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SDF-1/CXCR4 expression in head and neck cancer and outcome after postoperative radiochemotherapy
(2017)
Introduction: Outcome after postoperative radiochemotherapy (RT-CT) for patients with advanced head and neck squamous cell carcinomas (HNSCC) remains unsatisfactory, especially among those with HPV negative tumours. Therefore, new biomarkers are needed to further define subgroups for individualised therapeutic approaches. Preclinical and first clinical observations showed that the chemokine receptor CXCR4 and its ligand SDF-1 (CXCL12) play an important role in tumour cell proliferation, survival, cancer progression, metastasis and treatment resistance. However, the data on the prognostic value of SDF-1/CXCR4 expression for HNSCC are conflicting. The aim of our hypothesis-generating study was to retrospectively explore the prognostic potential of SDF-1/CXCR4 in a well-defined cohort of HNSCC patients collected within the multicenter biomarker study of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG).
Material and methods: Patients with stage III and IVA HNSCC of the oral cavity, oropharynx and hypopharynx were treated with resection and adjuvant radiotherapy (RT) with ≥60 Gy and concurrent cisplatin-based chemotherapy (CT). Tissue micro-arrays (TMAs) from a total of 221 patients were generated from surgical specimens, 201 evaluated for the SDF-1 and CXCR4 expression by immunofluorescence and correlated with clinico-pathological and outcome data.
Results: In univariate and multivariate analyses intracellular SDF-1 expression was associated with lower loco-regional control (LRC) in the entire patient group as well as in the HPV16 DNA negative subgroup. CXCR4 expression showed a trend for lower LRC in the univariate analysis which was not confirmed in the multivariate analysis. Neither for SDF-1 nor CXCR4 expression associations with distant metastasis free or overall survival were found.
Conclusions: Our exploratory data support the hypothesis that overexpression of intracellular SDF-1 is an independent negative prognostic biomarker for LRC after postoperative RT-CT in high-risk HNSCC. Prospective validation is warranted and further exploration of SDF-1/CXCR4 as a potential therapeutic target to overcome treatment resistance in HNSCC appears promising.
This work aims at radar sensors in the frequency band from 57 to 64 GHz that can be embedded in wind turbine blades during manufacturing, enabling non-destructive quality inspection directly after production and structural health monitoring (SHM) during the complete service life of the blade. In this paper, we show the fundamental damage detection capability of this sensor technology during fatigue testing of typical rotor blade materials. Therefore, a frequency modulated continuous wave (FMCW) radar sensor is used for damage diagnostics, and the results are validated by simultaneous camera recordings. Here, we focus on the failure modes delamination, fiber waviness (ondulation), and inter-fiber failure. For each failure mode, three samples have been designed and experimentally investigated during fatigue testing. A damage index has been proposed based on residual, that is, differential, signals exploiting measurements from pristine structural conditions. This study shows that the proposed innovative radar approach is able to detect continuous structural degradation for all failure modes by means of gradual signal changes.
Background. TLR ligands can promote Th1-biased immune responses, mimicking potent stimuli of viruses and bacteria. Aim. To investigate the adjuvant properties of dual TLR2/7 ligands compared to those of the mixture of both single ligands.
Methods. Dual TLR2/7 ligands: CL401, CL413, and CL531, including CL264 (TLR7-ligand) and Pam2CysK4 (TLR2-ligand), were used. Immune-modulatory capacity of the dual ligands with the individual ligands alone or as a mixture in mouse BMmDCs, BMmDC:TC cocultures, or BMCMCs was compared and assessed in naïve mice and in a mouse model of OVA-induced intestinal allergy.
Results. CL413 and CL531 induced BMmDC-derived IL-10 secretion, suppressed rOVA-induced IL-5 secretion from OVA-specific DO11.10 CD4+ TCs, and induced proinflammatory cytokine secretion in vivo. In contrast, CL401 induced considerably less IL-10 secretion and led to IL-17A production in BMmDC:TC cocultures, but not BMCMC IL-6 secretion, or IL-6 or TNF-α production in vivo. No immune-modulating effects were observed with single ligands. All dual TLR2/7 ligands suppressed DNP-induced IgE-and-Ag-specific mast cell degranulation. Compared to vaccination with OVA, vaccination with the mixture CL531 and OVA, significantly suppressed OVA-specific IgE production in the intestinal allergy model.
Conclusions. Based on beneficial immune-modulating properties, CL413 and CL531 may have utility as potential adjuvants for allergy treatment.
The objective of this study is to determine whether specific industries across countries or within countries are more likely to reach a stage of profitability and make a successful exit. In particular, we assess whether firms in certain industries are more prone to exit via IPO, be acquired, or exit through a leveraged buy-out. We are also interested in analyzing whether substantial differences across industries and countries arise when looking separately at the success’ rate of firms which have received venture funding at the early seed and start-up stages, vis-à-vis firms that received funding at later stages. Our results suggest that, inasmuch as some of the differences in performance can be explained by country-specific factors, there are also important idiosyncratic differences across industries: In particular, firms in the biotech and the medical / health / life science sectors tend to be significantly more likely to have a successful exit via IPO, while firms in the computer industry and communications and media are more prone to exit via merger or acquisition. Key differences across industries also emerge when considering infant versus mature firms, and their preferred exit. JEL Classification: G24, G3 Keywords:
Tumor cells frequently overexpress heat shock protein 70 (Hsp70) and present it on their cell surface, where it can be recognized by pre‐activated NK cells. In our retrospective study the expression of Hsp70 was determined in relation to tumor‐infiltrating CD56+ NK cells in formalin‐fixed paraffin embedded (FFPE) tumor specimens of patients with SCCHN (N = 145) as potential indicators for survival and disease recurrence. All patients received radical surgery and postoperative cisplatin‐based radiochemotherapy (RCT). In general, Hsp70 expression was stronger, but with variable intensities, in tumor compared to normal tissues. Patients with high Hsp70 expressing tumors (scores 3–4) showed significantly decreased overall survival (OS; p = 0.008), local progression‐free survival (LPFS; p = 0.034) and distant metastases‐free survival (DMFS; p = 0.044), compared to those with low Hsp70 expression (scores 0–2), which remained significant after adjustment for relevant prognostic variables. The adverse prognostic value of a high Hsp70 expression for OS was also observed in patient cohorts with p16‐ (p = 0.001), p53‐ (p = 0.0003) and HPV16 DNA‐negative (p = 0.001) tumors. The absence or low numbers of tumor‐infiltrating CD56+ NK cells also correlated with significantly decreased OS (p = 0.0001), LPFS (p = 0.0009) and DMFS (p = 0.0001). A high Hsp70 expression and low numbers of tumor‐infiltrating NK cells have the highest negative predictive value (p = 0.00004). In summary, a strong Hsp70 expression and low numbers of tumor‐infiltrating NK cells correlate with unfavorable outcome following surgery and RCT in patients with SCCHN, and thus serve as negative prognostic markers.
Im nordrhein-westfälischen Teil der Eifel (Nordeifel) ist das Luzulo-Fagetum Meusel 1937 aufgrund der geologischen und edaphischen Gegebenheiten die kennzeichnende Waldgesellschaft der Potentiellen natürlichen Vegetation. Die rezenten Bestände wurden anhand von 130 Aufnahmen nach Braun-Blanquet dokumentiert und differenziert. Demnach sind in diesem Teil der Eifel das Luzulo-Fagetum typicum und das auf reichere Wuchsorte beschränkte Luzulo-Fagetum milietosum anzutreffen. Innerhalb dieser Bestände wird auf sickerfeuchten Standorten eine Variante von Athyrium filix-femina, auf stau- bzw. wechselfeuchten hingegen eine Variante mit Deschampsia cespitosa erkennbar. Luvseitige Aushagerungsstandorte sind durch Avenella flexuosa, leeseitige Anreicherungsstandorte mit dicker Fallaub-Auflage durch Festuca altissima gekennzeichnet. Geographisch können die Bestände der nordmitteleuropäischen Ausbildung der subatlantischen Rasse des Luzulo-Fagetum zugeordnet werden.
Zur Verbreitung und Ökologie von Atriplex sagittata BORKH. (Glanz-Melde) im nördlichen Rheinland
(1994)
Atriplex sagittata BORKH. (Atriplex nitens Schkuhr) wurde schon vor 1850 gelegentlich ins Rheinland eingeschleppt, etablierte sich hier aber erst nach 1945 auf den Trümmern des kriegszerstörten Bonn in größerem Maße, um sich mit dem Wiederaufbau in Randgebiete zurückzuziehen. Heute tritt sie auf Müll-, Kehrricht- und Erdabkippflächen in z.T. ausgedehnten Dominanzbeständen auf, für welche die Bezeichnung Lactuco-Atriplicetum sagittatae als nomen novum vorgeschlagen wird. Im Rheinland kommt vor allem die Typische Subassoziation dieser Gesellschaft vor. In den oftmals deutlich geschichteten Beständen können nur wenige andere Stellarietea mediae-Arten nennenswerte Deckungsanteile erreichen. Für die Ausbreitung der Art und die Bildung ausgedehnter Herden ist vor allem die ausgeprägte Heterokarpie der Glanz-Melde verantwortlich. Daneben werden aber offensichtlich ganz spezifische Ansprüche an den Wuchsort gestellt. Die von uns untersuchten Substrate lassen sich als kalkhaltige, schwach alkalische, meist gut mit Phosphor und Kalium versorgte, schluffige Sande charakterisieren. Da Verwechslungen von Atriplex sagittata mit anderen hochwüchsigen Meldenarten nicht auszuschließen sind, werden in einem eigenen Kapitel wesentliche Unterscheidungsmerkmale vorgestellt.
Es werden genaue Angaben über Systematik, Morphologie, Verbreitung, Ökologie und Gefährdung von Dryopteris affinis (LOWE) FRASER-JENKINS in der Westeifel gemacht. Die Fundorte werden auf Übersichtskarten dargestellt und in einer ökologischen Tabelle und durch Vegetationsaufnahmen charakterisiert. Es zeigt sich, daß Dryopteris affinis im Untersuchungsgebiet vor allem auf Waldrand-Böschungen, aber auch in naturnahen Fagion-Gesellschaften wächst. Entscheidend für das Vorkommen der Art sind offensichtlich ausreichende Wasserversorgung, hohe Luftfeuchte sowie wintermildes Klima. Daher bevorzugt Dryopteris affinis auch in der Eifel die stärker atlantisch geprägten Gebiete. Dryopteris affinis lässt sich morphologisch relativ leicht von Dryopteris filix-mas unterscheiden. Nachweise von Dryopteris x complexa in der Westeifel fehlen bisher. Die Unterscheidung der Unterarten von Dryopteris affinis anhand rein morphologischer Merkmale gestaltet sich schwierig, jedoch scheinen nur die triploiden Sippen ssp. borreri und ssp. robusta vorzukommen. Unter dem Gesichtspunkt der Erhaltung des genetischen Potentials der von anderen Unterarten schwer zu unterscheidenden diploiden Unterart müssen die Wuchsorte von Dryopteris affinis unbedingt erhalten werden.
After nearly two decades of US leadership during the 1980s and 1990s, are Europe’s venture capital (VC) markets in the 2000s finally catching up regarding the provision of financing and successful exits, or is the performance gap as wide as ever? Are we amid an overall VC performance slump with no encouraging news? We attempt to answer these questions by tracking over 40,000 VC-backed firms stemming from six industries in 13 European countries and the US between 1985 and 2009; determining the type of exit – if any – each particular firm’s investors choose for the venture.
Comprehensive analysis of tumour sub-volumes for radiomic risk modelling in locally advanced HNSCC
(2020)
Simple Summary: Radiomic risk models are usually based on imaging features, which are extracted from the entire gross tumour volume (GTV entire ). This approach does not explicitly consider the complex biological structure of the tumours. Therefore, in this retrospective study, we investigated the prognostic value of radiomic analyses based on different tumour sub-volumes using computed tomography imaging of patients with locally advanced head and neck squamous cell carcinoma who were treated with primary radio-chemotherapy. The GTV entire was cropped by different margins to define the rim and corresponding core sub-volumes of the tumour. Furthermore, the best performing tumour rim sub-volume was extended into surrounding tissue with different margins. As a result, the models based on the 5 mm tumour rim and on the 3 mm extended rim sub-volume showed an improved performance compared to models based on the corresponding tumour core. This indicates that the consideration of tumour sub-volumes may help to improve radiomic risk models.
Abstract: Imaging features for radiomic analyses are commonly calculated from the entire gross tumour volume (GTVentire). However, tumours are biologically complex and the consideration of different tumour regions in radiomic models may lead to an improved outcome prediction. Therefore, we investigated the prognostic value of radiomic analyses based on different tumour sub-volumes using computed tomography imaging of patients with locally advanced head and neck squamous cell carcinoma. The GTVentire was cropped by different margins to define the rim and the corresponding core sub-volumes of the tumour. Subsequently, the best performing tumour rim sub-volume was extended into surrounding tissue with different margins. Radiomic risk models were developed and validated using a retrospective cohort consisting of 291 patients in one of the six Partner Sites of the German Cancer Consortium Radiation Oncology Group treated between 2005 and 2013. The validation concordance index (C-index) averaged over all applied learning algorithms and feature selection methods using the GTVentire achieved a moderate prognostic performance for loco-regional tumour control (C-index: 0.61 ± 0.04 (mean ± std)). The models based on the 5 mm tumour rim and on the 3 mm extended rim sub-volume showed higher median performances (C-index: 0.65 ± 0.02 and 0.64 ± 0.05, respectively), while models based on the corresponding tumour core volumes performed less (C-index: 0.59 ± 0.01). The difference in C-index between the 5 mm tumour rim and the corresponding core volume showed a statistical trend (p = 0.10). After additional prospective validation, the consideration of tumour sub-volumes may be a promising way to improve prognostic radiomic risk models.