Hossein Mozdarani | Tarbiat Modares University (original) (raw)

Papers by Hossein Mozdarani

Research paper thumbnail of Expansion of Human Cord Blood Primitive Progenitors in Serum-Free Media Using Human Bone Marrow Mesenchymal Stem Cells

The Medical Journal of The Islamic Republic of Iran, Nov 15, 2004

Ex vivo expansion of human umbilical cord blood cells (HUCBC) is explored by several investigator... more Ex vivo expansion of human umbilical cord blood cells (HUCBC) is explored by several investigators to enhance the repopulating potential of HUCBC. The proliferation and expansion of human hematopoietic stem cells (HSC) in ex vivo culture was examined with the goal of generating a suitable clinical protocol for expanding HSC for patient transplantation. Using primary human mesenchymal stem cells, we established a serum-free culture system to expand human primitive progenitors and transplantable stem cells. Non-enriched cord blood CD34+ cells were cultured on a monolayer of human mesenchymal stem cells in the presence of tlu-ombopoietin (TPO), flt31flk2 ligand (FL), and/or stem cell factor (SCF), interleukin 6 (IL-6), interleukin 3 (IL-3) under serum-free conditions. After I or 2 weeks of culture, cells were examined for clonogenic progenitors and percentage of CD34+ CD38-cells. In the presence of TPO, FL, and SCF, fetal MSC cells supported more than a 35-and 20-fold expansion of CD34+ cells and colony-fOlming units in culture after 1 and 2 weeks of incubation, respectively. In addition, LTC-IC assay were expanded more than 7-and 16-fold after 1 and 2 weeks of culture, respectively. UCB-HSC can be expanded in culture to numbers theoretically adequate for safe, rapid engrafiment of adult patients. Additional studies are needed

Research paper thumbnail of The Interaction of Radiation and Intercalating Agents in Normal Bone Marrow Cells as Evaluated by Spleen Colony Assay Technique: The Effects of Bleomycin Sulfate and Act Inomycind

The Medical Journal of The Islamic Republic of Iran, Aug 15, 1995

The relationship between the way in which normal hemopoietic stem cells respond to irradiation al... more The relationship between the way in which normal hemopoietic stem cells respond to irradiation alone or in the presence of bleomycin sulfate (BLM-S) and actinomycin 0 (ACT-D) was investigated. Single doses of BLM-S at 0.3 mg/kg and ACT-O at 0.10 mg/kg body weight were injected intravenously 1-6 hours prior to whole body irradiation and treatment was repeated twice more with time intervals. When assessed by survival of spleen colony forming units (CFU-S) of bone marrow cells (BMC), BLM-S alone caused only 10% reduction in survival compared to controls. There was not a significant difference in survival fraction (SF) when treatment with BLM-S was repeated twice more. On the other hand, ACT-O alone caused a 45% reduction in SF after the first injection and only a 10% reduction after the third injection. Increase in survival might be due to resistance induced in BMC after treatments with the drugs. The difference between the 'SF of BMC of mice exposed to doses of 1-3 Gy whole body irradiation was statis tically significant with a p-value <0.05. When used in combination with radiation, neither BLM-S nor ACT-O caused a synergistic or additive effect. Although survival was seen to be lower for ACT-O treated animals, the effect was not as pronounced as expected. A significant change in the results was also not observed for fractionated doses of gamma rays in the presence of BLM-S and ACT-O injected at various time intervals. Results obtained from the administration of drugs at various time intervals before irradiation does not suggest a specific time for drug treatment prior to irradiation. These results also suggest that no potentiating effect is likely to be produced by a combination of BLM-S or ACT-O and radiation therapy in bone marrow cells. We therefore believe that these drugs induce a modest resistive re sponse to the effects of radiation on bone marrow cells by a mechanism which is not yet understood. Therefore, using this agent repeatedly for can cer treatment might not cause severe adverse biological effects in bone mar row stem cells.

Research paper thumbnail of Radio-adaptive response of peripheral blood lymphocytes following bystander effects induced by preirradiated CHO-K1 cells using the micronucleus assay

Iranian Journal of Radiation Research, Apr 10, 2015

Background: Radio-adap ve response and bystander effects are known phenomena occurring in cells f... more Background: Radio-adap ve response and bystander effects are known phenomena occurring in cells following exposure to ionizing radia on (IR). In this study we examined possible radio-adapta on of lymphocytes following bystander effects induced by CHO-K1 cells. Materials and Methods: Whole blood and CHO-K1 cells were cultured in RPMI-1640 complete medium. Cells were separately irradiated with various doses of gamma rays. A co-culture was set to examine the bystander effects induced by CHO-K1 cells on lymphocytes exposed later to a challenge dose of 4 Gy. Treated cells were exposed to cytochalasin-B to arrest cells in cytokinesis stage. Micronucleus (MN) as end point was scored in binucleate cells a2er staining in Giemsa. The frequency of MN increased significantly with increasing dose of radia on both in lymphocytes and CHO-K1 cells (p<0.001). Although, no significant difference was observed between control non-irradiated cells and those exposed to 0.2 Gy (p>0.05). Co-culture of the non-irradiated lymphocytes with pre-irradiated CHO-K1 cells significantly reduced the mean frequency of MN in lymphocytes irradiated with a dose of 4Gy (p<0.001). Results showed that bystander effects induced by gammairradiated CHO-K1 cells led to induc on of radio-adap ve response in lymphocytes. The mechanism by which radio-adap ve response is induced following bystander effect is not clearly known, however cellular signaling and genome instability induced in cells indirectly might be considered as possible triggering events for radio-adap ve response.

Research paper thumbnail of Uncertainties in radiation sciences: The need for more researches and publications. Experience of 10 years publications in this field and our new plans

Iranian Journal of Radiation Research, Jan 10, 2013

Research paper thumbnail of Can previous thyroid scan induce cytogenetic radioadaptive response in patients treated by radioiodine for hyperthyroidism

Iranian Journal of Radiation Research, Sep 10, 2004

T here is no doubt that low doses of ionizing radiation (conditioning dose) can induce resistance... more T here is no doubt that low doses of ionizing radiation (conditioning dose) can induce resistance to subsequent higher (challenge) exposures. This phenomenon is termed radio-

Research paper thumbnail of Determination of dose-response relationship in cultured human lymphocytes for biological dosimetry

Iranian Journal of Radiation Research, Sep 10, 2004

Background: Lymphocyte-dicentric assay is the most generally accepted method for biological dosim... more Background: Lymphocyte-dicentric assay is the most generally accepted method for biological dosimetry of overexposed individuals. In this study, the frequency of unstable chromosome aberration in blood lymphocytes was used to estimate radiation dose received by individuals. Evaluation of dose using a calibration curve produced elsewhere may have a significant uncertainty; therefore, experiments were performed to produce a dose-response curve using an established protocol of international atomic energy agency. Materials and Methods: Lymphocytes in whole peripheral blood obtained from healthy individuals, were exposed to various doses of gamma radiation (0.25 -4 Gy). Then after 1 hour of incubation in 37 o C, were cultured in complete RPMI-1640 medium. 500 mitoses were analysed for the presence or absence of unstable chromosomal aberrations for each radiation dose after the standard metaphase preparation and staining slides. Results and Conclusion: Intercellular distribution of dicentric chromosomes at each radiation dose has been used to contrast a dose-response curve. It seems that dose-effect relationship follows with the linear-quadratic model. There is a good agreement between our dose-response curves with similar published studies by other laboratories.

Research paper thumbnail of Cytogenetic Bionionitoring of 65 Radiology Technologiests Occupationally Exposed to Chronic Doses of X-Irradiation in Iran

The Medical Journal of The Islamic Republic of Iran, May 15, 1996

The frequency of chromosomal aberrations was studied in the peripheral blood lymphocytes of 65 ra... more The frequency of chromosomal aberrations was studied in the peripheral blood lymphocytes of 65 radiology technologists CRT) working at hospitals chronically exposed to x-rays. Although film dosimetry did not show the maximal annual permitted dose in any of the examined subjects, cytogenetic analysis detected fairly high levels of chromosomal aberrations in R T compared to unexposed controls. The mean frequencies of structural chromosome aberration per 100 lymphocyte metaphases of workers and the controls were 2.93 and 0.54; respectively, excluding the high level of achromatic lesions registered. The difference between them was statistically significant with a P-value of <0.05.

Research paper thumbnail of The Potent Regulatory Role of Circular RNAs in Breast Cancer Development, Diagnosis and Treatment: An Update

Journal of Cancer Research Updates, Oct 7, 2022

Breast cancer (BC) is one of the most frequent malignant diseases among women worldwide. Circular... more Breast cancer (BC) is one of the most frequent malignant diseases among women worldwide. Circular RNAs (circRNAs) as a novel class of noncoding RNA (ncRNA), display unique features due to their specific circular configuration. One of the important roles of CircRNAs is the regulation of gene expression via different mechanisms, including sponging microRNAs and proteins. Moreover, evidence indicates that circRNAs act as key regulators in the initiation and progression of BC. Currently, many circRNAs have been reported to be associated with different biological processes of BC, such as cell division, migration, invasion, and programmed cell death. The aim of this review was to provide a concise overview of the biogenesis and roles of circRNAs and track the related knowledge in BC development, diagnoses and treatment.

Research paper thumbnail of Effect of Class Switch Recombination Defect on the Phenotype of Ataxia-Telangiectasia Patients

Immunological Investigations, Mar 2, 2020

Research paper thumbnail of Biological Complexities in Radiation Carcinogenesis and Cancer Radiotherapy: Impact of New Biological Paradigms

Genes, Jan 20, 2012

Although radiation carcinogenesis has been shown both experimentally and epidemiologically, the u... more Although radiation carcinogenesis has been shown both experimentally and epidemiologically, the use of ionizing radiation is also one of the major modalities in cancer treatment. Various known cellular and molecular events are involved in carcinogenesis. Apart from the known phenomena, there could be implications for carcinogenesis and cancer prevention due to other biological processes such as the bystander effect, the abscopal effect, intrinsic radiosensitivity and radioadaptation. Bystander effects have consequences for mutation initiated cancer paradigms of radiation carcinogenesis, which provide the mechanistic justification for low-dose risk estimates. The abscopal effect is potentially important for tumor control and is mediated through cytokines and/or the immune system (mainly cell-mediated immunity). It results from loss of growth and stimulatory and/or immunosuppressive factors from the tumor. Intrinsic radiosensitivity is a feature of some cancer prone chromosomal breakage syndromes such as ataxia telangectiasia. Radiosensitivity is manifested as higher chromosomal aberrations and DNA repair impairment is now known as a good biomarker for breast cancer screening and prediction of prognosis. However, it is not yet known whether this effect is good or bad for those receiving radiation or radiomimetic agents for treatment. Radiation hormesis is another major concern for carcinogenesis. This process which protects cells from higher doses of radiation or radio mimic chemicals, may lead to the escape of cells from mitotic death or apoptosis and put cells with a lower amount of damage into the process of cancer induction. Therefore, any of these biological phenomena could have impact on another process giving rise to genome instability of cells which are not in the field of radiation but still receiving a lower amount of radiation. For prevention of radiation induced carcinogenesis or risk assessment as well as for successful radiation therapy, all these phenomena should be taken into account.

Research paper thumbnail of On the effects of ara-A and ara-C on X-ray-induced DNA lesions in normal human and A-T cells: similarities and differences

Mutation research, 1992

A better understanding of the mechanism of chromosomal aberration formation could be obtained by ... more A better understanding of the mechanism of chromosomal aberration formation could be obtained by using DNA repair inhibitors. Immortalized normal human (MRC 5 SVI) and ataxia telangiectasia ( AT 5 BIV A ) fibroblastic cell lines were treated with adenosine arabinoside (ara-A) and cytosine arabinoside (ara-C), both potent inhibitors of DNA dsb repair, alone or in combination with x-rays at G2 or S-phase of the cell cycle. The length of G2-phase for both cell lines was determined by autoradiographic labeling to be about 4.5-5 h. A similar result was obtained by scoring of chromosomally damaged cells following treatment with ara-A or ara-C for various time intervals before fixation. The results obtained in this study show that in spite of many similarities between the action of ara-A and ara-C, e.g., inhibition of DNA synthesis cIastogenic effects at G2 and S-phase and also lack of synergism as a possible consequence of these similarities, ara-A was found to have a different effect on rejoining of x-ray induced DNA lesions than that of ara-C. Ara-A caused inhibition of chromatid deletion rejoining, interpreted as inhibition of rejoining of DNA dsb at all sampling times before fixation, whereas ara-C showed a synergistic effect on radiation-induced DNA lesions, resulting in an increased frequency of chromatid deletions. Thus there appears that these inhibitors have different modes of action on x-ray induced DNA lesions, which may suggest a peculiar and important difference in the nature of these two nucIeosides.

Research paper thumbnail of The role and mechanisms of zinc oxide nanoparticles in the improvement of the radiosensitivity of lung cancer cells in clinically relevant megavoltage radiation energies in-vitro

Nanomedicine Journal, Oct 1, 2019

Semiconductor zinc oxide nanoparticles (ZnO NPs) have unique properties, such as inherent selecti... more Semiconductor zinc oxide nanoparticles (ZnO NPs) have unique properties, such as inherent selectivity and photosensitization effects under ultraviolet (UV) radiation. ZnO NPs serve as promising anticancer agents. However, UV radiation limits their penetration into the body. In most clinical settings, it is essential to use high-energy photons in the treatment of deep-seated tumors. The present study aimed to evaluate the radiosensitization effects of ZnO NPs on human lung cancer cells under megavoltage (MV) X-ray irradiation. Materials and Methods: ZnO NPs with the mean diameter of seven nanometers were synthesized and characterized. The cytotoxicity and cellular uptake of ZnO NPs were evaluated in SKLC-6 lung cancer and MRC-5 normal lung cells using the 3-(4,5-dimethylthiazol-yl)-5(3-carboxymethoxyphenyl)-2Htetrazolium (MTT) and inductively coupled plasma-mass spectrometry assays, respectively. In addition, the radiosensitization effects of ZnO NPs were investigated under MV irradiation using a clonogenic survival assay. Apoptosis induction and DNA damage were also evaluated using flow cytometry and cytokinesisblock micronucleus assay, respectively. Results: ZnO NPs were taken up and reduced the viability of the cancer cells at a higher rate compared to the normal cells. Moreover, ZnO NPs significantly enhanced the radiosensitivity of the cancer cells with the sensitizer enhancement ratios of 1.23 and 1.31 at the concentrations of 10 and 20 μg/ml, respectively. However, they had no significant effect on the radiosensitivity of the normal cells. Apoptosis induction and DNA damage also improved at a higher rate in the cancer cells compared to the normal cells with the combination of ZnO NPs with MV radiation. Conclusion: According to the results, ZnO NPs had the potential to be a selective radiosensitizer for lung cancer radiotherapy under MV X-ray irradiation. Some of the cytotoxic and genotoxic mechanisms in radiosensitization by ZnO NPs were elevated apoptosis induction and DNA damage levels.

Research paper thumbnail of Being on the right path

Iranian Journal of Radiation Research, Jun 15, 2005

The 1 st issue of the Iranian Journal of Radiation Research (IJRR) was published two years ago (J... more The 1 st issue of the Iranian Journal of Radiation Research (IJRR) was published two years ago (June 2003). This journal was initiated to bring together the various disciplines of radiation oncology, radiation biology, medical physics, nuclear medicine and other related subjects to intensify the dialogue between basic and clinical researchers especially those working in Iran. Within the last two years, this journal has tried to offer an ideal platform for the exchange of detailed scientific information concerning the latest developments in the field of radiation research, from various institutes, hospitals or even individuals. IJRR has been one of the specialized journals when published 2 years ago. The executive committee of the journal has been anxious about the quality and quantity of papers received by the IJRR office. The reason is that, the research activities in these fields are unexplored. Then, we believed that there might not be sufficient numbers of articles to be published in a specialized magazine as IJRR. Now, only a little over 2 years we have realized potential peoples and centers working in this area, not only in Iran but in other countries who contributed sincerely to the journal so that we are not worried about the materials to be published. We have realized that the existence of such a unique journal is a must both for Iran and the researchers in the region. Shortly after publishing the 1 st issue, we tried to computerize all activities in the editorial office, including online review by our reviewers. The journal's website is one of the most complete websites among Iranian journals with search capabilities and free access to abstracts and full PDF texts by readers and our visitors. The scientific quality of the journal specifically depends on the quality of papers submitted and the keen attention of the journal's reviewers. These efforts were led to recognition of the journal as a scientific and academic research source by the ministry of Health and Medical Education. It has also been indexed by Index Medicus for Eastern Mediterranean Region (IMEMR). And now, in an annual qualification of scientific medical journals, IJRR is ranked among the highest scored journals. We are proud to publish the 3 rd volume of the journal with a short delay. To fulfill the interest of our readers and taking another step toward being internationally published in the field of radiation research, we have made some changes in the structural appearance and reference citation according to Vancouver's format. We would like to express our special thanks to our editorial board for their help and suggestions, all reviewers for their sincere help and careful review of the articles and my colleagues at the editorial and publishing office. I doubt we could publish this journal without their interest and efforts. IJRR is looking forward to receiving the invaluable papers from Iranian and foreigner scientists to be published in the forthcoming issues.

Research paper thumbnail of The Primed In Situ (PRINS) technique: an alternative approach for preimplantation chromosomal diagnosis

Iranian Journal of Biotechnology, Jul 1, 2004

Preimplantation genetic diagnosis (PGD) is a novel approach for the prevention of genetic disorde... more Preimplantation genetic diagnosis (PGD) is a novel approach for the prevention of genetic disorders in couples at risk of having offspring with genetic disease. Although the original idea dates back to early 1960s when sexing of rabbit blastocysts was attempted, the first clinical application of PGD was reported about three decades later, describing the use of PCR for sexing embryos from couples at risk of X-linked disease. The development of PCR-based tests led to PGD for screening well known monogenic diseases such as thalassaemia and cystic fibrosis. The introduction of fluorescence in situ hybridization (FISH) quickly replaced PCR-based methods which had led to misdiagnoses for sexing embryos. FISH can be used for aneuploidy screening of up to seven clinically significant chromosomes and translocation detection. The advent of molecular genetic techniques has brought forth new procedures for in situ chromosomal analysis. One of these techniques is the primed in situ labeling (PRINS) procedure which constitutes a fast and efficient alternative to conventional fluorescence in situ hybridization for nucleic acid detection. This technique has the potential to become a powerful tool for cytogenetic investigations. The recent achievements reported show that PRINS can constitute an efficient complement to PCR and FISH. Adaptation of this technique to preimplantation embryo screening both at chromosomal level and gene localization opens a promising perspective for being used in the field of PGD.

Research paper thumbnail of Induction of DNA damage, apoptosis and micronuclei in peripheral blood lymphocytes following injection of contrast media in patients with abdominal CT scan

International journal of radiation research, Apr 1, 2017

Background: Medical diagnos c procedures such as X-ray and computed Tomography (CT) scan account ... more Background: Medical diagnos c procedures such as X-ray and computed Tomography (CT) scan account for considerable percent of pa ent's exposure to ionizing radia on. The exposure of cells to Ioniza on radia on results in induc on of DNA damage and chromosomal aberra ons. Contrast media (CM) are widely used in diagnos c radiology and CT scan. The aim of this study was to study adverse gene c effects of combined administra on of non ionic contrast media and low dose X-rays in peripheral blood Lymphocytes of pa ents following abdominal CT scan. Materials and Methods: A total of 55 pa ents underwent abdominal CT scan with injec on of non ionic contrast media (30 pa ents with omnipaque 300 mg/ml and 25 pa ents with visipaque 270 mg/ml) as well as 13 pa ents undergoing abdominal CT scan (without contrast), selected as control group, were enrolled in this study. Peripheral blood leukocytes were obtained in heparin containing tubes and cultured for the micronucleus test, or were directly used for apoptosis and DNA damage with the neutral comet assay. Results: The frequency of micronuclei, apoptosis and percentage of DNA damage was increased in most pa ents a5er the injec on of contrast media, significantly different from the control group as compared with the samples obtained before and a5er injec on of contrast media (P<0.05). Conclusion: The present study suggest that non ionic contrast media (omnipaque 300 mg/ml and visipaque 270 mg/ ml) may cause a significant increase of cytogene c damage in peripheral blood lymphocytes. This effect might be caused by the enhancement of radia on dose by CM that eventually may lead to the manifesta on of ill health such as cancer.

Research paper thumbnail of Cellular S-value of beta emitter radionuclide’s determined using Geant4 Monte Carlo toolbox, comparison to MIRD S-values

iranian journal of nuclear medicine, 2016

Introduction: Spatial dose distribution around the radionuclides sources is required for optimize... more Introduction: Spatial dose distribution around the radionuclides sources is required for optimized treatment planning in radioimmunotherapy. At present, the main source of data for cellular dosimetry is the s-values provided by MIRD. However, the MIRD s-values have been calculated based on analytical formula in which no electrons straggling is taken to account. In this study, we used Geant4-DNA Monte Carlo toolbox to calculate s-values and the results were compared to the corresponding MIRD data. Methods: Similar to MIRD cell model, two concentric spheres representing the cell and its nucleus were used as the geometry of simulation. The cells were assumed to be made of water. Cellular s-values were calculated for three beta emitter radionuclides 131 I, 90 Y and 177 Lu that are widely used in radioimmunotherapy. Few lines of code in C++ were added into Geant4-DNA codes to automatically calculate the s-values and transfer data into excel files. The differences between two series of data were analyzed using Pearson's correlation and Bland-Altman curves. We observed high correlation (R 2 >0.99) between two series of data for self-absorption; however, the agreement was very weak and Wilcoxon signed rank test showed significant difference (p-value<0.001). In cross-absorption, Bland-Altman analysis showed a considerable bias between MIRD s-values and corresponding Geant4-DNA data. The percent differences between the data were -79% to +67%. Results of the comparison show a reflection of systematic error rather than statistical fluctuation. The inconsistency is most probably associated with the neglecting of straggling and δ-ray transport in MIRD analytical method.

Research paper thumbnail of A biallelic loss-of-function variant in TMEM147 causes profound intellectual disability and spasticity

Research paper thumbnail of Evaluation of the potential diagnostic role of the Lnc-MIAT, miR-29a-3p, and FOXO3a ceRNA networks as non-invasive circulatory biomarkers in ductal carcinoma breast cancer

Over the last few decades, tremendous progress has been achieved in the early detection and treat... more Over the last few decades, tremendous progress has been achieved in the early detection and treatment of breast cancer. However, the prognosis remains unsatisfactory, and the underlying processes of carcinogenesis are still unclear. The purpose of this research was to find out the relationship between MIAT, FOXO3a, and miRNA29a-3p and evaluated the expression levels of them in breast cancer tissue compared to whole blood and their potential as a noninvasive biomarker in whole blood in breast cancer. Whole blood and breast cancer tissue are taken from patients before radiotherapy and chemotherapy. Total RNA was extracted from breast cancer tissue and whole blood to synthesize complementary DNA (cDNA). The expression of MIAT, FOXO3a and miRNA29a-3p was analyzed by the RT-qPCR method and the sensitivity and specificity of them were determined by the receiver operating characteristic (ROC) curve. Bioinformatics analysis was used to understand the connections between MIAT, FOXO3a, and mi...

Research paper thumbnail of • Editor's Commentary Seven years publication of "Iranian Journal of Radiation Research" with confident but cautious steps

The Iranian Journal of Radiation Research (IJRR) is now in the eighth year of publication. This j... more The Iranian Journal of Radiation Research (IJRR) is now in the eighth year of publication. This journal is the mouth piece of shared idea of Dr Shahram Akhlaghpoor and me, which was established way back in 2002. At that time the main emphasis of the founder members was to make the subject of radiation research attractive and interesting especially for combating cancer and risk assessment. The dream for creating the Journal has come true by the help of Dr Seyed Mahmood Aghamiri who obtained the necessary permission for its publication and the Novin Medical Radiation Institute for financial and logistic supports.

Research paper thumbnail of Investigation of Expression and Methylation Status of ELF5 Gene Promoter in Patients with Breast Cancer

scientific journal of ilam university of medical sciences, 2020

Research paper thumbnail of Expansion of Human Cord Blood Primitive Progenitors in Serum-Free Media Using Human Bone Marrow Mesenchymal Stem Cells

The Medical Journal of The Islamic Republic of Iran, Nov 15, 2004

Ex vivo expansion of human umbilical cord blood cells (HUCBC) is explored by several investigator... more Ex vivo expansion of human umbilical cord blood cells (HUCBC) is explored by several investigators to enhance the repopulating potential of HUCBC. The proliferation and expansion of human hematopoietic stem cells (HSC) in ex vivo culture was examined with the goal of generating a suitable clinical protocol for expanding HSC for patient transplantation. Using primary human mesenchymal stem cells, we established a serum-free culture system to expand human primitive progenitors and transplantable stem cells. Non-enriched cord blood CD34+ cells were cultured on a monolayer of human mesenchymal stem cells in the presence of tlu-ombopoietin (TPO), flt31flk2 ligand (FL), and/or stem cell factor (SCF), interleukin 6 (IL-6), interleukin 3 (IL-3) under serum-free conditions. After I or 2 weeks of culture, cells were examined for clonogenic progenitors and percentage of CD34+ CD38-cells. In the presence of TPO, FL, and SCF, fetal MSC cells supported more than a 35-and 20-fold expansion of CD34+ cells and colony-fOlming units in culture after 1 and 2 weeks of incubation, respectively. In addition, LTC-IC assay were expanded more than 7-and 16-fold after 1 and 2 weeks of culture, respectively. UCB-HSC can be expanded in culture to numbers theoretically adequate for safe, rapid engrafiment of adult patients. Additional studies are needed

Research paper thumbnail of The Interaction of Radiation and Intercalating Agents in Normal Bone Marrow Cells as Evaluated by Spleen Colony Assay Technique: The Effects of Bleomycin Sulfate and Act Inomycind

The Medical Journal of The Islamic Republic of Iran, Aug 15, 1995

The relationship between the way in which normal hemopoietic stem cells respond to irradiation al... more The relationship between the way in which normal hemopoietic stem cells respond to irradiation alone or in the presence of bleomycin sulfate (BLM-S) and actinomycin 0 (ACT-D) was investigated. Single doses of BLM-S at 0.3 mg/kg and ACT-O at 0.10 mg/kg body weight were injected intravenously 1-6 hours prior to whole body irradiation and treatment was repeated twice more with time intervals. When assessed by survival of spleen colony forming units (CFU-S) of bone marrow cells (BMC), BLM-S alone caused only 10% reduction in survival compared to controls. There was not a significant difference in survival fraction (SF) when treatment with BLM-S was repeated twice more. On the other hand, ACT-O alone caused a 45% reduction in SF after the first injection and only a 10% reduction after the third injection. Increase in survival might be due to resistance induced in BMC after treatments with the drugs. The difference between the 'SF of BMC of mice exposed to doses of 1-3 Gy whole body irradiation was statis tically significant with a p-value <0.05. When used in combination with radiation, neither BLM-S nor ACT-O caused a synergistic or additive effect. Although survival was seen to be lower for ACT-O treated animals, the effect was not as pronounced as expected. A significant change in the results was also not observed for fractionated doses of gamma rays in the presence of BLM-S and ACT-O injected at various time intervals. Results obtained from the administration of drugs at various time intervals before irradiation does not suggest a specific time for drug treatment prior to irradiation. These results also suggest that no potentiating effect is likely to be produced by a combination of BLM-S or ACT-O and radiation therapy in bone marrow cells. We therefore believe that these drugs induce a modest resistive re sponse to the effects of radiation on bone marrow cells by a mechanism which is not yet understood. Therefore, using this agent repeatedly for can cer treatment might not cause severe adverse biological effects in bone mar row stem cells.

Research paper thumbnail of Radio-adaptive response of peripheral blood lymphocytes following bystander effects induced by preirradiated CHO-K1 cells using the micronucleus assay

Iranian Journal of Radiation Research, Apr 10, 2015

Background: Radio-adap ve response and bystander effects are known phenomena occurring in cells f... more Background: Radio-adap ve response and bystander effects are known phenomena occurring in cells following exposure to ionizing radia on (IR). In this study we examined possible radio-adapta on of lymphocytes following bystander effects induced by CHO-K1 cells. Materials and Methods: Whole blood and CHO-K1 cells were cultured in RPMI-1640 complete medium. Cells were separately irradiated with various doses of gamma rays. A co-culture was set to examine the bystander effects induced by CHO-K1 cells on lymphocytes exposed later to a challenge dose of 4 Gy. Treated cells were exposed to cytochalasin-B to arrest cells in cytokinesis stage. Micronucleus (MN) as end point was scored in binucleate cells a2er staining in Giemsa. The frequency of MN increased significantly with increasing dose of radia on both in lymphocytes and CHO-K1 cells (p<0.001). Although, no significant difference was observed between control non-irradiated cells and those exposed to 0.2 Gy (p>0.05). Co-culture of the non-irradiated lymphocytes with pre-irradiated CHO-K1 cells significantly reduced the mean frequency of MN in lymphocytes irradiated with a dose of 4Gy (p<0.001). Results showed that bystander effects induced by gammairradiated CHO-K1 cells led to induc on of radio-adap ve response in lymphocytes. The mechanism by which radio-adap ve response is induced following bystander effect is not clearly known, however cellular signaling and genome instability induced in cells indirectly might be considered as possible triggering events for radio-adap ve response.

Research paper thumbnail of Uncertainties in radiation sciences: The need for more researches and publications. Experience of 10 years publications in this field and our new plans

Iranian Journal of Radiation Research, Jan 10, 2013

Research paper thumbnail of Can previous thyroid scan induce cytogenetic radioadaptive response in patients treated by radioiodine for hyperthyroidism

Iranian Journal of Radiation Research, Sep 10, 2004

T here is no doubt that low doses of ionizing radiation (conditioning dose) can induce resistance... more T here is no doubt that low doses of ionizing radiation (conditioning dose) can induce resistance to subsequent higher (challenge) exposures. This phenomenon is termed radio-

Research paper thumbnail of Determination of dose-response relationship in cultured human lymphocytes for biological dosimetry

Iranian Journal of Radiation Research, Sep 10, 2004

Background: Lymphocyte-dicentric assay is the most generally accepted method for biological dosim... more Background: Lymphocyte-dicentric assay is the most generally accepted method for biological dosimetry of overexposed individuals. In this study, the frequency of unstable chromosome aberration in blood lymphocytes was used to estimate radiation dose received by individuals. Evaluation of dose using a calibration curve produced elsewhere may have a significant uncertainty; therefore, experiments were performed to produce a dose-response curve using an established protocol of international atomic energy agency. Materials and Methods: Lymphocytes in whole peripheral blood obtained from healthy individuals, were exposed to various doses of gamma radiation (0.25 -4 Gy). Then after 1 hour of incubation in 37 o C, were cultured in complete RPMI-1640 medium. 500 mitoses were analysed for the presence or absence of unstable chromosomal aberrations for each radiation dose after the standard metaphase preparation and staining slides. Results and Conclusion: Intercellular distribution of dicentric chromosomes at each radiation dose has been used to contrast a dose-response curve. It seems that dose-effect relationship follows with the linear-quadratic model. There is a good agreement between our dose-response curves with similar published studies by other laboratories.

Research paper thumbnail of Cytogenetic Bionionitoring of 65 Radiology Technologiests Occupationally Exposed to Chronic Doses of X-Irradiation in Iran

The Medical Journal of The Islamic Republic of Iran, May 15, 1996

The frequency of chromosomal aberrations was studied in the peripheral blood lymphocytes of 65 ra... more The frequency of chromosomal aberrations was studied in the peripheral blood lymphocytes of 65 radiology technologists CRT) working at hospitals chronically exposed to x-rays. Although film dosimetry did not show the maximal annual permitted dose in any of the examined subjects, cytogenetic analysis detected fairly high levels of chromosomal aberrations in R T compared to unexposed controls. The mean frequencies of structural chromosome aberration per 100 lymphocyte metaphases of workers and the controls were 2.93 and 0.54; respectively, excluding the high level of achromatic lesions registered. The difference between them was statistically significant with a P-value of <0.05.

Research paper thumbnail of The Potent Regulatory Role of Circular RNAs in Breast Cancer Development, Diagnosis and Treatment: An Update

Journal of Cancer Research Updates, Oct 7, 2022

Breast cancer (BC) is one of the most frequent malignant diseases among women worldwide. Circular... more Breast cancer (BC) is one of the most frequent malignant diseases among women worldwide. Circular RNAs (circRNAs) as a novel class of noncoding RNA (ncRNA), display unique features due to their specific circular configuration. One of the important roles of CircRNAs is the regulation of gene expression via different mechanisms, including sponging microRNAs and proteins. Moreover, evidence indicates that circRNAs act as key regulators in the initiation and progression of BC. Currently, many circRNAs have been reported to be associated with different biological processes of BC, such as cell division, migration, invasion, and programmed cell death. The aim of this review was to provide a concise overview of the biogenesis and roles of circRNAs and track the related knowledge in BC development, diagnoses and treatment.

Research paper thumbnail of Effect of Class Switch Recombination Defect on the Phenotype of Ataxia-Telangiectasia Patients

Immunological Investigations, Mar 2, 2020

Research paper thumbnail of Biological Complexities in Radiation Carcinogenesis and Cancer Radiotherapy: Impact of New Biological Paradigms

Genes, Jan 20, 2012

Although radiation carcinogenesis has been shown both experimentally and epidemiologically, the u... more Although radiation carcinogenesis has been shown both experimentally and epidemiologically, the use of ionizing radiation is also one of the major modalities in cancer treatment. Various known cellular and molecular events are involved in carcinogenesis. Apart from the known phenomena, there could be implications for carcinogenesis and cancer prevention due to other biological processes such as the bystander effect, the abscopal effect, intrinsic radiosensitivity and radioadaptation. Bystander effects have consequences for mutation initiated cancer paradigms of radiation carcinogenesis, which provide the mechanistic justification for low-dose risk estimates. The abscopal effect is potentially important for tumor control and is mediated through cytokines and/or the immune system (mainly cell-mediated immunity). It results from loss of growth and stimulatory and/or immunosuppressive factors from the tumor. Intrinsic radiosensitivity is a feature of some cancer prone chromosomal breakage syndromes such as ataxia telangectiasia. Radiosensitivity is manifested as higher chromosomal aberrations and DNA repair impairment is now known as a good biomarker for breast cancer screening and prediction of prognosis. However, it is not yet known whether this effect is good or bad for those receiving radiation or radiomimetic agents for treatment. Radiation hormesis is another major concern for carcinogenesis. This process which protects cells from higher doses of radiation or radio mimic chemicals, may lead to the escape of cells from mitotic death or apoptosis and put cells with a lower amount of damage into the process of cancer induction. Therefore, any of these biological phenomena could have impact on another process giving rise to genome instability of cells which are not in the field of radiation but still receiving a lower amount of radiation. For prevention of radiation induced carcinogenesis or risk assessment as well as for successful radiation therapy, all these phenomena should be taken into account.

Research paper thumbnail of On the effects of ara-A and ara-C on X-ray-induced DNA lesions in normal human and A-T cells: similarities and differences

Mutation research, 1992

A better understanding of the mechanism of chromosomal aberration formation could be obtained by ... more A better understanding of the mechanism of chromosomal aberration formation could be obtained by using DNA repair inhibitors. Immortalized normal human (MRC 5 SVI) and ataxia telangiectasia ( AT 5 BIV A ) fibroblastic cell lines were treated with adenosine arabinoside (ara-A) and cytosine arabinoside (ara-C), both potent inhibitors of DNA dsb repair, alone or in combination with x-rays at G2 or S-phase of the cell cycle. The length of G2-phase for both cell lines was determined by autoradiographic labeling to be about 4.5-5 h. A similar result was obtained by scoring of chromosomally damaged cells following treatment with ara-A or ara-C for various time intervals before fixation. The results obtained in this study show that in spite of many similarities between the action of ara-A and ara-C, e.g., inhibition of DNA synthesis cIastogenic effects at G2 and S-phase and also lack of synergism as a possible consequence of these similarities, ara-A was found to have a different effect on rejoining of x-ray induced DNA lesions than that of ara-C. Ara-A caused inhibition of chromatid deletion rejoining, interpreted as inhibition of rejoining of DNA dsb at all sampling times before fixation, whereas ara-C showed a synergistic effect on radiation-induced DNA lesions, resulting in an increased frequency of chromatid deletions. Thus there appears that these inhibitors have different modes of action on x-ray induced DNA lesions, which may suggest a peculiar and important difference in the nature of these two nucIeosides.

Research paper thumbnail of The role and mechanisms of zinc oxide nanoparticles in the improvement of the radiosensitivity of lung cancer cells in clinically relevant megavoltage radiation energies in-vitro

Nanomedicine Journal, Oct 1, 2019

Semiconductor zinc oxide nanoparticles (ZnO NPs) have unique properties, such as inherent selecti... more Semiconductor zinc oxide nanoparticles (ZnO NPs) have unique properties, such as inherent selectivity and photosensitization effects under ultraviolet (UV) radiation. ZnO NPs serve as promising anticancer agents. However, UV radiation limits their penetration into the body. In most clinical settings, it is essential to use high-energy photons in the treatment of deep-seated tumors. The present study aimed to evaluate the radiosensitization effects of ZnO NPs on human lung cancer cells under megavoltage (MV) X-ray irradiation. Materials and Methods: ZnO NPs with the mean diameter of seven nanometers were synthesized and characterized. The cytotoxicity and cellular uptake of ZnO NPs were evaluated in SKLC-6 lung cancer and MRC-5 normal lung cells using the 3-(4,5-dimethylthiazol-yl)-5(3-carboxymethoxyphenyl)-2Htetrazolium (MTT) and inductively coupled plasma-mass spectrometry assays, respectively. In addition, the radiosensitization effects of ZnO NPs were investigated under MV irradiation using a clonogenic survival assay. Apoptosis induction and DNA damage were also evaluated using flow cytometry and cytokinesisblock micronucleus assay, respectively. Results: ZnO NPs were taken up and reduced the viability of the cancer cells at a higher rate compared to the normal cells. Moreover, ZnO NPs significantly enhanced the radiosensitivity of the cancer cells with the sensitizer enhancement ratios of 1.23 and 1.31 at the concentrations of 10 and 20 μg/ml, respectively. However, they had no significant effect on the radiosensitivity of the normal cells. Apoptosis induction and DNA damage also improved at a higher rate in the cancer cells compared to the normal cells with the combination of ZnO NPs with MV radiation. Conclusion: According to the results, ZnO NPs had the potential to be a selective radiosensitizer for lung cancer radiotherapy under MV X-ray irradiation. Some of the cytotoxic and genotoxic mechanisms in radiosensitization by ZnO NPs were elevated apoptosis induction and DNA damage levels.

Research paper thumbnail of Being on the right path

Iranian Journal of Radiation Research, Jun 15, 2005

The 1 st issue of the Iranian Journal of Radiation Research (IJRR) was published two years ago (J... more The 1 st issue of the Iranian Journal of Radiation Research (IJRR) was published two years ago (June 2003). This journal was initiated to bring together the various disciplines of radiation oncology, radiation biology, medical physics, nuclear medicine and other related subjects to intensify the dialogue between basic and clinical researchers especially those working in Iran. Within the last two years, this journal has tried to offer an ideal platform for the exchange of detailed scientific information concerning the latest developments in the field of radiation research, from various institutes, hospitals or even individuals. IJRR has been one of the specialized journals when published 2 years ago. The executive committee of the journal has been anxious about the quality and quantity of papers received by the IJRR office. The reason is that, the research activities in these fields are unexplored. Then, we believed that there might not be sufficient numbers of articles to be published in a specialized magazine as IJRR. Now, only a little over 2 years we have realized potential peoples and centers working in this area, not only in Iran but in other countries who contributed sincerely to the journal so that we are not worried about the materials to be published. We have realized that the existence of such a unique journal is a must both for Iran and the researchers in the region. Shortly after publishing the 1 st issue, we tried to computerize all activities in the editorial office, including online review by our reviewers. The journal's website is one of the most complete websites among Iranian journals with search capabilities and free access to abstracts and full PDF texts by readers and our visitors. The scientific quality of the journal specifically depends on the quality of papers submitted and the keen attention of the journal's reviewers. These efforts were led to recognition of the journal as a scientific and academic research source by the ministry of Health and Medical Education. It has also been indexed by Index Medicus for Eastern Mediterranean Region (IMEMR). And now, in an annual qualification of scientific medical journals, IJRR is ranked among the highest scored journals. We are proud to publish the 3 rd volume of the journal with a short delay. To fulfill the interest of our readers and taking another step toward being internationally published in the field of radiation research, we have made some changes in the structural appearance and reference citation according to Vancouver's format. We would like to express our special thanks to our editorial board for their help and suggestions, all reviewers for their sincere help and careful review of the articles and my colleagues at the editorial and publishing office. I doubt we could publish this journal without their interest and efforts. IJRR is looking forward to receiving the invaluable papers from Iranian and foreigner scientists to be published in the forthcoming issues.

Research paper thumbnail of The Primed In Situ (PRINS) technique: an alternative approach for preimplantation chromosomal diagnosis

Iranian Journal of Biotechnology, Jul 1, 2004

Preimplantation genetic diagnosis (PGD) is a novel approach for the prevention of genetic disorde... more Preimplantation genetic diagnosis (PGD) is a novel approach for the prevention of genetic disorders in couples at risk of having offspring with genetic disease. Although the original idea dates back to early 1960s when sexing of rabbit blastocysts was attempted, the first clinical application of PGD was reported about three decades later, describing the use of PCR for sexing embryos from couples at risk of X-linked disease. The development of PCR-based tests led to PGD for screening well known monogenic diseases such as thalassaemia and cystic fibrosis. The introduction of fluorescence in situ hybridization (FISH) quickly replaced PCR-based methods which had led to misdiagnoses for sexing embryos. FISH can be used for aneuploidy screening of up to seven clinically significant chromosomes and translocation detection. The advent of molecular genetic techniques has brought forth new procedures for in situ chromosomal analysis. One of these techniques is the primed in situ labeling (PRINS) procedure which constitutes a fast and efficient alternative to conventional fluorescence in situ hybridization for nucleic acid detection. This technique has the potential to become a powerful tool for cytogenetic investigations. The recent achievements reported show that PRINS can constitute an efficient complement to PCR and FISH. Adaptation of this technique to preimplantation embryo screening both at chromosomal level and gene localization opens a promising perspective for being used in the field of PGD.

Research paper thumbnail of Induction of DNA damage, apoptosis and micronuclei in peripheral blood lymphocytes following injection of contrast media in patients with abdominal CT scan

International journal of radiation research, Apr 1, 2017

Background: Medical diagnos c procedures such as X-ray and computed Tomography (CT) scan account ... more Background: Medical diagnos c procedures such as X-ray and computed Tomography (CT) scan account for considerable percent of pa ent's exposure to ionizing radia on. The exposure of cells to Ioniza on radia on results in induc on of DNA damage and chromosomal aberra ons. Contrast media (CM) are widely used in diagnos c radiology and CT scan. The aim of this study was to study adverse gene c effects of combined administra on of non ionic contrast media and low dose X-rays in peripheral blood Lymphocytes of pa ents following abdominal CT scan. Materials and Methods: A total of 55 pa ents underwent abdominal CT scan with injec on of non ionic contrast media (30 pa ents with omnipaque 300 mg/ml and 25 pa ents with visipaque 270 mg/ml) as well as 13 pa ents undergoing abdominal CT scan (without contrast), selected as control group, were enrolled in this study. Peripheral blood leukocytes were obtained in heparin containing tubes and cultured for the micronucleus test, or were directly used for apoptosis and DNA damage with the neutral comet assay. Results: The frequency of micronuclei, apoptosis and percentage of DNA damage was increased in most pa ents a5er the injec on of contrast media, significantly different from the control group as compared with the samples obtained before and a5er injec on of contrast media (P<0.05). Conclusion: The present study suggest that non ionic contrast media (omnipaque 300 mg/ml and visipaque 270 mg/ ml) may cause a significant increase of cytogene c damage in peripheral blood lymphocytes. This effect might be caused by the enhancement of radia on dose by CM that eventually may lead to the manifesta on of ill health such as cancer.

Research paper thumbnail of Cellular S-value of beta emitter radionuclide’s determined using Geant4 Monte Carlo toolbox, comparison to MIRD S-values

iranian journal of nuclear medicine, 2016

Introduction: Spatial dose distribution around the radionuclides sources is required for optimize... more Introduction: Spatial dose distribution around the radionuclides sources is required for optimized treatment planning in radioimmunotherapy. At present, the main source of data for cellular dosimetry is the s-values provided by MIRD. However, the MIRD s-values have been calculated based on analytical formula in which no electrons straggling is taken to account. In this study, we used Geant4-DNA Monte Carlo toolbox to calculate s-values and the results were compared to the corresponding MIRD data. Methods: Similar to MIRD cell model, two concentric spheres representing the cell and its nucleus were used as the geometry of simulation. The cells were assumed to be made of water. Cellular s-values were calculated for three beta emitter radionuclides 131 I, 90 Y and 177 Lu that are widely used in radioimmunotherapy. Few lines of code in C++ were added into Geant4-DNA codes to automatically calculate the s-values and transfer data into excel files. The differences between two series of data were analyzed using Pearson's correlation and Bland-Altman curves. We observed high correlation (R 2 >0.99) between two series of data for self-absorption; however, the agreement was very weak and Wilcoxon signed rank test showed significant difference (p-value<0.001). In cross-absorption, Bland-Altman analysis showed a considerable bias between MIRD s-values and corresponding Geant4-DNA data. The percent differences between the data were -79% to +67%. Results of the comparison show a reflection of systematic error rather than statistical fluctuation. The inconsistency is most probably associated with the neglecting of straggling and δ-ray transport in MIRD analytical method.

Research paper thumbnail of A biallelic loss-of-function variant in TMEM147 causes profound intellectual disability and spasticity

Research paper thumbnail of Evaluation of the potential diagnostic role of the Lnc-MIAT, miR-29a-3p, and FOXO3a ceRNA networks as non-invasive circulatory biomarkers in ductal carcinoma breast cancer

Over the last few decades, tremendous progress has been achieved in the early detection and treat... more Over the last few decades, tremendous progress has been achieved in the early detection and treatment of breast cancer. However, the prognosis remains unsatisfactory, and the underlying processes of carcinogenesis are still unclear. The purpose of this research was to find out the relationship between MIAT, FOXO3a, and miRNA29a-3p and evaluated the expression levels of them in breast cancer tissue compared to whole blood and their potential as a noninvasive biomarker in whole blood in breast cancer. Whole blood and breast cancer tissue are taken from patients before radiotherapy and chemotherapy. Total RNA was extracted from breast cancer tissue and whole blood to synthesize complementary DNA (cDNA). The expression of MIAT, FOXO3a and miRNA29a-3p was analyzed by the RT-qPCR method and the sensitivity and specificity of them were determined by the receiver operating characteristic (ROC) curve. Bioinformatics analysis was used to understand the connections between MIAT, FOXO3a, and mi...

Research paper thumbnail of • Editor's Commentary Seven years publication of "Iranian Journal of Radiation Research" with confident but cautious steps

The Iranian Journal of Radiation Research (IJRR) is now in the eighth year of publication. This j... more The Iranian Journal of Radiation Research (IJRR) is now in the eighth year of publication. This journal is the mouth piece of shared idea of Dr Shahram Akhlaghpoor and me, which was established way back in 2002. At that time the main emphasis of the founder members was to make the subject of radiation research attractive and interesting especially for combating cancer and risk assessment. The dream for creating the Journal has come true by the help of Dr Seyed Mahmood Aghamiri who obtained the necessary permission for its publication and the Novin Medical Radiation Institute for financial and logistic supports.

Research paper thumbnail of Investigation of Expression and Methylation Status of ELF5 Gene Promoter in Patients with Breast Cancer

scientific journal of ilam university of medical sciences, 2020