tbuckley/cabot-search huggingface dataset:
Effects of switching aromatase inhibitors on arthralgia: the ATOLL study.
Authors: K Briot, L Bastit, M Rotarsky, D Spaeth, M Tubiana, I Mauresan Kloos, I Bourdeix, C Roux
Journal: Cancer Research (2009)

Abstract Abstract #1142 Background: Aromatase inhibitors (AIs) are standard adjuvant therapy in postmenopausal women (PMW) with hormone receptor-positive breast cancer (HR+BC). The estrogen-deficient environment induced by AIs may predispose women to increased bone loss and arthralgia. Switching from one AI to another has been shown to improve arthralgia. However, clinical trial data documenting the course of joint pain symptoms in switching studies has been sparse. The Articular Tolerance of Letrozole (ATOLL) study evaluates the tolerability of letrozole (L) in patients who were switched from anastrozole (A) due to severe joint pain.&amp;#x2028; Objectives: This study included PMW with HR+BC who experienced severe joint pain with A requiring discontinuation and then switched to L. The aim of the study was to (i) determine the incidence of L discontinuation due to joint pain (ii) identify predictive factors for L tolerance.&amp;#x2028; Methods: Only PMW with HR+ BCwho experienced severe joint pain on A requiring discontinuation were eligible for this 6-month prospective open-label, multi-centre trial. Treatment with L was initiated following a 1 month washout period. Pain assessment was done by a oncologist just prior to L initiation and after six months of follow up. Outcomes were based on patient reports of joint pain after initiating L. A central review was done by a rheumatologist. Statistical evaluations were determined on a 95% CI, and correlations were performed using a Cox model.&amp;#x2028; Results: 179 PMW with HR+ breast cancer (mean age 61.3 ± 8.4) were eligible. The mean duration of A treatment prior to discontinuation was 14.6 ± 10.59 months with 126 (73.7%) on A for more than 6 months. At the end of the 6 month follow-up, 128 patients (71.5%) remained on L and continued by choice while 51(28.5%) patients discontinued L due to worsening of joint pain;73.5% patients discontinued due to arthralgia and 21% due to muscle pain . Hands, knees and spine were the most commonly affected joints. There was no association between L discontinuation with age, duration of menopause, socio-demographic status or previous joint disorders including osteoarthritis. The predictor of L discontinuation was significant only for the duration of the previous A treatment (p=0.04).&amp;#x2028; Conclusion: These data suggest switching from anastrozole to letrozole may help to maintain the benefit of AI therapy in patients who complain with severe joint pain and support the reported findings of Renshaw et al that more than 50% of women obtained relief of joint pain by switching from one AI to another. Symptomatic arthralgia due to prolonged use of A reduced the usefulness of switching to L in this patient cohort, therefore, switching from one AI to the other at the onset of symptoms may help to maintain the benefit of AI therapy in patients who complain of severe joint pain. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1142.
Abstract 4726: Phagocytic regulation through exogenous caffeine exposure in whole-blood macrophages.
Authors: Ryan Steck, Marcus Gustafsson, PingGuo Liu, Atif Elnaggar, Richard A. Robison, Kim L. O'Neill
Journal: Cancer Research (2013)

Abstract Caffeine is the most widely used neurostimulant in the world, and it has been shown that 79% of the United States population drinks coffee at least occasionally. Previous research has suggested that caffeine may be involved in the regulation of phagocytosis in immune cells through anti-inflammatory and pro-inflammatory signals. To investigate this effect, we used a macrophage engulfment assay, which was optimized in our lab to measure phagocytosis after exogenous caffeine exposure. Human leukocytes were isolated and incubated to allow for monocyte differentiation. After being allowed to differentiate for 1hr, 24hrs, 3-days, or 7-days, macrophages were incubated with varying concentrations of caffeine (35 μM-20 mM) for 1-24 hours. Cells were treated with lipopolysaccharide, and then incubated for 2 hours with fluorescently-labeled microspheres conditioned by incubation with fetal bovine serum. Engulfment was measured using flow cytometry, indicating the phagocytosis of microspheres in integral ratios. It was observed that engulfment was dependent on cell differentiation time, as well as caffeine concentration and exposure time. After &amp;lt;12 hour differentiation, cells exposed to caffeine showed a concentration-dependent reduction in engulfment when compared to those that were not treated. During incubation for 12 - 72 hours, however, results showed a 20% down-regulation of engulfment at &amp;lt;5 mM caffeine, whereas those cells exposed to 5-10 mM caffeine exhibited a 20% higher-engulfing phenotype, compared to the controls. At caffeine concentrations above 10 mM cell viability and engulfment was decreased up to 50%. It was concluded that the effect of caffeine on macrophages is dependent on incubation time and concentration, as well as the state of macrophage differentiation. Because of the implications of macrophage phenotype in many diseases involving inflammation, including cancer, these findings suggest further research should be continued to explore the therapeutic potential of caffeine and/or its analogs. Citation Format: Ryan Steck, Marcus Gustafsson, PingGuo Liu, Atif Elnaggar, Richard A. Robison, Kim L. O'Neill. Phagocytic regulation through exogenous caffeine exposure in whole-blood macrophages. [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 4726. doi:10.1158/1538-7445.AM2013-4726
SAT0286 Serum Immunoglobulin Free Light Chain Assessment in Psoriatic Arthritis
Authors: G. Assmann, S. Zinke, J. T. Ney, M. F. Ong, F. Neumann, S. Nold, M. Pfreundschuh
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Elevation of free light chains (FLC) represents B cell activation and has been detected in the autoantibodies positive rheumatologic disorders such as rheumatoid arthritis (RA) and Sjögren syndrome. Psoriatic arthritis (PsA) is typically not accompanied by autoantibodies, however, B cells have been found in PsA synovium (Ref1). <h3>Objectives</h3> We have conducted a case control study to evaluate the frequency of elevated serum FLC free kappa and free lamda levels in 210 PsA patients to detect polyclonal or monoclonal aberration. <h3>Methods</h3> Serum FLC levels were measured using the Freelite immunoassay (The Binding Site, Germany) to detect free kappa (normal range 3.3-19.4 mg/l) and lamda (5.7-26.3). Increased free kappa and free lamda levels were defined as polyclonal, a kappa/lamda ratio &lt;0.26 or &gt;1.65 was defined as monoclonal aberration. As controls served healthy controls (n=50), RA patients (n=75) and B-NHLymphoma (n=288). A subgroup analysis was performed after stratification of PsA patients into age, disease duration, development of joint erosions, biological treatment, elevated TNF alpha serum levels. <h3>Results</h3> PsA patients showed significantly less frequently polyclonal respectively monoclonal increase of FLC (7.1 and 3.8%) compared to RA (10.7 and 10.7%, **p=0.001) and B-NHLymphoma (11.5 and 10.1%, ***p=0.001), but more than in healthy controls (*p=0.001, figure 1). PsA patients with increased TNF alpha serum levels and patients with erosive joint disease had significantly more frequently polyclonal aberrations. <h3>Image/graph</h3> <h3>Conclusions</h3> Subgroups of PsA patients showed polyclonal aberrations measured by serum FLC indicating B cell activation in the course of disease. <h3>References</h3> Cantete JD, et al. Ectopic lymphoid neogenesis in psoriatic arthritis. ARD 2007;66,720-26 <h3>Disclosure of Interest</h3> G. Assmann Grant/research support from: THE BINDING SITE, Schwetzingen, Germany, put the FREELITE immunoassay at costfree disposal for G Assmann, S. Zinke: None Declared, J. T. Ney: None Declared, M. F. Ong: None Declared, F. Neumann: None Declared, S. Nold: None Declared, M. Pfreundschuh: None Declared
Role of Reduced Suppression of Glucose Production and Diminished Early Insulin Release in Impaired Glucose Tolerance
Authors: Asimina Mitrakou, David Kelley, Marian Mokan, Thiemo Veneman, Thomas Pangburn, James Reilly, John Gerich
Journal: New England Journal of Medicine (1992)

Insulin resistance and impaired insulin secretion both occur in non-insulin-dependent diabetes (NIDDM), but their relative importance is unclear. Hyperglycemia itself has adverse effects on tissue insulin sensitivity and insulin secretion that make it difficult to distinguish between primary and secondary abnormalities. To avoid this problem we studied subjects with postprandial glucose intolerance but not sustained hyperglycemia.
Abstract 5017: Comprehensive analyses of the T cell-mediated adaptive immune function in the elderly melanoma patients
Authors: Upendra P. Hegde, Meeta Yadav, Nitya G. Chakraborty
Journal: Cancer Research (2011)

Abstract Introduction: The incidence of melanoma is rising at a rapid rate in elderly population. Melanoma is an immunogenic tumor but T lymphocyte in the elderly persons are believed to be hypo/dysfunctional. Methods: HLA-A2 positive eleven elderly and eight young patients (median age 82 Y and 48 Y respectively) participated in the IRB approved study following informed consent. Peripheral blood (PB) derived CD8+ cytotoxic T lymphocytes (CTL), CD4+ helper T lymphocytes (TL) and CD4+CD25+ natural regulatory (nTreg) were used. Mart-1 and flu peptide was presented through PB derived antigen presenting cells (APC) to respective autologous CD8+ T cells to generate antigen specific CTL. The respective CD8+ and CD4+ cells from six elderly and 5 young patients, were engineered to express MHC class I restricted Mart-1 specific TCR and tested in functional assays. nT reg cells were tested for suppressive effect upon anti-CD3 mediated proliferation of autologous CD4+CD25- cells. Results: We found no significant differences in transduction efficiencies of Mart-1 specific TCR between young and old patients. Both Mart-1 and Flu specific CTL could be generated from all the 11 elderly and eight young patients. In vitro expanded antigen specific T effector cell responses were also comparable with inherent and engineered TCR between the two age groups. The elderly group, however, exhibited a significantly lower suppressive nTreg activity (94.4 % in young vs.16.7% suppression in elderly of CD4+TL stimulated by anti CD3 antibody). Conclusion: Our studies show that the CTL function is comparable between the two groups of patients but the nTreg activity in elderly patients is significantly reduced. More critical studies will be needed in larger number of patients to develop a comprehensive understanding of the T cell-mediated function that is important for immune based treatment of elderly melanoma patients. 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 5017. doi:10.1158/1538-7445.AM2011-5017
Incidence and prognostic impact of other cancers in a population of long-term survivors of chronic lymphocytic leukemia
Authors: L. Falchi, C. Vitale, M.J. Keating, S. Lerner, X. Wang, K.Y. Elhor Gbito, S. Strom, W.G. Wierda, A. Ferrajoli
Journal: Annals of Oncology (2016)
Bilateral Vagus Nerve Neurolymphomatosis Diagnosed Using PET/CT and Diffusion-Weighted MRI
Authors: Boasquevisque Gs, Guidoni J, Moreira de Souza LA, Gonçalves Pg, Andrade Cv, Pedras Fv, Boasquevisque Em, Boasquevisque Ets
Journal: Clinical Nuclear Medicine (2012)

In neurolymphomatosis, malignant lymphocytes infiltrate the peripheral nervous system in the presence of a known or unknown hematological malignancy. This report describes the findings of diffusion-weighted MRI and 18F-FDG PET/CT in a 65-year-old man with hoarseness. Results revealed a mass with restricted diffusion on diffusion-weighted imaging in the right visceral vascular space, increased uptake of 18F-FDG, and other masses at distant peripheral nerves. Restaging PET/CT showed involvement of the right brachial plexus and right sciatic nerve. Biopsy and immunohistochemistry of the right vagus nerve and cervical lymphadenopathy revealed a diffuse large B-cell non-Hodgkin lymphoma.
IMPACT OF LEFT ATRIAL APPENDAGE MORPHOLOGY ON PER-INTERVENTIONAL THROMBOEMBOLIC RISK DURING CATHETER ABLATION OF ATRIAL FIBRILLATION
Authors: Jedrzej Kosiuk, Sotirios Nedios, Jelena Kornej, Emmanuel Koutalas, Livio Bertagnolli, Sascha Rolf, Arash Arya, Philipp Sommer, Daniela Husser, Gerhard Hindricks, Andreas Bollmann
Journal: Journal of the American College of Cardiology (2014)
THU0579 Rheumatoid Arthritis Flares: Inflammatory or Avalanche?
Authors: C. A. Flurey, M. Morris, J. Pollock, R. Hughes, P. Richards, S. Hewlett
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Previous research has not addressed how RA patients' symptoms change daily. <h3>Objectives</h3> The aim of this research was to explore symptom patterns during daily life and flare <h3>Methods</h3> RA patients completed self-reported VAS (0-10) of pain, fatigue, swollen joints, stiffness, anger, frustration, worry and flare status (yes/no) daily for 3 months either on paper or online. This was an exploratory study and therefore not powered for statistical significance. Data were analysed for descriptive statistics and visually analysed with the use of graphs to identify symptom patterns <h3>Results</h3> 28 patients agreed to take part: 5 withdrew, 6 had missing data for &gt;10/91 days. The 17 patients included in the analysis were 15 female, mean age: 62.9yrs, disease duration: 18.6yrs, HAQ: 1.86 On plotting the symptoms onto graphs, 3 patients reported constant flare for 91 days (constant flare group), 6 patients self-reported ≥1 flare with periods of non-flare (intermittent flare group) and 8 patients did not report being in a flare (daily life group). As expected, the group means of the individual symptoms were highest in the constant flare group and lowest in the daily life group. In the daily life group, patients' individual mean pain scores ranged from 0.2 to 5.8, whereas in the intermittent flare group patients' individual mean pain scores ranged from 2.5 to 7.0 and in the constant flare group patients' individual mean pain scores ranged from 2.4 to 9.3. Thus some individual patients reported lower mean pain in flare than other patients reported on non-flare days, this was also the case with the other self-reported measures (see Table 1). Further 5/6 patients in the intermittent flare group rated their symptoms as more severe on non-flare days than on days in flare. Thus patients may be using different criteria other than symptoms to decide whether they are in a flare. Whilst many patients reported traditional 'Inflammatory Flare' of symptoms, other patients may be reporting flare based on experiencing overall loss of control in their lives and thus defining their overall disease activity as more severe (in flare) despite individual symptoms being less severe. The term 'Avalanche Flare' is proposed for this cascading effect of life. <h3>Conclusions</h3> Definitions of flare vary within and between patients and may not be defined by symptom severity alone. Clinicians need to be aware that patients use 'flare' to explain a range of experiences. Understanding the terminology is necessary to improve communication and inform treatment decisions <h3>Disclosure of Interest</h3> None Declared
SOLUCIONES DE LARGA DURACIÓN EN LA SUBMUCOSA PARA DSE COLORRECTAL: ¿EL INCREMENTO DEL COSTE APORTA ALGUNA VENTAJA?
Authors: JC Marín-Gabriel, J Díaz-Tasende, P Cancelas-Navía, S Rodríguez-Muñoz, AJ Del Pozo-García, M Pérez-Carreras, M Alonso-Riaño, F Colina-Ruizdelgado
Journal: Endoscopy (2014)

Introducción: En disección submucosa endoscópica (DSE) colorrectal se ha sugerido el uso de diversas sustancias de inyección submucosa para reducir el riesgo de perforación.
FRI0472-HPR Assessment of postural control, strenght of lower limbs and pain in individuals with and without fibromyalgia:
Authors: L.H.A. Muto, J.F. Sauer, S.L.K. Yuan, A.P. Marques
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Fibromyalgia (FM) is a syndrome characterized by chronic widespread musculoskeletal pain and the presence of tender points associated with sleep disturbance, fatigue, chronic headaches and psychiatric disorders, factors that may be associated with falls. Few studies have described the existence of a relationship between fibromyalgia and increased risk of falls. <h3>Objectives</h3> To assess the postural control (center of gravity oscillation), strength of lower limb and pain in individuals with and without FM. <h3>Methods</h3> The study included 47 women aged between 35 and 60 years old divided into two groups: Fibromyalgia Group (FG) n=25 and Control Group (CG), n=22 without FM. In order to characterize the subjects it has been used the Fibromyalgia Impact Questionnaire (FIQ) [1,2]. The postural control was assessed by mCTSIB test on the Balance Master NeuroCom System force platform, muscular strength with portable Dynamometer, pain with visual analogue scale (VAS) and pain threshold with digital algometer. A descriptive and inferential analysis of the data (t Student test, Mann-Whitney U test and significance level α =0.05) has been made. <h3>Results</h3> The FG presented higher score in QIF and higher number of positive tender points; 72% of the group reported dizziness. The FG presented worse postural control, with faster center of gravity oscillation (COG) (p=0.025), and right quadriceps maximal isisometric strength lower than the CG (p&lt;0.001), greater pain intensity (p&lt;0.001) and lower pain threshold (p&lt;0.001). <h3>Conclusions</h3> The GF presented a higher COG oscillation speed, lower limbs muscle strength decreasing, more intense pain and lower threshold. <h3>References</h3> Burckhardt CS, Clark SR, Bennett RM. The Fibromyalgia Impact Questionnaire: Development and Validation. J Rheumatol, 1991, 18: 728-33. Marques AP, Santos AMB, Assumpção A, Matsutani LA, Lage LV, Pereira CAB. Validation of the Brazilian version of the Fibromyalgia Impact Questionnaire (FIQ) Rev Bras Reumatol 2006: 24 (1): 24-31. <h3>Disclosure of Interest</h3> None Declared
Abstract 1864: Mitochondrial bioenergetics of metastatic breast cancer cells in response to decreasing oxygen tension.
Authors: Praveen K. Vayalil, Anne R. Diers, Claudia R. Olivia, Corinne E. Griguer, Victor Darley-Usmar, Douglas R. Hurst, Danny R. Welch, Aimee Landar
Journal: Cancer Research (2013)

Abstract Solid tumors are characterized by regions of low oxygen tension, which play a central role in tumor progression and resistance to therapy. The major organelle affected by reduced oxygen tension is the mitochondrion, which has to functionally adapt to maintain cellular bioenergetics for the cell survival. In the present study, a novel experimental approach was developed to examine the real-time bioenergetic changes during adaptation to various oxygen tensions ranging from 20% to &amp;lt; 1% oxygen using highly sensitive extracellular flux technology. Oxygen was gradually removed from the culture medium, and bioenergetic changes were measured in normal breast epithelial (MCF10A) and metastatic cancer cell lines (MDA-MB-231 and MCF10CA clones). We found that breast cancer cells, but not MCF10A cells, rapidly responded to low oxygen tension by stabilizing HIF-1α, increasing hypoxia responsive gene expression, and stimulating cellular uptake of glucose, confirming previous observations. In addition, breast cancer cells increased extracellular acidification rate (ECAR) or glycolysis during adaptation to low oxygen tension, and this effect was markedly lower in MCF10A cells. Interestingly, breast cancer cells exhibited a biphasic response in oxygen consumption rate (OCR) as the oxygen tension was reduced gradually from 20% to &amp;lt;1.0%, a response not previously described. This effect is HIF-1α-dependent, as silencing HIF-1α function in cancer cells completely abolished the biphasic response in OCR and increase in ECAR. Moreover, cancer cells demonstrated the ability to restore and maintain its OCR steadily at specific oxygen tension either during deoxygenation or reoxygenation, an effect not observed in HIF-1α silenced cells. Additional studies confirmed that the initial stimulation of OCR is due to increased mitochondrial respiration. In conclusion, our results suggest that HIF-1α provides high degree of bioenergetic flexibility under different oxygen tensions which may confer an adaptive advantage in the ever-changing tumor microenvironment as well as during invasion and metastasis. Moreover, these differences may be useful in screening novel therapeutic agents that target the bioenergetics of cancer cells in response to low oxygen tension. Citation Format: Praveen K. Vayalil, Anne R. Diers, Claudia R. Olivia, Corinne E. Griguer, Victor Darley-Usmar, Douglas R. Hurst, Danny R. Welch, Aimee Landar. Mitochondrial bioenergetics of metastatic breast cancer cells in response to decreasing oxygen tension. [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 1864. doi:10.1158/1538-7445.AM2013-1864
Abstract 4534: A novel and potent small molecule antagonist of HDM2, SCH 1450206, activates the p53 pathway with mechanism-based activity
Authors: Suxing Liu, Asra Mirza, Xiaoying Wang, Philip Lipari, Yinghui Lin, Stephane Bogen, Yao Ma, Ronald Doll, Gerald Shipps, Cynthia Seidel-Dugan, Daniel J. Hicklin, W. Robert Bishop, Yaolin Wang
Journal: Cancer Research (2010)

Abstract p53 is an attractive therapeutic target in oncology since aberrant regulation of p53 expression is associated with cancer development and progression. HDM2 is a primary negative regulator of p53 function in cells. The blockade of the p53-HDM2 interaction presents an attractive approach for development of drugs against tumors expressing wild-type p53. Here we report a novel and potent small molecule antagonist of HDM2, SCH 1450206. It binds selectively to the HDM2 protein with high affinity, with weak affinity to HDMX protein. SCH 1450206 induced dose- and time-dependent stabilization of p53 protein and its downstream targets in several human cancer cell lines with wild-type p53, but not in cell with p53 gene deletion. SCH 1450206-induced stabilization of p53 led to distinct changes in expression of p53 target genes regulating apoptosis and cell cycle checkpoints. Inhibition of cell proliferation and induction of apoptosis were surveyed in a panel of human tumor cell lines following SCH 1450206 treatment. Inactivation of p53 by shRNA in cell lines expressing wt-p53 abolished the inhibition of cell proliferation and appearance of senescence in response to SCH 1450206, suggesting the cellular activity of SCH 1450206 is p53 specific and mechanism-based. Taken together, our results demonstrated the mechanism of action of SCH 1450206, a novel HDM2 antagonist that can activate the p53 pathway, and offers a potential anti-tumor agent targeting tumors expressing wild-type p53. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4534.