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Mahdi Shabani

Shahid Beheshti University of Medical Sciences

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Mahmood Jeddi‐Tehrani

Academic Center for Education, Culture and Research

Hossein Asgarian‐Omran

Mazandaran University of Medical Sciences

Hodjatallah Rabbani

Karolinska University Hospital

Mohammad Hojjat‐Farsangi

Karolinska Institutet

Fazel Shokri

Tehran University of Medical Sciences

Fazel Shokri

Tehran University of Medical Sciences

Ramazan Ali Sharifian

Tehran University of Medical Sciences

Parvaneh Vossough

Mahak Hospital and Rehabilitation Complex

Fazel Shokri

Tehran University of Medical Sciences

Davoud Rostamzadeh

Yasuj University of Medical Sciences

Cooperative Institutions

Tehran University of Medical Sciences

Shahid Beheshti University of Medical Sciences

University of Tehran

Academic Center for Education, Culture and Research

Tabriz University of Medical Sciences

Shahid Beheshti University

Iran University of Medical Sciences

Pasteur Institute of Iran

Tarbiat Modares University

Shiraz University of Medical Sciences

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Expression profile of orphan receptor tyrosine kinase (ROR1) and Wilms' tumor gene 1 (WT1) in different subsets of B-cell acute lymphoblastic leukemia

Leukemia & lymphoma/Leukemia and lymphoma (2008)

Mahdi Shabani Hossein Asgarian‐Omran Parvaneh Vossough Ramazan Ali Sharifian Mohammad Faranoush

Recent molecular investigations have demonstrated over-expression of a large number of tumor associated antigens (TAAs) in a variety of malignancies. Over-expression of ROR1 gene, a member of the receptor tyrosine kinase family, has recently been reported in B-cell chronic lymphocytic leukemia. Wilms' tumor gene 1 (WT1) has long been known as a universal TAA expressed in a variety of solid and hematopoietic malignancies. In the present study, the expression profile of ROR1 and WT1 was investigated in different immunophenotypic subsets of B-cell acute lymphoblastic leukemia (B-ALL) patients. RT-PCR method was used to determine the ROR1 and WT1 genes expression in bone marrow (BM) and peripheral blood (PB) samples from 51 newly diagnosed Iranian B-ALL patients. Isolated tumor cells from all patients were immunophenotyped by flow cytometry. Based on immunophenotypic results, our B-ALL patients were classified in four differentiation subsets; Pro-B (n = 7), Pre-B I (n = 29), Pre-B II (n = 13) and Immature/mature B-ALL (n = 2). Although ROR1 was over-expressed in more mature subsets (16.7%, 42.9%, 45.5% and 100%, respectively), WT1 was more represented in immature subsets of B-ALL patients (57.1%, 64.3%, 38.5% and 0%, respectively). Comparison of the frequency of ROR1 and WT1 positive samples at each immunophenotypic subtype revealed statistically significant difference only in Pre B I subtype (p = 0.02). Our results suggest that expression of ROR1 and WT1 in B-ALL is associated with the differentiation stage of the leukemic cells.

ROR1

Immunophenotyping

10.1080/10428190802124000

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Citations (46)

Targeting Receptor Tyrosine Kinases Using Monoclonal Antibodies: The Most Specific Tools for Targeted-Based Cancer Therapy

Current Drug Targets (2015)

Mahdi Shabani Mohammad Hojjat‐Farsangi

Receptor tyrosine kinases (RTKs) family is comprised of different cell surface glycoproteins. These enzymes participate in and regulate vital processes such as cell proliferation, polarity, differentiation, cell to cell interactions, signaling, and cell survival. Dysregulation of RTKs contributes to the development of different types of tumors. RTKs deregulation in different types of cancer has been reported for more than 30 RTKs. Due to their critical roles, the specific targeting of RTKs in malignancies is a promising approach. Targeted cellular and molecular therapies (personalized medicine) have been known as new types of therapeutics, which prevent tumor cell proliferation and invasion by interfering with molecules essential for tumor growth and survival. Specific targeting of RTKs using monoclonal antibodies (mAbs) in malignancies as well as in autoimmune disorders is of great interest. The growing number of mAbs approved by the authorities implies on the increasing attentions and applications of these therapeutic tools. Due to the high specificity, mAbs are the most promising substances that target RTKs expressed on the tumor cell surface. In this communication, we review the recent progresses in the development of mAbs targeting oncogenic RTKs for cancer treatment.

Targeted Therapy

10.2174/1389450116666151001104133

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Optimization of Gene Transfection in Murine Myeloma Cell Lines using Different Transfection Reagents.

Mahdi Shabani Shayda Hemmati Reza Hadavi Zahra Amirghofran Mahmood Jeddi‐Tehrani

Purification and isolation of cellular target proteins for monoclonal antibody (MAb) production is a difficult and time-consuming process. Immunization of mice with murine cell lines stably transfected with genes coding for xenogenic target molecules is an alternative method for mouse immunization and MAb production. Here we present data on transfection efficiency of some commercial reagents used for transfection of murine myeloma cell lines. Little is known about transfectability of murine myeloma cell lines by different transfection reagents. Mouse myeloma cell lines (SP2/0, NS0, NS1, Ag8, and P3U1) were transfected with pEGFP-N1 vector using Lipofectamine 2000, jetPEI and LyoVec commercial transfection reagents in different combinations. The transfection permissible HEK293-FT cell line was used as a control in transfection procedure. Transfected cells, expressing the Enhanced Green Fluorescent Protein (EGFP), were analyzed by flow cytometry 48 hrs post transfection. Our results showed transfection efficiency of 71%, 57% and 22% for HEK293-FT, 5.5%, 3.4% and 1% for SP2/0, 55.7%, 21.1% and 9.3% for NS0, 8.2%, 6% and 5.5% for NS1, 22%, 49.2% and 5.5% for Ag8 and 6.3%, 21.5% and 4.6% for P3U1 cell lines after transfection with Lipofectamine 2000, jetPEI and LyoVec reagents, respectively. Our data indicate that NS0 and Ag8 are efficiently transfected by Lipofectamine 2000 and jetPEI reagents. Finally, we propose Ag8 and NS0 cell lines as suitable host cells for efficient expression of target genes which can be used for mouse immunization and MAb production.

Lipofectamine

HEK 293 cells

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5-Fluorouracil Effectively Depletes Tumor Induced Myeloid Derived Suppressor Cells in 4T1 Mammary Carcinoma Model

Avicenna Journal of Medical Biotechnology (2024)

Khadijeh Ramezani-Aliakbari Seyed Amir Jalali Maedeh Alinejad Mahmood Jeddi‐Tehrani Mahdi Shabani

Background: Myeloid Derived Suppressor Cells (MDSCs) are capable of inhibiting both innate and adaptive immune responses and accumulate in the microenvironment of breast tumors. Hence, MDSC depletion by chemotherapeutic agents can improve clinical efficacy of cancer immunotherapy. The effects of 5-FU and doxorubicin agents on MDSC reduction in 4T1 breast cancer murine model were evaluated. Methods: 5×105 of 4T1 tumor cells were injected into mammary fat pad of BALB/c female mice. Tumor bearing mice were randomly divided into 4 groups: PBS receiving control group, doxorubicin receiving groups at doses of 2.5 and 5 mg/kg, and 5-FU receiving group at dose of 50 mg/kg. Doxorubicin and 5-FU agents were intraperitoneally administrated at three doses with 5-day intervals and five doses for three times a week, respectively. Then, on day 20 post tumor cells injection, spleens and tumors were isolated to determine frequency of CD11b+ Gr1+ MDSCs by flow cytometry analysis. Results: 5-FU was able to reduce significantly both splenic and interatumoral MDSCs comparing to control group (p=0.0276 and p=0.0067, respectively). Also, Doxorubicin treatment at dose of 50 mg/kg was associated to a significant reduction of splenic MDSCs in comparison to untreated group (p=0.0382). However, only 5-FU injection led to inhibit notably tumor growth in comparison to control group (p=0.0139). Conclusion: Findings show that 5-FU has inhibitory effects on MDSCs and tumor growth in 4T1 tumor model. So, more investigations are needed to study combination of 5-FU with immune based approaches to enhance the efficacy of cancer therapies.

Myeloid-derived Suppressor Cell

Mammary tumor

Mammary carcinoma

Breast carcinoma

10.18502/ajmb.v16i4.16740

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Antibody Response to Human Extracellular HER2 Subdomain Proteins in Mice.

DOAJ (DOAJ: Directory of Open Access Journals) (2017)

Fateme Sadri-Ardalani Moslem Ahmadi Azam Hemmati Shaghayegh Emami Samira Farid

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.To investigate and characterize antibody responses to human recombinant proteins of HER2 extracellular subdomains in immunized mice.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.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.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.

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Citations (4)

Correlations and diagnostic tools for metabolic syndrome (MetS) and chronic obstructive pulmonary disease (COPD).

Mahshid Bahrami Khatereh Forouharnejad Hannaneh Mirgaloyebayat Nadia Ghasemi Darestani Mozhgan Ghadimi

Regarding the importance of obesity in patients with chronic obstructive pulmonary disease (COPD), we aimed to evaluate of correlation between metabolic syndrome (MetS) and COPD.In this cross-sectional study, 96 patients with COPD were evaluated. This study was conducted in 2016-2018. The severity of COPD was determined by Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 criteria. We investigated the correlations between MetS with COPD and possible diagnostic tools.Of all COPD patients, 86.5% had MetS, and the means of waist circumference, fasting blood glucose, systolic and diastolic blood pressure, body mass index, and triglyceride in patients with MetS were significantly higher than the patients without MetS (P < 0.05). We showed that forced expiratory volume in 1 second (FEV1) with a 37% cutoff had 92.8% and 69.2% sensitivity and specificity, respectively (area of the curve: 0.51, 0.31-0.71).MetS is prevalent among COPD and FEV1 could be considered as important diagnostic tool for COPD.

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Citations (3)

Proteome Analysis of Adult Acute Lymphoblastic Leukemia by Two-dimensional Blue Native/Sodium Dodecyl Sulfate Gel Electrophoresis

Avicenna Journal of Medical Biotechnology (2022)

Servin Bagheralmoosavi Parastou Gholami Mahdi Amini Mahdi Alizadeh Marjan Yaghmaei

Despite the significant progress in the treatment of Acute Lymphoblastic Leukemia (ALL) in children, it still remains as one of the most challenging malignancies in adults. Identification of new biomarkers may improve the management of adult ALL. Proteins expressed on the cell surface can be considered as disease-associated biomarkers with potential for diagnosis and targeted therapies. Thus, membrane proteome studies give essential information about the disease-related biomarkers.We applied 2-dimensional blue-native SDS-PAGE technique followed by MALDI-TOF/TOF-mass spectrometry to study the cell membrane proteome of peripheral blood mononuclear cells of adult B-ALL patients in comparison to that of the healthy controls.Sixty seven differentially expressed protein spots were detected, among them 52 proteins were found to be up-regulated but the other 15 proteins were down-regulated in B-ALL. Five differentially expressed proteins, involved in energy metabolism pathways, were detected in B-ALL patients compared to the healthy control group.Differentially expressed proteins provide an insight into the molecular biology of B-ALL. Further studies must be done to confirm our data to be considered as potential targets for detection and treatment of B-ALL.

Proteome

Sodium dodecyl sulfate

10.18502/ajmb.v15i1.11421

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Citations (1)

Expression of the testis-specific gene, TSGA10, in Iranian patients with acute lymphoblastic leukemia (ALL)

Leukemia Research (2006)

Maryam Beigom Mobasheri Mohammad Hossein Modarressi Mahdi Shabani Hossein Asgarian‐Omran Ramezanali Sharifian

Minimal Residual Disease

10.1016/j.leukres.2005.11.012

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Citations (38)

Cloning, expression and characterization of a peptibody to deplete myeloid derived suppressor cells in a murine mammary carcinoma model

Protein Expression and Purification (2022)

Khadijeh Ramezani-Ali Akbari Vahid Khaki-Bakhtiarvand Jafar Mahmoudian Hossein Asgarian‐Omran Fazel Shokri

Myeloid-derived Suppressor Cell

Lipofectamine

10.1016/j.pep.2022.106153

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Citations (2)

Investigation of Expression Profile of Placenta-specific 1 (PLAC1) in Acute Myeloid and Lymphoid Leukemias

Avicenna Journal of Medical Biotechnology (2023)

Parastou Gholami Hossein Asgarian‐Omran Marjan Yaghmaie Jafar Mahmudian Shirin Kianersi

Background: Placenta-specific 1 (PLAC1) is one of the cancer-testis-placenta antigens that has no expression in normal tissue except placenta trophoblast and testicular germ cells, but is overexpressed in a variety of solid tumors. There is a lack of studies on the expression of PLAC1 in leukemia. We investigated expression of PLAC1 in Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia (ALL). Methods: In this study, we investigated expression pattern of PLAC1 gene in peripheral blood and bone marrow mononuclear cells of newly-diagnosed patients with AML (n=31) and ALL (n=31) using quantitative real-time PCR. Normal subjects (n=17) were considered as control. The PLAC1 protein expression in the samples were also detected using western blotting. Results: Our data demonstrated that PLAC1 transcripts had 2.7 and 2.9 fold-change increase in AML and ALL, respectively, compared to normal samples. PLAC1 transcript expression was totally negative in all studied normal subjects. Level of PLAC1 mRNA expression in ALL statistically increased compared to normal samples (p=0.038). However, relative mRNA expression of PLAC1 in AML was not significant in comparison to normal subjects (p=0.848). Furthermore, relative mRNA expression of PLAC1 in AML subtypes was not statistically significant (p=0.756). PLAC1 gene expression showed no difference in demographical clinical and para-clinical parameters. Western blotting confirmed expression of PLAC1 in the ALL and AML samples. Conclusion: Considering PLAC1 expression profile in acute leukemia, PLAC1 could be a potential marker in leukemia which needs complementary studies in the future.

10.18502/ajmb.v15i3.12926

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Citations (2)