tbuckley/cabot-search huggingface dataset:
Reversal of microRNA-150 silencing disadvantages crizotinib-resistant NPM-ALK(+) cell growth
Authors: Coralie Hoareau-Aveilla, Thibaud Valentin, Camille Daugrois, Cathy Quelen, Géraldine Mitou, Samuel Quentin, Jinsong Jia, Salvatore Spicuglia, Pierre Ferrier, Monica Ceccon, Sylvie Giuriato, Carlo Gambacorti-Passerini, Pierre Brousset, Laurence Lamant, Fabienne Meggetto
Journal: Journal of Clinical Investigation (2015)

The regulatory microRNA miR-150 is involved in the development of hemopathies and is downregulated in T-lymphomas, such as anaplastic large-cell lymphoma (ALCL) tumors. ALCL is defined by the presence or absence of translocations that activate the anaplastic lymphoma kinase (ALK), with nucleophosmin-ALK (NPM-ALK) fusions being the most common. Here, we compared samples of primary NPM-ALK(+) and NPM-ALK(–) ALCL to investigate the role of miR-150 downstream of NPM-ALK. Methylation of the MIR150 gene was substantially elevated in NPM-ALK(+) biopsies and correlated with reduced miR-150 expression. In NPM-ALK(+) cell lines, DNA hypermethylation–mediated miR-150 repression required ALK-dependent pathways, as ALK inhibition restored miR-150 expression. Moreover, epigenetic silencing of miR-150 was due to the activation of STAT3, a major downstream substrate of NPM-ALK, in cooperation with DNA methyltransferase 1 (DNMT1). Accordingly, miR-150 repression was turned off following treatment with the DNMT inhibitor, decitabine. In murine NPM-ALK(+) xenograft models, miR-150 upregulation induced antineoplastic activity. Treatment of crizotinib-resistant NPM-ALK(+) KARPAS-299-CR06 cells with decitabine or ectopic miR-150 expression reduced viability and growth. Altogether, our results suggest that hypomethylating drugs, alone or in combination with other agents, may benefit ALK(+) patients harboring tumors resistant to crizotinib and other anti-ALK tyrosine kinase inhibitors (TKIs). Moreover, these results support further work on miR-150 in these and other ALK(+) malignancies.
Germ-line BRCA1 mutations in women with sporadic breast cancer: clinical correlations.
Authors: E Garcia-Patiño, B Gomendio, M Provencio, J M Silva, J M Garcia, P España, F Bonilla
Journal: Journal of Clinical Oncology (1998)

PURPOSE Sporadic nonhereditary breast cancer is recognized as the most common form of this malignancy. Presence of germ-line mutations in the BRCA1 gene of these tumors is an infrequent event. We undertook the present study to evaluate the prevalence of germ-line mutations in patients diagnosed with sporadic breast cancer, and to delimit the clinical spectrum of this subgroup of patients with germ-line mutations and their differences with respect to patients with no evidence of BRCA1 gene mutations. METHODS We studied 105 patients diagnosed with breast cancer, selected from among our living patients; those with carcinoma-in-situ and those with a definite family history of breast or ovarian cancer were excluded. Genomic DNA, obtained from peripheral-blood lymphocytes, was studied for BRCA1 mutations by polymerase chain reaction/single-strand conformation polymorphism (PCR-SSCP) and direct DNA sequencing. Fourteen clinicopathologic parameters were analyzed in each patient. RESULTS Six (5.7%) frameshift mutations that corresponded to truncating proteins and three missense mutations, the functional meaning of which remains speculative, were identified. The patients with germ-line mutations were found to have a more advanced age at diagnosis, as well as a longer median survival (51 months). CONCLUSION Women with sporadic breast cancer of late onset may display a significant incidence of germline BRCA1 mutations, which occur at a rate not previously determined in this group of patients. The presence of variations in the sequence of the BRCA1 gene could influence the longer survival observed in these patients.
Development of an ASAS-endorsed recommendation for the early referral of patients with a suspicion of axial spondyloarthritis
Authors: Denis Poddubnyy, Astrid van Tubergen, Robert Landewé, Joachim Sieper, Désirée van der Heijde
Journal: Annals of the Rheumatic Diseases (2015)

The aim of this work was to develop a consensual recommendation under the auspices of the Assessment of SpondyloArthritis international Society (ASAS) for early referral of patients with a suspicion of axial spondyloarthritis by non-rheumatologists. The development of a referral recommendation consisted of four phases: (1) systematic literature review, (2) the first Delphi round aiming at identification of unmet needs and development of a candidate list of referral parameters, (3) the second Delphi round aiming at identification of the most useful combination of referral parameters and (4) final discussion and formal endorsement by ASAS membership. The following consensus on a referral recommendation was achieved as a result of the Delphi processes and final voting: "Patients with chronic back pain (duration ≥3 months) and back pain onset before 45 years of age should be referred to a rheumatologist if at least one of the following parameters is present: Inflammatory back pain; human leucocyte antigen-B27; Sacroiliitis on imaging if available (X-rays or magnetic resonance imaging); Peripheral manifestations (arthritis, enthesitis, dactylitis); Extra-articular manifestations (psoriasis, inflammatory bowel disease, uveitis); Positive family history for spondyloarthritis; Good response to non-steroidal anti-inflammatory drugs; Elevated acute phase reactant." A consensual ASAS-endorsed referral recommendation for patients suspected of having axial spondyloarthritis was developed as a flexible and universal strategy to be used in clinical practice by primary care physicians or non-rheumatology specialists. The practical value of this strategy applied in different settings should be determined in future studies.
Peptide insertions in reverse transcriptase pol gene of human immunodeficiency virus type 1 as a rare cause of persistent antiretroviral therapeutic failure
Authors: Véronique Schneider, Jérôme Legoff, Laurent Bélec, Nathalie Delphin, Corinne Dutreuil, Ali Kara-Mostefa, Willy Rozenbaum, Jean-Claude Nicolas
Journal: Clinical Microbiology and Infection (2004)
Prognostic Factors for Children and Adolescents With Surgically Resected Nonrhabdomyosarcoma Soft Tissue Sarcoma: An Analysis of 121 Patients Treated at St Jude Children's Research Hospital
Authors: Sheri L. Spunt, Catherine A. Poquette, Yasmeen S. Hurt, Alvida M. Cain, Bhaskar N. Rao, Thomas E. Merchant, Jesse J. Jenkins, Victor M. Santana, Charles B. Pratt, Alberto S. Pappo
Journal: Journal of Clinical Oncology (1999)

PURPOSE: The rarity and heterogeneity of pediatric nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) has precluded meaningful analysis of prognostic factors associated with surgically resected disease. To define a population of patients at high risk of treatment failure who might benefit from adjuvant therapies, we evaluated the relationship between various clinicopathologic factors and clinical outcome of children and adolescents with resected NRSTS over a 27-year period at our institution. PATIENTS AND METHODS: We analyzed the records of 121 consecutive patients with NRSTS who underwent surgical resection between August 1969 and December 1996. Demographic data, tumor characteristics, treatment, and outcomes were recorded. Univariate and multivariate analyses of prognostic factors for survival, event-free survival (EFS), and local and distant recurrence were performed. RESULTS: At a median follow-up of 9.2 years, 5-year survival and EFS rates for the entire cohort were 89% ± 3% and 77% ± 4%, respectively. In univariate models, positive surgical margins (P = .004), tumor size ≥ 5 cm (P &lt; .001), invasiveness (P = .002), high grade (P = .028), and intra-abdominal primary tumor site (P = .055) adversely affected EFS. All of these factors except invasiveness remained prognostic of EFS and survival in multivariate models. Positive surgical margins (P = .003), intra-abdominal primary tumor site (P = .028), and the omission of radiation therapy (P = .043) predicted local recurrence, whereas tumor size ≥ 5 cm (P &lt; .001), invasiveness (P &lt; .001), and high grade (P = .004) predicted distant recurrence. CONCLUSION: In this largest single-institution analysis of pediatric patients with surgically resected NRSTS, we identified clinicopathologic features predictive of poor outcome. These variables should be prospectively evaluated as risk-adapted therapies are developed.
A hepatic stellate cell gene expression signature associated with outcomes in hepatitis C cirrhosis and hepatocellular carcinoma after curative resection
Authors: David Y Zhang, Nicolas Goossens, Jinsheng Guo, Ming-Chao Tsai, Hsin-I Chou, Civan Altunkaynak, Angelo Sangiovanni, Massimo Iavarone, Massomo Colombo, Masahiro Kobayashi, Hiromitsu Kumada, Augusto Villanueva, Josep M Llovet, Yujin Hoshida, Scott L Friedman
Journal: Gut (2015)

<h3>Objective</h3> We used an informatics approach to identify and validate genes whose expression is unique to hepatic stellate cells and assessed the prognostic capability of their expression in cirrhosis. <h3>Design</h3> We defined a hepatic stellate cell gene signature by comparing stellate, immune and hepatic transcriptome profiles. We then created a prognostic index using a combination of hepatic stellate cell signature expression and clinical variables. This signature was derived in a retrospective–prospective cohort of hepatitis C-related early-stage cirrhosis (prognostic index derivation set) and validated in an independent retrospective cohort of patients with postresection hepatocellular carcinoma (HCC). We then examined the association between hepatic stellate cell signature expression and decompensation, HCC development, progression of Child–Pugh class and survival. <h3>Results</h3> The 122-gene hepatic stellate cell signature consists of genes encoding extracellular matrix proteins and developmental factors and correlates with the extent of fibrosis in human, mouse and rat datasets. Importantly, association of clinical prognostic variables with overall survival was improved by adding the signature; we used these results to define a prognostic index in the derivation set. In the validation set, the same prognostic index was associated with overall survival. The prognostic index was associated with decompensation, HCC and progression of Child–Pugh class in the derivation set, and HCC recurrence in the validation set. <h3>Conclusions</h3> This work highlights the unique transcriptional niche of stellate cells, and identifies potential stellate cell targets for tracking, targeting and isolation. Hepatic stellate cell signature expression may identify patients with HCV cirrhosis or postresection HCC with poor prognosis.
Differences Between Early and Late Readmissions Among Patients
Authors: Ronald L. Hirsch
Journal: Annals of Internal Medicine (2015)

Letters20 October 2015Differences Between Early and Late Readmissions Among PatientsRonald L. Hirsch, MDRonald L. Hirsch, MDFrom Accretive Health, Chicago, Illinois.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L15-5149 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Graham and colleagues (1) found that early readmissions were associated with markers of acute illness burden and late readmissions were associated with markers of chronic disease burden; they conclude that the time frame of 30 days after hospital discharge may not be homogeneous. As the authors note, the 30-day time frame used by the Centers for Medicare & Medicaid Services for their readmission reduction program probably penalizes hospitals for factors beyond their control and a narrower window is warranted.Graham and colleagues performed a sensitivity analysis at a 5-day cut point; when they found no significant difference, ...Reference1. Graham KL, Wilker EH, Howell MD, Davis RB, Marcantonio ER. Differences between early and late readmissions among patients: a cohort study. Ann Intern Med. 2015;162:741-9. [PMID: 26030632] doi:10.7326/M14-2159 LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From Accretive Health, Chicago, Illinois.Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterest Forms.do?msNum=L15-0400. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoDifferences Between Early and Late Readmissions Among Patients Kelly L. Graham , Elissa H. Wilker , Michael D. Howell , Roger B. Davis , and Edward R. Marcantonio Differences Between Early and Late Readmissions Among Patients Kelly L. Graham and Edward R. Marcantonio Differences Between Early and Late Readmissions Among Patients Kelly L. Graham and Edward R. Marcantonio Metrics 20 October 2015Volume 163, Issue 8Page: 649-650KeywordsAntibioticsConflicts of interestDisclosureEndocarditisMedicarePneumoniaPyelonephritis ePublished: 20 October 2015 Issue Published: 20 October 2015 Copyright & PermissionsCopyright © 2015 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Acetazolamide improves cardiac dysrhythmias in patients with obstructive sleep apnea at altitude. A randomized controlled trial
Authors: Tsogyal D. Latshang, Yvonne Nussbaumer-Ochsner, Barbara Kaufmann, Silvia Ulrich-Somaini, Malcolm Kohler, Robert Thurnheer, Ivan Fauchère, Ardan M. Saguner, Frank Scherff, Firat Duru, Konrad E. Bloch
Journal: European Respiratory Journal (2012)

Background: Untreated lowlanders with obstructive sleep apnea syndrome (OSA) benefit from acetazolamide (AC) during an altitude stay in terms of improved nocturnal oxygenation, breathing disturbances and sleep quality (Nussbaumer-Ochsner, Chest 2012). The current study evaluates whether AC reduces the increased rate of cardiac dysrhythmias at altitude.

Methods: 43 OSA patients living at <600m discontinued CPAP 3 days before baseline examination at 490m and during 2 altitude sojourns at 1860-2590m for 3 days each, one on AC 2x250mg/d, the other on placebo, according to a randomized cross-over design. Holter ECG and polysomnography were performed at 490m and at altitude.

Results: At altitude on placebo, heart rate was higher and dysrhythmias were more prevalent than at 490m. AC reduced bradycardia events, apneas/hypopneas and improved oxygen saturation [table].

Conclusions: The increased heart rate and the higher prevalence of dysrhythmias at altitude are consistent with increased sympathetic tone associated with hypoxemia. AC reduces bradycardia events at altitude, possibly by improving sleep disordered breathing.

View this table:

Dysrhythmias, oxygen saturation and breathing disturbances





Grants: Swiss National Science Foundation; Lung League of Zurich; Clinical Trials Center, University Hospital of Zurich, Switzerland.
Statistical Prediction Models, Artificial Neural Networks, and the Sophism “I Am a Patient, Not a Statistic”
Authors: Michael Kattan
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.2002.20.4.885 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11844805 Statistical Prediction Models, Artificial Neural Networks, and the Sophism "I Am a Patient, Not a Statistic" Michael KattanxMichael KattanSearch for articles by this author Show More Memorial Sloan-Kettering Cancer Center, New York, NY https://doi.org/10.1200/JCO.2002.20.4.885 First Page Full Text PDF Figures and Tables © 2002 by American Society of Clinical Oncology
Ga-67 scintigraphic findings in a case of multicentric reticulohistiocytosis.
Authors: KAZUYOSHI SUGA, NOBUHIKO OGASAWARA, KAZUMI MOTOYAMA, AKIKO HARA, NAOFUMI MATSUNAGA, TAKEHIKO MUTO
Journal: Clinical Nuclear Medicine (2002)

KAZUYOSHI, SUGA M.D.; NOBUHIKO, OGASAWARA M.D.; KAZUMI, MOTOYAMA M.D.; AKIKO, HARA M.D.; NAOFUMI, MATSUNAGA M.D.; TAKEHIKO, MUTO M.D. Author Information
Phase Ib/Ii, Multicenter, Single-Arm Trial of the Oral C-Met Inhibitor Msc2156119J As Monotherapy in Patients with Met-Positive Advanced Hepatocellular Carcinoma with Child-Pugh Class a Liver Function Who Failed Sorafenib Treatment
Authors: S. Faivre, B. Sarholz, A. Johne, H. Zheng, E. Raymond
Journal: Annals of Oncology (2014)
Low prevalence of Helicobacteraceae in gall-stone disease and gall-bladder carcinoma in the German population
Authors: U.R.M. Bohr, D. Kuester, F. Meyer, T. Wex, M. Stillert, A. Csepregi, H. Lippert, A. Roessner, P. Malfertheiner
Journal: Clinical Microbiology and Infection (2007)
Phase I/II study of the combination of carboplatin and paclitaxel as first-line chemotherapy in patients with advanced epithelial ovarian cancer
Authors: A. du Bois, H.-J. Lück, T. Bauknecht, V. Möbus, H. Bochtler, K. Diergarten, H.-G. Meerpohi
Journal: Annals of Oncology (1997)
Treatment of T-cell prolymphocytic leukemia with human CD52 antibody.
Authors: R Pawson, M J Dyer, R Barge, E Matutes, P D Thornton, E Emmett, J C Kluin-Nelemans, W E Fibbe, R Willemze, D Catovsky
Journal: Journal of Clinical Oncology (1997)

T-prolymphocytic leukemia (T-PLL) is an aggressive malignancy of mature T cells refractory to conventional chemotherapy, with a median survival duration of 7.5 months. We report here promising results with the use of a genetically reshaped human CD52 antibody, CAMPATH-1H.Fifteen patients with T-PLL, most of whom had received the purine analog deoxycoformycin (DCF), were treated with CAMPATH-1H. Results were compared with those of 25 patients treated with DCF.Major responses occurred in 11 patients (73%) treated with CAMPATH-1H compared with 40% with DCF. Complete remissions (CRs) were documented in nine (60%) of the CAMPATH-1H cases and only three (12%) were obtained with DCF. CRs with CAMPATH-1H were durable, and re-treatment with the antibody resulted in second CRs in three relapsed patients. Two of them were successfully autografted with peripheral-blood and bone marrow stem cells collected during the first CR. Apart from first-dose reactions, infusions of CAMPATH-1H were well tolerated. However, two responding patients developed severe bone marrow aplasia that was fatal in one; the second remained moderately pancytopenic 21 weeks after stopping CAMPATH-1H therapy. The cause of this adverse effect is unknown.CAMPATH-1H is an effective agent in T-PLL and represents a significant improvement over other types of therapy. However, CAMPATH-1H alone is not sufficient for long-term remissions, and the role of autologous stem-cell transplantation needs further investigation.
From mice to humans: developments in cancer immunoediting
Authors: Michele W.L. Teng, Jerome Galon, Wolf-Herman Fridman, Mark J. Smyth
Journal: Journal of Clinical Investigation (2015)

Cancer immunoediting explains the dual role by which the immune system can both suppress and/or promote tumor growth. Although cancer immunoediting was first demonstrated using mouse models of cancer, strong evidence that it occurs in human cancers is now accumulating. In particular, the importance of CD8+ T cells in cancer immunoediting has been shown, and more broadly in those tumors with an adaptive immune resistance phenotype. This Review describes the characteristics of the adaptive immune resistance tumor microenvironment and discusses data obtained in mouse and human settings. The role of other immune cells and factors influencing the effector function of tumor-specific CD8+ T cells is covered. We also discuss the temporal occurrence of cancer immunoediting in metastases and whether it differs from immunoediting in the primary tumor of origin.
Possible Role of Riboflavin Deficiency in Epithelial Neoplasia. III. Induction of Microsomal Aryl Hydrocarbon Hydroxylase&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: P. C. Chan, T. Okamoto, E. L. Wynder
Journal: JNCI Journal of the National Cancer Institute (1972)

In the skin and liver of mice fed a riboflavin-deficient diet for 4 weeks, the activity of aryl hydrocarbon hydroxylase (AHH) was lower than that in mice fed a riboflavin-supplemented diet. On riboflavin supplementation, either by injection or feeding, the activity of the AHH in the riboflavin-deficient mice was increased above that in mice fed the control diet. The dimethylbenz[a]anthracene (DMBA) induction of skin AHH in the deficient mice given riboflavin was also higher than that in mice fed the control diet and receiving riboflavin. However, the induction of hepatic AHH was retarded in the deficient mice receiving riboflavin intraperitoneally and DMBA topically.
Pulmonary Langerhans' cell histiocytosis (PLCH): A new UK register
Authors: Rebecca Mason, Noeleen Foley, Howard Branley, Toby Maher, Martin Hetzel, Huzaifa Adamali, Jay Suntharalingam
Journal: European Respiratory Journal (2012)

Introduction:  PLCH is a rare interstitial lung disease, linked to cigarette smoking and may be associated with respiratory failure and death. Limited UK data has been published and little knowledge exists of the diagnostic and treatment practices employed by UK physicians.   Aims and Objectives:  Our study aims to characterise the epidemiological, clinical, histological, radiological and prognostic indicators in a UK cohort of patients with PLCH.   Methods:  112 cases from 53 centres (65 from the BTS British Orphan Lung Disease database and 47 new or previously unregistered). Consultants provided contact details; Patients were sent an information leaflet, consent form and questionnaire. Once consent obtained, consultants were sent a medical questionnaire. The patients9 GP provided current medication and medical history.   Results:  Details on 95 patients (19 deceased, 7 lost to follow-up) received. Clinical information regarding 67 cases has been received; completed by the patient, consultant or both (31 males). Age at presentation 37.1 years (SD 14.4). Presenting symptoms: Dyspnoea 78%, cough 63%, constitutional symptoms 25%, pain 22% and pneumothorax 8%, Smoking status: Ex 71.7%, current 25.0% mean (SD) 19.9 (16.9) pack years. Cannabis use 9.6% Diagnosis: 93.8% patients had had an HRCT scan and 61% an open lung biopsy. Disease course: Symptoms resolved 23.3%, same 33.3% and 43.3% had slowly progressed. Treatment: None 56%, Steroids 29.6% immunosuppression/chemotherapy 26.5%. pleural surgery 18.7% and lung transplant 6%   Conclusions:  This UK dataset indicates a high prevalence of smoking in our cohort and, despite advances in computed tomography a high percentage of patients are still diagnosed with an open lung biopsy.
Immunotherapy in Bee Sting Hypersensitivity
Authors: U. Müller, U. Thurnheer, R. Patrizzi, J. Spies, R. Hoigné
Journal: Allergy (1979)

Fifty‐six patients with serologically confirmed bee sting hypersensitivity were treated for 1–3 years with either bee venom (BV) (31 patients) or wholebody extract (WBE) (25 patients). Twelve patients in each group were re‐exposed to a bee sting. Twenty‐five per cent of re‐exposed patients on BV‐therapy showed a diminished reaction and 75% no reaction. Thirty‐three per cent of re‐exposed patients on WBE‐therapy developed an unchanged or worse reaction, 42% a diminished reaction and 25% no reaction at all. An initial rise in BV‐specific IgE was observed in BV‐treated patients, whereas IgE levels after 1 year of treatment lay significantly below pretreatment values in both treatment groups. BV‐specific IgG increased markedly in patients on BV‐therapy and decreased slightly in those on WBE‐therapy. The initial IgE increase induced by BV‐therapy was insignificant in patients with high pretreatment levels of specific IgG‐antibodies. Similarly, re‐exposed patients with high BV‐specific IgG showed no IgE increase, whereas a substantial rise in specific IgE was observed in those with low IgG. On the basis of clinical and serological results immunotherapy with BV is considered to be clearly superior to immunotherapy with WBE