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Biomedical subjects

R Henriksson

Publications and source records attributed to R Henriksson.

205 records · Page 12Linked to original sources
PubMedDate not supplied

Inhibition of growth of HeLa cell tumours in nude mice by 125I-labeled anticytokeratin and antiPLAP monoclonal antibodies.

The radiommunotherapeutic potential of 125I-labeled monoclonal antibodies was investigated in 48 nude mice (BALB/c, nu/nu) inoculated s.c. with the HeLa Hep 2 human adenocarcinoma cell line. This isotope, 125I, which is not commonly used for therapeutic purposes caused significant decrease in tumour growth from day 10 to day 42, when coupled to monoclonal antibodies directed against placental alkaline phosphatase (H7) or cytokeratins (TS1). The average growth rate was approximately 50-60% of that observed in the untreated control group after 42 days. The specific radioactivity in each organ 42 days after injection of radiolabeled monoclonal antibodies, indicated that these target antigens retain significant amounts of radiolabeled antibody in the tumours for at least 6 weeks after injection. No weight loss was seen in the animals during this experiment. By use of autoradiographic techniques, the labeled monoclonal antibodies were visualized deep in tumours in characteristic patterns representative of viable tumour cells (H7) and necrotic areas (TS1). The therapeutic approach using 125I labeled antibodies is encouraging and may offer new dimensions in radioimmunotherapy.

Adenocarcinoma↗
PubMedDate not supplied

Effects of antimicrobial drugs on the cytotoxicity of epirubicin, bleomycin, estramustine and cisplatin.

The effect of concomitant treatment with different antibiotics on the cytotoxicity of epirubicin, bleomycin, estramustine and cisplatin was studied in vitro on fibroblasts (V79) and two cancer cell lines (colon cancer HT29 and lung cancer P31). The cell lines were propagated under standard tissue culture conditions and evaluated as the number of surviving cell clones in comparison to untreated controls. Fifteen commonly used antibiotics were tested and thirteen of these were found to modify the cytotoxic effect in one or several of the combinations tested. One antibiotic agent could affect the toxicity of different cytostatics in opposite directions and there were marked differences between the cell lines tested. Only in one of the situations, the combination of bleomycin and ceftazidim, did the antibiotic cause opposite effects on the toxicity of a cytostatic when comparing fibroblasts and carcinoma cells. A most impressive observation was the pronounced increase in cisplatin-induced cytotoxicity by amphotericin B. In conclusion, the results suggest that antibiotics can interact with the cytotoxicity of antitumoral drugs but that the feature of this interaction is seemingly an erratic phenomenon. Further studies are certainly justified, especially regarding the effects of amphotericin B and its mechanisms in enhancing the cytotoxicity of cisplatin.

Amphotericin B↗
PubMedDate not supplied

The effect of estramustine on microtubuli is different from the direct action via oxygen radicals on DNA and cell membrane.

Estramustine (EM), a complex between estradiol-17 beta and nornitrogen mustard, is commonly used in the treatment of prostatic cancer. The exact mechanism of action is unknown but has previously been considered to be mediated through non-DNA targets, specifically with the mitotic spindle, and to be related to the intact EM complex. In the present study, using different cell-systems (monocyte phagocytosis transformed fibroblasts, colon cancer cells), the EM cytotoxicity was also found to involve direct interaxtion with DNA and cell membranes. The interaction with DNA was shown by a DNA precipitation assay using 3H- and 14C- thymidine, and the cell membrane damage by using 86Rb- accumulation as a sensitive marker for active potassium uptake. EM effects in the fibroblasts were inhibited by various metal chelators and radical scavengers. Involvement of free oxygen radicals was further indicated in a cell-free system with an oxygen electrode. The EM inhibition of monocyte phagocytosis was related to the engulfment, and was not at all influenced by radical scavengers. In contrast to EM, neither of its components alone, or together, affected monocyte engulfment. Finally, it was shown that the colon cancer cell-line HT-29 was resistant to both of the two suggested and separate mechanisms for EM toxicity: an interaction with the microtubuli system by the intact EM complex and a more unspecific action mediated by free-oxygen radicals.

Animals↗
PubMedDate not supplied

Effects of estramustine and its constituents on human malignant glioma cells.

Estramustine, a conjugate of estradiol-17 beta and nor-nitrogen mustard currently used in prostatic cancer, was found to exert a dose-dependent antiproliferative effect on the human malignant glioma cell lines U-251 MG and U-105 MG. At equimolar concentrations the inhibitory effects of the estramustine complex were clearly more pronounced than those of estradiol and nor-nitrogen mustard given alone or in combination. Flow cytometric analyses support the concept that estramustine cytotoxicity is mediated via separate mechanisms. The intact estramustine complex may be important for effects related to microtubule function which add to the cytotoxic potential of the alkylating component.

Cell Cycle↗
PubMedDate not supplied

Uptake, metabolism and antiproliferative effect of estramustine phosphate in human glioma cell lines.

The uptake, metabolism and antiproliferative effects of estramustine phosphate, a cytotoxic agent used in prostatic cancer, were investigated in the two human malignant glioma cell lines U-105 MG and U-251 MG. The primary metabolite estramustine had a dose-dependent inhibitory effect on cell proliferation within the concentration range 5-20 micrograms/ml. After incubation with 3H-estramustine phosphate in both cell lines, a progressive uptake of radioactivity was recorded during 24 hours. A significant metabolism of parent estramustine phosphate into estramustine and estramustine, which is a well known part of the metabolic pathway in man, was also demonstrated. In conclusion, certain cultured malignant glioma cells display significant uptake, retention and metabolism of estramustine phosphate and further studies are indicated to assess the clinical implications of these findings.

Biological Transport↗