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Medical informatics

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.

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Medical informatics

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  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

  14. Proportion of cancers worldwide linked to papilloma virus infection

  15. Asthma Cystic fibrosis Huntington’s disease Sickle cell anemia Malaria Tuberculosis Typhoid HIV/AIDS SARS Third world diseases

  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 Roentgen’s 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

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

  45. Leukemias and lymphomas • Leukemias • Acute leukemia • Chronic leukemia • Lymphoma • Hodgkin’s lymphoma • Non-Hodgkin’s 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

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