tbuckley/cabot-search huggingface dataset:
Abstract 5313: Real-time video imaging of protease expression in vivo
Authors: Seulki Lee, Lei Zhu, James R. Mansfield, Xiaoyuan Chen
Journal: Cancer Research (2011)

Abstract Most new drug candidates generated during in vitro screening turn out to be invalid after time-consuming and costly testing in animal models. Therefore, there is an urgent need for development of noninvasive, real-time, sensitive, and cost-effective tools with high throughput for monitoring and early detection of drug efficacy in vivo. Proteases are known as exceptionally critical signaling proteins that are involved in numerous processes such as cancers. Considerable efforts have been made to identify the role of certain proteases in given biological processes and to screen specific molecules that can regulate protease expression. Most experimental methods are based on the use of protease reporters or molecular beacons. Moreover, they are limited to in vitro applications. To date, protease-activatable probes have already emerged as powerful tools for in vivo imaging because of their potential to offer high specificity and lower background. However, current activatable probes strive to image protease activity and effects in real-time. Although major improvements have been made, such as the conjugation of macromolecules to improve in vivo stability, these probes still suffer in sensitivity and specificity. In addition, conventional protease activatable probes typically take about 24 hours to activate fully, impeding real-time imaging and high throughput in in vivo applications. Here, we report a simple methodology to improve real-time imaging of protease activity by in vivo activatable probes by balancing competing needs for stability and sensitivity in applications where there are high target-to-background signal ratios. We demonstrate the first true real-time in vivo video imaging of extracellular protease expression using an ultrafast-acting and extended-use activatable probe. This simple, one-step technique is capable of boosting fluorescent signals upon target protease cleavage as early as 30 minutes from injection in a small animal model and is able to sustain the strong fluorescent signal up to 24 hours. Using this method, we video imaged the expression and inhibition of matrix metalloproteinases (MMPs) in a MMPs-positive SCC-7 tumor-bearing mouse model. The current platform can be universally applied to any target protease of interest with a known peptide substrate and is adaptable to a wide range of real-time imaging applications with high throughputs such as for in vivo drug screening, examinations of the therapeutic efficacy of drugs, and monitoring of disease onset and development in animal models. 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 5313. doi:10.1158/1538-7445.AM2011-5313
Cytotoxicity of gamma versus alpha radiation in lymphoid cell lines with defects in the TNF receptor family mediated and NF-kappa B related apoptotic and anti-apoptotic pathways
Authors: Kj Vandenbulcke, K Vandenbulcke, Rudi Beyaert, C Apostolides, T Nikula, W Janssens, Ann Janssens, Virginie de Gelder, Annick Willems, Guido Slegers, Hubert Thierens, Rudi Dierckx, Filip De Vos, Jan Philippé, Fritz Offner
Journal: Leukemia (2003)
Electrocardiographic Diagnosis of Evolving Acute Myocardial Infarction in the Presence of Left Bundle-Branch Block
Authors: Elena B. Sgarbossa, Sergio L. Pinski, Alejandro Barbagelata, Donald A. Underwood, Kathy B. Gates, Eric J. Topol, Robert M. Califf, Galen S. Wagner
Journal: New England Journal of Medicine (1996)

The presence of left bundle-branch block on the electrocardiogram may conceal the changes of acute myocardial infarction, which can delay both its recognition and treatment. We tested electrocardiographic criteria for the diagnosis of acute infarction in the presence of left bundle-branch block.
MORPHOLOGY AND COMPOSITION OF ADVANCED CORONARY PLAQUES IN HISTOLOGY PREDICT THE DELINEATION OF THE OF NAPKIN RING SIGN IN CORONARY CT ANGIOGRAPHY
Authors: Harald Seifarth, Christopher Schlett, Masataka Nakano, Fumiyuki Otsuka, Liew Gary, Pal Maurovich-Horvat, Renu Virmani, Udo Hoffmann
Journal: Journal of the American College of Cardiology (2012)
Fomepizole for the Treatment of Ethylene Glycol Poisoning
Authors: Jeffrey Brent, Kenneth McMartin, Scott Phillips, Keith K. Burkhart, J. Ward Donovan, Melanie Wells, Ken Kulig
Journal: New England Journal of Medicine (1999)

Ethylene glycol poisoning causes metabolic acidosis and renal failure and may cause death. The standard treatment is inhibition of alcohol dehydrogenase with ethanol, given in intoxicating doses, and adjunctive hemodialysis. We studied the efficacy of fomepizole, a new inhibitor of alcohol dehydrogenase, in the treatment of ethylene glycol poisoning.
IMPACT OF CEREBRAL MICROBLEEDS ON LATE SYMPTOMATIC STROKE IN PATIENTS TREATED WITH DUAL-ANTIPLATELET THERAPY AFTER DES IMPLANTATION
Authors: Yoshihiro Takeda, Shun Morishita, Suguru Kasahara, Keita Fujiwara, Yuichi Ozaki, Ryosuke Muraki, Tomoki Doue
Journal: Journal of the American College of Cardiology (2015)
Recurrent lesion of mantle cell lymphoma in the sigmoid colon detected by endoscopic autofluorescence imaging
Authors: K. Ikuta, M. Fujiya, M. Hatayama, N. Ueno, K. Moriichi, Y. Torimoto, Y. Kohgo
Journal: Endoscopy (2011)

Autofluorescence imaging (AFI) is a novel technology which captures the fluorescence emitted from the gastrointestinal tract. AFI has been reported to improve the detection rate of epithelial neoplasms in the colon [1] and be useful for differential diagnosis of gastrointestinal tract lymphoma lesions [2]. We have recently encountered a case of lymphoma in which recurrent lesions were clearly detected by AFI at quite an early stage.
News: European Drug Developers Commanding U.S. Attention
Authors: C. Vanchieri
Journal: JNCI Journal of the National Cancer Institute (1993)

Journal Article News: European Drug Developers Commanding U.S. Attention Get access Cori Vanchieri Cori Vanchieri Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 85, Issue 15, 4 August 1993, Pages 1192–1194, https://doi.org/10.1093/jnci/85.15.1192 Published: 04 August 1993
Transcatheter aortic valve replacement versus surgical valve replacement in intermediate-risk patients: a propensity score analysis
Authors: Vinod H Thourani, Susheel Kodali, Raj R Makkar, Howard C Herrmann, Mathew Williams, Vasilis Babaliaros, Richard Smalling, Scott Lim, S Chris Malaisrie, Samir Kapadia, Wilson Y Szeto, Kevin L Greason, Dean Kereiakes, Gorav Ailawadi, Brian K Whisenant, Chandan Devireddy, Jonathon Leipsic, Rebecca T Hahn, Philippe Pibarot, Neil J Weissman, Wael A Jaber, David J Cohen, Rakesh Suri, E Murat Tuzcu, Lars G Svensson, John G Webb, Jeffrey W Moses, Michael J Mack, D Craig Miller, Craig R Smith, Maria C Alu, Rupa Parvataneni, Ralph B D'Agostino, Martin B Leon
Journal: The Lancet (2016)
Intracranial Efficacy of Crizotinib Versus Chemotherapy in Patients With Advanced <i>ALK</i>-Positive Non–Small-Cell Lung Cancer: Results From PROFILE 1014
Authors: Benjamin J. Solomon, Federico Cappuzzo, Enriqueta Felip, Fiona H. Blackhall, Daniel B. Costa, Dong-Wan Kim, Kazuhiko Nakagawa, Yi-Long Wu, Tarek Mekhail, Jolanda Paolini, Jennifer Tursi, Tiziana Usari, Keith D. Wilner, Paulina Selaru, Tony S.K. Mok
Journal: Journal of Clinical Oncology (2016)

Purpose Intracranial efficacy of first-line crizotinib versus chemotherapy was compared prospectively in the phase III PROFILE 1014 study in ALK-positive non–small-cell lung cancer. Patients and Methods Patients were randomly assigned to receive crizotinib (250 mg twice daily; n = 172) or chemotherapy (pemetrexed 500 mg/m 2 plus cisplatin 75 mg/m 2 or carboplatin at area under the curve 5 to 6, every 3 weeks for ≤ six cycles; n = 171). Patients with stable treated brain metastases (tBM) were eligible. Intracranial efficacy was assessed at baseline and every 6 or 12 weeks in patients with or without known brain metastases (BM), respectively; intracranial time to tumor progression (IC-TTP; per protocol) and intracranial disease control rate (IC-DCR; post hoc) were measured. The intent-to-treat population was also assessed. Results Of 343 patients in the intent-to-treat population, 23% had tBM at baseline. A nonsignificant IC-TTP improvement was observed with crizotinib in the intent-to-treat population (hazard ratio [HR], 0.60; P = .069), patients with tBM (HR, 0.45; P = .063), and patients without BM (HR, 0.69; P = .323). Among patients with tBM, IC-DCR was significantly higher with crizotinib versus chemotherapy at 12 weeks (85% v 45%, respectively; P &lt; .001) and 24 weeks (56% v 25%, respectively; P = .006). Progression-free survival was significantly longer with crizotinib versus chemotherapy in both subgroups (tBM present: HR, 0.40; P &lt; .001; median, 9.0 v 4.0 months, respectively; BM absent: HR, 0.51; P &lt; .001; median, 11.1 v 7.2 months, respectively) and in the intent-to-treat population (HR, 0.45; P &lt; .001; median, 10.9 v 7.0 months, respectively). Conclusion Compared with chemotherapy, crizotinib demonstrated a significantly higher IC-DCR in patients with tBM. Improvements in IC-TTP were not statistically significant in patients with or without tBM, although sensitivity to detect treatment differences in or between the two subgroups was low.
Abstract 4412: Prognostic significance of NF-κB in Middle Eastern diffuse large B cell lymphoma and efficacy of NF-κB inhibition as a viable therapeutic target
Authors: Prashant Bavi, Shahab Uddin, Rong Bu, Maqbool Ahmed, Jehad Abubaker, Fouad Al-Dayel, Valorie Balde, Padmanabhan Naidu, Hassan Al-Dossari, Zeeshan Qadri, Sarita E. Prabhakaran, Azhar R. Hussain, Khawla S. Al-Kuraya
Journal: Cancer Research (2011)

Abstract NF-kB is frequently over expressed in variety of NHL and has been implicated in lymphomagenesis; however, its role in diffuse large B-cell lymphoma (DLBCL) as a prognostic biomarker has not been fully elucidated. Therefore, we investigated the role of NF-kB and its association with clinico-pathological features in a tissue microarray cohort of 230 DLBCL patient samples. We then elucidated the role of NF-kB inhibition on cell viability and apoptosis in-vitro using DLBCL cell lines. Using immunohistochemistry, NF-kB was detected in 25.6% (52/203) DLBCL tumors, was associated with activated B cell (ABC) phenotype (p=0.0054) and overexpression of anti apoptotic marker, XIAP (p=0.0013). DLBCL with nuclear expression of NF-kB showed a significantly poor overall survival as compared to those with no NF-kB expression (p=0.0236). In the multivariate analysis using Cox Proportional Hazard model for IPI and NF-kB expression, the relative risk was 2.97 for high NF-kB expression (95% CI 1.27-6.94; p=0.0113) and 7.55 for high IPI group (95% CI 3.34-18.35; p&amp;lt;0.0001). In-vitro, Bay11-7085 inhibited constitutively active NF-kB expression in a dose dependent manner. Inhibition of NF-kB also down-regulated expression of down-stream target gene products, such as Bcl-2, Bcl-Xl, XIAP and Survivin leading to apoptosis via the mitochondrial apoptotic pathway. NF-kB overexpression was found to be an independent prognostic marker for poor survival in DLBCL. Inhibition of NF-kB caused apoptosis via activation of the mitochondrial apoptotic pathway. Altogether, these results suggest that NF-kB may be a useful prognostic biomarker and a potential target for therapeutic intervention in DLBCL. 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 4412. doi:10.1158/1538-7445.AM2011-4412
The Runx-PU.1 pathway preserves normal and AML/ETO9a leukemic stem cells
Authors: Philipp B. Staber, Pu Zhang, Min Ye, Robert S. Welner, Elena Levantini, Annalisa Di Ruscio, Alexander K. Ebralidze, Christian Bach, Hong Zhang, Junyan Zhang, Katrina Vanura, Ruud Delwel, Henry Yang, Gang Huang, Daniel G. Tenen
Journal: Blood (2014)
Epidural Lipomatosis Causing Spinal Cord Compression
Authors: Moahad Saeed Dar, Shadi Daoud
Journal: New England Journal of Medicine (2003)

Cleveland Clinic Foundation Cleveland, OH 44195 68-year-old woman with corticosteroid-dependent chronic obstructive pulmonary disease was admitted to the hospital for worsening respiratory symptoms and for new-onset weakness in both legs. Physical examination revealed poor air entry and rales throughout both lung fields, as well as decreased sensation to a pinprick in the right leg, no sensation in the left leg, and paralysis of both legs. A T 1 -weighted sagittal magnetic resonance imaging (MRI) scan of the spine (Panel A) revealed multiple compression fractures of the thoracic and lumbar vertebrae (arrowheads) and spinal epidural lipomatosis (arrows). A T 1 -weighted axial MRI scan (Panel B) confirmed the presence of spinal cord compression (arrowhead) secondary to epidural lipomatosis (arrows). The lipomatosis was most pronounced from T4 to T10 (Panel C). Neurosurgical correction of the cord compression was considered, but the patient’s severe chronic obstructive pulmonary disease precluded surgery. The patient died shortly thereafter. Spinal epidural lipomatosis can develop spontaneously or as a result of Cushing’s disease or long-term corticosteroid use. Localization to and compression of the spinal cord at the thoracic level are typical of this disease. MRI is the diagnostic procedure of choice. The usual treatment is immediate laminectomy with the removal of epidural fat and a decrease in the corticosteroid dose.
Plasma-Cell Dyscrasia with Polyneuropathy
Authors: G. Diego Miralles, Judith R. O'Fallon, Nicholas J. Talley
Journal: New England Journal of Medicine (1992)

The POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome and osteosclerotic myeloma (polyneuropathy and sclerotic bone lesions) may both be manifestations of plasma-cell dyscrasia, but the interrelation of these diseases is not clear. We therefore set out to define the clinical spectrum of disease in patients with plasma-cell dyscrasia and polyneuropathy who have the complete or incomplete form of the POEMS syndrome or osteosclerotic myeloma.
AB1239 The detection of erosions in patients with rheumatoid arthritis by computer-aided joint space analysis
Authors: A. Pfeil, J. Boettcher, G. Lehmann, A. Hansch, P. Oelzner, G. Wolf
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objectives</h3> The aim of this study was to asses the Z-Score of computer-aided joint space analysis (CAJSA) as a novel approach for the quantification of finger joint space narrowing and its potential to quantify erosive disease in patients with rheumatoid arthritis (RA). <h3>Methods</h3> 186 patients (133 female and 53 male) with a verified RAunderwent computerized semi-automated measurements of finger joint space width by the CAJSA-technique (Radiogrammetry Kit, Version 1.3.6) based radiographs. The Z-Score as an age and gender independent parameter of joint space narrowing was calculated and compared to the Sharp-van der Heijde (SHS) Score. <h3>Results</h3> The Z-Scores of finger articulations in patients with RA were generally decreased. MCP-articulations showed a continuous significant decline of -1.65±0.30 SD dependent on SHS. The PIP-joints also revealed a significant reduction of the Z-Score (-0.96±0.31 SD). Additionally, the potential of the technique for detection of erosions was performed and presented a sensitivity and specificity of the Z-Score for JSD-MCP with 85.4% and 55.2%. <h3>Conclusions</h3> The Z-Score shows the potential as a surrogate marker of RA progression which comprehends the early identification of patients with RA and inparticular those with erosive course of the disease, enabling a timely therapeutic strategy for cartilage protection. <h3>Disclosure of Interest</h3> None Declared
A8.11 gilz-dependent activin a production by MSC inhibits TH17 differentiation
Authors: P Luz-Crawford, G Tejedor, N Ipseiz, J Pène, E Morand, E Beaulieu, C Jorgensen, D Noël, F Djouad
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background and Objectives</h3> Together with B cells, Th1 and Th17 cells are the immune cell subsets mainly associated with the development of autoimmune diseases. Mesenchymal stem cells (MSC) display immunosuppressive properties via the inhibition of T cell activation and proliferation. Recent evidences have shown that MSC negatively regulate both Th1 and Th17 responses and restore the balance between T-helper and T regulatory cells. However, the molecular mechanisms by which mouse MSC exert their immunosuppressive effect on Th1 and Th17 cells have not been fully elucidated. We investigated the role of Gilz, an anti-inflammatory protein expressed by MSC. <h3>Material and Methods</h3> We used MSC isolated from the bone marrow of wild-type (WT MSC) or Gilz-deficient (Gilz<sup>-/-</sup>MSC) mice. T cells obtained from the spleen of WT mice were differentiated into Th1 or Th17 cells. After 6 days of T cell/MSC coculture, proliferation was quantified and the number of IFN-γ- and IL-17-producing Th1 and Th17 cells, respectively, was measured by flow cytometry. Using ELISA, we quantified the production of Activin A, PGE<sub>2</sub> and NO<sub>2</sub> in the supernatants of differentiated Th1 or Th17 cells in the presence or absence of MSC. Phosphorylation of Smad-2/-3 in CD4<sup>+</sup> T cells induced to differentiate into Th17 cells was determined using an ELISA-based assay using fluorogenic substrates kit. <h3>Results</h3> In the coculture assay, the presence of Gilz<sup>-/-</sup> MSC decreased the proliferation rate of CD4<sup>+</sup> T cell differentiating into Th1 or Th17, although to a lesser extent compared to WT MSC. Moreover, while WT MSC significantly decrease the percentage of CD4<sup>+</sup>T cells undergoing Th1 and Th17 polarization, Gilz<sup>-/-</sup> MSC displayed a reduced suppressive effect on CD4<sup>+</sup> T cell differentiation. The impaired immunomodulatory functions of Gilz<sup>-/-</sup> MSC were accompanied by their reduced capacity to produce NO<sub>2</sub> and Activin A as compared to WT MSC. Finally, we showed that under Th17 skewing conditions, the release of Activin A by WT MSC repressed the Th17 differentiation program through Smad3/2 activation and promoted the generation of IL-10 producing CD4<sup>+</sup> T cells. <h3>Conclusion</h3> Our data indicate that Gilz-dependent production of Activin A participates in the inhibition of Th17 cell development by MSC<i>. Thereby, via Gilz expression, MSC offer</i> a potential mean of impacting on autoimmune diseases mediated by Th17 cells.
PWE-193 Changes in taste Preference after Colorectal Surgery
Authors: P Hiotis, S Welchman, S Lewis
Journal: Gut (2013)

<h3>Introduction</h3> Early postoperative nutrition is of clinical benefit. However, patients are often initially reluctant to eat after surgery. Dysguesia and alterations in food preference are often reported. We conducted a study to describe perioperative changes in taste and food preference with a view to being able to optimise food choices and thus improve intake. <h3>Methods</h3> Patients undergoing colorectal surgery were recruited. Three sets of tests were conducted, pre-operatively and on post-operative days (POD) 1, 2 &amp; 3. In Test 1, patients were asked to rate the palatability (Horrible-Nice, using Likert scales (0–100%)) of a nutritional supplement flavoured with ‘standard’ concentrations of the 6 core tastes (sweet, sour, salt, bitter, spicy &amp; savoury). In Test 2, patients were shown photos of foods representative of the core tastes and asked to rate them in terms of appeal. Test 3, snack box containing representative foods of the core tastes were rated by patients. Differences from baseline were assessed using t-tests. <h3>Results</h3> 31 patients completed the study, M:F = 21:10, median age of 72 (33–82). Test 1, enhanced taste from baseline was seen on POD1 (p &lt; 0.01) for salty, sweat &amp; spicy taste figure 1. Test 2, only salty food (popcorn) scored higher (p &lt; 0.01) than baseline (figure 2) all other foods scored lower. Foods representing bitter and sour exhibited the greatest decline (40.4% for gherkins, 38.7% for grapefruit). Test 3, patients rated sweat (fudge) 63%, salty (crackers) 50% best at POD 1 (p &lt; 0.01) and sour (gherkins) 22%, spicy (Bombay mix) 16% worst. With all 3 Tests, scores reverted to baseline by POD 3. <h3>Conclusion</h3> After surgery patients rated sweat and salty snack foods greatest. This was confirmed by tests of palatability and appeal. Though while spicy and savoury palability tests scored highly patients did not find the snakes particularly desirable. Further work is required to explore patients food preferences post surgery. <h3>Disclosure of Interest</h3> None Declared.
536Small-size platelet microparticles trigger platelet and monocyte functionality and modulate thrombogenesis via P-selectin
Authors: S Montoro-Garcia, E Shantsila, D Hernandez-Romero, E Jover, M Valdes, F Marin, GYH Lip
Journal: Cardiovascular Research (2014)

Purpose: To characterise morphological and phenotypical differences between small-size platelet MPs (sPMP) released from resting platelets, thrombin activation and platelet disruption (termed as platelet debris [PD]) using our novel technological approach. Besides, we aimed to assess their prothrombotic properties by evaluating the ability to induce thrombus formation, platelet and monocyte activation ex vivo.
Abstract LB-50: Street smarts: cancer education and outreach in the homeless community
Authors: Cynthia Ryan
Journal: Cancer Research (2012)

Abstract In response to a year-long investigation of cancer among the homeless in Birmingham, AL, this presenter created an education program called “Street Smarts.” Findings from a focus group consisting of homeless women diagnosed with stage IV breast cancer revealed competing values (poor self-esteem and body image, limited health care resources, etc.) preventing individuals in this population from seeking diagnosis or treatment for cancer, even when free-of-charge options are available. Street Smarts brings together members of this underserved community for a day of pampering while educating them about breast cancer screening and health care alternatives. The program is funded in partnership with the North Central Alabama Susan G. Komen Foundation. 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 LB-50. doi:1538-7445.AM2012-LB-50