Thyroidectomy with neoadjuvant PLX4720 extends survival and decreases tumor burden in an orthotopic mouse model of anaplastic thyroid cancer
| Autor: | Sareh Parangi, Carmelo Nucera, Richard A. Hodin, Matthew A. Nehs, Sushruta S. Nagarkatti |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Proto-Oncogene Proteins B-raf
medicine.medical_specialty Pathology Indoles medicine.medical_treatment Urology Thyroid Carcinoma Anaplastic Polymorphism Single Nucleotide Article Cachexia Thyroid carcinoma Mice Cost of Illness Medicine Animals Thyroid Neoplasms Anaplastic thyroid cancer Thyroid cancer Neoadjuvant therapy Neoplasm Staging Sulfonamides business.industry Thyroid Body Weight Thyroidectomy Cancer medicine.disease Combined Modality Therapy Neoadjuvant Therapy Disease Models Animal medicine.anatomical_structure Surgery business Cell Division |
| Popis: | Background B-RafV600E is a frequent mutation in anaplastic thyroid cancers and is a novel therapeutic target. We hypothesized that PLX4720 (an inhibitor of B-RafV600E) and thyroidectomy would extend survival and would decrease tumor burden in a mouse model. Methods Orthotopic anaplastic thyroid tumors were induced in severe combined immunodeficient mice. Mice were treated with PLX4720 or vehicle after 7 days of tumor growth, and thyroidectomy or sham surgery was performed at day 14. The neck space was re-explored, and tumor volume was measured at day 35. Mice were sacrificed when they lost >25% of their initial weight. Results All 5 mice that received the vehicle developed cachexia, had invasive tumors (average 61 mm3)and were sacrificed by day 35. All 6 mice receiving PLX4720 + sham had small tumors (average 1.3 mm3) and maintained their weight. Three out of 6 mice receiving PLX4720+thyroidectomy had no evidence of tumor at 35 days; the other 3 mice had small tumors (average 1.4 mm3) and showed no signs of metastatic disease. All mice treated with PLX4720 were alive and well-appearing at 50 days. Conclusion Thyroidectomy with neoadjuvant PLX4720 could be an effective therapeutic strategy for early anaplastic thyroid cancers that harbor the B-RafV600E mutation and are refractory to conventional therapeutic modalities. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|