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Biomedical subjects

B Drewinko

Publications and source records attributed to B Drewinko.

At least 19 recordsLinked to original sources
PubMed1989

Effect of donation time on platelet concentrates and fresh-frozen plasma. An in vitro study.

To investigate the effect of donation time on the quality of blood components, we measured the platelet count and pH on platelet concentrates, and the factor V and VIII:C levels and fibrinopeptide A concentration on fresh-frozen plasma by duration of donation time. Platelet concentrates and fresh-frozen plasma were classified into three groups according to donation time: group 1, less than 10 min; group 2, 10-15 min, and group 3, longer than 15 min. Mean platelet counts of platelet concentrate were: group 1, 8.6 +/- 2.5 (in x 10(10], group 2, 8.1 +/- 2.6, and group 3, 6.5 +/- 3.2 (p less than 0.05). The same pH was maintained in all three groups. The fibrinopeptide A concentrations in groups 1 and 2 were 24 +/- 53 and 169 +/- 64 ng/ml, respectively, while in group 3 all were greater than 200 ng/ml, indicating correlation of a higher fibrinopeptide A level with longer donation time. Although a higher fibrinopeptide A level indicated a greater degree of thrombin generation, assays of factors V and VII:C did not show decreased activity in groups 2 and 3.

Antigens↗
PubMed1986

Potential drugs for elimination of acute lymphatic leukemia cells from autologous bone marrow.

Five drugs, selected because of minimal in vivo myelotoxicity, have been investigated for inhibition of the growth of three acute lymphatic leukemia-derived cell lines. Granulocyte-macrophage colony-forming units (GM-CFU) inhibition with these five drugs after 60-min incubation was first established. Drug concentrations giving up to 90% kill of GM-CFU were then used. Spirogermanium and L-asparaginase did not have an effect on any of the three cell lines under the culture conditions tested, while 4-hydroperoxycyclophosphamide (4-HC) and vincristine inhibited the growth of all three cell lines tested, and bleomycin inhibited the growth of two cell lines. In addition to 4-HC, bleomycin and vincristine should be considered as possible agents in eliminating leukemic cells from autologous marrow grafts. These drugs also deserve further investigation in clonal systems.

Antineoplastic Agents↗
PubMed1986

New monoclonal antibodies against colon cancer-associated antigens.

Established human colon cancer cells with distinct degrees of differentiation (LoVo, well-differentiated; SW620, intermediate differentiation; and SW1116, poorly differentiated) were used to produce monoclonal antibodies (MoAbs) by standard hybridoma techniques. Specificity was tested by an enzyme-linked immunosorbent assay against human foreskin cells, 7 established human colon cancer lines, a panel of 17 established human tumor lines of different histological origins, purified carcinoembryonic antigen, panels of red blood cells, and a suspension of lymphocytes obtained from 30 random normal donors. MoAb LoVo-F4 3E4/1A1/2E10 (MoAb F4/2E10) reacted with five colon cancer lines and only slightly with MCF-7 cells (estrogen receptor positive breast carcinoma). MoAb LoVo-F4 3E4/1A1/5C10 also reacted with the previous five colon cancer lines and with two gastric cancer lines. A MoAb obtained with a LoVo 3 M KCl membrane extract reacted exclusively with LoVo cells. MoAb SW620-F1 4E5/1A3 reacted with only three colon cancer cell lines and an estrogen receptor negative breast cancer line. MoAb SW1116-F2 1E3/1A1 reacted with four colon carcinoma cell lines, one gastric cancer line, MCF-7 cells, and a lung cancer line. MoAb SW1116-F2 1F3/1B1 reacted intensely with purified carcinoembryonic antigen and with every carcinoembryonic antigen-producing cell line available in our laboratory. Further studies concentrated on the immunoglobulin G1 MoAb F4/2E10. We demonstrated that the purified MoAb did not inhibit binding of MoAb CA19-9 to any colon Ca lines and reacted with fresh human colon carcinoma specimens regardless of whether they were processed by cryostat or paraffin embedding after fixation in formalin for 24 through 96 h. Using the peroxidase-antiperoxidase technique, MoAb F4/2E10 did not react with 23 normal adult and 18 fetal (less than 3 months old) human tissue specimens. When tested on 312 specimens of diverse histological origins and diseases, the MoAb was positive in 57 of 62 colorectal cancers, in 12 of 19 villous adenomas, in 5 of 7 adenomatous polyps, and in 10 of 12 cases of ulcerative colitis. With the exception of 2 of 15 cases of Crohn's disease that were slightly positive, all tissues from nonmalignant diseases (regardless of histological origin) were consistently negative. There was only weak reactivity in 2 of 18 breast cancers, 7 of 21 squamous cell carcinomas, 4 of 27 lung tumors, 1 of 13 kidney carcinomas and in 7 miscellaneous tumors.(ABSTRACT TRUNCATED AT 400 WORDS)

Antibodies, Monoclonal↗
PubMed1986

Kinetics and mechanism of the 1-beta-D-arabinofuranosylcytosine-induced potentiation of cis-diamminedichloroplatinum(II) cytotoxicity.

Certain aspects of the potentiation induced by 1-beta-D-arabinofuranosylcytosine (ara-C) on cis-diamminedichloroplatinum(II) (cis-DDP) cytotoxicity were investigated. The time dependency of additions of ara-C and cis-DDP was established by allowing cells to grow for various intervals in fresh medium following the removal of one agent before adding the second one. ara-C had no potentiating effect on cis-DDP toxicity when given to the cells before the addition of cis-DDP. When the experiment was reversed so that cis-DDP was added first and ara-C second, a slight potentiating effect was observed even if the drugs were added 4 h apart. The optimal toxic effect was obtained when ara-C and cis-DDP were added together. Continuous exposure of cells to concentrations of ara-C and cis-DDP 10 times lower than those used in pulse treatment experiments resulted in an additive rather than a synergistic effect. ara-C, unable to kill cells in pulse treatment, killed 96% of the cells after 24 h of continuous incubation. Thiourea was able to prevent the cytotoxic effect of cis-DDP in a concentration-dependent manner when given to the cells immediately following their treatment with cis-DDP; at 0.1 M thiourea, the cytotoxic effect of cis-DDP was almost completely prevented. Similar results were obtained when the cells were exposed to a combination of cis-DDP and ara-C. In this case, 0.1 M thiourea resulted in over 80% survival of cells treated with the drug combination. Thiourea had to be added to the cells either together with cis-DDP or immediately following removal of the drug in order to completely prevent the cytotoxic effect. A similar time factor was involved when cells were treated with a combination of cis-DDP and ara-C before their exposure to thiourea, but in this case thiourea was only able to prevent completely the cytotoxic effect when added simultaneously with the drug combination. In other experiments, the effect of thiourea on cis-DDP-induced DNA cross-linking was measured by the alkaline elution technique. Thiourea was capable of preventing DNA cross-link formation both in cells treated with cis-DDP alone, and in cells exposed to the combination of cis-DDP and ara-C These observations further support the contention that ara-C potentiates cis-DDP cytotoxicity by increasing the ability of the platinum compound to form earlier, more stable DNA cross-links regardless of whether it is present in free or monoadducted form.(ABSTRACT TRUNCATED AT 400 WORDS)

Cell Line↗
PubMed1979

Effects of time, platelet concentration, and sex on the human platelet aggregation response.

The platelet aggregation responses induced by adenosine diphosphate (ADP) and collagen were characterized by parameters defining rate and extent of reaction. Values were compared on the basis of platelet concentration, time elapsed between sample collection and test performance, and sex of donors. Rate and extent of aggregation varied as a function of platelet concentration. Maximal responses were obtained for platelet concentrations greater than 100,000/microliter. Results from samples processed after 90 min of incubation at room temperature were consistently and significantly lower than those obtained from samples processed immediately. ADP-induced aggregation responses elicited by samples from male and female normal donors differed significantly. This indicates that comparisons between normal and patient results should be made with sex-matched individuals to avoid erroneous interpretations.

Adenosine Diphosphate↗
PubMed1979

Flow cytometric analysis of DNA content for ploidy determination in human solid tumors.

Flow cytometric studies of cellular DNA content were conducted in 26 patients with a variety of neoplasms. Cell dispersal was achieved with pepsin treatment, and a combination of ethidium bromide and mithramycin was used as DNA specific staining procedure. All measurements were conducted with a new sheath flow chamber in a PHYWE ICP 11 pulse cytophotometer. All but one patient with multiple myeloma had unimodal tumor cell DNA distributions. With human granulocytes as reference standard, 24 of 26 tumors were aneuploid; and of these, 23 showed varying degrees of hyperdiploidy. Except for one patient, ploidy abnormalities were stable on repeat examination.

Aneuploidy↗
PubMed1979

Effects of cis-dichlorodiammineplatinum(II) on human colon carcinoma cells in vitro.

The lethal effects of cis-dichlorodiammineplatinum(II) were investigated on an established human colon carcinoma cell line. cis-Dichlorodiammineplatinum(II) was one of the most efficient antineoplastic agents tested thus far on this human colon carcinoma cell line. Survival of exponentially growing cells exposed to increasing concentrations of the drug (both in medium or in Hanks' balanced salt solution) was of the threshold exponential type (Dq = 1.2 microgram/ml, 1 hr; Do = 3.5 microgram/ml, 1 hr). Stationary-phase cells were extremely sensitive to the drug, and the survival curve demonstrated a simple exponential pattern (Do = 3.9 microgram/ml, 1 hr). Long-term exposure to low concentrations of cis-dichlorodiammineplatinum induced a high degree of killing, with only 0.5% of the cells surviving after incubation for 24 hr with 2 microgram/ml. Cells were unable to recover from potentially lethal or sublethal damages induced by the drug.

Adenocarcinoma↗
PubMed1979

Response of exponentially growing, stationary-phase, and synchronized cultured human colon carcinoma cells to treatment with nitrosourea derivatives.

The lethal effects of two nitrosourea derivatives, 1,3-bis(2-chloroethyl)-1-nitrosourea and 4-[3-(2-chloroethyl)-3-nitrosoureido]-cis-cyclohexanecarboxylic acid, on a continuous line of human colon carcinoma cells (LoVo cells) were investigated. The survival response of exponentially growing and stationary-phase LoVo cells to both drugs were of the threshold exponential type. Survival was identical whether drugs were dissolved in medium or in Hanks' balanced salt solution. In contrast to previous results obtained for human lymphoma cells, 1,3-bis(2-chloroethyl)-1-nitrosourea exerted a progressively greater killing effect on LoVo cells as the incubation time was prolonged, while 4-[3-(2-chloroethyl)-3-nitrosoureido]-cis-cyclohexane-carboxylic acid, under similar circumstances presented decreased lethality in comparison to both 1,3-bis(2-chloroethyl)-1-nitrosourea and the effect previously observed for the lymphoma cells. Although no recovery from potentially lethal damage was noted for both exponentially growing and stationary-phase cells treated with each agent, in split-dose experiments, LoVo cells were able to recover from sublethal damage. No significant cell cycle stage dependent differences in killing ability were observed for the two agents.

Carmustine↗
PubMed1979

In vitro cytokinetic response of human colon cancer cells to cis-dichlorodiammineplatinum(II).

The cytokinetic response of a human colon carcinoma cell line to cis-dichlorodiammineplatinum(II) was investigated using flow cytometry of DNA content, autoradiography after pulse and continuous tritiated thymidine exposure, and mitotic accumulation after continuous Colcemid treatment. With increasing concentration and exposure time, cis-dichlorodiammineplatinum(II) delayed and then blocked cycle traverse in S and G2 phases. After prolonged treatment with high concentrations of cis-dichlorodiammineplatinum(II), an additional block in G1 or at the G1-S boundary was established. Irreversibility of cell cycle distribution changes after prolonged observation periods suggests cell death in G2, S, and G1 compartments.

Cell Cycle↗
PubMed1979

Combination chemotherapy in vitro. IV. Response of human colon carcinoma cells to combinations using cis-diamminedichloroplatinum.

Combination effects of cis-dichlorodiammine platinum (II) (DDP) paired with 12 other antineoplastic agents were investigated on a human carcinoembryonic antigen producing colon carcinoma cell line in vitro. DDP was effective in increasing the killing efficiency of many different drugs. Supraadditive effects were noted with hydroxyurea, bleomycin, cis-acid, BCNU, adriamycin and mitomycin C, and a marked synergistic effect was noted with ara-C. DDP displayed simple additive effects wit 5-fluorouracil (5-FU), Ftorafur and methotrexate, and subadditive effects in simultaneous combination with vincristine. In view of its powerful cytotoxic effects on this particular cell line and of the supraadditive effects of its combinations with nitrosoureas and mitomycin C, DDP appears as a potentially useful antineoplastic agent for combination therapeutic regimens for human colon carcinoma.

Antineoplastic Agents↗
PubMed1978

A computer-based reporting system for bone marrow evaluation.

A computerized system of reporting results of bone marrow examination has been implemented at The University of Texas System Cancer Center, M. D. Anderson Hospital and Tumor Institute, since 1975. All results are entered via the keyboard of cathode-ray tube (CRT) consoles and are instantly available to the attending physician in CRTs strategically located throughout the institution in patient-related areas. Differential counts are available within two to three hours after aspiration. Description of clot sections and smear, diagnosis, and differential diagnosis are completed within 24 hours. Permanent reports are also printed by the computer at regular intervals during the day. The physician can ask the computer for results on a given day or for a cumulative summary displayed in tabular or plot form. This system has proven efficient and rapid, not only for direct reporting of bone marrow examination results but also for storage and retrieval of patient information.

Bone Marrow Examination↗
PubMed1978

Prognostic significance of morphologic and cytochemical markers in adult acute leukemia.

Survival times in 100 cases of acute leukemia (74 granulocytic, 14 lymphocytic, and 12 undifferentiated) were correlated with classic morphologic and cytochemical criteria. The 14 patients who had lymphocytic leukemia had significantly longer survival compared with the two other groups. Undifferentiated leukemias had a shorter survival time than granulocytic leukemias. Several subclasses of granulocytic leukemias were formed according to the presence or absence of Auer rods and the percentage of peroxidase-positive blasts. Neither of these two features significantly influenced the survival of these patients. In the lymphocytic leukemia group, PAS-positive and negative leukemias had similar survival expectancies. It is concluded that division into lymphocytic and nonlymphocytic leukemias is still helpful in predicting survival times of patients who have acute leukemia, but that further subclassification of these groups based on the presence or absence of Auer rods and the percentages of peroxidase-positive blasts is of no additional benefit.

Adolescent↗