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Molecular Mechanisms of Gut Microbiota-Associated colorectal Carcinogenesis

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Infectious Microbes & diseases 2020年第3期2卷 96-106页

作者： Yichang Shao Xun Zeng 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 HospitalZhejiang University School of MedicineHangzhouZhejiangChina Zhejiang University School of Medicine HangzhouZhejiangChina

colorectal cancer(CRC)is the cancer occurring in colon and rectum,and is the fourth leading cause of tumor-associated deaths *** a multi-etiological cancer,CRC could be induced by genetic and environmental factors,including unhealthy diet,irregular lifestyle,inappropriate inflammatory,and the dysbiosis of gut *** immunotherapy has been the most popular cancer therapy nowadays,the relationships among gut microbiota,host immune cells and CRC pathogenesis are widely *** constantly tried to figure out the underlying mechanisms involved to support the further therapeutic *** this review,we discuss the component shifts of gut microbiota in CRC patients compared with healthy people,summarize how immune cells participate in protecting host from pathogenic microbes,elaborate the molecular mechanisms involved in gut microbiota-associated carcinogenesis of colonic epithelial cells and look into how gut microbiota influence the CRC therapy.

关键词： gut microbiota colorectal cancer immune cells

“Watch and wait”strategy after neoadjuvant chemoradiotherapy in rectal cancer:opportunities and challenges

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Holistic Integrative Oncology 2023年第1期2卷 47-54页

作者： Yong Yang An Huang Zhuang Sun Hao-peng Hong Nam KYu Kim Jin Gu Department of Gastrointestinal Surgery Peking University Shougang HospitalBeijingChina Department of Gastrointestinal SurgeryⅢ Peking University Cancer Hospital&InstituteBeijingChina Department of Surgery Colorectal Division Yongin Severance HospitalCollege of MedicineSeoulSouth Korea center for precision diagnosis and treatment of colorectal cancer and inflammatory diseases Peking University Health Science CenterBeijingChina

The"watch and wait"(W&W)strategy has been widely used in rectal cancer patients who have achieved clinical complete response(cCR)after neoadjuvant chemoradiotherapy(nCRT),which can save them from surgery and improve their quality of ***,this strategy also has many unsolved practical problems,including the improvement of cCR/pCR rate,the search for efficient predictors,the standard follow-up and the methods of rescue surgery,*** sample size and more standardized clinical trials are still needed to obtain credible ***,we must rationally view the cCR after nCRT for middle and low rectal cancer,understand the risk of W&W strategy,and make a reasonable *** is particularly important to emphasize that we should actively carry out prospective multi-center clinical trials to produce high-level evidence suitable for Chinese characteristics,so that more rectal cancer patients can benefit from nCRT.

关键词： Watch and wait Rectal cancer Neoadjuvant chemoradiotherapy Clinical complete response

Improving the value of molecular testing:current status and opportunities in colorectal cancer precision medicine

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cancer Biology & Medicine 2024年第1期21卷 21-28页

作者： Haiyun Li Linwei Guo Chenchen Wang Xin Hu Ye Xu Department of colorectal Surgery Fudan University Shanghai Cancer CenterShanghai 200032China Department of Oncology Shanghai Medical CollegeFudan UniversityShanghai 200032China Department of Gastrointestinal Medical Oncology Fudan University Shanghai Cancer CenterShanghai 200032China precision cancer Medical center Affiliated with Fudan University Shanghai cancer center Shanghai 201315China

colorectal cancer(CRC)is the second leading cause of cancer-related deaths *** radical resection with adjuvant chemotherapy remains the primary treatment choice for CRC,but the 5-year postoperative survival rate is only approximately 60%,and approximately one-third of patients with CRC experience recurrence within 2 years of ***,the transformation of high-throughput sequencing has accelerated the development of precision *** example,KRAS mutations indicate resistance to anti-epidermal growth factor receptor(EGFR)-targeted therapies in ***,molecular-guided individualized therapy has brought new promise in major clinical areas and challenges,such as novel biomarkers predicting sensitivity and resistance to immunotherapy for microsatellite stable(MSS)CRC.

关键词： cancer chemotherapy colorectal

VDR–SOX2 signaling promotes colorectal cancer stemness and malignancy in an acidic microenvironment

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Signal Transduction and Targeted Therapy 2020年第1期5卷 852-864页

作者： Pei-Shan Hu Ting Li Jin-Fei Lin Miao-Zhen Qiu De-Shen Wang Ze-Xian Liu Zhan-Hong Chen Lu-Ping Yang Xiao-Long Zhang Qi Zhao Yan-Xing Chen Yun-Xin Lu Qi-Nian Wu Heng-Ying Pu Zhao-Lei Zeng Dan Xie Huai-Qiang Ju Hui-Yan Luo Rui-Hua Xu Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer MedicineSun Yat-sen University Cancer Center510060 GuangzhouPeople’s Republic of China precision diagnosis and treatment for Gastrointestinal cancer Chinese Academy of Medical Sciences510060 GuangzhouPeople’s Republic of China Department of Medical Oncology and Guangdong Key Laboratory of Liver Disease the Third Affiliated Hospital of Sun Yat-sen University510060 GuangzhouPeople’s Republic of China

The acidic tumor microenvironment provides an energy source driving malignant tumor *** of cells to an acidic environment leads to the emergence of cancer stem *** expression of the vitamin D receptor(VDR)is closely related to the initiation and development of colorectal carcinoma(CRC),but its regulatory mechanism in CRC stem cells is still *** study revealed that acidosis reduced VDR expression by downregulating peroxisome proliferator-activated receptor delta(PPARD)*** of VDR effectively suppressed the stemness and oxaliplatin resistance of cells in *** nuclear export signal in VDR was sensitive to acidosis,and VDR was exported from the *** immunoprecipitation(ChIP)and assay for transposase-accessible chromatin with high-throughput sequencing(ATAC-seq)analyses showed that VDR transcriptionally repressed SRY-box 2(SOX2)by binding to the vitamin D response elements in the promoter of SOX2,impairing tumor growth and drug *** demonstrated that a change in the acidic microenvironment combined with overexpression of VDR substantially restricted the occurrence and development of CRC in *** findings reveal a new mechanism by which acidosis could affect the stemness of CRC cells by regulating the expression of SOX2 and show that abnormal VDR expression leads to ineffective activation of vitamin D signaling,resulting in a lack of efficacy of vitamin D in antineoplastic process.

关键词： SOX2 vitamin colorectal

Phosphorylated NFS1 weakens oxaliplatin-based chemosensitivity of colorectal cancer by preventing PANoptosis

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Signal Transduction and Targeted Therapy 2022年第3期7卷 918-933页

作者： Jin-Fei Lin Pei-Shan Hu Yi-Yu Wang Yue-Tao Tan Kai Yu Kun Liao Qi-Nian Wu Ting Li Qi Meng Jun-Zhong Lin Ze-Xian Liu Heng-Ying Pu Huai-Qiang Ju Rui-Hua Xu Miao-Zhen Qiu Department of Medical Oncology Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineSun Yat-sen University510060 GuangzhouP.R.China Research Unit of precision diagnosis and treatment for Gastrointestinal cancer Chinese Academy of Medical Sciences510060 GuangzhouP.R.China Guangdong Provincial Key Laboratory of colorectal and Pelvic Floor Disease The Sixth Affiliated Hospital(Guangdong Gastrointestinal and Anal Hospital)Sun Yat-sen University510655 GuangzhouP.R.China Department of Pathology Sun Yat-sen University Cancer Center510060 GuangzhouP.R.China Department of Gastroenterology and Urology Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of MedicineCentral South University410013 ChangshaP.R.China Department of colorectal Surgery Sun Yat-sen University Cancer Center510060 GuangzhouP.R.China

Metabolic enzymes have an indispensable role in metabolic reprogramming,and their aberrant expression or activity has been associated with ***,targeting metabolic enzymes remains an attractive approach for treating tu... 详细信息

关键词： colorectal attractive Metabolic

KHK-A promotes fructose-dependent colorectal cancer liver metastasis by facilitating the phosphorylation and translocation of PKM2

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Acta Pharmaceutica Sinica B 2024年第7期14卷 2959-2976页

作者： Chaofan Peng Peng Yang Dongsheng Zhang Chi Jin Wen Peng Tuo Wang Qingyang Sun Zhihao Chen Yifei Feng Yueming Sun Department of General Surgery the First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China colorectal Institute of Nanjing Medical University Nanjing 210029China The First School of Clinical Medicine Nanjing Medical UniversityNanjing 210029China Jiangsu Province Engineering Research center of colorectal cancer precision Medicine and Translational Medicine Nanjing 210029China

Excessive fructose diet is closely associated with colorectal cancer(CRC)***,fructose’s specific function and precise mechanism in colorectal cancer liver metastasis(CRLM)is rarely ***,this study reported that the fructose absorbed by primary colorectal cancer could accelerate CRLM,and the expression of KHK-A,not KHK-C,in liver metastasis was higher than in paired primary ***,KHK-A facilitated fructose-dependent CRLM in vitro and in vivo by phosphorylating PKM2 at ***2 phosphorylated by KHK-A inhibited its tetramer formation and pyruvic acid kinase activity but promoted the nuclear accumulation of *** and aerobic glycolysis activated by nuclear PKM2 enhance CRC cells’migration ability and anoikis resistance during CRLM ***-46 treatment,targeting the phosphorylation of PKM2,inhibited the pro-metastatic effect of ***,c-myc activated by nuclear PKM2 promotes alternative splicing of KHK-A,forming a positive feedback loop.

关键词： CRC CRLM Fructose KHK-A PKM2

Temporal Change in treatment Patterns of Metastatic colorectal cancer and Its Association with Patient Survival:A Retrospective Cohort Study Based on an Intelligent Big-Data Platform

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Engineering 2021年第4期7卷 526-533页

作者： Zi-Xian Wang Yi-Chen Yao Zong-Jiong Mai Wu-Hao Lin You-Sheng Huang Ying Jin Hui-Yan Luo Dong-Sheng Zhang Feng-Hua Wang Feng Wang Gong Chen Pei-Rong Ding Yun-Fei Yuan Yu-Hong Li Jin-Hua Huang Zhi-Zhong Pan Rui-Hua Xu Department of Medical Oncology State Key Laboratory of Oncology in South China&Collaborative Innovation Center for Cancer MedicineSun Yat-sen University Cancer CenterGuangzhou 510060China Artificial Intelligence Laboratory Sun Yat-sen University Cancer CenterGuangzhou 510060China Research Unit of precision diagnosis and treatment for Gastrointestinal cancer Chinese Academy of Medical SciencesGuangzhou 510060China Department of colorectal Surgery Sun Yat-sen University Cancer CenterGuangzhou 510060China Department of Hepatobiliary Surgery Sun Yat-sen University Cancer CenterGuangzhou 510060China Department of Minimally Invasive Therapy Sun Yat-sen University Cancer CenterGuangzhou 510060China

There is a lack of high-quality,large-scale,real-world evidence from patients with metastatic colorectal cancer(mCRC),especially in *** remains unclear whether efforts to improve the quality of care for mCRC would improve patient survival outcomes in real-world *** the basis of an intelligent bigdata platform,we established a large-scale retrospective cohort of mCRC *** investigated the temporal changes in the systemic and local treatment(resection,ablation,or radiation to liver,lung,or extrahepatic and/or extrapulmonary metastases)patterns of mCRC,and whether these changes were associated with improved overall survival(OS)over *** July 2012 and December 2018,3403 eligible patients were included in this *** median OS was 42.8 months(95%confidence interval(CI),40.7–46.6)for the entire cohort,25.6 months(95%CI,24.7–26.9)for those treated with systemic therapy only,and not reached(95%CI,78.6 months–not reached)for those receiving local *** utility rate of local therapy increased continuously from 37.9%in 2012–2014 to 46.9%in 2017–2018.A dramatic increase in the utility rate of either cetuximab or bevacizumab was observed since 2017(39.9%,43.2%,and 60.3%in 2012–2014,2015–2016,and 2017–2018,respectively).Compared with 2012–2014,the OS of the entire population significantly improved in 2015–2016(hazard ratio(HR)=0.87(95%CI,0.78–0.99);P=0.034),but not for patients receiving systemic therapy only(HR=0.99(95%CI,0.86–1.14);P=0.889),whereas an improved OS was found in 2015–2018 for both the entire population(HR=0.75(95%CI,0.70–0.81);P<0.001)and for patients receiving systemic therapy only(HR=0.83(95%CI,0.77–0.91);P<0.001).In summary,the quality of care for mCRC,as indicated by the utility rate of targeted and local therapies,has been continuously improving over time in this study cohort,which is associated with continuously improving survival outcomes for these patients.

关键词： Metastatic colorectal cancer Real-world evidence treatment pattern Survival Big-data platform

ELP3 stabilizes c-Myc to promote tumorigenesis

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Journal of Molecular Cell Biology 2023年第9期15卷 40-52页

作者： Wentao Zhao Cong Ouyang Chen Huang Jiaojiao Zhang Qiao Xiao Fengqiong Zhang Huihui Wang Furong Lin Jinyang Wang Zhanxiang Wang Bin Jiang Qinxi Li State Key Laboratory of Cellular Stress Biology School of Life SciencesFaculty of Medicine and Life SciencesXiamen UniversityXiamen 361102China Department of Neurosurgery and Department of Neuroscience Fujian Key Laboratory of Brain Tumors Diagnosis and Precision TreatmentXiamen Key Laboratory of Brain Centerthe First Affiliated Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamen 361003China

ELP3,the catalytic subunit of the Elongator complex,is an acetyltransferase and associated with tumor ***,the detail of ELP3 oncogenic function remains largely ***,we found that ELP3 stabilizes c-Myc to promote tumorigenesis in an acetyltransferase-independent ***,ELP3 competes with the E3-ligase FBXW7βfor c-Myc binding,resulting in the inhibition of FBXW7β-mediated ubiquitination and proteasomal degradation of ***3 knockdown diminishes glycolysis and glutaminolysis and dramatically retards cell proliferation and xenograft growth by downregulating c-Myc,and such effects are rescued by the reconstitution of c-Myc ***,ELP3 and c-Myc were found overexpressed with a positive correlation in colorectal cancer and hepatocellular *** together,we elucidate a new function of ELP3 in promoting tumorigenesis by stabilizing c-Myc,suggesting that inhibition of ELP3 is a potential strategy for treating c-Myc-driven carcinomas.

关键词： ELP3 c-Myc FBXW7 Elongator

Endoscopic stricturotomy in the treatment of anastomotic strictures in inflammatory bowel disease(IBD)and non-IBD patients

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Gastroenterology Report 2020年第2期8卷 143-150,I0002,I0003页

作者： Long-Juan Zhang Nan Lan Xian-Rui Wu Bo Shen Laboratory of General Surgery the First Affiliated HospitalSun Yat-Sen UniversityGuangzhouGuangdongP.R.China center for inflammatory Bowel Disease Digestive Disease and Surgery InstituteThe Cleveland Clinic FoundationClevelandOHUSA Department of colorectal Surgery and Guangdong Provincial Key Laboratory of colorectal and Pelvic Floor diseases the Sixth Affiliated HospitalSun Yat-Sen UniversityGuangzhouGuangdongP.R.China

Backgrounds:Endoscopic stricturotomy(ESt)has been shown to be effective in treating inflammatory bowel disease(IBD)-associated anastomotic ***,the outcome of ESt in benign,non-IBD conditions has not been *** aim of this study was to evaluate the outcome of ESt in the management of IBD and non-IBD-associated ***:Data of all consecutive IBD and non-IBD patients with benign anastomotic strictures treated with ESt from 2009 to 2016 were *** primary outcomes were surgery-free survival and procedure-related ***:A total of 49 IBD and 15 non-IBD patients were included in this *** IBD group included 25 patients with Crohn’s disease and 24 with ulcerative colitis and ileal *** diseases in the non-IBD group included colorectal cancer(n=7),diverticulitis(n=5),large bowel prolapse(n=2),and constipation(n=1).Immediate technical success was achieved in all patients in both *** complications occurred on five occasions(4.7%per procedure)in the IBD group,while no complication occurred in the non-IBD group(P=0.20).Stricture improvement on follow-up endoscopy was found in 10(20.4%)and 5(33.3%)patients in the IBD and non-IBD groups,respectively(P=0.32).Six(12.2%)patients in the IBD group and four(26.7%)patients in the non-IBD group eventually required stricture-related surgery(P=0.23).IBD patients appeared to have a higher tendency formaintaining surgery-free after the procedure than non-IBD patients(P=0.08).Conclusions:Endoscopic stricturotomy was shown to have comparable outcomes,though non-IBD patients seem to have a higher need for subsequent surgery but a lower complication rate than IBD patients.

关键词： endoscopic stricturotomy inflammatory bowel disease anastomotic stricture