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Clinical & Experimental Metastasis
Published in: Clinical & Experimental Metastasis 5/2017

01-06-2017 | Research Paper

Portal branch ligation does not counteract the inhibiting effect of temsirolimus on extrahepatic colorectal metastatic growth

Authors: Sebastian Senger, Jens Sperling, Barbara Oberkircher, Martin K. Schilling, Otto Kollmar, Michael D. Menger, Christian Ziemann

Published in: Clinical & Experimental Metastasis | Issue 5/2017

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Abstract

The mTor-inhibitor temsirolimus (TEM) has potent anti-tumor activities on extrahepatic colorectal metastases. Treatment of patients with advanced disease may require portal branch ligation (PBL). While PBL can induce intrahepatic tumor growth, the effect of PBL on extrahepatic metastases under TEM treatment is unknown. Therefore, we analyzed the effects of TEM treatment on extrahepatic metastases during PBL-associated liver regeneration. GFP-transfected CT26.WT colorectal cancer cells were implanted into the dorsal skinfold chamber of BALB/c-mice. Mice were randomized to four groups (n = 8). One was treated daily with TEM (1.5 mg/kg), PBS-treated animals served as controls. Another group underwent PBL of the left liver lobe and received daily TEM treatment. Animals with PBL and PBS treatment served as controls. Tumor vascularization and growth as well as tumor cell migration, proliferation and apoptosis were studied over 14 days. In non-PBL animals TEM treatment inhibited tumor cell proliferation as well as vascularization and growth of the extrahepatic metastases. PBL did not influence tumor cell engraftment, vascularization and metastatic growth. Of interest, TEM treatment significantly reduced tumor cell engraftment, neovascularization and metastatic groth also after PBL. PBL does not counteract the inhibiting effect of TEM on extrahepatic colorectal metastatic growth.
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Metadata
Title
Portal branch ligation does not counteract the inhibiting effect of temsirolimus on extrahepatic colorectal metastatic growth
Authors
Sebastian Senger
Jens Sperling
Barbara Oberkircher
Martin K. Schilling
Otto Kollmar
Michael D. Menger
Christian Ziemann
Publication date
01-06-2017
Publisher
Springer Netherlands
Published in
Clinical & Experimental Metastasis / Issue 5/2017
Print ISSN: 0262-0898
Electronic ISSN: 1573-7276
DOI
https://doi.org/10.1007/s10585-017-9852-z

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