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Endoplasmic Reticulum Stress-induced Endothelial Dysfunction Promotes Neointima Formation after Arteriovenous Grafts in Mice on High-fat Diet

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Current Medical Science 2023年第1期43卷 115-122页

作者： Yan-xia ZHONG Chen-chen ZHOU Ying-fang ZHENG Hong-kai DAI Ren-yu CHEN Yu-rou WANG Cheng-ye ZHAN Jin-long LUO Ai-ni XIE Emergency and Intensive Care Unit Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China divison of Cardiothoracic and Vascular Surgery Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China

Objective Endothelial dysfunction is one candidate for triggering neointima formation after arteriovenous grafts(AVGs),but the factors mediating this process are unclear.The purpose of this study was to investigate the role of endoplasmic reticulum stress(ERS)-induced endothelial dysfunction in neointima formation following AVGs in high-fat diet(HFD)mice.Methods CCAAT-enhancer-binding protein-homologous protein(CHOP)knockout(KO)mice were created.Mice were fed with HFD to produce HFD model.AVGs model were applied in the groups of WT ND,WT HFD,and CHOP KO HFD.human umbilical vein endothelial cells(HUVECs)were cultured with oxidized low density lipoprotein(ox-LDL)(40 mg/L)for the indicated time lengths(0,6,12,24 h).ERS inhibitor tauroursodeoxycholic acid(TUDCA)was used to block ERS.Immunohistochemical staining was used to observe the changes of ICAM1.Changes of ERS were detected by real-time RT-PCR.Protein expression levels and ERS activation were detected by Western blotting.Endothellial cell function was determined by endothelial permeability assay and transendothelial migration assay.Results HFD increased neointima formation in AVGs associated with endothelial dysfunction.At the same time,ERS was increased in endothelial cells(ECs)after AVGs in mice consuming the HFD.In vitro,ox-LDL was found to stimulate ERS,increase the permeability of the EC monolayer,and cause endothelial dysfunction.Blocking ERS with TUDCA or CHOP siRNA reversed the EC dysfunction caused by ox-LDL.In vivo,knockout of CHOP(CHOP KO)protected the function of ECs and decreased neointima formation after AVGs in HFD mice.Conclusion Inhibiting ERS in ECs could improve the function of AVGs.

关键词： endoplasmic reticulum stress endothelial dysfunction neointima formation arteriovenous grafts high-fat diet

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Mismatch repair enzyme expression in primary and castrate resistant prostate cancer

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Asian Journal of Urology 2016年第4期3卷 223-228页

作者： Belinda Nghiem Xiaotun Zhang Hung-Ming Lam Lawrence DTrue Ilsa Coleman Celestia SHigano Peter SNelson Colin CPritchard Colm Morrissey Department of Urology University of WashingtonSeattleWAUSA State Key Laboratory of Quality Research in Chinese Medicine Macao Institute for Applied Research in Medicine and HealthMacao University of Science and TechnologyMacao(SAR)China Department of Pathology University of WashingtonSeattleWAUSA divison of human biology Fred Hutchinson Cancer Research CenterSeattleWAUSA Department of Medicine University of WashingtonSeattleWAUSA Department of Laboratory Medicine University of WashingtonSeattleWAUSA

Objective:Although the utility of immunohistochemistry(IHC)for assessing mismatch repair(MMR)protein expression has been demonstrated in solid tumors including primary prostate cancer(PCa),its utility has not been assessed in castration-resistant PCa(CRPC).Methods:Tissue microarrays were constructed from 127 radical prostatectomies and 155 CRPC metastases from 50 patients.MMR(MLH1,MSH2,MSH6,and PMS2)expression was assessed by IHC and gene expression arrays.Associations between MMR protein expression in PCa and CRPC and biochemical recurrence(BCR)or time from diagnosis to death respectively were determined.Results:There was no correlation between levels of MMR protein and BCR.Absence of MSH2 and MSH6 was the most pronounced at 15%and 22%in PCa and 17.8%and 16%in CRPC patients,respectively.MSH2 and MSH6 protein were absent in 9.4%and 8%of PCa and CRPC respectively.Absence of individual MMR proteins did not correlate with BCR or time from diagnosis to death.However absent MSH2/MSH6 in CRPC was associated with shorter time to death(pZ0.0006).Loss of MSH2 was verified at the gene expression level.This finding correlated with microsatellite instability previously reported in this CRPC cohort.

关键词： Mismatch repair Castration resistant prostate cancer MLH1 MSH2 MSH6 PMS2

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Review of magnesium-based biomaterials and their applications

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Journal of Magnesium and Alloys 2018年第1期6卷 23-43页

作者： Nurettin Sezer Zafer Evis Said Murat Kayhan Aydin Tahmasebifar Muammer Koça Sustainable Development divison Hamad Bin Khalifa UniversityQatar FoundationEducation CityDohaQatar Engineering Sciences Middle East Technical UniversityPO Box 06800AnkaraTurkey

In biomedical applications,the conventionally used metallic materials,including stainless steel,Co-based alloys and Ti alloys,often times exhibit unsatisfactory results such as stress shielding and metal ion releases.Secondary surgical operation(s)usually become inevitable to prevent long term exposure of body with the toxic implant contents.The metallic biomaterials are being revolutionized with the development of biodegradable materials including several metals,alloys,and metallic glasses.As such,the nature of metallic biomaterials are transformed from the bioinert to bioactive and multi-biofunctional(anti-bacterial,anti-proliferation,anti-cancer,etc.).Magnesium-based biomaterials are candidates to be used as new generation biodegradable metals.Magnesium(Mg)can dissolve in body fluid that means the implanted Mg can degrade during healing process,and if the degradation is controlled it would leave no debris after the completion of healing.Hence,the need for secondary surgical operation(s)for the implant removal could be eliminated.Besides its biocompatibility,the inherent mechanical properties of Mg are very similar to those of human bone.Researchers have been working on synthesis and characterization of Mg-based biomaterials with a variety of composition in order to control the degradation rate of Mg since uncontrolled degradation could result in loss of mechanical integrity,metal contamination in the body and intolerable hydrogen evolution by tissue.It was observed that the applied methods of synthesis and the choice of components affect the characteristics and performance of the Mg-based biomaterials.Researchers have synthesized many Mg-based materials through several synthesis routes and investigated their mechanical properties,biocompatibility and degradation behavior through in vitro,in vivo and in silico studies.This paper is a comprehensive review that compiles,analyses and critically discusses the recent literature on the important aspects of Mg-based biomaterials.

关键词： Mg-based biomaterials Mechanical properties Implant Biomedical applications Biodegradation

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Intratumor heterogeneity,microenvironment,and mechanisms of drug resistance in glioma recurrence and evolution

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Frontiers of Medicine 2021年第4期15卷 551-561页

作者： Zhaoshi Bao Yongzhi Wang Qiangwei Wang Shengyu Fang Xia Shan Jiguang Wang Tao Jiang Beijing Neurosurgical Institute Capital Medical UniversityBeijing 100050China Department of Neurosurgery Beijing Tiantan HospitalCapital Medical UniversityBeijing 100050China divison of Life Science Department of Chemical and Biological EngineeringCenter for Systems Biology and Human Healthand State Key Laboratory of Molecular NeuroscienceThe Hong Kong University of Science and TechnologyHong KongChina China National Clinical Research Center for Neurological Diseases Beijing 100050China Division of Life Science Hong Kong University of Science and TechnologyHong KongChina Center of Brain Tumor Beijing Institute for Brain DisordersBeijing 100069China Department of Radiotherapy Beijing Tiantan HospitalCapital Medical UniversityBeijing 100050China

Glioma is the most common lethal tumor of the human brain.The median survival of patients with primary World Health Organization grade IV glioma is only 14.6 months.The World Health Organization classification of tumors of the central nervous system categorized gliomas into lower-grade gliomas and glioblastomas.Unlike primary glioblastoma that usually develop de novo in the elderly,secondary glioblastoma enriched with an isocitrate dehydrogenase mutant typically progresses from lower-grade glioma within 5-10 years from the time of diagnosis.Based on various evolutional trajectories brought on by clonal and subclonal alterations,the evolution patterns of glioma vary according to different theories.Some important features distinguish the normal brain from other tissues,e.g.,the composition of the microenvironment around the tumor cells,the presence of the blood-brain barrier,and others.The underlying mechanism of glioma recurrence and evolution patterns of glioma are different from those of other types of cancer.Several studies correlated tumor recurrence with tumor heterogeneity and the immune microenvironment.However,the detailed reasons for the progression and recurrence of glioma remain controversial.In this review,we introduce the different mechanisms involved in glioma progression,including tumor heterogeneity,the tumor microenvironment and drug resistance,and their pre-clinical implements in clinical trials.This review aimed to provide new insights into further clinical strategies for the treatment of patients with recurrent and secondary glioma.

关键词： glioma evolution mechanism strategies tumor heterogeneity secondary glioma

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Suppressing tumor growth of nasopharyngeal carcinoma by hTERTC27 polypeptide delivered through adeno-associated virus plus adenovirus vector cocktail

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Chinese Journal of Cancer 2012年第12期31卷 588-597页

作者： Xiong Liu Xiang-Ping Li Ying Peng Samuel S.Ng Hong Yao Zi-Feng Wang Xiao-Mei Wang Hsiang-Fu Kung Marie C.M. Lin Department of Otolaryngology Nanfang Hospital Nanfang Medical UniversityGuangzhou Guangdong 510515 P. R. China Department of Neurology The Sun Yat-sen Memorial Hospital Sun Yat-sen UniversityGuangzhou Guangdong 510120 P. R. China Brain Tumor Center Divison of Neurosurgery Department of Surgery The Chinese University of Hong KongShatin Hong Kong China Center for Emerging Infectious Diseases The Chinese University of Hong Kong ShatinHong Kong P. R. China Medical College Shenzhen UniversityShenzhen Guangdong 518061 P. R. China

Nasopharyngeal carcinoma(NPC) is a metastatic carcinoma that is highly prevalent in Southeast Asia. Our laboratory has previously demonstrated that the C-terminal 27-kDa polypeptide of human telomerase reverse transcriptase (hTERTC27) inhibits the growth and tumorigenicity of human glioblastoma and melanoma cells. In this study, we investigated the antitumor effect of hTERTC27 in human C666-1 NPC cells xenografted in a nude mouse model. A cocktail of vectors comprising recombinant adeno-associated virus (rAAV) and recombinant adenovirus (rAdv) that each carry hTERTC27 (rAAV-hTERTC27 and rAdv- hTERTC27; the cocktail was abbreviated to rAAV/rAdv-hTERTC27) was more effective than either rAAV- hTERTC27 or rAdv-hTERTC27 alone in inhibiting the growth of C666-1 NPC xenografts. Furthermore, we established three tumors on each mouse and injected rAAV/rAdv-hTERTC27 into one tumor per mouse. Although hTERTC27 expression could only be detected in the injected tumors, reduced tumor growth was observed in the injected tumor as well as the uninjected tumors, demonstrating that the vector cocktail could provoke an antitumor effect on distant, metastasized tumors. Further studies showed the observed antitumor effects included inducing necrosis and apoptosis and reducing microvessel density. Together, our data suggest that the rAAV/rAdv-hTERTC27 cocktail can potently inhibit NPC tumor growth in both local and metastasized tumors and should be further developed as a novel gene therapy strategy for NPC.

关键词：重组腺相关病毒抑制肿瘤生长抑制腺病毒载体鸡尾酒鼻咽癌多肽人端粒酶逆转录酶

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MET fusions and splicing variants convergently defne a subgroup of glioma sensitive to MET inhibitors

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Holistic Integrative Oncology 2022年第1期1卷 244-254页

作者： Ke-Nan Zhang Zheng Zhao Jing Chen Zhaoshi Bao Rui-Chao Chai Zhiyan Sun Lingxiang Wu Zhiliang Wang Hanjie Liu Quanhua Mu Huimin Hu Fan Zeng Zheng Wang Guanzhang Li Yuanhao Chang Qiangwei Wang Fan Wu Ying Zhang Yuqing Liu Chunjie Jiang Ulf Dietrich Kahlert Do-Hyun Nam Wei Zhang Chunsheng Kang Jiguang Wang Rongjie Tao Qianghu Wang Tao Jiang Beijing Neurosurgical Institute Capital Medical UniversityBeijingChina Department of Neurosurgery Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Department of Bioinformatics Nanjing Medical UniversityNanjingJiangsuChina Department of Chemical and Biological Engineering Divison of Life ScienceCenter for Systems Biology and Human Healthand State Key Laboratory of Molecular NeuroscienceThe Hong Kong University of Science and TechnologyHong KongChina Division of Diabe‑tes Endocrinologyand MetabolismDepartment of MedicineBaylor College of MedicineHoustonTXUSA Molecular and Experimental Surgery Faculty of Medicine and University Medicine MagdeburgMagdeburgGermany Institute for Refractory Cancer Research Samsung Medical CenterSeoulRepublic of Korea Department of Health Science&Technology Samsung Advanced Institute for Health Sciences&Technology(SAIHST)Sungkyunkwan UniversitySeoulRepublic of Korea Department of Neurosurgery Samsung Medical CenterSungkyunkwan University School of MedicineSeoulRepublic of Korea Laboratory of Neuro‑Oncology Ministry of Education and Tianjin CityTianjin Neurological InstituteTianjin Medical University General HospitalKey Laboratory of PostNeuro Injury Neuro-Repair and Regeneration in Central Nervous SystemTianjinChina Departments of Neurosurgery Shandong Cancer Hospital and InstituteShandong UniversityJinanShandongChina Center of Brain Tumor Beijing Institute for Brain DisordersBeijingChina China National Clinical Research Center for Neurological Diseases BeijingChina Research Unit of Accurate Diagnosis Treatmentand Translational Medicine of Brain TumorsChinese Academy of Medical SciencesBeijingChina

Purpose:Our previous study has shown that PTPRZ1-MET(ZM)fusion is a viable target for MET inhibitors in gliomas.However,the diversity and prevalence of somatic MET alterations in difuse gliomas are still elusive and need to be extensively characterized for identifying novel therapeutic targets.Methods:Totally,1,350 glioma patients and 31 patient-derived cells were collected from the Chinese Glioma Genome Atlas(CGGA)and published data.All kinds of MET fusions and/or splicing variants(MET F/SVs)were identifed by bioinformatical methods.Single-cell RNA sequencing(scRNA-seq)were used for validation.In vitro experiments of drug resistance were conducted for the possibility of MET-targeted treatment.Results:MET F/SVs but not genomic amplifcation,were highly enriched in the secondary glioblastomas(sGBM)and marked worse prognosis.Further molecular and scRNA-seq analysis revealed that MET F/SVs were induced in the course of glioma evolution and highly associated with MET overexpression.Subsequent in vitro and the clinical study showed that cells and patients harboring MET F/SVs have better response to MET inhibitors.Conclusion:Our fndings expanded the percentage of gliomas with abnormal MET alterations and suggested that a subgroup of gliomas harboring MET F/SVs may beneft from MET-targeted therapy.

关键词： MET variation Secondary glioblastoma Biomarker MET inhibitor Precision neuro-oncology

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美洲钝眼蜱幼虫叮咬导致多发性瘙痒性丘疹

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世界核心医学期刊文摘（皮肤病学分册） 2006年第8期2卷 26-27页

作者： Fisher E.J. Lucky A.W. 王琼 divison of Pediatric Dermatology University of Cincinnati School of Medicine Pavilion A 234 Goodman Ave Cincinnati OH 45267 United States Dr.

Background: Ticks are the second most common vectors of human infectious diseases in the world. In addition to their role as vectors, ticks and their larvae can also produce primary skin manifestations. Infestation by the larvae of ticks is not commonly recognized, with only 3 cases reported in the literature. The presence of multiple lesions and partially burrowed 6-legged tick larvae can present a diagnostic challenge for clinicians. Observation: We describe a 51-year-old healthy woman who presented to our clinic with multiple erythematous papules and partially burrowed organisms 5 days after exposure to a wooded area in southern Kentucky. She was treated with permethrin cream and the lesions resolved over the following 3 weeks without sequelae. The organism was later identified as the larva of Amblyommaspecies, the lone star tick. Conclusions: Multiple pruritic papules can pose a diagnostic challenge. The patient described herein had an unusually large number of pruritic papules as well as tick larvae present on her skin. Recognition of lone star tick larvae as a cause of multiple bitesmay be helpful in similar cases.

关键词：红斑丘疹多发性幼虫美洲瘙痒性蜱叮咬皮肤表现文献报道临床医师

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Assessment of Lung Cancer Risk on the Basis of a Biomarker Panel of Circulating Proteins

Assessment of Lung Cancer Risk on the Basis of a Biomarker P...

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2019年中国肿瘤标志物学术大会暨第十三届肿瘤标志物青...

作者： sun,nan Florence,Guida Bantis,LeonidasE. Muller,DavidC. Li,Peng Taguchi,Ayumu Dhillon,Dilsher Kundnani,DeepaliL. Patel,NikulJ. Yan,Qingxiang Byrnes,Graham Moons,KarelG.M. Tj?nneland,Anne Panico,Salvatore Claudia ,Agnoli Vineis,Paolo Palli,Domenico Bueno-de-Mesquita,Bas Peeters,PetraH. Agudo,Antonio Huerta,JoseM. Dorronsoro,Miren Barranco,MiguelRodriguez Ardanaz,Eva Travis,RuthC. Byrne,KarlSmith Boeing,Heiner Steffen,Annika Kaaks,Rudolf Hüsing,Anika Trichopoulou,Antonia Lagiou,Pagona LaVecchia,Carlo Severi,Gianluca Boutron-Ruault,Marie-Christine Sandanger,TorkjelM. Weiderpass,Elisabete N?st,ThereseH. Tsilidis,Kostas Riboli,Elio Grankvist,Kjell Johansson,Mikael Goodman,GaryE. Feng,Ziding Brennan,Paul Johansson,Mattias Hanash,Samir M. The University of Texas MD Anderson Cancer Center Genetic Epidemiology Group International Agency for Research on Cancer Department of Biostatistics The University of Texas MD Anderson Cancer Center Department of Epidemiology and Biostatistics Imperial College London School of Public Health Laboratory of Population Health Max Planck Institute for Demographic Research Department of Translational Molecular Pathology The University of Texas MD Anderson Cancer Center Environment and Radiation Section International Agency for Research on Cancer Department of Epidemiology Julius Center for Health Sciences and Primary CareUniversity Medical Center Unit of Diet Genesand EnvironmentDanish Cancer Society Research Center Department of Clinical Medicine and Surgery Federico Ⅱ University Epidemiology and Prevention Unit Fondazione IRCCS Istituto Nazionale dei Tumori Molecular and Genetic Epidemiology Unit Human Genetics Foundation Cancer Risk Factors and Life-Style Epidemiology Unit Cancer Research and Prevention Institute-Istituto per lo Studio ela Prevenzione Oncologica Department for Determinants of Chronic Diseases National Institute for Public Health and the Environment Unit of Nutirition and Cancer Cancer Epidemiology Research ProgramCatalan Institute of OncologyBellvitge Institute for Biomedical Research (IDIBELL)L’Hospitalet de Llobregat Department of Epidemiology Murcia Regional Health Council Biomedical Research Institute of Murcia(IMIB-Arrixaca) Centro de Investigación Biomédica en Red Epidemiología y Salud Pública (CIBERESP) Public Health Direction and Biodonostia Research Institute-CIBERESP Escuela Andaluza de Salud Pública Instituto de Investigación Biosanitaria Hospitales Universitarios de Granada/Universidad de Granada Epidemiology Preventionand Promotion Health ServiceNavarra Public Health Institute Instituto de Investigación Sanitaria de Navarra (IdiSNA) Navarra Institute for Health Research Cancer Epidemiology Unit Nuffield Department of Population HealthUniversity of Oxford Department of Epidemi

IMPORTANCE:There is an urgent need to improve lung cancer risk assessment because current screening criteria miss a large proportion of cases.OBJECTIVE:To investigate whether a lung cancer risk prediction model based on a panel of selected circulating protein biomarkers can outperform a traditional risk prediction model and current US screening criteria.

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