The Role of Oxidative Stress and Mitochondrial TERT in the Progression and Therapeutic Resistance of Papillary Thyroid Cancer.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- TERT mitochondrial localization (TERT/VDAC) in papillary thyroid tumors.
研究概览
简要总结
Oxidative stress (OS) could be involved in the progression of papillary thyroid cancer (PTC). Indeed, thyroid differentiation genes are silenced by a mechanism controlled by NOX4-derived OS. On the other hand, TERT contributes to mitochondrial OS protection, which could increase the resistance of cancer cells to therapeutic agents. The investigators aim to address the role of OS and mitochondrial TERT in the progression and therapeutic resistance of PTC. OS and TERT subcellular localization will be investigated in 150 PTCs and correlated to the genetic and expression profile of the tumors and to the clinical and prognostic features of the patients. Mechanisms implicated in TERT mitochondrial migration and the contribution of mitochondrial TERT to tumor progression will be investigated in cancer cell lines and primary cell cultures. This study will allow to identify OS as a marker of therapeutic resistance in PTC and will open new opportunities for the development of novel treatments targeting ROS generation/TERT nuclear export.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with papillary thyroid cancer
- •Patients whose tumor and contralateral healthy tissues can be collected for the analyses
排除标准
- •patients who did not provide consent
- •patients lost at follow-up
- •tissues not adequate for the analyses
结局指标
主要结局
TERT mitochondrial localization (TERT/VDAC) in papillary thyroid tumors.
时间窗: months 13-30
TERT mitochondrial localization will be investigated by Western blot of mitochondrial fractions and normalized to VDAC protein expression.
Proliferation in cells lines treated with Src kinase inhibitors.
时间窗: months 25-36
Proliferation will be measured by a colorimetric assay.
Apoptosis in cells lines treated with Src kinase inhibitors.
时间窗: months 25-36
Apoptosis will be measured by a luminometric assay.
Mitochondrial oxidative stress generation in cells lines treated with Src kinase inhibitors.
时间窗: months 25-36
Mitochondrial oxidative stress will be measured by immunofluorescence.
H202 generation (nmol/mg tissue) in papillary thyroid cancer and in corresponding normal tissues.
时间窗: months 1-24
Effect of exogenous oxidative stress (H2O2) and therapeutic agents (BRAF, MEK and Src kinase inhibitors) on TERT nuclear to mitochondrial translocation in thyroid cancer cell lines.
时间窗: month 19-30
TERT mitochondrial translocation will be measured by immunofluorescence.
Migration in cells lines treated with Src kinase inhibitors.
时间窗: months 25-36
Migration will be measured by wound healing assays.
次要结局
- Expression profile of tumor tissues.(months 1-24)
- Genetic characterization of tumor tissues.(months 1-24)