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Chinese Medical Journal 2023年第9期136卷 1123-1125页

作者： Xianghong Zhou Shi Qiu Linghui Deng Zilong Zhang Kun Jin Xingyang Su Di Jin Qiming Yuan Chichen Zhang Yifan Li Qiang Wei Lu Yang Birong Dong Department of Urology Institute of UrologyWest China Hospital of Sichuan UniversityChengduSichuan 610041China Institute of Oncology Research(ior) Oncology Institute of Southern Switzerland(IOSI)Bellinzona 6500Switzerland Department of Gerontology West China Hospital of Sichuan UniversityChengduSichuan 610041China

To the Editor:Testosterone is a fundamental male sex hormone produced by the testicular Leydig *** levels are affected by age,peaking in the 20s and 30s and gradually declining thereafter.[1]Low testosterone level may predispose men,especially older men,to a poor prognosis or death in coronavirus disease 2019(COVID-19).[2]Therefore,testosterone levels have a significant impact on the health status of older *** identification of modifiable non-drug factors affecting testosterone levels in older men is important for improving their health.

关键词： testosterone prognosis death

Biological insights in non-small cell lung cancer

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Cancer Biology & Medicine 2023年第7期20卷 500-518页

作者： Rafael Rosell Anisha Jain Jordi Codony-Servat Eloisa Jantus-Lewintre Blake Morrison Jordi Barretina Ginesta María González-Cao Germans Trias i Pujol Research Institute Badalona 08028Spain ior Hospital Quiron-DexeusBarcelona 08028Spain Department of Microbiology JSS Academy of Higher Education&ResearchMysuru 570015India Pangaea Oncology Hospital Quiron-DexeusBarcelona 08028Spain Department of Biotechnology Universitat Politècnica de ValenciaMixed Unit TRIAL(General University Hospital of Valencia Research Foundation and Príncipe Felipe Research Center)CIBERONCValencia 46014Spain Sumitomo Pharma Oncology Inc.CambridgeMA and LehiUT 84043USA

Lung oncogenesis relies on intracellular cysteine to overcome oxidative *** tumor types,including non-small cell lung cancer(NSCLC),upregulate the system x-c cystine/glutamate antiporter(xCT)through overexpression of the cystine transporter SLC7A11,thus sustaining intracellular cysteine levels to support glutathione *** factor erythroid 2-related factor 2(NRF2)serves as a master regulator of oxidative stress resistance by regulating SLC7A11,whereas Kelch-like ECH-associated protein(KEAP1)acts as a cytoplasmic repressor of the oxidative responsive transcription factor *** in KEAP1/NRF2 and p53 induce SLC7A11 activation in *** cystine is crucial in supplying the intracellular cysteine levels necessary to combat oxidative *** in cystine availability lead to iron-dependent lipid peroxidation,thus resulting in a type of cell death called *** inhibitors of xCT(either SLC7A11 or GPX4)induce ferroptosis of NSCLC cells and other tumor *** cystine uptake is impaired,the intracellular cysteine pool can be sustained by the transsulfuration pathway,which is catalyzed by cystathionine-B-synthase(CBS)and cystathionine g-lyase(CSE).The involvement of exogenous cysteine/cystine and the transsulfuration pathway in the cysteine pool and downstream metabolites results in compromised CD8^(+)T cell function and evasion of immunotherapy,diminishing immune response and potentially reducing the effectiveness of immunotherapeutic *** is a previously unrecognized form of regulated cell *** NSCLCs driven by EGFR,ALK,or KRAS,selective inhibitors induce pyroptotic cell death as well as *** targeted therapy,the mitochondrial intrinsic apoptotic pathway is activated,thus leading to the cleavage and activation of ***,gasdermin E is activated,thus leading to permeabilization of the cytoplasmic membrane and cell-lytic pyroptosis(indicated by characte

关键词： Solute carrier family 7 member 11(SLC7A11) nuclear factor erythroid 2-related factor 2(NRF2) ferroptosis pyroptosis KRAS G12C allele-specific inhibitors non-small cell lung cancer(NSCLC)

Identification of the second CFTR mutation in patients with congenital bilateral absence of vas deferens undergoing ART protocols

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Asian Journal of Andrology 2010年第6期12卷 819-826页

作者： Rossella.Giuliani Ivana Antonucci Isabella Torrente Paola Grammatico Giandomenico Palka Liborio Stuppia Department of Clinical Sciences and Bioimages ＇G. d＇Annunzio ＇University Chieti-Pescara 66013 Italy Department of Biomedical Sciences ＇G. d＇Annunzio＇ University Chieti-Pescara 66013 Italy IRCCS CSS-Mendel Institute Rome 00198 Italy Medical Genetics Laboratory Experimental Medicine Department Sapienza S. Camillo-Forlanini Hospital Universityof Rome Rome 00152 Italy Human Genetic Division Pescara Hospital Pescara 65100 Italy I.G.M. CNR c/o IOR Bologna 40136 Italy

Congenital bilateral absence of vas deferens （CBAVD） is a manifestation of the mildest form of cystic fibrosis （CF） and is characterized by obstructive azoospermia in otherwise healthy patients. Owing to the availability of assisted reproductive technology, CBAVD patients can father children. These fathers are at risk of transmitting a mutated allele of the CF transmembrane conductance regulator （CFTR） gene, responsible for CF, to their offspring. The identification of mutations in both CFTR alleles in CBAVD patients is a crucial requirement for calculating the risk of producing a child with full-blown CF if the female partner is a healthy CF carrier. However, in the majority of CBAVD patients, conventional mutation screening is not able to detect mutations in both CFTR alleles, and this difficulty hampers the execution of correct genetic counselling. To obtain information about the most represented CFTR mutations in CBAVD patients, we analysed 23 CBAVD patients, 15 of whom had a single CFTR mutation after screening for 36 mutations and the 5T allele. The search for the second CFTR mutation in these cases was performed by using a triplex approach：（i） first, a reverse dot-blot analysis was performed to detect mutations with regional impact; （ii） next, multiple ligation-dependent probe amplification assays were conducted to search for large rearrangements; and （iii） finally, denaturing high-performance liquid chromatography was used to search for point mutations in the entire coding region. Using these approaches, the second CFTR mutation was detected in six patients, which increased the final detection rate to 60.8%.

关键词： congenital bilateral absence of vas deferens cystic fibrosis transmembrane conductance regulator male infertility

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糖尿病足的病理机制

广州医药 2005年第3期36卷 6-8页

作者：本刊编辑部阎书凤潘巧仪王蕾余浚龙 Luigi Uccioli Department of Endocrinology. University of Rome "TorVergata". Policliwico ior Vergata. Viale Oxford81 0035 Roma(ITALIA)

在西方国家因糖尿病而导致的截肢是非外伤性截肢的主要原因[1].据统计,将近25%的糖尿病患者在一生中都会经受足疾问题,其中1/3将遭受截肢[2-4].

关键词：病理机制糖尿病足外伤性截肢糖尿病患者西方国家

Blockade of integrin signaling reduces chemotherapy-induced premature senescence in collagen cultured bladder cancer cells

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Precision Clinical Medicine 2022年第2期5卷 63-71页

作者： Linghui Deng Kun Jin Xianghong Zhou Zilong Zhang Liming Ge Xingyu Xiong Xingyang Su Di Jin Qiming Yuan Chichen Zhang Yifan Li Haochen Zhao Qiang Wei Lu Yang Shi Qiu National Clinical Research Center of Geriatrics the Center of Gerontology and GeriatricsWest China HospitalSichuan UniversityChengdu 610041China Department of Urology Institute of Urology and National Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityChengdu 610041China West China School of Medicine Sichuan UniversityChengdu 610041China Department of Pharmaceutical and Bioengineering School of Chemical EngineeringSichuan UniversityChengdu 610065China Department of Molecular Oncology Institute of Oncology Research(IOR)Oncology Institute of Southern Switzerland(IOSI)Bellinzona 6500Switzerland

Background:Diminished sensitivity towards chemotherapy remains the major impediment to the clinical treatment of bladder ***,the critical elements in control of chemotherapy resistance remain ***:We adopted improved collagen gels and performed cytotoxicity analysis of doxorubicin(DOX)and mitomycin C(MMC)of bladder cancer cells in a 3D culture *** then detected the expression of multidrug resistant gene ABCB1,dormancy-associated functional protein chicken ovalbumin upstream-transcription factor 1(COUPTF1),cell proliferation marker Ki-67,and cellular senescence marker senescence-associatedβ-galactosidase(SA-β-Gal)in these *** further tested the effects of integrin blockade or protein kinase B(AKT)inhibitor on the senescent state of bladder ***,we examined the tumor growth and survival time of bladder cancer mouse models given the combination treatment of chemotherapeutic agents and integrinα2β1 ligand peptide TFA(TFA).Results:Collagen gels played a repressive role in bladder cancer cell apoptosis induced by DOX and *** mechanism,collagen activated the integrinβ1/AKT cascade to drive bladder cancer cells into a premature senescence state via the p21/p53 pathway,thus attenuating chemotherapy-induced *** addition,TFA had the ability to mediate the switch from senescence to apoptosis of bladder cancer cells in xenograft ***,TFA combined with chemotherapeutic drugs produced a substantial suppression of tumor growth as well as an extension of survival time in ***:Based on our finding that integrinβ1/AKT acted primarily to impart premature senescence to bladder cancer cells cultured in collagen gel,we suggest that integrinβ1 might be a feasible target for bladder cancer eradication.

关键词： premature senescence integrins bladder cancer chemotherapy collagen

Extracellular matrix-derived mechanical force governs breast cancer cell stemness and quiescence transition through integrin-DDR signaling

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Signal Transduction and Targeted Therapy 2023年第7期8卷 3524-3535页

作者： Cong Li Shi Qiu Xiaohan Liu Fengzhu Guo Jingtong Zhai Zhijun Li Linghui Deng Liming Ge Haili Qian Lu Yang Binghe Xu Department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China State Key Laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of Urology Institute of Urology and National Clinical Research Center for GeriatricsWest China Hospital of Sichuan UniversityChengdu 610041China National Clinical Research Center of Geriatrics The Center of Gerontology and GeriatricsWest China HospitalSichuan UniversityChengdu 610065China Institute of Oncology Research(ior) Oncology Institute of Southern Switzerland(IOSI)Bellinzona 6500Switzerland Department of Histology and Embryology Basic Medical CollegeChina Medical UniversityShenyangLiaoning 110122China Department of Pharmaceutical and Bioengineering School of Chemical EngineeringSichuan UniversityChengdu 610065China

The extracellular matrix(ECM)serves as signals that regulate specific cell states in tumor *** evidence suggests that extracellular biomechanical force signals are critical in tumor *** this study,we aimed to explore the influence of ECM-derived biomechanical force on breast cancer cell *** were conducted using 3D collagen,fibrinogen.

关键词： breast cancer matrix

Cell softness reveals tumorigenic potential via ITGB8/AKT/glycolysis signaling in a mice model of orthotopic bladder cancer

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Chinese Medical Journal 2024年第2期137卷 209-221页

作者： Shi Qiu Yaqi Qiu Linghui Deng Ling Nie Liming Ge Xiaonan Zheng Di Jin Kun Jin Xianghong Zhou Xingyang Su Boyu Cai Jiakun Li Xiang Tu Lina Gong Liangren Liu Zhenhua Liu Yige Bao Jianzhong Ai Tianhai Lin Lu Yang Qiang Wei Department of Urology Institute of UrologyNational Clinical Research Center for Geriatrics and Center of Biomedical Big DataWest China Hospital of Sichuan UniversityChengduSichuan 610041China Department of Molecular Oncology Institute of Oncology Research(IOR)Oncology Institute of Southern Switzerland(IOSI)Bellinzona 6500Switzerland Department of Science and Drug Technology University of TurinTurinItaly National Clinical Research Center of Geriatrics The Center of Gerontology and GeriatricsWest China HospitalSichuan UniversityChengduSichuan 610000China Department of Pathology West China HospitalSichuan UniversityChengduSichuan 610041China Department of Pharmaceutics and Bioengineering School of Chemical EngineeringSichuan UniversityChengduSichuan 610000China

Background:Bladder cancer,characterized by a high potential of tumor recurrence,has high lifelong monitoring and treatment *** date,tumor cells with intrinsic softness have been identified to function as cancer stem cells in several cancer ***,the existence of soft tumor cells in bladder tumors remains ***,our study aimed to develop a microbarrier microfluidic chip to efficiently isolate deformable tumor cells from distinct types of bladder cancer ***:The stiffness of bladder cancer cells was determined by atomic force microscopy(AFM).The modified microfluidic chip was utilized to separate soft cells,and the 3D Matrigel culture system was to maintain the softness of tumor *** patterns of integrinβ8(ITGB8),protein kinase B(AKT),and mammalian target of rapamycin(mTOR)were determined by Western *** immunostaining was conducted to examine the interaction between F-actin and tripartite motif containing 59(TRIM59).The stem-cell-like characteristics of soft cells were explored by colony formation assay and in vivo studies upon xenografted tumor ***:Using our newly designed microfluidic approach,we identified a small fraction of soft tumor cells in bladder cancer *** importantly,the existence of soft tumor cells was confirmed in clinical human bladder cancer specimens,in which the number of soft tumor cells was associated with tumor ***,we demonstrated that the biomechanical stimuli arising from 3D Matrigel activated the F-actin/ITGB8/TRIM59/AKT/mTOR/glycolysis pathways to enhance the softness and tumorigenic capacity of tumor ***,we detected a remarkable up-regulation in ITGB8,TRIM59,and phospho-AKT in clinical bladder recurrent tumors compared with their non-recurrent ***:The ITGB8/TRIM59/AKT/mTOR/glycolysis axis plays a crucial role in modulating tumor softness and ***,the soft tumor cells become more sensitive to chemother

关键词： Soft tumor cells 3D Matrigel Stemness Non-muscle invasive bladder neoplasms Microfluidic analytical techniques