BIT 120
Copy of Cancer/HIV
Lecture
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
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.
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.
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
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
Tumors (Neoplasms)
Growing mass of tissue
New cells are being produced in
greater numbers than needed.
organization of the tissue becomes
disrupted.
Transformation
Definition:
Ø change of a normal cell into a cancerous one
due to a deregulation of growth
Ørate of cell proliferation has increased
What causes tumor
growth?
A. Proto-oncogenes
Ø proteins involved in growth and cell-cell
interactions
B. Viruses
Ø contain ONCOGENES
Cancer genes which cause cell
proliferation
despite signal saying ‘STOP’
Ø many cancers have no viral association
Insert into our chromosomes -Transforms
Epstein-Barr Virus
--> Burkitt’s Lymphoma
Papillomaviruses
--> cervical cancer
What causes Tumor
Growth?
C. Tumor Suppressor Genes
•Normal gene
prevents cells from dividing
•when mutated
loss of function
Cells divides Out of Control
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
ØTumor cells LOSE
•Contact Inhibition
•Density-dependent growth inhibition
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
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
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.
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
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
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
Where does Biotech
Come In?
1. Gene Therapy
2. Antisense Technology
3. Immunological Approaches
Gene Therapy
ðDeliver Killer genes
ðIssue: Selective Delivery
ðProcedure: Figure 14.5, p. 330
Genetically engineer retrovirus
with a gene encoding and envelope
protein specific for the cell receptor
of the Tumor cell
Antisense Technology
ØAdd antisense DNA to cancer cell
ØThis makes antisense mRNA
ØComplements with mRNA of oncogenes
ØAntisense mRNA would bind the sense
oncogene mRNA and prevent translation
of the oncogene
Immunological
Approaches
A. Tumor Infiltrating Lymphocytes (TILs)
Isolated from blood
Treated to proliferate -ILs
Reintroduce to body to fight tumor
ØCalled 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
Drug Trials for Cancer
• No Phase I – cytotoxic therapy
will make people sick
• Therapies allowed to be used
prior to launch- special
circumstances
• Placebo
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
HIV
• Results of T H cell depletion:
– opportunistic infections
– tumors develop
• HIV mutates rapidly
• HIV is a retrovirus – encodes
genome in RNA
• Member of lentivirus – “slow virus”
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
Progression of HIV Infection
Life Cycle of HIV
1. Virus attaches and penetrates host
cells- gp120 binds CD4 T H 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
Ø HIV high mutation rate impedes
immune response
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
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
Diagnosis of AIDS
• ELISA test
• Western Blot
• PCR test
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
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?)