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Browsing by Author "Bracho, Olena"
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Item Inhibition of tropomyosine receptor kinase B on the migration of human Schwann cell and dispersion of oral tongue squamous cell carcinoma in vitro(Wiley, 2019-12) Ein, Liliana; Bracho, Olena; Mei, Christine; Patel, Jaimin; Boyle, Thomas; Monje, Paula; Fernandez‐Valle, Cristina; Bas, Esperanza; Thomas, Giovana; Weed, Donald; Sargi, Zoukaa; Dinh, Christine; Neurological Surgery, School of MedicineBackground Schwann cells (SC) may play an important role in perineural invasion (PNI) by promoting cancer cell dispersion. Brain‐derived neurotrophic factor (BDNF) may contribute to these cellular events by activating tropomyosine receptor kinase B (TrkB). This study examines the effect of TrkB inhibition on SC migration and oral cancer cell dispersion in vitro. Methods Human tongue squamous cell carcinoma (SCC‐9) and human SCs were cocultured in three different conditioned mediums: control, BDNF, and TrkB inhibitor. Cell migration, cancer cell dispersion, and SC dedifferentiation were measured on time‐lapse and immunofluorescence images. Results Cancer cell migration exceeded SC migration in all conditions. TrkB inhibition promoted SC dedifferentiation and significantly increased SC migration, when compared to BDNF conditions. TrkB inhibition also reduced cancer cell dispersion, when compared to control and BDNF‐treated cultures. Conclusion SCs may have importance in the pathophysiology of PNI. TrkB inhibition may be a potential avenue for therapeutic intervention.Item Merlin-Deficient Schwann Cells Are More Susceptible to Radiation Injury than Normal Schwann Cells In Vitro(Thieme, 2021-01-19) Cohen, Erin; Pena, Stefanie; Mei, Christine; Bracho, Olena; Marples, Brian; Elsayyad, Nagy; Goncalves, Stefania; Ivan, Michael; Monje, Paula V.; Liu, Xue-Zhong; Fernandez-Valle, Cristina; Telischi, Fred; Dinh, Christine T.; Neurological Surgery, School of MedicineObjectives: Vestibular schwannomas (VS) are intracranial tumors, which are caused by NF2 gene mutations that lead to loss of merlin protein. A treatment for VS is stereotactic radiosurgery, a form of radiation. To better understand the radiobiology of VS and radiation toxicity to adjacent structures, our main objectives were (1) investigate effects of single fraction (SF) radiation on viability, cytotoxicity, and apoptosis in normal Schwann cells (SCs) and merlin-deficient Schwann cells (MD-SCs) in vitro, and (2) analyze expression of double strand DNA breaks (γ-H2AX) and DNA repair protein Rad51 following irradiation. Study Design: This is a basic science study. Setting: This study is conducted in a research laboratory. Participants: Patients did not participate in this study. Main Outcome Measures: In irradiated normal SCs and MD-SCs (0–18 Gy), we measured (1) viability, cytotoxicity, and apoptosis using cell-based assays, and (2) percentage of cells with γ-H2AX and Rad51 on immunofluorescence. Results: A high percentage of irradiated MD-SCs expressed γ-H2AX, which may explain the dose-dependent losses in viability in rodent and human cell lines. In comparison, the viabilities of normal SCs were only compromised at higher doses of radiation (>12 Gy, human SCs), which may be related to less Rad51 repair. There were no further reductions in viability in human MD-SCs beyond 9 Gy, suggesting that <9 Gy may be insufficient to initiate maximal tumor control. Conclusion: The MD-SCs are more susceptible to radiation than normal SCs, in part through differential expression of γ-H2AX and Rad51. Understanding the radiobiology of MD-SCs and normal SCs is important for optimizing radiation protocols to maximize tumor control while limiting radiation toxicity in VS patients.