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Impact of oxaliplatin and trastuzumab combination therapy on tumor markers and T lymphocyte subsets for advanced gastric cancer

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World Journal of Gastrointestinal Oncology 2024年第9期16卷 3905-3912页

作者： Cheng-Wan Zheng Yun-Mo Yang Hui Yang Department of Thyroid Surgery The Affiliated Hospital of Southwest Medical UniversityLuzhou 646000Sichuan ProvinceChina

BACKGROUND Advanced gastric cancer(AGC)remains a challenging malignancy with poor *** combination of oxaliplatin and trastuzumab has shown promising results in AGC *** study aimed to investigate the effects of oxaliplatin and trastuzumab combination therapy on serum tumor markers and T lymphocyte subsets in patients with AGC and to explore their potential as predictive biomarkers for treatment *** To investigate the impact of oxaliplatin and trastuzumab combination therapy on serum markers and T cell subsets in patients with *** This prospective study enrolled 60 patients with *** patients received oxaliplatin(130 mg/m^(2),every 3 weeks)and trastuzumab(8 mg/kg loading dose,followed by 6 mg/kg every 3 weeks)for six *** carcinoembryonic antigen(CEA),cancer antigen 19-9(CA19-9),and cancer antigen 72-4(CA72-4)were measured before and after treatment.T-lymphocyte subsets,including CD3+,CD4+,CD8+,and CD4+/CD8+ratios,were also *** clinical response was assessed using the Response Evaluation Criteria in Solid Tumors version *** After six cycles of treatment,the CEA,CA19-9,and CA72-4 serum levels significantly decreased compared to baseline levels(Ppredictive biomarkers for treatment respon

关键词： Advanced gastric cancer Oxaliplatin Trastuzumab Serum tumor markers T lymphocyte subsets predictive biomarkers

Molecular predictive markers in tumors of the gastrointestinal tract

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World Journal of Gastrointestinal Oncology 2016年第11期8卷 772-785页

作者： Eirini Papadopoulou Vasiliki Metaxa-Mariatou Georgios Tsaousis Nikolaos Tsoulos Angeliki Tsirigoti Chrisoula Efstathiadou Angela Apessos Konstantinos Agiannitopoulos Georgia Pepe Eugenia Bourkoula George Nasioulas Department of Molecular Biology Gene Kor Medical S.A.

Gastrointestinal malignancies are among the leading causes of cancer-related deaths worldwide. Like all human malignancies they are characterized by accumulation of mutations which lead to inactivation of tumor suppressor genes or activation of oncogenes. Advances in Molecular Biology techniques have allowed for more accurate analysis of tumors’ genetic profiling using new breakthrough technologies such as next generation sequencing (NGS), leading to the development of targeted therapeutical approaches based upon biomarker-selection. During the last 10 years tremendous advances in the development of targeted therapies for patients with advanced cancer have been made, thus various targeted agents, associated with predictive biomarkers, have been developed or are in development for the treatment of patients with gastrointestinal cancer patients. This review summarizes the advances in the field of molecular biomarkers in tumors of the gastrointestinal tract, with focus on the available NGS platforms that enable comprehensive tumor molecular profile analysis.

关键词： predictive biomarkers Targeted therapy Next generation sequencing Gastrointestinal tract Somatic mutations Liquid biopsy

Emerging predictors of the response to the blockade of immune checkpoints in cancer therapy

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Cellular & Molecular Immunology 2019年第1期16卷 28-39页

作者： Xiaolei Li Wenhui Song Changshun Shao Yufang Shi Weidong Han The First Affiliated Hospital of Soochow University and State Key Laboratory of Radiation Medicine and Radioprotection Institutes for Translational MedicineSoochow UniversitySuzhouJiangsu 215123China Department of Molecular Biology Immunology and Bio-therapeuticInstitute of Basic MedicineChinese PLA General HospitalBeijing 100853China The Second Hospital of Shanxi Medical University TaiyuanShanxi 030001China

Checkpoint blockade-based immunotherapy offers new options and powerful weapons for the treatment of cancer,but its efficacy varies greatly among different types of cancer and across individual ***,the development of the right tools that can be used to identify patients who could benefit from this therapy is of utmost importance in order to maximize the therapeutic benefit,minimize risk of toxicities,and guide combination *** predictors have emerged that are based on checkpoint receptor ligand expression,tumor mutational burden,neoantigen and microsatellite instability,tumor-infiltrating immune cells,and peripheral blood *** this review,we discuss the current state and progress of predictors as aids in checkpoint blockadebased immunotherapy in cancer.

关键词： Cancer immunotherapy Checkpoint blockade immunotherapy predictive biomarkers Precision oncology

Exploitation of Gene Expression and Cancer biomarkers in Paving the Path to Era of Personalized Medicine

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Genomics, Proteomics & Bioinformatics 2017年第4期15卷 220-235页

作者： Hala Fawzy Mohamed Kamel Hiba Saeed A.Bagader Al-Amodi Biochemistry Department Faculty of Medicine Umm AL-Qura University Medical Biochemistry Department Faculty of Medicine Ain Shams University

Cancer therapy agents have been used extensively as cytotoxic drugs against tissue or organ of a specific type of cancer. With the better understanding of molecular mcchanislns undcrlying carcinogenesis and cellular events during cancer progression and metastasis, it is now possible to use targeted therapy for these molecular events. Targeted therapy is able to identify cancer patients with dissimilar genetic defects at cellular level for the same cancer type and consequently requires individualized approach for treatment. Cancer therapy begins to shill steadily from the tra- ditional approach of ＂one regimen for all patients＂ to a more individualized approach, through which each patient will be treated specifically according to their specific genetic defects. Personalized medicine accordingly requires identification of indicators or markers that guide in the decision mak- ing of such therapy to the chosen patients for more effective therapy. Cancer biomarkcrs are fre- quently used in clinical practice for diagnosis and prognosis, as well as identification ol responsive patients and prediction of treatment response of cancer patient. The rapid breakthrough and development of microarray and sequencing technologies is probably the main tool for paving the way toward ＂individualized biomarker-driven cancer therapy＂ or ＂personalized medicine＂. In this review, we aim to provide an updated knowledge and overview of the currcnt landscape of cancer biomarkers and their role in personalized medicine, emphasizing the impact of gcnomics Oil the implementation of new potential targeted therapies and development of novel cancer biomarkers in improving the outcome of cancer therapy.

关键词： Personalized medicine Gene expression Targeted therapy predictive biomarkers Prognostic biomarkers

Recent advances in immunotherapy for hepatocellular carcinoma

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Hepatobiliary & Pancreatic Diseases International 2021年第6期20卷 511-520页

作者： Abid Ali Khan Zhi-Kun Liu Xiao Xu Division of Hepatobiliary and Pancreatic Surgery Department of SurgeryThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Key Lab of Combined Multi-Organ Transplantation Collaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesMinistry of Public HealthHangzhou 310003China Department of Hepatobiliary and Pancreatic Surgery Affiliated Hangzhou First People's HospitalZhejiang University School of MedicineHangzhou 310006China

Background:Treatment of hepatocellular carcinoma(HCC)is challenging as most patients are diagnosed at advanced stage with underlying chronic liver *** systemic chemotherapy has failed in HCC,and the clinical efficacy of FDA-approved molecular targeted agents such as sorafenib and lenvatinib remains *** sources:Literature search was conducted in Pub Med for relevant articles published before January *** search aimed to identify recent developments in immune-based treatment approaches for *** of clinical trials was obtained from https://***/.Results:Two immune checkpoint inhibitors(ICIs),nivolumab and pembrolizumab were approved as monotherapies,which has revolutionized HCC ***,combination ICIs have also got accelerated FDA approval ***-based therapies have challenged targeted drugs owing to their safety,tolerability,and survival *** addition to the significant success in ICIs,other immunotherapeutic strategies such as cancer vaccine,chimeric antigen receptor T-cells,natural killer cells,cytokines,and combination therapy,have also shown promising outcomes in clinical *** diagnostic and prognostic biomarkers have been identified which can help in clinical decision making when starting treatment with ***:Immunotherapy has emerged as one of the mainstream treatment modalities for advanced HCC in recent ***,challenges such as low response rate and acquired resistance in previously respondent patients still *** research is needed to understand the unique resistance mechanism to immunotherapy and to discover more predictive biomarkers to guide clinical decision making.

关键词： Hepatocellular carcinoma Immunotherapy Immune checkpoint inhibitor Adoptive cellular therapy Immune evasion Combination therapy predictive biomarkers

Immunohistochemical evaluation of vitamin D receptor(VDR) expression in cutaneous melanoma tissues and four VDR gene polymorphisms

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Cancer Biology & Medicine 2017年第2期14卷 162-175页

作者： Francesco La Marra Giuseppe Stinco Cinzia Buligan Giovanni Chiriacò Diego Serraino Carla Di Loreto Sabina Cauci Department of Medical Area School of MedicineUniversity of Udine Dermatology Clinic Udine University-HospitalUniversity of Udine Unit of Cancer Epidemiology CRO Aviano National Cancer Institute

Objective:Vitamin D receptor(VDR)mediates vitamin D *** examined whether VDR expression in excised melanoma tissues is associated with VDR gene(VDR)***:We evaluated VDR protein expression(by monoclonal antibody immunostaining),melanoma characteristics,and carriage of VDR-Fok I-rs2228570(C>T),VDR-Bsm I-rs1544410(G>A),VDR-ApaI-rs7975232(T>G),and VDR-TaqI-rs731236(T>C)polymorphisms(by restriction fragment length polymorphism).Absence or presence of restriction site was denoted by a capital or lower letter,respectively:"F"and"f"for Fok I,"B"and"b"for Bsm I,"A"and"a"for ApaI,and "T"and"t"for TaqI ***-four Italian cutaneous primary melanomas(52.1±12.7 years old)were studied;51.4% were stage Ⅰ,21.6% stage Ⅱ ,13.5% stage Ⅲ,and 13.5% stage Ⅳ *** expression was categorized as follows:100% positive vs.1,regression,tumor-infiltrating lymphocytes,tumoral infiltration of vascular tissues,additional skin and non-skin cancers,and melanoma ***:We highlighted that VDR polymorphisms can affect VDR expression in excised melanoma *** VDR expression in AATT carriers is a new finding that merits further *** expression possibly poses implications for vitamin D supplementation against *** expression and VDR genotype may become precise medicinal tools for melanoma in the future.

关键词： Vitamin D receptor VDR protein expression VDR polymorphism cutaneous melanoma metastatic melanoma skin cancer predictive biomarkers FokI polymorphism

Transcriptomic biomarkers for predicting response to neoadjuvant treatment in oesophageal cancer

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Gastroenterology Report 2020年第6期8卷 411-424,I0001页

作者： Anita Lavery Richard C.Turkington Patrick G Johnston Centre for Cancer Research Queen’s University BelfastBelfastUK

Oesophageal cancer is a devastating disease with poor outcomes and is the sixth leading cause of cancer death *** the setting of resectable disease,there is clear evidence that neoadjuvant chemotherapy and chemoradiotherapy result in improved ***,only 15%-30%of patients obtain a histopathological response to neoadjuvant therapy,often at the expense of significant *** are no predictive biomarkers in routine clinical use in this setting and the ability to stratify patients for treatment could dramatically improve *** this review,we aim to outline current progress in evaluating predictive transcriptomic biomarkers for neoadjuvant therapy in oesophageal cancer and discuss the challenges facing biomarker development in this *** place these issues in the wider context of recommendations for biomarker development and *** majority of studies focus on messenger RNA(mRNA)and microRNA(miRNA)*** studies report a range of different genes involved in a wide variety of pathways and biological processes,and this is explained to a large extent by the different platforms and analysis methods *** studies are also vastly underpowered so are not suitable for identifying a candidate *** molecular subtypes of oesophageal cancer have been proposed,although little is known about how these relate to clinical *** anticipate that the accumulating wealth of genomic and transcriptomic data and clinical trial collaborations in the coming years will provide unique opportunities to stratify patients in this poor-prognosis disease and recommend that future biomarker development incorporates well-designed retrospective and prospective analyses.

关键词： oesophageal cancer predictive biomarkers chemotherapy radiotherapy gene expression pathological response

Laboratory scoring system to predict hepatic indocyanine green clearance ability during fluorescence imaging-guided laparoscopic hepatectomy

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World Journal of Gastrointestinal Surgery 2023年第7期15卷 1442-1453页

作者： Zhen-Rong Chen Qing-Teng Zeng Ning Shi Hong-Wei Han Zhi-Hong Chen Yi-Ping Zou Yuan-Peng Zhang Fan Wu Lian-Qun Xu Hao-Sheng Jin Guangdong Cardiovascular Institute Guangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesGuangzhou 510000Guangdong ProvinceChina Department of General Surgery Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhou 510000Guangdong ProvinceChina Department of Hepatobiliary Surgery Shenzhen Hospital of Traditional Chinese MedicineShenzhen 518000Guangdong ProvinceChina Medical College Shantou UniversityShantou 515000Guangdong ProvinceChina

BACKGROUND Indocyanine green(ICG)fluorescence played an important role in tumor localization and margin delineation in hepatobiliary ***,the preoperative regimen of ICG administration was still *** associated with tumor fluorescence staining effect were *** To investigate the preoperative laboratory indexes corelated with ICG fluorescence staining effect and establish a novel laboratory scoring system to screen specifical patients who need ICG dose *** To investigate the predictive indicators of ICG fluorescence characteristics in patients undergoing laparoscopic hepatectomy from January 2018 to January 2021 were *** laboratory tests were completed within 1 wk before *** patients received 5 mg ICG injection 24 h before surgery for preliminary tumor *** software was used to measure the fluorescence intensity values of regions of *** analysis was used to identify risk factors.A laboratory risk model was established to identify individuals at high risk for high liver background *** There were 110 patients who were enrolled in this study from January 2019 to January *** mean values of fluorescence intensity of liver background(FI-LB),fluorescence intensity of gallbladder,and fluorescence intensity of target area were 18.87±17.06,54.84±33.29,and 68.56±36.11,*** receiver operating characteristic(ROC)curve showed that FI-LB was a good indicator for liver clearance ability[area under the ROC curve(AUC)=0.984].Correlation analysis found pre-operative aspartate aminotransferase,alanine aminotransferase,gammaglutamyl transpeptidase,adenosine deaminase,and lactate dehydrogenase were positively associated with FI-LB and red blood cell,cholinesterase,and were negatively associated with *** laboratory risk score(TLRS)was calculated according to ROC curve(AUC=0.848,sensitivity=0.773,specificity=0.885).When TLRS was greater than 6.5,the liver

关键词： Indocyanine green Fluorescence Laparoscopic Hepatectomy predictive biomarkers Blood index

biomarkers of resistance to immune checkpoint inhibitors in non-small-cell lung cancer:myth or reality?

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Cancer Drug Resistance 2020年第3期3卷 276-286页

作者： Ivan Pourmir Benoit Gazeau Hortense de Saint Basile Elizabeth Fabre Department of Thoracic oncology Hôpital européen Georges PompidouParis 75015France. INSERM U970 UniversitéParis Descartes Sorbonne Paris-CitéParis 75015France.

Immune checkpoint inhibitors represent a major therapeutic advance in non-small-cell lung cancer with several approved anti-programmed death-1 and anti-programmed death-L1 immunotherapies.A majority of patients however,will not respond to immune checkpoint inhibitors and display primary resistance while a subset of initially responsive patients will present secondary ***,there is a crucial need for biomarkers to enable better prediction and diagnosis,and to overcome such *** with improvement in the understanding of immune escape,new biomarkers are being developed,including large scale proteomic,genomic and transcriptomic approaches in tumor and blood *** review the novel biomarkers that have been investigated in non-small-cell lung cancer and discuss how they can rationalize therapeutic strategies.

关键词： Non-small-cell lung cancer immune checkpoint inhibitors resistance predictive biomarkers diagnostic biomarkers programmed death ligand-1 tumor mutational burden circulating tumor DNA