tbuckley/cabot-search huggingface dataset:
P17.01 * CHROMOSOME ARM 9P LOSS OF HETEROZYGOSITY IS A MARKER OF SHORTER SURVIVAL IN 1P/19Q CO-DELETED ANAPLASTIC OLIGODENDROGLIOMA. A POLA NETWORK STUDY
Authors: A. Alentorn, C. Dehais, C. Carpentier, K. Mokhtari, F. Ducray, D. Figarella-Branger, J. Delattre, A. Idbaih, P. N. P. e. c. d. O. A. (POLA)"
Journal: Neuro-Oncology (2014)

Anaplastic or WHO grade III oligodendrogliomas (AO) are a heterogeneous subgroup of diffuse glial tumors in adults. Three major histomolecular subtypes with clinical relevance have been individualized: (i) 1p/19q co-deleted AO -80% of cases-, (ii) non 1p/19q co-deleted and IDH mutated AO -10% of cases- and (iii) non 1p/19q co-deleted and IDH wild-typeAO -10% of cases-. 1p/19q co-deleted AO, and to a lesser extent IDH mutated AO, have better prognosis and better response to treatment with a median survival of more than 10 years, as shown in two phase III international trials. We have recently shown that loss of heterozygosity (LOH) in chromosome arm 9p, with copy number loss -CL LOH- or without -Copy Neutral LOH- is a frequent event in AO. Interestingly, 9p CN LOH, inducing gene under-expression, has biological significance. In the present study, we address the prognostic value of 9p loss in 1p/19q co-deleted AO. In the present study, 228 AO exhibiting 1p/19q co-deletion were included. All tumors were centrally reviewed in the setting of the French national network for high-grade oligodendroglial tumors (POLA network) that recruits prospectively newly diagnosed anaplastic oligodendroglial tumors. Tumor DNA was analyzed using high-resolution single nucleotide polymorphism array analysis. In the entire series, 70/228 (1/3) harbored 9p loss including CN-LOH, homozygous loss or CL-LOH. 9p loss was associated with a worse prognosis in 1p19q co-deleted AO in univariate analysis (3-years OS of 98% vs. 74%, p < 0.001) whereas PFS at three years was not significantly different (3-years PFS of 88% vs. 66% p = 0.1). After adjustment for age, KPS, and treatment, multivariate analysis demonstrated 9p loss to be an independent prognostic factor for OS, p-value = 0.03, HR = 4.9 [1.2-16], but not for PFS. 1p19q co-deleted AO harboring 9p loss have shorter overall survival compared to their non 9p-lost counterparts in this prospective cohort. Further studies are needed to validate our findings.
Cartilage of the patella. Topographical variation of glycosaminoglycan content in normal and fibrillated tissue.
Authors: C Ficat, A Maroudas
Journal: Annals of the Rheumatic Diseases (1975)

The variation in the glycosaminoglycan content was studied at different sites of the patella, both where the cartilage was intact and where it showed varying degrees of fibrillation. It was found that when the cartilage surface was intact the glycosaminoglycan content was the same at the different sites of the patella. Local fibrillation always gave rise to a local lowering of fixed charge density, the magnitude of the latter correlating well with the visual assessment of the severity of the lesion. Even in the presence of severe lesions, if there was a site left on the patella where the cartilage was visually normal, its fixed charge density was also at a normal level. Thus, the depletion of glycosaminoglycans is a local phenomenon, limited to the area of fibrillation. The glycosaminoglycan content of normal cartilage is lower in the knee joint than in the hip. This fact, together with the existence of high pressure during load bearing, may be responsible for the greater frequency of destructive lesions affecting the cartilage of the patella compared with that of the hip.
Life-threatening allergic bronchopulomnary aspergillosis treated with methylprednisolone and anti-IgE monoclonal antibody
Authors: Matthew F Thomas
Journal: Journal of the Royal Society of Medicine (2009)

Allergic bronchopulmonary aspergillosis (ABPA) is a recognized disorder in patients with cystic fibrosis. It is characterized clinically by wheeze, productive cough and pulmonary infiltrates associated with a decline in lung function. The diagnosis is classically made using a combination of clinical, immunological and microbiological criteria. The most commonly used treatment is at present corticosteroids, with their attendant side-effects. The case described illustrates some of the pitfalls in making the diagnosis and outlines the use of two potential emerging therapies in the form of intravenous Methylprednisolone and the recombinant anti-IgE monoclonal antibody Omalizumab.
Atypical femur fractures associated with use of bisphosphonates and denosumab
Authors: A. Farooki, M. Fornier, P. Boland
Journal: Annals of Oncology (2015)

As a comment on the ESMO 2014 bone and cancer guidelines, this letter highlights atypical femur fracture as a rare but serious adverse effect of bisphosphonates and denosumab.
Topical 0.5% Ivermectin Lotion for Treatment of Head Lice
Authors: David M. Pariser, Terri Lynn Meinking, Margie Bell, William G. Ryan
Journal: New England Journal of Medicine (2012)

The emergence of resistance to treatment complicates the public health problem of head-louse infestations and drives the need for continuing development of new treatments. There are limited data on the activity of ivermectin as a topical lousicide.
ACCESS EUROPE: A POST MARKET STUDY OF THE MITRACLIP SYSTEM FOR THE TREATMENT OF SIGNIFICANT MITRAL REGURGITATION (MR) IN EUROPE: ANALYSIS OF OUTCOMES AT 6-MONTHS
Authors: Francesco Maisano, Olaf Franzen, Stephan Baldus, Joerg Hausleiter, Christian Butter, Ulrich Schafer, Giovanni Pedrazzini, Gian Paolo Ussia, Horst Sievert, Lars Soendergaard, Wolfgang Schillinger
Journal: Journal of the American College of Cardiology (2012)
Abstract 3912: The role of autophagy in prostate tumorigenesis and its therapeutic implications
Authors: Marco A. De Velasco, Yurie Kura, Naomi Ando, Emiko Fukushima, Yuji Hatanaka, Yutaka Yamamoto, Nobutaka Shimizu, Kazuhiro Yoshimura, Masahiro Nozawa, Kazuhiro Yoshikawa, Kazuto Nishio, Hirotsugu Uemura
Journal: Cancer Research (2014)

Abstract Autophagy is a self-catabolic process that maintains intracellular homeostasis and prolongs cell survival during metabolic stress. Increasing evidence also suggests that autophagy is induced during therapeutic stress and is believed to promote drug resistance limiting the treatment efficacy of anticancer drugs. Our goal was to define the role of autophagy during prostate cancer tumorigenesis and determine the consequences of pharmacological intervention. We used a genetically engineered mouse model of prostate cancer that is based on the PSA-Cre driven inactivation of PTEN to show that autophagy is induced during tumor progression and the transformation to castration resistant prostate cancer. We also report that inhibition of autophagy by the conditional inactivation of ATG7, a gene essential for autophagosome formation, does not contribute to initiate prostate cancer. However, simultaneous inactivation of ATG7 and PTEN leads to suppressed tumor progression in castration-naïve and CRPC models. Additionally PTEN/ATG7 double gene knockout mice were more sensitive to targeted mTOR inhibition than PTEN single gene knockouts. Pharmacological inhibition of autophagy using the lysomotropic agent chloroquine synergized with everolimus to inhibit survival of human and mouse prostate cancer cells in vitro. Despite a strong antitumor activity in vitro, the combinations of everolimus and chloroquine failed to demonstrate any meaningful improvement over everolimus alone when tested in vivo with PTEN-mutant mice. In summary, our findings demonstrate that autophagy is required for prostate cancer progression and contributes to therapeutic resistance; however, pharmacological inhibition of autophagy, using a lysomotropic agent, was ineffective in producing a meaningful antitumor benefit in an autochthonous cancer system. Our preliminary findings suggest a need for further investigation before implementing the concept of autophagy inhibition into clinical trials. Citation Format: Marco A. De Velasco, Yurie Kura, Naomi Ando, Emiko Fukushima, Yuji Hatanaka, Yutaka Yamamoto, Nobutaka Shimizu, Kazuhiro Yoshimura, Masahiro Nozawa, Kazuhiro Yoshikawa, Kazuto Nishio, Hirotsugu Uemura. The role of autophagy in prostate tumorigenesis and its therapeutic implications. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3912. doi:10.1158/1538-7445.AM2014-3912
The “Pill-in-the-Pocket” Approach to Atrial Fibrillation
Authors: Ann K Wittkowsky
Journal: New England Journal of Medicine (2005)

to the editor: Alboni and colleagues (Dec. 2 issue) 1 present data from a prospective study investigating the strategy of rhythm control in patients with paroxysmal atrial fibrillation by self-administration of antiarrhythmic agents (the “pill-in-thepocket” approach). According to the inclusion criteria, patients 18 to 75 years old were recruited, with 44 percent of the study population having some structural heart disease. Therefore, some of these patients were likely to have had risk factors for stroke and should have received antithrombotic therapy, which is considered a cornerstone of treatment for atrial fibrillation. 2-4 Accordingly, the authors should provide additional information on the short-term and long-term anticoagulation regimens and on the outcome with regard to transient ischemia, stroke, or arterial embolism in their patients.
67 MOLECULAR CHARACTERIZATION OF HCV RESISTANCE TO TELAPREVIR BY MEANS OF ULTRA-DEEP PYROSEQUENCING: PREEXISTING RESISTANT VARIANTS AND DYNAMICS OF RESISTANT POPULATIONS
Authors: S. Chevaliez, C. Rodriguez, A. Soulier, A. Ahmed-Belkacem, C. Hèzode, J.-M. Pawlotsky
Journal: Journal of Hepatology (2011)
Cytoplasmic nucleophosmin in myeloid sarcoma occurring 20 years after diagnosis of acute myeloid leukaemia
Authors: Niccolò Bolli, Sara Galimberti, Maria P Martelli, Alessia Tabarrini, Giovanni Roti, Cristina Mecucci, Massimo F Martelli, Mario Petrini, Brunangelo Falini
Journal: The Lancet Oncology (2006)
ATP regulation of the slow calcium channels in vascular smooth muscle cells of guinea pig mesenteric artery.
Authors: Y Ohya, N Sperelakis
Journal: Circulation Research (1989)

Effects of intracellularly perfused ATP, and extracellularly applied cyanide and 2-deoxy-D-glucose, on fast and slow Ca2+ channel currents of isolated single vascular smooth muscle cells were investigated by a whole-cell voltage-clamp method combined with an intracellular perfusion technique. Single smooth muscle cells were prepared by collagenase treatment from guinea pig small mesenteric arteries (diameter of less than 300 micron). With Cs+-rich solution in the pipette and isotonic Ba2+ solution (100 mM) in the bath, depolarizing pulses evoked two types of the Ca2+ channel current. Depolarizing pulses from the holding potential of -80 mV to over -30 mV evoked a fast Ca2+ channel current. This fast component was inhibited by shifting the holding potential in a positive direction. With a holding potential of -40 mV, the fast component was almost inhibited. In contrast, the slow current was evoked by command potentials to above -10 mV, and its full amplitude was preserved at the holding potential of -40 mV. Without ATP in the pipette, the fast current was dominant. Increase in the ATP concentration in the pipette (0.3 to 5 mM) enhanced the slow current but did not affect the fast current. Maximum enhancement of the slow current was observed at 5 mM ATP. Increase in ATP concentration, however, did not modify the shape of the current trace and the steady state inactivation curve of the slow current. Maximum amplitudes of the fast current and slow current recorded with 5 mM ATP averaged 17.4 pA (SD of 10.4 pA, n = 30; observed at -10 mV to +10 mV) and 141.8 pA (SD of 27.1 pA, n = 30; observed at +30 mV to +40 mV), respectively. Presence of CN- and 2-deoxy-D-glucose (without glucose) in the bath, and absence of ATP in the pipette, abolished the slow current within 10 minutes; in contrast, it took more than 10 minutes to depress the fast current. The inhibitory effect of CN- and 2-deoxy-D-glucose on the slow current was reduced by intracellular application of ATP. In summary, the activation of the slow Ca2+ channel required physiological concentration of ATP, whereas the fast channel current was preserved, even under ATP-free conditions. These results indicate that only the slow current is a metabolically dependent Ca2+ channel current in these vascular smooth muscle cells.
Increased humoral immunity in the jejunum of diarrhoea-predominant irritable bowel syndrome associated with clinical manifestations
Authors: Maria Vicario, Ana M González-Castro, Cristina Martínez, Beatriz Lobo, Marc Pigrau, Mar Guilarte, Inés de Torres, Jose L Mosquera, Marina Fortea, César Sevillano-Aguilera, Eloisa Salvo-Romero, Carmen Alonso, Bruno K Rodiño-Janeiro, Johan D Söderholm, Fernando Azpiroz, Javier Santos
Journal: Gut (2014)

<h3>Background and aims</h3> Altered intestinal barrier is associated with immune activation and clinical symptoms in diarrhoea-predominant IBS (IBS-D). Increased mucosal antigen load may induce specific responses; however, local antibody production and its contribution to IBS aetiopathogenesis remain undefined. This study evaluated the role of humoral activity in IBS-D. <h3>Methods</h3> A single mucosal jejunal biopsy, luminal content and blood were obtained from healthy volunteers (H; n=30) and IBS-D (n=49; Rome III criteria) participants. Intraepithelial lymphocytes, mast cells, B lymphocytes and plasma cells were studied by imaging techniques. Differential gene expression and pathway analysis were assessed by microarray and PCR techniques. Blood and luminal immunoglobulins (Igs) were quantified. Gastrointestinal symptoms, respiratory atopy and stress and depression were also recorded. <h3>Results</h3> Patients with IBS-D showed a higher number and activation of mucosal B lymphocytes and plasma cells (p&lt;0.05). Mast cell density was increased in patients with IBS-D (non-atopic) and in close proximity to plasma cells (p&lt;0.05). Microarray profiling identified differential humoral activity in IBS-D, involving proliferation and activation of B lymphocytes and Igs production (p&lt;0.001). Mucosal humoral activity was higher in IBS-D, with upregulation of germline transcripts and Ig genes (1.3-fold–1.7-fold increase; p&lt;0.05), and increased IgG<sup>+</sup> cells and luminal IgG compared with H (p&lt;0.05), with no differences in blood. Biological markers of humoral activity correlated positively with bowel movements, stool form and depression. <h3>Conclusions</h3> Enhanced small bowel humoral immunity is a distinctive feature of IBS-D. Mucosal Ig production contributes to local inflammation and clinical manifestations in IBS-D.
99mTc-Labelled serum albumin in cardiac output and blood volume studies
Authors: M. J. Williams, T. Deegan
Journal: Thorax (1971)

The use of human serum albumin labelled with iodine-131 (RIHSA) as the radioactive indicator in the measurement of cardiac output by the external counting technique is not ideal since the emission characteristics, physical half-life, and physiological fate restrict the amount that can be administered. A more suitable material, especially because of the short physical half-life of the isotope involved, is albumin labelled with technetium-99m. This communication describes a simple three-stage process for the preparation of such a complex which was then tested in subjects with no impairment of cardiac performance for its suitability in assays of cardiac output by the external counting method. Values were within the same range as those obtained with RIHSA in comparable subjects. Blood volumes estimated with <sup>99m</sup>Tc-albumin were within the limits of physiological variation of values derived with RIHSA in the same subjects. Serial blood samplings and urine collection during a period of 24 hours after administration showed that the preparation was lost continuously from the circulation at a more rapid rate than RIHSA. The greatest loss was in the first few hours when most of the urinary excretion of the isotope occurred. Comparison of the present data with published results using an alternative preparation suggests that our product may be more stable.
The potential use of expression profiling: implications for predicting treatment response in rheumatoid arthritis
Authors: Samantha Louise Smith, Darren Plant, Stephen Eyre, Anne Barton
Journal: Annals of the Rheumatic Diseases (2013)

Whole genome expression profiling, or transcriptomics, is a high throughput technology with the potential for major impacts in both clinical settings and drug discovery and diagnostics. In particular, there is much interest in this technique as a mechanism for predicting treatment response. Gene expression profiling entails the quantitative measurement of messenger RNA levels for thousands of genes simultaneously with the inherent possibility of identifying biomarkers of response to a particular therapy or by singling out those at risk of serious adverse events. This technology should contribute to the era of stratified medicine, in which patient specific populations are matched to potentially beneficial drugs via clinical tests. Indeed, in the oncology field, gene expression testing is already recommended to allow rational use of therapies to treat breast cancer. However, there are still many issues surrounding the use of the various testing platforms available and the statistical analysis associated with the interpretation of results generated. This review will discuss the implications this promising technology has in predicting treatment response and outline the various advantages and pitfalls associated with its use.
Prophylactic Cranial Irradiation for Patients With Small-Cell Lung Cancer in Complete Remission
Authors: R. Arriagada, T. Le Chevalier, F. Borie, A. Riviere, P. Chomy, I. Monnet, A. Tardivon, F. Viader, M. Tarayre, S. Benhamou
Journal: JNCI Journal of the National Cancer Institute (1995)

Background : Prophylactic cranial irradiation in patients with small-cell lung cancer decreases the overall rate of brain metastases without an effect on overall survival. It has been suggested that this treatment may increase neuro-psychological syndromes and brain abnormalities indicated by computed tomography scans. However, other retrospective data suggested a beneficial effect on overall survival for patients in complete remission. Purpose : Our purpose was to evaluate the effects of prophylactic cranial irradiation on brain metastasis, overall survival, and late-occurring toxic effects in patients with small-cell lung cancer in complete remission. Methods : We conducted a prospective study of 300 patients who had small-cell lung cancer that was in complete remission. The patients were randomly assigned to receive either prophylactic cranial irradiation delivering 24 Gy in eight fractions during 12 days (treatment group) or no prophylactic cranial irradiation (control group). A neuro-psychological examination and a computed tomography scan of the brain were performed at the time of random assignment and repeatedly assessed at 6, 18, 30, and 48 months. Patterns of failure were analyzed according to total event rates and also according to an isolated first site of relapse, using a competing-risk approach. Results : Two hundred ninety-four patients who did not have brain metastases at the time of random assignment were analyzed. The 2-year cumulative rate of brain metastasis as an isolated first site of relapse was 45% in the control group and 19% in the treatment group ( P <10 −6 ). The total 2-year rate of brain metastasis was 67% and 40%, respectively (relative risk = 035; P <10 −13 ). The 2-year overall survival rate was 21.5% in the control group and 29% in the treatment group (relative risk = 0.83; P =.14). There were no significant differences between the two groups in terms of neuropsychological function or abnormalities indicated by computed tomography brain scans. Conclusions: Prophylactic cranial irradiation given to patients with small-cell lung cancer in complete remission decreases the risk of brain metastasis threefold without a significant increase in complications. A possible beneficial effect on overall survival should be tested with a higher statistical power. Implications : The results of the trial favor, at present, the indication of prophylactic cranial irradiation for patients who are in complete remission. A longer follow-up and confirmatory trials are needed to fully assess late-occurring toxic effects. The possible effect on overall survival needs to be evaluated with a larger number of patients in complete remission, and a meta-analysis of similar trials is recommended. [J Natl Cancer Inst 87: 183–190, 1995]
A Monoclonal Antibody Against α <sub>V</sub> β <sub>3</sub> Integrin Inhibits Development of Atherosclerotic Lesions in Diabetic Pigs
Authors: Laura A. Maile, Walker H. Busby, Timothy C. Nichols, Dwight A. Bellinger, Elizabeth P. Merricks, Michael Rowland, Umadevi Veluvolu, David R. Clemmons
Journal: Science Translational Medicine (2010)

An antibody directed at the C terminus of an integrin subunit can prevent the formation of atherosclerotic lesions in diabetic pigs.
The Development of B Cells in the Bone Marrow Is Controlled by the Balance between Cell-Autonomous Mechanisms and Signals from the Microenvironment
Authors: Rita Carsetti
Journal: The Journal of Experimental Medicine (2000)

B cells are generated from hematopoietic stem cells (HSCs) in the liver during the fetal life, and in the bone marrow in the adult. The differentiation pathway from HSC to mature B cell can be divided into several stages, based on the phenotype and on functional properties that cells of the B
Statistical assessment of the global regulatory role of histone acetylation in Saccharomyces cerevisiae.
Authors: Guo-Cheng Yuan, Ping Ma, Wenxuan Zhong, Jun S Liu
Journal: Genome biology (2006)

Abstract Background Histone acetylation plays important but incompletely understood roles in gene regulation. A comprehensive understanding of the regulatory role of histone acetylation is difficult because many different histone acetylation patterns exist and their effects are confounded by other factors, such as the transcription factor binding sequence motif information and nucleosome occupancy. Results We analyzed recent genomewide histone acetylation data using a few complementary statistical models and tested the validity of a cumulative model in approximating the global regulatory effect of histone acetylation. Confounding effects due to transcription factor binding sequence information were estimated by using two independent motif-based algorithms followed by a variable selection method. We found that the sequence information has a significant role in regulating transcription, and we also found a clear additional histone acetylation effect. Our model fits well with observed genome-wide data. Strikingly, including more complicated combinatorial effects does not improve the model's performance. Through a statistical analysis of conditional independence, we found that H4 acetylation may not have significant direct impact on global gene expression. Conclusion Decoding the combinatorial complexity of histone modification requires not only new data but also new methods to analyze the data. Our statistical analysis confirms that histone acetylation has a significant effect on gene transcription rates in addition to that attributable to upstream sequence motifs. Our analysis also suggests that a cumulative effect model for global histone acetylation is justified, although a more complex histone code may be important at specific gene loci. We also found that the regulatory roles among different histone acetylation sites have important differences.