tbuckley/cabot-search huggingface dataset:
Abstract 981: Study of altered metabolism due to anoikis resistance in ovarian cancer
Authors: Christine A. Caneba, Nadège Bellance, Thasni Karedath, Deepak Nagrath
Journal: Cancer Research (2011)

Abstract Cancer cells have recently been shown to be resistant to anoikis, a form of cell death due to detachment, thus decreasing responsiveness to therapy. Catecholamines, antioxidants, and oncogenes have been shown to rescue metabolic defects caused during cell detachment. Thus, there is a strong motivation to study metabolic alterations associated with anoikis resistance in cancer. Despite efforts to understand the link between anoikis and cancer metabolism, extensive metabolic analysis of cancer cells is lacking. Tissue engineering of cancer cells to create three-dimensional cell environments can also be used as a model system to study cancer metabolism. We postulate that anoikis can be regulated by metabolism in tissue engineered cultures of ovarian cancer (OC) cells. Our findings using quantification of metabolites by conducting Ultra Performance Liquid Chromatography and metabolic assays pertaining to central carbon and nitrogen metabolism provided clues as to which pathways relevant to glycolysis, the pentose phosphate pathway, the TCA and urea cycles, lipid cycle, and amino acid and nucleotide metabolisms, may be altered by anoxia in cancer cells, resulting in identification of dominant factors which regulate OC metabolism. Amino acid supplementation significantly increased the TCA cycle flux at the level of citrate synthase and the fatty acid-derived acetyl-CoA to CO2. The information we have gained elucidates the critical role of metabolism in anoikis resistance in OCC in tissue engineered cultures. 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 981. doi:10.1158/1538-7445.AM2011-981
P175 The Short Term Variability of Sputum Microbiology in Non-CF Bronchiectasis
Authors: MC Coleman, C Hennessy, D Bilton, R Wilson, MR Loebinger
Journal: Thorax (2012)

<h3>Introduction</h3> It is recommended that non-CF bronchiectasis patients have sputum cultured annually. This prospective, cohort study is the first to collect monthly cultures to assess this practise by recording the short term variability of sputum bacteriology. <h3>Method</h3> 85 patients with non-CF bronchiectasis and daily sputum production were recruited between December 2010 and May 2011. Patients completed daily symptom diaries, and spirometry and sputum samples were collected monthly for 6 months. <h3>Results</h3> 58/85 were female, average age 58 (range 17–82). Most common aetiologies were idiopathic 41/85 and post infective 19/85. 64/85 completed follow up. There were 417 sputum cultures of which only 265 cultured an organism (<i>incl. 130</i><i>Pseudomonas</i><i>aeruginosa (PA), 37 Staphlococcus aureus, 34 Haemophilus influenzae</i>.) 10/64 patients grew no organism throughout the study despite monthly samples. 30/64 had one or more positive culture for PA, including 6 patients with first isolates. Of those with positive cultures, 28/64 patients grew the same organism in all positive cultures (15/64 grew PA only) whereas 26/64 had variability in the microbe isolated. A total of 37 exacerbations occurred at time of clinic visit. Of these 4/37 were associated with growth of a pathogen not previously isolated in this patient. However, 20/37 sputum samples at the time of clinical exacerbation showed no growth despite no prior antibiotic use. 22 patients used prophylactic antibiotics of whom 14 grew PA and 2 grew no organism. 122 infective exacerbations resulted in the use of 145 antibiotics courses. 14/64 had no exacerbations over 6 months. 9/64 had one and 41/64 had two or more (median 2). Spirometry and symptom scores remained relatively stable throughout the 6 months and were not significantly different in patients with ≥2 exacerbations. <h3>Conclusion</h3> This study demonstrates the limitations of annual sputum cultures. There was significant microbe variability and importantly a significant number of first PA isolations over a short follow-up period. Furthermore, a large percentage of patients had no microbe isolated (including at exacerbation) suggesting a possible use of future molecular microbe techniques.
THU0501 Hematopoietic Stem Cell Transplantation Increases Naive and Regulatory B Cells While Decreasing Memory B Cells in Systemic Sclerosis Patients
Authors: L.C.M. Arruda, M.C. Oliveira, D.A. Moraes, D.T. Covas, J.C. Voltarelli, K.C.R. Malmegrim
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> High dose immunossuppression (HDI) followed by autologous hematopoietic stem cell transplantation (AHSCT) emerged in last past years as a therapeutic alternative for systemic sclerosis (SSc) patients [1]. The evaluation of immune reconstitution is important to elucidate the therapeutic mechanisms and improve treatment efficacy [2, 3]. <h3>Objectives</h3> To address immune reconstitution dynamics after HDI/AHSCT through quantification of regulatory T and B cells, suppressor T cells, naive and memory B cells. <h3>Methods</h3> Peripheral blood was collected from 15 diffuse SSc patients before and 6 and 12 months after transplantation. Peripheral blood mononuclear cells were immunophenotyped by flow cytometry. <h3>Results</h3> Numbers of regulatory B cells (CD19<sup>+</sup>CD24<sup>hi</sup>CD38<sup>hi</sup>) were significantly increased at 6 and 12 months post-AHSCT, compared with baseline, despite no alterations in CD4<sup>+</sup>CD25<sup>hi</sup>FoxP3<sup>+</sup> regulatory T cell numbers. Absolute counts of CD8<sup>+</sup>CD28<sup>–</sup>CD57<sup>+</sup> suppressor T cells were also significantly increased at 6 and 12 months post-therapy, when compared with the pre-treatment period. Simultaneously, numbers of CD19<sup>+</sup>CD27<sup>+</sup>IgD<sup>–</sup> memory B cells were significantly decreased at 6 and 12 months, while CD19<sup>+</sup>CD27<sup>+</sup>IgD<sup>+</sup> naive B cells transiently increased at 6 months, when compared with baseline. <h3>Conclusions</h3> Our results suggest improvement of peripheral immunoregulatory mechanisms and ablation of memory B cells after HDI/AHSCT, which may contribute to reestablishment of self-tolerance and control of autoimmunity in SSc patients. <h3>References</h3> Farge D, Labopin M, Tyndall A, Fassas A, Mancardi GL, Van Laar J, et al. Autologous hematopoietic stem cell transplantation for autoimmune diseases: an observational study on 12 years9 experience from the European Group for Blood and Marrow Transplantation Working Party on Autoimmune Diseases. Haematologica. 2010 Feb; 95(2):284-292. Farge D, Henegar C, Carmagnat M, Daneshpouy M, Marjanovic Z, Rabian C, et al. Analysis of immune reconstitution after autologous bone marrow transplantation in systemic sclerosis. Arthritis Rheum. 2005 May; 52(5):1555-1563. Tsukamoto H, Nagafuji K, Horiuchi T, Mitoma H, Niiro H, Arinobu Y, et al. Analysis of immune reconstitution after autologous CD34+ stem/progenitor cell transplantation for systemic sclerosis: predominant reconstitution of Th1 CD4+ T cells. Rheumatology (Oxford). 2011 May; 50(5):944-952. <h3>Acknowledgements</h3> Funding for this project was provided by CNPq and FAPESP. <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4148
Symptomatic Cortical Desmoids Detected on Knee SPECT
Authors: Cheolkyu Jung, Yun-Young Choi, Sukshin Cho, Kee Cheol Park
Journal: Clinical Nuclear Medicine (2002)

JUNG, CHEOLKYU M.D.,†; CHOI, YUN-YOUNG M.D.,*; CHO, SUKSHIN M.D.*; CHEOL PARK, KEE M.D.‡ Author Information
S78 Evalution of an ambulatory pleural service: costs and benefits: Abstract S78 Table 1.
Authors: RL Young, R Bhatnagar, ZD Mason, AJ Benson, CE Hooper, AO Clive, N Zahan-Evans, AJ Morley, JE Harvey, ARL Medford, NA Maskell
Journal: Thorax (2013)

<h3>Background</h3> Outpatient management of undiagnosed pleural effusions is increasing. Payment for managing these patients is usually based on standard outpatient Healthcare Resource Group (HRG) codes. For 2013/14, a new Best Practice Tariff (BPT) of £1534 has been introduced to further disincentivize emergency inpatient management. We audited our service and examined what effects this tariff may have when applied. <h3>Methods</h3> Our well-established tertiary pleural service serves a local population of around 540,000. New patients are seen in a weekly pleural clinic or in a daily respiratory admission avoidance (Hot) clinic, which had standard 2012/13 tariffs of £223 and £334 respectively. The service sees approximately 150 new effusion patients per year in clinic and 3 new patients per week in Hot. Around 50 medical thoracoscopies and 60 indwelling pleural catheter insertions are performed each year. We audited randomly selected patients from our large, prospectively-maintained database. All audited patients were seen as new pleural effusion referrals between 2008 and 2012. Diagnosis was confirmed after a minimum of 12 months' follow-up. <h3>Results</h3> 146 patients were audited. Median age 76(range 21–93), 71% male. Final diagnoses were mesothelioma (n = 28,19%), lung cancer (n = 10,7%), breast cancer (n = 13,9%), other cancer (n = 31,21%), pleural infection (n = 15,10%), benign pleuritis (n = 11,8%) and other (n = 38,26%). 92% of patients avoided direct admission following their initial clinic appointment. 115 patients (79%) underwent ultrasound-guided pleural aspiration at their initial appointment and 63(43%) patients underwent subsequent pleural biopsy. For patients with malignancy, diagnostic sensitivity on first fluid cytology was 27% (adenocarcinoma n = 15,80%; mesothelioma n = 21,5%), and 93%(25/27) for medical thoracoscopy biopsy. Histological/cytological diagnosis took a median of 20 days (IQR 10–33) from presentation. There were no significant procedural complications noted (bleeding, pneumothorax, empyema). 97%(58/60) of patients surveyed rated the service as either very good or excellent. <h3>Conclusions</h3> Ambulatory management of undiagnosed effusions is efficacious, avoids hospitalisation in the vast majority and is preferred by patients. The 2013/14 pleural effusion BPT promotes admission avoidance by encouraging appropriate outpatient management. Trust reimbursement for practising in this way should facilitate enough resource to enable new pleural services to be established where required.
Abstract 1334: Intratumoral soluble interleukin-6 receptor associated with disease progression in colorectal cancer
Authors: Yoshinaga Okugawa, Chikao Miki, Yuji Toiyama, Hiromi Yasuda, Takeshi Yokoe, Susumu Saigusa, Junichiro Hiro, Koji Tanaka, Yasuhiro Inoue, Tsutomu Nobori, Masato Kusunoki
Journal: Cancer Research (2010)

Abstract Purpose. Interleukin-6 (IL-6) binds not only to membrane form but also to soluble IL-6 receptor (sIL-6R), derived from the extracellular part of the membrane receptor. Although most soluble receptors act as functional antagonists to their cytokine, sIL-6R plays a role in agonistic activity. The aim of this study was to clarify the relationship between concentration of intra-tumoral soluble interleukin-6 receptor levels and cancer progression in colorectal cancer patients, and to clarify its kinetics with clinical outcome. Methods. We studied 161 patients undergoing surgery for colorectal cancer. We measured concentrations of sIL-6R in tumors and normal mucosa, and in supernatants from colonic cancer cell lines. Expressions of IL-6, membranous IL-6R and gp130 were evaluated by immunohistochemically Results. The net balance between the concentration of sIL-6R in cancer tissue and normal mucosa (sIL-6R Ca/N expression ratio: the cancer tissue sIL-6R concentration divided by normal mucosa sIL-6Rntration) was 1.262 ± 1.156. The decreased sIL-6R Ca/N expression ratio was significantly associated with T classification (p=0.0076), distant metastasis (p=0.0102), UICC stage (p=0.0251) and poor prognosis (p=0.0003). In Cox multivariate analysis, distant metastasis and decreased sIL-6R Ca/N expression ratio were independent risk factors for poor prognosis. Colon cancer cell lines produced sIL-6R, and the production was exaggerated by IL-1beta stimulation, and was suppressed by the addition of IL-1 receptor antagonist. Immunohistochemically, IL-6, membranous IL-6R and gp130 were intensely expressed in cancer cell specifically, and IL-6 expression in cancer cytoplasm was associated with poor prognosis (p=0.0266). The decreased levels of sIL-6R Ca/N expression ratio in cancer tissue was inversely correlated with the intense IL-6 immunoreactivity in cancer cytoplasm (p=0.0088). Conclusion: Relative decrease in sIL-6R in the tumor stroma which reflects increased IL-6/sIL-6R affinity may play a key role in the progression of colorectal carcinoma via IL-6 tran-signaling. 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 1334.
Abstract 1001: Elevated fibroblast growth factor-inducible 14 (Fn14): a novel therapeutic target in gastric cancer.
Authors: Seon-Young Kim, Oh-Hyung Kwon, Yong Sung Kim, Seung-Moo Noh, Kyung-Sang Song
Journal: Cancer Research (2013)

Abstract Chemoresistance is one of the most serious problems in the cancer treatment. Here we show that Fn14 is a gene that promotes resistance to 5-fluorouracil (5-FU) in gastric cancer. We found that 5-FU treatment augmented Fn14 expression at both the RNA and protein level in gastric cancer cell lines, and that knock-down of Fn14 using shRNA accelerated sensitivity to 5-FU. We then investigated the underlying mechanism of Fn14-mediated chemoresistance. 5-FU treatment resulted in up-regulation of Fn14 expression as well as Bcl-xL by translocation of NF-κB to the nucleus and subsequent transcriptional activation. To examine whether NF-κB binds directly to Fn14 promoter, we performed luciferase assay. As a result, 5-FU treatment augmented Fn14 promoter activity, while increased activity of Fn14 reporter gene was reduced by NF-κB inhibitor and NF-κB knock-down by siRNA. In chromatin immunoprecipitation assay, we revealed that 5-FU treatment enhanced NF-κB binding to Fn14 promoter, indicating that NF-κB activation by 5-FU was the principal event for Fn14 up-regulation followed by resistance to 5-FU in gastric cancer. Our results suggest that Fn14 is a novel therapeutic target, and that dysfunction of Fn14 combined with 5-FU treatment is an effective therapeutic strategy to overcome resistance to 5-FU of gastric cancer patients. Citation Format: Seon-Young Kim, Oh-Hyung Kwon, Yong Sung Kim, Seung-Moo Noh, Kyung-Sang Song. Elevated fibroblast growth factor-inducible 14 (Fn14): a novel therapeutic target in gastric cancer. [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 1001. doi:10.1158/1538-7445.AM2013-1001
Case of Italian mother who underwent forced caesarean is to go to High Court
Authors: C. Dyer
Journal: BMJ (2013)

A judge has criticised doctors caring for an Italian woman with bipolar disorder who was sectioned under the Mental Health Act and forced to undergo a caesarean section during a short stay in the United Kingdom.

In a judgment delivered last February but which has just been made public, Judge Roderick Newton criticised the doctors for sending her back to Italy so soon after the birth. He cast doubt on whether she had capacity to take the decision to go at the time and said that her chances of keeping her baby would have been better had she stayed in the UK and taken part in the care proceedings.1

The baby girl was born 15 months ago, but the story came to light only last weekend when a Sunday newspaper revealed the details. The 35 …
Abstract 710: Genetic identification of Annexin-A8 as a therapeutic target and prognostic marker for pancreatic cancer
Authors: Jose M. Pimiento, Dung-Tsa Chen, Barbara Centeno, Kazim Husein, Chen Wang, Anying Zhang, Mokenge P. Malafa
Journal: Cancer Research (2012)

Abstract Introduction: We previously have identified histologic grade as an important prognostic factor for outcomes in early stage pancreatic cancer following surgical resection. In this study we investigated genes associated with histologic differentiation in early stage pancreatic cancer and their biologic relevance. Methods: We studied the gene expression profile of 61 resected primary pancreatic cancers through analysis of a custom Affymetrix microarray. Significance analysis of microarrays was used to select genes associated with histologic grade. Following identification of these genes we focused on Annexin A8 (A-A8) for further mechanistic studies. We analyzed the relationship of protein expression, tumor grade and outcomes using immunohistochemistry (IHC) in a tissue microarray (TMA) of 91 resected pancreatic cancer patients. Mechanistic studies of A-Aa8 included gene silencing using SiRNA and measurement of the cellular effects by migration, proliferation and colony formation assays. Statistical analysis was performed with Fisher's exact test, T-test and ANOVA as indicated and Cox modeling was used for survival analysis. Results: We identified 34 genes that were downregulated, and 15 genes that were upregulated as tumor grade progressed from well to moderate to poorly differentiated. Then we focused on A-A8 induction in this data set, with a 5.9 fold increased A-A8 expression from low to high grade tumors (r=0.31;p=0.019), the immunohistochemical expression of A-A8 was correlated with tumor grade in a human pancreatic tumor tissue microarray (r=0.26;p=0.014); finally high expression of A-A8 is associated with a significant decrease in 5 year survival following resection of stage I and II human pancreatic cancer by Cox model (p=0.049). Western blotting confirmed increased expression of A-A8 in human pancreatic cancer cell lines. Knockdown of A-A8 in human pancreatic cancer BXPC-3 cells with SiRNA resulted in significant decrease in cell viability (p&amp;lt;0.001), cell migration (2.5 vs. 0.9mm at 96h;p=0.048), and colony formation (p=0.007). Conclusions: Studying the expression profiles of primary pancreatic cancer analyzed on Affymetrix microarrays, we identified A-A8 as a gene associated with pancreatic cancer differentiation. Downregulation of A-A8 by RNA interference in pancreatic cancer cells results in growth and migration inhibition. Finally we show that high A-A8 expression is associated with poor disease outcome in pancreatic cancer patients. These results support further investigation of Annexin A8 as a potential therapeutic target and prognostic marker for human pancreatic cancer. 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 710. doi:1538-7445.AM2012-710
Intraluminal duodenal diverticulum treated with an endoscopic procedure
Authors: K. Yamaguchi, T. Moriyama, M. Esaki, M. Gushima, S. Ayabe, S. Nakamura, T. Kitazono, T. Matsumoto
Journal: Endoscopy (2013)

A 20-year-old woman was referred to our hospital for recurrent postprandial epigastric pain and vomiting. Physical examination revealed no abdominal mass, and laboratory data were within normal limits except for slight elevation of serum amylase (301 U/l). Esophagogastroduodenoscopy identified double duodenal lumens at the inferior duodenal flexure ([Fig. 1 a]). One lumen was discovered to lead into a blind sac ([Fig. 1 b]), which was identified as a soft tissue mass in the third portion of the duodenum, covered by normal-appearing duodenal mucosa ([Fig. 1 c]). In a double contrast study of the small intestine, the blind sac was noted to be surrounded by a narrow radiolucent line, the so-called "windsock sign" ([Fig. 2]). We thus diagnosed the patient as having a pocket-type intraluminal duodenal diverticulum (IDD) [1].
Mechanisms allowing protein delivery in nasal mucosa using NPL nanoparticles
Authors: B. Bernocchi, R. Carpentier, I. Lantier, C. Ducournau, I. Dimier-Poisson, D. Betbeder
Journal: Journal of Controlled Release (2016)

The intranasal administration of proteins using nanoparticles is a promising approach for several applications, especially for mucosal vaccines. Delivery of protein within the epithelial barrier is a key point to elicit an immune response and nano-carrier has to show no toxicity. The aim of this work was to elucidate the interactions of cationic porous nanoparticles loaded with protein delivery for antigen delivery in the nose. We investigated the loading, the cellular delivery and the epithelial transcytosis of proteins associated to these nanoparticles containing an anionic lipid in their core (NPL). NPL were highly endocytosed by airway epithelial cells and significantly improved the protein delivery into the cell. In vitro transcytosis studies showed that NPL did not modify the in vitro epithelial permeability suggesting no toxicity of these carriers. Moreover protein and NPL did not translocate the epithelial barrier. In vivo studies demonstrated that NPL prolonged the nasal residence time of the protein and no NPL were found beyond the epithelial barrier in vivo , precluding a negative side effect. All together these results establish the NPL as a bio-eliminable and optimal vaccine carrier. After nasal administration, NPL deliver antigens in airway epithelial cells without crossing the epithelial barrier.
New NHS commissioning board gets to work
Authors: N. Hawkes
Journal: BMJ (2011)

The NHS Commissioning Board for England has begun work. It was established on 31 October in shadow form as a special health authority and will take on its full statutory responsibilities in April 2013, assuming that the Health and Social Care Bill passes its remaining parliamentary hurdles.

The board has a chairman, Malcolm Grant, who was nominated by the health secretary, Andrew Lansley, and approved on a 4-3 vote by the House of Commons Health Committee. The New Zealand born Professor Grant, provost of University College London, was opposed by the committee’s Labour members for failing to convince them that he was conversant with all the nooks and crannies …