Adriamycin (ADR) (NSC-123127) uptake and retention in ADR-sensitive P388 leukemia (P388/S) and ADR-resistant P388 leukemia (p388/R) cells were compared by fluorometry and laser flow cytometry (FCM) and were correlated with cytotoxic effects. Drug levels in P388/R cells treated in vitro with ADR (1-10 micrograms/ml) were twofold to fourfold lower than were levels in similarly treated P388/S cells FCM analysis of P388/S and P388/R cells exposed in vitro to ADR showed qualitative and quantitative differences in ADR fluorescence profiles of drug-treated cells (1-5 micrograms/ml) but not of the isolated nuclei (0.5- 10 micrograms/ml). Drug-induced perturbations in cell cycle traverse and chromosome aberrations were seen in P388/S but not in P388/R cells treated with 0.5-5 micrograms ADR/ml in vitro or 4-8 mg ADR/kg in vivo. The role of FCM in rapidly comparing and quantitating cellular ADR fluorescence profiles of ADR-sensitive and ADR-resistant tumors was demonstrated.
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Ann Pharm Fr
March 2006
Laboratoire de Biochimie EA 3796, Ufr de Pharmacie, Ifr 53 Biomolécules, 3, avenue du Maréchal Juin, F 51096 Reims Cedex.
Overexpression of a membrane glycoprotein (P170) represents the most common multidrug resistance (MDR) mechanism in cancer therapy. Specific autoantibodies to extracellular loops 1, 2 and 4 of murine P170 are elicited in mice using palmitoylated synthetic peptides reconstituted in liposomes with or without Lipid A and resuspended in alum. IgM antibodies are detected 14 days following the first injection and IgG1 become predominant after the third challenge.
View Article and Find Full Text PDFCancer Biother Radiopharm
February 2006
Department of Biotracer Medicine, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.
Purpose: The influence of serum components on the intracellular uptake of an 111In-oligonucleotide (ODN) against mdr1 mRNA was investigated in the murine leukemia cell line, P388/S, and its mdr1-overexpressed P388/R.
Methods: 111In-ODNs naked and vectorized with lipids were analyzed for binding with serum components using high-performance liquid chromatography (HPLC). 111In-ODN was incubated in albumin and transferrin solutions.
Eur J Nucl Med Mol Imaging
November 2004
Department of Biotracer Medicine (Nuclear Medicine), Kanazawa University Graduate School of Medical Sciences, 13-1 Takara-machi, Kanazawa, 920-8640 Japan.
Purpose: The feasibility of intracellular mdr1 mRNA expression detection with radiolabeled antisense oligonucleotide (ODN) was investigated in the murine leukemia cell line, P388/S, and its subclonal, adriamycin-resistant cell line, P388/R.
Methods: The expression level of mdr1 mRNA was analyzed by reverse transcription-polymerase chain reaction (RT-PCR). Existence of the multidrug resistance (MDR) phenomenon was assessed via cellular uptake of 99mTc-sestamibi (MIBI), a known substrate for P-glycoprotein.
Eur J Cancer
March 2004
IFR53, UFR Pharmacie, 3 avenue du Maréchal Juin, 51096 Reims Cedex, France.
Overexpression of the membrane glycoprotein (P170) represents the most common multidrug resistance (MDR) mechanism in cancer therapy. Specific auto-antibodies to extracellular loops 1, 2 and 4 of murine P170 were elicited in mice using palmitoylated synthetic peptides reconstituted in liposomes, with or without Lipid A, and resuspended in alum. IgM antibodies were detected 14 days following the first injection and IgG1 became predominant after the third challenge.
View Article and Find Full Text PDFInvest New Drugs
February 2002
Institute of New Antibiotics, Russian Academy of Medical Sciences, Moscow.
Previously, we have reported partial circumvention of P-glycoprotein (Pgp)-associated resistance to doxorubicin (Dox) in MCF7/R human breast carcinoma and P388/R murine leukemia cell lines by doxorubicin-14-O-hemiadipate (H-Dox) [Povarov L.S. et al.
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