General Questions Flashcards
1
Q
What is the most common site for canine chondrosarcoma?
A
Nasal cavity
2
Q
Is canine gastrointestinal lymphoma more commonly T or B cell?
A
T-cell (63% vs. 37% B-cell)
3
Q
Which exons are typically mutated with c-kit in feline mast cell tumors?
A
Exon 8 and 9 (extracellular domain)
65% of cats will carry this mutation (most were 8, more common with splenic MCT).
4
Q
Which gene was recently associated with MCT development in Golden Retrievers?
A
GNAI2- associated with hyaluronic acid synthesis
5
Q
How many dogs with MCT present with multiple tumors?
A
11 - 14%
6
Q
In dogs, c-kit mutations appear to be associated with _____% of intermediate and high grade MCT.
A
25 - 30%
7
Q
How many dogs with MCTs located in the muzzle present with regional metastasis?
A
50 - 60%
This does not necessarily indicate a worse long-term prognosis, as the MST for dogs with metastatic disease was 14 months.
8
Q
What is the reported MST for poorly differentiated MCT with the presence of LN metastasis?
A
194d.
VS. 503d for dogs with no metastasis.
9
Q
What is the incidence of bone marrow involvement in canine MCT?
A
2.8%
10
Q
Which parasite has been associated with development of sarcoma in dogs?
A
Spirocerca lupi
11
Q
What is the most common paraneoplastic syndrome associated with thymoma in the cat?
A
Exfoliative dermatitis
12
Q
What 3 abnormalities characterize a syndrome associated with mutation in the canine Birt-Hogg-Dube (BHD) gene in German Shepherd dogs?
A
1) Multiple uterine leiomyomas
2) Bilateral renal cystadenocarcinomas
3) Nodular dermatofibrosis
Mutation in FLCN- tumor suppressor gene coding for protein folliculin. Also seen in Alsatians.
13
Q
Which gene expression is common in canine gastric carcinoma?
A
exon 11 of c-kit gene, HER-2 (58%)
14
Q
Which testicular tumor is most often associated with hyperestrogenism?
A
Sertoli cell tumor
15
Q
Which characteristics predict a worse outcome for dogs diagnosed with B cell lymphoma?
A
Large cell, low levels of class II MHC expression
16
Q
What is the most common location of feline appendicular osteosarcoma?
A
Distal femur and proximal tibia
17
Q
Which tumor location is most suitable for limb sparing surgery in dogs affected by OSA?
A
Distal radius or ulna
18
Q
Which protein is necessary for metastasis in murine models of osteosarcoma and associated with shorter DFI in dogs with osteosarcoma?
A
Ezrin
19
Q
Which breed is predisposed to bile duct carcinoma?
A
Labrador Retrievers
Sex predilection for females.
20
Q
Which monoclonal antibody targets HER-2 positive tumors in humans?
A
Trastuzumab
21
Q
What percentage of HSA occur primarily in the liver?
A
4 - 6%
22
Q
Which virus is associated with HCC In humans?
A
Hepatitis viruses B and C
23
Q
Which cells do carcinoid cells arise from?
A
Neuroendocrine cells
Contain secretory granules that may contain substances such as 5-hydroxytryptamine (serotonin), secretin, somatostatin, and gastrin, among others. IHC for cytokeratin and serotonin may be positive.
24
Q
What histopathologic factors are associated with worse prognosis for canine SQ MCT?
A
Mitotic index > 4
Multinucleation
Invasiveness
25
What is the MST for dogs with perianal adenocarcinoma with LN or distant metastasis
7 months (however aggressive treatment was not attempted in 5/6 dogs)
26
What is the RR of AGASAC to Palladia?
25% PR, 63% SD, total clinical benefit rate = 88%
27
What is the MST of dogs with nasal carcinoma without treatment?
95 days (3 months)
28
What is the MST of cats with lymphoma without treatment?
53d
29
What % of cats treated with SRT for Functional Pituitary Adenoma developed hypothyroidism?
14%
30
Which tumors are known to express ABCB1?
Canine lymphoma, mammary tumors, feline primary pulmonary carcinoma
31
What % of dogs with testicular tumors have bilateral tumors?
50%
32
What % of dogs with sertoli cell tumors will present with signs of hyperestrogenism?
50%
33
What % of dogs will have > 1 testicular tumor type?
4 - 20%
34
What percentage of dogs with prostate tumors, when treated with a total prostatectomy, will experience permanent urinary incontinence?
35%
MST = 231 days (shorter in dogs with extracapsular invasion compared to intracapsular tumors)
35
What % of prostatic carcinomas had COX-2 expression in dogs?
75-88%
36
What is the MST of dogs with PCA treated with NSAID alone?
6.9 months
37
What % of dogs with PCA will have skeletal mets?
22 - 42%
38
What % of dogs with iUC are reported to have urethral involvement?
56%
39
What is the MST of cats with iUC treated with a variety of treatments?
261
| 11 cats treated with meloxicam = 311d. More than half were away from the trigone.
40
What % of dogs with iUC are reported to have prostatic involvement?
29%
41
What is the MST of dogs with renal HSA in a retrospective of 14 dogs?
278
42
In a phase 1 clinical trial of intravesical mitomycin C, what were the most significant complications?
Marked myelosuppression and GI upset- indicating there was some systemic absorption occurring.
43
Although neoplastic cells are often indistinguishable from reactive epithelial cells in the urine of dogs with TCC, neoplastic cells may be present in the urine in up to ___% of cases
30%
44
What % of cats with meningioma present with multiple tumors?
17%
Withrow pg. 583
45
What is the most common type of glioma in dogs?
Oligodendroglioma (previously reported to be astrocytoma)
New Withrow
46
What is the MST for dogs with CNS lymphoma treated with a variety of treatments?
171d
47
What is the MST for dogs with presumptive glioma treated with CCNU?
178d
48
What is the reported MST for cats with cerebral meningiomas treated surgically?
23 - 37 months.
685 days in another study (2 years)
49
What proportion of cerebral meningiomas in cats will recur following surgical treatment?
20.6 - 25% (median TTR 285 days)
50
What is the MST of dogs with meningioma treated surgically with conventional techniques?
7 mo.
51
What % of feline brain tumors detected incidentally?
20%
52
```
What is the most common location for spinal meningiomas and malignant nerve sheath tumors? Options are:
A) Extradural
B) Intradural/extramedullary
C) Intramedullary
D) Mixed
```
B) Intradural/extramedullary
53
Which breeds of dog are predisposed to spinal nephroblastoma at a young age?
GSD and Golden Retrievers
54
Which spinal cord segments do Nephroblastomas arise from?
T9 - L2
55
Which is the most common spinal nerve root affected by PNST?
Caudal cervical region (C6 - T2)
56
What is the most common tumor of the canine conjunctiva?
Melanoma.
| Older, female, Weimaraner and possibly GSD/large breed dogs may be predisposed.
57
What is the most common tumor of the third eyelid in dogs and cats?
Adenocarcinoma (85%)
58
What is the average latency period for cats to develop ocular posttraumatic sarcoma?
5 years
| 67% are males or neutered males.
59
In cats with orbital neoplasia, what % had radiographic signs of orbital bone lesion?
59%
| --> 15% had pulmonary metastasis
60
What percentage of canine anterior uveal melanomas demonstrate metastasis?
25%
61
What % of conjunctival melanoma recur following excision?
55%
| at least 17% of the dogs experienced orbital invasion or spread to the regional lymph nodes or lung
62
What percentage of dogs with large B-cell lymphoma will have normal CBCs but exhibit bone marrow involvement when assessed via flow cytometry?
15%
63
What is the characteristic marker for T-zone lymphoma?
CD45-
64
What was the MST of T-zone lymphoma in Seelig et. al 2014?
657d
65
What % of normal canine lymphocytes in peripheral circulation are T cell and B cell respectively?
T cell = 80%
B cell = 15%
NK and double negative T cell = 5%
66
In retrospective study by Childress et. al, what were the 4 negative prognostic factors identified in dogs with DLBCL undergoing CHOP chemotherapy?
1) Thrombocytopenia
2) Greater age at diagnosis
3) Higher neutrophil count
4) Higher serum globulin concentration
67
What is the sensitivity and specificity of US for detection of hepatic involvement of lymphoma?
```
Sensitivity = 73%
Specificity = 81%
```
68
What is the sensitivity and specificity of US for detection of splenic involvement of lymphoma?
```
Sensitivity = 100%
Specificty = 23%
```
69
Which breed has been described to have lymphocytic-plasmacytic inflammatory bowel disease that progressed to GI lymphoma?
Basenji
70
Which dog breeds may be overrepresented in cases of alimentary lymphoma?
Boxers and Shar-pei
71
What % of dogs with lymphoma present with hypercalcemia?
10 - 40%
72
What is the name of the syndrome of cutaneous T-cell epitheliotropic lymphoma progressing to circulating malignant cells in humans?
Sezary syndrome
73
What chromosomal aberration has been detected in dogs with naturally occurring lymphoma and appears to hold prognostic significance?
Chromosome 13
Gains of canine chromosomes 13 and 31 and loss of chromosome 14 have been documented as the most common aberrations in a group of 25 cases analyzed.
→ prognostic advantage in dogs with trisomy chromosome 13 has been identified.
74
What % of dogs with multicentric lymphoma have diffuse pulmonary infiltration?
27 - 34%
75
What percentage of dogs with multicentric lymphoma are expected to go into complete remission when treated with single agent doxorubicin as a first line therapy?
50 - 75%
MST 6 - 8 months
76
For dogs that have completed the CHOP chemotherapy protocol for lymphoma, what percentage of dogs will successfully be reinduced by the same protocol >2 months after completion of treatment?
80 - 90%
77
What is the most common lymphoma-related paraneoplastic syndrome?
Anemia
78
What % of dogs with lymphoma will have ocular involvement/uveitis?
33 - 50%
79
What % of dogs with lymphoma are reported to have monoclonal gammopathies? Which type of lymphoma?
6%
| Usually B-cell lymphoma
80
What are the B-cell markers?
CD79a, CD20, CD21, Pax5
| --> Although dogs with TZL can express CD21
81
What are the T-cell markers?
CD3 (pan), CD4 (helper), CD8 (cytotoxic)
82
What classifies as a LARGE lymphocyte?
>2x an RBC or larger than a neutrophil
Intermediate = 1.5-2x RBC, same size as neutrophil
83
What percent of dogs with multicentric lymphoma exhibit radiographic evidence of a cranial mediastinal lymphadenopathy at the time of diagnosis?
20%
84
What percentage of dogs with hypercalcemic lymphoma will have mediastinal involvement?
43%
85
What is the overall response rate for DTIC when used in the rescue setting for canine multicentric lymphoma?
35% (response duration of 43d)
86
PARR sensitivity and specificity for canine lymphoma?
70 - 90% sensitivity, 5% false positive rate (95% specificity). False positives occur in some infectious diseases (ehrlichiosis and leishmania)
87
What is the name of the monoclonal antibody against CD20 used in humans with B-cell NHL?
Rituximab
88
What is the MST for colorectal lymphoma in dogs receiving chemotherapy and what is the dominant immunophenotype?
MST = 1845 - 2352
| B-cell
89
What is the reported MST of dogs with low grade GI lymphoma treated with chlorambucil and prednisone?
1.5 - 2 years
90
What is the response rate for cutaneous lymphoma to chemotherapy?
40 - 80%. Median remission duration = 3 - 6 months.
91
What percentage of senior Golden Retrievers without evidence of lymphoproliferative disease have TZ cells (CD45- T cells) in peripheral blood when analyzed by flow cytometry?
31%
92
Approximately what percentage of dogs with T-zone lymphoma have been reported to be Golden Retrievers?
40%
93
What is the median PFI and Overall ST for canine nodal marginal zone lymphoma?
PFI = 5 months
| Overall ST = 8.5 months
94
What is the median PFS for cutaneous lymphoma treated with Tanovea?
38d
95
What is the response rate and median remission duration for cutaneous lymphoma treated with CCNU?
80%, median remission duration = 3 months
96
What is the concordance rate of pre-treatment bx STS to final dx?
59%
| 29% underestimate, 12% overestimate
97
What was the MST for dogs treated with surgery and adjuvant carbo for oral melanoma (+/- RT)?
```
MST = 440d
PFI = 259d
```
98
What percentage of dogs with chronic lymphocytic leukemia were reported to develop Richter’s syndrome?
5%
| Median survival = 41d
99
Normalization of lymphocyte counts occur in what % of treated CLL cases?
70%
100
In a study of metastatic cancer of unknown primary, what % were diagnosed as carcinoma?
57%
MST = 30 days
Primary site not identified on full body CT in 95% of dogs
101
What proportion of telangiectatic OSA were reclassified as HSA of bone when stained with VWIII-related antigen or VWf?
20%
102
In a study of 40 dogs with systemic mastocytosis, which chemotherapy protocol provided the best outcome?
Lomustine + Vinblastine + Pred MST = 227d
| Palladia MST = 118d
103
What was the MST for feline large granular lymphoma receiving a variety of treatments?
```
MST = 21d
small subset (7.3%) survived > 6 months.
MST was significantly shorter in the case of substage b, circulating neoplastic cells, lack of chemotherapy administration, and lack of treatment response.
```
104
Which chemotherapeutic drugs are inhibitors of ribonucleotide reductase?
Gemcitabine, Cytarabine, Hydroxyurea --> reason for radiation sensitivity?
105
What % of cats with renal transplant receiving cyclosporine developed neoplasia in Wormser et. al 2014?
22.5% (56% of which were lymphoma--> 10 - 13%)
106
Compared to the control population, renal transplant cats have a _____ times higher odds of developing malignant neoplasia and a _____ times higher odds of developing lymphoma.
6. 6x neoplasia
| 6. 7x lymphoma
107
What % of cats with T-cell GI lymphoma exhibit epitheliotropism?
40%
108
What % of cats with lymphoma have pulmonary involvement?
12.8%
56. 2% had no gross abnormalities. (peribronchial-vascular invasion most common histo abnormality)
87. 5% were B-cell vs. T-cell
37. 5% + FeLV
109
What is the immunophenotypic classification for Hodgkin's like lymphoma in cats?
T-cell rich B-cell lymphoma
110
Nasal lymphoma in cats are primarily what phenotype?
68% B-cell (20% T-cell, 12% mixed)
111
Renal lymphoma in cats in Australia are primarily what phenotype?
B-cell
112
What % of cats with renal lymphoma will have extension to the CNS?
40 - 50%
113
What % of CNS lymphoma in cats are part of a multicentric disease?
80%
114
What % of CNS lymphoma are FeLV + antigenemic?
17 - 50%
115
Which area of the spine most commonly affected by CNS lymphoma
thoracolumbar
116
What % of hypercalcemic cats are diagnosed with lymphoma?
10%
117
What is the reported sensitivity of PARR for feline lymphoma?
80%
| Specificity has not been established.
118
What % of cats with LGL (6/8 were treated with CHOP) were reported to live longer than 6 months?
7.3%
119
What is the reported MST of cats with LGL treated with chemotherapy?
63d (2 months)
120
Methylation of the promoter region of p16 has been identified in ___% of feline B-cell lymphoid tumors
33%
121
What is the reported sensitivity and specificity of splenic ultrasonographic appearance (i.e., a moth-eaten parenchyma) for the diagnosis of feline malignancies?
Sensitivity = 13.2%
Specificity = 84.8%
Splenic mass >1cm sens = 21%, spec = 94.7%
122
Post-chemotherapy bowel perforation has been reported in cats with high grade gastrointestinal lymphoma. Which variable was associated with increased risk of perforation?
Magnitude of weight loss within 15 - 28 days of diagnosis
123
What is the increased risk associated with FeLV cats in developing lymphoma?
62x
FIV infection associated with 5x risk
124
Mast cells can be seen in up to ___% of aspirations from thymoma?
50%
125
What % of renal lymphoma will be bilateral?
>80%
126
What % of renal lymphoma will have US evidence of other organ involvement?
33%
127
What % of cats who relapsed following COP based protocol subsequently responded to single agent DOX?
22%
128
What was the response rate for cats with lymphoma treated with L-Spar?
30%
| Much shorter asparagin-depleting effect in cats (lost by 7 days)
129
A bone marrow aspirate with greater than ____% abnormal blast cells is sufficient to make the diagnosis of acute leukemia in cats.
30%
27% CR to COP based protocol
130
In cats with suspected CLL, infiltration of the bone marrow with more than ____% mature lymphocytes helps confirm the diagnosis.
20%
Most are of T-cell lineage and most are FeLV negative.
131
ALL in cats is primarily what phenotype?
T-cell
| About 60 - 80% FeLV positive
132
What phenotype is most common with Mediastinal Lymphoma?
T-cell
| Nasal = B-cell
133
What is the reported MST of 20 cats with high-grade GI LSA when treated with surgical resection and CHOP-based chemotherapy?
420d
134
Nasal lymphoma immunophenotype?
3/4 B-cell
135
What is the median survival time for FeLV-positive cats with mediastinal lymphoma?
2-3 months
| Young FeLV-negative Siamese cats with mediastinal lymphoma had durable responses of ~9 months
136
What % of cats with lymphoma will respond to L-asparaginase?
30%
137
Missense mutations in what genes have been identified in dogs with AML?
FLT3, C-KIT, RAS
138
What is the tendency for the myeloid:erythroid ratio to be in Polycythemia vera?
Normal
139
What are the markers for megakaryocyte lineage in dogs and cats?
Acetylcholinesterase, vWF/fVIII, platelet glycoprotein, CD41
140
What are the markers for neutrophils?
peroxidase, Sudan Black B, chloracetate esterase
141
What are the markers for monocytes?
Nonspecific esterases (alpha-naphthyl acetate esterase or alpha-naphthyl butyrate esterase), especially if they are inhibited by sodium fluoride
142
What is the marker for basophils?
Omega exonuclease, + for chloracetate esterase activity.
143
What are the markers for myeloid cells?
MPO and CD11b
144
What is the most common type of DNMT3L (methylation) mutation identified in dogs with AML?
Missense mutation in exon 7
145
What disorders are known to cause secondary thrombocytosis?
Iron deficiency anemia, chronic inflammatory diseases, recovery from severe hemorrhage, rebound from ITp, and absence of a spleen.
146
You are treating a dog with chronic myelogenous leukemia. After inducing with hydroxyurea (20mg/kg twice daily), what hematologic parameter is used to gauge your dose reduction?
Leukocyte count falls to 15,000 - 20,000 cells/uL
147
Philadelphia chromosome or BCR-ABL translocation between chromosomes 9 and 22 in humans with CML. What are the equivalent chromosomes in dogs with CML?
Chromosomes 9 and 26
148
What % of dogs with MM will have abnormal PT/PTT?
50%
149
HVS occurs in what % of dogs with MM. Which immunoglobulin is most frequently associated with this?
20 - 40% (IgM)
150
What % of dogs with MM develop Bence Jones proteinuria?
25 - 40%
151
What are the known negative prognostic factors in dogs with MM?
Hypercalcemia
Bence Jones proteinuria
Extensive bony lysis
152
Which IHC stains are typically used for EMP?
MUM-1, IRF-4, thioflavin T
153
When is staging most important for EMP?
Cutaneous plasmacytosis, SOP, GI EMP (higher risk of metastasis)
Less important for cutaneous, oral, and colorectal plasmacytoma
154
What % of cases with cutaneous plasmacytosis had LN or abdominal visceral involvement?
30%
155
What is the recurrence and metastatic rate for solitary cutaneous and oral plasmacytomas following surgery?
5% and 2% respectively
156
What is the MST for colorectal plasmacytoma treated with surgery +/- chemo?
15 months
157
What is the MST for Waldestroms macrogammaglobulinemia (IgM) treated with chlorambucil?
11 months, 77% RR
158
What % of dogs had concurrent splenic and right atrial HSA on echocardiogram in one study?
8.7%.
| Previous necropsy studies suggest about 25%
159
What are the IHC markers for hemangiosarcoma?
VWf/fVIII-related antigen or CD31/platelet endothelial cell-adhesion molecule
160
What % of grossly abnormal livers in dogs with confirmed splenic HSA were confirmed to contain HSA metastasis in one study?
50%
161
What is the MST for primary renal HSA?
9 months
162
What is the MST for retroperitoneal HSA?
37.5d
163
What is the MST for dogs treated with Splenectomy + AC + L-MTP-PE?
273d (9 months)
164
What % of dogs with HS have clinicopathologic changes consistent with DIC?
50%
165
What % of dogs with Thymoma are reported to have paraneoplastic syndromes?
67%
| --> 40% ME with associated aspiration pneumonia
166
What % of dogs will have a concurrent 2nd tumor with Thymoma?
27%
167
Hypofractionated radiation therapy has been described as a treatment for non-resectable canine thymoma. What was the reported median time to response following treatment initiation?
22d
168
What is the % of perioperative mortality in dogs and cats undergoing excision of thymic epithelial tumors?
```
Dogs = 20%
Cats = 22%
```
169
Which histologic factors were more common with atypical thymoma and thymic carcinoma compared to thymomas?
Pleomorphism, mitotic figures, capsular invasion, and higher stage disease.
IHC (GLUT-1, CD5, CD117, CK8/18) was not useful.
170
With TVT if regression is going to occur, at what time is this typically seen?
Within 3 - 9 months
171
What % of TVT metastasize?
5 - 17%, to regional LN or elsewhere.
172
What are the IHC markers for TVT?
1) Vimentin
2) Lysozyme
3) Alpha-1-antitrypsin (AAT)
4) Macrophage-specific ACM1
173
Oncogenesis of TVT involves which 2 genes?
LINE-c-myc and p53
174
What is a reported paraneoplastic syndrome of TVT?
Erythrocytosis
175
What is the reported metastatic rate for TVT?
<15% (but might be higher as many are not staged)
176
What is the response rate of TVT to vincristine chemotherapy?
90 - 95%
177
What is the recurrence rate of TVT following surgical removal?
30 - 75% (marginal surgical excision not effective)
178
TVT’s are unlikely to spontaneously regress after how many months?
9 months
179
Which tumor suppressor genes are inactivated with mesothelioma?
cyclin-dependent kinase inhibitor 2A (CDKN2A), BRCA1 associated protein 1 (BAP1), and neurofibromin 2 (NF2)
180
Sclerosing mesothelioma is associated with what signalment?
Male German Shepherds
181
Which gene is mutated with renal cystadenocarcinoma and nodular dermatofibrosis?
Birt-Hogg-Dube (BHD) gene.
The BHD gene codes for the tumor suppressor protein folliculin and mutations in this gene are thought to lead to loss of function. This disease is primarily seen in German Shepherd dogs. Also see uterine leiomyomas.
182
Which mutation is most common with Chronic Myelogenous Leukemia in humans?
Philadelphia chromosome or BCR-ABL translocation between chromosomes 9 and 22. The analogous chromosomes in dogs are chromosomes 9 and 26, and BCR-ABL translocation, termed "Raleigh chromosome," has been reported in several cases of CML in dogs.
183
Most common mutation in canine and feline SCC
p53
184
Which of the following has been shown to be a negative prognostic factor for canine HS?
Palliative therapy, disseminated HS, and concurrent use of corticosteroids
(Dervisis et. Al, 2016, VCO)
185
Which drugs have been associated with radiation recall?
doxorubicin, taxanes, gemcitabine
186
In the 2016 paper by Giuffrida et. al, what % of tumors were reclassified on the basis of FVII-RAg/vWF immunoreactivity, from an original diagnosis of telangiectatic OSA to HSA?
20%
187
What is the most common phenotype for Canine CLL?
T cell origin (CD3+, CD21-)
| CD3+, CD4-, CD8+ (73% in one study, 91% in another)
188
What percentage of cats with acromegaly were male in SRT paper for feline acromegaly? (Wormhoudt et al. 2018)
80%
189
In a recent study on IHC for nasal carcinoma and lymphoma in cats, what % of samples required IHC to differentiate carcinoma from lymphoma?
7%
190
Markers for Feline progressive histiocytosis?
CD1a, CD11c/CD18, CD5, Iba-1, CD204
191
Which IHC markers are used to distinguish pheochromocytoma from adrenocortical carcinoma?
chromogranin A and synaptophysin
192
GIST IHC markers?
CD117, Dog-1, CD34, and SMA (+/-).
| Desmin and S-100 NEGATIVE
193
Which IHC markers are positive with hemangiosacoma?
Factor VIII (vWF), CD31/PECAM-1
194
Which IHC marker can confirm a diagnosis of hemophagocytic histiocytic sarcoma?
CD11d
195
Which IHC stain can differentiate between canine urinary bladder transitional cell carcinoma and other carcinomas?
Uroplakin III- expressed in more than 90% of canine TCC.
196
IHC markers for MCT?
Vimentin (+)
Tryptase and CD117 (KIT) (+)
+/- chymase, MCP-1, and IL-8 (+)
197
IHC marker for Thyroid carcinoma (c-cell)
Synaptophysin (+) chromogranin (+) thyroglobulin (-)
198
IHC marker for Thyroid carcinoma (epithelial)
Thyroglobulin (+)
199
What are the IHC markers for Melanoma?
Melan-A, PNL2, Tyrosinase-related protein (TRP)-1 and TRP-2 +/- S-100, human melanoma black 45 (HMB45)
200
Feline cutaneous MCT response to Lomustine?
20 cats: 2 CR, 8 PR = 50% ORR
201
Which anthracycline may be administered orally?
Idarubicin
202
What toxicity is associated with 5-FU in cats?
Fatal CNS toxicity
203
Why is cyclophosphamide relatively platelet sparing?
High levels of aldehyde dehydrogenase in the bone marrow (which deactivates cyclophosphamide)
204
Which chemotherapy drugs are severe vesicants?
Doxorubicin, vinca alkaloids, mechlorethamine, actinomycin D
205
What is the active metabolite of cyclophosphamide?
Phosphoramide mustard
206
Which drugs are radiation sensitizers?
Carboplatin/cisplatin, actinomycin D, gemcitabine, 5-FU, etanidazole, metronidazole (+\- Dox)
207
What are the solvents used for paclitaxel and docetaxel respectively that allow for IV administration?
```
Paclitaxel = Cremophor EL
Docetaxel = Polysorbate 80
```
208
Which enzyme functions in alkylator-induced DNA repair (eg. Temozolomide)
MGMT (O6 methylguanine DNA methyltransferase)
Removes adducts from the O-6 position of guanine and transfers the alkyl group to a specific cysteine residue (acceptor site) on the enzyme--> renders it inactive
209
What is the reported MST for dogs with stage IV MCT?
Pizzoni et. al VCO 2018
110 days
Tumor diameter >3cm and more than 2 metastatic sites, BM infiltration, and lack of tumor control at primary site were negative px factors.
210
Which breed is predisposed to Cutaneous Langerhans Cell Histiocytosis?
Shar-Pei (35%)
- Onset of regression can take up to 10 months
- 50% euthanized due to lack of regression
- LN metastasis--> no regression
211
What are the markers for reactive histiocytosis?
CD1a, CD11c, MHC class II, Thy-1 (CD90), and CD4 but NEGATIVE for E-cadherin.
Histiocytoma is NEGATIVE for Thy-1 and CD4 but POSITIVE for E-cadherin
CD1a, CD11b, CD11c, MHC class II can only be done on fresh smears or snap-frozen tissues.
212
What cell type or cytokine is thought to mediate the regression of cutaneous histiocytoma?
CD8+ T-cells
213
Which Tumor Suppressor gene most commonly mutated with HS?
CDKN2A/B
Also RB1 and PTEN
214
Why is p53 often present in high concentrations in tumors that carry mutant, defective p53 alleles?
Mutant p53 loses its transcription activating powers, unable to induce Mdm2 transcription. In the absence of Mdm2, p53 escapes degradation and accumulates.
215
Genetic instability in patients with hereditary nonpolyposis colon cancer occurs because of a deficiency in which DNA damage repair pathway?
Mismatch repair (MMR)
216
What is the definition of Linear Energy Transfer?
The average energy lost by a particle over a given track length.
217
What % of dogs with MCT had GI ulceration on necropys?
35 - 83%
218
Prognosis for dogs with MCT with bone marrow involvement?
43d
219
What are the markers for MCT?
vimentin (+), CD117+, chymase, MCP-1, IL-8
220
What % of tissue shrinkage will occur for cutaneous tumors following formalin fixation?
30%
221
What is the ORR for Paccal Vet for canine MCT?
59%
222
Negative prognostic indicators for feline splenic MCT?
Anorexia, significant weight loss, and male gender.
223
What are the top 3 most common intestinal tumors in the cat?
1) Lymphoma
2) Adenocarcinoma
3) Mast cell tumor
224
Tumor cells located further than approximately ___um from vessels experience "diffusion-limited" hypoxia as oxygen is consumed by the tumor cells more proximal to the vessels.
100um
Tannock pg. 278 (5th edition, newer edition says 150um)
225
What are some of the markers of Cancer stem cells?
CD34 - AML
CD44 - Breast Cancer
CD133 - Glioma
226
Dogs with MM caudal to PM3 are ____ times more likely to die from tumor related causes compared to dogs with tumors rostral to PM3.
4.3
Dogs with incomplete histo margins 3.6 x more likely to die of tumor-related causes.
227
What percentage of dogs with digital melanoma are reported to have metastasis at the time of diagnosis?
30 - 40%
228
What is the MST of dogs with melanoma of the digit without lymph node or distant metastasis treated with digit amputation?
12 months
229
What % of dogs with oral malignant melanoma will experience a complete remission when treated with RT?
51 - 69% (up to 70% according to new Withrow)
ORR = 82 - 94%
Dogs with tumors <5cm^3 were more likely to achieve a CR
230
What % of dogs with normal size lymph nodes and OMM had LN mets?
40%
231
What % of dogs with oral melanoma treated with RT will develop bone necrosis?
8%
232
What is the local recurrence rate of dogs with microscopic disease of oral melanoma after incomplete surgical resection and radiation therapy?
26%
vs. 45% for those treated with RT in macroscopic disease setting.
233
What are the local recurrence rates for mandibulectomy and maxillectomy of OMM respectively?
22% = mandibulectomy
48% = maxillectomy
MST with surgery alone = 150 - 318d, with 1-year survival <35%
234
Melanoma typically is considered to have a high or low alpha beta ratio?
LOW- higher dose/fraction
Tumors that may have a lower a/B ratio include melanoma, prostatic tumors, STS, TCC, and OSA.
Withrow pg. 183 (2013)
235
In a study of 5 cats treated with RT for oral melanoma, what was the ORR and MST?
ORR = 60%, MST = 146d
One cat treated with carbo, one with carbo + mito, one with melanoma vaccine.
236
What is the sensitivity and specificity for Ki67 >19.5% to identify tumor related death due to OMM at 1- year?
```
Sensitivity = 87%
Specificity = 85%
```
237
White cats in California are ___ times more likely to develop SCC
13.4
238
When PCR is used to amplify papillomavirus DNA, up to what % of UV-protected SCC are positive?
76%
42% in SCC in regions exposed to UV radiation.
239
What breeds are associated with multiple digital SCC?
Large breed dogs with black skin and haircoat: Standard Poodles, Black Labradors, Giant Schnauzers, Gordon Setters, Rottweilers. +/- Dachschund, flat coat retriever.
240
Which breed is predisposed to digit melanoma?
Scottish Terriers
241
What is the reported disagreement rate between pathologists when evaluating digital masses?
20%
242
What % of canine SCC were positive for p53 overexpression?
30%
47.5% in feline SCC.
243
What mutation was found with 100% of trichoepithelioma and pilomatricomas?
B-catenin
244
What % of canine and feline SCC were + for cyclin A?
44% canine
90% feline
Cyclin D was rarely expressed in skin tumors of any type.
245
Which marker is highly specific for BCC and helps to differentiate it from SCC or cystic-solid ductular tumors in the diagnosis of BCC in humans?
BerEP4
+/- Cytokeratin 8
246
Which breeds are at increased risk for BCC in one study?
Cocker Spaniels, Poodles
247
What are the 3 histo subtypes of BCC?
Solid, keratinizing, clear cell
248
Which drug has been shown to be effective in treating multiple papillomas?
Azithromycin
249
What is the name for when SCC in situ appears in multiple sites?
Bowen's carcinoma or
Bowenoid carcinoma in situ (BISC) OR
Multicentric papillomavirus-induced SCC.
250
What is the name used for SCC in situ that arises as a consequence of UV exposure?
Actinic keratosis
Occurs in lightly haired skin with UV exposure, can occur as a solitary lesion. It is typically accompanied by solar elastosis and fibrosis of the skin, consistent with the effects of chronic UV exposure.
Highly positive for p53 expression compared to BISC.
251
Which chromosome and gene is the effector transcription factor of hedgehog signaling cascade and has been reported to be associated with canine basal cell carcinoma?
Chromosome 10, GLI1 gene.
252
What % of dogs with digital SCC have bone lysis on radiographs?
80%
| 8.8% have metastasis at presentation, 23.2% eventually develop metastasis
253
What are the 2 immunosuppressive molecules expressed by T-reg cells and activated T-cells and are the targets of check point inhibitors?
CTLA-4 and PD-1
254
Mechanism of action of Imiquamod?
Activates TLR7
Has been used to treat BISC in 12 cats, 42% CR.
255
What % of grade III PNST will invade the spinal cord?
50%
256
What % of dogs develop recurrence following hypofractionated RT for incompletely excised STS?
21%
257
What histologic subtype of rhabdomyosarcoma has a predilection for the urinary bladder in young, female, large-breed dogs?
Botryoid
St. Bernard possibly overrepresented. Grapelike appearance. In humans alveolar histotype has the worst prognosis and botryoid has the best.
258
What % of dogs with GI leiomyosarcoma will have intestinal perforation with localized to diffuse peritonitis?
50%
50% metastatic rate.
259
What is the signalment and location most commonly seen with GI Leiomyoma?
Male predisposition, predilection for the stomach.
260
Three paraneoplastic syndromes seen with GI leiomyoma and leiomyosarcoma?
1) Hypoglycemia
2) Nephrogenic Diabetes Insipidus
3) Secondary erythrocytosis
261
Which histologic type of Liposarcoma has the highest metastatic rate? Options are: well-differentiated, myxoid, poorly differentiated (round cell), pleomorphic, or dedifferentiated.
Pleomorphic
262
What are the IHC that help differentiate Lymphnagiosarcoma from Hemangiosarcoma?
LYVE-1 and PROX-1
263
MST of Liposarcoma with wide excision?
1188 days
264
MST of Liposarcoma with marginal excision?
650 days
265
MST of dogs with GIST or Leiomyosarcoma with metastasis?
21.7 months (37.4mo. without)
However other reports found metastasis significantly decreases survival time to much less than 21.7 mo
266
MST for dogs with splenic leiomyosarcoma
8 months
267
In one retrospective study of dogs with incompletely resected STS who underwent re-excision, how many had histologic evidence of residual tumor?
22%
268
What is the recurrent rate for grade II incompletely excised STS?
34% (7% for grade 1 and 75% for grade III).
269
Cumulative doses higher than ____ Gy are recommended for incompletely excised STS and local tumor control is better with higher cumulative doses.
50 Gy
270
What is the median time to local recurrence for STS in dogs?
1 year (368 days)
271
In a study of 39 dogs with incompletely excised STS treated with orthovoltage and doxorubicin as a radiation sensitizer, what MI was associated with higher risk of local tumor recurrence and shorter survival time?
Mitotic rate greater than 9/10 HPF
272
What is the median time to metastasis for dogs with STS?
1 year (365 days)
273
What is the MST for dogs with STS MI > 20?
236d (5x more likely metastasis, 2.8x more likely tumor-related death.
274
What are some of the markers for FISS?
PDGFR, EGF, TGF-B, C-jun, p53
275
What % of cats with FISS will have grade 3 tumors?
60% (only 5% grade 1)
276
What is the bluish-gray foreign material that has been identified in the macrophages in peripheral inflammatory cell infiltrates associated with FISS?
Aluminum and oxygen
Aluminum hydroxide is one of several adjuvants used in currently available feline vaccines.
277
With FISS, how much does the volume of tumor increase based on contrast-enhanced CT compared to calipers on physical exam?
TWICE
278
What % of FISS will recur following surgery and RT?
28 - 45%
279
Hi-Low oral FSA tends to occur in what anatomical location?
Hard palate and maxillary arcade between the canine and carnassial teeth.
Large-breed dogs.
280
How much of the cortex needs to be destroyed before bone lysis is evident on radiographs?
40%
281
What is the overall reported metastatic rate for MTB?
58%
282
Which breeds is canine oral eosinophilic granuloma suspected to be heritable in?
Siberian husky and Cavalier King Charles
283
What is the MST of dogs with oral melanoma <2cm with no evidence of metastasis treated with surgery?
511 days
284
What are 3 main negative prognostic indicators for dogs with oral melanoma?
1) Non rostral location
2) Bone lysis
3) Macroscopic disease
No risk factors MST = 21 months,
1 risk factor MST = 11 months
2 risk factors MST = 5 months
All risk factors MST = 3 months
285
What is the most common location for Oral SCC in dogs?
Rostral mandible
286
What paraneoplastic syndrome has been reported with Spirocerca lupi associated esophageal sarcoma?
Hypertrophic osteopathy
Usually affects the caudal thoracic esophagus, can be associated with thoracic spondylitis, microcytic hypochromic anemia and a neutrophilia.
287
Which test may aid in the diagnosis of spirocerca lupi associated esophageal sarcoma?
Fecal flotation test
288
Loss of which protein expression is associated with pancreatic carcinoma (especially poorly differentiated)
Claudin-4 and Claudin-5
289
Which breeds are predisposed to gastric cancer?
Belgian shepherds
Norweigian lundehunds
Dutch Tervueren shepherds
Males more commonly affected
290
Which tumor has been reported to metastasize to the testes?
Gastric and intestinal adenocarcinoma
291
What is the reported rate of metastasis at necropsy for Gastric Adenocarcinoma?
70 - 80%
292
Where do gastric leiomyomas occur most commonly?
Cardia
293
Where do gastric adenocarcinomas most commonly occur?
Lesser curvature and Pyloric antrum
294
What % of dogs with HCC have additional tumors?
20%- most were benign and endocrine in origin.
295
Which signalment may be overrepresented for HCC?
Male, Miniature Schnauzers
296
What is the metastatic rate for massive HCC?
0 - 37%
297
What cells do neuroendocrine tumors arise from?
Neuroectodermal cells
298
What histochemical stain is used to differentaite neuroendocrine tumors (carcinoids) from carcinomas?
Silver stain
Withrow pg. 407
299
What is the most common type of primary liver sarcoma in dogs? cats?
```
Dogs = Leiomyosarcoma
Cats = Hemangiosarcoma
```
300
Which tumor can be identified with the Grimelius histochemical stain?
Neuroendocrine tumor (Pascual’s, Grimelius, Sevier-Munger)
301
What % of dogs and cats undergoing liver lobectomy require blood transfusion?
```
Dogs = 17%
Cats = 44%
```
Hanson et. al JAVMA 2017
302
Which cat breed is 8x more likely to develop intestinal adenocarcinoma?
Siamese
303
Most commonly reported signalment for Intestinal MCT in the dog?
Male Maltese
304
Which tumors are most likely to develop in the cecum?
Leiomyosarcoma or GIST
305
What cells do GIST arise from?
Multipotent stem cells phenotypically similar to Interstitial cells of Cajal
306
What % of previously diagnosed leiomyosarcomas in the dog were reclassified as GIST using IHC for CD117/KIT?
66%
| and only 7% of GIST metastasized.
307
Where do leiomyomas most commonly occur?
Stomach
308
Which tumor was reported in association with paraneoplastic alopecia and Cheyletiella infection?
Intestinal carcinoma with abdominal carcinomatosis
309
What paraneoplastic syndrome is seen in dogs and cats with intestinal T-cell lymphoma? What is the proposed cause?
Hypereosinophilia and eosinophilic tumor infiltrates.
| Suggested cause is IL-5 secretion by the neoplastic lymphocytes
310
Which GI tumor was associated with a paraneoplastic syndrome of erythrocytosis and erythropoietin mRNA protein production by tumor cells?
Cecal Leiomyosarcoma
311
What clinicopathologic abnormality is detected in up to 85% of cats with nonlymphomatous intestinal tumors?
Elevated ALP
312
What paraneoplastic syndrome has been reported in dogs with rectal tumors?
Neutrophilic leukocytosis
313
What breeds may be predisposed to perianal adenoma?
Cocker Spaniels, Beagles, Bulldogs, and Samoyeds.
314
Which breed may be predisposed to anal sac adenocarcinoma?
English Cocker Spaniel
| In male dogs--> neutering may increase risk.
315
What is the rate of metastasis for Perianal Adenocarcinoma?
15%
Possibly occurs later in the course of disease?
316
What is the overall incidence of bilateral anal sac adenocarcinoma (either simultaneous or temporally separated)?
14%
317
What is the overall incidence of hypercalcemia with AGASACA?
27%
318
In a study of dogs with splenic mass based on body weight, which were more likely to be diagnosed with HSA?
>27.8kg
319
What is the most common immunophenotype for canine chronic lymphocytic leukemia?
CD8+ T cell
320
What % of normal lymphocytes are CD8+ T cell?
25 - 35% (compared to 5 - 20% for B-cell)
321
Which bacterial infection can result in expansion of a phenotypically homogenous population of lymphocytes, making it difficult to distinguish from neoplasia?
E canis- expansion of CD8+ T cells that have LGL morphology
| Anne Avery, VCP 2004, Molecular methods to distinguish reactive and neoplastic lymphocyte expansions
322
Which molecular test has been developed to identify differences between chromosomes in different cells by detecting amplifications or deletions of segments of DNA (eg. gains and losses in chromosome number)?
Comparative Genomic Hybridization
323
Which assay is most often used to identify HER2 status of breast cancers and N-myc amplification in neuroblastoma?
FISH
324
After a certain number of population doublings cells undergo senescence and cease dividing although generally retaining viability. This is referred to as ______?
The Hayflick Limit
325
What is the name of the statistical adjustment that helps alleviate the risk of detecting a difference due to chance alone (type I error) when analyzing large numbers (eg. 10,000 genes in 20 patients) by dividing the threshold p-value by the number of tests to be performed?
Bonferroni correction
326
What is the name of the statistical adjustment that controls the percentage of tests that will be expected to be false-positives and provides an adjusted p-value (q-value)?
False-discovery rate
327
What is the name for the descriptive epidemiology term that refers to the number of new cases of a disease observed in a defined population in a specific time period divided by the population size?
Incidence rate
328
What is the name for the descriptive epidemiology term that refers to the number of deaths caused by the disease during a specific time period divided by the population size?
Mortality rate
329
Which term is used to describe the number of deaths caused by a specific disease in a defined population divided by the number of individuals who have been diagnosed with that particular disease, in a fixed time interval?
Case fatality rate
330
What is the term used to describe the proportion of a population that has a disease at a specific time point, (cases divided by population size) where cases include both new cases of disease and the number of previously diagnosed cases who are still alive in a population?
Prevalence
Prevalence is affected by the mortality of the disease, for example: although lung cancer is one of the most common cancers, its prevalence ranks lower then that of prostate or breast cancer because lung cancer is such a lethal disease. Cancer incidence may better reflect how commonly cancer develops in a population.
331
What is the term used to describe the risk in a group exposed to a potential disease-related factor and compares it to the risk in a group that is not exposed (or has lower exposure) to the factor.
Relative Risk
332
What is the most probable cellular outcome following DNA damage?
Repair of the damage by DNA repair enzymes
333
During which phases of the cell cycle does Homologous End recombination work?
S and G2
334
In which type of DNA repair is BRCA1 and BRCA2 important?
Homologous end recombination
335
Which DNA repair pathway typically suppresses micro-satellite instability?
Mismatch Repair (MMR)
Mutations in MMR associated with Hereditary Nonpolyposis Colon Cancer typically causes micro-satellite instability.
336
Which phosphorylated protein has been shown to be a reliable surrogate marker for DNA double strand breaks (DSBs) in cells?
Histone yH2AX
337
RAD52 is associated with which DNA repair pathway?
Homologous recombination
338
KU70/80 proteins are associated with which DNA repair pathway?
Nonhomologous end joining (NHEJ)
339
What is the approximate agreement rate between MRI and CT for staging dogs with nasal tumors?
5/6 were in agreement (83%)
Though MRI resulted in a higher tumor volume (median 18%) in 5/6 dogs and greater likelihood of detecting meningeal involvement.
340
Which cytokine is believed to be involved in inducing radiation fibrosis?
TGF-B
341
Which 2 rare paraneoplastic diseases have been reported with nasal tumors in dogs?
Erythrocytosis and hypercalcemia
342
Bilateral carotid artery ligation can palliate the symptoms in dogs with nasal tumor related epistaxis for up to ____ months or longer.
> 3 months.
343
What % of dogs will develop late effects when treated with SRT for nasal tumors?
30 - 40%
344
What is the most common lung tumor in dogs?
Bronchoalveolar carcinoma (85%)
345
What is the most common lung tumor in cats?
Adenocarcinoma (60 - 70%)
346
What % of canine pulmonary malignant tumors had evidence of local vascular or lymphatic invasion?
71%
347
What % of dogs with pulmonary tumors have tumors found in multiple lung lobes?
37.1%
348
What percentage of cats with primary lung tumors show GI signs on presentation
20%
349
What % of cats had evidence of pulmonary metastasis of primary pulmonary tumor on CT?
53%
350
Which of the following chemotherapy protocols has proven to have a greater than 50% reduction in gross pulmonary adenocarcinoma in dogs?
Vindesine + cisplatin
351
What is the complication rate for CT guided lung biopsy?
43% (pulmonary hemorrhage and pneumothorax)
352
Which mutation has been identified in p53 of canine OSA?
Missense mutation of exons 4 - 8 in 25 - 47%
353
Which antibiotic has been shown to reduce canine OSA cell viability in vitro?
Enrofloxacin- regardless of p53 mutational status or downstream activity.
354
What is the metastatic rate of OSA affecting the head (mandible, maxilla, and skull)
37%
355
What is the MST for rib OSA following rib resection with and without chemotherapy?
Rib resection alone = 3 months
| Rib resection + chemo = 8 months
356
What is the MST for OSA of the canine scapula treated with subtotal scapulectomy surgery and chemotherapy?
8.2 months (246 days) (DFI = 210 days)
357
What is the MST of OSA distal to the antebrachiocarpal or tarsocrural joints?
MST = 466 days = 15.5 months
358
What is the MST for vertebral OSA treated with surgery, RT and chemo?
4 months (8.7 mo. in another study)
Sx alone = 42 days
Sx + chemo = 82 days
Dixon et. al 2019 VCO
359
What is the MST for mammary gland OSA treated with surgery alone?
3 months. Most died of pulmonary metastasis (62.5%)
360
What gene mutation has been detected in BMD with histioctyic sarcoma?
PTPN11 (MAP Kinase pathway)--> 36.67%
361
In a study by Barrett et. al VRU 2014, what % of dogs with histiocytic sarcoma with pulmonary involvement had internal air bronchograms?
57% (12/21)
362
In a study by Barrett et. al VRU 2014, which lung lobes were most commonly affected by HS?
Right middle and left cranial
363
In a study by Marlowe et al 2018 VCO regarding primary pulmonary HS in dogs, how many were found incidentally?
25%
364
What are the 4 negative prognostic indicators with HS?
Anemia, thrombocytopenia, splenic involvement, hypoalbuminemia.
365
Which region of bone is most suitable for limb spare?
Distal radius and ulna
--> Because function following carpal arthrodesis is good
366
Which anatomical location for OSA is typically seen in young dogs (mean age 4.5 - 5.4 years)?
Rib
367
What type of fluid should be given for diuresis with cisplatin and why?
NaCL
Because in a low chloride environment such as urine, cisplatin undergoes aquation and attacks renal epithelium. Maximizing chloride content with NaCl will help reduce aquation and thereby prevent renal damage.
368
What is the mechanism of action of bisphosphonates?
Inhibits Farnesyl diphosphate (FPP) synthase. FPP prenylated proteins are required for osteoclast function and survival.
369
What is the MST for dogs with telangiectatic OSA (confirmed via IHC) undergoing surgery +/- chemotherapy?
7 months (213 days)
370
What percentage of telangiectactic osteosarcomas were reclassified to hemangiosarcoma after IHC with factor VIII-RA/vWF?
21%, typically from an original diagnosis of tOSA to a reclassified diagnosis of HSA (11%).
371
Which type of OSA carries the best prognosis?
Parosteal
372
Primary appendicular HSA primarily affects which bone?
Tibia
373
What disease is commonly associated with MCE in cats?
FeLV/FIV
374
What is the MST of cats with OSA treated with surgery alone?
24 - 44 months
Low metastatic rate (5 - 10%) so chemotherapy not recommended.
375
NF-kB is inactivated and sequestered in the cytoplasm by?
IkB
376
Nf-kB is made up of which 2 proteins?
RelA (p65) and p50
377
c-KIT exon 11 is located in which part of the chromosome?
Juxtamembrane domain
This domain is responsible for preventing the kinase from being activated- therefore with mutations in exon 11 of this domain such as internal tandem duplications seen with MCT, there is a loss of autoinhibitory activity of the juxtamembrane domain and the kinase becomes constitutively activated.
378
Which 2 markers are primarily used to identify T-Reg cells?
FoxP3 and CD25
T-Regs are an immunoregulatory subset of CD4+ T cells.
379
Which two cytokines are secreted by iTregs and responsible for most of their immunosuppressive action?
TGF-B and IL-10
380
Which cytokine can act as a tumor suppressor AND promoter?
TGF-B
381
Tyrosinase is an example of which type of Tumor Associated Antigen?
Differentiation antigen
382
HER-2/neu is an example of which type of Tumor Associated Antigen?
Overexpressed antigen
383
V600 BRAF mutation is an example of which type of Tumor Associated Antigen?
Mutation antigen
384
What is the overall diabetic remission rate in cats with pituitary tumors and uncontrolled diabetes mellitus when treated with SRT?
32%
385
Which clinicopathologic finding is common in cats with hepatobiliary tumors?
Azotemia
386
Which protein can be found in the serum of up to 75% of dogs with HCC and 55% of dogs with bile duct carcinoma?
alpha-Fetoprotein (Differentiation antigen)
However it has limited value in the diagnosis and treatment of canine HCC as serum levels are also increased in other types of liver tumor such as bile duct carcinoma and lymphoma, and nonneoplastic hepatic disease.
387
In a study of 19 dogs undergoing US guided FNA of an adrenal lesion, what % had side effects?
5% (1/19) = Ventricular Tachycardia consistent with Pheochromocytoma.
388
What is the most common clinical sign associated with Conn’s Syndrome in cats?
Muscle weakness secondary to hypokalemia
Aldosterone secreting adrenal tumor
389
What is the mortality rate for cats undergoing adrenalectomy for neoplasia?
20%
20/26 cats (77%) survived in one study, and 8/10 (80%) in another (Holt et. al JVIM 2014)
390
What was the most common intraoperative complication in a retrospective of 86 dogs undergoing adrenalectomy? Barrerra et. al 2013 JAVMA
Hypotension (62%) followed by blood loss requiring transfusion (26%)
On multivariate analysis of risk factors for short term survival, extensive invasion was the most important risk factor.
391
In a study of 52 dogs undergoing adrenalectomy for adrenal tumor, what factors were significantly associated with shorter survival time?
Major axis length >5cm
Metastasis
Vein thrombosis
392
In dogs undergoing VMAT SRT for adrenal tumors with vascular invasion, what was the MST?
1030 days (34 months = 2.8 years)
The endocrine profile normalised in 2/3 dogs with cortisol secreting tumors. Radio-toxicities were mild and self-limiting. All dogs experienced progressive shrinkage of the tumor (mean reduction 30%).
393
What % of dogs developed hypothyroidism following RT for thyroid carcinoma?
47%
Development of hypothyroidism was not associated with the radiation protocol used, and median time to diagnosis of hypothyroidism was 6 months.
394
Which activating missense mutation has been identified in dogs with thyroid carcinoma and has also been described in humans?
K-RAS
395
What is the sensitivity and specificity of CT for determining histopath invasion of thyroid CA?
```
Sensitivity = 70%
Specificity = 100%
```
396
What is the MST of dogs with bilateral thyroid tumor undergoing thyroidectomy?
38 months
397
What is the MST of dogs with sublingual ectopic thyroid carcinoma treated with various modalities (surgery and/or I-131)?
19 months (562 days)
Compared to other locations, these dogs were significantly younger (9 years) and less likely to have metastasis (15% vs. 30%)
398
Mineralization of the kidney occurs when the calcium x phosphorus product exceeds _____?
70
399
What % of dogs developed hypocalcemia following surgical excision of parathyroid carcinoma?
47%
400
What % of canine insulinoma metastasize?
50%
401
What is the reported metastatic rate of Gastrinoma?
85%
402
What disease is associated with Glucagonoma?
Necrolytic migratory erythema (NME)
403
Which treatment for insulinoma acts by inhibiting secretion of insulin?
Octreotide
404
Tumors of which organs are associated with Multiple Endocrine Neoplasia type 2 (MEN2)?
Medullary thyroid carcinoma
Pheochromocytoma (Adrenal medulla)
+/- Parathryoid tumor
405
Inhibin-alpha is a sensitive and specific marker for which female reproductive tumor?
Granulosa-theca cell tumor (GTCT).
Inhibin-a is a glycopeptide synthesized in gonadal cells of the ovaries, and inhibits pituitary secretion of follicle-stimulating hormone (FSH).
406
What is the most common ovarian tumor in cats?
Granulosa-theca cell tumor
407
What is the most common ovarian tumor in dogs?
Ovarian adenocarcinoma
408
Which breeds have been shown to overexpress BRCA1 mutations with mammary CA?
English Springer Spaniels, Shih Tzu
409
What are the risk factors for canine bladder cancer? List 5.
1) Older-generation flea control products and lawn chemicals
2) Obesity
3) Cyclophosphamide exposure
4) Female sex
5) Breed associated risk (Scottish Terrier)
410
In a study by Hanazono et. al, what was the expression of p63, B-catenin, and Ki67 in TCC compared to normal urinary bladdder and polypoid cystitis?
p63 - significantly lower in TCC
B-catenin - significantly lower in TCC
Ki67 - significantly higher in TCC
In TCC, low p63 expression was significantly related to the presence of vessel invasion, metastasis, as well as short survival time.
411
What is the MST for dogs undergoing partial cystectomy and daily piroxicam for urothelial carcinoma, with or without chemotherapy?
772 days (26 months, 2.1 years)
76% had local recurrence within the bladder
11% had abdominal wall mets (median 150d later)
412
In a study by Blackburn et. al, 2013 on urethral stent placement for canine iUC, what was the only variable significantly associated with extent of urinary incontinence?
Duration of stranguria before SEMS placement
413
In a study by Blackburn et. al, 2013 on urethral stent placement for canine iUC, what was the MST after SEMS placement?
78 days
Treatment with NSAIDs before and chemo after SEMS placement increased MST to 251 days.
64.3% developed incontinence (26% severe)
414
In a study by McMillan et. al 2012 on self expanding nitinol urethral stent placement for canine iUC in 19 dogs, what % of dogs developed incontinence?
39% (7/18, in 1 dog stent placement was unsuccessful)
MST = 78 days (same as the Blackburn study)
415
What % of iUC are positive for HER2?
56 - 61%
HER2 expression was not associated with any clinical factors.
416
In a study of dogs with presumed primary renal lymphoma, what was the MST?
```
12 days (47 days for those that responded to chemotherapy- 50% PR seen).
Erythrocytosis in 51%, Azotemia in 86%
```
417
What is the most common site of bone mets in dogs with iUC?
Lumbar vertebrae (47% of dogs with boney mets)
Charney et. al 2016 Vet Path
9 - 14% of dogs evaluated had bone mets.
418
What percentage of canine urothelial carcinomas exhibit a BRAF mutation (V595E)?
> 80% (Withrow)
| 75% on ddPCR, 83% of both iUC and PC in free catch urine, Mochizuki et. al 2015 Plos One
419
What percent of dogs with transitional cell carcinomas are reported to develop a urinary tract infection during chemotherapy?
55%, primarily staphylococcus and e.coli
420
What is the median PFI for dogs with TCC undergoing partial cystectomy +/- various nonsurgical treatments?
(Marvel et. al, 2017)
235 days
Overall MST = 348 days.
MST for dogs treated with Sx + Piroxicam (w/or without chemo = 772 days)
Prognostic factors significant for PFI were full thickness excision and frequency of piroxicam administration.
421
What percentage of dogs in DIC are diagnosed with underlying neoplasia?
40%
422
Which enzyme is inhibited by Zoledronate to produce it's anti osteoclast activity?
Farnesyl diphosphate synthase
423
What % of cats with thrombocytopenia will have a diagnosis of neoplasia?
20%, most commonly associated with lymphoma
424
Other than PTH-rp, what are mediators of hypercalcemia of malignancy?
IL-1B, TGF-B, receptor activator of nuclear factor kappa-B (RANKL), tumor associated prostaglandins (PGE1/2)
425
Which mutation has been associated with polycythemia vera in canine patients?
JAK2
| 5/6 dogs
426
Paraneoplastic eosinophilia is suspected to be a result of the overproduction of which cytokines?
IL-5, IL-13, IL-17, GM-CSF and eotaxins.
427
What tumor is associated with Hepatitis B Virus in humans?
HCC
428
Which protein associated with Papillomavirus targets p53 for degradation in the ubiquitin pathway?
E6
429
Which protein associated with Papillomavirus binds to and inhibits pRB?
E7
430
The pathogenesis of PNS fever is predominantly due to excessive production of which cytokines?
IL-1, IL-6, TNF-a and interferons
431
Which virus is associated with Burkitt's Lymphoma in humans?
Epstein-Barr Virus
Also associated with some types of Hodgkin Lymphoma, Gastric Carcinoma, and nasopharyngeal carcinoma.
432
DNA base damage due to endogenous oxidative processes or exogenous DNA damage (ionizing radiation) is repaired by?
Base excision repair pathway
433
Which species of animal has been linked to a viral (hepadnavirus) etiology of hepatocellular carcinoma?
Woodchuck
434
What is the name of the paraneoplastic syndrome in humans (primarily seen with lung tumors) similar to Myasthenia Gravis, but instead is a result of calcium-channel autoantibody formation causing poor calcium influx from the presynaptic neuromuscular junction?
Lambert-Eaton Syndrome
435
In humans, human herpes virus 8 (HHV-8) is associated with which vascular tumor of endothelial cells?
Kaposi Sarcoma
More common in HIV patients
436
Which cells are affected by HIV?
CD4+ T cells
437
Chronic tumor retroviruses do not contain viral oncogenes but transform infected cells through a mechanism known as ___________?
insertional mutagenesis
438
FIV/HIV is what type of virus?
Retrovirus- classified as a lentivirus
439
What % of intact female dogs present with more than one mammary tumor at diagnosis?
70%
440
What is the reported cytologic sensitivity and specificity for a malignant mammary tumor diagnosis?
```
Sensitivity = 88%
Specificity = 96%
```
441
What % of canine malignant mammary tumors have been found to be HER2 positive (according to Withrow 5th ed)
17 - 29% (using HercepTest scoring system used in human medicine)
Overexpression of HER2 seen in 20 - 25% of human BC patients.
442
Increases of which cytokine are related with an increased risk of death from canine mammary tumors?
IL-10
Estela et. al, 2016 VCO
443
What is Paget's disease?
Carcinoma with epidermal infiltration of the nipple in women. Paget-like disease exists in the dog as well.
The carcinoma is present within the mammary gland, and carcinoma cells, either as individual cells or small aggregates, are present within the epidermis of the nipple.
444
What 3 criteria make up the Elston and Ellis Mammary Tumor Grading for dogs?
1) Tubule formation (>75%, 10 - 15%, <10%)
2) Nuclear pleomorphism (mild, mod, marked)
3) MI (0 - 9, 10 - 19, >20)
Grade I = 3 - 5
Grade 2 = 6 - 7
Grade 3 = 8 - 9
(Withrow pg. 543)
445
What are the 3 factors that are most consistently reported to be associated with prognosis for canine mammary tumors?
1) Tumor size
2) Lymph node involvement
3) WHO stage
Withrow pg. 543
446
Which of the following features has the highest level of evidence to support the addition of chemotherapy for dogs with mammary carcinoma?
A) Lymph node metastasis
B) Size > 3cm/40 cc
C) Type of carcinoma (such as inflammatory carcinoma)
D) Evidence of distant metastasis
B) Size > 3cm/40 cc
Withrow pg. 547, tablet 27-5
447
What was the most common alteration seen on kidney biopsies of dogs with mammary carcinoma?
Focal glomerular mesangial matrix expansion seen in 60%
448
What are the 3 main risk factors for mammary tumors in dogs and cats?
1) Age
2) Breed
3) Hormonal influence
449
Which drug when given perioperatively, significantly prolonged the disease free survival and overall survival in bitches with grade 2 or 3 carcinomas compared to controls?
Desmopressin (DDAVP)
450
What % of cats with mammary tumors have more than one tumor at diagnosis?
60%
451
What Ki-67 index has been established as prognostic in feline mammary carcinoma?
> 14%
Significantly associated with large tumor size, poor differentiation, presence of necrosis, estrogen receptor-negative, HER2-negative, and shorter overall ST.
Ki-67 expression also strongly and positively correlated with both regional and distant metastasis.
452
What is the reported MST of feline mammary carcinoma treated with unilateral radical mastectomy and doxorubicin based chemotherapy?
1998 days (vs. 414d with chain mastectomy alone)
453
How does ovariohysterectomy decrease the risk of mammary tumor development in cats? Compare the decrease in risk when OHE is performed < 6 months, between 7-12 months, and between 13-24 months of age.
91%, 86%, 11%
454
What is the most common complication in dogs following hypophysectomy?
Diabetes insipidus (53%)
455
Which tumor in humans can be caused by loss of tumor suppressor gene von Hippel - Lindau (VHL)?
Renal cell carcinoma
Loss of the VHL protein leads to constitutive activation of HIF, as VHL, in the presence of oxygen, ubiquinates the alpha subunit of HIF, targeting it for degradation.
456
What is the most common B-RAF mutation in humans? What is the canine equivalent?
V600E substitution in the kinase activation loop (90%), the equivalent in dogs (eg. iUC) is V595E
457
What is the target of vemurafenib?
B-RAF
458
Which guanine nucleotide exchange factor (GEF) is important in the MAP kinase pathway and promotes GTP loading of RAS?
Son of Sevenless (SOS)
Works together with adaptor protein GRB2 at the ligand activated receptor on the cell membrane.
459
Which viral particle was involved in the discovery of p53?
SV40 viral T-antigen
460
Which protein binds to and induces ubiquitination of HIF-a?
Von-Hippel Lindau protein (VHL)
461
True or false: Insulinomas in ferrets rarely metastasize
True. Long term survival seen with surgical resection, though recurrence is relatively common.
462
What are the 2 most common tumors in Ferrets?
1) Pancreatic islet cell tumor (insulinoma)
| 2) Adrenal cortical carcinoma
463
What are the clinical signs of adrenal tumor in Ferrets?
1) Cutaneous- bilateral truncal alopecia and patchy hair loss
2) Behavioral- Return to intact sexual behavior such as mounting, urine marking, and aggression.
3) Reproductive- Vulvar swelling in up to 90% of neutered Jills. Prostatic cysts in males resulting in dysuria.
464
What is the recommended treatment for Ferrets with adrenal tumors?
Surgical excision- good prognosis regardless of location, histologic grade, or completeness of excision.
465
What % of ferret adrenal tumors are bilateral?
20%
466
What is the second most common adrenal tumor in Ferrets?
Leiomyosarcoma- estrogen receptors demonstrated on the smooth muscle cells ins everal of these tumors.
Adenocarcinoma is most frequent
467
What are the 3 most common US findings in ferrets with lymphoma?
1) Intra-abdominal lymphadenopathy (12/14)
2) Peritoneal effusion (11/14)
3) Splenomegaly (8/14)
Suran et. al 2013 VRU
468
Which lymph nodes should be avoided when sampling Ferrets with suspected lymphoma due to reactive change that can be indistinguishable from lymphoma?
Abdominal lymph nodes
Ferrets commonly have chronic GI inflammation.
469
What % of ferret MCT present with multiple tumors?
30%. Universally benign.
470
True or False: Vaccine associated sarcomas in Ferrets have similar aggressive behavior as feline VAS
False- generally low grade with a slow growth rate and low metastatic potential- they all respond well to wide surgical excision.
471
What % of dogs with TCC had diagnostic samples obtained by cystoscopy. Give an answer for both females and males.
```
Females = 96%
Males = 65%
```
472
What % of dogs undergoing cystotomy for TCC developed abdominal wall seeding?
10.2%
Median time to met = 121 post sx, MST = 57d
Higuchi et al, 2013
473
Is IDH a tumor suppressor or oncogene?
oncogene
474
What is the target of the monoclonal antibody cetuximab?
EGFR
475
How does MYC promote cell-cycle progression?
Downregulation of CDK inhibitors and upregulation of CYCLIN D1, CDK4, CDC25A, and E2F
476
Which tumor types are more common in cryptorchid testes?
Sertoli cell tumor and seminoma
Inguinal cryptorchid >> abdominal cryptorchid
477
What testicular tumor was found to occur as a result of carcinogen exposure in military working dogs?
Seminoma
478
Which breed has been reported to have a syndrome of Sertoli cell tumors occurring in cryptorchid male pseudohermaphrodites?
Miniature Schnauzer
479
A dog with a perianal adenoma and testicular mass is most likely to have which testicular tumor type?
Interstitial cell tumor (due to testosterone secretion)
480
What is the best test to confirm hyperestrogenism secondary to sertoli cell tumor?
Decreased testosterone/estradiol ratio
Correlates better with feminization due to sertoli cell tumor compared to absolute increase in estradiol alone.
481
How long does it take for signs of hyperestrogenism from sertoli cell tumor to resolve following castration? (assuming no metastasis present)
1 - 3 months
482
Which testicular tumor is considered extremely radioresponsive?
Seminoma
483
What % of dogs with prostatic carcinoma exhibit a BRAF mutation?
85% (75% of iUC)
Mochizuki et. al Plos One 2015
484
Which FeLV subgroup has the ability to produce mediastinal lymphoma by causing overexpression of c-myc gene by integrating itself ADJACENT to the gene?
The Rickard strain of FeLV (FeLV-R)
485
Which FeLV subgroup is associated with natural transmission?
A
486
What is considered the precursor to prostatic neoplasia?
Prostatic intraepithelial neoplasia
487
Which breeds may be at decreased risk of prostatic cancer?
American Cocker Spaniel, Miniature Poodle, and Dachshund
488
Which 3 molecular factors are associated with bone metastasis in dogs with prostatic neoplasia?
1) PTH-rp
2) TGF-B
3) Endothelin
PTH-rp and TGF-B stimulate each other in positive feedback loop.
489
Which breed is most frequently reported in an original study of high-low oral FSA?
Golden Retrievers (52%)
490
Which oral tumor is frequently identified on histopathology as intraepithelial nests of neoplastic cells?
Melanocytic tumors
When these cannot be detected, IHC sensitivity will be low. Biopsy from areas containing overlying and adjacent epithelium may incerase the ability to detect.
491
Which IHC markers identify tumors of muscle origin (myocyte markers)?
Actin, desmin
| Eg. Leiomyosarcoma, rhabdomyosarcoma
492
What are the recommended surgical margins for malignant oral tumors?
At least 1 cm of macroscopically normal soft tissue or bone surrounding the tumor, ideally 2-3cm if possible.
493
What is misonidazole?
Radiation sensitizer
494
What is the maximum RT dose that the canine liver can tolerate?
30 Gy
495
Recurrence rate for oral FSA following surgical resection alone?
54 - 57%
Martano et. al 2018 The Veterinary Journal
496
What was the MST and recurrence rate when oral FSA is treated with a combination of surgery and adjuvant megavoltage RT?
MST = 743 days
Recurrence rate = 24%
Frazier et al., 2012
497
What was the maximum tolerated dose of Doxorubicin when combined with Palladia (2.75mg/kg EOD) in a Phase I study?
25mg/m2 q21d
DLT = neutropenia
Pellin et. al 2016 VCO
498
What are 2 TKI that target EGF receptor in non-small cell lung cancer?
Erlotinib and gefitinib
499
Mutation in the juxtamembrane domain of _____ has been implicated in acute myeloid leukemia.
FLT3
500
Which RAS oncoprotein is most commonly mutated in cancer?
K-RAS
501
What is Rheb?
activator of mTOR1, inhibited by TSC1/2
502
Which modular interaction domain is associated with AKT and serves as a membrane anchoring site for PIP3?
PH (Pleckstrin Homology) domain
503
Which modular interaction domain is associated with GRB2 and PI3K subunit p85?
SH2
504
Which modular interaction domain is associated with SOS and modulates its interaction with GRB2?
SH3
505
What is the function of RNA polymerase II?
Catalyzes the transcription of genes, regulated by transcription factors.
506
How do cytokine receptors differ from RTK?
They do not contain intrinsic TK activity, but rather transmit intracellular signals through association with cytoplasmic TK's (eg. JAK).
507
What is the name of a JAK2 kinase inhibitor?
Ruxolitinib
508
Which human cancer is most notably linked to NOTCH activation?
T-cell ALL (more than 50% harbor a gain of function mutation within the NOTCH1 receptor)
509
What is GSI?
y-secretase inhibitor, which is involved in the NOTCH pathway.
Cleavage by y-secretase releases the cytoplasmic domain fragment of intracellular NOTCH (NIC) from the plasma membrane, allowing it to enter the nucleus and modulate the expression of target genes (HES and HEY)
510
IHC for GIST?
vimentin (+), CD117/KIT (+), DOG-1 (+) +/- CD34, a-SMA, desmin (-), S100 (-)
97% stain positive for both KIT and DOG1. DOG1 has improved sensitivity & specificity to that of KIT for differentiating GIST and leiomyosarcoma (one KIT negative GIST was positive for DOG1).
511
DNA damage due to DNA polymerase inserting an incorrect base or creating helical distortions by inserting or deleting bases in short oligonucleotide repeats (microsatellites) during replication is repaired by which DNA repair pathway?
Mismatch Repair
512
What is the name for helical distortions created by DNA polymerase by inserting or deleting bases in short oligonucleotide repeats (microsatellites) during replication?
Insertion-deletion loops
513
PARP is important for which DNA repair pathway?
Base excision repair--> recruits LIGIII and XRCCI to seal the nick in the DNA back bone.
514
DNA damage due to UV radiation causing CC --> TT transitions is repaired by which DNA repair pathway?
Nucleotide excision repair
Deficient in patients with XP
515
Xeroderma pigmentosum is due to a deficiency in which DNA repair pathway?
Nucleotide excision repair (NER)
516
What form of DNA repair mechanism employs DNA glycosylases?
Base excision repair
517
Which 2 proteins are thought to compete for binding to DSB and channel the repair of DSB into HR or NHEJ respectively?
```
HR = RAD52
NHEJ = KU70/80
```
518
Which proteins make up the MRN complex?
MRE11, RAD50, and NBS1.
The MRN complex is important for signaling pathways in response to DNA DSB. ATM protein is held inactive in the cell as a dimer until DNA damage leads to autophosphorylation of ATM monomers leading to its kinase activity, which is enhanced by the MRN complex.
519
Which 3 kinases can sense DNA DSB?
ATM, ATR, and DNA-PKcs
520
Which phases in the cell cycle have checkpoints?
G1 (G1 - S), S (Intra-S), and G2 (G2 - M)
521
What are the 2 general types of cell cycle check points?
1) Mitotic spindle assembly checkpoint
| 2) DNA integrity checkpoints
522
MAD2, BUBR1, BUB1, and BUB3 proteins are critical constituents of the __________ pathway.
Spindle-checkpoint pathway
523
What is the term used to describe an effect of radiation in which the probability of occurrence is a function of dose, with no threshold?
Stochastic
Eg. Cancer, hereditary effects
524
What is the term used to describe an effect of radiation in which the severity of the effect depends on the dose above a threshold?
Deterministic
Eg. Sterility, acute side effects, mental retardation (in utero), cataracts.
525
Southern blot is used to analyze what? Options are:
1) Gene expression
2) Characterize protein
3) DNA sequence/structure
3) DNA sequence/structure
526
Northern blot is used to analyze what? Options are:
1) Gene expression
2) Characterize protein
3) DNA sequence/structure
1) Gene expression
527
Western blot is used to analyze what? Options are:
1) Gene expression
2) Characterize protein
3) DNA sequence/structure
2) Characterize protein
528
Does IHC best evaluate cell surface or cytoplasmic proteins?
Cytoplasmic
This is b/c formalin fixation damages cell surface proteins
--> Flow cytometry better evalutes cell surface proteins.
529
In a study by Comazzi et. al 2011 JVIM what was the MST for dogs with CD3+ CD8+ T-CLL?
930 days = 31 months = 2.6 years
Anemic dogs with T-CLL survived significantly shorter time than dogs without anemia.
530
In a study by Comazzi et. al 2011 JVIM what was the MST for dogs with CD21+ B-CLL?
480 days = 16 months = 1.3 years
Old dogs with B-CLL survived significantly longer than did young dogs < 8 yo).
531
In a study by Comazzi et. al 2011 JVIM what was the MST for dogs with atypical CLL (CD3- CD8+, CD3+ CD4- CD8-, CD3+ CD4+ CD8+, and CD3+ CD21+)?
22 days
532
What are the 4 main characteristics of English Bulldogs presenting with B-CLL?
Younger age at diagnosis
55% hyperglobulinemic
More likely to have lower MHC II and CD25 expression
*New 2020 study suggesting this is actually non neoplastic Polyclonal B-cell lymphocytosis
533
What size biopsy can be collected with Needle Core Biopsy?
1mm x 10 - 15mm
534
True or false: Tumor tissue itself is very poorly innervated and does not require local anesthesia prior to biopsy.
True, it is the skin/SQ around the tumor that you may use local anesthesia for.
535
What are 3 examples where excisional biopsy would be appropriate?
1) "Benign" skin tumor
2) Splenic mass
3) Testicular tumor
Also amputation for OSA
536
When biopsies are performed on the leg or tail, the incision should be _________ and not _________.
Logitudinal and NOT transverse.
537
Methyldiazonium ion and 5-aminoimidazole are the active metabolites of which chemotherapy drug?
Dacarbazine
538
Which group of drugs act during the S phase of the cell cycle?
Antimetabolites
539
Induction of glutathione S-transferases by tumor cells is a mechanism of acquired resistance to which chemotherapy drugs?
Nitrogen mustards
Increases intracellular glutathione
540
Which drug competitively inhibits the enzyme dihydrofolate reductase (DHFR)?
Methotrexate
541
Patients with a deficiency in which enzyme will be more sensitive to the side effects of 5-fluorouracil?
Dihydropyrimidine dehydrogenase
542
Which drug causes DNA double-strand breaks by making a complex with ferrous iron before binding DNA?
Bleomycin
543
What are the 2 main toxicities associated with EGFR inhibition?
1) Diarrhea
| 2) Skin toxicities
544
Which drugs cellular uptake may be reduced by the presence of amino acid leucine?
Melphalan
545
Which drug can reverse resistance as a result of P-glycoprotein in cell culture?
Cyclosporine (also verapamil)
But often drugs still resistant because of MRP1.
546
Name an example of a drug that will have a decreased ability to cross the plasma membrane under acidic extracellular conditions?
Doxorubicin (weak base) --> becomes protonated under acidic conditions, decreasing ability to cross plasma membrane.
547
Name an example of a drug that will have an increased ability to cross the plasma membrane under acidic extracellular conditions?
Chlorambucil and Melphalan (weak acids)
548
What is the target of Alemtuzumab?
CD52 (T-CLL)
549
What are the 3 main benefits of Liposomal or Nanoparticle drug delivery?
1) Slow continuous release
2) Fusion of liposomes with cell membranes
3) Selective deposition of nanoparticles in tumor tissue
550
What is Trastuzumab emtansine (TDM1)?
anti-HER2 monoclonal antibody bound to the microtubule-disrupting agent DM1 approved for women with HER2 positive metastatic BC
551
Which protein is mutated/lost in SCID mice to make them immunodeficient?
DNA-PKcs--> NHEJ repair pathway protein.
Inability to process and rejoin the broken DNA molecules produced endogenously during rearrangement of immunoglobulins and T-cell receptor loci.
552
What are the 2 major protein complexes implicated in the NHEJ pathway?
1) DNA-dependent protein kinase (DNA-PK) complex
| 2) XRCC4/ligase IV complex
553
How many tumor cells necessary for 1g (1cm) of tumor (smallest clinically detectable mass)?
1 x 10^9
554
Which antineoplastic drugs can potentially cause pulmonary fibrosis?
Tanovea, Hydroxyurea, CCNU (cats), bleomycin, Mitomycin C
555
How does irinotecan produce diarrhea?
Direct cholinergic effect on the cells of the intestinal mucosa. Can be prevented through the use of anticholinergic drugs (atropine).
Second type of diarrhea, secretory in nature, may occur several days following administration and may be a result of damage to the mucosa coupled with cytokine release.
556
What is a potential unique side effect of Doxil in dogs? What is a potential treatment to reduce severity of this side effect?
Plantar-palmar dysesthesia (PPES).
| Treatment = Pyridoxine (Vitamin B6)
557
In a study of 216 BMD, which factor was associated with a significantly higher and lower risk of developing HS respectively? (Ruple et. al 2016)
Higher risk = Orthopedic conditions (OR = 2.5)
| Lower risk = Receiving anti-inflammatory medications (prednisone, carprofen, meloxicam) (OR = 0.42)
558
What does a combination index of >1 represent when assessing the combination of 2 chemotherapeutic drugs?
Synergy
559
What does a combination index of <1 represent when assessing the combination of 2 chemotherapeutic drugs?
Antagonism
560
What does a combination index of = 1 represent when assessing the combination of 2 chemotherapeutic drugs?
Additivity
561
What is the mechanism of action of Dexrazoxane?
Chelates iron
Because complexes between iron and anthracyclines such as doxorubicin (free radical formation) appear to mediate cardiac toxicity, chelating free iron decreases cardiac toxicity.
Dose = 10x the dose of doxorubicin given.
562
What are 2 drugs that could increase the antitumor activity of doxorubicin by inhibiting multidrug resistance?
1) Verapamil
| 2) Cyclosporine
563
Define sublethal damage
Damage that can be repaired (eg. by DNA repair mechanisms like BER).
564
Patients with a deficiency in which enzyme will be more sensitive to the side effects of 5-flurouracil?
Dihydropyrimidine dehydrogenase
565
The study of the relationship between drug effect and it’s concentration is known as?
Pharmacodynamics
566
The study of the time course of drug and metabolite levels in different body fluids and tissues, including absorption, distribution, metabolism, and elimination is known as?
Pharmacokinetics
567
The amount of drug that is available after oral administration compared to that after IV administration is referred to as?
Bioavailability
568
The study of how genetic features of the patient (and their tumor) will influence response and toxicity is referred to as?
Pharmacogenetics
569
Which chemotherapy group has been most commonly implicated as the cause of secondary malignancy?
Alkylating agents
Mostly AML
570
What is the most common site of alkylation of DNA by nitrogen mustards?
N7 position of guanine
571
What is the primary interaction between Cisplatin and DNA?
Binding to the 7 positions of the guanine and adenine bases, causing 95% INTRASTRAND crosslinks primarily between adjacent guanine bases or adjacent guanine and adenine sites. (Adducts)
572
Which part of the kidney is most sensitive to cisplatin?
Pars recta of proximal tubule
573
In a study by Selmic et. al 2014 comparing 5 different combination carbo vs. Dox protocols, which protocol resulted in the fewest AE? Options are: 1) CARBO 4, 2) CARBO 6, 3) DOX q 14d x 5, 4) DOX q21d x 5, 5) Alternating carbo/Dox q21d x 3
2) CARBO 6 had lowest proportion of dogs experiencing AE.
No difference in risk of development of metastases or death between groups.
574
In a study by Skorupski et. al 2013 comparing dogs with osteosarcoma receiving carbo alternating dox vs. single agent carbo, what was the DFI in dogs receiving carbo alone?
DFI - 425 days, significantly longer than dogs receiving alternating carbo and dox (135 days)
Toxicity similar between groups. Suggests 6 dose of carbo may be associated with superior DFI compared to 6 total doses of Carbo and Dox.
575
In a study by Woodruff et. al 2019 in dogs with intranasal tumors receiving alternating carbo and dox in conjunction with oral piroxicam, what was the overall MST?
234 days
Sarcomas had the longest MST with 448 days. Adenocarcinoma = 280 days
TCC = 163 days
SCC/anaplastic CA/undifferentiated CA = 59 days
576
In a study by Dank et. al 2012 VCO on dogs with oral melanoma treated with surgery followed by adjuvant carboplatin (+/- RT), what was the overall MST?
MST = 440 days
The overall median PFS = 259 days
First prorgression free survival event = local recurrence in 41%, mets in 41%.
577
In a study by Gillem et. al VCO on dogs with relapse lymphoma treated with carbo +/- cytarabine, what was the RR for the combo of carbo + cytarabine?
Carbo + cytarabine RR = 28.6%
MTTP responders = 56d
MST responders = 109d
578
In a study of cats with colonic adenocarcinoma treated with subtotal colectomy and adjuvant carboplatin, what was the MST? (Aretaga et al JAAHA 2012)
MST = 269 days
Median DFI = 251 days
+ prognostic factor for DFI = weight loss as a presenting sign
- prognostic factors for MST = nodal and distant metastasis
579
In a study by Fidel et. al JVIM 2011 on cats with oral SCC treated with accelerated RT + Carbo, what was the MST?
MST = 163 days
Significant predictors of survival = site (tonsil or cheek responded better with mean ST of 724 days, median not reached) and whether there was a CR at 30 days.
580
In a phase I study of oral Satraplatin in dogs, what was the MTD?
Selting et. al JVIM 2011
35mg/m2/d for 5d q3-4 weeks.
In the 6 dogs receiving in the adjuvant setting for OSA, DFI = 456d, MST = 659d
Platelets consistently reached nadir sooner than did neutrophils (day 14 vs. 19)
581
Which platinum agent is reported to cause ototoxicity?
Cisplatin
582
Which chemotherapy drugs activity is increased with addition of leucovorin?
5-FU, because inhibition of TS by FdUMP is dependent on a folate cofactor.
583
Which chemotherapy drug toxicity can be rescued by addition of leucovorin?
Methorexate, because methotrexate blocks the formation of reduced folate by inhibiting dihydrofolate reductase, administering reduced folate circumvents the effects of methotrexate by providing products of the interrupted metabolism (same with administration of thymine and exogenous purines)
584
Which antimetabolites require triple phosphorylation for activation?
1) 5-FU (uracil analog)
2) Cytosine arabinoside (cytosine analog)
3) Gemcitabine (cytosine analog)
585
Which 2 chemotherapeutics are known for their potential increased toxicity with specific genetic mutations leading to decreased metabolic deactivation of the drug?
5-FU--> Dihydropyrimidine dehydrogenase (DPD)
| Irinotecan--> UGT1A1 gene (increased levels of SN-38)
586
Which drugs may cause Palmar Plantar Erythrodysesthesia? (Hand-foot syndrome)
```
Pegylated Doxorubicin (Doxil)
Capecitabine
5-FU
Sunitinib
Sorafenib
```
587
Which receptors does Palladia inhibit?
Split kinases--> VEGFR, PDGFR, c-KIT and FLT-3
588
Which 2 chemotherapy drugs are associated with resistance due to inactivation by binding to sulfhydryls (glutathione or metallothionien)
1) Alkylating agents
2) Cisplatin
Tannock pg. 453 Table 19-1
589
Elevated production of Dihydrofolate Reductase (DHFR) would lead to resistance to which chemotherapy drug?
Methotrexate
590
Mutation of thymidylate synthase that leads retained function but decreased affinity for chemotherapy binding/inhibition would lead to resistance to which chemotherapy drug?
5-FU, premetrexed, MTX
591
Gene amplification of Dihydrofolate Reductase (DHFR) gene would lead to resistance to which chemotherapy drug?
Methotrexate
592
Downregulation and production of mutant forms of topoisomerase I would lead to resistance to which chemotherapy drugs?
Camptothecin
| Irinotecan
593
Mutations of the topoisomerase II ATP binding site or around the catalytic tyrosine residue in the DNA-binding region of topoisomerase II (reduced topoisomerase II) would lead to resistance to which chemotherapy drugs?
Etoposide
Doxorubicin
Mitoxantrone
594
Defective NER would lead to increased sensitivity to which chemotherapy agent?
Cisplatin
595
Point mutation of p210 BCR-ABL protein in CML or increased copy number (amplification) of the BCR-ABL fusion gene may lead to resistance to which anti-neoplastic agent?
Imatinib
596
What is the action of Bortezomib?
Proteosome inhibitor--> improved prognosis in patients with MM by inhibiting cell-adhesion mediated drug resistance.
597
Name 2 markers of apoptosis?
1) Activated caspase-3
2) Increase in TUNEL positive cells
Also DNA ladder formation, Annexin V labeling, and DAPI
598
Name a drug that localizes to hypoxic cells?
Pimonidazole
599
Necroptosis is dependent on which proteins?
RIP1 and RIP3 kinase
Necroptosis = programmed form of necrotic cell death, usually mediated by TNF-alpha activation of TNFR1.
Active CASP8 normally cleaves RIP1/3 and activates executioner caspases. If CASP8 deficient or death receptor not activated, RIP1/RIP3 available to trigger necroptosis.
600
Which drug may be more active against tumor stem cells?
Salinomycin
Tannock pg. 463
601
In the first study of dogs (O'Brien 1993) with OSA treated with pulmonary metastasectomy, what was the MST (overall and following pulmonary metastasectomy?)
Overall = 487 days
| After sx = 176 days
602
In the original study of pulmonary metastasectomy for dogs with OSA, what were the criteria established?
1) Primary tumor in complete remission, preferably for >300 days
2) 1 or 2 nodules visible on plain CXR
3) Cancer only found in the lung (negative bone scan)
4) Long doubling time (>30 days) with no new visible lesions.
603
In a recent study of dogs treated with stage III OSA following treatment with amputation and chemo, with or without metastasectomy, what was the difference in MST between the two groups following diagnosis of stage III OSA? (Turner et. al 2017 JAVMA)
With metastasectomy = 230 days
No metastasectomy = 49 days
Survival advantage identified for dogs with <3 nodules and DFI >275 days that actually received pulmonary metastasectomy.
604
Thamm et. al (2012, Journal of Cellular Biochemistry) showed that pre-treatment of canine and human osteosarcoma cells with valproic acid (HDAC inhibitor) resulted in sensitization to which chemotherapy drug?
Doxorubicin
Partially by increasing nuclear doxorubicin accumulation, or inhibition of the cellular ability to repair DNA damage.
605
What are the three main criteria for combining chemotherapy drugs?
1) Non-overlapping dose-limiting toxicities
2) Different mechanisms of action
3) Known single agent activity against the tumor
A 4th one is the drugs should be used at optimal dose and schedule (maximal dose intensity) and drug combinations should be given at consistent intervals.
606
What is the day-worst drug rule?
If 2 non-cross-resistant drugs are used intermittently in treatment, then the drug with the weaker killing rate has to be applied first and/or for a longer period of time.
607
What is the active metabolite of DTIC and TMZ?
Methyltriazenoimidazole carboxamine (MTIC)
DTIC activated in the liver (via cytochrome P450), TMZ activated spontaneously.
608
What was the RR and MST for dogs with Advanced Stage HSA treated with DAV? (Dervisis et. al 2011 JAAHA)
```
RR = 47.4%
MST = 125 days, TTP = 110d
```
Dacarbazine dose reduction positively affected TTP and MST. Age negatively affected TTP.
609
What was the ORR for DTIC as a rescue agent for histiocytic sarcoma? Kezer et. al 2017 VCO
17.6% (3 PR)
Median event free survival for dogs that experienced objective response = 70 days.
610
What are 3 mechanisms of resistance to TMZ?
1) High levels of AGT or MGMT
2) Increased BER
3) Defects in MMR
611
In a study comparing TMZ to TMZ/DOX combination for relapse lymphoma, what was the main finding?
Treggiari et. al 2017 VCO
No difference in MST and TTP between groups.
Overall MST 40 days (TMZ = 40 days, TMZ/DOX = 24 days)
Fewer toxicities in TMZ only group.
612
In a study comparing RT alone vs. RT + TMZ for oral MM with gross disease, what was the difference between TTP?
Median TTP was significantly longer in RT + TMZ group (205 days) compared to RT alone (110 days).
RR & ST not significantly different between groups and both treatments well tolerated.
613
What was the MST of RT alone vs. RT + TMZ for canine glioma?
RT alone = 383 days
RT + TMZ = 420 days
*Not significantly different (p = 0.61)
Positive correlation with survival for ratio between target and brain volume <5% and normal mentation.
614
Cellular uptake of streptozotocin is dependent on which transporter?
GLUT2
615
What was the most common side effect in a prospective study of biweekly Streptozotocin in 19 dogs with insulinoma?
Diabetes mellitus (42%)
616
What was the PFS and MST in a prospective study of biweekly Streptozotocin in 19 dogs with insulinoma treated following surgery (most b/c of metastasis or recurrence of hypoglycemia)?
Northrup 2013 JVIM
```
PFS = 195 days
MST = 308 days
```
617
In a recent study of dogs with insulinoma, what was the MST following surgery and subsequently receiving prednisolone therapy on relapse?
MST = 1316 days
| 785 days for dogs undergoing surgery, overall MST = 550 days
618
In a study of clinico-pathological criteria as prognostic indicators in canine insulinoma (Buishand et. al 2010 The Veterinary Journal), which factor was prognostically significant for both the DFI and OST on multivariate analysis)?
Ki67 index
619
What was the ORR to the MOMP protocol for relapsed lymphoma and median duration of response? (Back et. al VCO 2013)
ORR = 51.1% for a median of 56 days
MOMP = Mechlorethamine, vincristine, melphalan, prednisone
620
In a large retrospective study of dogs receiving CCNU for a variety of tumor types, what % of dogs had elevated ALT? What was the incidence of hepatic failure? (Heading et. al Aust Vet 2011)
Elevated ALT = 48%
Hepatic failure = 1.2%
Potential renal toxicity in 12%
621
In a prospective randomized clinical trial assessing the efficacy of Denamarin for prevention of CCNU-induced hepatopathy, what were the 3 primary findings?
1) CCNU alone group had significantly greater increase in ALT, AST, ALP and bilirubin.
2) CCNU alone group had significantly greater decrease in serum cholesterol
3) CCNU alone group significantly more likely to have treatment delayed or d/c because of increased ALT
*Liver enzymes still increased in 68% of cases CCNU + denamarin
622
What are the features of thymoma on cytology?
Neoplastic epithelial cells interspersed between large numbers of small lymphocytes (and occasional mast cells).
Nondiagnostic samples common due to either small % of epithelial cells, the presence of only small lymphocytes, or the presence of cyst within the mass.
623
What are Hassall's corpuscles?
Cytoplasmic structures present in thymocytes, not usually visualized in Wright-Giemsa preparations in comparison to H&E.
Withrow pg. 689
624
How do you differentiate thymoma from lymphoma on flow cytometry?
Simultaneous expresion of CD4 and CD8.
Thymoma --> At least 10% lymphocytes co express CD4/CD8
Lymphoma --> <2% lymphocytes co express CD4/CD8.
625
What are the positive prognostic factors for Thymoma in dogs? Name 3.
1) Surgically resectable
2) Lack of ME or aspiration pneumonia
3) Significant lymphocytic infiltrate
In cats--> cystic thymomas better prognosis
Withrow pg. 690
626
In a study of CCNU in cats (Musser et. al JFMS 2012), what % of cats had increased ALT activity above reference interval 1 month after starting treatment?
6.8%
1 cat developed clinical signs potentially associated with hepatotoxicity without a concurrent increase in ALT. Clinically significant hepatic injury is seemingly uncommon in cats treated with CCNU.
627
Which drugs when administered concurrently with doxorubicin may increase cardiotoxicity?
Paclitaxel and Trastuzumab
628
In a pharmacokinetic modeling study of doxorubicin in ABCB1 null mutants (Gustafson and Thamm JVIM 2010) what were the estimated dosages for serum and gut to approximate exposure in ABCB1 wild type population at dose of 30mg/m2?
```
Serum = 25mg/m2
Gut = 10.7mg/m2
```
Dosage reductions necessary to prevent GI toxicosis likely result in subtherapeutic concentrations, thereby reducing DOX efficacy in ABCB1(null) dogs
629
In a study of dogs receiving 2nd CHOP following relapse of multicentric lymphoma (Flory et. al 2011) what % of dogs achieved a CR following re-treatment?
78% with a median second remission duration of 159 days.
Median time off chemo = 140 days for dogs that achieved CR after retreatment vs. 84 days for dogs that failed to respond to treatment.
Median second remission duration for dogs with initial remission duration >289 days = 215 days, vs. 100 days for dogs whose initial remission duration was <289 days.
630
What was the RR and median response duration for dogs receiving doxorubicin for non-resectable SQ HSA? (Wiley et. al, VCO 2010)
RR = 38.8% (1 CR)
Median response duration = 53 days
4 dogs had complete surgical excision after chemo
MPFI complete surgical excision after neoadjuvant chemotherapy significantly longer (207 days versus 83 days)
631
What was the MST for cats undergoing surgical resection of discrete high grade GI lymphoma followed by CHOP chemotherapy? (Gouldin et. al, VCO 2017)
MST = 417 days (DFI = 357 days)
| Most cats were stage I or stage II (95%), only clinical stage had a significant effect on both MST and DIF.
632
What was the median DFI and MST for cats with mammary adenocarcinoma treated with radical mastectomy followed by mitoxantrone?
```
DFI = 360 days
MST = 480 days
```
633
What 4 drugs make up DMAC protocol?
```
D = Dexamethasone
M = Melphalan
A = Actinomycin D
C = Cytosar
```
634
Which vinca alkaloid can be given PO?
Vinorelbine
635
What is the drug interaction between L-spar and Vincristine?
L-spar reduces hepatic clearance of vincristine
636
Which chemotherapy drugs can potentially cause SIADH? (hyponatremia)
- Cyclophosphamide
- Cisplatin
- Vinca alkaloids
637
What is the MTD of vinorelbine in cats?
11.5mg/m2
DLT = neutropenia, vomiting, and nephrotoxicity
638
Capecitabine is a prodrug of which antimetabolite?
5-FU
639
Which kinase is the rate limiting step of Cytarabine phosphorylation? Options are 1) CdR kinase, 2) dCMP kinase, 3) NDP kinase
CdR kinase--> mutation of this kinase can lead to ara-C resistant cells.
640
What are the mechanisms of resistance to ara-C?
1) Overexpression of antiapoptic protein Bcl-2 and Bcl-XL
| 2) Mutation of CdR kinase--> rate limiting step of ara-C phosphorylation
641
What was the outcome of a 2017 study (Gillem et al. VCO) on the efficacy and toxicity of carboplatin and cytarabine chemo for dogs with relapsed or refractory lymphoma?
1) RR = 28.6% for the combination
2) Although some dogs responded to the combination, toxicity was high (neutropenia 52.6% and thrombocytopenia 84%) and the responses were not durable (TTP = 18 days).
642
What was the response rate for relapse/refractory lymphoma to bleomycin and cytosar? (Batschinski et. al JAAHA 2018)
```
ORR = 36.8%
TTP = 15 days
```
643
What was the RR and MST following initiation of DMAC as a rescue for feline lymphoma?
(Elliott, VCO 2018)
```
RR = 26%
MST = 17 days
```
Most cats tolerated the protocol well.
644
Why are Gemcitabine and Carboplatin synergistic?
Increased propensity of platinum-DNA adduct formation after GEM triphosphate incorporation into the growing DNA strand
--> GEM can inhibit DNA repair of platinum adducts and crosslinks
645
What are the mechanisms of resistance to Gemcitabine?
1) Decreased tumor levels of CdR kinase
2) Induction of cytidine deaminase
3) High concentration of HSP
4) Increased expression of RR
5) Inhibition of nucleoside transporters (hENTs +/- hCNT)
646
Which test is most commonly used to measure/quantify plasma levels of chemotherapy agents and their metabolites?
High performance liquid chromatography (HPLC)
647
In a study on gemcitabine for incompletely excised HCC what was the MST? (Elpiner et al. VCO 2011)
MST = 983 days (massive 1339d, nodular 983d, diffuse 113d)
Nonresectable = 197d
Did not seem to extend survival for diffuse or compared to sx alone for massive, though nodular had an unexpectedly long survival.
648
In a study of 34 cats with exocrine pancreatic carcinoma, what were the 3 negative prognostic factors found? (Linderman et. al 2013 VCO)
1) Lack of treatment (sx or chemo), 165d vs. 7 days
2) Abdominal effusion (MST = 30 days)
3) NSAID (MST = 26d)
Overall MST = 97d
649
In a study by Burton et. al 2011 JVIM on metronomic cyclophosphamide comparing 12.5mg/m2/d to 15mg/m2/d, what was the major conclusion?
Dogs that received 15mg/m2/d showed decreases in both the number and % of Tregs as well as the tumor MVD compared to 12.5mg/m2/d which only showed significant decrease in the # of Tregs.
650
For dogs with digit melanoma treated with loco-regional control & receiving the melanoma vaccine, what was the MST?
MST = 476 days
| 105d with mets, 533 days without mets
1 yr survival of 63%. 48% of dogs without mets alive @ 3 yrs
651
Name 2 Veterinary examples of autocrine loops leading to RTK dysregulation.
1) OSA--> co-expression of MET and HGF
| 2) HSA--> co-expression of KIT and SCF
652
In dogs receiving imatinib, what specific toxicity can be seen in this species?
Hepatotoxicity
653
In a study evaluating hypertension and proteinuria development in dogs receiving Palladia (Tjostheim et. al 2016 JAVIM) what % of dogs developed SBP > 160mmHg?
37%
Systolic BP was significantly higher in previously normotensive treatment dogs after initiation of treatment with Palladia compared to baseline.
654
What was the MTD of CCNU when combined with Palladia 2.75mg/kg PO EOD? (Pan VCO 2016)
50mg/m2 q 3 weeks
DLT = Neutropenia
655
What was the MTD of Carboplatin when combined with Palladia 2.75mg/kg PO EOD? (Wouda et. al VCO 2018)
200mg/m2 IV q 3 weeks
DLT = Neutropenia
656
What was the MTD of Doxorubicin when combined with Palladia 2.75mg/kg PO EOD? (Pellin et. al VCO 2016)
25mg/m2 IV q 3 weeks
DLT = Neutropenia
657
What was the MTD of Vinblastine when combined with Palladia 3.25mg/kg PO EOD? (Robat et. al VCO 2012)
1.6mg/m2 q 2 weeks
DLT = Neutropenia
658
In a phase 1 study of combination Palladia and piroxicam, what was the primary finding?
No MTD or DLT found after 5 dose escalating cohorts therefore the combination of both standard dosages is judged safe (3.25mg/kg PO EOD Palladia, 0.3mg/kg PO daily Piroxicam)
659
In the original placebo-controlled study of Palladia for the treatment of dogs with recurrent mast cell tumor following surgical excision (London et. al 2009 Cancer Therapy), what was the ORR?
ORR = 42.8%
Additional 16 dogs = SD for overall clinical benefit of 60%
Median objective response duration = 12 weeks
Median TTP = 18.1 weeks
660
In a study of pulse administered Palladia (days 1, 3 & 5 of 21 day cycle) + Lomustine (50mg/m2 q21d) for canine MCT, what was the ORR and PFS? (Burton et. al JVIM 2015)
```
ORR = 46%
PFS = 53 days
```
661
In a study of palliative RT, Palladia, and Pred for Canine MCT, what was the median PFI?
PFI = 316 days
ORR = 76.4% (58.8% CR)
Median time to best response = 1 month
662
What was the ORR for dogs receiving Palladia for iUC? (Gustafson et. al JAAHA 2019)
6.7%
SD = 80%, TTP = 96d, MST = 149d
663
What was the MST for dogs with stage 4 AGASACA receiving Palladia?
MST = 356 days (PFI = 354d)
| No CR or PR, 13/15 (87%) had clinical benefit
664
In a study of the use of melphalan in dogs with AGASACA, what was the MST of dogs with lymph node metastasis undergoing cytoreduction of local disease and lymph node removal followed by melphalan chemotherapy?
20 months (29.3 months without mets)
665
In dogs with chemodectoma treated with Palladia, what % of dogs with clinical signs had improvement or complete resolution?
Improvement = 90%
Complete resolution = 81%
MST = 823 days, ORR = 10%
666
ALP and ALT are more commonly increased in:
A) Primary hepatic tumors
B) Metastatic liver tumors
A) Primary hepatic tumors
667
AST and bilirubin are more commonly increased in :
A) Primary hepatic tumors
B) Metastatic liver tumors
B) Metastatic liver tumors
668
AST-to-ALT ratio < 1 is consistent with which hepatic tumor types?
HCC
| Bile duct carcinoma
669
AST-to-ALT ratio > 1 is consistent with which hepatic tumor types?
Neuroendocrine tumor
| Sarcoma
670
In a study of Palladia toxicity in cats (Merrick et. al VCO 2017) what % of cats developed ALT elevations?
7.2%
Azotemia in 14.5%
GI tox in 21.8% (lower than previously reported for dogs)
671
What was the response rate for cats with FISS treated with Palladia? Holtermann et al. VCO 2017
0% --> No clinical response measurable.
672
What is the sensitivity of BRAF-Plus to detect CNA in the urine of patients with iUC?
(Mochizuki Vet Path 2016)
67%
100% sens and spec in tissue samples.
673
Increases in levels of the excision repair cross complementation group (ERCC1) enzyme which plays a rate limiting role in the NER pathway, would lead to resistance to which chemotherapy drug?
Cisplatin
Cisplatin induces cell death by forming DNA-platinum adducts and interstrand DNA crosslinks but resistance can ensue if the lesions are repaired. Repair of platinum-modified DNA often involves NER.
Tannock Pg. 454
674
Platinum drug induced DNA adducts and interstrand DNA crosslinks are primarily repaired by what DNA repair pathway?
NER
675
Increases in GSH peroxidase would lead to resistance to which chemotherapeutics?
Doxorubicin, etoposide
676
Increases in GSH S-transferase (GST) would lead to resistance to which chemotherapeutics?
Cisplatin and alkylating agents
677
Decreases in UMP kinase would lead to resistance to which chemotherapeutic drug?
5-FU
678
Decreased deoxycytidine kinase or increased deoxycytidine deaminase would lead to resistance to which chemotherapeutic drugs?
Cytarabine and Gemcitabine
679
Decreased polyglutamation would lead to resistance to which chemotherapeutic drug?
Methotrexate
680
What was the ORR and Median PFI for dogs receiving alternating Tanovea and Dox for naive multicentric lymphoma?
ORR = 84% (CR = 68%)
| Median PFI = 194 days
681
What was the RR for combined 5-FU and carboplatin for the treatment of canine carcinoma? (Menard et. al VCO 2017)
43%
One dog had an episode of ataxia, which could not be differentiated between otitis and 5-FU neurotoxicity.
682
In a study of Tanovea for dogs with relapse lymphoma, what was the ORR? What was the conclusion regarding dosing 1.0mg/kg vs. 0.82mg/kg?
ORR = 74% (45% CR)
Response rate and PFI similar between groups. Both treatment groups similarly well tolerated.
683
What are 2 unique side effects of Tanovea?
1) Dermatologic
| 2) Pulmonary fibrosis
684
Which protein was found to play a role in intracellular activation of Tanovea, and mutations in this protein led to resistance?
Adenosine Deaminase-like (ADAL) protein
Frey et. al Anticancer Research 2013
685
What was the ORR for dogs with cutaneous lymphoma treated with Tanovea?
(Morges et. al 2014 JAVIM)
45% (1CR, 4PR)
686
Which virus is the most popular viral delivery mechanism?
Adenoviruses
687
PTEN mutations have been identified in which canine cancers?
Osteosarcoma
Melanoma
Hemangiosarcoma
Mammary carcinoma
688
Masitinib targets which three tyrosine kinases?
KIT, PDGFR-a/B, and Lyn
689
In a study looking at the effect of neutropenia on outcome in dogs with multicentric lymphoma receiving CHOP, how did the presence of neutropenia influence the median first remission duration and MST?
Neutropenia - 1st remission = 851 days, MST = 952 days
No neutropenia - 1st remission = 219 days, MST = 282 days
P = < 0.01
690
Methyldiazonium ion and 5-aminoimidazole are the active metabolites of which chemotherapy drug?
Dacarbazine
691
Sentinel lymph node (SLN) mapping with regional lymphoscintigraphy has been performed to identify the draining lymph node in dogs with dermal mast cell tumors. What percent of dogs had SLN that were different from the anatomically closest lymph node?
42% (8)
692
Which tumor type is most commonly associated with neutrophilic inflammation on cytology?
Squamous cell carcinoma
693
Cells with a single large vacuole that displaces the nucleus to an eccentric location are referred to as?
Signet ring cells
Seen most commonly with tumors of secretory origin (Salivary gland tumors, mammary gland tumors)
694
```
Which type of thymoma in dogs carries a better prognosis?
A) Epithelial predominant
B) Mixed
C) Lymphocyte predominant
D) Null type
```
C) Lymphocyte predominant
695
What cytologic feature can help to differentiate adrenal carcinoma from pheochromocytoma?
Adrenal cortical tumors often contain few-to-many discrete clear vacuoles. Pheochromocytomas lack distinct cytoplasmic vacuoles and will stain positively with silver stains (Grimelius) and express synaptophysin and chromogranin A.
696
A dog has a rapidly growing SQ tumor on it's flank. Cytology shows pleomorphic mesenchymal cells with many criteria of malignancy, lack of inflammation, and cells are embedded in a lightly eosinophilic matrix that aligns the cells in streaming rows. What is the most likely diagnosis?
Myxosarcoma
697
Which histochemical stain can be used to confirm the presence of lipid within neoplastic mesenchymal cells as would be seen with a Liposarcoma?
Oil Red O
| Sudan black
698
A mass in the cecum of a dog is aspirated via US guidance. The report shows highly cellular sample consisting of long thin mesenchymal cells arranged in aggregates and linear bundles. Nuclei are often elongate or "cigar-shaped" and pleomorphism is mild. What is the most likely diangosis?
Leiomyosarcoma or GIST
Withrow pg. 124
699
A mass of the tongue in a dog is aspirated. Results show monomorphic population of individual round or polygonal cells containing numerous fine pink cytoplasmic granules and a central round nucleus. Electron microscopic examination reveals the pink granules to be numerous mitochondria. What is the most likely diagnosis?
Rhabdomyoma --> "granular cell tumor"
700
You receive a cytology report with history that just says "mass on a dog". Results show individualized pleomorphic spindle-shaped cells with low numbers of elongate strap cells demonstrating cross-striations within the cytoplasm. The strap cells have several round-to-oval nuclei arranged in a linear row. Few multinucleated cells seen. What is the most likely diagnosis?
Rhabdomyosarcoma
701
What is the cell of origin for giant cell tumors of bone?
Osteoclast
702
A large amount of purple/magenta extracellular matrix that envelops and often obscures the neoplastic cells is characteristic of which mesenchymal tumor type?
Chondrosarcoma
703
What IHC features distinguish periarticular HS from synovial cell sarcoma?
SCS: vimentin (+), cytokeratin (+), and CD18 (-)
HS: vimentin (+), cytokeratin (-), CD18 (+)
Some pathologist suggest SCS should be called "cytokeratin-positive joint associated sarcoma"
704
What is the MST for SCS differentiated by grade?
Grade I = 365 - 1460 days
Grade 2 = 156 - 1095 days
Grade 3 = 183 days
Overall MST = 455 - 967 days
705
Which breeds have a familial tendency for Bone Cysts?
Doberman Pinschers and Old English Sheepdogs- often young and present because of mild - mod lameness.
706
How can you cytologically differentiate melanophages from metastatic neoplastic melanoblasts in a lymph node?
```
Melanophages = COARSE collections of melanin within phagolysosomes
Melanoblasts = FINE granulation
```
707
In which mesenchymal tumors is multinucleation common?
1) Histiocytic sarcoma
2) Feline VAS
3) Rhabdomyosarcoma
4) Malignant fibrous histiocytoma
5) Osteosarcoma--> but multinucleated osteoclasts are not part of the neoplastic population of cells as opposed to the other tumor types.
708
What is a tingible body macrophage?
Macrophage containing nuclear debris from tumor cells (apoptosis). May be seen with lymphoma.
709
Large granular lymphoma is thought to arise from which 2 cell types?
1) Cytotoxic T-cells
| 2) NK cells
710
Which tumor type has been called a "wolf in sheep's clothing" because the cells resemble phagocytic macrophages found in inflammatory lesions and seldom exhibit criteria of malignancy?
Hemophagocytic Histiocytic Sarcoma
711
Which other tumor type can be hard to distinguish from reactive mesothelium and mesothelioma?
Carcinoma
712
The granules in feline and ferret mast cell tumors are best visualized with which histochemical stain?
Periodic acid-Schiff (PAS)
713
Name 2 histochemical stains which may help differentiate melanin from hemosiderin?
```
Melanin = Melanin bleach or Fontana-Masson
Hemosiderin = Prussian blue (iron stain)
```
714
Which histochemical stain can identify collagen fibrils such as those present in fibrosarcoma?
Masson's trichrome
715
Which histochemical stain can aid in differentiating a rhabdomyosarcoma from leiomyosarcoma as it enhances visibility of the cytoplasmic cross-striations present in skeletal muscle?
Phosphotungstic acid hematoxylin (PTAH)
716
Which histochemical stain can aid in diagnosis of granular cell tumor as it reacts with the intracytoplasmic lysosomes?
Periodic acid-Schiff (PAS)
Also useful for ferret and feline MCT
717
What diagnostic test is used to identify internal tandem duplications in exon 11 of the c-KIT gene in canine MCT?
PCR
718
Tumor necrosis rate of >90% for an osteosarcoma after neoadjuvant chemotherapy is associated with what % local control rate following limb-spare surgery?
91%
Tumor necrosis rate of 80 - 90% = 78% local control
Tumor necrosis rate of <80% = 28% local control
Withrow pg. 58
719
What is the term used to describe the abnormal transformation of a differentiated tissue of one kind into a differentiated tissue of another kind (non-neoplastic).
Metaplasia
Metaplasia should reverse or not progress with cessation of the chronic inciting stimulus. Eg. squamous metaplasia of the prostate gland. Metaplastic cells can be targets for carcinogenesis.
720
IHC for Rhabdomyosarcoma?
Vimentin (+), desmin (+), SMA (-)
721
What is the main use for the electron microscope?
To identify certain specific features that may help categorize tumor type:
Eg. intercellular junctions or basal lamina in epithelial cells, melanosomes in melanocytic cells, mast cell granules in mast cells, neurosecretory granules in neuroendocrine cells, or mucin droplets in certain epithelial cells.
722
During which phase of the cell cycle is the cell responsive to mitogenic signals?
G1
723
What is considered the molecular device that serves as the R point switch?
Rb protein
724
Phosphorylated p21 primarily inhibits which cell cycle proteins?
Cyclin D/CDK4,6 complex, thereby arresting cells in G1
725
The protein p21 arrests the cell cycle in which phase?
G1
726
Which cyclin-dependent kinase regulates mitosis?
CDK1 (together with Cyclin B)
727
Oncogene activation involves: (pick one)
A) Dominant gain of function
B) Recessive gain of function
C) Loss of heterozygosity
A) Dominant gain of function --> only one allele needs to be affected to obtain phenotypic change.
728
Which proto-oncogene has been shown to be amplified in a proportion of canine STS?
MDM2
729
Point mutations in which proto-oncogene have been identified in canine lung tumors?
K-RAS
730
Which tests can be used to quantify gene copy and identify gene amplification of proto-oncogenes?
1) Comparative genomic hybridization
2) Genotyping arrays
3) Southern hybridization
731
Which oncogene is frequently activated when FeLV integrates adjacent to it, leading to feline T-cell lymphoma?
myc
Transcription initiation in the viral long terminal repeat (LTR) proceeds into the adjacent oncogene, producing a hybrid mRNA.
732
What are the 3 main gene products of p53 transcription?
1) p21 --> cell cycle arrest
2) Bax --> apoptosis
3) MDM2--> targets p53 for degradation (ubiquitination). MDM2 can also suppress p53 transcription.
733
Which 2 proteins mediate the p53 response to stress?
1) DNA-dependent protein kinase (DNA-PK)
| 2) ATM kinase
734
What is the most frequently inactivated gene in human neoplasia?
p53
735
The Birt Hogg Dube equivalent syndrome in dogs (Renal carcinoma and nodular dermatofibrosis- RCND) and it's corresponding heritable factor (RCND gene) can be localized to which gene/chromosome?
Folliculin gene
| Chromosome 5
736
A genetic event provides a somatic cell with limitless replicative potential or another growth or survival advantage from other cells in the environment is referred to as:
A) Initiation
B) Promotion
C) Progression
A) Initiation
737
A genetic event that further adds to the cell’s ability to outcompete its neighbors in its environment, leading to its expansion as a recognizable tumor mass is referred to as:
A) Initiation
B) Promotion
C) Progression
B) Promotion
738
A genetic event that reinforces the cell’s malignant potential for invasion, tissue destruction, and metastasis, leading to clinical disease is referred to as:
A) Initiation
B) Promotion
C) Progression
C) Progression
739
Overexpression of what protein has been identified in cats with oral squamous cell carcinoma that were exposed to environmental tobacco smoke?
p53
740
What is the mean interval between TPLO and OSA diagnosis in OSA associated implants?
(Selmic et. al 2014)
5.3 years
| median 5.5 years in another study
741
What % of cats persistently infected with the feline leukemia virus actually develop lymphoid cancer?
20%
742
What is the rate of conversion from a viral infection to a neoplastic disease in cattle infected with BLV?
~1% of infected animals and occurs over a 7-8 year time line
Tumors in Domestic Animals pg. 286
743
What is the most common immunophenotype in cattle with large cell lymphoma?
B-cell
744
You receive flow results of a dog with peripheral lymphadenopathy: CD4-, CD8+, CD21+, CD45-, high expression class II MHC. What is your diagnosis?
T-zone lymphoma
Referred to as small clear cell lymphoma in some texts.
Tumors of Domestic animals pg. 270
745
You receive flow results of a dog with peripheral lymphadenopathy: CD4+, CD8-, MHCII-, CD21-, CD45+, What is your diagnosis?
T-cell lymphoma (most aggressive type)
746
What % of dogs with T-zone lymphoma will have lymphocytosis?
Approximately 50%, usually low grade (6000-15000/uL) and without cytopenias. Does not appear to indicate an increased rate of tumor progression.
747
What is the characteristic histologic appearance of Mantle Zone Lymphoma (B-cell)?
Neoplastic cells symmetrically surround germinal centers. Does not efface node or expand into perinodal tissues.
748
Which virus(es) has been suggested as a cause of equine sarcoids?
Bovine papillomavirus types 1 and 2
749
Feline sarcoma virus (FeSV) arises from the combination of which virus and proto-oncogenes in the cat's genome?
FeLV
750
Cats infected with which 2 FeLV subgroups often develop thymic lymphoma and myeloproliferative disease?
A and B
751
Which FeLV subgroup is associated with development of severe erythroid hypoplasia and anemia causing death within 1-2 months in cats?
C
752
What % of feline fibrosarcomas are virally induced?
2% (FeSV)
753
What was the mean time between experimental infection with FeLV to tumor production?
5.3 months
Withrow pg. 24
754
What is the active ingredient in Boswellia that reduces synthesis of leukotrienes by inhibiting 5-LOX?
Triterpenes
Antineoplastic activity = induce antiproliferation, differentiation, and apoptosis in leukemia cell lines.
755
Silymarin has been shown to enhance cellular proliferation in rodent models of which type of neoplasia?
Mammary tumor- likely through stimulation of estrogen-receptor signaling by silymarin
756
Which herbal treatment may inhibit chemotherapy induced apoptosis or negate antioxidant effects especially when used in combination with doxorubicin?
Curcumin
757
Which herbal treatment may inhibit certain isoforms of the CYP450 family thereby potentiating chemotherapy toxicity?
Silymarin
758
What is the active ingredient of Bloodroot?
Sanguinarine
Causes strong and rapid apoptotic responses through several modes of cell death, including an early and severe glutathione-depleting effect.
759
What % of dogs live longer than 30 weeks if their MCT was present for >28 weeks prior to surgery?
83% (vs. 25% if present for <28 weeks)
760
IHC to differentiate lymphangiosarcoma from HSA?
LYVE-1 and PROX-1
MST 168 days for 3 dogs w/out treatment
MST 487 days for 5 dogs with sx alone
1 dog tx with surgery, RT, chemo ST 574 days
761
In 56 healthy Beagle dogs, what % of LN aspirates contained mast cells?
24%
762
What is the sensitivity of ultrasound for detecting mast cell infiltration to the spleen or liver?
```
Spleen = 43%
Liver = 0%
```
763
In dogs with cutaneous MCT or STS, the extent of local tumor margins was upgraded by ____% with US and _____% with CT.
```
US = 19%
CT = 65%
```
764
What other diseases may cause peripheral mastocytosis in dogs aside from MCT?
```
Acute inflammatory disease (Parvo)
Inflammatory skin disease
Regenerative anemias
Neoplasia other than MCT
Trauma
```
765
In dogs presenting with visceral MCT, what % of buffy coat and bone marrow aspirates reveal MC dissemination?
Buffy coat = 37%
| Bone marrow = 56%
766
Based on the metric approach for surgical treatment of canine MCT, what surgical margins are recommended for low and intermediate grade MCT respectively?
```
Grade 1 (Low) = 1cm
Grade 2 (Intermediate) = 2cm
```
767
In a study of STS of the distal limbs undergoing wide local excision with healing by second intention, what % healed completely?
93.5%, median of 53 days.
768
2 year control rate for stage 0 incompletely excised (no gross disease) MCT of low- or intermediate grade followed by RT?
85 - 95%
769
Approximately what % of MCT with surgically incomplete margins will recur?
10 - 30%
770
What was the ORR for dogs with MCT treated with tiamcinolone alone? (Case JAVMA 2018)
80% (1 CR, 3 PR, 5 dogs)
Other groups included +/- steroids, chemo and RT (ORR = 67%) with median TTP of 63 days.
771
What is the RR of single agent prednisone for intermediate or high grade MCT?
20%, another report says 70 - 75%
Those dogs with tumors that expressed low levels of glucocorticoid receptor had MCTs that were resistant to prednisone therapy in one study.
772
What is the ORR of canine MCT to Palladia?
42.8%
773
What is the ORR of canine MCT with KIT mutation to Palladia?
69%, (vs. 37% for those without, about 2x as likely to respond if they have the mutation)
Although more recent studies have failed to confirm a higher response to TOC in c-kit mutant MCT.
774
A recent study investigated the combination of TOC, pred and hypofractionated RT in dogs with unresectable and/or metastatic MCT. What was the ORR?
76.4%, with 59% achieving CR and 17.6% PR.
| Overall MST was not reached with a median follow up of 374 days (1 year).
775
Which drug has been reported for use in cases of severe hemorrhage secondary to MCT heparin release?
Protamine sulfate (heparin antagonist)
776
What % of feline cutaneous and splenic/visceral MCT were found to have c-kit mutations?
67%
| Primarily exons 8 and 9
777
What % of cats with cutaneous MCT will present with multiple tumors?
20%
778
A 2 yo Siamese presents to you with multiple cutaneous masses (firm, pink, hairless). Cytology shows sheets of histiocytes that lack distinct cytoplasmic granules and are accompanied by randomly scattered lymphoid aggregates and eosinophils. About 15% of the cells are mast cells. What is the most likely diagnosis?
Histiocytic Mast Cell Tumor
Can be initially misdiagnosed as granulomatous nodular panniculitis or deep dermatitis.
779
IHC for Feline MCT?
Vimentin (+), a-1 antitrypsin (+), KIT (+)
780
In a study of cats with cutaneous MCT treated with strontium, what was the control rate and MST?
Turrel JAVMA 2006
Control rate = 98%
MST = > 3 years
Withrow
781
What was the MST for cats with MCT of the eyelids undergoing surgery +/- Rt or cryotherapy?
MST = 945 days
782
What % of cats with cutaneous MCT also have splenic involvement?
7% (3/41)
783
Which exon is typically affected with human MCT?
Exon 17
784
On histopathology, a local draining LN from a dog with an intermediate grade MCT is found to contain: > 3 individualized mast cells in a minimum of 4 HPF but no aggregates seen. Which Weishaar category is this?
HN1 = Pre-metastatic
785
What is the ORR for MCT when Palladia and CCNU are combined?
46 - 50%
786
What was the reported ORR of Paccal Vet for treatment of canine MCT?
(Rivera et. al BSAVA 2013)
59%
787
What was the ORR for alternating VBL/CCNU protocol in dogs with unresectable MCT?
Rassnick et. al VCO 2010
65%
Overall median PFS in dogs treated in adjuvant setting = 489 days, better for metastatic grade II (954) vs. grade III (190d).
788
In the immunologic response to tumor cells, proteins derived from the tumor cells will be processed and loaded onto MHC Class I via which major pathway?
Cross-presentation pathway
MHC Class I --> presented to CD8+ Cytotoxic T cells
789
One key function that differentiates DC from other professional APC such as macrophages and B cells, is their ability to activate _________ ?
Naïve T cells.
790
What is the pathogen associated ligand for TLR4?
Lipopolysaccharide (LPS)
791
What is the name of the enzyme expressed in developing T and B cells that functions in genomic DNA rearrangements that bring together different gene segments and splice them into a combined exon?
Recombination activation gene recombinase (RAG recombinase)
792
Which part of the TCR is the reason for its enormous diversity?
The B chain
B chain has 3 rearranged gene segments (V, D = diversity and J regions) that undergo rearrangement, compared to the A chain which is rearrangement of the V and J segment expressed with a constant (C) region.
793
The specificity of the TCR for a defined peptide bound in the groove of an MHC molecule is determined by which region of the TCR?
Complementary determining regions (CDRs)
794
Which 2 molecules facilitate interaction between T cell and DC?
DC - intercellular adhesion molecule (ICAM)
| T cell - leukocyte function associated antigen (LFA)
795
The TCR on CD4+ T cells binds which molecule?
MHC II (present on APC)
Eg. Melanoma vaccine--> TCR on CD4+ cells binds to MHC II on APC presenting tyrosinase to activate them.
796
The TCR on CD8+ T cells binds which molecule?
MHC I (present on all cells)
797
Th2 cells primarily target:
A) Intracellular pathogens
B) Extracellular pathogens
C) Tumor cells
B) Extracellular pathogens and parasites
Mediate humoral antibody response. Produces IL-4 that binds to CD4+ T cells and results in signal transduction.
798
Th1 cells primarily target:
A) Intracellular pathogens
B) Extracellular pathogens
C) Tumor cells
A) Intracellular pathogens (viruses, intracellular bacteria)
Produces IL-2, TNF-a, IFN-y and induce IL-12 production by APC. Augments CD8+ CTL type response.
799
What is the action of CTLA-4?
Competes with CD28 for binding to CD80 and 86 on mature APC--> sends signal to activate IDO--> metabolizes tryptophan and inhibits T-cell proliferation.
CTLA-4 upregulated after TCR engagement on T cells, also constitutively found on T regs.
800
Why does loss of MMR lead to resistance to alkylators?
It is the futile cycling of repair reactions through MMR (removing bases opposite O6 methylguanine) and repeated attempts to repair that actually produces the SSB and DSB.
801
Bacillus Calmette-Guerin (BCG) is a form of nonspecific immune modulator. Which bacteria did it originate from and what human tumor is it used to treat?
Mycobacterium bovis
Administered intravesically and prevents recurrence of superficial bladder carcinoma. Mostly Th1 response.
802
Which breeds are most commonly diagnosed with oral melanoma?
Scottish Terrier, Golden Retrievers, Chow Chows, Poodles, and Dachshunds.
803
What are the primary factors that determine the biological behavior of an oral melanoma in a dog?
Site, size, stage, and histologic parameters.
804
Which mutations have been identified in canine melanoma?
Downstream constitutive activation of ERK
Small subset have exon 11 c-KIT mutation (10.2%)
Somatic mutations in NRAS and PTEN
805
Which 4 factors are assessed with the Michigan State Melanoma Prognostic Panel?
1) Ki67* highly predictive of prognosis
2) Nuclear atypia
3) MI
4) Degree of pigmentation
Mitotic count is helpful in predicting prognosis, but is not as predictive as nuclear atypia or Ki-67 index
806
Which 4 IHC markers are used in the Michigan State Melanoma (diagnostic) panel?
1) Melan-A
2) TRP-1
3) TRP-3
3) PNL-2
807
What % of dogs with oral melanoma and lymphadenopathy will have LN mets?
70%
808
What % of dogs with oral tumors and lymph node metastasis showed contralateral dissemination?
62%
30% of oral melanomas had mets to all 4 lymph centers. (Skinner et. al VCO 2016)
809
What are the recommended surgical margins for malignant melanoma?
2-3 cm if possible.
| 1cm for benign cutaneous melanocytoma.
810
What is the RR for dogs with oral melanoma treated with carboplatin?
28%
811
What is the RR for dogs with oral melanoma treated with cisplatin and piroxicam?
18%
812
In a study of high dose ascorbate on canine melanoma cells, what was the proposed mechanism of reducing cell viability?
Induction of apoptosis via the activation of Bax.
813
What was the MST of dogs with stage II/III oral MM treated with surgery followed by CSPG4 electrovaccination?
(Piras VCO)
```
MST = 684 days
DFI = 477 days
```
vs. control (MST 200, DFI 180)
814
What is the grade of dose-limiting toxicity for gastrointestinal symptoms in Phase 1 dose-finding clinical trials?
Grade III
815
What is the grade of dose-limiting toxicity for myelosuppression/hematologic in Phase 1 dose-finding clinical trials?
Grade IV
Grade IV preferred because these events are usually considered manageable with supportive care, generally transient, and often clinically silent (Withrow pg. 293)
816
What are the 3 options for starting dose in a Phase 1 Trial?
1) 33% the "no observable adverse event level" (NOAEL)
2) 10% of the severe toxicity dose in the most sensitive species
3) 50% the MTD in laboratory Beagle dogs.
817
What is the regulatory agency for veterinary biologic medications such as the Oncept IL-2 medication?
USDA
818
Protocols that utilize animal subjects in clinical research must be approved by which committee?
Institutional Animal Care and Use committees (ACUC)
819
An investigation of Masitinib in dogs with pulmonary metastatic OSA where all dogs receive Masitinib for 4 weeks, and then those with stable disease or better are randomized to drug continuation or discontinuation (placebo) and followed with monthly evaluation is an example of which type of study?
Randomized Discontinuation Trial (RDT)
Best suited for cystostatic drugs.
820
What is the name to describe when DNA sequences differ at single nucleotide positions within the genome?
Single-nucleotide polymorphism (SNP).
Occur at introns & exons. The best example is altered drug metabolism because of modifying effect on the cytochrome P450 metabolizing enzyme.
821
A randomized phase II trial of a TKI in the treatment of epidermal growth factor receptor 2 (HER2/neu) positive breast cancer was initially designed to enter 164 patients. Interim analysis after 34 patients were enrolled was performed and showed 67% CR compared to 25% CR with standard of care. The trial was stopped and the drug moved to phase III early due to promising results. This is an example of what type of Adaptive trial design?
Bayesian approach
822
A drug has been FDA approved for treatment of canine HSA. A study is performed looking at the use of this treatment in dogs with renal dysfunction. What phase is this study?
Phase IV
823
A randomized multicenter study of liposome encapsulated cisplatin (SPI-77) versus standard of care carboplatin in dogs with appendicular OSA was performed. No difference was observed between treatment groups. What phase is this study?
Phase III
824
What are the 3 "stopping rules" for clinical trials?
1) Investigational treatment is clearly better than the control
2) Investigational treatment is clearly worse than the control (less activity or more toxic)
3) The investigational therapy is not likely to be better
825
What are the dosing increase % for cytotoxic agents using Fibonacci method?
100%, 67%, 50%, 40%, 33%
826
What is the most common cause of cancer drug failure in oncology clinical trials?
Toxicity or inactivity
827
Based on the standard method of a phase I dose escalation scheme (3 x 3 cohort design), what would be the next appropriate step if there are > 2 patients that experience a dose limiting toxicity?
Dose escalation is stopped and this dose level declared the MTD.
828
Based on the standard method of a phase I dose escalation scheme (3 x 3 cohort design), what would be the next appropriate step if there is 1 patient that experiences a dose limiting toxicity?
Enter at least 3 more patients at this dose level. If none of these 3 patients experiences DLT, proceed to the next dose level. If one or more of this group suffer DLT, then dose escalation is stopped and this dose is declared MTD.
829
What is the recommended phase 2 dose MTD?
Less than or = to 1/6 patients with DLT at highest dose level below the maximally administered dose
830
In dogs what is the most common tumor to metastasize to the brain?
Hemangiosarcoma
831
3 most common RBC morphology seen with canine HSA?
1) Schistocytes
2) Acanthocytes
3) Nucleated RBC
832
What % of dogs with HSA will present with thrombocytopenia?
75 - 97%
833
Which 3 ECG findings may be associated with ruptured cardiac HSA?
1) Decreased amplitude QRS complex
2) Electrical alternans
3) Ventricular arrhythmias
834
What are the recommended surgical margins for cutaneous HSA?
1 - 2 cm
835
What % of dogs with grossly abnormal livers had liver metastasis on biopsy? (Clendaniel et. al JAAHA)
50%
836
What is the reported MST of dermal HSA?
| Szivek et. al VCO
987 days
837
In a study of dogs with cardiac HSA treated with DOX, what was the ORR and MST?
```
ORR = 41%
MST = 116 days
```
838
In one study of 59 dogs with splenic masses, what % of patients developed arrhythmias post-operatively?
24%
839
What was the ORR for dogs with splenic HSA (either stage I/II or stage III) treated with VAC?
Alvarez et. al JAAHA 2013
86%
Overall MST = 189d, not significantly different between dogs of stage I/II (189d) or stage III (195d).
840
Which Kallikrein (a serine proteinase) has been studied extensively for it's utility as a serum cancer biomarker?
Prostate specific antigen (PSA) in human prostate cancer.
841
What % of tumor cells injected directly in to the blood will form tumor nodules?
<1%
Tannock pg. 227 (usually orders of magnitude lower)
842
Monoclonal Ab targeting RANKL?
Denosumab
RANKL is produced by osteoblasts which stimulates myeloid progenitor cells to differentiate into osteoclasts. OPG is a RANKL antagonist.
843
What is a TIMP?
Tissue inhibitor of metalloproteinases
844
Which MMPs family are involved in NOTCH activation?
ADAMs
845
EMT is associated with loss of expression of which cell-surface and cytoskeletal proteins? (4)
1) E-cadherin
2) Cytokeratin/desmoplakin
3) Zona occludens 1 (ZO-1)
4) Laminin
846
EMT is associated with gain of expression of which cell-surface and cytoskeletal proteins? (4)
1) N-cadherin
2) Vimentin
3) Fibronectin/B-catenin
4) a-SMA
847
Which transcription factors play a role in EMT? (4)
1) TWIST
2) Snail
3) Slug
4) LEF
848
Using expression microarray, which gene has been identified as the most consistently upregulated gene in relation to tumor progression?
OPN
Tannock pg. 236
849
How long after infection do clinical signs of papilloma manifest?
4 - 6 weeks
850
How long after TVT transmission does tumor growth generally appear?
2 - 6 months
851
A critical threshold of which cytokine secreted by TIL must be reached to trigger TVT into R phase?
IL-6
852
You perform FNA and impression smear of a mass from the nasal mucosa of a male intact dog. The mass is oozing serosanguineous fluid and is friable. Cytology demonstrates uniform discrete round to polyhedral-shaped cells with moderately abundant pale blue cytoplasm and an eccentrically located nucleus, with occasional binucleation and mitotic figures. There are numerous discrete clear cytoplasmic vacuoles, which you send a picture of to your clinical pathologist friend she refers to it as a “string of pearls.” What is the most likely diagnosis?
TVT
853
Which 2 immune cells are most important in TVT regression?
Cytotoxic CD8+ T-cells
| NK cells
854
Which immunotherapy is likely to be effective against TVT according to newest withrow?
Check point inhibitors
855
Temporal separation of events in the cell cycle is what ensures that DNA is replicated only once per cell cycle. At which phase of the cell cycle is the Pre-RC complex able to assemble on the origin?
G1
Licensed origins can only fire during S phase. This limits each origin to a single firing event and prevents re-replication of the DNA (Tannock pg. 194)
856
What is the function of a centrosome?
Organelles that sit at either spindle pole and generally act to organize microtubules.
857
```
The CIP/KIP family of CKI's (p21, p27, p57) primarily inhibit:
A) CDK4/CDK6 binding to CYCLIN D
B) CDK2 binding to CYCLIN A or E
C) CDK1 binding to CYLIN A or B
D) Non-specific
```
D) Non-specific
858
```
The INK4a family of CKI's (p16, p15, p18, p19) primarily inhibit:
A) CDK4/CDK6 binding to CYCLIN D
B) CDK2 binding to CYCLIN A or E
C) CDK1 binding to CYLIN A or B
D) Non-specific
```
A) CDK4/CDK6 binding to CYCLIN D
859
What are the targets of the APC/C complex?
Targets cyclin A, B, Geminin and SKP2 for degradation. Levels of APC/C complex remain high during G1 phase.
860
Which 3 proteins are known as the "pocket proteins" and become phosphorylated by CYCLIN D-CDK4/6 during G1 phase of the cell cycle?
1) Retinoblastoma protein (RB)
2) p107
3) p130
Causes release of E2F transcription factor--> encodes Cyclin E, Cyclin A2, and EMI1 (inhibitor of APC/C)
861
What is the molecular basis for the Restriction (R) Point?
Switch from:
- Low to high CDK2
- High to low APC/C activity
862
What is the function of WEE1 and MYT1?
Inhibit Cyclin B-CDK1 complexes by phosphorylating amino acids of CDK1.
863
The events of early mitosis are orchestrated by which 4 mitotic kinases?
1) CYCLIN B-CDK1
2) Polo-like kinase 1 (PLK 1)
3) AUR A
4) AUR B
864
Which is faster- cell cycle or cell growth?
Cell cycle
The events of the cell cycle can be accomplished in far less time than it takes to double the mass of the cell--> thus coordination between cell growth and cell cycle must exist.
865
Platinum adducts are primarily removed/repaired by which pathway?
Nucleotide excision repair (NER)
866
Which protease is responsible for cleaving the cohesion subunit that binds centromeres of sister chromatids through cohesin? What is the inhibitor of this protein?
Separase
Separase cleaves cohesin at the sister chromatid centromeres to allow them to pull apart. Securin inhibits separase. APC/C is required to ubiquinate Securin to allow separase to cleave cohesin permitting anaphase to proceed.
867
What 2 events can lead to activation of the Spindle Assembly Checkpoint?
1) Kinetochores that are not attached to microtubules
| 2) Insufficient levels of tension between centromeres
868
How does the Spindle Assembly Checkpoint prevent anaphase upon activation?
The SAC prevents full activation of APC/C, thus stabilizing securin and CYCLIN B from ubiquination/degradation. Securin and CYCLIN B suppress separase and maintain the metaphase state.
869
Apoptosis induced in response to inadequate cell-matrix interactions is known as?
Anoikis
870
Which oncogene when activated induces p53 dependent apoptosis? Via which apoptotic pathway?
c-MYC - Mitochondrial (intrinsic) pathway
Directly and via ARF-MDM2-p53 pathway
871
What are the executioner caspases?
CASP 3, 6, and 7
872
In a study of MC CYC as maintenance for dogs with appendicular OSA following limb amp and carboplatin (Matsuyama et. al JAVMA 2018), what was the MST of dogs receiving carbo followed by MC? What % discontinued treatment due to SHC?
MST = 480 days (vs. 458d carbo alone)
| 58% d/c treatment due to SHC.
873
What is the ORR and MST for ifosfamide salvage therapy for canine metastatic OSA?
ORR = 11.8%
| Median survival duration = 95 days.
874
Based on the current literature, what cytotoxic chemotherapeutic has the greatest response rate when intravenously administered to dogs with stage III OSA?
Ifosfamide
875
What % of dogs undergoing SRT and surgical stabilization for OSA experienced complications?
94% (88% major, 50% requiring amputation)
| Most common complication was infection
876
What was the MST for small breed dogs (<15kg) with OSA undergoing curative intent treatment?
(Amsellem et. al 2014 JAVMA)
415d
877
What is the MST & median duration of pain control when stereotactic radiation therapy is used for canine vertebral osteosarcoma? (Swift et. al VCO 2017)
MST = 139 days
Median duration of pain control = 77 days
Neuro improvement in 44%, Pain improvement in 83%
878
What percent of canine primary osteosarcoma tumor samples overexpress HER2?
40%
879
Oxygen (%) levels below what threshold will activate oxygen sensitive signaling pathways?
3% or below
880
Which primary chemokine has been implicated in it's role in metastasis and ERK1/2 MAP kinase and Akt activation leading to poor prognosis in a number of tumors?
CXCR4
- Downregulated in canine OSA by zoledronate
- Increased in feline MGT especially metastatic cells.
881
What effect does hypoxia have on mTOR?
A) Activation
B) Inhibition
B) Inhibition
882
Warburg effect is a shift towards which metabolic pathway?
A) Oxidative phosphorylation
B) Aerobic glycolysis
C) Citric acid cycle (Krebs cycle)
B) Aerobic glycolysis
In tumors, occurs even under normal O2 conditions. More rapid but less efficient in terms of ATP generated per molecule of glucose compared to oxidative phosphorylation--> requires increased glucose uptake. Excess lactate and carbonic acid is produced.
883
Which molecule in the PI3K pathway is known to be an important driver of the tumor glycolytic phenotype?
AKT1
By increasing expression of glucose transporters, phosphorylating key glycolytic enzymes (hexokinase, PFK-2), inhibiting FOXO, and activating mTOR.
884
What % of cats were found to have 2 different types of intracranial neoplasia concurrently?
10%
Withrow pg. 583 (old)
885
What is the most common secondary brain tumor in dogs?
Hemangiosarcoma (29%) (followed by pituitary tumor)
886
What is the most common secondary brain tumor in cats?
Lymphoma (followed by pituitary tumor)
887
Gliomas have a tendency to affect which part of the brain?
Diencephalon and cerebellum
888
The majority of feline meningioma are of which 2 subtypes?
1) Meningothelial
| 2) Psammomatous
889
Choroid plexus tumors in general tend to occur in which ventricle?
fourth (only choroid plexus papillomas occured in the lateral ventricls)
Withrow pg. 584
890
What % of dogs with primary brain tumor had concurrent unrelated neoplasia?
23%
Withrow (old) pg. 584 and 589
891
Most common clinical signs in cats with brain tumors?
Seizures (23%--> more common with glioma/lymphoma)
| Non-specific (20%--> lethargy, inappetence, anorexia)
892
```
A brain tumor causing ataxia, dysmetria, intention tremors, vestibular abnormalities and menace reaction deficits (normal vision) is most likely located where?
A) Cerebrum
B) Diencephalon
C) Pituitary
D) Cerebellum
```
D) Cerebellum
893
```
A brain tumor causing alteration of consciousness, dysfunction of CN III - IV and obvious gait/proprioceptive abnormalities is most likely located where?
A) Cerebrum
B) Diencephalon
C) Medulla
D) Cerebellum
```
C) Medulla (brainstem from midbrain through medulla)
894
In a study by Gardner et al, VCO 2013 on oral fibrosarcomas, what was the PFS and MST for dogs treated with a combination of surgery and radiation?
```
PFS = 300 days
MST = 500 days
```
895
What is the accuracy of predicting primary brain tumor type based on MR images?
70%
Withrow (old) pg. 585
896
What % of canine meningiomas are typically invasive at surgery?
1/3 (33%)
897
What is the median survival time for dogs with presumptive gliomas treated with CCNU?
Moirano et. al 2017 VCO
138 days
Dogs with duration of clinical signs >16d prior to diagnosis lived longer.
898
What percentage of intracranial canine meningiomas have been shown to express COX-2?
87% (vs. 0% in gliomas)
899
What is the perioperative mortality (< 1 month) for cats after excision of intracranial meningiomas?
(Cameron et. al Vet Surg 2015)
6% (MST = 37 months)
900
What is the reported progression free survival time in dogs with incompletely excised intracranial meningiomas that are treated with megavoltage RT?
35 months
Withrow (old) pg. 587
901
What is the difference between Stereotactic radiosurgery (SRS) and Stereotactic radiation therapy (SRT)?
SRS and SRT are very similar, but SRS delivers a large dose of radiation on a single day and SRT has a fractionated treatment schedule.
902
What was the MST for dogs with glioma undergoing surgery?
185 days
903
Which histotype of Meningioma carries the best prognosis following surgery?
Transitional (MST 1254 days)
Withrow pg. 588
904
What is the most common primary spinal tumor in cats?
Lymphoma
905
What is the most common primary spinal tumor in dogs?
Meningioma
Most frequently arise in cervical SC, Boxers may be predisposed.
906
```
What is the most common location for canine spinal tumors? Options are:
A) Extradural
B) Intradural/extramedullary
C) Intramedullary
D) Mixed
```
A) Extradural (48%)
Withrow pg. 589
Meningioma/MNST usually intradural/extramedullary
Feline spinal lymphoma usually extradural
907
```
What is the most common location for spinal neprhoblastoma? Options are:
A) Extradural
B) Intradural/extramedullary
C) Intramedullary
D) Mixed
```
B) Intradural/extramedullary
908
What is a prominent clinical feature of extradural and intradudral/extramedullary spinal neoplasia prior to onset of proprioceptive and voluntary motor deficits?
Spinal hyperesthesia
909
What was the MST for 16 cats undergoing surgery for spinal meningioma?
426 - 518 days
910
What was the MST of 9 dogs with spinal tumors (mostly meningioma = 6) treated with sx + RT?
17 months
911
A palpable mass may be found in the axillary region in ___% of dogs with peripheral nerve sheath tumors
37%
912
What was the MST and recurrence rate of cats with PNST treated with surgical excision or amputation?
MST = 21.5 months
| Recurrence rate = 20%
913
What is the most common location for spinal lymphoma in cats?
Thoracic and lumbar spine
| --> Usually extradural.
914
What is the most common spinal segment affected by grade I meningiomas in dogs?
C1 - C4
Grade II --> more aggressive and occurring in thoracolumbar region in younger dogs.
915
What % of cats with nasal lymphoma will have systemic failure of disease at nonnasal sites following response to RT?
13 - 16%
916
What are some of the intrinsic markers of hypoxia?
HIF-1a, GLUT-1, carbonic anhydrase-9, and osteopontin (OPN)- can be detected using IHC.
Tannock pg. 369
917
What is the annual dose limit for radiation workers?
0.05 Sv = 50 mSv = 5 rem
918
What are the 3 syndromes that can lead to death as a result of whole body irradiation?
1) Hematological (2 - 8 Gy) death in 12 - 30 days
2) Gastrointestinal (5 - 15 Gy) death after 1 week
3) Neurovascular (>20 Gy) rapid death
Following doses > 2Gy, humans will develop early nausea and vomiting within hours of radiation (prodromal syndrome), which may be controlled with 5-HT3 antagonists (ondansetron)
919
Name 3 examples of an organ with functional subunits arranged in parallel.
Lung, liver, kidney
920
Name 2 examples of organs with functional subunits arranged in series
Spinal cord, intestine
921
What % of grade 3 PNST will invade the spinal cord?
50%
922
Where do intermuscular lipomas tend to occur?
Between semitendinosus and semimembranosus muscles.
923
What is the metastatic rate for hepatic, intrabdominal, and dermal leiomyosarcoma respectively?
```
Hepatic = 100%
Intrabdominal = 50%
Dermal = 0%
```
924
Median disease-specific ST in dogs with presumptive intracranial trigeminal nerve PNST when treated with SRS?
745 days
925
What is the MST of cats with cutaneous HSA treated with wide surgical resection?
1460 days
| vs. 60 days without surgery
926
What is the MST for dogs with splenic mesenchymoma?
12 months
927
MST of dogs with compartmental resection of peripheral nerve tumors with limb preservation that had non infiltrative margins post surgery?
2227 days
| overall MST 1300 d, dirty margins = 487d
928
FNA of STS: how many incorrectly diagnosed? how many nondiagnostic?
15% incorrectly diagnosed
| 23% non diagnostic
929
Which 3 IHC markers can differentiate vaccine associated sarcomas from non-injection site fibrosarcomas in cats?
1) PDGF
2) EGF
3) TGF-B
930
What is the overall MST for incompletely resected nonoral STS treated with postoperative RT?
2270 days,
Local tumor recurrence = 16 - 60%
Median time to local recurrence = 700 - 798 days
931
IHC to differentiate PNST from fibrosarcoma?
S-100 and vimentin
932
Dogs with a mitotic index great than ____ are more likely to have local tumor recurrence and shorter survival in one study of 39 dogs treated with orthovoltage and doxorubicin as radiation sensitizer.
9/10 HPF
933
Metastasis is 5x more likely when dogs have a STS with a mitotic rate of ___ or more mitotic figures/10 HPF.
20
934
What is the MST for dogs with 10 or fewer, 10 - 19, and 20 or more mitotic figures/10 HPF?
10 or fewer = 1444 days
10 - 19 = 532 days
>20 = 236 days
Withrow pg. 369
935
What % of feline injection site sarcomas are high grade?
59% grade III
| only 5% grade I
936
What was the MST of dogs with presumed solitary ocular lymphoma (PSOL) without systemic involvement?
769 days (vs. 103 days for dogs having systemic involvement.
937
What Flow marker most commonly associated with T-zone lymphoma?
CD45-, MHCII+, CD21+
938
Flow markers with best PFI and MST (T-cell lymphoma)
| - Deravi et al 2017 Vet Immunology
CD4-, CD8+, MHCII+ (PFI = 756d, MST = 541d)
939
Flow markers with worst PFI (T-cell lymphoma)
CD4-/CD8+/MHCII- (PFI = 35 days)
940
Flow markers with worst MST (T-cell lymphoma)
CD4+/CD8-/MHCII- (MST = 160 days)
