tbuckley/cabot-search huggingface dataset:
CCR5 <sup>+</sup> T-bet <sup>+</sup> FoxP3 <sup>+</sup> Effector CD4 T Cells Drive Atherosclerosis
Authors: Jie Li, Sara McArdle, Amin Gholami, Takayuki Kimura, Dennis Wolf, Teresa Gerhardt, Jacqueline Miller, Christian Weber, Klaus Ley
Journal: Circulation Research (2016)

Rationale: CD4 T cells are involved in the pathogenesis of atherosclerosis, but atherosclerosis-specific CD4 T cells have not been described. Moreover, the chemokine(s) that regulates T-cell trafficking to the atherosclerotic lesions is also unknown. Objective: In Apoe −/− mice with mature atherosclerotic lesions (5 months of high fat diet), we find that most aortic T cells express CCR5 and interferon-γ with a unique combination of cell surface markers (CD4 + CD25 − CD44 hi CD62L lo ) and transcription factors (FoxP3 + T-bet + ). We call these cells CCR5Teff. We investigated the role of CCR5 in regulating T-cell homing to the atherosclerotic aorta and the functionality of the CCR5Teff cells. Methods and Results: CCR5Teff cells are exclusively found in the aorta and para-aortic lymph nodes of Apoe −/− mice. They do not suppress T-cell proliferation in vitro and are less potent than regulatory T cells at inhibiting cytokine secretion. Blocking or knocking out CCR5 or its ligand CCL5 significantly blocks T-cell homing to atherosclerotic aortas. Transcriptomic analysis shows that CCR5Teff cells are more similar to effector T cells than to regulatory T cells. They secrete interferon-γ, interleukin-2, interleukin-10, and tumor necrosis factor. Adoptive transfer of these CCR5Teff cells significantly increases atherosclerosis. Conclusions: CCR5 is specifically needed for CD4 T-cell homing to the atherosclerotic plaques. CCR5 + CD4 T cells express an unusual combination of transcription factors, FoxP3 and T-bet. Although CCR5Teff express FoxP3, we showed that they are not regulatory and adoptive transfer of these cells exacerbates atherosclerosis.
Gastric necrosis following intragastric balloon placement: urgent sleeve gastrectomy as a rescue and definitive procedure
Authors: J. Cienfuegos, V. Valentí, M. Muñoz-Navas, F. Rotellar, J. Arredondo, M. Herraiz, F. Zozaya-Larequi, F. Martínez Regueira, G. Frühbeck, J. Hernández-Lizoain
Journal: Endoscopy (2012)

Use of an intragastric balloon (IGB) as a temporary weight-loss procedure in obese patients has become widespread since 1982 [1] [2]. We present a case of gastric necrosis following balloon refilling, successfully treated with an urgent vertical sleeve gastrectomy.
Abstract 2701: Expression and function of CXCR4 in human salivary gland cancers.
Authors: Nobuyuki Kuribayashi, Daisuke Uchida, Yasusei Kudo, Makoto Kinouchi, Tetsuya Tamatani, Hirokazu Nagai, Youji Miyamoto
Journal: Cancer Research (2013)

Abstract Salivary gland cancers (SGCs) frequently metastasize to cervical lymph nodes and distant organs. Currently, the mechanisms responsible for the metastatic behavior of SGC cells are not fully understood. We previously demonstrated that the stromal cell-derived factor-1 (SDF-1; also known as CXCL12)/CXCR4 system is involved in the establishment of metastasis in oral squamous cell carcinoma. In the present study, we investigated the role of CXCR4 in the metastatic behavior of SGCs. We examined the expression of CXCR4 mRNA and protein in human SGC cell lines by quantitative RT-PCR and western blotting, respectively. The expression of CXCR4 mRNA and protein were frequently upregulated in 5 out of 6 SGC cell lines. On the contrary to the CXCR4 expression, CXCR7, a recently identified second receptor for SDF-1, was detected in all SGC cell lines, expression levels were considerably lower on average compared with that of CXCR4 expression. Functional CXCR4 expression was demonstrated by the ability of these SGC cell lines to migrate toward an SDF-1 gradient. SDF-1 rapidly activated extracellular signal-regulated kinase (ERK)1/2 in SGC cell lines. Immunohistochemical analysis revealed that CXCR4 protein expression was detected in either the nucleus or cytoplasm of cancer cells in 16 out of 20 tissues of adenoid cystic carcinoma (ACC) and in 4 out of 6 tissues of mucoepidermoid carcinoma, which are representative of SGC. Furthermore, ACC cell lines exhibited dramatic metastasis to the lung following intravenous inoculation, whereas AMD3100, a CXCR4 antagonist, significantly inhibited lung metastasis of the cells, ameliorated body weight loss and improved the survival rate of tumor-bearing nude mice. These results indicate that CXCR4 expression contributes to the metastatic potential of SGCs. Citation Format: Nobuyuki Kuribayashi, Daisuke Uchida, Yasusei Kudo, Makoto Kinouchi, Tetsuya Tamatani, Hirokazu Nagai, Youji Miyamoto. Expression and function of CXCR4 in human salivary gland cancers. [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 2701. doi:10.1158/1538-7445.AM2013-2701
Abstract B48: Aurora kinase A plays a central role in the differentiation, survival, and self-renewal of human neuroblastoma SK-N-BE(2)-derived cancer stem cells
Authors: Antonino Maria Sparta, Valentina Potrich, Alessandro Quattrone, Alessandro Provenzani
Journal: Cancer Research (2011)

Abstract Aurora kinase A is upregulated in numerous types of cancers. Since this protein is involved in mitotic spindle formation and cell cycle progression, its dysregulation leads to aberrant chromosomal segregation and consequent aneuploidy. It has been clarified that Aurora A is a key player in neuroblastoma because of its ability to protect the oncogene product N-myc from degradation, and the over-expression of the two of them represents a negative prognostic factor. Neuroblastoma usually develops in children and, up to the present time, the available pharmacological therapies have proven inadequate to treat the MYCN amplified sub-type of cancer, which is the most aggressive and malignant form of the tumor. Therefore, there is an urgency to develop new strategies that will improve its treatment. A novel approach to contrast cancer development and relapse is to target the subpopulation of the tumor initiating cells (or cancer stem cells), due to their multi-drug resistance and self-renewal abilities. In this study, we have employed the SK-N-BE(2) cell line as an in vitro human neuroblastoma model, and compared the effects of Aurora A inhibition on the whole population (WP) and on the derived neurospheres (NS) obtained by their continuous growth in selective medium. We tested the effects of both a specific Aurora A inhibitor, ENMD-2076, and a pan-Aurora isoforms blocker, VX-680, for their influence over cellular physiology, morphology and signaling. The specificity of the results was confirmed by the use of a validated Aurora A siRNA. In SK-N-BE(2) WP and NS, our findings confirmed the ability of Aurora A to protect N-myc from degradation. Moreover, the isolation and characterization by FACS, confocal microscopy and immunoblotting of an aldehyde dehydrogenase-positive side population, confirmed the presence of a fraction of cells with self-renewal capabilities and stem-like properties. The analysis of the signaling network of Aurora A showed functional relationships with the transcription factor STAT3, which is associated with neuronal survival and differentiation, after IL-6 challenge. Furthermore, either Aurora A pharmacological block or silencing induced the phosphorylation of the microtubule associated protein 2 (map2) specifically in the NS, an event that maintains the microtubule in a dynamic state, which is a prerequisite for neurite outgrowth. Our results suggest that Aurora A represents an amenable target for the treatment of neuroblastoma, and gives new insights into its role in regulating neuronal plasticity and differentiation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr B48.
Abstract P5-05-13: HER2-Induced MMP-1 Expression Is Mediated by HER1 Though AR, EGF, and TGF Independent of HER3 through HRG in Breast Cancer Cells
Authors: HH Jung, YH Park, JS Ahn, Y-H. Im
Journal: Cancer Research (2010)

Abstract introduction. However, one of plausible explanation for resistance to trastuzumab is associated with HER dimerization. Furthermore, HER3 seems to be the preferred dimerization partner when signaling occurs through the PI3K pathway and, as such, is emerging as a key target for inhibition of HER signaling. Recently, we reported that HER2 could induce enhanced MMP-1 expression. In addition, this up-regulation of MMP1 expression was shown to be mediated MAPK pathway synergized with ER. Heregulin (HRG) acts as a preferential ligand for HER3 and/or HER4 receptors. Upon binding, HRG activates the EGFR/HER2 receptors via dimerization with HER3 and/or HER4. In the other words, HRG-β was reported to promote MMP-7 expression via HER2-mediated AP-1 activation in MCF-7 cells. In addition, MMP-9 is associated with HRG-≥1/HER2 aggressive phenotype of breast cancer. Based on these backgrounds, we conducted this study to test the role of HER3 in breast cancer cells in relation to the expression of HER2 and MMP-1. Our result showed that MMP-1 and MMP-13 expressions were up-regulated via EGF and amphiregulin (AR) independent of HRG in HER2 transfected MCF-7 and SK-BR-3 breast cancer cells through Western immunoblotting and quantitative RT-PCR. Enhanced MMP-1 and MMP-13 expressions were markedly decreased by treating HER2 targeting agents in AR, EGF, and TGF-β stimulating cell lines, while these findings were not observed in HRG1-β and HRG1-β stimulating cell lines in quantitative RT-PCR. In addition, these findings were reversed by treating siEGFR and siHER2, not by siHER3. Consequently, we could confirm the downstream pathways were mediated by MMP-1 AP-1 not by HRG1-β, nor HRG1-β with EMSA. This study showed that HER2-induced MMP-1 expression was mediated by HER1 though AR, EGF, and TGF independent of HER3 through HRG in breast cancer cells. This result implies that the dimerization responsible for MMP-1 up-regulation by HER2 is HER1/HER2, not HER2/HER3. Further implications of MMP-1 in HER2 overexpressing breast cancer through HER1 are going to following. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-05-13.
A case of autochthonous human Dirofilaria infection, Germany, March 2014
Authors: D Tappe, M Plauth, T Bauer, B Muntau, L Dießel, E Tannich, P Herrmann-Trost
Journal: Eurosurveillance (2014)

In March 2014, an infection with the nematode Dirofilaria repens was diagnosed in a German citizen in the federal state of Saxony-Anhalt. The patient had developed an itching subcutaneous nodule containing a female worm, which was identified as D. repens by 12S ribosomal ribonucleic acid (rRNA) gene sequencing. Autochthonous human D. repens infections have not been described in Germany so far, but this finding is consistent with the recent detection of D. repens in mosquitoes from east Germany.
AB0518 Synovial biomarkers in peripheral spondyloarthritis.
Authors: L. Cozzi, M. Felicetti, F. Oliviero, P. Sfriso, F. Lunardi, F. Calabrese, M. Vezzù, L. Costa, F. Caso, R. Stramare, L. Rubaltelli, J. M. Dayer, L. Punzi, U. Fiocco
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> To analyse a panel of synovial fluid (SF) and synovial tissue (ST) biological markers expression at single joint level to find candidate biomarkers in resistant peripheral spondyloarthritis (SpA). <h3>Methods</h3> Twenty seven resistant SpA patients with knee joint synovitis, included in an Intra-articular (IA) TNF alpha blocking open-label study<sup>1</sup>, were treated with biweekly four IA Etanercept injections (12.5 mg) in a single knee joint. The primary outcome (Thompson's knee index: THOMP) and secondary outcomes were assessed at baseline and at week 8 of the study. The secondary outcomes are: C-reactive protein; Knee Joint Articular Index (KJAI), Health Assessment Questionnaire disability index (HAQ-DI), maximal synovial thickness by gray-scale ultrasonography (US-MST), synovial tissue cluster differentiation CD45+ mononuclear cell (ST-CD45+), synovial tissue-CD31+ vessels (ST-CD31+), and along with levels of synovial fluid (SF) soluble inflammation makers such as Interleukin 1ß (SF-IL 1ß), Interleukin 1 Receptor antagonist (SF-IL 1Ra) and Interleukin 6 (SF-IL 6). <h3>Results</h3> At the end of the study, composite clinical indexes, US-MST, ST and SF biological markers were significantly reduced compared to baseline. There was a significant correlation between CRP and THOMP, or KJAI, or HAQ-DI, or SF-IL 1Ra; between KJAI and THOMP or US-MST; between ST-CD45+ and THOMP, or KJAI or ST-CD31+, or SF-IL 1ß; between SF-IL 6 and THOMP, or KJAI, or SF-IL 1ß, or SF-IL 1Ra; between SF-IL 1 Ra and SF-IL 1ß. Comparing pre- versus post-IA Etanercept injection changes (Δ), we found a significant correlation between ΔCRP with ΔSF-IL 1ß, ΔKJAI with ΔTHOMP and ΔSF-IL 6; Δ HAQ with ΔSF-IL 6; ΔST-CD-45+ with ΔSF-IL 1ß; ΔSF-IL 6 and ΔSF-IL 1ß; ΔSF-IL 1Ra with ΔSF-IL 1ß and ΔSF-IL 6. <h3>Conclusions</h3> The significant association at single joint level of composite clinical indexes to inflammatory soluble markers and to synovial tissue marker expression, as well as between clinical and synovial biomarkers changes following IA-anti TNF-alpha blockers treatment, suggest that CD45+ in synovial tissue and IL-6 and IL-1β in SF may be considered potential biomarkers of the peripheral SpA response to IA TNF- alpha blocking. <h3>References</h3> Fiocco U. et al: Synovial Biomarkers in Psoriatic Arthritis. J Rheumatol Suppl. 2012 Jul;89:61-4. doi: 10.3899/jrheum.120246 <h3>Disclosure of Interest</h3> None Declared
Cancer Is Focus of Biotechnology Research: U.S. Leads Growing Field
Authors: Kara Smigel
Journal: JNCI Journal of the National Cancer Institute (1989)

Cancer Is Focus of Biotechnology Research: U.S. Leads Growing Field Get access Kara Smigel Kara Smigel Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 81, Issue 13, 5 July 1989, Page 974, https://doi.org/10.1093/jnci/81.13.974 Published: 05 July 1989
The Management of Thrombosis in the Antiphospholipid-Antibody Syndrome
Authors: Munther A. Khamashta, Maria Jose Cuadrado, Fedza Mujic, Nick A. Taub, Beverley J. Hunt, Graham R.V. Hughes
Journal: New England Journal of Medicine (1995)

The antiphospholipid-antibody syndrome is a thrombophilic disorder in which venous or arterial thrombosis, or both, may occur in patients with antiphospholipid antibodies. The optimal treatment of these patients is unclear. We assessed the efficacy of warfarin, low-dose aspirin, or both in the secondary prevention of thrombosis in patients with the syndrome.One hundred forty-seven patients (124 [84 percent] of whom were female) with the antiphospholipid-antibody syndrome and a history of thrombosis were studied retrospectively. The syndrome was primary in 62 patients and was associated with systemic lupus erythematosus in 66 patients and lupus-like disease in 19. Each patient's history was reviewed.One hundred one patients (69 percent) had a total of 186 recurrences of thrombosis. The median time between the initial thrombosis and the first recurrence was 12 months (range, 0.5 to 144 months). Treatment with high-intensity warfarin (producing an international normalized ratio of > or = 3) with or without low-dose aspirin (75 mg per day) was significantly more effective (P < 0.001 by the log-rank test) than treatment with low-intensity warfarin (producing an international normalized ratio of < 3) with or without low-dose aspirin or treatment with aspirin alone in preventing further thrombotic events (recurrence rates per patient-year, 0.013, 0.23, and 0.18, respectively). The rate of recurrence of thrombosis was highest (1.30 per patient-year) during the first six months after the cessation of warfarin therapy. Complications involving bleeding occurred in 29 patients during warfarin therapy and were severe in 7 (0.071 and 0.017 occurrence per patient-year, respectively).The risk of recurrent thrombosis in patients with the antiphospholipid-antibody syndrome is high. Long-term anticoagulation therapy in which the international normalized ratio is maintained at or above 3 is advisable in these patients.
PTU-179 Social Deprivation In Barrett’s Oesophagus?: Abstract PTU-179 Table 1
Authors: C Caygill, S Bhattacharjee, A Charlett, AJ Fox, P Gatenby, A Watson, C Royston, KD Bardhan
Journal: Gut (2014)

<h3>Introduction</h3> Squamous oesophageal carcinoma is more prevalent in those with lower socio-economic status. Little is known about this for oesophageal adenocarcinoma (OAC). Anecdotally, OAC has been observed in higher socio-economic groups. Barrett’s oesophagus (BO) is the only known precursor of OAC. This study investigates the association between BO and social deprivation using the 2010 Index of Multiple Deprivation (IMD). <h3>Methods</h3> <i>Patients</i>: 1076 BO diagnosed in Rotherham, between April 1978 and August 2012. <i>IMD:</i> The Office for National Statistics (ONS) divides England into geographical areas each with a similar population size termed Lower Layer Super Output Areas (LSOA). The 2010 IMD comprising a combination of 38 separate indicators is assigned to each LSOA. Every residential postcode is assigned to a LSOA and thus an IMD. This was applied to the postcodes of Rotherham patients at time of BO diagnosis. IMD Quintiles were derived by dividing the distribution of all IMD scores in England into 5 equal categories. The 6257 residential postcodes for Rotherham and the 1076 BO patients were placed in the quintiles relevant to their IMD score. <i>Analysis:</i> Chi square goodness of fit tests were used to compare the observed (O) distribution of BO to the expected (E). Analysis was stratified into those diagnosed before 2001 and 2001 onwards, this being the median year of diagnosis. <h3>Results</h3> (See Table) 2/3rds of all Rotherham postcodes fell into the 2 most deprived quintiles. The O/E IMD distribution of the BO cohort diagnosed before 2001 was similar to that of the Rotherham population but highly significant differences emerged later (p = 0.0001): the two least deprived quintiles had 170 BO patients against 124 expected (37% increase). <h3>Conclusion</h3> No single factor is likely to explain the change observed in the last decade, however, the highly significant difference observed points to a strong association between <i>lower</i> deprivation and <i>increasing</i> risk of BO. To the best of our knowledge this is the first report showing a quantitative link between BO and socio-economic status, which may form a basis for the apparent socio-economic shift between squamous oesophageal cancer and OAC. <h3>Disclosure of Interest</h3> None Declared.
Abstract 4211: Development of a prognostic gene expression signature for invasive bladder cancer
Authors: In-Sun Chu, Sun-Hee Leem
Journal: Cancer Research (2012)

Abstract Bladder cancer comprises of highly heterogeneous tumors and is a malignancy requiring a high surveillance because of the frequent recurrences and the poor clinical outcome when tumors progress into invasive disease. Patients also with superficial and invasive tumors have remarkably different 5-year survival rates reflecting their biological differences. The profiles of gene-expression signatures have become an important and promising way for cancer prognosis and treatment. In addition to their application in cancer class prediction and discovery, microarray gene expression signatures can be used for the prediction of patient survival. Gene expression data were collected from tumor specimens from 165 patients with Korean bladder cancer. We selected then genes use Cox proportional hazard model whose expression patterns are proportionally associated the length of cancer-specific survival (CFS). The expression levels of 256 probes were correlated with CFS time (p&amp;lt;0.005). In poor prognosis subtype, for example, the expression of STK6 (Aurora kinase A), AURKB (Aurora kinase B), and TPX2 (regulator of Aurora kinases) are all up-regulated. One of the best characterized phenomenon of invasion is Epithelial-to-Mesenchymal Transition (EMT). We can't see either vimentin nor Krt19 over-expressed in better prognosis subtype. 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 4211. doi:1538-7445.AM2012-4211
THU0488 Efficacy and Safety of Biologic Agents for the Treatment of Refractory Adult Still’s Disease
Authors: Y. Takakuwa, S. Ooka, H. Ito, T. Kiyokawa, H. Nakano, M. Hiida, H. Yamada, S. Ozaki
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Adult Still’s disease (ASD) sometimes shows resistant to high-dose steroid and conventional immunosuppressive agents. Inflammatory cytokines seems to play a role in the pathogenesis<sup>1)</sup>. Although several biologic agents have been used to treat refractory ASD<sup>2)</sup>, their efficacy and safety are not established yet. <h3>Objectives</h3> To examine the effectiveness and safely of several biologic agents, retrospective analysis was performed. <h3>Methods</h3> We searched our data base for ASD patients who were diagnosed based on Yamaguchi’s criteria from August 2005 to January 2013. Clinical charts of the refractory ASD patients treated with any biologic agents were retrospectively reviewed. Clinical remission of ASD was defined if patients maintained all the following criteria, DAS28/CRP&lt;2.3, no systemic symptoms and normal ferritin levels. <h3>Results</h3> Refractory ASD was identified in 9 out of 84 ASD cases. Male/female ratio: 1:8, average age at 41.1±21.2 (20-76) years old, mean disease duration was 8.0±8.0 (3-29) years. They were treated with one or more biologics during the total 17 clinical courses. (Table) TNF antagonists (infliximab (IFX), adalimumab (ADA) and etanercept (ETN)) succeeded to induce clinical remission in 2 out of 10 clinical courses. Tocilizumab (TCZ) could induce clinical remission in 5 out of 7 clinical course. After switching from TNF antagonists to TCZ, 4 cases were effective out of 5. In the effective cases, the average remission maintenance period of anti-TNF was 28.5 months and TCZ was 40 months. During the treatment with TNF antagonists, severe adverse reaction was observed in 4 cases (ovarian cancer, severe hepatitis, cytomegalovirus infection and infusion reaction in each). No adverse effect was observed during TCZ therapy. <h3>Conclusions</h3> TCZ seems to be highly effective and safe for the treatment of ASD. This hypothesis should be confirmed with larger clinical trials. <h3>References</h3> Hoshino T, Ohta A, Yang D, et al: Elevated serum interleukin 6, interferon-γ, and tumor necrosis factor-α levels in patients with adult Still’s disease. J Rheumatol 1998; 25: 396-8 De Bandt M, Saint-Marcoux B: Tocilizumab for multirefractory adult-onset Still’s disease. Ann Rheum Dis 2009; 68: 153-4 <h3>Disclosure of Interest</h3> None Declared