tbuckley/cabot-search huggingface dataset:
Abstract P3-08-04: Aspirin and breast cancer risk for <i>BRCA1</i> and <i>BRCA2</i> mutation carriers
Authors: Naomi Kornhauser, Mary Beth Terry, Linda T Vahdat, Irene Andrulis, Saundra Buys, Mary Daly, Esther John, John L Hopper, Tessa Cigler
Journal: Cancer Research (2015)

Abstract Background : Although epidemiologic studies have found evidence that aspirin use may be inversely associated with breast cancer (BC) risk, little is known about whether this applies to BRCA1 and BRCA2 mutation carriers. Methods : We compared aspirin use in 613 women with BRCA1 or BRCA2 mutations from the six centers of the Breast Cancer Family Registry (BCFR) who were recruited at baseline and completed a questionnaire at 10 year follow-up. We defined cases as carriers with BC (n = 215 with BRCA1 mutations and 137 with BRCA2 mutations) and controls as carriers unaffected with BC (n = 141 with BRCA1 mutations and 120 with BRCA2 mutations). We used logistic regression to estimate odds ratios and 95% confidence intervals separately by gene mutation type. Results : Three cases (1.4%) and 27 controls (19.1%) among the BRCA1 carriers and 3 cases (2.2%) and 25 controls (20.8%) among the BRCA2 carriers reported ever use of aspirin-based medications before diagnosis. Aspirin use before diagnosis was inversely associated with BC risk for both BRCA1 (OR, 0.13; 95% CI, 0.04-0.46 for ever vs. never use) and BRCA2 (OR, 0.12; 95% CI, 0.03-0.41 for ever vs. never use) carriers, after adjusting for age and center for BRCA1 carriers and age for BRCA2 carriers. Conclusion : If replicated by larger, prospective studies, aspirin use could become an inexpensive and acceptable risk-reducing measure for BRCA1 and BRCA2 mutation carriers. Citation Format: Naomi Kornhauser, Mary Beth Terry, Linda T Vahdat, Irene Andrulis, Saundra Buys, Mary Daly, Esther John, John L Hopper, Tessa Cigler. Aspirin and breast cancer risk for BRCA1 and BRCA2 mutation carriers [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-08-04.
Defining low-dose corticosteroid: the pendulum still oscillates
Authors: Prasanta Raghab Mohapatra, Gourahari Pradhan, Priyadarshini Behera, Sourin Bhuniya, Manoj Kumar Panigrahi, Deepak Aggarwal
Journal: European Respiratory Journal (2015)

Tagami et al. [1], in their retrospective analysis, have contributed to further understanding of the use of corticosteroids in severe community-acquired pneumonia (CAP) and put forth an inference on the current dispute. Some issues, however, need further discussion. Defining low-dose corticosteroid in severe community-acquired pneumonia <http://ow.ly/OazzW>
Myeloid Growth Factors Guidelines
Authors: Jeffrey Crawford, Betsy Althaus, James Armitage, Douglas W. Blayney, Spero Cataland, David C. Dale, George D. Demetri, James Foran, Mark L. Heaney, Sally Htoy, Dwight D. Kloth, Gary H. Lyman, Laura Michaud, Susannah Motl, Saroj Vadhan-Raj, Michael K. Wong
Journal: Journal of the National Comprehensive Cancer Network (2007)

Chemotherapy-induced neutropenia can cause complications that result in dose reductions or treatment delays that can, in turn, compromise clinical outcomes. Although the prophylactic use of colony-stimulating factors (CSFs) can reduce the risk, severity, and duration of severe and febrile neutropenia, they are not routinely administered to all patients undergoing myelosuppressive chemotherapy because of the costs. Selective use may, however, enhance their cost-effectiveness. These guidelines discuss the preventative or prophylactic use of recombinant human granulocyte-CSF to reduce the incidence, length, and severity of chemotherapy-related neutropenia and and prevent life-threatening complications. For the most recent version of the guidelines, please visit NCCN.org
Challenges in the Diagnosis and Treatment of Homozygous Familial Hypercholesterolemia
Authors: Matthew K. Ito, Gerald F. Watts
Journal: Drugs (2015)

Homozygous familial hypercholesterolemia (HoFH) is a rare, genetic disorder characterized by an absence or impairment of low-density lipoprotein receptor (LDLR) function resulting in significantly elevated low-density lipoprotein cholesterol (LDL-C) levels. The cholesterol exposure burden beginning in utero greatly increases the risk for atherosclerotic cardiovascular disease (ASCVD) and premature death. The genetic heterogeneity of HoFH results in a wide range of LDL-C levels among both untreated and treated patients. Diagnosis of HoFH should, therefore, be based on a comprehensive evaluation of clinical criteria and not exclusively LDL-C levels. As treatment goals, the European Atherosclerosis Society and International FH Foundation suggest target LDL-C levels of <100 mg/dL (<2.5 mmol/L) in adults or <70 mg/dL (<1.8 mmol/L) in adults with clinical coronary artery disease or diabetes. The National Lipid Association (NLA) recommends that LDL-C levels be reduced to <100 mg/dL (<2.5 mmol/L) or by at least ≥50 % from pretreatment levels. Conventional therapy combinations that lower atherogenic lipoproteins levels in the blood, such as statins, ezetimibe, bile acid sequestrants and niacin, as well as lipoprotein apheresis, are usually unable to reduce LDL-C levels to recommended targets. Two recently approved agents that reduce lipoprotein synthesis and secretion by the liver are lomitapide, a microsomal triglyceride transfer protein inhibitor, and mipomersen, an apolipoprotein B antisense oligonucleotide. The newly approved inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9), evolocumab, also shows promise for the management of FH. Because of the extremely high risk for ASCVD, HoFH patients should be identified early.
The impact of a respiratory in-reach service into the emergency assessment unit (EAU) on treatment, length of stay, and re-admission rates
Authors: Fenella Johnstone, Lee Dowson
Journal: European Respiratory Journal (2011)

Background:  Respiratory illness is the second commonest reason for admission to hospital in the UK. Specialist input leads to better outcomes and reduced length of stay. Approximately half of respiratory patients, at New Cross Hospital, Wolverhampton, are not reviewed by a specialist during their admission.   Aims:  The aim of this study was to assess whether addition of specialist respiratory input into the EAU, would optimise patient management, and thus reduce length of stay and re-admission rates.   Methods:  During the weekday working hours, we piloted a twice daily respiratory ward round in the EAU. We audited management against current BTS guidance, altering treatment where necessary. We compared length of stay and re-admission rates during the pilot month to that of the preceding month. We collected data on whether patients would have been appropriate for referral to a respiratory “hot clinic”, to assess the need and demand for this service in the Wolverhampton City PCT.   Results:  73.1% of patients had management altered, according to BTS guidance. 53.7% of patients had underlying respiratory disease on admission, and of these, only 50% were optimally treated according to guidance. Re-admission rates decreased by 13.4% and length of stay decreased by 1.38 days. 25% of patients could have been seen in a “hot clinic”, preventing a hospital admission.   Conclusion:  There is a role for the addition of a respiratory specialist ward round in the EAU of New Cross Hospital, to optimise management of patients with respiratory illness, and to reduce patient length of stay and re-admission rates.
Phase I/II trial of everolimus in combination with bortezomib and rituximab (RVR) in relapsed/refractory Waldenstrom macroglobulinemia
Authors: I M Ghobrial, R Redd, P Armand, R Banwait, E Boswell, S Chuma, D Huynh, A Sacco, A M Roccaro, A Perilla-Glen, K Noonan, M MacNabb, H Leblebjian, D Warren, P Henrick, J J Castillo, P G Richardson, J Matous, E Weller, S P Treon
Journal: Leukemia (2015)
Confine yourself to forms of English that are easily understood
Authors: J. Kirkman
Journal: BMJ (1996)

trust's year on year change in its index value.Depending on how the national cost weights and trusts' activity change from year to year, it is theoretically possible for an individual trust's index to go down (relative to other trusts) even though their actual productivity has gone up (compared with their own value of the previous year).A useless statistic?Many of these criticisms are acknowledged by the NHS Executive,' which notes that many other factors need to be taken into account when interpreting and acting on the information, provided by the labour productivity index.For example, leaving aside the particular problems with the index, is it measuring what would be useful to measure?Should a trust be considered "productive"-that is, having a high index value-if the activity its employees are producing is inappropriate or ineffective?The obvious question, however, is whether the interpretative difficulties of the labour productivity index are so great as to render it useless for the job it is designed to do (presumably increasing labour productivity in the NHS). ConclusionThe labour productivity index is the latest in a long line of performance measures promulgated by the Department of Health.As with other summary measures, such as the efficiency index, it is theoretically flawed, wrongly constructed, and suffers from data linmitations.The index could be improved-for example, by: * including omitted activities such as teaching, research, and diagnostic services * weighting or standardising for case mix * using more refined cost weights * including contracted out staff.
Abstract 3498: Synergistic cytotoxicity of everolimus in combination with crizotinib in ALK-positive anaplastic large cell lymphoma cells
Authors: Ji-Won Kim, Wendan Xu, Sung-Soo Yoon
Journal: Cancer Research (2015)

Abstract Everolimus, an mTOR inhibitor, has shown promising anti-tumor activity in a variety of lymphomas, although its clinical efficacy was not satisfactory, due possibly to activation of several pro-surviving signaling pathways. The combined effect of everolimus and crizotinib, an ALK inhibitor, has not yet been investigated in ALK-positive anaplastic large cell lymphoma (ALCL). We treated ALK-positive ALCL cell lines, K-299 and SU-DHL-1, with various concentrations of everolimus and crizotinib at a fixed ratio of 1:40 (0.5 nM, 1.0 nM, and 2.0 nM for everolimus, and 20 nM, 40 nM, and 80 nM for crizotinib, respectively). After 72 hours, the combination index (CI) values were less than 1 (0.596, 0.583, and 0.763 in K-299 cells, and 0.326, 0.616, and 0.271 in SU-DHL-1 cells, respectively) in all tested combinations, suggesting synergistic cytotoxicity of everolimus and crizotinib. Western blot analysis demonstrated that everolimus up-regulated phosphorylation of ERK Thr202/Tyr204 and AKT Thr308 and Ser473. However, this aberrant activation of ERK and AKT was attenuated by the addition of crizotinib. In addition, while everolimus selectively inhibited mTOR Ser2448 phosphorylation, a marker for mTORC1 activity, the combination treatment more potently inhibited mTOR Ser2448 phosphorylation and decreased mTOR Ser2481 phosphorylation, a marker for mTORC2, as well. Cell-cycle analysis showed that the combination treatment induced G1 arrest. PARP cleavage was also increased after the combination treatment. To test the hypothesis that our findings could be applyed to other ALK-positive malignancies, we treated NCI-H2228, a lung adenocarcinoma cell line that harbors an EML4-ALK fusion gene, with everolimus and crizotinib for 72 hours. The CI values were less than 1 in all tested combinations: 0.228 in 1 nM everolimus plus 80 nM crizotinib, 0.216 in 2 nM everolimus plus 160 nM crizotinib, and 0.349 in 4 nM everolimus and 320 nM crizotinib. In summary, everolimus in combination with crizotinib synergistically inhibited the growth of ALK-positive ALCL cells. Crizotinib abrogated aberrant ERK and AKT activation induced by everolimus and more potently inhibited both mTORC1 and mTORC2 activity when combined with everolimus, resulting in increased G1 cell-cycle arrest and apoptosis. Our findings may provide an evidence for future research using everolimus and crizotinib combination in ALK-positive ALCL and could be used to improve the therapeutic outcome in patients with ALK-positive ALCL. Citation Format: Ji-Won Kim, Wendan Xu, Sung-Soo Yoon. Synergistic cytotoxicity of everolimus in combination with crizotinib in ALK-positive anaplastic large cell lymphoma cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3498. doi:10.1158/1538-7445.AM2015-3498
Abstract 19029: The Sirt1 Activator, SRT1720, Attenuates Cardiac Hypertrophy and Fibrosis in a Rodent Pressure Overload Model
Authors: Christopher M Ford, Robert A Civitarese, Antoinette Bugyei-Twum, Melissa Mitchell, Jean-Francois Desjardins, Kerri Thai, Armin Abadeh, Yanling Zhang, Jennifer Switzer, Andrew Advani, Richard E Gilbert, Kim A Connelly
Journal: Circulation (2014)

Background:  Transforming growth factor β1  ( TGFβ1) is a prosclerotic cytokine involved in cardiac remodeling leading to heart failure (CHF). In order to precisely regulate TGFβ1 signaling, acetylation/de-acetylation of lysine 19  within the MH1 domain of Smad2 has been shown to alter DNA binding and transcriptional activity. Recently the lysine de-acetylase Sirt1 has been shown to have a cardioprotective effect, however both Sirt1 expression and activity are reduced in CHF. We hypothesized that pharmacological activation of Sirt1 using SRT1720 would induce cardioprotection in a transverse aortic constriction (TAC) model through modulation of TGF-s/Smad signaling.   Methods:  Wildtype C57BL/6 mice were randomized to receive TAC or sham surgery at 8 weeks of age; each group was subsequently randomized to receive SRT1720 (100mg/kg/day) or placebo, administered once daily via oral gavage. Six weeks following TAC, cardiac function was assessed followed by left ventricular (LV) tissue collection for analysis.   Results:  Animals randomized to TAC demonstrated reduced systolic function, LV hypertrophy and increased fibrosis (all p   Conclusion:  Treatment of mice with SRT1720 improves cardiac function and reduces cardiac fibrosis and hypertrophy following TAC. Given that Sirt1 expression and activity are reduced in CHF, enhancing Sirt1 activity may represent a novel intervention to reduce TGF-s mediated fibrosis.
Abstract 3753: Copper-chelator exerts synergistic interaction with platinum drugs through modulating copper transporters in oxaliplatin-resistant human gastric cancer cell
Authors: Szu-Jung Chen, Jang-Yang Chang, Ching-Chuan Kuo, Hsin-Yi Pan
Journal: Cancer Research (2014)

Abstract Although platinum-based chemotherapy drugs including cisplatin, carboplatin, and oxaliplatin are commonly used in the treatment of human solid tumor, patients ultimately develop drug-resistance and result in treatment failure. Combination copper-chelator with platinum drugs has been reported to successfully treat a subset of cisplatin- resistant ovarian cancer patients. However, the underlying mechanisms of action remain unknown. We have previously established an oxaliplatin-resistant subclone from human gastric adenocarcinoma TSGH cells, S3. The mechanisms responsible for oxaliplatin resistance of S3 cells included down-regulation of hCtr1 and over-expression of ATP7A. In contrast to displaying additive to antagonistic interaction with platinum drugs in parental, TSGH cells, our studies showed that copper-chelator, D-penicillamine, exerts synergistic interaction with platinum drugs through increasing platinum- DNA adduct formations in S3 cells. D-penicillamine promotes copper uptake transporter hCtr1 expression via activation of transcription factor Sp1. In addition, Sp1 overexpression promotes p53 translocation from nucleus to cytosol and binds to ubiquitin, and finally causes p53 degradation, which further suppressed the expression of copper efflux transporter, ATP7A. Combination of D-penicillamine and oxaliplatin significantly inhibited S3 cell growth in animal model. Immunohistochemical analysis showed that up-regulation of hCtr1 and down-regulation of ATP7A were found in both D-penicillamine- and D-penicillamine/ Oxalipatin- treated S3 tumors, which were consistence to in vitro results. In conclusion, our results showed that D-penicillamine increases hCtr1 expression through regulating Sp1 level. Notably, D-penicillamine could down-regulate ATP7A expression through regulation of p53. Our finding demonstrated a new treatment strategy for cancer patient resistant to oxaliplatin treatment with low expression of hCtr1 and overexpression of ATP7A in tumor tissues. (This work was partially supported by the following grants: Department of Health, Taiwan DOH99-TD-C-111-004, National Health Research Institutes CA-101-PP-22, National Research Program for Biopharmaceuticals 100CAP015-5 and National Science Council 102-2325-B-400 -007) Citation Format: Szu-Jung Chen, Jang-Yang Chang, Ching-Chuan Kuo, Hsin-Yi Pan. Copper-chelator exerts synergistic interaction with platinum drugs through modulating copper transporters in oxaliplatin-resistant human gastric cancer cell. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3753. doi:10.1158/1538-7445.AM2014-3753
Abstract 4750: Transcriptome sequencing of the Reed-Sternberg cells of classical Hodgkin lymphoma
Authors: Jonathan Reichel, Joshua Brody, Olivier Elemento, Raul Rabadan, Ethel Cesarman
Journal: Cancer Research (2015)

Abstract Introduction: Most genomic studies of classical Hodgkin lymphoma (cHL) have been confined to cell lines due to the difficulty of isolating sparsely distributed Hodgkin and Reed-Sternberg (HRS) cells from reactive background tissue. One approach to evaluate primary cases has been to microdissect HRS cells from fresh-frozen tissue biopsies, which has been used for gene expression profiling and array comparative genomic hybridization to assess copy number alterations. However, laser capture microdissection is technically challenging, does not provide a pure tumor cell population, and yields very small amounts of degraded nucleic acids that may not be adequate for whole-transcriptome level RNA sequencing. Methods: We used a flow cytometric cell isolation method, which has enabled rapid isolation of thousands of viable HRS cells from primary cHL tumors (Fromm, et al., Am J Clin Pathol 126, 2006). Here we combined flow cytometry using CD64, CD95, CD30, CD5, CD20, CD15, CD40, and CD45, with the Arcturus PicoPure RNA Isolation kit to isolate high quality RNA from viable HRS cells and intratumor B cells from nine primary cases of CHL respectively. We applied the Clontech SMARTer Ultra Low Input RNA Kit followed by Kapa Library Preparation kit to generate what is to our knowledge the first full transcriptome RNA sequence data from primary cases of cHL. Four cell lines were sequenced using the same methodology. We performed differential expression and gene fusion analyses, and conducted a search for activated pathways. Results: We report the expression signature of purified primary HRS cells. PCA analysis showed that these segregate from HRS cell lines and primary B cells. We confirmed at the RNA level overexpression of relevant amplified genes for which inhibitors are available (AURKA and EZH2), and underexpression of transcripts encoded by genes previously found to be deleted (for example ATM). Pathway analysis revealed extensive downregulation of antigen presentation, consistent with our previous exome sequence analysis showing mutations in beta-2 microglobulin as the most common genetic alteration. Results of the mutational and transcriptional landscape of the HRS cells will be presented. Conclusions: Transcriptome-level analysis of flow-sorted HRS cells allows for expanded study of CHL pathogenesis, new target identification based on altered signaling pathways and potentially individualized approaches to CHL therapy. Citation Format: Jonathan Reichel, Joshua Brody, Olivier Elemento, Raul Rabadan, Ethel Cesarman. Transcriptome sequencing of the Reed-Sternberg cells of classical Hodgkin lymphoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4750. doi:10.1158/1538-7445.AM2015-4750
Results of Surgical Treatment of Aortic Stenosis
Authors: C. Baker, J. Somerville
Journal: BMJ (1964)

treatment.We have not included treated by insertion of a homograft at the end of this period.patients who have been aortic valve (Ross, 1962) Method of PresentationThe composition of the series of 200 patients is shown in Table I.They have been primarily divided, according to the anatomy, into 179 patients with valvar stenosis, 20 patients with subvalvar stenosis, and one patient with supravalvar stenosis.The patients with subvalvar and supravalvar aortic stenosis are discussed separately as they present a differen TABLE I.-Analysis of 200 Patients to Show Type of Obstruction Present and Type of Operation Performned Type of Obstruction Valvar Subvalvar . .Supravalvar . .179 20 Type of Operation For valvar stenosis Closed transventricular valvotomy (90) Baker and Campbell (1956) (not discussed) Uncalcifled valvar stenosis (not discussed) Calcified valvar stenosis Open aortic valvotomy (89) Hypothermia (not discussed).By-pass; uncalcified valvar stenosis calcified valvar stenosis For subvalvar stenosis Closed operation Open operation For supravalvar stenosis: open operation .
Health Effects of Video Display Terminals
Authors: T. Bergman
Journal: JAMA (1987)

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