Search PubMed⌕ Search

Biomedical subjects

C Garbe

Publications and source records attributed to C Garbe.

203 records · Page 12Linked to original sources
PubMedDate not supplied

A fluorometric rapid microassay to identify anti-proliferative compounds for human melanoma cells in vitro.

A simple, rapid and reproducible assay for the determination of melanoma cell proliferation in vitro is described, based on the hydrolysis of a fluorogenic substrate by cell esterases in the cytoplasm of living cells. Human melanoma cells were cultured at several densities in 96-well culture plates for 24 h and were then incubated with 4-methylumbelliferyl heptanoate. The generated fluorescence showed a strong correlation with the cell numbers, similar to those assessed by determining the [3H]thymidine incorporation into cellular DNA and by quantifying the fluorescence obtained after DNA labelling with Hoechst 33258. The latter, however, was less sensitive and exhibited higher standard deviations. In addition, the method reliably detected the anti-proliferative effects of the anti-cancer compounds cisplatin and vindesine. It is, therefore, suggested that the fluorometric assay with 4-methylumbelliferyl heptanoate as substrate could prove useful for the screening of potential anti-cancer agents with anti-proliferative activity.

Antineoplastic Agents↗
PubMedDate not supplied

Epidemiology of cutaneous melanoma in Germany and worldwide.

Rising incidence rates of cutaneous melanoma have been observed during the last three decades. At the beginning of the 1970s 3 cases and in the 1990s 9 cases per 100,000 inhabitants and year were reported by the Saarland Cancer Registry in Germany. Other incidence studies from Germany in the 1990s even reported 10-12 cases per 100,000 inhabitants and year, which is more likely to be the representative melanoma incidence in Western Germany. In a worldwide comparison this is a medium incidence rate as compared to clearly higher incidence rates in the United States (10-20 cases per 100,000 inhabitants and year) and in Australia (40-60 cases per 100,000 inhabitants and year). In Europe the highest incidence rates have been reported from Scandinavia (about 15 cases per 100,000 inhabitants and year) and the lowest from the Mediterranean countries (about 5-7 cases per 100,000 inhabitants and year). Mortality rates likewise increased in Germany between 1970 and 1995 in males from 1.7 to 3.2 cases and in females from 1.6 to 2.0 cases per 100,000 inhabitants and year. In the 1990s, in Germany and in many other countries a leveling off of mortality rates was observed. 48,928 melanoma patients have been recorded by the Central Malignant Melanoma Registry from the German-speaking countries in the time period from 1983 to September 2000, and clinico-epidemiological analysis of cutaneous melanoma is based on this data material. While 2/3 of all melanoma patients in Germany were females in the 1970s, there is now a more balanced gender distribution with more than 45% of patients being males. Age distribution does not significantly change during the last three decades. Most melanomas are diagnosed in the age group between 50 and 60 years, 22% of all melanomas are diagnosed before the 40th year of age. A clear decrease of Breslow's tumor thickness was found from the beginning of the 1980s to the mid-1990s with the median thickness decreasing from 1.3 to 0.8 mm. Lower Breslow's tumor thickness at first diagnosis of cutaneous melanoma has only been reported from Australia. This development indicates improved early recognition of cutaneous melanoma which is presently the main factor for a more favorable prognosis.

Aging↗
PubMedDate not supplied

Prothymosin alpha augments deficient antitumor activity of monocytes from melanoma patients in vitro.

Human peripheral blood monocytes derived from normal donors, melanoma patients (MP) before and after chemotherapy (MPa) were assayed for their capacity to inhibit SK-MEL-28 melanoma cell growth in vitro; in addition, growth modulating effects by prothymosin alpha 1 (ProTa) were studied. After preincubation with or without ProTa for 1 day, monocytes were cultured in the absence or presence of interferon-gamma (rIFN-gamma) for a further day, and after cocultivation with SK-MEL-28 melanoma cells for 3 days monocyte/macrophage-mediated tumoristatic activity was determined employing the microculture tetrazolium (MTT) assay. The level of baseline growth inhibitory activity of unstimulated MP and MPa monocytes was 22% and 15%, respectively, and was significantly lower (p < 0.001) than that of normal monocytes (35%). The stimulation of monocytes/macrophages by rIFN-gamma greatly elevated the mean of their antitumor activity up to 44%, 49% and 58% in the group of MP, MPa and normal donors, respectively. ProTa significantly increased the level of monocyte-mediated growth inhibition of MP and normal donors, when it was applied alone or in combination with rIFN-gamma. Monocytes of MP at early stages (I and II) of their disease, when incubated with rIFN-gamma, showed a higher increase in tumoristatic activity than at stage III and tended to be the most susceptible to preincubation with ProTa followed by rIFN-gamma activation. However, on average tumoristatic activity of MP/MPa monocytes was significantly lower compared with that of normal monocytes, when activated with rIFN-gamma or ProTa alone or combined. Moreover, no effects on TNF-alpha secretion of MP/MPa monocytes were found by ProTa and/or rIFN-gamma, whereas TNF-alpha levels from normal monocytes were significantly increased by the two stimuli. These results indicate that monocyte disorders in melanoma patients may be partially normalized by ProTa.

Adult↗
PubMedDate not supplied

Paracrine and autocrine regulation of human melanocyte and melanoma cell growth by transforming growth factor beta in vitro.

It has been considered that the growth of human melanoma cells is positively and negatively regulated by transforming growth factors. To investigate further the role of transforming growth factor beta (TGF-beta) in melanoma biology, we analysed paracrine and autocrine growth regulatory properties of TGF-beta in normal human melanocytes and malignant melanoma cell lines in vitro. Exogenously added TGF-beta 1 potently inhibited normal melanocyte proliferation and DNA-synthesis in all cultures examined; in contrast, TGF-beta 1 inhibited only moderately or not at all the growth of cultured melanoma cells. Melanoma cell lines established from metastatic lesions were found to be less sensitive to TGF-beta 1 than those derived from primary melanomas. TGF-beta 1 resistance correlated with high levels of active TGF-beta secreted by metastatic cell lines. Inactivation of endogenously produced TGF-beta by neutralizing anti-TGF-beta antibody resulted in the stimulation of cell proliferation of a TGF-beta-sensitive primary melanoma cell line but not of a resistant metastatic one. These findings suggest that TGF-beta may function as a paracrine and autocrine growth inhibiting factor in the growth regulation of human melanocytic cells. The gradual loss of response of melanocytic cells to TGF-beta during malignant progression suggests that escape of melanoma cells from growth regulation by TGF-beta could be involved in melanoma oncogenesis.

Antibodies↗