neoplasia

NEOPLASIA
DEFINISI: NEOPLASIA
PERTUMBUHAN BARU DAN PERTUMBUHAN BARU ADALAH NEOPLASIA
TERMINOLOGI TUMOR
NEOPLASIA JUGA MENYEBABKAN PEMBENGKAKAN, TETAPI PADA WAKTU DAHULU,
NONNEOPLASTIK TUMOR (HAL YANG MENAKUTKAN) SEKARANG NEOPLASIA
ONKOLOGI MEMPELAJARI TUMOR / NEOPLASIA.
KANKER TUMOR GANAS
ONKOLOGI INGGRIS (SIR RUPERT WILLIS) NEOPLASIA
SEMUA NEOPLASIA TERGANTUNG PADA HOST NUTRISI DAN SUPPLY VASKULER,
BEBERAPA AKIBAT PENGARUH HORMONAL.

NOMENKLATUR
TUMOR (JINAK / GANAS) TERDIRI DARI:
L. SEL NEOPLASIA PROLIFERASI SEL PARENKHIM
2. STROMA : JARINGAN PENYOKONG DAN PEMBULUH DARAH
SEL PARENKHIM PROLIFERASI PENTING PADA NEOPLASIA AKAN TETAPI
PERTUMBUHAN DAN EVOLUSI NEOPLASIA TERGANTUNG DARI SROMA.
PADA BEBERAPA TUMOR, STROMA SEDIKIT NEOPLASIA LUNAK DAN MENGKILAT
KADANG SEL PARENKHIM MEN STIMULI PEMBENTUKAN STROMA KOLAGEN
DESMOPLASIA ( SCIRRHOUS MAMMA )
NOMENKLATUR BERDASARKAN KOMPONEN PARENKHIM
TUMOR JINAK + OMA
GANAS

NOMENKLATUR TUMOR
TISSUE OF ORIGIN
I. COMPOSED OF ONE PARENCHYMAL CELL TYPE
A. MESENCHYMAL TUMORS
L. CONNECTIVEVTISSUE& DERIVATIVES

2. ENDOTHELIAL &RELATED TISSUE

BLOOD VESSELS
LYMPH VESSELS
SYNOVIUM
MESOTHELIUM
BRAIN COVERINGS
3. BLOOD CELLS & RELATED CELLS
HEMATOPOIETIC CELLS
LYMPHOID TISSUE
4. MUSCLE
SMOOTH
STRIATED

BENIGN

MALIGNANT

FIBROMA
LIPOMA
CHONDROMA
OSTEOMA

FIBROSARCOMA
LIPOSARCOMA
CHONDROSARCOMA
OSTEOSARCOMA

HEMANGIOMA
LYMPHANGIOMA

ANGIOSARCOMA
LYMPHANGIOSARCOMA
SYNOVIAL SARCOMA
MESOTHELIOMA
INVASIVE MENINGIOMA

MENINGIOMA

LEUKEMIAS
MALIGNANT LYMPHOMA
LEIOMYOMA
RHABDOMYOMA

LEIOMYOSARCOMA
RHABDOMYOSARCOMA

B. EPITHELIAL TUMORS
l. STRATIFIED SQUAMOUS

SQUAMOUS PAPILLOMASQUAMOUS CELL/EPIDERMOID CARCINOMA

2. BASAL CELLS OF SKIN/ADNEXA
BASAL CELL CARCINOMA
3. EPITHELIAL LINING
GLANDS/DUCTS
ADENOMA
ADENOCARCINOMA
PAPILLOMA
PAPILLARY CARCINOMA
CYSTADENOMA
CYSTADENOCARCINOMA
4. RESPIRATORY PASSAGES
BRONCHOGENIC CARCINOMA
BRONCHIAL ADENOMA /
CARCINOID
5. NEUROECTODERM
NEVUS
MALIGNANT MELANOMA
6. RENAL EPITHELIUMRENAL TUBULAR ADENOMA
RENAL CELL CARCINOMA
7. LIVER CELLS
LIVER CELL ADENOMA
HEPATOCELLULAR CARCINOMA
8. URINARY TRACT EPIT
TRANSITIONAL CELL PAPILLOMA
TRANSITIONAL CELL CA
9. PLACENTAL EPITHELIUM
HYDATIDIFORM MOLE
CHORIOCARCINOMA
l0. TESTICULAR EOITHELIUM/GERM CELL
EMBRYONAL CARCINOMA

II. MORE THAN ONE NEOPLASTIC

CELL TYPE-MIXED TUMORS
l. SALIVARY GLANDS
2. BREAST
3. RENAL ANLAGE

PLEOMORPHIC ADENOMA
/MIXED TUMOR OF SAL.ORIGIN
FIBROADENOMA

MALIGNANT MIXED TUMORS

OF SALIVARY GLAND ORIGIN
MALIGNANT CYSTOSARCOMA
PHYLLODES
WILMSTUMOR

III. MORE THAN ONE NEOPLASTIC CELL TYPE

DERIVED FROM MORE THAN ONE GERM
LAYER-TERATOMOUS
l. TOTIPOTENTIAL CELLS IN GONADS/IN
EMBRYONIC RESTS
MATURE TERATOMA/DERMOID CYST IMMATURE TERATOMA/TERATOCA

KARAKTERISTIK NEOPLASMA JINAK DAN GANAS

1. DIFERENSIASI DAN ANAPLASIA
2. RATE OF GROWTH
3. INVASI LOKAL
4. METASTASIS

DIFERENSIASI: TDD WELL

MODERATE
POORLY
UNDIF

LACK OF DIFFANAPLASIA
(MORFOLOGI DAN FUNGSI)
DENGAN TANDA KEGANASAN SEL
TERDAPAT PULA TUMOR GIANT CELL

DISPLASIA
CIS
RATE OF GROWTH TUMOR JINAK BERTAHUN2
GANAS CEPAT TERGANTUNG DERAJAT DIFERENSIASI
INVASI LOKAL JINAK EXPANSIF / KAPSUL
GANAS INFILTRATIF. INVASI, DESTRUKSI JARINGAN SEKITAR

METASTASIS
SECARA: l. SEEDING OF BODY CAVITY AND SURFACE
RONGGA PERITONEUM, PLEURA, PERIKARDIUM,
SUBARACHNOID,
SENDI ( OVARIUM PSEUDOMYXOMA PERITONEI )
2. LIMFATIK
3. HEMATOGEN

COMPARISONS BETWEEN BENIGN AND MALIGNANT TUMORS

CHARACTERISTICS

BENIGN

MALIGNANT

DIFFERENTIATED/ANAPLASIA

WELL DIFF, STRUCTURE MAY BE

TYPICAL OF TISSUE OF ORIGIN

SOME LACK DIFF WITH ANAPLASIA

STRCTURE IS PFTEN ATYPICAL

RATE OF GROWTH

USUALLY PROGRESSIVE AND

SLOW, MAY COME TOA STANDSTILL OR REGRESS. MITOTIC
FIGURES ARE RARE AND NORMAL

ERRATIC AND MAY BE SLOW TO RAPID

MITOTIC FIGURES MAY BE NUMEROUS
AND ABNORMAL

LOCAL INVASION

USUALLY COHESIVE AND EXPANSILE WELL-DEMARCATED MASSES

THAT DO NOT INVADE OR INFILTRATESURROUNDING NORMAL
TISSUES

LOCALLY INVASIE, INFILTRATING THE

SURROUNDING NORMAL TISSUES,
SOMETIMES MAY BE SEEMINGLY COHESIVE ANG EXPANSIVE

METASTASIS

ABSENT

FREQUENTLY PRESENT, THE LARGER

AND MORE UNDIFF THE PRIMARY,
THE MORE LIKELY ARE METASTASES

EPIDEMIOLOGI

OK KANKER ADALAH KELAINAN PERTUMBUHAN SEL DAN BEHAVIOR

PENYEBAB DIBEDAKAN PADA TINGKAT SELULER DAN SUBSELULER.
PENGETAHUAN TENTANG ASAL KANKER
MISAL: SIR PERCIVAL POTT AGENT KIMIA KANKER INSIDENSI MENINGKAT
KANKER SCROTUM EXPOSE KRONIK (PADA PEKERJA CEROBONG ASAP)
STUDI EPIDEMIOLOGI ETIOLOGI BERHUBUNGAN DENGAN TERUTAMA LINGKUNGAN,
RAS (GENETIK?), KULTUR NEOPLASIA GANAS.
JUGA BEBERAPA PENYAKIT MERUPAKAN FAKTOR RISIKO GANAS

INSIDENSI KANKER
USA (1994) 538.000 KEMATIAN (23% DARI SELURUH MORTALITAS)
DATA INI TIDAK TERMASUK KEMATIAN 700.000 (KURABEL, NON-MELANOMA,
DAN 10.000 CIS, >> SERVIKS, PAYU DARA.

CANCER INCIDENCE AND MORTALITY BY SITE AND SEX

PERKIRAAN CANCER INCIDENCE BY SITE AND SEX (1994)
MALE

FEMALE

MELANOMA(SKIN)-3%
MOUTH-3%
LARYNX-1,5%
LUNG-16%
PANCREAS-2%
COLON,RECTUM-12%
URINARY TRACT-9%
PROTATE-32%
LEUKEMIA, LYMPHOID TISSUE-7%
ALL OTHERS-13,5%

MELANOMA (SKIN)-3%
MOUTH-2%
LUNG-13%
BREAST-32%
PANCREAS-2%
COLON, RECTUM-13%
OVARY-4%
UTERUS-8%
URINARY TRACT-4%
LEUKEMIS, LYMPHOID TISSUE-6%
ALL OTHERS-13%

PERKIRAAN CANCER DEATHS BY SITE AND SEX (1994)

MALE

FEMALE

BRAIN-2%
ESOPHAGUS=3%
LUNG-33%
LIVER/BILIARY TRACT-2%
PANCREAS-4%
STOMACH-3%
COLON, RECTUM-10%
URINARY TRACT-5%
PROSTATE-13%
LEUKEMIA, LYMPHOID TISSUE-8%
ALL OTHERS-17%

BRAIN-2%
LUNG-23%
BREAST-18%
LIVER/BILIARY TRACT-2%
PANCREAS-5%
COLON, RECTUM-11%
OVARY-5%
UTERUS-4%
URINARY TRACT-3%
LEUKEMIA, LYMPHOID TISSUE-8%
ALL OTHERS-19%

FAKTOR GEOGRAFI DAN LINGKUNGAN

TERDAPAT PERBEDAAN INSIDENSI DAN MORTALITAS PADA BERBAGAI NEGARA.
MISAL: MORTALITAS CA GASTER (M/F) 7-8X JEPANG DP USA
CA PARU USA 2X DP JEPANG, BELGIA LEBIH TINGGI DARI USA
MELANOMA 6X NEW ZEALAND DR ICELAND
GEOGRAFI <=> LINGKUNGAN
MORTALITAS ORANG2 JEPANG YANG IMIGRASI KE USA DAN ORANG JEPANG YANG
LAHIR DI USA BEDA KARENA PENGARUH LINGKUGAN & KULTUR
(LINGKUNGAN, TEMPAT KERJA, MAKANAN, KEGIATAN ORANG)
UV
ASBESTOS, VINYL CHLORIDE, 2 NAPHTYLAMINE PEKERJAAN
ALKOHOL CA OROFARING, LARING, ESOFAGUS
SIROAIA HCC
SIGARETCA MULUT, FARING, LARING, ESOFAGUS, PANKREAS, BLADDER
ALKOHOL +TOBACCO UPPER AURODIGESTIVE TRACT
CA SERVIKSFIRST INTERCOURSE DAN NUMBER SEX PARTNERS

USIA
HEREDITER
MY MOTHER AND FATHER BOTH DIED OF CANCER. DOES THAT MEAN
I AM DOOMED TO GET IT?
TIDAK HANYA PENGARUH LINGKUNGAN TAPI FAKTOR PREDISPOSISI HEREDITER.
CA PARU CIGARETTE SMOKING +

INHERITED CANCER SYNDROMES (AUTOSOMAL DOMINANT)

INHERITED PREDISPOSITION INDICATED BY STRONG FAMILY HISTORY
OF UNCOMMON CANCER AND/OR ASSOCIATED MARKER PHENOTYPE
FAMILIAL RETINOBLASTOMA
FAMILIAL ADENOMATOUS POLYPS OF THE COLON
MULTIPLE ENDOCRINE NEOPLASIA SYNDROMES
NEUROFIBROMATOSIS TYPES 1 & 2
VON Hippel-Lindau syndrome
FAMILIAL CANCERS
EVIDENST FAMILIAL CLUSTERING OF CANCER BUT ROLE OF INHERITED
PREDISPOSITION MAY NOT BE CLEAR IN AN INDUVIDUAL CASE
BREAST CANCR
OVARIAN CANCER
COLON CANCER OTHER THAN FAMILIAL ADENOMATOUS POLYPOSIS

AUTOSOMAL RECESSIVE SYNDROMES OF DETICTIVE DNA REPAIR

XERODERMA PIGMENTOSUM
ATAXIA-TELENGECTASIA
BLOOM SYNDROME
FANCONI ANEMIA

ACQUIRED PRENEOPLASTIC DISORDERS

REPLIKASI SEL TERMASUK TRANSFORMASI KEGANASAN, REGENERASI, HIPERPLASIA
DAN PROLIFERASI DISPLASIA ORIGIN NEOPLASIA GANAS.
HIPERPLASIA ENDOMETRIUM ADENOKARSINOMA
DISPLASIA SERVIKS KARSINOMA
PEROKOK SIGARETMETAPLASIA, DISPLASIA MUKOSA BRONKHUS CA
BRONKHOGENIK
SIROSIS HEPATIS REGENERASI PARENKHIM AKTIF HCC (80%)
NON-NEOPLASTIS DISOREDERS:
GASTRITIS KRONIK ATROPI-ANEMIA PERNISIOSA
SOLAR KERATOSIS KULIT
KOLITIS ULSERATIFA
LEUKOPLAKIA (R. MULUT, VULVA, PENIS)

KONDISI
PREKANKER

MOST BENIGN NEOPLASMS DO NOT BECOME CANCEROUS

ADENOMA VILOSA KOLON UKURAN BESAR GANAS (50% KASUS)
TGTG DARI DERAJAT RISIKO?

BIOLOGI PERTUMBUHAN TUMOR

TUMOR GANAS 4 FASE: l. PERUBAHAN MALIGNAN PADA SEL TARGET
TRANSFORMASI
2. PERTUMBUHAN SEL TRANSFORMASI
3. INVASI LOKAL
4. METASTASIS JAUH
FAKTOR-FAKTOR: l. KINETIK PERTUMBUHAN SEL TUMOR
2. ANGIOGENESIS TUMOR
3. PROGRESI DAN HETEROGENETAS

KINETIK PERTUMBUHAN SEL

HOW LONG DOES IT TAKE TO PROUCE A CLINICALLY OVERT TUMOR MASS?
ORIGINAL TRANSFORMED CELL(DIAMETER 10UM) 30 POPULATION DOUBLING TO
10(9) SEL (BERAT KIRA2 1 GR) MERUPAKAN MASA YANG PALING KECIL YANG
DAPAT DI DETEKSI SECARA KLINIK. 10(12)1 KG, UKURAN MAXIMUM.
PADA SAAT TUMOR DAPAT DI DETEKSI SIKLUS HIDUP SEL KOMPLIT.
NORMAL CELL
TRANSFORMATION
SINGLE TUMOR CELL
PROGRESSION
30 DOUBLINGS
PROLIFERATION OF GENECALLY UNSTABLE CELLS
1 GR SMALLEST CLINICALLY
DETECTABLE MASS
TUMOR CELL VARIANTS HETEROGENETTY
10 DOUBLINGS

MICROSCOPIC METASTASES

1 KG MAXIMUM MASS
COMPATIBLE WITH LIFE

METASTASES

(cell doubling)

NORMAL CELL
CARCINOGEN INDUCED CELL CHANGE

TUMOR CELL

TUMOR CELL VARIANTS

CLONAL EXPANSION OF
SURVIVING CELL VARIANT

NONANTIGENIC
INVASIVE
METASTATIC
REQUIRING FEWER GROWTH FACTORS

HUMAN SOLID MALIGNANCY

(clonal evolution
generation of tumor cell
heterogeneity)

SIKLUS SEL G0,G1,S,G2 DAN M, TETAPI SEL KANKER HANYA G0 / G1

KEBANYAKAN TIDAK PADA
REPLIKASI POOL
PADA TUMOR YANG TUMBUH CEPAT GROWTH FRACTION KIRA2 20%

-RATE OF TUMOR GROWTH TERGANTUNG DARI GROWTH FRACTION DAN DERAJAT

IMBALAN PRODUKSI DAN CELL LOSS
LEUKEMIA, LIMFOMA, SMALL CELL CA PARU HIGH GROWTH FRACTION
PERJLN PENY CEPAT
CA COLON, MAMMAE LOW GROWTH FRACTION DAN CELL PRODUCTION
EXCEEDS CELL LOSS LAMBAT
-GROWTH FRACTION OF TUMOR CELL SUSEPTABILITAS THDP KHEMOTERAPI
PADA TUMOR2 YANG AGRESIF (LIMFOMA) SENSITIF KHEMOTERAPICURED
-MITOSIS
HOW LONG? A CELL CYCLE TIME 3 HARI DAPAT TAHUN2 DIAGNOSIS
PADA STADIUM LANJUT.
KOLON, PARU SETELAH DIAG. 3 BULAN +

ANGIOGENESIS
PENTING BLOOD SUPPLY --. PERTUMBUHAN TUMOR
FOLKMAN SEL2 TUMOR PADA KULTUR DAPAT TUMBUH PADA VASKULARISAI
HANYA PADA NODUL BERUKURAN DIAMETER 1-2 MM.
BILA NODUL INI IMPLANTASI PADA JARINGAN TERJADI BLOOD SUPPLY DARI
JARINGAN SEKITARNYA. PERTUMBUHAN TUMOR TERGANTUNG DARI
VASKULARISASI.
PADA TUMOR SOLID DAPAT TERJADI NEKROSIS.
ANGIOGENESIS JUGA BERPERAN PADA METASTASIS
PENELITIAN: TERDAPAT KORELASI ANTARAANGIOGENESIS DAN KEMUNGKINAN
METASTASIS (MELANOMA, CA MAMMAE INVASIVE, CA PARU.
TUMOR ASSOCIATED ANGIOGENIC FACTORS DI HASILKAN OLEH SEL TUMOR /
SEL INFLAMASI (MAKROFAG) PADA TUMOR2 INFILTRASI.
AL; FIBROBLAST GROWTH FACTOR
TGF, TGF,EGF,PDGF,VEGR.

TUMOR PROGRESSION AND HETEROGENEITY

DENGAN BERJALANNYA WAKTU TUMOR AGRESIF / POTENSIAL MALIGNITAS
MENINGKAT. ( CA KOLON LESI PRENEOPLASTIK TUMOR BENIGNA CA INVASIF
KEADAAN INI DISEBUT TUMOR PROGRESSION.
INCREASING MALIGNANCY TUMBUH CEPAT, INVASIF, METASTASIS JAUH.
SEL BERBEDA INVASIF, RATE OF GROWTH, KESANGGUPAN METASTASIS,
KARIOTIPE, RESPONS HORMONAL, SUSEPSIBEL THDP OBAT
ANTIKANKER.
TRANSFORMASI SEL AKIBAT SEL TIDAK STABIL MUTASI
P53 TUMOR SUPPRESSOR GENES DAMAGE DNA AKUMULASI SEL MUTASI
TUMOR GANAS MONOKLONAL BY THE TIME KLINIKHETEROGEN (FASE
SEL DOUBLING) (DPT SEBELUM KLINIK)
SUBKLON MUTANT INI VARIABEL.
OSTEOGENIC SARCOMA METATASIS SUBLLON TELAH
TERJADI SAAT PDRT KE DOKTER
TUMOR2 KELENJAR LIUR; SUBKLON AGRESIF LATE, JRG

MEKANISME INVASI DAN METATASIS

INVASI DAN METASTASIS MORBIDITAS DAN MORTILITAS

TERLEPASNYA SEL TUMOR DARI MASSA PRIMER KE DALAM SISTIM PEMBULUH DARAH /
LIMFATIK PERTUMBUHAN SEKUNDER PADA DISTANT SITE MELALUI BEBERAPA
LANGKAH.
PENELITIAN DENGAN TIKUS JUTAAN SEL YANG LEPAS DARI TUMOR PRIMER DAN MASUK
KE SIRKULASI SETIAP HARINYA HANYA MENGHASILKAN BEBERAPA METAS

INVASI OF EXTRACELLULAR MATRIX

VASCULAR DISSEMINATION
HOMING OR TUMOR CELLS

INVASION OF ECM
JARINGAN TDD ECM: MEMBRANA BASALIS
JARINGAN PENYOKONG INTERSTITIAL
KOMPONEN: KOLAGEN, GLIKOPROTEIN DAN
PROTEOGLIKAN

STEP: DETACHMENT OF TUMOR CELL FROM EACH OTHER

ATTACHMENT TO MATRIX COMPONENT
DEGRADATION OF ECM
MIGRATION OF TUMOR CELLS

METASTASIS HEMATOGEN
PRIMARY TUMOR TRANSFORMED CELL
CLONAL EXPANSION, GROWTH,
DIVERSIFICATION

ECM

METASTATIC SUBCLONE

ADHESION TO AND INVASION OF BASEMENT

MEMBRANE

PASSAGE OF ECM

INTRAVASATION
VENULE

INTERACTION WITH HOST LYMPHOID CELLS

TUMOR CELL EMBOLUS
ADHESION TO BASEMENT MEMBRANE
EXTRAVASATION

METASTATIC TUMOR
METASTATIC DEPOSIT

AGENT KARSINOGENIK DAN INTERAKSI SELULER

BANYAK AGENT MENYEBABKAN KERUSAKAN GENETIK DAN INDUKSI SEL
TRANSFORMASI NEOPLASTIK.
l. KARSINOGEN KIMIA
2.RADIASI
3. VIRUS ONKOGEN

KARSINOGENESIS KIMIA
SIR PERCIVAL POTT KARSINOMA KULIT SKROTUM PADA PEKERJA
PEMBERSIH CEROBONG ASAP AKIBAT EXPOSE KRONIK GELAJA
POLISIKLIK AROMATIK HIDROKARBON
AROMATIC AMINE DAN AZO DYES
NATURALLY OCCURING CARCINOGENS: ASPERGILLUS FLAVUS HCC
AFLATOXIN
NITROSAMINES AND AMIDES
MISCELLANEOUS AGENTS: ASBESTOS, CIGARETTE , VINYL CHLORIDE,
INHALASI CHROMIUM, NICKEL

CHEMICAL CARCINOGENESIS

CARCINOGEN
DETOXIFICATION
METABOLIC
ACTIVATION

EXCRETION

ELECTROPHILIC
DETOZIFICATION
INITIATION
BINDING TO DNA DNA REPAIR
ADDUCT FORMATION
CELL DEATH

PERMANENT DNA
LESION: INICIATED CELL
CELL PROLIFERATION:
ALTERED DIFFERENTIATION
PROMOTION
NEOPLASTIC CELL

NORMAL CELL

MAJOR CHEMICAL CARCINOGENS

DIRECT-ACTING CARCINOGENS
ALKYLATING AGENTS: BETA-PROPIOLACTONE
DIMETHYL SULFATE
DIEPOXYBUTANE
ANTICANCER DRUGS (CYCLOPHOSPHAMIDE, CHLORAMBUCIL, NITROSOUREAS)
ACYLATING AGENTS: 1-ACETYL-IMIDAZOLE
DIMETHYLCARBAMYL CHLORIDE
PROCARCINOGENS THAT REQUIRE METABOLIC ACTIVATION
POPYCYCLIC AND HETEROCYCLIC AROMATIC HYDROCARBONS
BENZ(A) ANTHRACENE
BENZO(A,P)PYRENE
DIBENZ(A,H)ANTHRACENE
3-METHYLCHOLANTHRENE
7,12-DIMETHYLBENZ(A)ANTHRACENE
AROMATIC AMINES, AMIDES, AZO DYES
2-NAPHTHYLAMINE(BETA-NAPHTHYLAMINE)
BENZIDINE
2-ACETYLAMINOFLOURENE
DIMETHYLAMINOAZOBENZENE (BUTTER YELLOW)

NATURAL PLANTS AND MICROBIAL PRODUCTS

AFLATOXIN B1
GRISEAFULVIN
CYCASIN
SAFROLE
BETEL NUTS
OTHERS
NITROSAMINE AND AMIDES
VINYL CHLORIDE, NICKEL, CHROMIUM
INSECTICIDES, FUNGICIDES
POLYCHLORINATED BIPHENYLS

RADIASI
SINAR ULTRAVIOLET DARI MATAHARI / IONIZING ELECTROMAGNETICS DAN
PARTIKEL RADIASI DAPAT MENYEBABKAN TRANSFORMASI SEL.
UV CA SEL SKUAMOSA, BASALIOMA, MELANOMA
PEMBENTUKAN PIRIMIDIN DIMERS SEL2 PADA XERODERMA PIGMENTOSUM
(GENETIC HETEROGE DG 7 VARIANT YANG BERBEDA) MUTASI CA KULIT
IONISASI RADIASI , BOM ATOM SETELAH 4 DEKADE KANKER MAMMA
IONISASI RADIASI ATAXIA TELANGIEKTASIA ( PDRT ATAXIA SEREBELUM DAN
TELENGIEKTASIA OKULOKUTANEOUS) KEGANASAN LIMFOID
DISERTAI IMUNODEFESIENSI DAN RENTAN TERHADAP INFEKSI SINOPULMONAR.
(GENETIC HETEROGEN. 6 MOLEKUL VARIANT)
ANEMIA FANCONI PREDISPOSISI LEUKEMIA, ANEMIA ANAPLASTIK PROGRESIF
CONGENITAL MALFORMATION (POST EXPOSURE AGENT GENOTOXIC)
SINDR. BLOOM ( IMUNODEFISIENSI BERAT, GROWTH RETARDATION DAN PREDISPOSISI
PD BBRP KANKER) HIPERSENSITIF THDP AGENT2 YANG MERUSAK DNA (UV DAN
RADIASI) DEFEK DNA REPAIR AUTOSOMAL RECESSIVE

<== DNA DAMAGE

KARSINOGEN VIRUS
*TRANSFORMASI VIRUS DNA HOST CELL GENOM STABIL.
INTEGRATED VIRUS TIDAK SANGGUP MELAKUKAN SIKLUS REPLIKASI KOMPLIT
GANGGUAN PADA SAAT VIRUS INTEGRASI
*GEN VIRUS TRANSCRIBED EARLY ( SIKLUS HIDUP VIRUS) PENTING UNTUK
TRANSFORMASI ( TAMPAK PADA TRANSFORMED CELL)
VIRUS DNA: HPV
EBV
HBV
VIRUS RNA: HUMAN T-CELL LEUKEMIA VIRUS TYPE 1

HOST DEFENSE AGAINST TUMORSTUMOR IMMUNITY

TUMOR ANTIGEN: TUMOR SPECIFIC ANTIGENS (TSaS) TERDAPAT HANYA PADA SEL TUMOR
TUMOR ASSOCIATED ANTIGEN (TAAs) TERDAPAT PADA SEL TUMOR
DAN SEL NORMAL.
ANTITMOR EFFECTOR MECHANISMS:
CYTOTOXIC T LYMPHOCUTES (PROTEKTIF TU PADA KEGANASAN OLEH VIRUS)
NK CELLS
MAKROFAG
HUMORAL AKTIFASI KOMPLEMEN
INDUKSI ANTIBODY-DEPENDENT CELLULAR TOXICITY OLEH
IMMUNOSURVEILENCE (DEF IMUN KANKER)
IMMUNOTHERAPY AND GENETHERAPY TUMORS
ADOPTIVE CELLULAR THERAPY:
IL-2 GENERATES LYMPHOKINE-ACTIVATED KILLER CELLS
TUMOR INFILTRATING LYMPHOCYTES (LEBIH POTEN TRANSFECTED DG GENE
FOR TNF- (POTENT ANTI TUMORCYTOKINE)
CYTOKINE THERAPY:
IL-2, INTERFERON- (IFN-) DAN IFN-, TNF-,
HAEMPOIETIC GROWTH FACTOR, NK CELLS
ANTIBODY-BASED THERAPY:
? MONOCLONAL ANTIBODIES AGAINT CERTAIN B-CELL LYMPHOMA YANG
DIKONYUGASI DG RICIN POTENT TOXIC
HASIL IMMUNOTOXIN
LEUKEMIA DAN LIMFOMA

KLINIK
EFEK TUMOR PADA HOST
1. LOKAI DAN PENGARUH THDP SEKITAR
2. AKTIFITAS FUNGSI (SENTESIS HORMON)
3. PERDARAHAN DAN INFEKSI SEKUNDER (ULSERASI PERMUKAAN)
4. AKUT (RUPTUR & INFARK)
CANCER CACHEXIA
SINDROMA PARANEOPLASTIK

PARANEOPLASTC SYNDROME
CLINICAL SYNDR

ENDOCRINOPATHIES
CUSHINGS SYNDROME

SYNDR OFINAPPROPRIATE
ADH SECRETION
HYPERCALCEMIA

HYPOGLICEMIA
CARCINOID SYNDROME

MAJOR FORMS OF
UNDERLYING CANCER

CAUSAL MECHANISM

SMALL CELL CA OF LUNG

ACTH OR AGTH-LIKE
SUBSTANCE

PANCREATIC CA
NEURAL TUMORS
SMALL CELL CA OF LUNG
INTRACRANIAL NEOPLASM
SQUAMOUS CA OF LUNG

BREAST CA
RENAL CA
ADULT T CELL LEUKEMIA/LIMFOMA
OVARIAN CA
FIBROSARCOMA
OTHER MESENCHYMAL SARCOMAS
BRONCHIAL ADENOMA (CARCINOID)
PANCREATIC CA
GASTRIC CA

ADH OR ATRIAL NATRIURETIC HORMONE

PARATHYR.HORMONE
RELATED PEPTIDE TGF
TNF, IL-1

INSULIN/INSULIN LIKE
SEROTONIN, GRADYKININ
HISTAMINE

POLYCYTHEMIA
RENAL CA
CEREBELLAR HEMANGIOMA
HCC

ERYTHROPOIETIN

NERVE & MUSCLE SYNDR

MYASTHENIA
BRONCHOGENIC CA
DISORDERS OF SSP & SST

?IMMUNOLOGIC, TOXIC
BREAST CA

DERMATOLOGIC DISORDERS
ACATHOI\SIS MIGRANS
GASTRIC CA
?IMMUNOLOGIC,
LUNG CA ?SECRETION OF EIPDERUTERINE CA
MA GF
DERMATOMYOSITIS
BRONCHOGENIC, BREAST CA
OSSEOUS, ARTICULAR & SOFT TISSUE CHANGES
HYPERTROPHIC OSTEOBRONCHOKENIC CA
ARTHROPATHY & CLUBBING OF
THE FINGERS

?IMMUNOLOGIC, ?TOXIC

UNKNOWN

VASCULAR & HEMATOLOGIC CHANGES

VENOUS THROMBUS
PANCREATIC CA
TUMOR PRODUCTS
(TRAUSSEAUSS PHENOMENON)
BRONCHOGENIC CA (MUCINS) THT ACTIVATE
OTHERS CANVER
CLOTTING
NONBACTERIAL THROMBOTIC
ADVANCED CANCER HYPERCOAGULABILITY
ENDOCARDITIS
ANEMIA
THYMIC NEOPLASM
UNKNOWN
OTHERS
NS

VARIOUS CANCER

TUMOR ANTIGENS, IMMUNE

COMPLEXES

GRADING DAN STAGING

LABORATORY DIAGNOSIS OF CANCER

HISTOLOGIC AND CYTOLOGIC
DATA KLINIK DIAGNOSIS OPTIMAL PATOLOGIST
EVALUASI LAB SPICEMEN (ADEKUAT, REPRESENTATIF)
SPICEMENT EKSISI / BIOPSI
NEEDLE ASPIRATION
CYTOLOGIC SMEAR
IMMUNOHISTOCHEMISTRY
MOLECULAR DIAGNOSIS
FLOW CYTOMETRY IDENTIFIKASI CELL SURFACE ANTIGEN; KLAS LEUKEMIA/LIMFOMA
SPECIMEN: FRESH VC BIOPSY, EFUSI PLEURA/PERITONEAL,
IRIGASI V.U
TDPT HUB. ANTARA CONTENT DNA ABNORMAL DENGAN PROGNOSIS ANEUPLOIDY
PROG BURUK PADA STADIUM DINI CA MAMMA, V.U, KOLOREKTAL, PROSTAT.
FUMOR MARKER

TERAPI
OPERASI
RADIASI
KHEMOTERAPI
HORMONAL