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Clinicopathological significance and immunotherapeutic outcome of claudin 18.2 expression in advanced gastric cancer:A retrospective study

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Chinese Journal of Cancer Research 2024年第1期36卷 78-89页

作者： Changsong Qi Xiaoyi Chong Ting Zhou Mingyang Ma Jifang Gong Miao Zhang Jian Li Jun Xiao Xiaohui Peng Zhen Liu Zonghai Li Lin Shen Xiaotian Zhang State Key Laboratory of Holistic Integrative Management of gastrointestinal Cancers Beijing Key Laboratory of Carcinogenesis and Translational ResearchDepartment of Gastrointestinal OncologyPeking University Cancer Hospital&InstituteBeijing 100142China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department of Gastrointestinal OncologyPeking University Cancer Hospital&InstituteBeijing 100142China CARsgen therapeutics Co. LtdShanghai 200231China CARsgen Life Sciences Co. LtdShanghai 200131China

Objective: Immunotherapeutic outcomes and clinical characteristics of claudin 18 isoform 2 positive(CLDN18.2-positive) gastric cancer(GC) vary in different clinical studies, making it difficult to optimize antiCLDN18.2 therapy. We conducted a retrospective analysis to explore the association of CLDN18.2 expression with clinicopathological characteristics and immunotherapeutic outcomes in ***: A total of 536 advanced GC patients from 2019 to 2021 in the CT041-CG4006 and CT041-ST-01clinical trials were included in the analysis. CLDN18.2 expression on ≥40% of tumor cells(2+, 40%) and CLDN18.2 expression on ≥70% of tumor cells(2+, 70%) were considered the two levels of positively expressed GC. The clinicopathological characteristics and immunotherapy outcomes of GC patients were analyzed according to CLDN18.2 expression ***: CLDN18.2 was expressed in 57.6%(cut-off: 2+, 40%) and 48.9%(cut-off: 2+, 70%) of *** death-ligand 1(PD-L1) and CLDN18.2 were co-expressed in 19.8% [combined positive score(CPS)≥1, CLDN18.2(cut-off: 2+, 40%)] and 17.2% [CPS≥5, CLDN18.2(cut-off: 2+, 70%)] of ***18.2 expression positively correlated with younger age, female sex, non-gastroesophageal junction(nonGEJ), and diffuse phenotype(P<0.001). HER2 and PD-L1 expression were significantly lower in CLDN18.2-positive GC(both P<0.05). Uterine adnexa metastasis(P<0.001) was more frequent and liver metastasis(P<0.001)was less common in CLDN18.2-positive GC. Overall survival and immunotherapy-related progression-free survival(ir PFS) were inferior in the CLDN18.2-positive ***: CLDN18.2-positive GC is associated with poor prognosis and worse immunotherapeutic outcomes. The combination of anti-CLDN18.2 therapy, anti-PD-L1/PD-1 therapy, and chemotherapy for GC requires further investigation.

关键词： Gastric cancer claudin18.2 CT041 PD-L1 immunotherapy

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Anti-EGFR antibody monotherapy for colorectal cancer with severe hyperbilirubinemia: A case report

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World Journal of gastrointestinal Oncology 2024年第2期16卷 557-562页

作者： Toshiaki Tsurui Yuya Hirasawa Yutaro Kubota Kiyoshi Yoshimura Takuya Tsunoda Department of Medical Oncology Showa UniversityTokyo 1428555Japan Department of Clinical Immuno Oncology Clinical Research Institute of Clinical Pharmacology and TherapeuticsShowa UniversityTokyo 1578577Japan

BACKGROUND Hyperbilirubinemia with hepatic metastases is a common complication and a poor prognostic factor for colorectal cancer(CRC).Effective drainage is often im-possible before initiating systemic chemotherapy,owing to the liver’s diffuse metastatic ***,an appropriate chemotherapeutic approach for the treatment of hyperbilirubinemia is currently *** SUMMARY The patient,a man in his 50s,presented with progressive fatigue and severe *** tomography revealed multiple hepatic masses with thick-ened walls in the sigmoid colon,which was pathologically confirmed as a well-differentiated *** RAS or BRAF mutations were *** Eastern Cooperative Oncology Group(ECOG)performance status(PS)score was *** drainage was impossible due to the absence of a dilated bile duct,and panitumumab monotherapy was promptly ***,the bilirubin level decreased and then normalized,and the patient’s PS improved to zero ECOG score after four cycles of therapy without significant adverse *** Anti-EGFR antibody monotherapy is a safe and effective treatment for RAS wild-type CRC and hepatic metastases with severe hyperbilirubinemia.

关键词： Colorectal neoplasms Panitumumab Chemotherapy Hyperbilirubinemia Jaundice Case report

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The role of EPH receptors in cancer-related epithelial-mesenchymal transition

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Chinese Journal of Cancer 2014年第5期33卷 231-240页

作者： Rui-Xin Li Zi-Hua Chen Zhi-Kang Chen Department of gastrointestinal Surgery Xiangya HospitalCentral South University

Erythropoietin-producing hepatoma(EPH) receptors are considered the largest family of receptor tyrosine kinases and play key roles in physiological and pathologic processes in development and *** receptors are often overexpressed in human malignancies and are associated with poor ***,the functions of EPH receptors in epithelial-mesenchymal transition(EMT) remain largely *** review depicts the relationship between EPH receptors and the EMT marker E-cadherin as well as the crosstalk between EPH receptors and the signaling pathways involved *** discussion is focused on the clinical significance of EPH receptors as candidates for targeting in cancer ***,we summarize how targeted inhibition of both EPH receptors and EMT-related signaling pathways represents a novel strategy for cancer treatment.

关键词：受体酪氨酸激酶恶性肿瘤上皮转化间质促红细胞生成素信号通路癌症治疗

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Dieulafoy's lesion:A case series study

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World Journal of Gastroenterology 2005年第23期11卷 3574-3577页

作者： RS Walmsley Yuk-Tong Lee Joseph JY Sung Department of Gastroenterology Department of Medicine and therapeutics

AIM: Dieulafoy's lesion (DL) accounts for 1-5.8% of cases of acute upper gastrointestinal bleeding (GIB). Its mortality is high, approaching 20%, despite recent advances in endoscopic therapy. We aimed to report our experience in the treatment of ***: A retrospective case study of all patients with DL between January 1993 and January 2003 was done. Characteristics, treatment methods, success rates and 30-d mortality of the patients were analyzed. RESULTS: Thirty-six patients were noted to have DL in the study period. Thirty-three records were available for assessment in which 35 DL were identified. The median age of the patients was 67 years with male to female ratio of 5.6:1. Significant comorbidities existed in 69% of the patients. Eighty-nine percent of the DL was found at first endoscopy, three DL at laparotomy. Significant coexistent endoscopic findings existed in 23%. Hemostasis was achieved in 88% by using adrenaline injection, or in combination with heater probe application at first endoscopy. Four cases had re-bleeding, all were successfully treated endoscopically. The 30-d mortality rate was 23%.CONCLUSION: Successful endoscopic hemostasis could be achieved in 100% of cases of DL. The overall mortality may still remain high, mainly due to the comorbidities and age of these patients.

关键词： Dieulafoy gastrointestinal bleeding

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Dysbiosis promotes recurrence of adenomatous polyps in the distal colorectum

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World Journal of gastrointestinal Oncology 2024年第8期16卷 3600-3623页

作者： Li-Li Yin Ping-Qian Qi Yun-Fei Hu Xiao-Jun Fu Rui-Shan He Meng-Meng Wang Yan-Juan Deng Su-Yi Xiong Qi-Wen Yu Jin-Ping Hu Lv Zhou Zhi-Bin Zhou Ying Xiong Huan Deng The Affiliated Rehabilitation Hospital Jiangxi Medical CollegeNanchang UniversityNanchang 330006Jiangxi ProvinceChina The Fourth Affiliated Hospital Jiangxi Medical CollegeNanchang UniversityNanchang 330006Jiangxi ProvinceChina The Second College of Clinical Medicine Jiangxi Medical CollegeNanchang UniversityNanchang 330006Jiangxi ProvinceChina Tumor Immunology Institute Nanchang UniversityNanchang 330006Jiangxi ProvinceChina Department of General Medicine The Second College of Clinical MedicineJiangxi Medical CollegeNanchang UniversityNanchang 330031Jiangxi ProvinceChina The Ministry of Education Basic Research and Innovation Center for the Targeted therapeutics of Solid Tumors Jiangxi Medical CollegeNanchang UniversityNanchang 330031Jiangxi ProvinceChina

BACKGROUND Colorectal polyps,which are characterized by a high recurrence rate,represent preneoplastic conditions of the *** to unclear mechanisms of pathogenesis,first-line therapies for non-hereditary recurrent colorectal polyps are limited to endoscopic *** recent studies suggest a mechanistic link between intestinal dysbiosis and polyps,the exact compositions and roles of bacteria in the mucosa around the lesions,rather than feces,remain *** To clarify the composition and diversity of bacteria in the mucosa surrounding or 10 cm distal to recurrent intestinal *** Mucosal samples were collected from four patients consistently with adenomatous polyps(Ade),seven consistently with non-Ade(Pol),ten with current Pol but previous Ade,and six healthy individuals,and bacterial patterns were evaluated by 16S rDNA *** discriminant analysis and Student’s t-tests were used to identify the genus-level bacteria differences between groups with different colorectal polyp ***’s correlation coefficients were used to evaluate the correlation between intestinal bacteria at the genus level and clinical *** The results confirmed a decreased level of probiotics and an enrichment of pathogenic bacteria in patients with all types of polyps compared to healthy *** changes were not restricted to the mucosa within 0.5 cm adjacent to the polyps,but also existed in histologically normal tissue 10 cm distal from the *** differences in bacterial diversity were observed in the mucosa from individuals with normal conditions,Pol,and *** abundance of Gram-negative bacteria,including Klebsiella,Plesiomonas,and Cronobacter,was observed in Pol group and Ade group,suggesting that resistance to antibiotics may be one risk factor for bacterium-related harmful ***,age and gender were linked to bacteria changes,indicating the potential involvement of sex hormone

关键词： Dysbiosis Biopsy Polyp Bacteria Colorectum

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Extracellular vesicles:General features and usefulness in diagnosis and therapeutic management of colorectal cancer

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World Journal of gastrointestinal Oncology 2021年第11期13卷 1561-1598页

作者： Aurelien Mammes Jennifer Pasquier Olivier Mammes Marc Conti Richard Douard Sylvain Loric INSERM UMR-938 Cancer Biology and Therapeutics UnitSaint-Antoine Research CenterSaint Antoine University HospitalParis 75012France UCBM Necker University HospitalParis 75015France Metabolism Research Unit Integracell SASLongjumeau 91160France gastrointestinal Surgery Department Clinique BizetParis 75016France

In the world,among all type of cancers,colorectal cancer(CRC)is the third most commonly diagnosed in males and the second in *** most of cases,(RP1)patients’prognosis limitation with malignant tumors can be attributed to delayed diagnosis of the *** of patients with early-stage disease leads to more effective therapeutic ***,new screening methods and further innovative treatment approaches are mandatory as they may lead to an increase in progression-free and overall survival *** the last decade,the interest in extracellular vesicles(EVs)research has exponentially increased as EVs generation appears to be a universal feature of every cell that is strongly involved in many mechanisms of cell-cell communication either in physiological or pathological *** can cargo biomolecules,such as lipids,proteins,nucleic acids and generate transmission signal through the intercellular transfer of their *** this mechanism,tumor cells can recruit and modify the adjacent and systemic microenvironment to support further invasion and *** review intends to cover the most recent literature on the role of EVs production in colorectal normal and cancer *** attention is paid to the use of EVs for early CRC diagnosis,follow-up,and prognosis as EVs have come into the spotlight of research as a high potential source of‘liquid biopsies’.The use of EVs as new targets or nanovectors as drug delivery systems for CRC therapy is also summarized.

关键词： Extracellular vesicles Colorectal cancer Diagnostic Prognosis Vector Therapy

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Localization and role of metabotropic glutamate receptors subtype 5 in the gastrointestinal tract

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World Journal of Gastroenterology 2017年第25期23卷 4500-4507页

作者： Andrea Ferrigno Clarissa Berardo Laura G Di Pasqua Veronica Siciliano Plinio Richelmi Mariapia Vairetti Department of Internal Medicine and therapeutics (Cellular and Molecular Pharmacology and Toxicology) University of Pavia

Metabotropic glutamate receptor subtype 5 (mGluR5) is a Group I mGlu subfamily of receptors coupled to the inositol trisphosphate/diacylglycerol pathway. Like other mGluR subtypes, mGluR5s contain a phylogenetically conserved, extracellular orthosteric binding site and a more variable allosteric binding site, located on the heptahelical transmembrane domain. The mGluR5 receptor has proved to be a key pharmacological target in conditions affecting the central nervous system (CNS) but its presence outside the CNS underscores its potential role in pathologies affecting peripheral organs such as the gastrointestinal (GI) tract and accessory digestive organs such as the tongue, liver and pancreas. Following identification of mGluR5s in the mouth, various studies have subsequently demonstrated its involvement in mechanical allodynia, inflammation, pain and oral cancer. mGluR5 expression has also been identified in gastroesophageal vagal pathways. Indeed, experimental and human studies have demonstrated that mGluR5 blockade reduces transient lower sphincter relaxation and reflux episodes. In the intestine, mGluR5s have been shown to be involved in the control of intestinal inﬂammation, visceral pain and the epithelial barrier function. In the liver, mGluR5s have a permissive role in the onset of ischemic injury in rat and mice hepatocytes. Conversely, livers from mice treated with selective negative allosteric modulators and mGluR5 knockout mice are protected against ischemic injury. Similar results have been observed in experimental models of free-radical injury and in vivo mouse models of acetaminophen intoxication. Finally, mGluR5s in the pancreas are associated with insulin secretion control. The picture is, however, far from complete as the review attempts to establish in particular as regards identifying specific targets and innovative therapeutic approaches for the treatment of GI disorders.

关键词： Metabotropic glutamate receptor subtype 5 Esophagus Intestine Liver Pancreas

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One stomach,two subtypes of carcinoma—the differences between distal and proximal gastric cancer

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Gastroenterology Report 2021年第6期9卷 489-504页

作者： Yuan Zhang Peng-Shan Zhang Ze-Yin Rong Chen Huang Department of gastrointestinal Surgery Shanghai General HospitalShanghai Jiao Tong UniversityShanghaiP.R.China

Gastric cancer(GC)is one of the most common malignant tumors of the digestive tract,posing a significant risk to human *** the past 10 years,the pathological characteristics and the prognosis of GC have been determined based on the locations of the tumors that were then classified into two types—proximal and distal *** review focuses on the differences in epidemiology,etiology,cell source,pathological characteristics,gene expression,molecular markers,manifestations,treatment,prognosis,and prevention between proximal and distal GC to provide guidance and a basis for clinical diagnosis and treatment.

关键词： gastric cancer epidemiology pathology therapeutics prognosis

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MicroRNAs in biliary diseases

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World Journal of Gastroenterology 2012年第43期18卷 6189-6196页

作者： Patricia Munoz-Garrido Maite García-Fernández de Barrena Elizabeth Hijona Miguel Carracedo JoséJ G Marín Luis Bujanda Jesús M Banales Division of Hepatology and Gastroenterology Biodonostia Research InstituteDonostia Universitary Hospital20014 San SebastiánSpain Division of Oncology Research Schulze Center for Novel TherapeuticsMayo ClinicRochesterMN 55905United States Division of Hepatology and Gastroenterology Biodonostia Research InstituteDonostia Universitary Hospital20014 San SebastiánSpains Department of Liver and gastrointestinal Diseases National Institute for the Study of Liver and Gastrointestinal Diseases(CIBERehdfunded by the Spanish CarlosⅢInstitute)08036 BarcelonaSpain Department of Physiology and Pharmacology Experimental Hepatology and Drug Targeting(HEVEFARM)Biomedical Research Institute of Salamanca(IBSAL)University of Salamanca37008 SalamancaSpain Ikerbasque Basque Foundation for Science48011 BilbaoSpain

Cholangiopathies are a group of diseases primarily or secondarily affecting bile duct cells, and result in cholangiocyte proliferation, regression, and/or transformation. Their etiopathogenesis may be associated with a broad variety of causes of different nature, which includes genetic, neoplastic, immune-associated, infectious, vascular, and drug-induced alterations, or being idiopathic. miRNAs, small non-coding endogenous RNAs that post-transcriptionally regulate gene expres sion, have been associated with pathophysiological processes in different organs and cell types, and are postulated as potential targets for diagnosis and therapy. In the current manuscript, knowledge regarding the role of miRNAs in the development and/or progression of cholangiopathies has been reviewed and the most relevant findings in this promising field of hepatology have been highlighted.

关键词： miRNAs Cholangiopathies Cholangiocarcinoma Polycystic liver diseases Primary biliary cirrhosis

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Novel methylxanthine derivative-mediated anti-inflammatory effects in inflammatory bowel disease

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World Journal of Gastroenterology 2014年第5期20卷 1127-1138页

作者： In-Ah Lee Alan Kamba Daren Low Emiko Mizoguchi gastrointestinal Unit Department of Medicine Harvard Medical School Center for the Study of Inflammatory Bowel Disease Massachusetts General Hospital Harvard Medical School

Family 18 chitinases have a binding capacity with chitin, a polymer of N-acetylglucosamine. Recent studies strongly suggested that chitinase 3-like 1(CHI3L1, also known as YKL-40) and acidic mammalian chitinase, the two major members of family 18 chitinases, play a pivotal role in the pathogenesis of inflammatory bowel disease(IBD), bronchial asthma and several other inflammatory disorders. Based on the data from highthroughput screening, it has been found that three methylxanthine derivatives, caffeine, theophylline, and pentoxifylline, have competitive inhibitory effects against a fungal family 18 chitinase by specifically interacting with conserved tryptophans in the active site of this protein. Methylxanthine derivatives are also known as adenosine receptor antagonists, phosphodiesterase inhibitors and histone deacetylase inducers. Anti-in-flammatory effects of methylxanthine derivatives have been well-documented in the literature. For example, a beneficial link between coffee or caffeine consumption and type 2 diabetes as well as liver cirrhosis has been reported. Furthermore, theophylline has a long history of being used as a bronchodilator in asthma therapy, and pentoxifylline has an immuno-modulating effect for peripheral vascular disease. However, it is still largely unknown whether these methylxanthine derivativemediated anti-inflammatory effects are associated with the inhibition of CHI3L1-induced cytoplasmic signaling cascades in epithelial cells. In this review article we will examine the above possibility and summarize the biological significance of methylxanthine derivatives in intestinal epithelial cells. We hope that this study will provide a rationale for the development of methylxanthine derivatives, in particular caffeine,-based antiinflammatory therapeutics in the field of IBD and IBDassociated carcinogenesis.

关键词： Adherent-invasive Escherichia coli Chitinase 3-like 1 Chitinase inhibitors Intestinal epithelial cells Host-microbial interactions Inflammatory bowel disease

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