tbuckley/cabot-search huggingface dataset:
A2.34 Anti-inflammatory effects of vitamin D are reduced in T-cells from the inflamed joints of rheumatoid arthritis patients
Authors: LE Jeffery, P Henley, M Hewison, A Filer, DM Sansom, K Raza
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background and objectives</h3> Low serum vitamin D associates with chronic inflammatory diseases such as rheumatoid arthritis (RA), thus vitamin-D supplementation has been suggested for their treatment. T-cells have a pathogenic role in RA. We have shown that active vitamin-D, 1,25-dihydroxyvitamin D<sub>3</sub> (1,25(OH)<sub>2</sub>D<sub>3</sub>), has potent anti-inflammatory effects on T-cells. However the efficacy of vitamin-D in an inflammatory setting is unclear. This study was designed to assess the effect of 1,25(OH)<sub>2</sub>D<sub>3</sub> upon inflammatory responses by CD4<sup>+</sup>T-cells from the blood and synovial fluid (SF) of RA patients. <h3>Methods</h3> Ethical approval was granted by Solihull Research Ethics Committee. Patients who fulfilled 1987 ACR criteria for RA and age-matched healthy controls were recruited with informed consent. CD4<sup>+</sup>T-cell responses to 100nM 1,25(OH)<sub>2</sub>D<sub>3 </sub>were assessed by flow cytometry after stimulation. Mononuclear cells from blood and SF were stimulated with antiCD3 and magnetically isolated naïve (CD45-RA) and memory (CD45-RO) CD4<sup>+</sup>T cells were stimulated with monocytes+antiCD3. Regulators of 1,25(OH)<sub>2</sub>D<sub>3</sub>signalling were measured in purified T-cells by qPCR before and after stimulation with antiCD3/CD28 beads. Significance was tested by Wilcoxon analysis. <h3>Results</h3> 1,25(OH)<sub>2</sub>D<sub>3 ­</sub>significantly reduced IL-17 and IFNy production by T-cells from the blood of RA patients and healthy controls. By contrast, SF T-cells from RA patients<sub>,</sub> showed reduced suppression of IL-17 by 1,25(OH)<sub>2</sub>D<sub>3</sub> and no inhibition of IFNγ. 98(±1.8)% of SF T-cells were memory compared to 49(±14)% for blood. Unlike SF T-cells, 1,25(OH)<sub>2</sub>D<sub>3 </sub>suppressed IFNγ production by memory T-cells from blood. However across several targets: IL-17, IFNγ, IL-21, CTLA-4 and FoxP3, naive cells showed greater sensitivity than memory cells to 1,25(OH)<sub>2</sub>D<sub>3</sub>. Interestingly, the vitamin D receptor (VDR) was elevated in SF memory T-cells compared to equivalent cells from blood, suggesting that lack of VDR does not explain the diminished responsiveness of SF T-cells. Furthermore, stimulation, increased VDR, RXR and the VDR co-enhancer/co-repressor ratio to similar levels in T-cells from both sites and suppressed their expression of the 1,25(OH)<sub>2</sub>D<sub>3</sub>-inactivating enzyme, CYP24A1 equally. <h3>Conclusion</h3> Stimulation primes CD4<sup>+</sup>T-cells from RA patient blood and SF to respond to 1,25(OH)<sub>2</sub>D<sub>3</sub>. However, SF T-cells are less sensitive to 1,25(OH)<sub>2</sub>D<sub>3</sub>. This is only partially explained by their shift to memory status. Such insensitivity of joint T-cells to 1,25(OH)<sub>2</sub>D<sub>3</sub> has important implications regarding the use of vitamin D to treat RA.
Successful use of Hemospray to control refractory duodenal diverticular bleeding
Authors: Christian Dietrich, Rico Hochdörffer, Erik Fuchs, Stephan Vetter, Ralf Jakobs, Matthias Bechtler
Journal: Endoscopy (2014)

A 78-year-old woman, on rivaroxaban medication because of atrial fibrillation, was referred to our department with upper gastrointestinal bleeding. Emergency esophagogastroduodenoscopy (EGD) revealed multiple duodenal diverticula with oozing bleeding from inside a large diverticulum near the papilla ([Fig. 1] and [Fig. 2]). Because of the location, clips were not applicable, hence injection of epinephrine and later injection of fibrin glue were administered. In spite of these interventions, signs of bleeding recurred. On the third day after admission, 10 g of Hemospray was applied into the descending duodenum using a 10-Fr catheter ([Fig. 3] and [Fig. 4]). After several bursts of Hemospray, bleeding stopped. During control examination 1 day later, Hemospray had disappeared from the gastrointestinal tract, but bleeding from the duodenal diverticulum had recurred. The remaining Hemospray was applied into the diverticulum and bleeding subsided. An overview of hemoglobin level, endoscopic interventions, and transfusions is shown in [Fig. 5]. Follow-up EGD 2 days later was unremarkable and the patient resumed an oral diet. After discharge, no further bleeding occurred during a 30-day follow-up.
Abstract 1597: A novel preclinical model of prostate cancer bone metastasis derived from a human primary tumor
Authors: Nader Ainakouzi, Olivia Bawa, Paule Opolon, Stephanie Lerondel, Alain Lepape, Catherine Gaudin, Christophe Massard, Yohann Loriot, Karim Fizazi, Anne Chauchereau
Journal: Cancer Research (2011)

Abstract Background: Prostate cancer is frequently associated with bone metastases which are the main cause of morbidity and mortality for this tumor. Animal models are important tools to investigate the pathogenesis and develop treatment strategies for bone metastases in humans. However there are few animal models that recapitulate spontaneous clinical bone metastases. We recently obtained the new prostate cell line IGR-CaP1 derived from primary epithelial prostate cancer that has been characterize in vitro. Methods: The IGR-CaP1 cell line was stably transduced with a luciferase expressing viral vector to monitor tumor growth by bioluminescence imaging (BLI) in male nude mice. Bone lesions were observed after direct intratibial injections of 5×105 luciferase-expressing IGR-CaP1 cells and after injection of 106 cells into the left cardiac ventricle of mice. Bone metastases were detected by bioluminescence imaging and were evaluated by both Computerized Tomography (CT) and micro Single-Photon Emission Computed Tomography (SPECT) measuring the bone fixation of 99Tc methylenediphosphonate (m99Tc-MDP). Results: In contrast with the widely used PC3 preclinical model showing only osteolytic activity after bone injection, high resolution CT scan showed both lytic lesions in the cortical bone and osteoblastic lesions in the trabecular bone in the IGR-CaP1-injected mice 5 weeks after injection. The mixed nature of the lesions and the intensive bone remodeling were confirmed by bone scintigraphy with a ∼5 fold increase in m99Tc-MDP fixation in injected tibia versus control tibia. Intracardiac injection led to bone metastasis mainly localized in the spinal column, fore and hind limbs and in the mandible. Immunohistochemistry confirmed the presence of these bone metastases and showed high expression of vimentin in metastatic tumor cells. In this model, we are currently analyzing by RT-PCR, the expression of a 25-gene signature that corresponds to genes highly expressed in human bone metastases. Conclusion: IGR-CaP1 is a unique model issued from a primary tumor able to reconstitute human prostate adenocarcinoma in animals and provide bone metastases. This model provides a novel means for identifying and understanding mechanisms that contribute to bone metastasis and allows for preclinical testing of new anticancer therapies, specifically bone-targeting therapies. 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 1597. doi:10.1158/1538-7445.AM2011-1597
THE PREDICTION OF HUNTINGTON'S CHOREA
Authors: RALPH M. PATTERSON, B. K. BAGCHI, AVERY TEST
Journal: American Journal of Psychiatry (1948)

Twenty-six offspring representative of 9 families with Huntington's chorea in the immediate ancestry were subjected to the following studies: physical, neurological, psychiatric, psychometric, anthropometric, genetic, and electroencephalographic. Of these various procedures, but 2 seemed to offer probable predictive value: namely, the EEG and the blood groupings. Nineteen, (73.1%) of the subjects showed definite electroencephalographic abnormalities, particularly in the motor regions. Bilateral paroxysmal bursts like those observed in epilepsy were found in the resting record of about half (8) of the cases showing abnormal EEGs. According to a composite weight, 12 offspring had the highest electroencephalographic abnormality and were thought likely to develop the disease as this proportion approximated the genetic probability. No definite intra- or inter-family, or parent-offspring, electroencephalographic resemblances were noted. The study of blood groupings was expanded to include all available cases of Huntington's chorea in addition to the offspring study and disclosed a disproportionately large number of individuals in Groups A and O. Longrange follow-ups with repeated EEGs on a larger series of offspring are recommended as well as a much more extensive examination of the blood groupings of Huntington's chorea patients and their offspring in order to establish the statistical validity of the 2 procedures.
Abstract 4087: Metabolic changes associated with acquired cisplatin resistance
Authors: Elizabeth J. Sullivan, Metin Kurtoglu, Medhi Wangpaichitr, Niramol Savaraj, Theodore Lampidis
Journal: Cancer Research (2011)

Abstract Although cisplatin is the drug of choice in treating lung cancer patients, acquired resistance appears to be a common and serious drawback to its effectiveness in the clinic. Using two pairs of cisplatin sensitive and resistant lung cancer cell lines developed in vitro, we have found significantly lowered hexokinase II (HKII) levels in both resistant cell lines. As a consequence of lowered HKII, these cell lines, when grown under anaerobic conditions, are markedly more sensitive to the glycolytic inhibitor 2-deoxy-D-glucose (2DG) than their parental cell lines from which they were derived. This was our first indication that lowered HKII levels in these cisplatin resistant cells has metabolic consequences in different environmental conditions. Thus, it appears that a fundamental difference in glucose metabolism is associated with resistance to cisplatin in these cell lines. It is the aim of this study to explore whether reduced HKII is a common occurrence in cisplatin resistant cells and whether these differences uncover metabolic targets that can be exploited for therapeutic gain. Much like the Atkins diet, when carbohydrates are lowered or glycolysis is inhibited, other sources of energy such as fatty acids and amino acids can be used to maintain cell viability. A trypan blue cytotoxicity assay was used to determine the sensitivity of our cisplatin resistant cell lines to a pharmacological inhibitor, etomoxir, toward fatty acid oxidation. Thus, we tested and found that one of these cisplatin resistant cell lines is sensitive to interference with fatty acid oxidation. Next, we placed our cell lines in glutamine free medium, and found that the second cisplatin resistant cell line is sensitive to glutamine deprivation. Moreover, when lactate production was measured in anaerobic conditions, cisplatin resistant cell lines produced less lactate when challenged with the glycolytic inhibitor, 2DG, than their cisplatin sensitive parental cell lines. Overall, our results indicate that lowered HKII levels in two cisplatin resistant cell lines appear to be associated with a decreased reliance on glucose metabolism, with a shift to either fatty acid oxidation or glutaminolysis. Moreover, these cisplatin resistant cells are sensitive to glycolytic inhibition when placed in oxygen-deprived conditions. Thus, these new metabolic targets may be exploited for therapeutic gain in the clinic. 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 4087. doi:10.1158/1538-7445.AM2011-4087
Loss of fractured part of a proximally migrated esophageal stent through vomiting
Authors: R. Gomes, S. Nagral, P. Agarwal
Journal: Endoscopy (2012)

Placement of self-expanding, covered metal stents is the first choice of management in the palliative therapy of unresectable esophageal cancer. These stents have a much higher rate of stent migration (27 % compared with 8.7 % of uncovered stents), and migration occurs more often at the gastroesophageal junction as the distal part of the stent is not fixed to the esophageal wall and projects freely into the lumen[1].
Abstract 1051: Quantitative assay for simultaneous assessment of phosphorylation and cell migration
Authors: Michael Olive, Huaxian Chen
Journal: Cancer Research (2010)

Abstract Introduction: Cell migration is a critical process in angiogenesis and inflammation as well as tumor progression and metastasis. The acquisition of the ability to migrate is dependent on the activation of key cell signaling pathways, two of which are modulated by AKT and ERK kinases. Screening assays that can simultaneously quantify cell migration and the activity of the underlying signaling kinases may facilitate more efficient identification of therapeutic compounds. Methods: Oris™ Cell Migration Assay plates (Platypus Technologies, Madison, WI) were seeded with HT1080 cells. The Oris plates contain a stopper, which when removed following 24 h cell growth, creates a defined cell-free region on the plate. After removal of the stoppers, PI3 kinase and MEK inhibitors were added and cells allowed to migrate. After fixing and permeabilization, cell migration was measured by staining with primary mouse antibodies against total ERK2 and histone H3, application of a plate-specific mask that allowed detection of only migratory cells, and quantification by staining with IRDye 680-labeled goat anti-mouse antibodies. Phosphorylation was measured simultaneously by staining with rabbit antibodies against either phospho-AKT or phospho-ERK and detection with IRDye 800CW-labeled goat anti-rabbit antibodies. Fluorescence was detected by scanning with either an Aerius or Odyssey instrument. Results: AKT and ERK phosphorylation were specifically inhibited by their respective drugs. The level of inhibition of phosphorylation correlated with decreased migration in a dose-dependent manner. The robustness of the assay was exemplified by its high signal to noise ratio. Conclusions: Anti-cancer drugs developed by assessment phosphorylation state alone may identify hits that inhibit the target kinase, yet fail to retard functional outcomes such as migration and proliferation. We have designed a quantitative assay that allows for simultaneous assessment of a biochemical characteristic, namely phosphorylation state, and a functional parameter related to metastasis. This quantitative assay may facilitate a better understanding of the mechanisms underlying cell movement and metastasis, and may facilitate a more efficient means of developing anti-cancer drugs. 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 1051.
QL-10 * NEURO-ONCOLOGY TELEMEDICINE FOLLOW-UP VISITS
Authors: R. Green, E. Woyshner
Journal: Neuro-Oncology (2014)

We report our 18 month experience with the use of a videoconferencing system to perform neuro-oncology follow-up visits. The Neuro-oncology Program at the Kaiser Permanente-Los Angeles Medical center serves the majority of Kaiser HMO patients in the Southern California region. We installed a videoconferencing system (Cisco TelePresence EX90, Cisco Systems, San Jose, CA) in our office in Los Angeles and in a medical office building in Anaheim, CA at a distance of 35 miles. Established neuro-oncology patients from Orange County chose between in-person and remote visits. Patients were seated in an examination room and the neuro-oncology provider alerted by text page. A focused history and physical examination was performed, followed by desktop sharing of clinical and laboratory data using an electronic medical record (Epic Systems Corporation, Verona, WI) and of neuroimages (Phillips iSite PACS, Andover, MA). Patients were asked, but not required, to complete an anonymous online 16 question satisfaction survey after each visit. Visits were performed by either a neuro-oncologist (179) or a Physician's Assistant (12). Of the 191 visits, 174 included evaluation of neuroimaging and 77 included evaluation of response to ongoing chemotherapy. During 12 visits chemotherapy was initiated, and during 15 visits the chemotherapy regimen was changed based on imaging findings. One-hundred and eleven surveys (58% of visits) were completed. Patients reported a high level of satisfaction with the visits (average 9.6, on a 1-10 scale). The average estimated travel time saved was 118 minutes per visit. Four surveys reported technical problems and 1 indicated a preference for an in-person visit. No adverse events could be attributed to use of the telemedicine system. These data suggest that neuro-oncology follow-up visits can be practiced safely and effectively using a telemedicine system, with high levels of patient satisfaction.
Abstract P3-12-08: Incidence, predictive factors and outcome of brain metastases (BM) in a single institution cohort of breast cancer patients.
Authors: A Perelló, J Alarcon, C Garcias, J Duran, B Colom, G Clemente, A Avella, R Canet, J Torrecabota, J Rifa
Journal: Cancer Research (2012)

Abstract Background: The aim of the study was to determine the cumulative incidence of BM, predictive factors of BM, and survival from diagnosis of BM in a cohort of breast cancer patients in a single institution. Patients and Methods: We collected data from a cohort of 793 breast cancer patients between January 2000 and December 2005 in our institution. Variables recorded include age at diagnosis, hormonal receptor status (HRS), human epidermal growth factor receptor 2 status (HER2), histological grade, T stage and N stage. We analyzed the 5 and 10-year cumulative incidence of BM. Time to detection of BM and survival from BM were estimated using Kaplan-Meier method. Cox regression model was used to analyze the variables associated with time to BM Results: With a median follow-up of 100 months, 49 patients went on to develop BM. The overall 5 and 10 year cumulative incidence of BM were 4.9% and 8.2% respectively. The table shows the 5 and 10 year cumulative incidence and hazard ratio (HR) of the predictive factors for the development of BM in the univariable analysis. Including all significant variables in the model, HER2 positive and node positive patients had an increase risk of BM, HR 2.46 (95% CI: 1.22–4.95) and 2.51 (95% CI: 1.19–5.29) respectively. HRS positive patients had a decreased risk of developing BM, HR 0.44 (95% CI: 0.21–0.89). Median survival from BM of HER2 positive and HER2 negative patients was 9 and 3 months respectively (p = 0.015), and 6 and 1 month for HRS positive and negative respectively (p = 0.02) Conclusion: Predictive factors independently associated with a high risk of BM in our cohort are HER2 positivity and positive nodes. Patients with positive HRS have a decreased risk of BM. Survival time following BM is poor. HER2 positive and HRS positive patients have a better survival than HER2 negative and HRS negative patients. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-12-08.
Multiple-Gated Acquisition Scan With Normal Left Ventricular Ejection Fraction and LBBB
Authors: Lorenzo Mannelli, James H. Caldwell, Shana Elman, David H. Lewis, Bernard W. Do, Hubert Vesselle
Journal: Clinical Nuclear Medicine (2013)

Multiple-gated blood pool angiography (MUGA) using 99mTc-UltraTag (Mallinckrodt Inc., Maryland Heights, MO) labeled RBCs was performed in a patient with B-cell lymphoma for evaluation of the left ventricular ejection fraction before starting chemotherapy. Quantitative measurements from MUGA demonstrated normal left ventricular ejection fraction. However, cine images revealed delayed contraction of the left ventricle compared with that of the right, and phase contrast images demonstrated offset of the ventricles' phases. Evaluation with ECG showed delayed depolarization of the left ventricle consistent with LBBB. Phase imaging abnormalities detected on MUGA may be overlooked. Specific patterns of phase abnormalities may direct the physicians' attention toward yet unrecognized diagnoses.
Abstract 4309: DYRK2 regulates cancer invasiveness via Snail/E-cadherin pathway
Authors: Rei Mimoto, Naoe Taira, Kiyotugu Yoshida, Yoshio Miki
Journal: Cancer Research (2012)

Abstract Epithelial-mesenchymal transition (EMT) is characterized by the loss of cellular adhesion molecule E-cadherin, and plays a fundamental role during early steps of invasion and metastasis. An important regulator of E-cadherin expression is Snail, a zinc-finger transcriptional repressor. Snail is phosphorylated by GSK3-α and then degraded by α-TrCP-mediated ubiquitination. Here we describe another kinase, DYRK2, acts as a priming kinase for snail whose phosphorylation is required for the subsequent GSK3&amp;gamma phosphorylation and proteasomal degradation. Inhibition of DYRK2 expression by siRNA results in up-regulation of Snail and down-regulation of E-cadherin. The expression of fibroblast mrakers, vimentin and fibronectin, emerged in these cells. Furthermore, the invasiveness of MCF7 cells was increased by stable DYRK2 silencing by shRNA. Tumors expressing DYRK2-shRNA robustly formed metastases in nude mice bones, while those expressing control-shRNA little if any. In human breast cancer tissues, DYRK2 exhibits an inverse correlation with the expression of Snail. Conversely, low level expression of DYRK2 is associated with down regulation of E-cadherin. The patiens with tumors expressed low DYRK2 showed significantly poor prognosis and short disease-free survival. These results demonstrate that DYRK2 regulates cancer invasiveness and metastasis via Snail/E-cadherin pathway in human breast cancer. 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 4309. doi:1538-7445.AM2012-4309