tbuckley/cabot-search huggingface dataset:
Clinical characteristics and outcomes associated with <i>BRAF</i> and <i>NRAS</i> mutations in metastatic melanoma.
Authors: J. A. Jakob, R. L. Bassett, C. S. Ng, A. J. F. Lazar, G. C. Alvarado, M. L. Rohlfs, J. Richard, J. E. Gershenwald, P. Hwu, K. B. Kim, M. A. Davies
Journal: Journal of Clinical Oncology (2011)

8500 Background: BRAF and NRAS are frequently mutated in melanoma. We performed a retrospective chart review of patients (pts) to identify clinical characteristics and outcomes associated with tumor mutation status. Methods: We identified pts (n=677) treated at the MD Anderson Cancer Center (MDACC) with testing for both BRAF (exon 15) and NRAS (codons 12, 13, and 61) mutations by the MDACC Molecular Pathology Lab from 2/07 to 9/10. Clinicopathologic characteristics, vital status, and the incidence, timing, and sites of distant metastasis were reviewed. Two- and three-group comparisons were performed to determine characteristics and outcomes significantly associated with BRAF, NRAS, and wild-type (WT) genotypes. Results: Overall, 47% of pts had a BRAF mutation, 20% NRAS, and 33% were WT. Pts with a BRAF mutation were diagnosed at a younger age than NRAS or WT pts (p<0.001). As the majority of mutation testing was performed for advanced disease, we focused our analysis on pts who developed stage IV disease (n=519). There was no significant difference by mutation status in the interval from original diagnosis, serum LDH, or M stage at diagnosis of stage IV. Mutation status did correlate with CNS involvement at diagnosis of stage IV (p=0.008): CNS metastases in 24% of BRAF, 23% of NRAS, and 12% of WT pts (p=0.01 vs BRAF, p=0.056 vs NRAS). In contrast, mutation status did not correlate with involvement of bone (p=0.43), liver (p=0.79), or other non-pulmonary visceral organs (p=0.77) at stage IV diagnosis. Mutation status was also associated with overall survival (OS) from the diagnosis of stage IV disease (p=0.02). NRAS pts had shorter median OS (1.3 yrs) than WT (2.0 yrs, p=0.03) or BRAF (1.9 yrs, p=0.03) pts. Conclusions: This study describes one of the largest cohorts of melanoma pts characterized for BRAF and NRAS mutations, and identifies new significant clinical associations in patients with stage IV disease. These findings support the need for additional analyses of the relationship between BRAF and NRAS mutations and clinical outcomes in advanced melanoma patients, to help guide patient management and appropriate clinical trial design. The data also highlight the need for more effective therapies for NRAS-mutant melanoma.
Historic air pollution exposure and long-term mortality risks in England and Wales: prospective longitudinal cohort study
Authors: Anna Hansell, Rebecca E Ghosh, Marta Blangiardo, Chloe Perkins, Danielle Vienneau, Kayoung Goffe, David Briggs, John Gulliver
Journal: Thorax (2016)

<h3>Introduction</h3> Long-term air pollution exposure contributes to mortality but there are few studies examining effects of very long-term (&gt;25 years) exposures. <h3>Methods</h3> This study investigated modelled air pollution concentrations at residence for 1971, 1981, 1991 (black smoke (BS) and SO<sub>2</sub>) and 2001 (PM<sub>10</sub>) in relation to mortality up to 2009 in 367 658 members of the longitudinal survey, a 1% sample of the English Census. Outcomes were all-cause (excluding accidents), cardiovascular (CV) and respiratory mortality. <h3>Results</h3> BS and SO<sub>2</sub> exposures remained associated with mortality decades after exposure—BS exposure in 1971 was significantly associated with all-cause (OR 1.02 (95% CI 1.01 to 1.04)) and respiratory (OR 1.05 (95% CI 1.01 to 1.09)) mortality in 2002–2009 (ORs expressed per 10 μg/m<sup>3</sup>). Largest effect sizes were seen for more recent exposures and for respiratory disease. PM<sub>10</sub> exposure in 2001 was associated with all outcomes in 2002–2009 with stronger associations for respiratory (OR 1.22 (95% CI 1.04 to 1.44)) than CV mortality (OR 1.12 (95% CI 1.01 to 1.25)). Adjusting PM<sub>10</sub> for past BS and SO<sub>2</sub> exposures in 1971, 1981 and 1991 reduced the all-cause OR to 1.16 (95% CI 1.07 to 1.26) while CV and respiratory associations lost significance, suggesting confounding by past air pollution exposure, but there was no evidence for effect modification. Limitations include limited information on confounding by smoking and exposure misclassification of historic exposures. <h3>Conclusions</h3> This large national study suggests that air pollution exposure has long-term effects on mortality that persist decades after exposure, and that historic air pollution exposures influence current estimates of associations between air pollution and mortality.
Abstract 13747: Diastolic Dysfunction Following Anthracycline-based Chemotherapy
Authors: José M Serrano, Silvia Del Castillo, Luis Javier Morales, Pedro Talavera, Carmen Cristobal, Iria Gonzalez, Juan Guerra, Carlos Gutierrez, Javier Muñiz, Joaquín J Alonso
Journal: Circulation (2013)

Background: As in other conditions diastolic dysfunction (DD) may precede systolic changes and may be an early manifestation of antraciclyne chemoteraphy cardiotoxicity. Data about the evolution of...
Heterogeneity of leukemia-initiating capacity of chronic myelogenous leukemia stem cells
Authors: Bin Zhang, Ling Li, Yinwei Ho, Min Li, Guido Marcucci, Wei Tong, Ravi Bhatia
Journal: Journal of Clinical Investigation (2016)

Chronic myelogenous leukemia (CML) results from transformation of a long-term hematopoietic stem cell (LTHSC) by expression of the BCR-ABL fusion gene. However, BCR-ABL-expressing LTHSCs are heterogeneous in their capacity as leukemic stem cells (LSCs). Although discrepancies in proliferative, self-renewal, and differentiation properties of normal LTHSCs are being increasingly recognized, the mechanisms underlying heterogeneity of leukemic LTHSCs are poorly understood. Using a CML mouse model, we identified gene expression differences between leukemic and nonleukemic LTHSCs. Expression of the thrombopoietin (THPO) receptor MPL was elevated in leukemic LTHSC populations. Compared with LTHSCs with low MPL expression, LTHSCs with high MPL expression showed enhanced JAK/STAT signaling and proliferation in response to THPO in vitro and increased leukemogenic capacity in vivo. Although both G0 and S phase subpopulations were increased in LTHSCs with high MPL expression, LSC capacity was restricted to quiescent cells. Inhibition of MPL expression in CML LTHSCs reduced THPO-induced JAK/STAT signaling and leukemogenic potential. These same phenotypes were also present in LTHSCs from patients with CML, and patient LTHSCs with high MPL expression had reduced sensitivity to BCR-ABL tyrosine kinase inhibitor treatment but increased sensitivity to JAK inhibitors. Together, our studies identify MPL expression levels as a key determinant of heterogeneous leukemia-initiating capacity and drug sensitivity of CML LTHSCs and suggest that high MPL-expressing CML stem cells are potential targets for therapy.
Quantification of smokers and smoking status among COPD patients, hospitalized for an exacerbation
Authors: Kasper Ankjærgaard, Torgny Wilcke, Hans-Jørgen Bendixen, Carsten Juhl
Journal: European Respiratory Journal (2011)

Background: In 2009, Dept of Pulmonary Medicine and Depts of Physiotherapy and Ergotherapy, Gentofte Hospital, University of Copenhagen have carried out the pilote study “KOL-hjem-igen” (COPD-home-again)  There are no official Danish data concerning smoking status or smoking history of COPD-patients, whom have been hospitalized due to an exacerbation  Methods: In a prospective uncontrolled pilot-study we included patients discharged after an exacerbation of COPD 1.1.2009 to 31.12.2009 in COPD-home-again. This consists of open telephone line, home visits by a COPD nurse 5-7 days and 6 months after discharge, individual self-care plan, rehabilitation by physiotherapist and ergotherapist during admission including self-training plan and visitation to rehabilitation.  All patients admitted with exacerbation of COPD were registered as for smoking status and -history. If still smoking at discharcge, the patients were offered smoking cessation assistance as a golden standard.  Results: 154 patients were included. Smoking data were registered on 126. 28 had died or were excluded. At inclusion 26 (20.6%) were smokers, 91 (72.3%) were ex smokers and 9 (7.1%) had never smoked. The average history of smoking was 38 package-years.  At 6 month follow up of 94 patients 22 (25%) were still smoking.  Mortality in still, former and never smokers were 22.7, 23.5 and 11% respectively.  Conclusions: Every fourth patient, that has been hospitalized due to an exacerbation still smokes six months after discharge. Interestingly, smoking status after exacerbation seems not to influence on mortality.  This is opposed to known data. Though, the study population is too small to make such conclusions.
A 6 years experience in Home-Care: Efficient and cost-effective strategy of treatment in terminal cancer care
Authors: M. Ranuzzi, G. Palmeri, D. Manzo, A. Corlito, A. Taddei, S. Brunetti, S. Gentile, R. Vercelloni
Journal: Journal of Clinical Oncology (2005)

8183 Background: The G.R.A.D.O. Association (Gruppo Ricerca Assistenza Domiciliare Oncologica) providing home-care for cancer patients was begun in June 1998. The drawing thought of our work is that, in the advanced phases of cancer, the best place of treatment should be the patients’ home, considering that house is the natural container of persons’ life which, with a convenient help, would prefer to spend the terminal phases of their life at home rather than hospital. Patients and Methods: Patients are visited at home by an oncologist and a professional nurse; they together draw up the assistance program. The professional teem is also composed of an internist, a physician for pain therapy, a psychologist, a physiotherapist. Assistance is completely free for the patients and their families. The professional team is also supported by a group of trained volunteers who are responsible for the social aspects of the patients’ life. During these six years of activity 455 patients, the mean age was 64.7 yrs (16–90), have been followed: they requested 3352 oncological visits, 991 medical visits, 25 chemotherapies, 288 thoracentesis, 292 paracentesis, 2538 nurse interventions, 2839 supportive treatments, 35 physiotherapeutic interventions and 661 psychological supports. The median follow up were 37 days (3–359). The 88% of the patients died at home. Conclusion: The data regarding our activity showed us that this specifically oriented medical assistance permits education and adaptation of patients and their families with the disease and diminishes the hospitalization of these patients, resulting in an improvement of their quality of life (better preserved in their family environment). During our years of activity we have distributed 31.439 days of medical services and it has certainly helped in saving the expenses of the welfare state. So considering the mean cost of a day in a general hospital approximately equivalent to 700,00$ and considering a day of medical services= a day of non-hospitalization, our work allowed an economical benefit of 22.007.300,00$ for the public health resources (3.667.883,33$/year). Home-Care models could be the successful instruments and strategies of treatment in advanced cancer care. No significant financial relationships to disclose.
간세포암종의 방사선치료 시 발생하는 간독성에대한 위험인자의 재고찰
Authors: 이익재 ( Ik Jae Lee ), 성진실 ( Jinsil Seong ), 심수정 ( Su Jung Shim ), 한광협 ( Kwang Hyub Han ), 전재윤 ( Chae Yoon Chon )
Journal: Clinical and Molecular Hepatology (2006)

Background/Aims: Determination of the optimal radiotherapeutic parameters for radiotherapy of hepatocellular carcinoma (HCC) is still under investigation. The purpose of this study is to identify the risk factors associated with radiation-related morbidity. Methods: We evaluated one hundred fifty-eight patients, who were given radiotherapy for HCC between January 1992 and March 2000. Radiation-induced liver disease (RILD) was defined as the development of nonmalignant ascites without disease progression and an anicteric elevation of the alkaline phosphatase level by at least twofold. Gastrointestinal toxicity was assessed by using the RTOG-EORTC scale. Results: Six patients (3.8%) displayed RILD. In these patients, three patients had not responded to other previous treatments. Two patients with portal vein thrombosis or huge sized mass, above 10 cm, showed liver toxicity and two other patients presented with Child-Pugh class B liver cirrhosis. Eight patients (5%) had gastro-duodenal ulcers. In one of these 8 patients, the left lobe close to the stomach was involved and two patients had been treated for gastro-duodenal ulcer. In two more patients, the radiation field, with using anterior/posterior radiation ports, covered a significant volume of the gastrointestinal tract. One of eight patients had been irradiated with a large fraction size (250 cGy). Conclusions: The efforts should be made to reduce the radiation-related complications for hepatocellular carcinoma by considering the volume and the function of remaining liver, the location of tumor, the tumor size and the severity of liver cirrhosis
HIF-1α Promotes Glutamine-Mediated Redox Homeostasis and Glycogen-Dependent Bioenergetics to Support Postimplantation Bone Cell Survival
Authors: Steve Stegen, Nick van Gastel, Guy Eelen, Bart Ghesquière, Flora D’Anna, Bernard Thienpont, Jermaine Goveia, Sophie Torrekens, Riet Van Looveren, Frank P. Luyten, Patrick H. Maxwell, Ben Wielockx, Diether Lambrechts, Sarah-Maria Fendt, Peter Carmeliet, Geert Carmeliet
Journal: Cell Metabolism (2016)
Autologous Antibodies Eluted From Membrane Fragments in Human Ovarian Epithelial Neoplastic Effusions. II. Tissue Specificity and Reactivity&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: W H Kutteh, G J Doellgast
Journal: JNCI Journal of the National Cancer Institute (1986)

Cyst and ascitic fluids from patients with ovarian epithelial neoplasms were studied to determine whether they contained immunoglobulins with antitumor activity. The results demonstrated the presence of autologous antibodies bound to the cellular membrane fragments obtained from human ovarian neoplastic effusions. Membrane fragments were prepared from more than 60 samples of human ovarian effusions, and the amounts of membrane-bound IgG and IgA were determined. Six fluids obtained from patients with malignant ovarian neoplasms were selected for large-scale preparation of IgG, on the basis of the quantity of fluid available (greater than 200 ml) and amount of membrane-bound IgG (greater than 400 ng/ml) determined by enzyme-linked immunoassay. The antibodies were strongly reactive with cell-surface antigens on 4 different human ovarian cell lines, 4 surgical specimens of human ovarian adenocarcinoma, and 2 human ovarian tumors grown in athymic BALB/c mice, as demonstrated by indirect immunofluorescence. The antibodies did not react, or reacted only weakly, with tissue preparations from 4 normal human ovaries, other nonovarian normal or neoplastic tissues, and nonovarian human cell lines. These studies indicate that patients with ovarian cancer have the capability to recognize and form antibodies against autologous ovarian tumor-associated antigens.
Abstract 12193: Phosphorylated Venous Endothelial Nitric Oxide Synthase is Elevated in Rheumatoid Arthritis Subjects With High Disease Activity
Authors: Elizabeth B Solow, Wanpen Vongpatanasin, David R Karp
Journal: Circulation (2013)

Introduction: Endothelial dysfunction is present in arthritis animal models and rheumatoid arthritis (RA), a population known to develop premature cardiovascular disease. Previous studies indicate ...
Bronchoalveolar lavage fluid recovery in children correlates with age and neutrophils
Authors: Marcus Svedberg, Karsten Kötz, Bill Hesselmar
Journal: European Respiratory Journal (2014)

Background. Bronchoalveolar lavage (BAL) is an important tool in the diagnostic evaluation of respiratory diseases in children. Very little has been reported about the BAL fluid recovery and its variation in children. In this study we investigated the relationship between BAL fluid recovery, age, gender and inflammatory pattern.  Method. A total of 311 children who underwent diagnostic bronchoscopy with BAL and BAL-cytology at Queen Silvia Children9s Hospital, Gothenburg, Sweden, during 2007 to 2013 were included in the study. 58% were boys and the median age was 6 years, (range 0.1 - 18 years). All bronchoscopies were performed during general anaesthesia. 333 BAL-procedures were performed, and the instilled BAL-volume was adjusted to the patient9s body weight, 3ml/kg, divided into three equal aliquots (maximum 3x50 ml).  Results. Mean BAL fluid recovery was 51% (SD 21%). A positive correlation was found between BAL fluid recovery and age (r = 0.43, p=0.000), and a negative correlation between BAL fluid recovery and BAL-neutrophils (r= -0.30, p=0.000), when controlling for BAL- neutrophils and age respectively. BAL fluid recovery was not affected by gender, or by the percentage of BAL-lymphocytes.  Conclusion. Young age, and a high percentage of BAL-neutrophils, are associated with a reduced BAL fluid recovery in children.
Is sleep deprivation useful in the treatment of depression?
Authors: E Leibenluft, T A Wehr
Journal: American Journal of Psychiatry (1992)

The authors critically reviewed the literature on clinical applications of sleep deprivation in the treatment of depression.They included all studies using sleep deprivation for clinical purposes, with the exception of treatment studies that did not provide follow-up beyond a night of recovery sleep. They focused on six uses of sleep deprivation: 1) to potentiate response to antidepressant medication (13 studies), 2) to hasten the onset of action of antidepressant medication or lithium (five studies), 3) to prevent recurrent mood cycles (four studies), 4) as an alternative to antidepressant medication (five studies), 5) as a diagnostic probe (two studies), and 6) to predict response to antidepressant medication (nine studies).Although the literature appears to demonstrate the efficacy of sleep deprivation as a potentiation strategy, these treatment studies have substantial methodological shortcomings. Well-designed pilot studies indicate that sleep deprivation may hasten the onset of action of thymoleptic medications. Sleep deprivation may prevent premenstrual mood swings, and response to sleep deprivation may differentiate depressive pseudodementia from primary degenerative dementia with depression. Studies attempting to use sleep deprivation to predict response to antidepressant medication have yielded inconsistent results.Given the noninvasive nature of sleep deprivation, it would be useful to determine if even a small subset of refractory patients respond to it. The authors suggest future research directions to determine the usefulness of this potential treatment.
Abstract 13466: Assessment of Myocardial and Microvascular Injury of Takotsubo cardiomyopathy and ST-elevation Myocardial Infarction by Cardiac Magnetic Resonance Imaging
Authors: Akiko Fujino, Teruo Noguchi, Masaharu Ishihara, Hiroki Sakamoto, Michio Nakanishi, Jun-ichi Kotani, Yasuhide Asaumi, Tadayoshi Miyagi, Tetsuo Arakawa, Taichi Adachi, Reon Kumasaka, Masafumi Yamane, Masashi Fujino, Yoichi Goto, Toshihisa Anzai, Wataru Shimizu, Satoshi Yasuda, Hisao Ogawa
Journal: Circulation (2012)

Background: Takotsubo cardiomyopathy (TC) is a novel cardiac condition characterized by distinctive regional left ventricular (LV) systolic dysfunction. Although acute LV systolic dysfunction as we...
Abstract 96: Thioredoxin-1 Is Essential for Hydrogen Sulfide-Mediated Cardioprotection in the Setting of Ischemic-Induced Heart Failure
Authors: Chad K Nicholson, Bridgette F Moody, Rebecca L Hood, Junichi Sadoshima, John W Calvert
Journal: Circulation Research (2012)

Background: Numerous studies have reported the cytoprotective effects of hydrogen sulfide (H2S) in various models of myocardial injury. Here we examined the role that thioredoxin-1 (Trx1) plays in mediating the protective effects of H2S in a model of heart failure. Methods and Results: Mice were subjected to 60 min of left coronary artery ischemia followed by 4 wks of reperfusion (R) at which time left ventricular dimensions and function were assessed. Mice received saline (Veh) or H2S in the form of sodium sulfide (Na2S, 100 μ g/kg) at the time of R followed by daily i.v. injections for the first 7 days of R. Mice treated with Na2S experienced less left ventricular dilatation and hypertrophy, displayed improved left ventricular ejection fraction, and displayed improved contractility and relaxation when compared to Veh-treated mice. Studies aimed at evaluating the underlying cardioprotective mechanisms found that Na2S treatment increased the expression of Trx1. Further analysis revealed that this was accompanied by an increase in phosphorylation of apoptosis signaling kinase-1 (ASK1) at serine residue 966 (inhibitory site), as well as a decrease in the phosphorylation of JNK and p38 (downstream targets of ASK1). We also found that Na2S treatment did not improve cardiac dilatation, cardiac dysfunction, or cardiac hypertrophy in cardiac specific Trx1 dominant negative transgenic (Trx1 dnTg) mice when compared to Veh-treated mice. Conclusion: These findings provide important information that the upregulation of cardiac Trx1 by H2S in the setting of ischemic-induced heart failure sets into motion events, including ASK1 inhibition, which ultimately leads to cardioprotection.
Novel mutations and mutation pattern of epidermal growth factor receptor (EGFR) gene in Chinese patients with primary lung adenocarcinoma
Authors: T. Mok, P. Lui, K. C. Lam, A. Yim, I. Wan, S. Lee, M. Hsin, L. Leung, K. To
Journal: Journal of Clinical Oncology (2007)

7667 Background: EGFR mutation is a diverse and complex phenomenon. Shigematsu et al (JNCI 97:339,2005), analyzing NSCLC samples from multiple ethnicities and histologic cell types, reported 11 types of in-frame deletions in exon 19 (46%), 9 missense mutation in exons 18, 20, 21 (45%) and 8 in-frame insertion in exons 20 (9%). 3/130 tumors (2.3%) had multiple mutations. Here we report the incidence, mutation pattern and novel finding of EGFR mutation in a homogenous ethnic group with adenocarcinoma of lung. Methods: Between 2004 and 2006 we isolated genomic DNA from 194 (archival 53, prospective 141) primary lung adenocarinoma for PCR amplification of EGFR exon 18–21. We isolated tumor cell by micro-dissection. PCR products were purified and sequenced using the BigDye Terminator Cycly Sequencing Ready Reaction Kit (Applied Biosystem) and run on Applied Biosystem 3100 Genetic Analyzer. Results: We found 79 EGFR mutations in 73 tumors (37.6%). Six (8.2%) had double mutations. IN-FRAME DEL: 10 types in exon 19 (39 cases, 49.4%); 1 type in exon 18 (1 case). MISSENSE MUTATION: 2 types in exon 18 (2 cases); 4 types in exon 20 (5 cases) and 2 types in exon 21 (29 cases, 36.7%) IN-FRAME INSERTION: 3 types in exon 20 (3 cases). Typical exon 19 E746-A750del and exon 21 L858R mutations accounted for 31% and 34%, respectively. We found 11 types of mutations not previously described.( Table ) Four pts with novel mutations received EGFR TKI and 3 attained PR (all with exon 19 del). Two pts have T790M mutations without prior exposure to EGFR TKI and both with double mutations. Conclusion: Mutation pattern of EGFR gene in Chinese pts with adenocarcinoma is similar to the Shigematsu report. The overall incidence of EGFR mutation and multiple mutations are higher but in-frame insertion in exon 20 is less common. Majority of the novel mutations are rare mutations involving exon 18 and 20. No significant financial relationships to disclose. [Table: see text]