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42 Cards in this Set
- Front
- Back
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What is an epigenetic change in regard to CA?
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tumor suppresor gene is inactivated by methylation of promoter sequence
ex. p14ARF in colon and stomach CA BRCA1 in breast CA VHL in renal cell carcinoma MLH1 in colon CA |
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What is molecular profiling?
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examination of RNA expression in tumors by DNA microarray analysis where cDNA from normal tissue is compared to cDNA of tumor cells. used to determine tx and predict tumor behavior.
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What is significant about the genetic alterations required to activate oncogenes/inactivate tumor suppressor genes that will lead to CA?
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there must be MULTIPLE genetic alterations because combinations of mutated oncogenes are required to transform cells
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What is the multistep process of carcinogenesis that occurs with colorectal CA?
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1. normal
2. loss of mutation of APC -> dysplastic foci, early adenoma 3. mutation os RAS -> intermediate adenoma 4. loss of tumor suppressor -> late adenoma 5. loss of p53 gene -> carcinoma |
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What's the difference between carcinoma and adenoma?
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carcinoma = cancer
adenoma = benign |
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What is the difference between gatekeeper genes are caretaker genes?
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gatekeeper - regulate entry of cell into tumorigenic path like tumor suppressor genes
caretaker - affect genomic instability like repair genes, but do not control growth |
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What is tumor progression?
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increasing aggressiveness of a tumor over time results from increased mutation/heterogeneity -> more adept CA cells
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How many known mammary carcinogens have been isolated from second hand smoke?
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20!
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What is the ECOG performance status scale?
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0 - no life changes as a result of CA
1 - restricted in very strenuous activity 2 - capable of self-care, but not work, out of bed > 50% of waking hours 3 - capable of limited self-care, in bed > 50% of waking hours 4 - no self-care, confined to bed 5 - dead |
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Listed in order of highest exposure, what are common radiation exposures that could eventually produce CA?
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highest
1. annual radon in home 2. annual diagnostic radiology 3. annual natural radioactivity in the body 4. single mammogram 5. annual terrestrial radioactivity 6. annual cosmic radioactivity 7. single chest x-ray 8. annual nuclear power station exposure lowest |
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How to chemical initiators and promoters cause CA?
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initiators cause permanent irreversible DNA damage. when those cells come in contact with come in contact with promoters, they will selectively expand. normal cells will not react with promoters.
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What is the difference between direct and indirect acting chemical carcinogens?
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direct - bind covalently to DNA nucleotides (alkylating or acylating) -> carcinogenic
indirect - require metabolic conversion to be carcinogenic |
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What are procarcinogens?
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indirect acting carcinognes that are mostly metabolized by cytochrome p-450 dependent mono-oxygenases
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What is the Ames Test?
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a screening test that usually indicates a carcinogenic chemical by observing it's mutagenic capability in Salmonella typhimurium
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What is molecular fingerprinting of CA?
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identifying a carcinogen based on the specific DNA base sites of reaction
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How does UV radiation cause skin CA?
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BCC and SCC occur when UVB causes pyrimidine dimers in DNA that exceed the repair capacity of the NER
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What are the first and second most frequent cancers caused by ionizing radiation?
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1. leukemia
2. thyroid CA |
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What are oncogenic DNA viruses and what are 4 examples?
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oncogenic DNA viruses integrate into the host cell genome -> mutation
1. HPV 2. EBV 3. HBV 4. HHV-8 |
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What three presentations (due to different HPV types) do HPV display?
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1. benign warts
2. genital warts 3. squamous dysplasia, squamous cacinoma, invasive squamous cell carcinoma of the cervix |
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What is the difference between cancerous HPV and non-cancerous HPV?
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cancerous - HPV is integrated into the genome
non-cancerous - HPV is episomal |
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What other role does HPV play in CA causation?
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initiator
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What 5 medical conditions does Epstein-Barr Virus cause?
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1. burkitt lymphoma
2. B-cell lymphoma 3. nasopharyngeal carcinoma 4. hodgkin lymphoma 5. infectious mononucleosis |
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What is the pathogenesis of Hepatitis B virus caused hepatocellular carcinoma?
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1. viral DNA is integrated into host genome
2. damaged liver cells promote regenerative hyperplasia 3. increased number of cells increases probability of mutation 4. HBV encodes HBx proteins which promotes further growth |
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What is Kaposi sarcoma?
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HHV-8 caused skin CA. looks like a cheese stick.
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What are the two oncogenic RNA viruses?
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1. Hep C virus
2. Human T-cell leukemia virus 1 (HTLV-1) |
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What types of cancer does HCV cause?
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hepatocellular carcinoma
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What gene is partly responsible for HTLV-1 caused leukemia?
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TAX gene
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What bacterial agent can cause gastric lymphoma and gastric carcinoma?
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H. pylori
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In the case of gastric lymphoma caused by H. pylori, what tissue is involved and what is the tx?
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chronic H. pylori infections of MALT can be treated by treating the bacterial infection. this leads to regression.
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What is special about some strains of H. pylori that cause gastric carcinoma?
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CagA protein is produced by some strains, is inject into host cell and VacA toxin -> chronic gastritis -> gastric atrophy -> intestinal metaplasia -> dysplasia -> carcinoma
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What is the difference between tumor specific antigens and tumor associated antigens?
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tumor specific are only on tumor cells
tumor associated are on tumor and some normal cells |
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What is the main antitumor effector immune cells?
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Cytotoxic T cells
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What are other anti-tumor effector cells other than CTL?
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NK cells
macrophages antibodies |
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How do tumor cells avoid immune surveillance?
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1. loss of MHC-I to evade CTL
2. no co-stimulatory molecules for T cell complete sensitization 3. active immunosuppresion by expression of TGF-B 4. antigen masking by glycocalyx molecules 5. apoptosis of T cells by tumors expressing Fas ligand |
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How do tumors effect hormonal equilibrium?
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tumors can produce hormones, themselves, or they can destroy glands that produce hormones to reduce needed hormone production
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What is Cancer Cachexia?
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wasting syndrome caused by cytokines e.g. TNF and soluble factors produced by tumor and how the body reacts to the tumor
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What is paraneoplastic syndrome?
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may be first indication of cancer, mimicking metastatic disease. this syndrome will be a result of the presence of the tumor and it's release of hormones and cytokines to systemic circulation
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What types of paraneoplastic syndromes are there?
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endocrinopathies
nerve and muscle syndromes skin disorders bone, joint, soft tissue changes vascular and hematologic conditions |
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What is an example of a paraneoplastic syndrome?
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Cushing syndrome which is an endocrinopathy caused by ACTH or ACTH-like substance that produces small cell carcinoma of the lung
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What is SIADH?
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endocrinopathy paraneoplastic syndrome cuased by ADH or atrial natriuretic hormones that cause small cell carcinoma of the lung and intracranial tumors
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What is an endocrinopathy paraneoplasia syndrome that is caused by parathyroid hormone-related protein, TGF-alpha, TNF, and IL-1 that causes squamous cell carcinoma of the lung?
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hypercalcemia
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What is hypoglycemia?
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endocrinopathy caused by insulin or insulin-like proteins that can cause fibrosarcoma and hepatocellular sarcinoma
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