Comparative effects of SNX-7081 and SNX-2112 on cell cycle, apoptosis and Hsp90 client proteins in human cancer cells.

SNX-2112, a novel 2-aminobenzamide inhibitor of Hsp90, previously showed a broad spectrum of anticancer activity. However, subsequent development has been discontinued due to ocular toxicity as identified in a phase I study. SNX-7081, another closely related Hsp90 inhibitor with a side chain of indole instead of indazole, has recently attracted attention.

Combination of SNX-2112 with 5-FU exhibits antagonistic effect in esophageal cancer cells.

The low efficacy of single-drug chemotherapy forms the basis for combination therapy in esophageal squamous cell carcinoma. SNX-2112, a selective heat shock protein 90 (Hsp90) inhibitor, was recently reported as being effective in combination with cisplatin and paclitaxel. In this study, we investigated the effect of SNX-2112 in combination with 5-fluorouracil (5-FU), another first-line anticancer drug, in esophageal cancer.

Parental awareness and use of online physician rating sites.

Background And Objective: The US public is increasingly using online rating sites to make decisions about a variety of consumer goods and services, including physicians. We sought to understand, within the context of other types of rating sites, parents' awareness, perceptions, and use of physician-rating sites for choosing primary care physicians for their children.

Methods: This cross-sectional, nationally representative survey of 3563 adults was conducted in September 2012.

Ultrasonic elasticity determination of 45S5 Bioglass(®)-based scaffolds: influence of polymer coating and crosslinking treatment.

Highly porous 45S5 Bioglass(®)-based scaffolds with interconnected pore structure are promising candidates for bone tissue engineering due to their bioactivity, biocompatibility, osteogenic and angiogenic effects. In the present study, to ensure the mechanical competence of the 45S5 Bioglass(®)-based scaffolds, their stiffness was adjusted by applying polymer coatings and further crosslinking treatment. A non-destructive ultrasonic technique was used to determine the stiffness of the scaffolds.

Effect of individual Fc methionine oxidation on FcRn binding: Met252 oxidation impairs FcRn binding more profoundly than Met428 oxidation.

The long serum half-lives of mAbs are conferred by pH-dependent binding of IgG-Fc to the neonatal Fc receptor (FcRn). The Fc region of human IgG1 has three conserved methionine residues, Met252, Met358, and Met428. Recent studies showed oxidation of these Met residues impairs FcRn binding and consequently affects pharmacokinetics of therapeutic antibodies.

Harnessing big data for health care and research: are urologists ready?

We are at a crossroads in terms of the data we collect and how they are analyzed. In health care, big data analytics may uncover associations, patterns, and trends with the potential to advance patient care and lower costs. To adapt to this approach, urologists will have to ask the right questions.

A high-throughput adrenaline test for the exploration of the catalytic potential of halohydrin dehalogenases in epoxide ring-opening reactions.

The principle of the adrenaline test for enzymes is based on the quantification of periodate-sensitive reaction products with adrenaline to produce a chromogenic compound adrenochrome that can be easily detected. Here, a rapid whole-cell -based adrenaline assay for the activity measurement of halohydrin dehalogenases (HHDHs) in nucleophile-mediated epoxide ring-opening reactions is presented. The assay was validated using two types of model reactions (glycidol with nucleophiles and nitrite with epoxides).

The use of social media in endourology: an analysis of the 2013 World Congress of Endourology meeting.

Objective: To examine the use of social media within Endourology by reporting on its utilization during the 2013 World Congress of Endourology (WCE) annual meeting.

Materials And Methods: Two social media platforms were analyzed for this study: Twitter (San Francisco, CA) and LinkedIn (Mountain View, CA). For Twitter, a third-party analysis service (Tweetreach) was used to quantitatively analyze all tweets with the hashtags #WCE2013 and #WCE13 during a 7-day period surrounding the WCE.

Retrospective analysis of a large patient sample to determine p53 and Ki67 expressions in renal cell carcinoma.

Purpose: This study aimed to investigate the expression of p53 and Ki67 genes in renal cell carcinoma (RCC) and its possible clinical value.

Methods: A retrospective analysis of clinical data from 1239 patients with RCC was performed to explore the relationship between the expression of Ki67 and p53 proteins and tumor stage, grade and prognosis.

Results: p53 expression was not significantly correlated with TNM stage and Fuhrman grade (p>0.

Expression and polymorphisms of T cell immunoglobulin domain and mucin domain protein-1 in thymoma with or without myasthenia gravis.

The present study aimed to investigate the expression and association of the single-nucleotide polymorphism (SNP) -1637A/G in the promoter region of the T cell immunoglobulin domain and mucin domain protein-1 (Tim-1) gene in patients diagnosed with thymoma with or without myasthenia gravis (MG). The expression of Tim-1 was detected using the streptavidin peroxidase immunohistochemical staining method on tissues obtained from thymoma patients with (n=58) and without (n=62) MG. The Tim-1 gene -1637A/G polymorphism was detected using the single allele-specific primer polymerase chain reaction.

Applying MetaMap to Medline for identifying novel associations in a large clinical dataset: a feasibility analysis.

Objective: We describe experiments designed to determine the feasibility of distinguishing known from novel associations based on a clinical dataset comprised of International Classification of Disease, V.9 (ICD-9) codes from 1.6 million patients by comparing them to associations of ICD-9 codes derived from 20.

Heat-shock protein 90 promotes nuclear transport of herpes simplex virus 1 capsid protein by interacting with acetylated tubulin.

Although it is known that inhibitors of heat shock protein 90 (Hsp90) can inhibit herpes simplex virus type 1 (HSV-1) infection, the role of Hsp90 in HSV-1 entry and the antiviral mechanisms of Hsp90 inhibitors remain unclear. In this study, we found that Hsp90 inhibitors have potent antiviral activity against standard or drug-resistant HSV-1 strains and viral gene and protein synthesis are inhibited in an early phase. More detailed studies demonstrated that Hsp90 is upregulated by virus entry and it interacts with virus.

Viruses exploit the function of epidermal growth factor receptor.

Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that regulates cellular homeostatic processes. Following ligand binding, EGFR activates different downstream signalling cascades that promote cell survival, proliferation, motility, and angiogenesis and induces F-actin-dependent EGFR endocytosis, which relocalises the activated receptors for degradation or recycling. The responses that are induced by ligand binding to EGFR, including cell signalling activation, protein kinase phosphorylation and cytoskeletal network rearrangement, resemble those induced by virus infection.

SNX-25a, a novel Hsp90 inhibitor, inhibited human cancer growth more potently than 17-AAG.

17-Allylamino-17-demethoxygeldanamycin (17-AAG), a typical Hsp90 inhibitor derived from geldanamycin (GA), has entered Phase III clinical trials for cancer therapy. However, it has several significant limitations such as poor solubility, limited bioavailability and unacceptable hepatotoxicity. In this study, the anticancer activity and mechanism of SNX-25a, a novel Hsp90 inhibitor, was investigated comparing with that of 17-AAG.

Patient-initiated electronic health record amendment requests.

Background And Objective: Providing patients access to their medical records offers many potential benefits including identification and correction of errors. The process by which patients ask for changes to be made to their records is called an 'amendment request'. Little is known about the nature of such amendment requests and whether they result in modifications to the chart.

Bortezomib induces protective autophagy through AMP-activated protein kinase activation in cultured pancreatic and colorectal cancer cells.

Background: Bortezomib, a selective and potent inhibitor of the proteasome, has demonstrated broad anti-tumor activities in many malignancies. In the current study, we aimed to understand the potential resistance factor of bortezomib in cultured pancreatic and colorectal cancer cells.

Results: We observed that bortezomib-induced protective autophagy in cultured PANC-1 pancreatic cancer cells and HT-29 colorectal cancer cells.

Consumer Demand for Online Dizziness Information: If You Build it, They may Come.

Objective: Dizziness is a common reason patients present to doctors, but effective diagnostic tests and treatments for dizziness are underused. The internet is a way to disseminate medical information and is emerging as an intervention platform. The objective of this study was to describe internet searches for dizziness terms to assess the possible consumer demand for internet-based dizziness diagnostic and treatment tools.

Silencing herpes simplex virus type 1 capsid protein encoding genes by siRNA: a promising antiviral therapeutic approach.

Herpes simplex virus type 1 (HSV-1), a member of the herpesviridae, causes a variety of human viral diseases globally. Although a series of antiviral drugs are available for the treatment of infection and suppression of dissemination, HSV-1 remains highly prevalent worldwide. Therefore, the development of novel antiviral agents with different mechanisms of action is a matter of extreme urgency.

Calcium-signal facilitates herpes simplex virus type 1 nuclear transport through slingshot 1 and calpain-1 activation.

Herpes simplex virus type 1 (HSV-1) can establish its latency in neurons and is associated with virus-induced pathological neurodegeneration in the nervous system. Here we show that viral penetration-induced calcium release facilitated HSV-1 intracellular trafficking through activating slingshot 1 (SSH), a phosphatase regulating actin filament dynamics. More detailed studies revealed that phospholipase C gamma 1, and the inositol 1,4,5-trisphosphate receptor isoform 1 were required for SSH activation.

Mouse organ coefficient and abnormal sperm rate analysis with exposure to tap water and source water in Nanjing reach of Yangtze River.

Organ coefficients (including kidney, testis, liver and spleen coefficient) and abnormal sperm rate were used in our study to reflect the exposure to the Yangzte River water. The concentrations of total dissolved metals and semi-volatile organic compounds in tap and source water were measured by ICP-OES and GC-MS, respectively. After mice were fed with purified water (CK), Nanjing tap water (NJT) and Nanjing source water (NJS) for 90 day, the individual and organs (including kidney, testis, liver and spleen) of each mouse were weighted.

Influence of glycosylation pattern on the molecular properties of monoclonal antibodies.

Glycosylation is an important post-translational modification during protein production in eukaryotic cells, and it is essential for protein structure, stability, half-life, and biological functions. In this study, we produced various monoclonal antibody (mAb) glycoforms from Chinese hamster ovary (CHO) cells, including the natively glycosylated antibody, the enriched G0 form, the deglycosylated form, the afucosylated form, and the high mannose form, and we compared their intrinsic properties, side-by-side, through biophysical and biochemical approaches. Spectroscopic analysis indicates no measureable secondary or tertiary structural changes after in vitro or in vivo modification of the glycosylation pattern.

Inhibition of herpes simplex virus type 1 entry by chloride channel inhibitors tamoxifen and NPPB.

Herpes simplex virus type 1 (HSV-1) infection is very common worldwide and can cause significant health problems from periodic skin and corneal lesions to encephalitis. Appearance of drug-resistant viruses in clinical therapy has made exploring novel antiviral agents emergent. Here we show that chloride channel inhibitors, including tamoxifen and 5-nitro-2-(3-phenyl-propylamino) benzoic acid (NPPB), exhibited extensive antiviral activities toward HSV-1 and ACV-resistant HSV viruses.

The Hsp90 inhibitor SNX-2112 induces apoptosis of human hepatocellular carcinoma cells: the role of ER stress.

Heat shock protein 90 (Hsp90) has been predicted to be involved in hepatocellular carcinoma (HCC) therapy; however, the mechanisms of action remain elusive. SNX-2112 is an Hsp90 inhibitor showing broad antitumor activity. Here we aim to determine the role of the endoplasmic reticulum (ER) stress in SNX-2112-induced apoptosis in HCC cells.

Location bias of identifiers in clinical narratives.

Scrubbing identifying information from narrative clinical documents is a critical first step to preparing the data for secondary use purposes, such as translational research. Evidence suggests that the differential distribution of protected health information (PHI) in clinical documents could be used as additional features to improve the performance of automated de-identification algorithms or toolkits. However, there has been little investigation into the extent to which such phenomena transpires in practice.