tbuckley/cabot-search huggingface dataset:
Bullous pemphigoid associated with chronic B-cell lymphatic leukaemia: the anti-230-kDa autoantibody is not synthesized by leukaemic cells
Authors: None Misery, None Cambazard, None Rimokh, None Ghohestani, None Magaud, None Gaudillere, None Perrot, None Berard, None Claudy, None Guyotat, None Schmitt, None Vincent
Journal: British Journal of Dermatology (1999)
Dipeptidyl Peptidase Inhibits Malignant Phenotype of Prostate Cancer Cells by Blocking Basic Fibroblast Growth Factor Signaling Pathway
Authors: Umadevi V. Wesley, Michelle McGroarty, Asal Homoyouni
Journal: Cancer Research (2005)

Abstract Dipeptidyl peptidase IV (DPPIV) is a serine protease with tumor suppressor function. It regulates the activities of mitogenic peptides implied in cancer development. Progression of benign prostate cancer to malignant metastasis is linked to increased production of basic fibroblast growth factor (bFGF), a powerful mitogen. In this study, using in vitro model system we show that DPPIV loss is associated with increased bFGF production in metastatic prostate cancer cells. DPPIV reexpression in prostate cancer cells blocks nuclear localization of bFGF, reduces bFGF levels, inhibits mitogen-activated protein kinase (MAPK)-extracellular signal-regulated kinase (ERK)1/2 activation, and decreases levels of urokinase-type plasminogen activator, known downstream effectors of bFGF signaling pathway. These molecular changes were accompanied by induction of apoptosis, cell cycle arrest, inhibition of in vitro cell migration, and invasion. Silencing of DPPIV by small interfering RNA resulted in increased bFGF levels and restoration of mitogen-activated protein kinase (MAPK)-extracellular signal-regulated kinase (ERK)1/2 activation. These results indicate that DPPIV inhibits the malignant phenotype of prostate cancer cells by blocking bFGF signaling pathway.
Phase III Study of the Value of Thalidomide Added to Melphalan Plus Prednisone in Elderly Patients With Newly Diagnosed Multiple Myeloma: The HOVON 49 Study
Authors: Pierre Wijermans, Martijn Schaafsma, Fabian Termorshuizen, Rianne Ammerlaan, Shulamiet Wittebol, Harm Sinnige, Sonja Zweegman, Marinus van Marwijk Kooy, René van der Griend, Henk Lokhorst, Pieter Sonneveld
Journal: Journal of Clinical Oncology (2010)

For several decades, the treatment of elderly patients with multiple myeloma (MM) has consisted of melphalan and prednisone (MP). The Dutch-Belgium Hemato-Oncology Cooperative Group (HOVON) investigated the efficacy of thalidomide added to MP (MP-T) in a randomized phase III trial. The objective of this study was to investigate the efficacy, toxicity, and effects on quality of life of MP-T.A randomized phase III trial compared standard MP with MP-T (thalidomide 200 mg/d) in newly diagnosed patients with multiple myeloma older than age 65 years. Maintenance therapy with thalidomide 50 mg/d was administered to patients after MP-T until relapse. The primary end point was event-free survival (EFS); response rate, overall survival (OS), and progression-free survival (PFS) were secondary end points.An intent-to-treat analysis of 333 evaluable patients showed significantly higher response rates in MP-T-treated patients compared with MP-treated patients a response (> or = partial response: 66% v 45%, respectively; P < .001; and > or = very good partial response [VGPR]: 27% v 10%, respectively; P < .001). EFS was 13 months with MP-T versus 9 months with MP (P < .001). OS was 40 months with MP-T versus 31 months with MP (P = .05).This study demonstrates that thalidomide improves the response rate and VGPR in elderly patients with newly diagnosed MM. MP-T also results in a better EFS, PFS, and OS.
Targeting Angiogenesis via a c-Myc/Hypoxia-Inducible Factor-1α–Dependent Pathway in Multiple Myeloma
Authors: Jing Zhang, Martin Sattler, Giovanni Tonon, Clemens Grabher, Samir Lababidi, Alexander Zimmerhackl, Marc S. Raab, Sonia Vallet, Yiming Zhou, Marie-Astrid Cartron, Teru Hideshima, Yu-Tzu Tai, Dharminder Chauhan, Kenneth C. Anderson, Klaus Podar
Journal: Cancer Research (2009)

Bone marrow angiogenesis is associated with multiple myeloma (MM) progression. Here, we report high constitutive hypoxia-inducible factor-1alpha (Hif-1alpha) expression in MM cells, which is associated with oncogenic c-Myc. A drug screen for anti-MM agents that decrease Hif-1alpha and c-Myc levels identified a variety of compounds, including bortezomib, lenalidomide, enzastaurin, and adaphostin. Functionally, based on transient knockdowns and overexpression, our data delineate a c-Myc/Hif-1alpha-dependent pathway mediating vascular endothelial growth factor production and secretion. The antiangiogenic activity of our tool compound, adaphostin, was subsequently shown in a zebrafish model and translated into a preclinical in vitro and in vivo model of MM in the bone marrow milieu. Our data, therefore, identify Hif-1alpha as a novel molecular target in MM and add another facet to anti-MM drug activity.
The Angiocardiographic Diagnosis of Left Atrial Thrombosis
Authors: LOUIS A. SOLOFF, JACOB ZATUCHNI
Journal: Circulation (1956)

With the advent of modern cardiac surgery the clinical diagnosis of intramural thrombi, ball valve thrombi and myxomatous and other tumors in the left atrium has assumed great importance. It is shown here that a diagnosis of thrombosis within the left atrium is possible by angiocardiography. The angiocardiographic features of mural and ball valve thrombi of the left atrium and of left auricular thrombosis are described.
Feeding, Simvastatin, and Linezolid
Authors: Biren B. Kamdar, Jason A. Akulian, Andrew T. Braun
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Nutritional support is important but particularly challenging for patients receiving mechanical ventilation.Current guidelines for this population recommend early initiation of enteral feeding, supported by data associating enteral feeding with improved mortality and infection outcomes (2).Despite these recommendations, the optimal dose of enteral nutrition in intensive care unit patients remains unknown.Although some studies suggest that full enteric nutrition improves outcomes, others have demonstrated that trophic (minimal) feedings are sufficient and produce fewer gastrointestinal complications (2).To resolve these conflicting data, Rice and colleagues present the results of an ARDS Clinical Trials Network randomized controlled trial comparing full versus trophic feeding in critically ill patients with acute lung injury (ALI) (1).Within 48 hours of ALI onset and 72 hours of initiation of mechanical ventilation, patients at 44 hospitals were randomized to receive 6 days of either a full-feeding protocol, starting at 25 ml/hour and up-titrated as tolerated toward a caloric goal, or a 10-ml/hour trophicfeeding protocol.After 6 days, patients still receiving mechanical ventilation were given the full-feeding protocol.During the study period, the 492 patients in the full-feeding group received approximately 1,300 kcal each day (80% of goal), whereas the 508 patients in the trophic-feeding group received approximately 400 kcal (25% of goal).Comparing the full-and trophic-feeding groups, there were no significant differences in ventilator-free days (15.0 vs. 14.9;P ¼ 0.89), 60-day mortality (22.2 vs. 23.2%;P ¼ 0.77), infection rates, organ failure-free days, or intensive care unit-free days.The trophic-feeding group had significantly lower gastric residual volumes and rates of regurgitation, emesis, and constipation, but actual rates of these complications were low in both groups.The strengths of this study include its randomized, intentionto-treat design, large size, and use of standardized dosing protocols.Limitations include its open-label, nonequivalence design and the exclusion of critically ill patients without ALI.Overall, this well-designed randomized controlled trial demonstrated no difference in ventilator-free days or mortality with initial full versus trophic feeding, and supports the relative safety of both strategies in ALI.It remains unknown whether other clinically important outcomes related to the timing or duration of feeding exist to favor one strategy over the other.
An optimized microarray platform for assaying genomic variation in Plasmodium falciparum field populations
Authors: John C Tan, Becky A Miller, Asako Tan, Jigar J Patel, Ian H Cheeseman, Tim JC Anderson, Magnus Manske, Gareth Maslen, Dominic P Kwiatkowski, Michael T Ferdig
Journal: Genome biology (2011)

Abstract We present an optimized probe design for copy number variation (CNV) and SNP genotyping in the Plasmodium falciparum genome. We demonstrate that variable length and isothermal probes are superior to static length probes. We show that sample preparation and hybridization conditions mitigate the effects of host DNA contamination in field samples. The microarray and workflow presented can be used to identify CNVs and SNPs with 95% accuracy in a single hybridization, in field samples containing up to 92% human DNA contamination.
Chemotherapy Sensitivity and Response Assays: Are the ASCO Guidelines for Clinical Trial Design Too Restrictive?
Authors: H. Samuel Wieand
Journal: Journal of Clinical Oncology (2005)

chemosensitivity testing" at the time this approach first received broad attention.First, the assay methodologies themselves were not rigorously validated for broad use, and second, only a handful of modestly active chemotherapeutics were available.It is no surprise, then, to find that although early randomized trials that tested the hypothesis that assay selected therapy would be better than "physician's choice" resulted in higher response rates, no significant improvements in overall survival were found.Enabling advances over the past 30 years in both the technology of in vitro tumor culture methods and in the diversity and safety of agents used to treat cancer led to Medicare coverage for in vitro drug resistance assays.Is it appropriate to conclude that these assays don't work, or should we consider that flaws in their early implementation obscured their appropriate application to detect drug resistance?In other words, should we throw the baby out with the bathwater?While it is clear that in vitro drug resistance assays can assist physicians in the elimination of ineffective drugs, it may be time to revisit the question "can assay directed therapy prolong patient survival?"Partially on the basis of the recent article by Loizzi et al 17 demonstrating a significant survival advantage for ovarian cancer patients who were treated with assay assisted therapy, the Gynecological Oncology Group has approved the concept of performing a trial to assess assay directed therapy for patients with platinum resistant epithelial ovarian carcinoma.We await the results of this and other "assay directed" trials with the hope that the time for successful tailored therapeutics has finally come.
Acid sphingomyelinase, a novel pathway for pulmonary vasoconstriction. Activation by apoptotic T cell microparticles and Fas ligand
Authors: Javier Javier Moral-Sanz, Daniel Morales-Cano, Bianca Barreira, Raffaella Soleti, Laura Moreno, Angel Cogolludo, Ramaroson Andriantsitohaina, Carmen Martinez, Francisco Perez-Vizcaino
Journal: European Respiratory Journal (2014)

Microparticles (MPs) are small membrane vesicles released from stimulated and/or apoptotic cells. We hypothesized that MPs have acute effects on pulmonary vascular contractility and Kv channel function. MPs were isolated from T lymphocytes treated with actinomycin D. Small pulmonary arteries (PA) from male Wistar rats were mounted for contractile tension recording in a wire myograph. Potassium currents were recorded in PA smooth muscle cells (PASMC) using the patch clamp technique. MPs (10 mg protein/ml) reduced Kv current amplitude, depolarized PASMC and induced a slow developing sustained contraction in PA that was blunted by the L-type Ca 2+  channel blocker nifedipine. MP-induced contraction was attenuated by the anticeramide antibody and by the acid sphingomyelinase (aSMase) inhibitor D-609, but not by the neutral sphingomyelinase (nSMase) inhibitor GW4869. Similar to MPs, FasL-induced contraction was attenuated by the anticeramide antibody and by D-609 but not by GW4869. MPs also increased reactive oxygen species (ROS) in human PASMC in culture and the contractile effect in PA was abolished by the ROS scavenger tiron. In conclusion, MPs from apoptotic T lymphocytes produce pulmonary vasoconstriction involving the activation of Fas, acid sphingomyelinase, increase in ROS and inhibition of Kv channels.
Prospective Randomized Trial Comparing Mitomycin, Cisplatin, and Protracted Venous-Infusion Fluorouracil (PVI 5-FU) With Epirubicin, Cisplatin, and PVI 5-FU in Advanced Esophagogastric Cancer
Authors: P. Ross, M. Nicolson, D. Cunningham, J. Valle, M. Seymour, P. Harper, T. Price, H. Anderson, T. Iveson, T. Hickish, F. Lofts, A. Norman
Journal: Journal of Clinical Oncology (2002)

PURPOSE: We report the results of a prospectively randomized study that compared the combination of epirubicin, cisplatin, and protracted venous-infusion fluorouracil (PVI 5-FU) (ECF) with the combination of mitomycin, cisplatin, and PVI 5-FU (MCF) in previously untreated patients with advanced esophagogastric cancer. PATIENTS AND METHODS: Five hundred eighty patients with adenocarcinoma, squamous carcinoma, or undifferentiated carcinoma were randomized to receive either ECF (epirubicin 50 mg/m 2 every 3 weeks, cisplatin 60 mg/m 2 every 3 weeks and PVI 5-FU 200 mg/m 2 /d) or MCF (mitomycin 7 mg/m 2 every 6 weeks, cisplatin 60 mg/m 2 every 3 weeks, and PVI 5-FU 300 mg/m 2 /d) and analyzed for survival, response, toxicity, and quality of life (QOL). RESULTS: The overall response rate was 42.4% (95% confidence interval [CI], 37% to 48%) with ECF and 44.1% (95% CI, 38% to 50%) with MCF (P = .692). Toxicity was tolerable, and there were only two toxic deaths. ECF resulted in more grade 3/4 neutropenia and grade 2 alopecia, but MCF caused more thrombocytopenia and plantar-palmar erythema. Median survival was 9.4 months with ECF and 8.7 months with MCF (P = .315); at 1 year, 40.2% (95% CI, 34% to 46%) of ECF and 32.7% (95% CI, 27% to 38%) of MCF patients were alive. Median failure-free survival was 7 months with both regimens. Global QOL scores were better with ECF at 3 and 6 months. CONCLUSION: This study confirms response, survival, and QOL benefits of ECF observed in a previous randomized study. The equivalent efficacy of MCF was demonstrated, but QOL was superior with ECF. ECF remains one of the reference treatments for advanced esophagogastric cancer.
Involvement of the autonomic nervous system in the in vivo memory to glucose of pancreatic beta cell in rats.
Authors: J M N'Guyen, C Magnan, M C Laury, C Thibault, J Leveteau, M Gilbert, L Pénicaud, A Ktorza
Journal: Journal of Clinical Investigation (1994)

The fact that the potentiating effect of prolonged hyperglycemia on the subsequent insulin secretion is observed in vivo but not in vitro suggests the involvement of extrapancreatic factors in the in vivo memory of pancreatic beta cells to glucose. We have investigated the possible role of the autonomic nervous system. Rats were made hyperglycemic by a 48-h infusion with glucose (HG rats). At the end of glucose infusion as well as 6 h postinfusion, both parasympathetic and sympathetic nerve activities were profoundly altered: parasympathetic and sympathetic activities, assessed by the firing rate either of the thoracic vagus nerve or the superior cervical ganglion, were dramatically increased and decreased, respectively. Moreover, 6 h after the end of glucose infusion, insulin secretion in response to a glucose load was dramatically increased in HG rats compared to controls. To determine whether these changes could be responsible for the increased sensitivity of the beta cell to glucose, insulin release in response to glucose was measured in HG and control rats, either under subdiaphragmatic vagotomy or after administration of the alpha 2A-adrenergic agonist oxymetazoline. Both treatments partially abolished the hyperresponsiveness of the beta cell to glucose in HG rats. Therefore chronic hyperglycemia brings about changes in the activity of the autonomic nervous system, which in turn are responsible, at least in part, for the generation of enhanced beta cell responsiveness to glucose in vivo.
Acetylcholine and Molecular Components of its Synthesis and Release Machinery in the Urothelium
Authors: Katrin S. Lips, Julia Wunsch, Shirin Zarghooni, Thomas Bschleipfer, Konstantin Schukowski, Wolfgang Weidner, Ignaz Wessler, Ulrich Schwantes, Hermann Koepsell, Wolfgang Kummer
Journal: European Urology (2006)
Differential Radiation Protection of Salivary Glands versus Tumor by Tempol with Accompanying Tissue Assessment of Tempol by Magnetic Resonance Imaging
Authors: Ana P. Cotrim, Fuminori Hyodo, Ken-Ichiro Matsumoto, Anastasia L. Sowers, John A. Cook, Bruce J. Baum, Murali C. Krishna, James B. Mitchell
Journal: Clinical Cancer Research (2007)

The nitroxide free radical, Tempol, was evaluated for potential differential radiation protection of salivary glands and tumor using fractionated radiation. Mechanistic information was explored by monitoring the presence and bioreduction of Tempol in both tissues noninvasively by magnetic resonance imaging (MRI).Female C3H mice were immobilized using custom-made Lucite jigs for localized irradiation (five daily fractions) either to the oral cavity or tumor-bearing leg. Tempol (275 mg/kg) was administered (i.p.) 10 min before each radiation fraction. Salivary gland damage was assessed 8 weeks after radiation by measuring pilocarpine-mediated saliva output. Tumor growth was assessed by standard radiation regrowth methods. Dynamic T1-weighted magnetic resonance scans were acquired before and after Tempol injection using a 4.7T animal MRI instrument.Tempol treatment was found to protect salivary glands significantly against radiation damage (approximately 60% improvement); whereas no tumor protection was observed. Intracellular reduction of Tempol to the nonradioprotective hydroxylamine as assessed by MRI was 2-fold faster in tumor compared with salivary glands or muscle.Tempol provided salivary gland radioprotection and did not protect tumor, consistent with the hypothesis that differential radioprotection by Tempol resides in faster reduction to the nonradioprotective hydroxylamine in tumor compared with normal tissues. The unique paramagnetic properties of Tempol afforded noninvasive MRI monitoring of dynamic changes of Tempol levels in tissue to support the finding. These data support further development and consideration of Tempol for human clinical trials as a selective protector against radiation-induced salivary gland damage.
Clinical Needs Assessment of Middle and High School Students Following the 1995 Oklahoma City Bombing
Authors: Betty Pfefferbaum, Sara Jo Nixon, Ronald S. Krug, Rick D. Tivis, Vern L. Moore, Janice M. Brown, Robert S. Pynoos, David Foy, Robin H. Gurwitch
Journal: American Journal of Psychiatry (1999)

This clinical assessment was designed to identify middle and high school students in need of formal evaluation for posttraumatic response symptoms following the 1995 bombing of the Alfred P. Murrah Federal Building in Oklahoma City.A clinical needs assessment instrument was developed and administered to grade 6 through 12 students 7 weeks after the bombing (N = 3,218).More than 40% of the students reported knowing someone injured, and more than one-third reported knowing someone killed in the blast. Posttraumatic stress symptoms at 7 weeks significantly correlated with gender, exposure through knowing someone injured or killed, and bomb-related television viewing.This study documents the intensity of community exposure to the bombing and the lingering symptoms of stress. The assessment was used in planning for clinical service delivery, training professional responders, and supporting funding requests.
Low-Dose Aspirin Use and Performance of Immunochemical Fecal Occult Blood Tests
Authors: Hermann Brenner, Sha Tao, Ulrike Haug
Journal: JAMA (2010)

Immunochemical fecal occult blood tests (iFOBTs) are potentially promising tools for colorectal cancer screening. Low-dose aspirin use, which increases the likelihood of gastrointestinal bleeding, is common in the target population for colorectal cancer screening.To assess the association of low-dose aspirin use with the performance of 2 quantitative iFOBTs in a large sample of patients undergoing colorectal cancer screening.Diagnostic study conducted from 2005 through 2009 at internal medicine and gastroenterology practices in southern Germany including 1979 patients (mean age, 62.1 years): 233 regular users of low-dose aspirin (167 men, 67 women) and 1746 who never used low-dose aspirin (809 men, 937 women).Sensitivity, specificity, positive and negative predictive values, and area under receiver operating characteristic (ROC) curves in detecting advanced colorectal neoplasms (colorectal cancer or advanced adenoma) with 2 quantitative iFOBTs.Advanced neoplasms were found in 24 users (10.3%) and 181 nonusers (10.4%) of low-dose aspirin. At the cut point recommended by the manufacturer, sensitivities of the 2 tests were 70.8% (95% confidence interval [CI], 48.9%-87.4%) for users compared with 35.9% (95% CI, 28.9%-43.4%) for nonusers and 58.3% (95% CI, 36.6%-77.9%) for users compared with 32.0% (95% CI, 25.3%-39.4%) for nonusers (P = .001 and P = .01, respectively). Specificities were 85.7% (95% CI, 80.2%-90.1%) for users compared with 89.2% (95% CI, 87.6%-90.7%) for nonusers and 85.7% (95% CI, 80.2%-90.1%) for users compared with 91.1% (95% CI, 89.5%-92.4%) for nonusers (P = .13 and P = .01, respectively). The areas under the ROC curve were 0.79 (95% CI, 0.68-0.90) for users compared with 0.67 (95% CI, 0.62-0.71) for nonusers and 0.73 (95% CI, 0.62-0.85) for users compared with 0.65 (95% CI, 0.61-0.69) for nonusers (P = .05 and P = .17, respectively). Among men, who composed the majority of low-dose aspirin users, the areas under the ROC curve were 0.87 (95% CI, 0.76-0.98) for users compared with 0.68 (95% CI, 0.63-0.74) for nonusers and 0.81 (95% CI, 0.68-0.93) for users compared with 0.67 (95% CI, 0.61-0.72) for nonusers (P = .003 and P = .04, respectively).For 2 iFOBTs, use of low-dose aspirin compared with no aspirin was associated with a markedly higher sensitivity for detecting advanced colorectal neoplasms, with only a slightly lower specificity.
A phase 3 randomized, double-blind, placebo-controlled trial of ganitumab or placebo in combination with gemcitabine as first-line therapy for metastatic adenocarcinoma of the pancreas: the GAMMA trial
Authors: C.S. Fuchs, S. Azevedo, T. Okusaka, J.-L. Van Laethem, L.R. Lipton, H. Riess, C. Szczylik, M.J. Moore, M. Peeters, G. Bodoky, M. Ikeda, B. Melichar, R. Nemecek, S. Ohkawa, A. Świeboda-Sadlej, S.A. Tjulandin, E. Van Cutsem, R. Loberg, V. Haddad, J.L. Gansert, B.A. Bach, A. Carrato
Journal: Annals of Oncology (2015)