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https://www.readbyqxmd.com/read/28526733/discovery-and-optimization-of-hkt288-a-cadherin-6-targeting-adc-for-the-treatment-of-ovarian-and-renal-cancer
#1
Carl U Bialucha, Scott D Collins, Xiao Li, Parmita Saxena, Xiamei Zhang, Clemens Dürr, Bruno LaFont, Pierric Prieur, Yeonju Shim, Rebecca Mosher, David Lee, Lance Ostrom, Tiancen Hu, Sanela Bilic, Ivana Liric Rajlic, Vladimir Capka, Wei Jiang, Joel P Wagner, GiNell Elliott, Artur Veloso, Jessica C Piel, Meghan M Flaherty, Keith G Mansfield, Emily K Meseck, Tina Rubic-Schneider, Anne Serdakowski London, William R Tschantz, Markus Kurz, Duc Nguyen, Aaron Bourret, Matthew J Meyer, Jason E Faris, Mary J Janatpour, Vivien W Chan, Nicholas C Yoder, Kalli C Catcott, Molly A McShea, Xiuxia Sun, Hui Gao, Juliet Williams, Francesco Hofmann, Jeffrey A Engelman, Seth A Ettenberg, William R Sellers, Emma Lees
Despite an improving therapeutic landscape, significant challenges remain in treating the majority of advanced ovarian and renal cancer patients. We identified the cell-cell adhesion molecule cadherin-6 (CDH6) as a lineage gene having significant differential expression in ovarian and kidney cancer. HKT288 is an optimized CDH6-targeting DM4-based antibody drug conjugate (ADC) developed for the treatment of these diseases. Our study provides mechanistic evidence supporting the importance of linker choice for optimal anti-tumor activity and highlights CDH6 as a novel antigen for biotherapeutic development...
May 19, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28503405/nanoparticle-design-strategies-for-effective-cancer-immunotherapy
#2
Praveena Velpurisiva, Aniket Gad, Brandon Piel, Rahul Jadia, Prakash Rai
Cancer immunotherapy is a rapidly evolving and paradigm shifting treatment modality that adds a strong tool to the collective cancer treatment arsenal. It can be effective even for late stage diagnoses and has already received clinical approval. Tumors are known to not only avoid immune surveillance but also exploit the immune system to continue local tumor growth and metastasis. Because of this, most immunotherapies, particularly those directed against solid cancers, have thus far only benefited a small minority of patients...
2017: J Biomed (Syd)
https://www.readbyqxmd.com/read/28500562/epithelial-growth-factor-receptor-expression-influences-5-ala-induced-glioblastoma-fluorescence
#3
Andrea O Fontana, Deborah Piffaretti, Francesco Marchi, Floriana Burgio, Ana Bela Faia-Torres, Paolo Paganetti, Sandra Pinton, Uwe Pieles, Michael Reinert
The extent of 5-aminolevulinic acid (5-ALA) guided tumor resection has a determining impact in high-grade glioma and glioblastoma surgery. Yet the intensity of the 5-ALA induced fluorescence may vary within the tumor. We aimed to correlate 5-ALA induced fluorescence with the expression of epithelial growth factor receptor (EGFR) and its constitutively active version EGFRvIII in different glioblastoma (GBM) cell lines. To elucidate the role of EGFR in the metabolism of 5-ALA in GBM cell lines with variable EGFR expression status, we analyzed the activation of EGFR by its primary ligand EGF, and its downstream effect on Heme oxygenase-1 (HO-1), a key enzyme regulating the metabolism of Protoporphyrin IX (PpIX), the fluorescent metabolite of 5-ALA...
May 12, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28493311/ethqv6-3-is-involved-in-melon-climacteric-fruit-ripening-and-is-encoded-by-a-nac-domain-transcription-factor
#4
Pablo Ríos, Jason Argyris, Juan Vegas, Carmen Leida, Merav Kenigswald, Galil Tzuri, Christelle Troadec, Abdelhafid Bendahmane, Nurit Katzir, Belén Picó, Antonio J Monforte, Jordi Garcia-Mas
Fruit ripening is divided into climacteric and non-climacteric types depending on the presence or absence of a transient rise in respiration rate and the production of autocatalytic ethylene. Melon is ideal for the study of fruit ripening, as both climacteric and non-climacteric varieties exist. Two introgressions of the non-climacteric accession PI 161375, encompassed in the QTLs ETHQB3.5 and ETHQV6.3, into the non-climacteric "Piel de Sapo" background are able to induce climacteric ripening independently...
May 10, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28456651/development-and-evaluation-of-injectable-nanosized-drug-delivery-systems-for-apigenin
#5
Reatul Karim, Claudio Palazzo, Julie Laloy, Anne-Sophie Delvigne, Stéphanie Vanslambrouck, Christine Jerome, Elise Lepeltier, Francois Orange, Jean-Michel Dogne, Brigitte Evrard, Catherine Passirani, Géraldine Piel
The purpose of this study was to develop different injectable nanosized drug delivery systems (NDDSs) i.e. liposome, lipid nanocapsule (LNC) and polymeric nanocapsule (PNC) encapsulating apigenin (AG) and compare their characteristics to identify the nanovector(s) that can deliver the largest quantity of AG while being biocompatible. Two liposomes with different surface characteristics (cationic and anionic), a LNC and a PNC were prepared. A novel tocopherol modified poly(ethylene glycol)-b-polyphosphate block-copolymer was used for the first time for the PNC preparation...
April 27, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28448361/a-flor-de-piel
#6
Doris Salcedo
No abstract text is available yet for this article.
May 2017: American Journal of Nursing
https://www.readbyqxmd.com/read/28423290/sickle-cell-disease
#7
REVIEW
Frédéric B Piel, Martin H Steinberg, David C Rees
No abstract text is available yet for this article.
April 20, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28392155/-positional-paroxysmal-abdominal-pain
#8
M-L Piel-Julian, G Moulis, N Doumerc, P Seguin, L Astudillo, G Pugnet, L Sailler
No abstract text is available yet for this article.
April 6, 2017: La Revue de Médecine Interne
https://www.readbyqxmd.com/read/28391123/aminomethylphosphonic-acid-ampa-in-natural-waters-its-sources-behavior-and-environmental-fate
#9
REVIEW
Alexis Grandcoin, Stéphanie Piel, Estelle Baurès
The widely occurring degradation product aminomethylphosphonic acid (AMPA) is a result of glyphosate and amino-polyphosphonate degradation. Massive use of the parent compounds leads to the ubiquity of AMPA in the environment, and particularly in water. The purpose of this review is to summarize and discuss current insights into AMPA formation, transport, persistence and toxicity. In agricultural soils, AMPA is concentrated in the topsoil, and degrades slowly in most soils. It can reach shallow groundwater, but rarely managed to enter deep groundwater...
June 15, 2017: Water Research
https://www.readbyqxmd.com/read/28371720/whole-blood-microsampling-for-the-quantitation-of-estetrol-without-derivatization-by-liquid-chromatography-tandem-mass-spectrometry
#10
Gwenaël Nys, Anne Gallez, Miranda G M Kok, Gaël Cobraiville, Anne-Catherine Servais, Géraldine Piel, Christel Pequeux, Marianne Fillet
Quantitative bioanalysis and especially pharmacokinetic studies are challenging since only low volumes of biological material are available and low concentrations (ng/ml) are often expected. In this context, volumetric absorptive microsampling (VAMS) devices were developed to accurately collect 10 or 20μl of whole blood from tested subjects. In this study, we present the development and validation of ultra-high performance liquid chromatography coupled to tandem mass spectrometry method after VAMS sampling for the quantitation of estetrol (E4), a potentially new medicine for hormone replacement, contraception and osteoporosis therapies...
June 5, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28370791/cyanobacterial-ent-sterol-like-natural-products-from-a-deviated-ubiquinone-pathway
#11
Philipp Moosmann, Reiko Ueoka, Laura Grauso, Alfonso Mangoni, Brandon I Morinaka, Muriel Gugger, Jörn Piel
Natural products from marine animals show high potential for the development of new medicines, but drug development based on these compounds is commonly hampered by their low natural abundance. Since many of these metabolites are suspected or known to be produced by uncultivated bacterial symbionts, the rapidly growing diversity of sequenced prokaryotic genomes offers the opportunity to identify alternative, culturable sources of natural products computationally. In this work, we investigated the potential of using this sequenced resource to facilitate the production of meroterpenoid-like compounds related to those from marine sources...
March 30, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28370685/non-invasive-quantification-of-ethylene-in-attached-fruit-headspace-at-1%C3%A2-p-p-b-by-gas-chromatography-mass-spectrometry
#12
Lara Pereira, Marta Pujol, Jordi Garcia-Mas, Michael A Phillips
Ethylene is a gaseous plant hormone involved in defense, adaptations to environmental stress and fruit ripening. Its relevance to the latter makes its detection highly useful for physiologists interested in the onset of ripening. Produced as a sharp peak during the respiratory burst, ethylene is biologically active at tens of nl L(-1) . Reliable quantification at such concentrations generally requires specialized instrumentation. Here we present a rapid, high-sensitivity method for detecting ethylene in attached fruit using a conventional gas chromatography-mass spectrometry (GC-MS) system and in situ headspace collection chambers...
March 28, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28363973/electrical-and-structural-adaptations-of-the-paediatric-athlete-s-heart-a-systematic-review-with-meta-analysis
#13
REVIEW
Gavin McClean, Nathan R Riding, Clare L Ardern, Abdulaziz Farooq, Guido E Pieles, Victoria Watt, Carmen Adamuz, Keith P George, David Oxborough, Mathew G Wilson
AIM: To describe the electrocardiographic (ECG) and echocardiographic manifestations of the paediatric athlete's heart, and examine the impact of age, race and sex on cardiac remodelling responses to competitive sport. DESIGN: Systematic review with meta-analysis. DATA SOURCES: Six electronic databases were searched to May 2016: MEDLINE, PubMed, EMBASE, Web of Science, CINAHL and SPORTDiscus. INCLUSION CRITERIA: (1) Male and/or female competitive athletes, (2) participants aged 6-18 years, (3) original research article published in English language...
March 31, 2017: British Journal of Sports Medicine
https://www.readbyqxmd.com/read/28350964/promoting-vaginal-distribution-of-e7-and-mcl-1-sirna-silencing-nanoparticles-for-cervical-cancer-treatment
#14
Anna Lechanteur, Tania Furst, Brigitte Evrard, Philippe Delvenne, Géraldine Piel, Pascale Hubert
There is an urgent need to develop a less aggressive and more effective treatment against cervical lesions induced by different high-risk human papillomavirus (HR-HPV). We investigated the potential of a cocktail of small interfering RNA (siRNA) directed against the oncoprotein E6 (E6), the oncoprotein E7 (E7), or the antiapoptotic protein MCL-1 (MCL-1). The combination of siRNA anti-E7 and anti-MCL-1 demonstrated high efficacy on multiple HPV16 and HPV18 cell lines and no effects on healthy keratinocytes. This gene therapy has been considered for a vaginal administration since this route of application holds high potential for the treatment of diseases in the female reproductive tracts...
April 7, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28346861/biomimetic-remineralization-of-carious-lesions-by-self-assembling-peptide
#15
L Kind, S Stevanovic, S Wuttig, S Wimberger, J Hofer, B Müller, U Pieles
Caries is the most common disease in the world. Great efforts have been undertaken for prevention and to identify a regenerative treatment solution for dental caries. Self-assembling β-sheet forming peptides have previously shown to form 3-dimensional fiber networks supporting tissue regeneration. In particular, the self-assembling peptide P11-4 has shown potential in the treatment and prevention of dental caries. It has previously been shown that application of monomeric P11-4 solution to early carious lesions can increase net mineral gain by forming de novo hydroxyapatite crystals...
March 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28338684/seven-enzymes-create-extraordinary-molecular-complexity-in-an-uncultivated-bacterium
#16
Michael F Freeman, Maximilian J Helf, Agneya Bhushan, Brandon I Morinaka, Jörn Piel
Uncultivated bacteria represent a massive resource of new enzymes and bioactive metabolites, but such bacteria remain functionally enigmatic. Polytheonamides are potent peptide cytotoxins produced by uncultivated bacteria that exist as symbionts in a marine sponge. Outside glycobiology, polytheonamides represent the most heavily post-translationally modified biomolecules that are derived from amino acids. The biosynthesis of polytheonamides involves up to 50 site-specific modifications to create a membrane-spanning β-helical structure...
April 2017: Nature Chemistry
https://www.readbyqxmd.com/read/28335663/universal-and-particular-in-morphological-processing-evidence-from-hebrew
#17
Yael Farhy, João Veríssimo, Harald Clahsen
Do properties of individual languages shape the mechanisms by which they are processed? By virtue of their non-concatenative morphological structure, the recognition of complex words in Semitic languages has been argued to rely strongly on morphological structure and decomposition into root and pattern constituents. Here, we report results from a masked priming experiment in Hebrew in which we contrasted verb forms belonging to two morphological classes, Paal and Piel, which display similar properties, but crucially differ on whether they are extended to novel verbs...
March 24, 2017: Quarterly Journal of Experimental Psychology: QJEP
https://www.readbyqxmd.com/read/28329500/lesi%C3%A3-n-cribiforme-en-la-cara-de-un-var%C3%A3-n-de-44-a%C3%A3-os-de-edad
#18
Romina Rodriguez-Lojo, Iria Castiñeiras, Olga Robles, Mercedes Otero, Yolanda Juarez, Mercedes Lueiro, Maria-Luisa Fernandez-Diaz
El acantoma de la vaina pilosa es un tumor benignode piel muy poco frecuente. Suele presentarse comouna pápula asintomática, con un orificio central y lalocalización más frecuente es la cara. Presentamos unnuevo caso de acantoma de vaina pilosa, apoartandoimagen dermatoscópica del tumor.
February 15, 2017: Dermatology Online Journal
https://www.readbyqxmd.com/read/28290537/compact-silicon-multimode-waveguide-spectrometer-with-enhanced-bandwidth
#19
Molly Piels, Darko Zibar
Compact, broadband, and high-resolution spectrometers are appealing for sensing applications, but difficult to fabricate. Here we show using calibration data a spectrometer based on a multimode waveguide with 2 GHz resolution, 250 GHz bandwidth, and a 1.6 mm × 2.1 mm footprint. Typically, such spectrometers have a bandwidth limited by the number of modes supported by the waveguide. In this case, an on-chip mode-exciting element is used to repeatably excite distinct collections of waveguide modes...
March 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28238042/entotheonella-bacteria-as-source-of-sponge-derived-natural-products-opportunities-for-biotechnological-production
#20
Agneya Bhushan, Eike E Peters, Jörn Piel
Marine sponges belong to the oldest animals existing today. Apart from their role in recycling of carbon and nitrogen in the ocean, they are also an important source of a wide variety of structurally diverse bioactive natural products. Over the past few decades, a multitude of compounds from sponges have been discovered exhibiting diverse, pharmacologically promising activities. However, in many cases the low substance quantities present in the sponge tissue would require the collection of large amounts of sponge material, thus impeding further drug development...
2017: Progress in Molecular and Subcellular Biology
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