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https://www.readbyqxmd.com/read/28212557/using-high-sensitivity-sequencing-for-the-detection-of-mutations-in-btk-and-plc%C3%AE-2-genes-in-cellular-and-cell-free-dna-and-correlation-with-progression-in-patients-treated-with-btk-inhibitors
#1
Adam Albitar, Wanlong Ma, Ivan DeDios, Jeffrey Estella, Inhye Ahn, Mohammed Farooqui, Adrian Wiestner, Maher Albitar
Patients with chronic lymphocytic leukemia (CLL) that develop resistance to Bruton tyrosine kinase (BTK) inhibitors are typically positive for mutations in BTK or phospholipase c gamma 2 (PLCγ2). We developed a high sensitivity (HS) assay utilizing wild-type blocking polymerase chain reaction achieved via bridged and locked nucleic acids. We used this high sensitivity assay in combination with Sanger sequencing and next generation sequencing (NGS) and tested cellular DNA and cell-free DNA (cfDNA) from patients with CLL treated with the BTK inhibitor, ibrutinib...
February 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212536/targeting-the-stress-oncoprotein-ledgf-p75-to-sensitize-chemoresistant-prostate-cancer-cells-to-taxanes
#2
Leslimar Ríos-Colón, Christina K Cajigas-Du Ross, Anamika Basu, Catherine Elix, Ivana Alicea-Polanco, Tino W Sanchez, Vinodh Radhakrishnan, Chien-Shing Chen, Carlos A Casiano
Prostate cancer (PCa) is associated with chronic prostate inflammation resulting in activation of stress and pro-survival pathways that contribute to disease progression and chemoresistance. The stress oncoprotein lens epithelium-derived growth factor p75 (LEDGF/p75), also known as DFS70 autoantigen, promotes cellular survival against environmental stressors, including oxidative stress, radiation, and cytotoxic drugs. Furthermore, LEDGF/p75 overexpression in PCa and other cancers has been associated with features of tumor aggressiveness, including resistance to cell death and chemotherapy...
February 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212528/the-crispr-cas9%C3%A2-system-efficiently-reverts-the-tumorigenic-ability-of-bcr-abl-in-vitro-and-in-a-xenograft-model-of-chronic-myeloid-leukemia
#3
Ignacio García-Tuñón, María Hernández-Sánchez, José Luis Ordoñez, Veronica Alonso-Pérez, Miguel Álamo-Quijada, Rocio Benito, Carmen Guerrero, Jesús María Hernández-Rivas, Manuel Sánchez-Martín
CRISPR/Cas9 technology was used to abrogate p210 oncoprotein expression in the Boff-p210 cell line, a pro-B line derived from interlukin-3-dependent Baf/3, that shows IL-3-independence arising from the constitutive expression of BCR-ABL p210. Using this approach, pools of Boff-p210-edited cells and single edited cell-derived clones were obtained and functionally studied in vitro. The loss of p210 expression in Boff-p210 cells resulted in the loss of ability to grow in the absence of IL-3, as the Baf/3 parental line, showing significantly increased apoptosis levels...
February 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212512/are-antifouling-paint-particles-a-continuous-source-of-toxic-chemicals-to-the-marine-environment
#4
Sanye Soroldoni, Fiamma Abreu, Ítalo Braga Castro, Fabio Andrei Duarte, Grasiela Lopes Leães Pinho
Antifouling paint particles (APPs) are generated during periodical maintenance of boat hulls. Chemical composition and toxicity (either chronic or acute) of APPs found in the sediment was evaluated using the epibenthic copepod Nitokra sp. The APPs analyzed showed the presence of high levels of metals such as Cu (234,247±268μgg(-1)), Zn (112,404±845μgg(-1)) and the booster biocide DCOIT (0.13μgg(-1)). Even at low concentrations (as from 5mgg(-1) of APPs by mass of sediment) a significantly decrease in the fecundity was observed in laboratory tests...
February 3, 2017: Journal of Hazardous Materials
https://www.readbyqxmd.com/read/28212483/-correlation-of-heart-rate-variability-with-syntax-ii-on-chronic-angina
#5
Tatiana Chantal Castro-de la Torre, Norma Amador-Licona, Enrique Bernal-Ruíz
BACKGROUND: The heart rate variability (HRV) is a prognostic value of cardiovascular risk. It is unknown the correlation between HRV and coronary severity on patients with chronic angina. The objective was to determine the correlation between HRV and the SYNTAX II score in chronic angina. METHODS: Cross-sectional study in patients of 18 years or older with stable angina and indication of coronary angiography who went to a third level center. The SYNTAX II score was established by using coronary angiography, while HRV was obtained by a 24-hour Holter ECG...
2017: Revista Médica del Instituto Mexicano del Seguro Social
https://www.readbyqxmd.com/read/28212463/efficacy-and-tolerability-of-an-inhaled-selective-glucocorticoid-receptor-modulator-azd5423-in-copd-patients-phase-ii-study-results
#6
Piotr Kuna, Magnus Aurivillius, Carin Jorup, Susanne Prothon, Ziad Taib, Staffan Edsbäcker
AZD5423 is a novel, inhaled, selective glucocorticoid receptor modulator (SGRM), which in an allergen challenge model in asthmatics improved lung function and airway hyper-reactivity. In the current trial, AZD5423 was for the first time tested in patients with chronic obstructive pulmonary disease (COPD). In this double-blind, randomised and parallel group study, we examined airway and systemic effects of two doses of AZD5423, inhaled via Turbuhaler for 12 weeks, in 353 symptomatic COPD patients (average pre-bronchodilator forced expiratory volume in one second (FEV1) at screening was 50-52% of predicted normal)...
February 17, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28212436/antibody-deficiency-in-patients-with-frequent-exacerbations-of-chronic-obstructive-pulmonary-disease-copd
#7
Brian N McCullagh, Alejandro P Comellas, Zuhair K Ballas, John D Newell, M Bridget Zimmerman, Antoine E Azar
Chronic Obstructive Pulmonary Disease is the third leading cause of death in the US, and is associated with periodic exacerbations, which account for the largest proportion of health care utilization, and lead to significant morbidity, mortality, and worsening lung function. A subset of patients with COPD have frequent exacerbations, occurring 2 or more times per year. Despite many interventions to reduce COPD exacerbations, there is a significant lack of knowledge in regards to their mechanisms and predisposing factors...
2017: PloS One
https://www.readbyqxmd.com/read/28212415/aflatoxin-exposure-during-the-first-36-months-of-life-was-not-associated-with-impaired-growth-in-nepalese-children-an-extension-of-the-mal-ed-study
#8
Nicole J Mitchell, Hui-Husan Hsu, Ram Krishna Chandyo, Binob Shrestha, Ladaporn Bodhidatta, Yu-Kang Tu, Yun-Yun Gong, Patricia A Egner, Manjeswori Ulak, John D Groopman, Felicia Wu
Exposure to aflatoxin, a mycotoxin common in many foods, has been associated with child growth impairment in sub-Saharan Africa. To improve our understanding of growth impairment in relation to aflatoxin and other risk factors, we assessed biospecimens collected in Nepalese children at 15, 24, and 36 months of age for aflatoxin exposure. Children (N = 85) enrolled in the Bhaktapur, Nepal MAL-ED study encompassed the cohort analysed in this study. Exposure was assessed through a plasma biomarker of aflatoxin exposure: the AFB1-lysine adduct...
2017: PloS One
https://www.readbyqxmd.com/read/28212407/epidemiology-of-low-proteinuric-chronic-kidney-disease-in-renal-clinics
#9
Luca De Nicola, Michele Provenzano, Paolo Chiodini, Silvio Borrelli, Luigi Russo, Antonio Bellasi, Domenico Santoro, Giuseppe Conte, Roberto Minutolo
CKD patients with low-grade proteinuria (LP) are common in nephrology clinics. However, prevalence, characteristics, and the competing risks of ESRD and death as the specific determinants, are still unknown. We analyzed epidemiological features of LP status in a prospective cohort of 2,340 patients with CKD stage III-V referred from ≥6 months in 40 nephrology clinics in Italy. LP status was defined as proteinuria <0.5 g/24h according to current KDIGO guidelines. Patients with higher proteinuria constituted the control group (CON)...
2017: PloS One
https://www.readbyqxmd.com/read/28212395/delayed-apoptosis-allows-islet-%C3%AE-cells-to-implement-an-autophagic-mechanism-to-promote-cell-survival
#10
Heather L Hayes, Brett S Peterson, Jonathan M Haldeman, Christopher B Newgard, Hans E Hohmeier, Samuel B Stephens
Increased β-cell death coupled with the inability to replicate existing β-cells drives the decline in β-cell mass observed in the progression of both major forms of diabetes. Understanding endogenous mechanisms of islet cell survival could have considerable value for the development of novel strategies to limit β-cell loss and thereby promote β-cell recovery. Insulinoma cells have provided useful insight into β-cell death pathways but observations made in cell lines sometimes fail to translate to primary islets...
2017: PloS One
https://www.readbyqxmd.com/read/28212359/considerations-in-the-frontline-treatment-of-chronic-lymphocytic-leukemia
#11
Susan M O'Brien
No abstract text is available yet for this article.
December 2016: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/28212341/physicochemical-characterization-and-biological-activities-of-the-triterpenic-mixture-%C3%AE-%C3%AE-amyrenone
#12
Rosilene G S Ferreira, Walter F Silva Júnior, Valdir F Veiga Junior, Ádley A N Lima, Emerson S Lima
α-Amyrenone and β-amyrenone are triterpenoid isomers that occur naturally in very low concentrations in several oleoresins from Brazilian Amazon species of Protium (Burseraceae). This mixture can also be synthesized by oxidation of α,β-amyrins, obtained as major compounds from the same oleoresins. Using a very simple, high yield procedure, and using a readily commercially available mixture of α,β-amyrins as substrate, the binary compound α,β-amyrenone was synthesized and submitted to physico-chemical characterization using different techniques such as high-performance liquid chromatography, nuclear magnetic resonance (¹H and (13)C), mass spectrometry, scanning electron microscopy, differential scanning calorimetry, thermogravimetry and derivative thermogravimetry, and Fourier transform infrared spectroscopy (FTIR)...
February 16, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28212332/type-1-diabetes-candidate-genes-linked-to-pancreatic-islet-cell-inflammation-and-beta-cell-apoptosis
#13
REVIEW
Joachim Størling, Flemming Pociot
Type 1 diabetes (T1D) is a chronic immune-mediated disease resulting from the selective destruction of the insulin-producing pancreatic islet β-cells. Susceptibility to the disease is the result of complex interactions between environmental and genetic risk factors. Genome-wide association studies (GWAS) have identified more than 50 genetic regions that affect the risk of developing T1D. Most of these susceptibility loci, however, harbor several genes, and the causal variant(s) and gene(s) for most of the loci remain to be established...
February 16, 2017: Genes
https://www.readbyqxmd.com/read/28212318/alcohol-%C3%A2-adipose%C3%A2-tissue%C3%A2-and%C3%A2-lipid%C3%A2-dysregulation
#14
Jennifer L Steiner, Charles H Lang
Chronic alcohol consumption perturbs lipid metabolism as it increases adipose tissue lipolysis and leads to ectopic fat deposition within the liver and the development of alcoholic fatty liver disease. In addition to the recognition of the role of adipose tissue derived fatty acids in liver steatosis, alcohol also impacts other functions of adipose tissue and lipid metabolism. Lipid balance in response to long-term alcohol intake favors adipose tissue loss and fatty acid efflux as lipolysis is upregulated and lipogenesis is either slightly decreased or unchanged...
February 16, 2017: Biomolecules
https://www.readbyqxmd.com/read/28212315/developmental-programming-of-adult-disease-reprogramming-by-melatonin
#15
REVIEW
You-Lin Tain, Li-Tung Huang, Chien-Ning Hsu
Adult-onset chronic non-communicable diseases (NCDs) can originate from early life through so-called the "developmental origins of health and disease" (DOHaD) or "developmental programming". The DOHaD concept offers the "reprogramming" strategy to shift the treatment from adulthood to early life, before clinical disease is apparent. Melatonin, an endogenous indoleamine produced by the pineal gland, has pleiotropic bioactivities those are beneficial in a variety of human diseases. Emerging evidence support that melatonin is closely inter-related to other proposed mechanisms contributing to the developmental programming of a variety of chronic NCDs...
February 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28212288/the-search-for-dietary-supplements-to-elevate-or-activate-circulating-paraoxonases
#16
REVIEW
José M Lou-Bonafonte, Clara Gabás-Rivera, María A Navarro, Jesús Osada
Low levels of paraoxonase 1 (PON1) have been associated with the development of several pathological conditions, whereas high levels have been shown to be anti-atherosclerotic in mouse models. These findings suggest that PON1 could be a good surrogate biomarker. The other members of the family, namely PON2 and PON3, the role of which has been much less studied, deserve more attention. This paper provides a systematic review of current evidence concerning dietary supplements in that regard. Preliminary studies indicate that the response to dietary supplements may have a nutrigenetic aspect that will need to be considered in large population studies or in clinical trials...
February 15, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28212278/the-effect-of-the-human-peptide-ghk-on-gene-expression-relevant-to-nervous-system-function-and-cognitive-decline
#17
Loren Pickart, Jessica Michelle Vasquez-Soltero, Anna Margolina
Neurodegeneration, the progressive death of neurons, loss of brain function, and cognitive decline is an increasing problem for senior populations. Its causes are poorly understood and therapies are largely ineffective. Neurons, with high energy and oxygen requirements, are especially vulnerable to detrimental factors, including age-related dysregulation of biochemical pathways caused by altered expression of multiple genes. GHK (glycyl-l-histidyl-l-lysine) is a human copper-binding peptide with biological actions that appear to counter aging-associated diseases and conditions...
February 15, 2017: Brain Sciences
https://www.readbyqxmd.com/read/28212276/preventive-effects-of-pentoxifylline-on-the-development-of-colonic-premalignant-lesions-in-obese-and-diabetic-mice
#18
Kazufumi Fukuta, Yohei Shirakami, Akinori Maruta, Koki Obara, Soichi Iritani, Nobuhiko Nakamura, Takahiro Kochi, Masaya Kubota, Hiroyasu Sakai, Takuji Tanaka, Masahito Shimizu
Obesity and its related metabolic abnormalities, including enhanced oxidative stress and chronic inflammation, are closely related to colorectal tumorigenesis. Pentoxifylline (PTX), a methylxanthine derivative, has been reported to suppress the production of tumor necrosis factor (TNF)-α and possess anti-inflammatory properties. The present study investigated the effects of PTX on the development of carcinogen-induced colorectal premalignant lesions in obese and diabetic mice. Male C57BL/KsJ-db/db mice, which are severely obese and diabetic, were administered weekly subcutaneous injections of the colonic carcinogen azoxymethane (15 mg/kg body weight) for four weeks and then received drinking water containing 125 or 500 ppm PTX for eight weeks...
February 15, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28212273/oxidative-stress-in-copd-sources-markers-and-potential-mechanisms
#19
REVIEW
Adam John Anthony McGuinness, Elizabeth Sapey
Markers of oxidative stress are increased in chronic obstructive pulmonary disease (COPD) and reactive oxygen species (ROS) are able to alter biological molecules, signaling pathways and antioxidant molecule function, many of which have been implicated in the pathogenesis of COPD. However, the involvement of ROS in the development and progression of COPD is not proven. Here, we discuss the sources of ROS, and the defences that have evolved to protect against their harmful effects. We address the role that ROS may have in the development and progression of COPD, as well as current therapeutic attempts at limiting the damage they cause...
February 15, 2017: Journal of Clinical Medicine
https://www.readbyqxmd.com/read/28212205/spontaneous-breathing-during-extracorporeal-membrane-oxygenation-in-acute-respiratory-failure
#20
Stefania Crotti, Nicola Bottino, Giulia Maria Ruggeri, Elena Spinelli, Daniela Tubiolo, Alfredo Lissoni, Alessandro Protti, Luciano Gattinoni
BACKGROUND: We evaluate the clinical feasibility of spontaneous breathing on extracorporeal membrane oxygenation and the interactions between artificial and native lungs in patients bridged to lung transplant or with acute exacerbation of chronic obstructive pulmonary disease (COPD) or acute respiratory distress syndrome. METHODS: The clinical course of a total of 48 patients was analyzed. Twenty-three of 48 patients were enrolled in the prospective study (nine bridged to lung transplant, six COPD, and eight acute respiratory distress syndrome)...
February 17, 2017: Anesthesiology
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