MASTER MINI KADATE

ENGLISH SUMMARY

T I N J A U A N P U S T A K A

CDK 167/vol.36 no.1/Januari - Februari 2009

The Food and Drug Administration and Swiss

Medical Control Agency approved cetuximab

for the irinotecan-refractory colorectal cancer.

Bevacizumab is humanized antibody that inhibit

VEGF action. The Food and Drug Administra-

tion approved the use of bevacizumab in com-

bination with any intravenous fluorouracil-

containing regimen as initial therapy for patients

with advanced colorectal cancer. There is small

gefitinib trial for colorectal cancer treatment.

CDK. 2009; 36(1) : 5-12

Epidermal Growth Factor

Receptor (EGFR) as

Therapeutic Target in

Colorectal Cancer

Santosa, C. Suharti*

Specialist Program, *Head of Hematology-Oncology

Subdept., Dept. of Internal Medicine, Faculty of

Medicine, Diponegoro University, Dr.Kariadi Hospital,

Semarang, Indonesia

Colorectal cancer is the fourth most frequent

malignant disease in the world. Estimation

of new cases and mortality are 1.023.000 and

529.000 annually. There is an increase of

colorectal cancer incidence in Indonesia, but

no exact number available.

The problems in management of colorectal

cancer are patients came in advanced stage,

refractory cytostatics regiment, adverse

reaction to cytostatics. Alternative strategy

uses an agent that act at specific site; for

instance Epidermal Growth Factor Receptor

(EGFR) inhibitor.

EGFR have specific ligand including EGF

(epidermal growth factor), bFGF (basic fibro-

blast gorwth factor), VEGF(vascular endothe-

lial growth factor) and TGF-_ (transforming

growth factor-_). They have important role in

growth dan survival of colorectal cancer.

EGFR expression in colorectal cancer is associ-

ated with aggressive disease and poor prog-

nosis. EGFR stimulates tumor growth and

progression through several mechanism i.e.

proliferation, angiogenesis, invasion, metas-

tasis, apoptosis inhibition, adhesion and

differentiation.

EGFR is specific rational target. Monoclonal

antibody (mAbs) directed against EGFR

through several mechanism: (1) extracellu-

lar binding; (2) internalization of receptor-

anti-body complexes; (3) inhibition of EGFR

signalling pathways; and (4) potential stimu-

lation of an immunological response.

Tyrosine kinase inhibitors (TKIs) directed

against EGFR through several mechanisms:

(1) intracellular binding; (2) prevention of

tyrosine kinase activation; and (3) inhibition

of EGFR signalling pathways.

There are many trials of cetuximab as EGFR

inhibitor. Cetuximab is known as IMC-25 or

C255, monoclonal antibody chimeric that

is specifically directed against EGFR.

ABSTRAK

Karsinoma kolorektal merupakan keganasan keempat di seluruh

dunia dengan perkiraan kasus baru 1.023.000 dan kematian

529.000 tiap tahun. Di Indonesia dari berbagai laporan terdapat

kenaikan jumlah kasus tetapi belum ada angka yang pasti

berapa insiden karsinoma kolorektal.

Masalah-masalah dalam pengelolaan adalah karena pasien sering

datang pada stadium lanjut, refrakter terhadap regimen sitostatika,

dan efek samping sitostatika; sehingga dikembangkan pilihan terapi

yang ditujukan pada sasaran spesifik pada Epidermal Growth Factor

Receptor (EGFR).

EGFR bersama ligand spesifiknya seperti EGF (epidermal growth

factor), bFGF (basic fibroblast growth factor), VEGF (vascular endo-

thelial growth factor), dan TGF-_(transforming growth factor-_) ber-

peran penting dalam pertumbuhan dan survival kanker kolorektal.

Ekspresi EGFR pada kanker kolorektal berhubungan dengan

agresivitas penyakit dan prognosis yang buruk. Aktivasi EGFR

menstimulasi pertumbuhan dan progresi tumor melalui beberapa

mekanisme yaitu memacu proliferasi, angiogenesis, invasi, meta-

stasis dan menghambat apoptosis, adesi dan differensiasi. Terdapat

variabilitas ekspresi atau disregulasi EGFR pada keganasan.

EGFR merupakan target rasional pada strategi antitumor. Pengem-

bangan sasaran terapi ditujukan terhadap interaksi ikatan domain

ligand ekstraseluler seperti antibodi monoklonal (mAbs) dan yang

berikatan intraseluler seperti tirosin kinase inhibitor. Antibodi

monoklonal (mAbs) bereaksi terhadap EGFR melalui mekanisme

sebagai berikut :

1. Ikatan ekstraseluler

2. Internalisasi kompleks reseptor antibodi

3. Inhibisi jalur sinyal EGFR

4. Meningkatkan stimulasi respon imunologis.

Tyrosine Kinase Inhibitor (TKIs) langsung bereaksi terhadap EGFR

melalui mekanisme aksi :

1. Ikatan intraseluler

2. mencegah aktivasi tirosin kinase

3. Inhibisi jalur sinyal EGFR.

Penelitian paling luas mengenai mAbs anti EGFR adalah cetuximab,

yang dikenal sebagai IMC-25 atau C225, suatu mAb chimeric

yang dirancang khusus menghambat EGFR. Cetuximab telah

disetujui penggunaannya oleh Food and Drug Administration

dan Swiss Medical Control Agency untuk pengobatan kanker

kolorektal yang tidak respon terhadap irinotecan. Bevacizumab

merupakan antibodi manusia yang berperan menghambat

VEGF. FDA mengakui penggunaan bevacizumab dalam kombi-

nasi dengan regimen flurouracil intravena sebagai terapi awal

kanker kolorektal lanjut. Uji klinis gefitinip untuk kanker kolorek-

tal masih terbatas.

PENDAHULUAN

Karsinoma kolorektal merupakan keganasan ke empat di seluruh

dunia dengan perkiraan kasus baru 1.023.000 dan kematian

529.000 tiap tahun.

Di Amerika Serikat menduduki urutan kega-

nasan ke tiga dan menjadi penyebab kematian ke dua terbanyak.

Pada tahun 2005 diperkirakan akan ditemukan 145.290 kasus

baru dengan kematian 56.290.

Di Indonesia dari berbagai laporan terdapat kenaikan jumlah

kasus tetapi belum ada angka pasti insiden karsinoma kolorektal.

Sjamsuhidajat (1986) dari evaluasi data di Departemen Kesehatan

mendapatkan 1,8 per 100.000 penduduk. Tirtosugondo (1986) untuk

Kodya Semarang, melaporkan peningkatan karsinoma kolorektal

dengan Age Standardized Rate (ASR) per 100.000 penduduk

untuk laki-laki tahun 1970-1974: 2,5; tahun 1980-1981: 3,2;

sementara untuk wanita tahun 1970-1974: 2,2 tahun 1982: 3,4

dan menduduki urutan ke lima di antara keganasan lain.

Modalitas terapi kanker kolorektal adalah pembedahan,

radioterapi dan kemoterapi sesuai stadium penyakitnya. Terapi

kanker kolorektal stadium dini dilakukan dengan pembedahan,

tetapi keadaan lanjut dan tidak dapat dibedah merupakan

masalah dan sering fatal. Deteksi dini merupakan suatu upaya

untuk menemukan kanker kolorektal stadium awal. Radioterapi

dan kemoterapi merupakan pilihan pada stadium lanjut.

4-10

Terapi sitostatika untuk kanker kolorektal di beberapa pusat

kanker menggunakan fluorourasil (FU), irinotecan dan obat baru

oxaliplatin. Masalah dalam pengelolaan karsinoma kolorektal

adalah refrakter terhadap regimen sitostatika dan adanya efek

samping sehingga diperlukan pilihan terapi lain.

11-15

Age Related Macular Degeneration (ARMD)

affects the central area of the retina (macula).

ARMD is the leading cause of severe irrever-

sible central vision loss. The aim of this study is

to determine the clinical characteristics of

ARMD at Cicendo Eye Hospital.

This prospective descriptive study was con-

ducted on newly diagnosed ARMD on July -

November 2005 in Cicendo Eye Hospital.

Ninety nine patients (196 eyes) consists of

45,5% males and 54,5% females, ages from

diagnoses were: early - 63 (32,1%) eyes;

intermediate - 43 (21,9%) eyes; advanced

- 90 (45,9%) eyes. Advanced cases was sub-

divided into two categories: non neovascular

(dry) - 12 (6,1%) eyes and neovascular (wet)-

78 (39,8%) eyes. 24 (26,7%) eyes with cicatrix

disciformis complication and 45 (40%) had

FFA alone. 34,9% patients with low vision

and 27,8% with blindness. A higher rate of

neovascular ARMD was noted in Cicendo

Eye Hospital.

Key words: ARMD, neovascular, visual acuity.

CDK. 2009; 36(1) : 28-32

Benzo (

) pyrene (BP) is a carcinogenic com-

pound that is supposed to be able to induce

chromosomal damage. The mutagenic effect

of BP has been studied using MN test on poly-

chromatic erythrocyte (PCE) cells of albino

mice femur bone marrow. Mice were injected

with 0.1 ml of 0.3% (b/v) BP subcutaneously

at the shoulder, every day at the same time

for ten days. After 120 days, treated and non-

treated mice were killed by cervical dislocation.

Their femur bone marrow cells were prepared

on object glass by smear technique followed

by Giemsa»s staining. The appearance of micro-

nucleus (MN) in PCE cells were examined

microscopically by the magnificfication of 2000.

The amount of MN in PCE (MNPCE) were

evaluated in 1000 PCE cells and called MNPCE

frequency. BP treatment could increase MNPCE

frequency up to 38.82 Ø 8.70 (n=10) per 1000

PCE cells compared to MNPCE frequency of

2.19 Ø 0.99 per 1000 PCE cells in control group

(n=10). The significant increase of MNPCE

frequency indicated the relatively high muta-

genic effect of BP.

Key words: benzo (

) pyrene, micronucleus, carcinogenic.

CDK. 2009; 36(1) : 33-36

Mutagenicity Test of

Benzo(

)pyrene

by Microneucleus

Method on Albino Mice

(Mus musculus) Bone

Marrow

Yana Sumpena*, Rochestri Sofyan*,

Rusi Rusilawati**

*Nuclear Technology Research and Development

Center - BATAN, Indonesia

**Universitas Pendidikan Indonesia, Indonesia

Clinical Characteristics

of ARMD Patients at

Cicendo Eye Hospital

Bandung

Erry

Health System and Policy Research

Development Center, Department of Health,

Republic of Indonesia, Jakarta, Indonesia

Epidermal Growth Factor

Receptor (EGFR) Sebagai Sasaran

Terapi Kanker Kolorektal

Santosa*, C. Suharti **

Perserta Program Pendidikan Dokter Spesialis I, ** Kepala Sub Bagian

Hematologi Onkologi Medik Bagian Penyakit Dalam FK UNDIP/RS. Dr. Kariadi Semarang