tbuckley/cabot-search huggingface dataset:
Targetable T-type Calcium Channels Drive Glioblastoma
Authors: Ying Zhang, Nichola Cruickshanks, Fang Yuan, Baomin Wang, Mary Pahuski, Julia Wulfkuhle, Isela Gallagher, Alexander F. Koeppel, Sarah Hatef, Christopher Papanicolas, Jeongwu Lee, Eli E. Bar, David Schiff, Stephen D. Turner, Emanuel F. Petricoin, Lloyd S. Gray, Roger Abounader
Journal: Cancer Research (2017)

Abstract Glioblastoma (GBM) stem-like cells (GSC) promote tumor initiation, progression, and therapeutic resistance. Here, we show how GSCs can be targeted by the FDA-approved drug mibefradil, which inhibits the T-type calcium channel Cav3.2. This calcium channel was highly expressed in human GBM specimens and enriched in GSCs. Analyses of the The Cancer Genome Atlas and REMBRANDT databases confirmed upregulation of Cav3.2 in a subset of tumors and showed that overexpression associated with worse prognosis. Mibefradil treatment or RNAi-mediated attenuation of Cav3.2 was sufficient to inhibit the growth, survival, and stemness of GSCs and also sensitized them to temozolomide chemotherapy. Proteomic and transcriptomic analyses revealed that Cav3.2 inhibition altered cancer signaling pathways and gene transcription. Cav3.2 inhibition suppressed GSC growth in part by inhibiting prosurvival AKT/mTOR pathways and stimulating proapoptotic survivin and BAX pathways. Furthermore, Cav3.2 inhibition decreased expression of oncogenes (PDGFA, PDGFB, and TGFB1) and increased expression of tumor suppressor genes (TNFRSF14 and HSD17B14). Oral administration of mibefradil inhibited growth of GSC-derived GBM murine xenografts, prolonged host survival, and sensitized tumors to temozolomide treatment. Our results offer a comprehensive characterization of Cav3.2 in GBM tumors and GSCs and provide a preclinical proof of concept for repurposing mibefradil as a mechanism-based treatment strategy for GBM. Cancer Res; 77(13); 3479–90. ©2017 AACR.
Unmanipulated Haploidentical Bone Marrow Transplantation and Post-Transplant Cyclophosphamide for Hematologic Malignanices Following A Myeloablative Conditioning.
Authors: Andrea P Bacigalupo, Anna Maria Raiola, Alida Dominietto, Maria Teresa Van Lint, Francesca Gualandi, Teresa Lamparelli, Stefania Bregante, Anna Ghiso, Carmen Di Grazia, Riccardo Varaldo
Journal: Blood (2012)
Simon Stevens uses art to sidestep purdah
Authors: Tom Moberly
Journal: BMJ (2017)

At the King’s Fund’s annual conference on leadership and management last week, NHS England’s chief executive, Simon Stevens, found an innovative way to deal with the challenge of discussing the next steps for the health service within the restrictions of pre-election purdah.

Stevens began by saying sorry. “I apologise that your conference has fallen during one of our annual major political events in this country, with general elections, …
A comparative analysis of locoregional therapy (hyperthermic intraperitoneal chemotherapy [HIPEC]) and systemic chemotherapy (CT) following cytoreductive surgery in patients (pts) with disseminated mucinous appendiceal cancers (MACA).
Authors: Tanios S. Bekaii-Saab, Ludmila Katherine Martin, Geetha D. Vallabhaneni, Wungki Park, Charles A. Staley, Shishir Kumar Maithel, Zhibo Wang, Zhengjia Chen, Bassel F. El-Rayes
Journal: Journal of Clinical Oncology (2012)

e14169 Background: MACA are rare neoplasms with variable prognosis depending on tumor histology. Peritoneal dissemination is frequent and cytoreductive surgery is the mainstay of treatment (tx). HIPEC and CT may provide additional benefit, but their role is not well understood. We evaluated the role of HIPEC and CT in pts with MACA following cytoreduction. Methods: Pertinent data including demographics, tx and clinical outcome were retrospectively obtained from pts treated at The Ohio State University and Emory University. Tumors were histologically classified as disseminated peritoneal adenomucinosis (DPAM) or peritoneal mucinous carcinomatosis (PMCA) and by TNM stage. Clinical outcome was evaluated according to tx, stage, and histology. Results: 124 pts (41M, 83F) with a median age of 58 years (range 21-82) were included. All pts had stage IV disease, 43 had DPAM and 71 had PMCA (10 unavailable). Following debulking surgery, 27% of pts had HIPEC, 21% had CT, 30% had both and 22% had no additional therapy. For stage IV pts, there was a significant benefit for additional tx after surgery (Table). Pts with DPAM had significantly improved mOS versus PMCA. For pts with PMCA but not DPAM a significant survival advantage was seen for any tx (CT, HIPEC, or both) versus no therapy following surgery. Conclusions: For pts with MACA, additional tx may improve survival following cytoreductive surgery. HIPEC appears to improve outcomes, while systemic CT may not provide added benefit. Prognosis for DPAM histology appears to be superior to PMCA. Pts with PMCA may benefit most from additional tx following cytoreduction. These interesting findings are limited by their retrospective nature and prospective validation is needed. [Table: see text]
Therapeutic Drug Monitoring of Posaconazole in Adult Acute Myeloid Leukemia (Aml) Patients Receiving Posaconazole Prophylaxis during Induction: Experience from a Center with High Invasive Fungal Infection (IFI)Burden
Authors: Manju Sengar, Sanyo Dsouza, Raviraj Deshpande, Hasmukh Jain, Murari Gurjar, Sadhana Kannan, Nayana Morajkar, Vikram Gota
Journal: Blood (2016)
NF-κB p50 (nfkb1) contributes to pathogenesis in the Eμ-TCL1 mouse model of chronic lymphocytic leukemia
Authors: Timothy L. Chen, Minh Tran, Aparna Lakshmanan, Bonnie K. Harrington, Nikhil Gupta, Virginia M. Goettl, Amy M. Lehman, Stephen Trudeau, David M. Lucas, Amy J. Johnson, John C. Byrd, Erin Hertlein
Journal: Blood (2017)
Abstract 19716: Zebrafish Larvae as a Model System For High-throughput Screens of Early-stage Atherosclerosis
Authors: Manoj K Bandaru, Petter Ranefall, Anastasia Emmanouilidou, Lingjie Tao, Anders Larsson, Johan Ledin, Carolina Wählby, Erik Ingelsson, Marcel den Hoed
Journal: Circulation (2015)

Introduction: A high-cholesterol diet has been reported to induce vascular deposition of lipids and oxidized LDL cholesterol in macrophages and other cell types in 15 day-old zebrafish larvae. However, results were based on small samples, and little is known about the heterogeneity of effect within and between conditions, the image quantification procedure used, and the influence of dietary energy. We intend to perform large-scale genetic and compound screens for coronary heart disease, and aimed to confirm or refute if zebrafish larvae are a suitable model system. Methods: In total, 940 transgenic zebrafish larvae were fed on one of six diets between 5 and 10 days post-fertilization (dpf), to examine main effects of, and interactions between dietary energy and cholesterol. At 10 dpf, we assessed body length and acquired optical sections of the dorsal aorta and caudal vein using an automated positioning system, fluorescence microscope and CCD camera. Atherogenic traits were quantified using a custom-written image analysis pipeline in Ilastik, CellProfiler and ImageJ, and larvae were used to assess whole body levels of total cholesterol, triglycerides and glucose using enzymatic assays. Associations were adjusted for body length, ether - used to prepare the high-cholesterol diet - and batch. Results: A high-energy diet resulted in elevated triglyceride levels (p=7.8E-3) - especially in the presence of high dietary cholesterol (p-interaction=0.01) - and in more vascular infiltration by lipids (p=1.0E-12), and co-localising lipids and macrophages (p=0.04), independently of dietary cholesterol. A high-cholesterol diet resulted in higher glucose levels (p=2.1E-3), and in more vascular infiltration by lipids (p=0.01), and co-localising lipids and neutrophils (p=0.04), and lipids, neutrophils and macrophages (p=0.01), independently of dietary energy. Qualitative analyses showed that vascular lipid deposits typically contain oxidised LDL cholesterol, and are located at bifurcation sites of the endothelium. Conclusions: Zebrafish larvae represent a promising model system for high-throughput, image-based screens of early-stage atherosclerosis, and dietary energy and cholesterol induce distinct atherogenic traits as early as 10 dpf.
Mast Cells and KIT as Potential Therapeutic Targets in Severe Asthma
Authors: Stephen J. Galli
Journal: New England Journal of Medicine (2017)

Mast cells and many of their secreted products have long been thought to contribute to the pathologic processes underlying asthma,1,2 but no clinical studies have assessed whether specifically targeting mast-cell survival or development would have therapeutic benefit in the treatment of this disorder. In this issue of the Journal, Cahill and colleagues3 report the results of a randomized, double-blind, placebo-controlled, phase 2, 24-week, proof-of-principle trial in which patients with severe, poorly controlled asthma were treated with the tyrosine kinase inhibitor imatinib, which can inhibit KIT,4 the major survival and growth factor for mast cells.2 The total number of patients . . .
Abstract 342: Increased Myocardial Ischemic/Reperfusion Injury in Renal Failure Involves Cardiac Adiponectin Signal Deficiency
Authors: Ling Tao, Yanbin Song, Junyi Zhang, Weidong Huang, Yi Liu, Lu Sun, Haifeng Zhang, Haichang Wang, Yan Qu
Journal: Circulation Research (2013)

Chronic kidney disease (CKD) is associated with increased incidence as well as adverse outcomes of acute myocardial infarction. Adiponectin (APN), known as a cardioprotective factor, has been observed decreased in cardiovascular disorders including myocardial infarction. However, plasma APN levels are significantly increased and are inversely related to the risk of cardiovascular morbidity and mortality in patients with CKD. The mechanism underlying the paradoxical relationship between high APN and poor cardiac outcome remains unclear. In the present study, subtotal nephrectomized (SN) and sham-operated mice were randomly subjected to a 30 min myocardial ischemia followed by 24 hrs reperfusion with or without human recombinant gAd treatment (2μg/g/d, 7days). Compared with sham WT mice, SN mice displayed significantly depressed cardiac function and enlarged infarct size following MI/R. TUNEL staining and caspase-3 activity assay demonstrated markedly increased cardiomyocyte apoptosis in SN mice following MI/R. What’s more, increased plasma total APN levels was observed in SN mice 4 weeks after MI/R. Importantly, SN caused further decreased cardiac function and larger infarct size in APN knockout (KO) mice compared with those in SN WT mice subjected to MI/R. However, gAd treatment significantly enhanced cardiac function and reduced infarct size and apoptosis in both WT and KO mice. Further, we found that SN KO mice showed more reduced eNOS phosphorylation, upregulated iNOS expression and ·O 2 - production and consequently increased peroxynitrite production in cardiac tissue than SN WT animals, which can be partly reversed by administration of gAd. AdipoR1 expression was reduced 4-wk after SN whereas AdipoR2 showed no significant change. More importantly, AMPK activation was also inhibited after SN and exogenous gAd supplementation reversed this change. In conclusion, the present study demonstrates that renal dysfunction increases cardiac susceptibility to ischemic/reperfusion injury, which is associated with downregulated APN/AdipoR1/AMPK signaling and increased oxidative/nitrative stress in local myocardium, and provides the first evidence for the benefits of exogenous supplement of APN on cardiac outcomes in renal failure.
No evidence for induction of autoantibodies or autoimmunity during treatment of psoriasis with ustekinumab
Authors: P. Rodríguez‐Jiménez, P. Chicharro, A. Godoy, M. Llamas‐Velasco, M. García, E. Daudén
Journal: British Journal of Dermatology (2017)

Ustekinumab is a human monoclonal antibody directed against the p40 subunit of both interleukin (IL)-12 and IL-231. It has shown to be very effective in the treatment of moderate-to-severe plaque psoriasis and psoriatic arthritis with a good safety profile2,.In the last ten years, the appearance of antinuclear antibodies (ANA) and the induction of autoimmune diseases during treatment with tumour necrosis factor-alpha (TNFα) inhibitors has been described 3-4.

This article is protected by copyright. All rights reserved.
Steroid injections for knee osteoarthritis are not supported by study
Authors: Jacqui Wise
Journal: BMJ (2017)

Corticosteroid injections for knee osteoarthritis produced no benefit in a double blind randomised controlled trial reported in JAMA .1

The two year US study found that, when compared with saline, injections with triamcinolone resulted in significantly greater cartilage volume loss and no significant difference in knee pain.

Osteoarthritis is a leading cause of disability, and no known treatments stop progression of the painful condition.

Researchers from Tufts …
Rook's Textbook of Dermatology, 9th edn. ChristopherGriffiths, JonathanBarker, TanyaBleiker, RobertChalmers, DanielCreamer, eds. Publisher: Wiley-Blackwell, 2016; 4696 pp. ISBN: 978-1118441190. Price £522.50.
Authors: S. Fatah
Journal: British Journal of Dermatology (2017)
Guidelines for cardiopulmonary resuscitation and emergency cardiac care. Emergency Cardiac Care Committee and Subcommittees, American Heart Association. Part II. Adult basic life support
Journal: JAMA (1992)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
In <i>C difficile</i> infection, adding IV bezlotoxumab to standard antibiotics reduced recurrence at 12 weeks
Authors: Fred Arthur Zar
Journal: Annals of Internal Medicine (2017)

Source Citation Wilcox MH, Gerding DN, Poxton IR, et al; MODIFY 1 and MODIFY II Investigators. Bezlotoxumab for prevention of recurrent Clostridium difficile infection. N Engl J Med. 2017;376:305-17. 28121498
Adverse Events in Colorectal Surgical Patients Remaining in Hospital whilst Awaiting Medical Review, Rehabilitation or Long-Term Placement
Authors: T Kallachil, K Sevar, C Benzoni, T Daniel
Journal: Endoscopy (2006)

Aims: To evaluate the adverse events occurring in patients that are surgically fit for discharge but remain in an acute surgical unit whilst awaiting specialist medical review, rehabilitation or long-term placement.
Innovative delivery method using a detachable device to deliver a large polyglycolic acid sheet to a gastric ulcer perforation
Authors: Hirohito Mori, Hideki Kobara, Asadur Rahman, Noriko Nishiyama, Akira Nishiyama, Yasuyuki Suzuki, Tsutomu Masaki
Journal: Endoscopy (2017)

Many reports have indicated the efficacy of polyglycolic acid (PGA) sheets with fibrin glue for the treatment of perforations or preventing stricture following endoscopic submucosal dissection (ESD) [1] [2]. However, the delivery method of such a thin membrane such as the PGA sheet (especially large sheets) into the stomach without getting wet has not been reported.
Association of paclitaxel-induced sensory peripheral neuropathy with the <i>ABCB1</i> genetic variant and age.
Authors: Chikako Shimizu, Yuko Tanabe, Akinobu Hamada, Mayu Yunokawa, Toshimi Takano, Shigehiro Koganemaru, Ozaki Yukinori, Nobuko Tamura, Yasuhiro Fujiwara, Kenji Tamura
Journal: Journal of Clinical Oncology (2015)

11100 Background: The development of paclitaxel-induced peripheral neuropathy (PIPN) is influenced by the age and genetic composition of patients. Paclitaxel is known to act as a substrate in SLCO1B3-mediated influx, ABCB1-mediated efflux from cancer cells, and CYP2C8-mediated metabolism. We conducted a prospective study to investigate whether age and these single nucleotide polymorphisms (SNPs) are correlated with PIPN. Methods: Breast cancer patients who received adjuvant weekly paclitaxel were genotyped for five SNPs in three genes, including rs4149117 in SLCO1B3; rs2032582, rs1045642, and rs1128503 in ABCB1; and rs10509681 in CYP2C8, using PCR quenching probe method. Clinical data, including the paclitaxel dose and onset and severity of neuropathy, were correlated with the genetic data. Results: We enrolled 127 Japanese patients with a median age of 50 years (range, 25–75 years). The mean total paclitaxel dose administered was 933 mg/m2 (range, 560–960 mg/m2), and 85% received the full dose intensity treatment (960 mg/m2 over 12 weeks). The majority of patients (98.4%) developed all grade neuropathy, and 51.9% of patients exhibited grade 2 or higher severity. Severe neuropathy, defined as those requiring a dose delay, dose reduction, or early termination of chemotherapy, occurred in 15.0% of patients. Of the five SNPs evaluated, the ABCB1 (rs1128503) TT genotype was associated with a grade 2 or higher neuropathy compared with the CC/CT genotype (p = 0.05). Of note, patients with the TT genotype aged > 60 years had a higher incidence of grade 2 or higher severity (p = 0.008) than those with the CC/CT genotype. Patients without PIPN were all wild type for the five SNPs. Patients aged > 60 years had a higher incidence of grade 2 or higher severity (p = 0.006) than younger patients, regardless of the SNPs. Conclusions: ABCB1 rs1128503 SNP and advanced age are correlated with PIPN. This findings may help clinicians determine which patients should avoid paclitaxel. Clinical trial information: UMIN000005294.
Unusual and memorable
Authors: G. D Wright
Journal: Annals of the Rheumatic Diseases (1998)

might reduce the economic costs to society of back pain, these eVects would be limited if no account is taken of the influence of broader non-work related aspects.Moreover, for the individual, such interventions are unlikely to impact on the overall experience of back pain and consultation behaviour.The authors thank the partners, staV, and patients of Brooklands and Bowland Road General Practices, Manchester, UK, for their support and cooperation, Lesley
Unusual Hematologic Malignancies
Authors: C.S. Chim, C.C.K. Lam, J.M. Nicholls, G.C. Ooi, Y.L. Kwong
Journal: Journal of Clinical Oncology (2002)

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.2002.20.17.3742 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12202676 Unusual Hematologic Malignancies Case 3. CNS Involvement in CD56-Positive Intestinal Gamma/Delta T-Cell Lymphoma C.S. ChimxC.S. ChimSearch for articles by this author , C.C.K. LamxC.C.K. LamSearch for articles by this author , J.M. NichollsxJ.M. NichollsSearch for articles by this author , G.C. OoixG.C. OoiSearch for articles by this author , Y.L. KwongxY.L. KwongSearch for articles by this author Show More Queen Mary Hospital, Hong Kong https://doi.org/10.1200/JCO.2002.20.17.3742 First Page Full Text PDF Figures and Tables © 2002 by American Society of Clinical Oncology
Incidence and characteristics of breast cancer following a diagnosis of ductal carcinoma in situ.
Authors: Xiudong Lei, Shaheenah S. Dawood, Constance T. Albarracin, Rebecca Dent, Sudeep Gupta, Javier Cortes, Elizabeth Ann Mittendorf, Thomas A. Buchholz, Ana M. Gonzalez-Angulo
Journal: Journal of Clinical Oncology (2013)

1131 Background: Recent data indicate that the incidence of DCIS is rising. The purpose of this retrospective population based study was to examine incidence of and factors that contribute to the development of a subsequent breast primary. Methods: Using the SEER registry we identified female pts with a primary DCIS diagnosed between 1990 to 2005. Pts who had an invasive or in situ malignancy diagnosed prior to a diagnosis of DCIS were excluded. Cumulative incidence of a subsequent breast primary (invasive/non invasive) was estimated and compared across groups using the Chi-square test. Multivariable logistic regression models were then fitted to determine factors that could predict for the development of a subsequent breast primary. Results: 96,130 pts were identified of whom 14,573 (15.2%) had subsequent primaries. 9,037 (62%) pts had a subsequent primary in the breast of which 5,915 (65.5%) pts had an invasive breast cancer. Among pts who developed an invasive breast cancer 68% had hormone receptor positive disease, 59% had grade I/II disease and 80% had stage I/II disease. 2 and 5-year cumulative incidence of developing a subsequent breast primary was 3.2% and 5.9% respectively. 2 and 5-year cumulative incidence of developing a subsequent invasive breast primary was 1.6% and 3.4% respectively. 5-year cumulative incidence of developing a subsequent breast primary among pts who were of white, black and other race was 5.8%, 6.8% and 6.1% respectively (P&lt;0.001). In the multivariable logistic model the probability of developing a subsequent breast primary decreased with each increasing year of diagnosis of DCIS (OR 0.91, 95%CI 0.91-0.92, p&lt;0.001). Other factors that predicted for the development of a subsequent breast primary included younger age at diagnosis, non-white race and lack of surgical or radiation therapy for DCIS. Conclusions: Our results indicate that a significant proportion of pts with a diagnosis of DCIS go on to develop invasive breast cancer and may warrant further investigation to determine biological risk factors, appropriate screening procedures and possible interventions to decrease incidence. Target groups that may benefit include pts who are young and of non white race at the time of diagnosis of DCIS.
Alveolar Derecruitment at Decremental Positive End-Expiratory Pressure Levels in Acute Lung Injury
Authors: SALVATORE M. MAGGIORE, BJÖRN JONSON, JEAN-CHRISTOPHE RICHARD, SAMIR JABER, FRANÇOIS LEMAIRE, LAURENT BROCHARD
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

We examined the hypothesis that recording multiple elastic pressure–volume (Pel/V) curves and calculating alveolar derecruitment (VDER) induced by decreasing positive end-expiratory pressure (PEEP) may allow determination of alveolar closing pressures, thus helping to select the optimal PEEP level. VDER measured in 16 patients with acute lung injury (ALI) was compared with the lower inflection point (LIP) and oxygenation changes. A modified automated method was used to record multiple Pel/V curves at low constant flow. PEEP was decreased in 5-cm H2O steps, from 20 or 15 cm H2O to 0 cm H2O (ZEEP). VDER was the volume loss between the curves recorded from PEEP and from ZEEP at the same Pel. Derecruitment occurred at each PEEP decrement, being spread almost uniformly over the 20/15 to 0 cm H2O range. VDER was not correlated with LIP. VDER changes correlated with PaO2 /Fi O2 changes (rho = 0.6, p = 0.02). Linear compliance at ZEEP was correlated to VDER at PEEP 15 cm H2O (rho = 0.9, p = 0.001), suggesting that compliance above LIP may reflect the amount of recruitable lung. Thus, alveolar closure in ALI occurs over a wide range of pressures, and LIP is a poor predictor of alveolar closure.Keywords: PEEP; derecruitment; elastic pressure–volume curves; lower inflection point; acute lung injury