Variants of bcl-2 specific siRNA for silencing antiapoptotic bcl-2 in pancreatic cancer

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PANCREATIC CANCER Variants of bcl-2 specific siRNA for silencing antiapoptotic bcl-2 in pancreatic cancer

Background and aims: Pancreatic cancer remains a devastating diagnosis with only limited therapeutic options. Specific inhibition of expression of target genes has become possible using small interfering (si) RNAs. We therefore investigated how far siRNA specific for bcl-2 may serve as a therapeutic option for pancreatic cancer in vitro and in vivo. Methods: siRNAs targeting two different regio...

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Variants of bcl-2 specific siRNA for silencing antiapoptotic bcl-2 in pancreatic cancer.

BACKGROUND AND AIMS Pancreatic cancer remains a devastating diagnosis with only limited therapeutic options. Specific inhibition of expression of target genes has become possible using small interfering (si) RNAs. We therefore investigated how far siRNA specific for bcl-2 may serve as a therapeutic option for pancreatic cancer in vitro and in vivo. METHODS siRNAs targeting two different regio...

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Bcl-2 family genes play a central role in cell apoptosis and cell proliferation, and are implicated in the pathology of many malignancies. We explored different ways of introducing siRNA duplexes into cells, comparing "naked" with lipoplexand polyplex-based formulations in order to decrease the level of the Bcl-2 and Bcl-xL proteins. Our results show that siRNA binds efficiently to all cationic...

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Solution structure of the antiapoptotic protein bcl-2.

The structures of two isoforms of Bcl-2 that differ by two amino acids have been determined by NMR spectroscopy. Because wild-type Bcl-2 behaved poorly in solution, the structures were determined by using Bcl-2/Bcl-x(L) chimeras in which part of the putative unstructured loop of Bcl-2 was replaced with a shortened loop from Bcl-x(L). These chimeric proteins have a low pI compared with the wild-...

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Guided by a combination of nuclear magnetic resonance binding assays and computational docking studies, we synthesized a library of 5,5' substituted Apogossypol derivatives as potent Bcl-XL antagonists. Each compound was subsequently tested for its ability to inhibit Bcl-XL in an in vitro fluorescence polarization competition assay and exert single-agent proapoptotic activity in human cancer ce...

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ژورنال

عنوان ژورنال: Gut

سال: 2005

ISSN: 0017-5749

DOI: 10.1136/gut.2004.056192