tbuckley/cabot-search huggingface dataset:
Abstract 1644: Microglia promote glioma cell migration and dispersal by activating the PLCγ1 and Pyk2 signaling cascade.
Authors: Kimberleve Rolon-Reyes, Miguel Mendez, David E. Rivera-Aponte, Serguei N. Skatchkov, Misty J. Eaton, Lilia Kucheryavykh
Journal: Cancer Research (2013)

Abstract Glioblastoma multiforme is one of the most aggressive and fatal brain cancers mostly because of the highly invasive nature of glioma cells. The ability of glioma cells to disperse to healthy brain stroma makes surgical and chemotherapeutic treatments mostly ineffective. Microglia infiltrate most gliomas and release factors, which favor tumor growth and dispersal. We hypothesize that microglia residing within the tumor stimulate glioma cell migration and dispersal through the phospholipase C (PLC)γ1 and proline rich tyrosine kinase 2 (Pyk2) signaling cascade. In the present study, we investigated rodent C6 and GL261 as well as human glioma cell lines with varying levels of invasiveness: U-87MG, A172, and HS683. Using a standard invasion assay, we demonstrated that the presence of rodent or immortalized human microglia in the bottom compartment of Boyden chambers activated invasion of all glioma cell types. Knock-down of PLCγ1 and Pyk2 proteins using siRNA reversed the stimulatory effect of microglia on glioma invasion in both cell lines. Pharmacological blockers of PLC (U73872 1nM) and Pyk2/focal adhesion kinase (FAK) (PF562271 20nM) also completely eliminated the ability of microglia to stimulate glioma cell migration in a wound healing assay. Using Western blot, we found upregulation of phosphorylated Tyr579/580 Pyk2 protein in glioma cells treated with microglia conditioned medium. Taken together, these data indicate that microglial cells activate glioma cell migration/dispersal through the pro-migratory Pyk2 and PLCγ1 signaling pathway in glioma cells. This research was made possible by NIH grant numbers: G11 HD052352, G12 RR03035, 8G12MD007583-27, U54 NS039408, UCC Pilot Project Program and Title V PPOHA grant number P031M105050 from the US Dept. of Education. Citation Format: Kimberleve Rolon-Reyes, Miguel Mendez, David E. Rivera-Aponte, Serguei N. Skatchkov, Misty J. Eaton, Lilia Kucheryavykh. Microglia promote glioma cell migration and dispersal by activating the PLCγ1 and Pyk2 signaling cascade. [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 1644. doi:10.1158/1538-7445.AM2013-1644
California Governor Plans Major Cuts in Anti-Tobacco Program
Authors: C. Vanchieri
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article California Governor Plans Major Cuts in Anti-Tobacco Program Get access Cori Vanchieri Cori Vanchieri Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 7, April 1992, Pages 472–473, https://doi.org/10.1093/jnci/84.7.472 Published: 01 April 1992
Biological effects of low-level exposures: a perspective from U.S. EPA scientists.
Authors: J M Davis, W H Farland
Journal: Environmental Health Perspectives (1998)

Biological effects of low-level exposures (BELLE) may be very important in characterizing the potential health risks of environmental pollutants. Before some features of BELLE, such as effects that may be modulated by adaptive or defense mechanisms, can be taken into greater consideration in U.S. Environmental Protection Agency risk assessments, however adequate information on a toxicant's mode of action and answers to other questions are needed.
Advantages of Diffusion Weighted Imaging of Pulmonary Nodules and Masses: Comparison with Positron Emission Tomography
Authors: K. Usuda, M. Sagawa, N. Motono, M. Ueno, M. Tanaka, Y. Machida, S. Maeda, M. Matoba, H. Tonami, Y. Ueda
Journal: Annals of Oncology (2015)
Abstract 2007: Concurrent gene promoter hypermethylation and allele loss occurs infrequently in head and neck squamous cell carcinomas
Authors: Graham M. Poage, Brock C. Christensen, E. Andres Houseman, Michael D. McClean, John K. Wiencke, Marshall R. Posner, John R. Clark, Heather H. Nelson, Carmen J. Marsit, Karl T. Kelsey
Journal: Cancer Research (2010)

Abstract Malignancies arise as a result of environmental insults that cause an accumulation of molecular changes in the genomes and epigenomes of the affected somatic cells. Numerous models have been described that outline the set of consequential alterations for different tumor types throughout carcinogenesis. The implication of Knudson's two-hit hypothesis for inactivation of tumor suppressor genes, with regards to the emerging field of integrative genomics, is that this gene silencing can be achieved through deletion of one allele and hypermethylation of the other. We aimed to characterize this process in the upper airway epithelium through an array-based molecular investigation of 19 head and neck squamous cell carcinomas (HNSCCs). We utilized a genome-wide integrated approach, combining data from DNA methylation arrays (&amp;gt;1400 loci) with SNP-based resequencing (&amp;gt;500K loci) copy number data, and a novel analytical approach involving model-based clustering methods. We found that while methylation and gene copy number were well-correlated for a number of loci, few tumor suppressors exhibited concomitant silencing alterations. In fact, of the commonly altered genes in this disease only CDKN2A possessed both hypermethylation and allele loss, and only at one locus for a minority of tumors (3/18). Three tumors also lacked one copy of the maintenance methyltransferase gene, DNMT1, and these samples had a lower average methylation across all loci measured than those with a normal copy number (P&amp;lt;0.0001) at this site. Our results suggest that coordination of molecular mechanisms rarely occurs at single genes; however they may be linked through global regulatory processes affecting the patterns of coordinated alterations in order to control carcinogenic gene pathways. A thorough understanding of these alteration patterns and integration of such molecular processes are critical for the identification of cellular targets/biomarkers in HNSCC and for rational therapeutic administration. 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 2007.
Abstract 923: Separating the wheat from the chaff: A first look at the Cancer Cell Lines Encyclopedia sequencing data
Authors: Gregory V. Kryukov, Michael F. Berger, Nicolas Stransky, Jordi Barretina, Robert Onofrio, Giordano Caponigro, Carrie Sougnez, John Monahan, Erica Shefler, Kavitha Venkhatesan, Kristian Cibulskis, Paula Morais, Andrey Sivachenko, Jodi Meltzer, Michael Lawrence, Alex Ramos, Gad Getz, Broad's Genome Sequencing Platform, Joseph Thibault, Scott Mahan, Michael Jones, Michael Morrissey, Dmitry Sonkin, Kristin G. Ardlie, Todd Golub, Barbara Weber, Markus Warmuth, William Sellers, Jennifer Harris, Robert Schlegel, Levi A. Garraway
Journal: Cancer Research (2011)

Abstract Comprehensive characterization of cancer genomic alterations and understanding their functional roles are important steps in the development of personalized cancer treatments. The Cancer Cell Lines Encyclopedia project aims to relate genomic alterations to drug sensitivity of cancer cells. Cancer cell lines are indispensable resource for researchers because of their convenience for high-throughput profiling and availability for follow-up experiments. We sequenced the coding regions of 1645 genes in over 800 cancer cell lines representing 32 different tumor types. Genes were selected on their likelihood to be cancer-related and sequenced using next-generation Illumina technology after hybrid selection of exonic regions. Although, the absence of matched normal cell lines precludes direct distinction of somatic from germline mutations, we were able to select a subset of mutations highly enriched in somatic events combining the following three approaches: subtraction of known polymorphisms, prediction of strongly detrimental mutations (including computational predictions of amino acid substitutions’ effects on protein function) and detection of abnormal linkage disequilibrium patterns for recurring mutations. We then searched for the three independent indicators of the potential involvement of mutated genes in cancer: the presence of an unusually high fraction of strongly damaging mutations within a gene, statistically significant deviation of distribution of mutations between cancer types from random expectation and clustering of mutations within a gene. Combined analysis of these lines of evidence revealed both known and novel potential tumor suppressors and oncogenes. These data should become an import resource for cancer researchers in their search for personalized cancer 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 923. doi:10.1158/1538-7445.AM2011-923
CAPSULE-BASED C-14 UREA BREATH TEST FOR HELICOBACTER PYLORI: EARLY EXPERIENCE AND COMPARISON WITHLIQUID-BASED TEST
Authors: H. R. Balon, E. Roff, H. J. Dworkin
Journal: Clinical Nuclear Medicine (1997)

Scientific Abstracts Central Chapter, Society Of Nuclear Medicine Meeting, April 11-13, 1997, Grand Geneva Resort, Lake Geneva, Wi
Abstract 491: Defining the origins of ras/p53 mediated squamous cell carcinoma
Authors: Andrew C. White, Kathy Tran, Joan Khuu, Bill Lowry
Journal: Cancer Research (2011)

Abstract The precise identity of cancer cells of origin and the molecular events of tumor initiation in epidermal squamous cell carcinoma (SCC) are unknown. Here we show that malignancy potential is related to the developmental capacity of the initiating cancer cell in a genetically defined, intact, and inducible in vivo model. Specifically, these data demonstrate that hair follicle stem cells (SCs) serve as cancer cells of origin when oncogenic Kras is expressed and p53 is ablated, whereas their more developmentally restricted progeny, the transit amplifying (TA) cells, are unable to generate even benign tumors in the same genetic context. Employing a temporal model of tumorigenesis in situ, we highlight the phenotypes of cancer progression from hair follicle SCs including hyperplasia, dysplasia, epithelial to mesenchymal transition, and SCC formation. Furthermore, we provide insights into the inability of hair follicle TA cells to respond to tumorigenic stimuli. 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 491. doi:10.1158/1538-7445.AM2011-491
P16.26 * MINIMUM APPARENT DIFFUSION COEFFICIENT MEASUREDBY 3T MR IMAGES IN GLIOBLASTOMA AND O6-METHYLGUANINE-DNA-METHYTRANSFERASE GENE PROMOTER METHYLATED STATUS
Authors: F. Asteggiano, A. Vella, E. Scola, E. Pirola, M. Minichiello, M. Miozzo, M. Caroli, L. Bergamasco, P. Rampini, F. Triulzi
Journal: Neuro-Oncology (2014)

INTRODUCTION: Glioblastoma (GBM) is the most aggressive type of primary brain tumour. O6-methylguanine-DNA-methytransferase (MGMT) gene promoter methylation status has proven to be a predictive prognostic marker for longer survival in patients with newly diagnosed GBM treated with surgery, radiotherapy and chemotherapy. Patients showing a methylation of the MGMT promoter have a longer overall survival. We used Diffusion-Weighted Magnetic Resonance Imaging (DW-MRI) to obtain data about brain tumor structure. It is know that an increased perilesional swelling and tumor cellularity affect DW MRI and the Apparent Diffusion Coefficient (ADC). So far, few studies have analyzed the association between ADC values and MGMT methylation status with conflicting results. More trials are needed to assess the predictive value of DWI MRI as a non-invasive assessment of MGMT promoter methylation status that could add helpful information for clinical management. OBJECTIVE: To assess the correlation between ADC values and MGMT promoter methylation status in patients with GBM. MATERIAL AND METHODS: A retrospective analysis of 3 Tesla MR preoperative studies was perfomed in 13 patients with newly diagnosed GBM (7 M,6 F, mean age 60 years). The analysis of ADC value within the tumor was conducted using automatic co-registration between ADC maps and T1 contrast enhanced weighed images, with MathLab®-based SPM8® dedicated software, and semiautomatic quantitative analysis with 3D Slicer®. MGMT status was evaluated with polymerase chain reaction (PCR) real time (Pyromark Q96 ID System®) in the tumor tissue. RESULTS: The relationship between minimum ADC and percentage of MGMT methylation status was tested with Pearson's linear correlation coefficient, showing moderate correlation (r = 0,48). Observing the high variability of the minimum ADC data, the population has been divided into 4 classes, to reduce this problem. Plotted data revealed a strong correlation between minimum ADC plotted groups and MGMT(r = 0,94). Furthermore, minimum ADC values in tumors presenting under the threshold of 20% of MGMT methylation status were significantly different compared to minimum ACD values measured in tumors over 20% of MGMT methylation status (non parametric Mann-Whitney test, p = 0,04). DISCUSSION: DW-MRI may provide important insight into subtypes of GBM with different gene expressions. Recent studies found an association between the ADC values and the MGMT promoter methylation status. Our findings, even if limited by a relatively small population, showed that minimum ADC value measured within tumor was statistically different between GBM showing MGMT status methylation respectively below and above 20%. CONCLUSION: ADC values may be considered as a noninvasive biomarker of GBM MGMT promoter methylation status and furthermore as an index of patients prognosis.
SAT0063 Functional analysis of the primary cilium in rheumatoid arthritis synovial fibroblasts
Authors: K. Klein, B. Michel, R.E. Gay, S. Gay, C. Ospelt
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The primary cilium is a microtubule-based, polarized, antenna structure that emanates from the cell surface of most mammalian cell types. It serves as a sensor that mediates reactions to mechanical and chemical signals from the environment and is therefore, a crucial factor in the communication with neighbouring cells and the environment. <h3>Objectives</h3> To investigate the functional role of the primary cilium expressed on synovial fibroblasts (SF) in the pathogenesis of rheumatoid arthritis (RA). <h3>Methods</h3> The expression of the primary cilium was verified in serum- starved RASF by immunofluorescence microscopy using acetylated tubulin as a marker. Ciliogenesis of RASF was disrupted by transfection of siRNA targeting the ciliary component kinesin family member 3a (KIF3a) before stimulation with TNF-α (10ng/ml) and IL-1β (1ng/ml). Knockdown of KIF3a was verified by Western blotting. Migration and adhesion properties of transfected RASF were analysed by scratch assay (n=2) and a fibronectin-based adhesion assay (n=7), respectively. Expression levels of integrin beta 1 (ITGB1), integrin beta 3 (ITGB3), and integrin alpha V (ITGAV) were measured by SYBR green Real-time PCR and compared to expression levels of RASF that were transfected with scrambled siRNA (n=6). <h3>Results</h3> The primary cilium was detected on the surface of RASF. Migration of RASF with blocked formation of the primary cilium by transfection with siRNA targeting KIF3a was reduced compared to RASF transfected with scrambled siRNA. RASF adhesion to fibronectin was induced by TNF-α (2.1 fold ±0.9, n.s.) and IL-1β (2.3 fold ±1.3, p&lt;0.05), and was reduced in KIF3a siRNA transfected RASF (TNF-α: 1.2 fold ±0.7, p&lt;0.05; IL-1β: 1.3 fold ±0.7, p=0.1142). While IL-1β significantly induced mRNA expression of ITGB1 (1.7 fold ±0.3, p&lt;0.001), ITGB3 (1.8 fold ±0.6, p&lt;0.01) and ITGAV (1.7 fold ±0.7, p&lt;0.01) in control transfected RASF, it had no effect on KIF3a siRNA transfected RASF in which the levels of the analysed integrins after IL-1β stimulation were significantly lower compared to control transfected RASF (ITGB1: 0.9 fold ±0.2, p&lt;0.001; ITGB3: 1.1 fold ±0.3, p&lt;0.001; ITGAV: 1.1 fold ±0.1, p&lt;0.01). <h3>Conclusions</h3> Our data show a functional role of the primary cilium in the migratory and adhesive properties of RASF. Since disruption of ciliogenesis in RASF altered their response to stimulation with TNF-α and IL-1β, we hypothesise that the primary cilium also plays a key role in the transmission of pro-inflammatory signals in RASF. <h3>Acknowledgements</h3> IAR Epalinges, FP7 Masterswitch, IMI-BT Cure, EMDO-Stiftung <h3>Disclosure of Interest</h3> None Declared
Intrathecal Baclofen for the Treatment of Dystonia in Patients with Reflex Sympathetic Dystrophy
Authors: Bob J. van Hilten, Willem-Johan T. van de Beek, Jorrit I. Hoff, Johan H.C. Voormolen, Elmer M. Delhaas
Journal: New England Journal of Medicine (2000)

Patients with reflex sympathetic dystrophy (also known as the complex regional pain syndrome) may have dystonia, which is often unresponsive to treatment. Some forms of dystonia respond to the intrathecal administration of baclofen, a specific gamma-aminobutyric acid-receptor (type B) agonist that inhibits sensory input to the neurons of the spinal cord. We evaluated this treatment in seven women who had reflex sympathetic dystrophy with multifocal or generalized tonic dystonia. First, we performed a double-blind, randomized, controlled crossover trial of bolus intrathecal injections of 25, 50, and 75 microg of baclofen and placebo. Changes in the severity of dystonia were assessed by the woman and by an investigator after each injection. In the second phase of the study, six of the women received a subcutaneous pump for continuous intrathecal administration of baclofen and were followed for 0.5 to 3 years.In six women, bolus injections of 50 and 75 microg of baclofen resulted in complete or partial resolution of focal dystonia of the hands but little improvement in dystonia of the legs. During continuous therapy, three women regained normal hand function, and two of these three women regained the ability to walk (one only indoors). In one woman who received continuous therapy, the pain and violent jerks disappeared and the dystonic posturing of the arm decreased. In two women the spasms or restlessness of the legs decreased, without any change in the dystonia.In some patients, the dystonia associated with reflex sympathetic dystrophy responds markedly to intrathecal baclofen.
Topoisomerase II Inhibition and Cytotoxicity of the Anthrapyrazoles DuP 937 and DuP 941 (Losoxantrone) in the National Cancer Institute Preclinical Antitumor Drug Discovery Screen
Authors: F. Leteurtre, G. Kohlhagen, K. D. Paull, Y. Pommier
Journal: JNCI Journal of the National Cancer Institute (1994)

The cumulative cardiotoxicity of anthracyclines is thought to result from the generation of free radicals. New DNA topoisomerase II inhibitors less prone to redox reactions, such as mitoxantrone and more recently the anthrapyrazoles, were developed to circumvent this toxicity.Two anthrapyrazoles currently in clinical evaluation, DuP 941 (Losoxantrone) and DuP 937, were compared to other topoisomerase II inhibitors with respect to their cytotoxic potency and selectivity and with respect to topoisomerase II inhibition.Cytotoxicity was tested in the 60 cell lines of the National Cancer Institute preclinical antitumor drug discovery screen (NCI screen). The potency of anthrapyrazoles to inhibit purified topoisomerase II was determined. The specificity of drug-induced topoisomerase II pattern of cleavage, one of the cellular determinants of cytotoxicity, was investigated in human c-myc DNA.Using the COMPARE analysis, we found that the most closely related cytotoxic profiles in the NCI screen were between the anthrapyrazoles and mitoxantrone. Among topoisomerase II inhibitors, the cytostatic potency was by decreasing order: mitoxantrone; doxorubicin, which was slightly greater than DuP 941, azatoxin; DuP 937; and amsacrine, which was much greater than VP-16. The potency of mitoxantrone and anthrapyrazoles to generate DNA double-strand breaks, by induction of the topoisomerase II cleavable complexes in nuclear extracts, was in agreement with cytotoxicity. Sequencing of drug-induced topoisomerase II cleavages in c-myc DNA showed a common cleavage pattern for anthrapyrazoles and mitoxantrone. This pattern was different from the patterns obtained with other topoisomerase II inhibitors.At the molecular and cellular levels, anthrapyrazoles are potent topoisomerase II inhibitors closely related to mitoxantrone.These results validate the COMPARE analysis using the NCI screen to predict molecular mechanisms of drug action. Anthrapyrazoles, which are unlikely to produce free radicals, might be useful in the same indications as mitoxantrone, especially for patients with cardiac risks, for pediatric patients, and for patients treated with intensified protocols.
AB0461 Effect of Methotrexate and Glucocorticoids Therapy on Cardiovascular Disease in Patients with Rheumatoid Arthritis
Authors: H. Gerasimova, T. Popkova, D. Novikova, D. Shulgin, D. Olisaeva, E. Nasonov
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> The risk of cardiovascular disease (CVD) is increased in patients (pts) with rheumatoid arthritis (RA). Systemic inflammation and therapy influence the risk of CVD. Immunosuppressive medications may demonstrate both positive and negative effect on the risk CVD in RA pts. <h3>Objectives</h3> To determine the effect of MTX monotherapy, combination MTX with glucocorticiods (GCs) and GCs monotherapy on the frequency of risk factors, subclinical and clinical manifestations of CVD and their complications in RA pts. <h3>Methods</h3> We included 136 pts with RA: 86% - female, 14% - male; the median age was 49 [35;56] years; the duration of disease 96 [27;204] months; DAS28 4,6 [3;6,3]. Fifty-three (39%) pts received methotrexate (MTX), 45 (33%) - combination MTX with GCs (MTX+GC), 38 (28%) - oral GCs monotherapy (GC). There were no differences between age, disease duration, DAS 28 in pts treated with various drugs. Traditional risk factors, carotid atherosclerosis and CVD frequency (myocardial infarction, stroke, angina pectoris) were evaluated. Logistic regression model was assessed to determine the risk of CVD in RA pts. <h3>Results</h3> Dyslipidemia was detected significantly less in RA pts treated with MTX (25/53 (47%)) as compared to pts with GC monotherapy (25/38 (65%), p=0,049). Concentrations of HDL cholesterol in the serum of pts treated with MTX (1,8 [0,9; 2,0]mmol/l) was higher, than pts with MTX+GC (1,3 [1,1; 1,5]mmol/l, p=0,03) and pts with GC (1,2 [1,0; 1,6]mmol/l, p=0,047). There were no differences in concentrations of other lipids. Incidence of other traditional risk factors like smoking, family history of CVD, hypertension, obesity, metabolic syndrome, diabetes mellitus was the same in different groups of pts. Carotid artery atherosclerotic plaques were detected in 15%,19% and 16%, thickening of the intima-media thickness - in 45%, 53% and 56% of pts treated MTX, MTX+GC,GC, respectively. We found myocardial infarction in 1,6%, 4% and 4,8% cases; stroke - 3,9%, 4%, 4,6%; angina pectoris - 10%, 14%, 13% of pts treated MT, MT+GC, GC, respectively. Combination MTX+GC and GC monotherapy showed an increase in risk of cardiovascular events as opposed to MTX monotherapy (OR 1,3; 95% CI 1,1-1,9; OR 1,9; 95% CI 1,2-2,5, respectively). <h3>Conclusions</h3> MTX monotherapy demonstrated advantage in risk of CVD unlike MTX combination with GC and GC monotherapy. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4374