Also, pretreatment with T oligos substantially prolonged the survival time from the animals intracranially inoc ulated by malignant glioma cells compared together with the untreated and manage oligonucleotides treated groups. These results indicate that T oligos are a promising agent to treat malignant gliomas by stimulating the induction of non apoptotic autophagic cell death. ET 04. Targeting GLIOBLASTOMA With a NEW CLASS OF SELECTIVE Minor MOLECULE HIF INHIBITORS Vladimir E. Belozerov,one Taku Narita,1 Jiyoung Mun,two Rita Noronha,three Hui Mao,2 Saroja N Devi,one Mark Goodman,2 Kyriakos C. Nicolaou,three Ruiwen Zhang,four and Erwin G. Van Meir1, 1Department of Neurosurgery Hematology/Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA, 2Department of Radiology, School of Medicine, Emory University, Atlanta, GA, USA, 3Department of Chemistry, Scripps Research Institute, La Jolla, CA, USA, and 4Cancer Pharmacology Laboratory, University of Alabama at Birmingham, Birmingham, AL, USA Hypoxia is known as a frequent function of brain tumors that build as the tumor mass outgrows the current vascular provide.
Intratumoral hypoxia strongly contributes on the malignant phenotype of brain tumors by improving angiogenesis, migration, and clonal variety of mutations in anti apoptotic genes and sustaining an undifferentiated state of cancer stem cells. Even more, hypoxic regions of your tumor are resistant to traditional chemotherapies PI-103 clinical trial and radiotherapies, for this reason, they signify a significant therapeutic target. HIF 1 can be a major transcription component that orchestrates a variety of adaptive molecular responses, allowing cancer cells to survive and proliferate inside a hypoxic surroundings. Our laboratory and other individuals have shown that the reduction of HIF 1 levels in cancer cells drastically slows down tumor growth in vivo.
These findings are the basis for our efforts to charac terize and create certain modest molecule inhibitors of HIF 1. Not long ago, we screened a combinatorial library of natural products like compounds working with a cell based assay for HIF activity and identified a new class of selective HIF 1 inhibitors. Our research propose that the lead inhibitor of this class, KCN1, Salicin potently minimizes hypoxic levels of HIF 1A in gli oma cell lines whereas exerting minimal results on other quick lived proteins, HIF 1B, and manage proteins. Further, the action of KCN1 appeared to be independent from the activation state of big signal transduction pathways. Evidence addressing the molecular mechanism of KCN1 will likely be presented. Our preliminary animal experiments recommend that KCN1 inhibits HIF one signaling in tumor xenografts and accumulates in orthotopic

brain tumors, provid ing the basis for more in vivo scientific studies.