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Flashcards in Oncology - Sheet1 Deck (198):
1

Epidemiology of Cancer

Epidemiology of cancer

2

Epstein Barr virus

Burkitts lymphoma

3

human papillomavirus

cervical cancer

4

Hepatitis B virus

Liver cancer

5

Human T-cell lymphotrophic virus

Adult T cell leukemia

6

Kaposi's sarcoma- associated herpes virus

Kaposi's sarcoma

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pleomorphis

nucleus becoming more irregular in shape

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2 distinctions of malignant tumor

infiltration of surrounding normal tissue and metastasis

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Epithelial origin malignant

carcinoma

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epithelial originan benign

papilloma, adenoma

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mesenchymal origin malignant

sarcoma

12

mesenchymal origina benign

fibroma, lipoma

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hematopoietic origin malignant

lymphoma, leukemia

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well differentiated =

benign

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undifferentiated =

malignant

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carcinoma in situ

pre-invasive cancer. dysplastic changes in full epithelium but no invasion

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6 initial cancer hallmarks

growth factor independence, no response to anti-growth, resistance to apoptosis, limitless replicative, recruitment blood, invasion and metastasis

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PI3K

kinase involved in intracellular signaling

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PI3K function

converts PIP2 to PIP3

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What activates PI3K

various receptor tyrosine kinases including EGF

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PIP3 function

docking site for plecksrin homology domains. Main function is activation of AKT

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Warburg effect

high glycolytic rate in many cancer cells

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AKT ajor effect

increases glucose transport and glycolysis = warburg effect

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PTEN

antagonist to PIK3, dephosphorylates PIP3

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Li-Fraumeni syndrome

only one germ-linke copy of p53 so succeptible to a number of cancers. Loss of Heterozygosity

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p53 regulates

p21, GADD45, Bax,puma,noxa, DM2

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p21

cyclin/CDK inhibtor. cell cycle arrest

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CGADD45

DNA repair pathways protects genome

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Bax, Puma, Noxa

pro-apoptotic protein inducing cell death

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MDM2

ubiquilates p53, for degredation

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ATM, ATR, CHK2

activators of p53

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what transcribes MDM2

p53 transcribes it - form of negative feedback inhibition

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Two protein classes important in apoptosis

caspases and nucleases

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Caspase basic mechanism

use conserved cystein to cleave after aspartate. Makes the CASP part.

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Intrinsic apoptotic pathway

cytochrome c binds Apaf-1 recruits initiator procaspase 9

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cytochrome c

molecule in mitochondria critical for intrinsic apoptotic pathway

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caspase 9 activates

initiator caspase activating 3,6,7 for execution

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Cytochrome C release promoters

Bax and Bak

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Cytochrome C release inhibit

Bcl-2 inhibits BAK pore formation

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BAK function

sits in outer membrane to make pores.

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BAX function

when activated goes to BAK and helps make a pore

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Extrinsic pathway

Fas receptor activated by FasL. Recruits FADD - procaspases8 or 10 - caspases 3,6,7

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Fas receptor

death signaling receptor responding to FasL

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FADD

Fas associated death domain protein recruiting initator caspases

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Family of death receptors

DR4,5 TNFR1, DR3

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hTERT function

can surpress senescence of human cells. it extends and stabilizes chromosomes

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breakage fusion bridge cycles

cycles that occur with no telomeres involving DNA damage

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VEGF

stimulates EC division, master regulator of antiogenesis. VEGF-A most prominent

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VEGF activates

specific receptor tyrosine kinases on ECs

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Avastin (bevacizumab)

antibody against VEGF. late stage colon and renal cancer

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Sunitinib and sorafenib

small molecule based inhibitors. block VEGFR2

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seed and soil concept

cancer will lodge in areas that have appropriate growth factors for it to survive

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Avastin problem

successful inhibition of VEGF makes tumor more invasive and metastatic

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Cancer Diagnostics

Cancer Diagnostics

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philadelphia chromosome

translocation from 22 to 9

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philadelphia chromosome encodes

BCR-ABL

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BcrABL

has abnormal tyrosine kinase activity

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FFPE

formalin fixed paraffin embedded

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Imatinib

Prevents ADP bidning to CL enzyme

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BRAF mutation

40-60% of melanoma lesions. mutation predicts response to vemurafenib. most common mutation = V600E

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BRAF in papillary thryoid carcinoma

benign never have mutation. 40-70 have mutation

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BRAF in colorectal

predicts poorer prognosis

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Ilumina sequencing

real time sequencing by synthesis

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Sequencing read length

nuber of sequential images taken

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sequencing read depth

number of DNA fragments sequenced for any position

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One test at a time paradigm

only test for utation in cancers where it is signifiant and has a certain rate

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bcr abl hallmark

growth-factor independence

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Leukemai vs Lymphoblast

Leukemia generally of cells native to marrow. generally more immature cells

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acute neoplasm

early undifferentiated state

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chronic neoplasm

mature, differentiated states

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germinal center B cell markers

CD10+, BCL6+, BCL2-

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Mantle B cell markers

CD10-, BCL6-, BCL2+

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CD 21 marker

follicular dendritic meshwork

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Burkitt lymphoma translocation

t(8:14). overexpress MYC

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Follicular lymphoma translocation

t14:18 overexpress BCL2

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reason for more B cell NHL

because B cells go through multiple rounds of genetic rearrangement

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Small B cell NHLs (3)

SLL/CLL, Follicular lymphoma, marginal zone lymphoma

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FL common organ involvement

Spleen and liver. Rarely to bone marrow

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FL pathology

centrocytes and centroblasts. follicles close together

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centrocytes

small, cleaved low grade germinal center B cells

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centroblasts

large transformed noncleaved germainl b cells

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FL bone marrow growth

grows in a paratrabelcular pattern. Don't grow freely in space but pay attention to the trabeculae

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FL immunophenotype

CD19,20 - B cell + CD10,6,2. CD5-

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FL Ki67 levels

Low because proliferation low

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CLL/SLL male to female ratio

2:01:00

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CLL/SLL clinical

BM involvement, spleen, liver, peripheral blood, chance of immune dysregulation

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Richter's transformation

CLL/SLL transforming to diffuse large B cell lymphoma

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CLL/SLL morphology

difffuse effacement of architecture, proliferation centers in pseudofollicles. prolymphocytes paraimmunoblasts

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CLL./SLL classic morphologic feature (2)

Lymphocytosis and smudge cells

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Lymphocytosis

composed of small mature lymphocytes. Not larger than blood cells

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CLL/SLL bone marrow infiltration

generally in forms of diffuse sheets. nodular pattern means better prognosis

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CLL/SLL important markers

CD5+ and BCL2+ CD19,20+

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CLL/SLL genetics

13q = better prognosis. Others (trisomy 12, 11q dleetion, worse), 17p bad

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Zap70 indicates

positive zap70 indicates no somatic hypermutation

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Zap70 positive CLL/SLL

naive B cell, more aggressive. unmutated variable

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Zap70 negative CLL/SLL

mature B cell. indolent ones

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Most common adult leukemia

CLL/SLL

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Marginal Zone lymphoma types

3 separatate disease, extranodal, nodal, splenic

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Extranodal marginal zone lymphoma of mucosa associated lymphoid tissue

MZ lymphoma of extranodal sites

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MALT lymphoma unique association

with chronic inflammation. Also from infectious agent

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MZ lymphoma phenotype

nothign unusual. CD19,20+ CD10,6-, CD2+. Restricted light chain

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MALT lymphoma mechanism

stimulation of cell growth through NF-kappaB activation

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MALT lymphoma spread

spread from mucosal site to mucosal site. Require multiple hits to become cancerous

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MALT cytogenic hallmark

t(11:18). mostlikely fully independent

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Plasma cell morphology

clumped clockface nuclear chromatin. perinuclear clear zone, gray cytoplasm

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multiple myeloma epi

most common in african americans, second most common caucasians

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Multiple myeloma clinical

weakens bone. accumulate in areas of hematopoiesis

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Multiple myeloma morphology variants

flame cell, mott cell, plasma cell atypia

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flame cell

plasma cell with IgA and pink border

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Mott Cell

cell filled with globules of intracytoplasmic monoclonal Ig

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Bence Jones proteins

excess light chain in multiple myeloma. come out in urine. Only light chains pass through kidney

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Multiple myeloma paraprotein detection

detect with electrophoresis. Most are IgG or IgA

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Multiple myeloma paraprotein effects

immunodeficiency bc no normal IgG. Renal failure

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Cast nephropathy

Multiple myeloma caused - excess light chains in distal form tubular cast.

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Multiple myeloma renal failure mechanisms

cast nephropathy, proximal tubulopathy, hypercalcemia, amyloidosis

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proximal tubulopathy MM

the light chains are toxic to proximal tubule in which they are being reabsorbed

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hypercalcemia MM

impair renal concentration. lood volume.

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Amyloidosis MM

light chains settle as amyloid deposits. light chain settle in beta pleated sheets to form tissue deposits

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Multipe Myeloma blood smear

serum hyperviscoscity. get blood cells to line up in rouleaux

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MM paraprotein effects blood

beleding bc interfere w platelets and clotting. cryoglobulinema

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Multiple myeloma cytogenetics

13q more aggressive.

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Multiple Myeloma bone destruction

infiltration of neoplastic cells. osteoclast activation and osteoblast inhibiition. weak trabecular bone and hypercalcemia

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DLBCL presentation

rapidly enlarging single mass

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EBV DLBCL mechanism

no immune surveilance allows B cell proliferation getting genetic accidents and forming aggressive lesion

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DLBCL marcoscopy

Fish-flesh replacement. hemorrhage, necrosis, fibrosis

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DLBCL pathology

centroblastic or immunoblastic apperance. diffuse architectural effacement and large cells. often necrosis

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International Prognostic index DLBCL

a way to estimate outcomes. uses LDH etc. to measure extent of disease

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DLBCL genetic subtypes

There are germianl center types GCB and activated B cell types ABC

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GBC DLBCL outcome

generally better survival

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ABC DLBCL

worse outcome

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3 variants Burkitt Lymphoma

endemic, sporadic, immunodeficiency associated

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Endemic BL epi

2:1 males, associated with EBV.

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Sporadic BL epi

3:1 males. rare in adults

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Immunodeficient BL

association with HIV infection

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Endemic BL common site

facial bone.

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Sporadic BL common site

abdominal, ileocecal

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Immunodef BL site

lymph nodes or bone marrow

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BL morphology

Starry sky pattern. very basophilic cells. lipid vacuoles

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BL immunophenotype

germinal center B cell. CD10,6+ and BCL2-

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BL Ki67

almost 100% rapid proliferation

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Burkitt lymphoma central event

activation of cMYC

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Burkitt Lymphoma translocation

t(8:14) exrpress cMYC with IgH

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Hodgkin diagnostic cell

reed-sternberg cell

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Hodgkin cell origin

germinal center B cell=

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Hodgkin staging

stage 1 = 1 site. Stage 2 - 2 regions one side of diaphragm, stage 3 - both sides of diaphragm lymph system only, stage 4 - out of lymphatic. Type A if no symptoms

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WBC Disorders

WBC Disorders

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Radiation

Radiation

148

Radiation basic mechanism

damage DNA so that proliferating cells with damaged DNA and no check points will die

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Damage to DNA by ionization facilitated by

oxygen

150

direct ionization

directly damage DNA strand

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indirect ionization

damage DNA through reactive intermediates

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Main methods of radiation delivery

External beam radiation therapy, internal radiation therapy

153

radiosensitivity

in vitro sensitivity. Favorable cell survival curves.

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radioresponsiveness

clinical reponse of tumor during or after treatment.

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radiation therapeutic index

degree of effect on tumor compared to normal tissue

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radiation acute toxicity

skin, oral mucosa, small bowel bc rapid turnover

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radiation late toxicity

damage from cell loss and fibrosis. spine, lung, heart, brain

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4 R's radiobiology

reassortmetn of cells within cell c ycle, reoxygenation, repair of sublethal damage in normal tissue, repopulation

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concurrent chemoRT mechanism

direct enhancement of DNA damage, inhibit cellular repair, accumulate cells in radiosensitive phase, work against radioresistant cells, inhibit repopulation of tumor cells

160

RT GTV

gross tumor volume, macroscopic cancer

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RT CTV

clinical target volume

162

RT PTV

planning target volume = internal margin + setup margin

163

Bragg Peak effect

peak radiation that is applied to the actual tumor

164

Proton therapy benefit

no exit radiation. Can get higher Bragg peak effect

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Cervical Cancer screening guidelines

Pap every 3 years until 65. then every 5 years

166

CT scans for non smokers

Not recommended. CT annually for selected smokers/former smokers

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Cancer staging solid tumors

TNM, T relates to size etc of primary tumor. N relates to nodal invovlmenet. M relates to metastatic disease.

168

Effect of bone mestases

causes osteolysis or bone formation = pain

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cachexia syndrome

fatigue, weight loss, from inflammatory factors like TNF w/ cancer

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paraneoplastic syndromes

tumor produces hormones causing changes.

171

Cancer performance status

ECOG system. 4 is completely disabled

172

HPV types for cervical cancer

16 and 18

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HPV types for genital warts

6 and 11

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HPV types in anal cancer

16 and 18

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Bone marrow cellularity percent

%cellularity = 100-age

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Inherited bone marrow failure syndromes

Fanconi anemia, dyskeratosis congenita, diamond blackfan anemia

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G-CSF, GM-CSF

stimulate proliferation of myeloid progenitor cells. speeds differentiation to neutrophils

178

TPO mimetics

stimulate megakaryocyte prliferationa dn differentiation causing rise in platelet counts. includes romiplostim and eltrombopag

179

Romiplostim

peptide TOP mimetic. activate TPO receptor by binding to external domain

180

Eltrombopag

nonpeptide TOP. binds to transmembrane site on receptor and activates

181

Aged HSC differentiate preferentially into

myeloid typpe over lympho and erythro

182

pancytopenias

fanconi anemia adn dyskeratosis congenita

183

single lineage cytopenia RBC

diamond blackfan anemia

184

single lineage cytopenia myeloid

schwachman diamon syndrome, sever congenital neutropenia

185

single lineage cytopenia platelets

congenital amegakaryocytic thrombocytopenia. thrombocytopenia and absent radii, familial platelet disorder

186

Fanconi anemia presentation

congenitcal anomolies, progressive bone maorrow failure.

187

Fanconi anemia screening test

DEB/MMC hypersensitivity

188

Dyskeratosis congenita classic feautres

hyper/hypo pigmentation, leukoplakia, nail dysrotphy, bone marrow failure

189

Diamond blackfan anemia features

red cell aplasia, congenital anomolies, osteosarcoma.

190

Diamond blackfan anemia cause

defect in ribosome synthesis

191

acute leukemia presentation

abrupt pancytopenia

192

myelodysplastic syndromes

acquired persistent reduction in circulating myeloid blood cell counts, not due to nutriotion or othe illnesses

193

Myelodysplastic syndrome morphology

hypercellular marrow. megaloblastoid RBC precursors

194

t(15:17)

fuses PML transcription factor with retinoic acid receptor. in AML

195

Leukemia signs

pallor, rashes, lymph node enlargement, swollen gumjs

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Leukostasis

abnormal blood circulation, extreme circulatin gtumor burden.

197

Defining pathology AML

auer rods

198

Auer rods

aggregates of myeloperoxidase