Effect of liposomes sensitized with methotrexate-gamma-dimyristoylphosphatidylethanolamine on cells that are resistant to methotrexate.

@article{Kinsky1986EffectOL,
  title={Effect of liposomes sensitized with methotrexate-gamma-dimyristoylphosphatidylethanolamine on cells that are resistant to methotrexate.},
  author={Stephen C. Kinsky and K Hashimoto and Joan E. Loader and M. Knight and Daniel J. Fernandes},
  journal={Biochimica et biophysica acta},
  year={1986},
  volume={885 2},
  pages={
          129-35
        }
}
This study compares the ability of methotrexate and liposomes, in which the drug is anchored to the lipid bilayers via methotrexate-gamma-dimyristoylphosphatidylethanolamine, to inhibit proliferation of human leukemic cells (CEM/O) and cells derived from this line that are resistant to methotrexate because of either a defective transport system (CEM/MTX cells) or elevated levels of dihydrofolate reductase (CEM/R1 cells). Whereas CEM/O and CEM/MTX cells show a 120-fold difference in their… Expand
12 Citations
Inhibition of cell proliferation with antibody-targeted liposomes containing methotrexate-γ-dimyristoylphosphatidylethanolamine
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Although liposomal antitumor agents have no established role in the anticancer armamentarium at this stage, the information available suggests that they may improve the therapeutic index or broaden the applications of available antitumors and possibly act as carriers for newly designed liposome-dependent antitumour agents. Expand
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Dipalmitoylphosphatidylcholine (DPPC) liposomes were employed as membrane models for the investigation of the interaction occurring between methotrexate (MTX) and bilayer lipid matrix. Liposomes wereExpand
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Prospects for Liposomes as Drug Carriers
Liposomes are vesicles composed of concentric phospholipid bilayers that are formed spontaneously when an aqueous solution is added to a dried lipid film (Figure 1). Several types ofExpand
Binding of liposomes to human bladder tumor epithelial cell lines: implications for an intravesical drug delivery system for the treatment of bladder cancer.
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Data suggest that targeting of drugs to superficial bladder cancer can be achieved by the intravesical administration of PC/PS MLV, which appeared to be specific to tumor cells. Expand
Chemistry and biological activity of antifolates.
  • A. Rosowsky
  • Chemistry, Medicine
  • Progress in medicinal chemistry
  • 1989
Publisher Summary This chapter discusses the structural changes that have been made in each of the above regions of methotrexate (MTX), the synthetic chemical methods used in preparing MTX analogs,Expand
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Testing of liposomes with DMPE derivatives indicated that MTX-glyceroPE I was the most effective inhibitor of both cell proliferation and enzymatic activity, and novel use of thiamine pyrophosphate showed that this compound had no influence on inhibition of cell proliferation due to liposome. Expand
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Three (I-III) methotrexate derivatives of dimyristoylphosphatidylethanolamine by conjugation of the alpha and/or gamma glutamyl carboxyl groups of the drug with the amino function of the phospholipid are synthesized. Expand
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A stable mutant of human leukemia CCRF/CEM cells has recently been isolated which is transport resistant for methotrexate (MTX) and liposome encapsulation may allow such transport resistant tumor cells to become responsive to chemotherapeutic doses of MTX which are currently feasible in human clinical protocols. Expand
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TLDR
An N-hydroxysuccinimide ester of [3H]methotrexate has been employed to covalently label a specific binding protein that resides in the plasma membrane of L1210 cells, supporting a role for this protein in methotrexate transport. Expand
A methotrexate-resistant human breast cancer cell line with multiple defects, including diminished formation of methotrexate polyglutamates.
TLDR
These studies identify a new mechanism (diminished accumulation of MTX polyglutamates) associated with resistance to MTX and lend additional support to the hypothesis that the formation of these derivatives is an important determinant ofMTX cytotoxicity. Expand
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The demonstration of multiple routes for methotrexate efflux and their differential sensitivities to alterations in energy metabolism thus provides a basis for explaining previously described asymmetries between the influx and efflux of metotrexate in mouse leukemia cells. Expand
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Results support the hypothesis that methotrexate transport proceeds via an anion-exchange mechanism and provide evidence that anion substrates for this system can be identified by their ability to promote metotrexate efflux. Expand
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TLDR
The development of resistance to methotrexate (75-fold) was associated with a 20-fold increase of dihydrofolate reductase activity, and an elongated marker chromosome containing a homogeneous staining region not present in the parent line was revealed. Expand