Cancer is a major human and animal health problem worldwide and is the second leading cause of death in the world wide. Over the past 30 years .significant progress has been achieved in understanding the molecular basis of cancer. The accumulation of this basic knowledge has established that cancer is a variety of distinct disease and that defective gene cause this disease. Further gene defect are diverse in nature and can involve either loss or gain of gene function.

1. Major Credit Seminar
On
Advancements in Cancer
Research with Special
Reference to Pathogenesis
and Diagnosis
Presented
by
Dr. Rahul G.
Kadam
Ph.D Scholar

2. Present Cancer Scenario..
• Out of the total deaths in world 12-13 % deaths are due to
cancer..
• In world 8.2 million people died due to cancer during 2013.
• By 2030 deaths are expected to rise up to 12.0 million.
• The cancer deaths are exceeding the cardiac deaths.
• Every day 2000 peoples died by cancer worldwide.
• Among all these losses
40 % deaths can be avoided
by early diagnosis and according
treatment.

3. “ An abnormal mass of tissue, the growth of which
exceeds and is uncoordinated with that of the normal
tissues and persists in the same excessive manner
even after cessation of the stimuli that evoked the
change.”
New growth composed of cells originally derived
from normal tissues, that have undergone heritable
genetic changes allowing them to become relatively
unresponsive to normal growth controls and to
expand beyond their normal anatomical boundaries.
Cancer

4. TYPES OF NEOPLASM
BENIGN NEOPLASMS
Designated by the suffix – ‘oma’
• Adenoma – glandular epithelium
• Papilloma – epithelial tumor forming finger like projections with a
connective tissue core
MALIGNANT NEOPLASMS
• Sarcoma – from mesenchymal tissue
• Carcinoma – from epithelial tissue

5. CLASSIFICATION/NOMENCLATURE
HISTOGENIC CLASSIFICATION
Based on the origin of neoplastic cell types.:
• Mesenchymal tumours: Arise in cells of embryonic mesoderm
Benign – oma; malignant – sarcoma
• Epithelial tumours:
Glandular – adenoma/adenocarcinoma
Squamous / basal
• Non epithelial: fibrous, cartilage, bone, muscle, etc
Some tumors have more than one parenchymal cell type
– Mixed tumors –derived from a single germ cell layer that differentiates
into more than one cell type.
– Teratomas – made of a variety of parenchymal cell types that derive from
more than one germ cell layer formed by totipotent cells that are able to
form ectoderm, endoderm & mesoderm.

6. Tissue of origin Benign Malignant
A)Tumors of mesenchymal
origin
1.Connective tissue and
derivatives
Fibroma
Lipoma
Chondroma
Osteoma
myxoma
Fibrosarcoma
Liposarcoma
Chondrosarcoma
Osteogenic sarcoma
myxosarcoma
2.Endothelial and related
tissues
Hemangioma
Lymphangioma
Meningioma
-
Hemangiosarcoma
Lymphangiosarcoma
Invasive meningioma
mesothelioma
3.Tumours of Hematopoietic
cells
-
Lymphoma
-
-
Lymphoid leukaemia
Lymphosarcoma
Myeloid leukaemia
Multiple myeloma
4.Tumours of Muscle Leiomyoma
Rhabdomyoma
Leiomyosarcoma
Rhabdomyosarcoma
B)Tumors of Epithelial origin Papilloma
-
Adenoma
melanoma
Transititonal cell papilloma
-
Squamous cell carcinoma
Basal cell carcinoma
Adenocarcinoma
Melano carcinoma
Transitional cell carcinoma
Seminoma
c)Tumours of nervous
tissue
neuroma neuroblastoma
WHO & IARC ,Lyon, 2000

7. DEVELOPMENT
OF
CANCER

8. METALOPROTINEASEMETALOPROTINEASE

10. Development of malignant tumour
Less than 10 mutation required

11. Etiology of cancerEtiology of cancer
Intrinsic factors
• HEREDITY
• AGE
• PIGMENTATION
. SEX
. TUMOUR IMMUNITY
EXTRINSIC FACTOR
•CHEMICALS
•RADIANT ENERGY
•CHRONIC IRRITATION
•HORMONE
•PARASITES
•ONCOGENIC VIRUS
Chronic irritation : Kangari,
Parasite
:Gongylonema.neoplasticum

12. Environmental Carcinogens
• A cancer-causing agent
• Three main types:
– Chemical
– Physical (radiation)
– Biological (especially virus)
• Direct-acting
• Indirect-acting (must be metabolized to activated
metabolic forms
• Direct-acting carcinogens are already electrophilic
• Indirect-acting carcinogens are metabolically activated
into electrophilic species

13. How Cancer Arises
1. Cancer cells violate the civic rules that govern normal
cells by not responding to go-signals for proliferation and
stop-signals for reproduction
2. Cancer cells descend from a common ancestral cell:
clonal origin. But at some point one of the off-springs
mutate that becomes worse with more mutation, and finally
the accumulated mutated cells disobey all civic controls of
normal cells in a tissue, becoming invasive and malign.
3. Since mutations occur at the gene level, that is, DNA
molecules that reside in the nuclei of the cells, most human
cancer be traced there.

14. Molecular Basis of Cancer
• Tumors are monoclonal
proliferation
• Tumors carry genetic
defect that are not lethal
(inherited or acquired)
• Transformed cells
acquire gene defects that
allow them to form tumor

15. What are the genes involved in Cancer?
• A lot of genes!
• Like what?
• Genes promote growth eg. RAS
• Genes inhibit growth eg. P53
• Genes control apoptosis eg.
Bcl-2
• Genes of DNA repair
• And others….
Functional
classification
Up regulated
genes (%)
Down
regulated
genes(%)
Metabolism 21 30
Cell adhesion 4 4
Cell structure 3 6
Immune
response
6 9
Functional classification of genes
discriminating the normal rat
Mammary gland from NMU-induced
tumors
( Marsen M.et al., 2005)
Oncogenes and tumor suppressors

16. Current gene list and technology

17. Knudsen’s “two- hit”
hypothesis
Two separate
mutations, one
in each allele of
a tumor
suppressor
gene, are needed
to cause cancer

18. 18
How cellular oncogenes arise
Cellular oncogenes arise from proto-oncogenes
Proto-oncogenes are not bad genes.
Normal genes for regulation of cell proliferation
and survival
When it change the structure and activity by
mutation: causing cancer
Gain-of-function mutation

19. • Targeted genes:
– 1. Proto-oncogenes (oncogenes)
– 2. Tumor suppressor genes
– 3. Genes controlling apoptosis
– 4. Genes regulating DNA repair
• Other genes involved:
– Genes regulating angiogenesis
– Genes enhancing invasion and metastasis
• Carcinogenesis is a multistep process
– At both genetic and phenotypic levels
– Progression results from accumulation of genetic
defects
The cancer –related gene produce six basic
change.

20. What does a cell need to be “cancer”?
The hallmark of cancer
1. ONCOPROTEIN
2. RB GENE
3. BAX gene
4. TELOMERASE
5. VEGE, bFGC,
THROMBOSPODIN-1
(Sheibani et al.,1999)
6. E-CADHERINS , BETA
CATEINS

21. Most cells are quiescent and are in the G0 (inactive) part of the cell cycle
Most adult cells are NOT actively dividing
Mutation in one of the four genes that regulate cell cycle. RB.CDK4,CyclinD
,CDKN2A

22. G1
S
RB
Adenovirus E1A
HPV E7
SV40 Lg T
APOPTOSIS
p53
Adenovirus E1B(55K)
HPV E6
SV40 Lg TAdenovirus E1B (19K)
(Bcl2-like)
Viral Oncogenes Induce Proliferation
and Suppress Apoptosis
RB protein unable to bind the E2F
DNA viruses can ruin two of the best understood Tumour supressor gene.
P53 gene is a monitor of stress.

23. Molecular basis of cancer

25. Classification of oncogenes
1. Growth factors – c sis,
2. Growth factor receptors
(RTK) - ERBB2, fms
3. Non receptor tyrosine
kinases - abl, src
4. GTP binding - RAS
5. DNA damage repair -
ATM, MSH2, B cl2
6. Serine/ threonine
kinases
7.Nuclear Transcription
Factors – MYC,MYB,JUN,
FOS
8. Misc - cell surface
APC/ DCC
Imogene : Gene mutated such that the protein is produced in
higher quantity or is more active and initiates tumor formation
Imogene : Gene mutated such that the protein is produced in
higher quantity or is more active and initiates tumor formation

26. How Cellular Oncogenes ArisePoint
mutation
.

28. Tumor suppressor: Gene that normally inhibits tumor formation; mutation or poor
expression releases the inhibition

30. MDM2 ,triggers transcription for many gene

31. Key tumor suppressor genes are mutated
Molecular Policeman

32. BRCA1 and BRCA2, two famous genes whose mutations confer a high increased risk of breast
cancer on carriers, are both associated with a large number of DNA repair pathways,
XERODERMA PIGMENTATION

33. Early detection is the key!

34. Cancer diagnosis comprises
of
.involves evaluation of the patient’s history,
 clinical examinations
paraneoplastic disorder
 review of laboratory test results
 radiological data, (X-ray.CT scan ,MRI. Ultrasound
imaging)
 Biopsy
 Cancer staging
Diagnostic approaches of tumor.

35. Stage 0: carcinoma in situ.
Stage I: cancers are localized to one
part of the body
Stage II: cancers are locally advanced.
Stage :Whether a cancer is designated as
Stage II or Stage III can depend on the
specific type of cancer;
Stage IV: cancers have often metastasized, or spread to other organs or
throughout the body.
TNM SYSTEM COMMONLY USED METHOD
OF STAGING BASD ON PRIMARY LESION. .

36. Grade
GX Grade cannot be assessed (Undetermined grade)
G1 Well-differentiated (Low grade)
G2 Moderately differentiated (Intermediate grade)
G3 Poorly differentiated (High grade)
G4 Undifferentiated (High grade)
The American Joint Committee on Cancer recommends the following
guidelines for grading tumors (1):

37. IMAGING
 Malignancy is based on imaging information ,later confirmed on
histology
 Ultrasound (kondyo et al.,2008)
Computed topography,(Drosot et al.,1996)
Magnetic resonance imaging(MRI)(kaiser et al 1992)
Metabolic and functional Imaging
Molecular imaging with magnetic resonance spectroscopy.(MRS)
Position emission topography,(PET)(Grahek D et al 2004)

38. Cytology and Histopathological Technique
1. Still a gold standard for diagnosis of tumour.
Recent technique
 Imaging
IHC
PCR
Flow cytometary
 FISH
MICROARRAY
NANOTECHNOLOGY

39. • What is tumor marker?
 Tumor markers are glycoproteins
produced by tumor cells or by other
body cells in response to cancer or
other conditions.
 As tumor cells multiply, spreads
& tissue is damaged TMs increase
in concentration.
• How it produced?
Tumor Markers
• Where do the TMs found?
 These substances can be found
in the blood (plasma, serum),
urine, saliva, tissue fluid, in the
tumor tissue or in other tissues.

40. Sr.Sr.
No.No.
Disease/TissueDisease/Tissue MarkersMarkers
11 Bladder cancerBladder cancer BTA, NMP22, CEA, CA125, CA19-9BTA, NMP22, CEA, CA125, CA19-9
22 Breast cancerBreast cancer CA15-3, CEA, CA27-29CA15-3, CEA, CA27-29
33 Colorectal cancerColorectal cancer CEA, CA 19-9CEA, CA 19-9
44 GestationalGestational HCGHCG
55 Liver cancerLiver cancer AFPAFP
66 Lung CancerLung Cancer CEA, NSECEA, NSE
77 Melanoma sink cancerMelanoma sink cancer TA-90, S100TA-90, S100
88 Multiple myelomaMultiple myeloma B2MB2M
99 Ovarian CancerOvarian Cancer CA125, CA72-4, HCG, AFPCA125, CA72-4, HCG, AFP
1010 Pancreatic CancerPancreatic Cancer CA 19-9, CEACA 19-9, CEA
1111 Prostate CancerProstate Cancer PSA, PAPPSA, PAP
1212 Gastric CancerGastric Cancer CEACEA
1313 Testicular CancerTesticular Cancer HCG, AFP, PAPHCG, AFP, PAP
List of commonly used TMs

41. • Ag –Ab based Techniques :
i) ELISA
ii) Radio-immunoassay
iii) Flow Cytometry
iv) Immunohistochemistry
• Molecular Genetic Techniques :
i) PCR / RT PCR
ii) Fluorescence in situ Hybridization ((FISH)
iii) Comparative Genomic Hybridization (CGH)
• Other Techniques :
i) Spectophotometry
Tumor Markers detection Methods

42. Immuno-histochemistry has been utilized extensively to
determine estrogen, progesterone and Her-2 neu receptor status
in breast cancer in predicting response to therapy (Diaz, Leslie et
al.,2005)
Detection of over expression of c-erbB2 oncoproteins by ICH in
canine mammary tumour.( Mayilkumar K et al ,.2009)
Immuno- histochemistry(IHC)
IHC based on specific antigenic determinants in the cell of tissue by use
of polyclonal or monoclonal antibodies.(Ramos-Vara et al., 2005)

43. Immunohistochemistry (IHC)
• Ag + [Ab + fluorescent dye]
• Detection of protein of tumors
by using specific antisera &
MCAb directed against them.
• Detection of surface receptors to
intracellular matrix to hormone
can be detected with ease.
• Help ti determine the primary
site of metastatic tumor.
(Ramos-Vara et al., 2005)

44. A single gene chip can even hold representative fragments from the entire human
genome.

45. Different microrray labeling kit

47. • Present in perfectly normal conditions
• Act as chaperones making sure that
the cell’s proteins are in the right shape
and in the right place at the right
time.
• HSPs also help to shuttle proteins
• Transport old proteins to “garbage
disposals” /proteasome inside the cell.
Heat shock Protein

48. • For normal function
of p53 it require
transient interaction
of Hsp 90 and then
degraded
• Mutation of p53
• Mutated p53 have
unstableconformation
• Extended interaction
with Hsp 90 and prevent
their normal degradation
• Accumulation of mutant
p53

49. • Over-expression of HSP70 and HSP90
correlates with a bad prognosis of tumor
• Overexpression of HSP27 in leukemia
osteosarcoma ovarian cancer, prostate
cancer
• Overexpression of HSP70 indicates high
grade malignancy

50. According to the US National Cancer Institute (OTIR, 2006)
“Nanotechnology willchange the very foundations of cancer diagnosis,
treatment, and prevention”
NANOTECHNOLOGY IN CANCER

51. . Nanotechnology will make possible to run test without physically
altering the cells or tissue

52. Cancer nanotechnology is emerging as a new field of interdisciplinary
research, cutting across the disciplines of biology, chemistry,
engineering, and medicine, and is expected to lead to major advances
in cancer detection, diagnosis, and treatment .(Menon U, Jacobs IJ.
2000, Ferrari M. 2005.)
Schematic diagram showing nanotechnology applications in cancer through
molecular tumor imaging, early detection, molecular diagnosis, targeted therapy,
and cancer bioinformatics

53. Nanodevices Are
Small Enough to Enter Cells
Cell
White
blood cell
Water
molecule
Nanodevices
Nanodevices

54. Nanodevices Can Improve Cancer
Detection and Diagnosis
ImagingNanotechnology Physical Exam,
Symptoms

55. Nanodevices Can Improve Sensitivity
and determine
which cells are
cancerous or
precancerous.
Precancerous cells
Normal cells
Nanodevices
could potentially
enter cells
Precancerous cells
Normal cells

56. Nanodevices Can
Preserve Patients’ Samples
Cells from patient
Cells preserved
Active state preserved
Cells altered
Active state lost
Additional tests
Cells from patient
Nanotechnology Tests
Traditional Tests

57. Nanodevices Can Make Cancer Tests
Faster and More Efficient
Patient A Patient B

59. Laser Capture Microdissection

60. Cancer prevention

61. Conclusion
1.Histopathology remains the standard conventional
method.
2. Recent technique such as imaging ,ICH ,PCR ,flow
cytometry ,FISH, CSH ,and microarry nanotechnalogy
contribute a major break through in diagnosis prognosis
of cancer.
3.In future a multimodal imaging approach will evolve,
enhancing diagnostic accuracy thus minimizing loss of
lives due to cancer.

62. Cosmic Energy essential to maintain the order of our life and expand
our consciousness, it is base for our all action and functions and to
lead healthy and happy life. To remove all disorder of body. More
cosmic energy is obtained through MEDITATION.