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Cancer stem cell-targeted chimeric antigen receptor(CAR)-T cell therapy: Challenges and prospects

Acta Pharmaceutica Sinica B 2021年第7期11卷 1721-1739页

作者： Javad Masoumi Abdollah Jafarzadeh Jalal Abdolalizadeh Haroon Khan Jeandet Philippe Hamed mirzaei hamid reza mirzaei Department of Immunology School of MedicineRafsanjan University of Medical SciencesRafsanjan ***Iran Department of Immunology School of MedicineKerman University of Medical SciencesKerman ***Iran Drug Applied Research Center Tabriz University of Medical SciencesTabriz ***Iran Department of Pharmacy Abdul Wali Khan UniversityMardan 23200Pakistan Research Unit“Induced Resistance and Plant Bioprotection” EA 4707SFR Condorcet FR CNRS 3417Faculty of Sciences University of Reims Champagne-ArdenneBP 103951687Reims Cedex 2France Research Center for Biochemistry and Nutrition in Metabolic Diseases Institute for Basic SciencesKashan University of Medical SciencesKashan ***Iran Department of Medical Immunology School of MedicineTehran University of Medical SciencesTehran ***Iran

Cancer stem cells(CSCs)with their self-renewal ability are accepted as cells which initiate *** are regarded as interesting targets for novel anticancer therapeutic agents because of their association with tumor recurrence and resistance to conventional therapies,including radiotherapy and *** antigen receptor(CAR)-T cells are engineered T cells which express an artificial receptor specific for tumor associated antigens(TAAs)by which they accurately target and kill cancer *** recent years,CAR-T cell therapy has shown more efficiency in cancer treatment,particularly regarding blood *** expression of specific markers such as TAAs on CSCs in varied cancer types makes them as potent tools for CAR-T cell *** we review the CSC markers that have been previously targeted with CAR-T cells,as well as the CSC markers that may be used as possible targets for CAR-T cell therapy in the ***,we will detail the most important obstacles against CART cell therapy and suggest solutions.

关键词： Chimeric antigen receptor T cell Cancer stem cell Immunotherapy Tumor associated antigens Combination therapy Off-tumor toxicity Clinical trial Tumor immunosuppressive microenvironment

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The Hippo Tumor Suppressor Pathway(YAP/TAZ/TEAD/MST/LATS)and EGFR-RAS-RAF-MEK in cancer metastasis

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Genes & Diseases 2021年第1期8卷 48-60页

作者： Mohammad reza Zinatizadeh Seyed Rouhollah Miri Peyman Kheirandish Zarandi Ghanbar Mahmoodi Chalbatani Catarina Raposo hamid reza mirzaei Mohammad Esmaeil Akbari Habibollah Mahmoodzadeh Cancer Research Center Shahid Beheshti University of Medical SciencesTehranIran Cancer Research Center Cancer Institute of IranTehran University of Medical ScienceTehranIran Department of Immunology School of MedicineTehran University of Medical SciencesTehranIran Department of Immunology Medical SchoolShahid Beheshti University of Medical SciencesTehranIran Faculty of Pharmaceutical Sciences State University of Campinas-UNICAMP Campinas SPBrazil Cancer Research Center Shohadae Tajrish HospitalDepartment of Radiation OncologyShahid Beheshti University of Medical SciencesTehranIran

Hippo Tumor Suppressor Pathway is the main pathway for cell growth that regulates tissue enlargement and organ size by limiting cell *** pathway is activated in response to cell cycle arrest signals(cell polarity,transduction,and DNA damage)and limited by growth factors or mitogens associated with EGF and *** major pathway consists of the central kinase of Ste20 MAPK(Saccharomyces cerevisiae),Hpo(Drosophila melanogaster)or MST kinases(mammalian)that activates the mammalian AGC kinase dmWts or LATS effector(MST and LATS).YAP in the nucleus work as a cofactor for a wide range of transcription factors involved in proliferation(TEA domain family,TEAD1-4),stem cells(Oct4 mononuclear factor and SMAD-related TGFb effector),differentiation(RUNX1),and Cell cycle/apoptosis control(p53,p63,and p73 family members).This is due to the diverse roles of YAP and may limit tumor progression and *** also coordinates various signal transduction pathways such as Hippo,WNT,TGFb and EGFR,and effects on lack of regulation of TEAD cancerous genes,such as KRAS,BRAF,LKB1,NF2 and MYC,which play essential roles in tumor progression,metastasis,cancer metabolism,immunity,and drug ***,RAS signaling is a pivotal factor in the inactivation of Hippo,which controls EGFR-RAS-RAF-MEK-ERKmediated interaction of Hippo ***,the loss of the Hippo pathway may have significant consequences on the targets of RAS-RAF mutations in cancer.

关键词： Cancer Hippo pathway Metastasis Signaling Tumor suppressor

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The Role and Function of Ras-association domain family in Cancer:A Review

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Genes & Diseases 2019年第4期6卷 378-384页

作者： Mohammad reza Zinatizadeh Seyed Ali Momeni Peyman Kheirandish Zarandi Ghanbar Mahmoodi Chalbatani Hassan Dana hamid reza mirzaei Mohammad Esmaeil Akbari Seyed Rouhollah Miri Cancer Research Center Shahid Beheshti University of Medical SciencesTehranIran Cancer Research Center Cancer Institute of IranTehran University of Medical ScienceTehranIran Uro-Oncology Research Center Tehran University of Medical SciencesTehranIRIran Cancer Research Center Shohadae Tajrish HospitalDepartment of Radiation OncologyShahid Beheshti University of Medical SciencesTehranIran

Ras gene mutation has been observed in more than 30%of cancers,and 90%of pancreatic,lung and colon *** proteins(K-Ras,H-Ras,N-Ras)act as molecular switches which are activated by binding to *** play a role in the cascade of cell process control(proliferation and cell division).In the inactive state,transforming GTP to GDP leads to the activation of GTpase in Ras ***,the mutation in Ras leads to the loss of internal GTPase activity and permanent activation of the *** activated Ras can promote the cell death or stop cell growth,which are facilitated by Ras-association domain *** studies have been conducted to determine the importance of losing RASSF proteins in Rasinduced *** paper examines the role of Ras and RASSF *** general,RASSF proteins can be used as a suitable means for targeting a large group of Ras-induced tumors.

关键词： Cancer Colon H-Ras K-Ras Lung N-Ras Pancreatic

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CAR-T cells: Early successes in blood cancer and challenges in solid tumors

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Acta Pharmaceutica Sinica B 2021年第5期11卷 1129-1147页

作者： Hassan Dana Ghanbar Mahmoodi Chalbatani Seyed Amir Jalali hamid reza mirzaei Stephan A.Grupp Eloah Rabello Suarez Catarina Raposo Thomas J.Webster Cancer Research Center Cancer Institute of IranTehran University of Medical SciencesTehran 13145-158Iran Department of Medical Immunology School of MedicineTehran University of Medical SciencesTehran ***Iron Department of Immunology School of MedicineShahid Beheshti University of Medical SciencesTehran ***Iran Division of Oncology Department of Pediatricsthe Children's Hospital of PhiladelphiaPhiladelphiaPA 19104USA Center for Natural and Human Sciences Federal University of ABCSanto AndreSP 09210-580Brazil Faculty of Pharmaceutical Sciences State University of Campinas(UNICAMP)CampinasSP 13083-87JBrazil Department of Chemical Engineering Northeastern UniversityBostonMA 02115USA

New approaches to cancer immunotherapy have been developed, showing the ability to harness the immune system to treat and eliminate cancer. For many solid tumors, therapy with checkpoint inhibitors has shown promise. For hematologic malignancies, adoptive and engineered cell therapies are being widely developed, using cells such as T lymphocytes, as well as natural killer(NK) cells, dendritic cells, and potentially others. Among these adoptive cell therapies, the most active and advanced therapy involves chimeric antigen receptor(CAR)-T cells, which are T cells in which a chimeric antigen receptor is used to redirect specificity and allow T cell recognition, activation and killing of cancers, such as leukemia and lymphoma. Two autologous CAR-T products have been approved by several health authorities,starting with the U.S. Food and Drug Administration(FDA) in 2017. These products have shown powerful, inducing, long-lasting effects against B cell cancers in many cases. In distinction to the results seen in hematologic malignancies, the field of using CAR-T products against solid tumors is in its infancy. Targeting solid tumors and trafficking CAR-T cells into an immunosuppressive microenvironment are both significant challenges. The goal of this review is to summarize some of the most recent aspects of CAR-T cell design and manufacturing that have led to successes in hematological malignancies, allowing the reader to appreciate the barriers that must be overcome to extend CAR-T therapies to solid tumors successfully.

关键词： Immunotherapy T cell therapy Chimeric antigen receptor(CAR) Genetic engineering

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Characteristics of turbulent flow in 3-D pools in the presence of submerged rigid vegetation in channel bed

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Journal of Hydrodynamics 2024年第1期36卷 158-169页

作者： Kourosh Nosrati Hossein Afzalimehr Jueyi Sui hamid reza Reisifar Natural Disasters Prevention Research Center Faculty of Civil EngineeringIran University of Science and TechnologyTehranIran School of Engineering University of Northern British ColumbiaPrince GeorgeCanada

In this study,the interaction between 3-D bedforms and submerged rigid vegetation has been *** laboratory experiments were conducted to study the distribution of flow velocity,Reynolds shear stress,turbulent kinetic energy,and skewness coefficients for a constant density of *** showed that the velocity profile in the pool section deviates from those in the upstream section of the *** has been found that the dip parameter varied between 0.6H and 0.9H depending on various factors including bed roughness,vegetation distribution,and pool entrance/exit ***,scattered vegetation in the pool and differences in slopes created non-uniform flow ***,in the wake region behind each vegetated element,flow velocity reduced significantly,and small-scale eddies are formed,causing increased *** decreasing the entrance slope and bed roughness,relatively uniform flow and weaker turbulence was resulted,but the random distribution of vegetated elements counteracted this balance and intensified *** the decrease in the pool entrance slope,the contribution of sweep event decreased and the contribution of ejection event increased.

关键词： Submerged rigid vegetation 3-D pool Reynolds shear stress skewness coefficients

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Effects of heat stress and long photoperiod on the prostate of rats

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Asian pacific Journal of Reproduction 2024年第4期13卷 187-196页

作者： hamid reza Ghaffari Javad Poursamimi Department of Basic Sciences School of MedicineZabol University of Medical SciencesZabolIran Department of Immunology Faculty of MedicineZabol University of Medical SciencesZabolIran

Objective:To examine light and heat effects on the morphological,histological,and micrometric structure of the prostate of ***:Thirty adult male rats were divided into three *** control group was kept under 20℃-22℃ and an artificial 12 h/12 h day/night cycle;the temperature group was under normal light and at(42±1)℃ heat for 4 to 5 h daily,and the light group was exposed to 8 h/16 h day/night cycle with 20℃-22℃.Rats were weighed five times(at the beginning of the study and every seven days).Five milliliters(mL)of their peripheral blood were *** tissue staining was performed using the hematoxylin-eosin(H&E)stain and periodic acid-Schiff(PAS).In the following,tissue and cellular reactions to the PAS were ***:Folds were located entirely on the surface of the anterior lobe and periphery of the other *** secretory units in the anterior lobe were more than the lateral lobe.A strong reaction of the secretory cells to the PAS was *** serum levels of the light group also significantly increased compared to the control group(P<0.05).The most histometric changes of the lobes were established in the lateral *** stress resulted in a significant decrease in testosterone levels and transformed prostate *** epithelium and parenchyma to scaffold ratio in the temperature group ***:Maximum and minimum changes in the ventral lobe happened under the ascent of temperature and light,*** ventral lobe in the study of prostatic hyperplasia should be more considered.

关键词： Prostate Heat stress Photoperiod Histology Testosterone Rat

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Effect of CO_(2)exposure on the mechanical strength of geopolymerstabilized sandy soils

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Journal of Rock Mechanics and Geotechnical Engineering 2024年第2期16卷 670-681页

作者： hamid reza Razeghi Armin Geranghadr Fatemeh Safaee Pooria Ghadir Akbar A.Javadi School of Civil Engineering Iran University of Science and TechnologyTehran***Iran Department of Engineering University of ExeterExeterEX44QFUK

In recent years,there has been growing interest in developing methods for mitigating greenhouse effect,as greenhouse gas emissions continue to contribute to global temperature *** the other hand,investigating geopolymers as environmentally friendly binders to mitigate the greenhouse effect using soil stabilization has been widely ***,the effect of CO_(2)exposure on the mechanical properties of geopolymer-stabilized soils is rarely *** this context,the effect of CO_(2)exposure on the mechanical and microstructural features of sandy soil stabilized with volcanic ash-based geopolymer was *** factors were concerned,for example the binder content,relative density,CO_(2)pressure,curing condition,curing time,and carbonate *** results showed that the compressive strength of the stabilized sandy soil specimens with 20%volcanic ash increased from 3 MPa to 11 *** was also observed that 100 kPa CO_(2)pressure was the optimal pressure for strength development among the other *** mechanical strength showed a direct relationship with binder content and carbonate ***,in the ambient curing(AC)condition,the mechanical strength and carbonate content increased with the curing ***,the required water for carbonation evaporated after 7 d of oven curing(OC)condition and as a result,the 14-d cured samples showed lower mechanical strength and carbonate content in comparison with 7-d cured ***,the rate of strength development was higher in OC cured samples than AC cured samples until 7 d due to higher geopolymerization and carbonation rate.

关键词： Soil stabilization CO_(2)effect Geopolymer

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Exploring the relationship between ambient sulfur dioxide and semen quality parameters:A systematic review and meta-analysis

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Asian pacific Journal of Reproduction 2024年第1期13卷 12-21页

作者： Seyed Sobhan Bahreiny Mojtaba Aghaei Mohammad reza Dabbagh hamid Ghorbani Moslem Javidan reza Mohammadpour Fard Student Research Committee Ahvaz Jundishapur University of Medical SciencesAhvazIran Medical Basic Sciences Research Institute Physiology Research CenterDepartment of PhysiologySchool of MedicineAhvaz Jundishapur University of Medical SciencesAhvazIran Department of Biology Faculty of ScienceShahid Chamran University of AhvazAhvazIran Department of Immunology Faculty of MedicineAhvaz Jundishapur University of Medical SciencesAhvazIran

Objective:To investigate the relationship between ambient sulfur dioxide(SO2)exposure and semen quality ***:A systematic literature search was conducted to identify relevant studies investigating the association between SO2 exposure and semen quality *** search encompassed the timeframe from January 2000 to May 2023 and included electronic databases such as Web of Science,Google Scholar,PubMed,Cochrane,and *** effect estimates with 95%confidence intervals(CI)were calculated using percent changes(PC).The meta-analysis included seven studies with 6711 participants and 15087 semen ***:The results revealed a significant negative association between ambient SO2 exposure and certain semen quality *** particular,SO2 exposure was associated with a significant decrease in progressive motility(PC=0.032;95%CI:-0.063 to-0.001;P=0.044)and sperm concentration(PC=-0.020;95%CI:-0.036 to-0.005;P=0.012).However,no statistically significant associations were observed for total sperm count(PC=-0.038;95%CI:-0.079 to 0.003;P=0.070),seminal fluid volume(PC=-0.009;95%CI:-0.048 to-0.030;P=0.662)and sperm motility(PC=-0.17;95%CI:-0.363 to 0.022;P=0.830).In addition,the results of the subgroup analysis revealed specific variables that were associated with the decrease in relevant sperm ***:This systematic review and meta-analysis provides compelling evidence supporting a consistent negative association between exposure to ambient SO2 and semen quality parameters.

关键词： Semen quality Sulfur dioxide Ambient air pollution Meta-analysis

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Hepatoprotective effect of Holothuria leucospilota methanolic extract on dimethyl nitrosamine-induced hepatotoxicity in rats

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Animal Models and Experimental Medicine 2024年第4期7卷 544-552页

作者： Fatemeh Dejan Amineh Daneshi Javad Rajabi Aslani Nasrollah Ahmadi Narges Eskandari Roozbahani Elaham Rahmanian reza Behmanesh hamid reza Gheisari Department of Basic Sciences School of Veterinary MedicineShiraz UniversityShirazIran Department of Education Farzanegan High SchoolTehranKohgiluyeh and Boyer AhmadIran Food Hygiene Department School of Veterinary MedicineShiraz UniversityShirazIran Department of Pathology School of Veterinary MedicineShiraz UniversityShirazIran Clinical Research Development Center Imam Reza HospitalKermanshah University of Medical SciencesKermanshahIran Molecular Dermatology Research Center Shiraz University of Medical SciencesShirazIran Department of Anatomy School of MedicineShiraz University of Medical SciencesShirazIran Faculty of Veterinary Medicine Garmsar BranchDepartment of RadiologyIslamic Azad UniversityGarmsarIran

Background:Complementary medicine is an interesting field for extracting bio-active compounds from various plant and animal *** hepatoprotective effect of the methanolic extract of a species of sea cucumber called Holothuria leu-cospilota in an animal model of liver cancer caused by dimethyl nitrosamine(DMN)was ***:Wistar female rats were randomly divided into five groups(n=12):control(intact),positive control(received 1%DMN[10 mg/kg/week,intraperitoneally]for 12 weeks),and three treatment groups(received 50,100,and 200 mg/kg/day ***-cospilota extract orally for 12 weeks along with intraperitoneal administration of 1%DMN[10 mg/kg/week]).In all groups,ultrasound was performed on the liver every week to check its *** sampling and liver isolation were performed on three occasions,at 4,8,and 12 weeks,to check liver enzymes and the histopathological condition of the liver tissue(every week,four animals from each group were randomly selected).Results:Liver density changes were evident from the eighth week onward in the positive control *** results indicated pathologic changes in the positive control group after 4 *** increase in liver enzymes in the posi-tive control group was significantly different from that in the treatment and control ***:We demonstrated the hepatoprotective effect of *** on DMN-induced liver damage in rats using biochemical and histological parameters and *** additional research(in silico or in vitro)is needed to find the exact mechanism and the main biological compound in ***.

关键词： dimethyl nitrosamine hepatotoxicity Holothuria leucospilota sea cucumber

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Experimental and Finite Element Analysis of Corroded High-Pressure Pipeline Repaired by Laminated Composite

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Computer Modeling in Engineering & Sciences 2024年第8期140卷 1783-1806页

作者： Seyed Mohammad reza Abtahi Saeid Ansari Sadrabadi Gholam Hosein Rahimi Gaurav Singh hamid Abyar Daniele Amato Luigi Federico Faculty of Mechanical Engineering Tarbiat Modares UniversityTehran***Iran A.Leon Linton Department of Mechanical Robotics and Industrial EngineeringLawrence Technological UniversitySouthfieldMI48075USA Department of Mechanical Engineering Faculty of EngineeringMeybod UniversityYazd***Iran Department of Industrial Engineering University of SalernoVia Giovanni PaoloⅡFiscianoItaly Italian Aerospace Research Center(C.I.R.A.) Via MaioriseCapuaCE81043Italy

Repairs of corroded high-pressure pipelines are essential for fluids transportation under high *** of the methods used in their repairs is the use of layered *** composite used must have the necessary ***,the experiments and analytical solutions presented in this paper are performed according to the relevant standards and codes,including ASME PCC-2,ASME B31.8S,ASME B31.4,ISO 24817 and ASME *** addition,the experimental tests are replicated numerically using the finite element *** the strain gauges at different distances from the defect location,can reduce the nonlinear effects,deformation,and fluctuations due to the high *** direct relationship between the depth of an axial defect and the stress concentration is observed at the inner side edges of the *** reparation reduces the non-linearities related to the sharp variation of the geometry and a more reliable numerical simulation could be performed.

关键词： High-pressure pipeline composite repair ASME PCC-2 ISO 24817

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