tbuckley/cabot-search huggingface dataset:
Abstract C48: Antiangiogenic properties of rare earth nanoparticles: Implications in ovarian cancer
Authors: Shailendra Giri, Ramandeep Rattan, Ajay Karakoti, Sudeepta Seal, Vijayalakshmi Shridhar
Journal: Cancer Research (2009)

Abstract A substantial body of evidence suggests an association between vascular endothelial growth factor (VEGF) and the neovascularization that occurs with ovarian carcinogenesis. VEGF expression has been directly related to ascites accumulation. Phase II clinical trials in ovarian cancer using single-agent bevacizumab (a monoclonal antibody directed against VEGF) showed promising results, clearly highlighting the importance of anti-angiogenesis based-targeted therapies in ovarian cancer. One of the ways that VEGF mediates angiogenesis is by activating NADPH oxidase-ROS pathway. We have developed and engineered nanoparticles (NP) of cerium oxide (Nanoceria, NCe), a rare earth oxides, which have been tested for their ability to serve as free-radical scavengers to provide protection against chemical, biological, and radiological insults that promote the production of free radicals. Here we show for the first time that treatment of human umbilical vascular endothelial cells (HUVECs) with NCe resulted in inhibition of proliferation, capillary tube formation and VEGF165 induced activation of VEGFR2 and MMP2. Additionally, NCe treatment inhibited growth factor induced migration and invasion of ovarian cancer cells. Collectively, these results indicate that cerium oxide based NP could potentially be used as an antiangiogenic therapeutic agent in ovarian cancer. Citation Information: Cancer Res 2009;69(23 Suppl):C48.
Utilisation d'une poudre hémostatique dans les hémorragies digestives hautes d'origine tumorale ou post endoscopie thérapeutique: expérience préliminaire de l'Hémospray®
Authors: S Leblanc, A Vienne, R Coriat, JC Duchmann, M Gaudric, M Dhooge, C Pratico, S Chaussade, F Prat
Journal: Endoscopy (2013)

L'Hemospray ™ (Cook Medical) est une nouvelle méthode d'hémostase endoscopique développée récemment dans les hémorragies digestives d'origine non variqueuse (HDNV). Le principe hémostatique, lié aux hautes capacités absorbantes de la poudre inorganique, et son mode de délivrance, par aspersion à l'aide d'un cathéter, rendent son application intéressante dans les causes d'HDH réputées «difficiles» à traiter endoscopiquement. Nous rapportons l'utilisation de la poudre Hemospray™ dans les HDNV d'origine tumorale ou induites par un geste thérapeutique endoscopique.
P231 The impact of indacaterol (Onbrez®) on the daily lives and health status of patients with COPD: interim results
Authors: PW Jones, D Saralaya, JB Morjaria, T Quadrino, A Qurbain
Journal: Thorax (2013)

<h3>Introduction</h3> The GOLD guidelines recommend that the COPD Assessment Test (CAT)<sup>1</sup> can be used in guiding and optimising therapy, however there is little evidence on its use in monitoring treatment. Aim We have conducted a 6-month prospective observational study describing the impact of COPD on daily life, following the initiation of maintenance indacaterol, a once-daily long-acting beta-agonist. <h3>Method</h3> Subjects from 39 UK GP practices (April 2012 to May 2013) with a diagnosis of COPD and were newly-prescribed indacaterol for routine COPD management, either as maintenance mono-therapy or add-on therapy to long-acting muscarinic antagonists (LAMA) were recruited. Here we present interim results of completed CAT and a descriptive Daily Life Impact Questionnaire (DLIQ), developed for specifically for the study, at treatment initiation and 6–8 weeks. Further assessments will be made at 6 months, when treatment changes in addition to indacaterol will be recorded. <h3>Results</h3> One hundred and three subjects (61 males, 42 females), with a mean age of 67 years (range 44–86) and a median baseline FEV1% predicted of 61% (n = 100; IQR 51–70%) were recruited. Median time from diagnosis to indacaterol initiation was 6 months (IQR 0–37). Of the 86 (83.5%) subjects evaluated for change in CAT score, 65 (76%) had a reduction (i.e. improved health status), 18 (21%) increased and 3 (3%) remained the same (Figure 1); with a mean overall change of -4.1 (SD ± 5.6; p &lt; 0.001). Fifty-nine (69%) subjects had a ≥2 point (clinically significant) reduction in CAT score. Ninety-two patients completed the DLIQ; 42 (46%) patients reported an improved ability to perform activities important to them, which had previously been rated as being challenging (e.g. walking, gardening, housework). <h3>Conclusion</h3> The CAT appears responsive to treatment for COPD with indacaterol when assessed in routine practice and the average size of improvement was large. Alongside this mean improvement, nearly half of patients reported the ability to do more activities that previously they had found difficult. These initial results require further confirmation when full results are available at 6 months. <h3>References</h3> 1. Jones PW, Harding G, Berry P, Wiklund I, Chen WH, Kline Leidy N. Development and first validation of the COPD Assessment Test. <i>Eur Respir J</i> 2009;34:648–54
HYBRID ENDOVASCULAR REPAIR FOR THORACIC AORTIC DISEASE INVOLVING AORTIC ARCH
Authors: Myeong Gun Kim, Woong Chol Kang, Pyung Chun Oh, Eak Kyun Shin, Yae Min Park, Jeonggeun Moon, Wook-Jin Chung, Taehoon Ahn
Journal: Journal of the American College of Cardiology (2015)
A Mass Resulting From Cerebral Spinal Fluid Collection of Ventriculopleural Shunt
Authors: Yu-Yu Lu, Wan-Yu Lin, Hsin-Yi Wang, Chia-Hung Kao, Shih-Chuan Tsai
Journal: Clinical Nuclear Medicine (2013)

A 49-year-old man was brought to our hospital because of lethargy. His medical history was hydrocephalus with ventriculoperitoneal shunt initially. The ventriculoperitoneal shunt was replaced several times owing to malfunction, and it was later replaced with a right-sided ventriculopleural shunt. The chest radiograph revealed a mass at the right lung. The mass was a capsular collection of cerebral spinal fluid (CSF) in the right pleural cavity diagnosed based on radionuclide shuntogram findings.
THE LATE SODIUM CURRENT INHIBITOR GS967 SUPPRESSES SPONTANEOUS ATRIAL FIBRILLATION IN AN INTACT PORCINE MODEL
Authors: Richard L. Verrier, Juliana S. Carneiro, Afonso Alves Bento, Danilo Bacic, Bruce Nearing, Sridharan Rajamani, Luiz Belardinelli
Journal: Journal of the American College of Cardiology (2015)
THU0541 Anti-Inflammatory Activity of A Novel Small Molecule Inhibitor of Pikfvye, A Class III PI Kinase
Authors: M. Terajima, Y. Kaneko-Kobayashi, H. Mizuhara, T. Ishikawa, E. Imamura, K. Hattori, N. Nakamura, M. Yuri, Y. Higashi, N. Seki
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Aberrant production of proinflammatory cytokines is associated with various chronic inflammatory diseases, and their functional inhibition is considered beneficial. We previously reported the discovery of novel small molecule inhibitors of PIKfyve, AS2677131 and AS2795440. These compounds were found as IL-12p40 inhibitors by phenotypic screening in IFNγ/LPS-activated mouse macrophage cell line RAW264.7, but their pharmacological properties and therapeutic potential in chronic inflammation have not been fully explored. <h3>Objectives</h3> The aim of this study was to characterize <i>in vitro</i> and <i>in vivo</i> anti-inflammatory activity of a novel PIKfyve inhibitor, AS2795440. <h3>Methods</h3> <i>In vitro</i> and <i>in vivo</i> TLR ligand-induced cytokine production assays were conducted in RAW264.7 cells, mouse perioneal macrophages, and rat acute inflammation model. Concentrations of IL-12p40, IL-6, and TNFα were measured in culture supernatants or plasma by ELISA. B cell receptor (BCR)-mediated B cell activation activity was examined by measuring MHC class II expression in whole blood from rats treated with AS2795440. To evaluate therapeutic potential in chronic inflammation, rat adjuvant-induced arthritis (AIA) was examined. AS2795440 was daily administered from the day after adjuvant injection. All animal experimental procedures were approved by the Institutional Animal Care and Use Committee of Astellas Pharma Inc. <h3>Results</h3> AS2795440 inhibited the production of TLR ligand-induced proinflammatory cytokines, IL-12p40 and IL-6 but not TNFα, and expression of IgM-induced MHC class II on B cells, dose-dependently. In a rat AIA, AS2795440 (1-10 mg/kg) significantly suppressed the paw swelling and bone destruction, dose-dependently. <h3>Conclusions</h3> These results indicate that AS2795440 is a potent PIKfyve inhibitor, which has unique anti-inflammatory activity, such as inhibition of proinflammatory cytokine production and B cell activation, and has a potential therapeutic benefit in chronic inflammatory diseases. <h3>Disclosure of Interest</h3> : M. Terajima Employee of: Astellas Pharma Inc., Y. Kaneko-Kobayashi Employee of: Astellas Pharma Inc., H. Mizuhara Employee of: Astellas Pharma Inc., T. Ishikawa Employee of: Astellas Pharma Inc., E. Imamura Employee of: Astellas Pharma Inc., K. Hattori Employee of: Astellas Pharma Inc., N. Nakamura Employee of: Astellas Pharma Inc., M. Yuri Employee of: Astellas Pharma Inc., Y. Higashi Employee of: Astellas Pharma Inc., N. Seki Employee of: Astellas Pharma Inc. <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1310
Abstract 2312: A genomics approach to determining the role of DICER1 in tumorigenesis: Interferon responses in the cancer cell
Authors: Katherine B. Chiappinelli, Brian C. Haynes, Michael R. Brent, Paul J. Goodfellow
Journal: Cancer Research (2012)

Abstract DICER1 is required for generation of mature microRNAs (miRNAs) and other short noncoding RNAs. Reduced DICER1 levels are associated with adverse outcomes in a variety of cancers and multiple lines of evidence suggest DICER1 is a tumor suppressor. The effects of reduced DICER1 on mRNA transcript abundance in tumor cells remain largely unknown. To determine how reduced DICER1 levels contribute to tumor phenotypes we used shRNA to stably knock down DICER1 in endometrial cancer cell lines for extended periods (up to 25 passages). Reduced DICER1 levels had no effect on cell proliferation but were associated with enhanced cell migration and increased growth in soft agar. MiRNA profiling for the KLE cancer cell line DICER1 knockdowns (two different DICER1 shRNA constructs) revealed that miRNA levels were decreased overall. Not surprisingly, many mRNA transcripts were upregulated in the DICER1 knockdowns. A striking number of interferon stimulated genes (ISGs) showed upregulation. Upregulation of six ISG transcripts was validated by qRT-PCR in three independent knockdowns of DICER1 in KLE cells. IFNα, a key upstream regulator of the interferon response, was significantly increased in DICER1 knockdowns (KLE and additional endometrial cancer cell lines). IFNα protein secreted in media of DICER1 knockdown cells activated an interferon response in HT29 colon carcinoma cells. The majority of ISGs with increased transcript levels lacked miRNA target sequences and as such it seemed unlikely that the increase in expression levels was secondary to reduced miRNA levels. We tested the hypothesis that defects in miRNA processing could trigger an interferon response. We showed that DICER1 knockdowns in which miRNA processing is reduced have increased levels of pre-microRNAs in the cytoplasm. Pre-microRNAs are double-stranded molecules and long enough (60-100 nt) to activate the dsRNA sensors in the cytoplasm, such as Mda5/IFIH1, that typically sense viral dsRNA (&amp;gt; 30 nt) and stimulate the interferon response. Knockdown of DROSHA, necessary for processing of pri-miRNAs to pre-miRNAs, did not result in accumulation of pre-miRNAs and did not cause an interferon response. Our findings suggest elevated pre-microRNA levels trigger the interferon response to double stranded RNA (incompletely processed miRNA and other species). Rescue experiments (restoring DICER1 function) are currently underway to shed additional light on how reduced double-stranded RNA processing might elicit an interferon response. Work is ongoing to determine the relationship between the observed interferon response and the migration and soft agar phenotypes. 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 2312. doi:1538-7445.AM2012-2312
THU0346 Depressive symptoms and heart rate variability in patients with fibromyalgia
Authors: J.W. Lee, S.G. Lee, Y.E. Park, S.H. Park, J.H. Lee, S.H. Baek, G.T. Kim
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Fibromyalgia (FMS) is frequently associated with depression. Depression is a risk factor for cardiac morbidity and mortality in patients with coronary heart disease (CHD). Low heart rate variability (HRV) reflects excessive sympathetic or inadequate parasympathetic tone. Increased sympathetic or decreased parasympathetic nervous system activity predisposes patients with CHD. Little is known about whether depressive symptom in FMS is associated with reduced HRV, which is increased risk factor for CHD. <h3>Objectives</h3> To investigate the relationship between depression and HRV in patients with fibromyalgia. <h3>Methods</h3> We performed power spectral analysis on 5 minutes ECG in 130 patients with FMS between 24 and 73 years. All subjects have been evaluated with Korean version of the Fibromyalgia Impact Questionnaire (FIQ) and Beck Depression Inventory (BDI). BDI scores were classified as 3 groups: low (1-16, n=30), moderate (17-30, n=44) and severe (over 31, n=56). Very low frequency (VLF) power (0.0033 to 0.04 Hz) in ms<sup>2</sup>, which may be influenced by sympathetic and parasympathetic inputs; low frequency (LF) power (0.04 to 0.15 Hz) in ms<sup>2</sup>, which reflects both sympathetic and parasympathetic tone and is strongly associated with blood pressure regulation; and high frequency (HF) power (0.15 to 0.40 Hz) in ms<sup>2</sup>, which is modulated by respiration and primarily reflects vagal tone. <h3>Results</h3> The results of the one way ANOVA indicated that there was a difference in log-transformed High Frequency (HF) level amongst the BDI groups [F(2, 127)=3.89, p=.002]. Post-hoc comparisons using the Tukey B test indicated that severe BDI score group (3.9±1.2) has significantly lower HF level than the other BDI score groups. Low BDI score group (4.7±1.3) did not differ significantly from moderate BDI score group (4.5±1.3). There was no significant difference in VLF and LF in patients with FMS. BDI score showed negatively significant correlation with lnHF (r=-0.23, p&lt;0.01) and partial correlation coefficient of BDI score adjusted by age was -0.21 (p=0.01). <h3>Conclusions</h3> BDI scores in patients with FMS was negatively correlated with lnHF and the group with severe BDI scores showed significantly lower HF than the other BDI groups. Reduced vagal tone is associated with depressive symtoms in patients with FMS. <h3>References</h3> Carney R, Saunders R, Freedland K, Stein P, Rich M, Jaffe A. Association of depression with reduced heart rate variability in coronary artery disease. Am J Cardiol 1995;76:562-4. Staud R. Heart rate variability as a biomarker of fibromyalgia syndrome. Fut Rheumatol. 2008 Oct 1;3(5):475-483. <h3>Disclosure of Interest</h3> None Declared
Simulation of Renal Function by Tumor and Its Effect on the Calculated Glomerular Filtration Rate
Authors: IZZIE BOXEN
Journal: Clinical Nuclear Medicine (1999)

A patient with a retroperitoneal sarcoma near the left kidney was to undergo radiotherapy. Renal assessment with Tc-99m DTPA to determine renal function before radiotherapy resulted in what was thought to be a low glomerular filtration rate based on the Gates computer method and the Russell two-blood-sample method. Most likely this resulted from the observed significant accumulation of DTPA in the tumor for the first few minutes with washout for the rest of the imaging time, simulating renal function.
Successful removal of an unusual rectal foreign body with a Kocher clamp
Authors: Barış Yılmaz, Serkan Ozmete, Akif Altınbas, Bora Aktaş, Fuat Ekiz
Journal: Endoscopy (2014)

A 26-year-old man presented at our emergency department with a history of severe pelvic pain and bloating. The patient reported that he had inserted a large light bulb in his rectum about 3 hours prior to presentation. On digital rectal examination, a foreign body with an irregular surface was palpated. An X-ray image of the pelvic region revealed a large light bulb in the rectum ([Fig. 1]). Attempted manual removal of the foreign body using suprapubic pressure failed. Colonoscopy revealed that the bulb in the rectum was completely obstructing the lumen ([Fig. 2]). A polypectomy snare failed to remove it because of the bulb's round, smooth surface. The foreign body was completely removed without complication using a long Kocher clamp under colonoscopic observation and thus avoiding surgery ([Fig. 3]). Control endoscopy showed only mild superficial scratches on the rectal mucosa.
Abstract 691: <i>In vitro</i> and <i>in vivo</i> characterization of selective orally available Parp-1 inhibitors with demonstrated antitumor efficacy in BRCA negative cancer models
Authors: Gianluca Papeo, Sonia Rainoldi, Laura Gianellini, Antonella Ciavolella, Antonella Leone, Rosita Lupi, Francesco Sola, Francesco Caprera, Mauro Paolucci, Sandrine Thieffine, Rita Perego, Clara Albanese, Elena Casale, Barbara Forte, Marco Guanci, Paolo Orsini, Helena Posteri, Alessandra Scolaro, Federico Riccardi-Sirtori, Fabio Zuccotto, Daniele Donati, Jurgen Moll, Alessia Montagnoli
Journal: Cancer Research (2010)

Abstract Poly (ADP-ribose) polymerase 1 and 2 (Parp-1 and Parp-2) are nuclear enzymes responsible for signaling the presence of DNA damages by catalyzing the addition of ADP-ribose units to DNA, histones and various DNA repair enzymes, thus facilitating DNA repair. Parp-1 has been gaining increasing interest as a therapeutic target for cancer in combination with DNA damaging agents but also as single agent in particular tumor settings, such as BRCA mutated tumors. While Parp-1 knock out mice are viable and display only defects in DNA repair, double Parp-1 and Parp-2 knock-out are embryonic lethal indicating that the absence of Parp-1 and Parp-2 is less tolerated in normal cells. We confirmed this concept in vitro by RNAi of Parp-1 and Parp-2, showing that the inhibition of Parp-1 alone is enough to kill tumor cells but spares normal cells. Hence a selective Parp-1 inhibitor might have a better safety profile, particularly in view of a long treatment. Here we report the discovery and the in vitro and in vivo characterization of a novel class of potent, orally available Parp-1 selective small molecule inhibitors with no activity on other Parp isoforms such as Parp-2, −3 and −5a (tankyrase), which differentiates it from current clinical Parp inhibitors. The most potent compounds were further evaluated in vitro and in vivo. These compounds are highly potent in inhibiting DNA damage-induced Parp-1 activity in cells and exhibit selective anti-proliferative and pro-apoptotic activity in tumor cell lines harbouring defects in DNA repair. In vivo, the compounds show an excellent pharmacokinetic profile with almost complete oral bioavailability and demonstrate efficacy as a single agent in xenograft tumor models with DNA repair deficiencies superior to reference Parp inhibitors. These compounds are very well tolerated with no overt toxicity even after prolonged exposure and their mechanism of action is confirmed both in tumors and peripheral blood cells of treated mice. 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 691.
Diffusing Capacity for Carbon Monoxide as a Predictor of Gas Exchange during Exercise
Authors: Darryl Y. Sue, Ami Oren, James E. Hansen, Karlman Wasserman
Journal: New England Journal of Medicine (1987)

In patients with pulmonary disease, the diffusing capacity for carbon monoxide has been used to predict abnormal gas exchange in the lung. However, abnormal values for arterial blood gases during exercise are likely to be the most sensitive manifestations of lung disease. We compared the single-breath diffusing capacity for carbon monoxide at rest with measurements of gas exchange during exercise, including arterial oxygen tension, the alveolar-arterial difference in oxygen tension, the arterial-end-tidal difference in carbon dioxide tension, and the dead-space/tidal-volume ratio in 276 current and former shipyard workers. Sixteen workers had a diffusing capacity for carbon monoxide below 70 percent of predicted; one or more measurements of gas exchange during exercise were abnormal in 14. In contrast, of 96 men who had abnormal gas exchange during exercise, only 14 had a diffusing capacity for carbon monoxide below 70 percent of predicted. Neither the type nor the degree of abnormality in gas exchange could be predicted from the diffusing capacity. We conclude that diffusing capacity for carbon monoxide at rest is a specific but insensitive predictor of abnormal gas exchange during exercise and that, if indicated, measurements of arterial blood gases should be obtained during exercise.