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

BENIGN

MALIGNANT

FIBROMA LIPOMA CHONDROMA OSTEOMA HEMANGIOMA LYMPHANGIOMA

FIBROSARCOMA LIPOSARCOMA CHONDROSARCOMA OSTEOSARCOMA ANGIOSARCOMA LYMPHANGIOSARCOMA SYNOVIAL SARCOMA MESOTHELIOMA INVASIVE MENINGIOMA LEUKEMIAS MALIGNANT LYMPHOMA

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

MENINGIOMA

LEIOMYOMA RHABDOMYOMA

LEIOMYOSARCOMA RHABDOMYOSARCOMA

B. EPITHELIAL TUMORS l. STRATIFIED SQUAMOUS

SQUAMOUS PAPILLOMA

2. BASAL CELLS OF SKIN/ADNEXA 3. EPITHELIAL LINING GLANDS/DUCTS ADENOMA PAPILLOMA CYSTADENOMA 4. RESPIRATORY PASSAGES

SQUAMOUS CELL/EPIDERMOID CARCINOMA BASAL CELL CARCINOMA

ADENOCARCINOMA PAPILLARY CARCINOMA CYSTADENOCARCINOMA BRONCHOGENIC CARCINOMA BRONCHIAL ADENOMA / CARCINOID MALIGNANT MELANOMA RENAL CELL CARCINOMA HEPATOCELLULAR CARCINOMA TRANSITIONAL CELL CA CHORIOCARCINOMA EMBRYONAL CARCINOMA

5. NEUROECTODERM NEVUS 6. RENAL EPITHELIUM RENAL TUBULAR ADENOMA 7. LIVER CELLS LIVER CELL ADENOMA 8. URINARY TRACT EPIT TRANSITIONAL CELL PAPILLOMA 9. PLACENTAL EPITHELIUM HYDATIDIFORM MOLE l0. TESTICULAR EOITHELIUM/GERM CELL 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

DISPLASIA CIS

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

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

DIFFERENTIATED/ANAPLASIA

BENIGN
WELL DIFF, STRUCTURE MAY BE TYPICAL OF TISSUE OF ORIGIN

MALIGNANT
SOME LACK DIFF WITH ANAPLASIA STRCTURE IS PFTEN ATYPICAL

RATE OF GROWTH

USUALLY PROGRESSIVE AND ERRATIC AND MAY BE SLOW TO RAPID SLOW, MAY COME TOA STANDMITOTIC FIGURES MAY BE NUMEROUS STILL OR REGRESS. MITOTIC AND ABNORMAL FIGURES ARE RARE AND NORMAL USUALLY COHESIVE AND EXPANSILE WELL-DEMARCATED MASSES THAT DO NOT INVADE OR INFILTRATESURROUNDING NORMAL TISSUES ABSENT LOCALLY INVASIE, INFILTRATING THE SURROUNDING NORMAL TISSUES, SOMETIMES MAY BE SEEMINGLY COHESIVE ANG EXPANSIVE

LOCAL INVASION

METASTASIS

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 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% FEMALE 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 ELECTROPHILIC DETOZIFICATION INITIATION BINDING TO DNA ADDUCT FORMATION DNA REPAIR NORMAL CELL CELL DEATH EXCRETION

PERMANENT DNA LESION: INICIATED CELL CELL PROLIFERATION: ALTERED DIFFERENTIATION PROMOTION NEOPLASTIC 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 MAJOR FORMS OF UNDERLYING CANCER CAUSAL MECHANISM

ENDOCRINOPATHIES CUSHINGS SYNDROME

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

ACTH OR AGTH-LIKE SUBSTANCE

SYNDR OFINAPPROPRIATE ADH SECRETION HYPERCALCEMIA

ADH OR ATRIAL NATRIURETIC HORMONE PARATHYR.HORMONE RELATED PEPTIDE TGF TNF, IL-1

HYPOGLICEMIA
CARCINOID SYNDROME

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

INSULIN/INSULIN LIKE
SEROTONIN, GRADYKININ HISTAMINE

POLYCYTHEMIA

RENAL CA CEREBELLAR HEMANGIOMA HCC

ERYTHROPOIETIN

NERVE & MUSCLE SYNDR MYASTHENIA DISORDERS OF SSP & SST

BRONCHOGENIC CA BREAST CA

?IMMUNOLOGIC, TOXIC

DERMATOLOGIC DISORDERS ACATHOI\SIS MIGRANS

DERMATOMYOSITIS

GASTRIC CA LUNG CA UTERINE CA BRONCHOGENIC, BREAST CA

?IMMUNOLOGIC, ?SECRETION OF EIPDERMA GF ?IMMUNOLOGIC, ?TOXIC

OSSEOUS, ARTICULAR & SOFT TISSUE CHANGES HYPERTROPHIC OSTEOBRONCHOKENIC CA ARTHROPATHY & CLUBBING OF THE FINGERS VASCULAR & HEMATOLOGIC CHANGES VENOUS THROMBUS PANCREATIC CA (TRAUSSEAUSS PHENOMENON) BRONCHOGENIC CA OTHERS CANVER NONBACTERIAL THROMBOTIC ADVANCED CANCER ENDOCARDITIS ANEMIA THYMIC NEOPLASM OTHERS NS

UNKNOWN

TUMOR PRODUCTS (MUCINS) THT ACTIVATE CLOTTING HYPERCOAGULABILITY UNKNOWN

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