tbuckley/cabot-search huggingface dataset:
Mir-128 Regulates the Self-Renewal of Breast Tumor-Initiating Cells through HTERT.
Authors: F. Yu, Y. Zhu, C. Gong, Y. Jiao, E. Song
Journal: Cancer Research (2009)

Abstract Background: hTERT (human telomerase reverse transcriptase), which maintains telomere ends by addittion of the telomere repeat sequence TTAGGG, is increased in cancer cells and embryonic stem cells. However, whether hTERT has a role in regulating breast tumor-initiating cells remains unknown. Therefore, the regulation of hTERT in breast tumor initiating cells (BT-IC) would potentially facilitate our understanding of the etiology of breast cancer.Material and Methods: Enrichment for BT-ICs was performed by mammospheres from suspension cultures. The capacity of self-renewal and differentiation of BT-ICs were determined by mammosphere formation, immunohistochemical analysis of epithelial markers and FACS, respectively. TRAP assay was used to detect telomerase activity. The expression levels of hTERT in BT-ICs, with or without lentivirus-mediated mir-128 transduction, were determined by qRT-PCR and western blot. hTERT siRNA or lentivirus-shTERT were used to silence the expression of hTERT in BT-ICs. Differentially expressed mir-128 in BT-ICs was quantified by qRT-PCR and Northern Blot. The expression of BMI1 was determined by Western Blot.Results: hTERT, as well as telomerase activity, had a higher expression in BT-ICs, compared to the differentiated breast cancer cells. BMI1, the target of mir-128, is increased in BT-ICs. Conversely, the expression level of mir-128 is lower in BT-ICs, compared to the differentiated cells. Mir-128 over-expressing reduced the level of BMI1,as well as hTERT, in BT-ICs. Silencing BMI1 by lentivirus-shRNA transfection in BT-ICs leads to the decrease of hTERT protein level. Furthermore, BT-ICs, with hTERT knockdown, lost its ability to form mammospheres and proliferated poorly under differentiating conditions.Conclutions: mir-128 miRNA is reduced in mammospheric BT-ICs, resulting in up-regulation of BMI1, which further brought on the up-regulation of hTERT. And hTERT promotes self-renewal and blocks epithelial differentiation of BT-ICs. Therefore, mir-128 regulates BT-IC stem-cell like properties by BMI1 and hTERT. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5157.
A7.13 Multiparameter flow cytometry analysis: high-dimensional dataset analysis towards a diagnostic test for rheumatoid arthritis
Authors: F Ponchel, L Hunt, AN Burska, R Parmar, S Harrison, R West, P Emery
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Lack of accurate early diagnostic testing of Rheumatoid Arthritis (RA) remains the limiting factor for early treatment to achieve remission. We hypothesised that molecular pathways implicated in RA pathology in the joint can inform a biomarker discovery programme based on flow-cytometry phenotyping of blood cells. Based on published work, we selected 74 subset/phenotypes and used high-dimensional dataset analysis to established their potential value in discriminating patients from an early arthritis clinic with &lt;6 months symptoms who developed RA from those with other rheumatic diseases or non-persistent inflammation. <h3>Methods</h3> 46 patients were enrolled. 6–8 colour flowcytometry was performed using standard protocols. We recorded% of positive cells when 2 populations could be distinguished, and levels of expression (MFI) for single populations. A random forest ordered predictors from these 74 subset/phenotypes according to importance. Then a classification tree was fitted based on the most important factors and finally the variables identified from the classification tree were fitted in a logistic regression. <h3>Results</h3> 23 of the 46 patients had RA, 11 non-persistent inflammation and 12 other rheumatic diseases (AS, SPA, gout, OA and reactive). 47 individual phenotypes were analysed and 36 additional ones using a combination of 2 markers. No difference in lineage representation was found; significant difference were observed for 11/47 subsets (P &lt; 0.025) with 3 more borderline significant (P &lt; 0.075). These suggested particularly high significant differences on CD4 and NKT cells as well as lesser one on B, NK and monocytes. Due to the low number of patients, multivariable analysis was limited. We ran un-supervised cluster analysis which separated 2 groups (RA/non-RA) quite efficiently with 5-RA and 6-non-RA misclassified. A 3-node classification tree using 47 phenotypes classified 20/23 RA patients correctly. The 3 phenotypes showing best discrimination power were IL-6R+NKT-cells, naïve CD4<sup>+</sup>T-cells and CCR6+ monocytes. A logistic regression confirmed that these 3 phenotypes were highly significant phenotypes (P &lt; 0.005). A random forest combining all phenotypes suggested that 8 CD4<sup>+</sup>T-cells phenotypes, 1 CD8<sup>+</sup> T-cells, 2 B-cells, 1 monocyte and 1 NKT-cells have potential value for discriminating RA from non-RA patients based on accuracy. <h3>Conclusion</h3> Despite the small sample size, this analysis demonstrated the value of hypothesis driven marker analysis, with 12 of the 47 phenotypes predicted to have potential showing significant differences. By triangulating different analysis approaches, the robustness of the findings was improved giving confidence in the identification of relevant biomarkers.
The triumph of fingers: mechanical hemostasis for postpolypectomy bleeding using the fingers
Authors: Jiaoyang Lu, Taotao Jiao, Minhua Zheng, Xuefeng Lu
Journal: Endoscopy (2014)

A 67-year-old woman complaining of intermittent lower abdominal discomfort and hematochezia was referred to our endoscopy center. Colonoscopy revealed a 3 × 3-cm sessile polyp located in the sigmoid colon (about 15 cm from the anal verge) ([Fig. 1]). The polyp was hidden behind colonic folds and was difficult to access with a colonoscope. After submucosal injection, the polyp was snared using electrocautery (endocut mode) in a piecemeal fashion ([Fig. 2]).
THU0360 Interferon-gamma release assays in rheumatic patients: Baseline study and in the course of anti-tumor necrosis factor-alpha agents:
Authors: M. Martínez-Morillo, S. Mínguez, L. Mateo, I. Latorre, J. Domínguez, D. Grados, B. Tejera, A. Riveros, S. Holgado, A. Olivé, X. Tena
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> IFN-γ release assays are useful methods for diagnosing LTBI (latent tuberculosis infection). It allow us to detect: a) false negative TST in anergic subjects, b) false positives in BCG-vaccinated patients and c) NTM (non-tuberculous mycobacterias) previously sensitized individuals. All in all, these tests contribute to detect additional cases of LTBI. <h3>Objectives</h3> To establish the usefulness of blood interferon-γ (IFN-γ) release assays in patients with inflammatory rheumatic diseases scheduled for anti-TNF-α treatment and at the follow up. <h3>Methods</h3> Prospective study including rheumatic patients starting an anti-TNF-α agent. All patients underwent TST (two step), a chest radiograph, QuantiFERON GOLD <i>in tube</i> (QFN-G-IT), and T-SPOT.TB. Both tests were repeated after a year of anti-TNF treatment in 21 patients. As control group, 35 adult individuals were included. Concordance were analyzed by Cohen's kappa test. <h3>Results</h3> We included 53 patients (18 male/35 female) candidates for anti-TNF-α (18 rheumatoid arthritis, 13 ankylosing spondylitis, 9 psoriatic arthritis and 13 miscellanea). Mean age was 49±13 years and mean disease evolution was 8.8±8 years. Twenty-four out of 53 patients (45.3%) were receiving systemic steroids, mean daily dose 9.1±11.9 mg/day. BCG vaccination status was documented in 3 patients, 2 referred history suggestive of TB disease and other 3 patients had contact with a confirmed TB case in the past. The results of our study are summarized in Table 1. The differences in the results between the IFN-γ tests were not significant (<i>p=</i>0.675). Interestingly enough, neither T-SPOT.TB nor QFN-G-IT were significant in comparison to TST results (<i>p=</i>0.344 and <i>p=</i>0.727, respectively). Overall agreement between TST and T-SPOT.TB and QFN-G-IT was 77.35% (k=0.33; and k=0.40, respectively), and between both in vitro tests was 83.01% (k=0.57) was observed. Three patients with positive TST and negative T-SPOT.TB and QFN-G-IT, was positive on ELISPOT after stimulation with NTM sensitins. Positive TST, T-SPOT.TB and QFN-G-IT results were not affected by the immunosuppressive therapies. We found 4 conversions (1 patient convert T-SPOT and QFN, and 3 patients convert only T-POT) out of 21 cases evaluated after a year under anti-TNF-α agents. We also observed 2 reversions, one in a patient who had undergone prophylactic treatment for tuberculosis. <h3>Conclusions</h3> In those patients with a high risk of developing active TB, the combined use of TST and IFN-γ may be recommended to increase the overall number of LTBI diagnosis. Reversion is described in subjects who have made prophylaxis. More studies are needed to recommend prophylaxis in conversions. <h3>Disclosure of Interest</h3> None Declared
ROLE OF EARLY CORONARY INTERVENTION IN IMPROVING IN-HOSPITAL MORTALITY IN COMATOSE CARDIAC ARREST PATIENTS WITHOUT ST ELEVATION MYOCARDIAL INFARCTION: A META-ANALYSIS OF OBSERVATIONAL STUDIES
Authors: Hafeez Hassan, Kamala Ramya Kallur, Saurav Chatterjee, Chirag Bavishi, Carlos Gongora, Angela Palazzo, Eyal Herzog, Debabrata Mukherjee, Partha Sardar, Robert Kornberg
Journal: Journal of the American College of Cardiology (2016)
Abstract 1075: Steroid receptor reprogramming of the chromatin landscape: crosstalk at the genomic level.
Authors: Tina B. Miranda, Ty C. Voss, Myong-Hee Sung, Songjoon Baek, Sam John, Mary Hawkins, Lars Grontved, R. Louis Schiltz, Gordon L. Hager
Journal: Cancer Research (2013)

Abstract Crosstalk between the estrogen receptor (ER) and the glucocorticoid receptor (GR) plays an important role in controlling many cellular processes. Physiological interactions between ER and GR are not only important for the development of certain tissues, such as the uterus and bone, but also may play an important role in breast cancer. Recent studies have shown that the GR and ER status in breast cancer is a significant factor for determining the outcome of the disease. However, the mechanistic details defining the cellular interactions between ER and GR are poorly understood. Since the regulation of receptor binding to response elements controls the transcriptional output in response to hormones, it is logical to suspect that co-treatment of cells with corticosteroids and estradiol would have an effect on the genome-wide binding landscapes for GR and ER. Therefore, using chromatin immunoprecipitation followed by high-throughput sequencing we investigated the changes in genome-wide binding of ER and GR upon co-activation and revealed that there is global re-arrangement of steroid receptor binding. Furthermore, we unveiled a novel mechanism dictating the molecular interplay between ER and GR. Genome-wide sequencing of DnaseI hypersensitive sites upon induction of GR shows that GR facilitates selective access of ER to specific sites in the genome by maintaining an accessible configuration at these response elements. In addition, activation of ER can affect chromatin structure at novel GR binding sites, resulting in a new class of GR binding elements. Further studies show that at the sites where ER binding is facilitated by GR, binding to these newly accessible sites is not dependent on the direct binding of ER to its response element. Instead ER is brought to these sites through interactions with other factors, such as AP1. Overall, these studies define genome level interactions between ER and GR whereby the activation of multiple steroid receptors has a dramatic impact on controlling which regulatory elements are accessible to each receptor. The unveiling of this mechanism is important for understanding the molecular interplay between ER and GR in development and in cancer and may represent a general mechanism for crosstalk between receptors. Citation Format: Tina B. Miranda, Ty C. Voss, Myong-Hee Sung, Songjoon Baek, Sam John, Mary Hawkins, Lars Grontved, R. Louis Schiltz, Gordon L. Hager. Steroid receptor reprogramming of the chromatin landscape: crosstalk at the genomic level. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1075. doi:10.1158/1538-7445.AM2013-1075
AB0230 Anorectal involvement in very early systemic sclerosis (SSC)
Authors: G. Lepri, S. Bellando Randone, S. Guiducci, I. Giani, G. Carnesecchi, C. Bruni, J. Blagojevic, A. Radicati, F. Pucciani, M. Matucci Cerinic
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> In SSc anorectal dysfunction is reported in 50-70% with a high impact on patients' quality of life. <h3>Objectives</h3> Evaluation of anorectal involvement and its correlation with esophageal involvement in very early SSc. <h3>Methods</h3> 56 patients (55 female), mean age 49,2±14 years, with very early SSc were evaluated with anorectal and esophageal manometry. The demographic data, anorectal symptoms (fecal incontinence and constipation), Raynaud phenomenon (presence/absence, duration), autoantibodies profile (anticentromere antibodies [ACA], antinuclear antibodies [ANA], anti-Scl70 antibodies [Scl70]), videocapillaroscopy patterns (Normal, Early, Active, Late), puffy fingers, digital ulcers were recorded for all patients. <h3>Results</h3> Anorectal manometry was abnormal in 85% of patients, in these patients an esophageal involvement was found (absence of esophageal peristalsis in 29% of patients and abnormal peristalsis in 67,7% of patients). Anorectal symptoms were found in 5 patients (12,5%). In 16 patients anorectal manometry was not performed because of scarce tolerance of the procedure. <h3>Conclusions</h3> Anorectal disorders are frequently detected in very early SSc even in asymptomatic patients. Our data demostrate that very early SSc is charaterized by contemporary esophageal and anorectal involvement. <h3>Disclosure of Interest</h3> None Declared
MS1-1: Imaging Cancer Invasion In Vivo: Mechanisms and Implications for Therapy.
Authors: P Friedl
Journal: Cancer Research (2011)

Abstract The tumor microenvironment contributes to cancer invasion, growth and survival and thereby impacts tumor responses to therapy. Using infrared-excited multiphoton microscopy in orthotopic fibrosarcoma and melanoma xenografts, we here identify a novel radio- and chemoresistance niche consisting of invading tumor cell strands consisting of several hundred connected cells located within collagen-rich stroma nearby blood and lymph vessels. Despite normoxia, perivascular invasion strands were resistant to high-dose hypofractionated irradiation which otherwise was sufficient to induce regression of the tumor main mass. This invasion-associated chemo-and radioresistance was sensitive to the simultaneous inhibition of β1 and β3 integrins by RNA interference or combined anti-β1/aV integrin antibody treatment leading to proliferation arrest, anoikis induction and subtotal to complete regression of both tumor lesion and invasion strands. Thus, collective invasion is an important invasion mode in solid tumors into a microenvironmentally priviledged perivascular survival niche which conveys radioresistance by integrin-dependent signals. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr MS1-1.
Abstract 5299: Evaluation of apolipoprotein E polymorphism on the aggressive potential of prostate cancer cell lines.
Authors: Godwin O. Ifere, Wendy Demark-Wahnefried, Renee Desmond, Tim R. Nagy
Journal: Cancer Research (2013)

Abstract Introduction: Defective cholesterol-modulating apolipoprotein E (ApoE) isoforms could exacerbate prostatic neoplasia. Recent evidence strongly suggests that specific genetic variants of ApoE control peripheral tissue cholesterol efflux. Defects in ApoE may result in reduced prostate cancer cell cholesterol efflux and enriched concentrations of cholesterol in membranes by reducing clearance. Membrane-rich cholesterol could potentially activate cancer-driven signaling processes. Objective: To determine the relevance of specific ApoE phenotypes as risk factors of aggressive prostate cancer based on their influence on reverse cholesterol transport. Methods: We evaluated ApoE genotypes of the weakly tumorigenic or nonaggressive prostate cancer cell lines (LNCaP and MDA PCA 2b), and the moderate and highly tumorigenic or aggressive prostate cancer cell lines (PC-3 and DU-145). We examined whether ApoE2/E4 variants were associated with tumor aggressiveness via the expression of caveolin-1(cav-1), a cholesterol-regulated pro-carcinogenic gene. Results: We observed that the nonaggressive prostate cancer cell lines carried either the Apo ε3/ε3 or ε3/ε4 alleles, while the aggressive prostate cancer cell lines carried the Apo ε2/ε4 alleles. Our results showed a two-fold increase in the expression of cav-1 in the aggressive cell lines, as opposed to the nonaggressive ones. There was a significantly (p&amp;lt;0.01) greater cholesterol efflux from the nonaggressive cells lines compared to the aggressive cells. Also, the aggressive cell lines retained and localized more cholesterol in their membranes as opposed to the less aggressive cell lines. Conclusions: These results suggest an association between cholesterol status and the aggressive potential of prostate cancer cells. It also highlights the need for further investigation into whether ApoE2/E4 is the dysfunctional phenotype, and whether it has the potential as a biomarker of aggressive prostate cancer. GRANT SUPPORT: NIH R25CA047888 Citation Format: Godwin O. Ifere, Wendy Demark-Wahnefried, Renee Desmond, Tim R. Nagy. Evaluation of apolipoprotein E polymorphism on the aggressive potential of prostate cancer cell lines. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5299. doi:10.1158/1538-7445.AM2013-5299
PTU-058 Community based random blood alcohol level testing without prior notice detects concealed alcohol ingestion in patients with alcoholic liver disease awaiting liver transplantation
Authors: J P Bate, K Rothwell, M A Aldersley
Journal: Gut (2012)

<h3>Introduction</h3> Alcoholic liver disease (ALD) is a common indication for liver transplantation (LT) but recidivism is a significant concern. There is a need for careful assessment and support prior to LT, with monitoring for ongoing alcohol use an important aspect of care for patients on the waiting list (WL). <h3>Methods</h3> Patients listed for LT in the UK are required to sign a contract committing them to lifelong abstinence from alcohol. Scheduled appointments for blood alcohol level (BAL) testing may only uncover the most dependent of those who continue to drink. Our transplant unit, with patient consent, conducts community based BAL testing without prior notice as well as breath testing at the time of admission for LT. We evaluated the role of this process in identifying individuals who continue to drink alcohol while claiming abstinence. An update of a retrospective analysis of all patients with a diagnosis of ALD, who were listed for LT from 2006 to 2011, was performed. Patients with a positive BAL and those removed from the WL were identified. <h3>Results</h3> 206 abstinent patients with ALD were listed for LT after evaluation for risk of recidivism. Four patients on the WL returned a positive BAL at planned appointments and eight upon testing without prior notice. Seven of the latter patients had previously returned negative tests at planned appointments and all were removed from the WL in line with UK national policy. One patient returned a positive test at the time of admission for LT. In addition, two patients admitted to drinking (1 with positive – but below the usual cut-off – BAL tests) and were removed from the WL. <h3>Conclusion</h3> Random BAL testing is a useful tool in identifying ongoing hidden alcohol use in patients with ALD listed for LT. 6.8% of patients with ALD were removed from the WL due to ongoing alcohol ingestion. These patients may have damaged their grafts through ongoing alcohol ingestion and may recover without LT if they were to become abstinent. Identification of these patients is also important in maintaining public confidence in appropriate allocation of scarce donor livers. <h3>Competing interests</h3> None declared.
PROGNOSTIC IMPORTANCE OF LEFT VENTRICULAR MECHANICAL DYSSYNCHRONY IN HEART FAILURE WITH PRESERVED EJECTION FRACTION
Authors: Tor Biering-Sorensen, Sanjiv Shah, Inderjit Ananda, Nancy Sweitzer, Brian Claggett, Bertram Pitt, Marc Pfeffer, Scott Solomon, Amil Shah
Journal: Journal of the American College of Cardiology (2016)
Abstract 2716: Development of tanapox virus for oncolytic therapy
Authors: Krystal N. Seibert, Karim Essani, Bruce E. Bejcek
Journal: Cancer Research (2012)

Abstract Vaccinia virus has been included in the many viruses that have been used to target cancer cells. However, vaccinia virus has some drawbacks in that it infects both tumor and non-tumor cells (Guo, Z. S. etal. 2005 Cancer Research 65: 9991-9998), and hosts often have a pre-existing immunity to it (Hu, Y. etal. 2001 J. Virol. 75, 10300-10308). Due to these drawbacks with vaccinia virus we are developing a poxvirus family member, tanapox virus (TPV), for use as an oncolytic therapy. TPV does not cross-react with vaccinia virus antibodies, replicates in human cells, and results in a relatively mild infection under normal conditions making it safer to work with (Paulose, M. etal. 1998 Microbial Pathogenesis 25, 33-41). Tumor suppressor protein p53 is mutated in over half of all cancers making it a promising target for virotherapy. In this study we characterized the 142R protein of TPV, demonstrating its potential as a conditionally replicating oncolytic virus. By analyzing the sequence of 142R it was determined that the protein has a serine-threonine kinase domain that is homologous to the vaccinia virus B1R gene that has been shown to phosphorylate p53. Viral tropism towards cancer can be enhanced by engineering the virus to be conditionally replicating (Vähä-Koskela, M. J. V. etal. 2007 Cancer Letters 254, 178-216), such as the adenovirus ONYX-015 in which the E1B gene has been deleted, restricting its replication to cells not containing a wild-type p53. When comparing the sequence of 142R to B1R we showed that 142R had 50% identity to B1R. 142R also has the same nucleotide binding, phosphotransfer and proton transfer, ATP binding and catalytic domain indicator regions as B1R. We then created a plasmid with 142R that was transfected into COS-7 cells, harvested and the protein eluted from a cobalt column. This protein was then used in a protein kinase assay against p53. This indicates that the 142R protein of TPV is capable of interacting with p53 so is a good candidate for creating a conditionally replicating virus. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2716. doi:1538-7445.AM2012-2716
B11
Authors: Anthony K. Mayhood, Stephen R. Bunker, Michael F. Hartshorne, William H. Howard, Michael A. Cawthon, Robert D. Karl, John M. Bauman
Journal: Clinical Nuclear Medicine (1984)

Mayhood, Anthony K.; Bunker, Stephen R.; Hartshorne, Michael F.; Howard, William H. III; Cawthon, Michael A.; Karl, Robert D. Jr.; Bauman, John M. Author Information