Cancer Pathogenesis, Warning Signs and Prevention

Carcinogens, Pathogenesis , Warning
signs and Prevention of Cancer
Ms. Sunita Kharel
M.Sc. Nursing 2019 Batch
Department of Medical Surgical Nursing

Outline
• Introduction to cell
• Cell cycle
• Checkpoint
• Inhibitors
• Regulation of cell cycle
• Carcinogenesis
• Tumor growth
• Role in tumor formation
• Pathophysiology
• Characteristics of neoplastic
cells 2
• Metastatic process
• Growth of neoplastic
tumor
• Classification of
malignant tumor
• Warning signs of cancer
• Preventive measures of
cancer
• Conclusion
10/8/2021 Ms. Sunita Kharel, Carcinogenesis

What is Carcinogenesis?
10/8/2021 Ms. Sunita Kharel, Carcinogenesis 3

Anatomy and Physiology of Cell
• The cell is the basic building
block of living organisms.
• Most cells are spherical or cube
shaped but some are a range of
different shapes.
• Most cells are so small that a
microscope is needed to see
them.
• A normal cell is about 0.02 of a
millimetre (0.02mm).

Anatomy and Physiology of Cell…
• When we look at a typical animal cell with a light
microscope it seems quite simple with only a few
structures visible.
• Three main parts can be seen:
– an outer cell membrane (plasma membrane),
– an inner region called the cytoplasm and
– the nucleus

• Nucleus is a membrane-
bound organelle found
in eukaryotic cells.
• The nucleus is the largest organelle in
animal cells.
• Nucleus contains the majority of the
cell's genetic material in the form of
multiple linear DNA molecules
organized into structures
called chromosomes.

Cell Cycle
 The cell cycle, or cell-division cycle, is the
series of events that take place in a cell leading
to its division and duplication (replication).

G1 - first gap
S - DNA synthesis (replication)
G2 - second gap
M - mitosis

 In cells without a nucleus (prokaryotic), the cell cycle
occurs via a process termed binary fission.
 In cells with a nucleus (eukaryotes), the cell cycle can
be divided in two periods:
i. Interphase
ii. Mitosis
Cell Cycle…

Cell Cycle…
 Interphase- during which the cell grows, accumulating
nutrients needed for mitosis and duplicating its DNA
 Mitosis (M) phase- during which the cell splits itself
into two distinct cells, often called "daughter cells" and
the final phase, cytokinesis, where the new cell is
completely divided.

Interphase
• Before a cell can enter cell division, it needs to take
in nutrients. All of the preparations are done during
the interphase.
• Interphase proceeds in three stages, G1, S, and G2.
Cell division operates in a cycle.
• It is also known as preparatory phase, in this stage
nucleus and cytosol division does not occur. The
cell prepares to divide.

G1 phase
• The first phase within interphase, from the end of the
previous M phase until the beginning of DNA
synthesis is called G1 (G indicating gap).
• It is also called the growth phase. During this phase
the biosynthetic activities of the cell, which had been
considerably slowed down during M phase, resume
at a high rate.
• This phase is marked by synthesis of 20 amino acids
which then form millions of proteins and later on
enzymes that are required in S phase, mainly those
needed for DNA replication.

S phase
 The S phase starts when DNA synthesis commences;
when it is complete, all of the chromosomes have
been replicated, i.e., each chromosome has two
(sister) chromatids.
 Thus, during this phase, the amount of DNA in the
cell has effectively doubled, though the ploidy of the
cell remains the same.

G2 phase
• The cell then enters the G2 phase, which lasts until
the cell enters mitosis.
• Again, significant biosynthesis occurs during this
phase, mainly involving the production of
microtubules, which are required during the process
of mitosis.
• Inhibition of protein synthesis during G2 phase
prevents the cell from undergoing mitosis.

Mitosis (M Phase/Mitotic phase)
 The relatively brief M phase consists of nuclear
division (karyokinesis). The M phase has been
broken down into several distinct phases,
sequentially known as:
o prophase,
o metaphase,
o anaphase,
o telophase
 cytokinesis (strictly speaking, cytokinesis is not
part of mitosis but is an event that directly
follows mitosis in which cytoplasm is divided
into two daughter cells)

• Mitosis is the process by which a eukaryotic cell
separates the chromosomes in its cell nucleus into two
identical sets in two nuclei.
• It is generally followed immediately by cytokinesis,
which divides the nuclei, cytoplasm, organelles and
cell membrane into two cells containing roughly
equal shares of these cellular components.
• Mitosis and cytokinesis together define the mitotic
(M) phase of the cell cycle - the division of the
mother cell into two daughter cells, genetically
identical to each other and to their parent cell. This
accounts for approximately 10% of the cell cycle.

Checkpoints
 Cell cycle checkpoints are used by the cell to
monitor and regulate the progress of the cell
cycle.
 Checkpoints prevent cell cycle progression at
specific points, allowing verification of necessary
phase processes and repair of DNA damage.
 The cell cannot proceed to the next phase until
checkpoint requirements have been met.
 Several checkpoints are designed to ensure that
damaged or incomplete DNA is not passed on to
daughter cells.

Checkpoints…
 Two main checkpoints exist: the
G1/S checkpoint and the G2/M
checkpoint.
 G1/S transition is a rate-limiting
step in the cell cycle and is also
known as restriction point. An
alternative model of the cell cycle
response to DNA damage has also
been proposed, known as the
postreplication checkpoint plays
an important role in triggering the
control mechanisms at both G1/S
and G2/M checkpoints.

Inhibitors
• Overview of signal transduction pathways involved in apoptosis,
also known as "programmed cell death".
• slow or stop cell cycle progression through various mechanisms.
• Cell cycle arrest can be induced at different stages, decreasing
the rate of cell division and the number of actively cycling cells.
• Two families of genes, the cip/kip family (CDK interacting
protein/Kinase inhibitory protein) and the INK4a/ARF (Inhibitor
of Kinase 4/Alternative Reading Frame) prevent the progression
of the cell cycle.
• Because these genes are instrumental in prevention of tumor
formation, they are known as tumor suppressors.

Regulation of Eukaryotic cell cycle
• Regulation of the cell cycle involves processes crucial to
the survival of a cell, including the detection and repair
of genetic damage as well as the prevention of
uncontrolled cell division.
• The molecular events that control the cell cycle are
ordered and directional; that is, each process occurs in a
sequential fashion and it is impossible to "reverse" the
cycle.
 Two key classes of regulatory molecules, cyclins and
cyclin-dependent kinases (CDKs), determine a cell's
progress through the cell cycle. 23

Role of cyclin and cyclin dependent
kinase
• Cyclins drive the events of the cell cycle by partnering
with a family of enzymes called the cyclin dependent
kinase (CDKs).
• CDK alone is inactive but the binding of the cyclin
activates it, making it a functional enzymes.
• This functional enzymes cause a reaction inside the cell
that cause E2f to detach from the retinoblastoma
protein.
• When E2f is released, its acts like a transcription factor
allowing that particular cell to progress through the S
phase.
• So CDk and cyclins are the drivers of the cell cycle.

• p53, also known as TP53 or tumor protein is a gene
that functions as a tumor suppression.
• P53 and P family gene helps in
– Growth arrest thereby preventing replication of
damaged DNA.
– DNA repair
– Apoptosis (cell death) to avoid proliferation of cells.

Cancer
• Cancer is a group of diseases characterized by the
uncontrolled growth and spread of abnormal cells.
• Cancer is a generic term for a large group of
diseases that can affect any part of the body.
• Other terms used are malignant tumors and
neoplasms.
• Not all tumors are cancerous; benign tumors do not
spread to other parts of the body.
• There are over 100 different known cancers that
affect humans.

Carcinogenesis
• Also called oncogenesis or tumorigenesis.
• The formation of a cancer, whereby normal cells
are transformed into cancer cells.
• The process is characterized by changes at the
cellular, genetic, and epigenetic levels and
abnormal cell division.
• Agents which can induce tumors are called
carcinogens.

Role in tumor formation
• A disregulation of the cell cycle components may lead to
tumor formation.
• As mentioned above, some genes like the cell cycle
inhibitors. when they mutate, may cause the cell to multiply
uncontrollably, forming a tumor.
• If one have too much cyclin and CDK , then one gets
uncontrolled growth of cells.
• Also mutation of P53 gene also can cause the tumor in the
body.

Theories of Carcinogenesis
• Genetic theory
• Epigenetic theory
• Immune surveillance theory
• Monoclonal hypothesis
• Multistage theory

Genetic theory
• The most popular theory
• Cells become neoplastic because of alterations
or structural anomalies in the DNA.
• Many physical (e.g. radiation ) and chemical
agents causing cancer bring about mutation in
the host cells.

Epigenetic Theory
• The carcinogenic agents act on activators or
suppressors of genes and not on the genes
themselves and result in the abnormal expression
of genes.
• It is rarely accepted.

Immune Surveillance Theory
• An immune competent host mounts an attack on
developing tumor cells so as to destroy them
while an immune-incompetent host fails to do so.
• There is high incidence of cancer in immuno-
deficient individuals. E.g. in AIDS.
• Most cancers occur more frequently in old age
when the host immune responses are weak.

Monoclonal Theory
• Strong evidence on studies of human and
experimental tumors that most cancers rise
from a single clone of transformed cells.

Multistage Theory
• This theory seems to be generally accepted.
• Carcinogenesis is a multistage process, since
between the initial carcinogenic stimulus and the
final manifestation of cancer , there are several
stages.
• The appearance of a population of neoplastic
cells can be divided in the following stages:
initiation, promotion and progression.

Pathophysiology of cancer:
 Cancers are caused by a series of mutations. Each
mutation alters the behavior of the cell somewhat.
 The 1st steps in a healthy cells becoming a cancer cell
is the change of the proto-oncogenes to oncogenes.
Proto-oncogenes are gens that are coded to maintain
normal cell growth.
 An oncogene is a gene that has changed to make the
cell grow and divide faster. E.g. RAS gene, MYC gene.

Pathophysiology …
• The 2nd step to becoming a cancer cell is: the tumor
suppressor gens turned off. E.g. P53, APC, BRCA1/2
• Tumor suppressor gens are a part of a healthy cells
DNA that help stop cancer from forming in healthy
cells.
• Tumor suppressor genes help slow down cell growth,
when these genes are turned off the cells will grow and
divide very quickly.

Pathophysiology…
• The last step to becoming a cancer cell is: the DNA
repair genes get turned off.
• DNA repair genes help healthy cells know if some
thing is wrong with its DNA and how to fix it.
• When these genes get turned off the cell does not
know if it is sick and it can't fix any problems with
its DNA.

Metastatic process:
• A metastasis is the process of spreading the cancerous
cells from the primary site of origin, or where it
started, into different areas of the body.
• Metastasis happens in different ways:
– Invasion of neoplastic cells from the primary tumor into
surrounding tissue and penetrating of blood and lymph
vessels
– Spread of tumor cells via the lymph/blood circulation or
by direct expansion
– Establishment and growth of tumor cells at the
secondary site.

Characteristics of neoplastic cells:
In appearance, neoplastic cells are usually larger than
normal cells and they have a bigger nucleus.
Differ substantially from each other in terms of size
and shape, while normal cells are more homogenous
Anaplastic cells –grows into disorganized, irregular
cellular sheets
Flourish in antagonistic physical, chemical, hormonal
and viral environment

Classification of Malignant Tumours
(TNM) is a cancer staging notation system that gives codes
to describe the stage of a person's cancer, when this
originates with a solid tumor.
• T describes the size of the original (primary) tumor and
whether it has invaded nearby tissue.
• N describes nearby (regional) lymph nodes that are
involved.
• M describes distant metastasis (spread of cancer from
one part of the body to another).

• Most of the common tumors have their own TNM
classification.
• Not all tumors have TNM classifications, e.g., there is
no TNM classification for brain tumors.

Staging:
The extent of disease classification is often called ‘staging’:
This type of classification is used as a basis for staging in cancer of
cervix and Hodgkin’s disease.
Stage Extend
0 Cancer in situ. It is defined as a neoplasm of epithelial tissue
that remains confined to the site of origin.
I Tumor linked to the tissue of origin, localized tumor growth
II Limited local spread.
III Extensive local and regional spread.
IV Metastasis.

Seven warning signs of cancer
C Change in bowel or bladder habits
A A sore that does not heal
U Unusual bleeding or discharge from anybody
orifice
T Thickening or a lump in the breast or
elsewhere
I Indigestion or difficulty in swallowing
O Obvious change in a wart or mole
N Nagging cough or hoarseness

A. Primary Prevention - trying
to prevent oneself from getting a cancer.
B. Secondary Prevention - trying to detect a
cancer early and prevent it from getting
worse.
C. Tertiary Prevention - trying to improve
quality of life and reduce the symptoms of a
cancer one already have.
Prevention of Cancer

Prevention of Cancer…
A. Primary Prevention:
1. Make appropriate lifestyle changes.
2. Stop smoking.
3. Limit alcohol intake.
4. Eat a healthy diet:
a. Use the Food Pyramid as a guideline and eat a
variety of foods with an emphasis on plant
resources.
b. Eat five or more servings of a variety of
vegetables and fruits daily.

c. Choose whole grains over refined grains.
d. Reduce dietary fat and preservatives, including
smoked and salt-cured meats containing high
nitrite concentrations.
e. Limit consumption of processed and red meats,
especially high-fat and processed meats.
f. Maintain a healthful weight with body mass index
between 18 and 25.
g. Limit alcoholic beverages to no more than 2
drinks per day for men and 1 drink per day for
women.
Prevention…

5. Be physically active: maintain a healthy weight
and follow exercise guidelines:
a. Adults should engage in moderate to vigorous
physical activity (separate from usual activity)
for 30 minutes on 5 or more days of the week;
however, 45 to 60 minutes of intentional activity
is preferable.
b. Children and adolescents should engage in 60
minutes per day of moderate to vigorous
physical activity at least 5 days per week.
Prevention…

6. Obtain adequate, consistent periods of rest (at
least 6 to 8 hours per night).
7. Avoid sun exposure, especially during the hours of
10 A.M. and 4 P.M. and cover exposed skin with
sunscreen with a skin protection factor of 15 or
higher.
8. Those at high risk for certain cancers should
consider genetic counseling and testing.
9. Chemoprevention:
a. Aspirin—low-dose aspirin may reduce risk colon
cancer in patient with a history of polyps.
Prevention…

b. Tamoxifen and Raloxifene—can reduce the
risk of breast cancer in women who are at
high risk by nearly 50%.
c. Finasteride—may reduce the risk of prostate
cancer.
d. COX-2 inhibitors—may reduce the risk of GI
cancers.
e. Vitamin D—may play a role in reducing the
risk of breast cancer.
f. Statins—may reduce colon, breast, and
hematologic malignancies.
Prevention…

g. Lung cancer — At present, no organization
recommends testing for early lung cancer
detection in asymptomatic individuals. However,
the ACS has recognized that patients at high risk,
due to significant exposure to tobacco smoke or
occupational exposure, may decide to undergo
testing for early lung cancer detection—a decision
that should be made upon consultation with their
physicians.
Prevention…

h. Cervical cancer: screening should begin about
3 years after a woman begins having vaginal
intercourse, but no later than age 21.
Women age 70 who have had three or more
normal Pap tests and no abnormal Pap tests in
the last 10 years and women who have had a
total hysterectomy may choose to stop cervical
cancer screening.
Visual inspection with acetic acid (VIA) for cervical
cancer in low-resource settings.
Prevention…

9. Eliminate, reduce, or change the perception of
stressors and enhance the ability to effectively
cope with stressors
10. Vaccinations— Vaccine hepatitis B virus (HBV).
HPV is now known to cause about 70% of cervical
cancer. The ACS has established guidelines on the
use of this vaccine.
a. Routine HPV vaccination is recommended for
females ages 11 to 12.
b. Females as young as age 9 may receive HPV
vaccination.
Prevention…

c. HPV vaccination is also recommended for
females ages 13 to 18 to “catch up” missed
doses of the vaccine or complete the
vaccination series.
d. HPV vaccination is not currently
recommended for women over age 26 or for
males.
e. Screening for cervical cancer should continue
in both vaccinated and unvaccinated women.
Prevention…

B. Secondary Prevention
Screening and early detection to improve overall
outcome and survival:
1. Performing routine screening tests.
2. Screening should be based on an individual’s age,
sex, family history of cancer, ethnic group or race,
previous iatrogenic factors (prior radiation
therapy or drugs such as DES), and history of
exposure to environmental carcinogens.
Prevention…

a. Prostate cancer: The ACS recommends an
annual prostate specific antigen (PSA) and
digital rectal examination for men over age 50.
The American Urological Association also
recommends annual testing for men age 40
and over who are at high risk (black race,
family history of prostate cancer).
Prevention…

b. Breast cancer: The ACS recommends a clinical
breast examination every 3 years from ages 20 to
39 and annually thereafter. Mammography
should begin at age 40.
c. Colon cancer: begin for all men and women
over age 50. Patients should be screened with
yearly fecal occult blood test, sigmoidoscopy
every 5 years, double contrast barium enema
every 5 years, or colonoscopy every 10 years.
Prevention…

Summary

References
• Smeltzer SC, Bare BG, Hinkle JL, Cheever KH. Brunner & Suddharth’s
Textbook of Medical- Surgical Nursing, 11th Edition. Volume 2. New Delhi;
Wolters Kluwer (India). Pvt.Ltd.
• Weinstein L, Stuart T. Orthopaedics Principle and their Applications. JB
lippincott .5th edition.
• Maheshwari & Mhaskar. Essential Orthopaedics. 5th edition. Knee &
shoulder Clinic ( New Delhi).
• Black JM, Hawks JH. . Medical –Surgical Nursing.8th edition. Volume 1. New
Delhi; Elesiver, 2010.
• Basavanthapa BT. Handbook of Medical Surgical Nursing. Jaypee Brothers
Medical Publishers (P) Ltd. 4th Edition.

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Cancer Pathogenesis, Warning Signs and Prevention

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