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Biomedical subjects

E Cadman

Publications and source records attributed to E Cadman.

65 records · Page 4Linked to original sources
PubMed1979

Mechanism of synergistic cell killing when methotrexate precedes cytosine arabinoside: study of L1210 and human leukemic cells.

Synergistic killing of L1210 cells occurs when methotrexate (MTX) is administered just before 1-beta-D-arabinofuranosylcytosine (Ara-C). This pehnomenon is dependent upon both the dose and time of exposure to MTX. Such increased killing of cells can be explained by the enhanced intracellular accumulation of Ara-C in cells exposed to MTX. This enhancement of Ara-C entry into cells was only observed when the dose of MTX was high enough (1, 10, and 100 muM) to result in free intracellular nondihydrofolate reductase-bound MTX. At the highest doses of MTX (10 and 100 muM) Ara-C triphosphate was increased eightfold and deoxycytidine triphosphate was decreased by 50%. Therefore, the maximum synergistic cell kill when MTX precedes Ara-C may be the consequence of greater inhibition of DNA polymerase by th;e increased Ara-C triphosphate in the presence of the decreasing natural substrate of this enzyme, deoxycytidine triphosphate. Enhanced Ara-C accumulation after administration of MTX was also observed in human acute myelogenous leukemia cells.

Animals↗
PubMed1977

Combination therapy for diffuse histiocytic lymphoma that includes antimetabolites.

Thirty patients with diffuse histiocytic lymphoma (DHL) were treated with one of three regimens that included cyclophosphamide, vincristine, methotrexate with citrovorum factor rescue, and cytosine arabinoside. Twelve patients had a complete response with a predicted 50% survival of at least 76 months. The medium survival of the 11 partial responders and seven nonresponders was 18 and 6 months, respectively. The addition of methotrexate and cytosine arabinoside may have a beneficial effect in therapy for DHL. From analysis of these results, there is reason to believe that efficacy may be partially dependent on the scheduling and dose of these two drugs.

Adolescent↗
PubMedDate not supplied

The enhanced transfer of drug-resistant genes in NIH-3T3 cells transformed by the EJras oncogene.

The spontaneous transfer of drug resistance genes has been shown to take place between cultured mammalian NIH-3T3 cells and occurs with a hierarchy of transfer efficiencies, transformed cells being more efficient than non-transformed cells. This experiment was accomplished by co-cultivating two NIH-3T3 sublines, each transfected by standard plasmid methods with a different drug resistance gene, subjecting the mixed population to double selection by adding both drugs to the mixed cell culture, and isolating single cells which were resistant to both drugs. The genes used were the neo gene and gpt gene which conferred resistance to the drugs G418 and mycophenolic acid, respectively. DNA analysis confirmed the presence of both resistance genes in the cells which were resistant to both drugs. The mechanism of this gene transfer was by cell fusion rather than by chromosomal DNA uptake. The efficiency of gene transfer, as indicated by the number of double-resistant colonies standardized by number of cells cultured, was much higher between two sublines of cells transformed by the EJras oncogene than between one transformed and one non-transformed subline, which in turn was higher than between two non-transformed sublines. The higher efficiency of gene transfer between the transformed cells also occurred when these cells were injected into nude mice, thus demonstrating that the same process occurred in vivo. It would appear that drug resistance genes may be transferred spontaneously in cultured mammalian cells by cell fusion, and that transformed cells have a higher efficiency of gene transfer compared to non-transformed cells.

Animals↗
PubMedDate not supplied

Misuse of scalp hypothermia.

Scalp hypothermia has been introduced to reduce the temporary epilation associated with certain cytotoxic drugs. This has improved compliance with drug delivery for some patients. It is currently not recommended for use in those tumors with a high prevalence of scalp metastasis, ie, leukemia and lymphoma. We have treated a patient for mycosis fungoides who demanded use of a "cooling cap" while undergoing consolidation chemotherapy. Cutaneous disease recurred on the scalp, with no other evidence of mycosis fungoides. Caution should be used in reducing drug delivery to the scalp while treating tumors manifesting cutaneous stem cell tumor nests.

Antineoplastic Agents↗