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A combination of low-dose bevacizumab and imatinib enhances vascular normalisation without inducing extracellular matrix deposition

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A combination of low-dose bevacizumab and imatinib enhances vascular normalisation without inducing extracellular matrix deposition. / Schiffmann, L M; Brunold, M; Liwschitz, M; Goede, V; Loges, S; Wroblewski, M; Quaas, A; Alakus, H; Stippel, D; Bruns, C J; Hallek, M; Kashkar, H; Hacker, U T; Coutelle, O.

In: BRIT J CANCER, Vol. 116, No. 5, 28.02.2017, p. 600-608.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Schiffmann, LM, Brunold, M, Liwschitz, M, Goede, V, Loges, S, Wroblewski, M, Quaas, A, Alakus, H, Stippel, D, Bruns, CJ, Hallek, M, Kashkar, H, Hacker, UT & Coutelle, O 2017, 'A combination of low-dose bevacizumab and imatinib enhances vascular normalisation without inducing extracellular matrix deposition', BRIT J CANCER, vol. 116, no. 5, pp. 600-608. https://doi.org/10.1038/bjc.2017.13

APA

Schiffmann, L. M., Brunold, M., Liwschitz, M., Goede, V., Loges, S., Wroblewski, M., Quaas, A., Alakus, H., Stippel, D., Bruns, C. J., Hallek, M., Kashkar, H., Hacker, U. T., & Coutelle, O. (2017). A combination of low-dose bevacizumab and imatinib enhances vascular normalisation without inducing extracellular matrix deposition. BRIT J CANCER, 116(5), 600-608. https://doi.org/10.1038/bjc.2017.13

Vancouver

Schiffmann LM, Brunold M, Liwschitz M, Goede V, Loges S, Wroblewski M et al. A combination of low-dose bevacizumab and imatinib enhances vascular normalisation without inducing extracellular matrix deposition. BRIT J CANCER. 2017 Feb 28;116(5):600-608. https://doi.org/10.1038/bjc.2017.13

Bibtex

@article{3bed9b96a6ba49dca95798189e7007bb,
title = "A combination of low-dose bevacizumab and imatinib enhances vascular normalisation without inducing extracellular matrix deposition",
abstract = "BACKGROUND: Vascular endothelial growth factor (VEGF)-targeting drugs normalise the tumour vasculature and improve access for chemotherapy. However, excessive VEGF inhibition fails to improve clinical outcome, and successive treatment cycles lead to incremental extracellular matrix (ECM) deposition, which limits perfusion and drug delivery. We show here, that low-dose VEGF inhibition augmented with PDGF-R inhibition leads to superior vascular normalisation without incremental ECM deposition thus maintaining access for therapy.METHODS: Collagen IV expression was analysed in response to VEGF inhibition in liver metastasis of colorectal cancer (CRC) patients, in syngeneic (Panc02) and xenograft tumours of human colorectal cancer cells (LS174T). The xenograft tumours were treated with low (0.5 mg kg-1 body weight) or high (5 mg kg-1 body weight) doses of the anti-VEGF antibody bevacizumab with or without the tyrosine kinase inhibitor imatinib. Changes in tumour growth, and vascular parameters, including microvessel density, pericyte coverage, leakiness, hypoxia, perfusion, fraction of vessels with an open lumen, and type IV collagen deposition were compared.RESULTS: ECM deposition was increased after standard VEGF inhibition in patients and tumour models. In contrast, treatment with low-dose bevacizumab and imatinib produced similar growth inhibition without inducing detrimental collagen IV deposition, leading to superior vascular normalisation, reduced leakiness, improved oxygenation, more open vessels that permit perfusion and access for therapy.CONCLUSIONS: Low-dose bevacizumab augmented by imatinib selects a mature, highly normalised and well perfused tumour vasculature without inducing incremental ECM deposition that normally limits the effectiveness of VEGF targeting drugs.",
keywords = "Animals, Antineoplastic Combined Chemotherapy Protocols, Bevacizumab, Cell Line, Tumor, Collagen Type IV, Colorectal Neoplasms, Extracellular Matrix, Humans, Imatinib Mesylate, Liver Neoplasms, Mice, Treatment Outcome, Xenograft Model Antitumor Assays, Journal Article",
author = "Schiffmann, {L M} and M Brunold and M Liwschitz and V Goede and S Loges and M Wroblewski and A Quaas and H Alakus and D Stippel and Bruns, {C J} and M Hallek and H Kashkar and Hacker, {U T} and O Coutelle",
year = "2017",
month = feb,
day = "28",
doi = "10.1038/bjc.2017.13",
language = "English",
volume = "116",
pages = "600--608",
journal = "BRIT J CANCER",
issn = "0007-0920",
publisher = "NATURE PUBLISHING GROUP",
number = "5",

}

RIS

TY - JOUR

T1 - A combination of low-dose bevacizumab and imatinib enhances vascular normalisation without inducing extracellular matrix deposition

AU - Schiffmann, L M

AU - Brunold, M

AU - Liwschitz, M

AU - Goede, V

AU - Loges, S

AU - Wroblewski, M

AU - Quaas, A

AU - Alakus, H

AU - Stippel, D

AU - Bruns, C J

AU - Hallek, M

AU - Kashkar, H

AU - Hacker, U T

AU - Coutelle, O

PY - 2017/2/28

Y1 - 2017/2/28

N2 - BACKGROUND: Vascular endothelial growth factor (VEGF)-targeting drugs normalise the tumour vasculature and improve access for chemotherapy. However, excessive VEGF inhibition fails to improve clinical outcome, and successive treatment cycles lead to incremental extracellular matrix (ECM) deposition, which limits perfusion and drug delivery. We show here, that low-dose VEGF inhibition augmented with PDGF-R inhibition leads to superior vascular normalisation without incremental ECM deposition thus maintaining access for therapy.METHODS: Collagen IV expression was analysed in response to VEGF inhibition in liver metastasis of colorectal cancer (CRC) patients, in syngeneic (Panc02) and xenograft tumours of human colorectal cancer cells (LS174T). The xenograft tumours were treated with low (0.5 mg kg-1 body weight) or high (5 mg kg-1 body weight) doses of the anti-VEGF antibody bevacizumab with or without the tyrosine kinase inhibitor imatinib. Changes in tumour growth, and vascular parameters, including microvessel density, pericyte coverage, leakiness, hypoxia, perfusion, fraction of vessels with an open lumen, and type IV collagen deposition were compared.RESULTS: ECM deposition was increased after standard VEGF inhibition in patients and tumour models. In contrast, treatment with low-dose bevacizumab and imatinib produced similar growth inhibition without inducing detrimental collagen IV deposition, leading to superior vascular normalisation, reduced leakiness, improved oxygenation, more open vessels that permit perfusion and access for therapy.CONCLUSIONS: Low-dose bevacizumab augmented by imatinib selects a mature, highly normalised and well perfused tumour vasculature without inducing incremental ECM deposition that normally limits the effectiveness of VEGF targeting drugs.

AB - BACKGROUND: Vascular endothelial growth factor (VEGF)-targeting drugs normalise the tumour vasculature and improve access for chemotherapy. However, excessive VEGF inhibition fails to improve clinical outcome, and successive treatment cycles lead to incremental extracellular matrix (ECM) deposition, which limits perfusion and drug delivery. We show here, that low-dose VEGF inhibition augmented with PDGF-R inhibition leads to superior vascular normalisation without incremental ECM deposition thus maintaining access for therapy.METHODS: Collagen IV expression was analysed in response to VEGF inhibition in liver metastasis of colorectal cancer (CRC) patients, in syngeneic (Panc02) and xenograft tumours of human colorectal cancer cells (LS174T). The xenograft tumours were treated with low (0.5 mg kg-1 body weight) or high (5 mg kg-1 body weight) doses of the anti-VEGF antibody bevacizumab with or without the tyrosine kinase inhibitor imatinib. Changes in tumour growth, and vascular parameters, including microvessel density, pericyte coverage, leakiness, hypoxia, perfusion, fraction of vessels with an open lumen, and type IV collagen deposition were compared.RESULTS: ECM deposition was increased after standard VEGF inhibition in patients and tumour models. In contrast, treatment with low-dose bevacizumab and imatinib produced similar growth inhibition without inducing detrimental collagen IV deposition, leading to superior vascular normalisation, reduced leakiness, improved oxygenation, more open vessels that permit perfusion and access for therapy.CONCLUSIONS: Low-dose bevacizumab augmented by imatinib selects a mature, highly normalised and well perfused tumour vasculature without inducing incremental ECM deposition that normally limits the effectiveness of VEGF targeting drugs.

KW - Animals

KW - Antineoplastic Combined Chemotherapy Protocols

KW - Bevacizumab

KW - Cell Line, Tumor

KW - Collagen Type IV

KW - Colorectal Neoplasms

KW - Extracellular Matrix

KW - Humans

KW - Imatinib Mesylate

KW - Liver Neoplasms

KW - Mice

KW - Treatment Outcome

KW - Xenograft Model Antitumor Assays

KW - Journal Article

U2 - 10.1038/bjc.2017.13

DO - 10.1038/bjc.2017.13

M3 - SCORING: Journal article

C2 - 28141797

VL - 116

SP - 600

EP - 608

JO - BRIT J CANCER

JF - BRIT J CANCER

SN - 0007-0920

IS - 5

ER -