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Misc. Flashcards

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1
Q

How to repair double strand breaks?

A

HRR NHEJ

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2
Q

What mutation do xeroderma pigmentosum patients have?

A

NER, point mutation, sensitive to UV damage, get skin cancer

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3
Q

When does HRR occur?

A

Late S/G2

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4
Q

AT has what genetic mutation?

A

Impaired double strand break response- mutated ATM

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5
Q

Are AT patients more sensitive to ionizing RT or UV RT?

A

Ionizing

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6
Q

On MRI water is hyperintense on which?

A

T2

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7
Q

P53 causes a cell cycle arrest in what phase when there is DNA damage?

A

G1

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8
Q

Histo classification of germ cell tumor

A

Dysgerminoma, teratocarcinoma, teratoma

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9
Q

What is the chromosomal aberration with CML

A

9:22, BCR-ABL fusion (9:26) in dogs

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10
Q

What is the chromosomal aberration with Burkitt’s LSA?

A

8:14 tanslocation which puts myc by Ig

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11
Q

Syndrome in GS that is hereditary associated with a mutation in what gene?

A

In people BHD, in dogs RCND- FLCN (folliculin) gene produces

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12
Q

What tumors are involved in above syndrome? =folliculin mutation

A

Uterine leiomyomas, bilateral renal cystadenoma/CA, nodular dermatofibrosis (skin lesions benign)

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13
Q

BRCA1/2 which pathway is affected and cancer?

A

HRR; BRCA1- breast/ovarian, BRCA2-many cancers

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14
Q

HNPCC what mutation?

A

MMR; proteins mutated MLH1 and MSH2

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15
Q

How to test for proliferation?

A

PCNA, Ki67, AgNOR

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16
Q

Which growth factor is not an RTK

A

TGF-B- (serine/threonine), IMMUNOSUPPRESSIVE cytokine, increases fibrin, expressed in tumors

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17
Q

What pathway/ligand activates osteoclast?

A

RANK on osteoclasts, RANKL on osteoblasts

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18
Q

What is the JAK/STAT pathway? What are ligands?

A

Cytokine signaling pathway, EPO, thrombopoietin

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19
Q

Dogs with a HCT of >37% are __ times more likely to have a CR?

A

4

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20
Q

What % of dogs with HCT<37% remain anemic with chemo?

A

90%

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21
Q

Which K9 tumor has the highest telomerase expression?

A

OSA (also expressed in LSA)

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22
Q

What feline tumors are negative for Cox-2?

A

VAS, intestinal CA, pulmonary CA, LSA

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23
Q

What inhibits pgp?

A

Verapamil, Cyclosporine, tamoxifen

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24
Q

What is not a bifunctional alkylator?

A

CCNU

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25
Q

Name a medication that displaces methotrexate from its binding and inhibits excretion (increases tox)?

A

NSAIDS (aspirin)

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26
Q

Most predictive px factor for cutaneous SCC (both species)?

A

Stage

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27
Q

Chemo associated with Palmar-plantar erythrodysesthesia

A

Doxorubicin

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28
Q

FIV cats have an increased risk of what oral tumor?

A

SCC

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29
Q

The destruction complex in the Wnt pathway includes?

A

APC, axin, GSK3B

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30
Q

Sensitivity of U/S for detecting MCT infiltrates in the liver?

A

0% (43% for spleen)

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31
Q

Treatment with <40 Gy is associated with increased local recurrence with what oral tumor?

A

Acanthamatous ameloblastoma

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32
Q

DLT of DMFO in cats with oral SCC?

A

Vestibular

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33
Q

Which of the 4 R’s is thought to explain why SCC (oral) are radioresistant in cats?

A

Repopulation

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34
Q

Which RTK does Palladia inhibit that mastinib (and imatinib) do not?

A

VEGF

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35
Q

What was px in dogs with digit melanoma treated with murine tyrosinase vaccine?

A

Completion of protocol, mets at Dx, and development of mets

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36
Q

Most common epulis in the dog, cat?

A

AA, fibramatous

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37
Q

MC oral tumor in the cow?

A

Ameloblastic fibroma

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38
Q

What breed gets lingual HSA?

A

Border collies

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39
Q

Px in dogs with HCC?

A

Sx improves ST, left side are positive, elevated ALT negative

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40
Q

What syndromes associated with S.lupi sarcomas?

A

HO, spondylitis, normocytic microchromic anemia

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41
Q

The agreement between FNA and bx of SI tumor is?

A

72%, (94% for impression smears)

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42
Q

If an intestinal mass is SMA+, Desmin+, vimentin-, s100-, what is it?

A

leiomyosarcoma

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43
Q

Dogs with loss of wall layering are ___ times more likely to have neoplasia vs. enteritis

A

50.9

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44
Q

An intestinal tumor in the cecum of dogs is most likely a?

A

GIST

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45
Q

Which chemo agent (used in MCTs) was associated with anemia (a 10% drop in PCV)

A

Hydroxyurea

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46
Q

With multiple cutaneous MCTs what was px?

A

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%

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47
Q

RR and MC toxicity in cats with MCT?

A

50% and neutropenia

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48
Q

What hematologic changes are px with HS?

A

Hypoalbuminemia, thrombocytopenia, anemia

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49
Q

Markers for HSA?

A

Factor 8, cKIT, Claudin 5

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50
Q

Nolan’s paper for IG/IMRT urinary tumors, % of late effects?

A

19%

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51
Q

Second line chemo for TVT?

A

Doxorubicin

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52
Q

Associated with highest risk of OSCC in cats?

A

Flea collars (5x risk), also canned food (esp tuna) ~3.5 x risk

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53
Q

What increases p53 mutations in cats with OSCC?

A

tobacco smoke

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54
Q

What changes are associated with TLS in dogs? What do people get that dogs don’t?

A

HyperPh, hyperK, hypoCa. Don’t get increased uric acid like people

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55
Q

Gemcitabine did NOT have activity in what canine cancer?

A

LSA

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56
Q

Dogs vaccinated with huTyrosinase have a __ fold increase in antibodies?

A

2-5

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57
Q

What was most significant negative prognostic factor in dogs with GI LSA treated with chemo?

A

Diarrhea (2.3 vs. 23 months)

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58
Q

PARR least SN in what tissue?

A

Thymus, then LN/spleen, then blood.

Least SN in lymph organs b/c increased background signa

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59
Q

Which biomarker in K9 LSA was most useful as a negative px factor?

A

Plasma DNA (SAA, CRP not useful)

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60
Q

Which is IHC stain has poor specificity for K9 amelanotic melanoma?

A

S100

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61
Q

What is the recommended panel for amelanotic melanoma?

A

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

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62
Q

Breeds associated with increased risk of ball cancer?

A

Boxers, GSD, shelties, afghans

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63
Q

Which are commonly associated with hypoglycemia as PNS?

A

HCC, LMS, insulinoma, also reported in LSA

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64
Q

What is hematologic change is associated with decreased ST in cats with VAS?

A

Anemia

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65
Q

Cats with VAS that had ____ p53 staining has decreased TTP

A

Cytoplasmic (no diff in ST though)

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66
Q

Two tumors that eat RBC’s other than HS?

A

OSA/HSA

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67
Q

IL-10 is increased in what type of mammary cancer?

A

Inflammatory carcinoma (dogs)

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68
Q

Two MC secondary CNS tumors?

A

HSA and pituitary

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69
Q

What are findings with synovial myxomas?

A

Dobies over-represented, 1/3 have bony lysis, 20-40% are CD18+, middle age dogs, 0% met

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70
Q

Which tumor type in dogs along with melanoma overexpress MAGE?

A

Nasal tumors

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71
Q

MC hematologic abnormality in mammary IC?

A

Coagulopathy (also a negative px factor)

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72
Q

MC side effects of dogs with I131 trt?

A

Myelosuppression

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73
Q

Met rate in dogs with multiple cutaneous MCTs?

A

15%

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74
Q

Cats with MM the Ig component is most commonly?

A

IgG

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75
Q

What are px factors in dogs with MM?

A

hyperCa, Bence jones proteinuria, bony lysis

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76
Q

RR of melphalan and pred in dogs with MM?

A

92%

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77
Q

MST of K9 colorectal PCTs?

A

15 months

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78
Q

Met rate/local recurrence rate of cutaneous PCTs in dogs?

A

2%/5%

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79
Q

In dogs, most common MEN is?

A

MEN 2a

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80
Q

What was associated with increased risk of intestinal cancer in cats?

A

Siamese, age (older), and neutered

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81
Q

What breeds at risk for thyroid carcinomas?

A

Beagle, husky, goldens (Siamese a dec’d risk)

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82
Q

What % of dogs on metronomics get Sterile hemorrhagic cystitis

A

28.5%, 216 days (only 10% in Elmslie study)

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83
Q

ORR of VAS to ifosfamide?

A

41%

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84
Q

What was associated with decreased ST in cats with pancreatic CA?

A

Effusion (30 vs. 97 days), increased ST with chemo

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85
Q

What tumors cause erythrocytosis as a PNS?

A

TVT, nasal, LMS

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86
Q

Metastatic disease detected in dogs with OSA via AUS? Bone scan?

A

0-2.5 %, 8%

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87
Q

Which drug is more effective for slowing dividing cells?

A

Bleomycin

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88
Q

MC mets to the adrenal gland in cats, dogs?

A

LSA, carcinomas

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89
Q

MC stage of OSA?

A

2b

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90
Q

MC genetic mutation in nasal ACA?

A

P53

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91
Q

What breed is gastric cancer hereditary?

A

Belgian Shepherd

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92
Q

An anal sac tumor 3.0 cm with lymph node mets also 3.0 cm, no distance mets. What stage?

A

3a

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93
Q

Activation of TGFB what is the essential co-smad?

A

4 (Smurfs inhibit)

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94
Q

Max fx size in pelvic RT?

A

3 Gy

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95
Q

In a new study, 116 thymomas what was px?

A

If sx performed, stage, and if had a second tumor, MG/ME NOT px

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96
Q

What also expresses TTF-1 besides thyroid tumors? (Thyroid transcription factor)

A

Pulmonary ACA

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97
Q

What stains thyroid tumors?

A

TTF-1, thyroglobulin and calcitonin for medullary

98
Q

Bilateral thyroid tumors __times more likely to met?

A

16

99
Q

Some px factors in adrenal tumors?

A

5 cm, mets, thrombus (not always), hypoK, increased BUN, nephrectomy, arrhythmias, increased sx time, histo (CA vs adenoma), pre-trt with phenoxybenzamine (+)

100
Q

IHC panel for meningiomas?

A

Vimentin, CD34, E-cad +

101
Q

Brain tumor with central mucinous part and occurs supratentorially?

A

Oligodendroglioma

102
Q

Brain tumor in golden Ret’s and MC in the 4th ventricle?

A

Choroid plexus tumors

103
Q

Brain tumor most likely to cause edema?

A

Meningioma

104
Q

Most common intraxial tumor?

A

Astrocytoma

105
Q

Besides meningiomas, also has a dural tail?

A

HS

106
Q

Endogenous angiogenesis inhibitors?

A

TSP1, angiostatin/endostatin, PEX (proteolysis of MMP2)

107
Q

MC site of spinal meningioma?

A

Cervical

108
Q

What % spinal LSA are FeLV+

A

57% (these cats are often young, have short duration of clinical signs, and get tumors TL spine)

109
Q

In the presence of O2 which HIF subunit is ubiquinated by VHL?

A

Alpha

110
Q

Golden Rets are ___ times more likely to have concurrent heart and spleen HSA?

A

10.6%

111
Q

MI px in cat HSA?

A

> 3

112
Q

Cats with what tumor/treatment had increased ST with increased Ki-67?

A

Cutaneous SCC trt’d with RT

113
Q

Antagonistic with carboplatin?

A

Sorefanib (in vitro)

114
Q

Synergistic with carboplatin?

A

Gemzar (if give gemzar first?)

115
Q

MC site of appendicular CSA?

A

Tibia > femur> humerus >radius

116
Q

Bcl-2 inhibits apoptosis by directly inhibiting caspase__?

A

9

117
Q

Dobie with tumor with lysis at the stifle?

A

Synovial myxoma

118
Q

Prognostic factors HSA dogs?

A

Stage, grade, location, hemoperitoneum (renal only)

119
Q

Gold standard test to assess the radiosensitivity of cells?

A

Clonogenic survival

120
Q

The TUNEL assay evaluates what process during apoptosis?

A

Nuclear DNA fragmentation

121
Q

The process of introducing DNA plasmids into cells is termed?

A

Transfection

122
Q

What method is used for direct DNA sequencing?

A

Dideoxy-chain termination

123
Q

Prognostic for TCC in dogs for metastasis?

A

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

124
Q

Which growth factor has serine/threonine activity?

A

TGF-B

125
Q

Most sensitive IHC marker for melanoma?

A

PNL2

126
Q

The role of proteins TRF1, TRF2, and RAP-1 is to?

A

Ensure telomere stability

127
Q

Microsatellite instability is found with what deficient repair pathway?

A

MMR

128
Q

MC histiocytic disease of the cat?

A

Feline progressive histiocytosis

129
Q

Ames test identifies carcinogens by bacteria with independence from what aa?

A

Histadine

130
Q

The main type of ds DNA break repair is G2 is? In G1?

A

HR, NHEJ

131
Q

UV RT repaired by?

A

NER

132
Q

Oxidative damage repaired by?

A

BER

133
Q

What IHC pattern would support PNST vs. VAS in cats?

A

Vim+, SMA-, S100+ (VAS SMA+)

134
Q

Liposomal dox in cats for VAS, MC toxicity?

A

Nephrotox, also got skin reactions (not PPES like dogs), and hypersensitivity

135
Q

What treatment for VAS (gross dz) had best RR?

A

Doxil and pXRT- 70% x 7 months

136
Q

Castrated male dogs have a __ x risk of prostate cancer?

A

3.9

137
Q

What makes up the apoptosome?

A

Caspase 9, cytochrome C, Apaf-1

138
Q

What caspases are executioners of apoptosis?

A

3,6,7

139
Q

Invasion of dermal lymphatics by neoplastic emboli is a hallmark of what tumor?

A

IMC

140
Q

Mammary tumor 4 cm with LN+, stage in dogs/cats?

A

Dog-4 (out of 5), cat-3 (out of 4)

141
Q

What RTK is the largest family and allows for bidirectional transduction during vasculogenesis?

A

Ephrins

142
Q

Most sensitive marker for tumor hypoxia?

A

Pimonidazole

143
Q

Breed at highest risk for AGASACA?

A

English cocker spaniels

144
Q

RR of TCC to Deramaxx?

A

17% (piroxicam 18%, vinbl 36%, previcox 20%)

145
Q

MMP 9 is elevated in what tumor types?

A

Melanoma and CMT

146
Q

GI tumor that is positive for cytokeratin and chromagranin A? what does it secrete? Px?

A

Carcinoid, serotonin, poor

147
Q

An AST/ALP ratio >1 is most likely associated with?

A

Sarcoma or neuroendocrine (if <1 then HCC or BDC)

148
Q

What markers are present/elevated in HCC but not cirrhosis?

A

Pgp, CD31, alpha fetal protein

149
Q

What other peptide (besides insulin) is commonly secreted in canine islet cell tumors?

A

Pancreatic peptide

150
Q

What RT dose is associated with increased survival in AA?

A

> 40Gy

151
Q

What is the MC location for AA?

A

Rostral mandible

152
Q

What therapy has been shown to have poor activity with feline BISC?

A

13-cis retinoic acid

153
Q

Which tumors have increased nuclear B-catenin?

A

Hair follicle and melanoma

154
Q

Factor associated with development of mets in VAS?

A

Grade

155
Q

PX factors for cats with ear canal tumors?

A

MI, SCC, neuro signs, (grade was NOT)

156
Q

Px factor for dogs with ear canal tumor?

A

Only extension beyond external canal

157
Q

MC feline ocular tumor with worst prognosis?

A

Diffuse iris melanoma

158
Q

Feline ocular sarcoma are more common in what sex?

A

Males- also have long latency, damage to lens/ch. Uveitis inc’s risk, exten beyond sclera assoc’d with poor px

159
Q

Negative px factors in K9 pituitary tumors?

A

Pit to brain height, pit to brain area, lack of trt, endocrine inactive

160
Q

Breed at highest risk of boob cancer and gets BRCA mutations?

A

English Springer spaniel

161
Q

MST of muzzle MCT w/o mets?

A

52 months (14 with mets< 30 overall)

162
Q

What NOT expressed in differentiated plasma cells?

A

Pax5

163
Q

What was outcome of dogs vaccine with CD40L in B cell LSA?

A

Improved second remission rate

164
Q

When serum ferritin is > 7200, it is predictive of HS if you rule out what disease?

A

IMHA

165
Q

What spinal tumors occur in the T/L spine and are WT-1+?

A

Nephroblastoma

166
Q

What tumor is CD34+, Vimentin + and E-cad +?

A

Meningioma

167
Q

Which pathway would you need to block to inhibit ezrin?

A

Ron

168
Q

Which (drug?) inhibits RANK by acting as a soluble decoy?

A

Osteoprotegin

169
Q

Px factors in cats with nasal LSA?

A

Anemia, cribriform lysis, >32Gy

170
Q

Which pathway leads to Increased MMP in dogs with OSA?

A

STAT3

171
Q

Which cats are likely to benefit from chemo with mammary tumors?

A

Stage 3 and radical mastectomy

172
Q

What does STAT do in the cell?

A

Anti-apoptotic, proliferation, angiogenesis

173
Q

What are the hallmarks of cancer?

A 
Sustaining proliferative signaling
evading growth suppressors
resisting cell death
enabling replicative immortality
inducing angiogenesis
activating invasion/metastasis 
reprogramming of energy metabolism
evading immune destruction
174
Q

What are the three steps in carcinogenesis?

A

Initiation, protomotion, progression

175
Q

Increased MGMT causes resistance to what class of chemo dugs?

A

Alkylators

176
Q

Name DNA virus?

A

SV40, adenovirus, polymxyovirus, papillomavirus

177
Q

What location regresses quicker with papilloma and were do cats get it?

A

Mouth faster than skin, DSH get skin

178
Q

Which subgroup of FeLV is transmitted and is in vaccine?

A

A

179
Q

Name core protein detected by IFA and ELISA for FeLV?

A

P27

180
Q

What test rules out FeSV?

A

FeLV- if negative not infected. FeSV is an acutely transforming virus that needs FeLV to replicate

181
Q

Which virus vaccine cross reacts with snap test?

A

FIV

182
Q

What are integrins?

A

Connect cell to ECM, activate FAK/Src, Ras, ERK, Rho

183
Q

How is RAS usually mutated?

A

Point mutation

184
Q

What pathways are active by RAS?

A

Raf, Ral, PI3K

185
Q

What diseases are Wnt pathway mutated?

A

FAP and colon cancer (also hair follicle tumors and melanoma?)

186
Q

How does LOH happen?

A

Mitotic recombination, chromosomal non-disjunction, gene conversion

187
Q

Gatekeeper genes?

A

Rb, p53, PTEN, BRCA1/2 (directly antiproliferative or proapoptotic)

188
Q

Caretaker genes?

A

ATM, XP, MSH2/MLH1 (help with genomic integrity)

189
Q

How can p53 act like an oncogene?

A

Point mutation cause dominant negative effect

190
Q

How does p53 cause cell cycle arrest?

A

P53 activates p21 and stops G1/S checkpoint

191
Q

How does p53 cause apoptosis?

A

Activates PUMA, NOX, Bak/bim

192
Q

What are two apoptosis pathways?

A

Death receptor and mitochondrial

193
Q

What connects the two apoptosis pathways?

A

Caspase 8

194
Q

Is E-cad high or low in aggressive tumors?

A

Low expression bc lose connection btw cells so can detach from primary

195
Q

What pathways does VEGF stimulate?

A

PI3K, BcL2

196
Q

Which VEGFR is associated with lymphatics?

A

VEGFR3 (binds VEGF B and C)

197
Q

What are endogenous pro angiogenic signals?

A

VEGF, PIGF, PDGF, TNFa, TGFb, Ang1,2 IL8

198
Q

What treatments are antiangiogenic?

A

Bevacizumab, metronomic, thalidomide, angiostatin

199
Q

What pathways synthesize Hif?

A

PI3K, mTOR

200
Q

What drugs are MDRI substrates?

A

Anthracyclins, vincas, MTX, Epipodophyllotoxins, taxanes, topotecan

201
Q

What 2 drugs can reverse pgp resistance?

A

Verapamil and cyclosporine A

202
Q

What drug classes does glutathione inactivate?

A

Doxorubicin, alkylators, platinums

203
Q

What cells express MHC I and MHC II?

A

All cells I, only APCs II, MHC III is involved in complement

204
Q

What energy pathway do most cancer cells use?

A

aerobic glycolysis, cancer cells need more gluc/ATP and produce high lactate

205
Q

What are markers for Tregs?

A

CD4, CD25, FoxP3

206
Q

What do Treg secrete?

A

TGFb, IL-10

207
Q

What is the primary immunosurveillance molecule?

A

IFN-gamma, levels should change with immune response

208
Q

Intrinsic markers of hypoxia?

A

Hif-a, GLUT-1, CAIX

209
Q

Radiation induced fibrosis due to what factor?

A

TGFB

210
Q

As you increase the amount of time to give total dose of RT, you increase which R?

A

Repopulation

211
Q

Which R results in a substantial increase in tumor sensitivity during fractionated treatment?

A

Reoxygenation

212
Q

What is the critical parameter regarding normal tissue reponse to radiation therapy?

A

Fraction size

213
Q

The L-Q model does not take into account which treatment parameter?

A

Treatment time

214
Q

What drug has been linked to a cause of pseudolymphoma in a cat?

A

Phenobarbital (reversed by switching to Keppra)

215
Q

Which is not an aminobisphosphonate?

A

Clodronate

216
Q

Which is the most potent bisphosphonate?

A

Zoledronate

217
Q

Which are prodrugs?

A

Procarbazine, Ifosfamide, Cytoxan, DTIC, dexrazoxane

218
Q

In addition to doxorubicin, this drug forms reactive oxygen species?

A

Bleomycin

219
Q

DNA vaccine in dogs against TERT did what?

A

Prolonged ST and time to first relapse and overcame tolerance in >90%

220
Q

2 prognostic factors associated with increased risk of late toxicities for pelvic RT?

A

Large trt field and perianal tumor

221
Q

P27 is highest/lowest in which phases of the cell cycle?

A

Go/late G1

222
Q

Inhibition of what pathway leads to autophagy?

A

mTOR

223
Q

Which pathway leads to inactivation of Rb via induction of cyclin D?

A

Ras

224
Q

What transcription factors are involved in EMT?

A

Snail, slug, twist, LEF

225
Q

Small molecule inhibitors for EGFR?

A

Cetuximab, Erlotinib, Gefitinib, Panitumumab

226
Q

What inhibits IAP (inhibitors of apoptosis)?

A

Smac/Diablo

227
Q

The death receptor and mitochondrial pathways are lined by which caspase?

A

Caspase 8

228
Q

Four ways to test for apoptosis?

A

Alterations in membrane fxn (Annexin V)
release of cytochrome C (IHC, or WB)
activation of caspases (WB)
fragmentation of nuclear DNA (TUNEL)

229
Q

This receptor pathway lacks intrinsic tyrosine kinase activity?

A

Cytokine R’s (use Jaks)

230
Q

Which hormone suppresses Cox?

A

Estrogen

231
Q

This pathway involves a series of cleavage events to be activated?

A

Notch

232
Q

What is cross presentation?

A

When extracelluar antigens are presented by MHC I

233
Q

Major toxicity with IL-2?

A

Capillary leak syndrome

234
Q

Major toxicity with TNF-a?

A

Septic shock syndrome

235
Q

Method of choice for detecting LOH?

A

FISH

236
Q

In addition to dendritic cells, what other immune cell expresses CD40?

A

B cells, (CD40L on Tcells)

237
Q

LFA-1 is expressed on___ and binds to ____?

A

Lymphocytes and binds to ICAM-1 on dendritic cells

238
Q

Highest levels of pgp in what two tissues?

A

Kidney and adrenal gland

239
Q

Bortezomib inhibits?

A

Proteosome

240
Q

Tipifranib is a farnesyltransferase inhibitor which results in blockade of what pathway?

A

Ras

Radiation Biology (3 decks)

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