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      Discriminating Hepatocellular Carcinoma in Rats Using a High-T c SQUID Detected Nuclear Resonance Spectrometer in a Magnetic Shielding Box

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          Abstract

          In this study, we report the spin-lattice relaxation rate of hepatocellular carcinoma (HCC) and normal liver tissue in rats using a high-T c superconducting quantum interference device (SQUID) based nuclear magnetic resonance (NMR) spectrometer. The resonance spectrometer used for discriminating liver tumors in rats via the difference in longitudinal relaxation time in low magnetic fields was set up in a compact and portable magnetic shielding box. The frequency-domain NMR signals of HCC tissues and normal liver tissues were analyzed to study their respective longitudinal relaxation rate T 1 −1. The T 1 −1 of liver tissues for ten normal rats and ten cancerous rats were investigated respectively. The averaged T 1 −1 value of normal liver tissue was (6.41±0.66) s −1, and the averaged T 1 −1 value of cancerous tissue was (3.38±0.15) s −1. The ratio of T 1 −1 for normal liver tissues and cancerous liver tissues of the rats investigated is estimated to be 1.9. Since this significant statistical difference, the T 1 −1 value can be used to distinguish the HCC tissues from normal liver tissues. This method of examining liver and tumor tissues has the advantages of being convenient, easy to operate, and stable.

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          Liquid-state NMR and scalar couplings in microtesla magnetic fields.

          We obtained nuclear magnetic resonance (NMR) spectra of liquids in fields of a few microtesla, using prepolarization in fields of a few millitesla and detection with a dc superconducting quantum interference device (SQUID). Because the sensitivity of the SQUID is frequency independent, we enhanced both signal-to-noise ratio and spectral resolution by detecting the NMR signal in extremely low magnetic fields, where the NMR lines become very narrow even for grossly inhomogeneous measurement fields. In the absence of chemical shifts, proton-phosphorous scalar (J) couplings have been detected, indicating the presence of specific covalent bonds. This observation opens the possibility for "pure J spectroscopy" as a diagnostic tool for the detection of molecules in low magnetic fields.
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            Hepatocellular carcinoma: from gene to public health.

            Liver diseases associated with chronic hepatitis B virus (HBV) infection, including hepatocellular carcinoma, account for more than 1 million deaths annually worldwide. In addition to HBV infection, other risk factors are involved in the etiology of hepatocellular carcinoma and, among these, dietary exposure to the carcinogenic aflatoxins is of particular importance in certain regions of southeast Asia and sub-Saharan Africa. The relative contributions of these two risk factors and the mechanism of the interaction between them in the pathogenesis of hepatocellular carcinoma are still poorly understood. The recently developed individual biochemical and molecular markers of aflatoxin exposure, i.e., aflatoxin-albumin adducts in blood and a specific GC to TA transversion mutation in codon 249 of the p53 gene (249ser p53 mutation) in hepatocellular carcinomas, permit a better quantitative estimation of aflatoxin exposure in different populations of the world. A comprehensive summary of the data from our laboratory and the literature, based on a large number (>1000) of individual cases of hepatocellular carcinoma, is presented here and shows the following: 1) A high level and high prevalence of exposure to aflatoxins occur in West Africa, Mozambique, and some regions of China; 2) a high prevalence of the 249ser p53 mutation is detected in these countries; and 3) hepatocellular carcinomas from countries with low or no exposure to aflatoxins show a very low prevalence of the 249ser p53 mutation and distinctly different p53 mutation spectra, probably indicating different etiologies. Experimental and epidemiologic studies demonstrate an interaction between HBV infection and aflatoxins in hepatocarcinogenesis. The relevance of the biochemical/molecular markers of aflatoxin exposure, HBV vaccination, and the reduction of aflatoxin exposure, in addition to the interaction between HBV infection and other risk factors in liver carcinogenesis, are discussed with regard to the implementation of measures for primary prevention.
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              Tissue water content and nuclear magnetic resonance in normal and tumor tissues.

              Pulsed proton nuclear magnetic resonance was used to differentiate between normal and malignant tissues. When the tissue water content varied from 80 to 93%, the tumors exhibited spin-lattice relaxation times (T1) from 0.9 to 1.8 sec. We report also the results obtained on 9-day-old embryos and on liver, brain, and heart from 2-day-old rats. A good correlation between the spin-lattice (T1) and spin-spin (T2) relaxation times and the tissue water content was found for all tissues studied. The relaxation times T1 and T2 and water content in Walker 256 carcinoma and its lymph node metastasis were quite similar.
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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
                2012
                5 October 2012
                : 7
                : 10
                : e47057
                Affiliations
                [1 ]Department of Surgery and Angiogenesis Center, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
                [2 ]Institute of Electro-optical Science and Technology, National Taiwan Normal University, Taipei, Taiwan
                [3 ]Department of Electro-Optical Engineering, Kun Shan University, Tainan, Taiwan
                [4 ]MagQu Co Ltd. Sindian Strict, New Taipei City, Taiwan
                [5 ]Graduate Institute of Applied Physics and Department of Physics, National Taiwan University, Taipei, Taiwan
                Mount Sinai School of Medicine, United States of America
                Author notes

                Competing Interests: One author, Dr. Shieh Yueh Yang, plays two roles of CEO in MagQu Co. and Adjuct Professor in National Taiwan Normal University. He jointed the reseach project (i.e. the declared funding in the manuscript) as his academic role. This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials.

                Conceived and designed the experiments: HCY HEH. Performed the experiments: KWH HHC. Analyzed the data: SHL. Contributed reagents/materials/analysis tools: SYY JJC LMW. Wrote the paper: HCY SHL.

                Article
                PONE-D-12-10537
                10.1371/journal.pone.0047057
                3465302
                23071710
                5f3fd43f-d64f-415f-9df0-9a2848d0f618
                Copyright @ 2012

                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
                : 6 April 2012
                : 7 September 2012
                Page count
                Pages: 7
                Funding
                This work was supported by the National Science Council of Taiwan under grant number NSC99-2112-M002-017-MY3, NSC 100-2120-M-002-015, NSC101-2120-M168-001, and the Department of Health under grant number DOH100-TD-N-111-008, DOH101-TD-N-111-004. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology
                Biophysics
                Radiation Biophysics
                Biotechnology
                Bioengineering
                Histology
                Radiobiology
                Engineering
                Bioengineering
                Biological Systems Engineering
                Biomedical Engineering
                Medical Devices
                Systems Engineering
                Materials Science
                Material Properties
                Magnetic Properties
                Materials Characterization
                Materials Physics
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                Medicine
                Clinical Research Design
                Diagnostic Medicine
                Clinical Laboratory Sciences
                Gastroenterology and Hepatology
                Liver Diseases
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                Radiation Biophysics
                Interdisciplinary Physics
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                Nuclear Physics
                Radiometry

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