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کاربرد نوع شرط:
- جایگاه : پژوهشی
- مجله: Iranian Journal of Immunology
- نوع مقاله: Journal Article
- کلمات کلیدی:
- چکیده:
- چکیده انگلیسی:
- انتشار مقاله: 23-12-1397
- نویسندگان: Mohammad Mehdi Amiri,Tannaz Bahadori,Tahereh Soltantoyeh,Reza Hosseini-Ghatar,Forough Golsaz-Shirazi,Mahmood Jeddi-Tehrani,Fazel Shokri
- مشاهده
- جایگاه : پژوهشی
- مجله: Iranian Journal of Immunology
- نوع مقاله: Journal Article
- کلمات کلیدی: Breast cancer,HER2,Immunotherapy,Polyclonal antibody,subdomains of HER2
- چکیده:
- چکیده انگلیسی: Background: Human epidermal growth factor receptor 2 (HER2) has a crucial role in several malignancies. The extracellular domain of HER2 (HER2-ECD) has been extensively employed as an important target in passive and active immunotherapy. Isolated recombinant prokaryotic HER2-ECD subdomains were previously found to be ineffective in inducing anti-tumor antibody response. Objective: To employ recombinant eukaryotic HER2-ECD subdomains to raise anti-HER2 antibodies and determine their anti-tumor activity in vitro. Methods: Two paired subdomains of HER2-ECD (DI+II and DIII+IV), representing Pertuzumab and Trastuzumab binding domains, respectively, along with the full extracellular domain of HER2 were generated in CHO-K1 cells. Polyclonal antibodies were raised against these subdomains and characterized using ELISA, flow cytometry, and immunoblot and their anti-tumor activity was assessed by XTT assay. The cross-reactivity of these antibodies was specified along with other members of the human HER family. Results: Similar to Trastuzumab and anti-HER2-ECD antibody, anti-DI+II and DIII+IV polyclonal antibodies reacted with recombinant HER2-ECD and native HER2 expressed on tumor cells. These two polyclonal antibodies were able to inhibit the binding of Pertuzumab and Trastuzumab to HER2, respectively, and did not cross-react with other members of HER family. These antibodies were able to inhibit tumor cell growth in vitro, similar to Trastuzumab. Conclusion: The high immunogenicity of human HER2 DI+II and DIII+IV subdomains in rabbits and the tumor inhibitory activity of the purified specific antibodies imply that they might be suitable for active immunotherapy in formulation with appropriate adjuvants and in combination with other HER2 specific therapeutics.
- انتشار مقاله: 27-06-1396
- نویسندگان: Reza Hosseini-Ghatar,Tahereh Soltantoyeh,Motahareh Bahadori,Jalal Khoshnoodi,Forough Golsaz-Shirazi,Mahmood Jeddi-Tehrani,Mohammad Mehdi Amiri,Fazel Shokri
- مشاهده
- جایگاه : پژوهشی
- مجله: Iranian Journal of Immunology
- نوع مقاله: Journal Article
- کلمات کلیدی: Breast cancer,Recombinant protein,Immunization,HER2
- چکیده:
- چکیده انگلیسی: Background: In addition to passive immunotherapy using anti-HER2 monoclonal antibodies, active immunotherapy via HER2 targeting is an interesting approach to inducing specific anti-tumor immune responses. We have recently reported the immunogenicity of HER2 subdomains following DNA immunization and HER2 protein boosting. In the present study, we evaluated the immunogenicity of different HER2 extracellular subdomains for the induction of anti-HER2 antibody response in BALB/c mice. Objective: To investigate and characterize antibody responses to human recombinant proteins of HER2 extracellular subdomains in immunized mice. Methods: Four subdomains of HER2 extracellular domain were expressed in E.coli; subsequently, purified recombinant proteins were intraperitoneally injected in BALB/c mice with Freund's adjuvant. The anti-HER2 antibody response was detected by ELISA, immunoblotting and flow cytometry. Results: All the four HER2 subdomains along with the full extracellular domain (fECD) were able to induce specific anti-HER2 antibodies. Although anti-HER2 subdomains antibodies could not react with eukaryotic recombinant fECD protein by ELISA, they were able to recognize this protein by immunoblotting under both reduced and non-reduced conditions. Furthermore, only the sera of mice immunized with fECD protein could recognize native HER2 on HER2 overexpressing tumor cells (>99%) by flow cytometry. Moreover, fECD immunized mice sera inhibited the proliferation of tumor cells by XTT assay. Conclusion: The prokaryotic recombinant proteins of HER2 extracellular subdomains are immunogenic, yet the induced specific antibodies do not react with the native HER2 protein due to the paucity of post-translation modifications and /or distortion of the native conformation of isolated HER2 extracellular subdomains which might be potentially effective for induction of cell mediated immune response against HER2.
- انتشار مقاله: 30-03-1396
- نویسندگان: Fateme Sadri-Ardalani,Moslem Ahmadi,Azam Hemmati,Shaghayegh Emami,Samira Farid,Mohammad Mehdi Amiri,Mahmood Jeddi-Tehrani,Mahdi Shabani,Fazel Shokri
- مشاهده
- جایگاه : پژوهشی
- مجله: Iranian Journal of Immunology
- نوع مقاله: Journal Article
- کلمات کلیدی: Monoclonal antibody,"a" Determinant,HBs Ag
- چکیده:
- چکیده انگلیسی: Background: The antibody response to hepatitis B surface antigen (HBsAg) controls hepatitis B virus infection. The "a" determinant of HBsAg is the most important target for protective antibody response, diagnosis and immunoprophylaxis. Mutations in this area may induce immune escape mutants and affect the performance of HBsAg assays.
Objectives: To construct clinically relevant recombinant mutant forms of HBsAg and assessment of their reactivity with anti-HBs monoclonal antibodies (MAbs).
Methods: Wild type (wt) and mutant (mt) HBsAg genes were constructed by site directed mutagenesis and SEOing PCR. The amplified genes were inserted into pCMV6-neo plasmid and transfected in CHO cell line. The expression of wt- and mtHBsAg was assessed by commercial ELISA assays and stable cells were established and cloned by limiting dilution. The recombinant mutants were further characterized using a panel of anti-HBs monoclonal antibodies (MAbs) and the pattern of their reactivity was assessed by ELISA.
Results: Ten HBsAg mutants having single mutation within the "a" determinant including P120E, T123N, Q129H, M133L, K141E, P142S, D144A, G145R, N146S and C147S together with a wt form were successfully constructed and expressed in CHO cells. Reactivity of anti-HBs MAbs with mtHBsAgs displayed different patterns. The effect of mutations on antibody binding differed depending on the amino acid involved and its location within the ‘‘a’’ determinant. Mutation at amino acids 123 and 145 resulted in either complete loss or significant reduction of binding to all anti-HBs MAbs.
Conclusion: Our panel of mtHBsAgs is a valuable tool for assessment of the antibody response to HBV escape mutants and may have substantial implications in HBV immunological diagnostics.- انتشار مقاله: 15-05-1395
- نویسندگان: Forough Golsaz Shirazi,Mohammad Mehdi Amiri,Hamed Mohammadi,Ali Ahmad Bayat,Azam Roohi,Jalal Khoshnoodi,Amir Hassan Zarnani,Mahmood Jeddi-Tehrani,Gholam Ali Kardar,Fazel Shokri
- مشاهده
- جایگاه : پژوهشی
- مجله: Iranian Journal of Immunology
- نوع مقاله: Journal Article
- کلمات کلیدی: RT-PCR,Wnt,Acute Lymphoblastic Leukemia,Immunophenotype
- چکیده:
- چکیده انگلیسی: Background: Dysregulation of WNT signaling has been reported in many malignancies.
Objective: This study was conducted to investigate the expression pattern of 14 members of the WNT gene family in different immunophenotypic subtypes of ALL.
Methods: Semi-quantitative RT-PCR was performed on samples from 71 ALL patients and 36 age-matched healthy individuals. The ALL patients were categorized into BALL (76%), T-ALL (22.6%) and mixed lineage (1.4%) and the B-ALL cases were further classified into pro-B, pre-BI, pre-BII and immature/mature-B based on immunophenotypic results.
Results: Among the WNT genes, WNT-7B (p=0.026), WNT-9A (p=0.020) and WNT-16B (p=0.023) were significantly over-expressed, whereas WNT- 2B (p=0.033), WNT-5A (p=0.016), WNT-7A (p<0.0001) and WNT-10A (p<0.0001) were down-regulated in B-ALL. Among the T-ALL subtype, however, significant down-regulation of WNT-2B, WNT-5B, WNT-7A, WNT-10A and WNT-11 was evident. Comparison between B-ALL subtypes showed significant over-expression of WNT-7B, WNT-9A and WNT-5B in certain subtypes.
Conclusion: Our results suggest contribution of the WNT genes in leukemogenesis of ALL.- انتشار مقاله: 15-05-1395
- نویسندگان: Ali Memarian,Parvaneh Vosough,Hossein Asgarian-Omran,Mina Tabrizi,Mahdi Shabani,Fazel Shokri
- مشاهده
- جایگاه : پژوهشی
- مجله: Iranian Journal of Immunology
- نوع مقاله: Journal Article
- کلمات کلیدی: Peripheral blood mononuclear cells,atherosclerosis,Cytotoxicity,oxLDL
- چکیده:
- چکیده انگلیسی: Background: Atherosclerosis, a chronic inflammatory disease of the vessel wall is characterized by local and systemic immune responses to a variety of antigens. Oxidized low-density lipoprotein (oxLDL) is considered as an important determining factor in the pathogenesis of atherosclerosis.
Objective: The purpose of this study was to investigate the degree of peripheral blood mononuclear cells (PBMC) vulnerability to in vitro oxLDL-induced cytotoxicity from atherosclerotic patients in comparison to healthy individuals.
Methods: Thirty patients with atherosclerotic lesions, confirmed by angiography, and 30 matched healthy individuals were investigated. PBMC was prepared from individuals' blood samples which were further stimulated with low dose (1 μg/mL) and high dose (50 μg/mL) of extensively oxidized LDL. MTT assay was utilized to measure cell viability and proliferation. Stimulation index (SI) was calculated as mean ratio of optical density (OD) of the stimulated cells divided by OD of untreated cells.
Results: Low dose oxLDL treatment caused no significant proliferative or cytotoxic effect in the control group; however, similar treatment caused significant cytotoxic effect in the patient group compared to the controls (p=0.026). High dose oxLDL treatment induced more significant cytotoxicity in the patient compared to the control group (p=0.006). Comparison of the SI between the two groups of patients and controls showed significantly lower index by either the low (p=0.03) or the high dose (p<0.001) oxLDL in the patients compared to the controls.
Conclusions: PBMC from patients with atherosclerosis showed increased susceptibility to oxLDL-induced cytotoxicity. Our results imply that prolonged exposure to elevated levels of circulating oxLDL could weaken the cellular defense mechanisms by progressive depletion of the pool of antiapoptotic proteins, rendering the cells more vulnerable to oxLDL-induced cell death.- انتشار مقاله: 15-05-1395
- نویسندگان: Mohammad Jafar Mahmoudi,Maryam Mahmoudi,Fereydoon Siassi,Fazel Shokri,Mohammad Reza Eshraghian,Amir Hassan Zamani,Reza Chahardoli,Mona Hedayat,Jalal Khoshnoodi,Hashem Nayeri,Nima Rezaei,Ali-Akbar Saboor-Yaraghi
- مشاهده
- جایگاه : پژوهشی
- مجله: Iranian Journal of Immunology
- نوع مقاله: Journal Article
- کلمات کلیدی: Anti-D immunoglobulin,D antigen,Hemolytic Disease of the Newborn (HDN),Monoclonal anti-D,Rh Blood Group System
- چکیده:
- چکیده انگلیسی: RhD antigen is the most immunogenic and clinically significant antigen of red blood cells after ABO system. It has historically been associated with hemolytic disease of the newborn (HDN) which is now routinely prevented by the administration of polyclonal anti-D immunoglobulin. This management of HDN has proven to be one of the most successful cases of prophylactic treatment based on antibody mediated immune sup-pression (AMIS). Despite the increasing efficiency of treatment, the mechanism of ac-tion of anti-D is not completely defined. There is a widespread interest in obtaining a reliable therapeutic monoclonal anti-D, due to difficulty of maintaining a pool of high titer volunteer donors for plasma collection and also increasing demand for antenatal prophylaxis and safety issues with plasma derived products. Candidate monoclonal anti-D preparations should demonstrate appropriate functionality in both in vitro and in vivo assays comparable to polyclonal anti-D immunoglobulin. These criteria are reviewed in addition to the factors regulating development of D specific immune response in D negative individuals and its suppression in HDN prophylaxis.
- انتشار مقاله: 17-05-1395
- نویسندگان: Roya Payam Khaja Pasha,Fazel Shokri
- مشاهده
- جایگاه : پژوهشی
- مجله: Iranian Journal of Immunology
- نوع مقاله: Journal Article
- کلمات کلیدی: Vaccination,Haplotype,Iranian,Hepatitis B virus,Allele,Human leukocyte antigen
- چکیده:
- چکیده انگلیسی: Background: Different studies have demonstrated that a small proportion of healthy individuals receiving the hepatitis B (HB) vaccine do not produce protective levels of anti-HB antibody, a phenomenon which could be linked to certain human leukocyte an-tigen (HLA) class-II alleles or haplotypes.
Objectives: The present study was under-taken to determine the frequency of HLA class-II alleles in Iranian healthy adult re-sponders and non-responders to HB vaccine.
Methods: Twelve non-responders (anti-HBs antibody<10 IU/L) and 46 responders (anti-HBs antibody>100 IU/L) were tissue typed for HLA class-II. HLA-DRB1, DQB1 and DQA1 alleles were determined using polymerase chain reaction based on sequence specific primers (PCR-SSP) technique. Accessibility to excess amount of genomic DNA was possible using Epstein-Barr virus (EBV)-transformed B-cells established from all vaccinees.
Results: Our results demon-strated increased frequencies of HLA- DRB1*07, DRB1*03, DRB1*04, DQB1*0201, DQA1*0201 alleles and HLA- DRB1*07/DQB1*0201/DQA1*0201 and DRB1*04/DQB1*0302/DQA1*03011 haplotypes in the non-responder group. Com-parison between responders and non-responders revealed only a significant difference for DQB1*0201 allele (p<0.05).
Conclusion: These findings confirm the association of certain HLA alleles and haplotypes with the lack of antibody response to HB vaccine in an Iranian population.- انتشار مقاله: 16-05-1395
- نویسندگان: Ali Akbar Amirzargar,Nilufar Mohseni,Mohammad Ali Shokrgozar,Zohreh Arjang,Nahid Ahmadi,Manijeh Yousefi Behzadi,Amir Amanzadeh,Fazel Shokri
- مشاهده
- جایگاه : پژوهشی
- مجله: Iranian Journal of Immunology
- نوع مقاله: Journal Article
- کلمات کلیدی: Progressive,Immunophenotyping,B-CLL,Indolent,CD38
- چکیده:
- چکیده انگلیسی: Background: Patients with B-cell chronic lymphocytic leukemia (B-CLL) have hetero-geneous clinical courses, thus several biological parameters need to be added to the cur-rent clinical staging systems to predict disease outcome. Recent immunophenotypic stud-ies performed mainly in Western populations have demonstrated the prognostic value of CD38 and ZAP-70 expression in B-CLL.
Objectives: To investigate the expression pat-tern of a variety of membrane antigens on leukemic cells from Iranian patients with CLL and to find out if there are any differences in the expression of these markers between in-dolent and progressive groups.
Methods: In the present study, peripheral blood samples from 87 Iranian patients with B-CLL were analysed by flow cytometry.
Results: In all cases, the neoplastic cells displayed B-CLL phenotype (CD5+/CD19+/sIg+). The vast ma-jority of the cases expressed CD23, but failed to stain for CD3 or CD14. The leukemic cells of most patients expressed CD27 (84/87, 95.4%) and CD45RO (74/87, 83.9%) molecules, suggesting a memory B-cell phenotype. Comparison between the indolent (n=42) and progressive (n=37) patients revealed significantly higher frequency and inten-sity of CD38 expression in progressive group (40.5%) compared to indolent (11.9%) pa-tients (p<0.05). None of the other membrane antigens were differentially expressed in these two groups of patients.
Conclusion: Our results obtained in an Asian ethnic popula-tion confirm and extend previous findings obtained from Western populations regarding the association of CD38 expression and disease progression in B-CLL.- انتشار مقاله: 16-05-1395
- نویسندگان: Mohammad Hojjat Farasangi,Mahmood Jeddi-Tehrani,Seyed Mohsen Razavi,Ramazan Ali Sharifian,Ahmad Shamsian Khoramabadi,Hojatollah Rabbani,Fazel Shokri
- مشاهده
- جایگاه : پژوهشی
- مجله: Iranian Journal of Immunology
- نوع مقاله: Journal Article
- کلمات کلیدی: RT-PCR,Wnt,β-catenin,Acute Myeloblastic Leukemia
- چکیده:
- چکیده انگلیسی: Background: Wnt molecules play a key role in growth, proliferation and development of some embryonic and adult organs as well as hematopoietic stem cells. Wnt signaling pathways are aberrantly activated in many tumor types, including solid tumors and hematologic malignancies.
Objective: To investigate the expression profile of a large number of Wnt genes in leukemic cells from Iranian patients with acute myeloblastic leukemia.
Methods: RT-PCR method was used to determine the Wnt genes expression in bone marrow (BM) and/or peripheral blood (PB) samples from 16 patients with AML and PB samples of 36 normal subjects.
Results: Among 14 Wnt molecules included in this study, Wnt-7A and Wnt-10A were significantly down-regulated (p = 0.002 and p < 0.0001, respectively) and Wnt-3 was significantly over-expressed (p < 0.02) in AML patients compared to normal subjects. No significant association was found between Wnt expression and FAB classification of the patients.
Conclusion: Our results demonstrated for the first time aberrant expression of Wnt-7A, Wnt-10A and Wnt-3 genes in Iranian AML patients. This may be of relevance to the tumorigenesis process in this malignancy.- انتشار مقاله: 17-05-1395
- نویسندگان: Ali Memarian,Mahmood Jeddi Tehrani,Parvaneh Vossough,Ramazan Ali Sharifian,Hodjatallah Rabbani,Fazel Shokri
- مشاهده