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https://www.readbyqxmd.com/read/27923043/clonal-evolutionary-analysis-during-her2-blockade-in-her2-positive-inflammatory-breast-cancer-a-phase-ii-open-label-clinical-trial-of-afatinib-vinorelbine
#1
Gerald Goh, Ramona Schmid, Kelly Guiver, Wichit Arpornwirat, Imjai Chitapanarux, Vinod Ganju, Seock-Ah Im, Sung-Bae Kim, Arunee Dechaphunkul, Jedzada Maneechavakajorn, Neil Spector, Thomas Yau, Mehdi Afrit, Slim Ben Ahmed, Stephen R Johnston, Neil Gibson, Martina Uttenreuther-Fischer, Javier Herrero, Charles Swanton
BACKGROUND: Inflammatory breast cancer (IBC) is a rare, aggressive form of breast cancer associated with HER2 amplification, with high risk of metastasis and an estimated median survival of 2.9 y. We performed an open-label, single-arm phase II clinical trial (ClinicalTrials.gov NCT01325428) to investigate the efficacy and safety of afatinib, an irreversible ErbB family inhibitor, alone and in combination with vinorelbine in patients with HER2-positive IBC. This trial included prospectively planned exome analysis before and after afatinib monotherapy...
December 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27922988/minimally-invasive-fundoplication-is-safe-and-effective-in-patients-with-severe-esophageal-hypomotility
#2
Michael B Goldberg, Abbas El-Sayed Abbas, Michael S Smith, Henry P Parkman, Ron Schey, Daniel T Dempsey
OBJECTIVE: Fundoplication is used to treat refractory gastroesophageal reflux disease (GERD). A subset of patients has coexisting esophageal dysmotility, including aperistalsis or hypoperistalsis. These patients may be at increased risk of dysphagia after fundoplication. To evaluate the outcomes of minimally invasive fundoplication (MIF) in patients with GERD and esophageal hypomotility. METHODS: Retrospective review of all patients who underwent MIF and had severe esophageal hypomotility from January 2003 to June 2013...
December 5, 2016: Innovations: Technology and Techniques in Cardiothoracic and Vascular Surgery
https://www.readbyqxmd.com/read/27922820/rapamycin-treatment-benefits-glucose-metabolism-in-mouse-models-of-type-2-diabetes
#3
Peter C Reifsnyder, Kevin Flurkey, Austen Te, David E Harrison
Numerous studies suggest that rapamycin treatment promotes insulin resistance, implying that rapamycin could have negative effects on patients with, or at risk for, type 2 diabetes (T2D). New evidence, however, indicates that rapamycin treatment produces some benefits to energy metabolism, even in the context of T2D. Here, we survey 5 mouse models of T2D (KK, KK-Ay, NONcNZO10, BKS-db/db, TALLYHO) to quantify effects of rapamycin on well-recognized markers of glucose homeostasis within a wide range of T2D environments...
November 30, 2016: Aging
https://www.readbyqxmd.com/read/27922752/abnormal-glucose-metabolism-and-high-energy-expenditure-in-idiopathic-pulmonary-arterial-hypertension
#4
Gustavo A Heresi, Steven K Malin, Jarrod W Barnes, Liping Tian, John P Kirwan, Raed A Dweik
RATIONALE: Insulin resistance has emerged as a potential mechanism related to the pathogenesis of idiopathic pulmonary arterial hypertension (IPAH). However, direct measurements of insulin and glucose metabolism have not been performed in IPAH patients to date. OBJECTIVES: To perform comprehensive metabolic phenotyping on humans with IPAH. METHODS: We assessed plasma insulin and glucose using an oral glucose tolerance test and estimated insulin resistance and beta-cell function in 14 IPAH patients and 14 controls matched for age, sex, blood pressure, and body mass index (BMI),...
December 6, 2016: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/27922722/topiramate-versus-carbamazepine-monotherapy-for-epilepsy-an-individual-participant-data-review
#5
REVIEW
Sarah J Nolan, Maria Sudell, Catrin Tudur Smith, Anthony G Marson
BACKGROUND: Epilepsy is a common neurological condition in which abnormal electrical discharges from the brain cause recurrent unprovoked seizures. It is believed that with effective drug treatment, up to 70% of individuals with active epilepsy have the potential to become seizure-free and go into long-term remission shortly after starting drug therapy, the majority of which may be able to achieve remission with a single antiepileptic drug (AED).The correct choice of first-line antiepileptic therapy for individuals with newly diagnosed seizures is of great importance...
December 6, 2016: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/27922601/the-effect-of-extrinsic-mortality-on-genome-size-evolution-in-prokaryotes
#6
Piotr Bentkowski, Cock van Oosterhout, Ben Ashby, Thomas Mock
Mortality has a significant role in prokaryotic ecology and evolution, yet the impact of variations in extrinsic mortality on prokaryotic genome evolution has received little attention. We used both mathematical and agent-based models to reveal how variations in extrinsic mortality affect prokaryotic genome evolution. Our results suggest that the genome size of bacteria increases with increased mortality. A high extrinsic mortality increases the pool of free resources and shortens life expectancy, which selects for faster reproduction, a phenotype we called 'scramblers'...
December 6, 2016: ISME Journal
https://www.readbyqxmd.com/read/27922071/a-carotenogenic-mini-pathway-introduced-into-white-corn-does-not-affect-development-or-agronomic-performance
#7
Daniela Zanga, Teresa Capell, Gustavo A Slafer, Paul Christou, Roxana Savin
High-carotenoid corn (Carolight®) has been developed as a vehicle to deliver pro-vitamin A in the diet and thus address vitamin A deficiency in at-risk populations in developing countries. Like any other novel crop, the performance of Carolight® must be tested in different environments to ensure that optimal yields and productivity are maintained, particularly in this case to ensure that the engineered metabolic pathway does not attract a yield penalty. Here we compared the performance of Carolight® with its near isogenic white corn inbred parental line under greenhouse and field conditions, and monitored the stability of the introduced trait...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27921320/cardiac-effects-of-amiselimod-compared-with-fingolimod-and-placebo-results-of-a-randomised-parallel-group-phase-i-study-in-healthy-subjects
#8
Tomohiko Harada, Darren Wilbraham, Guillemette de La Borderie, Shinsuke Inoue, Jim Bush, A John Camm
AIM: Amiselimod (MT-1303) is a selective sphingosine 1-phosphate 1 (S1P1 ) receptor modulator which is currently being developed for the treatment of various autoimmune diseases. Unlike some other S1P receptor modulators, amiselimod seemed to show a favourable cardiac safety profile in pre-clinical, phase I and II studies. The aim of this study was to characterise the cardiac effects of amiselimod by directly comparing it with fingolimod and placebo. METHODS: Eighty-one (81) healthy subjects aged 18-55 years were equally randomised to receive amiselimod 0...
December 6, 2016: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/27921276/relationship-between-physician-adjudicated-adverse-events-and-patient-reported-health-related-quality-of-life-in-a-phase-ii-clinical-trial-nct01143402-of-patients-with-metastatic-uveal-melanoma
#9
Thomas M Atkinson, Jennifer L Hay, Alexander Shoushtari, Yuelin Li, Daniel J Paucar, Sloane C Smith, Ragini R Kudchadkar, Austin Doyle, Jeffrey A Sosman, Jorge Fernando Quevedo, Mohammed M Milhem, Anthony M Joshua, Gerald P Linette, Thomas F Gajewski, Jose Lutzky, David H Lawson, Christopher D Lao, Patrick J Flynn, Mark R Albertini, Takami Sato, Karl Lewis, Brian Marr, David H Abramson, Mark Andrew Dickson, Gary K Schwartz, Richard D Carvajal
PURPOSE: Clinical trials commonly use physician-adjudicated adverse event (AE) assessment via the common terminology criteria for adverse events (CTCAE) for decision-making. Patient-reported health-related quality of life (HRQoL) data are becoming more frequent in oncology; however, the relationship between physician-adjudicated AE assessment and HRQoL is understudied. METHODS: Data from a phase II trial (clinicaltrials.gov identifier: NCT01143402) where patients with metastatic uveal melanoma were randomized to receive selumetinib, an oral MEK inhibitor, or chemotherapy were analyzed...
December 5, 2016: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/27921270/halogenated-indoles-eradicate-bacterial-persister-cells-and-biofilms
#10
Jin-Hyung Lee, Yong-Guy Kim, Giyeon Gwon, Thomas K Wood, Jintae Lee
The emergence of antibiotic resistance has necessitated new therapeutic approaches to combat recalcitrant bacterial infections. Persister cells, often found in biofilms, are metabolically dormant, and thus, are highly tolerant to all traditional antibiotics and represent a major drug resistance mechanism. In the present study, 36 diverse indole derivatives were investigated with the aim of identifying novel compounds that inhibit persisters and biofilm formation by Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus...
December 2016: AMB Express
https://www.readbyqxmd.com/read/27921142/intra-population-variability-of-ocean-acidification-impacts-on-the-physiology-of-baltic-blue-mussels-mytilus-edulis-integrating-tissue-and-organism-response
#11
L S Stapp, J Thomsen, H Schade, C Bock, F Melzner, H O Pörtner, G Lannig
Increased maintenance costs at cellular, and consequently organism level, are thought to be involved in shaping the sensitivity of marine calcifiers to ocean acidification (OA). Yet, knowledge of the capacity of marine calcifiers to undergo metabolic adaptation is sparse. In Kiel Fjord, blue mussels thrive despite periodically high seawater PCO2, making this population interesting for studying metabolic adaptation under OA. Consequently, we conducted a multi-generation experiment and compared physiological responses of F1 mussels from 'tolerant' and 'sensitive' families exposed to OA for 1 year...
December 5, 2016: Journal of Comparative Physiology. B, Biochemical, Systemic, and Environmental Physiology
https://www.readbyqxmd.com/read/27920783/genomic-tools-in-pearl-millet-breeding-for-drought-tolerance-status-and-prospects
#12
REVIEW
Desalegn D Serba, Rattan S Yadav
Pearl millet [Penisetum glaucum (L) R. Br.] is a hardy cereal crop grown in the arid and semiarid tropics where other cereals are likely to fail to produce economic yields due to drought and heat stresses. Adaptive evolution, a form of natural selection shaped the crop to grow and yield satisfactorily with limited moisture supply or under periodic water deficits in the soil. Drought tolerance is a complex polygenic trait that various morphological and physiological responses are controlled by 100s of genes and significantly influenced by the environment...
2016: Frontiers in Plant Science
https://www.readbyqxmd.com/read/27920767/ecophysiology-and-comparative-genomics-of-nitrosomonas-mobilis-ms1-isolated-from-autotrophic-nitrifying-granules-of-wastewater-treatment-bioreactor
#13
Soe Myat Thandar, Norisuke Ushiki, Hirotsugu Fujitani, Yuji Sekiguchi, Satoshi Tsuneda
Ammonia-oxidizing bacteria (AOB), which oxidize ammonia to nitrite in the first step of nitrification, play an important role in biological wastewater treatment systems. Nitrosomonas mobilis is an important and dominant AOB in various wastewater treatment systems. However, the detailed physiological and genomic properties of N. mobilis have not been thoroughly investigated because of limited success isolating pure cultures. This study investigated the key physiological characteristics of N. mobilis Ms1, which was previously isolated into pure culture from the nitrifying granules of wastewater treatment bioreactor...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27920766/a-degu-p-and-degq-dependent-regulatory-pathway-for-the-k-state-in-bacillus-subtilis
#14
Mathieu Miras, David Dubnau
The K-state in the model bacterium Bacillus subtilis is associated with transformability (competence) as well as with growth arrest and tolerance for antibiotics. Entry into the K-state is determined by the stochastic activation of the transcription factor ComK and occurs in about ∼15% of the population in domesticated strains. Although the upstream mechanisms that regulate the K-state have been intensively studied and are well understood, it has remained unexplained why undomesticated isolates of B. subtilis are poorly transformable compared to their domesticated counterparts...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27920558/monitoring-the-effects-of-doxorubicin-on-3d-spheroid-tumor-cells-in-real-time
#15
NamHuk Baek, Ok Won Seo, MinSung Kim, John Hulme, Seong Soo A An
Recently, increasing numbers of cell culture experiments with 3D spheroids presented better correlating results in vivo than traditional 2D cell culture systems. 3D spheroids could offer a simple and highly reproducible model that would exhibit many characteristics of natural tissue, such as the production of extracellular matrix. In this paper numerous cell lines were screened and selected depending on their ability to form and maintain a spherical shape. The effects of increasing concentrations of doxorubicin (DXR) on the integrity and viability of the selected spheroids were then measured at regular intervals and in real-time...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27920527/pharmacokinetics-and-safety-of-dts-108-a-human-oligopeptide-bound-to-sn-38-with-an-esterase-sensitive-cross-linker-in-patients-with-advanced-malignancies-a-phase-i-study
#16
Romain Coriat, Sandrine J Faivre, Olivier Mir, Chantal Dreyer, Stanislas Ropert, Mohammed Bouattour, Robert Desjardins, François Goldwasser, Eric Raymond
BACKGROUND: DTS-108 is a hydrosoluble prodrug, where the SN-38 moiety is covalently linked to a 20-amino acid vector peptide by a specific esterase-sensitive cross-linker, releasing 7-ethyl-10-hydroxycampthotecin (SN-38) by esterase bond cleavage. METHODS: The pharmacokinetics of DTS-108, adverse events graded according to NCI-CTCv3.1, dose-limiting toxicities at cycle 1, the maximum tolerated dose (MTD), and the recommended Phase II dose (RP2D) of intravenous DTS-108 (1-2 hours) every 2 weeks were evaluated in a first-in-human Phase I study in patients with advanced/metastatic carcinomas, according to an accelerated dose escalation design...
2016: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/27920498/feasibility-of-sequential-adjuvant-chemotherapy-with-a-3-month-oxaliplatin-based-regimen-followed-by-3-months-of-capecitabine-in-patients-with-stage-iii-and-high-risk-stage-ii-colorectal-cancer-jswog-c2-study
#17
Atsushi Tsuruta, Kazuki Yamashita, Hiroaki Tanioka, Akihito Tsuji, Michio Inukai, Toshiki Yamakawa, Tomoki Yamatsuji, Masanori Yoshimitsu, Kazuhiro Toyota, Taketoshi Yamano, Takeshi Nagasaka, Masazumi Okajima
BACKGROUND: Six months of oxaliplatin-based chemotherapy is the standard adjuvant chemotherapy for completely resected stage III colorectal cancer (CRC). Also, patients with stage II CRC who are considered to be at high risk of disease recurrence often receive the same adjuvant chemotherapy treatment. We prospectively investigated the extent and degree of neuropathy suffered by stage III and high-risk stage II resectable CRC patients who underwent sequential approach involving 3 months of an oxaliplatin-based regimen followed by 3 months of capecitabine...
2016: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/27920482/hepatitis-c-virus-therapy-with-peg-interferon-and-ribavirin-in-myanmar-a-resource-constrained-country
#18
Naomi Khaing Than Hlaing, Debolina Banerjee, Robert Mitrani, Soe Htet Arker, Kyaw San Win, Nyan Lin Tun, Zaw Thant, Khin Maung Win, K Rajender Reddy
AIM: To investigate peg-interferon (peg-IFN) and ribavirin (RBV) therapy in Myanmar and to predict sustained virologic response (SVR). METHODS: This single-center, open-label, study was conducted in Myanmar between 2009 and 2014. A total of 288 patients infected with HCV genotypes 1, 2, 3 and 6 were treated with peg-IFN alpha-2a (180 μg/wk) or alpha-2b (50 to 100 μg as a weight-based dose) and RBV as a weight-based dose (15 mg/kg/d). Treatment duration was 48 wk for genotypes 1 and 6, 24 wk for genotype 2, and 24 or 48 wk for genotype 3 based on rapid virologic response (RVR)...
November 21, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27920389/resistance-in-persisting-bat-populations-after-white-nose-syndrome-invasion
#19
Kate E Langwig, Joseph R Hoyt, Katy L Parise, Winifred F Frick, Jeffrey T Foster, A Marm Kilpatrick
Increases in anthropogenic movement have led to a rise in pathogen introductions and the emergence of infectious diseases in naive host communities worldwide. We combined empirical data and mathematical models to examine changes in disease dynamics in little brown bat (Myotis lucifugus) populations following the introduction of the emerging fungal pathogen Pseudogymnoascus destructans, which causes the disease white-nose syndrome. We found that infection intensity was much lower in persisting populations than in declining populations where the fungus has recently invaded...
January 19, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/27920091/interferon-gamma-limits-diabetogenic-cd8-t-cell-effector-responses-in-type-1-diabetes
#20
John P Driver, Jeremy J Racine, Cheng Ye, Deanna J Lamont, Brittney N Newby, Caroline G McPhee-Leeth, Harold D Chapman, Todd M Brusko, Yi-Guang Chen, Clayton E Mathews, David V Serreze
Type 1 diabetes development in the NOD mouse model is widely reported to be dependent on high-level production by autoreactive CD4(+) and CD8(+) T-cells of IFNγ, generally considered a pro-inflammatory cytokine. However, IFNγ can also participate in tolerance induction pathways, indicating it is not solely pro-inflammatory. This study addresses how IFNγ can suppress activation of diabetogenic CD8(+) T-cells. CD8(+) T-cells transgenically expressing the diabetogenic AI4 T-cell receptor (TCR) adoptively transferred disease to otherwise unmanipulated NOD...
December 5, 2016: Diabetes
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