tbuckley/cabot-search huggingface dataset:
Immunoglobulin E induces VEGF production in mast cells and potentiates their pro-tumorigenic actions through a Fyn kinase-dependent mechanism
Authors: Guillermina Yanek Jiménez-Andrade, Alfredo Ibarra-Sánchez, Diana González, Mónica Lamas, Claudia González-Espinosa
Journal: Journal of Hematology & Oncology (2013)

Abstract Background High concentrations of plasmatic IgE have been related to distinct systemic inflammatory conditions that frequently predispose individuals to hypersensitivity reactions. Although effects of IgE have been suggested to relay on the low-intensity activation of distinct effector elements of the immune system, such as mast cells (MC), experimental evidence on the role of IgE-induced production of inflammatory mediators on specific pathologies is scarce. MC are an important component in tumor microenvironment where they seem to secrete a number of immunomodulatory and angiogenic mediators, such as the Vascular Endothelial Growth Factor (VEGF) by not well-described mechanisms. In this work, we investigated the effect of monomeric IgE (in the absence of antigen) on the production of VEGF in MC, analyzed if monomeric IgE could exacerbate the pro-tumorigenic properties of that cell type and characterized some of the molecular mechanisms behind the effects of IgE on VEGF production and tumor growth. Methods For in vitro studies, murine bone marrow-derived mast cells (BMMCs) were used. Pharmacological inhibitors and phosphorylation of key elements controlling VEGF secretion and protein translation were used to characterize the mechanism of VEGF production triggered by IgE. In vivo , the effect of a single i.v. administration of monomeric IgE on B16 melanoma tumor weight, intratumoral blood vessel formation and tumor-associated MC was assessed in four groups of mice: MC-proficient (WT), MC-deficient (Wsh), Wsh reconstituted with MC derived from WT mice (Wsh Rec WT) and Wsh reconstituted with MC derived from Fyn −/− mice (Wsh Rec Fyn −/−). Results Monomeric IgE induced VEGF secretion through a Fyn kinase-dependent mechanism and modulated de novo protein synthesis modifying the activity of the translational regulator 4E-BP1 in BMMCs. In vivo , monomeric IgE increased melanoma tumor growth, peritumoral MC and blood vessel numbers in WT but not in Wsh mice. The positive effects of IgE on melanoma tumor growth were reproduced after reconstitution of Wsh mice with WT but not with Fyn −/− BMMCs. Conclusion Our data suggest that monomeric IgE, in the absence of antigen, induces VEGF production in MC and in vivo contributes to melanoma tumor growth through a Fyn kinase-dependent mechanism.
Bariatric Surgery for Morbid Obesity
Authors: Eric J. DeMaria
Journal: New England Journal of Medicine (2007)

A 44-year-old morbidly obese woman inquires about bariatric surgery, a treatment option for patients with a body-mass index of 40 or more (or of 35 or more when there are coexisting medical conditions). Bariatric surgery has been shown to result in substantial weight loss and resolution of associated conditions. A successful clinical outcome requires an experienced multidisciplinary management team and an informed patient who will follow a plan of long-term management and self-care.
A case of meningoencephalitis by the relapsing fever spirochaete Borrelia miyamotoi in Europe
Authors: Joppe W R Hovius, Bob de Wever, Maaike Sohne, Matthijs C Brouwer, Jeroen Coumou, Alex Wagemakers, Anneke Oei, Henrike Knol, Sukanya Narasimhan, Caspar J Hodiamont, Setareh Jahfari, Steven T Pals, Hugo M Horlings, Erol Fikrig, Hein Sprong, Marinus H J van Oers
Journal: The Lancet (2013)
Molecular Profiling of the Residual Disease of Triple-Negative Breast Cancers after Neoadjuvant Chemotherapy Identifies Actionable Therapeutic Targets
Authors: Justin M. Balko, Jennifer M. Giltnane, Kai Wang, Luis J. Schwarz, Christian D. Young, Rebecca S. Cook, Phillip Owens, Melinda E. Sanders, Maria G. Kuba, Violeta Sánchez, Richard Kurupi, Preston D. Moore, Joseph A. Pinto, Franco D. Doimi, Henry Gómez, Dai Horiuchi, Andrei Goga, Brian D. Lehmann, Joshua A. Bauer, Jennifer A. Pietenpol, Jeffrey S. Ross, Gary A. Palmer, Roman Yelensky, Maureen Cronin, Vincent A. Miller, Phillip J. Stephens, Carlos L. Arteaga
Journal: Cancer Discovery (2013)

Neoadjuvant chemotherapy (NAC) induces a pathologic complete response (pCR) in approximately 30% of patients with triple-negative breast cancers (TNBC). In patients lacking a pCR, NAC selects a subpopulation of chemotherapy-resistant tumor cells. To understand the molecular underpinnings driving treatment-resistant TNBCs, we performed comprehensive molecular analyses on the residual disease of 74 clinically defined TNBCs after NAC, including next-generation sequencing (NGS) on 20 matched pretreatment biopsies. Combined NGS and digital RNA expression analysis identified diverse molecular lesions and pathway activation in drug-resistant tumor cells. Ninety percent of the tumors contained a genetic alteration potentially treatable with a currently available targeted therapy. Thus, profiling residual TNBCs after NAC identifies targetable molecular lesions in the chemotherapy-resistant component of the tumor, which may mirror micrometastases destined to recur clinically. These data can guide biomarker-driven adjuvant studies targeting these micrometastases to improve the outcome of patients with TNBC who do not respond completely to NAC.This study demonstrates the spectrum of genomic alterations present in residual TNBC after NAC. Because TNBCs that do not achieve a CR after NAC are likely to recur as metastatic disease at variable times after surgery, these alterations may guide the selection of targeted therapies immediately after mastectomy before these metastases become evident.
Late-breaking abstract: Using eosinophilic phenotype to characterize asthma control
Authors: Ana Luisa Godoy Fernandes, Patricia Bueno Lima Fernandes, Maria Marta Amorim, Lilian Ballini Caetano, Ilka Santoro
Journal: European Respiratory Journal (2014)

BACKGROUND: Biomarkers of underlying respiratory disease activity occupy an important domain not only measure the structure/function, but also to provide information about inflammatory background. OBJETIVE: to compare the eosinophil cells count in blood and nasal samples with induced sputum cytology, characterize eosinophil phenotype. METHODS: 140 treated patients with moderate- severe asthma controlled based on ACQ5 scores were studied. Samples of nasal lavage, induced sputum and blood were collected at the same day. The nasal and blood eosinophilia were analyzed by ROC, Spearman9s correlation and logistic regression model. RESULTS: Based on ROC a cut-off point of nasal eosinophils of 4.5% and blood eosinophils, absolute and relative count, of 234/mm3 and 4.15%, respectively; giving a sensitivity of 72% for nasal eosinophils and 66% of blood eosinophils /mm3 and 52% of blood eosinophils %; a specificity of 96% of nasal, 65% and 78% of blood /mm3 and %, respectively. AUC was 89% for nasal-sputum comparisons, showing the accuracy of the nasal as the best predictor of sputum eosinophilia, when compared with blood eosinophils counts. After adjusting for age, gender and FEV1, the eosinophilic sputum was associated with 61 times increase in odds of eosinophils nasal count >5% (p
KRAS and BRAF Mutations Predict Primary Resistance to Imatinib in Gastrointestinal Stromal Tumors
Authors: Claudia Miranda, Martina Nucifora, Francesca Molinari, Elena Conca, Maria Chiara Anania, Andrea Bordoni, Piercarlo Saletti, Luca Mazzucchelli, Silvana Pilotti, Marco A. Pierotti, Elena Tamborini, Angela Greco, Milo Frattini
Journal: Clinical Cancer Research (2012)

Abstract Purpose: Gastrointestinal stromal tumors (GIST) are characterized by gain-of-function mutations in KIT/PDGFRA genes leading to a constitutive receptor activation which is well counteracted by imatinib. However, cases in which imatinib as first-line treatment has no effects are reported (primary resistance). Our purpose is to investigate alterations in downstream effectors, not reported so far in mutated GIST, possibly explaining the primary resistance to targeted treatments. Experimental Design: Two independent naive GIST cohorts have been analyzed for KIT, PDGFRA, KRAS, and BRAF mutations by direct sequencing. Cell lines expressing a constitutively activated and imatinib-responding KIT, alone or in combination with activated KRAS and BRAF, were produced and treated with imatinib. KIT receptor and its downstream effectors were analyzed by direct Western blotting. Results: In naive GISTs carrying activating mutations in KIT or PDGFRA a concomitant activating mutation was detected in KRAS (5%) or BRAF (about 2%) genes. In vitro experiments showed that imatinib was able to switch off the mutated receptor KIT but not the downstream signaling triggered by RAS–RAF effectors. Conclusions: These data suggest the activation of mitogen—activated protein kinase pathway as a possible novel mechanism of primary resistance to imatinib in GISTs and could explain the survival curves obtained from several clinical studies where 2% to 4% of patients with GIST treated with imatinib, despite carrying KIT-sensitive mutations, do not respond to the treatment. Clin Cancer Res; 18(6); 1769–76. ©2012 AACR.
Optimal Management of Clinical Stage I Nonseminoma: New Data for Patients to Consider
Authors: Ronald de Wit
Journal: Journal of Clinical Oncology (2014)

explanationisthateitherearlydefinitivetreatmentorwatchfulwaiting andchemotherapyatthetimeofdiseaserecurrencecuresnearly100% ofpatients.Therearenotrialdatathatproviderobustevidenceforthe superiority of one approach over the other. As a result, treatment choiceshavebeenguidedbyinstitutionalornationalconsensusrather than based on evidence. In 2006, in a special Urologic Oncology issue inJournalofClinicalOncology(JCO),areviewarticlewasdedicatedto this topic. 1 In the setting of CSIA NSGCT (lymphovascular invasion [LVI] absent in the primary tumor), the risk for occult metastatic spread is less than 20%, and there seems to be universal agreement to
Bcl-2 Blocks Cisplatin-Induced Apoptosis and Predicts Poor Outcome Following Chemoradiation Treatment in Advanced Oropharyngeal Squamous Cell Carcinoma
Authors: William A. Michaud, Anthony C. Nichols, Edmund A. Mroz, William C. Faquin, John R. Clark, Shahnaz Begum, William H. Westra, Hiroshi Wada, Paul M. Busse, Leif W. Ellisen, James W. Rocco
Journal: Clinical Cancer Research (2009)

This study aimed to test the hypothesis that elevated expression of antiapoptotic Bcl-2 family proteins predicts a poor therapeutic response of oropharyngeal squamous cell carcinoma (OPSCC) to concurrent platinum-based chemoradiation therapy.Levels of Bcl-2, Bcl-XL, and Bcl-w were determined and correlated with resistance to cisplatin in a large panel of cell lines derived from squamous cell carcinoma of the head and neck (HNSCC). Univariate and multivariate analyses were used to evaluate the relationship between Bcl-2 and Bcl-XL expression and disease-free survival following chemoradiation therapy in a uniformly treated cohort of patients with OPSCC.In HNSCC cell lines, high endogenous Bcl-2 expression was associated with increased cisplatin resistance, and experimental overexpression of Bcl-2 promoted cisplatin resistance. In patients, tumors positive for Bcl-2 before treatment had greater risk of treatment failure (hazard ratio, 5.99; 95% confidence interval, 1.73-20.8; P=0.0014). In contrast, endogenous Bcl-XL showed no correlation either with cisplatin sensitivity in the cell line panel in vitro, or with risk of recurrence in vivo (hazard ratio, 1.28; 95% confidence interval, 0.39-4.19; P=0.68). Associations between Bcl-2 expression and other clinical characteristics did not account for the predictive value of Bcl-2.Immunohistochemical assessment of Bcl-2 in pretreatment biopsy specimens can predict response of advanced OPSCC to concurrent platinum-based chemoradiation. As treatments targeting Bcl-2 and its family members become available, this immunohistochemical assessment could help personalize therapy by identifying a subpopulation of patients with a poor prognosis who might benefit from such treatments.
Mr Outside and Mr Inside: classic and alternative views on the pathogenesis of rheumatoid arthritis
Authors: G. Schett, G. S. Firestein
Journal: Annals of the Rheumatic Diseases (2010)

Different strategies can be applied to overcome an obstacle: one may either overcome it from the 'outside' or break it from the 'inside'. Similar strategies have been successfully used by two American football players in the 1940s, known as 'Mr Outside' and 'Mr Inside'. In this article, the authors propose similar concepts for initiating joint inflammation. Arthritis may start 'outside' as a primary inflammation of the synovial membrane (synovitis), which later spreads over to adjacent structures resulting in penetration into the bone marrow (outside-in concept). Alternatively, arthritis may start 'inside', in the bone marrow space, and later encroaches upon the synovium (inside-out concept). The authors discuss these two fundamentally different viewpoints on the pathogenesis of arthritis, each one of which bears attractive explanations for the mystery of the pathogenesis of arthritis.
Pertussis toxin treatment blocks hyperpolarization by muscarinic agonists in chick atrium.
Authors: S Sorota, Y Tsuji, T Tajima, A J Pappano
Journal: Circulation Research (1985)

Atrial and ventricular adenylate cyclase activity and atrial membrane potentials were measured in hearts from hatched chicks at 2-3 days after intravenous administration of pertussis toxin (0.5-1.0 micrograms, total) or saline. Both in atrium and ventricle, treatment with pertussis toxin antagonized inhibition by carbachol of basal and isoproterenol-stimulated adenylate cyclase activity without changing either basal or isoproterenol-stimulated adenylate cyclase. In atria from pertussis toxin-treated animals (5.4 mM potassium), carbachol hyperpolarized the resting membrane by 0.3 +/- 0.3 mV (n = 9) and did not increase resting potassium conductance. In contrast, carbachol hyperpolarized the resting membrane by 4.5 +/- 0.8 mV (n = 11) and increased resting potassium conductance more than 4-fold in saline-treated animals. Carbachol did not significantly affect the atrial action potential peak or duration at 50% repolarization of pertussis toxin-treated animals. This muscarinic agonist reduced action potential peak by 7.8 +/- 1.2 mV and the duration at 50% repolarization by 22.1 +/- 3.0 msec in atria from saline-treated animals. Pertussis toxin treatment also prevented the negative inotropic effect and the inhibition of calcium-dependent action potentials caused by carbachol in atrial muscle. Neither the affinity nor the maximal specific binding of [3H]quinuclidinyl benzilate in ventricular homogenates was changed by pertussis toxin treatment. The apparent affinity of carbachol for muscarinic receptor was slightly (approximately 2-fold) diminished in pertussis toxin-treated animals. The inhibition of carbachol-induced hyperpolarization by pertussis toxin treatment implicates a guanosine 5'-triphosphate-dependent protein (Ni or a similar protein) as an essential link that permits muscarinic receptor to regulate atrial potassium channels.
Metabolic syndrome increases the risk of liver cirrhosis in chronic hepatitis B
Authors: G L-H Wong, V W-S Wong, P C-L Choi, A W-H Chan, A M-L Chim, K K-L Yiu, H-Y Chan, F K-L Chan, J J-Y Sung, H L-Y Chan
Journal: Gut (2008)

<h3>Background:</h3> Metabolic syndrome is associated with non-alcoholic steatohepatitis and cryptogenic cirrhosis. Whether metabolic syndrome affects the severity of chronic hepatitis B (CHB) is unclear. <h3>Aim:</h3> We aimed to study the relationship between metabolic syndrome and the risk of liver cirrhosis in patients with CHB. <h3>Methods:</h3> We prospectively recruited patients with CHB from primary care and hospital clinics for liver stiffness measurement (LSM) with transient elastography to diagnose early cirrhosis. Probable cirrhosis was defined as LSM ⩾13.4 kPa. We analysed a subgroup of patients with paired LSM and liver biopsies to validate the accuracy of LSM. <h3>Results:</h3> 1466 patients had reliable LSM and 134 (9%) patients had adequate liver biopsy. 188 (13%) patients had metabolic syndrome. Histological liver cirrhosis was present in 32/134 (24%) patients. Histological liver cirrhosis was more common among patients who had metabolic syndrome (38%) versus those who did not (11%, p<i>&lt;</i>0.001). The specificity of probable cirrhosis on LSM for histological cirrhosis was 94%. Probable cirrhosis was present in 187 (13%) patients. Metabolic syndrome was more prevalent in patients with probable cirrhosis (24%) than those without cirrhosis (11%, p<i>&lt;</i>0.001). After adjustment for anthropometric, biochemical and virological factors, metabolic syndrome remained an independent factor associated with probable cirrhosis (odds ratio 1.7, 95% confidence interval (CI) 1.1 to 2.6). The odds ratios of probable cirrhosis were 1.4 (95% CI, 0.9 to 2.3), 2.6 (95% CI, 1.7 to 4.3), 4.1 (95% CI, 2.4 to 7.1), 4.0 (95% CI, 1.9 to 8.4) and 5.5 (95% CI, 1.8 to 16.7) in patients with one, two, three, four and five components of metabolic syndrome, respectively. <h3>Conclusion:</h3> Metabolic syndrome is an independent risk factor of liver cirrhosis in CHB.
APICAL ROTATION PLAYS A SIGNIFICANT ROLE IN DETERMINING LEFT VENTRICULAR DIASTOLIC FUNCTION: OBSERVATION DURING APICAL IMMOBILIZATION USING STARFISHTM POSITIONER
Authors: Mariko Iwasaki, Yumi Fukuta, Kasumi Masuda, Toshihiko Asanuma, Satoshi Nakatani
Journal: Journal of the American College of Cardiology (2010)
Salvage chemotherapy with alternating MINE–ESHAP regimen in relapsed or refractory Hodgkin’s lymphoma followed by autologous stem-cell transplantation
Authors: C. Fernández de Larrea, C. Martínez, A. Gaya, A. López-Guillermo, M. Rovira, F. Fernández-Avilés, M. Lozano, F. Bosch, J. Esteve, B. Nomdedeu, E. Montserrat, E. Carreras
Journal: Annals of Oncology (2009)
Short‐ to intermediate‐term follow‐up in patients treated with the combination of 311‐nm ultraviolet B phototherapy and biological agents
Authors: M. Inzinger, F.J. Legat, A. Hofer, W. Weger, A. Gruber‐Wackernagel, W. Salmhofer, P. Wolf
Journal: British Journal of Dermatology (2014)

Journal Article Short‐ to intermediate‐term follow‐up in patients treated with the combination of 311‐nm ultraviolet B phototherapy and biological agents Get access M. Inzinger, M. Inzinger Research Unit for Photodermatology Department of Dermatology Medical University of Graz Graz Austria Search for other works by this author on: Oxford Academic Google Scholar F.J. Legat, F.J. Legat Research Unit for Photodermatology Department of Dermatology Medical University of Graz Graz Austria Search for other works by this author on: Oxford Academic Google Scholar A. Hofer, A. Hofer Research Unit for Photodermatology Department of Dermatology Medical University of Graz Graz Austria Search for other works by this author on: Oxford Academic Google Scholar W. Weger, W. Weger Research Unit for Photodermatology Department of Dermatology Medical University of Graz Graz Austria Search for other works by this author on: Oxford Academic Google Scholar A. Gruber‐Wackernagel, A. Gruber‐Wackernagel Research Unit for Photodermatology Department of Dermatology Medical University of Graz Graz Austria Search for other works by this author on: Oxford Academic Google Scholar W. Salmhofer, W. Salmhofer Research Unit for Photodermatology Department of Dermatology Medical University of Graz Graz Austria Search for other works by this author on: Oxford Academic Google Scholar P. Wolf P. Wolf Research Unit for Photodermatology Department of Dermatology Medical University of Graz Graz Austria Correspondence: Peter Wolf. E‐mail: peter.wolf@medunigraz.at Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 171, Issue 4, 1 October 2014, Pages 915–917, https://doi.org/10.1111/bjd.12992 Published: 01 October 2014
Bosentan does not improve outcome in patients with steroid-resistant pulmonary sarcoidosis – Results from a double-blind placebo-controlled phase 2 trial
Authors: Katrin Hostettler, Florent Baty, Rebekka Kleiner, Lilian Junker, Michael Tamm, Martin Brutsche
Journal: European Respiratory Journal (2014)

Background: Sarcoidosis is a disorder of unknown etiology. Most patients improve under corticosteroid treatment, but side-effects and steroid-resistance underline the need for alternative treatments. Endothelin has fibrogenic activity, and the endothelin-system is activated in sarcoidosis. We studied the efficacy and safety of the endothelin receptor antagonist bosentan in sarcoidosis patients. Methods: In a prospective 12-month, double-blind, 1:1-randomized, placebo-controlled phase 2 trial, we assessed the effect of bosentan in patients with steroid-resistant sarcoidosis with impaired exercise capacity and/or resting lung function. Primary endpoints were safety and overall response rate of total lung capacity (TLC), diffusion capacity (DLCO), peak oxygen uptake (VO2peak), 6-minute walking distance (6MWD), and computed tomography (CT)-score. Secondary endpoints included adverse events and quality of life. Results: Twenty patients were randomized. Three patients discontinued the study medication prematurely. No serious drug-related adverse events occurred. At 12 months no statistically significant differences were observed in the primary endpoints including TLC, DLCO, 6MWD, VO2 peak, and CT-score. Sixty-three percent of the patients treated with bosentan showed an increase of 10% in at least one of the primary endpoints, compared to 67% in the placebo group (p=1). Conclusions: There is no evidence to support efficacy of bosentan as an antifibrotic treatment for patients with steroid-resistant pulmonary sarcoidosis. Bosentan was well tolerated and no drug-related adverse effects were observed within the study population.
THE TREATMENT OF CONVALESCENT SOLDIERS BY PHYSICAL MEANS
Authors: R. T. McKenzie
Journal: BMJ (1916)

TREATMENT OF CONVALESCENT SOLDIERS.[X Dzr= 215 posterior support, whether a gutter-shaped metal splint, or perforated zinc, or merely webbing slings, must be tightened up if this occurs.Within twelve to twenty-four hours it will be found that the extension straps are no longer taut-not becatgse they have slipped or stretched to any extent, as is proved by the tape measure, but because the muscles have relaxed.