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Biomedical subjects

B Barlogie

Publications and source records attributed to B Barlogie.

At least 271 records · Page 15Linked to original sources
PubMed1981

Biological properties of the human colonic adenocarcinoma cell line SW 620 grown as a xenograft in the athymic mouse.

The biological and cell kinetic properties of the poorly differentiated human colonic adenocarcinoma cell line SW 620 grown as xenografts in BALB/c athymic mice are described. The SW 620 cells consistently produced tumors when inoculated i.v., i.p., and s.c. The lowest cell inoculum requirements were seen i.p. where 10(7) cells produced a 100% incidence. Intravenous inocula (10(5) to 10(8) cells) produced microscopic lung colonies within 30 days, becoming macroscopic nodules after 60 days. Subcutaneous tumors exhibited a marked Révész effect, using a thromboplastic brain extract which increased both tumor incidence and growth rate. All SW 620 xenografts presented a poorly differentiated morphology with extensive necrotic foci. No metastatic involvement was noted in any murine tissues. No demonstrable levels of carcinoembryonic antigen were present in the sera of animals bearing s.c. xenografts greater than 5.0 cu cm. Early SW 620 xenografts (0.3 to 0.6 cu cm) exhibited a characteristically human cell kinetic profile (Tc congruent to 34 to 43 hr; Ts congruent to 22 hr), with a growth fraction of 30.5% as measured by the primer-available DNA polymerase-index and a high cell loss factor (45%). Among late xenografts (1.1 to 1.6 cu cm), the kinetic events noted were an increase in the Tc, cell loss and, unexpectedly, an increase in the primer-available DNA polymerase index. A colony formation assay was established with the use of mechanical mincing plus collagenase (150 IU/ml; 37 degrees; 30 min), which produced a mean plating efficiency of 33.6 +/- 7.2% (S.E.) for s.c. xenografts (range, 14.6 to 51.0%). The SW 620 xenograft model possesses the biological and cell kinetic profile of many human colonic adenocarcinomas in situ. These properties, coupled with the capacity for large-scale xenograft production, should provide a clinically relevant model for the screening of potential antitumor agents and procedures.

Adenocarcinoma↗
PubMed1981

The growth fraction of human myeloma cells.

Greater reductions of tumor load in patients with multiple myeloma may result from therapeutic strategies that are based on a better knowledge of growth kinetics. We have previously shown that the labeling index of myeloma cells remains unchanged when tumor mass is reduced and that the cells of relapsing patients have differnt biologic properties than the cells present before melphalan-prednisone therapy. This study investigated the growth fraction (GF) of myeloma cells at various disease stages using continuous i.v. infusions of tritiated thymidine. We studied 17 patients on 22 occasions (4 untreated, 2 unresponsive, 6 in remission, and 10 in relapse). All untreated an unresponsive patients and 5 of 6 patients in remission had a GF of less than 4%. GF was defined in these studies as the maximum percentage of labeled plasma cells exposed continuously to tritiated thymidine. Relapsing patients, with the most rapid tumor doubling times, had GF ranging from 14% to 83%. The plasma cell transit time through the proliferative compartment for all of the relapsing patients ranged from 6.6 to 11.9 days and the calculated intrinsic cell loss ranged from 50% to 86%. These findings support our model for the growth kinetics of multiple myeloma that assumes that the entire tumor mass issues from a small proportion of proliferating cells and that the growth kinetics of myeloma cells in relapsing patterns differ from those in untreated and unresponsive patients. Therapeutic trials with cycle-active agents need further investigation in selected relapsing patients who are likely to have a high growth fraction.

Female↗
PubMed1980

Flow cytogenetics of uncloned and cloned Chinese hamster cells.

Flow cytometry has greatly facilitated the routine use of DNA content as a cellular indicator of the stages of the cell cycle and ploidy. DNA content can also be used to distinguish individual chromosomes. Fluorescent staining of chromosome DNA was done with a combination of ethidium bromide and mithramycin in hypotonic solution. Subsequent detergent treatment of the cells with Triton X-100 facilitated chromosome isolation. DNA flow cytometry of chromosomes of four established uncloned Chinese master cell lines showed 10 to 12 major subpopulations of chromosomes with varying degrees of overlap in the range of low and intermediate DNA content. Cloning of B14F28 cells, the line with the largest heterogeneity in chromosome number and DNA content, considerably reduced the dispersion in chromosome number and improved the resolution of DNA content distributions. Thus, cloned cells with a relatively homogeneous karyotype permit better discrimination of chromosome subpopulations by DNA content than uncloned cells and provide a more sensitive system to study mutagenic effects.

Animals↗
PubMed1980

Persistence of EEG activity with prolonged induced hyperthermic fever.

Ten instances of deliberate systemic temperature elevation in the 41.5 degrees C to 42.2 degrees C range have been evaluated electroencephalographically, demonstrating decrease in predominant frequency and voltage. Persistence of electro-cerebral activity suggests that previous reports of electro-cerebral inactivity with elevated temperatures reflect indirect serious effects due to cardiovascular compromise with cerebral ischemia, rather than to a direct temperature-related loss of CNS electrical activity.

Anesthesia, General↗
PubMed1980

Flow cytometry of DNA content in human bone marrow: a critical reappraisal.

Because cytokinetic studies of the human bone marrow aspirate as a prognostic factor and as a monitor of drug perturbation are frequently inconsistent, we investigated reproducibility of DNA distribution measured by flow cytometry of DNA content in patients with morphologically normal bone marrow. In 15 patients, correlation was noted between DNA distributions simultaneously obtained on right and left iliac crest bone marrow aspirates (r = .588), although considerable variation in individuals was encountered. Much better reproducibility (r = .879) was achieved using bilateral core biopsy of bone marrow in these same patients. In 60 samples, comparison of DNA distribution between bone marrow aspirate and simultaneously obtained biopsy revealed higher relative proportions of S and G2 + M phase cells in biopsies (p less than 0.001), suggesting peripheral blood contamination of aspirate material. Brisk shaking of biopsy specimens in saline expelled a representative sample in the supernatant that could be subjected to simultaneous cytomorphological and cytokinetic analysis. To improve reproducibility of DNA content determinations in normal human bone marrow, bone marrow biopsy should be utilized.

Blood Cell Count↗
PubMed1980

Tumor cell phagocytosis. Its occurrence in a patient with medulloblastoma.

Phagocytosis was observed in tumor cells from a metastatic medulloblastoma to the bone marrow. Erythrocytes and leukocytes were seen in the cytoplasm of the tumor cells. Another abnormal finding was self-phagocytosis, in which tumor cells engulfed one another. The mechanism of tumor phagocytosis is not yet clearly understood. Only a few cases of erythrophagocytosis by epithelial tumor cells have been reported in the literature. To our knowledge, this is the first reported case of a medulloblastoma with hematophagocytosis.

Adult↗
PubMed1980

Characterization of hematologic malignancies by flow cytometry.

Flow cytometry of cellular DNA content revealed ploidy abnormalities in 15% of 170 patients with various leukemias, in 50% of 26 patients with malignant lymphomas, and in 68% of 110 patients with multiple myeloma, for an overall incidence of DNA content abnormality of 37% in 306 patients with hematologic malignancies. Since the incidence of ploidy abnormality in over 100 solid tumors exceeded 90%. DNA flow cytometry is also ideally suited to screen for bone marrow metastases. Cell separation by centrifugal elutriation was shown to permit enrichment of aneuploid cells, including one example where cells with abnormal DNA content were not recognized in the unfractionated sample. Biparametric measurements of acridine orange-stained cells for DNA and RNA content analysis were suitable to enhance the discriminatory power of flow cytometric detection of lymphoma and myeloma tumor cells in heterogeneous cell populations of bone marrow and lymph nodes. DNA/RNA measurements in leukemia, (the disease category with the lowest incidence of abnormal DNA mode) revealed a markedly higher mean RNA content in acute myeloid leukemia compared with normal or acute lymphoblastic leukemia bone marrow. While these different RNA content patterns were found in whole marrow, cell separation by centrifugal elutriation of normal marrow disclosed cell subpopulations of myeloid precursor cells with a RNA content pattern similar to that of unseparated AML marrow. Hence, the described differences in RNA content between normal and AML marrow seem to be related to the greater heterogeneity of differentiated cells in normal marrow and per se do not appear to be a unique feature of the leukemia disease process.

Bone Marrow↗
PubMed1980

In vitro thermochemotherapy of human colon cancer cells with cis-dichlorodiammineplatinum(II) and mitomycin C.

The thermosensitivity of human colon adenocarcinoma (LoVo) cells was investigated as a function of temperature and duration of heating in exponentially growing cultures. At 39-43 degrees, time-dependent survival followed a simple exponential function. Do values decreased progressively with a rise in temperature, from Do at 40 degrees = 38 hr to Do at 42 degrees = 17 hr to Do at 43 degrees = 1.5 hr. thus indicating relative thermoresistance of LoVo cells compared to Chinese hamster ovary cells. Dose-dependent 1-hr survival of LoVo cells treated with cis-dichlorodiammineplatinum(II) and mitomycin C was effectively modified when treatment was conducted under hyperthermic conditions. For both agents and cultures in exponential and stationary growth phases, hyperthermia abolished the initial shoulder portion and steepened the subsequent exponential part of the survival curves for dose-modifying factors at the 10% survival level of 1.5 to 2.0 at 41 degrees and 2.6 to 2.8 at 42 degrees. This significant enhancement of drug-induced cell kill by moderate hyperthermia suggests that thermochemotherapy with mitomycin C and cis-dichlorodiammineplatinum(II) should be tested clinically with both regional and total-body hyperthermia.

Adenocarcinoma↗
PubMed1980

Lethal and cytokinetic effects of mitomycin C on cultured human colon cancer cells.

The lethal and cytokinetic effects of mitomycin C (MC) as a function of drug concentration and exposure time were assessed in cultured human colon adenocarcinoma (LoVo) cells using colony formation to determine cell survival and DNA flow cytometry to examine cell cycle perturbation. MC evoked threshold-exponential type 1-hr dose-dependent survival curves in both exponential and stationary growth phases (Dq = 0.4 microgram/ml; Do = 1.0 microgram/ml). In exponentially growing cultures, a given exposure dose of MC induced equitoxic effects regardless of the specific drug concentration and exposure time used with uninterrupted treatment. However, dose fractionation experiments revealed the ability of LoVo cells to partially repair sublethal damage from MC exposure. Cell cycle progression was reversibly delayed or blocked in G2, S, and G1 phases in this order of sensitivity, with a frozen cycle distribution after greater than or equal to 24 hr treatment with 5 microgram of MC per ml. The reversible delay in S-phase traverse without a significant subsequent G2 block may be exploitable for administration of S-phase-specific drugs to maximize cell kill.

Adenocarcinoma↗
PubMed1980

Phase I study of 3-deazauridine in the treatment of adults with solid tumors.

A phase I trial of the uridine analog 3-deazauridine was undertaken in 44 adults with solid tumors. The drug was given as a 5-day continuous infusion repeated every 3-4 weeks. The dose-limiting toxic effect was granulocytopenia. Patients with prior nitrosourea therapy or extensive irradiation also had significant thrombocytopenia, and the lowest dose tested, 800 mg/m2/day, was excessive for this group. Mucositis was occasionally severe and was particularly marked in previously irradiated areas. Nausea was mild to moderate. There were isolated episodes of rash, headache, chest pain, and blurred vision. For patients without extensive prior therapy, the recommended dose is 1000 mg/m2/day. No complete or partial remissions were noted.

3-Deazauridine↗
PubMed1979

Cell-cycle phase-dependence of drug-induced cycle progression delay.

The effect of adriamycin on cell cycle phase progression of CHO cells synchronized into the various phases of the cell cycle by elutriation was investigated by high resolution pulse cytophotometry. Cells treated in all phases of the cell cycle showed delay in their subsequent progression. In addition to the wellknown block of cells in the G2-phase, a delay in passage of cells from G1 to S and a decreased rate of transit through the S-phase were observed. A broadening of the DNA distributions of the treated cells was observed after cell division indicating induction of chromosomal abnormalities.

Animals↗
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↗