Pathophysiology - Biology of Cancer
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What is neoplasia?
A new abnormal growth that could be either benign or malignant. Includes a loss of responsiveness to normal growth controls.
What is a tumor?
A new abnormal growth could be either benign or malignant.
What does benign mean?
"Relatively innocent," remains localized and doesn't spread.
What does malignant mean?
Cancer, can invade and destroy adjacent structures and spread to distant sites.
What suffix is designated for benign tumors?
- Adenoma - glandular tumor
- Cystadenoma - mass on hollow organ
What are 2 malignant exceptions to the "-oma" rule?
What are the 3 main categories of malignant tumors?
-sarcoma: connective tissue (fibrosarcoma, osteosarcoma)
-carcinoma: epithelial (adencarcinoma)
- Lymphoma and leukemia: Solid mass of tissue and bloodstream/bone marrow proliferation
What are some risk factors for cancer?
Genetics, viruses, bacteria, tobacco use, diet (low fiber, obesity), alcohol consumption, sexual/reproductive behavior, air pollution, occupational hazards, UV radiation, ionizing radiation, sex hormones.
What does damage to "social-control genes" result in?
Carcinogenesis: molecular basis for cancer.
What is an oncogene?
A regulatory gene that, if damaged, can lead to neoplasia.
What is a proto-oncogene?
Genes that in their normal, non-mutant state, that lead to proliferation of cells (progrowth).
What are tumor-suppressor genes?
Genes that in their normal, nonmutant state, stop excessive cell proliferation (antigrowth).
What are "proof-reading" genes?
Genes that code for DNA error; repair enzymes.
What is differentiation?
When normal cells become irreversibly more specialized. More focus and less diversity. More differentiation = less replictation.
What is telomer?
The normal cap of DNA at the end of a chromosome.
What is telomerase?
An enzyme that can build up the telomer and keep a chromosome "alive".
What 3 factors define neoplasia?
- Autonomy: cells gain independence from normal regulation
- Anaplasia: total loss of differentiation
- Transformation: process by which normal cell becomes a tumor cell.
What mutations are required for the transformation into cancer?
Self-sufficiency in growth signals, insensitivity to anti-growth signals, limitless replicative potential, sustained angiogenesis, tissue invasion and metastasis.
How does differentiation in tumor cells refer to?
The extent to which tumor cells resemble their normal forebears.
How are benign tumor cells differentiated?
Well-differentiated and may even produce funtional hormones.
How are malignant tumor cells differentiated?
Range from well-differentiated to anaplastic.
What is dysplasia?
A disorderly but non-neoplastic proliferation of (usually epithelial) cells. May be reversible. Often found adjacent to cancerous foci.
What are 3 characteristics of dysplasia?
- Pleomophism: loss of uniformity
- Loss of architectual orientation
- Mitotic figures more abundant and in abnormal locations
What is carcinoma in situ?
Pre-invasive epithelial tumors (not pre-cancerous) which have not yet broken the basement membrane.
Benign and malignant tumors differ on what basis?
Differentiation, anaplasia, rate of growth, local invasion (malignant), metastasis (malignant)
What is anaplasia?
Cells which show the most extreme disturbances in cell growth. Mitoses are numerous and abnormal.
What is pleomorphism?
Cells that show marked variation in size/shape.
What is characteristic of the nuclei in anaplastic cells?
Hyperchromic, large, and pleomorphic.
How do benign and malignant tumors differ in rate of growth?
Benign tumors are slow while malignant show a wide variation in their rate of growth.
When do benign tumors grow faster/ slower than usual?
- Influenced by circulating hormone
- Pressure constraints
What do rapidly growing cancers often develop?
Central areas of ischemic necrosis due to loss of blood supply.
When do cancers develop necrotic centers?
When they outgrow their vascular supply by 1-2 mm.
Angiogenesis inhibitors have potential for use as treatment.
What does "doubling time" refer to in regards to tumor cell growth?
Cells may be triggered to cycle more readily, but do not complete the cycle faster.
What is the growth fraction?
The proportion of cells within the tumor that are replicating.
What is the clinical importance of tumor growth kinetics?
Chemotherapy is only effective on cancer cells actively in the growth cycle.
Surgically fucking the tumor with some raditation can cause cells to enter active growth making them more susceptible to chemotherapy.
How do benign tumors demonstrate local growth?
They remain localized at site of origin and slowly expand. Develop an enclosing fibrous capsule.
How do cancers demonstrate local invasion?
Cancers grow by progressive infiltration, invasion, destruction, and penetration of the surrounding tissue.
Malignant tumor cells have high levels of lytic enzymes
Decreased cell-to-cell adhesion and increased cell motility
What is special about the biology of tumor cells?
Tumor cells are better adapted to survive under unfavorable conditions.
Require less oxygen, fewer mitchondria, and are better fitted to tolerate lactic acid by-products.
What are the growth properties of tumor cells in a cell culture?
Normal cells echibit contact inhibition with a finite lifespan.
Cancer cells can float in suspended clumps; anchorage independent.
What is metastasis?
Spread of cancer cells from a primary site of origin to a distant site.
Large, anaplastic neoplasms are (more/less) likely to metastasize?
What are 3 steps involved with metastasis?
1) Invasion and penetration into blood vessels and enter circulation
2) Transport to a second site
3) Arrest, adherence, and proliferation at the secondary site. (stop, stick, start growing)
What are the 3 ways malignant neoplasms disseminate?
- Lymphatic spread
- Hematogenous spread
What is an example of "skip metastasis"?
Metastasis by lymphatic spread that skips lymph nodes in a path of cancer-ishness.
What are some characteristics of metastasis by hematogenous spread?
Arteries are less readily penetrated than are veins. Liver and lungs are frequently involved secondary sites.
What are 3 possible effects of tumors on the host?
- Fake hormone production
- Ulceration causing possible secondary infection
What are 4 common clinical manifestations of cancer?
- Cancer cachexia
- Paraneoplastic syndromes
What is cancer cachexia?
A wasting syndrome; progrressive loss of body fat and lean body mass; increased basal metabolic rate.
What are 3 examples of paraneoplastic syndromes?
- Cushing's syndrome
What system is used to grade and stage cancer?
T - Tumor N - Nodes M - Metastases
T: 0 - tumor free 1 - <2cm 2 - 2-5cm 3 - beyond organ
N: 0 - no nodes 1 - adjacent nodes 2 - distant nodes
M: 0 - none 1 - demonstrable
What cancer has the highest incidence in males and in females?
Prostate and breast cancer
What cancer has the highest mortality rate?
Lung cancer in (males and females)
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