival(OS)in first-line settings in patients with driver-negative advanced non-small-cell lung cancer(NSCLC),the predictive biomarkers remain undetermined.Here,we investigated the predictive value of tumor immune microenvironmental marker expression to characterize the response features to PD-1 blockade plus chemotherapy.Methods:Tumor tissue samples at baseline were prospectively collected from 144 locally advanced or metastatic NSCLC patients without driver gene alterations who received camrelizumab plus chemotherapy or chemotherapy alone.Tumor immune microenvironmental markers,including PD-1 ligand(PDL1),CD8,CD68,CD4 and forkhead box P3,were assessed using multiplex immunofluorescence(mIF)assays.Kaplan-Meier curveswere used to determine treatment outcome differences according to their expression status.Mutational profiles were compared between tumors with distinct expression levels of these markers and their combinations.Results:Responders had significantly higher CD8/PD-L1(P=0.015)or CD68/PD-L1 co-expression levels(P=0.021)than non-responders in the camrelizumab plus chemotherapy group,while no difference was observed in the chemotherapy group.Patients with high CD8/PD-L1 or CD68/PD-L1 co-expression level was associated with significantly longer PFS(P=0.002,P=0.024;respectively)and OS(P=0.006,P=0.026;respectively)than those with low co-expression in camrelizumab plus chemotherapy group.When comparing survival in the camrelizumab plus chemotherapy with chemotherapy by CD8/PD-L1 co-expression stratification,significantly better PFS(P=0.003)and OS(P=0.032)were observed in high co-expression subgroups.The predictive value of CD8/PD-L1 and CD68/PD-L1 co-expression remained statistically significant for PFS and OS when adjusting clinicopathological features.Although the prevalence of TP53 or KRAS mutations was similar between patients with and without CD8/PD-L1 or CD68/PD-L1 co-expression,the positive groups had a significantly higher proportion of TP53/KRAS co-mutations than the negative groups(both 13.0%vs.0.0%,P=0.023).Notably,enriched PI3K(P=0.012)and cell cycle pathway(P=0.021)were found in the CD8/PD-L1 co-expression group.Conclusion:Tumor immune microenvironmental marker expression,especially CD8/PD-L1 or CD68/PD-L1 co-expression,was associated with the efficacy of PD-1 blockade plus chemotherapy as first-line treatment in patients with advanced NSCLC.
基金This work was supported by grants(2021YFA1300603 to Y.S.and 2019YFA0508904 to J.L.)from the Ministry of Science and Technology of China(82188102,81730079,and 31991164 to Y.S.and 31371372 and 81874154 to X.Y.)from the National Natural Science Foundation of China,and the Canadian Institutes of Health Research(MOP79368 and FDN-159913 to G.W.B.).We thank Tina L.Sing,David Gallo,and Brandon Ho of the Brown lab for assistance with flow cytometry analysis and with DNA fiber assays.
文摘The chromatin-based rule governing the selection and activation of replication origins remains to be elucidated.It is believed that DNA replication initiates from open chromatin domains;thus,replication origins reside in open and active chromatin.However,we report here that lysine-specific demethylase 1(LSD1),which biochemically catalyzes H3K4me1/2 demethylation favoring chromatin condensation,interacts with the DNA replication machinery in human cells.We find that LSD1 level peaks in early S phase.
文摘Although a number of studies have examined the etiology of lung cancer in Xuanwei County, China, other types of cancer in this county have not been reported systematically. This study aimed to investigate the temporal trend of eight major cancers in Xuanwei County using data from three mortality surveys (1973-1975, 1990-1992, and 2004-2005). The Chinese population in 1990 was used as a standard population to calculate age- standardized mortality rates. Cancers of lung, liver, breast, brain, esophagus, leukemia, rectum, and stomach were identified as the leading cancers in this county in terms of mortality rate. During the three time periods, lung cancer remained as the most common type of cancer. The mortality rates for all other types of cancer were lower than those of the national average, but an increasing trend was observed for all the cancers, particularly from 1990-1992 to 2004-2005. The temporal trend could be party explained by changes in risk factors, but it also may be due to the improvement in cancer diagnosis and screening. Further epidemiological studies are warranted to systematically examine the underlying reasons for the temporal trend of the major cancers in Xuanwei County.
基金This work was supported by a grant(2016YFC1302304 to Y.S.)from the Ministry of Science and Technology of Chinaa grant(Z200020 to L.S.)from the Natural Science Foundation of Beijing+1 种基金a grant(QNBJ2020-2 to L.S.)from National Program for Support of Top-notch Young Professionalsgrants(81530073 and 81730079 to Y.S.,31571340 and 81874158 to L.S.,81972659 to W.S.)from the National Natural Science Foundation of China.
文摘The scope and variety of the metabolic intermediates from the mitochondrial tricarboxylic acid(TCA)cycle that are engaged in epigenetic regulation of the chromatin function in the nucleus raise an outstanding question about how timely and precise supply/consumption of these metabolites is achieved in the nucleus.We report here the identification of a nonclassical TCA cycle in the nucleus(nTCA cycle).We found that all the TCA cycle-associated enzymes including citrate synthase(CS),aconitase 2(ACO2),isocitrate dehydrogenase 3(IDH3),oxoglutarate dehydrogenase(OGDH),succinyl-CoA synthetase(SCS),fumarate hydratase(FH),and malate dehydrogenase 2(MDH2),except for succinate dehydrogenase(SDH),a component of electron transport chain for generating ATP,exist in the nucleus.We showed that these nuclear enzymes catalyze an incomplete TCA cycle similar to that found in cyanobacteria.We propose that the nTCA cycle is implemented mainly to generate/consume metabolic intermediates,not for energy production.We demonstrated that the nTCA cycle is intrinsically linked to chromatin dynamics and transcription regulation.Together,our study uncovers the existence of a nonclassical TCA cycle in the nucleus that links the metabolic pathway to epigenetic regulation.