| The incidence of hemogenous cerebral and meningeal metastasis is very high. 17%-80% patients suffered from tumor have metastatic lesions in different organs. Once it happens, the situation deteriorates quickly and high death rate may be caused. However, the mechanism of metastasis is still unknown. The internal signal transduction, genetic mutation and the inactivation of anti-oncogene et.al may be invovled. Besides, the angiogenesis of tumor also attribute to metastasis. We have set up the hemogenous cerebral and meningeal metastasis animal model in rabbit. Several experiments have been conducted to investigate the anti-tumor effect of VEGF monoclonal antibody and we try to provide reliable early-phase diagnostic principles of metastatic tumor using magnetic resonance imaging . The study includes two parts:PART I Materials, methods and animal modelsVX2 CarcinomaIt is a virus-induced rabbit papilloma. In 1940, Kidd and Rous found a kind of squamous carcinoma derived from rabit papilloma can easily grow in rabbit skeleton muscles. Since then, it lost the virus-dependency and become stable and ready to grow in rabbit. VEGF MabProvided by Wuhan Boster Biological Technology Co.Ltd Establishment of animal modelNew Zealand white rabbits weighted 1.9-3 .Okg rendered by Animal Experiment Center, FMMU, were adopted. Anesthetized by 0.3% sodium pentobarbital 1 ml/kg .iv, with the neck hair-removed and sterilized, the rabbit was put onto the operation table. Cut open the skin, delaminated the soft tissues and exposed the common carotid artery(CCA). Puncture the CCA and inject 20% manna sugar 5ml/kg to ope the BBB. 10 minutes later, the VX2 cells were injected into CCA with the concentration 108/ml. Press for 10 minutes to stop bleeding and suture the incision. A week later, MRI plain scan and enhanced scan were performed to probe the growth of the intracranial tumor. MRI plain scan and enhanced scanWe have Siemens 1.5 Tesla super-conducting Magnetic Resonance Imaging system. Using knee coil and SE sequence with FOV 130 x 130mm, we had the rabbit head axial surface and coronal surface scanned. The scan parameter: TiWI(TR 350MS, TE90MS), T2WI(TR2300MS, TE90MS), Lamina Thickness 4mm. After administration of Gd-DTPA, TiWI scan was performed with the same parameter as before.Immunohistochemistry stain and mean grey density assayAfter the last MRI examination, the rabbits were put to death and the intracranial tumor tissues were obtained to be immunohistochemistry stained. The image analyzer(Ommicon Fas-Ill, made in Germany) composed of a microscopic photographic system and a computer gave the data of mean grey density.PART II Experimental study of the VEGF monoclonalantibody effect in rabbit modelMethod:We had 7 groups and 6 rabbits in each group. The rabbits in l-5groups received VEGF MAB administration with the dosage 25 ju g, 50 ja g, 100 ju g, 150 ju g, 200 (a g respectively at the same time the VX2 cells were injected. The rest 2 groups were control groups, one group injected natural saline and the other injected only VX2 tumor cells. All rabbits should have MRI plain and enhanced scan 7ds 9d> 1 ld> 13d, 17d, 2Id respectively after operation.Results:1. MRI enhanced scan detected more metastatic lesions than that by plain scan in every period of time(P<0.01).2. The 100 M g, 150 ja g, 200 ,u g Mab administrated groups had more metastasis than that of the control group(P<0.01) while the 25 |a g, 50 |a g group had no difference from the control.3. The lesions of 100 ja g, 150 ja g, 200 ja g groups were smaller than that in control group(P<0.01) and the growth rate slower than that in control. The 25 ja g, 50 ja g group presented no difference from the control.4. The mean grey density of tumor tissues were 192.05 while the normal brain tissue 204.72, differed significantly(P<0.01). The MG of tumor tissues in 1-5 groups had no difference from that of control.5. The cerebral and meningeal metastasis of VX2 tumor has prominent characteristics in MRI... |
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