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11. |
Vitamin K-Dependent Procoagulant in Cancer Cells: A Potential Target for the Antimetastatic Effect of Warfarin? |
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Pathophysiology of Haemostasis and Thrombosis,
Volume 16,
Issue 3-4,
1986,
Page 288-294
Maria Benedetta Donati,
Maria Carla Roncaglioni,
Anna Falanga,
Bruno Casali,
Nicola Semeraro,
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摘要:
Anticoagulants of the coumarin type have long been reported to inhibit metastasis growth in experimental animals; however, the mechanisms of such effects has not been clarified. Systemic anticoagulation per se does not appear to account completely for such metastasis growth depression. More recent information gathered on a cell procoagulant activity, which is vitamin K-dependent, could probably supply a fresh insight into this problem. Indeed, vitamin K deficiency induced either dietarily or pharmacologically by warfarin, does inhibit the activity of a cysteine protease with direct factor-X-activating properties. This protease is only present in warfarin-sensitive tumors. The correlation of this activity with cancer cell invasiveness is supported by experimental data in metastatic variants and, lately, also by the observation of markedly higher cancer procoagulant activity in extracts from metastases than from primary human melanomas.
ISSN:1424-8832
DOI:10.1159/000215300
出版商:S. Karger AG
年代:1986
数据来源: Karger
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12. |
γ-Glutamyl Carboxylase Activity in Experimental Tumor Tissues: A Biochemical Basis for Vitamin K Dependence of Cancer Procoagulant |
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Pathophysiology of Haemostasis and Thrombosis,
Volume 16,
Issue 3-4,
1986,
Page 295-299
Maria Carla Roncaglioni,
Anna Paola Bolognese Dalessandro,
Bruno Casali,
Cees Vermeer,
Maria Benedetta Donati,
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PDF (1680KB)
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摘要:
Rabbit V2 carcinoma tissues have been described to possess a procoagulant activity with specific characteristics; this material has been purified and identified as a cysteine proteinase able to directly activate coagulation factor X. We have shown here that the procoagulant activity of V2 carcinoma extracts is depressed in warfarin-treated animals, thus suggesting that cancer procoagulant could represent a new vitamin K-dependent protein. The biochemical basis for this effect is offered by the identification of γ-glutamyl carboxylase in the microsomal fraction of tumor tissues. The V2 carcinoma has a carboxylase activity which is increased in warfarin-treated animals. An endogenous substrate of tumor carboxylase, the nature of which has not been identified, has been found 5-fold increased in warfarin-treated animals. The presence of γ-glutamyl carboxylase was also described in several murine tumors including both carcinomas and fibrosarcomas. It is worth mentioning that all the tumors tested produce a procoagulant with the peculiar characteristics of that described in V2 carcinoma. It is conceivable that cancer procoagulant could represent at least one of the substrates for γ-glutamyl carboxylase in these experimental tumor tissu
ISSN:1424-8832
DOI:10.1159/000215301
出版商:S. Karger AG
年代:1986
数据来源: Karger
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13. |
Basis for Selection of Anticoagulant Drugs for Therapeutic Trials in Human Malignancy |
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Pathophysiology of Haemostasis and Thrombosis,
Volume 16,
Issue 3-4,
1986,
Page 300-320
Leo R. Zacharski,
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PDF (4090KB)
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摘要:
Evidence indicates that progression of the Lewis lung carcinoma in mice and small cell carcinoma of the lung in humans is retarded by warfarin administration. This suggests that vitamin K-dependent pathways are of importance in the pathogenesis of these tumors. Available data were reviewed for these tumor types in an attempt to explore mechanisms and to gain insights that might guide the selection of other coagulation-reactive drugs for testing in future controlled clinical trials in small cell carcinoma of the lung. While many differences exist between the Lewis lung tumor and small cell carcinoma of the lung, both are rapidly growing malignancies of pulmonary origin that metastasize early to kill the host after a short time. Both are favorably influenced by combination chemotherapy and radiation therapy as well as anticoagulant treatment. Peripheral blood changes indicative of disseminated intravascular coagulation occur in each of these tumor types, and tumor cells from both are capable of interacting with the coagulation mechanism. While many details concerning the host-tumor interaction remain to be elucidated, the considerable and diverse information available for these tumor types provides a secure base for future investigation. It is postulated that certain drugs in addition to warfarin might reasonably be studied in controlled clinical trials of small cell carcinoma of the lung and that drugs other than warfarin might be effective for tumor types that are not responsive to this agent.
ISSN:1424-8832
DOI:10.1159/000215302
出版商:S. Karger AG
年代:1986
数据来源: Karger
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