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  Inhibition of induced chemoresistance by cotreatment with (E)-5-(2-bromovinyl)-2'-deoxyuridine (RP101)

Fahrig, R., Heinrich, J. C., Nickel, B., Wilfert, F., Leisser, C., Krupitza, G., et al. (2003). Inhibition of induced chemoresistance by cotreatment with (E)-5-(2-bromovinyl)-2'-deoxyuridine (RP101). Cancer Research, 63(18), 5745-5753.

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Genre: Journal Article
Alternative Title : Cancer Res.

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 Creators:
Fahrig, Rudolf, Author
Heinrich, Jörg Christian, Author
Nickel, Bernd, Author
Wilfert, Falk, Author
Leisser, Christina, Author
Krupitza, Georg, Author
Praha, Christian, Author
Sonntag, Denise, Author
Fiedler, Beate, Author
Scherthan, Harry1, Author           
Ernst, Heinrich, Author
Affiliations:
1Dept. of Human Molecular Genetics (Head: Hans-Hilger Ropers), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433549              

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 Abstract: Induced chemoresistance leads to the reduction of apoptotic responses. Although several drugs are in development that circumvent or decrease existing chemoresistance, none has the potential to prevent or reduce its induction. Here, we present data from a drug that could perhaps fill this gap. Cotreatment of chemotherapy with (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU, RP101) prevented the decrease of apoptotic effects during the course of chemotherapy and reduced nonspecific toxicity. Amplification of chemoresistance genes (Mdr1 and Dhfr) and overexpression of gene products involved in proliferation (DDX1) or DNA repair (UBE2N and APEX) were inhibited, whereas activity of NAD(P)H: quinone oxidoreductase 1 (NQO1) was enhanced. During recovery, when treatment was with BVDU only, microfilamental proteins were up-regulated, and proteins involved in ATP generation or cell survival (STAT3 and JUN-D) were down-regulated. That way, in three different rat tumor models, the antitumor efficiency of chemotherapy was optimized, and toxic side effects were reduced. Because of these beneficial properties of BVDU, a clinical pilot Phase I/II study with five human tumor entities has been started at the University of Dresden (Dresden, Germany). So far, no unwanted side effects have been observed.

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Language(s): eng - English
 Dates: 2003-09-15
 Publication Status: Issued
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: eDoc: 126752
ISI: 000185672600017
 Degree: -

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Title: Cancer Research
  Alternative Title : Cancer Res.
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 63 (18) Sequence Number: - Start / End Page: 5745 - 5753 Identifier: ISSN: 0008-5472