tbuckley/cabot-search huggingface dataset:
Regulation of Expression of BIK Proapoptotic Protein in Human Breast Cancer Cells: p53-Dependent Induction of BIK mRNA by Fulvestrant and Proteasomal Degradation of BIK Protein
Authors: Jingyung Hur, Daphne W. Bell, Kathleen L. Dean, Kathryn R. Coser, Pablo C. Hilario, Ross A. Okimoto, Erica M. Tobey, Shannon L. Smith, Kurt J. Isselbacher, Toshi Shioda
Journal: Cancer Research (2006)

Induction of mRNA for BIK proapoptotic protein by doxorubicin or gamma-irradiation requires the DNA-binding transcription factor activity of p53. In MCF7 cells, pure antiestrogen fulvestrant also induces BIK mRNA and apoptosis. Here, we provide evidence that, in contrast to doxorubicin or gamma-irradiation, fulvestrant induction of BIK mRNA is not a direct effect of the transcriptional activity of p53, although p53 is necessary for this induction. It is known that p53 up-regulated modulator of apoptosis (PUMA) mRNA is induced directly by the transcriptional activity of p53. Whereas gamma-irradiation induced both BIK and PUMA mRNA, only BIK mRNA was induced by fulvestrant. Whereas both fulvestrant and doxorubicin induced BIK mRNA, only doxorubicin enhanced the DNA-binding activity of p53 and induced PUMA mRNA. Small interfering RNA (siRNA) suppression of p53 expression as well as overexpression of dominant-negative p53 effectively inhibited the fulvestrant induction of BIK mRNA, protein, and apoptosis. Transcriptional activity of a 2-kb BIK promoter, which contained an incomplete p53-binding sequence, was not affected by fulvestrant when tested by reporter assay. Fulvestrant neither affected the stability of the BIK mRNA transcripts. Interestingly, other human breast cancer cells, such as ZR75-1, constitutively expressed BIK mRNA even without fulvestrant. In these cells, however, BIK protein seemed to be rapidly degraded by proteasome, and siRNA suppression of BIK in ZR75-1 cells inhibited apoptosis induced by MG132 proteasome inhibitor. These results suggest that expression of BIK in human breast cancer cells is regulated at the mRNA level by a mechanism involving a nontranscriptional activity of p53 and by proteasomal degradation of BIK protein.
Antibody to oxidized low-density lipoprotein and cardiovascular mortality in end-stage renal disease
Authors: Tetsuo Shoji, Mariko Fukumoto, Eiji Kimoto, Kayo Shinohara, Masanori Emoto, Hideki Tahara, Hidenori Koyama, Eiji Ishimura, Tatsuya Nakatani, Takami Miki, Yoshihiro Tsujimoto, Tsutomu Tabata, Yoshiki Nishizawa
Journal: Kidney International (2002)
Isocitrate Dehydrogenase 1 Is a Novel Plasma Biomarker for the Diagnosis of Non–Small Cell Lung Cancer
Authors: Nan Sun, Zhaoli Chen, Fengwei Tan, Baihua Zhang, Ran Yao, Chengcheng Zhou, Jiagen Li, Yibo Gao, Ziyuan Liu, Xiaogang Tan, Fang Zhou, Max Y.F He, Kang Shao, Ning Li, Bin Qiu, Jian Sun, Yue Yu, Suya Wang, Yuda Zhao, Xuejiao Shi, Jie He
Journal: Clinical Cancer Research (2013)

Abstract Purpose: Effective biomarkers for the diagnosis of non–small cell lung cancer (NSCLC) are needed. We previously showed that isocitrate dehydrogenase 1 (IDH1) is significantly increased in NSCLC tumors. This study aimed to examine the plasma levels of IDH1 in a large patient population to evaluate its effectiveness in NSCLC diagnosis. Experimental Design: The plasma levels of IDH1, CA125, Cyfra21-1, and CEA were assayed by ELISA. Blood samples were obtained from 1,422 participants (943 patients with NSCLC and 479 healthy controls). The samples were randomly divided into a training set and a test set. Receiver operating characteristic and binary logistic regression analyses were applied to evaluate diagnostic efficacy and establish diagnostic mathematical models. Results: Plasma IDH1 levels were significantly higher in patients with NSCLCs than in healthy controls (P &amp;lt; 0.001). The diagnostic use of IDH1 in lung adenocarcinoma [area under curve (AUC): 0.858 and 0.810; sensitivity: 77.1% and 76.2%; specificity: 82.9% and 76.6%; in the training set and test set, respectively] was significantly greater than that of CA125, Cyfra21-1, or CEA (P &amp;lt; 0.001). The model combining IDH1 with CEA, CA125, and Cyfra21-1 was more effective for lung adenocarcinoma diagnosis than IDH1 alone (sensitivity and specificity in the training set: 75.8%, 89.6%; test set: 86.3%, 70.7%). In addition, the plasma levels of IDH1 could contribute to the diagnostic model of lung squamous cell carcinoma. Conclusions: IDH1 can be used as a plasma biomarker for the diagnosis of NSCLCs, particularly lung adenocarcinoma, with relatively high sensitivity and specificity. Clin Cancer Res; 19(18); 5136–45. ©2013 AACR.
Isolation of Papovavirus From Brain Tumor and Urine of a Patient With Wiskott-Aldrich Syndrome
Authors: K. K. Takemoto, A. S. Rabson, M. F. Mullarkey, R. M. Blaese, C. F. Garon, D. Nelson
Journal: JNCI Journal of the National Cancer Institute (1974)

A hemagglutinating papovavirus was isolated from a reticulum cell sarcoma of the brain and from the urine of a patient with Wiskott-Aldrich syndrome. The virus from the brain tumor was isolated by cocultivation of tumor fragments with human fetal brain and VERO cells. Virus from the urine, detected in several samples by electron microscopy of pelleted urine, was subsequently isolated in cell culture. Serum from the patient had high antiviral antibody at least a year before tumor detection. A direct relationship of the virus to the tumor was not established.
Exercise and tachycardia increase NADPH oxidase and ryanodine receptor-2 activity: possible role in cardioprotection
Authors: Gina Sánchez, Matías Escobar, Zully Pedrozo, Pilar Macho, Raúl Domenech, Steffen Härtel, Cecilia Hidalgo, Paulina Donoso
Journal: Cardiovascular Research (2007)

Our objective was to investigate in cardiac muscle the contribution of NADPH oxidase to (a) ryanodine receptor-2 (RyR2) S-glutathionylation and (b) the preconditioning effects of exercise and tachycardia on infarct size following coronary artery occlusion.We measured NADPH oxidase activity, RyR2 S-glutathionylation, and calcium release kinetics in sarcoplasmic reticulum (SR) vesicles isolated from dog ventricular muscle after exercise and tachycardia, plus or minus prior administration of the NADPH oxidase inhibitor apocynin. In ventricular muscle sections, we studied the colocalization of NADPH oxidase and RyR2 by confocal microscopy using fluorescent antibodies. We determined the effect of apocynin on the infarct size produced by occlusion of the descendent anterior coronary artery in animals preconditioned by exercise or tachycardia. Exercise and tachycardia increased NADPH oxidase activity, RyR2 S-glutathionylation, and calcium release rates in isolated SR vesicles. Cardiac muscle sections displayed significant colocalization of NADPH oxidase and RyR2, suggesting direct and specific effects of reactive oxygen species (ROS) produced by NADPH oxidase on RyR2 activation. The NADPH oxidase inhibitor apocynin prevented the increase in RyR2 S-glutathionylation, reduced calcium release activity, and completely prevented the protective effects of exercise and tachycardia on infarct size.The loss of cardioprotection induced by the NADPH oxidase inhibitor suggests that ROS generated by this enzyme are important mediators of the preconditioning response, which presumably involves NADPH oxidase-induced RyR2 S-glutathionylation.
Chronic rhinosinusitis in Europe - an underestimated disease. A GA2LEN study
Authors: D. Hastan, W. J. Fokkens, C. Bachert, R. B. Newson, J. Bislimovska, A. Bockelbrink, P. J. Bousquet, G. Brozek, A. Bruno, S. E. Dahlén, B. Forsberg, M. Gunnbjörnsdóttir, L. Kasper, U. Krämer, M. L. Kowalski, B. Lange, B. Lundbäck, E. Salagean, A. Todo-Bom, P. Tomassen, E. Toskala, C. M. van Drunen, J. Bousquet, T. Zuberbier, D. Jarvis, P. Burney
Journal: Allergy (2011)

To cite this article: Hastan D, Fokkens WJ, Bachert C, Newson RB, Bislimovska J, Bockelbrink A, Bousquet PJ, Brozek G, Bruno A, Dahlén SE, Forsberg B, Gunnbjörnsdóttir M, Kasper L, Krämer U, Kowalski ML, Lange B, Lundbäck B, Salagean E, Todo-Bom A, Tomassen P, Toskala E, van Drunen CM, Bousquet J, Zuberbier T, Jarvis D, Burney P. Chronic rhinosinusitis in Europe – an underestimated disease. A GA2LEN study. Allergy 2011; 66: 1216–1223. Abstract Background: Chronic rhinosinusitis (CRS) is a common health problem, with significant medical costs and impact on general health. Even so, prevalence figures for Europe are unavailable. In this study, conducted by the GA2LEN network of excellence, the European Position Paper on Rhinosinusitis and nasal Polyps (EP3OS) diagnostic criteria are applied to estimate variation in the prevalence of Chronic rhinosinusitis (CRS) for Europe. Method: A postal questionnaire was sent to a random sample of adults aged 15–75 years in 19 centres in Europe. Participants reported symptoms of CRS, and doctor diagnosed CRS, allergic rhinitis, age, gender and smoking history. Definition of CRS was based on the EP3OS diagnostic criteria: the presence of more than two of the symptoms: (i) nasal blockage, (ii) nasal discharge, (iii) facial pain/pressure or (iv) reduction in sense of smell, for >12 weeks in the past year – with at least one symptom being nasal blockage or discharge. Results: Information was obtained from 57 128 responders living in 19 centres in 12 countries. The overall prevalence of CRS by EP3OS criteria was 10.9% (range 6.9–27.1). CRS was more common in smokers than in nonsmokers (OR 1.7: 95% CI 1.6–1.9). The prevalence of self-reported physician-diagnosed CRS within centres was highly correlated with the prevalence of EP3OS-diagnosed CRS. Conclusion: This is the first European international multicentre prevalence study of CRS. In this multicentre survey of adults in Europe, about one in ten participants had CRS with marked geographical variation. Smoking was associated with having CRS in all parts of Europe.
Evolution and Function of the Globin Intergenic Regulatory Regions of the Antarctic Dragonfishes (Notothenioidei: Bathydraconidae)
Authors: Yuk-Ting Lau, Sandra K. Parker, Thomas J. Near, H. William Detrich
Journal: Molecular Biology and Evolution (2011)

As the Southern Ocean cooled to −1.8 °C over the past 40 My, the teleostean clade Notothenioidei diversified and, under reduced selection pressure for an oxygen-transporting apparatus, became less reliant on hemoglobin and red blood cells. At the extreme of this trend, the crown group of Antarctic icefishes (Channichthyidae) lost both components of oxygen transport. Under the decreased selection scenario, we hypothesized that the Antarctic dragonfishes (Bathydraconidae, the red-blooded sister clade to the icefishes) evolved lower blood hemoglobin concentrations because their globin gene complexes (α- and β-globin gene pairs linked by a regulatory intergene) transcribe globin mRNAs less effectively than those of basal notothenioids (e.g., the Nototheniidae [notothens]). To test our hypothesis, we 1) sequenced the α/β-intergenes of the adult globin complexes of three notothen and eight dragonfish species and 2) measured globin transcript levels in representative species from each group. The typical nototheniid intergene was ∼3–4 kb in length. The bathydraconid intergenes resolved into three subclasses (long [3.8 kb], intermediate [3.0 kb], and short [1.5–2.3 kb]) that corresponded to the three subclades proposed for the taxon. Although they varied in length due to indels, the three notothen and eight dragonfish intergenes contained a conserved ∼90-nt element that we have previously shown to be required for globin gene transcription. Using the quantitative polymerase chain reaction, we found that globin mRNA levels in red cells from one notothen species and from one species of each dragonfish subclade were equivalent statistically. Thus, our results indicate that the bathydraconids have evolved adult globin loci whose regulatory intergenes tend to be shorter than those of the more basal nototheniids yet are equivalent in transcriptional efficacy. Their low blood hemoglobin concentrations are most likely due to reduction in hematocrit.
Estrogen Receptor Expression and Efficacy of Docetaxel-Containing Adjuvant Chemotherapy in Patients With Node-Positive Breast Cancer: Results From a Pooled Analysis
Authors: Fabrice Andre, Kristine Broglio, Henri Roche, Miguel Martin, John R. Mackey, Frederique Penault-Llorca, Gabriel N. Hortobagyi, Lajos Pusztai
Journal: Journal of Clinical Oncology (2008)

Several adjuvant chemotherapy trials suggested that cytotoxic treatment is less effective in patients with estrogen receptor (ER)-positive breast cancers. The aim of the present study was to assess the efficacy of adjuvant docetaxel and anthracycline therapy according to ER expression in two randomized clinical trials.Pooled data from two randomized trials, BCIRG001 and PACS01, were examined. Hazard ratios for recurrence and survival were estimated by Cox proportional hazards models and were adjusted for clinical variables. Interaction between docetaxel and ER expression was tested.ER status was available for 3,329 patients (95% of all randomly assigned patients), of whom 75% (n = 2,493) were ER positive. Docetaxel therapy was associated with a 30% reduction in the risk of death (hazard ratio [HR] = 0.70; 95% CI, 0.54 to 0.91) in ER-positive patients and a 31% reduction (HR = 0.69; 95% CI, 0.52 to 0.94) in ER-negative patients. Docetaxel therapy was associated with a 21% reduction in the risk of recurrence (HR = 0.79; 95% CI, 0.66 to 0.93) in ER-positive patients and a 31% reduction (HR = 0.69; 95% CI, 0.54 to 0.97) in ER-negative patients. The interaction between docetaxel therapy and ER status was not statistically significant for either overall survival (P = .87) or disease-free survival (P = .30). ER expression was also not predictive for docetaxel efficacy when it was analyzed as a semi-continuous variable based on percent of positive cells by immunohistochemistry (test for heterogeneity, P = .56 and .86 for overall survival and disease-free survival, respectively).In the pooled analysis of these two trials, docetaxel did not have a statistically significantly different effect on the risk of recurrence or death in ER-positive and ER-negative patients.
Arthropathy in long-term cured acromeagaly is characterised by osteophytes without joint space narrowing: a comparison with generalised osteoarthritis
Authors: M. J. E. Wassenaar, N. R. Biermasz, J. Bijsterbosch, A. M. Pereira, I. Meulenbelt, J. W. A. Smit, F. Roelfsema, H. M. Kroon, J. A. Romijn, M. Kloppenburg
Journal: Annals of the Rheumatic Diseases (2010)

<h3>Objective</h3> To compare the distribution of osteophytes and joint space narrowing (JSN) between patients with acromegaly and primary generalised osteoarthritis to gain insight into the pathophysiological process of growth hormone (GH) and insulin-like growth factor type I (IGF-I)-mediated osteoarthritis. <h3>Methods</h3> We utilised radiographs of the knee and hip joints of 84 patients with controlled acromegaly for a mean of 14.0 years with 189 patients with primary generalised osteoarthritis. Hips and knees with with doubtful or definite osteoarthritis (Kellgren–Lawrence score of ≥1) were compared in the current study. For a semiquantitative assessment of radiological osteoarthritis (range 0–3) osteophytes and JSN of the medial and lateral tibiofemoral and hip joints were scored according to the Osteoarthritis Research Society International atlas. Logistic regression analysis was performed with adjustment for age, sex, body mass index and intrapatient effect. <h3>Results</h3> Knee and hip osteoarthritis in patients with cured acromegaly was characterised by more osteophytosis (OR 4.1–9.9), but less JSN (OR 0.3–0.5) in comparison with patients with primary osteoarthritis. Patients with acromegaly and osteoarthritis had significantly less self-reported functional disability than patients with primary osteoarthritis (p&lt;0.001). Self reported functional disability was associated with JSN rather than with osteophytosis. <h3>Conclusion</h3> Arthropathy caused by GH oversecretion results in osteophytosis and to a lesser extent in JSN. This observation suggests that the GH–IGF-I system is mainly involved in bone formation resulting in osteophytosis, but may possibly protect against cartilage loss.
Estrogen Metabolism and Risk of Breast Cancer in Postmenopausal Women
Authors: Barbara J. Fuhrman, Catherine Schairer, Mitchell H. Gail, Jennifer Boyd-Morin, Xia Xu, Laura Y. Sue, Saundra S. Buys, Claudine Isaacs, Larry K. Keefer, Timothy D. Veenstra, Christine D. Berg, Robert N. Hoover, Regina G. Ziegler
Journal: JNCI Journal of the National Cancer Institute (2012)

Estrogens are recognized causal factors in breast cancer. Interindividual variation in estrogen metabolism may also influence the risk of breast cancer and could provide clues to mechanisms of breast carcinogenesis. Long-standing hypotheses about how estrogen metabolism might influence breast cancer have not been adequately evaluated in epidemiological studies because of the lack of accurate, reproducible, and high-throughput assays for estrogen metabolites. We conducted a prospective case–control study nested within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO). Participants included 277 women who developed invasive breast cancer (case subjects) and 423 matched control subjects; at PLCO baseline, all subjects were aged 55–74 years, postmenopausal and not using hormone therapy, and provided a blood sample. Liquid chromatography–tandem mass spectrometry was used to measure serum concentrations of 15 estrogens and estrogen metabolites, in unconjugated and conjugated forms, including the parent estrogens, estrone and estradiol, and estrogen metabolites in pathways defined by irreversible hydroxylation at the C-2, C-4, or C-16 positions of the steroid ring. We calculated hazard ratios (HRs) approximating risk in highest vs lowest deciles of individual estrogens and estrogen metabolites, estrogens and estrogen metabolites grouped by metabolic pathways, and metabolic pathway ratios using multivariable Cox proportional hazards models. All statistical tests were two-sided. Nearly all estrogens, estrogen metabolites, and metabolic pathway groups were associated with an increased risk of breast cancer; the serum concentration of unconjugated estradiol was strongly associated with the risk of breast cancer (HR = 2.07, 95% confidence interval [CI] = 1.19 to 3.62). No estrogen, estrogen metabolite, or metabolic pathway group remained statistically significantly associated with the risk of breast cancer after adjusting for unconjugated estradiol. The ratio of the 2-hydroxylation pathway to parent estrogens (HR = 0.66, 95% CI = 0.51 to 0.87) and the ratio of 4-hydroxylation pathway catechols to 4-hydroxylation pathway methylated catechols (HR = 1.34, 95% CI = 1.04 to 1.72) were statistically significantly associated with the risk of breast cancer and remained so after adjustment for unconjugated estradiol. More extensive 2-hydroxylation of parent estrogens is associated with lower risk, and less extensive methylation of potentially genotoxic 4-hydroxylation pathway catechols is associated with higher risk of postmenopausal breast cancer.
Patient Safety and Medical Malpractice: A Case Study
Authors: Troyen A. Brennan, Michelle M. Mello
Journal: Annals of Internal Medicine (2003)

The system of tort liability for medical malpractice is frequently criticized for poorly performing its theoretical functions of compensating injured patients, deterring negligence, and dispensing corrective justice. Working from an actual malpractice case involving serious injury but no apparent negligence, the authors explore these criticisms from the perspectives of both the plaintiffpatient and the defendantphysician. They then examine the tort system through the lens of patient safety and conclude that the tensions between the system and patient safety initiatives suggest a need to reexamine our attachment to adversarial dispute resolution in health care. They propose targeted reforms that could improve the functioning of the system and create incentives to improve safety and quality. For a list of questions and answers from the Quality Grand Rounds conference, see the Appendix.
Non-invasive proportional assist and pressure support ventilation in patients with cystic fibrosis and chronic respiratory failure
Authors: A Serra, G Polese, C Braggion, A Rossi
Journal: Thorax (2002)

Background: Patients with advanced cystic fibrosis can benefit from non-invasive positive pressure ventilation (NPPV) for the treatment of acute decompensation as well as for the management of chronic respiratory failure. This study was undertaken to compare the physiological effects of non-invasive proportional assist ventilation (PAV) and pressure support ventilation (PSV) on ventilatory pattern, transcutaneous blood gas tensions, and diaphragmatic effort in stable patients with cystic fibrosis and chronic CO<sub>2</sub> retention. Methods: In 12 patients two periods of spontaneous breathing were followed randomly by PSV (12 (3) cm H<sub>2</sub>O) and PAV (flow assist 4.9 (1.3) cm H<sub>2</sub>O/l.s, volume assist 18.9 (5.1) cm H<sub>2</sub>O/l) set for the patient9s comfort and administered for 40 minutes with 2 cm H<sub>2</sub>O continuous positive airway pressure. Ventilatory pattern, transcutaneous blood gas tensions, and surface diaphragmatic electromyography were measured in the last 10 minutes of each application. Results: On average, both PSV and PAV improved ventilation (+30%), tidal volume (+30%), and transcutaneous CO<sub>2</sub> (−7%) while reducing diaphragmatic activity (−30% with PSV, −20% with PAV). Mean inspiratory airway pressure was lower during PAV than during PSV (9.7 (1.9) and 12.9 (2.7) cm H<sub>2</sub>O, respectively; p&lt;0.05). The mean coefficient of variation of tidal volume was about 20% (range 11–39%) during spontaneous breathing and did not change with either PAV or PSV. Conclusions: These results show that short term administration of nasal PAV and PSV to patients with stable cystic fibrosis with chronic respiratory insufficiency is well tolerated, improves ventilation and blood gas tensions, and unloads the diaphragm.
Domiciliary long-term non-invasive ventilation in COPD: should we select subgroups with a better likelihood to respond to NIV in subsequent randomised controlled trials?
Authors: Jean-Christian Borel, Christophe Pison, Jean-François Timsit, Jean-Louis Pepin
Journal: Thorax (2014)

The efficacy of non-invasive ventilation (NIV) for severe COPD exacerbation has been unambiguously demonstrated. The study by Struik et al recently published in Thorax 1 demonstrates that pursuing nocturnal NIV after acute respiratory failure in patients with COPD exhibiting prolonged hypercapnia >48 h after termination of ventilatory support does not reduce time to readmission or rate of deaths at 1 year. They included a mixed cohort of patients with acute-on-chronic and acute respiratory failures. However, in future studies it may be interesting to select patients with persistent hypercapnia several weeks after the acute exacerbation episode. Nevertheless, long-term …
Radiotherapy and Organ Preservation in Bladder Cancer: Are We Ignoring the Evidence?
Authors: Mary Gospodarowicz
Journal: Journal of Clinical Oncology (2002)

Article Tools EDITORIALS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.20.14.3048 Journal of Clinical Oncology - published online before print November 1, 2016 PMID: 12118016 Radiotherapy and Organ Preservation in Bladder Cancer: Are We Ignoring the Evidence? Mary GospodarowiczxMary GospodarowiczSearch for articles by this author Show More Princess Margaret Hospital, Toronto, Ontario, Canada https://doi.org/10.1200/JCO.2002.20.14.3048 First Page Full Text PDF Figures and Tables © 2002 by American Society of Clinical Oncology