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Panax notoginseng saponins prevent colitis-associated colorectal cancer via inhibition IDO1 mediated immune regulation

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Chinese Journal of Natural Medicines 2022年第4期20卷 258-269页

作者： LI Xue-Ming YUAN Ding-Yi LIU Ya-Hui ZHU Lei QIN Hong-Kun YANG Yu-Bing LI Yan YAN Fang WANG Ya-Jing Department of physiology School of Basic Medicine and Clinical PharmacyChina Pharmaceutical UniversityNanjing 210009China Department of Pharmaceutical Analysis School of pharmacologyChina Pharmaceutical UniversityNanjing 210009China Department of Chronic Communicable Disease Jiangsu Provincial Center for Disease Prevention and ControlNanjing 210009China

colorectal cancer(CRC)is the third most lethal cancer and leading cause of cancer mortality worldwide.A key driver of CRC development is colon inflammatory responses especially in patients with inflammatory bowl disease(IBD).It has been proved that Panax notoginseng saponins(PNS)have anti-inflammatory,anti-oxidant and anti-tumor *** chemopreventive and immunomodulatory functions of PNS on colitis-associated colorectal cancer(CAC)have not been *** present study was designed to study the potential protective effects of PNS on AOM/DSS-induced CAC mice to explore the possible mechanism of PNS against *** study showed that PNS significantly alleviated colitis severity and prevented the occurrence of *** assays revealed that PNS relieved immunosuppression of Treg cells in the CAC microenvironment by inhibiting the expression of IDO 1 mediated directly by signal transducer and activator of transcription 1(STAT1)rather than phosphorylated ***,Rhl,one of the PNS metabolites,exhibited the best inhibitory effect on IDO1 enzyme *** study showed that PNS exerted significant chemopreventive function and immunomodulatory properties on *** could reduce macrophages accumulation and Treg cells differentiation to reshape the immune microenvironment of *** findings provided a promising approach for CAC intervention.

关键词： Panax notoginseng saponins colitis-associated colorectal cancer Chemoprevention Treg cells IDO1

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Update and latest advances in mechanisms and management of colitis-associated colorectal cancer

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World Journal of Gastrointestinal Oncology 2023年第8期15卷 1317-1331页

作者： Wan-Yue Dan Guan-Zhou Zhou Li-Hua Peng Fei Pan Department of Gastroenterology and Hepatology The First Medical CenterChinese PLA General HospitalBeijing 100853China Medical School Nankai UniversityTianjin 300071China

colitis-associated colorectal cancer(CAC)is defined as a specific cluster of colorectal cancers that develop as a result of prolonged colitis in patients with inflammatory bowel disease(IBD).Patients with IBD,including ulcerative colitis and Crohn’s disease,are known to have an increased risk of developing *** the incidence of CAC has significantly decreased over the past few decades,individuals with CAC have increased mortality compared to individuals with sporadic colorectal cancer,and the incidence of CAC increases with *** inflammation is generally recognized as a major contributor to the pathogenesis of *** has been shown to progress from colitis to dysplasia and finally to *** evidence suggests that multiple immune-mediated pathways,DNA damage pathways,and pathogens are involved in the pathogenesis of *** the past decade,there has been an increasing effort to develop clinical approaches that could help improve outcomes for CAC *** surveillance plays an important role in reducing the risk of advanced and interval *** is generally recommended that CAC patients undergo endoscopic removal or *** review summarizes the current understanding of CAC,particularly its epidemiology,mechanisms,and *** focuses on the mechanisms that contribute to the development of CAC,covering advances in genomics,immunology,and the microbiome;presents evidence for management strategies,including endoscopy and colectomy;and discusses new strategies to interfere with the process and development of *** scientific findings will pave the way for the management of CAC in the near future.

关键词： colitis-associated colorectal cancer Inflammatory bowel disease Colonoscopic surveillance Epidemiology Mechanisms Management

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Early detection of ulcerative colitis-associated colorectal cancer

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Gastroenterology Report 2018年第2期6卷 83-92,I0001页

作者： Yu Zhen Chengxin Luo Hu Zhang Department of Gastroenterology West China HospitalSichuan UniversityChengduSichuan 610041China

colitis-associated colorectal cancer(CACC)is one of the most serious complications of inflammatory bowel disease(IBD),particularly in ulcerative colitis(UC);it accounts for approximately 15%of all-causes mortality among IBD *** CACC shows a worse prognosis and higher mortality than sporadic colorectal cancer,early detection is *** is primarily recommended for surveillance and several advanced endoscopic imaging techniques are *** addition,recent studies have reported on attempts to develop clinically relevant biomarkers for surveillance using various biosamples,which may become high-performance screening tools in the future,so the best approach and technique for cancer surveillance in long-standing UC patients remain under *** review gives a comprehensive description and summary about what progress has been made in terms of early CACC detection.

关键词： Ulcerative colitis colitis-associated colorectal cancer endoscopy biomarker surveillance

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Immune reaction and colorectal cancer:Friends or foes?

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World Journal of Gastroenterology 2014年第35期20卷 12407-12419页

作者： Vincenzo Formica Vittore Cereda Antonella Nardecchia Manfredi Tesauro Mario Roselli Medical Oncology Unit ‘Tor Vergata’ University Hospital Internal Medicine Department ‘Tor Vergata’ University Hospital

The potential clinical impact of enhancing antitumor immunity is increasingly recognized in oncology therapeutics for solid *** cancer is one of the most studied neoplasms for the tumor-host immunity *** immune cell populations involved in such a relationship and their prognostic role in colorectal cancer development have clearly been identified,still no approved therapies based on host immunity intensification have so far been introduced in clinical ***,a recognized risk in enhancing immune reaction for colitis-associated colorectal cancer development has limited the emphasis of this *** aim of the present review is to discuss immune components involved in the host immune reaction against colorectal cancer and analyze the fine balance between pro-tumoral and anti-tumoral effect of immunity in this model of disease.

关键词： colitis-associated colorectal cancer Antitumor immunity Innate immunity Adaptive immunity

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Involvement of integrin-activating peptides derived from tenascin-C in colon cancer progression

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World Journal of Gastrointestinal Oncology 2021年第9期13卷 980-994页

作者： Motomichi Fujita Hideo Suzuki Fumio Fukai Department of Molecular Patho-Physiology Tokyo University of ScienceNoda 278-8510ChibaJapan Department of Gastroenterology University of TsukubaTsukuba 305-8575IbarakiJapan

Tenascin-C(TNC)is an adhesion modulatory protein present in the extracellular matrix that is highly expressed in several malignancies,including colon *** TNC is considered a negative prognostic factor for cancer patients,the substantial role of the TNC molecule in colorectal carcinogenesis and its malignant progression is poorly *** previously found that TNC has a cryptic functional site and that a TNC peptide containing this site,termed TNIIIA2,can potently and persistently activate *** contrast,the peptide FNIII14,which contains a cryptic bioactive site within the fibronectin molecule,can inactivate *** review presents the role of TNC in the development of colitis-associated colorectal cancer and in the malignant progression of colon cancer,particularly the major involvement of its cryptic functional site *** propose new possible prophylactic and therapeutic strategies based on inhibition of the TNIIIA2-induced beta1-integrin activation by peptide FNIII14.

关键词： Tenascin-C TNIIIA2 Beta1-integrin Integrin activation colitis-associated colorectal cancer Colon cancer

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NEDD4L mediates intestinal epithelial cell ferroptosis to restrict IBDs and tumorigenesis in humans and mice

NEDD4L mediates intestinal epithelial cell ferroptosis to re...

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浙江省免疫学会第十三次学术大会

作者： Jingjing Liang Ning Wang Xiang An Haofei Wang Hui Liu Yu Jiang Huan Li Wang Yingmei Zengfeng Xin Ting Zhang Xiaojian Wang Wenlong Lin Hangzhou City University and Institute of Immunology Zhejiang University School of Medicine Institute of Basic and Translational Medicine Xi'an Medical University Department of Medical Oncology the Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)Institute of Basic Medicine and Cancer (IBMC)Chinese Academy of Sciences Department of Clinical Laboratory Medicine Second Affiliated HospitalSchool of MedicineZhejiang University State Key Laboratory of cancer Biology Department of PathologyXijing Hospital and School of Basic Medicinethe Fourth Military Medical University Department of Orthopedic Surgery The Second Affiliated HospitalZhejiang University School of Medicine Department of Radiation Oncology The Second Affiliated HospitalZhejiang University School of Medicine

Background:Various factors such as genetic variation,environment, diet,and intestinal flora play a key role in maintaining the homeostasis of the *** intestinal homeostasis could cause intestinal inflammatory diseases,including Crohn's disease(CD),ulcerative colitis(UC),and even colorectal cancer(CRC).It has been reported that many key genes' loss or gain function results in severe dysregulated intestinal ***,the regulatory role of NEDD4 L in IBD and colitis-associated colorectal cancer(CAC) remains ***:Neural precursor cells expressed developmentally down-regulated 4-like protein,NEDD4 L(NEDD4-2) appear to control the ubiquitination of various membrane proteins,essential for maintaining cell *** NEDD4 L gene is highly expressed in intestinal systems,however,its role in the homeostasis of the GI tract remains *** sought to identify the roles of NEDD4 L in maintaining homeostasis of the GI *** and methods:The expression of NEDD4 L was determined by immnohistochemistry and western blot ***4 L knockout and wild-type mice were administered dextran sulfate sodium(DSS),2,4,6-trinitrobenzene sulfonic acid(TNBS),or azoxymethane(AOM)/DSS to induce experimental colitis or colorectal cancer,and the mice were assessed based on colitis symptoms and biochemical *** mechanism was analyzed using immunoprecipitation and ubiquitination ***:Our research demonstrated that NEDD4 L,a kind of HECT family E3 ubiquitin ligase,plays an important role in maintaining intestinal ***4 L gene and protein expression are significantly inhibited in intestinal epithelial cells(IECs) of patients with UC,CD,and ***4 L global knockout or NEDD4 L deficiency in IECs significantly exacerbated DSS-/TNBS-induced colitis and AOM/DSS-induced colorectal ***,NEDD4 L deficiency in IECs reduces the protein expression of soluble amino acid transport protein SLC3 A2 wit

关键词： intestinal inflammatory diseases colitis-associated colorectal cancer NEDD4L ferroptosis

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Complement activation promotes colitis-associated carcinogenesis through activating intestinal IL-1β/IL-17A axis

Complement activation promotes colitis-associated carcinogen...

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第十届全国免疫学学术大会

作者： Guojiang Chen Chang Ning Yuanyuan Li Gencheng Han Renxi Wang He Xiao Chunmei Hou Beifen Shen Jiannan Feng Yan Li Department of Immunology Institute of Basic Medical Sciences Academy of Military Medical Sciences Department of Oncology the 161st Hospital of the PLA Laboratory of Cellular and Molecular Immunology Medical School of Henan University

colitis-associated colorectal cancer(CAC)is the most serious complication of inflammatory bowel disease(IBD).Excessive complement activation has been shown to be involved in the pathogegesis of ***,its role in the development of CAC is largely ***,using a CAC model induced by combined administration of azoxymethane(AOM)and dextran sulfate sodium(DSS),we demonstrated that complement activation was required for CAC *** in key components of complement(e.g.C3,C5 or C5a receptor)rendered tumor repression in mice subjected to AOM/*** investigation revealed that complement ablation dramatically reduced proinflammatory cytokine interleukin(IL)-1βlevels in the colonic tissues,which was mainly produced by infiltrating ***-1βpromoted colon carcinogenesis by eliciting IL-17 response in intestinal myeloid ***,complement-activation product C5a represented a potent inducer for IL-1βin neutrophil,which accounted for down-regulation of IL-1βlevels in the employed complement-deficient ***,our study proposes a pro-tumorigenic role of complement in inflammationrelated colorectal cancer and that the therapeutic strategies targeting complement may be beneficial for the treatment of CAC in clinic.

关键词： Complement colitis-associated colorectal cancer IL-1β IL-17A intestinal myeloid cell

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