tbuckley/cabot-search huggingface dataset:
Abstract 4940: Activated signaling mechanism of glioblastoma recurrence derived from genetics, epigenetics, and genomics abnormalities
Authors: Guangxu Jin, Junfeng Gao, Stephen T.C. Wong
Journal: Cancer Research (2012)

Abstract Recurrence or progession happens to certain glioblastoma (GBM) patients after given surgeries and complex treatment regimens. This implies that the pathways related to cell growth or apoptosis resistance have been activated. However, it lacks an efficient model to identify the activated pathways from a variety of data generated by the platforms on genetics, epigenetics, and genomics. Here, we develop a new computational model, called as CSB-MOO (Cancer Signaling Bridges - Multiple Objective Optimization), to address signaling mechanism associated with the recurrence or progression of GBM. We used a pathway-driven method to address the activated pathways. In the model of CSB-MOO, a new type of network elements, Cancer Signaling Bridge (CSB), was used to expand the known signaling pathways to the cancer genes (with genetic disorders) of GBM. Facilitated by CSBs, more than 60 known signaling pathways are found to be connected with the cancer genes for GBM. Then, a well-established mathematical method, Multi-Objective Optimization (MOO), was applied to identify activated pathways from multiple-type data. We used Pareto optimal to solve this MOO problem. We applied the CSB-MOO to the multiple-type data of GBM in TCGA (n=595). 15 proteins are activated in the 7 common pathways for both of the patients with and without recurrence/progression. These proteins include EGFR and JAK proteins. The patients without recurrence or progression activate another 11 activated proteins related to metabolic of amino acids (Tryptophan and Phenylalanine). Specifically, the patients with recurrence or progression activate another seventeen proteins, e.g., PIK3R1, and 2 protein complexes, i.e., [PLCG2/PLCG1] and [ITPR3/ITPR2/ITPR1], in which the SH2 domain of PIK3R1 acts an adaptor between the kinases [PLCG2/PLCG1] and the targeted proteins. In addition, these proteins facilitate the signal transduction from EGFR to downstream proteins through mediating phosphorylation. This is consistent with the fact that the recurrence/progression patients can activate the progession of GMB. The identified activated pathways classify the GBM patients with and without recurrence/progression in an accuracy of 80.89% (P &amp;lt; 10−4, Fisher exact test). Survival analysis indicates that the activated pathways with genetics, epigenetics, and genomics patterns accurately predict the patients’ lifespan (P = 0.0007, Chi-squared test). Acknowledgements: This work was supported by NIH grant U54CA149196 to STCW. 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 4940. doi:1538-7445.AM2012-4940
Bone Metastases in a Patient with Colon Cancer Depicted by Tc-99m Carcinoembryonic Antigen Scintigraphy
Authors: V Bongers, M J Verhaar-Langereis, M G Hobbelink, B A Zonnenberg, J M de Klerk
Journal: Clinical Nuclear Medicine (2000)

Because adjuvant chemotherapy and radiotherapy may prolong patient survival, reduce the incidence of metastases, and relieve symptoms in patients with colorectal cancer, accurate staging is critical. The incidence of bone metastases is low and does not justify a routine metastatic bone survey. Furthermore, bone involvement in the absence of liver or lung metastases from colorectal cancer occurs in a minority of cases. Therefore, the use of radioimmunoscintigraphy may be valuable compared with Tc-99m HDP bone scintigraphy. This report shows that Tc-99m carcinoembryonic antigen (CEA) scintigraphy could add clinically significant information when the extent of the colonic cancer is assessed, not only in the locoregional field but also in distant metastases, including the bones.
AB0587 Safety and efficacy of abatacept(ABA) demonstrated in patients with rheumatoid arthritis(RA); 4-year data from phase III open-label, multicenter, long-term extension trial
Authors: Y. Tanaka, T. Abe, T. Takeuchi, A. Yamamoto, N. Miyasaka
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The long-term evidence of ABA for RA patients is limited. <h3>Objectives</h3> To assess the long-term safety and efficacy of ABA in patients with RA. <h3>Methods</h3> This study consisted of 3 cohorts; Phase I (P1, n=13) and P2 (n=178), ABA10mg/kg + MTX or ABA10mg/kg for 192 wks; new patients (N, n=26), intolerant to MTX due to safety reasons (N). All adverse events and efficacy results were recorded. <h3>Results</h3> The average exposure and mean disease duration of 217 patients enrolled in this study was 2.86 and 9.1±7.1 (years), respectively. In total 74.2% patients completed 192 wks period. There was no specific adverse event increased with ABA. The most common AE was nasopharyngitis 56.7%, 46.6 per year of patients. One patient (0.5%) died because of pancreatic carcinoma (causal relationship to study drug:possible). ACR20, DAS28-CRP&lt;2.6, SDAI remission (≤3.3) and Low disease activity (LDA) (≤11) achieved patients ratio increased and maintained steadily and 80.2, 44.7, 12.9 and 52.1% were scored at wks 192, respectively, (Last Observation Carried Forward: LOCF) by the treatment with ABA. <h3>Conclusions</h3> During this study, ABA was well tolerated and its efficacy sustained throughout 192 weeks. <h3>Disclosure of Interest</h3> None Declared
AB1201 Diversity in clinical manifestations of autoinflammatory syndromes in a french paediatric rheumatology referral center
Authors: S. Boiu, B. Neven, S. Compeyrot-Lacassagne, R. Mouy, C. Wouters, M. Gattorno, P. Quartier
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The autoinflammatory syndromes (AISs) include monogenic and polygenic disorders characterized by primary dysfunction of the innate immune system. <h3>Objectives</h3> To describe the clinical spectrum, genetic background and therapy in a cohort of AIS patients followed in a reference Pediatric Rheumatology center. <h3>Methods</h3> Medical records of AIS patients followed until November 2010 and entered in the Eurofever Registry were studied. <h3>Results</h3> Fifty six patients were included: 17 CAPS, 4 TRAPS, 5 HIDS, 18 FMF, 6 CRMO, 2 SAPHO and 4 Behçet's Disease (BD). The median follow-up was 2 years (0-14 years). The male/female ratio was 20/36. The median age was 2.5 years at disease onset and 4 years at diagnosis. Family history was positive in 34% of patients. Clinical manifestations included fever (79%), musculoskeletal (77%), gastrointestinal (63%), mucocutaneous (61%), neurological (41%), ocular (34%), cardiorespiratory (13%), and genitourinary (2%) findings, lymphadenopathy with/or hepatosplenomegaly (16%) and growth impairment (25%). The main organ system manifestations were arthralgia (70%), abdominal pain (50%), urticarial rash (34%), headache (34%), conjunctivitis (16%), generalized lymph node enlargement (13%), and chest pain (9%). Complications/sequelae developed in 45% of patients and involved the musculoskeletal (25%), neurological (21%), gastrointestinal (11%) and ocular (7%) systems. Six patients presented with severe/unusual manifestations: neonatal peritonitis (1 CAPS), pancreatitis (1 TRAPS), acute glomerulonephritis (1 FMF), complicated Henoch-Schonlein purpura (1 FMF), peritoneal adhesions with intestinal occlusion (1 FMF), periorbital pain (1 CRMO) and cerebral thrombosis (1 BD). AISs were associated with other diseases in 2 patients (FMF/Hénoch-Schönlein purpura and CRMO/enthesitis-related arthritis). One mutant allele was found in 16/17 CAPS, 4/4 TRAPS and 4/18 FMF patients. Two mutant allelles were present in 5/5 HIDS and 11/18 FMF patients.The most used therapeutic agents were biologics (54%) (anakinra, canakinumab, etanercept, adalimumab), NSAIDs (48%), colchicine (45%) and corticosteroids (29%). Anti-interleukin-1 therapy and colchicine proved efficacy in CAPS and FMF patients, respectively. In addition, favorable responses demonstrated anti-interleukin-1 therapy in TRAPS, HIDS and colchicine-resistant FMF patients, as well as etanercept in TRAPS, HIDS and CRMO patients non-responsive to NSAIDs. Fifty seven% and 41% of patients were in complete and partial remission, respectively, at last visit. <h3>Conclusions</h3> AISs in children are associated with a broad spectrum of manifestations. A detailed history, thorough review of clinical manifestations and molecular testing of specific causative genes can provide early and accurate diagnosis and institution of efficient therapy. <h3>Disclosure of Interest</h3> None Declared
Estimating the Frequency of Horizontal Gene Transfer Using Phylogenetic Models of Gene Gain and Loss
Authors: Seyed Alireza Zamani-Dahaj, Mohamed Okasha, Jakub Kosakowski, Paul G. Higgs
Journal: Molecular Biology and Evolution (2016)

We analyze patterns of gene presence and absence in a maximum likelihood framework with rate parameters for gene gain and loss. Standard methods allow independent gains and losses in different parts of a tree. While losses of the same gene are likely to be frequent, multiple gains need to be considered carefully. A gene gain could occur by horizontal transfer or by origin of a gene within the lineage being studied. If a gene is gained more than once, then at least one of these gains must be a horizontal transfer. A key parameter is the ratio of gain to loss rates, a/v. We consider the limiting case known as the infinitely many genes model, where a/v tends to zero and a gene cannot be gained more than once. The infinitely many genes model is used as a null model in comparison to models that allow multiple gains. Using genome data from cyanobacteria and archaea, it is found that the likelihood is significantly improved by allowing for multiple gains, but the average a/v is very small. The fraction of genes whose presence/absence pattern is best explained by multiple gains is only 15% in the cyanobacteria and 20% and 39% in two data sets of archaea. The distribution of rates of gene loss is very broad, which explains why many genes follow a treelike pattern of vertical inheritance, despite the presence of a significant minority of genes that undergo horizontal transfer.
CBIO-12EFFECT OF SONODYNAMIC THERAPY WITH 5-AMINOLEVULINIC ACID ON MALIGNANT GLIOMA
Authors: Tadashi Higuchi, Fumio Yamaguchi, Takayuki Asakura, Donghui Ju, Koji Adachi, Takayuki Kitamura, Akio Morita
Journal: Neuro-Oncology (2015)

INTRODUCTION: Photodiagnosis (PD) with 5-aminolevulinic acid (5-ALA) is useful to detect malignant glioma tissue during surgery. On the other hand, photodynamic therapy (PDT) with 5-ALA is not yet popular for malignant gliomas, although PDT is widely used for skin or gastrointestinal cancers. One of the problems of PDT for gliomas is the limit of penetrating distance of light. Since glioma grows invasively into deep tissue, its effect does not reach the peripheral of the tumor. Ultrasound instead can conduct its energy into the deep tissue with less attenuation and is known to activate photosensitizing drug like light. We have been investigating its application for glioma treatment and report the different effects on two glioma cell lines. MATERIALS AND METHODS: Two human malignant glioma cell lines (U-87 MG, SNB-19) were cultured in exponential growth phase. The glioma cells were treated with 5-aminolevulimic acid (5-ALA) for 4 hours and then enclosed in plastic tubes. Ultrasonic device UST-770 (ITO Co., Ltd.) was used for all experiments. Ultrasonication (US) was performed at the condition of 2.0W/cm2, 1.0MHz, 5min and the depth of 3 cm. As control, 5-ALA (-) or US(-) groups were set. The number of cells was counted immediately after SDT and after 48 hour-incubation. RESULTS: The SDT with 5-ALA showed suppressive effect (approximately 15% by comparison with a control data) on U-87 MG. Whereas no effect was seen in other groups of U-87 MG, and all groups of SNB-19. CONCLUSION: SDT with 5-ALA has the potential as an option for treatment of malignant glioma. The conditions have to be investigated for its stable effectiveness. The mechanism of action should also be elucidated to understand the differential effects on each cell lines.
Abstract LB-76: A study of neoadjuvant bevacizumab with standard chemoradiation versus chemoradiation alone in locally advanced rectal cancer
Authors: Christopher G. Willett, Dan G. Duda, Marek Ancukiewicz, Mira Shah, Brian Czito, Rex Bentley, Martin Poleski, Hiroshi Fujita, Gregory Y. Lauwers, Madeline Carroll, Douglas Tyler, Christopher Mantyh, Paul Shellito, Daniel C. Chung, Jeffrey W. Clark, Rakesh K. Jain
Journal: Cancer Research (2010)

Abstract The anti-vascular endothelial growth factor (VEGF) antibody bevacizumab is increasingly being tested with pre-operative (neoadjuvant) regimens in patients with localized cancer, but its effects on metastasis and survival remain unknown. This study examined the outcome of clinical stage II/III rectal cancer patients treated on a prospective phase II study of bevacizumab based chemoradiation and surgery to a contemporarily treated group of patients with standard chemoradiation and surgery at the same institution (Duke University Medical Center). Outcome analyses were performed on: 1. thirty-two patients treated prospectively from 2002 to 2008 with neoadjuvant bevacizumab, 5-fluorouracil and radiation therapy and surgery; versus 2. forty-two patients treated from 2004 to 2008 with capecitabine, radiation therapy and surgery. The current median follow-up is 3 years. While local control was 100% in both groups (i.e., there was no local recurrence), the patients treated with bevacizumab-based chemoradiation and surgery showed statistically significantly higher overall survival rates and a trend higher disease-free survival rates than patients treated with chemoradiation alone and surgery. No statistically significant differences were observed in local control or toxicity between the two groups. These data indicate that adding bevacizumab to neoadjuvant chemoradiation compares favorably to chemoradiation alone in a contemporary population of rectal cancer patients. The efficacy of neoadjuvant bevacizumab will have to be established prospectively in randomized studies, but bevacizumab with standard chemoradiation and surgery shows promising safety profiles and does not appear to increase metastasis after three years in locally advanced rectal cancer patients. This study was partially supported by NIH grants R21-CA99237, P01-CA80124, R01-CA115767, R01-CA85140, R01-CA126642 and Federal Share/NCI Proton Beam Program Income grants, and by the National Foundation for Cancer Research. 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 LB-76.
AB1127 Equivalence of disease activity tools for juvenile idiopathic arthritis
Authors: R.C. Capela, C. Saad-Magalhaes
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Disease activity has been assessed by different tools in Rheumatoid Arthritis (RA) by Disease Activity Score – DAS 28 and Juvenile Idiopathic Arthritis (JIA) by Juvenile Arthritis Disease Activity Score – JADAS, the last scoring 71, 27 and 10 joints respectively. Reduced joint count was proposed for both tools based on compromising comprehensiveness and feasibility and by selecting most frequently affected joints. DAS 28 omits lower extremity joints. <h3>Objectives</h3> Explore equivalence of DAS28 and JADAS in children and adolescents with JIA. <h3>Methods</h3> 178 observations at regular intervals in 8 subjects enrolled in a placebo-controlled clinical trial were examined retrospectively for scoring disease activity with standardized joint count (28, 71, 27, 10), physician global assessment by visual analog scale (VAS 0-10), global assessment by patients/parents (VAS 0-10) and erythrocyte sedimentation rate (ESR) normalized to 0-100 scale. DAS-28 was calculated by formula. JADAS was obtained by direct sum of each component. Paired observations of DAS 28 and JADAS 71, 27 and 10, respectively were analysed by linear regression after conversion to logarithmic scale. <h3>Results</h3> Linear regression for adjustment of DAS and JADAS indicated partial overlap. Along a mean follow up of 18 months a consistent overlap of JADAS 71, 27 and 10 was observed. Although direct score comparison of DAS28 and JADAS cannot be performed, a formula to transform both was obtained: DAS 28 = 1.263 × Log <sub>n</sub> (JADAS 71) – 1.267 (r<sup>2</sup>=0.81); DAS 28 = 1.288 × Log<sub>n</sub> (JADAS 27) – 1.297 (r<sup>2</sup>=0.80) e DAS 28 = 1.285 × Log<sub>n</sub> (JADAS 10) – 1.281 (r<sup>2</sup>=0.76). <h3>Conclusions</h3> Partial overlap and scoring conversion may provide alternative use for adolescents and young adults with either RA or JIA. <h3>References</h3> Consolaro A. et al. Development and validation of a composite disease activity score for juvenile idiopathic arthritis. Arthritis Rheum 2009, 61:658. Jansen J, van Riel PLCM The disease activity score and the EULAR response criteria. Rheum Dis Clin N Am 2009, 35: 745. Landewé R et al. Twenty-eight joints count invalidate DAS the 28 remission definition owing to the omission of the lower extremity joints: a comparison with the original DAS remission. Ann Rheum Dis 2006, 65: 637. <h3>Disclosure of Interest</h3> None Declared
Abstract 2739: DNA repair genotype-phenotype correlation and interplay between different DNA repair pathways
Authors: Alessandra Allione, Simonetta Guarrera, Silvia Polidoro, Fabio Rosa, Fulvio Ricceri, Floriana Voglino, Alessia Russo, Cornelia Di Gaetano, Valeria Simonelli, Filomena Mazzei, Paola Porcedda, Claudia Giachino, Paolo Vineis, Eugenia Dogliotti, Giuseppe Matullo
Journal: Cancer Research (2011)

Abstract Individual DNA repair capacity is modulated by the genetic background to which hundreds of single nucleotide polymorphisms (SNPs) or haplotype combinations in DNA repair genes are likely to contribute. A large number of studies have been published on the association between DNA repair gene polymorphisms and cancer risk, whereas only few small studies investigated the relation between DNA repair phenotypic assays and cancer risk or DNA repair polymorphisms. In order to identify functional SNPs/haplotypes modulating DNA repair phenotypes and to investigate their potential impact on cancer risk, we have performed a genotype-phenotype correlation study evaluating levels of DNA damage and DNA repair capacity in blood cells treated at low doses of different DNA damaging agents. We investigated the association between genotypes/haplotypes and the DNA repair capacity measured with the following DNA repair phenotypic assays on cryopreserved lymphocytes from 225 healthy individuals: Comet assay after treatment with BPDE, phosphorylation of histone H2AX after treatment with γ-rays, OGG1 glycosylase activity, OGG1 and ERCC1 expression levels. Sixty-five DNA repair genes and a total of 768 SNPs have been selected and analysed on the 225 DNA samples by using a custom GoldenGate SNP chip (Illumina). Genotype-phenotype correlation analysis identified some new possible functional variants and haplotypes. We also tested gene-gene interactions, comparing results with existing prior knowledge from different publicly available databases and crossing functional evidence with information on gene expression levels and protein-protein interaction. A confirmation of some already described interplays between different DNA repair pathways have been obtained from SNP analysis and a suggestion of new possible cross-talks have been identified that need further experimental validation. Our results can contribute to identify subjects carrying combinations of less efficient DNA repair variants/haplotypes possibly at increased cancer risk or who can better benefit from anti-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 2739. doi:10.1158/1538-7445.AM2011-2739
SP0062 Imaging Biomarkers in Psoriasis for Predicting Developing PSA
Authors: E. Naredo
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> Psoriasis is a common chronic immune mediated skin disease. Psoriatic arthritis occurs in a variable, albeit considerable percentage of psoriatic patients which ranges from 10 to 30% depending on the studied population. Psoriatic arthritis may be present in different clinical forms whose major features are synovitis and/or enthesitis. In most patients, psoriasis precedes the clinical onset of the joint inflammatory disease. A number of studies have reported the presence of subclinical synovitis and enthesopathy detected by imaging techniques (e.g. MRI, ultrasound) in a higher percentage of psoriatic patients without musculoskeletal symptoms compared to controls. Some preliminary data on the predictive value of these imaging findings in relation to psoriatic arthritis development have been reported. This lecture offers an update of imaging modalities as biomarkers in psoriasis and psoriatic arthritis. <h3>Disclosure of Interest</h3> E. Naredo Grant/Research support from: UCB and MSD, Consultant for: Abbvie, Roche Farma, Bristol-Myers Squibb, Pfizer, UCB, General Electric Healthcare, and Esaote <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6110
Radionuclide Angiography and Ventilation/Perfusion Studies in Two Patients With Systemic Arterial Supply to the Basal Segment of the Left Lung
Authors: KAZUYOSHI SUGA, NAOFUMI MATSUNAGA, KAZUYA NISHIGAUCHI, SHIGERU YONESHIRO, AYAME SHIMIZU, KATSUYUKI TAKANO, GOUJI MIURA, AND ISAO ARIYOSHI
Journal: Clinical Nuclear Medicine (1997)

The findings of radionuclide studies in two adult men with systemic arterial supply to the basal segment of the left lung without sequestration are reported. Radionuclide angiography with Tc-99m human serum albumindiethylenetriamine showed that the lung was perfused by the systemic circulation rather than by the pulmonary artery. Ventilation and perfusion scans with Xe-133 and Tc-99m MAA showed a V/Q mismatch in this area, suggesting the presence of normal bronchial communication without a pulmonary arterial supply. These results also suggest the presence of a left-to-left shunt in the well-ventilated lung in this area. MRI and conventional angiography showed an aberrant artery arising from the descending thoracic aorta, supplying the basal segment of the left lung without a pulmonary artery. In both patients, left lower lobectomy showed normal alveobronchial structures without sequestration. Radionuclide angiography and ventilation/perfusion imaging appear to be reliable noninvasive methods for diagnosing this rare anomaly with a left-to-left shunt.
P989 A NOVEL SIMPLIFIED CHILD–TURCOTTE–PUGH SCORE FOR PROGNOSTIC ASSESSMENT AND THERAPEUTIC DECISION IN PATIENTS WITH HEPATOCELLULAR CARCINOMA
Authors: A. Vitale, A. El Nemr, T.-L. Huo, F. Trevisani, Y.-H. Lee, F. Piscaglia, U. Cillo, F. Farinati
Journal: Journal of Hepatology (2014)
A step too far
Authors: R. G. Twycross
Journal: BMJ (2012)

I agree that the sanctity of life law has gone too far.1 Unless this judgment is modified, it could “gradually and detrimentally distort healthcare provision, healthcare values, and common sense.”1 Why? Because although the judgment was specific to patients in a minimally conscious state, logically all decisions about withholding or withdrawing clinically …