tbuckley/cabot-search huggingface dataset:
Clinical implementation of a comprehensive targeted amplicon sequencing system for cancer in Japan.
Authors: Hideyuki Hayashi, Shigeki Tanishima, Ryo Mori, Yasunobu Okamura, Toraji Amano, Ichiro Kinoshita, Yoshito Komatsu, Hirotoshi Akita, Hiroshi Nishihara
Journal: Journal of Clinical Oncology (2017)

e13115 Background: The development of clinical sequence systems in hospitals is a critical issue in Japan, especially for medical oncology, as multiplex gene profiling enables precision medicine for cancer. We have launched an in-house clinical sequencing system,“CLHURC” to perform exhaustive targeted exome sequencing for patients with all types of cancer, as an outpatient service. We have analyzed the clinical utility of this system. Methods: Genomic DNA was extracted from tumor tissues and peripheral blood sera of 81 patients with different stages of cancer, during April-December 2016. The top five types of primary cancer were pancreas (16%), colorectal (16%), breast (10%), stomach (9%), and lung (6%). We performed a targeted amplicon exome sequencing for 160 cancer-related genes. The sequencing data was analyzed using an original bioinformatics pipeline within three days, and we identified cancer-specific somatic gene alterations such as SNV (Single Nucleotide Variation), Ins (Insertion)/Del (Deletion), and CNV (Copy Number Variation). The primary endpoints were the detection rates of potential actionable and druggable genes. The secondary endpoints were the detection rates of incidental germline variants and the period from initial visit to elucidation of the results to the patients. Results: Actionable and druggable gene alterations were detected in 90% (73/81) and 51% (41/81) of the subjects, respectively. Druggable gene alterations were frequently detected in BRCA1/2 (11/41), PIK3CA (9/41), AKT1/2 (6/41), TSC1 (5/41), and PTEN (5/41). Surprisingly, incidental germline variants were detected in 31% (25/81) of the patients, and were found in BRCA1/2 (5/25), APC (5/25), and TSC1(3/25), among others. The median period of examination was 21 days (10-66 days). Twelve out of the 81 patients (15%) were treated with therapeutic agents, based on the results of our clinical sequencing. Conclusions: We have established a robust in-house clinical sequencing system, “CLHURC,” and have initiated the development of precision medicine for cancer in Japan. Our novel clinical sequencing system could improve individualized medicine against cancer throughout Japan and Asia.
Inflammatory Monocytes Promote Perineural Invasion via CCL2-Mediated Recruitment and Cathepsin B Expression
Authors: Richard L. Bakst, Huizhong Xiong, Chun-Hao Chen, Sylvie Deborde, Anna Lyubchik, Yi Zhou, Shizhi He, William McNamara, Sei-Young Lee, Oakley C. Olson, Ingrid M. Leiner, Andrea R. Marcadis, James W. Keith, Hikmat A. Al-Ahmadie, Nora Katabi, Ziv Gil, Efsevia Vakiani, Johanna A. Joyce, Eric Pamer, Richard J. Wong
Journal: Cancer Research (2017)

Abstract Perineural invasion (PNI) is an ominous event strongly linked to poor clinical outcome. Cells residing within peripheral nerves collaborate with cancer cells to enable PNI, but the contributing conditions within the tumor microenvironment are not well understood. Here, we show that CCR2-expressing inflammatory monocytes (IM) are preferentially recruited to sites of PNI, where they differentiate into macrophages and potentiate nerve invasion through a cathepsin B–mediated process. A series of adoptive transfer experiments with genetically engineered donors and recipients demonstrated that IM recruitment to nerves was driven by CCL2 released from Schwann cells at the site of PNI, but not CCL7, an alternate ligand for CCR2. Interruption of either CCL2–CCR2 signaling or cathepsin B function significantly impaired PNI in vivo. Correlative studies in human specimens demonstrated that cathepsin B–producing macrophages were enriched in invaded nerves, which was associated with increased local tumor recurrence. These findings deepen our understanding of PNI pathogenesis and illuminate how PNI is driven in part by corruption of a nerve repair program. Further, they support the exploration of inhibiting IM recruitment and function as a targeted therapy for PNI. Cancer Res; 77(22); 6400–14. ©2017 AACR.
Further approaches to reduce the cost of renal replacement therapy
Authors: Raymond Vanholder, Lieven Annemans, Edwina Brown, Ron Gansevoort, Judith J. Gout-Zwart, Norbert Lameire, Rachael L. Morton, Rainer Oberbauer, Maarten J. Postma, Marcello Tonelli, Wim Van Biesen, Carmine Zoccali
Journal: Nature Reviews Nephrology (2017)
Urine Drug Screens to Monitor Opioid Use for Managing Chronic Pain
Authors: Shannon Haymond, Geeta Nagpal, Heather Heiman
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Prognostic significance of the neutrophil-lymphocyte ratio (NLR) in phase 1 clinical trial patients.
Authors: Rajiv Kumar, Elena Geuna, Vasiliki Michalarea, Ulrike Naumann, Johann Sebastian De Bono
Journal: Journal of Clinical Oncology (2014)

3037 Background: Inflammation has a critical role in the pathogenesis and progression of tumours. A high pre-treatment NLR has been associated with a poor prognosis. Its prognostic utility in patients (pts) being treated on Phase I trials remains uncertain. Methods: We identified 300 pts treated on Phase 1 clinical trials at the RMH, between January 2007 and November 2013. Data was collected on pt, treatment and tumour characteristics, including baseline RMH score, neutrophil count and lymphocyte count. Results: Overall, 47% of the pts were male; 35% had ECOG 0 and 64% ECOG 1. Tumour types included 15% breast, 13% colorectal, 13% ovarian, 13% non-small cell lung, 14% prostate and 32% other. The RMH score was 0 in 23%, 1 in 43%, 2 in 31% and 3 in 3%. The median NLR was 3.08 (IQR 2.06 – 4.49). Median overall survival (OS) for the NLR quartiles was 10.5 mths for quartile 1, 10.3 mths for quartile 2, 7.9 mths for quartile 3 and 6.5 mths for quartile 4 (P<0.0001 for trend). In a univariate model for OS, median OS for a low vs high RMH score was 10.6 vs 5.8 mths (HR 0.55, P<0.0001). In addition, ECOG (0 vs 1-2) was significant (HR 0.62, P=0.002), as was the NLR when assessed for the binary thresholds defined by the quartiles (NLR25: HR 0.79, P = 0.04; NLR 50: HR 0.57, P = 0.0001; NLR 75: HR 0.50, P= 0.0001). Age, gender and steroid use, were not significant. In a multivariate model for OS, the RMH score and ECOG remained significant (HR 0.63, P=0.002 and HR 0.71, P 0.03, respectively). When the NLR measures were added, NLR (continuous variable) remained a significant prognostic factor (HR 1.06, P <0.0001) as did Log10NLR (HR 2.61, P=0.001. The interaction test between the RMH score and the NLR measures was negative. ROC curve analysis showed that the RMH score had a C-index of 0.630, P = 0.0002. The models assessed included: RMH + NLR, RMH + Log10NLR, RMH x NLR, and RMH x Log10NLR. However, pairwise comparisons of the C-indices from these models to the RMH score alone showed no significant improvement in C-index. Conclusions: NLR is prognostic for OS in a Phase I population, independent of the RMH score, in a multivariate analysis.
Bleak outlook for community substance misuse services
Authors: Joss Bray
Journal: BMJ (2017)

The UK government’s drug strategy for 2017 effectively announces the end of community substance misuse services.1 The grant from Public Health England to local authorities to commission these services is labelled as being “ring fenced.” But when local authorities are not legally required to provide services, ring fencing seems to disappear, and funding cuts of a …
Inhibition of 5-lipoxygenase alleviates graft-versus-host disease
Authors: Barbara Maximino Rezende, Rayssa Maciel Athayde, William Antônio Gonçalves, Carolina Braga Resende, Priscila Teles de Tolêdo Bernardes, Denise Alves Perez, Lísia Esper, Alesandra Côrte Reis, Milene Alvarenga Rachid, Marina Gomes Miranda e Castor, Thiago Mattar Cunha, Fabiana Simão Machado, Mauro Martins Teixeira, Vanessa Pinho
Journal: The Journal of Experimental Medicine (2017)

Leukotriene B4 (LTB4), a proinflammatory mediator produced by the enzyme 5-lipoxygenase (5-LO), is associated with the development of many inflammatory diseases. In this study, we evaluated the participation of the 5-LO/LTB4 axis in graft-versus-host disease (GVHD) pathogenesis by transplanting 5-LO-deficient leukocytes and investigated the effect of pharmacologic 5-LO inhibition by zileuton and LTB4 inhibition by CP-105,696. Mice that received allogeneic transplant showed an increase in nuclear 5-LO expression in splenocytes, indicating enzyme activation after GVHD. Mice receiving 5-LO-deficient cell transplant or zileuton treatment had prolonged survival, reduced GVHD clinical scores, reduced intestinal and liver injury, and decreased levels of serum and hepatic LTB4 These results were associated with inhibition of leukocyte recruitment and decreased production of cytokines and chemokines. Treatment with CP-105,696 achieved similar effects. The chimerism or the beneficial graft-versus-leukemia response remained unaffected. Our data provide evidence that the 5-LO/LTB4 axis orchestrates GVHD development and suggest it could be a target for the development of novel therapeutic strategies for GVHD treatment.
Comparative efficacy and safety of bone-modifying agents for the treatment of bone metastases in patients with advanced renal cell carcinoma: A systematic review and meta-analysis.
Authors: Kenji Omae, Yasushi Tsujimoto, Michitaka Honda, Tsunenori Kondo, Yasunobu Hashimoto, Kazunari Tanabe, Shunichi Fukuhara, Toshi Furukawa
Journal: Journal of Clinical Oncology (2017)

e16067 Background: Bone-modifying agents (BMA) have been well-demonstrated to be effective for preventing and inhibiting skeletal-related events (SRE) in patients with bone metastases of breast or prostate cancer. However, the role of BMA treatment has not yet been clearly defined in patients with bone metastases of renal cell carcinoma (RCC). We, therefore, conducted a systematic review and meta-analysis to evaluate the efficacy and safety of BMA in patients with bone metastases of RCC. Methods: Literature search was conducted on MEDLINE, the Cochrane Central Register of Controlled Trials, the WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov to identify randomized controlled trials of BMA for the treatment of bone metastases in RCC patients. The primary outcomes were SRE and serious adverse events (AEs). Hazard ratios (HRs) were calculated with a random effects model. The Grading of Recommendation Assessment, Development, and Evaluation (GRADE) approach was used to assess the certainty of the evidence. This review was prospectively registered on PROSPERO (No. CRD42016032742). Results: Three studies (259 patients) were identified for the systematic review. Two studies that compared zoledronic acid with placebo or non-zoledronic acid showed that zoledronic acid reduced the SRE risk by 68% (HR 0.32; 95% confidence interval (CI) 0.19–0.55; P &lt; 0.0001). The quality of evidence was moderate. No serious osteonecrosis was reported in both studies. The incidence of serious AEs was identical (80%) on both treatment arms in one study and not reported in the other study. In the remaining study, which compared denosumab with zoledronic acid, analyses of the individual patient data shared through Amgen showed a favorable trend for denosumab in terms of SRE (HR 0.71; 95% CI 0.43–1.17) and serious AEs (risk ratio 0.86; 95% CI 0.68–1.08), but this trend did not reach statistical significance. Conclusions: The moderate-quality evidence indicates that zoledronic acid significantly reduces the risk of SRE among patients with bone metastases of RCC.
Does Cardiorespiratory Fitness Attenuate the Adverse Effects of Severe/Morbid Obesity on Cardiometabolic Risk and Insulin Resistance in Children? A Pooled Analysis
Authors: Christine Delisle Nyström, Pontus Henriksson, Vicente Martínez-Vizcaíno, María Medrano, Cristina Cadenas-Sanchez, Natalia María Arias-Palencia, Marie Löf, Jonatan R. Ruiz, Idoia Labayen, Mairena Sánchez-López, Francisco B. Ortega
Journal: Diabetes Care (2017)

To investigate 1) differences in cardiometabolic risk and HOMA of insulin resistance (HOMA-IR) across BMI categories (underweight to morbid obesity), 2) whether fit children have lower cardiometabolic risk/HOMA-IR than unfit children in each BMI category, and 3) differences in cardiometabolic risk/HOMA-IR in normal-weight unfit children and obese fit children.A pooled study including cross-sectional data from three projects (n = 1,247 children aged 8-11 years). Cardiometabolic risk was assessed using the sum of the sex- and age-specific z scores for triglycerides, HDL cholesterol, glucose, and the average of systolic and diastolic blood pressure and HOMA-IR.A significant linear association was observed between the risk score and BMI categories (P trend ≤0.001), with every incremental rise in BMI category being associated with a 0.5 SD higher risk score (standardized β = 0.474, P < 0.001). A trend was found showing that as BMI categories rose, cardiorespiratory fitness (CRF) attenuated the risk score, with the biggest differences observed in the most obese children (-0.8 SD); however, this attenuation was significant only in mild obesity (-0.2 SD, P = 0.048). Normal-weight unfit children had a significantly lower risk score than obese fit children (P < 0.001); however, a significant reduction in the risk score was found in obese fit compared with unfit children (-0.4 SD, P = 0.027). Similar results were obtained for HOMA-IR.As BMI categories rose so did cardiometabolic risk and HOMA-IR, which highlights the need for obesity prevention/treatment programs in childhood. Furthermore, CRF may play an important role in lowering the risk of cardiometabolic diseases in obese children.
Abstract 15078: Long-Non-Coding RNA HypERrlnc Regulates Human Pericyte Function by Modulation of the Endoplasmic Reticulum-Stress Cell Response
Authors: Florian Bischoff, Astrid Werner, Jes-Niels Boeckel, Shemsi Demolli, Katharina Michalik, Benjamin Meder, Hugo A Katus, Jan Haas, Wei Chen, David John, Shizuka Uchida, Andreas M Zeiher, Stefanie Dimmeler, Christoph M Zehendner
Journal: Circulation (2016)

Introduction:  Pericytes are perivascular mural cells that induce vessel maturation and endothelial barrier function. Long non-coding RNAs (lncRNAs) are known to influence endothelial cell function, but their role in pericyte biology remains unexplored. Endoplasmic reticulum (ER) stress is a common cellular response upon stimuli such as hypoxia that triggers cell death and consecutive organ dysfunction. Here we show that lncRNA HypeERlnc (Hypoxia-Induced Endoplasmic Reticulum-Stress Regulating RNA) affects pericyte function by modulating the ER-stress cell response.   Methods and Results:  RNA seq identified 30 hypoxia regulated lncRNAs in primary human pericytes (hPC), including HypERrlnc. Silencing HypERrlnc, which is enriched in the nucleus (nucleus/cytosol ratio: 1.55±0.09, n=3), with LNA-GapmeRs decreased cell viability (MTT assay: 0.77±0.02 vs Ctrl, P   Conclusion:  LncRNA HypERrlnc regulates the evolution of ER-stress and is important for pericyte survival, proliferation, differentiation, coronary endothelial recruitment and endothelial barrier function. Moreover, downregulation of HypERrlnc in chronic heart failure indicates a role of HypERrlnc in human cardiac disease.
Degalactotigonin, a Natural Compound from <i>Solanum nigrum L</i>., Inhibits Growth and Metastasis of Osteosarcoma through GSK3β Inactivation–Mediated Repression of the Hedgehog/Gli1 Pathway
Authors: Zhiqiang Zhao, Qiang Jia, Man-Si Wu, Xianbiao Xie, Yongqian Wang, Guohui Song, Chang-Ye Zou, Qinglian Tang, Jinchang Lu, Gang Huang, Jin Wang, De-Chen Lin, H. Phillip Koeffler, Jun-Qiang Yin, Jingnan Shen
Journal: Clinical Cancer Research (2017)

Abstract Purpose: Agents extracted from natural sources with antitumor property have attracted considerable attention from researchers and clinicians because of their safety, efficacy, and immediate availability. Degalactotigonin (DGT), extracted from Solanum nigrum L., has anticancer properties without serious side effects. Here, we explored whether DGT can inhibit the growth and metastasis of osteosarcoma. Experimental Design: MTT, colony formation, and apoptosis assays were performed to analyze the effects of DGT on osteosarcoma cell viability in vitro. The migration and invasion abilities were measured using a Transwell assay. Animal models were used to assess the roles of DGT in both tumor growth and metastasis of osteosarcoma. Gli1 expression and function were measured in osteosarcoma cells and clinical samples. After DGT treatment, Gli1 activation and the phosphorylation status of multiple cellular kinases were measured with a luciferase reporter and phospho-kinase antibody array. Results: DGT inhibited proliferation, induced apoptosis, and suppressed migration and invasion in osteosarcoma cells. DGT, injected intraperitoneally after tumor inoculation, significantly decreased the volume of osteosarcoma xenografts and dramatically diminished the occurrence of osteosarcoma xenograft metastasis to the lungs. Mechanistically, DGT inhibited osteosarcoma growth and metastasis through repression of the Hedgehog/Gli1 pathway, which maintains malignant phenotypes and is involved in the prognosis of osteosarcoma patients. DGT decreased the activity of multiple intracellular kinases that affect the survival of osteosarcoma patients, including GSK3β. In addition, DGT represses the Hedgehog/Gli1 pathway mainly through GSK3β inactivation. Conclusions: Our studies provide evidence that DGT can suppress the growth and metastasis of human osteosarcoma through modulation of GSK3β inactivation–mediated repression of the Hedgehog/Gli1 pathway. Clin Cancer Res; 24(1); 130–44. ©2017 AACR.
The Influence of Hyaluronic Acid and Glioblastoma Cell Coculture on the Formation of Endothelial Cell Networks in Gelatin Hydrogels
Authors: Mai T. Ngo, Brendan A. Harley
Journal: Advanced Healthcare Materials (2017)

Abstract Glioblastoma (GBM) is the most common and deadly form of brain cancer. Interactions between GBM cells and vasculature in vivo contribute to poor clinical outcomes, with GBM‐induced vessel co‐option, regression, and subsequent angiogenesis strongly influencing GBM invasion. Here, elements of the GBM perivascular niche are incorporated into a methacrylamide‐functionalized gelatin hydrogel as a means to examine GBM–vessel interactions. The complexity of 3D endothelial cell networks formed from human umbilical vein endothelial cells and normal human lung fibroblasts as a function of hydrogel properties and vascular endothelial growth factor (VEGF) presentation is presented. While overall length and branching of the endothelial cell networks decrease with increasing hydrogel stiffness and incorporation of brain‐mimetic hyaluronic acid, it can be separately altered by changing the vascular cell seeding density. It is shown that covalent incorporation of VEGF supports network formation as robustly as continuously available soluble VEGF. The impact of U87‐MG GBM cells on the endothelial cell networks is subsequently investigated. GBM cells localize in proximity to the endothelial cell networks and hasten network regression in vitro. Together, this in vitro platform recapitulates the close association between GBM cells and vessel structures as well as elements of vessel co‐option and regression preceding angiogenesis in vivo.
Guns and Violent Media—A Toxic Mix With an Available Antidote
Authors: Dimitri A. Christakis, Frederick P. Rivara
Journal: JAMA Pediatrics (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 Pediatrics 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 Pediatrics journal
Confirmed efficacy of etoposide and dexamethasone in HLH treatment: long-term results of the cooperative HLH-2004 study
Authors: Elisabet Bergsten, AnnaCarin Horne, Maurizio Aricó, Itziar Astigarraga, R. Maarten Egeler, Alexandra H. Filipovich, Eiichi Ishii, Gritta Janka, Stephan Ladisch, Kai Lehmberg, Kenneth L. McClain, Milen Minkov, Scott Montgomery, Vasanta Nanduri, Diego Rosso, Jan-Inge Henter
Journal: Blood (2017)
The Safety and Efficacy of Full Versus Reduced Dose Betrixaban in the Acute Medically Ill VTE (Venous Thromboembolism) Prevention with Extended Duration Betrixaban (APEX) Trial
Authors: Alexander T Cohen, Rim Halaby, Serge Korjian, Yazan Daaboul, Donald Szlosek, Douglas Arbetter, Samuel Z. Goldhaber, Russell Hull, Adrian Hernandez, Alexander Gold, Brian Wiens, Robert Harrington, C. Michael Gibson
Journal: Blood (2016)