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Surviving Chemotherapy
Consequences of Systemic Cancer Treatment
to Normal Cells, Tissues, & Organs
BIOL 505, Problems in Biological Instruction
Topics in Anatomy & Physiology
A Learning Module for Problems Encountered in the
Treatment of Cancer
Margaret McMichael, Ph.D., CLSp[MB]
Content & Objectives
• Identify characteristics unique to cancer cells.
• List and describe the stages of carcinogenesis.
• Define and explain the purpose of chemotherapy
in the treatment of cancer.
• Classify chemotherapy drugs according to their
modes of action. Describe how drugs in each
class alter the ability of cancer cells to grow
and/or replicate. Give an example of commonly
used drugs in each class.
• Explain why chemotherapy drugs alter the
functions of normal cells.
Content & Objectives
• Identify risk factors for cancer, and
distinguish between those that can be
modified and those that cannot.
• Describe the relationship between diet and
cancer risk. Identify the purpose of the
Dietary Guidelines for Americans and
MyPyramid.
• Define antioxidant, give examples of
antioxidants, and describe why they are
important components of a healthful diet.
Content & Objectives
• Describe the the probability of reversing or
‘curing’ a disease such as cancer by dietary
means.
• Describe the rationale for examining the
palliative use of antioxidant supplements to
treat the consequences of chemotherapy to
normal cells.
• Explain the current recommendations for the
use of dietary antioxidant supplements during
treatment of cancer patients with chemotherapy.
Surviving Chemotherapy:
Presentation Overview
• What is Cancer?
• What is Chemotherapy?
• Consequences of Chemotherapy to
Healthy Cells & Organs
• Nutrition & Cancer Risk
• Nutrition & Cancer Treatment
What Is Cancer?
What is Cancer?
Over 100 different diseases with common characteristics
• cells in a part of the body begin to grow out of
control
• cancer cells develop because of damage to DNA that
is not repaired: normal cells repair DNA or die
• cancers can begin in many different parts of the body
• different types of cancer can act very differently

cells grow at different rates & respond to different
treatments
Review: The Cell Cycle
• = time between divisions of a cell
• stem or progenitor cells go through the cell
cycle many times

found in the skin, bones, testes, for example
• some specialized cells no longer enter the
cell cycle (e.g., neurons and muscle cells)
The Cell Cycle
• Interphase
• Mitosis
Mader (2006) Copyright © The McGraw Hill Companies.
Used with permission.
The Stages of Interphase
• G1: protein synthesis & assembly occurs
• S: DNA replicates (S = synthesis!)
• G2: changes in the cytoskeleton occur
metabolic preparations for mitosis
 synthesis of proteins found in microtubules that
will assist in cell division

Phases of Mitosis
•
•
•
•
Prophase
Metaphase
Anaphase
Telophase
The Mitotic Spindle
Mader (2006) Copyright ©The McGraw-Hill Companies. Used with permission.
Control of the Cell Cycle
• external signals (growth factors) received at
the plasma membrane cause cells to
undergo the cell cycle repeatedly
• internal signal (cyclin) stimulates cells to
finish the cell cycle
• DNA damage stops the cell cycle in the G1
stage
• p53 protein initiates apoptosis (programmed
cell death)
Control of the Cell Cycle
The cell
cycle is
normally
regulated at
‘checkpoints’
(traffic lights)
by
stimulatory
and
inhibitory
growth
factors.
G2  M
checkpoint
M  G1
checkpoint
G1
checkpoint
Copyright © The McGraw-Hill
Companies. Used with permission.
Apoptosis
Mader (2006) Copyright The McGraw-Hill Companies. Used with permission.
What Causes Cancer?
• exact cause of cancer remains a mystery
• in general
anything that damages DNA (= mutagenic)
 anything that stimulates the rate of mitosis
(cells are most susceptible to mutations during
S phase when DNA is being replicated)

ACS 2008
Characteristics Common to
Cancer Cells
Unlike normal cells, cancer cells
•
•
•
•
•
•
•
lack differentiation
have abnormal nuclei
have unlimited potential to replicate
form tumors
have no need for growth factors
gradually become abnormal
undergo angiogenesis and metastasis
(Mader 2006)
Hallmarks of Cancer
• cells go through the cell cycle independent
of growth factors
• cells no longer respond to cell cycle
inhibitory signals
• cells fail to to through apoptosis when they
should (e.g., when DNA is damaged)
• cells go through the cell cycle indefinitely
(= become immortal)
Cancer Cells Gradually Become Abnormal:
carcinogenesis = development of cancer
• initiation: single cell mutation
converting a proto-oncogene to an oncogen
 inactivation of a tumor-suppressor gene

• promotion: division and continued
mutation
• progression: eventually a mutated cell has
the ability to invade surrounding tissues
Initiation: a series of mutations transform
a normal cell into a malignant cell
Normal cell
First mutation
Second mutation
Third mutation
Malignant cell
resulting from
further mutation
How Does Initiation Occur?
• proto-oncongenes become oncogenes
• what are proto-oncogenes?

genes that code for proteins that promote the cell
cycle & prevent apoptosis



often likened to the gas pedal of a car, causing
acceleration into the cell cycle (Mader 2006)
cylcins are such proteins, promoting progression through
the cell cycle
example: cyclin E, an S-phase cyclin, is found in
elevated levels (= gene is over-expressed) in women with
breast cancer that does not respond treatment (ACS 2008)
How Does Initiation Occur?
• proto-oncogenes become oncogenes
mutations allow cells to go through the cell cycle
unlimited times (no red lights); cell death is
inhibited
 mutations are inherited by all of the cancer cells

(Mader 2006)
How Does Initiation Occur?
• inactivation of a tumor-suppressor gene
• what is a tumor-suppressor gene?
gene that codes for a protein that inhibits the cell
cycle and promote apoptosis
 often likened to the brakes of a car because it
inhibits acceleration (Mader 2006)
 mutations in tumor-suppressor genes result in the
loss of the ability of cells to inhibit the cell cycle
or stimulate apoptosis



no inhibitors of cyclin; no promotion of the sequence
of events that lead to cell death
mutations are inherited by all of the cancer cells
HANAHAN & WEINBERG
CELL 2000
CANCER IS CAUSED BY THE BREAKDOWN OF SEVERAL
IMPORTANT NETWORKS THAT GUARD AGAINST UNCONTROLLED
CELL DIVISION (= breakdown of control of the cell cycle)
HANAHAN & WEINBERG
CELL 2000
CANCER IS CAUSED BY THE BREAKDOWN OF SEVERAL
IMPORTANT NETWORKS THAT GUARD AGAINST UNCONTROLLED
CELL DIVISION (= breakdown of control of the cell cycle)
Shier et al. 2004. Copyright The McGraw-Hill Companies. Used with permission.
Shier et al. 2004. Copyright The McGraw-Hill Companies. Used with permission.
Shier et al. 2004. Copyright The McGraw-Hill Companies. Used with permission.
Example:
Cervical Dysplasia and Cancer:
How Is Cancer Treated?
An Introduction to Chemotherapy
What is Chemotherapy?
• ACS: medicines used to treat cancer

antineoplastic agents = prevent or inhibit new
growth
• systemic treatment (surgery & radiation are localized
treatments)
many different forms
 interfere with mechanisms of cell cycle to induce
apoptosis
 neoadjuvant therapy (before surgery or radiation);
adjuvant therapy (after surgery or radiation)

What is Chemotherapy?
• most traditional chemotherapy drugs interfere
with the synthesis of DNA and /or RNA,
causing apoptosis or the end of cell replication
• others interfere with the formation or action of
the mitotic spindle, composed of microtubules
Why is Chemotherapy Administered?
• goals for chemotherapy treatment:
‘curative’ intent – tumor or cancer disappears
and does not return (drs. do not use this term)
 control – limit growth of tumors & growth and
spread of cancer cells throughout the body
 palliation – improve the quality of life when
cancer is at an advanced stage

ACS 2008
Commonly Used Chemotherapy Drugs
• grouped according to how they work,
chemical structure, origin (many are derived
from plants!)
• knowing how they work is especially
important for
planning treatment sequence, dosing (dr’s
responsibility)
 anticipating side effects (consequences to
healthy cells)

Commonly Used Chemotherapy Drugs
• alkylating agents – directly damage DNA to
prevent cancer cells from reproducing
• anti-metabolites – interfere with DNA and RNA
by substituting for normal building blocks
• anti-tumor antibiotics – interfere with enzymes
needed for DNA replication
• mitotic inhibitors – stop mitosis or inhibit
enzymes needed to make proteins involved in cell
reproduction
(ACS 2008; Mader 2006)
Alkylating Agents
• interfere with growth of cancer cells by
blocking DNA replication

also cause base substitutions, cross-linking, and
single-strand breaks
• work in all phases of the cell cycle
• used in treatment of leukemia, lymphoma,
Hodgkin disease, multiple myeloma;
cancers of lungs, breast, & ovary as well
(ACS 2008; Mader 2006; Rock & DeMichele 2003)
Alkylating Agents
• examples:
cyclophosphamide (Cytoxan®)
 nitrosureas (streptozocin)
 platinum compounds (cisplatin, carboplatin,
oxalaplatin)

• consequences to normal cells:
premature ovarian failure, bone loss, leukemia
 peripheral neuropathy (platinum
compounds,esp.)

(ACS 2008; Rock & DeMichele 2003; Windebank & Grisold 2008)
Anti-metabolites
• structurally and functionally similar to
natural compounds involved in RNA &
DNA synthesis; incorporation into DNA
leads to cell death
• act during S of interphase
• commonly used to treat leukemias; tumors
of breast, ovary, & intestinal tract
(ACS 2008; Rock & DeMichele 2003)
Anti-metabolites
• examples:

5-fluorouracil (5-FU), capecitabine, methotrexate
• consequences to normal cells:
premature ovarian failure
 hand-foot syndrome (severe swelling of the
hands & feet, even peeling of the skin in one or
both places)

(ACS 2008; Rock & DeMichele 2003)
Anti-tumor Antibiotics
• not the kind of antibiotics used to treat infections!
• work by a number of mechanisms:




intercalation into DNA
inhibition of DNA-dependent RNA polymerase
generate oxygen free-radicals leading to DNA strand
breaks
change cell membranes
• work in all phases of the cell cycle
• used to treat a variety of cancers
(ACS 2008; Mader 2006; Rock & DeMichele 2003)
Anti-tumor Antibiotics
• examples:
anthracyclines (doxorubicin)
 actinomycin-D

• consequences to normal cells:
cardiomyopathy
 premature ovarian failure
 secondary malignancies

(ACS 2008; Rock & DeMichele 2003)
Mitotic Inhibitors
• stop mitosis or inhibit certain enzymes from
making proteins needed for cell
reproduction
• primarily work during mitosis (M of cell
cycle) but can damage cells in all phases

stabilize microtubules, lead to arrested mitosis
• used to treat many different types of cancer,
including breast, lung, myelomas,
lymphomas, and leukemias
(ACS 2008; Mader 2006; Rock & DeMichele 2003)
Mitotic Inhibitors
• examples:
taxanes (paclitaxel, docetaxel)
 vinca alkaloids (vincristine, vinblastine)

• consequences to normal cells:
premature ovarian failure
 peripheral neuropathy – some drugs cause
sensory neuropathy, others cause motor
neuropathy

(ACS 2008; Rock & DeMichele 2003; Windebank & Grisold 2008)
Administration of Chemotherapy
• high-doses
 may be limited by toxicity towards normal cells
 usually administered in cyclic regimens – repeated
administrations at intervals for regeneration of normal cells
(e.g., bone marrow)
 routes: oral, topical, subcutaneous, intramuscular; directly
into vessels (intravenous, intra-arterial), cavities (pleural,
peritoneal), tumor (intratumoral), intrathecal (into
cerebrospinal fluid)
• combination of several drugs with different
mechanisms of action, different resistance mechanisms,
different dose-limiting toxicities
How Selective Are Chemotherapy Drugs?
• many normal cells regularly divide, which
requires cycles of DNA replication & RNA
synthesis and normal structure & function of
microtubules
• chemotherapy drugs are toxic to normal
dividing cells, particularly those that divide
rapidly and often:

in bone marrow, the stomach & intestines, gonads,
integument (skin, hair follicles, nails)
Consequences of Chemotherapy
to Normal Cells
A Description of What Can Happen to
the Functions of Organ Systems During
Cancer Treatment with Chemotherapy
Copyright © The McGraw-Hill Companies, Inc. Used with permission.
Consequences of Chemotherapy to
Normal Components of the Skeletal
System: Hemopoietic Stem Cells
• mitosis is inhibited
 leukopenia/neutropenia
increase risk
for infection
o

can limit dose or schedule of
chemotherapy
Leukine®, Neupogen®, Neulasta®
 anemia:
fatigue, shortness of breath
low Hb &/or hematocrit
Aranesp®, Procrit®
o
 thrombocytopenia:
bruise easily,
nose bleeds, minor cuts bleed longer
than usual
Neumega®
Copyright © The McGraw-Hill Companies, Inc. Used with permission
Consequences of Chemotherapy
to Normal Components of the
Skeletal System: Bone Loss
“Breast cancer survivors,
particularly those receiving adjuvant
chemotherapy, are at risk of
developing defects in bone
mineralization; these effects may be
modulated by the development of
treatment-induced menopause.”
(Rock & DeMichele, 2003)
Copyright © The McGraw-Hill Companies, Inc. Used with permission
Consequences of Chemotherapy
to Normal Components of the
Central Nervous System
‘Chemo Brain is Real, Cause is Unknown’

mental cloudiness resulting from
chemotherapy
• recent imaging studies: after
chemotherapy, some pts have smaller
brain size in regions that deal with
memory, planning, verbal expression,
monitoring thought processes &
behavior, and inhibition
• brain is protected by the blood brain
barrier; entry of drugs limited by size,
lipid solubility
Blood Supply & the
Brain Barrier System
• blood-brain barrier = endothelium
NS Review
 permeable to lipid-soluble materials
• alcohol, O2, CO2, nicotine and anesthetics
 circumventricular organs
• in 3rd & 4th ventricles
• barrier system absent, where blood has direct access to
brain
• allows brain to monitor glucose, pH, osmolarity and
others
• route for HIV virus to invade the brain
• blood-CSF barrier at choroid plexus: ependymal
cells joined by tight junctions
Continuous Capillary
Activity 5
Copyright © The McGraw-Hill Companies, Inc. Used with permission
Copyright © The McGraw-Hill Companies, Inc. Used with permission
Consequences of Chemotherapy
to Normal Components of the
Peripheral Nervous System: ANS
• problems are relatively rare; most
common are
 nausea
 constipation
 sexual dysfunction
 urinary retention
 blood pressure alterations
Copyright © The McGraw-Hill Companies, Inc. Used with permission
Consequences of Chemotherapy
to Normal Components of the
Peripheral Nervous System
Chemotherapy-Induced Peripheral
Neuropathy; CIPN or CPN


sensory: tingling, numbness, decreased
sensation, pain
motor: weakness, problems walking,
clumsiness, loss of balance, diminished fine
motor skills (e.g., writing, buttoning
clothing)
• neurotoxicity can limit dose and/or alter
schedule for treatment
• drugs enter peripheral nerves through
fenestrated capillaries
General Anatomy of
Nerves & Ganglia
NS Review
• nerve = bundle of nerve
Copyright © The McGraw-Hill Companies, Inc. Used with permission
fibers (axons)
• epineurium covers
nerves
• perineurium surrounds a
fascicle
• endoneurium covers &
separates individual
nerve fibers
• blood vessels in epineurium & perineurium branch into
capillaries of endoneurium, supplying oxygen & nutrients to
neurons
General Anatomy of
Nerves & Ganglia
• ganglion = cluster
of neuron cell
bodies in PNS
• dorsal root
ganglion contains
sensory neuron cell
bodies

supplied by
capillaries with
fenestrations
NS Review
Copyright © The McGraw-Hill Companies, Inc. Used with permission
Fenestrated Capillary
Activity 6
Copyright © The McGraw-Hill Companies, Inc. Used with permission
WAIT!
Neurons are not rapidly dividing cells –
how does chemo hurt them??
Chemotherapy-induced peripheral
neuropathy
• second in frequency to hematological
toxicities in chemotherapy patients
• “Unlike hematological side effects that can
be treated with hemtopoietic growth factors,
neuropathies cannot be treated and
protective treatment strategies have not
been effective.”
(Windebank & Grisold 2008)
Why are chemotherapeutic agents toxic
to cells of PNS?
• neurons have programmed cell death
pathways that are particularly sensitive to
DNA damage induced by many
chemotherapeutic agents
(Windebank & Grisold 2008)
Why are chemotherapeutic agents toxic
to cells of PNS?
• ‘primary sensory neurons are contained in
ganglia that lie outside the blood-brain
barrier and are supplied by fenestrated
capillaries that allow free passage of
molecules between the bloodstream &
interstitial fluid in the ganglia’

chemotherapeutic agents can enter the ganglia
and thus the sensory neurons
(Windebank & Grisold 2008)
Why are chemotherapeutic agents toxic
to cells of PNS?
• ‘long peripheral nerve axons are susceptible
to any agents that interfere with the energy
metabolism of axonal transport’
chemotherapeutic agents that target the
increased mitochondrial activity of cancer cells
may impair axonal transport and thus contribute
to peripheral neuropathy
 energy metabolism is impaired by
chemotherapy-induced anemia, for example

(Windebank & Grisold 2008)
Why are chemotherapeutic agents toxic
to cells of PNS?
• ‘long peripheral nerve axons are susceptible
to any agents that interfere with the
microtubule-based axonal transport’

chemotherapeutic agents that interfere with
microtubule structure and function include the
platinum compounds, vinca alkaloids, and
taxanes; these drugs are commonly associated
with peripheral neuropathy
(Windebank & Grisold 2008)
What is so important about axonal
transport?
= two-way transport of molecules & materials
(proteins, organelles) along an axon
 anterograde
(from soma to axon): employs kinesin to
transport substances needed for axolemma repair, for
gated ion channel proteins, as enzymes or
neurotransmitters
 retrograde (from axon to soma): employs protein called
dynein to transport molecules for disposal or recycling
 microtubules are the road or track, kinesin & dynein are
the transport vehicles
How do you transport molecules along axons
when the road is gone??
(Saladin 2007)
Commonly Used Chemotherapy Drugs
and Evidence of CIPN
Drug
platinum
compounds
taxanes
vinca
alkaloids
Sensory
Motor
Reflexes
10-80% of pts1;
feet & hands;
pain common
normal
reduced in
proportion to
sensory loss
10-20% of pts;
primarily in feet
uncommon;
mild weakness
in foot muscles
reduced ankle
reflexes
30-40% of pts;
primarily in
lower limbs
5-10% of pts;
weakness in
lower limbs,
progressing to
foot drop2
early reduction
or absence
1 lowest with carboplatin, highest with oxaliplatin
2 interruption of nerve-muscle communication results in the foot dragging while walking
(condensed from Windebank & Grisold 2008)
Why are platinum compounds toxic to
cells of the PNS?
• usually dependent on cumulative dose
• produce ganglionopathy; drugs enter dorsal root
ganglia (where sensory nerves enter spinal cord)
through fenestrated capillaries

bind to DNA in neurons, induce re-entry into cell cycle
and apoptosis
• sensory loss (= paresthesia) may progress for
several months after treatment ends: this is called
‘coasting’ and is unique to platinum compounds
(Rock and DeMichele 2003; Windebank & Grisold 2008)
Why are vinca alkaloids toxic to cells of
the PNS?
• inhibit assembly and promote disassembly of
microtubules, which inhibits axonal transport
• axonal damage is length-dependent: the farther way a
structure is, the greater the neuropathy

sensory & motor functions impaired in lower limbs first,
then in upper limbs
• symptoms appear in first 3 months of treatment;
sensory (paresthesia, pain) as well as motor (muscle
cramps)
• soma is spared; recovery of function usually good
(Rock and DeMichele 2003; Windebank & Grisold 2008)
Why are taxanes toxic to cells of the
PNS?
• hyperstabilize microtubules of spindle leading to
cell cycle arrest
• likely also interfere with microtubules needed for
axonal transport, accounting for taxane-induced
neurotoxicity that occurs in both large, myelinated
(proprioception, vibration) and small,
unmyelinated (temperature, pinprick) nerve fibers
• muscle stretch reflexes diminished in virtually all
patients
(Rock and DeMichele 2003; Windebank & Grisold 2008)
Copyright © The McGraw-Hill Companies, Inc. Used with permission
Consequences of Chemotherapy
to Normal Components of the
Muscular System
• skeletal muscles: problems such as
loss of balance or clumsiness result
from influence of chemotherapy drugs
on the PNS
• smooth muscles: functions in the
digestive tract may be impaired,
leading to stomach pain, constipation
• cardiac muscle: cardiotoxicity is a
well-known consequence of treatment
with anthracylines; can limit dosing
and scheduling with these drugs
Copyright © The McGraw-Hill Companies, Inc. Used with permission
Consequences of Chemotherapy to
Normal Components of the
Integumentary System
• mitosis is inhibited in stem
cells in the stratum basale
 hair loss
 itching
 dryness
 soft, discolored nails
 increased sun sensitivity
Copyright © The McGraw-Hill Companies, Inc. Used with permission
Consequences of Chemotherapy
to Normal Components of the
Digestive System
• mitosis inhibited in stem cells
throughout digestive tract, from
oral cavity to anus
• inability to replace these cells is
responsible for many digestive
problems associated with
chemotherapy
Copyright © The McGraw-Hill Companies, Inc. Used with permission
Consequences of Chemotherapy
to Normal Components of the
Digestive System
• mucositis: inflammation of the
mucosa of the entire digestive tract
• stomatitis, pharyngitis: inflammation
or sores in the mouth and throat
• oral hygiene can be challenging
• nausea & vomiting
• diarrhea
• constipation
• liver damage
Copyright © The McGraw-Hill Companies, Inc. Used with permission
Consequences of Chemotherapy
to Normal Aspects of Nutrition
& Metabolism
• appetite loss (anorexia)
 result of drugs directly or impact of
drugs on metabolism
• weight loss
 can result from anorexia, vomiting,
diarrhea
• weight gain
 can be caused by chemotherapy
regimens containing steroids;
inactivity; electrolyte imbalances,
fluid retention
Copyright © The McGraw-Hill Companies, Inc. Used with permission
Consequences of Chemotherapy
to Normal Components of the
Cardiovascular System: Heart
• anthracyclines well known for their
potential to damage the myocardium
(cardiotoxicity)

dose-limiting

symptoms: puffiness or swelling in the hands
& feet, shortness of breath that gets worse
with exercise or lying flat, dizziness, erratic
heartbeat, dry cough
• heart function checked (ECG,
echocardiogram) prior to starting
chemotherapy; regimen will be
terminated if problem develops
Copyright © The McGraw-Hill Companies, Inc. Used with permission
Consequences of Chemotherapy
to Normal Components of the
Cardiovascular System: Vessels
• edema can result from protein
deficiency
• some chemotherapy regimens, notably
docetaxel, cause capillaries to be leaky
 combined with fluid retention
associated with steroids coadministered with chemotherapy,
puffiness, fluid retention, and
weight gain result
• physical activity provides some relief
Copyright © The McGraw-Hill Companies, Inc. Used with permission
Consequences of Chemotherapy
to Normal Components of the
Lymphatic System
• edema can be improved with
physical activity
• greatest impact on lymphatic
system is the inability of existing
lymphocytes to be activated (= go
through mitosis) and the inability
of hemopoietic stem cells to
replace short-lived leukocytes,
increasing risk for infection
Copyright © The McGraw-Hill Companies, Inc. Used with permission
Consequences of Chemotherapy
to Normal Components of the
Reproductive Systems: Men
• chemotherapy may, through changes
in kidney function, alter the color or
odor of semen
• chemotherapy may alter hormone
balances, resulting in low testosterone
levels
• chemotherapy drugs may affect sperm
and testes, which may be permanent


freeze sperm prior to treatment
altered sperm can lead to birth defects;
safe sex practices advised
Copyright © The McGraw-Hill Companies, Inc. Used with permission
Consequences of Chemotherapy
to Normal Components of the
Reproductive Systems: Women
• many chemotherapy drugs can either
temporarily or permanently damage
the ovaries
 may alter hormone balances,
resulting in low fertility
 may chemically induce menopause
in women over 30
• chemotherapy drugs may result in
chromosomal abnormalities in oocytes

altered oocytes can lead to birth defects;
safe sex practices advised
Copyright © The McGraw-Hill Companies, Inc. Used with permission
Consequences of Chemotherapy
to Normal Components of the
Urinary System
• chemotherapy may
 irritate the bladder
 cause temporary or permanent
damage to the kidneys
• many problems can be prevented by
good fluid intake
• symptoms indicating problems
include:

pain or burning sensation during urination;
frequent urination; urgency; change in
urine color; fever, chills
CAN ANY OF THIS
BE AVOIDED??
Who Gets Cancer?
• half of all men and one-third of all women
in the US will develop cancer during their
lifetimes
• the sooner a cancer is found and treated, the
better the chances are for living for many
years
• today, millions of people are living with
cancer or have had cancer
(ACS 2008)
US Mortality, 2005
Cause of Death
No. of
deaths
1.
Heart Diseases
652,091 26.6
2.
Cancer
559,312 22.8
3.
Cerebrovascular diseases
143,597 5.9
4.
Chronic lower respiratory diseases
130,933
5.3
5.
Accidents (Unintentional injuries)
117,809
4.8
6.
Diabetes mellitus
75,119
3.1
7.
Alzheimer disease
71,599
2.9
8.
Influenza & pneumonia
63,001
2.6
9.
Nephritis
43,901
1.8
34,136
1.4
Rank
10. Septicemia
% of all
deaths
Sources: American Cancer Society and US Mortality Public Use Data 2005, National Center for Health Statistics, Centers for Disease
Control and Prevention, 2008.
2008 Estimated US Cancer Deaths*
Lung & bronchus
31%
Prostate
10%
Colon & rectum
8%
Pancreas
6%
Liver & intrahepatic
bile duct
4%
Leukemia
4%
Esophagus
4%
Urinary bladder
Men
294,120
Women
271,530
26%
Lung & bronchus
15%
Breast
9%
Colon & rectum
6%
Pancreas
6%
Ovary
3%
Non-Hodgkin
lymphoma
3%
3%
Leukemia
Non-Hodgkin
lymphoma
3%
3%
Uterine corpus
Kidney & renal pelvis
3%
2%
Liver & intrahepatic
bile duct
2%
Brain/ONS
All other sites
24%
25%
All other sites
ONS=Other nervous system. Source: American Cancer Society, 2008.
Risk Factors
• risk factor = anything that increases a
person's chance of getting a disease

some can be changed, others cannot
• known risk factors for cancer:
a person's age, sex, and family medical history
 environmental factors: exposure to radiation,
organic chemicals, pollutants
 lifestyle choices such as tobacco and alcohol
use, diet, and sun exposure
 which can be changed or modified?

Can Cancer Be Prevented?
• inheritance of genes containing mutations
that can increase risk cannot be changed
 vigilant screening for early detection
 prophylactic action
• reduce risk through behavior modification
don’t smoke, limit exposure to alcohol & sun
 diet: eat fresh vegetables & fruits, whole
grains; limit consumption of cured/smoked
meats, saturated & trans fats

Can Cancer Be Prevented?
“Research shows that about one-third of
all cancer deaths are related to dietary
factors and lack of physical activity in
adulthood.”
(ACS 2008)
Nutrition & Cancer Prevention
• Dietary Guidelines for Americans
 designed
to decrease risk for chronic diseases
such as cardiovascular disease, type 2 diabetes,
cancer
 MyPyramid: a menu-planning tool
 emphasizes/encourages
o
o
o
o
diet characterized by adequacy, moderation, balance,
and variety
whole and fresh foods, rather than processed
whole grains, vegetables & fruits
30-60 minutes of moderate exercise daily
Nutritional Factors That Can
Influence Cancer Risk
Dietary factors that may
increase cancer risk:
• heterocyclic amines and
nitrites/nitrates in meat
• obesity
• high fat diet
• alcohol
Dietary factors that may be
protective against cancer:
• antioxidants
• dietary fiber
• phytochemicals
• omega-3 (ω-3) fatty acids
(Thompson & Manore 2007)
What Are Antioxidants?
antioxidants = chemicals that protect cells
from damage from oxidation
• examples of nutrients with antioxidant properties:
 vitamins E, C, & A;
 the plant pigment beta-carotene; &
 trace mineral selenium (Se) in the enzyme
glutathione peroxidase
What Is Oxidation?
oxidation = a chemical reaction in which
atoms lose electrons

examples of oxidation reactions: metabolism!
• oxidation reactions are normally coupled
with reduction reactions (a molecule
accepting the electron is reduced)
• if oxidation reactions occur without
reduction reactions, free-radicals form
• free-radical formation is associated with
DNA damage and cancer!
Oxygen becomes an unstable, electronseeking free-radical
e-
e-
e-
e-
ee-
8P, 8N
e-
e-
e-
e-
e-
e-
e-
e-
ee-
8P, 8N
e-
e-
Free radicals can destabilize other molecules &
damage cells.
oxygen
freeradical
Oxidation and Free-Radical Formation
• free radicals damage electron-dense molecules and
structures as they seek out replacement electrons
 vulnerable
targets include cell membranes, low-density
lipoproteins (LDL), cellular proteins, and
DNA
• when a free radical steals an electron from another
molecule, the second molecule becomes unstable,
which then continues in a chain reaction
• chain reaction may damage proto-oncogene and/or
tumor-suppressor genes, leading to loss of control
of the cell cycle….
How Do Antioxidants Work?
• antioxidant vitamins donate their electrons to free
radicals to stabilize them
• antioxidant minerals act with complex enzyme
systems to destroy free radicals

e.g., glutathione peroxidase (selenium [Se])
• compounds such as β-carotene & phytochemicals help
stabilize free radicals & prevent damage to cells &
tissues
• supplementation with individual antioxidants does not
show consistent benefits: get antioxidants from food!
(Thompson and Manore 2007)
American Institute for Cancer Research
on Diet & Cancer Risk
• “AICR is the cancer charity that fosters research on diet and
cancer prevention, interprets the evidence, and educates the
public about the results.”
• Guidelines for Cancer Prevention:
 choose mostly plant foods, limit red meat, avoid
processed meat (plant foods are good sources of antioxidants)
 be physically active every day in any way for 30 minutes
or more
 aim to be a healthy weight throughout life
 and always remember: do not smoke or chew tobacco
(AICR 2008)
If proper nutrition can reduce
cancer risk, can proper nutrition
‘cure’ cancer?
Nutrition and Chemotherapy
The American Cancer Society on the use
of vitamin or mineral supplements
during chemotherapy treatment:
• “There is no single answer to this question,
but one thing is clear: No diet or nutritional
plan can "cure" cancer. Taking vitamin and
mineral supplements or any other
complementary and alternative medicine
should never be considered a substitute for
medical care. You should not take any
supplements without your doctor’s
knowledge and consent.”
Nutrition and Chemotherapy:
ACS Guidelines
• good nutrition is especially important when a person
has cancer because the illness and its treatments can
affect appetite and the body’s ability to tolerate certain
foods and use nutrients
• nutrient needs of cancer patients varies from person to
person; individual goals can be set by a registered
dietitian
• eating well can help the patient feel better; keep up
their strength, energy, and body’s store of nutrients;
tolerate treatment side effects; lower their risk for
infection; and heal & recover quickly
(ACS 2008)
Nutrition and Chemotherapy
• can proper nutrition prevent some of the
damage that happens to normal cells that
occurs during chemotherapy?
• various research studies have investigated
nutritional supplement use during
chemotherapy and/or radiation
Nutrition and Chemotherapy-induced…
• cardiotoxicity: “There has been no convincing
demonstration that nutritional agents can prevent
or forestall the progression of chemotherapy
(anthracyline)-induced cardiomyopathy.”
• bone loss: maintain adequate intakes of Ca+2 and
vitamin D, remain as physically active as possible.
• ovarian failure: no nutritional interventions with
success
(Rock & DeMichele 2003)
Nutrition and Chemotherapy-induced…
• peripheral neuropathy: various
neuroprotectants have been proposed and
examined in a variety of studies
acetyl-L-carnitine, glutathione, vitamin E
 antioxidants, in particular, have been studied
with great interest: but they are no more
selective for preventing damage to normal cells
than chemotherapy drugs are for destroying
cancer cells

(Lawenda et al., 2008)
Nutrition and Chemotherapy-induced
Peripheral Neuropathy
Latest research (analyses of multiple studies):
“CIPN remains a significant problem for
patients receiving chemotherapy for cancer.
At present, no interventions for CIPN can
be recommended for practice. No
rigorously designed studies, meta-analyses,
or systematic review support any of the
[dietary interventions] … and risk of harm
may outweigh potential benefits.”
(Visovsky et al., 2007)
Nutrition and Chemotherapy-induced
Peripheral Neuropathy
Latest research (analyses of multiple studies):
“On the basis of [our] review of the
published randomized clinical trials, [we]
conclude that the use of supplemental
antioxidants during chemotherapy and
radiation therapy should be discouraged
because of the possibility of tumor
protection and reduced survival.”
(Lawenda et al., 2008)
Nutrition and Chemotherapy-induced…
• neutropenia – this cannot be prevented or reversed by
nutritional means
• special precautions warranted!
 neutropenic diet, which restricts:
o
o
o
o
o
o
the use of ALL fresh fruits & raw vegetables (= cook!)
all nuts or seeds
the use of all garnish products
all dried fruits
all black pepper
any foods that are carriers of Pseudomonas aeruginosa
Hogan & Wane (2003)
Nutrition and Chemotherapy-induced
Neutropenia
• special precautions warranted!
 low bacterial diet, which restricts:
o
o
food that contain Gram-negative bacteria, molds, &/or
yeast
all fresh fruits or vegetables (= must be cooked)
 low
o
o
o
o
bacterial diet encourages:
use of proper food handling
food to be served within one hour at room temperature
no storage of leftover food > 24 hrs
cooking foods thoroughly to kill bacteria
Hogan & Wane (2003)
Summary
• most cancers occur in a time-dependent fashion,
the result of the accumulation of mutations in
genes associated with control of the cell cycle
• cancer most often originates in cells that
regularly and/or rapidly go through the cell
cycle
• no matter where it starts, cancer is often treated
locally (surgery, radiation) as well as
systemically (chemotherapy), and no matter
what the treatment is, it can hurt and make you
sick
Summary
• while the odds seem against us, we can reduce
our risk for developing cancer, and therefore
avoiding treatment, by eating right and
remaining physically active
• if we do get cancer, our chances of surviving
cancer as well as the treatment are better if we
already eat right and exercise
The message is simple:
Eat your vegetables!
Move around more!
and don’t forget,
References
Ahles TA, AJ Saykin, WW Noll et al. (2003) The relationship of APOE genotype to
neuropsychological performance in long-term cancer survivors treated with standard
dose chemotherapy. Psychooncology 12: 612-619.
Alessandri-Haber N, OA Dina, EK Joseph, DB Reichling, JD Levine. (2008)
Interaction of transient receptor potential vanilloid 4, integrin, and Src tyrosin kinase
in mechanical hyperalgesia. The Journal of Neuroscience 28: 1046 – 1057.
American Institute for Cancer Research (2008): http://www.aicr.org
Campbell NA, LG Mitchell and JB Reece (2000) Biology: Concepts & Connections,
3rd Edition. Benjamin Cummings, San Francisco, CA
Cancer Research UK: http://www.cancerhelp.org.uk
Ferguson, RJ, TA Ahles, AJ Saykin, BC McDonald, et al. (2007) Cognitive-behavioral
management of chemotherapy-related cognitive change. Psychooncology 16: 772 –
777.
Hede K (2008) Chemobrain is real but may need a new name. Journal of the National
Cancer Institute 100: 162-163, 169.
Hogan MA and D Wane (2003) Nutrition & Diet Therapy, Review & Rationales.
Prentice Hall, Upper Saddle River, NJ.
References
Inagaki M, E Yoshikawa, Y Matsuoka, et al. (2007) Smaller regional volumes of
brain gray and white matter demonstrated in breast cancer survivors exposed to
adjuvant chemotherapy. Cancer 109: 146 – 156.
Lawenda BD, KM Kelly, EJ Ladas, SM Sagar, A Vickers, and JB Blumberg. (2008)
Should Supplemental Antioxidant Administration Be Avoided During
Chemotherapy and Radiation Therapy? Journal of the National Cancer Institute
100(11): 773 – 783.
Mader, Sylvia (2006) Human Biology 9th Edition. McGraw-Hill Higher Education,
Boston, MA.
MyPyramid: www.mypyramid.gov , contains links to the Dietary Guidelines for
Americans. United States Department of Agriculture.
Rock E and A DeMichele. (2003) Nutritional approaches to late toxicities of
adjuvant chemotherapy in breast cancer survivors. Journal of Nutrition 133:
3785S – 3793S.
Saladin, KS (2007) Anatomy & Physiology, The Unity of Form & Function, 4th
Edition. McGraw-Hill Higher Education, Boston, MA.
Shier D, J Butler, and R Lewis (2004) Hole’s Human Anatomy and Physiology, 10th
Edition. McGraw-Hill Higher Education, Boston, MA.
References
Silverman DH, CJ Dy, SA Castellon, et al. (2006) Altered frontocortical, cerebellar,
and basal ganglia activity in adjuvant-treated breast cancer survivors 5-10 years
after chemotherapy. Breast Cancer Research and Treatment, available at
http://portfolio.psybrain.net/uploads/Psycho-onco/Silverman2006.pdf
The American Cancer Society: www.cancer.org
Thomspon J and M Manore (2007) Nutrition: An Applied Approach, MyPyramid
Edition. Pearson/Benjamin Cummings, San Francisco, CA
Visovsky, C, M Collins, L Abbott, J Aschenbrenner, and C Hart (2007) Putting
Evidence Into Practice: Evidence-based interventions for chemotherapy-induced
peripheral neuropathy. Clinical Journal of Oncology Nursing 11: 901 – 913.
Windebank AJ and W Grisold (2008) Chemotherapy-induced neuropathy. Journal
of the Peripheral Nervous System 13: 27 – 46.
Wolf S, D Barton, L Kottschade, A Grothey, and C Loprinzi. (2008) Chemotherapyinduced peripheral neuropathy: Prevention and treatment strategies. European
Journal of Cancer 44: 1507 – 1515.
I am grateful to Evelyn K Hayes, M.D., for the image illustrating the progression of
cervical neoplasia.