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Journal of Cancer Research and Clinical Oncology

Erschienen in:

01.08.2010 | Original Paper

Recombinant human endostatin improves anti-tumor efficacy of paclitaxel by normalizing tumor vasculature in Lewis lung carcinoma

verfasst von: Guichun Huang, Longbang Chen

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 8/2010

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Abstract

Purpose

Normalization of the tumor vasculature and microenvironment by several angiogenesis inhibitors has been reported. Given that recombinant human endostatin (rh-endostatin) is also an endogenous angiogenesis inhibitor, a comprehensive evaluation of the effects of rh-endostatin on tumor vasculature and microenvironment and chemotherapy sensitivity would be favorable.

Methods

Multiple treatment schedules of the combination of rh-endostatin and paclitaxel were tested in Lewis lung carcinoma. Further, we monitored microvascular density, tumor hypoxic fraction, and collagen covered tumor vessels at three different time points following the treatment of rh-endostatin, as well as the transcription of angiogenesis related factors (vascular endothelial growth factor-A and thrombospondin-1) and vasculature markers (regulator of G-protein signaling 5 and platelet/endothelial cell adhesion molecule-1).

Results

The anti-tumor efficacy of paclitaxel was significantly improved 7 days after the treatment of rh-endostatin. Tumor microvascular density was decreased by rh-endostatin, although it became even higher 7 days after termination of rh-endostatin. Non-necrotic hypoxic fraction was significantly reduced 7 days after treatment of rh-endostatin, accompanied with increased collagen covered tumor vessels and coverage of pericytes around endothelial cells. Rh-endostatin could transiently upregulate the transcription of thrombospondin-1 and modulate the imbalance between vascular endothelial growth factor-A and thrombospondin-1.

Conclusion

Rh-endostatin could normalize the tumor vasculature and microenvironment in Lewis lung carcinoma probably via modulation of the balance between vascular endothelial growth factor-A and thrombospondin-1. During the time of vascular normalization, paclitaxel treatment was found to have maximal effect on tumor growth delay.

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Titel: Recombinant human endostatin improves anti-tumor efficacy of paclitaxel by normalizing tumor vasculature in Lewis lung carcinoma
verfasst von: Guichun Huang
Longbang Chen
Publikationsdatum: 01.08.2010
Verlag: Springer-Verlag
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 8/2010
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-010-0770-6

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Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Recombinant human endostatin improves anti-tumor efficacy of paclitaxel by normalizing tumor vasculature in Lewis lung carcinoma

Abstract

Purpose

Methods

Results

Conclusion

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ICI-Therapie in der Schwangerschaft wird gut toleriert

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Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusion

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