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      Hypoxia Imaging Endoscopy Equipped with Laser Light Source from Preclinical Live Animal Study to First-In-Human Subject Research

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          Abstract

          A goal in next-generation endoscopy is to develop functional imaging techniques to open up new opportunities for cancer diagnosis. Although spatial and temporal information on hypoxia is crucial for understanding cancer physiology and expected to be useful for cancer diagnosis, existing techniques using fluorescent indicators have limitations due to low spatial resolution and invasive administration. To overcome these problems, we developed an imaging technology based on hemoglobin oxygen saturation in both the tumor and surrounding mucosa using a laser endoscope system, and conducted the first human subject research for patients with aero-digestive tract cancer. The oxygen saturation map overlapped the images of cancerous lesions and indicated highly heterogeneous features of oxygen supply in the tumor. The hypoxic region of the tumor surface was found in both early cancer and cancer precursors. This technology illustrates a novel aspect of cancer biology as a potential biomarker and can be widely utilized in cancer diagnosis.

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          Most cited references12

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          Hypoxia-inducible factors, stem cells, and cancer.

          Regions of severe oxygen deprivation (hypoxia) arise in tumors due to rapid cell division and aberrant blood vessel formation. The hypoxia-inducible factors (HIFs) mediate transcriptional responses to localized hypoxia in normal tissues and in cancers and can promote tumor progression by altering cellular metabolism and stimulating angiogenesis. Recently, HIFs have been shown to activate specific signaling pathways such as Notch and the expression of transcription factors such as Oct4 that control stem cell self renewal and multipotency. As many cancers are thought to develop from a small number of transformed, self-renewing, and multipotent "cancer stem cells," these results suggest new roles for HIFs in tumor progression.
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            Association between tumor hypoxia and malignant progression in advanced cancer of the uterine cervix.

            Experimental tumors contain a significant fraction of microregions that are chronically or transiently hypoxic. Experimental evidence showing that hypoxia (and subsequent reoxygenation) may have a profound impact on malignant progression and on responsiveness to therapy is growing. The clinical relevance of tumor oxygenation in human solid malignancies is under investigation. We have developed and validated a clinically applicable method for measurement of tumor oxygenation in locally advanced cancer of the uterine cervix using a computerized polarographic electrode system. Applying this procedure in patients with cervical cancers
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              Evaluation and stages of surgical innovations.

              Surgical innovation is an important part of surgical practice. Its assessment is complex because of idiosyncrasies related to surgical practice, but necessary so that introduction and adoption of surgical innovations can derive from evidence-based principles rather than trial and error. A regulatory framework is also desirable to protect patients against the potential harms of any novel procedure. In this first of three Series papers on surgical innovation and evaluation, we propose a five-stage paradigm to describe the development of innovative surgical procedures.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2014
                10 June 2014
                : 9
                : 6
                : e99055
                Affiliations
                [1 ]Department of Gastroenterology, Endoscopy Division, National Cancer Center Hospital East, Kashiwa, Chiba, Japan
                [2 ]Division of Science and Technology for Endoscopy and Surgery, National Cancer Center Hospital East, Kashiwa, Chiba, Japan
                [3 ]Imaging Technology Center, FUJIFILM Corporation, Kaisei, Kanagawa, Japan
                [4 ]Clinical Trial Section, National Cancer Center, Kashiwa, Chiba, Japan
                [5 ]Department of Pathology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan
                [6 ]Research Institute for Biomedical Sciences, Tokyo University of Science, Noda, Chiba, Japan
                National Cancer Institute, National Institutes of Health, United States of America
                Author notes

                Competing Interests: H. Yamaguchi and T. Saito are employees of FUJIFILM Corporation. This technology has been developed to apply to an endoscope system. K. Kaneko has received grant support and a prototype endoscope system with hypoxia imaging function from Fujifilm Corporation, Tokyo, Japan. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials.

                Conceived and designed the experiments: KK HY AS HE AO. Performed the experiments: KK HY TS TY YO HI MK. Analyzed the data: HY TS SN. Contributed reagents/materials/analysis tools: TS SN. Contributed to the writing of the manuscript: KK HY.

                Article
                PONE-D-14-12131
                10.1371/journal.pone.0099055
                4051687
                24915532
                8a17be88-1273-4408-999b-9b022d420d29
                Copyright @ 2014

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 24 March 2014
                : 17 April 2014
                Page count
                Pages: 9
                Funding
                This work was supported in part by the National Cancer Center Research and Development Fund (23-A-45) and (23-A-15) and the 3rd-term comprehensive 10-Year strategy for Cancer Control by the Ministry of Health, Labour and Welfare, and Accelerating Regulatory Science Initiative (H-24) [ http://www.ncc.go.jp/en/index.html]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine and Health Sciences
                Gastroenterology and Hepatology
                Gastrointestinal Cancers
                Research and Analysis Methods
                Imaging Techniques
                In Vivo Imaging
                Custom metadata
                The authors confirm that all data underlying the findings are fully available without restriction. All data are included within the manuscript.

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