Rauf Ahmad Najar

Indian Institute of Integrative Medicine, Jammu City, Kashmir, India

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Publications (6)9.23 Total impact

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    ABSTRACT: Placental development is known for its resemblance with tumor development, such as in the expression of oncogenes (c-myc) and telomerase (hTERT). The expression of c-myc and hTERT is upregulated during early pregnancy and gestational trophoblastic diseases (GTDs). To determine the role of DNA methylation [via methylation specific-high resolution melting (MS-HRM)]and histone modifications [via chromatin immunoprecipitation (ChIP assay)] in regulating the differential expression of c-myc and hTERT during normal gestation and their dysregulation during placental disorders we obtained placental samples from 135 pregnant women, in five groups; normal first, second and third trimester (n=30 each), preeclamptic pregnancy (n=30) and molar pregnancy (n=15). Two placental cell lines (JEG-3 and HTR-8/SVneo) and isolated first trimester cytotrophoblasts were also studied. Quantitative RT-PCR revealed decreased mRNA expression levels of c-myc and hTERT, which were associated with a higher level of H3K9me3 (1.5 fold, p<0.05) and H3K27me3 (1.9 fold, p<0.05), respectively, in third trimester placental villi versus first trimester villi. A significantly lower level of H327me3 in molar placenta was associated with higher mRNA expression of c-myc and hTERT. Development of PE was associated with increased methylation (p<0.001) and H3K27me3 (p<0.01) at the c-myc promoter with reduced H3K9me3 (p<0.01) and H3K27me3 (p<0.05) at the hTERT promoter. Further, mRNA expression of c-myc and hTERT was strongly correlated in molar villi (r= 0.88, p<0.01) and JEG-3 cells (0.99, p<0.02). Moreover, on the basis of methylation data, we demonstrates the potential of c-myc as a fetal DNA epigenetic marker for preeclamptic pregnancies. Thus we suggest a role for epigenetic mechanisms in regulating differential expression of c-myc and hTERT during placental development and use of the c-myc promoter region as a potential fetal DNA marker in case of PE.
    Molecular Human Reproduction 07/2014; · 4.54 Impact Factor
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    ABSTRACT: Cancer is a diverse class of diseases which differ widely in their cause and biology. The aberrant behavior of cancer reflects up regulation of certain oncogenic signaling pathways that promote proliferation, inhibit apoptosis, and enable the cancer to spread and evoke angiogenesis. Phosphoinositide-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway controls various biological processes that are important for normal functioning of the cell via cell cycle progression, survival, migration, transcription, translation and metabolism. However, PI3K signaling pathway is dysregulated almost in all cancers and dysregulation of this signaling is due to the amplification and genetic mutation of PI3K gene, encoding catalytic and regulatory subunit of PI3K isoforms. The current review focuses on the structural features of various PI3K isoforms including Akt and mTOR and their inhibition using specific small molecule inhibitors in an attempt to achieve an attractive target for cancer prevention and chemotherapy.
    Anti-cancer agents in medicinal chemistry 02/2013;
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    ABSTRACT: Folate mediated one-carbon metabolism is of fundamental importance for various cellular processes, including DNA synthesis and methylation of biological molecules. Due to the exogenous requirement of folate in mammals, there exists a well developed epithelial folate transport system for regulation of normal folate homeostasis. The intestinal and renal folate uptake is tightly and diversely regulated and disturbances in folate homeostasis like in alcoholism have pathological consequences. The study was sought to delineate the regulatory mechanism of folate uptake in intestine and reabsorption in renal tubular cells that could evaluate insights of malabsorption during alcoholism. The folate transporters PCFT and RFC were found to be associated with lipid rafts of membrane surfaces in intestine and kidney. Importantly, the observed lower intestinal and renal folate uptake was associated with decreased levels of folate transporter viz. PCFT and RFC in lipid rafts of intestinal and renal membrane surfaces. The decreased association of folate transporters in lipid rafts was associated with decreased protein and mRNA levels. In addition, immunohistochemical studies showed that alcoholic conditions deranged that localization of PCFT and RFC. These findings could explain the possible mechanistic insights that may result in folate malabsorption during alcoholism.
    Alcohol (Fayetteville, N.Y.) 12/2012; · 2.41 Impact Factor
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    ABSTRACT: Cancer cells compared to their normal counterparts reveal different metabolic needs and this differential requirement of metabolic intermediates and their subsequent consequences require an elaborate understanding of cancer cell metabolism and increased energy production in these cells. Nevertheless these metabolic differences have provided opportunities for developing novel therapeutic approaches for the cancer diagnosis and treatment. In addition enhanced proliferative capacities of tumor cells associated with aberrations of many signal transduction pathways resulting from genetic or epigenetic alterations has made it possible to develop countless targeted therapeutics for several types of malignancies. However at present most of our understanding about the dysregulated cancer cell metabolism is at physiological stages. With advancement in technology development, we may eventually be able to differentiate the metabolic differences between normal cells and cancerous at the single-tumor level that may influence the development of personalized cancer medicine. In this review, the focal point will be the recent developments in understanding the crucial role of metabolic enzymes, oncogenes and tumor suppressor genes in progression of cancer and their targeting to establish the most appropriate therapeutic strategies for better clinical outcome.
    Journal of Cancer Science and Therapy 08/2012; 4(9):281-291.
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    ABSTRACT: Cancer is a pathologic condition that involves genetic and epigenetic events culminating in neoplastic transformation. Alteration in epigenetic events that regulate the transcriptional activity of genes associated with various signaling pathways can influence multiple stages of tumorigenesis. In cancer cells, an imbalance often exists between histone acetyl transferase and histone deacetylase (HDAC) activities, and current research focuses actively on seeking competitive HDAC inhibitors (HDACi) for chemotherapeutic intervention. HDACi are proving useful for cancer prevention and therapy by virtue of their ability to reactivate the expression of epigenetically silenced genes, including those involved in differentiation, cell cycle regulation, apoptosis, angiogenesis, invasion, and metastasis. Furthermore, epidemiological studies suggest that different diets such as intake of cruciferous vegetables may lower the risk of different cancers, and there is growing interest in identifying the specific chemoprotective constituents and mechanistic insights of their action. Interestingly, it has been observed that cancer cells are more sensitive than nontransformed cells to apoptotic induction by some HDACi. Although the mechanistic basis for this sensitivity is unclear, yet HDACi have emerged as important epigenetic target for single and combinatorial chemotherapy. HDACi derived from diverse sources such as microbial, dietary, and synthetic increase acetylation level of cells and bring about anti-proliferative and apoptotic effects specific to cancer cells by way of their role in cell cycle regulation and expression of epigenetically silenced genes.
    DNA and cell biology 03/2012; 31 Suppl 1:S62-71. · 2.28 Impact Factor
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    Article: Article
    Journal of Cancer Science and Therapy 01/2012;