Dasar Dasar Onkologi
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KARSINOGENESIS
SASARAN GENETIK KARSINOGENESISSASARAN GENETIK KARSINOGENESIS
Bahan Bahan Fisiko-kimiaFisiko-kimia
VirusVirusonkogenikonkogenik
Sasaran utama:Sasaran utama:Mutasi DNA/gen regulatorMutasi DNA/gen regulator
siklus /pertumbuhan siklus /pertumbuhan selsel
TRANSFORMASI SELTRANSFORMASI SEL
Faktor endogenFaktor endogenOxidant stressOxidant stress
ONKOGENESISONKOGENESIS
Growth promotingGrowth promotingoncogenesoncogenes
Tumor suppressorTumor suppressorgenesgenes
TransformationTransformationUncontrolled growth,Uncontrolled growth,Abn biol behaviourAbn biol behaviourMaturation arrestMaturation arrest
Abnormal diffAbnormal diff
Activation/Activation/amplificationamplification
MutationsMutations
InactivationInactivation
MutationsMutations
CONTOH PERUBAHAN GENETIK DAN EPIGENETIK PADA KARSINOGENESISPerubahan Gen terkena Akibat Jenis
kankerTranslokasi bcr dan abl Fusion protein CML & ALL
Homoz deletion NF1 Deregulated p21 Neurofibrosarc
Frameshift mut APC Disfungsi TSG Kolorektal
Amplifikasi gen EGFR Aktivasi autokrin Banyak
Substitusi single base
P53 Kontrol checkpoint hilang
Banyak
Polimorf minisa-telite
H-ras Predisposisi Ca Banyak
Simple repeat polymorh, hyper mutability
hMSH2 dan hMLH1
Instabilitas genetik
Kanker kolon SCLL
Weinstein 1995
EVOLUSI MULTISTEP KANKER KOLONEVOLUSI MULTISTEP KANKER KOLON
Epitel normal
Hiperproliferasi
Karsinoma
Late adenoma
Metastasis
Earlyadenoma
Intermedadenoma
KromosomKelainanGen
5qLossAPC
HipometilasiDNA
12pAktivasi/mutasiK-ras
18q, loss, DCC
17p, mutasi, p53
Kelainan lain
Mism
atch rep
air
DAMPAK BERBAGAI KARSINOGENDAMPAK BERBAGAI KARSINOGEN
Bahan FisikaBahan FisikaVirus onkogenikVirus onkogenik
Hbg dose-responseHbg dose-responseMutasi DNAMutasi DNAAktivasi transduksiAktivasi transduksisinyalsinyalInisiator & PromoterInisiator & Promoter
Radiasi:Ionizing, UVDose dependenceTissue specificKematian selMutasi gen spesifikAktivasi transduksisinyal
2 golongan virus:2 golongan virus:Virus DNA & retrovirusVirus DNA & retrovirusIntegrasi DNA/RNAIntegrasi DNA/RNAvirus dg gen hostvirus dg gen hostAktivasi ekspresiAktivasi ekspresionkogenonkogenDisrupsi berbagai genDisrupsi berbagai genpejamu a.l. TSGpejamu a.l. TSG
Bahan kimiaBahan kimia
MULTISTEP CARCINOGENESISMULTISTEP CARCINOGENESIS
Environment CarcinogenCarcinogen
Electroph interm
metabolism Excretion
detoxification
detoxification
Binding to DNA RNA, protein
Normal cellDNA repair
Cell death
Permanent DNA lesion
DNA replication
Preneoplastic cells
Neoplastic cells
? ?
Initiation
Promotionand
ProgressionMultiple factorsMultiple stagesMultiple genetic targets
Staging system
1. Anatomical Staging System
2. Functional Staging System
3. Combined staging System
4. Multivariate Regression Algorithm
Modalitas terapi pada kanker
1. Kemoterapi
2. Radioterapi
3. Terapi pembedahan
4. Bioterapi (BRM’s)
5. Cangkok sumsum tulang
6. Gene replacement