Natural Killer Cells Expanded and Preactivated Exhibit Enhanced Antitumor Activity against Different Tumor Cells in Vitro.

One of the emerging treatment strategies for cancer particularly for haematological malignancies is natural killer (NK) cell therapy. However, the availability of a best approach to maximize NK cell anticancer potential is still awaited. It is well established that cytokine-induced memory-like NK cells have the potential to differentiate after a short period of preactivation with interleukins-IL-12, IL-15, and IL-18 and exhibit increased responses to cytokine or activating receptor restimulation for weeks to months after preactivation. We demonstrated that NK cells differentiated from CD34+ cells isolated from cord blood show increased antitumor potential in vitro against different cancer cells. Using flow cytometry, we found that NK cells were able to induce apoptosis in cancer cells in vitro. We further analysed surviving gene expression by quantitative real time PCR and reported that NK cells cause down regulation of survivin gene expression in tumor cells. Therefore, NK cell therapy represents a promising immunotherapy for cancers like AML and other haematological malignancies. It concluded that NK cells can be differentiated from CD34+ cells isolated from cord blood ,are able to induce apoptosis and induce increased antitumor potential in vitro against different cancer cells besides cause downregulation of survivin gene expression in tumor cells. Therefore, NK cell therapy represents a promising immunotherapy for different cancer types and haematological malignancies. Furthers studies are necessary to confirm our findings.
.

Evaluating NISCH and CDH1 Promoter Hypermethylation in Nonsmokers, Cancer Free Smokers and Lung Cancer Patients: A Case Control Study.

Lung cancer has very high mortality due to late stage diagnosis not amenable to curative resection. Cancer specific methylation patterns of tumor suppressor genes may precede precursor lesions of lung cancer. Our aim was to evaluate the promoter hypermethylation of tumor suppressor gene NISCH and CDH1 in cfDNA from plasma of lung cancer patients and its possible correlation with smoking status and various clinicopathological parameters. Forty histopathologically confirmed lung cancer cases, thirty smoker and thirty nonsmoker controls were enrolled. Plasma cfDNA was extracted and subjected to bisulfite treatment followed by MS-PCR. Serum nischarin levels were estimated by ELISA. The frequency of promoter hypermethylation of NISCH and CDH1 was significantly higher in lung cancer patients as compared to lifelong non-smoker controls (p < 0.05). It did not vary with smoking status among cancer cases. No significant association was found with staging or histological grading. NISCH methylation was found to be significantly higher among smoker controls. Pack years and packs per day were significantly higher in the methylated group. Serum nischarin levels showed no significant association with NISCH methylation or clinicopathological variables. NISCH is highly methylated in both high risk smoker controls as well as cancerousnon-smokers and may mark the convergence of varied etiologies of lung cancer. Hence NISCH and CDH1 are highly methylated in plasma cfDNA of lung cancer patients.

OLR1 Gene Polymorphism and Oxidized LDL Levels in Metabolic Syndrome in Indian Population.

OBJECTIVE: Metabolic syndrome (MetS) is associated with abnormal lipid profile and high cardiovascular risk. There is an increased prevalence of coronary artery disease and Type 2 Diabetes Mellitus in India. Oxidized Low Density Lipoprotein Receptor 1(OLR1), a cell surface endocytosis receptor recognize, internalize and degrade oxidized LDL (oxLDL) in vascular endothelium and plays a role in the pathogenesis of atherosclerosis. The aim was to explore the association of OLR1 gene polymorphism and measure the serum levels of ox-LDL in patients with MetS in Indian population. MATERIALS AND METHODS: Forty cases fulfilling the IDF diagnostic criteria for MetS and 40 healthy controls having similar age and sex ratio were genotyped for OLR1 gene (SNP: IVS4-73C>T , rs3736234) by RFLP-PCR. Serum ox-LDL was estimated by ELISA.Their BP, BMI and waist circumference were measured. Fasting Plasma glucose, Serum Triglyceride and HDL-C were measured. RESULTS: Serum oxLDL was significantly higher in MetS cases as compared to controls (p < 0.0001). Odds ratio of T allele of above OLR1 SNP among subjects with MetS was 14.79 (95%CI: 1.80-121.2, p < 0.05). But no association was found between the SNP and serum ox-LDL levels. People having TT allele had higher BMI compared to those having CC allele. CONCLUSION: Ox LDL, being more atherogenic might contribute in the pathogenesis of MetS. The intronic SNP: IVS4-73 C>T of OLR1 gene increases the risk of developing MetS by a yet unknown mechanism that is independent of rise in ox-LDL. This OLR1 SNP probably influences BMI.

Effect of CYP1A1 gene polymorphism and psychological distress on seminal analysis parameters.

BACKGROUND: Psychological factor alters fertility hormones and contributes to male infertility. Anxiety and depression are common manifestations of psychological distress. Cytochrome P-4501A1 (CYP1A1) metabolizes xenobiotics and fertility hormones that influence male fertility. The effect of CYP1A1 polymorphism on male fertility has remained controversial. The present study was designed to assess the effect of psychological distress and CYP1A1 polymorphisms and their interactions on parameters of seminal analysis. METHODS: Eighty male partners of infertile couples were evaluated for level of distress using Hospital anxiety and depression score (HADS) questionnaire. As per WHO guidelines (2010), sperm count, motility and morphology were assessed and subjects were classified as (a) subjects having normal sperm characteristics and (b) subjects having abnormal sperm characteristics. CYP1A1 polymorphisms were detected by ASO-PCR. RESULTS: The significant odd's ratio indicates that psychological distress (OR:10.54; CI:3.72-29.84; P < 0.001), CYP1A1*4(OR:10.31; CI:3.01-35.24; P < 0.001) and CYP1A1*2C (OR:7.01; CI:1.78-27.56; P = 0.002) polymorphisms are risk factors for the development of abnormal sperm characteristics in male subjects. Data analysis with two way ANOVA shows that psychological distress, CYP1A1*4 and CYP1A1*2C polymorphisms significantly affect but do not interact among them to influence sperm parameters. CONCLUSIONS: It is concluded that CYP1A1 gene polymorphisms and psychological distress act independently but do not interact with each other in pathogenesis of male infertility.