فصلنامه خون
سال یازدهم شماره 2 (پیاپی 44، تابستان 1393)

The low frequency of hematopoietic stem cells in umbilical cord blood is the main factor of its application to be restricted for transplantation. If hematopoietic and mesenchymal stem cells of placenta can be isolated and transplanted with cord blood cells, the problem of cell dose limitation will be solved due to increase in the number of primary hematopoietic stem cells and homing of cells through mesenchymal stem cells. Thus in this study, we tried to isolate the maximum number of hematopoietic and mesenchymal stem cells from placenta by enzymatic methods and evaluate their properties. Five different placenta tissues were treated with collagenase and their red blood cells were omitted with the lysis buffer; then, the remaining cells were studied for the presence of hematopoietic and mesenchymal stem cells. The result showed that 6.02 ± 0.6 and 4.78 ± 0.8 percent of isolated cells were CD34+ and CD34+ together with CD38-, respectively. These cells having generated all hematopoietic lineages and adherent stromal cells with the property of mesenchymal stem cells were obtained from the culture of placenta cells. The presence of a remarkable number of CD34+ cells and mesenchymal stem cells in placenta tissue showed that transplantation of these cells with umbilical cord blood cells can increase the quality of transplantation.

The important reason of drug resistance is ATP dependent pumps such as MDR1 that extrudes drugs from the cell. MDR1 is highly polymorphic. It seems that polymorphisms influence the gene expression and response to treatment. The aim of this study was to investigate G2677T/A polymorphism of the MDR1 gene and its association with the response of treatment in childhood acute lymphoblastic leukemia. In this descriptive study, G2677T/A polymorphism of MDR1 was investigated in 44 children with acute lymphoblastic leukemia and 40 healthy individuals by the ARMS-PCR technique. The association of this polymorphism with response to treatment was also investigated. In the patient group, the frequencies of genotypes were 36.4% for TT, 41% for GT, 13.6% for GG,4.5% for AG, 2.25% for AT and 2.25 % for AA whereas in the control group the frequencies were 35%, 37.5%, 10%, 7.5%, 5%, and 5% for TT, GT, GG, AG, AT, and AA, respectively. There was no significant difference in the frequencies of G2677T/A polymorphism between patients and the healthy group. Neither was there any significant difference between the frequency rates of G2677T/A polymorphism of MDR1 in the responder and the non responder. It seems that there is no correlation between G2677T/A polymorphism of MDR1 gene and response to treatment. So the role of G2677T/A polymorphism in the gene expression of MDR1 in childhood acute lymphoblastic leukemia and response to treatment is still controversial.

Bleeding tendency in obligate carriers of hemophilia A has been found since several years ago; some of haemophiliacs with factor levels of 40-60% also have abnormal bleeding. The present study is to measure factor VIII and von Willebrand levels and evaluate their correlation with clinical finding in obligate carriers. In this cross-sectional study conducted 49 obligate carriers of Haemophilia A. F.VIII, vWF: Ag, PT, and APTT levels were checked and their correlationship with the bleeding score was evaluated and analyzed. Fourty-Nine Obligate carriers included in the study. The mean of PT, PTT, F.VIII, vWF: Ag and bleeding score (BS) were 12.6 ± 1.3, 36.3 ± 4.2, 52.5 ± 22.6, 83.7 ± 35.2, and 1.5 ± 1.7, respectively. The present study showed only 4% (2) of the carriers having had bleeding score (BS) equal to 5 and higher. Only F.VIII / vWF: Ag positively correlated with BS significantly (p = 0.006). The present study showed that PT, PTT, and F.VIII levels and the bleeding score alone could not be helpful in screening obligate carriers. It seems that only determination of F.VIII/vWF: Ag ratio be helpful hn carrier states. But definitive diagnosis carrier states is by molecular genetic testing.

The efficacy of arsenic trioxide (ATO), as a poisonous drug, in the treatment of acute promyelocytic leukemia (APL) is widely accepted. Due to adverse effects associated with high-dose ATO, the combination therapy is a rational therapeutic strategy to enhance the effectiveness of ATO. In this regard, we used simvastatin (SV), a cholesterol lowering medication, and hypothesized that SV plus ATO would potentiate the efficacy of ATO at lower doses. To evaluate the effects of SV and ATO treatment (in isolation or in combination) on transcriptional levels of Bax and Bcl-2, apoptosis, growth kinetic, and metabolic activity of NB-4 cells, we employed RQ-PCR, flowcytometry, trypan blue dye exclusion, and MTT assays, respectively. The data were analyzed using SPSS 21, student’s t-test and one-way ANOVA tests. Both SV and ATO considerably hindered the metabolic activity of NB-4 cells in a concentration-dependent manner. In addition, the co-treatment with them exerted an indicative decline in viability, and a significant augmentation in apoptotic population and in the ratio of Bax to Bcl-2 mRNA level. Our results have demonstrated that ATO and SV cooperate synergistically to induce cell death and to inhibit the proliferation rate of NB-4 cells. Furthermore, our results suggest that the combination treatment increased the programmed cell death rate probably through enhancing the intrinsic mitochondrial apoptotic pathway. On aggregate and in view of these data, SV showed the potency for attenuating the effective dose of ATO.

Breast cancer cells can be hidden from immune cells by shedding tumor markers such as HER2. The increased soluble HER2 (sHER2) concentrations are associated with the outcome of HER2-positive breast cancer and sensitivity to trastuzumab treatment. To this end, camelid single domain antibodies (VHH) with unique properties and binding ability are very striking targeting agents to detect sHER2. By panning on HER2 negative and positive cells, an immune camel library was enriched against HER2 antigen. Affinity and specificity of four selected VHHs to HER2, detection of sHER2 and binding of selected VHHs to HER2 on breast cancer cells were investigated by ELISA. After cell panning and ELISA, four VHHs that recognized HER2 antigen better than negative control were identified. High affinity HER2 specific VHHs (1012-1013 M-1) were able to detect sHER2 (2 µg/ml). When the mixture of VHH and sMUC1 was added to HER2 coated-well, the VHH bound to HER2. RR4 and RR6 VHHs showed the highest binding to SKBR3 (HER2 expressing cell) (2 ± 0.33 and 2.5 ± 0.15, respectively) compared to HER2 negative cell (0.38 ± 0.17 and 0.4 ± 0.12, respectively). The HER2 status of a primary tumor and responses to treatment can be evaluated by measuring sHER2 as a biomarker by HER2 specific VHHs.

One of the common epigenetic pathways in all types of human haematopoeitic neoplasms is the hypermethylation promoter of tumor suppressor genes. It is usually associated with inactivation of the involved genes, and can be reversed using demethylating agents. The aim of this study was to evaluate the frequency of P15 promoter methylation in Iranian acute myeloid leukemia (AML) patients. Furthermore, this study examined the correlation between P15 promoter methylation and P15 expression. P15 promoter methylation has been investigated in 59 acute myeloid leukemia (AML) patients by melting curve analysis. P15 mRNA expression has been analyzed using real-time PCR technique (∆∆CT computational) to investigate the correlation between P15 expression and P15 promoter methylation. The aberrant methylation of the P15 promoter was detected in 40.7% of all patients. Regardless of the methylation pattern, 92.9% of all patients showed a decrease in expression of P15. Out of the total number of patients, 90.9% who showed methylation of P15 gene (22 of 24) and 88.5% (31 of 35) who did not, both illustrated reduction in P15 expression level. Despite the methylation of P15 at a low expression level in most of the patients, no significant difference between methylated and unmethylated groups was observed.

Bakground and Chronic illness and its treatment have negative impact on physical, psychological, and social aspects of quality of life. The purpose of this study was to determine the relationship between spiritual well-being with quality of life and mental health in young adults with beta- thalassemia major. This is a descriptive-correlational study in which ninety six young thalassemics were selected by convenience sampling method from centers for special diseases and Adult Thalassemia Center of Zafar in Tehran. The data werer collected by self-report. The instruments used included the demographic data form, the short form of WHO quality of life (WHOQOL-BREF), the 28- item general health questionnaire (GHQ-28), and the spiritual health questionnaire. The data were analyzed by SPSS version 18 using descriptive statistics, t- test, ANOVA, and pearson coefficient correlation. The findings indicated that 74% had moderate spiritual well-being, 72.9% moderate quality of life, and 62.5% mental health disorder. There was a positive correlation between the score of spiritual well-being and the total score of quality of life (r= 0.347 p= 0.001) and a negative correlation with the score of mental health (r = -0.525 p < 0.001). The increase in the spiritual well being of thalassemia patients is associated with a better quality of life and mental health. It is recommended that the spiritual dimension along with physical, mental, and social dimensions of patients be considered for the holistic nursing care to be properly exerted.

The aim of this quasi-experimental study is to investigate the effect of 6 weeks of progressive endurance training and Silymarin supplementation intake on hematological parameters in sedentary men (age: 25 ± 5 years, weight 86 ± 21, height 178 ± 13, BMI 27 ± 5). To this end, twenty-one students from Shahrood University of Technology who were willing to participate in the study were chosen for the study. The subjects were then randomly divided into supplemental groups (n=11) and placebo groups (n=10). Both groups received progressive endurance training. The control group received placebo while the experimental or supplemental group received Silymarin. Blood samples were collected before and after 6 weeks of exercise training and supplementation intake. Hematological parameters such as RBC, MON, RBC, HCT, PLT were measured. Data were then analyzed using repeated measure (2×2). Hematological parameters such as RBC, MON, RBC, HCT, PLT were measured. Data were analyzed using repeated measure (2×2). The results of this study showed that Silymarin supplementation and progressive endurance training not only increases hemoglobin factor but also reduces monocytes, erythrocytes, and hematocrit factors significantly (P≤0.05).

It is more than 5 decades that hematopoietic stem cell transplantation (HSCT) has been used for treatment of hematologic malignancies, metabolic disordes, and immunodeficiencies. (HLA)-matched HSCT is commonly the preferred type of transplantation, with HLA-matched sibling donors usually the first choice. If there is no related HLA-matched donor, unrelated matched donors are considered. The present article shows the importance of unrelated stem cell donor registries, related regulations and policies, HSCT history, the importance of donor-recipient HLA matching to GVHD inhibition, several donor selection measures, establishment requirements of such registries in the world and Iran, using 29 different references in order to introduce these centers to interested researchers. These Registries rely on positive feelings of unrelated donors to altruistic donation to save patients. Registries from different countries joined and established world and international donor associations and groups to facilitate finding a suitable donor and improve the HSCT outcomes from unrelated donors. Huge progress has been made since the first HSCT to save many patients indebted to the efforts of a few pioneers, group collaborations, and international exchanges of stem cell practiced by international organizations which follow definite standards.