Chapter 3Cancer

• Cancer is a condition of uncontrolled cellular proliferation that knows no limits and serves no purpose for the host. The term cancer refers to more than 100 forms of the disease.

• For a cell to become cancerous, the following genetic alterations must occur :

- spur cell growth; - inactivate genes that normally slow growth; - cells keep dividing, - cells live on with abnormalities (no apoptosis). - recruit normal cells to support and nourish them. - develop strategies that prevent the immune system

from destroying them.

Physiologic Concepts1-Cellular Differentiation - Normal cells differentiate during

development. - Differentiation means that a given cell

becomes specialized in structure and function. For example, some embryonic cells are destined to become cells of the retina, whereas others are destined to become cells of the skin or heart.

The more highly differentiated a cell, the less frequently it will go through the cell cycle to reproduce and divide.

- Neural cells, which do not reproduce, are highly differentiated cells.

- Cells that seldom or never go through the cell cycle are unlikely to become cancerous, while cells that go through the cell cycle frequently are more likely to become so.

2-The Cell Clock Normal human cells reproduce a predictable

number of times, after which they stop . This implies that cells possess some counting system that tells them when to stop dividing.

This system is important because if cells divided indefinitely we would have many more cells than is compatible with life.

Pathophysiologic ConceptsUncontrolled Cellular Reproduction• Cancer cells go through the cell cycle more often

than normal, resulting in an overabundance of abnormal cells. Cancer cells spend little time in the gap stages of interphase .

• Uncontrolled cellular reproduction occurs when cells become independent of normal growth control signals. This characteristic of cancer cells is called autonomy. Autonomy results when cells do not respond to growth inhibitors released by neighboring cells or inhibitory growth factors and hormones traveling in the circulation.

AnaplasiaAnaplasia refers to regression of a differentiated

cell to a less differentiated stage. Cancer cells demonstrate various degrees of anaplasia. By undergoing anaplasia, a cancer cell loses its ability to perform its previous functions and bears little resemblance to its tissue of origin. Highly anaplastic cells may appear embryonic and begin to express functions of a different cellular type. Some cancer cells may become ectopic sites of hormone production. For instance, antidiuretic hormone (ADH) or adrenocorticotrophic hormone (ACTH).

Tumor Cell MarkersSome cancer cells release specific substances into the

blood, urine, or spinal fluid called tumor cell markers .

Clinical Implications of Tumor Cell Markers1-They offer a means of identifying certain cancers,

for instance, if a specific tumor cell marker is identified in a patient, it suggests that cancer may exist in the person, and further diagnostic

evaluation is necessary .

2- Detects cancer's progression before, during, and after treatment.

-If after radiation or chemotherapy the tumor cell marker is not detectable, it suggests that the cancer is in remission.

-If the tumor cell marker fails to decrease during therapy or reappears in high concentration after therapy, the tumor is unlikely to be in remission.

Examples of Tumor Cell Markers• Alpha-fetoprotein for liver ,ovarian and testicular

cancers.• Carcinoembryonic antigen for colorectal cancer• Human chorionic gonadotropin (hCG) for many

tumors, including usually cancer of the uterus• Acid phosphatase and prostate-specific antigen

(PSA) for prostate cancer• CA-125 is a marker for ovarian cancer.• N.B., Failure to detect a tumor cell marker does

not mean that an individual is cancer-free.

Factors that affect tumor Growth Rate• person's age, sex, and overall health and

nutritional status. • The status of the host's immune system is also

important. An individual who is immunosuppressed may be unable to recognize a tumor as foreign.

• Certain hormonal states (e.g., pregnancy) may stimulate certain tumor growth rates.

• stress may affect the host's ability to restrict the development or growth of a tumor.

• location in the body and its blood supply. • The degree of cellular anaplasia and the

presence or absence of tumor growth factors are also important.

Descriptions of Tumor Growth and Spread Grading: is histologic assessment of the

tumor based on the degree of anaplasia it demonstrates. For example, poorly differentiated (highly anaplastic) cells are assigned a high grade.

• Staging: A clinical decision concerning the size of a tumor, the degree of local invasion, and the degree to which it has spread to distant sites in a given individual.

Local Growth of a TumorGrowing tumors kill neighboring cells by:- compressing the cells - blocking off their blood supply. - Releasing chemicals or enzymes that cause the

neighboring cells to lyse and die. When neighboring cells die, the tumor can easily grow to occupy that space.

*To grow beyond a certain size, tumors must stimulate the development of their own blood supply( angiogenesis) to meet high metabolic demands.

Metastasis Is the movement of cancer cells from one part of the

body to another. Metastasis usually occurs through the spread of

cancer cells from the original (primary) site in the blood or lymph to a new, secondary site.

The term malignancy refers to the ability of a tumor to metastasize.

Process of MetastasisSteps involved in the metastasis of a primary tumor to a

distant site include :1-DetachmentCancer cells must first detach from their primary cluster. ----

Normal cells detach with difficulty and if it has become detached from its neighbors, it undergoes apoptosis.

-Cancer cells, in contrast, easily detach and begin to enter the circulation.

2- InvasionDetached tumor cells must gain entrance to a blood or lymph vessel by secreting specific enzymes that attack the integrity of the tissue.

3-Dissemination and Seeding Movement of tumor cells in the blood or lymph is

called dissemination. Some tumor cells will get caught in a capillary or lymph ,many cells may die, a few tumor cells at this new site may survive and begin to seed the area and start a new tumor growth.

When the secondary site has reached a critical size, the tumor cells will again begin to produce tumor angiogenesis factor and new blood vessel formation will be initiated to support growth of this secondary site.

Progress of a Metastasizing Tumor -The lungs, which receive systemic venous blood, are

the most common sites of metastasis. - Liver is the most common site of cancers from GIT and

pancreas. N. B., Metastasis is evaluated by observing for secondary

sites in the lymph nodes nearest to the primary site, and then progressively further from this site.

Exceptions to this rule are tumor cells that show a striking preference to colonize certain tissues not necessarily downstream. The classic example of this preference is the tendency of prostate cancer to metastasize to bone

The Immune System and Cancerthe immune and inflammatory systems have

important roles in fighting and preventing cancer as:

-Antibodies, T cells, and natural killer (NK) cells has been confirmed in individuals with cancer.

-Individuals who are immunocompromised, including those with AIDS or those taking immunosuppressant drugs, have an increased chance of developing cancer.

Categories of Cancer The suffix oma is usually added to the tissue term .• Carcinoma is a cancer of the epithelial tissue,

including cells of the skin, glands, breast, cervix, colon, rectum, stomach, pancreas, and esophagus.

• Lymphoma is a cancer of the lymphatic tissuehi. • Sarcoma is a cancer of the connective tissue,

including cells found in the muscle and bone.• Glioma is a cancer of the glial (support) cells of the

central nervous system.• Carcinoma in situ describes abnormal epithelial

cells that are as yet confined to a certain area and thus considered preinvasive lesions.

The Theory of Carcinogenesis -Cancer development is a multi-step process that

usually requires decades to occur. 1 -The first step is mutation in the DNA during

replication . If a mistake cannot be repaired by enzymes, the cell normally is instructed to self-destruct.

If the DNA error is not corrected or no self-destruction occur, the genetic change becomes a permanent mutation and is passed on to all daughter cells. This step is irreversible and is called cellular initiation

2 -The second step is promoting events : interactions with endogenous and exogenous (environmental) factors that cause additional genetic changes leading the cell to proliferates

aggressively and without quality control .

Factors that promote the acceleration of the cell cycle and those that allow an abnormal cell to avoid detection by the immune system are most likely to result in a mutated cell becoming carcinogenic.

Promoters of DNA Replication Errors - Certain physical agents and chemicals agents as

ionizing radiation, ultraviolet radiation, components of cigarette smoke, aromatic hydrocarbons, certain dyes, nitrosamines (present in preserved meats), and asbestos.

- Certain viruses have been identified that can cause DNA mutations as Burkitt's lymphoma, caused by the Epstein-Barr virus, cervical cancer, caused by certain strains of the human papilloma virus, and liver cancer, caused by the hepatitis B virus. Kaposi's sarcoma occurs especially in those suffering from AIDS.

Risk Factors for cancer1-Exposure to any physical, chemical, or viral

substance that is known to be mutagenic, and prolonged exposure to any promoter.

2-Behavioral Risk Factors include : - cigarette smoking and diets rich in animal fat

and preserved meats. - exposure to asbestos, coal tar and radiation

from sunlight. - sexual behavior

3- Hormonal Risk Factors - Estrogen may act as a promoter for certain

cancers, such as breast and endometrial cancer. Because estrogen levels are high in menstruating women, the risk for developing breast cancer is increased in women who started menstruating early and reached menopause late.

4- Inherited Risk Factors Certain cancers have a higher tendency to

run in families than others. For example, colon and breast cancer .

Protective Factors Against Cancer Development -Women who breastfeed for at least 6 consecutive

months and who have had multiple pregnancies have a reduced risk of breast cancer.

- Progesterone appears to be protective against breast cancer by inhibiting the stimulatory effects of estrogen. Progesterone is high during pregnancy, which may explain why women who have had many pregnancies have a reduced risk of breast cancer. - Vitamins A, E, and C and folic acid, are important in reducing cancer risk. All of which are prevalent in green, leafy and colorful vegetables and fruits.

Clinical Manifestations of cancer-Cachexia is the general wasting of fat and protein.- Anemia.- Fatigue as a result of poor nutrition, and poor oxygenation of tissues resulting from anemia..

Diagnostic Tools• Screening tests, such as Pap smears to detect

cervical cancer, mammograms to detect breast cancer, and digital examinations of the prostate.

• Blood assay for prostate-specific antigen (PSA) and other cancer markers may be performed based on suspicion.

• Advanced methods include radiographs, CAT scans, and magnetic resonance imaging (MRI). Special bone scans may also be used.

• Cancer diagnosis is confirmed by surgically extracting a sample from a suspicious lesion, a procedure known as a biopsy, and performing a microscopic examination of the cells.

Complications - Infections develop as a result of protein malnutrition, and immune suppression . - Pain may result of the invading tumor pressing on nerves or blood vessels specially in space-limiting compartments, such as bone or brain. - Compression of the blood vessels can lead to tissue hypoxia, lactic acid accumulation, or cell death.-Headache is a common manifestation of advanced brain cancer.- bone pain is common with bone cancer at any age. - GI pain occurs when the smooth muscle of the gut is stretched.

Treatment I-Surgery has a better chance of curing a cancer if

used on solid, well-circumscribed tumors. -It may be used to relief pain or to debulk the

tumor, which reduces burden and improves the response to chemotherapy or radiotherapy.

II-Radiation therapy uses ionizing radiation to kill cells primarily by altering the DNA enough that brakes on the cell cycle. Often, radiation is used in addition to surgery to shrink the tumor.

III-Chemotherapy uses drugs to destroy tumors which grow rapidly (most susceptible to chemotherapy).

• However, healthy cells are also susceptible to the damaging effects of chemotherapy.

• Chemotherapy is frequently used in addition to surgery or radiation therapy, but may be used alone. It also may be used for palliative purposes.

• Chemotherapy usually causes bone marrow suppression, which in turn causes fatigue, anemia, bleeding tendencies, and an increased risk of infection.

IV-Immunotherapy is a form of cancer treatment that takes advantage of the two cardinal features of the

immune system: specificity and memory .-Immunotherapy may stimulate the host's own

immune system to respond more aggressively to a tumor ,

-or tumor cells may be attacked by antibodies developed in the laboratory

Cancer Prevention - Avoidance of cigarette smoking - A diet rich in fruits, vegetables, and fiber

and low in animal fat . - Avoidance of sexually transmitted diseasesCancer Detection• Early cancer detection tests include self breast

examination and mammography, prostate examination, self testicular examination, and regular skin examination.

• Some screening tests, including Pap smears, tests for intestinal polyps, and biopsies of abnormal skin lesions.