tbuckley/cabot-search huggingface dataset:
FRI0113 Persistently High Disease Activity According to the ASDAS is Associated with Accelerated Radiographic Spinal Progression in Patients with Axial Spondyloarthritis
Authors: D. Poddubnyy, H. Haibel, J. Braun, M. Rudwaleit, J. Sieper
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Methods</h3> Altogether 177 patients with definite axial SpA (100 with ankylosing spondylitis (AS) and 77 with non-radiographic axial SpA) from the German Spondyloarthritis Inception Cohort (GESPIC) were included in the current study. Spinal radiographs (cervical spine lateral views, lumbar spine lateral and anteroposterior views) were scored according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) system and for the presence of syndesmophytes. Clinical and lab data were collected at baseline and every 6 months thereafter. Time-averaged values of the CRP-based ASDAS, BASDAI and CRP over two years were calculated. <h3>Results</h3> Rates of radiographic spinal progression were remarkably increased in patients with very high disease activity (time-averaged ASDAS&gt;3.5) – table. There was a significant inter-group difference in rates of syndesmophyte formation between the groups of patients with ASDAS&lt;1.3, 1.3≤ASDAS≤3.5, and ASDAS&gt;3.5. Patients with very high disease activity had significantly higher odds for syndesmophyte formation as compared to patients with lower disease activity: odds ratio (OR)=5.5 (95%CI 1.89-16.04). In the logistic regression analysis, mSASSS progression by ≥2 points over two years was significantly associated with the time-averaged ASDAS: OR=1.58 (95%CI 1.02-2.44). Even stronger was the relationship between ASDAS and syndesmophyte formation/progression: OR=2.64 (95%CI 1.50-4.64). Interestingly, the association of ASDAS with syndesmophyte formation remained significant even after adjustment for time-averaged CRP: OR=2.16 (95%CI 1.13-4.11). When further known risk factors for radiographic spinal progression (syndesmophytes at baseline and smoking) were included in the model, the association of syndesmophyte formation with disease activity according to the ASDAS become slightly weaker: OR=1.91 (95%CI 0.99-3.69). In the univariate analysis, there was a significant association of syndesmophyte formation with the time-averaged CRP: OR=1.08 (95%CI 1.04-1.12), but no significant association with the BASDAI: OR=1.19 (95%CI 0.96-1.46). Similar associations were observed also for mSASSS worsening by ≥2 points over 2 years. <h3>Conclusions</h3> Persisting very high disease activity according to the ASDAS is associated with radiographic spinal progression in axial SpA patients with disease duration &lt;10 years. As demonstrated in the multivariate analysis, this effect is at least partially independent of the effect of CRP. We can hereby confirm such a recently described association found in AS patients with long-standing disease [2]. <h3>References</h3> Poddubnyy D, et al. Arthritis Rheum 2012;64:1388-98. 2. Ramiro S, et al. Arthritis Rheum 2013;65(Suppl):S1215-6. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3578
Abstract C68: Transforming growth factor-beta and vascular endothelial growth factor are enhanced in plasma of breast cancer patients resistent to hormone therapy
Authors: Eva Zavadova, Bohuslav Konopásek, Michal Vocka, Lubos Petruzelka
Journal: Cancer Research (2011)

Abstract Even with high therapeutic efficacy of first-line hormonal treatment, most patients with metastatic breast cancer will develop resistance. It appears that a factor contributing to the resistance may be a transforming growth factor-beta (TGF-beta). It is highly immunosuppressive factor that inhibits the natural and specific immunity against tumors and stimulates production of vascular endotelial growth factor (VEGF). Defects in the immune response correlated with poor prognosis and therefore in recent years, research focused on a precise description of the status and function of the immune system and its possible effect in cancer patients. The purpose of the study was to monitor immune responses in patients with hormone receptor-positive breast cancer resistant to hormone therapy, particularly the examination of cellular (CD4, CD8, HLA-DR) as well as humoral immunity. TGF-beta and VEGF production was monitored and we analyzed the changes during hormonal treatment. Methods: Patients included in the research project were implemented routine cancer treatment with hormonal therapy. Basic parameters (histological type and grade, the degree of expression of ER and PR, HER2, and the proliferative marker) were established. Patients were evaluated by a cancer clinical immunologist to exclude immune disorders, allergic or autoimmune origin. TGF-beta and VEGF were mesured by ELISA and antitumor cellular immunity (CD4, CD8, antigen presenting cells) will be measured by flow cytometry. Results: In patients with resistance to hormone therapy mainly depression in cellular immunity was found. Immunglobulin plasma level was decreased as well (mainly IgG4 subtype). Most patients have shown clinical symptoms of immunodeficiency (frequent infections of respiratory or urinary tract, herpetic infections) TGF-beta as well as VEGF plasma level were increased. Significant increase of autoantibodies production was found, particulary in those, involved into blood coagulacion process/antiphospholipide and anticardiolipin autoantibodies. Conclusion: Correlation of these factors with resistance to hormonal therapy, and the state of anticancer immunity could help in the future with the the prediction of resistance to hormonal therapy and contribute to the selection of targeted immune therapy in cancer patients. Acknowledgement: This project was supported by grant IGA NT11168-3/2010. 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 C68.
A1.35 Syndecan-4 deficiency increases inflammation in experimental colitis
Authors: M Fröhling, D Bettenworth, P Paruzel, F Echtermeyer, A Lügering, T Pap, A Stratis
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background and objectives</h3> The ubiquitously expressed transmembrane&nbsp;heparan&nbsp;sulfate proteoglycan Syndecan-4 (Scd4) is able to act in different ways. By binding a variety of molecules, such as cytokines, it can function either as a decoy receptor or it can initiate signalling pathways. It has been also implicated in cell-matrix adhesion, cell migration, differentiation, proliferation and plays an important role during inflammation in rheumatoid arthritis. Our group showed that the loss of Sdc4 has a protective effect in cartilage damage, but in osteopontin-mediated liver damage, in which syndecan-deficiency increased the pathology. Because of these dual effects, we investigate the role of Sdc4 in murine experimental colitis. <h3>Material and methods</h3> We performed DSS-induced colitis in Scd4<sup>-/-</sup> and C57BL/6 WT mice at different time points. First, we analysed the Scd4 protein- and mRNA-level by immunofluorescence staining (IF) and quantitative real-time PCR, followed by measuring the course of colitis by weight loss, colon length, histological scoring of colonic modifications and IF of inflammatory marker cells. Colon-permeability was examined <i>in vitro</i> by using the Evans Blue method. Wound healing effects of Scd4 were analysed <i>in vitro </i>by performing scratch assay analyses withhuman epithelial colon cell line (T-84) and <i>in vivo </i>by colonoscopy of Scd4<sup>-/-</sup> compared to WT mice. <h3>Results</h3> The expression of Scd4 was downregulated in the course of colitis and was elevated during the recovery phase. DSS-treated Scd4<sup>-/-</sup> mice lost dramatically more body weight compared to WT mice and the histological damage according to the Dieleman-Score was markedly elevated in the Scd4<sup>-/-</sup> mice. Also, we found increased invasion of macrophages and granulocytes into the colon. In DSS-treated Scd4<sup>-/-</sup> mice colon-permeability was higher compared to WT mice. The knockdown of Scd4 as well as treatment of T-84 cells with the anti-Scd4 antibody led to a delayed cell migration. Furthermore, colonoscopy experiments showed a decelerated wound healing effect in the Scd4<sup>-/-</sup> mice. <h3>Conclusions</h3> Our data indicate that Scd4 is a major molecule in the homeostasis of the colon epithelium. It exerts protective effects in intestinal inflammation with Scd4 deficiency leading to a higher permeability of the colon as well as a delayed cell migration and diminished wound healing.
UNDERSTANDING THE CARDIOPULMONARY CIRCULATION IN SICKLE CELL DISEASE: USING AN MR AUGMENTED CARDIOPULMONARY EXERCISE TESTING TECHNIQUE
Authors: Emmanuel Ako, Nathaniel Barber, Grzegorz T. Kowalik, Jennifer Steeden, John Porter, John Walker, Vivek Muthurangu
Journal: Journal of the American College of Cardiology (2016)
Abstract 2804: The thiazolidinedione pioglitazone enhances the cancer preventive activity of the rexinoid LG100268 in Her2/neu induced breast cancer
Authors: Iván P. Uray, Jennifer M. Rodenberg, Yun Zhang, Jamal L. Hill, Powel H. Brown
Journal: Cancer Research (2015)

Abstract Two major unresolved issues for breast cancer prevention are the lack of effective preventive agents for estrogen receptor (ER)-negative disease and the potential toxicity of long-term pharmacologic treatment. The ability of retinoid X receptor (RXR)-selective retinoids (rexinoids) to inhibit breast cancer formation independently of ER-status was previously demonstrated in various preclinical models. The goal of our study was to identify ideal druggable targets for the synergistic amplification of the cancer preventive effect of synthetic rexinoids and test the efficacy of a low-dose combination treatment in vivo. We identified the nuclear hormone receptors essential for rexinoid-dependent growth suppression by a high throughput siRNA screen of mammary epithelial cells. Knock-down of ELP, COUP-TF II, GR, TR2, VDR and PPARgamma partially reversed the anti-proliferative effect of the rexinoid bexarotene. Conversely, expression profiling showed that the largest fraction of genes up-regulated by the synthetic rexinoid LG100268 represented regulators of lipid metabolism and putative target genes of the RXR partner receptor PPARgamma. Combination dose-response experiments showed that the PPARgamma agonist pioglitazone was synergistic with low doses (100-300 nM) of LG100268. Long-term daily treatment of MMTV-ErbB2 mice with LG100268 (25 mg/kg) or pioglitazone (20 mg/kg), or their combination resulted in a significant delay of tumor formation, while serum triglyceride levels were not significantly elevated by the combination. Suppression of cell proliferation measured by reduced Ki67 staining was enhanced by the addition of pioglitazone, in both lesions and intact mammary epithelium, while pioglitazone also increased the frequency of cells containing cleaved caspase 3. Furthermore, pioglitazone treatment was associated with a marked induction of microvesicle formation in the adipose issue. These data suggest that the combination of LG100268 and pioglitazone, while potentially targeting the same heterodimer, can invoke distinct biological processes resulting in more effective cancer prevention than achieved by either agent alone, and may be an effective strategy for the prevention of ER-negative breast cancer. Citation Format: Iván P. Uray, Jennifer M. Rodenberg, Yun Zhang, Jamal L. Hill, Powel H. Brown. The thiazolidinedione pioglitazone enhances the cancer preventive activity of the rexinoid LG100268 in Her2/neu induced breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2804. doi:10.1158/1538-7445.AM2015-2804
Abstract 4742: NOTCH2 in breast cancer: Association of SNP rs11249433 with gene expression in ER-positive breast tumors without p53 gene mutations
Authors: Yi-Ping Fu, Hege Edvardsen, Alpana Kaushiva, Juan Arhancet, Tiffany M. Howe, Indu Kohaar, Anushi Shah, Patricia Porter-Gill, Sophie D. Fossa, Bjørn Naume, Stefan Ambs, Anne-Lise Børresen-Dale, Vessela N. Kristensen, Ludmila Prokunina-Olsson
Journal: Cancer Research (2010)

Abstract Background: A recent genome-wide association study (GWAS) has identified a single nucleotide polymorphism (SNP) rs11249433 in the 1p11.2 region as a novel genetic risk factor for breast cancer, and this association was stronger with estrogen receptor (ER)-positive than with ER-negative cancer. We aimed to identify a biologically relevant molecular phenotype of this association. Methods: NOTCH2 expression was measured with custom-designed TaqMan assays on 226 breast tumor samples and 319 blood samples of breast cancer patients. PANTHER analysis based on expression in NCI-60 cell lines (Affymetrix HG-U133 arrays) was used to examine enrichment of pathways, biological processes, or molecular functions for transcripts significantly correlated with NOTCH2 expression. Results: We found evidence of a functional relationship between SNP rs11249433 and expression of the NOTCH2 gene located in the 1p11.2 region. NOTCH2 expression differed in subgroups of 226 breast tumor samples, being lowest in tumors with mutations in the p53 gene and highest in p53 wild-type/ER-positive tumors (p=0.0059). In the latter group, the NOTCH2 expression was particularly increased in carriers of risk genotypes (AG/GG) of rs11249433 when compared to the non-risk AA genotype (p=0.0062). This effect is tissue-specific since rs11249433 was not associated with NOTCH2 expression in blood samples of 319 breast cancer patients. Pathway enrichment analysis of NOTCH2 in the NCI-60 cell lines indicated role of NOTCH2 in integrin signaling, cell-cell interactions, and cell structure and motility. Conclusion: This is the first study to explain genetic association between SNP rs11249433 and breast cancer risk by showing that NOTCH2 expression in breast tumors differs in subgroups of patients and between patients with the risk rs11249433 genotypes when compared to the non-risk genotype. The NOTCH pathway has key functions in stem cell differentiation of ER-positive luminal cells in the breast. Therefore, increased expression of NOTCH2 in carriers of rs11249433 may promote development of ER-positive luminal ductal tumors. The exact mechanisms of regulation of NOTCH2 expression by rs11249433 as well as the role of NOTCH2 in breast cancer development remain to be determined. 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 4742.
IS PREOPERATIVE STRESS TESTING ASSOCIATED WITH 30-DAY POSTOPERATIVE MORTALITY IN PATIENTS PRIOR PCI UNDERGOING NONCARDIAC SURGERY: INSIGHTS FROM THE VETERANS AFFAIRS HEALTH CARE SYSTEM
Authors: Javier Valle, Laura Graham, Thejasvi Thiruvoipati, Ehrin Armstrong, Mary T. Hawn, Thomas Maddox, Steven Bradley
Journal: Journal of the American College of Cardiology (2016)
THREE-DIMENSIONAL ECHOCARDIOGRAPHY ASSESSMENT OF THE SYSTOLIC VARIATION OF EFFECTIVE REGURGITANT ORIFICE AREA IN PATIENTS WITH FUNCTIONAL TRICUSPID REGURGITATION: IMPLICATIONS FOR QUANTIFICATION
Authors: Denisa Muraru, Patrizia Aruta, Csaba Jenei, Marcelo Miglioranza Haertel, Giacomo Cavalli, Gabriella Romeo, Sabino Iliceto, Luigi Badano
Journal: Journal of the American College of Cardiology (2016)
Abstract 243: ABCB5 is functionally required for melanoma growth.
Authors: Brian J. Wilson, Karim R. Saab, Tobias Schatton, Jie Ma, George F. Murphy, Martin Gasser, Ana Maria Waaga-Gasser, Natasha Y. Frank, Markus H. Frank
Journal: Cancer Research (2013)

Abstract Melanoma remains a disease with relatively few beneficial treatments currently available, for late-stage patients. The ATP-binding cassette (ABC) transporter ABCB5 has recently been identified as a cell-surface marker for malignant melanoma initiating cells (MMICs; Schatton et al, Nature 2008), opening a new paradigm for investigation of this aggressive cancer. We have previously demonstrated that these ABCB5+ MMICs can evade the host immune system, and also express VEGFR-1, required for efficient tumor formation. However, the possibility that ABCB5 itself plays a functional role in melanoma tumorigenic growth and progression has not been investigated, until now. To test whether ABCB5 plays a functional role in melanoma growth, or is solely a marker of the cancer stem-cell subset, we generated ABCB5-shRNA knockdown (ABCB5-KD) cell populations in melanoma model cell-lines. To distinguish a bona fide role in intrinsic tumorigenesis from immuno-modulatory effects we subcutaneously injected these cells, versus control cells, into highly immunocompromised NOD/SCID Il2rγ-/- mice and followed tumor progression. We observed a marked and significant downregulation in the ability of ABCB5-KD cells to maintain efficient tumor growth, implying a direct role for ABCB5 in melanoma progression. To obtain mechanistic data to explain this phenotype we generated RNA from ABCB5-KD cells versus controls, and performed microarray analysis of global genomic changes in transcript levels of these cells. We then validated potential “ABCB5-pathway” genes, which also change in the reciprocal manner in an ABCB5 overexpression system that we have developed. Our study links ABCB5 to a direct role in melanoma carcinogenesis, identifies genes and pathways of interest, and uncovers ABCB5 as a putative master-regulator of melanoma. Citation Format: Brian J. Wilson, Karim R. Saab, Tobias Schatton, Jie Ma, George F. Murphy, Martin Gasser, Ana Maria Waaga-Gasser, Natasha Y. Frank, Markus H. Frank. ABCB5 is functionally required for melanoma growth. [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 243. doi:10.1158/1538-7445.AM2013-243
Re: Mutagen Sensitivity as a Risk Factor for Second Malignant Tumors Following Malignancies of the Upper Aerodigestive Tract
Authors: MICHAEL N. POLLAK
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article Re: Mutagen Sensitivity as a Risk Factor for Second Malignant Tumors Following Malignancies of the Upper Aerodigestive Tract Get access MICHAEL N. POLLAK MICHAEL N. POLLAK Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 6, 15 March 1995, Page 458, https://doi.org/10.1093/jnci/87.6.458 Published: 15 March 1995
Targeted Therapy Alone for Acute Promyelocytic Leukemia
Authors: Francesco Lo-Coco, Laura Di Donato, Richard F Schlenk
Journal: New England Journal of Medicine (2016)

Patients with acute promyelocytic leukemia who received all-trans retinoic acid (ATRA) plus arsenic trioxide had an event-free survival rate of 96% at 50 months and an overall survival rate of 99%, better results than with ATRA plus chemotherapy (81% and 88%, respectively).
Abstract 351: Tumor kinome profiling of early systemic disease dissemination in rectal cancer
Authors: Marie G. Saelen, Kjersti Flatmark, Sigurd Folkvord, Rik de Wijn, Heidi Rasmussen, Oystein Fodstad, Anne H. Ree
Journal: Cancer Research (2011)

Abstract Tumor hypoxia as common determinant of resistance to cytotoxic therapies and metastatic behavior is an emerging hypothesis. In baseline tumor biopsy specimens from rectal cancer patients receiving preoperative chemoradiotherapy, using peptide arrays with 144 tyrosine kinase substrates, we have recently shown [Folkvord et al., Int J Radiat Oncol Biol Phys 2010] that phosphopeptide levels generated by tumors with poor response to the chemoradiotherapy were significantly higher than substrate phosphorylation resulting from tumors with good treatment response. The elevated kinase activity in poor-responding tumors was suppressed by the ex vivo addition of the tyrosine kinase inhibitor sunitinib and proved to represent signaling mediated by VEGFR, EGFR, and PI3K/AKT, which is known to be implicated in experimental radiation resistance. Given that these signaling pathways might be involved in adaptive responses to tumor hypoxia, this follow-up study aimed to determine whether the tumor kinase activity signatures might also correlate to systemic disease dissemination. Immunomagnetic detection of tumor cells in bone marrow aspirates was undertaken at the time of diagnosis, and bone marrow micrometastases (BMM) were observed in 33 of 55 (60%) of the patients from whom tumor kinase activity signatures had been obtained. In this new analysis, association between ex vivo sunitinib inhibition of the kinase activity and BMM status was studied, and phosphorylation of 31 tyrosine kinase substrates was significantly more strongly inhibited by sunitinib in the BMM negative patients than in the BMM positive individuals. Interestingly, discriminating phosphopeptides represented proteins derived from signaling pathways implicated in angiogenesis; e.g., signaling mediated by PDGFR, VEGFR, and EPOR, which is a central response to tumor hypoxia and fundamental for metastasis formation. At present, this patient cohort has a median follow-up of 41 months (range 13-58) and has demonstrated significantly poorer metastasis-free survival for the BMM-positive group than for the BMM-negative group (p = 0.008). In conclusion, in this cohort of rectal cancer patients, a tumor phenotype defined by a subset of tyrosine kinase activities insusceptible to the ex vivo inhibitory effect of sunitinib was associated with early systemic dissemination. This project was supported by the EU FP7 grant number 222741 (METOXIA). 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 351. doi:10.1158/1538-7445.AM2011-351