1. Oral Mucositis in Cancer Care: Is The End in Sight? Peter B. Lockhart, DDS, FDS RCPS Chair, Department of Oral Medicine Carolinas Medical Center

3. Absolutely Doubtful No way Possibly Never Perhaps Likely Yes Could be No

12. Chemotherapy Stomatotoxicity 1978 - 1988 Direct Indirect Bleeding Decreased nutrition Mucosal infection Cell renewal Thinning Mucositis and ulceration Thrombocytopenia Neutropenia Xerostomia

14. Trauma – Dentures

15. Concomitant Chemotherapy and RT

16. Trauma – Teeth and Restorations

20. Atrophy and Collagen Degeneration

21. Mucosal Sloughing

23. Mucositis Study Group International Society for Oral Oncology (ISOO) 1985 Multinational Association of Supportive Care in Cancer (MASCC) 1995

24. Mucositis Pathobiology and Practice Guidelines - 2004 © MASCC 2004 Cancer Supplement May 1, 2004

25. DNA damage and apoptosis Reactive oxygen species (free radicals) Mucositis, damaged cells, blood vessels Mechanism – Current Thinking

26. Today’s Pathobiology Perspective: A Multiple Mechanism Model Healing Ulceration Signaling and Amplification Upregulation and Message Gen Initiation Keefe and Sonis – Cancer Supplement. 100:1995-2011, 2004.

27. Today’s Pathobiology Perspective: A Multiple Mechanism Model Healing Ulceration Signaling and Amplification Upregulation and Message Gen Initiation Apoptosis Tissue Injury IL-1  TNF-  IL-6 NF-  B Angiogenesis Clonogenic Cell Death ROS DNA Injury Fibronectin Breaks Up Activates Macrophages MMP Gene Upregulation Cell Membrane Epithelium Endothelium Connective Tissue Macrophages Sphingomyelinase Ceramide Pathway Ceramide Synthase Expression of Adhesion Molecules COX-2 CT RT

28. Feb. 2007

45. Gram-negative Bacteria and Oral Mucositis G (-) bacilli Lipopolysaccharide release Binding to epithelium Cytokine release: TNF, IL-6, IL-1 Increased inflammatory process

48. Culture Independent Methodology Bacterial isolate PCR of 16S rRNA TOPO TA cloning kit E. Coli 16S rRNA library (24-25 clones) DNA sequencing Species identification