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Glutamate in cancers:from metabolism to signaling

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The Journal of Biomedical Research 2020年第4期34卷 260-270页

作者： Haowei Yi Geoff Talmon Jing Wang Department of Genetics Cell Biology and AnatomyUniversity of Nebraska Medical CenterOmahaNE 68198USA. Department of Pathology and Microbiology University of Nebraska Medical CenterOmahaNE 68198USA. Eppley Institute for Research in Cancer and Allied Diseases University of Nebraska Medical CenterOmahaNE 68198USA.

Glutamine and glutamate are major bioenergy substrates for normal and cancer cell growth.Cancer cells need more biofuel than normal tissues for energy supply,anti-oxidation activity and biomass production.Genes related to metabolic chains in many cancers are somehow mutated,which makes cancer cells more glutamate dependent.Meanwhile,glutamate is an excitatory neurotransmitter for conducting signals through binding with different types of receptors in central neuron system.Interestingly,increasing evidences have shown involvement of glutamate signaling,guided through their receptors,in human malignancy.Dysregulation of glutamate transporters,such as excitatory amino acid transporter and cystine/glutamate antiporter system,also generates excessive extracellular glutamate,which in turn,activates glutamate receptors on cancer cells and results in malignant growth.These features make glutamate an attractive target for anti-cancer drug development with some glutamate targeted but blood brain barrier impermeable anti-psychosis drugs under consideration.We discussed the relevant progressions and drawbacks in this field herein.

关键词： glutamate cancers metabolism glutamate receptors glutamate transporters

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 cancers.Mammaglobin-A(Mam-A),which is overexpressed in most breast carcinomas,has been proposed as a promising target.However,the lack of specific targeting moieties due to uncertain binding epitopes hampers further translational study.Here,seven potential epitopes of Mam-A were disclosed,and a unique epitope was then identified in most types of breast cancers,despite the genotypic heterogeneity.With 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 cancers.The 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

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 proteins.AIM To analyze the role of helicase BRIP1(FANCJ) in GI cancers pathogenesis.METHODS 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 cancers.RESULTS 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 amplification.CONCLUSION 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

Roles of ribosomal proteins in hematologic disorders and cancers:a review

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Emergency and Critical Care Medicine 2023年第1期3卷 23-31页

作者： Jie Wang Feng Yan Shandong Key Laboratory of Cardiovascular Proteomics Department of Geriatric MedicineQilu Hospital of Shandong UniversityJinanChina Department of Emergency Medicine Qilu Hospital of Shandong UniversityJinanChina

Ribosomes are important organelles for synthesizing proteins in cells.They are composed of ribosomal RNA and more than 80 ribosomal proteins.It is well known that an essential function of ribosomal proteins is to participate in protein translation.In addition,ribosomal proteins also perform extra-ribosomal functions,such as participating in DNA replication,transcription,and damage repair,regulating cell growth,proliferation,apoptosis,and transformation.In recent years,studies have shown that alterations in ribosomal protein synthesis or function can lead to various hematologic diseases,including Diamond-Blackfan anemia,5q-syndrome,Shwachman-Diamond syndrome,and other blood system diseases.Moreover,abnormal expressions of specific ribosomal protein genes have been reported in many malignant tumors.In this review,we elaborated on the changes in ribosomal proteins in hepatocellular carcinoma and colorectal,prostate,gastric,esophageal,and other cancers and discussed the relationship between ribosomal proteins and the occurrence of hematologic disorders and cancers.

关键词： cancers Extra-ribosomal function Hematologic diseases Ribosomal protein Ribosome

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 NCCRC.Cases 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 rates.Results: 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 rates.Conclusions: 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 cancers and the adolescents in puberty and the elde

关键词： Incidence mortality population-based primary bone cancers

Association of metabolic NCD risk factors with oral, breast and cervical precancers and cancers in India

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Family Medicine and Community Health 2019年第4期7卷 37-45页

作者： Ashwini Kedar Roopa Hariprasad Vipin Kumar Kavitha Dhanasekaran Ravi Mehrotra Department of Clinical Oncology National Institute of Cancer Prevention and ResearchNoidaIndia

Objective To find an association between metabolic non-communicable disease(NCD)risk factors(high blood pressure(BP),high random blood sugar(RBS)and overweight/obesity)and oral,breast,cervical cancers/precancerous or potentially malignant conditions.Design This is an observational study using convenience sampling.The participants were screened through opportunistic or population-based screening.setting The study was conducted at a health promotion clinic(HPC)located in Northern India under the Indian Council of Medical Research.HPC is a screening clinic where screening is done for hypertension(HT),diabetes mellitus(DM),obesity,and oral,breast and cervical cancers.The study was conducted between December 2016 and January 2019.Participant The number of participants screened was 8352(6712 women and 1640 men).All consenting men and women above 18 years were included.All participants were screened for oral cancer,DM,HT and obesity.All women were also screened for breast and cervical cancers.Cervical screening was done for non-pregnant women 21 years and above with history of sexual activity.result Oral potentially malignant disease(OPMD)was the most prevalent,followed by breast cancer,oral cancer,cervical cancer and cervical precancer.High RBS had a strong association with oral cancer(OR=2.29,95%CI 1.09 to 4.82,p=0.03)and breast cancer(OR=1.95,95%CI 1.01 to 3.76,p=0.05).High BP had a strong association with breast cancer(OR=2.50,95%CI 1.43 to 4.35,pcancers.Besides NCD risk factors,current tobacco use was a strong determinant of OPMD and oral cancer.Hence,primary and primor

关键词： cervical breast 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 occur.One 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

Model systems to study the life cycle of human papillomaviruses and HPV-associated cancers

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Virologica Sinica 2015年第2期30卷 92-100页

作者： Louise T.Chow Department of Biochemistry and Molecular Genetics University of Alabama at Birmingham Birmingham 35294-0005 USA

The prevalent human papillomaviruses(HPVs) infect either cutaneous or mucosal epithelium. Active Infections lead to epithelial hyperprolifeation and are usually cleared in healthy individuals within a year. Persistent infections in the anogenital tracts by certain high-risk genotypes such as HPV-16, HPV-18 and closely related types, can progress to high grade dysplasias and carcinomas in women and men, including cervical, vulva, penile and anal cancers. A significant fraction of the head and neck cancers are also caused by HPV-16. The viral oncogenes responsible for neoplastic conversion are E6 and E7 that disrupt the pathways controlled by the two major tumor suppressor genes, p53 and members of p RB family. Because HPV cannot be propagated in conventional submerged monolayer cell cultures, organotypic epithelial raft cultures that generate a stratified and differentiated epithelium have been used to study the viral life cycle. This article describes several systems to examine aspects of the viral productive phase, along with the advantages and limitations. Animal model systems of HPV carcinogenesis are also briefly described.

关键词： human papillomaviruses(HPVs) productive program HPV-associated cancers model systems

Clinical features of second primary cancers arising in earlygastric cancer patients after endoscopic resection

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World Journal of Gastroenterology 2015年第27期21卷 8358-8365页

作者： Jung-Wook Kim Jae-Young Jang Young Woon Chang Yong Ho Kim Department of Internal Medicine College of Medicine Kyung Hee University Department of Surgery College of Medicine Kyung Hee University

AIM: To investigate the incidence and distribution of second primary cancers(SPCs) in early gastric cancer(EGC) patients who underwent endoscopic resection(ER), compared to advanced gastric cancer(AGC) patients who underwent surgery.METHODS: The medical records of 1021 gastric cancer(GC) patients were retrospectively reviewed from January 2006 to December 2010. The characteristics and incidence of SPCs were investigated in those with EGC that underwent curative ER(the EGC group) and those with AGC who underwent curative surgical resection(the AGC group).RESULTS: We ultimately enrolled 184 patients in the EGC group and 229 patients in the AGC group. A total of 38 of the 413(9.2%) GC patients had SPCs; the rate was identical in both groups. Of these 38 patients, 18 had synchronous and 20 had metachronous cancers. The most common SPC was lung cancer(18.4%), followed by colorectal cancer(13.2%) and esophageal cancer(13.2%). No significant risk factors were identified for the development of SPCs.CONCLUSION: Endoscopists should provide close surveillance and establish follow-up programs to ensure SPC detection in GC patients undergoing curativeresection regardless of their clinical characteristics.

关键词： Second primary cancers Early gastric cancer Endoscopic resection Advanced gastric cancer