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Mitogens stimulate G1-Cdk and G1/S-Cdk activities
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p27 suppresses CdK activity
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The Rb protein acts as a brake in mammalian cells
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Excessive stimulation of mitogenic pathways leads to cell cycle arrest or apoptosis
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Cell growth like cell division is also stimulated by extracellular signals
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Comparison of nerve cell size vs. lymphocyte size
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Cancer
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Cancer incidence and mortality in the United States
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Tumors can not be detected until 10 8 to 10 9 cells are present
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Why doesn’t cancer happen more often? 10 16 cell divisions in a human lifetime. 10 -6 mutations per gene per cell division a single gene will undergo mutations in 10 10 occasions during a humans lifetime
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Cancer is caused by a slow accumulation of numerous random mutations in a single cell line
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Cancers develop in slow stages from mildly aberrant cells
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Cancer incidence as a function of age
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Delayed onset of cancer following exposure to 2-naphthylamine
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Age adjusted cancer death rates in the U.S. femalesmales
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The Ames Test for Mutagenicity
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Metastasis from carcinoma of the prostrate gland
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Benign vs. Malignant Tumors
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Melanoma cells with low filamin levels crawl poorly and tend not to metastasize
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When filamin levels are restored the cells move normally and become highly metastatic
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Filamin crosslinks actin into 3-dimensional networks with gel-like properties
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Cancer results from somatic mutations The Philadelphia chromosome is associated with one type of leukemia
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Chromosomes from breast tumors may display abnormalities in structure and number
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Rb protein control of the cell cycle
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The Rb protein acts as a brake in mammalian cells
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Six ways of losing the remaining good copy of a tumor suppressor gene
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When proto-oncogene becomes overactive it becomes an oncogene
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Myc Gene Amplification
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Mitogens stimulate G1-Cdk and G1/S-Cdk activities
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Ocogene collaboration in transgenic mice
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Viruses May cause Cancer Papillomavirus causes warts and subverts the control of cell division
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Pap smears normalabnormalinvasive
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How papillomaviruses are thought to give rise to cancer of the uterine cervix
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Activation of cell proliferation by DNA tumor virus
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Sequence of genetic changes underlying the development of a colorectal carcinoma
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Each tumor will contain a different set of mutations
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Effect of ionizing radiation on normal and cancer cells
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