Fanconi Anemia: Diagnosis and Treatment

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Since 5-20 % of solid tumors in the generalpopulation have a defect in the FA pathway,we would like to find targeted therapies forthese tumors.Used the principle of “Synthetic Lethality”
Screening Approach to Identify Gene Targets in FA Cells.FA CorrectedFA MutantDay 1Cells seeded400 Gene TargetsDay 2Each well transfectedwith siRNA oligonucleotideDNA repairsiRNA libraryDay 6 yMeasure Cell viability withATP-activated luminiscence(quantitative measure)
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Fanconi anemia history• Named aft
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Image courtesyDr Blanche Alter
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Image courtesyDr Blanche Alter
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Fanconi Anemia: Cellular phenotype
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Chromosome breakage read-outML# Ref
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The Fifteen Fanconi Anemia GenesGen
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The Fifteen FA proteins regulate DN
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BRCA2 is a Fanconi Anemia Gene (D1)
Page 26 and 27: In BRCA2 kindreds:dParadoxBRCA2 (+/
Page 28 and 29: Natural history of FA• Birth defe
Page 32 and 33: Pathophysiology• DNA repair Bone
Page 34 and 35: Treatment of Fanconi AnemiaAndrogen
Page 36 and 37: 100%90%Unrelated Donor BMT for FASu
Page 38 and 39: New treatments are badly needed•
Page 40 and 41: Alan D’AndreaJohn PostlethwaitMar
Page 42: mammary AC10 moovarian AC13 momamma
Page 45: Properties of tempol• Superoxide
Page 49 and 50: Conclusions• The SOD mimetic temp
Page 51 and 52: From:Maclean KH, Dorsey FC, Clevela
Page 53 and 54: Mean tumor-free survival:Placebo: 1
Page 57: Reduced numbers of stem cells
Page 60: Changes in cell cycle status of ste
Page 70 and 71: SRT3025 (“SirT Diet”) treatment
Page 72 and 73: Cancer Cells are often defective in
Page 74 and 75: Cancer Cells are often defective in
Page 78 and 79: siRNA Targets Specifically Toxic to
Page 80 and 81: FA Cell Lines Are Hypersensitive to
Page 82: Conclusions:1) Conventional cancer
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Fanconi Anemia: Diagnosis and Treatment

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