biochemistry of cancer cell - الكيمياء الحيوية للجميع · pdf...
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Prof. Taha Kumosani
Biochemistry of Cancer Cell
Prof. Taha Kumosani
http://biochemistry4all.com/Taha/5.htm
Cancer: an Overview
Paleopathologists – Dinosaur bones
Egyptians – Papyrus
– Autopsis
Hippocrates – Carcinoma
– Carcinos: Benign tumors
Hemorrhoids
Chronic ulcerations
History of Cancer
Galen, Bichat, Muller, Pasteur, Laonnec, Cohnheim and Virchow
Theories: Irritation
Embryonal
Infections
Cancer theories of the 20thCentury
Otto Warburg: abnormal cell respiration
Jesse Greenstein: tumor metabolism
Principal theories of cancer formation:
Genetic [addition (v), alteration or subtraction (c or r)
Non genetic
What is Cancer? •J. Ewing definition:
"Neoplasm: is a relatively autonomous growth of tissue"
•Neoplasm
•Cancer: malignant neoplasm
•Tumor: a general term indicating any abnormal mass or growth of
tissue
Classification
A. Benign tumors
B. Malignant (metastasize, abnormal chromosome number)
Benign tumors: do not spread from their site of origin, e.g. brain tumor, warts
Metastasis : a secondary growth originating from the primary and growing elsewhere in the body
Characteristics of Benign tumours
1. Localized growths respond to body’s
homeostatic controls
2. Encapsulated
3. Stop growing when they meet a boundary
of another tissue
4. Can be destructive
Characteristics of Malignant
1. Have aggressive growth, rapid cell division
outside the normal cell cycle
2. Not under body’s homeostatic controls
3. Cut through surrounding tissues causing
bleeding, inflammation, necrosis (death) of
tissue
Malignant can metastasize
Embryologic Basis of Nomenclature
The suffix "oma" mean tumor
(Exception are the terms, granuloma: a growth of inflammatory tissue, and hematoma: a mass of blood outside vessels in a tissue)
Benign tumors: tissue(prefix) and (suffix)-oma
Cancers are divided in 2 general categories depending on their embryologic origin:
Ectodermal cells form skin, its appendages and nerve tissues (carcinoma)
Mesodermal cells form bone, muscle, cartilage and related tissues (sarcoma)
Endodermal cells form the intestinal system and its associated organs (carcinoma)
Example:
Adonocarcinoma [adeno-, glandular (tissue); carcinoma, arising
from endodermal tissue of the stomach, pancreas, or breast]
Caricnosarcoma (indicate that tumor was derived from two
embryonic layers)
Teratoma (indicate that tumor was derived from the three
embryonic layers)
Normal cell cycle
divides grows functions
apoptosis death
Cancer cell cycle
divides grows
immortal
tumor
Apoptosis : programmed cell death that happens in all normal cells,
but not in cancer cells
Growth and Spread
Cancer Growth and Spread
Development of metastasis
Mechanisms of cell invasion
Mechanisms of cancer spread
Immunity to metastasis
Cancer is a label for collection of distinct but related
disease
Characteristics of malignant
1. Grow rapidly
2. Invade other tissue
3. Rarely encapsulated
4. Contain many abnormal cells of different sizes and shapes
Characteristics of malignant cells
Characteristics of malignant cells
1. Loss of stickiness
2. Increased mobility
3. Proteolytic enzyme
4. Altered cell surface
Mechanisms of Cancer Spread
Three major routes:
1. Direct extension or transplantation
2. Lymphatic system
3. Blood system
Common cancer sites
Brain Tumor
Lung Cancer (Bronchogenic Carcinoma)
Thyroid Gland Cancer
Pancreatic Cancer
Colon and Rectum Cancer
(Colorectal Cancer)
Breast Cancer
Uterine Cancer (Endometrial Cancer)
Ovarian Carcinoma
Cervical Carcinoma
Prostate Cancer
Testicular Cancer (Carcinoma Of The Testes)
Skin Cancer - Several Types
(Malignant Melanoma)
Renal Cell Carcinoma
Squamous Cell Carcinoma
Leukemia
Lymphoma
Cancer & Radiation Cancer – Causing Radiation Ionizing radiation
Dose – Response : how much Radiation?
Animals studies
Human studies
Problems in assessing radiation for humans
How low dose rates affect man
How ionizing radiation induces tumor – still unknown
Public policy toward radiation
Dose and Tissue
Minimum dose in human
Type of Radiation:
Ionizing
Nonionizing
Carcinogens agents which cause cancer in industrial products
Pesticides
Water supplies
Foods
Cosmetics
% of human cancer caused by environmental
carcinogens
Relation between cancer incidence and types
and different environment around the world
How much cancer is caused by any particular
agents?
Carcinogens Include
- Polycyclic aromatic hydrocarbon
- Aromatic Amines
- Aminoazodyes, dialkylnitrosamine, and alkylating
agents (used in industry as intermediate)
-Natural Products
Aflatoxin, formed by the fungus Aspergillus flavus
Carcinogenicity of Aflatoxin
* Species
* Dose
Naturally produced chemicals
Miscellaneous
- Inorganic Carcinogenic
Beryllium, Cadmium, Chromium, Nickel and
lead compounds
Radioactive elements such as Uranium, Radium
and Thorium
Asbestos (shape and size)
Virus: is a small infectious agent that can replicate
only inside the living cells of organisms
An oncovirus: is a virus that can cause cancer
Cancer and viruses
Retrovirus enters host cell
What is a hormone?
Hormones are naturally occurring substances
that are produced in specific parts of our bodies and act as chemical messengers. They travel through the blood to control the functions of other tissues and organs
Some of the best known hormones are estrogen and testosterone. These are known as ‘sex hormones’ and perform a variety of functions all around our bodies
Hormones affect growth and differentiation
Hormonal imbalance influence the incidence, location and rate of cancer growth
Hormonal imbalance may be produced by injecting hormones, explanting or destroying the endocrine gland or administering hormonal antagonists
What affects our hormone levels?
Reproductive factors
Lifestyle changes
External sources
Drugs that lower hormone levels
Heredity: is the passing of traits to offspring
(from its parent or ancestors).
Cancer and heredity
A hereditary disease is a disease caused by an
abnormality in an individual's DNA which is
inherited genetically
But in some cases the cancer is caused by an
abnormal gene that is being passed along from
generation to generation. Although this is often
referred to as inherited cancer
Why alteration in gene is a problem?
How to identify hereditary cancer?
It is mostly genetic testing that helps one to
assess the hereditary cancer risk
Additionally, identification of gene mutations
also helps other family members to determine
whether they share hereditary cancer risks
Genetic testing is mostly done using blood
Xeroderm pigmentosum
familial polyposis
A molecular basis of cancer
A molecular basis of cancer:
Introduction
Pleiotropy
A genetic basis
Abnormal chromosome
Cancer Cell
Normal Chromosome
Cancer phenotype (total set of structural and functional characteristics that define a cancer cell) raise important questions
Marguerite Vogt and Renato Dulbecco – California Institute of Technology
A genetic basis:
* Carcinogens act by damaging DNA and thus causing gene
mutations
* History exp. More than 50 years ago, demonstrated the central role of DNA as a carrier of genetic information, Oswald and Colin M.
* Macleod and Maclyn McCarty – Rockefeller Institute for Medical Research
Affecting cell signalling
• All normal cells receive specific signals that trigger
programmed cell death
• Some chemicals destroy these signals
• As a result the cells do not receive the signals that start cell
death
• Hence they keep growing causing cancer
Destruction of error repair mechanisms:
Every normal cell has DNA repair genes
These genes correct any defects that occur sometimes during DNA
replication and cell growth in normal cells
These genes are called uvr and rep genes
Some carcinogens affect the repair genes
As a result, these genes do not function and do not correct errors in
the cell, leading to abnormal growth, division and cancer
Tests and diagnosis
Some important tests for diagnosis
cancer
1. A process of elimination
2. The basic tests
3. Seeing inside by sound and heat
4. X-rays: new refinements of an old tool
5. Tracing tumor with hot atoms
6. The answer in a tissue sample
When initially diagnosed with cancer, a cancer
specialist, an oncologist, will provide you with
the cancer treatment options
He or she will recommend the best treatment
plan based on your type of cancer, how far it has
spread, and other important factors like their age
and general health
Treatments
I. Chemotherapy
II. Hormaone Therapy
III. Immunotherapy
IV. Growth factor
V. Radiotherapy
VI. Surgery
VII. Natural therapy
Coping with Cancer
A new way to speak
After breast surgery, a normal life and appearance
Countering the side effects of drugs and rays
How patients help patients
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