Inducing Defferentiation Therapy On Xenograft Human Brain Glioma By Sodium Phenylbutyrate

tobjectivel In order to provide experimental evidences for clinical trials,proberd the doseage,treatment effects and reacting mechanisms about sodium phenylbutyrate(SPB) on bearing xenograf human brain glioma nude mice in vivo. [ntethodsj The 9th strain (low differentiation) was cloned from SHG-44 cell line, ampled in vitro,and was inoculated subcutaneously into the right flank of the nude mice quantitatively.When the solid tumors reached the size of 1cm3 of diameter, the turner was dissects into pieces of 0.3mn9 each, then inoculated to the nude mice. Then glioma xenograft models were established.When the tumor reached 0.5cm3,SPB treatment started. 50mg/kg SPB was injected peritonenlly once a day for three weeks continously in the 1st experiment. 100mg/kg SPB was injected peritoneally once a day for three weeks continously in the 2nd experiment. In the 3rd time, 300mg/kg SPB was injected peritoneally twice a day for four weeks continously in one group; In another group, 3mg/kg CDDP was injected poritoneally once a day for the first three days, then 300mg/kg SPB was injected peritoneally twice a day in the rest days subsiquently. The weight of tumors and mice was measured every 3 days with vernier caliper and balance respectively. When the experiment was over,xenograft tumor tssues were havested. Pathologic observation included HE staining and GFAP iminunohistochemistry. Iresultsl In the 1St experiment, animal models were established with tumor cells inoculation injection. The weight of tumors appeared considerable variably. Necrosis in large areas was observed on pathologic test. Weight loss of tumro-bearing mice were not found. In the 2nd experiment,tumer models were establised by inoculation with 0.3mm3 pieces of solid tumor. Tumors grew in a same manner. Bi4,there were no obvious effects of 100mg/kg SPB on tumors .Weight loss was not found; In the 3rd expriment, animal models were established by inoculation with 0.3mm3 pieces of solid tumor. Tumor cells?biologic propreity was stable relatively. Significant effect on tumor was observed in the group of 600mg/kg SPB . The effect included reducing and inhibiting tumor growth(P<0.001) .weight loss of tumor-bearing mice were not found; In combination therapeutic group, the same result was found, while there was no significant difference between the two groups (P>0.05). Toxic effects of CDDP was found in combination therapeutic group. Mice抯 weight declined about 20%, but gradually recoved when chemotheray was finished, so mice treated with SPB subsiquently. In control group,microscopilly tumor cells invaded muscles, ranged tightly, appeared bipolarly. Heteromorphosis and necrosis were apprent. (IFAP staining was positive; In SPB treatment group,cells ranged loosely, appears polyhedros is. Heteromorphsis is not apprent, Necrosis is not found. Nucleus was relatively small. Cytoplasm is rich. GFAP staining was significant positive. The difference between the two treated group was not significant. Tumors?growth relapsed when the drug was withdrew. Fconclusionsl 1. SPB had significant inducing differentiation effect on glioma ,which was dose dependent in certain dosage range.600mg/kg dose was suitable;2. SPB had no obvious toxity .Under maximum dose,the weight loss was not found yet.But rumor Cells did not reach terminal differentiation phase when treated by SPB. 3. CDDP had no synergetic effect with SPB;4.The biologic characteristics of nude mice solide tumor was...