Neoplasia 3 Flashcards
Describe the mechanisms to alter DNA, causes, & the source.
- Mechanisms
-mutations = change in nucleotide seq
-chromosomal alteration
-epigenetic change = heritable change in gene expression resulting from something other than change in DNA seq - Cause
-spontaneous
-ionizing radiation
-chem carcinogens (non lethal genetic damage)
-oncogenic virus - Source
-inherited in germ line
-acquired somatic mutation
Describe germ line mutations.
-mutation passed on in the ova or sperm
-all cells of affected progeny
-involved in:
>pediatric cancer
>family predisposition
>ppl w more than 1 type of cancer
-humans inherit 60 new mutation that occur in ova or sperm
-<10% human cancer have inherited mutations
Describe acquired somatic mutations.
-occur in individual cells & their progeny (not passed on in germ line)
-spontaneous mutation unavoidable in individual life time (10^10 mutations/gene in a life time)
-accumulate over time = association between old age & cancer
Bright side:
>DNA repair mech
>most mutation are lethal to cell not animal
>multiple mutation needed for cancer
Describe radiation.
*all forms are carcinogens - able to initiate & promote tumorigenesis w cont exposure
1. Ionizing
-x ray, gamma ray
-eject e- from mol
-DNA strand breaks
2. UV
-UVB
-form pyrimidine dimmer in DNA = overwhelms nucleotide excision repair
-cats ears (cutaneous squamous cell carcinoma) & cows eyes (ocular squamous cell carcinoma)
Describe chemical carcinogens.
-chem metabolically transformed to become active
-associated w other cancer predisposing mutations
-EX: bracken fern ingestion, aflatoxin (moldy food - hepatoma in rainbow trout), hepatic carcinoma, dioxins, nitrosamines, polycyclic aromatic hydrocarbons (cig smoke)
-mechanisms:
1. Genotoxic - directly damage DNA
2. Cytotoxic - inc cell prolif due to cell injury
3. Mitogenic - inc cell prolif w/o cell injury
Describe oncogenic viruses.
-lg # of epidemiologically related animals
-affect young animals
-DNA stage during viral rep
-interrupt host gene by:
1. Come w their own oncogenes
-ex. Papillomavirus E6/E7 proteins inactivate p53 & other tumor suppressor genes
2. Insertional mutagenesis
-ex: retrovirus - avian leukosis
3. Immunosuppression
-ex: Mareks
Describe other causes of carcinogenesis.
- Hormonal
-hormonal stim of growth in target organ
-OVH in dog dec risk of mammary carcinoma - Chronic inflam/inf
-mech not understood - inflam cytokines stim cell prolif ?
-ex:
A) Esophageal sarcoma in dog w s. Lupi inf
B) Biliary carcinoma in cat & dog w liver fluke
C) Gastric carcinoma & lymphoma in humans w helicobacter spp.
Describe the para neoplastic effects - mechanisms of host damage.
- Direct effects
-organ/tissue destruction - Paraneoplastic syndromes
-occult neoplasm
-treatment or lethal
-symptoms due to spread or hormones
-indirect & remote effect caused by tumor cell prod rather than primary tumor & its metastasis
EX: cancer cachexia, cerebral atrophy secondary to oligodendroglioma
Describe tumor necrosis.
- Pathogenesis
-secondary to inflam in tumor
-trauma of tumor
-tumor outgrows its blood supply - Secondary inflam resp & cytokines (TNFa) impact host health
Describe cancer cachexia.
-animals w cancer show weight loss & debilitation
-loss of body fat & lean body mass, weakness, anorexia, anemia
-loss of fat + muscle + metabolic rate doesnt dec (vs starvation) *
-pathogenesis:
1. TNF, IL1, IL6, INFgamma, prostaglandins, PIF (Proteolysis inducing factor)
2. Anorexia, impaired digestion, nutrition demands of tumor, metabolic/endocrine changes
3. Cant fix w extra nutrition supplement
Describe endocrinopathies.
-consequence of neoplasm in endocrine organs (over/under produce hormone)
-non endocrine neoplasm make hormone active substance not normally found in tissue of tumor origin (ectopic hormone prod)
-EX: hypercalcemia of malignancy *
>prod of parathyroid hormone related protein by neoplasm
>90% of cases in dogs due to apocrine gland adenocarcinoma of anal sac
>lymphoma, multiple myeloma also common in dogs
Describe the 2 main mechanisms that cancer can lead to hypercalcemia.
- Local action on bone
-multiple myeloma or carcinoma that metastasize to bone - Tumor that secrete humoral factors
-stim bone reabsorption (PTHrP)
Describe hypertrophic osteopathy.
-dog & cat
-lameness
-X-rays show periosteal new bone growth
-space occupying thoracic lesions
-pathogenesis not known - abnormalities of growth hormone ?
Describe cytologic diagnosis.
-aspirate of mass
-faster, cheaper, less invasive than histology
-determine type of neoplasm & differentiate benign VS malignant
-histopath to confirm
-round cell tumor:
>mesenchymal neoplasm
>plasma cell tumor, histiocytoma, mast cell tumor, lymphoma, TVT
Describe margin assessment.
-surgical margin w surgical ink
>bc cant tell where the lab cut VS where the surgeon cut otherwise
>tissues slip apart from sample during transport/handling
>help orientate which margin is which (lateral VS deep)
-pathologist report if margins are clean or dirty based on absence/presence of tumor cells respectively
>can provide distance between tumor cells & sx margin
-complete excision imp prognostic factor
>clean margins dont mean complete excision
