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Sinead Toomey, Stephen F Madden, Simon J Furney, Yue Fan, Mark McCormack, Carragh Stapleton, Mattia Cremona, Gianpiero L Cavalleri, Malgorzata Milewska, Naomi Elster, Aoife Carr, Joanna Fay, Elaine W Kay, Susan Kennedy, John Crown, William M Gallagher, Bryan T Hennessy, Alex J Eustace
BACKGROUND: Trastuzumab treatment for women with HER2-positive breast cancer (BC) resulted in the significant improvement of both relapse free survival (RFS) and overall survival (OS). However, many women who are classified as HER2-positive do not respond. Many studies have focused on the role of somatic mutations rather than germline polymorphisms in trastuzumab resistance. RESULTS: We completed an Agena MassArray screen of 10 ERBB-family single nucleotide polymorphisms (SNPs) in 194 adjuvant trastuzumab treated HER2-positive BC patients...
October 20, 2016: Oncotarget
Gráinne S Gorman, Patrick F Chinnery, Salvatore DiMauro, Michio Hirano, Yasutoshi Koga, Robert McFarland, Anu Suomalainen, David R Thorburn, Massimo Zeviani, Douglass M Turnbull
Mitochondrial diseases are a group of genetic disorders that are characterized by defects in oxidative phosphorylation and caused by mutations in genes in the nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) that encode structural mitochondrial proteins or proteins involved in mitochondrial function. Mitochondrial diseases are the most common group of inherited metabolic disorders and are among the most common forms of inherited neurological disorders. One of the challenges of mitochondrial diseases is the marked clinical variation seen in patients, which can delay diagnosis...
October 20, 2016: Nature Reviews. Disease Primers
Philip Egan, Stephen Drain, Caroline Conway, Anthony J Bjourson, H Denis Alexander
Plasma cell myeloma is a clinically heterogeneous malignancy accounting for approximately one to 2% of newly diagnosed cases of cancer worldwide. Treatment options, in addition to long-established cytotoxic drugs, include autologous stem cell transplant, immune modulators, proteasome inhibitors and monoclonal antibodies, plus further targeted therapies currently in clinical trials. Whilst treatment decisions are mostly based on a patient's age, fitness, including the presence of co-morbidities, and tumour burden, significant scope exists for better risk stratification, sub-classification of disease, and predictors of response to specific therapies...
October 21, 2016: International Journal of Molecular Sciences
B N Keel, J W Keele, W M Snelling
Copy number variations (CNVs) are large insertions, deletions or duplications in the genome that vary between members of a species and are known to affect a wide variety of phenotypic traits. In this study, we identified CNVs in a population of bulls using low coverage next-generation sequence data. First, in order to determine a suitable strategy for CNV detection in our data, we compared the performance of three distinct CNV detection algorithms on benchmark CNV datasets and concluded that using the multiple sample read depth approach was the best method for identifying CNVs in our sequences...
October 24, 2016: Animal Genetics
Aldo Isaac Martínez-Banderas, Antonio Aires, Francisco J Teran, Jose Efrain Perez, Jael F Cadenas, Nouf Alsharif, Timothy Ravasi, Aitziber L Cortajarena, Jürgen Kosel
Exploiting and combining different properties of nanomaterials is considered a potential route for next generation cancer therapies. Magnetic nanowires (NWs) have shown good biocompatibility and a high level of cellular internalization. We induced cancer cell death by combining the chemotherapeutic effect of doxorubicin (DOX)-functionalized iron NWs with the mechanical disturbance under a low frequency alternating magnetic field. (3-aminopropyl)triethoxysilane (APTES) and bovine serum albumin (BSA) were separately used for coating NWs allowing further functionalization with DOX...
October 24, 2016: Scientific Reports
Hongming Lyu, Qi Lu, Jinbiao Liu, Xiaoming Wu, Jinyu Zhang, Junfeng Li, Jiebin Niu, Zhiping Yu, Huaqiang Wu, He Qian
In order to conquer the short-channel effects that limit conventional ultra-scale semiconductor devices, two-dimensional materials, as an option of ultimate thin channels, receive wide attention. Graphene, in particular, bears great expectations because of its supreme carrier mobility and saturation velocity. However, its main disadvantage, the lack of bandgap, has not been satisfactorily solved. As a result, maximum oscillation frequency (fmax) which indicates transistors' power amplification ability has been disappointing...
October 24, 2016: Scientific Reports
Han Xia, Andrew S Beck, Aysen Gargili, Naomi Forrester, Alan D T Barrett, Dennis A Bente
The trade-off hypothesis, the current paradigm of arbovirus evolution, proposes that cycling between vertebrate and invertebrate hosts presents significant constraints on genetic change of arboviruses. Studying these constraints in mosquito-borne viruses has led to a new understanding of epizootics. The trade-off hypothesis is assumed to be applicable to tick-borne viruses too, although studies are lacking. Tick-borne Crimean-Congo hemorrhagic fever virus (CCHFV), a member of the family Bunyaviridae, is a major cause of severe human disease worldwide and shows an extraordinary amount of genetic diversity compared to other arboviruses, which has been linked to increased virulence and emergence in new environments...
October 24, 2016: Scientific Reports
Ya-Li Liu, Dong-Fang Li, He-Ping Xu, Meng Xiao, Jing-Wei Cheng, Li Zhang, Zhi-Peng Xu, Xin-Xin Chen, Ge Zhang, Timothy Kudinha, Fanrong Kong, Yan-Ping Gong, Xin-Ying Wang, Yin-Xin Zhang, Hong-Long Wu, Ying-Chun Xu
Although previous studies have confirmed that 23S rRNA gene mutation could be responsible for most of macrolide resistance in M. catarrhalis, a recent study suggested otherwise. Next generation sequence based comparative genomics has revolutionized the mining of potential novel drug resistant mechanisms. In this study, two pairs of resistant and susceptible M. catarrhalis isolates with different multilocus sequence types, were investigated for potential differential genes or informative single nucleotide polymorphisms (SNPs)...
October 24, 2016: Scientific Reports
Kenji Amemiya, Yosuke Hirotsu, Taichiro Goto, Hiroshi Nakagomi, Hitoshi Mochizuki, Toshio Oyama, Masao Omata
Identifying genetic alterations in tumors is critical for molecular targeting of therapy. In the clinical setting, formalin-fixed paraffin-embedded (FFPE) tissue is usually employed for genetic analysis. However, DNA extracted from FFPE tissue is often not suitable for analysis because of its low levels and poor quality. Additionally, FFPE sample preparation is time-consuming. To provide early treatment for cancer patients, a more rapid and robust method is required for precision medicine. We present a simple method for genetic analysis, called touch imprint cytology combined with massively paralleled sequencing (touch imprint cytology [TIC]-seq), to detect somatic mutations in tumors...
October 24, 2016: Cancer Medicine
Jie Wang, Haijing Shen, Xiaoxia Hu, Yan Li, Zhihao Li, Jinfan Xu, Xiufeng Song, Haibo Zeng, Quan Yuan
For the water remediation techniques based on adsorption, the long-standing contradictories between selectivity and multiple adsorbability, as well as between affinity and recyclability, have put it on weak defense amid more and more severe environment crisis. Here, a pollutant-targeting hydrogel scavenger is reported for water remediation with both high selectivity and multiple adsorbability for several pollutants, and with strong affinity and good recyclability through rationally integrating the advantages of multiple functional materials...
March 2016: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
Fleur M Ferguson, Jing Ni, Tinghu Zhang, Bethany Tesar, Taebo Sim, Nam Doo Kim, Xianming Deng, Jennifer R Brown, Jean J Zhao, Nathanael S Gray
Dual inhibition of PI3K-δ and PI3K-γ is an established therapeutic strategy for treatment of hematological malignancies. Reported molecules targeting PI3K-δ/γ selectively are chemically similar and based upon isoquinolin-1(2H)-one or quinazolin-4(3H)-one scaffolds. Here we report a chemically distinct series of potent, selective PI3K-δ/γ inhibitors based on a 5,11-dihydro-6H-benzo[e]pyrimido[5,4-b][1,4]diazepin-6-one scaffold with comparable biochemical potency and cellular effects on PI3K signaling. We envisage these molecules will provide useful leads for development of next-generation PI3K-δ/γ targeting therapeutics...
October 13, 2016: ACS Medicinal Chemistry Letters
Nevena Mihailovic-Stanojevic, Zoran Miloradović, Milan Ivanov, Branko Bugarski, Đurđica Jovović, Danijela Karanović, Una-Jovana Vajić, Draženka Komes, Jelica Grujić-Milanović
High blood pressure is the most powerful contributor to the cardiovascular morbidity and mortality, and inverse correlation between consumption of polyphenol-rich foods or beverages and incidence of cardiovascular diseases gains more importance. Reactive oxygen species plays an important role in the development of hypertension. We found that wild thyme (a spice plant, rich in polyphenolic compounds) induced a significant decrease of blood pressure and vascular resistance in hypertensive rats. The inverse correlation between vascular resistance and plasma heme oxygenase-1 suggests that endogenous vasodilator carbon monoxide generated by heme oxidation could account for this normalization of blood pressure...
2016: Oxidative Medicine and Cellular Longevity
Nicola J Stagg, Ben-Quan Shen, Flavia Brunstein, Chunze Li, Amrita V Kamath, Fiona Zhong, Melissa Schutten, Bernard M Fine
Antibody drug conjugates (ADC) consist of potent cytotoxic drugs conjugated to antibodies via chemical linkers, which enables specific targeting of tumor cells while reducing systemic exposure to the cytotoxic drug and improving the therapeutic window. The valine citrulline monomethyl auristatin E (vcMMAE, conventional linker-drug) ADC platform has shown promising clinical activity in several cancers, but peripheral neuropathy (PN) is a frequent adverse event leading to treatment discontinuation and dose reduction...
October 20, 2016: Regulatory Toxicology and Pharmacology: RTP
Mirette M Saad, Mioara Gavrilla, Keith Byron, David Deam
No abstract text is available yet for this article.
February 2016: Pathology
Tudor Groza
No abstract text is available yet for this article.
February 2016: Pathology
W A Cooper, S Kraitsek, C I Selinger, T Tran, M Kohonen-Corish, S A O'Toole, B Yu
No abstract text is available yet for this article.
February 2016: Pathology
Shuai Xu, James Allred, Brandon Kirsch, Adam Raff, R Rox Anderson, William Ju
No abstract text is available yet for this article.
November 2016: Journal of Investigative Dermatology
T Gosiewski, A H Ludwig-Galezowska, K Huminska, A Sroka-Oleksiak, P Radkowski, D Salamon, J Wojciechowicz, M Kus-Slowinska, M Bulanda, P P Wolkow
Blood is considered to be a sterile microenvironment, in which bacteria appear only periodically. Previously used methods allowed only for the detection of either viable bacteria with low sensitivity or selected species of bacteria. The Next-Generation Sequencing method (NGS) enables the identification of all bacteria in the sample with their taxonomic classification. We used NGS for the analysis of blood samples from healthy volunteers (n = 23) and patients with sepsis (n = 62) to check whether any bacterial DNA exists in the blood of healthy people and to identify bacterial taxonomic profile in the blood of septic patients...
October 22, 2016: European Journal of Clinical Microbiology & Infectious Diseases
R Gaillard, S Lustig, A Peltier, V Villa, E Servien, P Neyret
BACKGROUND: Despite excellent long-term outcomes, posterior stabilisation by a third condyle continues to receive unwarranted criticism regarding patellar complications and instability. HYPOTHESIS: Complication rates with a tri-condylar posterior-stabilised implant are similar to those with other posterior-stabilised prostheses and have diminished over time due to improvements in prosthesis design. MATERIAL AND METHODS: Post-operative complications and revision rates were assessed retrospectively in a prospective cohort of 4189 consecutive patients who had primary total knee arthroplasty (TKA) using a tri-condylar posterior-stabilised implant (Wright-Tornier) and were then followed-up for at least 24 months...
October 19, 2016: Orthopaedics & Traumatology, Surgery & Research: OTSR
Samah Nassereddine, Taiga Nishihori, Eric Padron, Rami Mahfouz, Ali Bazarbachi, Rami S Komrokji, Mohamed A Kharfan-Dabaja
Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal hematopoietic neoplastic disorders most commonly occurring in the elderly population; MDS has a tendency to progress to acute leukemia. Although epigenetic therapies have improved the outcomes of MDS patients, allogeneic hematopoietic cell transplantation remains the only curative option. Molecular characterization of MDS using next-generation sequencing has expanded not only the knowledge on MDS but also the depth of understanding of evolution and contribution of recurrent somatic mutations in precursor conditions...
September 16, 2016: Clinical Lymphoma, Myeloma & Leukemia
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