tbuckley/cabot-search huggingface dataset:
Abstract LB-362: A six-gene classifier stratifies low-grade glioma patients with wild-type IDH
Authors: Alexander Huebner, Oliver Oehlke, Tareq A. Juratli, Wei Meng, Ahmed Ibrahim, Bin Li, Daniel Erny, Pierre Robe, Dietmar Krex, Gabriele Schackert, Marco Prinz, Anca Grosu, Arnab Chakravarti
Journal: Cancer Research (2016)

Abstract Gliomas are the most common primary brain tumors presenting a heterogeneous group of malignancies. Particularly, there is a significant heterogeneity in outcomes of patients with grade II and grade III gliomas. There has been recent progress in reclassifying glomas by integrating molecular signatures such as IDH mutation status, 1p/19q co-deletion and alternative telomer maintenance to the established histopathological classification scheme. Patients with IDH wild-type (WT) gliomas are found to have the worst prognosis. Currently there is no prognostic or predictive biomarker within this group of patients. To this end, the goal of the current study was to develop a gene classifier for identifying a prognostic/predictive biomarker model for grade II and grade III gliomas with IDH WT, which would have the potential of identifying patient groups with distinct degrees of risk for disease progression, treatment options, and survival outcome. Our approach was to identify a robust list of candidate genes using multiple datasets and create a single score classifier based on the expression of identified genes. We analyzed multiple datasets comprising a total of 756 glioma patients using a meta-analysis approach which identified six prognostic genes. A linear model consisting of these six genes was trained in an institutional cohort by employing RNAseq and qRT-PCR techniques to measure the gene expression and validated in an independent grade II/III glioma set (TCGA LGG). The classifier performed significantly in both the institutional cohort of 85 grade II/III glioma patients (HR, 29.94; 95% CI, 3.96-226.36; p = 0.001) and in the TCGA LGG dataset consisting of 416 glioma patients (HR, 4.03; 95% CI, 1.82-8.92; p = 0.001, for low versus high risk group). Multivariate Cox regression analysis validated the risk classifier independent of other clinical factors. After analyzing patient populations separately, based on IDH mutation status, we discovered that the classifier performed with high significance in the patients with IDH WT both in the institutional cohort and the TCGA LGG dataset (HR, 1.93; 95% CI, 1.24-3.02; p = 0.004 and HR, 1.99; 95% CI, 1.38-2.87; p &amp;lt; 0.001 respectively) reliably predicting the clinical outcomes. Citation Format: Alexander Huebner, Oliver Oehlke, Tareq A. Juratli, Wei Meng, Ahmed Ibrahim, Bin Li, Daniel Erny, Pierre Robe, Dietmar Krex, Gabriele Schackert, Marco Prinz, Anca Grosu, Arnab Chakravarti. A six-gene classifier stratifies low-grade glioma patients with wild-type IDH. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-362.
Incidence, Predictors, and Outcomes of New-Onset Atrial Fibrillation in Critically Ill Patients with Sepsis. A Cohort Study
Authors: Peter M. C. Klein Klouwenberg, Jos F. Frencken, Sanne Kuipers, David S. Y. Ong, Linda M. Peelen, Lonneke A. van Vught, Marcus J. Schultz, Tom van der Poll, Marc J. Bonten, Olaf L. Cremer
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Rationale: Patients admitted to intensive care units with sepsis are prone to developing cardiac dysrhythmias, most commonly atrial fibrillation.Objectives: To determine the incidence, risk factors, and outcomes of atrial fibrillation in a cohort of critically ill patients with sepsis.Methods: We assessed the association between atrial fibrillation and mortality using time-dependent competing risks survival analysis. Subsequently, for development of a risk score estimating the probability of a first occurrence of atrial fibrillation within the following 24 hours, we performed logistic regression analysis.Measurements and Main Results: Among 1,782 patients with sepsis admitted to two tertiary intensive care units in the Netherlands between January 2011 and June 2013, a total of 1,087 episodes of atrial fibrillation occurred in 418 (23%) individuals. The cumulative risk of new-onset atrial fibrillation was 10% (95% confidence interval [CI], 8–12), 22% (95% CI, 18–25), and 40% (95% CI, 36–44) in patients with sepsis, severe sepsis, and septic shock, respectively. New-onset atrial fibrillation was associated with a longer stay (hazard ratio [HR], 0.55; 95% CI, 0.48–0.64), an increased death rate (HR, 1.52; 95% CI, 1.16–2.00), and an overall increased mortality risk (subdistribution HR, 2.10; 95% CI, 1.61–2.73) when considering discharge as a competing event. A simple risk score for daily prediction of atrial fibrillation occurrence yielded good discrimination (C statistic, 0.81; 95% CI, 0.79–0.84) and calibration (chi-square, 9.38; P = 0.31), with similar performance in an independent validation cohort (C statistic, 0.80; 95% CI, 0.76–0.85).Conclusions: Atrial fibrillation is a common complication of sepsis and independently associated with excess mortality. A simple risk score may identify patients at high risk of this complication.Clinical trial registered with www.clinicaltrials.gov (NCT 01905033).
Expression Level Of A Coagulation Factor Gene, F13A1 Defines Characteristic Subpopulations Of Childhood Acute Lymphoblastic Leukemia
Authors: Csongor Kiss, Katalin Gyurina, Gábor Kiss, Silvia Bresolin, Zsuzsa Hevessy, Imre Gáspár, István Szegedi, János Kappelmayer, te Kronnie Geertruy, Beáta Scholtz, Giuseppe Basso
Journal: Blood (2013)
Microalbuminuria Is Associated with An Increased Risk of Venous Thromboembolism. A Novel Risk Marker for Venous Thromboembolism
Authors: Bakhtawar Khan Mahmoodi, Ron T. Gansevoor, Nic J.G.M. Veeger, Hans L. Hillege, Gerjan Navis, Jan van der Meer
Journal: Blood (2008)
Abstract 1948: MiRNA profiling of dogs with transitional cell carcinoma of the bladder using blood and urine samples
Authors: Michael Kent, Allison Zwingenberger, Jodi Westropp, Laura Barrett, Paramita Ghosh, Ruth L. Vinall
Journal: Cancer Research (2016)

Abstract Early symptoms of canine transitional cell carcinoma (TCC) are frequently assumed to be caused by other lower urinary tract diseases (LUTD) such as urinary tract infections, resulting in late diagnosis of TCC and decreased rates of survival. To determine whether miRNA can be used as non-invasive diagnostic biomarkers in this setting, we assessed miRNA expression in RNA extracted from urine and blood from dogs with clinically normal bladders (n = 28), LUTD (n = 25), and TCC (n = 18). Expression levels of 5 miRNA associated with TCC pathophysiology (miR-34a, let-7c, miR-16, miR-103, and miR-106b) were assessed by quantitative real-time PCR. Statistical analyses using ranked ANOVA identified significant differences in miR-103 and miR-16 levels between urine samples from LUTD and TCC patients (miR-103, fold change = 2.55, p = 0.015; and miR-16, fold change = 3.02, p = 0.002). However, logistic regression analyses determined miR-103, but not miR-16, can distinguish between canine LUTD and TCC patients (OR = 0.78 p = 0.031, AUC = 0.85). No statistically significant differences in miRNA levels were observed between blood samples from LUTD versus TCC patients. Expression levels of miR-34a trended with miR-16, let-7c, and miR-103 levels in normal urine samples, however, this coordination was completely lost in TCC urine samples. In contrast, cooordination of miR-34a, miR-16, let-7c, and miR-103 expression levels was maintained in blood samples from TCC patients. Our combined data indicate further investigation of miR-103 as a diagnostic urine biomarker for TCC, and investigation of the role of miR-103 as well as dysregulation of coordinated miRNA expression in bladder carcinogenesis, is warranted. Citation Format: Michael Kent, Allison Zwingenberger, Jodi Westropp, Laura Barrett, Paramita Ghosh, Ruth L. Vinall. MiRNA profiling of dogs with transitional cell carcinoma of the bladder using blood and urine samples. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1948.
Abstract 5142: Correlation of peripheral blood S100A9+ myeloid-derived suppressor cells and tumor-associated macrophages in lung adenocarcinoma patient
Authors: Kang-Yun Lee, Po-Hao Feng
Journal: Cancer Research (2016)

Abstract Background: Peripheral blood S100A9+ monocytic myeloid derived suppressor cells (MDSCs) is a predictive factor for treatment response of chemotherapy and epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) of lung adenocarcinoma patients. Tumor associated macrophages (TAMs), which might derived from peripheral blood monocyte, is also a predictive factor to treatment response of EGFR-TKI. However, the correlation of S100A9+ monocytic MDSCs and TAMs is not well understood in lung adenocarcinoma patients. Methods: Stage IV lung adenocarcinoma patients with paired formalin fixed paraffin embedded (FFPE) tumor tissue and peripheral blood mononuclear cell (PBMCs) were enrolled. CD68+ cells were calculated in 3 different 200X microscopic field of FFPE as TAMs, and S100A9+ cells also calculated with same method as MDSCs in tumor microenvironment. S100A9+ MDSCs percentage was calculated by flow cytometry from CD14+S100A9+ in PBMC. Results: Twenty-four lung adenocarcinoma patients with paired FFPE tissue and PBMC data were enrolled. PBMC S100A9+ MDSCs percentage is 17.9± 13.6; average number of S100A9+ cells and CD68+ TAMs in tumor tissue is 96.8±45.7 and 79.3±13.3, respectively. The correlation between S100A9+ MDSCs percentage and tissue S100A9+ cells and CD68+ TAMs is significant (Spearman r = 0.54, p = 0.003 for S100A9+; Spearman r = 0.03, p = 0.03 for CD68; n = 24) CD68+ and S100A9+ cells were also correlated (Spearman r = 0.41, p = 0.04, n = 24). Clinically, high or low (cutoff value as median number) tissue S100A9+ cells and CD68+ TAMs were both predictive factors for treatment PFS for EGFR-TKI. (For CD68, median: 56, high vs low TAM PFS = 7.4 vs 15.4 months, p = 0.04; For S100A9+ cells, median: 76, high vs low S100A9+ cells PFS = 7.2 vs 13.6 months, p = 0.05) Conclusion: Peripheral blood S100A9+ MDSCs is well correlated to tumor tissue S100A9+ cells and CD68+ TAMs. Both tissue S100A9+ cells and CD68+ TAMs were predictive factors for EGFR-TKI PFS. Our study suggests that peripheral blood S100A9+ monocytic MDSC might be one of the origin of tumor tissue CD68+ TAMs. Citation Format: Kang-Yun Lee, Po-Hao Feng. Correlation of peripheral blood S100A9+ myeloid-derived suppressor cells and tumor-associated macrophages in lung adenocarcinoma patient. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5142.
Evaluating Acetate Metabolism for Imaging and Targeting in Multiple Myeloma
Authors: Francesca Fontana, Xia Ge, Xinming Su, Deep Hathi, Jingyu Xiang, Simone Cenci, Roberto Civitelli, Kooresh I. Shoghi, Walter J. Akers, Andre D'avignon, Katherine N. Weilbaecher, Monica Shokeen
Journal: Clinical Cancer Research (2016)

We hypothesized that in multiple myeloma cells (MMC), high membrane biosynthesis will induce acetate uptake in vitro and in vivo Here, we studied acetate metabolism and targeting in MMC in vitro and tested the efficacy of 11C-acetate-positron emission tomography (PET) to detect and quantitatively image myeloma treatment response in vivo EXPERIMENTAL DESIGN: Acetate fate tracking using 13C-edited-1H NMR (nuclear magnetic resonance) was performed to study in vitro acetate uptake and metabolism in MMC. Effects of pharmacological modulation of acetate transport or acetate incorporation into lipids on MMC cell survival and viability were assessed. Preclinical mouse MM models of subcutaneous and bone tumors were evaluated using 11C-acetate-PET/CT imaging and tissue biodistribution.In vitro, NMR showed significant uptake of acetate by MMC and acetate incorporation into intracellular metabolites and membrane lipids. Inhibition of lipid synthesis and acetate transport was toxic to MMC, while sparing resident bone cells or normal B cells. In vivo, 11C-acetate uptake by PET imaging was significantly enhanced in subcutaneous and bone MMC tumors compared with unaffected bone or muscle tissue. Likewise, 11C-acetate uptake was significantly reduced in MM tumors after treatment.Uptake of acetate from the extracellular environment was enhanced in MMC and was critical to cellular viability. 11C-Acetate-PET detected the presence of myeloma cells in vivo, including uptake in intramedullary bone disease. 11C-Acetate-PET also detected response to therapy in vivo Our data suggested that acetate metabolism and incorporation into lipids was crucial to MM cell biology and that 11C-acetate-PET is a promising imaging modality for MM. Clin Cancer Res; 23(2); 416-29. ©2016 AACR.
Abstract 3096: Mapping lysine acetyltransferase-metabolite interactions in complex proteomes: a window into the metabolic regulation of epigenetic signaling
Authors: Jordan L. Meier
Journal: Cancer Research (2016)

Abstract Substantial evidence indicates that chromatin modifiers are sensitive to changes in the cellular concentration of metabolites and cofactors. These findings potentially connect metabolism and gene expression, and have major implications for the regulation of cell signaling in cancer. However, missing from many of these studies has been the direct identification of the specific chromatin modifiers that sense change in metabolic state. Their identification is critical to our basic understanding of how metabolism regulates epigenetically-driven phenotypes, and may inform novel strategies to combat pathologies characterized by aberrant metabolism, including cancer. Towards this goal, here we report a chemical proteomic strategy to globally map chromatin modifier-metabolite interactions in complex proteomes. Our initial efforts have focused on lysine acetyltransferases (KATs), a central class of chromatin modifiers responsible for histone acetylation. First, we validate an optimized chemical proteomic method and demonstrate its ability to globally profile members of the KAT enzyme superfamily at endogenous expression levels. Then we apply this approach to rapidly profile KAT-ligand interactions, and identify novel candidate metabolic regulators of protein acetylation, including acyl-CoAs cofactors and metabolites, as well as new metabolically-sensitive KAT enzymes. By defining the molecular interactions linking metabolism and gene expression, these studies have the potential to illuminate our understanding of biology and inspire new therapeutic strategies targeting acetylation in disease. Citation Format: Jordan L. Meier. Mapping lysine acetyltransferase-metabolite interactions in complex proteomes: a window into the metabolic regulation of epigenetic signaling. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3096.
Case 22-1979
Authors: Richard C. Cabot, Robert E. Scully, James J. Galdabini, Betty U. McNeely, Robert W. Bunting, Steven C. Quay
Journal: New England Journal of Medicine (1979)

Presentation of CaseA 38-year-old man was admitted to the hospital because of fever.The patient had a long history of chronic glomerulonephritis with renal failure. Eight years before admission he underwent bilateral nephrectomy and received a left renal transplant from a sister. Microscopical examination of the kidneys showed severe chronic glomerulonephritis. Listeria meningitis developed postoperatively. Shortly thereafter aseptic necrosis of the hips occurred, and bilateral total hip replacement was performed. Eight months after the transplant the dose of prednisone was increased because of an interstitial renal rejection reaction. Methyldopa and chlorothiazide were prescribed for mild hypertension. X-ray films of . . .
Abstract 499: ESR1 methylation in circulating tumor cells of patients with breast cancer
Authors: Sofia Mastoraki, Areti Strati, Maria Chimonidou, Nikos S. Malamos, Vasilis Georgoulias, Evi S. Lianidou
Journal: Cancer Research (2016)

Abstract AIMS: DNA methylation is an epigenetic alteration which plays a decisive role in the regulation of signal translation processes. In our lab, we have demonstrated for the first time the epigenetic silencing of tumor and metastasis suppressor genes in CTCs through their promoter methylation. Estrogen receptor (ER) is an important prognostic biomarker and is predictive of response to endocrine therapy in breast cancer. In this study, we evaluated for the first time ESR1 methylation in CTCs of breast cancer patients. METHODS: We developed and validated a novel highly sensitive and specific qMSP assay for ESR1 methylation using commercially available DNA methylation controls and the MDA-MB-231 cell line. We further examined its performance in EpCAM-positive immune-magnetically isolated CTC fractions, followed by DNA isolation and sodium bisulfite (SB) treatment from: a) 74 operable, b) 48 metastasis- verified breast cancer patients and c) 30 healthy donors (control group). RESULTS: The developed assay is highly specific and sensitive since it can detect 0.1% methylated ESR1 sequences in the presence of 99.9% un-methylated. ESR1 was found to be methylated in 16/74 (21.6%) operable breast cancer patients, in 10/48 (20.8%) patients with verified metastasis, but only in 1/30 (3.3%) healthy donors (EpCAM-positive CTC fraction). CONCLUSIONS: The EpCAM-positive CTC fraction was found to be methylated for ESR1 in about 20% of patients with breast cancer. We will further evaluate these findings in respect to the clinical outcome of these patients, since the epigenetic silencing of ESR1 could be of important clinical significance especially for its impact on the efficacy of treatment. Citation Format: Sofia Mastoraki, Areti Strati, Maria Chimonidou, Nikos S. Malamos, Vasilis Georgoulias, Evi S. Lianidou. ESR1 methylation in circulating tumor cells of patients with breast cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 499.
Abstract 1615: Low Frequency Of Detection Of Viral Genomes In Endomyocardial Biopsies From Patients With Dilated Cardiomyopathy
Authors: Silvia Moimas, Serena Zacchigna, Marco Merlo, Andrea Di Lenarda, Gianfranco Sinagra, Mauro Giacca
Journal: Circulation (2007)

Over the last several years, a number of studies have suggested the possibility that dilated cardiomyopathy (DCM) might ensue as the sequelae of myocarditis of viral etiology, with particular refer...
Blockade of interleukin-27 signaling reduces GVHD in mice by augmenting Treg reconstitution and stabilizing Foxp3 expression
Authors: Ludovic Belle, Kimberle Agle, Vivian Zhou, Cheng Yin-Yuan, Richard Komorowski, Daniel Eastwood, Brent Logan, Jie Sun, Nico Ghilardi, Daniel Cua, Calvin B. Williams, Melanie Gaignage, Reece Marillier, Jacques van Snick, William R. Drobyski
Journal: Blood (2016)
The Clinical Impact of Thalidomide Maintenance on Progression Free Survival and Postrelapse Survival after Autologous Stem Cell Transplantation in Patients with Newly Diagnosed Multiple myeloma
Authors: Ho Sup Lee, Yang Soo Kim, Chang-Ki Min, Je-Jung Lee, Kihyun Kim, Dok Hyun Yoon, Hyeon Seok Eom, Hyewon Lee, Won Sik Lee, Ho-Jin Shin, Ji Hyun Lee, Yong Park, Jae-Cheol Jo, Young Rok Do, Yeung-Chul Mun
Journal: Blood (2014)
PTPN22 inhibition resets defective human central B cell tolerance
Authors: Jean-Nicolas Schickel, Marcel Kuhny, Alessia Baldo, Jason M. Bannock, Christopher Massad, Haowei Wang, Nathan Katz, Tyler Oe, Laurence Menard, Pauline Soulas-Sprauel, Till Strowig, Richard Flavell, Eric Meffre
Journal: Science Immunology (2016)

The 1858T protein tyrosine phosphatase nonreceptor type 22 (PTPN22 T) allele is one of the main risk factors associated with many autoimmune diseases and correlates with a defective removal of developing autoreactive B cells in humans. To determine whether inhibiting PTPN22 favors the elimination of autoreactive B cells, we first demonstrated that the PTPN22 T allele interfered with the establishment of central B cell tolerance using NOD-scid-common γ chain knockout (NSG) mice engrafted with human hematopoietic stem cells expressing this allele. In contrast, the inhibition of either PTPN22 enzymatic activity or its expression by RNA interference restored defective central B cell tolerance in this model. Thus, PTPN22 blockade may represent a therapeutic strategy for the prevention or treatment of autoimmunity.
Abstract 306: Analysis of differentially expressed exosomal genes from ibrutinib resistant diffuse large B cell lymphoma
Authors: Neeraj Jain, Lalit Sehgal, Tamer Khashab, Felipe Samaniego
Journal: Cancer Research (2016)

Abstract Diffuse large B cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma (NHL) and approximately 30% of the patients develop relapsed/refractory disease that becomes a major cause of mortality and morbidity. Selective pressure provided by chemotherapy causes aberrant gene expression and selection of pre-existing population of chemo-resistant cells. These chemo-resistant cells can also transmit chemo-resistance to chemo-sensitive cells through exosomal transfer of molecules (miRNA, mRNA and proteins). In this study, we have analysed differentially expressed mRNA and miRNA from syngeneic ibrutinib (an irreversible BTK inhibitor, FDA approved) resistant DLBCL cells and from their isolated exosomes. Five DLBCL-GCB and five ABC subtype were analysed for their sensitivity with ibrutinib. We found three ABC subtype and one GCB subtype (OCL-LY1) were sensitive to ibrutinib. We have generated syngeneic ibrutinib drug resistant model from sensitive cells (at least 10 fold increase in IC50 value) by continuous culturing them in the presence of ibrutinib with gradual increase in drug concentration in each passage. Ibrutinib sensitive DLBCL cells when cultured with the syngeneic resistant cells in transwell apparatus, acquired resistance to ibrutinib. We also analysed the sensitivity of ibrutinib resistant cells with other conventional drugs for non-Hodgkin lymphomas. We further tested the expression of drug resistant genes in syngeneic resistant cells by real time PCR analysis. Later, we isolated the total RNA and miRNA species from DLBCL ibrutinib sensitive, their syngeneic resistant cells and from respective exosomes and analysed for differential expression by micro array analyses. Thus in conclusion, our study demonstrates that chemo-resistance can be transferred from resistant cells to sensitive cells via exosomal horizontal transmission of miRNA and mRNA in diffuse large B cell lymphoma cells. Moreover, our study identified potential targets that can be used to overcome chemo-resistance in diffuse large B cell lymphoma. Citation Format: Neeraj Jain, Lalit Sehgal, Tamer Khashab, Felipe Samaniego. Analysis of differentially expressed exosomal genes from ibrutinib resistant diffuse large B cell lymphoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 306.