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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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Enhanced liver X receptor signalling reduces brain injury and promotes tissue regeneration following experimental intracerebral haemorrhage:roles of microglia/macrophages

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Stroke & Vascular Neurology 2023年第6期8卷 486-502,I0073-I0080页

作者： Ruiyi Zhang Yifei Dong Yang Liu Dorsa Moezzi Samira Ghorbani reza mirzaei Brian M Lozinski Jeff F Dunn V Wee Yong Mengzhou Xue Department of Cerebrovascular Diseases The Second Affiliated Hospital of Zhengzhou UniversityZhengzhouHenanChina Academy of Medical Science Zhengzhou UniversityZhengzhouHenanChina Hotchkiss Brain Institute and Department of Clinical Neurosciences University of CalgaryCalgaryAlbertaCanada Department of Biochemistry Microbiology&ImmunologyCollege of MedicineUniversity of SaskatchewanSaskatoonSaskatchewanCanada Department of Radiology University of CalgaryCalgaryAlbertaCanada

background Inflammation-exacerbated secondary brain injury and limited tissue regeneration are barriers to favourable prognosis after intracerebral haemorrhage(ICH).As a regulator of inflammation and lipid metabolism,Liver X receptor(LXR)has the potential to alter microglia/macrophage(M/M)phenotype,and assist tissue repair by promoting cholesterol efflux and recycling from *** support potential clinical translation,the benefits of enhanced LXR signalling are examined in experimental *** Collagenase-induced ICH mice were treated with the LXR agonist GW3965 or *** tests were conducted at multiple time *** and haematoma volume,and other brain parameters were assessed using multimodal MRI with T2-weighted,diffusion tensor imaging and dynamic contrast-enhanced MRI *** fixed brain cryosections were stained and confocal microscopy was applied to detect LXR downstream genes,M/M phenotype,lipid/cholesterol-laden phagocytes,oligodendrocyte lineage cells and neural stem *** blot and real-time qPCR were also ***3CR1^(CreER):Rosa26^(iDTR) mice were employed for M/M-depletion *** GW3965 treatment reduced lesion volume and white matter injury,and promoted haematoma *** mice upregulated LXR downstream genes including ABCA1 and Apolipoprotein E,and had reduced density of M/M that apparently shifted from proinflammatory interleukin-1β+to Arginase1+CD206+regulatory *** cholesterol crystal or myelin debris-laden phagocytes were observed in GW3965 *** activation increased the number of Olig2+PDGFRα+precursors and Olig2+CC1+mature oligodendrocytes in perihaematomal regions,and elevated SOX2+or nestin+neural stem cells in lesion and subventricular *** results supported better lesion recovery by GW3965,and this was corroborated by return to pre-ICH values of functional rotarod *** therapeutic effects of GW3965 were abrogated by M/M depletion in CX3CR1^(CreER):Ros

关键词： metabolism injury depletion

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Trigonella foenum-graecum seed extract modulates expression of lipid metabolism-related genes in HepG2 cells

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Asian Pacific Journal of Tropical Biomedicine 2019年第6期9卷 240-248页

作者： Maryam Mohammad-Sadeghipour Mehdi Mahmoodi Soudeh Khanamani Falahati-pour Alireza Khoshdel Mohammad Ali Fahmidehkar Mohammad reza mirzaei Mojgan Noroozi Karimabad Mohammad rezaHajizadeh Department of Clinical Biochemistry Faculty of MedicineRafsanjan University of Medical SciencesRafsanjanIran Molecular Medicine Research Center Inistitute of Basic Medical Sciences ResearchRafsanjan University of Medical SciencesRafsanjanIran Department of Clinical Biochemistry Afzalipoor Faculty of MedicineKerman University of Medical SciencesKermanIran Pistachio Safety Research Center Rafsanjan University of Medical SciencesRafsanjanIran Department of Clinical Biochemistry Faculty of Medicineand Pistachio Safety Research CenterRafsanjan University of Medical SciencesRafsanjanIran Department of Laboratory Sciences School of Paramedical SciencesTorbat Heydariyeh University of Medical SciencesTorbat HeydariyehIran

Objective:To investigate anti-dyslipidemic effects of hydroalcoholic fenugreek seed extracts,diosgenin,and 4-OH-Ile on HepG2 cell ***:HepG2 cells were treated with hydroalcoholic fenugreek seed extracts,diosgenin,4-OH-Ile,and ***20 was calculated using the MTT *** cells were then pretreated with IC20 concentrations for 24 and 48 *** time PCR was employed to measure expression of liver X receptor alpha(LXR a),sterol regulatory element-binding protein-1 C(SREBP-1 C),acetyl-CoA carboxylase(ACC),fatty acid synthase(FAS),fibroblast growth factor 21(FGF21),peroxisome proliferator-activated receptor gamma(PPAR γ),and lowdensity lipoprotein receptor(LDLR).Results:The results showed that LXR α(P=0.003,P<0.001).,SREBP-1 C(P<0.001,P<0.001),ACC(P=0.002,P=0.006),and FAS(P<0.001,P<0.001)were downregulated significantly,while FGF21(P<0.001,P<0.001),PPAR γ(P=0.004,P<0.001),and LDLR(P<0.001,P<0.001)were upregulated significantly in HepG2 cells treated with the IC20 of hydroalcoholic fenugreek seed extracts,diosgenin,4-OH-Ile,and orlistat in 24 and 48 h,***:Hydroalcoholic fenugreek seed extracts,diosgenin,and 4-OH-Ile significantly modulate the expression of some important lipid metabolism related genes,which is similar to *** foenum.-graecum seed extract or its derivatives should be further investigated for their dyslipidemia effects and its complications.

关键词： Fenugreek seed extract Diosgenin 4-Hydroxy-L-isoleucine Dyslipidemia Obesity

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Changes in climatic conditions drive variations in arbuscular mycorrhizal fungi diversity and composition in semi-arid oak forests

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Journal of Forestry Research 2024年第5期35卷 106-119页

作者： Nahid Jafarian Javad mirzaei reza Omidipour Yahya Kooch Department of Forest Science Faculty of AgricultureIlam UniversityIlam 69315-516Iran Department of Range and Watershed Management Faculty of AgricultureIlam UniversityIlam 69315-516Iran Faculty of Natural Resources and Marine Sciences Tarbiat Modares UniversityNoor 46417-76489MazandaranIran

Arbuscular mycorrhizal fungi(AMF)play a vital role in plant productivity and ecosystem ***,their responses to abiotic factors(i.e.,climate,physiography,and soil properties)are unknown,especially across climatic gradients and slope aspects in arid and semi-arid *** this study,using 60 composite soil samples,direct and indirect effects of climate factors and slope aspects on AMF diversity,composition and spore density were *** findings indicate that climate has a more direct influ-ence on soil properties(P<0.001)in comparison to slope aspect(P=0.449).In contrast,climate significantly affected AMF diversity and composition,with the highest diversity in dryer *** pH had the highest correlation with different facets of AMF *** equation modeling(SEM)indicated that only a small part of the variation in AMF diversity and spore density could be explained by climate characteristics,slope aspect and soil *** on SEM results,climate was the most important determinant of AMF diversity and spore density;slope aspect had a less critical *** outputs suggest that variations in AMF diversity are derived by the direct effects of climate and the indirect effect of soil chemical *** addition,with increasing dryness,sporulation and AMF diversity increased.

关键词： AMF diversity and composition Physiographic factors Semi-arid ecosystems Zagros forest

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Effects of preparation and operation conditions on precipitated iron nickel catalysts for Fischer-Tropsch synthesis

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Journal of Natural Gas Chemistry 2010年第3期19卷 341-353页

作者： Mostafa Feyzi Ali Akbar mirzaei Hamid reza Bozorgzadeh Department of Chemistry Faculty of SciencesUniversity of Sistan & Baluchestan Research Institute of Petroleum Industry(RIPI) Gas Division

Iron nickel oxide catalysts were prepared using co-precipitation procedure and studied for the conversion of synthesis gas to light *** particular,the effects of a range of preparation variables such as Fe/Ni molar ratios of the precipitation solution,precipitate aging times,calcination conditions,different supports and loading of optimum support on the structure of catalysts and their catalytic performance for the tested reaction were *** was found that the catalyst containing 40%Fe/60%Ni/40wt%Al 2O3 ,which was aged for 180 min and calcined at 600 ℃ for 6 h was the optimum modified *** catalytic performance of optimal catalyst has been studied in different operation conditions such as reaction temperatures,H2 /CO molar feed ratios and reaction total *** of both precursors and calcined catalysts was carried out by powder X-ray diffraction（XRD）,scanning electron microscopy（SEM）,Brunauer-Emmett-Teller（BET） surface area measurements,thermal analysis methods such as thermal gravimetric analysis（TGA） and differential scanning calorimetry（DSC）.

关键词： iron nickel light olefins Fischer-Tropsch operation conditions

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Sand mining disturbances and their effects on the diversity of arbuscular mycorrhizal fungi in a riparian forest of Iran

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Journal of Arid Land 2017年第6期9卷 837-849页

作者： Sareh MORADI BEHBAHANI Mostafa MORADI reza BASIRI Javad mirzaei Department of Forestry Faculty of Natural Resources and Environment B ehbahan Khatam A1-Anbia University of Technology Behbahan *** Iran Department of Forest Science Faculty of Agriculture Ilam University Ilam 69315516 Iran

The major objective of this study was to evaluate the effects of sand mining disturbances on the diversity of arbuscular mycorrhizal fungi（AMF）. In addition, the proportional changes in the diversity of AMF to the distances from riverbanks were assessed. For this purpose, the riparian forest of the Maroon River, Iran was divided into three locations with a 200-meter wide zone in between. Thus, the locations studied were named Distance I（riverbank）, Distance II（intermediate）, and Distance III（farthest from riverbank）. In each of these distances, 10 Tamarix arceuthoides and Populus euphratica of each species were randomly selected. At the same time, soil and root samples were collected from the rhizosphere of the tree species studied. Results indicated that totally 13 AMF species were observed in T. arceuthoides and 19 AMF species were recorded in P. euphratica rhizosphere belonging to 6 genera and 6 families. In these AMF species, Glomus segmentatum, G. geosporum, G. rubiforme, G. nanolumen, G. spinuliferum, Claroideoglomus drummondii, Gigaspora gigantea and Acaulospora paulinae appeared only in P. euphratica rhizosphere, while G. multiforum and Claroideoglomus claroideum were observed only in T. arceuthoides rhizosphere. Moreover, Distance II had the least AMF species both in T. arceuthoides and in P. euphratica rhizospheres, and also the least spore density and root colonization rate. Our results are important in that they provide a list of resistant AMF species that could be used in the conservation of biodiversity.

关键词： arbuscular mycorrhizal disturbance riparian forest sand mining Maroon River

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A new framework for selection of representative samples for special core analysis

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Petroleum Research 2020年第3期5卷 210-226页

作者： Abouzar mirzaei-Paiaman Seyed reza Asadolahpour Hadi Saboorian-Jooybari Zhangxin Chen Mehdi Ostadhassan National Iranian South Oil Company(NISOC) Department of Petroleum EngineeringAhvazIran Now at State University of Campinas(UNICAMP) CampinasSPBrazil Department of Chemical and Petroleum Engineering Schulich School of EngineeringUniversity of CalgaryCanada Key Laboratory of Continental Shale Hydrocarbon Accumulation and Efficient Development Ministry of EducationNortheast Petroleum University

Special core analysis(SCAL)measurements play a noteworthy role in reservoir *** to the time-consuming and costly character of these measurements,routine core analysis(RCAL)data should be inspected thoroughly to select a representative subset of samples for *** are no comprehensive guidelines on how representative samples should be *** this study,a new framework is presented for selection of representative samples for *** foundation of this framework is using methods of PSRTI,FZI*(FZI-star)and TEM-function for the early estimation of petrophysical static,dynamic,and pseudo-static rock types at RCAL *** global hydraulic element(GHE)approach is benefitted and a FZI*-based GHE method(i.e.,GHE*)is presented for partitioning *** framework takes into consideration different laboratory,reservoir engineering,geological,petrophysical and statistical factors.A carbonate reservoir case is presented to support our *** also show that the current forms of Lorenz and Stratigraphic Modified Lorenz Plots in reservoir engineering are not appropriate,and present new forms of them.

关键词： RCAL SCAL Sample selection Rock typing TEM-Function

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