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Biomedical subjects

B Drewinko

Publications and source records attributed to B Drewinko.

188 records · Page 11Linked to original sources

Peplomycin and bleomycin effects on human colon cancer cells.

The lethal effects of peplomycin and bleomycin on cultured human colon cancer cells (LoVo) were compared by using the technique of inhibition of colony formation. The survival of LoVo cells after treatment for 1 h with either peplomycin or bleomycin was characterized by a biphasic exponential curve. When the exposure time was extended to 24 h, both drugs produced much greater cytotoxic effects, with survival decreased to less than 0.10% for bleomycin and less than 0.02% for peplomycin. Both peplomycin and bleomycin, in a dose-dependent manner, inhibited the incorporation of thymidine into cells. On an equal-weight basis, the cytotoxicity of peplomycin (24-h exposure) was similar to that of bleomycin. Both agent also inhibited the incorporation of leucine and uridine after 24 h of drug exposure, but to a lesser extent than inhibition of thymidine incorporation. However, after 1 h of exposure, such inhibitory effects were minimal. These results demonstrate that prolonged peplomycin or bleomycin exposure produces greater cell-kill than shorter drug exposure. Schedules with continuous drug administration should be explored clinically.

Bleomycin↗

The heterogenous cytotoxic response of colon cancer cells is unrelated to phenotypic differentiation characteristics.

Six colon cancer cell lines segregated into three groups with distinct biological properties (i.e., morphological differentiation, DNA content, carcinoembryonic antigen production, etc.) were treated with ten antitumor drugs. Cytotoxic responses were heterogenous and not associated to biological grouping, in fact, for some drugs, the response of one member of the group resembled that of a member of another group rather than its group counterpart. Thus the most common phenotypic characteristics that identify colon cancer cells did not predict the cytotoxic response and do not appear useful for stratifying patients into categories with distinct responses to currently available chemotherapeutic agents.

Antineoplastic Agents↗

Failure of human myeloma cells to heterotransplant into the brain of athymic rats.

Sixty-four separate intracranial inoculations of bone marrow cells obtained from 26 patients with human myeloma were performed and the animals were kept under observation for 9-10 months. Samples were obtained from a heterogenous group of patients with diverse types of paraprotein production, clinical status, and response to treatment. Inocula size ranged from 3.5 x 10(5) nucleated cells to about 2 x 10(7), while the percentage of plasma cells varied from nondetectable to 90%. Only one animal (of 2) injected with an aliquot of the bone marrow aspirate from a patient developed a small, clinically undetectable tumor, noticed at the end of the observation period. No other animal developed tumors. Thus, our studies indicate that the intracerebral inoculation of human myeloma cells may not be a profitable means of establishing additional human myeloma cell lines.

Animals↗

Expression of transferrin receptors is unrelated to proliferative status in cultured human colon cancer cells.

Transferrin is an iron-carrying compound that stimulates cell growth and division by binding to specific receptors (TR) which are preferentially expressed by actively growing cells or by the malignant counterpart of normal cells. However, quiescent cells may not necessarily cease expressing TR. We evaluated TR expression by flow cytometric analysis utilizing a monoclonal antibody (OKT-9) specific for TR on six established human colon cancer cell lines with distinct degrees of phenotypic differentiation and growth rates at sequential stages of in vitro growth (exponential and stationary phase). There were no significant differences in the proportion of cells expressing TR among the fast and slow growing cell lines at any time point of the study, nor did the cultures change the proportion of TR positive cells in their transit from exponential into stationary phase of growth. Hence, direct measurements of TR expression in malignant cell populations may not provide a useful clinical marker to distinguish highly proliferative tumors from those with a slower growth resulting from a larger proportion of quiescent cells.

Antibodies, Monoclonal↗