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53 Cards in this Set
- Front
- Back
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what pathway is conserved in all eukaryotes and regulated by BRAF? what does this do? |
MAPK/ERK singnal transucer between outside and nucleus |
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what is the outcome of MAPK/ERK activation? what is the most potent activator of MAPK? |
cell differentiaion proliferation, growth and apoptosis BRAF |
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what does activation of ERK1/2 cause? what does inhibition of it cause? |
cell cycle arrest tumorigenesis |
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what is the affect of the mutation in BRAK V600E |
increase activation of MEK/ERK and activation without extrenal stimuli |
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how do melanocytes activate ERK1/2? what does activation of this cause? what is the ckd inhibitor in melanocytes? |
adhesion to the extracellular matric progress thru G1 and S phase and increase in cyclin and decrease cylin kinase inhibitors p27kip1 |
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what protien usually activates BRAF? what can early tumor stages be treated with alone? when more advanced stages? what is important step to determining BRAF mutation sensitivity? |
RAS BRAF inhibition alone blocking ERK and Pi3K pathways genotyping the tumor |
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define hypertrophy? define hyperplasia? dysplasia? neoplasia? |
increase in cell size increase in number of cells abnormal growth which disrupts tissue organization abnormal growth in which cells proliferate in an uncontrolled manner |
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how does a carcinogen work? how does HPV cause cancer? |
alters genetic structure encodes genome to render p53 and Rb, two tumor supperssor genese, inactive |
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what is a protooncogene? what is an oncogene? |
a normal gene that can cause cancer if mutated, can become an oncogene, does no harm by itself an abnormal gene that causes normal cells to become cancerous |
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what are the tumor suppressor genes? what is a mutagen? define autophagy? |
p53, reinoblastoma, BRAC1, BRAC2 increases frequency of DNA mutation in an organism self digestion by a cell through the action of enzymes originating within the same cell |
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define initation? promotion conversion and progression? |
exposure to carcinogenic substance to cause dna damage exposure to factors that favor growth of mutated cells over normal cells, does not create more mutations ..ex hormones genetic changes causing increased cell proliferation usually need mutiple initation invents to lead into conversion and progression |
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where do sarcoma cancers origninate from? what enzyme proofreads DNA? what are the phases of the cell cycle and what happens in each? |
supporting tissues like bone, cartilage, and muscle
DNA polymerase G1 growth S dna synthesis G2 duplicate chromosomes Mitosis |
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what is the longest stage of the cell cycle? what promotes the advancement to the next phase of the cell cycle? when do these exhibit protein kinase activity? |
G1 is 8 to 10 hours cyclin dependent kinases (CKDs) only when bound to a cyclin |
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what does a cdk cyclin complex do? what happens to the concentrations of cyclins at a stop point in the cell cycle? what do growth factors cause? |
phosphorylates specific target proteins essential for progression of cell cycle decline causes cells to divide |
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when in the cell cycle is the restriction point? what allows you to get past it? |
between G1 and the S Phase growth factors that increase cdk-cyclins that phosphorylate Rb protein |
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what is the function of Rb? what is E2F? how is it normally found? |
it is a tumor suppressor and is inactive when phosphorylated a transcription factor that gets a cell thru the S phase in its dephosphorylated form bound to Rb, prevents it from activation of transcription |
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what is the function of ubiquitin? what attaches the ubiquitin to the target protein? |
directs them to the proteasome for destruction ubiquitin ligase |
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what is the function of p53? what two events happens when p53 is activated? |
tumor suppressor that stops the cell cycle until dna repair or triggers apoptosis, its the guardian of the genome binds dna and codes fro p21 a cdk inhibitor, which prevents phosphorlyation of RB activates genes coding for apoptosis, makes a protein called Puma which blocks action of bcl2 |
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what proteins are utilized if there is a double strand break in DNA? what can a dysfunctional mitotic spindle checkpoint cause? what does the check here ensure? |
BRCA1 and 2 missegregation of chromosomes all chromosomes are attached to mitotic spindle |
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what proteins are involved in the seperation of chromosomes during anaphase? how is apc inhibited? |
anaphase promoting complex activates seperase which degrades cohesin proteins that hold duplicated chromosomes together mad and bub complex and bind cdc 20 which then binds and inhibits APC |
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what are the types of genetic alterations? |
point mutations, translocatioins, amplifications, deletions |
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what are the 2 ways that apoptosis can be activated? |
extrinsic pathway- extrenal signals bind the death receptor which triggers the caspase cascade intrinsic pathway- damaged dna triggers accumulation of p53 which stimulates production of death promoting proteins which causes the release of mitochondrial proteins which activates caspase cascade |
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what do proapoptotic proteins do? what are the names of these pro? what are the antiapoptotic proteins? |
inhibit the antiapoptotic proteins Bax and Bak bcl2 and bcl xl |
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how does the caspase cause cell death? what are the two major apoptotic targets for drugs? |
destruction f cytoskeletal proteins and indirect destruction of dna death receptors and the antiapoptotic protein bcl2 (want to down regulate it) |
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what is the main difference between apoptosis and necrosis? |
necrosis causes inflammation and is characterized by swelling, rupture, and spreading to surrounding tissues |
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what components activate angiogenesis? inhibit angiogenesis? |
VEGF and angiogenin prolactin and endostatin |
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how does VEGF work? |
binds VEGF recepto which causes endothelial cell division, endothelial cell migration, enhaced cell survival, and moblization or endothelial progenitor cells from bone marrow |
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define metastasis how to cancer cells travel in the body? how do they get into the transporting device? |
relocation of primary tumor cells and their subsequent proliferation at a distant site in the body blood or lymphatics adhere to the basal lamina and degrade the ecm, do the same thing to get out of the blood system |
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what is intravasation? what is extravastion? arrest? |
cancer cells passing through the basal membrane into a blood vessel moving the opposite of above in a particular site |
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whats the difference between a mutagen and a carcinogen? |
mutagen increases mutations carcinogen causes dna damage |
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what enzymes have remove free radicals? what ways do tumors avoid the immune system? |
superoxide dismutase and glutathione kill t cells and make a protective shield |
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what is chemoprevention? what medications are very non selective for cancer? |
using specific agents to block, delay, or reverse carcinogenic process nitrogen mustards and antimetabolites |
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what are the tyrosine kinase inhibitors and there targets? what drug inhbits the BRAF V600E mutation? what is this class of drugs? |
dasatinib, imatinib- BCR-ABL Erlotinib- EGFR vemurafenib raf kinase inhibitor |
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what do kinase inbhitor drugs end with? what are the main drug targets for cancer? which of these is the intracellular kinase? |
nib RAS and RAF and ABL BCR ABL BCR |
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what is HER-2? does it have a ligand? what does it bind do? what is the affect of this dimerization? what upregulates her2? |
a membrane protein no ligand but dimerizes with EGFR her2 is activated by egfr which leads to the transcription of breast ca genes estrogen |
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how do tyrosine kinase inhibitors work? what can over activity of the tyrosine kinase cause? what two ways can tyrosine kinases be activated? |
use ATP to phosphorylate tyrosine residues on target proteins, this leads to cell proliferation enhance cancer progression activated by growth factors or mutations |
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how do the tyrosine kinase inhibitors work? what is a non receptor tyrosine kinase? |
compete for ATP, which prevents growth signaling BCR-ABL |
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what happens once epidermal growth factor receptor is activated? what are the ways RAS proteins attach to the cell membrane? why are RAS proteins a target in the first place? |
dimerizes and phosphrylates tyrosine residues leading to signal transduction franeslyation or geranlygeranylation cause cell growth and cell division |
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if K RAS is mutated, what drugs become useless? does the absence of a kras predict the response of a EGFR inhibitor? what cancers are associated with K RAS mutations? |
anything above the transduction pathway, in this case EGFR inhibitors not a strong predictor of beneficial response at all colorectal and pancreatic |
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when do most KRAS mutations occur? what are the MMPs? |
are somatic and happen after birth proteins that degrade the ECM and can lead to metastasis |
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what is the standard to test for K RAS mutations? how would you do it? |
there is none extract ran from biopsy, PCR, sequence rna, then dna sequence |
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what is CaaX? what adds the hydrocarbon group? what does caax protease do? whats happens next? |
C is the cterminus of the target protein geranlygeranyltransferase or farneslytransferase adds hydrocarbon to the already attached caax removes the aax part methyltransferase adds methyl group to where aax was removed, then goes to membrane where it can be activated by EGFR |
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how do we combat the mutated K RAS? how do these drugs fight it? |
HMG CoA reductase inhibitors, bisphosphonates, and other interference with the mevalonate pathway inhibit the formation of FDD and GGPP |
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how do the bisphophonates fight kras mutation? what is the ultimate goal of all of these drugs? |
inhibit farnesyl PP synthase which decreases FPP and GPP of kras, inducing apoptosis usually not used in therapy PREVENT THE PRENYLATION OF KRAS |
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what does expression of ABL gene create? what is the philadelphia chromosome? typically how is ABL found? |
tyrosine kinase which activates RAS ABL gene fuses with BCR gene forming an oncogene that is reistant to apoptosis and leads to the proliferation of hematopoietic stem cells (creates a fusion protein) with a repessive gene infront of it |
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what drugs inhibit the EGFR tyrosine kinase? what drugs inhibit the abl bcr? |
erlotinib imatinib and dasatinib |
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what type of cancer is a BRAF mutation common in? what is the most common mutation? |
metastatic melanoma BRAF V600E, valine is mutated to glutamate, causing BRAF to be highly active |
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how does vismodegib work? what are the antimetabolites? |
supresses SHH signaling by interfering with smoothened folate analogs, purine and pyrimidine analogs |
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what are the alkylating agents? what drug is the DNA hypomthelator? |
nitrogen mustards, nitrosureas, platinum analogues (technically not alkylating) azacitidine |
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what is the function of toposiomerase? whats the difference between nucleoSide and nucleoTide? is uracil in DNA or RNA? |
untagles and unwinds DNA and then reseals dna together nusleoside lacks the phosphate while nucleotides have a base, sugar, and a phosphate RNA replaces thymine |
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what does methotrexate mimic? what does this inhibit? |
folic acid dihydrofolate reductase to keep tetrahydrofolate in its reduced form and prevents the formation of thymidine |
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what is the function of glucarpidase? how quick does it work? how does leucovorin work? what is the other name for leucovorin? |
destroys methotrexate, removes 96% in 15 minutes works beyond the dihydrofolate reducatse, is convereted into THF and resumes DNA synthesis, protects the healthy cells folinic acid |
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how does flurouracil work? |
inhbits thymidylate synthase, it competes with with dUMP which decreases dTMP leading to cell death |
