tbuckley/cabot-search huggingface dataset:
Soluble VE-cadherin is involved in endothelial barrier breakdown in systemic inflammation and sepsis
Authors: S. Flemming, N. Burkard, M. Renschler, F. Vielmuth, M. Meir, M. A. Schick, C. Wunder, C.-T. Germer, V. Spindler, J. Waschke, N. Schlegel
Journal: Cardiovascular Research (2015)

Microvascular endothelial barrier breakdown in sepsis precedes organ failure and death in patients. We tested the hypothesis that the formation of endothelium-derived soluble vascular endothelial (VE)-cadherin fragments (sVE-cadherin) is involved in inflammation-induced endothelial barrier disruption. Incubation of human dermal microvascular endothelial cells (HDMEC) with tumour necrosis factor-α (TNF-α) and bacterial lipopolysaccharide (LPS) led to endothelial barrier disruption which correlated with significantly increased sVE-cadherin at a size of ∼90 kDa in cell culture supernatants. Inhibition of the VE-cadherin-cleaving disintegrin and metalloproteinase ADAM10 using GI254023X attenuated inflammation-induced formation of sVE-cadherin and endothelial barrier disruption, suggesting ADAM10-mediated shedding as a mechanism underlying sVE-cadherin release. Formation of VE-cadherin fragments at 90 and 110 kDa was observed when recombinant VE-cadherin (rVE-cadherin) was digested with recombinant ADAM10. Mass spectrometry of the VE-cadherin fragments showed that they originated from cleavage of the extracelluar domain and thereby several cleavage sites of ADAM10 were identified. Atomic force microscopy measurements demonstrated that cell culture supernatants containing sVE-cadherin and application of rVE-cadherin blocked VE-cadherin binding. Accordingly rVE-cadherin dose-dependently led to loss of endothelial barrier functions in HDMEC monolayers. Finally, in patients suffering from severe sepsis or septic shock with clinical signs of a microvascular leackage, serum levels of sVE-cadherin were significantly increased. Taken together, formation of sVE-cadherin is associated and contributes to inflammation-induced breakdown of endothelial barrier functions by inhibition of VE-cadherin binding. The underlying mechanism of VE-cadherin cleavage involves ADAM10 and appears to be of clinical relevance since sVE-cadherin was augmented in patients with severe sepsis.
Radiation-recall dermatitis in a patient treated with paclitaxel.
Authors: K A Phillips, M Urch, J F Bishop
Journal: Journal of Clinical Oncology (1995)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1995.13.1.305 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 7799038 Radiation-recall dermatitis in a patient treated with paclitaxel. K A PhillipsxK A PhillipsSearch for articles by this author , M UrchxM UrchSearch for articles by this author , J F BishopxJ F BishopSearch for articles by this author https://doi.org/10.1200/JCO.1995.13.1.305 PDF "Radiation-recall dermatitis in a patient treated with paclitaxel.." Journal of Clinical Oncology, 13(1), p. 305© 1995 by American Society of Clinical Oncology
Afatinib alone or afatinib plus vinorelbine versus investigator's choice of treatment for HER2-positive breast cancer with progressive brain metastases after trastuzumab, lapatinib, or both (LUX-Breast 3): a randomised, open-label, multicentre, phase 2 trial
Authors: Javier Cortés, Véronique Dieras, Jungsil Ro, Jérôme Barriere, Thomas Bachelot, Sara Hurvitz, Emilie Le Rhun, Marc Espié, Sung-Bae Kim, Andreas Schneeweiss, Joo Hyuk Sohn, Jean-Marc Nabholtz, Pirkko-Liisa Kellokumpu-Lehtinen, Julie Taguchi, Federico Piacentini, Eva Ciruelos, Petri Bono, Mahmoud Ould-Kaci, Flavien Roux, Heikki Joensuu
Journal: The Lancet Oncology (2015)
The Predictive and Prognostic Value of Early Metabolic Response Assessed by Positron Emission Tomography in Advanced Gastric Cancer Treated with Chemotherapy
Authors: Chenchen Wang, Weijian Guo, Min Zhou, Xiaodong Zhu, Dongmei Ji, Wenhua Li, Xin Liu, Zhonghua Tao, Xiaowei Zhang, Yingjian Zhang, Jin Li
Journal: Clinical Cancer Research (2015)

To evaluate the feasibility of early metabolic change assessed by PET in predicting clinical response to chemotherapy and investigate its prognostic value in patients with advanced gastric cancer.A total of 64 patients with advanced gastric cancer were prospectively enrolled and examined by PET with (18)F-fluorodeoxyglucose (FDG) and (18)F-fluoro-3'-deoxy-3'-L-fluorothymidine (FLT) at baseline and 14 days after treatment initiation. PET findings were analyzed for the correlation with best clinical response of patients, disease control status, and survival after identifying the threshold of metabolic change percentage by ROC analysis.For FDG-PET, the total uptake value reduction percentage (δ-SUV) of 40% was the cut-off point with the maximum of sensitivity (70%) and specificity (83%) to predict clinical responding and that of prediction for disease control status was 30%, with the highest sensitivity (58%) and specificity (100%). The δ-SUV of FLT-PET played no predictive role for clinical response (AUC = 0.62; P= 0.134) and disease control (AUC = 0.66; P= 0.157). The univariate Cox regression analysis revealed no significant prognostic impact. FDG uptake reduction in liver metastases could predict both clinical response (P= 0.010) and disease control status (P= 0.002) at thresholds of 35% and 15%, respectively. Those with greater FDG uptake reduction in liver lesions had a longer overall survival (P= 0.004).Early metabolic change in FDG-PET might be a predictive marker for response and disease control in advanced gastric cancer. Early FDG uptake change in liver metastases might be a useful prognostic factor and needs further exploration.
Rapid characterization of CRISPR-Cas9 protospacer adjacent motif sequence elements
Authors: Tautvydas Karvelis, Giedrius Gasiunas, Joshua Young, Greta Bigelyte, Arunas Silanskas, Mark Cigan, Virginijus Siksnys
Journal: Genome biology (2015)

To expand the repertoire of Cas9s available for genome targeting, we present a new in vitro method for the simultaneous examination of guide RNA and protospacer adjacent motif (PAM) requirements. The method relies on the in vitro cleavage of plasmid libraries containing a randomized PAM as a function of Cas9-guide RNA complex concentration. Using this method, we accurately reproduce the canonical PAM preferences for Streptococcus pyogenes, Streptococcus thermophilus CRISPR3 (Sth3), and CRISPR1 (Sth1). Additionally, PAM and sgRNA solutions for a novel Cas9 protein from Brevibacillus laterosporus are provided by the assay and are demonstrated to support functional activity in vitro and in plants.
Prospective Study on Quality of Life Before and After Radical Radiotherapy in Non–Small-Cell Lung Cancer
Authors: J. A. Langendijk, N. K. Aaronson, J. M.A. de Jong, G. P.M. ten Velde, M. J. Muller, R. J. Lamers, B. J. Slotman, E. F.M. Wouters
Journal: Journal of Clinical Oncology (2001)

PURPOSE: The purpose of this study was to investigate changes in respiratory symptoms and quality of life (QoL) in patients with non–small-cell lung cancer (NSCLC) receiving radical radiotherapy (60 Gy). Additionally, the association between the level of symptom relief and objective tumor response, as well as with radiation-induced pulmonary changes, was investigated. PATIENTS AND METHODS: One hundred sixty-four patients were entered onto this prospective study. The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 and EORTC QLQ-LC13 were used to investigate changes in QoL. Assessments were performed before radiotherapy and 2 weeks, 6 weeks, 3 months, 6 months, and 12 months after the completion of radiotherapy. RESULTS: The QoL response rates were excellent for hemoptysis (83%); good for chest pain (68%), arm/shoulder pain (63%), and appetite loss (60%); and poor for dyspnea (37%), cough (31%), and fatigue (28%). The QoL response rates for the five functioning scales of the QLQ-C30 varied from 35% for physical and role functioning to 55% for social and cognitive functioning. The response rate for global QoL was 36%. A significant association was found between tumor response and palliation of chest pain, arm/shoulder pain, and physical functioning. During radiotherapy, a significant increase for most general symptoms and a deterioration in functioning and QoL were noted. CONCLUSION: This study is the first to describe palliation and changes in QoL in radically irradiated patients with NSCLC. Radical radiotherapy offers palliation of respiratory symptoms and improved QoL in a substantial proportion of patients with NSCLC who have relatively good prognostic features. Although tumor reduction is associated with palliation of respiratory symptoms, it cannot serve as a surrogate for palliation.
Integrative Systems Research on the Brain: Resurgence and New Opportunities
Authors: Theodore H. Bullock
Journal: Annual Review of Neuroscience (1993)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More
Definition of Specificity in a Screening Trial
Authors: Paul F. Pinsky
Journal: Journal of Clinical Oncology (2015)

TO THE EDITOR: In the abstract of the article by Menon et al, the authors report that the multimodal strategy for ovarian cancer screening had a specificity of 99.8%. However, in an examination of the results presented in the body of the paper, approximately 10% of screenings in women without ovarian cancer had results that were denoted as elevated or intermediate, both of which require some additional diagnostic testing before the next scheduled screen, whereas 90% had a fully negative result. Therefore, by the conventional definition of specificity as the proportion of patients without cancer who have negative screening tests, the specificity of the multimodal strategy was only 90%. The 99.8% specificity value, or conversely, the 0.2% value for 1002 specificity, was derived as the percentage of screenings in women without ovarian cancer that were elevated or intermediate and that resulted in surgery. This way of defining specificity is misleading. For example, the National Lung Screening Trial reported a false-positive rate (1002 specificity) with low-dose computed tomography screening of approximately 23%. Quite correctly, this high false-positive rate raised concerns about the harms and costs of low-dose computed tomography screening. By a definition analogous to the one used here, however, the false-positive rate in the National Lung Screening Trial would have been only 0.6% on the basis of the proportion of screenings in patients without lung cancer that were positive and who had an invasive diagnostic followup procedure (ie, 457 of 74,433). Invasive procedures in patients without cancer are, of course, a major cause for concern; however, any screening result in such patients that requires some diagnostic follow-up, including a repeat screening, induces costs and potential harms and should be counted against test specificity. Furthermore, specificity should be reported in a uniform manner, so readers will understand to what the term refers.
Checkpoint Kinase 2 Negatively Regulates Androgen Sensitivity and Prostate Cancer Cell Growth
Authors: Huy Q. Ta, Melissa L. Ivey, Henry F. Frierson, Mark R. Conaway, Jaroslaw Dziegielewski, James M. Larner, Daniel Gioeli
Journal: Cancer Research (2015)

Abstract Prostate cancer is the second leading cause of cancer death in American men, and curing metastatic disease remains a significant challenge. Nearly all patients with disseminated prostate cancer initially respond to androgen deprivation therapy (ADT), but virtually all patients will relapse and develop incurable castration-resistant prostate cancer (CRPC). A high-throughput RNAi screen to identify signaling pathways regulating prostate cancer cell growth led to our discovery that checkpoint kinase 2 (CHK2) knockdown dramatically increased prostate cancer growth and hypersensitized cells to low androgen levels. Mechanistic investigations revealed that the effects of CHK2 were dependent on the downstream signaling proteins CDC25C and CDK1. Moreover, CHK2 depletion increased androgen receptor (AR) transcriptional activity on androgen-regulated genes, substantiating the finding that CHK2 affects prostate cancer proliferation, partly, through the AR. Remarkably, we further show that CHK2 is a novel AR-repressed gene, suggestive of a negative feedback loop between CHK2 and AR. In addition, we provide evidence that CHK2 physically associates with the AR and that cell-cycle inhibition increased this association. Finally, IHC analysis of CHK2 in prostate cancer patient samples demonstrated a decrease in CHK2 expression in high-grade tumors. In conclusion, we propose that CHK2 is a negative regulator of androgen sensitivity and prostate cancer growth, and that CHK2 signaling is lost during prostate cancer progression to castration resistance. Thus, perturbing CHK2 signaling may offer a new therapeutic approach for sensitizing CRPC to ADT and radiation. Cancer Res; 75(23); 5093–105. ©2015 AACR.
Bioinspired anchoring AgNPs onto micro-nanoporous TiO2 orthopedic coatings: Trap-killing of bacteria, surface-regulated osteoblast functions and host responses
Authors: Zhaojun Jia, Peng Xiu, Ming Li, Xuchen Xu, Yuying Shi, Yan Cheng, Shicheng Wei, Yufeng Zheng, Tingfei Xi, Hong Cai, Zhongjun Liu
Journal: Biomaterials (2015)
Influx of Thyroid Hormones into Rat Liver In Vivo
Authors: William M. Pardridge, Lawrence J. Mietus
Journal: Journal of Clinical Investigation (1980)

The transport of [(125)I]thyroxine (T(4)) and [(125)I]triiodothyronine (T(3)) into liver was investigated with a tissue sampling-portal vein injection technique in the anesthetized rat. The method allows the investigation of the effects of plasma proteins in human serum on the unidirectional influx of T(4) or T(3) into liver cells. The percent extraction of unidirectional clearance of T(3) and T(4) was 77+/-2% and 43+/-2%, respectively, after portal injection of a bolus of Ringer's solution. Cell membrane transport of T(4) or T(3) was nonsaturable because 50-muM concentrations of unlabeled hormone had no effect on transport. The addition of bovine albumin in concentrations of 1, 5, or 10 g/100 ml bound >98% of T(4) or T(3) in vitro, but had no significant effect on T(3) or T(4) transport in vivo. Conversely, 10% rabbit antisera specific for T(3) or T(4), completely abolished the intracellular distribution of thyroid hormone into liver. In the presence of rat serum, which contains albumin and thyroid hormone binding pre-albumin (TBPA), 18 and 81% of total plasma T(4) and T(3), respectively, were available for transport in vivo. The fraction of hormone available for transport in the presence of normal human serum, which contains albumin, TBPA, and thyroid hormone binding globulin (TBG) was 11% for T(4) and 72% for T(3). The fraction of hormone transported into liver after injection of serum obtained from pregnant or birth control pilltreated volunteers was 4% for T(4) (but this was not significantly different from zero) and 54% for T(3). THESE DATA SUGGEST: (a) The mechanism by which T(4) and T(3) traverse the liver cell membrane is probably free diffusion. (b) Albumin-bound T(4) or T(3) is freely cleared by liver, approximately 50% of TBG-bound T(3) is transported, but little, if any, of TBPA-bound T(4) or TBG-bound T(4) is cleared by liver cells. (c) Although the albumin-bound fraction of T(4) greatly exceeds the free (dialyzable) moiety, the two fractions are both inversely related to the existing TBA or TBG level; therefore, in vitro measurements of free T(4) would be expected to accurately reflect what is available for transport in vivo. Conversely, TBG-bound T(3) is readily transported in vivo; therefore, it is proposed that in vitro measurements of free T(3) do not reliably predict the fraction of T(3) available for transport into liver in vivo.
Efficacy of Oral Immunotherapy and Anti-IgE Antibody-Adjunctive Treatment in Patients with Multiple Food Allergies
Authors: Tina L.R. Dominguez, Shruti P. Wilson, Alicia Sciancalepore, Daniela Pineda, Anjuli Mehrotra, Steven W. Rubinstein, Alan B. Goldsobel, Michael J. Mulligan, Robert C. Bocian, Nancy Cummings, Kari Nadeau
Journal: Journal of Allergy and Clinical Immunology (2013)
P-158 (BREGO) Regorafenib combined with modified (m) GEMOX (Gemcitabine- Oxaliplatin) in patients with advanced biliary tract cancer (BTC): a phase Ib/II randomized trial
Authors: E. Assenat, J.-P. Delord, S. Thézenas, E. Samalin, F. Portales, C. Sari, A. Thirion, R. Guimboaud, M. Ychou
Journal: Annals of Oncology (2015)
Geographically predominant genotypes of Aspergillus terreus species complex in Austria: s microsatellite typing study
Authors: M. Lackner, S. Coassin, M. Haun, U. Binder, F. Kronenberg, H. Haas, M. Jank, E. Maurer, J.F. Meis, F. Hagen, C. Lass-Flörl
Journal: Clinical Microbiology and Infection (2015)
Future of General Practice
Authors: Mike Fitzpatrick
Journal: BMJ (1967)

Sometime around last Christmas, the patient editor of the British Medical Journal , had a dream, indeed a vision, of how the health of the nation would improve over the decade ahead.

 ‘As people began to realise that preventing themselves from becoming unwell was infinitely preferable to having avoidable illnesses treated, they started to listen more carefully to the government's health promotion messages: eating more healthily, drinking more sensibly, taking more exercise, and avoiding unnecessary exposure to the sun. Generally, the media helped move the process along. In particular, they played a major part in making drug misuse completely unfashionable.’ 1

My first thought was that this was some sort of spoof. But no, it was published on the day after the Epiphany, not on 1 April. As this editorial begins with some references to Dougal and Zebedee of the Magic Roundabout …
An Evaluation of the Role of Calcium in Cell Injury
Authors: A W Harman, M J Maxwell
Journal: The Annual Review of Pharmacology and Toxicology (1995)

It has been proposed that a number of chemical-induced cell injuries result from disruption of the ability of the cell to control calcium. Many of the techniques used to develop this theory have relied on indirect measurements of intracellular calcium. The advent of digital imaging fluorescence microscopy has allowed a more direct examination of the relationship between calcium and cell damage. Results indicate that cytosolic calcium does not play a central role in the initiation of oxidative injury in a number of cell types. Changes in calcium homeostasis occur well after the appearance of other indications of cell injury. However, recent studies indicate that a mitochondrial lesion occurs relatively early in the time course of oxidative cell injury. Calcium may play a role in the development of this lesion.
Abstract #4775: The selective aurora B kinase inhibitor AZD1152-HQPA inhibits in vitro growth of small cell lung cancer (SCLC) cell lines
Authors: Barbara Helfrich, Mariana Theodoro, Marilelia Varella-Garcia, Jerry Haney, Lynne Bemis, Paul Bunn
Journal: Cancer Research (2009)

Background:  Aurora B kinase (AURKB) regulates cytokinesis and is overexpressed in a range of cancers. We investigated the effects of the selective aurora B kinase inhibitor AZD1152-HQPA in a panel of 14 SCLC lines among which p53 was mutant in 12 of these and Rb was mutant in 6 cell lines (wild type in 5 lines and 3 unknown).  Methods:  Growth inhibition by AZD1152-HQPA was assessed by MTT assays at 6 days. DNA ploidy, cell cycle arrest and AURKB protein expression were assessed by FACS. AURKB gene copy number was evaluated by FISH. MicroRNA (miR) expression was determined using microRNA chips.  Results:  AZD1152-HQPA treatment inhibited growth of all 14 of the cell lines. The 4 most sensitive lines had IC 50 s in the therapeutically relevant range of 5-100 nM and less then 25% of control growth was observed at concentrations > 100nM. Five cell lines had IC 50  values of 30-100nM but cell viability at 100nM in these lines was 40-50% of untreated control. The remaining 5-lines showed less then 25% growth inhibition in a 6-day assay. Extended 12 day assay at 100nM showed a reduction in viable cells to 14-20% of untreated control cells in 7 of the less sensitive cell lines. All cell lines had high AURKB gene expression by Affymetrix arrays (mean 831 ± 210) compared to normal lung (mean 7.7 ± 3.99) and high protein expression by FACS (mean 80% pos ± 6 and fl intensity 5.3 ± 0.25). There was no significant correlation between AURKB gene or protein expression and sensitivity to AZD1152-HQPA. Loss of miR-570 and miR-765 which inhibit AURKB mRNA expression was found in 8/8 lines and there was an inverse correlation with gene and protein expression but not AZD1152-HQPA sensitivity. Similarly p53 and Rb mutational status did not correlate with sensitivity to AZD1152-HQPA. By FISH analysis all cell lines had low AURKB gene copy number (mean 2.34 ± 0.082) and no amplification was found. Marked increases in DNA ploidy (8N and 16N) were observed after 24 hour exposure to AZD1152-HQPA (50nM) in the most sensitive cell lines, were less striking in cell lines with intermediate sensitivity and were not observed in the most resistant lines.  Conclusions:  AZD1152-HQPA inhibited the growth of SCLC lines and induced increases in DNA ploidy. AZD1152-HQPA sensitivity was not related to AURKB gene expression or protein expression or miR520 or miR765 expression. Future studies will evaluate cell death mechanisms and we will search for other biomarkers that correlate with changes in DNA ploidy.   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 4775.
FibroGENE: A gene-based model for staging liver fibrosis
Authors: Mohammed Eslam, Ahmed M. Hashem, Manuel Romero-Gomez, Thomas Berg, Gregory J. Dore, Alessandra Mangia, Henry Lik Yuen Chan, William L. Irving, David Sheridan, Maria Lorena Abate, Leon A. Adams, Martin Weltman, Elisabetta Bugianesi, Ulrich Spengler, Olfat Shaker, Janett Fischer, Lindsay Mollison, Wendy Cheng, Jacob Nattermann, Stephen Riordan, Luca Miele, Kebitsaone Simon Kelaeng, Javier Ampuero, Golo Ahlenstiel, Duncan McLeod, Elizabeth Powell, Christopher Liddle, Mark W. Douglas, David R. Booth, Jacob George
Journal: Journal of Hepatology (2015)
Epidemic Cerebro-Spinal Meningitis in Dublin
Authors: A. R. Parsons, H. E. Littledale
Journal: BMJ (1900)

congenital heart disease or pyloric stenosis or diaphragmatic hernia, and necessitate the most careful application of all our diagnostic methods.Finally, the placenta and membranes and cord ought always to be scrutinised, and when possible submitted to microscopical and bacteriological examination.