tbuckley/cabot-search huggingface dataset:
Prognostic value of microRNAs expression in stage I-IIIA lung adenocarcinoma (AC)
Authors: Marcin Skrzypski, Krzysztof Goryca, Ewa Jassem, Piotr Czapiewski, Wojciech Biernat, Ryszard Pawlowski, Witold Rzyman, Jacek Jassem
Journal: European Respiratory Journal (2013)

Background: About 50% of NSCLC patients (pts) will develop distant metastases following pulmonary resection. Currently, apart from clinical stage at diagnosis, there are no reliable factors to select high-risk pts for adjuvant chemotherapy. We previously demonstrated prognostic value miRNA expression in early squamous cell lung carcinoma (Skrzypski et. al. J Clin Oncol 2010;28;15s). In this study, we investigated the expression of 350 microRNAs in operable AC pts.  Methods: FFPE tumor samples were obtained from 80 stage I-IIIA pts who underwent curative pulmonary resection, 48% of whom subsequently developed distant metastases. Median follow-up of pts who were disease-free was 5.8 years (range, 4.0-9.1 years). RNA was isolated from tumor tissue with RecoverAll kit (Ambion). Expression of 350 miRs was analyzed by RT-PCR (Appliedbiosystems). Raw data were normalized vs. the geometric mean of RNU48 and RNU44 expression. Relative miRs expression was correlated with distant metastases-free survival (MFS) and the mean expression was compared between the groups with and without relapse.  Results: Expression of 41 miRs correlated with MFS in Cox regression analysis and 21 of these showed different level in pts with and without relapse in the t-Student test (both at p  (p  Conclusions: Expression of selected miRs may aid in prediction of distant relapse in AC pts undergoing pulmonary resection.
Results of endoscopic surgery and intralesional steroid therapy for airway compromise due to tracheobronchial Wegener's granulomatosis
Authors: S A R Nouraei, R Obholzer, P W Ind, A D Salama, C D Pusey, F Porter, D J Howard, G S Sandhu
Journal: Thorax (2007)

Upper airway compromise due to tracheobronchial stenosis commonly occurs in patients with Wegener's granulomatosis (WG). There is at present no consensus on the optimal management of this life threatening condition.To assess the results of laryngo-tracheo-bronchoscopy, intralesional steroid therapy, laser surgery and dilatation in managing obstructive tracheobronchial WG.Records of 18 previously untreated stridulous patients with obstructive tracheobronchial WG, treated between 2004 and 2006, were prospectively recorded on an airway database and retrospectively reviewed. Information about patient and lesion characteristics and treatment details were recorded. Treatment progress was illustrated using a timeline plot, and intervention-free intervals were calculated with actuarial analysis.There were nine males and the average age at presentation was 40 (16) years (range 13-74). There were 13 patients with tracheal and five with tracheal and bronchial lesions. The average tracheal lesion height was 8 (3) mm, located 23 (9) mm below the glottis. There were 1, 10 and 7 Myer-Cotton grade I, II and III lesions, respectively. Mean intervention-free interval following minimally invasive treatment was 26 (2.8) months. Following endobronchial therapy, the median intervention-free interval was 22 months (p>0.8 vs tracheal lesions). No patient required a tracheostomy or endoluminal stenting.Intralesional steroid therapy and conservative endoluminal surgery is an effective strategy for treating airway compromise due to active tracheal and bronchial WG, obviating the need for airway bypass or stenting. We recommend the combination of endotracheal dilatation, conservative laser surgery and steroid therapy as the standard of care for treating airway compromise due to obstructive tracheobronchial WG.
Do telephone interventions of patients with COPD prevent readmission
Authors: Marie Lavesen, Rikke Overgaard, Sabine Mazurek, Addie Just, Dorthe Overgaard
Journal: European Respiratory Journal (2012)

Introduction 

In 2009 at Hilleroed Hospital 22% of patients with COPD were readmitted within 30 days and 32 % within 84 days. Literature showed that indicators for readmission were: MRC ≥3, comorbidities, physical inactivity, living alone, poor health-related quality of life and the patients' need for social support.

Aims 

To investigate whether telephone follow-up:

- Reduce number of readmissions

- Increase quality of discharge

- Improve patients' knowledge

The hypothesis tested is that telephone interventions provide greater security for patients with COPD in order to support self-management and reduce number of readmission.

Methods 

A randomized trial were performed with an intervention group (N=115), who was contacted by a nurse 3 & 30 days after discharge. Additional telephone calls were offered if needed.

Through appreciated inquiry the patients' experience due to the admission was clarified. Dialog and providing knowledge were used to support self-management and coping with exacerbations. After 30 days the patients' answered a questionnaire containing generic questions about health status, managing COPD and an evaluation of the intervention. The control group (N=97) was also contacted on day 30 and answered the same questionnaire except questions about evaluation. SPSS statistics were used to analyze data.

Results 

The preliminary results indicate that there was no effect on the number of readmissions. The majority of the intervention group felt secure and content knowing that a nurse will provide a follow-up call. The ability to contact health professionals when needed was important.

Conclusion 

Telephone follow-up did not reduce the number of readmissions for patients with COPD compared to a control group.
Complete Elimination of Colorectal Tumor Xenograft by Combined Manganese Superoxide Dismutase with Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand Gene Virotherapy
Authors: Yanhong Zhang, Jinfa Gu, Lili Zhao, Lingfeng He, Wenbin Qian, Jinhui Wang, Yigang Wang, Qijun Qian, Cheng Qian, Jian Wu, Xin Yuan Liu
Journal: Cancer Research (2006)

Abstract Manganese superoxide dismutase (MnSOD) is a latent tumor suppressor gene. To investigate the therapeutic effect of MnSOD and its mechanisms, a replication-competent recombinant adenovirus with E1B 55-kDa gene deletion (ZD55) was constructed, and human MnSOD and tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) genes were inserted to form ZD55-MnSOD and ZD55-TRAIL. ZD55-MnSOD exhibited an inhibition in tumor cell growth ∼1,000-fold greater than Ad-MnSOD. ZD55-TRAIL was shown to induce the MnSOD expression in SW620 cells. Accordingly, by the combined use of ZD55-MnSOD with ZD55-TRAIL (i.e., “dual gene virotherapy”), all established colorectal tumor xenografts were completely eliminated in nude mice. The evidence exists that the MnSOD overexpression led to a slower tumor cell growth both in vitro and in vivo as a result of apoptosis caused by MnSOD and TRAIL overexpression after adenoviral transduction. Our results showed that the production of hydrogen peroxide derived from MnSOD dismutation activated caspase-8, which might down-regulate Bcl-2 expression and induce Bax translocation to mitochondria. Subsequently, Bax translocation enhanced the release of apoptosis-initiating factor and cytochrome c. Cytochrome c finally triggered apoptosis by activating caspase-9 and caspase-3 in apoptotic cascade. Bax-mediated apoptosis seems to be dependent on caspase-8 activation because the inhibition of caspase-8 prevented Bid processing and Bax translocation. In conclusion, our dual gene virotherapy completely eliminated colorectal tumor xenografts via enhanced apoptosis, and this novel strategy points toward a new direction of cancer treatment. (Cancer Res 2006; 66(8): 4291-8)
Use of BCG as an immunostimulant after resection of carcinoma of the lung: a two-year assessment of a trial of 500 patients.
Authors: F R Edwards
Journal: Thorax (1979)

BCG (Glaxo) (0.5 ml = 5 X 10(6) organisms) was given subdermally to 250 patients ten days after resection of a lung carcinoma to stimulate the immune system. Increased activity of lymphocytes and macrophages could possibly result in the destruction of small extrapulmonary tumour deposits that were previously unidentified. The two-year survival of this group of patients was compared with 250 controls not receiving BCG after operation. A comparative analysis of the sex, histological types, and lymph node involvement in relation to the survivals occurring in these two groups showed that the administration of BCG by the method described produced a numerically greater survival rate, which was particularly noticeable in the women. None of these figures, however, is statistically significant. It would be unwise to draw any final conclusion until a five-year survey has been completed.
Differential effects of nasal continuous positive airway pressure on reversible or fixed upper and lower airway obstruction
Authors: CH Wang, HC Lin, TJ Huang, CT Yang, CT Yu, HP Kuo
Journal: European Respiratory Journal (1996)

Our study was to assess whether there were differential effects of nasal continuous positive airway pressure (nCPAP) on different kinds of obstruction in either upper or lower airways in patients with chronic obstructive pulmonary disease (COPD). nCPAP (6 cmH2O for ten minutes) was applied to 7 patients with reversible extrathoracic upper airway obstruction (RUAO) and 3 patients with fixed extrathoracic upper airway obstruction (FUAO). Eighteen stable asthmatics, receiving methacholine challenge to induce a more than 20% reduction in FEV1, were randomly investigated for the effect of nCPAP or sham pressure on reversible lower airway obstruction. Nine stable COPD patients were enrolled to study the effect on irreversible lower airway obstruction. Maximal expiratory and inspiratory flow volume curves and dyspnoea scores were obtained before and after immediate withdrawal of nCPAP. In the RUAO group, nCPAP significantly improved stridor and dyspnoea scores, decreased the ratio of FEF50/FIF50 from 2.05 +/- 0.25 to 1.42 +/- 0.16, and increased peak inspiratory flow (PIF) as well as forced inspiratory vital capacity by 26 +/- 8% and 9 +/- 4%, respectively. In expiratory phase, there was no significant change in pulmonary functions. In asthmatics, nCPAP significantly reversed methacholine-induced bronchoconstriction increasing forced vital capacity by 10 +/- 3%, FEV1 by 15 +/- 4% and PIF by 32 +/- 11%. nCPAP significantly increased the response to bronchodilators. The improvement in airflow rate persisted for at least 5 min after nCPAP withdrawal and was highly correlated with the response to bronchodilators. There was no significant effect of nCPAP on airflow rate in COPD patients. Subjective dyspnoea score changes paralleled the pulmonary function improvement. We conclude that there are differential effects of nCPAP on airflow rates in patients with different nature of airway obstruction. Patients with airway obstruction caused by structural changes may not benefit from the use of nCPAP in improving airflow rates.
Shake up of mental healthcare provision could save around 0.5bn a year
Authors: A. O'Dowd
Journal: BMJ (2010)

A large shake up of the way mental health services are organised and provided could save hundreds of millions of pounds a year and improve the care of patients, policy experts say in a new report.

The report, published on 2 December, claims that earlier and more effective intervention when people become unwell could improve their care significantly and save the NHS money.

The joint report from the health policy think tank the King’s Fund and the Centre for Mental Health, which works to improve the quality of life for people with mental health problems, found several ways to change mental health services that could contribute to …
Identification of the alpha 3 chain of type IV collagen as the common autoantigen in antibasement membrane disease and Goodpasture syndrome.
Authors: R Kalluri, C B Wilson, M Weber, S Gunwar, A M Chonko, E G Neilson, B G Hudson
Journal: Journal of the American Society of Nephrology (1995)

Antiglomerular basement membrane (GBM) antibodies can cause glomerulonephritis or pulmonary hemorrhage by themselves or Goodpasture syndrome when they occur together. It is unknown if variations in antibody reactivity contribute to the different patterns of organ involvement seen in this disease. This study examines the reactivity of the alpha 1-alpha 6 NC1 domains of Type IV collagen, the putative autoantigen, in sera from patients with anti-GBM antibodies after various clinical presentations of lung hemorrhage and renal injury. Serum or plasma containing anti-GBM antibodies from 35 patients with combined glomerulonephritis and pulmonary hemorrhage, 19 with glomerulonephritis alone, and 4 with pulmonary hemorrhage alone were compared with samples from 19 normal controls and 32 patients with other kidney diseases. Four different immunologic assays were performed with bovine alpha 1-alpha 6(IV) and recombinant human type alpha 1-alpha 5(IV) collagen NC1 domains. The study found that the anti-GBM antibodies from all patients reacted with the alpha 3(IV) NC1 (85% exclusively). Additional limited reactivity with the alpha 1(IV) NC1 and alpha 4(IV) NC1 was found in 15 and 3%, respectively. This non-alpha 3(IV) NC1 reactivity was most frequent in the patients with anti-GBM antibodies and glomerulonephritis alone. None of the patients had reactivity to other basement membrane components like laminin, fibronectin, heparan sulfate proteoglycan, entactin, or the 7S and triple helical fragments of Type IV collagen. The observed alpha-chain NC1 reactivity was confined to patients with anti-GBM antibodies with no additional reactivities detected among a large number of other kidney diseases controls. The correlation of alpha 1-alpha 6(IV) NC1 reactivity in a large number of patients with anti-GBM antibodies defined by classic assays definitively establishes that reactivity to alpha 3(IV) NC1 domains is both sufficient and necessary for the expression of autoimmune disease directed to the NC1 domain of Type IV collagen. On the basis of the evidence, the classification of antibasement membrane disease and Goodpasture syndrome as anti-Type IV collagen disease is proposed.
Ventricular Constraint Using the Acorn Cardiac Support Device Reduces Myocardial Akinetic Area in an Ovine Model of Acute Infarction
Authors: James J. Pilla, Aaron S. Blom, Daniel J. Brockman, Frank Bowen, Qing Yuan, Joseph Giammarco, Victor A. Ferrari, Joseph H. Gorman, Robert C. Gorman, Michael A. Acker
Journal: Circulation (2002)

Left ventricular remodeling secondary to acute myocardial infarction (AMI) is characterized by ventricular dilatation and regional akinesis. In this study, we investigated the effect of passive constraint on akinetic area development.The effect of passive constraint on akinetic area was investigated in 10 sheep using tissue-tagging magnetic resonance imaging (MRI). A baseline MRI study was followed by the creation of an anterior infarct. After 1 week, the animals received a second MRI study. A cardiac support device (CSD) was then placed over the epicardium in 5 sheep whereas the remaining animals served as controls. A terminal study was performed at the 2-month postinfarct in both groups. The akinetic area at 1-week postinfarct was similar in both groups. At the terminal time-point, the akinetic area in the control group was similar to the 1-week time-point whereas in the CSD group, the area of akinesis decreased (P=0.001). A comparison of the 2 groups at the terminal time-point demonstrates a significantly diminished area of akinesis in the CSD group (P=0.004). The relative area of akinesis followed a similar pattern. End-systolic and end-diastolic wall thickness was significantly greater in the CSD group at terminal (P=0.001). In addition, the minimum wall thickness was greater in the CSD group compared with the controls (P=0.04).Passive constraint reduced akinetic area development secondary to AMI. The attenuation of regional wall stress may prevent the incorporation of the border zone into the infarct, decreasing infarct size and providing a promising new therapy for patients after an AMI.
<i>PXR</i> Pharmacogenetics: Association of Haplotypes with Hepatic <i>CYP3A4</i> and <i>ABCB1</i> Messenger RNA Expression and Doxorubicin Clearance in Asian Breast Cancer Patients
Authors: Edwin Sandanaraj, Suman Lal, Viknesvaran Selvarajan, London Lucien Ooi, Zee Wan Wong, Nan Soon Wong, Peter Cher Siang Ang, Edmund J.D. Lee, Balram Chowbay
Journal: Clinical Cancer Research (2008)

Abstract Purpose: To characterize pregnane X receptor (PXR) polymorphic variants in healthy Asian populations [Chinese, Malay and Indian (n = 100 each)], and to investigate the association between PXR haplotypes and hepatic mRNA expression of PXR and its downstream target genes, CYP3A4 and ABCB1, as well as their influence on the clearance of doxorubicin in Asian breast cancer patients. Experimental Design: PXR genotyping was done by direct DNA sequencing, and PXR haplotypes and haplotype clusters were derived by expectation-maximization algorithm. Genotype-phenotype correlations were done using Mann-Whitney U test and Kruskal-Wallis test. Results: Significant interethnic variations were observed in PXR pharmacogenetics among the three Asian ethnic groups. The expression of PXR mRNA in liver tissues harboring the PXR*1B haplotype clusters was 4-fold lower compared with the non-PXR*1B (*1A + *1C) haplotype clusters [PXR*1B versus PXR*1A; P = 0.015; PXR*1B versus PXR*1C; P = 0.023]. PXR*1B-bearing liver tissues were associated with significantly lower expression of CYP3A4 (PXR*1B versus non-PXR*1B, P = 0.030) and ABCB1 (PXR*1B versus non-PXR*1B, P = 0.060) compared with non–PXR*1B-bearing liver tissues. Doxorubicin clearance in breast cancer patients harboring the PXR*1B haplotypes was significantly lower compared with patients carrying the non-PXR*1B haplotypes [PXR*1B versus non-PXR*1B, CL/BSA (L h−1 m−2): 20.84 (range, 8.68-29.24) versus 24.85 (range, 13.80-55.66), P = 0.022]. Conclusions: This study showed that PXR*1B was associated with reduced hepatic mRNA expression of PXR and its downstream targets, CYP3A4 and ABCB1. Genotype-phenotype correlates in breast cancer patients showed PXR*1B to be significantly associated with lower doxorubicin clearance, suggesting that PXR haplotype constitution could be important in influencing interindividual and interethnic variations in disposition of its putative drug substrates.
Defective Acidification in Human Breast Tumor Cells and Implications for Chemotherapy
Authors: Nihal Altan, Yu Chen, Melvin Schindler, Sanford M. Simon
Journal: The Journal of Experimental Medicine (1998)

Multidrug resistance (MDR) is a significant problem in the treatment of cancer. Chemotherapeutic drugs distribute through the cyto- and nucleoplasm of drug-sensitive cells but are excluded from the nucleus in drug-resistant cells, concentrating in cytoplasmic organelles. Weak base chemotherapeutic drugs (e.g., anthracyclines and vinca alkaloids) should concentrate in acidic organelles. This report presents a quantification of the pH for identified compartments of the MCF-7 human breast tumor cell line and demonstrates that (a) the chemotherapeutic Adriamycin concentrates in acidified organelles of drug-resistant but not drug-sensitive cells; (b) the lysosomes and recycling endosomes are not acidified in drug-sensitive cells; (c) the cytosol of drug-sensitive cells is 0.4 pH units more acidic than the cytosol of resistant cells; and (d) disrupting the acidification of the organelles of resistant cells with monensin, bafilomycin A1, or concanamycin A is sufficient to change the Adriamycin distribution to that found in drug-sensitive cells, rendering the cell vulnerable once again to chemotherapy. These results suggest that acidification of organelles is causally related to drug resistance and is consistent with the hypothesis that sequestration of drugs in acidic organelles and subsequent extrusion from the cell through the secretory pathways contribute to chemotherapeutic resistance.
DNA Repair: Enzymatic Mechanisms and Relevance to Drug Response
Authors: Stephen G. Chaney, Aziz Sancar
Journal: JNCI Journal of the National Cancer Institute (1996)

A number of chemotherapeutic agents, such as platinum drugs, nitrogen mustards, and chloroethylnitrosoureas, act by forming bifunctional DNA adducts. It is likely that abortive attempts to replicate and/or repair the damaged DNA cause chromosome aberrations and breakage, leading to cell death. Any substantial increase in cellular capacity to repair damaged DNA may result in resistance to chemotherapeutic agents. In this review, we examine the types of DNA adducts formed by the major classes of chemotherapeutic agents, the enzymatic pathways that play a role in the repair of those adducts, the evidence that DNA repair is enhanced in drug-resistant cell lines and tumors, and strategies for utilizing selective inhibition of DNA repair to overcome resistance.
A quantitative literature-curated gold standard for kinase-substrate pairs
Authors: Sara Sharifpoor, Alex N Nguyen Ba, Ji-Young Young, Dewald van Dyk, Helena Friesen, Alison C Douglas, Christoph F Kurat, Yolanda T Chong, Karen Founk, Alan M Moses, Brenda J Andrews
Journal: Genome biology (2011)

We describe the Yeast Kinase Interaction Database (KID, http://www.moseslab.csb.utoronto.ca/KID/ ), which contains high- and low-throughput data relevant to phosphorylation events. KID includes 6,225 low-throughput and 21,990 high-throughput interactions, from greater than 35,000 experiments. By quantitatively integrating these data, we identified 517 high-confidence kinase-substrate pairs that we consider a gold standard. We show that this gold standard can be used to assess published high-throughput datasets, suggesting that it will enable similar rigorous assessments in the future.
Cause of Death in Patients with Reduced Kidney Function
Authors: Stephanie Thompson, Matthew James, Natasha Wiebe, Brenda Hemmelgarn, Braden Manns, Scott Klarenbach, Marcello Tonelli
Journal: Journal of the American Society of Nephrology (2015)

Information on common causes of death in people with CKD is limited. We hypothesized that, as eGFR declines, cardiovascular mortality and mortality from infection account for increasing proportions of deaths. We calculated eGFR using the CKD Epidemiology Collaboration equation for residents of Alberta, Canada who died between 2002 and 2009. We used multinomial logistic regression to estimate unadjusted and age- and sex-adjusted differences in the proportions of deaths from each cause according to the severity of CKD. Cause of death was classified as cardiovascular, infection, cancer, other, or not reported using International Classification of Diseases codes. Among 81,064 deaths, the most common cause was cancer (31.9%) followed by cardiovascular disease (30.2%). The most common cause of death for those with eGFR≥60 ml/min per 1.73 m2 and no proteinuria was cancer (38.1%); the most common cause of death for those with eGFR<60 ml/min per 1.73 m2 was cardiovascular disease. The unadjusted proportion of patients who died from cardiovascular disease increased as eGFR decreased (20.7%, 36.8%, 41.2%, and 43.7% of patients with eGFR≥60 [with proteinuria], 45–59.9, 30–44.9, and 15–29.9 ml/min per 1.73 m2, respectively). The proportions of deaths from heart failure and valvular disease specifically increased with declining eGFR along with the proportions of deaths from infectious and other causes, whereas the proportion of deaths from cancer decreased. In conclusion, we found an inverse association between eGFR and specific causes of death, including specific types of cardiovascular disease, infection, and other causes, in this cohort.