tbuckley/cabot-search huggingface dataset:
Abstract 1236: Interferon consensus sequence binding protein (ICSBP)-induced cell proliferation mediated by TGF-β signaling pathway and MAPKs activation in HL-60 cells
Authors: Byung-Kiu Park, Hee Jung Kim, Jee Young Sung, Yong Nyun Kim
Journal: Cancer Research (2010)

Abstract Interferon consensus sequence binding protein (ICSBP), also known as IRF-8, is a member of the interferon (IFN)- regulatory factors (IRFs) induced by IFN-γ. ICSBP is mostly associated with differentiation of hematopoietic cells and known as a tumor suppressor. ICSBP contains the conserved transactivation domain which is shared by Smad4, suggesting a possible connection of IRF and TGF-β signaling. To test this connection, ICSBP was stably expressed in acute promyelocytic leukemia cell line, HL-60, that expresses little ICSBP. Although TGF-β receptor expression was undetectable in HL-60 cells, the expression of ICSBP in HL-60 (ICSBP-HL-60) resulted in an increased TGF-β receptor expression. Interestingly, even without TGF-β stimulation, both Smad and non-Smad pathways were activated in ICSBP-HL-60 cells compared with Mock-HL-60 cells, indicating ligand-independent activation of TGF-β receptor signaling. In addition, ICSBP expression augmented cell growth and suppression of ICSBP using siRNA specific for ICSBP abolished TGF-β receptor expression and attenuated cell growth. Consistently, reduction of TGF-βRI using siRNA or TGF-β receptor inhibitor, SB431542, also attenuated growth of ICSBP-HL-60 cells compared with Mock cells. Furthermore, MAPK pathways appeared to be involved in ICSBP-mediated cell growth because MAPKs are activated in ICSBP-HL-60 cells and specific inhibitor of this pathway was able to decrease the growth of ICSBP-HL-60 cells more sensitively than Mock-HL-60 cells. Suppression of ICSBP by siRNA effectively inhibited phosphorylation of MAPKs. All these data suggest that ICSBP up-regulates TGF-β receptor, activates ligand-independent TGF-β mediated signaling pathways, such as MAPKs activation, leading to cell proliferation. This study provides a new function of ICSBP in the regulation of cell proliferation 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 1236.
Bodies in Glass: Genetics, Eugenics, Embryo Ethics, by Deborah Lynn Steinberg
Authors: M. Warnock
Journal: BMJ (1997)

Deborah Lynn Steinberg / Manchester University Press, £35, pp 224 / ISBN 0 7190 4667 X

It may be of some interest to members of the medical profession hitherto unacquainted with postmodernist feminism to grapple with this book. Postmodernism is based on the premise that there is no such thing as truth corresponding with facts, there is only a variety of “discourses” representing different points of view. We tell each other stories, and these stories may direct us towards action, especially if they are told by powerful and persuasive people, but no story has ultimate authority. The feminist version of postmodernism emphasises the difference between stories told by women and those told by men, and Ms Steinberg is concerned with these discourses “around” (as she would …
Oleoyl‐Estrone
Authors: Xavier Remesar, José Antonio Fernández‐López, Marià Alemany
Journal: Medicinal Research Reviews (2011)

Abstract Oleoyl‐estrone (OE) is a powerful slimming agent that is also present in plasma and adipose tissue, where it is synthesized. It acts through the formation of a derivative W. OE effects (and W levels) are proportional to the dose. OE reduces food intake but maintains energy expenditure (thermogenesis). The energy gap is fulfilled with adipose tissue fat, sparing body protein and maintaining glycemia (and glycogen) with lower insulin and leptin levels. OE (in fact W) acts through specific receptors, different from those of estrogen. OE increases cholesterol catabolism, reducing hypercholesterolemia in obese rats. The main metabolic effect on adipose tissue is lowering of lipid synthesis, maintaining unchanged the intracellular lipolytic processes; the imbalance favors the progressive loss of fat, which is largely used by the muscle. OE administration induces additive effects with other antiobesity agents, such as β 3 ‐adrenergic agonists, forcing a massive loss of lipid. Corticosteroids markedly limit OE action by altering the liver control of lipogenesis. OE also inhibits the action of 17β‐hydroxysteroid dehydrogenase, decreasing the synthesis of β‐estradiol and testosterone. Discontinuous treatment allows for maximal efficacy both in rats and humans. OE has the advantage that the loss of fat is maintained and does not require additional dietary limitations.
Abstract LB-151: REV1 has critical roles in base excision repair intermediate-mediated transversion mutations but not for O6-methylguanine-initiated mutations in vertebrate cells.
Authors: Jun Nakamura, Xu Tian, James Swenberg
Journal: Cancer Research (2013)

Abstract Isogenic chicken DT40 cells deficient in various DNA repair pathways are a great tool for understanding the DNA damage response and mutagenesis caused by genotoxic agents by a comparison of mutants and parental DT40 cells. We recently found that ~55% of PIGO mutations are located at A:T sites with a high frequency of A to T transversion mutations in DT40 cells exposed to methyl methanesulfonate (MMS). These results suggest that A to T transversion mutations found in MMS exposure-derived PIGO mutant cells are due to base excision repair intermediates, such as abasic sites and single strand breaks originated from N3-methyladenine. It has been reported that DNA repair protein REV1 acts as not only as a deoxycytidine transferase across abasic sites but also as a scaffold protein to coordinate translesion DNA synthesis (TLS) polymerase switching. To address effects of REV1 on MMS-induced PIGO mutations in DT40 cells, we exposed REV1 knockout DT40 cells to low-dose MMS. REV1 knockout DT40 cells showed hyper-sensitivity in cell survival after MMS treatment with no increase in PIG-O mutations. These results indicate that PIG-O mutations in DT40 cells exposed to MMS are caused through REV1-dependent, but REV1 deoxycytidyl transferase-independent, TLS. In contrast to MMS, REV1 and parental DT40 cells showed similar toxicity and mutagenicity caused by a combination of low-dose N-methyl-N-nitrosourea and O6-benzylguanine. These results suggest that base excision repair intermediates appear to initiate REV1-dependent TLS, whereas, O6-methylguanine could be by-passed by replicative polymerases, such as polymerase delta complexes, with an associated increase in G to A transition mutations. Citation Format: Jun Nakamura, Xu Tian, James Swenberg. REV1 has critical roles in base excision repair intermediate-mediated transversion mutations but not for O6-methylguanine-initiated mutations in vertebrate cells. [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 LB-151. doi:10.1158/1538-7445.AM2013-LB-151
Ping-Pong Gaze
Authors: Muthiah Vaduganathan, Jacob H Johnson
Journal: New England Journal of Medicine (2015)

A 55-year-old man with alcoholic cirrhosis was found to be unresponsive at home. Examination revealed spontaneous, slow, horizontal, conjugate eye deviation, shown in a video, that alternated from one extreme to the other every 2 to 4 seconds.
S93 A Prospective Study Investigating Exacerbations, Healthcare Utilisation And Health Economic Indicators In Omalizumab Treated Severe Allergic Asthma Patients - Results From An Interim Analysis Of The Apex Ii Study
Authors: M. Masoli, A. Menzies-Gow, L. Dobson, J. Morjaria, R. Allcock, R. Niven
Journal: Thorax (2014)

<h3>Background</h3> A previous retrospective study of UK clinical practice demonstrated that omalizumab was associated with reduced exacerbations and healthcare utilisation in severe allergic asthmatics. <h3>Aim</h3> This multicentre observational study was conducted to confirm the observed retrospective findings prospectively in UK clinical practice. <h3>Methods</h3> Retrospective data were collected in the 12 months prior to and prospective data for up to 12 months following omalizumab initiation. The primary endpoint was the change in mean daily OCS dosage (reported previously). Secondary endpoints included changes in mean exacerbation frequency (defined as requiring hospital admission or Accident and Emergency (A&amp;E) attendance and/or a course of OCS (dosage increase of at least 10 mg/day for at least 3 days)), healthcare utilisation and missed days in education or at work. <h3>Results</h3> 235 patients were enrolled in the study at end December 2013 in 22 UK centres. Data for interim analysis were examined from patients with 12 months of assessment at database lock (n = 85, females, 54%, mean (±SD) age 44 yr (±13.2), mean (±SD) duration of asthma 26 yr (±14.0)). At the 16 weeks assessment 74/85 (87%) patients were classified as responders to omalizumab treatment. Comparing the 12 month periods prior to and following initiation of omalizumab, mean total exacerbations decreased by 51% from (mean, ±SD) 4.25 ± 2.73 to 2.07 ± 2.01 (mean difference 2.18, p &lt; 0.001), while mean exacerbations involving hospital visits decreased by 61% from 1.52 ± 2.00 to 0.59 ± 1.25 (difference 0.93, p &lt; 0.001). A&amp;E attendances were reduced from 54 to 19 (p &lt; 0.01) and inpatient hospitalisations from 85 to 36 (p &lt; 0.001). The percentage of average days absent from work or education due to sickness was more than halved in the 12 months pre and post omalizumab initiation reducing from 19.6% to 7.72% (n = 27, p &lt; 0.05). <h3>Conclusions</h3> The data prospectively confirms that omalizumab is associated with significant reduction in exacerbations, healthcare utilisation and societal burden in severe allergic asthma patients as was reported in the retrospective study.
GM-CSF receptor targeted treatment of primary AML in SCID mice using Diphtheria toxin fused to huGM-CSF
Authors: H Rozemuller, W Terpstra, EJC Rombouts, M Lawler, C Byrne, DJP FitzGerald, RJ Kreitman, JJ Wielenga, B Löwenberg, IP Touw, A Hagenbeek, ACM Martens
Journal: Leukemia (1998)
Abstract 2019: An epigenetic reactivation screen identifies pathways important in pleomorphic liposarcomas
Authors: Kara Pascarelli, Matthew Plantinga, Katherine Doyle, Chad Roberts, Yan Zhou, Margaret von Mehren, Dina Lev, Dominique Broccoli
Journal: Cancer Research (2011)

Abstract Treatment of soft tissue sarcomas with chemotherapy has met with limited success as few agents have demonstrated clinical efficacy, with standard therapies having a 25-30% response rate in large multi-institutional trials with current standard therapy of doxorubicin and ifosfamide. Pleomorphic liposarcomas have complex karyotypes, hindering identification of characteristic genome changes amenable to targeted treatment. Aberrant epigenetic silencing of genes is observed in cancers and is an established mechanism to abrogate tumor suppressor pathways. To gain insight into the biology of pleomorphic liposarcomas, we carried out an epigenetic reactivation screen to identify genes silenced by methylation of CpG dinucleotides. Three cell lines derived from pleomorphic liposarcomas were treated with 5-aza-2-deoxycytidine for 2 cell doublings prior to extraction of RNA. Total RNA from duplicate cultures of treated and untreated cells was hybridized to the Affymetrix U133plus2 expression chip. Initial filtering for only those genes affected in all three cell lines identified 201 genes with altered expression, 59 of which are down regulated and 142 of which are up regulated. We validated candidate genes by sequencing sodium bisulfite modified genomic DNA isolated from the three cell lines used in the reactivation screen. We chose candidates reported as being affected by promoter hypermethylation in other systems, stratifin (SFN); aka 14-3-3-σ, clusterin (CLU) and e-cadherin (CDH1). The data confirm that all candidates exhibit methylation of CpG islands located within 400 bp of the 5’ start site. To further validate candidates we tested the methylation status of SFN, CLU, and CDH1 in DNA isolated from12 pleomorphic liposarcomas, as well as DNA isolated from adipocytes, preadipocytes and adult adipose derived stem cells. Gene interaction networks were generated through the use of Ingenuity Pathway Analysis (Ingenuity® Systems, www.ingenuity.com). Conditional hypergeometric tests were done for testing the association of Gene Ontology using GOstats package in Bioconductor. Top scoring networks identified in this analysis included cancer, lipid metabolism, and cell cycle/death. In conclusion, the pathways identified here may form the basis for future development of targeted therapy against pleomorphic liposarcomas. 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 2019. doi:10.1158/1538-7445.AM2011-2019
PTU-204 Accuracy of visual estimation of adenoma size: a comparison with direct measurement in the pathology department
Authors: J Kinchen, E Harrod, K Wright, A Evans, N Chandra
Journal: Gut (2012)

<h3>Introduction</h3> Large adenomatous colonic polyps (&gt;10 mm) are associated with an increased risk of development of adenocarcinoma. Recent national guidelines require the ability to distinguish polyps above and below 10 mm in size to determine the optimal surveillance interval.<sup>1</sup> There is no standardised technique to measure polyp size either in the literature that underpins current guidelines or in practice. Visual estimation at endoscopy is widely used. Small prospective studies have shown this method to be inaccurate when compared to direct measurement in the pathology department.<sup>2</sup> This retrospective study aims to establish the accuracy of visual estimation of polyp size in usual clinical practice comparing to direct measurement. <h3>Methods</h3> A search for the word “polyp” was performed on the pathology reports for all colonoscopies and flexible sigmoidoscopies performed during a 1-year period. The pathology and endoscopy reports of the resultant cases were reviewed. Only adenomas completely removed by snare polypectomy without lifting and retrieved intact, where both endoscopic and measured sizes were recorded, and where the measured size was 5 to 15 mm were included. The direct measurement was subtracted from the visual estimate to give a size difference. The paired-sample t-test was used to test the null hypothesis that there was no difference between the mean sizes determined using the two methods for the group as a whole or for individual endoscopists. <h3>Results</h3> In a total of 4285 procedures, 79 polyps met the criteria for inclusion. In 39 cases (49%), the difference between visual estimate and direct measurement was &gt;2 mm. In ascertaining whether a polyp was above or below the 10 mm cut-off, visual estimate and direct measurement were discordant in 21 cases (27%). Despite these disparities, there was no overall tendency to over or underestimate polyp size for the group as a whole (mean difference 0.05 mm p=0.88). Of the 15 individual endoscopists, the two with the highest procedure counts both showed significant tendencies to underestimate polyp size, while a third showed significant overestimation. <h3>Conclusion</h3> In clinical practice, visual estimation of polyp size is often inaccurate. Individual endoscopists may systematically over or underestimate polyp sizes. Direct measurement should be preferred in determining surveillance intervals. <h3>Competing interests</h3> None declared. <h3>References</h3> 1. <b>National Institute for Health and Clinical Excellence</b>. <i>Colonoscopic Surveillance for Prevention of Colorectal Cancer</i>. 2011. http://www.nice.org.uk/guidance/CG118 2. <b>Schoen</b>, <i>et al.</i> The pathologic measurement of polyp size is preferable to the endoscopic estimate. <i>Gastrointest Endosc</i> 1997;<b>46</b>:492–6.
Improving NPI for breast cancer prognosis by including PR and HER-2 expression: own data and external validation set.
Authors: V Van Belle, O Brouckaert, S Van Huffel, E Schlichting, M Synnestvedt, B Naume, M Christiaens, P Neven
Journal: Cancer Research (2009)

Abstract Abstract #1080 The Nottingham Prognostic Index (NPI) classifies primary operable breast cancer patients into good (NPI ≤ 3.4) , intermediate (NPI 3.4-5.4) and poor (NPI ≥ 5.4) prognostic risk groups [Br J Cancer 1987; 56: 489–92]. Studies indicate a significant short term prognostic role for estrogen (ER), progesterone (PR) and HER-2 receptor on disease free survival (DFS). We proposed at SABCS 2007 to add PR and HER-2 expression to the NPI called improved NPI (iNPI) defined as (NPI) + (HER-2) – (PR), with HER-2 and PR '1' in case of amplified HER-2 and any PR-expression and '0' otherwise.&amp;#x2028; Internal validation of the iNPI was performed on 1928 breast cancer patients, primary operated between Jan 2000 and June 2005 at Univ Hospital Leuven. All patients were classified into any of the three NPI or iNPI risk group. Mean follow-up was 3.5 yrs and DFS was defined as previously stated [Breast Cancer Research and Treatment 2007; 106: S247-S247]. Out of the 601 patients classified as NPI low risk, 59 shifted towards the intermediate iNPI group. Comparison of DFS for the 59 shifted with the non-shifted patients from the low NPI class did not reveal a significant difference (p=0.129, log-rank test). 57 patients out of 935 and 136 out of 392 respectively classified as intermediate and high NPI group became high and intermediate risk according to the iNPI. In both cases, DFS of the shifted patients differed significantly from DFS of the non-shifted patients (p=&amp;lt;.001 en p=0.029). DFS of the shifted patients with the iNPI group they where shifted to was not/marginally significant (p=0.856, p=0.462 and p=0.047 for low, intermediate and high NPI respectively).&amp;#x2028; For external validation a dataset from the Breast Cancer Micrometastasis group in Oslo with 677 patients and known NPI, PR and HER-2 was used. Figure 1 confirms a significant difference between DFS of the shifted and the non-shifted patients within the highest NPI risk group (p=0.021). The difference in DFS between shifted and non-shifted patients was marginally non-significant (p=0.068) in the intermediate and non-significant in the low NPI group (p=0.116). The non-significant difference between DFS of the shifted groups with the DFS of the group they were shifted to was confirmed, with exception of the low NPI group (difference in systemic treatment) (p=0.040, p=0.621 and p=0.076 for low, intermediate and high NPI respectively).&amp;#x2028; We confirm the results from an internal study at the Univ Hospital in Leuven on an external dataset. Inclusion of the PR and HER-2 status into the NPI results in more homogenate risk groups concerning DFS.&amp;#x2028; &amp;#x2028; Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1080.
Paired-data analysis is required in the study by May et al.
Authors: A. Tamhane, G. McGwin
Journal: Endoscopy (2012)

We read with great interest the article by May et al. who evaluated the effectiveness of argon plasma coagulation (APC) for small-bowel bleeding. We would like to highlight some issues regarding the statistical analysis used in the study. The authors have used a t test to compare continuous variables (e. g. hemoglobin) and Fisher’s (exact) test for categorical variables (e. g. blood transfusion). For the before and after comparison of the APC group these tests are not appropriate because these are not independent observations. Therefore, a paired t test would be appropriate to compare hemoglobin (Table 3 of the manuscript); if the distribution of hemoglobin is skewed then a non-parametric test should be used. Similarly, in Table 4 of the manuscript comparing need for blood transfusion, a McNemar’s test should have been used. Furthermore, only one P value has been reported in the same row as the “Before APC” group whereas the comparison is between before and after APC groups; it is not clear whether this P value is for the Osler or the Non-Osler group or whether or not it included all of the patients. Considering the large differences reported in the study, we think that the results of significance tests would not change considerably. However, applying correct statistical analysis is crucial to any research study in order to avoid the danger of incorrect interpretation based on statistical tests.
Abstract 4036: Frequent downregulation of the transcription factor Foxa2 in lung cancer through epigenetic silencing
Authors: Daniela S. Basseres, Francesco D'Alò, Beow Y. Yeap, David A. Gonzalez, Hiroyuki Yasuda, Matthew Meyerson, Susumu Kobayashi, Daniel G. Tenen, Balazs Halmos, Daniel B. Costa
Journal: Cancer Research (2012)

Abstract PURPOSE: We sought to determine the mechanisms of downregulation of the airway transcription factor Foxa2 in lung cancer and the expression status of Foxa2 in non-small-cell lung cancer (NSCLC). METHODS: A series of 25 lung cancer cell lines were evaluated for Foxa2 protein expression, FOXA2 mRNA levels, FOXA2 mutations, FOXA2 copy number changes and for evidence of FOXA2 promoter hypermethylation. In addition, 32 NSCLCs were sequenced for FOXA2 mutations and 173 primary NSCLC tumors evaluated for Foxa2 expression using an immunohistochemical assay. RESULTS: Out of the 25 cell lines, 13 (52%) had undetectable FOXA2 mRNA. The expression of FOXA2 mRNA and Foxa2 protein were congruent in 19/22 cells (p=0.001). FOXA2 mutations were not identified in primary NSCLCs and were infrequent in cell lines. Focal or broad chromosomal deletions involving FOXA2 were not present. The promoter region of FOXA2 had evidence of hypermethylation, with an inverse correlation between FOXA2 mRNA expression and presence of CpG dinucleotide methylation (p&amp;lt;0.0001). In primary NSCLC tumor specimens, there was a high frequency of either absence (42/173, 24.2%) or no/low expression (96/173, 55.4%) of Foxa2. In 130 patients with stage I NSCLC there was a trend towards decreased survival in tumors with no/low expression of Foxa2 (HR of 1.6, 95%CI 0.9-3.1; p=0.122).CONCLUSIONS: Loss of expression of Foxa2 is frequent in lung cancer cell lines and NSCLCs. The main mechanism of downregulation of Foxa2 is epigenetic silencing through promoter hypermethylation. Further elucidation of the involvement of Foxa2 and other airway transcription factors in the pathogenesis of lung cancer may identify novel therapeutic targets. 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 4036. doi:1538-7445.AM2012-4036