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https://www.readbyqxmd.com/read/28324923/topotecan-vincristine-doxorubicin-in-stage-4-high-risk-neuroblastoma-patients-failing-to-achieve-a-complete-metastatic-response-to-rapid-cojec-a-siopen-study
#1
Loredana Amoroso, Giovanni Erminio, Guy Makin, Andrew Dj Pearson, Penelope Brock, Dominique Valteau-Couanet, Victoria Castel, Marlène Pasquet, Genevieve Laureys, Caroline Thomas, Roberto Luksch, Ruth Ladenstein, Riccardo Haupt, Alberto Garaventa
Purpose: Metastatic response to induction therapy for high-risk neuroblastoma is a prognostic factor. In the International Society of Paediatric Oncology Europe Neuroblastoma (SIOPEN) HR-NBL-1 protocol, only patients with metastatic complete response (CR) or partial response (PR) with ≤3 abnormal skeletal areas on 123iodine-metaiodobenzylguanidine ([123I]mIBG) scintigraphy and no bone marrow disease proceed to high dose therapy (HDT). In this study, topotecan-vincristine-doxorubicin (TVD) was evaluated in patients failing to achieve these criteria, with the aim of improving the metastatic response rate...
March 21, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/28304362/bdnf-variants-may-modulate-long-term-visual-memory-performance-in-a-healthy-cohort
#2
Nesli Avgan, Heidi G Sutherland, Lauren K Spriggens, Chieh Yu, Omar Ibrahim, Claire Bellis, Larisa M Haupt, David H K Shum, Lyn R Griffiths
Brain-derived neurotrophic factor (BDNF) is involved in numerous cognitive functions including learning and memory. BDNF plays an important role in synaptic plasticity in humans and rats with BDNF shown to be essential for the formation of long-term memories. We previously identified a significant association between the BDNF Val66Met polymorphism (rs6265) and long-term visual memory (p-value = 0.003) in a small cohort (n = 181) comprised of healthy individuals who had been phenotyped for various aspects of memory function...
March 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28301702/space-for-the-prisoner-s-point-of-view
#3
Laura Haupt
The lead article in this issue discusses a potentially free metaphorical space-that of decision-making-within the confines, tangible and intangible, of life in jail or prison. By interviewing prisoner-participants from six clinical studies, Paul Christopher and colleagues sought to find out how these men and women would answer open-ended questions about their decision to enroll in the research. What the interviewers heard was that none saw themselves as having been inappropriately pressured to do so. In fact, a significant percentage of the prisoners described being dissuaded from participating in the studies...
March 2017: Hastings Center Report
https://www.readbyqxmd.com/read/28300146/a-rapid-screening-approach-to-detect-and-quantify-microplastics-based-on-fluorescent-tagging-with-nile-red
#4
Thomas Maes, Rebecca Jessop, Nikolaus Wellner, Karsten Haupt, Andrew G Mayes
A new approach is presented for analysis of microplastics in environmental samples, based on selective fluorescent staining using Nile Red (NR), followed by density-based extraction and filtration. The dye adsorbs onto plastic surfaces and renders them fluorescent when irradiated with blue light. Fluorescence emission is detected using simple photography through an orange filter. Image-analysis allows fluorescent particles to be identified and counted. Magnified images can be recorded and tiled to cover the whole filter area, allowing particles down to a few micrometres to be detected...
March 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28265811/expert-system-for-bone-scan-interpretation-improves-progression-assessment-in-bone-metastatic-prostate-cancer
#5
Fabian Haupt, Georg Berding, Ali Namazian, Florian Wilke, Alena Böker, Axel Merseburger, Lilli Geworski, Markus Antonius Kuczyk, Frank Michael Bengel, Inga Peters
INTRODUCTION: The bone scan index (BSI) was introduced as a quantitative tool for tumor involvement in bone of patients with metastatic prostate cancer (mPCa). The computer-aided diagnosis device for BSI analysis EXINIbone(BSI) seems to represent technical progress for the quantitative assessment of bone involvement. But it is not yet clear if the automated BSI (aBSI) could contribute to improved evaluation of progression in patients under antiandrogens or chemotherapy in contrast to the visual interpretation and/or conventional biomarkers such as the prostate-specific antigen (PSA)...
March 7, 2017: Advances in Therapy
https://www.readbyqxmd.com/read/28255896/cell-and-tissue-imaging-with-molecularly-imprinted-polymers
#6
Maria Panagiotopoulou, Stephanie Kunath, Karsten Haupt, Bernadette Tse Sum Bui
Advanced tools for cell imaging are of particular interest as they can detect, localize and quantify molecular targets like abnormal glycosylation sites that are biomarkers of cancer and infection. Targeting these biomarkers is often challenging due to a lack of receptor materials. Molecularly imprinted polymers (MIPs) are promising artificial receptors; they can be tailored to bind targets specifically, be labeled easily, and are physically and chemically stable. Herein, we demonstrate the application of MIPs as artificial antibodies for selective labeling and imaging of cellular targets, on the example of hyaluronan and sialylation moieties on fixated human skin cells and tissues...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28255110/methylome-wide-association-study-of-whole-blood-dna-in-the-norfolk-island-isolate-identifies-robust-loci-associated-with-age
#7
Miles C Benton, Heidi G Sutherland, Donia Macartney-Coxson, Larisa M Haupt, Rodney A Lea, Lyn R Griffiths
Epigenetic regulation of various genomic functions, including gene expression, provide mechanisms whereby an organism can dynamically respond to changes in its environment and modify gene expression accordingly. One epigenetic mechanism implicated in human aging and age-related disorders is DNA methylation. Isolated populations such as Norfolk Island (NI) should be advantageous for the identification of epigenetic factors related to aging due to reduced genetic and environmental variation. Here we conducted a methylome-wide association study of age using whole blood DNA in 24 healthy female individuals from the NI genetic isolate (aged 24-47 years)...
February 28, 2017: Aging
https://www.readbyqxmd.com/read/28246187/tgf-%C3%AE-family-signaling-in-connective-tissue-and-skeletal-diseases
#8
Elena Gallo MacFarlane, Julia Haupt, Harry C Dietz, Eileen M Shore
The transforming growth factor β (TGF-β) family of signaling molecules, which includes TGF-βs, activins, inhibins, and numerous bone morphogenetic proteins (BMPs) and growth and differentiation factors (GDFs), has important functions in all cells and tissues, including soft connective tissues and the skeleton. Specific TGF-β family members play different roles in these tissues, and their activities are often balanced with those of other TGF-β family members and by interactions with other signaling pathways...
February 28, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28213222/development-of-a-qcm-d-biosensor-for-ochratoxin-a-detection-in-red-wine
#9
Aleksandra Karczmarczyk, Karsten Haupt, Karl-Heinz Feller
Ochratoxin A (OTA), a highly toxic compound, is one of the most widely spread mycotoxins that contaminates a large variety of agricultural commodities. Due to its presence in the food chain, it imposes a hazard on both human and animal health. Therefore, there is a need for precise, fast and simple methods for toxin quantification. Herein, a novel sensor based on a quartz crystal microbalance with dissipation monitoring (QCM-D) and antibodies for specific analyte recognition was developed for rapid and sensitive detection of OTA in red wine...
May 1, 2017: Talanta
https://www.readbyqxmd.com/read/28194847/enzyme-initiated-free-radical-polymerization-of-molecularly-imprinted-polymer-nanogels-on-a-solid-phase-with-an-immobilized-radical-source
#10
Mira Daoud Attieh, Yi Zhao, Assem Elkak, Aude Falcimaigne-Cordin, Karsten Haupt
An enzyme-mediated synthetic approach is described for the preparation of molecularly imprinted polymer nanoparticles (MIP-NPs) in aqueous media. Horseradish peroxidase (HRP) was used to initiate the polymerization of methacrylate or vinyl monomers and cross-linkers by catalyzing the generation of free radicals. To prevent entrapment of the enzyme in the cross-linked polymer, and to enable it to be reused, HRP was immobilized on a solid support. MIPs based on 4-vinylpyridine and 1,4-bis(acryloyl)piperazine for the recognition of 2,4-dichlorophenoxyacetic acid (2,4-D) and salicylic acid were synthesized in an aqueous medium...
March 13, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28134748/influence-of-common-polymorphisms-in-the-slc5a2-gene-on-metabolic-traits-in-subjects-at-increased-risk-of-diabetes-and-on-response-to-empagliflozin-treatment-in-patients-with-diabetes
#11
Heike Zimdahl, Axel Haupt, Michael Brendel, Louis Bour, Fausto Machicao, Afshin Salsali, Uli C Broedl, Hans-Juergen Woerle, Hans-Ulrich Häring, Harald Staiger
OBJECTIVE: Inhibition of the renal sodium-glucose cotransporter 2 (SGLT2) is a novel concept in the therapy of diabetes mellitus. In this study, we first assessed whether common single nucleotide polymorphisms (SNPs) in the SGLT2-encoding gene SLC5A2 affect diabetes-related metabolic traits in subjects at risk for type 2 diabetes and, second, whether these have pharmacogenetic relevance by interfering with the response to empagliflozin treatment in patients with type 2 diabetes. PATIENTS AND METHODS: Samples from a metabolically well-phenotyped cross-sectional study population (total N=2600) at increased risk for type 2 diabetes and pooled pharmacogenetic samples from patients from four phase III trials of empagliflozin (in total: 603 receiving empagliflozin, 305 receiving placebo) were genotyped for five common SNPs (minor allele frequencies ≥5%) present in the SLC5A2 gene locus...
April 2017: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/28097652/mdm4-is-a-rational-target-for-treating-breast-cancers-with-mutant-p53
#12
Panimaya Jeffreena Miranda, Daniel Buckley, Dinesh Raghu, Jia-Min B Pang, Elena A Takano, Reshma Vijayakumaran, Amina Fas Teunisse, Atara Posner, Tahlia Procter, Marco J Herold, Cristina Gamell, Jean-Christophe Marine, Stephen B Fox, Aart Jochemsen, Sue Haupt, Ygal Haupt
Mutation of the key tumour suppressor p53 defines a transition in the progression towards aggressive and metastatic breast cancer (BC) with the poorest outcome. Specifically, the p53 mutation frequency exceeds 50% in triple-negative BC. Key regulators of mutant p53 that facilitate its oncogenic functions are potential therapeutic targets. We report here that the MDM4 protein is frequently abundant in the context of mutant p53 in basal-like BC samples. Importantly, we show that MDM4 plays a critical role in the proliferation of these BC cells...
January 18, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28096293/the-role-of-mdm2-and-mdm4-in-breast-cancer-development-and-prevention
#13
REVIEW
Sue Haupt, Reshma Vijayakumaran, Jeffreena Panimaya, Andrew Burgess, Elgene Lim, Ygal Haupt
The major cause of death from breast cancer is not the primary tumour, but relapsing, drug-resistant, metastatic disease. Identifying factors that contribute to aggressive cancer offers important leads for therapy. Inherent defense against carcinogens depends on the individual molecular make-up of each person. Important molecular determinants of these responses are under the control of the mouse double minute (MDM) family: comprised of the proteins MDM2 and MDM4. In normal, healthy adult cells, the MDM family functions to critically regulate measured, cellular responses to stress and subsequent recovery...
January 17, 2017: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/28089731/investigation-of-polymorphisms-in-genes-involved-in-estrogen-metabolism-in-menstrual-migraine
#14
Heidi G Sutherland, Morgane Champion, Amelie Plays, Shani Stuart, Larisa M Haupt, Alison Frith, E Anne MacGregor, Lyn R Griffiths
Migraine is a common, disabling headache disorder, which is influenced by multiple genes and environmental triggers. After puberty, the prevalence of migraine in women is three times higher than in men and >50% of females suffering from migraine report a menstrual association, suggesting hormonal fluctuations can influence the risk of migraine attacks. It has been hypothesized that the drop in estrogen during menses is an important trigger for menstrual migraine. Catechol-O-methyltransferase (COMT) and Cytochrome P450 (CYP) enzymes are involved in estrogen synthesis and metabolism...
April 5, 2017: Gene
https://www.readbyqxmd.com/read/28074012/reduced-abundance-of-the-e3-ubiquitin-ligase-e6ap-contributes-to-decreased-expression-of-the-ink4-arf-locus-in-non-small-cell-lung-cancer
#15
Cristina Gamell, Twishi Gulati, Yaara Levav-Cohen, Richard J Young, Hongdo Do, Pat Pilling, Elena Takano, Neil Watkins, Stephen B Fox, Prudence Russell, Doron Ginsberg, Brendon J Monahan, Gavin Wright, Alex Dobrovic, Sue Haupt, Ben Solomon, Ygal Haupt
The tumor suppressor p16(INK4a), one protein encoded by the INK4/ARF locus, is frequently absent in multiple cancers, including non-small cell lung cancer (NSCLC). Whereas increased methylation of the encoding gene (CDKN2A) accounts for its loss in a third of patients, no molecular explanation exists for the remainder. We unraveled an alternative mechanism for the silencing of the INK4/ARF locus involving the E3 ubiquitin ligase and transcriptional cofactor E6AP (also known as UBE3A). We found that the expression of three tumor suppressor genes encoded in the INK4/ARF locus (p15(INK4b), p16(INK4a), and p19(ARF)) was decreased in E6AP(-/-) mouse embryo fibroblasts...
January 10, 2017: Science Signaling
https://www.readbyqxmd.com/read/28072840/locomotor-activity-and-body-temperature-patterns-over-a-temperature-gradient-in-the-highveld-mole-rat-cryptomys-hottentotus-pretoriae
#16
Meghan Haupt, Nigel C Bennett, Maria K Oosthuizen
African mole-rats are strictly subterranean mammals that live in extensive burrow systems. High humidity levels in the burrows prevent mole-rats from thermoregulating using evaporative cooling. However, the relatively stable environment of the burrows promotes moderate temperatures and small daily temperature fluctuations. Mole-rats therefore display a relatively wide range of thermoregulation abilities. Some species cannot maintain their body temperatures at a constant level, whereas others employ behavioural thermoregulation...
2017: PloS One
https://www.readbyqxmd.com/read/28034677/thermal-preference-and-performance-in-a-sub-antarctic-caterpillar-a-test-of-the-coadaptation-hypothesis-and-its-alternatives
#17
Tanya M Haupt, Brent J Sinclair, Steven L Chown
Physiological ecologists have long assumed that thermoregulatory behaviour will evolve to optimise physiological performance. The coadaptation hypothesis predicts that an animal's preferred body temperature will correspond to the temperature at which its performance is optimal. Here we use a strong inference approach to examine the relationship between thermal preference and locomotor performance in the caterpillars of a wingless sub-Antarctic moth, Pringleophaga marioni Viette (Tineidae). The coadaptation hypothesis and its alternatives (suboptimal is optimal, thermodynamic effect, trait variation) are tested...
December 27, 2016: Journal of Insect Physiology
https://www.readbyqxmd.com/read/27999330/dysregulated-microrna-expression-profiles-and-potential-cellular-circulating-and-polymorphic-biomarkers-in-non-hodgkin-lymphoma
#18
REVIEW
Gabrielle Bradshaw, Heidi G Sutherland, Larisa M Haupt, Lyn R Griffiths
A large number of studies have focused on identifying molecular biomarkers, including microRNAs (miRNAs) to aid in the diagnosis and prognosis of the most common subtypes of non-Hodgkin lymphoma (NHL), Diffuse Large B-cell Lymphoma and Follicular Lymphoma. NHL is difficult to diagnose and treat with many cases becoming resistant to chemotherapy, hence the need to identify improved biomarkers to aid in both diagnosis and treatment modalities. This review summarises more recent research on the dysregulated miRNA expression profiles found in NHL, as well as the regulatory role and biomarker potential of cellular and circulating miRNAs found in tissue and serum, respectively...
December 17, 2016: Genes
https://www.readbyqxmd.com/read/27936766/discovery-of-mycobacterium-tuberculosis-inha-inhibitors-by-binding-sites-comparison-and-ligands-prediction
#19
Tanja Štular, Samo Lešnik, Kaja Rožman, Julia Schink, Mitja Zdouc, An Ghysels, Feng Liu, Courtney C Aldrich, V Joachim Haupt, Sebastian Salentin, Simone Daminelli, Michael Schroeder, Thierry Langer, Stanislav Gobec, Dušanka Janežič, Janez Konc
Drug discovery is usually focused on a single protein target; in this process, existing compounds that bind to related proteins are often ignored. We describe ProBiS plugin, extension of our earlier ProBiS-ligands approach, which for a given protein structure allows prediction of its binding sites and, for each binding site, the ligands from similar binding sites in the Protein Data Bank. We developed a new database of precalculated binding site comparisons of about 290000 proteins to allow fast prediction of binding sites in existing proteins...
December 22, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27902311/ubiquitin-ligase-e6ap-mediates-nonproteolytic-polyubiquitylation-of-%C3%AE-catenin-independent-of-the-e6-oncoprotein
#20
Yael Kuslansky, Sophia Sominsky, Anna Jackman, Cristina Gamell, Brendon J Monahan, Ygal Haupt, Rina Rosin-Arbesfeld, Levana Sherman
Recently, we showed that the ubiquitin ligase E6AP stabilizes β-catenin and activates its transcriptional activity. These activities were enhanced by the human papillomavirus (HPV) E6 protein. In the present study, we explored the function of E6AP, which increases β-catenin stabilization and transcriptional activation. Here, we report that E6AP interacts with β-catenin and mediates its nonproteolytic ubiquitylation, as evidenced in transiently transfected cell-based and in vitro reconstitution ubiquitylation assays...
December 2016: Journal of General Virology
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