Anticancer research
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Anticancer research · Nov 1993
The effect of local anaesthetics on the thermal sensitivity of HTC cells.
Local anaesthetics caused death of HTC cells, and the order of toxicity (dibucaine > tetracaine > procaine) correlated with their oil:water partition coefficients. Cytotoxic effects of hyperthermia were enhanced by subtoxic levels of anaesthetics and again, their potency was related to the oil:water partition coefficients. ⋯ At 43 degrees C, plasma membrane fluidity was increased by dibucaine but not by tetracaine or procaine. The results suggest that fluidisation of the hydrophobic core of the membrane may contribute to anaesthetic potentiation of heat cell death.
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Anticancer research · Nov 1992
Comparative StudyCytostatic activity of cisplatin in the presence of WR2721 and its thiol metabolite WR1065 in OVCAR-3 human ovarian cancer cells as compared to V79 fibroblasts.
The effect of the modulating agent WR2721 (S-2-(3-aminopropylamino)ethylphosphorothioic acid, ethiofos) and its active thiol metabolite WR1065 on the cytostatic effect of cisplatin was investigated in a human ovarian cancer cell line OVCAR-3 and compared to that in V79 fibroblasts. WR1065 protected both OVCAR-3 and V79 cells against the cytostatic effect of cisplatin when incubated together with (co-incubation) or 15 min prior to (pre-incubation) the platinum drug. A dose-related effect up to complete protection was obtained when cells were coincubated with WR1065. ⋯ The parent drug WR2721, up to a concentration of 0.01 M, did not protect OVCAR-3 and V79 cells when co-incubated with cisplatin. These results support the conclusions: a) that WR1065, and not the parent drug WR2721, is the protective species entering the cells, b) that prevention of damage is the main mechanism of protection and c) that tissues are expected to be protected by WR2721 only if WR1065 is formed and taken up by these tissues. Therefore, the preferential formation and uptake of WR1065 by non-tumour tissues is essential for a successful combination of WR2721 with platinum chemotherapy.
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Anticancer research · Sep 1992
Proliferative effect of dexamethasone on a human glioblastoma cell line (HU 197) is mediated by glucocorticoid receptors.
The relationship between Dexamethasone proliferative activity and the presence of glucocorticoid receptors was studied on a human glioblastoma cell line (HU 197). For this purpose, the 17 beta-Carboxamide steroid DXB, a glucocorticoid antagonist that competes with Dexamethasone for binding to the intracellular glucocorticoid receptor but does not trigger the glucocorticoid effect, was used. Concurrent treatments with Dexamethasone and DXB caused an inhibition of the proliferative effect obtained by Dexamethasone. The results obtained demonstrated that the Dexamethasone activity on cell proliferation is a specific receptor-mediated effect.
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Anticancer research · Jul 1992
Differential effects of the spermine analog, N1, N12-bis(ethyl)-spermine, on polyamine metabolism and cell growth in human melanoma cell lines and melanocytes.
We have previously found that in one of two human melanoma cell lines, potent increase in the polyamine catabolizing enzyme, spermidine/spermine N1-acetyltransferase (SSAT), correlate with growth sensitivity to the spermine analog, N1, N12-bis(ethyl) spermine (BESPM). Herein, we examine the generality of this SSAT response among seven human melanoma cell lines (LOX, SH-1, STO-1, HO, PANUT-3, MALME-3 and Ebey) and normal melanocytes and further evaluate its possible correlation with growth sensitivity. Following treatment with 10 microM BESPM for 48 hr, SSAT activity among the various cell lines increased from basal levels of 20-90 pmol/min/mg to levels ranging from 170 to 30,470 pmol/min/mg. ⋯ The polyamine biosynthetic enzyme activities, ornithine and S-adenosylmethionine decarboxylase, were similarly suppressed in all cell lines, presumably via analog activation of inherent regulatory mechanisms. Polyamine pool reduction occurred to a greater extent than predicted in cell lines where SSAT was increased to greater than 2500 pmol/min/mg suggesting a possible role for the enzyme in enhancing polyamine excretion and/or catabolism. The occurrence of potent SSAT induction among several human melanoma cell lines and the growth sensitivity of these same lines to BESPM suggests that the enzyme response may represent a determinant of drug action in this particular malignancy.
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Anticancer research · May 1992
Sex steroid receptors, S-phase fraction and DNA ploidy as determinants of the risk of relapse and death of female breast cancer.
S phase fraction (SPF) and DNA ploidy were related to disease outcome by a separate analysis of sex steroid receptor positive and negative tumours in a series of 232 patients with breast carcinoma followed-up for over 8 years in our clinic. SPF was significantly higher in receptor-negative tumours than in receptor-positive ones (p = 0.037). SPF predicted recurrence only in ER+ or PR+ patients (p = 0.02-0.003). ⋯ To conclude, the proliferation rate as measured by S phase fraction by FCM is a highly significant prognostic factor in breast cancer. The prognostic value of S phase fraction is confined to steroid receptor-positive tumours, whereas in receptor-negative tumours SPF has no predictive value. The results thus suggest that all women with steroid receptor-negative breast tumours and those receptor-positive tumours with an SPF higher than 9% should be subjected to postoperative adjuvant chemotherapy immediately.