WT-1, BAALC, and ERG Expressions in Iranian Patients with Acute Myeloid Leukemia Pre- and Post-chemotherapy.

Purpose: Acute myeloid leukemia (AML) is the most prevalent acute leukemia in adults. It possesses different cytogenetic and molecular features. The expression of Wilms tumor-1 (WT1), brain and acute leukemia, cytoplasmic (BAALC) and ETS-related gene (ERG) might be considered as prognostic factors in AML patients. The aim of this study was to determine the mRNA expressions of WT-1, BAALC and ERG genes in bone marrow of mononuclear cells and their effects on complete remission in the Iranian AML patients, pre- and post- chemotherapy. Methods: Forty AML patients with normal karyotype were evaluated. The mRNA gene expressions were measured with quantitative real-time PCR in bone marrow of mononuclear cells of AML patients at the baseline and after chemotherapy. The subtypes of AML and flow cytometry panel were also assessed. Complete remission (CR) after the treatment was addressed for all patients. Results: The mRNA expressions of WT-1, BAALC and ERG were significantly decreased after the treatment (p = 0.001, 0.017, 0.036). WT-1 mRNA expression was inversely correlated with CR after chemotherapy (P =0.024). There was also significant correlation between baseline expression of BAALC and CR (P =0.046). No significant correlation was observed between ERG and CR pre- and post- chemotherapy (P =0.464 and 0.781). There was also significant correlation between BAALC mRNA expression and CD34+ (P <0.001). Conclusion: The present study showed that WT-1 decreased significantly after standard chemotherapy which could have favorable effects on CR. Also, the high expression of BAALC could have a poor prognostic role in AML patients. The identification of these gene expressions can be an efficient approach in targeted therapy among AML patients.

Analysis of CTLA-4+49A/G gene polymorphism in cases with leprosy of Azerbaijan, Northwest Iran.

Leprosy, which is developed by the obligate intracellular Mycobacterium leprae (ML); has different manifestations, associated with the host immune responses. The protective immune response against ML includes T-cell-mediated immunity. The CTLA-4 has a great impact as a negative regulator of the immune response and maintenance of peripheral tolerance. This study analyzed the relationship between CTLA-4+49A/G gene polymorphism and clinical manifestation of leprosy disease and susceptibility among the Azeri population living Northwest Iran. One hundred and ninety-two leprosy patients and 185 healthy controls participated in the study. CTLA-4+49A/G genotyping was conducted via tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) analysis. The allelic and genotypic frequencies of +49A/G gene polymorphism were similar in controls and patients. However, older ages, older age of onset and over-representation in male were observed in lepromatous leprosy patient carriers of GG genotype. The current study demonstrates that although CTLA-4+49A/G polymorphism was not correlated with a higher genetic risk for leprosy, the presence of a GG genotype was associated with older ages, older age of onset and over-representation in male in Iranian Azeri population.

Antioxidant Expression Response to Free Radicals in Active Men and Women Fallowing to a Session Incremental Exercise; Numerical Relationship Between Antioxidants and Free Radicals.

BACKGROUND: Energy production is a necessary process to continue physical activities, and exercise is associated with more oxygen consumption and increase of oxidative stress. what seems important is the numerical relationship between antioxidant and free radicals. Although the activity of some enzymes increases with physical activities, but it is possible that gene expression of this enzyme is not changed during exercise. OBJECTIVES: The aim of the present study is to investigate the antioxidant enzymes gene expression and changes in malondialdehyde (MDA) and total antioxidant capacity (TAC) levels in men and women affected by a session of incremental exercise and to carefully and numerically assess the relationship between MDA changes and gene expression and activity of antioxidant enzymes. MATERIALS AND METHODS: 12 active men and 12 active women (21 - 24 years old) participated voluntarily in this study. Peripheral blood samples were taken from the subjects in three phases, before and after graduated exercise test (GXT) and 3 hours later (recovery). RESULTS: The gene expression of manganese superoxide dismutase (MnSOD) enzyme increased significantly in women in the recovery phase (P < 0.05). Catalase gene expression significantly increased in men in both phases (immediately & recovery) (P < 0.05). But the changes in active women were only significant immediately after the exercise. TAC levels increased significantly in men in the recovery phase and in active women immediately after the exercise (P < 0.05). MDA activity also increased significantly in men in both phases (P < 0.05). However, in women the increase was significant only in the recovery phase (P < 0.05). There was a reverse relationship between changes in MnSOD and copper- and zinc-containing superoxide dismutase (Cu/ZnSOD) levels and MDA in men (P < 0.05). In active women there was also a significant relationship between changes in MDA and gene expression of Cu/ZnSOD and TAC (P < 0.05). CONCLUSIONS: The increase in free radicals during incremental exercises challenges gene expression and activity of antioxidant enzymes. However, despite the negative effects of free radicals, in women, activity and gene expression of antioxidant enzymes respond appropriately to free radicals.

Association between two single base polymorphisms of intercellular adhesion molecule 1 gene and inflammatory bowel disease.

AIM: The present study evaluated the association between G241R and K469E polymorphisms of intercellular adhesion molecule 1 gene and inflammatory bowel disease in Iranian population. BACKGROUND: Inflammatory bowel disease including ulcerative colitis and Crohn's disease, is a chronic idiopathic inflammatory disease of the gastrointestinal tract. There are two single base polymorphisms of intercellular adhesion molecule 1gene, G241R and K469E, reported to be associated with inflammatory disorders. PATIENTS AND METHODS: In this case-control study, 156 inflammatory bowel disease patients (110 ulcerative colitis and 46 Crohn's disease patients) and 131 healthy controls were enrolled. Two polymorphisms of intercellular adhesion molecule 1 gene, including G241R and K469E, were assessed by polymerase chain reaction followed by restriction fragment length polymorphism. RESULTS: The E469 allele of K469E polymorphism was significantly more frequent in Crohn's disease patients compared to controls (P< 0.05, OR= 1.83; 95% CI: 1.13 to 2.96). The mutant homozygote genotype of K469E polymorphism (E/E) was also significantly more frequent in Crohn's disease patients compared to controls (P< 0.05, OR= 4.23; 95% CI: 1.42 to 12.59). No difference was observed in the frequency of K469E polymorphism among ulcerative colitis patients compared to controls. There were no significant differences in genotype and allele frequencies of G241R polymorphism among ulcerative colitis and Crohn's disease patients compared to control subjects. CONCLUSION: According to our findings, K469E polymorphism of intercellular adhesion molecule 1 gene may probably participate in the pathogenesis of Crohn's disease in Iran.

Ghrelin Administration Increases the Bax/Bcl-2 Gene Expression Ratio in the Heart of Chronic Hypoxic Rats.

PURPOSE: Programmed cell death or apoptosis, is a biochemical procedure that initiates due to some conditions, including hypoxia. Bax and Bcl-2 are among the agents that regulate apoptosis. The amplification of the first one triggers the initiation of apoptosis, and the second one prevents it. Ghrelin is an endogenous peptide that antiapoptosis is its new effect. The aim of this study is to examine the effect of ghrelin on the Bax/Bcl-2 ratio. METHODS: Twenty four wistar rats were divided randomly in three groups; control, hypoxic + saline and hypoxic + ghrelin. Hypoxic animals lived in O2 11% for 2 weeks and received either saline or ghrelin subcutaneously daily. The bax and Bcl-2 gene expression were measured by Real-Time RT-PCR. RESULTS: Chronic hypoxia increased the Bax gene expression significantly compared with normal animals (P = 0.008), but the Bcl-2 was not affected by hypoxia. The Bax/Bcl-2 ratio also amplified significantly (P=0.005). Ghrelin administration significantly increased the Bax/Bcl-2 ratio in the hypoxic animals compared to the hypoxic + saline and normal groups (p=0.042 and P= 0.001, respectively). CONCLUSION: In the present study, animals' treatment with ghrelin leads to an increment of Bax/Bcl-2 ratio, which indicates a controversy related to cardioprotection of ghrelin.

Investigation of IL-21 gene polymorphisms (rs2221903, rs2055979) in cases with multiple sclerosis of Azerbaijan, Northwest Iran.

BACKGROUND: Multiple Sclerosis (MS) is a chronic inflammatory demyelinating disease of the Central Nervous System that is immunologically mediated in genetically susceptible individuals. IL-21, a cytokine produced by TCD4(+) cells, particularly by Th-17 cells, is believed to play an important role in the MS pathogenesis. OBJECTIVE: This study was performed to investigate the impact of genetic polymorphisms in IL-21 gene on MS susceptibility and clinical profiles. METHODS: Seventy Iranian patients with clinically definite relapsing-remitting MS and 110 age, sex and ethic matched controls were genotyped for IL-21 gene polymorphisms using PCR-RFLP method. RESULTS: Our results showed that the IL-21 rs2221903 SNP is not polymorphic in our population. Also, the allelic and genotypic frequencies of the IL-21 rs2055979 did not differ significantly between the MS patients and controls (P = 0.413 and P = 0.565 respectively, and OR = 1.122, 95% CI = 0.79-1.87 for T allele). However, our results showed that IL-21 rs2055979 (G/T) T allele positive (TT+GT) MS patients had lower (PI ≤ 1.5) disease progression compared to rs2055979 T allele negative (GG) patients (P = 0.009). CONCLUSION: Our results showed that no outstanding association exists between IL-21 alleles and susceptibility to MS. However, our clinical analysis showed significant association of IL-21 gene polymorphism with the progression of multiple sclerosis disease. Our results indicate that the G allele promotes, or the T allele protects against disease progression. To clarify the role of IL-21 rs2055979 in MS pathogenesis, further comprehensive studies with larger sample sizes among different ethnicity populations are recommended.

Investigation of CTLA-4-318C/T gene polymorphism in cases with type 1 diabetes of Azerbaijan, Northwest Iran.

This study analyzed the association of CTLA-4-318C/T gene polymorphism with susceptibility, clinical course and laboratory findings of Type 1 diabetes (T1D). One hundred and fifty-three T1D patients and 189 healthy controls entered this study. CTLA-4-318C/T genotyping was performed by tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) analysis. The allelic and genotypic frequencies of -318C/T gene polymorphism were similar in patients and controls. However, younger age, earlier age at onset, higher HbA1c levels, higher frequency of Glutamic acid decarboxylase antibodies (GADA) and Insulinoma Associated-2 Autoantibodies (IA-2A) were observed in T1D patient carriers of CT genotype. The current study demonstrates that although CTLA-4-318C/T polymorphism was not linked with a higher genetic risk for T1D, the presence of a CT genotype was associated with a younger age of onset, poor control of HbA1c level and positive anti-GAD or IA-2 serum autoantibodies in Iranian Azeri population.

Comparison of immunofluorescence and enzyme-linked immunosorbent assay and immunoglobulin G avidity techniques for screening of anti: Toxoplasma antibodies among single serum sample pregnant women in Tabriz, Iran.

BACKGROUND: Congenital toxoplasmosis is that pregnant women acquire the infection during gestation; diagnosis of the acute infection during pregnancy is a complex subject of maternal toxoplasmosis. Thus, the presence of immunoglobulin G (IgG) and/or IgM Toxoplasma antibodies in a single serum sample drawn during gestation cannot be used to define whether the infection was recently acquired or chronic. MATERIALS AND METHODS: At this cross-sectional descriptive study, sera of 391 pregnant women examined and compared. They were in an age range of 21-35 years, referred by gynecologists and infectious disease specialists, during March 2012-April 2013. They have referred, 215 (54.98%), 102 (26%), 74 (18.92%) in the first, second and third trimesters of gestation, respectively. For each of them, a questionnaire was completed and serum samples were prepared in an equal condition, examined according to the procedures of indirect immunofluorescence (IIF), enzyme-linked immunosorbent assay (ELISA) and IgG Avidity techniques. RESULTS: We have found 111 (28.38%) seronegative and 280 (71.61%) seropositive cases by IIF and 124 (31.70%) seronegative, 267 (68.28%) seropositive cases by ELISA. The IgG avidity test confirmed 45 (69.23%) and 7 (10.76%) doubtful cases of IgM test in IIF and ELISA techniques. CONCLUSIONS: This study highlights how to manage pregnant women with toxoplasmosis, especially in a single serum sample condition.

The role of Th17 cells in patients with relapsing-remitting multiple sclerosis: interleukin-17A and interleukin-17F serum levels.

BACKGROUND AND AIMS: Multiple sclerosis (MS) is an inflammatory condition of the central nervous system, with genetic and environmental factors having a role in its etiology. The condition is characterized by demyelination, acute inflammation, and chronic and acute lesions in the central nervous system. Human and experimental studies have shown that T-helper cells, and pro-inflammatory cytokines have a major role in the pathogenesis of MS. Recent researches have shown that IL-17 secreting T (Th17) cells have a role in inflammation and demyelination of the central nervous system. In the present study, the role of Interleukin-17A (IL-17A) and Interleukin-17F (IL-17F) in the immunopathogenesis and follow-up of the MS disease was evaluated. MATERIALS AND METHODS: Thirty-five relapsing remitting (RR) form of MS patients were included in the present study. Blood samples were taken from 35 MS patients and 35 healthy individuals as controls. Enzyme-Linked Immunosorbent Assay (ELISA) was used to determine IL-17A and IL-17F serum levels. RESULTS: A statistically significant increase was noted in the serum levels of IL-17A and IL-17F in MS patients compared to the controls (P<0.001). There was a significant positive correlation of IL-17F serum levels with the number of relapses (rs=0.717, P<0.001). However, there was no significant relationship between the serum levels of these cytokines and Expanded Standard Disability Stated Scale (EDSS) and disease Progression Index (PI). CONCLUSION: The data of the present study revealed a significant increase in the serum levels of IL-17A and IL-17F in MS patients compared with healthy controls and a significant positive correlation of IL-17F serum levels with the number of relapses. It appears that increased serum levels of IL-17 and especially IL-17F may lead to a raised risk of MS.

New Approaches to the Immunotherapy of Type 1 Diabetes Mellitus Using Interleukin-27.

Type 1 diabetes (T1D) is a pancreatic beta cell specific autoimmune disease. One of the most significant current discussions in T1D studies is therapy. Since the conventional therapy, islet transplantation and external insulin, e.g., cannot prevent the destructive autoimmune process against original beta cells and persistent hyperglycemia remains, so recent developments in the field of T1D therapy paved the way to a renewed interest in immunotherapy based on the disease process, especially monoclonal antibody therapy. Due to encouraging laboratory results, cytokine antibody-based drugs could be effective in the clinical direction of the T1D disease process. Hence, implementation of this approach can be useful to improve clinical and laboratory manifestations of T1D.

Analysis of PTPN22 C1858T gene polymorphism in cases with type 1 diabetes of Azerbaijan, Northwest Iran.

BACKGROUND: Type 1 diabetes (T1D) is a T-cell mediated autoimmune multifactorial disease. The PTPN22 gene encodes an intracellular lymphoid-specific phosphatase (Lyp) that has been shown to play a negative regulatory role in T cell activation. OBJECTIVES: The aim of the present study was to find out associating the PTPN22 C1858T (R620W) polymorphism and T1D in the Azeri population from Northwest Iran. SUBJECTS AND METHODS: One hundred and forty-four T1D patients and 197 healthy controls entered this study. We used restricted fragment length polymorphism (RFLP) method to type PTPN22 C1858T polymorphism. RESULTS: There was no significant difference in distribution of genotype and allele frequencies of PTPN22 C1858T polymorphism between T1D patients and controls (P=1.000 for both comparisons and OR=0.91, 95% CI=0.25-3.26 for 1858T allele). However, T allele frequency was significantly increased in T1D patients with Hashimoto's thyroiditis (5.77%) compared with T1D only (0.43%, P=0.019). Moreover, there were no significant differences between studied parameters (including gender, age at onset and family history of T1D) and different genotypes of 1858 PTPN22 C/T polymorphisms in patients. Data showed a low frequency of the minor (T) allele by 1.4% in T1D and 1.5% in healthy individuals. CONCLUSIONS: The PTPN22 C1858T is not relevant in susceptibility to T1D in the Azeri population of Northwest Iran. Our data also indicate that T1D carriers of the T1858 allele could be at enhanced risk for other comorbid autoimmune disorders.

The prostaglandin synthase 2/cyclooxygenase 2 (PTGS2/ COX2) rs5277 polymorphism does not influence risk of colorectal cancer in an Iranian population.

BACKGROUND: The prostaglandin-endoperoxide synthase 2 [PTGS2, commonly known as cyclooxygenase-2 (COX-2)] is an enzyme induced by proinflammatory stimuli that is often overexpressed in malignant tissue and involved in the synthesis of prostaglandins and thromboxanes, regulators of processes such as inflammation, cell proliferation, and angiogenesis, all relevant for cancer development. We investigated whether a functional genetic polymorphism, rs5277, in COX-2 may have a risk-modifying effect on sporadic colorectal cancer in an Iranian population. MATERIALS AND METHODS: We conducted a case-control study on 167 patients with colorectal cancer and 197 cancer-free controls in Taleghani Hospital in Tehran, Iran, between 2007 and 2011. Peripheral blood samples of both groups were processed for DNA extraction and genotyping of the COX-2 gene polymorphism (rs5277) using PCR-RFLP. RFLP results were confirmed by direct sequencing. Logistic regression analysis was performed to calculate the adjusted odds ratio (OR) and 95% confidence interval (95% CI). RESULTS: There was no significant difference in the distribution of COX-2 gene rs5277 polymorphism genotype and the allelic form, among CRC patients compared with the healthy control group (p: 0.867). CONCLUSIONS: Our results suggest that rs5277 polymorphism in COX2 could not be a good prognostic indicator for patients with CRC.

Aberrant phenotype in Iranian patients with acute myeloid leukemia.

PURPOSE: The aim of this study was to evaluate the incidence of aberrant phenotypes and possible prognostic value in peripheral and bone marrow blood mononuclear cells of Iranian patients with AML. METHODS: 56 cases of de novo AML (2010-2012) diagnosed by using an acute panel of monoclonal antibodies by multiparametric flowcytometry. Immunophenotyping was done on fresh bone marrow aspirate and/or peripheral blood samples using the acute panel of MoAbs is stained with Phycoerythrin (PE) /fluorescein isothiocyanate (FITC), Allophycocyanin (APC) and Peridinin-chlorophyll protein complex (perCP). We investigated Co-expression of lymphoid-associated markers CD2, CD3, CD7, CD 10, CD19, CD20 and CD22 in myeloblasts. RESULTS: Out of the 56 cases, 32 (57.1%) showed AP. CD7 was positive in 72.7% of cases in M1 and 28.5% in M2 but M3 and M4 cases lacked this marker. We detected CD2 in 58.35 of M1cases, 21.40% of M2 cases, 33.3 of M3 and 20% of M5; but M4 patients lacked this marker. The CBC analysis demonstrated a wide range of haemoglobin concentration, Platelet and WBC count which varied from normal to anaemia, thrombocytopenia to thrombocytosis and leukopenia to hyper leukocytosis. CONCLUSIONS: Our findings showed that CD7 and CD2 were the most common aberrant marker in Iranian patients with AML. However, we are not find any significant correlation between aberrant phenotype changing and MRD in our population. Taken together, this findings help to provide new insights in to the investigation of other aberrant phenotypes that may play roles in diagnosis and therapeutic of AML.

Does Chemotherapy Change Expression of VEGF A&C and MVD in Acute Myeloid Leukemia?

INTRODUCTION: Acute Myeloid Leukemia is a malignant transformation of hematopoietic tissue, bone marrow infiltration of undifferentiated cells known as blasts that interfere with the production of normal cells. Vascular endothelial growth factor (VEGF) is persistently secreted from myeloid cells and high levels can be detected in patients' serum. METHODS: Twenty-one AML patients, who were chemotherapy candidates were evaluated in a clinical trial. Serum VEGF was measured by ELISA. VEGFA, VEGFC mRNA and bone marrow MVD were measured in all patients before and after chemotherapy and then all results were analyzed. RESULTS: There were 10 (48%) female and 11(52%) male patients ranged in age from 20 to 60 years, with an average age of 39.5 ±14.1 years. The mean amount of MVD was reduced from 10.8±3.6 before chemotherapy to7.6±3.3 after chemotherapy (P=0.008). VEGF was also reduced from 0.59±0.16 before chemotherapy to 0.24±0.03 after chemotherapy (P=0.005). Gene expression differences for VEGFA mRNA was 4.6±1.4, while it was 120.7±93.2 for VEGFC mRNA, showing the significance only for VEGA mRNA (P=0.02). CONCLUSION: Regarding reduced angiogenesis, we can conclude that anti-angiogenic preparations can be effective in treatment course of AML in combination with chemotherapy regimen.

Association of IL-13 single nucleotide polymorphisms in Iranian patients to multiple sclerosis.

MS is an autoimmune disease and interleukin 13 (IL-13) has been proposed to be an important neuroprotective mediator in MS. Because of plausible effect of single nucleotide polymorphisms (SNPs) in expression level or biological activity of any cytokine, we sought to investigate association of IL-13 SNPs, C-1112T, A-1512C and G+2044A, with risk to MS. Sixty-eight RRMS patients and 110 healthy controls were involved in this study. After extraction of genomic DNA, frequency of genotypes and alleles were determined by PCR-RFLP and data were analyzed statistically. Results showed significant higher frequency of CC, CC, and AA genotypes and C, C, and A alleles of -1112CT, -1512AC and +2044GA SNPs respectively, in patients group. There was significant association between -1112C allele with onset age of MS. No significant association was seen between any of genotypes or alleles with expanded disability status scale (EDSS) of patients. Our findings showed significant association between three studied SNPs of IL-13 with susceptibility to MS in Iranian patients. More studies should be done on other IL-13 SNPs, and also polymorphisms of IL-13 receptor and other cytokines to determine the exact role of SNPs in protecting or predisposing of individuals for MS.

Quantitative evaluation of CXCL8 and its receptors (CXCR1 and CXCR2) gene expression in Iranian patients with multiple sclerosis.

CXCL8 and its receptors (CXCR1 and CXCR2) play important roles in CNS development, neuronal survival, modulation of excitability, and neuroimmune response. The aim of this study is to evaluate gene expression of CXCL8 and CXCR1/CXCR2 in peripheral blood cells (PBCs) of Iranian patients with relapsing remitting (RR) form of Multiple sclerosis (MS). We explored the mRNA expression of CXCL8 and its receptors in PBCs of 49 RR-MS patients in remitting status and 60 healthy controls by quantitative Real-Time PCR. Median expression of CXCL8 mRNA in peripheral blood of MS patients decreased more than 3-fold compared to control group (p < 0.001), while there were not significant differences in CXCR1 and CXCR2 gene expression between MS patients and healthy subjects (p = 0.159 and p = 0.248, respectively). There was a significant negative correlation of CXCR2 expression with EDSS (rs = -0.432, p = 0.004). It appears that decreased expression of CXCL8 may lead to a raised risk of MS.

Penbactam for Helicobacter pylori eradication: a randomised comparison of quadruple and triple treatment schedules in an Iranian population.

BACKGROUND & STUDY AIMS: Selection of the best drug regimens for eradication of Helicobacter pylori infection especially in patients at risk of peptic ulcer relapses and the development of complications is challenging. This study assessed and compared the efficacy of the two common PPI based triple therapies to a quadruple therapy including PPI, metronidazole, amoxicillin and a bismuth compound in Iranian population. PATIENTS & METHODS: Three hundred and thirty patients with peptic ulcer and H. pylori infection were included in the study. Patients were randomly assigned to one of the three treatment protocols all given twice daily: (a) A 14-day quadruple therapy (OMAB group) comprising omeprazole 20mg, metronicazole 500 mg, amoxicillin 1g, and bismuth subcitrate 240 mg; (b) A 14-day triple regimen (OCP group) comprising omeprazole 20mg plus clarithromycine 500 mg and penbactam 750 mg and (c) A 14-day triple regimen (OCA group) comprising omeprazole 20mg plus clarithromycine 500 mg and amoxicillin 1g. Cure was defined as a negative urea breath test at least six weeks after treatment. RESULTS: The per-protocol eradication rates achieved with both OCP regimen (87.0%) and OCA treatment (90.8%) were significantly higher than the OMAB treatment protocol (56.0%); however, no significant difference emerged in eradication rates between the two triple treatment schedules. No significant differences between the groups were found in most side-effects. CONCLUSION: Two-week quadruple therapy showed a lower eradication rate compared to common triple treatment schedules when used as first-line eradication treatment for H. pylori infection in Iranian population.

Gene Expression of VEGF-A and VEGF-C in Peripheral Blood Mononuclear Cells of Iranian Patients with Acute Myeloid Leukemia.

OBJECTIVE: The crucial role of angiogenesis in the pathophysiology of acute myeloid leukemia (AML) has been proposed. One of the key regulators of angiogenesis is the vascular endothelial growth factor (VEGF). Among the VEGF family, it has been observed that VEGF-A and VEGF-C are expressed by AML cells and mediate leukemic cell proliferation, survival, and resistance to chemotherapy. Emerging evidence, however, suggests that elevated levels of VEGF or a proangiogenic phenotype may impede, rather than promote, early tumor development and progression. As the significance of VEGF-A and VEGF-C levels in the pathogenesis of AML has not been clarified well, the aim of this study is to evaluate gene expression of these angiogenesis promoters and its possible prognostic value in peripheral blood mononuclear cells of Iranian patients with AML. MATERIALS AND METHODS: We investigated the mRNA expression of VEGF-A and VEGF-C in peripheral blood mononuclear cells of 27 patients with newly diagnosed AML and 28 healthy controls by quantitative real-time PCR. RESULTS: Expression of VEGF-C mRNA was significantly lower in AML patients than in healthy controls (p<0.001). However, there was no significant decrement in expression of VEGF-A mRNA of AML patients compared to the control group (p=0.861). VEGF-A and VEGF-C expression were not able to predict clinical outcome. CONCLUSION: Our data showed that AML is associated with a decreased expression of VEGF-C mRNA. However, expression levels did not influence the clinical outcome in our study. It seems that angiogenesis is affected by different cytokines other than VEGF-C or VEGF-A, and VEGF is also affected by different cytokines. Taken together, these findings help to provide new insights into the investigation of other angiogenic factors and cytokines that may play roles in the pathogenesis of AML. CONFLICT OF INTEREST: None declared.

Protein tyrosine phosphatase non-receptor type 22 gene polymorphism C1858T is not associated with leprosy in Azerbaijan, Northwest Iran.

BACKGROUND: Leprosy (Hansen's disease) is a human chronic granulomatous infectious disease caused by Mycobacterium leprae. Several types of study support a role for host genetics in susceptibility to leprosy. The protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene encodes an intracellular lymphoid protein tyrosine phosphatase that has been shown to play a negative regulatory role in T-cell activation. AIMS: The aim of the present study was to find out associating the PTPN22 C1858T (R620W) polymorphism and leprosy in the Azeri population from Northwest Iran. MATERIALS AND METHODS: A total of 153 treated leprosy patients and 197 healthy and ethnic matched controls entered this study. We used restriction fragment length polymorphism method to type PTPN22 C1858T polymorphism. RESULTS: There was no significant difference in distribution of genotype and allele frequencies of PTPN22 C1858T polymorphism between leprosy patients and controls (P = 0.641 and 0.645; respectively). Moreover, there was no significant association between different clinical findings (karnofsky performance status score, clinical forms and manifestations of leprosy) and PTPN22 C1858T polymorphism. Data showed a low frequency of the minor (T) allele by 2.3% in leprosy and 1.5% in healthy individuals. CONCLUSIONS: The PTPN22 C1858T (R620W) is not relevant in susceptibility to leprosy in the Azeri population of Northwest Iran.

Molecular analysis of imperative polymorphisms of MLH1 gene in sporadic colorectal cancer.

BACKGROUND: Single nucleotide polymorphisms in mismatch repair genes may be associated with different protein expression, production, and efficiency according to allele status and influence the risk of developing colorectal cancer. OBJECTIVE: This research aimed at analyzing two important polymorphisms in MLH1 gene and their association in colorectal cancer susceptibility. METHODS: In total, 219 CRC patients and 248 healthy controls were genotyped with PCR/RFLP for I219V and IVS12-169 C>T polymorphisms in MLH1 gene. Sequencing performed to ensure work flow and results. We used unconditional logistic regression after adjusting for age and sex to evaluate the association between each polymorphism and colorectal cancer. RESULTS: The MLH1 I219V polymorphism was associated with colorectal cancer susceptibility (P=0.01). Stratified data analysis for gender demonstrated association of AG (P=0.009) and GG (P=0.021) genotypes with risk of colorectal cancer in women. In contrast there is no association with IVS 12-169 C>T polymorphism and colorectal cancer risk. CONCLUSIONS: I219V SNP might be a susceptibility factor for CRC and gender is a factor that must be considered when it is analyzing. Further tests need to be done to define it as a dependable prognosis factor.