We established no matter if mL2G7 therapy alters the downstream targets of c Met activation, phospho MAPK and phospho AKT, concurrent with tumor growth inhibition. Mice bearing pre established subcutaneous U87MG glioma xenografts had been treated with I. P. injections of mL2G7 each and every alternate day for 3 days. Tumors regressed by 70% above this quick therapy time period. Using a semiquantitative immunob lot evaluation, we found inhibited phosphorylation of phospho/total AKT and phospho/total MAPK in mL2G7 handled tumors. These findings suggest that systemic neutralizing anti HGF monoclonal antibody inhibited the growth of HGF expressing gliomas by downregulat ing AKT and MAPK dependent signal transduction pathways downstream of c Met. ET 24. ANTI ANGIOGENIC TARGETED Treatment Inside a RAT MODEL FOR GLIOBLASTOMA MULTIFORME TUMOR WITH TEMPORAL MRI AND PET Research Michael Lim, Yi Shan Yang, Leroy Sims, Steven Choi, Yingyun Wang, and Samira Guccione, Stanford University, Stanford, CA, USA We have now created an anti angiogenic method that kills tumor neo vasculature.
This method inhibitor VER 155008 is definitely an integrin targeted delivery system which could carry chemotherapy, radiation, or genes for the tumor vasculature. Within this presentation, a gene was delivered towards the tumor endothelium that leads to VEGF or FGF activated endothelial cells to apoptose. We examined the efficacy of NPTx on the selection of tumor models, such as the RT2 primary brain tumor model in rats. Tumors were initiated by stereotactic injection from the RT2 cells to the striatum of F344 rats. After confirming the presence from the tumor mass with MRI, we handled rats with our integrin targeted therapeutic. Treatment was fractionated over 3 days with intra venous injection of NPTx. FDG PET and MRI scans were utilized to follow up the handled and untreated animals.
All control animals died of mass results in much less than 28 days. Treated animals survived beyond 1 year after therapy, without any signs of recurrence, as determined WAY-600 by FDG PET, MRI, or histologic evaluation. Temporal evaluation within the program of remedy working with practical imaging supplies an productive strategy for early detection of response to treatment. The vascular delivery platform we’ve produced combines

effective targeting of therapeutics in the tumor and potent, selec tive destruction from the tumor endothelium. The resulting combined effect of this approach leads to significant tumor mass reduction. Recurrence or drug resistance has not been observed with this method thus far. Anti angiogenic therapies that destroy the tumor neovasculature can be an effec tive therapeutic technique for vascular tumors such as GBM. We are cur rently conducting toxicity research to evaluate NPTx for clinical translation, some of these toxicity results will be presented here.