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      Spatiotemporal switching signals for cancer stem cell activation in pediatric origins of adulthood cancer: Towards a watch-and-wait lifetime strategy for cancer treatment

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          Abstract

          Pediatric origin of cancer stem cell hypothesis holds great promise and potential in adult cancer treatment, however; the road to innovation is full of obstacles as there are plenty of questions left unanswered. First, the key question is to characterize the nature of such stem cells (concept). Second, the quantitative imaging of pediatric stem cells should be implemented (technology). Conceptually, pediatric stem cell origins of adult cancer are based on the notion that plasticity in early life developmental programming evolves local environments to cancer. Technologically, such imaging in children is lacking as all imaging is designed for adult patients. We postulate that the need for quantitative imaging to measure space-time changes of plasticity in early life developmental programming in children may trigger research and development of the imaging technology. Such quantitative imaging of pediatric origin of adulthood cancer will help develop a spatiotemporal monitoring system to determine cancer initiation and progression. Clinical validation of such speculative hypothesis-that cancer originates in a pediatric environment-will help implement a wait-and-watch strategy for cancer treatment.

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          Most cited references52

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          Cancer etiology. Variation in cancer risk among tissues can be explained by the number of stem cell divisions.

          Some tissue types give rise to human cancers millions of times more often than other tissue types. Although this has been recognized for more than a century, it has never been explained. Here, we show that the lifetime risk of cancers of many different types is strongly correlated (0.81) with the total number of divisions of the normal self-renewing cells maintaining that tissue's homeostasis. These results suggest that only a third of the variation in cancer risk among tissues is attributable to environmental factors or inherited predispositions. The majority is due to "bad luck," that is, random mutations arising during DNA replication in normal, noncancerous stem cells. This is important not only for understanding the disease but also for designing strategies to limit the mortality it causes. Copyright © 2015, American Association for the Advancement of Science.
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            The fetal and infant origins of adult disease.

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              Substantial contribution of extrinsic risk factors to cancer development

              Summary Recent research has highlighted a strong correlation between tissue-specific cancer risk and the lifetime number of tissue-specific stem cell divisions. Whether such correlation implies a high unavoidable intrinsic cancer risk has become a key public health debate with dissemination of the ‘bad luck’ hypothesis. Here we provide evidence that intrinsic risk factors contribute only modestly (<10~30%) to cancer development. First, we demonstrate that the correlation between stem-cell division and cancer risk does not distinguish between the effects of intrinsic and extrinsic factors. Next, we show that intrinsic risk is better estimated by the lower bound risk controlling for total stem cell divisions. Finally, we show that the rates of endogenous mutation accumulation by intrinsic processes are not sufficient to account for the observed cancer risks. Collectively, we conclude that cancer risk is heavily influenced by extrinsic factors. These results carry immense consequences for strategizing cancer prevention, research, and public health.
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                Author and article information

                Contributors
                Journal
                World J Stem Cells
                WJSC
                World Journal of Stem Cells
                Baishideng Publishing Group Inc
                1948-0210
                26 February 2018
                26 February 2018
                : 10
                : 2
                : 15-22
                Affiliations
                Neuro-oncology and Stem Cell Research Laboratory, Children’s Hospital of Orange County, Department of Neurology, University of California-Irvine School of Medicine, Orange, CA 92868-3874, United States
                Children's Hospital of Orange County, Department of Surgery, University of California-Irvine School of Medicine, Orange, CA 92868-3874, United States
                Author notes

                Author contributions: Li SC conceived the project and wrote the primary manuscript; Li SC and Kabeer MH revised the manuscript.

                Correspondence to: Shengwen Calvin Li, PhD, Principal Investigator (Scientist), Neuro-oncology and Stem Cell Research Laboratory, Children’s Hospital of Orange County, Department of Neurology, University of California-Irvine School of Medicine, 455 South Main Street, Orange, CA 92868-3874, United States. shengwel@ 123456uci.edu

                Telephone: +1-714-5094964 Fax: +1-714-5094318

                Article
                jWJSC.v10.i2.pg15
                10.4252/wjsc.v10.i2.15
                5840533
                29531638
                a372709a-945a-4c71-9ca7-0d246df927f0
                ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.

                This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial.

                History
                : 22 December 2017
                : 25 January 2018
                : 24 February 2018
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                pediatric origins of adult cancer,imaging of single cells

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