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Biomedical subjects

A B Coleman

Publications and source records attributed to A B Coleman.

10 recordsLinked to original sources

Basic fibroblast growth factor sensitizes NIH 3T3 cells to apoptosis induced by cisplatin.

One mechanism by which chemotherapeutic agents kill tumor cells is by induction of apoptosis. Basic fibroblast growth factor (bFGF/FGF-2) has been reported to inhibit apoptosis in NIH 3T3 cells treated with chemotherapy drugs. We have investigated how bFGF modulates apoptosis induced by cisplatin in NIH 3T3 cells. Treatment with 10 microgram/ml cisplatin for 12 h induced apoptosis in 2 to 13% of the cells at 24 h post-treatment. Preincubation with 10 ng/ml bFGF for 24 h led to cisplatin-induced apoptosis in 20% to 50% of the cells. Preincubation with lower concentrations of bFGF (0.1-1 ng/ml) or simultaneous addition of bFGF and cisplatin had no effect on the amount of apoptosis. Pretreatment with bFGF also significantly decreased the dose-dependent survival of NIH 3T3 cells exposed to cisplatin, as determined by colony formation. Cells treated with 10 ng/ml bFGF showed a distinct morphology, appearing smaller and more refractile, before cisplatin exposure. The enhancement of cisplatin-induced apoptosis and the morphology shift demonstrated the same dose response to bFGF, and both effects were reversible if bFGF was removed from the medium for 24 h before cisplatin treatment. Mitogenic response to bFGF by NIH 3T3 cells saturated at 0.5 ng/ml, as measured by (3)H-thymidine uptake, and this response was blocked by coaddition of suramin, an inhibitor of FGF ligand-receptor interactions. Suramin did not reverse the enhancement of cisplatin-induced apoptosis by bFGF. Therefore, bFGF sensitized NIH 3T3 cells to cisplatin, and this effect might be mediated through a pathway separate from that used for mitogenic signaling.

3T3 Cells↗

Normal human melanocytes that express a bFGF transgene still require exogenous bFGF for growth in vitro.

The expression of basic fibroblast growth factor (bFGF) has been implicated as an important factor in the development of malignant melanoma. The timing of this expression suggests that bFGF plays a role early in melanoma tumor progression. Benign nevi produce bFGF, and cells cultured from these lesions show a loss of dependence on exogenous bFGF for growth. We have examined the effects of constitutive bFGF expression on the in vitro growth requirements of normal human melanocytes. bFGF was overexpressed in normal human epidermal melanocytes through genomic insertion of a human bFGF cDNA in a retroviral vector. These melanocytes produced the 18 kDa bFGF isoform as well as the higher molecular weight isoforms. The bFGF was not released into the culture medium, but it was present in the cell nucleus. The bFGF produced by these cells was mitogenic for 3T3 fibroblasts and therefore possessed functional activity; however, melanocytes producing bFGF had the same appearance and growth patterns as those infected with control virus or uninfected melanocytes. Expression of bFGF did not confer independence from the exogenous mitogen, nor would these cells form colonies in a soft-agar medium. These results indicate that expression of bFGF alone is not enough to cause aberrant growth of normal human melanocytes.

Cell Division↗

Mechanisms of human melanoma cell growth and tumor suppression by chromosome 6.

Breaks and deletions of chromosome 6 are among the most frequent karyotypic abnormalities that appear in human malignant melanoma cells, and chromosome transfer experiments have provided functional evidence for the presence of a melanoma tumor suppressor locus on chromosome 6[J.M. Trent et al., Science (Washington DC), 247: 568-571, 1990]. We have investigated the genetic mechanism of this suppression. We have found that the suppression of tumorigenicity that follows the introduction of a normal copy of chromosome 6 into the UACC 903 human melanoma cell line is correlated with increased chromosome 6 dosage, rather than with the presence of the transferred normal copy of the chromosome. Transfer of chromosome 6 into another human melanoma cell line, MelJuSo, does not result in suppression of primary tumor formation, although the additional copy of chromosome 6 does reduce the cell growth rate in vitro. Finally, we have identified a substantial portion of the chromosome that is evidently not involved in tumor suppression. We have observed that a copy of chromosome 6 derived from a normal cell but with a deletion involving chromosome bands 6q22-6q24 suppresses primary tumor formation in UACC 903 cells as effectively as the intact chromosome. We have thus provided additional information about the chromosomal location of this tumor suppressor and about its mode of action.

Animals↗

A prenatal and postpartum safety education program: influence on parental use of infant car restraints.

The effects of pre- and/or postnatal infant car safety education were examined. Educational approaches included demonstrations and talks on automobile crash statistics in the prenatal course; and a car safety film on the hospital television, a pamphlet given to each mother, and instructions to nurses to encourage parents' purchase and use of car restraints in the postpartum period. Although differences were not statistically significant, the reported and actual use of infant restraints on the trip home was highest in the pre- plus postnatal education group. Counseling in any period was associated with higher restraint use than on counseling. The pediatrician's role in effecting positive behavioral changes in this and other areas is emphasized.

Accident Prevention↗

Seat belt use and automobile safety counseling by pediatricians.

Safety restraints have proven effective in the prevention of serious automobile injuries and deaths, but safety education has been ineffective in getting consumers to use restraints. We surveyed the personal and counseling practices of a group of pediatricians over a one-year period to determine whether prenatal and postpartum safety education of parents influenced the pediatricians' own use of car restraints and their counseling practices. Seventy-two percent of participating pediatricians reported that they always or often wore restraints, but usage had not increased at the conclusion of the study. Seventy percent of pediatricians stated that they provided safety counseling in the prenatal and postpartum periods and during health examinations. There was a strong correlation between personal seat belt usage and frequency of counseling.

Accidents, Traffic↗