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CANCER
DR ROHINI C SANE
PROFESSOR
DEPARTMENT OF BIOCHEMISTRY
DR D Y PATIL MEDICAL COLLEGE
EBENE
CANCER
• CANCER DISEASE- IN WHICH CELL GROW ABNORMALLY –MALIGNANT NEOPLASM
• (NEW GROWTH )-NEOPLASIA
• A MASS OF TISSUE --...
PROPERTIES OF CANCER CELLS
• UNRESTRAINED GROWTH
• INVANSION OF LOCAL TISSUE
• METASTASIS
MORPHOLOGICAL CHANGES
SHAPE ---R...
BIOCHEMICAL CHANGES
ALTERED GENE REGULATION
INCREASED DNA SYNTHESIS
INCREASED RNA SYNTHESIS
 INCREASED PROTEIN SYNTHES...
BIOCHEMICAL CHANGES
• CARCINOMAS –CANCER ARISES FROM EPITHELIAL TISSUE
• SARCOMAS –MESENCHYMAL TISSUE
• LEUKAEMIAS-WBC
• L...
ETIOLOGY
FAMILIAL GENETIC FACTOR
GEOGRAPHIC FACTORS
• ASIANS-NASOPHARYNGEAL
• JAPNESE –BREAST
• AFRICA –SKIN
• EUROPEANS--...
ENVIROMENTAL FACOTRS
• CIGARETTE SMOKING
• ALCOHOL ABUSE
• TOBACCO
• BETEL NUT
• ARSENIC
• VINYL CHLORIDE
• ASBESTOS
• BEN...
PHYSICAL CARCINOGENS
• RADIENT ENERGY ---UV LIGHT ,IONIZING RADIATIONS
• EXAMPLS –SUNLIGHT ,WELDERS ARC ,UV LAMPS ---SKIN ...
HORMONAL CARCINOGENESIS
• HORMONE SENSITIVE TISSUE ---BREAST ,ENDOMETRIUM,
MYOMETRIUM,VAGINA THYROID, ,LIVER ,PROSTRATE,TE...
Biological carcinogens
• Viruses, parasites ,bacteria
DNA VIRUS
• PAPOVIRUS ---HPV (HUMAN PAPILLOMA VIRUS),SV40B,POLYOMA
V...
RNA VIRUS
ACUTE TRANSFORMING VIRUS :ROUS SARCOMA VIRUS :LEUKEMIA
VIRUS
SLOW TRANSFORMING :MOUSE MAMMARY TUMOR VIRUS
HUMAN ...
CARCINOGENESIS &CHEMICAL CARCINOGENS
INITIATORS
DIRECT –DO NOT REQUIRE METABOLIC ACTIVATION
EXAMPLES ---ALKYLATING AGENTS—...
CARCINOGENESIS & CHEMICAL CARCINOGENS
INDIRECT –
AROMATIC HYDROCARBONS---BENZOPYRENES
TOBACO
COAL
TAR
SMOKE
AROMATIC AMINE...
PROMOTERS OF CARCINOGENS
• NOT CARCINOGENS BUT INITIATE CARCINOGENESIS
• EXAMPLES –PHENOLS,ESTROGENS,ARTIFICIAL SWEETNER
S...
Pro-carcinogens
Proximate carcinogens
Ultimate carcinogens
(free radicals)
Mechanism of action of chemical carcinogens
DIRECT REACTING CARCINOGEN (WITH NO METABOLIC ACTIVATION
)&INDIRECT (WITH META...
Apoptosis
• Dropping /falling of the normal programmed destruction of cells
.,during embryogenesis, development of adult l...
Proto-oncogenes –normal genes –stimulate cell division
Proto-oncogenes (activated by physical, chemical, biological carcin...
Oncogene expression
proto –oncogenes control normal growth &cell division
Mutated versions of proto-oncogenes act as oncog...
Mechanisms of activation of proto-oncogenes to oncogenes
• Promoter and enhancer insertion
• Chromosomal translocation
• G...
ONCOGENES CHROMOSOMES VIRUS ONCOGENE PRODUCTS
abl 9 Abbleson leukemia in
mouse
Tyrosine kinase
erb B 7 Erythroblastosis in...
ONCOSUPPRESSOR ABBREVATIONS CHROMOSOMES
RETINOBLASTOMA RB 13
FAMILLIAL BREAST
CANCER
BRCA1
BRCA2
17
GENE FOR PROTEIN 53 P5...
Retinoblastoma gene RB gene
• Nucleo phosphoprotein –regulates DNA SYNTHESIS
• SWITCH OF CELL PROLIFERATION—SUPPRESS TUMOR...
MODE OF DNA VIRAL ONCOGENESIS
VIRUS + DNA
ALTERATION IN GENE EXPRESSION
CELL TRANSFORMATION
TYPE OF PROTEIN ALTERED
INACTI...
MODE OF RNA VIRAL ONCOGENESIS
RNA
DNA (SINGLE STANDED )
C DNA (DOUBLE STRANDED)
C DNA GETS INCORPORATED IN HOST DNA ---PRO...
IMMUNOLOGIC SURVEILLANCE
• IMMUNE SYSTEM
• RECOGNIZES SPECIFIC ANTIGENS
• DESTROY CANCER CELLS CARRYING ANTIGENS ---STOP A...
Tumor markers
• DEFINITION –BIOLOGICAL SUBSTANCES SYNTHESIZED OR RELEASED
BY CANCER CELLS AND FOUND IN INCREASED AMOUNT IN...
APPLICATIONS OF TUMOR MARKERS
• DIAGNOSIS (SCREENING )
• DIFFENTIAL DIAGNOSIS
• STAGING OF CANCER
• DETECTION OF RECURRENC...
Tumor markers
ENZYMES
PROSTATIC ACID PHOSPHATASE---PROSTRATE CANCER
ALKALINE PHOSPHATASE --- BONE SECONDARIES
PROTEINS
• P...
Tumor markers
HORMONES & THEIR METABOLITE
• Beta HCG ---CHORION
CARCINOMA
• CALCITONIN ---
MEDULARYCARCINOMA
• VANILLYL MA...
CANCER & DIET
• INCREASED ANIMAL FAT
• INCREASED BACTERIAL FLORA
• CONVERSION OF ACIDS & STEROLS
• CARCINOGENS
• BENEFIAL ...
Cancer therapy
• Chronic myeloid leukaemia (CML)
• ONCOGENES C—abl (9 ) ,bcr (22)---protein kinase ,tyrosine kinase
• Trnl...
MONCLONAL
ANTIBODIES
TARGET USED AGAINST CANCER
Ritutab CD20 ON B CELLS BETA CELL LEUKEMIA
HERCEPTIN HER 2/EGFR 2 BREAST C...
IMAGES FROM GOOGLE
Cancer biochemistry
Cancer biochemistry
Cancer biochemistry
Cancer biochemistry
Cancer biochemistry
Cancer biochemistry
Cancer biochemistry
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Cancer biochemistry

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A comprehensive presentation on cancer biochemistry including biochemical changes,carcinogens,mechanism of chemical carcinogenesis ,oncogenes & activation,monoclonal antibodies for cancer therapy,diet ,prevention &tumor markers

Publié dans : Santé & Médecine
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Cancer biochemistry

  1. 1. CANCER DR ROHINI C SANE PROFESSOR DEPARTMENT OF BIOCHEMISTRY DR D Y PATIL MEDICAL COLLEGE EBENE
  2. 2. CANCER • CANCER DISEASE- IN WHICH CELL GROW ABNORMALLY –MALIGNANT NEOPLASM • (NEW GROWTH )-NEOPLASIA • A MASS OF TISSUE ---ABNORMAL ,EXCESSIVE,UNCORDINATED ,PURPOSELESS PROLIFERATION • ONCOLOGY = ONCOS ( TUMOR ) + LOGY (STUDY ) • BENIGN TUMOR---THAT DOSE NOT INVADE /SPREAD –NON CANCEREROUS • MALIGNANT TUMOR /CANCER –INVADES DESTROY TISSUE IN WHICH ORIGINATES –CAN SPREAD IN OTHER TISSUES VIA BLOOD STREAM & LYMPHATIC SYSTEM
  3. 3. PROPERTIES OF CANCER CELLS • UNRESTRAINED GROWTH • INVANSION OF LOCAL TISSUE • METASTASIS MORPHOLOGICAL CHANGES SHAPE ---ROUNDER MOTILITY ---LOSS OF CONTACT INHIBITION OF MOVEMENTS GROWTH --- LOSS OF CONTACT INHIBITION –MULTILAYER /NUMBER OF NUCLEI BIOCHEMICAL CHANGES ALTERED GENE REGULATION ---DNA SYNTHESIS ---RNA SYNTHESIS ---PROTEIN SYNTHESIS---ANABOLISM---GROWTH
  4. 4. BIOCHEMICAL CHANGES ALTERED GENE REGULATION INCREASED DNA SYNTHESIS INCREASED RNA SYNTHESIS  INCREASED PROTEIN SYNTHESIS ANABOLISM---GROWTH FACTORS &HORMONES INCREASED AEROBIC & ANAEROBIC GLYCOLYSIS SYNTHESIS OF LACTIC ACID & LACTIC ACIDOSIS ALTERATION OF CELL SURFACE DUE CHANGES IN COMPOSITION OF GLYCOPROTEINS & GLYCOSPHINGOLIPIDS DECREASED
  5. 5. BIOCHEMICAL CHANGES • CARCINOMAS –CANCER ARISES FROM EPITHELIAL TISSUE • SARCOMAS –MESENCHYMAL TISSUE • LEUKAEMIAS-WBC • LYMPHOMAS • HEPATOMAS –HEPATOCYTES
  6. 6. ETIOLOGY FAMILIAL GENETIC FACTOR GEOGRAPHIC FACTORS • ASIANS-NASOPHARYNGEAL • JAPNESE –BREAST • AFRICA –SKIN • EUROPEANS--COLON • ENVRIMENTAL FACTORS • AGE->50YRS • SEX- MEN >WOMEN
  7. 7. ENVIROMENTAL FACOTRS • CIGARETTE SMOKING • ALCOHOL ABUSE • TOBACCO • BETEL NUT • ARSENIC • VINYL CHLORIDE • ASBESTOS • BENZENE • NAPHTHYLOMINE
  8. 8. PHYSICAL CARCINOGENS • RADIENT ENERGY ---UV LIGHT ,IONIZING RADIATIONS • EXAMPLS –SUNLIGHT ,WELDERS ARC ,UV LAMPS ---SKIN CANCER • FORMATION OF PYRIMIDINE DIMER IN DNA STRAND • FORMATION OF APURINIC OR APYRIMIDINE SITE ELIMINATION OF BASES • BREAKING OF CROSS LINKING OF SINGLE OR DOUBLE STRAND OF DNA IONIZING RADIATIONS –X RAYS ,ALPHA ,BETA ,GAMMA RAYS ,RADIOACTIVE ISOTOPES ,PROTONS ,NEUTRONS • IONIZING RADIATIONS---DAMAGE DNA ,DISLODGE IONS FROM H2O& BIOMOLECULES ,INTERACT WITH PROTEINS, DNA-----CANCER (MUTAGENESIS)
  9. 9. HORMONAL CARCINOGENESIS • HORMONE SENSITIVE TISSUE ---BREAST ,ENDOMETRIUM, MYOMETRIUM,VAGINA THYROID, ,LIVER ,PROSTRATE,TESTIES • ESTROGENS---OVARIAN,ENDOMETRIUM CARCINOMA • CONTRACEPTIVE HORMONES ---BREAST CANCER • ANABOLIC STEROIDS---ATHLETS,LIVER CANCER
  10. 10. Biological carcinogens • Viruses, parasites ,bacteria DNA VIRUS • PAPOVIRUS ---HPV (HUMAN PAPILLOMA VIRUS),SV40B,POLYOMA VIRUS • HERPES VIRUS –EPSTEIN BAR VIRUS • ADENOVIRUS –12,18,31 • HEPITITIS B VIRUS (HBV)
  11. 11. RNA VIRUS ACUTE TRANSFORMING VIRUS :ROUS SARCOMA VIRUS :LEUKEMIA VIRUS SLOW TRANSFORMING :MOUSE MAMMARY TUMOR VIRUS HUMAN T CELL LYMPHOTROPIC VIRUS --- HTLV -1,HTLV II RNA REVERSE TRANSCRIPATASE RNA –DNA NEOPLASIA NOT ALL RETROVIRUSES ARE CARCINOGENIC
  12. 12. CARCINOGENESIS &CHEMICAL CARCINOGENS INITIATORS DIRECT –DO NOT REQUIRE METABOLIC ACTIVATION EXAMPLES ---ALKYLATING AGENTS—CYCLOPHOSPAHMIDE ACYLATING AGENTS-- NITROSOUREA
  13. 13. CARCINOGENESIS & CHEMICAL CARCINOGENS INDIRECT – AROMATIC HYDROCARBONS---BENZOPYRENES TOBACO COAL TAR SMOKE AROMATIC AMINES AZO DYES BETA NAPHTHYL AMINE ACETALAMINO FLUORENE NATURALLY OCCURING ALF TOXIN BETEL NUT MISCELLENEOUS ----- VINYL CHLORIDE ,ASBESTOS ,NI, CARBON MONOXIDE
  14. 14. PROMOTERS OF CARCINOGENS • NOT CARCINOGENS BUT INITIATE CARCINOGENESIS • EXAMPLES –PHENOLS,ESTROGENS,ARTIFICIAL SWEETNER SACCHARINE,CYCLAMATES • METABOLIC ACTIVATION
  15. 15. Pro-carcinogens Proximate carcinogens Ultimate carcinogens (free radicals)
  16. 16. Mechanism of action of chemical carcinogens DIRECT REACTING CARCINOGEN (WITH NO METABOLIC ACTIVATION )&INDIRECT (WITH METABOLIC ACTIVATION FORMS REACTIVE ELECTROPHILES Electrophiles (free radicals)—deficient in electrons Interact with DNA Neutrophiles (chiefly DNA,RNA,PROTEINS) DAMAGE (DNA MUTATION ,DNA repair enzymes fail) Neoplastic transformation Development of cancer
  17. 17. Apoptosis • Dropping /falling of the normal programmed destruction of cells .,during embryogenesis, development of adult life. • Destruction of apoptosis promote inappropriate cell division ,cell survival ---development of cancer
  18. 18. Proto-oncogenes –normal genes –stimulate cell division Proto-oncogenes (activated by physical, chemical, biological carcinogens )----- oncogenes ---growth factor ,growth factor receptors ,signal transduction proteins Tumor suppressor gene –inhibit cell division Normal cell –balanced activity of tumor suppressor & protooncogene activator genes ---normal growth & repair Neoplasia –uncontrol cell division ---(1)decreased suppressor activity (2)increased proto-oncogene activity
  19. 19. Oncogene expression proto –oncogenes control normal growth &cell division Mutated versions of proto-oncogenes act as oncogenes examples • Growth factors • Growth factor receptors • Protein involved in signal transduction(protein kinase that phosphorylates tyrosine /serine residue )---GTP binding protein • Proteins involved in signaling gene expression in nucleus • some growth factor induce growth but not cell division –cell grows large in size without ever dividing • 50 types of growth factors identified –first platelet diving growth factor (PDGF)
  20. 20. Mechanisms of activation of proto-oncogenes to oncogenes • Promoter and enhancer insertion • Chromosomal translocation • Gene amplification • Point mutation • Effect of oncogene on growth ---putting one foot on accelerator of automobile • Tumor suppressor gene ---taking one foot from the break
  21. 21. ONCOGENES CHROMOSOMES VIRUS ONCOGENE PRODUCTS abl 9 Abbleson leukemia in mouse Tyrosine kinase erb B 7 Erythroblastosis in chicken Receptor for E & PR erb –A 17 Erythroblastosis in chicken Transforming growth factor receptors myc 08 Myelocytoma in chicken Platelet derived growth factor ras 12 Rat sarcoma GTPase
  22. 22. ONCOSUPPRESSOR ABBREVATIONS CHROMOSOMES RETINOBLASTOMA RB 13 FAMILLIAL BREAST CANCER BRCA1 BRCA2 17 GENE FOR PROTEIN 53 P53 17
  23. 23. Retinoblastoma gene RB gene • Nucleo phosphoprotein –regulates DNA SYNTHESIS • SWITCH OF CELL PROLIFERATION—SUPPRESS TUMOR FORMATION
  24. 24. MODE OF DNA VIRAL ONCOGENESIS VIRUS + DNA ALTERATION IN GENE EXPRESSION CELL TRANSFORMATION TYPE OF PROTEIN ALTERED INACTIVATION OF TUMOR SUPPRESSOR NEOPLASM
  25. 25. MODE OF RNA VIRAL ONCOGENESIS RNA DNA (SINGLE STANDED ) C DNA (DOUBLE STRANDED) C DNA GETS INCORPORATED IN HOST DNA ---PROTEINS /ENZYMES , HORMONES SYNTHESIZED NEOPLASTIC CHANGES
  26. 26. IMMUNOLOGIC SURVEILLANCE • IMMUNE SYSTEM • RECOGNIZES SPECIFIC ANTIGENS • DESTROY CANCER CELLS CARRYING ANTIGENS ---STOP ABNORMAL GROWTH • IF IMMUNOLOGIC SURVELLIENCE FAILS CANCER GROWS
  27. 27. Tumor markers • DEFINITION –BIOLOGICAL SUBSTANCES SYNTHESIZED OR RELEASED BY CANCER CELLS AND FOUND IN INCREASED AMOUNT IN BLOOD ,BODY FLUID OR TISSUES INDICATING PRESENCE OF CANCER
  28. 28. APPLICATIONS OF TUMOR MARKERS • DIAGNOSIS (SCREENING ) • DIFFENTIAL DIAGNOSIS • STAGING OF CANCER • DETECTION OF RECURRENCE • MONITORING RESPOSE TO THERAPY (PROGNOSIS)
  29. 29. Tumor markers ENZYMES PROSTATIC ACID PHOSPHATASE---PROSTRATE CANCER ALKALINE PHOSPHATASE --- BONE SECONDARIES PROTEINS • PROSTRATE SPECIFIC ANTIGEN----PSA--PROSTRATE CANCER • MULTIPLE MYELOMA----SERUM PROTEIN IMMUNOGLOBULIN/BENCE JONES PROTEINS • C PEPTIDE ---INSULINOMA • BETA MICROGLOBULINS –BETA CELL LYMPHOMAS CARBOHYDRATE • CARBOHYDRATE ANTIGEN (CA—125)—OVARIAN ,ENDOMETRIUM • CARBOHYDRATE ANTIGEN (CA—549)—BREAST ,OVARIAN
  30. 30. Tumor markers HORMONES & THEIR METABOLITE • Beta HCG ---CHORION CARCINOMA • CALCITONIN --- MEDULARYCARCINOMA • VANILLYL MANDELLIC ACID – NEUROBLASTOMA • PROLACTIN –PITUITARY ADENOMA • PTH –RENAL,BREAST,LIVER ONCOFETAL ANTIGENS • ALPHA FETO PROTEINS ---(AFP) HEPATOMA • CARCINOEMBRYONIC ANTIGEN--- (CEA)--COLON ,LUNG ,GIT
  31. 31. CANCER & DIET • INCREASED ANIMAL FAT • INCREASED BACTERIAL FLORA • CONVERSION OF ACIDS & STEROLS • CARCINOGENS • BENEFIAL ROLE OF VITAMIN C ,E ,SELENIUM ,BETA CAROTENE • TRACE ELEMENTS ---Manganese ,zinc ,selenium, copper • Tomatto ,cabbage ,cauliflower
  32. 32. Cancer therapy • Chronic myeloid leukaemia (CML) • ONCOGENES C—abl (9 ) ,bcr (22)---protein kinase ,tyrosine kinase • Trnlocation of bcr gene to abl gene --bcr –abl gene –protein kinase enzyme • Bcl---abl not regulated • Increased protein kinase • Gleevec ---antitumor drug ---STI 571 USED IN TREATMENT OF BCR- ABL GENE—(tyrosine KINASE) ---90% cancer patients respond to treatment –rapid growth decreased but side effects
  33. 33. MONCLONAL ANTIBODIES TARGET USED AGAINST CANCER Ritutab CD20 ON B CELLS BETA CELL LEUKEMIA HERCEPTIN HER 2/EGFR 2 BREAST CANCER BERACIZUMAB VGEF COLORECTAL CANCER NILITINIB TYROSINE KINASE SOLID CANCER IMATINIB TYROSINE KINASE NON SMALL CELL LUNG CANCER GENTFITINIB TYROSINE KINASE CML PANITUMUMAB EGFR COLORECTAL CANCER
  34. 34. IMAGES FROM GOOGLE

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