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https://www.readbyqxmd.com/read/28429197/axillary-micrometastases-and-isolated-tumor-cells-are-not-an-indication-for-post-mastectomy-radiotherapy-in-stage-1-and-2-breast-cancer
#1
Anita Mamtani, Sujata Patil, Michelle Stempel, Monica Morrow
BACKGROUND: Randomized trials demonstrate equivalent locoregional control with sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND) for T1-2 micrometastatic breast cancer, but include few mastectomy patients. Consensus is lacking on indications for post-mastectomy radiotherapy (PMRT) in this population. Herein, we evaluate locoregional recurrence (LRR) in an unselected, modern cohort of T1-2 breast cancer patients with micrometastases or isolated tumor cells (ITCs; N0i+/N1mi) having a mastectomy...
April 20, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28427004/enzymatic-activity-of-the-cam-pde1-system-upon-addition-of-actinyl-ions
#2
Florian Brulfert, Samir Safi, Aurélie Jeanson, Harald Foerstendorf, Stephan Weiss, Catherine Berthomieu, Sandrine Sauge-Merle, Éric Simoni
The threat of a dirty bomb which could cause internal contamination has been of major concern for the past decades. Because of their high chemical toxicity and their presence in the nuclear fuel cycle, uranium and neptunium are two actinides of high interest. Calmodulin (CaM) which is a ubiquitous protein present in all eukaryotic cells and is involved in calcium-dependent signaling pathways has a known affinity for uranyl and neptunyl ions. The impact of the complexation of these actinides on the physiological response of the protein remains, however, largely unknown...
April 8, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28424370/multi-site-binding-of-epigallocatechin-gallate-to-human-serum-albumin-measured-by-nmr-and-isothermal-calorimetry
#3
Joshua D Eaton, Mike P Williamson
The affinity of epigallocatechin gallate (EGCG) for human serum albumin was measured in physiological conditions using nuclear magnetic resonance (NMR) and isothermal titration calorimetry (ITC). NMR estimated the self-dissociation constant of EGCG as 50 mM. NMR showed two binding events: strong (n1 = 1.8 ± 0.2; Kd1 = 19 ± 12 μM), and weak (n2 ~ 20; Kd2 = 40 ± 20 mM). ITC also showed two binding events: strong (n1 = 2.5 ± 0.03; Kd1 = 21.6 ± 4.0 μM), and weak (n2 = 9 ± 1; Kd2 = 22 ± 4 mM). The two techniques are consistent, with an unexpectedly high number of bound EGCG...
April 19, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28423681/sulforaphane-for-the-chemoprevention-of-bladder-cancer-molecular-mechanism-targeted-approach
#4
REVIEW
Andrew Leone, Gregory Diorio, Wade Sexton, Michael Schell, Mark Alexandrow, Jed W Fahey, Nagi B Kumar
The clinical course for both early and late stage Bladder Cancer (BC) continues to be characterized by significant patient burden due to numerous occurrences and recurrences requiring frequent surveillance strategies, intravesical drug therapies, and even more aggressive treatments in patients with locally advanced or metastatic disease. For these reasons, BC is also the most expensive cancer to treat. Fortunately, BC offers an excellent platform for chemoprevention interventions with potential to optimize the systemic and local exposure of promising agents to the bladder mucosa...
March 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28420412/intersect-then-combine-approach-improving-the-performance-of-somatic-variant-calling-in-whole-exome-sequencing-data-using-multiple-aligners-and-callers
#5
Maurizio Callari, Stephen-John Sammut, Leticia De Mattos-Arruda, Alejandra Bruna, Oscar M Rueda, Suet-Feung Chin, Carlos Caldas
Bioinformatic analysis of genomic sequencing data to identify somatic mutations in cancer samples is far from achieving the required robustness and standardisation. In this study we generated a whole exome sequencing benchmark dataset using the platinum genome sample NA12878 and developed an intersect-then-combine (ITC) approach to increase the accuracy in calling single nucleotide variants (SNVs) and indels in tumour-normal pairs. We evaluated the effect of alignment, base quality recalibration, mutation caller and filtering on sensitivity and false positive rate...
April 18, 2017: Genome Medicine
https://www.readbyqxmd.com/read/28414426/two-distinct-assembly-states-of-cysteine-regulatory-complex-of-salmonella-typhimurium-are-regulated-by-enzyme-substrate-cognate-pairs
#6
Abhishek Kaushik, Mary Krishna Ekka, Sangaralingam Kumaran
Serine acetyltransferase (SAT) and O-acetylserine sulfhydrylase (OASS), which catalyze last two steps of cysteine biosynthesis, interact and form Cysteine Regulatory Complex (CRC). The current model of Salmonella typhimurium predicts that CRC is composed of one [SAT]hexmer unit and two molecules of [OASS]dimer. However, it is not clear why [SAT]hexamer can not engage all of its six high-affinity binding sites. We examined the assembly state(s) of CRC by size exclusion chromatography (SEC), analytical ultracentrifugation (AUC), isothermal titration calorimetry (ITC), and surface plasmon resonance (SPR) approaches...
April 17, 2017: Biochemistry
https://www.readbyqxmd.com/read/28414235/bis-heteroleptic-ruthenium-ii-complex-of-pendant-urea-functionalized-pyridyl-triazole-and-phenathroline-for-recognition-sensing-and-extraction-of-oxyanions
#7
Tamal Kanti Ghosh, Sourav Chakraborty, Bijit Chowdhury, Pradyut Ghosh
A new bis-heteroleptic Ru(II) complex based ditopic receptor, 1[PF6]2, having an anion binding triazole -CH unit and appended 4-fluorophenyl urea arm has been developed. (1)H NMR and isothermal titration calorimetry (ITC) experiments showed binding of 1[PF6]2 toward oxyanions such as phosphates (e.g., H2PO4(-) and HP2O7(3-)) and carboxylates (e.g., CH3CO2(-) and C6H5CO2(-)) anions selectively. (1)H NMR studies showed that highly basic phosphate anions such as HP2O7(3-)/H2PO4(-) are bound by both -CH and -NH units of complex 1[PF6]2...
April 17, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28414138/apigenin-a-modulator-of-ppar%C3%AE-attenuates-hfd-induced-nafld-by-regulating-hepatocyte-lipid-metabolism-and-oxidative-stress-via-nrf2-activation
#8
Xiujing Feng, Wen Yu, Xinda Li, Feifei Zhou, Wenlong Zhang, Qi Shen, Jianxin Li, Can Zhang, Pingping Shen
Lipid metabolic disorders and oxidative stress in the liver are key steps in the progression of nonalcoholic fatty liver disease (NAFLD), which is a major risk factor for the development of metabolic syndrome. To date, no pharmacological treatment for this condition has been approved. Our previous study has found that the food-derived compound apigenin (Api) significantly attenuates obesity-induced metabolic syndrome by acting as a peroxisome proliferator-activated receptor gamma modulator (PPARM). Herein, a high fat diet (HFD) induced NAFLD model was used to dig out whether Api had the effect on NAFLD...
April 13, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28411273/low-frequency-cortical-oscillations-entrain-to-sub-threshold-rhythmic-auditory-stimuli
#9
Sanne Ten Oever, Charles E Schroeder, David Poeppel, Nienke van Atteveldt, Ashesh D Mehta, Pierre Mégevand, David M Groppe, Elana Zion-Golumbic
Many environmental stimuli contain temporal regularities, a feature which can help predict forthcoming input. Phase-locking (entrainment) of ongoing low-frequency neuronal oscillations to rhythmic stimuli is proposed as a potential mechanism for enhancing neuronal responses and perceptual sensitivity, by aligning high-excitability phases to events within a stimulus stream. Previous experiments show that rhythmic structure has a behavioral benefit even when the rhythm itself is below perceptual detection thresholds (Ten Oever et al...
April 14, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28400581/rational-development-of-stafib-2-a-selective-nanomolar-inhibitor-of-the-transcription-factor-stat5b
#10
Nagarajan Elumalai, Angela Berg, Stefan Rubner, Linda Blechschmidt, Chen Song, Kalaiselvi Natarajan, Jörg Matysik, Thorsten Berg
The transcription factor STAT5b is a target for tumour therapy. We recently reported catechol bisphosphate and derivatives such as Stafib-1 as the first selective inhibitors of the STAT5b SH2 domain. Here, we demonstrate STAT5b binding of catechol bisphosphate by solid-state nuclear magnetic resonance, and report on rational optimization of Stafib-1 (Ki = 44 nM) to Stafib-2 (Ki = 9 nM). The binding site of Stafib-2 was validated using combined isothermal titration calorimetry (ITC) and protein point mutant analysis, representing the first time that functional comparison of wild-type versus mutant protein by ITC has been used to characterize the binding site of a small-molecule ligand of a STAT protein with amino acid resolution...
April 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28394276/targeting-colorectal-cancer-proliferation-stemness-and-metastatic-potential-using-brassicaceae-extracts-enriched-in-isothiocyanates-a-3d-cell-model-based-study
#11
Lucília P Pereira, Patrícia Silva, Marlene Duarte, Liliana Rodrigues, Catarina M M Duarte, Cristina Albuquerque, Ana Teresa Serra
Colorectal cancer (CRC) recurrence is often attributable to circulating tumor cells and/or cancer stem cells (CSCs) that resist to conventional therapies and foster tumor progression. Isothiocyanates (ITCs) derived from Brassicaceae vegetables have demonstrated anticancer effects in CRC, however little is known about their effect in CSCs and tumor initiation properties. Here we examined the effect of ITCs-enriched Brassicaceae extracts derived from watercress and broccoli in cell proliferation, CSC phenotype and metastasis using a previously developed three-dimensional HT29 cell model with CSC-like traits...
April 10, 2017: Nutrients
https://www.readbyqxmd.com/read/28394186/early-adolescent-language-development-following-intrathecal-chemotherapy-for-acute-lymphoblastic-leukaemia
#12
Fiona M Lewis, Jaycie K Bohan
PURPOSE: Central nervous system (CNS) prophylaxis in the treatment of childhood acute lymphoblastic leukaemia (ALL) is routinely achieved through intrathecal chemotherapy (ITC). The presence of high level language deficits in older children who received CNS-directed ITC for ALL in early childhood is yet to be elucidated, with previous research suggesting that high level language deficits may appear later in ALL survivors' development at an age when these skills typically emerge. METHOD: A test battery covering foundational language skills and higher-order language skills was administered to five participants (aged 10-15 years) with a history of ITC for ALL...
April 10, 2017: International Journal of Speech-language Pathology
https://www.readbyqxmd.com/read/28393280/nmr-line-shape-analysis-of-a-multi-state-ligand-binding-mechanism-in-chitosanase
#13
Shoko Shinya, Mariana G Ghinet, Ryszard Brzezinski, Kyoko Furuita, Chojiro Kojima, Sneha Shah, Evgenii L Kovrigin, Tamo Fukamizo
Chitosan interaction with chitosanase was examined through analysis of spectral line shapes in the NMR HSQC titration experiments. We established that the substrate, chitosan hexamer, binds to the enzyme through the three-state induced-fit mechanism with fast formation of the encounter complex followed by slow isomerization of the bound-state into the final conformation. Mapping of the chemical shift perturbations in two sequential steps of the mechanism highlighted involvement of the substrate-binding subsites and the hinge region in the binding reaction...
April 9, 2017: Journal of Biomolecular NMR
https://www.readbyqxmd.com/read/28390975/natural-isothiocyanates-express-antimicrobial-activity-against-developing-and-mature-biofilms-of-pseudomonas-aeruginosa
#14
Stefan J Kaiser, Nico T Mutters, Brigitte Blessing, Frank Günther
BACKGROUND: The antimicrobial properties of natural isothiocyanates (ITCs) found in plants such as nasturtium (Tropaeolum majus) and horseradish (Armoracia rusticana), and the need of new chemotherapeutic options for treatment of infections caused by multidrug-resistant and biofilm-forming Gram-negative bacteria such as Pseudomonas aeruginosa (Pa), led us to evaluate the effects of three major ITCs, allylisothiocyanate (AITC), benzylisothiocyanate (BITC), and phenylethyl-isothiocyanate (PEITC), and a mixture (ITCM) adapted to the ITC composition after release of active components out of natural sources...
April 5, 2017: Fitoterapia
https://www.readbyqxmd.com/read/28389333/the-thermodynamic-signature-of-ligand-binding-to-histone-deacetylase-like-amidohydrolases-is-most-sensitive-to-the-flexibility-in-the-l2-loop-lining-the-active-site-pocket
#15
Christian Meyners, Andreas Krämer, Özkan Yildiz, Franz-Josef Meyer-Almes
BACKGROUND: The analysis of the thermodynamic driving forces of ligand-protein binding has been suggested to be a key component for the selection and optimization of active compounds into drug candidates. The binding enthalpy as deduced from isothermal titration calorimetry (ITC) is usually interpreted assuming single-step binding of a ligand to one conformation of the target protein. Although successful in many cases, these assumptions are oversimplified approximations of the reality with flexible proteins and complicated binding mechanism in many if not most cases...
April 4, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28387850/nicotine-metabolite-ratio-nmr-prospectively-predicts-smoking-relapse-longitudinal-findings-from-itc-surveys-in-five-countries
#16
Brian V Fix, Richard J O'Connor, Neal Benowitz, Bryan W Heckman, K Michael Cummings, Geoffrey T Fong, James F Thrasher
Introduction: The ratio of trans 3'-hydroxycotinine (3HC) to cotinine (nicotine metabolite ratio, NMR) is a biomarker of the rate of nicotine metabolism, with higher NMR indicating faster metabolism. Higher NMR has been found to be associated with higher daily cigarette consumption and less success stopping smoking in cessation trials. This study examines differences in NMR among population-based samples of smokers in the 5 countries and explores the relationship between NMR and smoking abstinence...
April 6, 2017: Nicotine & Tobacco Research: Official Journal of the Society for Research on Nicotine and Tobacco
https://www.readbyqxmd.com/read/28380300/biophysical-study-on-the-interaction-between-eperisone-hydrochloride-and-human-serum-albumin-using-spectroscopic-calorimetric-and-molecular-docking-analysis
#17
Gulam Rabbani, Mohammad Hassan Baig, Eun Ju Lee, Won Kyung Cho, Jin Yeul Ma, Inho Choi
Eperisone hydrochloride (EH) is a widely used as a muscle relaxant for patients with muscular contracture, low back pain, or spasticity. Human serum albumin (HSA), a highly soluble negatively charged, endogenous and abundant plasma protein ascribed with the ligand binding and transport properties. The current study was undertaken to explore the interaction between EH and the serum transport protein, HSA. Study of the interaction between HSA and EH was carried by UV-vis, fluorescence quenching, circular dichroism (CD) spectroscopy, FRET, and ITC...
April 5, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28377272/interactions-and-release-of-two-palmitoyl-peptides-from-phytantriol-cubosomes
#18
Seyedeh Parinaz Akhlaghi, Watson Loh
Phytantriol cubosomes loaded with two palmitoyl peptides (Palpepcubes), namely GHKcube and GQPRcube, were prepared using an ultrasonication protocol. The Palpepcubes dimensions were characterized by dynamic light scattering (DLS) and cryo-transmission electron microscopy (cryo-TEM). Small-angle X-ray scattering (SAXS) analyses revealed that the bicontinuous cubic structure remained even at palmitoyl peptide contents as high as 5 wt.%, with an increase in the cell parameter from approximately 6.5 to 7.2 nm. Isothermal titration calorimetry (ITC) was used to elucidate the interactions between the blank cubosomes and the palmitoyl peptides, revealing an exothermic process of interaction...
April 1, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28362093/selective-and-robust-stabilization-of-triplex-dna-structures-using-cationic-comb-type-copolymers
#19
Asako Yamayoshi, Daisuke Miyoshi, Yu-Ki Zouzumi, Yohei Matsuyama, Jumpei Ariyoshi, Naohiko Shimada, Akira Murakami, Takehiko Wada, Atsushi Maruyama
DNA sequences capable of forming triplexes induce DNA double-strand breaks that have attracted attention in genome editing technologies (e.g., CRISPR/Cas9 system, TALEN, and ZFN). Therefore, novel functional tools that stabilize triplex DNA structures must be further investigated to spark renewed interest. In this study, we investigated the unique character of cationic comb-type copolymers for the selective stabilization of triplex DNA. The melting temperature (Tm) of triplex DNA increased from 24.5 ºC to 73...
March 31, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28358124/domain-specific-interactions-between-mln8237-and-human-serum-albumin-estimated-by-std-and-waterlogsy-nmr-itc-spectroscopic-and-docking-techniques
#20
Hongqin Yang, Jiuyang Liu, Yanmei Huang, Rui Gao, Bin Tang, Shanshan Li, Jiawei He, Hui Li
Alisertib (MLN8237) is an orally administered inhibitor of Aurora A kinase. This small-molecule inhibitor is under clinical or pre-clinical phase for the treatment of advanced malignancies. The present study provides a detailed characterization of the interaction of MLN8237 with a drug transport protein called human serum albumin (HSA). STD and WaterLOGSY nuclear magnetic resonance (NMR)-binding studies were conducted first to confirm the binding of MLN8237 to HSA. In the ligand orientation assay, the binding sites of MLN8237 were validated through two site-specific spy molecules (warfarin sodium and ibuprofen, which are two known site-selective probes) by using STD and WaterLOGSY NMR competition techniques...
March 30, 2017: Scientific Reports
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