Publications (3)14 Total impact
-
Article: Challenges in molecular analysis for individualized cancer therapy.
Drug Discovery Today 07/2003; 8(12):531. · 6.83 Impact Factor -
Article: Altered expression of mRNAs for apoptosis‐modulating proteins in a low level multidrug resistant variant of a human lung carcinoma cell line that also expresses mdr1 mRNA
[show abstract] [hide abstract]
ABSTRACT: An in vitro model that might be relevant to cancer cell chemoresistance in vivo was generated by exposing the human lung carcinoma clonal cell line DLKP-SQ to 10 sequential pulses of pharmacologically attainable doses of doxorubicin. The resistant variant, DLKP-SQ/10p, was found to be cross-resistant to doxorubicin (10×), vincristine (43×), etoposide (3×), sodium arsenate (3×), paclitaxel (38×) [which could imply overexpression of P-glycoprotein (P-gp) and possibly increased multidrug resistance-associated protein activity] and 5-fluorouracil (4×), but slightly sensitized to carboplatin. Analysis of mRNA levels in the resistant variant revealed overexpression of mdr1 mRNA without significant alteration in mrp, Topo. IIα, GSTπ, dhfr or thymidylate synthase mRNA levels. Overexpression of the anti-apoptotic bcl-xL transcript and the pro-apoptotic bax mRNA was also detected but no alterations in bcl-2 or bag-1 mRNA levels were observed. Resistance to a P-gp-associated drug, doxorubicin, could be reversed with P-gp circumventing agents such as cyclosporin A and verapamil, but these substances had no effect on resistance to 5-fluorouracil. Overexpression of the pro-apoptotic bcl-xS gene in the DLKP-SQ/10p line partially reversed resistance not only to P-gp-associated drugs but also to 5-fluorouracil, indicating that the ratio of bcl family members may be important in determining sensitivity to chemotherapeutic drug-induced apoptosis. Int. J. Cancer 82:368–376, 1999. © 1999 Wiley-Liss, Inc.International Journal of Cancer 07/1999; 82(3):368 - 376. · 5.44 Impact Factor -
Article: Construction and transfection of a ribozyme targeting human caspase-3.
[show abstract] [hide abstract]
ABSTRACT: Caspase-3 is a key executioner cysteine protease involved in programmed cell death or apoptosis. A ribozyme to human caspase-3 was designed, tested by in vitro cleavage, and transfected into a drug-resistant variant (DLKP-A5F) of a human lung carcinoma cell line (DLKP). By both stable and transient transfection, this ribozyme was shown to be effective at down-regulating human caspase-3 mRNA and protein levels.Anticancer research 24(2A):425-31. · 1.73 Impact Factor
Top Journals
Institutions
-
1999
-
Dublin City University
Dublin, L, Ireland (Republic of Ireland)
-