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M Roser

Publications and source records attributed to M Roser.

27 records · Page 2Linked to original sources

Studies on cultured fibroblasts from patients with cutaneous malignant melanoma.

Cultured fibroblasts from patients with cutaneous malignant melanoma (CMM) were tested for chromosomal instability by determination of micronuclei (MN) and sister chromatide exchange (SCE). The constitutive as well as the UV-induced level of MN was increased in CMM patients, being most pronounced in the familial cases. There was an increased UV sensitivity in CMM by using SCE, but no spontaneously enhanced SCE value. The enhanced UV sensitivity in CMM patients was in a comparable range as those of XP heterozygotes. We thus conclude that chromosomal instability is a concurrent feature of a genetic predisposition for CMM.

Cells, Cultured↗

Increased UV-induced sister-chromatid exchange in cultured fibroblasts of first-degree relatives of melanoma patients.

Cultured fibroblasts of 17 first-degree relatives of familial melanoma patients and six first-degree relatives of cutaneous melanoma (CMM) patients with multiple CMM primaries were tested for in vitro sensitivity to UV light. Fibroblasts of nine familial CMM patients with a known UV-sensitivity and 19 healthy probands served as a control. Sister chromatid exchange (SCE) was used as a parameter to detect UV-induced genotoxic damage. We found significantly (p less than 0.001) increased UV-induced SCE levels in familial melanoma patients, as well as in first-degree relatives of familial melanoma patients (p less than 0.001) after UV-A,B irradiation (375 J/m2), compared to the healthy probands without a family history of CMM. A significant (p less than 0.001) increase of UV-induced SCE was also observed in the relatives of CMM patients with multiple CMM primaries. In addition, the spontaneous SCE were significantly increased (p less than 0.05) in familial CMM patients. This study shows that increased UV sensitivity is a familial phenomenon. It is consistent with the concept of a genetic predisposition to CMM, which is based on increased UV sensitivity and may help to define groups with an elevated risk of developing cutaneous malignant melanoma.

Cells, Cultured↗

Elevated frequencies of micronuclei in cultured fibroblasts after freezing and thawing.

Spontaneous micronuclei (MN) were determined in 69 fibroblast lines in the first subculture after cryoconservation. 45 cultures (65%) showed micronuclei in the normal range (less than 10 MN/500 cells), but 24 (35%) exhibited an elevation up to 60 MN/500 cells. In order to determine whether freezing and thawing is responsible for the enhanced MN level we studied the persistence of elevated MN in 10 cell cultures after freezing and thawing, and found that the MN levels returned to normal after 3 subcultures. In addition, the micronucleus formation before and after freezing was investigated in 2 newly established cell cultures obtained from probands whose cells had a particularly high number of MN. Both cultures had regular MN levels before freezing but a more than doubled number of MN when frozen samples were recultivated. This effect of the freezing procedure was confirmed with 5 separate biopsies obtained from the same donor. Since a freezing-related increase in MN was constantly observed in cells from some individuals but not in others, it might be possible that it is a constitutive trait which causes cultured fibroblasts of some individuals to be hypersensitive to the freezing and thawing procedure. It is also noteworthy that fibroblasts from 8 out of 12 probands with a familial malignant melanoma exhibited this phenomenon.

Biopsy↗

Increased numbers of spontaneous micronuclei in blood lymphocytes and cultures fibroblasts of individuals with familial cutaneous malignant melanoma.

In vitro detection of micronuclei was used to determine spontaneous chromosomal instability in cultured fibroblasts of 28 healthy normal controls, 28 individuals with nonfamilial cutaneous malignant melanoma (CMM) and 14 people with familial occurrence of CMM. Lymphocytes from 40 healthy controls, 40 CMM patients and 6 individuals with familial CMM were also compared for spontaneous expression of micronuclei in vitro. In the familial cases micronucleus frequency was found to be higher, both in cultured fibroblasts (P less than 0.005) and in lymphocytes (P less than 0.001) as compared to normal controls. There was no significant difference between nonfamilial cases and normal controls. We conclude that chromosomal instability may contribute to a genetic risk for development of cutaneous malignant melanoma.

Adult↗

Ultraviolet-induced chromosomal instability in cultured fibroblasts of heterozygote carriers for xeroderma pigmentosum.

Fibroblast cultures of seven patients with xeroderma pigmentosum (XP), 19 healthy sibs or parents of XP patients (XP-heterozygotes), and 24 healthy normal controls were studied for chromosome instability induced by ultraviolet rays (UV). We used a UV source that contained predominantly UV-A and UV-B at an intensity of 500 J/m2 and evaluated the induction of micronuclei (MN) and sister chromatid exchange (SCE). the XP homozygotes had a UV sensitivity that was clearly above that of all heterozygotes and normal controls. Heterozygotes had an increased rate of UV-induced MN (4.76 +/- 1.96 vs. 1.82 +/- 2.05, p less than 0.0001) and increased UV induction of SCE (13.21 +/- 3.49 vs. 9.01 +/- 1.25, p less than 0.001), as compared to normal controls. These data support epidemiologic findings that suggest that XP heterozygotes are particularly cancer prone. In addition, the determination of the UV sensitivity in vitro as described may be used for genetic counseling of asymptomatic relatives of XP patients.

Cells, Cultured↗

Ultraviolet-induced formation of micronuclei and sister chromatid exchange in cultured fibroblasts of patients with cutaneous malignant melanoma.

Genetically enhanced sensitivity to ultraviolet (UV) radiation may play an important role in the development of cutaneous malignant melanoma (CMM). This was studied in cultured fibroblasts of 26 CMM patients and controls by micronucleus (MN) test and sister chromatid exchange (SCE) after UV irradiation (375 J/m2). Sister chromatid exchange and MN formation were used as parameters to detect the UV-induced genotoxic damage in the individual cell strains. We found that the UV-induced level of MN was significantly increased in CMM patients (p = 0.0005), being most pronounced in the familial cases (p = 0.0001). Ultraviolet-induced SCE was also elevated in CMM patients (p = 0.001), but there was no difference between familial and nonfamilial cases. The present findings indicate that genetic predisposition contributes to the development of CMM in a subset of CMM patients and may be due to an enhanced susceptibility to UV light.

Adult↗

[Clinical recognition of early forms of malignant melanoma].

The clinical diagnosis of malignant melanoma (MM) is based on the subjective evaluation of objective measurable parameters (criteria). The accuracy of melanoma diagnosis by dermatologists is only 75%. Particularly difficult is the diagnosis of precursors or early stages of MM. Therefore, we have studied on the one hand the intra- and interindividual reproducibility of the clinical diagnosis of pigmented lesions, and on the other hand the clinico-histopathological correlation. In addition, we have conducted a preliminary investigation designed to evaluate whether image analysis (objective and reproducible) could be used as an auxiliary instrument to differentiate between benign and malignant melanocytic lesions. In the clinical study, the intraindividual reproducibility of the combination of criteria was 69%. The interindividual reproducibility of single criteria even exhibited a range of up to 36%. Histologically "atypical/dysplastic" melanocytic lesions were considered to require excision as frequently as histologically regular melanocytic lesions. Using image analysis (single threshold segmentation, standard deviation of intensity distribution, ratio of area to circumference, Fourier analysis), we could show that it may be possible to differentiate between benign and malignant melanocytic lesions. Therefore, image analysis may be very helpful in determining the dignity of melanocytic lesions.

Adult↗

[Chromosome instability in patients with malignant melanoma of the skin].

The certainty of a strong genetic predisposition to malignant melanoma was first established over 35 years ago. Since it has been shown that constitutive chromosomal instability is significantly correlated with the familial occurrence of cancer, we have studied spontaneous micronucleus rates in fibroblast cultures from 44 melanoma patients, 44 healthy probands and 78 patients with bronchial carcinoma. Here we report a significantly (p = less than 0.0005) increased spontaneous chromosomal instability in patients with cutaneous malignant melanoma compared to healthy controls and other tumor patients (bronchial carcinoma).

Adolescent↗