tbuckley/cabot-search huggingface dataset:
Purging of the Neuroblastoma Stem Cell Compartment and Tumor Regression on Exposure to Hypoxia or Cytotoxic Treatment
Authors: Ilaria Marzi, Massimo D'Amico, Tiziana Biagiotti, Serena Giunti, Maria Vittoria Carbone, David Fredducci, Enzo Wanke, Massimo Olivotto
Journal: Cancer Research (2007)

Abstract We worked out an experimental protocol able to purge the stem cell compartment of the SH-SY5Y neuroblastoma clone. This protocol was based on the prolonged treatment of the wild-type cell population with either hypoxia or the antiblastic etoposide. Cell fate was monitored by immunocytochemical and electrophysiologic (patch-clamp) techniques. Both treatments produced the progressive disappearance of neuronal type (N) cells (which constitute the bulk of the tumor), leaving space for a special category of epithelial-like substrate-adherent cells (S0). The latter represent a minimal cell component of the untreated population and are endowed with immunocytochemical markers (p75, c-kit, and CD133) and the electrophysiologic “nude” profile, typical of the neural crest stem cells. S0 cells displayed a highly clonogenic potency and a substantial plasticity, generating both the N component and an alternative subpopulation terminally committed to the fibromuscular lineage. Unlike the N component, this lineage was highly insensitive to the apoptotic activity of hypoxia and etoposide and developed only when the neuronal option was abolished. Under these conditions, the fibromuscular progeny of S0 expanded and progressed up to the exhaustion of the staminal compartment and to the extinction of the tumor. When combined, hypoxia and etoposide cooperated in abolishing the N cell generation and promoting the conversion of the tumor described. This synergy might mirror a natural condition in the ischemic areas occurring in cancer. These results have relevant implications for the understanding of the documented tendency of neuroblastomas to regress from a malignant to a benign phenotype, either spontaneously or on antiblastic treatment. [Cancer Res 2007;67(6):2402–7]
Overcoming Resistance to Conventional Drugs in Ewing Sarcoma and Identification of Molecular Predictors of Outcome
Authors: Katia Scotlandi, Daniel Remondini, Gastone Castellani, Maria Cristina Manara, Filippo Nardi, Lara Cantiani, Mirko Francesconi, Mario Mercuri, Anna Maria Caccuri, Massimo Serra, Sakari Knuutila, Piero Picci
Journal: Journal of Clinical Oncology (2009)

The improvement of Ewing sarcoma (EWS) therapy is currently linked to the discovery of strategies to select patients with poor and good prognosis and of modified treatment regimens. In this study, we analyzed the molecular factors governing EWS response to chemotherapy to identify genetic signatures to be used for risk-adapted therapy.Microarray technology was used for profiling 30 primary tumors and seven metastases of patients who were classified according to event-free survival. For selected genes, real-time polymerase chain reaction was applied in 42 EWS primary tumors as validation assay. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test was used to evaluate in vitro drug sensitivity.We identified molecular signatures that reflect tumor resistance to chemotherapy. Annotation analysis was applied to reveal the biologic functions that critically influenced clinical outcome. The prognostic relevance of glutathione metabolism pathway was validated. The expression of MGST1, the microsomal glutathione S-transferase (GST), was found to clearly predict EWS prognosis. MGST1 expression was associated with doxorubicin chemosensitivity. This prompted us to assess the in vitro effectiveness of 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol (NBDHEX), a new anticancer agent that efficiently inhibits GST enzymes. Six cell lines were found to be sensitive to this new drug.Classification of EWS patients into high- and low-risk groups is feasible with restricted molecular signatures that may have practical value at diagnosis for selecting patients with EWS who are unresponsive to current treatments. Glutathione metabolism pathway emerged as one of the most significantly altered prognosis-associated pathway. NBDHEX is proposed as a new potential therapeutic possibility.
The Function of AID in Somatic Mutation and Class Switch Recombination
Authors: Katrin F. Chua, Frederick W. Alt, John P. Manis
Journal: The Journal of Experimental Medicine (2002)

The immune system has evolved specific mechanisms to combat a potentially limitless number of foreign pathogens using a limited arsenal of Ig genes. To diversify the coding potential of the Ig genes, B cells undergo several processes of regulated genetic alterations. Early in their development, B
Atrial Fibrillation Ablation Using a Robotic Catheter Remote Control System
Authors: Walid Saliba, Vivek Y. Reddy, Oussama Wazni, Jennifer E. Cummings, J. David Burkhardt, Michel Haissaguerre, Josef Kautzner, Petr Peichl, Petr Neuzil, Volker Schibgilla, Georg Noelker, Johannes Brachmann, Luigi Di Biase, Conor Barrett, Pierre Jais, Andrea Natale
Journal: Journal of the American College of Cardiology (2008)
Recent advances and novel agents for gastrointestinal stromal tumor (GIST)
Authors: Gurpreet Lamba, Samir Ambrale, Byung Lee, Ridhi Gupta, Shamudheen M Rafiyath, Delong Liu
Journal: Journal of Hematology & Oncology (2012)

Abstract The discovery of CD117 mutation in almost all gastrointestinal stromal tumors (GISTs) marked a milestone. Other spindle cell neoplasms arising from the GI tract including lipoma, schwannoma, hemangioma, leiomyoma, and leiomyosarcoma are typically CD117-negative. GIST research and clinical care now represent a paradigm of translating discoveries in the molecular pathogenesis of cancer into highly effective targeted therapies that selectively inhibit etiologic “driver” pathways, leading to dramatically improved clinical outcomes. A series of investigations and trials are underway to develop novel and effective ways to treat patients with GIST. In this review, we discuss the highlights of recent advances and novel agents for GIST therapy.
Biomarkers of Resistance to Epidermal Growth Factor Receptor Monoclonal Antibodies in Patients with Metastatic Colorectal Cancer
Authors: Michaela S. Banck, Axel Grothey
Journal: Clinical Cancer Research (2009)

Abstract Genomics and proteomics have held out the promise of individualized medicine for the last 10 or 20 years, but clinical medicine has not yet delivered on this promise. Some cancers, such as breast cancer and some hematologic malignancies, have been at the forefront of individualized therapeutic approaches by integrating molecular biomarkers into treatment decision algorithms. Until recently, the treatment of colorectal cancer (CRC) has lagged behind these other cancers in this regard and therapeutic decisions have been solely empirical. Data from various clinical trials and translational studies have now opened the door for individualized treatment approaches by identifying patients with metastatic CRC who are most likely to benefit from antibodies against the epidermal growth factor receptor (EGFR), cetuximab and panitumumab. Activating mutations of KRAS, a downstream mediator of EGFR signaling, has been shown to render EGFR antibodies ineffective, such that analyzing tumors for these mutations has become mandatory before the use of EGFR antibodies is considered in CRC. Beyond KRAS, several additional biomarkers are currently being investigated as potential positive or negative predictors for the efficacy of EGFR-targeted therapy. Most of these markers are alterations of molecules integrated in the EGFR pathway. This review will focus on the type and quality of evidence that has been gathered to date to predict resistance to monoclonal antibodies against EGFR in CRC. (Clin Cancer Res 2009;15(24):7492–501)
Asbestos, asbestosis, and lung cancer: a critical assessment of the epidemiological evidence
Authors: P A Hessel
Journal: Thorax (2005)

The question of whether lung cancer can be attributed to asbestos exposure in the absence of asbestosis remains controversial. Nine key epidemiological papers are reviewed in a point/counterpoint format, giving the main strengths and limitations of the evidence presented. Of the nine papers, two concluded that asbestosis was necessary and seven that it was not. However, the study design, nature and circumstances of exposure and method of analysis of the studies differed considerably, and none was considered definitive. It is concluded that, because of the relative insensitivity of chest radiography and the uncertain specificity of findings from histological examinations or computed tomography, it is unlikely that epidemiology alone can put either the strict scientific or practical medicolegal questions beyond doubt. It is probable that the issue may depend critically on asbestos fibre type, an aspect not so far addressed.
Randomized, double-blind, placebo-controlled trial of autologous blood therapy for atopic dermatitis
Authors: M.H. Pittler, N.C. Armstrong, A. Cox, P.M. Collier, A. Hart, E. Ernst
Journal: British Journal of Dermatology (2003)

Summary Background Autologous blood therapy (ABT) is used for treating atopic dermatitis (AD) in some European countries and is promoted on internet sites for this condition. However, there is little evidence from rigorous clinical trials to suggest that it is effective. Objectives To test the effectiveness of ABT for the symptomatic treatment of patients with AD. Methods Fifty subjects responded to press advertisements, and 31 were randomized within strata of severity at recruitment. Patients were included into a double‐blind, placebo‐controlled trial and received ABT or placebo once weekly for 5 weeks. Assessments were performed at baseline, at weekly intervals and after a 5‐week follow up. The Six Area, Six Sign AD (SASSAD) severity index was predefined as the primary outcome measure. The Dermatology Life Quality Index and patient ratings of pruritus, quality of sleep and skin appearance on 100‐mm visual analogue scales were defined as secondary outcome measures. Success of patient blinding and adverse events were assessed. Results Data were analysed on an intention‐to‐treat basis. Analysis of covariance suggested a significant differential change of the SASSAD score between baseline and the end of the follow‐up period in favour of ABT. The mean reduction in SASSAD score was 13·5 points (95% confidence interval, CI 6·6–20·4, P < 0·001) over and above placebo; the corresponding value at the end of treatment was 9·6 (95% CI 4·2–14·9, P = 0·001). No clear significant intergroup differences in any of the secondary outcome measures were found. Six patients in the ABT group and seven in the placebo group reported minor and transient adverse events. Conclusions These data suggest that, according to the SASSAD score, ABT has beneficial effects in the treatment of AD, although this was not confirmed by the patient‐rated assessments. The improvement in observer‐rated skin condition suggested by this study needs confirmation in larger trials.
Effect of Changing Heart Rate on Cardiovascular Function in the Conscious Dog
Authors: MARK I. M. NOBLE, DIANA TRENCHORD, ABRAHAM GUZ
Journal: Circulation Research (1966)

The effect of heart rate on the cardiovascular system of the conscious dog was studied by pacing the heart with an implanted right atrial electrode. Left ventricular outflow was measured by an electromagnetic flowmeter with a chronically implanted transducer on the ascending aorta. As heart rate increased, stroke volume fell, and this was linearly related to heart rate over the entire range studied. Peak flow rate and maximum acceleration decreased as heart rate increased, but the change was small compared with that in stroke volume. The decrease in stroke volume resulted principally from a loss of volume ejected in late systole. An increase in heart rate sometimes resulted in a rise of cardiac output, and when this occurred mean arterial pressure rose; when cardiac output did not increase, mean arterial pressure also remained unchanged. The data suggest that there is a pressure for the systemic circulation analogous to the "critical closing pressure" of peripheral vascular beds. It was shown that in these circumstances changes in calculated systemic resistance may not reflect any real alterations in the peripheral vascular beds.
Cellular and molecular features of lipoma tissue: comparison with normal adipose tissue
Authors: H. Suga, H. Eto, K. Inoue, N. Aoi, H. Kato, J. Araki, T. Higashino, K. Yoshimura
Journal: British Journal of Dermatology (2009)

Involvement of adipose-derived stem/progenitor/stromal cells (ASCs) in the development of lipomas has been suggested, but the pathogenesis and pathophysiology of this tumour remain unclear.To analyse cellular and transcriptional characteristics of lipoma tissue compared with normal adipose tissue, further to delineate differentiating features.For lipoma or normal adipose tissues, we used a new whole-mount staining enabling three-dimensional imaging of nonfixed and nonfrozen adipose tissue. Immunohistochemistry and real-time polymerase chain reaction for obesity-related genes were performed as well as comparative assay of the proliferative and adipogenic capacity of ASCs.A large number of small adipocytes surrounded by CD34+/lectin- ASCs and increased numbers of Ki67+/CD34+ ASCs indicated enhanced adipogenesis in lipoma compared with normal adipose tissue. In contrast, cellular apoptosis was not enhanced in lipoma, suggesting that the enlargement of lipoma tissue may be due to a positive balance of adipocyte turnover (accelerated adipogenesis combined with nonenhanced apoptosis). Leptin mRNA was upregulated in lipoma, while adiponectin, tumour necrosis factor-alpha and glucose transporter 1 mRNA were downregulated and there were no apparent changes in hypoxia-inducible factor 1alpha, peroxisome proliferator-activated receptor-gamma and plasminogen activator inhibitor-1. These results suggested dysfunction of lipoma adipocytes similar to that in obesity, but indicated that lipoma tissue lacked several obesity-related phenomena such as ischaemia (hypoxia), macrophage infiltration, inflammatory reactions and enhanced glycolysis. ASCs from lipoma and normal adipose tissue showed similar proliferative and adipogenic capacity.Our findings revealed that lipoma tissue shows a positive balance of adipocyte turnover involving proliferating ASCs and several transcriptional differences from adipose tissue enlargement in obesity.
Emerging Biology of Malignant Salivary Gland Tumors Offers New Insights into the Classification and Treatment of Mucoepidermoid Cancer
Authors: Frederic J. Kaye
Journal: Clinical Cancer Research (2006)

In this issue of Clinical Cancer Research , Okabe et al. ([1][1]) have analyzed 71 cases of mucoepidermoid cancer and 51 cases of non-mucoepidermoid cancer for the presence of the Mect1-Maml2 fusion oncogene and have made a valuable observation. They confirmed that Mect1-Maml2 expression is specific
Prospective Randomized Comparison of Thoracoscopic Talc Poudrage under Local Anesthesia versus Bleomycin Instillation for Pleurodesis in Malignant Pleural Effusions
Authors: ANDREAS H. DIACON, CHRISTOPH WYSER, CHRISTOPH T. BOLLIGER, MICHAEL TAMM, MIKLOS PLESS, ANDRÉ P. PERRUCHOUD, MARKUS SOLÈR
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Induction of pleurodesis offers benefit for patients with metastatic tumors and symptomatic malignant pleural effusions, but the best method for achieving this is still unknown. In this prospective, randomized comparison of two well-established pleurodesis procedures, 36 patients with malignant pleural effusions, expanded lungs after drainage, and expected survival of > 1 mo received either bleomycin instillation (60E) via a small-bore thoracostomy tube or thoracoscopic talc poudrage (5 g) under local anesthesia. Efficacy, safety, and cost could be evaluated for 32 treatments (17 bleomycin, 15 talc) in 31 patients. Recurrence rates of effusion with bleomycin and talc poudrage after 30 d were 41% and 13% (p = 0.12), respectively, those after 90 d were 59% and 13%, respectively (p = 0.01), and those after 180 d were 65% and 13% (p = 0.005), respectively. Neither procedure showed any major adverse effect, and both were equally well tolerated. Cost estimation favored thoracoscopic talc poudrage, both for the initial hospitalization and with regard to recurrences. In conclusion, thoracoscopic talc pleurodesis under local anesthesia is superior to bleomycin instillation for pleurodesis in cases of malignant pleural effusion.
The Effects of International Monetary Fund Loans on Health Outcomes
Authors: Megan Murray, Gary King
Journal: PLoS Medicine (2008)

Founded in the wake of the Great Depression of the 1930s, the International Monetary Fund (IMF) was established in 1945 when government representatives met and agreed on a “framework of international economic cooperation” (http://www.imf.org/external/ index.htm) designed to prevent future economic crises. Its mission was threefold: to ensure the stability of the exchange rate, to promote economic growth, and to provide financial assistance in the form of shortterm loans to countries experiencing balance-of-payments difficulties. When countries borrow from the Fund, they are required to agree to conditions set by the organization, a process that the IMF refers to as “conditionality.” These conditions entail the adoption of economic policies or “structural adjustment programs” that are meant to redress the problems that led to the need for the loan and therefore to enable prompt repayment. While the conditions vary for different loans, most impose some regimen of fiscal austerity through reduced government spending, removing barriers to international trade, cutting government subsidies, and privatization.
Who are the young professionals working in the field of rheumatology in Europe and what are their needs? An EMEUNET (EMerging EUlar NETwork) survey
Authors: C Gaujoux-Viala, R Knevel, P Mandl, G Nagy, M Frank, P Machado, G Hatemi, MH Buch, D Aletaha, L Gossec
Journal: Annals of the Rheumatic Diseases (2012)

One of the eight objectives set by the European League Against Rheumatism (EULAR)for 2012 is to ‘bring on board high quality, young generation contributors in all EULAR activities’. This statement was the backbone for the development, in 2010, of the EMerging EUlar NETwork (EMEUNET) group, representing a Europe-wide network of young rheumatologists.1 Its key objectives include promoting and facilitating a comprehensive higher educational platform for rheumatology trainees and supporting aspiring young academics/scientists throughout Europe to maintain excellence in rheumatology research.

In order to achieve this, a first and necessary step was to obtain a better understanding of the current young professionals working in the field of rheumatology in Europe: to define the demographics of rheumatology trainees and scientists, the setting of their respective …
Today's lifestyles, tomorrow's cancers: trends in lifestyle risk factors for cancer in low- and middle-income countries
Authors: V.A. McCormack, P. Boffetta
Journal: Annals of Oncology (2011)

BackgroundThe global burden of cancer is projected to increase from 13.3 to 21.4 million incident cases between 2010 and 2030 due to demographic changes alone, dominated by a growing burden in low- and middle-income countries (LMICs). Lifestyle risk factors for cancer are also changing in these countries and may further influence this burden.DesignWe consider examples of changes already occurring in population-level distributions of tobacco and alcohol consumption, body weight, and reproductive lives of women to gauge the magnitude of their projected impact on cancer incidence in future decades.ResultsTrends in lifestyle factors vary greatly between settings and by sex. Some common trends point to considerable increases in cancers of the (i) lung in men due to tobacco smoking; (ii) upper aerodigestive tract (UADT) due to increasing tobacco and alcohol consumption, worse in men; (iii) colon from increasing body mass index, and alcohol and tobacco consumption; and (iv) in women, breast due particularly to consistent international trends of younger age at menarche, smaller family size, and, at postmenopausal ages, increasing body weight.ConclusionsIn many LMICs, the future cancer burden will be worsened by changing lifestyles. Affected common cancer sites likely to experience the largest increases are lung, colon, UADT, and breast.
Mechanism for the postive inotropic effect of angiotensin II on isolated cardiac muscle.
Authors: R J Freer, A J Pappano, M J Peach, K T Bing, M J McLean, S Vogel, N Sperelakis
Journal: Circulation Research (1976)

Angiotensin II (A II) and analogues were tested for their ability to restore electrical and mechanical activity to cardiac muscle preparations in which the fast Na+ channels had been inactivated by partial depolarization (22-27 mM K+) or by tetrodotoxin (TTX). The partially depolarized or TTX-blocked preparations were chosen because under these conditions electrical and mechanical responses are primarily Ca2+ -dependent. In depolarized rabbit right atria, A II restored spontaneous mechanical and electrical activity (measured by both intracellular and extracellular recording techniques). The frequency of action potential discharge was concentration-dependent; the threshold concentration of A II was 10(-10) M, the ED50 was 8 X 10(-9) M, and the maximum effect was observed at 5 X 10(-8) M. In contrast, depolarized guinea pig atria were insensitive to A II, Sar1-angiotensin II, and des-Asp1-angiotensin II, even at concentrations as high as 10(-5) M. Rabbit papillary muscle (TTX-blocked), embryonic (18-day) chick heart (partially depolarized) and chick heart reaggregates (TTX-blocked) responded similarly to rabbit atria in that A II (9.6 X 10(-7) M) restored both electrical and mechanical activity. We found that in these preparations the action of A II was unaffected by propranolol (5.0 X 10(-6) M to 5.0 X 10(-5) M) but was blocked by Mn2+ (10(-3) M), D-600 (1 X 10(-7) g/ml) and the specific A II antagonists Sar1-Ala8-angiotensin II (P-113) (5.0 X 10(-5) M) and Sar1-Ile8-angiotensin II (5.28 X 10(-5) M). We conclude that the positive inotropic effect of A II on the myocardium is due to its ability to increase transmembrane ion movements in or through the cell membrane. The ability of Mn2+ and D-600 to block this effect suggests that this ion movement is via the so-called "slow channels."
Plasminogen activator-specific inhibitors produced by human monocytes/macrophages.
Authors: A Wohlwend, D Belin, J D Vassalli
Journal: The Journal of Experimental Medicine (1987)

Human monocytes/macrophages produce plasminogen activator-specific inhibitors (PAIs) that form covalent complexes with urokinase-type plasminogen activator (uPA). We have characterized two functionally and antigenically related forms of PAIs produced by resting and phorbol myristate acetate (PMA)-treated U 937 cells: an Mr 40,000 form, presumably nonglycosylated, with a pI of 5.2, that is constitutively synthetized by these cells and that remains predominantly intracellular; a PMA-induced form of heterogeneous Mr (50,000-65,000) with a pI of 4.7, that is preferentially secreted; this PAI is glycosylated with terminal sialic acid residue(s). Biosynthetic labeling experiments demonstrated that both PAIs are synthetized by U 937 cells. They are inactivated upon treatment with propanol, heat, and acid; the covalent and equimolar complexes formed between these PAIs and 125I-uPA are dissociated by ammonium hydroxide, suggesting that the PAIs are linked to uPA via an ester bond. Human peripheral blood monocytes/macrophages also produce the two forms of PAI. These PAIs are clearly different from the main plasma protease inhibitors and they are both antigenically related to the PAI-2 characterized in human placenta.