Combined Effect Of Cisplatin Research Articles

P2.87. Combined effect of cisplatin and herpes simplex virus on oral cancer cells

P2.87. Combined effect of cisplatin and herpes simplex virus on oral cancer cells

The Combined Effect of Ultrasound Exposure and Cisplatin on Human Ovarian Carcinoma Cells A2780

This article deals with an in vitro study of the effect of cisplatin and low intensity ultrasound exposure on the viability of human ovarial carcinoma cells A2780. The effect on the viability of 103 cell experimental group samples under the influence of separate and combined cisplatin and ultrasound far field exposure was studied. Viable cells in individual experimental groups were followed at time intervals of 0, 24, 48 and 72 hours following treatment. Another objective of the study was to investigate the effect of the experimental protocol on the combined effect of cisplatin and ultrasound exposure. The effect of the concurrent application of cisplatin and ultrasound exposure was compared with that in which cisplatin was added to the cell suspension after ultrasound exposure. The results of this work confirmed the cytotoxicity of cisplatin and possible stimulation of cancer cells by low intensity ultrasound. However, it was found that ultrasound exposure enhances the action of cisplatin on the viability of A2780 cells and that the effect is dependent on the experimental protocol. In this case the concurrent application of cisplatin and ultrasound was found to be more effective (P < 0.05).

Combined effect of cisplatin and lymphokine-activated killer cells on A549 cells of non-small cell lung cancer

We studied the ability of lymphokine-activated killer cells to lyse A549 human non-small cell lung cancer cells after preincubation with cisplatin. Lymphokine-activated killer cells obtained after incubation of human blood lymphocytes with interleukin-2 were characterized by high expression of natural killer cell antigens and activation molecules. Lymphokine-activated killer cells produced potent cytotoxic effect on intact A549 cells and lysed tumor cells survived after treatment with cisplatin in concentrations of IC50 and IC30. Cisplatin in noncytotoxic concentrations did not increase lytic activity of lymphokine-activated killer cells.

The inhibitory effect of cisplatin in combination with irradiation on lung tumor cell growth is due to induction of tumor cell apoptosis.

Chemoradiation is becoming an important method of treatment of advanced lung cancer. Although many studies have demonstrated the efficacy of chemoradiation against lung tumors, the mechanism of its effect is still poorly understood. In this study, we analyzed the combined effect of cisplatin (CDDP) and irradiation on human lung cancer cell lines (PC-9 and Lu 134A) in vitro using MTT assay and isobologram analysis. To study whether the combined effect is due to induction of tumor cell apoptosis, we further quantified the nuclear fragmentation of tumor cells by flow cytometric analysis. Our study revealed that a combination of cisplatin and irradiation had an additive inhibitory effect on both PC-9 (adenocarcinoma) and Lu 134A (small cell carcinoma) tumor cell growth. Cisplatin improved the sensitivity of tumor cells to irradiation. The use of both cisplatin and irradiation doses could be reduced without decreasing the inhibitory effect. The additive inhibitory effect was correlated positively with the levels of tumor cell nuclear fragmentation. We concluded that combination treatment with cisplatin and irradiation is effective against lung tumors, not only small cell carcinoma but also non-small cell carcinoma, and the inhibitory effect was due to induction of tumor cell apoptosis.

培養癌細胞による抗癌剤の効果を高めるための実験的研究 : KB 細胞に対するシスプラチンとカフェインおよびカルシトニンとの併用効果

培養癌細胞による抗癌剤の効果を高めるための実験的研究 : KB 細胞に対するシスプラチンとカフェインおよびカルシトニンとの併用効果

Interactions of carboplatin, cisplatin, and ionizing radiation on a human cell line of ovarian cancer

Cisplatin (CDDP) and radiotherapy are frequently used concomitantly in the treatment of various malignant conditions. Because of its toxicity, cisplatin tends to be replaced by carboplatin (CBDCA) in several indications. Available data regarding the combined effects of cisplatin and carboplatin with ionising radiation are contradictory. Various concentrations of cisplatin and carboplatin and various timing of association with radiation have been tested in vitro in a human ovarian cancer cell line. The parental cell line (AOvC-0) and a cisplatin-resistant stable subline (AOvC-CDDP/0) (De Pooter et al., Canc Res, 1991) were exposed to carboplatin (2.5, 5 and 10 M) and to CDDP (1, 2.5 and 5 M), 16 h and 4 h before and 4 h and 16 h after irradiation, respectively. Cell survival was evaluated by a classical clonogenic assay. Exposure of AOvC-0 to 5 M CBDCA and of AOvC-CDDP/0 to 10 M CBDCA, before or shortly after radiation exposure, increased cell lethality in a clear supra-additive way, with the highest DEF in the shoulder region of the survival curve and at radiation doses relevant to clinical radiotherapy. In the sensitive cell line, 5 M carboplatin resulted in an additional lethality equivalent to 4.5 Gy; in the resistant cells, 10 M carboplatin was equivalent to 3.6 Gy. Replacing carboplatin by cisplatin in an identical set-up demonstrated exclusively simple additivity (DEF = 1). These data suggest that carboplatin and cisplatin delivered at equitoxic doses interact with radiation in a different way and that, in the present set-up, only carboplatin enhanced the effects of radiation. Carboplatin might consequently be a better candidate than cisplatin in some concomitant combinations with radiotherapy.

Enhanced topoisomerase I activity and increased topoisomerase II alpha content in cisplatin-resistant cancer cell lines.

Although the combined effects of cisplatin (CDDP) and DNA topoisomerase (Topo) inhibitors have been described in recent literature, little is known about the combined effects and their biological basis in CDDP‐resistant cells. The aim of the present study was to elucidate the combined effect of CDDP and Topo inhibitors on CDDP‐resistant cells as well as to investigate the biological factors involved in the sensitivity to these anti‐cancer agents. We found synergistic actions between CDDP and SN‐38 (a Topo I inhibitor) or VP‐16 (a Topo II inhibitor) in KFr cells, a CDDP‐resistant subline of the KF epithelial ovarian carcinoma cell line, but not in the parent KF cells. We subsequently assayed Topo protein levels and enzymatic activities in two sets of CDDP‐sensitive and ‐resistant cell lines: KF and KFr, and HeLa and HeLa/CDDP. The levels of Topo I protein in the CDDP‐resistant cells did not differ from those of their parent cell lines and were unaffected by exposure to CDDP. Topo I enzymatic activity, however, was 2‐ to 4‐fold higher in the CDDP‐resistant cell lines than in their respective parent cell lines. In contrast, higher levels of Topo lice protein were observed both before and after CDDP exposure in the CDDP‐resistant cells than in their controls. However, no difference in Topo II catalytic activity was observed between the CDDP‐resistant and ‐sensitive cells.

Cytostatic and clastogenic effects of cisplatin in combination with sulphur-containing compounds

Cytostatic and clastogenic effects of cisplatin in combination with sulphur-containing compounds

In vitro investigation of a combination of two drugs, cisplatin and carboplatin, as a function of the area under the c/t curve.

The log/log relationship between the IC50 of cisplatin or carboplatin and the exposure time, determined by human tumor clonogenic assay (HTCA) and MTTAI (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay with additional incubation) using PC-14 cells, exhibited a straight line with a slope of -1, indicating that both drugs have AUC-dependent cytotoxicity (AUC, area under the c/t curve). The combined effect of cisplatin and carboplatin was estimated by the median-effect analysis using HTCA, and it was additive when the AUC ratio (AUC of free platinum from carboplatin/that from cisplatin) was low (3.2, 6.5 or 13.1 in each of PC-7, PC-9, PC-14, H-69, and K562). However, it was significantly worse at a higher AUC ratio (19.5 in PC-7, PC-9, and PC-14). The log/log relationship of each drug, determined by MTTAI using human bone marrow cells, showed that each drug exerts an AUC-dependent cytotoxicity on marrow granulocytes. When cisplatin and carboplatin were combined at an AUC ratio of 14, the therapeutic index was significantly better than that of carboplatin alone and less than that of cisplatin alone using K562, PC-9 and PC-14, indicating the usefulness of this combined therapy for tumor cells with high sensitivity to platinum compounds at this AUC ratio.

Early and late effects of cisplatin and radiation at acute and low dose rates on the mouse skin and soft tissues of the leg

The influence of radiation dose rate and drug dose on the combined effects of cisplatin (Cis-diamminedichloroplatinum (II)) and radiation on the skin and soft tissues was studied in the C3H SED mice. Localized acute-dose-rate irradiation (ADRI) at 3.345 Gy/min and continuous low-dose-rate irradiation (CLDRI) of the hind leg at 0.028 Gy/min with and without the drug was delivered using a 137Cs laboratory irradiator. Cisplatin at 6 or 11 mg/kg was given by intraperitoneal bolus injection 1 hour before ADRI or by continuous infusion during CLDRI. Acute skin reaction was scored from days 13 to 30 and late skin contraction and leg contracture were measured at days 90, 180, 270, and 360 after treatment. A marked dose-rate effect was observed for these early and late normal tissue endpoints. At a dose of 60 Gy of CLDRI, the dose rate factor (DRF = isoeffect dose at CLDRI/isoeffect dose at ADRI) was 1.82 for acute skin reaction and 1.76 for late skin contraction or leg contracture at day 270. However, there was no significant enhancement of these early and late normal tissue effects by cisplatin at 6 or 11 mg/kg at either acute or low dose rates. Thus neither drug dose nor radiation dose rate had a significant impact on the combined effects of cisplatin and radiation on the mouse skin and soft tissues of the leg.

Cisplatin-Fluorouracil Interaction in a Squamous Cell Carcinoma Xenograft

Patients with squamous cell carcinoma of the head and neck are treated with cisplatin and fluorouracil according to a schedule based on the findings of clinical studies. A similar schedule showed a supra-additive effect in the treatment of xenografted human squamous cell carcinoma of the head and neck. We sought to ascertain whether this schedule was optimal. A single intraperitoneal injection of cisplatin (7.5 mg/kg) was combined with three injections of fluorouracil given during a 24-hour period (total dose, 150 or 80 mg/kg) before, during, or after cisplatin administration. The combined effect of cisplatin and fluorouracil on tumor growth and toxic effects was schedule dependent. Consideration of both toxic effects and tumor growth inhibition, as assessed by reduction of the area under the growth curve, the optimal administration interval was found to be fluorouracil given 3 days after cisplatin administration.

The combined effect of cisplatin and furosemide on hearing function in guinea pigs

The effect of the combined administration of cisplatin and furosemide on the electrophysiological hearing thresholds and endocochlear DC potential (EP) was studied in guinea pigs. A lack of interaction was found in animals given repeated intraperitoneal injections of a low dose of cisplatin with a pharmacological dose of furosemide. An ototoxic interaction occurred when a moderately high dose of cisplatin was administered intravenously at a time when the strial function was most affected by a very high dose of furosemide. The interaction was seen both as a decreased EP and a pronounced shift of auditory thresholds. It is concluded that the stria vascularis plays a role in the ototoxic mechanism of cisplatin.

The Independent Action of Radiation and Cisplatin on the Survival or Recovery of Human Normal or Tumour Cellsin Vitroorin Vivo

Recovery from radiation- or cisplatin-induced lethal damage has been studied in euoxic normal human foetal lung fibroblasts (HFL cells) that remain viable for at least 20 days in plateau-phase culture. After a 1 hour treatment with cisplatin the half-time of recovery was about 2 days. By contrast recovery after radiation was more rapid with half-times of approximately 10 h. There was no further measurable recovery after 2 days. With either agent the recovery ratios (RR) were dose-dependent but recovery (following treatment with equitoxic doses of the two agents) was appreciably greater after cisplatin (RR approximately 123 after 40 microM for 1 h) than after radiation (RR approximately 15 after 900 cGy). When radiation (900 cGy) was combined with cisplatin (40 microM for 1 h) the cell survival, measured at 5 days or later times after the treatments, was not significantly less than that predicted by the additive, independent effects of both agents (calculated as the product of their respective effects on cell survival) irrespective of whether cisplatin was given 1 h before, during or for 1 h immediately after radiation. In euoxic, exponentially growing HFL or HeLa cells there was no evidence that combinations of cisplatin and radiation gave more than additive toxic effects in the protocols tested. The combined effects of cisplatin or carboplatin and whole-body irradiation given 45 min later, on human melanoma cells (assessed by their colony-forming abilities in vitro) growing in thymectomised mice, were essentially the same as that predicted by the additive, independent effects of the two agents.