1. By Dr. El Hassan Mokhamer
Cancer By
Dr. El Hassan Mokhamer

2. What is cancer? Abnormal cell growth (neoplasia)‏
Malignant as opposed to benign
Benign:-
slow growth, non-invasive, no metastasis
Malignant:-
rapid growth, invasive, potential for metastasis

3. BENIGN MALIGNANT NON-INVASIVE INVASIVE / METASTATIC
well-defined borders
irregular borders
well differentiated
poorly differentiated
regular nuclei
irregular, larger nuclei
rare mitoses
more frequent and/ or abnormal mitoses

6. The Vocabulary
Hyperplasia : increased number of cells
Hypertrophy : increased size of cells
Dysplasia : disorderly proliferation
Neoplasia : abnormal new growth
Anaplasia : lack of differentiation
Tumor : originally meant any swelling, but now equated with neoplasia
Metastasis : growth at a distant site

7. Is cancer a heritable disease?
There are heritable cancer syndromes
The majority of cancers, however, are not familial
Cancer is a genetic disease, but the majority of mutations that lead to cancer are somatic

8. A factor which brings about a mutation is called a mutagen.
A mutagen is mutagenic.
Any agent that causes cancer is called a carcinogen and is described as carcinogenic.
So some mutagens are carcinogenic.

9. DNA of a normal cell
This piece of DNA is an exact copy of the DNA from which it came. When the parent cell divided to create two cells, the cell's DNA also divided, creating two identical copies of the original DNA.

10. 2. Mutation of DNA
Here is the same section of DNA but from another cell. If you can imagine that DNA is a twisted ladder, then each rung of the ladder is a pair of joined molecules, or a base pair. With this section of DNA, one of the base pairs is different from the original. This DNA has suffered a mutation, either through mis-copying (when its parent cell divided), or through the damaging effects of exposure to radiation or a chemical carcinogen.

11. Carcinogenesis Theories
I . NATURE and NURTURE THEORY
GENES and ENVIRONMENTAL INTERACTIONS.
Phenotype = Genotype x Environment
• Example: Xeroderma pigmentosum (XP)
II. MULTI-STAGE , MULTI-MECHANISM THEORY .
“Initiation, Promotion, Progression” Theory of Carcinogenesis.
1. “initiation”:- is the Irreversible Alteration of a Cancer-Related Gene.

12. is the Clonal Expansion of the Initiated Cell.
2. Promotion :-
is the Clonal Expansion of the Initiated Cell.
1. Stimulation of Growth of Initiated cells by
Mitogenic growth factors, hormones or
compensatory hyperplasia caused by necrosis or cell removal ( Surgery).
2. Prevention of cell Death ( Apoptosis).
3. Promotion is an Interruptible or Reversible
phase

13. 3. Progression phase:-
1. Stable Alteration of Genes in an Initiated Cell.
2. Either Mutations or Epigenetic Events may Confer the Malignant
Phenotypes of Invasiveness and Metastasis.
III. Mutation/Epigenetic theory
Mutagens:-
1. Physical Agents ( X Rays; UV Light).
2. Electrophilic Chemicals
( Nitrosamines, Benzo (a)pyrenes)

14. Epigenesis:- Alteration of Gene Expression at the Transcriptional,
Translational, or Posttranslational Levels.
1. Translational Level- Altered Methylation of DNA or
Acetylation of Nuclear Proteins.
2. Translational Level- Alternative Splicing of mRNA.
3. Posttranslational Level: Modification of Proteins by
Phosphorylation or Nitrosylation.

15. Epigenetic Carcinogens or Tumor Promoters:-
1. Non-Mutagenic chemicals( e.g., DDT, Phenobarbital).
2. They Act as Either Mitogens and / or Inhibitors of Apoptosis.

16. IV.ONCOGENE/ TUMOR SUPPRESSOR GENE THEORY
1. ONCOGENES
Derived from normal “proto-oncogenes”in all cells
Tumor-specificity (i.e., neu or ERB2 expressed in breast cancer)
- Can be “activated” by amplification of the normal proto-oncogene; mutated to become activated; abnormally expressed.

17. BIOLOGICAL FUNCTIONS OF ONCOGENES
1. Growth Factors/Hormones (e.g., SIS;PDGF)
2. Growth Factor/Hormone-Receptors (e.g.,Neu; EGF-R)
3. Signal Transduction Enzymes (e.g., Ras;G-protein)
4. Transcription Factors (e.g., MYC)

18. TUMOR SUPPRESSOR GENE Must be “de-activated”
• Can be tumor specific (BRCA-1/BRCA-2 in breast tumors; Rb in retinoblastoma,osteosarcoma)
• Can be ubiquitous (p53 in at least 50% of all tumors)

19. Apoptosis
A morphological description of a programmed sequence of events leading to single cell death within a population.
Apoptosis
• during normal development
• in response to environmental insult
• a mechanism to eliminate pre-cancer cells.
The function of apoptosis is to clear
tissues of unwanted cells

20. Necrosis
Apoptosis
Cell swelling
Cell Shrinkage
Loss of membrane
integrity
Membrane integrity remains intact
No energy required
Energy requiring
Groups of cells
Single cells

21. BIOLOGICAL FUNCTIONS OF TUMOR SUPPRESSOR GENES
1. Growth Inhibitors (e.g., TGF-β; glucocortocoids)
2. Growth Inhibitor Receptors
3. Signal Transduction Protein Inhibitors
4. Transcription Factors of Growth Inhibitors

22. Characteristics of Cancer Cells.
1. “Immortal”.
2. Loss of Growth control or “contact inhibition”.
3. Unable to Terminally Differentiate or Apoptose.
4. Have Invasive and Metatastic properties.
5. Have Angiogenic Support System.

23. Mutagens Viruses: insertional mutagenesis Chemicals: DNA adducts
UV and ionizing radiation: single and double strand DNA breaks

24. Characteristics of Cancer Cells
1. Lack differentiation.
2. Fail to undergo apoptosis.
3. Immortal (Do not die).
4. Pile on top of one another to form a tumor.
5. Keep on dividing.
6. Have a well-developed capillary network (Angiogenesis).
7. Able to move to another location (metastasis).

25. Histological Classification of Cancer
Carcinomas :Cancers of epithelial cells(glands, breast, skin, liver,
lung, prostate, intestine & thyroid)
Sarcomas: Cancers of muscle and connective tissues (including bone tissue).
Leukemias : Cancers of blood
Lymphomas: Cancers of lymphatic tissues

26. What causes cancer?

27. Risk Factor
A risk factor is anything that increases a person's chance of getting a disease.
Some risk factors can be changed, and others cannot.
Different cancers have different risk factors

28. Risk Factors a) Inheritance:
BRCA-1 is a gene associated with breast cancer. It is a tumor .suppressor gene
b) Environmental carcinogens:
1. physical; Ionizing Radiation (U.V.,X-rays).
2. chemicals: in tobacco smoke, pollutants like asbestos, pesticides.
3. Viruses:
a) Hepatitis B and C viruses (liver cancer).
b) Epstein-Barr virus (Burkitt lymphoma)
c) Human papilloma virus (cervical cancer).

30. Risk Factor/ Cancer Type
Lung Cancer
Tobacco smoke
Radon
Asbestos and other substances
Air pollution
Breast
Radiation
Genetic changes (Inherited mutation)
Colorectal
Cancer polyp
Genetic alteration
Diet
Cigarette smoking
Ulcerative colitis or chon's disease
Prostate
Certain prostate changes
Race Africans Americans

31. Hepatitis viruses (HCV.HBV) Pancreas Smoking Diabetes Being male
Cancer Type
Risk Factor
Liver
Hepatitis viruses (HCV.HBV)
Pancreas
Smoking
Diabetes
Being male
Chronic pancreatitis
Kidney
Tobacco smoking
High blood pressure
Von-Hippel-Lindau syndrome (VHL)
Leukemia
Radiation
Chemotherapy
Certain disease (Down syndrome)
Human T cell leukemia virus
Myelodysplatic syndrome

32. Race Twice as often as Africans Americans
Cancer Type
Risk Factor
Bladder
Occupation
Certain infection
Tobacco smoking
Race Twice as often as Africans Americans
Treatment with cyclophosphamide or arsenic
Uterine
Endometrial hyperplasia
Race Africans Americans
Hormonal replacement therapy
Obesity
Melanoma
Dysplastic nevi
Fai skin
Weakened immune system
Sever blistering/Sunburn
UV irradiation

34. STRATEGIES for CANCER CHEMOTHERAPY
A. Kill Cells by Necrosis-Current Strategy.
B. Kill Cells by Apoptosis ( “By-stander Effect”)
C. Induction of Terminal Differentiation.
D. Targeted Immunotherapy.
E. Gene Therapy.
F. Oncogene Inhibitors.
G. Inhibitors of Cell cycle Enzymes.
H. Telomerase Inhibitors.
I. Angiogenesis Inhibitors.

35. STRATEGIES for PREVENTION of CANCER
A. Prevention of “initiation” or Mutagenesis Phase Carcinogenesis.
B. Prevention of Promotion Phase of Carcinogenesis.
C. Prevention of Progression- Similar to Prevention of Initiation Phase.
D. Role of Diet( Tomatoes, Broccoli, Olive Oil, Green Tea).
E. Role of Cultural Behavior- Breast Cancer Example.
F. Role of Caloric Restriction- The Okinawa Example

36. 6. Eat fresh fruit and vegetables several times a day.
10 Rules to Avoid Cancer
1. Don’t smoke
2. Don’t smoke.
3. Don’t smoke.
4. Avoid exposure to other known carcinogens, including aflatoxin, asbestos and UV light.
5. Enjoy a healthy diet, moderate in calories,
salt and fat, and low in alcohol.
6. Eat fresh fruit and vegetables several times a day.
7. Be physically active and avoid obesity.
8. Have vaccination against, or early detection/treatment
of, cancer causing chronic infections.
9. Have the right genes.
10. Have good luck !

37. Diagnosis & Detection of Cancer
a) How can you detect cancer?
1. Change in bowel or bladder habit.
2. A sore that does not heal.
3. Unusual bleeding.
4. Nagging cough.

38. b) Routine Screening Tests
1. Self examination.
2. Examination by the physician
3. Breast cancer:
a) monthly breast self-examination.
b) annual medical check-up for women above 40 yrs.
c) mammography: X-ray examination of the breast to detect any lumps.

39. Features: 1-should be specific. 2-easily measured & cost effective.
c) Tumor Marker Tests
Tumor marker: a substance produced by host in response to presence of tumor.
Features: 1-should be specific.
2-easily measured & cost effective.
3-used for diagnosis &monitoring patient condition.
These are blood tests for tumor
e.g.:
• Prostate Specific Antigen (PSA):Test for prostate cancer.
• CA-125: Test for ovarian cancer.
• Alpha-fetoprotein (AFP): Test for liver cancer.