Study on radioresistence of the cells under a hypoxic condition

1) ZD1839（“易瑞沙”）和曲妥珠单抗（“赫赛汀”）双重抑制HER家族放射敏感性增强ZD1839和/或曲妥珠单抗抑制辐射诱导的EGFR和HER2/neu激活。放疗联合HER家族抑制剂也抑制了HER家族下游生存信号Akt和MEK1/2的激活。ZD1839增强了放射敏感性，DMF （SF3）为1.45，曲妥珠单抗的DMF （SF3）为1.11。ZD 1839和曲妥珠单抗同时阻断HER2家族可诱导DMF （SF3）为2.29的协同放射增敏效应。HER家族的双重抑制通过抑制生存信号转导通路的激活协同增强放射敏感性。我们的研究表明，HER家族联合放射治疗可能是分子治疗靶点的有力候选之一。以A549细胞为实验对象，研究了低氧条件下（5% O_2和1% O_2）对细胞生长和放射敏感性的影响。1% O_2缺氧对细胞生长有明显抑制作用，5% O_2缺氧对细胞生长无明显抑制作用。1% O_2缺氧条件下的电镀效率与缺氧条件下的电镀效率相同。低氧条件下菌落的大小比缺氧条件下小，但抗辐射能力没有增加。3)低氧诱导因子1α的表达预测IIIB期宫颈鳞状细胞癌单独放疗后无转移生存在38例患者中，HIF-1α、p53、bax和bcl-2高表达的患者分别为17例（45%）、22例（58%）、15例（39%）和15例（39%），HPV感染阳性28例（74%）。HIF-1α高表达与疾病复发有显著正相关（p < 0.05）。HIF-1α与无复发生存率有显著相关性（p = 0.04）。HIF-1α高表达与局部控制率无统计学相关性（p = 0.17），而HIF-1α水平预测远处转移有很强的统计学意义（p = 0.03）。相反，其他因素对临床结果没有影响。目前的研究结果表明HIF-1α是一个重要的预后因素，特别是在预测IIIB期宫颈鳞状细胞癌放射治疗后的未来转移方面。少

1) Enhancement of Radiosensitivity by Dual Inhibition of HER family with ZD1839 ('Iressa') and Trastuzumab ('Herceptin')Radiation-induced activation of EGFR and HER2/neu was inhibited with ZD 1839 and/or trastuzumab. Radiation in combination with HER family inhibitors also inhibited the activation of Akt and MEK1/2, the downstream survival signaling of HER family. ZD1839 enhanced radiosensitivity with a DMF (SF3) of 1.45 and trastuzumab with a DMF (SF3) of 1.11. Simultaneous blockade of HER2 family by ZD 1839 and trastuzumab induced synergistic radiosensitizing effect with a DMF (SF3) of 2.29. A dual inhibition of HER family enhanced radiosensitivity synergistically by inhibiting activation of survival signal transduction pathway. Our study suggests that HER family in combination with radiation therapy may be one of the potent candidates for molecular therapeutic targets.2) Modification of cell growth and radiosensitivity under a hypoxic conditionReduction of radiosensitivity under the … More hypoxia (5% O_2 and 1% O_2) was investigated by using A549 cell in vitro. The cell growth was significantly inhibited under the condition with 1% O_2 hypoxia but not under the condition with 5% O_2 hypoxia. Plating efficiency under the condition with 1% O_2 hypoxia was the same as that under an oxic condition. Increase in radioresistance was not observed under a hypoxic condition although the sizes of colonies were smaller under the condition with 1% O_2 hypoxia compared with those under an oxic condition.3) Expression of hypoxic-inducible factor 1α predicts metastasis-free survival after radiation therapy alone in stage IIIB cervical squamous cell carcinomaOf 38 patients, high expression of HIF-1α, p53, bax, and bcl-2 were seen in 17 (45%), 22 (58%), 15 (39%), and 15 (39%) patients, respectively, and 28 patients (74%) showed positive infection with HPV. There was a significant positive correlation between high HIF-1α expression and disease recurrence (p < 0.05). Furthermore, HIF-1α had a significant correlation with the recurrence-free survival rate (p = 0.04). No statistical correlation was noted between high HIF-1α expression and the local control rate (p = 0.17), whereas the HIF-1α status predicted distant metastasis with strong significance (p = 0.03). Conversely, other factors demonstrated no impact on the clinical outcome. The present results suggest that HIF-1α is an important prognostic factor, especially for predicting future metastasis after radiation therapy for patients with Stage IIIB squamous cell carcinoma of the cervix. Less