tbuckley/cabot-search huggingface dataset:
Incidence and implications of HER2 and hormonal receptor overexpression in newly diagnosed metastatic breast cancer (MBC)
Authors: F. Penault-Llorca, A. Vincent-Salomon, M. C. Mathieu, V. Trillet-Lenoir, D. Khayat, M. Marty
Journal: Journal of Clinical Oncology (2005)

764 Background: Overexpression of the HER2 receptor protein predicts a worse prognosis and higher metastatic risk in patients (pts) with breast cancer. HER2 positivity also has a strong predictive value for the clinical benefit of trastuzumab (Herceptin, H). The aim of this study was to assess the incidence of HER2 and ER/PR overexpression in patients with newly diagnosed metastatic breast cancer (MBC) and to compare the characteristics and outcomes of pts with HER2-positive and HER2-negative disease. Methods: From June 2000 to November 2001, 96 centres in France participated in a prospective epidemiological study including 741 consecutive pts with newly diagnosed MBC. HER2 and hormonal receptor overexpression was assessed by immunohistochemistry (IHC). Results: Of the 699 evaluable pts aged 25 to 83 (median 54.6) years, 67% were postmenopausal. Tumour characteristics: 29.6% were HER2 3+ by IHC; 61.4% were ER+, and 66.6% either ER+ or PR+. Notably, 22.4% of ER+ and 21.3% of PR+ tumours were also HER2 IHC 3+; furthermore, 23% of ER+ and PR+ tumours showed IHC 3+ staining for HER2. HER2 overexpression was more frequent in invasive ductal carcinoma than in invasive lobular carcinoma (32.1% vs 16.5%; p=0.0033, OR=2.4), and was associated with a shorter time to relapse (p=0.0294). Tumour grade: 92% were SBR grade 2 or 3. 70% had nodal involvement and 32% relapsed within 6 months of MBC diagnosis. However, HER2 overexpression was associated with neither SBR grade nor nodal involvement. Conclusions: These findings confirm that initial HER2 overexpression at presentation is frequent in MBC (close to 30% as assessed by IHC 3+ staining) and is associated with a shorter time to relapse than HER2-negative disease. Importantly, nearly a quarter (22.4%) of ER+ tumours in MBC were also HER2+. This significant group of patients could possibly benefit from the addition of trastuzumab to their treatment. No significant financial relationships to disclose.
Lysophosphatidylcholine acyltransferase 1 is downregulated by hepatitis C virus: impact on production of lipo-viro-particles
Authors: Frauke Beilstein, Matthieu Lemasson, Véronique Pène, Dominique Rainteau, Sylvie Demignot, Arielle R Rosenberg
Journal: Gut (2016)

Objective HCV is intimately linked with the liver lipid metabolism, devoted to the efflux of triacylglycerols stored in lipid droplets (LDs) in the form of triacylglycerol-rich very-low-density lipoproteins (VLDLs): (i) the most infectious HCV particles are those of lowest density due to association with triacylglycerol-rich lipoproteins and (ii) HCV-infected patients frequently develop hepatic steatosis (increased triacylglycerol storage). The recent identification of lysophosphatidylcholine acyltransferase 1 (LPCAT1) as an LD phospholipid-remodelling enzyme prompted us to investigate its role in liver lipid metabolism and HCV infectious cycle. Design Huh-7.5.1 cells and primary human hepatocytes (PHHs) were infected with JFH1-HCV. LPCAT1 depletion was achieved by RNA interference. Cells were monitored for LPCAT1 expression, lipid metabolism and HCV production and infectivity. The density of viral particles was assessed by isopycnic ultracentrifugation. Results Upon HCV infection, both Huh-7.5.1 cells and PHH had decreased levels of LPCAT1 transcript and protein, consistent with transcriptional downregulation. LPCAT1 depletion in either naive or infected Huh-7.5.1 cells resulted in altered lipid metabolism characterised by LD remodelling, increased triacylglycerol storage and increased secretion of VLDL. In infected Huh-7.5.1 cells or PHH, LPCAT1 depletion increased production of the viral particles of lowest density and highest infectivity. Conclusions We have identified LPCAT1 as a modulator of liver lipid metabolism downregulated by HCV, which appears as a viral strategy to increase the triacylglycerol content and hence infectivity of viral particles. Targeting this metabolic pathway may represent an attractive therapeutic approach to reduce both the viral titre and hepatic steatosis.
Subgenome parallel selection is associated with morphotype diversification and convergent crop domestication in Brassica rapa and Brassica oleracea
Authors: Feng Cheng, Rifei Sun, Xilin Hou, Hongkun Zheng, Fenglan Zhang, Yangyong Zhang, Bo Liu, Jianli Liang, Mu Zhuang, Yunxia Liu, Dongyuan Liu, Xiaobo Wang, Pingxia Li, Yumei Liu, Ke Lin, Johan Bucher, Ningwen Zhang, Yan Wang, Hui Wang, Jie Deng, Yongcui Liao, Keyun Wei, Xueming Zhang, Lixia Fu, Yunyan Hu, Jisheng Liu, Chengcheng Cai, Shujiang Zhang, Shifan Zhang, Fei Li, Hui Zhang, Jifang Zhang, Ning Guo, Zhiyuan Liu, Jin Liu, Chao Sun, Yuan Ma, Haijiao Zhang, Yang Cui, Micheal R Freeling, Theo Borm, Guusje Bonnema, Jian Wu, Xiaowu Wang
Journal: Nature Genetics (2016)
Efficacy of Folic Acid Therapy on the Progression of Chronic Kidney Disease
Authors: Xin Xu, Xianhui Qin, Youbao Li, Danhua Sun, Jun Wang, Min Liang, Binyan Wang, Yong Huo, Fan Fan Hou
Journal: JAMA Internal Medicine (2016)

<h3>Importance</h3> The efficacy of folic acid therapy on renal outcomes has not been previously investigated in populations without folic acid fortification. <h3>Objective</h3> To test whether treatment with enalapril and folic acid is more effective in slowing renal function decline than enalapril alone across a spectrum of renal function at baseline from normal to moderate chronic kidney disease (CKD) among Chinese adults with hypertension. <h3>Design, Setting, and Participants</h3> In this substudy of eligible China Stroke Primary Prevention Trial (CSPPT), 15 104 participants with an estimated glomerular filtration rate (eGFR) 30 mL/min/1.73 m<sup>2</sup>or greater, including 1671 patients with CKD, were recruited from 20 communities in Jiangsu province in China. <h3>Interventions</h3> Participants were randomized to receive a single tablet daily containing 10 mg enalapril and 0.8 mg folic acid (n = 7545) or 10 mg enalapril alone (n = 7559). <h3>Main Outcomes and Measures</h3> The primary outcome was the progression of CKD, defined as a decrease in eGFR of 30% or more and to a level of less than 60 mL/min/1.73 m<sup>2</sup>if the baseline eGFR was 60 mL/min/1.73 m<sup>2</sup>or more, or a decrease in eGFR of 50% or more if the baseline eGFR was less than 60 mL/min/1.73 m<sup>2</sup>; or end-stage renal disease. Secondary outcomes included a composite of the primary outcome and all-cause death, rapid decline in renal function, and rate of eGFR decline. <h3>Results</h3> Overall, 15 104 Chinese adults with a mean (range) age of 60 (45-75) years were recruited; median follow-up was 4.4 years. There were 164 and 132 primary events in the enalapril group and the enalapril–folic acid group, respectively. Compared with the enalapril group, the enalapril–folic acid group had a 21% reduction in the odds of the primary event (odds ratio [OR], 0.79; 95% CI, 0.62-1.00) and a slower rate of eGFR decline (1.28% vs 1.42% per year;<i>P</i> = .02). Among the participants with CKD at baseline, folic acid therapy resulted in a significant reduction in the risks for the primary event (OR, 0.44; 95% CI, 0.26-0.75), rapid decline in renal function (OR, 0.67; 95% CI, 0.47-0.96) and the composite event (OR, 0.62; 95% CI, 0.43-0.90), and a 44% slower decline in renal function (0.96% vs 1.72% per year,<i>P</i> &lt; .001). Among those without CKD at baseline, there was no between-group difference in the primary end point. <h3>Conclusions and Relevance</h3> Enalapril–folic acid therapy, compared with enalapril alone, can significantly delay the progression of CKD among patients with mild-to-moderate CKD. <h3>Trial Registration</h3> clinicaltrials.gov Identifier:NCT00794885
Lipoprotein(a) and Risk of Myocardial Infarction
Authors: Michael M. Ritter
Journal: JAMA (1994)

To the Editor.  —The article by Ridker et al 1 describing similar Lp(a) concentrations in patients with MI and matched controls is very welcome since prospective studies on this subject are sparse. 2,3 In the article and in the accompanying Editorial, 4 some possible reasons for the discrepant results compared with numerous (retrospective) studies are listed, but we would like to draw the attention to two further aspects.  Despite similar apo(a) isoform and phenotype distribution we were able to detect 53% lower Lp(a) concentrations in patients with hypertriglyceridemia (>12.93 mmol/L [500 mg/ dL], n=147) compared with controls (n=404, P  r =-0.22, P  5 In the study by Ridker et al, triglyceride concentrations are not given, but the cases had markedly lower high-density lipoprotein (HDL) cholesterol values compared with the controls. Because of the known negative correlation, this
Upstream regulators of hepatic Wnt/β‐catenin activity control liver metabolic zonation, development, and regeneration
Authors: Laure‐Alix Clerbaux, Rita Manco, Isabelle Leclercq
Journal: Hepatology (2016)

Clerbaux, Laure‐Alix Ph.D.; Manco, Rita M.Sc.; Leclercq, Isabelle M.D., Ph.D. Author Information
Confirmation of the Mantle Cell Lymphoma International Prognostic Index (MIPI) in An Independent Prospective Patient Cohort.
Authors: Eva Hoster, Joerg Hasford, Olivier Hermine, Hanneke C. Kluin-Nelemans, Jan Walewski, Marek Trneny, Christian H. Geisler, Vincent Ribrag, Achiel Van Hoof, Wolfram Klapper, Wolfgang Hiddemann, Martin H. Dreyling, Michael Unterhalt
Journal: Blood (2009)
Toxic Unbound Iron and Membrane Injury in b-Thalassemia and Sickle Cell Disease: Elevated Non-Transferrin Bound Iron (NTBI) and Malondialdehyde (MDA).
Authors: Patrick B. Walter, Ellen Fung, David W. Killilea, Qing Jiang, Bruce N. Ames, Jacqueline Madden, Ellen Butensky, John Porter, Patricia Evans, Paul Harmatz, Elliott P. Vichinsky
Journal: Blood (2004)
Genome-wide association study on the FEV 1 /FVC ratio in never-smokers identifies HHIP and FAM13A
Authors: Diana A. van der Plaat, Kim de Jong, Lies Lahousse, Alen Faiz, Judith M. Vonk, Cleo C. van Diemen, Ivana Nedeljkovic, Najaf Amin, Guy G. Brusselle, Albert Hofman, Corry-Anke Brandsma, Yohan Bossé, Don D. Sin, David C. Nickle, Cornelia M. van Duijn, Dirkje S. Postma, H. Marike Boezen
Journal: Journal of Allergy and Clinical Immunology (2016)
Faisabilité des coloscopies avec analgésie par un Mélange Equimolaire d'Oxygène et de Protoxyde d'Azote
Authors: A Vidal, J Steffann, F Carbonnel
Journal: Endoscopy (2005)

L'analgésie par un Mélange Equimolaire d'Oxygène et de Protoxyde d'Azote (MEOPA) est utilisée dans les services d'urgence lors des gestes douloureux, notamment pour des enfants. Quel peut être l'apport de cette méthode pour améliorer la tolérance à la coloscopie?
Prediction of High and Low-Risk Multiple Myeloma Based on the EMC92 Gene Expression Signature and the International Staging System
Authors: Rowan Kuiper, Martin H. Van Vliet, Erik H. van Beers, Annemiek Broijl, George Mulligan, Hervé Avet-Loiseau, Walter Gregory, Gareth J. Morgan, Hartmut Goldschmidt, Henk Lokhorst, Mark van Duin, Pieter Sonneveld
Journal: Blood (2014)
Pioglitazone vs Glimepiride and Carotid Intima-Media Thickness
Authors: Dario Giugliano, Katherine Esposito
Journal: JAMA (2007)

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
Patient derived adenoid cystic carcinoma xenografts to examine personalized cancer treatment approaches.
Authors: Prashanth Jyothi Prabakaran, Adam D Swick, Kwang-Ok P Nickel, David T Yang, Lauryn R Werner, Justine Yang Bruce, Aaron Wieland, Timothy M McCulloch, Gregory K Hartig, Paul M. Harari, Randall J. Kimple
Journal: Journal of Clinical Oncology (2016)

e14080 Background: Adenoid cystic carcinoma (ACC) is a relatively rare cancer that typically arises in salivary tissues of the head and neck for which there are currently no approved systemic agents. The scarcity of validated model systems has hampered research efforts. Due to infrequency, large scale studies of novel therapeutics are not routinely feasible. We report the establishment and propagation of an ACC patient derived xenograft (PDX), genomic evaluation of mutations, and in vivo response profiles to personalized chemotherapy agents based on next-generation sequencing. Methods: An ACC PDX was established and maintained in NSG mice directly from the operating room. Common cancer-associated mutations were identified using the Illumina TruSeq Amplicon Cancer panel. PDXs were treated with focal radiation or chemotherapy selected based on the genomic profile of the cancer. Tumor size was measured over time. Target inhibition was confirmed in vivo via tumor lysates. Results: This ACC PDX maintains the histologic and physical characteristics of the primary human tumor. Mutations in the receptor tyrosine kinases(RTKs) cKit and KDR/VEGFR2 were identified. No mutations were identified in EGFR, RAS, or PIK3CA. Several targeted therapies were selected including dovitinib, a multi-RTK inhibitor, BEZ235, a PI3K/mTORC inhibitor, and cetuximab, an EGFR mAB. Target inhibition was confirmed by western blot of tumor lysates. Treatment with several molecular agents resulted in significant tumor growth inhibition: time to tumor doubling was 17 d in CTRL, 33 d in dovitinib, 39 d in BEZ235, and 46 d in cetuximab treated tumors. Radiation (5 Gy x 8 fractions) potently arrested tumor growth (doubling time > 70 d). Work is ongoing to identify the role of the specific cKIT and KDR mutations. Conclusions: PDXs are a valuable model system for investigating potential proof of concept for personalized approaches to cancer care. These preliminary data identify the rationale to investigate selected molecularly targeted drugs for ACC, particularly when driven by tumor specific genetic biomarkers. Expansion of these studies may be valuable to advance the design of new treatment strategies for ACC.
Contributions of Mouse and Human Hematopoietic Cells to Remodeling of the Adult Auditory Nerve After Neuron Loss
Authors: Hainan Lang, Eishi Nishimoto, Yazhi Xing, LaShardai N Brown, Kenyaria V Noble, Jeremy L Barth, Amanda C LaRue, Kiyoshi Ando, Bradley A Schulte
Journal: Molecular Therapy (2016)

The peripheral auditory nerve (AN) carries sound information from sensory hair cells to the brain. The present study investigated the contribution of mouse and human hematopoietic stem cells (HSCs) to cellular diversity in the AN following the destruction of neuron cell bodies, also known as spiral ganglion neurons (SGNs). Exposure of the adult mouse cochlea to ouabain selectively killed type I SGNs and disrupted the blood-labyrinth barrier. This procedure also resulted in the upregulation of genes associated with hematopoietic cell homing and differentiation, and provided an environment conducive to the tissue engraftment of circulating stem/progenitor cells into the AN. Experiments were performed using both a mouse-mouse bone marrow transplantation model and a severely immune-incompetent mouse model transplanted with human CD34+ cord blood cells. Quantitative immunohistochemical analysis of recipient mice demonstrated that ouabain injury promoted an increase in the number of both HSC-derived macrophages and HSC-derived nonmacrophages in the AN. Although rare, a few HSC-derived cells in the injured AN exhibited glial-like qualities. These results suggest that human hematopoietic cells participate in remodeling of the AN after neuron cell body loss and that hematopoietic cells can be an important resource for promoting AN repair/regeneration in the adult inner ear.
Effects of Increasing Screening Age and Fecal Hemoglobin Cutoff Concentrations in a Colorectal Cancer Screening Program
Authors: Els Wieten, Eline H. Schreuders, Stella A.V. Nieuwenburg, Bettina E. Hansen, Iris Lansdorp-Vogelaar, Ernst J. Kuipers, Marco J. Bruno, Manon C.W. Spaander
Journal: Clinical Gastroenterology and Hepatology (2016)
New Pharmacologic Agents That Target Inflammation and Fibrosis in Nonalcoholic Steatohepatitis–Related Kidney Disease
Authors: Giovanni Musso, Franco De Michieli, Daria Bongiovanni, Renato Parente, Luciana Framarin, Nicola Leone, Mara Berrutti, Roberto Gambino, Maurizio Cassader, Solomon Cohney, Elena Paschetta
Journal: Clinical Gastroenterology and Hepatology (2016)
Outcomes of hypofractionated palliative radiotherapy for choroidal metastases.
Authors: Ezra Hahn, Juan Pablo Velazquez-Martin, Sohel Somani, Pedro Salazar, Daniela Domville, David Payne, Wei Xu, Jie Su, Charles Pavlin, Rand Simpson, Normand Laperriere, Hatem Krema, John N. Waldron, Caroline Chung
Journal: Journal of Clinical Oncology (2015)

194 Background: External beam radiotherapy (RT) is an effective palliative treatment for choroidal metastases aimed at preserving vision and obtaining local tumor control. Delivery of 30-40 Gy in 2 Gy daily fractions is a standard approach in many centers. At our center, a shorter, more convenient schedule of 20 Gy in 5 fractions has been used in this palliative setting. This study reports the efficacy and toxicity of this hypofractionated RT approach. Methods: We conducted a retrospective review of patients treated in the Ocular Oncology clinic at Princess Margaret Cancer Center who received RT (20 Gy in 5 fractions) for choroidal metastases between January 1, 1999 and November 30, 2012. Primary outcome measures were change in visual acuity and tumor response. Secondary outcomes included toxicities of RT, tumor control, and overall survival from the date of choroidal metastases diagnosis. Results: A total of 55 patients with 71 involved eyes were included. Decreased vision was the presenting symptom in 43 eyes (61%). Visual acuity improved from a median of 20/70 to 20/40 between baseline assessment and last follow-up, and remained stable or improved in 56 eyes (80%). On ultrasound, tumor regression was observed in 64 eyes (91%) with complete response in 47 eyes (67%). Metastases progressed in 4 eyes (6%) despite RT with 1 eye requiring enucleation. Median survival after diagnosis of choroidal metastases was 13 months with estimated overall survival at 1, 2, and 3 years to be 50% (36-62), 23% (12-35), and 8% (3-18), respectively. Forty-nine patients (89%) did not experience any acute complications. Mild acute toxicities included transitory dryness in 5 patients and episcleritis in 1 patient. Cataracts developed in 4 eyes (6%), retinopathy in 1 eye, optic neuropathy in 7 eyes (10%), pigmentary maculopathy in 5 eyes (7%), and neovascular glaucoma in 1 eye. Conclusions: A short fractionation schedule of 20 Gy in 5 fractions is a well-tolerated treatment that effectively preserves vision and gains local tumor control for many patients with choroidal metastases. This hypofractionated approach would help reduce the burden of a longer treatment course in this palliative patient population.
A Genome-Wide Association Study to Identify Single-Nucleotide Polymorphisms for Acute Kidney Injury
Authors: Bixiao Zhao, Qiongshi Lu, Yuwei Cheng, Justin M. Belcher, Edward D. Siew, David E. Leaf, Simon C. Body, Amanda A. Fox, Sushrut S. Waikar, Charles D. Collard, Heather Thiessen-Philbrook, T. Alp Ikizler, Lorraine B. Ware, Charles L. Edelstein, Amit X. Garg, Murim Choi, Jennifer A. Schaub, Hongyu Zhao, Richard P. Lifton, Chirag R. Parikh
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Acute kidney injury is a common and severe complication of critical illness and cardiac surgery. Despite significant attempts at developing treatments, therapeutic advances to attenuate acute kidney injury and expedite recovery have largely failed.Identifying genetic loci associated with increased risk of acute kidney injury may reveal novel pathways for therapeutic development.We conducted an exploratory genome-wide association study to identify single-nucleotide polymorphisms associated with genetic susceptibility to in-hospital acute kidney injury.We genotyped 609,508 single-nucleotide polymorphisms and performed genotype imputation in 760 acute kidney injury cases and 669 controls. We then evaluated polymorphisms that showed the strongest association with acute kidney injury in a replication patient population containing 206 cases with 1,406 controls. We observed an association between acute kidney injury and four single-nucleotide polymorphisms at two independent loci on metaanalysis of discovery and replication populations. These include rs62341639 (metaanalysis P = 2.48 × 10-7; odds ratio [OR], 0.64; 95% confidence interval [CI], 0.55-0.76) and rs62341657 (P = 3.26 × 10-7; OR, 0.65; 95% CI, 0.55-0.76) on chromosome 4 near APOL1-regulator IRF2, and rs9617814 (metaanalysis P = 3.81 × 10-6; OR, 0.70; 95% CI, 0.60-0.81) and rs10854554 (P = 6.53 × 10-7; OR, 0.67; 95% CI, 0.57-0.79) on chromosome 22 near acute kidney injury-related gene TBX1.Our findings reveal two genetic loci that are associated with acute kidney injury. Additional studies should be conducted to functionally evaluate these loci and to identify other common genetic variants contributing to acute kidney injury.
Targeted systemic delivery of siRNA to cervical cancer model using cyclic RGD-installed unimer polyion complex-assembled gold nanoparticles
Authors: Yu Yi, Hyun Jin Kim, Peng Mi, Meng Zheng, Hiroyasu Takemoto, Kazuko Toh, Beob Soo Kim, Kotaro Hayashi, Mitsuru Naito, Yu Matsumoto, Kanjiro Miyata, Kazunori Kataoka
Journal: Journal of Controlled Release (2016)