tbuckley/cabot-search huggingface dataset:
Abstract #3896: Growth inhibition of human lung cancer cells by Cucurbitacin B: potential mechanisms
Authors: Hina Kausar, Radha Munagala, Ramesh Gupta
Journal: Cancer Research (2009)

Lung cancer is the most common cause of cancer mortality worldwide, with over 1.3 million deaths and continues to be a major health problem. Chemotherapeutic, radiation and surgical interventions have produced slight declines in mortality rates in recent years; however, it appears unlikely that additional marked improvements with these practices alone will occur in the near future. This grim overview urges powerfully for new, emerging approaches such as molecular or biologically targeted therapies and chemoprevention for the control of lung cancer. Over the recent years plant derived phytochemicals have gained increasing importance for their potential cancer chemopreventive and therapeutic activities. In this study we tested varied phytochemicals belonging to diverse chemical classes such as phenols, carotenoids, flavonoids, terpenoids, indoles, tocopherol/trienols, etc. for their antiproliferative effects on two non small cell lung cancer (NSCLC) cell lines, H1299 (p53 null) and A549 (p53 WT). The terpenoid compounds were found to be the most potent. One such terpenoid, Cucurbitacin B, (CuB) used in folk medicine for centuries for its wide spectrum of pharmacological activities was used in this study to gain mechanistic insights into its anticancer effects on the NSCLC cells. CuB, exhibited a significant dose-dependant inhibitory effect on the growth of both cell lines with IC 50 in low nanomolar range as assayed by MTT and Cy-Quant cell proliferation assays. The cells underwent rapid morphologic changes after 10-30 mins of exposure to CuB as evidenced by phase-contrast microscopy, which might be suggestive of the impairment of actin filament organization and microtubule disruption. To understand the molecular basis of the putative anticancer activity, we investigated the effects of CuB treatment on cell cycle distribution and apoptosis. Flow cytometric analysis showed a significant dose dependent arrest of cells in the G2/M phase ofthe cell cycle in as early as 8 hrs. The down regulation of checkpoint protein Cyclin B was well correlated with the cell cycle arrest at G2/M. Apoptosis, assayed by ethidium bromide and acridine orange fluorescence staining revealed signs of nuclear condensation, nuclei fragmentation, and membrane blebbing with CuB treatment. Western blot analysis showed a dose dependent downregulation of anti-apoptotic protein Bcl2 and the proteolytic cleavage of PARP (Poly (ADP-ribose) polymerase) that is a known downstream target of Caspase-3 activation and one of the hall mark feature associated with apoptosis. Taken together our results suggest that CuB exhibits pleotropic effects on the cells inducing both cell cycle arrest and apoptosis and can have therapeutic effects on both p53- and p53+ non small cell lung cancer.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 3896.
THU0592 Pubertal delay despite intensive treatment of juvenile idiopathic arthritis: results of a longitudinal study
Authors: P. Van Pelt, A. Hokken-Koelega, R. Dolhain, A. Kruize, H. Bijlsma, N. Wulffraat
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Delayed puberty and reduced adult height have been reported in JIA before the era of biologicals. Long-term consequences of delayed puberty are among others growth disturbances, low bone mineral mass and decreased fertility. Treatment with anti-TNF restores growth, but data on puberty are unknown <h3>Objectives</h3> We evaluated onset and course of puberty and growth, in JIA-patients who are treated intensively, including the possibility of biologicals, and identified variables related with puberty and growth <h3>Methods</h3> In a longitudinal JIA-cohort, all consecutive patients (10–21 years) were followed for three years. Annual examinations were performed regarding demographic and disease-related items as well as Tanner pubertal stages and anthropometric measurements. Median ages at reaching each stage were estimated by Kaplan-Meier curves. Parametric tests were used to determine differences between patients and healthy controls, non-parametric tests between patient-groups. Univariate analyses and mixed models were used to identify associated variables <h3>Results</h3> 138 patients were included (66% girls). Median disease-duration was 7,8 years (IQR 3.7–10.5), median JADAS-27 3,7 (IQR 1,3–8,0), DAS-28 2,16.<sup>1,5–2,8</sup> Puberty onset was 1,2 years delayed in girls (p&lt;0,01), in boys 0,6 years (ns). The progression was also delayed: end-stage (Tanner-5) in girls was 3,3 years delayed (p&lt;0,01), in boys 1,7 years (p&lt;0,01). A positive association was found for longer disease-duration and a lower BMI. Biological-use was not associated. Both for girls and boys, standardised height was not different at the onset and at the end of puberty <h3>Conclusions</h3> In contrast to normalised longitudinal growth, we found in JIA-patients in disease remission or with low disease activity a delayed onset and progression of puberty despite intensive treatment including biologicals. Eventually, puberty was completed and normal adult height was reached. The effects on bone mass and fertility will have to be evaluated in cohort studies <h3>Acknowledgements</h3> <i>This study is financially supported by the Dutch Arthritis Association</i> Statistical support was provided by Reinier Timman and Kees A.G.M.van Montfort, department of biostatistics, Erasmus University Rotterdam. <h3>Disclosure of Interest</h3> None declared
AL Amyloidosis — Pathogenesis and Prognosis Are Determined By the Amyloidogenic Potential of the Light Chain and the Molecular Characteristics of Malignant Plasma Cells
Authors: Anja Seckinger, Ute Hegenbart, Susanne Beck, Martina Emde, Tilmann Bochtler, Christoph Kimmich, Carsten Müller-Tidow, Anna Jauch, Stefan Schönland, Dirk Hose
Journal: Blood (2018)
Safety and Efficacy of Liposomal Cytarabine/Daunorubicin (CPX-351) in Younger Patients &lt; 60 Years Old with Secondary Acute Myeloid Leukemia
Authors: Amanda Przespolewski, Chetasi Talati, Pankit Vachhani, Srinivasa Reddy Sanikommu, Swapna Thota, Jeffrey Baron, Elizabeth A. Griffiths, James E. Thompson, Kendra L. Sweet, Eunice S. Wang
Journal: Blood (2018)
AB0129 Assessment of morphology of the early and late stage of juvenile rheumatoid arthritis
Authors: M. Salokhiddinov, U. Anarmetova, G. Haydarova, I. Xodjanazarov
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> One of the current problems of modern rheumatology is chronic inflammatory diseases of the knee joint in children. With juvenile rheumatoid arthritis (JRA), an uncontrolled inflammatory process can lead to the formation of contractures and deformities of the limbs <h3>Objectives</h3> Our aim is to study morphology of the early and late stage of juvenile rheumatoid arthritis <h3>Methods</h3> In total, 81 knee joint surgery was performed on 71 children of the child age in connexion with the JRA. The average age of the patients was 11 years (6–14). To verify the diagnosis during diagnostic arthroscopy, a multifocal biopsy from 7 points was performed. Pathomorphological study of the material was performed according to the conventional histological method of studying soft tissues <h3>Results</h3> The results of the pathomorphological examination were analysed for the time frame of the appearance of the JRA. Pathomorphological early and late synovitis criteria were found. Early criteria (typical for the first three months after the JRA debut) – the phenomenon of necrosis in synoviocytes and the subintimal layer, palisade-like cell structures in the sub-synovial layer, synoviocyte proliferation, fibrinoid superimpositions on the surface of the cover layer, productive endovascular endo- lytic endotheliosis, lymphocyte infiltration and plasmocytes. Late criteria (duration of the disease – more than 3–6 months): marked plasmacytic infiltration with the formation of lymphoid nodules with a hermetic centre, activation of fibrinoid and sclerotic processes with the formation of extensive fibrinoid necrosis with perifocal sclerosis, the formation of rheumatoid nodules, productive synovial hyperplasia, deposition of amyloid masses, formation of pannus granulation tissue with destructively invasive growth articular cartilage and synovium <h3>Conclusions</h3> Determining the stage of JRA is of great clinical importance for the early initiation of treatment and prevention of irreversible destructive complications. The proposed new method for determining the prevalence of pathological changes in the synovial membrane of the knee joint in children with JRA using a combined arthroscopic and pathomorphological evaluation of pathological changes in synovium in 7 joints allows to accurately determine the prevalence of the pathological process in the synovium, which has macroscopically only local manifestations <h3>References</h3> [1] Gormley GJ, Steele WK, Gilliland A, et al. Can diagnostic triage by general practitioners or rheumatology nurses improve the positive predictive value of referrals to early arthritis clinics?Rheumatology2003;42(6):763–768. [2] Houssien DA, Scott DL. Early referral and outcome in rheumatoid arthritis. Scandinavian Journal of Rheumatology1998;27(4):300–302. <h3>Disclosure of Interest</h3> None declared
THU0151 Assessment of compliance of rheumatoid arthritis patients in cognitive dysfunction
Authors: E. Grunina, A. Tkachev
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Compliance decline may result in a decrease of treatment effectiveness in rheumatoid arthritis. RA patients had global cognitive impairment, which was associated with disease activity and immune changes.<sup>1</sup> Cognitive dysfunction may have a negative effect on the results of traditional methods of compliance assessment. <h3>Objectives</h3> Our aim was to develop the method of structured and algorithms interview to assess compliance and cognitive functions in patients with rheumatoid arthritis. <h3>Methods</h3> 240 patients fulfilling EULAR 2010 classification criteria for rheumatoid arthritis were examined. Pain in the joints was assessed using a visual analogue scale, the clock-drawing test was used, the structured and algorithms interview with clear determination of at least 3 levels of patient values was performed.<sup>2</sup> Each patient chose the subject of the interview: compliance, pain or side effects of drugs. Subjective values that determine the choice and behaviour of the patient with dichotomy, for example, taking or missing drugs were revealed. <h3>Results</h3> 162 patients chose the theme of the interview concerning of pain, 50 patients chose the theme compliance with drug therapy, 38 patients - side effects of drugs. The criteria of cognitive dysfunction were the following: inability for the patient to determine subjective values influencing the process of decision- making, repeating one value with inability to built a value hierarchy, a limited number of the levels of the value hierarchy. The indirect criterion was the duration of the structured interview as the measure of patient’s and interviewer’ s efforts. Cognitive dysfunction determined by the method of the structured interview was connected with the low score of the clock-drawing test. Compliance decline was noticed in the presence as well as in the absence of cognitive dysfunction. Determining values and their hierarchy may lead to the increase of patients’ compliance. <h3>Conclusions</h3> The method of the structured and algorithms interview with the assessment of the hierarchy of values is used to assess compliance and cognitive functions in patients with rheumatoid arthritis as well as to reveal the ways to increase compliance. <h3>References</h3> [1] Clin Rheumatol2018Jan 25. doi:10.1007/s10067-018-3990-9 [2] Luksha P, Tkachev A. Journal: Kybernetes, ISSN: 0368–492X, Year: 2007;36(7–8):956–971. doi:10.1108/03684920710777487 <h3>Disclosure of Interest</h3> None declared
SP0173 Stratifying primary sjogren’s syndrome patients
Authors: W.-F. Ng
Journal: Annals of the Rheumatic Diseases (2018)

<h3></h3> The clinical manifestations of primary Sjögren's syndrome (PSS) vary considerably between individual patients. The pathogenesis of PSS is not fully understood and although many aberrant biological pathways have been identified, the relationships between these pathways and clinical manifestations remain unclear. Furthermore, there is substantial heterogeneity in long-term outcomes and in health economic cost among patients with PSS. Stratification of PSS into more homogeneous subsets will facilitate better understanding of the pathogenesis of the disease, development of more cost-effective management strategies and accelerate therapeutic development programmes of targeted therapies in PSS. The establishment of several large cohorts of clinically well characterised PSS cohorts with associated biobanked materials has provided a rich resource for stratified medicine research in PSS. The growing number of datasets from clinical trials in PSS provide an excellent opportunity to evaluate the potential impact of stratified approach to therapy development in PSS. In this presentation, different approaches to identify clinically and biologically meaningful PSS subsets will be considered. In addition, the key challenges and potential future directions in Stratified Medicine in PSS will be discussed. <h3>Disclosure of Interest</h3> W.-F. Ng Grant/research support from: ElectroCore, Resolve Therapeutics, Nascient, Consultant for: GlaxoSmithKline, Novartis, Abbvie, MedImmune
AB0963 Calprotectin as a useful marker of inflammation in knee osteoarthritis
Authors: J. Calvet, C. Orellana, N. Navarro, C. Galisteo, J. Gratacós, M. Larrosa
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Low-grade synovial inflammation is known to be present in many patients with knee osteoarthritis and appears to have clinical and prognostic implications. Calprotectin seems to be more sensitive than CRP to detect minimal inflammatory activity in many inflammatory rheumatic diseases and could be a biomarker in osteoarhritis with inflammatory features. <h3>Objectives</h3> To determine the levels of synovial calprotectin in patients with knee osteoarthritis showing inflammatory traits and their relationship with clinical and ultrasonographic features and other proinflammatory markers. <h3>Methods</h3> Cross-sectional study with systematic inclusion of 108 symptomatic primary knee osteoarthritis patients (VAS&gt;4) with ultrasound-confirmed joint effusion. Age, physical exercise, knee osteoarthritis symptoms duration and different anthropometric measurements were collected. Radiographic severity was evaluated according to Kellgren-Lawrence scale. Pain and disability were assessed by WOMAC-pain and WOMAN-function. Calprotectin, TNF-alfa, IL-6 and high-sensitivity C-reactive protein (hs-CRP) were measured by ELISA in synovial fluid. Summary of clinical data and laboratory parameters and their association with WOMAC scales were performed using non-parametric methods. Medians and Spearman correlation (r) were used for continuous measures, and Mann-Whitney test was applied to categorical variables. This study was approved by the local ethics committee. <h3>Results</h3> Median higher synovial calprotectin levels were associated with worse WOMAC pain (671.5 vs 431.8 ng/mL, p&lt;0.05).) and function (713.4 vs 400.1 ng/mL, p&lt;0.05).) scores than patients with inferior levels. Patients with moderate to severe synovial effusion (&gt;8 mm on midline suprapatellar line) had higher calprotectin levels compared with those with mild effusion (626.1 vs 417.5 ng/mL, p&lt;0.05). Synovial calprotectin levels showed moderate correlations with intraarticular TNF-alfa levels (r=0.26), hs-CRP (r=0.27) and a high correlation with synovial IL-6 levels (r=0.53). <h3>Conclusions</h3> Calprotectin showed association with inflammatory features as measured by ultrasound and inflammatory markers such as hs-CRP, TNF-alfa and IL-6, and was related to pain and function in patients with knee osteoarthritis with inflammatory features. Calprotectin appears to be a useful marker of inflammation and could be a useful marker for assessing response to treatments targeting inflammation. <h3>Disclosure of Interest</h3> None declared
THU0368 Are anti-phosphatidylserine prothrombin antibodies a useful screening tool for the lupus anticoagulant?
Authors: M.M. Pham, G. Orsolini, C.S. Crowson, M.R. Snyder, R.K. Pruthi, K.G. Moder
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Anti-phosphatidylserine prothrombin antibodies (PSPT) have been reported to be strongly associated with the lupus anticoagulant (LAC) in established antiphospholipid syndrome (APS) and autoimmune cohorts. However, there is a paucity of similar studies assessing clinical utility on an all-comer patient population undergoing evaluation for suspicions of APS. <h3>Objectives</h3> To determine the sensitivity and specificity of IgG and IgM PSPT to the LAC in patients undergoing evaluation for APS. <h3>Methods</h3> Patients from June 2017 to December 2017 undergoing evaluation for APS had blood draws for the LAC, anti-cardiolipin (aCL), anti-β2 glycoprotein-1 (β2GP1), and PSPT. Both IgG and IgM isotypes were tested for each antibody. Presence of the LAC was determined by trained haematologists interpreting a number of mixing and neutralisation studies. Demographic details were abstracted from the medical record and cases meeting the SLICC criteria for systemic lupus erythematosus (SLE) and the revised Sapporo criteria for APS were enumerated. <h3>Results</h3> Fifty six eligible patients were identified. Mean age was 50±18 years. 68% were female, 20% with SLE, and 20% with APS. At time of testing, 18% were on warfarin, 7% on direct factor Xa inhibitors and 2% on low-molecular weight heparin. The LAC was negative in 45% (25/56) of those tested. In LAC negative cases, the IgG and IgM PSPT were negative in 100% and 92% of cases, respectively. In LAC positive cases, IgG PSPT was positive in 35% and IgM PSPT was positive in 61%. Compared to the LAC, IgG PSPT was 100% (95% CI: 72%, 100%) sensitive but was only 56% (40%, 70%) specific. Similarly, the IgM isotype of PSPT showed 90% (70%, 99%) sensitivity but only 66% (48%, 81%) specificity. Overall, 38% (21/56) of the cases possessed an isolated, singly positive LAC with concurrent negative IgG/M aCL and β2GP1 antibodies. In this isolated LAC positive-only group, further testing with IgG and IgM PSPT was positive in 38% and 57% of the cases, respectively. <h3>Conclusions</h3> In this study, IgG and IgM PSPT were found to be highly sensitive to the LAC and may be a useful tool in the screening of and the interpretation of the LAC. <h3>References</h3> [1] Akhter E, Shums Z, Norman GL, Binder W, Fang H, Petri M. The Journal of Rheumatology2013;40(3):282–6. [2] Atsumi T, Ieko M, Bertolaccini ML, et al. Arthritis &amp; Rheumatism2000;43:1982–93. [3] Bertolaccini ML, Sciascia S, Murru V, Garcia-Fernandez C, Sanna G, Khamashta MA. Thrombosis and Haemostasis2013;110:207–13. [4] Pregnolato F, Chighizola CB, Encabo S, et al. Immunologic Research2013;56:432–8. [5] Vlagea A, Gil A, Cuesta MV, et al. Clinical and Applied Thrombosis/Hemostasis2013;19:289–96. <h3>Acknowledgements</h3> Special thanks to Susan Hartzler, Cory Blixt, Serena Navitskas, and Diane Meier. <h3>Disclosure of Interest</h3> None declared
Overexpression of CD49d in trisomy 12 chronic lymphocytic leukemia patients is mediated by IRF4 through induction of IKAROS
Authors: Stefania Fiorcari, Stefania Benatti, Antonella Zucchetto, Patrizia Zucchini, Valter Gattei, Mario Luppi, Roberto Marasca, Rossana Maffei
Journal: Leukemia (2019)
Abstract 20966: Increasing Cav1.2 in Smooth Muscle Cells Has Different Effects on Vascular Remodeling Dependent of Insults
Authors: Ying Zhang, Jian Zhou, Xioaying Zhang, Chen Zhang, Ying H Shen, Xiongwen Chen
Journal: Circulation (2017)

Introduction: Increasing Calcium (Ca 2+ ) influx through the L-type Ca 2+ channel (Cav1.2) increases smooth muscle cell (SMC) contractility while the loss of Cav1.2 is associated with enhanced SMC remodeling. However, increasing Ca 2+ influx into SMCs through non-Cav1.2 routes is often associated with enhanced vascular remodeling under pathological conditions. Whether increasing Cav1.2 in SMCs may inhibit or promote SMC remodeling is unclear. Hypothesis: Increasing Cav1.2 in SMC protects SMCs from remodeling. Methods: Transgenic mice with SMC-specific overexpression of Cavβ2a and control mice were subjected to carotid artery ligation or aneurysm induction (high fat feeding for 2 months and then HFD+AngII infusion for 1 month) to study vascular remodeling. Results: 1. The Cav1.2 current in SMCs from middle cerebral artery was increased by 98.5±5.4%; 2. The left common carotid artery (LCCA) close to the internal and external arterial bifurcation were completely ligated. After ligation for 3 weeks, there were less thickening of the media and less neointima formation in LCCA region proximal to the ligation in TG (n=8) than in control (n=8) mice; in accordance, there were less EdU labelled cells in TG. The surface area of TG SMCs was not increased as such as in the control. 3. HFD+AngII induces higher frequency (10/10 in TG vs. 4/13 in control) of aneurysm/aortic dilation segments. Among the mice with aortic aneurysm/dilation, the average number of segments of aneurysm/arotic dilation in each mouse was higher in TG (2.7±0.2) than in control (1.3±0.2) mice. The TG mice had thinner vascular wall, larger aneurysmal area accompanied with more severe elastin and middle layer degradation, and more inflammatory cell infiltration in the aortic aneurysm/dilation region than control mice. 4. Rat smooth muscle cells in culture infected with Cavβ2a-GFP adenoviruses (MOI=10) had less proliferation (both total number of cells and EdU + cells) but more death (LDH and TUNEL+) than rat SMCs infected with AdGFP (MOI=10). Less collagen synthesis was observed in rat SMCs infected with Ad Cavβ2a-GFP. Conclusions: Increased Cav1.2 in SMCs may inhibit or promote vascular smooth muscle remodeling depending on the injury nature.