CANCER

2.  Characterized by uncontrolled cellular growth
& development, leading to excessive
proliferation & spread of cells.
 Cancer is the second largest killer disease.
 Cancer originated from the character of
cancerous cells which migrate & adhere and
cause pain to any part of the body.
 Uncontrolled growth of cells result in tumors.

3.  Benign tumors:
 They usually grow by expansion & remain
encapsulated in a layer of connective tissue.
 These are not life-threatening. Eg. Moles.
 Malignant tumors or cancers:
 Characterized by uncontrolled proliferation
& spread of cells to varies parts of the body,
a process referred to as metastasis.
 These are life-threatening. Eg. Lung cancer.

4.  Cancers arising from epithelial cells are
referred to as carcinomas, while that from
connective tissue are known as sarcomas.

5.  General & morphological changes:
 Shape of cells:
 Rounder in shape
 Alterations in cell structures:
 The cytoskeletal structure of the tumor cells
with regard to actin filament is different.

6.  Loss of contact inhibition:
 The normal cells are characterized by contact
inhibition, i.e. they form monolayers.
 They cannot move away from each other.
 The cancer cells form multilayers due to loss
of contact inhibition.
 Cancer cells freely move & get deposited in
any part of the body, a property referred to
as metastasis.

8.  Loss of anchorage dependence:
 The cancer cells can grow without
attachment to the surface.
 But normal cells which firmly adhere to the
surface.
 Tumor cells have altered permeability &
transport.

9.  Increased replication and transcription:
 Synthesis of DNA & RNA is increased.
 Increased glycolysis:
 Elevation in aerobic & anaerobic glycolysis
due to increased energy demands of
multiplying cells.
 Reduced requirement of growth factors:
 Require less quantities of growth factors.

10.  Synthesis of fetal proteins:
 During fetal life, certain genes are active,
leading to the synthesis of specific proteins.
 These genes are suppressed in adult cells.
 Alterations in the structure of molecules:
 Changes in the structure of glycoproteins &
glycolipids.

11.  Include physical, chemical, genetic &
environmental factors.
 Chemical carcinogens:
 Almost 80% of human cancers are caused by
chemical carcinogens in nature.
 The chemicals may be organic
(dimethylbenzanthracene) or inorganic
(arsenic, cadmium) in nature.

12.  Occupation e.g. asbestos, benzene.
 Diet: e.g aflatoxin B produced by fungus
(Aspergillus flavus) contamination of
foodstuffs, particularly peanuts.
 Drugs certain therapeutic drugs can be
carcinogenic e.g. diethylstibesterol.
 Life style e.g. cigarette smoking.

13.  Few of the chemicals are directly
carcinogenic.
 Majority of them require prior metabolism to
become carcinogenic.
 The enzymes cytochrome P450 responsible for
the metabolism of xenobiotics.

14.  The carcinogens can covalently bind to
purins, pyrimidines & phosphodiester bonds
of DNA, causing unrepairable damage.
 The chemical carcinogens frequently cause
mutations which may finally lead to the
development of cancer, hence they are
regarded as mutagens.

15.  A laboratory test to check the carcinogenecity
of chemicals.
 Use of a special mutant strain of bacterium,
Salmonella typhimurium (His-).
 This organism cannot synthesize histidine.
 Histidine should be supplied in the medium
for its growth.

16.  Addition of chemical carcinogens causes
mutations (reverse mutation) restoring the
ability of bacteria to synthesize histidine (His+).
 By detecting the strain of Salmonella (His+) in
the colonies of agar plates, the chemical
mutagens can be identified.
 It can detect about 90% of chemical carcinogens.
 This is a preliminary screening procedure.

17.  Radiation energy:
 Ultraviolet rays, x-rays and y-rays have
been proved to be mutagenic in nature
causing cancers.
 These rays damage DNA.

18.  Carcinogenic viruses:
 Oncogenic viruses may be either DNA viruses
or RNA viruses.
Class Members
DNA viruses
Adenovirus Adenovirus 12 & 18
Herpesvirus Epstein-Barr virus, herpes simplex virus
Papovirus Papilloma virus, polyoma virus
RNA viruses
Retrovirus type B Mammary tumor virus of mouse
Retrovirus type C Leukemia, sarcoma

19.  Cancer is caused by a genetic change in a
single cell.
 Two types of regulatory genes – oncogenes &
antioncogenes.
 Oncogenes:
 The genes capable of causing cancer are
known as oncogenes.
 These are discovered in tumor causing viruses.

20.  Viral oncogenes are similar to certain genes
present in the normal host cells referred as
protooncogenes.
 About 40 viral & cellular proto-oncogenes.
 Proto-oncogenes encode for growth regulating
proteins.
 The activation of protooncogenes to
oncogenes is an important step in the
causation of cancer.

21.  Viral insertion into chromosome:
 Certain retroviruses (genetic material RNA)
infect cells, a complementary DNA (cDNA) is
made from their RNA by the enzyme reverse
transcriptase.
 This cDNA inserted into the host genome.
 The integrated double-stranded cDNA is
referred as provirus.

22.  This proviral DNA takes over the control of
the transcription of cellular chromosomal
DNA and transforms the cells.
 This ultimately causes cancer (E.g. avian
leukemia).
 Chromosomal translocation:
 Some tumors exhibits chromosomal
abnormalities.

23.  This due to rearrangement of genetic
material (DNA) by chromosomal
translocation i.e. splitting off a small
fragment of chromosome which is joined to
another chromosome.
 It usually results in over expression of proto-
oncogenes.

24.  Burkitt’s lymphoma, a cancer of B-
lymphocytes.
 Gene amplification:
 Several fold amplifications of certain DNA
sequences are observed in some cancers.
 Administration of anticancer drugs
methotrexate (inhibitor of dihydrofolate
reductase) is associated with gene
amplification.

25.  The drug becomes inactive due to gene
amplification resulting in a several fold
increase in the activity of dihydrofolate
reductase.
 Point mutations:
 The replacement of one base pair by another
results in point mutation.

26.  Growth factors:
 Cell proliferation is stimulated by growth factors.
 Growth factor binds to protein receptor on the
plasma membrane.
 This binding activates cytoplasmic protein kinases
leading to the phosphorylation of intracellular
target proteins.
 The phosphorylated proteins act as intracellular
messengers to stimulate cell division.

27.  Transforming growth factor (TGF-α) is a
protein synthesized & required for the
growth of epithelial cells.
 TGF - α is produced in high concentration in
individuals suffering from psoriasis, a
disease characterized by excessive
proliferation of epidermal cells.

28.  Some oncogenes encoding growth factor
receptors.
 Overexpression and/or structural
alterations in growth factor receptors are
associated with carcinogenesis.

29.  These are a group of signal transducing
proteins.
 Guanosine triphosphate (GTP) – binding
proteins are found in 30% of human cancers.
 Mutation of ras protooncogene is the single-
most dominant cause of many human tumors.

30.  A special category of genes – cancer
suppressor genes or antioncogenes.
 The products of these genes apply breaks &
regulate cell proliferation.
 The loss of these suppressor genes removes
the growth control of cells & a key factor in
the development of several tumors. E.g.
retinoblastoma, carcinoma of lung.

31.  Tumor markers are defined as bio chemical
substance (e.g. hormone, enzyme or
proteins) synthesized & released by cancer
cells or produced by the host in response to
cancerous substance.
 Site:
 In blood circulation, body fluids, cell
membranes, cell cytoplasm.

32. Tumor marker Associated cancer
Oncofetal antigens
Carcinoembryonic antigen (CEA)
Cancer of colon, stomach, lung,
pancreas & breast
Alpha fetoprotein (AFP) Cancer of liver & germ cells of testis
Cancer antigen 125 (CA-125) Ovarian cancer
Hormones
Human chorionic gonadotropin
(hCG)
Choriocarcinoma
Calcitonin Carcinoma of medullary thyroid
Catecholamines & their
metabolites
Neuroblastoma

33. Tumor marker Associated cancer
Enzymes
Prostatic acid phosphatase Prostate cancer
Neuron specific enolase Neuroblastoma
Specific proteins
Prostate specific antigen (PSA) Prostate cancer
Immunoglobulins Multiple myeloma

34.  Carcinoembryonic antigen(CEA):
 CEA is a glycoprotein.
 Present in both carcinoma & embryonic tissue.
 Normal range: <5.0 ng/ml.
 Site: GI mucos, lungs & pancreas
 CEA is a most useful marker in colorectal
cancer.
 Also elevated in breast cancer, pancreatic
gastric & lung cancers.

36.  Human chorionic gonadotropin (β-HCG):
 It is a placental hormone.
 Synthesized by syncytiotrophoblastic cells of
placental villi.
 Normal range: 120,000mIU/mL.
 It is a glycoprotein
 It is a dimer, contain α-subunit & β-subunit.
 Useful tumor marker for gestational tumors &
germ cell tumors of testis & ovary.

38.  Alpha-Fetoprotein(AFP):
 AFP is synthesized in liver, yolk sac & GIT in
fetal life.
 It is a glycoprotein.
 Normal range: <15 ng/ml.
 Chemically related to albumin.
 AFP is the most specific tumor marker for
primary carcinoma of liver.

40.  CA 125:
 It is a tumor marker for ovarian carcinoma.
 Also elevated in breast carcinoma & colorectal
cancers.
 Narmal range: <35 U/ml.
 CA 15-3:
 It is useful tumor marker in breast carcinoma.
 It is more sensitive marker than CEA.
 Normal range: <30 U/ml.

41.  CA 19-9:
 It is useful tumor marker in pancreatic cancer.
 It is also elevated in colorectal
cancer(20%),hepatomas(20 to 50%)and gastric
cancer.
 Normal range: <37 U/ml.

43.  These are identified in breast cancer.
 MCA (Mucin-like carcinoma associated
antigen)
 It is a mucin glycoprotein.
 MAM6:
 It is a epithelial membrane antigen.
 Present on ductal & alveolar epithelial cells.

44.  MSA (mammary serum antigen):
 It is marker of intraductal breast cancer.
 More sensitive marker then CA 15-3.
 MAP (Mitogen activated protein) kinase:
 It is a new breast cancer marker.
 MAP kinase levels are 5 to 20 times higher in
breast cancer as compared to normal breast
tissue.

46.  Prostatic acid phosphatase (PAP):
 It is a tumor marker for prostate cancer.
 Normal range: <2.5ng/ml.
 Prostate specific antigen (PSA):
 It is an organ specific.
 Localized to prostatic ductal cells.
 Normal range: 4.5 µg/L

47.  Neuron –specific Enolase (NSE):
 It is a specific tumor marker of neuro-
endocrine origin.
 It is useful marker in neuroblastomas & lung
cancer.
 NSE:
 Also elevated in small-cell carcinoma of lung
 The upper reference limit: 12.5 µg/L

49.  Textbook of Biochemistry – U Satyanarayana
 Textbook of Biochemistry – DM Vasudevan
 Textbook of Biochemistry – MN Chatterjea