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Middle East Journal of Digestive Diseases. 2018; 10 (3): 160-168
in English | IMEMR | ID: emr-199636


Background:Colorectal cancer [CRC] is one of the most common cancers worldwide. Recently treatments of advanced CRC have been immensely improved. In this study we reported the current state of advanced CRC in Iran regarding treatment and outcomes from 2000 to 2016

Methods:370 subjects with stage III or IV of the disease were included in this study. Pathological subtypes other than adenocarcinoma were excluded. Demographics and other relevant clinical data were collected

Results: Mean age at diagnosis was 55.4 ± 12.6 years. Significant differences regarding the age, sex, primary tumor complication and location, lymph node involvement, and tumor size were not detected between patients with stage III and IV. Overall survival rate at 5 years was 69.5% [95% confidence interval: 60.8% - 76.6%] and 21.73% [95% CI: 12.46% - 32.70%] for patients with stage III and IV, respectively. Analysis of prognostic factors revealed that tumor grade was an independent factor predicting poorer outcome [poorly differentiated vs. well or moderately differentiated]. Furthermore, in stage IV of the disease, IVb subgroup was found to be associated with a poorer outcome compared with stage IVa

Conclusion:Even with the acceptable survival rates and more effective treatments, it seems that clinico-pathological characteristics have yet the most important prognostic effect in advanced CRC

Cell Journal [Yakhteh]. 2018; 20 (2): 204-210
in English | IMEMR | ID: emr-198731


Objective: Chromosomal translocations are among the most common mutational events in cancer development, especially in hematologic malignancies. However, the precise molecular mechanism of these events is still not clear. It has been recently shown that alternative non-homologous end-joining [alt-NHEJ], a newly described pathway for double-stranded DNA break repair, mediates the formation of chromosomal translocations. Here, we examined the expression levels of the main components of alt-NHEJ [PARP1 and LIG3] in acute myeloid leukemia [AML] patients and assessed their potential correlation with the formation of chromosomal translocations

Materials and Methods: This experimental study used reverse transcription-quantitative polymerase chain reaction [RT- qPCR] to quantify the expression levels of PARP1 and LIG3 at the transcript level in AML patients [n=78] and healthy individuals [n=19]

Results: PARP1 was the only gene overexpressed in the AML group when compared with healthy individuals [P=0.0004], especially in the poor prognosis sub-group. Both genes were, however, found to be up-regulated in AML patients with chromosomal translocations [P=0.04 and 0.0004 respectively]. Moreover, patients with one isolated translocation showed an over-expression of only LIG3 [P=0.005], whereas those with two or more translocations over-expressed both LIG3 [P=0.002] and PARP1 [P=0.02]

Conclusion: The significant correlations observed between PARP1 and LIG3 expression and the rate of chromosomal translocations in AML patients provides a molecular context for further studies to investigate the causality of this association

Blood Research ; : 320-324, 2018.
Article in English | WPRIM | ID: wpr-718477


BACKGROUND: Recent studies have devoted much attention to non-protein-coding transcripts in relation to a wide range of malignancies. MALAT1, a long non-coding RNA, has been reported to be associated with cancer progression and prognosis. Thus, we here determined MALAT1 gene expression in chronic lymphocytic leukemia (CLL), a genetically heterogeneous disease, and explored its possible relationships with cytogenetic abnormalities. METHODS: MALAT1 expression level was evaluated using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) on blood mononuclear cells from 30 non-treated CLL patients and 30 matched healthy controls. Cytogenetic abnormalities were determined in patients by fluorescence in situ hybridization (FISH). RESULTS: MALAT1 expression level was up-regulated in the CLL group compared to healthy controls (P=0.008). Del13q14, followed by Del11q22, were the most prevalent cytogenetic abnormalities. We found no association between the FISH results and MALAT1 expression in patients. CONCLUSION: Altered expression of MALAT1 is associated with CLL development. Further investigations are required to assess the relationship between this long non-coding RNA and CLL patient survival and prognosis.

Humans , Chromosome Aberrations , Cytogenetics , Fluorescence , Gene Expression , In Situ Hybridization , Leukemia, Lymphocytic, Chronic, B-Cell , Polymerase Chain Reaction , Prognosis , Reverse Transcription , RNA, Long Noncoding
Archives of Iranian Medicine. 2013; 16 (2): 88-92
in English | IMEMR | ID: emr-140306


Thalassemia major and its treatment by stem cell transplantation can have deleterious effects on bone integrity. This study assesses the adverse effects of transplantation on growing bones of pediatric thalassemic patients. Bone mineral density [BMD] of 20 patients from three thalassemia classes whose mean [SD] age was 7.4 [3.8] years were tested with a Norland XR-46 device at baseline [before transplantation], 6 and 12 months after transplantation. At 6 and 12 months after transplantation we observed no significant changes in mean BMD. There were no Z-scores less than -2 among patients. Class 3 thalassemia did not negatively impact BMD. Calcium [Ca], phosphorous [P] and ferritin levels were not significantly related to patients' BMD scores. Transfusion duration and chelation therapy showed positive significant relationships to BMD [g/ cm2], but no significant relation with the BMD Z-score. The deleterious relation between corticosteroid use and changes in BMD was not significant. In contrast, patients who developed acute graft versus host disease [aGVHD] after transplantation showed significant adverse effects on BMD of their femur [P = 0.020] and spine [P = 0.027]. Stem cell transplantation in pediatric thalassemic patients who do not develop aGVHD does not appear to have any significant positive or negative effects on BMD

Humans , Male , Female , beta-Thalassemia , Hematopoietic Stem Cell Transplantation/adverse effects , Pediatrics , Graft vs Host Disease
Acta Medica Iranica. 2013; 51 (5): 284-288
in English | IMEMR | ID: emr-161108


Dendritic cells [DCs] are professional antigen presenting cells that have a potential role in the initiating of immune responses. The cell vaccination is a new strategy in treatment of infectious diseases and cancers. In this study, we have generated monocyte-derived dendritic cells of lymphoma patient's peripheral blood mononuclear cells then; these cells were used as vaccine in lymphoma patients. We generated dendritic cell vaccine from lymphoma patient's blood monocytes with human interleukin-4, granulocyte monocyte colony stimulating factor and then, antigen-primed DCS were administrated subcutaneously close to the inguinal lymph nodes after maturation of dendritic cells. After 7 days, we analyzed immune response in lymphoma patients with determining of LDH, Beta 2 Microglobulin, CD4+T cell percent, CD8+ Tcell percent and Tumor size before and after vaccination. Furthermore, phenotypic and functional analysis of dendritic cells was performed using anti CD83-FITC monoclonal antibodies. Before vaccination, the mean +/- SD of LDH was 530.62 +/- 140.65 but after vaccination it was 459 +/- 109.45 that significantly different between experimental groups [P=0.002]. In addition, the CD8+ T cells percentage significantly different between two groups [MX002]. We concluded that the use of dendritic cell probably is one of the suitable noninvasive treatments for lymphoma patients that they have not response to chemical drugs

Cell Journal [Yakhteh]. 2012; 13 (4): 251-258
in English | IMEMR | ID: emr-178458


microRNAs [miRNAs] are a new class of non-coding RNAs involved in regulating various biological processes including proliferation, differentiation, and apoptosis, among others. Alterations in miRNA expression are reported in several human cancers, which suggests their potential roles in tumor initiation and progression. Members of the miR-302 cluster are highly expressed in embryonic stem cells [ESC], where they regulate cell self-renewal and pluripotency. Based on the cancer stem cell [CSC] hypothesis, mis-expression of such genes might contribute to tumorigenicity. This study aims to find a potential link between the expression level of human/homo sapiens miR-302b [has-miR- 302b] and tumor/grade state of gastric tissues. A matched based case-control study was conducted that included tumor and matched marginal non-tumor surgical specimens from 34 patients diagnosed with gastric adenocarcinoma. Randomly selected samples were obtained from the Iran National Tumor Bank. cDNA synthesis was carried out on total RNA, by using the miRCURY LNA[Trade Mark sign]Universal RT microRNA PCR Kit. Real-time reverse transcriptionpolymerase chain reaction [RT-PCR] assays were performed with specific LNA[Trade Mark sign] primers and SYBR Green master mix. The human embryonic carcinoma cell line, NTERA2 [NT2] and a human gastric adenocarcinoma cell line, AGS, were used to optimize the PCR reactions. A comparative evaluation of miR-302b expression in tumor and non-tumor gastric samples was performed by either paired t test or Wilcoxon non-parametric test. The ability of miR-302b to discriminate tumor from non-tumor gastric samples was evaluated using the area under the receiver operating characteristic [ROC] curve. According to our data, miR-302b expression [normalized to that of the U6 snRNA housekeeping gene] in the pluripotent cell line NT2 was more than 500 times greater than that of the AGS cell line. The level of expression was even lower in tumor and non-tumor gastric tissue samples. The data further revealed a down-regulation of miR-302b in gastric tumor samples [p=0.001], particularly in high-grade adenocarcinoma [p=0.009]. However, ROC analysis data demonstrated a low sensitivity and specificity of miR-302b expression to discriminate between the tumor and non-tumor state of the samples [AUC=0.63]. Despite the upregulation of some hESC-specific genes in tumors, our data revealed a down-regulation of miR-302b in high-grade tumors. This data suggested a potential tumor-suppressor role for miR-302b in tumorigenesis of gastric tissue

Humans , Female , Male , Stomach Neoplasms , MicroRNAs , Neoplastic Stem Cells , Cell Line , Down-Regulation
Acta Medica Iranica. 2012; 50 (2): 79-96
in English | IMEMR | ID: emr-163579


Stem cells are undifferentiated cells with the ability of proliferation, regeneration, conversion to differentiated cells and producing various tissues. Stem cells are divided into two categories of embryonic and adult. In another categorization stem cells are divided to Totipotent, Multipotent and Unipotent cells. So far usage of stem cells in treatment of various blood diseases has been studied [such as lymphoblastic leukemia, myeloid leukemia, thalassemia, multiple myeloma and cycle cell anemia]. In this paper the goal is evaluation of cell therapy in treatment of Parkinson's disease, Amyotrophic lateral sclerosis, Alzheimer, Stroke, Spinal Cord Injury, Multiple Sclerosis, Radiation Induced Intestinal Injury, Inflammatory Bowel Disease, Liver Disease, Duchenne Muscular Dystrophy, Diabetes, Heart Disease, Bone Disease, Renal Disease, Chronic Wounds, Graft-Versus-Host Disease, Sepsis and Respiratory diseases. It should be mentioned that some disease that are the target of cell therapy are discussed in this article

Humans , Animals , Pluripotent Stem Cells , Totipotent Stem Cells , Hematologic Diseases/therapy , Nervous System Diseases/therapy , Therapeutics , Bone Diseases/therapy
IBJ-Iranian Biomedical Journal. 2012; 16 (1): 10-17
in English | IMEMR | ID: emr-124805


The secondary genetic changes other than the promyelocytic leukemia-retinoic acid receptor [PML-RARA] fusion gene may contribute to the acute promyelocytic leukemogenesis. Chromosomal alterations and mutation of FLT3 [FMS-like tyrosine kinase 3] tyrosine kinase receptor are the frequent genetic alterations in acute myeloid leukemia. However, the prognostic significance of FLT3 mutations in acute promyelocytic leukemia [APL] is not firmly established. In this study, the chromosomal abnormalities were analyzed by bone marrow cytogenetic in 45 APL patients and FLT3 internal tandem duplications [ITD] screening by fragment length analysis and FLT3 D835 mutation by melting curve analysis were screened in 23 APL samples. Cytogenetic study showed 14.3% trisomy 8 and 17.1% chromosomal abnormalities other than t[15;17]. About 13% of the patients had FLT3 ITD, and 26% had D835 point mutation. FLT3 ITD mutation was associated with higher white blood cell count at presentation and poor prognosis. The PML-RARA translocation alone may not be sufficient to induce leukemia. Therefore, we assume that FLT3 mutations and the other genetic and chromosomal alterations may cooperate with PML-RARA in the development of APL disease

Humans , Gene Duplication , Mutation , fms-Like Tyrosine Kinase 3 , Oncogene Proteins, Fusion , Receptor Protein-Tyrosine Kinases
Middle East Journal of Digestive Diseases. 2012; 4 (3): 145-149
in English | IMEMR | ID: emr-132295


During the resent years there has been interest in using bone marrow stem cells to treat liver cirrhosis. However, there is a potential concern for malignant transformation after stem cell therapy. The aim of this study was to evaluate the development of hepatocellular carcinoma [HCC] after autologous bone marrow stem cell transplantation for liver cirrhosis. All the patients who underwent autologous stem cell transplantation for liver cirrhosis between 2005 and 2011 at our center were enrolled. Cellular infusion was made through peripheral vein, portal vein, or hepatic artery.The patients were invited to undergo screening for hepatocellular carcinoma. The screening was made with ultrasonography and alpha-feto protein [AFP] measurement. Thirty two patients [18 males] were included in the study. Mean age of patients was 45.7 years. Fifteen patients [47%] received mesenchymal stem cell [MSC], 9 [28%] received bone marrow mononuclear cells, 5 [16%] were given CD 133-positive bone marrow cells, and 3 [9%] patients received CD 34-positive bone marrow cells. Mean duration of follow up was 20.5months. Mean serum level of AFP was 2.8 ng/ml at baseline and 3.4ng/ml at the end of follow up [p= 0.3]. One patient was found to have hepatocellular carcinoma three months after infusion of bone marrow mononuclear cells. The incidence rate for HCC was 1.8 cases per 100 person-years in this study. Autologous bone marrow stem cell infusion does not appear to increase the risk of hepatocellular carcinoma. The incidence rate of HCC in this study is comparable or even less than the reported rates of HCC in cohort studies of cirrhotic patients

Hematology, Oncology and Stem Cell Therapy. 2011; 4 (2): 81-93
in English | IMEMR | ID: emr-129763


The Eastern Mediterranean Bone Marrow Transplantation [EMBMT] Group has accumulated over 25 years of data and experience in hematopoietic stem cell transplantation [HSCT], most particularly in he-moglobinopathies, severe aplastic anemia [SAA], and inherited metabolic and immune disorders, in addition to hematologic malignancies peculiar to the region and where recent updates in trends in activities are warranted. To study trends in HSCT activities in the World Health Organization-Eastern Mediterranean [EM] region surveyed by EMBMT between 2008 and 2009. STUDY DESIGN: Retrospective analysis of the survey data, mainly of the cumulative number of transplants, types of transplants [autologous vs. allogeneic], types of conditioning as myeloablative [MAC] vs. reduced intensity conditioning [RIC] and trends in leukemias, hemo-globinopathies, SAA, inherited bone marrow failure syndromes amongst others. Fourteen teams from ten Eastern Mediterranean Region Organization [EMRO] countries reported their data [100% return rate] to the EMBMT for the years 2008-2009 with a total of 2608 first HSCT [1286 in 2008; 1322 in 2009]. Allogeneic HSCT represented the majority [63%] in both years. The main indications for allogeneic HSCT were acute leukemias [732; 44%], bone marrow failure syndromes [331, 20%], hemoglobinopathies [255; 15%] and immune deficiencies [90; 5%]. There was a progressive increase in the proportions of chronic myeloid leukemia [CML] cases transplanted beyond the first chronic phase [3; 7% of all CML cases in 2008 vs 13; 29% in 2009]. The main indications for autologous transplants were plasma cell disorders [345; 36%] Hodgkin disease [256; 27%], non-Hodgkin lymphoma [207; 22%] and solid tumors [83; 9%]. RIC continued to show a progressive increase over the years [7% in 2007, 11% in 2008 and 13% in 2009], yet remained relatively low compared to contemporary practices in Europe published by EBMT. The vast majority [95%] of allo-HSCT sources were from sibling donors with a continued dominance of peripheral blood [PB] [1076; 63%], while cord blood transplant [CBT] increased to 83 [5% of allo-HSCT], matched unrelated donor [MUD] remained underutilized [1; 0%] and there were no haploidentical transplants reported. Large centers with >50 HSCT/year showed a plateau of the total number of allo-HSCT over the last 5 years that may be related to capacity issues and needs further study. There is an overall increased rate of HSCT in the EMRO region with a significant increase in utilization of CBT and allogeneic PB-HSCT as a valuable source. However, further research on outcome data and development of regional donor banks [CB and MUD] may help facilitate future planning to satisfy the regional needs and increase collaboration within the group and globally

Humans , Retrospective Studies , Health Surveys , Transplantation, Homologous , Transplantation, Autologous
Annals of Saudi Medicine. 2011; 31 (1): 45-50
in English | IMEMR | ID: emr-103650


Nucleophosmin gene mutations are frequently reported in acute myeloid leukemia [AML] patients with normal karyotype, which is also frequently associated with internal tandem duplication mutations in the FMS-like tyrosine kinase-3 gene. We sought to detect the nucleophosmin and FMS-like tyrosine kinase-3 [FLT3] internal tandem duplication [ITD] mutations among Iranian patients with AML and to assess the relationship between these mutations and the subtypes of the disease. Cross-sectional study of patients referred during 2007 through 2009. Bone marrow and peripheral blood samples of 131 AML patients were randomly collected at the time of diagnosis and prior to treatment and the DNA extracted. After amplifying the nucleophosmin and FLT3 gene regions, positive cases were screened by conformation-sensitive gel electrophoresis and agarose gel electrophoresis techniques. Of 131 patients, 23 [17.5%] [0.95% Cl=0.107-0.244] had nucleophosmin gene mutations. The highest frequency of such mutations was found among the subtypes of M4 [30.4%], M3 [21.7%] and M5 [17.4%]. There was a high frequency of these mutations in the M3 subtype as well as a high frequency of allele D in all subtypes. Also, 21 [16.0%] samples [0.95% CI=0.092-0.229] had FLT3/ITD mutation, of which 8 samples had mutant nucleophosmin [8 of 23, 35%], and another 13 samples had wild-type nucleophosmin gene [13 of 108, 12%]. There was a high degree of association between the occurrence of nucleophosmin and FLT3/ITD mutations [P=.012]. Our data showed a high frequency of NPM1 mutations in the monocytic subtypes of AML, as well as a high degree of association between the occurrence of NPM1 and FLT3/ITD mutations

Humans , Male , Female , Nuclear Proteins , fms-Like Tyrosine Kinase 3/genetics , Mutation , Cross-Sectional Studies , Electrophoresis, Agar Gel
Hematology, Oncology and Stem Cell Therapy. 2011; 4 (3): 109-115
in English | IMEMR | ID: emr-109084


Hematopoietic cell transplantation [HCT] is the only therapeutic modality capable of correcting the hematologic manifestations of Fanconi anemia [FA]. The development of well-tolerated immunosuppressive conditioning regimens for FA patients undergoing HCT has proven to be a challenging task for hematologists. Retrospective, patients referred to the hematology, oncology and stem cell transplantation research center. We analyzed the outcome of 53 FA patients who had undergone HCT between 1992 and 2010. The median age at transplantation was 9 years. Patients received transplants from an HLA-identiccal sibling [n=39] or matched relative [n=9] and one-antigen locus mismatched other relative/sibling [n=5]. All of the patients underwent transplantation with fludarabine and non-fludarabine-based conditioning regimens. No radiation therapy was given. The median follow-up period for survivors was 13.5 months [range, 3 months-13.5 years]. The 3-year overall survival [OS] was 60.6%. The 3-year OS for patients who did or did not receive fludarabine-based preparative regimens for the allograft was 36.4%, and 70%, respectively. However, there were no statistically significant differences in OS rates between these two groups [P=.112]. Graft failure occurred in 4 patients [7.5%]. All of these 4 patients had received fludarabine-based conditioning regimens. The incidence of acute GVHD after fludarabine-based regimens was 45% versus 79% in non-fludarabine-based regimens [P=.03]. Despite the high incidence of acute GVHD [78.6%] in the non-fludarabine group, which ressulted in the death of some patients, the OS rate was significantly better than in fludarabine recipients. Therefore, in spite of the fact that recent studies advocate the fludarabine-based conditioning regimens, we propose to conduct a multicenter, prospective study to evaluate the outcomes of regimens employed in FA patients

Archives of Iranian Medicine. 2011; 14 (5): 332-334
in English | IMEMR | ID: emr-122667


Acute promyelocytic leukemia is a rare indication for hematopoietic stem cell transplantation. Usually it is indicated as consolidation of salvage regimens following relpase. Here we report our experience with stem cell transplantation in acute promyelocytic leukemia patients. Between 1989 and 2011, we performed 40 hematopoietic stem cell transplantation in first complete remission or relapsed acute promyelocytic leukemia patients. Median age of patients was 23.5 years. Patients received 11 autologous and 29 allogeneic hematopoietic stem cell transplantation from their HLA fully-matched sibling donors. Different conditioning regimens were applied. A total of 24 patients received hematopoietic stem cell transplantation who were in first complete remission and the remainder with a second or more complete remission. Hematopoietic stem cell engraftment was observed in all cases. There were no deaths prior to 100 days after hematopoietic stem cell transplantation. Acute graft versus host disease was mild to moderate in the majority of patients, whereas it was grade III in 4 patients. Chronic graft versus host disease was extensive in 2 cases. With a 4-year median follow up, the relapse rate was 25%. A total of 26 patients are alive. Five year overall survival was 65.5% and 46.8% for allogeneic and autologous hematopoietic stem cell transplantation, respectively. Hematopoietic stem cell transplantation is an acceptable treatment for acute promyelocytic leukemia. Although there is a statistical difference for overall survival between allogeneic or autologous hematopoietic stem cell transplantation, the choice between autologous or allogeneic transplantation needs to have reliable methods for the detection of molecular remission before hematopoietic stem cell transplantation as well as close, reliable follow up of patients with clinical and molecular parameters

Humans , Middle Aged , Male , Female , Young Adult , Child, Preschool , Child , Adolescent , Adult , Hematopoietic Stem Cell Transplantation , Treatment Outcome , Graft vs Host Disease
Archives of Iranian Medicine. 2011; 14 (3): 167-169
in English | IMEMR | ID: emr-110311


Although standard first line treatment of acute promyelocytic leukemia is All trans retinoic acid [ATRA] and chemotherapy, some patients relapse and need a second line of treatment. Relapsed cases of promyelocytic leukemia can be salvaged with arsenic trioxide. Between May 1999 and Jan. 2010, we treated 31 relapsed cases of promyelocytic leukemia with arsenic trioxide. These cases relapsed after previous treatment with ATRA and chemotherapy. We applied arsenic trioxide as 0.15 mg/kg iv infusion until complete remission. After achieving complete remission patients received 2-4 consolidation therapy in the same schedule as remission induction. The median age of patients was 27 years. Complete remission rate was 77.4%. We observed four mortalities during remission induction. With a median follow up of 32 months, ten more relapses occurred. Two year disease-free survival and overall survival for the entire cohort was 54.6% and 81.1%, respectively. Our result is the same as other studies. Thus, we suggest that arsenic trioxide can be used as salvage therapy in patients who relapsed. Despite a good complete remission rate, the relapse rate during the first two years of treatment is high and hematopoietic stem cell transplantation should be considered after achieving complete remission

Humans , Arsenicals , Drug Therapy , Recurrence , Oxides
IJI-Iranian Journal of Immunology. 2010; 7 (1): 8-17
in English | IMEMR | ID: emr-105820


Interaction between killer cell immunoglobulin-like receptors [KIR] and human leukocyte antigen [HLA] class I molecules is important for regulation of natural killer [NK] cell function. The aim of this study was to investigate the impact of compound KIR-HLA genotype on susceptibility to acute leukemia. Cohorts of Iranian patients with acute myeloid leukemia [AML; n=40] and acute lymphoid leukemia [ALL; n=38] were genotyped for seventeen KIR genes and their three major HLA class I ligand groups [C1, C2, Bw4] by a combined polymerase chain reaction-sequence-specific primers [PCR-SSP] assay. The results were compared with those of 200 healthy control individuals. We found a significantly decreased frequency of KIR2DS3 in AML patients compared to control group [12.5% vs. 38%, odds ratio=0.23, p=0.0018]. Also, the KIR3DS1 was less common in AML group than controls [27.5% vs. 44.5%, p=0.0465, not significant after correction]. Other analyses including KIR genotypes, distribution and balance of inhibitory and activating KIR+HLA combinations, and co-inheritance of activating KIR genes with inhibitory KIR+HLA pairs were not significantly different between leukemia patients and the control group. However, in AML patients a trend toward less activating and more inhibitory KIR-HLA state was observed. Interestingly, this situation was not found in ALL patients and inhibition enhancement through increase of HLA ligands and inhibitory combinations was the main feature in this group. Our findings may suggest a mechanism for escape of leukemic cells from NK cell immunity

Humans , Male , Female , Receptors, KIR , HLA Antigens , Histocompatibility Antigens Class I , Killer Cells, Natural , Polymerase Chain Reaction , Genotype , Genetic Predisposition to Disease , Genetic Association Studies
Hematology, Oncology and Stem Cell Therapy. 2010; 3 (1): 18-23
in English | IMEMR | ID: emr-98291


Dendritic cells [DCs] play a critical role in the immune response and are a candidate for immunotherapy in cancer. Since gibbon ape leukemia virus [GALV] transduction of CD34+ cells is reasonably efficacious, we assessed the efficacy of GALV transduction of CD34+ derived DCs as a possible approach to creating genetically modified DCs for immunotherapy. Peripheral blood CD34+ cells were transduced with retroviruses obtained from the PG13/LN C8 cell line, with the neomycin gene as a marker gene. After prestimulation of hematopoietic cells for 24 hours with 10 ng/mL interleukin [IL]-3, 10 ng/mL IL-6, 100 ng/mL stem cell factor, 100 ng/mL granulocyte-macrophage colony stimulating factor and 8 micro g/mL protamine sulfate, the cells were cultured in a transforming media prior to differentiating into DCs by GM-CSF, TNF-alpha and IL-4. Immunophenotyping analyses for confirmation of the generated DCs, colony formation assay and PCR were done for the expression of neomycin gene in the transduced cells. Titration of viral vectors indicated a transduction efficiency of 1 x10[5] CFU/mL Transduction efficiency for the CD34+ cells transformed to DCs was 45% and 38% before and after DC differentiation, respectively. Additionally, a mean [SEM] of 26.9% [11.4%] and 41.4% [11.8%] of the genetically modified DCs were positive forCD86+ HLA-DRand CD1alpha+CD14, respectively. This study showed that the majority of transduced CD34+ cells were successfully differentiated into cells identical to DCs according to morphology and immunophenotyping features, which could be a potential application in immunotherapy

Humans , Antigens, CD34 , Dendritic Cells , Immunotherapy , Transduction, Genetic , Immunophenotyping
Archives of Iranian Medicine. 2008; 11 (3): 247-251
in English | IMEMR | ID: emr-143488


A specific chromosomal abnormality, the Philadelphia chromosome, is present in 90 - 95% of patients with chronic myeloid leukemia. The aberration results from a reciprocal translocation of chromosomes 9 and 22, creating a BCR-ABL fusion gene. There are two major forms of the BCR-ABL fusion gene, involving ABL exon 2, but including different exons of BCR gene. The transcript b2a2 or b3a2 codes for a p210 protein. Other fusion gene leads to the expression of an e1a2 transcript, which codes for a p190 protein. Other less common fusion genes are b3a3 or b2a3 [p203] and e19a2 [p230]. The incidence of one or other rearrangement in chronic myeloid leukemia patients varies in different reports. In general, fusion transcripts are determined individually, a process which is labor- intensive in order to detect all major fusion transcripts. The objective of this study was to set up a multiplex RT-PCR assay for detection and to determine the frequency of different fusion genes in 75 Iranian patients with chronic myeloid leukemia. Peripheral blood samples were analyzed by multiplex RT-PCR from 75 adult Iranian chronic myeloid leukemia patients to detect different types of BCR-ABL transcripts of the t[9;22]. All patients examined were positive for some type of BCR/ABL rearrangement. The majority of the patients [83%] expressed one of the p210BCR-ABL transcripts [b3a2, 62% and b2a2, 20%], while the remaining showed one of the transcripts of b3a3, b2a3, e1a2 or co-expression of b3a2 and b2a2. The rate of co-expression of the b3a2 and b2a2 was 5%. In contrast to other reports, we did not see any co-expression of p210/p190. Co-expression may be due to alternative splicing or to phenotypic variation, with clinical course different from classic chronic myeloid leukemia

Humans , Male , Female , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Fusion Proteins, bcr-abl , Reverse Transcriptase Polymerase Chain Reaction , Epidemiology , Philadelphia Chromosome
Endovascular Journal. 2008; 1 (1): 18-25
in English | IMEMR | ID: emr-86436


Stem cell transplantation after myocardial infarction has been claimed to restore cardiac function. Mesenchymal stem cells attract a lot of attention because of the feasibility of in vivo and ex vivo differentiation to cardiomyocytes and endothelial cells as well as their trophic effect on tissue repair. In this study, we investigated the efficacy of autologous bone marrow derived mesenchymal stem cells in improving heart function in patients with old myocardial infarction. Eight patients with old myocardial infarction and proper inclusion criteria were injected with mesenchymal stem cells at the time of coronary artery bypass grafting or percutaneous coronary intervention [test group] and compared with eight matched patients who received the same treatment without mesenchymal stem cell injection [control group]. Evaluation of heart function was done by echocardiography plus single-photon emission computed tomography before and six months after the procedure. Serial clinical examination was performed every month through New York Heart Association class. The mean New York Heart Association class and single-photon emission computed tomography scan results decreased significantly in the test group [P=0.000 and 0.002, respectively] and in the control group [P=0.049 and 0.007, respectively] after the procedure at six months follow-up. Left ventricular ejection fraction increased significantly in the test group [P< 0.005] but not in the control group. In comparison between the test and control groups the results of New York Heart Association class assessment and single-photon emission computed tomography demonstrated significant improvement in the test group [P=0.005 and 0.013, respectively]. There were no significant differences between the baseline variables in the two groups. In conclusion transplantation of ex vivo expanded bone marrow derived mesenchymal stem cell in patients with old myocardial infarction is a safe and feasible procedure. These cells improve the cardiac fimction without serious adverse effects

Humans , Male , Female , Myocardial Infarction/therapy , Transplantation, Autologous , In Vitro Techniques , Treatment Outcome , Heart Function Tests , Stroke Volume , Echocardiography , Tomography, Emission-Computed, Single-Photon
IJB-Iranian Journal of Biotechnology. 2007; 5 (2): 79-86
in English | IMEMR | ID: emr-112577


Experimental and clinical studies have shown that intracoronary transplantation of autologous bone marrow mesenchymal stem cells [BMSCs] has resulted in regenerated infarcted myocardium and improved left ventricular [LV] function. The aim of this pilot study was to assess the benefical effects of intracoronary transplantation of BMSC in patients with old myocardial infarction [OMI]. Autologous BMSCs were transplanted by the intracoronary method via percutaneous transluminal coronary balloon angioplasty [PTCA] in five patients with old myocardial infarction. Time from myocardial infarction [MI] to cell therapy was 5.2 +/- 3.11 months [mean +/- SD]. All patients were <70 years old [32-61 years] and had significant LV dysfunction [LV ejection fraction, mean +/- SD, 34% +/- 10.83%], and severe wall motion abnormality [akinesia and / dyskinesia] at the location of infarcted area. Follow up angiography was performed 6-9 months [mean +/- SD,7 +/- 1.4 months] after BMSC transplantation, which revealed an increased trend in the LV ejection fraction [LVEF] of patients after treatment [LVEF: Mean +/- SD from 34% +/- 10.83% to 46.25% +/- 9.46%, P= 0.051 and median from 35% to 42.5%]. Clinical follow up [for 12-18 months] also revealed appreciable improvement in their symptoms or functional class [dyspnea from New York Heart Association[NYHA]-Class Sha-IV to I-II and Chest discomfort from Canadian Cardiovascular Society [CCS] Class II-IV to I-II]. Intracoronary transplantation of autologous BMSC in patients with old myocardial infarction appears to be feasible, safe and effective .The therapeutic effect could be attributed to BMSCs ability to regenerate myocardium

Humans , Male , Female , Transplantation, Autologous , Transplantation , Bone Marrow , Bone Marrow Transplantation , Bone Marrow Cells , Mesenchymal Stem Cells , Stem Cells , Pilot Projects , Angioplasty, Balloon, Coronary