Molecular parameters of hyperthermia for radiosensitization.
Molecular parameters of hyperthermia for radiosensitization.
复制标题
热疗的分子参数用于放射敏化。
DOI：
10.1615/critreveukargeneexpr.v19.i3.50
复制
发表时间：
2009
影响因子：
1.6
通讯作者：
Bhaumik SR
中科院分区：
文献类型：
--
作者：
Pandita TK;Pandita S;Bhaumik SR
高温是电离辐射（IR）杀伤细胞的一种有效增敏剂，然而，热诱导细胞死亡的确切机制尚不清楚。放射增敏可归因于热是一种多效性损伤剂，通过改变蛋白质结构在不同程度上影响多种细胞组分，从而影响DNA损伤反应。单独的热疗诱导与细胞中IR信号传导相关的几个步骤。例如，热疗增强ATM激酶活性并增加细胞ATM自磷酸化。ATM或IR诱导的信号传导途径的其他组分通过热的这种预先活化干扰了染色体DNA双链断裂修复所需的正常IR诱导的信号传导，从而导致照射后细胞杀伤增加。热疗还诱导热休克蛋白70（HSP70）的合成和增强端粒酶活性。热休克蛋白70表达与辐射抗性有关。HSP70和端粒酶的失活增加了IR暴露后残留的DNA DSB，这与增加的细胞杀伤相关，支持了HSP70和端粒酶在IR诱导的DNA损伤修复中的作用。因此，热疗会影响肿瘤细胞对辐射敏感的几个分子参数，并可增强靶向放射治疗的潜力。
Hyperthermia is a potent sensitizer of cell killing by ionizing radiation (IR), however, the precise mechanism of heat-induced cell death is not yet clear. Radiosensitization can be attributed to the fact that heat is a pleiotropic damaging agent, affecting multiple cell components to varying degrees by altering protein structures, thus influencing the DNA damage response. Hyperthermia alone induces several steps associated with IR signaling in cells. For example, hyperthermia enhances ATM kinase activity and increases cellular ATM autophosphorylation. This prior activation of ATM or other components of the IR-induced signaling pathway by heat interferes with the normal IR-induced signaling required for chromosomal DNA double-strand break repair, thus resulting in increased cell killing post irradiation. Hyperthermia also induces heat shock protein 70 (HSP70) synthesis and enhances telomerase activity. HSP70 expression is associated with radioresistance. Inactivation of HSP70 and telomerase increases residual DNA DSBs post IR exposure, which correlates with increased cell killing, supporting the role of HSP70 and telomerase in IR-induced DNA damage repair. Thus, hyperthermia influences several molecular parameters involved in sensitizing tumor cells to radiation and can enhance the potential of targeted radiotherapy.
登录
查看更多内容
DOI：
10.1073/pnas.152330499
发表时间：
2002-12-10
影响因子：
11.1
作者：
Bonini, NM
通讯作者：
Bonini, NM
影响因子：
2.9
作者：
Barker, K;Khayat, M;Bengtén, E
通讯作者：
Bengtén, E
影响因子：
4.8
作者：
Dai, RJ;Frejtag, W;Mivechi, NF
通讯作者：
Mivechi, NF
影响因子：
2.6
作者：
DahmDaphi, J;Brammer, I;Dikomey, E
通讯作者：
Dikomey, E
影响因子：
10.5
作者：
ABRAVAYA, K;PHILLIPS, B;MORIMOTO, RI
通讯作者：
MORIMOTO, RI