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| 1 | MITOCHONDRIAL REDOX IMAGING FOR CANCER DIAGNOSTIC AND THERAPEUTIC STUDIES显示文摘Mitochondrial redox states provide important information about energy-linked biological processes and signaling events in tissues for various disease phenotypes including cancer.The redox scanning method developed at the Chance laboratory about 30 years ago has allowed 3D highresolution(∼50×50×10µm^(3))imaging of mitochondrial redox state in tissue on the basis of the fluorescence of NADH(reduced nicotinamide adenine dinucleotide)and Fp(oxidized flavoproteins including flavin adenine dinucleotide,i.e.,FAD).In this review,we illustrate its basic principles,recent technical developments,and biomedical applications to cancer diagnostic and therapeutic studies in small animal models.Recently developed calibration procedures for the redox imaging using reference standards allow quantification of nominal NADH and Fp concentrations,and the concentration-based redox ratios,e.g.,Fp/(Fp+NADH)and NADH/(Fp+NADH)in tissues.This calibration facilitates the comparison of redox imaging results acquired for different metabolic states at different times and/or with different instrumental settings.A redox imager using a CCD detector has been developed to acquire 3D images faster and with a higher in-plane resolution down to 10µm.Ex vivo imaging and in vivo imaging of tissue mitochondrial redox status have been demonstrated with the CCD imager.Applications of tissue redox imaging in small animal cancer models include metabolic imaging of glioma and myc-induced mouse mammary tumors,predicting the metastatic potentials of human melanoma and breast cancer mouse xenografts,differentiating precancerous and normal tissues,and monitoring the tumor treatment response to photodynamic therapy.Possible future directions for the development of redox imaging are also discussed. | LIN Z.LI HE N.XU MAHSA RANJI SHOKO NIOKA BRITTON CHANCE | 2009 | Journal of Innovative Optical Health Sciences2009，2，4： | 3 |
| 2 | QUANTITATIVE REDOX SCANNING OF TISSUE SAMPLES USING A CALIBRATION PROCEDURE显示文摘The fluorescence properties of reduced nicotinamide adenine dinucleotide(NADH)and oxidizedflavoproteins(Fp)including flavin adenine dinucleotide(FAD)in the respiratory chain are sensitive indicators of intracellular metabolic states and have been applied to the studies of mitochondrial function with energy-linked processes.The redox scanner,a three-dimensional(3D)low temperature imager previously developed by Chance et al.,measures the in vivo metabolicproperties of tissue samples by acquiring fluorescence images of NADH and Fp.The redox ratios,i.e.Fp/(Fp+NADH)and NADH/(Fp+NADH),provided a sensitive index of the mitochondrialredox state and were determined based on relative signal intensity ratios.Here we report thefurther development of the redox scanning technique by using a calibration method to quantifythe nominal concentration of the fluorophores in tissues.The redox scanner exhibited very goodlinear response in the range of NADH concentration between 165–1318µM and Fp between90–720µM using snap-frozen solution standards.Tissue samples such as human tumor mousexenografts and various mouse organs were redox-scanned together with adjacent NADH and Fpstandards of known concentration at liquid nitrogen temperature.The nominal NADH and Fpconcentrations as well as the redox ratios in the tissue samples were quantified by normalizing the tissue NADH and Fp fluorescence signal to that of the snap-frozen solution standards.This calibration procedure allows comparing redox images obtained at different time,independent of instrument settings.The quantitative multi-slice redox images revealed heterogeneity inmitochondrial redox state in the tissues. | HE N.XU BAOHUA WU SHOKO NIOKA BRITTON CHANCE LIN Z.LI | 2009 | Journal of Innovative Optical Health Sciences2009，2，4： | 2 |
| 3 | This research was supported by E.U.FP6 Integrated Project“Molecular Imaging”LSHG-CT-2003-503259 and E.U.FP7 Collaborative Project“FMT-XCT”.R.F.acknowledges support from the Marie Curie Program EST-MolecImag Early Stage Training MEST-CT-2004-007643.显示文摘We have imaged mitochondrial oxidation-reduction states by taking a ratio of mitochondrial fluorophores:NADH(reduced nicotinamide adenine dinucleotide)to Fp(oxidized flavoprotein).Although NADH has been investigated for tissue metabolic state in cancer and in oxygen deprived tissues,it alone is not an adequate measure of mitochondrial metabolic state since the NADH signal is altered by dependence on the number of mitochondria and by blood absorption.The redox ratio,NADH/(Fp+NADH),gives a more accurate measure of steady-state tissue metabolism since it is less dependent on mitochondrial number and it compensates effectively for hemodynamic changes.This ratio provides important diagnostic information in living tissues.In this study,the emitted fluorescence of mouse colon in situ is passed through an emission filter wheel and imaged on a CCD camera.Redox ratio images of the healthy and hypoxic mouse intestines clearly showed significant differences.Furthermore,the corrected redox ratio indicated an increase from an average value of 0.51±0.10 in the healthy state to 0.92±0.03 in dead tissue due to severe ischemia(N=5).We show that the CCD imaging system is capable of displaying the metabolic differences in normal and ischemic tissues as well as quantifying the redox ratio in vivo as a marker of these changes. | MAHSA RANJI SHOKO NIOKA HE N.XU BAOHUA WU LIN Z.LI DWIGHT L.JAGGARD BRITTON CHANCE | 2009 | Journal of Innovative Optical Health Sciences2009，2，4： | 0 |
| 4 | Citation analysis of the scientific publications of Britton Chance in ISI citation indexes显示文摘Britton Chance was a pioneer in many scientifc fields such as enzymatic reaction kinetis,bioenergetics,metabolism,in vivo NMr,and biophotonics.As an engineer,physical chemist,physicist,physiologist,biophysicist,biochemist,innovator and educator,he had worked indiversifed fields over extended periods bet ween 1926 until his death in 2010,at the age of 97.Inorder to illustrate his scientific career and great impact on research from a new perspective,weemploy scientometric analysis tools to analyze the publications of Britton Chance with datadownloaded from the ISI Citation Indexes in April 2013.We included articles,reviews andproceding papers but excluded meeting abstracts.In total,we obtained 1023 publication recordswith 1236 authors in 266 joumals with 17,114 citations from 1945 to 2013.We show the annualpublications and citations that Britton Chance received from 1945 to 2013,and generate HistCitemaps on the basis of the global citations(GCS)and local(sel)citations(LCS)to show thecitation relationships among the top-30 publications of Britton Chance.Metabolism and the development of physical methods to probe it appear to be the commecting thread of the lifelongresearch of Britton Chance.Furthermore,we generate the joumal map and co-authorship maptoshow the broad scope of research topics and collaborators and the high impacts of the scientificoeuvre of Britton Chance ranging from physics,engineering,chemistry and biology to medicine. | Lin Z.Li Loet Leydesdorff Shoko Nioka Nannan Sun Eugene Garfield | 2014 | Journal of Innovative Optical Health Sciences2014，7，2： | 0 |
| 5 | A NOVEL TIME-SHARED FLUOROMETER GIVES THE MITOCHONDRIAL REDOX STATE AS THE RATIO OF TWO COMPONENTS OF THE RESPIRATORY CHAIN OF THE ANIMAL AND HUMAN BUCCAL CAVITY WITH QUANTITATIVE MEASURES OF THE REDOX ENERGY STATE显示文摘The source of energy for life is the tissue mitochondria and they demand a complex chain of biochemicals to ensure proper physiological function.Classically,the blood levels,and not the tissue levels of these metabolites,are determined by expensive and time-consuming biochemical analyses.Since the tissue mitochondria are the consumers of the substrates of glycolysis and of fatty acid metabolism,their redox state is a unique accessible monitor of tissue metabolism and its blockade due to toxins. | BRITTON CHANCE SHOKO NIOKA AQUO JENQ-RUEY HORNG | 2010 | Journal of Innovative Optical Health Sciences2010，3，4： | 0 |
| 6 | IMAGING REDOX STATE HETEROGENEITY WITHIN INDIVIDUAL EMBRYONIC STEM CELL COLONIES显示文摘Redox state mediates embryonic stem cell(ESC)differentiation and thus offers an important complementary approach to understanding the pluripotency of stem cells.NADH redox ratio(NADH/(Fp t NADH)),where NADH is the reduced form of nicotinamide adenine dinucleotide and Fp is the oxidizedflavoproteins,has been established as a sensitive indicator of mitochondrial redox state.In this paper,we report our redox imaging data on the mitochondrial redox state of mouse ESC(mESC)colonies and the implications thereof.The low-temperature NADH/Fp redox scanner was employed to image mESC colonies grown on a feeder layer of gamma-irradiated mouse embryonicfibroblasts(MEFs)on glass cover slips.The result showed significant heterogeneity in the mitochondrial redox state within individual mESC colonies(size:~200-440μm),exhibiting a core with a more reduced state than the periphery.This more reduced state positively correlates with the expression pattern of Oct4,a well-established marker of pluripotency.Our observation is thefirst to show the heterogeneity in the mitochondrial redox state within a mESC colony,suggesting that mitochondrial redox state should be further investigated as a potential new biomarker for the stemness of embryonic stem cells. | HE N.XU RUSSELL C.ADDIS DAVIDA F.GOINGS SHOKO NIOKA BRITTON CHANCE JOHN D.GEARHART LIN Z.LI | 2011 | Journal of Innovative Optical Health Sciences2011，4，3： | 0 |
| 7 | INTRODUCTION SPECIAL ISSUE IN MEMORY OF PROFESSOR BRITTON CHANCE显示文摘Britton Chance:One of the Most Outstanding Scientists in the World On June 3rd and 4th,2011,over 300 scientists and professionals from all over the world gathered at the Translational Research Center of the University of Pennsylvania to attend a memorial symposium on\Britton Chance:His Life,Times and Legacy'and a\Molecular Spectroscopy/Imaging Workshop:from bench top to bedside'dedicated to Britton Chance as well. | Lin Z.Li Shoko Nioka | 2011 | Journal of Innovative Optical Health Sciences2011，4，3： | 0 |
| 8 | HISTORY AND PRESENT STATE OF TRANSLATIONAL ELECTRO-OPTICAL APPLICATIONS TO MEDICINE显示文摘This paper reviews the history of the optoelectric devices applied to biomedical sciences in 20th century.It describes history of Vacuum tubes and Spectroscopies with the author’s personal experiences,especially doublebeam spectroscopy.Further,the present developments of Near Infra Red(NIR)devices are described in translational biomedical applications.It includes particulary micro optoelectronics developments and present status of NIR breast cancer detection.Lastly,intrinsic molecular biomarkers are discussed especially NIR measurements of angiogenensis,hypermetabolism and heat production for cancer detection. | BRITTON CHANCE SHOKO NIOKA | 2008 | Journal of Innovative Optical Health Sciences2008，1，1： | 0 |
| 9 | ANAGRAM PROBLEM-SOLVING AND LEARNING IN ANTERIOR PREFRONTAL CORTEX显示文摘We utilized Near-Infrared(NIR)spectroscopy to closely investigate the activation change in anterior prefrontal cortex(aPFC)during verbal anagram problem-solving and learning.We used a parametric design of anagram-solving with three difficulty levels and evaluated anagram skill with two sets of subjects and protocols.The first protocol was a one-time evaluation of untrained subjects(n=10)and the second protocol evaluated subjects over 6 weeks of training(n=6).The untrained subjects in the first protocol demonstrated blood oxygenation corresponding to neuronal activation in the aPFC in response to medium and hard difficulty levels of the stimuli,while the easy anagram task deoxygenated the aPFC bilaterally,corresponding to deactivation.Higher performers have more aPFC activation than lower performers in the medium difficulty level anagram-solving task.Six weeks of training in the second protocol showed that training reduced oxygenation in aPFC.In particular,subjects with lower baseline skill in anagram production showed a larger reduction in oxygenation where true performance gains occurred(medium difficulty)and smaller reduction where the performance gains were limited(hard anagrams).Association of the aPFC activation with the difficulty of the complex task suggests that aPFC is a part of a circuit for execution of task performance.In addition,more use of aPFC by untrained high performers suggests that the role of the aPFC is to increase efficiency of a problem-solving task.Thus,the NIR spectroscopy showed that the aPFC is a key structure in the circuit implementing the development of anagram skill. | SHOKO NIOKA JOSEPH I.TRACY SHANE RAINES SCOTT BUNCE BRITTON CHANCE | 2008 | Journal of Innovative Optical Health Sciences2008，1，2： | 0 |
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