Intraperitoneal injection of adenovirus-mediated NK4 gene suppresses peritoneal dissemination of pancreatic cancer cell line AsPC-1 in nude mice

Michiyo Saimura, Eishi Nagai, Kazuhiro Mizumoto, Naoki Maehara, Hidenobu Okino, Mitsuo Katano, Kunio Matsumoto, Toshikazu Nakamura, Kou Narumi, Toshihiro Nukiwa, Masao Tanaka

研究成果: ジャーナルへの寄稿記事

57 引用 (Scopus)

抄録

NK4, composed of the N-terminal hairpin and subsequent four-kringle domains of hepatocyte growth factor (HGF), acts not only as a competitive antagonist for HGF but also as a potent angiogenesis inhibitor. This study was designed to assess a therapeutic potential of adenovirus-mediated NK4 gene transfer for disseminated pancreatic cancer cells in the peritoneal lavage of nude mice. We constructed a recombinant adenovirus NK4 (Ad-NK4), which encodes a secretable form of human NK4. In vitro migration of AsPC-1 (human pancreatic cancer cell line) was stimulated by HGF, and it was completely inhibited by Ad-NK4 transfection. Weekly intraperitoneal injections of Ad-NK4 could suppress the development of tumor nodules in a nude mouse peritoneal dissemination model. NK4 expression was detected in the disseminated nodules, liver, pancreas, spleen, and mesenterium. Immunohistochemical study of the disseminated tumors showed a remarkable decrease in microvessel density and an increase in number of apoptotic tumor cells in the Ad-NK4-treated mice. Survival of the Ad-NK4-treated mice was significantly improved. This study indicates that the intraperitoneal transduction of adenovirus- mediated NK4 gene may be a useful therapeutic modality to prevent the development of peritoneal dissemination of pancreatic cancer.

元の言語英語
ページ(範囲)799-806
ページ数8
ジャーナルCancer Gene Therapy
9
発行部数10
DOI
出版物ステータス出版済み - 1 1 2002

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Intraperitoneal Injections
Pancreatic Neoplasms
Adenoviridae
Nude Mice
Cell Line
Hepatocyte Growth Factor
Genes
Kringles
Peritoneal Lavage
Neoplasms
Angiogenesis Inhibitors
Microvessels
Transfection
Pancreas
Spleen
Survival
Liver
Therapeutics

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology
  • Cancer Research

これを引用

Intraperitoneal injection of adenovirus-mediated NK4 gene suppresses peritoneal dissemination of pancreatic cancer cell line AsPC-1 in nude mice. / Saimura, Michiyo; Nagai, Eishi; Mizumoto, Kazuhiro; Maehara, Naoki; Okino, Hidenobu; Katano, Mitsuo; Matsumoto, Kunio; Nakamura, Toshikazu; Narumi, Kou; Nukiwa, Toshihiro; Tanaka, Masao.

:: Cancer Gene Therapy, 巻 9, 番号 10, 01.01.2002, p. 799-806.

研究成果: ジャーナルへの寄稿記事

Saimura, M, Nagai, E, Mizumoto, K, Maehara, N, Okino, H, Katano, M, Matsumoto, K, Nakamura, T, Narumi, K, Nukiwa, T & Tanaka, M 2002, 'Intraperitoneal injection of adenovirus-mediated NK4 gene suppresses peritoneal dissemination of pancreatic cancer cell line AsPC-1 in nude mice', Cancer Gene Therapy, 巻. 9, 番号 10, pp. 799-806. https://doi.org/10.1038/sj.cgt.7700504
Saimura, Michiyo ; Nagai, Eishi ; Mizumoto, Kazuhiro ; Maehara, Naoki ; Okino, Hidenobu ; Katano, Mitsuo ; Matsumoto, Kunio ; Nakamura, Toshikazu ; Narumi, Kou ; Nukiwa, Toshihiro ; Tanaka, Masao. / Intraperitoneal injection of adenovirus-mediated NK4 gene suppresses peritoneal dissemination of pancreatic cancer cell line AsPC-1 in nude mice. :: Cancer Gene Therapy. 2002 ; 巻 9, 番号 10. pp. 799-806.
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abstract = "NK4, composed of the N-terminal hairpin and subsequent four-kringle domains of hepatocyte growth factor (HGF), acts not only as a competitive antagonist for HGF but also as a potent angiogenesis inhibitor. This study was designed to assess a therapeutic potential of adenovirus-mediated NK4 gene transfer for disseminated pancreatic cancer cells in the peritoneal lavage of nude mice. We constructed a recombinant adenovirus NK4 (Ad-NK4), which encodes a secretable form of human NK4. In vitro migration of AsPC-1 (human pancreatic cancer cell line) was stimulated by HGF, and it was completely inhibited by Ad-NK4 transfection. Weekly intraperitoneal injections of Ad-NK4 could suppress the development of tumor nodules in a nude mouse peritoneal dissemination model. NK4 expression was detected in the disseminated nodules, liver, pancreas, spleen, and mesenterium. Immunohistochemical study of the disseminated tumors showed a remarkable decrease in microvessel density and an increase in number of apoptotic tumor cells in the Ad-NK4-treated mice. Survival of the Ad-NK4-treated mice was significantly improved. This study indicates that the intraperitoneal transduction of adenovirus- mediated NK4 gene may be a useful therapeutic modality to prevent the development of peritoneal dissemination of pancreatic cancer.",
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AU - Okino, Hidenobu

AU - Katano, Mitsuo

AU - Matsumoto, Kunio

AU - Nakamura, Toshikazu

AU - Narumi, Kou

AU - Nukiwa, Toshihiro

AU - Tanaka, Masao

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