The Lethal Effect Of Interstitial Brachytherapy With ¹⁰³Pd Seeds In Treatment Of The Human Gastric Tumor Xenografts In Nude Mice

Interstitial brachytherapy in treatment of human cancer is a good method which can greatly injury tumor by implanting radioactive microsources in the cancer tissue or nearby infiltratived tissue, including tissues suffused by lymph way which can irradiateγrays with low capacity continuously whereas normal tissue is not or slightly injuried. In early period , radioactive microsources release middle or high energy ray, it is not safe for neither operators nor patients. Also it is too trouble to operate and to do the quality control by the confine of the implantation specification. But after 80s last centery, because of the successful manufature of low energy radionuclide ,the appearance of 3D-treatment planning System , also with the development of imageology leading to cultivate such as B-ultrasonography and CT ,radioactive particle in the interstitial implant brachytherapy for malignant tumor shows excellent prospect. ¹⁰³Pd has its distinct superiority as a new radionuclide, it has the opportunity to be developed and utilized in the treatment of malignant tumor. There will be an extensive using perspective for ¹⁰³Pd to cure tumors of faster generation speed. It also has the chance to use in gastric cancer because its feature, such as the shorter half-life, the higher initial dose rate; low energy, the little damage to surrounding tissue and easy to protection. The gastric tumor is one of the most common digest tract tumor which may easily partly recur and transfer. Notwithstanding radical surgery plus adjuvant chemotherapy can achieve 30-50% survival rate, but 70% recurrence rate. So, there is short of effective therapeutic tool for recurrence tumor. Radiotherapy is still not be accept as conventional therapy yet because of the confine of normal stomach and intestine's low tolerance dose. Now, we will initial approach its lethal effect and draw out feasibility for clinical application by leading the ¹⁰³Pd in treatment of gastric cancer. At the same time, we will approach the mechanisms of radioactive particle in the interstitial implant brachytherapy for malignant tumor through observing the variation of surviving,p53,PCNA.Part I The Lethal Effect of Interstitial Brachytherapy with ¹⁰³Pd Seeds in Treatment of the Human Gastric Tumor Xenografts in Nude MiceObjective:To study the lethal effect and radiation injury of interstitial implantation with 103pd seeds in nude mice with the human gastric tumor through observing the pathology changes.Methods:Established the human gastric low score gland cancer BGC-823 cell nude mouse hypodermic transplant lump model,40 nude mice were randomly divided into the experimental group and the comparison group, the experimental group was implanted by the ¹⁰³Pd seed, according to the computer three dimensional treatment plan system compute distribution, the peripheral dosage was 120Gy. While the comparison group was implanted by the heat sink. Regularly observed the nude mice'tumor, the tumorous volume (mm3) were calculated according to formula v= a×b2/2. Transplantation tumor growth curve was drawing according to the formula calculate. The tumorous inhibition ratio (IR) = (Control group–Treated group) the average tumor volume/ the mean control group's tumor volume. Compared the tumor control rate to see whether the difference was significant when 17th day and 34th day. Pathological changes of tumor tissue were detected under light microscope after 17days and 34days. Tumor regression was assessed according to the Rectal Cancer Regression Grade (RCRG) system of Wheeler.Results:The growth curve of the tumor in experiment group showed the drop tendency, while the control group was significantly higher. The inhibitory rate of the experimental group was 89.24% and 94.77% after 17 and 34 days. Histopathological response to RCRG 1 grade level, compared with the control group was statistically significant differences (P<0.05).Conclusion:¹⁰³Pd has the remarkable lethal effect on the human gastric tumor xenografts in nude mice.Part II The influence to expression of Survivin,P53,PCNA on the human gastric tumor cell in nude mice after interstitial brachytherapy with ¹⁰³Pd.Objective:To investigate the effect of interstitial implantation with 103pd seeds in nude mice with the human gastric tumor through observing the expression of Survivin,P53,PCNA.Methods:The animal models of the human gastric poorly differentiated gland BGC-823 cell tumor were established first through the injection of the cells into nude mice subcutaneously, followed by the implantation of the palladium-103 granules into the tumor mass. The animals were divided into 2 groups randomly (experimental and comparison group,20 nude mice in each group), The ¹⁰³Pd seeds were implanted into the tumors according to the treatment plan defined by the computer three dimensional treatment planning system (TPS) in the experimental group, with a prescription dose of 120Gy and a seed activity of 2.96×107Bq. The comparison group was given the implantation with cold seeds. The expression of Survivin,P53,PCNA were detected by immunohistochemistry at the 17th day and the 34th day. The buffy masculine signal of Survivin located at nuclei and cytoplasm, while P53 and PCNA located at nuclei. Choosing 10 visual fields randomly, the tumor cells and the positive cell population was calculated. Results:The expression of Survivin,P53,PCNA of control group after 17 days was strong positive, the positive cell population was 72.76±13.69%,70.46±17.71%,82.30±3.55%;while treated group was weakly positive, the positive cell population was 42.67±13.37%,39.18±6.87%,62.74±6.77%,the difference was significant. The expression of Survivin,P53,PCNA of control group after 34 days was strong positive, the positive cell population was 63.74±6.77%,72.37±14.66%,81.94±5.39%;while treated group was weakly positive, the positive cell population was 15.53±5.85%,14.29±8.99%,38.96±7.46%,the difference was significant(P<0.05). There was statistically significant differences between two time also(P<0.05).Conclusion:The expression of Survivin,P53,PCNA stepped down after interstitial implantation with 103pd seeds in nude mice with the human gastric tumor, we can presume that the treatment related to restraining the cancer cell multiplication and inducing apoptosis.