tbuckley/cabot-search huggingface dataset:
Decreased expression of EZH2 is associated with ESR1 upregulation and response to anti-estrogens.
Authors: M Jansen, K Ruigrok-Ritstier, I van Staveren, J Helleman, E Reijm, M Look, M Meijer-van Gelder, A Sieuwerts, S Sleijfer, J Foekens, E Berns
Journal: Cancer Research (2009)

Abstract Abstract #6127 Background: In prostate and breast cancer high levels of Enhancer of Zeste Homolog 2 (EZH2) are associated with tumor progression. EZH2, a histone H3 methyl transferase, is part of the polycomb complex. Together with histone deacetylases (HDACs) EZH2 regulates “genome wide” gene transcription silencing. The aims of this study are a) to correlate EZH2 expression with endocrine therapy response in patients with recurrent disease treated with first-line tamoxifen monotherapy and b) to determine the role of EZH2 in endocrine therapy response using in vitro cell line models.&amp;#x2028; Material and Methods: EZH2 mRNA levels were measured with quantitative real-time PCR (qRT-PCR) in 297 retrospectively collected hormone receptor positive (HR+) primary breast tumor specimens of patients with recurrent disease who did respond (N=110) or were resistant (N=187) to first-line tamoxifen monotherapy. In vitro, EZH2 and estrogen receptor (ESR1) expression was downregulated with siRNAs in the human breast cancer cell line MCF7 and assessed for their sensitivity to the selective estrogen receptor degrader ICI164.384 after 96hrs treatment (N=3). To establish therapy response in vitro, cell number counts were determined. All p-values are two-sided and significant if P&amp;lt;0.05.&amp;#x2028; Results: In 297 HR+ breast tumors, EZH2 as continuous variable, associated significantly with poor response (OR= 0.67 [0.49-0.91]; P=0.001) and a shorter progression-free survival (PFS) (HR=1.28 [1.11-1.47], P&amp;lt;0.001). In the multivariate model with traditional predictive factors, the tertile with highest EZH2 levels was independently related with response (OR= 0.50 [0.26-0.98]; P=0.045) and PFS (HR=1.82 [1.33-2.49], P&amp;lt;0.001).&amp;#x2028; In vitro, EZH2 downregulation in MCF7 with siRNAs showed a significant decrease in cell number compared to the mock silenced cell line (40%). Moreover, ICI treatment of EZH2 silenced MCF7 cells resulted in a 70% cell number decrease versus 23% decrease in the controls (P&amp;lt;0.001). In addition, EZH2 downregulation is associated with a twofold upregulation with ESR1 (P&amp;lt;0.001). Conversely, silencing of ESR1 in MCF7 resulted did not alter EZH2 levels but, as expected, increases HER2 protein levels.&amp;#x2028; Conclusion: In primary breast tumors, high EZH2 mRNA levels are associated with poor outcomes after tamoxifen therapy. These results suggest that EZH2 may identify patients at risk for tamoxifen therapy failure. In vitro studies show that downregulation of EZH2 inhibits cell proliferation and on the other hand results in upregulation of ESR1 levels. The latter may explain the increased sensitivity to ICI164.384 of EZH2 silenced cells. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6127.
FRI0464 Work outcome in patients with ankylosing spondylitis over 12 years follow-up
Authors: J. D. Castillo-Ortiz, S. Ramiro, R. Landewé, D. van der Heijde, M. Dougados, F. van den Bosch, A. Boonen
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Although there is some literature on the impact of Ankylosing Spondylitis (AS) on the employment status or work disability (WD), the far majority of these studies are cross-sectional analyses and few compared work outcome with the general population. <h3>Objectives</h3> To understand the long-term impact of AS on participation in labour force over 12 years in a prospective cohort study, to identify predictors of an adverse work outcome (AWO) and to compare the incidence of WD over time with the general population. <h3>Methods</h3> Work related information and clinical characteristics were obtained from patients followed in the Outcome in AS International Study (OASIS). Patients who were at risk of having an AWO were included in the analysis, i.e. workers (either at baseline or resuming work later). AWO was defined as WD or a reduction in the number of working hours. Survival analysis was used to investigate AWO. With Cox regression, first baseline and secondly time-varying predictors were identified; the latter adjusted for 2 time dependent variables (change in social security system and market availability of anti-TNF). Incidence rate for WD among Dutch patients was compared with the general population using indirect standardization. <h3>Results</h3> Of 215 patients in the OASIS cohort, 139 (65%) were at risk for AWO (mean age 38.3 (SD 9.9) years, 75 % male, 81% HLA-B27, mean disease duration 9 (SD 6.8) years), of whom 11% (n=15) were not working at baseline but resumed work over time. A stepwise multivariable Cox analysis showed that higher baseline BASFI (HR 1.19; 95% CI 1.01-1.41) and Dutch origin (HR 3.85; 95% CI 1.37-10.84) predicted long-term AOW. In the time-lagged prediction analysis, only a higher BASFI (HR 1.27; 95%CI 1.08-1.50) significantly predicted AWO over time. Of 130 Dutch patients in working age, 9% (n=12) became WD over 12 years. The incidence of WD over 12 years was 2.9 (95% CI 1.2-4.6) and 1.22 (-0.42 - 2.87) times higher compared with the general population, for males and females, respectively. <h3>Conclusions</h3> Even in AS patients with already long disease duration, a substantial proportion remains at risk for an AWO. Self-reported physical function (BASFI) and system characteristics consistently influence AWO. <h3>Disclosure of Interest</h3> None Declared
Abstract 718: Optical molecular imaging of HER1-positive cancer using near-infrared PEGylated indocyanine green-labeled panitumumab.
Authors: Yang Zhou, Young-Seung Kim, Diane E. Milenic, Kwamena E. Baidoo, Martin W. Brechbiel
Journal: Cancer Research (2013)

Abstract Optical molecular imaging has attracted remarkable attention in recent years for cancer visualization and localization due to its characteristics of real-time, high sensitivity and specificity, cost-effectiveness and non-ionization. Indocyanine green (ICG) is the only clinically approved near-infrared fluorescent dye, and has been frequently employed to conjugate with antibodies or their fragments in the development of new cancer-targeted optical imaging agents. However, ICG molecules tend to form aggregates which cannot be removed by dialysis after antibody conjugation because of their high molecular weight. Previous data from our group has demonstrated that an amine-reactive PEGylated analogue of ICG (PEG-ICG) could successfully label an anti-HER1 antibody panitumumab with little aggregation compared with the non-PEGylated ICG. In this study, we present three higher equivalents (5×, 10×, and 20×) of PEG-ICG for panitumumab conjugation to yield ICG-PEG-panitumumab conjugates. Similar to previous studies, conjugation with PEG-ICG (5×) did not cause significant aggregates; whereas higher percentage of aggregates were observed for higher equivalents of PEG-ICG (∼10% and ∼20% for 10× and 20×, respectively). Collected PEG-ICG aggregates showed altered shape of absorbance spectra but not emission profile. In addition, the final molar ratios of ICG to panitumumab of the conjugates were 0.7, 2.3 and 6.0 for 5×, 10×, and 20×, respectively. Competitive radioimmunoassay demonstrated that the targeting moiety of the PEGylated bioconjugates was conserved. Fluorescence microscopy also demonstrated strong cellular binding and excellent fluorescent intensity of the bioconjugate (20×) in HER1-expressing A431 and SKOV3 cells. Comparatively, the conjugates with 5× and 10× PEG-ICG showed little or weaker fluorescent signal under the same exposure time. Hence, purified ICG-PEG-panitumumab bioconjugates are suitable candidates for the in vivo optical imaging of HER1-expressing tumors. Citation Format: Yang Zhou, Young-Seung Kim, Diane E. Milenic, Kwamena E. Baidoo, Martin W. Brechbiel. Optical molecular imaging of HER1-positive cancer using near-infrared PEGylated indocyanine green-labeled panitumumab. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 718. doi:10.1158/1538-7445.AM2013-718
DIAGNOSTIC VALUE OF A NON-INVASIVE COMPUTED TOMOGRAPHY ANGIOGRAPHY FOR ASSESSING HEMODYNAMIC SIGNIFICANCE OF NATIVE CORONARY ARTERY LESIONS USING FRACTIONAL FLOW RESERVE: A META-ANALYSIS
Authors: Hemang B. Panchal, Samit Bhatheja, Sreenivas P. Veeranki, Neil Barry, Timir Paul, Steven Lavine
Journal: Journal of the American College of Cardiology (2015)
HEART RATE REDUCTION AND EXERCISE PERFORMANCE IN RECENT ONSET HEART FAILURE WITH REDUCED EJECTION FRACTION: ARGUMENTS FOR BETA-BLOCKER HYPO-RESPONSE
Authors: Frederik Hendrik Verbrugge, Jeroen Vrijsen, Jan Vercammen, Lars Grieten, Matthias Dupont, Wilfried Mullens
Journal: Journal of the American College of Cardiology (2015)
Stat Bite: Underreporting of Melonama
Authors: J. Seiffert
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article Stat Bite: Underreporting of Melonama Get access Jennifer Seiffert Jennifer Seiffert Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 5, 4 March 1992, Pages 289–290, https://doi.org/10.1093/jnci/84.5.289 Published: 04 March 1992
Abstract 775: Mutant Wilms' tumor gene 1 devoid of zinc-fingers promotes proliferation of human hematopoietic progenitor cells <i>in vitro</i>.
Authors: Karina Vidovic
Journal: Cancer Research (2013)

Abstract The transcription factor Wilms’ tumour gene 1 (WT1) is present in some primitive hematopoietic cells and is highly expressed in the majority of lymphoid and myeloid leukemias, suggesting a role for WT1 in leukemogenesis. Mutations within the WT1 gene are present in 10-15 % of patients with cytogenetically normal acute myeloid leukemias and may be an independent predictor of poor clinical outcome. The mutations are most often heterozygous frameshift mutations leading to premature termination of the reading frame and therefore deletion of the entire DNA-binding zinc-finger domain. We have investigated the cellular effects of mutant WT1 protein lacking all four zinc-fingers, WT1(delZ). We report that expression of WT1(delZ) prolongs the proliferation of human hematopoietic CD34+ progenitor cells in vitro. Moreover, WT1(delZ) transduced cells express erythroid markers, including hemoglobin and elevated STAT5 protein levels, in part independently of addition of erythropoietin. STAT5 was increased by a posttranscriptional mechanism. The erythroid phenotype was also observed at global gene expression level, where WT1(delZ) caused coordinated up-regulation of genes associated with erythroid maturation, as well as genes related to cell division, while monocytic and neutrophil genes were down modulated. Our results indicate that WT1(delZ) promotes cell proliferation and erythroid differentiation at the expense of monocytes and granulocytes. Citation Format: Karina Vidovic. Mutant Wilms' tumor gene 1 devoid of zinc-fingers promotes proliferation of human hematopoietic progenitor cells in vitro. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 775. doi:10.1158/1538-7445.AM2013-775
Brown–Séquard Syndrome
Authors: A D Firlik, W C Welch
Journal: New England Journal of Medicine (1999)

Figure 1. A 21-year-old man presented with a stab wound of the left side of the neck (Panel A). Neurologic examination revealed right-sided Horner's syndrome, right hemiplegia, and complete loss of discriminatory, proprioceptive, and vibratory sensation below the level of C5 on the right side. On the left side, the patient had a loss of pain and temperature sensation below the level of C7, as well as a loss of proprioception in the leg. The findings were diagnostic of Brown–Sequard syndrome, with the additional finding of a loss of proprioception on the left. The patient was thought to have sustained . . .
Abstract 2650: A combined bioinformatics and GWAS approach identifies a functional 3′UTR insertion/deletion in <i>YES1</i> associated with bladder cancer risk
Authors: Hua Wei, Michelle AT Hildebrandt, Jian Gu, Yuanqing Ye, Maosheng Huang, Colin P. Dinney, Xifeng Wu
Journal: Cancer Research (2012)

Abstract Bladder cancer (BC) is diagnosed in over 70,000 individuals each year and its incidence is rising. There is a need for biomarkers to identify those at high risk, as well as for early detection. Large genome-wide association studies have identified multiple susceptibility loci; however, individually and combined, these variants only explain a small portion of the variation in BC risk. One possibility to explain the missing heritability is the effect of small insertions and deletions (INDELs). Because of the nature of these variations, they have a high likelihood for functional effects. Therefore, the purpose of study was to determine whether common INDELs are associated with BC risk. We retrieved 0.73 million INDELs and 7.72 million single nucleotide polymorphisms (SNPs) from the 1000 Genomes Pilot Project. Tagging-SNPs were identified for 0.48 million of these INDELs with r2 &amp;gt; 0.80 by PLINK. We then evaluated each tagging-SNP for association with BC risk in 969 BC cases and 957 controls. Using this approach, 5,110 INDELs were shown to be associated with BC risk (P &amp;lt; 0.05). We next focused on potentially functional INDELs located in exons, 3′ UTRs, 5′ UTRs or promoters. Approximately 50 INDELs fit this criterion, with a 2 basepair INDEL rs56342716 (-/AT) located in the 3′ UTR of YES1, a src kinase oncogene, being highly significant. The tagging-SNP for this INDEL, rs3786347, was associated with a 1.27-fold increase in BC risk (OR 1.27, 95% CI, 1.10-1.43, P = 6.08x10−4). These results were confirmed by direct genotyping of the INDEL in 822 BC cases and 802 healthy controls (OR 1.20, 95% CI, 1.04-1.38, P = 0.01). Reporter gene assay results revealed that the variant allele (AT) of rs56342716 disrupted the inhibitory effects of three microRNAs (miR-548e, miR-548f, and miR-548a-3p), providing a potential biological mechanism for the association with BC risk through increased YES1 levels. Together, these results provide evidence supporting a connection between a functional INDEL and BC risk while implicating YES1 in bladder cancer pathogenesis through a microRNA-mediated mechanism. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2650. doi:1538-7445.AM2012-2650
THE UNDERUTILIZATION OF SPIRONOLACTONE, AND RATES OF HYPERKALEMIA IN PATIENTS WITH CARDIOMYOPATHY HOSPITALIZED FOR HEART FAILURE
Authors: Mazin Majeed Hameed, Naila Choudhary, Farhad Nasar, saadia sherazi, Abrar Shah, KhalidAbdel Gadir
Journal: Journal of the American College of Cardiology (2012)
P-123 Prognostic factors for disease relapse in patients with neuroendocrine tumours who underwent curative surgery
Authors: A. Slagter, M. McNamara, D. Ryder, A. Lamarca, R. Hubner, W. Mansoor, D. OReilly, P. Fulford, H.-J. Klumpen, J. Valle
Journal: Annals of Oncology (2015)
P942 GOOD CLINICAL OUTCOMES FOLLOWING TRANSJUGULAR INTRAHEPATIC PORTOSYSTEMIC STENT-SHUNTS (TIPSS) IN BUDD CHIARI SYNDROME: LONG TERM FOLLOW UP IN A SINGLE CENTRE
Authors: D. Tripathi, R. Macnicholas, C. Kothari, L. Sunderraj, H. Al-Hilou, B. Rangarajan, F. Chen, K. Mangat, E. Elias, S. Olliff
Journal: Journal of Hepatology (2014)
APIXABAN COMPARED WITH WARFARIN IN PATIENTS WITH DIABETES AND NONVALVULAR ATRIAL FIBRILLATION IN THE ARISTOTLE TRIAL
Authors: Justin A. Ezekowitz, Basil Lewis, Renato Lopes, Daniel Wojdyla, John McMurray, Michael Hanna, Dan Atar, Maria Bahit, Matyas Keltai, Jose Lopez-Sendon, Prem Pais, Witold Ruzyllo, Lars Wallentin, John Alexander
Journal: Journal of the American College of Cardiology (2014)
The Sentinel Node in Breast Cancer — A Multicenter Validation Study
Authors: David Krag, Donald Weaver, Takamaru Ashikaga, Frederick Moffat, V. Suzanne Klimberg, Craig Shriver, Sheldon Feldman, Roberto Kusminsky, Michele Gadd, Joseph Kuhn, Seth Harlow, Peter Beitsch, Pat Whitworth, Roger Foster, Kambiz Dowlatshahi
Journal: New England Journal of Medicine (1998)

Pilot studies indicate that probe-guided resection of radioactive sentinel nodes (the first nodes that receive drainage from tumors) can identify regional metastases in patients with breast cancer. To confirm this finding, we conducted a multicenter study of the method as used by 11 surgeons in a variety of practice settings.
Reply
Authors: Elisabeth Krones, Wolfgang Erwa, Michael Trauner, Peter Fickert
Journal: Hepatology (2015)

Potential conflict of interest: Prof. Trauner consults for, advises, is on the speakers' bureau of, and received grants from Falk. He consults for and advises Albireo, Genfit, Intercept and Phenex. He is on the speakers' bureaus of Gilead, MSD, and Roche. He received grants from Intercept and Albireo. We greatly appreciate the interest and comments of Dr. Trivedi and colleagues related to our correspondence on serum alkaline phosphatase (ALP) levels as a useful marker for cholestasis in mouse models.1 Interestingly, strain differences in the multidrug resistance 2 (Mdr2) (Abcb4) gene knockout model have been previously observed in regard to degree of inflammation and tumor formation, with Friend virus B‐type/N (FVB/N) multidrug resistance 2 knockout (Mdr2−/−) mice being more affected than mice with a C75BL/6 background.2 In regard to the plateau of ALP levels in FVB/N Mdr2−/− mice, we believe that this might most likely reflect the stabilization of the cholestatic liver phenotype related to a "successful" wound‐healing process of bile ducts with stable fibrosis in this model, which may be even more likely achieved in the C57BL/6 background with less inflammation.3 Notably, bile duct injury and biliary fibrosis do not progress over time in this model and reach a plateau after 8 weeks.4 However, the underlying mechansims remain to be determined in detail. Primarily bone‐derived origin of ALP in 24‐week‐old FVBN Mdr2−/− mice seems to be rather unlikely, given that our previous studies showed normalization of ALP levels paralleling improvement of bile duct injury in norursodeoxycholic acid (norUDCA)‐treated Mdr2−/− mice5; the potential norUDCA effects on bone remain to be determined. We agree that future studies aiming at identification of novel disease‐modifier genes are warranted to shed more light on these interesting strain differences in this highly useful cholangiopathy model.
Abstract 4353: Identification of proteins regulated by mTOR in brain tumors of patients with tuberous sclerosis complex
Authors: Magdalena E. Tyburczy, Katarzyna Kotulska, Piotr Pokarowski, Jakub Mieczkowski, Wieslawa Grajkowska, Sergiusz Jozwiak, Bozena Kaminska
Journal: Cancer Research (2010)

Abstract Tuberous sclerosis complex (TSC) is characterized by the formation of benign tumors in many organs (mainly brain, heart, kidneys, skin or lungs) and is often associated with epilepsy, mental retardation and autism. Brain lesions include subependymal giant cell astrocytomas (SEGAs), low-grade tumors of a mixed glioneuronal lineage, which are the major cause of morbidity in children and young adults with TSC. The disease is caused by mutations in tumor suppressor genes: TSC1 (Hamartin) or TSC2 (Tuberin) leading to enhancement of mammalian Target Of Rapamycin (mTOR) kinase activity, deregulation of cell growth and tumorigenesis. Signaling via mTOR participates in complex genomic responses but its effectors in the brain are largely unknown. Therefore, we performed first genome-wide expression profiling on SEGAs using Affymetrix Human Genome arrays. We identified differentially expressed specific genes involved in tumorigenesis (up-regulated) and the nervous system development (down-regulated) in SEGAs and SEGA-derived cell cultures when compared to the normal brain or cultured human astrocytes. Out of genes differentially expressed in TSC, 11 were validated by real time PCR on independent tumor samples and 3 SEGA-derived cultures. Immunohistochemistry on paraffin-embedded sections confirmed up-regulated levels of several identified proteins in SEGAs. ANXA1, GPNMB, LTF, RND3, S100A11, SFRP4 and NPTX1 were shown to be mTOR effector genes in SEGA, as their expression was modulated by an mTOR inhibitor - rapamycin in SEGA-derived cell cultures. We are currently investigating the role of ANXA1, GPNMB and S100A11 in regulation of cell viability, migration, adhesion, size and shape of cultured SEGA cells using RNA interference. Furthermore, we observed that combined pharmacological inhibition of mTOR and extracellular signal regulated kinase (ERK) signaling pathways in SEGA cells affected their viability (MTT metabolism test), proliferation (BrdU assay), migration (scratch assay), morphology and size (volume, area and height measured with confocal microscopy). For the first time, we identified genes related to the occurrence of SEGA and regulated by mTOR, and showed an effective modulation of SEGA growth by inhibition of both mTOR and ERK signaling pathways, which could represent a novel therapeutic approach. The study was supported by Ministry of Science and Higher Education grant N N301 263536. 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 4353.
FUNCTIONAL EFFECTS OF SCN5A CHANNEL MUTATIONS AND THE RISK OF LIFE-THREATENING EVENTS IN TYPE 3 LONG QT SYNDROME
Authors: Yitschak Biton, Neils Otani, Ilan Goldenberg, Elsa Ronzier, Jayson Baman, Scott McNitt, Bronislava Polonsky, Jesaia Benhorin, Arthur A.M. Wilde, Peter Schwartz, Michael Ackerman, Shimuzu Wataru, Elizabeth Kaufman, Wojciech Zareba, Arthur Moss, Coeli Lopes
Journal: Journal of the American College of Cardiology (2016)
Cigarette Smoking and Risk of Myeloma
Authors: Ross C. Brownson
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article Cigarette Smoking and Risk of Myeloma Get access Ross C. Brownson Ross C. Brownson Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 14, 17 July 1991, Pages 1036–1037, https://doi.org/10.1093/jnci/83.14.1036 Published: 17 July 1991
Stat Bite: Trends in Melanoma Incidence in the U.S.
Authors: C. Kosary
Journal: JNCI Journal of the National Cancer Institute (1995)

Stat Bite: Trends in Melanoma Incidence in the U.S. Get access Carol Kosary Carol Kosary Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 20, 18 October 1995, Page 1511, https://doi.org/10.1093/jnci/87.20.1511 Published: 18 October 1995