tbuckley/cabot-search huggingface dataset:
Abstract 5223: Towards MYC targeted cancer therapy: Noninvasive molecular imaging of c-Myc signaling
Authors: Hua Fan-Minogue, Zhongwei Cao, Paulmurugan Ramasamy, Chan Carmel, Tarik Massound, Felsher Dean, Sanjiv Gambhir
Journal: Cancer Research (2010)

Abstract MYC protein regulates a variety of human genes and is deregulated in most of human cancers. The deregulation of MYC is at multiple levels, from gene transcription to mRNA translation and protein activity. Activation of Myc protein is phosphorylation-mediated and has been found to be essential for development of many cancers. Here, we developed a bioluminescent sensor, using protein assisted split luciferase complementation system, to noninvasively detect the phosphorylation-mediated activation of the cytoplasmic Myc (c-Myc). In this sensor system, the c-Myc phosphorylation motif and the phosphorylation recognition domain of GSK3beta were fused with the two split luciferase fragments respectively. Phosphorylation induced c-Myc interaction with GSK3beta resulted in complementation of the two split luciferases and reconstitution of luciferase activity. Signal of the optimal sensor was specific for the c-Myc phosphorylation. It detected as low as 2-fold higher levels of c-Myc phosphorylation in cancer cells versus normal cells. It also detected the temporal regulation pattern of c-Myc phosphorylation upon serum stimulation in normal cells. MAP kinase inhibitor, PD98059 and U0126, and Atorvastatin (AT), induced dose dependent signal reduction in tumor cells, which was correlated with the decrease of endogenous c-Myc phosphorylation. In mouse tumor xenograft models, the sensor detected the inhibitory effects of AT well before there was a detectable difference in tumor size (P&amp;lt;0.05). For the first time, we developed a sensor that can noninvasively monitor phosphorylation mediated c-Myc activation. It may also facilitate drug development by allowing rapid readout of inhibition effect in high throughput drug screen for MYC-targeted cancer therapy. 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 5223.
286Cardioprotective potential of subcutaneous and visceral adipose-derived stem cells
Authors: C Chi, B Xiang, JX Deng, HY Lin, K Natarajan, F Lin, HY Liu, DH Freed, RC Arora, GH Tian
Journal: Cardiovascular Research (2014)

Background: Adipose-derived stem cells (ASC) from both subcutaneous and visceral adipose tissues have been studied individually and separately. No studies have been performed to directly compare their biological properties and therapeutic function in treatment of congestive heart failure (CHF). This study was therefore designed to comparatively analyze their biological properties and cardiac therapeutic function.
PRELIMINARY EVALUATION OF Tc-99m BnAO, A NON-NITROAROMATIC HYPOXIA AGENT
Authors: Xiu guo Zhang, James R Ballinger, Alfred Pollak, John R Thornback, A M Rauth
Journal: Clinical Nuclear Medicine (1998)

Zhang, Xiu guo; Ballinger, James R; Pollak, Alfred; Thornback, John R; Rauth, A M Author Information
PMO-167 Presence of viable HCV RNA in monocytes at the end of treatment predicts relapse in genotype 3 HCV infection
Authors: M E Cunningham, A Javaid, J A Waters, G R Foster
Journal: Gut (2012)

<h3>Introduction</h3> Although genotype (G)3 HCV is generally regarded as “easy to treat”, based on clinical trial data showing response rates of up to 80%, real world studies have shown substantially lower rates of treatment response (45%), particularly in patients with advanced fibrosis or cirrhosis. Most patients who fail treatment for G3 HCV initially respond to antiviral therapy, but relapse after the end of treatment. HCV RNA has been demonstrated in peripheral blood mononuclear cells from patients with chronic HCV, but whether viral replication occurs in these cells remains controversial. This study tests the hypothesis that viable HCV in monocytes at the end of treatment predicts relapse in patients with G3 HCV. <h3>Methods</h3> CD14 (+) monocytes from patients at the end of treatment for G3 HCV were isolated and fused with HuH7 cells. The fused cells were maintained in tissue culture for up to 5 days, before extraction of HCV RNA and quantification by PCR. p Values were derived using the Mann–Whitney U test for comparison of non-parametric data. Results are expressed as mean ± SEM. <h3>Results</h3> HCV RNA increased up to fivefold in fused compared to unfused monocytes. Viral protein production was demonstrated in fused cells by indirect immunofluorescence, confirming that viral replication occurs in the fused cells. Fused monocytes from patients who relapsed after treatment showed a significantly greater increase in HCV RNA than those from patients with a sustained virological response (246.8±103.9%, compared to 5±33.9%, p=0.02). <h3>Conclusion</h3> These data demonstrate that the presence of replication-competent HCV in monocytes at the end of treatment predicts relapse in patients with G3 HCV. Monocytes may act as a sanctuary site for HCV virions during interferon-based treatment, facilitating relapse after withdrawal of therapy. <h3>Competing interests</h3> M Cunningham: None declared, A Javaid: None declared, J Waters: None declared, G Foster Grant/Research Support from: Roche, Janssen, Tibotec, Novartis, Consultant for: Abbott, BI, BMS, Chughai, Janssen, Merck, Novartis, Roche, Tibotec.
AB0051 Toll-Like Receptor 2 Activation Induces Pro-Inflammatory, Inflammasome and Notch Signalling Pathways in Rheumatoid Arthritis
Authors: T. Mcgarry, W. Gao, M. Connolly, G. Walsh, J. McCormick, D.J. Veale, U. Fearon
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Rheumatoid arthritis (RA) is characterised by inflammation and proliferation of synovial tissue, leading to progressive degradation of articular cartilage and bone. <h3>Objectives</h3> This study examines the effect of Toll-like Receptor (TLR) 2 activation on the inflammasome, cell migration/invasion and Notch signalling pathways. <h3>Methods</h3> RASFC and RA <i>ex vivo</i> explant cytokine release and NLRP3 expression in response to Pam3CSK4 (TLR2-ligand) (1μg/ml) were measured by ELISA, MSD multiplex assay and Western Blotting. TLR2-induced RASFC invasion, migration/cytoskeletal rearrangement, MMP-3 and TIMP-1 expression were assessed by wound repair assays, F-actin immunofluorescence and ELISA. Notch-1 expression in RASFC and whole RA <i>ex vivo</i> explant in response to Pam3CSK4 (1μg/ml) was determined by Western Blotting and RT-PCR. Expression of Notch signaling components (Notch-1, Dll-4, Jagged-1 and HRT-1) were assessed in RA, osteoarthritis (OA) and healthy control synovial tissue by immunohistochemistry. Finally, TLR2-induced cytokine production, cell migration and cytoskeletal rearrangement in the presence or absence of Notch-1 siRNA or a γ-secretase inhibitor N-(N-(3,5-Difluorophenacetyl-L-alanly))-S-phenylglycine-t-Butyl Ester (DAPT) was assessed. <h3>Results</h3> Pam3CSK4 specifically induced IL-6, IL-8, TNFα and IL-1β in RA <i>ex vivo</i> explants and RASFC (p&lt;0.05), with no increase in IFNγ. Pam3CSK4 significantly induced NLRP3 expression and downstream inflammasome-related cytokines IL-1β and IL-18 (p&lt;0.05). Pam3CSK4 significantly induced cell migration, ECM degradation and increased the MMP-3/TIMP-1 ratio (all p&lt;0.05). Pam3CSK4 induced RA synovial explant outgrowth consistent with TLR2-induced RASFC migration and ECM degradation. Notch signalling components were significantly increased in RA synovium compared to OA and control synovium (p&lt;0.05). Pam3CSK4 induced Notch-1 and Jagged-1 mRNA expression with differential effects observed for active Notch-1 intracellular (IC) protein expression. Pam3CSK4-induced cytokine production was in part inhibited in the presence of either Notch-1 siRNA or DAPT. <h3>Conclusions</h3> TLR2 activation in RA activates inflammasome, cytokine production and migrational/invasive mechanisms, effects that may in part be mediated by the Notch-1 signalling pathway. <h3>Disclosure of Interest</h3> T. Mcgarry: None declared, W. Gao: None declared, M. Connolly: None declared, G. Walsh: None declared, J. McCormick: None declared, D. Veale Grant/research support: MSD, Abbvie, MSD, Pfizer, Roche, Consultant for: Pfizer, Roche, Speakers bureau: Abbott, MSD, Pfizer, Roche, U. Fearon: None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5131
MELANOTIC MELANOMA DETECTION WITH I-123 IMP.
Authors: M. B. Cohen, R. E. Saxton, R. R. Lake, L. A. Cagle, L. S. Graham, L. S. Yamada, M. P. Gan, G. T. Bronca, K. L. Greenwell
Journal: Clinical Nuclear Medicine (1987)

Cohen, M. B.; Saxton, R. E.; Lake, R. R.; Cagle, L. A.; Graham, L. S.; Yamada, L. S.; Gan, M. P.; Bronca, G. T.; Greenwell, K. L. Author Information
SAT0149 High EULAR response rate in rheumatoid arthritis patients switching or dose-escalating anti-TNF therapy:
Authors: R.P. Poggenborg, H. Skjødt, R. van Vollenhoven, L. Cöster, O.R. Madsen, M. Østergaard
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Introduction of infliximab and adalimumab has been a major advance in the treatment of rheumatoid arthritis (RA), but some patients initially responding to infliximab 3 mg/kg/8th week are unable to sustain clinical response. <h3>Objectives</h3> To establish whether RA patients with an unsustainable clinical response to infliximab 3 mg/kg/8th week achieves long-term treatment response by dose escalation to infliximab 3 mg/kg/6th-4th week, or by switching to adalimumab 40 mg s.c. eow. <h3>Methods</h3> We included 13 RA patients from Denmark and Sweden with at least 6 month prior treatment with infliximab 3mg/kg/8th, who after an initial clinical response showed moderate to severe disease activity (DAS28 &gt;3.2) and a fading response to infliximab. Fading response was defined as: 1) remission (DAS28 &lt;2.6) while on infliximab, and increased disease activity (DAS28 &gt;3.2); and/or 2) an increase in DAS28 score of 1.2 or more; and/or 3) an increase in HAQ score of 0.5 or more. Patients were randomized to either adalimumab (group 1) or infliximab (group 2A) treatment. Infliximab treated patients who had insufficient response at week 12, could be increased in dose interval to every 4th week (group 2B). <h3>Results</h3> Baseline characteristics (median (range)) for all included patients were: male/female: 3/10, age: 57 (26-78) years, duration of RA: 6 (2-40) years, time treated with infliximab before inclusion: 11 (6-72) month, time since last infusion with infliximab: 52 (40-85) days, patients in randomization group (adalimumab/infliximab): 6/7, 28-TJC: 11 (3-18), 28-SJC: 5 (1-17), HAQ-score: 1.25 (1.0-1.63), and CRP: 17 (4-88) mg/L. Three patients discontinued the trial prematurely (two adalimumab treated patients due to severe pneumonia and lack of efficacy, respectively, and one infliximab treated patient due to lack of efficacy), and they all had a moderate EULAR response at the discontinuation visit. Of 10 patients completing all visits a good EULAR response was achieved by 3 (group 1: 1 patient, group 2A: 2 patients), and good or moderate EULAR response was achieved by 7 patients (group 1: 3 out of 4 patients, group 2A: 3 out of 4 patients, group 2B: 1 out of 2 patients). Table 1 shows DAS28 and ACR response. Median (range) and percentages are shown. Changes did not reach statistical significant levels. <h3>Conclusions</h3> In a randomized study of patients with fading clinical response to infliximab 3mg/kg/8th week moderate or good EULAR response was obtained in the majority (70-80%) of patients by increasing the dose of infliximab or switching to adalimumab. <h3>Disclosure of Interest</h3> None Declared
Abstract 5438: Gene expression profiles resulting from stable and transient loss of p53 mirrors its role in tissue differentiation.
Authors: Oliver Couture, Eric Lombardi, Kendra Davis, Emily Hays, Nalini Chandar
Journal: Cancer Research (2013)

Abstract The tumor repressor gene, p53, is involved in a variety of cellular activities ranging from stress, differentiation and cell cycle regulation. In our previous studies we have shown p53’s transcription activating role to be important in osteoblast differentiation. There is still a debate in the literature as to whether p53 inhibits or promotes differentiation. We have found p53 heterozygous mice to show a p53 dependency on some bone marker gene expression while the same is absent in p53 null mice. This deficiency of p53 has also been shown to produce more osteosarcomas than a complete loss of p53. This suggests that the presence of p53 is able to modify the environment within pre osteoblasts based on its ability to regulate key bone specific genes. In the present study we compared changes in gene expression resulting after either a transient or stable reduction in p53. Accordingly we reduced p53 levels in C2C12 cells capable of both myoblast and osteoblast differentiation transiently, and compared the changes in gene expression of candidate genes to cells with stable p53 knockdown. Using a PCR array to assay p53 target genes, we have found differential expression profiles when comparing stable versus transient knockdown. As expected several of genes that were profoundly affected after transient p53 loss were related to apoptosis and cell cycle regulation. Stable p53 loss produced a greater change in MyoD and other transcription factors with tissue specific roles suggesting that long term effect of p53 loss affects tissue homeostasis to a greater degree than changes resulting from acute loss of p53. These differences in gene expression were also validated by measuring promoter activities of different pathway specific genes involved in differentiation. These studies suggest that an important role for p53 is context dependent, with a stable reduction in p53 expression profoundly affecting normal tissue physiology than its acute loss. Citation Format: Oliver Couture, Eric Lombardi, Kendra Davis, Emily Hays, Nalini Chandar. Gene expression profiles resulting from stable and transient loss of p53 mirrors its role in tissue differentiation. [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 5438. doi:10.1158/1538-7445.AM2013-5438
Abstract 4144: The treatment with a derivative of Vitamin A (ATRA) modulates the expression and subcellular localization of Protein Kinase C (PKC) delta and induces growth inhibition in normal and tumor derived mammary cells
Authors: Damian E. Berardi, María I. Díaz Bessone, Elisa D. Bal de Kier Joffé, Laura B. Todaro, Alejandro J. Urtreger
Journal: Cancer Research (2010)

Abstract Retinoids may exert some of their effects on cell differentiation and malignant phenotype reversion through the interaction with different PKC isoforms. In the present work we addressed the following issues: A)- the role of ATRA on the in vitro growth potential of LM3, a murine mammary tumor-derived cell line; NMuMG, a normal murine mammary cell line and MDA-MB231, a human breast cancer-derived cell line. B)- the effect of retinoid treatment on the expression and subcellular distribution of PKCδ and C)- the importance of PKCδ in the activity of retinoid receptors. ATRA treatment (1μM, 72h) induced a significant growth inhibition in the analyzed murine cell lines. This phenomenon was associated with the reduction of pERK1 levels (80±9% and 40±5% in LM3 and NMuMG cells respectively) and the increase of the cell cycle inhibitor p27 in the nuclear fraction without altering the expression of Cyclin D1 in both murine cell lines. None of these modulations were observed in the ATRA unresponsive MDA-MB241 cell line. By Western blot we could determine that 72h treatment with ATRA induced an increase of PKCδ protein levels both in the nuclear fraction of LM3 cells (4-fold) and in the cytoplasm (2- and 3-fold for LM3 and NMuMG cells respectively). On the contrary, in MDA-MB241 cells PKCδ expression was reduced after ATRA exposure. Interestingly, pharmacological silencing of PKCδ in LM3 cells prevented the activation of retinoid receptors by ATRA, as evidenced by a reporter gene assay (RARE-Luciferase). Our results suggest that, in ATRA-responsive cells, the treatment with this vitamin A derivate inhibits in vitro growth, by reducing mitogenic signaling, by increasing the expression of a cell-cycle inhibitory protein as well as by increasing PKCδ an isoform usually associated with growth inhibition and apoptosis induction. The subcellular localization was also altered by this treatment in LM3 cells. Moreover, the effect of ATRA exerted through the activation of its specific nuclear receptors would depend on the nuclear translocation of this PKC. 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 4144.
Abstract 2208: Overexpression of NDRG1 inhibits cell migration of breast cancer cells via reactive oxygen species during reoxygenation
Authors: Liang-Chuan Lai, Yi-Yu Su, Kuo-Chih Chen, Mong-Hsun Tsai, Yuh-Pyng Sher, Tzu-Pin Lu, Eric Y. Chuang
Journal: Cancer Research (2011)

Abstract One characteristic of tumor microenvironment is oxygen fluctuation, which results from hyper-proliferation and abnormal metabolism of tumor cells as well as disorganized neo-vasculature. Reoxygenation in tumor microenvironment can induce oxidative stress, which further leads to DNA damage and genomic instability. Although multiple cellular responses are activated in order to survive under this microenvironment, little is known about the dynamic response upon reoxygenation. Therefore, in order to investigate the transcriptional response of tumor adaptation to reoxygenation, breast cancer cells MCF-7 was cultured under 0.5% of hypoxia for 24h followed by 24h of reoxygenation in normoxia. Cells were harvested respectively at 0, 1, 4, 8, 12, and 24h during reoxygenation. The genomic profiling of MCF-7 upon reoxygenation was examined using Illumina Human-6 v3 BeadChips. We identified 127 differentially expressed genes in which 53.1% were up-regulated and 46.9% were down-regulated upon reoxygenation. Pathway analysis revealed that HIF-1-alpha transcription factor network was most significantly (P=2.02×10-3) enriched in these differentially expressed genes. Among these genes, a group of selected genes of interest were further validated by quantitative real-time PCR. In particular, NDRG1 was highly suppressed upon reoxygenation. NDRG1 (human N-myc down-regulated gene 1) is associated with a variety of stress and cell growth-regulatory conditions. To characterize whether NDRG1 play a role in reoxygenation, NDRG1 protein was overexpressed in MCF-7 cells. Upon reoxygenation, overexpression of NDRG1 inhibited cell migration, and this inhibition could be reversed by adding reactive oxygen species scavengers. Our results revealed dynamic expression profiling of MCF-7 upon reoxygenation, and demonstrated that NDRG1 is involved in tumor adaptation to reoxygenation. 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 2208. doi:10.1158/1538-7445.AM2011-2208
Abstract 471: A case of bone-metastatic breast cancer resulted in complete remission 5 years after the comprehensive treatment including autologous formalin-fixed tumor vaccine.
Authors: Fumito Kuranishi, Tadao Ohno
Journal: Cancer Research (2013)

Abstract Introduction: All cases, so far we have experienced,of bone-metastatic breast carcinoma patients show the downhill course to a tragic ending despite of intensive chemo-radiation therapy. We here report a case of advanced breast cancer that has been additively treated with autologous formalin-fixed tumorvaccine (AFTV) (Clin Cancer Res 10: 1574-9 2004). Case : A 53 years old female was diagnosed bearing a bone metastasis of breast cancer at vertebra Th7 by bone scintigraphy, MRI and SPECT. The breast was operated, irradiated according to palliative radiation therapy with 36 Gy, vaccinated with AFTV, and then chemotherapy (CEF) was done as the last step of adjuvant therapy. Afterwards aromatase inhibitor and zoledronic acid hydrate was used for maintenance therapy. Five years later, the bonemetastasis has disappeared and she was diagnosed complete remission. Tumor markers have been in normal level . QOL of this patient is good at present. Conclusion: Complete remission of bone metastasis of breast carcinoma is very rare. In this case, the preceded use of AFTV and radiation to the chemotherapy may have contributed to the cure. Additional use of AFTV should be considered in a larger scale clinicaltrial to improve therapeutic efficacy in bone-metastatic breast carcinoma. Citation Format: Fumito Kuranishi, Tadao Ohno. A case of bone-metastatic breast cancer resulted in complete remission 5 years after the comprehensive treatment including autologous formalin-fixed tumor vaccine. [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 471. doi:10.1158/1538-7445.AM2013-471
P801 DO SERUM MARKERS OF CELL INJURY AND DEATH HAVE POTENTIAL TO BECOME MECHANISTIC MARKERS IN NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD)?
Authors: J.I. Grove, D.J. Antoine, P. Kaye, M.H. Miller, J.F. Dillon, M.E. Allison, M.W. James, E.A. Wilkes, A.P. Jackson, I.N. Guha, D.P. Williams, G.P. Aithal
Journal: Journal of Hepatology (2014)
Metastatic Pulmonary Pheochromocytomas: Positive I-123 MIBG SPECT With Negative I-131 MIBG and Equivocal I-123 MIBG Planar Imaging
Authors: SHINSAKU TSUCHIMOCHI, MASAYUKI NAKAJO, YOSHIAKI NAKABEPPU, ATSUSHI TANI
Journal: Clinical Nuclear Medicine (1997)

Pulmonary metastases from malignant pheochromocytoma were seen with I-123 MIBG SPECT in a 16-year-old girl but were not visualized with I-123 MIBG planar imaging. She had a left adrenalectomy for a pheochromocytoma 7 years earlier. Two small pulmonary nodules were seen on chest X-ray and CT scans.
Risk assessment and periodontal prevention in primary care
Authors: Raul I. Garcia, Robert Compton, Thomas Dietrich
Journal: Periodontology 2000 (2016)

Abstract The role of risk factors and risk assessment in the prediction of clinical periodontal outcomes, and thus in patient management, continues to be a subject of high professional interest and clinical relevance globally. Advances in our understanding of periodontal disease causality and the role of risk factors as predictors of future disease risk have led to the development of various quantitative tools to calculate risk and inform clinical decision‐making. We review the conceptual basis for periodontal risk calculation and frame its potential, as well as its limitations, in the context of similar advances in medical care. Lastly, we discuss how broader health‐policy changes are taking place that will probably lead to incorporation of risk‐factor assessments in periodontal treatment planning and care management.