tbuckley/cabot-search huggingface dataset:
PWE-176 The management of perforated gastric ulcers
Authors: C Skouras, M F Leeman, S Paterson-Brown
Journal: Gut (2012)

<h3>Introduction</h3> Perforated gastric ulcers are potentially complicated surgical emergencies. Appropriate early management is essential to avoid subsequent problems including the detection of underlying malignancy. Our aim was to examine the management and outcome of patients with gastric perforations undergoing emergency laparotomy for peritonitis. <h3>Methods</h3> Patients undergoing laparotomy in the department of General Surgery for perforated gastric ulcers were identified from the prospectively maintained Lothian Surgical Audit (LSA) database over the 5-year period 2007–2011. Additional data were obtained by review of electronic records and the endoscopy reporting system (UNISOFT), in addition to reference with the South East Scotland oesophagogastric Cancer Network (SCAN) database and the histopathology laboratory Database (APEX). <h3>Results</h3> 45 patients were identified. The procedures performed were: 41 omental patch repairs (91%), two simple closures (4%) and two distal gastrectomies (4%—both for large perforations). There were four perforated gastric tumours (4%), of which two were suspected intra-operatively and confirmed histologically, one had unexpected positive histology and one had negative histology, but follow-up endoscopy confirmed carcinoma; all four were managed without resection at initial laparotomy. One of these patients underwent subsequent resection for cancer after full staging and optimisation but subsequently developed tumour recurrence and died. Median length of stay was 8 days (range 4–68). The overall inpatient mortality was 15% and there were 20 morbidities (44%; including nine respiratory complications, four wound infections and two myocardial infarctions). 33 patients had biopsies taken during surgery. Two of the remaining 12 patients had biopsies taken during postoperative endoscopy. None of the remaining 10 patients were subsequently referred with cancer. Seventeen patients in total underwent a follow-up postoperative endoscopy and 11 of them had biopsies taken. <h3>Conclusion</h3> The majority of perforated gastric ulcers can be effectively managed by laparotomy and omental patch repair. Initial biopsy and follow-up endoscopy with repeat biopsy is essential to avoid missing an underlying malignancy. <h3>Competing interests</h3> None declared.
Abstract LB-102: Inhibiting the expansion of hepatic cancer stem cells by targeting β-catenin/CBP interaction with ICG-001 in liver Pten deficient mice
Authors: Bangyan L. Stiles, Vivian Galicia, Lina He, Michael Kahn
Journal: Cancer Research (2011)

Abstract We used a liver specific Pten (phosphatase and tensin homologue deleted on chromosome ten) deletion murine model to investigate the mechanism of hepatic cancer stem cell activation in vivo. We have shown that loss of PTEN induces the transformation of liver progenitor cells to tumor initiating cells (TICs). Activation of TIC in this model involves death of hepatocytes resulting from PTEN loss induced liver steatosis. Such hepatocytes death presents a selection pressure and altered the progenitor cell niche for mutant progenitor cells to proliferate and replace liver parenchyma. We found that hepatic injury is followed by expansion of hepatic progenitors and upregulation of hepatic progenitor cell markers. In addition, we also found factors governing the progenitor niche such as Wnt ligands including Wnt5a, 7a and 10a as well as Wnt signaling receptor Fzd are induced. Furthermore, β-catenin activation is observed in vivo as well as in progenitor cells isolated from these mice. Thus, we hypothesize that activation of Wnt serves as the niche signal to allow proliferation of mutant progenitors. To test this hypothesis, we treated the isolated progenitor cells with a small molecule compound ICG-001 to interrupt b-catenin/CBP binding. β-catenin/CBP signal allows the activation of progenitor niche by inducing selfrenewal signals while inhibiting differentiation signals. We showed that ICG-001 treatment blocked the self-renewal signals and proliferation of the isolated progenitors in vitro. The in vivo experiment is ongoing and will also be presented at the meeting. Our study demonstrated that β-catenin activation, either directly through PTEN loss or indirectly through PTEN loss induced lipotoxic death of hepatocytes, serves as an important mediator for the activation of Pten mutant progenitor cells. Targeting such niche with our inhibitor may prove to be a viable approach to inhibit liver tumorigenesis. 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 LB-102. doi:10.1158/1538-7445.AM2011-LB-102
THE EFFECT OF PROCEDURAL VOLUME AND EXPERIENCE ON CLINICAL OUTCOMES AFTER TRANSCATHETER AORTIC VALVE REPLACEMENT: RESULTS FROM THE INTERNATIONAL MULTICENTER TAVR REGISTRY
Authors: Anthony Wassef, Josep Rodes-Cabau, John Webb, Antonio J. Muñoz-García, Corrado Tamburino, Antonio Dager, Vicente Serra, Ignacio Amat-Santos, Eric Dumont, Hatim Al Lawati, Sami Alnasser, Marina Urena, Marco Barbanti, Luis Benitez, Juan H. Alonso Briales, Bruno García del Blanco, Christopher Buller, Mark Peterson, Asim Cheema
Journal: Journal of the American College of Cardiology (2016)
The field effect in Barrett’s esophagus: can we use it for screening and surveillance?
Authors: Garry Farnham, Janusz Jankowski
Journal: Endoscopy (2013)

Esophageal adenocarcinoma (EAC) is a relatively uncommon but serious cancer afflicting 5 – 15 /100000 population in the UK, and in which diagnosis at the late rather than the early stage decreases the 5-year survival rates from 90 % to between 10 % and 20 % <xref idref="JR878-1">1</xref>. Barrett’s esophagus is present as a premalignant lesion in the majority of cases of EAC and although Barrett’s esophagus is a major risk factor, only 2.5 % – 5 % of cases progress to EAC. The increased risk generally initiates a program of endoscopic surveillance that enables early intervention if the disease progresses <xref idref="JR878-2">2</xref>.
Argon plasma coagulation for Barrett’s neoplasia: the right hot ingredient for a successful recipe?
Authors: Roos Pouw, Jacques Bergman
Journal: Endoscopy (2013)

Endoscopic resection has been accepted as a safe and effective treatment modality for early neoplasia in Barrett’s esophagus, and a less invasive alternative to the former gold standard of esophagectomy [1] [2] [3]. Endoscopic resection is mostly aimed at resecting focal lesions, leaving residual Barrett’s mucosa in situ. This approach, however, places the patient at risk of developing new neoplastic lesions in the remainder of the Barrett’s segment. Follow-up studies after focal endoscopic resection have demonstrated a risk of up to 30 % for the development of metachronous lesions during follow-up periods of 2 – 5 years [1] [2] [3]. To prevent secondary neoplastic lesions, ablation of the whole Barrett’s segment after focal endoscopic resection has therefore become a treatment adage [4] [5] [6].
A low-cost, sustainable, second generation system for surveillance of people living with HIV in Spain: 10-year trends in behavioural and clinical indicators, 2002 to 2011
Authors: M Diez, A Diaz, C Garriga, M Pons, A Ten, H Marcos, G Gutiérrez, S Moreno, J González-García, A M Barrios, S Arponen, M T García, M C Royo, J Toledo, G González, R Aranguren, A Izquierdo, L J Viloria, L Elizalde, E Martínez, D Castrillejo, I López, C Redondo, A Cano, collective the Hospital Survey Study Group
Journal: Eurosurveillance (2014)

A second-generation surveillance system of people infected with human immunodeficiency virus (HIV) has been implemented in Spain. Behavioural and clinical data were collected between 2002 and 2011 through an annual one-day, cross-sectional survey in public hospitals, including all in- and outpatients receiving HIVrelated care on the survey day. Mean age increased over time (from 38.7 years in 2002 to 43.8 years in 2011) and 68.4% of the 7,205 subjects were male. The proportion of migrants increased from 6.1% to 15.9%, while people who inject or used to inject drugs (PWID and Ex-PWID) decreased and men who have sex with men (MSM) and heterosexuals increased. Unprotected intercourse at last sex increased among MSM and PWID/Ex-PWID. Patients receiving antiretroviral treatment increased significantly from 76.0% to 88.2% as did those with CD4 T-cell counts ≥350 (from 48.2% to 66.9%) and viral copies <200 (from 47.0% to 85.2%). HIV-infected people with hepatitis C virus RNA decreased from 36.0% in 2004 to 29.9% in 2011, while those with HBsAg remained stable at around 4.4%. Implementation of a low-cost, sustainable system for second-generation surveillance in people living with HIV is feasible. In Spain, the information obtained has helped to define and refine public health policy and document treatment effectiveness.
Abstract LB-26: Translational up-regulation of Aurora-A in EGFR-expressed cancer
Authors: Liang-Yi Hung
Journal: Cancer Research (2010)

Abstract Abnormal expression of Aurora-A and EGFR is observed in different kinds of cancer and associated with poor prognosis in cancer patients. However, the relationship between Aurora-A and EGFR in tumor development was not clear. In previously report (Nucleic Acids Res, 2008, 36:4337-4351), we found EGFR translocates to nucleic to activate Aurora-A expression after EGF treatment in EGFR-overexpressed cells. However, we also observed that not all the EGFR-overexpressed cells have the nuclear EGFR pathway to mediate the Aurora-A expression. In this study, we demonstrated that EGF signaling increased the Aurora-A protein expression in EGFR-overexpressed colorectal cancer cell lines via increasing the translational efficiency. In addition, the overexpression of EGFR was also associated with higher expression of Aurora-A in clinical colorectal samples. Activation of the PI3K/Akt/mTOR and MEK/ERK pathways mediated the effect of EGF induced translational up-regulation. Besides, only the splicing variants containing exon 2 of Aurora-A mRNA showed increased interaction with the translational complex to synthesize Aurora-A protein under EGF stimulus. Besides, the exon 2 containing splicing variants were the major Aurora-A splicing form expressed in human colorectal cancers. Taken together, our results propose a novel regulatory mechanism for the abnormal expression of Aurora-A in EGFR-overexpressed cancers, and highlight the importance of alternative 5′-UTR splicing variants in regulating Aurora-A expression. Furthermore, the specific expression of exon 2 containing splicing variants in cancer tissues may serve as a potential target for cancer therapy in the future. 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 LB-26.
Abstract LB-109: BCR-ABL1 kinase activity but not its expression is dispensable for Ph+ quiescent stem cell survival which depends on the PP2A-controlled Jak2 activation and is sensitive to FTY720 treatment
Authors: Paolo Neviani, Jason Harb, Joshua Oaks, Christopher Walker, Ramasamy Santhanam, Carolyn Paisie, Anna Eiring, Bin Zhang, Bastianella Perazzona, Y Ma, Charlene Mao, Guido Marcucci, Tessa Holyoake, Stefano Volinia, Jorge Cortes, Michael Caligiuri, Claudia Huettner, Robert Bittman, Ching-Shih Chen, Ralph Arlinghaus, Peter Hokland, Denis-Claude Roy, Ravi Bhatia, Danilo Perrotti
Journal: Cancer Research (2011)

Abstract Background: The success of tyrosine kinase inhibitors (TKIs) depends on the addiction of Philadelphia-positive (Ph+) CML progenitors to BCR-ABL1 kinase activity. However, CML quiescent hematopoietic stem cells (HSC) are TKI-resistant and represent an active disease reservoir. We hypothesize that this innate drug-resistance depends on inhibition of the tumor suppressor protein phosphatase 2A (PP2A). PP2A can be reactivated by FTY720, a drug that targets CML but not normal progenitors. Here we investigated the mechanism controlling survival/self-renewal of quiescent leukemic HSCs and their sensitivity to PP2A-activating drugs. Methods: HSCs from CML (n=68) and healthy (n=12) donors were FACS-isolated, and the biologic importance of PP2A inhibition and pharmacologic PP2A activation on their survival/self-renewal was assessed by BM serial transplantation; CFSE and Annexin-V staining; LTC-IC and CFC/replating assays; lentiviral shRNA/cDNA-transduction; LEF/TCF and proximity-ligation assays; Western blot, confocal microscopy and FACS analyses. Results: We observed increased BCR-ABL1 expression with impaired kinase activity in quiescent CML HSCs, in which BCR-ABL1 per se is required for induction of JAK2 that subsequently activated β-catenin and inhibited PP2A. In fact, PP2A was suppressed in CML but not normal CD34+/CD38−/CD90+ HSCs. FTY720 and/or its non-immunosuppressive (S)-FTY720-OMe derivative markedly reduced survival and self-renewal of CML but not normal quiescent HSCs through BCR-ABL1 kinase-independent and PP2A-mediated JAK2 and β-catenin inhibition. Importantly, FTY720 also strongly diminished BCR-ABL1+ LT-HSC frequency in serial BM transplantation assays. Conclusions: The pharmacologic targeting of the newly-identified BCR-ABL1 kinase-independent JAK2/β-catenin interplay in quiescent HSCs with FTY720 and its derivatives, might lead to cessation of lifelong patient dependence on TKIs. 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 LB-109. doi:10.1158/1538-7445.AM2011-LB-109
A rare and potentially fatal complication of endoscopic submucosal dissection: iatrogenic type B aortic dissection
Authors: Hsiang-Ling Wu, Ying-Hsuan Tai, Ming-Chih Hou, M. Mandell, Mei-Yung Tsou
Journal: Endoscopy (2014)

Esophagus perforation occurs in 3 %– 4 % of endoscopic resections [1] [2], however, the complication of aortic dissection has not been previously reported. We present the first case in this brief report.
NPM/ALK fusion mRNA expression in Hodgkin and Reed-Sternberg cells is rare but does occur: Results from single-cell cDNA analysis
Authors: L. Trümper, H. Daus, H. Merz, F. von Bonin, U. Loftin, C. Cochlovius, P. Möller, A.C. Feller, M. Pfreundschuh
Journal: Annals of Oncology (1997)

The translocation t(2;5)(p23;q35) leads to the fusion of the nucleophosmin gene (NPM) on chromosome 5q35 to the recently described receptor kinase ALK on 2p23. It is characteristic of a subgroup of CD30+ large-cell anaplastic non-Hodgkin's lymphoma (ALCL). Since some cases of Hodgkin's disease (HD) and ALCL share common features, a common pathogenesis has been proposed in a report of the expression of NPM/ALK fusion mRNA in 11/13 Hodgkin's lymphomas.We approached this question by micro-manipulatory isolation of single Hodgkin and Reed-Sternberg (H-RS) cells and subsequent RT-PCR amplification of NPM/ALK fusion cDNA from these single cells.Specificity of cell selection was shown by the HD-specific pattern of EBV-gene expression in single H-RS cells. In 4 out of 7 cases, NPM/ALK fusion cDNA was detected in the RNA from whole lymph node tissue. In 2 out of 9 cases, NPM/ALK fusion sequences were amplified from single H-RS cells, albeit in a very low frequency (< 5%).These data indicate that NPM/ALK fusion transcripts do not play an early role in the pathogenesis of HD. Whether the rare expression of NPM/ALK is the result of clonal heterogeneity or an indication for clonal evolution and progression toward ALCL can only be answered by the repeated analysis of indicator cases during the course of the disease.
Abstract 565: An investigation into the potential therapeutic benefit of targeting Skp2 in neuroblastoma.
Authors: Laura Evans, Elaine Willmore, Deborah A. Tweddle, David R. Newell
Journal: Cancer Research (2013)

Abstract Background: S-phase kinase-associated protein 2 (Skp2) is a component of an E3 ubiquitin ligase complex which targets several key regulators of the G1/S transition of the cell cycle. Skp2 is overexpressed in many cancers and has been implicated in tumourigenesis due to its ability to degrade the cyclin-dependent kinase inhibitors p27Kip1 and p21Cip1, promote S phase entry and induce growth. We identified Skp2 as a possible MYCN target gene in neuroblastoma (Bell et al, Cell Cycle, 2007), and other groups have reported an increase in Skp2 transcript levels in aggressive MYCN- amplified neuroblastoma (Westermann et al, Clinical Cancer Res 2007). As MYCN amplification is a well-established poor prognostic marker we hypothesise that targeting Skp2 may be a potential therapeutic approach for neuroblastoma, especially the MYCN-amplified subtype. Methods: The relationship between MYCN and Skp2 was investigated using the SHEP Tet21N-regulatable MYCN expression system and Skp2 siRNA. The effects of Skp2 knockdown on downstream proteins (p21, p27), cell cycle arrest and cell apoptosis were analysed using western blotting, flow cytometry, and the caspase-3/7 glow assay, respectively. Results: A decrease in Skp2 and subsequent increase in p27 and p21 levels was seen in SHEP Tet21N cells when MYCN expression was suppressed. A G1 arrest was also induced by MYCN removal, an effect mirrored after Skp2 knockdown in Tet21N MYCN+ cells. Skp2 knockdown increased both p27 and p21 levels in non-MYCN amplified SHSY5Y cells and MYCN amplified IMR-32 cells. Both cell lines had ∼20% reduction (p&amp;lt;0.01) in growth after 72 hours knockdown compared to the scrambled control. However, only SHSY5Y cells showed a G1 arrest (p&amp;lt;0.05) and increase in caspase activity (p&amp;lt;0.05). Conclusions: These data further establish the relationship between MYCN and Skp2. The effect of Skp2 knockdown on growth arrest and apoptosis suggest it would be a valid therapeutic target in neuroblastoma. Citation Format: Laura Evans, Elaine Willmore, Deborah A. Tweddle, David R. Newell. An investigation into the potential therapeutic benefit of targeting Skp2 in neuroblastoma. [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 565. doi:10.1158/1538-7445.AM2013-565
Invasive Cervical Cancer Rising in Young White Females
Authors: N. S. Larsen
Journal: JNCI Journal of the National Cancer Institute (1994)

Journal Article Invasive Cervical Cancer Rising in Young White Females Get access Natalie S. Larsen Natalie S. Larsen Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 1, 5 January 1994, Pages 6–7, https://doi.org/10.1093/jnci/86.1.6 Published: 05 January 1994
Caractérisation des polypes coliques par la lumière blanche à haute définition et par le système électronique EPKi des endoscopes Pentax
Authors: N Chouqi, AM Marion-Audibert, L Wander, B Bancel, S Baubet, E Morineaux-Boget, JC Souquet
Journal: Endoscopy (2012)

Le système à haute définition de l'image intégré dans les endoscopes de nouvelle génération permettrait une sensibilité voisine de 85% et une spécificité de 80% pour la caractérisation des polypes. Notre objectif était d'évaluer la capacité de la lumière blanche à Haute Définition (HD) et du système électronique EPKi des endoscopes PENTAX pour classer correctement les polypes coliques en hyperplasique ou adénomateux avec dysplasie faible ou sévère.
AB0586 Role of particular class i mhc genotypes and haplotypes in determining different traits within the psoriatic arthritis phenotypes
Authors: M. Haroon, J. T. Giles, R. Winchester, O. FitzGerald
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> A rigorously ascertained psoriatic arthritis (PsA) cohort demonstrated considerable genetic heterogeneity and provided preliminary evidence that MHC genes determine quantitative traits within the PsA phenotype with different patterns of MHC effect. (Arth &amp; Rheum 2012. 64: 1134). <h3>Objectives</h3> To investigate any potential association of clinical phenotypes with already well characterised and quantified genotypes of PsA patients belonging to a genetically relatively homogeneous population <h3>Methods</h3> A consecutive cohort of 283 PsA patients underwent detailed skin and rheumatologic assessments. We chose four traits to analyze - sacroiliitis, enthesitis, joint deformity and dactylitis. To examine their genotypic interaction, we assigned a score to each patient’s allele and haplotype. +1 if an allele or haplotype was associated with a high risk for the trait, and -1 if it conferred a low risk in univariate analysis. Alleles or haplotypes not significantly associated with a trait were assigned “0”, and the score summed assuming an additive risk model. <h3>Results</h3> A total of 283 PsA patients [mean age 55±12 years; 47% male; mean PsA duration=19±9 years; 25% with sacroiliitis; 44.5% with radiographic erosions; 34% with enthesitis; 53% with dactylitis, 60% of this PsA cohort requiring TNFi therapy] were studied. The figure shows the frequency of each trait as a function of the risk score for the alleles and haplotypes associated with high or low risk and the average change in the odds of having each trait per 1 unit increase in the genotype risk score, e.g. the OR of developing enthesitis with an alleles/haplotypes genotype score of +2 to +4 was 13.9, p&lt;0.001. <h3>Image/graph</h3> <h3>Conclusions</h3> HLA genotype importantly influences the clinical phenotype of psoriatic arthritis; and these phenotypes are likely the result of cis and trans interactions of multiple individual alleles. <h3>Disclosure of Interest</h3> None Declared
Response to Letter Regarding Article, “Cardiorespiratory Fitness and Risk of Incident Atrial Fibrillation: Results From the Henry Ford Exercise Testing (FIT) Project”
Authors: Waqas T. Qureshi, Zaid Alirhayim, Michael J. Blaha, Stephen P. Juraschek, Steven J. Keteyian, Clinton A. Brawner, Mouaz H. Al-Mallah
Journal: Circulation (2015)

We thank Dr Patanè for the kind words.We agree that obstructive sleep apnea and ectopic adipose tissue deposition (eg, pericardial fat) are important risk factors for the development of atrial fibrillation (AF).Recently, both mechanisms have been suggested to have a causal effect through various paracrine and mechanical pathways.Most of our knowledge in this regard is drawn from animal models, and a recent Australian study demonstrated that overfed obese sheep with increased pericardial fat had larger atrial sizes and longer AF episodes during programmed simulation compared with lean sheep. 1 In addition, the atrial myocytes of the obese sheep had higher levels of intramyocardial fat, which was also associated with the development of AF.The profibrotic effect of epicardial fat via activin A (an adipo-fibrokine) has also been implemented in this pathway. 2Thus, the lower body weight associated with a higher level of fitness is a plausible mechanism to explain our findings.In our study, we found that the association of cardiorespiratory fitness with AF differed by level of obesity. 3 recent quasi-experimental study of 1415 individuals suggested that both weight loss and improving cardiorespiratory fitness attenuated AF recurrence. 4 Finally, atrial myocytes are affected not only by the local milieu in which they live but by a number of diverse mechanisms involving cardiac innervation.In addition, the potential pathogenic roles of anti-muscarinic receptor 2 and regulator of G-protein signaling 6 continue to be an active area of interest.We agree that future in vivo and in vitro studies should investigate whether cardiorespiratory fitness is associated with these markers and other mechanisms, an important step in developing potential future therapies.