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Progress in clinical diagnosis and treatment of colorectal cancer with rare genetic variants

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Cancer Biology & Medicine 2024年第6期21卷 473-483页

作者： Shuyi Chen Jing Gu Kaichun Wu Xiaodi Zhao Yuanyuan Lu State Key Laboratory of Holistic Integrative Management of gastrointestinal Cancers and National Clinical research center for Digestive diseases Xijing Hospital of Digestive DiseasesFourth Military Medical UniversityXi’an 710032China School of Basic Medical Sciences Fourth Military Medical UniversityXi’an 710032China

Targeted therapy is crucial for advanced colorectal cancer(CRC) positive for genetic drivers. With advances in deep sequencing technology and new targeted drugs, existing standard molecular pathological detection systems and therapeutic strategies can no longer meet the requirements for careful management of patients with advanced CRC. Thus, rare genetic variations require diagnosis and targeted therapy in clinical practice. Rare gene mutations, amplifications, and rearrangements are usually associated with poor prognosis and poor response to conventional therapy. This review summarizes the clinical diagnosis and treatment of rare genetic variations, in genes including erb-b2 receptor tyrosine kinase 2(ERBB2), B-Raf proto-oncogene, serine/threonine kinase(BRAF), ALK receptor tyrosine kinase/ROS proto-oncogene 1, receptor tyrosine kinase(ALK/ROS1), neurotrophic receptor tyrosine kinases(NTRKs), ret proto-oncogene(RET), fibroblast growth factor receptor 2(FGFR2), and epidermal growth factor receptor(EGFR), to enhance understanding and identify more accurate personalized treatments for patients with rare genetic variations.

关键词： Genetic variation gene mutation gene amplification gene rearrangement targeted therapy

Emerging trends in early-onset gastric cancer

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中华医学杂志(英文版) 2024年第18期137卷 2024 Aug 15页

作者： Wang Xinlin Gao Xianchun Yu Jun Zhang Xiaotian Nie Yongzhan State Key Laboratory of Holistic Integrative Management of gastrointestinal Cancers Xi’an Shaanxi China National Clinical research center for Digestive diseases Xijing Hospital of Digestive Diseases Fourth Military Medical University Xi’an Shaanxi China Beijing Key Laboratory of Carcinogenesis and Translational research Department of Gastrointestinal Oncology Peking University Cancer Hospital &amp Institute Beijing China

The incidence of early-onset gastric cancer (EOGC) is consistently increasing, and its etiology is notably complex. This increase may be attributed to distinctive factors that differ from those associated with late-onset gastric cancer (LOGC), including genetic predispositions, dietary factors, gastric microbiota dysbiosis, and screening of high-risk cases. These factors collectively contribute to the onset of cancer. EOGC significantly differs from LOGC in terms of clinicopathological and molecular characteristics. Moreover, multiple differences in prognosis and clinical management also exist. This study aimed to systematically review the latest research advancements in the epidemiological characteristics, etiological factors, clinicopathological and molecular features, prognosis, and treatment modalities of EOGC.

关键词： Early-onset gastric cancer Epidemiology Etiology Clinicopathological features Molecular signaling Prognosis Clinical management

Radiation injury and gut microbiota-based treatment

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Protein & Cell 2024年第2期15卷 83-97页

作者： Weihong Wang Bota Cui Yongzhan Nie Lijuan Sun Faming Zhang Department of Microbiota Medicine and Medical center for Digestive diseases The Second Affiliated Hospital of Nanjing Medical UniversityNanjing210011China Department of Microbiotherapy Sir Run Run HospitalNanjing Medical UniversityNanjing 211166China State Key Laboratory of Holistic Integrative Management of gastrointestinal Cancers and National Clinical research center for Digestive diseases Xijing Hospital of Digestive DiseasesFourth Military Medical UniversityXi'an 710032China National Clinical research center for Digestive diseases Xi'an 710032China Key Laboratory of Resource Biology and Biotechnology in Western China Ministry of EducationSchool of MedicineNorthwest UniversityXi'an 710069China

The exposure to either medical sources or accidental radiation can cause varying degrees of radiation injury(RI).RI is a common disease involving multiple human body parts and organs,yet effective treatments are currently *** evidence suggests gut microbiota are closely associated with the development and prevention of various *** article summarizes 10 common types of RI and their possible *** also highlights the changes and potential microbiota-based treatments for RI,including probiotics,metabolites,and microbiota ***,a 5P-Framework is proposed to provide a comprehensive strategy for managing RI.

关键词： microbiome ionizing radiation radiation-induced injury short-chain fatty acids fecal microbiota transplant washed microbiota transplantation war nuclear microbiota medicine

The switch triggering the invasion process:Lipid metabolism in the metastasis of hepatocellular carcinoma

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Chinese Medical Journal 2024年第11期137卷 1271-1284页

作者： Jiaqian Zhang Zhicheng Zhang Zhangfan Wu Yufei Wang Zerui Zhang Limin Xia Department of Gastroenterology Institute of Liver and Gastrointestinal DiseasesHubei Key Laboratory of Hepato-Pancreato-Biliary DiseasesTongji Hospital of Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430030China State Key Laboratory of Holistic Integrative Management of gastrointestinal Cancers and National Clinical research center for Digestive diseases Xijing Hospital of Digestive DiseasesFourth Military Medical UniversityXi’anShaanxi 710032China

In humans,the liver is a central metabolic organ with a complex and unique histological *** carcinoma(HCC),which is a highly aggressive disease with a poor prognosis,accounts for most cases of primary liver *** an emerging hallmark of cancers,metabolic reprogramming acts as a runaway mechanism that disrupts homeostasis of the affected organs,including the ***,rewiring of the liver metabolic microenvironment,including lipid metabolism,is driven by HCC cells,propelling the phenotypes of HCC cells,including dissemination,invasion,and even metastasis in *** resulting formation of this vicious loop facilitates various malignant behaviors of HCC ***,few articles have comprehensively summarized lipid reprogramming in HCC ***,we have reviewed the general situation of the liver microenvironment and the physiological lipid metabolism in the liver,and highlighted the effects of different aspects of lipid metabolism on HCC metastasis to explore the underlying *** addition,we have recapitulated promising therapeutic strategies targeting lipid metabolism and the effects of lipid metabolic reprogramming on the efficacy of HCC systematical therapy,aiming to offer new perspectives for targeted therapy.

关键词： Hepatocellular carcinoma Invasion Metastasis Lipid metabolism Tumor microenvironment

Exploring the potential of extrachromosomal DNA as a novel oncogenic driver

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Science China Life Sciences 2024年

作者： Huanbo Zhu Longtao Huangfu Junbing Chen Jiafu Ji Xiaofang Xing Key Laboratory of Carcinogenesis and Translational research (Ministry of Education/Beijing) Division of Gastrointestinal Cancer Translational Research Laboratory Peking University Cancer Hospital &Institute Department of gastrointestinal Cancer center Peking University Cancer Hospital & Institute Department of liver Surgery & Transplantation Liver Cancer Institute Zhongshan Hospital Fudan University Key Laboratory of Carcinogenesis and Cancer Invasion Ministry of Education State Key Laboratory of Holistic Integrative Management of gastrointestinal Cancers Beijing Key Laboratory of Carcinogenesis and Translational Research Division of Gastrointestinal Cancer Translational Research Laboratory Peking University Cancer Hospital & Institute

Extrachromosomal DNA(ecDNA) is a form of circular DNA mostly found in tumor cells. Unlike the typical chromosomal DNA, ecDNA is circular, self-replicating, and carries complete or partial gene fragments. Although ecDNA occurrence remains a rare event in cancer, recent studies have shown that oncogene amplification on ecDNA is widespread throughout many types of cancer, implying that ecDNA plays a central role in accelerating tumor evolution. ecDNA has also been associated with increased tumor mutation burden, chromosomal instability, and even tumor microenvironment remodeling. ecDNA may be crucial in influencing tumor heterogeneity, drug sensitivity,oncogenic senescence, and tumor immunogenicity, leading to a worsening prognosis for tumor patients. In this way, several clinical trials have been conducted to investigate the importance of ecDNA in clinical treatment. In this review, we summarize the biogenesis, characteristics, and current research methods of ecDNA, discuss the vital role of ecDNA-caused tumor heterogeneity in cancers, and highlight the potential role of ecDNA in cancer therapy.

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Astragaloside IV Alleviates Acute liver Failure Induced by D-GalN/LPS by Upregulating Autophagy and Reducing Inflammation

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Infectious Microbes & diseases 2024年第1期6卷 20-28页

作者： Meng Hong Wenwen Lian Ying Yang Zhi Chen State Key Laboratory for Diagnosis and Treatment of Infectious diseases National Clinical Research Center for Infectious DiseasesNational Medical Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhouChina

Acute liver failure(ALF)is a life-threatening condition that manifests in an extremely serious manner and progresses *** following study investigated the protective effect of astragaloside IV(AS-IV),a traditional Chinese drug,on ALF,and its underlying mechanisms,focusing on autophagy and inflammation *** were randomly divided into a saline group,a D-galactosamine and lipopolysac-charide(D-GalN/LPS)group and an AS-IV *** analysis,immunohistochemistry,cytometric bead array,high-throughput quantitative PCR,flow cytometry and Western analysis were used to assess inflammation and liver damage 5 hours after D-GalN/LPS *** IV treatment reduced mortality by alleviating D-GalN/LPS–induced hepatic damage and decreasing inflammation(decreasing Ly6c+monocyte levels,reducing inflammatory cytokines and increasing anti-inflammatory factors)as well as upregulating ***,PCR array was used to detect expression of autophagy-related genes,which demonstrated a Log2 fold change in gene expression between the AS-IV and D-GalN/LPS groups ranging from 1.19 to-3.53,with Tnfsf10 showing the largest alteration be-tween the two *** data suggest that AS-IV may alleviate ALF by upregulating autophagy and reducing inflammation,and it may therefore be an interesting drug for alleviating ALF.

关键词： astragaloside IV acute liver failure inflammation autophagy

Mitochondrial dysfunction: A promising therapeutic target for liver diseases

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Genes & diseases 2024年第3期11卷 324-337页

作者： Ping Chen Lichao Yao Mengqin Yuan Zheng Wang Qiuling Zhang Yingan Jiang Lanjuan Li Department of Infectious diseases Renmin Hospital of Wuhan UniversityWuhanHubei 430060China State Key Laboratory for Diagnosis and Treatment of Infectious diseases National Clinical Research Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhouZhejiang 310003China

The liver is an important metabolic and detoxification organ and hence demands a large amount of energy,which is mainly produced by the *** tissues of pa-tients with alcohol-related or non-alcohol-related liver diseases contain ultrastructural mito-chondrial lesions,mitochondrial DNA damage,disturbed mitochondrial dynamics,and compromised ATP *** of mitochondrial reactive oxygen species in-duces oxidative damage to mitochondrial proteins and mitochondrial DNA,decreases mito-chondrial membrane potential,triggers hepatocyte inflammation,and promotes programmed cell death,all of which impair liver *** DNA may be a poten-tial novel non-invasive biomarker of the risk of progression to liver cirrhosis and hepatocellular carcinoma in patients infected with the hepatitis B *** herein present a review of the mechanisms of mitochondrial dysfunction in the development of acute liver injury and chronic liver diseases,such as hepatocellular carcinoma,viral hepatitis,drug-induced liver injury,alcoholic liver disease,and non-alcoholic fatty liver *** review also discusses mito-chondrion-centric therapies for treating liver diseases.

关键词： Chronic diseases liverdamage Mesenchymalstem cell Mitochondrial dysfunction Oxidativestress

Advancements in Barrett's esophagus detection:The role of artificial intelligence and its implications

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World Journal of Gastroenterology 2024年第11期30卷 1494-1496页

作者： Sara Massironi Division of Gastroenterology and center for Autoimmune liver diseases Department of Medicine and SurgeryFondazione IRCCS San Gerardo dei TintoriUniversity of Milano-BicoccaMonza 20900Italy

Artificial intelligence(AI)is making significant strides in revolutionizing the detection of Barrett's esophagus(BE),a precursor to esophageal *** the research article by Tsai et al,researchers utilized endoscopic images to train an AI model,challenging the traditional distinction between endoscopic and histological *** approach yielded remarkable results,with the AI system achieving an accuracy of 94.37%,sensitivity of 94.29%,and specificity of 94.44%.The study's extensive dataset enhances the AI model's practicality,offering valuable support to endoscopists by minimizing unnecessary ***,questions about the applicability to different endoscopic systems *** study underscores the potential of AI in BE detection while highlighting the need for further research to assess its adaptability to diverse clinical settings.

关键词： Barrett's esophagus Artificial intelligence Endoscopic images Artificial intelligence model Early cancer detection Endoscopy

Neoadjuvant chemotherapy with capecitabine combined with oxaliplatin for mid-low locally advanced rectal cancer with negative mesorectal fascia:Long-term outcomes of a prospective trial(PKUCH-R03 trial)

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Chinese Journal of Cancer research 2024年第4期36卷 410-420页

作者： Nan Chen Minghe Zhao Yunfeng Yao Lin Wang Yifan Peng Tingting Sun Tiancheng Zhan Jun Zhao Aiwen Wu Key Laboratory of Carcinogenesis and Translational research(Ministry of Education/Beijing) Gastrointestinal Cancer CenterUnit IIIPeking University Cancer Hospital&InstituteBeijing 100142China State Key Laboratory of Holistic Integrative Management of gastrointestinal Cancers Beijing Key Laboratory of Carcinogenesis and Translational ResearchGastrointestinal Cancer CenterUnit IIIPeking University Cancer Hospital&InstituteBeijing 100142China

Objective:To evaluate the safety and efficacy of neoadjuvant chemotherapy(NCT)in mid-low locally advanced rectal cancer with negative mesorectal fascia(MRF).Methods:This prospective,single-arm phaseⅡtrial was designed and conducted at Peking University Cancer *** patients who provided consent received 3 months of NCT(capecitabine and oxaliplatin,CapOX)followed by total mesorectal excision(TME).The primary endpoint was the rate of pathological complete response(pCR).Results:From January 2019 through December 2021,a total of 53 patients were enrolled,7.5%of whom experienced grade 3-4 adverse events during *** pCR rate was 17.0%for the entire cohort,and the overall rate of postoperative complications was 37.7%(1.9%of gradeⅢa patients).The 3-year disease-free survival rate was 91.4%,and 23.5%(12/51)of the patients suffered from major low anterior resection syndrome(LARS).Postoperative complications were independently associated with major ***:For patients with mid-low rectal cancer with negative MRF,3 months of NCT were found to yield a favorable tumor response with acceptable *** fair long-term survival,the NCT regimen could be associated with low rates of perioperative complications as well as acceptable anal function.

关键词： Neoadjuvant chemotherapy rectal cancer mesorectal fascia disease-free survival anal function