Background and purpose: Prostate cancer is the most prevalent non-cutaneous malignancy in men. The Gleason grading system is an important prognostic factor in prostatic carcinoma. Nowadays, identifying biomarkers indicating high-risk patients and targeted therapy is considered. The CD38 is a membranous glycoprotein involved in adenosine generation, and in this way, it plays a role in tumorigenesis and progression of various tumors. Therefore, this study aimed to evaluate the relationship between CD38 expression and Gleason score in prostatic carcinoma. Materials and methods: In this cross-sectional retrospective study, 85 paraffin blocks from prostatic carcinoma tissue samples were immunohistochemically stained by CD38 monoclonal antibody. The percentage of CD38 expression in tumor cells was determined, and its relation with primary and secondary Gleason grade and total Gleason score in evaluated samples was analyzed by SPSS (version 16). Results: The mean of evaluated patients’ age was 70.67 ± 8.84 years, and 40% were in the range of 71-80 years. The mean of CD38 expression percentage in prostatic carcinoma tumor cells was %49.18 ± 16.58 and in the range of 8%-84%. A significant reverse relationship was found between CD38 expression percentage with primary Gleason grade (P<0.001), secondary Gleason grade (P=0.002), and total Gleason score (P<0.001). Conclusion: It seems that the loss of CD38 expression plays a role in the development, progression, and aggressive behaviour of prostatic carcinoma. Therefore, it is possible that treatments inducing CD38 expression in tumour cells of prostatic carcinoma could effectively treat and prevent tumour progression.

Introduction: CLL is one of the most common leukemias, which is categorized by the accumulation of mature CD5+ B-lymphocytes in the peripheral blood, bone marrow, and secondary lymphoid organs. In this study, the status of rs6449182 polymorphism of the CD38 gene and its association with clinical and laboratory parameters of CLL patients was evaluated. Methods: Genomic DNA extraction was performed using the salting out method. The CD38 gene polymorphism (rs6449182) was studied in 70 patients with CLL and 70 healthy individuals using the PCR-RFLP method. Results: The results of this study showed that the control group had 86% wildtype rs6449182 (CC), 12% heterozygous (CG), and 2% homozygous (GG) genotypes. In the case group, 62% had wild-type genotype (CC) 26% were heterozygous (CG), and 12% were homozygous (GG). Statistical analysis showed that the heterozygous genotype for the CD38 gene was significantly associated with CLL. It was also understood that this polymorphism had a significant relationship with hemoglobin, age, and organomegaly of patients. Conclusions: The CD38 gene polymorphism of rs6449182 SNP G allele had the highest frequency. Moreover, based on the results, this polymorphism has a significant relationship with organomegaly, which indicates the importance of these markers in the pathogenesis and prognosis of the disease.

Background and purpose: Chronic lymphocytic leukemia (CLL) is the most common form of adult leukemia characterized by the accumulation of seemingly mature type B lymphocytes in peripheral blood and lymphatic organs. One of the main markers used in the diagnosis and prognosis of CLL is the CD38 gene. Polymorphism is considered to be a major genetic source of phenotypic change within a species and may be involved in developing the disease. Here, the study of CD38 gene polymorphism (rs 1800561) was done in terms of incidence and relevance to clinical and laboratory parameters in CLL patients. Materials and methods: In order to confirm the CLL disease, CD5, CD19, and CD23 markers were investigated using immunophenotyping. CD38 gene polymorphism was studied in 70 patients with CLL and 70 healthy cases as control using a specific PCR method of polymorphism (Tetra-ARMS-PCR). Statistical analyses were performed in SPSS V18 applying Pearson Chi-Square test. Results: In the patient group, we observed 97% wild-type genotype (CC), 1. 5% heterozygote (CT), and 1. 5 % homozygote (TT). The present study showed that 98. 5% of the control subjects had wild-type (CC) and 1. 5% had heterozygote (CT). The frequency of C and T alleles in both patients and control groups was 97. 9%, 2. 1%, 99. 3%, and 0. 7%, respectively. Conclusion: Based on current study, despite differences in frequency of T and C alleles among patients and healthy individuals, no significant difference was found in the occurrence of this polymorphism and the risk of CLL.

Introduction: CD38 is a multifunctional enzyme with a potent Ca2+ mobilizing effect, cyclic ADP-ribose (cADPR), and nicotinic acid adenine dinucleotide phosphate (NAADP). Here, we aimed to demonstrate the role of CD38 in platelets via protein kinase C (PKC)-mediated internalization and activation. Methods: Mouse platelets were used in this study. Thrombin, an agonist of platelet function, provoked a prompt and long-lasting increase in intracellular Ca2+ concentration ([Ca2+]i), resulting from an interplay of multifold Ca2+ mobilizing messengers. The signaling pathway was delineated using different inhibitors and techniques such as platelet aggregation assay, intracellular calcium measurements, immunoprecipitation, immunoblotting, and flow cytometry. Results: We observed a sequential formation of cADPR and NAADP through CD38 activation by PKC of non-muscle myosin heavy chain IIA (MHCIIA), resulting in phospholipase C (PLC) activation in the thrombin-stimulated platelets. These findings reveal that PKC is fundamental in activating CD38 and elicits a physiological response in the murine platelets. Conclusion: PKC is involved in many signaling pathways. Specifically, PKC is involved in the internalization of CD38 via MHCIIA in CD38+/+ wild-type (WT) and CD38-/-knockout mice (KO). CD38 generates calcium-mobilizing agents that act on specific receptors of the calcium stores. Calcium triggered platelet aggregation while serving as a secondary messenger.

Many investigators have used xenogeneic, especially murine stromal cells and fetal calf serum to maintain and expand human stem cells. The proliferation and expansion of human hematopoietic stem cells in ex vivo culture were examined with the goal of generating a suitable protocol for expanding hematopoietic stem cells for patient transplantation. Using primary fetal liver cells, we established a serum-free culture system to expand human primitive stem/progenitors cells. Non-enriched cord blood CD34+ cells were cultured on a monolayer of mouse primary fetal liver cells in the presence of trombopoietin, flt3/flk2 ligand, and/or stem cell factor, IL-6 and IL-3 under serum-free conditions. After 1 or 2 weeks of culture, cells were examined for clonogenic progenitors and percentage of CD34+ CD38- cells. In the presence of trombopoietin, flt3/flk2 ligand, and stem cell factor, fetal liver cells supported expansion of CD34+ cells more than 10 to 20 fold. In addition, colony forming unit-cell assay was expanded more than 5- and 10-fold after 1 and 2 weeks of culture, respectively. These results strongly suggest that fetal liver cells may be a suitable feeder layer for expansion of hematopoietic progenitors from umbilical cord blood in vitro

Introduction: Umbilical cord blood (CB) has been identified as a rich source for hematopoietic stem cells (HSCs), and has provided an alternative to bone marrow transplantation. The use of ex vivo expanded cells has been suggested as a possible means to accelerate the speed of engraftment in cord blood (CB) transplantation. The main aim of our study is to find the best culture media and condition to increase number of CD34+/CD38- hematopoietic stem cells in cord blood for transplantation.Material and Methods: Mononuclear cells (MNCs) were seperated from cord blood and cultured in RPMI1640 with 10% fetal calf serum (FCS) or 10% cord blood plasma (CBP) or serum free media (SF). Culture media contained 50ng/ml of Interlukin 6 (IL6), IL3, Thrombopoietin (TPO) Stem cell factor (SCF) and flt3-ligand. Cells were cultured for two weeks and number of CD34+/CD38- cells and total MNCs measured at days 0, 7 and 14.Results: At 14 days culture mean fold of expansion of CD34+ and CD34+/CD38- cells was 20.4 and 57.4 for FCS, 5.6 and 10.3 for SF and 10.8 and 4.7 for CBP culture media. Conclusion: Due to efficacy and predictability of SF media for cell expansion and because of its better safety for allergic reactions and microbial contamination (in comparison to animal products containing media) and enough expansion for clinical applications, we suggest that SF media is better than CBP or SF from clinical points of view.

Background: CD38 is highly expressed on multiple myeloma (MM) cells and has been successfully targeted by different target therapy methods. This molecule is a critical prognostic marker in both diffuse large B-cell lymphoma and chronic lymphocytic leukemia.Objective: We have designed and generated an anti-CD38 CAR-NK cell applying NK 92 cell line. The approach has potential application as an off-the-shelf strategy for treatment of CD38 positive malignancies.Methods: A second generation of anti-CD38 CAR-NK cell was designed and generated, and their efficacy against CD38-positive cell lines was assessed in vitro. The PE-Annexin V and 7-AAD methods were used to determine the percentage of apoptotic target cells. Flow cytometry was used to measure IFN-γ, Perforin, and Granzyme-B production following intracellular staining. Using in silico analyses, the binding capacity and interaction interface were evaluated.Results: Using Lentivirus, cells were transduced with anti-CD38 construct and were expanded. The expression of anti-CD38 CAR on the surface of NK 92 cells was approximately 25%. As we expected from in silico analysis, our designed CD38-chimeric antigen receptor was bound appropriately to the CD38 protein. NK 92 cells that transduced with the CD38 chimeric antigen receptor, generated significantly more IFN-γ, perforin, and granzyme than Mock cells, and successfully lysed Daudi and Jurkat malignant cells in a CD38-dependent manner.Conclusion: The in vitro findings indicated that the anti-CD38 CAR-NK cells have the potential to be used as an off-the-shelf therapeutic strategy against CD38-positive malignancies. It is recommended that the present engineered NK cells undergo additional preclinical investigations before they can be considered for subsequent clinical trial studies.

Background and purpose: Chronic lymphocytic leukemia (CLL) is characterized by clonal proliferation and accumulation of long-lived B lymphocytes within the peripheral blood, bone marrow, and secondary lymphoid organs. In this study, immunophenotypic characteristics of leukemic cells and their association with disease prognosis were investigated in CLL patients.Materials and methods: A case-control study was carried out in 25 CLL patients and 15 healthy individuals. Complete blood count was performed for all subjects. CLL patients were classified into different clinical stages based on the Rai staging system. For immunophenotypic characterization of leukemic cells, peripheral blood mononuclear cells (PBMCs) were isolated from CLL patients and stained using specific monoclonal antibodies. They were then analyzed by flow cytometry.Results: The CD5, CD19, CD20, and CD23 were expressed significantly more in advanced clinical stages of CLL compared to those in primary stages (P=0.03, 0.01, 0.02, and 0.02, respectively). The mean fluorescence intensity (MFI) of CD38 in advanced progressive stages of CLL patients was higher than that of primary non-progressive stages (P=0.02).Conclusion: Our results indicated significant immunophenotypic profile and higher CD38 expression in CLL patients with advanced clinical stages. These immunophenotypic characteristics are useful biomarkers for the disease monitoring and therapy.