tbuckley/cabot-search huggingface dataset:
Abstract 3515: Combined effects of leptomycin B and doxorubicin on lung cancer
Authors: Chuanwen Lu, Everardo Cobos, Weimin Gao
Journal: Cancer Research (2011)

Abstract To develop novel molecularly targeted therapy has become an important focus of research efforts in lung cancer treatment. Our previous study has shown leptomycin B (LMB), by blocking chromosome maintenance region 1 (CRM1), significantly inhibits cell proliferation in lung cancer cells in a p53-dependent manner. These results suggest the potential use of LMB as a new therapeutic regimen for lung cancer treatment. On the other hand, doxorubicin (DOX) is one of the most effective anticancer agents, which induces p53 activation and nuclear accumulation. The objective of this study is to determine the combinative cytotoxic and molecular effects of LMB and DOX on lung adenocarcinoma cell line, A549. Cells were treated with DOX alone, pre-treatment of DOX/LMB and subsequent treatment of LMB/DOX, or DOX and LMB simultaneously. Cell viability was measured by the MTT assay. The inhibitory effects of DOX on A549 were dose and time-dependent (P&amp;lt;0.001). The 50% inhibitory concentrations (IC50s) of DOX at 24, 48, and 72 h were 60.0, 2.2, and 1.7 µM, respectively. The pre-treatment of 0.5 µM DOX for 24 h significantly improved the cytotoxic effects of LMB on A549 cells at 48 h (P&amp;lt;0.05). The resulting IC50 of LMB was decreased more than 2 fold after pre-treatment of DOX (4.4 nM) as compared to that of LMB alone (10.6 nM). However, the pre-treatment of LMB and the simultaneous treatment of DOX and LMB did not change the cytotoxic effects of either treatment of LMB or DOX. p21 and survivin are well-known p53 downstream genes that play important roles in cell cycle arrest and/or apoptosis. The protein expression levels of these two genes were further analyzed by western blots. Our results showed that the protein expression level of p21 was significantly increased while the protein expression level of survivin was significantly decreased in A549 cells treated with either pre-treatment of DOX and LMB or LMB alone in comparison with those of controls. Furthermore, these changes were more pronounced in pre-treatment of DOX and LMB group as compared to those of LMB alone group. Taken together, our data suggest that the combined therapy using an initial DOX treatment (through activating p53) and subsequent LMB treatment (through blocking the CRM1 function to accumulate activated p53 in the cellular nucleus), that lead to the activation of p53 downstream transcripted genes for cell cycle arrest and apoptosis, might be more effective as a new therapeutic strategy for lung cancer treatment. 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 3515. doi:10.1158/1538-7445.AM2011-3515
Rapid Delivery of Multiple High-Dose Chemotherapy Courses With Granulocyte Colony-Stimulating Factor and Peripheral Blood-Derived Hematopoietic Progenitor Cells
Authors: JOHN CROWN, CAROLYN WASSHERHEIT, THOMAS HAKES, DAVID FENNELLY, LILIAN REICH, MICHAEL MOORE, JEFFREY SCHNEIDER, JOHN CURTIN, STEPHEN C. RUBIN, BONNIE REICHMAN, MALCOLM MOORE, T. J. YAO, THERESA GILEWSKI, SUBHASH GULATI, MAURIE MARKMAN, LARRY NORTON
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article Rapid Delivery of Multiple High-Dose Chemotherapy Courses With Granulocyte Colony-Stimulating Factor and Peripheral Blood-Derived Hematopoietic Progenitor Cells Get access JOHN CROWN, JOHN CROWN Search for other works by this author on: Oxford Academic PubMed Google Scholar CAROLYN WASSHERHEIT, CAROLYN WASSHERHEIT Search for other works by this author on: Oxford Academic PubMed Google Scholar THOMAS HAKES, THOMAS HAKES Search for other works by this author on: Oxford Academic PubMed Google Scholar DAVID FENNELLY, DAVID FENNELLY Search for other works by this author on: Oxford Academic PubMed Google Scholar LILIAN REICH, LILIAN REICH Search for other works by this author on: Oxford Academic PubMed Google Scholar MICHAEL MOORE, MICHAEL MOORE Search for other works by this author on: Oxford Academic PubMed Google Scholar JEFFREY SCHNEIDER, JEFFREY SCHNEIDER Search for other works by this author on: Oxford Academic PubMed Google Scholar JOHN CURTIN, JOHN CURTIN Search for other works by this author on: Oxford Academic PubMed Google Scholar STEPHEN C. RUBIN, STEPHEN C. RUBIN Search for other works by this author on: Oxford Academic PubMed Google Scholar BONNIE REICHMAN, BONNIE REICHMAN Search for other works by this author on: Oxford Academic PubMed Google Scholar ... Show more MALCOLM MOORE, MALCOLM MOORE Search for other works by this author on: Oxford Academic PubMed Google Scholar T. J. YAO, T. J. YAO Search for other works by this author on: Oxford Academic PubMed Google Scholar THERESA GILEWSKI, THERESA GILEWSKI Search for other works by this author on: Oxford Academic PubMed Google Scholar SUBHASH GULATI, SUBHASH GULATI Search for other works by this author on: Oxford Academic PubMed Google Scholar MAURIE MARKMAN, MAURIE MARKMAN Search for other works by this author on: Oxford Academic PubMed Google Scholar LARRY NORTON LARRY NORTON Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 24, 16 December 1992, Pages 1935–1936, https://doi.org/10.1093/jnci/84.24.1935 Published: 16 December 1992
Abstract 366: Downregulation of THBS1 is a critical step in glioblastoma angiogenesis.
Authors: Michael D. Brooks, Erin Jackson, David Piwnica-Worms, Robi D. Mitra, Joshua B. Rubin
Journal: Cancer Research (2013)

Abstract One of the hallmarks of Glioblastoma multiforme (GBM) is its abundant vasculature. These blood vessels support the tumor in a number of ways, including providing a niche for glioblastoma cancer stem cells. GBM tumors drive the formation of their vasculature and associated germinal niches through reciprocal inductive interactions between GBM cells and endothelial cells. Targeting the primary drivers of angiogenesis, VEGF and bFGF, in anti-angiogenic cancer treatments has value but is not curative. We hypothesize that identification of additional angiogenic molecules and pathways will provide new avenues for treatment. We used microarrays to perform global gene expression profiling to identify genes that are increased or decreased in expression as a consequence of functional interactions between GBM and brain microvascular endothelial cells. We identified several regulators of angiogenesis whose expression is modulated by this cell-cell interaction, but were particularly interested in the downregulation of Thrombospondin-1 (THBS1) and its associated receptors. THBS1 is a powerful anti-angiogenic protein and has previously been implicated in cancer, but its precise mechanism in glioblastoma angiogenesis is not yet known. A number of in-vitro experiments validated the importance of THBS1 in the interaction between GBM and endothelial cells. In-vivo mouse xenograft experiments showed that overexpression of THBS1 strongly inhibited tumor formation. We believe these results reveal the importance of factors other than VEGF in glioblastoma angiogenesis and provide a rationale to evaluate combinatorial targeted anti-angiogenic therapy for GBM. Citation Format: Michael D. Brooks, Erin Jackson, David Piwnica-Worms, Robi D. Mitra, Joshua B. Rubin. Downregulation of THBS1 is a critical step in glioblastoma angiogenesis. [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 366. doi:10.1158/1538-7445.AM2013-366
Soundings: In captivity—at Lewes
Authors: George Dunea
Journal: BMJ (2004)

The life of Dr Juhan Paasikivi has been closely linked to Finland's struggle for independence. His grandfather was Finland's prime minister and president in the perilous times following the second world war. His father was killed in the Russo-Finnish winter war of 1939. He became an academic physician in Stockholm and in the 1960s showed that tolbutamide lowered the incidence of myocardial infarctions in patients with abnormal glucose tolerance.

He had a country house in the Aland Islands, where during the Crimean war an Anglo-French naval expedition under Sir Charles Napier stormed the fortress of Bomarsund (few casualties, but 600 died later from cholera). They took Finnish prisoners (regarded at the time as “Russian”), who were then stranded for six weeks on the battleship St Vincent and later the Devonshire—without much food but on hammocks infested with lice, allegedly left over by the French.

In October 1854 some 170 emaciated “poor victims of the ambition and criminalty of the emperor of Russia”—including 15 officers, six wives, and one child—were marched to a former jail in the “ordinarily quiet country town” of Lewes, England. Treated on the whole quite well, even taken once a week to the town's outskirts to breathe the fresh air, they were housed three in a room with no doors or fireplaces, kept on frugal rations of beef and cocoa, but weighed periodically to ensure they were getting enough food.

Several tried to escape and were recaptured; two escaped in civilian clothes with false beards, almost walked into the British embassy in Hamburg, but eventually made their way to St Petersburg. In November 1855 a “young Fin” was unexpectedly born to one of the wives and duly baptised. Altogether some 27 prisoners died—from “rheumatism and disease of the chest,” “dysentery with ague and fever,” “phthisis pulmonalis,” and “extensive disease of the left orbit.” Some of the officers were “in great favour with the young ladies,” but thought that the English danced the waltz rather poorly.

All this is detailed in a large file of letters and newsletter clippings from the 1854-5 Illustrated London News and the Sussex Advertiser that Dr Paasikivi sent to me some 25 years ago. For many years we planned to meet in person. It never came to be. He died in October 2004, age 74.
OP0285 Assessment of Patient Needs to Design a Patient Education Program in Systemic Lupus Erythematosus
Authors: H. Devilliers, B. Hervier, M. Antignac, Z. Amoura
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Systemic Lupus Erythematosus is a chronic autoimmune disease. To prevent short-term and long-term burden of the disease, health education is an essential complement to drug therapy. <h3>Objectives</h3> The aim of this study was to collect information to design a patient education program (PEP) for patients with systemic lupus erythematosus (SLE), based as much as possible on their expectations. <h3>Methods</h3> Three different approaches were used for consulting patients: 1. A questionnaire on their expectations in terms of a PEP was sent to the members of SLE associations and offered to patients at the French reference center for SLE. 2. A focus group was conducted and 3. After the teaching sessions, satisfaction questionnaires were also evaluated. <h3>Results</h3> The patients who answered the expectations questionnaire (n=422, women/men sex ratio = 12.6) showed interest in the PEP in great numbers (70.4%). Their expectations were broad, and covered the topics of pregnancy (90% of the women under age 40), the evolution of the disease (80.8%), the respective roles of the different treatments (70.4%) and also the management of everyday symptoms: fatigue and pain (66.4%). The focus group (8 people) highlighted the need for improving how the diagnosis of the disease was delivered, and also revealed the loneliness and the guilt experienced by some patients toward their relatives. Satisfaction questionnaires confirmed these expectations for the PEP, and even extended them to new topics: the mechanism behind SLE, travel and leisure, and possible accommodations in the workplace. <h3>Conclusions</h3> the direct consultation of patients with SLE targeted by a PEP program specific to systemic lupus allowed us to confirm and adapt the topics and the content of a program designed by medical staff. <h3>Disclosure of Interest</h3> None Declared
Abstract 1057: BRMS1 restoration of gap junctional intercellular communication involves modulation of KATP channels and downregulation of phosphoinositide 3-kinase (PI3K)
Authors: Thomas M. Bodenstine, Kedar S. Vaidya, Aimen Ismail, Leah M. Cook, Danny R. Welch
Journal: Cancer Research (2010)

Abstract Metastatic disease remains the most lethal aspect of cancer, accounting for over 90% of cancer related mortality. Breast Cancer Metastasis Suppressor 1 (BRMS1) specifically inhibits the ability of tumor cells to metastasize to secondary sites while having little or no affect on primary tumor growth. Clinically, a loss of BRMS1 mRNA expression in breast cancer patients is correlated with poor prognosis and a decrease in BRMS1 protein levels predicts reduced disease free survival. The mechanisms of BRMS1 remain unclear; however expression of BRMS1 significantly decreases the PI3K signaling pathway, a pathway that is often over activated in cancer cells. PI3K is a lipid kinase that phosphorylates phosphatidylinositol (4,5)-bisphosphate (PtdIns(4,5)P2) to PtdIns(3,4,5)P3, leading to downstream signaling. BRMS1 acts to reduce the substrate of PI3K, PtdIns(4,5)P2, by &amp;gt;90% when expressed in metastatic cells. Re-expression of BRMS1 in cancer cell lines also restores gap junctional intercellular communication (GJIC), a process that mediates cellular homeostasis and is often lost during neoplastic progression. GJIC has been shown to be affected by PI3K; thus we hypothesized that inhibition of PI3K signaling by BRMS1 might be responsible for the restoration of GJIC. In support of this, treatment with the PI3K inhibitor LY294002 (10µM) in vector control and parental cell lines from multiple cancer cell types, mimicked the effects of BRMS1 on GJIC. Interestingly, inhibition of signaling molecules further downstream of PI3K (AKT, mTOR) did not produce the same effect, suggesting the mechanism of action may directly involve the ratio of PtdIns(4,5)P2/PtdIns(3,4,5)P3. We show that alterations in an ATP dependent potassium channel, KATP, regulated by phosphoinositides, is responsible for the changes in GJIC observed by BRMS1 expression. Delineation of this mechanism will allow for in vivo analysis to determine if changes in GJIC are causative for the BRMS1 mediated suppression of metastasis. Taken together, our data suggest an inhibitory mechanism on gap junctional communication mediated by PI3K, that is relieved by restoration of BRMS1 expression. 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 1057.
Abstract 86: Inhibition of oncogenic Pim kinases, including Pim-2, alters cell growth and signaling in pancreatic cancer
Authors: Dana M. Austin, Vijaya B. Nandiwada, Carmen M. Baldino, Justin Caserta, Chee S. Lee, Yvonne Flanders, Stephane Dumas, Antonio T. Baines
Journal: Cancer Research (2012)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is the most common cancer of the pancreas, comprising over 85% of all cases. PDAC has a relative 1-year survival rate of 20% and a 5-year survival rate of 4%. A better understanding of the molecular mechanisms leading to the development of pancreatic cancer remains a major goal for defining appropriate treatment strategies and earlier detection. Past studies have shown that members of the oncogenic Pim kinase family (Pim-1, Pim-2, and Pim-3) are aberrantly expressed in a variety of solid tumors, including pancreatic cancer. Currently, only Pim-1 and Pim-3 have been shown to be anti-apoptotic and aberrantly expressed in PDAC. Although members of the Pim kinase family have been shown to have a high degree of homology at the amino acid level, past studies have demonstrated functional differences among the members of the Pim family. To better understand the significance of these observations, we have investigated the role of Pims, including Pim-2, in growth transformation of pancreatic cancer. We hypothesize that inhibition of Pim-2 will be effective in antagonizing the aberrant growth of PDAC. Initially, we confirmed by western blot analysis that Pim-2 is aberrantly expressed in PDAC tissues and cell lines. Also, we found that inhibition of Pim-2 expression by shRNA resulted in decreased cell viability of PDAC cells. Additionally, inhibition of PIm-2 expression resulted in decreased anchorage-independent growth. These effects were further demonstrated by inhibiting Pim activity using novel small molecule Pim inhibitors developed by Jasco Pharmaceuticals that inhibit Pim-2 activity in the picomolar range. To begin to determine a mechanism for this growth inhibition, we studied the activity of various downstream substrates of Pim kinases in PDAC cells such as 4EBP-1. Overall our research continues to validate the role of Pim-2 in growth transformation, as well as further support Pim-2 as a viable target for drug therapy in pancreatic cancer. 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 86. doi:1538-7445.AM2012-86
FORMACIÓN EXPERIMENTAL DE LA DISECCIÓN ENDOSCÓPICA SUBMUCOSA
Authors: M Fernández-Bermejo, F Soria Gálvez, S Rodríguez Muñoz, JC Marín-Gabriel, JM Mateos Rodríguez, E Morcillo Martín, C Martín García, FM Sánchez-Margallo
Journal: Endoscopy (2011)

Objetivo: Mostrar nuestra experiencia de los últimos 4 años en la formación en modelo exvivo y animal de la disección endoscópica submucosa (DES).
Molecular Imaging of Chemokine Receptor CXCR4 in Non–Small Cell Lung Cancer Using 68Ga-Pentixafor PET/CT
Authors: Thorsten Derlin, Danny Jonigk, Johann Bauersachs, Frank M. Bengel
Journal: Clinical Nuclear Medicine (2016)

We report the case of a 62-year-old woman with a history of ST-elevation myocardial infarction who underwent 68Ga-Pentixafor PET/CT for characterization of postinfarct myocardial inflammation. 68Ga-Pentixafor PET/CT incidentally demonstrated marked CXCR4 expression in a space-occupying lesion in the right upper lobe. Corresponding 18F-FDG PET/CT showed increased metabolism, and subsequent biopsy revealed non-small cell lung cancer. Immunohistochemistry confirmed that CXCR4 was highly expressed on tumor cells. 68Ga-Pentixafor is a novel CXCR4-targeted probe for PET imaging of CXCR4-positive tumors and holds promise for tumor staging and prognostic stratification. CXCR4-targeted radionuclide therapy represents a therapy option in metastasized diseases.
Effect of Troglitazone in Insulin-Treated Patients with Type II Diabetes Mellitus
Authors: Sherwyn Schwartz, Philip Raskin, Vivian Fonseca, Jane F. Graveline
Journal: New England Journal of Medicine (1998)

Troglitazone is a new oral antidiabetic drug that increases the sensitivity of peripheral tissues to insulin. It may therefore increase the efficacy of exogenous insulin in patients with insulin-resistant diabetes mellitus.
TCT-424 Intraprocedural Ultrasound Evaluation of Both Radial and Ulnar Arteries and its Implication to Improve Success of Arterial Access from the Wrist: Anatomical Evaluation of a Consecutive Series of 566 Patients Undergoing Cardiac Catheterization and/or Percutaneous Coronary Intervention
Authors: Frederic Baumann, Jonathan S. Roberts
Journal: Journal of the American College of Cardiology (2015)
P32 Are junior doctors safe to perform pleural procedures? An audit of junior doctor knowledge and competency of pleural procedures before and after dedicated lecture-based and practical teaching sessions
Authors: S. V. Ruickbie, G. MacDonald, N. Walters, A. Draper, Y. E. Ong
Journal: Thorax (2011)

<h3>Introduction</h3> Pleural procedures are considered core competencies at the end of ST2 medical training but with the advent of sub-specialisation within medicine and reduced working hours, junior doctors may have less exposure to these procedures. <h3>Aims and Objectives</h3> One of the major themes that arose from the 2008 Rapid Response Report was inexperienced doctors undertaking procedures. We sought to determine the level of knowledge and competency at pleural procedures of junior doctors (F1-ST2) before and after teaching sessions to assess whether improvement occurred. <h3>Methods</h3> Junior doctors were asked to complete a questionnaire in early 2011 about their self-assessed level of competency at pleural procedures and testing knowledge on various aspects of chest drain insertion and removal. A series of lectures at “mandatory” teaching days and optional practical drain insertion sessions on animal cadavers were delivered and junior doctors were asked to repeat the questionnaire between June and July 2011. <h3>Results</h3> 57 doctors filled in the questionnaire pre-teaching and 37 completed in after teaching. Please see Abstract P32 table 1 for results. On re-audit, some of the most concerning findings were that 1 out of the 5 ST2 trainees had performed &lt;3 thoracocentesis and 3 out of the 5 had performed &lt;3 Seldinger chest drain insertion (1 never performed procedure) just prior to the completion of their ST2 rotation. <h3>Conclusion</h3> Dedicated teaching covering all aspects tested in the questionnaire led to an improvement in theoretical knowledge about pleural procedures but worrying basic deficiencies remain. It is uncertain whether the trainees had not attended teaching or had not absorbed the information. In addition junior doctors still perform relatively few pleural procedures. Of particular concern, some ST2s who are shortly to be medical SpRs have performed very few pleural procedures which are part of their core competency. Whether this is due to lack of opportunity due to reduction in hours or other factors is uncertain. This may represent a significant risk for patients presenting out of hours who require an emergency pleural procedure.