Exam 3 - D.O.G Flashcards by AE G

steps of carcinogenesis

initiation
promotion
progression

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initiation
nature of change to cells?
cellular phenotype?
reversible or irreversible?

DNA mutation, nonlethal
no permanent morphologic change
irreversible

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promotion
nature of change to cells?
cellular phenotype?
reversible or irreversible?

clonal expansion of initiated cells, epigenetic changes (altered gene expression w/o altered DNA) - NO DNA mutation
morphological change
reversible

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progression
nature of change to cells?
cellular phenotype?
reversible or irreversible?

DNA mutations, successful subclones, heterogenous population
morphological change - malignant phenotype
irreversible

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proto-oncogene defintion
examples

normal genes promoting growth & differentiation

growth factors, growth factor receptors/transmembrane proteins, signal transducing proteins, nuclear regulatory proteins, cyclins and cyclin-dependent kinases

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oncogene definition and action

example

mutated proto-oncogenes resulting in proliferation of cancer cells

defective proteins all on/all off
overproduction of normal proteins by gene amplification (increased gene copy number)
overproduction of normal proteins by abnormal gene activity (abnormal regulation)
defective proteins by abnormally combined genes (chromosomal translocation)

BCR-ABL –> production of abnormal tyrosine kinase –> proliferation, survival of myeloid cells

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tumor suppressor genes
examples

negative feedback on growth, slow down proliferation
1. retinoblastoma gene
2. p53 gene

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Retinoblastoma (pRB)

tumor suppressor gene
DNA binding protein
control of cell cycle

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p53

tumor suppressor gene
DNA proofreading - delay for repair
Apoptosis

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BRCA1

tumor suppressor gene
repairs ds break in DNA
breast, ovary cancer

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how does retinoblastoma gene mutations support the “2 hit” hypothesis of carcinogenesis

usually recessive alleles - thus must lose both for loss of control

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characteristics of neoplastic cells
immortal or mortal
______ of anchorage dependence
_______ cell-cell adhesion
______ of contact inhibition
________ IC communication
________ motility
_______ requirement for growth factors
_____ or ______ cell surface antigens
_______ karyotype

immortal
loss of anchorage dependence
decrease cell-cell adhesion
loss of contact inhibition
altered IC communication
increased motility
decreased requirement for growth factors
altered or new cell surface antigens
abnormal karyotype

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properties cancer cells must acquire to metastasize

invade extracellular matrix
penetrate vascular basement membrane/endothelium
move into blood/lymphatics
embolize/adhere at new site
penetrate vascular wall
grow at new site w/ blood supply

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routes of metastasis

direct location invasion
blood vascular system (e..g embolism)
lymphatics
implantation (w/in body cavity)
transplantation

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metastasis typically has a ______ distribution but this pattern may also be due to ________ transformation

multifocal

multicentric

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example of transplantation metastasis

canine transmissible venereal tumor

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general mechanisms of clonal selection of tumor cells

selection for phenotypically superior tumor invasion, metastasis, evasion of immune response
benign, poor growth, non-viable, malignant, anaplastic

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tumor latency

-time between initiation and appearance of a clinically recognizable condition/lesion
-cancer dz of old age = latent for 30-45 years
-clinical detection needs certain # tumor cells

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steps in tumor angiogenesis

avascular tumor (relies on diffusion)
vascular tumor (more than diffusion)
angiogenesis - growth of new vessels from pre-existing ones, essential for metastasis
1. activation
2. formation

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examples of direct chemical carcinogens

do not require metabolism
- alkylating agents

example of indirect chemical carcinogens

metabolites are carcinogenic; the majority of carcinogens
- polycyclic aromatic hydrocarbons
- aromatic amines/Azo dyes
- aflatoxins
- nitrosamines
- metals

what determines species predilection and organ specificity

P450

role of hormones in cancer
common organs?
example

act as a promotor - drives cell proliferation = accumulation of random genetic errors
- endometrium, ovary, prostate, testis, thyroid

prolactin increases mammary gland proliferation = human breast cancer

what tumors can be found in turkeys or rainbow trout in response to aflatoxins

hepatocellular carcinoma
aflatoxins target liver

UV radiation. pyrimidine cross-linked formation in DNA, skin cancers are responsible for what types of tumors and in what species

squamous cell carcinomas in white cats, hereford cattle, beagles hemangiomas & hemangiosarcomas in short/light fur dogs

metallic orthopedic prosthesis or hardware could be responsible for what types of tumors in dogs

sarcomas

Give examples of 2 cancers associated with inflammation in veterinary species.

1. vaccine-associated sarcomas in cats 2. trauma-associated ocular sarcomas in cats

Helicobacter pylori species affected tumor type

gastric carcinomas in rodents, ferrets, cheetahs, humans gastric lymphoma in humans

Spirocerca lupi species affected tumor type

esophageal fibrosarcomas in dogs

Papilloma virus species affected tumor type

benign epithelial papillomas in many species squamous carcinomas in humans, rabbits, cats, dogs

shope papillomavirus or cottontail rabbit papillomavirus produces ______ in rabbits

cutaneous papillomas (warts), some progress to invasive carcinoma

what is the cause of equine sarcoids

bovine papillomavirus - 1

Herpes virus species affected tumor type

lymphoma in monkeys marek's disease (lymphosarcoma) in fowl lucke's renal carcinoma in frgs burkitt's lymphoma or nasopharyngeal carcinoma in humans

POX viruses species affected tumor type

fibromas & myxomas in squirrels

retroviruses (feline sarcoma virus and enzootic bovine leukosis) species affected tumor type

sarcomas in cats lymphoma in cattle

direct effects of tumors

SHOPLI space occupying, pressure atrophy, occlusion of passages, local tissue destruction, interference with vital function, and hemorrhage

indirect/paraneoplastic effects of tumors

infection, hormonal, cachexia, metabolic disturbances, hematopoietic (hypercoaguability, anemia), neuropathy

Cachexia mechanism

indirect multiple tumor types - non-specific

nodular dermatofibrosis

indirect secondary to renal carcinoma

hypertrophic osteopathy

indirect secondary to thoracic masses

anemia

indirect erythrophagocytosis or bone marrow depletion

eosinophilia

indirect mast cell tumor

lymphocytic leukemia

indirect anemia, hypercoaguability, immunosuppression

stomach ulcers, vomiting, melena

canine mast cell tumor

multiple myeloma

bony lysis, recruitment of osteoclasts

hypercalcemia

indirect parathyroid tumor, lymphoma, anal sac gland adenocarcinoma, apocrine gland carcinoma

hyperadrenocorticism

immunosuppression, hypercoaguability, dermatopathy, adrenocortical adenoma

hyperinsulinemia

islet tumor - insulinoma

ferret alopecia, weakness, erythroid aplasia, vulvar swelling, prostatic squamous metaplasia

adrenocortical adenoma (adrenal tumor) and insulinoma