tbuckley/cabot-search huggingface dataset:
Abstract B55: The impact of inactivation of p53 and PTEN tumor suppressors on promotion and progression of human non-small cell lung carcinoma
Authors: Tijana Andjelkovic, Jasna Bankovic, Vedrana Milinkovic, Ana Podolski, Sabera Ruzdijic, Nikola Tanic
Journal: Cancer Research (2009)

Abstract Lung cancer is the major cause of cancer-related death worldwide and the five-year survival rate is not improving significantly, remaining at about 15% for all stages. Inactivation of p53 and PTEN (phosphatase and tensin homolog deleted on chromosome 10) tumor suppressors are molecular events highly related to the pathogenesis of lung cancer, particularly to non-small cell lung carcinoma (NSCLC). However, we still do not have clear image of the sequence of events in NSCLC promotion and progression, that is, whether inactivation of either of these tumor suppressors is early or late event and what the impact of these events is on NSCLC pathogenesis and patients survival. Therefore, we analyzed mutational inactivation of p53 and inactivation of PTEN by loss of heterozygosity (LOH) in 30 NSCLC patients and correlated obtained data with histopathological parameters that are indicators of initiation and progression of the disease: histological subtype, tumor grade, tumor stage, lymph node invasion and necrosis. PCR-single strand conformation polymorphism (PCR-SSCP) analyses revealed and sequencing procedures confirmed that 33.3% of patients had mutationaly inactivated p53 while fragment analysis of PTEN showed that 43.3% had inactivated PTEN by LOH. In total population of analyzed patients, 13.3% of them carried inactivated p53 only, 23.3% had inactivated PTEN only, while 20.0% of patients had inactivated both tumor suppressors. These data suggest that inactivation of PTEN, either alone or in combination with the inactivation of p53, prevalently occurs in NSCLC. Correlation analyses imply that inactivation of either p53 or PTEN is an early event in pathogenesis of NSCLC, while inactivation of both tumor-suppressors contributes to further tumor progression. In addition, correlation analysis of inactivated PTEN and p53 with the degree of genomic instability of each patient (obtained in previous study) disclosed that mutated p53 is associated with high genomic instability while inactivated PTEN was more frequent in patients with low genomic instability confirming important role of p53 in maintaining the stability of the genome. Finally, Kaplan &amp; Meyer survival analyses revealed that patients with inactivated p53 have much worse prognoses. In order to conclude the study of p53 and PTEN inactivation, analyses of hypermetylation of PTEN promoter and LOH of p53 gene are underway. Citation Information: Cancer Res 2009;69(23 Suppl):B55.
THU0185 Smoking does not Influence Response to Anti-TNF Treatment with Adalimumab or Etanercept in Patients with Rheumatoid Arthritis
Authors: C. Krieckaert, I. Visman, M. l’Ami, M. Abbas, M. Nurmohamed
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Smoking is associated with an increased risk of developing rheumatoid arthritis (RA) and with poor treatment outcome in early as well as established RA.[1-3] <h3>Objectives</h3> To investigate the effect of smoking on response to the TNF inhibitors etanercept and adalimumab in patients RA. <h3>Methods</h3> Eight hundred sixty eight patients with RA, consecutively included in a prospective observational cohort were followed for 6 months. Patients were treated with either adalimumab or etanercept and drug choice was at the discretion of the treating rheumatologist. Smoking status was recorded at baseline. <h3>Results</h3> Four hundred seventy three patients started with etanercept treatment (55%) and 395 started with adalimumab treatment (44%). In total, 226 patients (31%) were current smokers and smoked a median of 10 cigarettes per day (IQR 6-20), with a median (IQR) of 19.5 (7-31.5) pack years. An additional 296 patients had smoked cigarettes in the past for a median (IQR) of 20 (10-30) years. Baseline DAS28 did not differ between smokers and non-smokers mean (SD) 4.8 (1.3) vs. 5.0 (1.3), respectively (p=0.15). After 4 months of treatment, 33% of patients had achieved minimal disease activity defined as a DAS28&lt;2.6 and this did not differ between smokers and non-smokers (34% vs. 33%, p=0.81). At 6 months of treatment, these results remained the same: 33% for the total patient population, 34% and 33% for smokers and non-smokers, respectively (p=0.74). In addition, pack years was not associated with EULAR response at 4 and 6 months of treatment. <h3>Conclusions</h3> In contrast to previous studies, in our cohort of adalimumab and etanercept treated patients with RA there was no negative effect of smoking on treatment response. <h3>References</h3> Yahya A et al. Mod Rheumatol. 2012 Aug;22(4):524-31. Rojas-Serrano J et al. Clin Rheumatol. 2011 Dec;30(12):1589-93. Söderlin MK et al. Scand J Rheumatol. 2012 Feb;41(1):1-9. <h3>Disclosure of Interest</h3> C. Krieckaert: None Declared, I. Visman: None Declared, M. l'Ami: None Declared, M. Abbas: None Declared, M. Nurmohamed Consultant for: Abbott, Roche, Pfizer, MSD, UCB, SOBI, BMS, Speakers bureau: Abbott, Roche, Pfizer
Abstract 2192: A novel mechanism of EML4-ALK rearrangement in a patient-derived cell line and its tumor growth inhibition by an ALK inhibitor CH5424802.
Authors: Tatsushi Kodama, Noriko Motoi, Hironori Ninomiya, Hiroshi Sakamoto, Kunio Kitada, Toshiyuki Tsukaguchi, Yasuko Sato, Nobuya Ishii, Yasuhito Terui, Kiyohiko Hatake, Yuichi Ishikawa
Journal: Cancer Research (2013)

Abstract Purpose: EML4-ALK is a driver oncogene in non-small cell lung cancer (NSCLC) and has been developed into a promising molecular target for antitumor agents. Although EML4-ALK is reported to be formed by inversion of chromosome 2, other mechanisms of gene fusion remain unknown. Here we characterize the EML4-ALK fusion gene of a new cell line derived from a patient of NSCLC. In addition, the efficacy of ALK inhibitors against this new cell line was examined. Experimental Design: An EML4-ALK-positive cell line, termed LC649, was established from pleomorphic carcinoma, a rare subtype of NSCLC. We investigated the chromosomal aberrations using fluorescence in situ hybridization (FISH) and comparative genomic hybridization (CGH). CH5424802, a selective ALK inhibitor, was evaluated in the antitumor activity against LC649 in vitro and in vivo xenograft model. Results: Our initial characterization revealed that LC649 harbors variant 3 of EML4-ALK fusion with 2-fold copy number gain. Interestingly, CGH and metaphase-FISH analysis showed that LC649 contained, in addition to two normal chromosome 2, two aberrant chromosome 2 that were fragmented and scattered. These observations provided the first evidence that EML4-ALK fusion in LC649 cells was formed in chromosome 2 by a distinct mechanism of genomic rearrangement, termed “chromothripsis”. Additionally, CH5424802 inhibited phospho-ALK and suppressed tumor growth of the LC649 cells in vitro and in vivo in a xenograft model. Conclusions: Our results suggested that chromothripsis may be a mechanism of oncogenic rearrangement of EML4-ALK. CH5424802 was effective against EML4-ALK positive tumors with ALK copy number gain mediated by chromothripsis. Citation Format: Tatsushi Kodama, Noriko Motoi, Hironori Ninomiya, Hiroshi Sakamoto, Kunio Kitada, Toshiyuki Tsukaguchi, Yasuko Sato, Nobuya Ishii, Yasuhito Terui, Kiyohiko Hatake, Yuichi Ishikawa. A novel mechanism of EML4-ALK rearrangement in a patient-derived cell line and its tumor growth inhibition by an ALK inhibitor CH5424802. [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 2192. doi:10.1158/1538-7445.AM2013-2192
AB0613 Omega-3 polyunsaturated fatty acids for the treatment of rheumatoid arthritis: A meta-analysis
Authors: Y.H. Lee, S.J. Choi, J.D. Ji, G.G. Song
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Omega-3 polyunsaturated fatty acids (PUVAs) may lead to a reduction of pain and inflammation via competitively inhibiting the production of PGE<sub>2</sub> and LTB<sub>4</sub> and inhibiting the release of interleukin-1 beta and tumor necrosis factor-alpha. <h3>Objectives</h3> The aim of this study was to assess the effects of omega-3 polyunsaturated fatty acids (PUVAs) (at least 2.7 g) for a minimum duration of 3 months on clinical outcomes in patients with rheumatoid arthritis (RA). <h3>Methods</h3> The authors surveyed randomized controlled trials (RCTs) that examined the effects of omega-3 PUVAs on clinical outcomes in RA patients using Medline, the Cochrane Controlled Trials Register, and by performing manual searches. Meta-analysis of RCT was performed using fixed and random effects models and outcomes are presented as standardized mean differences (SMD). <h3>Results</h3> Ten RCTs involving total of 183 patients and 187 controls were included in this meta-analysis. Meta-analysis showed that omega-3 PUVA had a clear effect versus controls on NSAID consumption (SMD -0.518, 95% CI -0.915 to -0.121, <i>p</i> =0.011), without between-study heterogeneity (I<sup>2</sup> =0%). Patients receiving omega-3 PUVAs fared better than placebo for NSIAD consumption. Although they did not reach statistical significance, tender joint count, swollen joint count, morning stiffness, and physical function was observed to improve in the omega-3 PUVAs group (SMD -0.214, 95% CI -0.489 to 0.062, <i>p</i> =0.128; SMD -0.170, 95% CI -0.454 to 0.114, <i>p</i>=0.241: SMD -0.224, 95% CI -0.955 to 0.212, <i>p</i> =0.221; SMD 0.264, 95% CI -0.232 to 0.724 <i>p</i> =0.314). <h3>Conclusions</h3> This meta-analysis shows that use of omega-3 PUVAs, at dosages of &gt;2.7 g/day, for more than 3 months may be effective in reducing NSAID use in RA patients. Further studies are needed to explore clinical effects including NSAID sparing effect of omega-3 PUVAs in RA. <h3>Disclosure of Interest</h3> None Declared
416 PREDICTION OF ACTIVE HBV-CARRIER STATUS IN A COHORT OF EUROPEAN UNTREATED HBeAg NEGATIVE PATIENTS: A PROSPECTIVE LONGITUDINAL STUDY
Authors: V. Knop, J. Vermehren, H. Wedemeyer, S. Mauss, D. Hueppe, J. Petersen, T. Welzel, A. Buslau, L. Gerber, J. Friess, S. Susser, C. Fueller, S. Zeuzem, C. Sarrazin
Journal: Journal of Hepatology (2013)
Abstract 3723: Predicting breast cancer risk to age 80: A clinical tool
Authors: Graham A. Colditz, Bernard Rosner
Journal: Cancer Research (2011)

Abstract While numerous models of breast cancer risk have been developed, few are used in routine clinical care. Thus women are not advised of potential strategies to reduce their future risk of breast cancer; either SERMS for high risk women or weight control and physical activity, reduction in alcohol or other approaches for moderate risk women. Furthermore, few models incorporate the full range of known risk factors and provide easy access for clinical use. The Rosner-Colditz log incidence model of breast cancer was developed and validated on independent data sets within Nurses’ Health Study cohort 1. The model includes a full range of reproductive and lifestyle risk factors for breast cancer. We now have developed a tool for batch or individual data input that provides 5-year risk, and risk to age 80. Input variables include current age, weigh at age 18, current weight, height, current alcohol intake and at age 18, age at menarche, age at menopause and type of menopause, family history of breast cancer and history of benign breast disease, hormone use (current, past, never) and type of hormone used, duration of postmenopausal hormone use, and age at each birth. Parameter estimates are drawn from Nurses’ Health Study data where we have shown the model performs with higher predictability (area under the ROC curve was 0.623) significantly better than the Gail model (area under the ROC 0.578) (p&amp;lt;0.001). For the total cohort, Incidence of invasive breast cancer in the NHS is consistent with SEER data (O/E = 1.0; 95%CI 0.98-1.03). For clinical use, risk estimates are adjusted for US mortality to provide incidence estimates to age 80 that account for competing risks. Clinical application requires assumptions regarding future weight change, duration of continued use of hormone therapy, and for premenopausal women, future age at menopause. 1. Colditz G, Rosner B. Cumulative risk of breast cancer to age 70 years according to risk factor status: data from the Nurses’ Health Study. Am J Epidemiol. 2000;152(10):950-964. 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 3723. doi:10.1158/1538-7445.AM2011-3723
PMO-245 Infliximab reduces rates of emergency hospital admissions and surgical procedures: a UK retrospective study of Crohn's disease patients
Authors: C D Wheeler, R Chipperfield, T Orchard, J Lindsay
Journal: Gut (2012)

<h3>Introduction</h3> Crohn9s disease affects 50–100 patients per 100 000 in the population and typically follows a progressive course, with an estimated 33% of patients with active disease developing complications requiring hospitalisation or surgery in the first year of diagnosis. Up to 80% of patients require surgery at some point during the course of their disease. This retrospective study assessed the rates of emergency hospitalisation and surgery for a large UK cohort of patients before and after infliximab therapy. <h3>Methods</h3> 18 UK centres participated in the study, including data from a total of 380 individuals with Crohn9s disease who had received their first infusion of infliximab after 1 January 2003. Patients were eligible for inclusion with 12 months data prior to, and 24 months data post infliximab initiation, in their clinical record. Data on all investigations, clinic appointments, admissions and operations were extracted from the patient record in a standardised manner by members of the local clinical team. A prespecified statistical analysis plan compared healthcare resource utilisation at 12, 18 and 24 months after the introduction of infliximab with resource utilisation during the 12 months prior to starting treatment. <h3>Results</h3> In the 12-month period before initiation of infliximab therapy there were a total of 12 emergency admissions for surgical procedures. There were 176 unplanned emergency admissions in the same period to manage complications such as bowel obstruction or flare. In the 24-month period following initiation of infliximab therapy there were significantly fewer cumulative emergency admissions for surgical procedures (8 total, p=0.0184) and management of complications (220 total, p&lt;0.0001). The most common complications resulting in unplanned admissions included abscess, flare and intestinal obstruction which were reduced by half in the first year of infliximab therapy. <h3>Conclusion</h3> In a large UK cohort of Crohn9s disease patients, treatment with infliximab was shown to significantly reduce rates of emergency admissions for either surgical intervention or management of complications. <h3>Competing interests</h3> C Wheeler: Employee of: MSD, R Chipperfield: Employee of: MSD, T Orchard: Grant/Research Support from: MSD, Warner Chilcott, Johnson and Johnson, Consultant for: Warner Chilcott, Ferring, Shire, Speaker bureau with: Warner Chilcott, Ferring, Shire, J Lindsay Grant/Research Support from: MSD, Abbott, Shire, Consultant for: MSD, Abbott, Shire, GSK, Ferring, Warner Chilcott, Atlantic Healthcare, Speaker bureau with: MSD, Abbott, Shire, Ferring, Warner Chilcott.
Large-scale prospective pharmacogenomics study of oxaliplatin-induced neuropathy in colon cancer patients enrolled in the JFMC41-1001-C2 (JOIN Trial)
Authors: M. Kanai, T. Kawaguchi, M. Kotaka, K. Shinozaki, T. Touyama, D. Manaka, K. Ishigure, J. Hasegawa, Y. Munemoto, T. Matsui, A. Takagane, H. Ishikawa, S. Matsumoto, J. Sakamoto, S. Saji, T. Yoshino, A. Ohtsu, T. Watanabe, F. Matsuda
Journal: Annals of Oncology (2016)
Study of Neurobehavioral Symptoms and Impairments in Breast Cancer Patients Receiving Adjuvant Aromatase Inhibitor Therapy.
Authors: J. Weaver, S. Stark, S. Stark, K. Shahverdi, S. Jeter, J. Zorzi, R. Skolasky, Jr, R. Skolasky, Jr, M. Andrejczuk, V. Stearns, B. Gordon, B. Gordon
Journal: Cancer Research (2009)

Abstract Background: Whether treatment with aromatase inhibitors (AI) may be associated with the development of cognitive or other mental impairments is under debate. Few studies have carefully assessed AI-associated changes in cognitive function, and none have assessed differences between the three third-generation AIs – anastrozole, letrozole, and exemestane. We initiated a prospective clinical trial to compare baseline and 1-year change in neurophysiological testing in women initiating adjuvant AI.Patients and Methods: Women with a hormone receptor-positive stage 0-III breast cancer who were about to begin AI treatment were eligible for enrollment. We compared intra-individual neurophysiological testing results at baseline (Session I) and following one year of AI (Session II). Cognitive/behavioral assessment included standardized tests sensitive to 8 neuropsychological domains: General Intelligence, Attention, Perceptual-motor Performance, Working Memory, Visual Long-term Memory, Verbal Long-term Memory, Language, and Executive Functioning. Scoring was based upon age- and education-adjusted normative data. In addition, participants completed several subjective reports of cognitive, physical, and emotional functioning.Results: To date, 53 subjects enrolled in Session I, and 30 completed Session II. Analysis of the 30 women who completed both sessions revealed statistically significant differences (with the significance level set at p=0.05, test-wise), including: impairment from Session I to Session II on the PASAT Trial I (p=0.005) and improvement from Session I to Session II on the following tests: FAS Total (p&amp;lt;0.001); Animal Naming (p=0.025); RAVLT I-V, B, Delay, and Immediate (p&amp;lt;0.001 for all); RAVLT 5-1 (p=0.017); RAVLT % (p=0.022); Logical Memory I (p=0.005) and II (p&amp;lt;0.001); WMS-Faces I &amp; II (p&amp;lt;0.001 for both); WAIS-Picture Completion (p=0.027); and WAIS-Vocabulary (p&amp;lt;0.001).Discussion: Only a few studies have examined the effect of AI treatment on cognitive functioning. Findings from the present study suggest that, following the administration of AI for 1 year, women as a group appear to exhibit impairments in attention (as evidenced by PASAT performance) and possibly in executive functioning. However, there was also improved performance in the areas of language, verbal long-term memory, and visual long-term memory. These preliminary results suggest a need to be sensitive to the possibility that AI treatment may have mixed effects on cognitive and related behavioral functions. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4084.
P187 Treatment of Stable COPD in Alpha 1 Antitrypsin Deficiency (AATD) Patients Using the 2011 GOLD Treatment Algorithm
Authors: A Pillai, RA Stockley
Journal: Thorax (2012)

<h3>Background</h3> Previous versions of the GOLD strategy algorithm recommended treatment based on FEV1 which is now recognised as a poor descriptor of disease impact. The revised 2011 GOLD document has introduced individualised assessment of symptoms and future risk for initial management of stable COPD. Questionnaires such as COPD Assessment Test (CAT) and modified Medical Research Council (mMRC) are suggested to assess symptoms and risk depends on spirometric impairment or exacerbation frequency. <h3>Aim</h3> To apply the current GOLD treatment algorithm to AATD patients and assess their current treatment against that recommended. <h3>Methods</h3> 309 consecutive patients on the AATD registry (PiZZ) were grouped into the four categories (A, B, C, and D) as suggested by GOLD, on the basis of their CAT 10, 13 or mMRC scores and GOLD spirometric stage or Exacerbation frequency. We then documented the treatment combinations being used by the patients in the different groups. <h3>Results</h3> Treatment for patients in the four groups differed widely from GOLD recommendations. Few patients in Group A(CAT10GOLD/MRCGOLD/CAT13GOLD:6%/2%/2% and CAT10EXAC/MRCEXAC/CAT13EXAC:6%/2%/3%) were on the GOLD recommended SABA/SAMA therapy. 40% were on none and 30% were on triple therapy. The majority of patients in group B and Group C (60% and 58% respectively) were on triple therapy with only 10% and 14% respectively being on the recommended regimen. Nearly 70% in group D were on recommended triple therapy with ICS, LABA and LAMA. The proportion of patients in the groups A, B and C assessed by mMRC was significantly different using CAT 10 (p&lt;0.02) but not using CAT 13 (p = not significant). The proportion of patients in group D was similar for all 3 symptom scores (p = not significant). <h3>Conclusions</h3> CAT 13 was most comparable to mMRC for patient distribution. Most of the AATD patients with low risk (low symptoms and high symptoms) were over treated with triple therapy. The majority in the high risk/high symptoms group were appropriately on triple therapy. It remains to be determined how this affects long term outcome.
ACUTE IMPROVEMENT OF VASCULAR FUNCTION AND OXIDATIVE STRESS BY REMOTE ISCHEMIC POST-CONDITIONING IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION
Authors: Ignatios Ikonomidis, Dimitrios Vlastos, Efstathios Iliodromitis, Maria Varoudi, Ioanna Andreadou, George Pavlidis, Leonidas Palaiodimos, George Makavos, Ioannis Paraskevaidis, John Lekakis
Journal: Journal of the American College of Cardiology (2016)
MYOCARDIAL AND END-ORGAN RESPONSE AFTER LONG-TERM MECHANICAL UNLOADING WITH CONTINUOUS-FLOW LEFT VENTRICULAR ASSIST DEVICE: AXIAL- VERSUS CENTRIFUGAL-FLOW
Authors: Mohammad Al-Sarie, Asad Rauf, James Wever-Pinzon, Anna Catino, Josef Stehlik, Abdallah Kfoury, Stephen H. McKellar, Omar Wever Pinzon, Aaron Kelkhoff, Rami Alharethi, Bruce Reid, James Fang, Craig Selzman, Stavros Drakos
Journal: Journal of the American College of Cardiology (2016)