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Identification and characterization of mammaglobin-A epitope in heterogenous breast cancers for enhancing tumor-targeting therapy

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Signal Transduction and Targeted Therapy 2020年第1期5卷 1778-1788页

作者： Zhiqiang Liu Xiqin Yang Cuimi Duan Jiangxue Li Rongsheng Tong Yuting Fan Jiannan Feng Ruiyuan Cao Wu Zhong Xiaoyan Feng Heqiu Zhang Lulu Cai Beijing Institute of Basic Medical Sciences 27 Taiping RoadHaidian DistrictBeijing 100850China Personalized Drug Therapy Key Laboratory of Sichuan Province Department of PharmacySichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChengdu 611731China Beijing Institute of Pharmacology and Toxicology 27 Taiping RoadHaidian DistrictBeijing 100850China

Although targeted therapy has been extensively investigated for breast cancers,a molecular target with broad application is currently unavailable due to the high heterogeneity of these ***-A(Mam-A),which is overexpressed in most breast carcinomas,has been proposed as a promising ***,the lack of specific targeting moieties due to uncertain binding epitopes hampers further translational ***,seven potential epitopes of Mam-A were disclosed,and a unique epitope was then identified in most types of breast cancers,despite the genotypic *** phage display technology,the epitope was determined to be N-terminal amino acids 42–51 of Mam-A(N42–51).Then,the N42–51 epitope-specific monoclonal antibody,mAb785,was conjugated to poly lactic-co-glycolic acid(PLGA)nanoparticles loaded with therapeutic agents,thereby enhancing the drug uptake and therapeutic efficacy in different genotypes of breast *** computer simulation of the N42–51 epitope and the mAb785 structures,as well as their interactions,further revealed the specific targeting mechanism of the mAb785-conjugated nanoparticles to breast cancers.

关键词： breast cancers epitope

Colorectal cancers and chlorinated water

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World Journal of Gastrointestinal Oncology 2016年第4期8卷 402-409页

作者： Ahmed Mahmoud El-Tawil Department of Surgery University Hospital Birmingham

Published reports have revealed increased risk of colorectal cancers in people exposed to chlorinated drinking water or chemical derivatives of chlorination. Oestrogen plays a dual positive functions for diminishing the possibilities of such risk by reducing the entrance, and increasing the excretion, of these chemicals. In addition, there are supplementary measures that could be employed in order to reduce this risk further, such as boiling the drinking water, revising the standard concentrations of calcium, magnesium and iron in the public drinking water and prescribing oestrogen in susceptible individuals. Hypo-methylation of genomic DNA could be used as a biological marker for screening for the potential development of colorectal cancers.

关键词： Chlorinated drinking water Oestrogen Sex hormones Gender Colorectal cancers Trihalomethanes Carcinogenesis DNA hypo-methylation

OStme: Online consensus survival analysis web server for tumor microenvironment components of pan-cancers

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Genes & Diseases 2023年第6期10卷 2256-2259页

作者： Longxiang Xie Qiang Wang Xiaoyu Ma Guo Zhao Zhongyi Yan Huimin Li Wan Zhu Zhanjie Zuo Xiangqian Guo Department of Preventive Medicine Institute of Biomedical InformaticsBioinformatics CenterHenan Provincial Engineering Center for Tumor Molecular MedicineAcademy for Advanced Interdisciplinary StudiesSchool of SoftwareSchool of Basic Medical SciencesHenan UniversityKaifengHenan 475004China Department of Anesthesia Stanford UniversityStanfordCA 94305United States Thoracic Cancer Treatment Center Armed Police Beijing Corps HospitalBeijing 100027China

Tumor microenvironment(TME)is the environment around the tumor cells,consisting of extracellular matrix,nonmalignant stromal cells,and various types of immune cells(like macrophages,B and T lymphocytes).1 TME has been recurrently reported to play important roles in the progression of cancers.1 The mechanism study of TME may offer opportunities for targeted/immune ***,how TME components impact the prognosis of cancer patients remains to be determined.

关键词： cancers microenvironment prognosis

Checkpoint inhibitors in gastrointestinal cancers:Expectations and reality

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World Journal of Gastroenterology 2017年第17期23卷 3017-3021页

作者： Hampig Raphael Kourie Samer Tabchi Marwan Ghosn Department of Oncology Faculty of Medicine Saint Joseph University

Immune checkpoint inhibitors represent revolutionary anti-cancer agents, being rapidly approved in different malignancies and settings. Gastrointestinal(GI) cancers represent a wide variety of tumors with specific characteristics and different responses to various therapeutic alternatives; while some are chemosensitive others are chemo-resistant and only respond to more aggressive cytotoxic regimens, targeted therapies or a combination of both. Preliminary results of immune checkpoint inhibitors in some GI cancers are promising, namely in hepatocellular carcinoma, anal cancers and microsatellite instability high colorectal cancers. An impressive instead of a impressive number of immune checkpoint inhibitors are being evaluated in different indications in GI cancers as single agents or in combination with other agents. We reported in this paper ongoing and published trials evaluating immune checkpoint inhibitors in hepatocellular carcinoma and biliary tract cancers, esophageal, gastric, pancreatic, colorectal and anal cancers and we discussed the future perspectives of these agents in GI cancers.

关键词： Immunotherapies cancers Digestive Checkpoint inhibitors Gastrointestinal

Synchronous multiple primary gastrointestinal cancers with CDH1 mutations:A case report

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World Journal of Clinical Cases 2019年第13期7卷 1703-1710页

作者： Mu-Ni Hu Wei Lv Rui-Yue Hu Yi-Fan Si Xiao-Wen Lu Yan-Juan Deng Huan Deng Medical College Nanchang University Nanchang 330006 Jiangxi Province China Department of Pharmacology Jiangxi Provincial People’s Hospital Nanchang 330006 Jiangxi Province China Department of Gastroenterology the Fourth Affiliated Hospital of Nanchang University Nanchang 330003 Jiangxi Province China Department of Radiology the Fourth Affiliated Hospital of Nanchang University Nanchang 330003 Jiangxi Province China Department of Pathology the Fourth Affiliated Hospital of Nanchang University Nanchang 330003 Jiangxi Province China Molecular Medicine and Genetics Center the Fourth Affiliated Hospital of Nanchang University Nanchang 330003 Jiangxi Province China Renmin Institute of Forensic Medicine in Jiangxi Nanchang 330006 Jiangxi Province China

BACKGROUND Synchronous multiple primary cancers (SMPC) mean two or more malignant tumors occurring simultaneously and with different origins no matter what types they are or where they are located. The carcinogenesis of SMPC often involves variations of some specific genes. However, the correlation between CDH1 mutations and synchronous multiple primary gastrointestinal cancers is largely unknown. CASE SUMMARY A 62-year-old woman had sustained abdominal pain for one week and visited our hospital. Gastrointestinal endoscopy revealed multiple small polypoid lesions in both the stomach and colorectum. Computed tomography and laboratory results were within normal limits. Pathological evaluation confirmed signet ring cell carcinoma without obvious metastatic evidence. Malignant cells showed negativity for E-cadherin and positivity for β-catenin in the cytoplasm and nucleus. DNA sequencing performed on paraffin-embedded tissue revealed two exactly coincident alterations in CDH1, C.57T>G and C.1418A>T. CONCLUSION This case suggests that the combination of CDH1 mutations and WNT/β-catenin signaling activation contributes to the carcinogenesis of gastrointestinal SMPC.

关键词： Multiple primary cancers CDH1 Signet ring cell carcinoma Stomach Colon Case report

Incidence and mortality of primary bone cancers in China, 2014

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Chinese Journal of Cancer Research 2019年第1期31卷 135-143页

作者： Liang Xia Rongshou Zheng Yanjun Xu Xiaojun Xu Siwei Zhang Hongmei Zeng Lifeng Lin Wanqing Chen Institute of Non-communicable Disease Control and Prevention Guangdong Provincial Center for Disease Control and Prevention National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Science and Peking Union Medical College

Objective: In this study, we aimed to estimate the updated incidence and mortality of primary bone cancers based on population-based cancer registration data in 2014, collected by the National Central Cancer Registry of China(NCCRC).Methods: In 2017, 339 registries' data were qualified based on data quality criteria set down by the *** of primary bone cancers were retrieved from the national database. We estimated numbers of primary bone cancer cases and deaths in China using age-specific rates and corresponding national population stratified by area,sex, age-group(0, 1-4, 5-9, 10-14, …, 85+). Chinese standard population in 2000 and Segi's World population were applied for the calculation of age-standardized incidence and mortality ***: In 2014, 24,000 primary bone cancer cases and 17,200 deaths attributable to primary bone cancers were estimated to have occurred in China. The crude incidence rate of primary bone cancers was 1.76/100,000, with agestandardized incidence rate by Chinese standard population(ASIRC) and by World standard population(ASIRW)being 1.35/100,000 and 1.32/100,000, respectively. The crude mortality rate of primary bone cancers was1.26/100,000, with age-standardized mortality rate by Chinese standard population(ASMRC) and by World standard population(ASMRW) being 0.88/100,000 and 0.86/100,000, respectively. Age-specific incidence curve was bimodally distributed with age, with the first peak occurring in the second decade of the life and the second peak in the elderly. Males had higher crude and age-standardized rates for both incidence and mortality compared with females. Both crude and age-standardized incidence rates were higher in rural areas than in urban areas, so were the crude and age-standardized mortality ***: This population-based study presents the most recently available estimates on primary bone cancers in China, revealing that the males are 1.34 times as much as females suffering from primary bone can

关键词： Incidence mortality population-based primary bone cancers

Non-invasive prenatal testing can detect silent cancers in expecting mothers

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Genes & Diseases 2024年第2期11卷 585-588页

作者： Alessandro Ottaiano Monica Ianniello Nadia Petrillo Mariachiara Santorsola Luigia De Falco Salvatore Giovanni Castaldi Maria Antonietta Castaldi Valentina Giudice Carmine Selleri Giovanni Savarese Unit of Innovative Therapies for Abdominal Metastases Istituto Nazionale Tumori di NapoliIRCCS “G.Pascale”Via Mariano SemmolaNapoli 80131Italy AMES Centro Polidiagnostico Strumentale SRLVia Padre Carmine Fico 24Casalnuovo Di Napoli 80013Italy Specialization School of Clinical Pathology Università degli Studi di SalernoVia Giovanni Paolo II 132Fisciano 84084Italy Unit of High-Risk Pregnancy and Prenatal Diagnosis University Hospital “San Giovanni di Dio e Ruggi d'Aragona”Via San LeonardoSalerno 84125Italy Hematology and Transplant Center University Hospital “San Giovanni di Dio e Ruggi d'Aragona”Via San LeonardoSalerno 84125Italy Department of Medicine Surgery and Dentistry“Scuola Medica Salernitana”Via Salvador Allende 43Baronissi 84081Italy

Pregnancy is a unique physiological state in which several changes *** of the most important aspects is the maternal immune system,which sets to tolerate the presence of thedeveloping fetus(a semi-allogeneic organism),while at the same time providing protection against pathogens.1 Pregnancy has long been known to affect the risk of certain cancers including breast cancer in the short term,gestational trophoblastic disease(GTD),cervical cancer,and melanoma.2,3 The reasons for the increased risk of these cancers during pregnancy are not fully understood,but several hypotheses have been proposed as the hormonal and immune system changes.

关键词： mother cancers fetus

Landscape of BRIP1 molecular lesions in gastrointestinal cancers from published genomic studies

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World Journal of Gastroenterology 2020年第11期26卷 1197-1207页

作者： Ioannis A Voutsadakis Algoma District Cancer Program Sault Area HospitalSault Ste MarieON P6B 0A8Canada Section of Internal Medicine Division of Clinical SciencesNorthern Ontario School of MedicineSudburyON P0M 2Z0Canada

BACKGROUND BRIP1 is a helicase that partners with BRCA1 in the homologous recombination(HR) step in the repair of DNA inter-strand cross-link lesions. It is a rare cause of hereditary ovarian cancer in patients with no mutations of BRCA1 or BRCA2. The role of the protein in other cancers such as gastrointestinal(GI) carcinomas is less well characterized but given its role in DNA repair it could be a candidate tumor suppressor similarly to the two BRCA *** To analyze the role of helicase BRIP1(FANCJ) in GI cancers *** Publicly available data from genomic studies of esophageal, gastric, pancreatic,cholangiocarcinomas and colorectal cancers were interrogated to unveil the role of BRIP1 in these carcinomas and to discover associations of lesions in BRIP1 with other more common molecular defects in these *** Molecular lesions in BRIP1 were rare(3.6% of all samples) in GI cancers and consisted almost exclusively of mutations and amplifications. Among mutations,40% were possibly pathogenic according to the Onco KB database. A majority of BRIP1 mutated GI cancers were hyper-mutated due to concomitant mutations in mismatch repair or polymerase ε and δ1 genes. No associations were discovered between amplifications of BRIP1 and any mutated genes. In gastroesophageal cancers BRIP1 amplification commonly co-occurs with ERBB2 *** Overall BRIP1 molecular defects do not seem to play a major role in GI cancers whereas mutations frequently occur in hypermutated carcinomas and co-occur with other HR genes mutations. Despite their rarity, BRIP1 defects may present an opportunity for therapeutic interventions similar to other HR defects.

关键词： BRIP1 FANCJ BACH1 Gastrointestinal cancers Mutations Copy number alterations

Clinical applications of next-generation sequencing in colorectal cancers

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World Journal of Gastroenterology 2013年第40期19卷 6784-6793页

作者： Tae-Min Kim Sug-Hyung Lee Yeun-Jun Chung MRC Cancer Evolution Research Center College of MedicineThe Catholic University of KoreaSeoul 137-701South Korea Integrated Research Center for Genome Polymorphism Department of MicrobiologyCollege of MedicineThe Catholic University of KoreaSeoul 137-701South Korea Department of Pathology College of MedicineThe Catholic University of KoreaSeoul 137-701South Korea

Like other solid tumors,colorectal cancer(CRC) is a genomic disorder in which various types of genomic alterations,such as point mutations,genomic rearrangements,gene fusions,or chromosomal copy number alterations,can contribute to the initiation and progression of the disease. The advent of a new DNA sequencing technology known as next-generation sequencing(NGS) has revolutionized the speed and throughput of cataloguing such cancer-related genomic alterations. Now the challenge is how to exploit this advanced technology to better understand the underlying molecular mechanism of colorectal carcinogenesis and to identify clinically relevant genetic biomarkers for diagnosis and personalized therapeutics. In this review,we will introduce NGS-based cancer genomics studies focusing on those of CRC,including a recent large-scale report from the Cancer Genome Atlas. We will mainly discuss how NGS-based exome-,whole genome- and methylome-sequencing have extended our understanding of colorectal carcinogenesis. We will also introduce the unique genomic features of CRC discovered by NGS technologies,such as the relationship with bacterial pathogens and the massive genomic rearrangements of chromothripsis. Finally,we will discuss the necessary steps prior to development of a clinical application of NGS-related findings for the advanced management of patients with CRC.

关键词： Next-generation sequencing Cancer genomics Colorectal cancers Personalized medicine The cancer genome atlas