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Role of p53 in Anticancer Drug Treatment- and Radiation-Induced Injury in Normal Small Intestine.

Jin S - Cancer Biol Med (2012)

Bottom Line: In the human gastrointestinal tract, the functional mucosa of the small intestine has the highest capacity for absorption of nutrients and rapid proliferation rates, making it vulnerable to chemoradiotherapy.A traditional p53 inhibitor and two other molecules that exhibit strong protective effects on normal small intestinal epithelium during anticancer drug treatment and radiation therapy are introduced in this work.The objective of this review was to update current knowledge regarding potential mechanisms and targets that inhibit the side effects induced by chemoradiotherapy.

View Article: PubMed Central - PubMed

Affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, School of Medicine, The Johns Hopkins University, Baltimore, MD 21210, USA.

ABSTRACT
In the human gastrointestinal tract, the functional mucosa of the small intestine has the highest capacity for absorption of nutrients and rapid proliferation rates, making it vulnerable to chemoradiotherapy. Recent understanding of the protective role of p53-mediated cell cycle arrest in the small intestinal mucosa has led researchers to explore new avenues to mitigate mucosal injury during cancer treatment. A traditional p53 inhibitor and two other molecules that exhibit strong protective effects on normal small intestinal epithelium during anticancer drug treatment and radiation therapy are introduced in this work. The objective of this review was to update current knowledge regarding potential mechanisms and targets that inhibit the side effects induced by chemoradiotherapy.

No MeSH data available.


Related in: MedlinePlus

Model for the cell lineage in small intestinal crypts. The small intestinal epithelium consists of two main structures: villi (luminal protrusions) and crypts (invaginations). The villi are composed of fully differentiated cells that mediate absorption and secretion. Apoptosis of the cells at the tip of villi and the proliferation of crypt cells maintain the number of functional cells in the small intestinal epithelium. All cell types within an individual crypt are sustained by stem cells located at the bottom of the crypt. Two stem cell positions have been reported for crypts: One represents +4 position stem cells [20] (shown between the dotted curve lines), and the other refers to CBC cells located between differentiated Paneth cells [21]. Once TA cells divided from the stem cells reach the crypt–villus junction, they differentiate and migrate to the villi.
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f1: Model for the cell lineage in small intestinal crypts. The small intestinal epithelium consists of two main structures: villi (luminal protrusions) and crypts (invaginations). The villi are composed of fully differentiated cells that mediate absorption and secretion. Apoptosis of the cells at the tip of villi and the proliferation of crypt cells maintain the number of functional cells in the small intestinal epithelium. All cell types within an individual crypt are sustained by stem cells located at the bottom of the crypt. Two stem cell positions have been reported for crypts: One represents +4 position stem cells [20] (shown between the dotted curve lines), and the other refers to CBC cells located between differentiated Paneth cells [21]. Once TA cells divided from the stem cells reach the crypt–villus junction, they differentiate and migrate to the villi.

Mentions: The above-mentioned types of differentiated villus cells are derived from common stem cells within intestinal crypts. Historically, stem cells are hypothesized to be located at approximately cell position 4, named “+4 position stem cells”, from the crypt bottom of the small intestine. The first three positions are occupied by terminally differentiated Paneth cells (Figure 1) [20]. Recent research using a genetic approach has shown that cycling crypt base columnar (CBC) cells are actually located in the “stem cell zone” and interspersed between Paneth cells. CBC cells are positive for Lgr5 (leucine-rich repeat-containing G-protein-coupled receptor 5) expression [21].


Role of p53 in Anticancer Drug Treatment- and Radiation-Induced Injury in Normal Small Intestine.

Jin S - Cancer Biol Med (2012)

Model for the cell lineage in small intestinal crypts. The small intestinal epithelium consists of two main structures: villi (luminal protrusions) and crypts (invaginations). The villi are composed of fully differentiated cells that mediate absorption and secretion. Apoptosis of the cells at the tip of villi and the proliferation of crypt cells maintain the number of functional cells in the small intestinal epithelium. All cell types within an individual crypt are sustained by stem cells located at the bottom of the crypt. Two stem cell positions have been reported for crypts: One represents +4 position stem cells [20] (shown between the dotted curve lines), and the other refers to CBC cells located between differentiated Paneth cells [21]. Once TA cells divided from the stem cells reach the crypt–villus junction, they differentiate and migrate to the villi.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3643648&req=5

f1: Model for the cell lineage in small intestinal crypts. The small intestinal epithelium consists of two main structures: villi (luminal protrusions) and crypts (invaginations). The villi are composed of fully differentiated cells that mediate absorption and secretion. Apoptosis of the cells at the tip of villi and the proliferation of crypt cells maintain the number of functional cells in the small intestinal epithelium. All cell types within an individual crypt are sustained by stem cells located at the bottom of the crypt. Two stem cell positions have been reported for crypts: One represents +4 position stem cells [20] (shown between the dotted curve lines), and the other refers to CBC cells located between differentiated Paneth cells [21]. Once TA cells divided from the stem cells reach the crypt–villus junction, they differentiate and migrate to the villi.
Mentions: The above-mentioned types of differentiated villus cells are derived from common stem cells within intestinal crypts. Historically, stem cells are hypothesized to be located at approximately cell position 4, named “+4 position stem cells”, from the crypt bottom of the small intestine. The first three positions are occupied by terminally differentiated Paneth cells (Figure 1) [20]. Recent research using a genetic approach has shown that cycling crypt base columnar (CBC) cells are actually located in the “stem cell zone” and interspersed between Paneth cells. CBC cells are positive for Lgr5 (leucine-rich repeat-containing G-protein-coupled receptor 5) expression [21].

Bottom Line: In the human gastrointestinal tract, the functional mucosa of the small intestine has the highest capacity for absorption of nutrients and rapid proliferation rates, making it vulnerable to chemoradiotherapy.A traditional p53 inhibitor and two other molecules that exhibit strong protective effects on normal small intestinal epithelium during anticancer drug treatment and radiation therapy are introduced in this work.The objective of this review was to update current knowledge regarding potential mechanisms and targets that inhibit the side effects induced by chemoradiotherapy.

View Article: PubMed Central - PubMed

Affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, School of Medicine, The Johns Hopkins University, Baltimore, MD 21210, USA.

ABSTRACT
In the human gastrointestinal tract, the functional mucosa of the small intestine has the highest capacity for absorption of nutrients and rapid proliferation rates, making it vulnerable to chemoradiotherapy. Recent understanding of the protective role of p53-mediated cell cycle arrest in the small intestinal mucosa has led researchers to explore new avenues to mitigate mucosal injury during cancer treatment. A traditional p53 inhibitor and two other molecules that exhibit strong protective effects on normal small intestinal epithelium during anticancer drug treatment and radiation therapy are introduced in this work. The objective of this review was to update current knowledge regarding potential mechanisms and targets that inhibit the side effects induced by chemoradiotherapy.

No MeSH data available.


Related in: MedlinePlus