tbuckley/cabot-search huggingface dataset:
Integrative Genomics Identifies Molecular Alterations that Challenge the Linear Model of Melanoma Progression
Authors: Amy E. Rose, Laura Poliseno, Jinhua Wang, Michael Clark, Alexander Pearlman, Guimin Wang, Eleazar C. Vega y Saenz de Miera, Ratna Medicherla, Paul J. Christos, Richard Shapiro, Anna Pavlick, Farbod Darvishian, Jiri Zavadil, David Polsky, Eva Hernando, Harry Ostrer, Iman Osman
Journal: Cancer Research (2011)

Superficial spreading melanoma (SSM) and nodular melanoma (NM) are believed to represent sequential phases of linear progression from radial to vertical growth. Several lines of clinical, pathologic, and epidemiologic evidence suggest, however, that SSM and NM might be the result of independent pathways of tumor development. We utilized an integrative genomic approach that combines single nucleotide polymorphism array (6.0; Affymetrix) with gene expression array (U133A 2.0; Affymetrix) to examine molecular differences between SSM and NM. Pathway analysis of the most differentially expressed genes between SSM and NM (N = 114) revealed significant differences related to metabolic processes. We identified 8 genes (DIS3, FGFR1OP, G3BP2, GALNT7, MTAP, SEC23IP, USO1, and ZNF668) in which NM/SSM-specific copy number alterations correlated with differential gene expression (P < 0.05; Spearman's rank). SSM-specific genomic deletions in G3BP2, MTAP, and SEC23IP were independently verified in two external data sets. Forced overexpression of metabolism-related gene MTAP (methylthioadenosine phosphorylase) in SSM resulted in reduced cell growth. The differential expression of another metabolic-related gene, aldehyde dehydrogenase 7A1 (ALDH7A1), was validated at the protein level by using tissue microarrays of human melanoma. In addition, we show that the decreased ALDH7A1 expression in SSM may be the result of epigenetic modifications. Our data reveal recurrent genomic deletions in SSM not present in NM, which challenge the linear model of melanoma progression. Furthermore, our data suggest a role for altered regulation of metabolism-related genes as a possible cause of the different clinical behavior of SSM and NM.
Intra-articular guanethidine injection for resistant shoulder pain: a preliminary double blind study of a novel approach.
Authors: K Gado, P Emery
Journal: Annals of the Rheumatic Diseases (1996)

OBJECTIVE: To study the effect of intraarticular (IA) sympathetic blockade for the relief of resistant shoulder pain. METHODS: Eighteen patients with shoulder pain resistant to conventional treatment were allocated randomly to two groups, to receive either IA guanethidine 20 mg or IA saline. They were assessed for pain, and range of active movements, before injection and at one, four, and eight weeks after injection. RESULTS: There were no significant differences between groups, but the group receiving guanethidine showed greater improvement in pain relief at all three follow up visits compared with those receiving placebo (9% v 7% at one week; 15% v 6% at four weeks and 36% v 16% at eight weeks). The improvement reached significance (p &lt; 0.05) at the eight week visit compared with baseline. The range of movement was not significantly improved in either group. CONCLUSION: The results suggest that IA guanethidine produced measurable improvement in resistant shoulder pain and that further studies of this novel approach are indicated.
Cochrane corner: psychological interventions for individuals with cystic fibrosis and their families: Table 1
Authors: Lutz Goldbeck, Astrid Fidika, Marion Herle, Alexandra L Quittner
Journal: Thorax (2015)

Psychological issues associated with cystic fibrosis may arise from the patients' lifelong disease- and treatment-related burden. This Cochrane Review aimed to determine psychosocial and physical outcomes of psychological interventions. Trial registries, databases and professional networks were used to identify relevant studies. Altogether, 16 studies involving 556 participants were included. They were heterogeneous in their methods, design, target groups, and outcomes. Overall, the current evidence for psychological interventions is insufficient. Preliminary evidence was available for interventions targeting specific aspects of the treatment regimen, such as behavioural nutrition interventions.
Digital gene expression profiling of primary acute lymphoblastic leukemia cells
Authors: J Nordlund, A Kiialainen, O Karlberg, E C Berglund, H Göransson-Kultima, M Sønderkær, K L Nielsen, M G Gustafsson, M Behrendtz, E Forestier, M Perkkiö, S Söderhäll, G Lönnerholm, A-C Syvänen
Journal: Leukemia (2011)

We determined the genome-wide digital gene expression (DGE) profiles of primary acute lymphoblastic leukemia (ALL) cells from 21 patients taking advantage of 'second-generation' sequencing technology. Patients included in this study represent four cytogenetically distinct subtypes of B-cell precursor (BCP) ALL and T-cell lineage ALL (T-ALL). The robustness of DGE combined with supervised classification by nearest shrunken centroids (NSC) was validated experimentally and by comparison with published expression data for large sets of ALL samples. Genes that were differentially expressed between BCP ALL subtypes were enriched to distinct signaling pathways with dic(9;20) enriched to TP53 signaling, t(9;22) to interferon signaling, as well as high hyperdiploidy and t(12;21) to apoptosis signaling. We also observed antisense tags expressed from the non-coding strand of ~50% of annotated genes, many of which were expressed in a subtype-specific pattern. Antisense tags from 17 gene regions unambiguously discriminated between the BCP ALL and T-ALL subtypes, and antisense tags from 76 gene regions discriminated between the 4 BCP subtypes. We observed a significant overlap of gene regions with alternative polyadenylation and antisense transcription (P<1 × 10(-15)). Our study using DGE profiling provided new insights into the RNA expression patterns in ALL cells.
Peak exercise response in relation to tissue depletion in patients with chronic obstructive pulmonary disease
Authors: EM Baarends, AM Schols, R Mostert, EF Wouters
Journal: European Respiratory Journal (1997)

In several studies a correlation between body weight and peak exercise capacity has been found in patients with chronic obstructive pulmonary disease (COPD). In the present study a thorough analysis of the relationship between body composition and peak exercise performance was executed in 62 patients with clinically stable COPD. This was based on the hypothesis that particularly muscle mass, as the largest constituent of both fat-free mass (FFM) and body cell mass, is related to exercise capacity. Body composition was assessed using deuterium and bromide dilution techniques, to measure total body water (TBW) and extracellular water. From these measurements FFM:TBW/0.73, the ratio of ECW/intracellular water (ICW) and ICW-index (ICW/height2) were calculated. Peak exercise performance was measured using an incremental cycle ergometry test. The transfer factor of the lung for carbon monoxide (TL,CO) intrathoracic gas volume (ITGV), maximal expiratory and inspiratory mouth pressure, forced expiratory volume in one second (FEV1), FFM-index (FFM/height2), body mass index (weight/height2) and ICW-index correlated strongly (p&lt;0.01) to peak oxygen consumption (V'O2). The ratio ECW/ICW correlated only weakly, but significantly, with peak V'O2 (r=-0.25, p&lt;0.05). Stepwise regression analysis demonstrated that FFM-index and TL,CO explained 53% of the variation in peak V'O2. The results of this study furthermore indicate that severe FFM depletion is related to a blunted tidal volume response to peak exercise, a decreased peak oxygen pulse and an early anaerobic metabolism in patients with COPD. Depletion of muscle mass, measurable by assessment of fat-free mass, significantly effects peak oxygen consumption, ventilatory response, the oxygen pulse and anaerobic energy metabolism in patients with chronic obstructive pulmonary disease.
The prognostic significance of K-ras, p53, and APC mutations in colorectal carcinoma
Authors: A Conlin
Journal: Gut (2005)

<b>Background:</b> Accumulation of molecular alterations, including mutations in Kirsten-ras (K-ras), p53, and adenomatous polyposis coli (APC), contribute to colorectal carcinogenesis. Our group has previously characterised a panel of sporadic colorectal adenocarcinomas for mutations in these three genes and has shown that p53 and K-ras mutations rarely occur in the same colorectal tumour. This suggests that mutations in these genes are on separate pathways to colorectal cancer development and may influence patient prognosis independently. <b>Aims:</b> To correlate the presence or absence of mutations in K-ras, p53, and APC with survival in a cohort of colorectal cancer patients. <b>Patients:</b> A series of 107 inpatients treated surgically for colorectal cancer in Tayside, Scotland between November 1997 and December 1999. <b>Methods:</b> Colorectal tumours were characterised for mutations in K-ras, p53, and APC. Kaplan-Meier survival curves were constructed using overall survival and disease specific survival as the primary end points. Patient survival was analysed using the log rank test and Cox proportional hazards model. <b>Results:</b> Patients with K-ras mutations had significantly poorer overall survival than patients without K-ras mutations (p = 0.0098). Multivariate analysis correcting for Dukes’ stage, age, and sex confirmed this (hazard ratio 2.9 (95% confidence interval 1.4–6.2); p = 0.0040). K-ras mutations were also significantly associated with poorer disease specific survival. The presence of APC and p53 mutations did not affect survival in this cohort of patients (p = 0.9034 and p = 0.8290, respectively). <b>Conclusions:</b> Our data indicate that the presence of K-ras mutations predicts poor patient prognosis in colorectal cancer, independently of tumour stage.
Axitinib Is an Active Treatment for All Histologic Subtypes of Advanced Thyroid Cancer: Results From a Phase II Study
Authors: Ezra E.W. Cohen, Lee S. Rosen, Everett E. Vokes, Merrill S. Kies, Arlene A. Forastiere, Francis P. Worden, Madeleine A. Kane, Eric Sherman, Sinil Kim, Paul Bycott, Michael Tortorici, David R. Shalinsky, Katherine F. Liau, Roger B. Cohen
Journal: Journal of Clinical Oncology (2008)

Patients with advanced, incurable thyroid cancer not amenable to surgery or radioactive iodine ((131)I) therapy have few satisfactory therapeutic options. This multi-institutional study assessed the activity and safety of axitinib, an oral, potent, and selective inhibitor of vascular endothelial growth factor receptors (VEGFR) 1, 2, and 3 in patients with advanced thyroid cancer. Patients with thyroid cancer of any histology that was resistant or not appropriate for (131)I were enrolled onto a single-arm phase II trial to receive axitinib orally (starting dose, 5 mg twice daily). Objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors was the primary end point. Secondary end points included duration of response, progression-free survival (PFS), overall survival, safety, and modulation of soluble (s) VEGFR. Sixty patients were enrolled. Partial responses were observed in 18 patients, yielding an ORR of 30% (95% CI, 18.9 to 43.2). Stable disease lasting > or = 16 weeks was reported in another 23 patients (38%). responses were noted in all histologic subtypes. Median PFS was 18.1 months (95% CI, 12.1 to not estimable). Axitinib was generally well tolerated, with the most common grade > or = 3 treatment-related adverse event being hypertension (n = 7; 12%). Eight patients (13%) discontinued treatment because of adverse events. Axitinib selectively decreased sVEGFR-2 and sVEGFR-3 plasma concentrations versus sKIT, demonstrating its targeting of VEGFR. Axitinib is a selective inhibitor of VEGFR with compelling antitumor activity in all histologic subtypes of advanced thyroid cancer.
Study of Mendelian forms of Crohn's disease in Saudi Arabia reveals novel risk loci and alleles
Authors: Nisha Patel, Mohammad I El Mouzan, Sulaiman M Al-Mayouf, Nouran Adly, Jawahir Y Mohamed, Mohammad A Al Mofarreh, Niema Ibrahim, Yong Xiong, Qi Zhao, Khalid A Al-Saleem, Fowzan S Alkuraya
Journal: Gut (2014)

Sir,

We read with interest the article by Uhlig on the Mendelian forms of IBD.1 Mendelian forms of Crohn's disease (CD) are rare but can establish a causal link that is not usually possible by the genome-wide association study (GWAS) design. In order to accelerate the discovery of Mendelian CD, we recruited four cooperative families in which the healthy consanguineous parents had at least two affected children with early onset CD (<10 years of age), consistent with autosomal recessive inheritance (see online supplementary figure S1). With informed consent according to an Institutional Review Board approved protocol (KFSHRC RAC# 2121053), we proceeded with autozygosity mapping using AgileMultiIdeogram (http://dna.leeds.ac.uk/agile/AgileMultiIdeogram/) followed by whole-exome sequencing (WES) as previously described.2 Online supplementary table S1 shows the iterative filtering of the resulting variants based on homozygosity, predicted pathogenicity, location within the autozygome and novelty.

Family 1 consists of first cousin parents, four affected and seven unaffected children. The four affected children presented with a remarkably similar clinical picture that consists of early onset IBD and severe and debilitating arthropathy. The four affected siblings shared …
Small-Cell Cancers, and an Unusual Reaction to Chemotherapy
Authors: Suleiman Massarweh, Michael Lewitton, Uday Popat, Garrett R. Lynch
Journal: Journal of Clinical Oncology (2003)

Article Tools DIAGNOSIS IN ONCOLOGY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2003.06.169 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12805345 Small-Cell Cancers, and an Unusual Reaction to Chemotherapy CASE 2. SYNCHRONOUS RENAL CELL CARCINOMA AND LIMITED-STAGE SMALL-CELL LUNG CANCER Suleiman MassarwehxSuleiman MassarwehSearch for articles by this author , Michael LewittonxMichael LewittonSearch for articles by this author , Uday PopatxUday PopatSearch for articles by this author , Garrett R. LynchxGarrett R. LynchSearch for articles by this author Show More Ben Taub General Hospital, Baylor College of Medicine, Houston, TX https://doi.org/10.1200/JCO.2003.06.169 First Page Full Text PDF Figures and Tables © 2003 by American Society of Clinical Oncology
Berberine Alone and in Conjunction With Immunomodulators Down-regulates Pro-inflammatory CD4+ T-Cells: Implications for a Combined Treatment of Inflammatory Bowel Diseases
Authors: N. Salomon, E. Fudim, O. Picard, M. Yavzori, D. Gamus, R. Elyakim, S. Ben-Horin
Journal: Clinical Gastroenterology and Hepatology (2014)
Ankylosing spondylitis: an autoimmune disease?
Authors: H J Lakomek, M Plomann, C Specker, M Schwochau
Journal: Annals of the Rheumatic Diseases (1991)

Identification of several autoantibodies in serum samples from patients with ankylosing spondylitis or suspected ankylosing spondylitis is reported. Five antibodies associated with ankylosing spondylitis were identified by applying cytoimmunofluorescence and immunoblotting techniques to antigen pools from insect tissue. At least one of these antibodies was found in 82% of serum samples from patients with ankylosing spondylitis. A 36 kD drosophila antigen, which showed the most common and most dominant reaction, was further purified and isolated. Thirty two (34%) of the serum samples from 95 patients with definite ankylosing spondylitis and 12 (28%) of the serum samples from 43 patients with suspected ankylosing spondylitis reacted with this antigen. Antibodies purified from the 36 kD antigen reacted specifically with a 69 kD antigen present in separations of total protein preparations from human lymphocytes and HeLa cells. The 36 kD antibody was not found in 29 patients with rheumatoid arthritis nor in 38 apparently healthy controls. The prevalence of the 36 kD antibody was comparable in HLA-B27 positive and negative patients. In addition, the same immunoreaction was found in patients with so called 'seronegative' spondylarthropathies, particularly of the ankylosing spondylitis-type, suggesting that this antibody is specific for ankylosing spondylitis or other 'seronegative' spondylarthropathies with the typical clinical and radiological changes of ankylosing spondylitis.
Elevated circulating levels of heat shock protein 70 are related to systemic inflammatory reaction through monocyte Toll signal in patients with heart failure after acute myocardial infarction
Authors: Mamoru Satoh, Yudai Shimoda, Tomonari Akatsu, Yuh Ishikawa, Yoshitaka Minami, Motoyuki Nakamura
Journal: European Journal of Heart Failure (2006)
New Strategies in Radiation Therapy: Exploiting the Full Potential of Protons
Authors: Radhe Mohan, Anita Mahajan, Bruce D. Minsky
Journal: Clinical Cancer Research (2013)

Abstract Protons provide significant dosimetric advantages compared with photons because of their unique depth–dose distribution characteristics. However, they are more sensitive to the effects of intra- and intertreatment fraction anatomic variations and uncertainties in treatment setup. Furthermore, in the current practice of proton therapy, the biologic effectiveness of protons relative to photons is assumed to have a generic fixed value of 1.1. However, this is a simplification, and it is likely higher in different portions of the proton beam. Current clinical practice and trials have not fully exploited the unique physical and biologic properties of protons. Intensity-modulated proton therapy, with its ability to manipulate energies (in addition to intensities), provides an entirely new dimension, which, with ongoing research, has considerable potential to increase the therapeutic ratio. Clin Cancer Res; 19(23); 6338–43. ©2013 AACR.
Mortality associated with tiotropium mist inhaler in patients with chronic obstructive pulmonary disease: systematic review and meta-analysis of randomised controlled trials
Authors: S. Singh, Y. K. Loke, P. L. Enright, C. D. Furberg
Journal: BMJ (2011)

<b>Objective</b> To systematically review the risk of mortality associated with long term use of tiotropium delivered using a mist inhaler for symptomatic improvement in chronic obstructive pulmonary disease. <b>Data sources</b> Medline, Embase, the pharmaceutical company clinical trials register, the US Food and Drug Administration website, and ClinicalTrials.gov for randomised controlled trials from inception to July 2010. <b>Study selection</b> Trials were selected for inclusion if they were parallel group randomised controlled trials of tiotropium solution using a mist inhaler (Respimat Soft Mist Inhaler, Boehringer Ingelheim) versus placebo for chronic obstructive pulmonary disease; the treatment duration was more than 30 days, and they reported data on mortality. Relative risks of all cause mortality were estimated using a fixed effect meta-analysis, and heterogeneity was assessed with the I<sup>2</sup> statistic. <b>Results</b> Five randomised controlled trials were eligible for inclusion. Tiotropium mist inhaler was associated with a significantly increased risk of mortality (90/3686 <i>v</i> 47/2836; relative risk 1.52, 95% confidence interval, 1.06 to 2.16; P=0.02; I<sup>2</sup>=0%). Both 10 µg (2.15, 1.03 to 4.51; P=0.04; I<sup>2</sup>=9%) and 5 µg (1.46, 1.01 to 2.10; P=0.04; I<sup>2</sup>=0%) doses of tiotropium mist inhaler were associated with an increased risk of mortality. The overall estimates were not substantially changed by sensitivity analysis of the fixed effect analysis of the five trials combined using the random effects model (1.45, 1.02 to 2.07; P=0.04), limiting the analysis to three trials of one year's duration each (1.50, 1.05 to 2.15), or the inclusion of additional data on tiotropium mist inhaler from another investigational drug programme (1.42, 1.01 to 2.00). The number needed to treat for a year with the 5 µg dose to see one additional death was estimated to be 124 (95% confidence interval 52 to 5682) based on the average control event rate from the long term trials. <b>Conclusions</b> This meta-analysis explains safety concerns by regulatory agencies and indicates a 52% increased risk of mortality associated with tiotropium mist inhaler in patients with chronic obstructive pulmonary disease.
AT-44 * RELEARNING NEURO-ONCOLOGY: BAYES' THEOREM PROVIDES A NEW WORLD ORDER
Authors: A. Patel, J. Sheehan, M. Glantz
Journal: Neuro-Oncology (2014)

INTRODUCTION: All clinicians are Bayesian theoreticians, and implicitly use this calculus to make all treatment decisions . We explicitly applied Bayes' theorem to the most compelling randomized controlled trials (RCTs) in the field of neuro-oncology and discovered that our most widely accepted paradigms are incorrect. METHODS: We analyzed all high quality RCTs addressing: 1.) extent of resection for high-grade glioma; 2). Stupp regimen for newly diagnosed GBM; 3.) upfront bevacizumab for GBM; 4.) anticonvulsant prophylaxis for brain tumors; 5.) PCI in non-small cell lung cancer; and 6.) radiation at the time of diagnosis of low grade glioma. We applied Bayesian logic to trials sequentially in the order that they were published assuming various initial convictions ranging from "true believer" to "confirmed skeptic" with respect to belief in the current paradigm. We also calculated the characteristics of a RCT that would be required to change a clinician's mind. RESULTS: Bayesian analysis of the literature shows that clinicians should reasonably have a very strong conviction in favor of aggressive resection (despite flawed trials); Stupp regimen (despite only one RCT); and bevacizumab treatment at diagnosis (despite two conflicting RCTs). The study size, significance and power required to change a clinician's mind about these questions are nearly unattainable. Despite five RCTs, no clinicians' minds should be changed regarding anticonvulsant prophylaxis. Changing a skeptic to an advocate of prophylaxis with a new RCT should be easy. CONCLUSION: Explicit and unbiased application of Bayes' theorem to the most compelling studies in the field of neuro-oncology reveals profound flaws in our understanding of the most cherished tenants of neuro-oncology patient care.