The Etiology of cancer (Withrow) Flashcards
What tumor types have increased risk after castration or spay? Name specific breeds that are reported.
- Cardiac tumors (castration/spay)
- OSA (castration/spay, all & purebred dogs & Rotties castrated before 1yo)
- Prostatic tumors
- Urinary bladder TCC (castration)
- LSA (castrated: all and Goldens <1yo at castration; spayed, all)
- Splenic HSA (spayed; all Vizslas, Goldens >1 year of age at spay)
- MCT (neutered/spayed; spayed: all, Vizslas and Goldens)
What FeLV subgroup causes erythroid hypoplasia and severe anemia, leading to death within 1-2 months?
FeLV-C
What FeLV subgroup is highly cytolytic for T-cells and causes severe immunosuppression?
FeLV-T
What proto-oncogenes can FeLV subgroups recombine with?
MYC or TCR
What FeLV subgroup is associated with higher incidence of thymic LSA and myeloproliferative disease?
FeLV-B
___% of cats persistently infected with FeLV develop lymphoid cancer.
20%
____-___% of cats with non-lymphoid hematopoietic cancer test positive for FeLV.
70-90%
The risk for developing LSA is ___ times higher in FeLV+ cats, and cats with previous exposure to FeLV but are FeLV negative have ____ increase in the risk of developing LSA.
- 62
- 40-fold
___% of fibrosarcomas in cats are virally induced.
2%
Metastasis occurs in ___% of virally induced fibrosarcomas in cats.
30%
Cats infected with FIV and
FeLV are ___ times more likely to develop lymphoma or leukemia than if they had been infected with either virus alone. Cats with combined infections had a ___% greater likelihood of developing lymphoma or leukemia than noninfected cats.
5.6
77%
In HSA and B-cell LSA, two shared loci were identified on chromosome ___, suggesting these different tumors might originate from common lineage of hematopoietic progenitor cells.
5
For canine B-cell LSAs, the most recurrently mutated genes were ____, ____, and _____, which regulate signaling pathways of ____ and _____.
- TRAF3, FBXW7, and POT1
- Telomerase and autoimmunity
44% of Boxers with peripheral T-cell LSA were found to have mutations in what pathway?
PTEN-m-TOR
Canine HSA harbor somatic mutations of _____ and ___ in >50% of tumors.
TP53 and PI3CA
Somatic mutations of ____ are the most common genetic abnormalities in canine OSA.
TP53
What cancers have been associated with environmental tobacco smoke in dogs and cats?
Dogs:
- nasal carcinoma
- lymphoma
Cats:
- lymphoma (OR 2.4)
- Oral SCC (not significant but associated with 2-fold increase)
What cancers have been associated with pesticides, herbicides, and insecticides in dogs and cats?
Dogs:
- 2,4-D: LSA (controversial)
- industrial/urban areas: LSA
- Paints/solvents: LSA
- Professionally-applied pesticides: LSA
- Self-applied insect growth regulators: LSA
- Topical insecticides: TCC (enhanced in overweight/obese dogs)
- Scottish terriers exposed to phenoxy herbicides (2,4-D): TCC
Cats:
- flea collars: oral SCC
An increased risk of some canine cancers, including _____, _______, and ______ has been reported in urban/industrial settings compared to rural.
LSA, tonsillar SCC, nasal carcinoma
What canine cancer has been associated with increased exposure to magnetic fields?
lymphoma
In a study evaluating dogs undergoing MV RT with cobalt photons for acanthomatous epulides found an overall incidence of secondary radiation-induced tumors of ___%
3.5%
In a study of 2400 dogs undergoing TPLO found that median time to occurrence of OSA was ______ (if it occurred, which was rare).
4.5 years
In one study, cats ovariectomized at 6 months of age had a ___x reduction in risk of mammary tumor development. What does not increase risk?
7x
parity
Female golden retrievers spayed after 1 year of age are __x more likely to develop HSA than intact female dogs or dogs spayed early.
4x
Spayed Vizslas are ___x more likely than intact females to develop HSA.
9x
In a UCD study, ____ was the most common cause of cancer-related death in Golden Retrievers
HSA
What papilloma virus causes oral papillomas?
CPV-1
What papilloma viruses cause cutaneous papillomas and cutaneous pigmented plaques?
CPV-2 and CPV-6
Detection of ___ in tissues by IHC is often used to link papilloma infection to neoplastic transformation.
P16 protein
______ are a key feature of papillomaviruses in tumorigenesis.
E proteins
Clinical evidence of physical changes with CPV usually manifest _____ after experimental infection.
4-6 weeks
Canine papillomas generally persist for _____ in the mouth and _______ on the skin before undergoing spontaneous regression.
mouth: 4-6 months
skin: 6 months - 1 year
Canine cutaneous exophytic papillomas are most commonly found in olders dogs of what two predisposed breeds? Most lesions appear where?
Kerry blue terrier and Cocker spaniels
head, eyelids, and feet
Cutaneous inverted papillomas occur in ____ dogs.
young
Multiple pigmented plaques (papillomas) have been described in _____ and ____.
Miniature Schnauzers and pugs
Ocular papillomas frequently occurs in dogs ____-____ of age.
6 months - 4 years
What kind of cells have been shown to inhibit papilloma virus in dogs by activating macrophages?
CD4 T cells
What papillomavirus is associated with feline cutaneous viral plaques and Bowenoid in situ carcinomas?
FcaPV-2
Sarcoids occur in young cats and affect what sites?
head, neck, digits
Papilloma virus lesions commonly affect _____ in domestic cats and ____ in exotic species.
haired skin
oral cavity
Papillomas can be described histologically as epidermal hyperplasia accompanied by acanthosis, hyper-granulosis, hyperkeratosis, and ballooning degeneration of cells of the ______ and ______.
stratum spinosum and stratum granulosum
Histologic features of feline fibropapilloma are similar to equine sarcoids. List them
fibroblastic proliferation
hyperplasia of epidermis
rete ridges
What are the envelope proteins in FeLV? Which is a likely mediator of immunosuppresion and which is found in vaccines?
P15E: mediator of immunosuppression
GP70: Important component in vaccines as antibodies produced against this protein are neutralizing
____ is the antigen that is detected in IFA and ELISA tests for FeLV.
P27
What strain of FeLV integrates adjacent to MYC leading to overexpression and rapid development of mediastinal LSA?
Rickard strain of FeLV (FeLV-R)
_____ is a protein found on surface of FeLV and FeLV-induced neoplasms but not on non-neoplastic feline cells?
FOCMA
_____ is a polyionic dye used to treat filariasis in humans.
Suramin
Uptake of 18F-FDG in PET imaging correlates with increased expression of what protein?
GLUT-1
What tyrosine kinase receptor is major mediator of VEGF-mediated angiogenic effects?
VEGFR-2
INK4 mutation is associated with what canine cancer?
T-cell malignancies
______ mutation is associated with canine mammary carcinoma.
PTEN
Runx2 mutation is associated with what canine cancer?
OSA
What wavelength of light is associated with non-melanotic skin lesions in people and animals?
UV-B (280nm-320nm)
In canine mammary carcinoma, loss of the regulation of growth hormone production by the _____ receptor may contribute to malignant transformation.
progesterone
What virus is linked to Kaposi sarcoma in people?
Human herpes virus 8
Epstein-Barr virus is linked to what two cancers in people?
Burkitt LSA and nasopharyngeal carcinoma
Hepadnavirus (hepatitis B) causes HCC in what non-human species?
Woodchuck
Suramin inhibits ______ in RNA tumor viruses. At low doses, it inhibits _______, which may lead to chemosensitivity. List targets for suramin.
- reverse transcriptase
- fibroblast growth factor
- targets: basic FGF, PDGF, TGF-B, EGF, IGF-1
At cytotoxic doses, suramin is associated with what toxicity?
severe fatigue
neurotoxicity
anemia
coagulopathy
adrenal insufficiency
Low doses of suramin enhance activities of ______ and ______ in xenograft-mouse tumors.
paclitaxel and doxorubicin
Phase I study in 16 dogs with measurable tumors evaluated suramin as a chemosensitizer for doxorubicin. What was the dose used? Was toxicity mild, moderate, or severe? What was the objective partial response rate?
- 6.75 mg/kg IV 3 hours before doxorubicin every 2 weeks
- mild toxicity, comparable to doxorubicin monotherapy
- 13%
47 dogs were treated with suramin and doxorubicin following amputation for OSA. What was the median DFI and MST?
DFI: 7 months
MST: 12 months
What FeLV subgroup is antigenically similar to FOCMA?
FeLV-C
What are the only hematopoietic tumors that have not been associated with FeLV?
Mast cell leukemia, eosinophilic leukemia, plasma cell tumor, and polycythemia vera
> 70% of cats prior to FeLV vaccine development were found to be positive for what type of LSAs?
renal, ocular, spinal, mediastinal
The range of time from infection to tumor production in FeLV+ cats is ___-____.
1-23 months
Pulmonary anthracosis is positively associated with what canine cancer?
lung cancer
Cumulative kerosene or coal heat exposure was positively associated with what canine cancer?
sinonasal cancer
Cats that wear a flea collar have ___x risk for developing oral SCC.
5X
What substantially reduced risk of feline oral SCC in an epidemiological study?
use of flea shampoo
Cats with high canned food intake have been reported to have a ___x risk of oral SCC development. What type of canned food was independently associated with risk?
3-fold
tuna
FIV+ cats are __x as likely to develop tumors.
5x
Of 8,642 FeLV-infected cats presenting to North American Veterinary teaching hospitals, co-infections were seen in ___%, anemia in ___%, lymphoma in ___%, leukopenia or thrombocytopenia in ___%, and leukemia or myeloproliferative disorders in ___%.
- co-infections: 15%
- anemia: 11%
- LSA: 6%
- leukopenia or thrombocytopenia: 5%
- leukemia or myeloproliferative disorders: 4%
The prevalence of FIV infection in one cohort of cats with LSA was ___%
50%
In a survey study of 826 naturally FIV-infected cats examined by North American Veterinary teaching hospitals, the most common disease syndromes were: (hint: there’s 8)
- Stomatitis
- Neoplasia – lymphoma and cutaneous SCC
- Ocular disease – uveitis and chorioretinitis
- Anemia and leukopenia
- Opportunistic infections
- Renal insufficiency
- Lower urinary tract disease
- Endocrinopathies – hyperthyroidism and diabetes
In a study evaluating FeLV and FIV prevalence in 18k cats at vet hospitals and animal shelters, the rate of FeLV or FIV positivity was <___% and ___% for both positivity. Multivariable analysis found what risk factors for seropositivity? What were the reported ORs?
- <3%
- 0.3%
- Adults > juveniles (OR FeLV 2.5, FIV 2.05)
- Intact adult males > intact adult females (OR FeLV 2.4, FIV 4.66)
- Outdoor sick cats > indoor healthy cats (OR FeLV 9.0, FIV 11.3)
An older epidemiological study from 1980 found that FeLV+ cats had a higher mortality rate (______ in 1000 cat months) than negative cats (____ in 1000 cat months). The leading cause of death was _____ followed by ______. What was the relative risk for these causes of deaths in FeLV+ cats compared to negative cats? What were major risk factors for development of LSA? What factor decreased death rates in household?
- 34.6 deaths per 1000 cat months
- 9 deaths per 1000 cat months
- glomerulonephritis followed by LSA
- Relative risk GLN: ~10
- Relative risk LSA: ~10
- Risk factors for LSA: virus positivity and low Ab titer to FOCMA
- Older age
In a 2016 paper evaluating p16 immunostaining in 52 canine SCC cases, ___% showed moderate p16 immunoreactivity. CPV-1 was amplified in ___% of tumors. Did the results of this paper support a significant role of PVs in canine SCC? Was p16 the cause of p16 immunostaining observed?
- 17%
- ~6%
- no and no
A paper evaluating oral papillary SCC in dogs found that >___% were over 6 years of age, all tumors were derived from the gingiva of dentate jaws with ___% affecting rostral aspects. ___% were advanced lesions but no local or distant metastasis was noted.
- > 75%
- 67%
- 91%
The incubation period of canine oral palpillomas is ____ with recovery within ___-_____.
1 month
2-3 months
Puppies in contact with _____ virus (which is not species-specific) may develop contagious pustular dermatitis or “___”, which is characterized by wart-like masses. These lesions typically disappear spontaneously.
- sheep-pox virus
- orf
In a 2018 Vet Path paper, IHC of canine oral papillary SCC was performed. Combined differences in immunolabeling for _______, ______, _____, and ______ discriminated between papillary SCC and oral SCC and AA. Papillomavirus was unlikely /likely to be associated with oral papillary SCC?
- AE1/AE3, 34BE12, p63, calretinin
- unlikely
