BACKGROUND: The incidence of and mortality from melanoma are increasing and no effective treatment for disseminated disease exists. Studies of factors influencing participation in prevention and early detection of melanoma are therefore warranted. In the present study, participants in public melanoma screening were compared with a sample of the Swedish population with respect to concern for nevi, perceived risk for melanoma, knowledge about melanoma, and sources of information. Gender differences were studied. METHOD: Consecutive participants in public melanoma screening (Participants) received questionnaires at registration for skin examination; 235 (96%) responded. Questionnaires were distributed by mail to a random sample of the Swedish population (Public); 1,070 (63%) responded. RESULTS: Participants were more concerned about nevi, and a higher proportion had previously consulted physicians for suspected lesions compared with the Public. Participants were better informed in terms of the number of sources of information and knowledge of melanoma and risk factors. There were no differences regarding perceived risk and there was a mixed picture concerning knowledge of sun effects and sun protection. Gender differences were found for perceived susceptibility to, knowledge of, and number of sources of information about melanoma, favoring women. CONCLUSION: The preventive aspects of screening as well as the good prognosis of melanoma detected early should be stressed in invitations to skin cancer screening. New approaches for reaching men are warranted.

Adolescent↗

PubMedDate not supplied

Increasing incidence rates of squamous cell carcinoma of the skin in Sweden.

The incidence of squamous cell carcinoma of the skin is increasing world-wide, and in Sweden this tumour is one of the most rapidly increasing malignancies. The aim of this study was to investigate incidence trends of squamous cell carcinoma in Sweden. For the 39,805 tumours registered in the Swedish Cancer Registry 1961-1995, incidence rates were calculated according to gender, age, anatomical site and unit surface area. Multivariate analysis was performed with the age-period-cohort model. Age-standardized incidence rates increased substantially in both men (+425%) and women (+146%) during this period. The highest rates per unit surface area were seen for chronically sun-exposed head-neck sites. Age-specific incidence rates increased in ages > or =60 years during the study period. Multivariate analyses showed that age, period and cohort effects in men could best explain the incidence rates, while in women the age-period effects model was adequate. In conclusion, a rapidly increasing incidence trend for squamous cell carcinoma was found, probably explained by increased accumulated sun exposure and increasing incidence among the elderly.

Adolescent↗

PubMedDate not supplied

Uptake of [131I]thiouracil in tumours of patients with disseminated malignant melanoma. A pilot study.

Previous studies on mice carrying melanoma have shown that 5-iodo-2-thiouracil (ITU) is accumulated in the tumours due to its specific incorporation into melanin during its synthesis. ITU is also selectively localized in murine melanoma metastases and in cultured human melanoma cells. Progressive formation of melanin is, however, a prerequisite for the incorporation. Four patients with disseminated melanoma were injected intravenously with 39-62 MBq [131I]TU. Blood and urine samples were gradually collected, and 3-7 days postinjection tumours were biopsied and examined by impulse counting. The patients were scanned with a gamma camera over the total body daily for 3-4 days. The radioactivity was rapidly excreted. Poor melanin pigmentation of the tumours and low proliferation rate (possibly induced by chemotherapy) decreased the uptake of radioactivity by the tumors, and no imaging was possible. One of the patients, however, had clearly progressive disease with darkly pigmented metastases which contained considerably higher levels of radioactivity than the surrounding skin. Calculations indicated that a doubling of the radioiodine dose would probably make visualization of the tumours possible.

Bone Neoplasms↗

PubMedDate not supplied

Radiation therapy in early glottic cancer. Analysis of 177 consecutive cases.

Early vocal cord carcinomas (TiS or T1) in a consecutive series of 177 patients treated by primary radiotherapy over a 10-year period 1970-79 at the Department of General Oncology, Radiumhemmet, Karolinska Sjukhuset, were analysed regarding treatment results. In 137 cases the tumours were invasive (T1N0M0) and in 40 cases carcinoma of in situ type (TiS). Patient were treated with cobalt 60 gamma irradiation in fractions of 2 Gy up to a total dose of 64 Gy delivered as split course (CRE=17.8). Minimum follow-up time was 5 years. Tumour recurred in 21 cases (12%). All but 4 patients were rescued by subsequent surgery, giving 98% total survival. Treatment failures after primary radiotherapy were analysed in detail. Failures could not be attributed to treatment irregularities. No difference in pretreatment tumour size was detected when cured patients were compared with patients who relapsed. Biological factors that cause a relative radioresistance are considered to be the main reason for radiotherapy failures in early glottic cancer.

Carcinoma↗

PubMedDate not supplied

Cytotoxicity and DNA cross-linking induced by peptide conjugated m-L-sarcolysin in human melanoma cells.

Peptichemio is a complex of six peptides containing m-L-sarcolysin which is used in cancer chemotherapy. One of the peptides, L-propyl-m-sarcolysyl-L-p-fluorophenylalanine (PSF), is highly toxic to melanoma cells. We have compared the effects of melphalan, m-L-sarcolysin and PSF on human melanoma cell lines. PSF was 35-fold and 28-fold more toxic to RPMI 8322 melanoma cells than melphalan and m-L-sarcolysin, respectively. Similar differences in the cytotoxic effects of PSF and m-L-sarcolysin were also seen with two other melanoma cell lines. The cytotoxicity of both PSF and m-L-sarcolysin to RPMI 8322 melanoma cells was potentiated by depletion of cellular glutathione. Both PSF and m-L-sarcolysin caused a protracted induction of DNA cross-links in RPMI 8322 cells, with maximum at 24 hours after drug exposure. PSF induced 9-fold higher levels of DNA interstrand cross-links than m-L-sarcolysin, indicating that the increased cytotoxicity of this drug is associated with a more efficient induction of DNA damage.

DNA, Neoplasm↗

PubMedDate not supplied

Increased toxicity and DNA cross-linking by peptide bound m-L-sarcolysin (Peptichemio) as compared to melphalan and m-L-sarcolysin in human melanoma cell lines.

Alteration of the melphalan molecule by shifting the di(2-choroethyl)aminogroup from the para- to the meta-position of the phenylalanine residue results in m-L-sarcolysin. By covalent conjugation of different amino acids at the amino- and carboxylgroups of this molecule, a mixture of six peptides known as Peptichemio has been synthesized. In a previous investigation we found that Peptichemio was less toxic to human lymphoblasts than m-L-sarcolysin. In contrast, in the present investigation we found that Peptichemio has higher cytotoxic effect than m-L-sarcolysin on two human melanoma cell lines. The higher cytotoxicity was paralleled by a higher induction of DNA cross-links by Peptichemio as compared to m-L-sarcolysin. A comparative analysis of the six peptides on Peptichemio showed differences in cytotoxic effects on a melanoma cell line. One of the six peptides displayed a considerably higher cytotoxicity than peptichemio itself.

Cell Line↗

PubMedDate not supplied

Effect of combined treatment with cisplatin and 5-fluorouracil on cell growth and cell cycle kinetics of a mouse ascites tumor growing in vivo.

The effect on cell growth and cell cycle kinetics of 0.8 mg cisplatin (CDDP)/kg body weight and 36 mg 5-fluorouracil (5-FU)/kg body weight given separately and in combination was studied on Bp8 mouse ascites sarcoma growing in vivo. Cell growth inhibition after combined treatment was delayed 12 hours but was persistent, while the cell growth inhibition was immediate after single drug treatment with a relative cell regrowth observed at the end of the observation period. The prolonged cell growth inhibition after combined treatment was probably due to cell death. Some cell kinetic interactions were found after combined treatment. An increased flow of cells from G1 was observed during the whole observation period. The depressed outflow of cells from S after single drug treatment was abolished during the first 24 hours following combined treatment. No prolongation was found on the CDDP-induced G2 delay. An increased relative number of cells in G2 following combined treatment was, however, found at 72 hours. This was due to an increased flow of cells from S to G2 seen after 48 hours. The molecular reasons and consequences are discussed.

Animals↗

PubMedDate not supplied

Melphalan-induced DNA cross-linking and inhibition of DNA and RNA synthesis in human melanoma and lymphoblast cells.

Melphalan inhibits the incorporation of 3H-thymidine and 3H-uridine significantly more in phytohaemagglutinin (PHA)-stimulated human lymphocytes than in a human melanoma cell line (RPMI 8322). Melphalan - induced total DNA cross-linking was 1.7 times higher and DNA interstrand cross-linking was 1.8 times higher in the PHA-stimulated lymphocytes than in the melanoma cells. A higher level of DNA cross-linking was required in melanoma cells than in PHA-stimulated lymphocytes to obtain similar levels of inhibition of incorporation of 3H-thymidine and 3H-uridine. The outflow of cells from G1 to S phase was significantly more inhibited by melphalan in the lymphocytes than in the melanoma cells. Thus the melanoma cells can replicate and transcribe DNA in the presence of levels of DNA damage, which in PHA-stimulated lymphocytes strongly inhibit DNA and RNA synthesis.

DNA Damage↗

PubMedDate not supplied

Allele losses in malignant melanoma reflect random events.

The genetic basis for cutaneous malignant melanoma is indicated by the observations of inherited disease and the apparent correlation between exposure to mutagenic UV-light and an increased incidence of the disease. We have focused on the hypothesis that advanced disease results from gene deletions on specific chromosomes. Therefore loss of heterozygosity for polymorphic loci on all human chromosomes in a set of eleven metastases of cutaneous malignant melanomas was studied. Allele losses were detected on several chromosomes in a scattered pattern, indicating that the mechanisms of initiation and progression in these do not involve gross chromosomal deletions.

Alleles↗

PubMedDate not supplied

Effect of cis-diammino-dichloro-platinum (II) on cell growth and cell cycle progression of a mouse ascites tumor growing in vivo.

Cell kinetic studies of cis-platin (CDDP) have been few with divergent results. In this study, the effect of 12.5 and 25 micrograms CDDP/animal corresponding to approximately 0.4 and 0.8 mg CDDP/kg body weight was described when treating the Bp8 ascites sarcoma growing in mice. From sequential studies of the total number of cells together with the composition of cells in the cell cycle, the flow of cells through the cell cycle was calculated. A dose-dependent cell growth inhibition was found with almost immediate effect following the higher dose, while an inhibitory effect on cell growth with the lower dose was delayed 24 hours. The cell flow from the various phases of the cell cycle for the first 24.48 hours following administration of the lower dose, was increased from the G1-phase and mitosis, with normal flow from the S-phase and depressed outflow from the G2-phase. Thereafter the flow rates from all cell cycle phases were decreased. For the higher dose, the outflow rates from all phases of the cell cycle were depressed up to 72 hours. The maximum platination of DNA was found one hour after treatment. The results indicate that the mechanisms responsible for the passage through the G2 stage of the cell cycle are more sensitive to the treatment of CDDP than replicative DNA synthesis. This experimental system may be used as a basis for further mechanistic studies of the antitumor effect of anticancer drugs.

Animals↗

PubMedDate not supplied

Melphalan-induced DNA cross-linking in human melanoma cells and phytohaemagglutinin-stimulated lymphocytes in relation to intracellular drug content and cellular levels of glutathione.

Melphalan-induced DNA cross-linking was compared in a human melanoma cell line (RPMI 8322) and in phytohaemagglutinin (PHA)-stimulated lymphocytes. In both cell types a delayed induction of DNA cross-links was observed, with maximum DNA cross-linking occurring 6-12 hours after drug exposure. Significantly higher peak levels of DNA cross-links were found in PHA-stimulated lymphocytes, total DNA cross-linking being 2.5 times and DNA interstrand cross-linking 2.2 times higher. The intracellular content of free melphalan was 1.3-fold higher in RPMI 8322 cells, thus the lower DNA cross-linking was not due to a lower drug concentration in these cells. RPMI 8322 cells had a 1.8-fold higher level of glutathione, possibly indicating a higher capacity of these cells to inactivate melphalan.

Cell Line↗

PubMedDate not supplied

Different melphalan toxicity and DNA cross-linking in human melanoma cells as compared to phytohaemagglutinin-stimulated lymphocytes.

The cytotoxic effect of melphalan, measured as drug induced inhibition of cellular 3H-thymidine incorporation, was lower in RPMI 8322 melanoma cells than in phytohaemagglutinin-stimulated lymphocytes. Melphalan induced a 1.8-fold higher level of total cross-linking and a 1.5-fold higher level of DNA interstrand cross-linking in the phytohaemagglutinin-stimulated lymphocytes compared to the RPMI 8322 melanoma cells. In addition, higher levels of cross-linking were found in the newly synthesized DNA of lymphocytes in S-phase, as compared to S-phase RPMI 8322 cells. The cellular incorporation of 3H-melphalan was about four times higher in RPMI 8322 cells than in phytohaemagglutinin-stimulated lymphocytes. Thus, the lower toxicity of melphalan in RPMI 8322 cells and the lower levels of melphalan induced DNA cross-linking in these cells is due to intracellular factors rather than a lower cellular uptake of melphalan.

Cell Line↗

PubMedDate not supplied

Prognostic value of serum analyses of S-100 protein beta in malignant melanoma.

In the present study serum levels of S-100 protein beta were measured in 643 patients with cutaneous malignant melanoma. An immuno-radiometric assay with three monoclonal antibodies against bovine S-100 protein beta subunit was used. At the time of blood sampling 553 patients were in clinical stage 1, 24 in clinical stage II and 66 in clinical stage III. The overall survival rate was strongly associated with serum levels of S-100 protein. The observed/expected death ratio was markedly increased with increasing levels of S-100 beta (p < < 0.001). Our data strongly suggest that S-100 beta in serum is an independent prognostic marker and may be useful in identifying high-risk cases and monitoring response to therapy in patients with malignant melanoma.

Animals↗