| Object:1.To investigate the effect and safety of implanted radioactive 125I seeds of different dosage on normal tissue structure of bronchus,esophagus, pulmonary artery, pulmonary vein in dogs, to search the maximum tolerance of normal tissue .2.To study the 125I seeds inhibition to the A549 cell growth and to make the growth curve of the A549 cell line basing on MTT (or cell counting) method results, by using 125I seeds of different dosage in the cell experiment in vitro. In order to search the minimum effective dosage of 125I seeds for NSCLC.3.To discuss the clinic application and the treatment effect of implanted 125I seeds for NSCLC.Method:1.Nine healthy male dogs weighing 17～21kg were randomly divided into three groups: 30,60 days group and control group. A design radioactive seed was transplanted by the side of bronchus, esophagus, pulmonary artery, pulmonary vein according to different groups respectively, taking the organization of bronchus, esophagus, pulmonary artery, pulmonary vein after transplanting to carry on the dyeing of HE according to time, observing pathologic variety of the organization under light microscope. In the control group, the bronchus,esophagus, pulmonary artery, pulmonary vein in dogs are separated for about 1.0cm, but no radioactive seed was transplanted.2.making the growth curve of the A549 cell line basing on MTT (or cell counting) method results, which indicate the impact of the iodine-125 seeds of different dosage upon the A549 cell growth. At the same time, the value of IC50 were also recorded. the animal tumor model were divided into five groups (one group contains 6 nude mice), each group receiving the different dosage of iodine-125 seeds respectively (high-, middle-, low-, zero-, control). The width and length of tumor, in order to calculate the volume, were measured every four days till four weeks, when the tumor mass were dissected for the further examination such as immunhistochemical stain (VEGF, PCNA., p53), TUNEL (to find the degree of apoptosis induced by the different dosage of iodine-125), and electron microscope (to find the morphological change of the position different distance away from the irradiation seeds。3.From the 20 cases, the radioactive seeds were transplanted through the skin in 12 cases, the rest were transplanted on the tumor sites in operation. We analysis the results after visiting the patients.Results:1. The result shows that in the 30 days group the pulmonary artery and blab of lung are damaged lightly, but 60 days group is not damaged obviously. The tissues in experimental groups had different damages , but the tissue damage was reversibility. With the time past, the damage can be reconverted.2. After making the growth curve of the A549 cell line, we found that the IC50 of A549 is 0.4mCi with radioactive 125I seeds. In the in vivo study, the inhibitory rate by different dosage in the A549 nude mouse tumor model were73.38 %, 53.17%, 23.89% respectively. The expression of VEGF, PCNA in iodine-125 group were found significantly lower than the control. At the same time, the phenomenon of high degree apoptosis were found in iodine-125 group. As for the expression of P53, there was remarked difference between the treatment and the control group, and the same result was also observed between the high/middle dosage and the lower dosage group.3. The tumors in the group of through skin acupuncture had remarked decreased. After the operation ,the symptom turns better. Until now , there is no death case after the operation, and the longest living is 27 months. There is no tumor-reviving case in the group of implantating seeds on the place of tumor. One is dead of tumor transfer to bone 6 months after the operation.Conclusion:1.Radioactive 125I seed has little harm on normal tissue structure of of bronchus,esophagus, pulmonary artery, pulmonary vein in dogs. the tissues don't appear the complications such as perforation, bleeding, necrosis, etc. The tissue damage was little and reversibility. With the time past, the damage can be reconverted, i.e. the damage is not permanent.2. The experiment verified that 125I seed is effective in the treatment of NSCLC, the method can be used clinically for the NSCLC patients, especially for the patients who are not suitable for operation. The dosage does not exceed 0.8mci, i.e. 0.3-0.7mCi. We choose the dosage of 0.4-0.8mCi, it could kill the tumor, as well as not cause the permanent damage . Iodine-125 interstitial brachytherapy decrease the expression of VEGF and PCNA as well as induces the expression of P53.3. The treatment of implantating seeds through skin acupuncture is effective method on NSLC for the heart and lung dysfunction patients, which have not been found transfer to else body. The method is also used into the patients that is doubted that his tumor is not resecting all. The method can also be in use of prevention of tumor reviving. |
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