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Cellular Aberration

Merchie Lissa T. Alabat, RN

June 13, 2013

Objectives:
After 3 hours of discussion, the students will be able to:
Define Cancer
Discuss recent cancer statistics in the Philippines
Compare the features of benign and malignant cells
Discuss and trace cancer development according to
its pathophysiology and mechanisms
Enumerate etiologies for cancer
List means of cancer prevention
Enumerate diagnostic techniques for detecting
cancer

CANCER
A disease whereby cells mutate into abnormal
cells that proliferate abnormally
Neoplasia- new cell growth; a mass of new
tissue functioning independently and serving
no useful purpose
Benign
Malignant
Medical term for cancer: Malignant Neoplasm

Oncology- study of cancer


Oncology/Cancer Nursing- field of
nursing with a specialization in
cancer care
Scope, responsibilities and goals are
as diverse and complex as those of
any nursing specialty

More common today especially in


more affluent countries
In February 2010, the World Health
Organization (WHO) predicted that
the number of cancer deaths in
worldwide will increase from 7.6
million to 17 million deaths in 2030.

Philippine Cancer
Statistics
In 2006, malignant neoplasm ranked
3rd in the 10 Leading Causes of
Mortality with 43,043 recorded deaths
growing by 5% every year as per
population growth and increase in
smoking prevalence (DOH)
Out of this 43,043 deaths, 22,472 are
males and 20,571 are females

Philippine Cancer
Statistics
Breast cancer is also the leading cause
of cancer among women, accounting
for 28% of the total cases, followed by
cancer of the cervix, ovary, thyroid and
lung.
Lung cancer, meanwhile, is the most
common cancer for men at 27 % of the
total cases, followed by liver, prostate,
colon and rectum

Leading cancer sites/types are:


1.Breast
2.Lung
3.Liver
4.Cervix
5.Colon
6.Thyroid
7. Rectal
8.Ovaries
9.Prostate
10.Lymphatic Tissue (Non-Hodgkins
Lymphoma

Biology of Cells

Building Blocks of Cells


Carbohydrates
Carbohydrates are comprised of carbon
(C), hydrogen (H), and oxygen (O)
molecules.
Sugars are common carbohydrates.
Carbohydrates serve several functions
inside cells:
Major energy source
Provide structure
Communication
Cell adhesion
Defense against and removal of foreign
material

Proteins
Proteins are comprised of amino acids.
Proteins serve several functions inside
living things:
Structure of hair, muscle, nails, cell
components, and cell membranes
Cell transport
Biological catalysts or enzymes
Maintaining cell contact (fibronectin)
Control cell activity
Signaling via hormones

Lipids
A wide variety of biomolecules including fats, oils,
waxes and steroid hormones.
Lipids do not dissolve in water (they are
hydrophobic) and are primarily comprised of carbon
(C), hydrogen (H), and oxygen (O).
Lipids serve several functions in living things:
Form biological membranes
Fats may be stored as a source of energy
Oils and waxes provide protection by coating
areas that could be invaded by microbes (i.e. skin
or ears)
Steroid hormones regulate cell activity by
altering gene expression

Nucleic Acids
All of the information needed to control and
build cells is stored in these molecules.
Nucleic acids are comprised of nucleotides
which are abbreviated as A, C, G, T, and U.
There are two main types of nucleic acid,
deoxyribonucleic acid (DNA) and ribonucleic
acid (RNA)

Cells and Cell Structure


Organelles
Organelles are structures that carry out
different functions within a cell.
Organelles in a cell are analogous to the
organs in a body.
Organelles are suspended in a water-based
fluid called cytosol.

The Nucleus
Nucleus can be thought of as the
brains of a cell.
Genetic material is stored in this
organelle.
The nucleus (plural-nuclei) is
roughly spherical and is surrounded
by two membranes.
Home to chromosomes.

Nucleus

The Mitochondrion
(Singular- mitochondrion) Mitochondria are
the power houses of a cell.
Mitochondria convert biomolecules (i.e.
fats and sugars) into energy.
By-products of energy production in
mitochondria may damage DNA and cause
mutations. are the energy powerhouses of
cells

The Ribosome
Ribosomes are made up of two large
complexes comprised of RNA and protein.
Ribosomes are located in the cytosol. Their
function is to read RNA and produce
proteins in a process known as translation.

The Cytoskeleton
The cytoskeleton is an intricate network of
proteins that criss-cross the cytoplasm of a
cell.
Actin and tubulin are the proteins used to
build main fibers of the cytoskeleton
(microfilaments and microtubules,
respectively).

The cytoskeleton serves several key


functions:
Provides structure to cells and a place to anchor
organelles
Cell motility
Control of cell division during mitosis

Changes in the cytoskeleton that allow


increased movement are observed in cancer
cells.
Many anti-cancer drugs work by interfering
with the activity of cytoskeletal proteins.

Cell Division and Mitosis


The process by which a cell reproduces
to create two identical copies of itself is
known as Mitosis.
2 reasons for mitosis:
Develop normal tissue
To replace lost or damaged normal tissue

In order for this to happen, the following


must occur:
The genetic material, the DNA in chromosomes,
must be faithfully copied. This occurs via a
process known as replication.
The organelles, such as mitochondria, must be
distributed so that each daughter cell receives an
adequate amount to function.
The cytoplasm of the cell must be physically
separated into two different cells.

Cell cycle- cell division process occurring at


an orderly progression through four different
stages.
4 Stages:

G1- G stand for gaps; cell is preparing to divide. The


cells take in more nutrients, making more energy.
S- stands for synthesis. This is the phase of the cell cycle
in which the DNA is copied or replicated.
G2- cell makes important proteins that will be used in
cell division and in normal physiologic functioning after
cell division is complete.
M- stands for mitosis. This is the stage of the cell cycle in
which the cell actually divides into two daughter cells.

Characteristics of
Normal &
Malignant Cells

Characteristic

Normal Cell

Malignant
Cell

Cell Division

None or slow

Rapid or continuous

Appearance

Specific
morphology

Anaplastic

Nuclear-cytoplasmic
ratio

Small

Large

Differentiated
functions

Many

Some or more

Adherence

Tight

Loose

Migratory

No

Yes

Growth

Well regulated

Invasion

Chromosomes

Diploid (euploid)

Aneuploid

Mitotic index

Low

High

Genetic Mutation in
Cancer
Mutations in key regulatory
genes
Proto-oncogenes
Tumor suppressors

Causes of Genetic Change


Spontaneous Mutations - mutations
resulting from unrepaired replication errors or
random molecular events
Induced Mutations - mutations caused by
things such as radiation, chemicals,
chronic inflammation, and oxygen radicals.
Abnormal Cell Division - problems in cell
division can result in mutations
Viruses - some viral infections can cause
mutations

Cancer Types
The following terms are commonly used to
distinguish tumors of different origin
Carcinoma- a tumor derived from epithelial cells
Sarcoma- a tumor derived from muscle, bone,
cartilage, fat or connective tissues
Leukemia- a cancer derived from white blood cells
or their precursors.
Lymphoma- a cancer of bone marrow derived cells
that affects the lymphatic system.
Myelomas- a cancer involving the white blood cells
responsible for the production of antibodies (B
lymphocytes or B-cells).

Welcome to another day


of knowledge! Listen up,
it will do you good!
Get ready!!!

Quiz #1
Instruction:
Fill in the missing data in the table. Write
ONLY the answer on your sheet of paper.

Characteristic

Normal Cell

Malignant
Cell

Cell Division

None or slow

1.

Appearance

2.

Anaplastic

Nuclear-cytoplasmic
ratio

3.

4.

Differentiated
functions

5.

Some or more

Adherence

6.

Loose

Migratory

No

Yes

Well regulated

7.
8.

Growth
Chromosomes
Mitotic index

Diploid (euploid)

Characteristic

Normal Cell

Malignant
Cell

Cell Division

None or slow

Rapid or continuous

Appearance

Specific
morphology

Anaplastic

Nuclear-cytoplasmic
ratio

Small

Large

Differentiated
functions

Many

Some or more

Adherence

Tight

Loose

Migratory

No

Yes

Growth

Well regulated

Invasion

Chromosomes

Diploid (euploid)

Aneuploid

Mitotic index

Low

High

CARCINOGENESIS/ONCOGENESIS/CANCER
DEVELOPMENT
Malignant Transformation- the process of
changing a normal cell into a cancer cell
1.
2.
3.
4.

INITIATION
PROMOTION
PROGRESSION
METASTASIS
Metastatic Mechanisms

Metastatic Mechanisms
Lymphatic spread- transport of tumor
cells through the lymphatic circulation
Hematogenous spread- malignant
cells are disseminated through the
blood stream; enzymes make large
pores into the clients blood vessel
allowing tumor cells to enter the blood
and circulate throughout the body

Angiogenesis- induce the growth of


new capillaries from the host tissue to
meet their needs for nutrients and
oxygen; through this process that
tumor emboli can enter through the
systemic circulation and travel into
distant sites

Cancer cell invasion and metastasis. (i) Cancer cell


invasion of surrounding tissue. (ii) Angiogenesis and
cancer cell transportation via the circulatory system. (iii)
Cancer cell metastasis (spreading from a primary site)
and growth at a new location.

CANCER
ETIOLOGY

CANCER ETIOLOGY
Oncogene Activation- activation
of proto-oncogenes into oncogenes
can cause the cell to change
from normal cells to cancerous cells
Example:
MYCL- Lung Cancer
Ki-RAS- Colorectal Cancer

External Factors Causing


Cancer
Chemical Carcinogenesis- produce
their toxic effect by altering DNA
structures in body sites distant from
chemical exposure
Tobacco smoke- single most lethal chemical
carcinogen; initiates and promotes cancer
Found in 30% of all malignant neoplasms

Tobacco smoke+alcohol- co-carcinogens

Examples:
Amine/aniline dyes
Pesticides
Formaldehyde
Arsenic
Soot and tar
Asbestos
Nickel and zinc ores
Etc.

Physical Carcinogens- cause cancer by


same mechanism as for chemical agents
Radiation
2 types of radiation:
Ionizing- some found naturally in such
elements as radon, uranium and radium;
x-rays, cosmic radiation
Utraviolet- solar radiation; tanning
beds, germicidal lights; clothing styles,
use of sunscreen, occupation,
recreational habits

Chronic irritation
Irritated tissue frequent cell
divisions and are at an increased
risk of DNA mutation
E.g. Tissue trauma; burn scars
skin cancer

Viruses [Oncoviruses]
Viruses as a cause for human cancer
are hard to determine because
viruses are difficult to isolate
When viruses infect body cells, they
break the DNA chain and insert their
own genetic material into the human
DNA chain
E.g. Hepatitis B virus Primary liver
carcinoma; Human Papilloma virus
Cervical Carcinoma

Dietary Factors
Risk for cancer increases with
long-term
ingestion
of
carcinogens or chronic absence of
proactive substances in the diet
Include: fats, alcohol, salt-cured or
smoked meats, foods containing
nitrates and nitrites, and a high
caloric dietary intake

Food substances that appear to


reduce cancer risk are as follows:
High-fiber foods
Cruciferous vegetables (cabbage,
broccoli, cauliflower)
Carotenoids (carrots, tomatoes,
spinach, apricots, dark-green and deepyellow vegetables)
Vit. E and C, zinc, and selenium

Hormonal Agents
Tumor growth may be promoted by
disturbances in hormonal balance
either by the bodys own
(endogenous hormone) production
or by administration of exogenous
hormones
Cancer of breast, prostate, and
uterus are thought to depend on
endogenous hormonal levels for
growth

DES (Diethylstilbestrol) vaginal


carcinomas
Oral contraceptives & prolonged
estrogen therapy
hepatocellular, endometrial and
breast cancer
Hormonal changes with
reproduction

Personal Factors
Immune Function- non-self cells that are
no longer normal cancer cells
Cell-mediated immunity- part of the
immune system that helps protect
against cancer
Natural killer (NK) and helper T-cells provide
immune surveillance
Immunosuppressed- increased cancer incidence
Organ transplant recipients
HIV/AIDS- cancer incidence is as high as 70%

Age
Advancing age is the single most important risk
factor for cancer (American Cancer Society)
Manifestation of cancer in older adults may be
overlooked as changes of normal aging
Older adults must be aware of the 7 warning signs of
cancer (CAUTION) by American Cancer Society
C changes in bladder or bowel habits
A a sore that does not heal
U unusual bleeding or discharge
T thickening or lump in the breast or elsewhere
I indigestion or difficulty swallowing
O obvious change in wart or mole
N nagging cough or hoarseness

Genetic Risk
Familial patterns
Inherited genetic defects

PATHOPHYSIOLOGY
of
CANCER

NORMAL
CELL
ACQUIRED
Carcinogens: chemicals,
INITIATION
radiation, viruses

PREDISPOSING/
ETIOLOGIC
FACTORS

DNA Mutation

Conversion of
proto-oncogenes to
oncogenes

Inhibition of tumor
Suppressor genes

Inhibition of DNA repair


genes

Decreased
apoptosis

Unregulated cell
proliferation

PROMOTION Clonal expansion


Of a pre-cursor cell
PROGRESSION
METASTASIS
Tumor
progression

MALIGNANT
NEOPLASM

CANCER CLASSIFICATION
Classified by type of tissue/tissue of origin
from which they arise
Prefix- adeno, lympho, melano
Tissue of origin- epithelial glands, lymphoid
tissues, pigment-producing skin
Suffix- benign tumor: -oma
malignant tumor: -coma, -sarcoma,
-carcinoma
e.g. adenoma (benign); adenorcarcinoma
(malignant)

Type of Tissues/Tissue
Origin

PREFIX

TISSUE TYPE

BENIGN
TUMORS

MALIGNANT
TUMORS

Adeno

Epithelial glands

Adenoma

Adenocarcinoma

Neuro

Nerve tissue

Neuroma

Neurosarcoma

Osteo

Bone

Osteoma

Osteosarcoma

Renal

Kidney

Renal Cell Carcinoma

Melano

Skin (Pigmentproducing)

Melanoma

Hepato

Liver

Hepatoma

Hepatosarcoma

Cancer
Detection

Cancer Grade and Stage


Developed to help standardize cancer
diagnosis, prognosis, and treatment
Accomplished before treatment begins to
provide baseline date for evaluating
outcomes of therapy
Treatment options and prognosis are
determined on the basis of staging and
grading.

Grading
One of the first steps in confirming cancer
Refers to the classification of tumor cells
Seek to define the type of tissue from w/c
the tumor originated and the degree to
which the tumor cell retain the functional
and histologic characteristics of the tissue of
origin
Samples of cells for tumor grading may be
obtained through cytology, biopsy or
surgical excision

Grade

Cellular Characteristics

Gx

Grade cannot be determined

G1

Tumor cells are well differentiated and closely resemble the


normal cell from which they arose; malignant but are slow
growing

G2

Tumor cells are moderately differentiated; still retain some


of the characteristics of normal cells but also have more
malignant characteristics than do G1 tumor cells

G3

Tumor cells are poorly differentiated, but the tissue of origin


can usually be established

G4

Tumor cells are poorly differentiated and retain no normal cell


characteristics; determination of the tissue of origin is difficult and
perhaps impossible

Staging
Determines the exact location of the
cancer and its degree of metastasis at
diagnosis
Influences selection of therapy
Done in 3 ways:
1. Clinical Staging
2. Surgical Staging
3. Pathologic Staging

Specific staging system include Dukes


staging of colon and rectal cancer and
Clarks level method of staging skin
cancer

TNM (tumor, node, metastasis)


system to describe the anatomic
extent of cancer
T- the extent of the primary tumor
N- the absence or presence and extent of
regional lymph node metastasis
M- the absence or presence of distance
metastasis

Guide treatment and are useful at prognosis


and comparison of treatment results
Have specific prognostic value for each solid
tumor type

Primary Tumor (T)

Tx

Primary tumor cannot be assessed

T0

No evidence of primary tumor

Tis

Carcinoma in situ

T1, T2, T3, T4

Increasing size and/or local extent of


the primary tumor

Regional Lymph Nodes (N)


Nx

Regional lymph node cannot be assessed

N0

No regional lymph node metastasis

N1, N2, N3, N4

Increasing involvement of regional lymph


nodes

Distant Metastasis (M)


Mx

Presence of distant metastasis cannot be


assessed

M0

No distant metastasis

M1

Distant metastasis

Example of StagingBreast Cancer


Stage I: T1-tumor 2 cm or less in diameter; N0no lymph nodes involved; M0- no metastasis
Stage II: T0 to T2- tumor less than 5cm in
diameter; N1- nodes involved; M0- no
metastasis
Stage III: T3- tumor larger than 5cm in
diameter; N1 or N2- nodes involved, tumor
may be fixed; M0- no metastasis
Stage IV: T4- tumor any size but fixed to chest
wall or skin; N3- clavicular nodes involved
(spread); M1- metastasis present

DIAGNOSTIC
EXAMINATIONS

Invasive Techniques
Fine needle aspiration (FNA) uses a
small needle to collect small samples
of a lesion.
Core needle biopsy (BPA) uses a
larger needle to collect samples of a
lesion.

Pap smears- use a sample of cells from


the cervix to detect cervical cancer. Pap
smears may also detect ovarian and
uterine cancers that have migrated to the
cervix.

Colonoscopy uses a small tube containing


viewing equipment to view the colon.

Endoscopy- Direct visualization of a


body cavity or passageway by insertion
of an endoscope into a body cavity or
opening

Non-invasive Techniques
Ultrasound- uses reflection of sound
waves to create an image of a part of the
body

MRI- uses magnetic fields and radio waves


to produce images of the body.

CT scans- use x-rays to take multiple


image slices in order to create a 3D
image.

PET scans- use radioactive molecules to


create a dynamic image of internal tissues
and organs. PET scans are able to measure
the metabolic activity of cells, not just their
structure.

X-rays- utilize high energy beams to


create an image.

Chest x-ray showing lung


cancer in the left lung

Mammography uses low dose x-ray to


create an image of a breast.

Normal Breast

Breast with tumor

TEST

Tumor Identification
Marker

DIAGNOSTIC USES
Breast, colon, lung,
ovarian, testicular,
prostate cancers

MRI

Neurologic, pelvic,
abdominal, thoracic
cancers

CT scan

Neurologic, pelvic, skeletal,


abdominal, thoracic cancers

TEST

Fluoroscopy

DESCRIPTION
Use of x-rays to identify
contrasts in body tissue
densities; may involve
the use of contrast
agents

DIAGNOSTIC USES
Skeletal, lungs, GI
cancers

Ultrasound

Abdominal and
pelvic cancers,
Breast Cancer

Endoscopy

Bronchial, GI
cancers

Sigmoidoscopy/
Colonoscopy

Colon cancer

TEST

Nuclear
medicine
imaging
e.g. PET scan

DESCRIPTION
Uses intravenous
injections or
ingestion of
radioisotope
substances
followed by
imaging of tissues
that have
concentrated the
radioisotopes

DIAGNOSTIC
USES
Bone, liver, kidney,
spleen, brain,
thyroid cancers
Lung, colon, liver,
pancreatic, breast,
esophagus cancers;
Hodgkins & nonHodgkins
lymphoma &
melanoma

Analysis of
Biopsy/Cytology Samples
Immunohistochemistry (IHC)- measures
protein expression using specially labeled
antibodies.
Fluorescence in situ hybridization (FISH)measures genetic changes (i.e. amplification)
using fluorescently labeled DNA probes.

Tumor Identification Marker


Analysis of substance found in blood and
other body fluids that are made by the
tumor or by the body in response to the
tumor

Tumor marker- protein substances found


in the blood or body fluids
Derived from the tumor itself

Tumor Markers
Tissue-specific antigens- identify the type
of tissue affected by malignancy
E.g. Prostate Specific Antigen (PSA) to
identify prostate cancer

Oncofetal Antigens- present normally in


fetal tissue, may indicate an anaplastic
process in tumor cells
E.g. Carcinoembryonic Antigen (CEA),
Alfafetoprotein (AFP)

Hormones- present in large quantities in a


body with cancer
Antidiuretic hormone (ADH), Human
Chorionic Gonadotropin (HCG)

Isoenzymes- present in the blooodstream


if tissue is experiencing rapid, excessive
growth as the result of a tumor
E.g. Prostatic Acid Phosphatase (PAP)

Cancer
Prevention

Primary Prevention
Avoidance of known or potential
carcinogens
Modification of associated factors
Removal of at risk tissues
Chemoprevention
Use of drugs, chemicals, natural
nutrients or other substances to
disrupt one or more steps in cancer
development

Chemoprevention
Category of Prevention

Specific Agents

Prevention of carcinogen
formation

Vit.C, Vit. E, Selenium, caffeic acid

Antimutagen

Carotenoids, retinoids, flovones

Enhancing the elimination of a


carcinogen

Indole 3 Carbinol, isothiocyonate

Suppression of carcinogenic
action

Aspirin, Selenium, SAIDs

Antipromotion activity

Carotenoids, selenium, piroxicam

Suppression of progression

Danazol, Interferon

Secondary Prevention
Screening programs
Recommended screenings (American Cancer Society)
Beginning at age 20, routinely perform BSE
Yearly mammography for women older than 40
years
Yearly clinical BSE for women older than 40 years
Yearly Pap Smear for sexually active females and any
female over 18 years
Colonoscopy at age 50 years and then q10 years
Yearly FOBT in adults of all ages
Yearly PSA test and digital rectal exam for men over
50 years
Screening programs should be based on an individuals
age, sex, family history of cancer, ethnic group or race

Gene therapy for cancer


prevention
E.g. of gene mutations:
BRCA 1 gene- increases the risk for breast and
ovarian cancer
BRCA 2- increases the risk for breast cancer
APC gene- increases the risk for colon cancer

Cancer Prevention
7 steps to reduce risk recommended by Mayo
Clinic:
1.
2.
3.
4.
5.
6.
7.

Don't use tobacco


Eat a variety of healthy foods
Stay active and maintain a healthy weight
Protect yourself from the sun
Get immunized
Avoid risky behaviors
Get screened

Thank you for listening!

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