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Medical informatics

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Title: Medical informatics


1
  • Medical informatics

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

3
Part1
  • Foundations

4
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

5
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)

6
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

7
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

8
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

9
Part2
Third World Diseases
10
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

11
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

12
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

13
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
14
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
15
Third world diseases
  • Asthma
  • Cystic fibrosis
  • Huntingtons disease
  • Sickle cell anemia
  • Malaria
  • Tuberculosis
  • Typhoid
  • HIV/AIDS
  • SARS

16
Main targets for drug design as per WHO report
Jan 2002
  • AIDS
  • Tuberculosis
  • Malaria

17
Life style drugs
  • Toe nail fungus
  • Obesity
  • Baldness
  • Face wrinkle
  • Erectile dysfunction
  • Separation anxiety of dogs, etc.

18
Part3
  • Cancer

19
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

20
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

21
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

22
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)

23
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

24
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

25
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

26
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

27
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

28
  • 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

29
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

30
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

31
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

32
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

33
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

34
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

35
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

36
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
37
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

38
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

39
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

40
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

41
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

42
Part4
  • Detailed Look into Cancers

43
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

44
Types of cancers known
  • lung
  • breast
  • thyroid
  • nerve system
  • muscles
  • genito-urinary system
  • leukemia
  • lymphoma
  • skin
  • brain
  • bone
  • gastrointestinal tract

45
Leukemias and lymphomas
  • Leukemias
  • Acute leukemia
  • Chronic leukemia
  • Lymphoma
  • Hodgkins lymphoma
  • Non-Hodgkins lymphoma

46
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

47
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

48
Cancer of the brain
  • Glioma
  • medullobastoma

49
Cancer of thyroid
50
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

51
Cancer of the lung
52
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

53
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

54
Neuroblastoma
55
Cancer of the muscles
  • Also known as rhabdomyosarcoma

56
Cancer of the bone
  • Osteogenic sarcoma
  • Ewings sarcoma
  • Multiple myeloma

57
Cancer of the skin
  • Squamous cells cancer (rodent ulcer)
  • Malignant melanoma

58
Part5
  • Response of Cancers to Chemotherapy

59
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

60
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

61
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

62
Leads to no benefit
  • Cancer of lung, squamous cell type
  • Cancer of colon
  • Cancer of the oesophagus
  • Cancer of skin or melanoma

63
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