tbuckley/cabot-search huggingface dataset:
SAT0392 Work Productivity Improvement Associated with Apremilast, an Oral Phosphodiesterase 4 Inhibitor, in Patients with Psoriatic Arthritis: Results of A Phase 3, Randomized, Controlled Trial
Authors: F. Zhang, T. Tencer, S. Li
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Apremilast (APR), an oral phosphodiesterase 4 inhibitor, works intracellularly to regulate inflammatory mediators. The Work Limitations Questionnaire (WLQ) is a reliable tool for assessing work productivity in patients with chronic health conditions. PALACE 1 compared the efficacy and safety of APR with placebo (PBO) in patients with active psoriatic arthritis (PsA) despite prior conventional disease-modifying antirheumatic drugs (DMARDs) and/or biologics. <h3>Objectives</h3> Assess the effect of APR on work productivity and work limitations in the PALACE 1 study. <h3>Methods</h3> Patients were randomized 1:1:1 to PBO, APR 20 mg BID (APR20), or APR 30 mg BID (APR30) stratified by baseline DMARD use (yes/no), and treated for 16 weeks to reach the primary end point. Patients completed the WLQ, a 25-item questionnaire that assesses the impact of chronic health conditions on work performance and productivity, at baseline and Week 16. Work limitations were categorized into 4 domains: physical demands (PDS), mental demands (MDS), time management demands (TMS), and output demands (ODS), which were then used to calculate the WLQ index. <h3>Results</h3> 504 patients were randomized in PALACE 1. Of the 261 patients who completed the WLQ, baseline work productivity and work limitations were similar across treatment groups. At Week 16, APR20 and APR30, vs. placebo, were associated with a greater mean change from baseline in PDS (-5.58 and -6.24 vs. -2.14), MDS (-2.22 and -5.18 vs. 1.15), TMS (-4.03 and -8.76 vs. -4.25), and ODS (-5.92 and -10.3 vs. -1.34), resulting in a greater mean improvement in the WLQ index (-0.01 and -0.03 vs. 0.00), which corresponds to a higher median percent improvement of productivity loss (18.9% and 24.7% vs. -3.7%). Higher productivity improvements were also observed among APR20 and APR30 ACR20 responders at Week 16 – PDS (-11.8 and -7.61), MDS (-8.56 and -11.0), TMS (-7.88 and -15.8), and ODS (-10.6 and -20.1) – resulting in a higher mean improvement in the WLQ index (-0.03 and -0.05), which corresponds to a higher median percent improvement in work productivity (57.9% and 46.8%). <h3>Conclusions</h3> APR20 and APR30 increased work productivity and improved work limitations compared with PBO in patients with active PsA despite prior conventional disease-modifying antirheumatic drugs (DMARDs) and/or biologics. <h3>Disclosure of Interest</h3> F. Zhang Employee of: Celgene Corporation, T. Tencer Employee of: Celgene Corporation, S. Li Employee of: Celgene Corporation <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4419
Evaluation of the Phytochemical Anethole as an Anti-Tumor Agent in MCF-7 Cells.
Authors: C. Chen, M. De Gasperi, R. Salcedo, D. Cavazos, L. deGraffenried
Journal: Cancer Research (2009)

Abstract Background: Chinese herbal medicines have gained considerable interest from the cancer community as potential anti-tumor agents. Both clinical as well as pre-clinical studies have demonstrated that certain Chinese herbal medicines can improve survival, increase tumor response, improve quality of life, and reduce chemotherapy toxicity. The specific mechanisms by which these compounds mediate their effects remain largely unknown, inhibiting their development as clinical agents. One such compound is anethole. Anethole is an aromatic compound that occurs widely in nature as a component of anise, fennel anise myrtle, licorice, and star anise and is used in traditional Chinese medicine as an anti-inflammatory agent. Anethole has been identified as one of the potential phytochemicals with anti-cancer activities that could be developed into clinical treatments for breast cancers.Objective: In this current study, we evaluated the effect of anethole on physiological responses and specific survival pathways in human breast cancer MCF-7 cells.Results: Cell proliferation and cell survival were suppressed in a dose-dependent manner in response to anethole treatment, but these dosages had differential effect on specific pro-survival pathways. Anethole increased the cleavage of Poly (ADP-ribose) polymerase (PARP), suggesting an increase in apoptotic activity, but concurrently increased the expression of pro-survival proteins Bcl-2 and p21 while decreasing the expression of tumor suppressor protein p53. Phosphorylation of Akt kinase and S6 pro-survival proteins were modulated in an alternating pattern with increasing concentrations of anethole. Studies were also conducted to investigate the effect of anethole on the sensitivity of MCF-7 cells to tamoxifen treatments. The effect of tamoxifen on cell proliferation was not affected significantly by co-treatment with anethole but importantly the suppression of cell survival by tamoxifen was enhanced when anethole is present at a concentration of 10-5 M. Preliminary data suggest that one mechanism by which anethole is mediating some of its suppressive effects is through modulation of ER activity, as measured by luciferase assays. Studies are on-going to evaluate the relevance of this modulation to the inhibitory effects of anethole on the MCF-7 cells, as well as the modulation of the signal transduction pathways indicated on survival.Conclusion: These data suggest that the anethole is a potential anti-tumor agent, and that co-treatment of tamoxifen and anethole is a potential approach to sensitize human breast MCF-7 cells to tamoxifen treatments. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3100.
SAT0321 The Absence of SSC Pattern at NFC Carries A 90% Negative Predictive Value for the Classification of Very Early or Established SSC in an Unselected Cohort of Patients with Raynaud's Phenomenon; Experience from A Single Tertiary Centre: Table 1.
Authors: L.-A. Bissell, G. Abignano, F. Del Galdo, M.H. Buch
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Nail-fold capillaroscopy (NFC) patterns of vasculopathy have been well described in systemic sclerosis (SSc) but few studies have reported their predictive value in an unselected cohort of patients with Raynaud9s Phenomenon (RP). <h3>Objectives</h3> To describe the association and predictive value of NFC patterns with a clinical diagnosis of SSc. <h3>Methods</h3> Patients (pts) referred to a tertiary Scleroderma clinic to aid in the diagnosis and management of RP were evaluated by light/video-NFC, performed by a fully trained physician. Data collected included clinical diagnosis, antibody (Ab) status, NFC findings and fulfilment of the VEDOSS or 2013 ACR/EULAR criteria for SSc. Primary RP (pRP) was defined as RP with no features of CTD/Ab. NFC patterns were determined: normal, non-specific, “early”, “active” or “late” SSc patterns as described. <h3>Results</h3> 347 pts were referred to the NFC service between Jan 2009 and Oct 2013; mean (SD) age was 47 (15.2) yrs, 83% were female, 26% smokers (Table 1). On clinical review, 54 (15%) did not have RP, 69 (20%) had primary RP, 52 had SSc (56% ACA+ve, 8% Scl70+ve; 67% lcSSc, 10% dcSSc, 11.5% undefined, 11.5% overlap; at referral, 29% met VEDOSS criteria, 60% met 2013 ACR/EULAR criteria), and 172 (39.5%) had secondary RP (sRP). NFC SSc pattern was detected in 80 (23%) pts: 43 with “early”, 31 with “active” and 6 with “late” pattern. 37 of the 52 patients with SSc had SSc pattern at NFC. Among the other patients with SSc pattern, 30 had sRP, 9 pRP and 4 no RP. Non-specific findings were detected in 8/52 patients with SSc, 62/172 patients with sRP, 33/69 patients with pRP and 21/54 patients with no RP. Of those without a clinical diagnosis of scleroderma (n=295), 41 (14%) met VEDOSS criteria following NFC and 4 (1.3%) the 2013 ACR/EULAR criteria for SSc. Of the 41 pts meeting VEDOSS, 28 (68%) were found to have a SSc NFC pattern. Considering the entire unselected cohort, the detection of SSc pattern on NFC had a sensitivity of 71%, specificity 95%, positive predictive value 84% and negative predictive value 90% for identifying pts who met the VEDOSS or 2013 ACR/EULAR criteria. <h3>Conclusions</h3> Our specialised NFC service improved the detection of SSc in an unselected cohort of pts with RP or suspected CTD. Pts meeting the new ACR/EULAR criteria are more likely to have a SSC NFC pattern than those meeting VEDOSS criteria. The absence of SSc NFC pattern in pts with RP or suspected CTD is very valuable in the exclusion of SSc. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1577
Abstract LB-199: ZEB factors link IL-1β-induced EMT and stem cell phenotypes in colon cancer
Authors: Lei Wang, Yijing Li, Amy Beckley, Loretta Pappan, Jishu Shi
Journal: Cancer Research (2012)

Abstract Up-regulation of inflammatory cytokines such as IL-1β in tumor microenvironment has been associated with progression of human colorectal cancer. However, the exact molecular mechanisms by which inflammatory cytokines promote colon tumor growth are still unclear. Cancer stem cells (CSCs), a distinct subpopulation with self-renewal ability, drug resistance and high oncogenic potential, are thought to be responsible for tumor initiation and progression. Epithelia-mesenchymal transition (EMT), characterized by the repression of E-cardherin expression and increased cell mobility, is associated with enhanced metastasis. The objective of this study is to determine whether IL-1β may promote cancer progression by inducing EMT and colon CSC development. Here, we showed that IL-1β promoted E-cadherin repression in both human colon cancer cell line HCT-116 cells and primary colon cancer cells. Expression of E-cadherin transcription repressors ZEB1 and ZEB2 was up-regulated in IL-1β-treated HCT-116 and primary colon cancer cells, respectively. In addition, IL-1β-treated HCT-116 cells exhibited higher cell migratory ability. Moreover, IL-1β induced the expression of stem-cell marker Bmi-1 in both HCT-116 cells and primary colon cancer cells. IL-1β increased these cells’ ability of sphere formation in serum-free conditions and chemo-resistance; properties associated with colon CSCs. Taken together, these results indicate that IL-1β can induce EMT and promote generation of colon CSCs. More importantly, we found that ZEB1 and ZEB2, but not other E-cadherin transcriptional repressors (such as Snail and Twist), were consistently up-regulated in HCT-116 cells and primary colon cancer cells, respectively, during both processes of IL-1β-induced EMT and sphere formation. This suggests that ZEB factors may mediate IL-1β-induced EMT and generation of colon CSCs. Currently, this hypothesis is under evaluation using shRNAs to knock down ZEB1 in HCT-116 cells. Understanding the role of ZEB factors in IL-1β-mediated EMT and CSC development may lead to the identification of novel molecular targets for colon cancer therapy. 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 LB-199. doi:1538-7445.AM2012-LB-199
734 ASSOCIATION BETWEEN MICA POLYMORPHISM AND THE DEVELOPMENT OF HEPATOCELLULAR CARCINOMA IN PATIENTS WITH CHRONIC HEPATITIS C
Authors: S. Nakamoto, F. Imazeki, T. Kanda, S. Wu, T. Miyamura, A. Tawada, M. Arai, K. Fujiwara, K. Saito, H. Shirasawa, O. Yokosuka
Journal: Journal of Hepatology (2012)
Multicentric infantile myofibromatosis of the small bowel detected by video capsule endoscopy in a child
Authors: L. Alberti, P. Souto Bittencourt, A. Rodrigues Ferreira, R. Rodrigues Da Silva, S. Diniz Carvalho, F. Nunes Cachicolo, M. Bahia, L. Fonseca de Castro
Journal: Endoscopy (2012)

Infantile myofibromatosis (IMF) is a rare group of reactive lesions. Their clinical, radiological, and pathological features may be confused with those of malignancy. The lung and mediastinum are the most common site of IMF in all pediatric age groups [1] [2] [3] [4].
Abstract 3860: Furin is required for processing KISS1 to kisspeptins.
Authors: Sitaram Harihar, Keke M. Pounds, Tomoo Iwakuma, N G. Seidah, Danny R. Welch
Journal: Cancer Research (2013)

Abstract KISS1 is a broadly functional metastatic suppressor that is secreted and processed in the extracellular milieu into small peptides (called kisspeptins (KP)). The enzyme(s) responsible for generation of KP from nascent KISS1 is unknown, although sequence analysis (cleavage at KR or RR dibasic sites) suggests that members of the proprotein convertase family may be involved. We, therefore, hypothesized that enzyme(s) belonging to the proprotein convertase family process KISS1 to generate kisspeptins. To this end, we treated multiple melanomas and breast carcinoma cells overexpressing KISS1 with the proprotein convertase inhibitor Dec-RVKR-CMK and found that KISS1 processing was completely inhibited, strongly consistent with a role for proprotein convertases. To identify specific proprotein convertases responsible for KISS1 processing, we systematically analyzed the mRNA expression of the nine members of this family across numerous cell lines. We found a consistent expression of the three proteases - furin, PC5 and PC7 -suggesting one or combination of these three enzymes to be involved in KISS1 processing. shRNA-mediated knockdown of furin, PC5 and PC7 (individually and in combination) resulted in complete loss of KISS1 processing only in furin knockdown cells; whereas, no effect on processing was observed in PC5 or PC7 knockdown cells. Thus, when combined with previous studies showing post-secretion processing, extracellular furin was identified as the essential enzyme responsible for KISS1 proteolytic cleavage into kisspeptins. [Support: CA134981, Komen SAC110037, National Foundation for Cancer Research, Steiner Family Fellowship in Metastasis Research] Citation Format: Sitaram Harihar, Keke M. Pounds, Tomoo Iwakuma, N G. Seidah, Danny R. Welch. Furin is required for processing KISS1 to kisspeptins. [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 3860. doi:10.1158/1538-7445.AM2013-3860
PREDICTORS OF EARLY, LATE AND VERY LATE (UP TO 12 YEARS) STENT THROMBOSIS FOLLOWING DRUG-ELUTING STENT IMPLANTATION IN DAILY PRACTICE: A SUBANALYSIS OF THE DESIRE REGISTRY
Authors: Ricardo A. Costa, Amanda Sousa, Jose de Ribamar Costa, Adriana Moreira, Galo Maldonado, Manuel Cano, Cantídio Campos, Lucas Damiani, Richardo Pavanello, J. Eduardo Sousa
Journal: Journal of the American College of Cardiology (2015)
Chlamydia trachomatis infection Prevalence varies in general practice
Authors: P Owen, T Crowley, P Horner, J Nelki, E O Caul
Journal: BMJ (1994)

EDITOR, - More is known about the prevalence of Chlamydia trachomatis infections in women in primary care than David Taylor- Robinson mentions.1 Analysis of studies in general practice has raised several more specific problems and hence some more specific solutions. These studies have shown variations both over time and among practices in the prevalence of cervical chlamydial infections, ranging from 0.5% to 10.7%.*RF 2-5* The variations in prevalance can be attributed to the different tests used to detect C trachomatis; the site of the practice (inner city or suburban); whether the patients were symptomatic; and changes in the prevalence of the organism itself. Information on the changing prevalence of C trachomatis in primary care is not routinely available to general practitioners, although such information is available to genitourinary medicine clinics. General practitioners require this information if they are …
Therapy-related adult acute lymphoblastic leukemia with t(4;11)(q21; q23): MLL rearrangement, p53 mutation and multilineage involvement
Authors: R Bigoni, A Cuneo, M Grazia Roberti, S Moretti, C De Angeli, M Dabusti, D Campioni, L del Senno, A Biondi, T Chaplin, BD Young, G Castoldi
Journal: Leukemia (1999)
Abstract P1-17-03: Comparison of Long Term Outcome of Locally Advanced and Inflammatory Breast Cancers Treated with Dose Dense Neoadjuvant Chemotherapy
Authors: S Giacchetti, R Porcher, J Lehmann-Che, A Roquancourt, C Cuvier, AS Hamy, P Bertheau, H de Thé, M Marty, M. Espié
Journal: Cancer Research (2010)

Abstract Background: Inflammatory breast cancers (IBC) have a worse prognosis than locally advanced breast cancer (LABC) (KW Hance, JNCI 2005; 97:966-75). We report a series of LABC and IBC treated with dose dense anthracycline and cyclophosphamide and report the correlation between phenotypic features, pathological complete response (pCR) and disease free survival (DFS). Materials and methods: Between 1990 and 2003, 196 patients (pts) with LABC (105 pts) and IBC (91 pts) treated at St Louis hospital received 6 cycles (c) of dose dense Cyclophophamid (1.2g/m2 d1)-Epirubicin (E) (75mg/m2d1) q2w (SIM regimen). 133 patients had frozen biopsy allowing p53 determination. Surgery was done after chemotherapy. pCR was defined as no residual invasive tumor in breast and lymph nodes. Results: Median follow-up was 110 months. IBC were more often ER negative than LABC(52 % vs 34%), more often triple negative (33 % vs 22 %) and more often TP53 mutations .(60% vs 39 %). pCR in breast and lymph nodes was identical in LABC (17 pts,16%) and in IBC (14 pts, 16 %). Table I Pathological response and factors associated with pCR Negative ER and presence of TP53 mutations were strong predictive factors of chemotherapy efficacy in LABC and less in IBCS. histologically grade 3 was not predictive in IBC. Median disease free survival (DFS) was higher in LABC [103 months (m)] than in IBC (54 m), p=.031. Median Overall survival (OS) was not reached in LABC and was of 134 m in IBC (p = .015). A significant effect of ER status on DFS was found in LABC and IBC. When adjusting for ER, IBC still had a significantly shorter DFS (HR 1.64, 95%CI 1.12 to 2.39, P=.011). Similar results were found for OS. For TP 53, a significant interaction was found with LABC/IBC (p=0.017) with a risk for mutated patients in LABC (p=0.004) and a slight and nonsignificant increased risk in IBC patients (p=0.62). Estimated disease free survival at 15 years Conclusion: High risk patients treated with dose dense cyclophosphamide and anthracyclin have very long survival rate. Negativity of ER and p53 mutations are strong predictive factors of good outcome in LABC but less in IBC. This approach in ER-LABC should be prospectively studied.. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-17-03.
THU0376 Bone Mineral Density in Patients with Advanced Atherosclerosis
Authors: E. Deseatnicova, I. Bancu, L. Groppa, I. Popovici
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> To evaluate lumbar spine and femoral neck bone mineral density (BMD) and T score at lumbar and femoral neck levels in documented coronary artery disease patients. <h3>Methods</h3> We studied spine and femoral neck bone mineral density in 68 angiographically documented coronary artery disease patients (narrowed main coronary vessels more than 50%) and 42 persons with normal angiography. Blood lipid profile was determined in all the participants. Both evaluated groups of patients were similar in age, sex and body mass index (BMI). All the received data were analyzed statistically. <h3>Results</h3> After final adjustment by age, sex and BMI, we found that severity of coronary artery disease independently correlated with Bone mineral density of femur and of lumbal spine. BMD was significantly lower in patients with coronary artery disease (<i>P</i>= 0.04). Femur osteoporosis and osteopenia was found in 26,7 % of patients with coronary artery disease whereas only 12,3% of people with normal angiography had osteoporosis at the level of femur (P= 0.05, OR= 4.42; CI 95%, 1.29-14, 77). Lumbal spine osteoporosis and osteopenia was found in 27,5% and 11,8 % in people with normal angiography (P= 0.05, OR= 4.13; CI 95%, 1.18-12, 23). We also found a strong indirect correlation between total cholesterol and LDL cholesterol levels and bone mineral density at femoral levels (p&lt;0,05). Cholesterol levels and BMD at lumbar level showed a tendency to correlation. Trigicerides level did not show any statistically significant differences with BMD at any level. <h3>Conclusions</h3> We can suppose that coronary artery disease and severity of atherosclerosis may serve as a bone turnover predictor. Thus, recommendation of Bone density measurement to patients with a coronary disease may be valuable for earlier diagnosis and prevention of osteoporosis and fractures. More studies are necessary to elucidate deeper the relationship between osteoporosis and coronary artery disease. <h3>Acknowledgements</h3> Department of Interventional Medicine, Institute of Cardiology of the Republic of Moldova <h3>Disclosure of Interest</h3> None Declared
P2-16-03: Outcomes of Nipple-Sparing Mastectomy (NSM) and Immediate Reconstruction.
Authors: JR Chidester, JR Olson, KE Poruk, JJ Marengo, CB Matsen, L Neumayer, J Agarwal
Journal: Cancer Research (2011)

Abstract Background Nipple-sparing mastectomy (NSM) is the surgical removal of breast tissue that preserves the entire skin envelope including the nipple areola skin (NAS). We report our experience performing NSMs and immediate breast reconstruction for both high-risk breast cancer treatment and prophylaxis over a six-year period at The University of Utah and Huntsman Cancer Hospital. Methods: A retrospective chart review was performed on patients undergoing NSM from April 2005 - April 2011. Data collection included: patient demographics, oncologic details, surgical information (including reconstruction timing and type), and complications (infection, hematoma, seroma, skin necrosis, NAS complication, skin flap loss, premature expander exchange/removal, and capsular contracture). Results: 130 patients underwent 205 NSMs. Of these, 106 (81.5%) patients received mastectomy treatment for cancer while 24 (18.5%) patients were prophylactically treated. 102 NSMs (49.8%) were on breasts with biopsy-proven cancer, while 103 (50.2%) NSMs were on breasts for prophylaxis. All patients were female with a mean age of 44.7 years (range, 16–82 years). 119 (92.2%) patients were Caucasian, 3 (2.3%) were Asian, and 1 (0.8%) was Hispanic. The mean weight was 65.2 kg (range, 42.8 - 98.8 kg) and BMI (n=106) was 23.7 kg/m2 (SE±0.4). 14 (10.9%) and 12 (9.3%) of the patients were known to have a BRCA1 and BRCA2 mutation, respectively. Two (1.6%) patients had a p53 mutation. 172 (83.5%) of the nipples were spared via an 8 cm incision lateral to the midpoint of the areola, while 5 (2.4%) of the incisions were made along the IMF. The remaining 28 (13.7%) incisions were made by other techniques. 201 (98.0%) breasts were immediately reconstructed with tissue expanders (193 went on to implant reconstruction and 8 underwent autologous tissue reconstruction). 4 (2.0%) breasts received delayed reconstruction. Positive margins were found in 15 (7.3%) of 205 breasts. 60 (58.8%) of 102 cancerous breasts that underwent NSM were Stage 0-I, 35 (34.3%) were Stage II and the remaining 8 (7.8%) were Stage III - IV. Complications by case (Table 1) and by breast (Table 2) are shown below. Conclusion: When comparing NSMs in both patients and individual breasts with cancer to patients and breasts treated for prophylaxis, there is no significant difference in complication rates by case or breast, except for the capsular contracture rate, which was significantly higher in breasts treated for cancer. Overall, complication rates are low in both cases of cancer and prophylaxis; this demonstrates that NSM and immediate reconstruction is a highly effective method of treatment for both groups. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-16-03.