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Expression of cyclin-dependent kinase 9 is positively correlated with the autophagy level in colon cancer

World Journal of Gastrointestinal Oncology 2024年第2期16卷 314-330页

作者： Lei Zheng Jia Lu Da-Lu Kong Department of Colorectal cancer Surgery National Clinical Research Center for CancerKey Laboratory of Cancer Immunology and Biotherapy of TianjinTianjin Key Laboratory of Digestive CancerKey Laboratory of Cancer Prevention and Therapy of TianjinTianjin’s Clinical Research Center for CancerTianjin Medical University Cancer Institute and HospitalTianjin 300060China Department of Infection Management National Clinical Research Center for CancerKey Laboratory of Cancer Immunology and Biotherapy of TianjinTianjin Key Laboratory of Digestive CancerKey Laboratory of Cancer Prevention and Therapy of TianjinTianjin’s Clinical Research Center for CancerTianjin Medical University Cancer Institute and HospitalTianjin 300060China

BACKGROUND Cyclin-dependent kinase 9(CDK9)expression and autophagy in colorectal cancer(CRC)tissues has not been widely ***9,a key regulator of transcription,may influence the occurrence and progression of *** expression of auto-phagy-related genes BECN1 and drug resistance factor ABCG2 may also play a role in *** normal physiological conditions,autophagy can inhibit tumorigenesis,but once a tumor forms,autophagy may promote tumor ***,understanding the relationship between autophagy and cancer,partic-ularly how autophagy promotes tumor growth after its formation,is a key motivation for this *** To investigate the relationship between CDK9 expression and autophagy in CRC,assess differences in autophagy between left and right colon cancer,and analyze the associations of autophagy-related genes with clinical features and *** We collected tumor tissues and paracarcinoma tissues from colon cancer patients with liver metastasis to observe the level of autophagy in tissues with high levels of CDK9 and low levels of *** also collected primary tissue from left and right colon cancer patients with liver metastasis to compare the autophagy levels and the expression of BECN1 and ABCG2 in the tumor and paracarcinoma *** The incidence of autophagy and the expression of BECN1 and ABCG2 were different in left and right colon cancer,and autophagy might be involved in the occurrence of chemotherapy *** analysis of the rela-tionship between the expression of autophagy-related genes CDK9,ABCG2,and BECN1 and the clinical features and prognosis of colorectal cancer showed that the high expression of CDK9 indicated a poor prognosis in colorectal *** This study laid the foundation for further research on the combination of CDK9 inhibitors and autophagy inhibitors in the treatment of patients with CRC.

关键词： Autophagy Tumorigenesis Tumor tissue Paracarcinoma tissue Expression Left/right colon cancer

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Attributable liver cancer deaths and disability-adjusted life years in China and worldwide: profiles and changing trends

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cancer Biology & Medicine 2024年第8期21卷 679-691页

作者： Mengdi Cao Changfa Xia Maomao Cao Fan Yang Xinxin Yan Siyi He Shaoli Zhang Yi Teng Qianru Li Nuopei Tan JiachenWang Wanqing Chen Office of cancer Screening National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

Objective: Liver cancer is a major health concern globally and in China. This analysis investigated deaths and disability-adjusted life years(DALYs) with respect to etiologies and risk factors for liver cancer in China and ***: Global and China-specific data were collected on liver cancer deaths, DALYs, and age-standardized rates(ASRs) from the Global Burden of Disease Study 2019 database. Liver cancer etiologies were classified into five groups and risk factors were categorized into three levels. Each proportion of liver cancer burden was calculated in different geographic regions. The joinpoint regression model were used to assess the trends from 1990±***: Liver cancer accounted for 484,577 deaths worldwide in 2019 with an ASR of 5.9 per 100,000 population. China had an elevated liver cancer death ASR in 2019 and males had an ASR 1.7 times the global rate. The global ASR for DALYs peaked at 75±79 years of age but peaked earlier in China. Hepatitis B virus was the prominent etiology globally(39.5%) and in China(62.5%), followed by hepatitis C virus and alcohol consumption. In high sociodemographic index countries, non-alcoholic steatohepatitis has gained an increasing contribution as an etiologic factor. The liver cancer burden due to various etiologies has decreased globally in both genders. However, metabolic risk factors, particularly obesity, have had a growing contribution to the liver cancer burden, especially among ***: Despite an overall decreasing trend in the liver cancer burden in China and worldwide, there has been a rising contribution from metabolic risk factors, highlighting the importance of implementing targeted prevention and control strategies that address regional and gender disparities.

关键词： Liver cancer deaths risk factors global China

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Gastric cancer secreted miR 214-3p inhibits the anti-angiogenesis effect of apatinib by suppressing ferroptosis in vascular endothelial cells

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Oncology research 2024年第3期32卷 489-502页

作者： WEIXUE WANG TONGTONG WANG YAN ZHANG TING DENG HAIYANG ZHANG YI BA Department of GI Medical Oncology Tanjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerTianjin's Clinical Research Center for CancerTianjin Key Iaboratory of Digestive CancerKey Laboratory of Cancer Prevention and TherapyTianjin300060China

Diferent from necrosis,apoptosis,autophagy and other forms of cell death,ferroptosis is a mechanism that catalyzes lipid peroxidation of polyunsaturated ftty acids under the action of iron divalent or lipoxygenase,leading to cell *** is currently used in the third line standard treatment of advanced gastric cancer,targeting the anti-angiogenesis ***,Apatinib mediated ferroptosis in vascular endothelial cells has not been reported *** exosomes can be taken up into target cells to regulate tumor development,but the mechanism related to vascular endothelial cell ferroptosis has not yet been ***,we show that exosomes secreted by gastric cancer cells carry miR-214.3p into vascular endothelial cells and directdy target zinc finger protein A20 to negatively regulate ACSL4,a key enzyme of lipid peroxidation during frroptosis thereby inhibiting ferroptosis in vascular endothelial cells and reducing the eficiency of *** conclusion,inhibition of miR-214-3p can increase the sensitivity of vascular endothelial cells to Apatinib,thereby promoting the antiangiogenic efect of Apatinib,suggesting a potential combination therapy for advanced gastric cancer.

关键词： Cellular ferroptosis Exosome Tyrosine kinase inhibitor Gastrointestinal tumors miRNA

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Intranasal boosting with RBD-HR protein vaccine elicits robust mucosal and systemic immune responses

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Genes & Diseases 2024年第4期11卷 327-339页

作者： Li Chen Wenyan Ren Hong Lei Jiayu Wang Haiying Que Dandan Wan Aqu Alu Dandan Peng Minyang Fu Weiqi Hong Yuhe Huang Xiangrong Song Guangwen Lu Xiawei Wei Laboratory of Aging research and cancer Drug Target State Key Laboratory of Biotherapy and Cancer CenterNational Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityChengduSichuan 610041China

The emergence of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)variants has decreased the efficacy of SARs-CoV-2 vaccines in containing coronavirus disease 2019(CoVID-19)over time,and booster vaccination strategies are urgently necessitated to achieve sufficient *** immunization can improvemucosal immunity,offer-ing protection against the infection and sustaining the spread of *** this study,an intranasal booster of the RBD-HR vaccine after two doses of the mRNA vaccine significantly increased the levels of specific binding antibodies in serum,nasal lavage fluid,and bronchoal-veolar lavage fluid compared with only two doses of mRNA *** intranasal boosting with the RBD-HR vaccine,the levels of serum neutralizing antibodies against prototype and variant strains of SARS-Cov-2 pseudoviruses weremarkedly higher than those in mice receiving mRNA vaccine alone,and intranasal boosting with the RBD-HR vaccine also inhibited the bind-ing of RBD to hACE2 ***,the heterologous intranasal immunization regimen promoted extensive memory T cell responses and activated CD103+dendritic cells in the respiratory mucosa,and potently enhanced the formation of T follicular helper cells and germinal center B cells in vital immune organs,including mediastinal lymph nodes,inguinal lymph nodes,and ***,these data infer that heterologous intranasal boosting with the RBD-HR vaccine elicited broad protective immunity against SARS-CoV-2 both locallyandsystemically.

关键词： Heterologous immunization Intranasal immunization mRNA vaccine SARS-CoV-2 Subunitprotein vaccine

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Effectiveness and safety of combined nimotuzumab and S-1 chemotherapy with concurrent radiotherapy for locally advanced esophageal cancer in malnourished and elderly patients:A prospective phaseⅡstudy

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Chinese Journal of cancer research 2024年第3期36卷 270-281页

作者： Guojie Feng Jiao Li Nuo Yu Ziyu Zheng Xiongtao Yang Lei Deng Tao Zhang Wenqing Wang Wenyang Liu Jianyang Wang Qinfu Feng Jima Lyu Zefen Xiao Zongmei Zhou Nan Bi Jianjun Qin Xin Wang Department of Radiation Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100021China Department of Thoracic Surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100021China

Objective:Definitive chemoradiotherapy(dCRT)is the standard treatment for unresectable locally advanced esophageal ***,this treatment is associated with substantial toxicity,and most malnourished or elderly patients are unable to complete this ***,there is a need for a more suitable radiotherapy combination regimen for this *** study was aimed to evaluate the efficacy and safety of a combination regimen comprising chemotherapy with nimotuzumab and S-1 and concurrent radiotherapy for patients with fragile locally advanced esophageal cancer with a high Nutritional Risk Screening 2002(NRS-2002)***:Eligible patients with unresectable esophageal carcinoma who had an NRS-2002 score of 2 or higher were *** were treated with S-1 and nimotuzumab with concurrent radiotherapy,followed by surgery or definitive *** primary endpoint was the locoregional control(LRC)***:A total of 55 patients who met the study criteria were *** completion of treatment,surgery was performed in 15 patients and radiotherapy was continued in 40 *** median follow-up period was 33.3[95%confidence interval(95%CI,31.4−35.1)]*** LRC rate was 77.2%(95%CI,66.6%−89.4%)at 1 year in the entire *** overall survival(OS)rate and event-free survival(EFS)rate were 57.5%and 51.5%at 3 years,*** was associated with better LRC[hazard ratio(HR)=0.16;95%CI,0.04−0.70;P=0.015],OS(HR=0.19;95%CI,0.04−0.80;P=0.024),and EFS(HR=0.25;95%CI,0.08−0.75;P=0.013).Most adverse events were of grade 1 or 2,and no severe adverse events ***:For malnourished or elderly patients with locally advanced esophageal cancer,radiotherapy combined with nimotuzumab and S-1 is effective and has a good safety profile.

关键词： Esophageal carcinoma squamous cell carcinoma nutritional risk score nimotuzumab S-1 definitive chemoradiotherapy

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Comprehensive characterization of cell disulfidptosis in human cancers:An integrated pan-cancer analysis

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Genes & Diseases 2024年第4期11卷 5-8页

作者： Guo Zhao Yale Jiang Yuning Wang Shuhang Wang Ning Li Clinical Trial center National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

Excessive accumulation of disulfide molecules,like cystine,can induce disulfide stress and high toxicity in cells,but the reduced form of nicotinamide adenine dinucleotide phosphate can reverse this process and mitiga... 详细信息

关键词： disulfide cancer characterization

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Methyltransferase-like 3(METTL3)inhibition potentiates anti-tumor immunity:a novel strategy for improving anti-PD1 therapy

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Signal Transduction and Targeted Therapy 2024年第1期9卷 10-11页

作者： Anna Brichkina Roman Suezov Magdalena Huber Institute of Systems Immunology Member of the German Center for Lung Research(DZL)Philipps University of Marburg35043 MarburgGermany

In a recent article published in cancer Discovery,Guirguis et *** that enzymatic inhibitors of the m6 A methyltransferase METTL3 induced a formation of immunostimulatory doublestranded mRNAs(dsRNAs)in cancer cells,which triggered a profound tumor-cell-intrinsic interferon response leading to an enhanced antigen presentation and thereby increased killing of tumor cells by cytotoxic CD8+*** inhibition of METTL3 synergized with anti-PD1 immunotherapy,highlighting its potential for improving cancer treatment.

关键词： PD1 immunity

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Molecular glue triggers degradation of PHGDH by enhancing the interaction between DDB1 and PHGDH

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Acta Pharmaceutica Sinica B 2024年第9期14卷 4001-4013页

作者： Ziqi Huang Kun Zhang Yurui Jiang Mengmeng Wang Mei Li Yuda Guo Ruolin Gao Ning Li Chenyang Wang Jia Chen Jiefu Wang Ning Liu Xiang Liu Shuangwei Liu Mingming Wei Cheng Yang Guang Yang The State Key Laboratory of Medicinal Chemical Biology College of Life SciencesCollege of PharmacyNankai UniversityTianjin 300071China Tianjin Medical University cancer Institute and Hospital National Clinical Research Center for CancerTianjin’s Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjin 300060China

cancer stem cells(CSCs)play a pivotal role in tumor initiation,proliferation,metastasis,drug resistance,and ***,targeting CSCs has emerged as a promising avenue for cancer ***,3-phosphoglycerate dehydrogenase(PHGDH)has been identified as being intricately associated with the regulation of numerous cancer stem ***,reports detailing the functional regulators of PHGDH that can mitigate the stemness across cancer types are *** this study,the novel“molecular glue”LXH-3-71 was identified,and it robustly induced degradation of PHGDH,thereby modulating the stemness of colorectal cancer cells(CRCs)both in vitro and in ***,LXH-3-71 was observed to form a dynamic chimera,between PHGDH and the DDB1-CRL E3 *** insights not only elucidate the anti-CSCs mechanism of the lead compound but also suggest that degradation of PHGDH may be a more viable therapeutic strategy than the development of PHGDH ***,compound LXH-3-71 was leveraged as a novel ligand for the DDB1-CRL E3 ligase,facilitating the development of new PROTAC molecules targeting EGFR and CDK4 degradation.

关键词： Molecular glue Targeted protein degradation PHGDH cancer stem cells PROTACs

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A retrospective analysis of mature T-and NK-cell lymphomas

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cancer Biology & Medicine 2024年第3期21卷 223-229页

作者： Junlei Jia Xiaohui Wang Zheng Song Shen Meng Yue Fei Jingwei Yu Xia Liu Xue Han Lanfang Li Lihua Qiu Zhengzi Qian Shiyong Zhou Wenchen Gong Bin Meng Xiubao Ren Xianhuo Wang Huilai Zhang National Key Laboratory of Druggability Evaluation and Systematic Translational Medicine and Department of LymphomaTianjin Medical University Cancer Institute&HospitalNational Clinical Research Center for CancerTianjin's Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinThe Sino-US Center for Lymphoma and Leukemia ResearchTianjin 300060China Department of Radiation Oncology Shandong Cancer Hospital and InstituteShandong First Medical University and Shandong Academy of Medical SciencesJinan 250117China Department of Pathology Department of Immunology/Biotherapy Tianjin Medical University Cancer Institute&HospitalNational Clinical Research Center for CancerTianjin's Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin 300060China

Mature T-and natural killer(NK)-cell lymphomas are heterogeneous groups of malignant lymphoid neoplasms arising from T and NK cells. The incidence of mature T-and NK-cell lymphomas is 2.1 per 100,000 people, according... 详细信息

关键词： lymphoma neoplasms killer

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Genomic medicine in clinical practice:national genomic medicine program in Japan

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cancer Biology & Medicine 2024年第1期21卷 4-9页

作者： Teruhiko Yoshida Yasushi Yatabe Ken Kato Genichiro Ishii Akinobu Hamada Hiroyuki Mano Kuniko Sunami Noboru Yamamoto Takashi Kohno Department of Genetic Medicine and Services National Cancer Center HospitalTokyo 104-0045Japan Department of Diagnostic Pathology National Cancer Center HospitalTokyo 104-0045Japan Clinical research Support Offce Clinical Research Coordinating SectionBiobank Translational Research Support SectionNational Cancer Center HospitalTokyo 104-0045Japan Department of Pathology and Clinical Laboratories National Cancer Center Hospital EastChiba 277-8577Japan Division of Molecular Pharmacology National Cancer Center Research InstituteTokyo 104-0045Japan National cancer center research Institute Tokyo 104-0045Japan Department of Laboratory Medicine National Cancer Center HospitalTokyo 104-0045Japan Department of Experimental Therapeutics National Cancer Center HospitalTokyo 104-0045Japan Division of Genome Biology National Cancer Center Research InstituteTokyo 104-0045Japan

cancer statistics in Japan cancer is the most common cause of death in Japan based on Statistics 2021~*** statistics were first gathered,infectious diseases,such as tuberculosis,and cerebrovascular disease have been the main causes of death in *** surpassed cerebrovascular disease as the main cause of death in 1981,and the number of cancer deaths has *** 38,000 people died of cancer in *** National cancer center(NCC)reported that the 5-year survival rate for patients with cancer was improving(62%for males and 66.9%for females)in a population-based cancer registry.

关键词： cancer cancer death

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