ABSTRACT
Objective To observe the influence of trastuzumab on DNA break repair and Her-2 nuclear import after radiation in breast cancer cell line SKBR3,and discuss the radiosensitivity mechanism of trastuzumab.Methods Clone formation assay was used to analyze the difference of survival fractions between radiation group and radiation plus trastuzumab group.Confocal microscopy was applied to observe the influence of trastuzumab in the nuclear import process of Her-2 and the expression of γH2AX after radiation,which is considered as the marker of DNA double strand break.Western blotting was used to detect the expression of Her-2 and DNA-PKcs in nuclei after radiation.Results The result of clone formation assayshowed that the SF2 in radiation group was 0.547±0.046 and 0.321±0.022 in the radiation plus trastuzumab group were significantly decreased,the results of confocal microscopy showed that trastuzumab postponed the nuclear import process of Her-2 (52.80±19.74 in radiation group,21.41±10.55 in the radiation group),and increased expression of γH2AX after radiation (85.40±25.63 in radiation group,18.53±44.32 in the radiation group),and western blotting revealed trastuzumab reduced the expression of Her-2,DNA-PKcs in nuclei.Conclusion Trastuzumab can inhibit the radiation induced nuclear import of Her-2,and decrease Her-2,DNA-PKcs in nuclei to increase the DSB on early stage after radiation.
ABSTRACT
From 1965 to 1986, 36 patients with Wilms' tumor were terated by nephrectomy,postoperative irradiation and chemotherapy. The radiation doses of 1540～3920cGy were given according to an age-medulated dose scheme. All except 4 Stage I received chemotherapy. The most commonly used chemotherapeutic agent was Act-D, VCR. The overall 5-year survival rate was 61.1%(22/36) and 10-year survival rate was 56%(14/25). The 5- and 10-year survival rates were 87.5% and 80% for Stage I, 63.2% and 61.5% for stage II,33.3% and 28.6% for stage III patents. The favorable factors which led to better results were: early stages(stages I,II) and aged under 5 years . The 5-year survival rates of Stages I,II and Stage III were 70.4%(19/27) and 33.3%(3/9), respectively(P