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https://www.readbyqxmd.com/read/29778738/risk-adapted-therapy-for-young-children-with-medulloblastoma-sjyc07-therapeutic-and-molecular-outcomes-from-a-multicentre-phase-2-trial
#1
Giles W Robinson, Vasilisa A Rudneva, Ivo Buchhalter, Catherine A Billups, Sebastian M Waszak, Kyle S Smith, Daniel C Bowers, Anne Bendel, Paul G Fisher, Sonia Partap, John R Crawford, Tim Hassall, Daniel J Indelicato, Frederick Boop, Paul Klimo, Noah D Sabin, Zoltan Patay, Thomas E Merchant, Clinton F Stewart, Brent A Orr, Jan O Korbel, David T W Jones, Tanvi Sharma, Peter Lichter, Marcel Kool, Andrey Korshunov, Stefan M Pfister, Richard J Gilbertson, Robert P Sanders, Arzu Onar-Thomas, David W Ellison, Amar Gajjar, Paul A Northcott
BACKGROUND: Young children with medulloblastoma have a poor overall survival compared with older children, due to use of radiation-sparing therapy in young children. Radiotherapy is omitted or reduced in these young patients to spare them from debilitating long-term side-effects. We aimed to estimate event-free survival and define the molecular characteristics associated with progression-free survival in young patients with medulloblastoma using a risk-stratified treatment strategy designed to defer, reduce, or delay radiation exposure...
May 16, 2018: Lancet Oncology
https://www.readbyqxmd.com/read/29778346/energy-performance-evaluation-of-ultrasonic-pretreatment-of-organic-solid-waste-in-a-pilot-scale-digester
#2
Mazdak Rasapoor, Mehrdad Adl, Saeid Baroutian, Zeynab Iranshahi, Mohammad Pazouki
It has been proven that ultrasonic pretreatment (UP) has positive effect on biogas generation from previous lab-scale studies. However, that is not always the case in larger scale processes. The purpose of this study was to evaluate the effectiveness of UP to biogas generation in terms of anaerobic digestion process and energy efficiency. Parameters including total solids (TS) and ultrasonic treatment operational parameters of organic solid waste (OSW) resulted from our past lab scale UP studies were applied in this study...
April 30, 2018: Ultrasonics Sonochemistry
https://www.readbyqxmd.com/read/29777201/novel-smoothened-inhibitors-for-therapeutic-targeting-of-na%C3%A3-ve-and-drug-resistant-hedgehog-pathway-driven-cancers
#3
Qing-Rou Li, Hui Zhao, Xue-Sai Zhang, Henk Lang, Ker Yu
The G protein-coupled receptor (GPCR) smoothened (SMO) is a key signaling component of the sonic hedgehog (Hh) pathway and a clinically validated target for cancer treatment. The FDA-approved SMO inhibitors GDC-0449/Vismodegib and LDE225/Sonidegib demonstrated clinical antitumor efficacy. Nevertheless, relatively high percentage of treated patients would eventually develop acquired cross resistance to both drugs. Here, based on published structure and activity of GDC-0449 inhibitor class, we replaced its amide core with benzimidazole which retained bulk of the SMO-targeting activity as measured in our Hh/SMO/Gli1-reporter system...
May 18, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29776636/molecular-diagnostics-in-the-neoplasms-of-the-pancreas-liver-gallbladder-and-extrahepatic-biliary-tract-2018-update
#4
REVIEW
Lei Zhang, Martin H Bluth, Amarpreet Bhalla
Pancreatic neoplasms, including ductal adenocarcinoma, solid pseudopapillary neoplasm, pancreatic endocrine neoplasms, acinar cell carcinoma, and pancreatoblastoma, are associated with different genetic abnormalities. Hepatic adenomas with beta-catenin exon 3 mutation are associated with a high risk of malignancy. Hepatic adenoma with arginosuccinate synthetase 1 expression or sonic hedgehog mutations are associated with a risk of bleeding. Hepatocellular carcinoma and choangiocarcinoma display heterogeneity at both morphologic and molecular levels Cholangiocellular carcinoma is most commonly associated with IDH 1/2 mutations...
June 2018: Clinics in Laboratory Medicine
https://www.readbyqxmd.com/read/29776351/a-computational-study-of-hedgehog-signalling-involved-in-basal-cell-carcinoma-reveals-the-potential-and-limitation-of-combination-therapy
#5
Antoine Buetti-Dinh, Rebecca Jensen, Ran Friedman
BACKGROUND: The smoothened (SMO) receptor is an essential component of the Sonic hedgehog (SHH) signalling, which is associated with the development of skin basal cell carcinoma (BCC). SMO inhibitors are indicated for BCC patients when surgical treatment or radiation therapy are not possible. Unfortunately, SMO inhibitors are not always well tolerated due to severe side effects, and their therapeutical success is limited by resistance mutations. METHODS: We investigated how common are resistance-causing mutations in two genomic databases which are not linked to BCC or other cancers, namely 1000 Genomes and ExAC...
May 18, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29775835/analysis-of-the-cytotoxic-effects-of-combined-ultrasound-microbubble-and-nucleoside-analog-combinations-on-pancreatic-cells-in-vitro
#6
Julia Mariglia, Shadab Momin, Imogen R Coe, Raffi Karshafian
Ultrasonically-stimulated microbubbles enhance the therapeutic effects of various chemotherapy drugs. However, the application of ultrasound and microbubbles (USMB) for enhancing the therapeutic effect of nucleoside analogs, which are used as front-line treatments in a range of cancers, and its underlying mechanism is not well understood. This study investigated the effect of gemcitabine, a nucleoside analog drug, in combination with USMB in increasing cell cytotoxicity relative to either treatment alone in BxPC3 pancreatic cancer cells...
May 5, 2018: Ultrasonics
https://www.readbyqxmd.com/read/29774894/value-of-diffusion-weighted-imaging-for-monitoring-tissue-change-during-magnetic-resonance-guided-high-intensity-focused-ultrasound-therapy-in-bone-applications-an-ex-vivo-study
#7
Sharon L Giles, Jessica M Winfield, David J Collins, Ian Rivens, John Civale, Gail R Ter Haar, Nandita M deSouza
Background: Magnetic resonance (MR)-guided high-intensity focused ultrasound (HIFU) can palliate metastatic bone pain by periosteal neurolysis. We investigated the value of diffusion-weighted imaging (DWI) for monitoring soft tissue changes adjacent to bone during MR-guided HIFU. We evaluated the repeatability of the apparent diffusion coefficient (ADC) measurement, the temporal evolution of ADC change after sonication, and its relationship with thermal parameters. Methods: Ex-vivo experiments in lamb legs ( n = 8) were performed on a Sonalleve MR-guided HIFU system...
2018: European radiology experimental
https://www.readbyqxmd.com/read/29774328/solvent-dependent-pathway-complexity-and-seeded-supramolecular-polymerization
#8
Goutam Ghosh, Suhrit Ghosh
cNDI-1 exhibits an off-pathway aggregate in cyclic hydrocarbon (MCH) but produces a helical supramolecular polymer in linear alkane (decane) by well-defined J-aggregation. Effective solvent-assisted nucleation in linear alkanes due to shape matching with the peripheral alkyl chains of a monomer is responsible for the pathway complexity. Seed, produced by sonication induced fragmentation of the fibers in decane, could initiate supramolecular polymerization of the off-pathway aggregate in MCH generating controllable helical nanostructures...
May 18, 2018: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/29773652/stromal-gli-signaling-regulates-the-activity-and-differentiation-of-prostate-stem-and-progenitor-cells
#9
Qianjin Li, Omar A Alsaidan, Sumit Rai, Meng Wu, Huifeng Shen, Zanna Beharry, Luciana L Almada, Martin E Fernandez-Zapico, Lianchun Wang, Houjian Cai
Interactions between cells in the stroma and epithelium facilitate prostate stem cell activity and tissue regeneration capacity. Numerous molecular signal transduction pathways, including the induction of sonic hedgehog (Shh) to activate the Gli transcription factors, are known to mediate the crosstalk of these two cellular compartments. However, the details of how these signaling pathways regulate prostate stem and progenitor cell activity remain elusive. Here we demonstrate that while cell autonomous epithelial Shh-Gli signaling is essential to determine the expression levels of basal cell markers and the renewal potential of epithelial stem and progenitor cells, stromal Gli signaling regulates prostate stem and progenitor cell activity by increasing the number and size of prostate spheroids in vitro...
May 17, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29772335/effect-of-nanofibers-fraction-on-properties-of-the-starch-based-biocomposite-prepared-in-various-ultrasonic-power
#10
Hairul Abral, Arya Satya Anugrah, Fadli Hafizulhaq, Dian Handayani, Eni Sugiarti, Ahmad Nove Muslimin
This paper characterizes starch based biocomposite reinforced with varied nanofiber fractions, i.e. 35.4, 70.8 and 106.2 μg per 10 g of starch. During preparation, the biocomposite in form of gel was sonicated using an ultrasonic probe at various powers, i.e. 0, 480, 600, 720 watt at 20 kHz for 5 min. The results show that ultrasonication results in a significant improvement in biocomposite properties for each of the nanofiber fractions. The tensile strength, moisture resistance of the 35.4 μg nanofibers biocomposite increase significantly 279, 11% respectively after 600 watt ultrasonication...
May 14, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29772066/3d-specific-absorption-rate-estimation-from-high-intensity-focused-ultrasound-sonications-using-the-green-s-function-heat-kernel
#11
Nicholas J Freeman, Henrik Odéen, Dennis L Parker
PURPOSE: Evaluate a numerical inverse Green's function method of deriving specific absorption rates (SARs) from high intensity focused ultrasound (HIFU) sonications given tissue parameters (thermal conductivity, specific heat capacity, and mass density) and 3-D magnetic resonance imaging (MRI) temperature measurements. METHODS: SAR estimates were evaluated using simulations and MR temperature measurements from HIFU sonications. For simulations, a "true" SAR was calculated using the hybrid angular spectrum method for ultrasound simulations...
May 17, 2018: Medical Physics
https://www.readbyqxmd.com/read/29771309/identification-of-a-specific-domain-of-porphyromonas-gingivalis-hgp44-responsible-for-adhesion-to-treponema-denticola
#12
Kouki Yoshikawa, Yuichiro Kikuchi, Eitoyo Kokubu, Kentaro Imamura, Atsushi Saito, Kazuyuki Ishihara
Interaction between two periodontal pathogens, Porphyromonas gingivalis and Treponema denticola, contributes to plaque biofilm formation. P. gingivalis forms aggregates with T. denticola through its adhesion/hemagglutinin domain (Hgp44). In this study, we investigated the specific domain of P. gingivalis Hgp44 responsible for adhesion to T. denticola using expression vectors harboring P. gingivalis Hgp44 DNA sequences encoding amino acid residues 1-419. Six plasmids harboring fragments in this region were generated by PCR amplification and self-ligation, and recombinant proteins r-Hgp44 (residues 1-419), r-Hgp441 (residues 1-124), r-Hgp442 (1-199), r-Hgp443 (1-316), r-Hgp444 (199-419), r-Hgp445 (124-198), and r-Hgp446 (199-316) were produced, as confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting...
May 16, 2018: Pathogens and Disease
https://www.readbyqxmd.com/read/29771176/potential-use-of-cxcl12-cxcr4-and-sonic-hedgehog-pathways-as-therapeutic-targets-in-medulloblastoma
#13
Marla Karine Amarante, Glauco Akelinghton Freire Vitiello, Marcos Henrique Rosa, Igor Alves Mancilla, Maria Angelica Ehara Watanabe
Medulloblastoma (MB) is the most common malignant brain tumor occurring in children, and although high long-term survival rates have been reached with current therapeutic protocols, several neurological injuries are still observed among survivors. It has been shown that the development of MB is highly dependent on the microenvironment surrounding it and that the CXCL12 chemokine and its receptor, CXCR4 and the Sonic Hedgehog (SHH) pathway are crucial for cerebellar development, coordinating proliferation and migration of embryonic cells and malfunctions in these axes can lead to MB development...
May 17, 2018: Acta Oncologica
https://www.readbyqxmd.com/read/29768730/biofilm-in-voice-prosthesis-a-prospective-cohort-study-and-laboratory-tests-using-sonication-and-sem-analysis
#14
Jacopo Galli, Lea Calo', Duino Meucci, Monica Giuliani, Daniela Lucidi, Gaetano Paludetti, Riccardo Torelli, Maurizio Sanguinetti, Claudio Parrilla
OBJECTIVE: The objective of the study was to compare the biofilm growing pattern and its morphological extent on silicone and a teflon-like material using a sonication process and a Scanning Electron Microscope (SEM). DESIGN: A prospective cohort study and a laboratory study. SETTING: Otolaryngology -Head and Neck surgery Department and the Microbiology Institute. PARTICIPANTS: The participants included fifteen laryngectomized patients with phonatory prostheses, which were removed due to device failure, and two different kinds of phonatory prostheses from the laboratory (Provox 2 and ActiValve) that were artificially colonized by Candida albicans...
May 16, 2018: Clinical Otolaryngology
https://www.readbyqxmd.com/read/29768039/loss-of-sonic-hedgehog-gene-leads-to-muscle-development-disorder-and-megaesophagus-in-mice
#15
Xueting Jia, Li Min, Shengtao Zhu, Shutian Zhang, Xiaofeng Huang
Sonic hedgehog ( Shh) is crucial for organogenesis in the foregut. This study investigated the function of Shh at the late-gestational stage; during which, the esophagus continues to differentiate. We established cytokeratin 14 ( CK14)-Cre;Shhfl/fl mice in which the down-regulation of Shh in the epithelium occurred at approximately the same time as esophageal muscle conversion. Hematoxylin and eosin and immunohistochemical staining, with antibodies against keratin 14, Shh, patched 1 (Ptch1), Gli1, proliferating cell nuclear antigen (PCNA), α-smooth muscle actin (αSMA), high-molecular-weight caldesmon (hCD), myogenin, paired box 7 (Pax7), β3-tubulin, and protein gene product 9...
May 16, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29764258/reference-less-mr-thermometry-on-pre-clinical-thiel-human-cadaver-for-liver-surgery-with-mrgfus
#16
Ioannis Karakitsios, Senay Mihcin, Andreas Melzer
PURPOSE: Reference-less MR thermometry can be a promising technique for temperature mapping during liver treatment with Magnetic Resonance-guided Focused Ultrasound (MRgFUS), as it is more robust to breathing motion than Proton Resonance Frequency MR thermometry. However, there is a lack of a pre-clinical model for repeatable testing of reference-less thermometry. The purpose of this work was to verify the explanted Thiel embalmed human liver and whole Thiel embalmed human cadaver for application of a custom made reference-less thermometry algorithm during MRgFUS sonication...
May 15, 2018: Minimally Invasive Therapy & Allied Technologies: MITAT
https://www.readbyqxmd.com/read/29763745/analysis-of-malondialdehyde-in-human-plasma-samples-through-derivatization-with-2-4-dinitrophenylhydrazine-by-ultrasound-assisted-dispersive-liquid-liquid-microextraction-gc-fid-approach
#17
Reyhane Malaei, Amir M Ramezani, Ghodratollah Absalan
A sensitive and reliable ultrasound-assisted dispersive liquid-liquid microextraction (UA-DLLME) procedure was developed and validated for extraction and analysis of malondialdehyde (MDA) as an important lipids-peroxidation biomarker in human plasma. In this methodology, to achieve an applicable extraction procedure, the whole optimization processes were performed in human plasma. To convert MDA into readily extractable species, it was derivatized to hydrazone structure-base by 2,4-dinitrophenylhydrazine (DNPH) at 40 °C within 60 min...
May 4, 2018: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/29762040/orally-bioavailable-and-effective-buparvaquone-lipid-based-nanomedicines-for-visceral-leishmaniasis
#18
Lindsay A Smith, Dolores Remedios Serrano, Marion Mauger, Francisco Bolás-Fernández, Maria Auxiliadora Dea-Ayuela, Aikaterini Lalatsa
Nano-enabled lipid based drug delivery systems offer a platform to overcome challenges encountered with current failed leads in the treatment of parasitic and infectious diseases. When prepared with FDA or EMA approved excipients, they can be readily translated without the need for further toxicological studies, while they remain affordable and amenable to scale-up. Buparvaquone (BPQ), a hydroxynapthoquinone with in vitro activity in the nanomolar range, failed to clinically translate as a viable treatment for visceral leishmaniasis due to its poor oral bioavailability limited by its poor aqueous solubility (BCS Class II drug)...
May 15, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29761643/fluorescent-2d-ws-2-nanosheets-bearing-chemical-affinity-elements-for-the-recognition-of-glycated-hemoglobin
#19
Jin-Kyoung Yang, Hye-Rim Lee, In-Jun Hwang, Hye-In Kim, DaBin Yim, Jong-Ho Kim
It is required to exfoliate and functionalize 2D transition metal dichalcogenides (TMDs) in an aqueous solution for biological and medical applications. Herein, the approach for the simultaneous exfoliation and functionalization of 2D WS2 nanosheets using boronic acid-modified poly(vinyl alcohol) (B-PVA) in an aqueous solution is reported, and the B-PVA-functionalized WS2 nanosheets (B-PVA-WS2 ) are exploited as a fluorescent biosensor for the detection of glycated hemoglobin, HbA1c. The synthetic B-PVA polymer facilitates the exfoliation and functionalization of WS2 nanosheets from the bulk counterpart in the aqueous solution via a pulsed sonication process, resulting in fluorescent B-PVA-WS2 nanohybrids with a specific recognition of HbA1c...
May 14, 2018: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/29760202/survey-of-human-chromosome-21-gene-expression-effects-on-early-development-in-danio-rerio
#20
Sarah Edie, Norann A Zaghloul, Carmen C Leitch, Donna K Klinedinst, Janette Lebron, Joey F Thole, Andrew S McCallion, Nicholas Katsanis, Roger H Reeves
Trisomy for human chromosome 21 (Hsa21) results in Down syndrome (DS), one of the most genetically complex conditions compatible with human survival. Assessment of the physiological consequences of dosage-driven overexpression of individual Hsa21 genes during early embryogenesis and the resulting contributions to DS pathology in mammals are not tractable in a systematic way. A recent study looked loss-of-function of C. elegans orthologues of Hsa21 genes and identified ten candidates with behavioral phenotypes, but the equivalent over-expression experiment has not been done...
May 14, 2018: G3: Genes—Genomes—Genetics
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