tbuckley/cabot-search huggingface dataset:
Abstract LB-31: A snapshot of the expression signature of androgen receptor splicing variants and their distinctive transcriptional activities
Authors: Rong Hu, William B. Isaacs, Jun Luo
Journal: Cancer Research (2011)

Abstract Objectives: Multiple androgen receptor (AR) splicing variants implicated in ligand-independent AR signaling have been characterized. These variants are expressed in hormone naïve prostate cancers, and elevated in castration-resistant prostate cancers (CRPC), supporting their potential as biomarkers and therapeutic targets for advanced prostate cancer. The diversity and complexity of AR splicing variants however are not fully understood, raising the need to generate a comprehensive expression signature of AR variants, and to address the relative importance of the individual variants that may confer the castration resistant phenotype. Methodology: A modified RNA amplification method, termed selective linear amplification of sense RNA (SLASR), was developed to amplify all AR transcripts containing AR exon 3. Amplified AR transcripts from CRPC specimens were profiled using expression microarrays with probes tiled across the human AR gene locus. Primers corresponding to novel expression peaks in the AR locus were designed to amplify and decode the splicing junctions. Coding sequences for a subset of selected AR variants were cloned into expression vectors and assessed for their transcriptional activities. Quantitative RT-PCR was used to determine their in vivo expression patterns in an expanded set of clinical specimens. Preliminary data: Tiling microarray results revealed a molecular portrait of both canonical and cryptic AR exons across the human AR locus. In addition to expression peaks in AR intron 3, a novel AR exon, termed exon 9, was discovered. Exon 9 was spliced into multiple novel AR variants. Different AR splicing variants were functionally distinctive, with some demonstrating constitutive activity while others were conditionally active. Conditionally active AR-Vs may activate AR signaling depending on the cellular context. AR variant functions however did not appear to depend on the full-length AR. AR variants demonstrated patterns of expression change in clinical prostate tumor specimens consistent with their role in castration-resistant progression. This study provided the first unbiased snapshot of the AR variant signature consisting of multiple AR variants with distinctive functional properties. Our results suggest that some AR variants previously considered to be inactive may confer the castration resistance phenotype depending on the cellular context. If further confirmed, the aggregate function of multiple AR variants may compensate for the low abundance of individual variants in clinical specimens relative to the full-length AR. 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 LB-31. doi:10.1158/1538-7445.AM2011-LB-31
Abstract 3035: Bone morphogenetic proteins signal through Smad2 and Smad3 to regulate cell migration and proliferation
Authors: Alisha Holtzhausen, Tam How, Bradley C. Gersh, Gerard C. Blobe
Journal: Cancer Research (2012)

Abstract The TGF-β superfamily consists of a large number of growth factors, including transforming growth factor-β (TGF-β) and bone morphogenetic proteins (BMPs) that regulate cellular proliferation, differentiation, invasion, migration and apoptosis. TGF-β activates the transcription factors Smad2/3, as well as Smad1/5/8, while BMP stimulation results in the activation of Smad1/5/8. Unexpectedly, we have demonstrated that BMP family members, including BMP2, 3, 4, 7, 9 and GDF5 can also induce Smad2/3 phosphorylation and downstream gene transcription in ovarian, pancreatic and breast cancer cell lines. BMP2-induced Smad2 phosphorylation can be attenuated by expression of dominant negative TβRII or shRNA-mediated knockdown of TβRII, while BMP2-induced Smad3 phosphorylation can be attenuated by expression of dominant negative BMPRII or shRNA-mediated knockdown of BMPRII, suggesting different mechanisms of BMP-mediated activation of Smad2 and Smad3. BMP2-induced Smad1, Smad2 and Smad3 phosphorylation increase cell invasion, migration and proliferation, respectively. BMP stimulated Smad2/3 phosphorylation suggests that BMP-mediated effects on cancer progression may be regulated, in part, through these novel signaling pathways. Current studies are focused on further elucidating the role of BMP-induced Smad2 and Smad3 phosphorylation on human cancer progression. 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 3035. doi:1538-7445.AM2012-3035
AI-17 * ROBO2-SLIT1 SIGNALING IMPLICATED IN GLIOMA INVASION
Authors: A. Kerstetter-Fogle, P. Harris, D. Bonda, J. Barnholtz-Sloan, M. Couce, A. Sloan
Journal: Neuro-Oncology (2014)

Glioblastomas (GBM) account for 54.3% of newly diagnosed glioma in the United States each year. Their rapid growth and invasion into neuronal parenchyma renders them devastating, with limited treatment options and median survival of only 12-15 months. Although there have been numerous studies of molecular aberrations in GBM, few have characterized signaling pathways specifically promoting invasion. The roundabout (Robo) family of transmembrane receptors, and their Slit protein ligands, have been demonstrated to be involved in neuronal migration and outgrowth during CNS development and have also been implicated in various cancers. We hypothesized that the Slit-Robo signaling pathway may promote GBM invasion as well. We reviewed various databases and performed IHC, PCR and Western blot of the Robo-Slit family members from GBM samples obtained from our IRB approved biorepository. Analysis of the NCI Rembrandt database indicates poorer survival among glioma patients with 2 fold or greater overexpression of the Robo2 gene (17.1 months versus 37.4 months; p = 1.42E-4). Robo-Slit signaling from distinct geographic regions of GBM tumor, identified prospectively on pre-operative MRI, and sampled using stereotactic image-guided biopsies from these preselected tumor regions, revealed significant differences in Robo-Slit levels in regions characterized by tumor invasion. Tissue samples from 6 GBM and 3 control patients, revealed a 2-5-fold increase in Robo-Slit family members in GBM by IHC, and quantitative RT-PCR and Western confirmed a 101-fold increase in Robo2 mRNA expression, as well as a 19.8 fold increase in Robo2 protein relative density in GBM (respectively) compared to normal brain parenchyma in regions of tumor invasion. Slit1 and Slit 2 also demonstrated co-localization in a majority of tumor cells. These data suggest a complex and heterogeneous tumor microenvironment and implicate Robo-Slit axis signaling in GBM invasion, making it a potentially attractive therapeutic target.
From the authors:
Authors: S. Singh, Y.K. Loke
Journal: European Respiratory Journal (2010)

From the authors :

We agree with M.A. Puhan's letter regarding the need for full reporting of important clinical end-points and appropriate statistical analysis in randomised controlled trials in chronic obstructive pulmonary disease, the need for which is demonstrated by our robust meta-analysis on cardiovascular outcomes 1.

First, the manufacturers of other inhaled bronchodilators should provide comprehensive listings of adverse events similar …
Intraperitoneal Cisplatin plus Intravenous Cyclophosphamide versus Intravenous Cisplatin plus Intravenous Cyclophosphamide for Stage III Ovarian Cancer
Authors: David S. Alberts, P.Y. Liu, Edward V. Hannigan, Robert O'Toole, Stephen D. Williams, James A. Young, Ernest W. Franklin, Daniel L. Clarke-Pearson, Vinay K. Malviya, Brent DuBeshter, Mark D. Adelson, William J. Hoskins
Journal: New England Journal of Medicine (1996)

Intravenous platinum-based chemotherapy is the standard primary therapy for advanced ovarian cancer. We conducted a phase 3 trial to compare the effects of intraperitoneal and intravenous cisplatin on the survival of women with previously untreated, stage III, epithelial ovarian cancer.The patients underwent an initial exploratory laparotomy and resection of all tumor masses larger than 2 cm. Within four weeks after surgery, six courses of intravenous cyclophosphamide (600 mg per square meter of body-surface area per course) plus either intraperitoneal cisplatin (100 mg per square meter) or intravenous cisplatin (100 mg per square meter) were administered at three-week intervals.Of 654 randomized patients, 546 were eligible for the study. The estimated median survival was significantly longer in the group receiving intraperitoneal cisplatin (49 months; 95 percent confidence interval, 42 to 56) than in the group receiving intravenous cisplatin (41 months; 95 percent confidence interval, 34 to 47). The risk of death was lower in the intraperitoneal group than in the intravenous group (hazard ratio, 0.76; 95 percent confidence interval, 0.61 to 0.96; P = 0.02). Moderate-to-severe tinnitus, clinical hearing loss, and neuromuscular toxic effects were significantly more frequent in the intravenous group.As compared with intravenous cisplatin, intraperitoneal cisplatin significantly improves survival and has significantly fewer toxic effects in patients with stage III ovarian cancer and residual tumor masses of 2 cm or less.
Abstract 4507: Deletion of 9p21.3/p16/CDKN2A is associated with poorer survival in primary central nervous system (PCNSL) lymphoma independent of 6q22 effect. A study facilitated by the Surveillance, Epidemiology and End Results Tissue Repository Program (SEER TRP)
Authors: Brian Patrick O'neill, Paul A. Decker, William R. Macon, Ellen D. McPhail, Mark Law, James R. Cerhan
Journal: Cancer Research (2012)

Abstract Objective. Molecularly distinct PCNSL signatures with divergent clinical behavior are now recognized. Implied within this heterogeneity are mechanisms for treatment response and pattern of failure. Recent cytogenetic and genomic studies demonstrated influences of select chromosomal regions on outcome to treatment and survival. These included genetic and epigenetic alterations affecting CDKN2A (9p21.3) that distinguished PCNSL from its systemic counterpart. We now report that deletion of 9p21.3/p16 is associated with a negative effect on survival. Methods and Patients. Well-annotated and population-based formalin fixed paraffin embedded (FFPE) patient samples were sourced from the SEER TRP. Specimens were retrieved from the Hawaii, Iowa and Los Angeles County (LA Co) tissue repositories. “Home Brew” fluorescent in situ hybridization (FISH) probes for BCL6, and ptpr-α were prepared according to a standard protocol (Cady et al. J Clin Oncol 2008;26:4814-9). FISH probes for 9p.21 were prepared similarly and then compared to a commercially available probe. Survival was based on the SEER TRP clinical annotations. Results. Thirty five patients were sourced - twelve from Iowa, 13 from Hawaii, and 10 from LA County. The test cohort was 23 from Iowa and Hawaii; the FISH probe failed in 9 and three had insufficient remaining tumor for analysis. For the Iowa and Hawaii registries and for the registries combined the lack of FISH probe detection of 9p.21/p16 correlated with survival (p=0.0159) and was independent of BCL6 (p=0.8788) and ptpr-α (p=0.3724). Conclusion. Deletion of p16 confers a negative effect on survival of PCNSL patients and appears to be independent of treatment, age, BCL6 and ptpr-α status. These results need to be confirmed in a larger sample size. 9p21.3 detection by FISH in feasible in surgical specimens and may aid in the stratification of such patients into different and/or more intensive treatment regimens. 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 4507. doi:1538-7445.AM2012-4507
FACTORES RELACIONADOS CON LA CALIDAD DE LA PREPARACIÓN DEL COLON EN LA COLONOSCOPIA AMBULATORIA
Authors: I Grilo, L Gómez, E Gómez Delgado, V Aguado Álvarez, M Cañas, I Ruz Segura, R Navarro López
Journal: Endoscopy (2014)

Introducción: La calidad de la limpieza colónica es fundamental. En un 25% de las colonoscopias la preparación es subóptima siendo importante detectar factores relacionados.
883 PREDICTION OF RESPONSE TO PEGYLATED INTERFERON/RIBAVIRIN BY INTERLEUKIN 28B GENOTYPE IS MODIFIED BY SNPS AT MULTIPLE GENES IN HIV/HEPATITIS C VIRUS GENOTYPE 1/4-COINFECTED PATIENTS
Authors: K. Neukam, A. Caruz, P. Barreiro, A. Rivero-Juárez, D. Merino, M. Márquez, E. P'erez-Navarro, V. Soriano, A. Rivero, J.A. Pineda
Journal: Journal of Hepatology (2013)
TCTAP A-116 Comparison of Aortic Annulus Dimensions by Multidetecter Computed Tomography Between Japanese and European Patients Undergoing Transcatheter Aortic Valve Implantation. Results from the Japanese Multicenter Registry and European Single Center Cohort
Authors: Yusuke Watanabe, Hideyuki Kawashima, Ken Kozuma, Bernard Chevalier, Thierry Lefevre, Marie-Claude Morice, Masanori Yamamoto, Kentaro Hayashida
Journal: Journal of the American College of Cardiology (2015)
Somatization Disorder in Primary Care
Authors: Roberta A. Monson, G. Richard Smith
Journal: New England Journal of Medicine (1983)

The dilemma of the patient presenting with multiple somatic symptoms is a common one for the general physician. The patient may have a confusing, subtle presentation of a systemic illness, which the primary physician wants to identify in its early stages. However, the physician also needs to assess the likelihood that the patient's somatic problems represent one of the somatoform disorders, which, as defined by the Diagnostic and Statistical Manual, third edition (DSM III),1 include somatization disorder, hypochondriasis, psychogenic pain disorder, and conversion disorder. This paper reviews somatization disorder, a chronic psychiatric condition that begins before the age of . . .
Minimally invasive periodontal therapy for general practitioners
Authors: Mark I. Ryder, Gary C. Armitage
Journal: Periodontology 2000 (2016)

Abstract There remains a high prevalence of mild‐to‐moderate forms of periodontal diseases in both developed and developing countries. Although many periodontal specialty practices currently place strong emphasis on implant surgery, periodontal plastic surgery and esthetics, general dentists and hygienists have often assumed more responsibility than periodontal specialty practices for the diagnosis, treatment, assessment and maintenance, and possible referral, of their patients. To address these current trends and challenges, this volume of Periodontology 2000 presents a series of topics on the basic biological principles of periodontal disease, as well as on approaches to diagnosis, treatment planning and treatment, in what is called ‘conservative’ or ‘noninvasive’ periodontal therapy. These topics include risk assessment of the periodontal condition; reduction, elimination and/or control of etiologies and risk factors, including mechanical, antimicrobial and host‐modulation approaches; considerations for evaluation of clinical outcomes based on treatment approaches; and selected topics in laser therapy, halitosis and gingival recession.
AB0063 Serum Cytokine Profiles in Patients with Takayasu's Arteritis
Authors: F. Alibaz-Oner, S. Yentur, G. Saruhan-Direskeneli, H. Direskeneli
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> Laboratory assessment of disease activity is one of the main difficulties in patients with Takayasu9s arteritis (TAK), during follow-up. To date, no biomarker is validated for clinical activity in TAK. In this study, we aimed to investigate serum GM-CSF, IL-6, IL-8, IL-10, IL-18 and IL-23 levels and their correlations with disease activity in patients with TAK. <h3>Methods</h3> The study included 74 patients (age: 41.8±13.5 years, F/M: 64/10) with TAK fulfilling ACR criteria and 42 age and sex-matched healthy controls (age: 38.1±7.4 years, F/M: 38/4). TAK patients were evaluated by physician9s global assessment (PGA; active/inactive) and by Kerr et al. definition (if available in the current visit) in terms of clinical activity. Fifty-one of 74 patients had a follow-up visit. Commercial ELISA kits were used for the measurement of serum GM-CSF, IL-6, IL-8, IL-10, IL-18 and IL-23. ESR and CRP levels were also measured. <h3>Results</h3> At baseline, 37 (50%) patients were active according to PGA. Kerr9 activity criteria were available for 62 patients and 24.2% (n=15) of these were active. Serum IL-8 and IL-18 levels were significantly higher in patients with TAK, whereas GM-CSF, IL-6, IL-10, IL-23 levels were similar to healthy controls. There was no difference between active and inactive patients regarding any cytokine level. ESR significantly correlated with IL-23 and CRP with IL-18 levels. Serum IL-6, IL-8 and IL-10 levels were significantly higher in patients taking corticosteroid therapies. In the follow-up visit, clinical activity rate decreased to 19.6% from 50% according to PGA. IL-8 levels significantly decreased and IL-23 levels significantly increased in follow-up compared to baseline. <h3>Conclusions</h3> We found significantly increased IL-8 and IL-18 level in patients with TAK and IL-18 levels correlated with CRP. IL-8 levels significantly decreased in the follow-up together with a decrease in the rate of clinical activity. These findings suggest that IL-8 and IL-18 might be important mediators for TAK pathogenesis and their blockage might be new therapeutic approaches. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3382
P10 INTERFERON LAMBDA 4 (IFNL4) POLYMORPHISM PREDICTS RESPONSE TO HEPATITIS C TREATMENT AFTER LIVER TRANSPLANTATION
Authors: C. Fernández-Carrillo, P. González, G. Crespo, M. Coto-Llerena, M. Navasa, X. Forns, S. Pérez-del-Pulgar
Journal: Journal of Hepatology (2014)
Improved Prognostic Value of Standardized Uptake Value Corrected for Blood Glucose Level in Pancreatic Cancer Using F-18 FDG PET
Authors: Sang Mi Lee, Tae-Sung Kim, Jeong Won Lee, Seok-Ki Kim, Sang-Jae Park, Sung-Sik Han
Journal: Clinical Nuclear Medicine (2011)

The purpose of this study was to determine the effect of blood glucose level correction on pancreatic cancer prognosis predictions after curative resection using F-18 fluorodeoxyglucose positron emission tomography (FDG PET).We enrolled 43 patients with pancreatic cancer who underwent preoperative FDG PET. Patient outcomes were categorized according to cancer recurrence in the clinical period. Maximum standardized uptake values (SUVmax) of tumors were measured using FDG PET, and blood glucose-corrected SUV (SUVgluc) was calculated as SUVmax × blood glucose level/100.Pancreatic cancer recurrence was observed within 9 months in 24 of 43 patients. SUVgluc, but not SUVmax, was significantly higher in the recurrence group than in the nonrecurrence group. Receiver operating characteristic analysis revealed that SUVgluc of 4.8 and SUVmax of 3.0 were the best cutoff values for predicting tumor recurrence. The 9-month recurrence-free survival rates were 72.3% for patients with SUVgluc ≤ 4.8, 23.5% for patients with SUVgluc >4.8, 75.0% for patients with SUVmax ≤ 3.0, and 45.0% for patients with SUVmax >3.0. SUVgluc was determined to be a significant predictive factor for tumor recurrence, along with differentiation, whereas SUVmax was not.SUVgluc on FDG PET aids in better predicting the prognosis of patients with pancreatic cancer after curative resection than does SUVmax without correction.
Abstract 3434: Thromboxane a2 receptor beta is induced by the epithelial to mesenchymal transition of breast cancer cells and contributes to breast cancer motility and metastasis
Authors: Xuejing Zhang
Journal: Cancer Research (2011)

Abstract Previous studies in our lab showed that thromboxane a2 receptor (TP) activation has profound effect on tumor cell cytoskeleton and contraction through activation of RhoA and depletion of TP reduces the metastatic dissemination of breast cancer cells in vivo. We report here that TP-beta expression is induced during epithelial-mesenchymal transition (EMT) and its activation is required for efficient migration and invasion of breast cancer cells. Elevated TP-beta expression is found associated with metastasis in tissues obtained from breast cancer patients. Breast cancer cell lines with high TP-beta expression present more malignant phenotype than the cells with low or no TP-beta expression. It is known that TP-alpha and TP-beta expressions are under the control of different promoter P1 and P3, respectively. Downregulation of E-cadherin in immortalized human mammary epithelial cells (Rao1) and breast cancer cells (MCF7) induces morphological changes of the cells to the mesenchymal type and upregulation of transcription factors that regulate EMT. Interestingly, TP-beta expression and P3 promoter activity are increased in the E-cadherin knock down cells, in contrast the level of TP-alpha remains unchanged. Further, beta-catenin/Tcf/LEF complexes are found to bind to and activate P3 promoter. Finally, a TP-beta specific inhibitor CAY10535 blocks the increased migration/invasion ability of MCF7 cells that is triggered during EMT. Together, these results indicate that beta-catenin released from membrane E-cadherin binding during EMT stimulates TP-beta expression by activating P3 promoter activity together with Tcf/LEF complexes and TP-beta activation enables enhanced migratory capacity, invasiveness of breast cancer cells. 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 3434. doi:10.1158/1538-7445.AM2011-3434
Abstract LB-471: Upregulation of miR-196a and HOTAIR is associated with the malignancy of gastrointestinal stromal tumors
Authors: Hiromu Suzuki, Masanori Nojima, Reo Maruyama, Eiichiro Yamamoto, Kohzoh Imai, Yasuhisa Shinomura
Journal: Cancer Research (2012)

Abstract Although dysregulation of microRNA (miRNA) expression is a common feature of human malignancies, its involvement in gastrointestinal stromal tumors (GISTs) is not fully understood. In the present study, we aimed to identify miRNAs associated with the malignant potential of GISTs. miRNA microarray analysis enabled us to detect the frequent upregulation of miR-196a in high-risk GISTs. Quantitative RT-PCR analysis of 56 fresh frozen and 100 formalin-fixed paraffin-embedded (FFPE) specimens confirmed that overexpression of miR-196a is associated with a high-risk grade, metastasis and poor survival among GIST patients (hazard ratio, 9.1; P &amp;lt; 0.001). The miR-196a genes are located within the HOX gene clusters, and gene expression microarray analysis revealed that HOXC genes and a large intergenic non-coding RNA (lincRNA), HOTAIR, were concurrently upregulated in GISTs overexpressing miR-196a. Elevated HOTAIR expression was also strongly associated with the high-risk category, metastasis and poor clinical outcome of GISTs (hazard ratio, 9.0; P = 0.034). RNAi-mediated knockdown of HOTAIR suppressed the invasiveness of GIST cells, and induced a significant change in the expression profile of genes that included previously reported HOTAIR target genes. This is the first report of concurrent overexpression of HOX genes and collinear non-coding RNAs in human malignancy, and our data suggest that miR-196a and HOTAIR could be useful biomarkers and novel therapeutic targets in malignant GISTs. 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 LB-471. doi:1538-7445.AM2012-LB-471