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Biomedical subjects

W Kalinowska

Publications and source records attributed to W Kalinowska.

6 recordsLinked to original sources

Verapamil decreases accumulation of 99Tcm-MIBI and 99Tcm-tetrofosmin in human breast cancer and soft tissue sarcoma cell lines.

99Tcm-methoxyisobutylisonitrile (99Tcm-MIBI) and 99Tcm-tetrofosmin are cationic tracers recognized by the efflux pump P-glycoprotein (Pgp). Verapamil has been shown to be a competitive inhibitor of Pgp, and was one of the first multidrug-resistant reversing agents identified. The aim of this preclinical in vitro study was to evaluate the effects of verapamil on the accumulation of 99Tcm-MIBI and 99Tcm-tetrofosmin in the human breast cancer cell lines MCF-7 and SK-BR-3 and in the human soft tissue sarcoma cell lines SW 982 and SW 1353, in comparison with respective control cells, i.e. without preincubation with verapamil. After preincubation with 10 or 100 microM of verapamil for 15 or 30 min, the 99Tcm-MIBI and 99Tcm-tetrofosmin accumulation in cells was assessed at 10, 30 and 60 min after incubation with these tracers. Addition of verapamil caused a decline in the accumulation of the two tracers at all incubation times, as compared with control cells. These effects of verapamil were neither dose- nor preincubation time-dependent in most cells. Our data indicate that verapamil is not a promising agent for increasing the sensitivity of scintigraphy with 99Tcm-MIBI or 99Tcm-tetrofosmin, or for evaluating Pgp tumour status in these types of tumours.

Adenocarcinoma↗

Uptake of 99mTc-MIBI and 99mTc-tetrofosmin into malignant versus nonmalignant breast cell lines.

UNLABELLED: The kinetics and cellular uptake of 99mTc-2-hexakis 2-methoxyiso-butyl-isonitrile (MIBI) and 99mTc-1 ,2-bis[bis(2-ethoxyethyl)phosphino]ethane (tetrofosmin) into malignant versus nonmalignant human breast cell lines were investigated and compared. METHODS: At specific intervals after incubation at 37 degrees C and 22 degrees C with 99mTc-MIBI or 99mTc-tetrofosmin, the uptake characteristics of radiotracers into human adenocarcinoma breast cell lines MCF-7 and SK-BR-3 and human breast, nontumor cell line HBL-100 were assessed. RESULTS: The uptake of 99mTc-MIBI and 99mTc-tetrofosmin was lower at an incubation temperature of 22 degrees C than that at 37 degrees C in the 3 cell lines. In MCF-7 and in SK-BR-3 cells the uptake of 99mTc-MIBI was significantly higher than the uptake of 99mTc-tetrofosmin. The uptake of 99mTc-MIBI was significantly higher into MCF-7 and SK-BR-3 cells than that into HBL-100 cells. In comparison with HBL-100 cells, uptake of 99mTc-tetrofosmin into SK-BR-3 cells was significantly higher, whereas uptake into MCF-7 cells was similar. CONCLUSION: In vitro data suggest that 99mTc-MIBI may be a better tracer than 99mTc-tetrofosmin for discrimination between malignant and nonmalignant breast disease.

Adenocarcinoma↗

Comparative 99mTc-MIBI, 99mTc-tetrofosmin and 99mTc-furifosmin uptake in human soft tissue sarcoma cell lines.

The uptake characteristics of technetium-99m hexakis-2-methoxyisobutylisonitrile (MIBI), 99mTc-tetrofosmin and 99mTc-furifosmin in human soft tissue sarcoma cell lines were investigated and compared. After 10-120 min of incubation at 37 degrees C, 32 degrees C and 22 degrees C with 99mTc-MIBI, 99mTc-tetrofosmin and 99mTc-furifosmin, the kinetics of cellular uptake of these tracers in human soft tissue sarcoma cells SW 684 (fibrosarcoma), SW 872 (liposarcoma), SW 982 (synovial sarcoma) and SW 1353 (chondrosarcoma) was assessed. The uptake of 99mTc-MIBI, 99mTc-tetrofosmin and 99mTc-furifosmin was temperature dependent. The kinetics of uptake of 99mTc-MIBI and of 99mTc-tetrofosmin was similar between fibrosarcoma and liposarcoma cells, as well as between synovial sarcoma and chondrosarcoma cells. 99mTc-furifosmin showed similar uptake kinetics in all cell lines. The uptake of 99mTc-furifosmin was, however, significantly higher in liposarcoma than in the other cells. The data indicate that the cellular uptake of 99mTc-MIBI, 99mTc-tetrofosmin and 99mTc-furifosmin is dependent on cellular metabolic activity.

Cell Survival↗

Effect of estrogen replacement therapy on natural killer cell activity in postmenopausal women.

OBJECTIVE: To evaluate the impact of menopause and estradiol substitution on natural killer cell activity. METHODS: Natural killer cell activity and antibody-dependent cellular cytotoxicity were measured in peripheral blood of 53 postmenopausal and 20 premenopausal women in an interval of 3 weeks. Postmenopausal patients were randomly assigned to receive either estradiol valerate (2 mg daily) orally (n = 18), estradiol (50 micrograms/24 h) transcutaneously (n = 18) or no substitution (n = 17), and the testing was repeated 3 weeks later. RESULTS: Natural killer cell activity but not antibody-dependent cellular cytotoxicity was significantly (P < 0.01) higher in unsubstituted postmenopausal compared to premenopausal subjects. Natural killer cell activity decreased both in orally and transcutaneously estradiol-treated patients (mean [S.D.] before vs. after 3 weeks; oral: 60.8 [9.2]% vs. 52.8 [8.2]% P < 0.01; transcutaneous: 61.5 [10.6]% vs. 54.3 [9.1]% P < 0.01; no substitution: 60.6 [10.6]% vs. 59.3 [8.9]% P > 0.1), whereas antibody-dependent cellular cytotoxicity showed no changes. The addition of 0.1 to 10 ng/ml estradiol to peripheral blood mononuclear cells of untreated postmenopausal women in vitro had no influence upon natural killer cell activity. CONCLUSION: Postmenopausal women receiving no estrogen replacement exhibited an increased natural killer cell activity which decreased during estrogen substitution.

Administration, Cutaneous↗

Natural killer cell activity and antibody-dependent cellular cytotoxicity in patients under various immunosuppressive regimens.

The influence of various modes of immunosuppression using cyclosporin A (CyA), corticosteroids (Cort), azathioprine (AZA), and antithymocyte globulin (ATG) alone or in combination with each other upon natural killer (NK) cell activity and antibody-dependent cellular cytotoxicity (ADCC) was assessed. CyA given alone did not influence either NK or ADCC activity; in contrast, the administration of Cort resulted in a significant decline (P less than 0.01) of ADCC but not of NK activity (P greater than 0.1). The combination of the two drugs led to a significant impairment of NK activity (P less than 0.01). The combination of AZA and Cort was found to produce an even more pronounced reduction in NK activity compared to both healthy controls (P less than 0.001) as well as patients from the CyA + Cort group (P less than 0.001). A similar decrease was found also after the addition of ATG to CyA + Cort (P less than 0.001, compared both with patients on CyA + Cort and with controls). In these instances, ADCC showed an overall similar pattern. We conclude that the administration of either CyA or Cort does not influence NK activity, while the combination of CyA with Cort and of AZA with Cort leads to a decrease in both NK and ADCC activities. The monotherapy with Cort only leads to a reduction of ADCC. These findings may explain the higher incidence of malignancies in patients undergoing combined immunosuppressive treatment.

Antibody-Dependent Cell Cytotoxicity↗