Download Week_1 - Denver School of Nursing

Denver School of Nursing – ADN & BSN Programs
No Laboratory component for this class
BIO 206 & 308 – Day 1 CH1– 3 Alteration to Cellular Bio & Genetic Path
Intro’s – Please Share with us:
1) What is your name?
2) What city have you resided in the longest?
3) Who or what event influenced you most to enter
the field of nursing?
4) What field of nursing do you want to work in?
5) What is your favorite pathological condition?
For the first “warm up” day of Patho we are going
to cover:



1) Cellular Biology - Ch. 1
2) Genes and Genetics Diseases - Ch. 2
3) Altered Cell / Tissue Bio - Ch. 3
This whole chapter is a brief summary and
review from Anatomy and Physiology

LETS See how much you remember…

LETS See how much Cell Bio you remember…
~ What are the metaphors for the following
images????

What cellular structure does this represent?
Source: http://news.parcel2go.com

What cellular structure does this represent?
Source: http://googleimages.com

What cellular structure does this represent?
Source: http://www.itchmo.com

What cellular structure does this represent?
Source: http://www.itchmo.com

The “Circle of Cellular Life”

What cellular structure does this represent?
Source: http://www.itchmo.com

What cellular structure does this represent?
Source: chipotle.com

LETS See how much you remember…
~ What is the diff between Prokaryotes & Eukaryotes?
~ Membrane composition
- Why are Proteins / lipids important?
- Endoplasmic reticulum
- Ribosomes
- Golgi complex
- Lysosomes
- Peroxisomes
- Mitochondria
- Cytoskeleton (microtubules + actin)
Source: Huether, McCance Understanding Pathophysiology 4th Ed. 2008
~ What are the diff types of cellular signaling?
~ What are the diff types of cellular signaling?
1) Autocrine
2) Paracrine
3) Hormonal
4) Neurotransmitter
5) Neurohormonal secretion
6) Diffusion vs Transport
What are the
Different types
of cellular signaling?
Source: Huether, McCance Understanding Pathophysiology 4th Ed. 2008

What are the two types of cellular division?
Source: http://www.accessexcellence.org
Source: Houston Biology Project: http://sites.google.com/site/houstonbiologyproject
Source: Indian River State College, http://faculty.irsc.edu/
Image Source: http://www.gilmerfreepress.net

What does the “universal genetic code” mean?

The “universal genetic code”
 All living organisms use precisely the same DNA
codes (codons – triplets of bases: A, C, T & G) to
specify the production of proteins.
 (Only exception being mitochondrial DNA)
Source: Huether, McCance Understanding Pathophysiology 4th Ed. 2008

Codons and AA
Source: University of Leicester: www.le.ac.uk
Source: University of Leicester: www.le.ac.uk
Source: University of Leicester: www.le.ac.uk
Source: http://artedi.ebc.uu.se/course/UGSBR/codonusage1.html
Source: University of Leicester: www.le.ac.uk

1) Transcription – from DNA to mRNA
 Waiter writes down the order from the customer (DNA)

2) Gene Splicing (introns and exons)
 HnRNA into “functional” mRNA via removal of introns,
thus only exons remain.

3) Translation – from mRNA to AA Chain
 The chef (ribosome) translates the order into the meal
Source: Huether, McCance Understanding Pathophysiology 4th Ed. 2008
Figure
2-5 (p. 40)

Source: Huether, McCance Understanding Pathophysiology 4th Ed. 2008

Mutations
 “Any inherited alteration of genetic material.”
 A massive diversity of Mutations exist:
▪ Polymorphisms
▪ Point Mutation
▪ Base pair substitution*
▪ Deletion
▪ Insertion
▪ Frameshift mutation*
▪ Inversion
*Focused on in text book
Source: Huether, McCance Understanding Pathophysiology 4th Ed. 2008

Mutations
▪ Polymorphisms – “many forms” = changing of genes
▪ Point Mutation = Base pair substitution – 1 base pair
replaces another
▪ Frameshift mutation – Insertion or deletion of base pairs
(as long as not a multiple of 3) causing a shift in the
“reading frame” thus causing a huge alteration in AA
sequence.
▪ Inversion – an entire section of DNA is reversed
Source: Huether, McCance Understanding Pathophysiology 4th Ed. 2008

Mutations
Point Mutation A point mutation is a simple change in
one base of the gene sequence. This is equivalent to
changing one letter in a sentence, such as this
example, where we change the 'c' in cat to an 'h':
Original
Point Mutation
The fat cat ate the wee rat.
The fat hat ate the wee rat.
Source: http://www.genetichealth.com

Mutations
Insertion Mutations that result in the addition of extra
DNA are called insertions. Insertions can also cause
frameshift mutations, and general result in a
nonfunctional protein.
Original
Insertion
The fat cat ate the wee rat.
The fat cat xlw ate the wee rat.
Source: http://www.genetichealth.com

Mutations
Deletion
Mutations that result in missing DNA are called
deletions. These can be small, such as the removal of
just one "word," or longer deletions that affect a large
number of genes on the chromosome. Deletions can
also cause frameshift mutations. In this example, the
deletion eliminated the word cat.
Original
Deletion
The fat cat ate the wee rat.
The fat ate the wee rat.
Source: http://www.genetichealth.com

Mutations
Insertion Mutations that result in the addition of
extra DNA are called insertions. Insertions can also
cause frameshift mutations, and general result in a
nonfunctional protein.
Original
Insertion
The fat cat ate the wee rat.
The fat cat xlw ate the wee rat.
Source: http://www.genetichealth.com

Mutations
Inversion In an inversion mutation, an entire section
of DNA is reversed. A small inversion may involve only
a few bases within a gene, while longer inversions
involve large regions of a chromosome containing
several genes.
Original
Insertion
The fat cat ate the wee rat.
The fat tar eew eht eta tac.
Source: http://www.genetichealth.com

Mutation
 Mutagens – agents that increase the frequency of
mutations.
▪ EX) radiation, nitrogen mustard, vinyl chloride, alkylating
agents, formaldehyde & sodium nitrite.
 Spontaneous mutations (mutation in absence of
mutagens) are very rare events.
Source: Huether, McCance Understanding Pathophysiology 4th Ed. 2008

Mutation
 Mutagens – agents that increase the frequency of
mutations.
▪ EX) radiation, nitrogen mustard, vinyl chloride, alkylating
agents, formaldehyde & sodium nitrite.
 Spontaneous mutations (mutation in absence of
mutagens) are very rare events.
Source: Huether, McCance Understanding Pathophysiology 4th Ed. 2008

Polyploidy
 Euploid Cells – cells with multiple of the normal number
of chromosomes (greek eu = good / true)
▪ Gametes Euploid = Haploid
▪ Somatic Cells = Diploid
▪ > Diploid = Polyploid
▪ Interestingly, some liver, bronchial and epithelial tissues are
physiologically polyploid.
▪ However a zygote that is triploidy or tetraploidy will spontaneously
abort, or rarely be stillborn. (Triploidy 1:10,000 births)
.
Source: Huether, McCance Understanding Pathophysiology 4th Ed. 2008

Aneuploidy
 A cell that does not contain a multiple of 23 chromo’s
▪ Trisomic / Trisomy = 3 copies of one chromosome
▪ Often survivable (13, 18, 21 / Trisomy 21 causes what disease? Trisomy 16 leading
cause of trisomy abortuses yet incombatable with life thus not seen in live births)
▪ Monosomy = the presence of only one copy of a given chromosome in
a diploid cell.
▪ Monosomy of ANY chromosome is lethal ( Generally “Loss of genetic material
induces a much greater consequence than duplication of genetic material”)
▪ Usually a consequence of nondisjunction during meiosis
(Text book says also in Mitosis – which is FALSE)
.
Source: Huether, McCance Understanding Pathophysiology 4th Ed. 2008

Aneuploidy
 Partial trisomy – an extra portion of a chromosome
is present in each cell. (Less severe consequences)
 Chromosomal Mosaics – the body has two or more
different cell lines (Thus different karyotypes in
different cells of the same organism / patient)
.
Source: Huether, McCance Understanding Pathophysiology 4th Ed. 2008

Examples of Aneuploidy (In Somatic Chromosomes)
 Trisomy 13 – Patau Syndrome
▪ One in 10,000 live births
 Trisomy 18 – Edwards Syndrome
▪ One in 3,000 live births (Increases with maternal age)
 Trisomy 21 – Down syndrome
▪ Women < 30 y/o risk of 1:1,000 = 0.1%
▪ Women > 35 y/o risk of 1:1,000 = 0.1%
▪ Women > 45 y/o risk of 3% - 5%
Source: Huether, McCance Understanding Pathophysiology 4th Ed. 2008

Trisomy 13 – Patau Syndrome
Some physical characteristics are
flattened facial features, malformed and
low-set ears, cleft lip and/or palate,
prominent heels, and genital
malformations. Often there are problems
with the nervous system, including
forebrain development, spinal cord
development, mental retardation, and
seizures. Vision and eye problems are
common, as well as respiratory and heart
defects. Approximately 45% of Patau
syndrome babies die within the first
month of life, while the number increases
to 70% in the first 6 months.
Source: Lucina Foundation: http://www.lucinafoundation.org

Trisomy 18 – Edward Syndrome
Patients with trisomy 18 can range
from mildly to severely affected.
Some characteristics of this
syndrome are clenched hands,
shield chest with short sternum,
short neck, and small jaw. Heart
defects are typical of trisomy 18,
including ventricular septal
defects, atrial septal defects, and
coarctation of the aorta. Also
common are omphaloceles
(externalized GI) and renal
pathology
Source: Lucina Foundation: http://www.lucinafoundation.org

Trisomy 21 – Down Syndrome
Down syndrome is a chromosomal
disorder which causes physical and
intellectual delays in development and
occurs when there are 3 chromosome
21's, resulting in 47 total chromosomes
instead of the normal 46. The most
common clinical features are short neck
and flat face, upward slanting eyes, low
muscle tone and a single crease across
the palm of the hand. Congenital heart
defects accompany Down syndrome in
about 40% of the cases. Vision and
hearing problems are also common.
Source: Lucina Foundation: http://www.lucinafoundation.org

Examples of Aneuploidy (In Sex Chromosomes)
 Trisomy X – Most Common Aneuploidies Effect 0.1% births
▪ Triplet of X in all cells. No physical abnormalities. Do have sterility, menstrual
irregularity and sometimes MR. (5 or > X increases MR, and introduction of physical
defects)
 Monosomy X – Turner Syndrome
▪ Results in a total of 45 chromosomes. (45,X)
▪ 15-20% of spontaneous abortions, only 0.5% survive to term. If survive, short
stature with pathoneumonic webbing of the neck, widely spaced nipples, reduced
carrying angle, Also aortic coactation is common, usually sterile but with no MR.
 Klinefelter Syndrome (47,XXy)
▪ Moderate MR, Have general male appearance but usually sterile, with
gynecomastia and incomplete secondary male maturation. Long limbs also
common. 1:1,000 male births, Increased freq q Materal age.
Source: Huether, McCance Understanding Pathophysiology 4th Ed. 2008

Mode of Inheritance – the pattern in which a genetic disease is
inherited through generations. Usually studied via pedigree charts.
 1) Autosomal Recessive
 2) Autosomal Dominant
 3) X – Linked Recessive
 4) X – Linked Dominant
.
Source: Huether, McCance Understanding Pathophysiology 4th Ed. 2008

Mode of Inheritance – the pattern in which a genetic disease is inherited
through generations. Usually studied via pedigree charts.
 1) Autosomal Recessive
▪ A genetic mutation (or allele) present on one of the 23 autosomes
▪ If one mutation then
- genotype = ?
- phenotype = ?
▪ If two mutations then
- genotype = ?
- phenotype = ?
 2) Autosomal Dominant
▪ A genetic mutation (or allele) present on one of the 23 autosomes
▪ If one mutation then
- genotype = ?
- phenotype = ?
▪ If two mutations then
- genotype = ?
- phenotype = ?
Source: Huether, McCance Understanding Pathophysiology 4th Ed. 2008

Mode of Inheritance – the pattern in which a genetic disease is
inherited through generations. Usually studied via pedigree charts.
 1) Autosomal Recessive
▪ A genetic mutation (or allele) present on one of the 23 autosomes
▪ If one mutation then the genotype would be rN – phenotype = normal + silent
“carrier”
▪ If two mutations then genotype would be rr – phenotype = presentation
 2) Autosomal Dominant
▪ A genetic mutation (or allele) present on one of the 23 autosomes
▪ If one mutation then genotype would be Dn – phenotype = presentation thus NO
“carrier”
▪ If two mutations then genotype would be DD – phenotype = presentation
Source: Huether, McCance Understanding Pathophysiology 4th Ed. 2008

Mode of Inheritance – the pattern in which a genetic disease is
inherited through generations. Usually studied via pedigree charts.
 3) X – Linked Recessive
▪
▪
▪
▪
A genetic mutation (or allele) present on the X chromosome
If Female + one mutation:
-genotype/ phenotype = ??
If Female + two mutations: -genotype/ phenotype = ??
If Male one mutation
-genotype/ phenotype = ??
 4) X – Linked Dominant
▪
▪
▪
▪
A genetic mutation (or allele) present on the X chromosome
If Female + one mutation:
-genotype/ phenotype = ??
If Female + two mutations: -genotype/ phenotype = ??
If Male one mutation
-genotype/ phenotype = ??
Source: Huether, McCance Understanding Pathophysiology 4th Ed. 2008

Mode of Inheritance – the pattern in which a genetic disease is
inherited through generations. Usually studied via pedigree charts.
 3) X – Linked Recessive
▪
▪
▪
▪
▪
A genetic mutation (or allele) present on the X chromosome
If Female + one mutation results in genotype Xx, phenotype “carrier.“
If Female + two mutations results in genotype xx, phenotype of disease
If Male one mutation = genotype xY + phenotype presentation
Male could not have two X chromosomal mutations
(unless what disease is present?)
 4) X – Linked Dominant
▪
▪
▪
▪
A genetic mutation (or allele) present on the X chromosome
If Female + one mutation results in genotype Xx, thus phenotype of disease
If Female + two mutations results in genotype XX, also phenotype of disease
If Male one mutation = genotype XY + phenotype presentation
Source: Huether, McCance Understanding Pathophysiology 4th Ed. 2008

Of Course, in reality it is much more complicated:
 Polygenic Traits
▪ Phenotypic traits that result from the genotype of multiple genes all acting
together to produce a complex cumulative effect.
 Multifactorial Inheritance
▪ When environmental factors influence the expression of the trait. Most traits are
multifactorial. The textbook sites height and IQ as more complicated phenotypes
that are determined and influenced by genotype and the infleuence of
environment as well.
 Empirical Risks
▪ Is the probability of disease not based on punnet squares and calculations but
instead is the probability of disease based on direct observation of patient samples
over time.
Source: Huether, McCance Understanding Pathophysiology 4th Ed. 2008
Source: http://www.answersingenesis.org
Source: http://www.answersingenesis.org
Source: http://googleimages.com
Image Source: http://www.gilmerfreepress.net

Review of Terms:






Atrophy
Hypertrophy
Hyperplasia
Metaplasia
Dysplasia
Hypoxia
▪ Which of these above are physiologic vs pathologic??
Source: Huether, McCance Understanding Pathophysiology 4th Ed. 2008
Source: Cervical Cancer Study by http://www.colposcopy.org.uk
Source: Cervical Cancer Study by http://www.colposcopy.org.uk
Source: Fetal and Neonatal Journal - http://fn.bmj.com
Source: http://basicpathology-histopathology.com

Table 3-1:
 Adaptation – atrophy, hypertrophy, hyperplasia & metaplasia
 Active Cell Injury – Immediate response of the entire cell.
▪ a) Reversible – Loss of ATP, cellular swelling, detachment of ribosomes,
autophagy of lysosomes.
▪ b) Irreversible – “Point of no return” structurally when severe vacuolization
of the mitochondria occurs and calcium moves into the cell.
▪ c) Necrosis – common type of cells death with severe cell swelling and
breakdown of roganelles
 Apoptosis – “Programmed Cell Death” physiologic cellular self
destruction for elimination of unwanted cell populations.
When there is a problem or lack of apoptosis what disease
develops?
Source: Huether, McCance Understanding Pathophysiology 4th Ed. 2008

Table 3-1: …continued…
 Chronic cell injury – subcellular alterations
▪ Persistent stimuli response may involve only specific organelles or
cytoskeleton (ex-phagocytosis of bacteria)
 Accumulations or Infiltrations
▪ Water, pigments, lipids, glycogen, proteins
 Pathologic Calcification
▪ Dystrophic and metastatic calcification
.
Source: Huether, McCance Understanding Pathophysiology 4th Ed. 2008

Apoptosis: is the active process of “programmed cell death”
 An average adult will produce 10 BILLION new cells – and also kill off 10
billion cells, to be recycled and renewed.
 Apoptosis – Occurs from embryologic development through old age, to
regulate and provide physiologic homeostasis.
▪ Physiologic Apoptosis  Responsible for local deletion of cells during tissue
turnover and normalembryonic development. Also seen in normal endocrine
regulated atrophy.
▪ Pathologic Apoptosis  is the result of intracellular events or adverse exogenous
stimuli.
Examples:
▪ Viral Hepatitis C will cause massive portions of the liver to undergo apoptosis.
▪ Apoptosis in hemopoietic cells is linked to the production of free radicals and can spontaneously
occur in some malignant turmors as well as what occurs id cells that undergo ionizing radiation
and chemotherapy
Source: Huether, McCance Understanding Pathophysiology 4th Ed. 2008
Source: http://www.microbiologybytes.com

Apoptosis: is the active process of “programmed cell death”
Source: http://ghr.nlm.nih.gov

Absence of apoptosis will cause serious pathologic change.
 A mutation in a gene (Example bcl-2) that promotes apoptosis, will
then allow the cell to proliferate uncontrollably = cancer.
 Know the difference between: (Muy importante mis amigos…)
▪ Tumor suppressor genes
▪ Onchogenes
 Apoptosis – is often performed from initial signal to termination of
a cell in only a few minutes. Thus it can be difficult to quantify or
visualize rate of apoptosis occurring.
▪ Karyohexis = fragmentation and destruction of the nucleus
▪ Karyohexis is the primary marker for apoptosis
Source: Huether, McCance Understanding Pathophysiology 4th Ed. 2008
Image Source: http://www.gilmerfreepress.net
Day 2 of Patho will focus on Oncology
CH 9 – Biology of Cancer and Tumor Spread
CH 10 – Cancer Epidemiology, Manifestations & TX
Lets start with our baseline knowledge…
What do you know about cancer?
Who does it primarily effect?
Why?
Critical Terminology:
1) Tumor
2) Neoplasm
3) Benign
4) Malignant
5) Metastasis
Critical Terminology: Definitions from Huether, Understanding Patho.
1) Tumor – originally defined swelling now refers to new growth
2) Neoplasm – new growth
3) Benign – usually well encapsulated and well differentiated, retain
some normal tissue structure and do not invade or spread to
distant locations.
4) Malignant – rapid growth rates and specific microscopic
alterations, including loss of differentiation; absence of normal
tissue organization; lack of capsule; invasion into blood vessels,
lymphatics, and surrounding structures; and distant spread.
5) Metastasis – distant spread of malignant tumor
Critical Terminology: Definitions from Robin’s, Patho of Basic Disease.
1) Tumor – new growth of tissue from genetic changes that allow
excessive and unregulated proliferation thus becoming autonomous.
2) Neoplasm – is an abnormal mass of tissue, the growth of which
exceeds and is uncoordinated with that of the normal tissues and persists in
the same excessive manner after cessation of the stimuli which evoked the
change
3) Benign – microscopic and gross characteristics are considered
“relatively innocent,” implying that it will remain localized, is generally
amenable to local surgical removal, and patients generally survive.
4) Malignant – implies that the lesion can invade and destroy adjacent
structures and spread to distant sites (metastasis) and cause death.
Pathologically all tumors have two basic components:
1) Parenchyma – constituted from the clonal neoplastic cells
2) Stroma – the reactive supporting tissue for the parenchyma
(CT, vasculature, and variable macrophages and lymphocytes)
Source: Robins Pathologic Basis of Disease 8th Ed. 2010
Benign Tumors – designated with suffix – oma
examples:
fibroma
chondroma
meningioma
lipoma
Note – nomenclature for benign epithelial tumors is more
complicated
Malignant Tumors
From Germ layer Origin  are called carcinomas
ex) Squamous cell carcinoma, adenocarcinoma
From Mesenchymal tissue  are called sarcomas
ex) fibrosarchoma,
chondrosarchoma, rhabdomyosarcoma
th
Source: Robins Pathologic Basis of Disease 8 Ed. 2010
Malignant Tumors
A majority of the time it is clear that benign and malignant neoplasms
within the parenchymal cells were derived from a single cell and thus bear a
close resemblance to each other.
Important exceptions:
1) Mixed Tumors
2) Teratomas
Source: Robins Pathologic Basis of Disease 8th Ed. 2010
Malignant Tumors
Important exceptions:
1) Mixed Tumors – divergent differentiation of a single neoplastic clone
along two lineages will create a “Pleomorphic adenoma”
2) Teratomas – neoplasm containing recognizable mature or immature cells
/ tissues representative of more than one germ cell layer and sometimes all
three. Origination from totipotential cells (usually ovarian or testicular), yet
sometimes present from “embryonic rests.” Teratomas have the capacity to
differentiate into any of the cell types found in the adult body. Benign and
Malignant teratomas exist based on differentiation.
Source: Robins Pathologic Basis of Disease 8th Ed. 2010
Source: Huether, McCance Understanding Pathophysiology 4th Ed. 2008
Source: Huether, McCance Understanding Pathophysiology 4th Ed. 2008
A = Asymmetry
Normal moles or freckles are completely symmetrical. If you were to draw a line
through a normal spot, you would have two symmetrical halves. In cases of skin
cancer, spots will not look the same on both sides.
B = Boarder
A mole or spot with blurry and/or jagged edges.
C = Color
A mole that is more than one hue is suspicious and needs to be evaluated by a
doctor. Normal spots are usually one color. This can include lightening or darkening
of the mole.
D = Diameter
If it is larger than a pencil eraser (~1/4in or 6mm), it needs to be examined by a
doctor. This includes areas that do not have other abnormalities.
E = Elevation
If mole is raised above the surface of the skin or if it has an uneven surface.
Source: Huether, McCance Understanding Pathophysiology 4th Ed. 2008
What is the most important parameter of all
oncology screening???
What is the most important parameter of all
oncology screening.
 Relative Change within a single patient
Source: Huether, McCance Understanding Pathophysiology 4th Ed. 2008
Source: Huether, McCance Understanding Pathophysiology 4th Ed. 2008
Oncogenes
“Are mutant genes that in their normal nonmutant
state direct synthesis of proteins that positively
regulate (accelerate) proliferation.”
Tumor-Supressor Genes
“Encode proteins that in their normal state
negatively regulate (put the brakes on) proliferation.”
Oncogenes
ex) MYC protooncogene on chromo 8
Normally turned on in proliferating lymphocytes
and turned off in mature lymphocytes.
Translocation of myc t(8;14) Ig gene has high levels
of translation in mature lymphoctes, thus the Ig
promotor is now regulates and increases myc
production, thus causing Burkitt lymphoma.
(N-myc – gene detected in human neuroblastoma cells)
Tumor-Supressor Genes
ex) Retinoblastoma (Rb) gene, normally strongly
inhibits the cell division cycle. When it is inactivated,
the cell division cycle can proceed unchecked. Rb is
mutated in retinoblastoma (obviously) but also in
many lung, breast and bone cancers.
p53 = The “Guardian of the Human Genome”
The p53 protein is a tumor suppressor encoded by a
gene whose disruption is associated with
approximately 50 to 55 percent of human cancers. The
p53 protein acts as a checkpoint in the cell cycle, either
preventing or initiating programmed cell death. Since
cancer is the unchecked proliferation of cells, p53's role
is critical
p53 = The “Guardian of the Human Genome”
The p53 molecule can be inactivated in several ways. In
some human families, for example, p53 mutations are
inherited, and family members have a high incidence
of cancer. More often, the molecule is inactivated by
an outside source. DNA tumor viruses, such as the
human adenovirus and the human papilloma virus, can
bind to and inactivate the p53 protein function,
altering cells and initiating tumor growth. In addition,
some sarcomas amplify another gene, called mdm-2,
which produces a protein that binds to p53 and
inactivates it, much the way the DNA tumor viruses do.
Source: Huether, McCance Understanding Pathophysiology 4th Ed. 2008
Source: Genentech Bio-oncology http://www.biooncology.com

NRP1 is a growth factor receptor that is important for promoting
vascular growth and maturation. Anti-NRP1 is a monoclonal
antibody designed to target NRP1 and inhibit angiogenesis and the
subsequent vascular maturation that is necessary to form the
functional vasculature that supports tumor growth
Source: Genentech Bio-oncology http://www.biooncology.com
Net decrease in vascular
maturation and vessel
sprouting with combination TX
of Anti-VEGF, Anti-NRP1, AntiEGFL7
Source: Genentech Bio-oncology http://www.biooncology.com
Another mechanisms of
oncogenesis is the
permanent activation of
telomerase which inhibits
natural cell death via
programed loss of the
telomere in each mitotic
division. (Fig 9.11)
Source: Huether, McCance Understanding Pathophysiology 4th Ed. 2008
CH 10 – Cancer Epidemiology, Manifestations & TX
Source: Huether, McCance Understanding Pathophysiology 4th Ed. 2008
Source: Huether, McCance Understanding Pathophysiology 4th Ed. 2008
Females
26% - Breast
14% - Lung
10% - Colon & Rectum
6% - Uterine
4% - Melanoma of Skin
4% - Thyroid
23% - Other
Males
25% - Prostate
15% - Lung
10% - Colon & Rectum
7% - Urinary & Bladder
5% - Non-Hodgkin lymphoma
5% - Melanoma of skin
20% - Other
Source: Cancer Statistics, 2008. CA Cancer Journal Clinical Medicine 58:2, 2008
Females
26% - Lung
15% - Breast
9% - Colon & Rectum
6% - Pancreatic
6% - Ovarian
3% - Leukemia
2% - Brain
25% - Other
Males
31% - Lung
10% - Prostate
8% - Colon & Rectum
6% - Pancreatic
4% - Esophageal
4% - Liver
4% - Leukemia
24% - Other
Source: Cancer Statistics, 2008. CA Cancer Journal Clinical Medicine 58:2, 2008
Female Incidence
26% - Breast
14% - Lung
10% - Colon & Rectum
6% - Uterine
4% - Melanoma of Skin
4% - Thyroid
23% - Other
Female Death
26% - Lung
15% - Breast
9% - Colon & Rectum
6% - Pancreatic
6% - Ovarian
3% - Leukemia
25% - Other
Source: Cancer Statistics, 2008. CA Cancer Journal Clinical Medicine 58:2, 2008
Male Incidence
25% - Prostate
15% - Lung
9% - Colon & Rectum
7% - Urinary & Bladder
5% - Non-Hodgkin lymphoma
5% - Melanoma of skin
4% - Kidney
25% - Other
Males Deaths
31% - Lung
10% - Prostate
8% - Colon & Rectum
6% - Pancreatic
4% - Esophageal
4% - Liver
4% - Leukemia
24% - Other
Source: Cancer Statistics, 2008. CA Cancer Journal Clinical Medicine 58:2, 2008
Mutations or chromosomal
aberrations are shown as filled
circles and apparently normal
cells as open circles.
A, If a cell faithfully repairs DNA
damage, then its clonal
descendents will appear normal.
B, If a cell is directly mutated by
radiation, then all its
descendents will express the
same mutation.
Source: Huether, McCance Understanding Pathophysiology 4th Ed. 2008
C, Radiation-induced
genomic instability is
characterized by nonclonal
effects in descendant cells.
Source: Huether, McCance Understanding Pathophysiology 4th Ed. 2008
Primary CA TX options:
1) Chemotherapy – Chemical destruction of cellular proliferation (8 major types)
2) Radiation Therapy (In 2009 1.47 Million Americans were diagnosed with CA and
60-75% received radiation therapy)
a. Proton Therapy
b. Brachytherapy (Internal Radiation Therapy)
3) Surgery
a. Excision
b. Cryosurgery
4) Immunotherapy (Hematopoietic GF, INF’s, IL’s, Mono’s, Ovarian CA Vac)
5) Angiogenesis Inhibitors
6) Bone Marrow Transplantation
7) Gene Therapy
8) Laser Treatments
a. Gama Radiation
b. Photodynamic Therapy
c. Hyperthermia (Tissue destroyed via raising temp to 113F)
Source: National Cancer Institute http://www.cancer.gov
Vaccine for Ovarian CA:
1) In 2008, Dr. Sybilann Williams, a gynecologic oncologist and surgeon of CTCA,
began a research study with Dr. David Berd of National Director of
Immunotherapy, to develop and evaluate the efficacy of personalized ovarian
cancer vaccines for women with Chemo Resistant, advanced-stage disease.
2) First exploratory surgery is performed (sometimes called “debulking surgery”)
during which a cancerous tissue sample is obtained then a patient specific
“vaccine” is created to develop and then delivery antibodies against the individual
tissue specific ovarian CA.
3) Chemotherapy is halted and vaccine is delivered via IM injection over 8 week
period of time during which the patient is closely monitored via PE, CT, and blood
work for any progression of the CA, which if is detected the vaccine is DCed and
Chemo is resumed.
Source: National Cancer Institute http://www.cancer.gov
Chemotherapy:
1) Chemoembolization - Chemoembolization allows high doses of chemotherapy drugs
to be targeted directly to the cancerous tissue for a longer period of time, without
exposing the entire body to the effect of the drugs.
*Primarily for Hepatic tx.
Secondarily: Prostate, Breast, Colorectal
1) Chronotherapy - drug-specific research to track a variety of symptoms and discover
when tumor tissues may be most sensitive to the chemotherapy drugs. Time sensitive
delivery based on specific patient and CA type.
* No specified type of CA
2) HIPEC – Hyperthermic Intraperitoneal Chemo, surgical oncologist removes as much
cancerous tissue as possible, then a chemotherapy solution circulates through the
abdomen for approximately 90 minutes.
* Colorectal or Ovarian CA
3) IAC – Intra-Arterial Chemo, angiogram guided percutaneous delivery of Chemo.
* Hepatic or Pancreatic CA
Source: Cancer Treatment Centers of America http://www.cancercenter.com
Chemotherapy:
5) Intraperitoneal Chemo - directly targets cancer cells in the abdomen, minimizing drug
exposure to healthy tissues.
*Primarily for Ovarian CA
6) Intrathecal Chemo – spinal tap, or intracranial delievery of tx directly into the CSF
* CA of the CNS, Leukemis, or lymphoma
7) Intratumoral Chemo – delivery of tx into the lung tissue
*Non small cell lung CA
8) Metronomic Chemo – designed for patients that cannot tolerate full dose chemo, thus
they receive titrated partial dose treatments.
*Not CA type specific
Source: Cancer Treatment Centers of America http://www.cancercenter.com
Source: Huether, McCance Understanding Pathophysiology 4th Ed. 2008
… of Pathopysiology!!
Remember to…
KEEP UP WITH YOUR:
1) Text READING
2) Powerpoint Review
3) Study Guide / Evolve Prep