finger-stick-blood-sampling-methodology-for-determination-exercise

Finger-stick Blood Sampling Methodology for the Determination of Exercise-induced Lymphocyte Apoptosis

Exercise is a physiological stimulus capable of inducing apoptosis in immune cells. To date, various limitations have been identified with the measurement ...

Identification of the critical pathways involved in tumorigenesis should ultimately lead to the design of better anticancer agents that target specific components of the disrupted pathways. Murine models of spontaneous cancer in which tumor formation is dependent on defined genetic alterations provide a powerful test system for evaluating the therapeutic efficacy of pathway-specific antineoplastics. We have generated a conditional mouse model for retinoblastoma-dependent sporadic cancer that permits noninvasive monitoring of pituitary tumor development in live animals via in vivo bioluminescence imaging of luciferase expression. We show that the high sensitivity of bioluminescence imaging can be used for noninvasive detection of luciferase expression in pituitary glands from tumor-free animals and for in vivo quantitation of tumor burden over a large dynamic range. This mouse model permits longitudinal monitoring of tumor onset, progression, and response to therapy and may be used effectively for testing cancer prevention and treatment strategies based on therapeutics that specifically target the retinoblastoma pathway.

Noninvasive imaging of spontaneous retinoblastoma pathway-dependent tumors in mice.

Nichtinvasive Bildgebung der spontanen Retinoblastom-Weg-abh&#xE4;ngigen Tumoren in M&#xE4;usen.

The ability to noninvasively quantitate tumor burden from conditional (Cre/loxP-dependent) mouse cancer models would greatly increase their range of useful applications. We now report the generation of a reporter mouse that enables visualization of spontaneous tumor development from pre-existing conditional mouse tumor models via in vivo bioluminescence imaging. We demonstrate that bioluminescence can be "switched-on" in a Cre-dependent manner in every organ analyzed, and that this gives rise to between a 4 and 6-log increase in light emission per mg of wet tissue weight. Furthermore, we highlight the utility of this reporter by showing that it can be used as a sensitive means to measure spontaneous Kras2(v12)-induced lung tumorigenesis in a pre-existing mouse model of non-small cell lung cancer. Taken together, our results suggest that this reporter may be combined with a wide-range of other Cre/loxP tumor mouse models, irrespective of their tissue specificity and render them immediately amenable to longitudinal monitoring of tumor growth and therapeutic response with a noninvasive in vivo imaging approach.

The generation of a conditional reporter that enables bioluminescence imaging of Cre/loxP-dependent tumorigenesis in mice.

Die Erzeugung einer bedingten Reporter, Biolumineszenz-Bildgebung von Cre / loxP-abh&#xE4;ngigen Tumorgenese in M&#xE4;usen erm&#xF6;glicht.

Many mosquito control agencies use carbon dioxide-baited traps as surveillance tools for adult vector populations. However, decisions regarding the number and location of trap sites and the frequency of collections are often based on logistical issues, and not on the bionomics or spatial distribution of the target species. Therefore, with the aim of providing practical information for adult mosquito surveillance programs, we used an array of 81 carbon dioxide- and octenol-baited lights traps to obtain weekly samples of adult mosquitoes in Redland Shire in southeastern Queensland, Australia. The spatial patterns of four different mosquito species were examined, and positive spatial autocorrelation in trap counts was evident for Ochlerotatus vigilax (Skuse), Coquillettidia linealis (Skuse), and Culex annulirostris Skuse, but not for the container species Ochlerotatus notoscriptus (Skuse). Of the three species that exhibited spatially correlated trap counts, the autocorrelation was greatest in Oc. vigilax at a lag distance of 0-1.5 km, with Moran's I values of 0.30-0.64. Moran's I indices were also positive and statistically significant (P < 0.05) at lag distances of 1.5-3.0 and 3.0-4.5 km on each of the 15 sampling occasions. However, at 3.0-4.5 km the Moran's I values were low, which indicated only weak spatial autocorrelation in trap counts. Universal kriging was used to estimate the numbers of each species at unsampled locations throughout the study area, and leave-one-out cross validation analyses indicated that this was a robust method for Cq. linealis and Oc. vigilax. In contrast, trap counts for the container-breeding species Oc. notoscriptus were randomly distributed and the interpolated counts were not reliable. Comparisons of weekly contour maps of adult mosquito counts indicated a consistent spatial pattern for Oc. vigilax and Cq. linealis. Particular geographic areas had consistently high or low numbers of vectors, and these patterns were stable from year to year. Definition of geographic areas with consistently high or low numbers of vectors may allow control activities to be focused in areas with the greatest risk of arbovirus transmission.

Spatial statistical analysis of adult mosquito (Diptera: Culicidae) counts: an example using light trap data, in Redland Shire, Southeastern Queensland, Australia.

R&#xE4;umliche statistische Analyse von erwachsenen M&#xFC;cke (Diptera: Culicidae) z&#xE4;hlt: ein Beispiel mit Lichtfalle Daten, in Redland Shire-, S&#xFC;dost-Queensland, Australien.

Significant progress has been made recently in the variety of ways that cancer can be non-invasively imaged in murine tumour models. The development and continued refinement of specialized hardware for an array of small animal imaging methodologies are only partly responsible. So too has been the development of new imaging techniques and materials that enable specific, highly sensitive and quantitative measurement of a wide range of tumour-related parameters. Included amongst these new materials are imaging probes that selectively accumulate in tumours, or that become activated by tumour-specific molecules in vivo. Other tumour imaging strategies have been developed that rely upon the detection of reporter transgene expression in vivo, and these too have made a significant impact on both the versatility and the specificity of tumour imaging in living mice. The biological implications resulting from these latest advances are presented here, with particular emphasis on those associated with MRI, PET, SPECT, BLI, and fluorescence-based imaging modalities. Taken together, these advances in tumour imaging are set to have a profound impact on our basic understanding of in vivo tumour biology and will radically alter the application of mouse tumour models in the laboratory.

Advances in imaging mouse tumour models in vivo.

Fortschritte in bildgebenden Maustumormodellen in vivo.

Several transgenic mouse models of prostate cancer have been developed recently that are able to recapitulate many key biological features of the human condition. It would, therefore, be desirable to employ these models to test the efficacy of new therapeutics before clinical trial; however, the variable onset and non-visible nature of prostate tumor development limit their use for such applications. We now report the generation of a transgenic reporter mouse that should obviate these limitations by enabling noninvasive in vivo bioluminescence imaging of normal and spontaneously transformed prostate tissue in the mouse. We used an 11-kb fragment of the human prostate-specific antigen (PSA) promoter to achieve specific and robust expression of firefly luciferase in the prostate glands of transgenic mice. Ex vivo bioluminescence imaging and in situ hybridization analysis confirmed that luciferase expression was restricted to the epithelium in all four lobes of the prostate. We also show that PSA-Luc mice exhibit decreased but readily detectable levels of in vivo bioluminescence over extended time periods following androgen ablation. These results suggest that this reporter should enable in vivo imaging of both androgen-dependent and androgen-independent prostate tumor models. As proof-of-principle, we show that we could noninvasively image SV40 T antigen-induced prostate tumorigenesis in mice with PSA-Luc. Furthermore, we show that our noninvasive imaging strategy can be successfully used to image tumor response to androgen ablation in transgenic mice and, as a result, that we can rapidly identify individual animals capable of sustaining tumor growth in the absence of androgen.

Noninvasive bioluminescence imaging of normal and spontaneously transformed prostate tissue in mice.

Mehrere transgene Mausmodelle von Prostatakrebs wurden vor kurzem entwickelt, die viele wichtige biologische Funktionen des Menschseins zu rekapitulieren k&ouml;nnen. Es daher w&auml;re w&uuml;nschenswert, diese Modelle zu testen die Wirksamkeit von neuen Therapeutika vor der klinischen Pr&uuml;fung zu besch&auml;ftigen; jedoch begrenzen die Variable einsetzen und unsichtbare Natur der Prostata Tumor-Entwicklung ihrer Verwendung f&uuml;r solche Anwendungen. Wir berichten nun die Generierung einer transgenen Reporter-Maus, die diese Einschr&auml;nkungen durch Aktivieren von in-vivo Biolumineszenz nichtinvasive Bildgebung der Normal umgehen sollte und spontan verwandelt Prostatagewebe in der Maus. Wir verwendeten ein 11-kb-Fragment des Projekttr&auml;gers menschlichen Prostata-spezifisches Antigen (PSA), um spezifische und robuste Ausdruck der Gl&uuml;hw&uuml;rmchen Luciferase in die Prostata-Dr&uuml;sen des transgenen M&auml;usen zu erreichen. Ex Vivo best&auml;tigt Biolumineszenz-Darstellung und Analyse von in situ-Hybridisierung wurde, dass Luciferase-Ausdruck auf das Epithel in allen vier Lappen der Prostata beschr&auml;nkt. Wir zeigen auch, dass PSA-Luc M&auml;use zeigen verminderte aber leicht erkennbare Stufen der in-vivo Biolumineszenz &uuml;ber l&auml;ngere Zeitr&auml;ume nach Androgen-Ablation. Diese Ergebnisse legen nahe, dass dieser Reporter in-vivo Bildgebung der beiden Androgen-abh&auml;ngigen und Androgen-unabh&auml;ngigen Prostatakrebs Tumor-Modelle erm&ouml;glichen soll. Als Beweis-des-Prinzip zeigen wir, dass wir Bauteilqualit&auml;t SV40 T Antigen-induzierte Prostata Tumorentstehung bei M&auml;usen mit PSA-Luc Bild k&ouml;nnte. Dar&uuml;ber hinaus zeigen wir, dass unsere nichtinvasiven bildgebenden Strategie k&ouml;nnen erfolgreich zum Bild-Tumor-Antwort auf Androgen-Ablation in transgenen M&auml;usen und, als Folge, dass wir f&auml;hig dauerhaftes Tumorwachstum in Ermangelung von Androgenen einzelner Tiere schnell identifizieren k&ouml;nnen.

Nicht-invasive Biolumineszenz imaging, normal und spontan verwandelt Prostatagewebe bei M&auml;usen.

The purpose of this study was to investigate excess post-exercise oxygen consumption (EPOC) following a continuous 30 min bout of upper-body exercise (UBE) compared with 3 consecutive 10 min bouts of UBE. Ten male subjects (age (mean +/- standard deviation), 25.7 +/- 5.83 years; arm VO(2) (peak), 2.2 +/- 0.25 L x min(-1), on separate days (48 h between trials) and in counterbalanced order, performed a continuous 30 min bout of arm exercise at 60% of arm VO2 peak and 3 separate 10 min bouts of arm exercise at 60% of arm VO(2) (peak). Subjects reported to the laboratory rested and after a 12 h fast. Each test was preceded by a 30 min baseline test to determine resting metabolic rate. Post-exercise VO2 was continuously monitored until baseline was re-established. Results showed that the combined magnitude of the EPOCs from the intermittent exercise sessions was significantly (p > .05) greater (4.47 +/- 1.58 L O2) than that elicited from the continuous exercise session (1.54 +/- 1.25 L O2). These data indicate that separating a continuous 30 min arm exercise into 3 equal 10 min arm exercises will elicit a small but significantly higher EPOC, and thus result in greater post-exercise energy expenditure. This could be beneficial for those unable to perform lower-body exercise (LBE), or for those with limited exercise capacities.

Excess post-exercise oxygen consumption in untrained males: effects of intermittent durations of arm ergometry.

Der Zweck dieser Studie war excess Post-Exercise Oxygen Consumption (EPOC) Folgendes untersuchen eine kontinuierlichen 30 min-Anfall von Oberk&ouml;rper &Uuml;bung (UBE) mit 3 aufeinander folgenden 10 min Anf&auml;lle von UBE verglichen. Zehn m&auml;nnlichen Probanden (Alter (Mittelwert +/-Standardabweichung), 25,7 +/-5.83 Jahre; Arm VO(2) (Peak), 2.2 +/-0,25 L x min(-1), an unterschiedlichen Tagen (48 h zwischen Studien) und in Gegengewichtsstapler Reihenfolge, durchgef&uuml;hrt eine kontinuierlichen 30 min-Anfall von Hebelarm &Uuml;bung bei 60 % der Arm VO2 Peak und 3 separate 10Min Anf&auml;lle von Hebelarm &Uuml;bung bei 60 % der Arm VO(2) (Spitze). Themen berichtet im Labor ausgeruht und nach einem schnellen 12 h. Jeder Test war ein 30 min Grundlinie Pr&uuml;fung zur Bestimmung der Stoffwechselrate im Ruhezustand vorangestellt. Post-Exercise VO2 wurde kontinuierlich &uuml;berwacht, bis Grundlinie wieder hergestellt war. Ergebnisse zeigten, dass die kombinierte Gr&ouml;&szlig;e der EPOCs aus der intermittierenden Trainingseinheiten signifikant war (p &gt;.05) gr&ouml;&szlig;er (4.47 +/-1,58 L O2) als die aus dem die kontinuierliche Trainingseinheit (1,54 +/-1,25 L O2). Diese Daten zeigen, dass die Trennung einer kontinuierlichen 30 min Arm Bewegung in 3 gleich 10 min-Arm-&Uuml;bungen wird eine kleine, aber deutlich h&ouml;here EPOC zu entlocken und somit gr&ouml;&szlig;ere Post-Exercise Energieaufwand. Dies k&ouml;nnte n&uuml;tzlich f&uuml;r diejenigen, die nicht in der Lage, unteren K&ouml;rper-&Uuml;bung (LBE) auszuf&uuml;hren, oder f&uuml;r diejenigen mit begrenzten &Uuml;bung Kapazit&auml;ten.

Excess post-exercise Sauerstoffverbrauch bei untrainierten M&auml;nnern: Auswirkungen der intermittierenden Arm Ergometrie-dauern.

We have generated an EL1-luc/TAg transgenic mouse model that develops spontaneous and bioluminescent acinar cell carcinomas. We applied this model to noninvasively monitor tumor development and drug response.

A spontaneous acinar cell carcinoma model for monitoring progression of pancreatic lesions and response to treatment through noninvasive bioluminescence imaging.

Wir haben eine transgenen Mausmodell EL1-Luc/TAg generiert, die spontane und phosphoreszierende Azinus Zell Karzinomen entwickelt. Wir verwendet dieses Modell um Tumor Entwicklung und Ansprechens Bauteilqualit&auml;t zu &uuml;berwachen.

Eine spontane Azinus Zellen Karzinom Modell zur &Uuml;berwachung der Verlauf von Bauchspeicheldr&uuml;senkrebs L&auml;sionen und ansprechen auf die Behandlung durch nicht-invasive Biolumineszenz Bildgebung.

Bioluminescent imaging (BLI) is a non-invasive imaging modality widely used in the field of pre-clinical oncology research. Imaging of small animal tumour models using BLI involves the generation of light by luciferase-expressing cells in the animal following administration of substrate. This light may be imaged using an external detector. The technique allows a variety of tumour-associated properties to be visualized dynamically in living models. The increasing use of BLI as a small-animal imaging modality has led to advances in the development of xenogeneic, orthotopic, and genetically engineered animal models expressing luciferase genes. This review aims to provide insight into the principles of BLI and its applications in cancer research. Many studies to assess tumour growth and development, as well as efficacy of candidate therapeutics, have been performed using BLI. More recently, advances have also been made using bioluminescent imaging in studies of protein-protein interactions, genetic screening, cell-cycle regulators, and spontaneous cancer development. Such novel studies highlight the versatility and potential of bioluminescent imaging in future oncological research.

Bioluminescent imaging: a critical tool in pre-clinical oncology research.

Phosphoreszierende Imaging (BLI) ist eine nicht-invasive bildgebende Modalit&auml;t weit verbreitet im Bereich der pr&auml;klinischen Onkologie-Forschung. Bildgebung der kleinen tierischen Tumor-Modelle mit BLI umfasst die Erzeugung von Licht durch Luciferase-Ausdruck Zellen in der tierischen folgende Substrat. Dieses Licht kann mit einem externen Detektor abgebildet werden. Die Technik erm&ouml;glicht eine Vielzahl von Tumor-assoziierten Eigenschaften dynamisch in lebendigen Vorbildern visualisiert werden. Der zunehmende Einsatz von BLI als eine kleine Tier bildgebenden Modalit&auml;t f&uuml;hrte zu Fortschritten in der Entwicklung von xenogeneic, Orthotopic und gentechnisch ver&auml;nderte Tier Modelle auszudr&uuml;cken Luciferase-gen. Diese Bewertung soll einen Einblick in die Grunds&auml;tze der BLI und ihre Anwendungen in der Krebsforschung. Viele Studien beurteilen Tumorwachstum sowie Entwicklung und Wirksamkeit von Kandidaten-Therapeutika, wurden mit BLI durchgef&uuml;hrt. Vor kurzem haben auch Fortschritte mit phosphoreszierende Bildgebung in Studien von Protein-Protein Interaktionen, genetisches Screening, Zellzyklus Regulatoren und spontane Krebs-Entwicklung. Diese neuartigen Untersuchungen unterstreichen die Vielseitigkeit und das Potenzial der phosphoreszierende Bildgebung in Zukunft onkologische Forschung.

Phosphoreszierende Bildgebung: ein wichtiges Werkzeug in der pr&auml;klinischen Onkologie-Forschung.

Methods of assessing exercise-induced lymphocyte apoptosis have produced varying results. While morphological methods generally yield a significantly greater apoptotic index compared to those employing biochemical markers, benefits and limitations are associated with each methodology. Of interest in this report is the limitation of subjectivity associated with the morphological technique. To overcome the lack of objectivity associated with the morphological method, we describe an image-based approach by which computer software assesses the characteristics associated with lymphocyte apoptosis. A stochastic controlled deformable model can be employed to detect the classic morphological apoptotic changes induced by exercise, including membrane blebbing and the formation of apoptotic bodies. We propose that an objective evaluation of multiple points in the apoptotic process through the proposed model in conjunction with current biomarker methods has the potential to advance our understanding of the exercise-induced immune cell death response to a greater degree than current methods.

Exercise-induced immune cell apoptosis: image-based model for morphological assessment.

Methoden zur Bewertung von Lymphozyte Exercise-induced Apoptosis haben unterschiedliche Ergebnisse erbracht. W&auml;hrend morphologische Methoden im Allgemeinen einen wesentlich gr&ouml;&szlig;eren Apoptotic-Index im Vergleich zu den biochemische Markern besch&auml;ftigen ergeben, sind vor- und Nachteile jeder Methode zugeordnet. Interessant in diesem Bericht ist die Einschr&auml;nkung der Subjektivit&auml;t, die morphologische Technik zugeordnet. Um die mangelnde Objektivit&auml;t der morphologischen Methode zugeordnet zu &uuml;berwinden, beschreiben wir einen Image-basierte Ansatz, von welchem, den Computer Software Lymphozyte Apoptosis zugeordneten Merkmale beurteilt. Ein stochastischer kontrollierten verformbaren Modell kann eingesetzt werden, um die klassische morphologische apoptotischen Ver&auml;nderungen induziert durch &Uuml;bung, einschlie&szlig;lich Membrane Blebbing und die Bildung von Apoptotic K&ouml;rper zu erkennen. Wir schlagen vor, eine objektive Bewertung der verschiedenen Punkten in den apoptotischen Prozess &uuml;ber das vorgeschlagene Modell in Verbindung mit aktuellen Biomarker-Methoden das Potenzial hat, unser Verst&auml;ndnis von der Exercise-induced immun Zellselbstmord verst&auml;rkt als aktuelle Methoden zu f&ouml;rdern.

Immunzellen Exercise-induced Apoptosis: Image-basierte Modell f&uuml;r morphologische Bewertung.

The International Journal of Exercise Science is the only student-centered peer-reviewed journal in its field. Upon graduate student first author submissions, two student reviewers and one faculty reviewer are asked to review. On professionally submitted papers, two faculty peers are asked to assess the manuscript. The purpose of the present study was to determine whether graduate students returned similar decisions compared with faculty reviewers who evaluated the same manuscript. In addition, decisions of faculty peers reviewing graduate student- versus faculty-submitted manuscripts were compared. Mean comparisons between groups were evaluated using independent t-tests with significance at P â‰¤ 0.05. Graduate students (2.21 Â± 0.69) and faculty peers (2.24 Â± 0.66) returned similar decisions on student-submitted manuscripts (P = 0.84). Faculty decisions on manuscripts submitted by a professional primary author (1.86 Â± 0.77) were not different compared with faculty peers reviewing student manuscripts (P = 0.06). Statistics revealed that graduate students are just as stringent in the peer review process as established reviewers. Additionally, faculty reviewers evaluated manuscripts equally regardless of submission type.

Student peer review decisions on submitted manuscripts are as stringent as faculty peer reviewers.

International Journal of Exercise Science ist die nur Studenten-zentrierte Peer-Review-Zeitschrift auf seinem Gebiet. Nach Erstautor Schulabg&auml;nger sind Einreichungen, zwei Studenten Bewertungen und einer Fakult&auml;t Reviewer gebeten, &uuml;berpr&uuml;fen. Auf professionell eingereichten Beitr&auml;gen werden zwei Fakult&auml;t Peers gefragt, um das Manuskript zu bewerten. Der Zweck der vorliegenden Studie war festzustellen, ob Doktoranden zur&uuml;ckgegeben &auml;hnliche Entscheidungen gegen&uuml;ber Fakult&auml;t-Pr&uuml;fer, die derselben Handschrift ausgewertet. Dar&uuml;ber hinaus wurden die Entscheidungen der Fakult&auml;t Peers &Uuml;berpr&uuml;fung graduate Student-gegen&uuml;ber Fakult&auml;t eingereichte Manuskripte verglichen. Mittlere Vergleiche zwischen Gruppen wurden mit unabh&auml;ngigen t-Tests mit Bedeutung bei P &le; 0,05 ausgewertet. Doktoranden (2.21 &plusmn; 0,69) und Fakult&auml;t Peers (2.24 &plusmn; 0,66) &auml;hnliche Entscheidungen auf Student eingereichte Manuskripte zur&uuml;ckgegeben (P = 0,84). Fakult&auml;t f&uuml;r Entscheidungen &uuml;ber Manuskripte Verfasst von einem professionellen Hauptautor (1,86 &plusmn; 0,77) waren nicht anders gegen&uuml;ber Fakult&auml;t Kollegen &uuml;berpr&uuml;fen Student Manuskripte (P = 0,06). Statistiken gezeigt, dass Studenten nur so streng in den Peer-Review-Prozess als etablierte Bewertungen. Dar&uuml;ber hinaus bewertet Fakult&auml;t Bewertungen Handschriften ebenso unabh&auml;ngig von der Art der Vorlage.

Student Peer Review Entscheidungen &uuml;ber eingereichte Manuskripte sind genauso streng wie Fakult&auml;t Gutachter.

The purpose of this investigation was to determine whether cognitive awareness of carbohydrate beverage consumption affects exercise-induced lymphocyte apoptosis, independent of actual carbohydrate intake.

Cognitive awareness of carbohydrate intake does not alter exercise-induced lymphocyte apoptosis.

Ziel dieser Untersuchung war zu ermitteln, ob kognitive Bewusstsein der Kohlenhydrat-Getr&auml;nk-Verbrauch Lymphozyte Exercise-induced Apoptosis, unabh&auml;ngig vom tats&auml;chlichen Kohlenhydrat-Aufnahme betrifft.

Kognitive Bewusstsein der Kohlenhydrat-Aufnahme ver&auml;ndert nicht Lymphozyte Exercise-induced Apoptosis.

Cell surface glycans are involved in numerous physiological processes that involve cell-cell interactions and migration, including lymphocyte trafficking and cancer metastasis. We have used a bioorthogonal metabolic labeling strategy to detect cell surface glycans and demonstrate, for the first time, fluorescence and radionuclide imaging of sialylated glycans in a murine tumor model in vivo. Peracetylated azido-labeled N-acetyl-mannosamine, injected intraperitoneally, was used as the metabolic precursor for the biosynthesis of 5-azidoneuraminic, or azidosialic acid. Azidosialic acid-labeled cell surface glycans were then reacted, by Staudinger ligation, with a biotinylated phosphine injected intraperitoneally, and the biotin was detected by subsequent intravenous injection of a fluorescent or radiolabeled avidin derivative. At 24 h after administration of NeutrAvidin, labeled with either a far-red fluorophore or (111)In, there was a significant azido-labeled N-acetyl-mannosamine-dependent increase in tumor-to-tissue contrast, which was detected using optical imaging or single-photon-emission computed tomography (SPECT), respectively. The technique has the potential to translate to the clinic, where, given the prognostic relevance of altered sialic acid expression in cancer, it could be used to monitor disease progression.

Imaging sialylated tumor cell glycans in vivo.

Zelle Oberfl&auml;che Glykane sind zahlreiche physiologische Prozesse, bei denen Zell-Zell-Interaktionen und Migration, einschlie&szlig;lich des Handels mit Lymphozyten und Krebsmetastase beteiligt. Wir haben ein Bioorthogonal metabolische Kennzeichnung Strategie verwendet, um Zelle Oberfl&auml;che Glykane zu erkennen und zu demonstrieren, f&uuml;r die erste Zeit, Fluoreszenz und Radionuklid Bildgebung von Sialylated Glykane in einem murinen Tumor-Modell in-vivo. Peracetylated Azido-beschriftet N-Acetyl-Mannosamine, intraperitoneal, injiziert wurde als metabolische Vorl&auml;ufer f&uuml;r die Biosynthese von 5-Azidoneuraminic oder Azidosialic S&auml;ure verwendet. Azidosialic S&auml;ure-markierten Zelle Oberfl&auml;che Glykane wurden dann reagiert, von Staudinger Ligation, mit einem biotinylierten Phosphin intraperitoneal, injiziert und das Biotin durch nachfolgende intraven&ouml;se Injektion eines fluoreszierenden oder radioaktive Avidin-Derivats erkannt wurde. 24 H nach Verabreichung des NeutrAvidin, gekennzeichnet mit (111) oder eine dunkelrote Fluorophor, gab Azido-beschriftet N-Acetyl-Mannosamine-abh&auml;ngigen deutlich im Tumorgewebe-Kontrast, die mittels Bildgebung oder Single-Photon-Emissions-Computertomographie (SPECT), bzw. entdeckt wurde. Die Technik hat das Potential, in die Klinik, zu &uuml;bersetzen, wo die prognostische Relevanz der ver&auml;nderten Sialins&auml;ure Ausdruck in Krebs gegeben, damit man k&ouml;nnte Fortschreiten der Krankheit zu &uuml;berwachen.

Sialylated Tumor Zelle Glykane in-vivo Imaging.

The androgen receptor (AR) is a key regulator of prostate growth and the principal drug target for the treatment of prostate cancer. Previous studies have mapped AR targets and identified some candidates which may contribute to cancer progression, but did not characterize AR biology in an integrated manner. In this study, we took an interdisciplinary approach, integrating detailed genomic studies with metabolomic profiling and identify an anabolic transcriptional network involving AR as the core regulator. Restricting flux through anabolic pathways is an attractive approach to deprive tumours of the building blocks needed to sustain tumour growth. Therefore, we searched for targets of the AR that may contribute to these anabolic processes and could be amenable to therapeutic intervention by virtue of differential expression in prostate tumours. This highlighted calcium/calmodulin-dependent protein kinase kinase 2, which we show is overexpressed in prostate cancer and regulates cancer cell growth via its unexpected role as a hormone-dependent modulator of anabolic metabolism. In conclusion, it is possible to progress from transcriptional studies to a promising therapeutic target by taking an unbiased interdisciplinary approach.

The androgen receptor fuels prostate cancer by regulating central metabolism and biosynthesis.

Der Androgenrezeptor (AR) ist ein wichtiger Regulator der Prostata Wachstum und das wichtigste Medikament Ziel f&uuml;r die Behandlung von Prostatakrebs. Fr&uuml;here Studien haben AR Ziele zugeordnet und identifiziert einige Kandidaten die k&ouml;nnen dazu beitragen, fortschreiten, aber nicht AR Biologie in einer integrierten Weise charakterisieren. In dieser Studie wir nahmen einen interdisziplin&auml;ren Ansatz, Integration von genomische Detailstudien mit metabolische Profilerstellung und identifizieren eine anabole transkriptionelle Netzwerk AR als der Kern-Regler. Fluss durch anabole Wege einschr&auml;nken, ist ein attraktiver Ansatz, Tumore der Tumorwachstum Aufrechterhaltung notwendig Bausteine zu berauben. Daher suchten wir Ziele der AR, die kann dazu beitragen, diese anabole Prozesse und k&ouml;nnte geneigt sein, therapeutische Intervention aufgrund differenzieller Ausdruck in Prostata-Tumoren. Setzt sich mit Calcium/Calmodulin-abh&auml;ngige Kinase Proteinkinase 2, die wir zeigen ist Prostatakrebs Pleuramesotheliom und Krebs-Zellwachstum &uuml;ber ihre unerwartete Rolle als Hormon-abh&auml;ngigen Modulator von anabolen Stoffwechsel reguliert. Abschlie&szlig;end ist es m&ouml;glich den Fortschritt von transkriptionelle Studien zu einem viel versprechenden therapeutischen Ziel durch einen unvoreingenommenen interdisziplin&auml;ren Ansatz.

Article	Year
Noninvasive imaging of spontaneous retinoblastoma pathway-dependent tumors in mice. Cancer research\| PubMed ID: 11912166	2002
The generation of a conditional reporter that enables bioluminescence imaging of Cre/loxP-dependent tumorigenesis in mice. Cancer research\| PubMed ID: 14612492	2003
Spatial statistical analysis of adult mosquito (Diptera: Culicidae) counts: an example using light trap data, in Redland Shire, Southeastern Queensland, Australia. Journal of medical entomology\| PubMed ID: 15605654	2004
Advances in imaging mouse tumour models in vivo. The Journal of pathology\| PubMed ID: 15641018	2005
Noninvasive bioluminescence imaging of normal and spontaneously transformed prostate tissue in mice. Cancer research\| PubMed ID: 16651422	2006
Excess post-exercise oxygen consumption in untrained males: effects of intermittent durations of arm ergometry. Applied physiology, nutrition, and metabolism = Physiologie appliquÃ©e, nutrition et mÃ©tabolisme\| PubMed ID: 16770345	2006
A spontaneous acinar cell carcinoma model for monitoring progression of pancreatic lesions and response to treatment through noninvasive bioluminescence imaging. Clinical cancer research : an official journal of the American Association for Cancer Research\| PubMed ID: 19622581	2009
Bioluminescent imaging: a critical tool in pre-clinical oncology research. The Journal of pathology\| PubMed ID: 19967724	2010
Exercise-induced immune cell apoptosis: image-based model for morphological assessment. European journal of applied physiology\| PubMed ID: 20490823	2010
Student peer review decisions on submitted manuscripts are as stringent as faculty peer reviewers. Advances in physiology education\| PubMed ID: 21098383	2010
Cognitive awareness of carbohydrate intake does not alter exercise-induced lymphocyte apoptosis. Clinics (SÃ£o Paulo, Brazil)\| PubMed ID: 21484033	2011
Imaging sialylated tumor cell glycans in vivo. FASEB journal : official publication of the Federation of American Societies for Experimental Biology\| PubMed ID: 21493886	2011
The androgen receptor fuels prostate cancer by regulating central metabolism and biosynthesis. The EMBO journal\| PubMed ID: 21602788	2011

Scott Lyons

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JoVE Journal Publications

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