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Biomedical subjects

U Ringborg

Publications and source records attributed to U Ringborg.

At least 37 records · Page 2Linked to original sources
PubMed1989

Trends in survival from malignant melanoma: remarkable improvement in 23 years.

Trends in incidence of and mortality and survival from malignant melanoma in Sweden for 1960 through 1982 were analyzed. Incidence rates increased annually by 5.4% for females and by 5.8% for males, whereas mortality rates increased annually by 2.7% for females and 3.3% for males. For females, the 5-year relative survival (RS) rates increased by approximately 15 percentage points before 1970. In contrast, males before 1970 had a successive improvement in RS rates of 4.6-8.2 percentage points for each 5-year period of diagnosis. Multivariate analyses revealed that during the study period the malignant melanoma-specific hazard decreased by 71% [95% confidence interval (CI) = 59%-79%] for females and by 64% (95% CI = 54%-73%) for males during the first 5 years of follow-up.

Aged↗
PubMed1989

Dacarbazine versus dacarbazine-vindesine in disseminated malignant melanoma: a randomized phase II study.

In a phase II study 119 patients with disseminated malignant melanoma were randomized to receive treatment with dacarbazine alone or in combination with vindesine. The study was designed to reveal an additive response rate when the drugs were combined. Dacarbazine was given i.v. at 250 mg m-2 per day X V every 4 weeks. In the combination regimen vindesine given at 3 mg m-2 per week was included. One hundred and ten patients were available for evaluation of response. With dacarbazine 4/51 patients obtained a complete remission (8%) and 5/51 patients a partial remission (10%). Overall response rate was 18%. With dacarbazine-vindesine 8/59 patients obtained a complete remission (13%) and 7/59 patients a partial remission (12%). Overall response rate was 25%. The difference in response rates observed between the treatment arms is not statistically significant. Median response duration was 123 days for dacarbazine patients and 171 days for patients receiving dacarbazine-vindesine (difference not statistically significant).

Adult↗
PubMed1989

The association between anatomic site and survival in malignant melanoma. An analysis of 12,353 cases from the Swedish Cancer Registry.

The relationship between site and survival in cutaneous malignant melanoma was investigated by a follow-up of 12,353 Swedish patients diagnosed in 1960-1982. In males, the poorest prognosis was found for tumors located on the scalp-neck region (5-year relative survival rate, RS51%), followed by the lower extremity (RS66%) and trunk (RS68%). Among females, the poorest prognosis was noted for tumors located on the external ear (5-year RS 71%), trunk (RS 78%) and scalp-neck (RS 78%). The prognosis varied considerably between the sites of the head-neck region--for eyelid and facial lesions the prognosis was good, but for external ear and scalp-neck tumors it was poor. Multivariate analysis taking into account age and year of diagnosis showed the highest relative hazards (RH) for female lesions of the trunk (1.40) and male scalp-neck tumors (1.65), with the upper extremity used as reference (RH = 1.00). Except for lesions of the trunk, no significant differences in RH were found between the various sites after 4 years of observation.

Adult↗
PubMed1989

Adjuvant chemotherapy with doxorubicin in high-grade soft tissue sarcoma: a randomized trial of the Scandinavian Sarcoma Group.

From January 1981 to February 1986, a total of 240 patients with primary, malignancy-grade III or IV soft tissue sarcoma were entered into an adjuvant chemotherapy multicenter trial conducted by the Scandinavian Sarcoma Group (SSG). Of these patients, 181 were evaluable. The tumor was located in the extremities in 155 patients. After radical surgery (wide and compartmental) the patients were randomized to treatment with single-agent doxorubicin 60 mg/m2 administered as an intravenous (IV) bolus once a month for 9 months (group 1, n = 77) or to control (group 2, n = 77). If the surgical procedure was marginal, the patients initially received postoperative radiotherapy, followed by doxorubicin (group 3, n = 16) or control (group 4, n = 11). The control groups did not receive any adjuvant chemotherapy. Adjuvant therapy was initiated within 6 weeks of surgery (group 1) or within 10 weeks of surgery for patients receiving postoperative radiotherapy (group 3). With a median follow-up of 40 months, there was no significant difference between the four treatment groups in overall survival (group 1, 75%; group 2, 70%; group 3, 69%; group 4, 73%), disease-free survival (group 1, 62%; group 2, 56%; group 3, 62%; group 4, 64%), or local tumor control (group 1, 92%; group 2, 92%; group 3, 87%; group 4, 90%). The conclusions were the same whether the total group or evaluable patients only were included in the analysis. The local recurrence rate for patients undergoing radical surgery was 8% and for patients undergoing marginal surgery followed by radiotherapy was 12%. This study indicates that the use of single-agent doxorubicin as postoperative adjuvant chemotherapy has no significant clinical benefit in patients with high-grade soft tissue sarcoma.

Adolescent↗
PubMed1989

Treatment of keloids with surgical excision and postoperative X-ray radiation.

124 patients with keloids were treated with surgical excision followed by postoperative X-ray radiation, begun within 24 hours after surgery. Only patients with a two-year keloid history were included in this study. The treatment results were evaluated 6 and 24 months after treatment. There was good correlation agreement between subjective and objective evaluations. Good or excellent results were observed in 92% of the patients. Side effects were moderate. Slight hyperpigmentation was found in 31% of the patients and telangiectasis in 15%. It was concluded that excision and early postoperative irradiation constitute effective keloid treatment.

Adult↗
PubMed1988

Effect of D,L-buthionine-S,R-sulfoximine on cytotoxicity and DNA cross-linking induced by bifunctional DNA-reactive cytostatic drugs in human melanoma cells.

The effects of D,L-buthionine-S,R-sulfoximine (BSO) on cytotoxicity and DNA cross-linking induced by bifunctional DNA-reactive cytostatic agents in a human melanoma cell line (RPMI 8322) were investigated. RPMI 8322 cells were exposed to 0.01 mM BSO for 24 h, which resulted in a decrease in cellular glutathione to 14% without any reduction of cell proliferation or plating efficiency. BSO pretreatment significantly enhanced cytotoxicity of melphalan with a dose modification factor (DMF) of 3.4 and nitrogen mustard (HN2) (DMF 3.3). The increased cytotoxicity was paralleled by similar increases in DNA cross-linking (melphalan: DMF 2.2, HN2: DNF 2.5). A small but significant potentiation by BSO of cis-diamminedichloroplatinum(II) toxicity was seen (DMF 1.5), with a corresponding minor but significant increase in DNA cross-linking (DMF 1.1). Similarly, the potentiation of bis-chloroethylnitrosurea toxicity was small but significant (DMF 1.1), with no significant increase in DNA cross-linking (DMF 1.0). No effect of BSO pretreatment on the rate of removal of HN2-induced DNA cross-links was observed. Thus, the observed sensitization of RPMI 8322 cells to melphalan, HN2, cis-diamminedichloroplatinum(II), and bis-chloroethylnitrosourea was correlated to similar changes in drug-induced DNA cross-linking. Despite the increased cytotoxicity and DNA cross-linking BSO did not significantly increase the intracellular concentration of intact melphalan. These findings support the hypothesis that the potentiation of the cytotoxicity of bifunctional alkylating agents by BSO is due to an increased DNA cross-linking caused by a reduced intracellular conjugation of drug with glutathione, which results in an increased binding of drug to DNA targets.

Antineoplastic Agents↗
PubMed1988

Concentration and time-dependent inter-relationships for cytotoxicities of nitrogen mustard drugs against lymphoblasts in-vitro.

Peripheral lymphoblasts were exposed either to different initial concentrations of the alkylating agents (melphalan, chlorambucil or phenylacetic acid mustard) using a fixed incubation time or a constant [3H]methylthymidine incorporation into the trichloracetic acid-insoluble fraction of the cells. The concentration-time relationships were evaluated by calculating the amount of drug which had chemically reacted in the incubation system. Melphalan showed lower cytotoxicity at short exposure times and high drug concentrations, while chlorambucil exhibited higher cytotoxicity at longer exposure times. In the latter case the effect could be accounted for by the cytotoxic activity of monohydroxy chlorambucil which was formed in the incubation system.

Cell Survival↗
PubMed1988

Cis-diamminedichloroplatinum(II) toxicity in human melanoma cells and lymphocytes as related to cellular platinum accumulation, DNA cross-linking and inhibition of DNA synthesis.

The cytotoxic effect of cis-diamminedichloroplatinum(II) (cis-DDP), as measured by a dye exclusion assay was much more pronounced in bone marrow cells and phytohemagglutinin (PHA)-stimulated lymphocytes than in a human melanoma cell line. DNA synthesis measured by incorporation of 3H-thymidine was much more sensitive to cis-DDP in PHA-stimulated lymphocytes than in melanoma cells. These differences were not caused by a difference in drug accumulation since measurements of cellular platinum content gave similar results in both cell types. The total amount of DNA cross-links and DNA interstrand cross-links induced by cis-DDP was measured with alkaline elution of DNA. In both PHA-stimulated lymphocytes and melanoma cells low total levels of DNA cross-links and DNA interstrand cross-links were found immediately after drug exposure, followed by a protracted increase in DNA cross-linking for 6-12 hours during further incubation after removal of cis-DDP. The relationship between the concentration of cis-DDP and peak levels of total DNA cross-links as well as DNA interstrand cross-links was linear in both cell types. Cis-DDP was found to induce 5.6 times higher total levels of DNA cross-links 6.1 times higher levels of DNA interstrand cross-links in PHA-stimulated lymphocytes than in melanoma cells. The incorporation of 3H-thymidine was much more reduced in PHA-stimulated lymphocytes than in melanoma cells at similar levels of DNA cross-linking. Thus, both reduced DNA cross-linking and lower effect of DNA cross-links on the DNA synthesis may contribute to the greater resistance of melanoma cells to cis-DDP.

Cell Line↗
PubMed1987

Evidence for genetic predisposition for some nasopharyngeal cancers by in vitro hyperdiploidy in human dermal fibroblasts.

A numerical alteration in chromosome complement in human dermal fibroblast cultures, hyperdiploidy with a normal occurrence of tetraploidy (IVH), has been reported to be associated with some hereditary single tumors including squamous carcinoma of the nasopharynx (NPC). Its incidence was compared in cultures derived from 39 NPC patients and 29 clinically normal subjects without a family cancer history by two different methods (percentage of numerically altered metaphases in chromosome preparations from nonconfluent monolayer Petri dish cultures in logarithmic growth, and by the distribution of DNA content of propidium iodide stained cells from plastic flask cultures in stationary growth phase as assayed by flow cytometry) to ascertain its usefulness in identification of such genetic predisposition. Concordance was observed between the two assays. There was a linear relationship between the percentage of hyperdiploid metaphases assayed in the chromosome preparations and the percentage of cells with a DNA index of greater than 1 as determined by flow cytometry. By metaphase assay, none of the 29 normals showed IVH. OF the 39 carcinoma of the nasopharynx patients studied, 19 had IVH and 20 did not. By flow cytometry there were significant differences in the flow cytometry DNA index (p less than 0.001) of IVH-negative (all normals and 20 carcinoma of the nasopharynx patients) and IVH-positive carcinoma of the nasopharynx patients. The percentage of cells with a DNA index of 2 and greater than 1 could be used to distinguish all IVH-negative from the IVH-positive subjects and, thus, were considered to be the parameters of choice in assaying IVH by flow cytometry. None of the subjects studied showed increased in vitro tetraploidy (IVT), which has been associated with some heritable colon cancer syndromes. Irrespective of family cancer history, approximately one-half of the NPC patients (19 of 39) had IVH, which has been reported to be associated with the in vivo expression of certain heritable tumors including carcinoma of the nasopharynx. The average age of carcinoma of the nasopharynx diagnosis was earlier (mean 52 yr) for the IVH-positive group than for the IVH-negative carcinoma of the nasopharynx group (mean 67 yr).

Adult↗
PubMed1987

Expression of class Pi glutathione transferase in human malignant melanoma cells.

The occurrence of glutathione transferase in human malignant melanoma cell lines and solid tumor material has been analyzed and compared with the enzyme composition in fibroblasts and naevus samples. All cells and tissues investigated contained essentially only the acidic class Pi glutathione transferase as demonstrated by SDS-PAGE and immunoblotting. The enzyme was purified from tumor material and characterized. Its intracellular concentration was significantly higher in all the melanoma cell preparations analyzed than in the non-malignant cells, supporting the view that the class Pi glutathione transferase may contribute to the drug resistance that is characteristic of malignant melanoma.

Breast Neoplasms↗
PubMed1987

Long-term survival in malignant melanoma with special reference to age and sex as prognostic factors.

A total of 12,353 (97.5%) of all patients with a first malignant melanoma newly diagnosed in Sweden during the period 1960-82 were subjected to a complete computerized follow-up with respect to survival through December 31, 1982. Calculation of relative survival rates (RSs) revealed a consistently more favorable course in women than in men, the 5-year RSs being 80.8 and 68.0% and the 10-year RSs being 75.0 and 61.8%, respectively. Prolonged follow-up and analyses of annual excess mortality showed, in addition, that men surviving about 10 years constituted an apparently cured fraction, whereas among women there was an excess mortality throughout the observation period. The prognosis was increasingly more favorable at younger ages in males, whereas no regular age trend emerged in the female group of patients. A multivariate analysis indicated that the findings were not confounded by temporal trends in RSs or by differences in tumor location between the groups compared and also that the relative hazard was significantly higher for men than for women only during the first 8 years after diagnosis.

Adult↗
PubMed1979

Absence of genotoxic effects of metronidazole and two of its urinary metabolites on human lymphocytes in vitro.

The antiprotozoan agent metronidazole (1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole) and two of its major human urinary excretion products, 2-methyl-5-nitromidazole-1-yl acetic acid and 1-(2-hydroxyethyl)-2-hydroxymethyl-5-nitroimidazole were tested for genotoxic activity in human lymphocytes in vitro by analysis of chromosome aberrations, sister-chromatid exchanges and DNA-repair synthesis. The positive control compounds methyl methanesulphonate (MMS) and nitrogen mustard (HN2) showed significant genotoxic activity in these tests. No such activity of metronidazole and its two metabolites was detected in concentrations up to 1000 microgram/ml (5.8 X 10(-3) M). Nor did these 3 compounds influence DNA-repair synthesis induced by MMS and HN2. These results suggest that metronidazole, 2-methyl-5-nitroimidazole-1-yl acetic acid and 1-(2-hydroxyethyl)-2-hydroxymethyl-5-nitroimidazole have no direct genotoxic effect on human lymphocytes in vitro.

Chromatids↗
PubMed1979

Age-related decrease of ultraviolet light-induced DNA repair synthesis in human peripheral leukocytes.

The capacity for ultraviolet light-induced DNA repair synthesis, studied in peripheral leukocytes from 58 healthy subjects 13 to 94 years old, was found to vary greatly between individuals. A negative, statistically significant correlation was obtained between age and this synthesis, indicating a decrease in repair capacity with age. An age-related decrease in DNA repair may increase the susceptibility of cells to agents causing DNA damage, i.e. carcinogens and certain cytostatic drugs.

Adolescent↗
PubMed1979

Induction of unscheduled DNA synthesis in human bone marrow cells by bifunctional alkylating agents.

A technique has been developed for handling human bone marrow cells intended for the examination of DNA repair synthesis. DNA-repair synthesis, induced by melphalan and nitrogen mustard, was measured as the incorporation of 3H-thymidine, registered by autoradiography as unscheduled DNA synthesis (UDS). Comparison of various cell populations disclosed considerable differences in their UDS level, this generally being greatest for the blast populations. During maturation of both myelopoietic and erythropoietic cells, there was a decrease in the UDS level, which was lowest for the end-cell stage. The lymphocytes and monocytes differed considerably in their capacity for UDS. The developed technique would appear to offer an opportunity for determining the capacity for DNA-repair synthesis in malignant bone marrow cells, a factor that has been linked to sensitivity to alkylating agents.

Alkylating Agents↗
PubMed1978

Factors responsible for bone marrow toxicity after treatment of myeloma patients with different alkylating agents.

Leukopenia and thrombocytopenia were studied after loading doses of melphalan (5 mg/daily for 18-25 days) in 71 myeloma patients. Seventy per cent of the patients developed pronounced leukopenia (white cells less than 2.0 X 10(9)/l) and/or thrombocytopenia (platelets less than 100 X 10(9)/l). The patients with pronounced and moderate hematological side-effects, respectively, were compared for weight and age. The body weight was the same in the two groups, indicating that the patient's weight is of minor importance for the dosage of melphalan. There was a numerical difference in age, on the borderline for statistical significance, indicating that the age of the myeloma patient may be of minor importance for the dosage of melphalan. It is possible that more pronounced age differences may be of greater importance in this respect. Fifteen patients with myeloma were treated with cyclophosphamide. Compared with melphalan, the effect on white cells was the smae, while the incidence of thrombocytopenia was statistically significantly lower with cyclophosphamide.

Aged↗