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Biomedical subjects

W M Gallmeier

Publications and source records attributed to W M Gallmeier.

94 records · Page 6Linked to original sources
PubMedDate not supplied

Randomized trial in advanced breast cancer using combination chemotherapy with or without C. parvum; preliminary results.

In a prospectively randomized cooperative study patients with metastatic breast cancer were treated with or without Corynebacterium parvum (C.p.)5 mg/sc/m2 on day 1 in addition to CAO/CMF (Cyclophosphamid (C) 150 mg/m2/d per os X 5 d and Adriamycine (A) 50 mg/m2 i.v. d 1 and Oncovin (O) 1.0 mg/m2 i.v. d 1. 6 CAO-cycles q 28 days later were followed by monthly CMF cycles q 28 d with Cyclophosphamide (same dose), Methotrexate 30 mg/m2 i.v. 1 and 5-fluorouracil 600 mg/m2 i.v. d 1). 76 patients entered the study until January 1, 1977. The patients' characteristics (age, cytostatic pretreatment, tumor free interval, metastatic sites and mean doses of CA) were well balanced in the two groups. The lowest values of WBC and platelets on d 14 of the monthly CAO-cycles show a mean nadir of 1,630/mm2 and 122'850/mm3 respectively in the C.p.-group and of 1,890/mm2 and 141'760/mm3 in the group without C.p. GI-toxicity was seen more frequently in the C.p. group. An improvement of symptoms was observed in 88% of the C.p.-CAO/CMF treated group and in 77% of the group without C.p. Complete and good partial remissions (greater than 50% tumor size reduction) were seen in 53% of the CAO-C.p. treated patients and in 34% of the patients in the control group without C.p. Survival data presently show a trend of improvement by the addition of C.p. to the CAO-CMF-chemotherapy regimen.

Breast Neoplasms↗
PubMedDate not supplied

Granulocyte-macrophage colony-stimulating factor (GM-CSF) reduces the density of stem cell factor receptors (c-kit oncogene product) on a GM-CSF-dependent human myeloid cell line.

By employing a monoclonal antibody against the stem cell factor receptor (SCF-R), c-kit oncogene product, we analysed in flow cytometric technique the density of SCF-R on GM/SO cells which were incubated under various culture conditions. These experiments revealed that there is an inverse correlation between the SCF-R density on the cells and the doses of granulocyte-macrophage colony-stimulating factor (GM-CSF) in culture medium; the lower the dose, the higher the density of SCF-R on the cells. More detailed analyses showed that, in contrast to SCF which rapidly downregulates its own receptor, GM-CSF does not alter the measurable level of SCF-R in an exposition period of 60 minutes, which suggests that the internalization or shedding of the receptor is not the mechanism of action. Since the most striking difference regarding density of SCF-R between GM-CSF-treated and untreated cells was observed on day 2, the modulation of c-kit oncogene protein by GM-CSF likely occur prior to expression of protein onto the cell surface. In order to exclude the possibility that altered cell viability due to insufficient GM-CSF content in culture medium might be responsible for the increased SCF-R densities on GM-CSF-dependent cells, we subsequently generated a GM-CSF-independent subclone which still responded to GM-CSF as well as the dependent did. The experiments carried out with this subclone confirmed the results presented above. Thus our data suggest that GM-CSF is directly involved in the regulation of SCF receptor density on GM/SO cells.

Antibodies, Monoclonal↗
PubMedDate not supplied

Regulation of the density of the stem cell factor receptor (c-kit) by tumor necrosis factor alpha on a human myeloid cell line.

The GM/SO cell line bears a high level of stem cell factor receptors (SCF-R) i.e. c-kit protein, and therefore constitutes a potential model for studying the regulation of this crucial receptor on myeloid cells. In this study we evaluated the effect of tumor necrosis factor alpha (TNF-alpha) on the expression of SCF-R by flow cytometry. In contrast to 1 hour of preincubation, the experiments carried out after 24 hours preincubation revealed that TNF-alpha, if added alone, reduced the density of SCF-R on GM/SO cells in a dose-dependent manner. However, if combined with GM-CSF, which per se downregulates the SCF-R on these cells as well, TNF-alpha antagonized the effect of GM-CSF and slightly increased the density of SCF-R. Yet the cells incubated for 24 hours in medium without cytokines invariably expressed a higher level of SCF-R than the cells incubated in the presence of TNF-alpha and GM-CSF, either alone or in combination. In contrast to these cytokines, stem cell factor (SCF), which was also tested simultaneously in all experiments, downregulated its own natural receptor on these cells also after a preincubation of 1 hour. Furthermore, prolonged exposure of GM/SO cells to TNF-alpha for 5-7 days yielded a monocyte-macrophage-like morphology of some cells as these cells displayed an apparent glass and plastic adherence. In contrast, no such morphological changes could be observed in the presence of GM-CSF or SCF.

Cell Differentiation↗