Patho 2009 - Unit 4

Front 1

1. Describe the two mutational routes that result in uncontrolled cellular proliferation.
Pg. 339

Back 1

A. Some event (carcinogenic) causes a chemical change in the cell's DNA. If there is mutation of a gene (one of the two gene copies), the result is a growth-related product thus causing increased proliferation. If there is mutation of both copies of the gene, there is a loss or deactivation of the gene. Because there is deactivation or loss of the tumor suppressor gene (a gene that inhibits cellular growth), there is uncontrolled growth.
B. There are numerous substances (carcinogens) that can cause cellular mutations. These substances can be physical, chemical, or viral (oncogenic viruses).
C. Initiation and promotion (cocarcinogens)- Initiators cause irreversible changes (mutations) in the DNA. The cell at this time is not considered to be cancerous. A substance that acts as a promoter accelerates the process by which the mutated cell becomes cancerous.

Front 2

2. Describe how autonomy and anaplasia define cancer.
Pg. 337

Back 2

Autonomy refers to the cancer cells independence from normal cellular controls and is part of the transformational process.
Anaplasis is the absence of differentiation and means literally without form. Recognized by a loss of organization and a marked increase in nuclear size with evidence of ongoing proliferation. Variable size and shape or pleomorphic.

Front 3

3. State how tumors are graded.
Pg. 334

Back 3

Benign tumors encapsulated and well differentiated - oma. Malignant tumors rapid growth rates and specific microscopic alternations, including loss of differentiation and absence of moraml tissue organization.Lack a capsule and invade blood vessels, lymphatics, and surrounding structures. Carcinomas.

Front 4

4. Discuss the changes cell surfaces go though and their functional importance in cancer.

Back 4

1. Changes in cellular surface and their functional importance
1. Glycolipids and glycoproteins
2. Altered membrane transport or permeability
1. Role of fibronectin
2. Increase in enzyme secretion by cancer cells
3. Altered anchoring junctions and gap

Front 5

5. Explain the role of tumor cell markers in diagnosis and treatment of specific types of cancer.
P 338

Back 5

are substances hormones, enzymes, genes, antigens, antibodies found on tumor plasma membranes and in blood, spinal fluid, or urine. They are used to screen and identify individuals at high risk for cancer, to help diagnose specific types of tumors, and to follow the clinical course of cancer.

Front 6

6. Discuss the initiation-promotion-progression theory of carcinogenesis.
P 354

Back 6

genetic events are the primary basis of carciunogenesis. Mutations in cancer causing genes accumulate with age, causing the increasing risk of cancer with advanced age.
A. Monoclonal
B. Cell Accidents
C. Slow Stages of Cancer
D. Oncogenes and tumor suppressor genes
E. Stem cell or blocked differentiation
F. The role of intercellular communication
G. Initiation - promotion – progression-This theory refers to the tendency of an initial ‘hit’, or mutation (such as ionizing radiation, infection with a oncovirus, etc) being necessary. Promotion is an ongoing irritation which causes increased cell turnover (such as the inflammation caused in hepatitis C). Increased cell turnover causes an increase in the cells with the ‘hit’. Progression refers to when the neoplasm is of sufficient size that it grows independent of the promoter (or other controls in the body).
II. Environmental factors (chemical, radiation, or viruses) and/or genetic factors cause changes in the genetic make-up of the cell. This can lead to two things: the activation of growth promoting gene (oncogene) or the inactivation of the growth inhibiting gene (cancer suppressing agent). There is then an expression of altered gene products or the loss of gene products that are regulatory. The end result is the development of a malignant tumor.

Front 7

7. State the role of the immune system in tumor surveillance.

Back 7

1. The different types of antigens of cancer cell membranes
2. How cancer cells escape the immune system.

Front 8

8. Describe the role of environment, lifestyle, and hormones play in the development of cancer.

Back 8

Read the last part of chapter 11.

Front 9

1. Describe how tumors invade body tissues and organs P 376

Back 9

1. Attachment
2. Degradation
3. Locomotion

Front 10

2. Describe the theory of invasion as stated in the text
P 380

Back 10

Three step theory of invasion includes 1. Tumor cell attachment to the matrix, 2 degredation, 3. Tumor cell locomotion.

Front 11

3. Discuss the clinical manifestations of cancer and the relationship of the physiological effects of cancer to these manifestations
P 385

Back 11

pain, cachexia, anemia, leucopenia, thrombocytompenia, and infection

Front 12

4. Understand the underlying philosophy of the different treatments of cancer. P 389

Back 12

A. Chemotherapy
1. Main types of drugs used
a. Alkylating Agents - Drugs that interfere with cellular metabolism and growth. These drugs are not cell-cycle specific.
b. Antimetabolites - Drugs that block DNA synthesis. They are cell cycle specific.
c. Antibiotics - Inhibit DNA synthesis. Strand splitting occurs with their use.
d. Steroids and Hormones.
2. Some principles that guide the use of chemotherapy medications
a. Chemotherapy drugs, when given in a combination that is carefully designed, are more therapeutic than when given singly.
b. The goal of chemotherapy is total remission.
c. The first attempt gives the best chance for a significant response, so the type of medications used as well as the dose should be the approach that would give the best result.
d. The highest possible doses should be used to get maximum tumor-cell kill.
e. There are various ways of giving the medications to reduce toxicity. For example, increasing the length of time of administration of the drug may decrease side effects without altering the needed dose.
3. Adverse effects of Chemotherapy
a. GI tract - nausea, vomiting, diarrhea, stomatitis, loss of appetite
b. Skin - loss of hair, itching, dermatitis, changes in skin color
c. Blood - anemia, leukopenia, thrombocytopenic,
d. Reproductive - cessation of menstruation, infertility, decreased sexual drive
e. Urinary - nephrotoxicity, hematuria, pain on urination
f. Neurologic - ototoxicity, peripheral neuropathies
g. Musculoskeletal - myalgia
h. Respiratory - pneumonitis, pulmonary fibrosis
B. Radiation
1. DNA is the target of radiation therapy. Cellular death occurs because radiation causes single and double stranded breaks in chromosomes rendering the cells incapable of proliferation
2. Different Radiation delivery systems
a. External beam radiation which is the most common
b. Implant therapy
c. Isotope therapy where the radiation source is sealed.
d. Combination of heat and radiation
3. Side effects of radiation therapy
a. Dependent upon the site of the therapy, the amount of tissue irradiated, the dosage delivered, and the amount of time of each radiation treatment.
b. External beam radiation can cause burns to the skin with wet or dry desquamation.
C. Surgery
D. Immunological therapies for cancer
1. Vaccines - There is a clinical trial for a vaccine for melanoma. This trial is in its final stages. Doctors think that vaccines will be used in conjunction with traditional therapies to kill the cancer cells that are left.
2. Cytokines (Interferon, IL -2 and TNF) that stimulate production of immune cells
3. Monoclonal antibodies - There is research where they are using B cells to make specific antibodies for a specific type of cancer. They are also combining the monoclonal antibodies with drugs, toxins, or radioactive materials. These antibodies can then carry the chemicals to destroy specific cancer cells.
4. Gene therapy - research is being done where a gene is injected into the tumor cells. This causes the cells to show a foreign ID marker. Hopefully, the use of gene therapy will cause the body to see the tumor cells as non-self and destroy the tumor cells
E. Antiangiogenesis - the target is the tumor's vasculature. The tumor, as was discussed earlier, destroys surrounding tissue and creates its own blood supply. This therapy is directed at destroying the blood supply to the tumor, thus cutting off its source of nutrients.

Front 13

5. Identify the adverse effects of certain cancer therapies.
P 396

Back 13

Read, too much to list.

Front 14

6. Describe how monoclonal antibodies assist in the diagnosis and treatment of cancer.
P 396

Back 14

Read, too much to list.