| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Immunology |
First Department of Surgery, Tottori University School of Medicine, Yonago 683, Japan [T. N., K. S.]; Departments of Immunology [B. L. H., E. A. R.] and Pharmacology and Therapeutics [Y. M. R.] Roswell Park Cancer Institute, Buffalo, New York 14263; and Immunex Corporation, Seattle, Washington 98101 [M. B. W.]
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been reported to induce apoptosis in a variety of malignant cell lines, but it shows little or no toxicity in most normal cells. We examined the response of three human colon tumors to TRAIL alone and in combination with chemotherapy, using SCID mice engrafted with intact patient surgical specimens. These tumors, taken from fresh surgical specimens, contained the heterogeneous tumor cell population characteristic of patient tumors and showed differential sensitivity to TRAIL alone. We also investigated the effect of TRAIL in combination with chemotherapy, using one tumor that showed moderate sensitivity to TRAIL alone. Combining TRAIL with either 5-fluorouracil (5-FU) or CPT-11 (irinotecan hydrochloride) produced a greatly enhanced antitumor effect over that of either agent alone, with 50% of the animals achieving complete tumor regression with a combination of TRAIL and CPT-11. By histological analysis, tumors treated with TRAIL plus either 5-FU or CPT-11 were seen to consist mainly of connective tissue and fibrotic areas with only a few scattered tumor cells encapsulated in the connective tissue. Several markers were assessed to investigate the basis for the observed therapeutic effect, and significant induction of apoptosis was observed in tumors treated with curative combinations. Cytoplasmic and cell surface expression of the TRAIL receptors DR4 and DR5 was observed in this patient’s tumor by immunohistochemistry. Tumors treated with CPT-11 showed increased membrane expression of DR5, suggesting that CPT-11 may increase sensitivity to TRAIL by up-regulation of DR5. These results obtained in a relevant preclinical model support the idea that the use of TRAIL in combination with either 5-FU or CPT-11 may be an effective strategy in controlling human colon cancer.
This article has been cited by other articles:
|
|
 |
|
  M. R. Loebinger, A. Eddaoudi, D. Davies, and S. M. Janes Mesenchymal Stem Cell Delivery of TRAIL Can Eliminate Metastatic Cancer Cancer Res., May 15, 2009; 69(10): 4134 - 4142. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Ashkenazi, P. Holland, and S. G. Eckhardt Ligand-Based Targeting of Apoptosis in Cancer: The Potential of Recombinant Human Apoptosis Ligand 2/Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (rhApo2L/TRAIL) J. Clin. Oncol., July 20, 2008; 26(21): 3621 - 3630. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Shanker, A. D. Brooks, C. A. Tristan, J. W. Wine, P. J. Elliott, H. Yagita, K. Takeda, M. J. Smyth, W. J. Murphy, and T. J. Sayers Treating Metastatic Solid Tumors With Bortezomib and a Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Receptor Agonist Antibody J Natl Cancer Inst, May 7, 2008; 100(9): 649 - 662. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Contassot, K. Kerl, S. Roques, R. Shane, O. Gaide, M. Dupuis, A. H. Rook, and L. E. French Resistance to FasL and tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis in Sezary syndrome T-cells associated with impaired death receptor and FLICE-inhibitory protein expression Blood, May 1, 2008; 111(9): 4780 - 4787. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. C. DeRosier, D. J. Buchsbaum, P. G. Oliver, Z.-Q. Huang, J. C. Sellers, W. E. Grizzle, W. Wang, T. Zhou, K. R. Zinn, J. W. Long, et al. Combination Treatment with TRA-8 Anti Death Receptor 5 Antibody and CPT-11 Induces Tumor Regression in an Orthotopic Model of Pancreatic Cancer Clin. Cancer Res., September 15, 2007; 13(18): 5535s - 5543s. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Maddipatla, F. J. Hernandez-Ilizaliturri, J. Knight, and M. S. Czuczman Augmented Antitumor Activity against B-Cell Lymphoma by a Combination of Monoclonal Antibodies Targeting TRAIL-R1 and CD20 Clin. Cancer Res., August 1, 2007; 13(15): 4556 - 4564. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. C. Lee, D. A. Hamstra, M. S. Bhojani, A. P. Khan, B. D. Ross, and A. Rehemtulla Noninvasive Molecular Imaging Sheds Light on the Synergy between 5-Fluorouracil and TRAIL/Apo2L for Cancer Therapy Clin. Cancer Res., March 15, 2007; 13(6): 1839 - 1846. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Kim, T. R. Chaudhuri, D. J. Buchsbaum, D. Wang, and K. R. Zinn High-resolution single-photon emission computed tomography and X-ray computed tomography imaging of Tc-99m-labeled anti-DR5 antibody in breast tumor xenografts Mol. Cancer Ther., March 1, 2007; 6(3): 866 - 875. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. van Geelen, J. L. Westra, E. G. de Vries, W. Boersma-van Ek, N. Zwart, H. Hollema, H. M. Boezen, N. H. Mulder, J. T. Plukker, S. de Jong, et al. Prognostic Significance of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand and Its Receptors in Adjuvantly Treated Stage III Colon Cancer Patients J. Clin. Oncol., November 1, 2006; 24(31): 4998 - 5004. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Matsubara, Y. Mizutani, F. Hongo, H. Nakanishi, Y. Kimura, S. Ushijima, A. Kawauchi, T. Tamura, T. Sakata, and T. Miki Gene therapy with TRAIL against renal cell carcinoma. Mol. Cancer Ther., September 1, 2006; 5(9): 2165 - 2171. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Jalving, S. de Jong, J. J. Koornstra, W. Boersma-van Ek, N. Zwart, J. Wesseling, E. G.E. de Vries, and J. H. Kleibeuker TRAIL Induces Apoptosis in Human Colorectal Adenoma Cell Lines and Human Colorectal Adenomas. Clin. Cancer Res., July 15, 2006; 12(14): 4350 - 4356. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. M. Thai, A. Labrinidis, S. Hay, V. Liapis, S. Bouralexis, K. Welldon, B. J. Coventry, D. M. Findlay, and A. Evdokiou Apo2l/Tumor necrosis factor-related apoptosis-inducing ligand prevents breast cancer-induced bone destruction in a mouse model. Cancer Res., May 15, 2006; 66(10): 5363 - 5370. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Hasegawa, Y. Yamada, K. Komiyama, M. Hayashi, M. Ishibashi, T. Yoshida, T. Sakai, T. Koyano, T.-S. Kam, K. Murata, et al. Dihydroflavonol BB-1, an extract of natural plant Blumea balsamifera, abrogates TRAIL resistance in leukemia cells Blood, January 15, 2006; 107(2): 679 - 688. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J. Cohen, R. B. Cohen, and N. J. Meropol Targeting Signal Transduction Pathways in Colorectal Cancer--More Than Skin Deep J. Clin. Oncol., August 10, 2005; 23(23): 5374 - 5385. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Minderman, J. M. Conroy, K. L. O'Loughlin, D. McQuaid, P. Quinn, S. Li, L. Pendyala, N. J. Nowak, and M. R. Baer In vitro and in vivo irinotecan-induced changes in expression profiles of cell cycle and apoptosis-associated genes in acute myeloid leukemia cells Mol. Cancer Ther., June 1, 2005; 4(6): 885 - 900. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. A. Sinicrope, R. C. Penington, and X. M. Tang Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand-Induced Apoptosis Is Inhibited by Bcl-2 but Restored by the Small Molecule Bcl-2 Inhibitor, HA 14-1, in Human Colon Cancer Cells Clin. Cancer Res., December 15, 2004; 10(24): 8284 - 8292. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. A. Taylor, M. Senchyna, J. Flanagan, E. M. Joyce, D. O. Cliche, A. N. Boone, S. Culp-Stewart, and J. E. Thompson Role of eIF5A in TNF-{alpha}-Mediated Apoptosis of Lamina Cribrosa Cells Invest. Ophthalmol. Vis. Sci., October 1, 2004; 45(10): 3568 - 3576. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Jin, R. Yang, S. Fong, K. Totpal, D. Lawrence, Z. Zheng, J. Ross, H. Koeppen, R. Schwall, and A. Ashkenazi Apo2 Ligand/Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Cooperates with Chemotherapy to Inhibit Orthotopic Lung Tumor Growth and Improve Survival Cancer Res., July 15, 2004; 64(14): 4900 - 4905. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. C. Spierings, E. G. de Vries, E. Vellenga, F. A. van den Heuvel, J. J. Koornstra, J. Wesseling, H. Hollema, and S. de Jong Tissue Distribution of the Death Ligand TRAIL and Its Receptors J. Histochem. Cytochem., June 1, 2004; 52(6): 821 - 831. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Dai, P. Dent, and S. Grant Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) Promotes Mitochondrial Dysfunction and Apoptosis Induced by 7-Hydroxystaurosporine and Mitogen-Activated Protein Kinase Kinase Inhibitors in Human Leukemia Cells That Ectopically Express Bcl-2 and Bcl-xL Mol. Pharmacol., December 1, 2003; 64(6): 1402 - 1409. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Honma, Y. Ishii, Y. Yamamoto-Yamaguchi, T. Sassa, and K.-i. Asahi Cotylenin A, a Differentiation-inducing Agent, and IFN-{alpha} Cooperatively Induce Apoptosis and Have an Antitumor Effect on Human Non-Small Cell Lung Carcinoma Cells in Nude Mice Cancer Res., July 1, 2003; 63(13): 3659 - 3666. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
