1. 1

2. Cancer cells are characterized by
three properties
 Unrestrained control of growth
 Immortal
 Invasion of local tissues
 Metastasis
Biomedical importance
 second most common cause for
death world wide
 Humans of all the ages affected and
wide variety of organs are affected
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3.  Radiant energy- UV rays, X- rays, and γ-rays
■ Pyrimidine dimers
■ DNA cross linking
■ Free radical generation
 Chemical agents-
80% of the cancer is caused by the chemicals
Exposure can occur during
 occupation
 Diet
 Life style – cigarette smoking, tobacco ,alcohol
 Other ways ( therapeutic drugs may be
carcinogenic)
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4. class compound
Polycyclic aromatic hydrocarbon Benzopyrene, dimethyl
benzanthracene
Aromatic amines Acetyl aminofluorene, amino
benzene
Nitrosamines Dimethyl and diethyl
nitrosamines
Drugs cyclophosphamide
Naturally occurring compounds Aflatoxin B1, dactinomycin
Inorganic compounds Arsenic, asbestose, beryllium,
cadmium,
chromium
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5.  procarcinogen→ proximate
carcinogen→ ultimate carcinogen
 Bind covalently to macromolecules
including DNA, RNA and proteins
 Carcinogens are electrophiles (
deficient in electrons) readily attack
nucleophilic groups of DNA
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6.  Mutagenesity – can be diagnosed by
Ames test- Salmonella typhimurium( his–ve )
Chemical carcinogen
Salmonella typhimurium( his+ve )
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7.  Oncogenic viruses contain either DNA or RNA
as their genome.
 Integration of viral genes in to the host DNA-
overrules the regulatory checks and balances
of the cellular mechanism- transformation
Virus Abbreviation Associated cancer
Epstein barr virus EBV Burkitt’s lymphoma
Nasopharyngeal
carcinoma
Human papilloma virus HpV Uterine, cervical ca
Hepatitis B virus HBV hepatoma
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8.  Oncogenes are the genes capable causing
cancer
 Michel bishop and harold varmus-
demonstrated oncogene in Rous sarcoma
virus
 The same sequences are also present in
humans- cellular oncogenes designated by
prefix ‘c’ and viral oncogene as ‘v’ eg, c- src
and v- src.
 These are also called as protooncogenes.
 > 100 protooncogenes are present in
humans
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9.  Products of many oncogenes are
polypeptide growth factors e.g. sis gene
produces PDGF
 Act as receptors for growth factors e.g.
erb-B produces receptor for EGF.
 Some act on key intracellular pathways
e.g. src product tyrosine kinase enzyme
phosphorylates tyr residue-activation of
intracellular events.
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10. oncogene Chromoso Virus carrying Oncogene Subcellular
me no. the gene product localization of
oncogene product
abl 9 Abelson leukemia Tyrosine Plasma membrane
virus in mouse kinase
Erb-B 7 Erythroblastosis Receptor for membrane
virus in chicken EGF
Erb-A 17 do Receptor for nucleus
TGF
myc 8 Myelocytoma DNA binding nucleus
virus in chicken protein
sis 22 Simian sarcoma PDGF membrane
virus in monkeys
src 20 Rous sarcoma Tyrosine membrane
virus in chicken kinase
ras 12 Rat sarcoma virus GTPase cytoplasm
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11. Five mechanisms has been described
Promoter insertion
Enhancer insertion
Chromosomal translocation
Gene amplification
Point mutation
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12.  Insertionof viral c DNA near the oncogene
acts as a promoter
PROVIRUS
A. B. LTR LTR
myc myc
………… ………….
Myc mRNA
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13.  Insertion
of viral c DNA down stream of the
oncogene.
PROVIRUS
A. B. myc
LTR LTR
myc
………… …………
Myc mRNA
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14. Reciprocal translocation in Burkitt’s lymphoma
Translocation is from short arm of
chromosome 8 to short arm of chromosome
14 and in reverse process translocation
occures from short arm of chrom. 14 to
chrom. 8
Translocated piece from chrom. 8 contains myc gene
which is placed next to gene transcribing H chain
of immunoglobulin and itself become activated
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15.  Amplification of genes causing increased
expression in to many folds.
 Amplification of certain genes are found in
some tumours.
 Can be induced by
certain anticancer
drugs which causes
drug resistance
 Eg, treatment with
methotrexate
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16.  Point mutation is observed in some cancer
c-ras c-ras
P 21(MUTATION AT 12TH POSITION)
P 21
GTP ase activity Loss of GTPase activity
Diminishes the activity Overstimulation of adenyl cyclase
Of adenyl cyclase
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17.  Growth factors are polypeptide substances
secreted from different cells which causes
mitosis.
 Growth factors may be
Endocrine
Paracrine
Autocrine
Growth factors acts on mitosis via
transmembrane signal transduction
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18. Growth factors Source Function
EGF Mouse salivary Stimulates growth of many epidermal and
gland epithelial cells
Erythropoietin Kidney, urine Development of early erythropoietic cells
IGF-1 and IGF-2 Serum So4 incorporation into cartilage,
mitogenic for chondrocytes and exert
insulin like effects on many cells
Transforming Tumor cells, Similar to EGF
growth factor-a placenta
TGF-b Placenta, Inhibition of fibroblasts
platelets
Platelet platelets Accelerated wound healing
derived growth
factor
Nerve growth Submaxillary Growth of sensory neurons
factor gland
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19. Growth factors Source Function
Granulocyte Endothelial cells and Stimulates
macrophage colony T-cells granulocytes,
stimulating factor monocytes,
megakaryocytes
Granulocyte colony Endothelial cells and Stimulates
stimulating factor fibroblasts granulocytes
Monocyte colony Endothelial cells Stimulates monocytes
stimulating factor
Tumour necrosis monocyte Necrosis of tumour
factor- alpha(TNF-α ) cells, proliferation of
leukocytes
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20.  The products of several oncogene
act as growth factors or receptors
for growth factors
 v-sis codes 100 a.a acids for B chain
of PDGF
 v-erb codes for truncated receptor
for EGF which causes continuous
activation.
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21.  Genes which prevents the causation of
cancer
 These sometimes called as recessive
oncogenes or anti oncogenes
Oncogenes Tumour suppressor genes
Mutation in one of the allele is Mutation in both the alleles is
sufficient required
Gain of function of a protein that Loss of function of a protein
signals cell division
Mutation in somatic cells which is not Mutation in germ cells which is
inherited Inherited
Some tissue preference Strong tissue preference
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22. Oncosupressor gene Abbreviation Chromosome no.
Retinoblastoma RB 13
Wilm’s tumour WT 11
Familial adenomatous FAP 5
polyposis
Deleted in colon cancer DCC 18
Gene for protein-53 p53 17
Familial breast cancer BRAC 3
Von hippel lindau gene VHL 3
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23. Cytokinesis:
The Cell Cycle division of
Mitosis: cytoplasm
division of
M-phase Daughter
cells
the nucleus
G2-phase Cells divide G1-phase
Prep.
for division: Cell growth +
organelles normal cell
duplicate activities
Synthesis of DNA
(chromosomes replicate)
Interphase = S-phase
G1, S, G2
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24. RB 1 GENE
IMPORTANT PROPERTIES
 Gene is located on chrom. 13q14
 Familial retinoblastoma occurs after
identical mutations in both the alleles
 Product of RB( pRB) gene is a
phosphoprotein
 p RB binds certain viral proteins and
forms inactive complexes
 pRB binds to certain transription factors
that are active in S phase thus slowing
cell cycle
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25. Properties of p53 gene
 Gene is located on the chrom. No 17
 Product is a nuclear phosphoprotein
 It binds to specific DNA sequences
 It acts as a transcriptional regulator
 It binds to various viral proteins
forming inactive oligomeric
complexes
 Mutations in p53 gene are the most
common genetic alteration in cancer
and are frequent in colon, breast
and lung cancer
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26. These are the substances released by
the cancer cells and detectable in
blood
useful for the following purposes
 Diagnosis of cancer
 Follow up of cancer and to monitor
effectiveness of therapy.
 Prognosis
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27. common tumor markers
Name Increased in
Alfa fetoprotein Hepatoma, germ cell tumors
Carcinoembryonic antigen Colorectal, gastrointestinal and lung
cancer
Beta HCG choriocarcinoma
Prostate specific antigen Prostrate cancer
calcitonin Medullary carcinoma of thyroid
CA-125 Overian cancer
Alkaline phosphatase Bone secondaries
Neuronal specific enolase Nervous system cancer
Venyl mandelic acid pheochromacytoma
Hydroxy indole acetic acid Carcinoid syndrome
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28.  Chemical nature : is a oncofetal protein
 Sources: in embryonic life mainly produced
by liver and yolk sac
 Normal serum levels: <10µg/L
 Clinical use:
 Diagnosis: of hepatocellular cancer and
germ cell tumor (testicular carcinoma).
 Prognosis: if AFP > 10µg/L and bilirubin >
2mg/dl indicates bad prognosis.
 Monitoring of therapy
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29.  Chemical nature: it is a glycoprotein
 Sources: present in fetal gastrointestinal
tract
 Clinical use:
A. Diagnosis of adenocarcinoma of colon
and levels are increased in smokers and
aged people
B. Main use is monitoring of the colon
cancer
C. CEA may also be raised in 10-15% of
breast cancer
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30.  Chemical nature: it is a extracellular
protease
 Source : prostate gland
 Normal serum levels: it is usually present in
serum either in free form or complex with
anti protease ( alpha-2 macroglobulin).
Normal serum level- 0 to 0.4 µg/L in 40 – 70
years of age
 Clinical use:
 PSA along with the digital examination is
used for screening the prostate cancer in 50-
75 years of age group
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31.  Chemical nature: is a glycoprotein
 Source: trophoblastic tissues of placenta
and testes
 Normal serum levels : < 5 IU/L
 Clinical use:
 markedly elevated in choriocardcinoma
and germ cell tumors
 Mainly used as diagnostic, therapeutic
and prognostic tool for germ cell
tumors
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32.  Chemical nature: polypeptide containing
32 a.a
 Source: secreted from parafollicular cells
of thyroid in response to hypercalcemia
 Normal serum level: 8.8 ng/L
 Clinical uses:
 very useful for screening and diagnosis of
medullary carcinoma of thyroid gland
 Also used to assess severity and
monitoring the therapy
 It is also increased in breast, liver and
lung cancers
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