Lucky Dip Flashcards
What is the Warburg effect?
Cancer cells experience a metabolic shift from oxidative respiration to an energy efficient aerobic glycolytic profile.
Activating mutations of the BRAF gene lead to constitutive activation of the MAPK pathway. The most common alteration in BRAF are point substitutions at
Valine 600 (V600). In dogs with iUC it is usually V595E
Which JAK/STAT inhibitor is used in veterinary medicine?
Oclacitinib
What is Knudson’s 2 hit hypothesis?
That most tumor suppressor genes require both alleles to be inactivated (recessively acting cancer gene), either through mutations or through epigenetic silencing, to cause a phenotypic change (cancer development). This was proven with the Rb1 locus (retinoblastoma tumor suppressor gene). Homozygous loss of the wild-type Rb1 locus correlated with retinoblastoma development.
Which virus is associated with the development of Burkitt’s lymphoma?
Epstein-Barr virus (EBV)
What is the Hayflick limit?
The eventual loss of replicative potential (cellular senescence). The time to the cessation of cell division correlates closely with critically eroded telomeres (called telomere signal-free ends).
What is the name of the complex that degrades proteins that are tagged with ubiquitin?
26S proteosome
List the stages of apoptosis
- Rounding up of the cell
- Plasma membrane blebbing
- Cytoplasm shrinkage
- Alteration of membrane asymmetry
- Condensation and fragmentation of the nucleus
Late stage: fragmented into apoptotic bodies that are eliminated by phagocytic cells without triggering inflammation.
What is the action of RANKL
Receptor activator of nuclear factor kappa betta ligand (RANKL) is released by osteoblasts. It activates myeloid progenitor cells to differentiate into osteoclasts that can digest bone structures, creating space for establishment of metastasis. Denosumab is a monoclonal Ab targeting RANKL, approved for treating patients with bone metastasis.
How many tumor cells necessary for 1g (1 cm) of tumor (smallest clinically detectable mass)
1 x 10^9
What is the action of DNA methylation
Covalent addition of a methyl group at position 5 of a cytosine (C) nucleotide (5mC), typically positioned close to a guanine residue (G), occuring mostly in CpG islands (regions dense in adjacent C and G nucleotides) found at the promoter region of genes. Typically results in gene-SILENCING.
What is the normal diffusion distance of oxygen from tumor blood vessels?
150-200 um
Name for the novel hedgehog pathway inhibitor?
Saridegib
What is the name of the most common HDAC inhibitor?
Vorinostat
What is the name of the most common PARP inhibitor
Olaparib
What are the markers for cancer associated fibroblasts?
a-smooth muscle actin (a-SMA), fibroblast specific protein-1 (FSP-1)/S100, neuron-glial antigen-2 (NG-2), PDGFR-beta.
Which enzyme functions in alkylator-induced DNA repair
MGMT
What are the solvents used for paclitaxel and docetaxel respectively that allow for IV administration?
Paclitaxel = Cremophor EL, Docetaxel + Polysorbate 80
These solvents cause severe hypersensitivity reactions in dogs and require significant pretreatment with antihistamines and steroids and prolonged infusion with continued monitoring.
New water soluble formulation of paclitaxel (Paccal Vet) may lead to increased use of this drug in vet med.
Feline cutaneous MCT response to lomustine?
20 cats: 2 CR, 8 PR = 50% ORR
Which drugs are radiation sensitizers
Doxorubicin, carboplatin, actinomycin D, gemcitabine
What toxicity is associated with 5-FU in cats
Fatal CNS toxicity
Which anthracycline may be administered orally?
Idarubicin
Why is cyclophosphamide relatively platelet sparing?
High levels of aldehyde dehydrogenase in the bone marrow (which deactivates cyclophosphamide)
What is the active metabolite of cyclophosphamide?
Phosphoramide mustard
Which chemotherapy agent must you give MESNA with?
Ifosfamide
Which drugs are severe vesicants?
Doxorubicin, vinca alkaloids, mechlorethamin, actinomycin D
What are the IHC markers for melanoma?
Melan-A, S-100, PNL2, tyrosinase
IHC marker for thyroid carcinoma (epithelial)
Thyroglobulin (+)
IHC marker for thyroid carcinoma (c-cell)
Synaptophysin (+), chromogranin (+), thyroglobulin (-)
IHC markers for MCT
Vimentin (+)
Tryptase and CD117 (KIT) (+)
+/- chymase, MCP-1, and IL-8 (+)
Which IHC stain can differentiate between canine urinary bladder transitional cell carcinoma and other carcinomas?
Uroplakin III
Which IHC marker can confirm a diagnosis of hemophagocytic histiocytic sarcoma?
CD11d
Which IHC markers are positive with hemangiosarcoma?
Factor 8 (vWF), CD31
GIST IHC markers
CD117(KIT), CD34, DOG-1, and S-100
Which IHC markers are used to distinguish pheochromocytoma from adrenocortical carcinoma?
chromogranin A and synaptophysin
Markers for feline progressive histiocytosis
CD1a, CD11c/CD18, CD5, Iba-I, CD204
Which type of radiation induced DNA damage is most important for cell killing caused by exposure to ionizing radiation?
DNA double strand breaks
The main mechanism of cell death after irradiation is
Mitotic catastrophe: cells with damaged DNA attempt to divide resulting in progeny with an incomplete genetic complement and are unviable.
What is the annual dose limit for radiation workers?
0.05 Sy = 50 mSv = 5 rem
Which radiolysis product of water is responsible for the molecular damage caused by the indirect action of ionizing radiation?
OH* (Hydroxyl radical)
Cells in which phase of the cell cycle are most sensitive to radiation?
G2/M phase
Cells in which phase of the cell cycle are least sensitive to radiation?
Late S phase
What is the most common site for canine chondrosarcoma?
Nasal cavity
Is canine gastrointestinal lymphoma more commonly T or B cell?
T cell 63% vs B cell 37%
Which exons are typically mutated with c-kit in feline mast cell tumors?
Exon 8 and 9 (extracellular domain)
65% of cats will carry this mutation (most were 8, more common with splenic MCT).
Which gene was recently associated with MCT development in golden retrievers?
GNAI2-associated with hyaluronic acid synthesis
How many dogs with MCT present with multiple tumors?
11-14%
In dogs, c-kit mutations appear to be associated with what percent of intermediate and high grade MCT?
25-30%
How many dogs with MCTs located in the muzzle present with regional metastasis?
50-60%
This does not necessarily indicate a worse long term prognosis, as the MST for dogs with metastatic disease was 14 months.
What is the reported MST for poorly differentiated MCT with the presence of LN metastasis?
194 d
vs 503d for dogs with no metastasis
What is the incidence of bone marrow involvement in canine MCT
2.8%
Which parasite has been associated with development of sarcoma in dogs
Spirocerca lupi
What is the most common paraneoplastic syndrome associated with thymoma in the cat?
Exfoliative dermatitis
What 3 abnormalities characterize a syndrome associated with mutation in the canine Birt-Hogg-Dube (BHD) gene in GSD?
- Multiple uterine leiomyomas
- Bilateral renal cystadenocarcinomas
- Nodular dermatofibrosis
Mutation in FLCN-tumor suppressor gene coding for protein folliculin. Also seen in Alsatians.
Which gene expression is common in canine gastric carcinoma
Exon 11 of c-kit gene, HER-2 (58%)
Which testicular tumor is most often associated with hyperestrogenism?
Sertoli cell tumor
Which characteristics predict a worse outcome for dogs diagnosed with B cell lymphoma?
Large cell, low levels of class II MHC expression
What is the most common location of feline appendicular osteosarcoma?
Distal femur and proximal tibia
Which tumor location is most suitable for limb sparing surgery in dogs affected by OSA?
Distal radius or ulna
Which protein is necessary for metastasis in murine models of osteosarcoma and associated with shorter DFI in dogs with osteosarcoma?
Ezrin
Which breed is predisposed to bile duct carcinoma?
Labrador retrievers, sex predilection for females
Which monoclonal antibody targets HER-2 positive tumors in humans?
Trastuzumab
What percentage of HSA occur primarily in the liver?
4-6%
Which virus is associated with HCC in humans?
Hepatitis viruses B and C
Which cells do carcinoid cells arise from?
Neuroendocrine cells
Contain secretory granules that may contain substances such as 5-hydroxytryptamine (seratonin), secretin, somatostatin, and gastrin, among others.
IHC for cytokeratin and serotonin may be positive.
What histopathologic factors are associated with worse prognosis for canine SQ MCT?
Mitotic index greater than 4
Multinucleation
Invasiveness
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
What is the RR of AGASACA to Palladia
25% PR, 63% SD, total clinical benefit rate = 88%
What is the MST of dogs with nasal carcinoma without treatment?
95 days (3 months)
What is the MST of cats with lymphoma without treatment?
53 days
What % of cats treated with SRT for functional pituitary adenoma developed hypothyroidism?
14%
Which tumors are known to express ABCB1
Canine lymphoma, mammary tumors, feline primary pulmonary carcinoma
What percent of dogs with testicular tumors have bilateral tumors?
50%
What percent of dogs with sertoli cell tumors will present with signs of hyperestrogenism?
50%
What percent of dogs will have greater than 1 testicular tumor type?
4-20%
What percentage of dogs with prostat 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)
What percent of prostatic carcinomas had COX-2 expression in dogs?
75-88%
What is the MST of dogs with prostatic carcinoma treated with NSAID alone?
6.9 months
What percent of dogs with iUC are reported to have urethral involvement?
56%
What is the MST of cats with iUC treated with a variety of treatments?
261
11 cats treated with meloxicam = 311 days. More than half were away from the trigone
What percent of dogs with iUC are reported to have prostatic involvement?
29%
What is the MST of dogs with renal HSA in a retrospective study of 14 dogs?
278 d
In a phase I clinical trial of intravesical mitomycin C, what were the most significant complications?
Marked myelosuppression and GI upset - indicating there was some systemic absorption occuring
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 what percent of cases?
30%
What percent of cats with meningioma present with multiple tumors?
17% (Withrow page 583)
What is the most common type of glioma in dogs?
Oligodendroglioma (previously reported to be astrocytoma) (new Withrow)
What is the MST for dogs with CNS lymphoma treated with a variety of treatments?
171 days
What is the MST for dogs with presumptive glioma treated with CCNU?
178 days
What is the reported MST for cats with cerebral meningiomas treated surgically?
23-37 months
685 days in another study (2 years)
What proportion of cerebral meningiomas in cats will recur following surgical treatment?
20.6-25% (median TTR 285 days)
What is the MST of dogs with meningioma treated surgically with conventional techniques?
7 months
What percent of feline brain tumors are detected incidentally?
20%
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
Which breeds of dogs are predisposed to spinal nephroblastoma at a young age?
GSD and Golden retrievers
Which spinal cord segments do nephroblastomas arise from?
T9-L2
Which is the most common spinal nerve root affected by PNST?
Caudal cervical region (C6-T2)
What is the most common tumor of the canine conjunctiva?
Melanoma
Older, female, weimaraner and possibly GSD/large breed dogs may be predisposed
What is the most common tumor of the third eyelid in dogs and cats?
Adenocarcinoma (85%)
What is the average latency period for cats to develop ocular posttraumatic sarcoma?
5 years
67% are males or neutered males
In cats with orbital neoplasia, what percent had radiographic signs of orbital bone lesions?
59%
15% had pulmonary metastasis.
What is the average latency period for cats to develop ocular posttraumatic sarcoma
5 years
67% are neutered males
In cats with orbital neoplasia, what percent had radiographic signs of orbital bone lesion?
59%
15% had pulmonary metastasis
What percentage of canine anterior uveal melanomas demonstrate metastasis?
25%
What percent 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
What percentage of dogs with large B cell lymphoma will have normal CBCs but exhibit bone marrow involvement when assessed via flow cytometry?
15%
What is the characteristic marker for T zone lymphoma
CD45-
What was the MST of T zone lymphoma in Seelig et al 2014
657 days
What percent 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%
In a retrospective study by Childress et al, what were the 4 negative prognostic factors identified in dogs with DLBCL undergoing CHOP chemotherapy?
- Thrombocytopenia
- Greater age at diagnosis
- Higher neutrophil count
- Higher serum globulin concentration
What is the sensitivity and specificity of AUS for detection of splenic involvement of lymphoma?
Sensitivity 100%, specificity 23%
Which breed has been described to have lymphocytic plasmcytic inflammatory bowel disease that progressed to GI lymphoma?
Basenji
Which dog breeds may be overrepresented in cases of alimentary lymphoma?
Boxers and Sharpei
What percent of dogs with lymphoma present with hypercalcemia?
10-40%
What is the name of the syndrome of cutaneous T cell epitheliotropic lymphoma progressing to circulating malignant cells in humans?
Sezary syndrome
What chromosomal aberration has been detected in dogs with naturally occuring 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
What percent of dogs with multicentric lymphoma have diffuse pulmonary infiltration?
27-34%
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
For dogs that have completed the CHOP chemotherapy protocol for lymphoma, what percentage of dogs will successfully be reinduced by the same protocol more than 2 months after completion of treatment?
80-90%
What is the most common lymphoma related paraneoplastic syndrome?
Anemia
What percent of dogs with lymphoma will have ocular involvement/uveitis?
33-50%
What percent of dogs with lymphoma are reported to have monoclonal gammopathies? Which type of lymphoma?
6%, usually B cell LSA
What are the B cell markers?
CD79a, CD20, CD21, Pax5
Although dogs with TZL can express CD21
What are the T cell markers?
CD3 (pan), CD4 (helper), CD8 (cytotoxic)
What classifies as a LARGE lymphocyte?
Greater than 2x an RBC or larger than a neutrophil
Intermediate = 1.5-2 x RBC, same size as neutrophil
What percent of dogs with multicentric lymphoma?
35% (response duration of 43 d)
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)
What is the name of the monoclonal antibody against CD20 used in humans with B cell non-hodgekins lymphoma
Rituximab
What is the MST for colorectal lymphoma in dogs receiving chemotherapy and what is the dominant immunophenotype?
MST - 1845-2352
B cell
What is the reported MST of dogs with low grade GI lymphoma treated with chlorambucil and prednisone?
1.5-2 years
What is the response rate for cutaneous lymphoma to chemotherapy?
40-80% median remission duration is 3-6 months
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%
Approximately what percentage of dogs with T zone lymphoma have been reported to be Golden Retrievers?
40%
What is the median PFI and overall ST for canine nodal marginal zone lymphoma?
PFI - 5 months
Overal ST = 8.5 mo
What is the median PFS for cutaneous lymphoma treated with Tanovea?
38 days
What is the response rate and median remission duration for cutaneous lymphoma treated with CCNU?
80%, median remission duration = 3 months
What is the concordance rate of pre-treatment bx STS to final dx?
59%
29% underestimate, 12% overestimate
What was the MST for dogs treated with surgery and adjuvant carbo for oral melanoma (+/- RT)?
MSTS = 440 d, PFI = 259 days
What percentage of dogs with chronic lymphocytic leukemia were reported to develop Richter’s syndrome?
5%, median survival = 41 days
Normalization of lymphocytes counts occur in what percent of treated CLL cases?
70%
In a study of metastatic cancer of unknown primary, what percent were diagnosed as carcinoma?
57%
MST = 30 days
Primary site not identified on full body CT in 95% of dogs
What proportion of telangiectatic OSA were reclassified as HSA of bone when stained with VWIII-related antigen or VWf?
20%
In a study of 40 dogs with systemic mastocytosis, which chemotherapy protocol provided the best outcome?
Lomustine + vinblastine + prednisone – MST = 227 d
Palladia MST = 118 days
What was the MST for feline large granular lymphoma receiving a variety of treatments?
MST = 21 days, small subset (7.3%) survived greater than 6 months
MST was significantly shorter in the case of substage b, circulating neoplastic cells, lack of chemotherapy administration, and lack of treatment response.
Which chemotherapeutic drugs are inhibitors of ribonculeotide reductase?
Gemcitabine, cytarabine, hydroxyurea; reason for radiation sensitivity?
What percent of cats with renal transplant receiving cyclosporine developed neoplasia in Wormser et al 2014?
22.5% (56% of which were lymphoma – 10-13%)
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?
6x neoplasia
7x lymphoma
What percent of cats with T cell GI lymphoma exhibit epitheliotropism?
40%
What percent of cats with lymphoma have pulmonary involvement?
12.8%
2% had no gross abnormalities (peribronchial-vascular invasion most common histo abnormality)
5% were B cell vs T cell
5% + FeLV
What is the immunophenotypic classification for Hodgkin’s like lymphoma in cats?
T cell rich B cell lymphoma
Nasal lymphoma in cats are primarily what phenotype?
68% B cell (20% T cell, 12% mixed)
Renal lymphoma in cats in Australia are primarily what phenotype?
B cell
What percent of cats with renal lymphoma will have extension to the CNS?
40-50%
What percent of CNS lymphoma are FeLV+ antigeneic?
17-50%
Which area of the spine most commonly affected by CNS lymphoma?
Thoracolumbar
What percent of hypercalcemic cats are diagnosed with lymphoma?
10%
What is the reported sensitivity of PARR for feline lymphoma?
80% specificity has not been established
What percent of cats with LGL (6/8 were treated with CHOP) were reported to live longer than 6 months?
7.3%
What is the rerported MST of cats with LGL treated with chemotherapy?
63 d (2 months)
Methylation of the promoter region of p16 has been identified in ______% of feline B cell lymphoid tumors
33%
What is the reported sensitivity and specificity of splenic ultrasonographic appearance (ie a moth eaten parenchyma) for the diagnosis of feline malignancies?
Sensitivity 13.2%, Specificity 84.8%
Splenic mass>1cm, Sensitivity 21%, specificity 94.7%
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
What is the increased risk associated with FeLV cats in developing lymphoma?
62 x
FIV infection associated with 5 x risk
Mast cells can be seen in up to ______% of aspirations from thymoma?
50%
What percent of renal lymphoma will be bilateral?
> 80%
What percent of renal lymphoma will have AUS evidence of other organ involvement?
33%
What percent of renal lymphoma will have AUS evidence of other organ involvement?
33%
What percent of cats who relapsed following COP based protocol subsequently responded to single agent DOX?
22%
What was the response rate for cats with lymphoma treated with Lspar?
30%, much shorter asparagine depleting effect in cats (lost by 7 days)
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
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
ALL in cats is primarily what phenotype?
T cell, about 60-80% FeLV positive
What phenotype is most common with mediastinal lymphoma?
T cell
Nasal = B cell
What is the reported MST of 20 cats with high grade GI LSA when treated with surgical resection and CHOP based chemotherapy?
420 days
Nasal lymphoma immunophenotype?
3/4 B cell
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
What percent of cats with lymphoma will respond to Elspar?
30%
Missense mutations in what genes have been identified in dogs with AML?
FLT3, C-KIT, RAS
What is the tendency for the myeloid:erythroid ratio to be in Polychythemia vera?
Normal
What are the markers for megakaryocyte lineage in dogs and cats?
Acetylcholinesterase, vWF/fVIII platelet glycoprotein, CD41
What are the markers for neutrophils?
Peroxidase, sudan black B, chloracetate esterase
What are the markers for monocytes?
Nonspecific esterases (alpha-naphithyl acetate esterase or alpha-naphthyl butyrate esterase) especially if they are inhibited by sodium fluoride
What is the marker for basophiles?
Omega exonuclease, + for chloracetate esterase activity
What are the markers for myeloid cells?
MPO and CD11b
What is the most common type of DNMT3L (methylation) mutation identified in dogs with AML?
Missense mutation in exon 7
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
You are treating a dog with chronic myelogenous leukemia. After inducing with hydroxyurea (20 mg/kg BID), what hematologic parameter is used to gauge your dose reduction?
Leukocyte count falls to 15000-20000 cells/uL
Philadelphia chromosome or BCL-ABL translocation between chromosomes 9 and 22 in humans with CML. What are the equivalent chromosomes in dogs with CML?
Chromosomes 9 and 26
What percent of dogs with MM will have abnormal PT/PTT?
50%
Hyperviscosity syndrome occurs in what percent of dogs with multiple myeloma? Which immunoglobulin is most frequently associated with this?
20-40% (IgM)
What percent of dogs with multiple myeloma develop Bence Jones proteinuria?
25-40%
What are the known negative prognostic factors in dogs with MM?
Hypercalcemia
Bence Jones proteinuria
Extensive bony lysis
Which IHC stains are typically used for extramedullary plasmacytosis?
MUM-1, IRF-4, thioflavin T
When is staging most important for extramedullary plasmacytosis?
Cutaneous plasmacytosis, solitary osseus plasmacytoma, GI extramedullary plasmacytoma (higher risk of metastasis)
Less important for cutaneous, oral, and colorectal plasmacytoma
What percent of cases with cutaneous plasmacytosis had LN or abdominal visceral involvement?
30%
What is the recurrence and metastatic rate for solitary cutaneous and oral plasmacytomas following surgery?
5% and 2% respectively
What is the MST for colorectal plasmacytoma treated with surgery +/- chemo?
15 months
What is the MST for Waldenstroms macrogaammaglobulinemia (IgM) treated with chlorambucil?
11 months, 77% RR
What percent of dogs had concurrent splenic and right atrial HSA on echocardiogram in one study?
8.7%
Previous necropsy studies suggest about 25%
What are the IHC markers for hemangiosarcoma?
VWf/fVIII related antigen or CD31/platelet endothelial cell adhesion molecule
What percent of grossly abnormal livers in dogs with confirmed splenic HSA were confirmed to contain HSA metastasis in one study?
50%