BIT 120

1. BIT 120 Copy of Cancer/HIV Lecture

2. Cancer • DEFINITION • Any abnormal growth of cells that has malignant potential • i.e.. Leukemia • Uncontrolled mitosis in WBC • Genetic disease caused by an accumulation of mutations over a lifetime • not inherited (may exhibit strong predisposition); disease of elderly These cells can form a TUMOR –localized, abnormal, growing mass of tissue not normally found in portion of body Tumors can metastasize-cells break of from original mass; enter bloodstream-move to other parts of body; this called CANCER

3. Loss of Normal Growth Pattern • TWO CAUSES • 1. uncontrolled cell growth • 2. loss of a cell's ability to undergo "apoptosis." • Apoptosis • "cell suicide" or • “programmed cell death” • the mechanism by which old or damaged cells normally self-destruct.

5. Classes of Cancer Cancer can originate almost anywhere in the body. Carcinomas the most common types of cancer arise from the cells that cover external and internal body surfaces. Lung, breast, and colon Sarcomas arise from cells found in supporting tissues bone, cartilage, fat, connective tissue, and muscle.

6. Types of Cancer Lymphomas arise in the lymph nodes and tissues of the body's immune system. Leukemias immature blood cells that grow in the bone marrow and tend to accumulate in large numbers in the bloodstream. Uncontrolled mitosis in white blood cells

8. Naming Cancers TABLE 14.1, p. 314 Names are created by using different prefixes that stand for the name of the cell type involved. prefix "osteo” = bone osteosarcoma - cancer of bone prefix "adeno" = gland, adenocarcinoma - cancer of gland cells/breast

9. Tumors (Neoplasms) Growing mass of tissue New cells are being produced in greater numbers than needed. organization of the tissue becomes disrupted.

10. Transformation • Definition: • change of a normal cell into a cancerous one due to a deregulation of growth • rate of cell proliferation has increased

11. What causes tumor growth? • A. Proto-oncogenes • proteins involved in growth and cell-cell interactions • B. Viruses • contain ONCOGENES • Cancer genes which cause cell proliferation • despite signal saying ‘STOP’ • many cancers have no viral association • Insert into our chromosomes -Transforms Epstein-Barr Virus --> Burkitt’s Lymphoma Papillomaviruses --> cervical cancer

12. What causes Tumor Growth? • C. Tumor Suppressor Genes • Normal gene • prevents cells from dividing • when mutated • loss of function • Cells divides Out of Control

13. Traits of Tumor Cells • A. Distinctive Appearance • loss of orientation • different shape • B. Immortal in culture • C. Interact with neighboring cells differently from • normal cells • Tumor cells LOSE • Contact Inhibition • Density-dependent growth inhibition

14. Traits of Tumor Cells • D. Do Not attach to surfaces • E. Altered cell surfaces • different proteins in plasma membrane • F. May have chromosomal mutations • Figure 14.2, p.317 • G. Secrete proteins • Growth factors to make blood vessels for ANGIOGENESIS • Proteases

15. Microscopic Appearance • Cancer cells have Distinctive appearance • a large number of dividing cells • variation in nuclear size and shape • variation in cell size and shape • loss of specialized cell features • loss of normal tissue organization

17. Malignant vs. Benign Benign tumors that cannot spread by invasion or metastasis; hence they only grow locally. Malignant tumors that are capable of spreading by invasion and metastasis. ”Cancer" applies only to malignant tumors.

18. Diagnosis 1. Blood Tests 2. PAP test microscopically observe cervical cells 3. Biopsy surgical removal of a small piece of tissue for microscopic examination. 4. Genetic Diagnosis Screen for oncogene or tumor suppressor mutations 5. MRI Magnetic Resonance Imaging

19. Treatments • Remove mass surgically • need to remove before tumor has done damage to organ • Chemotherapy – • chemicals used to destroy mitotically dividing cancer cells • Table 14.3, p. 327 • Radiation – • use X-rays or gamma rays to kills cancer cells • ONLY chemotherapy works for metastasizing tumors

20. Side Effects • Lowers immune response • no increase in WBC • need antibiotics • Intestinal Disorders • Nausea • Vomiting • Loss of hair • Side affects result because treatment prefers • ACTIVELY DIVIDING CELLS

21. Where does Biotech Come In? 1. Gene Therapy 2. Antisense Technology 3. Immunological Approaches

22. Gene Therapy • Deliver Killer genes • Issue: Selective Delivery • Procedure: Figure 14.5, p. 330 Genetically engineer retrovirus with a gene encoding and envelope protein specific for the cell receptor of the Tumor cell

23. Antisense Technology • Add antisense DNA to cancer cell • This makes antisense mRNA • Complements with mRNA of oncogenes • Antisense mRNA would bind the sense oncogene mRNA and prevent translation of the oncogene

24. Immunological Approaches • A. Tumor Infiltrating Lymphocytes (TILs) • Isolated from blood • Treated to proliferate -ILs • Reintroduce to body to fight tumor • Called adoptive immunotherapy B. Magic Bullets monoclonal antibodies (against Tumor cell antigen) conjugated to toxin MOST of these treatment require that you ‘know’ the tumor cell antigens/receptor

26. Drug Trials for Cancer • No Phase I – cytotoxic therapy will make people sick • Therapies allowed to be used prior to launch- special circumstances • Placebo

27. HIVHuman Immunodeficiency Virus • Virus that causes AIDS (acquired immune deficiency syndrome) • 30 to 40 million infected • Prolonged infection • Primary effect of HIV infection: reduction in TH cells

28. HIV • Results of TH cell depletion: • opportunistic infections • tumors develop • HIV mutates rapidly • HIV is a retrovirus – encodes genome in RNA • Member of lentivirus – “slow virus”

29. HIV • Lentivirus: • Persist lifelong • High mutation rates • Variation in disease presentation • Variation in time of onset of disease • Infect non-diving cells • 3 infection stages • acute • latent • high levels of viral production

31. Progression of HIV Infection

33. Life Cycle of HIV 1. Virus attaches and penetrates host cells- gp120 binds CD4 TH cells 2. Viral RNA converts to viral DNA 3. Viral DNA integrates into human chromosome 4. Infected host cells produce new virus particles 5. New virus particles bud from host cell one-by-one, taking host cell's membrane along as envelope • HIV high mutation rate impedes immune response

34. Development of HIV Disease Time Periods: 1. weeks 1-3: virus enters body, circulates, and makes infected person contagious 2. weeks 1-8: acute viral syndrome • short term • mild or severe flu-like symptoms • fever, fatigue, rash, aching muscle and joints, sore throat, enlarged lymph nodes

35. Development of HIV Disease (cont’d) 3. 6 weeks - 6 months +: positive HIV antibody test • seronegative: negative test • seropositive: positive test for HIV 4. 2 yrs: onset of longer-lasting symptoms 5. 6 months-15 yrs: development of AIDS

36. Diagnosis of AIDS • ELISA test • Western Blot • PCR test

37. HIV Therapy Strategies • Boosting immune response insufficient • Interfere with: • HIV attachment to Cells • HIV integration into the host cell genome • Virus replication • Assembly of new virus particles

38. Possible HIV Therapies • Preventing assembly of HIV virus • HIV protease • Inhibit reverse transcription • AZT (azidothymidine) • Other nucleotide analogs • Gene Therapy • Antisense RNA • Introduce into stem cells • Preventing entry of HIV into uninfected cells • gp120/viral envelope • CD4 on the cell surface • Vaccines – recombinant or attenuated virus (risky?)