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Recent advances in cancer-associated fibroblast:Biomarkers,signaling pathways,and therapeutic opportunities

Chinese Medical Journal 2024年第6期137卷 638-650页

作者： Donger Zhou Lei Zheng Department of Hepatobiliary-Pancreatic Surgery The Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310009China Sidney Kimmel Comprehensive cancer center The Skip Viragh Pancreatic Cancer Center for Clinical Research and Careand The Bloomberg-Kimmel Institute for Immunotherapy at Johns Hopkins University School of MedicineBaltimoreMD 21287USA

Anti-cancer therapies usually focus on tumor cells,but non-tumor stromal components in the tumor microenvironment also play vital roles in tumor initiation and progression,which may be the prognostic factors and potential therapeutic targets.cancer-associated fibroblasts(CAFs)are the essential component in the tumor environment,exhibiting high heterogeneity in their cell origin and phenotype with diverse functions that influence tumor angiogenesis,immune systems,and metabolism.Single-cell RNA sequencing and genetically engineered mouse models have increased our understanding of CAF diversity,and many subtypes have been defined.However,the precise functions of these subtypes need to be studied and validated.Studies of signaling pathways and epigenetic changes in CAFs facilitate understanding of the phenotypes of CAFs and the crosstalk between tumor cells and CAFs to provide potential therapeutic targets.Some clinical trials,including phase III trials targeting CAFs,have been performed recently.However,few of these trials have generated promising results,which indicates that the complexity of CAFs in the tumor microenvironment remains largely unknown,and in-depth investigations of CAFs should be performed.This review summarizes the research on CAFs,focusing on the heterogeneity of their phenotypes and functions,specific signaling pathways,and the therapeutic strategies involving CAFs.Additionally,we briefly discuss the current technologies commonly used in CAF studies and describe the challenges and future perspectives of CAF research.

关键词： cancer-associated fibroblasts Tumor microenvironment Anti-cancer therapy Targeted therapy

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Lipid metabolism analysis in esophageal cancer and associated drug discovery

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Journal of Pharmaceutical Analysis 2024年第1期14卷 1-15页

作者： Ruidi Jiao Wei Jiang Kunpeng Xu Qian Luo Luhua Wang Chao Zhao Bionic Sensing and Intelligence center Institute of Biomedical and Health EngineeringShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong518000China Department of Radiation Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital&Shenzhen HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeShenzhenGuangdong518116China School of Medicine Southern University of Science and TechnologyShenzhenGuangdong518000China University of Chinese Academy of Sciences Beijing100049China Shenzhen Key Laboratory of Precision Diagnosis and Treatment of Depression Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong518000China

Esophageal cancer is an upper gastrointestinal malignancy with a bleak prognosis.It is still being explored in depth due to its complex molecular mechanisms of occurrence and development.Lipids play a crucial role in cells by participating in energy supply,biofilm formation,and signal transduction processes,and lipid metabolic reprogramming also constitutes a significant characteristic of malignant tumors.More and more studies have found esophageal cancer has obvious lipid metabolism abnormalities throughout its beginning,progress,and treatment resistance.The inhibition of tumor growth and the enhancement of antitumor therapy efficacy can be achieved through the regulation of lipid metabolism.Therefore,we reviewed and analyzed the research results and latest findings for lipid metabolism and associated analysis techniques in esophageal cancer,and comprehensively proved the value of lipid metabolic reprogramming in the evolution and treatment resistance of esophageal cancer,as well as its significance in exploring potential therapeutic targets and biomarkers.

关键词： Lipid metabolism Esophageal cancer Progression Treatment resistance New therapeutic targets

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Current status of early gastric cancer screening research

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cancer Biology & Medicine 2024年第3期21卷 218-222页

作者： Can Hu Li Yuan Xiangdong Cheng Department of Gastric surgery Zhejiang Cancer HospitalHangzhou Institute of Medicine(HIM)Chinese Academy of SciencesHangzhouZhejiang 310022China Key Laboratory of Prevention Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang ProvinceHangzhou 310022China Zhejiang Provincial research center for Upper Gastrointestinal Tract cancer Zhejiang Cancer HospitalHangzhou 310022China

Gastric cancer is a predominant threat to the health and well-being of China's residents. Data from the World Health Organization(WHO) in 2020 revealed that gastric cancer in China notably accounted for 44.0% of new c... 详细信息

关键词： cancer Gastric gastric

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Molecular features of gastroenteropancreatic neuroendocrine carcinoma: A comparative analysis with lung neuroendocrine carcinoma and digestive adenocarcinomas

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Chinese Journal of cancer research 2024年第1期36卷 90-102页

作者： Jianwei Zhang Hanxiao Chen Junli Zhang Sha Wang Yanfang Guan Wenguang Gu Jie Li Xiaotian Zhang Jian Li Xicheng Wang Zhihao Lu Jun Zhou Zhi Peng Yu Sun Yang Shao Lin Shen Minglei Zhuo Ming Lu Key Laboratory of Carcinogenesis and Translational research(Ministry of Education/Beijing) Department of Gastrointestinal OncologyPeking University Cancer Hospital&InstituteBeijing 100142China Department of Radiation Therapy National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital&Shenzhen HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeShenzhen 518172China Key Laboratory of Carcinogenesis and Translational research(Ministry of Education/Beijing) Department I of Thoracic OncologyPeking University Cancer Hospital&InstituteBeijing 100142China Medical Department Nanjing Geneseeq Technology Inc.Nanjing 210061China Geneplus-Beijing Beijing 102200China State Key Laboratory of Holistic Integrative Management of Gastrointestinal cancers Beijing Key Laboratory of Carcinogenesis and Translational ResearchDepartment of Gastrointestinal OncologyPeking University Cancer Hospital&InstituteBeijing 100142China Key Laboratory of Carcinogenesis and Translational research(Ministry of Education/Beijing) Department of PathologyPeking University Cancer Hospital&InstituteBeijing 100142China

Objective: There is an ongoing debate about whether the management of gastroenteropancreatic(GEP)neuroendocrine carcinoma(NEC) should follow the guidelines of small-cell lung cancer(SCLC). We aim to identify the genetic differences of GEPNEC and its counterpart.Methods: We recruited GEPNEC patients as the main cohort, with lung NEC and digestive adenocarcinomas as comparative cohorts. All patients undergone next-generation sequencing(NGS). Different gene alterations were compared and analyzed between GEPNEC and lung NEC(LNEC), GEPNEC and adenocarcinoma to yield the remarkable genes.Results: We recruited 257 patients, including 99 GEPNEC, 57 LNEC, and 101 digestive adenocarcinomas.Among the mutations, KRAS, RB1, TERT, IL7R, and CTNNB1 were found to have different gene alterations between GEPNEC and LNEC samples. Specific genes for each site were revealed: gastric NEC(TERT amplification),colorectal NEC(KRAS mutation), and bile tract NEC(ARID1A mutation). The gene disparities between small-cell NEC(SCNEC) and large-cell NEC(LCNEC) were KEAP1 and CDH1. Digestive adenocarcinoma was also compared with GEPNEC and suggested RB1, APC, and KRAS as significant genes. The TP53/RB1 mutation pattern was associated with first-line effectiveness. Putative targetable genes and biomarkers in GEPNEC were identified in22.2% of the patients, and they had longer progression-free survival(PFS) upon targetable treatment [12.5 months vs. 3.0 months, HR=0.40(0.21-0.75), P=0.006].Conclusions: This work demonstrated striking gene distinctions in GEPNEC compared with LNEC and adenocarcinoma and their clinical utility.

关键词： Neuroendocrine carcinoma gastroenteropancreatic lung genetic alterations molecular markers

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Challenges and opportunities in rare cancer research in China

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Science China(Life Sciences) 2024年第2期67卷 274-285页

作者： Jianxin Xue Qunyan Lyu Division of Thoracic Tumor Multimodality Treatment Cancer CenterWest China HospitalSichuan UniversityChengdu 610041China national Natural Science Foundation of China Beijing 100085China

cancer is one of the major public health challenges in China.Rare cancers collectively account for a considerable proportion of all malignancies.The lack of awareness of rare cancers among healthcare professionals and the general public,the typically complex and delayed diagnosis,and limited access to clinical trials are key challenges.Recent years have witnessed an increase in funding for research related to rare cancers in China.In this review,we provide a comprehensive overview of rare cancers and summarize the status of research on rare cancers in China and overseas,including the trends of funding and publications.We also highlight the challenges and perspectives regarding rare cancers in China.

关键词： rare cancers basic research clinical research preclinical model funding scheme

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First-line immunotherapy for advanced non-small cell lung cancer:current progress and future prospects

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cancer Biology & Medicine 2024年第2期21卷 117-124页

作者： Jingyi Wang Lin Wu The Second Department of Thoracic Oncology Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of MedicineCentral South UniversityChangsha 410013China Xiangya Lung cancer center Xiangya HospitalCentral South UniversityChangsha 410008China

Global cancer Statistics 2022 reported the prevalence and high mortality rate of lung cancer.Notably,non-small cell lung cancer(NSCLC)accounts for the majority of the histologic types1.Precision therapy for lung cancer has progressed rapidly and immune checkpoint inhibitors(ICIs)have become a leading research topic.Indeed,ICI therapy has been shown to improve the prognosis of lung cancer patients.

关键词： lung cancer mortality

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Targeting LTA4H facilitates the reshaping of the immune microenvironment mediated by CCL5 and sensitizes ovarian cancer to Cisplatin

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Science China(Life Sciences) 2024年第6期67卷 1226-1241页

作者： Zhengyang Guo Jiaqi Huang Xiao Huo Chen Huang Xiaotong Yu Yan Sun Yanfang Li Tianhui He Hongyan Guo Jianling Yang Lixiang Xue cancer center of Peking University Third hospital Beijing 100191China center of Basic Medical research Institute of Medical Innovation and ResearchPeking University Third HospitalBeijing 100191China Peking University Third hospital cancer center Department of Radiation OncologyPeking University Third HospitalBeijing 100191China Department of Obstetrics and Gynecology Peking University Third HospitalBeijing 100191China

Ovarian cancer is the most lethal and aggressive gynecological cancer with a high recurrence rate and is often diagnosed late.In ovarian cancer,multiple metabolic enzymes of lipid metabolism are abnormally expressed,resulting in metabolism disorder.As a characteristic pathway in polyunsaturated fatty acid(PUFA)metabolism,arachidonic acid(AA)metabolism is disturbed in ovarian cancer.Therefore,we established a 10-gene signature model to evaluate the prognostic risk of PUFA-related genes.This 10-gene signature has strong robustness and can play a stable predictive role in datasets of various platforms(TCGA,ICGC,and GSE17260).The high association between the risk subgroups and clinical characteristics indicated a good performance of the model.Our data further indicated that the high expression of LTA4H was positively correlated with poor prognosis in ovarian cancer.Deficiency of LTA4H enhanced sensitivity to Cisplatin and modified the characteristics of immune cell infiltration in ovarian cancer.Additionally,our results indicate that CCL5 was involved in the aberrant metabolism of the AA/LTA4H axis,which contributes to the reduction of tumor-infiltrating CD8+T cells and immune escape in ovarian cancer.These findings provide new insights into the prognosis and potential target of LTA4H/CCL5 in treating ovarian cancer.

关键词： ovarian cancer polyunsaturated fatty acids prognostic risk model LTA4H tumor immunity CCL5

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Cognitive impairment in cerebral small vessel disease induced by hypertension

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Neural Regeneration research 2024年第7期19卷 1454-1462页

作者： Weipeng Wei Denglei Ma Lin Li Lan Zhang Department of Pharmacy Xuanwu Hospital of Capital Medical UniversityBeijingChina Beijing Geriatric Medical research center Beijing Engineering Research Center for Nervous System DrugsNational Center for Neurological DisordersNational Clinical Research Center for Geriatric DiseasesBeijingChina

Hypertension is a primary risk factor for the progression of cognitive impairment caused by cerebral small vessel disease,the most common cerebrovascular disease.Howeve r,the causal relationship between hypertension and cerebral small vessel disease remains unclear.Hypertension has substantial negative impacts on brain health and is recognized as a risk factor for cerebrovascular disease.Chronic hypertension and lifestyle factors are associated with risks for stro ke and dementia,and cerebral small vessel disease can cause dementia and stroke.Hypertension is the main driver of cerebral small vessel disease,which changes the structure and function of cerebral vessels via various mechanisms and leads to lacunar infarction,leukoaraiosis,white matter lesions,and intracerebral hemorrhage,ultimately res ulting in cognitive decline and demonstrating that the brain is the to rget organ of hypertension.This review updates our understanding of the pathogenesis of hypertensioninduced cerebral small vessel disease and the res ulting changes in brain structure and function and declines in cognitive ability.We also discuss drugs to treat cerebral small vessel disease and cognitive impairment.

关键词： blood-brain barrier cerebral small vessel disease cognitive impairment dementia endothelial dysfunction enlarged perivascular space hypertension lacunar infarction neuroinflammation treatment white matter high signal intensity

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Fe-Zn alloy, a new biodegradable material capable of reducing RoS and inhibiting oxidative stress

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Regenerative Biomaterials 2024年第2期3卷 114-122页

作者： Shuaikang Yang Weiqiang Wang Yanan Xu Yonghui Yuan Shengzhi Hao School of Materials Science and Engineering Dalian University of TechnologyDalian 116024PR China clinical research center for Malignant Tumor of Liaoning Province Cancer Hospital of Dalian University of TechnologyShenyang 110042PR China

Fe-based biodegradable materials have attracted significant attention due to their exceptional mechanical properties and favorable biocompatibility.Currently,research on Fe-based materials mainly focuses on regulating the degradation rate.However,excessive release of Fe ions during material degrada-tion will induce the generation of reactive oxygen species(ROS),leading to oxidative stress and ferroptosis.Therefore,the con-trol of RoS release and the improvement of biocompatibility for Fe-based materials are very important.In this study,new Fe-Zn alloys were prepared by electrodeposition with the intention of using Zn as an antioxidant to reduce oxidative damage during alloy degradation.Initially,the impact of three potential degra-dation ions(Fe^(2+),Fe^(3+),Zn^(2+))from the Fe-Zn alloy on human endothelial cell(EC)activity and migration ability was investigated.Subsequently,cell adhesion,cell activity,ROs production and DNA damage were assessed at various locations surrounding the alloy.Finally,the influence of different concentrations of Zn^(2+) in the medium on cell viability and ROS production was evaluated.High levels of ROS exhibited evident toxic effects on ECs and promoted DNA damage.As an antioxidant,Zn?+effectively reduced ROS production around Fe and improved the cell viability on its surface at a concentration of 0.04 mmol/l.These findings demonstrate that Fe-Zn alloy can attenuate the ROS generated from Fe degradation therebyenhancingcytocompatibility.

关键词： biodegradable iron Fe-Zn alloys reactive oxygen species oxidative stress cytocompatibility

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Modifiable risk factors for esophageal cancer in endoscopic screening population:A modeling study

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Chinese Medical Journal 2024年第3期137卷 350-352页

作者： Qian Zhang Fan Wang Hao Feng Jie Xing Shengtao Zhu Hao Zhang Yang Li Wenqiang Wei Shutian Zhang Department of Gastroenterology Beijing Friendship HospitalCapital Medical UniversityNational Clinical Research Center for Digestive DiseaseBeijing Digestive Disease CenterBeijing Key Laboratory for Precancerous Lesion of Digestive DiseaseBeijing 100050China center for Applied Statistics and School of Statistics Renmin University of ChinaBeijing 100872China Statistical Consulting center Renmin University of ChinaBeijing 100872China national cancer center National Clinical Research Center for CancerCancer InstituteChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Peking Union Medical College hospital Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China Department of Gastroenterology Jizhong Energy Fengfeng Group HospitalHandanHebei 056000China RSS and China-Re Life Joint Lab on Public Health and Risk Management Renmin University of ChinaBeijing 100872China

To the Editor:Esophageal cancer,one of the most common cancer types in China,with an estimated 346,633 new cases and 323,600 deaths in 2022,is becoming an increasingly serious clinical and public health problem.^([1])The successful promotion of the self-management strategy has indicated that lifestyle modifications can be valuable in the primary prevention of cancer development.Adopting a healthy lifestyle has become a novel strategy for primary prevention and risk reduction in high-risk areas.Previous epidemiological studies have identified several lifestyle-related risk factors for esophageal cancer,including smoking and diet.^([2])Each factor can typically explain a modest proportion of cancer risk.However,when combined,these known risk factors may substantially affect the risk of esophageal cancer.Nevertheless,some risk factors for esophageal cancer are non-modifiable,including age,low socioeconomic status,and family history.Whether and how these non-modifiable risk factors affect primary cancer prevention by intervening with modifiable risk factors remain unclear.

关键词： esophageal prevention promotion

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