tbuckley/cabot-search huggingface dataset:
100. Multifunctional Drug Enhances rAAV-Mediated Transgene Expression Through Different Mechanisms in Different Cell Types
Authors: Zifei Yin, Yuan Wang, Yuanhui Zhang, Ricky Ashby, Maria Fajardo-Ashby, George Aslanidi, Changquan Ling, Arun Srivastava, Chen Ling
Journal: Molecular Therapy (2015)

Several groups have demonstrated that a number of naturally occurring compounds can significantly enhance the therapeutic efficacy of viral vectors, especially recombinant AAV vectors (Ren et al., Neurosci Lett. 479(3): 187-91, 2010; Zhang et al., Gene Ther. 18(2): 128-34, 2011; Mitchell et al., J Virol. 87(8): 4571-83, 2013; Wang et al., J Integr Med. 12(1): 20-34, 2014). In our recently published studies (Ling et al., Hum Gene Ther. 25(12): 1023-34, 2014), we provided further evidence of enhanced efficacy of a combinatorial approach involving drug-mediated chemotherapy and rAAV vector-mediated cancer gene therapy to target human hepatocellular carcinoma. In these studies, we identified that shikonin, a naphthoquinone, inhibits human liver tumor growth as well as significantly enhances the efficacy of rAAV vectors carrying a therapeutic gene, tricosanthin (TCS), in a murine xenograft model in vivo. Although our initial mechanistic studies suggested that shikonin-mediated enhancement of rAAV vector transduction was through its proteasome inhibitory activity, which was similar to that of MG132, a specific proteasome inhibitor. However, no further increase was observed when cells were co-treated with both shikonin and MG132. Since shikonin is a multifunctional compound, we wished to evaluate its effect on rAAV vector-mediated transgene expression in additional human cell types. In a human erythroleukemia cell line, K562, frequently used as a model for hematopoietic cell transduction studies, shikonin enhanced the transduction efficiency of various rAAV serotype vectors by up to 10-fold. Surprisingly, however, MG132 had no effect in K562 cells, even at the highest concentration that did not induce cytotoxicity. Thus, in a systematic study, various proteasome and protease inhibitors were evaluated. Western blot assays for the detection of polyubiquitinated total cellular proteins were performed to confirm the effectiveness of these drugs in K562 cells. Whereas carfilzomib only had a modest effect (<2-fold enhancement), surprisingly, bortezomib significantly reduced the AAV vector-mediated transgene expression in K562 cells. E-64 and PMSF, a cysteine and a serine protease inhibitor, respectively, also had no effect. Additional studies revealed that a specific inhibitor of the reactive oxygen species (ROS) formation, blocked the enhancing effect of shikonin on rAAV vector-mediated transgene expression in K562 cells but not other cell types. Furthermore, shikonin treatment did augment rAAV vector-mediated transduction ex vivo in both mouse and human primary hematopoietic stem cells. Taken together, our studies also emphasize the need to exercise caution in interpreting rAAV vector-mediated transgene expression data among different cell types involving the use of multifunctional drugs.
Description of amifostine administration among diverse sites participating in an observational registry
Authors: M. Kozloff, R. Wang, R. Jagetia, D. P. Miller, H. H. Colwell, J. Hill, R. Sneeringer, J. Trotter, C. P. Belani
Journal: Journal of Clinical Oncology (2004)

8182 Background: The Evaluating Cytoprotection Health Outcomes (ECHO) Registry, a prospective study of patients (pts) receiving amifostine prior to radiation and/or chemotherapy, collects both clinical (efficacy and toxicity) and outcomes (resource utilization, humanistic) information from pts and physicians. Data collected will allow for an accurate description of administration patterns of amifostine among various physician groups. Methods: Physicians were stratified as experienced (E) or new (N) users by having treated > 30 pts or ≤ 30 pts within the past 5 years with amifostine. Dose and route of administration were collected for 1,151 scheduled administrations of amifostine to 230 pts at 43 centers. Descriptive statistics are reported without p-values because each dose is not an independent observation. Results:Most physicians, regardless of practice type and extent of prior use, are utilizing a fixed dose of 500 mg. For chemotherapy pts (CP), for whom 73% of treatments are for prevention of renal toxicities, this corresponds to approximately 300 mg/m2, substantially lower than the suggested 740 mg/m2 dose. Only E users are administering doses higher than 500 mg. In addition, E usually administer amifostine intravenously to CP, while more than half of the doses given by N are administered as 2 SC injections. Conclusions: Further research is required to understand pt outcomes in relation to SC administration and the fixed dose of 500mg. Based on that research, new guidelines and user education may be warranted. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration MedImmune MedImmune
RNAi Screening of the Human Kinome Identifies Inhibition of WEE1 Kinase As Potent and Universal Sensitizing Target to Cytarabine in Leukemias
Authors: Raoul Tibes, Leena Chaudhuri, James M Bogenberger, Tanner R Hagelstrom, Amanda McNally, Donald Chow, Megan E Buechel, Irma Gonzales, Esteban Braggio, Hongwei Yin, Shilpi Arora, David Azorsa, Craig B. Reeder, Pierre Noel, James L. Slack, Ruben A. Mesa, Tim Demuth
Journal: Blood (2011)
Thrombosis in Patients with Paroxysmal Nocturnal Hemoglobinuria.
Authors: Regis Peffault de Latour, Jean-Yves Mary, Celia Slanoubat, Louis Terriou, Gabriel Etienne, Mohamad Mohty, Sophie Roth, Sophie de Guibert, Jean-Yves Cahn, Gerard Socié
Journal: Blood (2007)
A Glycomics-Based Test Predicts the Development of Hepatocellular Carcinoma in Cirrhosis
Authors: Xavier Verhelst, Dieter Vanderschaeghe, Laurent Castéra, Tom Raes, Anja Geerts, Claire Francoz, Roos Colman, François Durand, Nico Callewaert, Hans Van Vlierberghe
Journal: Clinical Cancer Research (2016)

Purpose: Cirrhosis is a major risk factor for the development of hepatocellular carcinoma but remains underdiagnosed in the compensated stage. Fibrosis progression and cirrhosis are associated with changes in blood serum glycomic profiles. Previously, the serum glycomics-based GlycoCirrhoTest was shown to identify 50% to 70% of compensated cirrhosis cases in chronic liver disease cohorts, at >90% specificity. This study assessed GlycoCirrhoTest for the risk of hepatocellular carcinoma development in compensated cirrhosis.Experimental Design: Serum glycomics were analyzed in sera of 133 patients, with compensated cirrhosis collected between 1995 and 2005 in a surveillance protocol for hepatocellular carcinoma using an optimized glycomic technology on a DNA sequencer.Results: Baseline GlycoCirrhoTest values were significantly increased in patients who developed hepatocellular carcinoma after a median follow-up of 6.4 years as compared with patients who did not. For patients with a baseline GlycoCirrhoTest exceeding 0.2, the HR for hepatocellular carcinoma development over the entire study (Cox regression) was 5.1 [95% confidence interval (CI), 2.2-11.7; P < 0.001], and the HR for hepatocellular carcinoma development within 7 years was 12.1 (95% CI, 2.8-51.6; P = 0.01) based on the cut-off value optimized in the same cohort. An absolute increase in GlycoCirrhoTest of 0.2 was associated with an HR of 10.29 (95% CI, 3.37-31.43; P < 0.001) for developing hepatocellular carcinoma. In comparison, the HR for the development of hepatocellular carcinoma within 7 years for AFP levels above the optimal cutoff in this study (5.75 ng/mL) was 4.65 (95% CI, 1.59-13.61).Conclusions: This prognostic study suggests that GlycoCirrhoTest is a serum biomarker that identifies compensated cirrhotic patients at risk for developing hepatocellular carcinoma. Screening strategies could be guided by a positive test on GlycoCirrhoTest. Clin Cancer Res; 23(11); 2750-8. ©2016 AACR.
Pramipexole vs Levodopa as initial treatment for Parkinson disease: A randomized controlled trial
Authors: R. Holloway, I. Shoulson, K. Kieburtz, M. McDermott, P. Tariot, C. Kamp, D. Day, A. Shinaman, S. Fahn, A. Lang, K. Marek, J. Seibyl, W. Weiner, M. Welsh, R. Pahwa, S. Coe, L. Barclay, L. Sutherland, K. Hildebrand, J. Hubble, C. Weeks, P. Lewitt, J. Miyasaki, J. Duff, E. Sime, O. Suchowersky, M. Stacy, M. Kurth, M. Brewer, M. Harrigan, D. S. Russell, B. Fussell, B. Ford, S. Dillon, J. Hammerstad, C. Stone, D. Riley, P. Rainey, D. Standaert, M. Tennis, F. Wooten, E. Rost-ruffner, S. Factor, D. Brown, J. Jankovic, F. Atassi, R. Kurlan, I. Gardiner, M. Panisset, D. Amyot, J. Hall, A. Rajput, T. Shirley, R. Rodnitzky, J. Dobson, C. Shults, D. Fontaine, C. Waters, S. Schuman, R. Pfeiffer, S. Rast, B. Pfeiffer, A. Brocht, C. Casaceli, S. Daigneault, K. Hodgeman, K. Honsinger, C. O'Connell, A. Watts
Journal: JAMA (2000)
Abstract 547: Diagnosis of lung tumor types based on metabolomic profiles in lymph node aspirates
Authors: Daniel R. Sappington, Scott A. Helms, Eric Siegel, Susanne K. Jeffus, Teka Bartter, Thaddeus Bartter, Gunnar Boysen
Journal: Cancer Research (2015)

Abstract Lung cancer is the leading cause of cancer-related deaths in the US and worldwide. The majority of lung cancer patients are diagnosed with an advanced stage, precluding curable surgical resection, and therapy is limited to thoracic radiation and chemotherapy. The efficacies have improved in recent years due to patient pre-selection based on the cytology of fine needle aspirates of lymph nodes, which harbor circulating tumor cells. We report herein the evaluation of lymph node aspirates for the presence of metabolite features that are suitable to distinguish patients with lung cancer from patients without malignancies and to separate patients with adenocarcinoma from patients with squamous cell carcinoma. The results provide evidence that patient groups can be separated based on their metabolite profiles. Multivariate statistical analyses (PLS and OPLS) produce a set of consensus features that can be further developed into clinical biomarkers. Two of the features were identified as kynurenine and oxidized glutathione, and their identities were confirmed in a second larger sample set. In addition, the accompanying metabolites glutamate, glutamine and tryptophan were included in the validation experiment to utilize relative metabolite ratios as indicators for corresponding enzyme activities. The validation results demonstrate significant differences in metabolites and metabolite ratios between lymph node aspirates harboring a circulating tumor cell and aspirates negative for malignancy. Subsequently, a second set of lymph node samples were analyzed for an extended panel of metabolites and of these 42 were suitable biomarker to be statistically significant to distinguish between at least one of the pair wise comparisons. Together the results demonstrate that metabolite profiles in lymph node aspirates are suitable to differentiate patients with adenocarcinoma from patients with squamous cell carcinoma. Citation Format: Daniel R. Sappington, Scott A. Helms, Eric Siegel, Susanne K. Jeffus, Teka Bartter, Thaddeus Bartter, Gunnar Boysen. Diagnosis of lung tumor types based on metabolomic profiles in lymph node aspirates. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 547. doi:10.1158/1538-7445.AM2015-547
Predictors of Clinical Response in Patients with High Risk Acute Myeloid Leukemia Receiving Treatment with the Histone Deacetylase Inhibitor Sodium Valproate.
Authors: Charles Craddock, Charlotte Bradbury, Sujaatha Narayanan, Adam Rye, Supratik Basu, Alan MacWhannell, Alistair Sawers, Mark Cook, Michael Griffiths, David Grimwade, Christopher Bunce, Bryan Turner
Journal: Blood (2005)
Ultra-Deep Sequencing of the Bcr-Abl Kinase Domain Allows Earlier Detection and More Accurate Characterization of Resistant Subclones in Philadelphia-Positive Acute Lymphoblastic Leukemia Patients Receiving Tyrosine Kinase Inhibitor-Based Therapies
Authors: Simona Soverini, Caterina De Benedittis, Katerina Machova Polakova, Adela Brouckova, Cristina Papayannidis, Paola Bresciani, Valeria Coluccio, Ilaria Iacobucci, Claudia Venturi, Mario Luppi, Emanuela Ottaviani, Federica Cattina, Robin Foà, Antonella Vitale, Domenico Russo, Michele Baccarani, Giovanni Martinelli
Journal: Blood (2012)
Abstract 1068: Correlation of DNA methylation pattern between peripheral blood cell and normal breast tissue
Authors: Xingyi Guo, Xiao-Ou Shu, Chun Li, Jirong Long, Bingshan Li, Yu-Tang Gao, Wei Zheng, Qiuyin Cai
Journal: Cancer Research (2015)

Abstract Aberrant DNA methylation in peripheral blood cells (PBCs) may be a potential noninvasive biomarker for breast cancer risk. Whether methylations at CpG sites in PBCs can serve as proxies in normal breast tissues are unknown. We evaluated the correlation of DNA methylation between PBC DNA and breast cancer adjacent normal tissue using data and samples from the Shanghai Breast Cancer Study. Genome-wide DNA methylation profiles in PBCs and matched tumor adjacent normal tissues from 31 breast cancer patients were assayed using Illumina HumanMethylation450 BeadChip, which includes &amp;gt;485,000 CpG sites and covers 99% of RefSeq genes with multiple probes per gene. After quality control filtering, a total of 432,513 CpG sites were retained for analysis. We evaluated the association of methylation for each CpG site between DNA samples for PBCs and normal breast tissue using Spearman's rank correlation (r). The overall median correlation (r) is 0.35. A total of 99,928 (23.1%) and 18,290 (4.2%) of CpG sites had a high correlation between PBC DNA and normal breast tissue DNA with r &amp;gt; 0.50 and r &amp;gt; 0.75, respectively. Interestingly, we found that the correlation was negatively associated with both methylation levels (mean) and inter-person variability (standard deviation) in normal breast tissues (ρ = -0.14 and -0.19; P &amp;lt; 2.2 x10-16 for both). In 926 previously reported methylation quantitative trait loci, the correlations between PBCs and normal breast tissue were significantly higher (median r = 0.42) than the remaining loci (median r = 0.34) (Wilcoxon test, P &amp;lt; 2.2 x10-16), suggesting that methylation variations controlled by genetic variations exhibited a robust correlation between PBC and normal breast tissue DNA. In summary, our results suggest that the methylation status of CpG sites with large inter-person variations or genetically-controlled variations in PBC DNA correlate well with those in normal breast tissue. This supports the conduct of a genome-wide methylation study for breast cancer using PBC DNA. Citation Format: Xingyi Guo, Xiao-Ou Shu, Chun Li, Jirong Long, Bingshan Li, Yu-Tang Gao, Wei Zheng, Qiuyin Cai. Correlation of DNA methylation pattern between peripheral blood cell and normal breast tissue. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1068. doi:10.1158/1538-7445.AM2015-1068
Retrospective Application of European LeukemiaNet Provisional Criteria for Second-Generation TKI Chronic Myeloid Leukemia
Authors: Massimo Breccia, Roberto Latagliata, Fabio Stagno, Antonella Gozzini, Elisabetta Abruzzese, Francesco Albano, Vincenzo Federico, Federica Sorà, Paolo Vigneri, Giuseppina Loglisci, Malgorzata Trawinska, Simona Sica, Giorgina Specchia, Valeria Santini, Giuliana Alimena
Journal: Blood (2010)
Abstract 1515: Inhibition of the IKK/NF-κB pathway impairs glioma stem cell function
Authors: Amanda L. Rinkenbaugh, Patricia C. Cogswell, Albert S. Baldwin
Journal: Cancer Research (2015)

Abstract Glioma, the most frequently occurring primary brain tumor, has a median survival of less than 15 months, despite multimodal treatment combining surgery, radiation, and chemotherapy. It has been suggested that the presence of cancer stem cells (CSCs) within these tumors are responsible for resistance to treatment and high probability of recurrence. As a result, there is increasing interest in specifically targeting CSCs with new therapies to improve treatment of this disease. NF-κB has been implicated in numerous forms of cancer, as its target genes regulate hallmarks of cancer such as cell proliferation, survival, and invasion. Both glioma cell lines and tumor samples show high levels of phosphorylated p65, a marker of NF-κB activation. When comparing populations from tumor explants, NF-κB is preferentially activated in the CSC subset. We are examining the effects of IKK/NF-κB inhibition on both heterogeneous glioma explants and purified (CD133+) CSCs from these explants. Inhibition of NF-κB through either genetic or pharmacological means abrogates neurosphere formation, an in vitro measure of stem cell function. Additionally, real-time PCR analysis indicates that inhibition of NF-κB leads to a decrease in target genes implicated in glioma CSC biology, such as A20 and IL-6. Through gene expression analysis, we have identified a set of NF-κB-dependent genes that potentially contribute to the CSC phenotype, including invasion. We are using ex vivo brain slices and in vivo xenograft models to examine our findings in a pre-clinical setting. Our studies indicate a significant role for the NF-κB pathway in the biology of glioma CSCs, with possible parallels in CSCs of other tumor types. Citation Format: Amanda L. Rinkenbaugh, Patricia C. Cogswell, Albert S. Baldwin. Inhibition of the IKK/NF-κB pathway impairs glioma stem cell function. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1515. doi:10.1158/1538-7445.AM2015-1515
Clinical Outcome of the Treatment of Adult Acute Lymphoblastic Leukemia (ALL) with the Hyper-CVAD Protocol.
Authors: Theodoros Marinakis, Athanasios Zomas, Athanasios G. Galanopoulos, Eurydiki Michalis, George Gortzolidis, Ioannis Tsourveloudis, Ioanna Savvidou, George Theodoropoulos, Stephanos Papadhimitriou, George Paterakis, Vasiliki Grigoraki, Maria Georgiakaki, Nikolaos I. Anagnostopoulos
Journal: Blood (2005)
Intestinal Helminth Colonization Regulates Lethal Graft Versus Host Disease and Preserves Graft Versus Tumor in Bone Marrow Transplanted Mice
Authors: Yue Li, Hung-lin Chen, Nadine Bannick, Michael D. Henry, David E. Elliott, George J Weiner, Bruce R. Blazar, M. Nedim Ince
Journal: Blood (2014)
Psychometric properties of the St George's Respiratory Questionnaire in patients with idiopathic pulmonary fibrosis
Authors: Jeffrey J. Swigris, Dirk Esser, Hilary Wilson, Craig S. Conoscenti, Hendrik Schmidt, Wibke Stansen, Nancy Kline Leidy, Kevin K. Brown
Journal: European Respiratory Journal (2016)

The St George's Respiratory Questionnaire (SGRQ) has been used to measure health-related quality of life (HRQoL) in patients with idiopathic pulmonary fibrosis (IPF). This analysis evaluated the psychometric properties of the SGRQ using data from 428 patients with IPF who participated in a 12-month, randomised, placebo-controlled phase II trial of nintedanib. Internal consistency (Cronbach's α) was 0.91 for SGRQ total and &gt;0.70 for domain scores. Test–retest reliability (intraclass correlation coefficients) was 0.77, 0.77, 0.69 and 0.66 for SGRQ total, activity, impact and symptoms scores, respectively. Construct validity of SGRQ total and domain scores was supported by weak to moderate cross-sectional correlations with the Medical Research Council dyspnoea scale (0.32–0.55), 6-min walk test distance (−0.25– −0.34), percentage predicted forced vital capacity (−0.11– −0.15) and measures of gas exchange (−0.26–0.03). There was some evidence that the SGRQ total score was sensitive to detecting change. The reliability, construct validity and responsiveness of the SGRQ in patients with IPF suggest that this is an acceptable measure of HRQoL in patients with IPF.
592. High Quality Grade Plasmid DNA for Indirect Clinical Applications
Authors: Marco Schmeer, Ram Shankar, Tatjana Buchholz, Martin Schleef
Journal: Molecular Therapy (2016)

Amongst other applications, our plasmid DNA is used in the GMP-compliant production of recombinant viruses, antibodies and RNA, where these are the active pharmaceutical ingredients (API) used in clinical trials. Here, it is not always necessary to produce the plasmid DNA under GMP as well, in order to use it for such applications. An alternative is the so-called High Quality Grade plasmid DNA which is highly purified and well-characterised and, hence, meeting the requirements of most regulating agencies. High Quality Grade plasmid DNA is produced in our facility based on a research cell bank (RCB) and the very effective, patented ccc Grade DNA technology. A number of quality controls, both to the cell bank and to the plasmid DNA product, ensure that the final result is a product designed especially for the intended application and that complies with the appropriate regulatory standards. PlasmidFactory's new facility for the production of this high purity plasmid DNA is now operating successfully in new, modern labs where plasmid DNA of the highest quality is being produced in accordance with the EMEA guideline CHMP/BWP/2458/03. To ensure product safety, substances of animal origin are not used at any stage of the entire process, guaranteeing maximum possible product purity by reliable exclusion of contaminants such as bacterial chromosomal DNA or damaged plasmids. Only one plasmid is produced in each area - different plasmids are not produced in parallel in the same lab.
Short-Term Foamyviral Transduction with Virions Encoding Recombinant Corrects the Mitomycin C Hypersensitivity of Fancc −/− Progenitor Cells In Vitro and Restores Long Term Repopulating Activity of Fancc −/− Stem Cells In Vivo.
Authors: Yue Si, Cordula Leurs, Edward Srour, Samantha Ciccone, Helmut Hanenberg, D. Wade Clapp
Journal: Blood (2004)