CANCER BIOLOGY and CHEMOTHERAPY

8/6/2019 CANCER BIOLOGY and CHEMOTHERAPY

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CANCER BIOLOGY & CHEMOTHERAPYPrepared by

Dennis N. Muoz, P.T.R.P., R.N., R.M.

2. Please highlight the concepts tackled frommodules 1-3 related to your answers.MODULE 1: Adaptive and Regulatory Mechanism

y Homeostasis & Constancyy Negative feedback Mechanismy Adaptive Mechanisms and Stress Responsey Importance ofIntrinsic and Extrinsic Factors in Adaptation and Disease Causation

MODULE 2: Cellular Functions (Overview)y Cell Cycle Periodsy How cells are Organized

Module 3: Alterations in Protective Mechanism: Inflammation and Infectiony Cellular and Vascular Responses to Inflammation

INTRODUCTION TO CANCER BIOLOGY

Cancer is the third leading cause of morbidity and mortality in the Philippines. Leading

cancer sites/types are lung, breast, cervix, liver, colon and rectum, prostate, stomach, oral cavity,

ovary and leukemia. There is at present a low cancer prevention consciousness and most cancer

patients seek consultation only at advanced stages. Cancer survival rates are relatively low

(Ngelangel & Wang, 2001).

Cancer is a term used for diseases in which abnormal cells divide without control and are

able to invade other tissues. Cancer cells can spread to other parts of the body through the blood

and lymph systems. Cancer is not just one disease but many diseases. There are more than 100

different types of cancer (National Cancer Institute, Retrieved 2011).

The term cancer covers a number of diseases in which the growth of cells becomes

uncontrolled. Cancer cells fail to respond to the usual controlling signals and their growth

becomes unregulated. Indeed, the name cancercomes from a Latin word meaning a crab, and

describes the manner in which the pattern of penetration into normal tissues by the abnormal

growth bears a superficial resemblance to a crabs claw (Ahmed, 2007).

Cancer is a genetic disease. The malignant phenotype often requires mutations in several

different genes. Cancer cells generally retain the capacity to proliferate by acquiring mutations in

cell cycle regulatory genes (particularly those regulating the G1 checkpoint). Often

mutationsactivate cell pathways leading to proliferation and block pathways of differentiation.

The normal cell has protective mechanisms that lead to the repair of cell damage; these repair

pathways are often abnormal in cancer cells. When a normal cell has sustained too much damage

to repair, the cell activates a suicide pathway to prevent damage to the organ. These cell death

pathways are also commonly altered in cancer cells, leading to the survival of damaged cells that

would normally die (Kasper , D. L. et al,2005).


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The causes of cancer are complex and varied. Some arise from environmental agents called

carcinogens, others are brought about by oncogenic, and that is cancer-inducing, viruses. Most

cancers arise, ultimately, from mutations in DNA. These mutations may be caused by

environmental agents, or may be inherited in the germ line, making individuals more susceptible

to cancer Ahmed, 2007).

Ahmed (2007) further stated that Germline DNA refers to the DNA which is present in the

cells that give rise to the gametes, that is, the sperm and eggs. The egg and sperm fuse to form a

zygote, and, as further divisions occur, that DNA is passed to all the cells in the developing

embryo. Mutations which occur in germline DNA are present in the gametes and in all the cells of

the individuals to which they give rise See figure1.

Figure 1. Acquired mutations develop in DNA during a persons lifetime. If the mutation arises in a body cell, copies of themutation will exist only in the descendants of that particular cell. From the National Institutes of Health and National Cancer

Institute. (1995). Understanding gene testing (NIH Pub. No. 96-3905). Washington, DC: U.S. Department of Human Services

(Smeltzer & Bare, Medical Surgical Nursing, 2004, pp.129).

Treatment options offered to cancer patients should be based on realistic and achievable

goals for each specific type of cancer. The range of possible treatment goals may include complete

eradication of malignant disease (cure), prolonged survival and containment of cancer cell growth

(control), or relief of symptoms associated with the disease (palliation) (Smeltzer and Bare, 2004).

3. Present a textual explanation or paradigm for itThe normal Cell Cycle

Somatic cells proliferate by mitosis, a process that produces two identical progeny from one

parental cell. Mitotic cells pass through an ordered series of states collectively termed the 'cell

cycle. See Figure 2.


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Figure 2. Cell cycle. The sequential phases of the cell cycle, G 1, S, G2, and M, are depicted, as well as the resting G 0

phase. Common regulatory points near the end of G1 and between G1 and G0 are shown by circles with arrows

within.

This cycle has four sequential phases, labelled G 1, S, G2, and M, which are defined biochemically,

morphologically, and on the basis of cellular DNA content.

G1 and G2 phases were originally conceived as 'gaps' between the distinctive M and S phases of

the cell cycle.

G 1 is the period between M and S when cells are 2N, have finished one round of cell division, and

have not yet initiated the next.

G1 is the period of cell growth, and a certain increase in mass may be required before the cell can

enter the next S phase. When conditions are unsuitable for cell proliferation, they arrest in G 1,

and those that are already in S, G2, or M usually complete the round they have entered and arrest

only when they reach G 1 again. A point in late G 1 called the 'restriction point' or 'R' has special

significance and is the point past which cells become committed to enter S, even if mitogens are

withdrawn. Cells may withdraw from the cell cycle and remain for prolonged periods in a

metabolically active but non-proliferative state.

These cells have 2N DNA content and are described as being in G 0. Terminally differentiated

cells are examples of cells in G0. However, other cells reversibly enter G 0 and may be induced to

return to G1 and begin cycling again under certain conditions (distinction between cells in G0

and prolonged G1, admittedly, may be difficult).

EXAMPLE Hepatocytes are in G 0 unless partial hepatectomy or hepatotoxic insults induce them

to proliferate to reconstitute functional liver mass. Resting, antigen-specific lymphocytes remain in

G 0 until antigen and cytokine stimulation induces them to proliferate.

S phase is the period of wholesale DNA synthesis during which the parental diploid cell with a '2N'

complement of DNA replicates its entire genetic content and becomes a cell with 4N DNA content.


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The durations of S, G2, and M tend to be relatively constant, in contrast to that ofG 1 which can

be highly variable depending on the cell type and is subject to regulation by environmental

factors, such as the availability ofmitogens and nutrients.

G 2 is the period between S and M, when cells have finished replicating their DNA, have 4N DNA,

and are preparing to divide.

M phase or mitosis is the period of nuclear and cell division during which the duplicated DNA

complement of the 4N parental cell is divided equally between the two progeny cells which are

consequently 2N.

M phase is morphologically obvious as the period during which chromosomes condense into their

familiar, microscopically visible forms, the nuclear envelope breaks down, the chromosomes

segregate into two identical sets, the nuclear envelopes reforms (which completes nuclear division

or 'karyokinesis'), and the two progeny cells separate (which completes cell division or

'cytokinesis').

Adherence to the G1SG2M sequence during normal progression through the cell cycle means

that a cell must duplicate its DNA before dividing and that it must divide before duplicating its

DNA again. This insures a normal genetic complement in the progeny cells and maintains genetic

constancy. The dependence of later events in the cell cycle upon normal completion of earlier

events is insured by 'checkpoint' control mechanisms that prevent a cell that has not successfully

completed one phase of the cycle from entering the next. Checkpoint activity is seen after cell

exposure to DNA-damaging agents, such as ionizing radiation, and is manifest as delayed cell entry

into S and M by inducing temporary arrest in G 1 or G2. This delay allows cells time either to repair

its damaged DNA or, if the damage is irreparable, to execute a programme of self-destruction or

apoptosis.

According to Guyton( 2006) The major differences between the cancer cell and the normal cell

are the following:

(1)The cancer cell does not respect usual cellular growth limits; the reason for this is that

these cells presumably do not require all the same growth factors that are necessary to

cause growth of normal cells.

(2)Cancer cells often are far less adhesive to one another than are normal cells. Therefore,

they have a tendency to wander through the tissues, to enter the blood stream, and to be

transported all through the body, where they form nidi for numerous new cancerous

growths.(3)Some cancers also produce angiogenic factors that cause many new blood vessels to grow

into the cancer, thus supplying the nutrients required for cancer growth. See Table 1 for

further comparison between Normal and Cancer Cells.

Table 1 Represents Detailed Comparison Between Cancer Cells and Normal Cells


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Table 2 SUMMARY OF THE PHENOTYPIC CHANGES IN THE PROGRESSION OF

NEOPLASIA. (CHANCER CHARACTERISTICS) ACCORDING TO GANONG (2007)

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Why Do Cancer Cells Kill?

Guytong (2006) stated that cancer tissue competes with normal tissues for nutrients why

patients died of cancer. Because cancer cells continue to proliferate indefinitely, their number

multiplying day by day, cancer cells soon demand essentially all the nutrition available to the

body or to an essential part of the body. As a result, normal tissues gradually suffer nutritive

death.


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Cancer Developmentin Molecular Perspective

Normally, cells in a differentiated state are stimulated to enter the cell cycle from a quiescent state, or G0,

or continue after completion of a prior cell division cycle in response to environmental cues including

growth factor and hormonal signals. Cells progress through G1 and enter S-phase after passing throughcheckpoints, which are biochemically regulated transition points, to assure that the genome is ready

for replication. The cyclin-dependent kinases (CDKs) are enzymes that critically regulate cell cycle

progression from one phase to the next. One important checkpoint is mediated by the p53 tumor-

suppressor gene product, acting through its upregulation of the p21WAF1 inhibitor of CDK function, acting

on CDKs 4 or 6. These kinase molecules can also be inhibited by the p16INK4A and p27KIP1 CDK inhibitors,

but in turn are activated by cyclins of the D family (which appear during G1) and the proper sequence of

regulatory phosphorylations, See Figure 4. (Kasper , D. L. et al., 2005).

Activated CDKs 4 or 6 phosphorylate, and thus inactivate, the product of the retinoblastoma susceptibility

gene, pRb, which in its nonphosphorylated state complexes with transcription factors of the E2F family.

Phosphorylated pRbreleases E2Fs, which activate genes important in completing DNA replication during S-

phase, progression through which is promoted by CDK2 acting in concert with cylins A and E. During G2,

another checkpoint occurs, in which the cell assures the completion of correct DNA synthesis. Cells then

progress into M-phase under the influence of CDK1 and cyclin B. Cells may then go on to a subsequent

division cycle or enter into a quiescent, differentiated state (Kasper , D. L. et al. , 2005).

Also shown in Fig. 3 are the sites of action of protooncogenes, regulators of cellular proliferation that, in an

active state, promote cell growth, and whose deregulation produces oncogenes, originally discovered as

the genes encoded by tumor-forming viruses in animals.

Oncogenes can be divided into two families: (1) those that act in the cytoplasm to disrupt normal growth

factorrelated signaling, including ras, raf, and the tyrosine kinases of the src and erbB or sis families; and

(2) nuclear oncogenes, includingjun,fos, myc, and myb, that act to alter transcriptional control of cassettesof genes. In contrast, tumorsuppressor genes, including p53and pRb, act as cellular brakes (Kasper , D. L.

et al. , 2005)

70 Principles of Cancer Treatment 469


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Figure 3. The sites of action of protooncogenes, regulators of cellular proliferation that, in an active state, promote

cell growth, and whose deregulation produces oncogenes, originally discovered as the genes encoded by tumor-

forming viruses in animals.

Figure 4. Proliferation of the Cancer Cell


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Chemotherapy

A knowledge of cancer chemotherapy requires an appreciation of some general principles of

tumour biology. Cancer results from the uninhibited growth of a single clone of cells. As cancer cells grow,

they move through the cell cycle, characterized by several phases: resting (G0), pre-DNA synthesis (G1),DNA synthesis (S), post-DNA synthesis (G2), mitosis (M). Most chemotherapy drugs are active in the S

phase of the cell cycle, although some directly block cells entering mitosis and most directly promote

apoptosis (programmed cell death).

RATINALE OF CHEMOTHERAPY IN CANCER TREATMENT

1. Foremost, chemotherapy is applied as primary therapy for the treatment of advanced-stage cancer.

A few diseases, including leukaemias, lymphomas, and advanced-stage germ cell tumours are

sensitive to multiple chemotherapy agents and can be cured with combination chemotherapy.

More often, combinations of therapeutic agents are used to diminish tumour-related symptoms,

improve the quality of life, and extend survival in patients with advanced-stage tumours. For

example randomized clinical trials of chemotherapy versus best supportive care havedemonstrated a survival advantage and quality of life improvement when patients with advanced-

stage lung cancer receive chemotherapy.

2. Second, chemotherapy can be used as neoadjuvant therapy, given prior to radiation or surgery for

locally advanced disease. In this setting, the drugs are used to decrease the tumour mass, reduce

the extent of the subsequent surgery or radiation, and to determine disease sensitivity to drugs.

Clinical trials have identified a potential role for neoadjuvant therapy in the treatment of lung

cancer, oesophageal cancer, and locally advanced breast cancer, among other diseases. In the case

of osteosarcomas, neoadjuvant therapy can provide important information about tumour

sensitivity, thereby permitting a more tailored approach to further management.

3. Finally, the drugs can be used as adjuvant therapy, administered after the completion of local

definitive surgery and/or radiation therapy in order to decrease the risk of recurrence. For instance

adjuvant chemotherapy reduces the risk of tumour recurrence and improves survival in node-

positive colon cancer and in breast cancer following surgical resection. In all of these settings,

chemotherapy can be administered in conjunction with radiation therapy to optimize local effects

of treatment.

Classes of chemotherapy agents

Agents could be categorized (Refer to Fig. 5 and Figure 6) as:

1. cell cycleactive, phasespecific (e.g., antimetabolites, purines, and pyrimidines in S-phase; vinca

alkaloids in M), and

2. phase-nonspecific agents [e.g., alkylators, and antitumor antibiotics including the anthracyclines,

dactinomycin (formerly actinomycin D), and mitomycin], which can injure DNA at any phase of the

cell cycle but appear to then block in S-phase or G2 at a checkpoint in the cell cycle before cell

division.

Cells arrested at a checkpoint may repair DNA lesions. Checkpoints have been defined at the G1 to S

transition, mediated by the tumor-suppressor gene p53(giving rise to the characterization ofp53as a

guardian of the genome); at the G2 to M transition, mediated by the chk1 kinase and additional p53-

related pathways influencing the function of CDK1; and during M-phase, to ensure the integrity of the

mitotic spindle (Kasper , D. L. et al. , 2005).


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Cell Cycle

Cell Cycle SpecificAgents

Antimetabolites

Bleomycin

PodophyllinAlkaloids

Plant Alkaloids

Cell Cycle Non-Specific

Agents

Alkylating Agents

Antibiotics

Cisplatin Nitrosoureas

Figure 5. Cell Cycle Specific and Non-Specific Agents

Figure 6. Classification of Cytotoxic Drugs

The importance of the concept of checkpoints extends from the hypothesis that repair of

chemotherapy-mediated damage can occur while cells are stopped at a checkpoint; therefore,

manipulation of checkpoint function emerges as an important basis of affecting resistance to

chemotherapeutic agents. See Figure 7, 8 and Cancer Resistance Figure 9.


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Antibioti

Anti

etabolite

S

(2-6h)G2

(2-32h)

M

(0.5-2h)

Alkylating agent

G1

(2-gh)

G0

Vin

a alkaloid

Mitoti inhibitor

Taxoid

Action sites of cytotoxicagents: Cell cycle level

Figure 7: Action Sites of Cytotoxic Agent at cell cycle level

There are several distinct classes of chemotherapy agents . Because these drugs can have major side-

effects, only physicians knowledgeable in their dosing and side-effects should administer them. In order

to reduce variability in exposure to drugs, doses of most chemotherapy agents are administered based

on the patient's body surface area, a calculation determined by the patient's height and weight. In

addition, doses of chemotherapy need to be adjusted for renal (methotrexate, bleomycin,

fludarabine) and hepatic function (anthracyclines, vinca alkaloids, taxanes). Adequate intravenous

access must be secured since many of the drugs are vesicants and extravasation can lead to tissue

necrosis. Similarly, patients must be adequately hydrated prior to the administration of cisplatin and

cyclophosphamide, to prevent renal toxicity and bladder toxicity, respectively. Careful attention must

be given to fluid and electrolyte balance with the administration of many agents. Cisplatin renal toxicity

can cause profound hypomagnesaemia.

y Antimetabolites exert their cytotoxicity by serving as substrates in pathways vital to cellular function

and replication. Many of these agents are incorporated into DNA or RNA or act on enzymes involved in

the synthesis of nucleic acids. Methotrexate acts by inhibiting the enzyme dihydrofolate reductase,which maintains intracellular pools of reduced tetrahydrofolates required for the synthesis of purine

nucleotides and thymidylate.

y 5-Fluorouricil is another commonly used antimetabolite. A metabolite of this drug, fluorodeoxyuridine

monophospate inhibits thymidylate synthase, an enzyme required for the synthesis of deoxythymidine

triphosphate and DNA. In addition, fluorodeoxyuridine triphosphate is incorporated into RNA,

interfering with its function, and fluorodeoxyuridine triphosphate is incorporated into DNA, leading to

strand breakage.

y A third important antimetabolite is cytarabine (ara-C) which is converted to cytarabine triphosphate

(ara-CTP) in the cell. Cytarabine triphosphate is incorporated into DNA and serves as a chainterminator. A related deoxycytidine analogue, gemcitabine, has the additional actions of inhibiting the

conversion of ribonucleotides to deoxyribonucleotides, which are DNA precursors. Prolonged exposure

of tumour cells to some of the antimetabolites, such as 5-fluorouracil and cytosine arabinoside,

through continuous intravenous infusion may be more effective than bolus injections alone.


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y Purine analogues also have important roles as antimetabolites; 6-mercaptopurinre (6-MP) and 6-

thioguanine (6-TG) are converted in the cell to monophosphates which inhibit the first step of purine

synthesis.

y Moreover, the triphosphate nucleotides of 6-mercaptopurinre and 6-thioguanine are incorporated into

DNA resulting in an increase in strand breaks. Another purine analogue is fludarabine phosphate, which

serves as an adenosine analogue. Fludarabine is converted to 2-fluoro-ara-A in plasma and

subsequently is phosphorylated intracellularly. The resulting triphosphate inhibits DNA polymerase and

ribonucleotide reductase, interfering with DNA and RNA synthesis.

y Alkylating agents exert their cytotoxicity by binding to DNA and forming DNA adducts which alter DNA

structure and function enough to disrupt DNA replication and transcription. They act throughout the

cell cycle, but have their greatest activity on rapidly proliferating cells. These agents, including

cyclophosphamide, nitrogen mustard, melphalan, busulfan, and chlorambucil were among the first

chemotherapy drugs and remain important agents in cancer therapy, with particular activity in

haematological malignancies and breast cancer. In a similar manner, the platinum derivatives bind to

and cross-link DNA, leading to DNA breaks and apoptosis.

y The anthracyclines intercalate into DNA and disrupt DNA synthesis. The antitumour activity of

doxorubicin and daunorubicin, the two most commonly used agents in this drug class, results in part

from triggering of topoisomerase II dependent DNA breaks. Etoposide also inhibits topoisomerase II. In

a similar way, other topoisomerase inhibitors interfere with topoisomerase I, which is critical in the

repair of normal DNA; these agents include irinotecan and topotecan. Vinca alkaloids interfere with

microtubule formation and disrupt cell division. In contrast, the taxanes stabilize microtubule assembly,

also inhibiting mitosis.

y Along with the traditional cytotoxic agents, hormone-directed therapy can be critical in the regulation

of tumours. The growth of many normal tissues and tumours is influenced by hormone exposure. Many

breast cancers express receptors for oestrogen and progesterone and most prostate cancers haveandrogen receptors. Depriving these tumours of the hormonal stimulus can exert both cytocidal and

cytostatic effects on the cell. Thus, more than 50 per cent of breast cancers expressing the oestrogen

receptor will respond to treatment with tamoxifen, an antioestrogen. Similarly, the use of luteinizing

hormone releasing hormone (LHRH) agonists (which reduce testosterone synthesis) or antiandrogens

can have dramatic effects on prostate cancer growth.


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Action sites of cytotoxic

agents: Cellular levelDNA synthesis

Anti t lit s

D A

D A tr nscri ti n D A duplic ti n

Mit sis

Al l ting agents

pindle poisons

Intercalating agents

Figure 8 Cytotoxic Agent at Cellular Level

EXTRACELLULAR INTRACELLULAR

ATP

PGP170 ATP

Drug

Drug

PlasmaMembra e

ONCOLOGYPri ciples chem herapyDrug resis a ce


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Figure 9 This phosphoglycoprotein (P.G.P.) is responsible for multidrug resistance. It acts by

rejecting the anticancer agent from the cell. Other mechanisms of resistance exist.

The Synopsis of Chemotherapeutic Drugs and the Mechanism of Action explained in Table 9-20


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Detailed Action sites of cytotoxic agents

during the course of cancer proliferation

6-MERCAPTOPURINE

6-THIOGUANINE

METHOTREXATE

5-FLUOROURACIL

HYDROXYUREA

CYTARABINE

PURINE SYNTHESIS PYRIMIDINE SYNTHESIS

RIBONUCLEOTIDES

DEOXYRIBONUCLEOTIDES

DNA

RNA

PROTEINS

MICROTUBULESENZYMES

L-

SP

R

GIN

SE

VINC

LK

LOIDS

T

XOIDS

LKYL

TING

GENTS

NTIBIOTICS

ETOPOSIDE

Figure 9 Detailed Mechanism of Action of the Cytotoxic Drugs.

Alternative Presentation of Specific chemotherapeutic agent during cellular proliferation and biosynthesis.

(See Diagram Below Figure 9)


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4. SCIENTIFIC JOURNAL

1. R f f R f by Kathryn L. Schwertfeger, Wa Xian, Alan M. Kaplan, et al.

The tumor microenvironment, which includes inflammatory cells, vasculature, extracellular

matrix, and fibroblasts, is a critical mediator of neoplastic progression and metastasis. Using

an inducible transgenic mouse model of preneoplastic progression in the mammary gland, we

discovered that activation of inducible fibroblast growth factor receptor-1 (iFGFR1) in the

mammary epithelium rapidly increased the expression of several genes involved in the

inflammatory response. Further analysis revealed that iFGFR1 activation induced recruitment

of macrophages to the epithelium and continued association with the alveolar hyperplasias

that developed following long-term activation. Studies using HC-11 mammary epithelial cells

showed that iFGFR1-induced expression of the macrophage chemoattractant osteopontin was

required for macrophage recruitment in vitro. Finally, conditional depletion of macrophages

inhibited iFGFR1-mediated epithelial cell proliferation and lateral budding. These findings show

that inflammatory cells, specifically macrophages, are critical for mediating early events in an

inducible transgenic mouse model of preneoplastic progression. (Cancer Res 2006; 66(11):

5676-85)

SourceCancer Res 2006;66:5676-5685. J , 2006.

http://cancerres.aacrjournals.org/content/66/11/5676.full.pdf+html, Retrieved June 6, 2011

2.Keeping Out the Bad Guys: Gateway to Cellular Target

TherapyTakanori Kitamura and Makoto M. Taketo

AbstractTumor-stromal interaction is implicated in many stages of tumor development, although it

remains unclear how genetic lesions in tumor cells affect stromal cells. We have recently shown

that inactivation of transforming growth factor-B family signaling within colon cancer epithelium

increases chemokine CC chemokine ligand 9 (CCL9) and promotes recruitment of the matrixmet

alloproteinase (MMP)-expressing stromal cells that carry CC chemokine receptor 1 (CCR1), the

cognate receptor for CCL9. We have further shown that lack of CCR1 prevents the accumulation of

MMP-expressing cells at the invasion front and suppresses tumor invasion. These results provide

the possibility of a novel therapeutic strategy for advanced cancerprevention of the recruitment

of MMPexpressing cells by chemokine receptor antagonist. [Cancer Res 2007;67(21):10099102]

SourceCancer Res

2007;67:10099-10102. v 1, 2007.http://cancerres.aacrjournals.org/content/67/21/10099.full.pdf+html Retrieved June 24, 2011


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5. Please present a script or a scenario on how toexplain this to the following context.

a. Community or individual patient b. StudentsPrevention is better than as they say. But Cancer is

inevitable. It has a double sword effect. You may not know

you have it, since it has been imprinted in our genes, the

oncogenes, the potential cancer precursor. That is why all

living biological entity is a candidate of this monstrous

disease and no one is 100% secure or free from getting outof it. I guess the best way to provide information to

community, patients and students is through health

teachings. Here are the most common health preventive

measures that will somehow decrease the possibility of

acquiring/developing cancer- the health promotion and

prevention.

Primary PreventionThe assessment or reduction of risk factors before the disease occurs:

y Make appropriate lifestyle changes.

y Stop smoking.

y Limit alcohol intake.

y Eat a healthy diet as outlined above.

y

Be physically active: maintain a healthy weight and follow exercise guidelines outlinedabove.

y 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 (SPF) of 15 or higher.

y Those at high risk for certain cancers should consider genetic counseling and testing.

y Chemoprevention.

o Aspirin= low-dose aspirin may reduce risk of breast cancer and colon polyps.

o Tamoxifen=can reduce the risk of breast cancer in women who are at high risk by

nearly 50%.

o Finasteride=reduces risk of prostate cancer.

o COX-2 inhibitors= reduce risk of colorectal cancer in high-risk patients.

o Calcium= may reduce risk of colorectal adenomas.o Beta carotene= may reduce risk of lung cancer in smokers.

Secondary Prevention


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Screening and early detection to improve overall outcome and survival:

y Performing routine screening tests should be based on whether these tests are adequate

to detect a potentially curable cancer in an otherwise asymptomatic person and are also

cost effective.

y Although all major authorities recommend routine screening for certain types of cancer,each has a different opinion on when screening should begin and how often.

y 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.

o Testicular cancer is the most common cancer between ages 20 and 34, the second

most common from ages 35 to 39 and the third most common between ages 15

and 19. There is an increased risk in males with undescended testicles, gonadal

dysgenesis, and Klinefelter's syndrome. There is also an increased risk in men with a

family history of testicular cancer. Although not consistently found to confer a

higher risk, infertility or abnormal semen parameters have been associated with a

higher risk of testicular cancer in some studies. The American Urological Association

(AUA) recommends annual screening beginning at age 15 with monthly testicular

self examinations.

o Prostate cancer occurs more commonly in men over age 60. With more widespread

screening, younger men are being diagnosed in the early stages of the disease. The

ACS and AUA recommend an annual prostate-specific antigen (PSA) and digital

rectal examination for men over age 50. The AUA also recommends annual testing

for men age 40 and over who are at high risk (black race, family history of prostate

cancer).

o Breast cancer is the most common type of cancer in women, and the incidence

increases with age. The ACS recommends a clinical breast examination every 3years from ages 20 to 39 and annually thereafter. Mammography should begin at

age 40.

o Colon cancer screening should begin for all men and women over age 50. Patients

should be screened with yearly fecal occult blood test, or sigmoidoscopy every 5

years, or double contrast barium enema every 5 years, or colonoscopy every 10

years.

o Lung cancer, although common in both men and women who have smoked, is not

routinely screened for because there is no cost-effective method that would detect

cancer early enough to make a difference in outcome.

References

1. Kasper , D. L. et al. (2005). Harrisons Principles of Internal Medicine 16th

Edition. New York.

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