Purpose Colorectal cancer is a common malignant tumor worldwide.In China,the ratio of rectal cancer to coloncancer in terms of incidence is close to 1:1.Low rectal cancer accounts for more than half of all cases of re...Purpose Colorectal cancer is a common malignant tumor worldwide.In China,the ratio of rectal cancer to coloncancer in terms of incidence is close to 1:1.Low rectal cancer accounts for more than half of all cases of rectal cancer.In recent years,the proportion of rectal cancer has trended downward,however the incidence of rectal cancer inyounger adults is increasing.The CACA Guidelines for Holistic Integrative Management of Rectal Cancer were editedto help improve the diagnosis and comprehensive treatment in China.Methods This guideline has been prepared by consensuses reached by the CACA Committee of Colorectal CancerSociety,based on a careful review of the latest evidence including China’s studies,and referred to domestic and internationalrelative guidelines,also considered China’s specific national conditions and clinical practice.Results The CACA Guidelines for Holistic Integrative Management of Rectal Cancer include the epidemiology of rectalcancer,prevention and screening,diagnosis,treatment of nonmetastatic and metastatic rectal cancer,follow-up,and whole-course rehabilitation management.Conclusion Committee of Colorectal Cancer Society,Chinese Anti-Cancer Association,standardizes the diagnosisand treatment of rectal cancer in China through the formulation of the CACA Guidelines.展开更多
Lung cancer is the most prevalent cancer in the world,and the main treatment for advanced non-small cell lung cancer is immunotherapy combined with chemotherapy.In recent years,bTMB has received increasing attention a...Lung cancer is the most prevalent cancer in the world,and the main treatment for advanced non-small cell lung cancer is immunotherapy combined with chemotherapy.In recent years,bTMB has received increasing attention as an emerging metric for monitoring the efficacy of tumour immunotherapy in terms of its operability,accessibility and real-time nature.We envisaged whether immunotherapy alone could be used to reduce the side effects of chemotherapy in patients with high bTMB lung cancer.We thus did a meta-analysis in order to show that immunotherapy alone is feasible in patients with high bTMB NSCLC.Methods This study aims to compare the efficacy of PD-1/PD-L1 inhibitors(namely,atezolizumab,pembrolizumab,nivolumab,or tislelizumab)versus chemotherapy in NSCLC patients.The search for relevant studies was conducted in three major databases(i.e.,PubMed,Embase,and Medline)up until January 2023.Specifically,we identified studies that reported risk ratios(HRs)for reporting progression-free survival(PFS)or overall survival(OS),or objective remission rates(ORs)for immunotherapy alone versus chemotherapy in high bTMB and low bTMB patient groups.Given that NSCLC represents the predominant type of lung cancer,we exclusively focused on this subtype.Our analysis encompassed a meta-analysis of the identified literature,incorporating heterogeneity analysis and sensitivity analysis.The quality of the evidence is evaluated using the Grading of Recommendations Assessment,Development and Evaluation(GRADE)approach to ascertain the reliability and robustness of the findings.Result-We conducted a meta-analysis of seven randomised controlled trials including 4,755 patients with advanced non-small cell lung cancer(NSCLC)evaluated the efficacy of PD-1 or PD-L1 monotherapy compared to chemotherapy alone.All patients were randomized to receive either PD-1/PD-L1 treatment alone or chemotherapy alone as a control.In the high bTMB patient group,PD-1/PD-L1 monotherapy resulted in significant improvements in overall survival(HR=0.55,95%CI 0.49–0.61,p=0.77)and progression-free survival(HR=0.74,95%CI 0.68–0.81,p=0.78)compared to chemotherapy alone.Conversely,in the low bTMB patient group,PD-1 monotherapy or PD-L1 monotherapy failed to demonstrate significant improvements in overall survival(HR=0.82,95%CI 0.73–0.92,p=0.13)and progression-free survival(HR=1.22,95%CI 1.22-1.45,p=0.003)in advanced NSCLC.Conclusion Our analysis suggests that monotherapy with immunotherapy is a feasible option for patients with advanced NSCLC and high bTMB.However,the results have to be construed with caution because of the small sample size and the potential bias in the studies included.Therefore,further research with larger sample sizes and rigorous study designs is necessary to confirm the observed benefits of immunotherapy in this patient population.展开更多
Background:Gene promoter methylation is a major epigenetic change in cancers,which plays critical roles in carcinogenesis.As a crucial regulator in the early stages of B-cell differentiation and embryonic neurodevelop...Background:Gene promoter methylation is a major epigenetic change in cancers,which plays critical roles in carcinogenesis.As a crucial regulator in the early stages of B-cell differentiation and embryonic neurodevelopment,the paired box 5(PAX5)gene is downregulated by methylation in several kinds of tumors and the role of this downregulation in esophageal squamous cell carcinoma(ESCC)pathogenesis remains unclear.Methods:To elucidate the role of PAX5 in ESCC,eight ESCC cell lines,51 primary ESCC tissue samples,and eight normal esophageal mucosa samples were studied and The Cancer Genome Atlas(TCGA)was queried.PAX5 expression was examined by reverse transcription-polymerase chain reaction and western blotting.Cell apoptosis,proliferation,and chemosensitivity were detected by flow cytometry,colony formation assays,and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assays in ESCC cell lines with PAX5 overexpression or silencing.Tumor xenograft models were established for in vivo verification.Results:PAX5 methylation was found in 37.3%(19/51)of primary ESCC samples,which was significantly associated with age(P=0.007)and tumor-node-metastasis stage(P=0.014).TCGA data analysis indicated that PAX5 expression was inversely correlated with promoter region methylation(r=-0.189,P=0.011 for cg00464519 and r=-0.228,P=0.002 for cg02538199).Restoration of PAX5 expression suppressed cell proliferation,promoted apoptosis,and inhibited tumor growth of ESCC cell lines,which was verified in xenografted mice.Ectopic PAX5 expression significantly increased p53 reporter luciferase activity and increased p53 messenger RNA and protein levels.A direct interaction of PAX5 with the p53 promoter region was confirmed by chromatin immunoprecipitation assays.Re-expression of PAX5 sensitized ESCC cell lines KYSE150 and KYSE30 to fluorouracil and docetaxel.Silencing of PAX5 induced resistance of KYSE450 cells to these drugs.Conclusions:As a tumor suppressor gene regulated by promoter region methylation in human ESCC,PAX5 inhibits proliferation,promotes apoptosis,and induces activation of p53 signaling.PAX5 may serve as a chemosensitive marker of ESCC.展开更多
Until the early 1990s,human cancers were considered a morphologically heterogeneous population of cells.In 1997,Bonnet et al[1] demonstrated that a small population of leukemia cells was able to differentiate in vivo ...Until the early 1990s,human cancers were considered a morphologically heterogeneous population of cells.In 1997,Bonnet et al[1] demonstrated that a small population of leukemia cells was able to differentiate in vivo into leukemic blasts,indicating that the leukemic clone was organized as a hierarchy;this was subsequently denoted as展开更多
文摘Purpose Colorectal cancer is a common malignant tumor worldwide.In China,the ratio of rectal cancer to coloncancer in terms of incidence is close to 1:1.Low rectal cancer accounts for more than half of all cases of rectal cancer.In recent years,the proportion of rectal cancer has trended downward,however the incidence of rectal cancer inyounger adults is increasing.The CACA Guidelines for Holistic Integrative Management of Rectal Cancer were editedto help improve the diagnosis and comprehensive treatment in China.Methods This guideline has been prepared by consensuses reached by the CACA Committee of Colorectal CancerSociety,based on a careful review of the latest evidence including China’s studies,and referred to domestic and internationalrelative guidelines,also considered China’s specific national conditions and clinical practice.Results The CACA Guidelines for Holistic Integrative Management of Rectal Cancer include the epidemiology of rectalcancer,prevention and screening,diagnosis,treatment of nonmetastatic and metastatic rectal cancer,follow-up,and whole-course rehabilitation management.Conclusion Committee of Colorectal Cancer Society,Chinese Anti-Cancer Association,standardizes the diagnosisand treatment of rectal cancer in China through the formulation of the CACA Guidelines.
基金supported by the Key Research and Development Project Institute of Hainan Province(ZDYF2023SHFZ117).
文摘Lung cancer is the most prevalent cancer in the world,and the main treatment for advanced non-small cell lung cancer is immunotherapy combined with chemotherapy.In recent years,bTMB has received increasing attention as an emerging metric for monitoring the efficacy of tumour immunotherapy in terms of its operability,accessibility and real-time nature.We envisaged whether immunotherapy alone could be used to reduce the side effects of chemotherapy in patients with high bTMB lung cancer.We thus did a meta-analysis in order to show that immunotherapy alone is feasible in patients with high bTMB NSCLC.Methods This study aims to compare the efficacy of PD-1/PD-L1 inhibitors(namely,atezolizumab,pembrolizumab,nivolumab,or tislelizumab)versus chemotherapy in NSCLC patients.The search for relevant studies was conducted in three major databases(i.e.,PubMed,Embase,and Medline)up until January 2023.Specifically,we identified studies that reported risk ratios(HRs)for reporting progression-free survival(PFS)or overall survival(OS),or objective remission rates(ORs)for immunotherapy alone versus chemotherapy in high bTMB and low bTMB patient groups.Given that NSCLC represents the predominant type of lung cancer,we exclusively focused on this subtype.Our analysis encompassed a meta-analysis of the identified literature,incorporating heterogeneity analysis and sensitivity analysis.The quality of the evidence is evaluated using the Grading of Recommendations Assessment,Development and Evaluation(GRADE)approach to ascertain the reliability and robustness of the findings.Result-We conducted a meta-analysis of seven randomised controlled trials including 4,755 patients with advanced non-small cell lung cancer(NSCLC)evaluated the efficacy of PD-1 or PD-L1 monotherapy compared to chemotherapy alone.All patients were randomized to receive either PD-1/PD-L1 treatment alone or chemotherapy alone as a control.In the high bTMB patient group,PD-1/PD-L1 monotherapy resulted in significant improvements in overall survival(HR=0.55,95%CI 0.49–0.61,p=0.77)and progression-free survival(HR=0.74,95%CI 0.68–0.81,p=0.78)compared to chemotherapy alone.Conversely,in the low bTMB patient group,PD-1 monotherapy or PD-L1 monotherapy failed to demonstrate significant improvements in overall survival(HR=0.82,95%CI 0.73–0.92,p=0.13)and progression-free survival(HR=1.22,95%CI 1.22-1.45,p=0.003)in advanced NSCLC.Conclusion Our analysis suggests that monotherapy with immunotherapy is a feasible option for patients with advanced NSCLC and high bTMB.However,the results have to be construed with caution because of the small sample size and the potential bias in the studies included.Therefore,further research with larger sample sizes and rigorous study designs is necessary to confirm the observed benefits of immunotherapy in this patient population.
基金National Science Foundation of China(NSFC Nos.31671298,81802390,and 81672462)Natural Science Foundation of Beijing(No.7202187)+3 种基金National Key Research and Development Program of China(Nos.2016YFC0905200,2016YFC0905302,and 2017YFC 1308900)National Geriatrics Center Funding(No.NCRCG-PLAGH-2018002)Key Projects of Clinical Application and Promotion with Capital Characteristics(No.Z161100000516003)Military Medical Special Program for Youth of Chinese People's Liberation Army General Hospital(No.QNF19037)。
文摘Background:Gene promoter methylation is a major epigenetic change in cancers,which plays critical roles in carcinogenesis.As a crucial regulator in the early stages of B-cell differentiation and embryonic neurodevelopment,the paired box 5(PAX5)gene is downregulated by methylation in several kinds of tumors and the role of this downregulation in esophageal squamous cell carcinoma(ESCC)pathogenesis remains unclear.Methods:To elucidate the role of PAX5 in ESCC,eight ESCC cell lines,51 primary ESCC tissue samples,and eight normal esophageal mucosa samples were studied and The Cancer Genome Atlas(TCGA)was queried.PAX5 expression was examined by reverse transcription-polymerase chain reaction and western blotting.Cell apoptosis,proliferation,and chemosensitivity were detected by flow cytometry,colony formation assays,and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assays in ESCC cell lines with PAX5 overexpression or silencing.Tumor xenograft models were established for in vivo verification.Results:PAX5 methylation was found in 37.3%(19/51)of primary ESCC samples,which was significantly associated with age(P=0.007)and tumor-node-metastasis stage(P=0.014).TCGA data analysis indicated that PAX5 expression was inversely correlated with promoter region methylation(r=-0.189,P=0.011 for cg00464519 and r=-0.228,P=0.002 for cg02538199).Restoration of PAX5 expression suppressed cell proliferation,promoted apoptosis,and inhibited tumor growth of ESCC cell lines,which was verified in xenografted mice.Ectopic PAX5 expression significantly increased p53 reporter luciferase activity and increased p53 messenger RNA and protein levels.A direct interaction of PAX5 with the p53 promoter region was confirmed by chromatin immunoprecipitation assays.Re-expression of PAX5 sensitized ESCC cell lines KYSE150 and KYSE30 to fluorouracil and docetaxel.Silencing of PAX5 induced resistance of KYSE450 cells to these drugs.Conclusions:As a tumor suppressor gene regulated by promoter region methylation in human ESCC,PAX5 inhibits proliferation,promotes apoptosis,and induces activation of p53 signaling.PAX5 may serve as a chemosensitive marker of ESCC.
文摘Until the early 1990s,human cancers were considered a morphologically heterogeneous population of cells.In 1997,Bonnet et al[1] demonstrated that a small population of leukemia cells was able to differentiate in vivo into leukemic blasts,indicating that the leukemic clone was organized as a hierarchy;this was subsequently denoted as
