Biomedical Engineering Reference
In-Depth Information
4 Cancer as a Microcosm of Embryogenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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4.1 Soil and Seed . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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4.2 Metastasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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4.3 Elimination, Equilibrium, and Escape . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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5 Central Importance of the Stroma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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6 Breast Cancer Stem Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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7 Multistep Carcinogenesis and DNA Repair . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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8 The Origins of the Tumor-Initiating Cell . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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9 Activation of Stem Cells and Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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10 Tumor Suppressor Genes and Cancer-Initiating Cells . . . . . . . . . . . . . . . . . . . . .
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11 Stem Cell Activation and Specific Cancers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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12 SP Cells in Tumors and Cell Lines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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13 Major Cancers and Risk Factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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13.1 Cancer Therapy ''Causes'' Cancers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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14 How the Stem Cell Paradigm Suggests New Approaches . . . . . . . . . . . . . . . . . . .
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15 Future Research . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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16 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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1 Introduction
The fertilized oocyte is a totipotent stem cell, capable of giving rise to all the cell
types of the embryo and the trophoblast (Gilbert et al., 2006; Kimball, 2003).
Even after the first few divisions, embryonic cells give rise to totipotent stem cells,
those capable of recreating an entire organism (Seydoux and Braun, 2006).
Twinning is often a result of early embryo splitting and subsequent totipotent
development (Hall, 2003; Stevenson and Hall, 2006). Embryonic germ cells and
embryonic carcinoma cells are each types of pluripotent stem cells that can be
isolated from embryonic or fetal tissue or germ cell tumors. These pluripotent
stem cells can be grown in culture to some extent, using feeder layers and growth
factors to maintain differentiation capacity. Pluripotent stem cells have a
restricted differentiation capacity as compared with totipotent stem cells. There
are a plethora of recent reports of both totipotent and pluripotent mammalian
stem cells growing in culture: Some of these have been used for mammalian
cloning experiments (Jaenisch et al., 2004). Each tissue, as it differentiates, gives
rise to the multipotent stem cells of the body (Tsonis, 2007). For example, the
hematopoietic stem cell is capable of giving rise to all of the cells in the blood
(Lagasse et al., 2000; Till et al., 1964). All stem cells have the property of giving
rise to additional stem cells when they divide. This property is self-renewal
(Rajaraman et al., 2006). As self-renewal occurs, cells confront a decision point.
At this point, cells commit to differentiate and eventually stop dividing, under-
going senescence or apoptosis, or continue dividing (Alberts, 2008; Till et al.,
1964). When the decision point results in self-renewal, it permits a nearly immor-
tal lifespan for the stem cell (Schlessinger and Van Zant, 2001). The mechanism
underlying the self-renewal decision point is a subject of active investigation
(McKenzie et al., 2006; Morrison et al., 1997). Some stem cells, such as
