carcinogenesis dan nomenclature edit.ppt

8/16/2019 CARCINOGENESIS DAN NOMENCLATURE edit.ppt

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Chemical Carcinogenesis

Experiment! m"#e!$ N"rm! Ce!!%

INITIATION

PROMOTION

Cn&er Ce!!%

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Inititi"n(pr"m"ti"n %&)eme

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INITIATION

• Initit"r !"ne i% n"t %+,&ient -"r t+m"r-"rmti"n .Gr"+p /0

• Inititi"n re%+!t% -r"m exp"%+re "- &e!!%

t" n ppr"prite #"%e "- initit"r.&r&in"1eni& 1ent%0

• Inititi"n irreer%i3!e m+tti"n .DNA#m1e0 mem"r4 m"nt)% !ter

5pr"m"ter t+m"r .Gr"+p 26'0

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PROMOTER

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9 N"n(t+m"ri1eni& 34 it%e!- 9 In#+&e t+m"r% in initite# &e!!% .Gr"+p70

9 :)en pr"m"ter i% pp!ie# 3e-"reinitit"r; n"

t+m"r #ee!"pe# .Gr"+p *09 :)en t)e time 3et


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M>"r C)emi&! Cr&in"1en

Direct-acting Carcinogens• A!?4!tin1 A1ent%• A&4!tin1 1ent%

Procarcinogen that Require Metabolicactivation• P"!4&4&!i& 6 Heter"&4&!i& Ar"mti& H4#r"&r3"n%• Ar"mti& Amine%; Ami#e%; A@" D4e%• Nt+r! P!nt n# Mi&r"3i! Pr"#+&t%

• Ot)er%

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Inititi"n "- Cr&in"1ene%i%

/ Dire&t &tin1 &"mp"+n# #" n"t re+ire&)emi&! trn%-"rmti"n -"r t)eir&r&in"1eni&it4

2 In#ire&t &tin1 &"mp"+n# pr"&r&in"1en;

re+ire met3"!i& &"ner%i"n in i" t"pr"#+&e +!timt &r&in"1en

Pr"pert4 in &"mm"n$

T)e4 re )i1)!4 re&tie e!e&tr"p)i!e% t)t&n re&t


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Cr&in"1en t+m"r t4pe% (fngerprinting)

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Events in ChemicalCarcinogenesis


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Pr"m"ti"n "- Cr&in"1ene%i%

• Pr"m"ter%$ p)"r3"! e%ter%; )"rm"ne; p)en"!%;#r+1%

• N"t m+t1eni& )"< #" t)e4 &"ntri3+te t"t+m"ri1ene%i% %t+#4 "- TPA

• TPA$ ( p)"r3"! e%ter%

( p"


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Inititi"n

6Pr"m"ti"n

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Inititi"n 6 pr"m"ti"n

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R#iti"n Cr&in"1ene%i%

• Trn%-"rm !! ?in# "- &e!!% in itr" n# in#+&ene"p!%m% in i"; in )+mn 6 experiment! nim!

• UV !i1)t %?in &n&er

• I"ni@in1 r#iti"n "- me#i&!; "&&+pti"n!; n#3"m3 "- "ri1in% pr"#+&e riet4 "- m!i1nntne"p!%m%

• T)e e=e&t "- UV !i1)t i% %"me


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UV

• UV e=e&t% "n &e!!% in)i3iti"n "- &e!! #ii%i"n;in&titi"n "- en@4me%; in#+&ti"n "- m+tti"n;n# ?i!!in1 t)e &e!!%

• UV t4pe$

( UVA .'2 * nm0$ n"n(m+t1eni&

( UVB .2 '2 nm0$ m+t1en; n"t !tere# 34"@"ne

( UVC .2 2 nm0$ m+t1en; !tere# 34 "@"ne

• T4pe "- &n&er re%+!t% re %?in &n&er%$ SCC; BCC;

me!n"m• UVB !%" &+%e% m+tti"n in "n&"1ene% .ras0 n#t+m"r %+ppre%%"r 1ene% . p530

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The carcinogenicity of UVB is attributed to itsformation of pyrimidine dimers in DNA

T)i% DNA #m1e i% repire# 34 NER .n+&!e"ti#eex&i%i"n repir0

/ Re&"1niti"n "- t)e DNA !e%i"n

2 In&i%i"n "- t)e #m1e %trn# "n 3"t) %ite% "- t)e

!e%i"n

' Rem"! "- t)e #m1e n+&!e"ti#e

* S4nt)e%i% "- n+&!e"ti#e pt&)

7 S4nt)e%i% "- it% !i1ti"n

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NER .n+&!e"ti#e ex&i%i"n

repir0• T)i% pr"&e%% nee#% t !e%t t)e pr"#+&t "- 2 1ene%

• P"%t+!ti"n$ ex&e%%ie %+n exp"%+re &p&it4 "-NER pt)


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I"ni@in1 R#iti"n

• E!e&tr"m1neti& r#iti"n

( (r4% n# 1mm r4%

• Prti&+!te r#iti"n( prti&!e%; β prti&!e%; pr"t"n; ne+tr"n

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Hierr&)4 "- V+!ner3i!it4

/ Le+?emi

2 T)4r"i#

' Bre%t; !+n1; %!ir4 1!n# .interme#ite0* S?in; 3"ne; 1%tr"inte%tin! tr&t .re!tie!4 re%i%tnt0

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CARCINOGENESIS$ T)e M"!e&+!r 3%i% "- Cn&er

• N"n!et)! 1eneti& #m1e !ie% t t)e )ert "-&r&in"1ene%i%

• ' &!%%e% "- n"rm! re1+!t"r4 1ene%$ 1r"


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08/17/03 TUMs-PAFKUGM 2/


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Per+3)n -en"tipi?

• Si-t pert+m3+)n

( !ep% #ri ?"ntr"!

( ?e11!n mt+r%i

( trn%p!nt3!e

( imm"rt!

• Per+3)n m"r-"!"1i?

• Kri"tipi?

• Anti1eni?

• Dei%i met3"!i?• Mem3rn %e!

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AKTIVASI ONKOGENA

Mechanism by which protooncogenes aretransformed into oncogenes

• C)n1e% in t)e %tr+&t+re "- t)e 1ene 3n"rm!1ene pr"#+&t ."n&"pr"tein0

( P"int m+tti"n%

( In%erti"n n# #e!eti"n

• C)n1e% "- re1+!ti"n$ 1ene expre%%i"n en)n&e# inppr"prite pr"#+&ti"n "- t)e%tr+&t+r!!4 n"rm! 1r"


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Point Mutation• ras "n&"1ene t)e 3e%t exmp!e

• A er4 !r1e n+m3er "- )+mn t+m"r% &rr4 r%p"int(m+tti"n%

• M+tti"n =e&t #"min &riti&! t" t)e GAP(in#+&e# )4#r"!4%i% "- GTP m+tnt r% pr"tein%

)e re#+&e# 3i!it4 t" )4#r"!4@e GTP• Fre+en&4$

( J$ pn&reti& #en"&r&in"m

( 7$ &"!"n n# t)4r"i# &n&er

( '$ !+n1 #en"&r&in"m 6 m4e!i# !e+?emi( $ m"%t "ri! n# 3re%t t+m"r%

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Model for Action of ras gene



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Chromosomal

translocations


B+r?ittQ% !4mp)"m

C)r"ni& M4e!"1en"+%Le+?emi


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ene Ampli!cation


• Amp!i&ti"n "- N(myc 1ene in ne+r"3!%t"m$#"+3!e min+te% HSR.H"m"1en"+%(%tinin1

re1i"n0


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CLASSIFICATION

A" #he cell type origin $typing% / A#en" 1!n# &e!!

Fi3r" 3r"3!%t

O%te" "%te"3!%t

M4" m+%&!e &e!!

L4mp)"m !4mp)"i# &e!!

Le+?emi 3!"# &e!!


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!ei"m4"mfolicular adenoma


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2 Cr&in"m epit)e!i! Sr&"m me%en&)4m!

B!%t"m 3!%t .&e!!0 L4mp)"m !4mp)"i#

Le+?emi 3!""# &e!!


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3!%t"msarcoma


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&" Clinical and histologicalbehaviour

/ A#en"m ( #en"&r&in"m

Fi3r"m ( 3r"%r%"m O%te"m ( "%te"%r&"m

M4"m ( m4"%r&"m

et&


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!ei"m4"%r&"mosteosarcoma


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'" Malignant tumor

&e!! t4pe "ri1in &n 3e re&"1ni@e#34

a" (peci!c cell product

M+&ine $ #en"&r&in"m Kertine $ %+m"+% &e!!&r&in"m

Me!nine $ me!n"m Reti&+!in?"!1en $3r"%r&"m


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me!n"mpearl formation


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b" (peci!c cell structure

T"n"3ri! $ %+m"+% &e!! &r&in"m M4"3ri! $ m4"%r&"m

c" (peci!c histological structure T+3+!r $ #en"&r&in"m Trn%iti"n! epit)e! $ trn%iti"n!&r&in"m

G!"mer+!i !i?e $ nep)r"3!%t"m


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1!"mer+!i !i?etransitional


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d" rade of di)erentiation / :e!! #i=ererentite#

2 M"#erte #i=erentite#

' P""r!4 #i=erentite# * Un#i=erentite#np!%ti&


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C" *rgan or tissue origin :D %+m"+% &r&in"m3r"n?)+%

PD %+m"+% &e!! &r&in"m&eri?

:D #en"&r&in"m

en#"metri+m et&


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D" #he volume comparationbetween parenchym and stroma

/ Me#+!!r4 &r&in"m pren&)4m %tr"m %"-t

&"n%i%ten&4

2 Simp!ex &r&in"m pren&)4m %tr"m $ %imi!r

"!+me

' S&irr)"+% &rin"m

pren&)4m %tr"m )r#&"n%i%ten&4


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E" Macroscopic aspect +" &enign epithelial tumor

Ppi!!"m 3 P"!4p

& C4%t

'" Carcinoma

Ppi!!"mt"+%

3 U!&erte#

& Di=+%e in!trte# !in itis p!%ti&


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M,ED #.M*Rmixe# "- 2 "r m"re t+m"r &e!!t4pe

( A#en"3r"m( Cr&in"%r&"m

( Me%en&)4m ( e+t"p


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3r"#en"m


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/AMAR#*MA!"&! mi%-"rmti"n ti%%+e


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#.M*R *1 EM&R2*0A3 #,((.ERE(#

C)"r# #"r%!i% $ &)"r#"m

S&) "- Rt)?e $ &rni"p)r4n1i"mEnme! "r1n $ me!!"3!%t"m#mntin"m


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#mntin"m


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EM&R2*0A3 #.M*R

&"n1enit! t+m"r

+" 0euroblastoma ( S4mpt)i&"3!%t"m

( Me#+!!"3!%t"m

( Retin"3!%t"m

S4n#r"me Pepper $ ne+r"3!%t"m "-%+prren! 1!n# met%t%i% int)e 3#"min! !4mp)n"#e n#!ier

n#

S4n#r"me n /utchinson $ 3%i% %?+!!met%t%i%

'" 0ephroblastoma


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#ERA#*MA

t+m"r "- )eter"t"pi& ti%%+e e!ement m"re t)n "ne#erm"3!%t

#eratogenesis/ P!+rip"tent &e!!% em3r4"n! %t1e %eprte# n#

i%"!te# +n%+&&e%-+! t


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Tert"m i% #i=erent


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tert"m


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#umor with specialnomenclature

A" onade tumor / Semin"m $ m!i1nnt 1erm &e!! t+m"r

L"&ti"n $ te%ti&!e

"r4 $ #4%1ermin"m 2 Grn+!"% &e!! t)e& &e!! t+m"r "ri! %tr"m!

t+m"r

Gr+!"% &e!! t+m"r

T)e&"m

M"%t "- t)em 3eni1n


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seminomaGranulosa celltumor


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&" Placenta tumor +" Mola hydatidosa Beni1n; tr"p)"3!%ti& t+m"r

M"!e )4#ti# 1rpe -r+it -"rm

N" -et+%

E#emt"+% %tr"m


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'" Choriocarcinoma

M!i1nnt; tr"p)"3!%ti& t+m"r


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C NERVE SYSTEM TUMOR


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C NERVE SYSTEM TUMOR

+" Central nerve system

G!i &e!!% 1!i"m A%tr"&4t %tr"&4t"m

!"&! m!i1nnt; +n&p%+!te#

%+r1i&! ex&iti"n $ #i,&+!t

Me#+!!"3!%t me#+!!"3!%t"m

'" Peripheral nerve system

S&)


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peri-er nere t+m"rastrocytoma


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' Me%"t)e! "- r&)n"i#

( menin1i"m 3eni1n

( ne%t "- me%"t)e! in 3r"+% %tr"m ( m!i1nnt me%"t)e!i"m

D" #.M*R *1 #/E (ER*.(

MEM&RA0E Me%"t)e! p!e+r n# perit"ne+m

( me%"t)e!i"m

( 3eni1n rint !"&! t+m"r

( m!i1nnt rint in!trtie m%%t+m"r in p!e+r n#perit"ne+m

E H ti # ! ) i# ti


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E Hem"p"eti& n# !4mp)"i# ti%%+e RES $ m!i1nnt reti&+!"%i%

/ Le+?emi

2 Hemt"%r&"m

+" 3eu4emia $ )em"p"eti& &e!!% t+m"r

Sp"ntne"+% m+!tip!e !"&ti"n

3"ne mrr"


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'" /ematosarcoma

in%iene%% "- )em"p"eti& &e!!%; 3+t

"-ten !"&! &ir&+m%&ri3e# 1r"


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+" 3E.5EM,A

&e!!% "ri1in $ m4e!"&4t; !4mp)"i#;er4t)r"3!%t; me1?r4"&4t;

m"n"&4t; p!%m &e!!% m"%t -re+ent $ !4mp)ti& n#

m4e!"i#

t


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c" Acute myeloid

T)e in!trtie &e!!% $ m4e!"3!%t 6 pr"m4e!"&4t

In&i#en&e $ !! 1e%

d" Chronic myeloid

T)e in!trtie &e!!% $ m4e!"&4t

In&i#en&e $ !! 1e%

A3n"rm! in %m!! &)r"m"%"me $ P)i!#e!p)i P)/ &)r"m"%"me


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'" /EMA#*(ARC*MA

T)e m"%t p"p+!r $

a" 0on /odg4in6 lymphoma $ B &e!!%

T &e!!%

/ Sm!! &e!!%

2 Interme#ite

' Lr1e &e!!%

* Anp!%ti& !r1e &e!! !4mp)"m .ALCL0


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b" /odg4in6 lymphoma

( P!e"m"rp)i%me

( Stern3er1(Ree# &e!!%

c" +" Multiple myeloma m"r3+% K)!er

'" Plasmacytoma

P!%m3!%t pr" p!%m&4t

&,*3*2 *1 #.M*R R*7#/


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&,*3*2 *1 #.M*R R*7#/

• T)e t+m"r &e!!% ten# t" rep!i&te rt)er t)nt" #i=erentite #+e t" 1eneti& !terti"n%."n&"1ene &titi"n; nti("n&"1ene%+ppre%%i"n; et&0

• M"%t t+m"r% re "- m"n"&!"n! "ri1in

• In&re%in1 in t)e pr"p"rti"n "- %tem &e!!%+n#er1"in1 rep!i&ti"n; n# &"rre%p"n#in1#e&re%e in t)e pr"p"rti"n pr"1re%%in1 t" -+!!en#(%t1e mt+rti"n

• ' -&t"r% in+en&in1 re$ 1r"


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An1i"1ene%i%

TUMs-PAFKUGM

(chematic representation of tumor


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(chematic representation of tumorgrowth8 growth fraction

TUMs-PAFKUGM

#umor Progression and


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#umor Progression and/eterogeneity

TUMs-PAFKUGM


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In%i"n Se+en&e "- B%ementMem3rne 34 T+m"r Ce!!%

TUMs-PAFKUGM


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T)e

METASTATICCASCADE

TUMs-PAFKUGM

T.t+m"r0N.n"#+!e0M.met%t%i%0


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T.t+m"r0N.n"#+!e0M.met%t%i%0

TUMs-PAFKUGM

PERBEDAAN ANTARA TUMOR JINAK DAN TUMOR GANAS


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TUMs-PAFKUGM

Karakteristik Tumor jinak Tumor ganas

Diferensiasi/

anaplasi

Diferensiasi baik, struktur samadengan struktur jaringan asal

Difernsiasi tidak ada, dengananaplasia; struktur sering atipi

Kecepatan pertumbuhan

Biasanya progresif - lambat; bisa menjadi stasioner atauregresi; tidak ada gambarannitosis patologik

Bervariasi dari lambat sampaicepat, sering banyak mitosis

patologik

nvasi lokal Biasanya kohesif danekspansif; batas tegas;sentrifugal

nvasif lokal, infiltratif ke jaringan sekitar!

"etastasis #idak ada $ering terjadi; makin besar danmakin jelek diferensiasinyamakin sering terjadi metastasis

$impai Bersimpai #idak bersimpai

%eaksi radang &arang terjadi $ering terjadi

Kematian 'ampir tidak pernah terjadi 'ampir selalu terjadi

TUMOR IMMUNITY


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TUMOR IMMUNITY

0ormal cell

Geneti& !terti"n

Ne"p!%ti& trn%-"rmti"n

Expre%%i"n "- %+r-&e nti1en%

N"n(%e!- nti1en

,nduce tumor surveillance

TUMs-PAFKUGM


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TUMOR IMMUNITY

Questions:

/ :)t i% t)e nt+re "- t+m"r nti1en%

2 :)t )"%t e=e&t"r %4%tem% m4re&"1ni@e t+m"r &e!!%

' I% ntit+m"+r imm+nit4 e=e&tie1in%t %p"ntne"+% ne"p!%m%

* Cn imm+ne re&ti"n% 1in%t t+m"r%3e exp!"ite# -"r imm+n"t)erp4

TUMs-PAFKUGM


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T+m"r nti1en

Tumor antigenicity is usually assessed by:

• The ability of an animal to resist a live tumor implant afterprevious immunization with live or killed tumor cells

•The ability of tumor free host animals to resist challenge when infused with sensitized T cells from a tumor-immunized syngeneic donor

• The demonstration in vitro of tumor cells destruction by

cytotoxic CD8+ T cells derived from a tumor-immunizedanimal

TUMs-PAFKUGM


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T+m"r nti1en

#(o broad categories)

TSA% .T+m"r Spe%i& Anti1en%0

TAA% .T+m"r A%%"&ite# Anti1en%0

TUMs-PAFKUGM


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T+m"r nti1en%

TSA% .T+m"r Spe&i& Anti1en%0• Pre%ent "n!4 "n t+m"r &e!!% n"t "n n4n"rm! &e!!%

• Derie# -r"m pepti#e% t)t re +ni+e!4

pre%ent


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T+m"r nti1en

TSA .T+m"r Spe%i& Anti1en0

A Ti%%+e(%pe&i& %)re#nti1en

B Anti1en re%+!tin1 -r"mm+tti"n

C Vir! nti1en TAA .Ti%%+e A%%"&ite# Anti1en0

D Ti%%+e %pe&i& nti1en

E Oerexpre%%e# nti1en

F On&"-et! nti1enG Di=erentiti"n nti1en

TUMs-PAFKUGM

T+m"r Spe&i& Anti1en%


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TUMs-PAFKUGM

A"#issue-speci!c shared antigen

- En&"#e# 34 1ene% t)t re %i!ent in irt+!!4 !! n"rm! #+!t ti%%+e%

- 3+t expre%%e# in n+m3er "- t+m"r% "- ri"+% )i%t"!"1i& t4pe%

- Te%ti% .n" HLA0$ t)e "n!4 n"rm! "r1n in


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TUMs-PAFKUGM

&" Antigen resulting frommutation

• M+tte# pr"t"("n&"1ene n# t+m"r

%+ppre%%"r 1ene• P7'; K(r%; CDK*; 3&r(&(3!

T+m"r Spe&i&


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T+m"r Spe&i&Anti1en%

TUMs-PAFKUGM

C" 9iral antigens

• Anti1en% #erie# -r"m

"n&"1eni& ir+%e%• E pr"tein "- HPV(/8

Ti%%+e A%%"&ite# Anti1en


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Ti%%+e A%%"&ite# Anti1en

TUMs-PAFKUGM

D" #issue speci!c antigen

• S)re# 34 t+m"r &e!!% n# t)eir n"rm!

+ntrn%-"rme# &"+nterprt%• Me!n"&4te% n# me!n"m &e!!% 3"t) expre%%t4r"%in%e

Ti%%+e A%%"&ite# Anti1en%


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TUMs-PAFKUGM

E" *vere:pressed antigen

• C(er3B2 .ne+0$ "erexpre%%e# in ' "- 3re%tn# "rin &n&er


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1" *ncofetal antigens

• N"rm!!4 expre%%e# in em3r4"ni&ti%%+e

• AFP$ A!p) Fet"pr"tein

• CEA$ Cr&in"em3r4"ni& nti1en

TUMs-PAFKUGM


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Ti%%+e A%%"&ite# nti1en%

" Di)erentiation antigen

• Pe&+!ir t" t)e #i=erentiti"n %tte t


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Antit+m"r E=e&t"r Me&)ni%m%

TUMs-PAFKUGM

ADCC

Ce!!+!r e=e&t"r% t)t me#ite


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Ce + e e& " % e# eimm+nit4

C4t"t"xi& T !4mp)"&4te%

• Pr"te&tie r"!e 1in%t ir+%(%%"&ite# t+m"r%EBV; HPV .p"%%e%%in1 MHC &!%% /0

Nt+r! ?i!!er &e!!% .NK &e!!%0

• L4mp)"&4te% &p3!e "- #e%tr"4in1 t+m"r &e!!%


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IMMUNOSURVEILLANCE

F&t%$In&re%e# "&&+rren&e "- t+m"r%

In imm+n"#e&ient )"%t

Imm+n"%+rei!!n&e

.it i% n"t per-e&t0

TUMs-PAFKUGM

Me&)ni%m% t" e%&pe -r"m


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p T+m"r Imm+n"%+rei!!n&e

/ Se!e&tie "+t1r"


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CA0CER (.PPRE((*R E0E(

• Mi%n"mer

• P)4%i"!"1i& -+n&ti"n$ re1+!te &e!! 1r"


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S+3(&e!!+!r !"&ti"n "- pr"tein pr"#+&t"- t+m"r %+ppre%%"r 1ene%

2 broad categories regarding the functions:M"!e&+!e% t)t re1+!te n+&!er trn%&ripti"nn# &e!! &4&!e

• Ce!! %+r-&e$ TGF(re&ept"r; E(&#)erin• Un#er p!%m me3rne$ NF(/• C4t"%?e!et"n$ NF(2• C4t"%"!$ APCM"!e&+!e% t)t re1+!te %i1n! trn#+&ti"n

• N+&!e+%$ R3; p7'; :T(/; p/8.INK*0; BRCA(/;BRCA(2

21/05/16 pafkugm J/

CANCER SUPPRESSOR GENES


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CANCER SUPPRESSOR GENES

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T)e &entr! r"!e "- t)e pRB in


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pre1+!tin1 t)e &e!! &4&!e

21/05/16 pafkugm J'

S ! t # t i ! #


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Se!e&te# t+m"r(%+ppre%%"r 1ene in"!e#in )+mn ne"p!%m

#*+-β receptor

• F+n&ti"n$ Gr"


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pp 1in )+mn ne"p!%m

-cadherin

• +unction)

Ce!! #)e%i"n

• #umors associated (ith somatic mutation)

C 1%ter 6 3re%t

• #umors associated (ith inherited mutation)

Fmi!i! 1%tri& &n&er

21/05/16 pafkugm J7

Se!e&te# t+m"r(%+ppre%%"r 1ene


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pp 1in"!e# in )+mn ne"p!%m

+-.

• +unction)

In)i3iti"n "- ras %i1n!trn%#+&ti"n


S&)


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Se!e&te# t+m"r %+ppre%%"r 1ene in"!e#in )+mn ne"p!%m

+-• +unction)

Un?n"


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pp 1in )+mn ne"p!%m

012• +unction)

In)i3iti"n "- %i1n! trn%#+&ti"n


C "- %t"m&); &"!"n; pn&re%Xme!n"m


Fmi!i! A#en"mt"+% P"!4p"%i% &"!iX

&"!"n &n&er

21/05/16 pafkugm J



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%b

• +unction)

Re1+!ti"n "- &e!! &4&!e


Retin"3!%t"m; "%te"%r&"m;

C 3re%t; &"!"n; !+n1


Retin"3!%t"m; "%te"%r&"m

21/05/16 pafkugm JJ



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p34• +unction)

Re1+!ti"n "- &e!! &4&!e 6 p"pt"%i% inre%p"n%e

t" DNA #m1e• #umors associated (ith somatic mutation)

C 1%ter 6 3re%t


Li(Fr+meni %4n#r"me

M+!tip!e &r&in"m n# %r&"m

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Se!e&te# t+m"r %+ppre%%"r 1enein"!e# in )+mn ne"p!%m

5#-.

• +unction)

N+&!er trn%&ripti"n


:i!m% t+m"r


:i!m% t+m"r

21/05/16 pafkugm //

Se!e&te# t+m"r(%+ppre%%"r 1ene in"!e#


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pp 1in )+mn ne"p!%m

p16 6K-7a8

• +unction)

Re1+!ti"n "- &e!! &4&!e 34in)i3itin1 CDK


Pn&reti&; e%"p)1e! &n&er


Me!n"m

21/05/16 pafkugm /2

Se!e&te# t+m"r(%+ppre%%"r 1ene in"!e# in) !


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)+mn ne"p!%m

B%20-.

• +unction)

DNA repir


Un?n"


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pp 1in )+mn ne"p!%m

B%20-

• +unction)

DNA repir


Un?n"


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inte1rit4 "- t)e 1en"me

21/05/16 pafkugm /7

Apoptosis


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Apoptosis.pr"1rmme# &e!! #et)0

Intern!!4 pr"1rmme# n# &""r#inte# #et) !"%%"- %in1!e &e!!% %pre# m"n1 )e!t)4 &e!!%;

in -"rm "- &e!! #et) #e%i1ne# t" e!iminte+n


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Gene% t)t Re1+!te Ap"pt"%i%

bcl-2 amily:

Ant1"ni%t%

bcl-2 and bcl-xL

A1"ni%t%

bax, bcl-xS, bad, bid

21/05/16 pafkugm /


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Regulation of cell death

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Biological Mechanism


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Biological Mechanism

/ Si1n!in1 pt)


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21/05/16 pafkugm //

APOPTOSIS


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APOPTOSIS

21/05/16 pafkugm ///

Mit"&)"n#ri! eent% n# t)e e=e&t% "-3&! 2 in p"pt"%i%


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3&!(2 in p"pt"%i%

21/05/16 pafkugm //2

T)e r"!e "- p"pt"%i%1 Growth an development


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1. Growth an development

( Em3ri"1ene%i%$ imp!ntti"n; "r1n"1ene%i%;#i=erentiti"n; in"!+ti"n

2. Homeostatic mechanism to maintain cell populationin tissue

( )"rm"ne #epen#ent in"!+ti"n

( pr"!i-ertie &e!!% p"p+!ti"n$ inte%tin! &r4pt epi)te!

3. Defense mechanism

( ne+tr"p)i!% #et) #+rin1 n &+te inmmt"r4 re%p"n%e ( &e!! #et) in#+&e# 34 &4t"t"xi& T &e!!%$ in &e!!+!r imm+ne

re>e&ti"n

4. When cells are damaged by disease or noious agent

( ir+% in-e&ti"n$ )eptiti% C"+n&i!mn 3"#ie%

( !"< #"%e% in>+ri"+% %tim+!i$ )et; r#iti"n; nti(&n&er#r+1%; )4p"xi

!. "ging process

21/05/16 pafkugm //'

MORPHOLOGY


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• Ce!! %)rin?1e• C)r"mtin &"n#en%ti"n• F"rmti"n "- &4t"p!%mi& 3!e3% n#p"pt"ti& 3"#ie%

• P)1"&4t"%i% "- p"pt"ti& &e!!% 34#>&ent )e!t)4 &e!!% .pren&)4m!&e!!% "r m&r"p)1e%0

• Int&t p!%m mem3rne #+rin1

p"pt"%i%

21/05/16 pafkugm //*

MORFOLOGI ultrastructural change sequences

0ECR*(,( ; AP*P#*(,(


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0ECR*(,( ; AP*P#*(,(

21/05/16 pafkugm //7

APOPTOSIS$ gambaran ultrastruktur


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21/05/16 pafkugm //8

Apoptosis pada 4ulit denganrea4si imun


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rea4si imun

21/05/16 pafkugm //

Biochemical features


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Pr"tein C!e1e

• Spe&i&$ pr"tein )4#r"!4%i% in"!in1 t)e&titi"n "- %eer! mem3er% "- &4%teinpr"te%e .&%p%e0

Pr"tein &r"%%(!in?in1• Trn%1!+tmin%e &titi"n$ p"pt"ti& 3"#ie%DNA 3re?#"


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E!e&tr"p)"re%i% "- t)eDNA extr&te#i -r"m

&e!! &+!t+re+n#er


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• Si1n!!in1 34 re&ept"r% -r"m T+m"r

Ne&r"%i% F&t"r .TNFR0 -mi!4( Ap"pt"%i% #ime#i%i "!e) Fas-Fas ligand(FasL / CD95L)

• Ap"pt"%i% in#+&e# 34 TNF

( CTL %tim+!te# Ap"pt"%i%

( Ap"pt"%i% -ter 1r"


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caspase activation< and deathsignal induction

21/05/16 pafkugm /2/

Model: "#F recetor mediated signal and aotosisinduction : p"pt"%i% % %+ri! in#+&e#


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induction : p"pt"%i% % %+ri! in#+&e#34TNF

21/05/16 pafkugm /22

KESIMPULAN


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• Ap"pt"%i% i% n imp"rtnt p)4%i"!"1i&! pr"&e%% in t)e3"#4

carcinogenesis dan nomenclature edit.ppt

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