tbuckley/cabot-search huggingface dataset:
Altered DNA Methylation of Long Noncoding RNA <i>H19</i> in Calcific Aortic Valve Disease Promotes Mineralization by Silencing <i>NOTCH1</i>
Authors: Fayez Hadji, Marie-Chloé Boulanger, Simon-Pierre Guay, Nathalie Gaudreault, Soumiya Amellah, Guada Mkannez, Rihab Bouchareb, Joël Tremblay Marchand, Mohamed Jalloul Nsaibia, Sandra Guauque-Olarte, Philippe Pibarot, Luigi Bouchard, Yohan Bossé, Patrick Mathieu
Journal: Circulation (2016)

Calcific aortic valve disease is characterized by an abnormal mineralization of the aortic valve. Osteogenic activity in the aortic valve is under the control of NOTCH1, which regulates the expression of key pro-osteogenic genes such as RUNX2 and BMP2. Long noncoding RNAs (lncRNAs) may reprogram cells by altering the gene expression pattern.Multidimensional genomic profiling was performed in human aortic valves to document the expression of lncRNAs and the DNA methylation pattern in calcific aortic valve disease. In-depth functional assays were carried out to document the impact of lncRNA on the mineralization of the aortic valve.We documented that lncRNA H19 (H19) was increased in calcific aortic valve disease. Hypomethylation of the promoter region was observed in mineralized aortic valves and was inversely associated with H19 expression. Knockdown and overexpression experiments showed that H19 induces a strong osteogenic phenotype by altering the NOTCH1 pathway. Gene promoter analyses showed that H19 silenced NOTCH1 by preventing the recruitment of p53 to its promoter. A knockdown of H19 in valve interstitial cells (VICs) increased the expression of NOTCH1 and decreased the level of RUNX2 and BMP2, 2 downstream targets repressed by NOTCH1. In rescue experiments, the transfection of a vector encoding for the active Notch intracellular domain prevented H19-induced mineralization of valve interstitial cells.These findings indicate that a dysregulation of DNA methylation in the promoter of H19 during calcific aortic valve disease is associated with a higher expression of this lncRNA, which promotes an osteogenic program by interfering with the expression of NOTCH1.
Abstract 3682: Enhanced anticancer effect of 5-fluorouracil loaded into thermoresponsive conjugated linoleic acid-incorporated poloxamer hydrogel on metastastic colon cancer models
Authors: Woo Kyun Bae, Ji Hee Lee, Myong Suk Park, Jun Eul Hwang, Hyun Jeong Shim, Sang Hee Cho, Ding-Ding Guo, Chong Su Cho, Sang Joon Lee, In Kyu Park, Ik Joo Chung
Journal: Cancer Research (2010)

Abstract Background: 5-Fluorouracil (5-FU) is a useful chemotherapeutic agent in the treatment of solid tumors. However, it is very short half-life in plasma circulation greatly limited the in vivo antitumor efficacy, and intravenous 5FU injection is unlikely to achieve optimal dose effectiveness within peritoneal cavity. Conjugated linoleic acid-coupled Pluronic F127 (Plu-CLA) is an effective drug delivery system with numerous advantages and has an anticancer activity. It was also shown that paclitaxel loaded in Plu-CLA demonstrated synergistic tumor suppression through robust cell cycle arrest and enhanced apoptosis in tumor compared to paclitaxel in poloxamer hydrogel. The aim of this work is to evaluate the therapeutic efficacy of Plu-CLA as a new intraperitoneal 5FU delivery system. Methods: Cytotoxicity was evaluated by using CT-26 murine colon carcinoma cell. We established peritoneal metastasis models and hepatic metastasis models for colon cancer using BALB/c mice and firefly luciferase-expressing CT-26 (CT26/Fluc) cells. Tumor progression and response to therapy were monitored by bioluminescence imaging (BLI). Results: MTT assay indicated that 5-FU loaded in Plu-CLA hydrogel (P-FU) could increase the cytotoxic activity of 5-FU in CT-26. P-FU significantly enhanced apoptosis compared with 5-FU control. It was found that Caspase 3 and p21 were up-regulated, whereas Bcl-2 was down-regulated. Moreover, growth of hepatic metastases in vivo was significantly reduced in mice treated with P-FU. Treatment with P-FU substantially delayed tumor growth of intraperitoneal metastasis greatly and tumor-bearing mice treated with P-FU showed a better survival tendency than the 5-FU alone. Conclusion: These results were attributed to the synergistic effect of Plu-CLA. 5-FU administered in Plu-CLA hydrogel led to significant enhancement of tumor growth suppression and cellular apoptosis. Therefore, Plu-CLA could be a potential intraperitoneal carrier for hydrophilic 5-FU for the effective treatment of metastatic colon cancer. . Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3682.
Predictive Value of Clonality Assays in Patients With Non-Hodgkin's Lymphoma Undergoing Autologous Bone Marrow Transplant: A Single Institution Study
Authors: Sara Mach-Pascual, Robert D. Legare, Doanh Lu, Mary Kroon, Donna Neuberg, Ramana Tantravahi, Richard M. Stone, Arnold S. Freedman, Lee M. Nadler, John G. Gribben, D. Gary Gilliland
Journal: Blood (1998)
Patterns of care regarding adjuvant hormonal agents and treatment of bone health in postmenopausal women with breast cancer in community and academic centers before and after the availability of ATAC (Adjuvant Tamoxifen, Armidex or Combination) study
Authors: M. K. Tummala, M. Wajahath, M. Kotlarewsky, A. Aggarwal, D. Muller, M. C. Liu, W. P. McGuire, Y. Ottaviano
Journal: Journal of Clinical Oncology (2007)

6621 Background: Results from the ATAC trial comparing Tamoxifen to the Aromatase inhibitors (AIs) anastrozole in PM women with early stage breast cancer were initially presented in San Antonio, Texas, in December 2001. ASCO issued guidelines for the adjuvant use of AIs in 2002, updated in 2003. We compared patterns of usage of adjuvant hormonal agents and bone health management before and after availability of the ATAC data in community versus academic centers. Methods: We conducted a retrospective analysis of 432 patients between 1999–2005 from group practices affiliated with two large community hospitals and one academic center. Data were collected from tumor registries regarding demographics, first-line hormonal agent choice, and use of bone density studies, vitamin D/calcium supplements and bisphosphonates. Results: Demographics were identical in both groups before and after January 2002. Before 2002, 96% of the patients were prescribed Tamoxifen in both community and academic centers. After the initial presentation of the ATAC data, 55.08% (65/118) of patients from the community centers versus only 17.11% (19/111) from the academic center were prescribed AIs (p=0.0001). Of the 84 patients who received an AI after January 2002, similar proportions of patients had baseline bone density scans (38.5% community vs. 36.8% academic; p=0.89) and follow up annual/biannual scans (33 % vs. 32%; p=0.85). In addition, similar proportions of patients on AIs were prescribed calcium/vitamin D supplements (47.4% vs. 52.6%; p=0.69) and bisphosphonates (36.8% vs. 21.05%; p=0.20) in community and academic centers, respectively. Conclusions: Community oncologists adopted AIs into clinical practice sooner than academic physicians on the basis of unpublished clinical trial results, even before ASCO published guidelines. Although patients on AIs are deemed to be at higher risk for bone fractures, fewer than 40% were evaluated with baseline or surveillance bone density scans in both community and academic practices. Similar proportions of patients received calcium/vitamin D supplements or bisphosphonates among centers. No significant financial relationships to disclose.
TCT-769 Ultrasound-assisted Catheter-Directed Thrombolysis in the Treatment of High Risk Pulmonary Embolism: A Meta-analysis
Authors: Georges El Hayek, Michael McDaniel, Henry Liberman, Chandan Devireddy, Pete Fong, Gautam Kumar, Wissam Jaber
Journal: Journal of the American College of Cardiology (2016)
TCT-73 Serial Three-Vessel Optical Coherence Tomography and Intravascular Ultrasound Analysis of Changing Morphologies Associated of Plaque Progression in Patients With Stable Angina Pectoris
Authors: Myong Hwa Yamamoto, Kennosuke Yamashita, Mitsuaki Matsumura, Seitarou Ebara, Toshitaka Okabe, Shigeo Saito, Koichi Hoshimoto, Kisaki Amemiya, Tadayuki Yakushiji, Naoei Isomura, Hiroshi Araki, Chiaki Obara, Masahiko Ochiai, Gary Mintz, Akiko Maehara
Journal: Journal of the American College of Cardiology (2016)
Interferon lambda 4 expression is suppressed by the host during viral infection
Authors: MeeAe Hong, Johannes Schwerk, Chrissie Lim, Alison Kell, Abigail Jarret, Joseph Pangallo, Yueh-Ming Loo, Shuanghu Liu, Curt H. Hagedorn, Michael Gale, Ram Savan
Journal: The Journal of Experimental Medicine (2016)

Interferon (IFN) lambdas are critical antiviral effectors in hepatic and mucosal infections. Although IFNλ1, IFNλ2, and IFNλ3 act antiviral, genetic association studies have shown that expression of the recently discovered IFNL4 is detrimental to hepatitis C virus (HCV) infection through a yet unknown mechanism. Intriguingly, human IFNL4 harbors a genetic variant that introduces a premature stop codon. We performed a molecular and biochemical characterization of IFNλ4 to determine its role and regulation of expression. We found that IFNλ4 exhibits similar antiviral activity to IFNλ3 without negatively affecting antiviral IFN activity or cell survival. We show that humans deploy several mechanisms to limit expression of functional IFNλ4 through noncoding splice variants and nonfunctional protein isoforms. Furthermore, protein-coding IFNL4 mRNA are not loaded onto polyribosomes and lack a strong polyadenylation signal, resulting in poor translation efficiency. This study provides mechanistic evidence that humans suppress IFNλ4 expression, suggesting that immune function is dependent on other IFNL family members.
Weekly paclitaxel, oxaliplatin, 5-FU and leucovorin in the treatment of metastatic pancreatic cancer
Authors: B. Chue, N. Chen
Journal: Journal of Clinical Oncology (2006)

14146 Background: Patients with metastatic PC have poor prognosis due to lack of effective treatment options. We did a pilot study on weekly chemotherapy with TOFL in the treatment of patients with advanced PC associated with severe clinical symptoms. Methods: 4 patients age 35 to 56 with biopsy proven metastatic PC were treated with weekly T: 50 mg/m 2 , O: 60 mg/m 2 , L: 20 mg/m 2 and F: 425 mg/m 2 . One patient (A.B.) also received intermittent Cetuximab. Pre-medication with I.V. Glutathione and calcium magnesium was routinely used to prevent Oxaliplatin-related sensory neuropathy. Patients were seen every week. Sequential CA19–9 levels and CT scans were obtained for followup. Results: After 12 weeks of treatments, all 4 patients had dramatic reduction of CA 19–9 levels (see table) and improvement of cancer-related symptoms. 3 patients now have normalization of CA19–9 levels. Patient D.P. had bilirubin of 27 and severe abdominal pain after disease progression following first-line chemotherapy. His bilirubin returned to normal range and abdominal pain resolved after 6 weeks on the protocol. Patient A.B. was severely debilitated (ECOG 4) following progression of disease after 2 prior lines of chemotherapy. He is now alive over a year with PR and ECOG 1. Patient L.C. presented with bilirubin of 9.6, nausea and abdominal pain. Her total bilirubin normalized and GI symptoms resolved after 12 weeks. Patient I.S. had disease progression with liver metastasis and worsening abdominal pain after failing 2 lines of prior chemotherapy. Her CA 19–9 decreased by over 80% and abdominal pain resolved after 12 weeks. The regimen was well tolerated with only one grade 3 neurotoxicity. Conclusions: Weekly combination of Paclitaxel, Oxaliplatin, 5-Fu and Leucovorin has significant activity against advanced PC with manageable side effects. Phase II study is underway. [Table: see text] No significant financial relationships to disclose.
Expression of Long Interspersed Nuclear Element 1 Retroelements and Induction of Type I Interferon in Patients With Systemic Autoimmune Disease
Authors: Clio P. Mavragani, Irina Sagalovskiy, Qiu Guo, Adrianos Nezos, Efstathia K. Kapsogeorgou, Pin Lu, Jun Liang Zhou, Kyriakos A. Kirou, Surya V. Seshan, Haralampos M. Moutsopoulos, Mary K. Crow
Journal: Arthritis & Rheumatology (2016)

Increased expression of type I interferon (IFN) and a broad signature of type I IFN-induced gene transcripts are observed in patients with systemic lupus erythematosus (SLE) and other systemic autoimmune diseases. To identify disease-relevant triggers of the type I IFN pathway, this study sought to investigate whether endogenous virus-like genomic repeat elements, normally silent, are expressed in patients with systemic autoimmune disease, and whether these retroelements could activate an innate immune response and induce type I IFN.Expression of type I IFN and long interspersed nuclear element 1 (LINE-1; L1) was studied by polymerase chain reaction, Western blotting, and immunohistochemistry in samples of kidney tissue from patients with lupus nephritis and minor salivary gland (MSG) tissue from patients with primary Sjögren's syndrome (SS). Induction of type I IFN by L1 was investigated by transfection of plasmacytoid dendritic cells (PDCs) or monocytes with an L1-encoding plasmid or L1 RNA. Involvement of innate immune pathways and altered L1 methylation were assessed.Levels of L1 messenger RNA transcripts were increased in lupus nephritis kidneys and in MSG tissue from patients with SS. Transcript expression correlated with the expression of type I IFN and L1 DNA demethylation. L1 open-reading frame 1/p40 protein and IFNβ were expressed in MSG ductal epithelial cells and in lupus nephritis kidneys, and IFNα was detected in infiltrating PDCs. Transfection of PDCs or monocytes with L1-encoding DNA or RNA induced type I IFN. Inhibition of Toll-like receptor 7 (TLR-7)/TLR-8 reduced the induction of IFNα by L1 in PDCs, and an inhibitor of IKKε/TANK-binding kinase 1 abrogated the induction of type I IFN by L1 RNA in monocytes.L1 genomic repeat elements represent endogenous nucleic acid triggers of the type I IFN pathway in SLE and SS and may contribute to initiation or amplification of autoimmune disease.
Highlights in Hematologic Malignancy Treatments
Authors: Joseph G. Jurcic
Journal: JAMA Oncology (2016)

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 Oncology HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Oncology journal
Diagnosis of Invasive Fungal Infections by a Real-Time Panfungal PCR Assay in Pediatric Patients Undergoing Intensive Chemotherapy or Allogeneic Stem Cell Transplantion.
Authors: Christine Landlinger, Lenka Baskova, Sandra Preuner, Martine Van Grotel, Nico G. Hartwig, Marry M. van den Heuvel, Thomas Lion
Journal: Blood (2009)
TCT-815 Clinical benefits of less-invasive, device–based Left Ventricular Reconstruction: A hybrid option for patients with ischemic cardiomyopathy
Authors: Christoph Schmitz, Mauri Biffi, Horst Sievert, Petr Neuzil, Salvatore Brugaletta, Christian Frerker, Azfar Zaman, Luigi Fiocca, Louis Labrousse, Lon Annest
Journal: Journal of the American College of Cardiology (2016)
Early Molecular Response Is Predictive Of Overall, Progression-Free and Event-Free Survival In Chronic Myeloid Leukemia Using Second-Generation Tyrosine Kinase Inhibitors After Imatinib Treatment
Authors: Beatriz F Ribeiro, Bruna Vergilio, Eliana C M Miranda, Maria Helena Almeida, Marcia Torresan Delamain, Rosana A Silveira, Carmino A De Souza, Dulcinéia Martins Albuquerque, Andrey dos Santos, Irene Lorand-Metze, Vagner O Duarte, Gislaine O. Duarte, Katia B. Pagnano
Journal: Blood (2013)
Brief Report: The Role of Rare Protein‐Coding Variants in Anti–Tumor Necrosis Factor Treatment Response in Rheumatoid Arthritis
Authors: Jing Cui, Dorothee Diogo, Eli A. Stahl, Helena Canhao, Xavier Mariette, Jeffrey D. Greenberg, Yukinori Okada, Dimitrios A. Pappas, Robert S. Fulton, Paul P. Tak, Michael T. Nurmohamed, Annette Lee, David E. Larson, Fina Kurreeman, Tracie L. Deluca, Michelle O'Laughlin, Catrina C. Fronick, Lucinda L. Fulton, Elaine R. Mardis, Irene E. van der Horst‐Bruinsma, Gert‐Jan Wolbink, Peter K. Gregersen, Joel M. Kremer, J. Bart A. Crusius, Niek de Vries, Tom W. J. Huizinga, João Eurico Fonseca, Corinne Miceli‐Richard, Elizabeth W. Karlson, Marieke J. H. Coenen, Anne Barton, Robert M. Plenge, Soumya Raychaudhuri
Journal: Arthritis & Rheumatology (2016)

Objective In many rheumatoid arthritis (RA) patients, disease is controlled with anti–tumor necrosis factor (anti‐TNF) biologic therapies. However, in a significant number of patients, the disease fails to respond to anti‐TNF therapy. We undertook the present study to examine the hypothesis that rare and low‐frequency genetic variants might influence response to anti‐TNF treatment. Methods We sequenced the coding region of 750 genes in 1,094 RA patients of European ancestry who were treated with anti‐TNF. After quality control, 690 genes were included in the analysis. We applied single‐variant association and gene‐based association tests to identify variants associated with anti‐TNF treatment response. In addition, given the key mechanistic role of TNF, we performed gene set analyses of 27 TNF pathway genes. Results We identified 14,420 functional variants, of which 6,934 were predicted as nonsynonymous 2,136 of which were further predicted to be “damaging.” Despite the fact that the study was well powered, no single variant or gene showed study‐wide significant association with change in the outcome measures disease activity or European League Against Rheumatism response. Intriguingly, we observed 3 genes, of 27 with nominal signals of association ( P &lt; 0.05), that were involved in the TNF signaling pathway. However, when we performed a rigorous gene set enrichment analysis based on association P value ranking, we observed no evidence of enrichment of association at genes involved in the TNF pathway ( P enrichment = 0.15, based on phenotype permutations). Conclusion Our findings suggest that rare and low‐frequency protein‐coding variants in TNF signaling pathway genes or other genes do not contribute substantially to anti‐TNF treatment response in patients with RA.
The transcription factor GLI2 as a downstream mediator of transforming growth factor-β-induced fibroblast activation in SSc
Authors: Ruifang Liang, Barbora Šumová, Cinzia Cordazzo, Tatjana Mallano, Yun Zhang, Thomas Wohlfahrt, Clara Dees, Andreas Ramming, Dorota Krasowska, Małgorzata Michalska-Jakubus, Oliver Distler, Georg Schett, Ladislav Šenolt, Jörg H W Distler
Journal: Annals of the Rheumatic Diseases (2016)

Hedgehog signalling plays a critical role during the pathogenesis of fibrosis in systemic sclerosis (SSc). Besides canonical hedgehog signalling with smoothened (SMO)-dependent activation of GLI transcription factors, GLI can be activated independently of classical hedgehog ligands and receptors (so-called non-canonical pathways). Here, we aimed to evaluate the role of non-canonical hedgehog signalling in SSc and to test the efficacy of direct GLI inhibitors that target simultaneously canonical and non-canonical hedgehog pathways.The GLI inhibitor GANT-61 was used to inhibit canonical as well as non-canonical hedgehog signalling, while the SMO inhibitor vismodegib was used to selectively target canonical hedgehog signalling. Furthermore, GLI2 was selectively depleted in fibroblasts using the Cre-LoxP system. The effects of pharmacological or genetic of GLI2 on transforming growth factor-β (TGF-β) signalling were analysed in cultured fibroblasts, in bleomycin-induced pulmonary fibrosis and in mice with overexpression of a constitutively active TGF-β receptor I.TGF-β upregulated GLI2 in a Smad3-dependent manner and induced nuclear accumulation and DNA binding of GLI2. Fibroblast-specific knockout of GLI2 protected mice from TBRact-induced fibrosis. Combined targeting of canonical and non-canonical hedgehog signalling with direct GLI inhibitors exerted more potent antifibrotic effects than selective targeting of canonical hedgehog signalling with SMO inhibitors in experimental dermal and pulmonary fibrosis.Our data demonstrate that hedgehog pathways and TGF-β signalling both converge to GLI2 and that GLI2 integrates those signalling to promote tissue fibrosis. These findings may have translational implications as non-selective inhibitors of GLI2 are in clinical use and selective molecules are currently in development.
Hyperthermia-triggered drug delivery from iRGD-modified temperature-sensitive liposomes enhances the anti-tumor efficacy using high intensity focused ultrasound
Authors: Zhiting Deng, Yang Xiao, Min Pan, Fei Li, Wanlu Duan, Long Meng, Xin Liu, Fei Yan, Hairong Zheng
Journal: Journal of Controlled Release (2016)
EFICACIA Y SEGURIDAD DE PRÓTESIS METÁLICAS DE APOSICIÓN LUMINAL EN EL TRATAMIENTO DE ESTENOSIS BENIGNAS DEL TRACTO DIGESTIVO
Authors: J Santos Fernández, A Figueroa, C Chavarría, R Torres Yuste, M Cimavilla Román, P Gil Simón, R Sanchez-Ocaña Hernández, I Peñas Herrero, C De La Serna Higuera, M Pérez-Miranda Castillo
Journal: Endoscopy (2016)

Las perforaciones y estenosis gastrointestinales pueden ser tratadas con prótesis metálicas auto-expandibles (PMAC), aunque la migración limita la eficacia. Ahora tenemos disponibles las prótesis metálicas de aposición luminal (LAMS) que son utilizadas para el tratamiento de quistes pancreáticos. La utilización intraluminal de éstas, puede mejorar los síntomas en casos seleccionados que fallan al tratamiento con las prótesis metálicas clásicas.
General practice is making a leap in the dark
Authors: Martin Marshall, Denis Pereira Gray
Journal: BMJ (2016)

New models of working risk throwing the baby out with the bathwater 

A strong case is being made in many countries that the traditional model of general practice needs to change. Critics claim that practices are too small and too isolated, that they are increasingly unable to meet their patients’ needs and expectations, and are unfit to lead the necessary redesign of health systems.1 2 As general practice in the UK in particular struggles with a demoralised workforce and inadequate resources,3 these criticisms are being taken on board. Quietly but rapidly, and in a largely ad hoc fashion, general practice is changing; small practices are closing or merging with other practices, practice networks are forming, the primary care workforce is becoming increasingly multidisciplinary, and new integrated models of care that bring together community and hospital based services are being developed.

Many of these changes may be good for patients and for the health system, but insufficient attention is being paid to the possible unintended consequences. One substantial risk should …