Magnetic Resonance Imaging Detects Suppression of Tumor Vascular Permeability After Administration of Antibody to Vascular Endothelial Growth Factor

Cd, Pham; Roberts, Timothy P.L.; N, van Bruggen; Melnyk, Ostap; Mann, Jeffry S.; Ferrara, Napoleone; Rl, Cohen; Rc, Brasch

doi:10.3109/07357909809039771

Cited by 195 publications

(122 citation statements)

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“…Tumor growth was strongly inhibited or stabilized in all AG-013736 treated animals, with an average decrease of tumor volume of Ϫ12% Ϯ 16% after seven days (N ϭ 8, P ϭ 0.06). Five tumors with an initial size of 400 -700 mm 3 began to shrink after seven days of AG-013736 treatment (P Ͻ 0.05), while the other three tumors with an initial size of 200 -270 mm 3 were stabilized compared to the fast growth of the tumor with a similar initial size in the control group (increased 103% during seven days). Figure 2 compares group standard histograms of K ps at baseline (solid line) and day 7 (dashed line) in control ( Fig.…”

Section: Resultsmentioning

confidence: 99%

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Heterogeneity in the angiogenic response of a BT474 human breast cancer to a novel vascular endothelial growth factor‐receptor tyrosine kinase inhibitor: Assessment by voxel analysis of dynamic contrast‐enhanced MRI

Wilmes

Henry

et al. 2005

Magnetic Resonance Imaging

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Purpose:To investigate the heterogeneity in the angiogenic response of a human breast cancer xenograft to a novel vascular endothelial growth factor (VEGF)-receptor tyrosine kinase inhibitor, AG-013736, using dynamic contrast-enhanced MR imaging (DCE-MRI). Materials and Methods:Changes in pharmacokinetic parameters in a seven-day interval were compared between AG-treated and control groups, using Gd-DTPA and albumin-(Gd-DTPA) 30 . A voxel-by-voxel analysis was performed to produce parametric spatial pharmacokinetic parametric maps and histograms. Histogram segmentation was used to quantify the heterogeneity in tumor response to therapy, and compared with conventional descriptive measures of distribution in terms of their capacity to separate control from AG-treated tumors. Results:The albumin-(Gd-DTPA) 30 endothelial transfer constant, K ps , showed changes with AG-013736 treatment and tumor growth. The changes were highly heterogeneous for individual segments of the histogram with different K ps values, and the overall patterns in which the frequency distribution changed differed significantly between the two groups. A change in the number of voxels with K ps rangingfrom 0.03 to 0.14 mL/min/(100 mL tissue) was the most sensitive variable for separating control from AGtreated tumors (P ϭ 0.0008). Parametric maps of the kinetic parameters also showed spatial heterogeneity in tumor response to treatment. The K ps maps depicted rapid development of central necrosis as a result of AG-013736 treatment. Maps of v p demonstrated a marked increase at peripheral regions of necrotic areas. Similar trends were noted in the Gd-DTPA rate constant K trans distribution. Conclusion:This study demonstrates the value of histogram analysis of maps of pharmacokinetic parameters for assessing heterogeneity in tumor response to antiangiogenic therapy. Changes in the number of voxels within certain segments of the K ps histogram were the most sensitive variable for separating control from AG-treated tumors.Key Words: magnetic resonance imaging; human breast cancer xenograft; vascular endothelial growth factor receptor tyrosine kinase inhibitor; contrast media; endothelial permeability J. Magn. Reson. Imaging 2005;22:511-519.

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Section: Resultsmentioning

confidence: 99%

“…For the imaging studies, the tumors were allowed to grow to an average volume of 400 -500 mm 3 prior to dosing with the VEGF-receptor tyrosine kinase inhibitor, AG-013736. The mice were selected from a larger cohort that had been implanted on the same day, and the tumors were size-matched.…”

Section: Tumor Model and Treatmentmentioning

confidence: 99%

Heterogeneity in the angiogenic response of a BT474 human breast cancer to a novel vascular endothelial growth factor‐receptor tyrosine kinase inhibitor: Assessment by voxel analysis of dynamic contrast‐enhanced MRI

Wilmes

Henry

et al. 2005

Magnetic Resonance Imaging

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“…There was no inhibitory effect exerted on the growth of cancer cells in vitro, and treated tumors showed reduced vascularity [33] and reduced interstitial pressure [32,35]. In addition to inhibition of the primary tumor, reduction in metastases was also observed in some studies [36][37][38].…”

Section: Bevacizumab In Nsclc Preclinical Studiesmentioning

confidence: 84%

“…Bevacizumab, or its parent murine antibody A.4.6.1, inhibits the growth of various human tumor cell types in murine xenograft models [31][32][33], including the CALU-6 NSCLC model [34]. There was no inhibitory effect exerted on the growth of cancer cells in vitro, and treated tumors showed reduced vascularity [33] and reduced interstitial pressure [32,35].…”

Section: Bevacizumab In Nsclc Preclinical Studiesmentioning

confidence: 99%

Non-Small Cell Lung Cancer and Antiangiogenic Therapy: What Can Be Expected of Bevacizumab?

Herbst

Sandler

2004

The Oncologist

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There is an urgent need for new therapies to treat nonsmall cell lung cancer (NSCLC), as progress with current chemotherapy regimens has been limited. The roles of vascular endothelial growth factor (VEGF) in promoting tumor angiogenesis, maintaining existing vasculature, and contributing to resistance to traditional therapies, together with its negative prognostic significance in NSCLC, make it an appropriate target for therapy. Bevacizumab (Avastin TM ; Genentech Inc., South San Fransisco, CA), a monoclonal antibody directed against VEGF, has shown promise in treating a number of different cancers. In a recent phase II trial in patients with advanced metastatic NSCLC, the addition of bevacizumab to standard carboplatin/paclitaxel chemotherapy produced a significantly longer time to progression (32.1 versus 18.4 weeks) and greater response rate (31% versus 19% [not significant]) than chemotherapy alone. In the subset of patients with nonsquamous histologies, response rates and survival were further enhanced, with a mean survival time of 17.9 months versus 12.3 months with chemotherapy alone.Bevacizumab was generally well tolerated and did not appear to increase the incidences or severities of the nausea/vomiting, neuropathy, and renal toxicity that are typically associated with carboplatin/paclitaxel chemotherapy. Adverse events in phase I and II studies included hypertension, thrombosis, proteinuria (with occasional nephrotic syndrome), and epistaxis. Serious tumor-related bleeding episodes (hemoptysis/hematemesis) appear to be the main safety concern in patients with NSCLC, with squamous cell histology as a possible risk factor.Further work is needed to identify the best way to use bevacizumab in NSCLC, including use in combination with other biologic agents and in the adjuvant setting. The Oncologist 2004;9(suppl 1):19-26 The Oncologist 2004;9(suppl 1):19-26 www.TheOncologist.comCorrespondence: Roy S. Herbst, M.D., M.D. Anderson Cancer Center, Department of Head and Neck Medical Oncology, 1515 Holcombe Boulevard, Houston, Texas 77030, USA. Telephone: 713-792-6363; Fax: 713-796-8655; e-mail: rherbst@mdanderson.org Received November 25, 2003; accepted for publication January 15, 2004. ©AlphaMed Press 1083-7159/2004 The Oncologist ® LEARNING OBJECTIVESAfter completing this course, the reader will be able to:1. Identify the role of angiogenesis in non-small cell lung cancer (NSCLC).2. Explain the role of bevacizumab in apparently producing greater response, time to progression, and overall survival rates in a randomized phase II trial comparing carboplatin, paclitaxel, and bevacizumab with carboplatin and paclitaxel without bevacizumab and the limitations of this interpretation.3. Define the main toxicity concerns with the use of bevacizumab in the treatment of NSCLC.Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com CME CMEThis material is protected by U.S. Copyright law. Unauthorized reproduction is prohibited. For reprints contact: Repr...

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“…However, those data might influence the controversially discussed issue of timing of breast cancer surgery during the menstrual cycle (Hagen and Hrushesky, 1998) and VEGF secretion of the breast could contribute to menstrual cycle-dependent changes in serum levels of VEGF (Benoy et al, 1998;Chung et al, 1998;Heer et al, 1998). Since MRI of the breast seems to be especially susceptible for VEGF-induced changes in microvascular functions like vessel permeability, as could be shown by anti-VEGF treatment in nude mice (Pham et al, 1998), it seems reasonable to expect that the hormonal exposure of the breast influences parenchymal contrast enhancement patterns. This may explain why these patterns are changing depending on the stage of the patients' menstrual cycle (Müller-Schimpfle et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

Vascular endothelial growth factor A (VEGF-A) mRNA expression levels decrease after menopause in normal breast tissue but not in breast cancer lesions

Greb¹,

Maier²,

Wallwiener³

et al. 1999

Br J Cancer

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SummaryWe hypothesized that the regulation of microvascular functions and angiogenesis in breast tissue, a well known target of ovarian steroid action, is dependent on the hormonal exposure of the breast. Relative expression levels of VEGF-A (vascular endothelial growth factor A), a putative key regulator of angiogenesis in breast cancer, were analysed in the tumour and the adjacent non-neoplastic breast tissue of 19 breast cancer patients by quantitative reverse transcriptase polymerase chain reaction. In non-neoplastic breast specimens the expression levels of all detected VEGF-A-isoforms (189, 165, 121) were significantly higher in premenopausal compared to post-menopausal women (P = 0.02) and were inversely correlated with the patient's age (P = 0.006). In contrast, in cancerous tissues menopausal status had no influence on VEGF-A-expression levels. Benign and malignant tissues exhibited a similar expression pattern of VEGF-A-isoforms relative to each other. Thus, the regulation of the vasculature in normal breast tissue, as opposed to breast cancer tissue, appears to be hormonally dependent. Endogenous and therapeutically used hormonal steroids might, therefore, cause clinically relevant changes of the angiogenic phenotype of the human breast.

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Magnetic Resonance Imaging Detects Suppression of Tumor Vascular Permeability After Administration of Antibody to Vascular Endothelial Growth Factor

Cited by 195 publications

References 9 publications

Heterogeneity in the angiogenic response of a BT474 human breast cancer to a novel vascular endothelial growth factor‐receptor tyrosine kinase inhibitor: Assessment by voxel analysis of dynamic contrast‐enhanced MRI

Heterogeneity in the angiogenic response of a BT474 human breast cancer to a novel vascular endothelial growth factor‐receptor tyrosine kinase inhibitor: Assessment by voxel analysis of dynamic contrast‐enhanced MRI

Non-Small Cell Lung Cancer and Antiangiogenic Therapy: What Can Be Expected of Bevacizumab?

Vascular endothelial growth factor A (VEGF-A) mRNA expression levels decrease after menopause in normal breast tissue but not in breast cancer lesions

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