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Biomedical subjects

M Clynes

Publications and source records attributed to M Clynes.

14 recordsLinked to original sources

Multiple drug-resistance in variant of a human non-small cell lung carcinoma cell line, DLKP-A.

A 300-fold adriamycin resistant variant (DLKP-A) of the human lung squamous cell carcinoma line DLKP was established by stepwise selection in increasing concentrations of adriamycin. Different levels of cross-resistance were observed towards VP-16, VM-26, colchicine, vincristine and, somewhat unexpectedly, cis-platin. Resistance was stable for at least 3 months in culture in the absence of drug. P-glycoprotein overexpression was detected by immunofluorescence and Western Blotting, and a direct causal role for P-glycoprotein overexpression in the resistant phenotype was established by transfection with an mdr1 specific antisense oligonucleotide. A modified cryopreservation procedure was necessary for the resistant variant line. The resistant population displays clonal heterogeneity with respect to resistance level. A higher frequency of double minute chromosomes was observed in DLKP-A when compared with the parental cell line.

Antineoplastic Agents

Cytogenetic comparison of two poorly differentiated human lung squamous cell carcinoma lines.

This paper presents a cytogenetic analysis of two established but early-passage (passages 5 and 18) cell lines derived from histologically similar, poorly differentiated lymph node metastases of squamous cell carcinoma of the lung. The cell lines showed 3 shared marker chromosomes, del(1)(q11), del(2)(p11.1) and del(2)(q11.1). One of the lines (DLKP) had 8 additional markers including structural rearrangements such as translocations and isochromosomes. Five additional markers (including two deletions of chromosome 3) were found in DLRP. A notable feature of DLRP was the high incidence of telomeric association evident in the majority of metaphase plates. Over-representation of chromosome 7 was a characteristic feature of metaphases derived from DLKP, and identification of i(21q) in this cell line was an unusual finding. The results indicate significant cytogenetic heterogeneity between these early-passage cell lines derived from two apparently histologically similar tumors.

Carcinoma, Squamous Cell

Cytological differences between normal and malignant human cell populations in culture.

Cells from early-passage cultures of normal and malignant human tissues were analyzed for the presence of multiple nucleoli and tri- or multipolar mitoses; these properties are characteristic of malignant cell populations in tissue sections. For the cell types examined the presence of tri- or multipolar mitoses was characteristic of cells of malignant origin. Within epithelial cell populations, cells containing more than 4 nucleoli were found in populations of malignant but not of normal origin; this distinction did not apply to fibroblast populations. Large numbers of cells must be analyzed quantitatively to establish the distinctions described here, since they are properties characteristic of populations, not of individual cells. This approach may facilitate identification of normal and malignant cell populations in primary and early-passage culture.

Cell Nucleus

Establishment of two new multi-drug resistant variants of the human tumor line Hep-2.

Two multi-drug resistant variants of the human carcinoma line Hep-2 have been selected by adaptation to progressively increasing concentrations of adriamycin. In comparison to the wild-type Hep-2 cells, the variant lines both showed approximately 100-fold resistance to adriamycin, 10 to 20-fold resistance to the vinca alkaloids but only 2-3 fold resistance to VP-16 and VM-26. There was essentially no difference between wild-type and variant cells in regard to sensitivity to threosulfan and 5-fluorouracil. The drug-resistant phenotype is stable for at least 3 months in the absence of drug, and is partially reversible by concomitant treatment with Verapamil. Chromosomal abnormalities consistent with gene amplification were observed in one of the variant lines. Sensitivity of variant cells to adriamycin was enhanced following trypsin-EDTA treatment.

Antineoplastic Agents