Study on radioresistence of the cells under a hypoxic condition

1)通过用ZD 1839（"易瑞沙"）和曲妥珠单抗（"赫赛汀"）双重抑制HER家族来增强放射敏感性用ZD 1839和/或曲妥珠单抗抑制辐射诱导的EGFR和HER2/neu活化。辐射与HER家族抑制剂组合也抑制HER家族下游存活信号传导Akt和MEK 1/2的活化。ZD 1839增强放射敏感性，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家族可诱导协同放射增敏效应，DMF（SF3）为2.29。HER家族的双重抑制通过抑制生存信号转导通路的激活而协同增强放射敏感性。我们的研究表明HER家族与放射治疗的结合可能是分子治疗靶点的潜在候选者之一。2）低氧条件下细胞生长和放射敏感性的改变低氧条件下细胞放射敏感性的降低 ...更多信息 采用体外培养A549细胞，观察了5%O_2和1%O_2低氧对细胞生长影响。1%O_2低氧对细胞生长有明显抑制作用，而5%O_2低氧对细胞生长无明显影响。在1%O_2低氧条件下的电镀效率与好氧条件下相同。低氧条件下，细胞集落的大小明显小于低氧条件下的集落，但低氧条件下细胞的放射抵抗性并没有增加。3）低氧诱导因子1 α的表达预测IIIB期宫颈鳞癌单纯放疗后的无转移生存率在38例患者中，HIF-1 α，p53，bax，bcl-2阳性表达分别为17例（45%）、22例（58%）、15例（39%）、15例（39%），HPV阳性28例（74%）。HIF-1 α高表达与肿瘤复发呈正相关（p <0.05）。此外，HIF-1 α与无复发生存率显著相关（p = 0.04）。HIF-1 α高表达与局部控制率之间无统计学相关性（p = 0.17），而HIF-1 α状态预测远处转移具有显著性意义（p = 0.03）。相反，其他因素对临床结果没有影响。目前的结果表明，HIF-1 α是一个重要的预后因素，特别是预测放射治疗后的IIIB期宫颈鳞状细胞癌患者的未来转移。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