tbuckley/cabot-search huggingface dataset:
Abstract 1287: Anastellin, the fibronectin-derived angiogenesis inhibitor, activates a proangiogenic signature in stromal fibroblasts
Authors: Ran You, Mingzhe Zheng, Paula J. McKeown-Longo
Journal: Cancer Research (2010)

Abstract Fibronectin is an extracellular matrix protein that is important in the regulation of angiogenesis, tumor progression and tumor metastasis. Anastellin, a peptide fragment derived from the first Type III repeat in Fibronectin (III1c), has been shown to prevent tumor angiogenesis in mouse models of human cancer and to inhibit serum-dependent growth of endothelial microvessel cells. To determine whether anastellin might have additional roles in the tumor microenvironment, we evaluated the effect of anastellin on gene expression in human dermal fibroblasts. Microarray analysis (Human Cancer PathwayFinder RT2 Profiler PCR Array) indicated that addition of anastellin to fibroblasts induced the expression of several genes including the proangiogenic inflammatory mediators, IL-8 and TNF-α. PCR analysis confirmed that expression of both TNF-α and IL-8 were markedly increased within 2 hrs suggesting a direct effect of anastellin on fibroblast gene expression. ELISA assay of the conditioned medium of anastellin treated cells indicated that the increased gene expression was accompanied by the secretion of IL-8 and TNF-α protein, which was detected between 2-4 hrs of anastellin treatment. Changes in gene expression were preceded by increased phosphorylation of c-Jun N-terminal kinase (JNK) and p38 MAPK as well as the nuclear translocation of NF-κB. PCR and ELISA analysis showed that the NF-κB inhibitor (BAY 11-7082) completely inhibited the induction of IL-8 and TNF-α. The inhibitor of p38 MAPK activity (SB 203580) and the inhibitor of JNK (SP600125) each partially attenuated the induction of IL-8 and TNFα while the combination of inhibitors completely blocked gene expression and the nuclear translocation of NF-κB in response to anastellin. Taken together, these data indicate that treatment of dermal fibroblasts with anastellin causes activation of the p38 and JNK MAPK pathways which converge downstream to promote the NF-κB dependent expression of IL-8 and TNF-α. These data suggest that fibronectin matrix remodeling induces the expression of proangiogenic cytokines by stromal cells present in the tumor microenvironment. This mechanism may represent a novel pathway of tumor resistance to angiogenesis blockade. This work is supported by NIH grant CA69612. 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 1287.
Coffee, Caffeine, and Cardiovascular Disease in Men
Authors: Diederick E. Grobbee, Eric B. Rimm, Edward Giovannucci, Graham Colditz, Meir Stampfer, Walter Willett
Journal: New England Journal of Medicine (1990)

For many years, an association between coffee consumption and the risk of coronary heart disease has been suspected. Although based on small numbers of end points, a prospective study has suggested a particularly strong association between recent coffee drinking and the incidence of cardiovascular disease.
PWE-106 Is functional sarcopenia associated with hepatic encephalopathy and severity of cirrhosis?
Authors: K Clark, D Mudrak, H Sergent, T Cross
Journal: Gut (2015)

<h3>Introduction</h3> The original Child-Turcotte score to assess stage severity of cirrhosis included an assessment of nutritional status. Loss of muscle mass (sarcopaenia) is increasingly recognised in patients with end-stage liver disease (ESLD) and skeletal muscle is recognised as a source of ammonia metabolism. The aim was to determine if there was an association with functional sarcopaenia, MELD score, hepatic encephalopathy (HE) and risk of death. <h3>Method</h3> A pilot retrospective-prospective cohort analysis of inpatients with ESLD presenting at the Royal Liverpool Hospital Between January 2014–June 2014. Patients with cirrhosis had a nutritional assessment including: BMI, hand-grip strength (HGS), biochemical assessment, MELD calculation and clinical assessment for HE. End points were to assess if there was an association with HGS with liver cirrhosis severity (MELD), HE, and death. Follow-up was completed January 2015. <h3>Results</h3> 64 patients were included in the final analysis. Male 39 (61%), median age 54 (IQR47–61 yrs). Disease aetiology was: ALD 56 (87.5%), NASH 3 (4.7%), HCV 3 (4.7%), HFE 1 (1.6%), AIH 1 (1.6%). 12 patients (19%) had HE. There were 12 deaths over the study period (19%). There was no association with HE and death on fishers exact test (p=NS). On univariate analysis the following factors were assessed for risk of death: MELD p = 0.002, Vitamin D p = 0.6, HGS p = 0,16, age p = 0.21. There was a correlation between hand grip strength and MELD (spearmans test 0=0.04), and there was also a correlation between HGS strength and HE (spearmans p = 0.03). <h3>Conclusion</h3> There is a correlation with HGS with liver disease severity and HE. No association was proven with HGS and survival in this small pilot study. HGS could be used to refine prognosis in ESLD. Large studies investigating the mechanisms and role of sarcopaenia in ESLD are required. <h3>Disclosure of interest</h3> None Declared.
BM-37 * COMPLICATIONS RELATED TO THE USE OF A VENTRICULAR DEVICE FOR THE TREATMENT OF LEPTOMENINGEAL METASTASES FROM SOLID TUMORS: A SINGLE CENTER EXPERIENCE ON 112 PATIENTS
Authors: F. Zairi, E. Le Rhun, S. Taillibert, T. Boulanger, I. Farre, J. Bonneterre, R. Assaker, M. Chamberlain
Journal: Neuro-Oncology (2014)

In Leptomeningeal Metastases (LM), short half-life agents administered by the lumbar route do not reach therapeutic ventricular concentrations resulting in negative impact on the PFS. Other advantages of intraventricular devices include less painfull procedures, certainty that the drug is well delivered. However, only a few studies have reported the complications rates and their management. Our aim was to collect prospectively the complications relative to the implantation and use of an intraventricular device in consecutive patients diagnosed with LM from solid cancer from June 2006 to December 2013. A clinical follow-up was realized every 2 weeks during 2 months and then every month. Entire CNS MRI were performed every 2-3 months. A total of 112 patients (88 women) were included. Median age was 52.5 years (range, 26-73). Primaries included breast cancer (79 patients), lung cancer (12 patients) and melanoma (6 patients). 72% of the patients received a first line of concomitant systemic and intra-CSF chemotherapy. Liposomal cytarabine was used as first line of intra-CSF treatment in all patients, except 2. The placement of the device was performed under local anesthesia. The mean operative time was 15 minutes and no complication has been reported during the procedures. During the follow-up, a total of 1046 intraventricular injections were performed. The median number of intraventricular injections per patient was 6 (range, 1-47). We observed a total of 12 complications including 7 infections (6 local infections and 1 bacterial meningitis), 2 haemorrhages, 2 leukoencephalopathy and 1 malposition. Among all, 8 complications required the removal or the replacement of the device. The complication has been considered to be the cause of the death in 2 patients. The use of an intraventricular device is an effective option, which improves the patients' comfort and compliance. An acceptable morbidity can be achieved when used in a trained team.
Abstract SY01-01: Regulation of growth by the mTOR pathway.
Authors: David M. Sabatini
Journal: Cancer Research (2013)

Abstract mTOR is the target of the immunosuppressive drug rapamycin and the central component of a nutrient-and hormone-sensitive signaling pathway that regulates cell growth and proliferation. We now appreciate that this pathway becomes deregulated in many human cancers and has an important role in the control of metabolism and aging. We have identified two distinct mTOR-containing proteins complexes, one of which regulates growth through S6K and another that regulates cell survival through Akt. These complexes, mTORC1 and mTORC2, define both rapamycin-sensitive and insensitive branches of the mTOR pathway. I will discuss new results from our lab on the regulation and functions of the mTORC1 and mTORC2 pathways. Citation Format: David M. Sabatini. Regulation of growth by the mTOR pathway. [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 SY01-01. doi:10.1158/1538-7445.AM2013-SY01-01
PMO-258 Under the microscope: a review of the management of microscopic colitis across North East England
Authors: F P Porras Perez
Journal: Gut (2012)

<h3>Introduction</h3> Microscopic colitis (MC) encompasses lymphocytic (LC) and collagenous colitis (CC) and typically presents with chronic watery diarrhoea. This retrospective review of biopsy proven cases from 5 DGH reports the clinical characteristics, possible drug precipitants, treatment and outcome in 49 cases. <h3>Methods</h3> Retrospective review of patients with histopathological confirmation of MC over a 6-month period between July 2009 and December 2009 across two FTs (5 DGHs). Demographics, clinical presentation including suspected precipitant drugs, investigations, treatment, evolution, and screening for AI diseases were collected. For patients discharged from hospital follow-up, their GPs were contacted to evaluate ongoing symptoms. <h3>Results</h3> 49 patients (38 females and 11 males) fulfilled the diagnostic criteria for MC (15 LC and 34 CC). Mean age 66 years (34–90). Mean symptom duration prior to diagnosis was 4.6 months (1–24 months). Main symptoms at the time of diagnosis; diarrhoea (100%), abdominal pain (24.4 %), weight lost (6.1%) and faecal incontinence (8.1%). Diagnosis made by flexible sigmoidoscopy (38.7%) or colonoscopy (61.3%). All patients offered clinic FU (4 DNA). Endoscopic findings reported as grossly normal in all cases. 41 patients were discharged back to GP care and 8 were under active FU in clinic. Of the 41 discharged patients, 10 had at least 1 further flare up of symptoms within 1 year of being discharged. 16 patients were treated pharmacologically: 3 with 5-ASA and 13 with oral Budesonide; 13 had an initial remission and in 6 remained symptomatic at the time of this review. 31 patients (63.26%) did not receive therapy and eight of those reported recurrent flare ups. 36 patients (73.46%) had received drugs reported to be associated with LC at some point and in 22 (61.11%) these had not been discontinued; of these, 7 (22.58%) reported at least one flare up. By registering all medications at diagnosis we found 22 patients were on PPIs, 12 patients on NSAIDs and 8 patients on SSRIs. Coeliac serology was checked in 27 patients and was positive in one patient. 12 patients (24.48%) gave a history of AI diseases. <h3>Conclusion</h3> In the absence of specific guidelines, management of MC was highly variable. Only 55.1% of cases were screened for coeliac disease and possible drug precipitants were not routinely detected and in 61.11% of cases these drugs were not discontinued. Gross endoscopic appearances were normal in all cases, reinforcing the need to take colonic biopsies in all cases of unexplained diarrhoea. While the majority of patients were discharged from follow-up, a significant number had re-attended in primary care with recurrent symptoms suggesting the disease burden may be underestimated. Specific national guidelines for the investigation, treatment and follow-up of MC would be valuable. <h3>Competing interests</h3> None declared.
AB0957 Efficacy of rebamipide in prevention of COX-2 inhibition induced gastrointestinal injuries (gastropathy) in older adults with knee osteoarthritis: A randomized placebo-controlled study
Authors: A. Abou-Raya, S. Abou-Raya, T. El Khadrawy
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Osteoarthritis (OA), particularly knee OA, represents a major cause of disability and pain. Selective COX-2 inhibitors are frequently used in the treatment of OA to control pain and inflammation. These drugs, even though associated with less upper gastrointestinal (GI) tract toxicity, still pose potential GI threats. Rebamipide, an anti-ulcer drug increases mucous and stimulates the production of prostaglandins and is frequently described as a gastroprotective agent. <h3>Objectives</h3> The aim of the present study was to assess the efficacy of combining rebamipide and celocoxib (a selective COX-2 inhibitor) versus celocoxib alone in the prevention of GI adverse threats. <h3>Methods</h3> This 12 week randomized placebo-controlled trial, allocation ratio 2:1, was designed to assess the efficacy of combination rebamipide and celocoxib (a selective COX-2 inhibitor) versus celocoxib alone in the prevention of GI adverse events in older adults with knee OA. Patients with American College of Rheumatology (ACR) clinical and radiographic criteria of primary knee OA with knee pain, [&gt;4 on the 24-hour average pain severity scale (0-10) using mean of daily ratings from week preceding randomization] for &gt;14 days/month during 3 consecutive months preceding enrolment were included in the study. Exclusion criteria included patients with GI and PUD symptoms and patients who tested positive for Helicobacter pylori. Patients were randomized into 2 groups; group 1 were given celocoxib only 200mg daily and group 2 received a combination of 200mg of celocoxib once daily and 100mg of rebamipide three times a day. The primary endpoint was endoscopic documentation of GI injury or peptic ulcer disease (PUD) after 12 weeks therapy. Symptoms of GI injury were recorded during treatment. Endoscopy was performed at baseline and after 12 weeks. Safety and tolerability were also assessed. <h3>Results</h3> Two hundred and sixty seven patients were eligible; 89 were assigned to celocoxib 200mg once daily and 178 were given a combination of 200mg of celocoxib once daily and 100mg of rebamipide three times a day. At baseline the 2 groups were similar in demographics including age, sex, duration of disease, OA severity, concomitant therapy and past history of PUD. Subjective symptoms were recorded in 41% of the rebamipide group and 79% of the celocoxib alone group, p=0.014. The incidence of gastric lesions (modified Lanza score 2 or more) was 11% in the rebamipide group compared to 38% in the celecoxib alone group, p=0.051. <h3>Conclusions</h3> Combination therapy proved to be more effective in gastroprotection than celocoxib alone for prevention of GI events. Rebamipide may thus be a suitable drug to use in the prevention of non-steroidal anti-inflammatory drug–induced gastropathy in older adults with knee OA. <h3>Disclosure of Interest</h3> None Declared
The Freedom of Medical Practice, Sterilization, and Economic Medical Philosophy
Authors: William J. Curran
Journal: New England Journal of Medicine (1978)

THE pages of the Journal have been open to controversial positions on the freedom of physicians to practice medicine as they see fit,1 particularly in the face of economic changes in medical practice and the strident claims of our day concerning a legal right to treatment by patients. In a recent column, I described a California decision that found invalid a hospital's attempt to make admission conditional upon an alleged "agreement" to arbitrate any malpractice claim.2 An earlier California case had also found that a "charitable research hospital" could not make admission conditional on the patient's signing of a release . . .
P152 Effect of obesity in patients admitted to Non invasive ventilation (NIV) Unit with acute hypercapnic respiratory failure (AHRF)
Authors: C. M. Thippanna, A. Thomas, W. Tosh, B. Chakraborty, B. Beauchamp, D. Banerjee, R. Mukherjee
Journal: Thorax (2010)

<h3>Introduction</h3> The prevalence of obesity, defined by the World Health Organization as a body mass index (BMI) greater than 30 kg/m<sup>2</sup>, is increasing in all developed countries. Obesity as the cause of admission or complicating in-patient stay has been increasing over the last decade. Obesity in intensive care unit (ICU) is significantly related to prolonged duration of mechanical ventilation and length of stay. Obesity is a known risk factor for acute hypercapnic respiratory failure (AHRF). <h3>Methods</h3> An observational, single-centre, retrospective analysis of physician diagnosed obese patients requiring NIV for AHRF between April 2005 to March 2006 and April 2009 to March 2010. Demographic data including age, sex, height, weight, date of initiating NIV and length of stay in hospital were collected and BMI was calculated. <h3>Results</h3> 154 patients were admitted in the period April 2005 to March 2006 and 160 patients in the period April 2009 to March 2010 to the dedicated NIV unit. The admissions to the unit with diagnosis of obesity in 2005–2006 and 2009–2010 are 7.14% and 15.63%, respectively. The admission rates with obesity have increased significantly in 2009–2010 compared to 2005–2006 with an OR of 2.52 (1.14 to 5.08) with a p-value of 0.021. Average length of stay in 2005–2006 is 20.6 days and in 2009–2010 19.9 days respectively. Average length of stay in non-obese patient during the same period is 8.9 days. There are a higher proportion of obese women as compared to men admitted to NIV unit in 2009–2010. Abstract P152 Table 1. <h3>Conclusion</h3> There is a significant increase in number of admissions who are obese to the NIV unit. This is consistent with the observation that there is an increase in the BMI of acute general admissions. These cohorts of obese patients have a higher average length of stay and consume enormous amount of healthcare resources. Interventions to reduce obesity in the general public need to be taken up as a priority to preserve limited healthcare resources.
Microdeletions in the Y Chromosome of Infertile Men
Authors: Jon L. Pryor, Marijo Kent-First, Ariege Muallem, Andrew H. Van Bergen, Wolfram E. Nolten, Lorraine Meisner, Kenneth P. Roberts
Journal: New England Journal of Medicine (1997)

Some infertile men with azoospermia or severe oligospermia have small deletions in regions of the Y chromosome. However, the frequency of such microdeletions among men with infertility in general is unknown. We sought to determine the prevalence of Y-chromosome microdeletions among infertile men and to correlate the clinical presentation of the men with specific deletions.We studied 200 consecutive infertile men. Each man was evaluated comprehensively for known causes of infertility, and Y-chromosome microdeletions were studied with use of the polymerase chain reaction to amplify specific regions of the chromosome. The Y chromosomes of 200 normal men were also analyzed.Fourteen infertile men (7 percent) and four normal men (2 percent) had microdeletions of the Y chromosome. Nine of the infertile men had azoospermia or severe oligospermia (sperm concentration, <5 million per milliliter), four had oligospermia (sperm concentration, 5 million to <20 million per milliliter), and one had normospermia (sperm concentration, > or = 20 million per milliliter). The size and location of the deletions varied and did not correlate with the severity of spermatogenic failure. The fathers of six infertile men with microdeletions were studied; two had the same deletions as their sons, and four had no deletions.A small proportion of men with infertility have Y-chromosome microdeletions, but the size and position of the deletions correlate poorly with the severity of spermatogenic failure, and a deletion does not preclude the presence of viable sperm and possible conception.
Abstract 3987: Merlin is a negative regulator of human melanoma
Authors: Lucas B. Murray, Ingar Lau, Qin Yu
Journal: Cancer Research (2012)

Abstract Merlin is a cytoskeletal linker protein encoded by the neurofibromatosis type 2 (NF2) gene. Like the other Band 4.1 protein family members, it serves to connect cell surface proteins to the actin cytoskeleton. Defects in the protein caused by mutations of the NF2 gene give rise to NF2 disease, which is generally characterized by the formation of bilateral vestibular schwannomas and, to a lesser extent, meningiomas and ependymomas. In addition to these tumor types, merlin has been shown to be mutated and/or merlin protein expression lost in other cancers including mesothelioma, thyroid cancers, and melanomas, albeit to a lesser extent. In the current study, we set out to elucidate the role of merlin in the progression of human melanoma. We first show that merlin knockdown enhances melanoma cell migration and invasion in vitro. Furthermore, we show that decreased merlin expression leads to increased subcutaneous melanoma growth in immuno-compromised mice. Tumors derived from merlin knockdown cells display border regions that are generally less well defined, with cases in which tumor cells are visible in the surrounding dermis and adipose tissue, which is consistent with the more invasive phenotype observed in vitro upon merlin knockdown. To compliment these knockdown experiments we overexpressed merlin in a metastatic melanoma cell line. Upon increased merlin expression, the melanoma cells exhibit decreased in vitro migration, invasion, and proliferation. These cells also display a diminished ability to form anchorage independent colonies in soft agar. Additionally, increased merlin expression inhibits in vivo subcutaneous growth of the melanoma cells in our xenograft experiments. Lastly, we surveyed several signaling pathways to identify a mechanism that exerts the negative regulatory effect of merlin on melanoma growth. We found that merlin protein levels in human melanoma cells are correlated with the extent of induced activation of the known tumor suppressors in the Hippo signaling pathway, MST1/2 Ser/Thr kinases, which have been shown to function downstream of merlin in other cell types. Taken together, these results provide evidence for the first time that merlin is a negative regulator of human melanoma progression and that it may exert its inhibitory effects through the activation of the MST1/2 kinases. 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 3987. doi:1538-7445.AM2012-3987