tbuckley/cabot-search huggingface dataset:
Protocol 06PRT/7719: A study to the impact of nutrition on children with ADHD (INCA study): a Dutch randomised controlled trial into the effects of food on the behaviour of a random group of school-going children meeting the DSM-IV criteria for ADHD, including immunological testing
Authors: L. Pelsser, H.F.J. Savelkoul, J. Buitelaar
Journal: The Lancet (2007)
High EVI1 Expression Predicts Outcome in Younger Adult (15 to 60 years) Patients with Acute Myeloid Leukemia and Is Associated with Distinctive Cytogenetic Subgroups.
Authors: Gröschel Stefan, Sanne Lugthart, Richard Schlenk, Peter Valk, Karina Eiwen, Chantal Goudswaard, Willem JL Van Putten, Sabine Kayser, Leo Verdonck, Michael Lübbert, Gert Ossenkoppele, Ulrich Germing, Ingo Schmidt-Wolf, Jürgen Krauter, Arnold Ganser, Hartmut Döhner, Bob Löwenberg, Konstanze Döhner, Ruud Delwel
Journal: Blood (2009)
DNA Double-Strand Break Formation Induced by Replication Arrest Depend On Artemis.
Authors: Masatoshi Takagi, Junya Unno, Thoru Kiyono, Fumiko Honda, Hirobumi Teraoka, Daisuke Maeda, Mitsuko Masutani, Tomohiro Morio, Shuki Mizutani
Journal: Blood (2009)
Precision oncology: the UC San Diego Moores Cancer Center PREDICT experience.
Authors: Barbara A. Parker, Maria Clemence Schwaederle, Richard B. Schwab, Gregory A. Daniels, David Eric Piccioni, Teresa L. Helsten, Lyudmila Bazhenova, Paul T. Fanta, Scott Michael Lippman, Razelle Kurzrock
Journal: Journal of Clinical Oncology (2015)

11103 Background: By profiling their patients’ tumors, oncologists now have the option to use molecular results to match patients with drug(s) based on specific biomarkers. Methods: In this observational study, clinical outcomes of 348 patients with solid advanced cancers who had next-generation sequencing (NGS, 182 or 236 genes) performed were analyzed under the PREDICT (Profile Related Evidence Determining Individualized Cancer Therapy) study protocol. Progression-free survival (PFS) and responses were recorded for patients that received a matched therapy. Results: Of 348 patients analyzed, 47 (13.5%) were treated with a matched therapy after NGS results. Two additional patients were matched but were lost to follow up. Thirty-four percent of patients (16/47) achieved stable disease (SD) > 6months (n = 7)/complete response (CR, n = 0)/partial response (PR, n = 9). The median PFS for the matched patients was 4.0 months (N = 47, range, 0.5 to 22.3 months). The median PFS was 9.5 months (range, 3.4 to 22.3 months) for the 16 patients with SD > 6 months/CR/PR. The median PFS (PFS2) of the patients given matched therapies was longer than the median PFS (PFS1) of the available prior therapies (PFS1; N = 38 available; P = 0.038). There was no difference between the median PFS when the matched drug targeted the alteration “directly” (agent impacts the molecular alteration or its immediate downstream effector) versus “indirectly” ( > 1 effector removed from the alteration) (N = 32 vs 15 patients; PFS = 3 vs 4 months; P = 0.74); if we defined direct matches as including only drugs targeting the alteration itself, and indirect matches when the alteration was > 1 effector removed, the differences in PFS remained insignificant. Conclusions: Patients with advanced cancers treated with a biomarker-based approach (matched therapy) achieved a 34% rate of SD > 6 months/CR/PR and had a significantly longer median PFS than that for the available last prior therapies. Although the numbers are small, there were no differences in PFS between patients who received therapy that was directly versus indirectly matched to their alteration(s).
Zoledronic Acid Is an Effective Treatment for Osteoporosis in Patients with Thalassemia Major: Results of a Randomized, Placebo-Controlled, Trial.
Authors: Ersi Voskaridou, Dimitris Loukopoulos, Eleni Stoupa, Eugenia Spyropoulou, John Meletis, Evangelos Terpos
Journal: Blood (2005)
Case 19-1977
Authors: Richard C. Cabot, Robert E. Scully, James J. Galdabini, Betty U. McNeely, Charles A. Hales, Eugene J. Mark
Journal: New England Journal of Medicine (1977)

Presentation of Case First admission. A 56-year-old woman was admitted to the hospital because of pneumonia.She was well until three months previously, when a chronic nasal dryness became more severe. An x-ray film of the chest was normal except for calcification at the apex of the right lung. On the advice of a physician she began to use mineral-oil nose drops 10 to 20 times daily; they were instilled in the supine position, followed by deep inhalations. Two and a half months before entry fever developed, accompanied by shaking chills, but there was no cough, sputum production or . . .
Nogo‐B receptor deficiency increases liver X receptor alpha nuclear translocation and hepatic lipogenesis through an adenosine monophosphate–activated protein kinase alpha–dependent pathway
Authors: Wenquan Hu, Wenwen Zhang, Yuanli Chen, Ujala Rana, Ru‐jeng Teng, Yajun Duan, Zhong Liu, Baofeng Zhao, Jamie Foeckler, Hartmut Weiler, Rachel E. Kallinger, Michael J. Thomas, Kezhong Zhang, Jihong Han, Qing Robert Miao
Journal: Hepatology (2016)

Nogo‐B receptor (NgBR) was identified as a specific receptor for binding Nogo‐B and is essential for the stability of Niemann‐Pick type C2 protein (NPC2) and NPC2‐dependent cholesterol trafficking. Here, we report that NgBR expression levels decrease in the fatty liver and that NgBR plays previously unrecognized roles in regulating hepatic lipogenesis through NPC2‐independent pathways. To further elucidate the pathophysiological role of NgBR in mammals, we generated NgBR liver‐specific knockout mice and investigated the roles of NgBR in hepatic lipid homeostasis. The results showed that NgBR knockout in mouse liver did not decrease NPC2 levels or increase NPC2‐dependent intracellular cholesterol levels. However, NgBR deficiency still resulted in remarkable cellular lipid accumulation that was associated with increased free fatty acids and triglycerides in hepatocytes in vitro and in mouse livers in vivo . Mechanistically, NgBR deficiency specifically promotes the nuclear translocation of the liver X receptor alpha (LXRα) and increases the expression of LXRα‐targeted lipogenic genes. LXRα knockout attenuates the accumulation of free fatty acids and triglycerides caused by NgBR deficiency. In addition, we elucidated the mechanisms by which NgBR bridges the adenosine monophosphate–activated protein kinase alpha signaling pathway with LXRα nuclear translocation and LXRα‐mediated lipogenesis. Conclusion : NgBR is a specific negative regulator for LXRα‐dependent hepatic lipogenesis. Loss of NgBR may be a potential trigger for inducing hepatic steatosis. (H epatology 2016;64:1559‐1576)
Unusual Manifestations of Acute Leukemia
Authors: Christian Blank, Harald M. Wagner, Ulrich Hohenleutner, Reinhard Andreesen
Journal: Journal of Clinical Oncology (2000)

Article Tools Unusual Manifestations of Acute Leukemia Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2000.18.19.3437 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11013285 Unusual Manifestations of Acute Leukemia Christian BlankxChristian BlankSearch for articles by this author , Harald M. WagnerxHarald M. WagnerSearch for articles by this author , Ulrich HohenleutnerxUlrich HohenleutnerSearch for articles by this author , Reinhard AndreesenxReinhard AndreesenSearch for articles by this author Show More Klinikum der Universität Regensburg, Regensburg, Germany https://doi.org/10.1200/JCO.2000.18.19.3437 First Page Full Text PDF Figures and Tables © 2000 by American Society of Clinical Oncology
356TiP Phase III clinical trials of atezolizumab in combination with chemotherapy in chemotherapy-naive patients with advanced NSCLC
Authors: T.S.K. Mok, F. Cappuzzo, R.M. Jotte, M. Reck, V. Papadimitrakopoulou, A. Sandler, D. Waterkamp, W. Verret, Y. Shen, M.A. Socinski
Journal: Annals of Oncology (2015)
The difficult diagnosis of pulmonary vascular disease in heart failure
Authors: Robert Naeije, Anna Ryan Hemnes
Journal: European Respiratory Journal (2016)

In this issue of the European Respiratory Journal ( ERJ ), Gerges et al. [1] propose an interesting refinement of the diagnosis of pulmonary vascular disease in patients with left heart failure. The problem is of importance. Left heart disease with increased pulmonary venous pressure, abbreviated as LHD in recent reviews and guidelines, is by far the most common cause of pulmonary hypertension (PH) [2–4]. Furthermore, up to 80% of patients with heart failure with preserved or reduced ejection fraction and/or mitral or aortic valve diseases are exposed to the eventual development of PH with associated worsened symptomology and decreased survival [2–4]. A step forward in the diagnosis of pulmonary vascular disease in patients with left heart failure <http://ow.ly/kR47300mzcf>
OT-101: An anti-TGF-beta-2 antisense- primed tumors to subsequent chemotherapies.
Authors: Larn Hwang, Kevin Ng, Wen Wang, Vuong N. Trieu
Journal: Journal of Clinical Oncology (2016)

e15727 Background: Overexpression of transforming growth factor-beta 2 (TGF-b2) is associated with poor prognosis and plays a key role for malignant progression of various tumors by inducing proliferation, metastasis, angiogenesis and immunosuppression. Methods: A total of 37 patients with advance pancreatic cancer were treated with Trabedersen (OT-101) by intravenous infusion in escalating doses of 2 treatment schedules (initial schedule: 7-days on, 7-days off; modified schedule: 4-days on, 10-days off; two cycles as core study and up to 10 cycles for expanded study). Results: MTD for 7/7 regimen (N = 11) was 160 mg/m2/d; whereas MTD was not reached on 4/10 regimen (N = 27) even at highest dose of 330 mg/m2/d. There was 16 2nd line patients and 11 3rd line and beyond on 4/10 regimen. The PFS/OS of these 2nd line patients in months were: 1.87/5.60 (N = 6), 1.87/9.93 (N = 11) and 2.72/11.80 (N = 5) at increasing mean dose of 140, 167, and 196, respectively. The OS of 9.93 and 11.80 are higher than the highest reported in the 65 trials reported in the literature during 1997-2015 (range = 2.50-9.20/median = 5.50). The corresponding PFS values were in line with reported literarure (range = 0.00-7.65/median = 2.43). The OS of this 4/10 cohort treated with subsequent chemotherapies was 14.7 and 2.93 mos with and without subsequent chemotherapies, p = 0.0023. Chemotherapy on 2ndline followed with subsequent Trabedersen 4/10 regimen as third line was ineffective with OS of 2.80 mos (N = 9) versus 9.93 mos (N = 11), p = 0.046. Conclusions: Trabedersen (OT-101) treatment was characterized by outstanding OS which was not supported by PFS. The effect was seen primarily when chemotherapies were used as third line after Trabedersen treatment; OS benefit was not observed for the converse- chemotherapies used first followed by Trabedersen. The data support the enhancement of subsequent chemotherapies following Trabedersen treatment suggesting a combination trial of Trabedersen and chemotherapies with sequencing. Clinical trial information: NCT00844064.
Abstract 4424: Acetylation of Fascin on the lysine 471 residue produces a change in growth and mobility phenotype of esophageal cancer cells by inducing F-actin rearrangement
Authors: Fa-Min Zeng, Xiao-Ning Wang, Ying-Li Zhang, Lian-Di Liao, En-Min Li, Li-Yan Xu
Journal: Cancer Research (2016)

Abstract Elevated expressions of fascin mRNA and protein in cancer cells have been correlated with aggressive clinical course, poor prognosis and shorter survival. Fascin is an evolutionarily conserved actin-binding protein that plays a key role in forming filopodia. It is reported that the lysine 471 residue (K471) of fascin can be acetylated and also involves in its actin binding, but the roles of K471 acetylation in filopodia formation are still uncertain. In this paper, we produced point mutants mimicking the active deacetylated (Lys471Arg, K471R) or inactive acetylated (Lys471Gln, K471Q) states of fascin. The actin-binding assay showed that the fascin K471Q mutation decreased the actin binding activity of fascin, compared with wild-type fascin (WT) and K471R mutant fascin in the esophageal cancer cells. Moreover, live imaging revealed that K471Q mutant fascin reduced the number and length of filopodia, whereas the K471R mutant increased filopodia frequency. The fascin K471Q mutation changed the straight filopodia became forniciform filopodia. The protrusion presented abnormal morphology when cells spread. Further functional experiments showed that the K471Q mutant fascin rendered the tumor cell migration, invasion and tumorigenesis decrease significantly, whereas K471R mutant fascin like WT fascin still maintained a strong ability. Taken together, we propose that the lysine K471 residue may be a key specific actin crosslinking site and also involved in the tumor biological function of fascin. Citation Format: Fa-Min Zeng, Xiao-Ning Wang, Ying-Li Zhang, Lian-Di Liao, En-Min Li, Li-Yan Xu. Acetylation of Fascin on the lysine 471 residue produces a change in growth and mobility phenotype of esophageal cancer cells by inducing F-actin rearrangement. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4424.
Abstract 991: Long non-coding RNA LINC01133 inhibits epithelial-mesenchymal transition and metastasis in colorectal cancer by interacting with SRSF6
Authors: Jianlu Kong, Honghe Zhang, Enping Xu, Qiong Huang, Jian Chen, Maode Lai
Journal: Cancer Research (2016)

Abstract Objective Long non-coding RNAs (lncRNAs) play crucial roles in many biological and pathological processes, including tumor metastasis. The aim of this study was to investigate the expression and molecular function of LINC01133 in colorectal cancer (CRC). Design LINC01133 expression was assessed in CRC cell lines and 219 clinical tissue samples by quantitative RT-PCR. Small interfering RNA-mediated knockdown was used to probe the biological functions of LINC01133, and its binding protein was isolated and identified using ChIRP-MS combined with western blot, and further validated by RNA immunoprecipitation assays. Results We found that LINC01133 inhibited CRC cell migration and invasion by regulating the epithelial-mesenchymal transition (EMT), and was downregulated by TGF-β. We then showed that SRSF6 directly bound to LINC01133. Furthermore, we confirmed that that the EMT process regulated by LINC01133 in CRC cells depended on the presence of SRSF6. The expression of LINC01133 was markedly downregulated in CRC tissues relative to their corresponding normal mucosal tissues, and patients with tumors displaying higher LINC01133 expression had a better clinical outcome. Conclusion These data suggest that LINC01133 inhibits the EMT and metastasis by directly binding to SRSF6 as a target mimic, and may serve as a prognostic biomarker and/or an effective target for anti-metastasis therapies for CRC. Citation Format: Jianlu Kong, Honghe Zhang, Enping Xu, Qiong Huang, Jian Chen, Maode Lai. Long non-coding RNA LINC01133 inhibits epithelial-mesenchymal transition and metastasis in colorectal cancer by interacting with SRSF6. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 991.
P54 Vascular adhesion protein-1: a key player in the modulation of hepatic fibrosis
Authors: C Weston, E L Haughton, N M Westerlund, L C Claridge, J Pravin, D J Smith, D H Adams
Journal: Gut (2010)

Introduction  Vascular adhesion protein-1 (VAP-1) is a membrane-associated amine oxidase present on sinusoidal endothelium that supports lymphocyte recruitment to the liver. We have recently detected increased expression of VAP-1 in cirrhotic livers, and reported that a circulating soluble form is elevated in patients with fibrotic liver disease leading us to propose that VAP-1 plays a broader role in hepatic fibrosis.  Aim  To investigate the role of VAP-1 in the initiation, progression and resolution of hepatic fibrosis.  Method  Human: The distribution and expression of VAP-1 was investigated using multicolour confocal microscopy of normal and diseased human liver. Hepatic stellate cells (aHSC) and activated liver myofibroblasts (aLMF) were isolated from human liver tissue. Cell proliferation was studied using CyQuant. Apoptosis was investigated using a caspase-3 flow cytometry approach and cell detachment assay. Cell spreading was evaluated using xCELLigence impedence measurements. Modified Boyden chambers were used to assess cell migration. Mouse: Liver fibrosis was induced by CCl4 administration in wild-type C57BL/6 mice, wild-type mice dosed with anti-“VAP”-1 antibody and VAP-1 null mice. The degree of fibrosis and inflammatory infiltrate was assessed during active fibrosis and subsequent resolution using immunohistochemistry and qRT-PCR.  Results  VAP-1 was present on sinusoids and vascular endothelium in normal human liver but was markedly increased in expanded septa in fibrotic disease where it co-localised with markers of HSC and aLMF (CD90, -SMA) and extracellular matrix (ECM). Increased VAP-1 levels also correlated with the accumulation of advanced glycation end products in the scar, suggestive of a link between amine oxidase activity and modification of ECM. Cultured human aHSC and aLMF expressed VAP-1 mRNA and produced enzymatically active VAP-1 protein. Purified, soluble VAP-1 was a potent promigratory signal for lymphocytes and aHSC in vitro, possibly through amine oxidase activity. Soluble VAP-1 did not induce aHSC apoptosis or proliferation but was associated with an increase in cell spreading.  A role for VAP-1 in CCl4-induced liver fibrosis was confirmed in vivo. Both wild-type mice treated with a blocking anti-VAP-1 antibody and VAP-1null mice showed significantly reduced fibrosis after 8 weeks CCL4 compared with wild-type, and had accelerated resolution of fibrosis after cessation of CCl4. Wild-type mice receiving CCl4 also showed a significant increase in VAP-1 and elastin mRNA levels, mature macrophages, CD45-positive infiltrate and serum VAP-1 levels above that observed for VAP-1 null animals or those receiving antibody.  Conclusion  These data suggest a multifunctional role for VAP-1 in liver disease in which VAP-1 not only supports lymphocyte and HSC recruitment but also modulates ECM remodelling and fibrogenesis.
Abstract LB-005: TRIP13/PCH2 is a novel regulator of EGF-mTOR signaling promoting hepatocellular carcinoma development
Authors: Bettina Meissburger, Jessica Chan, Roldan de Guia, Stephan Herzig, Mauricio Berriel Diaz
Journal: Cancer Research (2016)

Abstract Hepatocellular carcinoma (HCC) is currently the third most common cause of cancer-related mortality with limited treatment options and bleak prognosis. The main risk factors for HCC have been linked to hepatitis infection, alcoholic liver injury, non-alcoholic fatty liver disease (NAFLD) and metabolic diseases. Current therapeutic options are limited, which could be due to the lack of understanding of the key cellular players and signalling pathways in HCC. In order to find novel regulators of HCC development, we surveyed expression data of human hepatocellular carcinoma (E-GEOD-25097) and found the AAA-ATPase Thyroid Hormone Receptor Interactor 13 (TRIP13) to be upregulated in tumorous tissue compared to non-tumorous tissue. Consistently, using a mouse model for HCC by injection of Diethylnitrosamine (DEN), we observed induced expression of TRIP13 in liver tumors compared to healthy liver tissue. Additionally, in a model of liver regeneration by partial hepatectomy, induction of TRIP13 coincided with a peak in cell proliferation in the regenerating liver. Strinkingly, Adeno-associated virus (AAV)-mediated hepatocyte-specific knockdown of TRIP13 impeded liver regeneration upon partial hepatectomy, suggesting an important role of TRIP13 in liver cell proliferation. Indeed, knockdown (KD) of TRIP13 severely impaired cell growth and proliferation in different human and murine HCC cell lines in vitro. To investigate the oncogenic potential of TRIP13 in vivo, we injected lentiviral infected cells subcutaneously into mice and measured tumor growth. Remarkably, knockdown of TRIP13 in Hepa1-6 cells led to the development of smaller tumors compared to control cells, whereas TRIP13-deficient Huh7 cells did not form any tumors. Interestingly, shRNA knockdown of TRIP13 in HCC cell lines showed decreased phosphorylation of key players in the mTOR signalling pathway and reduction of the downstream Cyclin D1 levels. Concurrently, the mRNA and protein expression of EGF receptor was also downregulated in TRIP13 KD-cells. Taken together, we identified a novel role of TRIP13 during hepatocyte proliferation both in liver regeneration and HCC. Additionally, our findings also support an oncogenic function of TRIP13 through the regulation of the EGFR-mTOR signalling axis. Citation Format: Bettina Meissburger, Jessica Chan, Roldan de Guia, Stephan Herzig, Mauricio Berriel Diaz. TRIP13/PCH2 is a novel regulator of EGF-mTOR signaling promoting hepatocellular carcinoma development. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-005.
BRPF1 is essential for development of fetal hematopoietic stem cells
Authors: Linya You, Lin Li, Jinfeng Zou, Kezhi Yan, Jad Belle, Anastasia Nijnik, Edwin Wang, Xiang-Jiao Yang
Journal: Journal of Clinical Investigation (2016)

Hematopoietic stem cells (HSCs) serve as a life-long reservoir for all blood cell types and are clinically useful for a variety of HSC transplantation-based therapies. Understanding the role of chromatin organization and regulation in HSC homeostasis may provide important insights into HSC development. Bromodomain- and PHD finger-containing protein 1 (BRPF1) is a multivalent chromatin regulator that possesses 4 nucleosome-binding domains and activates 3 lysine acetyltransferases (KAT6A, KAT6B, and KAT7), suggesting that this protein has the potential to stimulate crosstalk between different chromatin modifications. Here, we investigated the function of BRPF1 in hematopoiesis by selectively deleting its gene in murine blood cells. Brpf1-deficient pups experienced early lethality due to acute bone marrow failure and aplastic anemia. The mutant bone marrow and fetal liver exhibited severe deficiency in HSCs and hematopoietic progenitors, along with elevated reactive oxygen species, senescence, and apoptosis. BRPF1 deficiency also reduced the expression of multipotency genes, including Slamf1, Mecom, Hoxa9, Hlf, Gfi1, Egr, and Gata3. Furthermore, BRPF1 was required for acetylation of histone H3 at lysine 23, a highly abundant but not well-characterized epigenetic mark. These results identify an essential role of the multivalent chromatin regulator BRPF1 in definitive hematopoiesis and illuminate a potentially new avenue for studying epigenetic networks that govern HSC ontogeny.