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Terms in this set (215)
Growth signal autonomy, evasion of growth inhibitory signal, evasion of apoptosis, unlimited replicative potential, angiogenesis, invasion and metastasis, impairment of differentiation, loss of dna repair systemHallmarks of cancerCell to cell & cell to ECM interactionTissue invasion & metastasis -> loss of ...Infiltration, invasion, destructionGrowth of cancer is usually accompanied by progressive ..., ..., ... of surrounding tissueBasement membraneCarcinoma in situ : ... ๋๊ธฐ ์ Escape from parent tissue, travel through circulation, colonization of remote site3 Cellular changes required for metastasisInvasiveness causes entry into vesselEscape from parent tissue : ...Survival in circulation, arrest in capillary, exit into remote tissueTravel through circulation
1. ...
2. ...
3. ...Survival in foreign tissue, initial growth in foreign tissue, persistence of growthColonization of remote site
1. ...
2. ...
3 ...Protease, uPA, procollagenase, PAI, TIMPSecreted ... by tumor generate pathway through basement membrane in metastasis.
endothelial cells increase their secretion of ... and ..., and decrease secretion of ... and ....Leukemia initiating clone, leukemic stem cellHematopoietic cell์์ leukemia๊ฐ ๋ฐ์ํ๋ ์์๋?
Hematopoietic stem cell -> ... -> ... -> leukemiaNormal, aging, normal, cancerDNA damage in non replicating cell -> DNA repair -> ...
DNA damage in non replicating cell -> no DNA repair -> ...
DNA damage in replicating cell -> DNA repair -> ...
DNA damage in replicating cell -> no DNA repair -> ...Base excision repair, nucleotide excision repair, recombinational repair, mismatch repair, direct reversal repairFive types of DNA repair systemRecombinational repairBRCA1 gene์ ์ด๋ค repair process์ ์ํด ๊ณ ์ณ์ง๋์ง?ATM kinaseAtaxia telangiectasia is an inherited syndrome whereby patients have a mutation in the ...Ataxia telangiectasiaPatients are sensitive to X-rays and have an increased risk of lymphomaBRCA1, BRCA2The first breast cancer gene defects to be found were ...DNA repairp53 is central in orchestration of ...Growth signal autonomy, evasion of growth inhibitory signal, unlimited replicative potentialHallmark of cancer ์ค increased proliferation์ ๊ด์ฌํ๋ ๊ฑฐ?Unlimited replicative potentialHallmark of cancer ์ค increased self renewal์ ๊ด์ฌํ๋ ๊ฑฐ?Loss of DNA repair systemHallmark of cacner ์ค Genomic instability์ ๊ด์ฌํ๋ ๊ฑฐ?Evasion of apoptosisHallmark of cancer ์ค increased cell survival์ ๊ด์ฌํ๋ ๊ฑฐ?OncogenesMutated genes that cause cancerMultiple mutation... theory is supported by the fact that the incidence of contracting most cancers increases steadily with agemyc, rasDMulti-step model for cancer development๋ฅผ ์ฆ๋ช
ํ๊ธฐ ์ํ ์คํ์์ ์ฌ์ฉํ ๋ ๊ฐ์ง์ oncogene?Short, change in cell, malignant transformation, long, repeated exposure, express transformed phenotype, develop into tumorTumor initiation is depicted as a ... interval during which can induce a ... which a carcinogenic agent predisposes it to ...
Tumor promotion is illustrated as a ... time interval during which ... to an active agent can induce the initiated cell to ...
Tumor progression is depicted as the time during which transformed cell .... .Tumor initiation, initiated cell, tumor promotion, dysplasia, tumor progression, adenoma, carcinoma, metastasis, metastic tumorNormal cell -(...)-> ... -(...)-> ... -(...)-> ... -> ... -(...)-> ...Initiating mutation, clonalAll of cancer cells in patient arise from single cell that contains an accumulation of ...; in other words, the development of cancer is ...Ames testtest for mutagenecityChemical carcinogen, radiation, viral infectionExogenous carcinogenExposure to carcinogen, life styleGreat majority of cancer development are caused by external factors including exposure to ... and ...Polycyclic aromatic hydrocarbons(PAHs), aromatic amines, nitrosamine and nitrosamide, alkylating agentFour major classes of genotoxic chemical carcinogenRadiationPhysical carcinogenTumor virusBiologic carcinogenBacteria, parasiteBiological carcinogensTumor promotorNongenotoxic carcinogen usually act as ...Chemical carcinogen, become active after they are metabolizedIndirect carcinogen ?Cytochrome p450, activation of carcinogen, ultimate carcinogenA family of enzymes, called the ... enzyme, is involved in the metabolism of chemicals in the liver and is important in the ... to ...Cyp1a1, 50-fold in human lung tissue, delivery of varying doses of ultimate carcinogen, smokersExpression of one of the p450 enzyme called ... can vary ... and may be responsible for the ... among ...Electrophilic, nucleophilic site, DNAGenotoxic chemical carcinogens are ... form react with ... of ...DNA adducta segment of DNA bound to a cancer-causing chemicalBenzopyrene diol epoxide, nucleophiles on DNA, between DNA base pair1. ์ด๋ฆ
2. ํ์ดํ ์น ๋ถ๋ถ์ ๋ญ๋ ๋ฐ์?
3. 4๊ฐ์ ring์ ์ด๋์ ์์น?Aromatic aminesAminobiphenyl์ ๋ฌด์์ ์์?N(7)-MeG, O(6)-MeGNitrosamine์์ ultimate carcinogen์ด ๋ง๋ค์ด์ง๋ฉด?Pseudo watson-crick pair, wobble pair, pO(6)-MeG์ ์ํด ๋ง๋ค์ด์ง ์ ์๋ pair? ๋ ์ค ๋ฌธ์ ์๋ ๊ฒ์ ์ฒซ ๊ธ์?Intrastrand linking, cross linkngAs genotoxic chemical carcinogen, bifunctional alkylating agent can cause ... and ...IonizingX-rays, ฮณ rays = ... radiationIonization of atoms, interaction with water molecule, radiolysis, ROSIonizing radiation can damage DNA directly by causing ... comprising DNA, or indirectly by ... (process known as ...) to generate ...Guanine, 8-oxoguanineBy ionizing radiation, ... is transversed to ...Ionizing radiationDouble strand break๋ ionizing radiation vs non ionizing radiation ์ค ๋ญ์ ์ํ ๊ฒ?Non ionizing radiationKink by thymine dimer๋ ionizing radiation vs non ionizing radiation ์ค ๋ญ์ ์ํ ๊ฑฐ?UVBMost effective carcinogenAging of skin, pigmentation, sunburn, skin cancer, absorbed in ozone layerUVA -> ..., ...
UVB -> ..., ...
UVC -> ...UVB, CPD, 6-4 ppsAdjacent T bases๋ ...์ ์ํด ...์ ...๋ก ๋๋๋ค.Inhibition of tumor suppression, viral oncogenes and insertional activationDNA tumor virus์ ์ญํ :
RNA tumor virus์ ์ญํ :Hepatic cancer, cervical cancer, burkitt's lymphoma and hodgkin's lymphomaDNA virus์ ๊ด๋ จ๋ tumor
HBV ->
HPV ->
EBV ->Rb, p53Viral protein์ด ๊ฒฐํฉํ๋ tumor suppressor gene?pRB, E2F, pRB, p53(A) ...๋ ...์ด cell cycle์ ์งํ์ํค์ง ๋ชปํ๋๋ก ํ๋ค
(B) DNA tumor virus๋ ...์ ๊ฒฐํฉํ์ฌ ์๋ ์์ฉ์ ํ์ง ๋ชปํ๊ฒ ๋์ด cell cycle progression ์ํจ๋ค
(C) DNA tumor virus๊ฐ ...์ ๋ถ์ผ๋ฉด cell cycle arrest ์ํจ๋คCarry oncogene, alter transcriptional regulationAcute transforming retrovirus๋ ... , slow transforming retrovirus๋ ... .Kidnapping mutated version of normal cellular gene, randomly inserting next to protooncogene, activating expressionRetroviruses cause cancer by ... .
Retroviruses also cause cancer by ..., thus ...Insertional mutagenesis... provide a powerful tool to find new oncogeneMalaria, EPV... (caused by parasite) is associated with burkitt's lymphoma in Africa, especially when present in combination with ...Oxidative respiration, lipid peroxidation, 8-oxoguanineTwo processes of normal cell metabolism ( ... and ... ) produce ROS to produce ...Ionizing radiation, ROS8-oxoguanine์ด ์๊ธฐ๋ ๊ธฐ์ ๋๊ฐ์ง?Deamination, hydrolysis, glycosidic bond, abasic siteSpontaneous chemical reaction
- ... of cytosine to form uracil
- ... of ... between base and deoxyribose -> producing ...Translesion synthesis, low fidelity polymerasesAP site๊ฐ tolerance ์๊ธฐ๋ฉด -> ... -> employs ...Environment, reproductive life, diet, smokingFour influential factors that play an important role in carcinogenesisNot having children, delaying first childbirth, not breastfeeding, early menarche, late menopauseIncrease exposure to endogenous *estrogen* (..., ..., ..., ..., ...) are suspected of increasing liftime risk for developing breast cancerDevelop new spontaneous mutation, stimulate division of existing mutant uterine cellEstrogen action on uterusBreast cancer, blood clot, uterine cancerBad effect of estrogen replacement during menopauseInvasive breast cancer, blood clot, heart attack, strokeBad effect of estrogen+progesterone replacement during menopausetranscription factor and regulation, chromatin structure, epigenetic regulationRegulation of gene expressionDNA sequence, gene activityEpigenetic modification do not change the ..., but affect ... .DNA methylation, histone modification, RNA interferenceEpigenetic modification on DNA & Histonecytosine, CpG, DNMT, relaxed, on, DNDMDNA methylation : ... at ... sites
- hypomethylation -> ... chromatin -> turn ... transcription
- hypermethylation -> ... chromatin -> turn ... transcriptionCpG island, promoter region, normal, occur, repetitive sequence, promoter region of repressed genesCpG cluseter, called ... are located in the ... of 50% of human genes.
CpG island are not methylated in ... tissue and transcription may ...
Methylated cytosines in CpG islands are found mainly ... and ...1, hemimethylated, fully methlated, replication, inheritableDNMT ... : ... DNA -> ... DNA (during DNA ...)
this mechanisms allows methylation patterns to be ...De novoDNMT 3a, 3b : mainly involved in ... methyltransferase activityDeaminate, C-T transitionMethylcytosine ... spontaneously and results in ...Methylation, acetylationHistone์ ... ๋ condense form์, ...๋ relaxed form์ ์ ๋ํ๋คhistone acetyltransferase, relax, transcriptional elongation, histone deacetyltransferase, chromatin compaction, packaging, repression(Enzyme) ... acetylate specific histone lysines. It ... chromatin folding and correlated with enhanced ... .
... removes acetyl group and stabilize ... and higher level ... -> ... of transcriptionDocking, recruitment, repulsionAcetylation acts as a ... signal for the ... or ... of chromatin modifying factorRbModification of chromatin by ... ; this protein exert its effect by recruiting HDAC.RNA induced silencing complex, degradedFurther processing of miRNA biogenesis leads to incorporation of one strand miRNA into ... and guides it to target mRNA, while another strand ...Hypermethylation... in the promoter regions of tumor suppressor genes is a major event in the origin of many cancer.Oncogene, tumor suppressormiRNA knock down strategy to ... miRNA -> cancer
miRNA replacement strategy to ... miRNA -> cancerTomato, apple, citrusDNA methylation inhibition์๋ง ๊ด์ฌํ๋ ์์?Cashew nuts, grapes, garlicHistone modification์๋ง ๊ด์ฌํ๋ ์์?P53Soybean serves to increase activity of ...ProtooncogeneNormal gene that encodes a protein involved in stimulation of cell growth and in inhibition of apoptosisOncogeneMutated proto-oncogenes that produces abnormalities in the cell growth and apoptosisTumor suppressor geneNormal gene that encodes a protein involved in suppression of cell growth and in induction of apoptosisCaspid protein, reverse transcriptase, envelope proteinViral RNA genome์๋ gag, pol, env๊ฐ ์๋ค. ๊ฐ๊ฐ ์ด๋ค protein์ encodingํ ๊น?Envelope, Reverse transcriptase, RNA/DNA, RNase H, DNA/DNA, integrase, integrated DNA, transcription, translation, caspid, envelope, reverse transcriptase, assemblyLife cycle of Retrovirus
1. Entry into cell and loss of ...
2. RNA -(...)-> ... -(...)-> ... -(...)-> ...
3. ...
4. ... -> ... protein, ... protein, ...
5. ...DNA RepairCaretaker gene์ด ๊ด์ฌํ๋ ๊ฒ์?Gain, dominant, one, somatic alteredoncogene
- ... of function mutation
- ... trait
- ... mutation is required for cancer
- ... mutation
- ... gene involved in positive regulation of cell proliferationDominant negative effectIn p53, one mutation cause ...Loss, recessive, haploinsufficiency, two, germ line&somatic, wild typeTumor suppressor gene
- ... of function mutation
- ... trait or ...
- generally ... mutation is required for cancer
- ... mutation
- ... gene involved in positive regulation of cell proliferationCaretaker geneDominant negativeํ๊ฒ ์ ์ ๋๋ gene?Growth factor, growth factor receptor, intracellular transducer, transcription factor, anti-apoptosis protein & apoptosis, cell cycle control protein, DNA repair proteinTypes of proteins participating in controlling cell growthRas, Raf, MycmitogensTgfฮฒ, p53, RbAnti mitogensUnfavorable extracellular environment, damaged DNAG1 checkpointIncompletely replicated DNAS checkpointDamage or incompletely replicated DNAG2 checkpointchromosome improperly attached to mitotic spindle(chromosome misalignment)M checkpointD, 4/6, e, 2, a, 2, 2, b, 2Cell cycle regulation
- G1 phase : cyclin ... + CDK ...
- G1 phase after R protein : cyclin ... + CDK ...
- S phase : cyclin ... + CDK ... or CDC ...
- G2 phase : cyclin ... + CDC ...p15,16,18,19early G1 phase์ ๋ง๋ค์ด์ง๋ D-CDK4/6 complex์ inhibitor?p21, p27, p57ECDK2, ACDK2, ACDC2, BCDC2 inhibitorCyclin D1, p16, Rb, TGFฮฒ, TGFฮฒ, Smad2, Smad4mutation causing loss of cell cycle control
- passage from G1 to S phase : overexpression of ..., loss of ... function, loss of ... function
- loss of ... signaling contributes to abnormal cell proliferation and malignancy : ... receptor, ..., ...
-Mitochondrial, death receptorApoptosis pathway ; ... pathway and ... pathwayCell injury, Bcl-2, Bcl-2, bax, bak, bcl-2, bcl-x, cytochrome c, initiator caspases 9, executioner caspases 3Mitochondrial (intrinsic) pathway
1. ...
2. ... family sensors
3. ... family effectors (..., ...) (Iโ regulators : ..., ... )
4. Mitochondria
5. ... and other pro-apoptotic protein
6. ...
7. ...
8. Apoptosisreceptor, ligand, Fas, TNF receptor, adapter protein, initiator caspases 8, executioner caspases 3Death receptor (extrinsic) pathway
1. ... - ... interaction (..., ...)
2. ...
3. ...
4. ...
5. ApoptosisBid, bad, baxBcl-2 family ; pro-apoptoticP22 bid, p15 tBidInitiator caspase-8๋ inactiveํ ...๋ฅผ ๊ฑฐ์ณ activeํ ...๋ฅผ ํตํด ์์ฉํ๋ค.Bcl-x, apoptosis, survival, AktBad๋ ...์ ์์ฉ์ ๋ฐ์ผ๋ฉด pro-apoptoticํ ์ํ๋ฅผ ์ ์งํ๋ค. ์์ฉ์ด ์ฌ๋ผ์ง๋ฉด ...๋ฅผ ์ด๋ ์ ์๊ณ , 14-3-3 phosphorylation๋๋ฉด ...๋ฅผ ์ด๋๋ค. ์ด๋ฅผ ์กฐ์ ํ๋ ๊ฑด ... ์ด๋ค.PI3 kinasePIP2 -> PIP3phosphatase and tensin homologPIP3 -> PIP2AktSurvival factorPTENDeletion of (PI3 kinase/PTEN) is frequent occurence in human tumorPIP3, PTEN, PIP3PIP3 vs PIP2 ์ค cell progression์ ์ผ์ผํค๋ ๊ฑด ...
๋ฐ๋ผ์ tumor suppressor gene ์ญํ ์ ํ๋ ...๊ฐ depletion ๋์ด ...๊ฐ ์์ด๋ ๊ฒ์ด frequent occurence in human tumorsAbolish g1 checkpoint control, DNA tumor virus, human carcinogen, DNA repair system, chromosomal abnormality, telomeraseMutations affecting genome activity
1. Inactivating mutation in p53 ...
2. Protein encoded by ... can inhibit p53, Rb activity
3. ... cause inactivating mutation in p53 gene
4. Defect in ...
5. ... are common in human tumors
6. ... expression may contribute to immortalization of cancer cellsPoint mutation, deletion, coding, point mutation, deletion, regulatory, overexpression, gene amplification, insertional, viral integration, chromosomal translocation, fusion, novelActivation mechanism of proto-oncogene
1. ... and ... in ... sequence -> structural and functional change
2. ... and ... in ... sequence -> ...
3. ... : increase in gene dose and protein production
4. ... mutagenesis caused by ... -> aberrant expression
5. ... -> ... proteins with ... functionRas, codon 12, ras protooncogene, loss of GTPase activityPoint mutation/deletion in coding sequence
- ... : mutation in ... of ... result in the ...N-myc, Neuroblastoma, homogenous staining region, double minutesGene amplification
- ... gene amplification in ...
- amplified as expanded intrachromosomal ... or as extrachromosomal ...transposon, identify oncogeneInsertional mutagenesis caused by viral integration
- ... contains signal to truncate expression of an interrupted gene and then restart expression of second truncated gene -> this method has been used to ...Chimeric protein, 9, 22, philadelphia chromosome, CML, 15, 17, AML, insertional, 8, 14, burkitt's lymphomaTwo distinct mechanism of chromosomal translocation
1. ... formation
1) t(...;...) translocation ; ... -> ...
2) t(...;...) translocation -> ...
2. ... activation
- t(...;...) translocation -> ...Philadelphia chromosome, bcr-abl, chronic myelogenous leukemia, p210, tyrosine kinase, cell cycle progressiont(9;22) translocation ; ...
-> ... fusion protein in ...
resultant protein - ... : potent ... resulting in dramatic ...PML,RAR, retinoic acid, white blood cell, acute myelogenous leukemiat(15;17) translocation (... fusion protein) results in a mutant form of ... receptor that block ... differentiation, leading to ...Myc, enhancer, IgHt(8;14) translocation places ... gene expression under control of transcription controlling ... of ...amino acid side chain, phosphotyrosineSrc์์ SH3 binding site of ..., SH2 binding site of ... .Phosphotyrosine, sh2, tyrosine kinase, c terminal tail dephosphorylated, tyr 416 phophorylated, phosphorylated tyr 427, activeActivation mechanism of src
- inactive state : 527๋ฒ์งธ ์๋ฏธ๋
ธ์ฐ์ธ ...๊ฐ ... domain๊ณผ ๋ถ์ด ์๋ค.
- partially active : PDGF-R ๋ฑ Src activator๊ฐ ์ค๋ฉด pdgf receptor์ ... domain์ phosphotyrosine์ด ๋ถ์ด์ ...
- fully active : ...
inactive ์ํ์์๋ ...๊ฐ ์ค์ํ ์ญํ ์ ํ๋๋ฐ, v-src์๋ ์ด๊ฒ ์์ด์ ๊ณ์ ...Mutant form of receptor tyrosine kinaseProto oncogene์ด์๋ growth factor receptor์ ๋ฌ๋ฆฌ oncogene์ด ๋๋ฉด ...Tyrosine kinase activitymajority of oncogene derived from growth factor receptor : ...Dimer, ligand, ligand independent firingGFR๋ ...๋ฅผ ํ์ฑํด์ ... dependent firing์ ๋๋๋ฐ, mutation์ด ์๊ธฐ๋ฉด ...Point mutation, neu, deletion, ErbB1, translocation, with ETV6HER2 -(...)-> ...
EGF-R1 -(...)-> ...
PDGF receptor -(...)->Epo, erythropoietin proliferation, gp55, firing, erythroleukemia...๋ผ๊ณ ํ๋ erythropoietin์ growth factor receptor์ ๋ถ์ด์ ...์ ํ์ํ๋ฐ, viral oncoprotein ์ค์ ...๊ฐ ๊ตฌ์กฐ๊ฐ ์ ์ฌํ์ฌ receptor๊ฐ ๊ณ์ ... ํ๋ค. ๊ทธ ๊ฒฐ๊ณผ ...๊ฐ ์ด๋๋๋ค.Genital wart, cervical cancer, PDGF receptorhuman papillomavirus which causes ... and ..., produces a protein that triggers growth of cells via activation of ...Human papillomavirus, p53, apoptosis inhibitor, pRB, cell proliferation...๋ E6 & E7 protein์ releaseํ๋ค. E6 protein์ ...์ ๋ถ์ด ...๋ก ์์ฉํ๊ณ , E7 protein์ ...์ ๋ถ์ด ๊ทธ ์ญํ ์ ๋ฐฉํดํด์ ...์ ๊ฒฐ๊ณผ๋ก ์์ฉํ๋ค.RasMutations in ... gene are found in about 30% of human cancersguanine nucleotide exchange factor, gdp-GTP exchange, GTPase activating protein, dephosphorylationras proto-oncogene์ ...์ ์ํด ...๋๋ฉฐ activation ๋๊ณ , ...์ ์ํด ...๋๋ฉฐ inactivation ๋๋ค.Translocation of cytosolic Ras protein to cell membraneProcess essential to RAS activationGTPaseRas protooncogene๊ณผ๋ ๋ค๋ฅด๊ฒ ras oncogene์ ... enzyme์ ์์ฉ์ด ์ ์ผ์ด๋์ง ์์์ cancer๋ฅผ ์ ๋ฐํ๋คPoint mutationRas protooncogene์ ์ด๋ค mutation์ด ์ผ์ด๋์ผ oncogene์ด ๋ ๊น?DNA lesion, sensor protein, RAD/MRN complex, transducer, ATM and ATR kinase, effector, Chk2 and Chk1 kinaseDDR checkpoint pathway
... are detected by ... (ex. ...) and these signals are relayed via ... (ex. ...) to ... (ex. ...)Tumor suppressoR geneOften the 1st mutation in a developing cancerI๋ ๋ชจ๋ cell๋ค์ germline mutation์ ์ํ first hit์ ๊ธฐ๋ณธ์ ์ผ๋ก ๊ฐ์ง๊ณ ์๊ธฐ ๋๋ฌธ์, ์ด๋ค cell์ด๋ rb gene์ coding sequence์ ๋ฌธ์ ์ด๊ฑด epimutation์ ๋ฌธ์ ์ด๊ฑด loss of function์ ์ผ์ผํค๋ mutation์ด ์ผ์ด๋๋ฉด retinoblastoma๊ฐ ์๊ธด๋ค. S๋ ๊ฐ์ tissue์ ๊ฐ์ cell์ loss of function์ ์ผ์ผํค๋ mutation์ด ๋ ๋ฒ์ด๋ ์ผ์ด๋์ผ retinoblastoma๋ก developํ๊ธฐ ๋๋ฌธ์ ๊ทธ chance๊ฐ ์ค์ด๋ ๋ค.Two hit hypothesis
inherited retinoblastoma : ...
sporadic retinoblastoma : ...Loss of heterozygosityMutant heterozygote๋ mutant homozygote๊ฐ ๋๊ธฐ ์ ๋
์ฝ๋ค. ์ด์ ๋?Non disjunction, mitotic recombinationLoss of heterozygosity์ ๋ํ์ ์ธ ๋ ๊ฐ์ง ๊ธฐ์ ?Chromosome loss, deletion, unbalanced translocation, point mutationNondisjunction๊ณผ mitotic recombination์ ์ ์ธํ loss of heterozygosity์ ๊ธฐ์ 4๊ฐ์ง?Regulate level of ฮฒ catenin proteinAPC์ ์๋ ์ญํ : ... in cytosolMDM-2 protein stability, p53 stabilityP14art : regulate ... and hence ...Nf-1Ras-GTPase์ gene?Transcriptional factor of TGF-ฮฒSmad4?TSE-cad๋ oncogene or tumor suppressor?Dna mismatch repairMSH2, MLH1, PMS1, PMS2, MSH6์ ์ญํ ?Transcriptional cofactor, adaptor protein, gene expressionRb is a ... and ... that functions primarily as a regulator of ...E2F1, g1/s cell cycle transitionRb binds to a protein called ... . That protein initiates ... .Multiple p53 gene copiesElephants almost never get cancer thanks to ...Point mutation, DNA bindingMost of p53 mutations (95%) are ... in ... domainDna damage, ATM Kinase, ChK2, oncogene activation, p14arf, MDM2, cell stress, ATR, casein kinase IIUpstream factors of p53
... -> ... -> ... -> p53
... -> ... -I ... -> p53
... -> ... -> ... -> p53Cell cycle arrest, DNA repair, apoptosis, inhibition of angiogenesisp53 ์ผํ๊ฒฐ๊ณผ?Phosphorylation, ubiquitinationP53 activity is controlled by coupled ... & ... reactionATM, phosphorylate, MDM2, high p53 levelAfter DNA damage, upstream kinase (ex. ...) ... p53, disrupting ... binding and leading to ...Ubiquitination, lowMDM2๊ฐ ์์ ๋ถ์ผ๋ฉด p53์ (phosphorylation/ubiquitination) reaction์ด ์ผ์ด๋ p53 (high/low)์ํ๊ฐ ๋๋ค.Mdm2๋ p53์ target gene์ด์ฌ์ p53์ด stabilized๋๋ฉด high level of MDM2๋ก ์ด์์ ธ์ p53 ์กฐ์ P53-MDM2 feedback loop?Sequestering mdm2 in nucleolusArf stabilizes p53 by ...P53-p21-RbP53์ pathway ์ค cell cycle arrest์ ๊ด์ฌํ๋ pathwayHypophosphorylationP21์ pRB๋ฅผ (hypophosphorylation/hyperphosphorylation) ์ํจ๋ค.Transcription activating of pro-apoptotic gene, binding to bcl-2 and bcl-xP53 induces apoptosis by ...Bax, Bcl-x... is released by p53 from ... and forms oligomers, leading to apoptosisAntioxidant, prooxidantP53์ normal cell์์์ target gene์ (pro-oxidant/antioxidant) gene์ด๊ณ , extended stress ์ํฉ์์์ target gene์ (pro-oxidant/antioxidant) genePdk, akt, cell survival proliferationPIP3์ด ์๊ธฐ๋ฉด ...๋ฅผ ๊ฑฐ์ณ ...๊ฐ activation๋์ด ...๋ฅผ ์ด์งํ๋ค.Glioblastoma, endometrial cancer, prostate cancer, melanomaSomatic mutation of PTEN์ ์ํด ๋ํ๋๋ disease?Germline, familial adenomatous polyposis(Germline/Somatic) mutation in APC gene result in ...Fap, AD๋ณ๋ช
๊ณผ ์ ์ ์์C terminally truncated APCMutant form of APC?Inflammatory mediator, cox2, RONS, inflammatory cytokineChronic inflammation alters the cellular level of ... including ..., ..., ...DNA structure, stabilityConventional chemotherapy๋ ... ๋ ...์ ์ํฅ์ ์ค๋ค.Surgical treatment, radiotherapy, chemotherapy, targeted therapy, checkpoint inhibitorHistory of cancer therapy ์์๋๋ก
Checkpoint inhibitor, chemotherapy, radiotherapy, surgical treatment, targeted therapyCytostatic, prevent proliferation, cytotoxic, kill cellsPrinciple of conventional cancer therapies
- ... effect : to ...
- ... effect : to ...Minimum effective dose, maximum tolerated doseTherapeutic index is a value of difference between ... and ...Broad, mtdConventional cancer therapies are (narrow/broad) acting drugs administered at (MED/MTD)Alopecia, ulcer, anemiaSide effects of chemotherapyAlkylating agentChemical carcinogen์ด์ง๋ง ๊ฒฐ๊ตญ์ apoptosis ์์ผ์ cytotoxic drug๋ก์ anti cancer drug์ ์ฐ์ด๋ ๊ฑด?Folate antagonist, pyrimidine antagonist, purine antagonistCytotoxic drug ์ค antimetabolites๋ฅ๊ฐ ์๋ค. ์ด๋ฅผ ์ธ๊ฐ์ง๋ก ํฌ๊ฒ ๋๋๋ฉด?MicrotubuleCytotoxic drug ์ค์ vinca alkaloid, taxanes, estramustine ๋ฑ์ ... damaging agent๋ค์ด๋ค.ToposiomeraseCytotoxic drug ์ค DNA replication ๋ ... inhibitor๋ก ์์ฉํ๋ ๊ฒ๋ ์๋ค.Safety, efficacy, efficacy often tested against conventional treatmentsPurpose of clinical trials of phase 1, 2, 3Kinase/phosphatase, ras family, p53, rbMolecule of Fame in cancer therapySingle nucleotide polymorphism, small interfering RNACancer genomics
... : to identify mutation within the genome that may be linked with cancer
... : interfere with the expression of specific genesmRNA cleavage, fully, translational inhibition, partiallySiRNA์ ์ญํ : ... - (... complementary)
MiRNA์ ์ญํ : ... - (... complementary)Efflux, mdr, influx, metabolism, compartmentalization, mutation, altered, dna repair, apoptoticAnticancer drug resistance
1. Increasing .. of drug : ... gene
2. Decreasing ... of drug
3. increased drug inactivation by ...
4. Drug ...
5. ... of cellular target
6. ... drug targets
7. Enhanced ...
8. Inactivation of ... pathwaymultiple initial cloneMajor impediment in treatment of treatment of cancer : presence of ...Apoptosis, dna synthesisTherapeutic strategy (DNA structure & stability) in conventional therapy
1. Induction of extensive DNA damage -> trigger ...
2. Inhibition of DNA metabolism -> block ...Thymidylate, folateChemotherapeutic agent (antimetabolite) ... synthesis and ... metaboism as target for chemotherapyMethotrexate, 5-florouracilDihydrofolate reductase๋ฅผ ๋ง๋ chemotherapeutic agent : ...
thymidylate synthase๋ฅผ ๋ง๋ chemotherapeutic agent : ...Epigenomic, DNMT, HDAC, telomeraseํ์ ํญ์์ ์์ ... drug์ ์ฌ์ฉํ๋ค. Inhibitor of ... for tumor suppressor gene, inhibitor of ... for tumor suppressor gene, ... inhibitor๊ฐ ์ฌ์ฉ๋๋ค.Monoclonal antibody, herception, iressa, gleevec, farnesyltransferase inhibitor, caax, antisenseTherapeutic strategies - oncogene activators
- EGF receptor : ... (ex. ...)๋ฅผ ๋ถ์ด๋ฉด Her2/neu receptor๊ฐ ๋ฐฉํด
- ... : kinase inhibitor against EGF-R family
- ... : abl kinase ๋๋ c-kit kinase๋ฅผ inhibit
- ... : compete with ... motif of Ras
- ... oligonucleotides to raf RNACaspase, smac, bcl-2, antimycin A, saha induced Bid cleavagetherapeutic strategy - apoptotic drug
1. Activation of ...
(XIAP inhibitor : ... peptide)
2. Regulation of ... family (...๊ฐ ์ด ์ญํ ์ ํ๋ค. ๋๋ ...)Fas ligand, TNF related apoptosis inducing ligandApoptosis pathway๊ฐ ์ ๋์๊ฐ ์ค ์์๋๋ฐ liver toxicity๊ฐ ๋๋ฌด ์ฌํ ๋ฐฉ๋ฒ? ๊ทธ๋ผ ๊ทธ๊ฑฐ๋ ๊ฐ์ ๊ธฐ์ ์ผ๋ก ์ฐ๋ ๋ค๋ฅธ ๋ฐฉ๋ฒ?Mutation compensation, molecular chemotherapy, genetic immunotherapy and tumor vaccinationGenetherapy์ ์ธ๊ฐ์ง ๊ธฐ์ ?ablation, replacement, interferenceMutation compensation
1. ... of oncogene product
2. ... of tumor suppressor gene
3. ... with dysregulated signal transduction pathwayChemosensitization, herpes simple virus-thymidine kinase, gencyclovir, chemoprotection, mdr-1, bone marrow cellMolecular chemotherapy
1. ... : suicide gene therapy (ex. ... gene & ...)
2. ... : introduction of ... gene into ...Dendritic cell vaccineGenetic immunotherapy/tumor vaccination์ ํ์ฉ๋๋๊ฑฐ?Monocyte, cd34, natural dc, immature dc, maturation factor, tumor antigen, mature DC, apoptosis<tumor vaccination>
1. Apheresis๋ฅผ ํตํด ..., ..., ... ๋ฑ์ ์ฑ์ทจํ๋ค
2. 1์์ ์ฑ์ทจํ ๊ฒ๋ค์ growth factor๋ฅผ ์ค์ ...๋ฅผ ๋ง๋ค์ด๋ธ๋ค.
3. 2์ ๊ฒฐ๊ณผ๋ฌผ์ ...๋ฅผ ๋ฃ๊ณ ...๋ฅผ expose์ํค๋ฉด ... ๋ฅผ ๋ง๋ค์ด๋ผ ์ ์๋ค.
4. ์ด๊ฑธ ๋ค์ ๋ชธ ์์ ๋ฃ์ผ๋ฉด cytotoxic T cell์ด ๋ง๋ค์ด์ ธ์ tumor cell์ ...๋ฅผ ์ด๋ํ ์ ์๋ค.
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