Presentation on theme: "Cancer By Dr. El Hassan Mokhamer. What is cancer? Abnormal cell growth (neoplasia) Malignant as opposed to benign – Benign:- slow growth, non-invasive,"— Presentation transcript:
Cancer By Dr. El Hassan Mokhamer
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
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
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
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.
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.
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.
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.
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
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)
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.
Epigenetic Carcinogens or Tumor Promoters:- 1. Non-Mutagenic chemicals( e.g., DDT, Phenobarbital). 2. They Act as Either Mitogens and / or Inhibitors of Apoptosis.
IV.ONCOGENE/ TUMOR SUPPRESSOR GENE THEORY -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. 1. ONCOGENES
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)
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
NecrosisApoptosis Cell swellingCell Shrinkage Loss of membrane integrity Membrane integrity remains intact No energy requiredEnergy requiring Groups of cellsSingle cells
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
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. Characteristics of Cancer Cells.
Mutagens Viruses: insertional mutagenesis Chemicals: DNA adducts UV and ionizing radiation: single and double strand DNA breaks
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).
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
What causes cancer?
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 Risk Factor
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).
Risk Factor/ Cancer Type Cancer TypeRisk Factor Lung CancerTobacco smoke Radon Asbestos and other substances Air pollution BreastRadiation Genetic changes (Inherited mutation) ColorectalCancer polyp Genetic alteration Diet Cigarette smoking Ulcerative colitis or chon's disease ProstateDiet Certain prostate changes Race Africans Americans
Cancer TypeRisk Factor LiverHepatitis viruses (HCV.HBV) PancreasSmoking Diabetes Being male Chronic pancreatitis KidneyTobacco smoking High blood pressure Von-Hippel-Lindau syndrome (VHL) LeukemiaRadiation Chemotherapy Certain disease (Down syndrome) Human T cell leukemia virus Myelodysplatic syndrome
Cancer TypeRisk Factor BladderOccupation Certain infection Tobacco smoking Race Twice as often as Africans Americans Treatment with cyclophosphamide or arsenic UterineEndometrial hyperplasia Race Africans Americans Hormonal replacement therapy Obesity MelanomaDysplastic nevi Fai skin Weakened immune system Sever blistering/Sunburn UV irradiation
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.
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
10 Rules to Avoid Cancer 2. Dont smoke. 3. Dont smoke. 4. Avoid exposure to other known carcinogens, including aflatoxin, asbestos and UV light. 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 ! 5. Enjoy a healthy diet, moderate in calories, salt and fat, and low in alcohol. 1. Dont smoke
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.
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.
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.