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No association of the cytotoxic t-lymphocyte associated gene CtLA4 +49A/G polymorphisms with Crohn's disease and ulcerative colitis in Hungarian population samples

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World Journal of Gastroenterology 2007年第15期13卷 2205-2208页

作者： Lili Magyari Bernadett Faragó Judit Bene Katalin Horvatovich Lilla Lakner Márta Varga Mária Figler Beáta Gasztonyi Gyula Mózsik Béla Melegh Department of Medical Genetics and Child Development University of Pécs PécsHungary MtA PtE Clinical Genetics Research Group of the Hungarian Academy of Sciences at the University of Pécs Pécs Hungary Markusovszky Hospital Department of Medicine and Gastroenterology SzombathelyHungary Réthy Pál Hospital 3rd Department of Medicine and Gastroenterology BékéscsabaHungary Department of Medicine School of Medicine University of PécsPécsHungary Department of Gastroenterology Zala County Hospital ZalaegerszegHungary

AIM： the goal of the current work was to analyse the prevalence of the ＋49A/G variant of the cytotoxic t-lymphocyte antigen 4 gene （CtLA4） in Hungarian patients with Crohn＇s disease （CD） and ulcerative colitis （UC）. MEtHODS： A total of 130 unrelated subjects with CD and 150 with UC, and 170 matched controls were genotyped for the single nucleotide polymorphism （SNP）. the genotypes were determined by using PCR/RFLP test. RESULtS： the G allele frequency and the prevalence of the GG genotype were 38.1% and 12.3% in the CD group, 40.6% and 18.6% in the UC patients, and 37.4% and 15.9% in the control group, respectively. CONCLUSION： the results of the current study show that carriage of the ＋49G SNP in heterozygous or in homozygous form does not confer risk either for CD or for UC in the Hungarian population.

关键词： cytotoxic t-lymphocyte antigen 4 Crohn's disease Ulcerative colitis Inflammatory bowel disease

Immune checkpoint inhibitor-mediated colitis in gastrointestinal malignancies and inflammatory bowel disease

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World Journal of Gastrointestinal Oncology 2021年第8期13卷 772-798页

作者： Alexa R Weingarden Samuel J S Rubin John Gubatan Division of Gastroenterology and Hepatology Department of MedicineStanford UniversityRedwood CityCA 94063United States Stanford University School of Medicine Stanford UniversityRedwood CityCA 94063United States

Immune checkpoint inhibitors(ICI)have markedly changed the landscape of cancer *** re-invigorating the immune system against tumors,ICI provide novel therapeutic options for a broad variety of malignancies,including many gastrointestinal(GI)***,these therapies can also induce autoimmune-like side effects in healthy tissue across the *** of the most common of these side effects is ICI-mediated colitis and diarrhea(IMC).Here,we review the incidence and risk of IMC in ICI therapy,with a focus on what is known regarding IMC in patients with GI *** also discuss data available on the use of ICI and risk of IMC in patients with pre-existing inflammatory bowel disease,as these patients may have increased risk of IMC due to their underlying intestinal pathology.

关键词： Immune checkpoint inhibitors cytotoxic t-lymphocyte antigen 4 Programmed cell death protein-1 Inflammatory bowel disease Gastrointestinal cancer

Clinical characteristics of gastrointestinal immune-related adverse events of immune checkpoint inhibitors and their association with survival

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World Journal of Gastroenterology 2021年第41期27卷 7190-7206页

作者： Kentaro Yamada tsunaki Sawada Masanao Nakamura takeshi Yamamura Keiko Maeda Eri Ishikawa tadashi Iida Yasuyuki Mizutani Naomi Kakushima takuya Ishikawa Kazuhiro Furukawa Eizaburo Ohno takashi Honda Hiroki Kawashima Masatoshi Ishigami Satoshi Furune tetsunari Hase Kenji Yokota Osamu Maeda Naozumi Hashimoto Masashi Akiyama Yuichi Ando Mitsuhiro Fujishiro Department of Gastroenterology and Hepatology Nagoya University Graduate School of MedicineNagoya City 4668560AichiJapan Department of Endoscopy Nagoya University HospitalNagoya City 4668560AichiJapan Department of Clinical Oncology and Chemotherapy Nagoya University HospitalNagoya City 4668560AichiJapan Department of Respiratory Medicine Nagoya University Graduate School of MedicineNagoya City 4668560AichiJapan Department of Dermatology Nagoya University Graduate School of MedicineNagoya City 4668560AichiJapan Department of Gastroenterology and Hepatology Graduate School of MedicineThe University of TokyoTokyo 1138655Japan

BACKGROUND Despite the popularity of immune checkpoint inhibitors(ICIs)in the treatment of advanced cancer,patients often develop gastrointestinal(GI)and non-GI immune-related adverse events(irAEs).the clinical characteristics and survival outcomes of GI-irAEs have not been fully elucidated in previous *** necessitates the evaluation of the impact of GI-irAEs on patients receiving ICI *** to evaluate the clinical characteristics of GI-irAEs and their impact on survival in patients treated with *** In this single-center,retrospective,observational study,we reviewed the records of 661 patients who received ICIs for various cancers at Nagoya University Hospital from September 2014 to August *** analyzed the clinical characteristics of patients who received ICI *** also evaluated the correlation between GI-irAE development and prognosis in non-small cell lung cancer(LC)and malignant melanoma(MM).Kaplan-Meier analysis was used to compare the median overall survival(OS).Multivariate Cox proportional hazards models were used to identify prognostic factors.A P valuetatistically *** GI-irAEs occurred in 34 of 605 patients(5.6%)treated with an anti-programmed cell death-1/programmed death-ligand 1(anti-PD-1/PD-L1)antibody alone and in nine of 56 patients(16.1%)treated with an anti-cytotoxic t-lymphocyte antigen 4(CtLA-4)antibody alone or a combination of anti-PD-1 and anti-CtLA-4 *** cumulative incidence and median daily diarrhea frequency were significantly higher in patients receiving anti-CtLA-4 antibodies(Ptients with MM,OS was significantly prolonged in the group that continued ICI treatment despite the development of GI-irAEs compared to the group that did not experience GI-irAEs(P=0.035).In contrast,in 209 patients with non-small cell LC,there was no significant difference in OS between the *** multivariate analyses showed that a performance status of 2-3(ha

关键词： Colitis cytotoxic t-lymphocyte antigen 4 Diarrhea Drug-related side effects and adverse reactions Immune checkpoint inhibitors Prognosis

Drug resistance in cancer immunotherapy:new strategies to improve checkpoint inhibitor therapies

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Cancer Drug Resistance 2019年第4期2卷 980-993页

作者： Jesus Rodriguez-Pascual Angel Ayuso-Sacido Cristobal Belda-Iniesta Department of Clinical Oncology HM-CIOCCGrupo HM HospitalesMadrid 28050Spain Fundación de Investigación HM Hospitales(FiHM) Madrid 28015Spain Instituto de Salud Carlos III Madrid 28029Spain

Recent advances in pharmacological immune modulation against tumor cells has dramatically changed the paradigm of cancer *** inhibitor therapy is a form of cancer immunotherapy already in clinical setting but also under active basic and clinical ***,some patients are primary unresponsive or develop ulterior resistance to these family of *** review aims to update the basic molecular mechanism of resistance as well as the current strategies for checkpoint inhibitor selection in order to propose new approaches to individualize the use of these novel therapies.

关键词： Immunotherapy checkpoint inhibitors cytotoxic t-lymphocyte antigen 4 programmed death receptor-1 programmed death ligand-1

Common endocrine system adverse events associated with immune checkpoint inhibitors

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Cancer Pathogenesis and therapy 2024年第3期2卷 164-172页

作者： Ying Li Junfeng Zhao Yue Wang Yali Xu Ruyue Li Ying Zhao Xue Dong Xiujing Yao Yintao Li Department of Medical Oncology Shandong Cancer Hospital and InstituteShandong First Medical UniversityShandong Academy of Medical SciencesJinanShandong 250000China Department of Radiation Oncology Shandong Cancer Hospital and InstituteShandong First Medical UniversityShandong Academy of Medical SciencesJinanShandong 250000China National Institutes for Food and Drug Control Beijing 102629China Department of Pathology Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinanShandong 250000China Department of Medical Oncology Shandong Cancer Hospital and InstituteAffiliated Hospital of Weifang Medical UniversitySchool of Clinical MedicineWeifang Medical UniversityWeifangShandong 261000China

Immune checkpoint inhibitors(ICIs),a novel anti-tumor therapeutic modality,are monoclonal antibodies targeting certain immune checkpoints(ICs)that reactivate t cells to achieve anti-tumor immunity by targeting,binding,and blocking *** inhibitory antibodies against the ICs cytotoxic t-lymphocyte antigen and programmed death receptor-1 have demonstrated efficacy and durable anti-tumor activity in patients with *** may prevent autoimmune ***,ICIs may disrupt ICs properties and trigger autoimmune-related adverse reactions involving various organ systems including the cardiovascular,pulmonary,gastrointestinal,renal,musculoskeletal,dermal,and endocrine *** 10%of patients with damage to target organs such as the thyroid,pituitary,pancreas,and adrenal glands develop endocrine system immune-related adverse events(irAEs)such as thyroid dysfunction,pituitary gland inflammation,diabetes mellitus,and primary adrenal ***,the symptoms of immunotherapy-associated endocrine system irAEs may be nonspecific and similar to those of other treatment-related adverse reactions,and failure to recognize them early may lead to *** detection and treatment of immunotherapy-associated endocrine irAEs is essential to improve the efficacy of immunotherapy,prognosis,and the quality of life of *** study aimed to review the mechanisms by which ICIs cause endocrine irAEs providing guidance for the development of appropriate management ***,we discuss(1)the biological mechanisms of ICs in tumorigenesis and progression,focusing on cytotoxic t-lymphocyte antigen and programmed cell death-1/programmed cell death-ligand 1;and(2)the epidemiology,clinical symptoms,diagnosis,and treatment of four immunotherapy-related endocrine complications.

关键词： Immune checkpoint inhibitors Immune checkpoints cytotoxic t-lymphocyte antigen 4 Programmed cell death-1 Programmed cell death-ligand 1 Endocrine autoimmune-related adverse reactions