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29 Cards in this Set

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What stage of wound healing do we see PDGF and TGF-ß1 (transforming growth factor)?
Epithelialization
Which stage of wound healing do we see VEGF ?
angiogenesis
Which stage of wound healing do we see Fibrinogen --> fibrinogen?
Break in skin (clot formation)
Which stage of wound healing to we see MMP and reorganization of the ECM?
Wound closure
Which cells produce TGFß1, TGF-∂ PDGF-AB, PDGF-BB, FGF and VEGF?
Platelets: TGFß1, and PDGF-AB… 2) Macrophages: VEGF, TGF-ß1/∂, PDGF-BB, and FGF… 3) Endothelial cells: VEGF and FGF
None
What is Avastin approved use in Rx? What does it also work on?
CRC… Macular degeneration
What is avastin mechanism of action?
Anti-VEGF mAB
None
What is the difference between Avastin (Bevacizumab) and Lucentis?
Lucentis is second generation Avastin… both are mAb against VEGF, but Lucentis is humanized (thus produces less inflammatory reponse), and is affinity maturized
Which, Avastin (Bevacizumab) and Lucentis, has the Fc region?
Avastin
what is the pathway for GF (mitogen) to activate Myc genes?
Mitogen binds (TKR) --> RAS --> MAP kinase --> Myc gene transcription
Name the 3 different ways, Myc can activate E2F.
1. Increased Cyclin-D activity --> G1/S-Cdk activation --> Rb phosphorylation --> increased E2F activity…

2. Increased p27 degradation --> G1/S-Cdk activation --> Rb phosphorylation --> increased E2F activity…

3. Increased E2F synthesis --> inceased E2F activity
None
What is p27?
A Cdk inhibitor
What does E2F activity lead to?
entry of cells from G1 into S-phase
Is Myc a tumor suppressor or pro-oncogene?
pro-oncogene
What is the mechanism of action of Becaplermin (Regranex gel)?
since the PDGF-BB TKR crossphosphorylate by dimerization, Becaplermin is two ligands covalently bound and thus causes dimerization
What does Becaplermin effective in binding and what is it used for?
PDGF-BB.. Used for diabetic ulcer care
What is the best practice for diabetic ulcer?
debridement and Becaplermin (@ higher dose: 100 ug/g)
what are the theoretical side effects of engineered growth factors used in wound healing?
malignancy and hypertrophic scars
What is an isozyme of an enzyme?
polymorphisms for metabolizing drugs in different people.
What two isozymes are of therapeutic value?
1. The enzyme the converts the prodrug into an active drug… 2. The enzyme that converts an active drug into an inactive metabolic derivative.
In CPT-11 (Irinotecan) which is a prodrug, certain patients have less activity in the enzyme that converts the active drug into an inactive metabolite, However, the metabolite (SN-38) is toxic at high dose and causes diarrhea and leukopenia. What do you do for those patients?
Reduce the dosage
Platinum compounds damage DNA. What mechanism repairs this damage?
Nucleotide excision repair
Which DNA repair mechanism is used to fix Xeroderma pigmentosum? (UV damage, oxidative damage and cross-links)
Nucleotide excision repair
What polymorphism do people with group D protein XPD (Xeroderma pigmentosum-D) have?

What does this polymorphism cause?

What is the faulty repair mechanism associated with XP?
1. polymorphism at 312 and 715…

2. Decreased response to 5-FU/oxaliplatin

3. Nucleotide Exclusion repair
Arrested for 5-FU discount by the XPD
What are the 4 stated steps of wound healing physiology, starting from and including a break in the skin?
1. Break in the skin (clot formation) … 2. Epithelialization… 3. Neoangiogenesis… 4. Wound closure
Which step of wound healing includes metabolic signals (need for oxygen and nutrients) VEGF?
Angiogenesis
Which step of wound healing includes degradation of ECM, Proliferation of epidermal cells, and PDGF and TGF-ß1?
Epithelialization
What step of wound healing includes fibrinogen --> fibrin (fibrin clot), inflammation, and platelet infiltration?
Break in skin barrier (clot formation)
What step of wound healing includes Reorganization of the ECM, MMPs secreted by macrophages, endothelial cells, fibroblasts, and epithelial cells in the context of signal transduction?
Wound closure