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https://www.readbyqxmd.com/read/28913154/pet-ct-imaging-of-the-diapeutic-alkylphosphocholine-analog-124-i-clr1404-in-high-and-low-grade-brain-tumors
#1
Lance T Hall, Benjamin Titz, H Ian Robins, Bryan P Bednarz, Scott B Perlman, Jamey P Weichert, John S Kuo
CLR1404 is a cancer-selective alkyl phosphocholine (APC) analog that can be radiolabeled with (124)I for PET imaging, (131)I for targeted radiotherapy and/or SPECT imaging, or (125)I for targeted radiotherapy. Studies have demonstrated avid CLR1404 uptake and prolonged retention in a broad spectrum of preclinical tumor models. The purpose of this pilot trial was to demonstrate avidity of (124)I-CLR1404 in human brain tumors and develop a framework to evaluate this uptake for use in larger studies. 12 patients (8 men and 4 women; mean age of 43...
2017: American Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28867147/lmo1-synergizes-with-mycn-to-promote-neuroblastoma-initiation-and-metastasis
#2
Shizhen Zhu, Xiaoling Zhang, Nina Weichert-Leahey, Zhiwei Dong, Cheng Zhang, Gonzalo Lopez, Ting Tao, Shuning He, Andrew C Wood, Derek Oldridge, Choong Yong Ung, Janine H van Ree, Amish Khan, Brittany M Salazar, Edroaldo Lummertz da Rocha, Mark W Zimmerman, Feng Guo, Hong Cao, Xiaonan Hou, S John Weroha, Antonio R Perez-Atayde, Donna S Neuberg, Alexander Meves, Mark A McNiven, Jan M van Deursen, Hu Li, John M Maris, A Thomas Look
A genome-wide association study identified LMO1, which encodes an LIM-domain-only transcriptional cofactor, as a neuroblastoma susceptibility gene that functions as an oncogene in high-risk neuroblastoma. Here we show that dβh promoter-mediated expression of LMO1 in zebrafish synergizes with MYCN to increase the proliferation of hyperplastic sympathoadrenal precursor cells, leading to a reduced latency and increased penetrance of neuroblastomagenesis. The transgenic expression of LMO1 also promoted hematogenous dissemination and distant metastasis, which was linked to neuroblastoma cell invasion and migration, and elevated expression levels of genes affecting tumor cell-extracellular matrix interaction, including loxl3, itga2b, itga3, and itga5...
September 11, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28822226/perinatal-outcomes-after-previable-preterm-premature-rupture-of-membranes-before-24-weeks-of-gestation
#3
Verena Kiver, Vinzenz Boos, Anke Thomas, Wolfgang Henrich, Alexander Weichert
OBJECTIVE: A current descriptive assessment of perinatal outcomes in pregnancies complicated by previable preterm premature rupture of membranes (pPPROM) at <24 weeks of gestation, after expectant treatment. STUDY DESIGN: Maternal and short-term neonatal data were collected for patients with pPPROM. RESULTS: Seventy-three patients with 93 fetuses were hospitalized with pPPROM at 15-24 weeks' gestation. Among these patients, 27.4% (n=20) chose pregnancy termination, 27...
August 19, 2017: Journal of Perinatal Medicine
https://www.readbyqxmd.com/read/28802189/pt-but-not-pn-stage-of-the-8th-tnm-classification-significantly-improves-prognostication-in-pancreatic-ductal-adenocarcinoma
#4
Anna Melissa Schlitter, Moritz Jesinghaus, Carsten Jäger, Björn Konukiewitz, Alexander Muckenhuber, Ihsan Ekin Demir, Marcus Bahra, Carsten Denkert, Helmut Friess, Günter Kloeppel, Güralp O Ceyhan, Wilko Weichert
The UICC TNM (tumour-node-metastasis) staging system for pancreatic ductal adenocarcinoma (PDAC) has been a matter of debate over decades because survival prediction based on T stages was weak and unreliable. To improve staging, the recently published 8th TNM edition (2016) introduced a conceptually completely changed strictly size-based T staging system and a refined N stage for PDAC. To investigate the clinical value of the novel TNM classification, we compared the prognostic impact of pT and pN stage between the 7th and 8th edition in two well-characterised independent German PDAC cohorts from different decades, including a total number of 523 patients...
August 9, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28772184/assessing-the-ecotoxicity-of-potentially-neurotoxic-substances-evaluation-of-a-behavioural-parameter-in-the-embryogenesis-of-danio-rerio
#5
Fabian G Weichert, Carolin Floeter, Adriana S Meza Artmann, Ulrike Kammann
The pollution of the aquatic environment is currently characterised by a large number of contaminants, especially by mixtures of micro-pollutants including neurotoxins. The ecotoxicological consequences of this burden are not yet assessable. Within the present study, a new test method was applied which evaluates behavioural changes in zebrafish (Danio rerio) embryos to quantify the neurotoxic effect of selected chemicals. Changes in the frequency of spontaneous tail movements - a parameter of locomotion - occurring during embryogenesis was assessed as parameter for neurotoxic effects...
November 2017: Chemosphere
https://www.readbyqxmd.com/read/28771236/the-cubicon-method-for-concentrating-membrane-proteins-in-the-cubic-mesophase
#6
Pikyee Ma, Dietmar Weichert, Luba A Aleksandrov, Timothy J Jensen, John R Riordan, Xiangyu Liu, Brian K Kobilka, Martin Caffrey
The lipid cubic phase (in meso) method is an important approach for generating crystals and high-resolution X-ray structures of integral membrane proteins. However, as a consequence of instability, it can be impossible-using traditional methods-to concentrate certain membrane proteins and complexes to values suitable for in meso crystallization and structure determination. The cubicon method described here exploits the amphiphilic nature of membrane proteins and their natural tendency to partition preferentially into lipid bilayers from aqueous solution...
September 2017: Nature Protocols
https://www.readbyqxmd.com/read/28747518/targeted-molecular-radiotherapy-of-pediatric-solid-tumors-using-a-radioiodinated-alkyl-phospholipid-ether-analog
#7
Dana C Baiu, Ian R Marsh, Alexander E Boruch, Ankita Shahi, Saswati Bhattacharya, Justin J Jeffery, Qianqian Zhao, Lance Hall, Jamey P Weichert, Bryan Bednarz, Mario Otto
External beam radiotherapy plays a critical role in the treatment of most pediatric solid tumors. Particularly in children, achieving an optimal therapeutic index to avoid damage to normal tissue is extremely important. Consequently, in metastatic disease, the utility of external beam radiotherapy is very limited. Molecular radiotherapy with tumor-targeted radionuclides may overcome some of these challenges, but to date no single cancer selective agent exists, capable of treating various pediatric malignancies independent of their histopathological origin...
July 26, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28741114/-fetal-autopsies-relic-or-still-a%C3%A2-gold-standard
#8
J Andruszkow, W Weichert, T Braunschweig, R Knüchel-Clarke, F Erlmeier
BACKGROUND: Fetal autopsy rates are decreasing in Western countries although post-mortem examinations render important information for the parents concerning the cause of abortion and risk of recurrence in future pregnancies. OBJECTIVE: The intention of the presented study was to analyze the development of fetal autopsies in Germany during the last decade and to review accessible information obtained by fetal autopsy. MATERIAL AND METHODS: Reports of fetal autopsies conducted in two German university Institutes of pathology between 2005 and 2014 were evaluated retrospectively...
July 24, 2017: Der Pathologe
https://www.readbyqxmd.com/read/28698908/-adult-autopsies-during-the-past-decade-in-germany-data-from-two-university-hospitals
#9
F Erlmeier, W Weichert, R Knüchel, J Andruszkow
BACKGROUND: The clinical autopsy is the ultimate medical service for a patient and plays a crucial role in the education of physicians and other medical personnel, as well as in the context of quality control. Nevertheless, the number of autopsies is constantly decreasing. Numerous factors, such as the personal attitude of relatives and also clarification of relatives, as well as the increasing application of imaging methods while the patient is still alive, play a central role in this decline...
July 11, 2017: Der Pathologe
https://www.readbyqxmd.com/read/28692477/r0-versus-r1-resection-matters-after-pancreaticoduodenectomy-and-less-after-distal-or-total-pancreatectomy-for-pancreatic-cancer
#10
Ihsan Ekin Demir, Carsten Jäger, A Melissa Schlitter, Björn Konukiewitz, Lynne Stecher, Stephan Schorn, Elke Tieftrunk, Florian Scheufele, Lenika Calavrezos, Rebekka Schirren, Irene Esposito, Wilko Weichert, Helmut Friess, Güralp O Ceyhan
OBJECTIVE: The aim of this study was to decipher the true importance of R0 versus R1 resection for survival in pancreatic ductal adenocarcinoma (PDAC). SUMMARY OF BACKGROUND DATA: PDAC is characterized by poor survival, even after curative resection. In many studies, R0 versus R1 does not result in different prognosis and does not affect the postoperative management. METHODS: Pubmed, Embase, and Cochrane databases were screened for prognostic studies on the association between resection status and survival...
July 7, 2017: Annals of Surgery
https://www.readbyqxmd.com/read/28682793/impact-of-pet-and-mri-threshold-based-tumor-volume-segmentation-on-patient-specific-targeted-radionuclide-therapy-dosimetry-using-clr1404
#11
Abigail E Besemer, Benjamin Titz, Joseph J Grudzinski, Jamey P Weichert, John S Kuo, H Ian Robins, Lance T Hall, Bryan P Bednarz
Variations in tumor volume segmentation methods in targeted radionuclide therapy (TRT) may lead to dosimetric uncertainties. This work investigates the impact of PET and MRI threshold-based tumor segmentation on TRT dosimetry in patients with primary and metastatic brain tumors. In this study, PET/CT images of five brain cancer patients were acquired at 6, 24, and 48 h post-injection of (124)I-CLR1404. The tumor volume was segmented using two standardized uptake value (SUV) threshold levels, two tumor-to-background ratio (TBR) threshold levels, and a T1 Gadolinium-enhanced MRI threshold...
July 6, 2017: Physics in Medicine and Biology
https://www.readbyqxmd.com/read/28675161/structural-insights-into-the-mechanism-of-the-membrane-integral-n-acyltransferase-step-in-bacterial-lipoprotein-synthesis
#12
Maciej Wiktor, Dietmar Weichert, Nicole Howe, Chia-Ying Huang, Vincent Olieric, Coilín Boland, Jonathan Bailey, Lutz Vogeley, Phillip J Stansfeld, Nienke Buddelmeijer, Meitian Wang, Martin Caffrey
Lipoproteins serve essential roles in the bacterial cell envelope. The posttranslational modification pathway leading to lipoprotein synthesis involves three enzymes. All are potential targets for the development of new antibiotics. Here we report the crystal structure of the last enzyme in the pathway, apolipoprotein N-acyltransferase, Lnt, responsible for adding a third acyl chain to the lipoprotein's invariant diacylated N-terminal cysteine. Structures of Lnt from Pseudomonas aeruginosa and Escherichia coli have been solved; they are remarkably similar...
July 4, 2017: Nature Communications
https://www.readbyqxmd.com/read/28657901/increased-intraepithelial-cd3-t-lymphocytes-and-high-pd-l1-expression-on-tumor-cells-are-associated-with-a-favorable-prognosis-in-esophageal-squamous-cell-carcinoma-and-allow-prognostic-immunogenic-subgrouping
#13
Moritz Jesinghaus, Katja Steiger, Julia Slotta-Huspenina, Enken Drecoll, Nicole Pfarr, Petra Meyer, Björn Konukiewitz, Marcus Bettstetter, Kathrin Wieczorek, Katja Ott, Markus Feith, Rupert Langer, Wilko Weichert, Katja Specht, Melanie Boxberg
Esophageal squamous cell carcinoma (ESCC) is the most common esophageal cancer associated with poor prognosis and additional therapeutic strategies must be implemented to optimize ESCC treatment. Meanwhile, the important biologic role and potential prognostic and therapeutic implications of a tumors immunologic microenvironment (IM) have been recognized in various cancers.In order to investigate the contexture and the prognostic relevance of the IM in ESCC, we immunohistochemically evaluated the extent of overall/intraepithelial TILs (CD3+/CD8+) and of PD-1 / PD-L1 expression in a cohort of 125 therapy-naive ESCCs, additionally assessing PD-L1 copy number status via fluorescence in-situ hybridization...
July 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28648701/universal-genomic-testing-the-next-step-in-oncological-decision-making-or-a-dead-end-street
#14
Julian Walter Holch, Klaus Hans Metzeler, Andreas Jung, Kristina Riedmann, Philipp Jakob Jost, Wilko Weichert, Thomas Kirchner, Volker Heinemann, Christoph Benedikt Westphalen
The concept of 'personalised medicine' aims at allocating patients to different treatment options based on individual characteristics to optimise treatment benefit and side effects. In oncology, personalised treatments coupled to biomarkers have led to the approval of targeted agents with high anti-tumour activity. However, these therapies are often limited to narrow, molecularly defined subsets of patients with a specific morphomolecular tumour profile. Recently, it became obvious that the same molecular alteration might drive oncogenesis in many different tumours, and it might be beneficial to target the alteration in a histology informed but entity-overarching way...
September 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28642333/patients-and-providers-perceptions-of-the-preventability-of-hospital-readmission-a-prospective-observational-study-in-four-european-countries
#15
Louise S van Galen, Mikkel Brabrand, Tim Cooksley, Peter M van de Ven, Hanneke Merten, Ralph Kl So, Loes van Hooff, Harm R Haak, Rachel M Kidney, Christian H Nickel, John Ty Soong, Immo Weichert, Mark Hh Kramer, Christian P Subbe, Prabath Wb Nanayakkara
OBJECTIVES: Because of fundamental differences in healthcare systems, US readmission data cannot be extrapolated to the European setting: To investigate the opinions of readmitted patients, their carers, nurses and physicians on predictability and preventability of readmissions and using majority consensus to determine contributing factors that could potentially foresee (preventable) readmissions. DESIGN: Prospective observational study. Readmitted patients, their carers, and treating professionals were surveyed during readmission to assess the discharge process and the predictability and preventability of the readmission...
June 22, 2017: BMJ Quality & Safety
https://www.readbyqxmd.com/read/28639280/mutational-profiles-of-brenner-tumors-show-distinctive-features-uncoupling-urothelial-carcinomas-and-ovarian-carcinoma-with-transitional-cell-histology
#16
Nicole Pfarr, Silvia Darb-Esfahani, Jonas Leichsenring, Eliane Taube, Melanie Boxberg, Ioana Braicu, Moritz Jesinghaus, Roland Penzel, Volker Endris, Aurelia Noske, Wilko Weichert, Peter Schirmacher, Carsten Denkert, Albrecht Stenzinger
Brenner tumors (BT) are rare ovarian tumors encompassing benign, borderline, and malignant variants. While the histopathology of BTs and their clinical course is well described, little is known about the underlying genetic defects. We employed targeted next generation sequencing to analyze the mutational landscape in a cohort of 23 BT cases (17 benign, 2 borderline, and 4 malignant) and 3 ovarian carcinomas with transitional cell histology (TCC). Copy number variations (CNV) were validated by fluorescence in-situ hybridization (FISH) and quantitative PCR-based copy number assays...
October 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/28634753/fetal-cephaloceles-prenatal-diagnosis-and-course-of-pregnancy-in-65-consecutive-cases
#17
Jan Weichert, Friederike Hoellen, Martin Krapp, Ute Germer, Roland Axt-Fliedner, Andrea Kempe, Annegret Geipel, Christoph Berg, Ulrich Gembruch
PURPOSE: To scrutinize the characteristics of all cases with antenatally established diagnosis of cephalocele in two tertiary referral centers. METHODS: We retrospectively reviewed 65 cases diagnosed with cephaloceles and tabulated sonographic findings and autopsy recordings as well as medical charts of all survivors in terms of clinical outcome. RESULTS: The case notes of 65 fetuses were available for final analysis. Gestational age (GA) at diagnosis ranged from 10...
June 20, 2017: Archives of Gynecology and Obstetrics
https://www.readbyqxmd.com/read/28627323/perspective-of-%C3%AE-v%C3%AE-6-integrin-imaging-for-clinical-management-of-pancreatic-carcinoma-and-its-precursor-lesions
#18
Katja Steiger, Anna-Melissa Schlitter, Wilko Weichert, Irene Esposito, Hans-Jürgen Wester, Johannes Notni
ß6-integrin immunohistochemistry analysis of a large number of pancreatic ductal adenocarcinoma (PDAC, 383 primary tumors, 7 lymph node, and 8 distant metastases) and 34 pancreatic intraepithelial neoplasia (PanIN) specimens revealed a high prevalence of αvß6-integrin expression in PDAC primaries (88%) and in almost all metastases, as well as in PanIN (57%). These findings underscore the high potential of a novel αvß6-integrin targeting positron emission tomography (PET) radiopharmaceutical, Ga-68-Avebehexin, for early diagnosis of pancreatic cancer...
January 1, 2017: Molecular Imaging
https://www.readbyqxmd.com/read/28597939/precision-oncology-based-on-omics-data-the-nct-heidelberg-experience
#19
Peter Horak, Barbara Klink, Christoph Heining, Stefan Gröschel, Barbara Hutter, Martina Fröhlich, Sebastian Uhrig, Daniel Hübschmann, Matthias Schlesner, Roland Eils, Daniela Richter, Katrin Pfütze, Christina Geörg, Bettina Meißburger, Stephan Wolf, Angela Schulz, Roland Penzel, Esther Herpel, Martina Kirchner, Amelie Lier, Volker Endris, Stephan Singer, Peter Schirmacher, Wilko Weichert, Albrecht Stenzinger, Richard F Schlenk, Evelin Schröck, Benedikt Brors, Christof von Kalle, Hanno Glimm, Stefan Fröhling
Precision oncology implies the ability to predict which patients will likely respond to specific cancer therapies based on increasingly accurate, high-resolution molecular diagnostics as well as the functional and mechanistic understanding of individual tumors. While molecular stratification of patients can be achieved through different means, a promising approach is next-generation sequencing of tumor DNA and RNA, which can reveal genomic alterations that have immediate clinical implications. Furthermore, certain genetic alterations are shared across multiple histologic entities, raising the fundamental question of whether tumors should be treated by molecular profile and not tissue of origin...
September 1, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28579623/reference-curve-for-the-mean-uterine-artery-pulsatility-index-in-singleton-pregnancies
#20
Alexander Weichert, Andreas Hagen, Michael Tchirikov, Ilka B Fuchs, Wolfgang Henrich, Michael Entezami
INTRODUCTION: Doppler sonography of the uterine artery (UA) is done to monitor pregnancies, because the detected flow patterns are useful to draw inferences about possible disorders of trophoblast invasion. Increased resistance in the UA is associated with an increased risk of preeclampsia and/or intrauterine growth restriction (IUGR) and perinatal mortality. In the absence of standardized figures, the normal ranges of the various available reference curves sometimes differ quite substantially from one another...
May 2017: Geburtshilfe und Frauenheilkunde
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