tbuckley/cabot-search huggingface dataset:
Randomized double-blind, placebo-controlled evaluation of oral ondansetron in the prevention of nausea and vomiting associated with fractionated total-body irradiation.
Authors: T R Spitzer, J C Bryson, E Cirenza, R Foelber, M Wallerstadt, C Stout, R L Kunka, P B Plagge, A Dubois
Journal: Journal of Clinical Oncology (1994)

PURPOSE To evaluate oral ondansetron in the prevention of total-body irradiation (TBI)-induced nausea and vomiting. METHODS Twenty patients who received 4 days of TBI as part of their preparative regimen before bone marrow transplantation were randomized to receive either 8-mg oral doses of ondansetron or placebo. Administration of drug was double-blinded. Initial rescue therapy consisted of intravenous (i.v.) ondansetron 0.15 mg/kg following two or more emetic episodes between successive fractions of TBI or five total emetic episodes during the 4 days of therapy. If, after receipt of i.v. ondansetron, patients had two or more emetic episodes between fractions of TBI or five total emetic episodes, additional antiemetics were administered. RESULTS Patients who received oral ondansetron had significantly fewer emetic episodes compared with those who received placebo (P = .005) over the entire 4-day study period. Oral ondansetron was also significantly superior to placebo with respect to the time of onset of emesis or rescue (P = .003). Six of 10 patients treated with oral ondansetron completed the study without additional antiemetic therapy, while none of 10 patients who received placebo completed the study without rescue antiemetic therapy. Six placebo patients who received initial rescue therapy with i.v. ondansetron required no additional antiemetics. No relationships were apparent between peak ondansetron concentration (Cmax) or area under the concentration versus time curve (AUC) and number of emetic episodes. CONCLUSION Oral ondansetron is an effective therapy for the prevention of emesis induced by TBI.
Abstract 1534: Identification of LMX1B as a novel oncogene in human ovarian cancer
Authors: Gayatry Mohapatra, Lei He, Lankai Guo, Vinod Vathipadiekal, Petra Sergent, Whitfield Growdon, Bo Rueda, David Engler, Sandra Orsulic, Michael Birrer
Journal: Cancer Research (2014)

Abstract Ovarian cancers are thought to result from the accumulation of multiple genetic aberrations that transform ovarian and/or fallopian tube surface epithelial cells, allowing for their abnormal growth, proliferation and metastasis. We carried out genome-wide copy-number analysis using array comparative genomic hybridization on a panel of mouse ovarian cancer (OVCA) cell lines previously established in our laboratory. We identified a recurrent focal amplification on mouse chromosomal region 2qB, which contains the LIM homeodomain containing transcription factor 1B (Lmx1b) gene. LMX1B is not expressed in normal human ovary, but is expressed in many human OVCA cell lines and primary tumors. High expression of LMX1B correlates with poor outcome. To clarify the role of LMX1B in ovarian carcinogenesis, we transduced LMX1B into a panel of mouse and human OVCA cell lines and demonstrated that LMX1B strongly promotes migration of cancer cells in culture and accelerates xenograft growth in nude mice. Conversely, knockdown of LMX1B in a human cell line with endogenous high expression of LMX1B inhibits cell migration in vitro and tumor growth in vivo. Microarray analysis of cells overexpressing LMX1B identified NF-κB pathway as a potential mediator of tumor progression and subsequent treatment of NF-κB inhibitor decreased the migratory capacity of these cells. Thus, our data demonstrate that LMX1B functions as an oncogene in OVCA pathogenesis. Citation Format: Gayatry Mohapatra, Lei He, Lankai Guo, Vinod Vathipadiekal, Petra Sergent, Whitfield Growdon, Bo Rueda, David Engler, Sandra Orsulic, Michael Birrer. Identification of LMX1B as a novel oncogene in human ovarian cancer. [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 1534. doi:10.1158/1538-7445.AM2014-1534
Bio-inspired configurable multiscale extracellular matrix-like structures for functional alignment and guided orientation of cells
Authors: Won-Gyu Bae, Jangho Kim, Yun-Hoon Choung, Yesol Chung, Kahp Y. Suh, Changhyun Pang, Jong Hoon Chung, Hoon Eui Jeong
Journal: Biomaterials (2015)
Genetic basis of pulmonary arterial hypertension
Authors: John H Newman, Richard C Trembath, Jane A Morse, Ekkehard Grunig, James E Loyd, Serge Adnot, Fabio Coccolo, Carlo Ventura, John A Phillips, James A Knowles, Bart Janssen, Oliver Eickelberg, Saadia Eddahibi, Phillipe Herve, William C Nichols, Gregory Elliott
Journal: Journal of the American College of Cardiology (2004)
Dose-Intensive Melphalan With Stem Cell Support (MEL100) Is Superior to Standard Treatment in Elderly Myeloma Patients
Authors: Antonio Palumbo, Sabrina Triolo, Chiara Argentino, Sara Bringhen, Alida Dominietto, Cecilia Rus, Paola Omedè, Corrado Tarella, Alessandro Pileri, Mario Boccadoro
Journal: Blood (1999)
Approaches to Validate and Manipulate RNA Targets with Small Molecules in Cells
Authors: Jessica L. Childs-Disney, Matthew D. Disney
Journal: The Annual Review of Pharmacology and Toxicology (2015)

RNA has become an increasingly important target for therapeutic interventions and for chemical probes that dissect and manipulate its cellular function. Emerging targets include human RNAs that have been shown to directly cause cancer, metabolic disorders, and genetic disease. In this review, we describe various routes to obtain bioactive compounds that target RNA, with a particular emphasis on the development of small molecules. We use these cases to describe approaches that are being developed for target validation, which include target-directed cleavage, classic pull-down experiments, and covalent cross-linking. Thus, tools are available to design small molecules to target RNA and to identify the cellular RNAs that are their targets.
<i>CCR</i> 20th Anniversary Commentary: A Genetic Mechanism of Imatinib Resistance in Gastrointestinal Stromal Tumor—Where Are We a Decade Later?
Authors: Cristina R. Antonescu, Ronald P. DeMatteo
Journal: Clinical Cancer Research (2015)

Abstract In the June 1, 2005, issue of Clinical Cancer Research, Antonescu and colleagues defined second-site KIT mutations in gastrointestinal stromal tumor (GIST) as the leading mechanism of acquired resistance to imatinib. Secondary mutations were detectable mainly in KIT exon 11 mutant GISTs after prolonged initial clinical responses. These findings played a critical role in designing the next generation of tyrosine kinase inhibitors. Clin Cancer Res; 21(15); 3363–5. ©2015 AACR. See related article by Antonescu et al., Clin Cancer Res 2005;11(11) June 1, 2005;4182–90
Evaluation of BRCA1 inactivation by promoter methylation as a marker of triple-negative and basal-like breast cancers.
Authors: T. A. Grushko, C. Nwachukwu, S. Charoenthammaraksa, D. Huo, A. Khramtsov, H. Mashek, C. Zhang, J. Xu, C. M. Perou, O. I. Olopade
Journal: Journal of Clinical Oncology (2010)

10510 Background: Triple-negative (ER-, PR-, and HER2-) breast cancer (TNBC) is the most aggressive form of breast disease and is overrepresented in young women and women of African ancestry. Molecular mechanisms specific for TNBC are largely unknown; there is no targeted therapy available. A subgroup of sporadic TNBCs with a basal-like phenotype (BLBC) has morphological features and gene expression profiles similar to tumors from BRCA1 mutation carriers. Promoter methylation inhibit BRCA1 expression resulting in tumor phenotypes similar to those of hereditary BRCA1-mutated tumors. We hypothesize that in sporadic tumors BRCA1inactivation by promoter methylation contributes to the development of TN and BL phenotypes. Methods: Using a combination of methylation-specific PCR, IHC and cDNA microarrays, 198 primary breast cancers were analyzed for methylation of the BRCA1 promoter and expression of ER, PR, HER2, EGFR and ck5/6. Tumor subtypes were determined in191 tumors and correlation with BRCA1 methylation and clinicopathologic features was performed using Stata 9.2 (StataCorp, College Station, TX). Results: Of the 191 tumors, 28% were TNBCs vs 72% Non-TNBCs. Of 174 tumors classified by IHC, 19% were BLBCs, 12% were HER2+/ER-, 52% were Luminal A, 12% were Luminal B and 5% were unclassified cases. BRCA1 methylation was detected in 43% (23/53) TNBCs, compared with 17% (24/138) non-TNBCs (p < 0.0001). The proportion of BRCA1 methylation differed by subtype and was predominant in BLBC (48%, p = 0.002). Luminal A and B tumors were BRCA1 methylated in 18% and 30% of the cases, respectively. In contrast, BRCA1 methylation was less likely to occur in HER2+/ER- tumors (4%). When gene expression signatures were analyzed, BLBC showed the highest proportion of BRCA1-methylated tumors (33%, 5/15) versus other tumor subtypes (5%, 2/39; p = 0.014). Conclusions: BRCA1 inactivation via promoter methylation occurs in almost half of both TNBC and BLBC, suggesting that this epigenetic event drives breast tumor progression toward the TN and BL phenotypes. Our findings justify a common targeted therapy such as PARP inhibitors for both hereditary BRCA1-mutated and sporadic BRCA1-methylated TNBCs. No significant financial relationships to disclose.
Abstract 37: The Positive Inotropic S100a1 Prevents Arrhythmogenic Sarcoplasmic Reticulum Ca2+ Leak And Ventricular Arrhythmias
Authors: Julia Ritterhoff, Mirko Völkers, Andreas Seitz, Kristin Spaich, Karten Peppel, Sven Pleger, Wolfram Zimmermann, Oliver Friedrich, Rainer Fink, Walter Koch, Hugo Katus, Patrick Most
Journal: Circulation Research (2014)

S100A1 has emerged as a key factor in the control of cardiomyocyte (CM) contractile performance. Improved sarcoplasmic reticulum (SR) function with enhanced Ca2+ resequestration appears critical for its cAMP-independent inotropic effects but raises concerns about potential diastolic SR Ca2+ leakage that might trigger fatal arrhythmias. Thus, the goal of this study was to determine the impact of S100A1 on ryanodine receptor 2 (RyR2)-mediated SR Ca2+ leakage in vitro and in vivo. S100A1 association with the RyR2 was significantly diminished (-50%) in failing cardiomyocytes and hearts with S100A1 downregulation, as shown by co-immunofluorescence, co-immunoprecipitation and proximity ligation assay. Adenoviral-mediated S100A1 overexpression (3-4 fold vs. GFP-control) in quiescent NCs (normal CMs) and FCs (failing CMs) decreased SR Ca2+-frequency (-50 and −40% respectively) and protected from β-AR-triggered diastolic Ca2+-waves (-62 and −58% respectively) in electrically stimulated (2Hz) CMs as assessed by epifluorescent and confocal Ca2+ imaging. In multicellular rat engineered heart tissue (EHT), S100A1-overexpression (6-8 fold vs. GFP-control) protected from Ca2+-triggered after-contractions (ACs) (-50%) with preserved enhancement of isometric twitch force (TF, +40%) at 2Hz. S100A1-mediated rescue of contractile failure of endothelin-1-treated EHT (-50% decrease in TF) was associated with protection from Ca2+-triggered ACs. In mice with post-ischemic heart failure, AAV9-mediated therapeutic administration of S100A1 enhanced S100A1/RyR2 association and prevented epinephrine-induced VTs (70% in MI group vs. 30% in MI-S100A1 group). Mechanistically, S100A1-overexpression changed neither PKA/CaMKII RyR2 phosphorylation pattern nor binding of accessory proteins like FKBP12.6, calmodulin or sorcin to RyR2 but enhanced S100A1/RyR2 stoichiometry. Our data provide evidence that S100A1 interaction with the RyR2 can beneficially modulate and reverse diastolic RyR2 function dysfunction. S100A1 appears to convey a rather unique molecular profile combining cAMP-independent inotropy with protection against Ca2+-triggered arrhythmias.
Diagnostic values of scoring systems in the clinical approach to pulmonary thromboembolism
Authors: Aygun Gur, Nur Dilek Bakan, Gungor Camsari, Gulcihan Ozkan, Ayse Yeter, Baris Acikmese
Journal: European Respiratory Journal (2011)

Objective:  The aim of the study was to compare the values of Wells and modified Geneva scoring systems in the diagnosis of PTE.   Methods:  Records of 100 patients admitted with suspected PTE were reviewed. Clinical assessments of the patients were done according to Wells and Geneva scoring systems. D-dimer levels were evaluated. McNemar test, Mann-Whitney U test and ROC curve analysis was used for statistical evaluation.   Results:  Seventy-eight patients were diagnosed as PTE, 22 patients were diagnosed as non PTE. Median Wells score was 5 (0-10) in patients with PTE, 2 (0-5.5) in patients without PTE (p=0.000). Median Geneva score was 7 (0-13) in patients with PTE, 5 (0-7) in patients without PTE (p=0.001). AUC was 0.815 (95% CI; 0,727-0,903) for Wells scores, 0,720 (95% CI; 0,617-0,823) for Geneva scores. For Wells scores ≥3 in PTE diagnosis sensitivity was 83%, specificity was%68 in the study population. Sensitivity was 67%, specificity was 68% for Geneva scores >5 in PTE diagnosis. There was significant difference between Wells and Geneva scoring systems (p=0.047). D-dimer levels were increased in 78 patients and normal in 9 patients. Wells score plus D-dimer testing diagnosed 98.7% of PTE patients, however this caused redundant further testing in patients without PTE.   Conclusion:  Wells scoring system was found to be more sensitive than the modified Geneva system in diagnosis of PTE. The cut-off score for Wells could be kept higher when D-dimer testing is possible, otherwise further diagnostic testing should be considered for PTE diagnosis with Wells score≥3.
Magnolol can induce apoptosis in non-small cell lung cancer via caspase-independent pathway
Authors: Shih-Hung Chu, Po-Len Liu, Jong-Rung Tsai, Inn-Wen Chong
Journal: European Respiratory Journal (2011)

Magnolol is a traditional Chinese herbs drug purified from Magnolia officinalis which has multiple pharmacological properties such as antioxidant and anti-inflammatory effects. Magnolol exhibited remarkable inhibitory effects on tumor growth. However, the effect of Magnolol on non-small cell lung cancer (NSCLC) has not been clarified. In this study, the NSCLC cell lines (A549, H520, H441 and HPAEC) were treated with different concentrations (0∼100μM)of Magnolol for 24 hrs and the cytotoxic effect of Magnolol positively correlated with its concentration. Moreover, the chemotherapy drug Cisplatin at the dose of 25μM had the same cytotoxic effect as Magnolol at 80μM on NSCLC cell lines. Flow cytometry assay revealed that pretreatment with Magnolol at the dose of 80μM for 24 hours could induce apotosis in A549 cells. We also illustrated that membrane potential of mitochondria in A549, H520 and H441 cells started to decrease within 15 min after treatment with Magnolol by staining cancer cells with JC-1 dye. To clarify the mechanism of Magnolol-induced cell apoptosis, the mitochondria and nuclear proteins of NSCLC cell lines were measured by western blotting after treatment with Magnolol at various concentrations for 6hr, and the results revealed that apoptosis-inducing factor (AIF) and endonuclease G (Endo G) induced by Magnolol translocated from mitochondria to nucleus, suggesting that the Magnolol-induced apoptosis is mediated through caspase-independent pathway. In conclusion, Magnolol can induce apoptosis of NSCLC cells. In addition, the apoptosis in NSCLC cells involves, most likely, caspase-independent pathway in NSCLC cells.
Abstract 18895: Left Atrial Ejection Fraction (LAEF) Predicts Cardioembolic Stroke In Patients With Chronic Atrial Fibrillation
Authors: Satoshi Nishiyama, Tetsu Watanabe, Harutoshi Tamura, Shintaro Sasaki, Masahiro Wanezaki, Takanori Arimoto, Hiroki Takahashi, Tetsuro Shishido, Takehiko Miyashita, Takuya Miyamoto, Joji Nitobe, Isao Kubota
Journal: Circulation (2010)

Background: Recently, it was reported that decreased left atrial ejection fraction (LAEF) is a marker of left atrial dysfunction. However, the feasibility of LAEF remains to be determined. We inves...
Category-specific deficits: Insights from semantic dementia and Alzheimer's disease
Authors: Matthew A. Lambon Ralph, Peter Garrard
Journal: Behavioral and Brain Sciences (2001)

Recent investigations and theorising about category-specific deficits have begun to focus upon patients with progressive brain disease such as semantic dementia and Alzheimer's disease. In this commentary we briefly review what insights have been gained from studying patients of this type. We concentrate on four specific issues: the sensory/functional distinction, correlation between features, neuroanatomical considerations, and confounding factors.
Salmonella enterica serotype Virchow: epidemiology, resistance patterns and molecular characterisation of an invasive Salmonella serotype in Israel
Authors: M. Weinberger, H. Solnik-Isaac, D. Shachar, A. Reisfeld, L. Valinsky, N. Andorn, V. Agmon, R. Yishai, R. Bassal, A. Fraser, S. Yaron, D. Cohen
Journal: Clinical Microbiology and Infection (2006)
Assessment of VQ abnormalities in patients with scoliosis
Authors: Amelia Robinson, Matt Rutter, Robert Ross Russell
Journal: European Respiratory Journal (2014)

Background  - We have recently demonstrated that lung ventilation perfusion abnormalities and shunt can be calculated non-invasively. By varying the inspired oxygen levels (PiO2) and measuring arterial saturation (SaO2), we can construct a surrogate oxygen dissociation curve that allows measurement of VQ and of intrapulmonary shunt. Historical reports (Kafer E, J Clin Invest 1976, p825) suggested that VQ abnormalities were common in scoliosis, and were a cause of arterial hypoxaemia. We wanted to test this in a population of children undergoing scoliosis surgery   Methods  - Patients being assessed prior to planned scoliosis surgery were approached.If consented, PiO2 was varied between 14 and 21%, and PaO2 measured using an oximeter. VQ and shunt were calculated using previously described methodology.   Results  - At the present time 9 patients have been studied. All had idiopathic scoliosis, and had mean forced vital capacity between 78 and 103% predicted. The measured shunt in this group was very low (median 0%), and VQ measurements were all within the normal range (range 0.8 - 1.45). No evidence of abnormal VQ could be found in this group, who all tolerated low PiO2 well.   Discussion  - Our data do not currently support there being a significant VQ problem in children with idiopathic scoliosis. In comparison the the patients studied by Kafer, ours had a lesser degree of curvature, and this may have influenced the results. Although poor lung function and hypoxaemia may be found in patients with scoliosis, this early evidence suggests that the cause may be other than in VQ mismatch. However studies are needed in patients with more severe disease.
Long term use of nasal high-flow in COPD
Authors: Jens Bräunlich, Hans-Jürgen Seyfarth, Stefan Hammerschmidt, Hubert Wirtz
Journal: European Respiratory Journal (2013)

Introduction: In the last years nasal high-flow was described as a new tool to treat patients with acute respiratory failure. The effects vary from a better oxygenation, a decrease in breathing rate and dyspnoea scores. At this juncture there exist no data about the application in adult patients with chronic respiratory failure. Method: In this observational prospective study we included patients with COPD, hypercapnia and no exacerbation six weeks before enrollment (n=9). All patients had a complete medication and long-term oxygen therapy. After enrollment the patients completed a blood gas analysis. They received a nasal high-flow device for six weeks. After them, the analysis was repeated. Results: After six weeks, the patients showed a significant decrease in pCO2.  The nHF device was well tolerated. Discussion: Nasal high-flow is able to improve symptoms of respiratory distress. A decrease in breathing rates and in minute volumes indicates a reduction in breathing related work. The main parameter of the efficiency is the reduction in hypercapnia. For this reason nHF could be a powerful tool in the therapy of chronic respiratory failure.
2015 Recommendations for the Management of Polymyalgia Rheumatica: A European League Against Rheumatism/American College of Rheumatology Collaborative Initiative
Authors: Christian Dejaco, Yogesh P. Singh, Pablo Perel, Andrew Hutchings, Dario Camellino, Sarah Mackie, Andy Abril, Artur Bachta, Peter Balint, Kevin Barraclough, Lina Bianconi, Frank Buttgereit, Steven Carsons, Daniel Ching, Maria Cid, Marco Cimmino, Andreas Diamantopoulos, William Docken, Christina Duftner, Billy Fashanu, Kate Gilbert, Pamela Hildreth, Jane Hollywood, David Jayne, Manuella Lima, Ajesh Maharaj, Christian Mallen, Victor Martinez‐Taboada, Mehrdad Maz, Steven Merry, Jean Miller, Shunsuke Mori, Lorna Neill, Elisabeth Nordborg, Jennifer Nott, Hannah Padbury, Colin Pease, Carlo Salvarani, Michael Schirmer, Wolfgang Schmidt, Robert Spiera, David Tronnier, Alexandre Wagner, Madeline Whitlock, Eric L. Matteson, Bhaskar Dasgupta
Journal: Arthritis & Rheumatology (2015)

Abstract Therapy for polymyalgia rheumatica (PMR) varies widely in clinical practice as international recommendations for PMR treatment are not currently available. In this paper, we report the 2015 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) recommendations for the management of PMR. We used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology as a framework for the project. Accordingly, the direction and strength of the recommendations are based on the quality of evidence, the balance between desirable and undesirable effects, patients’ and clinicians’ values and preferences, and resource use. Eight overarching principles and nine specific recommendations were developed covering several aspects of PMR, including basic and follow‐up investigations of patients under treatment, risk factor assessment, medical access for patients and specialist referral, treatment strategies such as initial glucocorticoid (GC) doses and subsequent tapering regimens, use of intramuscular GCs and disease modifying anti‐rheumatic drugs (DMARDs), as well as the roles of non‐steroidal anti‐rheumatic drugs and non‐pharmacological interventions. These recommendations will inform primary, secondary and tertiary care physicians about an international consensus on the management of PMR. These recommendations should serve to inform clinicians about best practices in the care of patients with PMR.
Cannabis smoke and pneumothorax
Authors: Daniel Coutinho, Margarida Dias, Maria Céu Brito, Teresa Shiang
Journal: European Respiratory Journal (2014)

Background: According to recent reports, cannabis use among Portuguese population is 11.7%. The association between primary spontaneous pneumothorax (PSP) and cannabis smoking is still unknown.

Purpose: To determine the frequency of cannabis smokers among patients with a PSP and to compare PSP patients with or without active cannabis use.

Methods: Retrospective study including all patients admitted in a Portuguese tertiary hospital with PSP between January 2011 and December 2012. Socio-demographic variables, tobacco and cannabis smoking status, clinical, radiologic and laboratory findings, treatment outcome and length of hospital stay were recorded. All p-values of <0.05 were considered statistically significant.

Results: Forty-seven patients presented with PSP – 39 male, 8 female; mean age 29.3 years; mean BMI 21.4 kg/m2. Seventeen patients (36.2%) used cannabis (cannabis use unknown in 14.9%). Comparison between cannabis smokers and non-cannabis smokers is presented in Table 1.

View this table:



FEV1 was significantly higher in the cannabis smokers group (p=0.015). No other significant difference was found.

Conclusion: In patients presenting with PSP, cannabis use was higher than in general Portuguese population. Tobacco use was present among all cannabis smokers. Although we have not found a strong association between cannabis use and PSP, it is important to raise awareness for this drug use among these patients, which is not negligible.