1. Copy of Cancer/HIV Lecture
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.
Immune system can destroy if cell surface proteins are different enough from self to be detected

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
GOOD GENE undergoes mutation BAD GENE
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
*PROSTATE CANCER
prostate-specific antigen (PSA)
produced by cells of the prostate gland.
PSA circulates in the blood and can be detected and measured with a simple blood test.
*Other proteins
Proteases secretes in blood aid in detection
* Tumor cells
Since the 1930s, early detection using the Pap test has helped lower the death rate from cervical cancer more than 75 percent
MRI Examine internal organs without invasive surgery

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

25. high risk areas

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. HIV Human 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: HIV mutates rapidly
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?)