tbuckley/cabot-search huggingface dataset:
Abstract 2224: EGFR mutation screening in non-small cell lung cancer: Results from 4 German molecular pathology laboratories
Authors: Arndt Hartmann, Robert Stöhr, Andreas Gschwendtner, Eva Geissinger, Stefan Gattenlöhner, Thomas Glück, Petra Rümmele, Wolfgang Dietmaier
Journal: Cancer Research (2011)

Abstract Aims: Somatic mutations in the epidermal growth factor receptor gene (EGFR) have evolved as predictors for sensitivity to EGFR tyrosine kinase inhibitors (TKI) in patients with non-small-cell lung cancer (NSCLC). To date, molecular data underlining the role of EGFR mutations in the tumor as a strong predictor for a better treatment outcome were mostly collected from Asian patients (mutation frequency up to 59.7%). Only one European study (Rosell et al., 2009) verified the predicting power of EGFR mutations in Caucasians living in Europe so far, and reported a notably lower mutation frequency (16.6%) compared to Asian collectives. For Germany, only sparse data are available about the mutation frequency in NSCLC. Here we report the intermediate results from 4 pathology institutes performing quality approved approved EGFR testing certified by the Quality Initiative of the German Society of pathology (QuiP) in non-small cell lung cancer. Material and Methods: Overall, 787 (males: 474, females: 312, n.a.: 1) cases were analysed. The cohort consisted of 782 NSCLC (99.4%) and 5 SCLC (0.6%) selected by attending physicians for EGFR mutation analysis considering TKI treatment. After microdissection, DNA was isolated from serial sections of formalin-fixed, paraffin-embedded tumor tissue after microdissection to obtain at least 70% tumor cells. Exons 18, 19 and 21 of the EGFR gene were analysed using Sanger sequencing. Results: In 72/787 cases (9.2%) an EGFR mutation was detected. Deletions in exon 19 were the most frequent alterations detected (46/72 mutations; 63.9%), followed by point mutations in exon 21 (23/72 mutations; 31.9%). Mutation in exon 18 was a rare event (2/72 mutations; 2.8%). EGFR mutations were significantly associated with adenocarcinomas (p&amp;lt;0.001) (mutation frequency: 11.4%) and female gender (p&amp;lt;0.001). Overall, there was a trend (p=0.052) towards higher age in patients with adenocarcinoma and EGFR mutation compared to cases with EGFR wildtype. This increased age was significantly (p=0.009) associated with an EGFR mutation in female patients. Conclusion: EGFR mutation frequency in this German cohort is lower than reported in Asian or Spanish studies. Mutations in exon 19 were detected more frequently than described in the literature so far. The association with adenocarcinoma histology and female gender could be verified. EGFR mutations seem to be more frequent in patients with higher age. Screening of patients with advanced NSCLC for EGFR mutations is feasible and should be used for improvement of therapy options. 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 2224. doi:10.1158/1538-7445.AM2011-2224
Low dose sequential docetaxel-capecitabine chemotherapy as first-line treatment of metastatic breast cancer (mbc)
Authors: M. Hafeez, A. Shaharyar, A. I. Masood, M. Zikria, A. Usman, K. Shabbir, Z. Nadeem, S. Tahir
Journal: Journal of Clinical Oncology (2008)

12007 Background: The efficacy and toxicity of 100 mg/m2 of docetaxel and 1,250 mg/m2 of capecitabine used either alone or sequentially has been well studied. However, the lower dosage schedule of sequential 75 mg/m2 of docetaxel followed by 1,000 mg/m2 of capecitabine has not been well studied in Asian patients. The objective of this study was to evaluate the efficacy and toxicity of low dose sequential docetaxel-capecitabine chemotherapy as first line treatment of MBC. Methods: Female breast cancers with visceral or visceral and bone metastases and a KPS > 70 were eligible. Adequate marrow, renal and hepatic function was required. Metastatic brain disease and bone as the only site of disease were excluded. Informed consent was obtained from all patients. Docetaxel 75 mg/m2 for four cycles was followed by capecitabine 1,000 mg/m2 b.i.d 14 days for four cycles. Cycles were repeated every 3 weeks. CTCAE version 3.0 of NCI and RECIST was used. Results: From June 2006 to December 2007, 38 patients were enrolled. Median age was 49 years (Range 32–70). With docetaxel treatment, CR was seen in 06 (16%) patients and PR in 20 (53%) with an overall response rate of 69%. Stable disease was seen in 10 (26%) and PD in 02 (05%). Four out of six CRs were in patients with liver metastases. Capecitabine added one CR and six partial responses. Two more patients relapsed during capecitabine treatment. At a median follow up time of one year four patients have died with progressive disease. Significant grade 3 toxicities included neutropenia and diarrhoea in 10 (26%) and 07 (18%) respectively. Febrile neutropenia was seen in 06 (16%). Grade 2 hand-foot syndrome was seen in 16 (42%) patients. Conclusions: This treatment schedule of low dose sequential docetaxel-capecitabine is an effective first line treatment of MBC with good overall response rate and manageable toxicity. No significant financial relationships to disclose.
Drug Interactions and the Prepared Observer
Authors: Kenneth L. Melmon, David W. Nierenberg
Journal: New England Journal of Medicine (1981)

IN this issue of the Journal, Feely and his co-workers convincingly demonstrate an interaction between cimetidine and propranolol that results clinically in a decrease in resting sinus rates beyond what would be expected if either propranolol or cimetidine were given alone. As in other drug interactions, multiple mechanisms appear to contribute to the net effect of cimetidine's interaction with propranolol. Some of these mechanisms may not yet be defined.1 Feely et al. indicate that cimetidine not only lowers liver blood flow, as does propranolol, but independently reduces propranolol's metabolism. Dependent on both liver blood flow and hepatic oxidative pathways, . . .
Molecular alterations in the TCR signaling pathway in patients with aplastic anemia
Authors: Bo Li, Lixing Guo, Yuping Zhang, Yankai Xiao, Mingjuan Wu, Lingling Zhou, Shaohua Chen, Lijian Yang, Xiang Lu, Yangqiu Li
Journal: Journal of Hematology & Oncology (2016)

A previous study has demonstrated a significantly increased CD3ζ gene expression level in aplastic anemia (AA). However, the mechanism underlying the upregulated CD3ζ mRNA expression level and that of T cell activation signaling molecules in AA patients remains unclear. Thus, we investigated the expression levels of the CD3ζ, CD28, CTLA-4, and Cbl-b genes, the SNP rs231775 in the CTLA-4 gene, and the distribution of the CD3ζ 3′-UTR splice variant in AA patients. CD3ζ 3′-UTR splice variants were identified in peripheral blood mononuclear cells (PBMCs) from 48 healthy individuals and 67 patients with AA [37 cases of severe aplastic anemia (SAA) and 30 cases of non-sever aplastic anemia (NSAA)] by RT-PCR. CD3ζ, CD28, CTLA-4, and Cbl-b gene expression was analyzed by real-time quantitative PCR. The SNP rs231775 in CTLA-4 gene was analyzed by PCR-RFLP. CD3ζ and CD28 expression was significantly higher, while CTLA-4 and Cbl-b expression was significantly lower in AA patients compared with healthy individuals. Significantly higher CD3ζ expression was found in the NSAA subgroup compared with the SAA subgroup. 64 % of the AA samples had the same genotype (WT+AS+CD3ζ 3′-UTR); 22 % of the AA patients had a WT+AS−CD3ζ 3′-UTR genotype, and 14 % of the AA patients had a WT−AS+CD3ζ 3′-UTR genotype. The CD3ζ expression level of WT−AS+ subgroup was the highest in the SAA patients. A significantly higher frequency of the GG genotype (mutant type, homozygous) of SNP rs231775 in CTLA-4 gene was found in the AA patients. Positive correlation between the CTLA-4 and Cbl-b gene expression levels was found in healthy individuals with the AA and AG genotypes, but not in the AA patients. This is the first study analyzing the expression characteristics of the CD28, CTLA-4, and Cbl-b genes in AA. Our results suggest that aberrant T cell activation may be related to the first and second signals of T cell activation in AA. The GG genotype of SNP rs231775 in CTLA-4 gene might be associated with AA risk in the Chinese population. The characteristics of CD3ζ 3′-UTR alternative splicing may be an index for evaluating the T cell activation status in AA patients, particularly in SAA patients.
COMPARISON OF UPGRADED VERSUS DE-NOVO CARDIAC RESYNCHRONISATION THERAPY (CRT) DEVICES ON CARDIOVASCULAR OUTCOMES AND RESPONSE: A 5 YEAR REGISTRY
Authors: Christopher James McAloon, Domonic P. Heining, Jethro J. Barker, Benjamin Anderson, Gavin Atherton, Faizel Osman
Journal: Journal of the American College of Cardiology (2015)
TEMPORAL CHANGES IN FRACTIONAL FLOW RESERVE IN INITIALLY DEFERRED VESSELS IN SYMPTOMATIC PATIENTS
Authors: Jason J. Payne, Shiv Kumar Agarwal, Mohan Edupuganti, Naga Venkata Pothineni, Ahmed Almomani, Sabha Bhatti, Barry Uretsky, Abdul Hakeem
Journal: Journal of the American College of Cardiology (2016)
New Insight of Molecular Imaging Into the Atheroma Biology
Authors: Remedios Quirce, Ignacio Banzo, Isabel Martínez-Rodríguez, Julio F. Jiménez-Bonilla, Mariano Rebollo, Adriana Rubio-Vassallo, José M. Carril
Journal: Clinical Nuclear Medicine (2013)

In a 75-year-old patient admitted with a middle cerebral artery stroke, a contrast-enhanced CT showed 3 atheroma plaques. Five days after the stroke, a F-fluoride PET/CT to evaluate calcification and, 24 hours later, a F-FDG PET/CT to evaluate inflammation were carried out. The different metabolic behavior of both radiotracers, showing different intensities and distribution in each plaque, may represent different phases of the atherogenesis and in combination could provide new information for the early identification of the carotid unstable plaque.
Myeloma isotype-switch variants in the murine 5T myeloma model: evidence that myeloma IgM and IgA expressing subclones can originate from the IgG expressing tumour
Authors: MHC Bakkus, K Asosingh, K Vanderkerken, K Thielemans, A Hagemeijer, H De Raeve, B Van Camp
Journal: Leukemia (2001)
AB1186-HPR Compiling and Evaluating Evidence-Based Algorithms for the Monitoring of Rheumatoid Arthritis Patients Receiving Disease Modifying Antirheumatic Drugs and Biological Agents
Authors: J. Vella, L. Grech, B. Coleiro, A. Serracino Inglott, L.M. Azzopardi
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Pharmacological management of rheumatoid arthritis patients is based on the use of complex drugs such as disease modifying anti-rheumatic drugs (DMARDs) and innovative biological agents. Safe use of these drugs involves close and effective monitoring resulting in efficient risk management and improved quality of care provided to patients. <h3>Objectives</h3> The objectives of the study were to compile and evaluate algorithms intended to illustrate a stepwise approach in the monitoring required when prescribing and administering DMARDs and biological agents to rheumatoid arthritis patients. <h3>Methods</h3> A literature review was carried out to assess the current international guidelines on monitoring of DMARDs and biological agents. Interviews were carried out with two consultant rheumatologists as to the practice trends of monitoring. Draft algorithms were compiled and submitted for expert panel review. The expert panel consisting of ten members assessed applicability of the algorithms to the practical scenario, presentation, robustness and validity of the data provided. The final RhMonitoring Algorithms were compiled taking into account feedback proposed by the expert panel. <h3>Results</h3> Algorithms for the 5 most commonly used DMARDs (methotrexate, hydroxychloroquine, sulphasalazine, leflunomide, sodium aurothiomalate) and the locally currently available biological agents, etanercept, adalimumab, infliximab and rituximab were compiled. The expert panel consisted of a consultant rheumatologist, a rheumatology resident trainee, two research and academic pharmacists, a risk management pharmacist, a quality assurance pharmacist, a rheumatology nurse specialist, two medical doctors and a staff nurse. Response rate was 80%. All agreed that the algorithms are easy to follow, well laid out and practical. Three members commented that cautions and contraindications should be included alongside each respective algorithm to highlight these issues. <h3>Conclusions</h3> The developed RhMonitoring Algorithms present in a simplified manner the complex information on the monitoring frequency of DMARDs and biological agents. They also serve to standardise the monitoring plans required with these drugs in order across an interdisciplinary team so as to increase the level of patient care and service development. <h3>Acknowledgements</h3> The research group would like to acknowledge the members of the expert panel. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4880
ASSOCIATION BETWEEN BASELINE LIPOPROTEIN SUBFRACTIONS AND OUTCOMES IN PATIENTS WITH HIGH TRIGLYCERIDE AND LOW HDL-CHOLESTEROL LEVELS: A POST HOC SUBGROUP ANALYSIS OF THE AIM-HIGH TRIAL
Authors: Peter P. Toth, Steven Jones, April Slee, Jerome Fleg, Santica Marcovina, William Boden
Journal: Journal of the American College of Cardiology (2016)
P751 DISTINCT VALUES OF LIVER STIFFNESS PREDICT PROGRESSION TO ADVANCED LIVER FIBROSIS IN HIV-INFECTED PATIENTS WITH CHRONIC HEPATITIS C
Authors: P. Labarga, J.V. Fernandez-Montero, P. Barreiro, M.E. Vispo, R. Sierra, I. Perez, C. de Mendoza, V. Soriano
Journal: Journal of Hepatology (2014)
Central Retinal-Vein Occlusion
Authors: Abtin Shahlaee, Jayanth Sridhar
Journal: New England Journal of Medicine (2015)

A 43-year-old man presented with sudden painless loss of vision in his left eye. Funduscopic examination revealed hyperemia and swelling of the optic nerve, macular edema, diffuse intraretinal hemorrhages, and dilated and tortuous retinal veins.
AB0594 Functional ability and quality of life in patients with rheumatoid arthritis treated with low dose modified-release prednisone in daily practice
Authors: C. Baerwald, F. Buttgereit, J. Währisch, P. Flaxenberg
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Glucocorticoids play a pivotal role in managing rheumatoid arthritis due to their anti-inflammatory and immunosuppressive properties.<sup>1</sup> A clinically relevant reduction of morning stiffness was observed with the modified-release prednisone tablet compared to conventional immediate-release prednisone.<sup>2</sup> <h3>Objectives</h3> This non-interventional study (NIS) investigated the functional ability in patients treated with low-dose prednisone in daily practice. In addition, improvement of Quality of Life was also assessed in terms of daily performance. <h3>Methods</h3> Patients with rheumatoid arthritis (n=2661) were included in this 3-month non-interventional study. This analysis addresses a subgroup of patients treated by general practitioners. Data were recorded at three visits (baseline, at 6 and 12 weeks/study end). The primary endpoint was change of functional ability from baseline utilising the Questionnaire on Activity Status QAS (Numeric Rating Scale: 0 – 100 = severely impaired – completely unimpaired) for 3 parameters (occupational performance, household duties, leisure activities). The second endpoint daily performance was documented using a Visual Analogue Scale VAS (0 – 10 = least daily performance - full daily performance). Laboratory assessments included hematologic and inflammatory markers (C-reactive protein CRP, erythrocyte sedimentation rate ESR). <h3>Results</h3> The subgroup consisted of 928 patients (Ø age 62 years, 70% female) treated with modified-release prednisone. The mean total QAS score of these patients increased markedly from 45.5 to 73.7. The three QAS single dimensions improvement was comparable. Occupational performance increased from 56.7 to 80.5, household duties from 46.8 to 74.0 and leisure activities from 40.4 to 71.0. Median daily performance improved from 5 to 8 on the VAS. Median CRP decreased from 8.3 mg/dl to 5.0 mg/dl and the erythrocyte sedimentation rate decreased from 28 mm/h to 15 mm/h at the end of the NIS. <h3>Conclusions</h3> In this non-interventional study patients treated with modified-release prednisone tablets benefited from better functional ability and Quality of Life being shown under daily practice conditions. These results add to those obtained from previous clinical studies. <h3>References</h3> Buttgereit F et al. EULAR Compendium on Rheumatic Diseases 2009. Buttgereit F et al. Lancet 2008. <h3>Disclosure of Interest</h3> None Declared
Usefulness of ultrasound in small bowel crohn's disease: comparison with magnetic resonance for extension, complications and disease activity
Authors: M. Marino, D. Berretti, F. Toso, Z. Maurizio
Journal: Gut (2011)

<h3>Introduction</h3> In the last years ultrasonography (US) has become an accepted tool in the diagnosis of Crohn9s disease and in the detection of complications. Despite several attempts to correlate ultrasound findings with clinical and biochemical activity, there are as yet no convincing data on the usefulness of US in assessing the activity of CD. The authors studied the role of US in diagnosis, complications detection and disease activity of known small bowel CD comparing the results with MRI. <h3>Methods</h3> In this prospective study the authors compared US with MRI small bowel in a series of patients with known Crohn9s disease who were referred to our centre. US and MRI were performed respectively by one Gastroenterologist experienced on US and a Radiologist dedicated to magnetic resonance enterography who were carried out blindly. All the patients first had an US performed and reported, followed within 7 days by MRI scan. For the purpose of the analysis the authors evaluated the presence of terminal ileitis, small bowel stenosis, fistula, abscess and assessment of disease activity. The latter was matched with lab and clinical parameters. <h3>Results</h3> A total of 46 patients with known CD were identified for this study (aged 16–79 years; mean 40; 33 male). All the patients had an ileo-colonscopy and a conventional enteroclysis in the prior 2 months positive for Crohn9s ileitis. Isolated ileal disease was present in 60% and ileo-colonic disease in the remaining 40%. The results of US compared with the subsequent MR scans showed in diagnosis of terminal ileitis a specificity (Sp) and sensitivity (Sn) respectively of 100% and 96% with a Positive Predictive Value (PPV) of 100% and Negative Predictive Value (NPV) of 87.5%. Also in stenosis detection, US showed Sp 94.4% and Sn 93.3% with PPV and NPV respectively of 93.3% and NPV 94.4%. Good results was also found in detection of complications: for fistula the Sp was 100% and Sn of 85% with a PPV of 100% and NPV of 96% while for abscess Sp was always 100% with a Sn of 25% and PPV and NPV respectively of 100% and 90%. Lower performance of US where found in the assessment of disease activity: Sp of 100% and Sn of 63% with a PPV of 100% but a NPV of 42%. <h3>Conclusion</h3> The results of this study confirm the usefulness of US in CD. The technique is sensitive to localise the affected bowel segments. On the other hand, as previous confirmed from other studies, the sensitivity and the NPV of US in detecting disease activity was low. In this series some limitations in detecting some extraintestinal complications as abscess was also found.
Abstract 3159: Modulating therapeutic targets in B-cell lymphoma: Loss-of-function RNAi screen for CD20 regulators.
Authors: Mikolaj Slabicki, Leopold Sellner, Alexander Jethwa, Michael Boettcher, Thorsten Zenz
Journal: Cancer Research (2013)

Abstract The surface glycoprotein CD20 is expressed on healthy and malignant B-cells and can be therapeutically exploited by monoclonal antibodies (e.g. Rituximab, Ofatumumab, GA-101). Stem cells and pro-B-cells are lacking CD20 surface protein, which allows the reestablishment of B-cell populations after treatment. Other cell lineages do not express CD20. Rituximab has revolutionized clinical practice in the treatment of malignant B-cell lymphoma. However, refractory lymphoma cells can lose the expression of CD20 after Rituximab exposure and B-cell lymphoma with low CD20 surface expression may be less responsive to treatment. Despite the widespread use of CD20 antibodies across lymphoma subtypes, little is known about the endogenous regulation of CD20. It was shown that several chemical compounds may modulate the surface density of CD20 (e.g. histone deacetylase inhibitors), but the regulatory network controlling CD20 levels is not understood. We aim to dissect the CD20 regulatome and to exploit the findings for novel therapeutic strategies. The CD20 regulatome is studied in a Burkitt lymphoma cell line (Raji) characterized by medium expression of CD20 in comparison to other lymphoma models. As a proof of principle, we were able to down-regulate the surface expression of CD20 assayed by FACS with four independent silencing triggers targeting CD20 mRNA. To discover novel regulators of CD20 expression, we performed an unbiased genome-wide RNAi screen. The screen hits are involved in diverse molecular mechanisms such as signaling, trafficking, chromatin remodeling and membrane composition. The group of genes decreasing the expression of CD20 expression can provide an insight into the physiological and pathological machinery involved in CD20 trafficking and processing. The strongest hit in this group, next to CD20 knockdown, is potentially involved in the direct transport of CD20 to the cell surface. Clinically most relevant is the group of genes where silencing increases the expression of CD20. The two strongest hits in this category are a transcription factor and a gene involved in signaling. Detailed molecular characterization of several chosen hits is currently ongoing. Their inhibition may lead to increased sensitivity to anti-CD20 antibodies and thus provide starting points for rational drug design. Citation Format: Mikolaj Slabicki, Leopold Sellner, Alexander Jethwa, Michael Boettcher, Thorsten Zenz. Modulating therapeutic targets in B-cell lymphoma: Loss-of-function RNAi screen for CD20 regulators. [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 3159. doi:10.1158/1538-7445.AM2013-3159
WOMEN SPEAK UP ABOUT HEART HEALTH ACTION: A WOMENS HEART ALLIANCE RESEARCH REPORT
Authors: C. Noel Bairey Merz, Holly Andersen, Mark Keida, Emily Sprague, Mary Walsh, Phyllis Greenberger, Susan Campbell, Irene Pollin, Nancy Brown, Marjorie Jenkins, Rita Redberg, Paula Johnson, British Robinson
Journal: Journal of the American College of Cardiology (2016)