A Basic Study On The Biodegradable Nanonpolymer Administered Taxol For Intratumoral Local Chemotherapy Of C₆ Gliomas In The Rat

There are nearly 44% of intracranial malignant tumors are gliomas. Thetreatment about glioma continues challenge neurosurgeons. At present, theconventional treatments of glioma are surgery, radiotherapy and chemotherapy.Operations can not totally remove this kind of invasive malignant tumors.Traditional radiotherapy can't advoid brain edema because of cytonecrosis. localchemotherapy play an significant role in clinical if the tumor local indeeply ,perhaps the tumor who infringe upon important function area, the risk ofsurgical is so big that total remove the tumor tissue is impossible , if these tumorare medicine sensitive, should even use the chemotherapy treatment as the firstchoose. In recent years, the research that induces the tumor apoptosis and itsmechanism becomes the anti-malignant tumor research of a little bit hot. Theresearch that induces the tumor cell apoptosis to the taxol has already openned anexhibition extensively as well. It was observed that the tumor cell lives in cultureor living body and the normal organization will appear the cell apoptosis veryquickly after be subjected a certain dose of taxol, but the mechanism of theapoptosis and haven't yet known very well. Recently someone believe that thetaxol can induce a series of gene expression or adjust under some geneexpressions or close of cell. after the membrane signal to aim system activate,make the cell take place apoptosis.biodegradable nanofiber polymer administered taxol for intratumoral ortransplant tumor chemotherapy keep on send out medicine make the tumor cellto be killed, and normal cell has small harm only.there are rare report on thiskind of research about the mechanism of local chemotherapy.This study contains following work:1. The cytotoxicity experiment about nanonfiber polymer: outside method2. The biodegradable nanonfiber polymer administered taxol to the rat brainmalignant glioma C6 cell's propagate be repressed and induce the cell apoptosisin culture3. The establishment of the stereotactic Wistar rat C6 brain glioma animalmodel.4. Study the contribution of biodegradable nanonfibre polymer administeredtaxol local chemotherapy the rat bearing glioma on the basis of the model,Biodegradable nanonfibre polymer administered taxol inducement apoptosis andinfluence of the genes in the process of the treatment.the gene chip examinationgene transform in this process.discover the apoptosis function and mechanismabout biodegradable nanonfibre polymer administered taxol intratumor localchemotherapy to C6 glioma cell in Wistar rat5. The RT-PCR examines C-myc, Bcl-2, p53, the p is 16 expression of thegenes.After these study (outside and inside of the bodies) we can usebiodegradable nanonfibre polymer administered taxol to the patients bearingglioma in the future provide the theory basis.The main result of this study as follows:1. the observation on the C6 cell's appearances indicate that after treatmentwith the biodegradable nanonfibre polymer administered taxol , C6 cell arrangesparse, the size and appearances of the cell incline to consistently. The cellnucleu comparison the cytoplasm diminish (2) Cell's counting method, MTTmethod confirmation the biodegradable nanonfibre polymer administered taxolexist time, dosage dependence on repress the C6 cells. (3) The FCM indicate therate of apoptosis raise obviously.2. The achievement ratio about establishment of the stereotactic Wistar ratC6 brain glioma animal model is 86%, the average existence time is 20.6±3.6days, the tumor GFAP dye masculine, the HE dyes manifestation tumor to growgradually, but with normal brain the still has a boundary. Have no growth outsideof brain or in the other side brain, the model is stabilize and credibility.3. After local chemotherapy with biodegradable nanonfibre polymeradministered taxol,the rat exists time is 56.5 ±18.7 days, 2 rat the survival isover 70 days.The MRI manifestation the tumor contract. Organize the pathologycheck sees the control's tumor diameter 6.5±0.7mm, the drug's group tumordiameter as 4.5 ± 0.4mm.Showing the biodegradable nanonfibre polymeradministered taxol repress tumor propagate.4. Biodegradable nanonfibre polymer administered taxol inducementapoptosis and influence of the genes in the process of the treatment.the gene chipexamines about 27000 genes totally.2 brain tissue (normal rats and the tumor)diffet expression genes distinguish to 310 and 324, gene C-myc (Ratio 2.37),bcl-2 (Ratio 3.25), p53 (Ratio 0.43), p16. (Ratio 0.21). The difference expressiongene disti -nguishes is 351 and 339s in 2group(tumor and the drug group),C-myc (Ratio 0.35), bcl-2 (Ratio 0.26), p 53 (Ratio 2.21), p 16. (Ratio 3.06)5. The RT-PCR examines C-myc, Bcl-2 visibleto descend, p53, the p16expression visibleto raise in the protein level and the mRNA level aftertreatment.The main conclusion of this study:1. The biodegradable nanonfibre polymer administered taxol exist time,dosage dependence on repress the C6 cells.2. The biodegradable nanonfibre polymer administered taxol fasten the C6cells induced the apoptosis function. The C0/G1 period cell increment in thisprocess, the S period descend.3. The established stereotactic Wistar rat C6 brain glioma animal model. isstabilize and credibility.4. The rat existence period extension after chemotherapy with thebiodegradable nanonfibre polymer administered taxol the tumor contract, theapoptosis cell increment.5. The gene chip examines about 27000 genes totally.2 rats are normal thebrain organize to organize the difference expression gene with the matchedcontrol tumor to distinguish to 310 and 324s, 2 matched control tumororganization and processing difference in set expression the gene distinguish to351 and 339.the RT-PCR examination shows the gene C-myc, Bcl-2 down, butp53, p 16 gene expressions strengthenin the protein and mRNA level.Creative of this research:Prove biodegradable nanonfibre polymer administered taxol repress C6propagate outside the body, induce the apoptosis.its mechanism possibilityrelevant. With C-myc, Bcl-2 repress and p 53, p16 genes activate the Wistar ratC6 glioma animal model stability credibility, can satisfy the demand of theglioma experiment research.These studys (outside and inside of the body) biodegradable nanonfibrepolymer administered taxol local chemotherapy C6 gliomas be in conjunctionwith relevant.gene induce the tumor cell apoptosis...