tbuckley/cabot-search huggingface dataset:
Urinary 8-hydroxy-2'-deoxyguanosine Predicts Cardiovascular Death after Corticosteroid Therapy in Patients with Active Cardiac Sarcoidosis
Authors: Myoren Takeki, Kobayashi Shigeki, Oda Seiko, Nanno Takuma, Ishiguchi Hironori, Murakami Wakako, Okuda Shinichi, Okada Munemasa, Takemura Genzo, Yano Masafumi
Journal: Circulation (2016)
Stimulation of glioma and breast cancer cell motility by proteolysis and release of the L1 neural cell recognition molecule
Authors: Shalini Adla, Murali K. Temburni, Vivek P. Patel, Muhua Yang, Philip Kudish, Deni S. Galileo
Journal: Cancer Research (2006)

3451  Thrombosis is a frequent complication in patients with advanced gastric cancer, and previous reports have shown that gastric cancer patients, even those without thrombosis, often show abnormalities in blood coagulation data, suggesting the possibility that gastric cancer might have the potential to induce subclinical hypercoagulability. Tissue factor (TF), which normally safeguards vascular integrity by inducing hemostasis upon injury, has been shown to play roles in cancer progression and metastasis through the modulation of blood coagulation. In fact, aberrantly expressed TF in cancer cells has been reported to be associated with advanced stages of malignancy in various cancers. The expression of TF was immunohistochemically evaluated in 207 gastric cancers and their relationship with clinicopathological features was examined. Significant expression of TF was observed in 52 of 207 cases (25.1%) and associated with lymphatic and venous invasion and lymphatic metastasis as well as depth of invasion. Moreover, TF expression was associated with a worse outcome. Next, we examined the mechanism of TF to promote gastric cancer progression in NUGC-3, gastric cancer cell line, which highly expressed TF at the mRNA and protein level. We found that the addition of factor VIIa (FVIIa) induced significant levels of tyrosine phosphorylation of epidermal growth factor receptor (EGFR) in NUGC-3. Interestingly, time-course experiments revealed that phosphorylation was maximal after 20-40 minutes of stimulation and sustained at least 3 hours, which differed from the rapid EGFR transactivation caused by other G-protein coupled receptor agonists. Our results provide a novel role of the TF to modulate gastric cancer progression and suggest the possibility that sustained transactivation of EGFR is one of the mechanisms to represent the association of TF with more invasive character and worse clinical outcome in gastric cancer.
Abstract 386: The Role of GAPDH in the Cardio-metabolic Response to Ischemia
Authors: James Rhee, Nicholas Houstis, John Asara, Laura Liu, Cholsoon Jang, Zoltan Arany, Anthony Rosenzweig
Journal: Circulation Research (2015)

Fundamental changes in nutrient metabolism underlie many disease processes, including obesity, diabetes, and cancer. Metabolic derangements are also a hallmark of heart disease, both in the context of failure and ischemia, and likely contributors to its etiology. For example, while the healthy heart favors fats as a fuel, failing hearts will consume more glucose; but it is unclear if this is pathological or protective. It is very likely that manipulation of metabolic pathways can affect, and possibly augment and protect, heart function. Yet no drug therapy exists that targets cardiac metabolism. Staples of ischemic disease management largely focus on anti-platelet, cholesterol-lowering, and beta-adrenergic blocking regimens. Heart failure medicines focus on maladaptive neuro-hormonal responses, a strategy several decades old. Our goal here is to delineate exactly how critical aspects of metabolism are altered in cardiac ischemia, and to identify new targets of pharmacological intervention. Metabolism largely remains unexplored because of its intricate network of regulation, compounded by the fact that variations in this network will often escape traditional methods of gene expression profiling. But by using high throughput metabolomic and proteomic platforms, we have striking evidence that the glycolytic enzyme glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is instrumental in the heart’s response to ischemia. Dynamic, real-time metabolomic flux using heavy carbon isotope labeling points toward a partial shift of glycolytic intermediates toward lipid synthesis during ischemic stress in cardiomyocytes, precisely at the step catalyzed by GAPDH. Expansive phospho-proteomic analyses from Langendorff ex vivo hanging heart experiments show that this shift in metabolism may be triggered by an inhibitory phosphorylation of GAPDH. Our hypothesis that glycolysis is in part rerouted toward triglyceride synthesis is a revolutionary departure from decades-old perceptions of energy management. Modulating GAPDH function, either directly or indirectly via partner proteins, may offer insight into untapped areas of therapy. Our early attempts with chemicals that inhibit GAPDH already show heart cells with improved survival under ischemia.
Cost-effectiveness of Evolocumab Therapy for Reducing Cardiovascular Events in Patients With Atherosclerotic Cardiovascular Disease
Authors: Gregg C. Fonarow, Anthony C. Keech, Terje R. Pedersen, Robert P. Giugliano, Peter S. Sever, Peter Lindgren, Ben van Hout, Guillermo Villa, Yi Qian, Ransi Somaratne, Marc S. Sabatine
Journal: JAMA Cardiology (2017)

The proprotein convertase subtilisin/kexin type 9 inhibitor evolocumab has been demonstrated to reduce the composite of myocardial infarction, stroke, or cardiovascular death in patients with established atherosclerotic cardiovascular disease. To our knowledge, long-term cost-effectiveness of this therapy has not been evaluated using clinical trial efficacy data.To evaluate the cost-effectiveness of evolocumab in patients with atherosclerotic cardiovascular disease when added to standard background therapy.A Markov cohort state-transition model was used, integrating US population-specific demographics, risk factors, background therapy, and event rates along with trial-based event risk reduction. Costs, including price of drug, utilities, and transitional probabilities, were included from published sources.Addition of evolocumab to standard background therapy including statins.Cardiovascular events including myocardial infarction, ischemic stroke and cardiovascular death, quality-adjusted life-year (QALY), incremental cost-effectiveness ratio (ICER), and net value-based price.In the base case, using US clinical practice patients with atherosclerotic cardiovascular disease with low-density lipoprotein cholesterol levels of at least 70 mg/dL (to convert to millimoles per liter, multiply by 0.0259) and an annual events rate of 6.4 per 100 patient-years, evolocumab was associated with increased cost and improved QALY: incremental cost, $105 398; incremental QALY, 0.39, with an ICER of $268 637 per QALY gained ($165 689 with discounted price of $10 311 based on mean rebate of 29% for branded pharmaceuticals). Sensitivity and scenario analyses demonstrated ICERs ranging from $100 193 to $488 642 per QALY, with ICER of $413 579 per QALY for trial patient characteristics and event rate of 4.2 per 100 patient-years ($270 192 with discounted price of $10 311) and $483 800 if no cardiovascular mortality reduction emerges. Evolocumab treatment exceeded $150 000 per QALY in most scenarios but would meet this threshold at an annual net price of $9669 ($6780 for the trial participants) or with the discounted net price of $10 311 in patients with low-density lipoprotein cholesterol levels of at least 80 mg/dL.At its current list price of $14 523, the addition of evolocumab to standard background therapy in patients with atherosclerotic cardiovascular disease exceeds generally accepted cost-effectiveness thresholds. To achieve an ICER of $150 000 per QALY, the annual net price would need to be substantially lower ($9669 for US clinical practice and $6780 for trial participants), or a higher-risk population would need to be treated.
A mutational signature reveals alterations underlying deficient homologous recombination repair in breast cancer
Authors: Paz Polak, Jaegil Kim, Lior Z Braunstein, Rosa Karlic, Nicholas J Haradhavala, Grace Tiao, Daniel Rosebrock, Dimitri Livitz, Kirsten Kübler, Kent W Mouw, Atanas Kamburov, Yosef E Maruvka, Ignaty Leshchiner, Eric S Lander, Todd R Golub, Aviad Zick, Alexandre Orthwein, Michael S Lawrence, Rajbir N Batra, Carlos Caldas, Daniel A Haber, Peter W Laird, Hui Shen, Leif W Ellisen, Alan D D'Andrea, Stephen J Chanock, William D Foulkes, Gad Getz
Journal: Nature Genetics (2017)
吸収性透過性ナノ粒子を用いた注射可能な無細胞マトリックス足場は神経膠芽腫に対するドセタキセルの治療効果を改善する【Powered by NICT】
Authors: Xu He-Lin, Mao Kai-Li, Lu Cui-Tao, Fan Zi-Liang, Yang Jing-Jing, Xu Jie, Chen Pian-Pian, ZhuGe De-Li, Shen Bi-Xin, Jin Bing-Hui, Xiao Jian, Zhao Ying-Zheng
Journal: Biomaterials (2016)
Statistics Notes: Percentage differences, symmetry, and natural logarithms
Authors: Tim J Cole, Douglas G Altman
Journal: BMJ (2017)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following Statistics Notes: Percentage differences, symmetry, and natural logarithms Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Predictions for short- and long-term survival after ICU admission in advanced cancer patients.
Authors: Su Jin Heo, Joo Hyuk Sohn, Kyung Soo Chung, Soohyeon Lee
Journal: Journal of Clinical Oncology (2014)

e20534 Background: Intensive care unit (ICU) admission in advanced cancer patients remains debated because of the poor short-term prognosis. However, ICU admission of these patients should also be assessed on the possibility to administer specific anticancer treatment, tumor characteristics and the long-term outcome therefore. Methods: We analyzed in 116 advanced cancer patients admitted to the ICU at Severance hospital, Yonsei university between Jan 2010 and Dec 2012. We excluded palliative care only patients. We analyzed demographic, clinical and survival data of patients admitted at ICU and identify prognostic and predictive factors presented at ICU admission that could be compared with short- and long-term survival. Results: Of the 116 patients, the median age at ICU admission was 64 years (59.5% males, 40.5% females). Lung, breast, and stomach were common sites of the primary tumors, 87(75%) patients underwent active anticancer treatment in recent 30 days. As the main cause of ICU admission was acute respiratory failure (73%), 102(87.9%) patients were managed in conventional mechanical ventilation, 99(85.3%) patients in vasopressor and 31(26.7%) patients in continuous renal replacement therapy (CRRT). 24 (20.7%) patients were post resuscitation status before ICU admission. The ICU, hospital and 6-month survival rates were 51.7%, 31.0%, and 15.5%, respectively. APACHE II score (HR: 2.86, 95% CI: 1.00-8.15, P <0.050) and the need for CRRT (HR:2.14, 95% CI 1.24-3.70, P <0.007) were associated with ICU mortality by Cox-regression analysis. However, Eastern Cooperative Oncology Group (ECOG) performance status (HR 1.64, 95% CI 1.03-2.62, P <0.010) is associated poor prognosis and controlled disease status (HR 0.372, 95% CI 0.21-0.67, P <0.001) is good prognostic factor for 6-month survival after ICU admission. Conclusions: To determine short term survival, clinical factors presenting acute illness at ICU admission, such as APACHE II score, the need of CRRT, were higher associated ICU mortality than factors related to the malignancy itself. However, we have to assess the comprehensive approach considering cancer biology, disease control status in terms of long term survival.
Kinetics of Zika Viral Load in Semen
Authors: Franck de Laval, Séverine Matheus, Thomas Labrousse, Antoine Enfissi, Dominique Rousset, Sébastien Briolant
Journal: New England Journal of Medicine (2017)

A study conducted in French Guiana showed that not all men who are symptomatically infected with Zika virus have ZIKV RNA detectable in semen. In addition, the average duration of detection in semen was shorter than has been reported previously.
Sequential, Multiple Assignment, Randomized Trial Designs in Immuno-oncology Research
Authors: Kelley M. Kidwell, Michael A. Postow, Katherine S. Panageas
Journal: Clinical Cancer Research (2017)

Clinical trials investigating immune checkpoint inhibitors have led to the approval of anti-CTLA-4 (cytotoxic T-lymphocyte antigen-4), anti-PD-1 (programmed death-1), and anti-PD-L1 (PD-ligand 1) drugs by the FDA for numerous tumor types. In the treatment of metastatic melanoma, combinations of checkpoint inhibitors are more effective than single-agent inhibitors, but combination immunotherapy is associated with increased frequency and severity of toxicity. There are questions about the use of combination immunotherapy or single-agent anti-PD-1 as initial therapy and the number of doses of either approach required to sustain a response. In this article, we describe a novel use of sequential, multiple assignment, randomized trial (SMART) design to evaluate immune checkpoint inhibitors to find treatment regimens that adapt within an individual based on intermediate response and lead to the longest overall survival. We provide a hypothetical example SMART design for BRAF wild-type metastatic melanoma as a framework for investigating immunotherapy treatment regimens. We compare implementing a SMART design to implementing multiple traditional randomized clinical trials. We illustrate the benefits of a SMART over traditional trial designs and acknowledge the complexity of a SMART. SMART designs may be an optimal way to find treatment strategies that yield durable response, longer survival, and lower toxicity. Clin Cancer Res; 24(4); 730-6. ©2017 AACR.
The Trump Administration and the Abandonment of Teen Pregnancy Prevention Programs
Authors: R. Alta Charo
Journal: JAMA Internal Medicine (2017)

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 Internal Medicine 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 Internal Medicine journal
Ruxolitinib for essential thrombocythemia refractory to or intolerant of hydroxyurea: long-term phase 2 study results
Authors: Srdan Verstovsek, Francesco Passamonti, Alessandro Rambaldi, Giovanni Barosi, Elisa Rumi, Elisabetta Gattoni, Lisa Pieri, Huiling Zhen, Muriel Granier, Albert Assad, Mario Cazzola, Hagop M. Kantarjian, Tiziano Barbui, Alessandro M. Vannucchi
Journal: Blood (2017)
Impact of Therapy on Genomics and Transcriptomics in High-Risk Prostate Cancer Treated with Neoadjuvant Docetaxel and Androgen Deprivation Therapy
Authors: Himisha Beltran, Alexander W. Wyatt, Edmund C. Chedgy, Adam Donoghue, Matti Annala, Evan W. Warner, Kevin Beja, Michael Sigouros, Fan Mo, Ladan Fazli, Colin C. Collins, James Eastham, Michael Morris, Mary-Ellen Taplin, Andrea Sboner, Susan Halabi, Martin E. Gleave
Journal: Clinical Cancer Research (2017)

Abstract Purpose: The combination of docetaxel chemotherapy and androgen deprivation therapy (ADT) has become a standard treatment for patients with metastatic prostate cancer. The recently accrued phase III CALGB 90203 trial was designed to investigate the clinical effectiveness of this treatment approach earlier in the disease. Specimens from this trial offer a unique opportunity to interrogate the acute molecular response to docetaxel and ADT and identify potential biomarkers. Experimental Design: We evaluated baseline clinical data, needle biopsies, and radical prostatectomy (RP) specimens from 52 (of 788) patients enrolled on CALGB 90203 at one high volume center. Pathology review, tumor and germline-targeted DNA sequencing (n = 72 genes), and expression profiling using NanoString platform (n = 163 genes) were performed to explore changes in critical prostate cancer pathways linked to aggression and resistance. Results: Three of 52 patients had only microfocal residual cancer at prostatectomy. The most common alterations included TMPRSS2-ERG fusion (n = 32), TP53 mutation or deletion (n = 11), PTEN deletion (n = 6), FOXA1 (n = 6), and SPOP (n = 4) mutation, with no significant enrichment in posttreated specimens. We did not observe AR amplification or mutations. The degree of AR signaling suppression varied among treated tumors and there was upregulation of both AR and AR-V7 expression as well as a subset of neuroendocrine and plasticity genes. Conclusions: These data support the feasibility of targeted and temporal genomic and transcriptome profiling of neoadjuvant-treated prostate cancer with limited formalin-fixed paraffin embedded tissue requirement. Characterization of the heterogeneity of treatment response and molecular outliers that arise posttreatment provides new insight into potential early markers of resistance. Clin Cancer Res; 23(22); 6802–11. ©2017 AACR.
LONGITUDINAL CHANGES IN RENAL FUNCTION IN LIVER TRANSPLANT RECIPIENTS: IMPACT OF ACUTE KIDNEY INJURY AND THE ASSESSMENT OF THE DECLINE IN GLOMERULAR FILTRATION RATE OVER 5 YEARS POST LIVER TRANSPLANTATION
Authors: Andrew J. Slack, Mark McPhail, Rachel H. Westbrook, Nigel Heaton, Michael Heneghan, John G. O'Grady, Georg Auzinger, William Bernal, Christopher Willars, Kosh Agarwal, Varuna Aluvihare, Abid Suddle, Julia Wendon
Journal: Hepatology (2010)
抗カルバミル化タンパク質(anti-CarP)抗体は関節リウマチの発症に先行する
Authors: Shi Jing, Van De Stadt Lotte A, Levarht E W Nivine, Huizinga Tom W J, Hamann Doerte, Van Schaardenburg Dirkjan, Toes Rene E M, Trouw Leendert A
Journal: Annals of the Rheumatic Diseases (2014)
Randomized phase III trial of paclitaxel/carboplatin (PC) versus cisplatin/irinotecan (CPT-P) as first-line chemotherapy in patients with clear cell carcinoma (CCC) of the ovary: A Japanese Gynecologic Oncology Group (JGOG)/GCIG study.
Authors: Aikou Okamoto, Toru Sugiyama, Tetsutaro Hamano, Jae Weon Kim, Byoung Gie Kim, Takayuki Enomoto, Daisuke Aoki, Yasuhisa Terao, Nao Suzuki, Mikio Mikami, Nobuo Yaegashi, Kiyoko Kato, Hiroyuki Yoshikawa, Sandro Pignata, Jerome Alexandre, John A. Green, Seiji Isonishi, Fumitoshi Terauchi, Keiichi Fujiwara, Kazunori Ochiai
Journal: Journal of Clinical Oncology (2014)

5507 Background: CCC is a histologic subtype of epithelial ovarian cancer showing different clinical and biological characteristics. CCC has become well known for its resistance to current standard chemotherapy (PC). Our previous trial demonstrated the potential benefit of CPT-P regimen on CCC. Methods: Patients (pts) with Stage I-IV CCC were randomized to receive paclitaxel 175mg/m2 plus carboplatin AUC6 IV q3wk or irinotecan 60mg/m2 IV (days 1, 8, 15) plus cisplatin 60mg/m2 IV (day 1) q4wk for 6 cycles. International central pathologic review was performed for all cases. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), response rate per RECIST, and adverse events. Adverse events were graded according to NCI-CTCAE, version 3.0. Results: From November 2006 to March 2011, 667 patients were registered, and 619 pts were clinically and pathologically eligible for evaluation (305 pts in PC arm and 314 pts in CPT-P arm). Median age was 53 years. Baseline pt characteristics were not significantly different. Following 44.3 months median follow-up, 2-years PFS was 73.0% (95% CI:67.7-77.5) in the CPT-P arm vs. 77.6% (95% CI:72.4-81.9) in the PC arm, which was not significantly different (HR:1.171, 95% CI:0.867-1.581, p=0.303). Two-years OS was 85.5% in CPT-P arm (95% CI:81.1-89.0) and 87.4% in PC arm (95% CI:83.1-90.7), respectively (HR:1.133, 95% CI:0.796-1.613, p=0.486). Grade 3/4 leukopenia, neutropenia, thrombocytopenia, peripheral sensory neuropathy and joint pain occurred more frequently in the PC arm, whilst grade 3/4 anorexia, diarrhea, nausea, vomiting and febrile neutropenia occurred more frequently in the CPT-P arm. Conclusions: In this first CCC-specific international clinical trial, survival benefit was not observed by CPT-P. Since both regimens were well tolerated and the toxicity profiles were different, CPT-P can be an alternative regimen for CCC.
Molecular cloning and functional identification of sterol C24-methyltransferase gene from Tripterygium wilfordii
Authors: Hongyu Guan, Yujun Zhao, Ping Su, Yuru Tong, Yujia Liu, Tianyuan Hu, Yifeng Zhang, Xianan Zhang, Jia Li, Xiaoyi Wu, Luqi Huang, Wei Gao
Journal: Acta Pharmaceutica Sinica B (2017)

Sterol C24-methyltransferase (SMT) plays multiple important roles in plant growth and development. SMT1, which belongs to the family of transferases and transforms cycloartenol into 24-methylene cycloartenol, is involved in the biosynthesis of 24-methyl sterols. Here, we report the cloning and characterization of a cDNA encoding a sterol C24-methyltransferase from Tripterygium wilfordii (TwSMT1). TwSMT1 (GenBank access number KU885950) is a 1530 bp cDNA with a 1041 bp open reading frame predicted to encode a 346-amino acid, 38.62 kDa protein. The polypeptide encoded by the SMT1 cDNA was expressed and purified as a recombinant protein from Escherichia coli (E. coli) and showed SMT activity. The expression of TwSMT1 was highly up-regulated in T. wilfordii cell suspension cultures treated with methyl jasmonate (MeJA). Tissue expression pattern analysis showed higher expression in the phellem layer compared to the other four organs (leaf, stem, xylem and phloem), which is about ten times that of the lowest expression in leaf. The results are meaningful for the study of sterol biosynthesis of T. wilfordii and will further lay the foundations for the research in regulating both the content of other main compounds and growth and development of T. wilfordii.