tbuckley/cabot-search huggingface dataset:
AB0212 Decreased Serum Vitronectin Level in Systemic Sclerosis: Table 1.
Authors: B. Gundogdu, S. Yolbas, A. Yildirim, S. Aydin, S.S. Koca
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Vitronectin, one of the integrin αvβ3 ligands, is a multifunctional glycoprotein that is present in blood and in the extracellular matrix. Decreased levels of vitronectin have been reported in patients with meningococcal disease, rheumatoid arthritis and Behçet9s disease. <h3>Objectives</h3> The aim of the present study was to evaluate serum vitronectin level in systemic sclerosis (SSc) and systemic lupus erythematosus (SLE). <h3>Methods</h3> 86 patients with SSc and 46 patients with SLE and 38 healthy volunteers (HC) were included in the study. Serum IL-6, TGF-β and vitronectin levels were analyzed by ELISA method. <h3>Results</h3> The level of vitronectin was lower in the SSc group compared to the SLE and HC groups (p&lt;0.001 for both), while its level was similar in the SLE and HC groups (Table). Although vitronectin level was not different between the diffuse and limited cutaneous subtypes of SSc (p=0.390), its level was negatively correlated with modified Rodnan skin score (r=-0.256, p=0.016). Serum vitronectin level was negatively correlated with visual analogue scales (physician and patient), lung-Medsger and heart-Medsger scores, too (r=-0.450, p&lt;0.001; r=-0.321, p=0.003; r=-0.319, p=0.003 and r=-0.245, p=0.023, respectively). Sex, the positivity of anti-sentromer and anti-Scl-70 antibodies, and the presences of pulmonary fibrosis, pulmonary arterial hypertension and digital ulcer were not altering the serum vitronectin level. <h3>Conclusions</h3> Serum vitronectin level decreases in SSc in contrast to SLE. Fibrosis is the main difference of SSc from SLE. Therefore, it may be concluded that the one cause of decreased serum vitronectin level in SSc may be fibrogenesis. It has been demonstrated previously that vitronectin accumulates in fibrotic area in an experimental model of renal fibrosis. Moreover, the negative correlation between serum vitronectin level and modified Rodnan skin score support this conclusion. <h3>References</h3> Schvartz I, et al. Int J Biochem Cell Biol. 1999;31(5):539-44. Høgåsen K, et al. Infect Immun. 1994;62(11):4874-80. Horton MA. Int J Biochem Cell Biol. 1997;29(5):721-5. Wilder RL. Ann Rheum Dis. 2002;61(Suppl 2):i96-9. Koca SS, et al. Rheumatol Int. 2013 Dec 28. [Epub ahead of print] Lόpez-Guisa JM, et al. Am J Physiol Renal Physiol. 201;300(5):F1244-54. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4856
High-Alcohol Mouthwashes Are Under Scrutiny
Authors: K. Smigel
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article High-Alcohol Mouthwashes Are Under Scrutiny Get access Kara Smigel Kara Smigel Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 11, 5 June 1991, Page 751, https://doi.org/10.1093/jnci/83.11.751 Published: 05 June 1991
SAT0502 Comparison between Oral or Intra-Articular Corticoids in the Management of Acute Gout Flare in Patients with Chronic Renal Failure
Authors: C.A. Guillen Astete, A. Boteanu, A. Zea
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Chronic renal failure is a condition that limits the use of non steroidal anti-inflammatory drugs (NSAIDs) or colchicine. Both therapies should be used cautiously or avoided, and in its place many clinicians use glucocorticoids. Although it is a therapy commonly used worldwide, there are no clinical assays sustaining the superiority of intra articular glucocorticoids over oral administration. The aim of present study is to compare benefits of both therapies in terms of symptoms control. <h3>Objectives</h3> The aim of present study is to compare benefits of both therapies in terms of symptoms control. <h3>Methods</h3> Clinical charts of patients with chronic renal failure with a single joint flare of gout were reviewed. Only patients treated with glucorticoids (oral or intra articular) and who did not receive NSAIDs nor colchicine was included. Epidemiologic variables were analyzed and the effectiveness of both therapies (oral or intra articular glucocorticoids) was compared in terms of symptoms relief and time until resolution. All the data were obtained directly from the informatic archives and clinical charts of each patient. Resultd were grouped acoording to the way of glucocorticoid administration. <h3>Results</h3> From 101 gout treatments selected, 69 (68.3%) were enough documented for the purposes of the study. Forty five patients (44.5%) were treated with joint injection of 20 to 40mg of triamcinolone (group I) and the rest received oral prednisone at a rate of 0.1-0.2 mg/kg/d (group II) or 0.2-0.3 mg/kg/d (group III). The proportion of patients treated also with opioids or who received a first intravenous corticoid dose was similar among the three groups treated orally with glucocorticoids. Therapeutic success was reached at day 15 in 75.5%, 62.5%, 75.0% and 75.0% of patients from groups I, II and III, respectively (p&gt;0.05). No differences into the rate of local or systemic infections, hypertensive crisis or hyperglycemic status were detected among the three groups. The survival curve (symptoms relief) did not show differences accelerating or slowing the response variable according to any group of treatment (Coeff -0.1805 E.E. 0.1048 HR 0.8348 p 0.08). <h3>Conclusions</h3> Our data do not support any superiority of the use of these different ways of glucocorticoids administration in a single joint gout flare in patients with chronic renal failure. In terms of relief of symptoms and security profile both strategies are similar. We conclude that both therapies could be used indistincly however larger studies should be performed in order to make posible important stratifications such as time of glucocorticoids administration, cumulative dosis, other therapies administered simultaneously or the joint affected. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3943
Abstract 5414: AMPK regulates HER2/EGFR activity in HER2-positive breast cancer.
Authors: Teraneh Jhaveri, Ju Hyung Woo, Edward Gabrielson
Journal: Cancer Research (2013)

Abstract The AMP-activated Protein Kinase (AMPK) is a master regulator of cell metabolism, controlling fatty acid synthesis, protein synthesis and carbohydrate metabolism. Physiological states with increased AMPK activity are associated with decreased cancer incidence, leading to interest in AMPK as a potential target for cancer therapy and prevention. To explore a possible role of AMPK modulation in breast cancer therapy, we investigated how activation of AMPK affects breast cancer cell signaling and survival. Initial experiments found that breast cancer cell lines with amplification and over-expression of HER2 (BT474, HCC1419, and SKBR3) are 2-fold to 5-fold more sensitive to cytotoxic effects of AICAR, a canonical pharmacological activator of AMPK, than breast cancer cell lines that lack HER2 amplification (MCF7 and MDA231). In parallel to this activation of AMPK, we observed dose- and time-dependent inhibitory effects on phosphorylation and activity of HER2 and EGFR in these AICAR-treated, HER2-amplified breast cancer cells, with activation of AMPK and suppression of HER2/ EGFR activity preceding commitment to cell death. To further explore how AMPK activity affects HER2/ EGFR, we stably transfected HER2-amplified breast cancer cells with constitutively active AMPKα and observed that AMPK activated by this genetic manipulation also leads to decreased HER2 and EGFR phosphorylation and associated downstream signaling as well as reduced cell growth. Finally, we found that morin, a flavinoid compound previously found to inhibit fatty acid synthesis, also activates AMPK and inhibits HER2 and EGFR signaling in parallel, further supporting the link across these pathways. Our results lead us to postulate that AMPK regulates HER2 and EGFR activity in HER2-amplified breast cancer cells, and activation of AMPK might provide therapeutic benefit in such cancers. Citation Format: Teraneh Jhaveri, Ju Hyung Woo, Edward Gabrielson. AMPK regulates HER2/EGFR activity in HER2-positive breast cancer. [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 5414. doi:10.1158/1538-7445.AM2013-5414
SP0027 Biosimilars: Potential Clinical Differences and European Regulatory Aspects
Authors: J.V. Esplugues Mota
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> Although successful drugs, the use of anti-TNFs is limited by their high cost, and in the present climate of economic difficulty, there is pressure to find alternatives that reproduce their effects at a lower price. Due to their large molecular size and structural complexity, anti-TNFs are impossible to duplicate, unlike smaller, chemically-generated compounds, which can be copied. However, unlike generics, biosimilars are similar rather than identical to the original drugs. Determining the level of similarity that guarantees a comparable efficacy and safety represents a new test for the pharmacological market. Biosimilars of smaller biological molecules, such as somatotropin, EPO and GCSF (granulocyte colony-stimulating factor), are already commercially available, but are less of a challenge than anti-TNF a biosimilars, which are 3-4 times larger. The European Medicines Agency has recently approved the first infliximab biosimilar, which has already been marketed in various European countries with all the indications for which the original product was approved. However, last January, the Canadian Agency for Drug and Technologies in Health ruled out the use of this biosimilar to treat inflammatory bowel disease in adult and paediatric patients. The fact that two such important regulatory agencies have published contrasting rulings based on the same data is testimony to the complexity of these large protein molecules. Indeed, the novel pharmacology of biosimilars has forced regulatory authorities to develop specific guidelines for their development. European regulations require manufacturers to validate the synthesis process through which they create biosimilars, since the process employed to create the original drug cannot be reproduced. In addition, they are required, not only to carry out pharmacokinetic studies, but also to compare biosimilars with the original product in phase I and II clinical trials. In the case of the infliximab biosimilar, its approval has been achieved through two clinical trials involving a total of 860 patients; a therapeutic equivalence study with rheumatoid arthritis subjects and a pharmacokinetic study with ankylosing spondylitis subjects. No significant differences were detected with respect to infliximab in either study. Specific immunogenicity studies are also required, as well as a specific pharmacovigilance plan that should continue for some time after the drug is made commercially available. This caution is merited by the potential antigenicity of biosimilar proteins, and is of particular relevance in the case of infliximab, which has the most antigenic profile of all the anti-TNFs currently on the market. Given that the infliximab biosimilar is the first of its class, only time will tell whether it can influence the treatment of rheumatologic diseases, in which infliximab is not currently a first-line option. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6337
Abstract 1393: Chitinase-3-like-1 protein overexpression in lung epithelial cells enhances breast cancer metastasis to the lung
Authors: Stephania Libreros, Ramon Garcia-Areas, Lilllian Onwuha-Ekpete, Vijaya Iragavarapu-Charyulu
Journal: Cancer Research (2012)

Abstract Breast cancer is the most common cancer in women in the US. Metastasis is responsible for a majority of these deaths in spite of significant improvements in diagnosis and treatments. Recently it was reported that under conditions of asthma, metastasis to the lung is increased. Patients with pulmonary inflammatory illnesses demonstrate higher levels of chitinase-3-like-1 protein (CHI3L1) in their lungs and in circulation. We have shown that there are elevated levels of CHI3L1 in circulation with increased tumor growth, higher levels of metastasis to the lung with shorter survival rates in mice with asthma. However, the direct role of CHI3L1 in promoting metastasis is not clearly delineated. It is also unknown if exposure to high levels of CHI3L1 previous to tumorigenesis directly predisposes to accelerated metastasis. We hypothesize that CHI3L1-induced pulmonary inflammation generates the proper environment for recruiting circulating breast cancer cells, thus increasing the rate of metastasis to the lung. To determine if inflammation associated with CHI3L1 in the lung alters the pulmonary environment to attract circulating breast tumor cells and accelerate metastatic growth, pulmonary inflammation is induced by either ragweed allergen sensitization or by locally expressing CHI3L1 in the lung using AAV-CC10-CHI3L1 vector. The role of CHI3L1 in pulmonary metastasis is delineated in CHI3L1 over-expressing lung epithelia by assessing the effects on the host immune system and the downstream effects. The studies proposed here will provide a greater understanding of the role of CHI3L1 in enhancing metastasis and the tissue-specific molecular signals that act to exacerbate metastasis under conditions of chronic inflammation 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 1393. doi:1538-7445.AM2012-1393
THU0196 Disease Course after the Permanent Cessation of Biological Therapy in Inflammatory Rheumatic Diseases
Authors: G. Kádár, B. Soós, A. Laduver, P. Keszthelyi, Z. Szekanecz, L. Kovács
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> Currently there are no guidelines regarding the possibility and the timing of the discontinuation of biological therapy in patients with sustained remission. The authors' aim was to assess the disease course after permanent stopping of the biologics in three Hungarian arthritis centres. <h3>Methods</h3> In this retrospective, multicenter cohorts study, 126 patients with rheumatoid arthritis (RA) (average age: 60 years), 38 patients with ankylosing spondylitis (AS) (average age: 50 years) and 11 patients with psoriatic arthritis (average age: 54 years) were enrolled in whom biological therapy had permanently been stopped because of several reasons. Data on the reason of cessation of biological therapy, and on the subsequent disease course were collected. <h3>Results</h3> The reasons of stopping the biological therapy were: side effect (6,8%), allergic reaction (11,4 %), infections (14,2 %), tumor appearance or tumor search (12 %), permanent remission (10,2 %), family planning (4 %), ineffectivity (16 %), poor compliance (15,4 %), and other reasons (9,7 %). When the biological therapy was stopped, RA disease activity was low in 38,8 % of the patients (DAS-28&lt; 3,2), and high in 19 % (DAS-28 &gt;5,1). In AS, 13,1 % of the patients had low (BASDAI &lt; 2,0), whereas 44,7 % had high activity (BASDAI &gt; 4,1). After an average of 22 months, 37 % of the RA patients remained in remission, and 22 % had high disease activity. In AS, an average of 19 months 17,6 % of the patients had low disease activity., and 52,9 % had high. 55,5 % of the RA patients took synthetic DMARDs, and 27,7 % corticosteroids after the withdrawal of biologics. During the follow-up relapse occured in 31 % of the RA, and 37 % of the AS patients. The duration of biological therapy and low disease activity at cessation predicted a sustained biologic-free remission. <h3>Conclusions</h3> After permanently stopping the biological therapy, considerable proportion of RA patients may remain in sustained remission, whereas the likelihood of long-term low disease activity is lower in AS patients. Identification of predictors of a sustained biologic-free remission should be of high priority. <h3>Disclosure of Interest</h3> None Declared
1150 A COMPREHENSIVE REVIEW OF PATTERNS OF VIRAL LOAD DECLINE IN PATIENTS TREATED WITH TELAPREVIR PLUS PEGINTERFERON AND RIBAVIRIN
Authors: G. Picchio, S. De Meyer, I. Dierynck, A. Ghys, L. Gritz, T.L. Kieffer, D.J. Bartels, F. Tomaka, L. Bengtsson, D. Luo, I.M. Jacobson, R.S. Kauffman, N. Adda, C. Sarrazin
Journal: Journal of Hepatology (2012)
Clinical outcomes of patients with T1N0 breast cancers: how important are biological risk factors?.
Authors: RH De Boer, A Chan
Journal: Cancer Research (2009)

Abstract Abstract #2078 Background: Tumour size (T) and nodal status (N) have traditionally been regarded as the most important prognostic factors which determine individual recommendations for adjuvant treatment. Early trials of adjuvant systemic therapy relied on nodal status as the key determinant of recurrence risk, with node negative patients (pts) often excluded due to their 'low risk' classification. With greater understanding that predominant growth signalling pathways in a given tumour may be of greater importance than size and nodal spread, current clinical practice places greater emphasis on high risk biological factors. Factors include young age (&amp;lt;35y), HER2 positivity (pos), grade III status, absence of hormone receptors (HR), and triple negative (TN) phenotype. Presence of these features will likely influence systemic treatment recommendations. With this in mind we examined data which has been prospectively collected to determine the outcomes of pts with high risk T1N0 tumours and compared them to pts with lower risk biological profiles.&amp;#x2028; Methods: Data on 2285 pts with early breast cancer were analysed. Comparisons were made between T1N0 high risk pts (defined as having one or more of the following features: age&amp;lt;35, grade III, HER2 pos, or TN) and pts with good biological prognostic features (defined as the absence of all the above factors) in the following subgroups: 1) T1N0, 2) T1N1-2, and 3) T2-3N0. In addition outcomes were specifically assessed in T1N0 pts with Her2 pos vs negative disease; TN vs non-TN.&amp;#x2028; Results: 401 pts with T1N0 high risk tumours were identified (T1N0HR). In the low risk group there were 330 pts with T0 tumours (T1N0LR), 286 pts with T1Npositive tumours (T1NposLR) and 154 pts with T2/T3N0 tumours (T2/3N0LR). There were 137 pts T1N0 Her2 pos (T1N0H2). The median follow up for all pts was 3.4 yrs (0.5-36). Treatment given and clinical outcome for each pt group are shown in the table.&amp;#x2028; &amp;#x2028; The majority of DFS events in the T1N0H2 pts occurred in those not receiving adjuvant trastuzumab (12.4% vs 2.2%). TN tumours were seen in 12.5% of pts studied. Despite the use of systemic therapy in 97.5% of TN pts (vs 64% in non-TN) , there was a higher DFS event and death rate (18% vs 15%; and 13% vs 6% respectively)&amp;#x2028; Conclusions: Outcomes for T1N0HR pts were similar to that of T1N0LR and T2/3N0LR pts, possibly related to the greater use of systemic therapies in the T1N0HR pts (89% vs 50% vs 79%). Despite the high rate of adjuvant systemic therapy, the outcomes for the T1N0HR group were inferior to the outcomes for pts in the T1NposLR group (DFS 15.7% vs 9.8%) supporting the view that biological factors may be a more important determinant of outcome than nodal status. Similarly, even in pts with small tumour size, triple negative phenotype had worse outcome. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2078.
Reduced Mortality among Children in Southern India Receiving a Small Weekly Dose of Vitamin A
Authors: Laxmi Rahmathullah, Barbara A. Underwood, Ravilla D. Thulasiraj, Roy C. Milton, Kala Ramaswamy, Raheem Rahmathullah, Ganeesh Babu
Journal: New England Journal of Medicine (1990)

Clinical vitamin A deficiency affects millions of children worldwide, and subclinical deficiency is even more common. Supplemental vitamin A has been reported to reduce mortality among these children, but the results have been questioned.
Abstract 1551: Soluble tissue transglutaminase modulates cellular adhesion to matrix and peritoneal metastasis in ovarian cancer
Authors: Bakhtiyor Yakubov, Bhadrani Chelladurai, John Turchi, Daniela E. Matei
Journal: Cancer Research (2011)

Abstract Background: Tissue transglutaminase (TG2) is a secreted protein that binds fibronectin (FN) and exerts protein transamidating activity in the presence of Ca2+. We previously reported that TG2 is upregulated in ovarian cancer (OC) cells and enhances intraperitoneal (ip) metastasis. TG2 is secreted abundantly in OC ascites, yet the function of soluble (s) TG2 remains unknown. We hypothesized that sTG2 acts as a permissive factor in the ECM by promoting cancer cell proliferation and adhesion to the matrix. Materials and Methods: Recombinant his6-tagged full length human TG2 and its inactive enzymatic mutant C277S were purified by immobilized metal (Co2+) affinity and anion exchange chromatography. OV90 and A2780 OC cells that do not express endogenous TG2 were used. Solid phase adhesion assay measured adhesion to ECM proteins, MTT assay measured cell proliferation and an ip xenograft model quantified tumor formation and metastasis. Results: S-TG2 enhanced cell adhesion to FN (p = 0.01) and vitronectin (VN, p = 0.01), but not to collagen and laminin. A neutralizing antibody to α5β1 and to αVβ3 blocked sTG2 induced cell adhesion to FN or to VN, respectively, suggesting that sTG2 modulates cell interaction with the matrix via integrins. Digestion of FN with matrix metallo-proteinase 2 blocked OC cell adhesion to digested fragments of FN, while addition of sTG2 restored OC cells’ binding to this protease-digested matrix (p = 0.02). This suggests that the soluble enzyme may facilitate the interaction of OC cells with a protease-remodeled matrix remodeled, similar to the tumor ECM. Enzymatically inactive soluble C277S TG2 enhanced OC cell adhesion to FN to the same extent as wild type TG2. In contrast, an antibody raised against the FN-binding domain of TG2 blocked sTG2 induced OC cell adhesion to FN (p =0.01). These data suggest that the interaction between TG2 and FN, but not the transamidating activity, is important to sTG2-mediated cell interaction with the ECM. When added to conditioned media, sTG2 (2.5ug/mL) increased OC cell proliferation by 20% (p = 0.01). Biweekly ip inoculation of 2.5ug sTG2 increased peritoneal dissemination of OV90 cells in nude mice (11.38 vs. 27.75, p = 0.02), but did not affect tumor volume (412.3 vs. 578.2 mm3, p = 0.34). Conclusions: These data demonstrate that sTG2 increases OC cell adhesion to the ECM and peritoneal metastasis. The key mechanism involved in this process is the interaction between sTG2, FN, and integrins. 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 1551. doi:10.1158/1538-7445.AM2011-1551