[Ultraviolet rays can cause skin cancer. Cumulative effect of physical and biological factors].
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Basal Cell Carcinoma↗
Biomedical subjects
U Ringborg
Publications and source records attributed to U Ringborg.
[The Open House campaign for skin examinations resulted in valuable experiences].
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Evaluation Studies as Topic↗
Psychological effects of participation in a prevention programme for individuals with increased risk for malignant melanoma.
The Swedish Melanoma Study Group runs a programme aimed at prevention and early detection of premalignant and malignant melanoma in families with two or more members having malignant melanoma. Psychological consequences of participation in this programme were studied. A questionnaire containing items concerning cognitive and emotional responses to the programme was completed by 115 consecutive individuals at their first visit to the clinic. The same questionnaire was administered by mail 7 months later. The levels of psychological and psychosomatic problems were relatively low at both points of assessment. No negative psychological effects were found, neither in the group with dysplastic naevus syndrome (DNS) with increased risk for malignant melanoma, nor in the group without dysplastic naevi. Only one variable, "emotional responses to the visit" differentiated between the groups, with higher scores in the group without DNS. A majority of the individuals expressed positive attitudes to the clinic.
Adult↗
[Unexpected telephone call informed about malignant melanoma].
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Adult↗
Sensitization of human melanoma cells to the cytotoxic effect of melphalan by the glutathione transferase inhibitor ethacrynic acid.
Glutathione transferases are enzymes implied in the resistance of tumor cells to bifunctional alkylating cytostatic drugs. We have investigated the effect of the glutathione transferase inhibitor by ethacrynic acid on the cytotoxicity of melphalan to a human melanoma cell line (RPMI 8322) with a high level of glutathione transferase activity. Using 1-chloro-2,4-dinitrobenzene as substrate, ethacrynic acid was shown to inhibit the activity of purified human glutathione transferases, with 50% inhibition values of 1, 10, and 15 microM for transferase mu (class mu), transferase epsilon (class alpha) and transferase pi (class pi), respectively, all of which occur in RPMI 8322 cells. Ethacrynic acid at a concentration of 20 microM, which by itself was noncytotoxic, increased the cytotoxicity of melphalan to RPMI 8322 human melanoma cells approximately 2-fold. The induction of DNA interstrand cross-links by 40 microM melphalan was increased 1.4-fold by 30 microM ethacrynic acid. These results indicate that a potentiation of the cytotoxic effect of bifunctional alkylating agents can be achieved by inhibition of glutathione transferase and that the enhanced cytotoxicity may be caused at least in part by increased formation of drug-DNA adducts.
Cell Survival↗
Early detection and prevention of cutaneous malignant melanoma: emphasis on Swedish activities.
The incidence of cutaneous malignant melanoma has increased more than the incidence of any other malignant tumour disease in Sweden the last three decades. Parallel to the almost 6% annual increase in incidence there has been a 3% annual increase in mortality. The knowledge of significant risk factors for melanoma (intermittent sun exposure and phenotypic traits related to skin pigmentation and propensity for dysplastic nevi) as well as the relationship between thin tumours and a good prognosis has been used to develop strategies for primary and secondary prevention. In this paper the Swedish programs for education of physicians, nurses and the general population are presented. A nationwide program for the identification and follow-up of individuals with dysplastic nevus syndrome has been initiated. The effects of the programs are followed by population-based melanoma registries.
Humans↗
Comparative study of two human melanoma cell lines with different sensitivities to mustine and cisplatin.
The cytotoxic effects of the bifunctional DNA-reactive drugs cisplatin, mustine and melphalan were studied in two human melanoma cell lines, RPMI 8322 and A 375. A 375 cells were 3.0 times more sensitive to cisplatin and 1.5 times more sensitive to mustine than RPMI 8322 cells. In contrast, A 375 cells were less sensitive to melphalan than RPMI 8322 cells. The increased sensitivity of A 375 cells was parallelled by an increased induction of DNA interstrand crosslinks following exposure to cisplatin and mustine. After cisplatin exposure A 375 cells also showed higher levels of platinum-DNA intrastrand adducts than RPMI 8322 cells. The increased effect of cisplatin in A 375 cells was not due to an increased drug accumulation in these cells. The higher sensitivity of A 375 cells to cisplatin may be related to lower intranuclear levels of glutathione, compared to RPMI 8322 cell nuclei, while the sensitivity to mustine may depend on lower overall levels of glutathione than in RPMI 8322 cells.
Cell Line↗
Carmustine-induced toxicity, DNA crosslinking and O6-methylguanine-DNA methyltransferase activity in two human lung cancer cell lines.
O6-methylguanine-DNA methyltransferase (O6-MT) probably plays an important role in the repair of chloroethylnitrosourea-induced DNA damage. O6-MT was studied as a possible drug resistance factor in two human lung cancer cell lines, one small cell lung cancer (U1690) and one non-small cell lung cancer (U1810), with different sensitivities to carmustine. The U1810 cell line was 3.4-fold more resistant to carmustine than U1690 cells, although the two cell lines were equally sensitive to mustine, melphalan and cisplatin. A 23-fold higher level of DNA interstrand crosslinks was observed following exposure of U1690 cells to carmustine compared with U1810 cells. The O6-MT activity of U1810 cells was 11 times higher than that of U1690 cells. The O6-MT activity in the U1810 cells showed a dose-dependent decrease after exposure to carmustine. These results show a correlation between increased O6-MT activity, decreased drug induced DNA interstrand crosslinking and cellular resistance to carmustine.
Carcinoma, Non-Small-Cell Lung↗
Induction and time course of DNA single-strand breaks in lymphocytes from patients treated with dacarbazine.
Dacarbazine (DTIC) is an antitumor agent, used for the treatment of metastatic melanoma. It is metabolized to an alkylating agent which reacts with DNA. A fast and simple method was developed in order to measure drug-induced DNA damage in lymphocytes isolated from frozen blood samples of treated patients. The level of DNA damage was determined as single-strand breaks (SSB) by means of the alkaline elution technique using the fluorochrome Hoechst 33258. DTIC induced SSBs in lymphocytes. Most of the DNA damage was repaired after 20 h but after subsequent daily treatments there was an accumulation of SSB. The method described here can be used for monitoring DNA damage in lymphocytes of persons exposed to genotoxic compounds.
DNA Damage↗
Regional hyperthermic perfusion with melphalan after surgery for recurrent malignant melanoma of the extremities. Swedish Melanoma Study Group.
A prospective randomized trial testing regional hyperthermic perfusion with melphalan has been conducted. Sixty-nine patients with recurrent malignant melanoma of the extremities were randomly allocated to surgery (36 patients) or surgery plus regional perfusion (33 patients). Prognostic variables concerning primary tumor as well as the recurrent disease were evenly distributed in the groups, excluding any bias in the randomization. Median tumor-free survival after randomization was 17 months in the perfusion group and 10 months in the control group. There were 15 locoregional recurrences in the perfusion group and 24 in the control group. The tumor-free survival curve was significantly (P = .044) better for the perfusion group than for the control group. Median survival time after randomization was 57 months in the perfusion group and 35 months in the control group. This difference was not significant. One patient died within 1 month after perfusion of pulmonary embolism. Regional hyperthermic perfusion after surgery of recurrent malignant melanoma should only be recommended in prospective and controlled trials, until its value has been proven in several randomized studies.
Adult↗
Adjuvant chemotherapy. A discussion of some basic principles.
Some basic principles of adjuvant chemotherapy are discussed as mode of action, molecular mechanisms, drug resistance, patient selection, and early and late toxicity. It is assumed that in the future improved methods for selecting patients will increase the possibilities to cure patients with micrometastases of solid tumors by adjuvant chemotherapy.
Antineoplastic Agents↗
[Identification of resistance factors is a step towards optimized treatment with cytostatic agents].
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Animals↗
Trends in the incidence of malignant melanoma in Sweden, by anatomic site, 1960-1984.
This study was based on 15,376 patients in Sweden with cutaneous malignant melanoma diagnosed during the 25-year period 1960-1984. Trunk melanoma increased substantially during that period among men, with age-standardized rates rising from 1.1 to 7.0 per 10(5). Among women, the greatest increases occurred in melanoma of the upper extremity (rising from 0.4 to 2.3), lower extremity (rising from 1.6 to 4.4), and trunk (rising form 0.6 to 3.1), but the rates for the latter two sites seemed to level off after 1978. Multivariate analyses showed that models based on a common parameter ("drift"), including linear birth cohort and/or time periods effects, were significantly superior to simple age models for explaining incidence trends for each separate site. Further, in men with melanoma of the trunk and upper and lower extremities, birth cohort effects had significant effects compared with drift. In contrast, in women, time period effects were a significant improvement on drift for melanoma of the trunk and lower extremity. The relative risk of malignant melanoma among men leveled off in later-born cohorts for all separate sites. A similar trend was found in women, except for melanomas of the trunk, in which the increase in relative risk persisted. The results indicate sex-specific differences in temporal trends of exposure to factors causing malignant melanoma.
Adult↗
Dacarbazine-vindesine-cisplatin in disseminated malignant melanoma. A phase I-II trial.
Dacarbazine-vindesine-cisplatin treatment was evaluated in a phase II study of patients with disseminated malignant melanoma after the dose of cisplatin had been determined in a phase I study. Dose of dacarbazine was 250 mg/m2 X V every 4 weeks, vindesine 3 mg/m2 once every week, and cisplatin 100 mg/m2 every 4 weeks. Forty patients with advanced disseminated malignant melanoma are available for response. Complete remissions were obtained in three patients (8%) and partial remissions in 12 patients (30%). The total response rate was 38%. Median response duration was 4 months. Toxicity was unacceptable in five cases (nephrotoxicity, one patient; ototoxicity, two patients; hypotonia, one patient; gastrointestinal toxicity, one patient). The conclusion is that the combination dacarbazine-vindesine-cisplatin gives rise to a high response rate in patients with advanced disseminated malignant melanoma. Despite its considerable toxicity, the regimen should be tested on patients with a limited tumor burden.
Antineoplastic Combined Chemotherapy Protocols↗
Cell death in relation to cell cycle in a mouse ascites tumor growing in vivo after combined treatment with cisplatin and 5-fluorouracil.
The interaction of 5-fluorouracil (5-FU) and cisplatin (CDDP) was studied in Bp8 ascites sarcoma cells growing in mice. By density gradient centrifugation in Percoll solution, non-viable cells were separated from viable cells. Single drug treatment with doses of 12 and 36 mg/kg body weight of 5-FU and 0.4 and 0.8 mg/kg body weight of CDDP did not yield non-viable cells during the time period studied (96 h). Combination of the drugs increased the non-viable cells to about 10-25% depending on the doses given. This indicates a supra-additive cytotoxic effect. Analysis of the distribution of viable cells in the different cell cycle phases by flow cytometry showed an accumulation of cells in the S-phase after 5-FU and in the S- and G2-phases of the CDDP or combined 5-FU-CDDP treatment. Similar analysis of non-viable cells showed a similar cell cycle distribution, which suggests that supra-additive cytotoxicity is not cell cycle specific. By labeling the DNA of the tumor cells with [125T]-deoxyuridine and using whole body measurement, the cell loss was studied. No changes in cells loss after single drug and combined treatment were found during the observation time. The molecular basis for the interaction between 5-FU and CDDP should be elucidated.
Animals↗
Malignant melanoma: aetiological importance of individual pigmentation and sun exposure.
A case-control study of cutaneous malignant melanoma (CMM) was based on 523 incident cases and 505 age- and sex-matched controls selected from the general population. The purpose was to investigate the relative risk of developing CMM associated with different sun habits and indicators of pigmentation, such as skin type, eye colour and hair colour. Compared to people with black hair, blonde subjects had a relative risk of 74.4 (95% confidence interval, 45.8-120.8). Associations with skin type and eye colour were considerably weaker. Relative risks of about 1.5-2.5 were found for certain sun habits. The results suggest that in a population of Caucasian origin with a predominantly fair complexion, pigmentary status characterized by hair colour is a far more important aetiological factor than sun habits.
Eye Color↗
Comparison of anatomical location of squamous cell carcinoma within the oral cavity and oropharynx with the incidence of in vitro hyperdiploidy.
The anatomical location of the squamous cell carcinoma (SCCA) within the oral cavity and oropharynx influenced the association of SCCA with the biomarker in vitro hyperdiploidy in human dermal fibroblast cultures (IVH). There was a strong association of IVH with the occurrence of SCCA in the anterior 2/3 of the tongue, floor of the mouth and lower alveolar ridge of the oral cavity and in the base of the tongue and pharyngeal wall of the oropharynx. There was a lower association of SCCA with IVH in the tonsillar region of the oropharynx. IVH showed no association with SCCA located in other anatomical parts of the oral region. The patient group whose diagnosis of SCCA in the anterior 2/3 of the tongue occurred prior to the age of 50 years were invariably IVH-, whereas those diagnosed after the age of 50 years were IVH+, providing evidence for heterogeneity. There was no such correlation of biomarker subgrouping with age of diagnosis demonstrated for SCCA at any other anatomical location within the oral cavity or oropharynx.
Adult↗
Glutathione-linked enzymes in normal and tumor cells and their role in resistance against genotoxic agents.
Glutathione is the most abundant low molecular mass thiol in human cells. It is involved in the inactivation of genotoxic electrophilic compounds, and a variety of glutathione-linked enzymes catalyze such detoxication reactions. Within this group, the enzymes occurring in highest intracellular concentrations are the glutathione transferases, which catalyze the detoxication of a broad spectrum of alkylating and oxidizing compounds such as epoxides, reactive alkenes and organic hydroperoxides. Multiple forms of glutathione transferase with distinct substrate specificities exist, and their differential expression in cells contributes to differences in detoxication capacities in tissues. Glyoxalase I catalyzes the inactivation of 2-oxoaldehydes and may also be considered as part of the cellular detoxication system. Characterization of the different enzymes and their differential expression in normal and tumor cells will help to clarify their cellular functions and their significance to human cancer. Clear differences in the occurrence of the various enzyme forms in normal and tumor cells have been demonstrated and variations between different tumors appear to be linked to their degree of resistance to alkylating cytostatic drugs. Modulation of catalytic activities in vitro by administration of enzyme inhibitors may help to overcome this resistance.
Animals↗