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Clinical & Experimental Metastasis 1983The effect of the platelet aggregation inhibitor RA233 alone or in combination with radiation was investigated on the spontaneously metastasizing B16 melanoma and on the...
The effect of the platelet aggregation inhibitor RA233 alone or in combination with radiation was investigated on the spontaneously metastasizing B16 melanoma and on the Lewis lung carcinoma. The effect of this, agent on intravenously injected cells from these tumours was also studied. When single viable 3LL or B16 melanoma cells were injected intravenously, RA233 significantly increased the number of 3LL lung colonies but decreased significantly the B16 lung colonies. RA233 alone did not influence the number of pulmonary metastases arising spontaneously from the B16 or 3LL tumours either with the primary in situ or following excision. When lungs were irradiated before implantation of the 3LL an increase in the number of metastases resulted. This increase was unaffected by RA233 administration. When the primary B16 was irradiated 14 days after implantation and excised 7 days later, a significant decrease in numbers and distribution of metastases resulted in animals treated with RA233. This was accompanied by a considerable increase in long-term survivors.
Topics: Animals; Blood Platelets; Carcinoma; Cell Line; Combined Modality Therapy; Female; Lung; Lung Neoplasms; Melanoma; Mice; Mice, Inbred C57BL; Mopidamol; Neoplasm Metastasis; Pyrimidines
PubMed: 6543684
DOI: 10.1007/BF00118472 -
American Journal of Clinical Oncology Dec 1982Considerable evidence has accumulated in recent years which implicates blood coagulation reactions in the growth and spread of malignancy. In particular, platelets may... (Clinical Trial)
Clinical Trial Review
Considerable evidence has accumulated in recent years which implicates blood coagulation reactions in the growth and spread of malignancy. In particular, platelets may accumulate on embolic tumor cells and facilitate their adhesion to the endothelium at distant sites perhaps by enhancing blood coagulation reactions. Alternatively, platelets may promote tumor cell proliferation by contributing a growth-promoting factor or through interactions mediated by prostaglandins. Inhibition of tumor growth and spread by platelet-inhibitory drugs has been demonstrated in several experimental tumor systems. Preliminary data suggest that similar effects may be seen in human malignancy. The purpose of this paper is to review relevant literature which provides the rationale for therapeutic trials of platelet-inhibitory drugs in human malignancy and to describe the experimental design for a trial involving one such drug, RA-233, in a recently established VA Cooperative Study.
Topics: Adenocarcinoma; Animals; Anticoagulants; Blood Platelets; Carcinoma, Small Cell; Clinical Trials as Topic; Colonic Neoplasms; Double-Blind Method; Humans; Lung Neoplasms; Mopidamol; Neoplasms; Neoplasms, Experimental; Pyrimidines; Random Allocation
PubMed: 6299092
DOI: 10.1097/00000421-198212000-00006 -
Cancer Letters Sep 1982The dissemination of malignant cells from a primary tumor to distant host sites appears to be influenced by blood platelets of the hemostatic system. Under conditions...
The dissemination of malignant cells from a primary tumor to distant host sites appears to be influenced by blood platelets of the hemostatic system. Under conditions that did not inhibit primary tumor growth, RA233 decreased both the incidence and frequency of spontaneous lung metastases by 66% and 69%, respectively. Although RA 233 effectively inhibited the formation of spontaneous metastases, oral administration of RA233 prior to and after the intravenous inoculation of 1 X 10(5) B16F10 murine melanoma cells failed to inhibit subsequent lung colony formation. These findings indicate that RA233 has antimetasttic activity, and that inhibition of platelet aggregation is not the sole determinant of this action.
Topics: Animals; Cell Division; Female; Lung Neoplasms; Melanoma; Mice; Mice, Inbred C57BL; Mopidamol; Neoplasms, Experimental; Platelet Aggregation; Pyrimidines
PubMed: 7151045
DOI: 10.1016/0304-3835(82)90004-0 -
Blood Jun 1982Twenty dogs with naturally occurring metastatic tumors were treated with anticoagulants (Warfarin) or platelet enzyme inhibitor drugs (dipyridamole, dipyridamole plus...
Twenty dogs with naturally occurring metastatic tumors were treated with anticoagulants (Warfarin) or platelet enzyme inhibitor drugs (dipyridamole, dipyridamole plus aspirin, RA233, sulfinpyrazone, or a combination of RA233 and sulfinpyrazone) to determine if tumor-related reductions in platelet survival and concentration could be reversed. Anticoagulation was ineffective, while platelet enzyme inhibitors were able to produce improvements in platelet survival. Of the 18 dogs with metastatic tumor treated with platelet enzyme inhibitors, only 5 (28%) showed a reduction in platelet survival during the first week of observation on therapy compared to their baseline survivals. This is significantly different than the decreases in platelet survivals observed in 8 of 10 untreated dogs (80%) with metastatic tumor observed for the same interval. Furthermore, 8 of the 18 treated dogs (44%) had platelet survivals within 2 standard deviations of normal, compared to only 1 of 10 untreated dogs. Of the 8 dogs with normal platelet survivals, 6 were treated with a combination of a phosphodiesterase inhibitor (RA233 or dipyridamole) and a cyclooxygenase inhibitor (sulfinpyrazone or aspirin). The combination of RA233 and sulfinpyrazone was the best drug program tested and resulted in normal platelet survivals in 63% and improved platelet counts in 75% of the animals treated. Thus, platelet enzyme inhibitors with different mechanisms of action may have a synergistic effect in reversing the abnormal platelet hemostasis found in a variety of spontaneously occurring canine neoplasms.
Topics: Animals; Blood Platelets; Cell Survival; Cyclooxygenase Inhibitors; Dogs; Enzyme Inhibitors; Fibrinogen; Fibrinolytic Agents; Kinetics; Mopidamol; Neoplasms; Phosphodiesterase Inhibitors; Platelet Count; Sulfinpyrazone; Warfarin
PubMed: 6805531
DOI: No ID Found -
Progress in Clinical and Biological... 1982
Topics: Animals; Female; Humans; Male; Melanoma; Mice; Mopidamol; Neoplasm Metastasis; Neoplasm Transplantation; Neoplasms; Neoplasms, Experimental; Neuroblastoma; Platelet Aggregation; Pyrimidines; Rats; Transplantation, Heterologous
PubMed: 7111312
DOI: No ID Found -
Progress in Clinical and Biological... 1982
Topics: Animals; Blood Platelets; Female; Humans; Male; Mice; Mopidamol; Neoplasm Metastasis; Neoplasm Transplantation; Neoplasms; Neoplasms, Experimental; Neoplastic Cells, Circulating; Pentoxifylline; Platelet Aggregation; Pyrimidines; Rats; Transplantation, Heterologous
PubMed: 7111311
DOI: No ID Found -
Annales Chirurgiae Et Gynaecologiae 1982
Review
Topics: Animals; Antineoplastic Agents; Blood Platelets; Carcinoma 256, Walker; Cyclic AMP; Head and Neck Neoplasms; Humans; Lung Neoplasms; Lymphoma; Male; Mice; Mopidamol; Neoplasm Metastasis; Neoplasm Recurrence, Local; Neoplasm Transplantation; Neuraminidase; Platelet Aggregation; Rabbits; Rats; Sarcoma; Vasodilator Agents
PubMed: 6287902
DOI: No ID Found -
Archives of Neurology Jun 1981In this study of the function of platelets after CNS injury, platelets were treated with serotonin labeled with radioactive carbon (14C) in animals subjected to a...
In this study of the function of platelets after CNS injury, platelets were treated with serotonin labeled with radioactive carbon (14C) in animals subjected to a freezing lesion of the cerebrum. The distribution of platelet serotonin was measured by counting the specific activity of 14C-labeled serotonin in tissue and by autoradiography. Some of the animals were treated with RA-233, which inhibits the formation of platelet plugs after endothelial damage and the release of serotonin from platelets. Platelet serotonin accumulated near the surface of the cortex at the site of injury in all animals. More cerebral edema developed in animals treated with the platelet inhibitor than in untreated animals, probably because platelet aggregates were inhibited from forming and were not available to plug leaks in the traumatized vessels. Serotonin did not appear to facilitate the spread of edema.
Topics: Animals; Blood Platelets; Brain Edema; Brain Injuries; Capillary Permeability; Cats; Dogs; Mopidamol; Serotonin
PubMed: 7236061
DOI: 10.1001/archneur.1981.00510060047006 -
Archives of Neurology May 1981In an investigation of the role of platelets in vasogenic edema in cats, direct observation of the cortex revealed that within several minutes after cold injury,...
In an investigation of the role of platelets in vasogenic edema in cats, direct observation of the cortex revealed that within several minutes after cold injury, platelet thrombi formed in small veins at the point where the veins emerged from the depths of the brain. Later, edema fluid extravasated from the veins at this same point. Pretreatment with a platelet inhibitor, RA-233, abolished the formation of platelet thrombi and remarkably enhanced the leakage of edema fluid. The microcirculation was assessed by carbon black perfusion and was found to fill better in the cats that received the platelet inhibitor. The better filling may be ascribed to a decreased number of thrombi and consequent improved blood flow in small blood vessels. We conclude that platelet aggregates play a major role in controlling the leakage of edema fluid after cold injury.
Topics: Animals; Blood Platelets; Brain; Brain Edema; Cats; Cerebrovascular Circulation; Intracranial Embolism and Thrombosis; Mopidamol; Platelet Adhesiveness; Platelet Aggregation
PubMed: 7224908
DOI: 10.1001/archneur.1981.00510050031002 -
Journal of Medicine 1981
Topics: Animals; Bencyclane; Blood Coagulation; Carcinoma 256, Walker; Depression, Chemical; Dipyridamole; Dose-Response Relationship, Drug; Humans; Mopidamol; Neoplasm Metastasis; Neoplasm Transplantation; Neoplastic Cells, Circulating; Pentoxifylline; Platelet Aggregation; Pyrimidines
PubMed: 6943264
DOI: No ID Found