Objective: Long non-coding RNAs(lnc RNAs) are involved in numerous biological processes in lung cancer cells. In our previous studies, we identified a lnc RNA, ENST00000439577, which is highly expressed in lung carcin...Objective: Long non-coding RNAs(lnc RNAs) are involved in numerous biological processes in lung cancer cells. In our previous studies, we identified a lnc RNA, ENST00000439577, which is highly expressed in lung carcinomas, and termed it lung cancer progression-associated transcript 1(LCPAT1). To characterize the role of LCPAT1 in lung cancer, we conducted the current study.Methods: Expression of LCPAT1 and autophagy-associated markers in tumor tissues and lung cancer cell lines was determined by real-time quantitative polymerase chain reaction(q PCR). Hematoxylin and eosin(HE) staining, q PCR, Western blot, and immunohistochemistry were performed to evaluate xenografted tumor tissues. Autophagy induced by rapamycin was detected by Western blot and immunofluorescence in lung cancer cell lines.Results: Expression of LCPAT1 and microtubule-associated protein 1 light chain 3 beta(LC3B) was positively correlated in lung cancer. Knockdown of LCPAT1 inhibited tumor growth and suppressed cell autophagy in vivo. Moreover, LCPAT1 knockdown in lung cancer cell lines resulted in decreased autophagy-associated gene expression and alleviated the cell autophagy induced by rapamycin.Conclusions: We speculate that LCPAT1 plays a crucial role in regulating autophagy in lung cancer.展开更多
Objective:Recent research has indicated that altered promoter methylation of oncogenes and tumor suppressor genes is an important mechanism in lung cancer development and progression.In this study,we investigated the ...Objective:Recent research has indicated that altered promoter methylation of oncogenes and tumor suppressor genes is an important mechanism in lung cancer development and progression.In this study,we investigated the association between promoter methylation of TMEM88,a possible inhibitor of the Wnt/β-Catenin signaling,and the survival of patients with nonsmall cell lung cancer(NSCLC).Methods:Twelve pairs of tumor and adjacent non-tumor samples were used for microarray analyses of DNA methylation and gene expression.For validation,more than two hundred additional samples were analyzed for methylation using bisulfite pyrosequencing and for gene expression using q RT-PCR.Then the cell function were tested by wound healing,transwell,CCK8 and cell cycle assay.Results:Our analysis of patient specimens showed that TMEM88 methylation was higher in NSCLC tumors(82.2%±10.3,P<0.01)compared with the adjacent normal tissues(65.9%±7.2).The survival analysis revealed that patients with high TMEM88methylation had a shorter overall survival(46 months)compared with patients with low TMEM88 methylation(>56 months;P=0.021).In addition,we found that demethylation treatment could inhibit tumor cell proliferation,migration,and invasion,which was supportive of an association between methylation and survival.Conclusions:Based on these consistent observations,we concluded that TMEM88 may play an important role in NSCLC progression and that promoter methylation of TMEM88 may serve as a biomarker for NSCLC prognosis and treatment.展开更多
Background There is insufficient evidence to provide recommendations for leisure-time physical activity among workers across various occupational physical activity levels.This study aimed to assess the association of ...Background There is insufficient evidence to provide recommendations for leisure-time physical activity among workers across various occupational physical activity levels.This study aimed to assess the association of leisure-time physical activity with cardiovascular and all-cause mortality across occupational physical activity levels.Methods This study utilized individual participant data from 21 cohort studies,comprising both published and unpublished data.Eligibility criteria included individual-level data on leisure-time and occupational physical activity(categorized as sedentary,low,moderate,and high)along with data on all-cause and/or cardiovascular mortality.A 2-stage individual participant data meta-analysis was conducted,with separate analysis of each study using Cox proportional hazards models(Stage 1).These results were combined using random-effects models(Stage 2).Results Higher leisure-time physical activity levels were associated with lower all-cause and cardiovascular mortality risk across most occupational physical activity levels,for both males and females.Among males with sedentary work,high compared to sedentary leisure-time physical activity was associated with lower all-cause(hazard ratios(HR)=0.77,95%confidence interval(95%CI):0.70-0.85)and cardiovascular mortality(HR=0.76,95%CI:0.66-0.87)risk.Among males with high levels of occupational physical activity,high compared to sedentary leisure-time physical activity was associated with lower all-cause(HR=0.84,95%CI:0.74-0.97)and cardiovascular mortality(HR=0.79,95%CI:0.60-1.04)risk,while HRs for low and moderate levels of leisure-time physical activity ranged between 0.87 and 0.97 and were not statistically significant.Among females,most effects were similar but more imprecise,especially in the higher occupational physical activity levels.Conclusion Higher levels of leisure-time physical activity were generally associated with lower mortality risks.However,results for workers with moderate and high occupational physical activity levels,especially women,were more imprecise.Our findings suggests that workers may benefit from engaging in high levels of leisure-time physical activity,irrespective of their level of occupational physical activity.展开更多
Helicobacter pylori(H. pylori) infection is a wellestablished risk factor for the development of gastric cancer(GC), one of the most common and deadliest neoplasms worldwide. H. pylori infection induces chronic inflam...Helicobacter pylori(H. pylori) infection is a wellestablished risk factor for the development of gastric cancer(GC), one of the most common and deadliest neoplasms worldwide. H. pylori infection induces chronic inflammation in the gastric mucosa that, in the absence of treatment, may progress through a series of steps to GC. GC is only one of several clinical outcomes associated with this bacterial infection, which may be at least partially attributed to the high genetic variability of H. pylori. The biological mechanisms underlying how and under what circumstances H. pylori alters normal physiological processes remain enigmatic. A key aspect of carcinogenesis is the acquisition of traits that equip preneoplastic cells with the ability to invade. Accumulating evidence implicates H. pylori in the manipulation of cellular and molecular programs that are crucial for conferring cells with invasive capabilities. We present here an overview of the main findings about the involvement of H. pylori in the acquisition of cell invasive behavior, specifically focusing on the epithelial-to-mesenchymal transition, changes in cell polarity, and deregulation of molecules that control extracellular matrix remodeling.展开更多
Owing to shared risk factors between cardiometabolic diseases(CMDs)and cancer,coupled with population aging,the lifetime risk of an individual developing cancer after a CMD is increasing.Furthermore,biological mechani...Owing to shared risk factors between cardiometabolic diseases(CMDs)and cancer,coupled with population aging,the lifetime risk of an individual developing cancer after a CMD is increasing.Furthermore,biological mechanisms such as insulin resistance or inflammation may not only predispose individuals withCMDto an elevated risk of certain types of cancer but also to a diagnosis of cancer at an advanced stage[1,2].展开更多
Recent epidemiological studies have suggested a positive association between ultra-processed food consumption and breast cancer risk,although some studies also reported no association.Furthermore,the evidence regardin...Recent epidemiological studies have suggested a positive association between ultra-processed food consumption and breast cancer risk,although some studies also reported no association.Furthermore,the evidence regarding the associations between intake of food with lower degrees of processing and breast cancer risk is limited.Thus,we investigated the associations between dietary intake by degree of food processing and breast cancer risk,overall and by breast cancer subtypes in the European Prospective Investigation into Cancer and Nutrition(EPIC)study.Dietary intake of EPIC participants was assessed via questionnaires at baseline.More than 11,000 food ingredients were classified into four groups of food processing levels using the NOVA classification system:unprocessed/minimally processed(NOVA 1),culinary ingredients(NOVA 2),processed(NOVA 3)and ultra-processed(NOVA 4).Cox proportional hazards models were used to estimate hazard ratios(HRs)and 95%confidence intervals(CIs)of breast cancer per standard deviation increase in daily consumption(grams)of foods from each NOVA group.The current analysis included 14,933 breast cancer cases,diagnosed among the 318,686 EPIC female participants,(median follow-up of 14.9 years).No associations were found between breast cancer risk and the level of dietary intake from NOVA 1[HR_(per 1 SD)=0.99(95%CI 0.97-1.01)],NOVA 2[HR_(per 1 SD)=1.01(95%CI 0.98-1.03)]and NOVA 4[HR_(per 1 SD)=1.01(95%CI 0.99-1.03)]foods.However,a positive association was found between NOVA 3 and breast cancer risk[HR_(per 1 SD)=1.05(95%CI 1.03-1.07)]which became non-significant after adjustment for alcohol intake[HR_(per 1 SD)=1.01(95%CI 0.98-1.05)]or when beer and wine were excluded from this group[HR_(per 1 SD)=0.99(95%CI 0.97-1.01)].The associations did not differ by breast cancer subtype,menopausal status or body mass index.Findings from this large-scale prospective study suggest that the positive association between processed food intake and breast cancer risk was likely driven by alcoholic beverage consumption.展开更多
Dear Editor,In the European region,which shares 22.8%of the global cancer burden for 10%of the global population,there were around 4.4 million new cancer cases and 1.9 million deaths from cancer in 2020[1].The reasons...Dear Editor,In the European region,which shares 22.8%of the global cancer burden for 10%of the global population,there were around 4.4 million new cancer cases and 1.9 million deaths from cancer in 2020[1].The reasons for the high cancer incidence rates are complex;however,diet and dietary components are among the main contributors to cancer risk[2].In modern-day living,a growing proportion of people include in their diets ultra-processed foods.Byproducts of food processing and home-prepared foods are so-called dietary advanced glycation endproducts(AGEs),which are reactive metabolites emerging during the breakdown of reducing sugar.AGEs production is preponderant in dry high-heat processes(e.g.,baking,roasting);hence foods such as cakes,crisps,crackers,cereal products,meat and meat-derived products represent a major source of dietary AGEs[3].展开更多
The tumor microenvironment represents a dynamic and multifaceted milieu characterized by the complex interactions of diverse cellular and non-cellular constituents.1,2 These constituents include tumor cells,microorgan...The tumor microenvironment represents a dynamic and multifaceted milieu characterized by the complex interactions of diverse cellular and non-cellular constituents.1,2 These constituents include tumor cells,microorganisms,immune and other stromal cells,and extracellular matrices.The orchestration of these components intricately contributes to tumor evolution and shapes responses to cancer treatment(Figure 1).A better understanding of the tumor microenvironment is critical to elucidate the etiology of cancer and develop more efficient therapeutic strategies.展开更多
基金funded by the National Natural Science Foundation of China (Grant No. 81401046 and No.21777099)Shanghai Jiao Tong University Interdisciplinary Research Key Grant (Grant No. YG2015ZD01)Shanghai Jiao Tong University "New Young Teachers Startup Plan"
文摘Objective: Long non-coding RNAs(lnc RNAs) are involved in numerous biological processes in lung cancer cells. In our previous studies, we identified a lnc RNA, ENST00000439577, which is highly expressed in lung carcinomas, and termed it lung cancer progression-associated transcript 1(LCPAT1). To characterize the role of LCPAT1 in lung cancer, we conducted the current study.Methods: Expression of LCPAT1 and autophagy-associated markers in tumor tissues and lung cancer cell lines was determined by real-time quantitative polymerase chain reaction(q PCR). Hematoxylin and eosin(HE) staining, q PCR, Western blot, and immunohistochemistry were performed to evaluate xenografted tumor tissues. Autophagy induced by rapamycin was detected by Western blot and immunofluorescence in lung cancer cell lines.Results: Expression of LCPAT1 and microtubule-associated protein 1 light chain 3 beta(LC3B) was positively correlated in lung cancer. Knockdown of LCPAT1 inhibited tumor growth and suppressed cell autophagy in vivo. Moreover, LCPAT1 knockdown in lung cancer cell lines resulted in decreased autophagy-associated gene expression and alleviated the cell autophagy induced by rapamycin.Conclusions: We speculate that LCPAT1 plays a crucial role in regulating autophagy in lung cancer.
基金supported by the National Natural Science Foundation of China(Grant No.81573231)the Medical Professionals Crossing Project of Shanghai Jiao Tong University(Grant No.YG2015ZD01)
文摘Objective:Recent research has indicated that altered promoter methylation of oncogenes and tumor suppressor genes is an important mechanism in lung cancer development and progression.In this study,we investigated the association between promoter methylation of TMEM88,a possible inhibitor of the Wnt/β-Catenin signaling,and the survival of patients with nonsmall cell lung cancer(NSCLC).Methods:Twelve pairs of tumor and adjacent non-tumor samples were used for microarray analyses of DNA methylation and gene expression.For validation,more than two hundred additional samples were analyzed for methylation using bisulfite pyrosequencing and for gene expression using q RT-PCR.Then the cell function were tested by wound healing,transwell,CCK8 and cell cycle assay.Results:Our analysis of patient specimens showed that TMEM88 methylation was higher in NSCLC tumors(82.2%±10.3,P<0.01)compared with the adjacent normal tissues(65.9%±7.2).The survival analysis revealed that patients with high TMEM88methylation had a shorter overall survival(46 months)compared with patients with low TMEM88 methylation(>56 months;P=0.021).In addition,we found that demethylation treatment could inhibit tumor cell proliferation,migration,and invasion,which was supportive of an association between methylation and survival.Conclusions:Based on these consistent observations,we concluded that TMEM88 may play an important role in NSCLC progression and that promoter methylation of TMEM88 may serve as a biomarker for NSCLC prognosis and treatment.
基金The Trùndelag Health Study (HUNT) is a collaboration between HUNT Research Centre (Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology), Trùndelag County Council, Central Norway Regional Health Authority, and the Norwegian Institute of Public HealthThe coordination of European Prospective Investigation into Cancer and Nutrition - Spain study (EPIC) is financially supported by the International Agency for Research on Cancer (IARC)+7 种基金by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC)supported by Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII), Regional Governments of Andaluc 1a, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology - ICO (Spain)funded by The Netherlands Organisation for Health Research and DevelopmentZon Mw (Grant No.: 531-00141-3)Funding for the SHIP study has been provided by the Federal Ministry for Education and Research (BMBFidentification codes 01 ZZ96030, 01 ZZ0103, and 01 ZZ0701)support from the Swedish Research Council (2018-02527 and 2019-00193)financed by the Helmholtz Zentrum München - German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research (BMBF) and by the State of Bavaria.
文摘Background There is insufficient evidence to provide recommendations for leisure-time physical activity among workers across various occupational physical activity levels.This study aimed to assess the association of leisure-time physical activity with cardiovascular and all-cause mortality across occupational physical activity levels.Methods This study utilized individual participant data from 21 cohort studies,comprising both published and unpublished data.Eligibility criteria included individual-level data on leisure-time and occupational physical activity(categorized as sedentary,low,moderate,and high)along with data on all-cause and/or cardiovascular mortality.A 2-stage individual participant data meta-analysis was conducted,with separate analysis of each study using Cox proportional hazards models(Stage 1).These results were combined using random-effects models(Stage 2).Results Higher leisure-time physical activity levels were associated with lower all-cause and cardiovascular mortality risk across most occupational physical activity levels,for both males and females.Among males with sedentary work,high compared to sedentary leisure-time physical activity was associated with lower all-cause(hazard ratios(HR)=0.77,95%confidence interval(95%CI):0.70-0.85)and cardiovascular mortality(HR=0.76,95%CI:0.66-0.87)risk.Among males with high levels of occupational physical activity,high compared to sedentary leisure-time physical activity was associated with lower all-cause(HR=0.84,95%CI:0.74-0.97)and cardiovascular mortality(HR=0.79,95%CI:0.60-1.04)risk,while HRs for low and moderate levels of leisure-time physical activity ranged between 0.87 and 0.97 and were not statistically significant.Among females,most effects were similar but more imprecise,especially in the higher occupational physical activity levels.Conclusion Higher levels of leisure-time physical activity were generally associated with lower mortality risks.However,results for workers with moderate and high occupational physical activity levels,especially women,were more imprecise.Our findings suggests that workers may benefit from engaging in high levels of leisure-time physical activity,irrespective of their level of occupational physical activity.
基金Supported by Vicerrectoría de Investigación of the University of Costa Rica,No.B6A11,No.B7281 and No.90912
文摘Helicobacter pylori(H. pylori) infection is a wellestablished risk factor for the development of gastric cancer(GC), one of the most common and deadliest neoplasms worldwide. H. pylori infection induces chronic inflammation in the gastric mucosa that, in the absence of treatment, may progress through a series of steps to GC. GC is only one of several clinical outcomes associated with this bacterial infection, which may be at least partially attributed to the high genetic variability of H. pylori. The biological mechanisms underlying how and under what circumstances H. pylori alters normal physiological processes remain enigmatic. A key aspect of carcinogenesis is the acquisition of traits that equip preneoplastic cells with the ability to invade. Accumulating evidence implicates H. pylori in the manipulation of cellular and molecular programs that are crucial for conferring cells with invasive capabilities. We present here an overview of the main findings about the involvement of H. pylori in the acquisition of cell invasive behavior, specifically focusing on the epithelial-to-mesenchymal transition, changes in cell polarity, and deregulation of molecules that control extracellular matrix remodeling.
基金funded by the French National Cancer Institute(INCA_N◦2018-123)and supported by Canccrole Ile-de-France(N◦2018-1-PL SHS-06-CIRC-1)supported by the International Agency for Research on Cancer(IARC)and also by the Department of Epidemiology and Biostatistics,School of Public Health,Imperial College London,which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre(BRC)+9 种基金supported by:Danish Cancer Society(Denmark)Ligue Contre le Cancer,Institut Gustave Roussy,Mutuelle Générale de l’Education Nationale,Institut National de la Santéet de la Recherche Médicale(INSERM)(France)German Cancer Aid,German Cancer Research Center(DKFZ),German Institute of Human Nutrition Potsdam-Rehbruecke(DIfE),Federal Ministry of Education and Research(BMBF)(Germany)Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy,Compagnia di SanPaolo and National Research Council(Italy)Dutch Ministry of Public Health,Welfare and Sports(VWS),Netherlands Cancer Registry(NKR),LK Research Funds,Dutch Prevention Funds,Dutch ZON(Zorg Onderzoek Nederland),World Cancer Research Fund(WCRF),Statistics Netherlands(The Netherlands)Health Research Fund(FIS)-Instituto de Salud Carlos III(ISCIII),Regional Governments ofAndalucía,Asturias,Basque Country,Murcia and Navarra,and the Catalan Institute of Oncology-ICO(Spain)Swedish Cancer Society,Swedish Research Council and County Councils of Skane and Vasterbotten(Sweden)Cancer Research UK(14136 to EPIC-NorfolkC8221/A29017 to EPIC-Oxford),Medical Research Council(1000143 to EPIC-NorfolkMR/M012190/1 to EPIC-Oxford)(United Kingdom).
文摘Owing to shared risk factors between cardiometabolic diseases(CMDs)and cancer,coupled with population aging,the lifetime risk of an individual developing cancer after a CMD is increasing.Furthermore,biological mechanisms such as insulin resistance or inflammation may not only predispose individuals withCMDto an elevated risk of certain types of cancer but also to a diagnosis of cancer at an advanced stage[1,2].
基金supported by a Wellcome Trust PhD studentship in Molecular,Genetic and Lifecourse Epidemiology(224982/Z/22/Z).
文摘Recent epidemiological studies have suggested a positive association between ultra-processed food consumption and breast cancer risk,although some studies also reported no association.Furthermore,the evidence regarding the associations between intake of food with lower degrees of processing and breast cancer risk is limited.Thus,we investigated the associations between dietary intake by degree of food processing and breast cancer risk,overall and by breast cancer subtypes in the European Prospective Investigation into Cancer and Nutrition(EPIC)study.Dietary intake of EPIC participants was assessed via questionnaires at baseline.More than 11,000 food ingredients were classified into four groups of food processing levels using the NOVA classification system:unprocessed/minimally processed(NOVA 1),culinary ingredients(NOVA 2),processed(NOVA 3)and ultra-processed(NOVA 4).Cox proportional hazards models were used to estimate hazard ratios(HRs)and 95%confidence intervals(CIs)of breast cancer per standard deviation increase in daily consumption(grams)of foods from each NOVA group.The current analysis included 14,933 breast cancer cases,diagnosed among the 318,686 EPIC female participants,(median follow-up of 14.9 years).No associations were found between breast cancer risk and the level of dietary intake from NOVA 1[HR_(per 1 SD)=0.99(95%CI 0.97-1.01)],NOVA 2[HR_(per 1 SD)=1.01(95%CI 0.98-1.03)]and NOVA 4[HR_(per 1 SD)=1.01(95%CI 0.99-1.03)]foods.However,a positive association was found between NOVA 3 and breast cancer risk[HR_(per 1 SD)=1.05(95%CI 1.03-1.07)]which became non-significant after adjustment for alcohol intake[HR_(per 1 SD)=1.01(95%CI 0.98-1.05)]or when beer and wine were excluded from this group[HR_(per 1 SD)=0.99(95%CI 0.97-1.01)].The associations did not differ by breast cancer subtype,menopausal status or body mass index.Findings from this large-scale prospective study suggest that the positive association between processed food intake and breast cancer risk was likely driven by alcoholic beverage consumption.
基金the Fondation de France(FDF,grant no.00081166,HF and RC,and FDF grant no.00089811,ALM)the Wereld Kanker Onderzoek Fonds(WKOF),as part of the World Cancer Research Fund(WCRF)International grant programme(WCRF 2015-1391,PI Dr.Mazda Jenab,International Agency for Research on Cancer)。
文摘Dear Editor,In the European region,which shares 22.8%of the global cancer burden for 10%of the global population,there were around 4.4 million new cancer cases and 1.9 million deaths from cancer in 2020[1].The reasons for the high cancer incidence rates are complex;however,diet and dietary components are among the main contributors to cancer risk[2].In modern-day living,a growing proportion of people include in their diets ultra-processed foods.Byproducts of food processing and home-prepared foods are so-called dietary advanced glycation endproducts(AGEs),which are reactive metabolites emerging during the breakdown of reducing sugar.AGEs production is preponderant in dry high-heat processes(e.g.,baking,roasting);hence foods such as cakes,crisps,crackers,cereal products,meat and meat-derived products represent a major source of dietary AGEs[3].
基金supported in part by the Cancer Research UK Cancer Grand Challenge Award(6340201/A27140)NIH grant(R01 CA248857)+1 种基金T.U.was supported by NIH grant R50 CA27412a Brigham and Women’s Hospital Faculty Career Development Award,an Investigator Initiated Grant from the American Institute for Cancer Research(AICR),a Prevent Cancer Foundation Fellowship,and the Harvey V.Fineberg Fellowship in Cancer Prevention from Harvard T.H.Chan School of Public Health.S.U.was supported by a grant from the Uehara Memorial Foundation.S.O.is an American Cancer Society Clinical Research Professor。
文摘The tumor microenvironment represents a dynamic and multifaceted milieu characterized by the complex interactions of diverse cellular and non-cellular constituents.1,2 These constituents include tumor cells,microorganisms,immune and other stromal cells,and extracellular matrices.The orchestration of these components intricately contributes to tumor evolution and shapes responses to cancer treatment(Figure 1).A better understanding of the tumor microenvironment is critical to elucidate the etiology of cancer and develop more efficient therapeutic strategies.
