tbuckley/cabot-search huggingface dataset:
Reporting data on long-term follow-up of critical care trials
Authors: May Hua, Hannah Wunsch
Journal: Thorax (2016)

Over the past 20 years, the lens of critical care research has widened, with 60 or 90 days becoming an increasingly common end point for observation of mortality and other outcomes.1–6 There have also been an increase in studies that follow patients for many years to understand how and when recovery occurs and whether risks attributable to critical illness may diminish.7–9 Correspondingly, when new therapies aimed at improving outcomes are studied, there is increasing recognition that reporting of short-term (ie, hospital) outcomes is not enough and that evaluation of the long-term effects of the intervention can be very important.

Dinglas et al present long-term follow-up data of patients enrolled in the Statins in Acutely Injured Lungs in Sepsis (SAILS) trial, which examined the use of rosuvastatin in patients with sepsis-associated acute respiratory distress syndrome (ARDS).10 The SAILS trial randomised patients within 48 h of enrolment to receive either rosuvastatin or placebo for a maximum of 28 days (or until the third day after discharge from the intensive care unit (ICU), hospital discharge or death). The primary outcome of the original study was 60-day in-hospital mortality. As part of the planned analysis, the authors evaluated the long-term outcome of these patients to determine the safety of in-hospital statin use in survivors of sepsis-associated ARDS.11 The rationale was that there are known adverse effects of statins on skeletal muscle and psychological symptoms that can occur, and critically ill patients represent a population already at risk of physical and psychological difficulties.

The authors collected detailed data on physical performance and psychological symptoms at 6 and …
Abstract 3456: RNA and microRNA analysis of diffused intrinsic pontine glioma specimens
Authors: Annie E. Sandza, Ashley Hill, Tobey MacDonald, Javad Nazarian
Journal: Cancer Research (2011)

Abstract Diffused intrinsic pontine glioma (DIPG) is one of the most difficult pediatric cancers to treat. To date, there is only limited information on the molecular characteristics of this tumor because of the paucity of adequate tissue for investigation due to its inoperable location within the brainstem. In an attempt to uncover the pathogenesis of DIPG, we have generated comprehensive molecular profiles of coding and non-coding RNA species obtained from pediatric DIPG autopsy specimens. Coding and non-coding RNA species play an important role in oncogenesis. Micro RNAs (miRNAs or miRs) are the more recent non-coding RNA species that have been shown to play an essential role in cancer development and cancer biology. Our aim was to gain insight into the molecular underpinnings of DIPG by generating the complete miRNA and mRNA profiles of the tumor. Autopsy DIPG specimens were analyzed (n=3). Adjacent non-tumor areas were identified by a neuropathologist and used as controls. Total RNA was extracted and coding and non-coding small RNA were profiled using the Affymetrix platform. A total of 60 miRNA species were found to be dysregulated in DIPG tumor compared to adjacent normal section. Of these, 12 were known human micro RNAs. RNA species that showed to be dysregulated were further validated by RT-PCR (ABI platform). Furthermore, correlation analyses were done to assess expression levels of mRNAs and their corresponding miRs. Our preliminary data indicates specific dysregulation of micro RNA and RNA species that control cellular proliferation and tumorigenesis. Although preliminary, this is to our best knowledge, the first report of comprehensive RNA profiling of DIPG. Correlation of coding and non-coding RNA species observed here will require further validation. Understanding the molecular makeup of DIPG will provide insight into its pathogenesis and perhaps lead to the development of targeted therapeutics for this disease. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3456. doi:10.1158/1538-7445.AM2011-3456
Abstract 2729: Galectin-4 in colorectal cancer
Authors: Arun Satelli, Prema S. Rao, U Subrahmanyeswara Rao
Journal: Cancer Research (2010)

Abstract Introduction: Colorectal cancer (CRC) is one of the leading diseases in the western world and is curable if diagnosed at an early stage. The normal-adenoma-carcinoma sequence concept suggests that the normal epithelia in the colorectal region transform into adenomas, which progress to invasive carcinomas. The role of galectin-4 (gal-4) a protein abundantly expressed in normal colonic epithelia, hereto considered a differentiation marker, on the onset or progression of colorectal cancer (CRC) is unknown. The main aim of this study is to evaluate gal-4 as a potential biomarker in detecting the onset of CRC and to determine the function of gal-4 in CRC development. Methods: We analyzed the paraffin-embedded normal, adenomatous polyps and invasive carcinomas of the human colon biopsies and tissue microarrays for gal-4 expression by immunohistochemistry. Gal-4 expression in CRC cell lines was characterized by RT-PCR, western blotting, immunofluorescence microscopy and FACS analysis. The functional role of gal-4 was examined by cell proliferation, migration, motility, transfection and RNAi experiments. Results: Biopsies immunostained for gal-4 were quantified using ImageJ software. The normal tissue as well as normal tissue adjacent to cancer contained highest amount of gal-4. Gal-4 intensity decreased in all the disease-states, which was found to be statistically significant (P &amp;lt;0.05). The results suggested that as the normal colon develops adenomatous polyps, which transform subsequently into invasive carcinomas, the epithelial cells lining the crypts shut off gal-4 expression. Gal-4 negative cells showed increased cell proliferation, motility and migration, in comparison to gal-4 positive CRC cells. Transfection of the CRC cells (gal-4 -ve) with gal-4 led to decreased motility and cell cycle arrest. Externally added gal-4 on gal-4 -ve cells induced retarded cell migration. Gal-4 down-regulates cyclin D1 level and upregulates p15 and p21 levels. Conclusions: We conclude that galectin-4 plays a key role the maintenance of epithelial cells in a differentiated state, and its loss allows the cells to de-differentiate, leading to increased cell proliferation, migration and motility, which are hallmark features of cancer. Galectin-4 brings about these changes through cell cycle regulation by modulating the cyclin D1, p15 and p21 levels. Finally, our findings that extracellular galectin-4 retards the migratory potential raise a possibility for it to serve as a therapeutic agent in controlling CRC progression. Thus beyond shedding light on the role of tumor-suppressor gal-4 in CRC, this study underscores the potential clinical value of gal-4 in prognosis and diagnosis of CRC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2729.
INFLUENCE OF AGE ON THE PROGNOSTIC PERFORMANCE OF BRAIN NATRIURETIC PEPTIDES: THE AGES REYKJAVIK STUDY
Authors: Anders M. Greve, Erik Schelbert, Lenore Launer, Tamara Harris, Gudmundur Thorgeirsson, Gudny Eiriksdottir, Gina LaRocca, Thor Aspelund, Vilmundur Gudnason, Andrew Arai
Journal: Journal of the American College of Cardiology (2015)
LL-01 * THE RELATIONSHIP BETWEEN B2M AND CNS LYMPHOMA
Authors: A. Ghiaseddin, R. Snook
Journal: Neuro-Oncology (2014)

Several laboratory abnormalities may be seen in patients with CNS Lymphoma. Abnormalities often seen include levels of certain proteins, cell volume/morphology, as well as markers of humoral and cell mediated processes. We therefore retrospectively studied the CSF B2M levels in 49 patients to test the sensitivity of this marker in predicting CNS Lymphoma. Based on our pilot study, the sensitivity for elevated CSF B2M was 100% in patients with CNS Lymphoma. The specificity for elevated CSF B2M was 61%. Our results suggest CSF B2M is a highly sensitive marker of CNS Lymphoma. However, CSF B2M was not found to be a highly specific marker of CNS Lymphoma. Future studies will need to include larger sample sizes to increase accuracy.
S148 Regulation of neutrophil apoptosis by phosphoinositide 3-kinases
Authors: J. K. Juss, A. M. Condliffe, P. T. Hawkins, L. Stephens, E. R. Chilvers
Journal: Thorax (2010)

<h3>Introduction</h3> Neutrophils are an essential component of the innate immune response. However, their microbicidal mechanisms (generation of reactive oxygen species and release of proteolytic enzymes) may contribute to tissue injury. Neutrophil-mediated tissue damage is a cardinal feature in the pathogenesis/progression of COPD, cystic fibrosis and certain types of asthma. Apoptosis is the key determinant of tissue neutrophil longevity and is critical to the resolution of granulocyte inflammation; pharmacological acceleration of neutrophil apoptosis can promote resolution of inflammation in animal models. The cytokine GM-CSF drives the aberrant neutrophil survival phenotype observed in patients with ARDS, and recent studies suggest the phosphoinositide 3-kinase (PI3K)/AKT pathway is pivotal in signalling GM-CSF-mediated neutrophil survival. <h3>Hypothesis</h3> Given the emerging evidence that individual Class I PI3K isoforms (α, β, δ and γ) exert non-redundant signalling roles and represent promising therapeutic targets in inflammation, we hypothesised a distinct contribution of individual Class I PI3K isoforms in mediating constitutive neutrophil apoptosis and the GM-CSF cytoprotective effect. <h3>Methods</h3> We established techniques to isolate peripheral blood neutrophils from humans and from knockout/transgenic mice lacking functional PI3K isoforms to 95% purity, and used pan-PI3K inhibitor (LY294002), pan-Class I PI3K inhibitor (PI-103) and novel PI3K isoform-selective small molecule inhibitors (YM-024, TGX-221, IC87114 and AS605240) to determine precise involvement of Class I PI3K isoforms (α, β, δ and γ) in constitutive and GM-CSF-delayed neutrophil apoptosis. Apoptosis was quantified using morphology and annexin V-FITC/propidium iodide staining. <h3>Results</h3> GM-CSF-mediated neutrophil survival was reversed by pan-PI3K inhibition but not by individual PI3K isoform inhibition. Combinatorial experiments suggest there is near-complete functional redundancy amongst Class I PI3Ks with regard to GM-CSF-mediated inhibition of neutrophil apoptosis; additionally, neutrophils derived from double knockout PI3K-δ/γ and PI3K-β/δ mice had normal constitutive apoptosis and GM-CSF mediated survival, but were sensitised to inhibition of the remaining isoforms. <h3>Conclusions</h3> Thus Class I PI3Ks mediate GM-CSF survival of human and murine neutrophils but there is complete functional redundancy of the PI3K isoforms, necessitating multiple isoform inhibition to reverse GM-CSF-induced neutrophil survival. This finding informs our understanding of the mechanisms regulating neutrophil apoptosis and suggests neutrophil survival would be resilient to individual isoform-selective PI3K inhibitors.
Phase II Clinical Study of Protection of Nail Change and Skin Toxicity by Using a Frozen Glove in Japanese Patients with Early Breast Cancer Treated by Docetaxel and Cyclophosphamide (TC) [TBCRG-03 Study].
Authors: T. Hayashi, T. Fujita, T. Mase, S. Nakano, M. Wada, T. Kashizuka, H. Sugiura, T. Mizuno, H. Iwata, Y. Ohashi
Journal: Cancer Research (2009)

Abstract Background: The combination docetaxel with cyclophosphamide (TC) regimen is one of standard treatment for early breast cancer patients. TC regimen has been widely used in Japan. However, a management for adverse event such as especially edema and nail/skin toxicity by docetaxel is very important due to give a completely full dosage. This multicenter phase II study was designed to evaluate the protection of nail and skin toxicity by using a frozen glove for early breast cancer patients treated by TC.Methods: Four cycles of docetaxel (75mg/m2) and cyclophosphamide (600mg/m2) administered intravenously (i.v.) every 21 days after surgery for primary breast cancer. All patients were attached frozen glove at right or left hand (protected hand) from 15 minutes before to 30 minutes after administration of docetaxel. The other hand (control hand) of same patient is not attached frozen glove between a administration of TC. Safety was assessed every cycle after the start of treatment. Primary endpoint is comparison the rates of nail and skin toxicity between protected and control hand. Secondary endpoints are feasibility of adjuvant TC regimen and adverse events by frozen glove in Japanese women.Results: Fifty two patients were enrolled from September 2007 to June 2008. The nail changes (grade 1 and 2) was occurred in 10 events (19.2%) and 19 events (36.5%) at protected and control hand, respectively. The skin toxicity was occurred in 14 events (26.9%, G1:8, G2:6) and 21 events (40.4%, G1:14, G2:7) at protected and control hand, respectively. The appearance of nail and skin toxicity was significantly decreased at protected hand than control hand (p=0.01). Overall, 41 patients (78%) completed the planned four cycles of TC without dose reductions or study discontinuation. One patient discontinued because of hematological toxicity defined as discontinuation by protocol. The dose reductions were necessary in 10(19%) patients because of hematological (febrile neutropenia) and non hematological toxicity by TC. Grade 3 and 4 adverse events (AEs) were neutropenia (G3:3.9%, G4:21.6%), febrile neutropenia (21.2%), fatigue (1.9%) and dermatitis (3.8%). Grade 1 or 2 AEs frequently observed (more than 20%) were dermatitis such as rash (45%, G1:29.4%, G2:15.7%), pigmentation, nausea, anorexia, disturbance of taste, tear dropping, fatigue, edema and peripheral sensory disturbance. However, there are no adverse events by frozen glove.Conclusion: TC is feasible regimen for early Japanese breast cancer patients after surgery. Frozen glove may be useful procedure which protected the nail and skin toxicity. Furthermore, it is necessary to protect the severe dermatitis due to completely performed planned TC treatment after surgery in Japan. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 808.
Abstract 1547: Characterization of receptor-ligand interactions between head and neck circulating tumor cells and E-selectin
Authors: Jocelyn R. Marshall, Nathan M. Reynolds, Courtney E. Abram, Karissa A. Henson, S. Matthew Wood, Leonardo Nimrichter, Monica M. Burdick
Journal: Cancer Research (2011)

Abstract Though the exact mechanisms of cancer metastasis are not known, it is widely believed that circulating tumor cells (CTCs) that have broken off from the primary tumor flow through the blood stream until ligands on their surface recognize receptors present on the vascular endothelium. From there, CTCs loosely attach to the endothelium surface and roll until they become firmly adherent. Cells then migrate through the blood vessel walls to establish metastatic colonies in a distant organ. Therefore, identifying the molecular structures available for adhesion on the surface of the CTCs is compulsory to fully understanding the ubiquitous and unique natures of cancer metastasis. We have previously shown that the adhesion of head and neck squamous cell carcinomas (HNSCCs) to human umbilical vascular endothelium cells (HUVECs) under flow is mediated by E-selectin present on the endothelium surface. In this study, we investigated the interaction of E-selectin with ligands present on the HNSCC surface. Protease-treated cells of the JHU-011-SCC, JHU-013-SCC, and FaDu cell lines perfused through the parallel-plate flow chamber tethered to and rolled on the HUVECs at a greater incidence rate compared to untreated control cells. These binding interactions were sialidase and fucosidase sensitive. Altogether, these results indicate that sialofucosylated glycolipids on HNSCC cells predominantly contribute to the adhesion of these cells to endothelium. This observation was further confirmed by probing western blots of SDS-PAGE resolved HNSCC lysates with HECA-452 mAb and E-selectin chimera. Neither probe was reactive with protein species. We also tested if a shielding effect of hyaluronic acid (HA) prevented glycosphingolipid engagement to E-selectin. When HNSCC cells were treated with HAse and when hyaluronic acid synthase-3 was silenced by shRNA, there was an increase in cell adhesion events. These results clearly demonstrate that proteins and HA exert shielding effects on the E-selectin glycolipid ligands, thus affecting the overall metastatic ability of the HNSCCs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1547. doi:10.1158/1538-7445.AM2011-1547
TELOMERE LENGTH VARIANTS ARE ASSOCIATED WITH HIGH-GRADE GLIOMA RISK: IDENTIFICATION OF A NOVEL GLIOMA RISK LOCUS BY GENOME-WIDE ASSOCIATION STUDY
Authors: K. M. Walsh, K. M. Walsh, V. Codd, I. V. Smirnov, T. Rice, P. A. Decker, H. M. Hansen, T. Kollmeyer, M. L. Kosel, A. M. Molinaro, L. S. McCoy, P. M. Bracci, B. S. Cabriga, M. Pekmezci, S. Zheng, J. L. Wiemels, A. R. Pico, T. Tihan, M. S. Berger, S. M. Chang, M. D. Prados, D. H. Lachance, B. P. O'Neill, H. Sicotte, J. E. Eckel-Passow, P. van der Harst, J. K. Wiencke, N. J. Samani, R. B. Jenkins, M. R. Wrensch
Journal: Neuro-Oncology (2014)

BACKGROUND: Glioblastoma, the most common and aggressive form of glioma, has a median survival time of just 15 months. Both inherited and acquired genetic variation influence gliomagenesis. Previous genome-wide association studies (GWAS) have discovered seven glioma risk loci, including two in genes involved in telomere structure and function (TERT and RTEL1). METHODS: To identify novel high-grade glioma risk loci, we performed SNP imputation and meta-analysis of genome-wide array data from The University of California, San Francisco Adult Glioma Study (AGS), The Cancer Genome Atlas (TCGA) and the Wellcome Trust Case-Control Consortium (WTCCC) (1,013 cases and 6,595 controls). SNPs with P < 1.0x10-6 in the discovery meta-analysis underwent attempted replication in an additional 631 glioblastoma cases and 1141 controls from The Mayo Clinic and UCSF. To investigate potential functional mechanisms through which SNPs might promote gliomagenesis, we examined the relationship between mean leukocyte telomere length (LTL) and glioma risk loci using data from a recent GWAS of LTL (N = 37,684). RESULTS: One novel SNP association from the discovery phase meta-analysis met criteria for attempted replication. This SNP was significantly associated with high-grade glioma risk in the replication dataset (P = 3.4x10-3). The combined P-value for all 1644 cases and 7736 controls achieved genome-wide statistical significance (8.3x10-9). Glioma risk alleles in both our newly identified risk region and the known TERT risk locus were strongly associated with longer LTL (P < 5.0x10-8). In contrast, glioma risk alleles near RTEL1 were inconsistently associated with LTL and suggested the presence of distinct causal alleles underlying these two phenotypes. No other established glioma risk loci were associated with LTL. CONCLUSIONS: We identify a novel genome-wide significant association between a constitutive SNP and glioma risk. Because telomere maintenance is a universal requirement of oncogenic progression and telomere length displays substantial interindividual variability, telomere length is a promising epidemiologic risk factor for human cancers. We demonstrate that alleles in our novel locus and in TERT are associated with both longer mean LTL and with increased glioma risk. These results strongly implicate inherited variation near these two genes in facilitating gliomagenesis through a mechanism involving lengthened telomeres. SECONDARY CATEGORY: n/a.
Simplified protocol for focal radiofrequency ablation using the HALO90 device: short-term efficacy and safety in patients with dysplastic Barrett’s esophagus
Authors: Hannah Künzli, Dirk Schölvinck, K. Phoa, Erik Schoon, Martin Houben, Jacques Bergman, Bas Weusten
Journal: Endoscopy (2015)

The standard protocol for focal radiofrequency ablation (RFA) of Barrett's esophagus comprises two applications of radiofrequency energy, cleaning of the ablated areas and catheter, and two further applications (2 × 15 J/cm(2) - cleaning - 2 × 15 J/cm(2)). A simplified protocol (3 × 15 J/cm(2), no cleaning) proved noninferior to standard protocol for individual islands of Barrett's esophagus, but may be associated with higher stenosis rates when applied circumferentially and sequentially over time. We evaluated the efficacy and safety of the above mentioned simplified protocol.Barrett's esophagus patients undergoing focal RFA using the simplified protocol in four tertiary referral centers were retrospectively included. During each focal ablation, the gastroesophageal junction (GEJ) was ablated circumferentially in addition to Barrett's esophagus islands or tongues. Sessions continued at 8 to 12-week intervals until complete resolution of Barrett's esophagus. Primary outcome parameters comprised complete remission of dysplasia and of intestinal metaplasia, and stenosis requiring dilation.83 patients with dysplastic Barrett's esophagus (median Prague classification C1M3) were enrolled; 66/83 (80 %) had endoscopic resection of a visible lesion before RFA. Intention-to-treat analysis showed complete remission of dysplasia in 78/83 (94 %) and of intestinal metaplasia in 72/83 (87 %). Stenosis requiring dilation developed in 9/83 (11 %), necessitating a median 2 dilation sessions (range 1 - 9), with ≥ 8 sessions in three patients.A treatment algorithm incorporating the simplified protocol of 3 × 15 J/cm(2), with no cleaning, for all focal RFA sessions, appears effective. The associated number and severity of stenoses, however, raises safety concerns.