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Biomedical subjects

M Edgren

Publications and source records attributed to M Edgren.

At least 37 records · Page 2Linked to original sources
PubMed1984

Glutathione-dependent yield and repair of single-strand DNA breaks in irradiated cells.

The yield and rejoining of single-strand DNA breaks (ssb) was investigated after irradiation of cells which were deficient in glutathione (GSH) either due to a genetic defect of their GSH synthetase activity, or inhibition of gamma-glutamylcysteine synthetase activity by DL-buthionine-SR-sulfoximine (BSO). The results were concordant in indicating that decreased cellular GSH content is associated with an increased yield of ssb after anoxic, but not after aerobic radiation exposures. Rejoining of ssb was delayed and incomplete during a one hour's incubation period after oxic, but not after anoxic exposure of GSH-deficient cells. The defective rejoining capacity of these cells was restituted to nearly normal by the admixture of GSH-proficient cells in the incubation medium.

Buthionine Sulfoximine↗
PubMed1981

Induction and repair of single-strand DNA breaks after X-irradiation of human fibroblasts deficient in glutathione.

Using the unwinding technique in weak alkali, the induction and repair of DNA single-strand breaks was determined after aerobic and anerobic X-irradiation of human fibroblasts, obtained from a patient suffering from 5-oxoprolinuria, and from a clinically healthy control. The metabolic disorder associated with 5-oxprolinuria is a deficiency in glutathione synthetase activity resulting in a greatly reduced glutathione content in the cells. A small dose-modifying effect of oxygen (o.e.r. = 1.1) was found for these cells in comparison to an o.e.r. of 2.5 for control cells with normal glutathione content. No significant difference was found between the repair capacity of cells with normal and deficient glutathione content, and repair was nearly completed within 60 min of anoxic irradiation in each case. In contrast, after aerobic irradiation of glutathione-deficient cells repaired less than 70 per cent of the breaks during the same period. When the glutathione-deficient cells were incubated with either dithiothreitol or mercaptopropionylglycine directly after aerobic irradiation, almost complete repair was obtained within 60 Min. The data are interpreted as indicating that the repair mechanism for oxically and anoxically induced single-strand breaks is qualitatively different, and requires glutathione in the former case.

Adult↗
PubMed1981

Oxygen enhancement of radiation induced lethality is greatly reduced in glutathione deficient human fibroblasts.

The in vitro clonogenic survival of human fibroblasts with a genetically defined glutathione (GSH) deficiency was studied after irradiation with X-rays in oxygen or in oxygen free argon. Genetically related fibroblasts without GSH deficiency were used as a control. The oxic survival curve of both cell lines was similar. In comparison to the oxic survival curve, the anoxic survival curve of GSH deficient cells indicated an oxygen enhancement ratio (OER) approximately 1.5. An OER approximately 2.9 was calculated in comparing the oxic and anoxic survival curves of the control cell line. The results were discussed in support of the theory according to which oxygen and GSH compete for radiation induced radicals in key molecules, the former irreversibly fixing and the latter repairing the radiation damage.

Anaerobiosis↗
PubMed1980

Lack of oxygen effect in glutathione-deficient human cells in culture.

The frequency of X-ray-induced DNA breaks was determined in human cell lines which are deficient in glutathione synthetase and have a greatly reduced glutathione content. Hydroxyapatite chromatography was used for the estimation of the DNA breaks in cell cultures, which were derived either from lymphoblasts transformed by infection with EB virus or from fibroblasts. The dose-effect relationship for the induction of breaks when radiation exposure was made in argon, was similar to that found when exposure was made in air. In control cultures with normal glutathione content, the induction of breaks was enhanced when irradiation was made under aerobic, instead of anaerobic, conditions. Treatment of the glutathione-deficient cells with the hypoxic radiosensitizer misonidazole did not enhance the induction of breaks by radiation delivered either in air or in argon. In control cultures, radiation induction of breaks was enhanced by misonidazole under anaerobic but not under aerobic conditions. When the glutathione-deficient cells were pretreated with cysteamine however, irradiation in the absence of oxygen resulted in a decreased frequency of DNA breaks.

Cells, Cultured↗
PubMed1977

Effect of radioprotective aminothiols on the induction and repair of single-strand breaks in the DNA of irradiated mammalian cells.

The effect of cysteamine and 2-mercapto-propionyl-glycine on the induction and repair of single-strand breaks in the DNA of Chinese hamster cells by irradiation in vitro in the presence of oxygen or in anoxia was investigated. The substances protected against the formation of breaks by irradiation both under oxic and anoxic conditions. The substances also exhibited a toxic effect which resulted in degradation of DNA. Cysteamine inhibited the rejoining of breaks after radiation exposure.

Amino Acids, Sulfur↗
PubMedDate not supplied

Serum concentrations of VEGF and b-FGF in renal cell, prostate and urinary bladder carcinomas.

Sixty nine patients with urogenital cancers (renal, bladder and prostate cancer) were studied to determine whether the serum concentrations of Vascular Endothelial Growth Factor (VEGF) and basic Fibroblast Growth Factor (b-FGF) reflected the status of the patients and/or the prognosis of the disease. Of the patients included in this study, renal cell carcinoma patients expressed the highest levels of VEGF indicating that these tumours are more VEGF dependent. The values of b-FGF could be considered normal in all three malignancies. No correlation was observed between the expression of VEGF and b-FGF, nor between VEGF and b-FGF and patients survival.

Adult↗
PubMedDate not supplied

Human milk fat globule antigen 1 (HMFG1) expression in prostatic carcinoma and immunotargeting with a radiolabelled monoclonal anti-HMFG1 antibody.

BACKGROUND: Prostatic cancer is the leading cause of death in Swedish men. Approximately 50% have disseminated disease at diagnosis. Radiolabelled antibodies could possibly be a treatment modality for disseminated prostatic cancer, so that in this study the expression of the human milk fat globulin 1 (HMFG1) antigen in prostate cancer was examined. MATERIALS AND METHODS: An immunohistochemistry technique with a murine monoclonal antibody was used, as well as the human prostate cancer cell line DU-145, which expresses this cell surface antigen. TUR specimens from patients with prostate cancer were also examined. RESULTS: Eighteen out of 22 (82%) patients exhibited an HMFG1-positive tumour. An inhomogenity in the immunostaining could occasionally be seen, with smaller apparently negative areas. The immunolocalisation properties of the antibody were investigated using a radiolabelled antibody injection into nude mice bearing heterotransplants of the DU-145 cell line. The highest accumulation of the antibody was seen in the tumour tissue and the liver. CONCLUSION: The results obtained form a basis for further investigations with the goal of using the antibodies for staging and therapy for prostate cancer.

Animals↗
PubMedDate not supplied

Estramustine a radio sensitising agent.

The present study revealed that estramustine acts as a radio sensitising agent on the human renal cell cancer cell lines, A498 and CAKI-2. In vitro experiments used the Bürker chamber technique. Both cell lines were markedly resistant to external beam irradiation. While pretreatment of the cell cultures with estramustine prior to external beam irradiation revealed an arrest of cell growth in both cell lines. The results of this study suggest that estramustine could be utilised as a radiosensitizing agent. This in turn could open a new method for the management of patients with advanced renal cell carcinoma (RCC).

Antineoplastic Agents↗
PubMedDate not supplied

Angiogenic factors: vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (b-FGF) are not necessarily elevated in patients with advanced renal cell carcinoma.

Serum analysis of Vascular Endothelial Growth Factor (VEGF) and basic Fibroblast Growth Factor (b-FGF) levels were studied in 53 patients with renal cell carcinoma (RCC). Approximately 2/3 of the patients had disseminated disease at diagnosis, the remainder had no evidence of metastases. The results confirmed that VEGF has a major role in the angiogenesis of RCC. No correlation was observed between VEGF and/or b-FGF and the presence or absence of metastases, nor was any correlation observed between VEGF and/or b-FGF and patient survival. Thus, to utilise VEGF and/or b-FGF as a tumour marker at the time of diagnosis to predict patients with a high risk of progression, where an adjuvant therapeutic approach would be of great value, seems to be limited. Not all patients with RCC exhibited elevated serum levels of VEGF and/or b-FGF. No correlation was observed between tumour stage and serum levels of these angiogenic peptides.

Adult↗
PubMedDate not supplied

Postoperative radiotherapy after prostatectomy can be associated with severe side effects.

This retrospective study was initiated to evaluate the efficacy and side effects of post-prostatectomy external beam radiation therapy (XRT) with a short time interval between surgery and irradiation in patients with prostate adenocarcinoma. Sixteen patients were investigated. The overall results in this study were 3 deaths due to recurring disease and two relapses after an average follow-up of 60 months. Severe side effects were observed. Two patients required surgical intervention due to severe post-radiotherapy side effects. The reason for this could be the high dose delivered to peripheral organs and/or a too short time interval between surgery and postoperative XRT. The results of this study confirmed that postoperative XRT can improve local control frequency in prostate carcinomas. It is recommended that the time interval between surgery and postoperative radiotherapy should to be 3-6 month.

Adenocarcinoma↗
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↗