Misc. Flashcards
How to repair double strand breaks?
HRR NHEJ
What mutation do xeroderma pigmentosum patients have?
NER, point mutation, sensitive to UV damage, get skin cancer
When does HRR occur?
Late S/G2
AT has what genetic mutation?
Impaired double strand break response- mutated ATM
Are AT patients more sensitive to ionizing RT or UV RT?
Ionizing
On MRI water is hyperintense on which?
T2
P53 causes a cell cycle arrest in what phase when there is DNA damage?
G1
Histo classification of germ cell tumor
Dysgerminoma, teratocarcinoma, teratoma
What is the chromosomal aberration with CML
9:22, BCR-ABL fusion (9:26) in dogs
What is the chromosomal aberration with Burkitt’s LSA?
8:14 tanslocation which puts myc by Ig
Syndrome in GS that is hereditary associated with a mutation in what gene?
In people BHD, in dogs RCND- FLCN (folliculin) gene produces
What tumors are involved in above syndrome? =folliculin mutation
Uterine leiomyomas, bilateral renal cystadenoma/CA, nodular dermatofibrosis (skin lesions benign)
BRCA1/2 which pathway is affected and cancer?
HRR; BRCA1- breast/ovarian, BRCA2-many cancers
HNPCC what mutation?
MMR; proteins mutated MLH1 and MSH2
How to test for proliferation?
PCNA, Ki67, AgNOR
Which growth factor is not an RTK
TGF-B- (serine/threonine), IMMUNOSUPPRESSIVE cytokine, increases fibrin, expressed in tumors
What pathway/ligand activates osteoclast?
RANK on osteoclasts, RANKL on osteoblasts
What is the JAK/STAT pathway? What are ligands?
Cytokine signaling pathway, EPO, thrombopoietin
Dogs with a HCT of >37% are __ times more likely to have a CR?
4
What % of dogs with HCT<37% remain anemic with chemo?
90%
Which K9 tumor has the highest telomerase expression?
OSA (also expressed in LSA)
What feline tumors are negative for Cox-2?
VAS, intestinal CA, pulmonary CA, LSA
What inhibits pgp?
Verapamil, Cyclosporine, tamoxifen
What is not a bifunctional alkylator?
CCNU
Name a medication that displaces methotrexate from its binding and inhibits excretion (increases tox)?
NSAIDS (aspirin)
Most predictive px factor for cutaneous SCC (both species)?
Stage
Chemo associated with Palmar-plantar erythrodysesthesia
Doxorubicin
FIV cats have an increased risk of what oral tumor?
SCC
The destruction complex in the Wnt pathway includes?
APC, axin, GSK3B
Sensitivity of U/S for detecting MCT infiltrates in the liver?
0% (43% for spleen)
Treatment with <40 Gy is associated with increased local recurrence with what oral tumor?
Acanthamatous ameloblastoma
DLT of DMFO in cats with oral SCC?
Vestibular
Which of the 4 R’s is thought to explain why SCC (oral) are radioresistant in cats?
Repopulation
Which RTK does Palladia inhibit that mastinib (and imatinib) do not?
VEGF
What was px in dogs with digit melanoma treated with murine tyrosinase vaccine?
Completion of protocol, mets at Dx, and development of mets
Most common epulis in the dog, cat?
AA, fibramatous
MC oral tumor in the cow?
Ameloblastic fibroma
What breed gets lingual HSA?
Border collies
Px in dogs with HCC?
Sx improves ST, left side are positive, elevated ALT negative
What syndromes associated with S.lupi sarcomas?
HO, spondylitis, normocytic microchromic anemia
The agreement between FNA and bx of SI tumor is?
72%, (94% for impression smears)
If an intestinal mass is SMA+, Desmin+, vimentin-, s100-, what is it?
leiomyosarcoma
Dogs with loss of wall layering are ___ times more likely to have neoplasia vs. enteritis
50.9
An intestinal tumor in the cecum of dogs is most likely a?
GIST
Which chemo agent (used in MCTs) was associated with anemia (a 10% drop in PCV)
Hydroxyurea
With multiple cutaneous MCTs what was px?
Presence of clinical signs (neg), one grade 3 (neg), one on the limb (positive), treatment with chemo (neg), mets NOT px and inicidence was 15%
RR and MC toxicity in cats with MCT?
50% and neutropenia
What hematologic changes are px with HS?
Hypoalbuminemia, thrombocytopenia, anemia
Markers for HSA?
Factor 8, cKIT, Claudin 5
Nolan’s paper for IG/IMRT urinary tumors, % of late effects?
19%
Second line chemo for TVT?
Doxorubicin
Associated with highest risk of OSCC in cats?
Flea collars (5x risk), also canned food (esp tuna) ~3.5 x risk
What increases p53 mutations in cats with OSCC?
tobacco smoke
What changes are associated with TLS in dogs? What do people get that dogs don’t?
HyperPh, hyperK, hypoCa. Don’t get increased uric acid like people
Gemcitabine did NOT have activity in what canine cancer?
LSA
Dogs vaccinated with huTyrosinase have a __ fold increase in antibodies?
2-5
What was most significant negative prognostic factor in dogs with GI LSA treated with chemo?
Diarrhea (2.3 vs. 23 months)
PARR least SN in what tissue?
Thymus, then LN/spleen, then blood.
Least SN in lymph organs b/c increased background signa
Which biomarker in K9 LSA was most useful as a negative px factor?
Plasma DNA (SAA, CRP not useful)
Which is IHC stain has poor specificity for K9 amelanotic melanoma?
S100
What is the recommended panel for amelanotic melanoma?
PNL2, Melan-A, TRP-1, and TRP-2 was created that had 100% specificity and 93.9% sensitivity in identifying canine oral amelanotic melanocytic neoplasms
Breeds associated with increased risk of ball cancer?
Boxers, GSD, shelties, afghans
Which are commonly associated with hypoglycemia as PNS?
HCC, LMS, insulinoma, also reported in LSA
What is hematologic change is associated with decreased ST in cats with VAS?
Anemia
Cats with VAS that had ____ p53 staining has decreased TTP
Cytoplasmic (no diff in ST though)
Two tumors that eat RBC’s other than HS?
OSA/HSA
IL-10 is increased in what type of mammary cancer?
Inflammatory carcinoma (dogs)
Two MC secondary CNS tumors?
HSA and pituitary
What are findings with synovial myxomas?
Dobies over-represented, 1/3 have bony lysis, 20-40% are CD18+, middle age dogs, 0% met
Which tumor type in dogs along with melanoma overexpress MAGE?
Nasal tumors
MC hematologic abnormality in mammary IC?
Coagulopathy (also a negative px factor)
MC side effects of dogs with I131 trt?
Myelosuppression
Met rate in dogs with multiple cutaneous MCTs?
15%
Cats with MM the Ig component is most commonly?
IgG
What are px factors in dogs with MM?
hyperCa, Bence jones proteinuria, bony lysis
RR of melphalan and pred in dogs with MM?
92%
MST of K9 colorectal PCTs?
15 months
Met rate/local recurrence rate of cutaneous PCTs in dogs?
2%/5%
In dogs, most common MEN is?
MEN 2a
What was associated with increased risk of intestinal cancer in cats?
Siamese, age (older), and neutered
What breeds at risk for thyroid carcinomas?
Beagle, husky, goldens (Siamese a dec’d risk)
What % of dogs on metronomics get Sterile hemorrhagic cystitis
28.5%, 216 days (only 10% in Elmslie study)
ORR of VAS to ifosfamide?
41%
What was associated with decreased ST in cats with pancreatic CA?
Effusion (30 vs. 97 days), increased ST with chemo
What tumors cause erythrocytosis as a PNS?
TVT, nasal, LMS
Metastatic disease detected in dogs with OSA via AUS? Bone scan?
0-2.5 %, 8%
Which drug is more effective for slowing dividing cells?
Bleomycin
MC mets to the adrenal gland in cats, dogs?
LSA, carcinomas
MC stage of OSA?
2b
MC genetic mutation in nasal ACA?
P53
What breed is gastric cancer hereditary?
Belgian Shepherd
An anal sac tumor 3.0 cm with lymph node mets also 3.0 cm, no distance mets. What stage?
3a
Activation of TGFB what is the essential co-smad?
4 (Smurfs inhibit)
Max fx size in pelvic RT?
3 Gy
In a new study, 116 thymomas what was px?
If sx performed, stage, and if had a second tumor, MG/ME NOT px
What also expresses TTF-1 besides thyroid tumors? (Thyroid transcription factor)
Pulmonary ACA
What stains thyroid tumors?
TTF-1, thyroglobulin and calcitonin for medullary
Bilateral thyroid tumors __times more likely to met?
16
Some px factors in adrenal tumors?
5 cm, mets, thrombus (not always), hypoK, increased BUN, nephrectomy, arrhythmias, increased sx time, histo (CA vs adenoma), pre-trt with phenoxybenzamine (+)
IHC panel for meningiomas?
Vimentin, CD34, E-cad +
Brain tumor with central mucinous part and occurs supratentorially?
Oligodendroglioma
Brain tumor in golden Ret’s and MC in the 4th ventricle?
Choroid plexus tumors
Brain tumor most likely to cause edema?
Meningioma
Most common intraxial tumor?
Astrocytoma
Besides meningiomas, also has a dural tail?
HS
Endogenous angiogenesis inhibitors?
TSP1, angiostatin/endostatin, PEX (proteolysis of MMP2)
MC site of spinal meningioma?
Cervical
What % spinal LSA are FeLV+
57% (these cats are often young, have short duration of clinical signs, and get tumors TL spine)
In the presence of O2 which HIF subunit is ubiquinated by VHL?
Alpha
Golden Rets are ___ times more likely to have concurrent heart and spleen HSA?
10.6%
MI px in cat HSA?
> 3
Cats with what tumor/treatment had increased ST with increased Ki-67?
Cutaneous SCC trt’d with RT
Antagonistic with carboplatin?
Sorefanib (in vitro)
Synergistic with carboplatin?
Gemzar (if give gemzar first?)
MC site of appendicular CSA?
Tibia > femur> humerus >radius
Bcl-2 inhibits apoptosis by directly inhibiting caspase__?
9
Dobie with tumor with lysis at the stifle?
Synovial myxoma
Prognostic factors HSA dogs?
Stage, grade, location, hemoperitoneum (renal only)
Gold standard test to assess the radiosensitivity of cells?
Clonogenic survival
The TUNEL assay evaluates what process during apoptosis?
Nuclear DNA fragmentation
The process of introducing DNA plasmids into cells is termed?
Transfection
What method is used for direct DNA sequencing?
Dideoxy-chain termination
Prognostic for TCC in dogs for metastasis?
Younger age increased nodal mets, prostate involvement increased distant mets, Higher T stage increased risk of both mets, Vasc invasion and urethral involvement with both mets
Which growth factor has serine/threonine activity?
TGF-B
Most sensitive IHC marker for melanoma?
PNL2
The role of proteins TRF1, TRF2, and RAP-1 is to?
Ensure telomere stability
Microsatellite instability is found with what deficient repair pathway?
MMR
MC histiocytic disease of the cat?
Feline progressive histiocytosis
Ames test identifies carcinogens by bacteria with independence from what aa?
Histadine
The main type of ds DNA break repair is G2 is? In G1?
HR, NHEJ
UV RT repaired by?
NER
Oxidative damage repaired by?
BER
What IHC pattern would support PNST vs. VAS in cats?
Vim+, SMA-, S100+ (VAS SMA+)
Liposomal dox in cats for VAS, MC toxicity?
Nephrotox, also got skin reactions (not PPES like dogs), and hypersensitivity
What treatment for VAS (gross dz) had best RR?
Doxil and pXRT- 70% x 7 months
Castrated male dogs have a __ x risk of prostate cancer?
3.9
What makes up the apoptosome?
Caspase 9, cytochrome C, Apaf-1
What caspases are executioners of apoptosis?
3,6,7
Invasion of dermal lymphatics by neoplastic emboli is a hallmark of what tumor?
IMC
Mammary tumor 4 cm with LN+, stage in dogs/cats?
Dog-4 (out of 5), cat-3 (out of 4)
What RTK is the largest family and allows for bidirectional transduction during vasculogenesis?
Ephrins
Most sensitive marker for tumor hypoxia?
Pimonidazole
Breed at highest risk for AGASACA?
English cocker spaniels
RR of TCC to Deramaxx?
17% (piroxicam 18%, vinbl 36%, previcox 20%)
MMP 9 is elevated in what tumor types?
Melanoma and CMT
GI tumor that is positive for cytokeratin and chromagranin A? what does it secrete? Px?
Carcinoid, serotonin, poor
An AST/ALP ratio >1 is most likely associated with?
Sarcoma or neuroendocrine (if <1 then HCC or BDC)
What markers are present/elevated in HCC but not cirrhosis?
Pgp, CD31, alpha fetal protein
What other peptide (besides insulin) is commonly secreted in canine islet cell tumors?
Pancreatic peptide
What RT dose is associated with increased survival in AA?
> 40Gy
What is the MC location for AA?
Rostral mandible
What therapy has been shown to have poor activity with feline BISC?
13-cis retinoic acid
Which tumors have increased nuclear B-catenin?
Hair follicle and melanoma
Factor associated with development of mets in VAS?
Grade
PX factors for cats with ear canal tumors?
MI, SCC, neuro signs, (grade was NOT)
Px factor for dogs with ear canal tumor?
Only extension beyond external canal
MC feline ocular tumor with worst prognosis?
Diffuse iris melanoma
Feline ocular sarcoma are more common in what sex?
Males- also have long latency, damage to lens/ch. Uveitis inc’s risk, exten beyond sclera assoc’d with poor px
Negative px factors in K9 pituitary tumors?
Pit to brain height, pit to brain area, lack of trt, endocrine inactive
Breed at highest risk of boob cancer and gets BRCA mutations?
English Springer spaniel
MST of muzzle MCT w/o mets?
52 months (14 with mets< 30 overall)
What NOT expressed in differentiated plasma cells?
Pax5
What was outcome of dogs vaccine with CD40L in B cell LSA?
Improved second remission rate
When serum ferritin is > 7200, it is predictive of HS if you rule out what disease?
IMHA
What spinal tumors occur in the T/L spine and are WT-1+?
Nephroblastoma
What tumor is CD34+, Vimentin + and E-cad +?
Meningioma
Which pathway would you need to block to inhibit ezrin?
Ron
Which (drug?) inhibits RANK by acting as a soluble decoy?
Osteoprotegin
Px factors in cats with nasal LSA?
Anemia, cribriform lysis, >32Gy
Which pathway leads to Increased MMP in dogs with OSA?
STAT3
Which cats are likely to benefit from chemo with mammary tumors?
Stage 3 and radical mastectomy
What does STAT do in the cell?
Anti-apoptotic, proliferation, angiogenesis
What are the hallmarks of cancer?
Sustaining proliferative signaling evading growth suppressors resisting cell death enabling replicative immortality inducing angiogenesis activating invasion/metastasis reprogramming of energy metabolism evading immune destruction
What are the three steps in carcinogenesis?
Initiation, protomotion, progression
Increased MGMT causes resistance to what class of chemo dugs?
Alkylators
Name DNA virus?
SV40, adenovirus, polymxyovirus, papillomavirus
What location regresses quicker with papilloma and were do cats get it?
Mouth faster than skin, DSH get skin
Which subgroup of FeLV is transmitted and is in vaccine?
A
Name core protein detected by IFA and ELISA for FeLV?
P27
What test rules out FeSV?
FeLV- if negative not infected. FeSV is an acutely transforming virus that needs FeLV to replicate
Which virus vaccine cross reacts with snap test?
FIV
What are integrins?
Connect cell to ECM, activate FAK/Src, Ras, ERK, Rho
How is RAS usually mutated?
Point mutation
What pathways are active by RAS?
Raf, Ral, PI3K
What diseases are Wnt pathway mutated?
FAP and colon cancer (also hair follicle tumors and melanoma?)
How does LOH happen?
Mitotic recombination, chromosomal non-disjunction, gene conversion
Gatekeeper genes?
Rb, p53, PTEN, BRCA1/2 (directly antiproliferative or proapoptotic)
Caretaker genes?
ATM, XP, MSH2/MLH1 (help with genomic integrity)
How can p53 act like an oncogene?
Point mutation cause dominant negative effect
How does p53 cause cell cycle arrest?
P53 activates p21 and stops G1/S checkpoint
How does p53 cause apoptosis?
Activates PUMA, NOX, Bak/bim
What are two apoptosis pathways?
Death receptor and mitochondrial
What connects the two apoptosis pathways?
Caspase 8
Is E-cad high or low in aggressive tumors?
Low expression bc lose connection btw cells so can detach from primary
What pathways does VEGF stimulate?
PI3K, BcL2
Which VEGFR is associated with lymphatics?
VEGFR3 (binds VEGF B and C)
What are endogenous pro angiogenic signals?
VEGF, PIGF, PDGF, TNFa, TGFb, Ang1,2 IL8
What treatments are antiangiogenic?
Bevacizumab, metronomic, thalidomide, angiostatin
What pathways synthesize Hif?
PI3K, mTOR
What drugs are MDRI substrates?
Anthracyclins, vincas, MTX, Epipodophyllotoxins, taxanes, topotecan
What 2 drugs can reverse pgp resistance?
Verapamil and cyclosporine A
What drug classes does glutathione inactivate?
Doxorubicin, alkylators, platinums
What cells express MHC I and MHC II?
All cells I, only APCs II, MHC III is involved in complement
What energy pathway do most cancer cells use?
aerobic glycolysis, cancer cells need more gluc/ATP and produce high lactate
What are markers for Tregs?
CD4, CD25, FoxP3
What do Treg secrete?
TGFb, IL-10
What is the primary immunosurveillance molecule?
IFN-gamma, levels should change with immune response
Intrinsic markers of hypoxia?
Hif-a, GLUT-1, CAIX
Radiation induced fibrosis due to what factor?
TGFB
As you increase the amount of time to give total dose of RT, you increase which R?
Repopulation
Which R results in a substantial increase in tumor sensitivity during fractionated treatment?
Reoxygenation
What is the critical parameter regarding normal tissue reponse to radiation therapy?
Fraction size
The L-Q model does not take into account which treatment parameter?
Treatment time
What drug has been linked to a cause of pseudolymphoma in a cat?
Phenobarbital (reversed by switching to Keppra)
Which is not an aminobisphosphonate?
Clodronate
Which is the most potent bisphosphonate?
Zoledronate
Which are prodrugs?
Procarbazine, Ifosfamide, Cytoxan, DTIC, dexrazoxane
In addition to doxorubicin, this drug forms reactive oxygen species?
Bleomycin
DNA vaccine in dogs against TERT did what?
Prolonged ST and time to first relapse and overcame tolerance in >90%
2 prognostic factors associated with increased risk of late toxicities for pelvic RT?
Large trt field and perianal tumor
P27 is highest/lowest in which phases of the cell cycle?
Go/late G1
Inhibition of what pathway leads to autophagy?
mTOR
Which pathway leads to inactivation of Rb via induction of cyclin D?
Ras
What transcription factors are involved in EMT?
Snail, slug, twist, LEF
Small molecule inhibitors for EGFR?
Cetuximab, Erlotinib, Gefitinib, Panitumumab
What inhibits IAP (inhibitors of apoptosis)?
Smac/Diablo
The death receptor and mitochondrial pathways are lined by which caspase?
Caspase 8
Four ways to test for apoptosis?
Alterations in membrane fxn (Annexin V)
release of cytochrome C (IHC, or WB)
activation of caspases (WB)
fragmentation of nuclear DNA (TUNEL)
This receptor pathway lacks intrinsic tyrosine kinase activity?
Cytokine R’s (use Jaks)
Which hormone suppresses Cox?
Estrogen
This pathway involves a series of cleavage events to be activated?
Notch
What is cross presentation?
When extracelluar antigens are presented by MHC I
Major toxicity with IL-2?
Capillary leak syndrome
Major toxicity with TNF-a?
Septic shock syndrome
Method of choice for detecting LOH?
FISH
In addition to dendritic cells, what other immune cell expresses CD40?
B cells, (CD40L on Tcells)
LFA-1 is expressed on___ and binds to ____?
Lymphocytes and binds to ICAM-1 on dendritic cells
Highest levels of pgp in what two tissues?
Kidney and adrenal gland
Bortezomib inhibits?
Proteosome
Tipifranib is a farnesyltransferase inhibitor which results in blockade of what pathway?
Ras
