Oncology; Wound Healing; Cytokines

Front 1

most variable period of cell cycle, where growth factors act

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G1

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cell cycle period most sensitive to radiation therapy

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M

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why does radiation therapy cause delayed healing?

Back 3

impaired fibroblasts

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extremity sarcoma biopsy is excisional is < __ cm

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4

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Li Fraumeni syndome: mutation in

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p53 (tumor suppressor)

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Li Fraumeni syndome: tumors where?

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Sarcomas, breast CA, brain tumors, leukemia

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How do sarcomas spread?

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hematogenously (NOT to lymphatics)

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sarcoma: staging

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based on grade, not size or nodes

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c-myc mutation associatied with what cancers?

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Burkitt's lymphoma

neuroblastoma

small cell lung ca

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gene that regulates apoptosis, mutations associated with cancer

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bcl-2

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erb B: significance in breast cancer

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epidermal growth factor receptor. Associated with decreased survival in breast CA

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K-ras encodes for ____ protein

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GTPase protein (turns off signaling)

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K-ras mutations associated with what cancers?

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90% pancreatic ca

50% colon ca

also in lung cancer

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Ret proto-oncogene mutation diagnostic for ____ cancer

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medullary thyroid cancer

Front 15

Next step in treatment for pt with FH of MEN who has Ret mutation

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prophylactic thyroidectomy

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Ret is mutated in what disease?

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MEN 2

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MEN1 syndrome: sx

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tumors in PT gland, pancreas, anterior pituitary

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MEN2a syndrome: sx

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medullary thyroid cancer, PT tumors, pheochromocytoma

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MEN2b syndrome: sx

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medullary thyroid ca; pheo; marfanoid habitus

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Tamoxifen: indications

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partial estrogen agonist/antagonist.

Decrease breast cancer in high risk

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Tamoxifen: side effects

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endometrial ca

DVT

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Bleomycin and busulfan: complications

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pulmonary fibrosis

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levamisole: indication and MOA

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anthelminthic and immunostimulant

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cell responsible for healing by 2ndary intention

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myofibroblast. provides wound contraction from center of wound

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principal collagen in late scar

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Type I

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principal collagen in healing wound

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Type III

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collagen type ___ in basement membranes

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IV

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collagen type ___ in cartilage

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XI and II

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Collagen production begins day ___, max at day ____

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3;21

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increases strength of collagen

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crosslinking

Front 31

Type III collagen becomes Type I collagen with maturation when?

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around week 3

Front 32

Opening a wound of what age results in quicker healing the second time and why?

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5 days or older; due to cells and products already present

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What cells come to the wound in what order?

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platelets, PMNs, macrophages, fibroblasts (dominant by day 5).

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____ stimulates fibroblasts

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TGF-&beta;

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TGF-β is chemotactic for ____ and ____

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fibroblasts and neutrophils

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too much TGF-β causes what?

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too much fibroblast activity --> fibrosis (eg cirrhosis, pulm fibrosis)

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PDGF (platelet derived growth factor): what does it do?

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Attracts fibroblasts and increases smooth muscle to speed matrix deposition and collagen formation

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TxA2 comes from ______

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platelets

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TxA2: what does it do?

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causes platelet aggregation and vasoconstriction

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PGI2 comes from ____

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prostacyclin

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PGI2 : what does it do?

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Decreases platelet agg, causes vasodilation and bronchodilation

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Main source of TNF

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macrophage/monocyte

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most potent stimulus for TNF release

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endotoxin (LPS)

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TNF: moa of cachexia

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lipolysis, glycolysis, anorexia

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IL-1: what does it do?

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potentiates/is synergistic with TNF.

Responsible for fever (pyrogen)

Acts to increase IL-6 (acute phase response)

Increases endothelium adherence via selectins and ICAM and VCAM

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acute phase response: definition

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increase in certain protein concentrations in response to inflammation. Increases fever and catabolism. Increases CRP, amyloid, fibrinogen, haptoglobin, ceruloplasmin, &alpha;-1-antitrypsin

Decreased levels of albumin, transferrin, fibronectin

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acute phase response: decreased levels of what proteins

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Decreased levels of albumin, transferrin, fibronectin

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acute phase response: increased levels of what proteins

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CRP

amyloid

fibrinogen

haptoglobin

ceruloplasmin

&alpha;1-anti-trypsin

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CXC chemokines: what do they do?

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Chemotactic and important in angiogenesis and wound healing