In vivo analysis of the effect of antiangiogenic drug on hepatocarcinogenesis
Project/Area Number |
18591332
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Radiation science
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Research Institution | Kanazawa University |
Principal Investigator |
MATSUI Osamu Kanazawa University, Graduate Shcool of Meclical Science, Professor (10019961)
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Project Period (FY) |
2006 – 2007
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Project Status |
Completed (Fiscal Year 2007)
|
Budget Amount *help |
¥3,880,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥480,000)
Fiscal Year 2007: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
|
Keywords | Hepatocelullar carcinoma / In vivo microscopy / VEGF / Antiangiogenic therapy / dysplastic nodule / gelatine hydrogel / thalidomide / dynamic CT / 血管新生 / 血管新生阻害剤 / 血管新生促進剤 / ゼラチンハイド、ロゲル粒子 / 肝癌 / サリドマイド / 経カテーテル治療 |
Research Abstract |
Heptocellular carcinoma (HCC) often shows multi-step hepatocarcinogenesis from dysplastic nodule (DN) to overt hypervascular HCC. Therefore, it has been considered that administration of antiangiogenic factors during early stage of hepatocarcinogenesis might prevent or delay the development of HCC. For this purpose, basic and clinical studies were carried out. To investigate the morphological change of intratumoral microvessels after administration of thalidomide (antiangiogenic agent) in occult hepatic metastases experimentally induced in rats were analyzed by fluorescent vital microscopy and immunohistochemistry. Thalidomide exerted antiangiogenic effect on the occult hepatic metastases, however, the different vascular components in the tumor vasculature demonstrated various responses to antiangiogenic therapy. The vascular changes during hepatocarcinogenesis were examined with respect to vascular endothelial growth factor (VEGF) and its receptors (Flt-1 and Flk-1), hypoxia inducible factor-1 (HIF-1), and CD34 in DNs and HCCs. The capillarized areas with increased numbers of unpaired arteries in DNs were considered to represent an early malignant transformation. Increased expression of Flk-1 and HIF-1 associated with VEGF was involved in sinusoidal capillarization and the increased numbers of unpaired arteries in these areas. To evaluate the effectiveness of gelatine hydrogel as a carrier of antiangiogenic factor for transcatheter arterial embolization therapy, bFGF (strong. angiogenic factor) contained gelatine hydrogel was directly injected into the rat liver. However, no definite effect was confirmed, and further technical improvement is necessary for this purpose. The early detection of hypervascular foci in hypovascular DNs by imaging is important to know the time of antiangiogenic therapy, and dynamic CT and/or MRI were considered to be effective in clinical practice.
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Report
(3 results)
Research Products
(78 results)
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[Journal Article] Portosystemic shunt on CT during arterial portography : prevalence in patients with and without liver cirrhosis2008
Author(s)
Terayama, N., Matsui, O., Kobayashi, S., Sanada, J., Gabata, T., Koda, W., Minami, T
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Journal Title
Abdom Imaging 33
Pages: 80-86
Description
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[Journal Article] Detection of hypervascular malignant foci in borderline lesions of hepatocellular carcinoma : comparison of dynamic multi-detector row CT, dynamic MR imaging and superparamagnetic iron oxide-enhanced MR imaging2008
Author(s)
Shinmura, R., Matsui, O., Kadoya, M., Kobayashi, S., Terayama, N., Sanada, J., Demachi, H., Gabata, T
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Journal Title
Eur Radiol. Apr 2 (Epub ahead of print)
Description
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[Journal Article] Vascular endothelial growth factor, its receptor Flk-1, and hypoxia inducible factor-lalpha are involved in malignant transformation in dysplastic nodules of the liver2007
Author(s)
Nakamura, K., Zen, Y., Sato, Y., Kozaka, K., Matsui, O., Harada, K., Nakanuma, Y
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Journal Title
Hum Pathol 38
Pages: 1532-1546
Description
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[Journal Article] A subgroup of intrahepatic cholangiocarcinoma with an infiltrating replacement growth pattern and a resemblance to reactive proliferating bile ductules : 'bile ductular carcinoma2007
Author(s)
Kozaka, K., Sasaki, M., Fujii, T., Harada, K., Zen, Y., Sato, Y., Sawada, S., Minato, H., Matsui, O., Nakanuma, Y
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Journal Title
Histopathology 51
Pages: 390-400
Description
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[Journal Article] MR imaging of hepatocellular carcinomas with biliary tumor thrombi2007
Author(s)
Gabata, T., Terayama, N., Kobayashi, S., Sanada, J., Kadoya, M., Matsui, O
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Journal Title
Abdom Imaging 32
Pages: 470-474
Description
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[Journal Article] Combined therapy of transcatheter hepatic arterial embolization with intratumoral dendritic cell infusion for hepatocellular carcinoma : clinical safety2007
Author(s)
Nakamoto, Y., Mizukoshi, E., Tsuji, H., Sakai, Y., Kitahara, M., Arai, K., Yamashita, T., Yokoyama, K., Mukaida, N., Matsushima, K., Matsui, O., Kaneko, S
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Journal Title
Clin Exp Immunol 147
Pages: 296-305
Description
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[Journal Article] Ultraselective transcatheter arterial chemoembolization with a 2-f tip microcatheter for small hepatocellular carcinomas : relationship between local tumor recurrence and visualization of the portal vein with iodized oil2007
Author(s)
Miyayama, S., Matsui, O., Yamashiro, M., Ryu, Y., Kaito, K., Ozaki, K., Takeda, T., Yoneda, N., Notsumata, K., Toya, D., Tanaka, N., Mitsui, T
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Journal Title
J Vasc Intery Radiol 18
Pages: 365-376
Description
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[Journal Article] Significance of enhanced expression of nitric oxide syntheses in splenic sinus lining cells in altered portal hemodynamics of idiopathic portal hypertension2007
Author(s)
Sato, Y., Sawada, S., Kozaka, K., Harada, K., Sasaki, M., Matsui, O., Nakanuma, Y
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Journal Title
Dig Dis Sci 52
Pages: 1987-1994
Description
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[Journal Article] Visualization of hepatic lymphatic vessels during transcatheter arterial chemoernbolization for hepatocellular carcinoma2007
Author(s)
Miyayama, S., Matsui, O., Yamashiro, M., Ryu, Y., Takata, H., Takeda, T., Aburano, H., Shigenari, N
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Journal Title
J Vasc Intery Radiol 18
Pages: 1111-1117
Description
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[Journal Article] Imaging of multistep human hepatocarcinogenesis2007
Author(s)
Matsui, O., Gabata, T., Kobayashi, S., Terayama, N., Sanada, J., Kouda, W., Kawashima, H
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Journal Title
Hepatol Res 37
Pages: 5200-205
NAID
Description
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[Journal Article] Imaging of benign hypervascular hepatocellular nodules in alcoholic liver cirrhosis : differentiation from hypervascular hepatocellular carcinoma2007
Author(s)
Kobayashi, S., Matsui, O., Kamura, T., Yamamoto, S., Yoneda, N., Gabata, T., Terayama, N., Sanada, J
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Journal Title
Comput Assist Tomogr 31
Pages: 557-563
Description
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[Journal Article] Hemodynamics of small sclerosing hepatocellular carcinoma without fibrous capsule : evaluation with single-level dynamic CT during hepatic arteriography2007
Author(s)
Kobayashi, S., Matsui, O., Gabata, T., Sanada, J., Koda, W., Minami, T., Kobayashi, T
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Journal Title
Abdom Imaging. Jul 27 (Epub ahead of print)
Description
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[Journal Article] Ultraselective transcatheter arterial chemoembolization with a 2-f tip microcatheter for small hepatocellular carcinomas : relationship between local tumor recurrence and visualization of the portal vein with iodized oil.2007
Author(s)
Miyayama S, Matsui O, Yamashiro M, Ryu Y, Kaito K, Ozaki K, Takeda T, Yoneda N, Notsumata K, Toya D, et al.
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Journal Title
J Vasc Interv Radiol. 18(3)
Pages: 365-376
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[Book] 新しい診断と治療のABC502007
Author(s)
南麻紀子、松井 修、蒲田敏文、小林 聡、南 哲弥
Total Pages
230
Publisher
最新医学社
Description
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