tbuckley/cabot-search huggingface dataset:
PTPS-10REPURPOSING CHEMOTHERAPY DRUGS FOR NEW APPLICATIONS IN CHILDREN'S BRAIN TUMOURS: PRECLINICAL SCREENING WITH AN IN VITRO 3D MODEL
Authors: Delyan Ivanov, David Walker, Terry Parker, Marianne Ashford, Paul Gellert, Cameron Alexander, Martin Garnett
Journal: Neuro-Oncology (2015)

BACKGROUND: While novel targeted therapeutics hold great promise in precisely eliminating sensitive subsets of tumour cells, their selectivity may lead to the proliferation of resistant clones and tumour recurrence. In this respect enhancing the distribution of less-selective, older-generation chemotherapeutics may result in improved tumour control and more favourable side effects profile. To this end we are exploring strategies relying on nanoparticle transport of drugs, intra-cavitary and metronomic intra-CSF drug delivery in order to maximise the cytotoxic effect and minimize the toxicity of chemotherapy in paediatric brain tumours. Human-based 3D in vitro models showing both safety and efficacy were established and a number of drug delivery strategies were tested for improved selectivity against medulloblastoma compared to normal human foetal brain tissue. METHODS: The topoisomerase inhibitors etoposide and teniposide were encapsulated in Poly(ethylene glycol)-block-poly(ɛ-caprolactone) (PEG-PCL 5kDa-5kDa) nanoparticles using the solvent-emulsification method. Comparative toxicity towards normal and tumour human cells was determined by treating normal and tumour spheroids with empty nanoparticles, drug-loaded nanoparticles or free drug. Spheroid volume and metabolism dose-response curves were compared between the different formulations. RESULTS: The more lipophilic drug, teniposide, showed higher drug loading (8%w/w) compared to etoposide (0.4%w/w) in the purified nanoparticles. Whereas both drugs exhibited toxicity towards proliferating cells regardless of whether those were normal or tumour, etoposide had a narrow therapeutic window of 3-10 µM where normal brain tissue showed higher viability compared to medulloblastoma cells. In addition, the teniposide-loaded nanoparticles were 1.5 times less toxic to normal tissue and equally cytotoxic to tumour cells compared to free teniposide. CONCLUSIONS: The tumour-selective therapeutic levels of 3-10 µM identified for etoposide can be useful for intra-CSF prophylaxis against distant metastasis. Although the teniposide-loaded nanoparticles offered an incremental improvement in the therapeutic index of teniposide future formulations with optimised release profile or covalently linked drug may yield better results.
Possible role of elevated phosphoSTAT5a in 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine-induced rat mammary gland carcinomas.
Authors: Andriana D. Papaconstantinou, Elizabeth G. Snyderwine
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

5131 

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a heterocyclic amine found in cooked meat that is a mammary gland carcinogen in rats. Through immunohistochemical staining, we observed two populations of PhIP-induced rat mammary gland carcinomas that could be distinguished by high or low levels of nuclear STAT5a expression. STAT5a, a transcription factor activated by phosphorylation and translocation to the nucleus, is known to regulate proliferation, differentiation, and apoptosis in the normal mammary gland. Herein we sought to determine whether there were differences in proliferation and apoptosis in carcinomas showing high and low phosphoSTAT5a expression. Mammary gland carcinomas were classified into two groups based on the levels of phosphorylated STAT5a as determined by immunoprecipitation analysis. Carcinomas with phosphoSTAT5a levels not statistically different from normal mammary gland were classified as having low phosphoSTAT5a. Carcinomas designated as having high phosphoSTAT5a showed at least 3-fold higher levels of expression than normal mammary gland. Carcinomas with high phosphoSTAT5a showed statistically higher proliferation, as demonstrated by a 5-fold higher percentage of MIB5 positive cells by immunostaining (22.7% versus 4.2% of carcinoma epithelial cells) and a 3-fold higher expression of cyclin D1 as determined by Western blot analysis. Carcinomas with elevated phosphoSTAT5a also showed lower apoptosis as determined by the TUNEL assay and by an elevated Bcl-2 (anti-apoptotic) to Bax (pro-apoptotic) protein ratio. The percentage of apoptotic cells was 0.4% and 1.2% in carcinomas with low and high phosphoSTAT5a, respectively. The Bcl-2/Bax ratio was 3.5-times higher in tumors with high phosphoSTAT5a as determined by Western blotting. Carcinoma growth as determined by the ratio of proliferating to apoptotic cells was statistically significantly higher in carcinomas with high phosphoSTAT5a. Furthermore, carcinomas with elevated phosphoSTAT5a showed a 2.5-fold higher protein expression of estrogen receptor α (ERα). ERα expression in PhIP-induced carcinomas is also known to correlate with proliferation. The results of the study suggest that in this rat mammary gland model, phosphorylation and activation of STAT5a is associated with carcinomas showing enhanced growth and proliferation.
OUTCOME of Unrelated DONOR BONE MARROW TRANSPLANTATION for THALASSEMIA MAJOR PATIENTS
Authors: Franco Locatelli, Roberto Littera, Daria Pagliara, Benedetta Contoli, Giovanna Giorgiani, Maria Ester Bernardo, Angela Mastronuzzi, Eugenia Piras, Maria Grazia Orofino, Claudio Giardini, Carlo Carcassi, Giorgio La Nasa
Journal: Blood (2011)
PTH-102 Acute Variceal Haemorrhage in The Northwest of England: Patient Characteristics, Management and Outcomes
Authors: M Bhalme, CS Kwok
Journal: Gut (2016)

<h3>Introduction</h3> Acute variceal haemorrhage (AVH) is associated with significant mortality risk. We conducted a prospective audit of patients admitted with AVH in the Northwest (NW) of England to examine our clinical practice and patient outcomes. <h3>Methods</h3> We undertook a prospective multi-centre audit of AVH related admissions to 12 NW hospitals between November 2011 to April 2012. Data on patient characteristics, management and outcomes were collated by reviewing hospital records. Adherence with Baveno V consensus guidelines was examined. The findings were compared with 2007 UK Comparative Audit of Upper Gastrointestinal Bleeding (AUGIB).<sup>1</sup> Data analysis was performed by considering the frequency distribution of variables and their association with in-hospital mortality and length of stay. <h3>Results</h3> 102 patients (median age 53 years, 67% male) details were available. More than half the patients were admitted out-of-hours (57%) and 28% were admitted on weekends. The median time to gastroscopy was 1 (IQR 0–1.5) day. Majority of patients were managed by a gastroenterologist (88%) and received Terlipressin (75%) and antibiotics (64%). The median length of stay was 8 (IQR 5–14) days and 13% of patients died during their hospitalisation. The rate of failure to control bleeding within 120 hours was 17% and 19% of the patients had a re-bleed. In total, 5% had Sengstaken tube insertion and 7% had emergency TIPSS insertion. Age over 65 years (p = 0.008) and admission out-of-hours (p = 0.03) was associated with a higher mortality. Failure to control bleeding within 120 hours (p &lt; 0.001) and re-bleeding (p = 0.007) were also associated with increased mortality. Significantly less mortality was observed in patients that were managed by a gastroenterologist (42% versus 9%, p = 0.002). Encephalopathy was associated with a significantly prolonged length of stay (18.2 versus 10 days, p = 0.0002) as was admission to HDU/ICU (19.6 versus 9.2 days, p = 0.0001). There was no difference in length of stay based on admission out-of-hours, inpatient management by gastroenterologist, use of terlipressin, use of antibiotics and re-bleeding. <h3>Conclusion</h3> The mortality rate, length of hospital stay, use of terlipressin, prophylactic antibiotics, and therapeutic interventions at endoscopy to control AVH appeared to be better than 2007 UK AUGIB report. However, timeliness of endoscopic intervention and adherence to standard guidelines remained deficient in parts across the region. The development of a NW England regional AVH care bundle consisting of an agreed protocol and pathway for emergency TIPSS may help improve patient outcomes. <h3>Reference</h3> 1 Hearnshaw SA, <i>et al</i>. Acute upper gastrointestinal bleeding in the UK: patient characteristics, diagnoses and outcomes in the 2007 UK audit. <i>Gut.</i> 2011;60(10):1327–35. <h3>Disclosure of Interest</h3> None Declared
Strong BCL10 Nuclear Expression Identifies Gastric MALT Lymphomas That Do Not Respond to H. pylori Eradication.
Authors: Hongtao Ye, Liping Gong, Hongxiang Liu, Agnes Ruskone-Fourmestraux, Daphne de Jong, Stefano Pileri, Christian Thiede, Anne Lavergne, Henk Boot, Giancarlo Caletti, Thomas Wundisch, Thierry Molina, Babs G. Taal, Sabattini Elena, Andreas Neubauer, Kenneth A. MacLennan, Reiner Siebert, Ellen D. Remstein, Ahmet Dogan, Ming-Qing Du
Journal: Blood (2005)
Gene Expression Profiling Identifies Genes Associated with In Vitro Resistance to Daunorubicin and Cytarabine in Children with De Novo Acute Myelogenous Leukemia (AML) from the Pediatric Oncology Group (POG) Study # 9421.
Authors: Dennis J. Kuo, Norman J. Lacayo, Steven Buck, Ron Yu, Chitra Saraiya, Lorrie Douglas, Howard Weinstein, Myron Chang, Cheryl L. Willman, Robert Tibshirani, Gary V. Dahl, Branimir Sikic, Yaddanapudi Ravindranath
Journal: Blood (2004)
AB0711 Body Mass Index Is Related with The Presence of Syndesmophyte in Axial Spondyloarthritis: Data from Korean College of Rheumatology Biologics (KOBIO) Registry Cohort
Authors: S.-K. Kim, J.-Y. Choe, S.-S. Lee, K. Shin
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Given that obesity might have a potent role in the regulation of the inflammatory response of spinal or peripheral joints in axial spondyloarthritis (axSpA), the detailed relationships between obesity and disease symptoms and activity should be addressed in patients with SpA <h3>Objectives</h3> We cross-sectionally investigated whether body mass index (BMI) is associated with parameters of disease activity and clinical manifestations in axSpA. <h3>Methods</h3> Demographic, clinical, and radiological features and disease activity indexes from 789 axSpA patients (619 males and 170 females) were obtained from the Korean College of Rheumatology Biologics (KOBIO) registry cohort. BMI (kg/m<sup>2</sup>) was classified into normal (BMI &lt;23.0), overweight (23.0 ≤ BMI &lt;25.0), and obese (BMI ≥25.0). Disease activity indexes included ESR, CRP, ASDAS, BASDAI, and BASFI. <h3>Results</h3> The mean BMI in patients with axSpA was 23.8± 13.3. 50.2% of all patients were overweight or obese. Overweight/obese female patients showed higher ESR, CRP, ASDAS-ESR, and ASDAS-CRP than normal patients (p=0.045, p=0.011, p=0.035, and p=0.029, respectively). Patients with ASDAS score ≥2.1 showed higher BMI than patients with ASDAS score &lt;2.1 (p=0.019). A greater increase in BMI was noted in patients with syndesmophyte than in those without syndesmophyte (p&lt;0.001). Multivariate regression analysis showed that increased BMI was closely related with presence of syndesmophyte (β=0.932, p=0.002). In addition, syndesmophyte was found to be influenced by BMI (OR=1.087, 95% CI 1.033–1.145, p=0.007) <h3>Conclusions</h3> Our results imply that increased BMI was related with presence of syndesmophyte and in part associated with disease activity in axSpA. <h3>References</h3> Ajeganova S, Andersson ML, Hafström I; BARFOT Study Group. Association of obesity with worse disease severity in rheumatoid arthritis as well as with comorbidities: a long-term followup from disease onset. Arthritis Care Res (Hoboken) 2013;65:78–87. Ottaviani S, Allanore Y, Tubach F, Forien M, Gardette A, Pasquet B, et al. Body mass index influences the response to infliximab in ankylosing spondylitis. Arthritis Res Ther 2012;14:R115. Gremese E, Bernardi S, Bonazza S, Nowik M, Peluso G, Massara A, et al. Body weight, gender and response to TNF-α blockers in axial spondyloarthritis. Rheumatology (Oxford) 2014;53:875–81. <h3>Disclosure of Interest</h3> None declared
Erratum: Corrigendum: Evidence of innate lymphoid cell redundancy in humans
Authors: Frédéric Vély, Vincent Barlogis, Blandine Vallentin, Bénédicte Neven, Christelle Piperoglou, Thibaut Perchet, Maxime Petit, Nadia Yessaad, Fabien Touzot, Julie Bruneau, Nizar Mahlaoui, Nicolas Zucchini, Catherine Farnarier, Gérard Michel, Despina Moshous, Stéphane Blanche, Arnaud Dujardin, Hergen Spits, Jörg H W Distler, Andreas Ramming, Capucine Picard, Rachel Golub, Alain Fischer, Eric Vivier
Journal: Nature Immunology (2016)
Anticipated Diagnosis of Adverse Events after Stem Cell Transplantation Using Highly Sensitive STR-PCR for Chimerism Quantification.
Authors: Paola Nava, Ainhoa Simon, Gema Gonzalez-Pardo, Jose L. Jimenez, Milagros Gonzalez-Rivera, Pascual Balsalobre, Rafael Carrion, David Serrano, Alfonso Gomez-Pineda, Jose L. Diez-Martin, Ismael Buño
Journal: Blood (2004)
Protein Z Dependent Protease Inhibitor Inhibition of Factor XIa Is Accelerated by Unfractionated Heparin in the Presence and Absence of Protein Z: Further Evidence of the Potential Significance of XIa Inhibitory Activity.
Authors: Laura Young, Neil Van de Water, Paul L Harper, Paul A. Ockelford, Anita Horvath, Paul Coughlin, Peter Browett
Journal: Blood (2008)
PTU-117 Screening for Coeliac Disease in Irritable Bowel Syndrome Is Still Worthwhile: An Updated Systematic Review and Meta-Analysis
Authors: AJ Irvine, AC Ford, WD Chey
Journal: Gut (2016)

<h3>Introduction</h3> Coeliac disease (CD) and irritable bowel syndrome (IBS) may share similar symptoms, including bloating, abdominal pain, and diarrhoea. A previous meta-analysis demonstrated the prevalence of CD was higher in patients with IBS than controls without IBS, but recent studies have cast doubt on this. We therefore updated our previous meta-analysis. <h3>Methods</h3> MEDLINE and EMBASE were searched from 2008 (the date of a previous meta-analysis) up to February 2016. Relevant case series and case-control studies with unselected adults with IBS (+/- controls) were reviewed. IBS diagnosis was based on specific symptom-based criteria, physician’s opinion, or questionnaire data. Tests for CD included IgA antigliadin antibodies (AGA), tissue transglutaminase antibodies (tTG), endomysial antibodies (EMA), or dudoenal (D2) biopsies after positive IgA AGA, tTG, or EMA. The proportion of individuals meeting criteria for IBS testing positive for CD was combined, to give a pooled prevalence in all studies. For case-control studies the prevalence of a positive test for CD in both cases with IBS and controls without IBS were compared using odds ratios (OR) with a 95% confidence interval (CI). <h3>Results</h3> 10 studies used IgA AGAs to screen for CD in 4525 subjects, 2094 of whom had IBS. Pooled prevalence of positive IgA AGAs in IBS subjects was 5.7% (95% CI 1.7% to 11.8%). 7 of these were case-control studies and the odds ratio for a positive IgA AGA in 1530 IBS cases, compared with 2430 controls, was 2.97 (95% CI 1.42 to 6.18). 32 studies used EMA or tTG in 14150 subjects, 8219 of whom had IBS. Pooled prevalence of positive EMA or tTG was 2.6% (95% CI 1.6% to 3.8%). 12 of these were case-control studies and the odds ratio for a positive EMA or tTG in the 2677 IBS cases compared with 5931 controls was 2.60 (95% CI 1.41 to 4.79). 23 studies followed positive coeliac serology of any type with the offer of duodenal biopsy in 9784 individuals, 6991 of whom met criteria for IBS. Pooled prevalence of biopsy-proven CD in these studies was 3.3% (95% CI 2.3% to 4.5%). 8 of these were case-control studies and the odds ratio for biopsy-proven CD in 2025 IBS subjects compared with 2793 controls was 3.96 (95% CI 2.06 to 7.59). <h3>Conclusion</h3> Screening for CD in people with symptoms compatible with IBS is still worthwhile. Between 2.6% and 5.7% will have a positive serological test for CD, and 3.3% will have biopsy-proven CD. In all instances, the prevalence was significantly higher than in controls without IBS-type symptoms. <h3>Disclosure of Interest</h3> None Declared
Regulation of Natural Killer Cell Responses By Dendritic Cells Via Lymphotoxin-Alpha, Interleukin-12, and Tumor Growth Factor-Beta
Authors: Dhifaf Sarhan, Marzia Palma, Yumeng Mao, Lars Adamson, Rolf Kiessling, Håkan Mellstedt, Anders Österborg, Andreas Lundqvist
Journal: Blood (2014)
Inhibition of MALT1 Protease Activity Is Selectively Toxic for Activated B CellÃ,Â–Like Diffuse Large B Cell Lymphoma Cells.
Authors: Uta Ferch, Bernhard Kloo, Andreas Gewies, Vera Pfaender, Michael Düwel, Christian Peschel, Daniel Krappmann, Jürgen Ruland
Journal: Blood (2009)
A Phase II Study of Twice Daily Cytarabine and Fludarabine and Gentuzumab Ozogamycin (GO) In Patients (pts) with Acute Myeloid Leukemia (AML) and High-Risk Myelodysplastic Syndrome (MDS)
Authors: Elias Jabbour, Guillermo Garcia-Manero, Hady Antoine Ghanem, Farhad Ravandi, Stefan Faderl, Jorge Cortes, Ardes S. Reyes, Susan O'Brien, Gautam Borthakur, Tapan Kadia, Jan A. Burger, Marina Konopleva, Hagop M. Kantarjian
Journal: Blood (2010)
Combining Molecularly Targeted Agents: Is More Always Better?
Authors: Raghav Sundar, Nicola Valeri, Kevin J. Harrington, Timothy A. Yap
Journal: Clinical Cancer Research (2016)

The concurrent targeting of critical nodes along key signaling pathways with molecularly targeted agents is a rational antitumor strategy, which has had varying degrees of success. Combinatorial challenges include overcoming synergistic toxicities and establishing whether combinations are truly active, to make "go, no-go" decisions to proceed to later phase trials.
Distinct biological subtypes and patterns of genome evolution in lymphoma revealed by circulating tumor DNA
Authors: Florian Scherer, David M. Kurtz, Aaron M. Newman, Henning Stehr, Alexander F. M. Craig, Mohammad Shahrokh Esfahani, Alexander F. Lovejoy, Jacob J. Chabon, Daniel M. Klass, Chih Long Liu, Li Zhou, Cynthia Glover, Brendan C. Visser, George A. Poultsides, Ranjana H. Advani, Lauren S. Maeda, Neel K. Gupta, Ronald Levy, Robert S. Ohgami, Christian A. Kunder, Maximilian Diehn, Ash A. Alizadeh
Journal: Science Translational Medicine (2016)

Patients with diffuse large B cell lymphoma (DLBCL) exhibit marked diversity in tumor behavior and outcomes, yet the identification of poor-risk groups remains challenging. In addition, the biology underlying these differences is incompletely understood. We hypothesized that characterization of mutational heterogeneity and genomic evolution using circulating tumor DNA (ctDNA) profiling could reveal molecular determinants of adverse outcomes. To address this hypothesis, we applied cancer personalized profiling by deep sequencing (CAPP-Seq) analysis to tumor biopsies and cell-free DNA samples from 92 lymphoma patients and 24 healthy subjects. At diagnosis, the amount of ctDNA was found to strongly correlate with clinical indices and was independently predictive of patient outcomes. We demonstrate that ctDNA genotyping can classify transcriptionally defined tumor subtypes, including DLBCL cell of origin, directly from plasma. By simultaneously tracking multiple somatic mutations in ctDNA, our approach outperformed immunoglobulin sequencing and radiographic imaging for the detection of minimal residual disease and facilitated noninvasive identification of emergent resistance mutations to targeted therapies. In addition, we identified distinct patterns of clonal evolution distinguishing indolent follicular lymphomas from those that transformed into DLBCL, allowing for potential noninvasive prediction of histological transformation. Collectively, our results demonstrate that ctDNA analysis reveals biological factors that underlie lymphoma clinical outcomes and could facilitate individualized therapy.
VRS2 regulates hormone-mediated inflorescence patterning in barley
Authors: Helmy M Youssef, Kai Eggert, Ravi Koppolu, Ahmad M Alqudah, Naser Poursarebani, Arash Fazeli, Shun Sakuma, Akemi Tagiri, Twan Rutten, Geetha Govind, Udda Lundqvist, Andreas Graner, Takao Komatsuda, Nese Sreenivasulu, Thorsten Schnurbusch
Journal: Nature Genetics (2016)
Chenodeoxycholic acid induced changes in the expression of microRNAs and genes involved in lipid, bile acid and drug metabolism in human hepatocytes
Authors: Gerd A. Kullak-Ublick, Regina Krattinger, Serene M. Lee, Wolfgang E. Thasler, Jessica Mwinyi
Journal: Hepatology (2015)

Chenodeoxycholic acid induced changes in the expression of microRNAs and genes involved in lipid, bile acid and drug metabolism in human hepatocytes
Sirolimus, Tacrolimus and Antithymocyte Globulin Are Associated with Improved Overall Survival When Compared to Methotrexate, Tacrolimus and Antithymocyte Globulin in Mismatched Unrelated Allogeneic Hematopoietic Cell Transplantation
Authors: Rebecca Nelson, Janelle Perkins, Jamie Shapiro, Jongphil Kim, Binglin Yue, Claudio Anasetti, Mohamed A Kharfan-Dabaja
Journal: Blood (2014)
Comparative Effectiveness of Azacitidine Versus Decitabine for the Treatment of Myelodysplastic Syndromes
Authors: Tea Reljic, Neera Bhansali, Rami S. Komrokji, Karen Lin, Alan F. List, Benjamin Djulbegovic, David A. Fenstermacher, Jeffrey E. Lancet, Branko Miladinovic, Ambuj Kumar
Journal: Blood (2010)
Impaired Lentiviral Transgene Expression In Vivo Caused by Massive Methylation of SFFV Promoter Sequences.
Authors: Friederike Herbst, Claudia R Ball, Francesca Tuorto, Wei Wang, Ulrich Kloz, Frank van der Hoeven, Frank Lyko, Christof Von Kalle, Hanno Glimm
Journal: Blood (2010)
Targeting Notch and Hedgehog Embryonic Signaling Pathways Has Potent Anti-Tumor Activity in Myeloma and Is Effective in Myeloma Bone Disease.
Authors: Rolf Schwarzer, Nicole Schünemann, David M Wong, Bjarne Bogen, Kurt Bommert, Bernd Dörken, Rudolf Manz, Franziska Jundt
Journal: Blood (2012)
In Vitro and In Vivo Effects of CT-011, a Humanized Anti–PD-1 Monoclonal Antibody, in Combination with Rituximab against Human B-Cell Lymphomas.
Authors: Fuliang Chu, Myriam Foglietta, Hong Qin, Rakesh Sharma, Qing Yi, Galina Rodionov, Rinat Rotem-Yehudar, Sattva Neelapu
Journal: Blood (2009)