Transcript Document

Medical informatics
In this presentation……
Part 1 – Foundations
Part 2 – Cancer
Part 3 – Detailed Look into Cancers
Part 4 – Response of Cancers to
Chemotherapy
Part
1
Foundations
Bioinformatics and disease link
• Gene expression data analysis could give
important clues for reasons behind cause of
various diseases, especially about the
behaviour and growth of disease causing
germs
– Communicable diseases – malaria, typhoid,
cholera
– HIV/AIDS
– Cancer
– Dengue
smaller sets are preferred for
processing…
• Large samples of over 200 genes are not helpful since
if all of them are correlated with a particular class, it is
unlikely that they all represent different biological
mechanisms and hence are unlikely to add information
not already provided by others
• Though excellent research work has been carried out
in last three decades, there are no general approach for
identifying new cancer classes (class discovery) or for
assigning tumors to known classes (class prediction)
Some noted works
• Golub, Slonim et al (1999) published a paper on
molecular classification of cancer. This relates to
their study of class discovery and class prediction
by gene expression monitoring
• Slonim, Tamayo et al (2000) subsequently studied
class prediction and discovery using gene
expression data
• Ramaswamy et al (2001) brought out multiclass
cancer diagnosis using tumor gene expression
signature
The p53 protein
• One of the fly genes with a human counter part is p53,
a so-called tumor suppressor gene that when mutated
allows cells to become cancerous
• The p53 gene is part of a molecular pathway that
causes cells that have suffered irreparable genetic
damage to commit suicide
• It was identified that just as in human cells, fly cells in
which the p53 protein is rendered inactive, lose the
ability to self-destruct after they sustain genetic
damage and instead grow uncontrollably
DNA repair
• Using yeast genome, scientists discovered the
fundamental mechanism cells use to control how and
when they divide
• This has enlightened everyone about cell division and
DNA repair, processes that are important in cancer
diagnosis and control
• One of the findings is that the common
chemotherapeutic drug ‘cisplatin’ is particularly
effective in killing cancer cells that have s specific
defect in their ability to repair their DNA
Part
2
Third World
Diseases
Canadian team sequencing SARS virus
• Scientists from the Genome Science Centre at the
British Columbia Cancer Agency are sequencing
the Severe Acute Respiratory Syndrome (SARS)
virus
• 30 genome researchers from 11 countries are
involved in the project
• Early identification using electron microscopy,
PCR and viral microarray have identified the
SARS virus as a corona virus
AIDS tests have a flaw?…
• The ELISA and Western Blot tests look for the
antibodies to HIV in blood samples
• But these antibodies are also found in samples
of patients whose immune systems have been
activated by several other conditions – like
tuberculosis, multiple sclerosis and even warts
• These two tests actually look for the p24
protein which is found in healthy persons also
The HP virus
• After breast cancer, cervical cancer kills more
women each year than any other cancer
• It is particularly so in developing countries, where
screening is not widespread
• Lasting infection from certain strains of a common
sexually transmitted virus – human papilloma virus
(HPV) – causes almost all cervical cancers
• HPV was first linked to cervical cancer in 1983
• Infection most in women of age group 16-23 years
Scourge of the HP virus
USA
Developing
countries
World
wide
New cases
13,000
376,000
470,000
Deaths
4,100
192,000
232,000
Proportion of cancers worldwide linked to
papilloma virus infection
Types of cancer
Figures in %
Cervical cancer
99
Anal cancer
85
Cancer of vulva, vagina and penis
50
Third world diseases
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Asthma
Cystic fibrosis
Huntington’s disease
Sickle cell anemia
Malaria
Tuberculosis
Typhoid
HIV/AIDS
• SARS
Main targets for drug design as per
WHO report Jan 2002
• AIDS
• Tuberculosis
• Malaria
Life style drugs
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Toe nail fungus
Obesity
Baldness
Face wrinkle
Erectile dysfunction
Separation anxiety of dogs, etc.
Part
3
Cancer
Cancer
• It has existed all along with man
• Twenty-five centuries ago, Hippocrates, called
it karkinois because the swollen blood vessels
going and coming from the tumor mass, gave
the appearance of the claws of a crab
• Susruta described cancer as a tumor which
would ulcerate and would not cure, and “sow
its seeds in other parts of the body”
Cancer treatment
• Cancer being more common in older people,
increasing life span of man is providing more
and more candidates for getting the disease
• Surgery to treat it has been used since centuries
ago
• Radiation was used to treat breast cancer within
one year of Roentgen’s discovery
• World War II provided the first drug in the form
of nitrogen mustard to kill cancer cells
Cancer cause
• Cancer arises from the abnormal and uncontrolled
division of cells, known as cancer cells, that then
invade and destroy the surrounding tissues
• Cancer cells, in other words, refuse to stop
multiplying and continue to increase in number
• It is the failure to stop multiplying which is the
hallmark of cancer
• This they do even at the cost of other normal cells of
body which are starved to death for lack of nutrition
Physico-chemical causes of cancer
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Benza pyrene (found in coal, tar, etc.)
Asbestos causes mesothelioma, cancer of the pleura
Dyes, synthetic colors
Aromatic amines, polycyclic aromatic hydrocarbons
Urethane
Metals like nickel, chromium, arsenic, beryllium
Harmones
Aflatoxin, pesticides, insecticides
Diethy stilbesterol (medicinal compound/female sex
harmone)
Other causes of cancer
• Genetic and personal factors – age, sex,
race, marital status, heredity, socioeconomic status
• Immune deficiency
• Environmental
• Virus, e.g., polyoma virus causes leukemia
Cancer cells vs. normal cells
• Cancer cells are different from normal cells in some
aspects
• They do not remain confined to one part of the body
• They penetrate and infiltrate into the adjoining tissues
and dislocate their function
• Some of the cancer cells get detached from the main
mass or site of origin and travel by blood cell and
lymph channels to sites distant from the original tumor
and form fresh colonies, called metastasis or secondary
growths, in other organs where they grow at the cost of
the normal cells
• This is how they destroy the well-regulated functioning
of the body and bring about its end
Fast and slow-growing cancers
• A cancer may be slow- or fast-growing
• The rate of growth depends on the tissue in which it
occurs and also on the inherent character of the type
of cancer
• Rapidly growing cancers are those which send
metastasis in other organs, are much more dangerous
• Sometimes the primary cancer in the first stage of
development grows slowly, as for example, that of the
stomach and remains unnoticed, while the secondaries
spread rapidly in the liver, abdominal lymph glands,
etc. These secondary cancers are first noticed
Tumor
• Growth of cancer cells leads generally to formation of
a nodule or tumor; hence cancer is also called a tumor
• If it is superficial, it is firm to touch, gets fixed to
surrounding tissues and is not freely moveable
• However, every nodule is not cancer
• Some like warts, cysts, or adenomas are benign and
are easily treated
• But in order to be sure whether a nodule is cancerous,
a bit of the nodule is taken and examined under the
microscope, which generally gives a correct diagnosis
How does cancer spread?
• Cancer spread occurs through any or all of the
three routes
– Local spread: cancer infiltrates the adjoining
parts, organs, tissues, etc.
– Lymphatic spread: the lymph glands or nodes
trap the cancer cells present in the lymph fluid and
cancer grows within them. Progressive spread
along lymph vessels and glands may occur and in
the process quite distant glands may become
involved
– Bloodstream spread: if cancer invades blood
vessels then the cancer cells may break into the
bloodstream and be carried to other parts of the
body and settle over there, producing secondary
cancers. The major site of spread in cases of
bowel cancer is liver. The lungs are the
commonest site of metastasis from other cancer
sites. The spread to many other organs is also
common
Is cancer inherited?
• There are cases of some families, several
members of which have suffered from cancer
• Scientists have propagated some strains or
breed of mice in which a large number of
males developed lung cancer and over 90
percent of females breast cancer
• A careful analysis of data shows that certain
types of cancer are hereditary and there is a
likelihood of cancer of a particular tissue or
organ developing in the descendants of
persons who have suffered from cancer
Cancer cure is expanding…
• In the 1950s, only 30 percent cancers were
curable
• By 1977, that percentage had risen to 41
• By 1980, 45 percent of all serious cancers
were curable
• This percentage is increasing fast
Fighting cancer
• Fighting cancer is not just hoping to
discover a “magic bullet” to annihilate it
• It is much broader a problem
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Early detection
Curative measures
Rehabilitation of the patients
Psychological problems faced by the patient
and relatives
Support sciences
• Interpretation of tumor data would involve an
experienced hematophothologist for tumor
morphology, histochemistry and immunophenotyping
analysis
• Histopathology is the science that studies pathologic
tissues. Just as in the case of all other branches of
biological sciences, bioinformatics is poised to bring
monumental changes to this branch as well. It is
expected that it would also greatly influence the
cancer pathogenesis and pharmacology
Support sciences
• It was found that genes useful for cancer class
prediction may also provide insights into cancer
pathogenesis and pharmacology
• The National Cancer Institute in USA maintains a
project called Human Tumor Gene Index. More
than 50,000 genes active in one or more cancers
have been identified; with over 6,000 genes active
in breast cancer cells, 277 that are not active in
other tissues
Signs and symptoms
• Cancers of various types and at various sites
manifest themselves in a variety of ways
• On external surface, any thickening of the
tissues, formation of nodule or tumor,
persisting sores and ulcers, can be feature of
cancer
• Internal cancers may grow for some time
before they cause any symptom. But weight
loss, anaemia and low-grade fever in older
people even without any other symptom,
should arouse suspicion
Any manifestation may be cancer…
• A lump or hard area in the breast
• A change in a wart or mole
• A persistent change in digestive and bowel
habits, e.g. constipation
• A persistent cough or hoarseness in a smoker
• Bleeding of vagina at times other than the
menstrual
• Non-injury bleeding from the surface of skin,
mouth of any other bodily orifice
• Any ulcer that does not get well
• Unexplained loss of weight
• Unexplained diminished or lost appetite
• Unexplained low-grade fever
Cancer in children
Type
% of total cancers
Leukemia
Nervous system (retinoblastoma)
Bone sarcoma
Soft tissue sarcoma
30
12
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12
Neuroblastoma
Wilms’ (kidney) tumor
Lymphoma
10
8
8
Hodgkin’s disease
Others
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Cancer on older people
• Cancer occurs more often in people after 50
or 60 years of age
• In still older people, i.e. 80 years or above,
some characteristics of cancer have been
noted during life and in post-mortem studies
of people who have died of causes other
than cancers
Cancer in older people
• Small microscopic cancers of the prostate were very
common in males
• Lung and stomach cancer were seen in many cases
both in males and females
• Lung cancer of the type of adenocarcinoma, was
found often and was commoner in females than males
• Multiple cancers arising in different organs at the
same time was not an uncommon feature
• Lesions regarded as precursors to cancers were often
observed in stomach, colon and lungs
• The rate of growth of cancers in general was slow
Cancer situation in the World
• Cancer is the second common cause of death in
the developed countries next to cardiovascular
(heart and blood vessel) disease
• In Europe and North America, approx. 1-5 die of
cancer
• According to WHO, out of an estimated total of 50
million are attributed cancer, and the number of
deaths from cancer throughout the world is
increasing
Cancer situation in India
• Approx. 500,000 new cases of cancer occur every
year in India
• As the human life span is increasing in India, more
cases of cancer are observed here also
• Cancer is thus regarded as an emerging health
problem in India
• According to Dr. D J Jussawalla, Indian Cancer
Society, “Cancer is one of the 10 leading causes of
death today in India, and is advancing in rank year
by year”
Indian scenario
• The figures given by Indian Cancer Society
state that about 1.5 million people suffer
from cancer at any given point of time in
India
• Oral cancer and cervix cancer account for
the major causes of cancer in this country
Part
4
Detailed Look into
Cancers
Broad groups of cancers
• Carcinoma – any cancer that arises in epithelium,
tissue that lines the skin and internal organs of the body
• Sarcoma – any cancer of connective tissue. These
tumors may occur in any part of the body, as they arise
in the tissues that make up an organ rather than being
restricted to a particular organ. They can arise in
fibrous tissue, muscle, fat, bone, cartilage, blood and
lymphatic vessel, etc.
• Leukemia – it is a cancer of the blood in which the
bone marrow and other blood forming organs overproduce immature or abnormal white cells
• Lymphoma – any malignant tumor of lymph nodes or
lymph gland
Types of cancers known
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lung
breast
thyroid
nerve system
muscles
genito-urinary
system
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leukemia
lymphoma
skin
brain
bone
gastrointestinal
tract
Leukemias and lymphomas
• Leukemias
– Acute leukemia
– Chronic leukemia
• Lymphoma
– Hodgkin’s lymphoma
– Non-Hodgkin’s lymphoma
ALL/AML
• AML affects various white blood cells including granulocytes,
monocytes and platelets
• Leukemic cells accumulate in the bone marrow, replace normal blood
cells and spread to the liver, spleen, lymph nodes, central nervous
system, kidneys and gonads
• ALL is a cancer of immature lymphocytes, called lymphoblasts
(sometimes called as blast cells). Normally, white blood cells repair and
reproduce themselves in an orderly and controlled manner but in
leukemia the process gets out of control and the cells continue to divide,
but do not mature
• ALL is further divided into two subcategories viz., T-lineage ALL and
B-lineage ALL
Mix of cancers
• The cases become extremely complex when one type of
cancer pretends to be another or when a mix of cancers
accidentally is identified as cancer of only one type
• Some particular subtypes of acute leukemia have been
found to be associated with specific chromosomal
translocation
• The samples for testing cancer or leukemia comprises of
bone marrow and peripheral blood samples and thereafter
RNA prepared from bone marrow or blood cells would be
hybridized
Cancer of the brain
• Glioma
• medullobastoma
Cancer of thyroid
Cancers of gastro-intestinal tract
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Cancer of the mouth
Cancer of the oesophagus
Cancer of the stomach
Cancer of the colon and rectum
Cancer of the liver
Cancer of the gall-bladder
Cancer of the pancreas
Cancer of the lung
Cancer of the breast
• The genes BRCA1 and BRCA2 are linked to
breast and ovarian cancer, whereas the MLH1
gene on human chromosome 3 is associated with
colon cancer and MMAC1 gene mutates to
generate a protein responsible for brain and
prostate cancer
Cancers of genito-urinary system
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Cancer of the uterine cervix
Cancer of the uterus
Cancer of the ovary
Chloriocarcinoma
Cancer of the testes
Cancer of the prostate
Cancer of the penis
Cancer of the urinary bladder
Cancer of the kidney
– Hyperneproma
– Wilm’s tumor
Neuroblastoma
Cancer of the muscles
• Also known as rhabdomyosarcoma
Cancer of the bone
• Osteogenic sarcoma
• Ewing’s sarcoma
• Multiple myeloma
Cancer of the skin
• Squamous cells cancer (rodent ulcer)
• Malignant melanoma
Part
5
Response of Cancers to
Chemotherapy
Leads to cure
• Blood cancer or acute lymphoblastic leukemia in
children
• Cancer of lymphatic system or Burkitt’s lymphoma
• Hodgkin’s disease – a malignant tumor of
lymphatic system
• Wilm’s tumor or tumor of kidney common in
children
• Cancer of muscle or rhabdomyosarcoma
• Cancer of testes or teratoma
• Cancer of the placenta or choriocarcinoma
• Cancer of bone common among children or
Ewing’s sarcoma
Leads to prolongation of life
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Cancer of breast
Cancer of the ovaries
Cancer of lung, small-cell anaplastic type
Non-Hodgkin’s lymphoma
Chronic lymphocytic leukemia
Acute myeloid leukemia
Brain cancer or medulloblastoma
Leads to marginal benefit
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Cancer of stomach
Cancer of the pancreas
Bone cancer or myeloma
Soft tissue arcoma
Cancer of urinary bladder
Cancer of thyroid
Leads to no benefit
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Cancer of lung, squamous cell type
Cancer of colon
Cancer of the oesophagus
Cancer of skin or melanoma