A Role of Cytokines in OK-432 Injection Therapy for Cystic Lymphangioma: An Approach to the Mechanism

Akihiro Fujino, Yoichiro Moriya, Yasuhide Morikawa, Ken Hoshino, Toshihiko Watanabe, Naoki Shimojima, Masaki Kitajima

Research output: Contribution to journalArticle

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Abstract

Purpose: This study examines cytokine levels of aspirates from cystic lymphangiomas after injection of OK-432 and over the course of several weeks to better understand the process of tumor regression. Methods: Fluids aspirated from lymphangioma cysts of 3 patients were collected sequentially before and after OK-432 injection. Mononuclear cells (MNCs) were separated and cultured with or without OK-432. Vascular endothelial growth factor (VEGF), soluble VEGF receptor 1 (sVEGFR1), sVEGFR2, transforming growth factor beta-1 (TGF-β1), interleukin (IL)-6, IL-8, IL-12+p40, tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) levels in the supernatants of the aspirates and the culture supernatants of MNCs were then measured by ELISA. Results: The aspirates exhibited a marked elevation in IL-6, IL-8, VEGF, and TGF-β1 levels for a few weeks after the OK-432 injection. IL-6, IL-8, IL-12+p40, TNF-α, and IFN-γ levels were elevated in the culture supernatants of the MNC cultured with OK-432 for up to 9 days. All the tumors regressed significantly, with sclerotic change, within 3 months after OK-432 Injection. Conclusions: Cytokine production is maintained for a few weeks after OK-432 injection. Fibrotic changes may be another main mechanism in tumor regression in addition to cytotoxic effects on lymphangioma cells. A close relationship between cytokines from intracystic cells and lymphangioma cells is suggested.

Original languageEnglish
Pages (from-to)1806-1809
Number of pages4
JournalJournal of Pediatric Surgery
Volume38
Issue number12
DOIs
Publication statusPublished - 2003 Dec

Fingerprint

Picibanil
Cystic Lymphangioma
Cytokines
Injections
Lymphangioma
Interleukin-8
Interleukin-6
Interleukin-12
Transforming Growth Factor beta
Vascular Endothelial Growth Factor A
Therapeutics
Tumor Necrosis Factor-alpha
Vascular Endothelial Growth Factor Receptor-1
Neoplasms
Interferon-alpha
Interferon-gamma
Cysts
Cultured Cells
Enzyme-Linked Immunosorbent Assay

Keywords

  • Cytotoxicity
  • Fibrotic change
  • Lymphangioma
  • OK-432
  • Transforming growth factor beta-1
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Surgery

Cite this

Fujino, A., Moriya, Y., Morikawa, Y., Hoshino, K., Watanabe, T., Shimojima, N., & Kitajima, M. (2003). A Role of Cytokines in OK-432 Injection Therapy for Cystic Lymphangioma: An Approach to the Mechanism. Journal of Pediatric Surgery, 38(12), 1806-1809. https://doi.org/10.1016/j.jpedsurg.2003.08.041

A Role of Cytokines in OK-432 Injection Therapy for Cystic Lymphangioma : An Approach to the Mechanism. / Fujino, Akihiro; Moriya, Yoichiro; Morikawa, Yasuhide; Hoshino, Ken; Watanabe, Toshihiko; Shimojima, Naoki; Kitajima, Masaki.

In: Journal of Pediatric Surgery, Vol. 38, No. 12, 12.2003, p. 1806-1809.

Research output: Contribution to journalArticle

Fujino, A, Moriya, Y, Morikawa, Y, Hoshino, K, Watanabe, T, Shimojima, N & Kitajima, M 2003, 'A Role of Cytokines in OK-432 Injection Therapy for Cystic Lymphangioma: An Approach to the Mechanism', Journal of Pediatric Surgery, vol. 38, no. 12, pp. 1806-1809. https://doi.org/10.1016/j.jpedsurg.2003.08.041
Fujino, Akihiro ; Moriya, Yoichiro ; Morikawa, Yasuhide ; Hoshino, Ken ; Watanabe, Toshihiko ; Shimojima, Naoki ; Kitajima, Masaki. / A Role of Cytokines in OK-432 Injection Therapy for Cystic Lymphangioma : An Approach to the Mechanism. In: Journal of Pediatric Surgery. 2003 ; Vol. 38, No. 12. pp. 1806-1809.
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AU - Moriya, Yoichiro

AU - Morikawa, Yasuhide

AU - Hoshino, Ken

AU - Watanabe, Toshihiko

AU - Shimojima, Naoki

AU - Kitajima, Masaki

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N2 - Purpose: This study examines cytokine levels of aspirates from cystic lymphangiomas after injection of OK-432 and over the course of several weeks to better understand the process of tumor regression. Methods: Fluids aspirated from lymphangioma cysts of 3 patients were collected sequentially before and after OK-432 injection. Mononuclear cells (MNCs) were separated and cultured with or without OK-432. Vascular endothelial growth factor (VEGF), soluble VEGF receptor 1 (sVEGFR1), sVEGFR2, transforming growth factor beta-1 (TGF-β1), interleukin (IL)-6, IL-8, IL-12+p40, tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) levels in the supernatants of the aspirates and the culture supernatants of MNCs were then measured by ELISA. Results: The aspirates exhibited a marked elevation in IL-6, IL-8, VEGF, and TGF-β1 levels for a few weeks after the OK-432 injection. IL-6, IL-8, IL-12+p40, TNF-α, and IFN-γ levels were elevated in the culture supernatants of the MNC cultured with OK-432 for up to 9 days. All the tumors regressed significantly, with sclerotic change, within 3 months after OK-432 Injection. Conclusions: Cytokine production is maintained for a few weeks after OK-432 injection. Fibrotic changes may be another main mechanism in tumor regression in addition to cytotoxic effects on lymphangioma cells. A close relationship between cytokines from intracystic cells and lymphangioma cells is suggested.

AB - Purpose: This study examines cytokine levels of aspirates from cystic lymphangiomas after injection of OK-432 and over the course of several weeks to better understand the process of tumor regression. Methods: Fluids aspirated from lymphangioma cysts of 3 patients were collected sequentially before and after OK-432 injection. Mononuclear cells (MNCs) were separated and cultured with or without OK-432. Vascular endothelial growth factor (VEGF), soluble VEGF receptor 1 (sVEGFR1), sVEGFR2, transforming growth factor beta-1 (TGF-β1), interleukin (IL)-6, IL-8, IL-12+p40, tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) levels in the supernatants of the aspirates and the culture supernatants of MNCs were then measured by ELISA. Results: The aspirates exhibited a marked elevation in IL-6, IL-8, VEGF, and TGF-β1 levels for a few weeks after the OK-432 injection. IL-6, IL-8, IL-12+p40, TNF-α, and IFN-γ levels were elevated in the culture supernatants of the MNC cultured with OK-432 for up to 9 days. All the tumors regressed significantly, with sclerotic change, within 3 months after OK-432 Injection. Conclusions: Cytokine production is maintained for a few weeks after OK-432 injection. Fibrotic changes may be another main mechanism in tumor regression in addition to cytotoxic effects on lymphangioma cells. A close relationship between cytokines from intracystic cells and lymphangioma cells is suggested.

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KW - Fibrotic change

KW - Lymphangioma

KW - OK-432

KW - Transforming growth factor beta-1

KW - Vascular endothelial growth factor

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