tbuckley/cabot-search huggingface dataset:
Abstract 3986: MicroRNA-155 regulates angiogenesis by targeting Von Hippel-Lindau (VHL) tumor suppressor
Authors: William Kong, Lili He, Lei Tan, Jianping Guo, Domenico Coppola, Marc Coppola, Jin Q. Cheng
Journal: Cancer Research (2011)

Abstract Expression of microRNA-155 (miR-155) is frequently up-regulated in various types of human malignancy, including different forms of B cell lymphoma and carcinoma of breast, lung, colon, head/neck, and kidney; however, its role in cancer angiogenesis remains undefined. In this study, we demonstrate the critical role of miR-155 in regulation of angiogenesis through down-regulation of VHL; in addition we show elevated miR-155 levels in breast cancer correlates to high grade and late stage tumor as well as metastasis and poor overall survival. Stable ectopic expression of miR-155 in human umbilical vein endothelial cells induces tube formation in the absence of VEGF; whereas knockdown of miR-155 inhibits tube formation in the presence of VEGF. Further, we identified VHL as a direct target of miR-155. Stable overexpression of miR-155 results in repression of VHL protein; and knockdown of miR-155 rescues VHL expression. Introduction of VHL cDNA lacking 3’ untranslated region abrogates miR-155 induced tube formation. In addition, evaluation of miR-155 expression in primary breast cancers and normal mammary tissues show miR-155 high in 67 of 154 (43.5%) patients with breast cancer as compared to normal breast tissues. Elevated miR-155 is associated with high grade (49/76, 64.5%) versus low grade (18/78, 23.1%) and late stage (37/70, 52.9%) versus early stage (30/84, 35.7%) as well as invasive (53/85, 62.4%) versus non-invasive (14/69, 20.3%) breast carcinoma. Interestingly, miR-155 is also frequently overexpressed in lymph node-positive tumor (i.e., ≥ 10; 20/32, 62.5%) than node-negative (i.e., &amp;lt; 10; 47/122, 38.2%). Furthermore, patients whose tumors express high levels of miR-155 have shorter overall survival than those of tumors with low levels of miR-155. Our findings indicate that miR-155 plays an important role in tumor angiogenesis by targeting VHL and could be a prognostic marker and a critical therapeutic target in breast cancer. 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 3986. doi:10.1158/1538-7445.AM2011-3986
Abstract 994: Monitoring glucose, glutamine and fatty acid metabolism to determine metabolic vulnerability of tumor cells in vitro
Authors: Lisa Pike, Amy Smift, David Ferrick, Min Wu
Journal: Cancer Research (2011)

Abstract Tumor cells display a metabolism that is strikingly different from that of the normal tissue from which they originated. This metabolic alteration results from activation of oncogenes and/or loss of tumor suppressor genes controlling cellular metabolic pathways as well as adaptation to their microenvironments and provides energy and cellular building blocks, allowing tumor cells to proliferate and survive. The altered metabolism of glucose and glutamine are becoming one of the hallmarks of tumor cells. We present a method that enables rapid assessment of the ability of tumor cells to catabolize the three major nutrient substrates, glucose, glutamine and fatty acids in a microplate using the XF Extracellular Flux Analyzer. Cellular oxygen consumption rate is used as an indicator of substrate oxidation by the mitochondrial respiratory chain upon substrate addition and extracellular acidification rate upon glucose addition is used as an indicator of glycolysis. Furthermore, the maximal capacity of glycolysis and of mitochondrial substrate oxidation is determined by forcing one of the two energy-producing pathways to operate at maximum. In addition, pharmacological inhibition of distinct metabolic pathways allows us to discern the biochemical pathways used, i.e., whether glutamine is metabolized through aminotransferase or glutamate dehydrogenase. Using this approach, we have demonstrated that the nutrient levels in culture medium can markedly shift the ability of cancer cells to use glucose for glycolysis versus oxidation of glutamine and fatty acids and is accompanied by modulation of cell proliferation rate. For example, excessive nutrients induced activation of fatty acid oxidation and enhanced glutamine oxidation in myc-expressing SF188 glioblastoma cells. This shift in substrate use also sensitized these cells to inhibition of fatty acid oxidation. We observed a concomitant increase in the maximal capacity of the mitochondrial respiratory chain with elevated substrate oxidation. In contrast, the apparent glycolysis rate of SF188 cells was much reduced but the glycolytic capacity was retained, which implies these cells have the flexibility to channel glucose to either energy or building block production required for cell mass duplication. We suggest that this type of dynamic analysis provides a rapid means to determine the ability of various types of tumor cells to use glucose, glutamine and fatty acids as well as the maximal capacity of the machineries of glycolysis and substrate oxidation, which may be indicative of metabolic vulnerability and therefore targets of intervention of a particular tumor cell type. 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 994. doi:10.1158/1538-7445.AM2011-994
Chorioretinal Granuloma in Tuberculosis
Authors: Daniel G Ezra, Carlos E Pavesio
Journal: New England Journal of Medicine (2010)

A 17-year-old boy presented to the emergency room with a 48-hour history of deterioration in the vision of his right eye. Visual acuity was measured at 6/24 in the right eye and 6/6 in the left eye. In the right eye, a small subhyaloid hemorrhage and an associated vitreous hemorrhage were noted. During the next month, the preretinal hemorrhage cleared, revealing a vascularized chorioretinal granuloma in the superotemporal quadrant. A serous retinal detachment with marked retinal exudate was evident, indicating that the lesion was active (Panel A). A physical examination showed no other abnormalities, and the patient's history was unremarkable . . .
Abstract LB-154: Loss of PTEN cooperates with activated RAS in melanoma genesis and progression
Authors: Cristina Nogueira, Kwan Hyun Kim, Kim T. Paraiso, Jan-Hermen Dannenberg, Marcus Bosenberg, Lynda Chin, Minjung Kim
Journal: Cancer Research (2010)

Abstract MAPK and AKT pathways are frequently co-activated in melanoma through overexpression of receptor tyrosine kinases, mutations in their signaling surrogates, such as RAS and BRAF, or loss of negative regulators such as PTEN. Since RAS is a known positive upstream regulator of PI3-K, it has been suggested that the loss of PTEN and the activation of RAS are redundant events in melanoma pathogenesis (Tsao et al., 2000). Here, in genetically engineered mouse models of cutaneous melanomas, we addressed the genetic interactions of activated HRAS and PTEN inactivation in melanoma genesis and progression in vivo. We showed that loss of Pten cooperates with HRAS activation in Ink4a/Arf−/− background and increased penetrance of melanoma development and emergence of metastasis. Correspondingly, Pten loss increases invasion and migration of melanoma cells and non-transformed melanocytes, which correlates with E-cadherin down-regulation. Together, this study demonstrates a synergistic interaction between Pten inactivation and RAS activation in melanoma development and progression. 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-154.
Abstract B32: DNA demethylation and inhibition of HDAC1 and HDAC2 and is sufficient to reactivate epigenetically silenced tumor suppressor genes
Authors: Ernst Geutjes, Rene Bernards
Journal: Clinical Cancer Research (2010)

Abstract Loss of tumor suppressor gene (TSG) function contributes heavily to both the initiation and progression of cancer and can be the result of mutations in the DNA sequence, but can also be caused by epigenetic disruptions. In contrast to somatic mutations of tumor suppressor genes, epigenetic alterations are essentially reversible. Promoter hypermethylation and histone hypoacetylation play a key role in epigenetic silencing of TSGs. Indeed, the DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine (DAC) and the broad spectrum histone deactelyase (HDAC) inhibitor vorinostat are promising anti-cancer drugs. HDAC inhibitors and DAC are currently explored as combination therapy as they synergistically reactivate epigenetically silenced TSGs and may thus have enhanced therapeutic responses when combined. Although pan-HDAC inhibitors have clear anti-tumor activity in the clinic they induce side effects. In addition, as low expression of some HDACs has been associated with cancer development, their further inhibition may actually contribute to tumor progression. Thus, there is great interest to develop selective HDAC inhibitors. However, it is currently unclear which HDAC(s) to hit. We thus screened a HDAC siRNA library for their ability to synergize with DAC in reactivation of silenced TSGs. We found that only HDAC1 knockdown synergized with DAC treatment in the re-expression of epigenetically silenced TSGs. Additional knockdown of HDAC2 dramatically enhanced this effect, suggesting that both HDAC1 and HDAC2 are involved in the silencing of TSGs. We found that the HDAC inhibitor MS-275, which only targets HDAC1-3, was also able to synergize with DAC in reactivation of silenced TSGs which confirms our finding that HDAC1&amp;2 are essential for epigenetic silencing of TSGs. Treatment of cancer cells with DAC and MS-275 resulted in caspase activation which correlated with reactivation of silenced TSGs. We found a strong synergy with DAC and MS-275 in induction of caspase activity and mitochrondrial membrane permeabilization. Collectively, these data show that DNA demethylation and inhibition of HDAC1&amp;2 is sufficient to reactivate silenced TSGs. In addition, these studies suggest that compounds that inhibit HDAC1&amp;2 might be as effective as pan-HDACi as anti-cancer drugs. Citation Information: Clin Cancer Res 2010;16(7 Suppl):B32
The Neglected Dimension of Global Security — A Framework for Countering Infectious-Disease Crises
Authors: Peter Sands, Carmen Mundaca-Shah, Victor J. Dzau
Journal: New England Journal of Medicine (2016)

The Ebola epidemic demonstrated how ill-prepared the global community is for major infectious disease crises. Now an international expert group has outlined a framework for preparedness, detection, and response to future infectious-disease threats.
THU0224 Prevalence of antibodies against ferritin peptides: Epitope mapping of human ferritin heavy chain in GCA and PMR
Authors: N.T. Baerlecken, K. Große, R.E. Schmidt, T. Witte
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> In a previous study, we investigated the prevalence of autoantibodies against the human ferritin heavy chain protein (HFC) in sera of patients with giant cell arteritis (GCA) and/or polymyalgia rheumatica (PMR) (1). Their sensitivity was 92% in untreated, but only 15% in treated and inactive patients. <h3>Objectives</h3> To optimize this potential diagnostic test of GCA/PMR by an epitope mapping of HFC. <h3>Methods</h3> Six ELISAs with six different peptides of HFC as an antigen were established. As autoantigen we used the full recombinant HFC expressed by E. coli or one of six different peptides of the HFC: 1-18Aa MTTASTSQVRQNYHQDSE (purity 98.8%), 19-45Aa AAINRQINLELYASYVYLSMSYYFDRD (purity 98.8%), 52-78Aa FAKYFLHQSHEEREHAEKLMKLQNQRG purity 98.3%), 79-104Aa GRIFLQDIKKPDCDDWESGLNAMECA (purity 98.8%), 105-143Aa LHLEKNVNQSLLELHKLATDKNDPHLCDFIETHYLNEQVK (purity 98.4%), 145-183Aa AIKELGDHVTNLRKMGAPESGLAEYLFDKHTLGDSDNES (purity 98.5%). 70 GCA/PMR sera were tested consisting of 25 patients positive for HFC autoantibodies and 45 patients negative for HFC autoantibodies. 49 sera of fever patients, 31 sera of patients with late onset rheumatoid arthritis and blood donors' sera served as controls. <h3>Results</h3> By combining different ELISAs for autoantibodies against 19-45Aa, 79-104Aa and 105-143Aa, we were able to increase the frequency for all large vessel vasculitis diseases from 25/70 (34%) in previous antibody negative sera to 46/70 (66%) (p&lt;0.0001) without decreasing severly false positive rate of the diagnostic test. The frequency increased from 53% to 74% in GCA and PMR patients with disease flare, from 29% to 40% in GCA and PMR patients in partial remission and from 8% to 45% in GCA and PMR patients in complete remission. <h3>Conclusions</h3> Autoantibodies against different peptides of HFC are valuable markers for early diagnosis for GCA and PMR and may even be useful for verification of the diagnosis after 3 years of treatment. <h3>References</h3> Baerlecken NT, Linnemann A, Gross WL, Moosig F, Vazquez-Rodriguez TR, Gonzalez-Gay MA, Martin J, Kötter I, Henes JC, Melchers I, Vaith P, Schmidt RE, Witte T. Association of ferritin autoantibodies with giant cell arteritis/polymyalgia rheumatica. Ann Rheum Dis. 2012 Jan 5. [Epub ahead of print] <h3>Disclosure of Interest</h3> None Declared
Chemoimmunotherapy with methotrexate, cytarabine, thiotepa, and rituximab (MATRix regimen) in patients with primary CNS lymphoma: results of the first randomisation of the International Extranodal Lymphoma Study Group-32 (IELSG32) phase 2 trial
Authors: Andrés J M Ferreri, Kate Cwynarski, Elisa Pulczynski, Maurilio Ponzoni, Martina Deckert, Letterio S Politi, Valter Torri, Christopher P Fox, Paul La Rosée, Elisabeth Schorb, Achille Ambrosetti, Alexander Roth, Claire Hemmaway, Angela Ferrari, Kim M Linton, Roberta Rudà, Mascha Binder, Tobias Pukrop, Monica Balzarotti, Alberto Fabbri, Peter Johnson, Jette Sønderskov Gørløv, Georg Hess, Jens Panse, Francesco Pisani, Alessandra Tucci, Stephan Stilgenbauer, Bernd Hertenstein, Ulrich Keller, Stefan W Krause, Alessandro Levis, Hans J Schmoll, Franco Cavalli, Jürgen Finke, Michele Reni, Emanuele Zucca, Gerald Illerhaus
Journal: The Lancet Haematology (2016)
Epidémiologie et aspects endoscopiques des adénomes festonnés coliques. Etude rétrospective comparative avec les adénomes classiques
Authors: A Thibault, C Pignodel, S Bastide, P Pouderoux
Journal: Endoscopy (2013)

Le potentiel dégénératif des adénomes festonnés (AF) est de découverte récente. Leur histoire naturelle, leur épidémiologie, les facteurs de risque et les aspects endoscopiques sont encore mal connus. Le but de cette étude était d'étudier les caractéristiques épidémiologiques et endoscopiques des patients atteints d'adénomes festonnés comparativement à ceux porteurs d'adénomes classiques.
Introducing NEJM Knowledge+ and Its Adaptive Personalized Learning
Authors: Graham T. McMahon, Jeffrey M. Drazen
Journal: New England Journal of Medicine (2014)

Even though we both work with medical information all the time in our roles at the Journal, we often find it hard to keep up with new developments in medicine and to ensure that our general medical knowledge is up to speed. We believe everyone in medicine faces the same challenge: figuring out both how to keep up with material that is relevant and important (especially when it's peripheral to our core practice) and how to apply that information to decisions we make with our patients. Research has shown that clinicians learn best when we solve clinical problems that mirror . . .
Abstract 702: RON receptor tyrosine kinase: A potential therapeutic target in malignant pleural mesothelioma
Authors: Steven G. Gray, David Easty, Daisuke Nonaka, Alex Soltermann, Bruno Murer, M John Kennedy, Dearbhaile M. O'Donnell, Lucciano Mutti, Harvey I. Pass, Kenneth J. O'Byrne
Journal: Cancer Research (2010)

Abstract BACKGROUND: Expression of receptor tyrosine kinases (RTK) and their cognate ligands has been described in mesothelioma, leading to the hypothesis that autocrine growth pathways could be therapeutic targets of tyrosine kinase inhibitors (TKIs). METHODS: Phospho-RTK arrays were used to evaluate phosphorylation of 42 RTKs in 4 mesothelioma cell lines and 11 mesothelioma surgical specimens. Western Blot analysis, IHC, cellular migration and invasion assays were performed. RESULTS: Tumours contained 14 phospho-RTKs. RON emerged as a frequently identifed kinase which has not been previously reported in mesothelioma. An extended panel of sixteen mesothelioma tumour and five benign pleural tissue samples were characterised by western blot analysis. The presence of RON message was confirmed by RT-PCR with specific primers in mesothelioma cell lines Western blot analysis detected RON in 16 tumours and 4 cell lines but not in the SV-40 transformed normal mesothelial MET-5A cells. Mesothelioma expressed different isoforms of RON compared to benign pleural plaques: both benign pleural plaques and mesotheliomas expressed the shortform of RON (sf-RON), whereas, the larger RON variants, Δ160 and Δ165, were seen in mesothelioma samples. IHC was subsequently carried out on a large series of FFPE samples (n&amp;gt;400), with clinical followup to determine if RON expression correlates with prognosis or response to therapy. Scratch assays using antibodies directed against RON prevented MPM cell line migration CONCLUSIONS: Mesothelioma contains multiple activated RTKs including RON. Previously, RON was shown to mediate epithelial mesenchymal transition (EMT). This may be significant given the epithelioid to sarcomatoid spectrum of mesothelioma. Expression of Δ160 and Δ165 was previously reported in gastric and colorectal cancers and may be associated with oncogenesis. RON has been identified as a therapeutic target in pancreatic cancer and this may also apply in mesothelioma. Functional studies on targeting RON in mesothelioma are ongoing. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 702.
A Controlled Trial of Plasmapheresis Therapy in Severe Lupus Nephritis
Authors: Edmund J. Lewis, Lawrence G. Hunsicker, Shu-Ping Lan, Richard D. Rohde, John M. Lachin
Journal: New England Journal of Medicine (1992)

The prognosis of patients with systemic lupus erythematosus who have glomerulonephritis is poor, despite treatment with immunosuppressive therapy. Plasmapheresis therapy has been used, but there have been few controlled clinical observations of its efficacy.
Commentary: Expanded Operational Concept of High Risk Groups and Its Role in Standard Setting
Authors: Edward J. Calabrese
Journal: Environmental Health Perspectives (1983)

The role of the knowledge of high risk groups in the standard-setting process is examined.The overall conclusion is that many potential high risk segments of the population have not been studied adequately and that this deficiency in our knowledge markedly reduces the ability of decision makers to derive appropriate regulatory deci- sions by either ignoring the potential health effects or applying potentially excessive and expensive safety factors.
Resolution of a refractory severe biliary stricture using a diathermic sheath
Authors: H. Kawakami, M. Kuwatani, K. Eto, T. Kudo, Y. Abe, S. Kawahata, M. Kato
Journal: Endoscopy (2012)

Endoscopic treatment of postoperative bile duct strictures (BDSs) is safe and effective [1]. However, when the BDS is severe and only the guide wire can be passed through it, stent placement is not possible. We describe a case of refractory, severe postoperative hilar BDS that was successfully treated using a diathermic sheath.
Pulmonary Epithelial Permeability in Hyaline-Membrane Disease
Authors: Ann L. Jefferies, Geoffrey Coates, Hugh O'Brodovich
Journal: New England Journal of Medicine (1984)

Neonatal hyaline-membrane disease is complicated by pulmonary edema, yet left atrial pressures are normal. Alveolar-capillary-membrane permeability may therefore be increased. To assess pulmonary epithelial permeability, we measured the pulmonary clearance and half-life of aerosolized 99mTc-diethylenetriamine pentacetate (99mTc-DTPA) on 31 occasions in 15 intubated premature infants with hyaline-membrane disease. Three infants with respiratory failure due to other diseases were studied on four occasions. All studies of infants with hyaline-membrane disease that were performed in the first 72 hours of life demonstrated a biphasic clearance curve with a rapid-phase half-life of 1.6±0.6 minutes (mean ±S.D.). As these infants recovered, the curve became monophasic with a half-life of 56.0±32.1 minutes. Two infants remained dependent on oxygen and ventilator support and had persistent biphasic curves with a rapid-phase half-life of 1.5±0.7 minutes. All infants without hyaline-membrane disease had monophasic curves with a half-life of 65.4±33.6 minutes. Using a similar technique, we observed that newborn lambs and piglets have a monophasic pulmonary clearance of 99mTc-DTPA (114±59 minutes in lambs and 52.5±16.3 minutes in piglets). We conclude that the lungs of neonates with hyaline-membrane disease are abnormally permeable to small solutes and that this abnormality persists in infants with subsequent chronic lung disease. (N Engl J Med 1984; 311:1075–80.)