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Differential vascular and transcriptional responses to anti-vascular endothelial growth factor antibody in orthotopic human pancreatic cancer xenografts

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Differential vascular and transcriptional responses to anti-vascular endothelial growth factor antibody in orthotopic human pancreatic cancer xenografts. / Bockhorn, Maximilian; Tsuzuki, Yoshikazu; Xu, Lei; Frilling, Andreja; Broelsch, Christoph E; Fukumura, Dai.

in: CLIN CANCER RES, Jahrgang 9, Nr. 11, 15.09.2003, S. 4221-6.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Bockhorn, M, Tsuzuki, Y, Xu, L, Frilling, A, Broelsch, CE & Fukumura, D 2003, 'Differential vascular and transcriptional responses to anti-vascular endothelial growth factor antibody in orthotopic human pancreatic cancer xenografts', CLIN CANCER RES, Jg. 9, Nr. 11, S. 4221-6.

APA

Bockhorn, M., Tsuzuki, Y., Xu, L., Frilling, A., Broelsch, C. E., & Fukumura, D. (2003). Differential vascular and transcriptional responses to anti-vascular endothelial growth factor antibody in orthotopic human pancreatic cancer xenografts. CLIN CANCER RES, 9(11), 4221-6.

Vancouver

Bockhorn M, Tsuzuki Y, Xu L, Frilling A, Broelsch CE, Fukumura D. Differential vascular and transcriptional responses to anti-vascular endothelial growth factor antibody in orthotopic human pancreatic cancer xenografts. CLIN CANCER RES. 2003 Sep 15;9(11):4221-6.

Bibtex

@article{5c6217852f1d4ab8bbcb11a0ceaf849a,
title = "Differential vascular and transcriptional responses to anti-vascular endothelial growth factor antibody in orthotopic human pancreatic cancer xenografts",
abstract = "PURPOSE: The objectives of this study were to investigate the effects of anti-vascular endothelial growth factor (VEGF) treatment on various vascular functions, gene expression, and growth of orthotopic human pancreatic cancer xenografts and thus to provide useful preclinical data for novel cancer treatments.EXPERIMENTAL DESIGN: Small pieces of a human pancreatic carcinoma, PANC-1, were implanted into the pancreas of male severe combined immunodeficient mice. The animals were treated with anti-human VEGF antibody A.4.6.1 (300 micro g, every 3 days i.p.) or a nonspecific IgG between 4 and 8 weeks after tumor implantation. Then, vascular density, diameter, permeability, and tumor growth were determined by intravital microscopy. Subsequently, tumors were harvested, and angiogenic gene expression profile was determined by a microarray kit including 96 genes involved in tumor angiogenesis.RESULTS: Anti-VEGF antibody significantly reduced angiogenesis and growth of orthotopic PANC-1 tumors. In the anti-VEGF treatment group, the vessel density was significantly smaller (67.8 +/- 10.6 cm/cm(2)) than that seen in the control group (146.7 +/- 10.0 cm/cm(2)). However, vessel diameter and permeability were not altered significantly by anti-VEGF antibody treatment. The pancreatic tumors in the treated group were significantly smaller than those in the control group. Microarray and subsequent Northern blot and semiquantitative reverse transcription-PCR analyses revealed both a decrease (fibroblast growth factor 1, transforming growth factor beta1, platelet-derived growth factor alpha, erbB2, and c-ets1,) and an increase (placenta growth factor, hypoxia-inducible factor alpha, and endoglin) in expression of angiogenesis-related genes in the PANC-1 tumors by anti-VEGF treatment.CONCLUSIONS: Anti-VEGF antibody treatment has differential effects on vessel functions as well as angiogenic gene expression and inhibitory effects on angiogenesis and growth of the orthotopic pancreatic tumor. Anti-VEGF strategy appears promising for pancreatic cancer treatment.",
keywords = "Animals, Antibodies, Base Sequence, Capillary Permeability, Cell Division, DNA Primers, Gene Expression Regulation, Neoplastic, Humans, Male, Mice, Mice, SCID, Neovascularization, Pathologic, Neutralization Tests, Oligonucleotide Array Sequence Analysis, Pancreatic Neoplasms, Reverse Transcriptase Polymerase Chain Reaction, Transcription, Genetic, Transplantation, Heterologous, Vascular Endothelial Growth Factor A",
author = "Maximilian Bockhorn and Yoshikazu Tsuzuki and Lei Xu and Andreja Frilling and Broelsch, {Christoph E} and Dai Fukumura",
year = "2003",
month = sep,
day = "15",
language = "English",
volume = "9",
pages = "4221--6",
journal = "CLIN CANCER RES",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "11",

}

RIS

TY - JOUR

T1 - Differential vascular and transcriptional responses to anti-vascular endothelial growth factor antibody in orthotopic human pancreatic cancer xenografts

AU - Bockhorn, Maximilian

AU - Tsuzuki, Yoshikazu

AU - Xu, Lei

AU - Frilling, Andreja

AU - Broelsch, Christoph E

AU - Fukumura, Dai

PY - 2003/9/15

Y1 - 2003/9/15

N2 - PURPOSE: The objectives of this study were to investigate the effects of anti-vascular endothelial growth factor (VEGF) treatment on various vascular functions, gene expression, and growth of orthotopic human pancreatic cancer xenografts and thus to provide useful preclinical data for novel cancer treatments.EXPERIMENTAL DESIGN: Small pieces of a human pancreatic carcinoma, PANC-1, were implanted into the pancreas of male severe combined immunodeficient mice. The animals were treated with anti-human VEGF antibody A.4.6.1 (300 micro g, every 3 days i.p.) or a nonspecific IgG between 4 and 8 weeks after tumor implantation. Then, vascular density, diameter, permeability, and tumor growth were determined by intravital microscopy. Subsequently, tumors were harvested, and angiogenic gene expression profile was determined by a microarray kit including 96 genes involved in tumor angiogenesis.RESULTS: Anti-VEGF antibody significantly reduced angiogenesis and growth of orthotopic PANC-1 tumors. In the anti-VEGF treatment group, the vessel density was significantly smaller (67.8 +/- 10.6 cm/cm(2)) than that seen in the control group (146.7 +/- 10.0 cm/cm(2)). However, vessel diameter and permeability were not altered significantly by anti-VEGF antibody treatment. The pancreatic tumors in the treated group were significantly smaller than those in the control group. Microarray and subsequent Northern blot and semiquantitative reverse transcription-PCR analyses revealed both a decrease (fibroblast growth factor 1, transforming growth factor beta1, platelet-derived growth factor alpha, erbB2, and c-ets1,) and an increase (placenta growth factor, hypoxia-inducible factor alpha, and endoglin) in expression of angiogenesis-related genes in the PANC-1 tumors by anti-VEGF treatment.CONCLUSIONS: Anti-VEGF antibody treatment has differential effects on vessel functions as well as angiogenic gene expression and inhibitory effects on angiogenesis and growth of the orthotopic pancreatic tumor. Anti-VEGF strategy appears promising for pancreatic cancer treatment.

AB - PURPOSE: The objectives of this study were to investigate the effects of anti-vascular endothelial growth factor (VEGF) treatment on various vascular functions, gene expression, and growth of orthotopic human pancreatic cancer xenografts and thus to provide useful preclinical data for novel cancer treatments.EXPERIMENTAL DESIGN: Small pieces of a human pancreatic carcinoma, PANC-1, were implanted into the pancreas of male severe combined immunodeficient mice. The animals were treated with anti-human VEGF antibody A.4.6.1 (300 micro g, every 3 days i.p.) or a nonspecific IgG between 4 and 8 weeks after tumor implantation. Then, vascular density, diameter, permeability, and tumor growth were determined by intravital microscopy. Subsequently, tumors were harvested, and angiogenic gene expression profile was determined by a microarray kit including 96 genes involved in tumor angiogenesis.RESULTS: Anti-VEGF antibody significantly reduced angiogenesis and growth of orthotopic PANC-1 tumors. In the anti-VEGF treatment group, the vessel density was significantly smaller (67.8 +/- 10.6 cm/cm(2)) than that seen in the control group (146.7 +/- 10.0 cm/cm(2)). However, vessel diameter and permeability were not altered significantly by anti-VEGF antibody treatment. The pancreatic tumors in the treated group were significantly smaller than those in the control group. Microarray and subsequent Northern blot and semiquantitative reverse transcription-PCR analyses revealed both a decrease (fibroblast growth factor 1, transforming growth factor beta1, platelet-derived growth factor alpha, erbB2, and c-ets1,) and an increase (placenta growth factor, hypoxia-inducible factor alpha, and endoglin) in expression of angiogenesis-related genes in the PANC-1 tumors by anti-VEGF treatment.CONCLUSIONS: Anti-VEGF antibody treatment has differential effects on vessel functions as well as angiogenic gene expression and inhibitory effects on angiogenesis and growth of the orthotopic pancreatic tumor. Anti-VEGF strategy appears promising for pancreatic cancer treatment.

KW - Animals

KW - Antibodies

KW - Base Sequence

KW - Capillary Permeability

KW - Cell Division

KW - DNA Primers

KW - Gene Expression Regulation, Neoplastic

KW - Humans

KW - Male

KW - Mice

KW - Mice, SCID

KW - Neovascularization, Pathologic

KW - Neutralization Tests

KW - Oligonucleotide Array Sequence Analysis

KW - Pancreatic Neoplasms

KW - Reverse Transcriptase Polymerase Chain Reaction

KW - Transcription, Genetic

KW - Transplantation, Heterologous

KW - Vascular Endothelial Growth Factor A

M3 - SCORING: Journal article

C2 - 14519649

VL - 9

SP - 4221

EP - 4226

JO - CLIN CANCER RES

JF - CLIN CANCER RES

SN - 1078-0432

IS - 11

ER -