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1.
Pakistan Journal of Pharmaceutical Sciences. 2015; 28 (3)
in English | IMEMR | ID: emr-191729

ABSTRACT

Epigenetics means the study of alterations in the genetic material that affect the phenotype but does not affect the genotype. Epigenetics cause alterations in cell properties, which are inherited; but it does not cause alterations in DNA sequence. Epigenetic mediated silencing of gene is of four types, which are DNA methylation, histone deacetylation, RNA associated silencing and Genomic imprinting. Other factors [environmental and xenobiotics] can also cause gene silencing but DNA methytlation and changes in histones of chromatin are two important changes, which are responsible for malignant diseases. Two groups of drugs are under development, which corrects the epigenetic alterations. These are histone deacetylation [HDAC] inhibitors and DNA methytransferase [DNMT] inhibitors. These drugs may be used in cancer because in cancer, hypermethylation of cancer suppressor gene causes gene silencing. Epigenetic therapy scope is likely to increase in future.

2.
Pakistan Journal of Pharmaceutical Sciences. 2014; 27 (5): 1371-1377
in English | IMEMR | ID: emr-195096

ABSTRACT

Prostate cancer is a multifaceted disease that arises because of misrepresentation of linear and integrated signaling cascades that regulate gene network in normal and cancer cells


Programmed cell death is modulated by intracellular regulators within each cell and various lines of evidence suggest that there is under- expression and over-expression of pro-apoptotic and anti-apoptotic gene subsets respectively


Apoptosis is a response to the cellular microenvironment, and the cell microenvironment can be regulated by multiple signaling cascades at a higher organizational level by suppressing survival signals notably at genetic, epigenetic, transcriptional and post-transcriptional level


Unquestionably, drug-discovery approaches over the last decade aiming at neutralizing anti-apoptotic proteins, over-expressing pro-apoptotic proteins and enhancing the cell surface appearance of TRAIL receptors have revolutionized our current information about inducing and maximizing TRAIL mediated signaling in resistant prostate cancer phenotype. In this mini-review we outline outstanding developments in the field of prostate cancer that have played a role in understanding the underlying mechanisms that control TRAIL mediated apoptosis in prostate cancer cells, which may be helpful in the development of cancer therapies based on the apoptotic pathway

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