tbuckley/cabot-search huggingface dataset:
Abstract 995: The functional involvement of H19, a Long noncoding RNA, in human colorectal cancer
Authors: HUI LING, Masahisa Ohtsuka, Martin Pichler, Cristina Ivan, Daisuke Matsushita, George Calin
Journal: Cancer Research (2016)

Abstract The clinical significance of long noncoding RNAs (lncRNAs), defined as transcripts longer than 200 bp that do not code for proteins, in colorectal cancer (CRC) remains largely uncharacterized. We selected 10 lncRNAs associated with CRC, analyzed their expression association with patient survival using The Cancer Genome Atlas (TCGA) CRC data, and identified H19 as the one significantly associated with CRC patient survival. Experimental data using CRC cell line models showed that downregulation of H19 significantly reduced cancer cell proliferation, anchorage-independent growth, and cell migration capacity. Flow cytometric analysis suggested a clear G1 arrest of CRC cells following depletion of H19 expression. Our mechanism study suggests that H19 is pivotal in maintaining Wnt signaling and notch signaling. These finding represent a novel mechanism of H19 function in colorectal cancer, and strongly support the translational importance of this lncRNA as cancer marker and therapeutic target. Citation Format: HUI LING, Masahisa Ohtsuka, Martin Pichler, Cristina Ivan, Daisuke Matsushita, George Calin. The functional involvement of H19, a Long noncoding RNA, in human colorectal 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 995.
Abstract 973: A long noncoding RNA-regulating enhancer links Ewing sarcoma susceptibility to stress response
Authors: Dave NT Aryee, Eleni Tomazou, Maximilian Kauer, Thomas Grünewald, Franck Tirode, Olivier Delattre, Heinrich Kovar
Journal: Cancer Research (2016)

Abstract Ewing sarcoma is the second most frequent bone cancer in Caucasian children and young adults, but hardly occurs in Africans. It is characterized by a relatively quiet genome with only one highly recurrent chromosomal aberration, a EWS-ETS (predominantly EWS-FLI1) gene rearrangement. The resulting fusion gene encodes for an aberrant ETS transcription factor which drives sarcomagenesis. In a large GWAS study, three Ewing sarcoma susceptibility loci were discovered on chromosomes 1, 10 and 15, but the molecular mechanisms, how these loci affect tumorigenesis, remained largely unknown. By epigenomic mapping, EWS-FLI1 ChIP-seq, and reporter gene assays we found one of the susceptibility loci to localize to an EWS-FLI1 bound enhancer in the intron of a long non-coding antisense RNA, which we termed lncESST1 (Ewing Sarcoma Susceptibility Transcript 1). Deletion of the ETS binding region in the enhancer by CRISPR/Cas9 mediated gene editing lead to a drastic decrease in lncESST1 expression. Modulation of lncESST expression by siRNA or enhancer deletion significantly reduced soft agar colony formation of Ewing sarcoma cells without affecting growth under adherent culture conditions. Detachment of Ewing sarcoma cells from the plastic surface and growth under spheroid culture conditions induced stress granule formation as an immediate response, and a steady increase in lncESST1 expression over a period of at least 72 hours. We report that lncESST1 binds to a stress granule component with which it shares the promoter, and that loss of lncESST1 expression due to enhancer deletion perturbs stress granule formation. Our study therefore unveils a novel mechanism of lncRNA mediated cancer susceptibility. Supported by FWF grant I1225-B19 Citation Format: Dave NT Aryee, Eleni Tomazou, Maximilian Kauer, Thomas Grünewald, Franck Tirode, Olivier Delattre, Heinrich Kovar. A long noncoding RNA-regulating enhancer links Ewing sarcoma susceptibility to stress response. [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 973.
Abstract 3543: Alternating electric fields (TTFields) induce autophagy in human cancer cell lines
Authors: Yaara Porat, Anna Shteingauz, Moshe Giladi, Rosa S. Schneiderman, Tali Voloshin, Mijal Munster, Roni Blat, Eilon D. Kirson, Uri Weinberg, Yoram Palti
Journal: Cancer Research (2016)

Abstract Tumor treating fields (TTFields) are an established anti-neoplastic treatment modality in patients with glioblastoma. TTFields are delivered via noninvasive application of low-intensity, intermediate-frequency, alternating electric fields to the region of the tumor. Previous studies have shown that TTFields lead to increased granularity in treated cells. Granular or vesicular structures can indicate the formation of autophagosomes which are key structures in autophagy. Autophagy has been shown to regulate cell survival and proliferation under stress conditions and, in certain cases, influence cellular response to cytotoxic drugs. The goal of this study was to evaluate the possible effect of TTFields on the induction of autophapgy in treated cells. Different cancerous cell lines were treated with TTFields using the inovitro system. Cellular granularity was evaluated using flow cytometry. Autophagy was monitored by quantifying Lipidated Microtubule Associated Protein Light Chain 3 (LC3-II, a consensus marker for autophagosomes) levels using immunoblotting and immunofluorescence microscopy. Transmission Electron Microscopy (TEM) was used to visualize autophagosome-like structures. Flow cytometry analysis demonstrated that TTFields application leads to a significant increase in cellular granularity in all tested cell lines (up to 40%, P&amp;lt;0.05). Significant elevation in LC3-II levels was observed in treated U-87 MG cells using immunoblotting analysis (37%, P = 0.01). Evidence of increased autophagy following TTFields application was also detected using fluorescence microscopy, where punctate distribution of LC3-II was observed. TEM micrographs demonstrated the presence of autophagy typical, autophagosome-like structures in TTFields treated cells. TTFields are known to exert anti-mitotic effects by disrupting highly dipolar structures which play critical roles in mitosis. Our results suggest that in addition, TTFields can also induce cellular autophagy. Future studies are warranted to examine to what extent TTFields-elicited- autophagy may affect treatment outcomes, and to investigate the therapeutic implications of combining TTFields with autophagy inhibitors. Citation Format: Yaara Porat, Anna Shteingauz, Moshe Giladi, Rosa S. Schneiderman, Tali Voloshin, Mijal Munster, Roni Blat, Eilon D. Kirson, Uri Weinberg, Yoram Palti. Alternating electric fields (TTFields) induce autophagy in human cancer cell lines. [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 3543.
Hospital size and demographics associated with HCAHPS and implications for hospital value-based purchasing (HVBP).
Authors: Daniel Curtis McFarland, Katherine Ornstein, Randall F. Holcombe
Journal: Journal of Clinical Oncology (2014)

38 Background: Hospital Consumer Assessments of Healthcare Providers and Systems (HCAHPS) scores appear to be lower in densely populated areas and for urban academic medical centers (AMC). These patient satisfaction scores contribute to CMS reimbursement. We hypothesized that demographics and hospital factors such as size were significant determinants of HCAHPS. Methods: HCAHPS, hospital bed, and county demographics were obtained from the Hospital Compare, American Hospital Directory, and US Census Bureau websites, respectively. An aggregate positive score was created for each hospital. Multivariate regression modeling was performed for the aggregate positive score and all ten dimensions of HCAHPS. Standardized partial regression coefficients were used to assess strengths of postulated predictors (Table). A predictive formula based on the 4 strongest predictors was developed. An adjustment model corrected for demographic and hospital factors. Hospitals were rescored using this model to generate an adjusted score (WIPSAS – weighted individual patient satisfaction score). HCAHPS hospital ranking was compared to WIPSAS ranking for all NY State hospitals. HCAHPS were obtained from 3,192 hospitals and demographic data collected from 3,144 counties. Results: ‘Hospital beds’ and ‘non-English speaking’ were the strongest negative predictors while ‘% Bachelor’s’ and ‘white alone’ were the strongest positive predictors of HCAHPS. The adjusted r 2 was.22 for the model and.155 for the predictive formula. WIPSAS altered the ranking in NY State. The adjusted ranking moved 3 AMCs into the top ten (prior #42, #43, #46). Conclusions: Demographic and hospital factors influence HCAHPS. Adjusted scores may be more representative of a hospital’s actual performance. CMS should utilize WIPSAS adjusted scores in order to more fairly calculate HVBP reimbursements. [Table: see text]
Abstract 3283: APRIL/BCMA activation promotes human multiple myeloma progression and further induces immunosuppressive bone marrow microenvironment
Authors: Yu-Tzu Tai, Chirag Acharya, Gang An, Michele Moschetta, Mike Y. Zhong, Xiaoyan Feng, Michele Cea, Antonia Cagnetta, Kenneth Wen, Hans van Eenennaam, Andrea van Elsas, Nikhil Munshi, Kenneth Anderson
Journal: Cancer Research (2016)

Abstract Elevated B cell maturation antigen (BCMA) and its ligand a proliferation-inducing ligand (APRIL) may directly advance human multiple myeloma (MM) malignancy in vivo. Here, we first show that BCMA downregulation potently diminishes viability and colony formation of MM cells while BCMA overexpression augments MM cell growth and survival via induction of AKT, MAPK, and NFκB signaling cascades and molecules essential for proliferation and anti-apoptosis. Importantly, BCMA itself forces accelerated tumor growth of xenografted MM cells harboring p53 mutation in mice. BCMA-overexpressing tumors exhibit significantly enhanced CD31/microvessel density and VEGF than paired control tumors. Concurrently, these tumors express increased factors crucial for osteoclast activation, adhesion, and angiogenesis/metastasis, as well as immune inhibition including PD-L1, TGFβ and IL-10 which further triggers 38 IL-10 signaling molecules. In parallel, these identified target genes are induced by paracrine APRIL binding to BCMA in MM cells and they are potently blocked by an antagonistic anti-APRIL monoclonal antibody hAPRIL01A (01A). 01A is cytotoxic against MM cells protected by abnormal bone marrow (BM) myeloid cells, i.e., osteoclasts, macrophages, and plasmacytoid dendritic cells. It further decreases APRIL-induced adhesion and migration of MM cells via blockade of canonical and non-canonical NFκB pathways. It prevents in vivo MM cell growth within implanted human bone chips in SCID mice. 01A-inhibited MM cell viability induced by osteoclasts is further enhanced by lenalidomide and bortezomib. Taken together, these results further characterize new molecular mechanisms of APRIL/BCMA-induced in vivo MM progression and immunosuppressive BM microenvironment, strongly supporting targeting this prominent pathway in MM. Citation Format: Yu-Tzu Tai, Chirag Acharya, Gang An, Michele Moschetta, Mike Y. Zhong, Xiaoyan Feng, Michele Cea, Antonia Cagnetta, Kenneth Wen, Hans van Eenennaam, Andrea van Elsas, Nikhil Munshi, Kenneth Anderson. APRIL/BCMA activation promotes human multiple myeloma progression and further induces immunosuppressive bone marrow microenvironment. [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 3283.
The cross-talk between renal function, inflammation and psoriasis vulgaris
Authors: S. Coimbra, H. Oliveira, P. Rocha-Pereira, A. Figueiredo, A. Santos-Silva
Journal: British Journal of Dermatology (2016)

It has been reported that moderate-to-severe psoriasis present an increased risk for CKD, that is independent of traditional risk factors 2,3; and severe psoriasis was proposed as a risk factor for CKD and end-stage CKD 4. Psoriasis may induce kidney dysfunction through immune-mediated renal damage, and through psoriasis treatment, with drugs presenting nephrotoxicity, such as cyclosporine and methotrexate 5. Nonetheless, the exact mechanism(s) underlying the link between psoriasis and renal dysfunction remain unclear.

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Abstract 1890: IKBKE is a substrate of EGFR and a therapeutic target in NSCLCs with activating mutations of EGFR
Authors: Sridevi Challa, Jian-Ping Guo, Cheng-xiong Xu, Yajuan Li, Donghwa Kim, Douglas Cress, Eric Haura, Domenico Coppola, Jin Cheng
Journal: Cancer Research (2016)

Abstract EGFR is one of key driver pathways of non-small cell lung cancer (NSCLC). EGFR inhibitors have shown significant response in patients with EGFR mutation. However, patients develop resistance in short period of time, which results from secondary EGFRT790M mutation and other mechanisms. Here, we demonstrated that activating mutations of EGFR significantly activated IKBKE, an IκB kinase family member previously shown to activate Akt and NF-κB pathways. Furthermore, we showed that EGFR directly interacts with and phosphorylates IKBKE on tyrosine 153 and tyrosine 179 residues. IKBKE-Y153F/179-F, a mutant that could not be phosphorylated by EGFR, largely reduced its kinase activity and failed to activate Akt and NF-κB as well as inhibited EGFR signaling. Furthermore, phospho-IKBKE-Y153 correlated with EGFR activation in NSCLC patients. Notably, depletion of IKBKE by either small molecule inhibitor amlexanox or shRNA selectively inhibited cell viability in NSCLC cells with EGFR mutations. Moreover, we observed that inhibition of IKBKE led to feedback activation of the MAPK pathway. Combination of amlexanox with MEK inhibitor AZD6244 significantly inhibits cell survival and tumor growth in NSCLC cells driven by activating EGFR mutations including EGFRT790M. Thus, our findings not only identify IKBKE as a direct downstream target of EGFR but also provide a potential therapeutic strategy for EGFR-TKI resistant NSCLC driven by secondary EGFR mutation. Citation Format: Sridevi Challa, Jian-Ping Guo, Cheng-xiong Xu, Yajuan Li, Donghwa Kim, Douglas Cress, Eric Haura, Domenico Coppola, Jin Cheng. IKBKE is a substrate of EGFR and a therapeutic target in NSCLCs with activating mutations of EGFR. [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 1890.
Erratum: “An Integrated Experimental Design for the Assessment of Multiple Toxicological End Points in Rat Bioassays”
Authors: Fabiana Manservisi, Clara Babot Marquillas, Annalisa Buscaroli, James Huff, Michelina Lauriola, Daniele Mandrioli, Marco Manservigi, Simona Panzacchi, Ellen K. Silbergeld, Fiorella Belpoggi
Journal: Environmental Health Perspectives (2017)

[This corrects the article DOI: 10.1289/EHP419.].
Abstract 4719: Varlitinib demonstrates potent antitumor efficacy in patient-derived gastric cancer xenograft models
Authors: A. G. Lisa Ooi, Bertil E. Lindmark, Mark McHale, Huynh T. Hung, Richard Ong
Journal: Cancer Research (2016)

Abstract Varlitinib is a potent, reversible pan-HER inhibitor of the ATP-binding site of EGFR (IC50 = 7 nM), HER2 (IC50 = 2 nM) and HER4 (IC50 = 4 nM). Gastric Cancer is the fifth most common cancer worldwide, with 952,000 cases diagnosed in 2012, constituting 6.8% of total cancer diagnosis. Prognosis for gastric cancer is poor, with the overall 5-year survival rate for gastric cancer in the US at ∼29%. Current clinical guidelines recommend use of trastuzumab combined with chemotherapy for HER2+ (amplified) patients with advanced gastric cancer. However the majority of patients (∼80%) do not have HER2 amplification. Studies have implicated dysregulation of HER signaling in gastric cancer and there is strong scientific rationale for testing of pan-HER therapies in Gastric Cancer. We tested the anti-tumour activity of Varlitinib as a single agent in patient-derived gastric cancer xenograft in SCID mice (GC22-0808 &amp; GC11-0414) with over-expression of HER proteins. Varlitinib is very active in tumour growth inhibition studies, causing dose-dependent inhibition with tumour stasis observed at dosing of 50 mg/kg BID and tumour regression observed at dosing of 100 mg/kg BID. Tumour protein lysates after two-day treatment with Varlitinib and vehicle were also analysed to elucidate the mechanism of action. Multiple proliferation and anti-apoptosis pathways were inhibited by Varlitinib, including AKT, PI3K and Survivin pathways. In view of the robust anti-tumour activity inhibiting multiple survival and proliferation pathways, as well as the safe tolerabilty profile of Varlitinib, ASLAN has initiated Phase 2 clinical trials of Varlitinib in gastric cancer. Citation Format: A. G. Lisa Ooi, Bertil E. Lindmark, Mark McHale, Huynh T. Hung, Richard Ong. Varlitinib demonstrates potent antitumor efficacy in patient-derived gastric cancer xenograft models. [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 4719.
P0721 : Viral and host parameters in association with outcome of acute hepatitis C in HIV-coinfected patients
Authors: J. Dietz, T. Lutz, G. Knecht, P. Gute, C. Berkowski, C.M. Lange, P. Khaykin, C. Stephan, H.-R. Brodt, S. Zeuzem, C. Sarrazin
Journal: Journal of Hepatology (2015)
Retraction Note: TGFβ1 signaling via aVβ6 integrin
Authors: Martin P Kracklauer, Christian Schmidt, Guido M Sclabas
Journal: Molecular Cancer (2004)

The data published in this article [1] and in a subsequent article in Molecular Cancer [2] were generated by myself, the corresponding author, with collaborators in Germany. The data were originally part of a manuscript on which my collaborators were authors and which remains unpublished. When publishing the data in Molecular Cancer, I failed to obtain the agreement from my past collaborators or to acknowledge their contributions, resulting in an unfair representation of their ideas and thoughts. In light of this, I have decided to retract the two papers. I deeply apologize for any inconvenience this may have caused.
Eurosurveillance comes of age and moves to ECDC
Authors: H Therre, J  C Desenclos, E Hoile, N Gill, J B Brunet
Journal: Eurosurveillance (2007)

Eurosurveillance was created in 1995 to support exchange and dissemination of authoritative scientific information within the part of public health community involved in the field of infectious disease surveillance and control, at a time when European surveillance networks were at an early stage of growth. Now part of a large network, the publication is entering a new stage: the editorial function will now be hosted at the European Centre for Disease Prevention and Control (ECDC) in Stockholm. This will strengthen the platform for the next stage in Eurosurveillance’s development as the major home of peer-reviewed European information on infectious disease surveillance and control.
Risk and Response Adapted Conventionnal Treatment Strategy In AL Amyloidosis: The French Experience Since 2007
Authors: Arnaud Jaccard, Frank Bridoux, Margaret Macro, Jean Luc Pellegrin, Olivier Tournilhac, Murielle Roussel, Bruno Moulin, Xavier Leleu, Denis Caillot, David Lavergne, Jean Paul Fermand
Journal: Blood (2013)
Abstract 4749: Bromodomain inhibition of the transcriptional coactivators CBP/EP300 as a therapeutic strategy to target the IRF4 network in multiple myeloma
Authors: Patricia J. Keller, Andrew R. Conery, Richard C. Centore, Archana Bommi-Reddy, Karen E. Gascoigne, Barbara M. Bryant, Jennifer A. Mertz, Robert J. Sims
Journal: Cancer Research (2016)

Abstract Pharmacological inhibition of chromatin co-regulatory factors represents a clinically validated strategy to modulate oncogenic signaling through selective attenuation of gene expression. We demonstrate that CBP/EP300 bromodomain inhibition preferentially abrogates the viability of multiple myeloma cell lines. Selective targeting of multiple myeloma cell lines through CBP/EP300 bromodomain inhibition is the result of direct transcriptional suppression of the lymphocyte-specific transcription factor IRF4, which is essential for the viability of myeloma cells, and the concomitant repression of the IRF4 target gene c-MYC. Ectopic expression of either IRF4 or MYC antagonizes the phenotypic and transcriptional effects of CBP/EP300 bromodomain inhibition, highlighting the IRF4/MYC axis as a key component of its mechanism of action. These findings suggest that CBP/EP300 bromodomain inhibition represents a viable therapeutic strategy for targeting multiple myeloma and other lymphoid malignancies dependent on the IRF4 network. Citation Format: Patricia J. Keller, Andrew R. Conery, Richard C. Centore, Archana Bommi-Reddy, Karen E. Gascoigne, Barbara M. Bryant, Jennifer A. Mertz, Robert J. Sims. Bromodomain inhibition of the transcriptional coactivators CBP/EP300 as a therapeutic strategy to target the IRF4 network in multiple myeloma. [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 4749.
Abstract 1985: Oncogenic activation of RNA binding proteins and c-Myc signaling in hepatocellular carcinoma
Authors: Dang T. Hien, Atsushi Takai, Marshonna Forgues, Xin Wei Wang
Journal: Cancer Research (2016)

Abstract Global transcriptomic alterations of both coding and non-coding RNA species are a ubiquitous feature associated with human cancers including hepatocellular carcinoma (HCC). Dysregulation of RNA-binding proteins (RBPs), the key regulators of RNA processing, is one mechanism in which cancer cells select to promote tumorigenesis. We analyzed genomic alterations amongst a family of more than 800 mRNA RBPs (mRBPs) in 1,225 clinical specimens from HCC patients and found that RBPs are significantly activated through gene amplification in a subset of tumors with poor prognosis, suggesting their potential oncogenic roles in HCC progression. Amongst the top candidates, RD binding protein (RDBP) was further characterized for its oncogenic role and effects on the HCC transcriptome. While the activation of RDBP induced an oncogenic phenotype, the abrogation of RDBP in HCC cells significantly decreased cancer associated phenotypes such as cell proliferation, migration/invasion and tumorigenicity in vivo. Further analyses revealed that RDBP-dependent genes were tumor-related with a significant enrichment for c-Myc targets, suggesting interplay between RDBP and c-Myc signaling. Similar data were also found in HCC clinical specimens where c-Myc amplification was uncommon. Consistently, the RDBP-dependent c-Myc target gene signature was able to predict HCC patient survival in two independent cohorts of more than 400 patients. Our results demonstrate that oncogenic activation of RDBP is a novel mechanism that contributes to global transcriptome imbalance, which is selective for the activation of c-Myc oncogenic signaling in HCC. Concurrent with the current model that indicates that c-Myc can promote tumorigenesis through transcription dysregulation, our current work suggests that therapies focused on targeting RDBP may be valuable for clinical treatment of many different tumors with activated c-Myc signaling, including HCC. Citation Format: Dang T. Hien, Atsushi Takai, Marshonna Forgues, Xin Wei Wang. Oncogenic activation of RNA binding proteins and c-Myc signaling in hepatocellular carcinoma. [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 1985.