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Science 16 January 1998:
Vol. 279. no. 5349, pp. 377 - 380
DOI: 10.1126/science.279.5349.377
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Reports

Cancer Treatment by Targeted Drug Delivery to Tumor Vasculature in a Mouse Model

Wadih Arap, * Renata Pasqualini, * Erkki Ruoslahti dagger

In vivo selection of phage display libraries was used to isolate peptides that home specifically to tumor blood vessels. When coupled to the anticancer drug doxorubicin, two of these peptides--one containing an alpha v integrin-binding Arg-Gly-Asp motif and the other an Asn-Gly-Arg motif--enhanced the efficacy of the drug against human breast cancer xenografts in nude mice and also reduced its toxicity. These results indicate that it may be possible to develop targeted chemotherapy strategies that are based on selective expression of receptors in tumor vasculature.

Cancer Research Center, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
*   These authors contributed equally to this report.

dagger    To whom correspondence should be addressed. E-mail: ruoslahti{at}burnham-inst.org

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P. Holig, M. Bach, T. Volkel, T. Nahde, S. Hoffmann, R. Muller, and R. E. Kontermann (2004)
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   Abstract »    Full Text »    PDF »
A bispecific immunotoxin (DTAT13) targeting human IL-13 receptor (IL-13R) and urokinase-type plasminogen activator receptor (uPAR) in a mouse xenograft model.
D. A. Todhunter, W. A. Hall, E. Rustamzadeh, Y. Shu, S. O. Doumbia, and D. A. Vallera (2004)
Protein Eng. Des. Sel. 17, 157-164
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{alpha}v{beta}3 and {alpha}v{beta}5 Integrins Bind Both the Proximal RGD Site and Non-RGD Motifs within Noncollagenous (NC1) Domain of the {alpha}3 Chain of Type IV Collagen: IMPLICATION FOR THE MECHANISM OF ENDOTHELIAL CELL ADHESION.
V. Pedchenko, R. Zent, and B. G. Hudson (2004)
J. Biol. Chem. 279, 2772-2780
   Abstract »    Full Text »    PDF »
Coupling Tumor Necrosis Factor-{alpha} with {alpha}V Integrin Ligands Improves Its Antineoplastic Activity.
F. Curnis, A. Gasparri, A. Sacchi, R. Longhi, and A. Corti (2004)
Cancer Res. 64, 565-571
   Abstract »    Full Text »    PDF »
Measuring tumour vascular response to antivascular and antiangiogenic drugs.
G M Tozer (2003)
Br. J. Radiol. 76, S23-S35
   Abstract »    Full Text »    PDF »
Nucleolin expressed at the cell surface is a marker of endothelial cells in angiogenic blood vessels.
S. Christian, J. Pilch, M. E. Akerman, K. Porkka, P. Laakkonen, and E. Ruoslahti (2003)
J. Cell Biol. 163, 871-878
   Abstract »    Full Text »    PDF »
Vascular Damage and Anti-angiogenic Effects of Tumor Vessel-Targeted Liposomal Chemotherapy.
F. Pastorino, C. Brignole, D. Marimpietri, M. Cilli, C. Gambini, D. Ribatti, R. Longhi, T. M. Allen, A. Corti, and M. Ponzoni (2003)
Cancer Res. 63, 7400-7409
   Abstract »    Full Text »    PDF »
Fluorescence Imaging of Multiple Myeloma Cells in a Clinically Relevant SCID/NOD in Vivo Model: Biologic and Clinical Implications.
C. S. Mitsiades, N. S. Mitsiades, R. T. Bronson, D. Chauhan, N. Munshi, S. P. Treon, C. A. Maxwell, L. Pilarski, T. Hideshima, R. M. Hoffman, et al. (2003)
Cancer Res. 63, 6689-6696
   Abstract »    Full Text »    PDF »
Identification of a dengue virus type 2 (DEN-2) serotype-specific B-cell epitope and detection of DEN-2-immunized animal serum samples using an epitope-based peptide antigen.
H.-C. Wu, M.-Y. Jung, C.-Y. Chiu, T.-T. Chao, S.-C. Lai, J.-T. Jan, and M.-F. Shaio (2003)
J. Gen. Virol. 84, 2771-2779
   Abstract »    Full Text »    PDF »
Comparison of Three Different Targeted Tissue Factor Fusion Proteins for Inducing Tumor Vessel Thrombosis.
P. Hu, J. Yan, J. Sharifi, T. Bai, L. A. Khawli, and A. L. Epstein (2003)
Cancer Res. 63, 5046-5053
   Abstract »    Full Text »    PDF »
Use of Real-Time Polymerase Chain Reaction to Identify Cell- and Tissue-Type-Selective Peptides by Phage Display.
D. L. Jaye, F. S. Nolte, L. Mazzucchelli, C. Geigerman, A. Akyildiz, and C. A. Parkos (2003)
Am. J. Pathol. 162, 1419-1429
   Abstract »    Full Text »    PDF »
Doxorubicin-loaded Fab' Fragments of Anti-disialoganglioside Immunoliposomes Selectively Inhibit the Growth and Dissemination of Human Neuroblastoma in Nude Mice.
F. Pastorino, C. Brignole, D. Marimpietri, P. Sapra, E. H. Moase, T. M. Allen, and M. Ponzoni (2003)
Cancer Res. 63, 86-92
   Abstract »    Full Text »    PDF »
Domain Swapping in a COOH-terminal Fragment of Platelet Factor 4 Generates Potent Angiogenesis Inhibitors.
M. Hagedorn, L. Zilberberg, J. Wilting, X. Canron, G. Carrabba, C. Giussani, M. Pluderi, L. Bello, and A. Bikfalvi (2002)
Cancer Res. 62, 6884-6890
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An Ephrin Mimetic Peptide That Selectively Targets the EphA2 Receptor.
M. Koolpe, M. Dail, and E. B. Pasquale (2002)
J. Biol. Chem. 277, 46974-46979
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Structure-Activity Relationships of Linear and Cyclic Peptides Containing the NGR Tumor-homing Motif.
G. Colombo, F. Curnis, G. M. S. De Mori, A. Gasparri, C. Longoni, A. Sacchi, R. Longhi, and A. Corti (2002)
J. Biol. Chem. 277, 47891-47897
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Targeting Multiple Biological Pathways as a Strategy to Improve the Treatment of Cancer.
M. S. O'Reilly (2002)
Clin. Cancer Res. 8, 3309-3310
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Nanocrystal targeting in vivo.
M. E. Akerman, W. C. W. Chan, P. Laakkonen, S. N. Bhatia, and E. Ruoslahti (2002)
PNAS 99, 12617-12621
   Abstract »    Full Text »    PDF »
Teratogenicity induced by targeting a placental immunoglobulin transporter.
M. G. Kolonin, R. Pasqualini, and W. Arap (2002)
PNAS 99, 13055-13060
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Arginine-Glycine-Aspartic Acid (RGD)-Peptide Binds to Both Tumor and Tumor-Endothelial Cells in Vivo.
S. Zitzmann, V. Ehemann, and M. Schwab (2002)
Cancer Res. 62, 5139-5143
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Phase I Study of Recombinant Human Endostatin in Patients With Advanced Solid Tumors.
R. S. Herbst, K. R. Hess, H. T. Tran, J. E. Tseng, N. A. Mullani, C. Charnsangavej, T. Madden, D. W. Davis, D. J. McConkey, M. S. O'Reilly, et al. (2002)
J. Clin. Oncol. 20, 3792-3803
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Mechanisms and Future Directions for Angiogenesis-Based Cancer Therapies.
F. A. Scappaticci (2002)
J. Clin. Oncol. 20, 3906-3927
   Abstract »    Full Text »    PDF »


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