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  • 1
    ISSN: 1573-0646
    Keywords: human tumor cell lines ; L1210 ; drug sensitivity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract L1210 leukemia cells, because of their rapid growth rate in suspension culture and high growth fraction, are ideally suited to screen in vitro for cytotoxic compounds. Although L1210 cells may mimic rapidly growing tumors, they have not been effective in selecting agents active against slow growing solid tumors. We expected that cell lines originating from human solid tumors, because of their slower growth rate and lower S phase fraction, would be more drug resistant than L1210. Therefore, we compared ten human tumor cell lines (5 melanomas, 4 colon carcinomas and 1 small cell lung carcinoma) to L1210 growth inhibition by 9 anti-tumor drugs. Not one human tumor cell line was consistently more resistant to all nine drugs than L1210 when the cells were exposed to drugs for about 2 doubling times. The drug sensitivity of 2 cell lines (L1210 and SK MEL 28) was again determined after a short term (2 hr) exposure and using growth inhibition and cell survival as end points. For both end points these two cell lines exhibited a random pattern of sensitivity to the drugs tested. Cell kill showed an order of sensitivity different than growth inhibition. The implication of these findings for drug-screening is discussed.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-0646
    Keywords: cytotoxicity ; prostaglandin D2 ; drug combinations ; B16 melanoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Prostaglandin D2 (PGD2) is lethal to murine and human melanoma cells at high doses, but synchronizes cells at G1 at non-toxic doses (2.5 or 5 μg/ml). We tested the lethality to B16 mouse melanoma cells of combinations of PGD2 with anticancer drugs. The drugs selected were mostly those used in treating human melanoma: actinomycin D, Bleomycin, BCNU, cis-platin, melphalan, 5-fluorouracil, and 1-β-D-arabinofuranosylcytosine (ara-C). PGD2 was combined with the drugs according to 3 different protocols: Protocol 1 An asynchronous culture was given a long term (24 hr) exposure simultaneously to PGD2 + drug. Combinations with Bleomycin, ara-C or melphalan were additive or slightly antagonistic whereas PGD2 plus actinomycin D was significantly antagonistic. Protocol 2 Cells synchronized in G1 by 24 hr PGD2 exposure were then given a short-term (2 hr) treatment with PGD2 + drug. Combinations with cis-platin, Bleomycin, BCNU or 5-fluorouracil were additive or slightly antagonistic, whereas melphalan and actinomycin D combinations were significantly antagonistic. Protocol 3 Cells were released from a PGD2-induced G1 block and were exposed to drug at different times during cell progression. Actinomycin D was antagonistic when added immediately after release from the G1 block, but was significantly synergistic when added 10 to 12 hr later. The effect of the combinations cannot be explained by available cell cycle or biochemical information. The antagonism between PGD2 and several of the drugs resembles the “cytoprotective” effect of PGD2 towards various noxious agents.
    Type of Medium: Electronic Resource
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