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Pathology 3-2

Duke PA pathology

What some examples of pre-neoplastic disorders? cirrhosis, HPV, UC
What are some factors that affect cancer risk? tobacco smoke, asbestos, radiation exposure, alcohol abuse
How do genetics affect cancer risk? cancer results from non-lethal genetic damage
Genetic hypothesis of cancer tumor arises from clonal expansion of the damaged cell
More on genetic hypothesis of cancer prediction that tumors have a monoclonal origin has been confirmed experimentally
carcinogenesis - molecular basis of cancer a multistep process at both phenotypic and genetic levels
tumor progression progressive acquisition of mutations leading to malignancy or metastasis
initiators stimulate mutation
promoters stimulate cell division
Damage to growth-promoting proto-oncogenes can result in what? cancer
Damage to growth-inhibiting tumor suppressor genes can cause what? cancer
Damage to genes that regulate cell death can cause what? cancer
Damage to genes that affect DNA repair can cause what? cancer
What is needed for cancer to allow unlimited cell division? activation of telomerase
oncogenes cancer-causing genes, drived from proto-oncogenes
Proto-oncogenes cellular genes that control normal growth and differentiation
insertional metagenesis retroviral promoter insertion near gene dysregulates its expression
What can activates oncogenes? insertional mutagenesis, point mutation, amplification, chromosomal translocation
mutation of ras oncogene mutant ras is always on
Where is ras anchored? cytoplasmic domain of growth factor receptors via a lipid group
What prevent addition of the lipid group, preventing ras localization? inhibitors of farnesyl transferase
What does translocation do to proto-oncogenes? places expression of protooncogenes under control of highly active promoters
What is the result of translocation? formation of hybrid genes that encode growth-promoting chimeric proteins
What gene does translocation occur in with Burkitt's lymphoma? c-myc
Are coding regions changed in Burkitt's lymphoma? they are unchanged
Over-expression due to translocation in mantle cell lymphoma cyclin D1 gene placed adjacent to IgH locus
Over-expression due to translocation in follicular lymphoma bcl-2 gene placed adjacent to IgH locus
Tumor suppressor genes products of these genes regulate cell growth (usually negatively)
What has to happen to tumor suppressor genes for cancer to take over? both copies of the gene have to inactivated - "recessive" cancer gene
What are the functions of tumor suppressor gene products? regulate the cell cycle, regulate nuclear transcription, cell surface receptors
What is the purpose of cell surface receptors? growth inhibition, adhesion
What does tumor growth depend on? balance between cell growth and cell death
What does dysregulation of apoptosis allow? accumulation of mutations that would otherwise by lethal
What is an example of dysregulation of apoptosis? bcl-2 overexpression in lymphoma
genes that regulate DNA repair mismatch repair genes
Are mutations in DNA repair genes oncogenic in and of themselves? no
What do mutations in DNA repair genes allow? allow mutations to occur in other genes during normal cell division
Can mutation of one gene transform cells? no - every human cancer has multiple genetic alterations including oncogenes and tumor suppressor genes
What does the rate of tumor growth depend on? growth fraction and the rate of cell loss
What does the growth fraction of tumors have an effect on? has a profound effect on susceptibility to chemotherapy
Crude indication of growth rate? frequency of mitoses
What is the first step for metastasis? loosening of intercellular junctions
In metastasis, what happens after loosening of intercellular junctions? attachment
In metastasis, what happens after attachment? degradation
In metastsis, what happens after degradation? migration
"soil and seed" theory different organs provide growth conditions optimized for certain cancers
Homing theory different organs have special abilities to attract cancer cells
Cartilage and skeletal muscle are rarely targets of metastasis, helping prove what theory? soil and seed
What are three ways tumors cause disease? tissue destruction, organ compression, obstruction
What are three more ways tumors cause disease? infection, anemia, soluble products
Created by: ges13