Abstract | PURPOSE: EXPERIMENTAL DESIGN: In initial studies, tumor-bearing nude mice were treated with a mixture of NT antibodies [100 microg each of anti- nerve growth factor ( NGF), anti- brain-derived neurotrophic factor, anti-NT-3, and anti-NT-4/5] or normal rabbit IgG (400 microg) intratumorally and peritumorally three times/week over a 15-day dosing period. In subsequent studies, tumor-bearing nude mice were treated with individual NT antibodies (100 microg), affinity-purified anti- NGF (0.1, 1.0, or 10.0 microg), or normal rabbit IgG (100 microg) using the same dosing schedule. RESULTS: Treatment with the antibody mixture inhibited significantly the growth of TSU-Pr1 and AsPC-1 xenografts as compared with IgG-treated controls (maximal inhibition of 53 and 53%, respectively), whereas this treatment caused significant regression in PC-3 xenografts. Treatment of TSU-Pr1 xenografts with either anti- NGF or anti-NT-3 resulted in maximal tumor growth inhibition of 67 and 64%, respectively, whereas anti- brain-derived neurotrophic factor and anti-NT-4/5 did not inhibit tumor growth in this tumor model. Administration of various concentrations (0.1, 1.0, or 10.0 microg) of affinity-purified anti- NGF resulted in maximal TSU-Pr1 tumor growth inhibition of 49, 62, and 66%, respectively. CONCLUSIONS: These data add further support for the therapeutic potential of disrupting trk-signaling events in select types of nonneuronal human cancers, specifically prostatic and pancreatic carcinomas.
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Authors | Sheila J Miknyoczki, Weihua Wan, Hong Chang, Pawel Dobrzanski, Bruce A Ruggeri, Craig A Dionne, Karen Buchkovich |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 8
Issue 6
Pg. 1924-31
(Jun 2002)
ISSN: 1078-0432 [Print] United States |
PMID | 12060637
(Publication Type: Journal Article)
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Chemical References |
- Immunoglobulin G
- Nerve Growth Factors
- Receptor, trkA
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Topics |
- Animals
- Carcinoma, Pancreatic Ductal
(metabolism, pathology, prevention & control)
- Cell Division
- Disease Progression
- Female
- Humans
- Immunoglobulin G
(therapeutic use)
- Male
- Mice
- Mice, Nude
- Nerve Growth Factors
(physiology)
- Pancreatic Neoplasms
(metabolism, pathology, prevention & control)
- Prostatic Neoplasms
(metabolism, pathology, prevention & control)
- Rabbits
- Receptor, trkA
(physiology)
- Reverse Transcriptase Polymerase Chain Reaction
- Signal Transduction
- Transplantation, Heterologous
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