| Project/Area Number |
14360183
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Applied veterinary science
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| Research Institution | RAKUNO GAKUEN UNIVERSITY (2004)
Hokkaido University (2002-2003) |
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Principal Investigator |
KADOSAWA Tsuyoshi Rkuno Gakuen Univ., School of Veterinary Medicine, Professor, 獣医学部, 教授 (70214418)
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| Co-Investigator(Kenkyū-buntansha) |
TKIGUCHI Mitsuyoshi Rkuno Gakuen Univ., School of Veterinary Medicine, Professor, 獣医学部, 教授 (70261336)
OCHIAI Kenji Hokkaido Univ., Graduate School of Veterinary Medicine, Associate Professor, 大学院・獣医学研究科, 助教授 (80214162)
KASAOKA Tatsuhiko Pharmaceutical Research Laboratories, Novartis Pharma K. K., Researcher, 主任研究員
OOIZUMI Iwao Pharmaceutical Research Laboratories, Chugai Pharmaceutical Co. Ltd., Researcher, 研究員
KUSAKA Masami Pharmaceutical Research Laboratories, Takeda Chemical Industries, Ltd., Research Head, 主席研究員
日下 雅実 武田薬品株式会社, 主席研究員
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥10,400,000 (Direct Cost: ¥10,400,000)
Fiscal Year 2004: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2003: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2002: ¥3,300,000 (Direct Cost: ¥3,300,000)
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| Keywords | Tumor / Tumor Dormancy Therapy / Differentiation / Anti-angiogenesis / Dog / 臨床試験 / 腫瘍血管 |
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| Research Abstract |
A clinical evaluation of the novel angiogenesis inhibitor TNP 470, Thalidomide and differentiation agent OCT (22-oxa-calcitriol) for tumor dormancy was performed. Dogs with advanced spontaneous malignant tumors and their owners' consent to a pilot study were eligible
TNP 470, a dose of 12.5-223mg/m^2., was administered to 47 dogs subcutaneously or intravenously 1-3 times per week. Lameness or shivering were encountered in 9 dogs. Seizure was shown in 4 dogs, and bleeding, anorexia and vomiting were in a dog, respectively. Thalidomide, daily oral dose of 5.0-20mg/kg B.W., was administered to 23 dogs. Lameness, sedation or softer feces were observed in 6 dogs. Though there was a tendency to increase of these clinical signs in higher doses, most were induced by a sleeping effect in itself. OCT, daily oral dose of 0.03-0.12 Lt g/kg B.W. was administered to 31 dogs. In 21 dogs receiving over 2 weeks, 7 dogs showed hypercalcemia. Hypercalcemia resolved, followed by a 7-day rest period. In each drugs, side effects and changes in blood chemical analysis were not serious.
Evaluations of anti-tumor effects, such as inhibition of tumor growth and metastasis, were difficult without a control group. But primary or metastatic lesions shrank by these agents in a few dogs. A small number of dogs with highly metastasizing tumors such as osteosarcoma survived for a long time without progressive disease.
In this clinical study, dogs with advanced malignant tumors tolerated well to TNP-470, Thalidomide and OCT, and some encouraging anti-tumor effects were shown. Further studies of tumor dormancy therapy by anti-angiogenesis and differentiation agents are warranted.
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