tbuckley/cabot-search huggingface dataset:
An expression-guided screen for small molecules targeting aggressive prostate cancer.
Authors: Patrick Mullane, Yukan Duan, Benjamin Benzon, Brian Simons, Paula Hurley, Zhenhua Huang, Luigi Marchionni, Ismael A. Vergara, Mohammed Alshalalfa, Elai Davicioni, Edward M. Schaeffer, Ashley Ross
Journal: Journal of Clinical Oncology (2014)

e16081 Background: Though about half of newly diagnosed prostate cancer may not require immediate treatment, it remains the second most common cause of cancer death in the United States indicating a need for novel preventive and therapeutic treatments. Here we use expression based analysis to identify “druggable” targets which were then used to tailor screens for commercially available candidate inhibitors of prostate cancer. Methods: A list of 537 differentially expressed genes was developed by comparing expression profiles of prostate cancer from men with high risk localized disease that either metastasized or was cured following radical prostatectomy. Differentially expressed genes were compared to PharmGKB and Drugbank to link them to commercially available drugs. Identified drugs were assessed for their effects on cell viability, migration and invasion in androgen responsive and independent prostate cancer cell lines and in an ex-vivo embryonic development assay of prostate epithelial invasion. Results: Putative prostate cancer inhibitors roughly grouped into anti-neoplastic agents, tyrosine kinase inhibitors, statins, beta-blockers/beta-agonists, aldosterone/ATII inhibitors, catecholamine pathway related drugs, anti-platelets, immunosuppresants, leukotriene antagonists and anti-diabetic drugs. Multiple classes of drugs inhibited cell viability in a dose-dependent manner in prostate cancer cell lines with individual inhibitors in each group having disparate effects. A subset of drugs showed significant inhibition of cell migration, including Celecoxib, Metformin, Simvastatin, Iressa and Sunitinib. In addition, inhibition of prostate cell invasion into the surrounding mesenchyme was seen with several agents including Sorafenib and Metformin. Conclusions: Use of gene expression data and bioinformatics allowed for smaller scale screening of inhibitors enriched for putative effects on prostate cancer. Through these methods we identified inhibitors already shown to effect prostate cancer and in addition currently available drugs with previously unknown effects on prostate cancer.
The prognostic value of MRI in determining reinjury risk following acute hamstring injury: a systematic review
Authors: Moniek van Heumen, Johannes L Tol, Robert-Jan de Vos, Maarten H Moen, Adam Weir, John Orchard, Gustaaf Reurink
Journal: British Journal of Sports Medicine (2017)

Background A challenge for sports physicians is to estimate the risk of a hamstring re-injury, but the current evidence for MRI variables as a risk factor is unknown. Objective To systematically review the literature on the prognostic value of MRI findings at index injury and/or return to play for acute hamstring re-injuries. Data sources Databases of PubMed, Embase, MEDLINE, Scopus, CINAHL, Google Scholar, Web of Science, LILACS, SciELO, ScienceDirect, ProQuest, SPORTDiscus and Cochrane Library were searched until 20 June 2016. Study eligibility criteria Studies evaluating MRI as a prognostic tool for determining the risk of re-injury for athletes with acute hamstring injuries were eligible for inclusion. Data analysis Two authors independently screened the search results and assessed risk of bias using standardised criteria from a consensus statement. A best-evidence synthesis was used to identify the level of evidence. Post hoc analysis included correction for insufficient sample size. Results Of the 11 studies included, 7 had a low and 4 had a high risk of bias. No strong evidence for any MRI finding as a risk factor for hamstring re-injury was found. There was moderate evidence that intratendinous injuries were associated with increased re-injury risk. Post hoc analysis showed moderate evidence that injury to the biceps femoris was a moderate to strong risk factor for re-injury. Conclusion There is currently no strong evidence for any MRI finding in predicting hamstring re-injury risk. Intratendinous injuries and biceps femoris injuries showed moderate evidence for association with a higher re-injury risk. Systematic review registration Registration in the PROSPERO International prospective register of systematic reviews was performed prior to study initiation (registration number CRD42015024620).
Abstract P6-08-06: A positive feedback loop couples CD44s and HAS2 for sustained Akt activation and tumor cell survival
Authors: S Liu, C Cheng
Journal: Cancer Research (2017)

Abstract Breast cancer is the second leading cause of cancer death in women worldwide. Despite recent advances in breast cancer treatment, tumor metastasis and recurrence remain the most significant clinical obstacles, largely due to the resistance of residual breast tumor cells to existing therapies. RNA alternative splicing is a fundamental mechanism for gene regulation and protein diversity. Despite the fact that nearly all human genes are regulated by alternative splicing, very limited studies have addressed the role of alternative splicing in tumorigenesis. Our lab uses the cell adhesion molecule CD44 as a model to investigate the role of alternative splicing in breast cancer metastasis. CD44 undergoes extensive alternative splicing, giving rise to the standard (CD44s) and variant (CD44v) isoforms. Previous work from our lab demonstrated that the CD44s isoform is required for Epithelial to Mesenchymal transition (EMT) and breast tumor metastasis. Mechanistically, we have shown that CD44s, but not CD44v, potentiates Akt signaling, promoting cell survival and chemoresistance in breast cancer cells. To better understand CD44s-mediated downstream pathways critical for breast tumor metastasis, we analyzed CD44s-dependent gene signature and identified Hyaluronan Synthase 2 (HAS2), an enzyme that produces hyaluronan (HA), as one of the most significantly upregulated genes in response to CD44s expression. Interestingly, HA is the major ligand for CD44, and HA/CD44 interaction promotes Akt activation. These results led us to test a hypothesis that a positive feedback loop, involving CD44s and HAS2, sustains Akt signaling and promotes tumor cell survival. Indeed, our results show that CD44s-mediated Akt activation stimulates HAS2 transcription. This increase in HAS2 transcription is mediated by Akt phosphorylation of FOXO1, a transcription repressor inactivated by phosphorylation. We further show that HAS2 and HA activate Akt signaling in a CD44s-dependent manner. Importantly, disruption of this feed-forward loop inhibits EMT and triggers cell death. PI3K/Akt signaling is hyperactive in more than 70% of breast tumors. Hence, the proteins involved in this positive feedback loop represent very attractive and promising drug targets for breast cancer therapy. Our work has demonstrated how aberrant expression of alternative spliced isoform in breast cancer, through a positive feedback loop, leads to sustained Akt signaling, enhanced cell survival, and a metastatic phenotype. Disrupting this positive feedback loop may provide a foundation for an innovative approach to treat metastatic breast cancer patients. Citation Format: Liu S, Cheng C. A positive feedback loop couples CD44s and HAS2 for sustained Akt activation and tumor cell survival [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-08-06.
the G516 Polymorphism of Cytochrome P450 2B6 Gene in the Susceptibility of De Novo Acute Myeloid Leukemia.
Authors: Aggeliki Daraki, Sophia Zachaki, Theodora Koromila, Maria Karakosta, Gabriel Pantelias, Vasiliki Aleporou, Constantina Sambani, Panagoula Kollia, Kalliopi Manola
Journal: Blood (2012)
Cost-effectiveness of Chagas disease screening in Latin American migrants at primary health-care centres in Europe: a Markov model analysis
Authors: Ana Requena-Méndez, Sheila Bussion, Edelweiss Aldasoro, Yves Jackson, Andrea Angheben, David Moore, Maria-Jesús Pinazo, Joaquim Gascón, Jose Muñoz, Elisa Sicuri
Journal: The Lancet Global Health (2017)

Chagas disease is currently prevalent in European countries hosting large communities from Latin America. Whether asymptomatic individuals at risk of Chagas disease living in Europe should be screened and treated accordingly is unclear. We performed an economic evaluation of systematic Chagas disease screening of the Latin American population attending primary care centres in Europe.We constructed a decision tree model that compared the test option (screening of asymptomatic individuals, treatment, and follow-up of positive cases) with the no-test option (screening, treating, and follow-up of symptomatic individuals). The decision tree included a Markov model with five states, related to the chronic stage of the disease: indeterminate, cardiomyopathy, gastrointestinal, response to treatment, and death. The model started with a target population of 100 000 individuals, of which 4·2% (95% CI 2·2-6·8) were estimated to be infected by Trypanosoma cruzi. The primary outcome was the incremental cost-effectiveness ratio (ICER) between test and no-test options. Deterministic and probabilistic analyses (Monte Carlo simulations) were performed.In the deterministic analysis, total costs referred to 100 000 individuals in the test and no-test option were €30 903 406 and €6 597 403 respectively, with a difference of €24 306 003. The respective number of quality-adjusted life-years (QALYs) gained in the test and no-test option were 61 820·82 and 57 354·42. The ICER was €5442. In the probabilistic analysis, total costs for the test and no-test option were €32 163 649 (95% CI 31 263 705-33 063 593) and €6 904 764 (6 703 258-7 106 270), respectively. The respective number of QALYs gained was 64 634·35 (95% CI 62 809·6-66 459·1) and 59 875·73 (58 191·18-61 560·28). The difference in QALYs gained between the test and no test options was 4758·62 (95% CI 4618·42-4898·82). The incremental cost-effectiveness ratio (ICER) was €6840·75 (95% CI 2545-2759) per QALY gained for a treatment efficacy of 20% and €4243 per QALY gained for treatment efficacy of 50%. Even with a reduction in Chagas disease prevalence to 0·05% and with large variations in all the parameters, the test option would still be more cost-effective than the no-test option (less than €30000 per QALY).Screening for Chagas disease in asymptomatic Latin American adults living in Europe is a cost-effective strategy. Findings of our model provide an important element to support the implementation of T cruzi screening programmes at primary health centres in European countries hosting Latin American migrants.European Commission 7th Framework Program.
Stability of Blood Eosinophils in Patients with Chronic Obstructive Pulmonary Disease and in Control Subjects, and the Impact of Sex, Age, Smoking, and Baseline Counts
Authors: Olorunfemi A. Oshagbemi, Andrea M. Burden, Dionne C. W. Braeken, Yvonne Henskens, Emiel F. M. Wouters, Johanna H. M. Driessen, Anke H. Maitland-van der Zee, Frank de Vries, Frits M. E. Franssen
Journal: American Journal of Respiratory and Critical Care Medicine (2017)
PP27. ESTABLISHMENT OF A HAEMATOPOIETIC STEM-CELL BASED THERAPY FOR BRAIN TUMOURS IN PRE-CLINICAL MOUSE MODELS
Authors: Dr Tereza Andreou, Dr Nora Rippaus, Mr David Taggart, Ms Jennifer Williams, Mr Krzysztof Wronski, Prof Susan Short, Dr Heiko Wurdak, Dr Mihaela Lorger
Journal: Neuro-Oncology (2017)
Visualization of c-Mpl Expression in Ph-Negative Myeloproliferative Diseases and So-Called Essential Thrombocythemia with Ringed Sideroblasts by Confocal Laser Scanning Microscopy.
Authors: Annette Schmitt-Graeff, Juergen Thiele, Hans M. Kvasnicka, Ulrich Germing, Michael Luebbert, Cornelius Waller, Sabine Haxelmanns, Roland Nitschke, Heike L. Pahl, Jerry L. Spivak
Journal: Blood (2004)
Cleaved High Molecular Weight Kininogen (HKa) and Kininostatin (D5) Induce Apoptosis and Inhibit Migration and Invasion of Human Prostate Cancer Cells by Preventing AKT Phosphorylation and Cyclin D1 Synthesis and Disrupting the Interaction of UPAR and EGFR.
Authors: Yuchuan Liu, Robin Pixley, Mario Fusaro, Robert W. Colman
Journal: Blood (2007)
Comprehensive Bulk and Single Cell Transcriptomic Characterization of SF3B1 Mutation Reveals Its Pleiotropic Effects in Chronic Lymphocytic Leukemia
Authors: Jean Fan, Lili Wang, Angela N Brooks, Youzhong Wan, Donna S Neuberg, Laura Z. Rassenti, Emanuela M. Ghia, Thomas J. Kipps, Jennifer R. Brown, Shuqiang Li, Kenneth J Livak, Matthew M. Meyerson, Peter V. Kharchenko, Catherine J. Wu
Journal: Blood (2015)
Low Incidence of Tumor Lysis Syndromes (TLS) and Infusion Related Reactions (IRR) in the CLL2-Bag Trial Evaluating a Sequential Treatment of Bendamustine (B), Obinutuzumab (GA101, G) and Venetoclax (ABT-199, A) in Patients with Chronic Lymphocytic Leukemia (CLL): Interim Safety Results of a Phase-II-Trial of the German CLL Study Group (GCLLSG)
Authors: Paula Cramer, Julia von Tresckow, Jasmin Bahlo, Sandra Robrecht, Anja Engelke, Petra Langerbeins, Anna-Maria Fink, Hyatt Balke-Want, Othman Al-Sawaf, Till Seiler, Ludwig Fischer von Weikersthal, Holger Hebart, Kirsten Fischer, Clemens-Martin Wendtner, Stephan Stilgenbauer, Barbara F. Eichhorst, Michael Hallek
Journal: Blood (2016)
Abstract ES3-2: Optimizing Her2- directed treatment in early stage disease
Authors: S Tolaney
Journal: Cancer Research (2017)

Abstract Amplification of HER2 is present in approximately 18-20% of all breast cancer, and targeted anti-HER2 therapies have transformed our approach for this subtype of disease. Trastuzumab-based chemotherapy remains the standard therapy for these patients, however, there remain several questions in determining the optimal treatment regimen: (1) What is the role of anthracyclines? ; (2) What is the optimal preoperative regimen?; (3) How do we treat small, node-negative HER2+ breast cancers?; (4) Should all patients receive pertuzumab, and in what setting?; (5)Does Trastuzumab-DM1 have a role in the early stage setting? This educational session will review the available data to address each of these questions, and will provide recommendations for optimizing HER2- directed therapy in the early stage setting. Citation Format: Tolaney S. Optimizing Her2- directed treatment in early stage disease [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr ES3-2.
Interim Analyses of the MMRC Reference Collection Identifies Recurrent Genomic-Level Events in Multiple Myeloma and Demonstrates That CDKN2C/p18 Deletion Is the Pre-Eminent Copy Number Alteration in Poor Prognosis Disease
Authors: Michael A Chapman, Jean-Philippe Brunet, Angela Baker, Jonathan Keats, Gregory Ahmann, Anna C Schinzel, Anna Moore, Vijayalakshmi Shanmugam, Louise M. Perkins, Daniel Auclair, William C. Hahn, P. Leif Bergsagel, Rafael Fonseca, John Carpten, Jeffrey Trent, Todd R. Golub
Journal: Blood (2008)
HBZ-mediated shift of JunD from growth suppressor to tumor promoter in leukemic cells by inhibition of ribosomal protein S25 expression
Authors: M Terol, H Gazon, I Lemasson, M Duc-Dodon, B Barbeau, R Césaire, J-M Mesnard, J-M Péloponèse Jr
Journal: Leukemia (2017)
Neurological complications of influenza.
Journal: BMJ (1970)

The initial discrepancy in the association of the Au antigen and infectious hepatitis is almost certainly due, as Krugman has suggested, to difficulties in clinical differentiation between the two forms.Patients with hepatitis without a clear-cut history of parenteral inoculations are likely to be diagnosed as of the infectious type, but this type of infection may be transmitted by the parenteral route.And what is more important, the SH, or serum, infection may be transmitted by the oral route.'3In this sense the patient's history can be misleading, but at all events the association of Au with SH antigen now seems firmly established.A report by Y. Cossart and co-workers" in Britain showed that Australia-SH antigen had been identified by similar techniques in 40% of patients with acute viral hepatitis.How does this fit in with other forms of liver disease?W. T. London and colleagues'6 found no evidence of the Au antigen in other diseases affecting the liver, including cirrhosis, infectious mononucleosis, and hepatoma.Basically similar results have been reported by R. Wright and col- leagues.'7They identified Au antigen irn 46 out of 88 patients (52%) with acute viral hepatitis, in 11 out of 29 (38%) of those with prolonged viral hepatitis, and in 6 out of 24 (25%) of those with chronic active hepatitis, and in only 3 of the remaining 248 patients with acute or chronic liver disease.G. L. Gitnick and co-workers found Au antigen in only 3 out of 31 patients with chronic active liver disease."8Although the Au-SH antigen can be found more readily in the early weeks of the disease it can undoubtedly persist for long periods," '7 even for as long as 20 years.'9That the Au-SH antigen is highly infectious there is little doubt.Studies8"4 have shown it to be transmissible.Furthermore, workers in Britain'0 have obtained positive tests for SH anti- gen from affected staff and patients after an outbreak of viral hepatitis in a haemodialysis unit.The antigen persisted for a longer period in affected patients and in one case was still positive after three years.A study from Melbourne in this week's issue of the B.M.Y.
Quantitative Monitoring of EBV Viral Load in 222 Hematopoietic Stem Cell Transplant Patients: Risk Analysis and Development of EBV-Associated Post-Transplant Lymphoproliferative Diseases (PTLD)
Authors: Jih-Luh Tang, Ming Yao, Meng-Yao Lu, Bor-Sheng Ko, Shang-Yi Huang, Chi-Cheng Li, Chien-Ting Lin, Hsin-An Hou, Shang-Ju Wu, Wen-Chien Chou, Woei Tsay, Yao-Chang Chen, Hwei-Fang Tien, Shiann-Tarng Jou, Yong-Li Yang, Dong-Tsamn Lin, Kai-Hsin Lin
Journal: Blood (2011)
Effects of Advice to Drink 8 Cups of Water per Day in Adolescents With Overweight or Obesity
Authors: Julia M. W. Wong, Cara B. Ebbeling, Lisa Robinson, Henry A. Feldman, David S. Ludwig
Journal: JAMA Pediatrics (2017)

Health care professionals commonly recommend increased water consumption, typically to 8 cups per day, as part of a weight-reducing diet. However, this recommendation is based on limited evidence and virtually no experimental data from the pediatric population.To compare 2 standardized weight-loss diets among adolescents with overweight or obesity, either with or without additional advice and behavioral support to increase habitual water intake to 8 cups per day.A randomized clinical, parallel-group trial was conducted between February 2, 2011, and June 26, 2014, at Boston Children's Hospital, Boston, Massachusetts, among 38 adolescents with overweight or obesity who reported drinking 4 cups or less of water per day.All participants in both groups received similar weight-reducing interventions, differentiated by advice about water intake (the water group received advice to increase water intake to 8 cups per day; the control group did not receive such advice) but controlled for other dietary recommendations and treatment intensity. The interventions included dietary counseling, daily text messages, and a cookbook with health guides. To support adherence to 8 cups of water per day, the water group received well-defined messages about water through counseling and daily text messages, a water bottle, and a water pitcher with filters.The primary outcome was 6-month change in body mass index z score. Data analyses followed the intention-to-treat principle.All 38 participants (27 girls and 11 boys; mean [SD] age, 14.9 [1.7] years) completed the study. Both groups reported drinking approximately 2 cups of water per day at baseline. Self-reported change in water intake at 6 months was greater in the water group (difference from baseline, 2.8 cups per day [95% CI, 1.8 to 3.8]; P < .001) compared with that in the control group (difference from baseline, 1.2 cups per day [95% CI, 0.2 to 2.2]; P = .02) (difference between groups, 1.6 cups per day [95% CI, 0.2 to 3.0 cups per day]; P = .03). The 6-month change in body mass index z score did not differ between the water group (difference from baseline, -0.1 [95% CI, -0.2 to -0.0]; P = .005) and the control group (difference from baseline, -0.1 [95% CI, -0.2 to -0.0]; P = .008) (difference between groups, -0.0 [95% CI, -0.1 to 0.1]; P = .88).Advice and behavioral supports to consume 8 cups of water per day in the context of a weight-reducing diet did not affect body weight among adolescents with overweight or obesity. Despite intensive behavior supports, few adolescents achieved the target of 8 cups of water per day. Environmental interventions to reduce barriers to water consumption at school may be necessary in future research of the feasibility and effectiveness to achieve the target of an intake of 8 cups of water per day in adolescents.clinicaltrials.gov Identifier: NCT01044134.
Na+/HCO3 – Cotransporter NBCn2 Mediates HCO3 − Reclamation in the Apical Membrane of Renal Proximal Tubules
Authors: Yi-Min Guo, Ying Liu, Mei Liu, Jin-Lin Wang, Zhang-Dong Xie, Kang-Jing Chen, Deng-Ke Wang, Rossana Occhipinti, Walter F. Boron, Li-Ming Chen
Journal: Journal of the American Society of Nephrology (2017)

The kidney maintains systemic acid-base balance by reclaiming from the renal tubule lumen virtually all HCO3- filtered in glomeruli and by secreting additional H+ to titrate luminal buffers. For proximal tubules, which are responsible for about 80% of this activity, it is believed that HCO3- reclamation depends solely on H+ secretion, mediated by the apical Na+/H+ exchanger NHE3 and the vacuolar proton pump. However, NHE3 and the proton pump cannot account for all HCO3- reclamation. Here, we investigated the potential contribution of two variants of the electroneutral Na+/HCO3- cotransporter NBCn2, the amino termini of which start with the amino acids MCDL (MCDL-NBCn2) and MEIK (MEIK-NBCn2). Western blot analysis and immunocytochemistry revealed that MEIK-NBCn2 predominantly localizes at the basolateral membrane of medullary thick ascending limbs in the rat kidney, whereas MCDL-NBCn2 localizes at the apical membrane of proximal tubules. Notably, NH4Cl-induced systemic metabolic acidosis or hypokalemic alkalosis downregulated the abundance of MCDL-NBCn2 and reciprocally upregulated NHE3 Conversely, NaHCO3-induced metabolic alkalosis upregulated MCDL-NBCn2 and reciprocally downregulated NHE3 We propose that the apical membrane of the proximal tubules has two distinct strategies for HCO3- reclamation: the conventional indirect pathway, in which NHE3 and the proton pump secrete H+ to titrate luminal HCO3-, and the novel direct pathway, in which NBCn2 removes HCO3- from the lumen. The reciprocal regulation of NBCn2 and NHE3 under different physiologic conditions is consistent with our mathematical simulations, which suggest that HCO3- uptake and H+ secretion have reciprocal efficiencies for HCO3- reclamation versus titration of luminal buffers.