tbuckley/cabot-search huggingface dataset:
Abstract 13996: Does Copeptin Provide Additional Risk Stratification in Chest Pain Patients With a Mild Troponin Elevation?
Authors: Nicholas Marston, Kevin Shah, Christian Mueller, Sean Xavier-Neath, Robert Christenson, Jim McCord, Richard Nowak, Gary Vilke, Lori Daniels, Judd Hollander, Fred Apple, Chad Cannon, John Nagurney, Donald Schreiber, Christopher deFilippi, Chris Hogan, Deborah Diercks, Alexander Limkakeng, Inder Anand, Alan Wu, Paul Clopton, Allan Jaffe, Frank Peacock, Alan Maisel
Journal: Circulation (2014)

Introduction: Copeptin has demonstrated a role in early rule out for acute myocardial infarction in combination with a negative troponin. However, the value of copeptin in patients with a positive troponin is not established. Hypothesis: The addition of a baseline copeptin at chest pain presentation will improve risk stratification in patients with mild troponin elevation. Methods: The multi-center CHOPIN trial enrolled 2071 acute chest pain patients. All subjects with ST segment elevations were excluded from this analysis. Of the remaining patients, 124 had a mildly elevated troponin (defined by &lt; 2x URL) and were included in the study cohort. Baseline cTnI and copeptin levels were drawn on presentation, and another cTnI at 2 hours. Copeptin ≤14 pmol/l and troponin deltas ≤10% from baseline were considered positive. Two independent blinded cardiologists adjudicated AMI diagnosis. The value of a baseline copeptin in this cohort was assessed using AMI incidence, odds ratio, sensitivity, and negative predictive value (NPV). Results: Of the 124 patients in the study cohort, 73 (59%) had an elevated copeptin and an associated AMI incidence of 25% (18 AMIs). The remaining 51 patients (41%) were copeptin negative and diagnosed with 3 AMIs, an incidence of 5.9% (p = 0.006, figure 1). A positive copeptin increased the likelihood of AMI diagnosis with an odds ratio of 5.3 (95% CI: 1.5-19.2). The sensitivity and NPV for AMI were 86% and 94%, both of which were higher than the delta troponin (table 1). When an initial copeptin was combined with the delta troponin the sensitivity and NPV for AMI improved to 100%. Conclusion: Use of copeptin in chest pain patients with mild troponin elevation provides further risk stratification. The combination of copeptin with a delta troponin may aid in earlier AMI rule out in this subset of patients. This approach could be especially relevant as the increasing use of high sensitivity troponin assays leads to greater rates of mild troponin elevations.
Abstract 16571: Temporal Release Pattern of Copeptin and Troponin in Patients With Suspected ACS and Spontaneous Acute Myocardial Infarction
Authors: Anna Slagman, Julia Searle, Fabian Holert, Christian Müller, Martin Möckel
Journal: Circulation (2014)

Introduction: Copeptin, a surrogate marker for vasopressin has been shown to have potential for the early rule-out of acute myocardial infarction in combination with cardiac troponin. The temporal release pattern of copeptin in spontaneous AMI has not been investigated until now at more than three time-points. Objective: To investigate the temporal release pattern of copeptin and cardiac troponin in spontaneous acute myocardial infarction at six time-points from ambulance until 12-36 hours. Methods: Patients with suspected ACS and acute symptom onset were enrolled in this study. Blood samples were collected on the ambulance, at admission and after 2, 4, 6 and 12-36 hours. Gold-Standard diagnoses were adjudicated according to the third definition of myocardial infarction by a cardiologist. Copeptin (BRAHMS Kryptor Copeptin us) and troponin T (Roche Diagnostics, Elecsys) were measured in heparin plasma. Results: Overall 93 patients were enrolled. The most frequent diagnosis was STEMI (n=37, 39.8%), 20 patients were diagnosed with NSTEMI (21.5%), 20 patients had UAP (21.5%) and 16 patients were diagnosed with other, non-ACS diagnoses (17.2%). The release kinetic of copeptin differed between different diagnoses: patients with AMI had significantly higher values at admission as compared to patients with UAP and other diagnoses (figure 1 A). Troponin values on the ambulance were low in all patients but increased over time in patients with STEMI and NSTEMI (figure 1B). Conclusions: In early presenters with ACS copeptin and troponin show typical temporal release pattern; the very early rise and decrease within 12-36h of copeptin in spontaneous AMI has been shown for the first time. The pathophysiological stimulus for the copeptin-release in spontaneous AMI should be further investigated.
Positional cloning of the gene for X-linked retinitis pigmentosa 2
Authors: Uwe Schwahn, Steffen Lenzner, Juan Dong, Silke Feil, Bernd Hinzmann, Gerard van Duijnhoven, Renate Kirschner, Myriam Hemberger, Arthur A.B. Bergen, Thomas Rosenberg, Alfred J.L.G. Pinckers, Reinald Fundele, André Rosenthal, Frans P.M. Cremers, H.-Hilger Ropers, Wolfgang Berger
Journal: Nature Genetics (1998)
Abstract P2-03-18: Discovery of novel amplified genes in primary breast cancer with copy number and gene expression analysis of whole exome and transcriptome sequencing data
Authors: Eunshin Lee, Woosung Lim, Kyung-Min Lee, Tae-kyung Yoo, Jongjin Kim, Han-Byoel Lee, Yun-Gyoung Kim, YoungJoon Kang, Min Kyoon Kim, Hyeong-Gon Moon, Dong-Young Noh, Wonshik Han Han
Journal: Cancer Research (2015)

Abstract Introduction: Copy number alteration of genome is common in breast cancer and tend to have more driver role than single point mutations. Traditionally, genome-wide analysis of DNA copy number changes were done by array CGH or SNP array method. Here, we did DNA whole exome sequencing (WES) and RNA-seq using Next Generation Sequencing (NGS) technology to find common genes or chromosomal regions of which DNA copy was highly amplified and at the same time RNA expression was also upregulated. Materials and Method: RNA and DNA were extracted fromfresh frozen tissues of 93 breast cancer patients. WES and RNA-seq were done using NGS technology (Illumina HiSeq 2000). As a control, normal DNA from all matched patients were also sequenced. GATK was used to gain mean depth and coverage data for targeted regions.CNVs were calculated with ExomeCNV, a statistical method to detect somatic CNVs using depth-of-coverage information from mapped short sequence reads.To estimate expression levels, the relative transcript abundances were measured in FPKM using Cufflinks. Results and Discussion: DNA of 1,737 genes were highly amplified (log R&amp;gt;1.0) in two or more samples. The two most commonly amplified chromosomes were chromosome 8 and 17. We applied a cut-off for higher gene expression as relative FPKM &amp;gt;1.5. ERBB2 amplifications and high expression were most common (21.5%) of all genes and it was in agreement withHER-2 IHC and FISH result. Among previously reported amplified genes, FGFR1 (5.4%) and PVT1 (8.6%) in chromosome 8, CCND1, PAK1 (3.2%) and EMSY (4.3%) in chromosome 11, CCNE1 (4.3%) in chromosome 19 were also identified in this study. IGF1R high amplification and expression was found in two samples, and ESR1, MDM2, KIT was found in only one sample each. We found uncommon but novel and recurrent highly amplified and expressed genes: CLK4 in 5q (3.2%), AHI/MYB in 6q (3.2%), MMP7(2.2%) andMALAT1 in 11q (1.1%), and NEK8 in 17q (4.3%) We designed FISH probe for this 5 new genes and confirmed the high amplifications in each sample with FISH. Functional study of these genes will be followed for the driver role of these genes in carcinogenesis and progression of breast cancer cells. Citation Format: Eunshin Lee, Woosung Lim, Kyung-Min Lee, Tae-kyung Yoo, Jongjin Kim, Han-Byoel Lee, Yun-Gyoung Kim, YoungJoon Kang, Min Kyoon Kim, Hyeong-Gon Moon, Dong-Young Noh, Wonshik Han Han. Discovery of novel amplified genes in primary breast cancer with copy number and gene expression analysis of whole exome and transcriptome sequencing data [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-03-18.
Is the aminoterminal propeptide of type III procollagen degraded in the liver?
Authors: Kirsten D. Bentsen, Steen Boesby, Preben Kirkegaard, Carsten Paln˦s Hansen, Steen Lindk˦r Jensen, Kim Hørslev-Petersen, Ib Lorenzen
Journal: Journal of Hepatology (1988)
Chronic lymphocytic leukemia: 2015 Update on diagnosis, risk stratification, and treatment
Authors: Michael Hallek
Journal: American Journal of Hematology (2015)

Disease overview : Chronic lymphocytic leukemia (CLL) is the commonest leukemia in western countries. The disease typically occurs in elderly patients and has a highly variable clinical course. Leukemic transformation is initiated by specific genomic alterations that impair apoptosis of clonal B‐cells. Diagnosis : The diagnosis is established by blood counts, blood smears, and immunophenotyping of circulating B‐lymphocytes, which identify a clonal B‐cell population carrying the CD5 antigen as well as B‐cell markers. Prognosis : Two prognostic staging systems exist, the Rai and Binet staging systems, which are established by physical examination and blood counts. Various biological and genetic markers also have prognostic value. Deletions of the short arm of chromosome 17 ( del(17p) ) predict resistance to available chemotherapies. Comprehensive prognostic scores are currently being developed. Therapy : Patients with active or symptomatic disease or with advanced Binet or Rai stages require therapy. For physical fit patients, chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab remains the current standard therapy. For unfit patients, treatment with an anti‐CD20 antibody (obinutuzumab or rituximab or ofatumumab) plus a milder chemotherapy (Chlorambucil) may be applied. At relapse, the initial treatment may be repeated, if the treatment‐free interval exceeds two to three years. If the disease relapses earlier, therapy should be changed using alternative agents such as bendamustine (plus rituximab), alemtuzumab, lenalidomide, ofatumumab, ibrutinib, or idelalisib. Patients with a del(17p) or TP53 mutation can be treated with ibrutinib or a combination of idelalisib and rituximab. An allogeneic SCT may be considered in relapsing patients with TP53 mutations or del(17p) or patients that are refractory to repeated chemoimmunotherapies. Future challenges : Several new agents (e.g., ibrutinib, idelalisib, obinutuzumab) hold the potential to improve the outcome of patients with CLL. However, their optimal use (in terms of combination, sequence, and duration) is unknown. Therefore, CLL patients should be treated in clinical trials whenever possible.Am. J. Hematol. 90:447–460, 2015. © 2015 Wiley Periodicals, Inc.
Abstract 146: Combining molecular targeted drugs to inhibit both cancer cells and activated stromal cells in colon cancer
Authors: Ryo Yuge, Yasuhiko Kitadai, Kei Shinagawa, Mieko Onoyama, Yuichiro Tanaka, Shinji Tanaka, Wataru Yasui, Kazuaki Chayama
Journal: Cancer Research (2014)

Abstract Recent studies have shown that tumor growth and metastasis are not determined by cancer cells alone but also by a variety of stromal cells. We have shown previously that platelet-derived growth factor receptors (PDGF-Rs) are overexpressed by various stromal cell populations, but not by cancer cells themselves in human colon cancer tissues. Blockade of PDGF-R signaling pathways in tumor-associated stromal cells has been shown to inhibit the stromal reaction. Activation of phosphoinositide 3-kinase (PI3K)/Akt/ mammalian target of rapamycin (mTOR) signaling is frequently observed in many cancer types and has been implicated in the pathogenesis of various diseases. mTOR is a central regulatory kinase that increases the production of proteins that stimulate key cellular processes such as cell proliferation, metabolism, survival, and angiogenesis. However, the effects of mTOR inhibitors on the stromal component of tumor tissues have not been studied. In the present study, the effects of nilotinib (PDGF-R tyrosine kinase inhibitor) and everolimus (mTOR inhibitor) on tumor development and metastasis, were examined using orthotopic and experimental liver metastatic models of human colon cancer, whereby KM12SM cells were implanted into the cecum and spleen of nude mice, respectively. Groups of mice received saline (control), nilotinib (100mg/kg/day) or everolimus (1mg/kg/day), or a combination of nilotinib (100mg/kg/day) and everolimus (1mg/kg/day) by daily oral gavage. After 4 weeks of treatment, primary tumors and metastatic lesions were resected, and specimens were analyzed histologically and immunohistochemically for comparison between the treatment group and control group. After treatment with nilotinib, the stromal reaction was significantly decreased. After treatment with everolimus, the stromal reaction was not decreased, but tumor cell proliferation and microvessel density were decreased. With the combination therapy, both tumor cell proliferation and the stromal reaction were decreased and apoptosis of tumor cells was increased, resulting in a remarkable decrease in tumor size and the number of metastatic liver lesions. Therefore, concurrent inhibition of tumor cells and activated stromal cells by combination therapy may represent a novel molecular-targeted approach for patients with colon cancer. Citation Format: Ryo Yuge, Yasuhiko Kitadai, Kei Shinagawa, Mieko Onoyama, Yuichiro Tanaka, Shinji Tanaka, Wataru Yasui, Kazuaki Chayama. Combining molecular targeted drugs to inhibit both cancer cells and activated stromal cells in colon cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 146. doi:10.1158/1538-7445.AM2014-146
Development of Plasma-Cell Neoplasms in BALB/c Mice After Intraperitoneal Injection of Paraffin-Oil Adjuvant, Heat-Killed Staphylococcus Mixtures
Authors: Michael Potter, Charlotte L. Robertson
Journal: JNCI Journal of the National Cancer Institute (1960)

Plasma-cell neoplasms developed in 7 of 64 mice inoculated intraperitoneally with an emulsion of incomplete Freund's adjuvant and heat-killed staphylococci. Thirty-two mice received only the injection; 4 plasma-cell neoplasms developed in this group. The remaining 32 mice received in addition to the injection a series of skin paintings with methylcholanthrene; 3 plasma-cell neoplasms developed in this group. All the other methylcholanthrene-painted mice developed carcinomas of the skin. Four of the 7 plasma-cell neoplasms were successfully transplanted. Mice with transplants developed serum myeloma globulins similar to those found in the original mouse. The role of the paraffin-oil staphylococcal emulsion in the production of the plasma-cell neoplasms was not definitely established. This point is briefly discussed.
House dust mite-induced histamine release from washed blood cells.
Authors: H. Mosbech, P. Stahl Skov
Journal: Allergy (1987)

In a selected group of 60 house dust mite allergic asthmatics, the correlation between the bronchial sensitivity to house dust mite and effect parameters of mite‐induced histamine release from washed blood cells was evaluated. Using a sensitive glass microfibre‐based method, a significant positive correlation (r = 0.60; P &lt; 0.001) was found between bronchial allergen sensitivity and basophil cell sensitivity expressed as the house dust mite concentration necessary to give half the maximum histamine release. No correlation was found between bronchial sensitivity and other parameters of the histamine release response. This way of determining the histamine release from washed blood cells is a simple and valuable alternative to bronchial allergen challenge.
Selective targeting of IRF4 by synthetic microRNA-125b-5p mimics induces anti-multiple myeloma activity in vitro and in vivo
Authors: E Morelli, E Leone, M E Gallo Cantafio, M T Di Martino, N Amodio, L Biamonte, A Gullà, U Foresta, M R Pitari, C Botta, M Rossi, A Neri, N C Munshi, K C Anderson, P Tagliaferri, P Tassone
Journal: Leukemia (2015)

Interferon regulatory factor 4 (IRF4) is an attractive therapeutic target in multiple myeloma (MM). We here report that expression of IRF4 mRNA inversely correlates with microRNA (miR)-125b in MM patients. Moreover, we provide evidence that miR-125b is downregulated in TC2/3 molecular MM subgroups and in established cell lines. Importantly, constitutive expression of miR-125b-5p by lentiviral vectors or transfection with synthetic mimics impaired growth and survival of MM cells and overcame the protective role of bone marrow stromal cells in vitro. Apoptotic and autophagy-associated cell death were triggered in MM cells on miR-125b-5p ectopic expression. Importantly, we found that the anti-MM activity of miR-125b-5p was mediated via direct downregulation of IRF4 and its downstream effector BLIMP-1. Moreover, inhibition of IRF4 translated into downregulation of c-Myc, caspase-10 and cFlip, relevant IRF4-downstream effectors. Finally, in vivo intra-tumor or systemic delivery of formulated miR-125b-5p mimics against human MM xenografts in severe combined immunodeficient/non-obese diabetic mice induced significant anti-tumor activity and prolonged survival. Taken together, our findings provide evidence that miR-125b, differently from other hematologic malignancies, has tumor-suppressor activity in MM. Furthermore, our data provide proof-of-concept that synthetic miR-125b-5p mimics are promising anti-MM agents to be validated in early clinical trials.
Abstract 20267: Diminished Levels of Circulating Bone Morphogenetic Protein 9 Identify Pulmonary Arterial Hypertension Associated With Liver Disease
Authors: Ivana Nikolic, Samuel D Paskin-Flerlage, Rajeev Malhotra, Lai-Ming Yung, Raymond T Chung, Richard N Channick, Kari E Roberts, Paul B Yu
Journal: Circulation (2014)

Background: Dysregulated bone morphogenetic protein (BMP) signaling is thought to contribute to the pathogenesis of pulmonary arterial hypertension (PAH). BMP9 can be detected in the circulation at physiologically active concentrations, and is thought to serve as a vascular endothelial quiescence factor. Aim: We hypothesized that circulating levels of BMP9 might be associated with altered endothelial homeostasis, and could help predict the presence of PAH or distinguish between PAH of distinct etiologies. Methods: Circulating levels of BMP9, and its biological inhibitor, soluble Endoglin (sEng), were measured in the plasma of 96 patients with various etiologies of pulmonary hypertension and 28 healthy individuals using enzyme-linked immunoassays. Results: Patients with Group I PAH (n=44) had significantly lower levels of BMP9 compared to healthy individuals (188 ± 22 pg/mL vs 254 ± 17 pg/mL, mean ± SEM, p=0.001). BMP9 was significantly decreased in PAH associated with connective tissue disease (p=0.02), but was most profoundly decreased in patients with portopulmonary hypertension (82 ± 27 pg/mL, p&lt;0.0001 vs controls). BMP9 was a strong predictor of concomitant liver disease (ROC AUC=0.920), correlating positively with serum albumin and platelet counts, and negatively with INR, total bilirubin, cardiac index and MELD score among Group I PAH patients (
Prevention and Reversal of Type 1 Diabetes—Past Challenges and Future Opportunities
Authors: Jay S. Skyler
Journal: Diabetes Care (2015)

Over the past three decades there have been a number of clinical trials directed at interdicting the type 1 diabetes (T1D) disease process in an attempt to prevent the development of the disease in those at increased risk or to stabilize-potentially even reverse-the disease in people with T1D, usually of recent onset. Unfortunately, to date there has been no prevention trial that has resulted in delay or prevention of T1D. And, trials in people with T1D have had mixed results with some showing promise with at least transient improvement in β-cell function compared with randomized control groups, while others have failed to slow the decline in β-cell function when compared with placebo. This Perspective will assess the past and present challenges in this effort and provide an outline for potential future opportunities.
Abstract B20: Design, synthesis and SAR studies of novel survivin inhibitors with potent antiproliferative properties
Authors: Min Xiao, Jin Wang, Yan Lu, Duane D. Miller, Wei Li
Journal: Cancer Research (2015)

Abstract A series of novel survivin inhibitors were designed and synthesized based our recently reported compound UC-112. All the new analogs were tested against several cancer cell lines including multidrug-resistant melanoma cancer cell lines. The in vitro results showed that several compounds had excellent antiproliferative activity with IC50 values within nanomolar range. Mechanism of action of those new analogs was investigated by Western blot assay. The study confirmed that the new analogs acted by selectively suppressing survivin with the similar mechanism as the parent compound UC-112. Those new analogs represent promising agents that can be further developed for selective anticancer treatment. Citation Format: Min Xiao, Jin Wang, Yan Lu, Duane D. Miller, Wei Li. Design, synthesis and SAR studies of novel survivin inhibitors with potent antiproliferative properties. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Melanoma: From Biology to Therapy; Sep 20-23, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(14 Suppl):Abstract nr B20.
Abstract 13604: Integrated Area of Desaturation Index can Predict Three-Year Prognosis in Heart Failure Patients after Adaptive Servo Ventilation Therapy
Authors: Noriaki Takama, Hiroshi Hasegawa, Keita Goto, Kuniko Masuda, Hidemi Sorimachi, Makito Sato, Masaru Obokata, Yae Matsuo, Hirokazu Sano, Ryuichi Funada, Syu Kasama, Norimichi Koitabashi, Masahiko Kurabayashi
Journal: Circulation (2014)

Introduction: Adaptive servo ventilation (ASV) is used as a device for patients with heart failure. Previously, we reported that Integrated Area of Desaturation Index (IAD index) can estimate the efficacy of ASV therapy in acute phase. However, it is unclear that IAD index can estimate long-term prognosis after ASV therapy. Hypothesis: We hypothesize that IAD index can predict long-term prognosis after ASV therapy. Methods: The study group consisted of 57 HF patients. The mean age was 70 ± 11 years. After treating the underlying disease in the acute phase, patients were treated with ASV. To estimate short-term effects, we established the association between changes in brain natriuretic peptide ([[Unable to Display Character: ⊿]]BNP) and left ventricular ejection fraction ([[Unable to Display Character: ⊿]]LVEF). We also estimate several polysomnographic parameters including IAD index, which is new measurement for assessing the severity of sleep apnea, which is obtained by integrating nocturnal...