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ONCOLOGY
Epidemiology
Leading causes of death
Percentage of Total Deaths, US
Heart Diseases Cancer Cerebrovascular Diseases Chronic Obstructive Lung Diseases Accidents Pneumonia & Influenza Diabetes Mellitus Suicide Homicide HIV Infection
31.4 23.3 6.9 4.7 4.1 3.7 2.7 1.3 0.9 0.7
Cancer Biology
NORMAL CELLS
Blood vessel
Few mitoses
Loss of contact inhibition Increase in growth factor secretion Increase in oncogene expression Loss of tumor suppressor genes Neovascularization
Primary Neoplasm
Metastases
TRANSFORMATION
METASTASIS
Tumorigenesis
Normal cell
Kastan MB. Cancer: Principles & Practice of Oncology. 5th ed. 1997;121-134.
Exponential growth
Normal cell
1 million cells (20 doublings) undetectable
Dividing
16 cells
109
time
Undetectable cancer Detectable cancer
Host death
Chemotherapuetic Agents
Effects of chemotherapy
Selective toxicity based on characteristics that distinguish malignant cells from normal cells Antineoplastic effects Cell death Cell growth inhibited Cell differentiation
Haskell CM. Cancer Treatment. 4th ed. 1995;32.
Mostly antiproliferative Action during the S phase of the cell cycle No specific inhibitory effect on invasiveness, loss of differentiation
Cytotoxic drugs act on dividing cells (both cancer and normal cells) They will affect all rapidly dividing normal tissues
Cytotoxic agents
Alkylating agents: Mechanism of action Polyfunctional compounds which alkylate efficiently either directly or after being metabolized Cytotoxicity results from alkylation of guanine and interference with DNA replication/transcription to RNA Cell-cyclephase nonspecific (although dividing cells are more prone to their action)
Gerson SL. Current Cancer Therapeutics. 3rd ed. 1998;1.