tbuckley/cabot-search huggingface dataset:
Abstract 2768: Molecular properties and antiproliferative activity against tumor cells of a new poly-alkylamino-bis-maltolic synthetic molecule (maltonis).
Authors: Maria Cristina Manara, Mirco Fanelli, Stefano Amatori, Clara Guerzoni, Lorena Landuzzi, Pier-Luigi Lollini, Luca Giorgi, Vieri Fusi, Katia Scotlandi
Journal: Cancer Research (2013)

Abstract Introduction Hydroxypyrones are highly versatile molecules and several members of this family, both alone and in combination with metals, were found to exert anti-proliferative activities against a wide range of tumor cells. In this study, we show the anti-tumor potential of the prototype of new molecules belonging to the family of hydroxypyrones, named maltonis [4(N),10(N)-bis[(3- hydroxy-4-pyron-2-yl)methyl]-1,7-dimethyl-1,4,7,10-tetraazacyclododecane], in different tumor cell lines (derived from both hematopoietic and solid human tumors). Methods and Results We examined the potential of maltonis to induce, in cell-free assays, covalent modifications of DNA structure, together with anticancer activities (cell growth inhibition, cell cycle perturbations, effects on programmed cell death). The cellular response to maltonis treatment was assessed also at the molecular level by evaluation of the transcript level of genes involved in cell cycle and programmed cell death regulation. The possible induction of a maltonis-mediated DNA damage response was investigated monitoring the histone H2AX phosphorylation (γH2AX). Sarcoma cell lines appeared to be particularly sensitive to maltonis in in vitro assays. Consistently, preliminary in vivo experiments reported a cytostatic effect of maltonis, monitoring a consistent reduction of the neoplastic lesions, when intra-tumor injected at doses of 20/40 mg/kg (for two weeks) in a xenograft model of Ewing Sarcoma. However, a range of different levels of sensitivity was observed in the different histotypes (osteosarcoma, Ewing sarcoma and rhabdomyosarcoma) and among cell lines, indicating the need of further studies to identify markers of efficacy. Conclusions Taken together, these results show that maltonis appears to be a good candidate for sarcoma treatment. It induces complex DNA structural modifications, which need to be further analysed in order to clarify mechanisms of action and efficacy of this new drug. Grants from: AIRC 10452 and Ministry of Health_RF2008 to KS; A.S.S.O., PRIN 2008 and PRIN 2009 to MF and VF. Citation Format: Maria Cristina Manara, Mirco Fanelli, Stefano Amatori, Clara Guerzoni, Lorena Landuzzi, Pier-Luigi Lollini, Luca Giorgi, Vieri Fusi, Katia Scotlandi. Molecular properties and antiproliferative activity against tumor cells of a new poly-alkylamino-bis-maltolic synthetic molecule (maltonis). [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 2768. doi:10.1158/1538-7445.AM2013-2768
Steroids and Addisonian Pernicious Anemia
Authors: S. Ardeman, I. Chanarin
Journal: New England Journal of Medicine (1965)

ADMINISTRATION of steroids to patients with Addisonian pernicious anemia in relapse often produces a hematologic response.1 There is an improvement in vitamin B12 absorption2 3 4 and with it an increase in secretion of intrinsic factor5 and a decline in the amount of intrinsic-factor antibody in the blood.6 The absorption of vitamin B12 after total gastrectomy is not improved by steroid therapy.7 There is good evidence that gastric atrophy is the result of an autoimmune process. It is also possible that the final failure of vitamin B12 absorption in pernicious anemia follows the development of antibodies against intrinsic factor. . . .
SP0078 Cognitive Mechanisms of Change in Multidisciplinary Treatment of Patients with Chronic Widespread Pain
Authors: A. De Rooij
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Multidisciplinary treatment programs are recommended in patients with CWP and its associated problems. Multidisciplinary treatment in CWP addresses a variety of cognitive mechanisms. However, the cognitive mechanisms of change in the multidisciplinary treatment of patients with chronic widespread pain (CWP) are only partially understood. <h3>Objective</h3> To evaluate the contribution of improvement in negative emotional cognitions, active cognitive coping, and control and chronicity beliefs to the outcome of the multidisciplinary treatment in patients with chronic widespread pain (CWP). <h3>Methods</h3> Data were used from baseline, 6 months and 18 months follow-up of a prospective cohort study of 120 CWP patients who completed a multidisciplinary pain management treatment. Longitudinal relationships were analyzed between changes in cognitions and outcome, using generalized estimated equations. Outcome domains included: pain, interference of pain in daily life, depression, and global perceived effect. Cognitive domains included 1) negative emotional cognitions; negative and emotional thoughts that hinder adjustment to chronic pain, 2) active cognitive coping; cognitive efforts of a person to manage or undo the negative influence of pain, and 3) control and chronicity beliefs; thoughts and expectations about the controllability and chronicity of the illness. <h3>Results</h3> Improvements in negative emotional cognitions were associated with improvements in all outcome domains, in particular with improvement in interference of pain with daily life and depression (between baseline and 6 months and 6 and 18 months). Improvements in active cognitive coping were associated with improvements in interference of pain in daily life (between baseline and 6 months). Finally, improvements in control and chronicity beliefs were associated with improvements in pain and depression (between 6 and 18 months). <h3>Conclusions</h3> Improvement in negative emotional cognitions seems to be a key mechanism of change of multidisciplinary treatment in CWP. Improvement of active cognitive coping and improvement of control and chronic timeline beliefs may constitute mechanisms of change as well, although the evidence is less strong. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6214
296Connexin43 expression modulate myofibroblasts mechanical coupling: implication for the infarct borderzone expansion
Authors: M Miragoli, F Schultz, A Vite, DA Pijnappels, MJ Lab, J Gorelik
Journal: Cardiovascular Research (2014)

Infarct borderzone (BZ) expansion following myocardial infarction is accompanied by ventricular dilatation, remodeling, and heart failure. We showed that myofibroblasts (MFBs), which are present in the BZ, tend to form functional gap junctions with adjacent cardiomyocytes (CMs) in-vitro and such heterocellular pairing depolarizes CMs, induces discontinuity in conduction, and slows impulse propagation. Connexin-43 (C×43) plays an important role in establishing the electrical coupling, but its involvement in the dynamics of heterocellular pairing has never been investigated in live cells, due to the limit of the nanoscale resolution. We cultured neonatal rat CMs and MFBs as a culture model of BZ and followed the dynamics of contacts formed between these two cell types. We first seeded the CMs (0.5×103 cell /mm2) and, after 24 hrs, we seeded either wild type or C×43-deficient MFBs (0.15×103 cell/mm2). After another 24 hrs, preparations were mounted in a temperature controlled chamber and perfused with HBSS containing 1% serum. The mobility of the BZ was examined at 36°C using Scanning Ion Conductance Microscopy. We collected consecutive images of live-coupled areas (∼15 μm2) at 4 min. per scan over 60-70 min. The images were analysed in randomly selected points on the BZ to extract information on the movement of cell-cell contact points using a Matlab-based software.
FUSION OF INTRAVASCULAR ULTRASOUND AND OPTICAL COHERENCE TOMOGRAPHY IMAGINGS TO COMPREHENSIVELY ASSESS CALCIFIED PLAQUE DEVELOPMENT IN- AND OUT-SCAFFOLD SEGMENTS AFTER BIORESORBABLE ABSORB SCAFFOLD IMPLANTATION
Authors: Yaping Zeng, Hiroki Tateishi, Erhan Tenekecioglu, Rafael Cavalcante, Pannipa Suwannsom, Yohei Sotomi, Felipe Albuquerque, Yoshinobu Onuma, Patrick Serruys
Journal: Journal of the American College of Cardiology (2016)
THU0386 Seven Cases of Multicentric Reticulohistiocytosis Treated with Intravenous Administration of Alendronate
Authors: K. Hamamoto, H. Goto, S. Yamada, M. Yoda, K. Yoda, Y. Imanishi, M. Inaba
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Multicentric reticulohistiocytosis (MR) is a rare systemic disorder characterized by cutaneous papulonodular lesions and severe destructive arthritis. Histologic analysis of cutaneous and synovial lesions discloses infiltration by multinucleated foreign body-type giant cells and smaller histiocytes. There is no consistently effective therapy for MR. It was reported that aminobisphosphonates such as alendronate act directly on macrophages by inhibiting the mevalonate pathway and that bisphosphonates have anti-inflammatory and anti-arthritic effects in animal models of arthritis. For these reason we tried to treat MR with aminobisphosphonates and reported the first case of successful treatment of MR with intravenous administration of alendronate in 2003. <h3>Objectives</h3> To verify efficacy of alendronate for MR, seven MR patients (1 male and 7 females, mean age of 55.1 (30-75) years) were treated with alendronate intravenously. <h3>Methods</h3> Alendronate was given intravenously 10 mg once a month for one year to each patient. Other drugs previously started were continued. <h3>Results</h3> Skin manifestation and arthritis were markedly improved in all seven cases. Three cases stayed in remission status after treatment completed. Two cases stayed in remission however continuation of maintenance administration of alendronate was necessary. One severe case showed improvement of existing skin lesion and arthritis, but developed new skin and mucomembranous lesion. One male case showed flare-up one year after completion of treatment but improved again after resection of newly diagnosed epididymis tumor. Except for transient fever in two cases, alendronate has not caused any other adverse event including bisphosphonate-related osteonecrosis of the jaw. In all cases joint pain and activity of daily living was markedly improved, however bone erosions were not improved. <h3>Conclusions</h3> Alendronate may be the first line drug for MR treatment that may produce a remission, and may be safer than conventional treatment such as immunosuppressant, more over can be used with any other treatment. <h3>References</h3> Arthr Rheum 2003 48: 3538-41. <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5879
AB0974 Reproducibility of Magnetic Resonance Diffusion Weighted Imaging in Axial Spondyloarthritis Patients and Healthy Subjects: Table 1.
Authors: J.M. Møller, I.J. Sørensen, H.S. Thomsen, M. Østerggard, O.R. Madsen, S.J. Pedersen
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Diffusion weighted imaging (DWI) is a magnetic resonance imaging (MRI) technique where the image contrast is dependent on the diffusion of the extracellular free water molecules. DWI is widely used in oncology imaging, but only few papers address DWI in spondyloarthritis (SpA). From DWI the apparent diffusion coefficient (ADC) can be calculated and hence the diffusion in a region of interest (ROI) can be quantified. The water diffusion reflects the cellularity and thus it may be used as a quantification of inflammatory cells. <h3>Objectives</h3> The aim of the study was to measure the reproducibility of DWI in SpA patients and healthy subjects. <h3>Methods</h3> 25 SpA patients (13 females, mean age 36.1 years (SD 9.6); 12 males, mean age 42.3 (SD10.8) and 24 healthy subjects (13 females, mean age 42.7 (SD 13.2); 11 males, mean age 45.3 (SD 7.5)) were MRI examined at 1.5T two times with a mean interval of 6.8 days (SD 0.9). A 5mm (gap 1.2mm) sagittal single-shot echo-planar imaging DW sequence with four b values (0;50;500;800) and a resolution of 2mm x 1.65mm was performed on Th6 to L5. ADC maps were calculated based on all b values. The MRIs were anonymized and read in random order without information on time point and clinical data. On ADC maps 50mm<sup>2</sup> circular ROIs were placed in each vertebral corner just inside cortex. ADC was measured on the sagittal slice in the middle of the spine and on the adjacent slice to the right and left to the middle. ADCs from the four ROIs were pooled. Another ROI was placed in the right and left pedicle and in the spinous process from L1 to L5. The inter-reader variability was measured by intra-class correlation coefficient (ICC). Intra-reader variability was measured by a second reading of the examinations at time point (TP) 2. <h3>Results</h3> Overall ICC of the vertebral bodies between TP1 and TP2 was 0.80 (95% CI: 0,77-0.83). At TP1, ICC between the right and middle slice was 0.89 (95% CI: 0.87-0.90) and between left and middle slice 0.89 (95% CI: 0.87-0.90). Intra-reader reliability was 0.94 (95% CI: 0.93-0.95). For the right pedicle ICC was 0.44 (95% CI: 0.33-0.54), for the left pedicle 0.49 (95% CI: 0.39-0.58), for the spinous processes 0.20 (95% CI: 0.07-0.32) <h3>Conclusions</h3> MR DWI is overall a reproducible imaging sequence performed in the sagittal plane. The reproducibility is better in the lumbar spine compared to lower thoracic spine. Pedicles and spinous proceses are not reliably imaged by DWI. <h3>References</h3> Gaspersic et al. Skeletal Radiol. 2008;37:123-31. Koh et al. AJR Am J Roentgenol. 2007;188:1622-35. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2009
Novel Biospecific Agents for the Treatment of Myelodysplastic Syndromes
Authors: Jason Gotlib, Peter L. Greenberg
Journal: Journal of the National Comprehensive Cancer Network (2003)

Levels of treatment for patients with myelodysplastic syndromes (MDS) fall within 3 broad categories: supportive care, low- and high-intensity therapy. Most approaches remain experimental, and supportive care remains the standard of treatment in MDS. In parallel with the growing knowledge of the multiple pathobiologic abnormalities in MDS, increasing numbers of low-intensity, biospecific agents that target these pathogenetic lesions have entered clinical trial testing. Although the term “biospecific” has been applied to many of these investigational drugs, they often exert pleiotropic effects, many of which remain to be identified. An ongoing challenge will be to more fully characterize the mechanisms of action of these drugs and to characterize biologic correlates of response. With these data in hand, it will be increasingly feasible to treat patients with combinations of biospecific drugs with non-overlapping actions and toxicities, a therapeutic approach that is likely required to effectively overcome the barriers posed by the biologic heterogeneity of MDS. This review focuses on recent therapeutic approaches using such biologic response modifiers to treat MDS.
Endoscopic minimal invasive methods for drainage of pancreatic cysts and abscesses: 3-year results from a single centre
Authors: O Al-Mukhtar, B Erlandsson, M Bergström, PO Park
Journal: Endoscopy (2012)

Objective of the study: As an alternative to open surgery laparoscopic, endoscopic and interventional radiology has been developed to treat complications of acute pancreatitis. These methods carry less morbidity and mortality than open surgical treatment.
P244 Adherence with department of health guidelines for the management of pandemic H1N1 influenza in secondary care
Authors: M. M. Khan, R. B. Gore, S. J. Fowler
Journal: Thorax (2010)

<h3>Background</h3> Prior to the 2009 swine flu pandemic, there was uncertainty about the expected incidence, morbidity and mortality from the disease. The Department of Health (DoH) compiled guidelines for assessment and management of children and adults admitted to hospital with suspected H1N1 infection. <h3>Objectives</h3> We evaluated whether adults with suspected H1N1 infection were appropriately diagnosed, investigated and managed within an NHS Foundation Trust during a period of maximal incidence when DoH guidance was accessible, with the aim of improving care for patients during future pandemic flu outbreaks and utilising hospital resources efficiently. <h3>Methods</h3> Patient notes of suspected cases of adult H1N1 infection between July and December 2009 were retrospectively reviewed to identify how many met the diagnostic criteria, underwent relevant investigations and were prescribed a neuraminidase inhibitor as compared with DoH guidelines. The relationship between the initial consultant9s diagnosis and the final diagnosis was also considered. <h3>Results</h3> Seventy cases of suspected swine flu were identified, and full documentation was available for review in 61 of these. All patients were tested for swine flu and overall 26% of patients were H1N1 positive, including 6% of those patients who did not fulfil the diagnostic criteria. Of patients clinically suspected of having swine flu 34 (56%) did not fulfil the diagnostic criteria, although two of those. were found to be H1N1 positive. Minimum recommended investigations were performed as follows; routine bloods and chest x-ray in 85%; blood cultures in 33%; sputum cultures in 15%; and urinary pneumococcal antigen testing in 3%. Antiviral medication was not prescribed in 31%of patients suspected of having swine flu. In 74% of the cases, the initial consultant9s diagnosis matched the final diagnosis; this was true for 70% of the patients who were H1N1 positive. <h3>Conclusions</h3> Increased awareness of the available guidelines is required to optimise diagnosis and management, and minimise the likelihood of potentially unsafe, incorrect diagnoses. This requires education of healthcare staff of available guidance, and further audit following the next outbreak of pandemic flu with the aim of safely and efficiently guiding clinical practice.
Abstract 2712: Identification of tumor initiating genes RPL39 and MLF2 that mediate lung metastasis through nitric oxide signaling and mesenchymal to epithelial transition.
Authors: Bhuvanesh Dave, Sergio Granados, Junhua Mai, Dong Soon Choi, Ding Cheng Gao, Sucharita Mitra, Haifa Shen, Senthil Muthuswamy, Vivek Mittal, Mauro Ferrari, Jenny Chang
Journal: Cancer Research (2013)

Abstract Triple negative breast cancer (TNBC) is the most aggressive and lethal form of cancer characterized by lack of estrogen, progesterone and Her2 receptors. It is prevalent in women of African American descent, often present in younger and premenopausal women. It shows high risk of recurrence and frequently metastasizes to lungs and brain, resulting in poor overall prognosis. There is no targeted therapy for TNBC as it does not respond to hormonal therapy and is intrinsically resistance to conventional chemotherapy. It is therefore imperative to understand the mechanism of survival of these cancers and unravel its biological pathways and modes of progression. We have previously described breast cancer stem cells (BCSC) to be intrinsically resistant to treatment which is further confirmed by recent publications by other groups that describe direct functional evidence for the same. Using genomic assays, we traced a BCSC gene signature comprising of 477 genes derived from patient biopsies. On selective shRNA knockdown of these genes we identified RPL39 and MLF2 as the top two candidates that affect BCSC self-renewal. Selective siRNA knockdown of RPL39 and MLF2 in human cancer xenografts, showed reduced tumor volume and lung metastases with a concomitant decrease in BCSC markers. Thus, targeting BCSCs in combination with chemotherapy should eliminate the heterogeneous populations within a tumor. Additionally, next generation RNA-seq confirmed mutations in RPL39 and MLF2 in 50% of lung metastases from breast cancer patients. In vitro and in vivo siRNA knockdown of RPL39 and MLF2 showed decrease in nitric oxide synthase, suggesting that these genes are driven by nitric oxide signaling. In conclusion this study reveals novel tumor initiating genes, RPL39 and MLF2 that target the breast cancer stem cells and also show impact on lung metastasis. Our findings enhance the understanding of treatment resistant breast cancer stem cells, the mutations that cause metastases and also lay foundation for developing new therapies for such cancers with poor prognosis. Citation Format: Bhuvanesh Dave, Sergio Granados, Junhua Mai, Dong Soon Choi, Ding Cheng Gao, Sucharita Mitra, Haifa Shen, Senthil Muthuswamy, Vivek Mittal, Mauro Ferrari, Jenny Chang. Identification of tumor initiating genes RPL39 and MLF2 that mediate lung metastasis through nitric oxide signaling and mesenchymal to epithelial transition. [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 2712. doi:10.1158/1538-7445.AM2013-2712
SP0099 Myopathy in systemic sclerosis
Authors: B. Maurer
Journal: Annals of the Rheumatic Diseases (2013)

Patients with systemic sclerosis (SSc) frequently report muscle weakness. The prevalence of muscle involvement in SSc, however, varies largely, and numbers range from 5-96%. Muscle weakness due to direct involvement of skeletal muscles in the disease process needs to be distinguished from myopathy secondary to disuse (fatigue, articular disease, cardiopulmonary involvement), cachectic atrophy, or from medications (statins, antimalarials etc.). Laboratory features such as elevation of muscle enzymes in patients' serum may additionally contribute to the varying prevalence since in some patients, muscle enzymes may be only moderately elevated or be completely within normal limits despite the simultaneous myopathy as proven by a myopathic electromyogram (EMG) or a skeletal muscle biopsy. Furthermore, there is no consensus whether or not an inflammatory myopathy in SSc should be merely considered as an organ complication of SSc or as SSc-myositis overlap. To illustrate possible pitfalls in diagnosing SSc-associated myopathy and scleroderma-polymyositis overlap, we will present two different cases by highlighting the clinical symptoms and diagnostic procedures and discuss current treatment options. Based on the two case studies, we will demonstrate that the aetiology of SSc-associated myopathy is heterogenous and that there is an unmet need for the development of diagnostic consensus criteria, treatment recommendations and outcome measures. <h3>Disclosure of Interest</h3> None Declared