tbuckley/cabot-search huggingface dataset:
Diagnostic histologique des masses pancréatiques par les aiguilles de 25 G avec ou sans fenêtre latérale: un essai multicentrique randomisé
Authors: M. Palazzo
Journal: Endoscopy (2016)

La ponction guidée par échoendoscopie est essentielle dans la prise en charge des tumeurs solides du pancréas. Sa précision diagnostique varie entre 80 et 95 % selon les études. Le choix du type d’aiguille est crucial pour cette technique. Les aiguilles de petit calibre (25 G) sont plus faciles à utiliser, pénètrent mieux la lésion cible et entraînent moins de contamination du prélèvement par du sang. Leur rendement diagnostique est bon en raison d’une qualité cytologique suffisante. Néanmoins, la qualité des prélèvements à visée histologique est faible et inférieure à celle obtenue avec des aiguilles de plus gros diamètre. Récemment, un nouveau type de matériel comportant une fenêtre latérale et permettant d’obtenir une carotte histologique est disponible. Le but de cette étude était d’évaluer la précision diagnostique et la capacité d’obtention de prélèvements à visée histologique des aiguilles 25 G avec fenêtre latérale.
Phase I trial of combination of antitumor immunotherapy targeted against <i>cytomegalovirus</i> (CMV) plus regulatory T-cell inhibition in patients with newly-diagnosed glioblastoma multiforme (GBM).
Authors: Gordana Vlahovic, Gerald E. Archer, Elizabeth Reap, Annick Desjardins, Katherine B. Peters, Dina Randazzo, Patrick Healy, James Emmett Herndon, Allan H. Friedman, Henry S. Friedman, Darell D. Bigner, John H. Sampson
Journal: Journal of Clinical Oncology (2016)

e13518 Background: The inherent biologic specificity of immunotherapy offers the prospect of targeting neoplastic cells more precisely. Dendritic cells (DCs) are endowed with an extraordinary ability to activate CD4+ and CD8+ T-cells, and DCs loaded with antigens derived from tumor cells (CMV pp65-LAMP mRNA) have the potential to induce potent antitumor immunity. Furthermore, regulatory T-cells (TRegs ) which induce a state of reversible immunosuppression in mg can be functionally inactivated with anti-CD25 antibody (Ab), while dramatically enhancing vaccine-induced immune responses. Previously a group of 7 pts received DC CMV vaccine with one dose of anti-CD25 Ab (daclizumab). A median overall survival (OS) of 30.3 months (95% CI: 11.8%, 60.8%) was seen without adverse events associated with the vaccine or anti-CD25 Ab therapy. Methods: Eligible were gross totally resected pts with newly diagnosed GBM. Patients underwent leukapheresis followed by standard of care radiation/temozolomide (XRT/TMZ) therapy. After completion of XRT/TMZ, up to 12 cycles of TMZ was administered. On Day 21 of the 1st cycle of post-XRT TMZ Vaccine # 1 was administered. Vaccines #2-3 were given biweekly following vaccine #1. Anti-CD25 Ab (basiliximab) was given twice, one week before vaccines 1 and 2. In this dose escalation study two dose levels were examined: 20 or 40 mg. An additional vaccine was given with each cycle of TMZ to a total of 8. Multiple time-point immune-monitoring by kinetics of number of TRegs and pp65 specific T cells by INFγ ELISPOT was performed for each pt. Results: None of the 28 patients who received any protocol treatment experienced a DLT. One patient experienced an SAE: grade 2 fever and grade 3 confusion. To date, only 2 patients have expired. Among patients who received at least 3 vaccinations, median follow-up is 5.6 months (95% CI: 3.6, 9.9). Median PFS is 7.7 months (95% CI: 3.4, 13.8). Preliminary evaluation of 6 patients' blood provided no evidence of a difference between dose groups in CD4% or Treg% post-basiliximab treatment. Conclusions: Phase I study is closed for accrual; 20 mg of basiliximab is used in Phase II trial. Clinical trial information: NCT00626483.
Abstract 10041: Increased Triglyceride Levels are Associated With Endothelial Dysfunction: FMD-Japan Registry
Authors: Masato Kajikawa, Yukihito Higashi, Tatsuya Maruhashi, Yumiko Iwamoto, Akimichi Iwamoto, Nozomu Oda, Shinji Kishimoto, Takayuki Hidaka, Kensuke Noma, Hirofumi Tomiyama, Bonpei Takase, Akira Yamashina, Yasuki Kihara
Journal: Circulation (2015)

Objective: In contrast to low-density lipoprotein cholesterol, and high density lipoprotein cholesterol, which are well-established independent risk factors for cardiovascular disease, the importance of triglycerides remains controversial. In this study, we evaluated the associations between triglycerides and endothelial function in the general population. Methods and Results: We enrolled 4,908 subjects (3842 men and 1066 women; mean age, 48±12 years) who were enrolled in FMD-Japan registry. And, we investigated cross-sectional associations between triglycerides and endothelial function by measurement of flow-mediated vasodilation (FMD). The triglycerides levels were negatively associated with FMD (r=-0.10, P&lt;0.001). Subjects were divided into six groups on the basis of the triglycerides level. FMD was significantly decreased with an increase in the triglycerides level (≤63 mg/dL, 7.0±3.5%; 64 to 83 mg/dL, 6.3±3.5%; 84 to 105 mg/dL, 6.0±3.1%; 106 to 131 mg/dL, 5.8±3.2%; 132 to 179 mg/dL, 5.7±3.1%; ≥180 mg/dL, 5.5±3.0%; P for trend&lt;0.001). After adjustment for age, sex, cardiovascular risk factors including high density lipoprotein cholesterol, high triglycerides level groups independently remained associated with low quartile of FMD using the triglycerides ≤63 mg/dL group as the reference (Table). Conclusions: These findings supported an independent association between triglycerides and cardiovascular disease.
Aldehyde dehydrogenases inhibition eradicates leukemia stem cells while sparing normal progenitors
Authors: G Venton, M Pérez-Alea, C Baier, G Fournet, G Quash, Y Labiad, G Martin, F Sanderson, P Poullin, P Suchon, L Farnault, C Nguyen, C Brunet, I Ceylan, R T Costello
Journal: Blood Cancer Journal (2016)

The vast majority of patients with acute myeloid leukemia (AML) achieve complete remission (CR) after standard induction chemotherapy. However, the majority subsequently relapse and die of the disease. A leukemia stem cell (LSC) paradigm has been invoked to explain this failure of CR to reliably translate into cure. Indeed, LSCs are highly enriched in CD34+CD38- leukemic cells that exhibit positive aldehyde dehydrogenase activity (ALDH+) on flow cytometry, these LSCs are resistant to currently existing treatments in AML such as cytarabine and anthracycline that, at the cost of great toxicity on normal cells, are highly active against the leukemic bulk, but spare the LSCs responsible for relapse. To try to combat the LSC population selectively, a well-characterized ALDH inhibitor by the trivial name of dimethyl ampal thiolester (DIMATE) was assessed on sorted CD34+CD38- subpopulations from AML patients and healthy patients. ALDH activity and cell viability were monitored by flow cytometry. From enzyme kinetic studies DIMATE is an active enzyme-dependent, competitive, irreversible inhibitor of ALDH1. On cells in culture, DIMATE is a powerful inhibitor of ALDHs 1 and 3, has a major cytotoxic activity on human AML cell lines. Moreover, DIMATE is highly active against leukemic populations enriched in LSCs, but, unlike conventional chemotherapy, DIMATE is not toxic for healthy hematopoietic stem cells which retained, after treatment, their self-renewing and multi-lineage differentiation capacity in immunodeficient mice, xenografted with human leukemic cells. DIMATE eradicates specifically human AML cells and spares healthy mouse hematologic cells.
Abstract 4802: Transcriptional landscape of lung squamous cell carcinoma in Northeast Asian patients
Authors: Arang Rhie, Hyesun Cho, Min Hwan Son, Seong-Keun Yoo, Jong-Yeon Shin, Jeong-Sun Seo
Journal: Cancer Research (2015)

Abstract Lung Squamous Cell Carcinoma (LSCC), the second most prevalent type of lung cancer, is known to have different genetic and epigenetic characteristics from lung adenocarcinoma. Molecular pathogenesis remains to be elucidated to identify therapeutic targets, especially for patients with no driver mutations identified in previous studies. In this study, we obtained RNAs from fresh tissue of 101 patients of LSCC, and its paired normal site. RNA-seq was performed with paired-end sequencing of HiSeq2000. The average throughput uniquely mapped to the human genome reference was 10Gbp per sample. Differentially expressed genes showed higher expression in HOX families, FOXL2, SOX2, FGFR3, JAK3, and ALK. In contrast, WIF1, RSPO2, ROS1, TAL1, PRDM16 was down regulated in tumor cells. To subgroup patients with their driver mutation, somatic mutation have been detected with comparison to normal paired samples, filtering with MAF&amp;lt;0.01 of Northeast Asian Population, 1KG, and ExAC 65000 exomes. The average number of nonsynonymous somatic mutation was 49.63 per sample. Sixty-seven patients had somatic mutation in TP53, CDKN2A, NFE2L2, and PIK3CA. This was relatively small compared to patients from TCGA, mainly consisting of Western population. After excluding 4 patients identified to be close to normal cells by PCA analysis of expression pattern, and 2 other patients suspected to be false classified from adenocarcinoma presenting mutation in EGFR (L858R) and KRAS (G12D), 28 patients remained to be elucidated. No EGFR, ALK, RET, FGFR3, TACC fusion have been found, suggesting novel isoform of transcripts or other mechanisms driving carcinogenesis. Citation Format: Arang Rhie, Hyesun Cho, Min Hwan Son, Seong-Keun Yoo, Jong-Yeon Shin, Jeong-Sun Seo. Transcriptional landscape of lung squamous cell carcinoma in Northeast Asian patients. [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 4802. doi:10.1158/1538-7445.AM2015-4802
Access to Health Care and Preventable Hospitalizations-Reply
Authors: Barbara Starfield
Journal: JAMA (1995)

In Reply.  —Dr Baker's admonitions about the importance of disease prevalence and severity are well taken, but since the poor have greater disease prevalence and severity, their compromised access is all the more striking. Dr Frey's comments echo my observation that compromised access to services for the socially disadvantaged is nothing new. As for Dr Jameson's comments about the importance of personal health behaviors, the data show clearly that health systems with greater access to care and higher use of primary care resources than in the United States have better health levels 1 despite their greater prevalence of adverse behaviors such as smoking and drinking. 2 His suggestion that access to care has reached the point of diminishing returns may be true for specialty care; it is almost certainly not true for primary care.
Fap2 Mediates Fusobacterium nucleatum Colorectal Adenocarcinoma Enrichment by Binding to Tumor-Expressed Gal-GalNAc
Authors: Jawad Abed, Johanna E.M. Emgård, Gideon Zamir, Mouhammad Faroja, Gideon Almogy, Amalie Grenov, Asaf Sol, Ronit Naor, Eli Pikarsky, Karine A. Atlan, Anna Mellul, Stella Chaushu, Abigail L. Manson, Ashlee M. Earl, Nora Ou, Caitlin A. Brennan, Wendy S. Garrett, Gilad Bachrach
Journal: Cell Host & Microbe (2016)
Inhibition of apolipoprotein B synthesis stimulates endoplasmic reticulum autophagy that prevents steatosis
Authors: Donna M. Conlon, Tiffany Thomas, Tatyana Fedotova, Antonio Hernandez-Ono, Gilbert Di Paolo, Robin B. Chan, Kelly Ruggles, Sarah Gibeley, Jing Liu, Henry N. Ginsberg
Journal: Journal of Clinical Investigation (2016)

Inhibition of VLDL secretion reduces plasma levels of atherogenic apolipoprotein B (apoB) lipoproteins but can also cause hepatic steatosis. Approaches targeting apoB synthesis, which lies upstream of VLDL secretion, have potential to effectively reduce dyslipidemia but can also lead to hepatic accumulation of unsecreted triglycerides (TG). Here, we found that treating mice with apoB antisense oligonucleotides (ASOs) for 6 weeks decreased VLDL secretion and plasma cholesterol without causing steatosis. The absence of steatosis was linked to an increase in ER stress in the first 3 weeks of ASO treatment, followed by development of ER autophagy at the end of 6 weeks of treatment. The latter resulted in increased fatty acid (FA) oxidation that was inhibited by both chloroquine and 3-methyl adenine, consistent with trafficking of ER TG through the autophagic pathway before oxidation. These findings support the concept that inhibition of apoB synthesis traps lipids that have been transferred to the ER by microsomal TG transfer protein (MTP), inducing ER stress. ER stress then triggers ER autophagy and subsequent lysosomal lipolysis of TG, followed by mitochondrial oxidation of released FA, leading to prevention of steatosis. The identification of this pathway indicates that inhibition of VLDL secretion remains a viable target for therapies aiming to reduce circulating levels of atherogenic apoB lipoproteins.
Switching CAR T cells on and off: a novel modular platform for retargeting of T cells to AML blasts
Authors: M Cartellieri, A Feldmann, S Koristka, C Arndt, S Loff, A Ehninger, M von Bonin, E P Bejestani, G Ehninger, M P Bachmann
Journal: Blood Cancer Journal (2016)

Abstract The adoptive transfer of CD19-specific chimeric antigen receptor engineered T cells (CAR T cells) resulted in encouraging clinical trials in indolent B-cell malignancies. However, they also show the limitations of this fascinating technology: CAR T cells can lead to even life-threatening off-tumor, on-target side effects if CAR T cells crossreact with healthy tissues. Here, we describe a novel modular universal CAR platform technology termed UniCAR that reduces the risk of on-target side effects by a rapid and reversible control of CAR T-cell reactivity. The UniCAR system consists of two components: (1) a CAR for an inert manipulation of T cells and (2) specific targeting modules (TMs) for redirecting UniCAR T cells in an individualized time- and target-dependent manner. UniCAR T cells can be armed against different tumor targets simply by replacement of the respective TM for (1) targeting more than one antigen simultaneously or subsequently to enhance efficacy and (2) reducing the risk for development of antigen-loss tumor variants under treatment. Here we provide ‘proof of concept’ for retargeting of UniCAR T cells to CD33- and/or CD123-positive acute myeloid leukemia blasts in vitro and in vivo .
Partial Prostatectomy for Anterior Cancer: Short-term Oncologic and Functional Outcomes
Authors: Arnauld Villers, Philippe Puech, Vincent Flamand, Georges-Pascal Haber, Mihir M. Desai, Sebastien Crouzet, Xavier Leroy, Sameer Chopra, Laurent Lemaitre, Adil Ouzzane, Inderbir S. Gill
Journal: European Urology (2016)
A Phase 1 -2 Study of Brentuximab Vedotin (Bv) and Bendamustine (B) in Patients with Relapsed or Refractory Hodgkin Lymphoma (HL) and Anaplastic Large T-Cell Lymphoma (ALCL)
Authors: Owen A. O'Connor, John Kuruvilla, Ahmed Sawas, Changchun Deng, Molly Patterson, Joseph M. Connors, Jennifer E Amengual, Michael Crump, Diego Villa
Journal: Blood (2014)
Abstract 3433: Identification of potential salivary response biomarkers in subjects practicing yogic breathing
Authors: Sundaravadivel Balasubramanian, Michael G. Janech, Graham W. Warren
Journal: Cancer Research (2015)

Abstract Yogic Breathing (YB; Pranayama) is a form of Yoga technique practiced since ancient times for healthy living. In the United States, the practice of Yoga has markedly increased in recent years. Recent data suggest that adjunctive Yoga in cancer patients may help patients with symptom management. Whereas there are data on Asana (Postures) that involve physical movements in cancer patients, there are limited data on YB. Considering the ease of practice when compared to Asana, YB might benefit patients who are already physically overwhelmed with symptom burden. Current data measure the outcomes of Yoga using subjective measures, but biomarkers in an easily accessible biospecimen might provide key information as to the effects of YB among practitioners. We hypothesized that YB stimulates alterations in the salivary biomarker expression. We conducted an Institutional Review Board approved pilot randomized controlled trial in 20 subjects (n = 10 in each group) to compare the salivary expression of biomarkers between a 20 min YB group vs. Attention Control (AC) group. The YB group performed two exercises (Pranava Pranayama, and Thirumoolar Pranayama) each for 10 min, and the AC group read a scientific article for the same amount of time. Tandem Mass Spectrometric (LC-LC-MS-MS), Multiplex, and Western blot analysis showed the differential expression of 22 salivary proteins associated with immune response, stress and cancer. As compared with the AC group, YB increased Deleted in Malignant Brain Tumor 1 (DMBT1) as early as 5 min and maintained significantly high levels in all time points tested. In contrast, YB reduced IL-1beta (at 10, 15 and 20 min) and IL-8 levels (at 5, 10, 15 and 20 min) in participants when compared to AC controls. Further analysis of salivary lipidomic profiles demonstrated marginal reductions in sphingosine and sphingosine-1-phosphate levels in YB group. Collectively, our data provide the first evidence that YB could alter salivary biomarkers associated with cancer, inflammation, and stress. These markers may be useful to evaluate symptom management via stress reduction and immune regulation. Citation Format: Sundaravadivel Balasubramanian, Michael G. Janech, Graham W. Warren. Identification of potential salivary response biomarkers in subjects practicing yogic breathing. [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 3433. doi:10.1158/1538-7445.AM2015-3433
Genome Wide Profiling Of Chromosomal Abnormalities In 37 Patients With Monoclonal Gammopathy Of Undetermined Significance (MGUS)
Authors: Aneta Mikulasova, Vladimira Vallova, Jan Smetana, Henrieta Greslikova, Renata Kupska, Michaela Purgertova, Lucie Rihova, Viera Sandecka, Ludek Pour, Miroslav Penka, Petr Kuglik, Roman Hajek
Journal: Blood (2013)
Atherosclerotic Vascular Disease Conference
Authors: David P. Faxon, Valentin Fuster, Peter Libby, Joshua A. Beckman, William R. Hiatt, Robert W. Thompson, James N. Topper, Brian H. Annex, John H. Rundback, Rosalind P. Fabunmi, Rose Marie Robertson, Joseph Loscalzo
Journal: Circulation (2004)
The economic and clinical burden of nonalcoholic fatty liver disease in the United States and Europe
Authors: Zobair M. Younossi, Deirdre Blissett, Robert Blissett, Linda Henry, Maria Stepanova, Youssef Younossi, Andrei Racila, Sharon Hunt, Rachel Beckerman
Journal: Hepatology (2016)

Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease. There is uncertainty around the economic burden of NAFLD. We constructed a steady-state prevalence model to quantify this burden in the United States and Europe. Five models were constructed to estimate the burden of NAFLD in the United States and four European countries. Models were built using a series of interlinked Markov chains, each representing age increments of the NAFLD and the general populations. Incidence and remission rates were calculated by calibrating against real-world prevalence rates. The data were validated using a computerized disease model called DisMod II. NAFLD patients transitioned between nine health states (nonalcoholic fatty liver, nonalcoholic steatohepatitis [NASH], NASH-fibrosis, NASH-compensated cirrhosis, NASH-decompensated cirrhosis, hepatocellular carcinoma, liver transplantation, post-liver transplant, and death). Transition probabilities were sourced from the literature and calibrated against real-world data. Utilities were obtained from NAFLD patients using the Short Form-6D. Costs were sourced from the literature and local fee schedules. In the United States, over 64 million people are projected to have NAFLD, with annual direct medical costs of about $103 billion ($1,613 per patient). In the Europe-4 countries (Germany, France, Italy, and United Kingdom), there are ∼52 million people with NAFLD with an annual cost of about €35 billion (from €354 to €1,163 per patient). Costs are highest in patients aged 45-65. The burden is significantly higher when societal costs are included.The analysis quantifies the enormity of the clinical and economic burdens of NAFLD, which will likely increase as the incidence of NAFLD continues to rise. (Hepatology 2016;64:1577-1586).
Activity of crizotinib (C) in patients (pts) with clear cell sarcoma (CCSA) in EORTC phase II trial 90101 "CREATE".
Authors: Patrick Schoffski, Agnieszka Wozniak, Silvia Stacchiotti, Piotr Rutkowski, Maria Debiec-Rychter, Raf Sciot, Jean-Yves Blay, Lars Lindner, Sandra J. Strauss, David Alan Anthoney, Michael Gordon Leahy, Peter Reichardt, Sandrine Marreaud, Sandra Collette, Jonathan Steuve, Tiana Raveloarivahy, Sebastian Bauer
Journal: Journal of Clinical Oncology (2015)

10542 Background: This phase II trial assesses the safety and activity of the ALK/MET inhibitor C in 6 different ALK- or MET-driven tumor types including CCSA, an orphan, treatment-refractory malignancy. The chimeric EWS-ATF1 and EWSR1/CREB1 fusion genes are hallmarks of CCSA and activate MET through the melanocyte master transcription factor. Methods: Pts with local diagnosis of advanced/metastatic CCSA consented for shipment of a non-returnable tumor tissue block and were screened for trial participation after central confirmation of the diagnosis and Vysis EWSR1 break apart FISH (Abbot Molecular). Eligible pts received C 250 mg twice daily p.o. A Simon's optimal two stage design was implemented independently in each disease-specific study cohort. If at least 2 out of the first 12 MET+, eligible and evaluable CCSA pts achieved a confirmed RECIST 1.1 PR or CR, a maximum of 35 pts were to be enrolled and treated to assess the activity of C, with no interruption of recruitment planned between the two stages. The abstract presents CCSA enrollment characteristics and activity according to the Simon's design stopping rule. Updated activity/safety results of the fully recruited cohort will be available at ASCO. Results: Between 01/2013 and 12/2014, 16 investigational sites in 8 European countries recruited 43 pts, of whom 32 had a centrally confirmed diagnosis of MET+ CCSA (tissue blocks available from 97.7% of pts). Central histological and molecular work-up took a mean lab turnaround time of 4 days (range, 2-10) after receipt of unstained slides. Among the first 12 eligible and evaluable MET+ cases, no RECIST responses were observed; best response was SD in 7 and PD in 5 pts. The mean duration of treatment was 6-7 cycles (range, 2-14; cycle length 3 weeks). Conclusions: EORTC is able to perform molecularly driven screening phase II trials in orphan malignancies with mandatory collection of tumor tissue and real time confirmation of diagnosis and genetic profiling. C did not meet pre-specified response rates in MET+ CCSA, but achieved long-lasting disease control in a clinically relevant subset of pts, which prompted ongoing correlative studies using available tissue, genetic and clinical data. Clinical trial information: NCT01524926.