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Biomedical subjects

B Drewinko

Publications and source records attributed to B Drewinko.

At least 145 records · Page 8Linked to original sources
PubMed1976

DNA histogram analysis of human hemopoietic cells.

The proliferative activity of human neoplasms may be an important determinant for therapeutic management. The advent of automated flow-through systems measuring cellular DNA content by means of fluorescence has considerably facilitated the analysis of cellular kinetics. Using a pulse cytophotometer ICP-11 (Phywe Co., Göttingen, Germany), three different fluorescent staining techniques for DNA histogram measurement on human hemopoietic cells were tested: mithramycin, ethidium bromide, and a combination of ethidium bromide and mithramycin. Employing the tritiated thymidine labeling index as reference standard for comparison with the DNA histogram-derived S-phase fractions, linear correlations were obtained using ethidium bromide alone and ethidium bromide in combination with mithramycin as staining techniques. The fluorescence intensity was increased fourfold to fivefold by the use of the two-dye combination, resulting in a substantial decrease in the coefficient of variation of DNA histograms to 1.5%-2%. This augmented histogram resolution is an important codition for detecting small-degree numeric chromosomal aberrations and discrete drug perturbation effects.

DNA↗
PubMed1976

Establishment of a human carcinoembryonic antigen-producing colon adenocarcinoma cell line.

A human carcinoembryonic antigen-producing colon carcinoma cell line has been established. The cells form acinar structures and signet ring cells. The lumen of the acini presents microvilli and a glycocalyx. Neighboring cells show desmosomes and terminal bars. The cells present an aneuploid karyotype with a modal number of 49. No marker chromosomes are found, although a significant proportion of cells show an altered A2 chromosome and an extra B. Exponentially growing cultures produce 54 ng of carcinoembryonic antigen/10(6) cells. Kinetic parameters are as follows: doubling time, 37 hr; mitotic index, 0.8%; labeling index, 31%; generation time, 30 hr; G1 phase, 7 hr; S phase, 18 hr; G2 phase, 5 hr; growth fraction 90%. This cell line, designated line LoVo, represents an in vitro model for human colon carcinoma.

Adenocarcinoma↗
PubMed1976

A comparison of the lethal effects of three nitrosourea derivatives on cultured human lymphoma cells.

The cellular effects of three nitrosourea derivatives were investigated on a human lymphoma cell line. The three drugs show similar threshold-type dose-response survival curves on asynchronous cells treated for 1 hr. Longer incubation periods result in rapid biological degradation for 1,3-bis(2-chloroethyl)-1-nitrosourea and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea, whereas, 1-(2-chloroethyl)-3-trans-4-methylcyclohexyl)-1-nitrosourea, remains cytotoxic after about 24 hr. Important differences were noted with respect to cell cycle dependency. The 1,3-bis(2-chloroethyl)-1-nitrosourea was more effective in early S and in G2 phase, whereas both 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea and 1-(2-chloroethyl)-3-trans-4-methylcyclohexyl)-1-nitrosourea were more effective in early S. 1,3-bis(2-chlrorethyl)-1-nitrosourea exerted a considerable degree of killing in G1. Cells were unable to recover from priming damage induced by all 3 nitrosourea derivatives. No synergistic effects were observed in combination with vitamin A.

Amphotericin B↗
PubMed1976

Cell cycle dependency of human sarcoma-associated tumor antigen expression.

An analysis of cell cycle-dependent expression of tumor-associated antigen was performed on a human neurosarcoma cell line (T2 cells). The expression of sarcoma-associated tumor antigen on T2 cells was detected using test sera obtained from sarcoma patients; control sera were from patients with nonsarcoma neoplasias and from normal donors. Results indicate a progressive increase in the antigenic expression beginning in late mitosis and early G1 with maximum expression in mid-G1. Antigenic expression declines to minimum levels in S and G2-phase. Mechanisms responsible for this cycle-dependent fluctuation are presently unknown.

Antibodies, Neoplasm↗
PubMed1976

The effect of adriamycin on the cell cycle traverse of a human lymphoid cell line.

The kinetic response of a human lymphoma cell line to adriamycin was analyzed by means of pulse cytophotometry. Depending on concentration and exposure time, cell cycle progression was delayed in G1, S, and G2 phases. There was a differential sensitivity for the interaction of adriamycin with the transit through these phases. G2 arrest could be induced by low concentrations of adriamycin, whereas the block in G1 was exerted only after long-term treatment with high concentrations and was completely reversible after drug removal. Delay in S-phase transit was transient in spite of continuous exposure to high concentrations of adriamycin. Thus, concentration and duration of treatment determined the magnitude of G2 arrest as well as onset and rate of G2 accumulation due to progression delay in G1 and S phases. Cell age had only little influence on the degree of subsequent G2 arrest. Irreversibility of the G2 block strongly suggests eventual cell death in G2 phase, which may be utilized as a predictive test for response to adriamycin in vivo.

Cell Division↗
PubMed1976

Comparison of in vitro methods to determine drug-induced cell lethality.

In proliferating cell populations, the inability to reproduce indefinitely is the only relevant criterion to assess cell lethality. The in vitro colony formation technique (CF) used to determine reproductive death is, however, too slow and has several technical limitations. For finding suitable, more rapid techniques that assessed drug-induced cell killing, a human lymphoma cell line was exposed in vitro to increasing concentrations of adriamycin, bleomycin, and 1,3-bis(2-chloroethyl)-1-nitrosourea for 1 hr. Survival was assayed immediately after treatment and at regular intervals thereafter. Data from CF were compared to those resulting from the following tests: doubling time, labeling index, dye exclusion, 51Cr release, and rate of [3H]thymidine uptake (scintillation index). Dye exclusion and 51Cr release failed to demonstrate any killing effect for the 3 drugs. The percentage of killing calculated from doubling time determinations, although dose dependent, failed to correlate with CF. Scintillation and labeling index values displayed similar temporal fluctuations but were not clearly dose dependent and did not correlate with CF. Thus, CF appears as the most reliable, dose-dependent index of cell lethality. Tests that measure metabolic death grossly overestimate or underestimate killing activity induced by 3 of the most effective antitumor drugs.

Antineoplastic Agents↗
PubMed1976

Kinetic response of human lymphoid cells to adriamycin-DNA complex in vitro.

The lysosomotropic agent adriamycin-DNA complex was analyzed for its effect on cell cycle progression of human lymphoid cells in culture by means of pulse cytophotometry. Complexing to DNA slightly reduced the perturbation effects previously reported for adriamycin alone. The major kinetic response was a G2 block, the magnitude and duration of which was dependent on drug concentration and duration of treatment. When high drug concentrations were maintained for a prolonged period of time, an additional, completely reversible block in G1 phase or at the G1-S boundary was observed, accounting for two-step G2 accumulation curves. Cell age markedly influenced the magnitude of G2 accumulation in that treatment of cells in S and early G2 phase was most effective.

Cells, Cultured↗
PubMed1976

Pulse cytophotometric analysis of synchronized cells in vitro.

Pulse cytophotometry is a reliable rapid technique rendering a detailed direct analysis of the distribution of cells in G1/10, S, and (G2 + M) phase. We used a Phywe pulse cytophotometer ICP 11 to monitor cell cycle progression of synchronized human lymphoma cells in culture. With mithramycin as the fluorescent dye, sample processing is fast and provides DNA histograms of high resolution and precision. Results obtained from these histograms are in excellent agreement with those obtained by conventional techniques. Thus, we have established the conditions necessary to apply pulse cytophotometry for studies of drug-induced cytokinetic effects on this cell line.

Cell Division↗
PubMed1976

Survival and cycle-progression delay of cultured human lymphoma cells treated with 1-propanol, 3,3'-iminodi-, dimethanesulfonate (ester), hydrochloride (Yoshi 864).

Asynchronous human lymphoma cells treated for 1 hour with increasing concentrations of 1-propanol, 3,3'-iminodi-, dimethanesulfonate (ester), hydrochloride (Yoshi 864) revealed a shouldered survival curve typical of the effects of alkylating agents and of ionizing radiation on this cell line. Yoshi 864 was unstable under the conditions of treatment, its killing effect being reduced by 50% after only 4 hours. Synchronized cells showed stage-dependent sensitivity: early-S, late-G2, and late-G1 phases were the most sensitive while mid- and late-S and early-G2 phases were relatively insensitive. Yoshi 864 induced a concentration- and incubation time-dependent delay in the transit of asynchronous cells through G2 phase, with maximum accumulation values obtained after 12 hours of incubation with 100 mug/ml. This effect was largely reversible and no further kinetic changes were noted in the progeny of treated cells. Incubation of synchronized cells for 1 hour with 100 mug/ml demonstrated a block in G2, the manifestation of which during the lifespan of the treated cell or in its immediate progeny was cell-cycle dependent. Thus, cells treated in G1, early-, and mid-S phases showed a delay in the subsequent G2 phase while cells treated in late S and in G2 manifested this effect in the G2 phase of the immediate progeny. There was no correlation between this blocking effect in G2 with cell survival assessed by colony formation. Yoshi 864, although a rather inefficient killing drug, may represent a useful chemical synchronizing agent.

Cell Division↗
PubMed1976

Pulse cytophotometric analysis of cell cycle perturbation with bleomycin in vitro.

The kinetic response of a human lymphoma cell line to bleomycin has been analyzed, using an ICP-11 pulse cytophotometer. Bleomycin induced a delay of the cell-cycle traverse in G2 phase, the extent and recovery of which depended on drug concentration, exposure time, and cell cycle stage where treatment was applied. Different phase sensitivity for lethal damage (G2 phase) and kinetic response (early S phase) were documented. Recovery from G2 block did not predict for unimpaired reproductive capacity.

Bleomycin↗
PubMed1976

Combination chemotherapy in vitro with adriamycin. Observations of additive, antagonistic, and synergistic effects when used in two-drug combinations on cultured human lymphoma cells.

Adriamycin was paired with 12 other chemotherapeutic drugs in a search for possible synergistic pairs. Cell lethality was investigated by the colony-formation method utilizing a long-term human lymphoma cell line. Addative effects were noted with CCNU, ara-C, prednisolone, DDP, VP-16, and Yoshi, and mild synergistic effects with BLEO and CS. Adriamycin reduced the killing ability of BCNU and MeCCNU when applied simultaneously. This antagonistic effect was canceled by sequential incubation with each drug. It appears that no significant synergism can be expected by simultaneous pairing of adriamycin with some currently available chemotherapeutic agents.

Antineoplastic Agents↗
PubMed1976

Cell cycle dependency of tumor antigens.

There is now substantial evidence that suggests that tumor antigen expression is cell cycle dependent. This information has been obtained from a wide variety of tumor systems. The G1 phase of the cell cycle has been implicated by a number of investigators as the point of maximal antigen appearance. In this presentation, we are concerned with a human sarcoma-associated tumor antigen and its cell cycle-dependent appearance. Sarcoma-associated tumor antigen is a membrane antigen present on cultured human neurosarcoma cells (T2-cells). Although the underlying mechanisms responsible for cell cycle-dependent expression are unclear, several possible interpretations are offered.

Antigens, Neoplasm↗
PubMed1975

Clinical and morphological correlations in acute promyelocytic leukemia.

Thirty adults with acute leukemia and greater than 20% bone marrow infiltrate by promyelocytes were studied. Eighteen patients had acute promyelocytic leukemia (APML) as defined by the presence of malignant promyelocytes, and the remaining 12 patients had acute myelocytic leukemia (AML) with an elevated percentage of normal promyelocytes. Malignant promyelocytes were characterized by abundant, abnormal, cytoplasmic granules, by Auer rods in meshwork pattern, and by splinter cytoplasmic granulations and dilatation of the cisternae of endoplasmic reticulum. Patients with APML had, in general, greater than 35% bone marrow infiltrate by promyelocytes. The degree of bone marrow infiltrate by these cells correlated with the clinical status of the patients. Diffuse intravascular coagulation with bleeding occurred in 61% of patients with APML, and the bone marrows of these patients had greater than 50% promyelocytes. No coagulation abnormalities were seen among patients with elevated bone marrow promyelocytes infiltrate and without APML. Coagulation abnormalities in patients with APML were only corrected by controlling the leukemia itself. When this occurred, patients with APML had an excellent rate of complete remission, and the duration of remission and survival were comparable to the results obtained in adults with AML.

Adult↗
PubMed1975

Receptors for IgG and complement in human spleen lymphoid cells. Preferential binding of particulate immune complexes through complement receptors.

Human lymphoid spleen cells attached to Petri dishes by poly-L-lysine bind 51Cr-labeled erythrocytes coated with IgG antibodies or complement but not uncoated erythrocytes or those coated with IgM antibodies. The number of erythrocytes bound through complement receptors is several times larger than that bound through IgG receptors. Increasing up to five times the number of IgG molecules on the red blood cells only leads to a slight increase of binding. However, the addition of complement to the IgG-coated erthrocytes increases 10 times the binding to spleen cells, even in the presence of an excess of normal IgG. These results can be explained by postulating that there is a larger number (or greater affinity) of spleen cell receptors for complement than that of spleen cell receptors for IgG.

Antigen-Antibody Complex↗
PubMed1975

IgG-dependent clearance of red blood cells in IgG myeloma patients.

Red blood cells sensitizied with IgG antibodies are rapidly cleared from the circulation of myeloma patients, in spite of serum IgG concentrations several times higher than normal. In contrast, in vitro phagocytosis and cytotoxicity of IgG-sensitized erythrocytes are inhibited by dilutions of normal fresh serum. It is concluded that the current explanantions derived from in vitro experiments are insufficient to explain the IgG-dependent clearance of red blood cells.

Aged↗