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[en] The urokinase plasminogen activator system (uPA, uPAR, PAI-1) is upregulated in cancer and high plasma levels are associated with poor prognosis. Their interaction with hypoxia-related osteopontin (OPN) which is also overexpressed in malignant tumors suggests potential clinical relevance. However, the prognostic role of the uPA system in the radiotherapy (RT) of non-small-cell lung cancer (NSCLC), particularly in combination with OPN, has not been investigated so far. uPA, uPAR, PAI-1 and OPN plasma levels of 81 patients with locally advanced or metastasized NSCLC were prospectively analyzed by ELISA before RT and were correlated to clinical patient/tumor data and prognosis after RT. uPAR plasma levels were higher in M1; uPA and PAI-1 levels were higher in M0 NSCLC patients. uPAR correlated with uPA (p < 0.001) which also correlated with PAI-1 (p < 0.001). The prognostic impact of OPN plasma levels in the RT of NSCLC was previously reported by our group. PAI-I plasma levels significantly impacted overall (OS) and progression-free survival (PFS). Low PAI-1 levels were associated with a significantly reduced OS and PFS with a nearly 2-fold increased risk of death (p = 0.029) and tumor progression (p = 0.029). In multivariate analysis, PAI-1 levels remained an independent prognostic factor for OS and PFS with a 3-fold increased risk of death (p = 0.001). If PAI-1 plasma levels were combined with OPN or tumor volume, we found an additive prognostic impact on OS and PFS with a 2.5- to 3-fold increased risk of death (p = 0.01). Our results suggest that PAI-1 but not uPA and uPAR might add prognostic information in patients with advanced NSCLC undergoing RT. High pretreatment PAI-1 plasma levels were found predominantly in M0-stage patients and indicate a favorable prognosis as opposed to OPN where high plasma levels are associated with poor survival and metastasis. In combination, PAI-1 and OPN levels successfully predicted outcome and additively correlated with prognosis. These findings support the notion of an antidromic prognostic impact of OPN and PAI-1 plasma levels in the RT of advanced NSCLC. (orig.)
[de]
Das Urokinase-Plasminogen-Aktivator-System (uPA, uPAR, PAI-1) ist in malignen Tumoren hochreguliert und hohe Plasmaspiegel mit schlechter Prognose assoziiert. Deren Zusammenspiel mit hypoxieassoziierten Proteinen wie Osteopontin (OPN), welches ebenfalls in malignen Tumoren ueberexprimiert ist, legt eine potenzielle klinische Relevanz nahe. Die prognostische Bedeutung des uPA-Systems fuer die RT des NSCLC (''non-small-cell lung cancer''), insbesondere in Kombination mit OPN, wurde bisher noch nicht untersucht. Bei 81 Patienten mit lokal fortgeschrittenem bzw. metastasiertem NSCLC wurden Plasmaspiegel von uPA, uPAR, PAI-1 und OPN vor RT prospektiv mittels ELISA bestimmt und mit klinischen Patienten- und Tumorparametern sowie der Prognose nach RT korreliert. uPAR-Plasmalevel waren bei M1-Patienten hoeher; uPA- und PAI-1-Plasmaspiegel waren bei nichtmetastasierten Patienten (M0) erhoeht. uPAR korrelierte mit uPA (p < 0,001), das ebenfalls mit PAI-1 korrelierte (p < 0,001). Der prognostische Effekt von OPN-Plasmaspiegeln in der RT von NSCLC wurde bereits in unseren Vorarbeiten gezeigt. PAI-1-Plasmaspiegel korrelierten signifikant mit Gesamtueberleben (OS) und progressionsfreiem Ueberleben (PFS). Niedrige PAI-1-Spiegel waren mit reduziertem OS und PFS verbunden sowie mit einem fast 2-fach erhoehtem Risiko zu versterben (p = 0,029) bzw. einen Tumorprogress im Verlauf zu erleiden (p = 0,029). In der multivariaten Analyse zeigten sich PAI-1-Plasmaspiegel als unabhaengiger prognostischer Marker fuer OS und PFS, wobei bei erhoehten PAI-1-Spiegeln ein 3-fach erhoehtes Risiko zu versterben vorlag (p = 0,001). Bei der Kombination von PAI-1 mit OPN-Plasmaspiegeln bzw. Tumorvolumen zeigte sich ein additiver prognostischer Effekt fuer OS und PFS sowie ein 2,5- bis 3-fach erhoehtes Risiko zu versterben (p = 0,01). Die Ergebnisse zeigen, dass PAI-1-Plasmaspiegel im Gegensatz zu uPA- bzw. uPAR-Plasmaspiegeln zusaetzliche prognostisch relevante Informationen fuer die RT beim fortgeschrittenen NSCLC liefern koennten. Hohe praetherapeutische PAI-1-Plasmaspiegel liegen v. a. bei nichtmetastasierten Patienten vor und zeigen eine guenstige Prognose an - im Gegensatz zu hohen OPN-Plasmaspiegeln, die mit reduziertem OS nach RT und Metastasierung assoziiert sind. In der Kombination mit OPN praedizierten PAI-1-Plasmaspiegel erfolgreich das prognostische Outcome nach RT. Die Resultate sprechen fuer eine differenzielle prognostische Bedeutung von OPN- und PAI-1-Plasmaspiegeln bei der RT des fortgeschrittenen NSCLC. (orig.)Journal
[en] We study the spatial correlations of quantum fluctuations that can be observed in multimode parametric down-conversion in the regime of high gain. We investigate both a type-I and a type-II phase-matching configuration: in the latter case spatial correlations at the quantum level are shown to exist both in the near-field and in the far-field zones of the down-converted light. In the stationary and plane-wave approximation we treat the problem analytically. A stochastic model is solved numerically to obtain quantitative results beyond this approximation. The finite transverse size and pulse duration of the pump beam and other features of the system, such as spatial walk-off and diffraction are taken into account, and we show that correlations beyond the standard quantum limit exist for values of parameters consistent with realistic experiments
Journal
[en] We present a theoretical study of ghost imaging based on correlated beams arising from parametric down-conversion, and which uses balanced homodyne detection to measure both the signal and idler fields. We analytically show that the signal-idler correlations contain the full amplitude and phase information about an object located in the signal path, both in the near-field and the far-field case. To this end we discuss how to optimize the optical setups in the two imaging paths, including the crucial point regarding how to engineer the phase of the idler local oscillator as to observe the desired orthogonal quadrature components of the image. As is well known, the near-field image resolution is inherently linked to the far-field bandwidth of the image, determined by the bandwidth of the source of the correlated beams. We show how to circumvent this limitation by using a spatial averaging technique which dramatically improves the imaging bandwidth of the far-field correlations as well as speeds up the convergence rate. The results are backed up by numerical simulations taking into account the finite size and duration of the pump pulse
Journal
[en] We analytically show that it is possible to perform coherent imaging by using the classical correlation of two beams obtained by splitting incoherent thermal radiation. A formal analogy is demonstrated between two such classically correlated beams and two entangled beams produced by parametric down-conversion. Because of this analogy, the classical beams can mimic qualitatively all the imaging properties of the entangled beams, even in ways which up to now were not believed possible. A key feature is that these classical beams are spatially correlated both in the near field and in the far field. Using realistic numerical simulations the performances of a quasithermal and a parametric down-conversion source are shown to be closely similar, both for what concerns the resolution and statistical properties. The results of this paper provide a scenario for the discussion of what role the entanglement plays in correlated imaging
Journal
[en] By using the ghost imaging technique, we experimentally demonstrate the reconstruction of the diffraction pattern of a pure phase object by using the classical correlation of incoherent thermal light split on a beam splitter. The results once again underline that entanglement is not a necessary feature of ghost imaging. The light we use is spatially highly incoherent with respect to the object (≅2 μm speckle size) and is produced by a pseudo-thermal source relying on the principle of near-field scattering. We show that in these conditions no information on the phase object can be retrieved by only measuring the light that passed through it, neither in a direct measurement nor in a Hanbury Brown-Twiss (HBT) scheme. In general, we show a remarkable complementarity between ghost imaging and the HBT scheme when dealing with a phase object
Journal
[en] In summary it can be said that sodium peroxodisulphate effectively inhibits tumour cell growth and adds to the effect of single irradiations. On account of its oxidising properties sodium peroxodisulphate appears particularly suitable for use in hypoxic tumours. How sodium peroxodisulphate acts under severely hypoxic conditions remains to be determined by further experimentation
[de]
Zusammenfassend laesst sich feststellen, dass Natriumperoxodisulfat das Tumorzellwachstum effektiv hemmt bzw. die Effekte einer Einzelbestrahlung additiv verstaerkt. Aufgrund seiner oxidierenden Eigenschaften scheint Natriumperoxodisulfat insbesondere fuer den Einsatz in hypoxischen Tumoren als geeignet. In weiterfuehrenden Experimenten muss jedoch die Wirkung von Natriumperoxodisulfat unter stark hypoxischen Bedingungen getestet werden. (orig.)Source
Baumann, M.; Raabe, A.; Petersen, C.; Technische Univ. Dresden (Germany). Klinik und Poliklinik fuer Strahlentherapie und Radioonkologie; 140 p; ISSN 1432-864X; 
; 2004; p. 23-27; 13. symposium on experimental radiotherapy and clinical radiobiology; 13. Symposium Experimentelle Strahlentherapie und Klinische Strahlenbiologie; Dresden (Germany); 4-6 Mar 2004; Available from TIB Hannover
; 2004; p. 23-27; 13. symposium on experimental radiotherapy and clinical radiobiology; 13. Symposium Experimentelle Strahlentherapie und Klinische Strahlenbiologie; Dresden (Germany); 4-6 Mar 2004; Available from TIB Hannover
[en] Hypoxic radioresistance plays a critical role in the radiotherapy of cancer and adversely impacts prognosis and treatment response. This prospective study investigated the interrelationship and the prognostic significance of several hypoxia-related proteins in non-small cell lung cancer (NSCLC) patients treated by radiotherapy ± chemotherapy. Pretreatment osteopontin (OPN), vascular endothelial growth factor (VEGF) and carbonic anhydrase IX (CA IX) plasma levels were determined by ELISA in 55 NSCLC (M0) patients receiving 66 Gy curative-intent radiotherapy or chemoradiation. Marker correlation, association with clinicopathological parameters and the prognostic value of a biomarker combination was evaluated. All biomarkers were linearly correlated and linked to different clinical parameters including lung function, weight loss (OPN), gross tumor volume (VEGF) and T stage (CA IX). High OPN (p = 0.03), VEGF (p = 0.02) and CA IX (p = 0.04) values were significantly associated with poor survival. Double marker combination additively increased the risk of death by a factor of 2 and high plasma levels of the triple combination OPN/VEGF/CA IX yielded a 5.9-fold risk of death (p = 0.009). The combined assessment of OPN/VEGF/CA IX correlated independently with prognosis (p = 0.03) in a multivariate Cox regression model including N stage, T stage and GTV. This pilot study suggests that a co-detection augments the prognostic value of single markers and that the integration of OPN, VEGF and CA IX into a hypoxic biomarker profile for the identification of patients with largely hypoxic and radioresistant tumors should be further evaluated. (orig.)
[de]
Hypoxische Radioresistenz spielt eine kritische Rolle in der Radiotherapie maligner Tumoren und beeinflusst Prognose und Therapieansprechen negativ. Diese prospektive Studie untersuchte den Zusammenhang und die prognostische Bedeutung einiger hypoxieassoziierter Proteine bei Patienten mit nicht-kleinzelligem Bronchialkarzinom (NSCLC), welche mit Radiotherapie ± Chemotherapie behandelt wurden. Praetherapeutische Plasmaspiegel von Osteopontin (OPN), vaskulaerem endothelialem Wachstumsfaktor (VEGF) und Carboanhydrase IX (CA IX) wurden in 55 NSCLC-Patienten (M0), welche eine kurativ intendierte Radiotherapie mit 66 Gy oder Radiochemotherapie erhielten, mittels ELISA bestimmt. Es wurden Markerkorrelation, der Zusammenhang mit klinisch-pathologischen Parametern und die prognostische Bedeutung einer Markerkombination evaluiert. Alle Biomarker korrelierten untereinander linear und waren mit unterschiedlichen klinischen Parametern wie Lungenfunktion (OPN), Tumorvolumen (VEGF) und T-Stadium (CA IX) assoziiert. Hohe OPN- (p = 0,03), VEGF- (p = 0,02) und CA-IX-Plasmaspiegel (p = 0,04) waren signifikant mit einem verkuerztem Gesamtueberleben vergesellschaftet. Eine Zweierkombination der Marker verdoppelte additiv das Risiko, zu versterben, und hohe Plasmalevel der Dreierkombination OPN/VEGF/CA IX ergaben ein 5,9-fach erhoehtes Risiko, zu versterben (p = 0,009). In einer multivariaten Analyse zeigte sich die Dreierkombination OPN/VEGF/CA IX als unabhaengiger Prognosefaktor (p = 0,03) neben N-, T-Stadium und GTV. Diese Pilotstudie zeigt, dass eine Kodetektion die prognostische Aussagekraft einzelner Biomarker erhoeht bzw. die Integration von OPN, VEGF und CA IX in ein ''hypoxisches Biomarkerprofil'' zur Identifizierung von Patienten mit hypoxischen bzw. radioresistenten Tumoren weiter geprueft werden sollte. (orig.)Journal
No abstract available
Source
Baumann, Michael; Dahm-Daphi, Jochen; Dikomey, Ekkehard; Petersen, Cordula; Rodemann, H. Peter; Zips, Daniel (eds.); Universitaetsklinikum Carl Gustav Carus Dresden - Technische Univ. Dresden (Germany). Klinik und Poliklinik fuer Strahlentherapie und Radioonkologie; 157 p; ISSN 1432-864X; ; 2009; p. 39-43; 18. symposium on experimental radiotherapy and clinical radiobiology; 18. Symposium 'Experimentelle Strahlentherapie und Klinische Strahlenbiologie'; Dresden (Germany); 26-28 Feb 2009; GRANT FKZ 2007.123.1; Country of input: International Atomic Energy Agency (IAEA); 7 refs, 6 figs
; 2009; p. 39-43; 18. symposium on experimental radiotherapy and clinical radiobiology; 18. Symposium 'Experimentelle Strahlentherapie und Klinische Strahlenbiologie'; Dresden (Germany); 26-28 Feb 2009; GRANT FKZ 2007.123.1; Country of input: International Atomic Energy Agency (IAEA); 7 refs, 6 figs
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