tbuckley/cabot-search huggingface dataset:
Human agonistic TRAIL receptor antibodies Mapatumumab and Lexatumumab induce apoptosis in malignant mesothelioma and act synergistically with cisplatin
Authors: Larisa L Belyanskaya, Thomas M Marti, Sally Hopkins-Donaldson, Stefanie Kurtz, Emanuela Felley-Bosco, Rolf A Stahel
Journal: Molecular Cancer (2007)

Abstract Background The incidence of malignant pleural mesothelioma (MPM) is associated with exposure to asbestos, and projections suggest that the yearly number of deaths in Western Europe due to MPM will increase until 2020. Despite progress in chemo- and in multimodality therapy, MPM remains a disease with a poor prognosis. Inducing apoptosis by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) or agonistic monoclonal antibodies which target TRAIL-receptor 1 (TRAIL-R1) or TRAIL-R2 has been thought to be a promising cancer therapy. Results We have compared the sensitivity of 13 MPM cell lines or primary cultures to TRAIL and two fully human agonistic monoclonal antibodies directed to TRAIL-R1 (Mapatumumab) and TRAIL-R2 (Lexatumumab) and examined sensitization of the MPM cell lines to cisplatin-induced by the TRAIL-receptor antibodies. We found that sensitivity of MPM cells to TRAIL, Mapatumumab and Lexatumumab varies largely and is independent of TRAIL-receptor expression. TRAIL-R2 contributes more than TRAIL-R1 to death-receptor mediated apoptosis in MPM cells that express both receptors. The combination of cisplatin with Mapatumumab or Lexatumumab synergistically inhibited the cell growth and enhanced apoptotic death. Furthermore, pre-treatment with cisplatin followed by Mapatumumab or Lexatumumab resulted in significant higher cytotoxic effects as compared to the reverse sequence. Combination-induced cell growth inhibition was significantly abrogated by pre-treatment of the cells with the antioxidant N-acetylcysteine. Conclusion Our results suggest that the sequential administration of cisplatin followed by Mapatumumab or Lexatumumab deserves investigation in the treatment of patients with MPM.
Rehabilitation after coronary artery by-pass grafting and improved quality of life.
Authors: N A Hoad, I C Crawford
Journal: British Journal of Sports Medicine (1990)

Long waiting lists for coronary artery by-pass grafting often mean that patients have to endure a prolonged period of pre-operative disability, a known poor prognostic factor for their future quality of life and employment prospects. A survey of 60 patients who attended a post-operative rehabilitation course designed to restore their fitness and self-esteem, and hence their quality of life, has shown encouraging results. When questioned a mean 16 months later, 85 per cent are working and significant improvements have been seen in all four quality of life indicators assessed: job satisfaction, family life, social life and sex life. Significant improvements are also seen in their symptoms. Cardiac rehabilitation should be made more available following coronary artery by-pass grafting.
Fine needle aspiration of hepatic colorectal metastases: Fine needle aspiration has its place
Authors: Álvaro Sanz, María L del Valle
Journal: BMJ (2004)

Editor—Metcalfe et al underline the risks of fine needle aspiration cytology for hepatic colorectal metastases, but their proposed contraindication of fine needle aspiration and the possible diagnostic alternatives for liver lesions without apparent primary malignancy are not evidence …
Heterogeneity Maintenance in Glioblastoma: A Social Network
Authors: Rudy Bonavia, Maria-del-Mar Inda, Webster K. Cavenee, Frank B. Furnari
Journal: Cancer Research (2011)

Abstract Glioblastoma multiforme (GBM), the most common intracranial tumor in adults, is characterized by extensive heterogeneity at the cellular and molecular levels. This insidious feature arises inevitably in almost all cancers and has great significance for the general outcome of the malignancy, because it confounds our understanding of the disease and also intrinsically contributes to the tumor's aggressiveness and poses an obstacle to the design of effective therapies. The classic view that heterogeneity arises as the result of a tumor's “genetic chaos” and the more contemporary cancer stem cell (CSC) hypothesis tend to identify a single cell population as the therapeutic target: the prevailing clone over time in the first case and the CSC in the latter. However, there is growing evidence that the different tumor cell populations may not be simple bystanders. Rather, they can establish a complex network of interactions between each other and with the tumor microenvironment that eventually strengthens tumor growth and increases chances to escape therapy. These differing but complementary ideas about the origin and maintenance of tumor heterogeneity and its importance in GBM are reviewed here. Cancer Res; 71(12); 4055–60. ©2011 AACR.
Ungoutedly time for a change
Authors: Graham Reid
Journal: Annals of the Rheumatic Diseases (2015)

Dalbeth et al 1 report the findings of dual-energy CT (DECT) scanning in patients with asymptomatic hyperuricaemia and symptomatic gout. This report reinforces the need to change our terminology, classification and management guidelines for gout as Dalbeth et al 2 have already suggested in another study.

All current guidelines for the management of gout (recent review3) advise starting urate-lowering therapies for patients with …
Differences in the Transcriptional Response to Fulvestrant and Estrogen Deprivation in ER-Positive Breast Cancer
Authors: Neill Patani, Anita K. Dunbier, Helen Anderson, Zara Ghazoui, Ricardo Ribas, Elizabeth Anderson, Qiong Gao, Roger A'hern, Alan Mackay, Justin Lindemann, Robert Wellings, Jill Walker, Irene Kuter, Lesley-Ann Martin, Mitch Dowsett
Journal: Clinical Cancer Research (2014)

Abstract Purpose: Endocrine therapies include aromatase inhibitors and the selective estrogen receptor (ER) downregulator fulvestrant. This study aimed to determine whether the reported efficacy of fulvestrant over anastrozole, and high- over low-dose fulvestrant, reflect distinct transcriptional responses. Experimental Design: Global gene expression profiles from ERα-positive breast carcinomas before and during presurgical treatment with fulvestrant (n = 22) or anastrozole (n = 81), and corresponding in vitro models, were compared. Transcripts responding differently to fulvestrant and estrogen deprivation were identified and integrated using Gene Ontology, pathway and network analyses to evaluate their potential significance. Results: The overall transcriptional response to fulvestrant and estrogen deprivation was correlated (r = 0.61 in presurgical studies, r = 0.87 in vitro), involving downregulation of estrogen-regulated and proliferation-associated genes. The transcriptional response to fulvestrant was of greater magnitude than estrogen deprivation (slope = 0.62 in presurgical studies, slope = 0.63 in vitro). Comparative analyses identified 28 genes and 40 Gene Ontology categories affected differentially by fulvestrant. Seventeen fulvestrant-specific genes, including CAV1/2, SNAI2, and NRP1, associated with ERα, androgen receptor (AR), and TP53, in a network regulating cell cycle, death, survival, and tumor morphology. Eighteen genes responding differently to fulvestrant specifically predicted antiproliferative response to fulvestrant, but not anastrozole. Transcriptional effects of low-dose fulvestrant correlated with high-dose treatment, but were of lower magnitude (ratio = 0.29). Conclusions: The transcriptional response to fulvestrant has much in common with estrogen deprivation, but is stronger with distinctions potentially attributable to arrest of estrogen-independent ERα activity and involvement of AR signaling. Genes responding differently to fulvestrant may have predictive utility. These data are consistent with the clinical efficacy of fulvestrant versus anastrozole and higher dosing regimens. Clin Cancer Res; 20(15); 3962–73. ©2014 AACR.
Real-time quantitative RT–PCR and detection of tumour cell dissemination in breast cancer patients: plasmid versus cell line dilutions
Authors: M. Saad Ismail, W. Wynendaele, J.L.E. Aerts, R. Paridaens, L. Van Mellaert, J. Anné, R. Gaafar, N. Shakankiry, H.M. Khaled, M.R. Christiaens, S. Omar, P. Vandekerckhove, A.T. van Oosterom
Journal: Annals of Oncology (2003)
Pharmacological treatment of abdominal aortic aneurysm
Authors: T. Miyake, R. Morishita
Journal: Cardiovascular Research (2009)

Abdominal aortic aneurysm (AAA) is a common degenerative condition with high mortality in older men. Elective surgical or endovascular repair is performed to prevent rupture of large AAAs. In contrast, despite gradual expansion, small AAAs have a low risk of rupture, and there is currently no well-defined treatment strategy for them. Therefore, a pharmacological approach for AAA is expected in the clinical setting. Indeed, several therapeutic effects of pharmacological agents have been reported in experimental models, and some agents have undergone clinical trials. Treatment with statins, angiotensin-converting enzyme-inhibitors, antibiotics, and anti-inflammatory agents appears to inhibit the growth rate of AAA in humans. However, as the sample size and follow-up period were limited in these studies, a large randomized study with long-term follow-up of small AAA should be performed to clarify the effect of these agents. Recently, the regression of AAA using molecular pharmacological approaches was reported in experimental studies. The characteristics of these strategies are the regulation of multiple molecular mediators and the signalling networks associated with AAA formation. On the basis of the results of these investigations, it may be possible to repair the injured aortic wall and obtain the remission of AAA using pharmacological therapy.
Caspase-8: Fly or Die
Authors: Steven M. Frisch
Journal: Cancer Research (2008)

Abstract Recent studies have revealed that procaspase-8 has an important function in cell adhesion and motility. Src phosphorylation controls this function by preventing the conversion of procaspase-8, which is an adhesion/migration factor, to mature caspase-8, which is an apoptosis-inducing factor. This provides a mechanism to switch these opposing functions. In its migratory role, procaspase-8 interacts with the phosphatidylinositol-3-OH kinase regulatory subunit p85α and c-src to modulate signaling by Rac and extracellular signal-regulated kinase, and promote calpain activation. Here, I survey the findings of these studies and discuss potential mechanisms and ramifications for cancer prognosis and therapy. [Cancer Res 2008;68(12):4491–3]
KL-6 levels are elevated in plasma from patients with acute respiratory distress syndrome
Authors: H. Sato, M.E.J. Callister, S. Mumby, G.J. Quinlan, K.I. Welsh, R.M. duBois, T.W. Evans
Journal: European Respiratory Journal (2003)

The acute respiratory distress syndrome (ARDS) is an extreme form of lung injury characterised by disruption to the alveolar epithelium. KL-6 is a mucin-like glycoprotein expressed on type II pneumocytes. Circulating levels of KL-6 have diagnostic and prognostic significance in a number of interstitial lung diseases, and when elevated are thought to indicate disruption of the alveolar epithelial lining. In this study, the authors sought to determine whether plasma KL-6 levels were elevated in patients with ARDS and whether these were associated with aetiology, disease severity, outcome or ventilatory strategy. Plasma samples were collected from 28 patients with ARDS, nine ventilated controls of matched illness severity and 10 healthy individuals. KL-6 concentrations were measured by enzyme-linked immunosorbent assay. Patients with ARDS had higher plasma levels of KL-6 (median 537 U x mL(-1), interquartile range (IQR) 383-1,119), as compared to ventilated controls (median 255 U x mL(-1), IQR 83-338) and normal individuals (median 215 U x mL(-1), IQR 149-307). In patients with ARDS, plasma KL-6 levels were higher in nonsurvivors than survivors, and correlated positively with oxygenation index and negatively with arterial oxygen tension:inspiratory oxygen fraction ratio. There were also significant positive correlations with mean and peak airway pressures. Elevated levels of plasma KL-6 may provide a useful marker for acute respiratory distress syndrome in ventilated patients and have possible prognostic significance. Alveolar epithelial cell damage may be influenced by the nature of mechanical ventilatory support.
EAACI position paper: irritant‐induced asthma
Authors: O. Vandenplas, M. Wiszniewska, M. Raulf, F. de Blay, R. Gerth van Wijk, G. Moscato, B. Nemery, G. Pala, S. Quirce, J. Sastre, V. Schlünssen, T. Sigsgaard, A. Siracusa, S. M. Tarlo, V. van Kampen, J.‐P. Zock, J. Walusiak‐Skorupa
Journal: Allergy (2014)

Abstract The term irritant‐induced (occupational) asthma ( IIA ) has been used to denote various clinical forms of asthma related to irritant exposure at work. The causal relationship between irritant exposure(s) and the development of asthma can be substantiated by the temporal association between the onset of asthma symptoms and a single or multiple high‐level exposure(s) to irritants, whereas this relationship can only be inferred from epidemiological data for workers chronically exposed to moderate levels of irritants. Accordingly, the following clinical phenotypes should be distinguished within the wide spectrum of irritant‐related asthma: (i) definite IIA , that is acute‐onset IIA characterized by the rapid onset of asthma within a few hours after a single exposure to very high levels of irritant substances; (ii) probable IIA , that is asthma that develops in workers with multiple symptomatic high‐level exposures to irritants; and (iii) possible IIA , that is asthma occurring with a delayed‐onset after chronic exposure to moderate levels of irritants. This document prepared by a panel of experts summarizes our current knowledge on the diagnostic approach, epidemiology, pathophysiology, and management of the various phenotypes of IIA .
Ventilatory parameters on cardiopulmonary exercise testing in advanced heart failure: Chagas versus ischemic etiology
Authors: Laura Maria Tomazi Neves, Alexandra Corrêa Gervazoni Balbuena de Lima, Maria Estefânia Bosco Otto, Marianne Lucenna da Silva, Vinícius Zacarias Maldaner da Silva, Cláudio Hiroshi Nakata, Filippe Vargas de Siqueira Campos, Fellipe Amatuzzi Teixeira, Ross Arena, Gerson Cipriano Júnior
Journal: European Respiratory Journal (2014)

Background: A hallmark symptom of heart failure (HF) is breathlessness and a potential cause is the reduced ventilatory efficiency . Exercise capacity (EC), expressed as peak oxygen consumption (VO2peak), is one of the best predictors of prognosis in HF. Nevertheless, the exercise ventilatory response in Chagas has not been fully comprehended.  Objective:To examine the relationship between exercise ventilation indices and EC on cardiopulmonary exercise testing (CPX) in Chagas (CH) and Ischemic (IS) HF cohorts as well as healthy controls (HC).  Methods: Fifty-eight male HF patients (31 IS and 27 CH) and 19 HC matched by age (p=0,30) and body mass index (p=0,17) were included in this analysis. Patients with with IS or CH etiology in current standard medical therapy use underwent symptom limited CPX in treadmill. Patients with pulmonary disease were excluded.  Results: HF patients presented LV systolic disfunction (p=0,14), lower peak VO2 (IS: 20,2+/-7,6ml/kg.min and CH: 20,7+/-8,6ml/kg.min, p=0,97), lower VE (IS: 50,9+/-16,9ml/min, CH: 54,7+/-19,4 ml/min, p= 0,63); higher ventilatory reserve (VR) (IS: 93,3+/-23,3ml/min; CH: 78,8+/-18,3ml/min, p=0,024) signficant diferent comparing to control group (all p  Conclusions: In patients with advanced HF, IS or CH etiology, EC was inversely related to VR. Exercise breathlessness seems to be related to inefficiency using of VR. This reinforces the importance of specific respiratory muscles training in HF.
Sirolimus-eluting stent implantation for unprotected left main coronary artery stenosis
Authors: Seung-Jung Park, Young-Hak Kim, Bong-Ki Lee, Seung-Whan Lee, Cheol Whan Lee, Myeong-Ki Hong, Jae-Joong Kim, Gary S. Mintz, Seong-Wook Park
Journal: Journal of the American College of Cardiology (2005)
Interleukin-33 Induces Protective Effects in Adipose Tissue Inflammation During Obesity in Mice
Authors: Ashley M. Miller, Darren L. Asquith, Axel J. Hueber, Lesley A. Anderson, William M. Holmes, Andrew N. McKenzie, Damo Xu, Naveed Sattar, Iain B. McInnes, Foo Y. Liew
Journal: Circulation Research (2010)

Chronic low-grade inflammation involving adipose tissue likely contributes to the metabolic consequences of obesity. The cytokine interleukin (IL)-33 and its receptor ST2 are expressed in adipose tissue, but their role in adipose tissue inflammation during obesity is unclear.To examine the functional role of IL-33 in adipose tissues and investigate the effects on adipose tissue inflammation and obesity in vivo.We demonstrate that treatment of adipose tissue cultures in vitro with IL-33 induced production of Th2 cytokines (IL-5, IL-13, IL-10) and reduced expression of adipogenic and metabolic genes. Administration of recombinant IL-33 to genetically obese diabetic (ob/ob) mice led to reduced adiposity, reduced fasting glucose and improved glucose and insulin tolerance. IL-33 also induced accumulation of Th2 cells in adipose tissue and polarization of adipose tissue macrophages toward an M2 alternatively activated phenotype (CD206(+)), a lineage associated with protection against obesity-related metabolic events. Furthermore, mice lacking endogenous ST2 fed high-fat diet had increased body weight and fat mass and impaired insulin secretion and glucose regulation compared to WT controls fed high-fat diet.In conclusion, IL-33 may play a protective role in the development of adipose tissue inflammation during obesity.
Cardiovascular Drug Use and Hospitalizations Attributable to Type 2 Diabetes
Authors: Joëlle A. Erkens, Olaf H. Klungel, Ronald P. Stolk, José A. Spoelstra, Diederick E. Grobbee, Hubert G.M. Leufkens
Journal: Diabetes Care (2001)

OBJECTIVE—To investigate cardiovascular drug use and hospitalizations attributable to type 2 diabetes from 1 year before until 6 years after the start of oral antidiabetic therapy. RESEARCH DESIGN AND METHODS—In this cohort study, 2,584 patients with type 2 diabetes were selected from the PHARMO Record Linkage System, comprising pharmacy records and hospitalizations for all 320,000 residents of six Dutch cities. Patients with type 2 diabetes were identified as incident oral antidiabetic drug users between 1992 and 1997. Nondiabetic subjects were 1:1–matched for age, sex, pharmacy, and index date and received no insulin, oral antidiabetic drugs, or glucose-testing supplies. RESULTS—Patients with type 2 diabetes were more likely to use cardiovascular drugs (RR 1.28 [95% CI 1.23–1.34]) and to be hospitalized because of cardiovascular diseases (1.54 [1.33–1.78]) after the start of oral antidiabetic therapy than nondiabetic subjects. Differences between patients with type 2 diabetes and nondiabetic subjects lessened from 1 year before until 6 years after the start of oral antidiabetic therapy, reflected by decreasing attributable risks for diuretics, β-blockers, calcium channel blockers, and cardiac and antithrombotic drugs. The difference in use of angiotensin-converting enzyme inhibitors and lipid-lowering drugs increased. Cardiovascular hospitalizations attributable to type 2 diabetes were ∼50% in the years close to the start of oral antidiabetic treatment and decreased to ∼33% in the following years. CONCLUSIONS—Although cardiovascular drug use and hospitalizations remained increased in patients with type 2 diabetes after the start of oral antidiabetic therapy, cardiovascular drug use attributable to type 2 diabetes decreased after the start of oral antidiabetic therapy, especially β-blockers, whereas cardiovascular hospitalizations first decreased and then stabilized.
High altitude medicine in China in the 21st century: opportunities and challenges
Authors: Lan Huang
Journal: Military Medical Research (2014)

China has the largest plateau, Qinghai-Tibet Plateau, where inhabited the most high altitude populations. Moreover, millions of people from plain areas come to the plateau for travel and work purposes and the number of the newcomers has been increasing every year. The hypoxic environment of plateau raised a series of related health issues in the new immigrants, so have created a special medical discipline - High Altitude Medicine. Over the past decades, researches on high altitude medicine have never being ceased in China, and lots of research findings have been reported. Application and practice of these achievements have greatly decreased the mobility and mortality of high-altitude diseases, however, there remained lots of questions to be elucidated. In view of this, the authors were granted a special project from the National Health and Family Planning Commission of China, and conducted a multi-center, prospective, on-scene high altitude medicine study for the acute mountain sickness. Some innovative findings were achieved, and the parameters for diagnosis and application conditions were proposed. Furthermore, the different diagnoses and treatment effects were compared, and a more standardized, reasonable scheme was drawn up. Regarding the unbalanced medical resources in the vast high altitude area, an application system for the public and the army has been established. In the 21st century, innovations in China and novel research approaches have provided great opportunities for the development of high altitude medicine. It is believed that the researchers in China are able to catch the opportunities and address the challenges.
Incidence of Stroke in Paroxysmal Versus Sustained Atrial Fibrillation in Patients Taking Oral Anticoagulation or Combined Antiplatelet Therapy
Authors: Stefan H. Hohnloser, Dimitri Pajitnev, Janice Pogue, Jeff S. Healey, Marc A. Pfeffer, Salim Yusuf, Stuart J. Connolly
Journal: Journal of the American College of Cardiology (2007)
Increased plasma viscosity as a reason for inappropriate erythropoietin formation.
Authors: A Singh, K U Eckardt, A Zimmermann, K H Götz, M Hamann, P J Ratcliffe, A Kurtz, W H Reinhart
Journal: Journal of Clinical Investigation (1993)

The aim of this study was to examine whether altered plasma viscosity could contribute to the inappropriately low production rate of erythropoietin (EPO) observed in patients suffering from hypergammaglobulinemias associated with multiple myeloma or Waldenström's disease. We found that the EPO formation in response to anemia in these patients was inversely related to plasma viscosity. A similar inverse relationship between plasma viscosity and EPO production was seen in rats in which EPO formation had been stimulated by exchange transfusion and the plasma viscosity of which was thereby altered by using exchange solutions of different composition to alter plasma viscosity and thus whole blood viscosity independently from hematocrit. Raising the gammaglobulin concentration to approximately 40 mg/ml plasma in the rats almost totally blunted the rise in serum EPO levels despite a fall of the hematocrit to 20%. Determination of renal EPO mRNA levels by RNase protection revealed that the reductions in serum EPO levels at higher plasma viscosities were paralleled by reductions in renal EPO mRNA levels. Taken together, our findings suggest that plasma viscosity may be a significant inhibitory modulator of anemia-induced EPO formation. The increased plasma viscosity in patients with hypergammaglobulinemias may therefore contribute to the inappropriate EPO production, which is a major reason for the anemia developing in these patients.