tbuckley/cabot-search huggingface dataset:
Abstract 3881: Genetic alterations in intrahepatic cholangiocarcinoma- revealed by array CGH, SKY and gene expression microarray
Authors: Wen-Hui Weng, Lee-Cheng Tsao, Yeu-Jye Pang, See-Tong Pang, Chun-Nan Yeh
Journal: Cancer Research (2011)

Abstract Cholangiocarcinoma (CCA) is an adenocarcinoma of the biliary tract, which is considered to be an incurable and rapidly lethal disease. A major problem with CCA surveillance is the lack of reliable biomarkers, therefore, still less no significant aspects of client-centered therapy in clinical treatment so far. Here, we established a 25th week thioacetamide (TAA)-induced cholangiocarcinoma rat cell line model named Chang Gung CCA (CGCCA), aim to figure out the early alterations of cytogenetics, molecular and protein expressed characteristics of CCA. Array comparative genomic hybridization (aCGH) and Spectral karyotyping (SKY), gene expression microarray and immunohistochemistry were performed on either rat CCA tissues or CGCCA cell line in this study. Our results showed complicated alterations of genetic gain or loss on different chromosomal regions could be observed. The data compared with the gene expression profile, thirty-three genes aberrations could be further identified; for example, tumor metastasis-related genes ANXA1 and CLCA3, the genes MMP7 and MMP12 are related with tumor invasion, and proliferation-related genes PKM2 and OSMR have been pinpointed; The number of chromosome ranging between 50 to 56 diplody (2n); despite the apparently high incidence of chromosomal translocation was revealed by cytogenetic analyses, ring and/or giant rod marker chromosomes were detected in almost every CGCCA cells, and the genetic materials are mainly included chromosomes 4 and 8. Herein, we concluded ANXA1, CLCA3, MMP7, MMP12, PKM2 and OSMR genes could be considered as potential biomarkers for the risk of disease. Supernumerary ring or giant rod marker chromosomes could also be considered as a characteristic may be involved in the late stage of CCA. However, the genes involved in the tumorigenesis should be further investigated the function of the genes. In order to verify the clinical significance and potentially to be as therapeutic targets in the future, to confirm onto a series of human CCA tissues are necessary. 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 3881. doi:10.1158/1538-7445.AM2011-3881
Serotonin, Antiserotonins and Hypertension
Authors: Robert W. Wilkins
Journal: New England Journal of Medicine (1956)

SEROTONIN or 5-hydroxytryptamine (5-HT) (Fig. 1) has been the subject of a great deal of recent investigation and speculation. Two excellent reviews, one by Page1 and the other by Erspamer,2 both of whom have contributed important basic information, give the background of the recent interest. Serotonin is found in many tissues of the body but is particularly concentrated in the brain, the platelets of the blood and the mucosa of the gastrointestinal tract. It is an intense local vasoconstrictor, and its presence in platelets has been assumed to give them a styptic as well as a thrombotic function. Certainly within . . .
Abstract LB-322: A modified HER2/neu peptide vaccine (2L9V-GP2) demonstrates enhanced CD8+ T cell recognition and stimulation in breast cancer patients at high risk for recurrence
Authors: Ritesh Patil, Guy T. Clifton, Kevin Clive, Josh Tyler, Athina Zacharia, Yusuf Jama, Mohamed Mursal, Kathy Ciano, Jarrod P. Holmes, Elizabeth A. Mittendorf, George E. Peoples, Sathibalan Ponniah
Journal: Cancer Research (2010)

Abstract Introduction: The affinity between tumor-associated antigens and MHC Class I complexes directly affects the degree of CD8+ T cell (CTL) response. GP2 (IISAVVGIL, p654-662) is a HER2/neu-derived peptide, that has poor binding affinity to HLA-A2 (A2) and HLA-A3 (A3). We conducted a preclinical study to determine if amino acid substitutions in the GP2 peptide, predicted to increase binding affinity to A2 and A3, enhance CTL recognition and stimulation. Methods: Based on computer modeling algorithms (BIMAS, SYFPEITHI), two GP2 peptide variants were predicted to have higher binding affinity to A2: SPA-12(2L9V-GP2) and SPA-13(2L5L9V-GP2). Freshly isolated PBMCs were obtained from randomly chosen, disease-free, node positive (NP) and high risk node negative (NN) breast cancer (BCa) patients, who had completed standard adjuvant therapy and are enrolled in the E75 vaccine booster trial. Peptide-specific CD8+ T cells were measured by HLA-A2: IgG dimer (A2 pts) and by interferon-γ ELISPOT (A2, A3 pts) assays. Groups were compared by t-test (dimer) and Mann-Whitney U (ELISPOT) tests. Results: Thirty-five A2 (21 NP, 14 NN) and thirteen A3 (13 NP) samples were included in the study. Among A2 pts, the mean level of SPA-12-specific CTLs was greater than the GP2- (2.8±0.3% vs. 1.7±0.1%, p&amp;lt;0.001) and SPA-13-specific CTLs (2.8±0.3% vs. 1.1±0.1%, p&amp;lt;0.001). The level of SPA-13-specific CTLs was less than GP2-specific CTLs (p&amp;lt;0.001). For both A2 and A3 pts, the median number of IFN- producing cells was greater in response to SPA-12 (144, range 0-799 spots/105 cells) compared to GP2 (88, range 0-432 spots/105 cells, p=0.03) and SPA-13 (0, range 0-344 spots/105 cells, p&amp;lt;0.001). Again, the response to SPA-13 was less than GP2 (p=0.001). In addition, the NP A2 pts demonstrated a more robust CD8+ T cell response to SPA-12 compared to the NNs, both by HLA-A2: IgG dimer (3.2±.5 vs 2.2±0.2, p=0.05) and ELISPOT assay (223, range 0-799 vs 65, range 0-548 p=0.003). Nodal status did not have any significant bearing on the responses to GP2 and SPA-13. Conclusion: The substituted sequences SPA-12 (2L9V-GP2) and SPA-13 (2L5L9V-GP2), both have higher predicted binding affinity to A2 and A3 than GP2. While SPA-12 showed significantly increased recognition and functional CTL responses compared to GP2, SPA-13 demonstrated lower responses. These data suggest that SPA-12 may be a more effective cancer vaccine than GP2, particularly in NP BCa patients. 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-322.
THU0136 Cardiovascular safety findings in rheumatoid arthritis patients treated with tofacitinib (CP-690,550), a novel, oral jak inhibitor:
Authors: C. Charles-Schoeman, P. Wicker, U. Sechtem, M.A. Gonzalez-Gay, S. Wood, M. Boy, J. Geier, D. Gruben, K. Soma, R. Riese, J. Bradley
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Tofacitinib is a novel, oral Janus kinase inhibitor being investigated as a targeted immunomodulator and disease-modifying therapy in rheumatoid arthritis (RA). <h3>Objectives</h3> To evaluate the cardiovascular (CV) event rates and changes in blood pressure (BP) in the tofacitinib Phase 3 (P3) and long-term open-label extension (LTE) studies. <h3>Methods</h3> Five P3 studies in patients (pts) with inadequate response to nonbiologic/biologic disease-modifying anti-rheumatic drugs (DMARDs) and 2 LTE studies were included. Tofacitinib was administered as monotherapy or with background nonbiologic DMARDs, predominantly methotrexate. One P3 study included adalimumab (ADA) as active control. An independent CV Safety Endpoint Adjudication Committee performed blinded adjudication of deaths, potential major adverse CV events (MACE), and events of congestive heart failure (CHF). MACE was defined as CV death and non-fatal CV events. <b>Results:</b> MACE IRs (per 100 pt-y) in placebo (PBO) and tofacitinib groups in P3 were low. IR in the LTE studies in the tofacitinib All Dose group (0.19) was lower than in P3 (0.57). IRs of CHF in tofacitinib were low. In P3, mean changes from baseline at Month 3 for systolic and diastolic BP, respectively, were -0.1 mmHg and -0.8 mmHg for PBO and -0.2 and 0.3 mmHg for tofacitinib. Mean BP changes at Months 6 and 12 and in the LTE studies remained stable. <h3>Conclusions</h3> Incidence rates of MACE were similar across groups in P3 with lower rates in LTE, suggesting no increased risk over 3 years of follow up. Tofacitinib was not associated with clinically meaningful increases in BP. Although the number of events have been fewand longer observation periods are warranted, CV risk does not appear to be increased with tofacitinib treatment and rates of CV events are consistent with those observed among patients with RA of similar disease severity.<sup>1-3</sup> <h3>References</h3> Solomon DH et al. Circulation 2003; 107: 1303-1307; Solomon DH et al. Ann Rheum Dis 2006; 65: 1608-1612; 3. Nicola PJ et al. Arthritis Rheum 2006; 54: 60-67. <h3>Disclosure of Interest</h3> C. Charles-Schoeman Grant/Research support from: Pfizer Inc., Consultant for: Pfizer Inc., P. Wicker Consultant for: Pfizer Inc., U. Sechtem Consultant for: Pfizer Inc., M. Gonzalez-Gay Consultant for: Pfizer Inc., S. Wood Shareholder of: Pfizer Inc., Employee of: Pfizer Inc., M. Boy Shareholder of: Pfizer Inc., Employee of: Pfizer Inc., J. Geier Shareholder of: Pfizer Inc., Employee of: Pfizer Inc., D. Gruben Shareholder of: Pfizer Inc., Employee of: Pfizer Inc., K. Soma Shareholder of: Pfizer Inc., Employee of: Pfizer Inc., R. Riese Shareholder of: Pfizer Inc., Employee of: Pfizer Inc., J. Bradley Shareholder of: Pfizer Inc., Employee of: Pfizer Inc.
GLOBAL LONGITUDINAL STRAIN IS A PREDICTOR OF HEART FAILURE IN PATIENTS WITH ACUTE ANTERIOR WALL MYOCARDIAL INFARCTION
Authors: Sun-Hwa Lee, Sookyeong Song, Ji-Young Yoon, Yisik Kim, Lae Young Jung, Kyoung-Suk Rhee, Jeikeon Chae, Wonho Kim, Jaeki Ko
Journal: Journal of the American College of Cardiology (2016)
AB1387 Reasons for discontinuation of subcutaneous biologic therapy in the treatment of rheumatoid arthritis: A patient perspective:
Authors: S. Bolge, A. Goren, N. Tandon
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Several factors may lead to discontinuation of biologic therapies by patients with rheumatoid arthritis (RA). The role of these factors in discontinuation of therapy should be examined to determine how best to achieve successful and uninterrupted treatment. <h3>Objectives</h3> To examine reasons for discontinuation of subcutaneous (SQ) anti-TNF treatment in the past twelve months from the RA patient perspective. <h3>Methods</h3> Data were collected in Spring 2011 using self-reported, internet-based questionnaires. Study inclusion criteria were: RA diagnoses; discontinued a SQ anti-TNF medication (adalimumab, certolizumab, etanercept, or golimumab) within the past 12 months; aged ≥18 years; reside in the United States; consented to participate. Patients reported primary and other reasons for discontinuation. Patients who discontinued more than one SQ anti-TNF in the past 12 months reported on the one most recently discontinued. <h3>Results</h3> Completed questionnaires were analyzed for 250 patients. The majority were female (72.8%) and white (80.8%); median age was 51 years. More patients most recently discontinued etanercept (43.6%) or adalimumab (39.2%) than certolizumab (9.6%) or golimumab (7.6%). When prompted about the primary reason for discontinuation, lack of effectiveness (40.8%) was most often cited, followed by injection experience (18.4%). Combining prompted primary and other reasons for discontinuation, 60.8% reported lack of effectiveness and 40.8% reported injection experience. These injection experience reasons included: pain/burning/discomfort after injection (14.4%); pain/burning/discomfort during injection (13.2%); injection reactions such as redness/swelling after injection (12.4%); dislike self injection (11.6%); dislike frequency of injection (10.4%); fearful of injection/needles (6.8%). <h3>Conclusions</h3> From the patient perspective, there are remaining unmet needs related to effectiveness and injection experience with SQ anti-TNF medications, which lead to discontinuation. Newer treatment options may address some of these unmet needs. These results demonstrate the importance of including the patient perspective when making treatment decisions. <h3>Disclosure of Interest</h3> S. Bolge Employee of: Janssen Scientific Affairs, LLC, A. Goren Consultant for: Janssen Scientific Affairs, LLC, N. Tandon Employee of: Janssen Scientific Affairs, LLC
PTU-086 Ulcerative Colitis (uc) And Anti-tumour Necrosis Factor (a-tnf) Therapy; A Single Unit’s Real World Experience: Abstract PTU-086 Table 1
Authors: H Steed, A Rowlinson, F Leslie
Journal: Gut (2014)

<h3>Introduction</h3> Prescription of a-TNF therapy in UC in the UK is limited to acute severe colitis by NICE. Increasingly physicians are under pressure from patients to offer an alternative to the traditional limited therapeutic options and this has resulted in the drug being used in the subacute setting, as it is in other countries. <h3>Methods</h3> A retrospective review of all patients receiving a-TNF for UC up until December 2012. <h3>Results</h3> Twenty-one patients have received a-TNF therapy for UC. Five are currently on a-TNF treatment, 4 of whom commenced in the last 12 months. Twelve were discontinued for non-response, 1 for funding, 1 for remission, 2 for side effects and 1 at the patient’s request. Two were switched. Response to the agents are shown in Table 1. Thirteen received infliximab as first agent, eight had adalimumab. Seven were on other immunomodulators at the time of commencing a-TNF and 11 were intolerant to immunomodulators. Three had a-TNF for acute colitis, 15 for subacute colitis and data unknown for 3 patients. Currently 3 patients are in clinical remission, 11 had surgery and 7 have active disease (with 2 strongly recommended to have surgery). Twelve patients had steroids while on a-TNF. Mean time on a-TNF was 4.7 months. <h3>Conclusion</h3> a-TNF use in UC does not appear to be very effective in this context, with 62% having or requiring surgery and 60% requiring concurrent steroids. To make this therapy more cost effective in this patient group more work is needed to identify patients likely to be responders. <h3>Disclosure of Interest</h3> None Declared.
Abstract P2-01-04: Long term independent prognostic impact of circulating tumor cells detected before neoadjuvant chemotherapy in non-metastatic breast cancer: 70 months analysis of the REMAGUS02 study
Authors: F-C Bidard, S Delaloge, S Giacchetti, E Brain, P de Cremoux, A Vincent-Salomon, M Marty, J-Y Pierga
Journal: Cancer Research (2012)

Abstract Background: Circulating tumor cells (CTCs) isolated by CellSearch® from peripheral blood of metastatic breast patients have been shown as strong independent prognostic factor for progression-free and overall survival. With this technique, the REMAGUS02 prospective multicentric study was the first to report that CTC detection (≥1CTC/7.5ml) before and/or after neoadjuvant chemotherapy was independently associated with distant metastasis-free survival (DMFS, 18 months follow-up, Pierga CCR 2008) and with overall survival (OS, 36 months follow-up, Bidard Ann Oncol 2010). Patients and Methods: In 115 non-metastatic patients diagnosed with large operable or locally advanced breast cancer, we prospectively detected CTC using the CellSearch system before and after neoadjuvant chemotherapy in the REMAGUS02 trial (Pierga, BCRT 2010). For this report, survival analyses were performed at a median follow-up of 70 months. Results: After a median follow-up of 70 months, 20 distant metastatic relapses and 14 deaths have been observed among the 115 patients included. CTC detection before chemotherapy (in 23% of patients) is an independent prognostic factor for both DMFS [p = 0.03, relative risk (RR)=3.2] and OS [p = 0.05, RR = 3.7] in multivariate analyses, together with triple negative tumor status. At long-term, CTC detection after chemotherapy (17%) had no clear prognostic significance (p = 0.15 and 0.22, respectively). Complete pathological response as well as tumour size and all other variables tested did not appear as predictive in this model. Conclusions: Baseline CTC detection is a new independent prognostic factor in the neoadjuvant setting, and is, in this trial, superior to pathological tumor response to predict the survival of non-metastatic breast cancer patients. We confirm therefore our previous results reported with shorter follow-up. Supported by PHRC AOM/2OO2/02117, Pfizer inc., Roche, sanofi-aventis. ISRCTN10059974 Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-01-04.
Abstract P2-16-13: Phase II Open Label Trial Bevacizumab in Combination with Paclitaxel and Gemcitabine as First Line in Patients with HER-2 Negative Recurrent or Metastatic Breast Cancer (AVALUZ): First Analysis
Authors: J Salvador, A Jaen, E Ciruelos, M Codes de Villena, M Gil, A Murias, A Galan, J de la Haba, C Jara, J Bayo, JM Baena, J Casal, JR Mel, I Blancas, E Gonzalez, D Perez, L. Manso
Journal: Cancer Research (2010)

Abstract Background: The combination of bevacizumab with taxanes, capecitabine or anthracyclines has shown increased progression-free survival in patients with metastatic breast carcinoma. The aim of this study is to evaluate the efficacy and toxicity profile of the combination of bevacizumab with gemcitabine and paclitaxel, providing a preliminary analysis of response in patients included for whom at least one response assessment and the toxicity experienced in all patients treated. Methods: A Phase II multicenter, national, open-label study in patients diagnosed of recurrent or metastatic HER-2 negative breast carcinoma, treated with first-line bevacizumab 10 mg/kg, paclitaxel 150 mg/m2 and gemcitabine 2000 mg/m2 day 1 and 15 c/28d until disease progression, unacceptable toxicity, or medical decision. This abstract evaluates efficacy by the response rate and the toxicity profile of the combination in all cycles of all patients included. The primary end-point of the study is PFS. Toxicity is evaluated according to NCI CTC v 3.0 criteria. Results: From January 2009 to December 2009, 82 evaluable patients were recruited in 23 sites, with at least one response assessment available in 69. Median age 51.5 (26-81), ER+ 59 pts, PR+ 51 pts, triple negative patients 16 and previous chemotherapy (neoadj or adj) 58 pts. Of the 69 pts with response assessment, the last assessment is in cycle 3 for 31.88% of patients, cycle 6: 33.33%, cycle 9: 4.35%, cycle 12: 1.45% and at the end of treatment 29%. The median cycles administered per patient is 6 (1-14) and the relative median dose intensity is 0.93 for bevacizumab, 0.91 for paclitaxel, and 0.93 for gemcitabine. The overall response obtained was 69.57%, with a clinical benefit of 89.86% (CR 8.7% (6), PR 60.87% (42), SD 20.29%, and DP 10.14%). Of the 82 patients with a median follow-up of 7.19 m (0.16-13.98), grade 3-4 toxicity affected 41%, with treatment discontinuation for adverse events in 19.51%. Eighteen SAEs were reported: pyrexia (4), infection at catheter site (2), urine infection and a single case of angor, hypertension, pulmonary embolism, pleural effusion, febrile neutropenia, neutropenia, vomiting, diarrhoea, dehydration, atrial fibrillation, and dizziness. Toxicity was generally easily controlled. Conclusions: Although data from the primary study endpoint (PFS) are not yet available, the treatment regimen obtained a high overall response in patients treated and was well tolerated by this patient group. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-16-13.
Abstract 837: Novel sulindac derivatives that inhibit colon cancer growth by a COX independent mechanism involving PDE5 inhibition and the suppression of nuclear β-catenin levels
Authors: Jason D. Whitt, Adam B. Keeton, Heather N. Tinsley, Bernard D. Gary, Nan Li, Bini Mathew, Robert C. Reynolds, Gary A. Piazza
Journal: Cancer Research (2011)

Abstract Many colon cancers harbor APC mutations that prevent the proteosomal degradation of oncogenic β-catenin. Previous studies have found that certain nonsteroidal anti-inflammatory drugs (NSAIDs) have the ability to reduce nuclear levels of β-catenin and inhibit tumor cell growth through a cyclooxygenase (COX)-independent mechanism, which might be responsible for their cancer chemopreventive activity. A potential mechanism may involve cGMP phosphodiesterase (PDE) inhibition and the activation of protein kinase G (PKG). In this study we evaluated over 500 novel sulindac derivatives for colon tumor cell growth inhibitory activity. Select compounds were also evaluated for COX and cGMP PDE inhibitory activity to determine which activity is associated with colon tumor cell growth inhibition and ability to suppress nuclear β-catenin levels. A subset of derivatives was identified that displayed reduced COX-1 and COX-2 inhibitory activity, yet increased potency to inhibit the growth of several colon tumor cell lines (HT29, HCT116, SW480, and COLO741) with IC50 values of 2-10 µM compared with IC50 values of 80-110 µM for the parent compound, sulindac sulfide (SS). Certain derivatives also displayed increased potency to inhibit recombinant phosphodiesterase 5 (PDE5), which appears to be the isozyme responsible for the cGMP PDE inhibitory activity of SS. Treatment of colon tumor cells with such compounds also increased the phosphorylation of vasoactive stimulated protein (VASP), a known PKG substrate. Furthermore, nuclear levels of β-catenin decreased within the same time period as PKG activation, which is consistent with previous reports suggesting that PKG can phosphorylate β-catenin to induce proteosomal degradation. Together, these data indicate that sulindac can be chemically modified to eliminate COX inhibitory activity while enhancing its ability to inhibit colon tumor cell growth. We conclude that the suppression of nuclear β-catenin levels by SS is independent of COX inhibition and that novel derivatives can be developed with improved antineoplastic activity while reducing the toxicities associated with COX inhibition. Funding provided by NIH/NCI grants CA131378 and CA148817. 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 837. doi:10.1158/1538-7445.AM2011-837
Assessment of minimal residual disease (MRD) in CBFbeta/MYH11-positive acute myeloid leukemias by qualitative and quantitative RT-PCR amplification of fusion transcripts
Authors: A Guerrasio, C Pilatrino, D De Micheli, D Cilloni, A Serra, E Gottardi, A Parziale, F Marmont, D Diverio, M Divona, F Lo Coco, G Saglio
Journal: Leukemia (2002)
Covered self-expanding metal stents for transmural drainage of infected pancreatic fluid collections: don't sell the skin till you have caught the bear or at least spotted the animal
Authors: W. Laleman, S. Van der Merwe
Journal: Endoscopy (2012)

We read with interest the article by Fabbri et al. entitled “Endoscopic ultrasound-guided transmural drainage of infected pancreatic fluid collections with placement of covered self-expanding metal stents: a case series” [1]. The authors state that from their experience in 18 patients endoscopic ultrasound-guided transmural drainage (EUS-GTD) of (infected) pancreatic fluid collections using covered self-expanding metal stents (CSEMSs) is easier, faster, and safer, and likely to be more cost-effective.