tbuckley/cabot-search huggingface dataset:
Abstract 2942: EYA promotes proliferation through up-regulation of cyclin D1
Authors: Zhaoming Li, Junbo Hu, Yue Sun, Sean Li, Richard G. Pestell, Kongming Wu
Journal: Cancer Research (2011)

Abstract In Drosophila, eye development is coordinately regulated by the Retinal Determination Gene Network (RDGN), mainly consisting of dachshund (dac), eyes absent (eya), and sin oculis (so). The mammalian homologues are Dach, Eya, and Six, respectively. RDGN, although best known for its role in eye specification, is essential for the development of many organs including retinal, kidney, brain, and limb in both flies and mammals. Molecular mechanism studies support a model that Six functions as a DNA-binding factor and Dach/Eya are transcription co-factors. Eya was first characterized as a nuclear factor, interacting with Six and Dach to regulate gene expression in a context-dependent manner. Eya encodes intrinsic protein tyrosine phosphatase activity. Recently, altered expression of the DACH1/Eya/Six complex has been observed in human tumors. EYA and SIX genes are up-regulated and DACH genes are down-regulated. EYA expression was enhanced in breast, ovary and malignant peripheral nerve sheath tumors. To elucidate the function of Eya in human breast cancer and identify the down-stream targets, we established several human breast cancer cell lines (SKBr3, MDA-MB-453 and BT474) stably expressing Eya1 or phosphatase-defective mutant Eya1D327A. In all three cell lines, expression of Eya1 promoted contact-dependent and contact-independent (soft agar assay) growth. MTT assays and growth curves (cell counting) demonstrated enhanced cellular proliferation upon expression of Eya1. In contrast, cells expressing phosphatase-defective mutant Eya1D327A repressed growth were observed. Western blot analysis demonstrated increased abundance of cell Cyclin D1 in EYA1 expressing cells. Quantitative RT-PCR demonstrated about 3-fold increase of cyclin D1 mRNA abundance in MDA-MB453 cells stably expressing wild type Eya1, but not phosphatase-defective EYA1 mutant. EYA1 induced the human cyclin D1 promoter activity evaluated by luciferase assay and the EYA1 phosphatase activity was required. Immunoprecipitation studies demonstrated association of Eya1 with endogenous Six1. As EYA does not have DNA binding ability and SIX1 is known to binds to the cyclin D1 promoter, we hypothesized model in which EYA1 up-regulates SIX1, and thus a EYA1/SIX1 complex activates Cyclin D1. Lentiviral shRNAs targeting human SIX1 or cyclin D1 were transduced into EYA1 over-expressing cells respectively. The growth curve, MTT assays and clone formation results indicated the pro-proliferate effect of EYA1 was abolished by knock down the expression of either cyclin D1 or Six1. Cyclin D1 abundance was reduced by shSIX1. Taken together, our study demonstrated that cyclin D1 is a key target of EYA1. 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 2942. doi:10.1158/1538-7445.AM2011-2942
190 DE NOVO AUTO-IMMUNE HEPATITIS AND HCV RECURRENCE AFTER LIVER TRANSPLANTATION: A CHALLENGING DIAGNOSIS AND POOR PROGNOSIS
Authors: E. De Martin, A. Coilly, M. Guido, C. Mescoli, M. Sebagh, A.C. Frigo, M. Rugge, D. Samuel, J.-C. Duclos-VaUee, P. Burra
Journal: Journal of Hepatology (2012)
PREDICTION OF MODE OF DEATH IN PATIENTS WITH CHRONIC HEART FAILURE BY CARDIAC SPECT IMAGING WITH I-123 METAIODOBENZYLGUANIDINE
Authors: Yoshihiro Sato, Takahisa Yamada, Takashi Morita, Yoshio Furukawa, Shunsuke Tamaki, Yusuke Iwasaki, Masato Kawasaki, Atsushi Kikuchi, Takumi Kondo, Masatake Fukunami
Journal: Journal of the American College of Cardiology (2015)
Role of Bone Marrow Transplantation in the Disease Pathway of Myeloma
Authors: Jean-Luc Harousseau, Philippe Moreau
Journal: Journal of the National Comprehensive Cancer Network (2007)

In multiple myeloma, autologous stem cell transplantation (ASCT) has been considered a standard of care in younger patients. The introduction of novel agents (i.e., thalidomide, lenalidomide, and bortezomib) may change this scenario. These agents can be administered before or after ASCT with the goal of increasing the complete remission (CR) rate and prolonging remission. For instance, thalidomide given as maintenance therapy after double ASCT increases CR rate, event-free survival (EFS), and overall survival. Moreover, combinations of conventional chemotherapy with novel agents such as thalidomide or bortezomib yield CR rates and EFS comparable to those achieved with standard single ASCT. Prospective randomized studies are needed to evaluate the impact of novel agents versus or in combination with ASCT. Myeloablative conditioning regimens before allogeneic stem cell transplantation are being replaced with concurrent autologous-transplantation and reduced-intensity conditioning allogeneic stem cell transplantation. Transplant-related mortality associated with this procedure is lower, but more follow-up is needed before definite conclusions can be drawn.
Multicentre study highlighting clinical relevance of new high-throughput methodologies in molecular epidemiology of Pneumocystis jirovecii pneumonia
Authors: F. Esteves, B. de Sousa, E.J. Calderón, L. Huang, R. Badura, F. Maltez, Q. Bassat, Y. de Armas, F. Antunes, O. Matos
Journal: Clinical Microbiology and Infection (2016)
USE OF β-BLOCKERS IN MEDICARE BENEFICIARIES WITH SYSTOLIC HEART FAILURE AND HYPOTENSION, ASTHMA, CHRONIC OBSTRUCTIVE PULMONARY DISEASE OR PERIPHERAL VASCULAR DISEASE
Authors: Emily Levitan, Melissa K. Van Dyke, Ligong Chen, Monika Safford, Meredith Kilgore
Journal: Journal of the American College of Cardiology (2015)
Baricitinib in Patients with Refractory Rheumatoid Arthritis
Authors: Mark C. Genovese, Joel Kremer, Omid Zamani, Charles Ludivico, Marek Krogulec, Li Xie, Scott D. Beattie, Alisa E. Koch, Tracy E. Cardillo, Terence P. Rooney, William L. Macias, Stephanie de Bono, Douglas E. Schlichting, Josef S. Smolen
Journal: New England Journal of Medicine (2016)

In phase 2 studies, baricitinib, an oral Janus kinase 1 and 2 inhibitor, reduced disease activity in patients with rheumatoid arthritis who had not previously received treatment with biologic disease-modifying antirheumatic drugs (DMARDs).In this phase 3 study involving 527 patients with an inadequate response to or unacceptable side effects associated with one or more tumor necrosis factor inhibitors, other biologic DMARDs, or both, we randomly assigned the patients in a 1:1:1 ratio to baricitinib at a dose of 2 or 4 mg daily or placebo for 24 weeks. End points, tested hierarchically at week 12 to control type 1 error, were the American College of Rheumatology 20% (ACR20) response (primary end point), the Health Assessment Questionnaire-Disability Index (HAQ-DI) score, the 28-joint Disease Activity Score based on C-reactive protein level (DAS28-CRP), and a Simplified Disease Activity Index (SDAI) score of 3.3 or less (on a scale of 0.1 to 86.0, with a score of 3.3 or less indicating remission). Comparisons with placebo were made first with the 4-mg dose of baricitinib and then with the 2-mg dose.Significantly more patients receiving baricitinib at the 4-mg dose than those receiving placebo had an ACR20 response at week 12 (55% vs. 27%, P<0.001). Differences between the higher-dose baricitinib group and the placebo group were also significant for the HAQ-DI score and the DAS28-CRP but not for an SDAI score of 3.3 or less. Adverse-event rates through 24 weeks were higher for patients receiving the 2-mg dose of baricitinib and those receiving the 4-mg dose than for patients receiving placebo (71% and 77%, respectively, vs. 64%), including infections (44% and 40%, vs. 31%). The rates of serious adverse events were 4%, 10%, and 7% in the three groups, respectively. Two nonmelanoma skin cancers and two major adverse cardiovascular events, including a fatal stroke, occurred in the higher-dose group. Baricitinib was associated with a small reduction in neutrophil levels and increases in serum creatinine and low-density lipoprotein cholesterol levels.In patients with rheumatoid arthritis and an inadequate response to biologic DMARDs, baricitinib at a daily dose of 4 mg was associated with clinical improvement at 12 weeks. (Funded by Eli Lilly and Incyte; ClinicalTrials.gov number, NCT01721044.).
PTU-128 A Novel Association between Comt Gene Polymorphisms and Risk of Symptomatic Dysphagia in the Elderly: Abstract PTU-128 Table 1
Authors: D Nimmons, N Pendleton, T Payton, J Wilkinson, S Hamdy
Journal: Gut (2013)

<h3>Introduction</h3> Genetic variants of the enzyme Catechol-O-Methyl Transferase (COMT) have been associated with age related degeneration and changes in dopamine function. Further, COMT gene polymorphisms have been found to interact with other genes in affecting levels of brain plasticity. We hypothesised, given the link with dopamine and brain function, interactions between polymorphisms of the COMT gene would predict dysphagia symptoms in an elderly population. <h3>Methods</h3> 800 members of a genetically well characterised community dwelling elderly cohort received the Sydney oro-pharyngeal dysphagia questionnaire (1) via mail. A score of 180 or more was indicative of significant dysphagia. Saliva samples were assessed for COMT polymorphism carrier status. The carrier status of each polymorphism was investigated for association with dysphagia symptoms. Logistic regression analyses were performed in SPSS to investigate whether any of the polymorphisms under consideration were predictive of dysphagia after adjusting for age and gender, in addition to interaction effects between polymorphisms. <h3>Results</h3> 638 subjects (80%) returned the questionnaire, 150 were men and 488 women and the mean age was 81.2 years. Saliva samples were then analysed for 540 of these subjects and 82 (15%) of these had significant dysphagia with scores ≥180. COMT polymorphisms <i>rs165599</i> and <i>rs10835211</i> were found to be associated with dysphagia symptoms with a significant interaction between the two (p = 0.018). The effect of each of these two polymorphisms varied according to the carrier status of the other. In the case of <i>rs10835211</i>, the effect of heterozygosity was protective or harmful dependent on the respective status of <i>rs165599</i> (Table 1), with <i>rs165599</i> homozygosity producing a &gt; 400% increased risk of dysphagia. <h3>Conclusion</h3> We have found a novel relationship between self-reported symptoms of dysphagia and COMT status of polymorphisms <i>rs165599</i> and <i>rs10835211</i>. Depending on their carrier status, the odds of having dysphagia can either be increased or decreased. These results also demonstrate the importance of genetic factors in age related problems, such as dysphagia. <h3>Disclosure of Interest</h3> None Declared <h3>Reference</h3> Wallace KL, Middleton S, Cook IJ. Development and validation of a self-report symptom inventory to assess the severity of oral-pharyngeal dysphagia. Gastroenterology. 2000; 118(4):678–87.
Abstract 542: Camalexin, the phytoalexin from <i>Cruciferous Plants</i>, decreases cell proliferation and induces apoptosis in prostate cancer cells
Authors: Basil A. Smith
Journal: Cancer Research (2012)

Abstract Camalexin, the phytoalexin produced in the model plant Arabidopsis thaliana, accumulates in various cruciferous plants upon exposure to environmental stress and plant pathogens. Besides moderate antibacterial and antifungal activity, camalexin was reported to also exhibit antiproliferative and cancer chemopreventive effects. We studied the effects of camalexin treatment on viability of several prostate cancer (PCa) cell lines and whether cytostatic/cytotoxic effects of camalexin-treated prostate cancer cells were due to reactive oxygen species (ROS) generation. As models, we utilized LNCaP and its aggressive subline, C4-2, as well as ARCaP cells stably transfected with empty vector (Neo) control or constitutively active Snail cDNA that represents an EMT model. Previous studies have shown that C4-2 and ARCaP-Snail cells express more ROS than LNCaP and ARCaP-Neo, respectively. We hypothesized that camalexin would decrease cell proliferation and increase apoptosis in PCa cell lines and that the more aggressive cell lines expressing more ROS would be more sensitive to camalexin. Our results showed that camalexin treatments led to higher ROS as shown spectrofluorometrically by the oxidation of H2DCFDA, and this was decreased by co-treatment with NAC. Cell viability using MTS proliferation assay indicated that camalexin treatments decreased cell proliferation more significantly in C4-2 and ARCaP-Snail cells, as compared to LNCaP and ARCaP-Neo cells, respectively, while PrEC normal prostate epithelial cells were unaffected. Conversely, camalexin treatments increased apoptosis and mitocasp activity, which assesses caspase3/7 activity. This was associated with increased p21 and p27 anti-proliferative markers and cleaved PARP apoptotic marker as shown by western blot analysis. NAC reduced camalexin-induced ROS in ARCaP-Snail cells and abrogated camalexin-mediated cell proliferation decrease and apoptosis increase, showing that camalexin is mediating its effects through ROS. In conclusion, camalexin retarded prostate cancer cell proliferation and induced apoptosis via increased ROS generation. Interestingly, it was more potent in aggressive PCa cells expressing higher levels of ROS and did not affect normal cells. Hence, this phytoalexin has a strong potential as a novel therapeutic agent for the treatment of especially metastatic prostate cancer cells that express high levels of ROS. Supported by grants P20MD002285-01 &amp; G12RR003062-22. 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 542. doi:1538-7445.AM2012-542
PTH-193 Time to prescribe? an audit of the management of patients on parenteral nutrition
Authors: A Culkin
Journal: Gut (2015)

<h3>Introduction</h3> The Allied Health Professionals prescribing and medicines supply mechanisms scoping project report identified an evidence base for extending prescribing rights to dietitians based on improved patient safety and experience, effectiveness and value and clear clinical responsibility.<sup>1</sup>Currently at our Trust the dietitian completes the nutritional assessment and calculates requirements for patients requiring parenteral nutrition (PN) and then a doctor signs the prescription. This means that the doctor is taking legal responsibility for another healthcare professional’s assessment which has implications for patient safety. The aim of this audit was to identify who completed the nutritional assessment, calculated requirements and decided on the composition of the PN prescription and formulation and who signed the legal prescription. <h3>Method</h3> This was a point prevalence audit at a tertiary referral centre for intestinal failure. All patients receiving PN were included and a questionnaire regarding the healthcare professionals involved in the assessment and the decision regarding the prescription of the PN was completed. <h3>Results</h3> Twenty-seven patients were on PN on the day of the audit. Ten patients were on a surgical ward and 17 were on a medical ward. The initial nutritional assessment and calculation of requirements was completed by a dietitian in 100% of cases. Nine patients (33%) were considered at risk of refeeding syndrome but none developed refeeding. In 89% of cases (n = 24) the legal prescription was signed by a junior doctor. Of these 24 patients the doctor was directly involved in the patients nutritional care in only 7 cases (29%). Over the previous 7 days amendments to the PN were made by the dietitian alone (n = 14), the dietitian and doctor (n = 4), the dietitian and pharmacist (n = 2). Nineteen patients were also receiving oral diet, 2 were on trophic enteral nutrition and 6 were nil by mouth. <h3>Conclusion</h3> This audit has shown that at this tertiary referral centre the dietitian is responsible for completing the nutritional assessment and calculating requirements for patients requiring PN including the prevention of refeeding syndrome. Ongoing monitoring of the patient occurs in conjunction with other members of the nutrition team. Previous work showed a dietitian and pharmacist working together are safe to prescribe and manage PN.<sup>2</sup>Supplementary prescribing would enable dietitians to work in conjunction with pharmacists to take clinical and legal responsibility for the PN they are recommending instead of asking junior doctors to take on responsibility for their clinical decisions. This is likely to save doctors time and improve patient safety. <h3>Disclosure of interest</h3> None Declared. <h3>References</h3> Marks D. Allied Health Professionals prescribing and medicines supply mechanisms scoping project report. Department of Health, 2009 Farrer K <i>et al</i>. Pharm J 2008;280:626
Diffuse Hepatic Amebiasis Detected by FDG PET/CT
Authors: Weiyan Zhou, Jinhua Zhao, Yan Xing, Xiang Chen, Jianhua Song
Journal: Clinical Nuclear Medicine (2014)

A 39-year-old man presented with sudden decreased visual acuity in his left eye. Orbital CT and MRI revealed a soft tissue lesion in his left orbital apex. FDG PET/CT showed increased FDG uptake by the left orbital lesion, abnormal focal FDG uptake in the soft tissues of the external ears, and abnormal heterogeneous FDG activity throughout the liver. Percutaneous liver biopsy, external auditory canal discharge, and stool specimens revealed amebiasis. The patient responded to antiamebic therapy, and his lesions improved. The case demonstrates that during its early stage, hepatic amebiasis may be associated with a relatively heterogeneous pattern of FDG uptake.
OPERATIONS FOR INJURIES TO THE MEDIAN AND ULNAR NERVES.
Authors: B. BRINDLEY EADS
Journal: JAMA (1900)

It is my intention to discuss the subject entirely from its practical standpoint and to relate my personal experiences in dealing with the injuries of the median and ulnar nerves. These nerve trunks are most liable to be injured because of their exposed anatomic position on the arm; the most frequent result of violence applied directly to the nerve is complete division. Functional disturbances following incised or lacerated wounds are too often overlooked and the symptoms attributed to shock. The degree of shock in such cases is not proportionate to the size of the wound or to the degree of nerve injury. The pain following the most trifling cut will often cause extreme depression. The injured person, who already is suffering pain and is in a state of nervous expectation and dread of more pain to be caused by the stitching, is thereby frequently placed in a condition of greater
Intraoperative determination of the adequacy of myotomy length during peroral endoscopic myotomy (POEM): the double-endoscope transillumination for extent confirmation technique (DETECT)
Authors: Mouen Khashab, Vivek Kumbhari, Alba Azola, Mohamad Zein, Ahmed Messallam, Ahmed Abdelgelil, Sepideh Besharati, Anthony Kalloo, Payal Saxena
Journal: Endoscopy (2015)

<b>Background and study aims:</b> Precise identification of the gastroesophageal junction (GEJ) is a challenging prerequisite for adequate length of an esophageal myotomy. Multiple standard methods to identify the GEJ have been described; however, a more objective modality is needed to ensure effective peroral endoscopic myotomy (POEM). <b>Patients and methods:</b> In the double-endoscope transillumination for extent confirmation technique (DETECT), an ultraslim gastroscope is passed to the most distal aspect of the submucosal tunnel created during POEM. A regular gastroscope is advanced into the stomach, and the visualization of transillumination from the ultraslim gastroscope enables identification of the extent of the submucosal tunnel. <b>Results:</b> A total of 10 patients underwent POEM with DETECT. Initial submucosal tunneling was performed based on a determination of the GEJ location via standard methods. DETECT indicated the tunnel extent to be inadequate in 50 % of patients, and the tunnel was extended a further 1 to 2 cm. The mean initial tunnel length was 15.4 cm, with a mean initial myotomy length of 11.9 cm. DETECT was performed in less than 10 minutes without complications. <b>Conclusion: </b>DETECT is an objective method for determining the adequacy of the submucosal tunnel length during POEM.
NC-09 * THE IMPACT OF SUPRATOTAL RESECTION FOR GLIOBLASTOMA
Authors: T. Kitabayashi, M. Nakada, T. Furuta, K. Miyashita, M. Kinoshita, S. Tanaka, Y. Hayashi
Journal: Neuro-Oncology (2014)

Clinical benefits of supratotal resection (SR) for glioblastoma (GBM) are unclear, although SR for low-grade glioma extends overall survival (OS). We hypothesized that SR for GBM contributes to suppression of local recurrence. In this study, we investigated the clinical benefits of SR for GBM. We reviewed 21 patients with GBM (14 males, 7 females, 34-79 years old) received tumor removal with no residual tumor followed by standard adjuvant radio-chemotherapy in our hospital from 2008 through 2013. Depending on the post-operative MRI, we classified the extent of surgery into SR defined as sufficient resection beyond the margin of tumor or total resection (TR) defined as resection margins at the level of tumor border. The extent of resection (EOR) was assessed by quantifying resection cavity / tumor volume using MRI images with Brainlab iPlan software. Additionally, the information of pre/post-operative KPS, complication rate, progression free survival (PFS) and OS were collected. SR group included 5 cases (5 males, average 70.0 years old), whereas TR group included 16 cases (9 males, 7 females, average 63.6 years old). There were no significant differences in age, pre-operative KPS and methylation status of MGMT promoter. In SR group, tumor volume tended to be smaller (SR:TR = 29.2 ± 16.1cm3:39.9 ± 31.2cm3) and EOR was bigger as compared with TR group (SR:TR = 233.7 ± 34.7°:127.4 ± 21.9°). No significant difference was observed in PFS (SR:TR = median 7 months:7.5 months). However, OS tended to be shorter in SR group than in TR group (SR:TR = median 12 months:16 months). Post-operative KPS tended to be lower in SR groups. Complication rate were similar between SR and TR. Our limited data suggests no clinical benefits of SR for GBM.