tbuckley/cabot-search huggingface dataset:
OC-082 The Development of a Web-Based System to Enhance Care in Inflammatory Bowel Disease
Authors: C R Calvert, S Lal, C Stansfield, J McLaughlin, A Robinson
Journal: Gut (2013)

<h3>Introduction</h3> Engaging and empowering patients to have greater involvement in their care is central to the vision of many governmental health policies. It is widely recognised that facilitating self-management for patients by providing information to help support understanding, decision-making and motivating behavioural change can lead to significant improved health outcomes.<sup>1</sup> We describe the development of a web-based IBD system that specifically aims to support patients’ in taking a more active role in managing their IBD. <h3>Methods</h3> Design and implementation of a web-based system in the healthcare setting is complex with a number of human, technological and organisational factors that need to be considered from the start of the concept. Stakeholder involvement is essential throughout this process. Using the theoretical framework of self-efficacy we have designed a system with the specific aim to support patients to engage in their health. Our aim has been to develop a web-based system that is easily managed and sustainable for use in routine clinical practise. <h3>Results</h3> ‘My IBD Portal’ has now been implemented. The web-based system is accessed via a secure login and provides patients with a number of components. This includes a summary of their disease, clinic letters and their latest test results. Functions known to further enhance self-management are included with electronic self-monitoring of symptoms and decision support. Secure messaging with the IBD unit is provided. Throughout the site personalised and trusted information links are integrated. The system is automated to populate the specific data fields each day from the hospital electronic medical record. The infrastructure of the system, has been specifically designed to be easily adopted throughout the UK healthcare setting. <h3>Conclusion</h3> Design and implementation of patient-focused ehealth within the NHS is complex. Stakeholder involvement is essential. Evaluation of web-based interventions requires careful consideration, as they are often complex interventions by nature. The revised MRC framework provides a useful resource to develop a systematic process to evaluate such technologies.2 We are currently evaluating the impact of ‘My IBD Portal’ in a formal trial setting. <h3>Disclosure of Interest</h3> None Declared <h3>References</h3> De Silva <i>et al.</i> Evidence:Helping people help themselves. <i>The Health Foundation</i> 2011. http://www.health.org.uk Anderson <i>et al.</i> New MRC guidance on complex interventions. 2008. <i>BMJ;</i><b>338</b>:a1937
The Combination Chemotherapy of Carboplatin and Weekly Paclitaxel Plus Bevacizumab in Patients with Advanced NSCLC
Authors: S. Kitaguchi, M. Kagawa, K. Yamaguchi, M. Watanabe, T. Ogawa, O. Furonaka, F. Sugahara, H. Egawa
Journal: Annals of Oncology (2013)
Incidental Acinic Cell Carcinoma of the Parotid Gland Discordant on 123I-MIBG, 111In-Octreotide, and 18F-FDG PET/CT in a Patient With Neuroendocrine Tumor of the Cecum
Authors: William Makis, Karey McCann, Alexander J.B. McEwan
Journal: Clinical Nuclear Medicine (2015)

A 61-year-old woman diagnosed with a metastatic well-differentiated neuroendocrine tumor of the cecum was referred for radioisotope therapy. Although her metastatic neuroendocrine tumor was positive on both (123)I-MIBG and (111)In-octreotide, there was a left parotid mass that was octreotide avid but MIBG negative. Further investigation also showed discordance on (18)F-FDG PET/CT and excision of the mass revealed an incidental acinic cell carcinoma of the parotid gland. Somatostatin analog imaging and PRRT (peptide receptor radionuclide therapy) may have a role in the management of acinic cell carcinoma.
Counterpoint: Intraperitoneal Chemotherapy: An Investigational Treatment in Ovarian Cancer
Authors: Robert F. Ozols
Journal: Journal of the National Comprehensive Cancer Network (2004)

Intraperitoneal (IP) chemotherapy in ovarian cancer has been studied since 1978. Numerous phase II trials have been performed, which have shown that higher levels can be obtained in the peritoneal cavity compared with systemic circulation after administration of cytoxic agents in a large volume via a semi-permanent catheter. Three randomized trials have been performed in patients with ovarian cancer comparing different IP regimens to standard therapy with intravenous agents. The last two trials from the Gynecologic Oncology Group (GOG) and the Southwest Oncology Group (SWOG) compared two different IP regimens versus standard therapy with intravenous cisplatin plus paclitaxel. Although an improvement in progression-free survival was reported for the IP regimens, they have been associated with unacceptable toxicity, and no IP regimen can be considered standard therapy. Maintenance therapy with IP cisplatin also failed to improve survival in patients who obtained complete remission after intravenous chemotherapy. The GOG is considering another phase III trial of IP therapy that will compare a carboplatin-based regimen versus standard therapy with intravenous paclitaxel plus carboplatin. Unless such a trial shows an improvement in clinical outcome, intravenous carboplatin plus paclitaxel remains the standard of care and IP chemotherapy should not be used outside of a clinical trial.
Pulmonary Epithelial Sodium-Channel Dysfunction and Excess Airway Liquid in Pseudohypoaldosteronism
Authors: Eitan Kerem, Tzvy Bistritzer, Aaron Hanukoglu, Thomas Hofmann, Zhaoqing Zhou, William Bennett, Eithne MacLaughlin, Pierre Barker, Martin Nash, Lynne Quittell, Richard Boucher, Vera Homolya, Bruce Keenan, Michael R. Knowles
Journal: New England Journal of Medicine (1999)

Active sodium absorption is the dominant mechanism of ion transport in airway epithelium, but its role in pulmonary physiology and airway host defense is unknown. To address this question, we studied the function of airway epithelial cells and determined the frequency of pulmonary symptoms in patients with systemic pseudohypoaldosteronism, a salt-losing disorder caused by loss-of-function mutations in the genes for the epithelial sodium channel.
The quest for optimality: A positive heuristic of science?
Authors: Paul J. H. Schoemaker
Journal: Behavioral and Brain Sciences (1991)

Abstract This paper examines the strengths and weaknesses of one of science's most pervasive and flexible metaprinciples; optimality is used to explain utility maximization in economics, least effort principles in physics, entropy in chemistry, and survival of the fittest in biology. Fermat's principle of least time involves both teleological and causal considerations, two distinct modes of explanation resting on poorly understood psychological primitives. The rationality heuristic in economics provides an example from social science of the potential biases arising from the extreme flexibility of optimality considerations, including selective search for confirming vidence, ex post rationalization, and the confusion of prediction with explanation. Commentators are asked to reflect on the extent to which optimality is (1) an organizing principle of nature, (2) a set of relatively unconnected techniques of science, (3) a normative principle for rational choice and social organization, (4) a metaphysical way of looking at the world, or (5) something else still.
Abstract 634: Combinatorial targeting in melanoma cell lines with defined and distinct mechanisms of acquired resistance to V600EB-RAF inhibition
Authors: Hubing Shi, Xiangju Kong, Antoni Ribas, Roger S. Lo
Journal: Cancer Research (2011)

Abstract V600EB-RAF mutation is found in 50-60% of melanomas, and its in-human “druggability” has recently been demonstrated using the novel agent PLX4032, which can achieve an unprecedented ∼80% on-target, anti-melanoma response rate. Acquired resistance to PLX4032, however, has been observed in the majority of patients. We have shown previously that melanoma tumors in patients and cell lines in vitro acquire resistance to PLX4032 not by developing secondary mutations in V600EB-RAF but instead by upregulating PDGFRβ (showing MEK inhibitor insensitivity) or N-RAS (showing MEK inhibitor sensitivity). Here we used distinct subsets of melanoma cell lines (resistance derived in vitro) and short-term cultures (resistance derived in vivo) with hitherto characterized mechanisms of acquired resistance to PLX4032 to define the optimal combination of molecular target inhibition necessary to achieve efficient growth inhibition and cytotoxicity. We focused on a set of molecular targets downstream of overexpressed PDGFRβ or mutant N-RAS in each subset and used specific small molecule inhibitors, singly or in combination, to correlate growth inhibitory responses with p-ERK, p-AKT, p-p70S6K levels and apoptotic responses. We found that single inhibitor treatment led to functionally significant compensatory activation or rebound activities, consistent with dynamic network connectivity at key nodes of signaling. In PDGFRβ-upregulated, PLX4032-resistant melanoma cell lines, combined B-RAF, PI3K and TORC1/2 inhibition led to the strongest synergistic growth inhibitory and cytotoxic responses. In N-RAS-upregulated, PLX4032-resistant cell lines, either MEK or dual TORC1/2 inhibition sufficed to yield significant growth inhibition, and combined MEK and TORC1/2 inhibition did not synergize in growth inhibitory or cytotoxic responses. Together, these observations could serve to rationally guide animal model studies and urgently needed clinical testing in pre-identified subsets of patients relapsing on V600EB-RAF inhibitors. 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 634. doi:10.1158/1538-7445.AM2011-634
Abstract P5-06-15: JNK2 Regulates Mammary Epithelial Cell Differentiation Through Inhibition of p53 and Notch-1 Expression
Authors: M Cantrell, ND Ebelt, CL Van Den Berg
Journal: Cancer Research (2010)

Abstract The classification of patient tumors by clinical subtype has gained great interest due to the implications for prognosis and treatment. For example, it is known that the five-year survival rate of patients diagnosed with the basal subtype of breast cancer is considerably lower than those with luminal subtypes because they lack expression of common drug targets. For this reason, it is important to elucidate the molecular mechanisms responsible for differentiation of mammary stem cell populations into basal and luminal cell lineages. Data presented in this poster outline a novel pathway whereby a ubiquitously expressed protein kinase, JNK2, influences the differentiation of basal, myoepithelial cells (MEps) while suppressing luminal cell (LEp) populations. Gross anatomical observation of whole-mounted mammary glands from wildtype (jnk2wt) and jnk2-/- (jnk2ko) mice revealed that JNK2 increases the rate of pubertal development. Loss of jnk2 increased the rate of ductal invasion, branching, and terminal end bud (TEB) count. Although a slight increase in proliferation was seen in jnk2ko glands, data suggested that it was not due to growth factor signaling. Instead, it was noticed that jnk2ko glands possess 35% fewer MEps (p=0.0078) with a corresponding increase in LEp populations (p=0.100). LEps are known to proliferate at a higher rate than MEps. The differentiation phenotype was corroborated through 3D culture of primarymammary epithelial cells (MECs). The rate of growth of 3D MEC acini was 31.5% higher in jnk2ko cultures than in jnk2wt (P&amp;lt;0.0001). Notch-1, a well-known regulator of MEC difFerentiation, is present in its active form in a greater proportion of cells within jnk2ko TEBs than jnk2wt (p=0.0118, 0.0209). Further, jnk2ko glands were found to possess greater amounts of Notch-1 protein as well as 10.5 times more expression of the Notch target gene, Hes-1 (p=0.005). These results were corroborated with 3D culture of primary MECs as well as in mammary tumor cells. Inhibition of Notch signaling with GSI, in 3D cultures of primary MECs, normalized growth (p=0.8992) and differentiation to jnk2wt control levels. QPCR results showed that jnk2ko glands possess 6.4 times more notch-1 transcript in vivo (P&amp;lt;0.0001). Luciferase assays comparing activity of the notch-1 wildtype promoter to a notch-1 promoter with mutated p53 response elements revealed a dependence of increased notch-1 promoter activity in jnk2ko cells on the p53 response element. QPCR showed 2.78 times more p53 transcript in jnk2ko mammary glands as compared to jnk2wt. These data suggest that JNK2 regulates MEC differentiation through p53 and its target, Notch-1. These findings are significant because they reveal JNK2 as a possible drug target for novel differentiation therapy of basal type breast tumors. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-06-15.
P222 Pleural TB: a common cause of pleural effusion in South London
Authors: O Pickering, R Sarefuji, L Ahmed, R Breen, H Milburn
Journal: Thorax (2013)

<h3>Background</h3> Pleural tuberculosis (TB) is one of the most common forms of extrapulmonary TB, reported to account for up to 25% of TB infected adults, and 30% of exudative pleural effusions in developing countries. Despite this, little information has been reported on its incidence within London. <h3>Aims and methods</h3> A retrospective observational study was performed at a London tertiary referral centre. The aim was to identify the contribution of pleural TB to the overall burden of both pleural and TB disease, and assess diagnostic yields of investigation techniques and outcomes of treatment. <h3>Results</h3> 28 patients were diagnosed with pleural TB between Jan 1<sup>st</sup> 2010- 31<sup>st</sup> Dec 2012. This represented 6.2% of the total number of TB cases, and 4% of the total number of investigated pleural disease cases. The mean age of the patients was 33 ± 10 (range 17–62); 79% were male; 46% were Black African, 29% Asian, 21% Caucasian and 4% Black Caribbean. There was a range of symptoms at presentation, with 96% of patients complaining of at least one symptom (Figure 1). Diagnostic yields were as follows; sputum smear 3% and culture 18%; pleural fluid smear 0 and culture 36%; pleural biopsy smear 11% and culture 54%; pleural biopsy histology 93%. Culture yield for pleural fluid and biopsy was 61%, and overall culture yield for sputum, pleural fluid and biopsy was 68%. All patients’ received quadruple TB therapy, with 82% of patients being given the standard six-month therapy. 92% showed an excellent radiological response, with the x-ray being normal, or with only minor residual abnormalities. To the present date, there has been no diagnosed recurrence of TB. <h3>Conclusions</h3> Pleural TB contributes significantly to the overall burden of pleural disease in this London hospital. TB should be considered in patients presenting with pleural disease, especially young patients from ethnic minority backgrounds. To improve the diagnosis and treatment of pleural TB, culture yields need improvement.
Abstract LB-176: Chemoprevention of NNK-induced lung adenoma and adenocarcinoma in A/J mice by p53 modulating agents, CP-31398 and Prima-1
Authors: Chinthalapally V. Rao, Jagan Mohan R. Patlolla, Li Qian, Yuting Zhang, Misty Brewer, Altaf Mohammed, Dhimant Desai, Shantu Amin, Stan Lightfoot, Levy Kopelovich
Journal: Cancer Research (2012)

Abstract Lung cancer is a leading cause of cancer deaths worldwide. p53 Mutations including wild-type p53 nuclear localization due to excessive endogenous electrophilic molecules are highly prevalent in tobacco associated lung cancers. Here, we report the chemopreventive effects of direct-acting p53 modulating agents, CP-31398 and Prima-1 on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung adenoma and adenocarcinoma in female A/J mice. Seven weeks-old mice on a regular AIN-76A diet, received one dose of 10 μmol NNK /mouse by i.p. injection. Three weeks after NNK treatment, groups of mice (25 mice/group) were fed control AIN-76A or experimental diets containing 50 and 100 ppm CP-31398, or 150 and 300 ppm Prima-1. Mice were sacrificed after 20 weeks (10 mice/group) and/or 36 weeks (15 mice/group) following NNK-treatment and evaluated for lung adenomas and adenocarcinomas by histopathological methods. Administration of 50 and 100 ppm CP-31398 significantly suppressed lung tumor formation by 29% and 39.5% (P&amp;lt;0.01-0.0001), respectively after 20 weeks and 32.2% and 40.1% (P&amp;lt;0.01-0.0001), respectively after 36 weeks. Similarly, 150 and 300 ppm Prima-1 significantly suppressed lung tumor formation by 22.2% and 34% (P&amp;lt;0.04-0.0001) after 20 weeks and 28.8% and 47.4% (P&amp;lt;0.01-0.0001) after 36 weeks, respectively. Inhibition of NNK-induced lung adenocarcinoma by either agent was greater than 55-72% (p&amp;lt;0.0001) after 20 weeks and about 40-57% after 36 weeks. These results suggest that restoring/activating wild-type p53 function by small molecules significantly inhibits NNK-induced lung tumor in A/J mice, most notably delaying progression of adenomas to adenocarcinoma. IHC analysis of lung tumors from NNK-treated mice exposed to either CP-31398 or Prima-1 showed a significantly reduced proliferating cell nuclear antigen (PCNA)-positive index, increased accumulation of nuclear wt-p53 including increased p21 and TUNNEL positive cells compared to lung tumors from NNK-treated mice fed with control diet. Incidentally, neither COX-1 nor iNOS were significantly affected by CP-31398 or Prima -1 in the NNK derived lung tumors. These results demonstrate, for the first time, the chemopreventive role of p53 modulating agents on tobacco specific carcinogen-induced lung adenocarcinomas. {Supported by NIH, NCI grants NO1-CN-53300}. 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-176. doi:1538-7445.AM2012-LB-176
Abstract P176: The Prevalence and Correlates of Advanced Atherosclerosis Among Those With Optimal Low-Density Lipoprotein Cholesterol Levels: The Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Mahmoud S Al Rifai, Ron Blankstein, Seth S Martin, John W McEvoy, Michael J Blaha, Roger Blumenthal, Pamela Ouyang, Khurram Nasir, Joseph Yeboah, Steven J Shea, Joseph F Polak, Michael Miedema
Journal: Circulation (2015)

Introduction: The prevalence of atherosclerosis and relative importance of traditional non-lipid risk factors when low-density lipoprotein cholesterol (LDL-C) is optimal remains unclear. Indeed, so...
CD4+ T cells from patients with acquired thrombotic thrombocytopenic purpura recognize CUB2 domain-derived peptides
Authors: Fabian C. Verbij, Annelies W. Turksma, Femke de Heij, Paul Kaijen, Neubury Lardy, Rob Fijnheer, Nicoletta Sorvillo, Anja ten Brinke, Jan Voorberg
Journal: Blood (2016)
Abstract 4182: A screen for genes that define the strong gender bias nature of hepatocellular carcinoma using a transposon mutagenesis murine model
Authors: Vincent W. Keng, Barbara J. Ryan, Kevin A.T. Silverstein, Aaron Sarver, Danhua Fan, Adam J. Dupuy, Nancy A. Jenkins, Neal G. Copeland, David A. Largaespada
Journal: Cancer Research (2010)

Abstract Introduction: Hepatocellular carcinoma (HCC) is a deadly disease where many of the underlying associated genetic mechanisms remain undiscovered. Although HCC has been relatively rare in the US, the growing number of patients with cirrhosis (due to hepatitis infection and/or obesity-related fatty liver) has accounted for a surge in the incidence of HCC. Using the conditional Sleeping Beauty (SB) transposon somatic insertional mutagenesis system in transgenic mice, a novel unbiased HCC genetic screen was performed to elucidate the important genes responsible for this disease1. Methods: Triple transgenic (containing the conditional SB transposase, transposon mutagenic vector and liver-specific Cre transgenes) and quadruple transgenic (as above plus a conditional dominant negative p53 allele) mice were generated and aged for tumorigenesis1. Results: Using this system combined with a conditional p53-deficient background, we were able to identify many HCC cancer candidate genes. In addition, liver tumor nodules were also isolated from experimental mice without a predisposed genetic background. Liver tumors were prevalent in male experimental mice, mimicking the strong gender bias in the incidence of HCC seen in humans. Liver tumors were isolated from female experimental mice with and without a p53-deficient background, only after a prolonged latency (&amp;gt;432-days). From wild-type female liver tumors, we identified 17 candidate genes including the Pten tumor suppressor gene. From p53-deficient female liver tumors, we identified 6 candidate genes including some genes that are implicated in the miRNA18a pathway. This miRNA pathway has been associated with increased incidence of HCC in female patients. Conclusion: SB system allows for the identification of putative genes involved in HCC development in female mice. Finally, our ultimate goal is that candidate genes will be useful in generating possible therapeutic agents for the treatment of HCC and increase our knowledge in defining the underlying genetic mechanisms associated with the strong gender bias nature of this deadly disease. 1. Keng, V.W., et al. (2009). A conditional transposon-based insertional mutagenesis screen for genes associated with mouse hepatocellular carcinoma. Nat Biotechnol. 27, 264-74. 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 4182.