tbuckley/cabot-search huggingface dataset:
In patients with early rheumatoid arthritis, the new ACR/EULAR definition of remission identifies patients with persistent absence of functional disability and suppression of ultrasonographic synovitis
Authors: Garifallia Sakellariou, Carlo Alberto Scirè, Suzanne M M Verstappen, Carlomaurizio Montecucco, Roberto Caporali
Journal: Annals of the Rheumatic Diseases (2012)

To test the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) and disease activity score in 44 and 28 joints (DAS, DAS28) definitions of remission in early rheumatoid arthritis (RA), against disability and ultrasound-detectable synovitis.In an observational study of early RA patients, remission rates were determined and compared in 166 patients. The remission definitions included the simplified disease activity index (SDAI≤3.3), ACR/EULAR (categorical), DAS28 (<2.6) and DAS (<1.6). The health assessment questionnaire (HAQ) was completed at baseline and 12 months, power Doppler-positive synovitis (PDPS) was assessed at baseline, 6 and 12 months. Cross-sectionally, the outcomes were low functional disability (HAQ≤0.5) or absent PDPS in all joints, while longitudinally the outcomes were stable low functional disability and persistent absent PDPS in all joints.At baseline, 33.7% of patients achieved DAS28 remission, 43.37% DAS remission, 16.8% SDAI remission, 13.8% ACR/EULAR remission. DAS28, SDAI and ACR/EULAR remission was cross-sectionally associated with low functional disability and absent PDPS. All definitions were longitudinally associated with low functional disability: positive likelihood ratios (LR+) of 3.24 for DAS28, 2.14 for DAS, 4.86 for SDAI, 5.67 for ACR/EULAR criteria, and with absent PDPS for DAS28 (LR+ 1.66), SDAI (LR+ 6.46), ACR/EULAR (LR+ 5.07).The new remission definitions confirmed their validity in an observational setting and identify patients with better disease control.
Case of Prolonged Bradycardia Induced by Bevacizumab-Associated Infusion Reaction in Advanced Metastatic Colon Cancer
Authors: Y. Mori, S.-e. Kudo, K. Wakamura, S. Matsudaira, M. Misawa, Y. Sugihara, Y. Koyama, K.-i. Takeda, T. Kudo, H. Miyachi
Journal: Annals of Oncology (2013)
Stem Cell Emergence and Hemopoietic Activity Are Incompatible in Mouse Intraembryonic Sites
Authors: Isabelle Godin, Juan Antonio Garcia-Porrero, Françoise Dieterlen-Lièvre, Ana Cumano
Journal: The Journal of Experimental Medicine (1999)

In the mouse embryo, the generation of candidate progenitors for long-lasting hemopoiesis has been reported in the paraaortic splanchnopleura (P-Sp)/ aorta-gonad-mesonephros (AGM) region. Here, we address the following question: can the P-Sp/AGM environment support hemopoietic differentiation as well as generate stem cells, and, conversely, are other sites where hemopoietic differentiation occurs capable of generating stem cells? Although P-Sp/AGM generates de novo hemopoietic stem cells between 9.5 and 12.5 days post coitus (dpc), we show here that it does not support hemopoietic differentiation. Among mesoderm-derived sites, spleen and omentum were shown to be colonized by exogenous cells in the same fashion as the fetal liver. Cells colonizing the spleen were multipotent and pursued their evolution to committed progenitors in this organ. In contrast, the omentum, which was colonized by lymphoid-committed progenitors that did not expand, cannot be considered as a hemopoietic organ. From these data, stem cell generation appears incompatible with hemopoietic activity. At the peak of hemopoietic progenitor production in the P-Sp/AGM, between 10.5 and 11.5 dpc, multipotent cells were found at the exceptional frequency of 1 out of 12 total cells and 1 out of 4 AA4.1+ cells. Thus, progenitors within this region constitute a pool of undifferentiated hemopoietic cells readily accessible for characterization.
Potassium Channel KCNA1 Modulates Oncogene-Induced Senescence and Transformation
Authors: Hélène Lallet-Daher, Clotilde Wiel, Delphine Gitenay, Naveenan Navaratnam, Arnaud Augert, Benjamin Le Calvé, Stéphanie Verbeke, David Carling, Sébastien Aubert, David Vindrieux, David Bernard
Journal: Cancer Research (2013)

Oncogene-induced senescence (OIS) constitutes a failsafe program that restricts tumor development. However, the mechanisms that link oncogenesis to senescence are not completely understood. We carried out a loss-of-function genetic screen that identified the potassium channel KCNA1 as a determinant of OIS escape that can license tumor growth. Oncogenic stress triggers an increase in KCNA1 expression and its relocation from the cytoplasm to the membrane. Mechanistically, this relocation is due to a loss of protein kinase A (PKA)-induced phosphorylation at residue S446 of KCNA1. Accordingly, sustaining PKA activity or expressing a KCNA1 phosphomimetic mutant maintained KCNA1 in the cytoplasm and caused escape from OIS. KCNA1 relocation to the membrane induced a change in membrane potential that invariably resulted in cellular senescence. Restoring KCNA1 expression in transformation-competent cells triggered variation in membrane potential and blocked RAS-induced transformation, and PKA activation suppressed both effects. Furthermore, KCNA1 expression was reduced in human cancers, and this decrease correlated with an increase in breast cancer aggressiveness. Taken together, our results identify a novel pathway that restricts oncogenesis through a potassium channel-dependent senescence pathway.
Sleep-related laryngospasm
Authors: R Thurnheer, S Henz, A Knoblauch
Journal: European Respiratory Journal (1997)

The term "sleep-related laryngospasm" refers to episodic, abrupt interruption of sleep accompanied by feelings of acute suffocation followed by stridor. The condition is included in the diagnostic and coding manual of the American Sleep Disorders Association (ASDA), but there are few references in the peer-reviewed literature. Our description of the distinct clinical picture associated with this condition is based on an analysis of the histories of a series of 10 patients. The patients and their families gave precise, uniform accounts of the dramatic attacks. Diagnostic work-up included pulmonary and gastroenterological assessment. All patients reported sudden awakening from sleep due to feelings of acute suffocation, accompanied by intense fear. Apnoea lasting 5-45 s was followed by stridor. Breathing returned to normal within minutes. Patients were left exhausted by the attacks. Nine of our 10 patients had evidence of gastro-oesophageal reflux and six responded to antireflux therapy. We conclude that the nocturnal choking attacks (and the occasional daytime attacks experienced by some of the patients) are caused by laryngospasm. The pathogenesis of the apparent underlying laryngeal irritability is unknown. The condition may be related to a gastro-oesophageal reflux.
Lentivector-mediated RNAi efficiently suppresses prion protein and prolongs survival of scrapie-infected mice
Authors: Alexander Pfeifer, Sabina Eigenbrod, Saba Al-Khadra, Andreas Hofmann, Gerda Mitteregger, Markus Moser, Uwe Bertsch, Hans Kretzschmar
Journal: Journal of Clinical Investigation (2006)

Prion diseases are fatal neurodegenerative diseases characterized by the accumulation of PrPSc, the infectious and protease-resistant form of the cellular prion protein (PrPC). We generated lentivectors expressing PrPC-specific short hairpin RNAs (shRNAs) that efficiently silenced expression of the prion protein gene (Prnp) in primary neuronal cells. Treatment of scrapie-infected neuronal cells with these lentivectors resulted in an efficient and stable suppression of PrPSc accumulation. After intracranial injection, lentiviral shRNA reduced PrPC expression in transgenic mice carrying multiple copies of Prnp. To test the therapeutic potential of lentiviral shRNA, we used what we believe to be a novel approach in which the clinical situation was mimicked. We generated chimeric mice derived from lentivector-transduced embryonic stem cells. Depending on the degree of chimerism, these animals carried the lentiviral shRNAs in a certain percentage of brain cells and expressed reduced levels of PrPC. Importantly, in highly chimeric mice, survival after scrapie infection was significantly extended. Taken together, these data suggest that lentivector-mediated RNA interference could be an approach for the treatment of prion disease.
Endothelial Dysfunction: Associations with Exposure to Ambient Fine Particles in Diabetic Individuals
Authors: Alexandra Schneider, Lucas Neas, Margaret C. Herbst, Martin Case, Ronald W. Williams, Wayne Cascio, Alan Hinderliter, Fernando Holguin, John B. Buse, Kathleen Dungan, Maya Styner, Annette Peters, Robert B. Devlin
Journal: Environmental Health Perspectives (2008)

Exposure to fine airborne particulate matter [< or =2.5 microm in aerodynamic diameter (PM(2.5))] has been associated with cardiovascular and hematologic effects, especially in older people with cardiovascular disease. Some epidemiologic studies suggest that adults with diabetes also may be a particularly susceptible population.The purpose of this study was to analyze the short-term effects of ambient PM(2.5) on markers of endothelial function in diabetic volunteers.We conducted a prospective panel study in 22 people with type 2 diabetes mellitus in Chapel Hill, North Carolina (USA), from November 2004 to December 2005. We acquired daily measurements of PM(2.5) and meteorologic data at central monitoring sites. On 4 consecutive days, we measured endothelial function by brachial artery ultrasound in all participants and by pulsewave measurements in a subgroup. Data were analyzed using additive mixed models with a random participant effect and adjusted for season, day of the week, and meteorology.Flow-mediated dilatation decreased in association with PM(2.5) during the first 24 hr, whereas small-artery elasticity index decreased with a delay of 1 and 3 days. These PM(2.5)-associated decrements in endothelial function were greater among participants with a high body mass index, high glycosylated hemoglobin A1c, low adiponectin, or the null polymorphism of glutathione S-transferase M1. However, high levels of myeloperoxidase on the examination day led to strongest effects on endothelial dysfunction.These data demonstrate that PM(2.5) exposure may cause immediate endothelial dysfunction. Clinical characteristics associated with insulin resistance were associated with enhanced effects of PM on endothelial function. In addition, participants with greater oxidative potential seem to be more susceptible.
Survival in small cell lung carcinoma after surgery.
Authors: H R Sorensen, C Lund, P Alstrup
Journal: Thorax (1986)

In a retrospective study of long term survival in patients with small cell carcinoma of the lung who had been treated purely by surgery, 1820 patients with lung cancer seen during the 15 years 1962-77 were reviewed and reclassified histologically and according to the TNM system. Of these patients, 924 had had resections and 284 exploratory thoracotomies. Cancer chemotherapy was not used in this period and radiotherapy was given only occasionally as palliative treatment. Seventy seven of the patients having pulmonary resections had small cell carcinoma (8.4%), and there were six survivors among the 71 with T1-2, N0-1, M0 tumours. The five and 10 year survival rates were both 12%. The histological specimens from these six patients with a small cell carcinoma who survived more than 10 years were re-evaluated and confirmed as small cell by an independent group of pathologists. It seems justified to conclude that a selected group of patients with small cell carcinoma should be treated by surgery alone without adjuvant chemotherapy, which might reduce the long term survival.
Distinct p53 Gene Signatures Are Needed to Predict Prognosis and Response to Chemotherapy in ER-Positive and ER-Negative Breast Cancers
Authors: Charles Coutant, Roman Rouzier, Yuan Qi, Jacqueline Lehmann-Che, Giampaolo Bianchini, Takayuki Iwamoto, Gabriel N. Hortobagyi, W. Fraser Symmans, Serge Uzan, Fabrice Andre, Hugues de Thé, Lajos Pusztai
Journal: Clinical Cancer Research (2011)

Estrogen receptor-positive (ER+) and -negative (ER) breast cancers are molecularly distinct diseases. We hypothesized that p53 mutations may lead to different transcriptional changes and carry different prognostic value in these two different types of cancers.We developed a 39-gene p53 signature derived from 213 ER+ and a separate 30-gene signature from 38 ER- cancers with known mutation status and tested their prognostic and chemotherapy response predictive values in ER+ and ER- cancers, respectively.External validation to predict p53 status (n = 103) showed sensitivity and specificity of 89% and 54% for the 39-gene signature, and 82% and 61% for the 30-gene signature. The 39-gene signature was predictive of worse distant metastasis free survival in ER+ cancers in two separate prognostic data sets (n = 255, HR: 2.3, P = 0.005 and n = 198, HR: 2.17, P = 0.09). It also predicted for poor prognosis even with adjuvant tamoxifen therapy (n = 277, HR = 2.43, P < 0.0001) but it was not prognostic in ER- cancers. It was also associated with higher chemotherapy sensitivity in ER+ but not in ER- cancers. The prognostic and predictive values remained significant in multivariate analysis. The 30-gene, ER-, p53 signature showed no prognostic or predictive values in ER+ cancers but it was associated with better prognosis in ER- cancers. It also had no chemotherapy response predictive value in ER- or ER+ cancers.P53 dysfunction is prognostically most relevant in ER+ cancers and supports the hypothesis that different predictive or prognostic markers will be needed for different molecular subsets of breast cancer.
Inhibition of NF-κB by a TAT-NEMO–binding domain peptide accelerates constitutive apoptosis and abrogates LPS-delayed neutrophil apoptosis
Authors: Mira Choi, Susanne Rolle, Maren Wellner, M. Cristina Cardoso, Claus Scheidereit, Friedrich C. Luft, Ralph Kettritz
Journal: Blood (2003)
Oxaliplatin Combined With Weekly Bolus Fluorouracil and Leucovorin As Surgical Adjuvant Chemotherapy for Stage II and III Colon Cancer: Results From NSABP C-07
Authors: J. Philip Kuebler, H. Samuel Wieand, Michael J. O'Connell, Roy E. Smith, Linda H. Colangelo, Greg Yothers, Nicholas J. Petrelli, Michael P. Findlay, Thomas E. Seay, James N. Atkins, John L. Zapas, J. Wendall Goodwin, Louis Fehrenbacher, Ramesh K. Ramanathan, Barbara A. Conley, Patrick J. Flynn, Gamini Soori, Lauren K. Colman, Edward A. Levine, Keith S. Lanier, Norman Wolmark
Journal: Journal of Clinical Oncology (2007)

This phase III clinical trial evaluated the impact on disease-free survival (DFS) of adding oxaliplatin to bolus weekly fluorouracil (FU) combined with leucovorin as surgical adjuvant therapy for stage II and III colon cancer.Patients who had undergone a potentially curative resection were randomly assigned to either FU 500 mg/m2 intravenous (IV) bolus weekly for 6 weeks plus leucovorin 500 mg/m2 IV weekly for 6 weeks during each 8-week cycle for three cycles (FULV), or the same FULV regimen with oxaliplatin 85 mg/m2 IV administered on weeks 1, 3, and 5 of each 8-week cycle for three cycles (FLOX).A total of 2,407 patients (96.6%) of the 2,492 patients randomly assigned were eligible. Median follow-up for patients still alive is 42.5 months. The hazard ratio (FLOX v FULV) is 0.80 (95% CI, 0.69 to 0.93), a 20% risk reduction in favor of FLOX (P < .004). The 3- and 4-year disease-free survival (DFS) rates were 71.8% and 67.0% for FULV and 76.1% and 73.2% for FLOX, respectively. Grade 3 neurosensory toxicity was noted in 8.2% of patients receiving FLOX and in 0.7% of those receiving FULV (P < .001). Hospitalization for diarrhea associated with bowel wall thickening occurred in 5.5% of the patients receiving FLOX and in 3.0% of the patients receiving FULV (P < .01). A total of 1.2% of patients died as a result of any cause within 60 days of receiving chemotherapy, with no significant difference between regimens.The addition of oxaliplatin to weekly FULV significantly improved DFS in patients with stage II and III colon cancer. FLOX can be recommended as an effective option in clinical practice.
Protein-protein interactions of the hyperthermophilic archaeon Pyrococcus horikoshii OT3.
Authors: Kengo Usui, Shintaro Katayama, Mutsumi Kanamori-Katayama, Chihiro Ogawa, Chikatoshi Kai, Makiko Okada, Jun Kawai, Takahiro Arakawa, Piero Carninci, Masayoshi Itoh, Koji Takio, Masashi Miyano, Satoru Kidoaki, Takehisa Matsuda, Yoshihide Hayashizaki, Harukazu Suzuki
Journal: Genome biology (2005)

Although 2,061 proteins of Pyrococcus horikoshii OT3, a hyperthermophilic archaeon, have been predicted from the recently completed genome sequence, the majority of proteins show no similarity to those from other organisms and are thus hypothetical proteins of unknown function. Because most proteins operate as parts of complexes to regulate biological processes, we systematically analyzed protein-protein interactions in Pyrococcus using the mammalian two-hybrid system to determine the function of the hypothetical proteins.We examined 960 soluble proteins from Pyrococcus and selected 107 interactions based on luciferase reporter activity, which was then evaluated using a computational approach to assess the reliability of the interactions. We also analyzed the expression of the assay samples by western blot, and a few interactions by in vitro pull-down assays. We identified 11 hetero-interactions that we considered to be located at the same operon, as observed in Helicobacter pylori. We annotated and classified proteins in the selected interactions according to their orthologous proteins. Many enzyme proteins showed self-interactions, similar to those seen in other organisms.We found 13 unannotated proteins that interacted with annotated proteins; this information is useful for predicting the functions of the hypothetical Pyrococcus proteins from the annotations of their interacting partners. Among the heterogeneous interactions, proteins were more likely to interact with proteins within the same ortholog class than with proteins of different classes. The analysis described here can provide global insights into the biological features of the protein-protein interactions in P. horikoshii.
<i>XPD</i> and <i>XRCC1</i> Genetic Polymorphisms Are Prognostic Factors in Advanced Non—Small-Cell Lung Cancer Patients Treated With Platinum Chemotherapy
Authors: Sarada Gurubhagavatula, Geoffrey Liu, Sohee Park, Wei Zhou, Li Su, John C. Wain, Thomas J. Lynch, Donna S. Neuberg, David C. Christiani
Journal: Journal of Clinical Oncology (2004)

Platinum agents cause DNA cross-linking and oxidative damage. Genetic polymorphisms of DNA repair genes are associated with differential DNA repair activity and may explain interindividual differences in overall survival after therapy with platinum agents for non-small-cell lung cancer (NSCLC).We used polymerase chain reaction-restriction fragment length polymorphism to evaluate genetic polymorphisms of the XPD (Asp312Asn) and XRCC1 (Arg399Gln) DNA repair genes in 103 patients with stage III (54%) and IV (46%) NSCLC treated with platinum-based chemotherapy.Median age was 58 years (range, 32 to 77 years), 49% were females, and there were 86 deaths. Median follow-up period was 61.9 months. Median survival time (MST) was 14.9 months; by stage, MST was 28.6 months (IIIA), 16.0 months (IIIB), and 9.3 months (IV). Genotypes were not associated with stage. Increasing numbers of either XPD or XRCC1 variant alleles were associated with shorter overall survival (P =.003 and P =.07, respectively, by log-rank test). Similarly, when we compared combinations of variant alleles across both polymorphisms, we found that a greater number of variant alleles was associated with decreasing overall survival (P =.009, log-rank test). These polymorphisms independently predicted overall survival even after taking into account stage, performance status, and chemotherapy regimen.Genetic polymorphisms in XPD and XRCC1 may be important prognostic factors in platinum-treated patients with advanced NSCLC.
The effect of microwave therapy upon muscle blood flow in man.
Authors: D. J. Wyper, D. R. McNiven
Journal: British Journal of Sports Medicine (1976)

Muscle blood flow was measured using a radioactive tracer technique in five normal subjects. Flow values obtained during application of 2450 MHz microwave therapy were compared with resting values and in each case the treatment produced a significant increase; the mean values being 2.9 ml/100g/min at rest and 11.4 ml/100g/min during application of the microwave therapy. Comparison is made with previous studies using other therapeutic agents and it is concluded that the most significant effect on muscle blood flow is produced by microwave therapy.
Patient-Derived Xenograft Models: An Emerging Platform for Translational Cancer Research
Authors: Manuel Hidalgo, Frederic Amant, Andrew V. Biankin, Eva Budinská, Annette T. Byrne, Carlos Caldas, Robert B. Clarke, Steven de Jong, Jos Jonkers, Gunhild Mari Mælandsmo, Sergio Roman-Roman, Joan Seoane, Livio Trusolino, Alberto Villanueva
Journal: Cancer Discovery (2014)

Abstract Recently, there has been an increasing interest in the development and characterization of patient-derived tumor xenograft (PDX) models for cancer research. PDX models mostly retain the principal histologic and genetic characteristics of their donor tumor and remain stable across passages. These models have been shown to be predictive of clinical outcomes and are being used for preclinical drug evaluation, biomarker identification, biologic studies, and personalized medicine strategies. This article summarizes the current state of the art in this field, including methodologic issues, available collections, practical applications, challenges and shortcomings, and future directions, and introduces a European consortium of PDX models. Significance: PDX models are increasingly used in translational cancer research. These models are useful for drug screening, biomarker development, and the preclinical evaluation of personalized medicine strategies. This review provides a timely overview of the key characteristics of PDX models and a detailed discussion of future directions in the field. Cancer Discov; 4(9); 998–1013. ©2014 AACR.