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NGF blockade at early times during bone cancer development attenuates bone destruction and increases limb use.
- Source :
-
Cancer research [Cancer Res] 2014 Dec 01; Vol. 74 (23), pp. 7014-23. Date of Electronic Publication: 2014 Oct 06. - Publication Year :
- 2014
-
Abstract
- Studies in animals and humans show that blockade of nerve growth factor (NGF) attenuates both malignant and nonmalignant skeletal pain. While reduction of pain is important, a largely unanswered question is what other benefits NGF blockade might confer in patients with bone cancer. Using a mouse graft model of bone sarcoma, we demonstrate that early treatment with an NGF antibody reduced tumor-induced bone destruction, delayed time to bone fracture, and increased the use of the tumor-bearing limb. Consistent with animal studies in osteoarthritis and head and neck cancer, early blockade of NGF reduced weight loss in mice with bone sarcoma. In terms of the extent and time course of pain relief, NGF blockade also reduced pain 40% to 70%, depending on the metric assessed. Importantly, this analgesic effect was maintained even in animals with late-stage disease. Our results suggest that NGF blockade immediately upon detection of tumor metastasis to bone may help preserve the integrity and use, delay the time to tumor-induced bone fracture, and maintain body weight.<br /> (©2014 American Association for Cancer Research.)
- Subjects :
- Animals
Bone Neoplasms metabolism
Bone Neoplasms pathology
Cell Line, Tumor
Disease Models, Animal
Extremities pathology
Head and Neck Neoplasms drug therapy
Head and Neck Neoplasms metabolism
Head and Neck Neoplasms pathology
Male
Mice
Mice, Inbred C3H
Neoplasm Metastasis
Nerve Growth Factor metabolism
Nerve Growth Factors metabolism
Osteoarthritis drug therapy
Osteoarthritis metabolism
Osteoarthritis pathology
Pain drug therapy
Pain metabolism
Random Allocation
Sarcoma drug therapy
Sarcoma metabolism
Sarcoma pathology
Antibodies pharmacology
Bone Neoplasms drug therapy
Nerve Growth Factor antagonists & inhibitors
Nerve Growth Factors antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1538-7445
- Volume :
- 74
- Issue :
- 23
- Database :
- MEDLINE
- Journal :
- Cancer research
- Publication Type :
- Academic Journal
- Accession number :
- 25287160
- Full Text :
- https://doi.org/10.1158/0008-5472.CAN-14-1220