neoplasia II

is there a link between chronic inflammation and cancer? viruses?
yes
what tumors are associated with h. pylori?
stomach adenocarcinoma or B-cell lymphoma
what tumors are associated with EBV?
hodgkin lymphoma, nasopharyngeal cancer, non-hodgkin lymphoma, primary CNS lymphoma and burkitt’s lymphoma
what tumors are associated with HPV?
cervical, analgenital and oropharyngeal carcinomas
what tumors are associated with hepatitis B or C?
hepatocellular carcinoma and NHL is associated only with hep C
what tumors are associated with HIV/AIDS?
non hodgkin lymphoma, kaposi sarcoma
what are prenepoplastic disorders associated with endometrial carcinomas?
hyperplasia or dysplasias
what is a prenepoplastic disorder associated with gastric carcinomas?
chronic atrophic gastritis
what is a prenepoplastic disorder associated with colon carcinomas?
ulcerative colitis
what is a prenepoplastic disorder associated with squamous cell carcinomas?
leukoplakia
what is a prenepoplastic disorder associated with colon cancer?
colonic adenomas
what is a change in mucosa of esophagus called? what causes this?
barrett’s esophagus which is a result of metaplasia (which is likely due to GERD)
what initially causes cancer?
non-lethal genetic damage that kills most cells, but surviving cells can become neoplastic and whose clones can give rise to tumor cells. problems with protooncogenes, antioncogenes, apoptosis genes, and DNA repair genes can occur simlutaneously or independently of non-lethal genetic damage leading to carcinogenesis (a multistep process)
what are three common gene types that when mutated, lead to cancer?
activation of growth-promoting genes, alteration of apoptosis regulation genes, and inactivation of cancer suppressor genes
what does heterogeneity mean in the context of a developing malignant tumor?
when neoplasias develop heterogeneity, this means a whole population of cells with different abilities to divide, to multiply, to metastasize develop and many of which can be aggressive
what are oncogenes?
these encode oncoproteins which are devoid of regulatory elements, examples include: GFs, signal transduction proteins, nuclear regulatory proteins, cyclins
what gene, if overexpressed, is associated with PDGF causing an astrocytoma?
sis
what gene, if overexpressed, is associated with FGF causing an osteosarcoma?
hst-1
what gene, if overexpressed, is associated with FGF causing stomach/bladder/breast carcinomas?
Int-2
what gene, if overexpressed, is associated with EGF receptors causing a glioma?
erb B-1
what gene, if amplified, is associated with EGF receptors causing breast/ovarian/gastric cancer?
erb B-2
what gene, if subject to a point mutation, is associated with medullary carcinomas of the thyroid?
ret (a growth factor)
what might point mutations in the gene for ras, a signal transduction protein associated with GTP binding lead to?
various carcinomas
what might translocation of the gene for abl, a tyrosine kinase signal transduction protein, lead to?
leukemias (CML, ALL)
what does the myc gene encode? what happens if there is a translocation involving it?
myc encodes transcriptional activators and a translocation involving it can lead to burkitt’s lymphoma – which is linked to EBV and HIV. it is very fast growing; characterized by a “starry sky appearance” microscopically, w/ the sky being the lymphocytes – quickly proliferating lymphocytes, stars are macrophages which destroy dying and dead lymphocytes
what cancers might result from amplification of N-myc, a gene that encodes transcriptional activators?
neuroblastomas and small cell cancer of the lung
if there is an amplification in the gene for cyclin D, what cancers may result?
breast CA, esphageal CA, and some lymphomas
mutations in rb (a cancer suppressor gene) can lead to what kinds of cancer?
increased frequency of retinoblastoma
mutations in p53 (a cancer suppressor gene) can lead to what kinds of cancer?
colon, breast, lung and some sarcomas
mutations in WT (a cancer suppressor gene) can lead to what kind of tumor?
wilm’s tumor
mutations in EWS (a cancer suppressor gene) can lead to what kind of tumor?
ewing’s sarcoma
mutations in brca-1 & 2 (a cancer suppressor gene) can lead to what kinds of cancer?
breast cancer
mutations in DCC (a cancer suppressor gene) can lead to what kinds of cancer?
colon and gastric cancer
mutations in NF1 (a cancer suppressor gene) can lead to what kinds of cancer?
schwannoma, neurogenic sarcomas
mutations in NF2 (a cancer suppressor gene) can lead to what kinds of cancer?
schwannoma, meningiomas
mutations in APC (a cancer suppressor gene) can lead to what kinds of cancer?
colon, gastric, and pancreatic cancers
what 2 genes regulate apoptosis?
bcl-2 and p53
what do mutations in bcl-2 lead to?
overexpression of bcl-2 OVERprotects lymphomas from apoptosis, allowing them to survive longer than they are supposed to = follicular lymphomas
what does p53 do?
p53 triggers apoptosis
can some chemotherapeutic agents induce apotosis in cancer cells?
yes
what are 2 disorders associated with mutations in DNA repair genes?
hereditary nonpolyposis colon carcinoma and xeroderma pigmentosum (increased skin CA risk)
what are 2 examples of balanced chromosomal translocations that result in specific cancers?
CML results from 9->22 (philadelphia chromosome) and burkitt’s lymphoma results from 8->14 (associated with the myc protein, EBV and starry sky appearance)
what kinds of tumors are more commonly caused by chromocomal deletions?
nonhematopoietic (not arising from bone marrow elements) tumors such as retinoblastoma (chr 13)
what kind of cancer is associated with overamplification?
breast CA is associated with over amplification of Erb B-2
what are some things that influnence cell growth?
cell kinetics, angiogenesis, and tumor progression/heterogeneity
what are kinetics of tumor cell growth comprised of?
the doubling time of tumor cells (tumor cells are triggered into the cell cycle more readily), the growth fraction (the proportion of cells in the replicative pool & can divide), and cell production & loss (how much cell production exceeds loss)
what does bcl-2 do?
induce cell accumulation
what does bax do?
produces apoptosis (bax can be upregulated by p53)
what size can tumors not grow past w/out being vascularized?
1-2 mm
what growth factors powerfully stimulate tumor angiogenesis?
FGF, VEGF
can angiogenesis aid in tumor metastatis?
yes
what are the steps of metastasis?
invade ECM, detach from primary tumor, attach to matrix, degrade matrix, disseminate through vasculature, embolize w/WBC or travel solo
what are direct and indirectly acting chemical carcinogens?
direct-acting agents cause cancer and do not require metabolic conversion. indirect acting agents require conversion (aromatic hydrocarbons, cigarette smoke, aromatic amines/azodyes). both will result in gene mutations
what are some examples of radiation carcinogenesis?
UV rays can cause melanoma, BCC (not likely to metastasize), & SCC due to chromosome breakage, translocation and point mutations
what are some examples of virus induced cancer?
what cancers are associated with HSV?
kaposi’s (HHV-8), primary effusion lymphoma
what has RNA oncogenic virus been linked to?
human T cell leukemia virus has been linked to leukemia…duh
can cancer can be considered a STD by true definition?
yes
exposure to what does malignant mesolelioma have a strong association with?
asbestos exposure
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