Der „Basalzellenkrebs“E. Krompecher, 1903
1894                   TodayIllustration P.G. Unna   Photography W. Neuse
1895                     TodayIllustration G. Thibierge   Photography W. Neuse
BASAL CELL CARCINOMA                  INCIDENCEAustralia    up to 2 % per yearUSA          White population      407 / 100...
BASAL CELL CARCINOMA               RISK FACTORSSkin type I – IIIonising radiationBurnsAs, Tar, SmokingImmunosuppressionAge...
BASAL CELL CARCINOMA          AND IONIZING RADIATIONMultiple BCCs 20 yrs after irradiation of Hodgkin´s disease
BASAL CELL CARCINOMA    DISTRIBUTIONHead/Neck      60 %     Nose      14 %Trunk          30 %Extremities    10 %
BASAL CELL CARCINOMA                  PATHOGENESIS                      UV Immuno-                              DNASuppres...
NEVOID BASAL CELL CARCINOMA-          SYNDROME (NBCCS)Autosomal dominantMultiple BCCs at young ageSkin, CNS, Skeletal invo...
THE SONIC HEDGEHOG PATHWAY Shh                     extracellular Ptch    Smoh                     intracellular           ...
PTCHHuman homolog of the Drosophila - Gene patched            Wild type          PTCH MutantDrosophila: segmental developm...
ANALYSIS OF SHH PATHWAY GENES          IN SPORADIC BCCs   PTCH mutations:                            28/42 (67%)   SMOH mu...
PTCH+/- MOUSE MODELModel of human NBCCSBody size increasedMedulloblastomas (15%)                           Medulloblastoma...
„MOUSE SOLARIUM“
GDC-0449SMALL MOLECULE SMO-INHIBITOR
von Hoff et al., N Engl J Med 2009
PHOTODYNAMIC THERAPY (PDT)                          PDD with                         Wood-LightTopical application of     ...
PHOTODYNAMIC THERAPY           OF NBCCSBefore therapy      After 4x PDT
FLUORESCENCE DIAGNOSISPre-operative determination of tumor margins
And I told him,put some cream on
UV PROTECTION
OBC | New development in the therapy of basal cell carcinoma
OBC | New development in the therapy of basal cell carcinoma
OBC | New development in the therapy of basal cell carcinoma
OBC | New development in the therapy of basal cell carcinoma
OBC | New development in the therapy of basal cell carcinoma
OBC | New development in the therapy of basal cell carcinoma
OBC | New development in the therapy of basal cell carcinoma
OBC | New development in the therapy of basal cell carcinoma
OBC | New development in the therapy of basal cell carcinoma
OBC | New development in the therapy of basal cell carcinoma
OBC | New development in the therapy of basal cell carcinoma
OBC | New development in the therapy of basal cell carcinoma
OBC | New development in the therapy of basal cell carcinoma
OBC | New development in the therapy of basal cell carcinoma
OBC | New development in the therapy of basal cell carcinoma
OBC | New development in the therapy of basal cell carcinoma
OBC | New development in the therapy of basal cell carcinoma
OBC | New development in the therapy of basal cell carcinoma
Upcoming SlideShare
Loading in …5
×

OBC | New development in the therapy of basal cell carcinoma

837 views

Published on

Thomas Ruzicka, LM University of Munich, Germany
New development in the therapy of basal cell carcinoma

http://obc2012.outofthebox.si/

0 Comments
0 Likes
Statistics
Notes
  • Be the first to comment

  • Be the first to like this

No Downloads
Views
Total views
837
On SlideShare
0
From Embeds
0
Number of Embeds
3
Actions
Shares
0
Downloads
15
Comments
0
Likes
0
Embeds 0
No embeds

No notes for slide

OBC | New development in the therapy of basal cell carcinoma

  1. 1. Der „Basalzellenkrebs“E. Krompecher, 1903
  2. 2. 1894 TodayIllustration P.G. Unna Photography W. Neuse
  3. 3. 1895 TodayIllustration G. Thibierge Photography W. Neuse
  4. 4. BASAL CELL CARCINOMA INCIDENCEAustralia up to 2 % per yearUSA White population 407 / 100 000 / year 1 million cases in 2005 Half of all cancers 80 % of all NMSCWorldwide Increasing incidence
  5. 5. BASAL CELL CARCINOMA RISK FACTORSSkin type I – IIIonising radiationBurnsAs, Tar, SmokingImmunosuppressionAge > 60Previous BCC: RR 10xGene mutationsUltraviolet !
  6. 6. BASAL CELL CARCINOMA AND IONIZING RADIATIONMultiple BCCs 20 yrs after irradiation of Hodgkin´s disease
  7. 7. BASAL CELL CARCINOMA DISTRIBUTIONHead/Neck 60 % Nose 14 %Trunk 30 %Extremities 10 %
  8. 8. BASAL CELL CARCINOMA PATHOGENESIS UV Immuno- DNASuppression Mutations Repair BCC Genetic Skin type Predisposition
  9. 9. NEVOID BASAL CELL CARCINOMA- SYNDROME (NBCCS)Autosomal dominantMultiple BCCs at young ageSkin, CNS, Skeletal involvementPredisposition to malignancy(medulloblastoma)PTCH germ line mutations
  10. 10. THE SONIC HEDGEHOG PATHWAY Shh extracellular Ptch Smoh intracellular PTCH Gli1/2 HIPSufuh CCNB1/D2 Gli1/2 FOXM1/FOXE Nucleus BCL2
  11. 11. PTCHHuman homolog of the Drosophila - Gene patched Wild type PTCH MutantDrosophila: segmental developmentFunction: Receptor for the hedgehog protein Tumor suppressor
  12. 12. ANALYSIS OF SHH PATHWAY GENES IN SPORADIC BCCs PTCH mutations: 28/42 (67%) SMOH mutations: 4/42 (10%) SUFUH mutations: 2/42 (22%) GLI1/GLI2 overexpression: 42/42 (100%)In 70% of BCCs somatic mutations of Shh genesShh pathway is constitutively activated in all BCCs Wolter et al., Cancer Res 57: 2581-2585, 1997 Reifenberger et al., Cancer Res 58: 1798-1803,1998 Reifenberger et al., Br J Dermatol: 43-51, 2005
  13. 13. PTCH+/- MOUSE MODELModel of human NBCCSBody size increasedMedulloblastomas (15%) MedulloblastomaBCCs after repetitive UVB exposure UVB induced BCCs
  14. 14. „MOUSE SOLARIUM“
  15. 15. GDC-0449SMALL MOLECULE SMO-INHIBITOR
  16. 16. von Hoff et al., N Engl J Med 2009
  17. 17. PHOTODYNAMIC THERAPY (PDT) PDD with Wood-LightTopical application of 417 nm PDT withALA 20 % (3 - 5 h) red light 634 nm
  18. 18. PHOTODYNAMIC THERAPY OF NBCCSBefore therapy After 4x PDT
  19. 19. FLUORESCENCE DIAGNOSISPre-operative determination of tumor margins
  20. 20. And I told him,put some cream on
  21. 21. UV PROTECTION

×