王照元 高雄醫學大學附設醫院 外科¤§腸癌症之...Jaw-Yuan Wang...
Transcript of 王照元 高雄醫學大學附設醫院 外科¤§腸癌症之...Jaw-Yuan Wang...
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JawJaw--Yuan WangYuan Wang
大腸直腸癌分子致病機轉大腸直腸癌分子致病機轉
王照元高雄醫學大學附設醫院
外科
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CancerCancer
A genetic disease, but in most cases, it is A genetic disease, but in most cases, it is not an inherited diseasenot an inherited disease
The genetic alterations that lead to most The genetic alterations that lead to most cancers arise in the DNA of a somatic cellcancers arise in the DNA of a somatic cell
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Incidence and mortality of colorectal Incidence and mortality of colorectal carcinoma in the USA over the past 6carcinoma in the USA over the past 6 years years
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Taiwan (2000): Male: 37.29; Female: 28.81
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Gene Environment
GatekeeperGene
CaretakerGene
ExogenousAgents
EndogenousAgents and Mechanism
Causes of Genetic diseaseCauses of Genetic disease
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大腸直腸癌腫瘤形成的模式,從正常黏膜經腺瘤階段 進行至癌症,是由一連串基因的改變,積聚而成。研 究顯示從正常大腸直腸黏膜變成大腸直腸腺性瘜肉平 均所需時間約為十年,從腺性瘜肉成為大腸直腸癌則 約需五年時間
大腸直腸癌的形成
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Colorectal carcinoma develops along a ‘classical’ pathway outlined by Fearon and Vogelstein (1990)
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Somatic mutations that cause Somatic mutations that cause sporadic colorectal sporadic colorectal neoplasianeoplasia
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The 2 main types of genes The 2 main types of genes are playing a role in cancer are playing a role in cancer are are oncogenesoncogenes and and tumor tumor
suppressor genessuppressor genes
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Functional Properties of Functional Properties of OncogenesOncogenes
Transformation events in cancer have Transformation events in cancer have been defined as initiation events or been defined as initiation events or progression eventsprogression events
OncogenesOncogenes encode proteins that control encode proteins that control cell proliferation, apoptosis, or bothcell proliferation, apoptosis, or both
Activated by structural alterations resulting Activated by structural alterations resulting from mutation or gene fusion or from mutation or gene fusion or amplification amplification
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Products of Products of OncogenesOncogenes
Chromatin remodelersChromatin remodelers
Growth factorsGrowth factors
Growth factor receptorsGrowth factor receptors
Signal transducersSignal transducers
Transcription factorsTranscription factors
Apoptosis regulators Apoptosis regulators
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OncogeneOncogene ActivationActivation
Chromosomal rearrangementsChromosomal rearrangements
chromosome inversions and translocations chromosome inversions and translocations
MutationsMutations
RASRAS oncogenesoncogenes ((KRAS, HRAS,KRAS, HRAS, and and NRASNRAS), ), which encode proteins with which encode proteins with guanosineguanosine-- nucleotidenucleotide––binding activity and intrinsic binding activity and intrinsic guanosineguanosine triphosphatasetriphosphatase activityactivity
Gene amplificationGene amplification
usually occurs during tumor progression usually occurs during tumor progression
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Single nucleotide polymorphismsSingle nucleotide polymorphisms
55’’..........C C A T T G A CC C A T T G A C..........33’’55’’..........G G T A A C T GG G T A A C T G..........33’’
55’’..........C C G T T G A CC C G T T G A C..........33’’55’’..........G G C A A C T GG G C A A C T G..........33’’
Transition: Transition: pyridiminepyridimine pyridiminepyridimine (C,T)(C,T)purinepurine purinepurine (A, G)(A, G)
TransversionTransversion: : pyridiminepyridimine purinepurineTransition > Transition > transversiontransversion
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FrequencyFrequency RareRare Common(>1% of a population)Common(>1% of a population)
Distribution in genomeDistribution in genome Primarily in genesPrimarily in genes Majority in interMajority in inter--genicgenic regionsregions
Density Density ~1,200 in OMIM*~1,200 in OMIM* ~15 million in genome(>5 million with ~15 million in genome(>5 million with frequency>10%)frequency>10%)
PenetrancePenetrance HighHigh Low (minority)Low (minority)
No effect (majority)No effect (majority)
Clinical utilityClinical utility Molecular Molecular diagnosisdiagnosis
Confers risk (still investigational)Confers risk (still investigational)
*Reported in On-line Mendelian Inheritance of Man(OMIM)data-base(http://www.ncbi.nlm.nib.gob/OMIM)
Critical Differences Between SNPs and Mutations
SNPMutation
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EnvironmentEnvironment--Susceptibility Susceptibility InteractionInteraction
Carcinogens: chemicals or physicalCarcinogens: chemicals or physical
InitiationInitiation
Bind to DNA adduct, DNA changeBind to DNA adduct, DNA change
PromotionPromotion
Altered signal transduction, cell abnormal Altered signal transduction, cell abnormal proliferationproliferation
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致癌物代謝酵素的致癌物代謝酵素的genetic genetic polymorphismpolymorphism
致癌物的代謝酵素致癌物的代謝酵素
PhasePhase--I enzyme: I enzyme: 將致癌化合物代謝成親電將致癌化合物代謝成親電 子的代謝物子的代謝物, , 因而能活躍地與因而能活躍地與genomegenome的的 DNADNA
結合成結合成adduct, adduct, 以致造成基因的改變以致造成基因的改變, e.g. , e.g. cytochromecytochrome pp--450450--dependent dependent monooxygenasemonooxygenase: CYP1A1: CYP1A1
PhasePhase--II enzyme:II enzyme:將致癌化合物轉變成親水將致癌化合物轉變成親水 性的代謝物性的代謝物, e.g. Glutathione, e.g. Glutathione--SS--transferasetransferase
能將能將polycyclic aromatic polycyclic aromatic hydrogenasehydrogenase解毒解毒
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致癌物代謝酵素的致癌物代謝酵素的genetic genetic polymorphismpolymorphism
只有暴露於低劑量致癌物的情況下只有暴露於低劑量致癌物的情況下,,基因多型性基因多型性 與致癌關係才會明顯有意義與致癌關係才會明顯有意義
調控致癌物代謝之某種特殊基因型態調控致癌物代謝之某種特殊基因型態,,由於表現由於表現 率相當低率相當低,,因此病例數要相當大才能看出關聯性因此病例數要相當大才能看出關聯性
致癌物與致癌物代謝酵素常是多種混在一起相致癌物與致癌物代謝酵素常是多種混在一起相 互作用互作用
致癌物的解毒與活化在不同個體間的差異並不致癌物的解毒與活化在不同個體間的差異並不 是完全由基因所決定的是完全由基因所決定的
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Genetic Polymorphism and Genetic Polymorphism and Colorectal CancersColorectal Cancers
活躍的活躍的CYP1A1CYP1A1酵素的基因型確實與大腸直腸癌的致癌酵素的基因型確實與大腸直腸癌的致癌 過程有關過程有關
具快速具快速NN--acetyltransferaseacetyltransferase (NAT) (NAT) 酵素的基因型會更有酵素的基因型會更有 效地將肉類的效地將肉類的heterocyclic aromatic aminesheterocyclic aromatic amines活化活化,,這些人這些人 較易得到大腸直腸癌較易得到大腸直腸癌
十字花科蔬菜之所以能預防大腸直腸癌乃是透過十字花科蔬菜之所以能預防大腸直腸癌乃是透過 GlutathioneGlutathione--SS--transferasetransferase (GST)(GST)活性增加所致活性增加所致
MethylenetetrahydrofolateMethylenetetrahydrofolate reductasereductase (NTHFR) (NTHFR) 的遺傳的遺傳 多型性與大腸直腸癌有相關多型性與大腸直腸癌有相關: variant homozygous (TT): : variant homozygous (TT):
發生率最低發生率最低, variant heterozygous (CT), wild type , variant heterozygous (CT), wild type homozygous (CC)homozygous (CC)
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飲食因素(高脂肪, 低纖維; 抽煙)
a) 食物纖維: 第一個主要理論 快速通過時間會降低致癌物質與大腸黏膜接觸的時間
b) 食物脂肪: 第二個主要理論 但大腸癌與fat-protein consumption無法平行
c) 食物糖分 d) 腸道菌叢的改變(Alternation in bowel microflora)
e) DeVita 認為目前低脂高纖的飲食是明智的f)卡路里或酒精攝取過量; 肥胖g)膽酸分泌
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Bile acids and colon cancer (Reddy et al.,1977; Kulkarni et al.,1982; Ksndell et al.,1991; Carol et al.,1999;Glinghammar et al., 2002; Lechner et al., 2002; Wachs et al., 2005):
Oxidative stress
DNA damage
Mitochondrial membrane instabilityBile acid possibly play an important intermediate role in the cell proliferation, but the mechanism is not well understood (European Journal of Cancer, 1956).
Synthesis0.4-1.2 mmol/Day
Small Bowel
Colon
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肥胖、體能活動、以及能量攝取肥胖、體能活動、以及能量攝取
肥胖對大腸直腸癌的影響在男性比女性明肥胖對大腸直腸癌的影響在男性比女性明 顯顯
體能活動較旺盛者罹患大腸直腸癌的機會體能活動較旺盛者罹患大腸直腸癌的機會 較低:大腸直腸黏膜的較低:大腸直腸黏膜的PGE2 PGE2 濃度較低濃度較低
個人的總能量攝取與大腸直腸癌有正相關個人的總能量攝取與大腸直腸癌有正相關
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Gene name APC K-ras p53Adenomatous polyposis coliDiscovery
20-30% humancancers
50% human Solid tumors
Gatekeeper gene, tumor suppressor gene
Proto- Oncogene, GTP binding protein
Tumor suppressor gene, transcription factor
Function
Mutational
Hot spots
Codons 1286~1513
Codons 12,13& 61
Exons 5 ~ 8
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APC K-ras p53MutationsIncidence
52 /118 (44.1%) 54 /118 (45.8%) 43 /118 (36.4%)
MutationsType
29/118 missense10/118 frameshift6/118 nonsense 6/118 silent 1/118 deletion
44/118 missense3/118 frameshift3/118 silent 2/118 nonsense
30/118 missense6/118 frameshift6/118 silent 3/118 nonsense
Hot spots(cases)
1259 (3), 1263 (2), 1285 (2), 1288 (2), 1296 (2), 1326 (2),1331 (2), 1404 (2), 1560 (2), 1565 (2), 1581 (2), 1582 (2), 1605 (2)
12 (14), 13 (10), 15 (8), 18 (3), 20 (3), 21 (2), 27 (2), 30 (2)
175 (3), 194 (2), 207 (2), 209 (5), 245 (2), 248 (2), 267 (2), 273 (2), 282 (2)
New Finding
1259,1263,1285, 1560,1565,1581, 1582,1605並不在
mutation cluster region
突變熱點中30% (14/47)是在codon 15,另外codons 18,
20,21,27,30是未曾 在CRC報告過
codons 194,207, 267,282是文獻未曾在
大腸直腸癌上發現的
Results of KMUH
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12.2%
17.1%
9.8%26.8%
17.1%
12.2% 4.9%APC
K-ras
p53
APC + K-ras
APC + p53
K-ras + p53 APC + K-ras + p53
Mutation Frequency of APC, K-ras, p53 in Taiwanese CRC
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Our data Smith et al.APC 44.1% 60%K-ras 45.8% 30%P53
Only one gene mutation
36.4%
41.3%
61.3%
38.7%
Three gene mutations 5% 6%≧1 gene mutations 77.1% 88.7%
本研究 Smith et al.APC missense 突變 nonsense 突變、frameshift
K-ras
Combine
codon 15
most APC+K-ras
codon 12、codon 13
most APC+p53
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0
10
20
30
40
50
60
A B C D
Dukes' stage
Tum
ors
anal
yze
d (
%)
APC
K-ras
p53
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Microarray Ratio Northern blotting ratio GenBank Identity/Symbol CRC-related GenBank
(carcinoma/adenoma/normal) (carcinoma/adenoma/normal) Accession number
(41.35/26.12/1) (43.86/21.12/1) Capping protein (actin filament) muscle Z-line, alpha 1/(-) NM_006135 CAPZ1
(18.26/4.87/1) (24.65/4.02/1) Ecotropic viral integration site 2B/EVI2B Unknown NM_006495(16.88/4.78/1) (11.24/3.27/1) ATPase, Ca++ transporting, cardiac muscle, (-) NM_001681
slow twitch 2/ATP2A2(11.29/4.95/1) (13.76/4.36/1) KIAA0176 protein/ KIAA0176 (-) D79998(10.35/6.05/1) (10.97/4.80/1) S100 calcium binding protein, beta (neural)/S100B (-) NM_006272(7.58/3.73/1) (8.88/3.38/1) Kallikrein 7 (chymotryptic, stratum corneum)/KLK7 (-) NM_005046(6.54/4.05/1) (7.25/3.71/1) Decay accelerating factor for complement (+) NM_000574
(CD55, Cromer blood group system)/DAF(5.75/3.90/1) (6.08/3.26/1) Guanine nucleotide binding protein (G protein), (+) NM_006098
beta polypeptide 2-like 1/G protein(5.36/2.54/1) (20.75/3.75/1) ELAV (embryonic lethal, abnormal vision, Drosophila)-(-) NM_021952
like 4 (Hu antigen D)/EVLAVL4 (5.09/2.48/1) (32.67/4.33/1) Transmembrane 4 superfamily member 3/TM4SF3 (+) NM_004616 (4.85/3.01/1) (5.98/3.23/1) Kallikrein 1, renal/pancreas/salivary/KLK1 (+) NM_002257 (4.23/2.05/1) (8.08/2.56/1) Keratin 4/KRT4 (-) NM_002272 (3.96/3.03/1) (19.46/2.75/1) Formin binding protein 3/FNBP3 (-) BC027178 (3.59/2.12/1) (3.29/2.05/1) Haptoglobin/HP (+) NM_005143(3.56/2.28/1) (6.81/3.04/1) Homo sapiens chromosome 21q22.1 anonymous Unknown AF003738
mRNA sequence/chromosome 21q22.1(3.48/3.01/1) (5.51/3.20/1) Solute carrier family 25 (mitochondrial carrier; (-) NM_001151
adenine nucleotide translocator), member 4/SLC25A4(3.44/2.43/1) (20.67/4.59/1) Peptidylprolyl isomerase B (cyclophilin B)/PPIB (-) NM_000942(3.39/2.17/1) (4.34/2.32/1) H2A histone family, member Y/H2AFY (-) NM_004893(3.28/2.29/1) (3.06/2.13/1) Homo sapiens DMR protein mRNA/DMR Unknown AF327354(3.18/2.10/1) (4.21/2.29/1) Nerve growth factor receptor (-) NM_00250
(TNFR superfamily, member 16)/NGFR(3.17/2.31/1) (3.28/2.45/1) Laminin receptor 1 (67kD, ribosomal protein SA) (+) NM_002295
/LAMR1(3.09/2.52/1) (3.17/2.30/1) Small inducible cytokine subfamily A (Cys-Cys), (-) NM_004591
member 20/SCYB11(3.02/2.18/1) (3.82/2.38/1) Eukaryotic translation elongation factor 1 alpha 1 (+) NM_001402
/EEF1A1
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Gene OntologyGene Ontology
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Possible invasion and metastasis-associated genes
Possible invasion and Possible invasion and metastasismetastasis--associated genesassociated genes
Capping protein muscle ZCapping protein muscle Z--line, alpha 1line, alpha 1 is involved in cell is involved in cell motilitymotility
ATPaseATPase, Ca, Ca++++ transporting, slow twitch 2 transporting, slow twitch 2 andand lamininlaminin receptor 1 are involved cell adhesionreceptor 1 are involved cell adhesion
ChemokineChemokine ligandligand 2020 is involved in is involved in chemokinechemokine activityactivity
Guanine nucleotide binding protein Guanine nucleotide binding protein ββ--subunitsubunit and and nerve nerve growth factor receptorgrowth factor receptor are involved in signal transductionare involved in signal transduction
Keratin 4Keratin 4 is involved in cytoskeleton organization is involved in cytoskeleton organization
KallikreinKallikrein 11, , kallikreinkallikrein 77, , haptoglobinhaptoglobin and and H2A H2A histonehistone family, member Yfamily, member Y are involved in proteolysis are involved in proteolysis
S100 calcium binding protein, betaS100 calcium binding protein, beta is involved in cell is involved in cell proliferationsproliferations
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Genes are demonstrated to be considerably correlated to tumor
invasion and metastasis
Genes are demonstrated to be Genes are demonstrated to be considerably correlated to tumor considerably correlated to tumor
invasion and metastasis invasion and metastasis
Laminin receptor 1 that is overexpressed on the tumor cell surface in a variety of cancers plays a major role in tumor aggressiveness and metastasis
Kallikrein 7 may play an important role in invasion and metastasis of ovarian and cervical cancers
A haptoglobin-related glycoprotein is implicated in tumor progression and metastasis of colorectal cancers
S100 calcium binding protein, beta appears to be the most appropriate tumor marker for newly occurred melanoma metastases
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Functional categories of upFunctional categories of up--regulated or downregulated or down-- regulated genes in Colorectal Cancerregulated genes in Colorectal Cancer
15 14
62
2 3
107
4 4
29
1 1
74
transcription transcription,DNA-dependent
metabolism nucleosome myosin receptor bindingactivity
cytokine activity
Functional (Term)
Gen
e Ex
pres
sed
(N)
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down-regulated up-regulated
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Gene Expression
Pathwayanalysis
Gene Ontology(GO)
MAPPFinder/GoMiner
Spotfire &&GenMAPPand DAVID
大腸直腸癌癌化之分子
模式假說
代謝途徑的分析
脂肪酸代謝 膽酸代謝 醣類水解 缺氧機轉
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Gene Description Function
EHHADH enoyl-Coenzyme A, hydratase/3- hydroxyacyl Coenzyme A dehydrogenase
catalyzing the second and third step of peroxisomal fatty acid beta-oxidation of very long chain fatty acids, but not bile intermediates
ECHS1 enoyl Coenzyme A hydratase, short chain, 1, mitochondrial
The second step in mitochondrial fatty acid beta- oxidation
GCDH glutaryl-Coenzyme A dehydrogenase glutaryl-CoA dehydrogenase, flavoprotein dependent, lysine oxidation
COX2 acyl-Coenzyme A oxidase 2, branched chain
peroxisomal branched chain trihydroxypristanoyl-CoA oxidase
ACADS acyl-Coenzyme A dehydrogenase, C-2 to C-3 short chain precursor
catalyzing the initial step of the mitochondrial fatty acid beta-oxidation pathway
CPT1B carnitine palmitoyltransferase 1B trans-esterification of medium and long chain fatty acyl,chains converting palmitoyl carnitine into palmitoyl-CoA (palmitoyl-CoA shuttle)
ACSL5 acyl-CoA synthetase long-chain family member 5
converting free long-chain fatty acids into fatty acyl CoA esters
CYP4A11 cytochrome P450, family 4, subfamily A, polypeptide 11
hydroxylation of medium chain fatty acid such as laurate and myristate
Normal subjectNormal subject CColon cancer patientolon cancer patient
EHHADH ECHS1 GCDH
COX2 ACADS CPT1B
ACSL5 CYP4A11 β-actin
EHHADH ECHS1 GCDH
COX2 ACADS CPT1B
ACSL5 CYP4A11 β-actin
Fatty acid metabolism relevant gene
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Linoleic acid (n-6 PUFAs)
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α-D-Glucose
β-D-Glucose
GLAM
HK1, GCK
HK1, GCKβ-D-Glucose-6P
α-D-Glucose-6P(aerobic decarboxylation)
β-D-Glucose-6PGPI
GPIGPI
β-D-Fructose-1,6P2
PFKLPFKMPFKP
FBP1FBP2
Glyceraldehyde-3P
Glycerate-1,3P2
Glycerate-3P
Glycerate-2P
Phosphoenol-Pyruvate
Pyruvate
α-D-Glucose-1P
ALDOA, ALDOB ,ALDOC
GAPD
ACYP1ACYP2
PGK1PGK2
Glycerate-2,3P2
PGM1, PGM3
PGAM1, PGAM2, BPGM
ENO1, ENO2, ENO3
PKLR, PKM2
L-LactateLDHA, LDHB, LDHC
G6PC
TPI1Glycerone-P
PGAM1, PGAM2, BPGM
PGAM1, PGAM2, BPGM
Glucose
GLUT1GLUT3
Cell Membrane
1. HK 1: Hexokinase2. GPI: Phosphoglucose isomerase3. PFKL: Phosphofructokinase4. ALDOB: Aldoase5. TPI 1: Triose phosphate isomerase6. GAPD: Glyceraldehyde 3-phosphate
dehydrogenase7. PGK 1: Phosphoglycerate kinase8. PGAM 1: Phosphoglycerate mutase9. ENO 1: Enolase10. PKLR: Pyruvate kinase
Glycolytic pathway
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020406080
100120140160180200
6 h 12 h 16 h 20 h
Treatment Time
Cel
l pro
lifer
atio
n (%
of c
ontro
l)Untreated-Control SW-480 cell line treated with 15 mM D-(+)-Glucose SW-620 cell line treated with 15 mM D-(+)-Glucose
Cell proliferation by D-(+)-glucose
SW480 cell: the viability values were 25, 49, 56, and 68%SW620 cell: the viability values were 32, 52, 67, and 78%
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Activation of Activation of glycolysisglycolysis by by DD--(+)(+)--glucoseglucose
SW480 cell line SW480 cell line SW620 cell line SW620 cell line
TimesTimesConcentration (mg/dl) Concentration (mg/dl) Increase (%) Increase (%) p*p* Concentration Concentration
(mg/dl) (mg/dl)
Increase (%) Increase (%) p* p*
6 h 6 h 20.39 20.39 ±±
0.06 0.06 3.25 3.25
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KEGG Pathway
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JawJaw--Yuan WangYuan Wang
KEGG Pathway
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JawJaw--Yuan WangYuan Wang
Hypoxia Chamber
Normoxia( 5% CO2 and
21% O2)
Hypoxia (1% O2,5% CO2
and 94% N2)
Hypoxicrelated-genes
Glycolyticrelated-genes
Molecular Mechanism in Colorectal Cancer
SW480 cell&
SW620 cell
24 hrs & 48 hrs
Tumor tissue
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JawJaw--Yuan WangYuan Wang
Hypoxia(Hypoxia(缺氧缺氧))與乳酸與乳酸(lactate)(lactate)關聯性的分析結果關聯性的分析結果
SW480 cell lineSW480 cell line24 hrs24 hrs: : 2.242.24倍倍48 hrs: 3.3648 hrs: 3.36倍倍
SW620 cell lineSW620 cell line24hrs: 3.0624hrs: 3.06倍倍48 hrs: 3.1748 hrs: 3.17倍倍
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JawJaw--Yuan WangYuan Wang
HIFHIF--11αα和和GLUT1GLUT1基因一致性基因一致性 表現的分析結果表現的分析結果
HIFHIF--11αα
Gene expression Gene expression ratioratio 1.02 1.36 1.08 1.26 1.76 1.23 1.871.02 1.36 1.08 1.26 1.76 1.23 1.87 6.37 2.42 2.25 7.63 2.306.37 2.42 2.25 7.63 2.30
GLUT1GLUT1
Gene expression Gene expression ratioratio 1.89 2.37 1.91 1.86 2.48 1.79 1.1.89 2.37 1.91 1.86 2.48 1.79 1.98 3.89 2.34 2.32 4.43 2.5898 3.89 2.34 2.32 4.43 2.58
ββ--actinactin
SW480 cell24 hrs
SW620 cell24 hrs
SW480 cell48 hrs
SW620 cell48 hrs
120 bp
168 bp
245 bp
Contr
ol
Hypo
xia
Norm
oxia
Contr
ol
Hypo
xia
Norm
oxia
Contr
ol
Hypo
xia
Norm
oxia
Contr
ol
Hypo
xia
Norm
oxia
HIF-1α和GLUT1基因呈現一致性的上升表現
Results: (2)
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JawJaw--Yuan WangYuan Wang
比較比較SW480SW480和和SW620SW620細胞株其細胞株其HIFHIF--11αα基基 因表現情形因表現情形
SW480 cell lineSW480 cell line24 hrs: 24 hrs: 1.261.26倍倍48 hrs: 48 hrs: 2.632.63倍倍
SW620 cell lineSW620 cell line24hrs: 24hrs: 1.431.43倍倍48 hrs: 48 hrs: 3.323.32倍倍
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JawJaw--Yuan WangYuan Wang
比較比較SW480SW480和和SW620SW620細胞株其細胞株其GLUT1GLUT1基基 因表現情形因表現情形
SW480 cell lineSW480 cell line24 hrs: 24 hrs: 1.241.24倍倍48 hrs: 48 hrs: 1.661.66倍倍
SW620 cell lineSW620 cell line24hrs: 24hrs: 1.391.39倍倍48 hrs: 48 hrs: 1.721.72倍倍
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Genes with altered expression Genes with altered expression levels in CRC were mainly levels in CRC were mainly
associated with fatty acid and associated with fatty acid and glucose metabolic pathways, in glucose metabolic pathways, in
addition to hypoxic pathway addition to hypoxic pathway speculated to have an important speculated to have an important
role linked to carcinogenesis role linked to carcinogenesis
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JawJaw--Yuan WangYuan Wang
Thank You For Your AttentionThank You For Your Attention
投影片編號 1Cancer投影片編號 3投影片編號 4投影片編號 5投影片編號 6投影片編號 7投影片編號 8投影片編號 9The 2 main types of genes are playing a role in cancer are oncogenes and tumor suppressor genes 投影片編號 11Functional Properties of Oncogenes Products of Oncogenes Oncogene Activation 投影片編號 15投影片編號 16投影片編號 17投影片編號 18投影片編號 19投影片編號 20投影片編號 21投影片編號 22投影片編號 23投影片編號 24投影片編號 25投影片編號 26投影片編號 27投影片編號 28投影片編號 29投影片編號 30投影片編號 31投影片編號 32投影片編號 33投影片編號 34投影片編號 35投影片編號 36投影片編號 37投影片編號 38投影片編號 39投影片編號 40投影片編號 41投影片編號 42投影片編號 43投影片編號 44投影片編號 45投影片編號 46投影片編號 47投影片編號 48投影片編號 49投影片編號 50投影片編號 51投影片編號 52投影片編號 53投影片編號 54Possible invasion and metastasis-associated genesGenes are demonstrated to be considerably correlated to tumor invasion and metastasis 投影片編號 57投影片編號 58投影片編號 59Functional categories of up-regulated or down-regulated genes in Colorectal Cancer投影片編號 61投影片編號 62投影片編號 63投影片編號 64投影片編號 65投影片編號 66投影片編號 67投影片編號 68投影片編號 69投影片編號 70投影片編號 71投影片編號 72投影片編號 73Activation of glycolysis by D-(+)-glucose投影片編號 75投影片編號 76投影片編號 77投影片編號 78Hypoxia(缺氧)與乳酸(lactate)關聯性的分析結果 HIF-1α和GLUT1基因一致性表現的分析結果比較SW480和SW620細胞株其HIF-1α基因表現情形 比較SW480和SW620細胞株其GLUT1基因表現情形 Genes with altered expression levels in CRC were mainly associated with fatty acid and glucose metabolic pathways, in addition to hypoxic pathway speculated to have an important role linked to carcinogenesis Thank You For Your Attention�