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Probiotics and postbiotics in colorectal cancer:Prevention and complementary therapy

World Journal of Gastroenterology 2022年第27期28卷 3370-3382页

作者： Monika Kvakova Anna Kamlarova Jana Stofilova Veronika Benetinova Izabela Bertkova center of Clinical and Preclinical Research MEDIPARK Faculty of MedicineP.J.Safarik University in KosiceKosice 04011Slovakia

colorectal cancer(CRC)is a leading cause of human mortality *** conventional anticancer therapy not always being effective,there is growing interest in innovative“drug-free”cancer treatments or interventions that improve the efficacy of established *** is associated with microbiome alterations,a process known as dysbiosis that involves depletion and/or enrichment of particular gut bacterial species and their metabolic *** patient treatment with traditional probiotics(with or without prebiotics),nextgeneration probiotics(NGP),or postbiotics represents a potentially effective and accessible complementary anticancer strategy by restoring gut microbiota composition and/or by signaling to the *** this capacity,restoration of the gut microbiota in cancer patients can stabilize and enhance intestinal barrier function,as well as promote anticarcinogenic,anti-inflammatory,antimutagenic or other biologically important biochemical pathways that show high specificity towards tumor *** benefits of traditional probiotics,NGP,and postbiotics include modulating gut microbiota composition and function,as well as the host inflammatory *** application in CRC prevention is highlighted in this review,where we consider supportive in vitro,animal,and clinical *** on emerging research,NGP and postbiotics hold promise in establishing innovative treatments for CRC by conferring physiological functions via the production of dominant natural products and metabolites that provide new host-microbiota signals to combat *** favorable results have been reported,further investigations focusing on strain and dose specificity are required to ensure the efficacy and safety of traditional probiotics,NGP,and postbiotics in CRC prevention and treatment.

关键词： colorectal cancer Traditional probiotics Next-generation probiotics Postbiotics Gut microbiota

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Single-cell analyses reveal cannabidiol rewires tumor microenvironment via inhibiting alternative activation of macrophage and synergizes with anti-PD-1 in colon cancer

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Journal of Pharmaceutical Analysis 2023年第7期13卷 726-744页

作者： Xiaofan Sun Lisha Zhou Yi Wang Guoliang Deng Xinran Cao Bowen Ke Xiaoqi Wu Yanhong Gu Haibo Cheng Qiang Xu Qianming Du Hongqi Chen Yang Sun Department of Rheumatology and Immunology Nanjing Drum Tower HospitalThe Affiliated Hospital of Nanjing University Medical SchoolNanjing UniversityNanjing210008China State Key Laboratory of Pharmaceutical Biotechnology School of Life SciencesNanjing UniversityNanjing210023China Colon and Rectal Surgery Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese MedicineNanjing210001China Laboratory of Anesthesia and Critical Care Medicine Department of AnesthesiologyTranslational Neuroscience CenterWest China Hospital and State Key Laboratory of BiotherapySichuan UniversityChengdu610044China Genergy Bio-technology(Shanghai)Co. LtdShanghai200241China The First Affiliated Hospital of Nanjing Medical University Jiangsu Province HospitalNanjing210029China Jiangsu Collaborative Innovation center of Traditional Chinese Medicine in Prevention and treatment of Tumor The First Clinical College of Nanjing University of Chinese MedicineNanjing210023China General Clinical Research center Nanjing First HospitalNanjing Medical UniversityNanjing210006China School of Basic Medicine&Clinical Pharmacy China Pharmaceutical UniversityNanjing210009China Department of General Surgery Shanghai Jiao Tong University Affiliated Sixth People's HospitalShanghai200030China Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy Xuzhou Medical UniversityXuzhouJiangsu221004China

colorectal tumors often create an immunosuppressive microenvironment that prevents them from responding to ***(CBD)is a non-psychoactive natural active ingredient from the cannabis plant that has various pharmacological effects,including neuroprotective,antiemetic,anti-inflammatory,and antineoplastic *** study aimed to elucidate the specific anticancer mechanism of CBD by single-cell RNA sequencing(scRNA-seq)and single-cell ATAC sequencing(scATAC-seq)***,we report that CBD inhibits colorectal cancer progression by modulating the suppressive tumor microenvironment(TME).Our single-cell transcriptome and ATAC sequencing results showed that CBD suppressed M2-like macrophages and promoted M1-like macrophages in tumors both in strength and ***,CBD significantly enhanced the interaction between M1-like macrophages and tumor cells and restored the intrinsic anti-tumor properties of macrophages,thereby preventing tumor ***,CBD altered the metabolic pattern of macrophages and related anti-tumor signaling *** found that CBD inhibited the alternative activation of macrophages and shifted the metabolic process from oxidative phosphorylation and fatty acid oxidation to glycolysis by inhibiting the phosphatidylinositol 3-kinase-protein kinase B signaling pathway and related downstream target ***,CBD-mediated macrophage plasticity enhanced the response to anti-programmed cell death protein-1(PD-1)immunotherapy in xenografted *** together,we provide new insights into the anti-tumor effects of CBD.

关键词： scRNA-seq scATAC-seq Cannabidiol colorectal cancer Tumor microenvironment Macrophage

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Green Tea Polyphenols Mediated Apoptosis in Intestinal Epithelial Cells by a Fadd-Dependent Pathway

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Journal of cancer Therapy 2010年第3期1卷 105-113页

作者： Helieh S. Oz Jeffrey L. Ebersole center for Oral Health Research College of Dentistry University of Kentucky Medical Center Lexington KY.

colorectal cancer is the most common malignant complication in patients with chronic inflammatory bowel disease (IBD). In addition, these patients are at risk for developing painful complications during chemotherapy due to cytotoxic effects of drugs currently in use. Past studies have suggested a protective effect of tea consumption on gastrointestinal (GI) malignancies. Green tea polyphenols (GrTP) inhibited carcinogen-induced GI tumors in rodents and induced apoptosis in various carcinoma cell lines. We hypothesized that GrTP and its polyphenolic compounds regulate apoptosis in the intestinal epithelia. In this study, the effects of GrTP and its polyphenolics on apoptosis was evaluated in intestinal epithelial, IEC-6, cells grown to 85% confluency. GrTP (400-800 mg/ml) induced DNA fragmentation in a dose dependent fashion. Higher concentrations (> 800 mg/ml) induced a mixed apoptosis and cytolysis. Epithelial cells exposed to GrTP and a major polyphenol, EGCG, but not EGC or EC, increased caspase activities in a time and dose dependent manner. The caspase inhibitors rescued cells from GrTP and EGCG-induced cell death. Concomitantly, GrTP resulted in activation of fatty acid synthase (Fas)-associated protein with death domain (FADD) and recruitment to Fas/CD95 domain 30 minutes following treatment. While GrTP also blocked NF-?B activation, an NF-?B inhibitor (MG132) only promoted cytolysis. In conclusion, these data demonstrated GrTP and EGCG induced apoptosis in intestinal epithelia mediated by caspase-8 through a FADD dependent pathway. Future investigation may warrant preventive as well as therapeutic strategies for GrTP in GI malignancy.

关键词： Intestinal Epithelial Cells Green Tea Polyphenols EGCG Apoptosis

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How can colorectal neoplasms be treated during colonoscopy?

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World Journal of Gastroenterology 2005年第18期11卷 2806-2810页

作者： Yu-Pin Ho Chen-Ming Hsu Jau-Min Lien Shui-Yi Tung Cheng-Shyong Wu Digestive Therapeutic Endoscopic center Department of Gastroenterology Chang-Gung Memorial Hospital Linkou Medical Center 5 Fushin Street Kweishan Taoyuan Taiwan China

AIM: For many physicians who ordinarily treat patients with colonic diseases, colonoscopy is considered a prime study interest. Developments in colonoscopic equipment and methods have led to a large number of endoscopic diagnoses and treatment for colorectal neoplasms. The purpose of this investigation is to evaluate the efficacy and outcomes of endoscopic treatment for colorectal neoplastic ***: From September 1999 to May 2003, 11 447 consecutive colonoscopic examinations in 9 864 patients were gathered; totaling 5 502 endoscopic treatments for colorectal neoplasms. Macroscopic characteristics of the neoplasms were classified into protruded (n = 3 953), sessile (n = 1 402), lateral spreading tumor (n = 139) and depressed lesions (n = 8). Snare polypectomy was conducted in 3 984 lesions, hot forcep removal in 1 368 lesions, and endoscopic mucosal resection in 150 ***: Histological diagnoses were 4 596 neoplastic lesions (4 376 adenomas and 220 adenocarcinomas) and 906 non-neoplastic lesions (891 hyperplastic and 15 inflammatory polyps). For the adenocarcinoma group, 31 instances involved submucosal invasion or resection margin, who received further operations, while 13 surgical specimens discovered no residual tumors. Three perforations and 96 bleedings were found following endoscopic treatment. No procedure-related mortality was found and no recurrent malignancy was found after 1456 mo ***: To lower the incidence and mortality of colorectal cancer, endoscopic treatment for colorectalneoplasms is a simple and safe procedure.

关键词： Colonoscopy Snare Hot forcep Endoscopic mucosal resection

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Network Pharmacology of Xian-Lian-Jie-Du Decoction in Ameliorating colorectal cancer

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World Journal of Traditional Chinese Medicine 2024年第1期10卷 83-92页

作者： Ming-Xia Zhao Cheng-Lin Song Qin-Chang Zhang Hao-Jie Du Shu-Qiong Zhang Yu-Xian Shen Yang Sun Hai-Bo Cheng Wen Lv Department of Pharmacy School of Basic Medical SciencesAnhui Medical UniversityHefeiAnhuiChina Department of Biopharmaceutical Research Institute Anhui Medical UniversityHefeiAnhuiChina Department of Pharmaceutical Analysis State Key Laboratory of Natural and Biomimetic DrugsSchool of Pharmaceutical SciencesPeking UniversityBeijingChina Jiangsu Collaborative Innovation center of Traditional Chinese Medicine in Prevention and treatment of Tumor First Clinical CollegeNanjing University of Chinese MedicineNanjingJiangsuChina Deparment of Biotechnology and Pharmaceutical Sciences State Key Laboratory of Pharmaceutical BiotechnologySchool of Life SciencesNanjing UniversityNanjingJiangsuChina Deparment of Gynecology Institute of Traditional Chinese Medicine of Zhejiang ProvinceTongde Hospital of Zhejiang ProvinceHangzhouZhejiangChina

Objective:In this study,we screened for therapeutic targets of the Xian-Lian-Jie-Du decoction(XLJDD)for colorectal cancer(CRC)and explored the underlying mechanisms using network pharmacology ***:Genes associated with CRC were collected from the Gene Cards *** names of the active compounds of XLJDD were used as keywords in the“chemical name”in the Traditional Chinese Medicine Systems Pharmacology(TCMSP)database to search the *** protein-protein interaction(PPI)network was constructed using Cytoscape *** Ontology functional enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were performed to identify key target ***:A total of 234 XLJDD-related targets and 250 cross-targets between XLJDD and CRC were collected based on the TCMSP and HIT 2.0 databases.A PPI network constructed based on the STRING database revealed interactions for all 250 *** network results revealed TP53,MYC,CCND1,AKT1,CASP3,and STAT3 as core potential *** pathway analysis of the 250 potential XLJDD targets for CRC in the Metascape database was performed using RStudio *** top 12 gene ratio aggregated analysis results were visualized in bubble *** interleukin(IL)-17 signaling pathway had the highest correlation with the tumor necrosis factor(TNF)signaling ***:XLJDD may be effective in ameliorating CRC by controlling inflammatory factors related to the IL-17 and TNF pathways and targeting proto-oncogenes and tumor suppressor genes,including MYC,CCND1,CTNNB1,and TP53.

关键词： colorectal cancer network pharmacology Xian-Lian-Jie-Du decoction

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Spontaneous Tumor Lysis Syndrome and Secondary Thrombotic Thrombocytopenic Purpura in Early Stage colorectal cancer

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Chinese Journal of Clinical Oncology 2008年第2期5卷 150-153页

作者： Saad Usmani Joel Appel Zainab Shahid Husain Saleh Hematology-Oncology University of Connecticut Health Center Department of Internal Medicine/HematologyOncology Sinai-Grace HospitalWayne State University Department of Internal Medicine Sinai-Grace Hospital/Detroit Medical CenterWayneState University Department of Pathology Sinai-Grace Hos-pital/Detroit Medical CenterAssociate Pro-fessor of PathologyWayne State University

Introduction Acute tumor lysis syndrome （ATLS） is a well-described oncological emergency that is usually associated with hematological malignancies complicated by treatment. It is typically related to a high tumor burden, rapidly growing and chemosensitive malignancies. ATLS is characterized by the presence of hyperphosphatemia, hyperuricemia, hyperkalemia, hypocalcemia and acute renal failure. The administration of cytotoxic chemotherapy causes tumor death and tissue necrosis which leads to release of inflammatory mediators precipitating this syndrome. However, it has been rarely reported in hematological malignancies without administration of chemotherapy, and has been referred to as spontaneous tumor lysis syndrome （STLS）. STLS is even more infrequent in solid tumors.

关键词： tumor lysis syndrome thrombotic thrombocytopenic purpura colorectal cancer acute renal failure.

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Molecular determinants of response to 5-fluorouracil-based chemotherapy in colorectal cancer: The undisputable role of microribonucleic acids

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World Journal of Gastrointestinal Oncology 2020年第9期12卷 942-956页

作者： Amirsaeed Sabeti Aghabozorgi Mostafa Moradi Sarabi Reza Jafarzadeh-Esfehani Shabnaz Koochakkhani Marziyeh Hassanzadeh Soudabeh Kavousipour Ebrahim Eftekhar Medical Genetics Research center Mashhad University of Medical SciencesMashhad ***Iran Department of Biochemistry and Genetics School of MedicineLorestan University of Medical SciencesKhorramabad 381251698Iran Department of Medical Genetics Faculty of MedicineMashhad University of Medical SciencesMashhad ***Iran Molecular Medicine Research center Hormozgan Health InstituteHormozgan University of Medical SciencesBandar Abbas ***Iran

5-flurouracil(5-FU)-based chemotherapy is the main pharmacological therapy for advanced colorectal cancer(CRC).Despite significant progress in the treatment of CRC during the last decades,5-FU drug resistance remains the most important cause of failure in CRC *** to 5-FU is a complex and multistep *** mechanisms including microsatellite instability,increased expression level of key enzyme thymidylate synthase and its polymorphism,increased level of 5-FU-activating enzymes and mutation of TP53 are proposed as the main determinants of resistance to 5-FU in CRC ***,microribonucleic acids(miRNA)and their alterations were found to have a crucial role in 5-FU *** this regard,the miRNA-mediated mechanisms of 5-FU drug resistance reside among the new fields of pharmacogenetics of CRC drug response that has not been completely *** of the biological markers that are related to response to 5-FU-based chemotherapy is an emerging field of precision *** approach will have an important role in defining those patients who are most likely to benefit from 5-FU-based chemotherapy in the ***,the identification of 5-FU drug resistance mechanisms is an essential step to predict and eventually overcome *** the present comprehensive review,we will summarize the latest knowledge regarding the molecular determinants of response to 5-FU-based chemotherapy in CRC by emphasizing the role of miRNAs.

关键词： 5-flurouracil colorectal cancer Chemotherapy resistance,Thymidylate synthase Microsatellite instability Micro-ribonucleic acid TP53

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From macroautophagy to mitophagy:Unveiling the hidden role of mitophagy in gastrointestinal disorders

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World Journal of Gastroenterology 2024年第23期30卷 2934-2946页

作者： Duo-Lun Gao Meng-Ran Lin Nan Ge Jin-Tao Guo Fan Yang Si-Yu Sun Department of Gastroenterology Engineering Research Center of Ministry of Education for Minimally Invasive Gastrointestinal Endoscopic TechniquesShengjing Hospital of China Medical UniversityShenyang 110004Liaoning ProvinceChina

In this editorial,we comment on an article titled“Morphological and biochemical characteristics associated with autophagy in gastrointestinal diseases”,which was published in a recent issue of the World Journal of *** focused on the statement that“autophagy is closely related to the digestion,secretion,and regeneration of gastrointestinal cells”.With advancing research,autophagy,and particularly the pivotal role of the macroautophagy in maintaining cellular equilibrium and stress response in the gastrointestinal system,has garnered extensive ***,the significance of mitophagy,a unique selective autophagy pathway with ubiquitin-dependent and independent variants,should not be *** recent decades,mitophagy has been shown to be closely related to the occurrence and development of gastrointestinal diseases,especially inflammatory bowel disease,gastric cancer,and colorectal *** interplay between mitophagy and mitochondrial quality control is crucial for elucidating disease mechanisms,as well as for the development of novel treatment *** the pathogenesis behind gastrointestinal diseases and providing individualized and efficient treatment for patients are subjects we have been *** article reviews the potential mechanism of mitophagy in gastrointestinal diseases with the hope of providing new ideas for diagnosis and treatment.

关键词： Mitophagy Gastrointestinal diseases Parkin Autophagic receptor colorectal cancer Gastric cancer inflammatory bowel disease

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Molecular profiling and patient selection for the multimodal approaches for patients with resectable colorectal liver metastases

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Hepatobiliary Surgery and Nutrition 2024年第2期13卷 273-292页

作者： Raphael L.C.Araujo Leonardo G.Fonseca Raphael Oliveira Silva Marcelo Moura Linhares Pedro L.S.Uson Junior Department of Surgery Universidade Federal de São PauloSão PauloSPBrazil Hospital e Maternidade Brasil-Rede D’Or São Luiz Santo AndréSPBrazil Department of Oncology Hospital Israelita Albert EinsteinSão PauloSPBrazil Department of Oncology Instituto do Cancer do Estado de São PauloUniversity of Sao PauloSão PauloSPBrazil Department of Oncology Hospital Ministro Costa CavalcantiFoz do IguaçuPRBrazil center for Personalized Medicine Hospital Israelita Albert EinsteinSão PauloSPBrazil

colorectal cancer represents the third most common cancer and about 20%are diagnosed with synchronous metastatic *** a historical point of view,surgery remains the mainstream treatment for resectable colorectal liver metastases(CRLM).Furthermore,disease outcomes are improving due significant advances in systemic treatments and diagnostic ***,the optimal timing for neoadjuvant chemotherapy or upfront surgery for CRLM has not yet been established and remains an open ***,patient selection combining image workouts,time of recurrence,positive lymph nodes,and molecular biomarkers can improve the decision-making ***,molecular profiling is rising as a promising field to be incorporated in the multimodal approach and guide patient selection and sequencing of *** biomakers,genetic profiling,and circulating tumor DNA have been used to offer as much personalized treatment as possible,based on the precision oncology concept of tailored care rather than a guideline-based *** review article discusses the role of molecular pathology and biomarkers as prognostic and predictor factors in the diagnosis and treatment of resectable CRLM.

关键词： colorectal liver metastases(CRLM) surgery chemotherapy molecular pathology circulating tumor DNA tumor markers

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ROS and Lipid Droplet accumulation induced by high glucose exposure in healthy colon and colorectal cancer Stem Cells

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Genes & diseases 2020年第4期7卷 620-635页

作者： Luca Tirinato Francesca Pagliari Simone Di Franco Elisa Sogne Maria Grazia Marafioti Jeanette Jansen Andrea Falqui Matilde Todaro Patrizio Candeloro Carlo Liberale Joao Seco Giorgio Stassi Enzo Di Fabrizio Biomedical Physics in Radiation Oncology DKFZ(German Cancer Research Center)69120 HeidelbergGermany Physical Science and Engineering(PSE)Division King Abdullah University of Science and Technology(KAUST)ThuwalSaudi Arabia Department of Experimental and Clinical Medicine University“Magna Graecia”of Catanzaro88100 Loc.GermanetoCatanzaroItaly Biological and Environmental Sciences and Engineering(BESE)Division King Abdullah University of Science and Technology(KAUST)Thuwal 23955-6900Saudi Arabia Cellular and Molecular Pathophysiology Laboratory Department of SurgicalOncological and Stomatological SciencesUniversity of PalermoPalermoItaly Ruprecht Karls University Heidelberg Department of Physics69120 HeidelbergGermany Department of Health Promotion Mother and Child CareInternal Medicine and Medical Specialties(PROMISE)University of PalermoPalermoItaly

Lipid Droplets(LDs)are emerging as crucial players in colon cancer development and *** expression has been associated with high tumorigenicity in cancer Stem Cells(CSCs),so that they have been proposed as a new functional marker in colorectal cancer Stem Cells(CR-CSCs).They are also indirectly involved in the modulation of the tumor microenvironment through the production of pro-inflammatory *** is growing evidence that a possible connection between metabolic alterations and malignant transformation exists,although the effects of nutrients,primarily glucose,on the CSC behavior are still mostly *** is an essential fuel for cancer cells,and the connections with LDs in the healthy and CSC populations merit to be more deeply ***,we showed that a high glucose concentration activated the PI3K/AKT pathway and increased the expression of CD133 and CD44v6 CSC ***,glucose was responsible for the increased amount of Reactive Oxygen Species(ROS)and LDs in both healthy and CR-CSC *** also investigated the gene modulations following the HG treatment and found out that the healthy cell gene profile was the most ***,Atorvastatin,a lipidlowering drug,induced the highest mortality on CR-CSCs without affecting the healthy counterpart.

关键词： Cholesterol metabolism colorectal cancer stem cells Fatty acid

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