Medical informatics

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• Medical informatics

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In this presentation

• Part 1 Foundations
• Part 2 Cancer
• Part 3 Detailed Look into Cancers
• Part 4 Response of Cancers to Chemotherapy

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Part1

• Foundations

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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

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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)

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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

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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

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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

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Part2
Third World Diseases
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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

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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

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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

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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
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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
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Third world diseases

• Asthma
• Cystic fibrosis
• Huntingtons disease
• Sickle cell anemia
• Malaria
• Tuberculosis
• Typhoid
• HIV/AIDS

• SARS

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Main targets for drug design as per WHO report
Jan 2002

• AIDS
• Tuberculosis
• Malaria

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Life style drugs

• Toe nail fungus
• Obesity
• Baldness
• Face wrinkle
• Erectile dysfunction
• Separation anxiety of dogs, etc.

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Part3

• Cancer

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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

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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 Roentgens discovery
• World War II provided the first drug in the form
  of nitrogen mustard to kill cancer cells

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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

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Physico-chemical causes of cancer

• 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)

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Other causes of cancer

• Genetic and personal factors age, sex, race,
  marital status, heredity, socio-economic status
• Immune deficiency
• Environmental
• Virus, e.g., polyoma virus causes leukemia

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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

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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

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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

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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

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• 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

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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

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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

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Fighting cancer

• Fighting cancer is not just hoping to discover a
  magic bullet to annihilate it
• It is much broader a problem
• Early detection
• Curative measures
• Rehabilitation of the patients
• Psychological problems faced by the patient and
  relatives

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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

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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

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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

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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

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Cancer in children
Type of total cancers
Leukemia 30
Nervous system (retinoblastoma) 12
Bone sarcoma 12
Soft tissue sarcoma 12
Neuroblastoma 10
Wilms (kidney) tumor 8
Lymphoma 8
Hodgkins disease 6
Others 2
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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

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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

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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

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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

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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

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Part4

• Detailed Look into Cancers

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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
  over-produce immature or abnormal white cells
• Lymphoma any malignant tumor of lymph nodes or
  lymph gland

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Types of cancers known

• lung
• breast
• thyroid
• nerve system
• muscles
• genito-urinary system

• leukemia
• lymphoma
• skin
• brain
• bone
• gastrointestinal tract

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Leukemias and lymphomas

• Leukemias
• Acute leukemia
• Chronic leukemia
• Lymphoma
• Hodgkins lymphoma
• Non-Hodgkins lymphoma

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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

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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

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Cancer of the brain

• Glioma
• medullobastoma

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Cancer of thyroid
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Cancers of gastro-intestinal tract

• 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

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Cancer of the lung
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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

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Cancers of genito-urinary system

• 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
• Wilms tumor

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Neuroblastoma
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Cancer of the muscles

• Also known as rhabdomyosarcoma

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Cancer of the bone

• Osteogenic sarcoma
• Ewings sarcoma
• Multiple myeloma

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Cancer of the skin

• Squamous cells cancer (rodent ulcer)
• Malignant melanoma

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Part5

• Response of Cancers to Chemotherapy

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Leads to cure

• Blood cancer or acute lymphoblastic leukemia in
  children
• Cancer of lymphatic system or Burkitts lymphoma
• Hodgkins disease a malignant tumor of
  lymphatic system
• Wilms 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 Ewings
  sarcoma

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Leads to prolongation of life

• Cancer of breast
• Cancer of the ovaries
• Cancer of lung, small-cell anaplastic type
• Non-Hodgkins lymphoma
• Chronic lymphocytic leukemia
• Acute myeloid leukemia
• Brain cancer or medulloblastoma

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Leads to marginal benefit

• Cancer of stomach
• Cancer of the pancreas
• Bone cancer or myeloma
• Soft tissue arcoma
• Cancer of urinary bladder
• Cancer of thyroid

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Leads to no benefit

• Cancer of lung, squamous cell type
• Cancer of colon
• Cancer of the oesophagus
• Cancer of skin or melanoma

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