Exam 3 - D.O.G Flashcards
steps of carcinogenesis
initiation
promotion
progression
initiation
nature of change to cells?
cellular phenotype?
reversible or irreversible?
DNA mutation, nonlethal
no permanent morphologic change
irreversible
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
progression
nature of change to cells?
cellular phenotype?
reversible or irreversible?
DNA mutations, successful subclones, heterogenous population
morphological change - malignant phenotype
irreversible
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
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
tumor suppressor genes
examples
negative feedback on growth, slow down proliferation
1. retinoblastoma gene
2. p53 gene
Retinoblastoma (pRB)
tumor suppressor gene
DNA binding protein
control of cell cycle
p53
tumor suppressor gene
DNA proofreading - delay for repair
Apoptosis
BRCA1
tumor suppressor gene
repairs ds break in DNA
breast, ovary cancer
how does retinoblastoma gene mutations support the “2 hit” hypothesis of carcinogenesis
usually recessive alleles - thus must lose both for loss of control
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
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
routes of metastasis
direct location invasion
blood vascular system (e..g embolism)
lymphatics
implantation (w/in body cavity)
transplantation
metastasis typically has a ______ distribution but this pattern may also be due to ________ transformation
multifocal
multicentric
example of transplantation metastasis
canine transmissible venereal tumor
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
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
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
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.
- vaccine-associated sarcomas in cats
- 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
