tbuckley/cabot-search huggingface dataset:
FRI0047 1,25-dihydroxyvitamin D3 downregulates aromatase expression and inflammatory cytokine production in human macrophages
Authors: B. Villaggio, S. Soldano, R. Brizzolara, B. Seriolo, G. Zampogna, P. Montagna, M.A. Cimmino, M. Cutolo
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Aromatases increase estrogen synthesis in inflammatory tissues whereas vitamin D (calcitriol, 1,25-dihydroxyvitamin D3, 1,25(OH)<sub>2</sub>D<sub>3</sub>) seems to decrease the aromatase expression at least in human cancer cells (BCa cells) (1). Interestingly, the aromatase activity is increased together with the estrogen synthesis in the synovial tissue of rheumatoid arthritis (RA) patients, especially at the level of macrophages (2-4). <h3>Objectives</h3> To evaluate in cultures of human activated macrophages the influence exerted by calcitriol on aromatase expression, as a new target for 1,25(OH)<sub>2</sub>D<sub>3</sub>cell modulation of proinflammatory cytokine production (5). <h3>Methods</h3> Cultures of human monocytic THP-1 were activated to macrophages and treated for 24 hours with 1,25(OH)<sub>2</sub>D<sub>3</sub> (10<sup>-8</sup>M), alone or in combination with 17b-estradiol (E<sub>2</sub>, 10<sup>-8</sup>M), in order to evaluate the effects on the intracrine estrogen metabolism (aromatase-driven) and cytokine synthesis. Untreated human macrophages were used as controls (basal condition). P450-aromatase synthesis was evaluated by immunocytochemistry (ICC) and western blot analysis (WB). The expression of P450-aromatase gene (CYP19A1) was investigated by real-time PCR (RT-PCR). Macrophage proinflammatory cytokines IL1-β, IL-6 and TNF-α were evaluated by ELISA and WB. <h3>Results</h3> Interestingly, 1,25(OH)<sub>2</sub>D<sub>3</sub> downregulated P450-aromatase synthesis, CYP19A1-gene expression, and proinflammatory cytokine production (IL1-β, IL-6 and TNF-α) in basal conditions when compared to 1,25(OH)<sub>2</sub>D<sub>3</sub>-untreated macrophages. However and interestingly, the treatment with 1,25(OH)<sub>2</sub>D<sub>3</sub>significantly reduced the increase in P450-aromatase (p&lt;0.001), CYP19A1 gene expression (p&lt;0.001) as well as IL-1bβ, IL-6, TNF-α production (p&lt;0.001) induced by estrogen treatment vs. estrogen-treated (but 1,25(OH)<sub>2</sub>D<sub>3</sub>-untreated) macrophages. <h3>Conclusions</h3> Our data suggest that 1,25(OH)<sub>2</sub>D<sub>3</sub> may downregulate the proinflammatory cytokine production in human activated macrophages by significantly decreasing the aromatase activity, especially in presence of an enhancing estrogenic milieu. Interestingly, this latter hormonal metabolic condition is observed in the synovial tissue and fluid of RA patients of both sexes (2,3). <h3>References</h3> Krishnan AV et al. Endocrinology 2010;151:32-42. Cutolo M et al. Autoimmun Rev. 2011;2 [Epub ahead of print]. Cutolo M. Rheumatology (Oxford) 2009;48:210-12. Le Bail J et al. Steroids. 2001;66:749-57. Zwerina K et al. Ann Rheum Dis. 2011;70:1122-9. <h3>Disclosure of Interest</h3> None Declared
SP0146 Non anti-TNF biologics in axial spondyloarthritis
Authors: J. Sieper
Journal: Annals of the Rheumatic Diseases (2013)

TNF-blockers have been proven to be highly effective in patients with axial spondyloarthritis (axSpA) including patient with anklyosing spondylitis (AS) and non-radiographic axial SpA (nr-axSpA) who show an inadaequate response to conventional treatment. However, there is further need for additional treatment options because (i) about 30% of the patients treated do not reach an ASAS 20 response, and the drop out rate per year is about 15-20%, mostly because of side effects and/or secondary inefficacy. Furthermore, conventional DMARDs such as methotrexate or sulfasalazine are not effective, and the majority of axSpA patients relapse once TNF-blocker treatment is interrupted. On this background new treatment targets are of great interest. Biologics directed against T cells, B cells and directed against various cytokines such as IL-1, IL-6, IL-17 and against the p40chain of IL23 and IL-12 have been tested or are being tested in patients with AS, often in small studies. Therapeutic trials with new small molecules are being planned. The rationale for the selection of these targets and the treatment results will be presented and future development will be discussed. Until now, there is still an unmet need for the treatment of axSpA patients who fail NSAIDs and TNF-blocker treatment. <h3>Disclosure of Interest</h3> J. Sieper Grant/Research support from: Abbott, Merck, Pfizer, Janssen, Consultant for: Abbott, Merck, Lilly, Pfizer, Roche, UCB, Novartis
Ptosis after Swimming in the Red Sea
Authors: Wolf A Lagrèze, Matthias Schaber
Journal: New England Journal of Medicine (2015)

A 52-year-old man presented with a swollen and droopy eyelid that had developed after the patient collided with a school of fish while he was swimming. MRI revealed a granuloma. During surgical excision, two transparent tubular structures were detected and extricated.
GENO-04REGULATION OF GLIOBLASTOMA BY NOVEL LONG NONCODING RNA (lncRNA)
Authors: Frank Attenello, S. John Liu, Martina Malatesta, Hosniya Zarabi, Rebecca Andersen, Alexander Ramos, Daniel Lim
Journal: Neuro-Oncology (2015)

The human genome produces many thousands of long noncoding RNAs (lncRNAs) -transcripts .200nucleotides long with little evidence of protein coding potential.It is now clear that lncRNAs can have critical biological functions and roles in human disease including cancer.Because lncRNAs Overall survival
Vasopressin: Action on WRK-1 Rat Mammary Tumor Cells
Authors: M E Monaco, P H Kohn, W R Kidwell, J S Strobl, M E Lippman
Journal: JNCI Journal of the National Cancer Institute (1982)

WRK-1, a cell line in long-term culture derived from a 7,12-dimethylbenz[a]anthracene-induced rat mammary tumor, responds to physiologic concentrations of vasopressin with increased precursor incorporation into phospholipids and with increased protein accumulation. Because vasopressin has been reported to be a potent mitogen for Hela cells and 3T3 cells, a study was conducted to determine whether it could act as a mitogen for WRK-1 cells. Under no conditions was a clear-cut mitogen response to vasopressin demonstrated.
A6.9 Distinct expression of T-cell homing molecules in human autoimmune lymph node stromal cells upon TLR-3 triggering
Authors: J Hähnlein, TH Ramwadhdoebe, JF Semmelink, IY Choi, NAM Smits, FH Berger, M Maas, DM Gerlag, TBH Geijtenbeek, PP Tak, LBM van Baarsen
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Rheumatoid arthritis (RA) is a prototypic autoimmune disease in which systemic autoimmunity precedes overt synovial tissue inflammation. The aetiology of RA is still unknown and systemic autoimmunity is probably initiated by an unidentified mechanism outside the synovium. Adaptive immune responses are generated in lymphoid tissue where the stromal compartment plays a crucial role in regulating T- and B-cell function. Murine studies have demonstrated that exposure to viral products can alter the interaction between lymph node stromal cells (LNSCs) and T-cells. However, little is known about the ability of human LNSCs to sense pathogens and their response to viral products. Viral infections have also been implicated the initiation and promotion of autoimmunity. <h3>Objective</h3> Here we investigated which Toll-like receptors (TLRs) human LNSCs express and how TLR-3 triggering by polyI:C, affects gene and protein expression of human LNSC derived from lymph nodes obtained of healthy individuals and individuals with evidence of autoimmunity. <h3>Material and methods</h3> We included individuals with arthralgia who were positive for IgM rheumatoid factor and/or anti-citrullinated protein (n = 10; RA risk group), RA patients (n = 12) and healthy controls (HCs, n = 10). All subjects underwent ultrasound-guided inguinal lymph node biopsy and LNSCs were cultured directly from freshly collected biopsies. LNSCs of passage 3–6 were stimulated with polyI:C after which mRNA and protein levels were measured by qPCR, flow cytometry or ELISA. <h3>Results</h3> Cultured human LNSCs expressed TLR1 to 9 with exception of TLR-8 mRNA and the strongest expression was observed for TLR-3. TLR-3 triggering in human LNSCs induced expression of adhesion molecules like VCAM-1 and ICAM-1 and inflammatory cytokines such as IL-6. In addition TLR-3 itself and type I IFN stimulated genes (ISGs) like IRF-7 and IP-10 were upregulated in response to polyI:C. For the ISG MxA we observed a significant lower induction in RA risk individuals compared with HCs (p = 0.0443). Strikingly, the expression of T-cell homing chemokines CCL19 and CCL20 was less induced upon TLR-3 triggering in LNSC obtained from RA risk individuals and RA patients compared with HCs. Likewise, we observed a lower induction of IL-8 protein production in LNSCs derived from RA patients compared with HCs (p = 0.0447). <h3>Conclusions</h3> Human LNSCs express different TLRs and are responsive to TLR-3 triggering. The observed lower induction in T-cell homing chemokines upon TLR-3 triggering in LNSC derived from RA risk individuals and RA patients could indicate a deregulation of antiviral responses in LNSC during autoimmunity.
Periarteritis Nodosa, Australia Antigen and Lymphatic Leukemia
Authors: Michael A. Gerber, Arlin Brodin, David Steinberg, Salvatore Vernace, Chen-Ping Yang, Fiorenzo Paronetto
Journal: New England Journal of Medicine (1972)

A patient who had both lymphatic leukemia and periarteritis nodosa also had persistent Australia antigenemia. Various morphologic forms of Australia antigen were observed in the patient's serum on electron microscopy, but circulating immune complexes were not demonstrable. At autopsy, there was no evidence of persistent hepatitis. Examination of tissues by fluorescent-antibody technic revealed Australia antigen and IgG in the liver-cell nuclei, most probably in the form of immune complexes. Australia antigen was detected in the subacute lesions of periarteritis nodosa in the absence of immunoglobulins or complement.
Abstract 5230: Development of a series of genetically fluorescent human osteosarcoma cell lines with increasing spontaneous metastatic capability
Authors: Yasunori Tome, Hiroaki Kimura, Hiroki Maehara, Fuminori Kanaya, Michael Bouvet, Hiroyuki Tsuchiya, Robert M. Hoffman
Journal: Cancer Research (2011)

Abstract In order to investigate the molecular pathogenesis of human osteosarcoma, a reliable metastatic osteosarcoma animal model is required. Here we report the development of a series of metastatic sublines (LM1-LM4) derived from a human osteosarcoma 143B parental cell line expressing GFP in the nucleus and RFP in the cytoplasm. The sublines have increasing ability to form pulmonary metastases in nude mice after intravenous injection. In vitro proliferation rates of all sublines were similar. When the 143B parental and the metastatic sublines were transplanted orthotopically in the tibia of nude mice, all cell lines were tumorigenic. Primary tumor growth and metastases were imaged with the OV100 Small Animal Imaging System (Olympus Corp., Tokyo, Japan). LM2 and LM3 had higher metastatic capability than the parental 143B. LM1 had higher metastatic capability than LM2 or LM3. LM4 cells resulted in the most pulmonary micrometastases. The number of pulmonary metastases was 8-fold higher in LM4 cells than that with 143B parental cells. This series of metastatic sublines should be a powerful tool to investigate genetic and other factors that promote or inhibit osteosarcoma metastasis and for evaluation of novel anti-metastatic drugs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5230. doi:10.1158/1538-7445.AM2011-5230
P1047 ENTECAVIR EFFECTIVENESS IN NAIVE AND NUC EXPERIENCED PATIENTS WITH CHRONIC HEPATITIS B AND LIVER CIRRHOSIS: INTERIM ANALYSIS OF THE ITALIAN ENTAS COHORT STUDY
Authors: E. Porro, A. Di Leo, A. Marzano, G. Brancaccio, S. Maimone, M. Fasano, A. Grasso, F. Bronte, S. Fagiuoli, T. Santantonio, F. Morisco, E. Petrelli, G. Svegliati Baroni, G. Labbadia, L. Badia, G.A. Niro, M. Vinci, A. Montineri, F. Vinelli, M. Massari, L. Nosotti, G. Galati, G. Missale
Journal: Journal of Hepatology (2014)
Epidermoid metaplasia of the esophagus with an unusual appearance on magnification
Authors: Shinji Kitamura, Yasuyuki Okada, Naoki Muguruma, Hiroshi Miyamoto, Yoshimi Bando, Rika Aoki, Tetsuji Takayama
Journal: Endoscopy (2015)

A 69-year-old man who had a history of a distal gastrectomy for a hemorrhagic duodenal ulcer 50 years earlier was referred to our hospital with an esophageal lesion. The lesion had been detected by esophagogastroduodenoscopy during health screening. The results of his physical examination were normal. He smoked 20 cigarettes daily and drank alcohol almost every day.
Abstract 2237: Nelarabine is safe and effective in adult relapsed or refractory T cellacute lymphoblastic leukemia (T-ALL) and lymphoblastic lymphoma (T-LBL): The Bologna experience
Authors: Cristina Papayannidis, Ilaria Iacobucci, Mariachiara Abbenante, Annalisa Lonetti, Viviana Guadagnuolo, Anna Ferrrari, Emanuela Ottaviani, Antonio Curti, Stefania Paolini, Sarah Parisi, Cristina Clissa, Michele Baccarani, Giovanni Martinelli
Journal: Cancer Research (2011)

Abstract Background. Nelarabine (N) is approved for the treatment of T-ALL and T-LBL that have not responded to or has relapsed after treatment with at least 2 chemotherapy regimens. Aim. To evaluate safety profile and efficacy of N as savage therapy in 16 adult relapsed or refractory T-ALL or T-LBL. Methods. After obtaining an informed consent, 16 patients (median age 33 years, range 19-45, M/F = 13/3) affected by T-ALL (n=10) and T-LBL (n=6) received savage therapy with N (median cycle=1, range 1-3), administered at standard adult dosage (1500 mg/sqm on days 1, 3 and 5, every 21). Four patients were primary resistant to induction treatment, 7 patients were relapsed after two previous chemotherapy regimens (including allogeneic BMT in 4 cases and autologous SCT in 1 case); the remaining 6 patients had a molecular relapsed disease (MRD positive). Molecular characterization was performed, including NOTCH and WT-1 genes mutational status. GEP analysis, according to Ferrando A. stratification (Cancer Cell 2002), is still ongoing. Results. Currently, 12 out of 16 patients are evaluable, due to a too short follow up in the other 4 cases. Seven out of 12 patients obtained a complete remission (CR) (5 T-ALL 2 T-LBL);a partial remission (PR) was documented in 2 cases, with an overall response rate (ORR) of 75%. Median duration of CR was 10 weeks (range 2.8-54+). Among these, 2 out of 4 patients in molecular relapse reached a molecular CR and underwent an allogenic BMT (currently in CR after a median follow up of 12 months). Extra- hematological toxicity, not clearly related to the drug, occurred in 3 cases, determining, a complete and irreversible paraplegia, a condition of mental confusion, and a peripheral neuropathy, respectively. Conclusions. N showed a strong efficacy also in cases with low levels of residual disease, in addition to a good safety profile. Neurological toxicity needs to be strictly monitored. Acknowledgments. European LeukemiaNet, AIL, AIRC, Fondazione Del Monte di Bologna e Ravenna, FIRB 2006, PRIN 2008, Ateneo RFO grants, Project of integrated program (PIO), Programma di Ricerca Regione – Università 2007 – 2009. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2237. doi:10.1158/1538-7445.AM2011-2237
Enantiomer-specific and paracrine leukemogenicity of mutant IDH metabolite 2-hydroxyglutarate
Authors: A Chaturvedi, M M Araujo Cruz, N Jyotsana, A Sharma, R Goparaju, A Schwarzer, K Görlich, R Schottmann, E A Struys, E E Jansen, C Rohde, C Müller-Tidow, R Geffers, G Göhring, A Ganser, F Thol, M Heuser
Journal: Leukemia (2016)
TCT-486 Relationship Between White Blood Cell Count and Final Infarct Size in Patients with ST-Segment Elevation Acute Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention: Analysis from the INFUSE-AMI Trial
Authors: Tullio Palmerini, Sorin Brener, Jan-Henk Dambrink, Martin Fahy, C. Michael Gibson, Jacek Godlewski, Akiko Maehara, Andrzej Ochala, Helen Parise, Gregg Stone, Bernhard Witzenbichler
Journal: Journal of the American College of Cardiology (2012)
SP0133 Systemic Sclerosis and Myositis
Authors: U. Mueller-Ladner
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> Both rare connective tissue diseases, systemic sclerosis and myositis, have been addressed as interesting fields of research and numerous novel aspects have been published in the past year. Epidemiologic data from the large EUSTAR group could show the detailed real world profile of around 10.000 patients with systemic sclerosis. In addition, distinct novel aspects such as cardiovascular morbidity, osteologic dysfunctio and gender-related manifestations of the disease were addressed. Parallel to the acquisition of these data, novel classification criteria for SSc were established. Novel therapeutic approaches included first results from stem cell transplantation but also the effects of immunosuppressants such as mycophenolate on skin fibrosis or neuromodulators on digital ulcers. In SSc but also in myositis, the search for biomarkers and functional autoantibodies continued and led to few but important results. Therapeutic research for myositis reevaluated the current immunomodulators including intravenous immunoglobulins but also novel approaches such as rituximab, the latter with promising results. <h3>Disclosure of Interest</h3> None Declared
Abstract 183: Global knock-down of the cancer epigenome
Authors: Pei-Chi Peggy Hou, Ching-Chu Yen, Kuan-Der Lee, Hao-Chun Chang, Chao-Min Cheng, Yi-Shiuan Lin, H. Sunny Sun, Yu-Sun Chang, Tim H.-M. Huang, Shu-Huei Hsiao, Shaw-Jenq Tsai, Yu-Wei Leu
Journal: Cancer Research (2010)

Abstract Aberrant DNA methylation within the promoter regions is associated with the tumorigenesis, yet no whole epigenomic targeting method has been developed to target all of the aberrant loci. We then aimed to establish a global epigenomic targeting method to efficiently against specific cancer cells. To identify and target all the methylation differences between the estrogen receptor (ER) expressing (MCF7, ER+) versus the nonexpressing (MDA-MB-231, ER−) breast cancer cells, a methylation subtraction method was established. Identified targets was validated by high-throughput sequencing and quantitative PCR, and the efficiency of targeting was validated by the cell death phenotype, increased DNA methylation and reduced expression in the target genes. Targeted methylation within these identified loci specifically killed the MDA-MB-231 cells but not the MCF7 cells either in culture or the tumors grown in immuno-deficient mice. To narrow down the number of targets, we identified and targeted 19 of the estrogen receptor-governed loci that were hypomethylated in the MDA-MB-231, implicating their role in the survival and malignance of these ER− cells. The targeted methylation was sufficient to kill the ER− cells in culture. Among these 19 loci, targeted ENSA methylation alone was sufficient to kill the MDA-MB-231 cell specifically in culture as well as in immuno-deficient mice. Overall, a global targeted methylation methodology was established that could be used to identify and target the methylation differences between two cells. These results indicated that the developed global knock-down method might serve as a whole genome validation and therapeutic alternatives. (Supported in part by NSC 97-2320-B-194-003-MY3, NSC 98-3112-B-194-001 and NSC 97-2627-B-006-003) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 183.
FRI0090 Fulfilling only three of four ACR/EULAR boolean remission criteria is not predictive of subsequent full remission
Authors: P. Studenic, J. Smolen, D. Aletaha
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Remission has become an accepted target of rheumatoid arthritis (RA) treatment, and new remission criteria have been put forward by the ACR/EULAR requiring four criteria to be fulfilled: C-reactive-protein (CRP) ≤1mg/dl, swollen joint count (SJC) ≤1/28, tender joint count (TJC) ≤1/28 and patient global assessment (PGA) ≤1cm on a 10cm visual analogue scale. Only small proportions of patients achieve full remission by these criteria, and it is unclear whether reaching three of the four criteria (“near miss” of remission) already indicates a favourable situation. <h3>Objectives</h3> We aimed to identify the prospective outcome of near miss patients in an outpatient clinic setting. <h3>Methods</h3> We obtained a random single cross-sectional visit of each RA patient documented in a longitudinal RA database, and determined the remission state (full remission: 4/4 criteria; “near miss”: 3/4; or neither: &lt;3/4) at that visit and the subsequent visit. Using the near miss population as the starting point, we identified the variable responsible for the near miss (i.e. CRP, SJC, TJC, or PGA), and the remission outcome at the subsequent visit, descriptively and by non-parametric analyses. <h3>Results</h3> We obtained data of 928 RA patients (80% female; 56% rheumatoid-factor positive; mean disease duration: 8.4 years). On average (±SD) the two subsequent visits were 5±5 months apart; 10% and 11%,respectively, were in full Boolean remission, and 22% and 22% in a near miss status. Of patients with a near miss of remission, 40% remained in this state, 15% improved to full remission, and 45% worsened and lost their near miss status again at the subsequent visit (table). Patients missing remission because of PGA or SJC were much less likely to subsequently achieve full remission than those missing TJC or CRP (12.4% and 12.8% vs. 25.0% and 28.5%, table). Patients with a near miss of remission who subsequently achieved full remission had significantly lower scores of functional impairment (p=0.017), PGA (p=0.004), evaluator global assessment (EGA) (p&lt;0.001) and simplified disease activity index (p&lt;0.001) than those who did not. When near miss status was sustained, then it was due to the same variable at both visits for the great majority (CRP: 100%; PGA: 89%; SJC: 79%); the clear exception here were TJC near miss sustainers, who subsequently had the same reason for the near miss in only 20%, although the patient numbers were low in this group. <h3>Conclusions</h3> Approximately half of the patients missing one variable for remission at a random time point, worsen until the next clinic visit. This indicates that the therapeutic goal of achieving full remission needs to be actively pursued even if a state near to remission is already present. Especially PGA and SJC seem to be significant obstacles on the way to remission. <h3>Disclosure of Interest</h3> None Declared