التفاصيل البيبلوغرافية
| العنوان: |
Low-Dose Sorafenib Promotes Cancer Stem Cell Expansion and Accelerated Tumor Progression in Soft Tissue Sarcomas |
| المؤلفون: |
Cruz, Sylvia M, Iranpur, Khurshid R, Judge, Sean J, Ames, Erik, Sturgill, Ian R, Farley, Lauren E, Darrow, Morgan A, Crowley, Jiwon Sarah, Monjazeb, Arta M, Murphy, William J, Canter, Robert J |
| المصدر: |
International Journal of Molecular Sciences, vol 25, iss 6 |
| بيانات النشر: |
eScholarship, University of California |
| سنة النشر: |
2024 |
| المجموعة: |
University of California: eScholarship |
| مصطلحات موضوعية: |
Biochemistry and Cell Biology, Biological Sciences, Medicinal and Biomolecular Chemistry, Chemical Sciences, Microbiology, Stem Cell Research - Nonembryonic - Human, Stem Cell Research, Stem Cell Research - Nonembryonic - Non-Human, Clinical Research, Cancer, cancer stem cells, sorafenib, ALDH, sarcoma, survival, Cell Line, Tumor, Humans, Aldehyde Dehydrogenase, Protein Kinase Inhibitors, Neoplastic Stem Cells, Tyrosine Kinase Inhibitors, Other Chemical Sciences, Genetics, Other Biological Sciences, Chemical Physics |
| الوقت: |
3351 |
| الوصف: |
The cancer stem cell (CSC) hypothesis postulates that heterogeneous human cancers harbor a population of stem-like cells which are resistant to cytotoxic therapies, thus providing a reservoir of relapse following conventional therapies like chemotherapy and radiation (RT). CSCs have been observed in multiple human cancers, and their presence has been correlated with worse clinical outcomes. Here, we sought to evaluate the impact of drug dosing of the multi-tyrosine kinase inhibitor, sorafenib, on CSC and non-CSCs in soft tissue sarcoma (STS) models, hypothesizing differential effects of sorafenib based on dose and target cell population. In vitro, human cancer cell lines and primary STS from surgical specimens were exposed to escalating doses of sorafenib to determine cell viability and expression of CSC marker aldehyde dehydrogenase (ALDH). In vivo, ALDHbright CSCs were isolated, exposed to sorafenib, and xenograft growth and survival analyses were performed. We observed that sarcoma CSCs appear to paradoxically respond to the tyrosine kinase inhibitor sorafenib at low doses with increased proliferation and stem-like function of CSCs, whereas anti-viability effects dominated at higher doses. Importantly, STS patients receiving neoadjuvant sorafenib and RT on a clinical trial (NCT00864032) showed increased CSCs post therapy, and higher ALDH scores post therapy were associated with worse metastasis-free survival. These data suggest that low-dose sorafenib may promote the CSC phenotype in STS with clinically significant effects, including increased tumor growth and higher rates of metastasis formation in sarcoma patients. |
| نوع الوثيقة: |
article in journal/newspaper |
| وصف الملف: |
application/pdf |
| اللغة: |
unknown |
| العلاقة: |
qt1w55t3g7; https://escholarship.org/uc/item/1w55t3g7Test |
| الإتاحة: |
https://escholarship.org/uc/item/1w55t3g7Test |
| حقوق: |
public |
| رقم الانضمام: |
edsbas.2F594E20 |
| قاعدة البيانات: |
BASE |
