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Transcriptional silencing induced by hypermethylation of CpG islands in the promoter regions of genes is believed to be an important mechanism of carcinogenesis in human cancers including epithelial ovarian cancer (EOC). Previously published data on gene methylation of EOC focused mainly on single gene or on cancer tissues. Objectives of the study were to estimate the promoter hypermethylation status of DAPK1 and p16INK4a genes in circulating blood of EOC patients and to determine their association with clinicopathological features of EOC. This case–control study included 50 EOC patients and 20 apparently healthy and age matched female controls. Isolation of genomic DNA was carried out from peripheral venous blood. Methylation in promoter region of DAPK1 and p16INK4a genes was determined by methylation-specific PCR. Methylation of DAPK1 was occurred in 42 out of 50 cases (84.0%) and methylation of p16INK4a gene was occurred in 34 out of 50 cases (68.0%). Methylation of both genes was occurred in 25 cases (50.0%). Occurrence of methylation in DAPK1 and p16INK4a genes was statistically significant (p

The influence of Estrogen Receptor 1 (ESR1) gene -397T>C (PvuII) and -351A>G (XbaI) polymorphisms on the risk of development of coronary artery disease (CAD) in the north Indian population was analysed. We hypothesized that ESR1 gene polymorphisms may influence the susceptibility to CAD through variation in Estrogen Receptor α (ERα) expression. To assess this concept, we evaluated ERα mRNA expression in blood plasma of CAD patients. The study included hundred CAD patients who showed presence of greater than 50% luminal stenosis in at least one major coronary artery in angiography along with hundred age and sex matched healthy controls. The ESR1 polymorphisms were investigated by PCR–RFLP. Quantitative Real Time PCR was carried out for the measurement of ERα mRNA expression. The results showed that genotypic frequencies of ESR1 -397T>C and -351A>G gene polymorphisms were significantly higher in CAD patients than control subjects (p C polymorphism, the ERα mRNA expression was highest in CAD patients with wild type homozygous TT genotype (2−∆ct = 0.28). A mutant ‘C’ allele, dose dependent, significant decrease in trend in ERα mRNA expression was observed, with lowest expression in mutant homozygous CC genotype (2−∆ct = 0.09), and intermediate expression level in heterozygous TC genotype (2−∆ct = 0.14) subgroups of CAD patients. In conclusion, this study demonstrates a significantly heightened risk of CAD associated with the inheritance of mutant genotypes of ESR1 -397T>C and -351A>G gene polymorphisms, in the north Indian population. This is the first report of a lowered ERα mRNA expression in conjunction with the presence of mutant ‘C’ allele of ESR1 -397T>C polymorphism with consequent increased CAD susceptibility.

Background:Epithelial ovarian cancer continues to be a deleterious threat to women as it is asymptomatic and is typically detected in advanced stages. Cogent non-invasive biomarkers are therefore needed which are effective in apprehending the disease in early stages. Recently, miRNA deregulation has shown a promising magnitude in ovarian cancer tumorigenesis. miRNA-145(miR- 145) is beginning to be understood for its possible role in cancer development and progression. In this study, we identified the clinicopathological hallmarks altered owing to the downexpression of serum miR-145 in EOC.Methods:70 serum samples from histopathologically confirmed EOC patients and 70 controls were collected. Total RNA from serum was isolated by Trizol method, polyadenylated and reverse transcribed into cDNA. Expression level of miR-145 was detected by miRNA qRT-PCR using RNU6B snRNA as reference.Results:The alliance of miR-145 profiling amongst patients and controls established itself to be conspicuous with a significant p-value (pConclusion:Our results propose that miR-145 down-regulation might be a possible touchstone for disease progression and be identified as a diagnostic marker and predict disease outcome in EOC patients.

Cancer is one of the major global health problems, responsible for the second-highest number of deaths. The genetic and epigenetic changes in the oncogenes or tumor suppressor genes alter the regulatory pathways leading to its onset and progression. Conventional methods are used in appropriate combinations for the treatment. Surgery effectively treats localized tumors; however, it fails to treat metastatic tumors, leading to a spread in other organs, causing a high recurrence rate and death. Among the different strategies, the nanocarriers-based approach is highly sought for, but its nonspecific delivery can cause a profound side effect on healthy cells. Targeted nanomedicine has the advantage of targeting cancer cells specifically by interacting with the receptors overexpressed on their surface, overcoming its non-specificity to target healthy cells. Nanocarriers prepared from biodegradable and biocompatible materials are decorated with different ligands by encapsulating therapeutic or diagnostic agents or both to target cancer cells overexpressing the receptors. Scientists are now utilizing a theranostic approach to simultaneously evaluate nanocarrier bio-distribution and its effect on the treatment regime. Herein, we have summarized the recent 5-year efforts in the development of the ligands decorated biodegradable nanocarriers, as a targeted nanomedicine approach, which has been highly promising in the treatment of cancer.

Escalated PD-L1 expression has been identified during malignant transformation in a number of cancer types and helps cancer cells escape an effective anti-tumor immune response. The mechanisms underlying escalated production of PD-L1 in many cancers, however, are still far from clear. We studied PD-L1, STAT3 and STAT5 mRNA expression using qRT-PCR in 72 BCR/ABL1 negative myeloproliferative neoplasm (MPN) patients (39 polycythemia vera and 33 essential thrombocythemia). Furthermore, phosphorylation status of STAT3 and STAT5 was studied using immunoblotting in the same patients. All MPN patients were first screened for JAK2 (V617F) mutation by tetra-primer ARMS-PCR, followed by quantification of JAK2 (V617F) mutation burden in all V617F positive MPN patients by ASO-PCR. Patients were screened for BCR/ABL1 fusion gene transcripts to rule out Ph positive status. Our findings showed that mRNA levels of PD-L1 and STAT3 were significantly higher in JAK2 (V617F) MPN patients, while as STAT5 was insignificantly upregulated. STAT3 and STAT5 phosphorylation was seen to be higher in JAK2 (V617F) MPN patients compared to the JAK2 (WT) patients. Upregulation of PD-L1, STAT3 and STAT5 was significantly associated with JAK2 (V617F) percentage in MPN patients. PD-L1, STAT3 and STAT5 expression significantly and positively correlated with JAK2 (V617F) allele burden. In addition, significant coexpression of PD-L1 with STAT3 and STAT5 was observed in MPN patients. In summary, JAK2 (V617F) mutation is accompanied by increased PD-L1 expression and this PD-L1 over expression is mediated by JAK2 (V617F) mainly through STAT3, while as STAT5 may play a minor role.

The asymptomatic behaviour of esophageal cancerous cells at early stages develops advanced clinical presentation of the disease, resulting in poor prognosis and curbed intervention of therapeutic modalities. The endeavours to detect diagnostic and prognostic markers have been proven futile at the clinical platform. While several biomarkers have been investigated, including CYFRA 21-1, carcinoembryonic antigen and squamous cell carcinoma antigen, their sensitivity has not proved consistently satisfactory across the various stages of esophageal cancer. Hence, there is an impending requirement of biomarkers for early diagnosis and better prognosis. In the recent past, next generation sequencing (NGS) tool has emerged as an important tool to highlight the hallmarks of esophageal cancer (EC). This review summarizes the changes/mutations occurred in tumor cells during carcinogenesis and addresses the contribution of NGS techniques, viz. whole genome sequencing (WGS), RNA-Sequencing and Exome sequencing (ES), in EC. Additionally, this review highlights the connection between the findings from these techniques. An effort has been made to emphasize the genes affected and involved signaling pathway in EC. Further, investigations of these mutated genes would not only shed light on the relevant genes to be studied but also help in the better management and cure through personalized therapy.

Despite extensive clinical research and management protocols applied in the field of coronary artery diseases (CAD), it still holds the number 1 position in mortality worldwide. This indicates that we need to work on precision medicine to discover the diagnostic, therapeutic, and prognostic targets to improve the outcome of CAD. In precision medicine, epigenetic changes play a vital role in disease onset and progression. Epigenetics is the study of heritable changes that do not affect the alterations of DNA sequence in the genome. It comprises various covalent modifications that occur in DNA or histone proteins affecting the spatial arrangement of the DNA and histones. These multiple modifications include DNA/histone methylation, acetylation, phosphorylation, and SUMOylation. Besides these covalent modifications, non-coding RNAs—viz. miRNA, lncRNA, and circRNA are also involved in epigenetics. Smoking, alcohol, diet, environmental pollutants, obesity, and lifestyle are some of the prime factors affecting epigenetic alterations. Novel molecular techniques such as next-generation sequencing, chromatin immunoprecipitation, and mass spectrometry have been developed to identify important cross points in the epigenetic web in relation to various diseases. The studies regarding exploration of epigenetics, have led researchers to identify multiple diagnostic markers and therapeutic targets that are being used in different disease diagnosis and management. Here in this review, we will discuss various ground-breaking contributions of past and recent studies in the epigenetic field in concert with coronary artery diseases. Future prospects of epigenetics and its implication in CAD personalized medicine will also be discussed in brief.

GABA has always been an inviting target in the etiology and treatment of epilepsy. The GABRA1, GABRG2, and GABRD genes provide instructions for making α1, ϒ2, and δ subunits of GABAA receptor protein respectively. GABAA is considered as one of the most important proteins and has found to play an important role in many neurological disorders. We explored the association of GABAA receptor gene mutation/SNPs in JME and LGS patients in Indian population. A total of 100 epilepsy syndrome patients (50 JME and 50 LGS) and 100 healthy control subjects were recruited and analyzed by AS-PCR and RFLP-PCR techniques. In our study, GABRA1 965 C > A mutation and 15 A > G polymorphism gene may play an important role in modulating the drug efficacy in LGS patients. The GABRA1 15 A > G polymorphism may also play an important role in the susceptibility of LGS and the inheritance of GG genotype of this polymorphism may provide an increased risk of development of LGS. The GABRG2 588 C > T polymorphism may decrease the duration of seizures in JME patients. The GABRD 659 G > A polymorphism may play an important role in the susceptibility of JME and LGS and this polymorphism may also increase the duration of postictal period in JME patients but may decrease the duration of seizure in LGS patients.

Introduction: Epilepsy is the most common heterogeneous neurological disorder affecting approximately 42 million people worldwide. Juvenile myoclonic epilepsy (JME) is a common form of idiopathic generalized epilepsy representing 5-10% of all epilepsy cases. Lennox-Gastaut syndrome (LGS) is one of the most severe epileptic encephalopathies of childhood onset, the cause of which may be symptomatic, i.e., secondary to an underlying brain disorder or cryptogenic, i.e., with no known cause. Sodium channels are integral membrane proteins which play a central role in neuronal membrane excitability and action potential generation. Alpha subunit of voltage gated sodium channels encoded by SCN1A, SCN2A and other genes is pivotal for neuronal signalling. It was planned to analyse the roles of SCN1A Thr1067Ala and SCN2A Arg19Lys polymorphisms in the pathophysiology and risk JME and LGS in the Indian population. Methods: A total of 50 JME patients, 50 LGS Patients and 100 age and sex matched healthy volunteers were recruited in this study. The genotyping of SCN1A Thr1067Ala i.e., 3184 A>G (rs2298771) and SCN2A Arg19Lys i.e., 56 G>A (rs17183814) polymorphism was performed by polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) analysis. Results: The SCN1A Thr1067Ala polymorphism genotypic distribution in LGS was significantly different from the normal population (P=0.008), with mutant homozygous (GG) plus heterozygous (AG) genotypes’ percentage in LGS patients (16%) being lower than in healthy controls (24%). Frequency of the mutant ‘G’ allele of this SNP in LGS patients was 0.1, while it was 0.2 in control subjects (P=0.04). These observations which suggest a protective role of SCN1A Thr1067Ala polymorphism in LGS, were in sync with computation of an odds ratio of 0.21 (95% CI 0.07 to 0.66, p=0.005) for the GG genotype in LGS patients. Though no correlation of SCN1A Thr1067Ala SNP with the severity of disease phenotype in LGS viz. frequency/duration of seizures etc. was noted, a conflicting finding was the significant association of its mutant genotypes with an early age of onset of the syndrome (p=0.007). Contrary to the findings in SCN1A Thr1067Ala, in case of SCN2A Arg19Lys polymorphism, though a significantly different genotypic distribution was present in LGS, in comparison to normal population (p=0.03), the mutant homozygous (AA) and heterozygous (GA) combined percentage in LGS patients (16%) was greater than in healthy controls (11%). This was complemented by observation of an odds ratio of 4.24 (95% CI 1.15 to 15.55, p=0.029, in case of LGS patients with heterozygous (GA) genotype, indicative of an increased disease susceptibility. Unlike LGS, in JME patients no significant differences in genotypic/allelic frequencies of SCN1A Thr1067Ala and SCN2A Arg19Lys polymorphisms were noted and the associated odds ratios for mutant genotypes were also non-significant. Conclusion: The SCN1A Thr1067Ala and SCN2A Arg19Lys polymorphisms may play contrary roles in the pathophysiology of LGS. Inheritance of SCN1A Thr1067Ala mutant allele decreases the susceptibility for LGS occurrence, and may hamper Na+ channels opening and neuronal excitability. On the other hand, the mutant allele of SCN2A Arg19Lys polymorphism confers an increased risk for development of LGS, consequent to a likely facilitatory effect on action potential generation and misfiring in neurons. Neither of these two SNPs appears to influence the pathogenesis/susceptibility to JME.

Platelet-derived growth factor receptor has been implicated in many malignant and non-malignant diseases. Platelet-derived growth factor receptor-α is a tyrosine kinase and a side target for imatinib, a revolutionary drug for the treatment of chronic myeloid leukemia that has dramatically improved the survival of chronic myeloid leukemia patients. Given the importance of platelet-derived growth factor receptor in platelet development and its inhibition by imatinib, it was intriguing to analyze the role of platelet-derived growth factor receptor-α in relation to imatinib treatment in the development of imatinib-induced thrombocytopenia in chronic myeloid leukemia patients. We hypothesized that two known functional polymorphisms, +68GA insertion/deletion and −909C/A, in the promoter region of the platelet-derived growth factor receptor-α gene may affect the susceptibility of chronic myeloid leukemia patients receiving imatinib treatment to the development of thrombocytopenia. A case-control study was conducted among a cohort of chronic myeloid leukemia patients admitted to the Lok Nayak Hospital, New Delhi, India. A set of 100 patients of chronic myeloid leukemia in chronic phase and 100 age- and sex-matched healthy controls were studied. After initiation of imatinib treatment, the hematological response of chronic myeloid leukemia patients was monitored regularly for 2 years, in which the development of thrombocytopenia was the primary end point. Platelet-derived growth factor receptor-α promoter polymorphisms +68GA ins/del and −909C/A were studied by allele-specific polymerase chain reaction. Platelet-derived growth factor receptor-α messenger RNA expression was evaluated by quantitative real-time polymerase chain reaction. The messenger RNA expression results were expressed as 2 −Δct ± standard deviation. The distribution of +68GA ins/del promoter polymorphism genotypes differed significantly between the thrombocytopenic and non-thrombocytopenic chronic myeloid leukemia patient groups (p