Analysis for roles of thrombosis-inducing factor in murine melanoma pulmonary metastases
| Project/Area Number |
04670471
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
MURANISHI Hisakazu (1993) Kyushu University, Medicine Research Associate, 医学部, 助手 (90210054)
宮崎 正之 (1992) 九州大学, 医学部, 助手 (60167674)
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| Co-Investigator(Kenkyū-buntansha) |
中西 洋一 九州大学, 医学部, 助手 (20172356)
村西 寿一 九州大学, 医学部, 助手 (90210054)
林 真一郎 九州大学, 医学部, 助手 (50211488)
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| Project Period (FY) |
1992 – 1993
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| Project Status |
Completed (Fiscal Year 1993)
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| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1993: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1992: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | thrombosis-inducing factor / hypercoagulability / experimental metastatic model |
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| Research Abstract |
A correlation exists between hemostatic abnormalities and malignancy. Thrombosis-inducing factor (TIF) is one such factor associated with hypercoagulability in patients with malignancy. Because incidence of TIF in the serum is high in patients with advanced lung cancer, the effects of TIF on experimental murine melanoma metastases to the lung were examined. TIF-positive serum increased the incidence of B16F1 pulmonary metastases significantly (3.98 times control). This enhancing effect was also found with B16F10 cells. Anti-TIF antibodies and heparin blocked this effect. Mice injected with B16F1 alone showed 3.8(〕SY.+-.〔)0.9 metastatic foci per lung. TIF-treated mice showed 61.0(〕SY.+-.〔)12.8 metastases per lung(p<0.01). The number of pulmonary metastases in mice injected with anti-QG56 antiserum-treated TIF-positive decreased significantly from that of mice injected with non-treated TIF(21.3(〕SY.+-.〔)4.5, p<0.05), to the level of mice injected with TIF-negative serum(22.3(〕SY.+-.〔)8.2, NS). TIF caused the increase in pulmonary metastases without affecting peripheral platelet counts, in dicating that the enhacing effect of TIF on experimental metastases was not a platelet-dependent phenomenon. Because residual thrombi activity in the serum might cause fibrin thrombi in vivo, the thrombin activity in the human serum, either TIF-positive or negative, was mixed with bovine fibrinogen at 37ﾟC in the presence of CaCl_2, fibrin formation was significantly delayd (clotting time > 5 minute), and there was no differnce between the thrombin time of TIF-positive and TIF-negative serum (16.2(〕SY.+-.〔)2.4 and 16.1(〕SY.+-.〔)2.8 min., respectively). More than 2U/ml thrombin was required to make a fibrin clot within 5 minutes. There was no correlation between the thrombin level in the serum and the number of metastatic foci induced by the corresponding serum. In addition, an intravenous injection of 15U of thrombin was required to induce TIF-like activity in vivo. This effe
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Research Products
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