tbuckley/cabot-search huggingface dataset:
PTH-089 Coeliac disease increases the risk of microvascular complications in patients with type 1 diabetes mellitus
Authors: J S Leeds, A D Hopper, M Hadjivassiliou, S Tesfaye, D S Sanders
Journal: Gut (2010)

<h3>Introduction</h3> There is an association between Coeliac disease (CD) and Type 1 diabetes however the effect of CD on important diabetes related outcomes is unknown. We previously identified 14 new cases of CD from a prospective study of patients with Type 1 diabetes (n=1000). We aimed to assess the effect of newly diagnosed CD on glycaemic control, lipid profile, renal function, retinopathy and peripheral neural function. <h3>Methods</h3> The CDDM patients (n=14) were age, sex, gender, weight and duration matched in a 2:1 ratio with patients having Type 1 diabetes alone (controls from the initial 1000 cohort). HbA1c, total cholesterol, HDL cholesterol, cholesterol:HDL ratio, triglycerides, eGFR and urinary albumin/creatinine ratio (aCR) were measured. Retinopathy was assessed through the annual eye screening programme. Peripheral nerve function was assessed by electrophysiological testing of 2 sensory and 2 motor nerves. Baseline values were recorded for both cases and controls and measurements repeated at 1 year in both groups. The CDDM group had been started on a gluten free diet. <h3>Results</h3> At baseline, there were no differences in age, duration, weight or average insulin dose (all p&gt;0.1). Those with CDDM had higher HbA1c (8.2% vs 7.5%, p=0.05), lower total cholesterol (4.1 vs 4.9, p=0.014) and lower HDL cholesterol (1.1 vs 1.6, p=0.017) compared to controls. More patients with CDDM had abnormal urinary aCR (45.5% vs 4.8%, p=0.009) and higher nephropathy stage (p=0.009) compared to controls. There was no difference in the prevalence of retinopathy overall but higher grades of retinal damage were more common in CDDM (58.3% vs 25%, p=0.02). The prevalence of peripheral neuropathy was 42.9% in CDDM and 15% in controls (p=0.11). At 1 year follow-up, HbA1c levels and lipid profile were not significantly different between cases and controls. There were no differences in renal profile between cases and controls however eGFR dropped in those with CDDM (95.5 to 84.0, p=0.003) reflecting two patients having renal deterioration (one started dialysis). There were no differences in the prevalence of retinopathy from baseline but one patient with CDDM underwent retinal laser therapy. There were also no changes in the prevalence of neuropathy. <h3>Conclusion</h3> CD has an adverse effect on glycaemic control, HDL cholesterol, renal function and retinal status but not peripheral neuropathy. Following a GFD, glycaemic control and lipid profile improved but renal and retinal changes were still significantly worse compared to controls. This is the first study to observe these microvascular effects. Further research is required to determine whether earlier detection and treatment of CD limits these effects.
MODELING GENETIC Diseases through Reprogramming of HUMAN Amniotic Liquid Derived CELLS
Authors: Noufissa Oudrhiri, Frank Yates, Olivier Feraud, Emilie Gobbo, Cecile BAS, Dominique Luton, Pierre Francois Ceccaldi, Gerard Tachdjian, Frank Griscelli, Ali G. Turhan, Annelise Bennaceur-Griscelli
Journal: Blood (2010)
Phase II trial of gemcitabine, carboplatin, and bevacizumab (Bev) in patients (pts) with advanced/metastatic urothelial carcinoma (UC).
Authors: A. V. Balar, M. I. Milowsky, A. B. Apolo, I. Ostrovnaya, A. Iasonos, A. Trout, A. M. Regazzi, I. R. Garcia-Grossman, D. J. Gallagher, D. F. Bajorin
Journal: Journal of Clinical Oncology (2011)

4566 Background: Effective treatment for pts with advanced UC unfit to receive cisplatin (C) is an unmet need. A phase III study showed limited benefit of gemcitabine (G) and carboplatin (Ca) with a median overall survival (OS) of 9.3 months (DeSantis ASCO 2010). The VEGF-axis is a viable pathway for UC treatment (Gallagher JCO 2010). We sought to test whether Bev, a monoclonal antibody against VEGF, could be safely added to GCa and improve outcomes. Methods: Primary endpoints (N=47) were 50% improvement over a median 4.8 months (mos) time to progression (TTP) seen with GCa alone (Linardou Urology 2004), and safety. Secondary endpoints were response rate (RR) and OS. TTP was defined using either date of progressive disease or date off-study due to adverse event (AE). Pts first received a dose of bevacizumab 10 mg/kg followed 2 weeks later by 6 cycles of G at 1,000 mg/m2on day(D) 1 and D 8, Ca at AUC 4.5 and Bev 15 mg/kg on D1 every 21 D. Pts with > stable disease (SD) continued Bev at 15 mg/kg q21 D for 18 additional doses. Response evaluations were done every 3 cycles of therapy. Results: 51 pts (37 M, 14 F; median age 67 [Range 42-83]) were enrolled from 6/06 to 6/10. Primary tumor sites were bladder (31), renal pelvis (18) and ureter (2). 35 pts (69%) had visceral disease including lung (22), liver (13), bone (9) and adrenal (2). 16 pts had LN only disease. Four pts did not receive > 1 cycle leaving 47/51 pts evaluable for RR and TTP, 51 for AE. RR by RECIST was 49% (23 pts; PR 20, CR 3). 11 had SD. Responses by MSKCC Risk Scores of 0, 1 and 2 were seen in 9/12(75%), 12/31 (39%), and 2/4 (50%) pts, respectively. 39% of pts had grade 3/4 toxicity; vascular thromboembolic events (VTE) occurred in 18%. The median TTP is 6.5 mos (95% CI 4.7, 7.8) and the median OS is 14.7 mos (95% CI 12.5, 25.8). Conclusions: Bev can be safely added to GCa. The 18% VTE rate is similar to the 17% rate seen with GCa alone (Apolo JCO 2009). Bev plus GCa had a TTP 1.7 mos greater than seen with GCa alone (Linardou Urology 2004) and an OS greater than previously observed for GCa in phase II and III trials (Bellmunt Eur J Cancer 2001; DeSantis ASCO 2010). The improvement in survival validates a similar survival observation seen with Bev and GC (Hahn, ASCO 2010) warranting further study.
Rational for a Combination of Bortezomib and Doxorubicin in the Treatment of Multiple Myeloma: A Pivotal Role for Mcl-1.
Authors: Steven Le Gouill, Klaus Podar, Jing Zhang, Teru Hideshima, Martine Amiot, Chauhan Dharminder, Jean-Luc Harousseau, Kenneth Anderson
Journal: Blood (2007)
Estrogen receptor β inhibits Wnt signaling
Authors: Anders M. Ström, Johan Hartman, Silke Kietz, Jan-Åke Gustafsson
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

2580 

Clinical studies are showing that women receiving hormone replacement therapy with estrogen have reduced colon cancer incidence. The main estrogen receptor in colon is the estrogen receptor β (ERβ). Expression of this receptor is often lost as colon cancer progress, which is an indication of that the effect of estrogen in colon is mediated by this receptor. We are proposing a mechanism whereby ERβ inhibits Wnt signaling. Increase of Wnt signaling is the most common cause of colon cancer. Using a TCF/β-catenin responsive reporter we show that in HEK293 cells this reporter was induced 250 times by co-transfection of a expression plasmid for non degraded β-catenin (S33Y). Co-transfection of a expression plasmid for ERβ and treatment with either 17β-estradiol or the specific ligand DPN reduced the β-catenin induction 240-fold. Furthermore, we show that the N-terminal portion of the receptor is crucial for repression of β-catenin induced activation of the TCF/β-catenin responsive reporter. Using the colon cancer cell line SW480 which have a high endogenous level of nuclear β-catenin we show that ERβ is inhibiting promoter activity of the well characterized Wnt targets c-myc and cyclin D1. We also used the colon cancer cell line HT29 to express ERβ under a tetracycline regulated promoter. By doing real time PCR on cDNA prepared from HT29 cells with and without ERβ expression we show that the mRNA levels of the Wnt targets c-myc and cyclin D1 is reduced by expression of the receptor. In addition, we observed that proliferation is strongly reduced when the receptor is expressed. These results suggest that it may be possible to use a specific ligand to ERβ as treatment or preventive treatment against colon cancer.
Abstract 19197: No Difference in Retention of BLS/AED Skills When Teaching Laypersons Using Four-stage and Two-stage Teaching Technique: A Randomized Comparison
Authors: Katrine Bjørnshave, Lise Q Krogh, Svend B Hansen, Mette A Nebsbjerg, Troels Thim, Bo Løfgren
Journal: Circulation (2015)

Introduction: The ability of laypersons to perform BLS/AED increases immediately after resuscitation training. Studies indicate that resuscitation skills rapidly decay after initial training, however it is unknown whether teaching technique influence retention of skill. Aim: To study the retention of BLS/AED skills three months after training when teaching laypersons using a four-stage and two-stage teaching technique. Methods: Laypersons (exclusion: health care professionals/students) were randomized to a standardized ERC BLS/AED courses using the four-stage teaching technique or to courses with the same content but modified to a two-stage teaching technique. Participants were tested in a simulated cardiac arrest scenario three months (±five days) after their course to assess retention of BLS/AED. Tests were video recorded and reviewed by two independent assessors blinded to training technique. Skills were assessed using the ERC BLS/AED assessment form. The primary endpoint was passing the test (17 out of 17 skills adequately performed). Results: A total of 160 participants were included in the study. No difference was found in pass rate immediately after training (diff. -1.6%; 95%CI -17.9%; 14.6%). There was no statistical difference in retention of BLS/AED skills (pass rate: both 11%, diff. -0.4%; 95%CI -28%-27%) three months after training . Total average skills adequately performed (of 17) were 13.7 versus 13.3 among laypersons trained with the four-stage (n=64) and the two-stage technique (n=64). No difference was found in number of chest compressions delivered per compression cycle (29±2.8 vs 30±3.1), chest compression rate (107±17 vs 108±19 minute-1), chest compression depth (46±11 vs 43±12 mm), number of effective rescue breaths between compression cycles (1.6±0.7 vs 1.6±0.5) and tidal volume (0.6±0.4 0.7±0.4 L). Conclusion: We found no difference in retention of BLS/AED skills among laypersons taught using a four-stage teaching technique compared to a two-stage teaching technique.
‘A picture is worth a thousand words’: image highlights from <i>Cardiovascular Research</i>
Authors: Diane Gal, Karin R. Sipido, Wouter Vandevelde
Journal: Cardiovascular Research (2016)

Communicating the main message or complex concepts/relationships in a publication with limited text is a challenge.As has been said before, this is when 'A picture is worth a thousand words' ('Speakers Give Sound Advice', Syracuse Post Standard, 28 March 1911, p. 18).An important part of the editorial process is to improve the readability, understanding, and attractiveness of publications for the end user/reader.As such, Cardiovascular Research in a joint effort of the editorial office, Oxford University Press and the European Society of Cardiology, decided to improve the use of images in the journal by both removing colour figure charges and providing free design support for priority publications by a graphics team of scientifically trained illustrators.The aim is (i) to enhance the quality of the message of the study, (ii) make the content more accessible to the broader readership of the journal, and (iii) to supply images for lectures and teaching to the whole community.For this latter aim, all these figures have now been made available to the Cardiovascular Research community in the Cardiovascular Research image repository online, which can be accessed at http://aca demic.oup.com/cardiovascres/pages/image_gallery/main_page.While an image gallery had been available before, the present introduction is of images that were for the largest part designed by the graphics team in an interactive process with the authors.Over the past 3 years since the introduction, the team has strived to optimize code and design for consistency in visualizing structures and pathways, e.g. by standardizing how commonly used items such as muscle cells are depicted in all images. Cardiovascular Research image repositoryHere, we introduce a brief overview of a first set of images in the repository that will be part of a novel web resource of information in Cardiovascular Research, to be launched in 2017.Reviews and original research articles with an accompanying editorial are highlighted.These studies that have been provided with design support were selected based on the timeliness and interest of the publication topic, bringing together both novelty and well-performed studies.In case of original research articles, the invited editorial positioned the research with an image to illustrate the novel concept.In 2014 and 2015, 78 figures received design support across 48 editorials and reviews, as well as two articles.
Hypothyroxinemia as a goal in cancer management by triiodothyronine (T3) substitution for supplemental L-thyroxine (T4) and T3 modulated hypothyroxinemia: Outcomes in a compassionate care population.
Authors: A. Hercbergs, O. Ashur -Fabian
Journal: Journal of Clinical Oncology (2011)

e19676 Background: Emerging data implicate thyroid hormone (T4) as pro-proliferative and angiogenic in solid cancers. Prolonged survival has been reported in association with spontaneous and intentional induced hypothyroidism. However hypothyroid symptoms are deterrents to patient compliance. Recently a thyroid hormone receptor was identified on integrin avbeta3 via which T4, at physiological concentrations, non-genomically activates mitogenesis and angiogenesis. In preclinical studies T3 is comparably active in glioma and lung cancer but mitogenic only in supraphysiological concentrations. Previous studies provide support for T3 modulated (via TSH inhibition) T4 depletion as a therapeutic intervention. T3 also prevents symptomatic hypothyroidism. Methods: Patients with stage IV solid tumors received T3 and methimazole. Initial TSH, FT4, T3 analysis was obtained and then monthly. All patients experienced hypothyroxinemia. Patients at dispersed sites with stage 4 solid tumors and limited survival received T3 and methimazole managed by a personal physician. Initial TSH, FT4, T3 analysis was obtained and then monthly. All patients experienced FT4 reductions to below reference range. Results: See table. Conclusions: Induced or maintained hypothyroxinemia in this small select group of poor prognosis patients was associated with generally favorableand some exceptional outcomes. Category 1. Hypothyroid on T4 supplementation at presentation—Switched to T3 (n=7: chemotherapy (CHEMO) and/or radiation (XRT) F. 62 Inflammatory Ca. breast C.R. 6 years + F 49 Ca. unknown primary - mets. C.R. 17 mo. + F. 80 NSC Lung - neuroendocrine - mets. C.R. 18 mo. + F. 56 Ca. Ovary s/p recurrence C.R. 24 mo. + F. 62 " stage 4 - skeletal mets. C.R. 24 mo. + M 65 Glioblastoma (GBM) C.R. 23 mo. + M 80 " 9 mo. Category 2. Euthyroid. Treated with T3 and methimazole (N=5) M 63 GBM 54 mo. M 45 " 11 mo. M 70 " 10 mo. + M 64 " 13 mo. + M 62 Small C.C. lung 18 mo. Category 3. On T3 supplementation at presentation F.67 Ca. pancreas - inoperable - 36 MO F 49 Ca. of breast - skeletal mets 9 + years Toxicity: hypothyroidism - T3 dosage adjusted.
27. Aberrant Expression of the Stem Cell microRNA-126 Induces B Cell Malignancy
Authors: Silvia Nucera, Francesco Boccalatte, Andrea Calabria, Tiziana Plati, Cristiana Fanciullo, Jose Manteiga, Fabrizio Benedicenti, Fabio Ciceri, Maurilio Ponzoni, Eugenio Montini, Luigi Naldini, Bernhard Gentner
Journal: Molecular Therapy (2015)

MicroRNAs are essential regulators of normal and malignant hematopoiesis. miRNAs are relevant for gene therapy, since they can be exploited to fine-tune the expression profile of vector constructs or to alter viral tropism (Gentner&Naldini, 2012). We exploited the hematopoietic stem cell (HSC) specific expression of miR-126 to de-target transgene expression from primitive compartment (Gentner et al, 2010; Chiriaco et al, 2014; Escobar et al, 2014) and described the function of miR-126 in HSC where it regulates the balance between quiescence and self-renewal (Lechman et al, 2012). We here report a novel role for miR-126 in the induction and maintenance of high-grade B cell malignancies. By ectopically expressing miR-126 in transplanted BM cells, we observed that up to 60% of mice (n=71) developed B cell malignancies. LV insertion site (IS) analysis revealed that all tumors were monoclonal. We then tracked back leukemic clone to different hematopoietic lineages prospectively purified from the mice 2-6 months before disease onset. IS sharing between normal lineages and leukemic clone suggests stem or multipotent progenitor cell as origin for most tumors. Importantly, we show that miR-126 is the direct cause of genesis and maintenance of leukemia, since leukemogenesis is abolished when miRNA expression is inhibited by doxycycline (doxy) using a tetracycline-repressible miR-126 cassette, and established symptomatic leukemia completely regresses when miR-126 is switched off by doxy through induction of apoptosis. Transcriptional profiling indicated that miR-126 regulates multiple genes in p53 pathway both in murine blasts and in normal human CD34+ cells. Previous work suggested expression of miR-126 in acute lymphoblastic leukemia (ALL) and germinal center lymphoma. To further establish the relevance of miR-126 in human disease, we measured miR-126 expression in blasts from 16 adult patients with ALL. miR-126 was highly expressed in most studied ALL cases (Phil+: n=11, Phil-: n=5), at similar levels as CD34+ cells. We then down-regulated miR-126 in primary blasts from human B-ALL patients (n=5), and we observed increased apoptosis and impaired engraftment in xenograft models after primary and secondary transplantation (miR-126/KD: n=32 mice; Ctrl: n=37 mice), demonstrating the relevance of miR-126 in human B-ALL. In conclusion, we present a novel spontaneous mouse model for high grade B cell malignancies which are addicted to miR-126 expression, provide insight into the dynamic process of leukemogenesis by clonal IS tracking and unveil key tumor signaling pathways controlled by miR-126. Down-regulation of miR-126 could be exploited as therapeutic strategy in ALL, since it would deplete leukemic cells while expanding normal HSC, two ways to restore normal hematopoieis.
Effectiveness of Peripheral Blood (PB) Molecular Monitoring by Quantitative RT-PCR (Q-PCR) in Phase II Acute Promyelocytic Leukemia (APL) Trial J0422.
Authors: Robert E Gallagher, Esther L Schachter- Tokarz, Lawrence E. Morris, Tianna Dauses, Ivana Gojo, Marcel P. Devetten, Katarzyna Jamieson, Robert L. Redner, Mikkael A. Sekeres, Ibitayo Owoeye, Steven D. Gore
Journal: Blood (2008)
Abstract 5580: Characterization of HPV integration sites in the human genome
Authors: Clara Bodelon, Micahel Untereiner, Svetlana Vinokurova, Mitchell J. Machiela, Nicolas Wentzensen
Journal: Cancer Research (2015)

Abstract Background. Persistent infection with carcinogenic human papillomaviruses (HPV) is known to be cause of the majority of anogenital cancers as well as some head and neck cancers. With the progression of the disease, the HPV genome is commonly integrated within the host DNA, although the mechanism by which integration may promote the progression of the disease is not well-understood. We performed a systematic review of integration events in HPV-related cancers and analyzed the genomic regions where these events occur. Methods. A PubMed search was performed to collect all published data on integration loci. A total of 29 articles were eligible for the analysis. Determination of genomic integration sites for papers that provided exact nucleotide sequences of integration sites or viral fusion regions was done by using the Basic Local Alignment Search Tool (BLAST, http://blast.ncbi.nlm.nih.gov/Blast.cgi) for the GRCh37/hg19 build. We used the Encyclopedia of DNA Elements (ENCODE) data to investigate if certain genetic features clustered with integrations sites. The Wilcoxon rank sum test was computed to compare the observed and expected distributions of minimal distances from the integration sites with known nucleotide positions to the different genetic features. Results. As of November 2014, approximately 1,200 integration events were reported in the literature from both tumors and cell lines. The majority of integrations sites (53%) were reported in cervical tumors, 9% in head and neck tumors, 4% of oropharyngeal tumors and 23% in cell lines,. Six percent and 2% of the integration sites were found in high-grade and low-grade cervical lesions, respectively. The majority of reported integration events (77%) were related to HPV16. We found that integration sites from tumors were closer to known genes (p &amp;lt;10−14) and CpG islands (p &amp;lt;10−9) than expected by chance. Among repetitive elements, long terminal repeats (LTR) were enriched in integration sites (P = 0.001). Open chromatin based on the FAIRE-seq peaks showed significant enrichment in integration sites (p &amp;lt;10−11). Conclusions. In summary, integration sites occur in genomic regions with enrichment for genetic elements, such as gene-rich regions, CpG sites, repetitive elements and open chromatin regions. This corroborates that accessible regions of the genome are preferentially targeted by integration and suggests that host genes may be functionally altered in development of HPV-related cancers. Citation Format: Clara Bodelon, Micahel Untereiner, Svetlana Vinokurova, Mitchell J. Machiela, Nicolas Wentzensen. Characterization of HPV integration sites in the human genome. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5580. doi:10.1158/1538-7445.AM2015-5580