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Biomedical subjects

U Ringborg

Publications and source records attributed to U Ringborg.

At least 109 records · Page 6Linked to original sources
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

Differential DNA cross-linking and cytotoxicity in PHA-stimulated human lymphocytes exposed to melphalan, m-L-sarcolysin and peptichemio.

DNA interstrand, as well as DNA protein cross-linking, was more efficient in phytohaemagglutinin-stimulated human lymphocytes exposed to m-L-sarcolysin as compared to melphalan at equivalent concentrations of the drug. The cellular uptake of m-L-sarcolysin was more efficient as compared to melphalan. With peptichemio, a mixture of 6 peptides containing m-L-sarcolysin, an intermediate level of DNA cross-linking was found. The differences in DNA cross-linking between the 3 drugs were parallel to differences in cytotoxicity. Peptichemio has been ascribed anti-metabolic properties in addition to the alkylating properties conferred by its m-L-sarcolysin content. In the phytohaemagglutinin-stimulated lymphocytes, however, the effect of peptichemio seems linked to its capacity for DNA cross-linking.

Cell Survival↗
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

In vitro hyperdiploidy in dermal fibroblasts: evidence for genetic predisposition in aerodigestive tract cancer.

A numerical alteration in chromosome complement in human dermal fibroblast cultures, hyperdiploidy with a normal occurrence of tetraploidy (IVH) has been reported (Danes 1984) to be associated with some heritable single tumors including squamous carcinoma of the nasopharynx (Danes 1986). The incidence of IVH was compared in cultures derived from 65 patients with squamous carcinoma in different regions of the aerodigestive tract (ADT) and 32 clinically normal subjects without a family cancer history by 2 different assays, metaphase assay (MA) and flow cytometry (FCM). By MA, none of the 32 normals showed IVH. Of the 65 ADT patients studied, 35 had IVH and 30 did not. By FCM, there were significant differences in the FCM DNA index (p values less than 0.001) of IVH- (all normals and 30 ADT patients) and IVH+ ADT patients. The per cent of cells with a DI of 2 and greater than 1 could be used to distinguish all IVH- from the IVH+ subjects and were thus considered to be the parameters of choice in assaying IVH by FCM. 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 half (35/65) of the ADT patients had IVH which has been shown to be associated with the in vivo expression of certain heritable tumors. The average age of squamous carcinoma diagnosis was earlier (mean 50 yrs) for the IVH+ group than for the IVH- ADT group (mean 72 yrs).

Adolescent↗
PubMed1987

Effect of 5-fluorouracil on the cell growth and cell cycle kinetics of a mouse ascites tumor growing in vivo.

The effect of 12, 24 and 36 mg/kg body weight doses of fluorouracil (5-FU) on the Bp 8 ascites sarcoma growing in vivo was studied. From sequential studies of the total number of cells together with the composition of cells in the cell cycle, the cell cycle flow was calculated and correlated to the pharmacokinetics, which was determined by using 3H-5-FU. The dose of 12 mg/kg 5-FU affected cell growth between 24 and 72 hours, while the effect of higher doses was immediate. An early block in outflow of cells from G1 was followed by an increased outflow, indicating an early inhibition followed by an enhancement of the initiation of the DNA synthesis. This increased outflow from G1 together with the decrease in outflow from the early S-phase, i.e. decreased DNA synthesis, resulted in an accumulation of cells in the early part of the S-phase. The prolonged effects on the cell growth and the cell cycle flow despite the very fast decline in the drug concentration both in the ascites fluid and within the cells, together with a constant level of the drug in the macromolecular fraction, suggest an interaction between 5-FU and RNA/DNA at later times rather than an inhibition of the thymidylate synthetase activity.

Animals↗
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↗
PubMed1985

Adjuvant chemotherapy of malignant melanoma. A pilot study.

In a pilot study, 26 patients with stage I malignant melanoma, tumor thickness greater than 2.25 mm, and/or Clark level IV, and Stage II tumors were randomized to adjuvant chemotherapy with either DTIC, DTIC/CCNU/vincristine, or to a control group with no further treatment after surgery. The chemotherapy group contained 17 patients and the control group nine patients. The follow-up time is 37-54 months. The recurrence-free and overall survival is significantly longer in the patient group treated with adjuvant chemotherapy as compared to controls (p less than 0.025, according to the log-rank test).

Adult↗
PubMed1983

Epstein-Barr virus-specific serodiagnostic tests in carcinomas of the head and neck.

Sera from 256 patients with cancers of the head and neck were examined for their profiles of IgG and IgA antibodies to Epstein-Barr virus (EBV)-specific, viral capsid antigen (VCA), the diffuse (D) and the restricted (R) components of the early antigen (EA) complex, and the EBV-associated nuclear antigen (EBNA), in order to assess the value of these procedures in the routine diagnosis of poorly or undifferentiated nasopharyngeal carcinoma (NPC). In 13 NPC patients, the carcinoma had invaded cervical lymph nodes, and their sera revealed, in addition to high IgG anti-VCA titers, elevated levels of IgA antibodies to VCA, of IgG antibodies to D, and most also had IgA anti-D. Such profiles were seen in very few of the patients with carcinomas at other sites of the head and neck. They had not developed in four NPC patients whose tumors were limited to the postnasal space, and in three patients with other tumors at that site. Among 15 patients with cervical node metastases from occult primary tumors, 2 had EBV-specific antibody profiles compatible with NPC, 1 was judged to have NPC on clinical grounds, and the other died of a pulmonary carcinoma, or possibly pulmonary metastases. In 4 of the remaining 13 patients with occult tumors, the primary site was found outside the nasopharynx, whereas it escaped detection in the other 9. These results lend further support to the usefulness of the EBV-specific serology to clinicians in the diagnosis of NPC, especially in cases of lymph node invasion by undetected primary tumors. The data also emphasize the need of complementing the serology with the examination of biopsies for the presence of EBV deoxyribonucleic acid (DNA) or, more readily performed, EBNA-positive carcinoma cells.

Aged↗
PubMed1983

Sequential methotrexate-5-fluorouracil treatment of squamous cell carcinoma of the head and neck.

Thirty-six patients with squamous cell carcinoma of the head and neck were treated with sequential methotrexate-5-fluorouracil followed by leucovorin rescue. The frequency of objective tumor regression obtained was 64% (complete response + partial response) with 19% complete regression. In 20 not previously treated patients, the objective response rate was 70%. Approximately the same result was obtained for tumors of different anatomical sites of the head and neck. The degree of differentiation of the squamous cell carcinoma did not seem to be of prognostic importance for the initial tumor response. Toxicity was very mild and usually disappeared when the interval between the chemotherapy courses was prolonged from 1 to 2 weeks. Radiotherapy could be added sequentially to the treatment without measurable escalated toxicity.

Carcinoma, Squamous Cell↗
PubMed1983

DNA repair replication, DNA breaks and sister-chromatid exchange in human cells treated with adriamycin in vitro.

The effects of adriamycin (AM) on DNA repair replication, the frequency of sister-chromatid exchange (SCE), the rate of cell proliferation and the frequency of DNA strand breaks were studied in human cells in vitro. No repair replication was observed in lymphocytes exposed to AM in concentrations up to 10(-3) moles/l. DNA repair replication induced by UV and alkylating agents was not affected by a concentration of AM that completely inhibited cell proliferation (10(-6) moles/l). Fibroblasts exposed to AM at 10(-4) moles/l in the presence of hydroxyurea showed an increase of strand breaks and cross-links in DNA. When AM was added to UV-irradiated fibroblasts, there was an increase of DNA strand breaks in addition to the breaks caused by UV alone. Similar effects were observed in lymphocytes. A dose-dependent increase of SCE was observed in lymphocytes exposed to low concentrations of AM (less than 10(-7) moles/l). At higher concentrations the increase of SCE levelled off, and cell proliferation became severely inhibited. There was no evidence of removal of SCE-inducing damage in cells exposed to AM during G0 or G1. The level of SCE induced in the third cell cycle after treatment with AM was not different from that induced during the first two cell cycles. These results suggest that the various genotoxic and cytotoxic effects of AM are caused by different types of cellular damage. Moreover, AM-induced DNA damage persists for several cell cycles in human cells in vitro and seems to be resistant to repair activity.

Cell Cycle↗
PubMed1983

Inhibition of nitrogen mustard induced DNA repair synthesis by anthracyclines in human peripheral leukocytes.

DNA repair synthesis was induced by nitrogen mustard in human peripheral leukocytes. When the cells were treated with increasing doses of doxorubicin or daunorubicin a decrease of the DNA repair synthesis was recorded. Daunorubicin had a significantly higher inhibitory effect on the DNA repair synthesis compared to doxorubicin. The inhibitory effect by doxorubicin or daunorubicin on nitrogen mustard induced DNA repair synthesis was compared with the inhibitory effect on replicative DNA and RNA synthesis in human lymphoblasts. The inhibition of DNA repair synthesis was significantly lower than the inhibition of replicative DNA synthesis and RNA synthesis for both drugs.

Cells, Cultured↗
PubMed1983

Preoperative radiation therapy of high malignancy grade soft tissue sarcoma. A preliminary investigation.

Twenty-three patients with high malignancy grade soft tissue sarcoma received irradiation (about 40 Gy) followed by surgery. The follow-up time was 62 months or more in all patients. The local recurrence rate was 9 per cent (2/23). One of the patients was reoperated and is living free of disease, giving a local control rate of 95 per cent. Thirty per cent (7/23) of the cases developed distant metastases and died of the disease. Delayed wound healing was observed in 2 cases which was possibly due to the radiation therapy. Since surgery was regarded non-radical in 5 cases, the local control obtained by the combined radiation therapy and surgery is good and should be the subject for further investigations.

Adult↗
PubMed1983

Methotrexate and 5-fluorouracil in head and neck cancer.

Since experimental data strongly suggest a synergistic cytotoxic effect when methotrexate (MTX) and 5-fluorouracil (5-FU) are administered sequentially, we investigated antitumor effects and toxicity with sequential MTX/5-FU followed by leucovorin rescue in 52 patients with carcinoma of the head and neck. MTX (200 mg/m2) was given as an i.v. infusion over 1 hr. At 2 hr, 5-FU (600 mg/m2) was started as an i.v. infusion for 2 hr. At 24 hr, the leucovorin rescue was started. The chemotherapy course was repeated every week until toxicity (mainly gastrointestinal) occurred, after which the interval between courses was prolonged to 2 wk. Toxicity was mild and usually disappeared when the interval between the chemotherapy courses was prolonged to 2 wk. The regression rate was 15% for complete and 48% for partial regression (response rate, 63%). In 31 of the patients not previously treated, the objective response rate was 74%. About the same results were obtained for tumors of different anatomic sites of the head and neck. Radiotherapy could be added sequentially without measurable escalation of toxicity. We conclude that sequential MTX/5-FU treatment, which produces a very mild toxicity to normal tissue, is effective in inducing antitumor response in patients with carcinoma of the head and neck.

Carcinoma, Squamous Cell↗
PubMed1982

DNA-repair synthesis in blast cells from patients with acute myeloblastic leukaemia.

DNA-repair synthesis was studied in blast cells from patients with acute myeloblastic leukaemia. The DNA-repair synthesis, measured as 3H-thymidine incorporation, was registered as unscheduled DNA synthesis by autoradiography, and also after suppression of the replicative DNA synthesis by hydroxyurea by liquid scintillation. There was good correlation when results from both methods were compared. A significantly wider variation of unscheduled DNA synthesis was found in leukaemic as compared to normal blast cell populations. There was also a wider variation within individual leukaemic blast cell samples compared to normal samples. A correlation was found between unscheduled DNA synthesis induced by nitrogen mustard and by UV-irradiation in the leukaemic blast cell populations. The UV-induced unscheduled DNA synthesis in some of the leukaemic blast cell populations continued to increase at doses of UV-irradiation at which normal myeloblasts had reached their maximum level of unscheduled DNA synthesis. This indicates that at least some malignant blast cell populations may possess an effective DNA-repair system.

Alkylating Agents↗
PubMed1982

DNA repair synthesis in subpopulations of human lymphocytes.

Human peripheral blood lymphocytes enriched in T or B cells were exposed to ultraviolet irradiation, nitrogen mustard or methylmethane sulphonate and investigated regarding their capacity for DNA repair synthesis. The DNA repair synthesis, measured as [3H] thymidine incorporated, was determined by autoradiography as unscheduled DNA synthesis (UDS). No systematic difference could be found in the capacity for UDS between the T- and B-cell-enriched fractions. A larger individual variation in UDS was found in the B-cell- compared to the T-cell-enriched lymphocytes.

B-Lymphocytes↗