tbuckley/cabot-search huggingface dataset:
Abstract 2484: Whole-exome sequencing of a rare case of familial childhood acute lymphoblastic leukemia
Authors: Jasmine Healy, Virginie Saillour, Jean-François Spinella, Ramon Vidal, Eric Bareke, Chantal Richer, Mathieu Larivière, Stephan Busche, Bing Ge, Alexandre Montpetit, Tomi Pastinen, Daniel Sinnett
Journal: Cancer Research (2012)

Abstract Acute lymphoblastic leukemia (ALL) is the most common cancer in children, accounting for approximately 25% of all pediatric cancer cases. However, familial childhood ALL is extremely rare. Few families with multiple non-twinned siblings diagnosed with childhood ALL have been reported, and to date no highly penetrant leukemia susceptibility gene(s) has been identified to explain this uncommon occurrence. We postulated that pure (nonsyndromic) familial childhood ALL could result from the accumulation of disadvantaging rare DNA variants in predisposing genes or biological pathways. To address this hypothesis, we used next-generation sequencing technologies to capture and re-sequence the whole-exomes of a family comprising the mother, father and two male non-twinned affected siblings (sibling A and sibling B). Both brothers were diagnosed with the identical ALL subtype, pre-B hyperdiploid childhood ALL, three years apart. The similar clinical and molecular characteristics of the siblings suggest shared etiologic factors. Using the Agilent SureSelect All Human Exon 38 Mb Kit and the SOLiD 3 Plus system, we captured and sequenced a total of 17.5 Gb of sequence for the entire family, with a mean coverage of 47X. For each individual, approximately 96% or 36.4 Mb of the targeted bases were covered α1X and 70% of the targeted bases or 26.4 Mb passed our thresholds for variant calling. We identified 52,038 positions at which the called allele(s) differed from the reference genome in at least one of the four family members. In total, we identified 19,096 germline variants in sibling A and 28,061 in sibling B, of which 2,355 (12.3%) and 2,125 (7.6%), respectively, were previously undiscovered in dbSNP. We investigated non-synonymous homozygous variant and compound heterozygous positions shared between the siblings, as well as genes/pathways with increased burden of rare non-synonymous variants. Based on several criteria (PolyPhen annotation, known allele frequency, etc.), we identified variants that are strong functional candidates to explain this case of pure familial childhood ALL. In parallel, high-density genotyping was also performed (Illumina Omni 2.5M) for quality control and structural variant detection, allowing the identification of putatively shared copy number variants that may also be involved in leukemogenesis. Though independent validation and functional assessment is required, this is the first study to identify genetic factors involved in pure familial childhood ALL. 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 2484. doi:1538-7445.AM2012-2484
Hypermetabolic Mesenteric Brown Adipose Tissue on Dual-Time Point FDG PET/CT in a Patient With Benign Retroperitoneal Pheochromocytoma
Authors: Aisheng Dong, Yang Wang, Jianping Lu, Changjing Zuo
Journal: Clinical Nuclear Medicine (2013)

Intense FDG uptake of the mesenteric brown adipose tissue (BAT) is rare. We present a case of benign retroperitoneal pheochromocytoma showing multiple hypermetabolic regions corresponding with common locations of BAT. Furthermore, the mesenteric region showed intense FDG uptake, with SUVmax of 10.6. FDG PET/CT findings of this case supports the previous theories that the incidence of BAT may be higher in patients with pheochromocytoma than in patients without, and the intra-abdominal fat of human adults, including the omental fat, which is brown adipose tissue in infancy, becomes reactivated in the presence of high circulating noradrenaline concentrations.
INITIAL RESULTS FROM THE CASCADE-FH REGISTRY: CASCADE SCREENING FOR AWARENESS AND DETECTION OF FAMILIAL HYPERCHOLESTEROLEMIA
Authors: Emily Claire O’Brien, Emil DeGoma, Patrick Moriarty, MacRae F. Linton, Michael Shapiro, Bart Duell, Christie Ballantyne, William Neal, Zahid Ahmad, Danielle Duffy, Lisa Hudgins, Linda Hemphill, James Underberg, Karol Watson, Samuel Gidding, Seth Baum, Kristen Dilzell, Joyce Ross, David Pickhardt, Iris Kindt, Daniel Rader, Katherine Wilemon, Matthew Roe, Joshua Knowles
Journal: Journal of the American College of Cardiology (2015)
Erratum: Corrigendum: Mutations in the transcriptional repressor REST predispose to Wilms tumor
Authors: Shazia S Mahamdallie, Sandra Hanks, Kristen L Karlin, Anna Zachariou, Elizabeth R Perdeaux, Elise Ruark, Chad A Shaw, Alexander Renwick, Emma Ramsay, Shawn Yost, Anna Elliott, Jillian Birch, Michael Capra, Juliet Gray, Juliet Hale, Judith Kingston, Gill Levitt, Thomas McLean, Eamonn Sheridan, Anthony Renwick, Sheila Seal, Charles Stiller, Neil Sebire, Thomas F Westbrook, Nazneen Rahman
Journal: Nature Genetics (2016)
Cui bono? Selfish goals need to pay their way
Authors: David Spurrett
Journal: Behavioral and Brain Sciences (2014)

Abstract The target article falls short of explaining the phenomena, including motivational conflict, that it sets out to. The two main reasons for this are: (1) It is unclear in what sense goals are “selfish”; (2) We need an account of how selfish goals motivate people. If selfish goals are not in the replication business, then what is in it for them? And if they do not offer people something that they want, how do they ever influence what people do?
FRI0361 The Effects of Adiponectin on the Expression of Endocan in Fibroblast-Like Synoviocytes
Authors: S.-J. Hong, Y.-A. Lee, S.-H. Lee, R. Song, H.-I. Yang, K.S. Kim, J.-W. Hur, S.-S. Kim
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Endocan, previously called endothelial cell-specific molecule (ESM-1), has been studied as a pro-angiogenic factor in tumor tissues. Endocan binds CD11a/CD18 integrin (also called LFA-1 for Leukocyte Function-associated Antigen-1) on human leukocytes, consequently inhibiting its binding to ICAM-1 and preventing transendothelial migration. These physiological functions of endocan may also be involved in the angiogenesis of pannus in rheumatoid arthritic joints, which shows tumor-like growth. Here, we describe for the first time that endocan expression is increased in arthritic synovial tissues and that adiponectin is one of the important factors that increases endocan expression in synovial cells. <h3>Objectives</h3> This study was performed to evaluate whether endocan expression, which is known to be involved in tumor angiogenesis, is increased in rheumatoid arthritic tissues. In addition, we examined the contribution of adiponectin in the regulation of endocan expression in arthritic joints. <h3>Methods</h3> Arthritic synovial tissues from patients with rheumatoid arthritis (RA) and osteoarthritis (OA) were immunostained with antibodies to endocan and VEGF. Synovial cells and human umbilical vein endothelial cells (HUVEC) were cultured and stimulated with IL-1β and/or adiponectin. The mRNA and protein levels of endocan were measured by PCR and ELISA, respectively. <h3>Results</h3> Endocan expression was greatly increased in inflammatory sites of RA synovial tissues. In OA tissues, its expression was higher in tissues with moderate to severe inflammation than in those with mild inflammation. <i>In vitro</i> expression levels of endocan and VEGF in endothelial and synovial cells were differentially increased in response to IL-1β stimulation. Adiponectin was a more potent stimulator of endocan than was IL-1β at their respective physiological concentrations in synovial cells. Endocan silencing by siRNA transfection in synovial cells decreased <i>in vitro</i> cell migration and invasion. <h3>Conclusions</h3> Adiponectin is an important factor in the stimulation of endocan expression in synovial cells. Adiponectin-induced endocan expression in synovial cells may stimulate cell migration and invasion as well as angiogenesis in the pannus of arthritic joints. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3705
Iodide-Induced Thyrotoxicosis in Boston
Authors: Apostolos G. Vagenakis, Chiu-an Wang, Albert Burger, Farahe Maloof, Lewis E. Braverman, Sidney H. Ingbar
Journal: New England Journal of Medicine (1972)

Abstract The syndrome of iodide-induced hyperthyroidism (Jodbasedow) is not common and has been reported to occur in patients with iodine-deficient goiter after iodide replenishment. As part of a larger study to assess the effects of iodide administration on thyroid hormone synthesis in normal subjects and in patients with various underlying disorders of the thyroid, iodides (5 drops of a saturated solution of potassium iodide) were administered to eight patients with nontoxic goiter residing in Boston, an area of iodine sufficiency. Hyperthyroidism developed during and after iodide administration in four of the eight — an unexpectedly high frequency. This finding suggests that the homeostatic mechanism controlling thyroid hormone synthesis and release in these patients is not functioning normally. We recommend that large doses of iodides not be administered to patients with nontoxic goiter.
The role of endoscopic ultrasonography in diagnosis and management of the subepithelial lesions in the upper gastrointestinal tract
Authors: M Jinga, C Gheorghe, T Nicolaie, LS Gheorghe, F Vasilescu, P Nuta, R Costache, DG Popescu, LF Florea, R Brescan, E Michiu, T Tabaran
Journal: Endoscopy (2006)

Background: Endoscopic ultrasound (EUS) is the most appropriate technique for diagnosing of submucosal tumors (SMTs) or extraluminal compressions (EC) in the gastrointestinal (GI) tract. Frequent use of GI endoscopy has increased the detection of these tumors. Endoscopic biopsy is limited to the superficial mucosa and is not useful in diagnosis. EUS can clearly define the intramural or extrinsic nature, the layer of origin in the GI wall and the ultrasound characteristics.
PREDICTORS OF OUTCOMES BY CARDIAC MAGNETIC RESONANCE IN PATIENTS WITH PULMONARY HYPERTENSION
Authors: Carlos Andres Gonzalez-Lengua, Chirag Agarwal, Pirkash Kumar, Maria Eduarda Siqueira, Jose Manuel Garcia-Ruiz, Ziad Sergie, Jagat Narula, Valentin Fuster, Javier Sanz
Journal: Journal of the American College of Cardiology (2016)
P1155 SAFETY AND EFFICACY OF PEG-IFNa2a AND RIBAVIRIN FOR TREATMENT OF HEPATITIS C IN SARDINIAN ADULT PATIENTS WITH THALASSEMIA MAJOR: A SINGLE CENTRE REAL LIFE EXPERIENCE
Authors: S. Casu, C. Balestrieri, F. Figorilli, S. Onali, G. Serra, L. Chessa, M.E. Lai
Journal: Journal of Hepatology (2014)
Combined use of endoscopic ultrasound and confocal endomicroscopy for complete EMR of early gastric neoplasia
Authors: Ji Rui, Zuo Xiu-Li, Li Chang-Qing, Li Zhen, Li Yan-Qing
Journal: Endoscopy (2011)

Endoscopic mucosal resection (EMR) is an alternative to surgery for removal of superficial gastric neoplastic lesions.
New Screening Tool Maps Genetic Patterns of Solid Cancers
Authors: J. Ziegler
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article New Screening Tool Maps Genetic Patterns of Solid Cancers Get access Jan Ziegler Jan Ziegler Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 24, 20 December 1995, Pages 1830–1832, https://doi.org/10.1093/jnci/87.24.1830 Published: 20 December 1995
Sequential strategy with ALK-TKIs for ALK-positive advanced NSCLC: results of a multicenter analysis
Authors: M.F. Currà, D. Iacono, A. Delmonte, G. Metro, L. Paglialunga, A. Dubini, C. Bennati, R. Giusti, L. Crino, I. Sperduti, R. Chiari
Journal: Annals of Oncology (2015)
Mental Retardation in Children of Phenylketonuric Mothers
Authors: C. Charlton Mabry, Joseph C. Denniston, James G. Coldweu
Journal: New England Journal of Medicine (1966)

PREVIOUSLY, we reported 3 phenylketonuric mothers who had 1, 5 and 8 nonphenylketonuric children, all mentally retarded.1 We postulated that the metabolic derangement of the mothers caused the mental defect in the children. Two mothers were greatly retarded, and the third was moderately so. Two of the fathers, though unavailable for study, had normal children through other marriages. Because 2 of these mothers were institutionalized and few phenylketonuric mothers have been detected, we were unable to assess fully the significance of our findings.Since our original report we have detected 3 additional phenylketonuric mothers who are functioning adequately in society; . . .
AB0150 Tocilizumab Does not Induce Apoptosis in Neutrophils in Vitro
Authors: T. Witte, S. Ulrich, S. Buyny, R.E. Schmidt, R. Jacobs
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Tocilizumab is an inhibitor of the IL-6 receptor and is highly efficient in the treatment of rheumatoid arthritis. Leucopenia has been observed in 10% of the patients, which has been partly attributed to concomitant methotrexate therapy, but may also occur in monotherapy with tocilizumab. The pathomechanism of the leucopenia remains unclear. <h3>Objectives</h3> To study the influence of tocilizumab on the function and on apoptosis of neutrophils. <h3>Methods</h3> Granulocytes from the peripheral blood of 13 healthy controls were incubated overnight with medium only or with medium containing various concentrations between 0.8 and 800 μg/ml of tocilizumab. The concentrations were chosen based on the recommended dose of tocilizumab of 8 mg/kg. The apoptosis rate of the granulocytes was studied by Annexin-V/7-AAD staining using flow cytometry. In addition, the surface expression of the cell adhesion receptor CD11b, the chemokine receptors CD181 and CD182 and of CD62L, indicating an enhanced migration capacity, were measured. The adhesion of granulocytes to a layer of human vascular endothelial cells (HUVEC) after 1 hour of incubation was studied by harvesting and counting non-bound cells. <h3>Results</h3> Tocilizumab was found to bind to neutrophils. The treatment of neutrophils with tocilizumab slightly reduced the expression of CD62L at the highest dose studied and almost doubled the adhesion to HUVEC in vitro in the whole dose range. The rate of apoptosis and of cell survival was not affected. <h3>Conclusions</h3> Neutropenia during treatment with tocilizumab appears to be a consequence of enhanced cell adhesion to endothelia and presumably migration rather than of apoptosis and cell death. <h3>Acknowledgements</h3> Chugai Pharma Marketing Ltd for financial support of the study. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2660
PTU-056 The effect of hepatitis C infection on the utility of alpha-fetoprotein as a surveillance marker for tumour recurrence following liver transplantation for hepatocellular carcinoma
Authors: J R L Maggs, J G O'Grady, M A Heneghan, K Agarwal, V Aluvihare, P Srinavasan, A Prachalias, N Heaton, A R Suddle
Journal: Gut (2012)

<h3>Introduction</h3> In selected patients, liver transplantation (LT) is considered a curative treatment for hepatocellular carcinoma (HCC). With the application of strict eligibility criteria the risk of tumour recurrence can be minimised but never entirely eliminated. Historically, HCC recurrence is associated with a poor prognosis; however the new and evolving systemic therapies may improve outcomes. Hence, there may be a potential beneficial role for early diagnosis. Although, serum alpha-fetoprotein (AFP) measurement is commonly employed in HCC surveillance in at-risk patients, its role following LT for HCC is not clearly defined. Therefore, we have explored (1) the utility of AFP as a biomarker for tumour recurrence following LT in patients with HCC and (2) the influence of liver disease aetiology on its diagnostic performance. <h3>Methods</h3> The clinical characteristics, laboratory parameters and outcomes of 302 patients with HCC who underwent LT between January 1999 and July 2011 at our institution were reviewed. Serum AFP levels following LT were analysed and the area under a receiver-operator characteristic curve (AUC) calculated to assess the performance of AFP as a diagnostic test for HCC recurrence. <h3>Results</h3> Recurrent HCC was observed in 13% of patients during the follow-up period. Recurrence was associated with higher pre-LT AFP (98 ng/ml vs 11.5 ng/ml, p&gt;0.001), vascular invasion in the liver explant, and greater tumour size. Following LT, the median time from initial rise in serum AFP to the diagnosis of recurrence was 16 weeks. In our cohort, AFP was an effective predictor of HCC recurrence (AUC 0.843) and using a cut-off value of ≥10 ng/ml was an excellent exclusion test (negative predictive value 0.94). Furthermore, its performance was superior in patients with AFP-secreting tumours at LT, in comparison to those with non-secreting tumours (AUC 0.892 vs 0.710). Patients with chronic hepatitis C (CHC), in comparison to non-infected patients, were younger (56 years vs 60 years, p=0.887) and had a lower MELD score (13 vs 10 ng/ml, p=0.002) but higher serum AFP (21 ng/ml vs 10 ng/ml) at LT. However, there was no difference in recurrence rates between groups. In patients with CHC, AFP was an inferior predictor of HCC recurrence, in comparison non-CHC patients (AUC 0.769 vs 0.887). <h3>Conclusion</h3> We, therefore, conclude that serum AFP measurement is a potentially useful surveillance investigation for tumour recurrence post-LT for HCC particularly in patients without CHC. <h3>Competing interests</h3> None declared.
Safety profile of nivolumab (NIVO) in patients (pts) with advanced melanoma (MEL): A pooled analysis.
Authors: Jeffrey S. Weber, Scott Joseph Antonia, Suzanne Louise Topalian, Dirk Schadendorf, James M. G. Larkin, Mario Sznol, Helen Y Liu, Ian Waxman, Caroline Robert
Journal: Journal of Clinical Oncology (2015)

9018 Background: NIVO is a programmed death-1 (PD-1) immune checkpoint inhibitor which has shown durable tumor responses in multiple cancer types and prolongs overall survival in pts with MEL. The objective of the current analysis is to describe the safety profile of NIVO across recent MEL studies, including 4 studies in which guidelines for the management of adverse events (AEs) were utilized. Methods: A retrospective safety review was conducted for 4 ongoing phase I–III trials, in which MEL pts received NIVO 3 mg/kg Q2W until disease progression or unacceptable toxicity. Data were included from pts who received at least 1 dose of NIVO, and included assessments of AEs, select AEs (immune-related etiology), time to onset and resolution, and the use as well as impact of immune modulating agents (IMs). Results: A total of 576 patients received NIVO for a median of 3.7 months; 312 (54%) had received prior ipilimumab (IPI). The most frequent drug-related AEs of any grade were fatigue (25%), pruritus (17%), diarrhea (13%), and rash (13%); grade 3–4 drug-related AEs occurred in 10% of all pts, and in 8% of pts with prior IPI. No drug-related deaths were reported. Drug-related select AEs of any grade were most frequent in the skin (34%), GI tract (13%), endocrine glands (8%) and liver (4%); grade 3–4 select AEs occurred in 4% of pts. Median time to onset of drug-related select AEs ranged from 5 wks for skin AEs to 15 wks for renal AEs. IMs were administered to 166/474 pts (35%) in phase III studies to manage AEs; 114 pts (24%) received systemic corticosteroids. Among 21 pts with grade 3–4 drug-related select AEs, all but 1 pt with a skin AE resolved with IMs. Median time to resolution ranged from 3 wks for hepatic AEs to 29 wks for skin AEs. The objective response rate was 44% in pts who received an IM and 36% in those who did not; time to response was similar (median 9 wks), and the median duration of response was not reached for either pt subgroup. Conclusions: In this pooled analysis, drug-related AEs with NIVO monotherapy were primarily low grade and the incidence of grade 3–4 drug-related AEs was not affected by prior IPI. Nearly all drug-related grade 3–4 select AEs resolved with use of IMs, which did not appear to impact on tumor response.
OP0271 Differential regulatory functions of HIF-1α and HIF-2α during angiogenesis of human microvascular endothelial cells (HMECS)
Authors: M. Hahne, S. Luetkecosmann, C.L. Tran, C. Strehl, M. Fangradt, M. Jakstadt, G. Duda, P. Hoff, T. Gaber, G.-R. Burmester, F. Buttgereit
Journal: Annals of the Rheumatic Diseases (2013)

Background Hypoxia and angiogenesis are features of inflamed and injured tissues. The transcription factors Hypoxia inducible factor (HIF)-1α and (HIF)-2α control cellular metabolic response to decreased oxygen tension thereby promoting angiogenesis and having implications on the pathogenesis of RA. Objectives We focused on the effects of HIF-1α and HIF-2α on angiogenesis and developed a human microvascular endothelial cells (HMEC) lentiviral based knockdown system for both transcription factors allowing us to analyze angiogenesis of HMECs under hypoxia in the absence of HIF-1α or HIF-2α, respectively. Methods Specific knockdown of HIF-1α or HIF-2α was achieved using lentiviral-based shRNA technology. The reduction of HIF-1α or HIF-2α was confirmed on transcriptional and translational level by realtime RT-PCR and Western blot. Angiogenesis of transduced HMECs in comparison to scrambled cells was studied by investigating both tubuli and node formation under hypoxia (<1% O2). Expression of hypoxia driven genes HIF1A , HIF2A , VEGFA and IL8 was quantified by realtime RT-PCR. Multiplex suspension array technology was used to measure the concentrations of secreted VEGF and IL8. Results The successful knockdown of HIF-1α and HIF-2α was confirmed by demonstrating considerably reduced gene expression levels of HIF1A and HIF2A by up to 71% (p=0.0222) under normoxic and hypoxic conditions. As a consequence, strongly reduced HIF-1α and HIF-2α protein levels were detected by Western blot. Targeting of HIF-1α led to a significantly decreased node formation (1.6-fold change under hypoxia, p=0.0067) with similar effects by trend on tubuli formation. The HIF-2α knockdown also led to a significantly decreased tubuli formation (1.7-fold change, p=0.0444) with similar effects by trend on node formation. Furthermore, HIF-1α targeted cells did not show any significant decrease in the gene expressions of VEGFA and IL8 but surprisingly raised cytokine levels of IL8 under hypoxia (1.4-fold change, p=0.021) compared to the control. In contrast, targeting of HIF-2α gave rise to reduced levels of secreted VEGF and IL8 with a significant suppression of IL8 gene expression under normoxia (2.1-fold change, p=0.0101). Conclusions Our findings show essential and overlapping functions of HIF-1α and HIF-2α with regard to their regulatory potential of angiogenesis in HMECs. Both transcription factors have the same impact on VEGF but differ in their effects on IL8 expression. These findings provide new insights into basic principles of angiogenesis in inflamed tissues and are therefore considered to be of clinical importance. Disclosure of Interest None Declared