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Summary: giant cell tumor of bone

Summary: giant cell tumor of bone. Safety and efficacy of denosumab for giant cell tumor of bone What have we learnt, and where to from here?. Summary: chondrosarcomas.

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Summary: giant cell tumor of bone

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  1. Summary: giant cell tumor of bone • Safety and efficacy of denosumab for giant cell tumor of bone • What have we learnt, and where to from here?

  2. Summary: chondrosarcomas • GDC-0449 in patients with advanced chondrosarcomas: a French/US and French National Cancer Institutes Phase II collaborative study (Italiano) • Outcomes of inoperable central chondrosarcoma (Picci) • SRC signaling is involved in chemoresistance and migration of chondrosarcoma cells (van Oosterwijk)

  3. POSTER: MTORC1 inhibitor targets SRC oncogenic signaling via MIRs in human chondrosarcoma • PRP1 (an MTORC1 inhibitor) targets SRC via upregulation of MIR181A/99A/450A/199b5b • SRC downregulates these MIRs • MIR99A regulates MTOR/FGFR3 • Complex feedback loops involving RAS/MAPK and PI3K pathways • PRP1 has cytostatic effects Galoian, Temple

  4. Galoian, Temple

  5. Summary: chordoma • High-dose single fraction radiotherapy for the management of chordomas of the spine and sacrum (Yamada et al) • Germline polymorphisms in brachyurychordoma risk (Flanagan et al) • The landscape of mutations in chordoma: PIK3CA and epigenetic modifiers (Campbell)

  6. POSTER: HDAC inhibitor (Panobinostat) effects on mesenchymal tumors and chordomas • Panobinostat inhibits growth of chondrosarcoma line JJ012 • No effect on chordoma lines • Effects independent on effects on ubiquitin ligase pathway • Suggest combinations with other agents where resistance exists Galoian, Temple

  7. Galoian, Temple

  8. Galoian, Temple

  9. HIF-1 Signaling in Chordoma is Identical to Nucleus Pulposus and Confers Survival Advantage in Hypoxic Environment John A Abraham, MD 1 Francis J Hornicek MD PhD 2 Irving Shapiro PhD 1 MakarandRisbud PhD 1 1Rothman Institute at Thomas Jefferson University Philadelphia, PA 2Massachussetts General Hospital Boston, MA

  10. HIF-1 Signaling in Chordoma is Identical to Nucleus Pulposus and Confers Survival Advantage in Hypoxic Environment • Hypothesis: • Chordoma is embryologically similar to nucleus pulposus cells • HIF-1 is an important factor in protecting NP cells from apoptosis in the hypoxic conditions in which they reside. • The purpose of this study was to determine if a similar mechanism could be functioning in Chordoma cells. • Summary of Findings • Chordoma and NP cells show identical patterns of HIF-1a expression under normoxic and hypoxic conditions, unlike cells derived from most other tissues • Transcription of HIF-1 in both Chordoma and NP increases significantly in hypoxic conditions • Hypoxia protects NP cells from apoptotic stimuli. Serum starvation under hypoxic conditions produces significantly less apoptosis that under normoxic conditions • Discussion • HIF-1 is likely a key factor in Chordoma cell survival under hypoxic conditions. • Interruption of HIF-1 signaling may be a therapeutic mechanism

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