tbuckley/cabot-search huggingface dataset:
P1-11-04: Breast Cancer Treatment Resources and Guideline-Concordant Treatment in Appalachia.
Authors: N Yao, MM Hillemeier, RT Anderson, SA Matthews
Journal: Cancer Research (2011)

Abstract Background: Appalachia has poorer cancer outcomes, but little research has been done regarding availability of cancer care resources in this region and how resource availability may relate to cancer outcomes. This study 1) examines associations between radiation therapy resources and receipt of radiotherapy after BCS in counties within Kentucky — a SEER state; and 2) describes spatial patterning of breast cancer treatment resources in all 13 Appalachian states. Methods: For the Kentucky analyses, county-level data from the Area Resource File and SEER registry are analyzed. Bivariate analyses and spatial lag regression using a 6-nearest neighboring counties matrix are conducted. The sample includes stage I or II primary breast cancer patients age 18+ years diagnosed in Kentucky during 2000–2007. The dependent variable is the county-level percentage of patients received BCS without radiation; independent variables include density of radiation therapy providers and facilities and other socioeconomic covariates. For the analyses of entire Appalachian region, descriptive analyses and exploratory spatial data analysis are conducted including 420 Appalachian counties and 644 non-Appalachian counties in 13 states. Results: In Kentucky 16.44% of 17,227 early stage breast cancer patients received BCS without radiation therapy (21.08% in Appalachia versus 14.80% in non-Appalachia, p&amp;lt;0.001). Appalachian Kentucky had significantly fewer radiation oncologists and radiation therapy facilities per capita than non-Appalachian Kentucky. The number of radiation therapy facilities per capita is negatively associated with rates of BCS without radiation when controlling for covariates. Analysis of 13 Appalachian states shows that Appalachian counties, especially in the Central and Southern regions, had significant fewer physicians per capita in Surgery, Anesthesia, Clinical Pathology, and Radiation Oncology. Clustering of scarce breast cancer care resources was observed in Central Appalachia. Conclusions: Appalachian counties, especially in central Appalachia, have fewer breast cancer treatment resources than non-Appalachian counties, and resource availability is associated with cancer health disparities. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-11-04.
Abstract 2715: Treatment of disseminated HER-2 carcinomas with a HER-2-retargeted oncolytic herpes virus
Authors: Pier-Luigi Lollini, Laura Menotti, Carla De Giovanni, Marianna Ianzano, Arianna Palladini, Valentina Grosso, Stefania Croci, Giordano Nicoletti, Lorena Landuzzi, Valentina Gatta, Gabriella Campadelli Fiume, Patrizia Nanni
Journal: Cancer Research (2012)

Abstract Oncolytic viruses hold the promise to spare normal cells and to selectively seek and destroy tumor cells within the body. Until now numerous viruses where successfully engineered to confer or enhance tumor selectivity, however the effective targeting of disseminated tumor cells in vivo remains a major hurdle. We have retargeted herpes simpex virus (HSV) through the replacement of key gD sequences with sequences encoding a HER-2-specific single chain antibody derived from trastuzumab. The HER-2 retargeted virus (designated here as HER2-HSV) did not bind HSV natural receptors (HVEM and nectin-1), and exclusively infected and killed tumor cells expressing high levels of human HER-2 oncoprotein p185 (PNAS, 106: 9039, 2009). Intratumor injection of HER2-HSV inhibited the growth of HER-2+ human ovarian and breast carcinomas in immunodeficient mice. The aim of the present work was to assess the curative potential of HER2-HSV against disseminated tumors in realistic mouse models reflecting tumor spread in human patients. Human ovarian carcinoma SK-OV-3 cells implanted intraperitoneally in immunodeficient Rag2−/−;Il2rg−/− mice give rise to a progressive peritoneal carcinomatosis similar to the fatal condition developing in advanced human patients. Intraperitoneal (i.p.) administrations of HER2-HSV (108 pfu weekly for 4 weeks) strongly inhibited carcinomatosis resulting in 60% of mice free from peritoneal diffusion, and 95% reduction in the total weight of neoplastic nodules. Visceral organs are a common target of metastatic spread of breast cancer, therefore we studied whether HER2-HSV administred i.p. could treat visceral metastases of HER-2+ MDA-MB-453 breast carcinomas in Rag2−/−;Il2rg−/− mice. The incidence of ovarian metastases was reduced from 89% to 30% by HER2-HSV treatment. Interestingly, the antimetastatic activity of HER2-HSV was not confined to the peritoneal cavity. In the same mice we found also a significant reduction in brain metastases but not in bone marrow infiltration. In practice, HER2-HSV administered i.p. inhibited both visceral (ovary) and distant (brain) HER-2+ breast cancer metastases, presumably reflecting both intraperitoneal diffusion of the virus and the neurotropism of herpesviruses. We are currently studying whether the intravenous administration of HER2-HSV could achieve a more widespread control of metastatic growth.In conclusion, the results show that a HER-2-redirected oncolytic herpesvirus could effectively target disseminated ovarian and breast carcinomas. 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 2715. doi:1538-7445.AM2012-2715
Abstract LB-243: Functional oncogene identification in hematologic malignancies
Authors: Oliver Weigert, Andrew Lane, Nadja Kopp, Scott Rodig, Akinori Yoda, David M. Weinstock
Journal: Cancer Research (2011)

Abstract Next generation sequencing of hematologic malignancies has identified tens to hundreds of mutations in coding sequence per sample. However, the functional significance of nearly all of these mutations remains unclear. Importantly, systematic analyses to determine the phenotypic effects of somatic mutations from cancer samples have proven cumbersome and low-yield. We developed an alternate approach to efficiently identify functionally-important, cryptic alterations directly from hematologic malignancy specimens. In this system, retroviral cDNA libraries are constructed from patient samples and then used to infect the IL3-dependent B-cell line, BaF3. Expression of oncogenic kinases, transcription factors and other oncogenes results in IL3-independent survival, allowing for the isolation of individual transformed clones and sequencing of integrated cDNA. Streamlined methods for cDNA cloning and retroviral transduction have made it both feasible and cost-efficient to construct patient-specific libraries for oncogene identification. With this approach, cryptic mutations, translocations and other rearrangements with functional significance can be identified. We previously performed functional oncogene screening in a panel of precursor B-cell acute lymphoblastic leukemia (B-ALL) specimens with normal karyotypes. From our initial screen, we recovered an IL3-independent BaF3 clone that harbored a full-length mutant version of the cytokine receptor subunit CRLF2. We subsequently demonstrated that 5–10% of adult and pediatric B-ALL harbor CRLF2 alterations that frequently coincide with activating mutations in Janus kinase 2. With support from Stand Up To Cancer, we applied functional screening to 6 additional hematologic malignancy subtypes. We supplemented screening with limited exome sequencing of angioimmunoblastic T-cell lymphomas, biphenotypic acute leukemia and BALL to confirm the presence of functional alleles and recover possible cooperating mutations. With this approach, we identified a panel of alterations in these diseases and confirmed several to be somatic and functionally relevant, including novel mutations in JAK2, TYK2, IDH2 and FLT3. In addition, targeted sequencing identified the same nonsense mutation in an alpha kinase in multiple cases of angioimmunoblastic T-cell lymphoma. In conclusion, large-scale sequencing efforts are underway at many centers to identify somatic mutations in hematologic malignancy samples. Screening of retroviral cDNA libraries offers an efficient alternative, focused on phenotypically meaningful, and therefore potentially drugabble, alterations. 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 LB-243. doi:10.1158/1538-7445.AM2011-LB-243
PM-12 * Pax3 EXPRESSION ENHANCES PDGF-B-INDUCED BRAINSTEM GLIOMAGENESIS AND CHARACTERIZES A SUBSET OF BRAINSTEM GLIOMA
Authors: K. Misuraca, A. Diaz, S. Baker, O. Becher
Journal: Neuro-Oncology (2014)

High-grade Brainstem glioma (BSG), also known as Diffuse Intrinsic Pontine Glioma (DIPG), is an incurable pediatric brain cancer. Increasing evidence supports the existence of regional differences in gliomagenesis such that BSG is thought to be a distinct disease from glioma of the cerebral cortex (CG). In an effort to elucidate unique characteristics of BSG, we conducted expression analysis of mouse PDGF-B-driven BSG and CG initiated in Nestin progenitor cells and identified a short list of expression changes specific to the brainstem gliomagenesis process, including upregulation of paired box 3 (Pax3). In the neonatal mouse brain, while Pax3 expression is absent from the cerebral cortex, its expression marks a subset of brainstem progenitor cells, mirroring its regional expression in glioma. Ectopic expression of Pax3 in normal brainstem progenitors in vitro shows that Pax3 inhibits apoptosis. In vivo, Pax3 enhances PDGF-B-driven gliomagenesis by significantly shortening tumor latency (p = 0.02 by log rank test), and increasing tumor penetrance (from 25% to 80%, p = 0.0003 by Fisher's exact test), in a region-specific manner, while loss of Pax3 function in PDGF-B-driven;p53-deficient BSG significantly delays glioma formation (median survival of 38 versus 28.5 days, p = 0.0007 by log rank test). Importantly, Pax3 is regionally expressed in human glioma as well, with high PAX3 mRNA characterizing 40% of human BSG, revealing a subset of tumors that significantly associates with PDGFRA alterations and amplifications of cell cycle regulatory genes, and is exclusive of ACVR1 mutations. Collectively, these data suggest that regional Pax3 expression not only marks a novel subset of BSG but also contributes to PDGF-B-induced brainstem gliomagenesis.
Carbohydrate Metabolism in Normal Pregnancy
Authors: David Hurwitz, Dorothy Jensen
Journal: New England Journal of Medicine (1946)

GLYCOSURIA during pregnancy is such a frequent occurrence that it is often dismissed as unimportant. We have found, however, that true diabetes often begins during pregnancy and may be overlooked and that pre-existing diabetes is often made worse by pregnancy. These two facts prompted us to study the effect of normal pregnancy on carbohydrate metabolism.MethodTwenty-five healthy pregnant patients were taken at random from the clinic of the Boston Lying-in Hospital. Glucose-tolerance tests were done in each trimester of the pregnancy, one or two weeks after delivery and several months post partum. The capillary blood-sugar level was determined fasting . . .
TCT-561 Comparison Of Stent Axial Integrity In First- Versus Second-Generation Drug-Eluting Stents: Insights From An Intravascular Ultrasound Analysis
Authors: Hironori Kitabata, Joshua P. Loh, Lakshmana Pendyala, Salem Badr, Alfazir Omar, Israel Barbash, Sa'ar Minha, Marco A. Magalhaes, Hideaki Ota, Fang Chen, Rebecca Torguson, Lowell F. Satler, William O. Suddath, Kenneth Kent, Augusto Pichard, Ron Waksman
Journal: Journal of the American College of Cardiology (2013)
Ga-67 Imaging in Bone Marrow Hyperplasia
Authors: JOHN NGUYEN, JANIS OWENS, PANUKORN VASINRAPEE, MICHAEL SPIETH
Journal: Clinical Nuclear Medicine (1996)

Abnormal gallium uptake due to osteomyelitis is well documented. However, increased gallium uptake in bone marrow hyperplasia has never been reported. In bone marrow hyperplasia, there is expansion of the erythrons, as well as the reticuloendothelial system. Expansion of the reticuloendothelial system explains the increased sulfur colloid uptake. By the same reason, the expansion of the erythrons could explain the increased gallium uptake. This report demonstrates such a case in a patient with sickle cell anemia. It is important to consider this possibility to avoid overdiagnosing osteomyelitis in patient with bone marrow hyperplasia.
Vaccine Against Fungal Infections: Genetically Engineered Virus Nanofibers as an Efficient Vaccine for Preventing Fungal Infection (Adv. Healthcare Mater. 7/2016)
Authors: Yanyan Huai, Shuai Dong, Ye Zhu, Xin Li, Binrui Cao, Xiang Gao, Mingying Yang, Li Wang, Chuanbin Mao
Journal: Advanced Healthcare Materials (2016)

Injection of virus nanofibers into mice produces antibodies that can bind to the pathogenic fungus Candida albicans to inhibit fungal infection, as shown by M. Yang, L. Wang, C. B. Mao and colleagues on page 786, suggesting that virus nanofibers are effective vaccines for preventing fungal infections.
Spending on locums has risen 60% since 2009 in English emergency departments
Authors: A. O'Dowd
Journal: BMJ (2014)

NHS trusts in England are spending around 60% more on locum doctors to fill staffing gaps in hospital emergency departments than in 2009, new data show.

The Labour Party has released data showing that spending on emergency locums rose from £51.9m (€62.3m; $85.2m) in 2009-10 to £83.3m in 2012-13, a 60.2% rise.

Labour’s shadow health secretary, Andy Burnham, said that the figures were evidence of a “dangerous shortage” of emergency doctors.

Labour sent Freedom of Information Act requests to every hospital trust in England with an accident and emergency department and received responses from 107 of 145 trusts. The responses also showed that each trust spent on average £785 941 on emergency locums in 2012-13. …
Abstract 1446: Sonic hedgehog-associated medulloblastoma arising from the cochlear nuclei of the brainstem
Authors: Daniel Grammel, Monika Warmuth-Metz, André von Bueren, Marcel Kool, Torsten Pietsch, Hans Kretzschmar, David Rowitch, Stefan Rutkowski, Stefan Pfister, Ulrich Schüller
Journal: Cancer Research (2012)

Abstract Medulloblastoma is a malignant brain tumor of childhood that comprises at least four molecularly distinct subgroups. We have previously described that cerebellar granule neuron precursors may give rise to the subgroup with a molecular fingerprint of Sonic hedgehog (Shh) signaling. Other recent data indicate that precursor cells within the dorsal brain stem may serve as cellular origins for Wnt-associated medulloblastomas. In order to see whether Shh-associated medulloblastomas are also able to develop in the dorsal brainstem, we analyzed two lines of transgenic mice with constitutive Shh signaling in hGFAP- and Math1-positive brainstem precursor populations, respectively. Our results show that in both of these lines, medulloblastomas arise from granule neuron precursors of the cochlear nuclei, a derivative of the auditory lower rhombic lip. This region is distinct from derivatives of precerebellar lower rhombic lip where medulloblastoma arise in mice with constitutive-active Wnt signaling. With respect to their histology and the expression of appropriate markers, Shh tumors perfectly resemble the human counterparts. Moreover, we find that in a series of 63 human desmoplastic medulloblastomas, 19 (30%) have a very close contact to the cochlear nuclei on MRI imaging. In conclusion, we suggest that precursors of the rhombic lip which may either develop into cerebellar or into cochlear granule neurons, may give rise to Shh-associated medulloblastoma. 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 1446. doi:1538-7445.AM2012-1446
Aerosol Treatment of Bronchoconstriction in Children, with or without a Tube Spacer
Authors: Søren Pedersen
Journal: New England Journal of Medicine (1983)

To assess whether an extension tube between the aerosol source and the patient improves drug-inhalation therapy in children with acute bronchoconstriction, we treated 20 children under double-blind conditions with placebo or terbutaline delivered by a conventional aerosol or an aerosol with a tube spacer. Both terbutaline treatments resulted in a significant increase in forced expiratory volume in one second, as compared with placebo (P<0.001), but treatment with the tube-spacer aerosol produced significantly more improvement than did treatment with the conventional aerosol (P<0.01). The number of errors in inhalation technique was reduced when the spacer aerosol was used, and this reduction may account for the greater improvement in the children treated with the spacer. (N Engl J Med 1983; 308:1328–30.)
Abstract 1875: Identifying genetic variants contributing to cellular susceptibility to tamoxifen using a genome-wide cell-based model
Authors: Dana Ziliak, Liming Weng, Eric R. Gamazon, Hae Kyung Im, Zeruesenay Desta, Todd C. Skaar, David A. Flockhart, Rong Stephanie Huang
Journal: Cancer Research (2012)

Abstract Tamoxifen is one of the most commonly used agents in the treatment and prevention of estrogen receptor positive breast cancers. Beyond the presence of hormone receptors, there are no validated predictors of tamoxifen efficacy and toxicity. Therefore, we utilized a genome-wide cell-based model to comprehensively evaluate genetic variants for their contribution to cellular susceptibility to tamoxifen. Our model incorporates multi-dimensional datasets including genome-wide genotype, gene expression, and cellular growth inhibition following treatment in lymphoblastoid cell lines from the International HapMap project. Growth inhibition was measured using AlamarBlue Assay in 60 unrelated CEU (individuals of northern and western European decedent) and 60 unrelated YRI (individuals from Ibadan, Nigeria) samples. All cell lines were treated with increasing concentrations of endoxifen, an active metabolite of tamoxifen, for 72 hours. Log2 transformed percent survival at each concentration and IC50 were used as cellular susceptibility to drug phenotypes. A step-wise genome-wide association studies were performed among SNPs, mRNA expression, and endoxifen sensitivity phenotypes. We identified 10 and 74 SNPs associated with endoxifen sensitivity through the expression of 13 and 92 genes in the separate CEU and YRI population. Interestingly 3 genes (STS, TES and SMARCA2) identified through this method are known to play a role in hormone biosynthesis pathway. Furthermore, a large portion of identified genes was found to play a role in tamoxifen sensitivity in the NCI60 cancer cell lines including CHPT1, a known tumor progression marker. This approach has made possible the identification of genetic variants/genes that have not been previously associated with tamoxifen response. Further validation of these cell-based model findings may significantly improve our ability to predict tamoxifen treatment efficacy and toxicity in breast cancer patients. 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 1875. doi:1538-7445.AM2012-1875
Genetic Differences in the Immediate Transcriptome Response to Stress Predict Risk-Related Brain Function and Psychiatric Disorders
Authors: Janine Arloth, Ryan Bogdan, Peter Weber, Goar Frishman, Andreas Menke, Klaus V. Wagner, Georgia Balsevich, Mathias V. Schmidt, Nazanin Karbalai, Darina Czamara, Andre Altmann, Dietrich Trümbach, Wolfgang Wurst, Divya Mehta, Manfred Uhr, Torsten Klengel, Angelika Erhardt, Caitlin E. Carey, Emily Drabant Conley, Andreas Ruepp, Bertram Müller-Myhsok, Ahmad R. Hariri, Elisabeth B. Binder, Stephan Ripke, Naomi R. Wray, Cathryn M. Lewis, Steven P. Hamilton, Myrna M. Weissman, Gerome Breen, Enda M. Byrne, Douglas H.R. Blackwood, Dorret I. Boomsma, Sven Cichon, Andrew C. Heath, Florian Holsboer, Susanne Lucae, Pamela A.F. Madden, Nicholas G. Martin, Peter McGuffin, Pierandrea Muglia, Markus M. Noethen, Brenda P. Penninx, Michele L. Pergadia, James B. Potash, Marcella Rietschel, Danyu Lin, Bertram Müller-Myhsok, Jianxin Shi, Stacy Steinberg, Hans J. Grabe, Paul Lichtenstein, Patrik Magnusson, Roy H. Perlis, Martin Preisig, Jordan W. Smoller, Kari Stefansson, Rudolf Uher, Zoltan Kutalik, Katherine E. Tansey, Alexander Teumer, Alexander Viktorin, Michael R. Barnes, Thomas Bettecken, Elisabeth B. Binder, René Breuer, Victor M. Castro, Susanne E. Churchill, William H. Coryell, Nick Craddock, Ian W. Craig, Darina Czamara, Eco J. De Geus, Franziska Degenhardt, Anne E. Farmer, Maurizio Fava, Josef Frank, Vivian S. Gainer, Patience J. Gallagher, Scott D. Gordon, Sergey Goryachev, Magdalena Gross, Michel Guipponi, Anjali K. Henders, Stefan Herms, Ian B. Hickie, Susanne Hoefels, Witte Hoogendijk, Jouke Jan Hottenga, Dan V. Iosifescu, Marcus Ising, Ian Jones, Lisa Jones, Tzeng Jung-Ying, James A. Knowles, Isaac S. Kohane, Martin A. Kohli, Ania Korszun, Mikael Landen, William B. Lawson, Glyn Lewis, Donald MacIntyre, Wolfgang Maier, Manuel Mattheisen, Patrick J. McGrath, Andrew McIntosh, Alan McLean, Christel M. Middeldorp, Lefkos Middleton, Grant M. Montgomery, Shawn N. Murphy, Matthias Nauck, Willem A. Nolen, Dale R. Nyholt, Michael O’Donovan, Högni Oskarsson, Nancy Pedersen, William A. Scheftner, Andrea Schulz, Thomas G. Schulze, Stanley I. Shyn, Engilbert Sigurdsson, Susan L. Slager, Johannes H. Smit, Hreinn Stefansson, Michael Steffens, Thorgeir Thorgeirsson, Federica Tozzi, Jens Treutlein, Manfred Uhr, Edwin J.C.G. van den Oord, Gerard Van Grootheest, Henry Völzke, Jeffrey B. Weilburg, Gonneke Willemsen, Frans G. Zitman, Benjamin Neale, Mark Daly, Douglas F. Levinson, Patrick F. Sullivan
Journal: Neuron (2015)
Editorial pour endoscopy
Authors: C Cellier
Journal: Endoscopy (2013)

L'endoscopie digestive est le cœur de métier de plus de 80% des hépato-gastro-entérologues français. Lors des Journées Francophones d'Hépato-Gastro-Entérologie et d'Oncologie Digestive (JFHOD) en mars 2013 à Paris, seront présentés de nombreux travaux de recherche en endoscopie digestive. Ceux-ci représentent le dynamisme de l'activité de recherche qui existe en France sur cette thématique.