tbuckley/cabot-search huggingface dataset:
Abstract 2496: Characterization of genes critical for chondro-osseous differentiation, metastasis and osteotropism in Ewing Tumors
Authors: Kristina Hauer, Stefan Burdach, Günther H. Richter
Journal: Cancer Research (2012)

Abstract Ewing Tumors (ET) are highly malignant, mainly localized in bone tissue and are molecularly defined by ews/ets translocations. Metastatic spread in ET is frequent and hematogenous. Microarray analysis revealed BRICHOS domain containing proteins important for chondrogenic differentiation and canonical Wnt antagonist Dickkopf, Xenopus, Homolog of, (DKK) 2 critical for terminal bone development, to be over-expressed in ET. However, none of them seemed directly induced via EWS-FLI1 transcription factor activity. RNA interference of DKK2 expression in ET suppressed in vitro proliferation and decreased the ability for colony formation as well as invasive growth of ET cells, while BRICHOS proteins seemed essential for the maintenance of a precursor state of chondrogenic differentiation. Similarly, local tumor growth and metastasis of ET after DKK2 knock down was significantly decreased in Rag2-/-αC-/- mice. In an orthotopic tumor growth model DKK2 knock down in ET cells resulted in a strongly decreased capacity for invasive growth into bone tissue while RNA interference of BRICHOS proteins surprisingly increased their invasiveness when compared to controls. Microarray analysis after DKK2 knock down and subsequent validation with real-time RT-PCR revealed DKK2-mediated induction of CD44, ICAM1, Matrix Metalloproteinase (MMP) 1, and endochondral bone development important Parathyroid Hormone-like Hormone (PTHRP) in ET. Furthermore, subsequent functional assays demonstrated that invasiveness of ET cells was Matrix Metalloproteinase (MMP) 1 mediated, while knock down of one BRICHOS protein resulted in an increased MMP9 expression, indicating the critical involvement of matrix metalloproteases for the invasive ET growth behavior. Thus, DKK2 and BRICHOS domain containing proteins orchestrate and promote bone invasiveness and metastatic spread of this tumor, and provide significant conceptual progress in understanding both the pathogenesis of invasive bone growth of ET in particular and osteotropism in general. 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 2496. doi:1538-7445.AM2012-2496
Abstract 451: Macrophages are critical for promotion of urethane-induced lung carcinogenesis during early stages
Authors: Rinat Zaynagetdinov, Taylor P. Sherrill, Vasiliy V. Polosukhin, Wei Han, Frank B. McMahon, Linda A. Gleaves, Jamie A. Ausborn, Allyson G. McLoed, Fiona E. Yull, Timothy S. Blackwell
Journal: Cancer Research (2011)

Abstract Among the multiple factors initiating and supporting tumor growth, inflammation plays one of the most important roles. Macrophages, which are the primary immune cells in the lungs, have established roles in tumor growth and metastasis; however, information about the role of macrophages in early carcinogenesis is limited. The purpose of this study was to evaluate the role of macrophages in modulation of tumor formation during different stages of urethane-induced lung carcinogenesis. To assess the role of macrophages in our lung tumor model, we developed a method of non-invasive long-term lung macrophage depletion by repetitive intratracheal injections of liposomal clodronate. Clodronate encapsulated liposomes are well known to cause selective apoptosis of macrophages. Depletion of macrophages during the entire experiment (4 Months) or during the late promotion and progression stages (Months 2-4), when macrophages primarily exhibited a M2 phenotype, significantly reduced tumor vasculogenesis and lung tumor multiplicity. Interestingly, depletion of alveolar macrophages during lung tumor initiation and early promotion stages (Week 1-2), when macrophages were polarized toward an M1 phenotype, caused similar attenuation of tumor vasculogenesis and lung carcinogenesis as observed after depletion of cells during the entire experiment or late promotion/progression stages. Moreover, early macrophage depletion, but not late depletion, significantly reduced formation of atypical adenomatous hyperplasia (AAH) lesions in the lungs. Our results demonstrate that macrophages are critical for promotion of lung carcinogenesis during early stages and suggest that the M1/M2 paradigm may not be an important concept for describing the impact of macrophages on tumor promotion. 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 451. doi:10.1158/1538-7445.AM2011-451
Normal Thymic Uptake of FDG on PET Imaging
Authors: PRATUL M. PATEL, HALUK ALIBAZOGLU, AMJAD ALI, ERNEST FORDHAM, GREGORY LAMONICA
Journal: Clinical Nuclear Medicine (1996)

Assessment and characterization of the thymus by various imaging methods have been extensively described. The authors report increased uptake of 2-(18)Fluoro-2-deoxy-D-glucose (FDG) in the normal thymus gland of patients between the ages of 2 and 13 years. Most of these patients had PET scans for various oncologic conditions and had no clinical problems referable to the thymus gland. This uptake assumes an important role when evaluating mediastinal uptake in whole-body PET scans in pediatric oncology patients to avoid false-positive interpretation.
Recent Trends in Acute Coronary Heart Disease — Mortality, Morbidity, Medical Care, and Risk Factors
Authors: Paul G. McGovern, James S. Pankow, Eyal Shahar, Katherine M. Doliszny, Aaron R. Folsom, Henry Blackburn, Russell V. Luepker
Journal: New England Journal of Medicine (1996)

Mortality from coronary heart disease (CHD) has declined in the United States since the late 1960s. To understand the reasons for the decline during the period from 1985 to 1990, we examined trends in mortality and morbidity due to CHD, medical care, and risk factors for CHD in a large metropolitan population.
Abstract 286: Cucurbitacin B inhibits epithelial-to-mesenchymal transition in breast cancer cells through Snail downregulation.
Authors: Parul Gupta, Sanjay K. Srivastava
Journal: Cancer Research (2013)

Abstract Metastasis is a primary cause of about 90% of cancer related deaths worldwide. It is associated with epithelial to mesenchymal characteristics transition (EMT), which helps in attaining migratory phenotype by tumor cells. Cucurbitacin B (CuB), a triterpenoid steroidal compound has been shown to suppress JAK/STAT3 signaling and cause G2/M arrest in cancer cells. However, the role of CuB as an anti-metastatic agent still remains to be elucidated. In the present study, we investigated the effects of CuB on EMT in breast cancer cells. These cells are known to exhibit significant mesenchymal properties that endow aggressive nature. Our results show that CuB significantly suppressed cell migration of MDA-MB-231 cells in wound healing assay. In addition, we also observed reduced cell invasion with CuB treatment using transwell invasion assay. To elucidate the mechanism of these effects, western blotting was performed using whole cell lysates from CuB treated MDA-MB-231 cells. We observed significantly reduced expression of snail and twist with CuB treatment. Snail and twist are known to be repressors of E-cadherin. Generally upregulation of snail and twist mark the initiation of EMT, and eventually leads to loss of epithelial signature of cells. Furthermore, with CuB treatment upregulation of E-cadherin was observed. Transforming growth factor β is known to induce EMT in malignant breast cancer cells. We further investigated the role of CuB on TGFβ induced EMT. Interestingly, we observed that TGFβ induced snail expression was reversed by CuB in MDA-MB-231 cells. Moreover, CuB treatment also contributed protection to the loss of E-cadherin caused by TGFβ treatment. Taken together our results indicate reversal of EMT by CuB treatment in breast cancer cells, which lead to suppression of metastasic ability. However, further in vitro and in vivo mechanistic studies are under progress. [Supported in part by R01 grant CA129038 (to S.K.S) awarded by the National Cancer Institute]. Citation Format: Parul Gupta, Sanjay K. Srivastava. Cucurbitacin B inhibits epithelial-to-mesenchymal transition in breast cancer cells through Snail downregulation. [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 286. doi:10.1158/1538-7445.AM2013-286
TIME BASED MEASURES OF TREATMENT EFFECT: REASSESSMENT OF TICAGRELOR VERSUS CLOPIDOGREL IN THE PLATO STUDY
Authors: Stefan K. James, Andrea Bellavia, Nicola Orsini, Lars Wallentin, Christopher Cannon, Robert Harrington, Anders Himmelmann, Johan Sundstrom, Henrik Renlund, Per Lytsy
Journal: Journal of the American College of Cardiology (2016)
Abstract 2702: WAVE3 regulates NFκB signaling and sensitizes cancer cells to apoptosis and cell death driven by TNFα.
Authors: Gangarao Davuluri, Khalid Sossey-Alaoui, Edward Plow
Journal: Cancer Research (2013)

Abstract ABSTRACT WAVE3, a member of actin nucleation proteins promotes cancer invasion and metastasis, in part through regulation of expression and activity of key matrix metalloproteinases (MMPs) MMP9, which is centrally involved in invadopodia-mediated degradation of the extracellular matrix (ECM). MMP9 is also a major NFκB target gene, suggesting a potentially important role of WAVE3 in this pathway. Mechanistically, we found that loss of WAVE3 in cancer cells leads to significant inhibition of TNFα-induced NFκB activation as a result of de-stabilization of the IκBα-NFκB complex. Conversely, overexpression of WAVE3 was sufficient to enhance NFκB activity by stabilizing the IκBα-NFκB complex. We used both pharmacological and genetic manipulations of NFκB effector molecules and identified IKKβ but not IKKα as the primary upstream target for WAVE3-mediated regulation of NFκB activity. We also showed that loss of WAVE3 resulted in a significant inhibition of TNFα-mediated MMP9 expression and activity. Loss of WAVE3 also sensitized cancer cells to TNFα-driven apoptosis and cell death. Finally, we showed that either the basic rich (BR) or the proline rich (PR) domain of WAVE3 is sufficient to modulate NFkB signaling. Our results identify a novel function of WAVE3 in NFκB signaling, where its activity is essential for the stabilization of NFκB complex that promotes the metastatic phenotype of cancer cells. Therefore, therapeutic targeting of WAVE3 may prove beneficial for preventing or reducing the metastatic burden in cancer patients. Citation Format: Gangarao Davuluri, Khalid Sossey-Alaoui, Edward Plow. WAVE3 regulates NFκB signaling and sensitizes cancer cells to apoptosis and cell death driven by TNFα. [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 2702. doi:10.1158/1538-7445.AM2013-2702
P15.02 * HEALTH-RELATED QUALITY OF LIFE IN STABLE, LONG-TERM LOW-GRADE GLIOMA SURVIVORS
Authors: F. W. Boele, L. Douw, J. C. Reijneveld, R. Robben, M. J. B. Taphoorn, N. K. Aaronson, J. J. Heimans, M. Klein
Journal: Neuro-Oncology (2014)

BACKGROUND: Low-grade glioma (LGG; WHO grade I or II) patients often experience long periods of stable disease, emphasizing the importance of maintaining an optimal health-related quality of life (HRQOL). In this study we assessed the changes in HRQOL in long-term LGG survivors with stable disease. METHODS: Patients completed self-report measures of generic HRQOL (SF-36) and disease-specific HRQOL (EORTC QLQ-BN20). Assessments took place at mid-term and long-term follow-up, on average 6 and 12 years following histological diagnosis and initial treatment, respectively. Wilcoxon signed-rank tests were used for group-level analysis and meaningful intra-individual changes (i.e. a 95% confidence interval around the standard error of measurement of a scale) were calculated where applicable. RESULTS: Stable LGG patients (N = 65) reported poorer physical health at long-term than at mid-term follow-up, as well as more uncertainty about the future and more weakness in the legs. Meaningful decline in physical health was found in 29% and 26% of patients on the SF-36 PCS and physical functioning scale, respectively. Moreover, 28% of patients experienced more feelings of uncertainty concerning the future (BN20) at long-term follow-up. CONCLUSION: Despite long-term stable disease, subtle impairment in HRQOL can be observed in LGG patients. While in the majority of LGG patients, HRQOL remains mostly preserved, over 26% of patients experience meaningful decline in physical functioning or more feelings of uncertainty concerning the future. For this subgroup, further research into associations between HRQOL and patient-, disease- or treatment-related variables is recommended to better aid them in dealing with the mental and physical consequences of a LGG.
SP0064 Integrated Approaches to Long-Term Condition Management in Primary Care
Authors: C. D. Mallen
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> Coordination of care for patients with long term conditions is becoming increasingly complex. Multimorbidity, the presence of more than one chronic condition, is common in older people and represents one of the major challenges faced by health care practitioners who have to deal with the competing needs and demands of different conditions whilst trying to provide patient centred holistic health care. As a result, clinical care can become fragmented, with patients having multiple appointments, unrealistic treatment schedules and contradictory advice. Chronic musculoskeletal disorders, such as osteoarthritis and chronic low back pain, represent some of the most frequently managed long term conditions in primary care, yet the current disease-orientated organisation of health services can result in these highly disabling conditions being neglected. This presentation will identify the issues faced by clinicians caring for patients with long term conditions in the community, highlighting areas where an integrated approach to managing chronic disease could improve not only patient care but also provide a more cost effective and holistic management strategy. <h3>Disclosure of Interest</h3> None Declared
Transrectal ultrasound-guided endoscopic drainage and vacuum therapy of pelvic abscesses: an alternative to (computed tomography-guided) percutaneous drainage
Authors: J. Knuth, B. Krakamp, M. Heiss, D. Bulian
Journal: Endoscopy (2013)

A 43-year-old, otherwise healthy man had increasing abdominal pain in the lower abdomen without a fever. His leukocyte count was 20.0 × 109/L (normal range: 4 – 9 × 109/L) and the C-reactive protein level was 155.5 mg/L (normal < 5 mg/L). Abdominal computed tomography (CT) confirmed the suspected diagnosis of diverticulitis and revealed a large pelvic abscess ([Fig. 1]). The intended CT-guided drainage [1] carried a high risk of injury to the iliac vessels in a translumbar approach and of damaging the sciatic nerve for access through the obturator foramen. The overlying small bowel forbade a ventral approach. The patient underwent transrectal endosonography ([Fig. 2]) for localization of the abscess. Using an endoscopic cystoenterostomy device (Cystotome, Cook Medical, Winston-Salem, North Carolina, USA), originally developed for transgastric puncturing of pancreatic pseudocysts, the abscess was punctured under ultrasonographic guidance. After the puncture site was emptied of pus and dilated with a standard balloon ([Fig. 3]), the abscess cavity was flushed and a vacuum therapy sponge (Endo-SPONGE, B. Braun, Melsungen, Germany) was inserted into it ([Fig. 4]). The patient received antibiotics and parenteral feed for the first week. No ostomy was placed. The vacuum therapy sponge was changed endoscopically on every third day until day 17, when the patient was discharged. Laparoscopic sigmoid resection was performed 1 month later without complications.
Abstract 4947: microRNA expression in soft tissue sarcomas is associated with prognosis
Authors: Thomas Greither, Peter Würl, Lukasz Grochola, Gareth Bond, Matthias Bache, Matthias Kappler, Christine Lautenschläger, Hans-Jürgen Holzhausen, Alexander Eckert, Helge W. Taubert
Journal: Cancer Research (2011)

Abstract The levels of miR-210 known as hypoxia regulated microRNA were analyzed by quantitative RT-PCR in a cohort of 78 soft tissue sarcomas (STS). The microRNA levels were separated according to the tercentile in low, intermediate and high expression and possible association of microRNA expression and patients’ survival was examined using multivariate Cox's regression hazard analyses. A significant correlation between intermediate miR-210 expression and disease specific death of female STS patients was observed compared to patients with a high expression level in their tumors (RR=11.28; P=0.010). Furthermore, expression of miR-210 was significantly associated with age of tumor onset in a gender-specific manner. Male patients with an intermediate expression of miR-210 showed a 9.6 years later age of tumor onset compared to males with a low expression of miR-210 in their tumors. However, this was not the case for female patients. This study provides the first evidence for a correlation of expression levels of a single microRNA (miR-210) with prognosis and a gender specific association with age of tumor onset for soft tissue sarcoma patients. 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 4947. doi:10.1158/1538-7445.AM2011-4947
Scandal as a Sentinel Event — Recognizing Hidden Cost–Quality Trade-offs
Authors: M Gregg Bloche
Journal: New England Journal of Medicine (2016)

Interview with Dr. Ashish Jha on lessons from the recent Veterans Health Administration crisis and future directions at the VA. (04:55)Download Similar scandals at the Veterans Health Administration and the British National Health Service occurred because performance standards were incompatible with resource constraints, but the gap remained unmentionable amid pressure to make care both better and cheaper.
A gene expression signature predicts chemopreventive response of an EGFR inhibitor in a rat mammary cancer model.
Authors: Y Lu, P Liu, Y Wang, C Grubbs, R Lubet, M You
Journal: Cancer Research (2009)

Abstract Abstract #1111 Rats treated with the carcinogen methylnitrosourea (MNU) develop multiple, hormonally dependent mammary tumors. The efficacy of the epidermal growth factor receptor (EGFR) inhibitor Gefitinib (Iressa) to prevent MNU-induced mammary cancers in female Sprague-Dawley rats was determined. Rats were given a single dose of MNU (75 mg/kg body weight) at 50 days of age. Rats bearing MNU-induced small palpable cancers showed variable responses to treatment with Iressa; with approximately 50% having a complete regression and the remaining 50% having a partial or no response. We conducted exon array studies of differentially expressed genes and/or alternative splicing exons related to the responses (complete vs partial or no response). Preliminary studies showed that, although there were genes whose expression was similarly modulated in both groups, a gene expression signature can be identified that is highly predictive of which rat mammary tumors are susceptible to treatment with Iressa. Cross validation results indicated that gene expression signatures may be useful in predicting the response of a rat mammary tumor to treatment with Iressa. Currently, we are conducting validation studies in a separate set of rat mammary tumors. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1111.
Abstract 2001: Non-negative matrix factorization (NMF) as a clinical classifier: An example with chemotherapy response in ovarian cancer
Authors: Szeto Christopher, Stephen Benz, Charles Vaske, J. Zachary Sanborn, Jing Zhu, Joshua Stuart, David Haussler
Journal: Cancer Research (2010)

Abstract Large-scale whole-genome assays such as aCGH and expression profiling are providing an overabundance of data on disease states, yet much of the information is not relevant to driving the disease. There is a need for generating concise explanatory modules with powerful predictive results. Here we describe a semi-supervised machine-learning method for classifying -omics data with associated clinical features. Using NMF a matrix of -omics data is convoluted step-wise into two matrices; a table of k “metagenes” containing coefficients for membership of each gene, and a table of prediction strengths for each patient into each k-class. Where the class of a patient is known we initially set the prediction strength for that class high, otherwise the prediction strength for each class is set equally. As the NMF algorithm progresses, the class prediction can be swapped if this is supported by the -omics data. Initially the metagene coefficients are unknown and seeded randomly. As NMF does not converge onto a unique solution, multiple metagenes were learned starting at different random coefficients. These multiple models were cross-validated as predictors against held-out sets of patients using a correlation statistic different from the one used to train the model. Where a held-out patient correlates with none of the model's k-classes they are considered members of a novel class, and can be abstained from classification a priori. We applied our method on the TCGA ovarian serous carcinoma. In this study aCGH and expression profiles were was taken before platinum treatment and the time to relapse recorded. These -omics measurements were then integrated into inferred pathway activities using a computational model of the central dogma (DIGMA). We predicted platinum sensitivity (no relapse or relapse after 12 mo) vs. platinum resistance (relapse within 3mo) on these inferred pathway activities. Consistently, the model with the highest predictive accuracy in a cross-validation setting correctly placed patients into the correct class &amp;gt;80% of the time. Using abstaining it is possible to achieve &amp;gt;90% correct prediction upon a subset of the patients. These results provide useful prognostic indicators as well as indicators for which events drive disease. 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 2001.