tbuckley/cabot-search huggingface dataset:
Abstract 512: miR-29 expression regulates B7-H3 mediated angiogenesis in medullablastoma
Authors: Ian Purvis, Maheedhara R. Guda, Sujatha Venkataraman, Rajeev Vibhakar, Kiran K. Velpula, Swapna Asuthkar
Journal: Cancer Research (2018)

Abstract B7-H3 (CD276), an immune checkpoint member of the B7/CD28 family, plays a key role in the repression of the immune response by cancer cells. B7-H3 is overexpressed exclusively on tumor and tumor-associated cells, making it an interesting therapeutic target. B7-H3 also appears to play a role outside of immune evasion, contributing to the progression of cancer via invasion, migration, and angiogenesis. Our preliminary data have confirmed the presence of B7-H3 in highly aggressive MYC+ medulloblastoma (MB) tumors. Data-mining studies revealed that B7-H3 is highly expressed across the subgroups of MB, and is correlated with MYC expression in Group 3 and 4 MBs. Recently, miR-29, a tumor-suppressor miRNA, was shown downregulating B7-H3 expression by targeting the 3' UTR of B7-H3 mRNA. Immunoblot analysis of D283 and D458 cells demonstrated reduced expression of both cellular and soluble form of B7-H3 when transfected with miR-29 plasmid. Our preliminary data have shown a novel method of targeting B7-H3 expression by miR-29 in MB cells, inhibiting the ability of MB cells to induce angiogenesis. Because both miR-29 and B7-H3 form an inversely related axis that plays a role in tumor angiogenesis, inhibition of B7-H3 by miR-29 may have potential value in developing novel antiangiogenic treatments in MB. Citation Format: Ian Purvis, Maheedhara R. Guda, Sujatha Venkataraman, Rajeev Vibhakar, Kiran K. Velpula, Swapna Asuthkar. miR-29 expression regulates B7-H3 mediated angiogenesis in medullablastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 512.
Exposure to Secondhand Smoke and Biomarkers of Cardiovascular Disease Risk in Never-Smoking Adults
Authors: AndreaVenn, JohnBritton
Journal: Circulation (2007)

Background— Exposure to secondhand smoke has been associated with a disproportionately high risk of coronary heart disease, thought to be mediated through inflammation, platelet aggregation, and/or endothelial dysfunction. The epidemiological association between objectively measured exposure to secondhand smoke and biomarkers of heart disease risk has not been investigated, however. Methods and Results— We have investigated the cross-sectional relation between secondhand smoke exposure, measured objectively as cotinine, and recognized biomarkers of heart disease risk, namely C-reactive protein, homocysteine, fibrinogen, and white blood cell count, in 7599 never-smoking adults from the Third National Health and Nutrition Examination Survey. Compared with subjects with no detectable cotinine, those with detectable but low-level cotinine (range, 0.05 to 0.215 ng/mL) had significantly higher levels of both fibrinogen (adjusted mean difference, 8.9 mg/dL; 95% CI, 0.9 to 17.0; P=0.03) and homocysteine (0.8 μmol...
The good and the bad of vitamin D inactivation
Authors: Marie B. Demay
Journal: Journal of Clinical Investigation (2018)

While disorders of impaired vitamin D activation and action have long been appreciated, the consequences of abnormalities in pathways leading to the inactivation of vitamin D metabolites have only recently been identified. Two recent articles have shed new light on this area of vitamin D biology. The report by Martineau et al., published in the JCI, describes a pathway in which binding of the vitamin D metabolite 24R,25(OH)2D3 to its effector molecule FAM57B2 plays an important role in endochondral ossification during bone repair. This work follows, and adds to, another recent JCI publication by Roizen et al., showing that rapid inactivation of vitamin D metabolites causes vitamin D deficiency, leading to vitamin D-dependent rickets.
Increased Risk of Acute Myocardial Infarction and Stroke During Hemorrhagic Fever With Renal Syndrome
Authors: Anne-MarieConnolly-Andersen, EdvinHammargren, HeatherWhitaker, MatsEliasson, LarsHolmgren, JonasKlingström, ClasAhlm
Journal: Circulation (2014)

Background—We recently observed that cardiovascular causes of death are common in patients with hemorrhagic fever with renal syndrome (HFRS), which is caused by hantaviruses. However, it is not known whether HFRS is a risk factor for the acute cardiovascular events of acute myocardial infarction (AMI) and stroke. Methods and Results—Personal identification numbers from the Swedish HFRS patient database (1997–2012; n=6643) were cross-linked with the National Patient Register from 1987 to 2011. Using the self-controlled case series method, we calculated the incidence rate ratio of AMI/stroke in the 21 days after HFRS against 2 different control periods either excluding (analysis 1) or including (analysis 2) fatal AMI/stroke events. The incidence rate ratios for analyses 1 and 2 for all AMI events were 5.53 (95% confidence interval [CI], 2.6–11.8) and 6.02 (95% CI, 2.95–12.3) and for first AMI events were 3.53 (95% CI, 1.25–9.96) and 4.64 (95% CI, 1.83–11.77). The incidence rate ratios for analyses 1 and 2 f...
Abstract 2434: Regulation of HIF1a stability by an antisense RNA
Authors: Xin Huang, Huang Huang
Journal: Cancer Research (2018)

Abstract Hypoxia is a hallmark of solid tumors. Hypoxia-inducible factors (HIFs) are the main transcriptional factor that regulate the cellular response to hypoxic stress. HIFs are heterodimers consisting of an oxygen-sensitive alpha subunit (HIFα) and a constitutively active beta subunit (HIF1β, also called aryl hydrocarbon receptor nuclear translocator, ARNT). Among the three homologous HIFα genes, HIF1α, HIF2α, and HIF3α, the functions of HIF1α and HIF2α are best characterized. HIF1α is ubiquitously expressed in essentially all tissue types, while HIF2α expression is more tissue specific. Under normoxia, HIFα is hydoxylated by prolyl-4-hydroxylases (PHDs), targeting it for proteasome destruction mediated by the von Hippel Lindau (VHL) protein, an E3 ubiquitin ligase. Under hypoxic conditions, the activity of PHDs decreases and HIFα is stabilized and forms a dimer with HIF1β. The HIFα/HIF1β dimer is then translocated into the nucleus and binds specifically to the promoters of a large number of target genes involved in adaptation and protection against low oxygen conditions. It is well known that HIFα is stabilized by acute hypoxia and its level decreases under prolonged hypoxic conditions. However, the mechanism remains unknown. Now, we have identified an antisense RNA that regulates the interaction between HIFα and VHL. The induction of the anitsense RNA is responsible for the regulation of HIFα stability under prolonged hypoxia. Our study revealed a novel mechanism regulating HIFα pathway. Citation Format: Xin Huang, Huang Huang. Regulation of HIF1a stability by an antisense RNA [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2434.
Abstract 927: TCPA: An open access resource for cancer functional proteomics data
Authors: Jun Li, Han Liang
Journal: Cancer Research (2018)

Abstract In recent years, tremendous efforts have been made to systematically characterize the molecular profiles of tumor tissues from individuals with cancer, laying a critical foundation for elucidating the molecular basis of tumorigenesis and developing biomarker-based diagnostic, prognostic and therapeutic approaches. In particular, cancer genomic data at the DNA or RNA level are being accumulated at an unprecedented speed. However, comprehensive cancer proteomic data have been relatively limited. Using reverse phase protein arrays (RPPA), we have generated a large collection of cancer protein expression data (&amp;gt;8,000 samples of 32 cancer types from The Cancer Genome Atlas and &amp;gt;650 independent cell lines across 19 lineages). To facilitate access of the broader research community to these RPPA datasets, we have developed a user-friendly data portal, TCPA (The Cancer Proteome Atlas), which can be accessed at http://tcpaportal.org. TCPA currently has two web applications, one is for patient cohort data and the other is for cell line data. Both of them provide three types of modules: (i) “Summary”: the summary module help users check the detailed information about all the datasets curated in our database and provide a user-friendly interface for downloading the data. (ii) “Analysis”: this module provides common used analyses such as correlation, differential, survival and drug sensitivity analysis; and (iii) “Visualization” module provides approaches to examine the global patterns in a specific dataset. share some major analytic and visualization modules. In summary, TCPA represents a highly valuable resource dedicated to cancer functional proteomic data. Compared with other proteomic databases, the primary advantage of TCPA is the availability of quantitative protein expression data over many large cohorts of well-characterized TCGA patient tumors. Moreover, TCPA provides an unprecedented opportunity to validate the findings from TCGA RPPA data through independent sample cohorts and to help select model tumor cell lines for further functional investigation. These unique features of TCPA greatly increase the utility of TCGA proteomic data for both basic research and clinical applications. Citation Format: Jun Li, Han Liang. TCPA: An open access resource for cancer functional proteomics data [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 927.
Humanistic burden of chronic pruritus in patients with inflammatory dermatoses: Results of the European Academy of Dermatology and Venereology Network on Assessment of Severity and Burden of Pruritus (PruNet) cross-sectional trial
Authors: Sabine Steinke, Claudia Zeidler, Claudia Riepe, Philipp Bruland, Iñaki Soto-Rey, Michael Storck, Matthias Augustin, Svetlana Bobko, Simone Garcovich, Franz J. Legat, Andrey Lvov, Laurent Misery, Nani Osada, Adam Reich, Ekin Şavk, Esther Serra-Baldrich, Markus Streit, Jacek C. Szepietowski, Wolfgang Weger, Martin Dugas, Sonja Ständer
Journal: Journal of the American Academy of Dermatology (2018)
Abstract 3729: Developing cetuximab-staurosporine conjugate as the therapeutic medicine in KRAS/BRAF mutated colon cancer cells
Authors: Wei-Ting Chao, Wei-Ting Sun, Hsiang-Ling Chiu, Wan-Chen Wei, Yi-Che Wu, Ling-Yi Kao, Yuan-Chiang Chung, Shih-Hsien Chuang
Journal: Cancer Research (2018)

Abstract Epidermal growth factor receptor (EGFR) is the key receptor for cancer cell growing, cetuximab is the monoclonal antibody that targets EGFR and was approved for treatment of colorectal, head and neck cancer. However, patients with KRAS /BRAF mutation are screened for the resistance. Kinases activities in the signal axes have been demonstrated the role in drug resistance in colon cancer cells. In this study, cetuximab was conjugated with kinases inhibitor staurosporine and the efficacy was examined in KRAS/BRAF mutated colon cancer cells. The cetuximab and staurosprone conjugate was prepared based on the amide bond formation or the thioether bond formation. Both cleavable and non-cleavable linkers were applied to the conjugate. KRAS and BRAF mutated colon cancer cell lines SW480 and HT-29 were treated with cetuximab, staurosporine, cetuximab and Staurosporine combination, cetuximab-staurosporine conjugate, cell viability and the molecular expression were monitored. In the result, staurosporine was demonstrated to suppress cetuximab induced Src activation which may contribute to drug resistance. Wild type cell (SW48) is sensitive (63% viability) to cetuximab treatment compared to BRAF and KRAS mutated cells. Cetuximab-staurosporine conjugate showed twice efficacy than cetuximab on wild type cell, and also resulted in greater toxicity (50% viability) in BRAF/KRAS mutated cells which are resistant to cetuximab treatment. Taken together, cetuximab-staurosporine conjugate has therapeutic potential in BRAF/KRAS mutated colon cancer cells. Citation Format: Wei-Ting Chao, Wei-Ting Sun, Hsiang-Ling Chiu, Wan-Chen Wei, Yi-Che Wu, Ling-Yi Kao, Yuan-Chiang Chung, Shih-Hsien Chuang. Developing cetuximab-staurosporine conjugate as the therapeutic medicine in KRAS/BRAF mutated colon cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3729.
Abstract 16503: Plasma Proteomics Reveal Greater Upregulation of Thrombomodulin in Patients Treated with Rivaroxaban Compared with Warfarin
Authors: Mark Chan, Min Lin, Derek Cyr, Joseph Lucas, Will Thompson, Arthur Moseley, Hitoshi Ueda, Mariko Kajikawa, Richard C Becker
Journal: Circulation (2012)

Background: Plasma proteins mediate thrombogenesis, inflammation, endocardial injury and structural remodeling in atrial fibrillation (AF). Objectives: We hypothesized that anticoagulation with rivaroxaban, a direct factor Xa inhibitor, would differentially modulate biologically-relevant plasma proteins compared with warfarin, a multi-coagulation protein antagonist. Patients/ Methods: We performed unbiased liquid chromatography/tandem mass spectroscopy and candidate multiplexed protein immunoassays among Japanese subjects with non-valvular chronic AF who were randomly assigned to treatment with 24 weeks of rivaroxaban (n=93) or warfarin (n=94). Results: Nine metaproteins -fibulin-1 (P=0.0033), vitronectin (P=0.0010), hemoglobin α (P=0.0012), apolipoprotein C-II (P=0.0017), complement C5 precursor (P=0.0026) and coagulation factor XIIIB (P=0.0032) apolipoprotein H (P=0.0023), coagulation factor XIIIA (P=0.0026) and insulin-like growth factor-binding protein complex acid labile subunit (P=0.0018) - were dif...
Tumor Necrosis Factor-α–Converting Enzyme and Tumor Necrosis Factor-α in Human Dilated Cardiomyopathy
Authors: MamoruSatoh, MotoyukiNakamura, HidenoriSaitoh, HidetoshiSatoh, ChihayaMaesawa, IkuoSegawa, AtsushiTashiro, KatsuhikoHiramori
Journal: Circulation (1999)

Background—Tumor necrosis factor-α (TNF-α) has been implicated in the pathogenesis of dilated cardiomyopathy (DCM). TNF-α–converting enzyme (TACE) has recently been purified and its complementary DNA cloned. The expression of TACE results in the production of a functional enzyme that has precursor TNF-α in the mature form. The aim of this study was to determine whether TACE is expressed with TNF-α in myocardium and whether levels of TACE and TNF-α are related to clinical severity of DCM. Methods and Results—Endomyocardial tissues were obtained from 30 patients with DCM and 5 control subjects. TNF-α and TACE mRNA levels were measured by a novel real-time quantitative reverse transcriptase–polymerase chain reaction method. Expression of TNF-α and TACE proteins was determined by immunohistochemical analysis. TNF-α mRNA was expressed in DCM patients (TNF-α/GAPDH ratio 0.85±0.24) but not in control subjects. TACE mRNA expression was significantly greater in DCM patients than in control subjects (TACE/GAPDH rat...
Abstract 962: Testing T cell co-potentiation as an antitumor therapeutic strategy in humanized mouse models
Authors: Alfreda D. Nelson, Laura Elsbernd, Adam G. Schrum, Diana Gil Pages
Journal: Cancer Research (2018)

Abstract We recently described the concept of T cell co-potentiation as means to target antigen recognition by T cells to achieve antitumor immunotherapy in mouse models. Normally, T cell antigen receptor (TCR) engagement by a strong immunogenic antigen induces a CD3 conformational change that exposes a proline-rich sequence (PRS) in the cytosolic domain of CD3 epsilon (CD3e) to dock cytosolic proteins and contribute to the assembly of the signaling cascade that activates T cell immune function. While induction of CD3 conformational change is required by T cells to achieve productive TCR/CD3 signaling, this molecular event fails to occur when the TCR interacts with poorly immunogenic antigens, like most tumor-associated antigens (TAAs). We found that CD3 conformational change can be exogenously induced on T cells using monovalent Fab fragments (Mono-Fabs) specific for the CD3 complex. Anti-CD3 Mono-Fabs expose the CD3e PRS, but fail to crosslink the TCR/CD3, turning them incompetent to trigger T cell activation in the absence of additional stimulation. However, if TCR has bound a weak antigen, one that fails to induce CD3 conformational change intrinsically, then anti-CD3 Mono-Fabs enable TCR/CD3 signaling, and as a result co-potentiate T cell responses to weak antigenic stimulation. Using a mouse model for melanoma (B6 mice and B16-F10 melanoma cell line), we found that treatment of mice with anti-CD3e Mono-Fabs improved antitumor T cell responses against melanoma in an antigen-dependent manner, and dramatically improved the outcome of complementary T cell immunotherapies. Based on these observations, we hypothesize that T cell co-potentiation using anti-human CD3 Mono-Fabs can be exploited as a novel immunotherapy for cancer patients. We have recently identified one anti-human CD3 Mono-Fab that is capable to induce CD3 conformational change in human T cells and allows the co-potentiation of T cell response to weak antigenic stimulation. Here we present data from human T cells and humanized mouse models using this Mono-Fab that support the potential therapeutic value of exploiting T cell co-potentiation to treat cancer patients. Citation Format: Alfreda D. Nelson, Laura Elsbernd, Adam G. Schrum, Diana Gil Pages. Testing T cell co-potentiation as an antitumor therapeutic strategy in humanized mouse models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 962.
Publisher Correction: Inactivating hepatic follistatin alleviates hyperglycemia
Authors: Rongya Tao, Caixia Wang, Oliver Stöhr, Wei Qiu, Yue Hu, Ji Miao, X. Charlie Dong, Sining Leng, Margaret Stefater, Nicholas Stylopoulos, Lin Lin, Kyle D. Copps, Morris F. White
Journal: Nature Medicine (2018)
Abstract 806: KI2011 is a novel potent FLT3 tyrosine kinase inhibitor in acute myeloid leukemia cells with FLT3-mutation
Authors: Hwani Ryu, Jie-Young Song, Jiyeon Ahn
Journal: Cancer Research (2018)

Abstract More than 30% of patients with acute myeloid leukemia (AML) harbor a mutation with internal tandem duplication (ITD) in the juxtamembrane domain and point mutations in the tyrosine kinase domain of FMS-like tyrosine kinase-3 (FLT3), which results in aberrant activation FLT3 by auto-phosphorylation, and confers poor prognosis. To develop novel FLT3 inhibitors, ten novel oxazole amine derivatives were designed and synthesized based on FLT3 protein structure. Among the synthesized small molecule compounds, KI2011 exhibited selectively inhibitory activities of the class III receptor tyrosine kinases, especially FLT3, wile-type, FLT3-D835Y mutant and FLT3-internal tandem duplication (ITD) mutant isoforms with IC50 values of 25, 9, and 1.2 nM, respectively, determined by an in vitro kinase activity assay. The compound decreased FLT3 phosphorylation and its downstream signaling in MV4-11 cells harboring FLT3-ITD mutation. Treatment of KI2011 selectively inhibited cell proliferation and induced apoptosis of MV411 cells in a concentration-dependent manner, but not in K562 (FLT3 negative) cells. In addition, we found that KI2011 enhanced radiosensitivity of MV4-11 cells. The results suggest that KI2011 is a novel potent FLT3 inhibitor that may be further developed in the preclinical studies as a therapeutic agent in AML treatments. Citation Format: Hwani Ryu, Jie-Young Song, Jiyeon Ahn. KI2011 is a novel potent FLT3 tyrosine kinase inhibitor in acute myeloid leukemia cells with FLT3-mutation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 806.
Abstract 12700: Novel Method For Noninvasive Myocardial Work Analysis in Patients With Left Bundle Branch Block
Authors: Kristoffer Russell, Morten Eriksen, Lars Aaberge, Nils Wilhelmsen, Espen W Remme, Anders Opdahl, Kristina H Haugaa, Thor Edvardsen, Otto A Smiseth
Journal: Circulation (2011)

Background: Left bundle branch block (LBBB) causes a heterogeneous work distribution in the left ventricle (LV). The aim of cardiac resynchronization therapy (CRT) is to synchronize LV contraction ...
Abstract 12041: Comparison of Second-Generation Drug-Eluting Stent With First-Generation Drug-Eluting Stent for the Treatment of Left Main and/or Three-Vessel Disease: Propensity Matched Analysis
Authors: NorihiroKobayashi, ToshiyaMuramatus, ReikoTsukahara, YoshiakiIto, HiroshiIshimori, KeisukeHirano, MasatsuguNakano
Journal: Circulation (2014)

Background: The efficacy of second-generation drug-eluting stent (DES) for left main disease (LM) and/or three vessel disease (3VD) remains unclear. Methods: Between April 2008 and January 2013, 326 patients with LM and/or 3VD were treated by percutaneous coronary intervention. Among these patients, 154 patients were treated with first-generation DES and 137 patients were treated with second-generation DES. We performed propensity matching to minimize the impact of baseline confounding factors. Target lesion revascularization (TLR) and major adverse cardiac events (MACE) were compared between the two groups at 3 years. Results: After propensity matching, there were 101 patients in each group. The incidence of TLR and MACE at 3 years was higher in first-generation DES compared with second-generation DES (TLR: 23.8% vs. 7.9%; P=0.003, MACE: 31.7% vs. 12.9%; P=0.002). Regarding the analysis stratified by the SYNTAX score, incidence of TLR and MACE in low and intermediate SYNTAX scores tended to be higher in ...
Self‐Assembled Nanomedicines for Anticancer and Antibacterial Applications
Authors: Lingyun Zhou, Tian Qiu, Fengting Lv, Libing Liu, Jianming Ying, Shu Wang
Journal: Advanced Healthcare Materials (2018)

Abstract Self‐assembly strategies have been widely applied in the nanomedicine field, which provide a convenient approach for building various structures for delivery carriers. When cooperating with biomolecules, self‐assembly systems have significant influence on the cell activity and life process and could be used for regulating nanodrug activity. In this review, self‐assembled nanomedicines are introduced, including materials, encapsulation, and releasing strategies, where self‐assembly strategies are involved. Furthermore, as a promising and emerging area for nanomedicine, in situ self‐assembly of anticancer drugs and supramolecular antibiotic switches is also discussed about how to regulate drug activity. Selective pericellular assembly can block mass transformation of cancer cells inducing cell apoptosis, and the intracellular assembly can either cause cell death or effectively avoid drug elimination from cytosol of cancer cells because of the assembly‐induced retention (AIR) effect. Host–guest interactions of drug and competitive molecules offer reversible regulations of antibiotic activity, which can reduce drug‐resistance and inhibit the generation of drug‐resistant bacteria. Finally, the challenges and development trend in the field are discussed.