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https://www.readbyqxmd.com/read/28094261/beyond-the-margins-real-time-detection-of-cancer-using-targeted-fluorophores
#1
REVIEW
Ray R Zhang, Alexandra B Schroeder, Joseph J Grudzinski, Eben L Rosenthal, Jason M Warram, Anatoly N Pinchuk, Kevin W Eliceiri, John S Kuo, Jamey P Weichert
Over the past two decades, synergistic innovations in imaging technology have resulted in a revolution in which a range of biomedical applications are now benefiting from fluorescence imaging. Specifically, advances in fluorophore chemistry and imaging hardware, and the identification of targetable biomarkers have now positioned intraoperative fluorescence as a highly specific real-time detection modality for surgeons in oncology. In particular, the deeper tissue penetration and limited autofluorescence of near-infrared (NIR) fluorescence imaging improves the translational potential of this modality over visible-light fluorescence imaging...
January 17, 2017: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/28059098/somatostatin-receptor-expression-related-to-tp53-and-rb1-alterations-in-pancreatic-and-extrapancreatic-neuroendocrine-neoplasms-with-a-ki67-index-above-20
#2
Björn Konukiewitz, Anna Melissa Schlitter, Moritz Jesinghaus, Dominik Pfister, Katja Steiger, Angela Segler, Abbas Agaimy, Bence Sipos, Giuseppe Zamboni, Wilko Weichert, Irene Esposito, Nicole Pfarr, Günter Klöppel
Somatostatin receptor 2A expression is a feature of well-differentiated neuroendocrine neoplasms and is important for their diagnosis and therapy. Little is known about somatostatin receptor 2A expression in poorly differentiated neuroendocrine neoplasms in relation to TP53 and RB1 status and how these features may contribute to the separation of well from poorly differentiated neuroendocrine neoplasms with a proliferation index above 20%. This study investigates the expression of somatostatin receptors, p53 and Rb1, and TP53 alterations in pancreatic and extrapancreatic well and poorly differentiated neuroendocrine neoplasms (Ki67-index >20%)...
January 6, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28059096/colorectal-mixed-adenoneuroendocrine-carcinomas-and-neuroendocrine-carcinomas-are-genetically-closely-related-to-colorectal-adenocarcinomas
#3
Moritz Jesinghaus, Björn Konukiewitz, Gisela Keller, Matthias Kloor, Katja Steiger, Magdalena Reiche, Roland Penzel, Volker Endris, Ruza Arsenic, Gratiana Hermann, Albrecht Stenzinger, Wilko Weichert, Nicole Pfarr, Günter Klöppel
Colorectal mixed adenoneuroendocrine carcinomas are rare and clinically aggressive neoplasms with considerable morphological heterogeneity. Data on their genomic characteristics and molecular associations to either conventional colorectal adenocarcinomas or poorly differentiated neuroendocrine neoplasms is still scarce, hampering optimized patient treatment and care. Tissue from 19 colorectal mixed adenoneuroendocrine carcinomas and eight colorectal poorly differentiated neuroendocrine neoplasms (neuroendocrine carcinomas) was microdissected and subjected to next-generation sequencing using a colorectal adenocarcinoma-specific panel comprising 196 amplicons covering 32 genes linked to colorectal adenocarcinoma, and poorly differentiated neuroendocrine neoplasm tumorigenesis...
January 6, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28047779/we-h-207a-08-characterization-of-a-broad-spectrum-cancer-targeted-mri-contrast-agent
#4
C Brunnquell, R Zhang, A Pinchuk, J Weichert
PURPOSE: To characterize the relaxation properties and tumor targeting capabilities of a novel alkylphosphocholine (APC) analog MR contrast agent, Gd-DO3A-404. METHODS: Relaxivities were measured via T1 and T2 mapping of Gd-DO3A-404 with inversion recovery and spin echo pulse sequences, respectively. Uptake was characterized in flank xenograft models of non-small cell lung cancer (A549) and glioma (U87) and compared with uptake of Dotarem. Mice (N=3 per model per agent) were delivered 2...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28047116/su-g-tep3-08-pre-clinical-radionuclide-therapy-dosimetry-in-several-pediatric-cancer-xenografts
#5
I Marsh, M Otto, J Weichert, D Baiu, B Bednarz
PURPOSE: The focus of this work is to perform Monte Carlo-based dosimetry for several pediatric cancer xenografts in mice treated with a novel radiopharmaceutical (131) I-CLR1404. METHODS: Four mice for each tumor cell line were injected with 8-13 µCi/g of the (124) 124I-CLR1404. PET/CT images of each individual mouse were acquired at 5-6 time points over the span of 96-170 hours post-injection. Following acquisition, the images were co-registered, resampled, rescaled, corrected for partial volume effects (PVE), and masked...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28035577/c-met-in-chromophobe-renal-cell-carcinoma
#6
Franziska Erlmeier, Philipp Ivanyi, Arndt Hartmann, Michael Autenrieth, Max Wiedemann, Wilko Weichert, Sandra Steffens
c-Met plays a role as a prognostic marker in clear cell renal cell carcinoma. In addition, recently the tyrosine kinase inhibitor cabozantinib targeting c-Met was approved for the treatment of advanced renal cell carcinoma (RCC). In contrast to clear cell RCC, little is known about c-Met expression patterns in rarer RCC subtypes. The aim of this study was to evaluate the prevalence, distribution and prognostic impact of c-Met expression on chromophobe (ch)RCC. Patients who underwent renal surgery due to chRCC were retrospectively evaluated...
February 2017: Medical Oncology
https://www.readbyqxmd.com/read/28035323/the-role-of-pd-l1-expression-and%C3%A2-intratumoral-lymphocytes-in%C3%A2-response%C3%A2-to-perioperative-chemotherapy%C3%A2-for-urothelial-carcinoma
#7
F Erlmeier, A K Seitz, G Hatzichristodoulou, L Stecher, M Retz, J E Gschwend, W Weichert, H R Kübler, T Horn
Introduction: Immunological pathways are relevant for the effectiveness of conventional cytotoxic chemotherapy. Recently, checkpoint inhibition of the PD-1/PD-L1 axis has been shown to be therapeutically relevant in urothelial carcinoma. Objective: To monitor PD-L1 expression on tumor cells and intratumoral infiltration with CD8 positive lymphocytes during perioperative chemotherapy for urothelial cancer and to evaluate their use as potential predictive markers for chemotherapy. Patients and Methods: Sixty-four patients with muscle-invasive urothelial cancer were included in the analysis...
October 27, 2016: Bladder Cancer
https://www.readbyqxmd.com/read/28024689/alk-testing-in-non-small-cell-lung-cancer-nsclc-immunohistochemistry-ihc-and-or-fluorescence-in-situ-hybridisation-fish-statement-of-the-germany-society-for-pathology-dgp-and-the-working-group-thoracic-oncology-aio-of-the-german-cancer-society-e-v-stellungnahme
#8
M von Laffert, P Schirmacher, A Warth, W Weichert, R Büttner, R M Huber, J Wolf, F Griesinger, M Dietel, Ch Grohé
The EML4-ALK pathway plays an important role in a significant subset of non-small cell lung cancer patients. Treatment options such as ALK tyrosine kinase inhibitors lead to improved progression free survival and overall survival. These therapeutic options are chosen on the basis of the identification of the underlying genetic signature of the EML-ALK translocation. Efficient and easily accessible testing tools are required to identify eligible patients in a timely fashion. While FISH techniques are commonly used to detect this translocation, the broad implementation of this type of ALK testing into routine diagnostics is not optimal due to technical, structural and financial reasons...
January 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28006830/-c-met-oncogene-in-renal-cell-carcinomas
#9
F Erlmeier, W Weichert, M Autenrieth, P Ivanyi, A Hartmann, S Steffens
c-Met plays a significant role in multiple cellular processes. Being encoded by a proto-oncogene, tyrosine kinase supports aggressive tumour behaviour such as tumour invasiveness and formation of metastases. For some subtypes of renal cell carcinoma studies have shown a association between c-Met expression and clinical outcome or prognosis. Therefore, c-Met represents a prognostic marker in renal cell carcinoma.Furthermore, c-MET will play a decisive role as a possible target for targeted therapies in the era of personalised medicine...
December 2016: Aktuelle Urologie
https://www.readbyqxmd.com/read/27980050/in-vivo-pet-imaging-of-the-cancer-integrin-%C3%AE-v%C3%AE-6-using-gallium-68-labelled-cyclic-rgd-nonapeptides
#10
Johannes Notni, Dominik Reich, Oleg V Maltsev, Tobias G Kapp, Katja Steiger, Frauke Hoffmann, Irene Esposito, Wilko Weichert, Horst Kessler, Hans-Jürgen Wester
: Expression of the cellular transmembrane receptor αvβ6 integrin is essentially restricted to malignant epithelial cells in carcinomas of a broad variety of lineages, while it is virtually absent in normal adult tissues. Thus, it is a highly attractive target for tumor imaging and therapy. Furthermore, αvβ6 integrin plays an important role for the epithelial-mesenchymal interaction and the development of fibrosis. METHODS: On the basis of the Gallium-68 chelators TRAP (triazacyclononane-triphosphinate) and NODAGA, we synthesized mono- di- and trimeric conjugates of the αvβ6 integrinselective peptide cyclo(FRGDLAFp(NMe)K) via click chemistry (CuAAC)...
December 15, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/27966437/physician-consensus-on-preventability-and-predictability-of-readmissions-based-on-standard-case-scenarios
#11
L S van Galen, T Cooksley, H Merten, M Brabrand, C B Terwee, C H Nickel, C P Subbe, R Kidney, J Soong, L Vaughan, I Weichert, M H H Kramer, P W B Nanayakkara
BACKGROUND: Policy makers struggle with unplanned readmissions as a quality indicator since integrating preventability in such indicators is difficult. Most studies on the preventability of readmissions questioned physicians whether they consider a given readmission to be preventable, from which conclusions on factors predicting preventable readmissions were derived. There is no literature on the interobserver agreement of physician judgement. AIM: To assess the degree of agreement among physicians regarding predictability and preventability of medical readmissions...
December 2016: Netherlands Journal of Medicine
https://www.readbyqxmd.com/read/27939606/typing-of-colon-and-lung-adenocarcinoma-by-high-throughput-imaging-mass-spectrometry
#12
Mark Kriegsmann, Rémi Longuespée, Petra Wandernoth, Cristina Mohanu, Katharina Lisenko, Wilko Weichert, Arne Warth, Hendrik Dienemann, Edwin De Pauw, Tiemo Katzenberger, Daniela Aust, Gustavo Baretton, Joerg Kriegsmann, Rita Casadonte
In advanced tumor stages, diagnosis is frequently made from metastatic tumor tissue. In some cases, the identification of the tumor of origin may be difficult by histology alone. In this setting, immunohistochemical and molecular biological methods are often required. In a subset of tumors definite diagnosis cannot be achieved. Thus, additional new diagnostic methods are required for precise tumor subtyping. Mass spectrometric methods are of special interest for the discrimination of different tumor types. We investigated whether it is possible to discern adenocarcinomas of colon and lung using high-throughput imaging mass spectrometry on formalin-fixed paraffin-embedded tissue microarrays...
December 8, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27935045/patient-derived-xenografts-of-gastrointestinal-cancers-are-susceptible-to-rapid-and-delayed-b-lymphoproliferation
#13
Sebastian M Dieter, Klara M Giessler, Mark Kriegsmann, Taronish D Dubash, Lino Möhrmann, Erik R Schulz, Christine Siegl, Sarah Weber, Hendrik Strakerjahn, Ava Oberlack, Ulrike Heger, Jianpeng Gao, Eva-Maria Hartinger, Felix Oppel, Christopher M Hoffmann, Nati Ha, Benedikt Brors, Felix Lasitschka, Alexis Ulrich, Oliver Strobel, Manfred Schmidt, Christof von Kalle, Martin Schneider, Wilko Weichert, K Roland Ehrenberg, Hanno Glimm, Claudia R Ball
Patient-derived cancer xenografts (PDX) are widely used to identify and evaluate novel therapeutic targets, and to test therapeutic approaches in preclinical mouse avatar trials. Despite their widespread use, potential caveats of PDX models remain considerably underappreciated. Here, we demonstrate that EBV-associated B-lymphoproliferations frequently develop following xenotransplantation of human colorectal and pancreatic carcinomas in highly immunodeficient NOD.Cg-Prkdc(scid) Il2rg(tm1Wjl) /SzJ (NSG) mice (18/47 and 4/37 mice, respectively), and in derived cell cultures in vitro...
December 9, 2016: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27933834/alginate-bead-based-hexagonal-close-packed-3d-implant-for-bone-tissue-engineering
#14
Tarun Agarwal, Prajna Kabiraj, Gautham Hari Narayana, Senthilguru Kulanthaivel, Uvanesh Kasiviswanathan, Kunal Pal, Supratim Giri, Tapas K Maiti, Indranil Banerjee
Success of bone tissue engineering (BTE) relies on the osteogenic microarchitecture of the biopolymeric scaffold and appropriate spatiotemporal distribution of therapeutic molecules (growth factors and drugs) inside it. However, the existing technologies have failed to address both the issues together. Keeping this perspective in mind, we have developed a novel three-dimensional (3D) implant prototype by stacking hexagonal close packed (HCP) layers of calcium alginate beads. The HCP arrangement of the beads lead to a patterned array of interconnected tetrahedral and octahedral pores of average diameter of 142...
November 30, 2016: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/27933395/influence-of-the-her-receptor-ligand-system-on-sensitivity-to-cetuximab-and-trastuzumab-in-gastric-cancer-cell-lines
#15
Julia Kneissl, Anja Hartmann, Nicole Pfarr, Franziska Erlmeier, Thomas Lorber, Simone Keller, Gwen Zwingenberger, Wilko Weichert, Birgit Luber
PURPOSE: Gastric cancer remains a major health concern, and improvement of the therapeutic options is crucial. Treatment with targeted therapeutics such as the EGFR-targeting antibody cetuximab or the HER2-targeting antibody trastuzumab is either ineffective or moderately effective in this disease, respectively. In this study, we analysed the involvement of the HER receptor ligands amphiregulin (AREG), epidermal growth factor (EGF), heparin-binding epidermal growth factor (HB-EGF) and transforming growth factor alpha (TGFα) in the responsiveness of gastric cancer cell lines to cetuximab and trastuzumab...
December 8, 2016: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/27923766/single-cell-analysis-uncovers-clonal-acinar-cell-heterogeneity-in-the-adult-pancreas
#16
Damian Wollny, Sheng Zhao, Isabelle Everlien, Xiaokang Lun, Jan Brunken, Daniel Brüne, Frederik Ziebell, Inna Tabansky, Wilko Weichert, Anna Marciniak-Czochra, Ana Martin-Villalba
Acinar cells make up the majority of all cells in the pancreas, yet the source of new acinar cells during homeostasis remains unknown. Using multicolor lineage-tracing and organoid-formation assays, we identified the presence of a progenitor-like acinar cell subpopulation. These cells have long-term self-renewal capacity, albeit in a unipotent fashion. We further demonstrate that binuclear acinar cells are terminally differentiated acinar cells. Transcriptome analysis of single acinar cells revealed the existence of a minor population of cells expressing progenitor markers...
November 7, 2016: Developmental Cell
https://www.readbyqxmd.com/read/27906217/nonlinearity-of-a-double-path-interferometer-qualified-with-a-non-constant-moving-speed
#17
Hongxing Yang, Christoph Weichert, Paul Köchert, Jens Flügge
A new double-path heterodyne interferometer with spatially separated input beams was developed to minimize the influence of periodic errors. The fully fiber-coupled optics exhibit balanced beam paths which reduce the influence of variations of the ambient conditions. The use of corner cube reflectors enables the interferometer to tolerate larger angular motions of the measuring mirror, compared with common plane mirror interferometers. The nonlinearities were characterized in a measurement with a non-constant moving speed by means of amplitude spectra for spline-interpolated data...
December 1, 2016: Optics Letters
https://www.readbyqxmd.com/read/27900363/integration-of-genomics-and-histology-revises-diagnosis-and-enables-effective-therapy-of-refractory-cancer-of-unknown-primary-with-pdl1-amplification
#18
Stefan Gröschel, Martin Bommer, Barbara Hutter, Jan Budczies, David Bonekamp, Christoph Heining, Peter Horak, Martina Fröhlich, Sebastian Uhrig, Daniel Hübschmann, Christina Geörg, Daniela Richter, Nicole Pfarr, Katrin Pfütze, Stephan Wolf, Peter Schirmacher, Dirk Jäger, Christof von Kalle, Benedikt Brors, Hanno Glimm, Wilko Weichert, Albrecht Stenzinger, Stefan Fröhling
Identification of the tissue of origin in cancer of unknown primary (CUP) poses a diagnostic challenge and is critical for directing site-specific therapy. Currently, clinical decision-making in patients with CUP primarily relies on histopathology and clinical features. Comprehensive molecular profiling has the potential to contribute to diagnostic categorization and, most importantly, guide CUP therapy through identification of actionable lesions. We here report the case of an advanced-stage malignancy initially mimicking poorly differentiated soft-tissue sarcoma that did not respond to multiagent chemotherapy...
November 2016: Cold Spring Harbor Molecular Case Studies
https://www.readbyqxmd.com/read/27869826/pan-cancer-analysis-of-somatic-copy-number-alterations-implicates-irs4-and-igf2-in-enhancer-hijacking
#19
Joachim Weischenfeldt, Taronish Dubash, Alexandros P Drainas, Balca R Mardin, Yuanyuan Chen, Adrian M Stütz, Sebastian M Waszak, Graziella Bosco, Ann Rita Halvorsen, Benjamin Raeder, Theocharis Efthymiopoulos, Serap Erkek, Christine Siegl, Hermann Brenner, Odd Terje Brustugun, Sebastian M Dieter, Paul A Northcott, Iver Petersen, Stefan M Pfister, Martin Schneider, Steinar K Solberg, Erik Thunissen, Wilko Weichert, Thomas Zichner, Roman Thomas, Martin Peifer, Aslaug Helland, Claudia R Ball, Martin Jechlinger, Rocio Sotillo, Hanno Glimm, Jan O Korbel
Extensive prior research focused on somatic copy-number alterations (SCNAs) affecting cancer genes, yet the extent to which recurrent SCNAs exert their influence through rearrangement of cis-regulatory elements (CREs) remains unclear. Here we present a framework for inferring cancer-related gene overexpression resulting from CRE reorganization (e.g., enhancer hijacking) by integrating SCNAs, gene expression data and information on topologically associating domains (TADs). Analysis of 7,416 cancer genomes uncovered several pan-cancer candidate genes, including IRS4, SMARCA1 and TERT...
January 2017: Nature Genetics
https://www.readbyqxmd.com/read/27836618/a-new-classification-method-for-maldi-imaging-mass-spectrometry-data-acquired-on-formalin-fixed-paraffin-embedded-tissue-samples
#20
Tobias Boskamp, Delf Lachmund, Janina Oetjen, Yovany Cordero Hernandez, Dennis Trede, Peter Maass, Rita Casadonte, Jörg Kriegsmann, Arne Warth, Hendrik Dienemann, Wilko Weichert, Mark Kriegsmann
Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) shows a high potential for applications in histopathological diagnosis, and in particular for supporting tumor typing and subtyping. The development of such applications requires the extraction of spectral fingerprints that are relevant for the given tissue and the identification of biomarkers associated with these spectral patterns. We propose a novel data analysis method based on the extraction of characteristic spectral patterns (CSPs) that allow automated generation of classification models for spectral data...
November 9, 2016: Biochimica et Biophysica Acta
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