Library

X
feed icon rss

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • Folate compounds  (1)
  • Key words 10-Propargyl-10-deazaaminopterin  (1)
  • efflux routes  (1)
  • 1
    Electronic Resource
    Electronic Resource
    A new analogue of 10-deazaaminopterin with markedly enhanced curative effects against human tumor xenografts in mice (1998)
    Springer
    Cancer chemotherapy and pharmacology 42 (1998), S. 313-318 
    Details
    ISSN: 1432-0843
    Keywords: Key words 10-Propargyl-10-deazaaminopterin ; Cytotoxicity ; Efficacy ; Human tumors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: These studies sought to evaluate the biochemical and cellular pharmacokinetic properties, cytotoxicity and antitumor efficacy of a new analogue of 10-deaza-aminopterin (PDX) against human tumors. Methods: Studies were conducted with a group of human tumor cell lines in culture examining PDX and other folate analogues as permeants for mediated membrane transport, as inhibitors of dihdrofolate reductase and as substrates for folylpolyglutamate synthetase. These same analogues were examined for their cytotoxicity following a 3-h pulse exposure, in experiments providing a value for IC50. Other studies with these analogues were conducted in nude mice bearing subcutaneously implanted human tumors. Treatment of the mice was initiated 4 days after implantation of the tumor using a schedule of administration of one dose per day for 5 days. The tumors were measured 6 days after cessation of therapy and compared to controls for assessment of response. Results: In the CCRF-CEM cell system, PDX was 2- to 3-fold less effective as an inhibitor of dihydrofolate reductase than aminopterin (AMT), methotrexate (MTX) or edatrexate (EDX) but much more effective as a permeant for one-carbon, reduced folate transport inward (PDX 〉AMT ≃ EDX 〉MTX) and substrate for folylpolyglutamate synthetase (PDX 〉AMT 〉EDX 〉MTX). As predicted by these results, PDX was 15- to 40-fold more cytotoxic than MTX and 3- to 4-fold more cytotoxic than the highly potent EDX following a 3-h pulse exposure in culture of CCRF-CEM cells and cells from a panel of three human breast and two human nonsmall-cell (NSC) lung cancers. The same relative differences were shown for the therapeutic efficacy of these three analogues at equitoxic doses in studies with the human MX-1 and LX-1 tumors and the human A549 NSC lung tumor xenografted in nude mice. On a schedule of qd × 5 given 3–4 days posttransplant, MTX was minimally active (modest tumor growth delay) against all three tumors. EDX was highly active (25–35% complete regressions and 5–10% cures) against the MX-1 and LX-1 tumors but very modestly active (no regressions) against the A549 tumor. In contrast, PDX was even more active (75–85% complete regressions and 25–30% cures) than EDX against the MX-1 and LX-1 tumors and highly active (30% complete regressions and 20% cures) against the A549 tumor. Conclusions: These studies showed significantly enhanced antitumor properties of PDX compared with MTX and EDX. Based upon these results, clinical trials of PDX in patients with metastatic breast and NSC lung cancer appear to be warranted.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002800050823
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 2
    Electronic Resource
    Electronic Resource
    Relationships between carrier-mediated transport of folate compounds by L1210 leukemia cells: Evidence for multiplicity of entry routes with different kinetic properties expressed in plasma membrane vesicles (1983)
    Springer
    The journal of membrane biology 75 (1983), S. 11-20 
    Details
    ISSN: 1432-1424
    Keywords: Folate compounds ; transport multiplicity L1210 cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary Various independent kinetic criteria for indicating multiplicity of carrier-mediated entry of folate compounds into L1210 cell plasma membrane vesicles are studied. We find a marked inconsistency between values for influxK m andK ix in reciprocal experiments measuring competition between various folate compounds as well as inconsistent effects of transloading shown for 5-formyltetrahydrofolate influx, but not folic acid influx. These results argue strongly against a one-carrier model for transport of folate compounds. The most straightforward interpretation of our data is that two distinct transport systems mediate entry of folate compounds in L1210 plasma membrane vesicles. If a two-carrier model is correct, then our data indicate that one of the carriers has low capacity and high affinity for folate coenzymes and methotrexate. This system is apparently negligible as a transport route for folic acid. Transtimulation of initial influx by substrates of the low capacity system is obtained following transloading with coenzymes but not by transloading with folic acid. Our data indicate that the second folate transport system postulated by the two-carrier model has a low affinity for all the folate compounds studied. Nevertheless, the putative second system is significant, especially for folic acid transport, because it has a much higher capacity than the first transport system. In contrast to the first system, transloading with any of the folate compounds studied had no effect on initial influx mediated by the second folate transport system. The two systems are also differentially inhibited bypCMBS, DIDS and SITS and the influxV max for the high-affinity/low-capacity system was altered in a vesicle preparation derived from a methotrexate resistant L1210 cell line.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01870795
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 3
    Electronic Resource
    Electronic Resource
    Effects of metabolic deprivation on methotrexate transport in L1210 leukemia cells: Further evidence for separate influx and efflux systems with different energetic requirements (1984)
    Springer
    The journal of membrane biology 78 (1984), S. 9-17 
    Details
    ISSN: 1432-1424
    Keywords: methotrexate ; transport ; L1210 cells ; nonidentical influx ; efflux routes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary Measurements of methotrexate transport in L1210 cells in the presence and absence ofd-glucose reveal that both influx and efflux are depressed in the absence ofd-glucose, whereas the steady-state accumulation of drug is enhanced. The reason for the increase in steady state is that the relative decline in efflux is greater than the decline in influx. Analysis of the concentration dependence of steady-state methotrexate accumulation ind-glucose-deprived cells indicates a linear relationship consistent with a one-carrier active transport model. Similar data in nondeprived cells is highly nonlinear and strongly supports the postulate that under physiological conditions influx and efflux of methotrexate are mediated by separate carrier systems. These results indicate that the efflux system, preferentially transporting methotrexate under normal conditions, cannot operate in the absence ofd-glucose, whereas the influx system is only partially inhibited under conditions of glucose deprivation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01872527
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...