tbuckley/cabot-search huggingface dataset:
Abstract 1553: Activity of new matrix metalloproteinase inhibitors designed from 3D structure
Authors: Josune Garcia-Sanmartin, Lorena de Pablo-Maiso, Jose M. Zapico, Ana Ramos, Beatriz de Pascual-Teresa, Alfredo Martinez
Journal: Cancer Research (2010)

Abstract Matrix metalloproteinases (MMPs) have been implicated in tumor development through enhancement of migration, angiogenesis, and metastasis. Therefore, MMP inhibitors (MMPIs) have been described as potential therapeutic agents for cancer treatment. However, clinical development of most MMPIs has been discontinued because of safety reasons due to their low specificity. The design of new MMPIs should pursue not only MMP blockade, but also preserving natural physiological processes that may be jeopardized by inhibition of the wrong class of MMPs. After prolonged research, only MMP1, 2, and 7 have been experimentally validated as cancer targets. On the other hand, reduction of some MMPs such as MMP3, 8, and 9 could enhance tumorigenesis and metastasis, so their inhibition should be avoided. We describe here the activity of several novel MMPIs generated by computer assisted design and chemical synthesis that present a better inhibitory profile than previous compounds. Inhibition of MMP2 and 9 activity by increasing concentrations of MMPIs was measured by gelatin zymography using human serum as the source of MMPs. The small molecules were added to the digestion buffer during an overnight incubation and zymogram bands were analyzed by densitometry. Their inhibitory activity was compared to the one elicited by 2R-[(4-biphenylsulfonyl)amino]-N-hydroxy-3-phenylpropinamide (BiPS), a commercially available MMP2/9 inhibitor. Our results show that some molecules inhibit MMP activity more strongly than BiPS, with an IC50 in the picomolar range. Specific MMP2 IC50 values of several of these small molecules were lower than the corresponding values for MMP9, presenting a promising MMP2/MMP9 inhibition ratio. These inhibitors may be the basis for future therapeutic intervention strategies in cancer.CompoundIC50 MMP2 (pM)IC50 MMP9 (pM)RATIO MMP9/MMP2Zr208741.921097.831.48Zr224&amp;gt;5.00*103&amp;gt;50.00*103-Zr2689.4751.475.44Zr3371.5414.879.67Zr3502.4511.114.53Zr3667.7513.571.75Zr36710.0232.693.26Zr3681.9114.637.67Zr369325.511549.144.76 Calculated IC50 concentrations for MMP2 and MMP9 for several novel molecules 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 1553.
RISK OF HOSPITALIZATION AMONG ADULT MEDICAID ENROLLEES WITH ATRIAL FIBRILLATION ON DIGOXIN THERAPY
Authors: Demilade Adedinsewo, Junjun Xu, Pradyumna Agasthi, Adesoji Oderinde, Nchang Taka, Oluwatoyosi Adekeye, Rajesh Sachdeva, George Rust, Anekwe Onwuanyi
Journal: Journal of the American College of Cardiology (2016)
THU0306 Predictors of outcome in a cohort of italian children/adolescents with primary raynaud’s phenomenon: A multicenter study
Authors: F. Falcini, V. Denaro, F. Cuoco, G. Martini, S. Cappelli, A. Petaccia, F. Corona, G. Carnesecchi, F. La Torre, M. Matucci Cerinic, D. Rigante
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Raynaud's phenomenon (RP) is a benign reversible vasospasm of the extremities that may occur in the absence of any underlying connective tissue disease (CTD), mostly systemic lupus erythematosus, juvenile dermatomyositis and systemic scleroderma. Predictors of a favorable outcome are still unraveled in primary RP (pRP): the causative role of various autoantibodies remain to be elucidated mostly for pRP starting in childhood or adolescence. <h3>Objectives</h3> To identify the possible predictors of outcome in a cohort of children and adolescents with pRP. <h3>Methods</h3> We performed a prospective data collection of demographic, clinical, laboratory and treatment characteristics of 76 Italian children/adolescents with pRP (54 females, 22 males, median age at disease onset: 13.3 years, median age at diagnosis: 14.7 years), managed in 4 pediatric rheumatologic centres and 1 transition clinic during the last three years. Demographic characteristics included sex, age and ethnicity. The evaluation included clinical pictures, eventual disease associations, pubertal status, laboratory data and nailfold videocapillaroscopy (NVC) at baseline and at regular 6-month-follow-up. Laboratory examinations included erythrosedimentation rate, C-reactive protein, transaminases, creatinine, hemoglobin, complement fractions C4 and C3, renal and thyroid function and specific serum autoantibodies (anti-nuclear antibodies [ANA], anti-DNAds, anti-ENA, anti-cardiolipin, anti-Scl-70 and anti-centromere antibodies). Screening for coeliac disease was performed at the first evaluation. Treatment details included the eventual specific drug used, its dosage and overall treatment duration. Out of 76, 14 patients were treated with hydroxicloroquine, 10 with calcium blockers, 1 with low-dose aspirin, 3 with iloprost, while the remaining 48 did not receive any drug.A forward stepwise multiple logistic regression analysis was used to find any association among sex, pubertal status, inflammatory parameters, NVC abnormalities, all serum autoantibodies and the risk of developing a CTD at baseline and at 36-month-follow-up. The software used was STATA 10. A <i>p</i>-value &lt;0.05 was considered significant <h3>Results</h3> ANA positivity at baseline was significantly associated with the risk of developing a CTD (<i>p</i>&lt;0.05). No NVC abnormalities was related to specific patients' outcome. No patient resulted positive at the screening for coeliac disease. <h3>Conclusions</h3> Our data show that only ANA positivity is the potential predictor of poor outcome and progression to CTD in children and adolescents with pRP. <h3>References</h3> Nigrovic PA, Fuhlbrigge RC, Sundel RP. Raynaud's phenomenon in children: a retrospective review of 123 patients. Pediatrics 2003;111:715-21. <h3>Disclosure of Interest</h3> None Declared
Late Pulmonary Sequelae of Bronchopulmonary Dysplasia
Authors: William H. Northway, Richard B. Moss, Kathryn B. Carlisle, Bruce R. Parker, Richard L. Popp, Paul T. Pitlick, Irmgard Eichler, Robert L. Lamm, Byron W. Brown
Journal: New England Journal of Medicine (1990)

Bronchopulmonary dysplasia is a chronic lung disease that often develops after mechanical ventilation in prematurely born infants with respiratory failure. It has become the most common form of chronic lung disease in infants in the United States. The long-term outcome for infants with bronchopulmonary dysplasia has not been determined.
Polyglycolic acid sheets for repair of refractory esophageal fistula
Authors: Yoshiki Tsujii, Motohiko Kato, Shinichiro Shinzaki, Atsuo Takigawa, Yoshito Hayashi, Tsutomu Nishida, Hideki Iijima, Masahiko Tsujii, Tetsuo Takehara
Journal: Endoscopy (2015)

Gastrointestinal fistulas have been treated endoscopically with various devices, but endoscopic management is occasionally difficult [1]. Here we report a case of refractory esophageal fistula successfully closed using polyglycolic acid (PGA) sheets.
A Randomized Trial of Adjuvant Chemotherapy and Immunotherapy in Cutaneous Melanoma
Authors: U. Veronesi, J. Adamus, C. Aubert, E. Bajetta, G. Beretta, G. Bonadonna, R. Bufalino, N. Cascinelli, G. Cocconi, J. Durand, J. DE Marsillac, R. L. Ikonopisov, B. Kiss, F. Lejeune, R. MacKie, G. Madej, H. Mulder, Z. Mechl, G. W. Milton, A. Morabito, H. Peter, J. Priario, E. Paul, P. Rumke, R. Sertoli, R. Tomin
Journal: New England Journal of Medicine (1982)

In a randomized trial of adjuvant chemotherapy, immunotherapy, or immunochemotherapy, 761 evaluable patients with pathological Stage II cutaneous melanoma anywhere on the body or with pathological Stage I melanoma of the trunk (Clark's level 3 to 5) were studied by the World Health Organization International Melanoma Group. Wide local excision and excisional regional lymphadenectomy alone were performed in 185 patients and the results were compared with those of surgery plus chemotherapy with dacarbazine (in 192 patients), surgery plus immunotherapy with bacille Calmette-Guérin vaccine (in 203), and surgery plus chemotherapy combined with immunotherapy (in 181). The rates of disease-free survival and overall survival at 36 months were 30.4 +/- 8.3 per cent (mean +/- S.E.) and 41.6 +/- 10.0 per cent, respectively, after surgical treatment alone; 37.2 +/- 7.9 per cent and 46.5 +/- 8.3 per cent after surgery plus chemotherapy; 34.8 +/- 7.9 per cent and 48.7 +/- 8.7 per cent after surgery plus immunotherapy; and 33.6 +/- 7.9 per cent and 50.0 +/- 8.8 per cent after surgery plus a combination of chemotherapy and immunotherapy. None of the differences between groups was significant, and thus no effect of adjuvant therapy could be demonstrated in this study.
Abstract 5419: The plant alkaloid ellipticine is detoxified by cytochrome P450 1A1/2 (CYP 1A1/2) but activated and forms DNA adducts if CYP1A1 or 1A2 is combined with cytochrome b5: an explanation for an <i>in vivo/in vitro</i> discrepancy
Authors: Eva Frei, Vera Kotrbova, Vaclav Martinek, Andrea Breuer, Marie Stiborova
Journal: Cancer Research (2011)

Abstract Ellipticine (5,11-dimethyl-6H-pyrido[4,3-b] carbazole) is an alkaloid with anti-cancer activity elicited by interfering with many cellular functions. One of these is the formation of DNA adducts upon activation by CYP or peroxidases. The metabolites responsible for detoxication or DNA adduct formation have been characterised and CYP3A1 and the othologous human enzyme CYP3A4 are the most efficient activating enzymes in microsomes from either species (Stiborová M et al. Cancer Res 64 (2004) 8374-8380). In vivo also CYP1A effectively activate ellipticine to DNA adducts, while isolated CYP1A1/2 detoxify ellipticine mainly to its 9-hydroxy derivative. Cytochrome b5 has been shown to modulate CYP catalysis by either transferring the second electron to CYPs, or by allosteric interaction thereby leading to higher CYP enzyme activity (Schenkman, J.B., I. Jansson Pharmacol. Ther. 97(2003) 139-52). Isolated cytochrome b5 was added to isolated CYP1A1 or 1A2 reconstituted with NADPH-CYP reductase in liposomes at different ratios of the three enzymes. Apo-cytochrome b5 (containing no heme) was generated in transfected E.coli (Kotrbová V. et al. Protein Expr Purif., 66(2009) 203-209) and used as such or reconstituted with heme or Mn-protoporphyrin IX. Metabolites were analysed by HPLC and UV detection and quantified with standards. DNA adducts were determined by the nuclease P1 version of the 32P-postlabeling assay. With both CYP1A1 and 1A2 the pattern of ellipticine metabolites in incubations containing cytochrome b5 shifted from detoxication to activation. This shift depended on the ratio of CYP1A to cytochrome b5 with optimal yield of 12-hydroxy- and 13-hydroxy ellipticine at a ratio of 1:5, CYP1A to cytochrome b5. The shift was more pronounced for CYP1A1 than for 1A2 leading to 6.5 fold higher DNA adduct levels than without cytochrome b5 correlating with 6 fold higher 13-hydroxy-ellipticine amounts, the metabolite responsible for the major deoxyguanosin adduct. The cytochrome b5 holo-enzyme is necessary for this effect, since neither the apo-enzyme nor the apo-enzyme reconstituted with Mn-protoporphyrin IX had the same effect. Other heme containing proteins, like myoglobin or cytochrome c had no effect. Ellipticine is, to our knowledge, the first xenobiotic compound where cytochrome b5 shifts the metabolism by CYP from detoxication to activation and DNA adduct formation. This is important also when analysing the pharmacological effects in vivo, since ellipticine induces both CYP1A and cytochrome b5. 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 5419. doi:10.1158/1538-7445.AM2011-5419
Conservative treatment of perforation following balloon dilation of the papilla after sphincterotomy
Authors: E. Voudoukis, E. Vardas, A. Theodoropoulou, A. Tavernaraki, M. Kokkinaki, K. Psillakis, K. Paraskeva, G. Paspatis
Journal: Endoscopy (2012)

In the past 2 years, we have carried out 152 consecutive cases of large balloon dilation of the papilla after full length sphincterotomy in our center. The procedure was undertaken in patients with normal structural anatomy and large (> 12 mm), unretrieved biliary duct stones, using balloon catheters (CRE Esophageal/Pyloric, maximum diameter 15, 18, or 20 mm; length 5 cm, Boston Scientific, Natick, Massachusetts, USA). We experienced three cases of perforation (2 %) related to balloon dilation during this period. All three cases involved middle-aged women hospitalized for choledocholithiasis.
A4.9 How Osteoblast Regulates Energy Metabolism and Systemic Inflammation Dependent of FRA-2 Expression
Authors: Aline Bozec, Yubin Luo, Christine Zech, Maria Jimenez, Latifa Bakiri, Mirco Petrucelli, Michael Amling, Georg Schett, Erwin Wagner
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background and Objectives</h3> The transcription factor Fra-2 (Fosl2) is a member of the AP-1 complex and an important regulator of bone homeostasis. We have previously shown that Fra-2 controls bone development, osteoclast size [1] and osteoblast differentiation through direct regulation of Collagen 1a2 and Osteocalcin (Ocn) [2]. Recent studies have established that the skeleton functions as an endocrine organ affecting metabolism through Ocn [3], although only few transcription factors and only one osteoblast-derived hormone are known to affect the crosstalk between bone and metabolism. <h3>Materials and Methods</h3> We have generated mice with specific deletion of Fra-2 (<i>Fosl2</i>) or ectopic expression of Fra-2 in osteoblast to study the role of Fra-2 beyond the bone e.g. in metabolism. <h3>Results</h3> Here we show that mice with osteoblast specific deletion of Fra-2 (<i>Fosl2</i>) have despite a low bone mass, an increased body weight. In contrast, ectopic expression of Fra-2 in osteoblasts display increased bone mass and decreased body weight accompanied with reduced serum glucose and insulin levels, improved glucose tolerance and insulin sensitivity. In addition, these Fra-2 mutant mice are protected from metabolic impairment, when challenged with high fat diet (HFD). Surprisingly a systemic inflammation and macrophage infiltration in liver, spleen and lung was observed in Fra-2 osteoblast specific mice. Mechanistically, we showed that in osteoblasts Fra-2 transcriptionally represses an important adipo-cytokine Adiponectin (Adipoq), while it induces Ocn, both responsible for the glucose and insulin metabolism alteration. Whereas, the systemic inflammation was likely due to the transcriptional increased of Osteopontin (OPN) expression by Fra-2, which is known as a potent inductor of macrophage activation. <h3>Conclusions</h3> Taking together these results show that Fra-2 expression in osteoblast transcriptionally modulates Adipoq, Ocn and OPN expression and secretion representing a novel mechanism for the endocrine function of the skeleton on systemic metabolism and inflammation. <h3>References</h3> Bozec A,<i> et al</i>, (2008). Osteoclast size is controlled by Fra-2 through LIF/LIF-receptor signalling and hypoxia. <i>Nature</i> 454(7201):221–225. Bozec A,<i> et al</i>, (2010). Fra-2/AP-1 controls bone formation by regulating osteoblast differentiation and collagen production. <i>The Journal of cell biology</i> 190(6):1093–1106. Karsenty G &amp; Ferron M (2012). The contribution of bone to whole-organism physiology. <i>Nature</i> 481(7381):314–320.
EL USO DE PROBIÓTICOS MEJORA LA CALIDAD DE LA PREPARACIÓN COLÓNICA PARA COLONOSCOPIA
Authors: D Sánchez-Muñoz, C Ortiz-Moyano, B Gómez-Rodríguez
Journal: Endoscopy (2013)

Objetivos: Estudiar si la toma de probióticos previo a la realización de colonoscopia mejora la calidad de la limpieza colónica. Pacientes y Método: Se incluyeron de forma prospectiva 211 pacientes (62 hombres/106 mujeres) que se realizaron colonoscopia en nuestra Unidad. De ellos, 52 pacientes habían tomado probióticos (Lactobacillus reuteri) al menos durante 10 días previos a la realización de la colonoscopia. La preparación colónica se realizó con picosulfato sódico/citrato magnésico. Se valoró la calidad de la limpieza colónica mediante el uso de las escalas Boston y Ottawa. Se investigó si la toma de probióticos influía en el hallazgo de pólipos. Resultados: Los resultados de ambas escalas fueron significativamente mejores en pacientes con toma de probióticos previa frente a pacientes con preparación estándar, tanto de forma global como si valoramos tramos colónicos por separado (tabla 1). No hubo diferencias en la calidad de la preparación colónica en función de edad, sexo, o turno de exploración. La mejora en la calidad de la limpieza con probióticos permitió el diagnóstico de un mayor número de pólipos, aunque sin alcanzar significación estadística.
AB0199 Effect of the level of activity on functional status in patients with early rheumatoid arthritis (ra): results from the russion «radical» cohort during a 5-year follow-up.
Authors: Y. A. Ermakova, D. E. Karateev, E. L. Luchikhina, N. V. Demidova, E. L. Nasonov
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The evolution of rheumatoid arthritis is associated with the progression of functional disorders. There are some factors, which influence on this process. Diseases activity is the main of the factors. <h3>Objectives</h3> To study the influence of the level of activity on functional status in patients with early RA for the past five years of observations. <h3>Methods</h3> We used the data of many years of the Russian prospective investigation «RADICAL» (Rheumatoid Arthritis: DIagnostic, Clinical, Aggressive Line of Treatment). In the study included 200 patients with early RA in the period from 2003 to 2007 (67.5% RF (+); 86,5% women, age of 49 [40-58]. Duration of the disease at the time was &lt; 2 years. The diagnosis of RA was established on basis of ACR criteria (1987). Patients were treated with DMARDs, including biologic therapy (24%), according the «tight-control» principle. <h3>Results</h3> With the passage of time have observed a decrease in the level of disease activity. Baseline DAS28 median [25<sup>th</sup> percentile, 75<sup>th</sup> percentile] was 5,1 [4,49-5,85]. By the fifth year of observation was 3,12 [1,86-4,32]. The same trend applies to HAQ: 1,125 [0,625-1,75], 0,75 [0,125-1,125], respectively. In the period from 1 to 4 years of follow-up was disease stabilization. However, the 5-year observation of the increase in the values of the DAS28 and HAQ. <h3>Conclusions</h3> DAS28 was positively associated with HAQ at every time point during 5 years. These results indicate, if the DAS28 is lowered, patients will benefit with better functional ability. This correlation confirms the importance of the timely suppression of disease activity in order to prevent the development of functional disorders in patients with early RA. <h3>Disclosure of Interest</h3> None Declared
Localization of Extramedullary Hematopoiesis with Tc-99m–Labeled Monoclonal Antibodies (BW 250/183)
Authors: MARC-OLIVER MOELLERS, JOCHEN BERNDT BADER, CHRISTOF ALEXANDER, SAMUEL SAMNICK, CARL-MARTIN KIRSCH
Journal: Clinical Nuclear Medicine (2002)

Extramedullary hematopoiesis is of special interest to physicians because of its relation to hematologic disease. Because it normally remains asymptomatic, sites are typically found by chance. Effective diagnosis involves a specific, reliable, whole-body and low-cost method of screening. Although radiologic methods such as computed tomography and magnetic resonance imaging can only suggest the presence of extramedullary hematopoiesis, apart from invasive and therefore risky biopsy procedures, only scintigraphy can detect and confirm the nature of hematopoietic tissue. Although radioactive tracers commonly in use partly lack the demands for specific diagnosis, Tc-99m–labeled antibodies (NCA-95) seem to combine the advantages of different scintigraphic approaches. Two patients with dyserythropoetic anemia and paravertebrally situated pelvic and thoracic tumor masses were studied for extramedullary hematopoiesis. Planar and SPECT images were obtained 6 and 24 hours after injection of 800 to 850 MBq (22 to 23 mCi) Tc-99m–labeled monoclonal antibodies (BW 250/183). In both patients, tracer accumulated in the masses, thereby revealing hematopoietic tissue. Biopsy confirmed these findings. By using Tc-99m–labeled monoclonal antibodies to detect extramedullary hematopoiesis, the demands of diagnosis were met. As an alternative to invasive diagnostic procedures, this tracer combines the advantages of other radioactive substances previously used, such as radioiron, In-111 chloride, and Tc-99m colloids. This low-cost agent is readily available and when applied, reliable, and delivers whole-body images free of additional uptake in the liver or spleen.