Flashcards in Neopalsms- Nelson Deck (15):
Define neoplasia, and state the underlying pathogenic mechanism of neoplasia. Describe the key difference between benign and malignant neoplasms.
Neoplasia = abnormal mass of tissue, new growth
i. Stimulus causes genetic alterations in single cells
ii. Alterations passed onto progeny & subsequent cells
iii. Allows excessive and unregulated proliferation that becomes autonomous
Benign = cannot spread to other tissues
Malignant = capability to metastasize
List the four types of genes typically mutated in cancer
Growth-inhibiting tumor suppressor genes
Genes that regulate programmed cell death
Genes involved in DNA repair
Define proto-oncogene, oncogene, and oncoprotein
Proto-oncogene → un-mutated normal
Oncogene → mutated or overexpressed version of proto-oncogenes
Oncoprotein → results of oncogene
For a given proto-oncogene, how many alleles are typically mutated in order to generate an activating mutation?
Only one allele needs to become mutant to create an effect
Explain the rationale of performing Her2/neu testing in breast cancer
Her2/neu → over expression of cell membrane epidermal growth factor receptor, can treat with monoclonal antibody to that receptor
Explain the rationale of performing KRAS mutation analysis in colon cancer.
presence in colon cancer can be predictive of lack of response to certain forms of chemotherapy
Define tumor suppressor gene, and list some of the functions of tumor suppressor genes.
Tumor suppressor gene → products of these genes inhibit cell proliferation, preventing uncontrolled growth
Regulation of cell cycle
Regulation of nuclear transcription
Regulation of cell differentiation
Explain the “two hit” hypothesis for suppressor gene defects
Two hit hypothesis → both alleles of tumor suppressor genes need to be damaged for loss of growth inhibition
State the malignancies associated with inheritance of BRCA1/2 and APC mutations.
BRAC1/2 mutation → regulates DNA repair, implicated in break ovary and prostate carcinomas
APC mutation → prevents nuclear transcription, implicated in colorectal carcinoma
Describe how over expression of BCL-2 can lead to follicular lymphoma.
BCL-2 → gene products regulate and prevent apoptosis by limiting the release of cytochrome C
Describe how overexpression of telomerase can lead to limitless replication
Shortening of telomeres is a way to signal cell age, and when it gets old, p53 recognizes that and induces apoptosis, up regulation of telomerase prevents this from happening
Describe how cancer cells can initiate neoangiogenesis. What cytokine is typically involved?
Describe the number of alleles that need to be mutated for dysfunction of DNA repair. Describe the defect in Hereditary Nonpolyposis Colon Cancer Syndrome (HNPCC).
DNA repair genes themselves are NOT oncogenic, but abnormalities greatly enhance occurrence of mutations in other genes
HNPCC → increased risk for carcinomas of the colon-Inactivation of genes involved in DNA mismatch repair
Explain the Warburg effect, and how this effect is used in the imaging of cancer.
Even with ample oxygen, cancer cells have increased coercion of glucose to lactose (fermentation) via the glycolytic pathway.