tbuckley/cabot-search huggingface dataset:
Effect of Graft Engineering and Post-Transplantation Immunosuppression Regimen on Immunophenotypic Recovery in Recipients of Unrelated Donor Bone Marrow (T-Cell Depletion Trial) in a Multicenter Randomized Phase II-III Trial.
Authors: Lawrence S. Lamb, John E. Wagner, Nancy A. Kernan, Trudy N. Small, Shelly L. Carter, John S. Thompson, Gretchen A. Cloud, Sreelatha Meleth, Anand Kumar, Carolyn A. Keever-Taylor
Journal: Blood (2007)
The effect of Desferasirox in expression of Adhesion molecules in Neutrophils and Monocytes, in the Platelets Activacion and in the Atherothrombosis in Patients with Mielodisplastic Syndrome (MDS) and iron Overload.
Authors: Isabel Caparros, Regina Garcia-Delgado, Arturo Campos, Ana Rosell, Ma Paz Queipo de Llano, Santiago de la Torre, Gemma Ramirez, Laura Entrena, Eulogio Conde, Santiago Del Castillo
Journal: Blood (2009)
Abstract PR05: Control of the melanoma metastatic phenotype by A-to-I microRNA editing
Authors: Einav Shoshan, Li Huang, Mayra E. Vasquez, Ho-Jeong Lee, Sun-Jin Kim, Cristina Ivan, George A. Calin, Anil K. Sood, Patrick Hwu, Jeffrey E. Gershenwald, Gal Markel, Isaiah J. Fidler, Menashe Bar-Eli
Journal: Cancer Research (2016)

Abstract Although recent studies have shown that adenosine-to-inosine (A-to-I) RNA editing occurs in microRNAs, its effects on tumor growth and metastasis are not well understood. We present evidence of CREB-mediated low expression of ADAR1 in metastatic melanoma cell lines and tumor specimens. Re-expression of ADAR1 resulted in the suppression of melanoma growth and metastasis in vivo. Consequently, we identified 3 miRs (miR-455-5P, mir-378-3P, miR-324-5P) undergoing A-to-I editing in the low-metastatic melanoma cell lines but not in highly metastatic. One of these miRs, miR-455-5P has two A-to-I RNA editing sites. The biological function of edited miR-455-5P is different from the unedited form. Indeed, w.t. miR-455 promotes melanoma metastasis via inhibition of the tumor suppressor gene CPEB1 . Moreover, w.t. miR-455 enhances melanoma growth and metastasis in vivo while the edited form inhibits these features mainly by affecting the tumor microenvironment. TCGA analysis confirmed accumulation of wild-type miR-455 in metastatic melanoma lesions. These results demonstrate a previously unrecognized role of RNA editing in melanoma progression. Citation Format: Einav Shoshan, Li Huang, Mayra E. Vasquez, Ho-Jeong Lee, Sun-Jin Kim, Cristina Ivan, George A. Calin, Anil K. Sood, Patrick Hwu, Jeffrey E. Gershenwald, Gal Markel, Isaiah J. Fidler, Menashe Bar-Eli. Control of the melanoma metastatic phenotype by A-to-I microRNA editing. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr PR05.
Tivantinib (ARQ 197) versus placebo in patients (Pts) with hepatocellular carcinoma (HCC) who failed one systemic therapy: Results of a randomized controlled phase II trial (RCT).
Authors: Lorenza Rimassa, Camillo Porta, Ivan Borbath, Bruno Daniele, Stefania Salvagni, Jean Luc Van Laethem, Hans Van Vlieberghe, Jorg Trojan, Frank T Kolligs, Alan Weiss, Nancy Barahona, Antonio Gasbarrini, Monica Lencioni, Amitkumar U. Pande, Maria Lamar, Yinpu Chen, Brian E. Schwartz, Giovanni Abbadessa, Armando Santoro
Journal: Journal of Clinical Oncology (2012)

4006 Background: Tivantinib (T) is a selective, oral inhibitor of c-Met, the tyrosine kinase receptor for hepatocyte growth factor involved in tumor cell migration, invasion, proliferation and angiogenesis. T has shown promising results in HCC in phase 1 studies as monotherapy and in combination with sorafenib. Methods: This multi-center RCT, enrolled pts with unresectable HCC, 1 failed systemic therapy, ECOG PS &lt;2. Child-Pugh B-C were excluded. Pts were randomized 2:1 to oral T {360 mg bid (A), 240 mg bid (B)} or placebo (P), stratifying by PS and vascular invasion (VI). Treatment continued until disease progression (PD) or unacceptable toxicity. RECIST 1.1 response was evaluated by CT / MRI every 6 weeks. Crossover to open-label T was allowed after PD. Primary endpoint was time to tumor progression (TTP) in the intent-to-treat (ITT) population by central radiology review. Other endpoints included disease control rate (DCR), PFS, OS, efficacy in Met+ (Met ≥ 2+ in &gt;50% of tumor at immunohistochemistry) pts, safety. Results: Characteristics of the 107 enrolled HCC pts (A= 38, B= 33, P= 36) in T/P: 58/28 male; median age 70/68; PS 0 41/21; VI 22/13; Met+ 22/15; Met- 27/13. Dose A was reduced to B in all pts due to G≥3 neutropenia (NEUT) rate. Major TTP, DCR and PFS benefits were obtained in Met+ pts, with preliminary OS trend favoring T (HR=0.47) and no detrimental effect in Met- pts. DCR (95% CI) in T/P was 44 (31-56) / 31(16-48)% for ITT and 50 (28-72) / 20 (4-48)% in Met+ pts. Most common AEs in T were asthenia (26.8%), NEUT (25.4%), low appetite (25.4%); most common drug-related AEs were NEUT (25.4%), anemia (15.5%). Most frequent drug-related serious AE was neutropenic sepsis (4.2%). Efficacy was similar in A / B with less frequent NEUT in B (21.1% / 6.1%). Final OS, PK, biomarker data will be presented. Conclusions: Compared to P, T significantly benefited second-line HCC pts, especially if Met+, with manageable safety profile at 240 mg BID. [Table: see text]
GW26-e5343 MicroRNA-17-5p, a novel vascular endothelial cell modulator, controls vascular re-endothelialization and neointimal lesion formation after vascular injury
Authors: Jing Chen, Shuo Yang, Qi Hu, Jing Bai, Changwu Xu, Xiaorong Hu, Jing Zhang, Jian Yang, Hong Jiang
Journal: Journal of the American College of Cardiology (2015)
IL‐6 trans‐signaling is essential for the development of hepatocellular carcinoma in mice
Authors: Juri Bergmann, Miryam Müller, Niklas Baumann, Manuel Reichert, Carola Heneweer, Julia Bolik, Karsten Lücke, Sabine Gruber, Antonella Carambia, Susanne Boretius, Ivo Leuschner, Thomas Becker, Björn Rabe, Johannes Herkel, F. Thomas Wunderlich, Hans‐Willi Mittrücker, Stefan Rose‐John, Dirk Schmidt‐Arras
Journal: Hepatology (2016)

Hepatocellular carcinoma (HCC) is one of the most frequent tumors worldwide with rising incidence. The inflammatory cytokine, interleukin-6 (IL-6), is a critical mediator of HCC development. It can signal through two distinct pathways: the IL-6 classic and the IL-6 trans-signaling pathway. Whereas IL-6 classic signaling is important for innate and acquired immunity, IL-6 trans-signaling has been linked to accelerated liver regeneration and several chronic inflammatory pathologies. However, its implication in liver tumorigenesis has not been addressed yet. Here, we show that IL-6 trans-signaling, but not IL-6 classic signaling, is essential to promote hepatocellular carcinogenesis by two mechanisms: First, it prevents DNA-damage-induced hepatocyte apoptosis through suppression of p53 and enhances β-catenin activation and tumor proliferation. Second, IL-6 trans-signaling directly induces endothelial cell proliferation to promote tumor angiogenesis. Consequently, soluble gp130 fused to Fc transgenic mice lacking IL-6 trans-signaling are largely protected from tumor formation in a diethylnitrosamine/3,3′,5,5′-tetrachloro-1,4-bis(pyridyloxy)benzene model of HCC. Conclusion: IL-6 trans-signaling, and not IL-6 classic signaling, is mandatory for development of hepatocellular carcinogenesis. Therefore, specific inhibition of IL-6 trans-signaling, rather than total inhibition of IL-6 signaling, is sufficient to blunt tumor initiation and impair tumor progression without compromising IL-6 classic signaling-driven protective immune responses. (Hepatology 2017;65:89-103).
Correlation Between Clinical Outcome and Disease Kinetics by Quantitative PCR in Myeloma Patients Following Post-Transplant Consolidation with Bortezomib, Thalidomide and Dexamethasone.
Authors: Marco Ladetto, Gloria Pagliano, Simone Ferrero, Federica Cavallo, Daniela Drandi, Michela Boi, Loredana Santo, Claudia Crippa, Luca De Rosa, Patrizia Pregno, Mariella Grasso, Anna Marina Liberati, Tommaso Caravita, Francesco Pisani, Tommasina Guglielmelli, Vincenzo Callea, Fausto Rossini, Pellegrino Musto, Clotilde Cangialosi, Alberto Rocci, Roberto Passera, Mario Boccadoro, Antonio Palumbo
Journal: Blood (2009)
DNA mismatch repair deficiency and benefit from adjuvant bevacizumab in NSABP C-08: Molecular profiling results.
Authors: Katherine L. Pogue-Geile, Noriko Tanaka, Patrick Gavin, Greg Yothers, Linda H. Colangelo, Chungyeul Kim, Seong-Rim Kim, Debora Fumagalli, Yusuke Taniyama, Saima Sharif, Michael J. O'Connell, Soonmyung Paik
Journal: Journal of Clinical Oncology (2012)

55 Background: The purpose of this study was to identify biomarkers that define a subset of patients who received benefit from bevacizumab (bev) in NSABP trial C-08, even though bev did not improve outcomes over standard adjuvant chemotherapy (CT) in the treatment of stage II and III colon cancer. Methods: A randomly selected cohort of C-08 cases (N=500) were profiled for whole genome expression (N=445) and for mutations (N=463) in KRAS, NRAS, PIK3CA, and MET. BRAF mutations and mismatch repair (MMR) status were profiled on the available cases (N=1,764 and 1,993, respectively). Cox proportional hazard models were used to assess prognosis and prediction for the value of bev using overall survival (0S) and time to recurrence (TTR) as end points. Results: The effect of bev was different for MMR deficient (MMR-d) and proficient tumors for OS (interaction p=.035) but not TTR (interaction p=.08). Patients with MMR-d (N=252) tumors showed a significant benefit from the addition of bev to CT for OS (hazard ratio =0.52 (95% CI: 0.29-0.94, p=0.028). KRAS, NRAS, PIK3CA, and MET were not significant for interaction with bev in the discovery cohort. BRAF mutations were associated with MMR status (p&lt;.0001) and the prognostic value of MMR depended on BRAF for TTR (interaction p=.027) but not OS (interaction p=.31). The effect of bev was independent of BRAF (interaction p=.28 TTR and .37 OS). Three-factor interaction tests for bev, MMR, and BRAF were not significant for either endpoint. Gene expression analysis with BRB array tools identified 5 BioCarta pathways (p&lt;0.05) which differentially expressed in 4 statistical tests; 4 of these pathways were directly or indirectly involved in T cell activation and one was involved in the activation of VEGF. Conclusions: Patients in C-08 with MMR-d tumors received benefit from bev treatment but these results need to be validated in a separate study. Gene expression data suggest that T-cells may be differentially expressed based on MMR status. Activation of VEGF has been shown to suppress T-cell development (Ohm et al. Blood. 2003:10;4878). A speculative possibility for the benefit of bev in MMR-d tumors may be due to blocking of VEGF, releasing T cells from VEGF suppression.
Phase I clinical and pharmacokinetic (PK) trial of the kinesin spindle protein (KSP) inhibitor MK-0731 in cancer patients
Authors: M. N. Stein, E. H. Rubin, P. D. Scott, R. Fernandez, N. G. Agrawal, K. Hsu, A. Walker, K. Holen, G. Wilding
Journal: Journal of Clinical Oncology (2006)

2001 Background: KSP is essential for the separation of spindle poles during mitosis and inhibition results in mitotic arrest. Function is thought to be limited to mitosis and inhibitors should not cause the peripheral neuropathy seen with other mitotic-inhibitors. MK-0731 is a potent inhibitor of KSP, with an IC 50 of 2.2 nM, and &gt;20,000 fold selectivity against other kinesins. MK-0731 causes mitotic arrest with an EC 50 in several tumor cell lines of 3−5 nM. Methods: Phase I study to determine the safety and tolerability, MTD, and PK of MK-0731 administered IV over 24 hrs every 21 (Q21) ds. Results: Eight pts with solid tumors (M/F 6/2), median age 55 yrs (45–72 yrs), were treated at doses of 6 to 48 mg/m 2 /24hrs. Prolonged (≥5 ds) Grade 4 neutropenia was observed in 2 pts at 48 mg/m 2 /24 hrs leading to expansion of cohorts at lower dose levels. Other drug related toxicities include diarrhea, alopecia, nail changes, nausea/vomiting, mucositis, abdominal pain, anorexia, phlebitis. PK results suggest that steady-state concentrations may not be achieved by the end of the 24 hr infusion and MK-0731 concentrations appear to decline monoexponentially or biexponentially following the infusion with terminal t 1/2 from ∼4 to 11 hrs. Median values at the 48 mg/m 2 /24 hrs dose level were C max = 1223 nM, AUC∞ = 26.585 μM · hr, and CL=122 mL/min. AUC, exposures, and end of infusion concentrations appear to increase proportionally with dose. Conclusions: This is the first study of MK-0731. The MTD was exceeded at 48 mg/m 2 /24 hrs Q21. Further evaluation will continue at lower doses. [Table: see text]
Transcription factor ETV1 is essential for rapid conduction in the heart
Authors: Akshay Shekhar, Xianming Lin, Fang-Yu Liu, Jie Zhang, Huan Mo, Lisa Bastarache, Joshua C. Denny, Nancy J. Cox, Mario Delmar, Dan M. Roden, Glenn I. Fishman, David S. Park
Journal: Journal of Clinical Investigation (2016)

Rapid impulse propagation in the heart is a defining property of pectinated atrial myocardium (PAM) and the ventricular conduction system (VCS) and is essential for maintaining normal cardiac rhythm and optimal cardiac output. Conduction defects in these tissues produce a disproportionate burden of arrhythmic disease and are major predictors of mortality in heart failure patients. Despite the clinical importance, little is known about the gene regulatory network that dictates the fast conduction phenotype. Here, we have used signal transduction and transcriptional profiling screens to identify a genetic pathway that converges on the NRG1-responsive transcription factor ETV1 as a critical regulator of fast conduction physiology for PAM and VCS cardiomyocytes. Etv1 was highly expressed in murine PAM and VCS cardiomyocytes, where it regulates expression of Nkx2-5, Gja5, and Scn5a, key cardiac genes required for rapid conduction. Mice deficient in Etv1 exhibited marked cardiac conduction defects coupled with developmental abnormalities of the VCS. Loss of Etv1 resulted in a complete disruption of the normal sodium current heterogeneity that exists between atrial, VCS, and ventricular myocytes. Lastly, a phenome-wide association study identified a link between ETV1 and bundle branch block and heart block in humans. Together, these results identify ETV1 as a critical factor in determining fast conduction physiology in the heart.
High-Level Expression of ROR1 Associates with Early Disease Progression in Patients with Chronic Lymphocytic Leukemia
Authors: Bing Cui, Liguang Chen, Laura Z. Rassenti, Emanuela M. Ghia, Jian Yu, Ling Zhang, Donna S Neuberg, William Wierda, Michael Keating, Kanti R. Rai, Neil E. Kay, Jennifer R. Brown, John C. Byrd, John Gribben, Thomas J. Kipps
Journal: Blood (2015)
Use of Scaffolding Tissue Biografts To Bolster Vesicourethral Anastomosis During Salvage Robot-assisted Prostatectomy Reduces Leak Rates and Catheter Times
Authors: Gabriel Ogaya-Pinies, Yash Kadakia, Hariharan Palayapalayam-Ganapathi, Tracey Woodlief, Cathy Jenson, Jamil Syed, Vipul Patel
Journal: European Urology (2016)
CC-122 Has Robust Anti-Proliferative Activity in a Primary Chronic Lymphocytic Leukemia (CLL) Co-Culture Model and Is Superior to Lenalidomide
Authors: Jemma Blocksidge, Mark Glenn, Anita K. Gandhi, Anke Klippel, Michael Pourdehnad, Rajesh Chopra, Nagesh Kalakonda
Journal: Blood (2014)
GW26-e1436 Effects of Ginsenoside Rb1 capsule on Homocysteine-induced endothelial dysfunction and inflammatory response
Authors: Bin Zhou, Shujie Yu, Zhenda Zheng, Lin Wu, Yong Liu, Baoshun Hao, Zhiming Song, Lin Chen, Xiaoxian Qian
Journal: Journal of the American College of Cardiology (2015)
Optical Coherence Tomography Reflective Drusen Substructures Predict Progression to Geographic Atrophy in Age-related Macular Degeneration
Authors: Malini Veerappan, Abdul-Karim M. El-Hage-Sleiman, Vincent Tai, Stephanie J. Chiu, Katrina P. Winter, Sandra S. Stinnett, Thomas S. Hwang, G. Baker Hubbard, Michelle Michelson, Randall Gunther, Wai T. Wong, Emily Y. Chew, Cynthia A. Toth, Cynthia A. Toth, Wai Wong, Thomas Hwang, G. Baker Hubbard, Sunil Srivastava, Michelle McCall, Katrina Winter, Neeru Sarin, Katherine Hall, Patti McCollum, Linda Curtis, Stefanie Schuman, Stephanie J. Chiu, Sina Farsiu, Vincent Tai, Monica Sevilla, Christopher Harrington, Randall Gunther, Du Tran-Viet, Francisco Folgar, Eric Yuan, Traci Clemons, Molly Harrington, Emily Chew
Journal: Ophthalmology (2016)
25-Oh Vitamin D, Vitamin D Receptor and Immunomodulatory Cytokines Serum Levels in Patients with Autoimmune Citopenias: Correlation with Hematologic Parameters and Clinical Severity
Authors: Bruno Fattizzo, Anna Zaninoni, Paola Bianchi, Elisa Fermo, Francesco Nesa, Wilma Barcellini
Journal: Blood (2014)
PWE-030 High definition (hd) endoscopy but not i-scan significantly increases the detection of markers of coeliac disease: a multicentre uk study: Abstract PWE-030 Table 1
Authors: M Burden, PD Mooney, N Patel, S Wong, J Teare, M Hadjivassiliou, DS Sanders
Journal: Gut (2015)

<h3>Introduction</h3> Coeliac disease (CD) remains underdiagnosed. Many patients with CD have undergone a previous endoscopy where the opportunity to make a diagnosis was missed. Clinicians may rely on endoscopic markers of CD to guide biopsy but they lack sensitivity. A routine duodenal biopsy approach may solve this problem but it is expensive. Methods to improve the detection of CD at endoscopy to guide biopsy would seem advantageous. I-Scan, a digital enhancement technique, has shown promising results. However, only one, single centre study has been performed. This was an uncontrolled, unblinded trial in high prevalence population (35% CD). We aimed to assess the utility of I-Scan in a lower prevalence population in a randomised controlled trial <h3>Method</h3> Patients from 2 UK hospitals (Royal Hallamshire Hospital, Sheffield and St. Mary’s Hospital, London) were randomised into 2 groups: Group 1 standard HD white light endoscopy (WLE) and Group 2 WLE plus I-Scan. Patients were compared to a standard non-HD WLE control group, Group 3. All patients received at least 4 duodenal biopsies. Coeliac serology was performed concurrently. The presence of endoscopic markers of CD, scalloping, mosaic pattern, nodularity, loss of duodenal folds or increased vascularity was noted and compared to VA on histology as the gold standard <h3>Results</h3> 700 patients (63% female, mean age 51.7) were recruited (201 into Group 1, 199 in Group 2 and 300 into Group 3). In total 130 (18.5%) new diagnoses of CD were made (19 in Group 1, 22 in Group 2 and 89 in Group 3). In new CD cases, endoscopic markers of CD were seen in 80.5% in the HD groups compared to 41.6% in Group 3 (p &lt; 0.0001). In Group 2, I-Scan appeared to enhance changes in 18% of new CD cases. However there was no significant difference in sensitivity between Group 1 (89.5%) and Group 2 (72.7%) (p = 0.2). Full sensitivity and specificity analysis is shown in Table 1. The severity of VA was analysed for missed cases. There was no significant difference in the distribution of VA severity across the 3 groups (p = 0.6). The use of HD/I-Scan did not prevent total VA being missed <h3>Conclusion</h3> HD endoscopy significantly increases the detection of the endoscopic markers of CD (p &lt; 0.0001). However although I-scan appears to enhance the changes of villous atrophy it does not significantly increase the detection of markers (p = 0.2) <h3>Disclosure of interest</h3> None Declared.
Differential effects of regression of electrocardiographic left ventricular hypertrophy on outcome in diabetic vs non-diabetic hypertensive patients : The LIFE study
Authors: PM Okin, E Gerdts, KE Harris, Lars H Lindholm
Journal: Circulation (2005)

Differential effects of regression of electrocardiographic left ventricular hypertrophy on outcome in diabetic vs non-diabetic hypertensive patients : The LIFE study
Growth trajectories and asthma/rhinitis in children: a longitudinal study in Taiwan
Authors: Yang-Ching Chen, Tsan-Hon Liou, Pau-Chung Chen, Bor-Luen Chiang, Yao-Hsu Yang, Hsien-Yu Fan, Yungling Leo Lee
Journal: European Respiratory Journal (2016)

Studies have reported the effect of body weight in early childhood on asthma. However, the effect of growth patterns during school age on asthma and rhinitis has yet to be explored. We sought to investigate whether various growth patterns predict incident asthma and rhinitis. We conducted a nationwide longitudinal study (Taiwan Children Health Study) in 14 Taiwanese communities. Body mass index (BMI) z-scores of 4422 children aged 6–11 years were collected annually and distinct growth trajectory classes were identified using a latent generalised mixture model. Pulmonary function and exhaled nitric oxide fraction ( F eNO ) levels were also measured. Whether different growth trajectory classes predict incident asthma and rhinitis at age 12, 15 and 18 years was determined using a discrete time hazard model. Four growth trajectory classes were identified. Persistently overweight children exhibited significantly increased risks of asthma and rhinitis at age 12 years. Furthermore, being persistently overweight had a long-term effect on incident asthma (hazard ratio 2.47, 95% CI 1.18–5.12) and rhinitis (hazard ratio 1.44, 95% CI 1.12–1.84) in adolescence and early adulthood. Children in high BMI classes exhibited significantly lower pulmonary functions compared with normal growth children. F eNO levels were lower in children in the high BMI classes and higher in children showing declining obesity compared with normal growth children. Persistently overweight children exhibited incident asthma and rhinitis in adolescence and early adulthood.