tbuckley/cabot-search huggingface dataset:
SP0054 The Many Faces of Mesenchymal Stem Cell Immunomodulation
Authors: F. Djouad
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> Mesenchymal stem cells (MSC) initially isolated in bone marrow have been since identified in other tissues including adipose, synovium, periosteum, perichondrium, dental pulp and tonsil. These cells are characterized by their phenotype and their capacity to differentiate into chondrocytes, osteoblasts and adipocytes. Moreover, MSC potently modulate immune responses, display healing capacities, prevent fibrosis and improve angiogenesis. Taking into account these unique properties, an interest in MSC research has increased over the last decade bringing them into the clinic as a novel therapeutic tool for a variety of autoimmune diseases. The justification to use MSC for the treatment of autoimmune diseases was initially shown in experimental autoimmune encephalomyelitis (EAE). Then, for the treatment of refractory Crohn9s disease the use of autologous bone marrow derived MSC also revealed a significant improvement of the clinical condition of the patients. In patients with systemic lupus erythematosus (SLE) although initial studies using autologous MSC led to unsatisfactory results more recent investigations reported a therapeutic effect of allogeneic MSC. Along with these encouraging results obtained with MSC, their mechanisms of action are still under investigation. Lately, we extensively studied the mechanisms involved in the immunomodulatory properties of MSC both <i>in vitro</i> and <i>in vivo</i>. First, we showed that MSC contribute to the generation of an immunosuppressive environment via the inhibition of proinflammatory T cells and the induction of T cells with a regulatory phenotype. More specifically, we showed that MSC inhibitory effect on the Th17 cell development in favour of the generation of regulatory T cells is mediated by a Gilz-dependent Activin A production. In contrast, on mature Th17 cells we described a cell-to-cell contact depend mechanism mediated through the up-regulation of PD-L1 expression by MSC. <i>In vivo</i>, in a murine model of rheumatoid arthritis (RA) we demonstrated the requirement for Gilz in the therapeutic effect of MSC mediated in part through the generation of regulatory Th17. The suppressive function of MSC confers on them the potential to be used for therapeutic applications in autoimmune diseases. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6248
P271 INTERACTION BETWEEN DIETARY FACTORS AND INSULIN RESISTANCE IN THE PATHOGENESIS OF NONALCOHOLIC STEATOHEPATITIS
Authors: P. Dongiovanni, R. D'Ambrosio, R. Rametta, S. Gatti, M. Maggioni, M. Colombo, S. Fargion, L. Valenti
Journal: Journal of Hepatology (2014)
Abstract 2873: The pandeacetylase inhibitor panobinostat induces the involvement of autophagy related factors in liver cancer cell death
Authors: Pietro Di Fazio, Roberta Montalbano, Karl Quint, Matthias Ocker
Journal: Cancer Research (2011)

Abstract Background. Liver cancer still represents an unmet medical need with rising incidence rates also in Western countries. Panobinostat (LBH589, Novartis Oncology), a pandeacetylase inhibitor, represents a new agent with a promising future in liver cancer therapy. We have previously demonstrated that panobinostat is able to induce cell death in two liver cancer cell lines, HepG2 and Hep3B, through activation of ER stress related apoptotic pathways (Cell Oncol 2010;32:285-300). Panobinostat also significantly reduced the growth of HepG2 xenografts in nu/nu mice. We here demonstrate the implication of autophagy mechanisms into cell demise mediated by panobinostat. Materials and Methods. HepG2 (p53 wt) and Hep3B (p53 null) were treated for 72 hours with panobinostat and cell death was quantified through FACS with propidium ioded staining and CK18 fragmentation staining. Impedance based real-time cell analysis was performed to continuously monitor cell viability after panobinostat treatment. The expression of autophagy related factors was analyzed through RT-qPCR, western blot and immunofluorescence based cytochemistry. Results. Panobinostat induces cell death in a dose and time dependent manner. Autophagy related factors Atg5, Beclin and its activators Ambra, p62 and UVRAG were up-regulated after 48 hours of treatment. We also observed also significant increase of p73 expression in Hep3B cells after 24 hours of treatment. Immunofluorescence based cytochemistry showed a modification of the ubiquitous cytosolic distribution of Beclin and LC3B in both cell lines to a defined spot formation after treatment with panobinostat, indicating a probable autophagosome formation. Western blot analysis also demonstrated an increase of Beclin and LC3-I and LC3-II. Conclusion. Panobinostat treatment determines the involvement of autophagy related mechanisms in a ER stress related apoptosis scenario. The wide spectrum of mechanisms of action of panobinostat need to be further investigated. 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 2873. doi:10.1158/1538-7445.AM2011-2873
P2-08-13: Does Routine Use of Preoperative Magnetic Resonance Imaging (MRI) in Breast Cancer Influence the Outcome?
Authors: R Große, EJ Kantelhardt, S Steer, AK Spinda, M Vetter, K Ruschke, C Thomssen
Journal: Cancer Research (2011)

Abstract Introduction: The role of routine preoperative breast MRI in patients diagnosed with breast cancer is still under discussion. In a milestone review, Houssami et al. (CA Cancer J Clin 2009;59;290) did not demonstrate an advantage with regard to DFS or OS. We reviewed our case series (n=793) in order to add evidence to the current discussion of whether or not preoperative MRI would influence the outcome. Material and Methods: In our database we identified four years of diagnosis (2004-07) in which a high percentage (72%) of patients (349 of 483) with histologically confirmed invasive breast cancer received preoperative MRI. In the following years (2008/09), MRI was still done in 31% of the cases (97 of 309). All pts were treated according to national guidelines; however, patients with additional lesions in MRI were subjected to an additional MRI-guided needle biopsy or additional wire-guided excision. The median follow-up time was 31.5 months (0-81). The patients were followed clinically. In most cases local surveillance was done by mammography. Results: In the total cohort, 20% of the patients had additional needle biopsies and/or wire-localisation due to MRI-findings. By MRI, lesions that subsequently led to an additional preoperative needle biopsy were found in 82 pts. Interestingly, only ten contralateral second cancers were found. In 357 pts, MRI was used as guidance during the operation with (n=118) or without MRI-supported wire localization (n=238). The percentage of additional MRI-needle biopsy or MRI-supported localisation did not differ between invasive ductal (n=655) and lobular cancer (n=91): 10% versus 13% needle biopsies and 15% versus 20% wire localisations. The number of surgical procedures to achieve tumor-free margins did not differ between patients with or without preoperative MRI. In this series, 69 of 100 patients who received neoadjuvant chemotherapy, also had MRI-imaging. Considering the patient cohort with follow-up available (n=737), no significant difference of DFS probability was observed between pts with and without preoperative MRI. Discussion: This retrospective analysis did not demonstrate any advantage for routine preoperative MRI with regard to local treatment and DFS probability. The observed rate of 20% additional operative procedures corresponds to similar published data (16% additional multicentric or multifocal lesions found by MRI, Solin, Breast. 2010;19:7). Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-08-13.
Abstract 5400: Antiangiogenic gene therapy with VB111 is active in glioblastoma xenografts
Authors: Andrew J. Brenner, Jessica Rogge, Yael Cohen, Eyal Breitbart, Bangio Livnat
Journal: Cancer Research (2011)

Abstract Introduction: Glioblastoma is a highly vascular tumor with marked endothelial dependence. While anti-angiogenic therapy has shown transient clinical benefit for the treatment of glioblastoma, persistent vascularization is seen with a normalization of blood vessels within the tumor. VB-111 is a dual-action, anti-angiogenic and vascular disrupting agent for cancer treatment aimed specifically at destroying newly formed and existing tumor blood vessels in a safe and efficient manner. VB-111 consists of a replication incompetent adenovirus together with an endothelial angiogenic-specific promoter and a pro-apoptotic Fas chimera transgene. Methods: Intracranial xenografts were established in nude rats with a luciferase expressing U87 glioma cell line. Rats were treated intravenously with VB-111 at 1011 viral particles or placebo at 21 days post tumor cell implantation. Tumor growth was followed by in vivo bioluminescent imaging and 7T MRI. Rats were sacrificed when moribund or when marked neurologic deficit was observed. Tumors were evaluated by standard histologic methods for vessel density and necrosis. Results: Untreated rats bearing U87 tumors showed a median survival of 38 days (95% CI 35.1-40.9 days), while animals treated with VB-111 showed a median survival of 48 days (95% CI 42.1-53.9 days). Log rank analysis of survival distributions between these two groups showed a significant difference (p=0.024) in favor of treatment. Luciferase activity, used as a surrogate for tumor volume, began separating between the two groups in week two post treatment and showed a continued trend for reduced activity in the treatment group thereafter. MRI imaging confirmed decreased tumor size in representative animals from the VB-111 group. Conclusions: VB-111's Dual action therapy is promising for glioblastoma. 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 5400. doi:10.1158/1538-7445.AM2011-5400
632 RECOMBINANT HCV VIRUS LIKE PARTICLES TO INDUCE HUMORAL AND NEUTRALISING ANTIBODY RESPONSES TO HCV
Authors: R. Chin, L. Earnest-Silveira, B. Koeberlein, D. Johnson, D. Johnson, S. Franz, H. Zentgraf, D.C. Jackson, C.-T. Bock, J. Torresi
Journal: Journal of Hepatology (2008)
FAVORABLE EFFECTS OF IVABRADINE ON SYMPATHETIC OVERDRIVE AND ARTERIAL STIFFENING IN HYPERTENSIVE PATIENTS WITH METABOLIC SYNDROME
Authors: Konstantinos P. Tsioufis, Kyriakos Dimitriadis, Theodoros Kalos, Eirini Andrikou, Panagiotis Vasileiou, Anastasios Milkas, Ioannis Andrikou, Alexandros Kasiakogias, Costas Thomopoulos, Dimitris Tousoulis
Journal: Journal of the American College of Cardiology (2016)
P4-16-08: Pilot Randomized Trial of De-Escalated (q12 Weekly) Versus Standard (q3-4 Weekly) Intravenous Bisphosphonates in Women with Low-Risk Bone Metastases from Breast Cancer.
Authors: E Amir, O Freedman, L Carlsson, T Usmani, E Lee, G Dranitsaris, M Clemons
Journal: Cancer Research (2011)

Abstract Background: Bone-targeted agent such as bisphosphonates (BPs) can reduce skeletal complications from bone metastases but have no effect on either disease progression or survival. Despite substantial variability in the frequency and severity of skeletal complications, patients are empirically treated with BPs at the same dose and schedule irrespective of their individual risk. Materials and Methods: A pilot, randomized, non-inferiority trial was conducted. Patients with low-risk bone metastases (serum C-telopeptide [CTx] &amp;lt;600ng/L after at least 3 cycles of monthly IV BP) were assigned to pamidronate 90mg IV either every 3–4 weeks (control) or every 12 weeks (de-escalated). Data on serum CTx and bone alkaline phosphatase (BAP), pain scores (brief pain inventory [BPI] and functional assessment of cancer therapy-bone pain [FACT-BP]) were collected at 12 weekly intervals for 48 weeks. Results: Fifty-four patients were approached, 44 provided consent and 38 were eligible for randomization. Median age was 55 (range 29–77) and mean baseline CTx was 319ng/L (range 10–526). Thirty-five participants (92%) completed the trial, 2 withdrew consent and one participant died. Fourteen control group participants (73.7%) and 13 experimental group participants (68.4%) maintained CTx in the low risk range (test for two proportions p=0.64). All patients not maintaining CTx in the low risk range showed evidence of both visceral and bone progression. Compared to the control group, there was a trend towards increasing CTx with time in the experimental group (p=0.10). There was no significant difference in BAP (p=0.37), BPI (p=0.21) or FACT-BP scores (p=0.59) between the two groups. Over the 48 week follow-up, two skeletal events were observed in each group. Conclusions: Randomized trials of de-escalated BP therapy in women with low-risk bone metastases are feasible. Twelve-weekly pamidronate appears non-inferior to 3–4 weekly treatment. Larger trials are required to assess whether; 1) increasing CTx levels with de-escalated therapy will lead to higher rates of skeletal complications and 2) whether BP should be given every 3–4 weeks in patients with progressive visceral and bone disease. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-16-08.
SAT0107 Antinuclear Antibody Positivity in RA Patients and Its Impact on Persistency of TNF Inhibitors
Authors: Y.-K. Sung, S.-K. Cho, D. Kim, S. Won, J.I. Choi, C.-B. Choi, T.-H. Kim, J.-B. Jun, D.-H. Yoo, S.-C. Bae
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Recently, it was reported that the antinuclear antibody (ANA) before starting anti-TNF treatment or development of ANA might be related with clinical response of TNF inhibitors or side effect of infusion reactions. <h3>Objectives</h3> The aims of this study were to examine the prevalence of positive ANA before starting TNF inhibitors in patients with RA and to investigate the impact of ANA positivity on persistency of anti-TNF treatment. <h3>Methods</h3> Among 355 RA patients who started their first TNF inhibitor between 2000 and 2011, 273 patients who had performed ANA test before starting anti-TNF treatmentwere identified in theretrospective biologics registry in Korea of REtrospective study for Safety and Effectiveness of anti-RA treatment with biologiCs (RESEARCh). We classified all patients into two groups according topositivity of ANA; positive group (ANAtitres at a dilution ≥1:160) and negativegroup (ANAtitres &lt;1:160). The period of observation for evaluating drug survival was defined as the time between starting of TNF inhibitors and their discontinuation or their last study visit if they continued therapy. Kaplan-Meier survival analysis was used to assess persistence, log-rank tests were used to compare drug survival between ANA positive and negative groups, and Cox proportional hazards models were used to assess whether ANA positivity is a potential predictor of treatment discontinuation. <h3>Results</h3> Among 273 RA patients (mean age of 47.9 years and 85% of female), 131 (48%) patients were ANA positive before starting TNF inhibitors. At the baseline, ANA positive group was more commonly positive with rheumatoid factor (80% vs. 65%, p&lt;0.01) and had higher disease activity with DAS 28 (6.2±0.9 vs. 5.9±0.9, p&lt;0.01) compared to ANA negative group, while other potential predictors were comparable between two groups. In both groups, there was no significant difference in drug discontinuation rates due to all causes (P=0.97), side effects (p=0.83), and non-effectiveness (p=0.67). Cox-proportional hazards models showed that ANA positivity was not a risk factor for discontinuation due to all causes (OR 1.02, CI 0.63-1.65), side effects (OR 1.00, CI 0.98, 1.02), and non-effectiveness (OR 1.00, CI 0.97, 1.02). <h3>Conclusions</h3> The prevalence of ANA positivity in RA patients who started TNF inhibitors were 48% and ANA positive patients had higher disease activity and RF positivity compared to ANA negative RA patients. However, ANA positivity was not associated with TNF inhibitor discontinuation due to overall causes, side effects, and non-effectiveness. <h3>Acknowledgements</h3> This study was supported by a grant of the Korea Healthcare technology R&amp;D Project, Ministry of Health and Welfare, Republic of Korea.(HI10C2020). <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4129
AB0008 Familial mediterranean fever (FMF) gene mutations (MEFV): are they a risk factor for coronary artery disease?
Authors: B. Kisacik, N. Basar, S. Ercan, Y. Pehlivan, S. Yilmaz, I. Simsek, H. Erdem, O. Ozer, S. Pay, A. Dinc, A.M. Onat
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Familial Mediterranean fever (FMF) is an autosomal recessive disease which predominantly affects certain ethnic groups mainly Sephardic Jews, Turks, Arabs and Armenians. The gene causing FMF, designated MEFV, encodes a protein called pyrin or marenostrin that is expressed mainly in myeloid bone marrow precursors, neutrophils, and monocytes. <h3>Objectives</h3> Cardiovascular diseases (CVD) are very common in general population. The prevalence of coronary heart disease (CHD) is approximately one-third of total CVD. Atherosclerosis is responsible for main pathogenesis. Circulating inflammation markers may be correlated with atherosclerosis such as high-sensitivity C-reactive protein and homocysteine. Familial Mediterranean fever (FMF) is an autosomal recessive disease which predominantly affects certain ethnic groups mainly Sephardic Jews, Turks, Arabs and Armenians. The gene causing FMF, designated MEFV, encodes a protein called pyrin or marenostrin that is expressed mainly in myeloid bone marrow precursors, neutrophils, and monocytes. We herein aimed to determine the prevalence of MEFV mutations (all exon 2, 10 mutations) in early coronary heart disease (early CHD) and coronary heart disease (CHD) with multiple risk factors and healthy control population. <h3>Methods</h3> The study population consists of three groups. Group 1 was consist of 91 patients with early CHD at &lt;45 years of age for men, &lt;40 years of age for women (male/female: 83/8), group 2 on the other hand included 106 patients with CHD at &gt;50 years of age (male/female: 77/29) and finally in group 3, 119 healthy controls involved into study (male/female: 111/8). <h3>Results</h3> None of patients was diagnosed with FMF. 38 patients (41.8%) with early CVD, 17 patients (16%) with CVD, 24 healthy control (20.2%) carried at least one mutated MEFV allele. Young patients with CHD have different risk factor profiles, clinical presentations, and prognoses than older patients. Young patients with CHD usually have multiple risk factors. <h3>Conclusions</h3> This study suggests that MEFV mutations with early CHD patients had significantly increased in contrast to CHD patients and healthy controls. <h3>Disclosure of Interest</h3> None Declared
723 RISK ASSESSMENT OF LIVER-RELATED EVENTS DEVELOPMENT USING TRANSIENT ELASTOGRAPHY IN PATIENTS WITH CHRONIC HEPATITIS B RECEIVING ENTECAVIR
Authors: M.N. Kim, S.U. Kim, J.Y. Park, D.Y. Kim, K.-H. Han, C.Y. Chon, S.H. Ahn
Journal: Journal of Hepatology (2013)
Treatment of Disseminated Germ-Cell Tumors with Cisplatin, Bleomycin, and either Vinblastine or Etoposide
Authors: Stephen D. Williams, Robert Birch, Lawrence H. Einhorn, Linda Irwin, F. Anthony Greco, Patrick J. Loehrer
Journal: New England Journal of Medicine (1987)

Standard chemotherapy for disseminated germ-cell tumors includes a combination of cisplatin, vinblastine, and bleomycin, but this regimen produces substantial neuromuscular toxicity. In a randomized clinical trial in 261 men with disseminated germ-cell tumors, we substituted etoposide for the vinblastine in this regimen in half the patients to compare the efficacy and toxicity of the two treatments. Among 244 patients who could be evaluated for a response, 74 percent of those receiving the regimen including vinblastine and 83 percent of those receiving the regimen including etoposide became disease-free with or without subsequent surgery (P not significant). Among the 157 patients with high tumor volume, 61 percent became disease-free on the regimen that included vinblastine, as compared with 77 percent on the regimen that included etoposide (P less than 0.05). Survival among the patients who received etoposide was higher (P = 0.048). The regimens were similar in terms of myelosuppressive effects and pulmonary toxicity. However, the etoposide regimen caused substantially fewer paresthesias (P = 0.02), abdominal cramps (P = 0.0008), and myalgias (P = 0.00002). We conclude that etoposide with cisplatin and bleomycin is superior to vinblastine with cisplatin and bleomycin in the treatment of disseminated germ-cell tumors because of diminished neuromuscular toxicity and, among patients with advanced disease, better efficacy.
Differences in outcome of young breast cancer patients according to BRCA1 mutation status.
Authors: D Gabrys, K Trela, A Boratyn-Nowicka, R Suwinski, E Grzybowska, K Behrendt, K Galwas, P Wojcieszek, A Idasiak, H Thames
Journal: Cancer Research (2009)

Abstract Abstract #1044 Introduction&amp;#x2028; 5 to 10 % of all breast cancer and 25 % of early onset breast cancer are inheritable, which may be caused by mutations of tumour suppressor genes such as BRCA1. Moreover, the issue of a familial breast cancer has raised much attention in recent years due to numerous medical and social implications. In the present paper we investigate the clinical characteristic and outcomes of younger (&amp;lt;50 years old) breast cancer patients with BRCA1 mutation in comparison to patients without this germline mutation.&amp;#x2028; Methods and Materials&amp;#x2028; This is an ongoing study and patients will be enrolled till end of 2008. Till now we followed 495 breast cancer patients who were diagnosed before age 50 and were asked to provide a blood sample for BRCA1 mutation screening. We compared contralateral breast cancer and ovarian cancer incidence, disease free, metastases free, and overall survival, between BRCA1 mutation carriers and non-carriers.&amp;#x2028; Results&amp;#x2028; BRCA1 mutations were detected in 90 breast cancer patients (5382insC in 60 patients, 300T/G in 18 pts, 185delAG in 10 pts, and 4153delAin 2 pts); the remaining 405 women did not carry the mutation. BRCA1 related tumours showed higher grade, higher Ki67 protein expression, more frequent negative oestrogen, progesterone, HER2-neu receptor status. Patients with BRCA1 mutation had a higher incidence of bilateral breast (40% compared to 10% in non mutated patients) and ovarian cancer (16% compared to less than 1% in non mutated patients. 10-years OS (overall survial) was 81% in no BRCA1 mutation patients compare to 88% in mutated BRCA1 patients (p=0.7), 10-years DSF (local-regional and distant failure) was 81% vs. 67% (p=0.8), 10-years MFS (metastases free survival) was 85% vs 71% (p=0.1), and 10-years RFS (recurrence free survival) was 90% vs. 80% (p=0.1) respectively.&amp;#x2028; Multivariate Cox analysis for DFS showed that node ratio &amp;gt; 12% (HR=2.12), increasing tumour diameter (HR=1.23), experienced significantly decreased DFS. Furthermore, overall survival analysis also showed that node ratio &amp;gt; 12% (HR=2.65), increasing tumour diameter (HR=1.23), experienced significantly decreased OS. There is an insignificant trend for patients without BRCA1 mutation and younger to have worse DFS (HR=1.28) and worse OS (HR=2.23).&amp;#x2028; Conclusions&amp;#x2028; Patients with BRCA1 mutations have higher incidence of bilateral breast and ovarian cancer which imposes the need for frequent and careful follow-up after therapy. Node ratio and tumour diameter are the strongest prognostic factors. A final conclusion will require more patients and longer follow up. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1044.