Abstract | BACKGROUND & AIMS: Recent studies indicate that kringle 1-5 has a potent and specific antiangiogenic activity. Here, we investigated the antitumor effect of kringle 1-5 gene transfer on hepatocellular carcinoma in mice. METHODS: RESULTS: Proliferation of bovine capillary endothelial cells was inhibited by purified kringle 1-5 in a dose-dependent manner. Gene transfer of kringle 1-5 caused a significant reduction in vessel density with suppression of tumor growth of the 3 hepatoma cell lines and serum alpha-fetoprotein levels, prolonged the survival period, and reduced the number of intrahepatic metastases. Among the analyzed angiogenic factors, kringle 1-5 reduced angiopoietin-2 expression levels. Expression of kringle 1-5 protein was detected on hepatoma cells and hepatocytes in the liver. However, it did not alter serum alanine aminotransferase levels and body weights, suggesting kringle 1-5 lacks severe side effects. CONCLUSIONS:
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Authors | Takuji Torimura, Takato Ueno, Motoaki Kin, Eitaro Taniguchi, Toru Nakamura, Kinya Inoue, Ryuichiro Sakata, Osamu Hashimoto, Masaharu Sakamoto, Hiromasa Ohira, Ryukichi Kumashiro, Michio Sata, Hirohisa Yano, Masamichi Kojiro, Niina Veitonmaki, Yihai Cao |
Journal | Gastroenterology
(Gastroenterology)
Vol. 130
Issue 4
Pg. 1301-10
(Apr 2006)
ISSN: 0016-5085 [Print] United States |
PMID | 16618420
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- DNA, Complementary
- Alanine Transaminase
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Topics |
- Alanine Transaminase
(blood)
- Animals
- Body Weight
(drug effects)
- COS Cells
- Carcinoma, Hepatocellular
(blood, genetics, pathology, physiopathology)
- Cattle
- Cell Proliferation
(drug effects)
- Chlorocebus aethiops
- DNA, Complementary
- Endothelial Cells
(drug effects, pathology)
- Gene Transfer Techniques
- Humans
- Kringles
(genetics)
- Liver
(metabolism)
- Liver Neoplasms
(blood supply, genetics, pathology, physiopathology)
- Male
- Mice
- Mice, Inbred BALB C
- Neoplasm Metastasis
(prevention & control)
- Neovascularization, Pathologic
(pathology)
- Prognosis
- Survival Analysis
- Transfection
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