T-helper Type 1 and 2 Cytokine Levels in Patients with Benign and Malignant Salivary Gland Tumors

ABSTRACT Background: Salivary gland tumors are among malignancies that have high recurrence rate. Immune responses in salivary gland tumors have not been well elucidated. T helper type 1 (Th1) and Th2 cytokines have been reported to play a role in the outcome of head and neck cancers. Objective: To evaluate the serum levels of interferon gamma (IFN-γ), as the hallmark of Th1 cytokines, and interleukin-4 (IL-4), as the hallmark of Th2 cytokines, in patients with benign and malignant salivary gland tumors in comparison with healthy controls. Methods: Fifty patients with benign and 14 patients with malignant salivary gland tumors, as well as 23 healthy individuals were recruited. Serum levels of IFN-γ and IL-4 were measured using ELISA method. Nonparametric tests were used for data analysis. Results: Serum levels of IFN-γ and IL-4 were found not to be significantly different in patients compared to the control group (0.68 ± 0.29 vs. 1.03 ± 0.57 pg/ml, p=0.58 for IFN-γ, 4.57 ± 1.57 vs. 4.41 ± 1.31 pg/ml, p=0.28 for IL-4). IFN-γ and IL-4 serum levels were also not significantly different between patients with benign and malignant salivary gland tumors (p=0.54 and p=0.86, respectively). Conclusion: The systemic levels of IL-4 and IFN-γ seem not to be associated with salivary gland tumor in our study. Investigation of other cytokines produced by Th1 and Th2 cells are warranted

Genetic variation in ACE A2350G: association with reduction in fasting blood glucose after fluoxetine therapy in depressed patients

Various studies have shown that genetic factors contribute substantially to the development and progression of diabetes. Renin-angiotensin system has long been proven to have a major role in cardiovascular physiology and pathology. Its major product Angiotensin II (Ang II) with pro oxidant properties has shown to predict the future risk of diabetes. Fluoxetine, a drug of choice in management of depression, was observed to reduce fasting blood sugar (FBS). In the present study, six common polymorphisms of genes encoding for RAS components were determined in DNAs extracted from venous blood of 100newly diagnosed depressed individuals taking 12 weeks of fluoxetine. Blood samples were collected prior and after the period of treatment in order to measure FBS. Our results indicate that carriers of GG genotype of ACE A2350G showed significantly lower FBS levels after fluoxetine treatment (P=0.043). On the other hand haplotype analysis designate a significant association between DTG carriers of ACE I/D, A-240T and A2350G (P=0.001) and reduced FBS levels. In conclusion, this study supports the hypothesis that RAS genetic variations affect blood glucose after a course of treatment in Iranian population with depressio

Salvurmin A and Salvurmin B, Two Ursane Triterpenoids of Salvia urmiensis Induce Apoptosis and Cell Cycle Arrest in Human Lung Carcinoma Cells

Background: Ursane triterpenoids could be considered as novel multi-target therapeutic anti-cancer agents. Salvurmin A and Salvurmin B are novel cytotoxic ursane triterpenoids isolated from the aerial parts of Salvia urmiensis, an endemic plant species of Iran. Methods: In this study, we assessed cytotoxicity of these compounds against two human cancer cell lines and one human normal cell line and investigated its mechanism via apoptosis and cell cycle arrest. Results: Salvurmin A and B showed the most cytotoxic effect on A549 cells compared to other studied cancer cells. IC50 values for Salvurmin A and B against A549 cells were 35.6 ± 1.5 and 19.2 ± 0.8 µM, respectively. Based on annexin V staining, both of these compounds significantly induced apoptosis in A549 cells. Moreover, these two compounds significantly increased cell accumulation in G2/M and decreased the number of cells in G0/G1 phases in A549 cells in a dose-dependent manner. Conclusion: Based on the results Salvurmin B can be considered as potential candidate for further studies against human lung carcinoma

ACE genetic variability and response to fluoxetine: lack of association in depressed patients

Evidences suggest that besides the neurotransmitters contributing to the development of depression, renin-angiotensin system (RAS) may also have a substantial role. Certain polymorphisms of RAS are associated with over activity of RAS &amp; depression. Considering that antidepressants reduce the actions of angiotensin II, the main product of RAS, this may come into mind that genetic polymorphisms of the mentioned system may affect the outcome of therapy in depressed patients.In the present study, 100 newly diagnosed depressed patients, according to DSM-IV criteria, were treated with 20 mg of fluoxetine for 8-12 weeks. Patients were categorized into responsive and non-responsive groups according to 50% reduction in symptoms. Genotype frequencies of angiotensin-converting enzyme (ACE) gene [ACE (I/D, A-240T and A2350G)] were then determined in DNAs extracted from venous blood of the patients using polymerase chain reaction–restriction fragment length polymorphism (PCR– RFLP) and PCR.Results indicate that polymorphisms studied and their haplotypes were not associated with better response to fluoxetine. However, a strong association between age and treatment in depressed Iranian patients was observed (P=0.001).In conclusion, unlike previous reports, this study does not support the hypothesis of special genotypes of RAS contributing to a better response to antidepressants in depressed patients.</p

Stromal cell derived factor-1 genetic variation at locus 801 in patients with myasthenia gravis

ABSTRACT Background: Myasthenia gravis (MG) is the most common disorder of neuromuscular junction in which autoantibodies develop against nicotinic acetylcholine receptor for unknown reasons. The association of immunomodulator genes with different autoimmune disease has been studied in recent years. Objective: The aim of this study was to investigate correlation between a genetic variation in Stromal Cell Derived Factor-1 (SDF1) and susceptibility to MG in an Iranian population. Methods: Genotyping of SDF1 at position 801 G/A was performed by Polymerase Chain Reaction-Restriction Length Polymorphism (PCR-RFLP) in 87 patients with confirmed myasthenia gravis and 261 normal control subjects. Results: No statistically significant differences were observed in the frequencies of genotypes and alleles between patients and controls (p&gt;0.05). Furthermore, no significant differences in the genotype distribution were found between the cases with different stages (p&gt;0.05). Conclusion: Our data suggest that the SDF1 gene polymorphism at position 801 G/A is not associated with myasthenia gravis

Investigation of FOXP3 genetic variations at positions -2383 C/T and IVS9+459 T/C in southern Iranian patients with lung carcinoma

Objective(s): FOXP3 gene is an X-linked gene that encodes FOXP3 protein, an essential transcription factor in CD4+CD25+FOXP3+ regulatory T (Treg) cells.  We aimed, in the present study, to investigate the association of two FOXP3 polymorphisms, -2383 C/T (rs3761549) and IVS9+459 T/C (rs2280883), with lung cancer. Materials and Methods:  In a case-control study we analyzed genotypes and alleles frequencies at -2383 C/T and IVS9+459 T/C positions in 156 patients with lung cancer and 156 age and sex matched healthy controls in Southern Iranian population, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. The data were verified by direct automated DNA sequencing. Results: The frequency of -2383 T allele was significantly higher in the patients than in the control group (11.8% versus 5.9%, P-value=0.04, OR=2.13, 95%CI=1.04-4.54). T allele frequency at IVS9+459 T/C position was higher, compared to the controls, in the patients who presented the disease over 55 years old (69.9% versus 59.1%, P-value=0.04, OR=1.61, 95%CI=1.01-2.55) and also in SCLC patients (77.8% versus 59.1%, P-value=0.03, OR=2.42, 95%CI=1.05-5.59). No significant differences were found in the genotypes and haplotypes distributions between the cases and controls. A high degree of linkage disequilibrium was observed between two polymorphisms.  Conclusion: As the first study dealing with -2383 C/T and IVS9+459 T/C in lung cancer, our data conclusively suggest the association of -2383 T allele with susceptibility to lung cancer in Iranian population. The association of IVS9+459 T allele with susceptibility to lung cancer in old patients suggests the age-dependent effects of FOXP3 gene on cancer occurrence

Genetic Polymorphisms of CCL22 and CCR4 in Patients with Lung Cancer

Background: An association between lung cancer and chemokines has been advocated in the recent years. This study aims at investigating the association between lung cancer and 16C/A single nucleotide polymorphism (SNP) (rs. 4359426) in C-C motif chemokine 22 (CCL22) as well as C1014T SNP (rs. 2228428) in C-C chemokine receptor type 4 (CCR4), which serves as the receptor for CCL22. Methods: Genotyping was performed in 148 lung cancer patients and 148 normal controls using Polymerase Chain Reaction-Restriction-Fragment Length Polymorphism (PCR-RFLP). The data were verified by direct automated sequencing. Results: Frequencies of CC, CA and AA genotypes of 16C/A SNP in CCL22 gene were 112 (75.7%), 33 (22.3%) and 3 (2.0%) in patients, and 119 (80.4%), 24 (16.2%) and 5 (3.4%) in controls respectively. No significant differences were observed in genotype frequencies at this position between cases and controls (P=0.34). Moreover, there was no significant association between CCL22 polymorphism and types of lung cancer in patients. The distribution of CC, CT and TT genotypes of C1014T SNP in CCR4 gene, was 76 (51.4%), 60 (40.5%) and 12 (8.1%) in patients, and 80 (54.1%), 49 (33.1%) and 19 (12.8%) in controls respectively. No statistically significant differences were observed in genotypes frequencies of CCR4 gene between patients and controls (P=0.24). The genotype inherited by patients observed not to be associated with the type of lung cancer (P>0.05). Conclusion: Results reveal that CCL22 gene polymorphism at position 16C/A and CCR4 gene polymorphism at position C1014T, appear not to be associated with susceptibility to lung cancer

Investigation of Programmed Cell Death-1 (PD-1) Gene Variations at Positions PD1.3 and PD1.5 in Iranian Patients with Non-small Cell Lung Cancer

Background: Tumor cells express PD-1 ligands to bind PD-1 on immune cells and escape immune responses. In the present study, we aimed to investigate whether single nucleotide polymorphisms at positions PD1.3 (+7146, rs11568821) G/A, and PD1.5 (+7785 C/T, rs2227981) may be considered risk factors for susceptibility to nonsmall cell lung cancer in the Iranian population. Methods: This study enrolled 206 histopathologically confirmed lung cancer patients and 173 age/sex matched healthy controls. We performed PCR-RFLP to determine the genotypes of the extracted genomic DNA. Results: The frequencies of PD1.3 GG, GA and AA genotypes were 171 (83%), 31 (15%) and 4 (1.9%) out of 206 patients, and 144 (83.2%), 26 (15%), and 3 (1.7%) out of 173 controls, respectively. The frequencies of PD1.5 CC, CT and TT genotypes were 78 (37.9%), 100 (48.5%), and 28 (13.6%) in patients, and 60 (34.7%), 89 (51.4%), and 24 (13.9%) in controls. There were no significant differences in genotype analysis between patients and controls at positions PD1.3 (P=0.98) or PD1.5 (P=0.80). No significant differences existed in the frequencies of alleles and haplotypes between the two groups (P>0.05). Conclusion: Our data have indicated no association between PD1.3 (+7146) G/A and PD1.5 (+7785) C/T with susceptibility to non-small cell lung cancer. Investigation of other PD1 genetic variations and emerged haplotypes are required to completely define the role of PD1 genetic variations in susceptibility to lung cancer