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Journal of Medicine 1978The pyrimido-pyrimidine derivative RA 233 was found to increase circulation time and decrease metastatic settling of intravenously injected, radioisotope labeled ascites...
The pyrimido-pyrimidine derivative RA 233 was found to increase circulation time and decrease metastatic settling of intravenously injected, radioisotope labeled ascites tumor cells in mice.
Topics: Animals; Carcinoma, Ehrlich Tumor; Male; Mice; Mopidamol; Neoplasm Metastasis; Neoplastic Cells, Circulating; Platelet Aggregation; Pyrimidines
PubMed: 276567
DOI: No ID Found -
La Ricerca in Clinica E in Laboratorio 1981Recent studies suggest a relationship of platelet aggregation to metastatic spread of neoplasia. In the present experiment pentoxifylline appears to be a highly...
Recent studies suggest a relationship of platelet aggregation to metastatic spread of neoplasia. In the present experiment pentoxifylline appears to be a highly effective platelet aggregation inhibitor: a dose-response curve is apparent in monkey between 6 and 24 mg/kg i.v. Besides pentoxifylline significantly reduces metastasis rates in Wilms' tumor and neuroblastoma in rodents: 18 mg/kg significantly increase polyploid Ehrlich ascites tumor cell circulation time; on the contrary it has no effect on metastasis in the NIH renal adenocarcinoma. It is thus possible that platelet factor related blood coagulation processes play a different role in the fate of these tumor cells. This may be related to cell membrane characteristics. Phosphodiesterase inhibitors alter membrane fluidity and cell deformability of cancer cells which may pass the microcirculation easier and are less likely to settle and form metastases. Agents with both platelet aggregation inhibitory and red cell deformability increasing effect may find a place in our therapeutic armamentarium in oncology.
Topics: Adenocarcinoma; Adenosine Diphosphate; Animals; Carcinoma, Ehrlich Tumor; Female; Head and Neck Neoplasms; Humans; Kidney Neoplasms; Lung Neoplasms; Macaca; Male; Mice; Mopidamol; Neoplasm Metastasis; Pentoxifylline; Platelet Aggregation; Rats; Theobromine; Wilms Tumor
PubMed: 6324323
DOI: No ID Found -
Thrombosis Research Aug 1991
Comparative Study
Topics: Adenosine; Cardiotonic Agents; Dipyridamole; Dose-Response Relationship, Drug; Humans; Male; Mopidamol; Platelet Aggregation Inhibitors; Pyrimidines; Theophylline
PubMed: 1754999
DOI: 10.1016/0049-3848(91)90233-m -
Clinical & Experimental Metastasis 1989The pyrimido-pyrimidine analogue RA 233 has pleiotropic and differential effects on cultured tumor cell clones isolated from the 13762NF rat mammary adenocarcinoma. A...
The pyrimido-pyrimidine analogue RA 233 has pleiotropic and differential effects on cultured tumor cell clones isolated from the 13762NF rat mammary adenocarcinoma. A nonresponsive clone of low metastatic potential (MTC) was not modified in its cell fragility or invasive, adhesive or lung-colonizing properties by RA 233 treatment. In contrast, a drug-responsive clone of high metastatic potential (MTLn3) was rendered less invasive and its cell fragility was decreased with RA 233 treatment, although its adhesiveness to lung microvascular endothelial cells and subendothelial matrix was unaffected by RA 233. Lung colonization of intravenously injected MTLn3 cells in syngeneic rats was significantly increased by RA 233 treatment, whereas spontaneous metastasis from the mammary fat pad to lung sites was decreased, although this decrease was not statistically significant.
Topics: Animals; Cell Adhesion; Endothelium; Female; Mammary Neoplasms, Experimental; Mopidamol; Neoplasm Invasiveness; Neoplasm Metastasis; Pyrimidines; Rats; Rats, Inbred F344
PubMed: 2920474
DOI: 10.1007/BF01787022 -
Biochemical Pharmacology Oct 1980
Topics: Animals; Cell Division; Glycolysis; In Vitro Techniques; Leukemia L1210; Mopidamol; Pyrimidines
PubMed: 7426071
DOI: 10.1016/0006-2952(80)90089-1 -
American Journal of Clinical Oncology Jun 1989One hundred and one patients with oat (small) cell lung cancer have been treated with CAVE [Cytoxan, Adriamycin, Vincristine, and etoposide (VP-16)] chemotherapy +/-... (Clinical Trial)
Clinical Trial Comparative Study
One hundred and one patients with oat (small) cell lung cancer have been treated with CAVE [Cytoxan, Adriamycin, Vincristine, and etoposide (VP-16)] chemotherapy +/- RA233 (a platelet-inhibiting agent). There was no difference in disease-free interval, pattern of relapse, or survival between groups.
Topics: Actuarial Analysis; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Small Cell; Cyclophosphamide; Double-Blind Method; Doxorubicin; Female; Humans; Lung Neoplasms; Male; Middle Aged; Mopidamol; Podophyllotoxin; Prospective Studies; Pyrimidines; Random Allocation; Vincristine
PubMed: 2543207
DOI: 10.1097/00000421-198906000-00016 -
Journal of Medicine 1977Two pyrimido-pyrimidine derivatives (RA 233 and VK 744) were found effective aggregation inhibitors in vitro of human and monkey platelets and in vivo in stumptailed...
Two pyrimido-pyrimidine derivatives (RA 233 and VK 744) were found effective aggregation inhibitors in vitro of human and monkey platelets and in vivo in stumptailed monkeys and chimpanzees. They also inhibited thrombotic occlusion of metal screens inserted into arteriovenous shunts.
Topics: Animals; Haplorhini; Macaca; Mopidamol; Morpholines; Pan troglodytes; Platelet Aggregation; Pyrimidines
PubMed: 412904
DOI: No ID Found -
Cancer Letters 1988The pyrimido-pyrimidine derivative RA233 was found to selectively kill cultured mouse B16 melanoma cells after prolonged hypoxia. At the optimum cytotoxic concentration...
The pyrimido-pyrimidine derivative RA233 was found to selectively kill cultured mouse B16 melanoma cells after prolonged hypoxia. At the optimum cytotoxic concentration (100 microM), RA233 reduced cell clonogenicity by about 80% when administered during long-term hypoxia of 4 days. Comparable cytotoxicity was also evident when RA233 was present only during re-oxygenation following 4 days of hypoxia. RA233 treatment during both hypoxia and re-oxygenation resulted in the greatest cytotoxicity, with only about 1% of cells surviving such treatment. By contrast, the hypoxic cell sensitizer misonidazole was cytotoxic only when administered during hypoxia. RA233 appears to be a unique hypoxic cell sensitizer that kills long-term hypoxic tumor cells principally during re-oxygenation.
Topics: Animals; Cell Line; Cell Survival; Melanoma; Mice; Misonidazole; Mopidamol; Oxygen; Pyrimidines; Tumor Cells, Cultured
PubMed: 3180030
DOI: 10.1016/0304-3835(88)90249-2 -
Transactions - American Society For... 1980
Topics: Alkaline Phosphatase; Cytoplasmic Granules; Glucuronidase; Humans; In Vitro Techniques; Microscopy, Electron; Mopidamol; Neutrophils; Prostaglandins E; Pyrimidines
PubMed: 7245499
DOI: No ID Found -
Journal of Medicine 1984The antiproliferative effects of six different human interferons were examined in two human cell lines: HM7 (human melanoma cell line) and MDA-MB-231 (human breast...
The antiproliferative effects of six different human interferons were examined in two human cell lines: HM7 (human melanoma cell line) and MDA-MB-231 (human breast carcinoma cell line). A dose-response curve was developed for each interferon in which the maximum dose applied gave at least 30% growth inhibition of control values after 96-128 hours of continuous exposure. An amount of RA-233 which caused 25% growth inhibition (0.05 mg for both HM7 and MDA-MB-231 cell lines) was added to the cultures with various doses of each interferon. The inhibitory effects of RA-233 and each interferon were additive at low concentrations. In no case was a synergistic effect observed. Unlike with human fibroblast interferon, we could not show a synergistic inhibitory effect between RA 233 and any of the six different interferons on these two human epithelial tumor cell lines.
Topics: Breast Neoplasms; Cell Division; Cell Line; Drug Synergism; Humans; Interferon Type I; Interferon-gamma; Melanoma; Mopidamol; Pyrimidines
PubMed: 6436421
DOI: No ID Found