Test Review Flashcards
Hoe does snail relate to cmt
Snail expression correlated signif w Grade Histo type Lymph invasion snail, hallmark of emt, may play nb role in invasion and mets of cmt
Are erbB1 and 2 expressed in CMT? Significance?
Erbb1 over expression in30% w 91% homology
Erbb2 over expression in 40% w 92% homology
Cetuximab and traztuzumab significantly inhibit tumor cell proliferation dot this
Feline Lung carc markers
Ttf1
Surfactant protein a
Egfr mutant
P53 positive
No Kras or p53 mutants
Feline lgl lsa
SI IEL origin for feline LGL 90% T cell CD103 circ IELs CD8aa expressed by IELs in cats None lived over 2.8m jejunum mc Nphilia mc leukogram change
Canine LGL CLL is CD11d+ splenic pulp origin
Prognostic variables feline LSA
For survival:
BM involvement, stage, substance, use of rt (most nasal)
MV analysis:
Only second remission protocol (mopp better)
PGP NOT predictive of survival
LSA v iBD in gi biopsy samples
Important differences: lymph infiltrate beyond mucosa, heterogeneity, epitheliotropism, nuclear size of lymphs
100% specific for LSA: intravasc infiltrate, mets, serosal infiltrate
63% T cell v 13% B cell
Bcl-2 in IBD v LSA
Significantly higher cells were + in LSA v iBD (90% v 60%)
May be useful as thp target
Ccnu for cut LSA
Orr 78-83% x 3-3.5m
Cr 17-33%
Resp dur for cr not reached
72% ln involvement
Sign diff in ttp in cum ccnu dose and # cycles but resp and non resp
Dacarbazine single agent for relapsed LSA
Orr 35%
Pfi 43 d (1.4m)
Tpenia
Effect of pred on lymph marker expression
Decreased proportions of:
CD3, CD4. CD 21. CD 45RA. CD90
CD3 most
Decreased intensity of:
CD18. CD45.
Culture w pred caused sign drop in all markers and DNA fragmentation
Plasma DNA
Higher in dogs w LSA and leukemia
If over 24 ng ml = shorter remission
Ccnu and pred first line for LSA
Orr 53% x 1.3m (worse than rescue 2.9m)
MST 3.7m
MV- FEmales, higher total ccnu = longer dfi
Pred could have done this!
T cell markers
Cd 4, 8, 3, 5, 45
B cell LSA markers
CD 20, 21, 45, 79, pax5, igM, IgG
Cat liver tumors
Primary > metastatic Benign > malignant Cholangiocarcinoma #1 primary malig Bile duct adenomas common #1 tumor Hypoglycemia dt hep adenomas Azotemia from liver tumors
Ccnu for hs
Orr 46%
Mst 3.5m
Mst responders 5.7m
Dog spontaneous hemoperitoneum
80% of bleeding solitary and mfo = malignant
All solitary malignant = HSA
71% MFO malignant = HSA
HSA tumor vaccine
LDC (cationic liposome and DNA complexes) was adjuvant for allogeneic tumor vax of lysates of canine HSA cell lines
Stage 2 HSA (splenic) given vax + doxorubicin had significantly longer MST but no change in DFI
Strong humoral IR against LDC
Most mounted aby response against canine HSA cells
Mds dx
Mds eb = blasts in marrow >5% <1 poor px
Mm px factors dog and cat
Dog - hypercal, bence jones, extensive bony lysis
Cat- hypercal, bence jones, bone Lz w path fx, anemia, azotemia, High creat, high prot after 8w treatment (all indicate aggressive form MST 5d v 12.9m)
Primary v secondary polycythemia
Indolent but gradual myelofibrosis
Primary:
High RBC mass (2 to tissue hypoxia causing appropriate high epo production), EPO low to low normal
Secondary: plasma volume is decreased (hypovolemia, dehydration, RBC not increased), EPO high
Common feline mm findings
Atypical plasma cell morph 83% Decreased cholesterol 69% Bone lesions 50% Non cutaneous extramedullary/multiorgan involvement 1Oo% Anemia 69%
Trends in feline gi neoplasia
#1 LSA. 80% LSA in SI #1 non lymphoid is ADCA ADCA is #1 LI tumor. 69% of ADCA is LI
Ins risk: Siamese ESP ADCA. Age after 7
Dec risk: intact
Testicular tumors
Setoli a bit less common and younger
Sheltie/Collie 5x more likely than other breeds!
They get sertoli or mixed sertoli/seminoma
Norwegian elkhounds 100% seminomas
Decreased risk: lab, gsp, flat coat, rottie
Px factors canine insulinoma
Tumor size…dfi
Ki67…dfi and os
Indicators of malig in adrenocort tumors
Adrenal carc
Over 2 cm, invasive, ki67 > 2.4%
Peripheral fibrosis, capsular invasion, trabecular growth pattern, hemorrhage, necrosis, single cell necrosis
Adenomas
Hempoiesis, fibrin thrombi, cytopl vacuoles
Adrenal markers…pheo v ADCA
Pheo chromogranin a, synaptophysin
ADCA, melan a, ki67
Dog digit tumor mets
SCC 3-9%. Later up to 23%
Melanoma 10-40%. Later up to 40%
OSA 24%
Mets at dx don’t change ST
Secondary brain dog
MC than primary HSA 1, pituitary 2, LSA 3, carcinoma 4 Cerebrum Me ration change Necropsy, same tumor in lung 47%, kidney 35%, heart 31%
Spinal dog and cat
Dog - mening 1 HSA 2
Cat - LSA 1 OSA 2
Boxer cervical mening
Goldens gsd TL nephroblastoma
Cat chemo tox
Cisplat pulm edema Hu methHb Doxorubicin kidney insuff Ccnu lung fibrosis (chronic) Vbl overdose SIADH Phenobarbital pseudoLSA
Chemo in preg
3stages of fetal devel:
Early embryogenesis (embryonic death)
Organogenesis (death or major malf)
Fetal growth ( fxn rather than struct def)
Relatively safe after organogenesis
D/c 2-3 weeks before deliv to avoid fetal myelosuppression
Moa misoprostol
Prostaglandin analog for tx or preventing gastric ulcers
Direct action on parietal cells
Inhibits gastric acid secretion
Metronomic chlorambucil
ORR 11%
CB 62%
Median PFI 2m. MST 5.1m
Response significantly assoc w PFI (not survival)
Some CRs did great, MCT 15.6m, TC >2.2y, STS in remission >8m
Palladia targets
VEGFR pDGFR CSF1R FLT3 RET
CCNU denamarin
ALT increase: 68% v 84%
Liver tox: 4% v 28%
Idarubicin
PO MTD 22 mg m2 AE npenia tpenia 68% 58% responded (29% prev had ardria) Well tolerated
In people, less heart tox, less mdr effluent, better bbb penetration
Abcb1 breeds
Collie 77 Long haired whippet 58 Aus shep 47 Mini Aussie 37 Silken wind hound 31 Sheltie 12 Mix 11 GSD 10 OES 2.5 Border collie 1
Hematologic tox of which drugs depend on auc
Doxorubicin
Carboplatin
5fu
Cladribine
VAS express what
PDGF and PDGFR EGF and EGFR FGFb TGFa and TGFb cKit
Which factors have role in bone resorp
PTHrP IL1 TNFa RANKL OPG TGFB1
What do rankl, opg, and TGFb do
RANKL stimulates OC activation, normally expressed by OB, also some tumors. Increases bone resorption
OPG is soluble decoy receptor for RANKL, inhibits OC activation
TGFb stimulates and inhibits effects on OC bone resorption
PTHrP, IL1, TNF stimulate OB expression of RANKL and Tf OC bone resorption
Masitinib targets
Kit
PDGFR a/b
LIN
FGFR3
Imatinib targets
Kit
PDGFR
Bcr-abl
Investigate mass at vax site if
Mass is at least 2 cm
Evident 3m post vax
Increasing in size more than 4 weeks post vax
WHO primary Lung tumor staging
T1 solitary tumor
T2 mult tumors any size
T3 tumor invading neighboring tissue
N LN involve
M mets
Pall RT in 5 cats w OMM
ORR
msT
ORR 60%
MST 4.9m
Dogs w OMM tx with XRT
ORR 82%. CR 51%.
RF: location (rostral v cd), bone lysis, tumor vol (macro v micro)
O RF MST 21m, 1 RF 11m, 2 RF 5m, 3 RF 3m
Tumor vol + location = lung mets, MST, recur
Bone lysis = recur, MST
Melanoma cocktail
Melan A, PLN2, TRP 1, TRP 2
94% sens 100% spec
Myoepithelial markers in mammary
p63
CK14
Calponin
Cmt behavior
74% malig
58% new tumor in ipsilat gland
77% of dogs w malig tumor got 2nd malig
3% got tumor in contralat gland
Unilateral rad mastect may be warranted
Ddavp and cmt
Improves MST and DFI
Breeds cut HSA
Whippet pit bull Dalmatian beagle Italian grey hound
Dermal HSA tx w only surgery
77% recur at median 7m (even clean margins!)
Increased local recurrence: predisposed breed, ventrum, mult masses (NOT INC MARGINS)
Increased risk mets - sq invasion
Decreased risk mets - predisposed breeds
Increased survival
Predisposed breeds lived longer
Ventral location and solar induced lived longer
Mets and hemoabdomen lived shorter
MST 2.7y
34% mets at med 11 m
Ihc type a v b synoviocytes
Type A: phagocytic macrophages, CD18+
Type B: mesenchymal, produce synovium
Vimentin+, cadherin+, HSP25+
What canine cells are sensitive to Sorafenib
What chemo drug did it antagonize
OSA
Carbo
Sorafenib (nexavar) targets
Vegfr 2/3 PDGFR b Flt3 CKit B raf C raf
Inflammatory mammary carcinoma
Prognostic
IHC
Presence of coagulopathy
Medical tx
MST 2m
Positive: CK, CK 14, vimentin, vWF
Neg: actin, desmin, CD31, CD34
Recur of inc excised STS
Grade and MI are sign assoc w tumor recur for marginally excised tumors. Grade stronger.
Overall recur 23%. TTR 12m.
Grade 1, 7% recurred
Grade 2, 34% recurred
Grade 3, 75% recurred
PCNA
Subunit of DNA polymerase delta
Involved in DNA repair
Max expression in s phase
Ki67
Nuclear protein expressed in all but G0
Determines # cells actively involved in cell cycle
Agnor
Nucleolar structures involved in ribosomal RNA transcription
Correlated w RAte of proliferation
Increased agnor and ki67 tell us what
Increased MCT recurrence
Increased mets
Increased MCT related death
If only ki67 >23 cells/grid – all three
If only agnor > 54 cells – inc tumor rec + death
Grade 3 MCT w chemo
What was px
Tumor size (>3cm bad)
LN status assoc w PFS
Only LN status assoc w MST
PFI 3.3 v 11.6 m (w wo LN)
MST 6.5 v 16.8 m (LN mets)
