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Prognostic and predictive role of immune microenvironment in colorectal cancer

World Journal of Gastrointestinal Oncology 2024年第3期16卷 643-652页

作者： Olesya Kuznetsova Mikhail Fedyanin Larisa Zavalishina Larisa Moskvina Olga Kuznetsova Alexandra Lebedeva alexey tryakin.galin. kireeva Gleb Borshchev Sergei Tjulandin Ekaterina Ignatova Department of Chemotherapy Federal State Budgetary Institution(N.N.Blokhin National Medical Research Center of Oncology)of the Ministry of Health of the Russian FederationMoscow 115478Russia Department of Pathology Russian Medical Academy of Continuous Professional EducationMoscow 123242Russia OncoAtlas LCC Moscow 115478Russia Federal State Budgetary Institution“National Medical and Surgical Center named after N.I.Pirogov”of the Ministry of Health of the Russian Federation Moscow 105203Russia STOONCO:Science and Technology in Oncology Moscow 115478Russia

Colorectal cancer(CRC)represents a molecularly heterogeneous disease and one of the most frequent causes of cancer-related death *** traditional classification of CRC is based on pathomorphological and molecular character-istics of tumor cells(mucinous,ring-cell carcinomas,etc.),analysis of mechanisms of carcinogenesis involved(chromosomal instability,microsatellite instability,CpG island methylator phenotype)and mutational statuses of commonly altered genes(KRAS,NRAS,BRAF,APC,etc.),as well as expression signatures(CMS 1-4).It is also suggested that the tumor microenvironment is a key player in tumor progression and metastasis in *** to the latest data,the immune microenvironment can also be predictive of the response to immune checkpoint *** this review,we highlight how the immune environment influences CRC prognosis and sensitivity to systemic therapy.

关键词： Immunoscore Immune microenvironment Colorectal cancer Gastrointestinal cancers Predictive biomarkers Digital pathology

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Clinical significance of molecular subtypes of gastrointestinal tract adenocarcinoma

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World Journal of Gastrointestinal Oncology 2022年第3期14卷 628-645页

作者： Ekaterina Olegovna Ignatova Evgenii Kozlov Maxim Ivanov Vladislav Mileyko Sofia Menshikova Henian Sun Mikhail Fedyanin alexey tryakin Ivan Stilidi Department of Second Chemotherapy Federal State Budgetary Institution“N.N.Blokhin National Medical Research Center of Oncology”of the Ministry of Health of the Russian FederationMoscow 115478MoscowRussia Department of Oncogenetics Research Centre for Medical Genetics Research Centre for Medical GeneticsMoscow 115522MoscowRussia OncoAtlas LLC Moscow 121069MoscowRussia Department of Biological and Medical Physics Moscow Institute of Physics and TechnologyMoscow 141700MoscowRussia Department of Anticancer Drug Treatment AO K31 CityMoscow 121552MoscowRussia Pirogov Russian National Research Medical University(Pirogov Medical University) Moscow 117997MoscowRussia

Adenocarcinomas of the gastrointestinal tract(esophagus,stomach,and colon)represent a heterogeneous group of diseases with distinct etiology,clinical features,treatment approaches,and *** are ongoing to isolate molecular genetic subtypes,perform complete biological characterization of the tumor,determine prognostic groups,and find predictive markers to the effectiveness of *** molecular genetic classifications were created for esophageal adenocarcinoma[The Cancer Genome Atlas(TCGA)],stomach cancer(TCGA,Asian Cancer Research Group),and colon cancer(Colorectal Cancer Subtyping Consortium).In 2018,isolation of TCGA molecular genetic subtypes for adenocarcinomas of the gastrointestinal tract(esophagus,stomach,and colon)highlighted the need for further studies and clinical validation of subtyping of gastrointestinal ***,this approach has *** aim of our work was to critically analyze integration of molecular genetic subtyping of gastrointestinal adenocarcinomas in clinical practice.

关键词： Esophageal adenocarcinoma Gastric cancer Colon cancer Gene sequencing,Gene expression profiling Molecular subtypes

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Second-line treatment of metastatic gastric cancer:Current options and future directions

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World Journal of Gastroenterology 2015年第41期21卷 11621-11635页

作者： Dheepak Kanagavel Mikhail Fedyanin alexey tryakin Sergei Tjulandin Department of Clinical Pharmacology andChemotherapy N. N. Blokhin Russian Cancer Research Center

Gastric cancer remains one among the leading causes of cancer-related deaths, regardless of its decreasing incidence and newly available treatment options. Most patients present at an advanced stage and are treated with upfront systemic chemotherapy. Those patients receiving first-line therapy may initially respond to treatment, but many of them relapse over time. In such condition, second-line treatment for disease progression remains the only available option. Although there exists no standard approach in the second-line setting, several phase Ⅲ trials have shown modest survival benefit in patients receiving irinotecan, taxane and ramucirumab over the best supportive care or active agents. This review analyzes the currently available treatment regimens and future directions of research in the second-line setting for metastatic gastric cancer with the best available evidence. Additionally, the prognostic factors that influence patient survival in those receiving second-line therapy are discussed.

关键词： Metastatic gastric cancer Second-line chemotherapy

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Conversion of Unresectable to Resectable Liver Metastases from Colorectal Carcinoma Using Hepatic Arterial Chronomodulated Chemotherapy: A Case Report and Short Literature Review

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Surgical Science 2018年第10期9卷 358-366页

作者： Evgeny Y. Parnes Maria S. Sayapina alexey A. tryakin Mohamed Bouchahda Pasquale F. Innominato Jean-Francois Morere Francis A. Levi Rene Adam The Central Clinical Hospital of Civil Aviation Moscow Russia N.N. Blokhin Russian Oncology Research Center Moscow Russia Department of Medical Oncology Assistance Publique H&ocirc pitaux de Paris H&ocirc pital Paul Brousse Villejuif France INSERM UMRS 776 “Biological Rhythms and Cancers” Campus CNRS Villejuif France Cancer Chronotherapy Team Warwick Medical School Coventry United Kingdom Hepato-Biliary Center Assistance Publique H&ocirc pitaux de Paris H&ocirc pital Paul Brousse Villejuif France

Background: The regional chronomodulated hepatic arterial infusion chemotherapy (HAIC) is an effective regimen for the treatment of patients with unresectable liver metastases from colorectal cancer, especially for the conversion into resectability. Aim: To demonstrate that chronomodulated HAI triplet chemotherapy according to OPTILIV protocol is well tolerated and displayed high antitumor activity in this heavily-pretreated patient. Case Presentation: A 54 years old patient from Russia was treated for a tumor in the ascending colon presented with 13 hepatic metastases ranging from 0.3 to 2.7 cm in diameter. He underwent a laparoscopic right hemicolectomy, 12 cycles of FOLFIRINOX combined to bevacizumab for the last 5 cycles, resulting in a partial response according to CT scan. It was decided to perform a two-stage hepatectomy at Paul Brousse hospital: left partial hepatectomy allowed the excision of 9 lesions. Radio frequency ablation was performed in 2 nodular lesions. Afterwards, the patient received 5 cycles of chronomodulated triplet chemotherapy into the hepatic artery, according to the OPTILIV protocol design, yet without cetuximab, because of the KRAS mutation in the liver metastases, with a partial re-sponse. The patient could then undergo the second stage of the planned right hepatectomy, which turned out to be an R0 resection followed by receiving three courses of chronomodulated HAIC. Disease progression was documented after 3 months. Chronomodulated FOLFIRI chemotherapy was re-started intravenously, in combination with Aflibercept and it was associated with further disease progression. The genetic analysis of our patient’s cancer revealed a high level of MSI. The patient was included in the Phase 2 CheckMate-142 trial and received nivolumab 3 mg/kg every 2 weeks within 3 months. Treatment was discontinued due to ineffectiveness. Then the patient underwent radiotherapy geared towards reduction of pain. Afterwards, the patient died from the disease progr

关键词： The Regional Chronomodulated Hepatic Arterial Infusion Chemotherapy Metastatic Colorectal Cancer Conversion of Unresectable to Resectable Liver Metastases

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