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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 : ... 넘기 전Escape 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 cell에서 leukemia가 발생하는 순서는? 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 gene은 어떤 repair process에 의해 고쳐지는지?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 중 increased proliferation에 관여하는 거?Unlimited replicative potentialHallmark of cancer 중 increased self renewal에 관여하는 거?Loss of DNA repair systemHallmark of cacner 중 Genomic instability에 관여하는 거?Evasion of apoptosisHallmark of cancer 중 increased cell survival에 관여하는 거?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 development를 증명하기 위한 실험에서 사용한 두 가지의 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. 이름 2. 화살표 친 부분은 뭐랑 반응? 3. 4개의 ring은 어디에 위치?Aromatic aminesAminobiphenyl은 무엇의 예시?N(7)-MeG, O(6)-MeGNitrosamine에서 ultimate carcinogen이 만들어지면?Pseudo watson-crick pair, wobble pair, pO(6)-MeG에 의해 만들어질 수 있는 pair? 둘 중 문제 있는 것의 첫 글자?Intrastrand linking, cross linkngAs genotoxic chemical carcinogen, bifunctional alkylating agent can cause ... and ...IonizingX-rays, γ 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 break는 ionizing radiation vs non ionizing radiation 중 뭐에 의한 것?Non ionizing radiationKink by thymine dimer는 ionizing radiation vs non ionizing radiation 중 뭐에 의한 거?UVBMost effective carcinogenAging of skin, pigmentation, sunburn, skin cancer, absorbed in ozone layerUVA -> ..., ... UVB -> ..., ... UVC -> ...UVB, CPD, 6-4 ppsAdjacent T bases는 ...에 의해 ...와 ...로 나뉜다.Inhibition of tumor suppression, viral oncogenes and insertional activationDNA tumor virus의 역할 : RNA tumor virus의 역할 :Hepatic cancer, cervical cancer, burkitt's lymphoma and hodgkin's lymphomaDNA virus와 관련된 tumor HBV -> HPV -> EBV ->Rb, p53Viral protein이 결합하는 tumor suppressor gene?pRB, E2F, pRB, p53(A) ...는 ...이 cell cycle을 진행시키지 못하도록 한다 (B) DNA tumor virus는 ...와 결합하여 원래 작용을 하지 못하게 되어 cell cycle progression 시킨다 (C) DNA tumor virus가 ...에 붙으면 cell cycle arrest 시킨다Carry oncogene, alter transcriptional regulationAcute transforming retrovirus는 ... , slow transforming retrovirus는 ... .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-oxoguanine이 생기는 기전 두가지?Deamination, hydrolysis, glycosidic bond, abasic siteSpontaneous chemical reaction - ... of cytosine to form uracil - ... of ... between base and deoxyribose -> producing ...Translesion synthesis, low fidelity polymerasesAP site가 tolerance 생기면 -> ... -> 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, acetylationHistone의 ... 는 condense form을, ...는 relaxed form을 유도한다histone 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 inhibition에만 관여하는 음식?Cashew nuts, grapes, garlicHistone modification에만 관여하는 음식?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 genome에는 gag, pol, env가 있다. 각각 어떤 protein을 encoding할까?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 gene이 관여하는 것은?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 negative하게 유전되는 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, MycmitogensTgfβ, 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 phase에 만들어지는 D-CDK4/6 complex의 inhibitor?p21, p27, p57ECDK2, ACDK2, ACDC2, BCDC2 inhibitorCyclin D1, p16, Rb, TGFβ, TGFβ, 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 (..., ...) (I— 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-8는 inactive한 ...를 거쳐 active한 ...를 통해 작용한다.Bcl-x, apoptosis, survival, AktBad는 ...의 작용을 받으면 pro-apoptotic한 상태를 유지한다. 작용이 사라지면 ...를 이끌 수 있고, 14-3-3 phosphorylation되면 ...를 이끈다. 이를 조절하는 건 ... 이다.PI3 kinasePIP2 -> PIP3phosphatase and tensin homologPIP3 -> PIP2AktSurvival factorPTENDeletion of (PI3 kinase/PTEN) is frequent occurence in human tumorPIP3, PTEN, PIP3PIP3 vs PIP2 중 cell progression을 일으키는 건 ... 따라서 tumor suppressor gene 역할을 하는 ...가 depletion 되어 ...가 쌓이는 것이 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, phosphotyrosineSrc에서 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 : 527번째 아미노산인 ...가 ... domain과 붙어 있다. - partially active : PDGF-R 등 Src activator가 오면 pdgf receptor의 ... domain에 phosphotyrosine이 붙어서 ... - fully active : ... inactive 상태에서는 ...가 중요한 역할을 하는데, v-src에는 이게 없어서 계속 ...Mutant form of receptor tyrosine kinaseProto oncogene이었던 growth factor receptor와 달리 oncogene이 되면 ...Tyrosine kinase activitymajority of oncogene derived from growth factor receptor : ...Dimer, ligand, ligand independent firingGFR는 ...를 형성해서 ... dependent firing을 되는데, mutation이 생기면 ...Point mutation, neu, deletion, ErbB1, translocation, with ETV6HER2 -(...)-> ... EGF-R1 -(...)-> ... PDGF receptor -(...)->Epo, erythropoietin proliferation, gp55, firing, erythroleukemia...라고 하는 erythropoietin은 growth factor receptor에 붙어서 ...에 필요한데, viral oncoprotein 중에 ...가 구조가 유사하여 receptor가 계속 ... 한다. 그 결과 ...가 초래된다.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...는 E6 & E7 protein을 release한다. E6 protein은 ...에 붙어 ...로 작용하고, E7 protein은 ...에 붙어 그 역할을 방해해서 ...의 결과로 작용한다.RasMutations in ... gene are found in about 30% of human cancersguanine nucleotide exchange factor, gdp-GTP exchange, GTPase activating protein, dephosphorylationras proto-oncogene은 ...에 의해 ...되며 activation 되고, ...에 의해 ...되며 inactivation 된다.Translocation of cytosolic Ras protein to cell membraneProcess essential to RAS activationGTPaseRas protooncogene과는 다르게 ras oncogene은 ... enzyme의 작용이 잘 일어나지 않아서 cancer를 유발한다Point mutationRas protooncogene에 어떤 mutation이 일어나야 oncogene이 될까?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 cancerI는 모든 cell들에 germline mutation에 의한 first hit을 기본적으로 가지고 있기 때문에, 어떤 cell이든 rb gene에 coding sequence의 문제이건 epimutation의 문제이건 loss of function을 일으키는 mutation이 일어나면 retinoblastoma가 생긴다. S는 같은 tissue의 같은 cell에 loss of function을 일으키는 mutation이 두 번이나 일어나야 retinoblastoma로 develop하기 때문에 그 chance가 줄어든다.Two hit hypothesis inherited retinoblastoma : ... sporadic retinoblastoma : ...Loss of heterozygosityMutant heterozygote는 mutant homozygote가 되기 유독 쉽다. 이유는?Non disjunction, mitotic recombinationLoss of heterozygosity의 대표적인 두 가지 기전?Chromosome loss, deletion, unbalanced translocation, point mutationNondisjunction과 mitotic recombination을 제외한 loss of heterozygosity의 기전 4가지?Regulate level of β catenin proteinAPC의 원래 역할 : ... in cytosolMDM-2 protein stability, p53 stabilityP14art : regulate ... and hence ...Nf-1Ras-GTPase의 gene?Transcriptional factor of TGF-βSmad4?TSE-cad는 oncogene or tumor suppressor?Dna mismatch repairMSH2, MLH1, PMS1, PMS2, MSH6의 역할?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 일한결과?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, lowMDM2가 와서 붙으면 p53은 (phosphorylation/ubiquitination) reaction이 일어나 p53 (high/low)상태가 된다.Mdm2는 p53의 target gene이여서 p53이 stabilized되면 high level of MDM2로 이엉져서 p53 조절P53-MDM2 feedback loop?Sequestering mdm2 in nucleolusArf stabilizes p53 by ...P53-p21-RbP53의 pathway 중 cell cycle arrest에 관여하는 pathwayHypophosphorylationP21은 pRB를 (hypophosphorylation/hyperphosphorylation) 시킨다.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, prooxidantP53의 normal cell에서의 target gene은 (pro-oxidant/antioxidant) gene이고, extended stress 상황에서의 target gene은 (pro-oxidant/antioxidant) genePdk, akt, cell survival proliferationPIP3이 생기면 ...를 거쳐 ...가 activation되어 ...를 촉진한다.Glioblastoma, endometrial cancer, prostate cancer, melanomaSomatic mutation of PTEN에 의해 나타나는 disease?Germline, familial adenomatous polyposis(Germline/Somatic) mutation in APC gene result in ...Fap, AD병명과 유전양상C terminally truncated APCMutant form of APC?Inflammatory mediator, cox2, RONS, inflammatory cytokineChronic inflammation alters the cellular level of ... including ..., ..., ...DNA structure, stabilityConventional chemotherapy는 ... 나 ...에 영향을 준다.Surgical treatment, radiotherapy, chemotherapy, targeted therapy, checkpoint inhibitorHistory of cancer therapy 순서대로 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 carcinogen이지만 결국은 apoptosis 시켜서 cytotoxic drug로서 anti cancer drug에 쓰이는 건?Folate antagonist, pyrimidine antagonist, purine antagonistCytotoxic drug 중 antimetabolites류가 있다. 이를 세가지로 크게 나누면?MicrotubuleCytotoxic drug 중에 vinca alkaloid, taxanes, estramustine 등은 ... damaging agent들이다.ToposiomeraseCytotoxic drug 중 DNA replication 때 ... inhibitor로 작용하는 것도 있다.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, partiallySiRNA의 역할 : ... - (... complementary) MiRNA의 역할 : ... - (... 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 reductase를 막는 chemotherapeutic agent : ... thymidylate synthase를 막는 chemotherapeutic agent : ...Epigenomic, DNMT, HDAC, telomerase표적항암제에서 ... drug을 사용한다. Inhibitor of ... for tumor suppressor gene, inhibitor of ... for tumor suppressor gene, ... inhibitor가 사용된다.Monoclonal antibody, herception, iressa, gleevec, farnesyltransferase inhibitor, caax, antisenseTherapeutic strategies - oncogene activators - EGF receptor : ... (ex. ...)를 붙이면 Her2/neu receptor가 방해 - ... : kinase inhibitor against EGF-R family - ... : abl kinase 또는 c-kit kinase를 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 (...가 이 역할을 한다. 또는 ...)Fas ligand, TNF related apoptosis inducing ligandApoptosis pathway가 잘 돌아갈 줄 알았는데 liver toxicity가 너무 심한 방법? 그럼 그거랑 같은 기전으로 쓰는 다른 방법?Mutation compensation, molecular chemotherapy, genetic immunotherapy and tumor vaccinationGenetherapy의 세가지 기전?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 vaccination에 활용되는거?Monocyte, cd34, natural dc, immature dc, maturation factor, tumor antigen, mature DC, apoptosis<tumor vaccination> 1. Apheresis를 통해 ..., ..., ... 등을 채취한다 2. 1에서 채취한 것들에 growth factor를 줘서 ...를 만들어낸다. 3. 2의 결과물에 ...를 넣고 ...를 expose시키면 ... 를 만들어낼 수 있다. 4. 이걸 다시 몸 안에 넣으면 cytotoxic T cell이 만들어져서 tumor cell의 ...를 초래할 수 있다.