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
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Cancer biochemistry
1. CANCER
DR ROHINI C SANE
PROFESSOR
DEPARTMENT OF BIOCHEMISTRY
DR D Y PATIL MEDICAL COLLEGE
EBENE
2. CANCER
⢠CANCER DISEASE- IN WHICH CELL GROW ABNORMALLY âMALIGNANT 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 âNON CANCEREROUS
⢠MALIGNANT TUMOR /CANCER âINVADES DESTROY TISSUE IN WHICH ORIGINATES
âCAN SPREAD IN OTHER TISSUES VIA BLOOD STREAM & LYMPHATIC SYSTEM
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 âMULTILAYER /NUMBER OF NUCLEI
BIOCHEMICAL CHANGES
ALTERED GENE REGULATION ---DNA SYNTHESIS ---RNA SYNTHESIS ---PROTEIN
SYNTHESIS---ANABOLISM---GROWTH
4. BIOCHEMICAL CHANGES
ďśALTERED GENE REGULATION
ďśINCREASED DNA SYNTHESIS
ďśINCREASED RNA SYNTHESIS
ďś INCREASED PROTEIN SYNTHESIS
ďśANABOLISM---GROWTH FACTORS &HORMONES
ďśINCREASED AEROBIC & ANAEROBIC GLYCOLYSIS
ďśSYNTHESIS OF LACTIC ACID & LACTIC ACIDOSIS
ďśALTERATION OF CELL SURFACE DUE CHANGES IN COMPOSITION OF
GLYCOPROTEINS & GLYCOSPHINGOLIPIDS
ďśDECREASED
8. PHYSICAL CARCINOGENS
⢠RADIENT ENERGY ---UV LIGHT ,IONIZING RADIATIONS
⢠EXAMPLS âSUNLIGHT ,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 âX RAYS ,ALPHA ,BETA ,GAMMA RAYS ,RADIOACTIVE
ISOTOPES ,PROTONS ,NEUTRONS
⢠IONIZING RADIATIONS---DAMAGE DNA ,DISLODGE IONS FROM H2O&
BIOMOLECULES ,INTERACT WITH PROTEINS, DNA-----CANCER
(MUTAGENESIS)
16. Mechanism of action of chemical carcinogens
DIRECT REACTING CARCINOGEN (WITH NO METABOLIC ACTIVATION
)&INDIRECT (WITH METABOLIC ACTIVATION FORMS REACTIVE
ELECTROPHILES
Electrophiles (free radicals)âdeficient in electrons
Interact with DNA Neutrophiles (chiefly DNA,RNA,PROTEINS)
DAMAGE (DNA MUTATION ,DNA repair enzymes fail)
Neoplastic transformation
Development of cancer
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
20. Oncogene expression
proto âoncogenes 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 âcell grows large in size
without ever dividing
⢠50 types of growth factors identified âfirst platelet diving growth factor (PDGF)
21. 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
22. ONCOGENES CHROMOSOMES VIRUS ONCOGENE PRODUCTS
abl 9 Abbleson leukemia in
mouse
Tyrosine kinase
erb B 7 Erythroblastosis in chicken Receptor for E & PR
erb âA 17 Erythroblastosis in chicken Transforming growth factor
receptors
myc 08 Myelocytoma in chicken Platelet derived growth factor
ras 12 Rat sarcoma GTPase
26. Retinoblastoma gene RB gene
⢠Nucleo phosphoprotein âregulates DNA SYNTHESIS
⢠SWITCH OF CELL PROLIFERATIONâSUPPRESS TUMOR FORMATION
27.
28. MODE OF DNA VIRAL ONCOGENESIS
VIRUS + DNA
ALTERATION IN GENE EXPRESSION
CELL TRANSFORMATION
TYPE OF PROTEIN ALTERED
INACTIVATION OF TUMOR SUPPRESSOR
NEOPLASM
29. 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
30. IMMUNOLOGIC SURVEILLANCE
⢠IMMUNE SYSTEM
⢠RECOGNIZES SPECIFIC ANTIGENS
⢠DESTROY CANCER CELLS CARRYING ANTIGENS ---STOP ABNORMAL
GROWTH
⢠IF IMMUNOLOGIC SURVELLIENCE FAILS CANCER GROWS
31.
32. Tumor markers
⢠DEFINITION âBIOLOGICAL SUBSTANCES SYNTHESIZED OR RELEASED
BY CANCER CELLS AND FOUND IN INCREASED AMOUNT IN BLOOD
,BODY FLUID OR TISSUES INDICATING PRESENCE OF CANCER
33. APPLICATIONS OF TUMOR MARKERS
⢠DIAGNOSIS (SCREENING )
⢠DIFFENTIAL DIAGNOSIS
⢠STAGING OF CANCER
⢠DETECTION OF RECURRENCE
⢠MONITORING RESPOSE TO THERAPY (PROGNOSIS)
34. 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 âBETA CELL LYMPHOMAS
CARBOHYDRATE
⢠CARBOHYDRATE ANTIGEN (CAâ125)âOVARIAN ,ENDOMETRIUM
⢠CARBOHYDRATE ANTIGEN (CAâ549)âBREAST ,OVARIAN
36. 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
37. Cancer therapy
⢠Chronic myeloid leukaemia (CML)
⢠ONCOGENES Câabl (9 ) ,bcr (22)---protein kinase ,tyrosine kinase
⢠Trnlocation of bcr gene to abl gene --ď bcr âabl gene âprotein kinase
enzyme
⢠Bcl---abl not regulated
⢠Increased protein kinase
⢠Gleevec ---antitumor drug ---STI 571 USED IN TREATMENT OF BCR-
ABL GENEâ(tyrosine KINASE) ---90% cancer patients respond to
treatment ârapid growth decreased but side effects
38. 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