tbuckley/cabot-search huggingface dataset:
Abstract P5-03-03: Antitumor Activity and Cancer Stem Cells Effect of Cetuximab in Combination with Ixabepilone in Triple Negative Breast Cancers (TNBC)
Authors: T Tanei, AA Rodriguez, L Dobrolecki, DS Choi, M Landis, JC Chang
Journal: Cancer Research (2012)

Abstract Purpose: The ErbB family, including EGFR, has been demonstrated to play key roles in metastasis, tumorigenesis, cell proliferation, and drug resistance. Recently, these characteristics have been linked to a small subpopulation of cells classified as cancer stem cells (CSCs) which are believed to be responsible for tumor initiation and maintenance. Ixabepilone is the microtubule-stabilizing agent has been expected to be more sensitive than the conventional taxanes. The aim of this study was to investigate whether the EGFR monoclonocal antibody cetuximab, in combination with ixabepilone is a more effective treatment, and kill cancer stem cells more effectively as compared to chemotherapy alone in TNBC. Experimental Design and Results: Breast CSC populations were evaluated with FACS analysis (CD44+ and CD24−/low, or Aldefluor+) and mammosphere formation efficiency (MSFE). In vitro, we demonstrated that in triple negative cell lines (MDA-MB-231 and SUM159), cancer stem cell populations were decreased after treatment of cetuximab, or cetuximab plus ixabepilone. In vivo, cetuximab in combination with ixabepilone treatment caused significant tumor regression (cetuximab vs. cetuximab+ ixabepilone; tumor volume fold change P &amp;lt;0.05 (MDA-MB-231), P &amp;lt;0.0001 (SUM159) in triple negative breast cancer xenografts. Thus, cetuximab decreased CSC population in xenograft tumors. Decrease in autophagy (LC3b, p62 and autophagosomes) were seen in cetuximab-treated tumors. Conclusions: These studies demonstrate that cetuximab in combination with ixabepilone is more effective than chemotherapy alone in TNBC by affecting CSCs, as well as bulk tumor. These data support a neoadjuvant phase II study comparing ixabepilone vs. ixabepilone +cetuximab in TNBC patients. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-03-03.
907 LOW VITAMIN D SERUM LEVELS ARE ASSOCIATED WITH LIVER FIBROSIS AND IMPAIRED VIROLOGIC RESPONSE TO ANTIVIRAL THERAPY WITH PEGIFN+RBV IN HIV/HCV COINFECTED PATIENTS
Authors: M. Mandorfer, T. Reiberger, B.A. Payer, A. Ferlitsch, F. Breitenecker, M.C. Aichelburg, B. Obermayer-Pietsch, A. Rieger, M. Peck-Radosavljevic
Journal: Journal of Hepatology (2012)
Benign Intracranial Hypertension and Bell's Palsy
Authors: Abe M. Chutorian, Arnold P. Gold, Carl W. Braun
Journal: New England Journal of Medicine (1977)

Benign intracranial hypertension is associated with a variety of underlying disorders, but the pathophysiology of the process is poorly understood. We have encountered three children with benign intracranial hypertension and coexistent, otherwise typical, forms of Bell's palsy, and report this association to alert physicians to the possibility that it is not random.Case ReportsCase 1. A previously healthy 12-year-old boy complained of bifrontal headaches for one week before admission. One day before admission drooping of the left side of the face, tearing from the left eye and nausea and vomiting occurred simultaneously. He was admitted to St. Luke's Hospital . . .
NARROW BAND IMAGING COMO MÉTODO ALTERNATIVO PARA LA DETECCIÓN Y CARACTERIZACIÓN DE LOS FOCOS DE CRIPTAS ABERRANTES
Authors: M López-Cerón, M Jimeno, C Rodríguez de Miguel, M Zabalza, V Alonso-Espinaco, E Sanabria, M Cuatrecasas, J Llach, A Castells, M Pellisé
Journal: Endoscopy (2011)

Introducción: Los focos de criptas aberrantes (FCA) colónicos son grupos de criptas con crecimiento anormal identificados con cromoendoscopia (CE) que podrían ser marcadores precoces del riesgo de cáncer colorrectal (CCR). El Narrow Band Imaging (NBI) permite detectar y caracterizar cambios mucosos sutiles.
35 FINE MAPPING OF THE IL-2/IL-21 AND IL2RA LOCI IN PRIMARY SCLEROSING CHOLANGITIS
Authors: B. Srivastava, G. Mells, H. Cordell, A. Murithii, M. Brown, E. Ellinghaus, A. Franke, T.H. Karlsen, R. Sandford, G.J. Alexander, R. Chapman, S. Rushbrook, E. Melum
Journal: Journal of Hepatology (2012)
Abstract 2558: VEGF-dependent suppression of prostaglandin transporter (PGT) expression in Kras mutant human bronchial epithelial cells
Authors: Gina Lee, Brian K. Gardner, Saswati Hazra, Puja Kachroo, Mi-Heon Lee, Kostyantyn Krysan, Tonya C. Walser, Jill E. Larsen, Luc Girard, Ignacio I. Wistuba, John D. Minna, Steven M. Dubinett
Journal: Cancer Research (2012)

Abstract Prostaglandin transporters are expressed in cyclooxygenase-positive cells and provide the dominant mechanisms for transport of prostaglandins (PG) across the cell membrane. Specifically, the prostaglandin transporter PGT, expressed in many cell types including lung epithelia, is responsible for the uptake of prostaglandin E2 (PGE2) for intracellular metabolism and degradation by 15-prostaglandin dehydrogenase (15-PGDH). The regulation of prostaglandin transporters has not been fully explored in lung cancer. We hypothesize that loss of PGT expression is important in lung carcinogenesis and its loss may be enhanced in the presence of common mutations in premalignant bronchial epithelial cells and non-small cell lung cancer (NSCLC). Our preliminary studies show that PGT expression (protein and mRNA) and 15-PGDH are significantly downregulated in Kras mutant human bronchial epithelial cells (HBEC) and in NSCLC. It is well known that Kras mutant cancers are associated with increased production of VEGF, an important factor in tumor angiogenesis. In HBEC, we found significantly higher VEGF levels in Kras mutants compared to vector controls (2242 versus 628 pg/mg, p = 0.04). We proposed that VEGF modulates PGT expression and tested our hypothesis by treating HBEC and NSCLC with human recombinant VEGF. PGT expression is downregulated with exogenous VEGF treatment and neutralizing VEGF production (neutralizing VEGF antibody) prevented the loss of PGT expression. The MEK1/2 inhibitor PD98059 upregulated PGT expression in HBEC Kras. Our results suggest Kras mutation is associated with loss of PGT expression and may be dependent on VEGF production. Modulation of PGT expression may be important in lung carcinogenesis. 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 2558. doi:1538-7445.AM2012-2558
784 VIRAL KINETICS MODELING TO PREDICT cEVR AND AID IN DOSE SELECTION DECISIONS FOR PHASE-2/3 CLINICAL TRIALS
Authors: A. Agarwal, B. Zhang, H. Robison, L. Robarge, Y. Zhao, J. Fabrycki, D. Patel, G. Yang, M. Huang, J. Hui, H. Kocinsky, E. Olek, M. Deshpande
Journal: Journal of Hepatology (2013)
P5-20-01: Patient Valuation of Reduced Risk of Side Effects during Treatment for Metastatic Breast Cancer.
Authors: D Lalla, T McLaughlin, M Brammer, T Bramley, A Bare, R Carlton
Journal: Cancer Research (2011)

Abstract Background Chemotherapy treatment for metastatic breast cancer (MBC) has shown significant benefits in survival for breast cancer patients. However, chemotherapy is associated with several side effects that have a significant impact on patients’ quality of life. The objective of this analysis was to quantify the value patients with MBC place on reduced risk of treatment side effects. Methods: A willingness to pay (WTP) survey was developed to assess metastatic breast cancer patients’ willingness to pay for a reduction in the risk of breast cancer treatment side effects. The survey assessed patients’ WTP for a 25%, 50% and 100% reduction in the risk of all side effects. Patients were also asked to select the side effect they would pay the most to avoid. Additionally, the survey collected demographic information such as treatment regimen, age, race/ethnicity, region, employment status, and insurance type. Results: The survey was completed by 202 metastatic breast cancer patients. Most survey respondents were white (94%), married (62%), and over the age of 51 (78%). Most patients were covered by private insurance (67%) or Medicare (24%). Of the 58% of respondents who remembered paying out of pocket for their last treatment, the average out of pocket payment was $459. Survey respondents were willing to pay an extra $1,886, $3,837 and $7,794 for a 25%, 50% and 100% reduction in the risk of all side effects, respectively. Hair loss (28%), pain (17%) and nausea (15%) were selected most often as the side effect respondents would pay the most to avoid. Discussion: Chemotherapy for MBC is associated with several adverse events that patients would like to avoid or reduce such as hair loss, pain, nausea and neutropenia. This analysis demonstrates patients with MBC place a significant value on reducing the risk of side effects and are willing to pay 4.2 times for a treatment devoid of side effects as compared to a treatment with a 25% reduction in the risk of treatment side effects. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-20-01.
Judge rules as unlawful government plans to downgrade services at Lewisham hospital
Authors: G. Iacobucci
Journal: BMJ (2013)

England’s health secretary Jeremy Hunt acted unlawfully in announcing plans to downgrade services at Lewisham Hospital in south east London, a High Court judge has ruled.

Mr Justice Silber said that Hunt’s decision to downgrade the hospital’s accident and emergency and maternity units must be quashed because he acted outside his powers as secretary of state, and in breach of the National Health Service Act 2006.

The judge also ruled that the decision of the government appointed trust special administrator, Matthew Kershaw, to recommend the action in October last year1 was unlawful.

In January this year, the health secretary announced that he had accepted the administrator’s recommendations that a planned reconfiguration of financially stricken South London Healthcare NHS Trust should include reconfiguring NHS services across all of south east London, including neighbouring Lewisham.

Hunt announced that the emergency unit at Lewisham Hospital would not remain in its present state, and would be downgraded while still retaining …
Abstract PD04-01: Does Analysis of Disseminated Tumor Cells in Bone Marrow Give Additional Prognostic Information in Primary Breast Cancer? Analysis of Disseminated Tumor Cells in Bone Marrow — Report of a Prospective Study with 5 Years Follow-Up
Authors: A-K Falck, P-O Bendahl, C Ingvar, P Lindblom, K Lövgren, K Rennstam, M Fernö, L. Rydén
Journal: Cancer Research (2010)

Abstract Introduction: Disseminated tumor cells (DTC) in bone marrow of patients with breast cancer has, beyond the formerly known and clinically used prognostic markers, in recent publications been identified as an independent predictor of poor prognosis in patients with non-metastatic disease. Detection of DTC could therefore be a way to identify patients with an increased risk of recurrence among patients with a “good” standard prognostic profile. The present prospective study aimed to evaluate the presence and prognostic value of DTC in bone marrow in women undergoing surgery for primary breast cancer. Material and methods: From 1999 to 2003 bone marrow aspirates were obtained from the sternal crest in 569 patients during surgery for primary invasive breast cancer. Tumor cells in bone marrow were identified with cytokeratins (4,5,6,7,8,10,13,14,15,16,18,19) against epithelial cells and analyzed with immunofluorescence and immunohistochemistry. The results were related to clinical follow up for 5 years using distant disease free survival (DDFS) and breast cancer specific survival (BCSS) as end-points by uni-and multivariate analysis including standard prognostic factors. Results: Analysis of DTC were performed in 445 patients and cytokeratin positive cells were found in 159 of these (36%). The presence of DTC in bone marrow was not related to lymph node metastases (N+ 38% vs N-35%, p= 0.4), ER+/ER-(38% vs 30%, p= 0.2) or histological grade (40% grade 1; 37% grade 2; 30% grade 3, p= 0.18). BCSS was related to: lymph node engagement (+ vs -; HR 3.5, p&amp;lt; 0.001), ER (+ vs -; HR 0.55, p= 0.046), histological grade (2 vs 1: HR 4.9, p= 0.03; 3 vs 1: HR 7.4, p= 0.008), age (HR 1.02/year, p= 0.04) and tumor size (&amp;gt;20 mm vs &amp;lt;20 mm: HR 1.8, p= 0.05) in Cox multivariate analysis. Presence of DTC did not correlate either with DDFS (p= 0.97) or BCSS (p= 0.75). In the subgroup N0/ER-, a significantly higher rate of distant metastases was observed in patients with micrometastases in bone marrow (2/12 vs 0/25; p= 0.04; log rank test) and BCSS in the same subgroup was significantly related to the presence of DTC in bone marrow (2/12 vs 0/25; p= 0.04). Conclusion: Detection of micrometastases in bone marrow in primary breast cancer has previously been shown to be a significant independent predictor of poor prognosis in different studies. In a consecutive cohort including unselected patients we were not able to confirm these results. Our data suggest that it is too early to implement the method of bone marrow aspiration and diagnosis of DTC in clinical routine. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD04-01.
Revenge, even though it is not your fault
Authors: Rongjun Yu
Journal: Behavioral and Brain Sciences (2012)

Abstract McCullough et al. argue that revenge has a future-oriented function, that is, to deter future harms by changing other individuals' incentives toward the self. Recent research has shown that people seek revenge even when harms are unintentional. This commentary reports these results and proposes that revenge may also serve to reduce the immediate psychological pain resulting from unfair treatment.
TRENDS IN UTILIZATION OF SURROGATE ENDPOINTS IN CONTEMPORARY CARDIOVASCULAR CLINICAL TRIALS: A SYSTEMATIC REVIEW
Authors: Ravi Patel, Muthiah Vaduganathan, Ayman Samman-Tahhan, Andreas Kalogeropoulos, Vasiliki Georgiopoulou, Gregg Fonarow, Mihai Gheorghiade, Javed Butler
Journal: Journal of the American College of Cardiology (2016)
Two separate pathways for cerebellar LTD: NO-dependent and NO-independent
Authors: Nick A. Hartell
Journal: Behavioral and Brain Sciences (1996)

Strong stimulation of parallel fibers (PFs) leads to localized calcium influx and a long-term depression (LTD) of PF responses at the site of stimulation. These same stimuli also induce depression at spatially distant synapses to the same cell that is mediated by the diffusible messenger nitric oxide (NO). The demonstration of two distinct forms of LTD provide an explanation for the absence of the NO/cGMP pathway in cultured cells, [CBÉPEL et al.; LINDEN; VINCENT]
PWE-212 Achieving definitive haemostasis in non-variceal upper gastrointestinal bleeding—a single UK tertiary centre experience
Authors: T Chapman, G Hadley, S Dixon, A Bailey
Journal: Gut (2012)

<h3>Introduction</h3> Despite advances in endoscopic therapy for non-variceal upper gastrointestinal bleeding (NV-UGIB), achieving definitive haemostasis remains a challenge.<sup>1</sup> Radiological intervention with embolisation is an alternative to surgery where endoscopic therapy has failed, yet there is little outcome data. We describe our experience of outcome following endoscopic therapy where both radiological and surgical interventions are readily available. <h3>Methods</h3> A retrospective observational study of all patients undergoing therapeutic endoscopy as primary treatment for NV-UGIB at the John Radcliffe Hospital, Oxford, was performed. All 180 patients eligible over a 2-year period (January 2009 to December 2010) were included. The main outcome measures were failure of primary endoscopy, defined as continuing bleeding or rebleeding requiring further intervention or causing death, and definitive haemostasis rate after all intervention (repeat endoscopy, radiological embolisation or surgery). <h3>Results</h3> 180 patients underwent therapeutic endoscopy; median age 75 years, 114 male (63.3%). 128 (71.1%) had peptic ulcer disease. Haemostasis was achieved at endoscopy in 165 (91.7%). In four patients endoscopic therapy was not attempted due to inaccessibility of the lesion. There was failure of primary therapeutic endoscopy in 40 (22.2%), with continuing bleeding in 13 and rebleeding in 27. A second intervention was undertaken in 37; embolisation in 21, repeat endoscopy in 14 and surgery in 2. 13 required three or more interventions Definitive haemostasis was achieved in 18/25 (72%) of patients undergoing embolisation and 8/8 (100%) of patients undergoing surgery. All cause mortality was 20% in the embolisation group, with one patient dying from ischaemic complications. There were no deaths in the surgical group. Overall, definitive haemostasis was achieved in 174 patients (96.7%) with all cause 30-day mortality 10% and bleeding-related mortality 3.3%. Failure of primary endoscopy was associated with an increased risk in all cause mortality (RR 2.80, CI 1.18 to 6.62, p=0.02). <h3>Conclusion</h3> The failure rate of therapeutic endoscopy for NV-UGIB was comparable with the published literature. The combination of endoscopic, radiological and surgical therapy achieved definitive haemostasis in a high proportion (96.7%). When endoscopic therapy failed, interventional radiology was an effective salvage modality in the majority of cases, avoiding the need for surgery. Failure of primary endoscopic therapy was associated with all cause mortality. <h3>Competing interests</h3> None declared. <h3>Reference</h3> 1. <b>Hearnshaw SA</b>, Logan RF, Lowe D, <i>et al.</i> Acute upper gastrointestinal bleeding in the UK: patient characteristics, diagnoses and outcomes in the 2007 UK audit. <i>Gut</i> 2011;<b>60</b>:1327–35.
PTU-157 A prospective study of serum vitamin A and D levels in primary bile acid diarrhoea
Authors: I Johnston, S S Pattni, J D Nolan, T Dew, J R Walters
Journal: Gut (2012)

<h3>Introduction</h3> There is evidence that primary bile acid diarrhoea (BAD) is caused by disruption of the homeostatic mechanism controlling bile acid synthesis, with an overproduction of bile acids leading to chronic watery diarrhoea. Fibroblast Growth Factor 19 (FGF19) has been shown to be central to this homeostatic mechanism, providing negative feedback on CYP7A1, the rate limiting enzyme in bile acid synthesis. Median serum FGF19 levels have been shown to be lower in BAD patients than in diarrhoea controls. In mouse models, it has also been shown that expression of FGF15, the orthologue of FGF19, is induced by the active forms of vitamins A and D. The aim of this study was to investigate a possible causal relationship between low serum levels of vitamins A and D and BAD. <h3>Methods</h3> Patients with chronic diarrhoea were recruited prospectively. All patients underwent routine testing to exclude other causes of diarrhoea and had SeHCAT tests. Patients were classified as having primary BAD, secondary BAD, or unexplained chronic diarrhoea (CD). Serum 25OH-vitamin D was measured by LC-MS using standard procedures. Serum Vitamin A was calculated by HPLC. Results are expressed as medians. Mann–Whitney and Spearman rank correlation tests were used in analyses. <h3>Results</h3> Serum vitamin A levels were available in 145 subjects (primary BAD 46; secondary 29; CD 70). Serum vitamin D levels were available in 150 subjects (primary BAD 50; secondary 29; CD 71). There were no significant differences in the level of vitamin A between the groups with primary or secondary BAD or CD (2.10, 1.90 and 1.95 umol/l respectively, p&gt;0.05). There was no significant correlation of vitamin A with FGF19 or SeHCAT retention as a whole or within the subgroups. There were no significant differences in serum 25OH-vitamin D between the groups (38, 47, 46 nmol/l, p&gt;0.05) There was no correlation of 25OH-vitamin D with FGF19 or SeHCAT retention as a whole, or within the subgroups. <h3>Conclusion</h3> As vitamins A and D are known to induce FGF15 expression in mice, it was important to establish whether these vitamins could be associated with the abnormal FGF19 levels seen in human BAD. These results do not provide support to the possibility that deficiency of these vitamins is directly involved in the pathogenesis of BAD. <h3>Competing interests</h3> None declared.
Simultaneous Spontaneous Bicondylar Osteonecrosis of the Femur
Authors: ROBERT MANSBERG, ILIAS DRIVAS, JOHN M. ROBERTS
Journal: Clinical Nuclear Medicine (2003)

MANSBERG, ROBERT M.B.B.S., F.R.A.C.P.; DRIVAS, ILIAS M.B.B.S.; ROBERTS, JOHN M. M.B.B.S., F.R.A.C.P. Author Information
AB0271 Beneficial effect of anti-tnf therapy in the lipoprotein atherogenic risk profile in comparison with dmard standard therapy in ra patients
Authors: J. Calvo Alén, C. Baamonde, M. Agudo, T. Ruiz-Jimeno, J. Gómez-Gerique
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> RA patients portend a greater risk of cardio-vascular complications than general population. Although most probably diverse mechanisms are implicated, quantity and quality changes in the lipoproteins appear to have an important role. Anti-TNF therapy has shown important benefits in controlling the inflammatory prcess but conflicting results have been reported regarding to its effects on lipid profile. <h3>Objectives</h3> To study the effect of anti-TNF agents on the lipid and lipoprotein profile of RA patients using a comprehensive study protocol including novel and more specific parameters for this pourpue. <h3>Methods</h3> RA patients in stable treatment with anti-TNF therapy at least during the last six months and a matched (by age, gender and rheumatoid factor status) with stable doses of standard DMARDs (most of them using methotrexate) were clinically evaluated using DAS28, as activity marker and MHAQ to assess disability. In addition, a complete standard lipid profile, a comprehensive lipoprotein assessment was carried out including: Lipoprotein, and apolipoprotein A1 (ApoA1) and B ( ApoB) levels (total and lipoprotein specific), levels of paroxonase 1 (PON1), HDL, LDL, VLDL and total cholesterol, triglycerides and phospholipids levels as well as number of molecules of these lipids (mc, mt and mf respectively) in each lipoprotein, total mass (M) and number of particles (np) of the before mentioned lipoproteins, levels of PCSK9 receptor. Results of both subsets of patients were performed with standard statistical tests. <h3>Results</h3> Sixty-seven RA patients on anti-TNF and 63 matched RA patients on DMARD, mean age (58.7±12.3 and 61±12.1 years), gender distribution (81% females in both cases), disease duration (140±165 and 143±276 months) and RF status (64% in both cases) were comparable. Patients on DMARD were more active (DAS28 4.42±1.35 vs 3.57± 1.27 and hsCRP 9.4±15.2 vs 3.8±5.8 mg/l respectively. Main findings in the lipoprotein analysis are shown in table 1: <h3>Conclusions</h3> RA patients treated with anti-TNF, regardless that they show lower levels of clinical activity, they have an improvement in their atherogenic risk profile showing higher levels of ApoA1 and therefore greater antioxidant capacity as well as lower levels of total mass and number of particles of VLDL which are atherogenic risk factors. <h3>Disclosure of Interest</h3> None Declared
SEVERE RIGHT VENTRICULAR FUNCTION DETERMINED BY VISUAL ASSESSMENT IN THE CORONARY CARE UNIT SETTING PREDICTS LONG-TERM MORTALITY
Authors: Niyada Naksuk, Charat Thongprayoon, Jae Park, Sithu Win, Sunita Sharma, Prakriti Gaba, Andrew Rosenbaum, Tiffany Hu, Charles Bruce, Suraj Kapa, Samuel Asirvatham
Journal: Journal of the American College of Cardiology (2015)