tbuckley/cabot-search huggingface dataset:
Abstract 4278: Spheroid growth in 3D alginate matrices
Authors: John Michael Dornish, Therese Andersen, Helene Heier-Baardson, Christine Markussen, Carol Ward, Peter Mullen, Simon Langdon, Ian Kunkler, David Harrison
Journal: Cancer Research (2011)

Abstract The use of 3-dimensional (3D) matrices for cell culture is gaining popularity as a substitute for traditional 2D cell culture as it can approximate cell architecture and cell-cell contact found in tissues, organs and tumors. NovaMatrix-3D™ is an alginate-based cell culture system comprising an alginate foam matrix and an alginate immobilizing solution. In principle, cells are first suspended in a sodium alginate solution then the cell suspension is applied to the alginate foam. In situ gelation occurs when calcium ions are donated from the foam cross-linking the added alginate, effectively entrapping the cells within the pores throughout the foam. To show the utility of the NovaMatrix-3D™ culture system, various cell lines were first cultured in 2D then prepared as a suspension in 0.5 – 1% sodium alginate in cell culture medium. An aliquot of each cell suspension was added to γ-sterilized NovaMatrix-3DTM foams (12- or 24-well plate size). NHIK 3025 (cervix carcinoma), MCF7 (breast adenocarcinoma), ZR-75-1 (breast ductal carcinoma) and NIH:OVCAR-3 (ovarian adenocarcinoma) were used and single cells were immobilized in the alginate foams. Cell localization within the foam was visualized using confocal microscopy to identify fluorescently labeled (CellTrace™ CFSE) cells. Cell proliferation was measured by counting cells after de-gelling the foam using sodium citrate. In each case, cells were immobilized with or without RDG-coupled alginate to investigate the importance of the presence of cell attachment peptides within the alginate. For these cell lines, cell growth and multicellular spheroid formation was independent of the presence of RGD. Spheroids could also be removed intact by de-gelling the alginate matrix and further processed for histological staining. One example shows the selective staining of apoptotic cells within the spheroid. Use of alginate foams with concomitant in situ immobilization of cells results in a 3D cell culture model with the potential to approximate cell proliferation and architecture within tissues or tumors. The technology enables biomimetic approaches by varying e.g. matrix elasticity, gelling ions, attachment peptides and foam degradation making NovaMatrix-3D™ a versatile cell culture system. Portions of this work have been funded with the support from METOXIA project no.222741 under the 7th Research Framework Programme of the European Union. 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 4278. doi:10.1158/1538-7445.AM2011-4278
Rates of Rebound or Relapse Among Acute Attacks of Hereditary Angioedema Treated with Ecallantide in Open-Label, Repeat-Treatment Study
Authors: H.H. Li, J.A. Bernstein, D.F. Soteres, M. Riedl, W.R. Lumry, T.J. Craig, A.J. MacGinnitie, R. Iarrobino, Y. Chyung, E.P. Shea, W.E. Pullman
Journal: Journal of Allergy and Clinical Immunology (2012)
A1.22 Interleukin-1 does not aggravate joint inflammation and cartilage destruction in experimental osteoarthritis
Authors: SCM van Dalen, AB Blom, LAB Joosten, AW Slöetjes, MMA Helsen, WB van den Berg, PLEM van Lent
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background and objectives</h3> Osteoarthritis (OA) is a degenerative joint disease characterised by severe cartilage destruction, with a putative role for synovial macrophages. Recently it has become clear that over 50% of the patients also show low grade joint inflammation reflected by a thickened synovial lining and elevated production of cytokines like interleukin-1 (IL-1)by different cell types in the synovium. IL-1 mediates cartilage destruction by degrading existing proteoglycans and inhibiting new formation ofproteoglycans by stimulating degradative enzyme production. However, treatment of OA patients with IL-1 inhibitors has so far been disappointing. In this study we investigated the role of IL-1α/β in synovitis and cartilage destruction during experimental collagenase-induced OA (CiOA). <h3>Materials and methods</h3> Experimental OA was induced by intra-articular injection of collagenase into WT and IL-1αβ<sup>-/-</sup> mice. At day 7 after CiOA induction, total knee joints were stained with haematoxylin/eosin (H&amp;E) to score synovial activation (arbitrary score from 0–3). Cartilage destruction at day 7 and 42 after induction of CiOA was determined in knee sections stained with safranin O/fast green using a modified Pritzker score. Gene expression in inflamed synovium was analysed using qPCR with primers for several pro- and anti-inflammatory cytokines. <h3>Results</h3> Synovitis in IL-1αβ<sup>-/-</sup> mice at day 7 of CiOAwas not different from WT controls (2.9 ± 0.2 and 2.7 ± 0.4 respectively). Absence of IL-1α/β had no effect on synovial mRNA levels of pro-inflammatory mediators KC, S100A8 and S100A9. IL-6 mRNA levels, however, were significantly down-regulated in the synovium of IL-1αβ<sup>-/-</sup> mice (3-fold reduction). The lack of IL-1α/β also did not affect gene expression of anti-inflammatory cytokines IL-10, TGFβ and iNOS. Cartilage destruction in CiOA clearly aggravated over time. Cartilage lesions in IL-1αβ<sup>-/-</sup> mice were not significantly different from WT controls at day 7. Also no difference in cartilage damage was measured at day 42 of CiOA when compared to WT (at the medial femur (95.3 ± 42.0 vs. 65.5 ± 54.5), medial tibia (84.5 ± 36.6 vs. 55.1 ± 38.9), lateral femur (69.6 ± 43.9 vs. 60.8 ± 35.8), and lateral tibia (49.8 ± 26.3 vs. 55.4 ± 17.1)). <h3>Conclusions</h3> IL-1β does not affect synovial inflammation nor cartilage destruction during collagenase-induced osteoarthritis, implicating that other macrophage-derived mediators are responsible for the joint damage.
AB0172 Assessment of disease activity in rheumatoid arthritis by routine assessment of rheumatoid arthritis disease activity index (radai) and its relation with disease activity score 28 (das28), clinical disease activity index (cdai) and simplified disease acti
Authors: F. Kaygisiz, P. Borman, F. Tuncay, M. Okumus, R. Erdem
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Evaluation of disease activity is essential in decision of the treatment and monitoring the therapies in rheumatoid arthritis (RA). Rheumatoid Arthritis Disease Activity Index (RADAI) appears as an attractive form in determining the disease activity in RA patients especially in busy clinical settings, as it comprises current and past disease activity and morning stiffness. <h3>Objectives</h3> The aim of this study was to evaluate the disease activity by RADAI and determine the correlation to other disease activity indexes like Disease Activity Score 28 (DAS28), Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI). <h3>Methods</h3> Ninty-seven Turkish patients with RA were recruited from the PMR clinic, and demographic characteristics were recorded. The clinical and laboratory parameters including joint count, health assesment questionnaire (HAQ), ESR and CRP. All patients completed the activity forms comprising RADAI, CDAI, SDAI and DAS 28. <h3>Results</h3> Ninty-seven patients with a mean age 3.86±11.03 and disease duration of 15.7±14.8 years respectively, were included. The mean scores of RADAI, CDAI, SDAI and DAS 28 were 2.4±1.9, 9.6±7.1, 10.2±7.3 and 2.8±0.9 respectively. According to RADAI assessment there were 4 patients on moderate activity,28 patients on low activity and 65patients on remisison. The percentage of patients with high/moderate/low/remission according to CDAI, SDAI and DAS28, were 4.1%/32.9%/42.2%/20.6%; 0/12.3%/63.9%/23.7%; and 0/29.8%/27.8%/42.2%, respectively. The most correlated index with RADAI was determined as CDAI (p&lt;0.05, r=0.791) and SDAI (p&lt;0.05, r=0769). <h3>Conclusions</h3> The RADAI scores provide comparable and similar quantitative information to CDAI, SDAI and DAS28 in a group of Turkish RA patients. We suggest this comprehensive assessment index especially in disease evaluation over time in RA patients' management. Also we hope our data help to make comparisons between RA patients from different cultures. <h3>Disclosure of Interest</h3> None Declared
O9.10 * ANTI-EPILEPTIC TREATMENT IN GLIOMA, A NORWEGIAN POPULATION-BASED STUDY
Authors: K. M. Knudsen-Baas, T. B. Johannesen, A. Engeland, B. A. Engelsen, A. M. Storstein, J. F. Owe
Journal: Neuro-Oncology (2014)

INTRODUCTION: Symptomatic epilepsy in glioma is traditionally perceived as difficult to treat and refractory to monotherapy. Older AEDs that induce or inhibit CytP450 enzyme systems (enzyme-inducing AED= EIAED) have previously been preferred. There is an increasing focus on the risk of interaction with other drugs with hepatic metabolism. We wanted to study whether newer AEDs with little or no enzyme effect (non-EIAED) are favored in the current treatment of epilepsy in glioma. MATERIALS AND METHODS: We identified all glioma patients with epilepsy in Norway by linking the Cancer Registry of Norway (CRN) and the Norwegian Prescription Database (NorPD). CRN has since 1952 registered information on all neoplasms diagnosed in Norway, and reporting is mandatory by law for clinicians and pathologists. NorPD was founded in 2004 by the Norwegian Institute of Public Health, and includes information on all prescriptions dispensed from all Norwegian pharmacies. We included all patients with glioma grade II-IV who were registered in NorPD. Epilepsy was defined as being registered as taking AEDs under a relevant epileptic diagnostic code. RESULTS: In 2004-2010, CRN registered 2583 patients with glioma grade II-IV, 1477 men and 1106 women. In low grade glioma, 65% had epilepsy and in high grade glioma, 47% had epilepsy. Low grade gliomas with epilepsy were localized in the frontal lobe in 46%. High grade gliomas with epilepsy were localized in the frontal lobe in 28% and the temporal lobe in 27%. In monotherapy or with other AEDs, carbamazepine was used by 34% and valproate by 36% of the 1104 patients with glioma and epilepsy. Patients aged 20-49 years with astrocytoma, and 40-79 years with glioblastoma multiforme (GBM), used non-EIAEDs more frequently than EIAEDs. Levetiracetam was the preferred AED, used by 39% of the 1104 patients. DISCUSSION: The non-EIAED levetiracetam was the most frequently used AED in glioma patients, especially in GBM. GBM patients often have overall survival <1 year and side effects of AEDs are particularly important. Levetiracetam can give cognitive side effects as mood changes or depression, reducing quality of life. Some studies have indicated an anti-tumor effect of valproate and levetiracetam. In this study, we are investigating whether the usage of different AEDs affect overall survival in GBM patients. CONCLUSION: In the Norwegian population 2004-2010, 65% of patients with low grade gliomas and 47% of patients with high grade gliomas had epilepsy. Levetiracetam was the most frequently used AED, especially in GBM. We further investigate the influence of exposure to the separate AEDs on overall survival in the GBM patients, and these results are to be presented.
Abstract 3963: Wnt-Signaling regulates angiogenesis by regulating Neuropilin-1 expression in osteosarcoma
Authors: Samia Ghaffar, Yi Guo, Peter McQueen, Alex Christ, Khoa Tu, Jun Xie, Xiaolin Zi, Bang Hoang
Journal: Cancer Research (2010)

Abstract Purpose of Study: To investigate the role of the Neuropilin-1 (NRP-1) in angiogenesis and regulation by Wnt-signaling pathway in osteosarcoma (OS) cell lines. Methods: In vitro tube formation assay using HUVEC cells to examine the effect of Frzb, WIF1, and DKK3 on angiogenesis. Microarray and real-time PCR to assess the mRNA level of NRP-1 in SaOS-2 cells transfected with Dominant Negative LRP5 (DNLRP5) and PcDNA vector control. Western blots were performed to evaluate the expression of NRP-1 in 8 OS cell lines and normal osteoblast (NHOst), as well as the effect of Wnt inhibitors (DNLPR5, Frzb, WIF-1, DKK3) on NRP-1 expression in OS cell lines (LM7, 143B, and 143.98.2) Results: In order to develop a new therapeutic target for OS, the most common primary malignant bone tumor, we examined the expression of NRP-1 and vascular endothelial growth factor (VEGF) in 8 established OS cell lines, as well as NHOst. Both VEGF and NRP-1 (a co-receptor of VEGF) were up-regulated in most OS cell lines compared with normal osteoblast, suggesting that VEGF and NRP-1 may be responsible for the excessive blood vessel formation in OS. Given our previous report that Wnt inhibitors Frzb, WIF1, DKK3, and DNLRP5, inhibited tumor growth and metastasis of OS, we hypothesize that one of the potential mechanisms may be through inhibition of tumor angiogenesis. When HUVEC assay was examined, DKK3, Frzb, WIF-1 condition medium significantly inhibited tube formation compared with control, suggesting that these Wnt inhibitors suppressed angiogenesis. Further microarray assay, real time PCR and western blots indicated that these Wnt inhibitors (DKK3, Frzb, WIF-1 and DNLRP5) dramatically down-regulated the expression of NRP-1, but VEGF level remained unchanged. These results show that inhibition of angiogenesis by Wnt signaling may be mediated by down-regulation of NRP-1 instead of VEGF. Discussion and Conclusions: Our study suggests that the Wnt-signaling reduces tumor growth and metastasis by inhibiting angiogenesis and by down-regulating NRP-1 expression in OS. We are further studying the role of NRP-1 in osteosarcoma by knockdown of NRP1 expression in OS cells to assess tumor proliferation, metastases and angiogenesis. This may represent a novel therapeutic strategy for osteosarcoma. 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 3963.
DIRECT ANATOMIC COMPARISON OF TC-99M D.L HMPAO SPECT WITH CT AND MR.
Authors: H. Dickson, K. Cooper, B. Engelstad, K. Laxer, J. Huberty, D. White
Journal: Clinical Nuclear Medicine (1987)

Dickson, H.; Cooper, K.; Engelstad, B.; Laxer, K.; Huberty, J.; White, D. Author Information
Cytomegalovirus genetic variability and the humoral immunity
Authors: Malgorzata Wisniewska-Ligeir, Wieslawa Wroblewska, Edyta Paradowska, Miroslawa Studzinska, Patrycja Suski, Zbigniew J. Lesnikowski, Teresa Wozniakowska-Gesicka
Journal: Journal of Infection (2011)
Inter-regional recruitment of melanoma families in Italy
Authors: P. Queirolo, S. Gliori, M. Acquati, L. Pastorino, M. Barile, G. Bianchi Scarrà, R. Rosso
Journal: Journal of Clinical Oncology (2005)

7528 Background: Due to the low incidence frequency of melanoma in Italy, recruitment of cases and kindreds through individual centers generally yields small numbers. We have therefore initiated an inter-regional project on melanoma genetics in Italy. This project is comprised of a retrospective population-based study of incident melanoma cases registered by several IARC-certified cancer registries (1995–1999) and of a second study that focuses on melanoma kindreds to provide a picture of melanoma families in our country as a whole, and to establish genotype/phenotype correlations using standardized phenotyping methods. Methods: Recruitment of families started in January 2004. The groups are contributing differently, according to their expertise and facilities: some recruit families, phenotype them and conduct molecular testing; others only recruit and phenotype the families and send their DNA samples to our laboratory in Genoa. Another expected source of familial cases will be the cancer registries: if there are no local facilities for genetic counseling and testing, cases are sent to Genoa. Results: Through these cooperative efforts, we have found that 37% kindreds are mutation-positive and that the frequency of founder mutations is 82.2%. The frequency of CDKN2A mutation in Liguria appears to be roughly similar to nationwide figures: 35% of the families are mutation-positive, with most carrying the G101W founder mutation. Recently we have identified another recurrent mutation, E27X, in 6 kindreds sharing a common 9p21 haplotype. We are currently studying the origin and spread of this mutation. Conclusions: The frequency of CDKN2A mutations in Italian melanoma kindreds appears to be higher than in other countries, mostly accounted for by founder mutations. This genetic homogeneity allows us to conduct targeted studies of mutation-specific penetrance and of genetic and environmental risk modifiers. It will facilitate genotype/phenotype correlations regarding the risk of developing other primary malignancies, with the overall aim of providing targeted follow-up to at-risk patients. No significant financial relationships to disclose.
Abstract P5-07-02: Analysis of a novel synergistic relationship between the FK506 binding protein FKBP52 and beta catenin in androgen receptor signaling pathways
Authors: CL Storer, K Olivares, RJ Fletterick, P Webb, MB Cox
Journal: Cancer Research (2012)

Abstract Hormone-dependent cancers depend largely on folding and regulation by a chaperone-steroid receptor complex. The final stage of the receptor-chaperone complex consists of a receptor, a heat shock protein 90 (Hsp90) dimer, p23, and an immunophilin. Hormone-dependent prostate cancer progresses due to key interactions between the androgen receptor complex and the ligand dihydrotestosterone. While current treatments block androgen receptor-ligand interactions, these therapies are no longer effective in advanced stage, hormone independent prostate cancer (HRPC), when the receptor is activated even in miniscule levels of hormone. Therefore, we are interested in targeting other members of the androgen receptor complex and signaling cascade, namely the immunophilin FK506 binding protein (FKBP52) and the Wnt cell signaling protein β-catenin. FKBP52 has the ability to potentiate activity of the androgen, progesterone, and glucocorticoid receptors and is a prostate cancer biomarker. β-catenin is a member of the cellular adhesion complex with E-cadherin in healthy cells, but in aberrant situations, β-catenin actively promotes progression and invasion in a number of cancers. Our data from FKBP52 knockout mouse embryonic fibroblast cell lines suggests that FKBP52 and β-catenin work in tandem to synergize androgen receptor (AR) transcriptional activity with the probasin promoter. When AR, FKBP52, and β-catenin are co-transfected, a synergistic up-regulation of AR signaling is observed, as assessed by luciferase reporter assays. According to pull down assays, FKBP52 and β-catenin can interact in the absence of other proteins. Luciferase assays of mutant FKBP52 proteins suggest that FKBP52's binding to β-catenin involves the FKBP52 proline-rich loop and may act independently of Hsp90 binding. Interestingly, it appears that this synergistic effect is promoter-specific, suggesting that regulation by these proteins occurs at the transcriptional level. We have successfully abrogated the synergism of these proteins using the FKBP52-specific inhibitor MJC13, a small molecule developed for use in our laboratory. According to surface plasmon resonance studies, this molecule binds the androgen receptor at the BF-3 regulatory surface, the interaction surface for FKBP52 regulation of receptor. According to recent findings, AR, Wnt, and Human Epidermal Growth Factor Receptor 2 signaling pathways are linked in molecular apocrine breast cancer progression. We therefore hypothesize that our findings could be relevant to breast cancer as well as prostate cancer. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-07-02.
Abstract 593: Embelin induces reactive oxygen species-mediated apoptosis in PTC cells.
Authors: Shahab Uddin, Maqbool Ahmed, Azhar R. Hussain, Khawla S. Al-Kuraya
Journal: Cancer Research (2013)

Abstract The X-linked inhibitor of apoptosis (XIAP) is a promising new molecular target for the design of novel anticancer drugs aiming at overcoming apoptosis-resistance of cancer cells to. Recent studies demonstrated that the BIR3 domain of XIAP where caspase-9 and Smac proteins bind is an attractive site for designing small-molecule inhibitors of XIAP. Embelin, identified primarily from the Embelia ribes plant, is one such compound shown to exhibit chemopreventive, anti-inflammatory, and apoptotic activities via inhibiting XIAP activity. In this study we found tthat embelin generated a dose dependent Reactive oxygen species (ROS) in PTC cell lines. Pretreatment of PTC cell with N-acetyl-Lcysteine, an scavenger of ROS prevented embelin mediated inhibition of cell proliferation and apoptosis. Further more, NAC pretreatment also abrogated embeling mediated mitochondrial apoptosis. In addition treatment of PTC cell lines with embelin causes activation of p38, a stress related map kinases leading to up-regulation of death receptor 5 (DR5). Interestingly NAC pretreatment prevented its activation as well as up-regulation of DR5. Altogether, these data suggest a novel function for embelin causes inhibition of cell proliferation and induction of apoptosis via generation of ROS a suppressor of XIAP pathway via generation of ROS in PTC cells, and raise the possibility that this agent may have a future therapeutic role in PTC and possibly other malignancies with up-regulated XIAP pathway. Citation Format: Shahab Uddin, Maqbool Ahmed, Azhar R. Hussain, Khawla S. Al-Kuraya. Embelin induces reactive oxygen species-mediated apoptosis in PTC cells. [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 593. doi:10.1158/1538-7445.AM2013-593
<i>Notes from the Field: Mycobacterium abscessus</i>Infections Among Patients of a Pediatric Dentistry Practice — Georgia, 2015
Authors: Gianna Peralta, Melissa Tobin-D’Angelo, Angie Parham, Laura Edison, Lauren Lorentzson, Carol Smith, Cherie Drenzek
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

On September 13, 2015, the Georgia Department of Public Health (DPH) was notified by hospital A of a cluster of pediatric Mycobacterium abscessus odontogenic infections. Hospital A had provided care for nine children who developed presumptive or confirmed M. abscessus infection after having a pulpotomy at pediatric dentistry practice A (dates of onset: July 23, 2014-September 4, 2015). During a pulpotomy procedure, decay and the diseased pulp are removed to preserve a deciduous tooth. DPH initiated an investigation to identify the outbreak source and recommend prevention and control measures.
Unusual False-Positive Radioiodine Whole-Body Scans in Patients With Differentiated Thyroid Carcinoma
Authors: MASSIMO SALVATORI, IDA SALETNICH, VITTORIA RUFINI, LUIGI TRONCONE
Journal: Clinical Nuclear Medicine (1997)

Radioiodine whole-body imaging is the most accurate method in the diagnosis of metastases from differentiated thyroid cancer. However, false-positive images rarely occur. The authors report unusual cases of thymic hyperplasia and post-traumatic skull changes mimicking mediastinal, skull, or cerebral metastases. Nonthyroidal causes were diagnosed by other radionuclide studies (bone and brain scintigraphy) and CT scans. Follow-up and undetectable thyroglobulin levels helped confirm the benign cause.