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At least 505 records · Page 28Linked to original sources
PubMed1997

Oligonucleotides as modulators of cancer gene expression.

The delineation of gene function has always been an intensive subject of investigations. Recent advances in the synthesis and chemistry of oligonucleotides have now made these molecules important tools to study and identify gene function and regulation. Modulation of gene expression using oligonucleotides has been targeted at different levels of the cellular machinery. Triplex forming oligonucleotides, as well as peptide nucleic acids, have been used to inhibit gene expression at the level of transcription; after binding of these specific oligonucleotides, conformational change of the DNA's helical structure prevents any further DNA/protein interactions necessary for efficient transcription. Gene regulation can also be achieved by targeting the translation of mRNAs. Antisense oligonucleotides have been used to down-regulate mRNA expression by annealing to specific and determined region of an mRNA, thus inhibiting its translation by the cellular machinery. The exact mechanism of this type of inhibition is still under intense investigation and is thought to be related to the activation of RNase H, a ribonuclease that is widely available that can cleave the RNA/DNA duplex, thus making it inactive. Another well-characterized means of interfering with the translation of mRNAs is the use of ribozymes. Ribozymes are small catalytic RNAs that possess both site specificity and cleavage capability for an mRNA substrate, inhibiting any further protein formation. This review describes how these different oligonucleotides can be used to define gene function and discusses in detail their chemical structure, mechanism of action, advantages and disadvantages, and their applications.

Animals↗
PubMed2002

Importance, mechanisms and limitations of the distant bystander effect in cancer gene therapy of experimental liver tumors.

GCV-ablation of transplanted TK-positive liver tumors or the application of syngenic and allogenic HSV-TK/GCV oncolysates significantly reduced the size of synchronously growing untreated sister tumors in the liver. These TK-negative liver tumors constantly showed an increased infiltration by mononuclears (x4). The relative abundance of CD 4/8, NK and monocyte subtypes remained constant. The distant bystander effect was associated with a strong induction of GMCSF and IL-12 expression in the untreated TK-negative liver tumors. Analysis of the vbeta T-cell receptor profiles from TK-negative tumors did not point to clonal lymphocyte expansions. These results support the view of the 'distant bystander effect' as a predominantly local phenomenon, which is mediated by resident immune effectors rather than by MHC I restricted CD 3 positive lymphocytes.

Adenoviridae↗
PubMed1992

Learning about cancer genes through invertebrate genetics.

Genetic studies in yeast, nematodes and Drosophila are revealing the signal transduction pathways that regulate differentiation and cell proliferation. Some of the critical molecules involved are homologous to proto-oncogenes and others are likely to be analogous to the products of tumor suppressor genes.

Animals↗