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Daniel Millard, Qianyu Dang, Hong Shi, Xiaou Zhang, Chris Strock, Udo Kraushaar, Haoyu Zeng, Paul Levesque, Hua-Rong Lu, Jean-Michel Guillon, Joseph C Wu, Yingxin Li, Greg Luerman, Blake Anson, Liang Guo, Mike Clements, Yama A Abassi, James Ross, Jennifer Pierson, Gary Gintant
Recent in vitro cardiac safety studies demonstrate the ability of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) to detect electrophysiologic effects of drugs. However, variability contributed by unique approaches, procedures, cell lines and reagents across laboratories makes comparisons of results difficult, leading to uncertainty about the role of hiPSC-CMs in defining proarrhythmic risk in drug discovery and regulatory submissions. A blinded pilot study was conducted to evaluate the electrophysiologic effects of eight well-characterized drugs on four cardiomyocyte lines using a standardized protocol across three microelectrode array (MEA) platforms (18 individual studies)...
April 27, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
Carin Sjöström, Andreas Thorstenson, Viveka Ströck, Abolfazl Hosseini-Aliabad, Firas Aljabery, Fredrik Liedberg, Amir Sherif, Per-Uno Malmström, Johan Rosell, Truls Gårdmark, Staffan Jahnson
OBJECTIVE: The aim of this investigation was to study differences between male and female patients with stage T1 urinary bladder cancer (UBC) regarding intravesical instillation therapy, second resection and survival. MATERIALS AND METHODS: This study included all patients with non-metastatic primary T1 UBC reported to the Swedish National Register of Urinary Bladder Cancer (SNRUBC) from 1997 to 2014, excluding those treated with primary cystectomy. Differences between groups were evaluated using chi-squared tests and logistic regression, and survival was investigated using Kaplan-Meier and log-rank tests and Cox proportional hazards analysis...
April 20, 2018: Scandinavian Journal of Urology
Jenifer A Bradley, Harry H Luithardt, Monica R Metea, Christopher J Strock
Drug-induced seizure liabilities produce significant compound attrition during drug discovery. Currently available in vitro cytotoxicity assays cannot predict all toxicity mechanisms due to the failure of these assays to predict sublethal target-specific electrophysiological liabilities. Identification of seizurogenic and other electrophysiological effects at early stages of the drug development process is important to ensure that safe candidate compounds can be developed while chemical design is taking place, long before these liabilities are discovered in costly preclinical in vivo studies...
May 1, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
Stephen B Strock, Jonathan K Alder, Daniel J Kass
Patients with idiopathic pulmonary fibrosis have a significantly increased risk for the development of lung cancer. The morbidity and mortality of this disease combination are substantial, and, unfortunately, there are currently few data to help guide clinicians in its diagnosis and treatment. In a recent issue of this journal, Hwang et al presented one of the first studies to evaluate lung cancer in patients with idiopathic pulmonary fibrosis at the molecular level. They demonstrate variants in regulators of the cell cycle, which are known to be important in malignant transformation and may also be important in the pathogenesis of idiopathic pulmonary fibrosis...
April 2018: Journal of Pathology
Christopher F Strock, Laurie Morrow de la Riva, Jonathan P Lynch
We tested the hypothesis that reduced root secondary growth of dicotyledonous species improves phosphorus acquisition. Functional-structural modeling in SimRoot indicates that, in common bean ( Phaseolus vulgaris ), reduced root secondary growth reduces root metabolic costs, increases root length, improves phosphorus capture, and increases shoot biomass in low-phosphorus soil. Observations from the field and greenhouse confirm that, under phosphorus stress, resource allocation is shifted from secondary to primary root growth, genetic variation exists for this response, and reduced secondary growth improves phosphorus capture from low-phosphorus soil...
January 2018: Plant Physiology
Yun Hua, Daniel P Camarco, Christopher J Strock, Paul A Johnston
Transcriptional Intermediary Factor 2 (TIF2) is a key Androgen receptor (AR) coactivator that has been implicated in the development and progression of castration resistant prostate cancer (CRPC). This chapter describes the implementation of an AR-TIF2 protein-protein interaction (PPI) biosensor assay to screen for small molecules that can induce AR-TIF2 PPIs, inhibit the DHT-induced formation of AR-TIF2 PPIs, or disrupt pre-existing AR-TIF2 PPIs. The biosensor assay employs high content imaging and analysis to quantify AR-TIF2 PPIs and integrates physiologically relevant cell-based assays with the specificity of binding assays by incorporating structural information from AR and TIF2 functional domains along with intracellular targeting sequences using fluorescent protein reporters...
2018: Methods in Molecular Biology
Christel Häggström, Fredrik Liedberg, Oskar Hagberg, Firas Aljabery, Viveka Ströck, Abolfazl Hosseini, Truls Gårdmark, Amir Sherif, Per-Uno Malmström, Hans Garmo, Staffan Jahnson, Lars Holmberg
PURPOSE: To monitor the quality of bladder cancer care, the Swedish National Register of Urinary Bladder Cancer (SNRUBC) was initiated in 1997. During 2015, in order to study trends in incidence, effects of treatment and survival of men and women with bladder cancer, we linked the SNRUBC to other national healthcare and demographic registers and constructed the Bladder Cancer Data Base Sweden (BladderBaSe). PARTICIPANTS: The SNRUBC is a nationwide register with detailed information on 97% of bladder cancer cases in Sweden as compared with the Swedish Cancer Register...
September 27, 2017: BMJ Open
Georg Jancke, Fredrik Liedberg, Firas Aljabery, Amir Sherif, Viveka Ströck, Per-Uno Malmström, Abolfazl Hosseini-Aliabad, Staffan Jahnson
OBJECTIVE: The aim of this study was to evaluate the use of intravesical treatment and cancer-specific survival of patients with primary carcinoma in situ (CIS). MATERIALS AND METHODS: Data acquisition was based on the Swedish National Registry of Urinary Bladder Cancer by selecting all patients with primary CIS. The analysis covered gender, age, hospital type and hospital volume. Intravesical treatment and death due to bladder cancer were evaluated by multivariate logistic regression and multivariate Cox analysis, respectively...
March 29, 2017: Scandinavian Journal of Urology
Richard M Bergenstal, Ellie Strock, Roger Mazze, Margaret A Powers, Arlene M Monk, Sara Richter, Elisabeth Souhami, Bo Ahrén
BACKGROUND: In the parent study of this analysis, patients with type 2 diabetes received lixisenatide before breakfast or the main meal of the day. This substudy was designed to examine the effect of lixisenatide administered before breakfast or the main meal of the day on continuously assessed 24-hour patient glucose profiles. METHODS: A subset of patients from the parent study underwent 2 14-day periods of continuous glucose monitoring (CGM) at the start and end of the 24-week study...
May 2017: Diabetes/metabolism Research and Reviews
Kimberly Lapham, Jonathan Novak, Lisa D Marroquin, Rachel Swiss, Shuzhen Qin, Christopher J Strock, Renato Scialis, Michael D Aleo, Thomas Schroeter, Heather Eng, A David Rodrigues, Amit S Kalgutkar
Conjugated hyperbilirubinemia accompanied by cholestasis is a frequent side effect during chronic treatment with the antimicrobial agent fusidic acid. Previous studies from our laboratory, addressing mechanisms of musculoskeletal toxicity arising from coadministration of fusidic acid with statins, demonstrated the ability of fusidic acid to potently inhibit human organic anion transporting polypeptides OATP1B1 (IC50 = 1.6 μM) and OATP1B3 (IC50 = 2.5 μM), which are responsible for the uptake-limited clearance of statins as well as bilirubin glucuronide conjugates...
October 4, 2016: Chemical Research in Toxicology
Ashley T Fancher, Yun Hua, Daniel P Camarco, David A Close, Christopher J Strock, Paul A Johnston
The continued activation of androgen receptor (AR) transcription and elevated expression of AR and transcriptional intermediary factor 2 (TIF2) coactivator observed in prostate cancer (CaP) recurrence and the development of castration-resistant CaP (CRPC) support a screening strategy for small-molecule inhibitors of AR-TIF2 protein-protein interactions (PPIs) to find new drug candidates. Small molecules can elicit tissue selective effects, because the cells of distinct tissues express different levels and cohorts of coregulatory proteins...
October 2016: Assay and Drug Development Technologies
Daniel C Millard, Christopher J Strock, Coby B Carlson, Natsuyo Aoyama, Krisztina Juhasz, Tom A Goetze, Sonja Stoelzle-Feix, Nadine Becker, Niels Fertig, Craig T January, Blake D Anson, James D Ross
Drug-drug interactions pose a difficult drug safety problem, given the increasing number of individuals taking multiple medications and the relative complexity of assessing the potential for interactions. For example, sofosbuvir-based drug treatments have significantly advanced care for hepatitis C virus-infected patients, yet recent reports suggest interactions with amiodarone may cause severe symptomatic bradycardia and thus limit an otherwise extremely effective treatment. Here, we evaluated the ability of human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) to recapitulate the interaction between sofosbuvir and amiodarone in vitro, and more generally assessed the feasibility of hiPSC-CMs as a model system for drug-drug interactions...
November 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
Aysegül Ilhan-Mutlu, Matthias Osswald, Yunxiang Liao, Miriam Gömmel, Martin Reck, David Miles, Paola Mariani, Luca Gianni, Beatrix Lutiger, Viktor Nendel, Stefanie Srock, Pablo Perez-Moreno, Frits Thorsen, Louisa von Baumgarten, Matthias Preusser, Wolfgang Wick, Frank Winkler
Patients with nonsquamous non-small cell lung cancer (nsNSCLC; largely lung adenocarcinoma) are at high risk of developing brain metastases. Preclinical data suggested that anti-VEGF-A therapy may prevent the formation of nsNSCLC brain metastases. Whether non-brain metastases are also prevented, and whether bevacizumab shows a brain metastases-preventive activity in cancer patients is unknown. Data of one nsNSCLC (stage IIIB/IV, AVAiL) and two breast cancer bevacizumab trials (HER2 negative, AVADO; HER2 positive, AVEREL) were retrospectively analyzed regarding the frequency of the brain versus other organs being the site of first relapse...
April 2016: Molecular Cancer Therapeutics
Louis L Strock
The transaxillary approach to breast augmentation has the advantage of allowing breast implants to be placed with no incisions on the breasts. There has been a general perception of a lack of technical control compared with the inframammary approach. This article presents the transaxillary approach from the perspective of the technical control gained with the aid of an endoscope, which allows precise creation of the tissue pocket with optimal visualization. The aspects of technique that allow optimal technical control are discussed, in addition to postoperative processes that aid in stabilizing the device position and allow consistent and predictable outcomes...
October 2015: Clinics in Plastic Surgery
Stephen B Strock, Wendi Mason, James E Loyd
No abstract text is available yet for this article.
September 15, 2015: American Journal of Respiratory and Critical Care Medicine
Carrie F Olson-Manning, Christopher F Strock, Thomas Mitchell-Olds
The connections leading from genotype to fitness are not well understood, yet they are crucial for a diverse set of disciplines. Uncovering the general properties of biochemical pathways that influence ecologically important traits is an effective way to understand these connections. Enzyme flux control (or, control over pathway output) is one such pathway property. The flux-controlling enzyme in the antiherbivory aliphatic glucosinolate pathway of Arabidopsis thaliana has majority flux control under benign greenhouse conditions and has evidence of nonneutral evolution...
September 10, 2015: G3: Genes—Genomes—Genetics
Louis L Strock
No abstract text is available yet for this article.
November 2015: Aesthetic Surgery Journal
Stephen B Strock, Silvana Gaudieri, Simon Mallal, Chang Yu, Daphne Mitchell, Joy Cogan, Wendi Mason, Deborah Crowe, James E Loyd
BACKGROUND: Fibrosing mediastinitis (FM) is an idiosyncratic reaction to infection with Histoplasma capsulatum with a prevalence of 3:100,000 people infected. The rarity of post-histoplasmosis fibrosing mediastinitis (PHFM) in areas where H. capsulatum is endemic suggests that an abnormal immunological host response may be responsible for the development of fibrosis. Our group previously reported an association between subjects with PHFM and human leukocyte antigen (HLA)-A*02. We sought to confirm or extend those findings with application of high resolution HLA typing in a cohort of subjects with PHFM...
2015: BMC Infectious Diseases
Yun Hua, Christopher J Strock, Paul A Johnston
This chapter describes the implementation of the p53-hDM2 protein-protein interaction (PPI) biosensor (PPIB) HCS assay to identify disruptors of p53-hDM2 PPIs. Recombinant adenovirus expression constructs were generated bearing the individual p53-GFP and hDM2-RFP PPI partners. The N-terminal p53 transactivating domain that contains the binding site for hDM2 is expressed as a GFP fusion protein that is targeted and anchored in the nucleolus of infected cells by a nuclear localization (NLS) sequence. The p53-GFP biosensor is localized to the nucleolus to enhance and facilitate the image acquisition and analysis of the PPIs...
2015: Methods in Molecular Biology
Amy P Myers, Troy A Watson, Steven B Strock
The likelihood of a drug reaction with lamotrigine is increased by dose escalation that is too rapid or drug interactions that increase the concentration of lamotrigine. There is a well-documented interaction between valproic acid and lamotrigine in which lamotrigine levels are increased, subsequently increasing the risk of a drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome. This syndrome is characterized by fever, lymphadenopathy, diffuse maculopapular rash, multivisceral involvement, eosinophilia, and atypical lymphocytes and has a mortality rate of 10-40%...
March 2015: Pharmacotherapy
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