NGF Blockade at Early Times during Bone Cancer Development Attenuates Bone Destruction and Increases Limb Use
| Autor: | Geraldine Longo, Lisa A. Majuta, Michelle N. Fealk, Stephane R. Chartier, Patrick W. Mantyh, Michelle L. Thompson, Gwen McCaffrey |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Cancer Research medicine.medical_specialty Pathology Pain Bone Neoplasms Osteoarthritis Bone Sarcoma Antibodies Article Metastasis Mice Random Allocation Cell Line Tumor Internal medicine Nerve Growth Factor medicine Animals Nerve Growth Factors Neoplasm Metastasis Mice Inbred C3H business.industry Bone cancer Extremities Sarcoma Bone fracture medicine.disease Blockade Disease Models Animal Nerve growth factor Endocrinology Oncology Head and Neck Neoplasms business |
| Zdroj: | Cancer Research. 74:7014-7023 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/0008-5472.can-14-1220 |
| Popis: | 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. Cancer Res; 74(23); 7014–23. ©2014 AACR. |
| Databáze: | OpenAIRE |
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