Journal ArticleDOI
Expression of Multidrug Resistance Gene in Human Cancers
Lori J. Goldstein,Hanan Galski,Antonio Tito Fojo,Mark C. Willingham,Shinn Lian Lai,Adi F. Gazdar,Robert Pirker,Alexander A. Green,William M. Crist,Garrett M. Brodeur,Michael M. Lieber,Jeffrey Cossman,Michael M. Gottesman,Ira Pastan +13 more
TLDR
Evaluation of MDR1 gene expression may prove to be a valuable tool in the identification of individuals whose cancers are resistant to specific agents, and the information may be useful in designing or altering chemotherapeutic protocols in these patients.Abstract:
Chemotherapy has proven to be an effective treatment for the cure and palliation of some human cancers (Chabner, 1982). Some tumors, however, appear to be intrinsically resistant to chemotherapy. For cancers that can be treated with chemotherapy, based on the hypothesis that resistance to single agents occurs with high frequency, protocols involving multiple drugs with different intracellular targets have been designed. In many cases, such as acute lymphocytic leukemia and neuroblastoma (Simone et al., 1982), Hodgkin’s disease (De-Vita and Hellman, 1982), and germ cell cancers (Paulson et al., 1982), dramatic results have been achieved with such protocols. However, all too frequently relapse occurs after such therapy and the recurrent tumors are resistant to further chemotherapy. In effect, such tumors develop a multidrug resistance (MDR) phenotype that is very similar to the intrinsic resistance of some primary cancers.read more
Citations
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Multidrug resistance in cancer: role of ATP–dependent transporters
TL;DR: The ability to predict and circumvent drug resistance is likely to improve chemotherapy, and it has become apparent that resistance exists against every effective drug, even the authors' newest agents.
Journal ArticleDOI
Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line
Susan P.C. Cole,Gabu Bhardwaj,James H. Gerlach,J. E. Mackie,Caroline E. Grant,Kurt C. Almquist,Alistair J. Stewart,Ebba U. Kurz,A. M. V. Duncan,Roger G. Deeley +9 more
TL;DR: Reversion to drug sensitivity was associated with loss of gene amplification and a marked decrease in mRNA expression, and the mRNA encodes a member of the ATP-binding cassette transmembrane transporter superfamily.
Journal ArticleDOI
Mechanisms of cancer drug resistance
TL;DR: The most common reason for acquisition of resistance to a broad range of anticancer drugs is expression of one or more energy-dependent transporters that detect and eject anti-cancer drugs from cells, but other mechanisms of resistance including insensitivity to drug-induced apoptosis and induction of drug-detoxifying mechanisms probably play an important role in acquired anticancer drug resistance as mentioned in this paper.
Journal ArticleDOI
Disruption of the mouse mdr1a P-glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitivity to drugs
Alfred H. Schinkel,J. J. M. Smit,O. van Tellingen,Jos H. Beijnen,Els Wagenaar,L. Van Deemter,C. A. A. M. Mol,M. A. Van Der Valk,E. Robanus-Maandag,H te Riele,Anton Berns,Piet Borst +11 more
TL;DR: The findings explain some of the side effects in patients treated with a combination of carcinostatics and P-glycoprotein inhibitors and indicate that these inhibitors might be useful in selectively enhancing the access of a range of drugs to the brain.
Journal ArticleDOI
The cellular and molecular basis of hyperthermia.
Bert Hildebrandt,Peter Wust,Olaf Ahlers,Annette Dieing,Geetha Sreenivasa,Thoralf Kerner,Roland Felix,Hanno Riess +7 more
TL;DR: The direct cytotoxic effect of heat, heat-induced alterations of the tumor microenvironment, synergism of heat in conjunction with radiation and drugs, as well as, the presumed cellular effects of hyperthermia including the expression of heat-shock proteins (HSP), induction and regulation of apoptosis, signal transduction, and modulation of drug resistance byhyperthermia are discussed.
References
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Cancer : Principles and Practice of Oncology
TL;DR: Part I: Molecular Biology of Cancer Molecular Methods in Oncology Section 1. Amplification Techniques Section 2. RNA Interference Section 3. cDNA arrays Section 4. Tissue arrays Section 5. Cytogenetics Section 6. Bioinformatics Genomics and Proteomics Molecular Targets in oncology.
Journal ArticleDOI
Expression of a multidrug-resistance gene in human tumors and tissues
TL;DR: The results suggest that measurement of mdr1 RNA may prove to be a valuable tool in the design of chemotherapy protocols and controlled clinical studies will be required.
Journal ArticleDOI
Amplification of P-glycoprotein genes in multidrug-resistant mammalian cell lines.
TL;DR: Southern blot analysis of hamster, mouse and human DNA using this cDNA as a probe showed that P-glycoprotein is conserved and is probably encoded by a gene family, and that members of this putative family are amplified in multidrug-resistant cells.
Journal ArticleDOI
Human multidrug-resistant cell lines: increased mdr1 expression can precede gene amplification.
Ding-Wu Shen,Antonio Tito Fojo,Janice E. Chin,Igor B. Roninson,Nancy D. Richert,Ira Pastan,Michael M. Gottesman +6 more
TL;DR: Results suggest that increased expression of mdr1 mRNA is a common mechanism for multidrug resistance in human cells and that Activation of the m dr1 gene by mutations or epigenetic changes may precede its amplification during the development of resistance.
Journal ArticleDOI
Isolation and genetic characterization of human KB cell lines resistant to multiple drugs.
TL;DR: In this paper, human KB cell lines resistant to high levels of colchicine were isolated by several successive single-step selections, which resulted in cross-resistance to vincristine, vinblastine, adriamycin, actinomycin D, and puromycin.