TY  - JOUR
A1  - Lüftner, Daniel
A1  - Milko, Matus
A1  - Huppmann, Sophia
A1  - Scholz, Markus
A1  - Ngyuen, Nam
A1  - Wießner, Michael
A1  - Schöll, Achim
A1  - Reinert, Friedrich
A1  - Puschnig, Peter
T1  - CuPc/Au(1 1 0): Determination of the azimuthal alignment by a combination of angle-resolved photoemission and density functional theory
JF  - Journal of Electron Spectroscopy and Related Phenomena
N2  - Here we report on a combined experimental and theoretical study on the structural and electronic properties of a monolayer of Copper-Phthalocyanine (CuPc) on the Au(1 1 0) surface. Low-energy electron diffraction reveals a commensurate overlayer unit cell containing one adsorbate species. The azimuthal alignment of the CuPc molecule is revealed by comparing experimental constant binding energy (kxky)-maps using angle-resolved photoelectron spectroscopy with theoretical momentum maps of the free molecule's highest occupied molecular orbital (HOMO). This structural information is confirmed by total energy calculations within the framework of van-der-Waals corrected density functional theory. The electronic structure is further analyzed by computing the molecule-projected density of states, using both a semi-local and a hybrid exchange-correlation functional. In agreement with experiment, the HOMO is located about 1.2 eV below the Fermi-level, while there is no significant charge transfer into the molecule and the CuPc LUMO remains unoccupied on the Au(1 1 0) surface.
KW  - density functional theory
KW  - angle-resolved photoemission spectroscopy
KW  - organic molecule
KW  - organic–metal interface
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-120986
SN  - 0368-2048
VL  - 195
ER  - 
TY  - JOUR
A1  - Harter, Patrick N.
A1  - Bernatz, Simon
A1  - Scholz, Alexander
A1  - Zeiner, Pia S.
A1  - Zinke, Jenny
A1  - Kiyose, Makoto
A1  - Blasel, Stella
A1  - Beschorner, Rudi
A1  - Senft, Christian
A1  - Bender, Benjamin
A1  - Ronellenfitsch, Michael W.
A1  - Wikman, Harriet
A1  - Glatzel, Markus
A1  - Meinhardt, Matthias
A1  - Juratli, Tareq A.
A1  - Steinbach, Joachim P.
A1  - Plate, Karl H.
A1  - Wischhusen, Jörg
A1  - Weide, Benjamin
A1  - Mittelbronn, Michel
T1  - Distribution and prognostic relevance of tumor-infiltrating lymphocytes (TILs) and PD-1/PD-L1 immune checkpoints in human brain metastases
JF  - Oncotarget
N2  - The activation of immune cells by targeting checkpoint inhibitors showed promising results with increased patient survival in distinct primary cancers. Since only limited data exist for human brain metastases, we aimed at characterizing tumor infiltrating lymphocytes (TILs) and expression of immune checkpoints in the respective tumors. Two brain metastases cohorts, a mixed entity cohort (n = 252) and a breast carcinoma validation cohort (n = 96) were analyzed for CD3+, CD8+, FOXP3+, PD-1+ lymphocytes and PD-L1+ tumor cells by immunohistochemistry. Analyses for association with clinico-epidemiological and neuroradiological parameters such as patient survival or tumor size were performed. TILs infiltrated brain metastases in three different patterns (stromal, peritumoral, diffuse). While carcinomas often show a strong stromal infiltration, TILs in melanomas often diffusely infiltrate the tumors. Highest levels of CD3+ and CD8+ lymphocytes were seen in renal cell carcinomas (RCC) and strongest PD-1 levels on RCCs and melanomas. High amounts of TILs, high ratios of PD-1+/CD8+ cells and high levels of PD-L1 were negatively correlated with brain metastases size, indicating that in smaller brain metastases CD8+ immune response might get blocked. PD-L1 expression strongly correlated with TILs and FOXP3 expression. No significant association of patient survival with TILs was observed, while high levels of PD-L1 showed a strong trend towards better survival in melanoma brain metastases (Log-Rank p = 0.0537). In summary, melanomas and RCCs seem to be the most immunogenic entities. Differences in immunotherapeutic response between tumor entities regarding brain metastases might be attributable to this finding and need further investigation in larger patient cohorts.
KW  - B7-H1
KW  - PD-L1
KW  - immunoresistance
KW  - immunosurveillance
KW  - safety
KW  - survival
KW  - expression
KW  - melanoma
KW  - breast cancer
KW  - PC-1 blockade
KW  - cell lung cancer
KW  - tumor-infiltrating lymphocytes
KW  - brain metastases
KW  - PD-1
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-137107
VL  - 6
IS  - 38
SP  - 40836
EP  - 40849
ER  - 
TY  - JOUR
A1  - Schubert, Maria
A1  - Joniau, Steven
A1  - Gontero, Paolo
A1  - Kneitz, Susanne
A1  - Scholz, Claus-Jürgen
A1  - Kneitz, Burkhard
A1  - Briganti, Alberto
A1  - Karnes, R. Jeffery
A1  - Tombal, Bertrand
A1  - Walz, Jochen
A1  - Hsu, Chao-Yu
A1  - Marchioro, Giansilvio
A1  - Bader, Pia
A1  - Bangma, Chris
A1  - Frohneberg, Detlef
A1  - Graefen, Markus
A1  - Schröder, Fritz
A1  - van Cangh, Paul
A1  - van Poppel, Hein
A1  - Spahn, Martin
T1  - The Role of Adjuvant Hormonal Treatment after Surgery for Localized High-Risk Prostate Cancer: Results of a Matched Multiinstitutional Analysis
JF  - Advances in Urology
N2  - Introduction. To assess the role of adjuvant androgen deprivation therapy (ADT) in high-risk prostate cancer patients (PCa) after surgery. Materials and Methods. The analysis case matched 172 high-risk PCa patients with positive section margins or non-organ confined disease and negative lymph nodes to receive adjuvant ADT (group 1, n=86 ) or no adjuvant ADT (group 2, n=86). Results. Only 11.6% of the patients died, 2.3% PCa related. Estimated 5–10-year clinical progression-free survival was 96.9% (94.3%) for group 1 and 73.7% (67.0%) for group 2, respectively. Subgroup analysis identified men with T2/T3a tumors at low-risk and T3b margins positive disease at higher risk for progression. Conclusion. Patients with T2/T3a tumors are at low-risk for metastatic disease and cancer-related death and do not need adjuvant ADT. We identified men with T3b margin positive disease at highest risk for clinical progression. These patients benefit from immediate adjuvant ADT.
KW  - prostate cancer
KW  - adjuvant hormonal treatment
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-137712
VL  - 2012
ER  - 
TY  - JOUR
A1  - Kneitz, Burkhard
A1  - Kalogirou, Charis
A1  - Spahn, Martin
A1  - Krebs, Markus
A1  - Joniau, Steven
A1  - Lerut, Evelyne
A1  - Burger, Maximilian
A1  - Scholz, Claus-Jürgen
A1  - Kneitz, Susanne
A1  - Riedmiller, Hubertus
T1  - MiR-205 Is Progressively Down-Regulated in Lymph Node Metastasis but Fails as a Prognostic Biomarker in High-Risk Prostate Cancer
JF  - International Journal of Molecular Sciences
N2  - The treatment of high-risk prostate cancer (HRPCa) is a tremendous challenge for uro-oncologists. The identification of predictive moleculobiological markers allowing risk assessment of lymph node metastasis and systemic progression is essential in establishing effective treatment. In the current study, we investigate the prognostic potential of miR-205 in HRPCa study and validation cohorts, setting defined clinical endpoints for both. We demonstrate miR-205 to be significantly down-regulated in over 70% of the HRPCa samples analysed and that reconstitution of miR-205 causes inhibition of proliferation and invasiveness in prostate cancer (PCa) cell lines. Additionally, miR-205 is increasingly down-regulated in lymph node metastases compared to the primary tumour indicating that miR-205 plays a role in migration of PCa cells from the original location into extraprostatic tissue. Nevertheless, down-regulation of miR-205 in primary PCa was not correlated to the synchronous presence of metastasis and failed to predict the outcome for HRPCa patients. Moreover, we found a tendency for miR-205 up-regulation to correlate with an adverse outcome of PCa patients suggesting a pivotal role of miR-205 in tumourigenesis. Overall, we showed that miR-205 is involved in the development and metastasis of PCa, but failed to work as a useful clinical biomarker in HRPCa. These findings might have implications for the use of miR-205 as a prognostic or therapeutic target in HRPCa.
KW  - high-risk prostate cancer
KW  - microRNA
KW  - miR-205
KW  - prognosis
KW  - biomarker
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-97321
ER  - 
TY  - THES
A1  - Scholz, Markus
T1  - Energy-Dispersive NEXAFS: A Novel Tool for the Investigation of Intermolecular Interaction and Structural Phase Dynamics
T1  - Energiedispersives NEXAFS: Eine neue Methode zur Untersuchung intermolekularer Wechselwirkung und Phasendynamik
N2  - In the context of this thesis, the novel method soft X-ray energy-dispersive NEXAFS spectroscopy was explored and utilized to investigate intermolecular coupling and post-growth processes with a temporal resolution of seconds. 1,4,5,8- naphthalene tetracarboxylic acid dianhydride (NTCDA)multilayer films were the chosen model system for these investigations. The core hole-electron correlation in coherently coupled molecules was studied by means of energy-dispersive near-edge X-ray absorption fine-structure spectroscopy. A transient phase was found which exists during the transition between a disordered condensed phase and the bulk structure. This phase is characterized by distinct changes in the spectral line shape and energetic position of the X-ray absorption signal at the C K-edge. The findings were explained with the help of theoretical models based on the coupling of transition dipole moments, which are well established for optically excited systems. In consequence, the experimental results provides evidence for a core hole-electron pair delocalized over several molecules. Furthermore, the structure formation of NTCDA multilayer films on Ag(111) surfaces was investigated. With time-resolved and energy-dispersive NEXAFS experiments the intensity evolution in s- and p-polarization showed a very characteristic behavior. By combining these findings with the results of time-dependent photoemission measurements, several sub-processes were identified in the post- growth behavior. Upon annealing, the amorphous but preferentially flat-lying molecules flip into an upright orientation. After that follows a phase characterized by strong intermolecular coupling. Finally, three-dimensional islands are established. Employing the Kolmogorov-Johnson-Mehl-Avrami model, the activation energies of the sub-processes were determined.
N2  - Im Rahmen dieser Arbeit wurden die Möglichkeiten der neuartigen Methode energiedispersive Röntgen-Nahkanten-Absorptions-Spektroskopie für die Untersuchung intermolekularer Wechselwirkungen und zeitabhängiger Prozesse während der Strukturbildung aufgezeigt. Als Modellsystem wurden hierbei 1,4,5,8- Naphthalin-Tetracarboxyls¨aure-Dianhydrid-(NTCDA-) Filme verwendet. Es wurde die Rumpfloch-Elektronen-Wechselwirkung kohärent gekoppelter Moleküle mittels energiedispersiver Röntgen-Nahkanten-Absorptions-Spektroskopie untersucht. Dabei wurde eine Übergangsphase gefunden, die während der Ausbildung einer langreichweitigen Ordnung zeitlich zwischen der ungeordneten und der Volumenstruktur auftritt. Diese Übergangsphase zeichnete sich durch eine charakteristische Änderung der spektralen Linienform und ihrer energetischen Position bei Messungen an der C K-Kante aus. Die experimentellen Befunde lassen sich mit Hilfe theoretischer Modelle erklären, welche die Kopplung von Übergangsdipolmomenten beschreiben. Diese theoretischen Konzepte sind bei optisch angeregten Systemen etabliert. Die experimentellen Ergebnisse zeigen den über mehrere Moleküle delokalisierten Charakter des Rumpfloch-Elektron-Paars. Zudem wurde die Strukturbildung von mehrlagigen NTCDA-Filmen auf Ag(111) untersucht. Zeitabhängige energiedispersive NEXAFS-Experimente mit s- und p-polarisiertem Licht zeigten ein charakteristisches Verhalten. In Kombination mit zeitabhängigen Photoemissionsmessungen wurden bei der Strukturbildung verschiedene Unterprozesse gefunden. Nach erwärmen der Probe richten sich die ursprünglich flach orientierte Moleküle zunächst auf. Im Anschluss folgt eine Aggregation der Moleküle in einer Phase mit starker intermolekularer Kopplung. Letztendlich bildet sich die bekannte dreidimensionale Filmstruktur aus. Anhand des Kolmogorov-Johnson-Mehl-Avrami Modells konnte die Aktivierungsenergie für die verschiedenen Unterprozesse ermittelt werden.
KW  - Organisches Molekül
KW  - NEXAFS
KW  - Zwischenmolekulare Kraft
KW  - Dünne Schicht
KW  - Energiedispersiv
KW  - Phasendynamik
KW  - Strukturbildung
KW  - NEXAFS
KW  - energy-dispersive
KW  - organic molecule
KW  - intermolecular interaction
KW  - phase dynamics
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-83839
ER  - 
TY  - JOUR
A1  - Scholz, Nicole
A1  - Guan, Chonglin
A1  - Nieberler, Matthias
A1  - Grotmeyer, Alexander
A1  - Maiellaro, Isabella
A1  - Gao, Shiqiang
A1  - Beck, Sebastian
A1  - Pawlak, Matthias
A1  - Sauer, Markus
A1  - Asan, Esther
A1  - Rothemund, Sven
A1  - Winkler, Jana
A1  - Prömel, Simone
A1  - Nagel, Georg
A1  - Langenhan, Tobias
A1  - Kittel, Robert J
T1  - Mechano-dependent signaling by Latrophilin/CIRL quenches cAMP in proprioceptive neurons
JF  - eLife
N2  - Adhesion-type G protein-coupled receptors (aGPCRs), a large molecule family with over 30 members in humans, operate in organ development, brain function and govern immunological responses. Correspondingly, this receptor family is linked to a multitude of diverse human diseases. aGPCRs have been suggested to possess mechanosensory properties, though their mechanism of action is fully unknown. Here we show that the Drosophila aGPCR Latrophilin/dCIRL acts in mechanosensory neurons by modulating ionotropic receptor currents, the initiating step of cellular mechanosensation. This process depends on the length of the extended ectodomain and the tethered agonist of the receptor, but not on its autoproteolysis, a characteristic biochemical feature of the aGPCR family. Intracellularly, dCIRL quenches cAMP levels upon mechanical activation thereby specifically increasing the mechanosensitivity of neurons. These results provide direct evidence that the aGPCR dCIRL acts as a molecular sensor and signal transducer that detects and converts mechanical stimuli into a metabotropic response.
KW  - Latrophilin
KW  - adhesion GPCR
KW  - dCIRL
KW  - sensory physiology
KW  - metabotropic signalling
KW  - mechanotransduction
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170520
VL  - 6
IS  - e28360
ER  -