Anticancer research
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Anticancer research · May 1996
Comparative StudyPharmacokinetics of a new platinum compound, cis-(glycolato-O,O) [(4R,5R)-4,5-bis(aminomethyl)-1,3-dioxolane-2-spiro-1'-cyclohexane]plat inum (II) in dogs.
A pharmacokinetic study on cis-(glycolato-O,O)/ (4R,5R)-4,5-bis(aminomethyl)-1,3-dioxolane-2-spiro-1'- cyclohexane]platinum(II) (SKI 2032R) was performed in dogs. A single dose of 2.0 mg/kg of SKI 2032R was administered i.v. bolus to three beagle dogs. ⋯ The mean area under the concentration-time curve (AUC0 --> infinity) determined for ultrafiltrable platinum derived from SKI 2032R, as an active component, was 2.36 +/- 0.23 micrograms. h/ml (mean +/- S. D.), with an initial half-life of 0.23 +/- 0.20 hour, a terminal half-life of 1.32 +/- 0.49 hour, a total clearance of 14.17 +/- 1.50 ml/min/kg, and a steady-state volume of distribution of 1.21 +/- 0.24 l/kg.
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Anticancer research · Mar 1996
Clinical course of human epithelial-type malignant pleural mesothelioma replicated in an orthotopic-transplant nude mouse model.
Malignant pleural mesothelioma is an aggressive tumor that is essentially unresponsive to standard medical and surgical therapies. Little is actually known about its biologic response to therapeutic interventions, in part because of a lack of a "patient-like" animal tumor model. Most experimental models thus far have been derived from inhalation or inoculation of asbestos fibers into animal subjects or by subcutaneous transplantation of human mesothelial cell lines into nude mice. ⋯ Histologic findings and the immunohistochemical profile were similar to those demonstrated on examination of thoracoscopic parietal pleural biopsy specimens and post-mortem examination of the original patient's tumor. This "patient-like" nude mouse model of epithelial-type malignant pleural mesothelioma, phenotypically similar to the original human tumor, should facilitate future investigation of tumorigenesis and metastatic potential of this neoplasm. The model should serve as a basis for assessing the impact of experimental and existing therapy on malignant mesothelioma.
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Anticancer research · Mar 1996
Treatment of advanced pancreatic cancer with mistletoe: results of a pilot trial.
Pancreatic cancer is a devastating disease with poor prognosis. It is characterized by its unresponsiveness to chemo- and/or radiotherapy. Therefore, many patients demand alternative drug therapy such as mistletoe treatment. ⋯ All except two patients claimed that mistletoe had a positive effect on their quality of life, with an obvious decline only during the last weeks of life. These results indicate that mistletoe is not able to significantly influence tumor growth in advanced pancreatic carcinomas. However, mistletoe treatment can stabilize quality of life, and therefore may help patients to maintain adequate life quality in their few remaining months.
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Anticancer research · Jan 1996
Comparative StudyNovel trans platinum complexes: comparative in vitro and in vivo activity against platinum-sensitive and resistant murine tumours.
Two pairs of cis/trans platinum complexes, JM118 (cis-ammine(cyclohexylamine) dichloro platinum(II)) and its trans counterpart, JM334 and JM149 (cis-ammine(cyclohexylamine) dichloro-dihydroxo platinum(IV)) and its trans counterpart JM335 have been evaluated (both in vitro and in vivo) against two murine tumour models of historical importance in the discovery of novel platinum drugs; the ADJ/PC6 plasmacytoma and the L1210 leukaemia and sublines selected for resistance to platinum drugs. In vitro, results showed that the trans complexes induced comparable growth inhibitory properties to those observed for cisplatin and their respective cis isomers. Moreover, retention of activity was observed in a series of 5 acquired platinum drug (cisplatin, carboplatin, iproplatin, tetraplatin and JM149)-resistant L1210 sublines whereas at least partial cross-resistance was observed to the cis isomer JM149 in the acquired carboplatin and iproplatin-resistant lines (in addition to being 11-fold resistant in the line selected for resistance to JM149 itself). ⋯ Interestingly, the trans platinum(II) counterpart of JM335(JM334) was inactive in vivo. These data indicate that the trans platinum(IV) complex JM335 possess several in vitro growth inhibitory- and in vivo antitumour properties which are distinct from those observed for cisplatin (or its cis isomer). Thus, JM335 contravenes the original structure-activity rules determined for platinum-containing compounds and, because of its level of activity against cisplatin-resistant tumours, establishes the complex as of interest in the search for new platinum drugs active against cisplatin-resistant disease.
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Anticancer research · Jan 1996
Effect of paclitaxel and Cremophor EL on mast cell histamine secretion and their interaction with adriamycin.
The effect of paclitaxel and of its solvent Cremophor EL, a polyoxyethylated castor oil on histamine release in rat peritoneal mast cells has been tested. Paclitaxel dissolved in Cremophor EL/ethanol and Cremophor EL alone induced a moderate histamine release; this secretory activity is provoked by the solvent Cremophor EL but is so scanty that it seems most unlikely to be responsible of the severe hypersensitivity reactions frequently caused by this drug. ⋯ This is an interesting observation since it has been suggested that anthracycline-induced histamine release is involved in the pathogenesis of the cardiotoxicity caused by these drugs. Low concentrations of paclitaxel in Cremophor EL and Cremophor EL alone inhibited adriamycin uptake into the granules of mast cells, a process mediated by an active transport system, recently identified with the P-170 glycoprotein pump.