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The evolving view of thermogenic fat and its implications in cancer and metabolic diseases

Signal Transduction and Targeted Therapy 2022年第10期7卷 3727-3747页

作者： Xinpeng Yin Yuan Chen Rexiati Ruze ruiyuan xu Jianlu Song Chengcheng Wang Qiang xu Department of General Surgery State Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College HospitalChinese Academy of Medical SciencesPeking Union Medical College100023 BeijingP.R.China

The incidence of metabolism-related diseases like obesity and type 2 diabetes mellitus has reached pandemic levels worldwide and increased *** of them are listed on the table of high-risk factors for malignancy,and metabolic disorders systematically or locally contribute to cancer progression and poor prognosis of ***,adipose tissue is fundamental to the occurrence and development of these metabolic *** adipose tissue stores excessive energy,while thermogenic fat including brown and beige adipose tissue dissipates energy to generate *** addition to thermogenesis,beige and brown adipocytes also function as dynamic secretory cells and a metabolic sink of nutrients,like glucose,fatty acids,and amino ***,strategies that activate and expand thermogenic adipose tissue offer therapeutic promise to combat overweight,diabetes,and other metabolic disorders through increasing energy expenditure and enhancing glucose *** a better understanding of its origins and biological functions and the advances in imaging techniques detecting thermogenesis,the roles of thermogenic adipose tissue in tumors have been revealed *** the one hand,enhanced browning of subcutaneous fatty tissue results in weight loss and cancer-associated *** the other hand,locally activated thermogenic adipocytes in the tumor microenvironment accelerate cancer progression by offering fuel sources and is likely to develop resistance to ***,we enumerate current knowledge about the significant advances made in the origin and physiological functions of thermogenic *** addition,we discuss the multiple roles of thermogenic adipocytes in different ***,we summarize imaging technologies for identifying thermogenic adipose tissue and pharmacologic agents via modulating thermogenesis in preclinical experiments and clinical trials.

关键词： metabolism stores listed

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Lipid metabolism in pancreatic cancer:emerging roles and potential targets

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Cancer Communications 2022年第12期42卷 1234-1256页

作者： Xinpeng Yin ruiyuan xu Jianlu Song Rexiati Ruze Yuan Chen Chengcheng Wang Qiang xu Department of General Surgery Peking Union Medical College HospitalChinese Academy of Medical SciencesPeking Union Medical CollegeBeijing 100023P.R China

Pancreatic cancer is one of the most serious health issues in developed and developing countries,with a 5-year overall survival rate currently<9%.Patients typically presentwith advanced disease due to vague symptoms or lack of screening for early cancer *** resection represents the only chance for cure,but treatment options are limited for advanced diseases,such as distant metastatic or locally progressive *** adjuvant chemotherapy has improved long-term outcomes in advanced cancer patients,its response rate is ***,exploring other new treatments is *** recent years,increasing evidence has shown that lipid metabolism can support tumorigenesis and disease progression as well as treatment resistance through enhanced lipid synthesis,storage,and ***,a better understanding of lipid metabolism networks may provide novel and promising strategies for early diagnosis,prognosis estimation,and targeted therapy for pancreatic cancer *** this review,we first enumerate and discuss current knowledge about the advances made in understanding the regulation of lipid metabolism in pancreatic *** addition,we summarize preclinical studies and clinical trials with drugs targeting lipid metabolic systems in pancreatic ***,we highlight the challenges and opportunities for targeting lipid metabolism pathways through precision therapies in pancreatic cancer.

关键词： clinical trials lipid metabolism pancreatic cancer targeting therapy

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Early screening and diagnosis strategies of pancreatic cancer:a comprehensive review

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Cancer Communications 2021年第12期41卷 1257-1274页

作者： Jinshou Yang ruiyuan xu Chengcheng Wang Jiangdong Qiu Bo Ren Lei You Department of General Surgery Peking Union Medical College HospitalChinese Academy of Medical SciencesPeking Union Medical CollegeBeijingP.R.China

Pancreatic cancer is a highly malignant digestive system tumor with a poor *** pancreatic cancer patients are diagnosed at an advanced stage or even metastasis due to its highly aggressive characteristics and lack of typical early ***,an early diagnosis of pancreatic cancer is crucial for improving its ***,screening is often applied in high-risk individuals to achieve the early diagnosis of pancreatic *** understanding the risk factors of pancreatic cancer and pathogenesis could help us identify the high-risk population and achieve early diagnosis and timely treatment of pancreatic ***,accumulating studies have been undertaken to improve the detection rate of different imaging methods and the diagnostic accuracy of endoscopic ultrasound-guided fine-needle aspiration(EUS-FNA)which is the golden standard for pancreatic cancer *** addition,there are currently no biomarkers with sufficient sensitivity and specificity for the diagnosis ofpancreatic cancer to be applied in the clinic. As the only serum biomarkerapproved by the United States Food and Drug Administration, carbohydrateantigen 19-9 (CA19-9) is not recommended to be used in the early screeningof pancreatic cancer because of its limited specificity. Recently, increasingnumbers of studies focused on the discovering of novel serum biomarkersand exploring their combination with CA19-9 in the detection of pancreaticcancer. Besides, the application of liquid biopsy involving circulating tumor cells(CTCs), circulating tumor DNA (ctDNA), microRNAs (miRNAs), and exosomesin blood and biomarkers in urine, and saliva in pancreatic cancer diagnosis aredrawing more and more attention. Furthermore, many innovative technologiessuch as artificial intelligence, computer-aided diagnosis system, metabolomicstechnology, ion mobility spectrometry (IMS) associated technologies, and novelnanomaterials have been tested for the early diagnosis of pancreatic cancer andhav

关键词： biomarker diagnosis early screening imaging liquid biopsy pancreatic cancer pathological examination risk factor serological examination

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Mechanisms of obesity-and diabetes mellitus-related pancreatic carcinogenesis:a comprehensive and systematic

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Signal Transduction and Targeted Therapy 2023年第4期8卷 1743-1783页

作者： Rexiati Ruze Jianlu Song Xinpeng Yin Yuan Chen ruiyuan xu Chengcheng Wang Yupei Zhao Department of General Surgery Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical College100730 BeijingChina Key Laboratory of Research in Pancreatic Tumors Chinese Academy of Medical Sciences100023 BeijingChina Chinese Academy of Medical Sciences and Peking Union Medical College No.9 Dongdan SantiaoBeijingChina

Research on obesity-and diabetes mellitus(DM)-related carcinogenesis has expanded exponentially since these two diseases were recognized as important risk factors for *** growing interest in this area is prominently actuated by the increasing obesity and DM prevalence,which is partially responsible for the slight but constant increase in pancreatic cancer(PC)*** is a highly lethal malignancy characterized by its insidious symptoms,delayed diagnosis,and devastating *** intricate process of obesity and DM promoting pancreatic carcinogenesis involves their local impact on the pancreas and concurrent wholebody systemic changes that are suitable for cancer *** main mechanisms involved in this process include the excessive accumulation of various nutrients and metabolites promoting carcinogenesis directly while also aggravating mutagenic and carcinogenic metabolic disorders by affecting multiple *** alterations in gastrointestinal and sex hormone levels and microbiome dysfunction further compromise immunometabolic regulation and contribute to the establishment of an immunosuppressive tumor microenvironment(TME)for carcinogenesis,which can be exacerbated by several crucial pathophysiological processes and TME components,such as autophagy,endoplasmic reticulum stress,oxidative stress,epithelialmesenchymal transition,and exosome *** review provides a comprehensive and critical analysis of the immunometabolic mechanisms of obesity-and DM-related pancreatic carcinogenesis and dissects how metabolic disorders impair anticancer immunity and influence pathophysiological processes to favor cancer initiation.

关键词： carcinogenesis obesity immunity

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The role of histone methylation in the development of digestive cancers:a potential direction for cancer management

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Signal Transduction and Targeted Therapy 2020年第1期5卷 1226-1238页

作者： Yuan Chen Bo Ren Jinshou Yang Huanyu Wang Gang Yang ruiyuan xu Lei You Yupei Zhao Department of General Surgery Peking Union Medical College HospitalChinese Academy of Medical SciencesPeking Union Medical College100023 BeijingPR China

Digestive cancers are the leading cause of cancer-related death worldwide and have high risks of morbidity and *** methylation,which is mediated mainly by lysine methyltransferases,lysine demethylases,and protein arginine methyltransferases,has emerged as an essential mechanism regulating pathological processes in digestive *** certain conditions,aberrant expression of these modifiers leads to abnormal histone methylation or demethylation in the corresponding cancer-related genes,which contributes to different processes and phenotypes,such as carcinogenesis,proliferation,metabolic reprogramming,epithelial–mesenchymal transition,invasion,and migration,during digestive cancer *** this review,we focus on the association between histone methylation regulation and the development of digestive cancers,including gastric cancer,liver cancer,pancreatic cancer,and colorectal cancer,as well as on its clinical application prospects,aiming to provide a new perspective on the management of digestive cancers.

关键词： invasion mortality digestive

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