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Biomedical subjects

L E Gerweck

Publications and source records attributed to L E Gerweck.

63 records · Page 4Linked to original sources
PubMed1977

Radiation sensitivity of cultured human glioblastoma cells.

Glial cells from 2 normal brains and 9 astrocytomas were cultured in vitro. The most rapidly proliferating cell lines were obtained from Grades III-IV astrocytomas. Normal glia proliferated slowly and growth ceased after 20 to 40 generations. The response of 3 Grade III-IV lines to graded doses of radiation was determined by colony formation and end point dilution technique. Two of the 3 lines were relatively radioresistant compared to other human cell lines; this may partially account for the radiation resistance of high grade astrocytoma tumors.

Brain Neoplasms↗
PubMedDate not supplied

Effect of basic fibroblast growth factor on angiogenesis and growth of isografted bone: quantitative in vitro-in vivo analysis in mice.

Basic fibroblast growth factor (bFGF), a constituent of bone and cartilage matrix, has been shown to be a potent mitogen for osteoblasts and chondrocytes and yet an inhibitor of chondrocyte terminal differentiation in cell culture. To characterize the effect of bFGF on bone formation, whole neonatal murine femora were cultured in the presence or absence of bFGF and a neutralizing antibody against bFGF. In vitro, femoral elongation was provided by cartilage growth only; the calcified diaphyseal zone stained by oxytetracycline did not increase. When bFGF was added to the culture medium, longitudinal growth of the proximal and distal cartilage was inhibited in a dose-dependent manner (p < 0.05), and the number of hypertrophic chondrocytes in the growth plate was reduced. This phenomenon was absent in the presence of a neutralizing antibody, which when given alone significantly promoted femoral elongation. In contrast, in vivo after transplantation into adult mice bearing dorsal skin fold chambers, femora rapidly calcified after revascularization. This observation supports the notion that bone formation largely depends on angiogenesis-mediated events. To verify this hypothesis, angiogenesis and bone formation were quantified using bFGF known to be a stimulator of angiogenesis. Calcification of grafted femora was accelerated by bFGF given intraperitoneally. The neutralizing antibody slightly suppressed angiogenesis and femoral elongation (not statistically significant), whereas intravenous injections of both substances did not reveal a significant modulatory effect. In vivo the effect of systemically administered bFGF was inhomogeneous, but there was a strong correlation between angiogenesis and endochondral calcification (p < 0.001). These results suggest that exogenous bFGF modulates bone formation in vitro by inhibition of terminal differentiation of chondrocytes in the growth plate, and angiogenesis and concomitant in vivo events are pivotal in the promotion of rapid bone formation.

Animals↗
PubMedDate not supplied

The cytotoxic effect of cis-diamminedichloroplatinum(II) on cultured Chinese hamster ovary cells at elevated temperatures: Arrhenius plot analysis.

The effect of cis-diamminedichroloplatinum (II) (cis-DDP) and hyperthermia on cultured Chinese hamster ovary (CHO) cells were investigated. Cells were treated with 6 microM cis-DDP for various durations of time at temperatures ranging from 37 to 43 degrees C, and cell survival curves were determined as a function of treatment time. The cytotoxic effect of cis-DDP increased with increasing temperatures, indicating that hyperthermia enhanced cytotoxicity of cis-DDP. Arrhenius analysis of surviving fraction data (6 microM cis-DDP) yielded activation energies of 61 kcal/M between 37 and 41 degrees C and 213 kcal/M between 41 and 43 degrees C. Further experiments using two different drug concentrations (3 and 12 microM) confirmed these activation energies in these two different temperature ranges. However, the activation energy for 12 microM cis-DDP given in the temperature range 33-37 degrees C was 22 kcal/M, which is smaller than those found above 37 degrees C. This activation energy appeared to be identical to that reported for the degradation or depurination of DNA. The activation energy between 37 and 41 degrees C, i.e. approximately 61 kcal/M, was twice as great as that found for alkylation of thio-TEPA, an alkylating agent. This may indicate that the mechanism of action of cis-DDP differs from that of thio-TEPA. A greater activation energy observed in the range of 41-43 degrees C is most likely attributable to the additive effect of hyperthermia and thermal enhancement for cis-DDP. Although only one data point is available at the temperature above 43 degrees C, it suggests that the activation energy is identical to that for hyperthermia alone.

Animals↗
PubMedDate not supplied

The effect of androgen deprivation and radiation therapy on an androgen-sensitive murine tumor: an in vitro and in vivo study.

PURPOSE: The purpose of this research was to assess whether or not tumor eradication by irradiation can be enhanced by prior androgen deprivation in an androgen-dependent rodent tumor model. MATERIALS AND METHODS: The androgen-sensitive Shionogi SC-115 mouse mammary carcinoma was grown in athymic male NCr/Sed (nu/nu) mice and in culture. An androgen-deprived environment was created in vivo by surgical orchiectomy and in vitro through the use of charcoal-stripped androgen-free medium. The dose of radiation required to control 50% of tumors (tumor control dose [TCD50] assay) was used to assess the radiation response of tumors grown in vivo. Colony-formation assays were used for in vitro assessment. RESULTS: After orchiectomy, Shionogi tumors regress in volume quickly but inevitably regrow as androgen-insensitive clones. The TCD50 for 6-mm Shionogi tumors grown in intact mice was 89.0 Gy (95% confidence intervals [CI]: 83.4 to 94.9). When orchiectomy was performed 24 to 48 hours prior to irradiation, the TCD50 fell to 60.3 Gy (95% CI: 54.8 to 66.3). When irradiation was withheld until maximum tumor regression following orchiectomy, it was lower still-42.1 Gy (95% CI: 37.4 to 47.4). In vitro studies demonstrated no profound changes in intrinsic radiation sensitivity induced by prior androgen deprivation, although there was a trend toward lower Dzero values with increasing duration of deprivation. DISCUSSION: Prior androgen deprivation enhances the ability of irradiation to eradicate Shionogi tumors in vivo. It is likely that this effect results from cytoreduction and/or improvement in the nutritional status of a smaller tumor, but changes in intrinsic radiation sensitivity cannot be excluded.

Androgens↗