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Sample records for invasive progression identified

  1. Expression profiling of in vivo ductal carcinoma in situ progression models identified B cell lymphoma-9 as a molecular driver of breast cancer invasion

    OpenAIRE

    Elsarraj, Hanan S.; Hong, Yan; Valdez, Kelli E.; Michaels, Whitney; Hook, Marcus; Smith, William P.; Chien, Jeremy; Herschkowitz, Jason I.; Troester, Melissa A.; Beck, Moriah; Inciardi, Marc; Gatewood, Jason; May, Lisa; Cusick, Therese; McGinness, Marilee

    2015-01-01

    Introduction: There are an estimated 60,000 new cases of ductal carcinoma in situ (DCIS) each year. A lack of understanding in DCIS pathobiology has led to overtreatment of more than half of patients. We profiled the temporal molecular changes during DCIS transition to invasive ductal carcinoma (IDC) using in vivo DCIS progression models. These studies identified B cell lymphoma-9 (BCL9) as a potential molecular driver of early invasion. BCL9 is a newly found co-activator of Wnt-stimulated β-...

  2. Coronin-1C is a novel biomarker for hepatocellular carcinoma invasive progression identified by proteomics analysis and clinical validation

    Directory of Open Access Journals (Sweden)

    Chen Liang-Dong

    2010-02-01

    Full Text Available Abstract Background To better search for potential markers for hepatocellular carcinoma (HCC invasion and metastasis, proteomic approach was applied to identify potential metastasis biomarkers associated with HCC. Methods Membrane proteins were extracted from MHCC97L and HCCLM9 cells, with a similar genetic background and remarkably different metastasis potential, and compared by SDS-PAGE and identified by ESI-MS/MS. The results were further validated by western blot analysis, immunohistochemistry (IHC of tumor tissues from HCCLM9- and MHCC97L-nude mice, and clinical specimens. Results Membrane proteins were extracted from MHCC97L and HCCLM9 cell and compared by SDS-PAGE analyses. A total of 14 differentially expressed proteins were identified by ESI-MS/MS. Coronin-1C, a promising candidate, was found to be overexpressed in HCCLM9 cells as compared with MHCC97L cells, and validated by western blot and IHC from both nude mice tumor tissues and clinical specimens. Coronin-1C level showed an abrupt upsurge when pulmonary metastasis occurred. Increasing coronin-1C expression was found in liver cancer tissues of HCCLM9-nude mice with spontaneous pulmonary metastasis. IHC study on human HCC specimens revealed that more patients in the higher coronin-1C group had overt larger tumor and more advanced stage. Conclusions Coronin-1C could be a candidate biomarker to predict HCC invasive behavior.

  3. Expression microarray meta-analysis identifies genes associated with Ras/MAPK and related pathways in progression of muscle-invasive bladder transition cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Jonathan A Ewald

    Full Text Available The effective detection and management of muscle-invasive bladder Transition Cell Carcinoma (TCC continues to be an urgent clinical challenge. While some differences of gene expression and function in papillary (Ta, superficial (T1 and muscle-invasive (≥T2 bladder cancers have been investigated, the understanding of mechanisms involved in the progression of bladder tumors remains incomplete. Statistical methods of pathway-enrichment, cluster analysis and text-mining can extract and help interpret functional information about gene expression patterns in large sets of genomic data. The public availability of patient-derived expression microarray data allows open access and analysis of large amounts of clinical data. Using these resources, we investigated gene expression differences associated with tumor progression and muscle-invasive TCC. Gene expression was calculated relative to Ta tumors to assess progression-associated differences, revealing a network of genes related to Ras/MAPK and PI3K signaling pathways with increased expression. Further, we identified genes within this network that are similarly expressed in superficial Ta and T1 stages but altered in muscle-invasive T2 tumors, finding 7 genes (COL3A1, COL5A1, COL11A1, FN1, ErbB3, MAPK10 and CDC25C whose expression patterns in muscle-invasive tumors are consistent in 5 to 7 independent outside microarray studies. Further, we found increased expression of the fibrillar collagen proteins COL3A1 and COL5A1 in muscle-invasive tumor samples and metastatic T24 cells. Our results suggest that increased expression of genes involved in mitogenic signaling may support the progression of muscle-invasive bladder tumors that generally lack activating mutations in these pathways, while expression changes of fibrillar collagens, fibronectin and specific signaling proteins are associated with muscle-invasive disease. These results identify potential biomarkers and targets for TCC treatments, and

  4. HumanMethylation450K Array–Identified Biomarkers Predict Tumour Recurrence/Progression at Initial Diagnosis of High-risk Non-muscle Invasive Bladder Cancer

    Science.gov (United States)

    Kitchen, Mark O; Bryan, Richard T; Emes, Richard D; Luscombe, Christopher J; Cheng, KK; Zeegers, Maurice P; James, Nicholas D; Gommersall, Lyndon M; Fryer, Anthony A

    2018-01-01

    Background: High-risk non-muscle invasive bladder cancer (HR-NMIBC) is a clinically unpredictable disease. Despite clinical risk estimation tools, many patients are undertreated with intra-vesical therapies alone, whereas others may be over-treated with early radical surgery. Molecular biomarkers, particularly DNA methylation, have been reported as predictive of tumour/patient outcomes in numerous solid organ and haematologic malignancies; however, there are few reports in HR-NMIBC and none using genome-wide array assessment. We therefore sought to identify novel DNA methylation markers of HR-NMIBC clinical outcomes that might predict tumour behaviour at initial diagnosis and help guide patient management. Patients and methods: A total of 21 primary initial diagnosis HR-NMIBC tumours were analysed by Illumina HumanMethylation450 BeadChip arrays and subsequently bisulphite Pyrosequencing. In all, 7 had not recurred at 1 year after resection and 14 had recurred and/or progressed despite intra-vesical BCG. A further independent cohort of 32 HR-NMIBC tumours (17 no recurrence and 15 recurrence and/or progression despite BCG) were also assessed by bisulphite Pyrosequencing. Results: Array analyses identified 206 CpG loci that segregated non-recurrent HR-NMIBC tumours from clinically more aggressive recurrence/progression tumours. Hypermethylation of CpG cg11850659 and hypomethylation of CpG cg01149192 in combination predicted HR-NMIBC recurrence and/or progression within 1 year of diagnosis with 83% sensitivity, 79% specificity, and 83% positive and 79% negative predictive values. Conclusions: This is the first genome-wide DNA methylation analysis of a unique HR-NMIBC tumour cohort encompassing known 1-year clinical outcomes. Our analyses identified potential novel epigenetic markers that could help guide individual patient management in this clinically unpredictable disease. PMID:29343995

  5. HumanMethylation450K Array-Identified Biomarkers Predict Tumour Recurrence/Progression at Initial Diagnosis of High-risk Non-muscle Invasive Bladder Cancer.

    Science.gov (United States)

    Kitchen, Mark O; Bryan, Richard T; Emes, Richard D; Luscombe, Christopher J; Cheng, K K; Zeegers, Maurice P; James, Nicholas D; Gommersall, Lyndon M; Fryer, Anthony A

    2018-01-01

    High-risk non-muscle invasive bladder cancer (HR-NMIBC) is a clinically unpredictable disease. Despite clinical risk estimation tools, many patients are undertreated with intra-vesical therapies alone, whereas others may be over-treated with early radical surgery. Molecular biomarkers, particularly DNA methylation, have been reported as predictive of tumour/patient outcomes in numerous solid organ and haematologic malignancies; however, there are few reports in HR-NMIBC and none using genome-wide array assessment. We therefore sought to identify novel DNA methylation markers of HR-NMIBC clinical outcomes that might predict tumour behaviour at initial diagnosis and help guide patient management. A total of 21 primary initial diagnosis HR-NMIBC tumours were analysed by Illumina HumanMethylation450 BeadChip arrays and subsequently bisulphite Pyrosequencing. In all, 7 had not recurred at 1 year after resection and 14 had recurred and/or progressed despite intra-vesical BCG. A further independent cohort of 32 HR-NMIBC tumours (17 no recurrence and 15 recurrence and/or progression despite BCG) were also assessed by bisulphite Pyrosequencing. Array analyses identified 206 CpG loci that segregated non-recurrent HR-NMIBC tumours from clinically more aggressive recurrence/progression tumours. Hypermethylation of CpG cg11850659 and hypomethylation of CpG cg01149192 in combination predicted HR-NMIBC recurrence and/or progression within 1 year of diagnosis with 83% sensitivity, 79% specificity, and 83% positive and 79% negative predictive values. This is the first genome-wide DNA methylation analysis of a unique HR-NMIBC tumour cohort encompassing known 1-year clinical outcomes. Our analyses identified potential novel epigenetic markers that could help guide individual patient management in this clinically unpredictable disease.

  6. HumanMethylation450K Array–Identified Biomarkers Predict Tumour Recurrence/Progression at Initial Diagnosis of High-risk Non-muscle Invasive Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Mark O Kitchen

    2018-01-01

    Full Text Available Background: High-risk non-muscle invasive bladder cancer (HR-NMIBC is a clinically unpredictable disease. Despite clinical risk estimation tools, many patients are undertreated with intra-vesical therapies alone, whereas others may be over-treated with early radical surgery. Molecular biomarkers, particularly DNA methylation, have been reported as predictive of tumour/patient outcomes in numerous solid organ and haematologic malignancies; however, there are few reports in HR-NMIBC and none using genome-wide array assessment. We therefore sought to identify novel DNA methylation markers of HR-NMIBC clinical outcomes that might predict tumour behaviour at initial diagnosis and help guide patient management. Patients and methods: A total of 21 primary initial diagnosis HR-NMIBC tumours were analysed by Illumina HumanMethylation450 BeadChip arrays and subsequently bisulphite Pyrosequencing. In all, 7 had not recurred at 1 year after resection and 14 had recurred and/or progressed despite intra-vesical BCG. A further independent cohort of 32 HR-NMIBC tumours (17 no recurrence and 15 recurrence and/or progression despite BCG were also assessed by bisulphite Pyrosequencing. Results: Array analyses identified 206 CpG loci that segregated non-recurrent HR-NMIBC tumours from clinically more aggressive recurrence/progression tumours. Hypermethylation of CpG cg11850659 and hypomethylation of CpG cg01149192 in combination predicted HR-NMIBC recurrence and/or progression within 1 year of diagnosis with 83% sensitivity, 79% specificity, and 83% positive and 79% negative predictive values. Conclusions: This is the first genome-wide DNA methylation analysis of a unique HR-NMIBC tumour cohort encompassing known 1-year clinical outcomes. Our analyses identified potential novel epigenetic markers that could help guide individual patient management in this clinically unpredictable disease.

  7. Prognosis of muscle-invasive bladder cancer: difference between primary and progressive tumours and implications for therapy.

    NARCIS (Netherlands)

    Schrier, B.P.; Hollander, M.P.; Rhijn, B.W. van; Kiemeney, L.A.L.M.; Witjes, J.A.

    2004-01-01

    OBJECTIVE: To evaluate the difference in prognosis between progressive and primary muscle-invasive bladder cancer. MATERIALS AND METHODS: From 1986 to 2000, 74 patients with progressive muscle-invasive bladder cancer were identified. Eighty-nine patients with primary muscle-invasive bladder cancer

  8. DNA barcoding of invasive plants in China: A resource for identifying invasive plants.

    Science.gov (United States)

    Xu, Song-Zhi; Li, Zhen-Yu; Jin, Xiao-Hua

    2018-01-01

    Invasive plants have aroused attention globally for causing ecological damage and having a negative impact on the economy and human health. However, it can be extremely challenging to rapidly and accurately identify invasive plants based on morphology because they are an assemblage of many different families and many plant materials lack sufficient diagnostic characteristics during border inspections. It is therefore urgent to evaluate candidate loci and build a reliable genetic library to prevent invasive plants from entering China. In this study, five common single markers (ITS, ITS2, matK, rbcL and trnH-psbA) were evaluated using 634 species (including 469 invasive plant species in China, 10 new records to China, 16 potentially invasive plant species around the world but not introduced into China yet and 139 plant species native to China) based on three different methods. Our results indicated that ITS2 displayed largest intra- and interspecific divergence (1.72% and 91.46%). Based on NJ tree method, ITS2, ITS, matK, rbcL and trnH-psbA provided 76.84%, 76.5%, 63.21%, 52.86% and 50.68% discrimination rates, respectively. The combination of ITS + matK performed best and provided 91.03% discriminatory power, followed by ITS2 + matK (85.78%). For identifying unknown individuals, ITS + matK had 100% correct identification rate based on our database, followed by ITS/ITS2 (both 93.33%) and ITS2 + matK (91.67%). Thus, we propose ITS/ITS2 + matK as the most suitable barcode for invasive plants in China. This study also demonstrated that DNA barcoding is an efficient tool for identifying invasive species. © 2017 John Wiley & Sons Ltd.

  9. Identifying Invasive Species Educational Needs in Florida: Opportunities for Extension

    Science.gov (United States)

    Huang, Pei-wen; Lamm, Alexa J.

    2016-01-01

    Florida's ecology has been adversely affected by invasive species. In Florida, a study was conducted to explore opportunities for Extension educators to contribute to combating the issue of invasive species. Florida residents' responses were captured through the use of an online public opinion survey. The findings revealed a need for invasive…

  10. Defining progression in nonmuscle invasive bladder cancer: it is time for a new, standard definition.

    Science.gov (United States)

    Lamm, Donald; Persad, Raj; Brausi, Maurizio; Buckley, Roger; Witjes, J Alfred; Palou, Joan; Böhle, Andreas; Kamat, Ashish M; Colombel, Marc; Soloway, Mark

    2014-01-01

    Despite being one of the most important clinical outcomes in nonmuscle invasive bladder cancer, there is currently no standard definition of disease progression. Major clinical trials and meta-analyses have used varying definitions or have failed to define this end point altogether. A standard definition of nonmuscle invasive bladder cancer progression as determined by reproducible and reliable procedures is needed. We examine current definitions of nonmuscle invasive bladder cancer progression, and propose a new definition that will be more clinically useful in determining patient prognosis and comparing treatment options. The IBCG (International Bladder Cancer Group) analyzed published clinical trials and meta-analyses that examined nonmuscle invasive bladder cancer progression as of December 2012. The limitations of the definitions of progression used in these trials were considered, as were additional parameters associated with the advancement of nonmuscle invasive bladder cancer. The most commonly used definition of nonmuscle invasive bladder cancer progression is an increase in stage from nonmuscle invasive to muscle invasive disease. Although this definition is clinically important, it fails to include other important parameters of advancing disease such as progression to lamina propria invasion and increase in grade. The IBCG proposes the definition of nonmuscle invasive bladder cancer progression as an increase in T stage from CIS or Ta to T1 (lamina propria invasion), development of T2 or greater or lymph node (N+) disease or distant metastasis (M1), or an increase in grade from low to high. Investigators should consider the use of this new definition to help standardize protocols and improve the reporting of progression. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  11. Association of C-MYC amplification with progression from the in situ to the invasive stage in C-MYC-amplified breast carcinomas

    NARCIS (Netherlands)

    Robanus-Maandag, Els C.; Bosch, Cathy A. J.; Kristel, Petra M.; Hart, Augustinus A. M.; Faneyte, Ian F.; Nederlof, Petra M.; Peterse, Johannes L.; van de Vijver, Marc J.

    2003-01-01

    Human carcinoma in situ of the breast already demonstrates genomic changes found in invasive lesions. However, no specific genetic alterations have previously been identified that are associated with progression from the in situ to the invasive stage. By comparative genomic hybridization (CGH) and

  12. Total RNA Sequencing Analysis of DCIS Progressing to Invasive Breast Cancer

    Science.gov (United States)

    2015-09-01

    Assay Kits respectively on the Qubit 2.0 Fluorometer (Life Technologies). The BioRad Experion Automated Electrophoresis System RNA kit was used to...AWARD NUMBER: W81XWH-14-1-0080 TITLE: Total RNA Sequencing Analysis of DCIS Progressing to Invasive Breast Cancer. PRINCIPAL INVESTIGATOR...Aug 2015 4. TITLE AND SUBTITLE Total RNA Sequencing Analysis of DCIS Progressing to Invasive Breast Cancer. 5a. CONTRACT NUMBER 5b. GRANT

  13. Plant invasion science in protected areas: progress and priorities

    Czech Academy of Sciences Publication Activity Database

    Foxcroft, L. C.; Pyšek, Petr; Richardson, D. M.; Genovesi, P.; MacFadyen, S.

    2017-01-01

    Roč. 19, č. 5 (2017), s. 1353-1378 ISSN 1387-3547 R&D Projects: GA ČR GB14-36079G Grant - others:AV ČR(CZ) AP1002 Program:Akademická prémie - Praemium Academiae Institutional support: RVO:67985939 Keywords : plant invasions * global patterns * protected areas Subject RIV: EH - Ecology, Behaviour OBOR OECD: Biodiversity conservation Impact factor: 2.473, year: 2016

  14. Molecular Markers Increase Precision of the European Association of Urology Non-Muscle-Invasive Bladder Cancer Progression Risk Groups.

    Science.gov (United States)

    van Kessel, Kim E M; van der Keur, Kirstin A; Dyrskjøt, Lars; Algaba, Ferran; Welvaart, Naeromy Y C; Beukers, Willemien; Segersten, Ulrika; Keck, Bastian; Maurer, Tobias; Simic, Tatjana; Horstmann, Marcus; Grimm, Marc-Oliver; Hermann, Gregers G; Mogensen, Karin; Hartmann, Arndt; Harving, Niels; Petersen, Astrid C; Jensen, Jørgen B; Junker, Kerstin; Boormans, Joost L; Real, Francisco X; Malats, Núria; Malmström, Per-Uno; Ørntoft, Torben F; Zwarthoff, Ellen C

    2018-01-24

    Purpose: The European Association of Urology (EAU) guidelines for non-muscle-invasive bladder cancer (NMIBC) recommend risk stratification based on clinicopathologic parameters. Our aim was to investigate the added value of biomarkers to improve risk stratification of NMIBC. Experimental Design: We prospectively included 1,239 patients in follow-up for NMIBC in six European countries. Fresh-frozen tumor samples were analyzed for GATA2, TBX2, TBX3 , and ZIC4 methylation and FGFR3, TERT, PIK3CA , and RAS mutation status. Cox regression analyses identified markers that were significantly associated with progression to muscle-invasive disease. The progression incidence rate (PIR = rate of progression per 100 patient-years) was calculated for subgroups. Results: In our cohort, 276 patients had a low, 273 an intermediate, and 555 a high risk of tumor progression based on the EAU NMIBC guideline. Fifty-seven patients (4.6%) progressed to muscle-invasive disease. The limited number of progressors in this large cohort compared with older studies is likely due to improved treatment in the past two decades. Overall, wild-type FGFR3 and methylation of GATA2 and TBX3 were significantly associated with progression (HR = 0.34, 2.53, and 2.64, respectively). The PIR for EAU high-risk patients was 4.25. On the basis of FGFR3 mutation status and methylation of GATA2 , this cohort could be reclassified into a good class (PIR = 0.86, 26.2% of patients), a moderate class (PIR = 4.32, 49.7%), and a poor class (PIR = 7.66, 24.0%). Conclusions: We conclude that the addition of selected biomarkers to the EAU risk stratification increases its accuracy and identifies a subset of NMIBC patients with a very high risk of progression. Clin Cancer Res; 1-8. ©2018 AACR. ©2018 American Association for Cancer Research.

  15. The WIP1 oncogene promotes progression and invasion of aggressive medulloblastoma variants.

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    Buss, M C; Remke, M; Lee, J; Gandhi, K; Schniederjan, M J; Kool, M; Northcott, P A; Pfister, S M; Taylor, M D; Castellino, R C

    2015-02-26

    Recent studies suggest that medulloblastoma, the most common malignant brain tumor of childhood, is comprised of four disease variants. The WIP1 oncogene is overexpressed in Group 3 and 4 tumors, which contain medulloblastomas with the most aggressive clinical behavior. Our data demonstrate increased WIP1 expression in metastatic medulloblastomas, and inferior progression-free and overall survival of patients with WIP1 high-expressing medulloblastoma. Microarray analysis identified upregulation of genes involved in tumor metastasis, including the G protein-coupled receptor CXCR4, in medulloblastoma cells with high WIP1 expression. Stimulation with the CXCR4 ligand SDF1α activated PI-3 kinase signaling, and promoted growth and invasion of WIP1 high-expressing medulloblastoma cells in a p53-dependent manner. When xenografted into the cerebellum of immunodeficient mice, medulloblastoma cells with stable or endogenous high WIP1 expression exhibited strong expression of CXCR4 and activated AKT in primary and invasive tumor cells. WIP1 or CXCR4 knockdown inhibited medulloblastoma growth and invasion. WIP1 knockdown also improved the survival of mice xenografted with WIP1 high-expressing medulloblastoma cells. WIP1 knockdown inhibited cell surface localization of CXCR4 by suppressing expression of the G protein receptor kinase 5, GRK5. Restoration of wild-type GRK5 promoted Ser339 phosphorylation of CXCR4 and inhibited the growth of WIP1-stable medulloblastoma cells. Conversely, GRK5 knockdown inhibited Ser339 phosphorylation of CXCR4, increased cell surface localization of CXCR4 and promoted the growth of medulloblastoma cells with low WIP1 expression. These results demonstrate crosstalk among WIP1, CXCR4 and GRK5, which may be important for the aggressive phenotype of a subclass of medulloblastomas in children.

  16. Implications of Rho GTPase signaling in glioma cell invasion and tumor progression

    Directory of Open Access Journals (Sweden)

    Shannon Patricia Fortin Ensign

    2013-10-01

    Full Text Available Glioblastoma (GB is the most malignant of primary adult brain tumors, characterized by a highly locally-invasive cell population, as well as abundant proliferative cells, neoangiogenesis, and necrosis. Clinical intervention with chemotherapy or radiation may either promote or establish an environment for manifestation of invasive behavior. Understanding the molecular drivers of invasion in the context of glioma progression may be insightful in directing new treatments for patients with GB. Here, we review current knowledge on Rho family GTPases, their aberrant regulation in GB, and their effect on GB cell invasion and tumor progression. Rho GTPases are modulators of cell migration through effects on actin cytoskeleton rearrangement; in non-neoplastic tissue, expression and activation of Rho GTPases are normally under tight regulation. In GB, Rho GTPases are deregulated, often via hyperactivity or overexpression of their activators, Rho GEFs. Downstream effectors of Rho GTPases have been shown to promote invasiveness and, importantly, glioma cell survival. The study of aberrant Rho GTPase signaling in GB is thus an important investigation of cell invasion as well as treatment resistance and disease progression.

  17. Clonal expansion and linear genome evolution through breast cancer progression from pre-invasive stages to asynchronous metastasis

    DEFF Research Database (Denmark)

    Krøigård, Anne Bruun; Larsen, Martin Jakob; Lænkholm, Anne-Vibeke

    2015-01-01

    necessitates knowledge of the degree of genomic concordance between different steps of malignant progression as primary tumors often are used as surrogates of systemic disease. Based on exome sequencing we performed copy number profiling and point mutation detection on successive steps of breast cancer...... progression from one breast cancer patient, including two different regions of Ductal Carcinoma In Situ (DCIS), primary tumor and an asynchronous metastasis. We identify a remarkable landscape of somatic mutations, retained throughout breast cancer progression and with new mutational events emerging at each......Evolution of the breast cancer genome from pre-invasive stages to asynchronous metastasis is complex and mostly unexplored, but highly demanded as it may provide novel markers for and mechanistic insights in cancer progression. The increasing use of personalized therapy of breast cancer...

  18. Comprehensive expression profiling of tumor cell lines identifies molecular signatures of melanoma progression.

    Directory of Open Access Journals (Sweden)

    Byungwoo Ryu

    2007-07-01

    of transcripts are novel. In addition, the transcription factor NF-KB was specifically identified as being a potential "master regulator" of melanoma invasion since NF-KB binding sites were identified as consistent consensus sequences within promoters of progression-associated genes.We conclude that tumor cell lines are a valuable resource for the early identification of gene signatures associated with malignant progression in tumors with significant heterogeneity like melanoma. We further conclude that the development of novel data reduction algorithms for analysis of microarray studies is critical to allow for optimized mining of important, clinically-relevant datasets. It is expected that subsequent validation studies in primary human tissues using such an approach will lead to more rapid translation of such studies to the identification of novel tumor biomarkers and therapeutic targets.

  19. Identifying highly connected counties compensates for resource limitations when evaluating national spread of an invasive pathogen.

    Directory of Open Access Journals (Sweden)

    Sweta Sutrave

    Full Text Available Surveying invasive species can be highly resource intensive, yet near-real-time evaluations of invasion progress are important resources for management planning. In the case of the soybean rust invasion of the United States, a linked monitoring, prediction, and communication network saved U.S. soybean growers approximately $200 M/yr. Modeling of future movement of the pathogen (Phakopsora pachyrhizi was based on data about current disease locations from an extensive network of sentinel plots. We developed a dynamic network model for U.S. soybean rust epidemics, with counties as nodes and link weights a function of host hectarage and wind speed and direction. We used the network model to compare four strategies for selecting an optimal subset of sentinel plots, listed here in order of increasing performance: random selection, zonal selection (based on more heavily weighting regions nearer the south, where the pathogen overwinters, frequency-based selection (based on how frequently the county had been infected in the past, and frequency-based selection weighted by the node strength of the sentinel plot in the network model. When dynamic network properties such as node strength are characterized for invasive species, this information can be used to reduce the resources necessary to survey and predict invasion progress.

  20. Identifying highly connected counties compensates for resource limitations when evaluating national spread of an invasive pathogen.

    Science.gov (United States)

    Sutrave, Sweta; Scoglio, Caterina; Isard, Scott A; Hutchinson, J M Shawn; Garrett, Karen A

    2012-01-01

    Surveying invasive species can be highly resource intensive, yet near-real-time evaluations of invasion progress are important resources for management planning. In the case of the soybean rust invasion of the United States, a linked monitoring, prediction, and communication network saved U.S. soybean growers approximately $200 M/yr. Modeling of future movement of the pathogen (Phakopsora pachyrhizi) was based on data about current disease locations from an extensive network of sentinel plots. We developed a dynamic network model for U.S. soybean rust epidemics, with counties as nodes and link weights a function of host hectarage and wind speed and direction. We used the network model to compare four strategies for selecting an optimal subset of sentinel plots, listed here in order of increasing performance: random selection, zonal selection (based on more heavily weighting regions nearer the south, where the pathogen overwinters), frequency-based selection (based on how frequently the county had been infected in the past), and frequency-based selection weighted by the node strength of the sentinel plot in the network model. When dynamic network properties such as node strength are characterized for invasive species, this information can be used to reduce the resources necessary to survey and predict invasion progress.

  1. Genetic networks inducing invasive growth in Saccharomyces cerevisiae identified through systematic genome-wide overexpression.

    Science.gov (United States)

    Shively, Christian A; Eckwahl, Matthew J; Dobry, Craig J; Mellacheruvu, Dattatreya; Nesvizhskii, Alexey; Kumar, Anuj

    2013-04-01

    The budding yeast Saccharomyces cerevisiae can respond to nutritional and environmental stress by implementing a morphogenetic program wherein cells elongate and interconnect, forming pseudohyphal filaments. This growth transition has been studied extensively as a model signaling system with similarity to processes of hyphal development that are linked with virulence in related fungal pathogens. Classic studies have identified core pseudohyphal growth signaling modules in yeast; however, the scope of regulatory networks that control yeast filamentation is broad and incompletely defined. Here, we address the genetic basis of yeast pseudohyphal growth by implementing a systematic analysis of 4909 genes for overexpression phenotypes in a filamentous strain of S. cerevisiae. Our results identify 551 genes conferring exaggerated invasive growth upon overexpression under normal vegetative growth conditions. This cohort includes 79 genes lacking previous phenotypic characterization. Pathway enrichment analysis of the gene set identifies networks mediating mitogen-activated protein kinase (MAPK) signaling and cell cycle progression. In particular, overexpression screening suggests that nuclear export of the osmoresponsive MAPK Hog1p may enhance pseudohyphal growth. The function of nuclear Hog1p is unclear from previous studies, but our analysis using a nuclear-depleted form of Hog1p is consistent with a role for nuclear Hog1p in repressing pseudohyphal growth. Through epistasis and deletion studies, we also identified genetic relationships with the G2 cyclin Clb2p and phenotypes in filamentation induced by S-phase arrest. In sum, this work presents a unique and informative resource toward understanding the breadth of genes and pathways that collectively constitute the molecular basis of filamentation.

  2. Identifying Molecular Culprits of Cervical Cancer Progression | Center for Cancer Research

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    Human papillomavirus (HPV) DNA is found in 99.7% of invasive cervical carcinomas, providing strong evidence that the virus is a causative agent in the development of this disease. However, most women who become infected with HPV do not develop invasive cervical lesions, indicating that additional exogenous or genetic factors may determine whether HPV preclinical lesions will progress to cancer. Identification of these factors would be facilitated by a deeper understanding of the cellular and molecular changes that accompany progression to malignancy. In addition, knowledge of which women are at greatest risk for disease progression would be a significant clinical advancement in the management of patients with premalignant cervical lesions.

  3. Defining progression in nonmuscle invasive bladder cancer: it is time for a new, standard definition

    NARCIS (Netherlands)

    Lamm, D.; Persad, R.; Brausi, M.; Buckley, R.; Witjes, J.A.; Palou, J.; Bohle, A.; Kamat, A.M.; Colombel, M.; Soloway, M.

    2014-01-01

    PURPOSE: Despite being one of the most important clinical outcomes in nonmuscle invasive bladder cancer, there is currently no standard definition of disease progression. Major clinical trials and meta-analyses have used varying definitions or have failed to define this end point altogether. A

  4. [Application progress of minimally invasive technique in treatment of calcaneus fractures].

    Science.gov (United States)

    Yu, Tao; Yang, Yunfeng; Yu, Guangrong

    2013-02-01

    To review the application progress of minimally invasive technique in the treatment of calcaneus fractures and to analyze the advantages and disadvantages of each method as well as to predict the trend of development in the field. Domestic and abroad literature concerning the minimally invasive technique applied in calcaneus fractures in recent years was reviewed extensively and analyzed thoroughly. There are both advantages and limitations of each minimally invasive technique including percutaneous reduction and fixation, limited incision, external fixator, arthroscopic assisted reduction, and balloon expansion reduction. But every technique is developing rapidly and becoming more and more effective. A variety of minimally invasive technique can not only be used independently but also can be applied jointly to complement one another. It needs further study how to improve the effectiveness and expand the indications. And the theoretical basis of evidence-based medicine needs to be provided more.

  5. Identifying knowledge gaps for gene drive research to control invasive animal species: The next CRISPR step

    Directory of Open Access Journals (Sweden)

    Dorian Moro

    2018-01-01

    Full Text Available Invasive animals have been linked to the extinctions of native wildlife, and to significant agricultural financial losses or impacts. Current approaches to control invasive species require ongoing resources and management over large geographic scales, and often result in the short-term suppression of populations. New and innovative approaches are warranted. Recently, the RNA guided gene drive system based on CRISPR/Cas9 is being proposed as a potential gene editing tool that could be used by wildlife managers as a non-lethal addition or alternative to help reduce pest animal populations. While regulatory control and social acceptance are crucial issues that must be addressed, there is an opportunity now to identify the knowledge and research gaps that exist for some important invasive species. Here we systematically determine the knowledge gaps for pest species for which gene drives could potentially be applied. We apply a conceptual ecological risk framework within the gene drive context within an Australian environment to identify key requirements for undertaking work on seven exemplar invasive species in Australia. This framework allows an evaluation of the potential research on an invasive species of interest and within a gene drive and risk context. We consider the currently available biological, genetic and ecological information for the house mouse, European red fox, feral cat, European rabbit, cane toad, black rat and European starling to evaluate knowledge gaps and identify candidate species for future research. We discuss these findings in the context of future thematic areas of research worth pursuing in preparation for a more formal assessment of the use of gene drives as a novel strategy for the control of these and other invasive species. Keywords: Invasive species, Gene drive, CRISPR, Pest management, Islands

  6. Focal degeneration of basal cells and the resultant auto-immunoreactions: a novel mechanism for prostate tumor progression and invasion.

    Science.gov (United States)

    Man, Yan-Gao; Gardner, William A

    2008-01-01

    The development of human prostate cancer is believed to be a multistep process, progressing sequentially from normal, to hyperplasia, to prostatic intraepithelial neoplasia (PIN), and to invasive and metastatic lesions. High grade PIN has been generally considered as the direct precursor of invasive lesions, and the progression of PIN is believed to be triggered primarily, if not solely, by the overproduction of proteolytic enzymes predominately by cancer cells, which result in the degradation of the basement membrane. These theories, however, are hard to reconcile with two main facts: (1) only about 30% untreated PIN progress to invasive stage, while none of the current approaches could accurately identify the specific PIN or individuals at greater risk for progression, and (2) results from recent world-wide clinical trials with a wide variety of proteolytic enzyme inhibitors have been very disappointing, casting doubt on the validity of the proteolytic enzyme theory. Since over 90% of prostate cancer-related deaths result from invasion-related illness and the incidence of PIN could be up to 16.5-25% in routine or ultrasound guided prostate biopsy, there is an urgent need to uncover the intrinsic mechanism of prostate tumor invasion. Promoted by the facts that the basal cell population is the source of several tumor suppressors and the absence of the basal cell layer is the most distinct feature of invasive lesions, our recent studies have intended to identify the early alterations of basal cell layers and their impact on tumor invasion using multidisciplinary approaches. Our studies revealed that a subset of pre-invasive tumors contained focal disruptions (the absence of basal cells resulting in a gap greater than the combined size of at least three epithelial cells) in surrounding basal cell layers. Compared to their non-disrupted counterparts, focally disrupted basal cell layers had several unique features: (1) significantly lower proliferation; (2

  7. Total RNA Sequencing Analysis of DCIS Progressing to Invasive Breast Cancer

    Science.gov (United States)

    2017-09-01

    collaboration with Affymetrix scientists , we were able to determine Q/C measures that are predictive of subsequent array data quality, but at the cost... fact progress to invasive disease (IBC), and complements our multi-institutional, NIH-funded study of genetic and epigenetic alterations of pre...information we are seeking, because only the strongest signals were detectable in our data. In collaboration with Affymetrix scientists , we were able to

  8. Total RNA Sequencing Analysis of DCIS Progressing to Invasive Breast Cancer

    Science.gov (United States)

    2016-09-01

    for Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT: This project is designed to complement a multi-institutional, NIH...the minority of cases of preinvasive breast cancer (DCIS), that do in fact progress to invasive disease (IBC), and complements our multi-institutional...Pathology & Laboratory Medicine Lineberger Comprehensive Cancer Center 125 Mason Farm Road The University of North Carolina at Chapel Hill Chapel

  9. Three-dimensional modelling identifies novel genetic dependencies associated with breast cancer progression in the isogenic MCF10 model.

    Science.gov (United States)

    Maguire, Sarah L; Peck, Barrie; Wai, Patty T; Campbell, James; Barker, Holly; Gulati, Aditi; Daley, Frances; Vyse, Simon; Huang, Paul; Lord, Christopher J; Farnie, Gillian; Brennan, Keith; Natrajan, Rachael

    2016-11-01

    The initiation and progression of breast cancer from the transformation of the normal epithelium to ductal carcinoma in situ (DCIS) and invasive disease is a complex process involving the acquisition of genetic alterations and changes in gene expression, alongside microenvironmental and recognized histological alterations. Here, we sought to comprehensively characterise the genomic and transcriptomic features of the MCF10 isogenic model of breast cancer progression, and to functionally validate potential driver alterations in three-dimensional (3D) spheroids that may provide insights into breast cancer progression, and identify targetable alterations in conditions more similar to those encountered in vivo. We performed whole genome, exome and RNA sequencing of the MCF10 progression series to catalogue the copy number and mutational and transcriptomic landscapes associated with progression. We identified a number of predicted driver mutations (including PIK3CA and TP53) that were acquired during transformation of non-malignant MCF10A cells to their malignant counterparts that are also present in analysed primary breast cancers from The Cancer Genome Atlas (TCGA). Acquisition of genomic alterations identified MYC amplification and previously undescribed RAB3GAP1-HRAS and UBA2-PDCD2L expressed in-frame fusion genes in malignant cells. Comparison of pathway aberrations associated with progression showed that, when cells are grown as 3D spheroids, they show perturbations of cancer-relevant pathways. Functional interrogation of the dependency on predicted driver events identified alterations in HRAS, PIK3CA and TP53 that selectively decreased cell growth and were associated with progression from preinvasive to invasive disease only when cells were grown as spheroids. Our results have identified changes in the genomic repertoire in cell lines representative of the stages of breast cancer progression, and demonstrate that genetic dependencies can be uncovered when cells

  10. GENOTYPICALY IDENTIFYING WHEAT MESOPHYLL CONDUCTANCE REGULATION UNDER PROGRESSIVE DROUGHT STRESS

    Directory of Open Access Journals (Sweden)

    Katarina Olsovska

    2016-08-01

    Full Text Available AbstractPhotosynthesis limitation by CO2 flow constraints from sub-stomatal cavities to carboxylation sites in chloroplasts under drought stress conditions is, at least in some plant species or crops not fully understood, yet. Leaf mesophyll conductance for CO2 (gm may considerably affect both photosynthesis and water use efficiency in plants under drought conditions. The aim of our study was to detect the responses of gm in leaves of four winter wheat (Triticum aestivum L. genotypes from different origins under long-term progressive drought. Based on the measurement of gas-exchange parameters the variability of genotypic responses was analyzed at stomatal (stomata closure and non-stomatal (diffusional and biochemical limits of net CO2 assimilation rate (AN. In general, progressive drought caused an increasing leaf diffusion resistance against CO2 flow leading to the decrease of AN, gm and stomatal conductance (gs, respectively. Reduction of gm also led to inhibition of carboxylation efficiency (Vcmax. On the basis of achieved results a strong positive relationship between gm and gs was found out indicating a co-regulation and mutual independence of the relationship under the drought conditions. In severely stressed plants, the stomatal limitation of the CO2 assimilation rate was progressively increased, but to a less extent in comparison to gm, while a non-stomatal limitation became more dominant due to the prolonged drought. Mesophyll conductance (gm seems to be a suitable mechanism and parameter for selection of improved diffusional properties and photosynthetic carbon assimilation in C3 plants, thus explaining their better photosynthetic performance at a whole plant level during periods of drought.

  11. Slug contributes to cadherin switch and malignant progression in muscle-invasive bladder cancer development.

    Science.gov (United States)

    Wu, Kaijie; Zeng, Jin; Zhou, Jiancheng; Fan, Jinhai; Chen, Yule; Wang, Zhiqiang; Zhang, TingTing; Wang, Xinyang; He, Dalin

    2013-11-01

    The Snail family of zinc finger transcription factors (i.e., Snail and Slug) predicts the tumor recurrence in superficial bladder cancers, while their roles in the development of muscle-invasion, metastasis, and chemoresistance in muscle-invasive bladder cancers with poor prognosis have not been investigated. This study evaluates the clinical significance of Slug in aggressive bladder cancer. A pair of sublines (i.e., T24-P and T24-L) from a unique orthotropic metastatic model of bladder cancer was firstly utilized to identify the potential precursors contributing to those aggressive phenotypes. The coexpression of Slug, E-cadherin, and N-cadherin in bladder cancer cell lines (i.e., 5637, RT4, 253 J, J82, and T24) and tissues was evaluated by reverse transcription-polymerase chain reaction (RT-PCR), Western blotting, and immunohistochemistry staining analysis. The function of Slug expression on E- to N-cadherin switch, cell invasion, and chemoresistance to proapoptotic treatment was validated by gain-in-function and knockdown strategy in vitro. Slug was identified as one of the novel targets contributed to the aggressive phenotypes of T24-L cells, which showed enhanced cell invasive, metastatic, and chemoresistant potentials in vitro and in vivo as previously described. Up-regulation of Slug was significantly correlated with a higher tumor stage and the E- to N-cadherin switch in bladder cancer cells and tissues, whereas ectopic expression of Slug in bladder cancer 5637 and RT-4 cell lines promoted epithelial-to-mesenchymal transition (EMT), increased cell invasiveness and chemoresistance. By contrast, knocking down Slug using siRNA in T24-L cell lines reversed these changes. Slug elevates in invasive or metastatic bladder cancer and plays a critical role in EMT via control of cadherin switch. Slug may be a potential marker or target for improving the diagnosis and treatment of muscle-invasive bladder cancers. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. HYAL-1 Hyaluronidase: A Potential Prognostic Indicator for Progression to Muscle Invasion and Recurrence in Bladder Cancer

    Science.gov (United States)

    Kramer, Mario W.; Golshani, Roozbeh; Merseburger, Axel S.; Knapp, Judith; Garcia, Alfredo; Hennenlotter, Joerg; Duncan, Robert C.; Soloway, Mark S.; Jorda, Merce; Kuczyk, Marcus A.; Stenzl, Arnulf; Lokeshwar, Vinata B

    2009-01-01

    Background For bladder cancer (BCa) patients undergoing bladder-sparing treatments, molecular markers may aid in accurately predicting progression to muscle invasion and recurrence. Hyaluronic acid (HA) is a glycosaminoglycan that promotes tumor metastasis. Hyaluronoglucosaminidase 1 (HYAL-1)–type hyaluronidase (HAase) promotes tumor growth, invasion, and angiogenesis. Urinary HA and HAase levels are diagnostic markers for BCa. Objective We evaluated whether HA and HYAL-1 can predict progression to muscle invasion and recurrence among patients with non–muscle-invasive BCa. Design, setting, and participants Based on tissue availability, tissue microarrays were prepared from a cohort of 178 BCa specimens (144 non–muscle invasive, 34 muscle invasive). Follow-up information was available on 111 patients with non–muscle-invasive BCa (mean follow-up: 69.5 mo); 58 patients recurred and 25 progressed to muscle invasion (mean time to progress: 22.3 mo). Measurements HA and HYAL-1 expression was evaluated by immunohistochemistry and graded for intensity and area of staining. Association of HA and HYAL-1 staining with BCa recurrence and muscle invasion was evaluated by univariate and multivariate models. Results and limitations HA and HYAL-1 expression correlated with tumor grade, stage, and multifocality (p < 0.05). In non–muscle-invasive BCa specimens, HYAL-1 staining was higher (234.3 ± 52.2; 200.6 ± 61.4) if patients experienced progression to muscle invasion or recurrence when compared with no progression or recurrence (164.1 ± 48.2; 172.1 ± 57; p < 0.001). HA staining correlated with muscle invasion (p < 0.001). In univariate analysis, age (p = 0.014), multifocality (p = 0.023), and HYAL-1 staining (p < 0.001) correlated with muscle invasion, whereas only HYAL-1 correlated with recurrence (p = 0.013). In multivariate analysis, significantly associated with muscle invasion (p < 0.001; 76.8% accuracy) and recurrence (p = 0.01; 67.8% accuracy). Conclusions

  13. Identifying Quality in Preschool Education: Progress and Challenge

    Science.gov (United States)

    Hughes, Jan N.

    2010-01-01

    In this article, the author comments on Dominguez, Vitiello, Maier, and Greenfield's (2010) article on identifying quality in preschool education. Dominguez et al. have conducted a methodologically sophisticated study describing the growth of learning behavior among Head Start children. By doing so, they contribute to a growing body of evidence…

  14. Transformed Recombinant Enrichment Profiling Rapidly Identifies HMW1 as an Intracellular Invasion Locus in Haemophilus influenzae

    Science.gov (United States)

    Moleres, Javier; Sinha, Sunita; Fernández-Calvet, Ariadna; Porsch, Eric A.; St. Geme, Joseph W.; Nislow, Corey; Redfield, Rosemary J.; Garmendia, Junkal

    2016-01-01

    Many bacterial species actively take up and recombine homologous DNA into their genomes, called natural competence, a trait that offers a means to identify the genetic basis of naturally occurring phenotypic variation. Here, we describe “transformed recombinant enrichment profiling” (TREP), in which natural transformation is used to generate complex pools of recombinants, phenotypic selection is used to enrich for specific recombinants, and deep sequencing is used to survey for the genetic variation responsible. We applied TREP to investigate the genetic architecture of intracellular invasion by the human pathogen Haemophilus influenzae, a trait implicated in persistence during chronic infection. TREP identified the HMW1 adhesin as a crucial factor. Natural transformation of the hmw1 operon from a clinical isolate (86-028NP) into a laboratory isolate that lacks it (Rd KW20) resulted in ~1,000-fold increased invasion into airway epithelial cells. When a distinct recipient (Hi375, already possessing hmw1 and its paralog hmw2) was transformed by the same donor, allelic replacement of hmw2A Hi375 by hmw1A 86-028NP resulted in a ~100-fold increased intracellular invasion rate. The specific role of hmw1A 86-028NP was confirmed by mutant and western blot analyses. Bacterial self-aggregation and adherence to airway cells were also increased in recombinants, suggesting that the high invasiveness induced by hmw1A 86-028NP might be a consequence of these phenotypes. However, immunofluorescence results found that intracellular hmw1A 86-028NP bacteria likely invaded as groups, instead of as individual bacterial cells, indicating an emergent invasion-specific consequence of hmw1A-mediated self-aggregation. PMID:27124727

  15. Identifying the mechanisms of intron gain: progress and trends

    Directory of Open Access Journals (Sweden)

    Yenerall Paul

    2012-09-01

    Full Text Available Abstract Continued improvements in Next-Generation DNA/RNA sequencing coupled with advances in gene annotation have provided researchers access to a plethora of annotated genomes. Subsequent analyses of orthologous gene structures have identified numerous intron gain and loss events that have occurred both recently and in the very distant past. This research has afforded exceptional insight into the temporal and lineage-specific rates of intron gain and loss among various species throughout evolution. Numerous studies have also attempted to identify the molecular mechanisms of intron gain and loss. However, even after considerable effort, very little is known about these processes. In particular, the mechanism(s of intron gain have proven exceptionally enigmatic and remain topics of considerable debate. Currently, there exists no definitive consensus as to what mechanism(s may generate introns. Because many introns are known to affect gene expression, it is necessary to understand the molecular process(es by which introns may be gained. Here we review the seven most commonly purported mechanisms of intron gain and, when possible, summarize molecular evidence for or against the occurrence of each of these mechanisms. Furthermore, we catalogue indirect evidence that supports the occurrence of each mechanism. Finally, because these proposed mechanisms fail to explain the mechanistic origin of many recently gained introns, we also look at trends that may aid researchers in identifying other potential mechanism(s of intron gain. Reviewers This article was reviewed by Eugene Koonin, Scott Roy (nominated by W. Ford Doolittle, and John Logsdon.

  16. Identifying genes for neurobehavioural traits in rodents: progress and pitfalls

    Directory of Open Access Journals (Sweden)

    Amelie Baud

    2017-04-01

    Full Text Available Identifying genes and pathways that contribute to differences in neurobehavioural traits is a key goal in psychiatric research. Despite considerable success in identifying quantitative trait loci (QTLs associated with behaviour in laboratory rodents, pinpointing the causal variants and genes is more challenging. For a long time, the main obstacle was the size of QTLs, which could encompass tens if not hundreds of genes. However, recent studies have exploited mouse and rat resources that allow mapping of phenotypes to narrow intervals, encompassing only a few genes. Here, we review these studies, showcase the rodent resources they have used and highlight the insights into neurobehavioural traits provided to date. We discuss what we see as the biggest challenge in the field – translating QTLs into biological knowledge by experimentally validating and functionally characterizing candidate genes – and propose that the CRISPR/Cas genome-editing system holds the key to overcoming this obstacle. Finally, we challenge traditional views on inbred versus outbred resources in the light of recent resource and technology developments.

  17. Human mitochondrial NAD(P)(+)-dependent malic enzyme participates in cutaneous melanoma progression and invasion.

    Science.gov (United States)

    Chang, Yung-Lung; Gao, Hong-Wei; Chiang, Chien-Ping; Wang, Wei-Ming; Huang, Shih-Ming; Ku, Chien-Fen; Liu, Guang-Yaw; Hung, Hui-Chih

    2015-03-01

    Cutaneous melanoma is the most life-threatening neoplasm of the skin, accounting for most of the skin cancer deaths. Accumulating evidence suggests that targeting metabolism is an appealing strategy for melanoma therapy. Mitochondrial NAD(P)(+)-dependent malic enzyme (ME2), an oxidative decarboxylase, was evaluated for its biological significance in cutaneous melanoma progression. ME2 mRNA and protein expression significantly increased during melanoma progression, as evidenced by Gene Expression Omnibus analysis and immunohistochemistry on clinically annotated tissue microarrays, respectively. In addition, ME2 knockdown attenuated melanoma cell proliferation in vitro. ME2 ablation resulted in reduced cellular ATP levels and elevated cellular reactive oxygen species production, which activated the AMP-activated protein kinase pathway and inhibited acetyl-CoA carboxylase. Furthermore, ME2 expression was associated with cell migration and invasion. ME2 knockdown decreased anchorage-independent growth in vitro and tumor cell growth in vivo. These results suggested that ME2 might be an important factor in melanoma progression and a novel biomarker of invasion.

  18. Validation of Algorithms to Identify Invasive Electrophysiology Procedures Using Administrative Data in Ontario, Canada.

    Science.gov (United States)

    Singh, Sheldon M; Webster, Lauren; Calzavara, Andrew; Wijeysundera, Harindra C

    2017-06-01

    Administrative database research can provide insight into the real-world effectiveness of invasive electrophysiology procedures. However, no validated algorithm to identify these procedures within administrative data currently exists. To develop and validate algorithms to identify atrial fibrillation (AF), atrial flutter (AFL), supraventricular tachycardia (SVT) catheter ablation procedures, and diagnostic electrophysiology studies (EPS) within administrative data. Algorithms consisting of physician procedural billing codes and their associated most responsible hospital diagnosis codes were used to identify potential AF, AFL, SVT catheter ablation procedures and diagnostic EPS within large administrative databases in Ontario, Canada. The potential procedures were then limited to those performed between October 1, 2011 and March 31, 2013 at a single large regional cardiac center (Sunnybrook Health Sciences Center) in Ontario, Canada. These procedures were compared with a gold-standard cohort of patients known to have undergone invasive electrophysiology procedures during the same time period at the same institution. The sensitivity, specificity, positive and negative predictive values of each algorithm was determined. Algorithms specific to each of AF, AFL, and SVT ablation were associated with a moderate sensitivity (75%-86%), high specificity (95%-98%), positive (95%-98%), and negative (99%) predictive values. The best algorithm to identify diagnostic EPS was less optimal with a sensitivity of 61% and positive predictive value of 88%. Algorithms using a combination of physician procedural billing codes and accompanying most responsible hospital diagnosis may identify catheter ablation procedures within administrative data with a high degree of accuracy. Diagnostic EPS may be identified with reduced accuracy.

  19. Elevated expression of LSD1 (Lysine-specific demethylase 1 during tumour progression from pre-invasive to invasive ductal carcinoma of the breast

    Directory of Open Access Journals (Sweden)

    Serce Nuran

    2012-08-01

    Full Text Available Abstract Background Lysine-specific demethylase1 (LSD1 is a nuclear protein which belongs to the aminooxidase-enzymes playing an important role in controlling gene expression. It has also been found highly expressed in several human malignancies including breast carcinoma. Our aim was to detect LSD1 expression also in pre-invasive neoplasias of the breast. In the current study we therefore analysed LSD1 protein expression in ductal carcinoma in situ (DCIS in comparison to invasive ductal breast cancer (IDC. Methods Using immunohistochemistry we systematically analysed LSD1 expression in low grade DCIS (n = 27, intermediate grade DCIS (n = 30, high grade DCIS (n = 31 and in invasive ductal breast cancer (n = 32. SPSS version 18.0 was used for statistical analysis. Results LSD1 was differentially expressed in DCIS and invasive ductal breast cancer. Interestingly, LSD1 was significantly overexpressed in high grade DCIS versus low grade DCIS. Differences in LSD1 expression levels were also statistically significant between low/intermediate DCIS and invasive ductal breast carcinoma. Conclusions LSD1 is also expressed in pre-invasive neoplasias of the breast. Additionally, there is a gradual increase of LSD1 expression within tumour progression from pre-invasive DCIS to invasive ductal breast carcinoma. Therefore upregulation of LSD1 may be an early tumour promoting event.

  20. Intertwining of Activin A and TGFβ Signaling: Dual Roles in Cancer Progression and Cancer Cell Invasion

    Energy Technology Data Exchange (ETDEWEB)

    Loomans, Holli A. [Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Andl, Claudia D., E-mail: claudia.andl@vanderbilt.edu [Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Department of Surgery, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Vanderbilt Digestive Disease Center, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Vanderbilt Epithelial Biology Center, Vanderbilt University Medical Center, Nashville, TN 37232 (United States)

    2014-12-30

    In recent years, a significant amount of research has examined the controversial role of activin A in cancer. Activin A, a member of the transforming growth factor β (TGFβ) superfamily, is best characterized for its function during embryogenesis in mesoderm cell fate differentiation and reproduction. During embryogenesis, TGFβ superfamily ligands, TGFβ, bone morphogenic proteins (BMPs) and activins, act as potent morphogens. Similar to TGFβs and BMPs, activin A is a protein that is highly systemically expressed during early embryogenesis; however, post-natal expression is overall reduced and remains under strict spatiotemporal regulation. Of importance, normal post-natal expression of activin A has been implicated in the migration and invasive properties of various immune cell types, as well as endometrial cells. Aberrant activin A signaling during development results in significant morphological defects and premature mortality. Interestingly, activin A has been found to have both oncogenic and tumor suppressor roles in cancer. Investigations into the role of activin A in prostate and breast cancer has demonstrated tumor suppressive effects, while in lung and head and neck squamous cell carcinoma, it has been consistently shown that activin A expression is correlated with increased proliferation, invasion and poor patient prognosis. Activin A signaling is highly context-dependent, which is demonstrated in studies of epithelial cell tumors and the microenvironment. This review discusses normal activin A signaling in comparison to TGFβ and highlights how its dysregulation contributes to cancer progression and cell invasion.

  1. Expression of monoacylglycerol lipase as a marker of tumour invasion and progression in malignant melanoma.

    Science.gov (United States)

    Baba, Yuko; Funakoshi, T; Mori, M; Emoto, K; Masugi, Y; Ekmekcioglu, S; Amagai, M; Tanese, K

    2017-12-01

    Accumulating evidence suggests that the lipid lytic enzyme monoacylglycerol lipase (MAGL) promotes tumour invasion and metastasis through up-regulation of pro-tumorigenic signalling lipids in several tumour cell lines. However, the expression status of MAGL in clinical melanoma tissues and its clinicopathological significance remain unclear. To correlate the tumour expression status of MAGL with the clinicopathological information of patients with malignant melanoma. Polymerase chain reaction (PCR) array screening was performed, and the results were validated using immunocytochemical analysis of tumour and non-tumour melanocytic cell lines. Immunohistochemical staining for MAGL was performed for 74 melanoma samples, including 48 primary and 26 metastatic tumours, in which the expression of MAGL was determined by evaluating the percentage of MAGL-positive tumour cells and the MAGL staining intensity. Finally, we analysed the association of MAGL expression status with tumour progression, tumour thickness and vascular invasion of the primary lesion. Immunocytochemical analysis revealed that MAGL was expressed in all 12 melanoma cell lines, but not in normal human epidermal melanocytes. In the immunohistochemical analysis, positive staining for MAGL was noted in 32 of 48 (64.5%) primary lesions, 14 of 17 (82.4%) lymph node metastatic lesions and 7 of 9 (77.8%) skin metastatic lesions. Metastatic tumours had a significantly higher staining intensity (P = 0.033 for lymph node, P = 0.010 for skin). In the analysis of primary lesions, higher MAGL expression correlated with greater tumour thickness (P = 0.015) and the presence of vascular invasion (P = 0.017). On further evaluation of MAGL-positive primary lesions, staining intensity of MAGL tended to be higher in deeper areas of the tumour mass. The expression of MAGL in tumour cells reflects the aggressiveness of melanoma cells and may serve as a marker of tumour progression. © 2017 European Academy of Dermatology and

  2. Whole-Genome Sequencing of Invasion-Resistant Cells Identifies Laminin α2 as a Host Factor for Bacterial Invasion

    DEFF Research Database (Denmark)

    van Wijk, Xander M.; Döhrmann, Simon; Hallstrom, Bjorn

    2017-01-01

    To understand the role of glycosaminoglycans in bacterial cellular invasion, xylosyltransferase-deficient mutants of Chinese hamster ovary (CHO) cells were created using clustered regularly interspaced short palindromic repeat (CRISPR) and CRISPR-associated gene 9 (CRISPR-cas9) gene targeting. When...... these mutants were compared to the pgsA745 cell line, a CHO xylosyltransferase mutant generated previously using chemical mutagenesis, an unexpected result was obtained. Bacterial invasion of pgsA745 cells by group B Streptococcus (GBS), group A Streptococcus, and Staphylococcus aureus was markedly reduced...... compared to the invasion of wild-type cells, but newly generated CRISPR-cas9 mutants were only resistant to GBS. Invasion of pgsA745 cells was not restored by transfection with xylosyltransferase, suggesting that an additional mutation conferring panresistance to multiple bacteria was present in pgsA745...

  3. Prognostic Impact of a 12-gene Progression Score in Non-muscle-invasive Bladder Cancer: A Prospective Multicentre Validation Study.

    Science.gov (United States)

    Dyrskjøt, Lars; Reinert, Thomas; Algaba, Ferran; Christensen, Emil; Nieboer, Daan; Hermann, Gregers G; Mogensen, Karin; Beukers, Willemien; Marquez, Mirari; Segersten, Ulrika; Høyer, Søren; Ulhøi, Benedicte P; Hartmann, Arndt; Stöhr, Robert; Wach, Sven; Nawroth, Roman; Schwamborn, Kristina; Tulic, Cane; Simic, Tatjana; Junker, Kerstin; Harving, Niels; Petersen, Astrid C; Jensen, Jørgen B; Keck, Bastian; Grimm, Marc-Oliver; Horstmann, Marcus; Maurer, Tobias; Steyerberg, Ewout W; Zwarthoff, Ellen C; Real, Francisco X; Malats, Núria; Malmström, Per-Uno; Ørntoft, Torben F

    2017-09-01

    Progression of non-muscle-invasive bladder cancer (NMIBC) to muscle-invasive bladder cancer (MIBC) is life-threatening and cannot be accurately predicted using clinical and pathological risk factors. Biomarkers for stratifying patients to treatment and surveillance are greatly needed. To validate a previously developed 12-gene progression score to predict progression to MIBC in a large, multicentre, prospective study. We enrolled 1224 patients in ten European centres between 2008 and 2012. A total of 750 patients (851 tumours) fulfilled the inclusion and sample quality criteria for testing. Patients were followed for an average of 28 mo (range 0-76). A 12-gene real-time qualitative polymerase chain reaction assay was performed for all tumours and progression scores were calculated using a predefined formula and cut-off values. We measured progression to MIBC using Cox regression analysis and log-rank tests for comparing survival distributions. The progression score was significantly (prisk score, and disease progression. Univariate Cox regression analysis showed that patients molecularly classified as high risk experienced more frequent disease progression (hazard ratio 5.08, 95% confidence interval 2.2-11.6; prisk factors (prisk factors, and may help in stratifying NMIBC patients to optimise treatment and follow-up regimens. Clinical use of a 12-gene molecular test for disease aggressiveness may help in stratifying patients with non-muscle-invasive bladder cancer to optimal treatment regimens. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  4. Urban landscape genomics identifies fine-scale gene flow patterns in an avian invasive.

    Science.gov (United States)

    Low, G W; Chattopadhyay, B; Garg, K M; Irestedt, M; Ericson, Pgp; Yap, G; Tang, Q; Wu, S; Rheindt, F E

    2018-01-01

    Invasive species exert a serious impact on native fauna and flora and have been the target of many eradication and management efforts worldwide. However, a lack of data on population structure and history, exacerbated by the recency of many species introductions, limits the efficiency with which such species can be kept at bay. In this study we generated a novel genome of high assembly quality and genotyped 4735 genome-wide single nucleotide polymorphic (SNP) markers from 78 individuals of an invasive population of the Javan Myna Acridotheres javanicus across the island of Singapore. We inferred limited population subdivision at a micro-geographic level, a genetic patch size (~13-14 km) indicative of a pronounced dispersal ability, and barely an increase in effective population size since introduction despite an increase of four to five orders of magnitude in actual population size, suggesting that low population-genetic diversity following a bottleneck has not impeded establishment success. Landscape genomic analyses identified urban features, such as low-rise neighborhoods, that constitute pronounced barriers to gene flow. Based on our data, we consider an approach targeting the complete eradication of Javan Mynas across Singapore to be unfeasible. Instead, a mixed approach of localized mitigation measures taking into account urban geographic features and planning policy may be the most promising avenue to reducing the adverse impacts of this urban pest. Our study demonstrates how genomic methods can directly inform the management and control of invasive species, even in geographically limited datasets with high gene flow rates.

  5. Understanding the Progression of Bone Metastases to Identify Novel Therapeutic Targets

    Directory of Open Access Journals (Sweden)

    Annie Schmid-Alliana

    2018-01-01

    Full Text Available Bone is one of the most preferential target site for cancer metastases, particularly for prostate, breast, kidney, lung and thyroid primary tumours. Indeed, numerous chemical signals and growth factors produced by the bone microenvironment constitute factors promoting cancer cell invasion and aggression. After reviewing the different theories proposed to provide mechanism for metastatic progression, we report on the gene expression profile of bone-seeking cancer cells. We also discuss the cross-talk between the bone microenvironment and invading cells, which impacts on the tumour actions on surrounding bone tissue. Lastly, we detail therapies for bone metastases. Due to poor prognosis for patients, the strategies mainly aim at reducing the impact of skeletal-related events on patients’ quality of life. However, recent advances have led to a better understanding of molecular mechanisms underlying bone metastases progression, and therefore of novel therapeutic targets.

  6. Near infrared imaging to identify sentinel lymph nodes in invasive urinary bladder cancer

    Science.gov (United States)

    Knapp, Deborah W.; Adams, Larry G.; Niles, Jacqueline D.; Lucroy, Michael D.; Ramos-Vara, Jose; Bonney, Patty L.; deGortari, Amalia E.; Frangioni, John V.

    2006-02-01

    Approximately 12,000 people are diagnosed with invasive transitional cell carcinoma of the urinary bladder (InvTCC) each year in the United States. Surgical removal of the bladder (cystectomy) and regional lymph node dissection are considered frontline therapy. Cystectomy causes extensive acute morbidity, and 50% of patients with InvTCC have occult metastases at the time of diagnosis. Better staging procedures for InvTCC are greatly needed. This study was performed to evaluate an intra-operative near infrared fluorescence imaging (NIRF) system (Frangioni laboratory) for identifying sentinel lymph nodes draining InvTCC. NIRF imaging was used to map lymph node drainage from specific quadrants of the urinary bladder in normal dogs and pigs, and to map lymph node drainage from naturally-occurring InvTCC in pet dogs where the disease closely mimics the human condition. Briefly, during surgery NIR fluorophores (human serum albumen-fluorophore complex, or quantum dots) were injected directly into the bladder wall, and fluorescence observed in lymphatics and regional nodes. Conditions studied to optimize the procedure including: type of fluorophore, depth of injection, volume of fluorophore injected, and degree of bladder distention at the time of injection. Optimal imaging occurred with very superficial injection of the fluorophore in the serosal surface of the moderately distended bladder. Considerable variability was noted from dog to dog in the pattern of lymph node drainage. NIR fluorescence was noted in lymph nodes with metastases in dogs with InvTCC. In conclusion, intra-operative NIRF imaging is a promising approach to improve sentinel lymph node mapping in invasive urinary bladder cancer.

  7. A stochastic model for identifying differential gene pair co-expression patterns in prostate cancer progression

    Directory of Open Access Journals (Sweden)

    Mao Yu

    2009-07-01

    Full Text Available Abstract Background The identification of gene differential co-expression patterns between cancer stages is a newly developing method to reveal the underlying molecular mechanisms of carcinogenesis. Most researches of this subject lack an algorithm useful for performing a statistical significance assessment involving cancer progression. Lacking this specific algorithm is apparently absent in identifying precise gene pairs correlating to cancer progression. Results In this investigation we studied gene pair co-expression change by using a stochastic process model for approximating the underlying dynamic procedure of the co-expression change during cancer progression. Also, we presented a novel analytical method named 'Stochastic process model for Identifying differentially co-expressed Gene pair' (SIG method. This method has been applied to two well known prostate cancer data sets: hormone sensitive versus hormone resistant, and healthy versus cancerous. From these data sets, 428,582 gene pairs and 303,992 gene pairs were identified respectively. Afterwards, we used two different current statistical methods to the same data sets, which were developed to identify gene pair differential co-expression and did not consider cancer progression in algorithm. We then compared these results from three different perspectives: progression analysis, gene pair identification effectiveness analysis, and pathway enrichment analysis. Statistical methods were used to quantify the quality and performance of these different perspectives. They included: Re-identification Scale (RS and Progression Score (PS in progression analysis, True Positive Rate (TPR in gene pair analysis, and Pathway Enrichment Score (PES in pathway analysis. Our results show small values of RS and large values of PS, TPR, and PES; thus, suggesting that gene pairs identified by the SIG method are highly correlated with cancer progression, and highly enriched in disease-specific pathways. From

  8. Global tyrosine kinome profiling of human thyroid tumors identifies Src as a promising target for invasive cancers

    International Nuclear Information System (INIS)

    Cho, Nancy L.; Lin, Chi-Iou; Du, Jinyan; Whang, Edward E.; Ito, Hiromichi; Moore, Francis D.; Ruan, Daniel T.

    2012-01-01

    Highlights: ► Kinome profiling is a novel technique for identifying activated kinases in human cancers. ► Src activity is increased in invasive thyroid cancers. ► Inhibition of Src activity decreased proliferation and invasion in vitro. ► Further investigation of Src targeted therapies in thyroid cancer is warranted. -- Abstract: Background: Novel therapies are needed for the treatment of invasive thyroid cancers. Aberrant activation of tyrosine kinases plays an important role in thyroid oncogenesis. Because current targeted therapies are biased toward a small subset of tyrosine kinases, we conducted a study to reveal novel therapeutic targets for thyroid cancer using a bead-based, high-throughput system. Methods: Thyroid tumors and matched normal tissues were harvested from twenty-six patients in the operating room. Protein lysates were analyzed using the Luminex immunosandwich, a bead-based kinase phosphorylation assay. Data was analyzed using GenePattern 3.0 software and clustered according to histology, demographic factors, and tumor status regarding capsular invasion, size, lymphovascular invasion, and extrathyroidal extension. Survival and invasion assays were performed to determine the effect of Src inhibition in papillary thyroid cancer (PTC) cells. Results: Tyrosine kinome profiling demonstrated upregulation of nine tyrosine kinases in tumors relative to matched normal thyroid tissue: EGFR, PTK6, BTK, HCK, ABL1, TNK1, GRB2, ERK, and SRC. Supervised clustering of well-differentiated tumors by histology, gender, age, or size did not reveal significant differences in tyrosine kinase activity. However, supervised clustering by the presence of invasive disease showed increased Src activity in invasive tumors relative to non-invasive tumors (60% v. 0%, p < 0.05). In vitro, we found that Src inhibition in PTC cells decreased cell invasion and proliferation. Conclusion: Global kinome analysis enables the discovery of novel targets for thyroid cancer

  9. Assessing tumor progression factors by somatic gene transfer into a mouse model: Bcl-xL promotes islet tumor cell invasion.

    Directory of Open Access Journals (Sweden)

    Yi-Chieh Nancy Du

    2007-10-01

    Full Text Available Tumors develop through multiple stages, implicating multiple effectors, but the tools to assess how candidate genes contribute to stepwise tumor progression have been limited. We have developed a novel system in which progression of phenotypes in a mouse model of pancreatic islet cell tumorigenesis can be used to measure the effects of genes introduced by cell-type-specific infection with retroviral vectors. In this system, bitransgenic mice, in which the rat insulin promoter (RIP drives expression of both the SV40 T antigen (RIP-Tag and the receptor for subgroup A avian leukosis virus (RIP-tva, are infected with avian viral vectors carrying cDNAs encoding candidate progression factors. Like RIP-Tag mice, RIP-Tag; RIP-tva bitransgenic mice develop isolated carcinomas by approximately 14 wk of age, after progression through well-defined stages that are similar to aspects of human tumor progression, including hyperplasia, angiogenesis, adenoma, and invasive carcinoma. When avian retroviral vectors carrying a green fluorescent protein marker were introduced into RIP-Tag; RIP-tva mice by intra-cardiac injection at the hyperplastic or early dysplastic stage of tumorigenesis, approximately 20% of the TVA-positive cells were infected and expressed green fluorescent proteins as measured by flow cytometry. Similar infection with vectors carrying cDNA encoding either of two progression factors, a dominant-negative version of cadherin 1 (dnE-cad or Bcl-xL, accelerated the formation of islet tumors with invasive properties and pancreatic lymph node metastasis. To begin studying the mechanism by which Bcl-xL, an anti-apoptotic protein, promotes invasion and metastasis, RIP-Tag; RIP-tva pancreatic islet tumor cells were infected in vitro with RCASBP-Bcl-xL. Although no changes were observed in rates of proliferation or apoptosis, Bcl-xL altered cell morphology, remodeled the actin cytoskeleton, and down-regulated cadherin 1; it also induced cell migration and

  10. A novel mouse model identifies cooperating mutations and therapeutic targets critical for chronic myeloid leukemia progression

    Science.gov (United States)

    Giotopoulos, George; van der Weyden, Louise; Osaki, Hikari; Rust, Alistair G.; Gallipoli, Paolo; Meduri, Eshwar; Horton, Sarah J.; Chan, Wai-In; Foster, Donna; Prinjha, Rab K.; Pimanda, John E.; Tenen, Daniel G.; Vassiliou, George S.; Koschmieder, Steffen; Adams, David J.

    2015-01-01

    The introduction of highly selective ABL-tyrosine kinase inhibitors (TKIs) has revolutionized therapy for chronic myeloid leukemia (CML). However, TKIs are only efficacious in the chronic phase of the disease and effective therapies for TKI-refractory CML, or after progression to blast crisis (BC), are lacking. Whereas the chronic phase of CML is dependent on BCR-ABL, additional mutations are required for progression to BC. However, the identity of these mutations and the pathways they affect are poorly understood, hampering our ability to identify therapeutic targets and improve outcomes. Here, we describe a novel mouse model that allows identification of mechanisms of BC progression in an unbiased and tractable manner, using transposon-based insertional mutagenesis on the background of chronic phase CML. Our BC model is the first to faithfully recapitulate the phenotype, cellular and molecular biology of human CML progression. We report a heterogeneous and unique pattern of insertions identifying known and novel candidate genes and demonstrate that these pathways drive disease progression and provide potential targets for novel therapeutic strategies. Our model greatly informs the biology of CML progression and provides a potent resource for the development of candidate therapies to improve the dismal outcomes in this highly aggressive disease. PMID:26304963

  11. Human renal adipose tissue induces the invasion and progression of renal cell carcinoma

    Science.gov (United States)

    Campo-Verde-Arbocco, Fiorella; López-Laur, José D.; Romeo, Leonardo R.; Giorlando, Noelia; Bruna, Flavia A.; Contador, David E.; López-Fontana, Gastón; Santiano, Flavia E.; Sasso, Corina V.; Zyla, Leila E.; López-Fontana, Constanza M.; Calvo, Juan C.; Carón, Rubén W.; Creydt, Virginia Pistone

    2017-01-01

    We evaluated the effects of conditioned media (CMs) of human adipose tissue from renal cell carcinoma located near the tumor (hRATnT) or farther away from the tumor (hRATfT), on proliferation, adhesion and migration of tumor (786-O and ACHN) and non-tumor (HK-2) human renal epithelial cell lines. Human adipose tissues were obtained from patients with renal cell carcinoma (RCC) and CMs from hRATnT and hRATfT incubation. Proliferation, adhesion and migration were quantified in 786-O, ACHN and HK-2 cell lines incubated with hRATnT-, hRATfT- or control-CMs. We evaluated versican, adiponectin and leptin expression in CMs from hRATnT and hRATfT. We evaluated AdipoR1/2, ObR, pERK, pAkt y pPI3K expression on cell lines incubated with CMs. No differences in proliferation of cell lines was found after 24 h of treatment with CMs. All cell lines showed a significant decrease in cell adhesion and increase in cell migration after incubation with hRATnT-CMs vs. hRATfT- or control-CMs. hRATnT-CMs showed increased levels of versican and leptin, compared to hRATfT-CMs. AdipoR2 in 786-O and ACHN cells decreased significantly after incubation with hRATfT- and hRATnT-CMs vs. control-CMs. We observed a decrease in the expression of pAkt in HK-2, 786-O and ACHN incubated with hRATnT-CMs. This result could partially explain the observed changes in migration and cell adhesion. We conclude that hRATnT released factors, such as leptin and versican, could enhance the invasive potential of renal epithelial cell lines and could modulate the progression of the disease. PMID:29212223

  12. Inherent phenotypic plasticity facilitates progression of head and neck cancer: Endotheliod characteristics enable angiogenesis and invasion

    Energy Technology Data Exchange (ETDEWEB)

    Tong, Meng, E-mail: tong.59@osu.edu [Division of Oral Pathology and Radiology, The Ohio State University College of Dentistry, Columbus, OH 43210 (United States); Han, Byungdo B.; Holpuch, Andrew S.; Pei, Ping; He, Lingli; Mallery, Susan R. [Division of Oral Pathology and Radiology, The Ohio State University College of Dentistry, Columbus, OH 43210 (United States)

    2013-04-15

    The presence of the EMT (epithelial-mesenchymal transition), EndMT (endothelial-mesenchymal transition) and VM (vasculogenic mimicry) demonstrates the multidirectional extent of phenotypic plasticity in cancers. Previous findings demonstrating the crosstalk between head and neck squamous cell carcinoma (HNSCC) and vascular endothelial growth factor (VEGF) imply that HNSCC cells share some functional commonalities with endothelial cells. Our current results reveal that cultured HNSCC cells not only possess endothelial-specific markers, but also display endotheliod functional features including low density lipoprotein uptake, formation of tube-like structures on Matrigel and growth state responsiveness to VEGF and endostatin. HNSCC cell subpopulations are also highly responsive to transforming growth factor-β1 and express its auxiliary receptor, endoglin. Furthermore, the endotheliod characteristics observed in vitro recapitulate phenotypic features observed in human HNSCC tumors. Conversely, cultured normal human oral keratinocytes and intact or ulcerated human oral epithelia do not express comparable endotheliod characteristics, which imply that assumption of endotheliod features is restricted to transformed keratinocytes. In addition, this phenotypic state reciprocity facilitates HNSCC progression by increasing production of factors that are concurrently pro-proliferative and pro-angiogenic, conserving cell energy stores by LDL internalization and enhancing cell mobility. Finally, recognition of this endotheliod phenotypic transition provides a solid rationale to evaluate the antitumorigenic potential of therapeutic agents formerly regarded as exclusively angiostatic in scope. - Highlights: ► HNSCC tumor cells express endothelial specific markers VE-cadherin, CD31 and vimentin. ► Similarly, cultured HNSCC cells retain expression of these markers. ► HNSCC cells demonstrate functional endotheliod characteristics i.e. AcLDL uptake. ► HNSCC cell

  13. Three-dimensional modelling identifies novel genetic dependencies associated with breast cancer progression in the isogenic MCF10 model

    OpenAIRE

    Maguire, Sarah L.; Peck, Barrie; Wai, Patty T.; Campbell, James; Barker, Holly; Gulati, Aditi; Daley, Frances; Vyse, Simon; Huang, Paul; Lord, Christopher J.; Farnie, Gillian; Brennan, Keith; Natrajan, Rachael

    2016-01-01

    Abstract The initiation and progression of breast cancer from the transformation of the normal epithelium to ductal carcinoma in situ (DCIS) and invasive disease is a complex process involving the acquisition of genetic alterations and changes in gene expression, alongside microenvironmental and recognized histological alterations. Here, we sought to comprehensively characterise the genomic and transcriptomic features of the MCF10 isogenic model of breast cancer progression, and to functional...

  14. A new approach to horizon-scanning: identifying potentially invasive alien species and their introduction pathways

    NARCIS (Netherlands)

    Matthews, Jonathan; Beringen, Ruud; Creemers, Raymond; Hollander, Hans; van Kessel, Nils; van Kleef, Hein; de Koppel, Sander van; Lemaire, Adrienne J. J.; Ode, Baudewijn; Verbrugge, Laura N. H.; Hendriks, A. Jan; Schipper, Aafke M.; van der Velde, Gerard; Leuven, Rob S. E. W.

    Invasive alien species (IAS) are considered an important threat to global biodiversity due to major ecological impacts. In 2014, the European Union (EU) introduced a regulation (EU) No 1143/2014 on the prevention and management of the introduction and spread of IAS. The first risk prioritized list

  15. Lugol's iodine identifies synchronous invasive carcinoma--time for a clinical trial.

    Science.gov (United States)

    Kanatas, A N; Jenkins, G W; Sutton, D; McCaul, J A

    2011-07-01

    Lugol's iodine is currently under investigation as a technique to detect dysplasia, carcinoma in situ and invasive carcinoma at resection margins, plus further afield. Lugol's iodine is inexpensive and easy to use. We present two cases where the technique revealed abnormal mucosa (one carcinoma, one squamous cell carcinoma in situ) at distant sites from the tumour being treated within oral cavity and oropharynx. Copyright © 2010 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  16. Huntington's disease biomarker progression profile identified by transcriptome sequencing in peripheral blood.

    Science.gov (United States)

    Mastrokolias, Anastasios; Ariyurek, Yavuz; Goeman, Jelle J; van Duijn, Erik; Roos, Raymund A C; van der Mast, Roos C; van Ommen, GertJan B; den Dunnen, Johan T; 't Hoen, Peter A C; van Roon-Mom, Willeke M C

    2015-10-01

    With several therapeutic approaches in development for Huntington's disease, there is a need for easily accessible biomarkers to monitor disease progression and therapy response. We performed next-generation sequencing-based transcriptome analysis of total RNA from peripheral blood of 91 mutation carriers (27 presymptomatic and, 64 symptomatic) and 33 controls. Transcriptome analysis by DeepSAGE identified 167 genes significantly associated with clinical total motor score in Huntington's disease patients. Relative to previous studies, this yielded novel genes and confirmed previously identified genes, such as H2AFY, an overlap in results that has proven difficult in the past. Pathway analysis showed enrichment of genes of the immune system and target genes of miRNAs, which are downregulated in Huntington's disease models. Using a highly parallelized microfluidics array chip (Fluidigm), we validated 12 of the top 20 significant genes in our discovery cohort and 7 in a second independent cohort. The five genes (PROK2, ZNF238, AQP9, CYSTM1 and ANXA3) that were validated independently in both cohorts present a candidate biomarker panel for stage determination and therapeutic readout in Huntington's disease. Finally we suggest a first empiric formula predicting total motor score from the expression levels of our biomarker panel. Our data support the view that peripheral blood is a useful source to identify biomarkers for Huntington's disease and monitor disease progression in future clinical trials.

  17. Risk estimation of multiple recurrence and progression of non muscle invasive bladder carcinoma using new mathematical models.

    Science.gov (United States)

    Luján, S; Santamaría, C; Pontones, J L; Ruiz-Cerdá, J L; Trassierra, M; Vera-Donoso, C D; Solsona, E; Jiménez-Cruz, F

    2014-12-01

    To apply new mathematical models according to Non Muscle Invasive Bladder Carcinoma (NMIBC) biological characteristics and enabling an accurate risk estimation of multiple recurrences and tumor progression. The classical Cox model is not valid for the assessment of this kind of events becausethe time betweenrecurrencesin the same patientmay be stronglycorrelated. These new models for risk estimation of recurrence/progression lead to individualized monitoring and treatment plan. 960 patients with primary NMIBC were enrolled. The median follow-up was 48.1 (3-160) months. Results obtained were validated in 240 patients from other center. Transurethral resection of the bladder (TURB) and random bladder biopsy were performed. Subsequently, adjuvant localized chemotherapy was performed. The variables analyzed were: number and tumor size, age, chemotherapy and histopathology. The endpoints were time to recurrence and time to progression. Cox model and its extensions were used as joint frailty model for multiple recurrence and progression. Model accuracy was calculated using Harrell's concordance index (c-index). 468 (48.8%) patients developed at least one tumor recurrence and tumor progression was reported in 52 (5.4%) patients. Variables for multiple-recurrence risk are: age, grade, number, size, treatment and the number of prior recurrences. All these together with age, stage and grade are the variables for progression risk. Concordance index was 0.64 and 0.85 for multiple recurrence and progression respectively. the high concordance reported besides to the validation process in external source, allow accurate multi-recurrence/progression risk estimation. As consequence, it is possible to schedule a follow-up and treatment individualized plan in new and recurrent NMCB cases. Copyright © 2014 AEU. Published by Elsevier Espana. All rights reserved.

  18. MMP19 is upregulated during melanoma progression and increases invasion of melanoma cells

    Czech Academy of Sciences Publication Activity Database

    Muller, M.; Beck, Inken; Gadesmann, J.; Karschuk, N.; Paschen, A.; Proksch, E.; Djonov, V.; Reiss, K.; Sedláček, Radislav

    2010-01-01

    Roč. 23, č. 4 (2010), s. 511-521 ISSN 0893-3952 Institutional research plan: CEZ:AV0Z50520514 Keywords : melanoma * invasion * matrix metalloproteinase Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.176, year: 2010

  19. New Approaches for Early Detection of Breast Tumor Invasion or Progression

    Science.gov (United States)

    2003-05-01

    IMMUNOHISTOCHEMICAL ASSESSMENT OF \\ Breast Disease PRIMARY LESIONS OF BREAST EPITHELIAL February 13-16, 2003 INVASION INTO BLOOD VESSELS Ritz - Carlton , Amelia...myoepithelial cell lineages: A new cell biological concept . Lab Invest 2002;82(6):737-46. 2. Tavassoli FA. Pathology of the Breast, 2nd edn. Hong Kong: McGraw

  20. Tumor Microenvironment and Progression to Invasion after a Diagnosis of Ductal Carcinoma In Situ

    Science.gov (United States)

    2013-11-01

    contraceptive use and risk of breast carcinoma in situ. Cancer Epidemiol Biomarkers Prev 16(11):2262–2268 16. Sprague BL, Trentham-Dietz A, Nichols HB...in situ (DCIS) makes up 18% of all new breast cancer diagnoses, and is considered a precursor to invasive breast cancer even though the majority of...breast to evaluate syndecan-1 expression and collagen alignment. These DCIS cases, diagnosed between 1995 and 1999, have been followed for breast cancer

  1. An iPSC Line from Human Pancreatic Ductal Adenocarcinoma Undergoes Early to Invasive Stages of Pancreatic Cancer Progression

    Directory of Open Access Journals (Sweden)

    Jungsun Kim

    2013-06-01

    Full Text Available Pancreatic ductal adenocarcinoma (PDAC carries a dismal prognosis and lacks a human cell model of early disease progression. When human PDAC cells are injected into immunodeficient mice, they generate advanced-stage cancer. We hypothesized that if human PDAC cells were converted to pluripotency and then allowed to differentiate back into pancreatic tissue, they might undergo early stages of cancer. Although most induced pluripotent stem cell (iPSC lines were not of the expected cancer genotype, one PDAC line, 10–22 cells, when injected into immunodeficient mice, generated pancreatic intraepithelial neoplasia (PanIN precursors to PDAC that progressed to the invasive stage. The PanIN-like cells secrete or release proteins from many genes that are known to be expressed in human pancreatic cancer progression and that predicted an HNF4α network in intermediate-stage lesions. Thus, rare events allow iPSC technology to provide a live human cell model of early pancreatic cancer and insights into disease progression.

  2. Count your eggs before they invade: identifying and quantifying egg clutches of two invasive apple snail species (Pomacea).

    Science.gov (United States)

    Kyle, Colin H; Plantz, Allyson L; Shelton, Therese; Burks, Romi L

    2013-01-01

    Winning the war against invasive species requires early detection of invasions. Compared to terrestrial invaders, aquatic species often thrive undetected under water and do not garner notice until too late for early action. However, fortunately for managers, apple snails (Family Ampullariidae, Genus Pomacea) provide their own conspicuous sign of invasion in the form of vibrantly colored egg clutches. Managers can potentially use egg clutches laid in the riparian zone as a means of early detection and species identification. To facilitate such efforts, we quantified differences in characteristics (length, width, depth, mass, egg number) of field-laid clutches for the two most common invasive species of apple snail, P. canaliculata and P. maculata, in native and non-native populations. Pomacea canaliculata native and non-native populations differed noticeably only in width. Native P. maculata clutches possessed significantly greater width, mass and eggs numbers compared with native P. canaliculata. Non-native P. maculata clutches significantly exceeded all other populations in all measured characteristics. Consequently, these traits may successfully distinguish between species. Fecundity data also allowed us to develop models that accurately estimated the number of eggs per clutch for each species based on clutch dimensions. We tested one, two and three dimensional models of clutches, including rendering a clutch as either a complete ellipsoid or an ellipsoid intersected by a cylinder to represent the oviposition site. Model comparisons found the product of length and depth, with a different function for each population, best predicted egg number for both species. Comparisons of egg number to clutch volume and mass implied non-native P. canaliculata may be food limited, while non-native P. maculata appeared to produce such enormous clutches by having access to greater nutrients than the native population. With these new tools, researchers and managers can quickly

  3. Count your eggs before they invade: identifying and quantifying egg clutches of two invasive apple snail species (Pomacea.

    Directory of Open Access Journals (Sweden)

    Colin H Kyle

    Full Text Available Winning the war against invasive species requires early detection of invasions. Compared to terrestrial invaders, aquatic species often thrive undetected under water and do not garner notice until too late for early action. However, fortunately for managers, apple snails (Family Ampullariidae, Genus Pomacea provide their own conspicuous sign of invasion in the form of vibrantly colored egg clutches. Managers can potentially use egg clutches laid in the riparian zone as a means of early detection and species identification. To facilitate such efforts, we quantified differences in characteristics (length, width, depth, mass, egg number of field-laid clutches for the two most common invasive species of apple snail, P. canaliculata and P. maculata, in native and non-native populations. Pomacea canaliculata native and non-native populations differed noticeably only in width. Native P. maculata clutches possessed significantly greater width, mass and eggs numbers compared with native P. canaliculata. Non-native P. maculata clutches significantly exceeded all other populations in all measured characteristics. Consequently, these traits may successfully distinguish between species. Fecundity data also allowed us to develop models that accurately estimated the number of eggs per clutch for each species based on clutch dimensions. We tested one, two and three dimensional models of clutches, including rendering a clutch as either a complete ellipsoid or an ellipsoid intersected by a cylinder to represent the oviposition site. Model comparisons found the product of length and depth, with a different function for each population, best predicted egg number for both species. Comparisons of egg number to clutch volume and mass implied non-native P. canaliculata may be food limited, while non-native P. maculata appeared to produce such enormous clutches by having access to greater nutrients than the native population. With these new tools, researchers and

  4. Integrative genomics identifies molecular alterations that challenge the linear model of melanoma progression

    Science.gov (United States)

    Rose, Amy E.; Poliseno, Laura; Wang, Jinhua; Clark, Michael; Pearlman, Alexander; Wang, Guimin; Vega y Saenz de Miera, Eleazar C.; Medicherla, Ratna; Christos, Paul J.; Shapiro, Richard; Pavlick, Anna; Darvishian, Farbod; Zavadil, Jiri; Polsky, David; Hernando, Eva; Ostrer, Harry; Osman, Iman

    2011-01-01

    Superficial spreading melanoma (SSM) and nodular melanoma (NM) are believed to represent sequential phases of linear progression from radial to vertical growth. Several lines of clinical, pathological and epidemiologic evidence suggest, however, that SSM and NM might be the result of independent pathways of tumor development. We utilized an integrative genomic approach that combines single nucleotide polymorphism array (SNP 6.0, Affymetrix) with gene expression array (U133A 2.0, Affymetrix) to examine molecular differences between SSM and NM. Pathway analysis of the most differentially expressed genes between SSM and NM (N=114) revealed significant differences related to metabolic processes. We identified 8 genes (DIS3, FGFR1OP, G3BP2, GALNT7, MTAP, SEC23IP, USO1, ZNF668) in which NM/SSM-specific copy number alterations correlated with differential gene expression (Pmelanoma. In addition, we show that the decreased ALDH7A1 expression in SSM may be the result of epigenetic modifications. Our data reveal recurrent genomic deletions in SSM not present in NM, which challenge the linear model of melanoma progression. Furthermore, our data suggest a role for altered regulation of metabolism-related genes as a possible cause of the different clinical behavior of SSM and NM. PMID:21343389

  5. Computed Tomography Fractional Flow Reserve Can Identify Culprit Lesions in Aortoiliac Occlusive Disease Using Minimally Invasive Techniques.

    Science.gov (United States)

    Ward, Erin P; Shiavazzi, Daniele; Sood, Divya; Marsden, Allison; Lane, John; Owens, Erik; Barleben, Andrew

    2017-01-01

    Currently, the gold standard diagnostic examination for significant aortoiliac lesions is angiography. Fractional flow reserve (FFR) has a growing body of literature in coronary artery disease as a minimally invasive diagnostic procedure. Improvements in numerical hemodynamics have allowed for an accurate and minimally invasive approach to estimating FFR, utilizing cross-sectional imaging. We aim to demonstrate a similar approach to aortoiliac occlusive disease (AIOD). A retrospective review evaluated 7 patients with claudication and cross-sectional imaging showing AIOD. FFR was subsequently measured during conventional angiogram with pull-back pressures in a retrograde fashion. To estimate computed tomography (CT) FFR, CT angiography (CTA) image data were analyzed using the SimVascular software suite to create a computational fluid dynamics model of the aortoiliac system. Inlet flow conditions were derived based on cardiac output, while 3-element Windkessel outlet boundary conditions were optimized to match the expected systolic and diastolic pressures, with outlet resistance distributed based on Murray's law. The data were evaluated with a Student's t-test and receiver operating characteristic curve. All patients had evidence of AIOD on CT and FFR was successfully measured during angiography. The modeled data were found to have high sensitivity and specificity between the measured and CT FFR (P = 0.986, area under the curve = 1). The average difference between the measured and calculated FFRs was 0.136, with a range from 0.03 to 0.30. CT FFR successfully identified aortoiliac lesions with significant pressure drops that were identified with angiographically measured FFR. CT FFR has the potential to provide a minimally invasive approach to identify flow-limiting stenosis for AIOD. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Surgical staging identified false HPV-negative cases in a large series of invasive cervical cancers.

    Science.gov (United States)

    Petry, Karl Ulrich; Liebrich, Clemens; Luyten, Alexander; Zander, Martina; Iftner, Thomas

    2017-12-01

    We examined a large series of biopsy-proven invasive cervical cancers with surgical staging and HPV re-testing to estimate the relevance of HPV-negative cervical cancers in a Caucasian population. We prospectively collected smears from 371 patients with a biopsy-proven diagnosis of cervical cancer for HC2 testing of high-risk HPV (HR-HPV). In HC2-negative cases, smears and paraffin embedded tissue blocks underwent additional HPV genotyping. HC2 tests showed 31/371 cases (8.8%) had negative findings. Surgical staging showed that 21/31 HC2-negative cases (68%) were not cervical cancer. Overall, 340/350 cases of primary cervical cancer confirmed by surgical staging tested HC2 positive (97.2%). Non-high-risk HPV subtypes were detected in five cases (one HPV-53, one HPV-70, and three HPV-73) and high-risk subtypes in four patients with HC2-negative cervical cancer (two HPV 16 and two HPV-18). The remaining case, a primary undifferentiated carcinoma of the uterine cervix, tested negative for HPV-DNA with all tests. The main explanation for HPV-negative cervical cancer was a false diagnosis, followed by cancers associated with non-HR-HPV types, and false-negative HR-HPV results. Truly HPV negative seem to be very rare in Caucasian populations. Retrospective analyses without surgical staging may overestimate the proportion of HPV negative cervical cancers. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  7. Failure of Invasive Airway Placement on the First Attempt Is Associated With Progression to Cardiac Arrest in Pediatric Acute Respiratory Compromise.

    Science.gov (United States)

    Stinson, Hannah R; Srinivasan, Vijay; Topjian, Alexis A; Sutton, Robert M; Nadkarni, Vinay M; Berg, Robert A; Raymond, Tia T

    2018-01-01

    The aim of this study was to describe the proportion of acute respiratory compromise events in hospitalized pediatric patients progressing to cardiopulmonary arrest, and the clinical factors associated with progression of acute respiratory compromise to cardiopulmonary arrest. We hypothesized that failure of invasive airway placement on the first attempt (defined as multiple attempts at tracheal intubation, and/or laryngeal mask airway placement, and/or the creation of a new tracheostomy or cricothyrotomy) is independently associated with progression of acute respiratory compromise to cardiopulmonary arrest. Multicenter, international registry of pediatric in-hospital acute respiratory compromise. American Heart Association's Get with the Guidelines-Resuscitation registry (2000-2014). Children younger than 18 years with an index (first) acute respiratory compromise event. None. Of the 2,210 index acute respiratory compromise events, 64% required controlled ventilation, 26% had return of spontaneous ventilation, and 10% progressed to cardiopulmonary arrest. There were 762 acute respiratory compromise events (34%) that did not require an invasive airway, 1,185 acute respiratory compromise events (54%) with successful invasive airway placement on the first attempt, and 263 acute respiratory compromise events (12%) with failure of invasive airway placement on the first attempt. After adjusting for confounding variables, failure of invasive airway placement on the first attempt was independently associated with progression of acute respiratory compromise to cardiopulmonary arrest (adjusted odds ratio 1.8 [95% CIs, 1.2-2.6]). More than 1 in 10 hospitalized pediatric patients who experienced an acute respiratory compromise event progressed to cardiopulmonary arrest. Failure of invasive airway placement on the first attempt is independently associated with progression of acute respiratory compromise to cardiopulmonary arrest.

  8. Generalizability of the Disease State Index Prediction Model for Identifying Patients Progressing from Mild Cognitive Impairment to Alzheimer's Disease

    NARCIS (Netherlands)

    Hall, A.; Munoz-Ruiz, M.; Mattila, J.; Koikkalainen, J.; Tsolaki, M.; Mecocci, P.; Kloszewska, I.; Vellas, B.; Lovestone, S.; Visser, P.J.; Lotjonen, J.; Soininen, H.

    2015-01-01

    Background: The Disease State Index (DSI) prediction model measures the similarity of patient data to diagnosed stable and progressive mild cognitive impairment (MCI) cases to identify patients who are progressing to Alzheimer's disease. Objectives: We evaluated how well the DSI generalizes across

  9. Integration of genomic, transcriptomic and proteomic data identifies two biologically distinct subtypes of invasive lobular breast cancer.

    Science.gov (United States)

    Michaut, Magali; Chin, Suet-Feung; Majewski, Ian; Severson, Tesa M; Bismeijer, Tycho; de Koning, Leanne; Peeters, Justine K; Schouten, Philip C; Rueda, Oscar M; Bosma, Astrid J; Tarrant, Finbarr; Fan, Yue; He, Beilei; Xue, Zheng; Mittempergher, Lorenza; Kluin, Roelof J C; Heijmans, Jeroen; Snel, Mireille; Pereira, Bernard; Schlicker, Andreas; Provenzano, Elena; Ali, Hamid Raza; Gaber, Alexander; O'Hurley, Gillian; Lehn, Sophie; Muris, Jettie J F; Wesseling, Jelle; Kay, Elaine; Sammut, Stephen John; Bardwell, Helen A; Barbet, Aurélie S; Bard, Floriane; Lecerf, Caroline; O'Connor, Darran P; Vis, Daniël J; Benes, Cyril H; McDermott, Ultan; Garnett, Mathew J; Simon, Iris M; Jirström, Karin; Dubois, Thierry; Linn, Sabine C; Gallagher, William M; Wessels, Lodewyk F A; Caldas, Carlos; Bernards, Rene

    2016-01-05

    Invasive lobular carcinoma (ILC) is the second most frequently occurring histological breast cancer subtype after invasive ductal carcinoma (IDC), accounting for around 10% of all breast cancers. The molecular processes that drive the development of ILC are still largely unknown. We have performed a comprehensive genomic, transcriptomic and proteomic analysis of a large ILC patient cohort and present here an integrated molecular portrait of ILC. Mutations in CDH1 and in the PI3K pathway are the most frequent molecular alterations in ILC. We identified two main subtypes of ILCs: (i) an immune related subtype with mRNA up-regulation of PD-L1, PD-1 and CTLA-4 and greater sensitivity to DNA-damaging agents in representative cell line models; (ii) a hormone related subtype, associated with Epithelial to Mesenchymal Transition (EMT), and gain of chromosomes 1q and 8q and loss of chromosome 11q. Using the somatic mutation rate and eIF4B protein level, we identified three groups with different clinical outcomes, including a group with extremely good prognosis. We provide a comprehensive overview of the molecular alterations driving ILC and have explored links with therapy response. This molecular characterization may help to tailor treatment of ILC through the application of specific targeted, chemo- and/or immune-therapies.

  10. Non-invasive Carotid Artery Imaging to Identify the Vulnerable Plaque: Current Status and Future Goals.

    Science.gov (United States)

    Huibers, A; de Borst, G J; Wan, S; Kennedy, F; Giannopoulos, A; Moll, F L; Richards, T

    2015-11-01

    The current clinical practise to determine if a patient should undergo carotid intervention to prevent stroke is to determine the clinical features combined with degree of carotid stenosis. However, this does not accurately determine the individual patient's risk for future stroke. A thin fibrous cap, a large lipid core, high macrophage count, and intraplaque haemorrhage have all been identified as markers of the so-called "vulnerable" plaque being related to a higher stroke risk. There is a need to assess the accuracy of in vivo imaging to identify vulnerable plaque characteristics, thereby enabling in vivo risk stratification to guide clinical decision-making. The aim of this topical review is to assess the roles of currently available imaging modalities that are applied in clinical practice and those experimental techniques that are close to clinical translation in defining carotid plaque characteristics and in informing clinical practice. Ultrasound is a low cost and ready available low-risk tool, but it lacks the accuracy to reliably detect individual plaque components and characteristics. Computed tomography is considered to be the best imaging technique to identify calcification in the carotid plaque. Magnetic resonance imaging (MRI) can identify most described plaque characteristics with moderate to good agreement. Positron emission tomography allows assessment of specific metabolic functions with tracers labelled with positron emitting radio-isotopes, but limited spatial resolution makes anatomic precision imprecise. MRI has demonstrated the most potential, with good sensitivity and specificity for most plaque characteristics. However, currently there is no single imaging modality that can reliably identify the vulnerable plaque in relation to development of future stroke. Copyright © 2015 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

  11. Selection and evolution in the genomic landscape of copy number alterations in ductal carcinoma in situ (DCIS) and its progression to invasive carcinoma of ductal/no special type: a meta-analysis.

    Science.gov (United States)

    Rane, Swapnil Ulhas; Mirza, Hasan; Grigoriadis, Anita; Pinder, Sarah E

    2015-08-01

    Ductal carcinoma in situ (DCIS) is a pre-invasive malignancy detected with an increasing frequency through screening mammography. One of the primary aims of therapy is to prevent local recurrence, as in situ or as invasive carcinoma, the latter arising in half of the recurrent cases. Reliable biomarkers predictive of its association with recurrence, particularly as invasive disease, are however lacking. In this study, we perform a meta-analysis of 26 studies which report somatic copy number aberrations (SCNAs) in 288 cases of 'pure' DCIS and 328 of DCIS associated with invasive carcinoma, along with additional unmatched cases of 145 invasive carcinoma of ductal/no special type (IDC) and 50 of atypical ductal hyperplasia (ADH). SCNA frequencies across the genome were calculated at cytoband resolution (UCSC genome build 19) to maximally utilize the available information in published literature. Fisher's exact test was used to identify significant differences in the gain-loss distribution in each cytoband in different group comparisons. We found synchronous DCIS to be at a more advanced stage of genetic aberrations than pure DCIS and was very similar to IDC. Differences in gains and losses in each disease process (i.e. invasive or in situ) at each cytoband were used to infer evidence of selection and conservation for each cytoband and to define an evolutionary conservation scale (ECS) as a tool to identify and distinguish driver SCNA from the passenger SCNA. Using ECS, we have identified aberrations that show evidence of selection from the early stages of neoplasia (i.e. in ADH and pure DCIS) and persist in IDC; we postulate these to be driver aberrations and that their presence may predict progression to invasive disease.

  12. Quantitative in vivo Analyses Reveal Calcium-dependent Phosphorylation Sites and Identifies a Novel Component of the Toxoplasma Invasion Motor Complex

    Science.gov (United States)

    Nebl, Thomas; Prieto, Judith Helena; Kapp, Eugene; Smith, Brian J.; Williams, Melanie J.; Yates, John R.; Cowman, Alan F.; Tonkin, Christopher J.

    2011-01-01

    Apicomplexan parasites depend on the invasion of host cells for survival and proliferation. Calcium-dependent signaling pathways appear to be essential for micronemal release and gliding motility, yet the target of activated kinases remains largely unknown. We have characterized calcium-dependent phosphorylation events during Toxoplasma host cell invasion. Stimulation of live tachyzoites with Ca2+-mobilizing drugs leads to phosphorylation of numerous parasite proteins, as shown by differential 2-DE display of 32[P]-labeled protein extracts. Multi-dimensional Protein Identification Technology (MudPIT) identified ∼546 phosphorylation sites on over 300 Toxoplasma proteins, including 10 sites on the actomyosin invasion motor. Using a Stable Isotope of Amino Acids in Culture (SILAC)-based quantitative LC-MS/MS analyses we monitored changes in the abundance and phosphorylation of the invasion motor complex and defined Ca2+-dependent phosphorylation patterns on three of its components - GAP45, MLC1 and MyoA. Furthermore, calcium-dependent phosphorylation of six residues across GAP45, MLC1 and MyoA is correlated with invasion motor activity. By analyzing proteins that appear to associate more strongly with the invasion motor upon calcium stimulation we have also identified a novel 15-kDa Calmodulin-like protein that likely represents the MyoA Essential Light Chain of the Toxoplasma invasion motor. This suggests that invasion motor activity could be regulated not only by phosphorylation but also by the direct binding of calcium ions to this new component. PMID:21980283

  13. Progress report on a fast, particle-identifying trigger based on ring-imaging Cherenkov techniques

    International Nuclear Information System (INIS)

    Carroll, J.; Igo, G.; Jacobs, P.; Matis, H.; Naudet, C.; Schroeder, L.S.; Seidl, P.A.; Hallman, T.J.

    1990-01-01

    Experiments which require a large sample of relatively rare events need an efficient (low dead time) trigger that does more than select central collisions. The authors propose to develop a trigger that will permit sophisticated multi-particle identification on a time scale appropriate for the interaction rates expected at RHIC. The visible component of the ring-image produced by an appropriate Cherenkov-radiator-mirror combination is focused onto an array of fast photo-detectors. The output of the photo-array is coupled to a fast pattern recognition system that will identify events containing particles of specified types and angular configurations. As a parallel effort, they propose to develop a spectrum-splitting mirror that will permit the ring-image from a single radiator to be used both in this trigger (the visible component of the image) and in a TMAE containing gas detector (the UV component). The gas detector will provide higher resolution information on particle ID and direction with a delay of a few microseconds. This technique will enable nearly optimal use of the information contained in the Cherenkov spectrum. The authors report progress on the three goals set forth in the proposal: 1. the development of a fast photo-array; 2. the development of a spectrum splitting mirror; and 3. the development and simulation of fast parallel algorithms for ring finding

  14. Non-invasive mapping of the gastrointestinal microbiota identifies children with inflammatory bowel disease.

    Directory of Open Access Journals (Sweden)

    Eliseo Papa

    Full Text Available Pediatric inflammatory bowel disease (IBD is challenging to diagnose because of the non-specificity of symptoms; an unequivocal diagnosis can only be made using colonoscopy, which clinicians are reluctant to recommend for children. Diagnosis of pediatric IBD is therefore frequently delayed, leading to inappropriate treatment plans and poor outcomes. We investigated the use of 16S rRNA sequencing of fecal samples and new analytical methods to assess differences in the microbiota of children with IBD and other gastrointestinal disorders.We applied synthetic learning in microbial ecology (SLiME analysis to 16S sequencing data obtained from i published surveys of microbiota diversity in IBD and ii fecal samples from 91 children and young adults who were treated in the gastroenterology program of Children's Hospital (Boston, USA. The developed method accurately distinguished control samples from those of patients with IBD; the area under the receiver-operating-characteristic curve (AUC value was 0.83 (corresponding to 80.3% sensitivity and 69.7% specificity at a set threshold. The accuracy was maintained among data sets collected by different sampling and sequencing methods. The method identified taxa associated with disease states and distinguished patients with Crohn's disease from those with ulcerative colitis with reasonable accuracy. The findings were validated using samples from an additional group of 68 patients; the validation test identified patients with IBD with an AUC value of 0.84 (e.g. 92% sensitivity, 58.5% specificity.Microbiome-based diagnostics can distinguish pediatric patients with IBD from patients with similar symptoms. Although this test can not replace endoscopy and histological examination as diagnostic tools, classification based on microbial diversity is an effective complementary technique for IBD detection in pediatric patients.

  15. Non-invasive mapping of the gastrointestinal microbiota identifies children with inflammatory bowel disease.

    Science.gov (United States)

    Papa, Eliseo; Docktor, Michael; Smillie, Christopher; Weber, Sarah; Preheim, Sarah P; Gevers, Dirk; Giannoukos, Georgia; Ciulla, Dawn; Tabbaa, Diana; Ingram, Jay; Schauer, David B; Ward, Doyle V; Korzenik, Joshua R; Xavier, Ramnik J; Bousvaros, Athos; Alm, Eric J

    2012-01-01

    Pediatric inflammatory bowel disease (IBD) is challenging to diagnose because of the non-specificity of symptoms; an unequivocal diagnosis can only be made using colonoscopy, which clinicians are reluctant to recommend for children. Diagnosis of pediatric IBD is therefore frequently delayed, leading to inappropriate treatment plans and poor outcomes. We investigated the use of 16S rRNA sequencing of fecal samples and new analytical methods to assess differences in the microbiota of children with IBD and other gastrointestinal disorders. We applied synthetic learning in microbial ecology (SLiME) analysis to 16S sequencing data obtained from i) published surveys of microbiota diversity in IBD and ii) fecal samples from 91 children and young adults who were treated in the gastroenterology program of Children's Hospital (Boston, USA). The developed method accurately distinguished control samples from those of patients with IBD; the area under the receiver-operating-characteristic curve (AUC) value was 0.83 (corresponding to 80.3% sensitivity and 69.7% specificity at a set threshold). The accuracy was maintained among data sets collected by different sampling and sequencing methods. The method identified taxa associated with disease states and distinguished patients with Crohn's disease from those with ulcerative colitis with reasonable accuracy. The findings were validated using samples from an additional group of 68 patients; the validation test identified patients with IBD with an AUC value of 0.84 (e.g. 92% sensitivity, 58.5% specificity). Microbiome-based diagnostics can distinguish pediatric patients with IBD from patients with similar symptoms. Although this test can not replace endoscopy and histological examination as diagnostic tools, classification based on microbial diversity is an effective complementary technique for IBD detection in pediatric patients.

  16. Impact of lymphovascular invasion on recurrence and progression rates in patients with pT1 urothelial carcinoma of bladder after transurethral resection

    Directory of Open Access Journals (Sweden)

    Sha N

    2015-11-01

    Full Text Available Nan Sha,* Linguo Xie,* Tao Chen,* Chen Xing, Xiaoteng Liu, Yu Zhang, Zhonghua Shen, Hao Xu, Zhouliang Wu, Hailong Hu, Changli Wu Department of Urology, Tianjin Key Laboratory of Urology, Tianjin Institute of Urology, Second Hospital of Tianjin Medical University, Tianjin, People’s Republic of China *These authors contributed equally to this work Objective: To evaluate the clinical significance of lymphovascular invasion (LVI on recurrence and progression rates in patients with pT1 urothelial carcinoma of bladder after transurethral resection.Methods: This retrospective study was performed with 155 patients with newly diagnosed pT1 urothelial carcinoma of bladder who were treated with transurethral resection of bladder tumor at our institution from January 2006 to January 2010. The presence or absence of LVI was examined by pathologists. Chi-square test was performed to identify the correlations between LVI and other clinical and pathological features. Kaplan–Meier method was used to estimate the recurrence-free survival (RFS and progression-free survival curves and difference was determined by the log-rank test. Univariate and multivariate analyses were performed to determine the predictive factors through a Cox proportional hazards analysis model.Results: LVI was detected in a total of 34 patients (21.9%. While LVI was associated with high-grade tumors (P<0.001 and intravesical therapy (P=0.009. Correlations with age (P=0.227, sex (P=0.376, tumor size (P=0.969, tumor multiplicity (P=0.196, carcinoma in situ (P=0.321, and smoking (P=0.438 were not statistically significant. There was a statistically significant tendency toward higher recurrence rate and shorter RFS time in LVI-positive patients. However, no statistically significant differences were observed in progression rate between the two groups. Moreover, multivariate Cox proportional hazards analysis revealed that LVI, tumor size, and smoking were independent prognostic predictors of

  17. Identifying barriers to effective management of widespread invasive alien trees: Prosopis species (mesquite) in South Africa as a case study

    CSIR Research Space (South Africa)

    Shackleton, RT

    2016-05-01

    Full Text Available and in some cases improve the benefits that some invasive species can provide. This study assesses the barriers that hinder the effective management of widespread tree invasions, drawing insights from a case study of invasions of Prosopis species (mesquite...

  18. Integrating molecular and ecological approaches to identify potential polymicrobial pathogens over a shrimp disease progression.

    Science.gov (United States)

    Dai, Wenfang; Yu, Weina; Xuan, Lixia; Tao, Zhen; Xiong, Jinbo

    2018-04-01

    It is now recognized that some gut diseases attribute to polymicrobial pathogens infections. Thus, traditional isolation of single pathogen from disease subjects could bias the identification of causal agents. To fill this gap, using Illumina sequencing of the bacterial 16S rRNA gene, we explored the dynamics of gut bacterial communities over a shrimp disease progression. The results showed significant differences in the gut bacterial communities between healthy and diseased shrimp. Potential pathogens were inferred by a local pathogens database, of which two OTUs (affiliated with Vibrio tubiashii and Vibrio harveyi) exhibited significantly higher abundances in diseased shrimp as compared to healthy subjects. The two OTUs cumulatively contributed 64.5% dissimilarity in the gut microbiotas between shrimp health status. Notably, the random Forest model depicted that profiles of the two OTUs contributed 78.5% predicted accuracy of shrimp health status. Removal of the two OTUs from co-occurrence networks led to network fragmentation, suggesting their gatekeeper features. For these evidences, the two OTUs were inferred as candidate pathogens. Three virulence genes (bca, tlpA, and fdeC) that were coded by the two candidate pathogens were inferred by a virulence factor database, which were enriched significantly (P < 0.05 in the three cases, as validated by qPCR) in diseased shrimp as compared to healthy ones. The two candidate pathogens were repressed by Flavobacteriaceae, Garvieae, and Photobacrerium species in healthy shrimp, while these interactions shifted into synergy in disease cohorts. Collectively, our findings offer a frame to identify potential polymicrobial pathogen infections from an ecological perspective.

  19. Construction of predictive models for recurrence and progression in >1000 patients with non-muscle-invasive bladder cancer (NMIBC) from a single centre.

    Science.gov (United States)

    Ali-El-Dein, Bedeir; Sooriakumaran, Prasanna; Trinh, Quoc-Dien; Barakat, Tamer S; Nabeeh, Adel; Ibrahiem, El-Housseiny I

    2013-06-01

    To construct predictive models based on the objectively calculated risks of progression and recurrence of non-muscle-invasive bladder cancer (NMIBC) in a large cohort of patients from a single centre. Between October 1984 and March 2009 a cohort of 1019 patients (877 males; 142 females; median age 44 years) with histologically confirmed NMIBC was included in this study. Among these patients, 74% received bacillus Calmette-Guérin (BCG)-based therapy. Complete transurethral resection of bladder tumour of all visible tumours was carried out in all patients, and the stage and grade were determined. Univariate analysis and multivariate Cox regression were used to identify predictors of recurrence and progression. The studied predictors included age, sex, stage, grade, associated carcinoma in situ, tumour size, multiplicity, macroscopic appearance of the tumour, history of recurrence and type of adjuvant intravesical therapy. Multivariate logistic regression models were used to develop the 12- and 60-month recurrence and progression predictive models. The predictive accuracy of the models was assessed for discrimination as well as calibration. The median (range) follow-up was 44 (6-254) months. On multivariate analysis, stage, multiplicity, history of recurrence and adjuvant intravesical therapy were significantly associated with recurrence, whereas for progression only tumour grade and size were significant independent predictors. The constructed nomograms had a 64.9% and 69.4% chance of correctly distinguishing between two patients, one destined to have a recurrence and one not at 12 and 60 months, respectively. The constructed nomograms had a 70.2% and 73.5% chance of correctly distinguishing between two patients, one destined to progress and one not at 12 and 60 months, respectively. All predictive models were well calibrated. Based on multivariate analysis of the studied prognostic factors nomograms for predicting recurrence and progression in NMIBC were

  20. Non-invasive diagnostic methods for atherosclerosis and use in assessing progression and regression in hypercholesterolemia

    International Nuclear Information System (INIS)

    Tsushima, Motoo; Fujii, Shigeki; Yutani, Chikao; Yamamoto, Akira; Naitoh, Hiroaki.

    1990-01-01

    We evaluated the wall thickening and stenosis rate (ASI), the calcification rate (ACI), and the wall thickening and calcification stenosis rate (SCI) of the lower abdominal aorta calculated by the 12 sector method from simple or enhanced computed tomography. The intra-observer variation of the calculation of ASI was 5.7% and that of ACI was 2.4%. In 9 patients who underwent an autopsy examination, ACI was significantly correlated with the rate of the calcification dimension to the whole objective area of the abdominal aorta (r=0.856, p<0.01). However, there were no correlations between ASI and the surface involvement or the atherosclerotic index obtained by the point-counting method of the autopsy materials. In the analysis of 40 patients with atherosclerotic vascular diseases, ASI and ACI were also highly correlated with the percentage volume of the arterial wall in relation to the whole volume of the observed artery (r=0.852, p<0.0001) and also the percentage calcification volume (r=0.913, p<0.0001) calculated by the computed method, respectively. The percentage of atherosclerotic vascular diseases increased in the group of both high ASI (over 10%) and high ACI (over 20%). We used SCI as a reliable index when the progression and regression of atherosclerosis was considered. Among patients of hypercholesterolemia consisting of 15 with familial hypercholesterolemia (FH) and 6 non-FH patients, the change of SCI (d-SCI) was significantly correlated with the change of total cholesterol concentration (d-TC) after the treatment (r=0.466, p<0.05) and the change of the right Achilles' tendon thickening (d-ATT) was also correlated with d-TC (r=0.634, p<0.005). However, no correlation between d-SCI and d-ATT was observed. In conclusion, CT indices of atherosclerosis were useful as a noninvasive quantitative diagnostic method and we were able to use them to assess the progression and regression of atherosclerosis. (author)

  1. 3-D spectral IP imaging: Non-invasive characterization of contaminant plumes. 1998 annual progress report

    International Nuclear Information System (INIS)

    Lesmes, D.; Morgan, F.D.; Rodi, W.

    1998-01-01

    'The overall objective of this project is to develop the scientific basis for characterizing contaminant plumes in the earth''s subsurface using field measurements of induced polarization (IP) effects. Three specific objectives towards this end are: (1) understanding IP at the laboratory level through measurements of complex resistivity as a function of frequency in rock and soil samples with varying pore geometries, pore fluid conductivities and saturations, and contaminant chemistries and concentrations; (2) developing effective data acquisition techniques for measuring the critical IP responses (time domain or frequency domain) in the field; (3) developing modeling and inversion algorithms that permit the interpretation of field IP data in terms of subsurface geology and contaminant plume properties. The authors laboratory experiments to date are described in Appendices A and B, which consist of two papers submitted to the annual SAGEEP conference (Frye et al., 1998; Sturrock et al., 1998). The experiments involved measurements of complex resistivity vs. frequency on a suite of brine saturated sandstone samples. In one set of experiments, the fluid chemistry (pH, ionic strength, and cation type) was varied. In a second set of experiments, the microgeometry of the rock matrix was varied. The experiments showed that spectral IP responses are sensitive to subtle variations in both the solution chemistry and rock microgeometry. The results demonstrate that spectral IP responses have the potential of being sensitive indicators of in-situ chemistry and microgeometry, the latter of which may be related to the hydraulic properties. Data Acquisition The authors have been looking in some detail at the effects of electromagnetic coupling and how to practically deal with it. In this area, the results to date are summarized in Vandiver (1998). The progress in the development of modeling and inversion algorithms for IP is described in Appendix C, a paper submitted to the

  2. [Non-invasive evaluation of the cardiac autonomic nervous system by PET]. Progress report

    Energy Technology Data Exchange (ETDEWEB)

    1992-12-01

    C-11 hydroxy ephedrine, introduced as the first clinically usable norepinephrine analogue, studies employing normal volunteers and patients with various cardiac disorders was found to valuable as a nonadreneric tracer. Simultaneously, animal studies been used to assess its use following ischemic injury in order to define neuronal damage. Current research focuses on the comparison of C-11 hydroxyephedrine with other neurotransmitters such as C-11 epinephrine and C-11 threohydroxyephedrine. Epinephrine is primarily stored in vesicles of the nerve terminal, while threo-hydroxyephedrine is only substrate to uptake I mechanism. Such a combination of radiotracers may allow the dissection of uptake I mechanism as well as vesicular storage. In parallel to the refinement of presynaptic tracers for the sympathetic nervous system, we are developing radiopharmaceuticals to delineate the adrenergic receptors in the heart. The combined evaluation of pre- and postsynaptic nerve function will improve our ability to identify abnormalides. We are currently developing a new radiosynthesis of the hydrophilic adrenergic receptor antagonist C-11 CGP-12177 which has been used by others for the visualization of adrenergic receptors in the heart. We are developing radiopharmaceuticals, for the delineation of presynaptic cholinergic nerve terminals. Derivatives of benzovesamicol have been labeled in our institution and are currently under investigation. The most promising agent is F-18 benzovesamicol (FEBOBV) which allows the visualization of parasympathetic nerve terminals in the canine heart as demonstrated by, preliminary PET data.

  3. Peripheral Lesions Identified on Ultrawide Field Imaging Predict Increased Risk of Diabetic Retinopathy Progression over 4 Years.

    Science.gov (United States)

    Silva, Paolo S; Cavallerano, Jerry D; Haddad, Nour Maya N; Kwak, Hanna; Dyer, Kelli H; Omar, Ahmed F; Shikari, Hasanain; Aiello, Lloyd M; Sun, Jennifer K; Aiello, Lloyd Paul

    2015-05-01

    To determine whether peripheral diabetic retinopathy (DR) lesions identified on ultrawide field (UWF) imaging are associated with increased DR progression. Prospective, longitudinal cohort. Two hundred eyes of 100 participants previously enrolled in a comparative instrument validation study. Baseline mydriatic 7-standard field Early Treatment Diabetic Retinopathy Study (ETDRS) photographs and UWF images were obtained. On UWF images, DR lesions with a greater extent outside versus inside standard ETDRS fields were defined as predominantly peripheral lesions (PPLs). Follow-up ETDRS photographs were obtained 4.2±0.3 years after baseline. Baseline and follow-up DR severity were graded from ETDRS photographs. Rates of 2-step or more progression and progression to proliferative DR (PDR) in eyes with PPLs compared with eyes without PPLs identified on UWF imaging at baseline. In eyes without PDR (n = 109) at baseline, 56 (51%) had at least 1 field with PPLs and 43 (39%) had DR progression. Compared with eyes without PPLs, eyes with PPLs had a 3.2-fold increased risk of 2-step or more DR progression (6 [11%] vs. 19 [34%]; P = 0.005) and a 4.7-fold increased risk for progression to PDR (3 [6%] vs. 14 [25%]; P = 0.005). These findings remained statistically significant after adjusting for gender, diabetes type, diabetes duration, hemoglobin A1c (HbA1c) levels, and baseline DR severity. Increasing extent of fields with PPLs increased the risk for 2-step or more DR progression (P = 0.004) and progression to PDR (P = 0.009). Presence and increasing extent of PPLs were associated with increased risk of DR progression over 4 years, independent of baseline DR severity and HbA1c levels. Increasing extent of PPLs substantially increased the risk of DR progression and progression to PDR, especially with less severe DR at baseline. These findings demonstrate that detailed peripheral retinal evaluation provides important information that is necessary to assess completely the risk of DR

  4. Huntington's disease biomarker progression profile identified by transcriptome sequencing in peripheral blood

    NARCIS (Netherlands)

    Mastrokolias, A.; Ariyurek, Y.; Goeman, J.J.; Duijn, E. van; Roos, R.A.; Mast, R.C. van der; Ommen, G.B. van; Dunnen, J.T. den; Hoen, P.A.C. 't; Roon-Mom, W.M. van

    2015-01-01

    With several therapeutic approaches in development for Huntington's disease, there is a need for easily accessible biomarkers to monitor disease progression and therapy response. We performed next-generation sequencing-based transcriptome analysis of total RNA from peripheral blood of 91 mutation

  5. Role of Molecular Genetics in Identifying ‘Fine Tuned’ Natural Enemies of the Invasive Brazilian Peppertree, Schinus terebinthifolius

    Science.gov (United States)

    Brazilian peppertree is a highly successful invasive species in the continental United States, Hawaiian archipelago, several Caribbean Islands, Australia, Bermuda, and a number of other countries worldwide. It also is one of only a few invasive intraspecific hybrids that has been well characterized ...

  6. Quantitative in vivo analyses reveal calcium-dependent phosphorylation sites and identifies a novel component of the Toxoplasma invasion motor complex.

    Directory of Open Access Journals (Sweden)

    Thomas Nebl

    2011-09-01

    Full Text Available Apicomplexan parasites depend on the invasion of host cells for survival and proliferation. Calcium-dependent signaling pathways appear to be essential for micronemal release and gliding motility, yet the target of activated kinases remains largely unknown. We have characterized calcium-dependent phosphorylation events during Toxoplasma host cell invasion. Stimulation of live tachyzoites with Ca²⁺-mobilizing drugs leads to phosphorylation of numerous parasite proteins, as shown by differential 2-DE display of ³²[P]-labeled protein extracts. Multi-dimensional Protein Identification Technology (MudPIT identified ∼546 phosphorylation sites on over 300 Toxoplasma proteins, including 10 sites on the actomyosin invasion motor. Using a Stable Isotope of Amino Acids in Culture (SILAC-based quantitative LC-MS/MS analyses we monitored changes in the abundance and phosphorylation of the invasion motor complex and defined Ca²⁺-dependent phosphorylation patterns on three of its components--GAP45, MLC1 and MyoA. Furthermore, calcium-dependent phosphorylation of six residues across GAP45, MLC1 and MyoA is correlated with invasion motor activity. By analyzing proteins that appear to associate more strongly with the invasion motor upon calcium stimulation we have also identified a novel 15-kDa Calmodulin-like protein that likely represents the MyoA Essential Light Chain of the Toxoplasma invasion motor. This suggests that invasion motor activity could be regulated not only by phosphorylation but also by the direct binding of calcium ions to this new component.

  7. A Canine Audience: The Effect of Animal-Assisted Therapy on Reading Progress among Students Identified with Learning Disabilities

    Science.gov (United States)

    Griess, Julie Omodio

    2010-01-01

    This study explored the use of animal-assisted therapy with students identified with a learning disability and limited reading success. Initially, reading progress was defined as the participants' comprehension rate obtained from an oral Informal Reading Inventory (IRI) passage. The nature of the Informal Reading Inventory requires the…

  8. Using Fuzzy Logic to Identify Schools Which May Be Misclassified by the No Child Left Behind Adequate Yearly Progress Policy

    Science.gov (United States)

    Yates, Donald W.

    2009-01-01

    This investigation developed, tested, and prototyped a Fuzzy Inference System (FIS) that would assist decision makers in identifying schools that may have been misclassified by existing Adequate Yearly Progress (AYP) methods. This prototype was then used to evaluate Louisiana elementary schools using published school data for Academic Year 2004. …

  9. DNA ploidy analysis by image cytometry helps to identify oral epithelial dysplasias with a high risk of malignant progression.

    Science.gov (United States)

    Torres-Rendon, A; Stewart, R; Craig, G T; Wells, M; Speight, P M

    2009-06-01

    Abnormal DNA content (aneuploidy) has been associated with malignant and premalignant epithelial lesions. The presence of aneuploidy in tumours at an early stage and in dysplastic lesions suggests that analysis of DNA content may be a useful marker for determination of prognosis in these lesions. The aim of this study was to use DNA image cytometry to evaluate aneuploidy in oral dysplastic lesions and to determine whether aneuploidy is associated with malignant progression. Forty-two lesions of oral epithelial dysplasias (OED) that had progressed to oral squamous cell carcinoma (OSCC) and 44 lesions that did not progress were analysed for DNA ploidy using image cytometry of nuclear monolayers prepared from paraffin-embedded tissue. Forty-two OSCC that had arisen from the OED cases and five samples of normal oral mucosa samples (NOM) were also examined. Aneuploidy was found in 14/42 (33.3%) of the OED that progressed, but in only 5/44 (11.3%) of OED that did not progress (p=0.01). A total of 19 OED were aneuploid of which 74% showed malignant progression compared to only 42% of the diploid lesions. The sensitivity and specificity of DNA image cytometry to detect cases with high risk of malignant progression was 0.33 and 0.88, respectively. The PPV and NPV were 0.74 and 0.58. We conclude that aneuploid oral dysplastic lesions have a high risk of malignant progression and that DNA image cytometry might help to identify those lesions most at risk.

  10. Identifying Indicators of Progress in Thermal Spray Research Using Bibliometrics Analysis

    Science.gov (United States)

    Li, R.-T.; Khor, K. A.; Yu, L.-G.

    2016-12-01

    We investigated the research publications on thermal spray in the period of 1985-2015 using the data from Web of Science, Scopus and SciVal®. Bibliometrics analysis was employed to elucidate the country and institution distribution in various thermal spray research areas and to characterize the trends of topic change and technology progress. Results show that China, USA, Japan, Germany, India and France were the top countries in thermal spray research, and Xi'an Jiaotong University, Universite de Technologie Belfort-Montbeliard, Shanghai Institute of Ceramics, ETH Zurich, National Research Council of Canada, University of Limoges were among the top institutions that had high scholarly research output during 2005-2015. The terms of the titles, keywords and abstracts of the publications were analyzed by the Latent Dirichlet Allocation model and visually mapped using the VOSviewer software to reveal the progress of thermal spray technology. It is found that thermal barrier coating was consistently the main research area in thermal spray, and high-velocity oxy-fuel spray and cold spray developed rapidly in the last 10 years.

  11. Whole-genome and Transcriptome Sequencing of Prostate Cancer Identify New Genetic Alterations Driving Disease Progression

    DEFF Research Database (Denmark)

    Ren, Shancheng; Wei, Gong-Hong; Liu, Dongbing

    2018-01-01

    BACKGROUND: Global disparities in prostate cancer (PCa) incidence highlight the urgent need to identify genomic abnormalities in prostate tumors in different ethnic populations including Asian men. OBJECTIVE: To systematically explore the genomic complexity and define disease-driven genetic alter...

  12. [Progress of methodology for identifying target protein of natural active small molecules].

    Science.gov (United States)

    Tu, Peng-Fei; Zeng, Ke-Wu; Liao, Li-Xi; Song, Xiao-Min

    2016-01-01

    Drug targets are special molecules that can interact with drugs and exert pharmacological functions in human body. The natural active small molecules are the bioactive basis of traditional Chinese medicine, and the mechanism study is a hot topic now, especially for the identification of their target proteins. However, little progress has been made in this field until now. Here, we summarized the recent technologies and methods for the identification of target proteins of natural bioactive small molecules, and introduced the main research methods, principles and successful cases in this field. We also explored the applicability and discussed the advantages and disadvantages among different methods. We hope this review can be used as a reference for the researchers who engaged in natural pharmaceutical chemistry, pharmacology and chemical biology. Copyright© by the Chinese Pharmaceutical Association.

  13. Expression profiling of cervical cancers in Indian women at different stages to identify gene signatures during progression of the disease

    International Nuclear Information System (INIS)

    Thomas, Asha; Mahantshetty, Umesh; Kannan, Sadhana; Deodhar, Kedar; Shrivastava, Shyam K; Kumar-Sinha, Chandan; Mulherkar, Rita

    2013-01-01

    Cervical cancer is the second most common cancer among women worldwide, with developing countries accounting for >80% of the disease burden. Although in the West, active screening has been instrumental in reducing the incidence of cervical cancer, disease management is hampered due to lack of biomarkers for disease progression and defined therapeutic targets. Here we carried out gene expression profiling of 29 cervical cancer tissues from Indian women, spanning International Federation of Gynaecology and Obstetrics (FIGO) stages of the disease from early lesion (IA and IIA) to progressive stages (IIB and IIIA–B), and identified distinct gene expression signatures. Overall, metabolic pathways, pathways in cancer and signaling pathways were found to be significantly upregulated, while focal adhesion, cytokine–cytokine receptor interaction and WNT signaling were downregulated. Additionally, we identified candidate biomarkers of disease progression such as SPP1, proliferating cell nuclear antigen (PCNA), STK17A, and DUSP1 among others that were validated by quantitative real-time polymerase chain reaction (qRT-PCR) in the samples used for microarray studies as well in an independent set of 34 additional samples. Integrative analysis of our results with other cervical cancer profiling studies could facilitate the development of multiplex diagnostic markers of cervical cancer progression

  14. Predatory functional response and prey choice identify predation differences between native/invasive and parasitised/unparasitised crayfish.

    Directory of Open Access Journals (Sweden)

    Neal R Haddaway

    Full Text Available BACKGROUND: Invasive predators may change the structure of invaded communities through predation and competition with native species. In Europe, the invasive signal crayfish Pacifastacus leniusculus is excluding the native white clawed crayfish Austropotamobius pallipes. METHODOLOGY AND PRINCIPAL FINDINGS: This study compared the predatory functional responses and prey choice of native and invasive crayfish and measured impacts of parasitism on the predatory strength of the native species. Invasive crayfish showed a higher (>10% prey (Gammarus pulex intake rate than (size matched natives, reflecting a shorter (16% prey handling time. The native crayfish also showed greater selection for crustacean prey over molluscs and bloodworm, whereas the invasive species was a more generalist predator. A. pallipes parasitised by the microsporidian parasite Thelohania contejeani showed a 30% reduction in prey intake. We suggest that this results from parasite-induced muscle damage, and this is supported by a reduced (38% attack rate and increased (30% prey handling time. CONCLUSIONS AND SIGNIFICANCE: Our results indicate that the per capita (i.e., functional response difference between the species may contribute to success of the invader and extinction of the native species, as well as decreased biodiversity and biomass in invaded rivers. In addition, the reduced predatory strength of parasitized natives may impair their competitive abilities, facilitating exclusion by the invader.

  15. The HLJ1-targeting drug screening identified Chinese herb andrographolide that can suppress tumour growth and invasion in non-small-cell lung cancer.

    Science.gov (United States)

    Lai, Yi-Hua; Yu, Sung-Liang; Chen, Hsuan-Yu; Wang, Chi-Chung; Chen, Huei-Wen; Chen, Jeremy J W

    2013-05-01

    HLJ1 is a novel tumour suppressor and is a potential druggable target for non-small-cell lung cancer (NSCLC). In this report, using a promoter-containing enhancer region as the HLJ1-targeting drug-screening platform, we identified several herbal compounds from a Chinese herbal bank with the capacity to enhance HLJ1 promoter activity and suppress tumour growth and invasion of NSCLC. Among the herbal drugs identified, the andrographolide (from Andrographis paniculata [Burm. f.] Nees.) most significantly induced HLJ1 expression and suppressed tumorigenesis both in vitro and in vivo. The andrographolide upregulates HLJ1 via JunB activation, which modulates AP-2α binding at the MMP-2 promoter and represses the expression of MMP-2. In addition, silencing of HLJ1 partially reverses the inhibition of cancer-cell invasion by andrographolide. Microarray transcriptomic analysis was performed to comprehensively depict the andrographolide-regulated signalling pathways. We showed that andrographolide can affect 939 genes (analysis of variance, false discovery rate andrographolide on anticancer invasion and proliferation. In conclusion, the HLJ1-targeting drug-screening platform is useful for screening of novel anticancer compounds. Using this platform, we identified andrographolide is a promising new anticancer agent that could suppress tumour growth and invasion in NSCLC.

  16. A computational study identifies HIV progression-related genes using mRMR and shortest path tracing.

    Directory of Open Access Journals (Sweden)

    Chengcheng Ma

    Full Text Available Since statistical relationships between HIV load and CD4+ T cell loss have been demonstrated to be weak, searching for host factors contributing to the pathogenesis of HIV infection becomes a key point for both understanding the disease pathology and developing treatments. We applied Maximum Relevance Minimum Redundancy (mRMR algorithm to a set of microarray data generated from the CD4+ T cells of viremic non-progressors (VNPs and rapid progressors (RPs to identify host factors associated with the different responses to HIV infection. Using mRMR algorithm, 147 gene had been identified. Furthermore, we constructed a weighted molecular interaction network with the existing protein-protein interaction data from STRING database and identified 1331 genes on the shortest-paths among the genes identified with mRMR. Functional analysis shows that the functions relating to apoptosis play important roles during the pathogenesis of HIV infection. These results bring new insights of understanding HIV progression.

  17. Progress in Australian dendroclimatology: Identifying growth limiting factors in four climate zones.

    Science.gov (United States)

    Haines, Heather A; Olley, Jon M; Kemp, Justine; English, Nathan B

    2016-12-01

    Dendroclimatology can be used to better understand past climate in regions such as Australia where instrumental and historical climate records are sparse and rarely extend beyond 100years. Here we review 36 Australian dendroclimatic studies which cover the four major climate zones of Australia; temperate, arid, subtropical and tropical. We show that all of these zones contain tree and shrub species which have the potential to provide high quality records of past climate. Despite this potential only four dendroclimatic reconstructions have been published for Australia, one from each of the climate zones: A 3592year temperature record for the SE-temperate zone, a 350year rainfall record for the Western arid zone, a 140year rainfall record for the northern tropics and a 146year rainfall record for SE-subtropics. We report on the spatial distribution of tree-ring studies, the environmental variables identified as limiting tree growth in each study, and identify the key challenges in using tree-ring records for climate reconstruction in Australia. We show that many Australian species have yet to be tested for dendroclimatological potential, and that the application of newer techniques including isotopic analysis, carbon dating, wood density measurements, and anatomical analysis, combined with traditional ring-width measurements should enable more species in each of the climate zones to be used, and long-term climate records to be developed across the entire continent. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Application of Circulating Tumor DNA as a Non-Invasive Tool for Monitoring the Progression of Colorectal Cancer.

    Directory of Open Access Journals (Sweden)

    Jiaolin Zhou

    Full Text Available Liquid biopsy has been proposed to be a promising noninvasive tool to obtain information on tumor progression. Through a clinical observation of a case series of 6 consecutive patients, we aim to determine the value of circulating tumor DNA (ctDNA for monitoring the tumor burden during the treatment of colorectal cancer (CRC.We used capture sequencing of 545 genes to identify somatic alternations in primary tumor tissues of the six CRC patients who underwent radical surgery and in 23 plasma samples collected at serial time points. We compared the mutation patterns and variant allele frequencies (VAFs between the matched tissue and the plasma samples and evaluated the potential advantage of using ctDNA as a better tumor load indicator to detect disease relapse over carcinoembryonic antigen (CEA, cancer antigen (CA 19-9 and imaging studies.We identified low-frequency mutations with a mean VAF of 0.88% (corresponding to a mean tumor burden of 0.20ng/mL in the preoperative plasmas of four patients with locally advanced CRC and a subset of mutations shared by their primary tumors. The tumor loads appeared a sudden decrease upon surgery or other adjuvant treatments and then generally maintained at low levels (0.092ng/mL until disease recurred. ctDNA increased by 13-fold when disease relapsed in one patient while the CEA and CA 19-9 levels remained normal. In this patient, all six somatic mutations identified in the preoperative plasma were detected in the recrudescent plasma again, with five mutations showing allele fraction increase.We described a multi-time-point profile of ctDNA of CRC patients during the course of comprehensive treatment and observed a correlation of ctDNA level with the clinically evaluated tumor progression. This demonstrated a new strategy by analyzing the heterogeneous ctDNA to evaluate and monitor the tumor burden in the treatment and follow-up of CRC patients, with potentially better potency than conventional biomarkers.

  19. DNA fingerprinting tags novel altered chromosomal regions and identifies the involvement of SOX5 in the progression of prostate cancer.

    Science.gov (United States)

    Ma, Stephanie; Chan, Yuen Piu; Woolcock, Bruce; Hu, Liang; Wong, Kai Yau; Ling, Ming Tat; Bainbridge, Terry; Webber, Douglas; Chan, Tim Hon Man; Guan, Xin-Yuan; Lam, Wan; Vielkind, Juergen; Chan, Kwok Wah

    2009-05-15

    Identification of genomic alterations associated with the progression of prostate cancer may facilitate the better understanding of the development of this highly variable disease. Matched normal, premalignant high-grade prostatic intraepithelial neoplasia and invasive prostate carcinoma cells were procured by laser capture microdissection (LCM) from human radical prostatectomy specimens. From these cells, comparative DNA fingerprints were generated by a modified PCR-based technique called scanning of microdissected archival lesion (SMAL)-PCR. Recurrent polymorphic fingerprint fragments were used in tagging altered chromosomal regions. Altered regions were found at cytobands 1p31.3, 1q44, 2p23.1, 3p26.3, 3q22.3, 4q22.3, 4q35.2, 5q23.2, 8q22.3, 8q24.13, 9q21.3, 9q22.32, 10q11.21, 11p13, 12p12.1, 13q12.1, 16q12.2 and 18q21.31. Candidate genes in the surrounding area that may possibly harbor mutations that change normal prostatic cells to progress into their tumor stages were proposed. Of these fragments, a 420 bp alteration, absent in all 26 normal samples screened, was observed in 2 tumors. This fragment was cloned, sequenced and localized to chromosome 12p12.1. Within this region, candidate gene sex determining region Y-box 5 (SOX5) was proposed. Further studies of SOX5 in cell lines, xenografts and human prostate specimens, at both the RNA and protein levels, found overexpression of the gene in tumors. This overexpression was then subsequently found by fluorescent in situ hybridization to be caused by amplification of the region. In conclusion, our results suggest LCM coupled with SMAL-PCR DNA fingerprinting is a useful method for the screening and identification of chromosomal regions and genes associated with cancer development. Further, overexpression of SOX5 is associated with prostate tumor progression and early development of distant metastasis. (c) 2008 Wiley-Liss, Inc.

  20. LDH-A promotes malignant progression via activation of epithelial-to-mesenchymal transition and conferring stemness in muscle-invasive bladder cancer

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Fujin [Department of Urinary Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu (China); Department of Urinary Surgery, Huai' an Hospital to Xuzhou Medical University, Huai' an, Jiangsu (China); Ma, Song [Department of Urinary Surgery, Huai' an Hospital to Xuzhou Medical University, Huai' an, Jiangsu (China); Xue, Yubao [Department of Medical Oncology, Huai' an Hospital to Xuzhou Medical University, Huai' an, Jiangsu (China); Hou, Jianquan, E-mail: Jianquanhou@aliyun.com [Department of Urinary Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu (China); Zhang, Yongjie, E-mail: zhangyj0818@126.com [Department of Medical Oncology, Huai' an Hospital to Xuzhou Medical University, Huai' an, Jiangsu (China)

    2016-01-22

    Lactate dehydrogenase-A(LDH-A) is an important rate-limiting enzyme in the Warburg effect. Survival analysis indicated poor clinical outcomes in MIBC with high LDH-A expression. The results of in vitro experiment indicated that LDH-A promotes MIBC cells proliferation, invasion and migration. The positive relationship between LDH-A expression and CSC/EMT markers was confirmed both in invasive bladder cell line and in 136 MIBC specimens. Thus, we conclude that LDH-A may be a promising target for MIBC. - Highlights: • Survival analysis indicated poor clinical outcomes in MIBC with high LDH-A expression. • IHC analysis of 136 MIBC specimens revealed increased LDH-A is correlated with positive Oct4 and negative E-cadherin. • In vitro experiments demonstrated LDH-A promotes MIBC progression by positive regulation of EMT/CSC.

  1. Comparative Gene Expression Analyses Identify Luminal and Basal Subtypes of Canine Invasive Urothelial Carcinoma That Mimic Patterns in Human Invasive Bladder Cancer.

    Directory of Open Access Journals (Sweden)

    Deepika Dhawan

    Full Text Available More than 160,000 people are expected to die from invasive urothelial carcinoma (iUC this year worldwide. Research in relevant animal models is essential to improving iUC management. Naturally-occurring canine iUC closely resembles human iUC in histopathology, metastatic behavior, and treatment response, and could provide a relevant model for human iUC. The molecular characterization of canine iUC, however, has been limited. Work was conducted to compare gene expression array results between tissue samples from iUC and normal bladder in dogs, with comparison to similar expression array data from human iUC and normal bladder in the literature. Considerable similarities between enrichment patterns of genes in canine and human iUC were observed. These included patterns mirroring basal and luminal subtypes initially observed in human breast cancer and more recently noted in human iUC. Canine iUC samples also exhibited enrichment for genes involved in P53 pathways, as has been reported in human iUC. This is particularly relevant as drugs targeting these genes/pathways in other cancers could be repurposed to treat iUC, with dogs providing a model to optimize therapy. As part of the validation of the results and proof of principal for evaluating individualized targeted therapy, the overexpression of EGFR in canine bladder iUC was confirmed. The similarities in gene expression patterns between dogs and humans add considerably to the value of naturally-occurring canine iUC as a relevant and much needed animal model for human iUC. Furthermore, the finding of expression patterns that cross different pathologically-defined cancers could allow studies of dogs with iUC to help optimize cancer management across multiple cancer types. The work is also expected to lead to a better understanding of the biological importance of the gene expression patterns, and the potential application of the cross-species comparisons approach to other cancer types as well.

  2. Characterization of increasing stages of invasiveness identifies stromal/cancer cell crosstalk in rat models of mesothelioma.

    Science.gov (United States)

    Nader, Joëlle S; Abadie, Jérôme; Deshayes, Sophie; Boissard, Alice; Blandin, Stéphanie; Blanquart, Christophe; Boisgerault, Nicolas; Coqueret, Olivier; Guette, Catherine; Grégoire, Marc; Pouliquen, Daniel L

    2018-03-27

    Sarcomatoid mesothelioma (SM) is a devastating cancer associated with one of the poorest outcome. Therefore, representative preclinical models reproducing different tumor microenvironments (TME) observed in patients would open up new prospects for the identification of markers and evaluation of innovative therapies. Histological analyses of four original models of rat SM revealed their increasing infiltrative and metastatic potential were associated with differences in Ki67 index, blood-vessel density, and T-lymphocyte and macrophage infiltration. In comparison with the noninvasive tumor M5-T2, proteomic analysis demonstrated the three invasive tumors F4-T2, F5-T1 and M5-T1 shared in common a very significant increase in the abundance of the multifunctional proteins galectin-3, prohibitin and annexin A5, and a decrease in proteins involved in cell adhesion, tumor suppression, or epithelial differentiation. The increased metastatic potential of the F5-T1 tumor, relative to F4-T2, was associated with an increased macrophage vs T-cell infiltrate, changes in the levels of expression of a panel of cytokine genes, an increased content of proteins involved in chromatin organization, ribosome structure, splicing, or presenting anti-adhesive properties, and a decreased content of proteins involved in protection against oxidative stress, normoxia and intracellular trafficking. The most invasive tumor, M5-T1, was characterized by a pattern of specific phenotypic and molecular features affecting the presentation of MHC class I-mediated antigens and immune cell infiltration, or involved in the reorganization of the cytoskeleton and composition of the extracellular matrix. These four preclinical models and data represent a new resource available to the cancer research community to catalyze further investigations on invasiveness.

  3. Molecular markers increase precision of the European Association of Urology non-muscle invasive bladder cancer progression risk groups

    DEFF Research Database (Denmark)

    Van Kessel, Kim E.; van der Keur, Kirstin A.; Dyrskjøt, Lars

    2018-01-01

    PURPOSE: The European Association of Urology (EAU) guidelines for non-muscle invasive bladder cancer (NMIBC) recommend risk stratification based on clinicopathological parameters. Our aim was to investigate the added value of biomarkers to improve risk stratification of NMIBC. EXPERIMENTAL DESIGN...

  4. Coexpression of invasive markers (uPA, CD44) and multiple drug-resistance proteins (MDR1, MRP2) is correlated with epithelial ovarian cancer progression

    Science.gov (United States)

    Chen, H; Hao, J; Wang, L; Li, Y

    2009-01-01

    Background: Invasion and metastases of cancer cells and the development of resistance to anticancer therapies are the main causes of treatment failure and mortality in cancer patients. Methods: We evaluated invasive markers of urokinase plasminogen activator (uPA) and CD44 and multiple drug-resistance (MDR) markers of MDR1 and MRP2 in four epithelial ovarian cancer (EOC) cell lines, primary tumours (n=120) and matched metastatic lesions (n=40) by immunofluoresence labelling. We correlated uPA and CD44 with MDR markers in primary and metastatic cells using confocal microscope. We also investigated the relationship of the expression of uPA, CD44 and MDR1 with various progression parameters. Results: The coexpression of uPA and CD44 with MDR markers was found in primary and metastatic cells. The overexpression of uPA, CD44 and MDR1 was found in most primary and matched metastatic lesions of EOC, and was significantly associated with tumour stage, grade, residual disease status, relapse and presence of ascites (P0.05). Conclusions: Our results suggest that the overexpression of uPA, CD44 and MRD1 is correlated with EOC progression; both uPA and CD44 are related with drug resistance during EOC metastasis and could be useful therapeutically. PMID:19603017

  5. Reduced immunohistochemical PTEN staining is associated with higher progression rate and recurrence episodes in non-invasive low-grade papillary urothelial carcinoma of the bladder.

    Science.gov (United States)

    Kulac, Ibrahim; Arslankoz, Sehbal; Netto, George J; Ertoy Baydar, Dilek

    2018-01-24

    Non-invasive low-grade papillary urothelial carcinoma (NILGPUC) of the bladder is regarded as a relatively indolent disease. However, its propensity for frequent recurrences constitutes a major clinical problem. Additionally, there is a progression risk of 10-15% to either a higher grade and/or a higher stage disease in these tumors. The molecular factors that will predict recurrence and progression in low-grade pTa bladder carcinoma have not yet been elucidated. Herein, we investigated the association of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) alterations with recurrence and progression in NILGPUC using immunohistochemistry. Eighty-one cases of bladder cancer initially diagnosed as NILGPUC in a single institution with follow-up were encountered after searching medical records. Tissue microarrays (TMA) that contained both tumor and non-neoplastic mucosa from each case were constructed using paraffin blocks of transurethral resections. Sections from TMA blocks were stained immunohistochemically for PTEN protein and were evaluable in 76 cases. Any absence of staining was recorded and correlated with clinical findings. Ten patients (13.2%) showed progression and 41 (53.9%) showed recurrence. Reduced PTEN expression was observed in 29 cases (38.1%). Cases with reduced PTEN had higher progression rate compared to cases with intact PTEN (p = 0.026). Tumor relapse was more frequent in cases with reduced PTEN (65.5 vs 46.8%), but this difference was not statistically significant (p = 0.112). On the other hand, decreased PTEN expression was associated with higher number of recurrence episodes (p = 0.002). PTEN seems to have a link with the disease course in NILGPUC of the bladder.

  6. A native species with invasive behaviour in coastal dunes: evidence for progressing decay and homogenization of habitat types

    DEFF Research Database (Denmark)

    Nielsen, Knud Erik; Degn, Hans Jørgen; Damgaard, Christian

    2011-01-01

    A new species has recently invaded coastal dune ecosystems in North West Europe. The native and expansive inland grass, Deschampsia flexuosa, progressively dominating inland heaths, has recently invaded coastal dunes in Denmark, occasionally even as a dominant species. A total of 222 coastal loca...

  7. Serum Metabolomics to Identify the Liver Disease-Specific Biomarkers for the Progression of Hepatitis to Hepatocellular Carcinoma

    Science.gov (United States)

    Gao, Rong; Cheng, Jianhua; Fan, Chunlei; Shi, Xiaofeng; Cao, Yuan; Sun, Bo; Ding, Huiguo; Hu, Chengjin; Dong, Fangting; Yan, Xianzhong

    2015-12-01

    Hepatocellular carcinoma (HCC) is a common malignancy that has region specific etiologies. Unfortunately, 85% of cases of HCC are diagnosed at an advanced stage. Reliable biomarkers for the early diagnosis of HCC are urgently required to reduced mortality and therapeutic expenditure. We established a non-targeted gas chromatography-time of flight-mass spectrometry (GC-TOFMS) metabolomics method in conjunction with Random Forests (RF) analysis based on 201 serum samples from healthy controls (NC), hepatitis B virus (HBV), liver cirrhosis (LC) and HCC patients to explore the metabolic characteristics in the progression of hepatocellular carcinogenesis. Ultimately, 15 metabolites were identified intimately associated with the process. Phenylalanine, malic acid and 5-methoxytryptamine for HBV vs. NC, palmitic acid for LC vs. HBV, and asparagine and β-glutamate for HCC vs. LC were screened as the liver disease-specific potential biomarkers with an excellent discriminant performance. All the metabolic perturbations in these liver diseases are associated with pathways for energy metabolism, macromolecular synthesis, and maintaining the redox balance to protect tumor cells from oxidative stress.

  8. Integrated molecular analysis of Tamoxifen-resistant invasive lobular breast cancer cells identifies MAPK and GRM/mGluR signaling as therapeutic vulnerabilities.

    Science.gov (United States)

    Stires, Hillary; Heckler, Mary M; Fu, Xiaoyong; Li, Zhao; Grasso, Catherine S; Quist, Michael J; Lewis, Joseph A; Klimach, Uwe; Zwart, Alan; Mahajan, Akanksha; Győrffy, Balázs; Cavalli, Luciane R; Riggins, Rebecca B

    2017-09-19

    Invasive lobular breast cancer (ILC) is an understudied malignancy with distinct clinical, pathological, and molecular features that distinguish it from the more common invasive ductal carcinoma (IDC). Mounting evidence suggests that estrogen receptor-alpha positive (ER+) ILC has a poor response to Tamoxifen (TAM), but the mechanistic drivers of this are undefined. In the current work, we comprehensively characterize the SUM44/LCCTam ILC cell model system through integrated analysis of gene expression, copy number, and mutation, with the goal of identifying actionable alterations relevant to clinical ILC that can be co-targeted along with ER to improve treatment outcomes. We show that TAM has several distinct effects on the transcriptome of LCCTam cells, that this resistant cell model has acquired copy number alterations and mutations that impinge on MAPK and metabotropic glutamate receptor (GRM/mGluR) signaling networks, and that pharmacological inhibition of either improves or restores the growth-inhibitory actions of endocrine therapy. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  9. Morphine does not facilitate breast cancer progression in two preclinical mouse models for human invasive lobular and HER2⁺ breast cancer.

    Science.gov (United States)

    Doornebal, Chris W; Vrijland, Kim; Hau, Cheei-Sing; Coffelt, Seth B; Ciampricotti, Metamia; Jonkers, Jos; de Visser, Karin E; Hollmann, Markus W

    2015-08-01

    Morphine and other opioid analgesics are potent pain-relieving agents routinely used for pain management in patients with cancer. However, these drugs have recently been associated with a worse relapse-free survival in patients with surgical cancer, thus suggesting that morphine adversely affects cancer progression and relapse. In this study, we evaluated the impact of morphine on breast cancer progression, metastatic dissemination, and outgrowth of minimal residual disease. Using preclinical mouse models for metastatic invasive lobular and HER2 breast cancer, we show that analgesic doses of morphine do not affect mammary tumor growth, angiogenesis, and the composition of tumor-infiltrating immune cells. Our studies further demonstrate that morphine, administered in the presence or absence of surgery-induced tissue damage, neither facilitates de novo metastatic dissemination nor promotes outgrowth of minimal residual disease after surgery. Together, these findings indicate that opioid analgesics can be used safely for perioperative pain management in patients with cancer and emphasize that current standards of "good clinical practice" should be maintained.

  10. Polymeric nanotheranostics for real-time non-invasive optical imaging of breast cancer progression and drug release.

    Science.gov (United States)

    Ferber, Shiran; Baabur-Cohen, Hemda; Blau, Rachel; Epshtein, Yana; Kisin-Finfer, Einat; Redy, Orit; Shabat, Doron; Satchi-Fainaro, Ronit

    2014-09-28

    Polymeric nanocarriers conjugated with low molecular weight drugs are designed in order to improve their efficacy and toxicity profile. This approach is particularly beneficial for anticancer drugs, where the polymer-drug conjugates selectively accumulate at the tumor site, due to the enhanced permeability and retention (EPR) effect. The conjugated drug is typically inactive, and upon its pH- or enzymatically-triggered release from the carrier, it regains its therapeutic activity. These settings lack information regarding drug-release time, kinetics and location. Thereby, real-time non-invasive intravital monitoring of drug release is required for theranostics (therapy and diagnostics). We present here the design, synthesis and characterization of a theranostic nanomedicine, based on N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer, owing its fluorescence-based monitoring of site-specific drug release to a self-quenched near-infrared fluorescence (NIRF) probe. We designed two HPMA copolymer-based systems that complement to a theranostic nanomedicine. The diagnostic system consists of self-quenched Cy5 (SQ-Cy5) as a reporter probe and the therapeutic system is based on the anticancer agent paclitaxel (PTX). HPMA copolymer-PTX/SQ-Cy5 systems enable site-specific release upon enzymatic degradation in cathepsin B-overexpressing breast cancer cells. The release of the drug occurs concomitantly with the activation of the fluorophore to its Turn-ON state. HPMA copolymer-SQ-Cy5 exhibits preferable body distribution and drug release compared with the free drug and probe when administered to cathepsin B-overexpressing 4T1 murine mammary adenocarcinoma-bearing mice. This approach of co-delivery of two complementary systems serves as a proof-of-concept for real-time deep tissue intravital orthotopic monitoring and may have the potential use in clinical utility as a theranostic nanomedicine. Copyright © 2014. Published by Elsevier Ireland Ltd.

  11. External validation of non-invasive prediction models for identifying ultrasonography-diagnosed fatty liver disease in a Chinese population.

    Science.gov (United States)

    Shen, Ya-Nan; Yu, Ming-Xing; Gao, Qian; Li, Yan-Yan; Huang, Jian-Jun; Sun, Chen-Ming; Qiao, Nan; Zhang, Hai-Xia; Wang, Hui; Lu, Qing; Wang, Tong

    2017-07-01

    Several prediction models for fatty liver disease (FLD) are available with limited externally validation and less comprehensive evaluation. The aim was to perform external validation and direct comparison of 4 prediction models (the Fatty Liver Index, the Hepatic Steatosis Index, the ZJU index, and the Framingham Steatosis Index) for FLD both in the overall population and the obese subpopulation.This cross-sectional study included 4247 subjects aged 20 to 65 years recruited from the north of Shanxi Province in China. Anthropometric and biochemical features were collected using standard protocols. FLD was diagnosed by liver ultrasonography. We assessed all models in terms of discrimination, calibration, and decision curve analysis.The original models performed well in terms of discrimination for the overall population, with the area under the receiver operating characteristic curves (AUCs) around 0.85, while AUCs for obese individuals were around 0.68. Nevertheless, the predicted risks did not match well with the observed risks both in the overall population and the obese subpopulation. The FLI 2006 was 1 of the 2 best models in terms of discrimination (AUCs were 0.87 and 0.72 for the overall population and the obese subgroup, respectively) and had the best performance in terms of calibration, and attained the highest net benefit.The FLI 2006 is overall the best tool to identify high risk individuals and has great clinical utility. Nonetheless, it does not perform well enough to quantify the actual risk of FLD, which need to be (re)calibrated for clinical use.

  12. Combining a Climatic Niche Model of an Invasive Fungus with Its Host Species Distributions to Identify Risks to Natural Assets: Puccinia psidii Sensu Lato in Australia

    Science.gov (United States)

    Kriticos, Darren J.; Morin, Louise; Leriche, Agathe; Anderson, Robert C.; Caley, Peter

    2013-01-01

    Puccinia psidii sensu lato (s.l.) is an invasive rust fungus threatening a wide range of plant species in the family Myrtaceae. Originating from Central and South America, it has invaded mainland USA and Hawai'i, parts of Asia and Australia. We used CLIMEX to develop a semi-mechanistic global climatic niche model based on new data on the distribution and biology of P. psidii s.l. The model was validated using independent distribution data from recently invaded areas in Australia, China and Japan. We combined this model with distribution data of its potential Myrtaceae host plant species present in Australia to identify areas and ecosystems most at risk. Myrtaceaeous species richness, threatened Myrtaceae and eucalypt plantations within the climatically suitable envelope for P. psidii s.l in Australia were mapped. Globally the model identifies climatically suitable areas for P. psidii s.l. throughout the wet tropics and sub-tropics where moist conditions with moderate temperatures prevail, and also into some cool regions with a mild Mediterranean climate. In Australia, the map of species richness of Myrtaceae within the P. psidii s.l. climatic envelope shows areas where epidemics are hypothetically more likely to be frequent and severe. These hotspots for epidemics are along the eastern coast of New South Wales, including the Sydney Basin, in the Brisbane and Cairns areas in Queensland, and in the coastal region from the south of Bunbury to Esperance in Western Australia. This new climatic niche model for P. psidii s.l. indicates a higher degree of cold tolerance; and hence a potential range that extends into higher altitudes and latitudes than has been indicated previously. The methods demonstrated here provide some insight into the impacts an invasive species might have within its climatically suited range, and can help inform biosecurity policies regarding the management of its spread and protection of valued threatened assets. PMID:23704988

  13. Obesity Enhances the Conversion of Adipose-Derived Stromal/Stem Cells into Carcinoma-Associated Fibroblast Leading to Cancer Cell Proliferation and Progression to an Invasive Phenotype

    Science.gov (United States)

    Pei, Dorothy T.; Hurst, Christian G.; Gimble, Jeffrey M.; Burow, Matthew E.

    2017-01-01

    Obesity is associated with enhanced tumor growth and progression. Within the adipose tissue are adipose-derived stromal/stem cells (ASCs) that have been shown to convert into carcinoma-associated fibroblast (CAFs) in the presence of tumor-derived factors. However, the impact of obesity on the ASCs and on the conversion of ASCs into CAFs has not been demonstrated. In the current study, ASCs isolated from lean donors (BMI  30, obASCs). The contribution of tumor-derived factors on the conversion of ASCs to CAFs was investigated. Following exposure to cancer cells, obASCs expressed higher levels of CAF markers, including NG2, alpha-SMA, VEGF, FAP, and FSP, compared to lnASCs. To investigate the crosstalk between ASCs and breast cancer cells, MCF7 cells were serially cocultured with lnASCs or obASCs. After coculture with lnASCs and obASCs, MCF7 cells demonstrated enhanced proliferation and expressed an invasive phenotype morphologically, with more pronounced effects following exposure to obASCs. Long-term exposure to obASCs also enhanced the expression of protumorgenic factors. Together, these results suggest that obesity alters ASCs to favor their rapid conversion into CAFs, which in turn enhances the proliferative rate, the phenotype, and gene expression profile of breast cancer cells. PMID:29527228

  14. Regulation of in situ to invasive breast carcinoma transition

    Energy Technology Data Exchange (ETDEWEB)

    Polyak, Kornelia; Hu, Min; Yao, Jun; Carroll, Danielle K.; Weremowicz, Stanislawa; Chen, Haiyan; Carrasco, Daniel; Richardson, Andrea; Violette, Shelia; Gelman, Rebecca S.; Bissell, Mina J.; Schnitt, Stuart; Polyak, Kornelia

    2008-05-07

    The transition of ductal carcinoma in situ (DCIS) to invasive carcinoma is a key event in breast tumor progression that is poorly understood. Comparative molecular analysis of tumor epithelial cells from in situ and invasive tumors has failed to identify consistent tumor stage-specific differences. However, the myoepithelial cell layer, present only in DCIS, is a key distinguishing and diagnostic feature. To determine the contribution of non-epithelial cells to tumor progression, we analyzed the role of myoepithelial cells and fibroblasts in the progression of in situ carcinomas using a xenograft model of human DCIS. Progression to invasion was promoted by fibroblasts, but inhibited by normal myoepithelial cells. The invasive tumor cells from these progressed lesions formed DCIS rather than invasive cancers when re-injected into naive mice. Molecular profiles of myoepithelial and epithelial cells isolated from primary normal and cancerous human breast tissue samples corroborated findings obtained in the xenograft model. These results provide the proof of principle that breast tumor progression could occur in the absence of additional genetic alterations and that tumor growth and progression could be controlled by replacement of normal myoepithelial inhibitory signals.

  15. Regulation of In Situ to Invasive Breast CarcinomaTransition

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Min; Carroll, Danielle K.; Weremowicz, Stanislawa; Chen,Haiyan; Carrasco, Daniel; Richardson, Andrea; Bissell, Mina; Violette,Shelia; Gelman, Rebecca S.; Schnitt, Stuart; Polyak, Kornelia

    2007-03-13

    The transition of ductal carcinoma in situ (DCIS) to invasive carcinoma is a key event in breast tumor progression that is poorly understood. Comparative molecular analysis of tumor epithelial cells from in situ and invasive tumors has failed to identify consistent tumor stage-specific differences. However, the myoepithelial cell layer, present only in DCIS, is a key distinguishing and diagnostic feature. To determine the contribution of non-epithelial cells to tumor progression, we analyzed the role of myoepithelial cells and fibroblasts in the progression of in situ carcinomas using a xenograft model of human DCIS. Progression to invasion was promoted by fibroblasts, but inhibited by normal myoepithelial cells. The invasive tumor cells from these progressed lesions formed DCIS rather than invasive cancers when re-injected into naive mice. Molecular profiles of myoepithelial and epithelial cells isolated from primary normal and cancerous human breast tissue samples corroborated findings obtained in the xenograft model. These results provide the proof of principle that breast tumor progression could occur in the absence of additional genetic alterations and that tumor growth and progression could be controlled by replacement of normal myoepithelial inhibitory signals.

  16. A stromal cell population in the large intestine identified by tissue factor expression that is lost during colorectal cancer progression.

    Science.gov (United States)

    Eriksson, Oskar; Asplund, Anna; Hegde, Geeta; Edqvist, Per-Henrik; Navani, Sanjay; Pontén, Fredrik; Siegbahn, Agneta

    2016-11-30

    Colorectal cancer (CRC) is a major cause of morbidity and mortality, and the composition of the tumour stroma is a strong predictor of survival in this cancer type. Tissue factor (TF) functions as the trigger of haemostasis together with its ligand coagulation factor VII/VIIa, and TF expression has been found in tumour cells of colorectal tumours. However, TF expression in the CRC tumour stroma or its relationship to patient outcome has not yet been studied. To address this question we developed and validated a specific anti-TF antibody using standardised methods within the Human Protein Atlas project. We used this antibody to investigate TF expression in normal colorectal tissue and CRC using immunofluorescence and immunohistochemistry in two patient cohorts. TF was strongly expressed in a cell population immediately adjacent to the colorectal epithelium. These TF-positive cells were ACTA2-negative but weakly vimentin-positive, defining a specific population of pericryptal sheath cells. In colorectal tumours, TF-positive sheath cells were progressively lost after the adenoma-to-carcinoma transition, demonstrating downregulation of this source of TF in CRC. Furthermore, loss of sheath cell TF was significantly associated with poor overall and disease-specific survival in rectal but not colon cancers. In conclusion, we demonstrate that TF is a marker of a specific cell population in the large intestine, which is lost during CRC progression. Our results highlight the role of the tumour stroma in this cancer type and suggest TF to be a potential prognostic biomarker in rectal cancers through the identification of pericryptal sheath cells.

  17. Interagency partnering for weed prevention--progress on development of a National Early Detection and Rapid Response System for Invasive Plants in the United States

    Science.gov (United States)

    Westbrooks, R.; Westbrooks, R.

    2011-01-01

    Over the past 50 years, experience has shown that interagency groups provide an effective forum for addressing various invasive species issues and challenges on multiple land units. However, more importantly, they can also provide a coordinated framework for early detection, reporting, identification and vouchering, rapid assessment, and rapid response to new and emerging invasive plants in the United States. Interagency collaboration maximizes the use of available expertise, resources, and authority for promoting early detection and rapid response (EDRR) as the preferred management option for addressing new and emerging invasive plants. Currently, an interagency effort is underway to develop a National EDRR System for Invasive Plants in the United States. The proposed system will include structural and informational elements. Structural elements of the system include a network of interagency partner groups to facilitate early detection and rapid response to new invasive plants, including the Federal Interagency Committee for the Management of Noxious and Exotic Weeds (FICMNEW), State Invasive Species Councils, State Early Detection and Rapid Response Coordinating Committees, State Volunteer Detection and Reporting Networks, Invasive Plant Task Forces, and Cooperative Weed Management Areas. Informational elements and products being developed include Regional Invasive Plant Atlases, and EDRR Guidelines for EDRR Volunteer Network Training, Rapid Assessment and Rapid Response, and Criteria for Selection of EDRR Species. System science and technical support elements which are provided by cooperating state and federal scientists, include EDRR guidelines, training curriculum for EDRR volunteers and agency field personnel, plant identification and vouchering, rapid assessments, as well as predictive modeling and ecological range studies for invasive plant species.

  18. Metrics for the Human Proteome Project 2016: Progress on Identifying and Characterizing the Human Proteome, Including Post-Translational Modifications.

    Science.gov (United States)

    Omenn, Gilbert S; Lane, Lydie; Lundberg, Emma K; Beavis, Ronald C; Overall, Christopher M; Deutsch, Eric W

    2016-11-04

    The HUPO Human Proteome Project (HPP) has two overall goals: (1) stepwise completion of the protein parts list-the draft human proteome including confidently identifying and characterizing at least one protein product from each protein-coding gene, with increasing emphasis on sequence variants, post-translational modifications (PTMs), and splice isoforms of those proteins; and (2) making proteomics an integrated counterpart to genomics throughout the biomedical and life sciences community. PeptideAtlas and GPMDB reanalyze all major human mass spectrometry data sets available through ProteomeXchange with standardized protocols and stringent quality filters; neXtProt curates and integrates mass spectrometry and other findings to present the most up to date authorative compendium of the human proteome. The HPP Guidelines for Mass Spectrometry Data Interpretation version 2.1 were applied to manuscripts submitted for this 2016 C-HPP-led special issue [ www.thehpp.org/guidelines ]. The Human Proteome presented as neXtProt version 2016-02 has 16,518 confident protein identifications (Protein Existence [PE] Level 1), up from 13,664 at 2012-12, 15,646 at 2013-09, and 16,491 at 2014-10. There are 485 proteins that would have been PE1 under the Guidelines v1.0 from 2012 but now have insufficient evidence due to the agreed-upon more stringent Guidelines v2.0 to reduce false positives. neXtProt and PeptideAtlas now both require two non-nested, uniquely mapping (proteotypic) peptides of at least 9 aa in length. There are 2,949 missing proteins (PE2+3+4) as the baseline for submissions for this fourth annual C-HPP special issue of Journal of Proteome Research. PeptideAtlas has 14,629 canonical (plus 1187 uncertain and 1755 redundant) entries. GPMDB has 16,190 EC4 entries, and the Human Protein Atlas has 10,475 entries with supportive evidence. neXtProt, PeptideAtlas, and GPMDB are rich resources of information about post-translational modifications (PTMs), single amino acid

  19. Quantification of circulating clonal plasma cells via multiparametric flow cytometry identifies patients with smoldering multiple myeloma at high risk of progression.

    Science.gov (United States)

    Gonsalves, W I; Rajkumar, S V; Dispenzieri, A; Dingli, D; Timm, M M; Morice, W G; Lacy, M Q; Buadi, F K; Go, R S; Leung, N; Kapoor, P; Hayman, S R; Lust, J A; Russell, S J; Zeldenrust, S R; Hwa, L; Kourelis, T V; Kyle, R A; Gertz, M A; Kumar, S K

    2017-01-01

    The presence of high numbers of circulating clonal plasma cells (cPCs) in patients with smoldering multiple myeloma (SMM), detected by a slide-based immunofluorescence assay, has been associated with a shorter time to progression (TTP) to MM. The significance of quantifying cPCs via multiparameter flow cytometry, a much more readily available diagnostic modality, in patients with SMM has not been evaluated. This study evaluated 100 patients with a known or new diagnosis of SMM who were seen at the Mayo Clinic, Rochester from January 2008 until December 2013. Patients with ⩾150 cPCs (N=9) were considered to have high number of cPCs based on the 97% specificity and 78% PPV of progression to MM within 2 years of cPC assessment. The median TTP of patients with ⩾150 cPCs was 9 months compared with not reached for patients with <150 cPCs (P<0.001). Thus, quantification of cPCs via multiparametric flow cytometry identifies patients with SMM at very high risk of progression to MM within 2 years and warrants confirmation in larger studies. In the future, this may allow reclassification of such patients as having MM requiring therapy prior to them enduring end-organ damage.

  20. A role for benzo[a]pyrene and Slug in invasive properties of fibroblast-like synoviocytes in rheumatoid arthritis: a potential molecular link between smoking and radiographic progression.

    Science.gov (United States)

    Lee, Jaejoon; Jeong, Hyemin; Park, Eun-Jung; Hwang, Ji Won; Bae, Eun-Kyung; Ahn, Joong Kyong; Ahn, Kwang-Sung; Koh, Eun-Mi; Cha, Hoon-Suk

    2013-12-01

    To investigate the effects of benzo[a]pyrene (B[a]P), a major toxic component of cigarette smoke, on the expression of Slug and to determine the effect of B[a]P/Slug on the invasive properties of rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS). The expression of Slug was measured by real-time PCR following the stimulation of FLS with different concentrations of B[a]P or EGF. The phosphorylation of the key enzymes in the signaling pathway was analyzed by western blots. Inhibitors of PI3K/Akt/mTOR pathway were used to confirm the critical pathway for Slug expression. An in vitro cell invasion assay was performed using RA FLS treated with Slug cDNA, Slug small interference RNA, or control. Slug expression increased significantly following treatment with B[a]P or EGF in a dose-dependent manner. The stimulation of FLS with B[a]P or EGF induced the phosphorylation of Akt kinase, but not in ERK, JNK and p38. The Slug mRNA expression induced by B[a]P and EGF decreased significantly following the treatment with PI3K/Akt/mTOR inhibitors. Slug overexpression using Slug cDNA upregulated the invasive function of FLS, and Slug depletion using siRNA showed the opposite effect compared with the control. In addition, the stimulation with B[a]P increased the invasive function of the control siRNA-treated FLS but not in the Slug siRNA-treated FLS. Our data showed that B[a]P regulates the invasive properties of RA FLS through Slug expression. This mechanism may provide a novel molecular link underlying the association between smoking and increased radiographic progression in RA. Copyright © 2013 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

  1. Chronic kidney disease as a risk factor for recurrence and progression in patients with primary non-muscle-invasive bladder cancer.

    Science.gov (United States)

    Kobatake, Kohei; Hayashi, Tetsutaro; Black, Peter C; Goto, Keisuke; Sentani, Kazuhiro; Kaneko, Mayumi; Yasui, Wataru; Mita, Koji; Teishima, Jun; Matsubara, Akio

    2017-08-01

    To investigate the relationship between chronic kidney disease and primary non-muscle-invasive bladder cancer. Disease outcomes were analyzed in 418 patients treated with transurethral resection for primary non-muscle-invasive bladder cancer, and were correlated to traditional risk factors as well as chronic kidney disease stage according to estimated glomerular filtration rate: ≥60 (G1-2), 45-59 (G3a) or chronic kidney disease, respectively. T1 tumor was present in 29.6% of G1-2, 43.9% of G3a and 51.4% of G3b-5 chronic kidney disease (P = 0.004). The proportion of histological grade 3 non-muscle-invasive bladder cancer was higher in G3a and G3b-5 than G1-2 (P chronic kidney disease stage was associated with worse recurrence-free (P Chronic kidney disease stage was also strongly associated with the European Association of Urology bladder cancer risk groups (P Chronic kidney disease predicts the clinical outcome of primary non-muscle-invasive bladder cancer. Adding chronic kidney disease to the conventional risk factors might increase the accuracy of risk stratification. © 2017 The Japanese Urological Association.

  2. Progress towards non-invasive diagnosis and follow-up of celiac disease in children : a prospective multicentre study to the usefulness of plasma I-FABP

    NARCIS (Netherlands)

    Adriaanse, Marlou P. M.; Mubarak, A; Riedl, R G; Ten Kate, F J W; Damoiseaux, J G M C; Buurman, Wim A.; Houwen, R H J; Vreugdenhil, A C E

    2017-01-01

    This prospective study investigates whether measurement of plasma intestinal-fatty acid binding protein (I-FABP), a sensitive marker for small intestinal epithelial damage, improves non-invasive diagnosing of celiac disease (CD), and whether I-FABP levels are useful to evaluate mucosal healing in

  3. Progressive Increase in Antimicrobial Resistance among Invasive Isolates of Haemophilus influenzae Obtained from Children Admitted to a Hospital in Kilifi, Kenya, from 1994 to 2002

    Science.gov (United States)

    Scott, J. Anthony G.; Mwarumba, Salim; Ngetsa, Caroline; Njenga, Salome; Lowe, Brett S.; Slack, Mary P. E.; Berkley, James A.; Mwangi, Isaiah; Maitland, Kathryn; English, Mike; Marsh, Kevin

    2005-01-01

    Etest susceptibilities to amoxicillin, chloramphenicol, and trimethoprim-sulfamethoxazole of 240 invasive isolates of Haemophilus influenzae cultured from children in rural Kenya were 66%, 66%, and 38%, respectively. Resistance increased markedly over 9 years and was concentrated among serotype b isolates. In Africa, the increasing cost of treating resistant infections supports economic arguments for prevention through conjugate H. influenzae type b immunization. PMID:15980390

  4. Mechanisms of Glioma Formation: Iterative Perivascular Glioma Growth and Invasion Leads to Tumor Progression, VEGF-Independent Vascularization, and Resistance to Antiangiogenic Therapy

    Directory of Open Access Journals (Sweden)

    Gregory J. Baker

    2014-07-01

    Full Text Available As glioma cells infiltrate the brain they become associated with various microanatomic brain structures such as blood vessels, white matter tracts, and brain parenchyma. How these distinct invasion patterns coordinate tumor growth and influence clinical outcomes remain poorly understood. We have investigated how perivascular growth affects glioma growth patterning and response to antiangiogenic therapy within the highly vascularized brain. Orthotopically implanted rodent and human glioma cells are shown to commonly invade and proliferate within brain perivascular space. This form of brain tumor growth and invasion is also shown to characterize de novo generated endogenous mouse brain tumors, biopsies of primary human glioblastoma (GBM, and peripheral cancer metastasis to the human brain. Perivascularly invading brain tumors become vascularized by normal brain microvessels as individual glioma cells use perivascular space as a conduit for tumor invasion. Agent-based computational modeling recapitulated biological perivascular glioma growth without the need for neoangiogenesis. We tested the requirement for neoangiogenesis in perivascular glioma by treating animals with angiogenesis inhibitors bevacizumab and DC101. These inhibitors induced the expected vessel normalization, yet failed to reduce tumor growth or improve survival of mice bearing orthotopic or endogenous gliomas while exacerbating brain tumor invasion. Our results provide compelling experimental evidence in support of the recently described failure of clinically used antiangiogenics to extend the overall survival of human GBM patients.

  5. Seven-year median time to progression with thalidomide for smoldering myeloma: partial response identifies subset requiring earlier salvage therapy for symptomatic disease

    Science.gov (United States)

    van Rhee, Frits; Shaughnessy, John D.; Epstein, Joshua; Yaccoby, Shmuel; Pineda-Roman, Mauricio; Hollmig, Klaus; Alsayed, Yazan; Hoering, Antje; Szymonifka, Jackie; Anaissie, Elias; Petty, Nathan; Kumar, Naveen S.; Srivastava, Geetika; Jenkins, Bonnie; Crowley, John; Zeldis, Jerome B.

    2008-01-01

    Smoldering multiple myeloma (SMM) is usually followed expectantly without therapy. We conducted a phase 2 trial in 76 eligible patients with SMM, combining thalidomide (THAL, 200 mg/d) with monthly pamidronate. In the first 2 years, THAL dose reduction was required in 86% and drug was discontinued in 50%. Within 4 years, 63% improved, including 25% qualifying for partial response (PR); by then, 34 patients had progressed and 17 required salvage therapy. Unexpectedly, attaining PR status was associated with a shorter time to salvage therapy for disease progression (P < .001), perhaps reflecting greater drug sensitivity of more aggressive disease. Low beta-2-microglobulin levels less than 2 mg/L were independently associated with superior overall and event-free survival. Four-year survival and event-free survival estimates of 91% and 60%, respectively, together with a median postsalvage therapy survival of more than 5 years justify the conduct of a prospective randomized clinical trial to determine the clinical value of preemptive therapy in SMM. Trial registered at http://www.clinicaltrials.gov under identifier NCT00083382. PMID:18669874

  6. Current research in perineural invasion of cholangiocarcinoma

    Directory of Open Access Journals (Sweden)

    Deng Xi-Yun

    2010-03-01

    Full Text Available Abstract Background Perineural invasion is a common path for cholangiocarcinoma (CCA metastasis, and it is highly correlated with postoperative recurrence and poor prognosis. It is often an early event in a disease that is commonly diagnosed in advanced stages, and thus it could offer a timely therapeutic and diagnostic target if better understood. This article systematically reviews the progress of CCA neural invasion-related molecules. Methods Studies were identified by searching MEDLINE and PubMed databases for articles from January 1990 to December 2009, using the keywords "cholangiocarcinoma," "perineural invasion," "nerve growth factor"(NGF, "neural cell adhesion molecule" (NCAM, "matrix metalloproteinase"(MMP, "neurotransmitter," "acetylcholine" (Ach, and "transforming growth factor" (TGF." Additional papers and book chapters were identified by a manual search of references from the key articles. Results From above we found that the molecules NGF, NCAM, MMP, Ach and TGF may have prognostic significance in, and offer clues to the mechanism of CCA neural invasion. Conclusions Cholangiocarcinoma's increasing worldwide incidence is especially poignant in view of both the lacking effective therapies, and the fact that it is commonly diagnosed in advanced stages. As CCA neural invasion often appears early, more complete characterization of its molecular pathology could lead to the identification of targets for the diagnosis and therapy of this devastating malignancy.

  7. A New Era of Minimally Invasive Surgery: Progress and Development of Major Technical Innovations in General Surgery Over the Last Decade.

    Science.gov (United States)

    Siddaiah-Subramanya, Manjunath; Tiang, Kor Woi; Nyandowe, Masimba

    2017-10-01

    Minimally invasive surgery (MIS) continues to play an important role in general surgery as an alternative to traditional open surgery as well as traditional laparoscopic techniques. Since the 1980s, technological advancement and innovation have seen surgical techniques in MIS rapidly grow as it is viewed as more desirable. MIS, which includes natural orifice transluminal endoscopic surgery (NOTES) and single-incision laparoscopic surgery (SILS), is less invasive and has better cosmetic results. The technological growth and adoption of NOTES and SILS by clinicians in the last decade has however not been uniform. We look at the differences in new developments and advancement in the different techniques in the last 10 years. We also aim to explain these differences as well as the implications in general surgery for the future.

  8. Do Standardised Prognostic Algorithms Reflect Local Practice? Application of EORTC Risk Tables for Non-Muscle Invasive (pTa/pT1 Bladder Cancer Recurrence and Progression in a Local Cohort

    Directory of Open Access Journals (Sweden)

    Rajiv Pillai

    2011-01-01

    Full Text Available A risk calculator algorithm to allow prediction of probabilities of 1- and 5-year recurrence and progression rates in individuals with pTa/pT1 bladder cancer has been proposed by the European Organisation for Research and Treatment of Cancer (EORTC and was incorporated into the European Association of Urology guidelines in 2006. We attempted to validate this algorithm in a cohort of patients with known outcome. Prognostic data were collected from a consecutively presenting cohort of 109 patients with non-muscle invasive (pTa/pT1 transitional cell cancer (TCC at a single institution between 1983 and 1985. Using the same statistical models as in the EORTC original paper, predicted probabilities of 1- and 5-year recurrence and progression were calculated. Patients were divided into four risk groups for recurrence (Ir-IVr and progression (Ip-IVp, respectively, using six prognostic criteria. These were then compared to the probabilities predicted in the EORTC algorithm. The predicted 1- and 5-year probabilities of recurrence were significantly higher in the study population as compared to the original EORTC algorithm for all four risk groups. The predicted 1-year probabilities for progression in groups Ip/IIIp and at 5-years for groups Ip/IIp were in accordance with the original algorithm, but were higher for the other progression groups. The concordance for the model of prediction using the study group for recurrence at 1 and 5 years was 62 and 63%, respectively, and for progression was 65 and 67, respectively. We were unable to validate the proposed algorithm in our group of patients. Although our study has limitations that prevent firm conclusions on the validity of the algorithm, it does expose some of the drawbacks of standardised nomograms when applied to local clinical practice.

  9. Cell invasion through basement membrane

    OpenAIRE

    Morrissey, Meghan A; Hagedorn, Elliott J; Sherwood, David R

    2013-01-01

    Cell invasion through basement membrane is an essential part of normal development and physiology, and occurs during the pathological progression of human inflammatory diseases and cancer. F-actin-rich membrane protrusions, called invadopodia, have been hypothesized to be the “drill bits” of invasive cells, mediating invasion through the dense, highly cross-linked basement membrane matrix. Though studied in vitro for over 30 y, invadopodia function in vivo has remained elusive. We have recent...

  10. Invasive Species

    Science.gov (United States)

    Invasive species have significantly changed the Great Lakes ecosystem. An invasive species is a plant or animal that is not native to an ecosystem, and whose introduction is likely to cause economic, human health, or environmental damage.

  11. Non-invasive measurements of granular flows by magnetic resonance imaging. Technical progress report for the quarter ending December 31, 1992

    Energy Technology Data Exchange (ETDEWEB)

    Nakagawa, M.; Altobelli, S.A.; Caprihan, A.; Fukushima, E.; Jeong, E.K.

    1993-01-20

    Magnetic Resonance Imaging (MRI) was used to measure granular-flow in a partially filled, steadily rotating, long, horizontal cylinder. This non-invasive technique can yield statistically averaged two-dimensional concentrations and velocity profiles anywhere in the flow of suitable granular materials. First, rigid body motion of a cylinder fill with granular material was studied to confirm the validity of this method. Then, the density variation of the flowing layer where particles collide and dilate, and the depth of the flowing layer and the flow velocity profile were obtained as a function of the cylinder rotation rate.

  12. Copy Number Analysis of 24 Oncogenes: MDM4 Identified as a Putative Marker for Low Recurrence Risk in Non Muscle Invasive Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Samanta Salvi

    2014-07-01

    Full Text Available Patients with non-muscle invasive bladder cancer (NMIBC generally have a high risk of relapsing locally after primary tumor resection. The search for new predictive markers of local recurrence thus represents an important goal for the management of this disease. We studied the copy number variations (CNVs of 24 oncogenes (MDM4, MYCN, ALK, PDGFRA, KIT, KDR, DHFR, EGFR, MET, SMO, FGFR1, MYC, ABL1, RET, CCND1, CCND2, CDK4, MDM2, AURKB, ERBB2, TOP2A, AURKA, AR and BRAF using multiplex ligation probe amplification technique to verify their role as predictive markers of recurrence. Formalin-fixed paraffin-embedded tissue samples from 43 patients who underwent transurethral resection of the bladder (TURB were used; 23 patients had relapsed and 20 were disease-free after 5 years. Amplification frequencies were analyzed for all genes and MDM4 was the only gene that showed significantly higher amplification in non recurrent patients than in recurrent ones (0.65 vs. 0.3; Fisher’s test p = 0.023. Recurrence-free survival analysis confirmed the predictive role of MDM4 (log-rank test p = 0.041. Our preliminary results indicate a putative role for the MDM4 gene in predicting local recurrence of bladder cancer. Confirmation of this hypothesis is needed in a larger cohort of NMIBC patients.

  13. A panel of prognostic protein markers for progression in non-muscle invasive bladder cancer - a multicenter tissue microarray validation study

    DEFF Research Database (Denmark)

    Fristrup, Niels; Birkenkamp-Demtröder, Karin; Ulhøi, Benedicte Parm

    2012-01-01

    Bladder cancer is the fifth most common cancer in the Western world. The histopathological parameters used in the clinic cannot precisely predict the individual disease course. Bladder cancer patients are therefore monitored thoroughly for disease recurrence and progression by urine and cystoscop...

  14. Motivation and Strategies for Implementing Digital Object Identifiers (DOIs at NCAR’s Earth Observing Laboratory – Past Progress and Future Collaborations

    Directory of Open Access Journals (Sweden)

    Janine Aquino

    2017-03-01

    Full Text Available In an effort to lead our community in following modern data citation practices by formally citing data used in published research and implementing standards to facilitate reproducible research results and data, while also producing meaningful metrics that help assess the impact of our services, the National Center for Atmospheric Research (NCAR Earth Observing Laboratory (EOL has implemented the use of Digital Object Identifiers (DOIs (DataCite 2017 for both physical objects (e.g., research platforms and instruments and datasets. We discuss why this work is important and timely, and review the development of guidelines for the use of DOIs at EOL by focusing on how decisions were made. We discuss progress in assigning DOIs to physical objects and datasets, summarize plans to cite software, describe a current collaboration to develop community tools to display citations on websites, and touch on future plans to cite workflows that document dataset processing and quality control. Finally, we will review the status of efforts to engage our scientific community in the process of using DOIs in their research publications.

  15. SCOPE-mTL: A non-invasive tool for identifying and lateralizing mesial temporal lobe seizures prior to scalp EEG ictal onset.

    Science.gov (United States)

    Lam, Alice D; Maus, Douglas; Zafar, Sahar F; Cole, Andrew J; Cash, Sydney S

    2017-09-01

    In mesial temporal lobe (mTL) epilepsy, seizure onset can precede the appearance of a scalp EEG ictal pattern by many seconds. The ability to identify this early, occult mTL seizure activity could improve lateralization and localization of mTL seizures on scalp EEG. Using scalp EEG spectral features and machine learning approaches on a dataset of combined scalp EEG and foramen ovale electrode recordings in patients with mTL epilepsy, we developed an algorithm, SCOPE-mTL, to detect and lateralize early, occult mTL seizure activity, prior to the appearance of a scalp EEG ictal pattern. Using SCOPE-mTL, 73% of seizures with occult mTL onset were identified as such, and no seizures that lacked an occult mTL onset were identified as having one. Predicted mTL seizure onset times were highly correlated with actual mTL seizure onset times (r=0.69). 50% of seizures with early mTL onset were lateralizable prior to scalp ictal onset, with 94% accuracy. SCOPE-mTL can identify and lateralize mTL seizures prior to scalp EEG ictal onset, with high sensitivity, specificity, and accuracy. Quantitative analysis of scalp EEG can provide important information about mTL seizures, even in the absence of a visible scalp EEG ictal correlate. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

  16. A Minimally Invasive Method for Sampling Nest and Roost Cavities for Fungi: a Novel Approach to Identify the Fungi Associated with Cavity-Nesting Birds

    Science.gov (United States)

    Michelle A. Jusino; Daniel Lindner; John K. Cianchetti; Adam T. Grisé; Nicholas J. Brazee; Jeffrey R. Walters

    2014-01-01

    Relationships among cavity-nesting birds, trees, and wood decay fungi pose interesting management challenges and research questions in many systems. Ornithologists need to understand the relationships between cavity-nesting birds and fungi in order to understand the habitat requirements of these birds. Typically, researchers rely on fruiting body surveys to identify...

  17. Invasive and Ultrasound Based Monitoring of the Intracranial Pressure in an Experimental Model of Epidural Hematoma Progressing towards Brain Tamponade on Rabbits

    Directory of Open Access Journals (Sweden)

    Konstantinos Kasapas

    2014-01-01

    Full Text Available Introduction. An experimental epidural hematoma model was used to study the relation of ultrasound indices, namely, transcranial color-coded-Doppler (TCCD derived pulsatility index (PI, optic nerve sheath diameter (ONSD, and pupil constriction velocity (V which was derived from a consensual sonographic pupillary light reflex (PLR test with invasive intracranial pressure (ICP measurements. Material and Methods. Twenty rabbits participated in the study. An intraparenchymal ICP catheter and a 5F Swan-Ganz catheter (SG for the hematoma reproduction were used. We successively introduced 0.1 mL increments of autologous blood into the SG until the Cushing reaction occurred. Synchronous ICP and ultrasound measurements were performed accordingly. Results. A constant increase of PI and ONSD and a decrease of V values were observed with increased ICP values. The relationship between the ultrasound variables and ICP was exponential; thus curved prediction equations of ICP were used. PI, ONSD, and V were significantly correlated with ICP (r2=0.84±0.076, r2=0.62±0.119, and r2=0.78±0.09, resp. (all P<0.001. Conclusion. Although statistically significant prediction models of ICP were derived from ultrasound indices, the exponential relationship between the parameters underpins that results should be interpreted with caution and in the current experimental context.

  18. Genome-Wide siRNA Screen Identifies Complementary Signaling Pathways Involved in Listeria Infection and Reveals Different Actin Nucleation Mechanisms during Listeria Cell Invasion and Actin Comet Tail Formation

    Science.gov (United States)

    Kühbacher, Andreas; Emmenlauer, Mario; Rämo, Pauli; Kafai, Natasha; Dehio, Christoph

    2015-01-01

    ABSTRACT Listeria monocytogenes enters nonphagocytic cells by a receptor-mediated mechanism that is dependent on a clathrin-based molecular machinery and actin rearrangements. Bacterial intra- and intercellular movements are also actin dependent and rely on the actin nucleating Arp2/3 complex, which is activated by host-derived nucleation-promoting factors downstream of the cell receptor Met during entry and by the bacterial nucleation-promoting factor ActA during comet tail formation. By genome-wide small interfering RNA (siRNA) screening for host factors involved in bacterial infection, we identified diverse cellular signaling networks and protein complexes that support or limit these processes. In addition, we could precise previously described molecular pathways involved in Listeria invasion. In particular our results show that the requirements for actin nucleators during Listeria entry and actin comet tail formation are different. Knockdown of several actin nucleators, including SPIRE2, reduced bacterial invasion while not affecting the generation of comet tails. Most interestingly, we observed that in contrast to our expectations, not all of the seven subunits of the Arp2/3 complex are required for Listeria entry into cells or actin tail formation and that the subunit requirements for each of these processes differ, highlighting a previously unsuspected versatility in Arp2/3 complex composition and function. PMID:25991686

  19. Non-invasive ventilation for cystic fibrosis.

    Science.gov (United States)

    Moran, Fidelma; Bradley, Judy M; Piper, Amanda J

    2017-02-20

    Non-invasive ventilation may be a means to temporarily reverse or slow the progression of respiratory failure in cystic fibrosis by providing ventilatory support and avoiding tracheal intubation. Using non-invasive ventilation, in the appropriate situation or individuals, can improve lung mechanics through increasing airflow and gas exchange and decreasing the work of breathing. Non-invasive ventilation thus acts as an external respiratory muscle. This is an update of a previously published review. To compare the effect of non-invasive ventilation versus no non-invasive ventilation in people with cystic fibrosis for airway clearance, during sleep and during exercise. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearching relevant journals and abstract books of conference proceedings. We searched the reference lists of each trial for additional publications possibly containing other trials.Most recent search: 08 August 2016. Randomised controlled trials comparing a form of pressure preset or volume preset non-invasive ventilation to no non-invasive ventilation used for airway clearance or during sleep or exercise in people with acute or chronic respiratory failure in cystic fibrosis. Three reviewers independently assessed trials for inclusion criteria and methodological quality, and extracted data. Ten trials met the inclusion criteria with a total of 191 participants. Seven trials evaluated single treatment sessions, one evaluated a two-week intervention, one evaluated a six-week intervention and one a three-month intervention. It is only possible to blind trials of airway clearance and overnight ventilatory support to the outcome assessors. In most of the trials we judged there was an unclear risk of bias with regards to blinding due to inadequate descriptions. The six-week trial was the only one judged to have a low risk of bias for all

  20. Orbital exenteration for invasive skin tumours.

    Science.gov (United States)

    Tyers, A G

    2006-10-01

    Orbital exenteration aims at local control of disease invading the orbit that is potentially fatal or relentlessly progressive. Of all exenterations presenting to ophthalmologists, 40-50% are required for tumours in the eyelid or periocular skin. 99% of these are basal cell carcinomas and 4-6% each are squamous cell carcinomas or sebaceous gland carcinomas. Orbital invasion results in progressive fixation of the tumour to bone and reduced ocular motility. Perineural invasion of branches of the trigeminal nerve leads to numbness or pain, and that the facial nerve, to weakness. Biopsy identifies the cell type and the presence of perineural invasion. CT and MRI scanning help in the assessment of tumour spread within the orbit. Management should be in collaboration with an oncologist. Exenteration may be total-the removal of all orbital contents-or lid-sparing if the tumour is placed posteriorly. The socket may be allowed to heal by granulation or lined with a split skin graft or local flap. Complications may be seen following 20-25% of exenterations and include fistulae, tissue necrosis, exposed bone, and infection. Incomplete clearance of tumours occurs in about 38% of total exenterations and 17% of subtotal. The overall 5-year survival is 55-65%, but significantly worse if there was perineural spread. Facial prostheses may be mounted on glasses or secured with tissue glue or osseointegrated implants. Excellent cosmetic results can be achieved but many patients prefer to wear a patch.

  1. HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP): A comparative study to identify factors that influence disease progression.

    Science.gov (United States)

    Matsuura, Eiji; Nozuma, Satoshi; Tashiro, Yuichi; Kubota, Ryuji; Izumo, Shuji; Takashima, Hiroshi

    2016-12-15

    HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) can progress slowly or rapidly even though a set of symptoms such as spastic paraparesis with pathological reflexes and sweating loss of the lower extremities are commonly observed in patients. Although most of the patients are thought to be infected to HTLV-1 from their mothers by breast feeding, symptoms of HAM/TSP typically manifest in patients later in life (50-60years old in age) and also with a higher prevalence of women to men at a ratio of approximately 3:1. Probability of developing HAM/TSP and how fast an individual's disease may progress from the time of diagnosis could be multifactorial. We reviewed the records of 150 patients with HAM/TSP admitted to Kagoshima University Hospital between 2002 and 2014. Laboratory data of cerebrospinal fluid and serum and the clinical measurements including age, age of disease onset, progression rate, duration of illness, initial symptoms, Osame's Motor Disability Score were evaluated. Rapid disease progression of the disease was defined by deterioration of motor disability by >3 grades within 2years. Of 150 HAM/TSP patients in our cohort, 114 cases (76%) were females. Patients presenting with rapid disease progression are approximately 15years older at the age of onset than those with a protracted disease course, and have increased number of cell, and elevated levels of protein as well as anti-HTLV-1 antibody titer in the CSF, suggesting a more active inflammatory process. There is no significant difference in the average values of clinical and laboratory parameters between the sexes. Furthermore, there is no apparent correlation between rate of disease progression and gender. Our results suggest that age and virus mediated inflammation are correlated with disease phenotypes while additional factors such as host or HTLV-1 genetics and gender may influence disease susceptibility. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights

  2. Non-invasive imaging provides spatiotemporal information on disease progression and response to therapy in a murine model of multiple myeloma.

    Directory of Open Access Journals (Sweden)

    Simone S Riedel

    Full Text Available Multiple myeloma (MM is a B-cell malignancy, where malignant plasma cells clonally expand in the bone marrow of older people, causing significant morbidity and mortality. Typical clinical symptoms include increased serum calcium levels, renal insufficiency, anemia, and bone lesions. With standard therapies, MM remains incurable; therefore, the development of new drugs or immune cell-based therapies is desirable. To advance the goal of finding a more effective treatment for MM, we aimed to develop a reliable preclinical MM mouse model applying sensitive and reproducible methods for monitoring of tumor growth and metastasis in response to therapy.A mouse model was created by intravenously injecting bone marrow-homing mouse myeloma cells (MOPC-315.BM that expressed luciferase into BALB/c wild type mice. The luciferase in the myeloma cells allowed in vivo tracking before and after melphalan treatment with bioluminescence imaging (BLI. Homing of MOPC-315.BM luciferase+ myeloma cells to specific tissues was examined by flow cytometry. Idiotype-specific myeloma protein serum levels were measured by ELISA. In vivo measurements were validated with histopathology.Strong bone marrow tropism and subsequent dissemination of MOPC-315.BM luciferase(+ cells in vivo closely mimicked the human disease. In vivo BLI and later histopathological analysis revealed that 12 days of melphalan treatment slowed tumor progression and reduced MM dissemination compared to untreated controls. MOPC-315.BM luciferase(+ cells expressed CXCR4 and high levels of CD44 and α4β1 in vitro which could explain the strong bone marrow tropism. The results showed that MOPC-315.BM cells dynamically regulated homing receptor expression and depended on interactions with surrounding cells.This study described a novel MM mouse model that facilitated convenient, reliable, and sensitive tracking of myeloma cells with whole body BLI in living animals. This model is highly suitable for monitoring

  3. The risk of establishment of aquatic invasive species: joining invasibility and propagule pressure.

    Science.gov (United States)

    Leung, Brian; Mandrak, Nicholas E

    2007-10-22

    Invasive species are increasingly becoming a policy priority. This has spurred researchers and managers to try to estimate the risk of invasion. Conceptually, invasions are dependent both on the receiving environment (invasibility) and on the ability to reach these new areas (propagule pressure). However, analyses of risk typically examine only one or the other. Here, we develop and apply a joint model of invasion risk that simultaneously incorporates invasibility and propagule pressure. We present arguments that the behaviour of these two elements of risk differs substantially--propagule pressure is a function of time, whereas invasibility is not--and therefore have different management implications. Further, we use the well-studied zebra mussel (Dreissena polymorpha) to contrast predictions made using the joint model to those made by separate invasibility and propagule pressure models. We show that predictions of invasion progress as well as of the long-term invasion pattern are strongly affected by using a joint model.

  4. Predictive Factors for Time to Progression after Hyperthermic Mitomycin C Treatment for High-Risk Non-Muscle Invasive Urothelial Carcinoma of the Bladder: An Observational Cohort Study of 97 Patients.

    Science.gov (United States)

    Sooriakumaran, Prasanna; Chiocchia, Virginia; Dutton, Susan; Pai, Aakash; Ayres, Benjamin E; Le Roux, Pieter; Swinn, Michael; Bailey, Michael; Perry, Matthew J A; Issa, Rami

    2016-01-01

    Hyperthermic mitomycin (HM) is a novel treatment modality for selected patients with high-risk non-muscle invasive bladder cancer (NMIBC). We sought to determine predictors of response to this therapy. A longitudinal, cohort study of 97 patients with high-risk NMIBC treated with ≥4 HM instillations on a prophylactic schedule was conducted. The primary outcome was time-to-progression survival; secondary outcomes were overall survival, cancer-specific survival, and adverse events. Descriptive statistics, Kaplan-Meier survival analyses, Cox proportional hazards modelling, and univariate and multivariable regression were performed. The presence of initial complete response (CR; no evidence of disease at first check video-cystoscopy and urine cytology) post-HM treatment was an independent predictor of good response to HM. Female patients and those without carcinoma in situ (CIS) also appeared to respond better to the intervention. The overall bladder preservation rate at a median of 27 months was 81.4%; 17/97 (17.5%) patients died during the course of the study. High-risk NMIBC patients can be safely treated with HM and have good oncological outcome. However, those without an initial CR have a poor prognosis and should be counselled towards adopting other treatment methodologies such as cystectomy. Female gender and lack of CIS may be good prognostic indicators for response to HM. © 2015 S. Karger AG, Basel.

  5. Fibrogenesis assessed by serological type III collagen formation identifies patients with progressive liver fibrosis and responders to a potential antifibrotic therapy

    DEFF Research Database (Denmark)

    Karsdal, Morten A; Henriksen, Kim; Nielsen, Mette Juul

    2016-01-01

    trial of the glitazone farglitazar in patients with advanced hepatitis C, with matched follow-up liver biopsies, and from a phase III study of balaglitazone in patients with late-stage Type 2 diabetes (BALLET study) were analyzed for serological Pro-C3 levels in conjunction with other disease parameters....... In the farglitazar study, a predefined cutoff value for Pro-C3 as a selection criterion led to the identification of subjects who 1) progressed by histological scores and 2) responded to therapy, as documented by attenuated fibrosis in liver biopsies. In the BALLET trial, subjects with the highest tertile of Pro-C3...

  6. Cell invasion through basement membrane

    Science.gov (United States)

    Morrissey, Meghan A; Hagedorn, Elliott J; Sherwood, David R

    2013-01-01

    Cell invasion through basement membrane is an essential part of normal development and physiology, and occurs during the pathological progression of human inflammatory diseases and cancer. F-actin-rich membrane protrusions, called invadopodia, have been hypothesized to be the “drill bits” of invasive cells, mediating invasion through the dense, highly cross-linked basement membrane matrix. Though studied in vitro for over 30 y, invadopodia function in vivo has remained elusive. We have recently discovered that invadopodia breach basement membrane during anchor cell invasion in C. elegans, a genetically and visually tractable in vivo invasion event. Further, we found that the netrin receptor DCC localizes to the initial site of basement membrane breach and directs invasion through a single gap in the matrix. In this commentary, we examine how the dynamics and structure of AC-invadopodia compare with in vitro invadopodia and how the netrin receptor guides invasion through a single basement membrane breach. We end with a discussion of our surprising result that the anchor cell pushes the basement membrane aside, instead of completely dissolving it through proteolysis, and provide some ideas for how proteases and physical displacement may work together to ensure efficient and robust invasion. PMID:24778942

  7. High-risk nonmuscle invasive bladder cancer: definition and epidemiology.

    Science.gov (United States)

    Porten, Sima P; Cooperberg, Matthew R

    2012-09-01

    Nonmuscle invasive bladder cancer represents a large majority of patients diagnosed with this disease. Precise definition and risk stratification are paramount in this group as high-risk patients have higher rates of progression and mortality and may benefit from early identification and aggressive treatment. The mainstay definitions of high-risk nonmuscle invasive bladder cancer are based on grade and stage. Recently, efforts have been made to incorporate other clinical variables into multivariate risk assessment tools and nomograms to predict disease behavior and guide management. Variant histology and molecular biomarkers are being explored as tools to refine risk stratification; however, results are still preliminary and need validation. Future research should concentrate on ways to better risk-stratify patients and identify early those that are most likely to recur and progress quickly. Topics of focus should be on better multivariate risk assessment tools and nomograms providing continuous scales and incorporating molecular markers with validation in large multi-institutional cohorts.

  8. Uncharismatic Invasives

    Directory of Open Access Journals (Sweden)

    Clark, Jonathan L.

    2015-05-01

    Full Text Available Although philosophers have examined the ethics of invasive species management, there has been little research approaching this topic from a descriptive, ethnographic perspective. In this article I examine how invasive species managers think about the moral status of the animals they seek to manage. I do so through a case study of Oregon’s efforts to manage the invasive species that are rafting across the Pacific attached to tsunami debris in the wake of the Japanese tsunami of 2011. Focusing on the state’s response to a dock that washed ashore on Agate Beach with various marine invertebrates attached to it, I argue that these animals’ position on two intersecting scales of moral worth—the sociozoologic scale and the phylogenetic scale—rendered them unworthy of moral consideration.

  9. Mechanisms Regulating Glioma Invasion

    Science.gov (United States)

    Paw, Ivy; Carpenter, Richard C.; Watabe, Kounosuke; Debinski, Waldemar; Lo, Hui-Wen

    2015-01-01

    Glioblastoma (GBM) is the most aggressive, deadliest, and most common brain malignancy in adults. Despite the advances made in surgical techniques, radiotherapy and chemotherapy, the median survival for GBM patients has remained at a mere 14 months. GBM poses several unique challenges to currently available treatments for the disease. For example, GBM cells have the propensity to aggressively infiltrate/invade into the normal brain tissues and along the vascular tracks, which prevents complete resection of all malignant cells and limits the effect of localized radiotherapy while sparing normal tissue. Although anti-angiogenic treatment exerts anti-edematic effect in GBM, unfortunately, tumors progress with acquired increased invasiveness. Therefore, it is an important task to gain a deeper understanding of the intrinsic and post-treatment invasive phenotypes of GBM in hopes that the gained knowledge would lead to novel GBM treatments that are more effective and less toxic. This review will give an overview of some of the signaling pathways that have been shown to positively and negatively regulate GBM invasion, including, the PI3K/Akt, Wnt, sonic hedgehog-GLI1, and microRNAs. The review will also discuss several approaches to cancer therapies potentially altering GBM invasiveness. PMID:25796440

  10. Progress in the Legitimacy of Business and Management Education Research: Rejoinder to "Identifying Research Topic Development in Business and Management Education Research Using Legitimation Code Theory"

    Science.gov (United States)

    Bacon, Donald R.

    2016-01-01

    In this rejoinder to "Identifying Research Topic Development in Business and Management Education Research Using Legitimation Code Theory," published in the "Journal of Management Education," Dec 2016 (see EJ1118407), Donald R. Bacon discusses the similarities between Arbaugh et al.'s (2016) findings and the scholarship…

  11. Optic nerve invasion of uveal melanoma

    DEFF Research Database (Denmark)

    Lindegaard, Jens; Isager, Peter; Prause, Jan Ulrik

    2007-01-01

    The aim of the study was to identify the histopathological characteristics associated with the invasion of the optic nerve of uveal melanoma and to evaluate the association between invasion of the optic nerve and survival. In order to achieve this, all uveal melanomas with optic nerve invasion...... in Denmark between 1942 and 2001 were reviewed (n=157). Histopathological characteristics and depth of optic nerve invasion were recorded. The material was compared with a control material from the same period consisting of 85 cases randomly drawn from all choroidal/ciliary body melanomas without optic nerve...... invasion. Prelaminar/laminar optic nerve invasion was in multivariate analysis associated with focal retinal invasion, neovascularization of the chamber angle, and scleral invasion. Postlaminar invasion was further associated with non-spindle cell type and rupture of the inner limiting membrane...

  12. Label-Free Protein-RNA Interactome Analysis Identifies Khsrp Signaling Downstream of the p38/Mk2 Kinase Complex as a Critical Modulator of Cell Cycle Progression.

    Directory of Open Access Journals (Sweden)

    Jorge Boucas

    Full Text Available Growing evidence suggests a key role for RNA binding proteins (RBPs in genome stability programs. Additionally, recent developments in RNA sequencing technologies, as well as mass-spectrometry techniques, have greatly expanded our knowledge on protein-RNA interactions. We here use full transcriptome sequencing and label-free LC/MS/MS to identify global changes in protein-RNA interactions in response to etoposide-induced genotoxic stress. We show that RBPs have distinct binding patterns in response to genotoxic stress and that inactivation of the RBP regulator module, p38/MK2, can affect the entire spectrum of protein-RNA interactions that take place in response to stress. In addition to validating the role of known RBPs like Srsf1, Srsf2, Elavl1 in the genotoxic stress response, we add a new collection of RBPs to the DNA damage response. We identify Khsrp as a highly regulated RBP in response to genotoxic stress and further validate its role as a driver of the G(1/S transition through the suppression of Cdkn1a(P21 transcripts. Finally, we identify KHSRP as an indicator of overall survival, as well as disease free survival in glioblastoma multiforme.

  13. Portraits of breast cancer progression

    Directory of Open Access Journals (Sweden)

    Ganesan Shridar

    2007-08-01

    Full Text Available Abstract Background Clustering analysis of microarray data is often criticized for giving ambiguous results because of sensitivity to data perturbation or clustering techniques used. In this paper, we describe a new method based on principal component analysis and ensemble consensus clustering that avoids these problems. Results We illustrate the method on a public microarray dataset from 36 breast cancer patients of whom 31 were diagnosed with at least two of three pathological stages of disease (atypical ductal hyperplasia (ADH, ductal carcinoma in situ (DCIS and invasive ductal carcinoma (IDC. Our method identifies an optimum set of genes and divides the samples into stable clusters which correlate with clinical classification into Luminal, Basal-like and Her2+ subtypes. Our analysis reveals a hierarchical portrait of breast cancer progression and identifies genes and pathways for each stage, grade and subtype. An intriguing observation is that the disease phenotype is distinguishable in ADH and progresses along distinct pathways for each subtype. The genetic signature for disease heterogeneity across subtypes is greater than the heterogeneity of progression from DCIS to IDC within a subtype, suggesting that the disease subtypes have distinct progression pathways. Our method identifies six disease subtype and one normal clusters. The first split separates the normal samples from the cancer samples. Next, the cancer cluster splits into low grade (pathological grades 1 and 2 and high grade (pathological grades 2 and 3 while the normal cluster is unchanged. Further, the low grade cluster splits into two subclusters and the high grade cluster into four. The final six disease clusters are mapped into one Luminal A, three Luminal B, one Basal-like and one Her2+. Conclusion We confirm that the cancer phenotype can be identified in early stage because the genes altered in this stage progressively alter further as the disease progresses through DCIS

  14. Targeting N-glycan cryptic sugar moieties for broad-spectrum virus neutralization: progress in identifying conserved molecular targets in viruses of distinct phylogenetic origins.

    Science.gov (United States)

    Wang, Denong; Tang, Jin; Tang, Jiulai; Wang, Lai-Xi

    2015-03-12

    Identifying molecular targets for eliciting broadly virus-neutralizing antibodies is one of the key steps toward development of vaccines against emerging viral pathogens. Owing to genomic and somatic diversities among viral species, identifying protein targets for broad-spectrum virus neutralization is highly challenging even for the same virus, such as HIV-1. However, viruses rely on host glycosylation machineries to synthesize and express glycans and, thereby, may display common carbohydrate moieties. Thus, exploring glycan-binding profiles of broad-spectrum virus-neutralizing agents may provide key information to uncover the carbohydrate-based virus-neutralizing epitopes. In this study, we characterized two broadly HIV-neutralizing agents, human monoclonal antibody 2G12 and Galanthus nivalis lectin (GNA), for their viral targeting activities. Although these agents were known to be specific for oligomannosyl antigens, they differ strikingly in virus-binding activities. The former is HIV-1 specific; the latter is broadly reactive and is able to neutralize viruses of distinct phylogenetic origins, such as HIV-1, severe acute respiratory syndrome coronavirus (SARS-CoV), and human cytomegalovirus (HCMV). In carbohydrate microarray analyses, we explored the molecular basis underlying the striking differences in the spectrum of anti-virus activities of the two probes. Unlike 2G12, which is strictly specific for the high-density Man9GlcNAc2Asn (Man9)-clusters, GNA recognizes a number of N-glycan cryptic sugar moieties. These include not only the known oligomannosyl antigens but also previously unrecognized tri-antennary or multi-valent GlcNAc-terminating N-glycan epitopes (Tri/m-Gn). These findings highlight the potential of N-glycan cryptic sugar moieties as conserved targets for broad-spectrum virus neutralization and suggest the GNA-model of glycan-binding warrants focused investigation.

  15. Targeting N-Glycan Cryptic Sugar Moieties for Broad-Spectrum Virus Neutralization: Progress in Identifying Conserved Molecular Targets in Viruses of Distinct Phylogenetic Origins

    Directory of Open Access Journals (Sweden)

    Denong Wang

    2015-03-01

    Full Text Available Identifying molecular targets for eliciting broadly virus-neutralizing antibodies is one of the key steps toward development of vaccines against emerging viral pathogens. Owing to genomic and somatic diversities among viral species, identifying protein targets for broad-spectrum virus neutralization is highly challenging even for the same virus, such as HIV-1. However, viruses rely on host glycosylation machineries to synthesize and express glycans and, thereby, may display common carbohydrate moieties. Thus, exploring glycan-binding profiles of broad-spectrum virus-neutralizing agents may provide key information to uncover the carbohydrate-based virus-neutralizing epitopes. In this study, we characterized two broadly HIV-neutralizing agents, human monoclonal antibody 2G12 and Galanthus nivalis lectin (GNA, for their viral targeting activities. Although these agents were known to be specific for oligomannosyl antigens, they differ strikingly in virus-binding activities. The former is HIV-1 specific; the latter is broadly reactive and is able to neutralize viruses of distinct phylogenetic origins, such as HIV-1, severe acute respiratory syndrome coronavirus (SARS-CoV, and human cytomegalovirus (HCMV. In carbohydrate microarray analyses, we explored the molecular basis underlying the striking differences in the spectrum of anti-virus activities of the two probes. Unlike 2G12, which is strictly specific for the high-density Man9GlcNAc2Asn (Man9-clusters, GNA recognizes a number of N-glycan cryptic sugar moieties. These include not only the known oligomannosyl antigens but also previously unrecognized tri-antennary or multi-valent GlcNAc-terminating N-glycan epitopes (Tri/m-Gn. These findings highlight the potential of N-glycan cryptic sugar moieties as conserved targets for broad-spectrum virus neutralization and suggest the GNA-model of glycan-binding warrants focused investigation.

  16. Complex multi-block analysis identifies new immunologic and genetic disease progression patterns associated with the residual β-cell function 1 year after diagnosis of type 1 diabetes

    DEFF Research Database (Denmark)

    Andersen, Marie Louise Max; Rasmussen, Morten Arendt; Pörksen, Sven

    2013-01-01

    The purpose of the present study is to explore the progression of type 1 diabetes (T1D) in Danish children 12 months after diagnosis using Latent Factor Modelling. We include three data blocks of dynamic paraclinical biomarkers, baseline clinical characteristics and genetic profiles of diabetes...... related SNPs in the analyses. This method identified a model explaining 21.6% of the total variation in the data set. The model consists of two components: (1) A pattern of declining residual β-cell function positively associated with young age, presence of diabetic ketoacidosis and long duration...

  17. Keratinocytes drive melanoma invasion in a reconstructed skin model.

    NARCIS (Netherlands)

    Kilsdonk, J.W.J. van; Bergers, M.; Kempen, L.C.L.T. van; Schalkwijk, J.; Swart, G.W.

    2010-01-01

    Melanoma progression is a multistep progression from a common melanocytic nevus through the radial growth phase, the invasive vertical growth phase finally leading to metastatic spread into distant organs. Migration and invasion of tumor cells requires secretion of proteases to facilitate remodeling

  18. Salvage external beam radiotherapy for local recurrence without systemic progression or prostate specific antigen recurrence of prostate cancer after initial hormonal therapy. Is it possible to identify patients likely to have good treatment outcomes?

    International Nuclear Information System (INIS)

    Kurokawa, Kohei; Ito, Kazuto; Suzuki, Kazuhiro; Ono, Yoshihiro; Yamamoto, Takumi; Akimoto, Tetsuo; Yamanaka, Hidetoshi

    2002-01-01

    We attempted to identify factors that predict the outcomes of salvage external beam radiotherapy (sEBRT) in patients who showed local recurrence without systemic progression or isolated prostate specific antigen (PSA) recurrence after initial hormonal therapy. The subjects were 33 patients who were diagnosed as having local recurrence without systemic progression (30 cases) or isolated PSA recurrence (three cases). Of these patients, those with continuously decreasing PSA levels, which were 1.0 ng/ml or less 1-1.5 years after sEBRT, were regarded as good responders (GR) whereas the remaining patients were regarded as poor responders (nGR). Survival rates in these patients and factors that distinguish GR from nGR were evaluated retrospectively. The cancer-specific 10-year survival rate was 82.4% in the 33 patients, 100% in the 21 GR patients and 55% in the 12 nGR patients (P 7.0 months, with a sensitivity of 95.2% (20/21), a specificity of 100% and an accuracy of 97.0%. Good responses to sEBRT can be expected in patients with local recurrence without systemic progression or isolated PSA recurrence after initial hormonal therapy when the patients show both pre-sEBRT PSA 7.0 months. (author)

  19. Will climate change promote future invasions?

    Science.gov (United States)

    Bellard, Celine; Thuiller, Wilfried; Leroy, Boris; Genovesi, Piero; Bakkenes, Michel; Courchamp, Franck

    2013-12-01

    Biological invasion is increasingly recognized as one of the greatest threats to biodiversity. Using ensemble forecasts from species distribution models to project future suitable areas of the 100 of the world's worst invasive species defined by the International Union for the Conservation of Nature, we show that both climate and land use changes will likely cause drastic species range shifts. Looking at potential spatial aggregation of invasive species, we identify three future hotspots of invasion in Europe, northeastern North America, and Oceania. We also emphasize that some regions could lose a significant number of invasive alien species, creating opportunities for ecosystem restoration. From the list of 100, scenarios of potential range distributions show a consistent shrinking for invasive amphibians and birds, while for aquatic and terrestrial invertebrates distributions are projected to substantially increase in most cases. Given the harmful impacts these invasive species currently have on ecosystems, these species will likely dramatically influence the future of biodiversity. © 2013 John Wiley & Sons Ltd.

  20. C-ERC/mesothelin provokes lymphatic invasion of colorectal adenocarcinoma.

    Science.gov (United States)

    Kawamata, Futoshi; Homma, Shigenori; Kamachi, Hirofumi; Einama, Takahiro; Kato, Yasutaka; Tsuda, Masumi; Tanaka, Shinya; Maeda, Masahiro; Kajino, Kazunori; Hino, Okio; Takahashi, Norihiko; Kamiyama, Toshiya; Nishihara, Hiroshi; Taketomi, Akinobu; Todo, Satoru

    2014-01-01

    Lymph node metastasis is a key event of colorectal cancer (CRC) progression. Mesothelin is expressed in various types of malignant tumor and associated with an unfavorable prognosis. The full-length mesothelin (Full-ERC) is cleaved by protease into membrane-bound C-ERC/mesothelin and N-ERC/mesothelin which is secreted into the blood. The aim of this study was to examine the biological role of mesothelin in CRC by clinicopathological analysis and in vitro lymphatic invasion assay. Ninety-one cases of CRC specimens were immunohistochemically examined and the localization of mesothelin in luminal membrane and/or cytoplasm was also evaluated. Lymphatic invasion assay was also performed using the human CRC cell line, WiDr, which was transfected with Full-, N- and C-ERC/mesothelin expression plasmids (Full-WiDr, N-WiDr and C-WiDr). Immunohistochemically, "luminal membrane positive" of mesothelin was identified in 37.4 %, and correlated with lymphatic permeation and lymph node metastasis, but not with patients' prognosis. Interestingly, among the patients with lymph node metastasis (N = 38), "luminal membrane positive" of mesothelin significantly correlated with unfavorable patients' outcome. In addition, lymphatic invasion assay revealed that Full-WiDr and C-WiDr more significantly invaded human lymphatic endothelial cells than the Mock-WiDr (P ERC/mesothelin associated with lymphatic invasion of cancer in vitro.

  1. Invasive amebiasis.

    Science.gov (United States)

    Grecu, F; Bulgariu, Teodora; Blanaru, Oana; Dragomir, C; Lunca, Claudia; Stratan, I; Manciuc, Carmen; Luca, V

    2006-01-01

    Digestive amoebiasis with his invasive form is an unusual pathology encountered in the temperate zone. This could lead to a life threatening complication: systemic amoebiasis. A 55-year-old male was treated successfully of systemic amoebiasis in a third referral hospital. The diagnosis was established based on epidemiology data and microscopical identification of trophozoites of Entamoeba histolytica. The amoebicidal, antibiotic and supportive treatments was firstly administrated. The clinical picture of intestinal amoebiasis raised from dysenteric syndrome to necrotizing enteritis. The bowel perforation with localized peritonitis was followed by chronic enteric fistula. Amoebic liver abscess, as the most frequent extraintestinal complication, was concomitantly diagnosed and treated. Urinary amoebiasis was considered as complication in the context of systemic dissemination: any other location could become a site of an amoebic abscess. Multidisciplinary approach was the successful key in the management of the patient, including antiparasitic therapy and antibiotic prophylaxis, intensive care and multiple surgical approaches. The diagnosis of digestive amoebiasis and systemic complication may be delayed in nonendemic areas, leading to advanced and complicated stages of the disease. The surgical approach is most efficiently to treat a large liver amoebic abscess and intraperitoneal collections.

  2. Non-invasive assessment of gastric activity

    International Nuclear Information System (INIS)

    Smallwood, R.H.; Brown, B.H.

    1983-01-01

    There have been many suggestions for the routine clinical use of the electro-enterogram, but with the exception of the reported usage in the USSR no significant penetration into medical practice has been reported elsewhere. Amongst the many suggestions have been the possible application of electrical stimulation via surface electrodes to overcome post-operative inhibition of intestinal electrical activity, which can be recorded via surface electrodes. Gastric emptying studies have shown that duodenal ulceration is associated with changes in the rate and pattern of emptying of solid meals. Identifiable patterns in the electro-gastrogram following a metal might have diagnostic application. There is some evidence of correlations of electrical activity and pathology in the large intestine. In the colon diverticular disease has been shown to change the frequency content of the slow wave electrical activity and there is some evidence that this might be recorded from surface electrodes. A major obstacle to progress remains the inability to relate non-invasive recordings to intestinal motility. The best hope may be the use of direct and yet non-invasive methods of obtaining motility and in this context real-time ultrasound imaging is probably the most promising technique. The electro-gastrogram has certainly been shown to allow recording of gastric slow wave activity and there is a reasonable hope that further methods of analysis will allow inferential information on motility to be obtained. The following section makes brief mention of these techniques

  3. Risk factors for the development of invasive cancer in unresected ductal carcinoma in situ.

    Science.gov (United States)

    Maxwell, Anthony J; Clements, Karen; Hilton, Bridget; Dodwell, David J; Evans, Andrew; Kearins, Olive; Pinder, Sarah E; Thomas, Jeremy; Wallis, Matthew G; Thompson, Alastair M

    2018-04-01

    The natural history of ductal carcinoma in situ (DCIS) remains uncertain. The risk factors for the development of invasive cancer in unresected DCIS are unclear. Women diagnosed with DCIS on needle biopsy after 1997 who did not undergo surgical resection for ≥1 year after diagnosis were identified by breast centres and the cancer registry and outcomes were reviewed. Eighty-nine women with DCIS diagnosed 1998-2010 were identified. The median age at diagnosis was 75 (range 44-94) years with median follow-up (diagnosis to death, invasive disease or last review) of 59 (12-180) months. Twenty-nine women (33%) developed invasive breast cancer after a median interval of 45 (12-144) months. 14/29 (48%) with high grade, 10/31 (32%) with intermediate grade and 3/17 (18%) with low grade DCIS developed invasive cancer after median intervals of 38, 60 and 51 months. The cumulative incidence of invasion was significantly higher in high grade DCIS than other grades (p = .0016, log-rank test). Invasion was more frequent in lesions with calcification as the predominant feature (23/50 v. 5/25; p = .042) and in younger women (p = .0002). Endocrine therapy was associated with a lower rate of invasive breast cancer (p = .048). High cytonuclear grade, mammographic microcalcification, young age and lack of endocrine therapy were risk factors for DCIS progression to invasive cancer. Surgical excision of high grade DCIS remains the treatment of choice. Given the uncertain long-term natural history of non-high grade DCIS, the option of active surveillance of women with this condition should be offered within a clinical trial. Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.

  4. Resveratrol Inhibits the Invasion of Glioblastoma-Initiating Cells via Down-Regulation of the PI3K/Akt/NF-κB Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Yuming Jiao

    2015-06-01

    Full Text Available Invasion and metastasis of glioblastoma-initiating cells (GICs are thought to be responsible for the progression and recurrence of glioblastoma multiforme (GBM. A safe drug that can be applied during the rest period of temozolomide (TMZ maintenance cycles would greatly improve the prognosis of GBM patients by inhibiting GIC invasion. Resveratrol (RES is a natural compound that exhibits anti-invasion properties in multiple tumor cell lines. The current study aimed to evaluate whether RES can inhibit GIC invasion in vitro and in vivo. GICs were identified using CD133 and Nestin immunofluorescence staining and tumorigenesis in non-obese diabetic severe combined immunodeficient (NOD/SCID mice. Invasive behaviors, including the adhesion, invasion and migration of GICs, were determined by tumor invasive assays in vitro and in vivo. The activity of matrix metalloproteinases (MMPs was measured by the gelatin zymography assay. Western blotting analysis and immunofluorescence staining were used to determine the expression of signaling effectors in GICs. We demonstrated that RES suppressed the adhesion, invasion and migration of GICs in vitro and in vivo. Moreover, we proved that RES inhibited the invasion of GICs via the inhibition of PI3K/Akt/NF-κB signal transduction and the subsequent suppression of MMP-2 expression.

  5. Citizen Science and Open Data: a Model for Invasive Alien Plant Species in Kenya's Northern Rangelands

    Science.gov (United States)

    Amirazodi, S.; Griffin, R.; Flores Cordova, A. I.; Ouko, E.; Omondi, S.; Mugo, R. M.; Farah, H.; Flores Cordova, A. I.; Adams, E. C.

    2017-12-01

    Invasive species in African savannas pose great threat to the native biodiversity and changes ecosystem functioning. In the forest sector, for instance Acacia species are important sources of fuel-wood, yet at the same time they have increased strain on water resources and shrunken forage spaces for both livestock and wildlife. In recently infested regions, invasive species can progress through the stages of introduction, establishment and dispersal to a full range. Currently there is much worldwide interest in predicting distributions of invasive species, and several organizations are faced with questions of whether and how to tackle such environmental challenges, or how to interpret predictions from the science community. Conservation practioners require mapped estimates of where species could persist in a given region, and this is associated to information about the biotope - i.e. the geographic location of the species' niche. The process of collecting species distribution data for identifying the potential distribution of the invasive species in the invaded ranges has become a challenge both in terms of resource and time allocation. This study highlights innovative approaches in crowdsourcing validation data in mapping and modelling invasive species (Acacia reficiens and Cactus) through involvement of the local communities. The general approach was to model the distribution of A. reficiens and Cactus (Opuntia Spp) using occurrence records from native range, then project the model into new regions to assess susceptibility to invasion using climatic and topographic environmental variables. The models performed better than random prediction (P 0.75.

  6. A human breast cell model of pre-invasive to invasive transition

    Energy Technology Data Exchange (ETDEWEB)

    Bissell, Mina J; Rizki, Aylin; Weaver, Valerie M.; Lee, Sun-Young; Rozenberg, Gabriela I.; Chin, Koei; Myers, Connie A.; Bascom, Jamie L.; Mott, Joni D.; Semeiks, Jeremy R.; Grate, Leslie R.; Mian, I. Saira; Borowsky, Alexander D.; Jensen, Roy A.; Idowu, Michael O.; Chen, Fanqing; Chen, David J.; Petersen, Ole W.; Gray, Joe W.; Bissell, Mina J.

    2008-03-10

    A crucial step in human breast cancer progression is the acquisition of invasiveness. There is a distinct lack of human cell culture models to study the transition from pre-invasive to invasive phenotype as it may occur 'spontaneously' in vivo. To delineate molecular alterations important for this transition, we isolated human breast epithelial cell lines that showed partial loss of tissue polarity in three-dimensional reconstituted-basement membrane cultures. These cells remained non-invasive; however, unlike their non-malignant counterparts, they exhibited a high propensity to acquire invasiveness through basement membrane in culture. The genomic aberrations and gene expression profiles of the cells in this model showed a high degree of similarity to primary breast tumor profiles. The xenograft tumors formed by the cell lines in three different microenvironments in nude mice displayed metaplastic phenotypes, including squamous and basal characteristics, with invasive cells exhibiting features of higher grade tumors. To find functionally significant changes in transition from pre-invasive to invasive phenotype, we performed attribute profile clustering analysis on the list of genes differentially expressed between pre-invasive and invasive cells. We found integral membrane proteins, transcription factors, kinases, transport molecules, and chemokines to be highly represented. In addition, expression of matrix metalloproteinases MMP-9,-13,-15,-17 was up regulated in the invasive cells. Using siRNA based approaches, we found these MMPs to be required for the invasive phenotype. This model provides a new tool for dissection of mechanisms by which pre-invasive breast cells could acquire invasiveness in a metaplastic context.

  7. Interactions between CXCR4 and CXCL12 promote cell migration and invasion of canine hemangiosarcoma.

    Science.gov (United States)

    Im, K S; Graef, A J; Breen, M; Lindblad-Toh, K; Modiano, J F; Kim, J-H

    2017-06-01

    The CXCR4/CXCL12 axis plays an important role in cell locomotion and metastasis in many cancers. In this study, we hypothesized that the CXCR4/CXCL12 axis promotes migration and invasion of canine hemangiosarcoma (HSA) cells. Transcriptomic analysis across 12 HSA cell lines and 58 HSA whole tumour tissues identified heterogeneous expression of CXCR4 and CXCL12, which was associated with cell movement. In vitro, CXCL12 promoted calcium mobilization, cell migration and invasion that were directly proportional to surface expression of CXCR4; furthermore, these responses proved sensitive to the CXCR4 antagonist, AMD3100, in HSA cell lines. These results indicate that CXCL12 potentiates migration and invasion of canine HSA cells through CXCR4 signalling. The direct relationship between these responses in HSA cells suggests that the CXCR4/CXCL12 axis contributes to HSA progression. © 2015 John Wiley & Sons Ltd.

  8. Principles for ecologically based invasive plant management

    Science.gov (United States)

    Jeremy J. James; Brenda S. Smith; Edward A. Vasquez; Roger L. Sheley

    2010-01-01

    Land managers have long identified a critical need for a practical and effective framework for designing restoration strategies, especially where invasive plants dominate. A holistic, ecologically based, invasive plant management (EBIPM) framework that integrates ecosystem health assessment, knowledge of ecological processes, and adaptive management into a successional...

  9. Secretome signature of invasive glioblastoma multiforme.

    Science.gov (United States)

    Formolo, Catherine A; Williams, Russell; Gordish-Dressman, Heather; MacDonald, Tobey J; Lee, Norman H; Hathout, Yetrib

    2011-07-01

    The incurability of malignant glioblastomas is mainly attributed to their highly invasive nature coupled with resistance to chemo- and radiation therapy. Because invasiveness is partially dictated by the proteins these tumors secrete we used SILAC to characterize the secretomes of four glioblastoma cell lines (LN18, T98, U118 and U87). Although U87 and U118 cells both secreted high levels of well-known invasion promoting proteins, a Matrigel invasion assay showed U87 cells to be eight times more invasive than U118 cells, suggesting that additional proteins secreted by U87 cells may contribute to the highly invasive phenotype. Indeed, we identified a number of proteins highly or exclusively expressed by U87 cells as compared to the less invasive cell lines. The most striking of these include ADAM9, ADAM10, cathepsin B, cathepsin L1, osteopontin, neuropilin-1, semaphorin-7A, suprabasin, and chitinase-3-like protein 1. U87 cells also expressed significantly low levels of some cell adhesion proteins such as periostin and EMILIN-1. Correlation of secretome profiles with relative levels of invasiveness using Pavlidis template matching further indicated potential roles for these proteins in U87 glioblastoma invasion. Antibody inhibition of CH3L1 reduced U87 cell invasiveness by 30%.

  10. Down-regulation of S100C is associated with bladder cancer progression and poor survival

    DEFF Research Database (Denmark)

    Memon, Ashfaque Ahmed; Sorensen, Boe Sandahl; Meldgaard, Peter

    2005-01-01

    cancer biopsy samples obtained from 88 patients followed for a median of 23 months (range, 1-97 months). RESULTS: We found a significantly lower mRNA expression of S100C in connective tissue invasive tumors (T1, P = 0.0030) and muscle invasive tumors [(T2-T4), P ...PURPOSE: The goal of this study was to identify proteins down-regulated during bladder cancer progression. EXPERIMENTAL DESIGN: By using comparative proteome analysis and measurement of mRNA, we found a significant down-regulation of S100C, a member of the S100 family of proteins, in T24 (grade 3...

  11. Amplification of specific chromosomal regions assessed by fluorescent in situ hybridization on Pap smears to be added as screening tool for identifying women at risk of progressing to cervical cancer.

    Science.gov (United States)

    Upendram, Pavani; Sahni, Shubhi; Mohiuddin, Khaliq; Poornima, Subhadra; Gourishankar, Bhanumathy; Kumar Vattam, Kiran; Boddala, Pavani; Jayashankar, E; Mohiuddin, Shakera; Kamineni, Vasundhara; Mohan, Vasavi; Houldsworth, Jane; Hasan, Qurratulain

    2017-10-01

    Cervical carcinoma is a frequent malignancy in developing countries despite being a preventable disease. For the first time, four screening tests were used simultaneously for identifying women with a risk of developing cervical cancer, to help clinicians and policy makers to implement the best strategy for reducing the burden of this disease. Women visiting a hospital in India were enrolled after institutional ethics clearance and informed consent. Visual inspection using acetic acid and Pap smear tests were performed on 2683 women, and 104 had abnormal cytology: atypical squamous cells of undetermined significance (n = 29), low-grade squamous intraepithelial lesion (n = 41), high-grade squamous intraepithelial lesion (n = 17), and squamous cell carcinoma (n = 17). These and 96 samples, with normal cytology, were subjected to high-risk human papilloma virus testing and fluorescent in situ hybridization evaluation. Women with abnormal cytology were followed for 5 years and evaluated with colposcopy-guided biopsy. Three accepted methods of screening and one novel fluorescent in situ hybridization assay were carried out in 200 cases. Cutoffs for fluorescent in situ hybridization were established. The screening methods had 88%-96% negative predictive value, while positive predictive value was low (20%) for visual inspection using acetic acid, 47% for fluorescent in situ hybridization, 56% for high-risk human papilloma virus, and 73% for combined high-risk human papilloma virus and fluorescent in situ hybridization. Combined high-risk human papilloma virus and fluorescent in situ hybridization had 94% sensitivity, specificity, and negative predictive value, suggesting that simultaneous screening with these two tests is appropriate for identifying women progressing to cervical cancer and not visual inspection using acetic acid, which has low positive predictive value and Pap cytology which requires to be repeated. Policy makers and clinicians can assess

  12. Smartphone-assisted minimally invasive neurosurgery.

    Science.gov (United States)

    Mandel, Mauricio; Petito, Carlo Emanuel; Tutihashi, Rafael; Paiva, Wellingson; Abramovicz Mandel, Suzana; Gomes Pinto, Fernando Campos; Ferreira de Andrade, Almir; Teixeira, Manoel Jacobsen; Figueiredo, Eberval Gadelha

    2018-03-13

    OBJECTIVE Advances in video and fiber optics since the 1990s have led to the development of several commercially available high-definition neuroendoscopes. This technological improvement, however, has been surpassed by the smartphone revolution. With the increasing integration of smartphone technology into medical care, the introduction of these high-quality computerized communication devices with built-in digital cameras offers new possibilities in neuroendoscopy. The aim of this study was to investigate the usefulness of smartphone-endoscope integration in performing different types of minimally invasive neurosurgery. METHODS The authors present a new surgical tool that integrates a smartphone with an endoscope by use of a specially designed adapter, thus eliminating the need for the video system customarily used for endoscopy. The authors used this novel combined system to perform minimally invasive surgery on patients with various neuropathological disorders, including cavernomas, cerebral aneurysms, hydrocephalus, subdural hematomas, contusional hematomas, and spontaneous intracerebral hematomas. RESULTS The new endoscopic system featuring smartphone-endoscope integration was used by the authors in the minimally invasive surgical treatment of 42 patients. All procedures were successfully performed, and no complications related to the use of the new method were observed. The quality of the images obtained with the smartphone was high enough to provide adequate information to the neurosurgeons, as smartphone cameras can record images in high definition or 4K resolution. Moreover, because the smartphone screen moves along with the endoscope, surgical mobility was enhanced with the use of this method, facilitating more intuitive use. In fact, this increased mobility was identified as the greatest benefit of the use of the smartphone-endoscope system compared with the use of the neuroendoscope with the standard video set. CONCLUSIONS Minimally invasive approaches

  13. Identification of genes regulating migration and invasion using a new model of metastatic prostate cancer

    International Nuclear Information System (INIS)

    Banyard, Jacqueline; Chung, Ivy; Migliozzi, Matthew; Phan, Derek T; Wilson, Arianne M; Zetter, Bruce R; Bielenberg, Diane R

    2014-01-01

    Understanding the complex, multistep process of metastasis remains a major challenge in cancer research. Metastasis models can reveal insights in tumor development and progression and provide tools to test new intervention strategies. To develop a new cancer metastasis model, we used DU145 human prostate cancer cells and performed repeated rounds of orthotopic prostate injection and selection of subsequent lymph node metastases. Tumor growth, metastasis, cell migration and invasion were analyzed. Microarray analysis was used to identify cell migration- and cancer-related genes correlating with metastasis. Selected genes were silenced using siRNA, and their roles in cell migration and invasion were determined in transwell migration and Matrigel invasion assays. Our in vivo cycling strategy created cell lines with dramatically increased tumorigenesis and increased ability to colonize lymph nodes (DU145LN1-LN4). Prostate tumor xenografts displayed increased vascularization, enlarged podoplanin-positive lymphatic vessels and invasive margins. Microarray analysis revealed gene expression profiles that correlated with metastatic potential. Using gene network analysis we selected 3 significantly upregulated cell movement and cancer related genes for further analysis: EPCAM (epithelial cell adhesion molecule), ITGB4 (integrin β4) and PLAU (urokinase-type plasminogen activator (uPA)). These genes all showed increased protein expression in the more metastatic DU145-LN4 cells compared to the parental DU145. SiRNA knockdown of EpCAM, integrin-β4 or uPA all significantly reduced cell migration in DU145-LN4 cells. In contrast, only uPA siRNA inhibited cell invasion into Matrigel. This role of uPA in cell invasion was confirmed using the uPA inhibitors, amiloride and UK122. Our approach has identified genes required for the migration and invasion of metastatic tumor cells, and we propose that our new in vivo model system will be a powerful tool to interrogate the metastatic

  14. Minimally invasive surgical therapies for benign prostatic hypertrophy: The rise in minimally invasive surgical therapies

    OpenAIRE

    Christidis, Daniel; McGrath, Shannon; Perera, Marlon; Manning, Todd; Bolton, Damien; Lawrentschuk, Nathan

    2017-01-01

    The prevalence of benign prostatic hypertrophy (BPH) causing bothersome lower urinary tract symptoms increases with our ageing population. Treatment of BPH traditionally begins with medical therapy and surgical intervention is then considered for those whose symptoms progress despite treatment. Minimally invasive surgical therapies have been developed as an intermediary in the treatment of BPH with the aim of decreasing the invasiveness of interventions. These therapies also aim to reduce mor...

  15. National invasive species program

    Science.gov (United States)

    Anna Rinick

    2007-01-01

    The structure and function of the National Invasive Species Council was presented below. The names and contact information for the USDA Invasive Species coordinators as of February 2006 were presented on the next page.

  16. Cancer invasion and the microenvironment: plasticity and reciprocity.

    NARCIS (Netherlands)

    Friedl, P.H.A.; Alexander, S.

    2011-01-01

    Cancer invasion is a cell- and tissue-driven process for which the physical, cellular, and molecular determinants adapt and react throughout the progression of the disease. Cancer invasion is initiated and maintained by signaling pathways that control cytoskeletal dynamics in tumor cells and the

  17. The assessment of invasive alien plant species removal programs ...

    African Journals Online (AJOL)

    Yusuf Adam

    Abstract. The occupation of natural environments by invasive alien plant species (IAPs) are a growing threat to ecosystems. This has resulted in the creation of government-based initiatives to mitigate invasion, however, there has been little progress towards assessing these initiatives. Remote sensing is a commonly used ...

  18. The assessment of invasive alien plant species removal programs ...

    African Journals Online (AJOL)

    The occupation of natural environments by invasive alien plant species (IAPs) are a growing threat to ecosystems. This has resulted in the creation of government-based initiatives to mitigate invasion, however, there has been little progress towards assessing these initiatives. Remote sensing is a commonly used tool in the ...

  19. Non-muscle-invasive bladder cancer

    DEFF Research Database (Denmark)

    Malmström, Per-Uno; Agrawal, Sachin; Bläckberg, Mats

    2017-01-01

    The management of non-muscle-invasive bladder cancer (NMIBC) has evolved from the first reports on bladder endoscopy and transurethral resection to the introduction of adjuvant intravesical treatment. However, disease recurrence and progression remain an ongoing risk, placing a heavy burden on he...

  20. Invasive plants have broader physiological niches.

    Science.gov (United States)

    Higgins, Steven I; Richardson, David M

    2014-07-22

    Invasive species cost the global economy billions of dollars each year, but ecologists have struggled to predict the risk of an introduced species naturalizing and invading. Although carefully designed experiments are needed to fully elucidate what makes some species invasive, much can be learned from unintentional experiments involving the introduction of species beyond their native ranges. Here, we assess invasion risk by linking a physiologically based species distribution model with data on the invasive success of 749 Australian acacia and eucalypt tree species that have, over more than a century, been introduced around the world. The model correctly predicts 92% of occurrences observed outside of Australia from an independent dataset. We found that invasiveness is positively associated with the projection of physiological niche volume in geographic space, thereby illustrating that species tolerant of a broader range of environmental conditions are more likely to be invasive. Species achieve this broader tolerance in different ways, meaning that the traits that define invasive success are context-specific. Hence, our study reconciles studies that have failed to identify the traits that define invasive success with the urgent and pragmatic need to predict invasive success.

  1. Klebsiella pneumoniae Invasive Syndrome

    Directory of Open Access Journals (Sweden)

    Vasco Evangelista

    2018-01-01

    Full Text Available Klebsiella pneumoniae invasive syndrome (KPIS is a rare clinical condition characterized by primary liver abscess associated with metastatic infection. Most case reports are from Southeast Asia, with only one case described in Portugal. The Authors present the case of a 44-year-old man with a history of fever, dry cough and cervicalgia. A thoracic computed tomography (CT scan showed multiple pulmonary and hepatic nodules, suggestive of metastatic malignancy. Both blood cultures and bronchoalveolar lavage were positive for Klebsiella pneumoniae. Imaging studies were repeated during his hospital stay, showing a reduction in both number and volume of identified lesions, thus revealing their infectious nature. This case illustrates how much this entity can mimic other illnesses.

  2. Rab25 augments cancer cell invasiveness through a β1 integrin/EGFR/VEGF-A/Snail signaling axis and expression of fascin.

    Science.gov (United States)

    Jeong, Bo Young; Cho, Kyung Hwa; Jeong, Kang Jin; Park, Yun-Yong; Kim, Jin Man; Rha, Sun Young; Park, Chang Gyo; Mills, Gordon B; Cheong, Jae-Ho; Lee, Hoi Young

    2018-01-26

    The small GTP-binding protein Rab25 is associated with tumor formation and progression. However, recent studies have shown discordant effects of Rab25 on cancer cell progression depending on cell lineage. In the present study, we elucidate the underlying mechanisms by which Rab25 induces cellular invasion. We demonstrate that Rab25 increases β1 integrin levels and subsequent activation of EGFR and upregulation of VEGF-A expression, leading to increased Snail expression, epithelial-to-mesenchymal transition and cancer cell invasiveness. Strikingly, we identify that Snail mediates Rab25-induced cancer cell invasiveness through fascin expression and that ectopic expression of Rab25 aggravates metastasis of ovarian cancer cells to the lung. We thus demonstrate a novel role of a β1 integrin/EGFR/VEGF-A/Snail signaling cascade in Rab25-induced cancer cell aggressiveness through induction of fascin expression, thus providing novel biomarkers and potential therapeutic targets for Rab25-expressing cancer cells.

  3. Chapter 8: Invasive fungal rhinosinusitis.

    Science.gov (United States)

    Duggal, Praveen; Wise, Sarah K

    2013-01-01

    Invasive fungal rhinosinusitis (IFRS) is a disease of the paranasal sinuses and nasal cavity that typically affects immunocompromised patients in the acute fulminant form. Early symptoms can often mimic rhinosinusitis, while late symptoms can cause significant morbidity and mortality. Swelling and mucosal thickening can quickly progress to pale or necrotic tissue in the nasal cavity and sinuses, and the disease can rapidly spread and invade the palate, orbit, cavernous sinus, cranial nerves, skull base, carotid artery, and brain. IFRS can be life threatening if left undiagnosed or untreated. While the acute fulminant form of IFRS is the most rapidly progressive and destructive, granulomatous and chronic forms also exist. Diagnosis of IFRS often mandates imaging studies in conjunction with clinical, endoscopic, and histopathological examination. Treatment of IFRS consists of reversing the underlying immunosuppression, antifungal therapy, and aggressive surgical debridement. With early diagnosis and treatment, IFRS can be treated and increase patient survival.

  4. Chapter 8: Invasive fungal rhinosinusitis.

    Science.gov (United States)

    Duggal, Praveen; Wise, Sarah K

    2013-05-01

    Invasive fungal rhinosinusitis (IFRS) is a disease of the paranasal sinuses and nasal cavity that typically affects immunocompromised patients in the acute fulminant form. Early symptoms can often mimic rhinosinusitis, while late symptoms can cause significant morbidity and mortality. Swelling and mucosal thickening can quickly progress to pale or necrotic tissue in the nasal cavity and sinuses, and the disease can rapidly spread and invade the palate, orbit, cavernous sinus, cranial nerves, skull base, carotid artery, and brain. IFRS can be life threatening if left undiagnosed or untreated. While the acute fulminant form of IFRS is the most rapidly progressive and destructive, granulomatous and chronic forms also exist. Diagnosis of IFRS often mandates imaging studies in conjunction with clinical, endoscopic, and histopathological examination. Treatment of IFRS consists of reversing the underlying immunosuppression, antifungal therapy, and aggressive surgical debridement. With early diagnosis and treatment, IFRS can be treated and increase patient survival.

  5. Comparative proteomic analysis of ductal and lobular invasive breast carcinoma.

    Science.gov (United States)

    Oliveira, N C S; Gomig, T H B; Milioli, H H; Cordeiro, F; Costa, G G; Urban, C A; Lima, R S; Cavalli, I J; Ribeiro, E M S F

    2016-04-04

    Breast cancer is the second most common cancer worldwide and the first among women. Invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) are the two major histological subtypes, and the clinical and molecular differences between them justify the search for new markers to distinguish them. As proteomic analysis allows for a powerful and analytical approach to identify potential biomarkers, we performed a comparative analysis of IDC and ILC samples by using two-dimensional electrophoresis and mass spectrometry. Twenty-three spots were identified corresponding to 10 proteins differentially expressed between the two subtypes. ACTB, ACTG, TPM3, TBA1A, TBA1B, VIME, TPIS, PDIA3, PDIA6, and VTDB were upregulated in ductal carcinoma compared to in lobular carcinoma samples. Overall, these 10 proteins have a key role in oncogenesis. Their specific functions and relevance in cancer initiation and progression are further discussed in this study. The identified peptides represent promising biomarkers for the differentiation of ductal and lobular breast cancer subtypes, and for future interventions based on tailored therapy.

  6. E-commerce trade in invasive plants.

    Science.gov (United States)

    Humair, Franziska; Humair, Luc; Kuhn, Fabian; Kueffer, Christoph

    2015-12-01

    Biological invasions are a major concern in conservation, especially because global transport of species is still increasing rapidly. Conservationists hope to anticipate and thus prevent future invasions by identifying and regulating potentially invasive species through species risk assessments and international trade regulations. Among many introduction pathways of non-native species, horticulture is a particularly important driver of plant invasions. In recent decades, the horticultural industry expanded globally and changed structurally through the emergence of new distribution channels, including internet trade (e-commerce). Using an automated search algorithm, we surveyed, on a daily basis, e-commerce trade on 10 major online auction sites (including eBay) of approximately three-fifths of the world's spermatophyte flora. Many recognized invasive plant species (>500 species) (i.e., species associated with ecological or socio-economic problems) were traded daily worldwide on the internet. A markedly higher proportion of invasive than non-invasive species were available online. Typically, for a particular plant family, 30-80% of recognized invasive species were detected on an auction site, but only a few percentages of all species in the plant family were detected on a site. Families that were more traded had a higher proportion of invasive species than families that were less traded. For woody species, there was a significant positive relationship between the number of regions where a species was sold and the number of regions where it was invasive. Our results indicate that biosecurity is not effectively regulating online plant trade. In the future, automated monitoring of e-commerce may help prevent the spread of invasive species, provide information on emerging trade connectivity across national borders, and be used in horizon scanning exercises for early detection of new species and their geographic source areas in international trade. © 2015 Society for

  7. A cell-based high-content screening assay reveals activators and inhibitors of cancer cell invasion.

    Science.gov (United States)

    Quintavalle, Manuela; Elia, Leonardo; Price, Jeffrey H; Heynen-Genel, Susanne; Courtneidge, Sara A

    2011-07-26

    Acquisition of invasive cell behavior underlies tumor progression and metastasis. To further define the molecular mechanisms underlying invasive behavior, we developed a high-throughput screening strategy to quantitate invadopodia, which are actin-rich membrane protrusions of cancer cells that contribute to tissue invasion and matrix remodeling. We tested the LOPAC 1280 collection of pharmacologically active agents in a high-content, image-based assay and identified compounds that inhibited invadopodium formation without overt toxicity, as well as compounds that increased invadopodia number. The chemotherapeutic agent paclitaxel increased both the number of invadopodia and the invasive behavior of various human cancer cell lines, effects that have potential clinical implications for its use before surgical removal of a primary tumor (neoadjuvant therapy) or in patients with chemoresistant tumors. Several compounds that inhibited invasion have been characterized as cyclin-dependent kinase (Cdk) inhibitors, and loss-of-function experiments determined that Cdk5 was the relevant target. We further determined that Cdk5 promoted both invadopodium formation and cancer cell invasion by phosphorylating and thus decreasing the abundance of the actin regulatory protein caldesmon.

  8. Role of IGF-1/IGF-1R in regulation of invasion in DU145 prostate cancer cells

    Directory of Open Access Journals (Sweden)

    Setya Hemani

    2008-07-01

    Full Text Available Abstract Background Prostate cancer progression to androgen independence is the primary cause of mortality by this tumor type. The IGF-1/IGF-1R axis is well known to contribute to prostate cancer initiation, but its contribution to invasiveness and the downstream signalling mechanisms that are involved are unclear at present. Results We examined the invasive response of androgen independent DU145 prostate carcinoma cells to IGF-1 stimulation using Matrigel assays. We then examined the signaling mechanisms and protease activities that are associated with this response. IGF-1 significantly increased the invasive capacity of DU145 cells in vitro, and this increase was inhibited by blocking IGF-1R. We further demonstrated that specific inhibitors of the MAPK and PI3-K pathways decrease IGF-1-mediated invasion. To determine potential molecular mechanisms for this change in invasive capacity, we examined changes in expression and activity of matrix metalloproteinases. We observed that IGF-1 increases the enzymatic activity of MMP-2 and MMP-9 in DU145 cells. These changes in activity are due to differences in expression in the case of MMP-9 but not in the case of MMP-2. This observation is corroborated by the fact that correlated changes of expression in a regulator of MMP-2, TIMP-2, were also seen. Conclusion This work identifies a specific effect of IGF-1 on the invasive capacity of DU145 prostate cancer cells, and furthermore delineates mechanisms that contribute to this effect.

  9. Progress Report

    DEFF Research Database (Denmark)

    Duer, Karsten

    1999-01-01

    Progress report describing the work carried out by the Danish participant in the ALTSET project in the period January 1999 to July 1999.......Progress report describing the work carried out by the Danish participant in the ALTSET project in the period January 1999 to July 1999....

  10. Invasive Species Biology, Control, and Research. Part 1: Kudzu (Pueraria montana)

    National Research Council Canada - National Science Library

    Guertin, Patrick J; Denight, Michael L; Gebhart, Dick L; Nelson, Linda

    2008-01-01

    ..., and damage to equipment and structures. Of the 11 plant species (or groups) identified by installations as uncontrolled vegetation, six were invasive plants, of which the two invasive plants most commonly identified were Kudzu (Pueraria montana...

  11. Invasive Species Biology, Control, and Research. Part 2. Multiflora Rose (Rosa multiflora)

    National Research Council Canada - National Science Library

    Denight, Michael L; Guertin, Patrick J; Gebhart, Dick L; Nelson, Linda

    2008-01-01

    ..., and damage to equipment and structures. Of the 11 plant species (or groups) identified by installations as "uncontrolled vegetation," six were invasive plants, of which the two invasive plants most commonly identified were Kudzu (Pueraria montana...

  12. Nm23/nucleoside diphosphate kinase-A as a potent prognostic marker in invasive pancreatic ductal carcinoma identified by proteomic analysis of laser micro-dissected formalin-fixed paraffin-embedded tissue

    Directory of Open Access Journals (Sweden)

    Takadate Tatsuyuki

    2012-06-01

    Full Text Available Abstract Background Pancreatic cancer is among the most lethal malignancies worldwide. This study aimed to identify a novel prognostic biomarker, facilitating treatment selection, using mass spectrometry (MS-based proteomic analysis with formalin-fixed paraffin-embedded (FFPE tissue. Results The two groups with poor prognosis (n = 4 and with better prognosis (n = 4 had been carefully chosen among 96 resected cases of pancreatic cancer during 1998 to 2007 in Tohoku University Hospital. Although those 2 groups had adjusted background (UICC-Stage IIB, Grade2, R0, gemcitabine adjuvant, there was a significant difference in postoperative mean survival time (poor 21.0 months, better 58.1 months, P = 0.0067. Cancerous epithelial cells collected from FFPE tissue sections by laser micro-dissection (LMD were processed for liquid chromatography-tandem mass spectrometry (LC-MS/MS. In total, 1099 unique proteins were identified and 6 proteins showed different expressions in the 2 groups by semi-quantitative comparison. Among these 6 proteins, we focused on Nm23/Nucleoside Diphosphate Kinase A (NDPK-A and immunohistochemically confirmed its expression in the cohort of 96 cases. Kaplan-Meier analysis showed high Nm23/NDPK-A expression to correlate with significantly worse overall survival (P = 0.0103. Moreover, in the multivariate Cox regression model, Nm23/NDPK-A over-expression remained an independent predictor of poor survival with a hazard ratio of 1.97 (95% CI 1.16-3.56, P = 0.0110. Conclusions We identified 6 candidate prognostic markers for postoperative pancreatic cancer using FFPE tissues and immunohistochemically demonstrated high Nm23/NDPK-A expression to be a useful prognostic marker for pancreatic cancer.

  13. Optimization of Invasion-Specific Effects of Betulin Derivatives on Prostate Cancer Cells through Lead Development.

    Directory of Open Access Journals (Sweden)

    Ville Härmä

    Full Text Available The anti-invasive and anti-proliferative effects of betulins and abietane derivatives was systematically tested using an organotypic model system of advanced, castration-resistant prostate cancers. A preliminary screen of the initial set of 93 compounds was performed in two-dimensional (2D growth conditions using non-transformed prostate epithelial cells (EP156T, an androgen-sensitive prostate cancer cell line (LNCaP, and the castration-resistant, highly invasive cell line PC-3. The 25 most promising compounds were all betulin derivatives. These were selected for a focused secondary screen in three-dimensional (3D growth conditions, with the goal to identify the most effective and specific anti-invasive compounds. Additional sensitivity and cytotoxicity tests were then performed using an extended cell line panel. The effects of these compounds on cell cycle progression, mitosis, proliferation and unspecific cytotoxicity, versus their ability to specifically interfere with cell motility and tumor cell invasion was addressed. To identify potential mechanisms of action and likely compound targets, multiplex profiling of compound effects on a panel of 43 human protein kinases was performed. These target de-convolution studies, combined with the phenotypic analyses of multicellular organoids in 3D models, revealed specific inhibition of AKT signaling linked to effects on the organization of the actin cytoskeleton as the most likely driver of altered cell morphology and motility.

  14. Optimization of Invasion-Specific Effects of Betulin Derivatives on Prostate Cancer Cells through Lead Development.

    Science.gov (United States)

    Härmä, Ville; Haavikko, Raisa; Virtanen, Johannes; Ahonen, Ilmari; Schukov, Hannu-Pekka; Alakurtti, Sami; Purev, Enkhee; Rischer, Heiko; Yli-Kauhaluoma, Jari; Moreira, Vânia M; Nees, Matthias; Oksman-Caldentey, Kirsi-Marja

    2015-01-01

    The anti-invasive and anti-proliferative effects of betulins and abietane derivatives was systematically tested using an organotypic model system of advanced, castration-resistant prostate cancers. A preliminary screen of the initial set of 93 compounds was performed in two-dimensional (2D) growth conditions using non-transformed prostate epithelial cells (EP156T), an androgen-sensitive prostate cancer cell line (LNCaP), and the castration-resistant, highly invasive cell line PC-3. The 25 most promising compounds were all betulin derivatives. These were selected for a focused secondary screen in three-dimensional (3D) growth conditions, with the goal to identify the most effective and specific anti-invasive compounds. Additional sensitivity and cytotoxicity tests were then performed using an extended cell line panel. The effects of these compounds on cell cycle progression, mitosis, proliferation and unspecific cytotoxicity, versus their ability to specifically interfere with cell motility and tumor cell invasion was addressed. To identify potential mechanisms of action and likely compound targets, multiplex profiling of compound effects on a panel of 43 human protein kinases was performed. These target de-convolution studies, combined with the phenotypic analyses of multicellular organoids in 3D models, revealed specific inhibition of AKT signaling linked to effects on the organization of the actin cytoskeleton as the most likely driver of altered cell morphology and motility.

  15. Molecular Signature for Lymphatic Invasion Associated with Survival of Epithelial Ovarian Cancer.

    Science.gov (United States)

    Paik, E Sun; Choi, Hyun Jin; Kim, Tae-Joong; Lee, Jeong-Won; Kim, Byoung-Gie; Bae, Duk-Soo; Choi, Chel Hun

    2018-04-01

    We aimed to develop molecular classifier that can predict lymphatic invasion and their clinical significance in epithelial ovarian cancer (EOC) patients. We analyzed gene expression (mRNA, methylated DNA) in data from The Cancer Genome Atlas. To identify molecular signatures for lymphatic invasion, we found differentially expressed genes. The performance of classifier was validated by receiver operating characteristics analysis, logistic regression, linear discriminant analysis (LDA), and support vector machine (SVM). We assessed prognostic role of classifier using random survival forest (RSF) model and pathway deregulation score (PDS). For external validation,we analyzed microarray data from 26 EOC samples of Samsung Medical Center and curatedOvarianData database. We identified 21 mRNAs, and seven methylated DNAs from primary EOC tissues that predicted lymphatic invasion and created prognostic models. The classifier predicted lymphatic invasion well, which was validated by logistic regression, LDA, and SVM algorithm (C-index of 0.90, 0.71, and 0.74 for mRNA and C-index of 0.64, 0.68, and 0.69 for DNA methylation). Using RSF model, incorporating molecular data with clinical variables improved prediction of progression-free survival compared with using only clinical variables (p < 0.001 and p=0.008). Similarly, PDS enabled us to classify patients into high-risk and low-risk group, which resulted in survival difference in mRNA profiles (log-rank p-value=0.011). In external validation, gene signature was well correlated with prediction of lymphatic invasion and patients' survival. Molecular signature model predicting lymphatic invasion was well performed and also associated with survival of EOC patients.

  16. Somatic LKB1 mutations promote cervical cancer progression.

    Directory of Open Access Journals (Sweden)

    Shana N Wingo

    Full Text Available Human Papilloma Virus (HPV is the etiologic agent for cervical cancer. Yet, infection with HPV is not sufficient to cause cervical cancer, because most infected women develop transient epithelial dysplasias that spontaneously regress. Progression to invasive cancer has been attributed to diverse host factors such as immune or hormonal status, as no recurrent genetic alterations have been identified in cervical cancers. Thus, the pressing question as to the biological basis of cervical cancer progression has remained unresolved, hampering the development of novel therapies and prognostic tests. Here we show that at least 20% of cervical cancers harbor somatically-acquired mutations in the LKB1 tumor suppressor. Approximately one-half of tumors with mutations harbored single nucleotide substitutions or microdeletions identifiable by exon sequencing, while the other half harbored larger monoallelic or biallelic deletions detectable by multiplex ligation probe amplification (MLPA. Biallelic mutations were identified in most cervical cancer cell lines; HeLa, the first human cell line, harbors a homozygous 25 kb deletion that occurred in vivo. LKB1 inactivation in primary tumors was associated with accelerated disease progression. Median survival was only 13 months for patients with LKB1-deficient tumors, but >100 months for patients with LKB1-wild type tumors (P = 0.015, log rank test; hazard ratio = 0.25, 95% CI = 0.083 to 0.77. LKB1 is thus a major cervical tumor suppressor, demonstrating that acquired genetic alterations drive progression of HPV-induced dysplasias to invasive, lethal cancers. Furthermore, LKB1 status can be exploited clinically to predict disease recurrence.

  17. Prognostic Performance and Reproducibility of the 1973 and 2004/2016 World Health Organization Grading Classification Systems in Non-muscle-invasive Bladder Cancer: A European Association of Urology Non-muscle Invasive Bladder Cancer Guidelines Panel Systematic Review.

    Science.gov (United States)

    Soukup, Viktor; Čapoun, Otakar; Cohen, Daniel; Hernández, Virginia; Babjuk, Marek; Burger, Max; Compérat, Eva; Gontero, Paolo; Lam, Thomas; MacLennan, Steven; Mostafid, A Hugh; Palou, Joan; van Rhijn, Bas W G; Rouprêt, Morgan; Shariat, Shahrokh F; Sylvester, Richard; Yuan, Yuhong; Zigeuner, Richard

    2017-11-01

    Tumour grade is an important prognostic indicator in non-muscle-invasive bladder cancer (NMIBC). Histopathological classifications are limited by interobserver variability (reproducibility), which may have prognostic implications. European Association of Urology NMIBC guidelines suggest concurrent use of both 1973 and 2004/2016 World Health Organization (WHO) classifications. To compare the prognostic performance and reproducibility of the 1973 and 2004/2016 WHO grading systems for NMIBC. A systematic literature search was undertaken incorporating Medline, Embase, and the Cochrane Library. Studies were critically appraised for risk of bias (QUIPS). For prognosis, the primary outcome was progression to muscle-invasive or metastatic disease. Secondary outcomes were disease recurrence, and overall and cancer-specific survival. For reproducibility, the primary outcome was interobserver variability between pathologists. Secondary outcome was intraobserver variability (repeatability) by the same pathologist. Of 3593 articles identified, 20 were included in the prognostic review; three were eligible for the reproducibility review. Increasing tumour grade in both classifications was associated with higher disease progression and recurrence rates. Progression rates in grade 1 patients were similar to those in low-grade patients; progression rates in grade 3 patients were higher than those in high-grade patients. Survival data were limited. Reproducibility of the 2004/2016 system was marginally better than that of the 1973 system. Two studies on repeatability showed conflicting results. Most studies had a moderate to high risk of bias. Current grading classifications in NMIBC are suboptimal. The 1973 system identifies more aggressive tumours. Intra- and interobserver variability was slightly less in the 2004/2016 classification. We could not confirm that the 2004/2016 classification outperforms the 1973 classification in prediction of recurrence and progression. This article

  18. Open conversion during minimally invasive radical prostatectomy: impact on perioperative complications and predictors from national data.

    Science.gov (United States)

    Sharma, Vidit; Meeks, Joshua J

    2014-12-01

    Despite the increased use of minimally invasive radical prostatectomy, open conversion may occur due to surgical complications, surgeon inexperience or failure to progress. We used nationally representative data to quantify the impact of open conversion compared to nonconverted minimally invasive radical prostatectomy and open radical prostatectomy, and identify predictors of open conversion. Years 2004 to 2010 of the Nationwide Inpatient Sample were queried for patients who underwent radical prostatectomy to analyze the association of open conversion during minimally invasive radical prostatectomy with Clavien complications. Multivariate regression models yielded significant predictors of open conversion. From 2004 to 2010, 134,398 (95% CI 111,509-157,287) minimally invasive radical prostatectomies were performed with a 1.8% (95% CI 1.4-2.1) open conversion rate, translating to 2,360 (95% CI 2,001-2,720) conversions. Open conversion cases had a longer length of stay (4.17 vs 1.71 days, p open conversion cases 45.2% experienced a complication vs 7.2% and 12.9% of minimally invasive radical prostatectomy and open radical prostatectomy cases, respectively (p open conversion was associated with significantly increased odds of a Clavien grade 1, 2, 3 and 4 complication compared to nonconverted minimally invasive radical prostatectomy and open radical prostatectomy (OR range 2.913 to 15.670, p open conversion were obesity (OR 1.916), adhesions (OR 3.060), anemia (OR 5.692) and surgeon volume for minimally invasive radical prostatectomy less than 25 cases per year (OR 7.376) (all p Open conversion during minimally invasive radical prostatectomy is associated with a higher than expected increase in complications compared to open radical prostatectomy and minimally invasive radical prostatectomy after adjusting for age and comorbidities. External validation of predictors of open conversion may prove useful in minimizing open conversion during minimally invasive radical

  19. ErbB receptors and cell polarity: New pathways and paradigms for understanding cell migration and invasion

    International Nuclear Information System (INIS)

    Feigin, Michael E.; Muthuswamy, Senthil K.

    2009-01-01

    The ErbB family of receptor tyrosine kinases is involved in initiation and progression of a number of human cancers, and receptor activation or overexpression correlates with poor patient survival. Research over the past two decades has elucidated the molecular mechanisms underlying ErbB-induced tumorigenesis, which has resulted in the development of effective targeted therapies. ErbB-induced signal transduction cascades regulate a wide variety of cell processes, including cell proliferation, apoptosis, cell polarity, migration and invasion. Within tumors, disruption of these core processes, through cooperative oncogenic lesions, results in aggressive, metastatic disease. This review will focus on the ErbB signaling networks that regulate migration and invasion and identify a potential role for cell polarity pathways during cancer progression

  20. Complex Multi-Block Analysis identifies new immunologic and genetic disease progression patterns associated with the Residual β-Cell function 1 year after diagnosis of Type 1 Diabetes

    DEFF Research Database (Denmark)

    Andersen, Marie Louise Max; Rasmussen, Morten Arendt; Pörksen, Sven

    2013-01-01

    The purpose of the present study is to explore the progression of type 1 diabetes (T1D) in Danish children 12 months after diagnosis using Latent Factor Modelling. We include three data blocks of dynamic paraclinical biomarkers, baseline clinical characteristics and genetic profiles of diabetes r...

  1. Progressive Business

    DEFF Research Database (Denmark)

    Christiansen, Christian O.

    2016-01-01

    Guest Post to the Society for U.S. Intellectual History Blog. Brief introduction to the book Progressive Business: An Intellectual History of the Role of Business in American Society, Oxford U.P., 2015.......Guest Post to the Society for U.S. Intellectual History Blog. Brief introduction to the book Progressive Business: An Intellectual History of the Role of Business in American Society, Oxford U.P., 2015....

  2. Ecology of forest insect invasions

    Science.gov (United States)

    E.G. Brockerhoff; A.M. Liebhold

    2017-01-01

    Forests in virtually all regions of the world are being affected by invasions of non-native insects. We conducted an in-depth review of the traits of successful invasive forest insects and the ecological processes involved in insect invasions across the universal invasion phases (transport and arrival, establishment, spread and impacts). Most forest insect invasions...

  3. Cryptic invasions: a review

    Czech Academy of Sciences Publication Activity Database

    Morais, Pedro Miguel; Reichard, Martin

    613-614, February (2018), s. 1438-1448 ISSN 0048-9697 R&D Projects: GA ČR GA13-05872S Institutional support: RVO:68081766 Keywords : Conspecific invader * Biological invasions * Bibliometric * Invasiveness Subject RIV: EG - Zoology OBOR OECD: Environmental science s (social aspects to be 5.7) Impact factor: 4.900, year: 2016

  4. Is Switzerland suitable for the invasion of Aedes albopictus [corrected]?

    Science.gov (United States)

    Neteler, Markus; Metz, Markus; Rocchini, Duccio; Rizzoli, Annapaola; Flacio, Eleonora; Engeler, Luca; Guidi, Valeria; Lüthy, Peter; Tonolla, Mauro

    2013-01-01

    Over the last 30 years, the Asian tiger mosquito, Aedes albopictus, has rapidly spread around the world. The European distribution comprises the Mediterranean basin with a first appearance in Switzerland in 2003. Early identification of the most suitable areas in Switzerland allowing progressive invasion by this species is considered crucial to suggest adequate surveillance and control plans. We identified the most suitable areas for invasion and establishment of Ae. albopictus in Switzerland. The potential distribution areas linked to the current climatic suitability were assessed using remotely sensed land surface temperature data recorded by the MODIS satellite sensors. Suitable areas for adult survival and overwintering of diapausing eggs were also identified for future climatic conditions, considering two different climate change scenarios (A1B, A2) for the periods 2020-2049 and 2045-2074. At present, the areas around Lake Geneva in western Switzerland provide suitable climatic conditions for Ae. albopictus. In northern Switzerland, parts of the Rhine valley, around Lake Constance, as well as the surroundings of Lake Neuchâtel, appear to be suitable for the survival at least of adult Ae. albopictus. However, these areas are characterized by winters currently being too cold for survival and development of diapausing eggs. In southern Switzerland, Ae. albopictus is already well-established, especially in the Canton of Ticino. For the years 2020-2049, the predicted possible spread of the tiger mosquito does not differ significantly from its potential current distribution. However, important expansions are obtained if the period is extended to the years 2045-2074, when Ae. albopictus may invade large new areas. Several parts of Switzerland provide suitable climatic conditions for invasion and establishment of Ae. albopictus. The current distribution and rapid spread in other European countries suggest that the tiger mosquito will colonize new areas in Switzerland

  5. Is Switzerland Suitable for the Invasion of Aedes albopictus?

    Science.gov (United States)

    Neteler, Markus; Metz, Markus; Rocchini, Duccio; Rizzoli, Annapaola; Flacio, Eleonora; Engeler, Luca; Guidi, Valeria; Lüthy, Peter; Tonolla, Mauro

    2013-01-01

    Background Over the last 30 years, the Asian tiger mosquito, Aedes albopictus, has rapidly spread around the world. The European distribution comprises the Mediterranean basin with a first appearance in Switzerland in 2003. Early identification of the most suitable areas in Switzerland allowing progressive invasion by this species is considered crucial to suggest adequate surveillance and control plans. Methodology/Principal Findings We identified the most suitable areas for invasion and establishment of Ae. albopictus in Switzerland. The potential distribution areas linked to the current climatic suitability were assessed using remotely sensed land surface temperature data recorded by the MODIS satellite sensors. Suitable areas for adult survival and overwintering of diapausing eggs were also identified for future climatic conditions, considering two different climate change scenarios (A1B, A2) for the periods 2020–2049 and 2045–2074. At present, the areas around Lake Geneva in western Switzerland provide suitable climatic conditions for Ae. albopictus. In northern Switzerland, parts of the Rhine valley, around Lake Constance, as well as the surroundings of Lake Neuchâtel, appear to be suitable for the survival at least of adult Ae. albopictus. However, these areas are characterized by winters currently being too cold for survival and development of diapausing eggs. In southern Switzerland, Ae. albopictus is already well-established, especially in the Canton of Ticino. For the years 2020–2049, the predicted possible spread of the tiger mosquito does not differ significantly from its potential current distribution. However, important expansions are obtained if the period is extended to the years 2045–2074, when Ae. albopictus may invade large new areas. Conclusions/Significance Several parts of Switzerland provide suitable climatic conditions for invasion and establishment of Ae. albopictus. The current distribution and rapid spread in other European

  6. Modeling tumor invasion and metastasis in Drosophila

    Directory of Open Access Journals (Sweden)

    Wayne O. Miles

    2011-11-01

    Full Text Available Conservation of major signaling pathways between humans and flies has made Drosophila a useful model organism for cancer research. Our understanding of the mechanisms regulating cell growth, differentiation and development has been considerably advanced by studies in Drosophila. Several recent high profile studies have examined the processes constraining the metastatic growth of tumor cells in fruit fly models. Cell invasion can be studied in the context of an in vivo setting in flies, enabling the genetic requirements of the microenvironment of tumor cells undergoing metastasis to be analyzed. This Perspective discusses the strengths and limitations of Drosophila models of cancer invasion and the unique tools that have enabled these studies. It also highlights several recent reports that together make a strong case for Drosophila as a system with the potential for both testing novel concepts in tumor progression and cell invasion, and for uncovering players in metastasis.

  7. Five potential consequences of climate change for invasive species.

    Science.gov (United States)

    Hellmann, Jessica J; Byers, James E; Bierwagen, Britta G; Dukes, Jeffrey S

    2008-06-01

    Scientific and societal unknowns make it difficult to predict how global environmental changes such as climate change and biological invasions will affect ecological systems. In the long term, these changes may have interacting effects and compound the uncertainty associated with each individual driver. Nonetheless, invasive species are likely to respond in ways that should be qualitatively predictable, and some of these responses will be distinct from those of native counterparts. We used the stages of invasion known as the "invasion pathway" to identify 5 nonexclusive consequences of climate change for invasive species: (1) altered transport and introduction mechanisms, (2) establishment of new invasive species, (3) altered impact of existing invasive species, (4) altered distribution of existing invasive species, and (5) altered effectiveness of control strategies. We then used these consequences to identify testable hypotheses about the responses of invasive species to climate change and provide suggestions for invasive-species management plans. The 5 consequences also emphasize the need for enhanced environmental monitoring and expanded coordination among entities involved in invasive-species management.

  8. Synchronous lobular carcinoma in situ and invasive lobular cancer: marker or precursor for invasive lobular carcinoma.

    Science.gov (United States)

    Wallace, A S; Xiang, D; Hockman, L; Arya, M; Jeffress, J; Wang, Z; Dale, P S

    2014-10-01

    Lobular carcinoma in situ (LCIS) is a known risk factor for invasive breast carcinoma, but there is increasing data indicating a possible precursor relationship. This study investigates the incidence of lobular carcinoma in situ that occurs with invasive lobular carcinoma (ILC). Women diagnosed with ILC or LCIS from 2000 to 2010 were retrospectively identified and reviewed after institutional review board approval. This group was divided into two cohorts: ILC alone, and LCIS and ILC (ILC/LCIS). Patient demographics, disease characteristics, and treatment modalities were captured. p invasive ductal carcinoma at ∼40%. The association of pre-invasive and invasive lobular lesions should be further studied in a large scale prospective study to assess for a precursor relationship. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. The social dimensions of invasive plants.

    Science.gov (United States)

    Head, Lesley

    2017-06-06

    Invasive plants pose a major environmental management issue. Research into the social dimensions of this issue has flourished over the past decade, as part of the critical examination of relations between human and nonhuman worlds. The social sciences and humanities have made substantial contributions to conceptualizing invasiveness and nativeness; understanding the perceptions, attitudes and values of diverse stakeholders; and analysing the politics and practices of invasive plant management. Cultural analysis allows areas of conflict and commonality to be identified. Social complexity must be added to ecological complexity to understand the causal relationships underlying invasions; and linear understandings of science-policy relationships are too simplistic. Productive connections have been established between recent social and natural science approaches in the context of rapid environmental change and unpredictable futures. Nonetheless, the prevalence of human exceptionalism in the ecological sciences constitutes a major point of divergence between social and natural science perspectives.

  10. The assessment of angiogenesis and fibroblastic stromagenesis in hyperplastic and pre-invasive breast lesions

    Directory of Open Access Journals (Sweden)

    Louvrou Niki

    2008-04-01

    Full Text Available Abstract Background To investigate the changes of the neoplastic microenvironment during the different morphological alterations of hyperplastic and pre-invasive breast lesions. Methods 78 in situ ductal carcinomas of all degrees of differentiation, 22 atypical ductal hyperplasias, 25 in situ lobular carcinomas, 18 atypical lobular hyperplasias, 32 ductal epithelial hyperplasias of usual type and 8 flat atypias were immunohistochemically investigated for the expression of vascular endothelial growth factor (VEGF, smooth muscle actin (SMA and CD34, while microvessel density (MVD was counted using the anti-CD31 antibody. Results VEGF expression was strongly correlated with MVD in all hyperplastic and pre-invasive breast lesions (p Conclusion Angiogenesis is observed before any significant fibroblastic stromagenesis in pre-invasive breast lesions. A composite phenotype characterized by VEGF positive epithelial cells and SMA positive/CD34 negative stromal cells, is identified mostly in intermediate and high grade DCIS. These findings might imply for new therapeutic strategies using both anti-angiogenic factors and factors selectively targeting tumor stroma in order to prevent the progression of DCIS to invasive carcinoma.

  11. ANDROGENS REGULATE T47D CELLS MOTILITY AND INVASION THROUGH ACTIN CYTOSKELETON REMODELLING

    Directory of Open Access Journals (Sweden)

    Maria Magdalena Montt-Guevara

    2016-09-01

    Full Text Available The relationship between androgens and breast cancer is controversial. Androgens have complex effects on breast cancer progression and metastasis. Moreover, androgens receptor (AR is expressed in approximately 70% to 90% of invasive breast carcinomas, which has prognostic relevance in basal-like cancers and in triple negative breast cancers. Recent studies have associated the actin-binding proteins of the Ezrin-Radixin-Moesin (ERM family with metastasis in endocrine-sensitive cancers. We studied on T47D breast cancer cells whether androgens with different characteristics, such as testosterone (T, dihydrotestosterone (DHT and dehydroepiandrosterone (DHEA may regulate breast cancer cell motility and invasion through the control of actin remodelling. We demonstrate that androgens promote migration and invasion in T47D via Moesin activation. We show that T and DHEA exert their actions via the AR and estrogen receptor (ER, while the non aromatizable androgen – DHT only recruits AR. We further report that androgen induced significant changes in actin organization with pseudopodia along with membrane ruffles formation, and this process is mediated by Moesin. Our work identifies novel mechanisms of action of androgens on breast cancer cells. Through the modulation of Moesin, androgens alter the architecture of cytoskeleton in T47D breast cancer cell and promote cell migration and invasion. These results could help to understand the biological actions of androgens on breast cancer, and eventually to develop new strategies for treatment of breast cancer.

  12. Androgens Regulate T47D Cells Motility and Invasion through Actin Cytoskeleton Remodeling.

    Science.gov (United States)

    Montt-Guevara, Maria Magdalena; Shortrede, Jorge Eduardo; Giretti, Maria Silvia; Giannini, Andrea; Mannella, Paolo; Russo, Eleonora; Genazzani, Alessandro David; Simoncini, Tommaso

    2016-01-01

    The relationship between androgens and breast cancer is controversial. Androgens have complex effects on breast cancer progression and metastasis. Moreover, androgen receptor (AR) is expressed in approximately 70 to 90% of invasive breast carcinomas, which has prognostic relevance in basal-like cancers and in triple-negative breast cancers. Recent studies have associated the actin-binding proteins of the ezrin-radixin-moesin (ERM) family with metastasis in endocrine-sensitive cancers. We studied on T47D breast cancer cells whether androgens with different characteristics, such as testosterone (T), dihydrotestosterone (DHT), and dehydroepiandrosterone (DHEA) may regulate breast cancer cell motility and invasion through the control of actin remodeling. We demonstrate that androgens promote migration and invasion in T47D via Moesin activation. We show that T and DHEA exert their actions via the AR and estrogen receptor (ER), while the non-aromatizable androgen - DHT - only recruits AR. We further report that androgen induced significant changes in actin organization with pseudopodia along with membrane ruffles formation, and this process is mediated by Moesin. Our work identifies novel mechanisms of action of androgens on breast cancer cells. Through the modulation of Moesin, androgens alter the architecture of cytoskeleton in T47D breast cancer cell and promote cell migration and invasion. These results could help to understand the biological actions of androgens on breast cancer and, eventually, to develop new strategies for breast cancer treatment.

  13. The Role of Hypoxia in Glioblastoma Invasion

    Directory of Open Access Journals (Sweden)

    Ana Rita Monteiro

    2017-11-01

    Full Text Available Glioblastoma multiforme (GBM, a grade IV astrocytoma, is the most common and deadly type of primary malignant brain tumor, with a patient’s median survival rate ranging from 15 to 17 months. The current treatment for GBM involves tumor resection surgery based on MRI image analysis, followed by radiotherapy and treatment with temozolomide. However, the gradual development of tumor resistance to temozolomide is frequent in GBM patients leading to subsequent tumor regrowth/relapse. For this reason, the development of more effective therapeutic approaches for GBM is of critical importance. Low tumor oxygenation, also known as hypoxia, constitutes a major concern for GBM patients, since it promotes cancer cell spreading (invasion into the healthy brain tissue in order to evade this adverse microenvironment. Tumor invasion not only constitutes a major obstacle to surgery, radiotherapy, and chemotherapy, but it is also the main cause of death in GBM patients. Understanding how hypoxia triggers the GBM cells to become invasive is paramount to developing novel and more effective therapies against this devastating disease. In this review, we will present a comprehensive examination of the available literature focused on investigating how GBM hypoxia triggers an invasive cancer cell phenotype and the role of these invasive proteins in GBM progression.

  14. Cancer stem cell contribution to glioblastoma invasiveness.

    Science.gov (United States)

    Ortensi, Barbara; Setti, Matteo; Osti, Daniela; Pelicci, Giuliana

    2013-02-28

    Glioblastoma (GBM) is the most aggressive and lethal brain tumor in adults. Its invasive nature currently represents the most challenging hurdle to surgical resection. The mechanism adopted by GBM cells to carry out their invasive strategy is an intricate program that recalls what takes place in embryonic cells during development and in carcinoma cells during metastasis formation, the so-called epithelial-to-mesenchymal transition. GBM cells undergo a series of molecular and conformational changes shifting the tumor toward mesenchymal traits, including extracellular matrix remodeling, cytoskeletal re-patterning, and stem-like trait acquisition. A deeper understanding of the mechanisms driving the whole infiltrative process represents the first step toward successful treatment of this pathology. Here, we review recent findings demonstrating the invasive nature of GBM cancer stem cells, together with novel candidate molecules associated with both cancer stem cell biology and GBM invasion, like doublecortin and microRNAs. These findings may affect the design of effective therapies currently not considered for GBM invasive progression.

  15. Minimal Invasive Urologic Surgery and Postoperative Ileus

    Directory of Open Access Journals (Sweden)

    Fouad Aoun

    2015-07-01

    Full Text Available Postoperative ileus (POI is the most common cause of prolonged length of hospital stays (LOS and associated healthcare costs. The advent of minimal invasive technique was a major breakthrough in the urologic landscape with great potential to progress in the future. In the field of gastrointestinal surgery, several studies had reported lower incidence rates for POI following minimal invasive surgery compared to conventional open procedures. In contrast, little is known about the effect of minimal invasive approach on the recovery of bowel motility after urologic surgery. We performed an overview of the potential benefit of minimal invasive approach on POI for urologic procedures. The mechanisms and risk factors responsible for the onset of POI are discussed with emphasis on the advantages of minimal invasive approach. In the urologic field, POI is the main complication following radical cystectomy but it is rarely of clinical significance for other minimal invasive interventions. Laparoscopy or robotic assisted laparoscopic techniques when studied individually may reduce to their own the duration and prevent the onset of POI in a subset of procedures. The potential influence of age and urinary diversion type on postoperative ileus is contradictory in the literature. There is some evidence suggesting that BMI, blood loss, urinary extravasation, existence of a major complication, bowel resection, operative time and transperitoneal approach are independent risk factors for POI. Treatment of POI remains elusive. One of the most important and effective management strategies for patients undergoing radical cystectomy has been the development and use of enhanced recovery programs. An optimal rational strategy to shorten the duration of POI should incorporate minimal invasive approach when appropriate into multimodal fast track programs designed to reduce POI and shorten LOS.

  16. Invasion biology of thrips.

    Science.gov (United States)

    Morse, Joseph G; Hoddle, Mark S

    2006-01-01

    Thrips are among the stealthiest of insect invaders due to their small size and cryptic habits. Many invasive thrips are notorious for causing extensive crop damage, vectoring viral diseases, and permanently destabilizing IPM systems owing to irruptive outbreaks that require remediation with insecticides, leading to the development of insecticide resistance. Several challenges surface when attempting to manage incursive thrips species. Foremost among these is early recognition, followed by rapid and accurate identification of emergent pest species, elucidation of the region of origin, development of a management program, and the closing of conduits for global movement of thrips. In this review, we examine factors facilitating invasion by thrips, damage caused by these insects, pre- and post-invasion management tactics, and challenges looming on the horizon posed by invasive Thysanoptera, which continually challenge the development of sustainable management practices.

  17. Modelling Hotspots for Invasive Alien Plants in India.

    Science.gov (United States)

    Adhikari, Dibyendu; Tiwary, Raghuvar; Barik, Saroj Kanta

    2015-01-01

    Identification of invasion hotspots that support multiple invasive alien species (IAS) is a pre-requisite for control and management of invasion. However, till recently it remained a methodological challenge to precisely determine such invasive hotspots. We identified the hotspots of alien species invasion in India through Ecological Niche Modelling (ENM) using species occurrence data from the Global Biodiversity Information Facility (GBIF). The predicted area of invasion for selected species were classified into 4 categories based on number of model agreements for a region i.e. high, medium, low and very low. About 49% of the total geographical area of India was predicted to be prone to invasion at moderate to high levels of climatic suitability. The intersection of anthropogenic biomes and ecoregions with the regions of 'high' climatic suitability was classified as hotspot of alien plant invasion. Nineteen of 47 ecoregions of India, harboured such hotspots. Most ecologically sensitive regions of India, including the 'biodiversity hotspots' and coastal regions coincide with invasion hotspots, indicating their vulnerability to alien plant invasion. Besides demonstrating the usefulness of ENM and open source data for IAS management, the present study provides a knowledge base for guiding the formulation of an effective policy and management strategy for controlling the invasive alien species.

  18. The role thermal physiology plays in species invasion

    Science.gov (United States)

    Kelley, Amanda L.

    2014-01-01

    The characterization of physiological phenotypes that may play a part in the establishment of non-native species can broaden our understanding about the ecology of species invasion. Here, an assessment was carried out by comparing the responses of invasive and native species to thermal stress. The goal was to identify physiological patterns that facilitate invasion success and to investigate whether these traits are widespread among invasive ectotherms. Four hypotheses were generated and tested using a review of the literature to determine whether they could be supported across taxonomically diverse invasive organisms. The four hypotheses are as follows: (i) broad geographical temperature tolerances (thermal width) confer a higher upper thermal tolerance threshold for invasive rather than native species; (ii) the upper thermal extreme experienced in nature is more highly correlated with upper thermal tolerance threshold for invasive vs. native animals; (iii) protein chaperone expression—a cellular mechanism that underlies an organism's thermal tolerance threshold—is greater in invasive organisms than in native ones; and (iv) acclimation to higher temperatures can promote a greater range of thermal tolerance for invasive compared with native species. Each hypothesis was supported by a meta-analysis of the invasive/thermal physiology literature, providing further evidence that physiology plays a substantial role in the establishment of invasive ectotherms. PMID:27293666

  19. Identifying sarcopenia.

    Science.gov (United States)

    Abellan van Kan, Gabor; Houles, Mathieu; Vellas, Bruno

    2012-09-01

    The present review describes and discusses the currently available definitions for sarcopenia from consensus studies. Different sarcopenia definitions have been proposed in these last years. Six main approaches to an operative definition of sarcopenia have been identified. Although the first definitions were solely based on the assessment of the amount of muscle mass, current definitions seem to consistently recognize a bi-dimensional nature of sarcopenia. So, these approaches imply the need of simultaneously assessing both age-related quantitative (i.e. amount of muscle mass) and qualitative (i.e. muscle strength and function) declines of skeletal muscle. Although current consensus exists about a bi-dimensional nature, the proposed approaches to measure sarcopenia are characterized by methodological differences. The majority of the operative definitions proposes to assess muscle mass as an index of appendicular muscle mass divided by squared height (evaluated by dual energy X-ray absorptiometry), assess strength using hand-held dynamometers, and assess function by evaluating gait speed at habitual pace over a short distance. Nevertheless, the clinically relevant thresholds and how to combine the three aspects in an operative definition in order to identify sarcopenia are heterogeneous. A main drawback is that supportive empirical data are missing for these conceptual definitions regarding the risk-assessment of different clinically significant adverse outcomes.

  20. The Technological Development of Minimally Invasive Spine Surgery

    Science.gov (United States)

    Snyder, Laura A.; O'Toole, John; Eichholz, Kurt M.; Perez-Cruet, Mick J.; Fessler, Richard

    2014-01-01

    Minimally invasive spine surgery has its roots in the mid-twentieth century with a few surgeons and a few techniques, but it has now developed into a large field of progressive spinal surgery. A wide range of techniques are now called “minimally invasive,” and case reports are submitted constantly with new “minimally invasive” approaches to spinal pathology. As minimally invasive spine surgery has become more mainstream over the past ten years, in this paper we discuss its history and development. PMID:24967347

  1. Genomic comparison of invasive and rare non-invasive strains reveals Porphyromonas gingivalis genetic polymorphisms

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    Svetlana Dolgilevich

    2011-03-01

    Full Text Available Porphyromonas gingivalis strains are shown to invade human cells in vitro with different invasion efficiencies, varying by up to three orders of magnitude.We tested the hypothesis that invasion-associated interstrain genomic polymorphisms are present in P. gingivalis and that putative invasion-associated genes can contribute to P. gingivalis invasion.Using an invasive (W83 and the only available non-invasive P. gingivalis strain (AJW4 and whole genome microarrays followed by two separate software tools, we carried out comparative genomic hybridization (CGH analysis.We identified 68 annotated and 51 hypothetical open reading frames (ORFs that are polymorphic between these strains. Among these are surface proteins, lipoproteins, capsular polysaccharide biosynthesis enzymes, regulatory and immunoreactive proteins, integrases, and transposases often with abnormal GC content and clustered on the chromosome. Amplification of selected ORFs was used to validate the approach and the selection. Eleven clinical strains were investigated for the presence of selected ORFs. The putative invasion-associated ORFs were present in 10 of the isolates. The invasion ability of three isogenic mutants, carrying deletions in PG0185, PG0186, and PG0982 was tested. The PG0185 (ragA and PG0186 (ragB mutants had 5.1×103-fold and 3.6×103-fold decreased in vitro invasion ability, respectively.The annotation of divergent ORFs suggests deficiency in multiple genes as a basis for P. gingivalis non-invasive phenotype. Access the supplementary material to this article: Supplement, table (see Supplementary files under Reading Tools online.

  2. Caspofungin therapy of neonates with invasive candidiasis.

    Science.gov (United States)

    Odio, Carla M; Araya, Roberto; Pinto, Luis E; Castro, Carlos E; Vasquez, Sergio; Alfaro, Braulio; Sàenz, Alberto; Herrera, Marco L; Walsh, Thomas J

    2004-12-01

    Invasive candidiasis is an increasing problem in neonatal intensive care units worldwide and is an important cause of morbidity, mortality and prolongation of hospital stay. Despite administration of amphotericin B, invasive candidiasis in neonates is sometimes complicated by persistent fungemia and refractory invasive candidiasis. The problem has been augmented by the increasing prevalence of non-albicans species that often are resistant to fluconazole and to amphotericin B. The population consisted of 1 term and 9 premature neonates with invasive candidiasis caused by Candida albicans (n = 4), Candida parapsilosis (n = 3), Candida tropicalis (n = 2) and Candida glabrata (n = 1). Despite initial therapy with deoxycholate amphotericin B, blood cultures remained positive in all patients for 13-49 days. Invasive candidiasis progressed to meningitis and enlarging renal Candida bezoars in the kidney of one patient and an enlarging atrial vegetation in another. Another patient developed severe hypokalemia refractory to potassium supplementation. Two of the C. albicans and all of the non-albicans Candida isolates were resistant to fluconazole; the C. glabrata isolate was resistant to amphotericin B. Amphotericin B was discontinued and caspofungin initiated in all patients in a dosage of 1 mg/kg/d for 2 days followed by 2 mg/kg/d. All positive blood cultures cleared between 3 and 7 days after initiation of caspofungin, the atrial vegetation resolved and the renal Candida bezoars disappeared. Renal and hepatic function tests did not show any values above normal throughout caspofungin therapy. There were no attributable clinical adverse events during the administration of caspofungin in any of the patients. Caspofungin was effective, safe and well-tolerated as an alternative therapy for persistent and progressive candidiasis in those neonates who were unresponsive to or intolerant of deoxycholate amphotericin B.

  3. Invasive crayfish in the Pacific Northwest

    Science.gov (United States)

    Pearl, Christopher A.; McCreary, Brome; Adams, Michael

    2011-01-01

    Invasive species directly threaten freshwater biodiversity, particularly in regions of high aquatic richness like the Pacific Northwest (PNW). Crayfish are among the most impactful of aquatic invasive species. Invasive crayfish are considered ecosystem engineers due to their ability to alter basic wetland properties, such as reducing vegetation and bank integrity and increasing turbidity. In areas where invasion is advanced, crayfish pose major economic and ecological problems. Crayfish have been widely introduced for aquaculture and can become established in a wide range of habitat conditions. They also may be spread by anglers who use them as bait. Several non-native crayfish are established in the PNW, but the extent of their invasion is not well known. At least two groups are known from scattered sites in the PNW, and both have proven problematic for native species in other parts of the world: Red swamp crayfish (Procambarus clarkii) and several members of the genus Orconectes. Both groups are native to areas of the eastern United States. Both are identified globally as invasives of high concern and appear on the Oregon Department of Fish and Wildlife's "10 Most Unwanted" and the U.S. Forest Service's "Primary Species of Concern" lists for stream systems in the PNW. Despite the presence of introduced crayfish in the PNW and their high potential for negative effects, the scope of their invasion and effects on aquatic systems are not well known. The U.S. Geological Survey (USGS), along with local groups and state agencies, is working to clarify crayfish distribution and to outline which basins may not yet be invaded. Other goals are to improve understanding of habitat associations of invasive crayfish and their potential effects on native crayfish.

  4. Matrix-assisted laser desorption/ionization mass spectrometry imaging of cell cultures for the lipidomic analysis of potential lipid markers in human breast cancer invasion.

    Science.gov (United States)

    Wang, Shujuan; Chen, Xiaowu; Luan, Hemi; Gao, Dan; Lin, Shuhai; Cai, Zongwei; Liu, Jianjun; Liu, Hongxia; Jiang, Yuyang

    2016-02-28

    Breast cancer is the leading cause of cancer death among women worldwide. Identification of lipid targets that play a role in breast cancer invasion may advance our understanding of the rapid progression of cancer and may lead to the development of new biomarkers for the disease. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) was applied for the lipidomic profiling of two poorly invasive and two highly invasive breast cancer cell lines to identify the differentially accumulated lipids related to the invasive phenotype. The four cell lines were individually grown on indium tin oxide (ITO)-coated glass slides, analyzed as cell cultures. The raster width and matrix for detection were optimized to improve detection sensitivity. Optimized MSI measurements were performed directly on the cell culture with 9-aminoacridine as matrix, resulting in 215 endogenous compounds detected in positive ion mode and 267 endogenous compounds in negative ion mode in all the four cell lines, representing the largest group of analytes that have been analyzed from cells by a single MSI study. In highly invasive cell lines, 31 lipids including phosphatidylglycerol (PG) and phosphatidic acids were found upregulated and eight lipids including sphingomyelin (SM) downregulated in negative ion mode. The products of de novo fatty acid synthesis incorporated into membrane phospholipids, like oleic-acid-containing PG, may be involved in mitochondrial dysfunction and thus affect the invasion of breast cancer cells. The deficiency of SM may be related to the disruption of apoptosis in highly invasive cancer cells. This work uncovered more analytes in cells by MSI than previous reports, providing a better visualization and novel insights to advance our understanding of the relationship between rapid progression of breast cancer and lipid metabolism. The most altered lipids may aid the discovery of diagnostic markers and therapeutic targets of breast cancer. Copyright

  5. Membrane-type-3 matrix metalloproteinase (MT3-MMP functions as a matrix composition-dependent effector of melanoma cell invasion.

    Directory of Open Access Journals (Sweden)

    Olga Tatti

    Full Text Available In primary human melanoma, the membrane-type matrix metalloproteinase, MT3-MMP, is overexpressed in the most aggressive nodular-type tumors. Unlike MT1-MMP and MT2-MMP, which promote cell invasion through basement membranes and collagen type I-rich tissues, the function of MT3-MMP in tumor progression remains unclear. Here, we demonstrate that MT3-MMP inhibits MT1-MMP-driven melanoma cell invasion in three-dimensional collagen, while yielding an altered, yet MT1-MMP-dependent, form of expansive growth behavior that phenocopies the formation of nodular cell colonies. In melanoma cell lines originating from advanced primary or metastatic lesions, endogenous MT3-MMP expression was associated with limited collagen-invasive potential. In the cell lines with highest MT3-MMP expression relative to MT1-MMP, collagen-invasive activity was increased following stable MT3-MMP gene silencing. Consistently, MT3-MMP overexpression in cells derived from less advanced superficially spreading melanoma lesions, or in the MT3-MMP knockdown cells, reduced MT1-MMP-dependent collagen invasion. Rather than altering MT1-MMP transcription, MT3-MMP interacted with MT1-MMP in membrane complexes and reduced its cell surface expression. By contrast, as a potent fibrinolytic enzyme, MT3-MMP induced efficient invasion of the cells in fibrin, a provisional matrix component frequently found at tumor-host tissue interfaces and perivascular spaces of melanoma. Since MT3-MMP was significantly upregulated in biopsies of human melanoma metastases, these results identify MT3-MMP as a matrix-dependent modifier of the invasive tumor cell functions during melanoma progression.

  6. Insights into atherosclerosis from invasive and non-invasive imaging studies: Should we treat subclinical atherosclerosis?

    Science.gov (United States)

    Santos, Raul D; Nasir, Khurram

    2009-08-01

    Although atherosclerosis is associated with the elderly, young adults with hypercholesterolemia and other cardiovascular risk factors may have subclinical atherosclerotic disease. In many cases, when two or more risk factors are present, conventional risk assessment using the Framingham score, that was not designed to detect atherosclerotic plaques, may significantly underestimate the extent of atherosclerosis. Several non-invasive imaging technologies now make it possible to identify subclinical atherosclerosis before symptoms appear or major vascular events occur. These include B-mode ultrasound to measure carotid intima-media thickness, computed tomography to measure coronary artery calcification, and high-resolution magnetic resonance imaging to evaluate plaque size and composition. On the basis of available evidence, assessment of subclinical atherosclerosis should be considered in persons judged to be at intermediate risk by Framingham score, because test results may influence risk stratification and, consequently, the intensity of therapeutic intervention. Patients with significant subclinical atherosclerosis are at high risk and, like other high-risk individuals, should receive treatment designed to achieve aggressive low-density lipoprotein cholesterol targets. Clinical studies show that statin therapy may delay atherosclerosis progression and that intensive therapy with rosuvastatin may actually reverse the atherosclerotic process.

  7. miR-150-5p inhibits hepatoma cell migration and invasion by targeting MMP14.

    Directory of Open Access Journals (Sweden)

    Tao Li

    Full Text Available Hepatocellular carcinoma (HCC is one of the leading causes of cancer-related mortality worldwide. Despite progress in diagnostics and treatment of HCC, its prognosis remains poor because the molecular mechanisms underlying hepatocarcinogenesis are not well understood. In the study, we focused on identifying the role of miRNAs in HCC progression. miRNA microarray was used to analyze the differentially expressed miRNAs, and the results were validated by qPCR. We found that the miR-150-5p expression is down-regulated in HCC tissues compared with pair non-tumor tissues. miR-150-5p expression is also decreased in metastatic cancer tissues compared with pair primary tissues, indicating that miR-150-5p may be involved in HCC metastasis. Functionally, miR-150-5p inhibition significantly promotes hepatoma cell migration and invasion, whereas miR-150-5p overexpression suppresses cancer cell migration and invasion in vitro. The matrix metalloproteinase 14 (MMP14 is identified as a new target gene of miR-150-5p. miR-150-5p markedly inhibits MMP14 expression in hepatoma cells, and miR-150-5p expression is negative correlation with MMP14 expression in vivo. More important, re-expression of MMP14 in hepatoma cells partially reverses the effect of miR-150-5p in inhibiting cell invasion.

  8. Biological invasions, climate change and genomics.

    Science.gov (United States)

    Chown, Steven L; Hodgins, Kathryn A; Griffin, Philippa C; Oakeshott, John G; Byrne, Margaret; Hoffmann, Ary A

    2015-01-01

    The rate of biological invasions is expected to increase as the effects of climate change on biological communities become widespread. Climate change enhances habitat disturbance which facilitates the establishment of invasive species, which in turn provides opportunities for hybridization and introgression. These effects influence local biodiversity that can be tracked through genetic and genomic approaches. Metabarcoding and metagenomic approaches provide a way of monitoring some types of communities under climate change for the appearance of invasives. Introgression and hybridization can be followed by the analysis of entire genomes so that rapidly changing areas of the genome are identified and instances of genetic pollution monitored. Genomic markers enable accurate tracking of invasive species' geographic origin well beyond what was previously possible. New genomic tools are promoting fresh insights into classic questions about invading organisms under climate change, such as the role of genetic variation, local adaptation and climate pre-adaptation in successful invasions. These tools are providing managers with often more effective means to identify potential threats, improve surveillance and assess impacts on communities. We provide a framework for the application of genomic techniques within a management context and also indicate some important limitations in what can be achieved.

  9. SNAI2/Slug promotes growth and invasion in human gliomas

    International Nuclear Information System (INIS)

    Yang, Hong Wei; Menon, Lata G; Black, Peter M; Carroll, Rona S; Johnson, Mark D

    2010-01-01

    Numerous factors that contribute to malignant glioma invasion have been identified, but the upstream genes coordinating this process are poorly known. To identify genes controlling glioma invasion, we used genome-wide mRNA expression profiles of primary human glioblastomas to develop an expression-based rank ordering of 30 transcription factors that have previously been implicated in the regulation of invasion and metastasis in cancer. Using this approach, we identified the oncogenic transcriptional repressor, SNAI2/Slug, among the upper tenth percentile of invasion-related transcription factors overexpressed in glioblastomas. SNAI2 mRNA expression correlated with histologic grade and invasive phenotype in primary human glioma specimens, and was induced by EGF receptor activation in human glioblastoma cells. Overexpression of SNAI2/Slug increased glioblastoma cell proliferation and invasion in vitro and promoted angiogenesis and glioblastoma growth in vivo. Importantly, knockdown of endogenous SNAI2/Slug in glioblastoma cells decreased invasion and increased survival in a mouse intracranial human glioblastoma transplantation model. This genome-scale approach has thus identified SNAI2/Slug as a regulator of growth and invasion in human gliomas

  10. Introduced and invasive cactus species: a global review.

    Science.gov (United States)

    Novoa, Ana; Le Roux, Johannes J; Robertson, Mark P; Wilson, John R U; Richardson, David M

    2014-12-03

    Understanding which species are introduced and become invasive, and why, are central questions in invasion science. Comparative studies on model taxa have provided important insights, but much more needs to be done to unravel the context dependencies of these findings. The cactus family (Cactaceae), one of the most popular horticultural plant groups, is an interesting case study. Hundreds of cactus species have been introduced outside their native ranges; a few of them are among the most damaging invasive plant species in the world. We reviewed the drivers of introductions and invasions in the family and seek insights that can be used to minimize future risks. We compiled a list of species in the family and determined which have been recorded as invasive. We also mapped current global distributions and modelled the potential global distributions based on distribution data of known invasive taxa. Finally, we identified whether invasiveness is phylogenetically clustered for cacti and whether particular traits are correlated with invasiveness. Only 57 of the 1922 cactus species recognized in this treatment have been recorded as invasive. There are three invasion hotspots: South Africa (35 invasive species recorded), Australia (26 species) and Spain (24 species). However, there are large areas of the world with climates suitable for cacti that are at risk of future invasion-in particular, parts of China, eastern Asia and central Africa. The invasive taxa represent an interesting subset of the total species pool. There is a significant phylogenetic signal: invasive species occur in 2 of the 3 major phylogenetic clades and in 13 of the 130 genera. This phylogenetic signal is not driven by human preference, i.e. horticultural trade, but all invasive species are from 5 of the 12 cactus growth forms. Finally, invasive species tend to have significantly larger native ranges than non-invasive species, and none of the invasive species are of conservation concern in their

  11. Current standards and recent progress in minimally invasive Phlebo surgery

    Directory of Open Access Journals (Sweden)

    Oliver Göckeritz

    2012-01-01

    Full Text Available Venous disorders are among the most frequent disease patterns in the Western world. Still at the turn to the 21st century there was no alternative available to the surgical treatment of varicosis. Meanwhile the endoluminal treatment methods have established and have demonstrated their efficiency while having lower side effects in comparison to the traditional treatment, even though conservatively oriented surgeons are still skeptically eyeing these methods. In the US, according to the latest MRG report of 2011, about 95% of all venous surgeries are already done endoluminally. This paper offers an overview of prevailing treatment standards of the most important endoluminal therapy techniques and shows current trends.

  12. A Systems Biology Approach Identifies FUT8 as a Driver of Melanoma Metastasis.

    Science.gov (United States)

    Agrawal, Praveen; Fontanals-Cirera, Barbara; Sokolova, Elena; Jacob, Samson; Vaiana, Christopher A; Argibay, Diana; Davalos, Veronica; McDermott, Meagan; Nayak, Shruti; Darvishian, Farbod; Castillo, Mireia; Ueberheide, Beatrix; Osman, Iman; Fenyö, David; Mahal, Lara K; Hernando, Eva

    2017-06-12

    Association of aberrant glycosylation with melanoma progression is based mainly on analyses of cell lines. Here we present a systems-based study of glycomic changes and corresponding enzymes associated with melanoma metastasis in patient samples. Upregulation of core fucosylation (FUT8) and downregulation of α-1,2 fucosylation (FUT1, FUT2) were identified as features of metastatic melanoma. Using both in vitro and in vivo studies, we demonstrate FUT8 is a driver of melanoma metastasis which, when silenced, suppresses invasion and tumor dissemination. Glycoprotein targets of FUT8 were enriched in cell migration proteins including the adhesion molecule L1CAM. Core fucosylation impacted L1CAM cleavage and the ability of L1CAM to support melanoma invasion. FUT8 and its targets represent therapeutic targets in melanoma metastasis. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Progress risk assessment of oral premalignant lesions with saliva miRNA analysis

    International Nuclear Information System (INIS)

    Yang, Ya; Li, Yue-xiu; Yang, Xi; Jiang, Long; Zhou, Zuo-jun; Zhu, Ya-qin

    2013-01-01

    Oral cancer develops through multi-stages: from normal to mild (low grade) dysplasia (LGD), moderate dysplasia, and severe (high grade) dysplasia (HGD), to carcinoma in situ (CIS) and finally invasive oral squamous cell carcinomas (OSCC). Clinical and histological assessments are not reliable in predicting which precursor lesions will progress. The aim of this study was to assess the potential of a noninvasive approach to assess progress risk of oral precancerous lesions. We first used microRNA microarray to profile progressing LGD oral premaligant lesions (OPLs) from non-progressing LGD OPLs in order to explore the possible microRNAs deregulated in low grade OPLs which later progressed to HGD or OSCC. We then used RT-qPCR to detect miRNA targets from the microarray results in saliva samples of these patients. We identified a specific miRNA signature that is aberrantly expressed in progressing oral LGD leukoplakias. Similar expression patterns were detected in saliva samples from these patients. These results show promise for using saliva miRNA signature for monitoring of cancer precursor lesions and early detection of disease progression

  14. Epigenetic signatures of invasive status in populations of marine invertebrates

    Science.gov (United States)

    Ardura, Alba; Zaiko, Anastasija; Morán, Paloma; Planes, Serge; Garcia-Vazquez, Eva

    2017-02-01

    Epigenetics, as a DNA signature that affects gene expression and enables rapid reaction of an organism to environmental changes, is likely involved in the process of biological invasions. DNA methylation is an epigenetic mechanism common to plants and animals for regulating gene expression. In this study we show, for the first time in any marine species, significant reduction of global methylation levels during the expansive phase of a pygmy mussel (Xenostrobus securis) recent invasion in Europe (two-year old), while in older introductions such epigenetic signature of invasion was progressively reduced. Decreased methylation was interpreted as a rapid way of increasing phenotypic plasticity that would help invasive populations to thrive. This epigenetic signature of early invasion was stronger than the expected environmental signature of environmental stress in younger populations sampled from ports, otherwise detected in a much older population (>90 year old) of the also invasive tubeworm Ficopomatus enigmaticus established in similar locations. Higher epigenetic than genetic diversity found in X. securis was confirmed from F. enigmaticus samples. As reported for introduced plants and vertebrates, epigenetic variation could compensate for relatively lower genetic variation caused by founder effects. These phenomena were compared with epigenetic mechanisms involved in metastasis, as parallel processes of community (biological invasion) and organism (cancer) invasions.

  15. Emergent Minimally Invasive Esophagogastrectomy

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    Thomas Fabian

    2017-01-01

    Full Text Available Introduction. Esophageal perforation in the setting of a malignancy carries a high morbidity and mortality. We describe our management of such a patient using minimally invasive approach. Methods. An 83-year-old female presented with an iatrogenic esophageal perforation during the workup of dysphagia. She was referred for surgical evaluation immediately after the event which occurred in the endoscopy suite. Minimally invasive esophagectomy was chosen to provide definitive treatment for both her malignancy and esophageal perforation. Results. Following an uncomplicated operative course, she was eventually discharged to extended care for rehabilitation and remains alive four years after her resection. Conclusion. Although traditional open techniques are the accepted gold standard of treatment for esophageal perforation, minimally invasive esophagectomy plays an important role in experienced hands and may be offered to such patients.

  16. Progressivity Enhanced

    Directory of Open Access Journals (Sweden)

    Marko Hren

    2013-09-01

    Full Text Available Rather than a scientific text, the author contributes a concise memorandum from the originator of the idea who has managed the campaign for the conversion of the military barracks into a creative cluster between 1988 and 2002, when he parted ways with Metelkova due to conflicting views on the center’s future. His views shed light on a distant period of time from a perspective of a participant–observer. The information is abundantly supported by primary sources, also available online. However, some of the presented hypotheses are heavily influenced by his personal experiences of xenophobia, elitism, and predatorial behavior, which were already then discernible on the so-called alternative scene as well – so much so that they obstructed the implementation of progressive programs. The author claims that, in spite of the substantially different reality today, the myths and prejudices concerning Metelkova must be done away with in order to enhance its progressive nature. Above all, the paper calls for an objective view on internal antagonisms, mainly originating in deep class divisions between the users. These make a clear distinction between truly marginal ndividuals and the overambitious beau-bourgeois, as the author labels the large part of users of Metelkova of »his« time. On these grounds, he argues for a robust approach to ban all forms of xenophobia and self-ghettoization.

  17. Globally threatened vertebrates on islands with invasive species.

    Science.gov (United States)

    Spatz, Dena R; Zilliacus, Kelly M; Holmes, Nick D; Butchart, Stuart H M; Genovesi, Piero; Ceballos, Gerardo; Tershy, Bernie R; Croll, Donald A

    2017-10-01

    Global biodiversity loss is disproportionately rapid on islands, where invasive species are a major driver of extinctions. To inform conservation planning aimed at preventing extinctions, we identify the distribution and biogeographic patterns of highly threatened terrestrial vertebrates (classified by the International Union for Conservation of Nature) and invasive vertebrates on ~465,000 islands worldwide by conducting a comprehensive literature review and interviews with more than 500 experts. We found that 1189 highly threatened vertebrate species (319 amphibians, 282 reptiles, 296 birds, and 292 mammals) breed on 1288 islands. These taxa represent only 5% of Earth's terrestrial vertebrates and 41% of all highly threatened terrestrial vertebrates, which occur in invasive vertebrates was available for 1030 islands (80% of islands with highly threatened vertebrates). Invasive vertebrates were absent from 24% of these islands, where biosecurity to prevent invasions is a critical management tool. On the 76% of islands where invasive vertebrates were present, management could benefit 39% of Earth's highly threatened vertebrates. Invasive mammals occurred in 97% of these islands, with Rattus sp. as the most common invasive vertebrate (78%; 609 islands). Our results provide an important baseline for identifying islands for invasive species eradication and other island conservation actions that reduce biodiversity loss.

  18. Revealing historic invasion patterns and potential invasion sites for two non-native plant species.

    Directory of Open Access Journals (Sweden)

    Jacob N Barney

    Full Text Available The historical spatio-temporal distribution of invasive species is rarely documented, hampering efforts to understand invasion dynamics, especially at regional scales. Reconstructing historical invasions through use of herbarium records combined with spatial trend analysis and modeling can elucidate spreading patterns and identify susceptible habitats before invasion occurs. Two perennial species were chosen to contrast historic and potential phytogeographies: Japanese knotweed (Polygonum cuspidatum, introduced intentionally across the US; and mugwort (Artemisia vulgaris, introduced largely accidentally to coastal areas. Spatial analysis revealed that early in the invasion, both species have a stochastic distribution across the contiguous US, but east of the 90(th meridian, which approximates the Mississippi River, quickly spread to adjacent counties in subsequent decades. In contrast, in locations west of the 90(th meridian, many populations never spread outside the founding county, probably a result of encountering unfavorable environmental conditions. Regression analysis using variables categorized as environmental or anthropogenic accounted for 24% (Japanese knotweed and 30% (mugwort of the variation in the current distribution of each species. Results show very few counties with high habitat suitability (>/=80% remain un-invaded (5 for Japanese knotweed and 6 for mugwort, suggesting these perennials are reaching the limits of large-scale expansion. Despite differences in initial introduction loci and pathways, Japanese knotweed and mugwort demonstrate similar historic patterns of spread and show declining rates of regional expansion. Invasion mitigation efforts should be concentrated on areas identified as highly susceptible that border invaded regions, as both species demonstrate secondary expansion from introduction loci.

  19. Over-invasion by functionally equivalent invasive species.

    Science.gov (United States)

    Russell, James C; Sataruddin, Nurul S; Heard, Allison D

    2014-08-01

    Multiple invasive species have now established at most locations around the world, and the rate of new species invasions and records of new invasive species continue to grow. Multiple invasive species interact in complex and unpredictable ways, altering their invasion success and impacts on biodiversity. Incumbent invasive species can be replaced by functionally similar invading species through competitive processes; however the generalized circumstances leading to such competitive displacement have not been well investigated. The likelihood of competitive displacement is a function of the incumbent advantage of the resident invasive species and the propagule pressure of the colonizing invasive species. We modeled interactions between populations of two functionally similar invasive species and indicated the circumstances under which dominance can be through propagule pressure and incumbent advantage. Under certain circumstances, a normally subordinate species can be incumbent and reject a colonizing dominant species, or successfully colonize in competition with a dominant species during simultaneous invasion. Our theoretical results are supported by empirical studies of the invasion of islands by three invasive Rattus species. Competitive displacement is prominent in invasive rats and explains the replacement of R. exulans on islands subsequently invaded by European populations of R. rattus and R. norvegicus. These competition outcomes between invasive species can be found in a broad range of taxa and biomes, and are likely to become more common. Conservation management must consider that removing an incumbent invasive species may facilitate invasion by another invasive species. Under very restricted circumstances of dominant competitive ability but lesser impact, competitive displacement may provide a novel method of biological control.

  20. Progress report

    International Nuclear Information System (INIS)

    Brumovsky, M.

    1979-01-01

    Progress Report, covering the period up to the end of 1979 year, was sent to the IAEA according to the research agreement No. 1971 /CF. This work covered the following fields: preparation and dummy irradiation experiments with a new experimental capsule of ''CHOUCA-M'' type; measurement of temperature fields and design of specimen holders; measurement of neutron energy spectrum in the irradiation place in our experimental reactor of VVR-S type (Nuclear Research Institute) using a set of activation detectors; unification and calibration of the measurement of neutron fluence with the use of Fe, Cu, Mn-Mg and Co-Al monitors; development and improvement of the measuring apparatus and technique for the dynamic testing of pre-cracked specimens with determination of dynamic parameters of fracture mechanics; preparation and manufacture of testing specimens from the Japanese steels - forging, plate and weld metal; preparation of the irradiation capsule for assembling

  1. Exotic invasive plants

    Science.gov (United States)

    Carolyn Hull Sieg; Barbara G. Phillips; Laura P. Moser

    2003-01-01

    Ecosystems worldwide are threatened by nonnative plant invasions that can cause undesirable, irreversible changes. They can displace native plants and animals, out-cross with native flora, alter nutrient cycling and other ecosystem functions, and even change an ecosystem's flammability (Walker and Smith 1997). After habitat loss, the spread of exotic species is...

  2. Minimally invasive distal pancreatectomy

    NARCIS (Netherlands)

    Røsok, Bård I.; de Rooij, Thijs; van Hilst, Jony; Diener, Markus K.; Allen, Peter J.; Vollmer, Charles M.; Kooby, David A.; Shrikhande, Shailesh V.; Asbun, Horacio J.; Barkun, Jeffrey; Besselink, Marc G.; Boggi, Ugo; Conlon, Kevin; Han, Ho Seong; Hansen, Paul; Kendrick, Michael L.; Kooby, David; Montagnini, Andre L.; Palanivelu, Chinnasamy; Wakabayashi, Go; Zeh, Herbert J.

    2017-01-01

    The first International conference on Minimally Invasive Pancreas Resection was arranged in conjunction with the annual meeting of the International Hepato-Pancreato-Biliary Association (IHPBA), in Sao Paulo, Brazil on April 19th 2016. The presented evidence and outcomes resulting from the session

  3. Management of invasive species

    DEFF Research Database (Denmark)

    Schou, Jesper Sølver; Jensen, Frank

    In this paper, we conduct a number of cost-benefit analyses to clarify whether the establishment of invasive species should be prevented or the damage of such species should be mitigated after introduction. We use the potential establishment of ragweed in Denmark as an empirical case. The main...... of information externalities, altruistic preferences, possible catastrophic events and ethical considerations....

  4. Gene expression analyses of primary melanomas reveal CTHRC1 as an important player in melanoma progression

    Science.gov (United States)

    Eriksson, Johanna; Le Joncour, Vadim; Nummela, Pirjo; Jahkola, Tiina; Virolainen, Susanna; Laakkonen, Pirjo; Saksela, Olli; Hölttä, Erkki

    2016-01-01

    Melanoma is notorious for its high tendency to metastasize and its refractoriness to conventional treatments after metastasis, and the responses to most targeted therapies are short-lived. A better understanding of the molecular mechanisms behind melanoma development and progression is needed to develop more effective therapies and to identify new markers to predict disease behavior. Here, we compared the gene expression profiles of benign nevi, and non-metastatic and metastatic primary melanomas to identify any common changes in disease progression. We identified several genes associated with inflammation, angiogenesis, and extracellular matrix modification to be upregulated in metastatic melanomas. We selected one of these genes, collagen triple helix repeat containing 1 (CTHRC1), for detailed analysis, and found that CTHRC1 was expressed in both melanoma cells and the associated fibroblasts, as well as in the endothelium of tumor blood vessels. Knockdown of CTHRC1 expression by shRNAs in melanoma cells inhibited their migration in Transwell assays and their invasion in three-dimensional collagen and Matrigel matrices. We also elucidated the possible down-stream effectors of CTHRC1 by gene expression profiling of the CTHRC1-knockdown cells. Our analyses showed that CTHRC1 is regulated coordinately with fibronectin and integrin β3 by the pro-invasive and -angiogenic transcription factor NFATC2. We also found CTHRC1 to be a target of TFGβ and BRAF. These data highlight the importance of tumor stroma in melanoma progression. Furthermore, CTHRC1 was recognized as an important mediator of melanoma cell migration and invasion, providing together with its regulators—NFATC2, TGFβ, and BRAF—attractive therapeutic targets against metastatic melanomas. PMID:26918341

  5. The evolution of minimally invasive bariatric surgery.

    Science.gov (United States)

    Batchelder, Andrew J; Williams, Robert; Sutton, Christopher; Khanna, Achal

    2013-08-01

    Obesity is a pandemic associated with significant morbidity and mortality. This historical article charts the progress of successful strategies that have been used to tackle weight loss from dietary modifications to the development of surgical interventions that have subsequently evolved. It also provides a précis of the reported outcome data following minimally invasive bariatric procedures. A literature review was performed. All articles relevant to the progression of bariatric surgery and minimally invasive surgery were assessed, as were those articles that described the ultimate evolution, combination, and establishment of the two techniques. This article charts the progression of early weight loss strategies, from early dietary modifications and pharmacologic interventions to initial techniques in small bowel bypass procedures, banding techniques, and sleeve gastrectomies. It also describes the simultaneous developments of endoscopic interventions and laparoscopic procedures. A range of procedures are described, which differ in their success in terms of loss of excess weight and in their complication rates. Weight loss is greatest for biliopancreatic diversion followed by gastric bypass and sleeve gastrectomy and least for adjustable gastric banding. Bariatric surgery is an evolving field, which will continue to expand given current epidemiologic trends. Developments in instrumentation and surgical techniques, including single access and natural orifice approaches, may offer further benefit in terms of patient acceptability. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Applying remote sensing to invasive species science—A tamarisk example

    Science.gov (United States)

    Morisette, Jeffrey T.

    2011-01-01

    The Invasive Species Science Branch of the Fort Collins Science Center provides research and technical assistance relating to management concerns for invasive species, including understanding how these species are introduced, identifying areas vulnerable to invasion, forecasting invasions, and developing control methods. This fact sheet considers the invasive plant species tamarisk (Tamarix spp), addressing three fundamental questions: *Where is it now? *What are the potential or realized ecological impacts of invasion? *Where can it survive and thrive if introduced? It provides peer-review examples of how the U.S. Geological Survey, working with other federal agencies and university partners, are applying remote-sensing technologies to address these key questions.

  7. MYCN and HDAC5 transcriptionally repress CD9 to trigger invasion and metastasis in neuroblastoma

    NARCIS (Netherlands)

    Fabian, Johannes; Opitz, Desirée; Althoff, Kristina; Lodrini, Marco; Hero, Barbara; Volland, Ruth; Beckers, Anneleen; de Preter, Katleen; Decock, Anneleen; Patil, Nitin; Abba, Mohammed; Kopp-Schneider, Annette; Astrahantseff, Kathy; Wünschel, Jasmin; Pfeil, Sebastian; Ercu, Maria; Künkele, Annette; Hu, Jamie; Thole, Theresa; Schweizer, Leonille; Mechtersheimer, Gunhild; Carter, Daniel; Cheung, Belamy B.; Popanda, Odilia; von Deimling, Andreas; Koster, Jan; Versteeg, Rogier; Schwab, Manfred; Marshall, Glenn M.; Speleman, Frank; Erb, Ulrike; Zoeller, Margot; Allgayer, Heike; Simon, Thorsten; Fischer, Matthias; Kulozik, Andreas E.; Eggert, Angelika; Witt, Olaf; Schulte, Johannes H.; Deubzer, Hedwig E.

    2016-01-01

    The systemic and resistant nature of metastatic neuroblastoma renders it largely incurable with current multimodal treatment. Clinical progression stems mainly from the increasing burden of metastatic colonization. Therapeutically inhibiting the migration-invasion-metastasis cascade would be of

  8. Ridgefield Complex - Invasive Plant ED/RR Search 2015

    Data.gov (United States)

    Department of the Interior — The proposed project is a part of the Gorge NWRs’ invasives management program and will help achieve goals and improve targeted habitats identified in the Refuges’...

  9. Pattern recognition receptors and their role in invasive aspergillosis

    NARCIS (Netherlands)

    Gresnigt, M.S.; Netea, M.G.; van de Veerdonk, F.L.

    2012-01-01

    Pattern recognition receptors (PRRs) are germline receptors that recognize conserved structures on microorganisms. Several PRRs have been identified in the recent years that are involved in the immune response against Aspergillus fumigatus. The role of PRRs in invasive pulmonary aspergillosis

  10. Invasive Plants -- A Horticultural Perspective

    OpenAIRE

    Niemiera, Alexander Xavier, 1951-; Von Holle, Betsy

    2009-01-01

    This publication explains how nonnative invasive plants are harmful and why you should care, how to predict the invasive potential of a plant, and how gardeners and landscape professionals can make informed choices when choosing plants.

  11. BCG-unresponsive non-muscle-invasive bladder cancer: recommendations from the IBCG

    NARCIS (Netherlands)

    Kamat, A.M.; Colombel, M.; Sundi, D.; Lamm, D.; Boehle, A.; Brausi, M.; Buckley, R.; Persad, R.; Palou, J.; Soloway, M.; Witjes, J.A.

    2017-01-01

    Intravesical immunotherapy with live attenuated BCG remains the standard of care for patients with high-risk and intermediate-risk non-muscle-invasive bladder cancer (NMIBC). Most patients initially respond, but recurrence is frequent and progression to invasive cancer is a concern. No established

  12. Monitoring and Inhibiting MT1-MMP during Cancer Initiation and Progression

    Directory of Open Access Journals (Sweden)

    Sonia Pahwa

    2014-02-01

    Full Text Available Membrane-type 1 matrix metalloproteinase (MT1-MMP is a zinc-dependent type-I transmembrane metalloproteinase involved in pericellular proteolysis, migration and invasion. Numerous substrates and binding partners have been identified for MT1-MMP, and its role in collagenolysis appears crucial for tumor invasion. However, development of MT1-MMP inhibitors must consider the substantial functions of MT1-MMP in normal physiology and disease prevention. The present review examines the plethora of MT1-MMP activities, how these activities relate to cancer initiation and progression, and how they can be monitored in real time. Examination of MT1-MMP activities and cell surface behaviors can set the stage for the development of unique, selective MT1-MMP inhibitors.

  13. 78 FR 64909 - Southwestern Region: Invasive Plant Control Project, Carson and Santa Fe National Forests, New...

    Science.gov (United States)

    2013-10-30

    ... DEPARTMENT OF AGRICULTURE Forest Service Southwestern Region: Invasive Plant Control Project... Register (65 FR 78464) to prepare an environmental impact statement (EIS) for controlling invasive plants... update certain elements of the analysis and correct deficiencies identified in the 2005 Invasive Plant...

  14. 76 FR 36896 - Salmon-Challis National Forest, ID; Forestwide Invasive Plant Treatment Environmental Impact...

    Science.gov (United States)

    2011-06-23

    ... prepare an environmental impact statement. SUMMARY: Invasive plants have been identified as a major threat... Forest. Invasive plants create many adverse environmental effects, including, but not limited to... lands are also threatened by ``potential invaders,'' invasive plants that have not been found on the...

  15. Invasive plants transform the three-dimensional structure of rain forests

    Science.gov (United States)

    Gegory P. Asner; R. Flint Hughes; Peter M. Vitousek; David E. Knapp; Ty Kennedy-Bowdoin; Joseph Boardman; Roberta E. Martin; Michael Eastwood; Robert O. Green

    2008-01-01

    Biological invasions contribute to global environmental change, but the dynamics and consequences of most invasions are difficult to assess at regional scales. We deployed an airborne remote sensing system that mapped the location and impacts of five highly invasive plant species across 221,875 ha of Hawaiian ecosystems, identifying four distinct ways that these...

  16. Climate suitability and human influences combined explain the range expansion of an invasive horticultural plant

    Science.gov (United States)

    Carolyn M. Beans; Francis F. Kilkenny; Laura F. Galloway

    2012-01-01

    Ecological niche models are commonly used to identify regions at risk of species invasions. Relying on climate alone may limit a model's success when additional variables contribute to invasion. While a climate-based model may predict the future spread of an invasive plant, we hypothesized that a model that combined climate with human influences would most...

  17. MicroRNA-127-3p inhibits proliferation and invasion by targeting SETD8 in human osteosarcoma cells

    International Nuclear Information System (INIS)

    Zhang, Jun; Hou, Wengen; Chai, Mingxiang; Zhao, Hongxing; Jia, Jinling; Sun, Xiaohui; Zhao, Bin; Wang, Ran

    2016-01-01

    MicroRNAs (miRNAs) play an essential role in cancer development. Several studies have indicated that miRNAs mediate tumorigenesis processes, such as, inflammation, proliferation, apoptosis and invasion. In the present study, we focused on the influence of the miR-127-3p on the proliferation, migration and invasion of osteosarcoma (OS). MiR-127-3p was found at reduced levels in OS tissues and cell lines. Overexpression of miR-127-3p in the OS cell lines significantly inhibited the cell proliferation, migration and invasion; however, inhibition of miR-127-3p increased the proliferation, migration and invasion of OS in vitro. SETD8 was identified as a direct target of miR-127-3p, and SETD8 expression decreased post miR-127-3p overexpression, while SETD8 overexpression could reverse the potential influence of miR-127-3p on the migration and invasion of OS cells. MiR-127-3p is suggested to act mainly via the suppression of SETD8 expression. Overall, the results revealed that miR-127-3p acts as a tumor suppressor and that its down-regulation in cancer may contribute to OS progression and metastasis, suggesting that miR-127-3p could be a potential therapeutic target in the treatment of OS. - Highlights: • MiR-127-3p is decreased in osteosarcoma tissues and cell lines. • MiR-127-3p overexpression suppresses cell migration and invasion in MG63 and U2OS. • SETD8 overexpression abolishes the roles of miR-127-3p in osteosarcoma.

  18. Chronic invasive fungal granulomatous rhino-sinusitis: a case report ...

    African Journals Online (AJOL)

    Fungal Rhino-Sinusitis (FRS) is a relatively uncommon entity. The chronic invasive granulomatous form of FRS (FGRS) is a slowly progressive form of fungal infection characterized by chronic granulomatous process with a time course of longer than 12 weeks. The aim of this report is to draw the attention of colleagues to ...

  19. Perioperative management of nonmuscle-invasive bladder cancer

    NARCIS (Netherlands)

    Falke, J.; Witjes, J.A.

    2011-01-01

    PURPOSE OF REVIEW: The management of nonmuscle-invasive bladder cancer is a challenge. Despite current guidelines, the treatment is suboptimal as illustrated by the high risk of recurrence and progression. Transurethral resection plays a pivotal role in the management of bladder cancer, but the

  20. Does phosphorylation of cofilin affect the progression of human bladder cancer?

    International Nuclear Information System (INIS)

    Chung, Hong; Kim, Hong Sup; Kim, Bokyung; Jung, Seung-Hyo; Won, Kyung-Jong; Jiang, Xiaowen; Lee, Chang-Kwon; Lim, So Dug; Yang, Sang-Kuk; Song, Ki Hak

    2013-01-01

    We determined the differently expressed protein profiles and their functions in bladder cancer tissues with the aim of identifying possible target proteins and underlying molecular mechanisms for taking part in their progression. We examined the expression of proteins by proteomic analysis and western blot in normal urothelium, non-muscle-invasive bladder cancers (NMIBCs), and muscle-invasive bladder cancers (MIBCs). The function of cofilin was analyzed using T24 human bladder cancer cells. The expression levels of 12 proteins were altered between bladder cancers and normal bladder tissues. Of these proteins, 14-3-3σ was upregulated in both NMIBCs and MIBCs compared with controls. On the other hand, myosin regulatory light chain 2, galectin-1, lipid-binding AI, annexin V, transthyretin, CARD-inhibitor of NF-κB-activating ligand, and actin prepeptide were downregulated in cancer samples. Cofilin, an actin-depolymerizing factor, was prominent in both NMIBCs and MIBCs compared with normal bladder tissues. Furthermore, we confirmed that cofilin phosphorylation was more prominent in MIBCs than in NMIBCs using immunoblotting and immunohistochemcal analyses. Epidermal growth factor (EGF) increased the phosphorylation of cofilin and elevated the migration in T24 cells. Knockdown of cofilin expression with small interfering RNA attenuated the T24 cell migration in response to EGF. These results demonstrate that the increased expression and phosphorylation of cofilin might play a role in the occurrence and invasiveness of bladder cancer. We suspected that changes in cofilin expression may participate in the progression of the bladder cancer

  1. A conceptual framework for invasion in microbial communities

    KAUST Repository

    Kinnunen, Marta

    2016-05-03

    There is a growing interest in controlling-promoting or avoiding-the invasion of microbial communities by new community members. Resource availability and community structure have been reported as determinants of invasion success. However, most invasion studies do not adhere to a coherent and consistent terminology nor always include rigorous interpretations of the processes behind invasion. Therefore, we suggest that a consistent set of definitions and a rigorous conceptual framework are needed. We define invasion in a microbial community as the establishment of an alien microbial type in a resident community and argue how simple criteria to define aliens, residents, and alien establishment can be applied for a wide variety of communities. In addition, we suggest an adoption of the community ecology framework advanced by Vellend (2010) to clarify potential determinants of invasion. This framework identifies four fundamental processes that control community dynamics: dispersal, selection, drift and diversification. While selection has received ample attention in microbial community invasion research, the three other processes are often overlooked. Here, we elaborate on the relevance of all four processes and conclude that invasion experiments should be designed to elucidate the role of dispersal, drift and diversification, in order to obtain a complete picture of invasion as a community process.

  2. Resource competition in plant invasions: emerging patterns and research needs

    Science.gov (United States)

    Gioria, Margherita; Osborne, Bruce A.

    2014-01-01

    Invasions by alien plants provide a unique opportunity to examine competitive interactions among plants. While resource competition has long been regarded as a major mechanism responsible for successful invasions, given a well-known capacity for many invaders to become dominant and reduce plant diversity in the invaded communities, few studies have measured resource competition directly or have assessed its importance relative to that of other mechanisms, at different stages of an invasion process. Here, we review evidence comparing the competitive ability of invasive species vs. that of co-occurring native plants, along a range of environmental gradients, showing that many invasive species have a superior competitive ability over native species, although invasive congeners are not necessarily competitively superior over native congeners, nor are alien dominants are better competitors than native dominants. We discuss how the outcomes of competition depend on a number of factors, such as the heterogeneous distribution of resources, the stage of the invasion process, as well as phenotypic plasticity and evolutionary adaptation, which may result in increased or decreased competitive ability in both invasive and native species. Competitive advantages of invasive species over natives are often transient and only important at the early stages of an invasion process. It remains unclear how important resource competition is relative to other mechanisms (competition avoidance via phenological differences, niche differentiation in space associated with phylogenetic distance, recruitment and dispersal limitation, indirect competition, and allelopathy). Finally, we identify the conceptual and methodological issues characterizing competition studies in plant invasions, and we discuss future research needs, including examination of resource competition dynamics and the impact of global environmental change on competitive interactions between invasive and native species. PMID

  3. Overexpression of trefoil factor 3 (TFF3) contributes to the malignant progression in cervical cancer cells.

    Science.gov (United States)

    Yuan, Zhaohu; Chen, Dandan; Chen, Xiaojie; Yang, Huikuan; Wei, Yaming

    2017-01-01

    There remains a great need for effective therapies for cervical cancers, the majority of which are aggressive leaving patients with poor prognosis. Here, we identify a novel candidate therapeutic target, trefoil factor 3 (TFF3) which overexpressed in cervical cancer cells and was associated with reduced postoperative survival. Functional studies demonstrated that TFF3 overexpression promoted the proliferation and invasion of cervical cancer cells, and inhibited the apoptosis by inducing the mRNA changes in SiHa and Hela cell lines. Conversely, TFF3 silencing disrupted the proliferation and invasion of cervical cancer cells, and induced the apoptosis via Click-iT EdU test, flow cytometry analysis and two-dimensional Matrigel Transwell analysis. Western blot analysis showed that overexpression of TFF3 repressed E-cadherin (CDH1) expression to promote the invasion of cervical cancer cells. Furthermore, down-regulated CDH1 via overexpression of TFF3 was significantly up-regulated by virtue of inhibitor of p-STAT3. These results suggested that TFF3 stimulated the invasion of cervical cancer cells probably by activating the STAT3/CDH1 signaling pathway. Furthermore, overexpression of TFF3 decreased the sensitivity of cervical cancer cells to etoposide by increasing P-glycoprotein (P-gp) functional activity. Overall, our work provides a preclinical proof that TFF3 not only contributes to the malignant progression of cervical cancers and but also is a potential therapeutic target.

  4. Minimal Invasive Decompression for Lumbar Spinal Stenosis

    Directory of Open Access Journals (Sweden)

    Victor Popov

    2012-01-01

    Full Text Available Lumbar spinal stenosis is a common condition in elderly patients and may lead to progressive back and leg pain, muscular weakness, sensory disturbance, and/or problems with ambulation. Multiple studies suggest that surgical decompression is an effective therapy for patients with symptomatic lumbar stenosis. Although traditional lumbar decompression is a time-honored procedure, minimally invasive procedures are now available which can achieve the goals of decompression with less bleeding, smaller incisions, and quicker patient recovery. This paper will review the technique of performing ipsilateral and bilateral decompressions using a tubular retractor system and microscope.

  5. Sonomammographic characteristics of invasive lobular carcinoma

    Directory of Open Access Journals (Sweden)

    El-Damshety O

    2012-07-01

    Full Text Available Osama R Kombar,1,3 Dalia M Fahmy,1 Mary V Brown,3 Omar Farouk,2 Osama El-Damshety21Diagnostic Radiology Department, 2Surgical Oncology Department, Oncology Center, Mansoura University, Mansoura, Egypt; 3Diagnostic Radiology Department, Al-Amiri Hospital, Safat, KuwaitObjective: The objective of our study was to identify characteristic features of invasive lobular carcinoma on mammography and ultrasound examinationsMaterials and methods: This is a retrospective multicenter study of women with biopsy-proven invasive lobular carcinoma. All patients had undergone diagnostic sonomammography. The imaging findings were identified by experienced breast imagers. Final surgical pathology results were used as the reference standard.Results: Thirty-two women ranging in age from 42 to 63 years old (mean age, 53 years, All had biopsy-proven invasive lobular carcinomas. Common features on mammogram included dense mass followed by architectural distortion; three cases showed breast asymmetry and one case was reported as normal. On ultrasound, common features included solid mass with spiculated margins, posterior shadowing, and perpendicular to the skin.Conclusion: Although no specific features could be linked to invasive lobular carcinoma, care should be directed to subtle signs such as architectural distortion and breast asymmetry in order not to miss any lesions. The combination of mammographic and sonographic helps to decrease the relatively high false negative diagnosis of this type of breast cancer.Keywords: mammography, ultrasound, cancer, breast

  6. Progress in the Diagnosis and Classification of Pituitary Adenomas

    Science.gov (United States)

    Syro, Luis V.; Rotondo, Fabio; Ramirez, Alex; Di Ieva, Antonio; Sav, Murat Aydin; Restrepo, Lina M.; Serna, Carlos A.; Kovacs, Kalman

    2015-01-01

    Pituitary adenomas are common neoplasms. Their classification is based upon size, invasion of adjacent structures, sporadic or familial cases, biochemical activity, clinical manifestations, morphological characteristics, response to treatment and recurrence. Although they are considered benign tumors, some of them are difficult to treat due to their tendency to recur despite standardized treatment. Functional tumors present other challenges for normalizing their biochemical activity. Novel approaches for early diagnosis, as well as different perspectives on classification, may help to identify subgroups of patients with similar characteristics, creating opportunities to match each patient with the best personalized treatment option. In this paper, we present the progress in the diagnosis and classification of different subgroups of patients with pituitary tumors that may be managed with specific considerations according to their tumor subtype. PMID:26124750

  7. Minimally Invasive Abdominal Surgery

    OpenAIRE

    Richardson, William S.; Carter, Kristine M.; Fuhrman, George M.; Bolton, John S.; Bowen, John C.

    2000-01-01

    In the last decade, laparoscopy has been the most innovative surgical movement in general surgery. Minimally invasive surgery performed through a few small incisions, laparoscopy is the standard of care for the treatment of gallbladder disease and the gold standard for the treatment of reflux disease. The indications for a laparoscopic approach to abdominal disease continue to increase, and many diseases may be treated with laparoscopic techniques. At Ochsner, laparoscopic techniques have dem...

  8. Towards Effective Non-Invasive Brain-Computer Interfaces Dedicated to Gait Rehabilitation Systems

    Directory of Open Access Journals (Sweden)

    Thierry Castermans

    2013-12-01

    Full Text Available In the last few years, significant progress has been made in the field of walk rehabilitation. Motor cortex signals in bipedal monkeys have been interpreted to predict walk kinematics. Epidural electrical stimulation in rats and in one young paraplegic has been realized to partially restore motor control after spinal cord injury. However, these experimental trials are far from being applicable to all patients suffering from motor impairments. Therefore, it is thought that more simple rehabilitation systems are desirable in the meanwhile. The goal of this review is to describe and summarize the progress made in the development of non-invasive brain-computer interfaces dedicated to motor rehabilitation systems. In the first part, the main principles of human locomotion control are presented. The paper then focuses on the mechanisms of supra-spinal centers active during gait, including results from electroencephalography, functional brain imaging technologies [near-infrared spectroscopy (NIRS, functional magnetic resonance imaging (fMRI, positron-emission tomography (PET, single-photon emission-computed tomography (SPECT] and invasive studies. The first brain-computer interface (BCI applications to gait rehabilitation are then presented, with a discussion about the different strategies developed in the field. The challenges to raise for future systems are identified and discussed. Finally, we present some proposals to address these challenges, in order to contribute to the improvement of BCI for gait rehabilitation.

  9. Plant invasions: Merging the concepts of species invasiveness and community invasibility

    Czech Academy of Sciences Publication Activity Database

    Richardson, D. M.; Pyšek, Petr

    2006-01-01

    Roč. 30, č. 3 (2006), s. 409-431 ISSN 0309-1333 Institutional research plan: CEZ:AV0Z60050516 Keywords : plant invasions * species invasiveness * community invasibility Subject RIV: EF - Botanics Impact factor: 1.278, year: 2006

  10. Secondary invasions of noxious weeds associated with control of invasive Tamarix are frequent, idiosyncratic and persistent

    Science.gov (United States)

    González, Eduardo; Sher, Anna A.; Anderson, Robert M.; Bay, Robin F.; Bean, Daniel W.; Bissonnete, Gabriel J.; Cooper, David J.; Dohrenwend, Kara; Eichhorst, Kim D.; El Waer, Hisham; Kennard, Deborah K.; Harms-Weissinger, Rebecca; Henry, Annie L.; Makarick, Lori J.; Ostoja, Steven M.; Reynolds, Lindsay V.; Robinson, W. Wright; Shafroth, Patrick B.; Tabacchi, Erich

    2017-01-01

    Control of invasive species within ecosystems may induce secondary invasions of non-target invaders replacing the first alien. We used four plant species listed as noxious by local authorities in riparian systems to discern whether 1) the severity of these secondary invasions was related to the control method applied to the first alien; and 2) which species that were secondary invaders persisted over time. In a collaborative study by 16 research institutions, we monitored plant species composition following control of non-native Tamarix trees along southwestern U.S. rivers using defoliation by an introduced biocontrol beetle, and three physical removal methods: mechanical using saws, heavy machinery, and burning in 244 treated and 79 untreated sites across six U.S. states. Physical removal favored secondary invasions immediately after Tamarix removal (0–3 yrs.), while in the biocontrol treatment, secondary invasions manifested later (> 5 yrs.). Within this general trend, the response of weeds to control was idiosyncratic; dependent on treatment type and invader. Two annual tumbleweeds that only reproduce by seed (Bassia scoparia and Salsola tragus) peaked immediately after physical Tamarix removal and persisted over time, even after herbicide application. Acroptilon repens, a perennial forb that vigorously reproduces by rhizomes, and Bromus tectorum, a very frequent annual grass before removal that only reproduces by seed, were most successful at biocontrol sites, and progressively spread as the canopy layer opened. These results demonstrate that strategies to control Tamarix affect secondary invasions differently among species and that time since disturbance is an important, generally overlooked, factor affecting response.

  11. Invasive plant species in the West Indies: geographical, ecological, and floristic insights.

    Science.gov (United States)

    Rojas-Sandoval, Julissa; Tremblay, Raymond L; Acevedo-Rodríguez, Pedro; Díaz-Soltero, Hilda

    2017-07-01

    The level of invasion (number or proportion of invasive species) in a given area depends on features of the invaded community, propagule pressure, and climate. In this study, we assess the invasive flora of nine islands in the West Indies to identify invasion patterns and evaluate whether invasive species diversity is related to geographical, ecological, and socioeconomic factors. We compiled a database of invasive plant species including information on their taxonomy, origin, pathways of introduction, habitats, and life history. This database was used to evaluate the similarity of invasive floras between islands and to identify invasion patterns at regional (West Indies) and local (island) scales. We found a total of 516 alien plant species that are invasive on at least one of the nine islands studied, with between 24 to 306 invasive species per island. The invasive flora on these islands includes a wide range of taxonomic groups, life forms, and habitats. We detected low similarity in invasive species diversity between islands, with most invasive species (>60%) occurring on a single island and 6% occurring on at least five islands. To assess the importance of different models in predicting patterns of invasive species diversity among islands, we used generalized linear models. Our analyses revealed that invasive species diversity was well predicted by a combination of island area and economic development (gross domestic product per capita and kilometers of paved roadways). Our results provide strong evidence for the roles of geographical, ecological, and socioeconomic factors in determining the distribution and spread of invasive species on these islands. Anthropogenic disturbance and economic development seem to be the major drivers facilitating the spread and predominance of invasive species over native species.

  12. Direct-Conversion Molecular Breast Imaging of Invasive Breast Cancer: Imaging Features, Extent of Invasive Disease, and Comparison Between Invasive Ductal and Lobular Histology.

    Science.gov (United States)

    Conners, Amy Lynn; Jones, Katie N; Hruska, Carrie B; Geske, Jennifer R; Boughey, Judy C; Rhodes, Deborah J

    2015-09-01

    The purposes of this study were to compare the tumor appearance of invasive breast cancer on direct-conversion molecular breast imaging using a standardized lexicon and to determine how often direct-conversion molecular breast imaging identifies all known invasive tumor foci in the breast, and whether this differs for invasive ductal versus lobular histologic profiles. Patients with prior invasive breast cancer and concurrent direct-conversion molecular breast imaging examinations were retrospectively reviewed. Blinded review of direct-conversion molecular breast imaging examinations was performed by one of two radiologists, according to a validated lexicon. Direct-conversion molecular breast imaging findings were matched with lesions described on the pathology report to exclude benign reasons for direct-conversion molecular breast imaging findings and to document direct-conversion molecular breast imaging-occult tumor foci. Associations between direct-conversion molecular breast imaging findings and tumor histologic profiles were examined using chi-square tests. In 286 patients, 390 invasive tumor foci were present in 294 breasts. A corresponding direct-conversion molecular breast imaging finding was present for 341 of 390 (87%) tumor foci described on the pathology report. Invasive ductal carcinoma (IDC) tumor foci were more likely to be a mass (40% IDC vs 15% invasive lobular carcinoma [ILC]; p invasive disease in 79.8% of cases and was more likely to do so for IDC than for ILC (86.1% vs 56.7%; p invasive foci in 249 of 286 (87%) patients. Direct-conversion molecular breast imaging features of invasive cancer, including lesion type and intensity, differ by histologic subtype. Direct-conversion molecular breast imaging is less likely to show all foci of ILC compared with IDC.

  13. Progression og underviserkompetencer

    Directory of Open Access Journals (Sweden)

    Lene Tortzen Bager

    2014-03-01

    entrepreneurship. The study uses categories such as didactics, working processes in academic courses or courses at university as key themes. Participating teachers’ descriptions of their concepts of entrepreneurship in their teaching practices are used to chart their progress. This material provides an insight into the teachers’ reflections on their development processes, challenges and different modes of teacher authority related to entrepreneurship teaching in universities. Together, the gathered data contribute to discussions on student teacher development by identifying the importance of the teachers’ motivation as a precondition for professional and educational development. 

  14. Progression og underviserkompetencer

    Directory of Open Access Journals (Sweden)

    Lene Tortzen Bager

    2014-03-01

    entrepreneurship. The study uses categories such as didactics, working processes in academic courses or courses at university as key themes. Participating teachers’ descriptions of their concepts of entrepreneurship in their teaching practices are used to chart their progress. This material provides an insight into the teachers’ reflections on their development processes, challenges and different modes of teacher authority related to entrepreneurship teaching in universities. Together, the gathered data contribute to discussions on student teacher development by identifying the importance of the teachers’ motivation as a precondition for professional and educational development.

  15. Placenta-specific protein 1 promotes cell proliferation and invasion in non-small cell lung cancer

    Science.gov (United States)

    Yang, Li; Zha, Tian-Qi; He, Xiang; Chen, Liang; Zhu, Quan; Wu, Wei-Bing; Nie, Feng-Qi; Wang, Qian; Zang, Chong-Shuang; Zhang, Mei-Ling; He, Jing; Li, Wei; Jiang, Wen; Lu, Kai-Hua

    2018-01-01

    Pulmonary carcinoma-associated proteins have emerged as crucial players in governing fundamental biological processes such as cell proliferation, apoptosis and metastasis in human cancers. Placenta-specific protein 1 (PLAC1) is a cancer-related protein, which is activated and upregulated in a variety of malignant tissues, including prostate cancer, gastric adenocarcinoma, colorectal, epithelial ovarian and breast cancer. However, its biological role and clinical significance in non-small cell lung cancer (NSCLC) development and progression are still unknown. In the present study, we found that PLAC1 was significantly upregulated in NSCLC tissues, and its expression level was associated with advanced pathological stage and it was also correlated with shorter progression-free survival of lung cancer patients. Furthermore, knockdown of PLAC1 expression by siRNA inhibited cell proliferation, induced apoptosis and impaired invasive ability in NSCLC cells partly via regulation of epithelial-mesenchymal transition (EMT)-related protein expression. Our findings present that increased PLAC1 could be identified as a negative prognostic biomarker in NSCLC and regulate cell proliferation and invasion. Thus, we conclusively demonstrated that PLAC1 plays a key role in NSCLC development and progression, which may provide novel insights on the function of tumor-related gene-driven tumorigenesis. PMID:29138842

  16. An assessment of the effectiveness of a large, national-scale invasive alien plant control strategy in South Africa

    CSIR Research Space (South Africa)

    Van Wilgen, BW

    2012-04-01

    Full Text Available extent of invasive species control operations, assessments of the effectiveness of biological control, and smaller-scale studies. The 19 most important invasive taxa, mainly trees, in terrestrial biomes were identified. The effectiveness of control...

  17. Expression of Axl in Lung Adenocarcinoma and Correlation with Tumor Progression

    Directory of Open Access Journals (Sweden)

    Yi-Shing Shinh

    2005-12-01

    Full Text Available We used the Transwell system to select highly invasive cell lines from minimally invasive parent cells, and we compared gene expression in paired cell lines with high and low invasive potentials. Axl was relatively overexpressed in the highly invasive cell lines when compared with their minimally invasive counterparts. However, there is only limited information about the role of Axl in cancer invasion. The biologic function of Axl in tumor invasion was investigated by overexpression of full-length Axl in minimally invasive cells and by siRNA knockdown of Axl expression in highly invasive cells. Overexpression of Axl in minimally invasive cells increased their invasiveness. siRNA reduced cell invasiveness as Axl was downregulated in highly invasive cells. We further investigated the protein expression of Axl by immunohistochemistry and its correlation with clinicopathologic features. Data from a study of 58 patient specimens showed that Axl immunoreactivity was statistically significant with respect to lymph node status (P < .0001 and the patient's clinical stage (P < .0001. Our results demonstrate that Axl protein kinase seems to play an important role in the invasion and progression of lung cancer.

  18. Federal Facility Agreement progress report

    Energy Technology Data Exchange (ETDEWEB)

    1993-10-01

    The (SRS) Federal Facility Agreement (FFA) was made effective by the US. Environmental Protection Agency Region IV (EPA) on August 16, 1993. To meet the reporting requirements in Section XXV of the Agreement, the FFA Progress Report was developed. The FFA Progress Report is the first of a series of quarterly progress reports to be prepared by the SRS. As such this report describes the information and action taken to September 30, 1993 on the SRS units identified for investigation and remediation in the Agreement. This includes; rubble pits, runoff basins, retention basin, seepage basin, burning pits, H-Area Tank 16, and spill areas.

  19. Federal Facility Agreement progress report

    International Nuclear Information System (INIS)

    1993-10-01

    The (SRS) Federal Facility Agreement (FFA) was made effective by the US. Environmental Protection Agency Region IV (EPA) on August 16, 1993. To meet the reporting requirements in Section XXV of the Agreement, the FFA Progress Report was developed. The FFA Progress Report is the first of a series of quarterly progress reports to be prepared by the SRS. As such this report describes the information and action taken to September 30, 1993 on the SRS units identified for investigation and remediation in the Agreement. This includes; rubble pits, runoff basins, retention basin, seepage basin, burning pits, H-Area Tank 16, and spill areas

  20. MYCN and HDAC5 transcriptionally repress CD9 to trigger invasion and metastasis in neuroblastoma

    Science.gov (United States)

    Fabian, Johannes; Opitz, Desirée; Althoff, Kristina; Lodrini, Marco; Hero, Barbara; Volland, Ruth; Beckers, Anneleen; de Preter, Katleen; Decock, Anneleen; Patil, Nitin; Abba, Mohammed; Kopp-Schneider, Annette; Astrahantseff, Kathy; Wünschel, Jasmin; Pfeil, Sebastian; Ercu, Maria; Künkele, Annette; Hu, Jamie; Thole, Theresa; Schweizer, Leonille; Mechtersheimer, Gunhild; Carter, Daniel; Cheung, Belamy B.; Popanda, Odilia; von Deimling, Andreas; Koster, Jan; Versteeg, Rogier; Schwab, Manfred; Marshall, Glenn M.; Speleman, Frank; Erb, Ulrike; Zoeller, Margot; Allgayer, Heike; Simon, Thorsten; Fischer, Matthias; Kulozik, Andreas E.; Eggert, Angelika; Witt, Olaf; Schulte, Johannes H.; Deubzer, Hedwig E.

    2016-01-01

    The systemic and resistant nature of metastatic neuroblastoma renders it largely incurable with current multimodal treatment. Clinical progression stems mainly from the increasing burden of metastatic colonization. Therapeutically inhibiting the migration-invasion-metastasis cascade would be of great benefit, but the mechanisms driving this cycle are as yet poorly understood. In-depth transcriptome analyses and ChIP-qPCR identified the cell surface glycoprotein, CD9, as a major downstream player and direct target of the recently described GRHL1 tumor suppressor. CD9 is known to block or facilitate cancer cell motility and metastasis dependent upon entity. High-level CD9 expression in primary neuroblastomas correlated with patient survival and established markers for favorable disease. Low-level CD9 expression was an independent risk factor for adverse outcome. MYCN and HDAC5 colocalized to the CD9 promoter and repressed transcription. CD9 expression diminished with progressive tumor development in the TH-MYCN transgenic mouse model for neuroblastoma, and CD9 expression in neuroblastic tumors was far below that in ganglia from wildtype mice. Primary neuroblastomas lacking MYCN amplifications displayed differential CD9 promoter methylation in methyl-CpG-binding domain sequencing analyses, and high-level methylation was associated with advanced stage disease, supporting epigenetic regulation. Inducing CD9 expression in a SH-EP cell model inhibited migration and invasion in Boyden chamber assays. Enforced CD9 expression in neuroblastoma cells transplanted onto chicken chorioallantoic membranes strongly reduced metastasis to embryonic bone marrow. Combined treatment of neuroblastoma cells with HDAC/DNA methyltransferase inhibitors synergistically induced CD9 expression despite hypoxic, metabolic or cytotoxic stress. Our results show CD9 is a critical and indirectly druggable suppressor of the invasion-metastasis cycle in neuroblastoma. PMID:27572323

  1. Sonomammographic characteristics of invasive lobular carcinoma

    OpenAIRE

    Fahmy, Dalia Monir; Kombar,; Farouk,Omar; El-damshety,; Brown,

    2012-01-01

    Osama R Kombar,1,3 Dalia M Fahmy,1 Mary V Brown,3 Omar Farouk,2 Osama El-Damshety21Diagnostic Radiology Department, 2Surgical Oncology Department, Oncology Center, Mansoura University, Mansoura, Egypt; 3Diagnostic Radiology Department, Al-Amiri Hospital, Safat, KuwaitObjective: The objective of our study was to identify characteristic features of invasive lobular carcinoma on mammography and ultrasound examinationsMaterials and methods: This is a retrospective multicenter study of women with ...

  2. The assessment of angiogenesis and fibroblastic stromagenesis in hyperplastic and pre-invasive breast lesions

    International Nuclear Information System (INIS)

    Pavlakis, Kitty; Messini, Irene; Vrekoussis, Thomas; Yiannou, Petros; Keramopoullos, Dimitrios; Louvrou, Niki; Liakakos, Theodoros; Stathopoulos, Efstathios N

    2008-01-01

    To investigate the changes of the neoplastic microenvironment during the different morphological alterations of hyperplastic and pre-invasive breast lesions. 78 in situ ductal carcinomas of all degrees of differentiation, 22 atypical ductal hyperplasias, 25 in situ lobular carcinomas, 18 atypical lobular hyperplasias, 32 ductal epithelial hyperplasias of usual type and 8 flat atypias were immunohistochemically investigated for the expression of vascular endothelial growth factor (VEGF), smooth muscle actin (SMA) and CD34, while microvessel density (MVD) was counted using the anti-CD31 antibody. VEGF expression was strongly correlated with MVD in all hyperplastic and pre-invasive breast lesions (p < 0.05). Stromagenesis, as characterized by an increase in SMA and a decrease in CD34 positive myofibroblasts was observed mostly around ducts harboring high grade in situ carcinoma and to a lesser extent around moderately differentiated DCIS. In these two groups of in situ carcinomas, a positive correlation between MVD and SMA (p < 0.05) was observed. On the contrary, CD34 was found to be inversely related to MVD (p < 0.05). No statistically significant changes of the stromal fibroblasts were observed in low grade DCIS neither in any of the other lesions under investigation as compared to normal mammary intra- and interlobular stroma. Angiogenesis is observed before any significant fibroblastic stromagenesis in pre-invasive breast lesions. A composite phenotype characterized by VEGF positive epithelial cells and SMA positive/CD34 negative stromal cells, is identified mostly in intermediate and high grade DCIS. These findings might imply for new therapeutic strategies using both anti-angiogenic factors and factors selectively targeting tumor stroma in order to prevent the progression of DCIS to invasive carcinoma

  3. TR4 nuclear receptor suppresses HCC cell invasion via downregulating the EphA2 expression.

    Science.gov (United States)

    Jin, Ren'an; Lin, Hui; Li, Gonghui; Xu, Junjie; Shi, Liang; Chang, Chawnshang; Cai, Xiujun

    2018-02-15

    Early studies indicated that testicular nuclear receptor 4 (TR 4 ) could function as a suppressor in the transcriptional regulation of the HBV core gene expression, which might then influence the development of hepatocellular carcinoma (HCC). The direct linkage between TR 4 and HCC progression, however, remained unclear. Here, via a human clinical sample survey, we found that 13 of the 18 HCC patients studied had lower TR 4 expression in metastatic lesions than in matched primary HCC lesions, suggesting that TR 4 may play a negative role in HCC metastasis. Results from in vitro cell migration/invasion studied confirmed that TR 4 could suppress HCC cell migration/invasion. Mechanism dissection revealed that TR 4 might function through downregulating ephrin type-A receptor 2 (EphA2) expression at the transcriptional level via direct binding to the TR 4 REs located on the 5' promoter of EphA2 to suppress HCC cell migration/invasion. Targeting the EphA2 via EphA2-siRNA partially reversed the enhanced HCC cell migration/invasion with confirmed TR 4 knockdown. Notably, results from preclinical studies using in vivo mouse model with orthotopic xenograft of HCC LM3 cells also confirmed the in vitro findings. Taking these findings together, preclinical studies using multiple in vitro HCC cell lines and an in vivo mouse model all led to the conclusion that TR 4 may function as a suppressor of HCC metastasis and that targeting this newly identified TR 4 -EphA2 signaling may improve our ability to suppress HCC metastasis.

  4. Minimally Invasive Parathyroidectomy

    Directory of Open Access Journals (Sweden)

    Lee F. Starker

    2011-01-01

    Full Text Available Minimally invasive parathyroidectomy (MIP is an operative approach for the treatment of primary hyperparathyroidism (pHPT. Currently, routine use of improved preoperative localization studies, cervical block anesthesia in the conscious patient, and intraoperative parathyroid hormone analyses aid in guiding surgical therapy. MIP requires less surgical dissection causing decreased trauma to tissues, can be performed safely in the ambulatory setting, and is at least as effective as standard cervical exploration. This paper reviews advances in preoperative localization, anesthetic techniques, and intraoperative management of patients undergoing MIP for the treatment of pHPT.

  5. Severe invasive listeriosis--case report.

    Science.gov (United States)

    Teodor, Andra; Teodor, D; Miftode, Egidia; Prisăcaru, D; Leca, Daniela; Petrovici, Cristina; Dorneanu, Olivia; Dorobăt, Carmen-Mihaela

    2012-01-01

    Listeriosis is a rare food borne infection which, in the invasive form, presents as bloodstream infection, central nervous system infection, materno-fetal infection, or focal infection. Certain immunosuppressive conditions have been identified as risk factors for severe invasive disease. The invasive forms of listeriosis are associated with a high case fatality rate. We present the case of a 62-year-old male with an unremarkable medical history admitted to the Iasi Infectious Diseases Hospital for fever. headache, ataxia, and diplopia. Physical examination revealed high temperature, confusion, relative bradycardia, and signs of meningeal irritation. Laboratory test showed leukocyt osis with neutrophilia. pathological CSF findings (high WBC count with predominance of neutrophils, low glucose and high protein levels), increased liver enzymes (ALAT, ASAT, AP, gammaGT), and important renal impairment (normal levels at presentation). No abnormalities at chest x-ray, cranial CT and abdominal ultrasound. CSF and blood cultures were positive for Listeria monocytogenes. Under antibiotics (ampicillin and ciprofloxacin), the course was marked by respiratory failure requiring mechanical ventilation, coma, hypotension, tachycardia. and death 12 days after admission. The particularity of this case consists in the association of the two classical forms of invasive listeriosis, meningitis and bacteriemia, with a focal infection. acute hepatitis, and a course marked by multiple organ dysfunction syndromes and exitus in a previously apparently healthy individual.

  6. Intratumoral oxygen gradients mediate sarcoma cell invasion

    Science.gov (United States)

    Lewis, Daniel M.; Park, Kyung Min; Tang, Vitor; Xu, Yu; Pak, Koreana; Eisinger-Mathason, T. S. Karin; Simon, M. Celeste; Gerecht, Sharon

    2016-01-01

    Hypoxia is a critical factor in the progression and metastasis of many cancers, including soft tissue sarcomas. Frequently, oxygen (O2) gradients develop in tumors as they grow beyond their vascular supply, leading to heterogeneous areas of O2 depletion. Here, we report the impact of hypoxic O2 gradients on sarcoma cell invasion and migration. O2 gradient measurements showed that large sarcoma mouse tumors (>300 mm3) contain a severely hypoxic core [≤0.1% partial pressure of O2 (pO2)] whereas smaller tumors possessed hypoxic gradients throughout the tumor mass (0.1–6% pO2). To analyze tumor invasion, we used O2-controllable hydrogels to recreate the physiopathological O2 levels in vitro. Small tumor grafts encapsulated in the hydrogels revealed increased invasion that was both faster and extended over a longer distance in the hypoxic hydrogels compared with nonhypoxic hydrogels. To model the effect of the O2 gradient accurately, we examined individual sarcoma cells embedded in the O2-controllable hydrogel. We observed that hypoxic gradients guide sarcoma cell motility and matrix remodeling through hypoxia-inducible factor-1α (HIF-1α) activation. We further found that in the hypoxic gradient, individual cells migrate more quickly, across longer distances, and in the direction of increasing O2 tension. Treatment with minoxidil, an inhibitor of hypoxia-induced sarcoma metastasis, abrogated cell migration and matrix remodeling in the hypoxic gradient. Overall, we show that O2 acts as a 3D physicotactic agent during sarcoma tumor invasion and propose the O2-controllable hydrogels as a predictive system to study early stages of the metastatic process and therapeutic targets. PMID:27486245

  7. Placing invasive species management in a spatiotemporal context.

    Science.gov (United States)

    Baker, Christopher M; Bode, Michael

    2016-04-01

    Invasive species are a worldwide issue, both ecologically and economically. A large body of work focuses on various aspects of invasive species control, including how to allocate control efforts to eradicate an invasive population as cost effectively as possible: There are a diverse range of invasive species management problems, and past mathematical analyses generally focus on isolated examples, making it hard to identify and understand parallels between the different contexts. In this study, we use a single spatiotemporal model to tackle the problem of allocating control effort for invasive species when suppressing an island invasive species, and for long-term spatial suppression projects. Using feral cat suppression as an illustrative example, we identify the optimal resource allocation for island and mainland suppression projects. Our results demonstrate how using a single model to solve different problems reveals similar characteristics of the solutions in different scenarios. As well as illustrating the insights offered by linking problems through a spatiotemporal model, we also derive novel and practically applicable results for our case studies. For temporal suppression projects on islands, we find that lengthy projects are more cost effective and that rapid control projects are only economically cost effective when population growth rates are high or diminishing returns on control effort are low. When suppressing invasive species around conservation assets (e.g., national parks or exclusion fences), we find that the size of buffer zones should depend on the ratio of the species growth and spread rate.

  8. Up-regulation of METCAM/MUC18 promotes motility, invasion, and tumorigenesis of human breast cancer cells

    Directory of Open Access Journals (Sweden)

    Cai Shao-xi

    2011-03-01

    Full Text Available Abstract Background Conflicting research has identified METCAM/MUC18, an integral membrane cell adhesion molecule (CAM in the Ig-like gene super-family, as both a tumor promoter and a tumor suppressor in the development of breast cancer. To resolve this, we have re-investigated the role of this CAM in the progression of human breast cancer cells. Methods Three breast cancer cell lines were used for the tests: one luminal-like breast cancer cell line, MCF7, which did not express any METCAM/MUC18, and two basal-like breast cancer cell lines, MDA-MB-231 and MDA-MB-468, which expressed moderate levels of the protein. MCF7 cells were transfected with the human METCAM/MUC18 cDNA to obtain G418-resistant clones which expressed the protein and were used for testing effects of human METCAM/MUC18 expression on in vitro motility and invasiveness, and in vitro and in vivo tumorigenesis. Both MDA-MB-231 and MDA-MB-468 cells already expressed METCAM/MUC18. They were directly used for in vitro tests in the presence and absence of an anti-METCAM/MUC18 antibody. Results In MCF7 cells, enforced METCAM/MUC18 expression increased in vitro motility, invasiveness, anchorage-independent colony formation (in vitro tumorigenesis, and in vivo tumorigenesis. In both MDA-MB-231 and MDA-MB-468 cells, the anti-METCAM/MUC18 antibody inhibited both motility and invasiveness. Though both MDA-MB-231 and MDA-MB-468 cells established a disorganized growth in 3D basement membrane culture assay, the introduction of the anti-METCAM/MUC18 antibody completely destroyed their growth in the 3D culture. Conclusion These findings support the notion that human METCAM/MUC18 expression promotes the progression of human breast cancer cells by increasing their motility, invasiveness and tumorigenesis.

  9. A comparison of non-invasive versus invasive methods of ...

    African Journals Online (AJOL)

    Puneet Khanna

    for Hb estimation from the laboratory [total haemoglobin mass (tHb)] and arterial blood gas (ABG) machine (aHb), using ... A comparison of non-invasive versus invasive methods of haemoglobin estimation in patients undergoing intracranial surgery. 161 .... making decisions for blood transfusions based on these results.

  10. Invasive v. non-invasive blood pressure measurements the ...

    African Journals Online (AJOL)

    A reasonable correlation exists between invasive and noninvasive methods of measuring systemic blood pressure. However, there are frequent individual differences between these methods and these variations have often caused the validity of the non-invasive measurement to be questioned. The hypothesis that certain ...

  11. The effect of blood pressure on non-invasive fractional flow reserve derived from coronary computed tomography angiography

    Energy Technology Data Exchange (ETDEWEB)

    Kurata, Akira [Ehime University Graduate School of Medicine, Department of Radiology, Toon, Ehime (Japan); Erasmus University Medical Center, Department of Radiology, Rotterdam (Netherlands); Coenen, Adriaan; Lubbers, Marisa M.; Nieman, Koen [Erasmus University Medical Center, Department of Radiology, Rotterdam (Netherlands); Erasmus University Medical Center, Departmenet of Cardiology, Rotterdam (Netherlands); Kido, Teruhito; Mochizuki, Teruhito [Ehime University Graduate School of Medicine, Department of Radiology, Toon, Ehime (Japan); Kido, Tomoyuki [Matsuyama Saiseikai Hospital, Department of Radiology, Matsuyama, Ehime (Japan); Yamashita, Natsumi [Clinical Research Center, National Hospital Organization Shikoku Cancer Center, Division of Clinical Biostatistics, Section of Cancer Prevention and Epidemiology, Matsuyama, Ehime (Japan); Watanabe, Kouki [Matsuyama Saiseikai Hospital, Department of Cardiology, Matsuyama, Ehime (Japan); Krestin, Gabriel P. [Erasmus University Medical Center, Department of Radiology, Rotterdam (Netherlands)

    2017-04-15

    The aim of this study is to assess the effect of blood pressure (BP) on coronary computed tomography angiography (CTA) derived computational fractional flow reserve (CTA-FFR). Twenty-one patients who underwent coronary CTA and invasive FFR were retrospectively identified. Ischemia was defined as invasive FFR ≤0.80. Using a work-in-progress computational fluid dynamics algorithm, CTA-FFR was computed with BP measured before CTA, and simulated BPs of 60/50, 90/60, 110/70, 130/80, 150/90, and 180/100 mmHg respectively. Correlation between CTA-FFR and invasive FFR was assessed using Pearson test. The repeated measuring test was used for multiple comparisons of CTA-FFR values by simulated BP inputs. Twenty-nine vessels (14 with invasive FFR ≤0.80) were assessed. The average CTA-FFR for measured BP (134 ± 20/73 ± 12 mmHg) was 0.77 ± 0.12. Correlation between CTA-FFR by measured BP and invasive FFR was good (r = 0.735, P < 0.001). For simulated BPs of 60/50, 90/60, 110/70, 130/80, 150/90, and 180/100 mmHg, the CTA-FFR increased: 0.69 ± 0.13, 0.73 ± 0.12, 0.75 ± 0.12, 0.77 ± 0.11, 0.79 ± 0.11, and 0.81 ± 0.10 respectively (P < 0.05). Measurement of the BP just before CTA is preferred for accurate CTA-FFR simulation. BP variations in the common range slightly affect CTA-FFR. However, inaccurate BP assumptions differing from the patient-specific BP could cause misinterpretation of borderline significant lesions. (orig.)

  12. The effect of blood pressure on non-invasive fractional flow reserve derived from coronary computed tomography angiography

    International Nuclear Information System (INIS)

    Kurata, Akira; Coenen, Adriaan; Lubbers, Marisa M.; Nieman, Koen; Kido, Teruhito; Mochizuki, Teruhito; Kido, Tomoyuki; Yamashita, Natsumi; Watanabe, Kouki; Krestin, Gabriel P.

    2017-01-01

    The aim of this study is to assess the effect of blood pressure (BP) on coronary computed tomography angiography (CTA) derived computational fractional flow reserve (CTA-FFR). Twenty-one patients who underwent coronary CTA and invasive FFR were retrospectively identified. Ischemia was defined as invasive FFR ≤0.80. Using a work-in-progress computational fluid dynamics algorithm, CTA-FFR was computed with BP measured before CTA, and simulated BPs of 60/50, 90/60, 110/70, 130/80, 150/90, and 180/100 mmHg respectively. Correlation between CTA-FFR and invasive FFR was assessed using Pearson test. The repeated measuring test was used for multiple comparisons of CTA-FFR values by simulated BP inputs. Twenty-nine vessels (14 with invasive FFR ≤0.80) were assessed. The average CTA-FFR for measured BP (134 ± 20/73 ± 12 mmHg) was 0.77 ± 0.12. Correlation between CTA-FFR by measured BP and invasive FFR was good (r = 0.735, P < 0.001). For simulated BPs of 60/50, 90/60, 110/70, 130/80, 150/90, and 180/100 mmHg, the CTA-FFR increased: 0.69 ± 0.13, 0.73 ± 0.12, 0.75 ± 0.12, 0.77 ± 0.11, 0.79 ± 0.11, and 0.81 ± 0.10 respectively (P < 0.05). Measurement of the BP just before CTA is preferred for accurate CTA-FFR simulation. BP variations in the common range slightly affect CTA-FFR. However, inaccurate BP assumptions differing from the patient-specific BP could cause misinterpretation of borderline significant lesions. (orig.)

  13. Using Copy Number Alterations to Identify New Therapeutic Targets for Bladder Carcinoma

    Directory of Open Access Journals (Sweden)

    Donatella Conconi

    2016-02-01

    Full Text Available Bladder cancer represents the ninth most widespread malignancy throughout the world. It is characterized by the presence of two different clinical and prognostic subtypes: non-muscle-invasive bladder cancers (NMIBCs and muscle-invasive bladder cancers (MIBCs. MIBCs have a poor outcome with a common progression to metastasis. Despite improvements in knowledge, treatment has not advanced significantly in recent years, with the absence of new therapeutic targets. Because of the limitations of current therapeutic options, the greater challenge will be to identify biomarkers for clinical application. For this reason, we compared our array comparative genomic hybridization (array-CGH results with those reported in literature for invasive bladder tumors and, in particular, we focused on the evaluation of copy number alterations (CNAs present in biopsies and retained in the corresponding cancer stem cell (CSC subpopulations that should be the main target of therapy. According to our data, CCNE1, MYC, MDM2 and PPARG genes could be interesting therapeutic targets for bladder CSC subpopulations. Surprisingly, HER2 copy number gains are not retained in bladder CSCs, making the gene-targeted therapy less interesting than the others. These results provide precious advice for further study on bladder therapy; however, the clinical importance of these results should be explored.

  14. Economics of Harmful Invasive Species: A Review

    Directory of Open Access Journals (Sweden)

    George Marbuah

    2014-07-01

    Full Text Available The purpose of this study is to review theoretical and empirical findings in economics with respect to the challenging question of how to manage invasive species. The review revealed a relatively large body of literature on the assessment of damage costs of invasive species; single species and groups of species at different geographical scales. However, the estimated damage costs show large variation, from less than 1 million USD to costs corresponding to 12% of gross domestic product, depending on the methods employed, geographical scale, and scope with respect to inclusion of different species. Decisions regarding optimal management strategies, when to act in the invasion chain and which policy to choose, have received much less attention in earlier years, but have been subject to increasing research during the last decade. More difficult, but also more relevant policy issues have been raised, which concern the targeting in time and space of strategies under conditions of uncertainty. In particular, the weighting of costs and benefits from early detection and mitigation against the uncertain avoidance of damage with later control, when the precision in targeting species is typically greater is identified as a key challenge. The role of improved monitoring for detecting species and their spread and damage has been emphasized, but questions remain on how to achieve this in practice. This is in contrast to the relatively large body of literature on policies for mitigating dispersal by trade, which is regarded as one of the most important vectors for the spread of invasive species. On the other hand, the literature on how to mitigate established species, by control or adaptation, is much more scant. Studies evaluating causes for success or failure of policies against invasive in practice are in principal non-existing.

  15. Arithmetic Progressions on Conics

    OpenAIRE

    Ciss, Abdoul Aziz; Moody, Dustin

    2016-01-01

    In this paper, we look at long arithmetic progressions on conics. By an arithmetic progression on a curve, we mean the existence of rational points on the curve whose x-coordinates are in arithmetic progression. We revisit arithmetic progressions on the unit circle, constructing 3-term progressions of points in the first quadrant containing an arbitrary rational point on the unit circle. We also provide infinite families of three term progressions on the unit hyperbola, as well as conics ax2 ...

  16. Dietary Flexibility Aids Asian Earthworm Invasion in North American Forests

    Science.gov (United States)

    On a local scale, invasiveness of introduced species and invasibility of habitats together determine invasion success. A key issue in invasion ecology has been how to quantify the contribution of species invasiveness and habitat invasibility separately. Conventional approaches, s...

  17. Diagnostic criteria in invasive pituitary adenomas

    Directory of Open Access Journals (Sweden)

    Moldovan Ioana-Maria

    2016-09-01

    Full Text Available Pituitary adenomas are benign pituitary primary tumors, the most frequent type of tumor in the pituitary fossa. An important part, around 1/3 of the pituitary adenomas manifests an aggressive behavior, growing faster and invading into parasellar areas (cavernous sinus, neural tissues and bones. Objectives: the first aim of this paper is to review the last findings about invasiveness diagnostic criteria, imagistic and biomarkers, which can be used in the classification of pituitary tumors and also to predict the probability of invasiveness, tumor recurrence and suspicion of malignancy. The second aim is to highlight the morphological and clinic types of invasive pituitary adenomas. Materials and methods: we performed a systematic review and analysis of the published articles, searching PubMed between January 1985 and December 2015. There were selected articles published in English, reviews and abstracts. During the advanced search type in PubMed, combinations of the following keywords were used: “pituitary adenoma”, “invasive”, “aggressive”, “biomarkers”, “classification”, “histological subtypes”, ‘”immunohistochemical markers”. Results: 215 articles were selected, regarding diagnostic, prognostic and therapeutic aspects. There were some histological subtypes of pituitary adenomas known as having an aggressive clinical behavior. Several biomarkers were identified as being associated with the invasive feature: proliferation markers (Ki-67 index, number of mitoses, p53 & p27 expression, microvascularization density, telomerase, topoisomerase 2 Alpha, matrix metalloproteinases, protein kinase C, cyclooxygenase-2, E-cadherin, transcription Factors, genetic alterations (PTTG gene, Galectin-3 protein/ LGALS3 gene, apoptosis markers. Based on their invasion and proliferation characteristics, pituitary tumors are proposed to be classified into five grades (1a, 1b, 2a, 2b, 3, the grade 2b tumor with high risk of recurrence

  18. Ethical issues in invasive mechanical ventilation for amyotrophic lateral sclerosis.

    Science.gov (United States)

    Hirano, Yuko; Yamazaki, Yoshihiko

    2010-01-01

    Currently in Japan, discontinuing an invasive mechanical ventilator (IMV) is illegal; therefore IMV-related decision making is a crucial issue. This study examined IMV decision-making factors and psychological conflict in 50 patients with amyotrophic lateral sclerosis. The Herth Hope Index was used for the assessment of pre- and post-IMV conflict. Interviews identified some decision-making factors: patient's decision, patient's and family's mutual decision, family's decision, and emergency-induced without patient's or family's consent. Participants who experienced no IMV-related regret received sufficient prior IMV education from physicians and nurses, and time for reflection and family consultation. Their hope was similar to their pre-onset levels. Patients who received no prior IMV education accepted treatment as a natural progression. Their hope levels were lower than pre-onset. Those who received only a brief prior IMV explanation rejected the ventilator, experiencing regret if they were given an emergency IMV. Their hope levels were among the lowest. However, some of these patients managed to overcome their regret through being helped by nurses. Sufficient physician explanation and nursing advocacy for autonomous patient decision making are critical for improving hope in this patient group.

  19. Chronic invasive sinus aspergillosis in immunocompetent hosts: a geographic comparison.

    Science.gov (United States)

    Webb, Brandon J; Vikram, Holenarasipur R

    2010-12-01

    To investigate potential differences in clinical presentation, histopathology, and outcomes of chronic invasive sinus aspergillosis (CISA) based on geographic region and species of Aspergillus isolated. A retrospective analysis of published cases of CISA with a comparison of North American and worldwide cases comprised a systematic search of the English language literature. Thirty-four articles were identified detailing 15 North American and 76 global cases of CISA with cranio-cerebral extension in clinically immunocompetent patients. North American patients with CISA were older, had a more rapidly progressive course, and appeared to have higher rates of treatment failure and mortality. Anatomic distribution and presenting symptoms were similar between the two groups. North American cases were mostly due to A. fumigatus, while A. flavus was the predominant pathogen worldwide. While granulomatous inflammation was a rare observation in North American cases, it was seen in the majority of cases worldwide. CISA due to A. fumigatus was encountered in older adults, was associated with a chronic inflammatory response, an accelerated clinical course, and a trend toward treatment failure and higher mortality. Patients with A. flavus were younger, demonstrated granulomatous inflammation, and pursued an indolent, clinically responsive course. Observed differences in clinical presentation, histopathology, and outcome might involve a complex interplay between the human host, Aspergillus species, and local climatic conditions.

  20. Independent Effects of Invasive Shrubs and Deer Herbivory on Plant Community Dynamics

    Directory of Open Access Journals (Sweden)

    Jeffrey S. Ward

    2016-12-01

    Full Text Available Both invasive species and deer herbivory are recognized as locally important drivers of plant community dynamics. However, few studies have examined whether their effects are synergistic, additive, or antagonistic. At three study areas in southern New England, we examined the interaction of white-tailed deer (Odocoileus virginianus Zimmermann herbivory and three levels of invasive shrub control over seven growing seasons on the dynamics of nine herbaceous and shrub guilds. Although evidence of synergistic interactions was minimal, the separate effects of invasive shrub control and deer herbivory on plant community composition and dynamics were profound. Plant communities remained relatively unchanged where invasive shrubs were not treated, regardless if deer herbivory was excluded or not. With increasing intensity of invasive shrub control, native shrubs and forbs became more dominant where deer herbivory was excluded, and native graminoids became progressively more dominant where deer herbivory remained severe. While deer exclusion and intensive invasive shrub control increased native shrubs and forbs, it also increased invasive vines. Restoring native plant communities in areas with both established invasive shrub thickets and severe deer browsing will require an integrated management plan to eliminate recalcitrant invasive shrubs, reduce deer browsing intensity, and quickly treat other opportunistic invasive species.

  1. Microbial ecology of biological invasions

    NARCIS (Netherlands)

    Putten, van der W.H.; Klironomos, J.N.; Wardle, D.A.

    2007-01-01

    Invasive microbes, plants and animals are a major threat to the composition and functioning of ecosystems; however, the mechanistic basis of why exotic species can be so abundant and disruptive is not well understood. Most studies have focused on invasive plants and animals, although few have

  2. Prioritizing invasive plant management strategies

    Science.gov (United States)

    Invasive plants are seriously impacting rangelands by displacing desirable species. Management of these species is expensive and careful allocation of scarce dollars is necessary. Ecologically-based invasive plant management (EBIPM) has the potential to provide an improved decision-making process ...

  3. Interstitial guidance of cancer invasion.

    NARCIS (Netherlands)

    Gritsenko, P.G.; Ilina, O.; Friedl, P.H.

    2012-01-01

    Cancer cell invasion into healthy tissues develops preferentially along pre-existing tracks of least resistance, followed by secondary tissue remodelling and destruction. The tissue scaffolds supporting or preventing guidance of invasion vary in structure and molecular composition between organs. In

  4. Earthworm invasions in the tropics

    Science.gov (United States)

    Grizelle Gonzalez; Ching Yu Huang; Xiaoming Zou; Carlos Rodriguez

    2006-01-01

    The effects and implications of invasive species in belowground terrestrial ecosystems are not well known in comparison with aboveground terrestrial and marine environments. The study of earthworm invasions in the tropics is limited by a lack of taxonomic knowledge and the potential for loss of species in native habitats due to anthropogenic land use change. Alteration...

  5. Predicting progression in primary progressive multiple sclerosis: a 10-year multicenter study

    NARCIS (Netherlands)

    Khaleeli, Z.; Ciccarelli, O.; Manfredonia, F.; Barkhof, F.; Brochet, B.; Cercignani, M.; Dousset, V.; Filippi, M.; Montalban, X.; Polman, C.H.; Rovaris, M.; Rovira, A.; Sastre-Garriga, J.; Vellinga, M.M.; Miller, D.; Thompson, A.

    2008-01-01

    Rates of progression vary widely in primary progressive multiple sclerosis. This multicenter study aimed to identify predictors of progression over 10 years. A total of 101 patients who had been imaged at baseline and 2 years were scored on the expanded disability status scale after 10 years.

  6. LRP-1 promotes cancer cell invasion by supporting ERK and inhibiting JNK signaling pathways.

    Directory of Open Access Journals (Sweden)

    Benoit Langlois

    Full Text Available BACKGROUND: The low-density lipoprotein receptor-related protein-1 (LRP-1 is an endocytic receptor mediating the clearance of various extracellular molecules involved in the dissemination of cancer cells. LRP-1 thus appeared as an attractive receptor for targeting the invasive behavior of malignant cells. However, recent results suggest that LRP-1 may facilitate the development and growth of cancer metastases in vivo, but the precise contribution of the receptor during cancer progression remains to be elucidated. The lack of mechanistic insights into the intracellular signaling networks downstream of LRP-1 has prevented the understanding of its contribution towards cancer. METHODOLOGY/PRINCIPAL FINDINGS: Through a short-hairpin RNA-mediated silencing approach, we identified LRP-1 as a main regulator of ERK and JNK signaling in a tumor cell context. Co-immunoprecipitation experiments revealed that LRP-1 constitutes an intracellular docking site for MAPK containing complexes. By using pharmacological agents, constitutively active and dominant-negative kinases, we demonstrated that LRP-1 maintains malignant cells in an adhesive state that is favorable for invasion by activating ERK and inhibiting JNK. We further demonstrated that the LRP-1-dependent regulation of MAPK signaling organizes the cytoskeletal architecture and mediates adhesive complex turnover in cancer cells. Moreover, we found that LRP-1 is tethered to the actin network and to focal adhesion sites and controls ERK and JNK targeting to talin-rich structures. CONCLUSIONS: We identified ERK and JNK as the main molecular relays by which LRP-1 regulates focal adhesion disassembly of malignant cells to support invasion.

  7. RKIP Inhibits Local Breast Cancer Invasion by Antagonizing the Transcriptional Activation of MMP13.

    Directory of Open Access Journals (Sweden)

    Ila Datar

    Full Text Available Raf Kinase Inhibitory Protein or RKIP was initially identified as a Raf-1 binding protein using the yeast 2-hybrid screen. RKIP inhibits the activation phosphorylation of MEK by Raf-1 by competitively inhibiting the binding of MEK to Raf-1 and thus exerting an inhibitory effect on the Raf-MEK-Erk pathway. RKIP has been identified as a metastasis suppressor gene. Expression of RKIP is low in cancer metastases. Although primary tumor growth remains unaffected, re- expression of RKIP inhibits cancer metastasis. Mechanistically, RKIP constrains metastasis by inhibiting angiogenesis, local invasion, intravasation, and colonization. The molecular mechanism of how RKIP inhibits these individual steps remains undefined. In our present study, using an unbiased PCR based screening and by analyzing DNA microarray expression datasets we observe that the expression of multiple metalloproteases (MMPs including MMP1, MMP3, MMP10 and MMP13 are negatively correlated with RKIP expression in breast cancer cell lines and clinical samples. Since expression of MMPs by cancer cells is important for cancer metastasis, we hypothesize that RKIP may mediate suppression of breast cancer metastasis by inhibiting multiple MMPs. We show that the expression signature of RKIP and MMPs is better at predicting high metastatic risk than the individual gene. Using a combination of loss- and gain-of-function approaches, we find that MMP13 is the cause of RKIP-mediated inhibition of local cancer invasion. Interestingly expression of MMP13 alone is not sufficient to reverse the inhibition of breast cancer cell metastasis to the lung due to the expression of RKIP. We find that RKIP negatively regulates MMP13 through the Erk2 signaling pathway and the repression of MMP13 by RKIP is transcription factor AP-1 independent. Together, our findings indicate that RKIP inhibits cancer cell invasion, in part, via MMP13 inhibition. These data also implicate RKIP in the regulation of MMP

  8. Molecular and Genetic Determinants of Glioma Cell Invasion

    Directory of Open Access Journals (Sweden)

    Kenta Masui

    2017-12-01

    Full Text Available A diffusely invasive nature is a major obstacle in treating a malignant brain tumor, “diffuse glioma”, which prevents neurooncologists from surgically removing the tumor cells even in combination with chemotherapy and radiation. Recently updated classification of diffuse gliomas based on distinct genetic and epigenetic features has culminated in a multilayered diagnostic approach to combine histologic phenotypes and molecular genotypes in an integrated diagnosis. However, it is still a work in progress to decipher how the genetic aberrations contribute to the aggressive nature of gliomas including their highly invasive capacity. Here we depict a set of recent discoveries involving molecular genetic determinants of the infiltrating nature of glioma cells, especially focusing on genetic mutations in receptor tyrosine kinase pathways and metabolic reprogramming downstream of common cancer mutations. The specific biology of glioma cell invasion provides an opportunity to explore the genotype-phenotype correlation in cancer and develop novel glioma-specific therapeutic strategies for this devastating disease.

  9. Plant invasions in mountains: Global lessons for better management

    Science.gov (United States)

    McDougall, K.L.; Khuroo, A.A.; Loope, L.L.; Parks, C.G.; Pauchard, A.; Reshi, Z.A.; Rushworth, I.; Kueffer, C.

    2011-01-01

    Mountains are one of few ecosystems little affected by plant invasions. However, the threat of invasion is likely to increase because of climate change, greater anthropogenic land use, and continuing novel introductions. Preventive management, therefore, will be crucial but can be difficult to promote when more pressing problems are unresolved and predictions are uncertain. In this essay, we use management case studies from 7 mountain regions to identify common lessons for effective preventive action. The degree of plant invasion in mountains was variable in the 7 regions as was the response to invasion, which ranged from lack of awareness by land managers of the potential impact in Chile and Kashmir to well-organized programs of prevention and containment in the United States (Hawaii and the Pacific Northwest), including prevention at low altitude. In Australia, awareness of the threat grew only after disruptive invasions. In South Africa, the economic benefits of removing alien plants are well recognized and funded in the form of employment programs. In the European Alps, there is little need for active management because no invasive species pose an immediate threat. From these case studies, we identify lessons for management of plant invasions in mountain ecosystems: (i) prevention is especially important in mountains because of their rugged terrain, where invasions can quickly become unmanageable; (ii) networks at local to global levels can assist with awareness raising and better prioritization of management actions; (iii) the economic importance of management should be identified and articulated; (iv) public acceptance of management programs will make them more effective; and (v) climate change needs to be considered. We suggest that comparisons of local case studies, such as those we have presented, have a pivotal place in the proactive solution of global change issues. ?? International Mountain Society.

  10. Invasive tightly coupled processor arrays

    CERN Document Server

    LARI, VAHID

    2016-01-01

    This book introduces new massively parallel computer (MPSoC) architectures called invasive tightly coupled processor arrays. It proposes strategies, architecture designs, and programming interfaces for invasive TCPAs that allow invading and subsequently executing loop programs with strict requirements or guarantees of non-functional execution qualities such as performance, power consumption, and reliability. For the first time, such a configurable processor array architecture consisting of locally interconnected VLIW processing elements can be claimed by programs, either in full or in part, using the principle of invasive computing. Invasive TCPAs provide unprecedented energy efficiency for the parallel execution of nested loop programs by avoiding any global memory access such as GPUs and may even support loops with complex dependencies such as loop-carried dependencies that are not amenable to parallel execution on GPUs. For this purpose, the book proposes different invasion strategies for claiming a desire...

  11. Dynamic expression patterns of differential proteins during early invasion of hepatocellular carcinoma.

    Science.gov (United States)

    Chen, Rong-Xin; Song, Hai-Yan; Dong, Yin-Ying; Hu, Chao; Zheng, Qiong-Dan; Xue, Tong-Chun; Liu, Xiao-Hui; Zhang, Yang; Chen, Jie; Ren, Zheng-Gang; Liu, Yin-Kun; Cui, Jie-Feng

    2014-01-01

    Tumor cell invasion into the surrounding matrix has been well documented as an early event of metastasis occurrence. However, the dynamic expression patterns of proteins during early invasion of hepatocellular carcinoma (HCC) are largely unknown. Using a three-dimensional HCC invasion culture model established previously, we investigated the dynamic expression patterns of identified proteins during early invasion of HCC. Highly metastatic MHCC97H cells and a liver tissue fragment were long-term co-cultured in a rotating wall vessel (RWV) bioreactor to simulate different pathological states of HCC invasion. The established spherical co-cultures were collected on days 0, 5, 10, and 15 for dynamic expression pattern analysis. Significantly different proteins among spheroids at different time points were screened and identified using quantitative proteomics of iTRAQ labeling coupled with LC-MS/MS. Dynamic expression patterns of differential proteins were further categorized by K-means clustering. The expression modes of several differentially expressed proteins were confirmed by Western blot and qRT-PCR. Time course analysis of invasion/metastasis gene expressions (MMP2, MMP7, MMP9, CD44, SPP1, CXCR4, CXCL12, and CDH1) showed remarkable, dynamic alterations during the invasion process of HCC. A total of 1,028 proteins were identified in spherical co-cultures collected at different time points by quantitative proteomics. Among these proteins, 529 common differential proteins related to HCC invasion were clustered into 25 types of expression patterns. Some proteins displayed significant dynamic alterations during the early invasion process of HCC, such as upregulation at the early invasion stage and downregulation at the late invasion stage (e.g., MAPRE1, PHB2, cathepsin D, etc.) or continuous upregulation during the entire invasion process (e.g., vitronectin, Met, clusterin, ICAM1, GSN, etc.). Dynamic expression patterns of candidate proteins during the early invasion

  12. Experimental approaches for evaluating the invasion risk of biofuel crops

    International Nuclear Information System (INIS)

    Luke Flory, S; Sollenberger, Lynn E; Lorentz, Kimberly A; Gordon, Doria R

    2012-01-01

    There is growing concern that non-native plants cultivated for bioenergy production might escape and result in harmful invasions in natural areas. Literature-derived assessment tools used to evaluate invasion risk are beneficial for screening, but cannot be used to assess novel cultivars or genotypes. Experimental approaches are needed to help quantify invasion risk but protocols for such tools are lacking. We review current methods for evaluating invasion risk and make recommendations for incremental tests from small-scale experiments to widespread, controlled introductions. First, local experiments should be performed to identify conditions that are favorable for germination, survival, and growth of candidate biofuel crops. Subsequently, experimental introductions in semi-natural areas can be used to assess factors important for establishment and performance such as disturbance, founder population size, and timing of introduction across variable habitats. Finally, to fully characterize invasion risk, experimental introductions should be conducted across the expected geographic range of cultivation over multiple years. Any field-based testing should be accompanied by safeguards and monitoring for early detection of spread. Despite the costs of conducting experimental tests of invasion risk, empirical screening will greatly improve our ability to determine if the benefits of a proposed biofuel species outweigh the projected risks of invasions. (letter)

  13. Invasive Group A Streptococcal Disease: Risk Factors for Adults

    OpenAIRE

    Factor, Stephanie H.; Levine, Orin S.; Schwartz, Benjamin; Harrison, Lee H.; Farley, Monica M.; McGeer, Allison; Schuchat, Anne

    2003-01-01

    We conducted a case-control study to identify risk factors for invasive group A streptococcal (GAS) infections, which can be fatal. Case-patients were identified when Streptoccus pyogenes was isolated from a normally sterile site and control subjects (two or more) were identified and matched to case-patients by using sequential-digit telephone dialing. All participants were noninstitutionalized surveillance area residents, >18 years of age. Conditional logistic regression identified the risk ...

  14. Predicting progression in primary progressive multiple sclerosis: a 10-year multicenter study.

    Science.gov (United States)

    Khaleeli, Zhaleh; Ciccarelli, Olga; Manfredonia, Francesco; Barkhof, Frederik; Brochet, Bruno; Cercignani, Mara; Dousset, Vincent; Filippi, Massimo; Montalban, Xavier; Polman, Chris; Rovaris, Marco; Rovira, Alex; Sastre-Garriga, Jaume; Vellinga, Machteld; Miller, David; Thompson, Alan

    2008-06-01

    Rates of progression vary widely in primary progressive multiple sclerosis. This multicenter study aimed to identify predictors of progression over 10 years. A total of 101 patients who had been imaged at baseline and 2 years were scored on the expanded disability status scale after 10 years. Ordinal logistic regression identified the following independent variables that predicted progression: male sex, shorter disease duration, and slower timed walk test at baseline (best overall predictor), and deterioration in expanded disability status scale score and reduction in brain volume over 2 years. These predictors of long-term disability provide some insight into disease progression.

  15. Novel multisensor probe for monitoring bladder temperature during locoregional chemohyperthermia for nonmuscle-invasive bladder cancer: technical feasibility study

    NARCIS (Netherlands)

    Cordeiro, Ernesto R.; Geijsen, Debby E.; Zum Vörde Sive Vörding, Paul J.; Schooneveldt, Gerben; Sijbrands, Jan; Hulshof, Maarten C.; de la Rosette, Jean; de Reijke, Theo M.; Crezee, Hans

    2013-01-01

    The effectiveness of locoregional hyperthermia combined with intravesical instillation of mitomycin C to reduce the risk of recurrence and progression of intermediate- and high-risk nonmuscle-invasive bladder cancer is currently investigated in clinical trials. Clinically effective locoregional

  16. Complexity of cancer protease biology: Cathepsin K expression and function in cancer progression

    NARCIS (Netherlands)

    Verbovšek, Urška; van Noorden, Cornelis J. F.; Lah, Tamara T.

    2015-01-01

    Proteases, including lysosomal cathepsins, are functionally involved in many processes in cancer progression from its initiation to invasion and metastatic spread. Only recently, cathepsin K (CatK), the cysteine protease originally reported as a collagenolytic protease produced by osteoclasts,

  17. Geothermal progress monitor. Progress report No. 1

    Energy Technology Data Exchange (ETDEWEB)

    1979-12-01

    Progress is reported on the following: electrical uses, direct-heat uses, drilling activities, leases, geothermal loan guarantee program, general activities, and legal, institutional, and regulatory activites. (MHR)

  18. Human MSCs promotes colorectal cancer epithelial-mesenchymal transition and progression via CCL5/β-catenin/Slug pathway.

    Science.gov (United States)

    Chen, Ke; Liu, Qianqian; Tsang, Lai Ling; Ye, Qiao; Chan, Hsiao Chang; Sun, Yunwei; Jiang, Xiaohua

    2017-05-25

    Mesenchymal stem cells (MSCs) extensively interact with cancer cells and other stroma cells in the tumor microenvironment. However, the role of MSCs in colorectal cancer (CRC) progression and metastasis is controversial. This study was designed to identify the role of inflammation-activated-MSCs in CRC development. Our results show that tumor necrosis factor (TNF)-α-preactivated-hMSCs significantly promote the progression of colon cancer cells by enhancing cell proliferation, epithelial-mesenchymal transition, migration, and invasion. TNF-α-primed-hMSCs secrete high level of CCL5, which interacts with its receptor CCR1 expressed in colon cancer cells. Interestingly, the stimulation of colon cancer cell progression by TNF-α-primed hMSCs is associated with the upregulation of β-catenin signaling pathway. Blocking β-catenin pathway significantly decreases the TNF-α-primed-conditioned medium or CCL5-mediated cancer cell progression by decreasing the enhancement of Slug, suggesting that the CCL5/β-catenin/Slug pathway plays a critical role in hMSC-mediated cancer progression. Furthermore, in vivo model in nude mice confirms the ability of hMSCs to promote the proliferation and progression of colon cancer cells, and the upregulation of CCl5/β-catenin/Slug pathway. Taken together, the present study has demonstrated a novel pathway involving CCl5/CCR1/β-catenin/Slug, via which hMSCs promotes CRC development.

  19. Public Perception of Invasive Plant Species: Assessing the Impact of Workshop Activities to Promote Young Students' Awareness

    Science.gov (United States)

    Schreck Reis, Catarina; Marchante, Helia; Freitas, Helena; Marchante, Elizabete

    2013-01-01

    Invasive species are one of the main threats to biodiversity worldwide. Even though they are identified and recognized as such by the Portuguese law, the majority of the population is not yet aware of this problem. Aiming to increase awareness about biological invasions among young students, a workshop on Invasive Plant Species was organized at…

  20. Using forest inventory and analysis data to understand biotic resistance to plant invasions across the Eastern United States

    Science.gov (United States)

    Basil V. III Iannone; Kevin M. Potter; Hao Zhang; Christopher M. Guo Oswalt; Christopher W. Woodall; Songlin. Fei

    2015-01-01

    Biological invasions and their impacts are likely to increase with the expansion of global commerce, making the need to identify key drivers and regulators of invasion perhaps greater than ever. One of the most enduring, and tested, hypotheses for explaining invasions is the “biotic resistance hypothesis.” Broadly, this hypothesis states that communities having greater...

  1. Arithmetic Progressions on Conics.

    Science.gov (United States)

    Ciss, Abdoul Aziz; Moody, Dustin

    2017-01-01

    In this paper, we look at long arithmetic progressions on conics. By an arithmetic progression on a curve, we mean the existence of rational points on the curve whose x -coordinates are in arithmetic progression. We revisit arithmetic progressions on the unit circle, constructing 3-term progressions of points in the first quadrant containing an arbitrary rational point on the unit circle. We also provide infinite families of three term progressions on the unit hyperbola, as well as conics ax 2 + cy 2 = 1 containing arithmetic progressions as long as 8 terms.

  2. [Experiences of Patients with Invasive and Non-Invasive Home Mechanical Ventilation - a Systematic Review of Qualitative Research].

    Science.gov (United States)

    Nelißen, V; Metzing, S; Schnepp, W

    2017-10-18

    Aim of the study  Human beings can be ventilated outside of a hospital after a lung failure or due to a neurodegenerative disease. This can be done in different living conditions. This article examines the question of what experiences such patients have made with invasive home mechanical ventilation, and how they have adapted their new lives. Methodology  On the basis of a systematic literature research, qualitative studies were analyzed that depict the social reality of patients with invasive and non-invasive home mechanical ventilation. Results  Eleven international studies with a qualitative research design could be identified. Studies that investigate the experiences of patients with invasive ventilation in Germany have not yet been published. The analysis led to the following topics: experiencing the start of ventilation, living with ventilation, safety, family life, stigmatization and a life with dependence, but self-determined. Conclusion  Human beings who need to be out of hospital an invasive or non-invasive ventilation, it is difficult to decide for the ventilation and the right time to begin it. With the ventilation, they then connect a positive feeling of life. To enable a self-determined and active life to humans with invasive ventilation, it is important for health care providers to know the needs and to adapt to them individually. © Georg Thieme Verlag KG Stuttgart · New York.

  3. Syndecan-2 promotes perineural invasion and cooperates with K-ras to induce an invasive pancreatic cancer cell phenotype.

    Science.gov (United States)

    De Oliveira, Tiago; Abiatari, Ivane; Raulefs, Susanne; Sauliunaite, Danguole; Erkan, Mert; Kong, Bo; Friess, Helmut; Michalski, Christoph W; Kleeff, Jörg

    2012-04-03

    We have identified syndecan-2 as a protein potentially involved in perineural invasion of pancreatic adenocarcinoma (PDAC) cells. Syndecan-2 (SDC-2) expression was analyzed in human normal pancreas, chronic pancreatitis and PDAC tissues. Functional in vitro assays were carried out to determine its role in invasion, migration and signaling. SDC-2 was expressed in the majority of the tested pancreatic cancer cell lines while it was upregulated in nerve-invasive PDAC cell clones. There were 2 distinct expression patterns of SDC-2 in PDAC tissue samples: SDC-2 positivity in the cancer cell cytoplasm and a peritumoral expression. Though SDC-2 silencing (using specific siRNA oligonucleotides) did not affect anchorage-dependent growth, it significantly reduced cell motility and invasiveness in the pancreatic cancer cell lines T3M4 and Su8686. On the transcriptional level, migration-and invasion-associated genes were down-regulated following SDC-2 RNAi. Furthermore, SDC-2 silencing reduced K-ras activity, phosphorylation of Src and--further downstream--phosphorylation of ERK2 while levels of the putative SDC-2 signal transducer p120GAP remained unaltered. SDC-2 is a novel (perineural) invasion-associated gene in PDAC which cooperates with K-ras to induce a more invasive phenotype.

  4. Syndecan-2 promotes perineural invasion and cooperates with K-ras to induce an invasive pancreatic cancer cell phenotype

    Directory of Open Access Journals (Sweden)

    De Oliveira Tiago

    2012-04-01

    Full Text Available Abstract Background We have identified syndecan-2 as a protein potentially involved in perineural invasion of pancreatic adenocarcinoma (PDAC cells. Methods Syndecan-2 (SDC-2 expression was analyzed in human normal pancreas, chronic pancreatitis and PDAC tissues. Functional in vitro assays were carried out to determine its role in invasion, migration and signaling. Results SDC-2 was expressed in the majority of the tested pancreatic cancer cell lines while it was upregulated in nerve-invasive PDAC cell clones. There were 2 distinct expression patterns of SDC-2 in PDAC tissue samples: SDC-2 positivity in the cancer cell cytoplasm and a peritumoral expression. Though SDC-2 silencing (using specific siRNA oligonucleotides did not affect anchorage-dependent growth, it significantly reduced cell motility and invasiveness in the pancreatic cancer cell lines T3M4 and Su8686. On the transcriptional level, migration-and invasion-associated genes were down-regulated following SDC-2 RNAi. Furthermore, SDC-2 silencing reduced K-ras activity, phosphorylation of Src and - further downstream - phosphorylation of ERK2 while levels of the putative SDC-2 signal transducer p120GAP remained unaltered. Conclusion SDC-2 is a novel (perineural invasion-associated gene in PDAC which cooperates with K-ras to induce a more invasive phenotype.

  5. Description of the Pathogenic Features of Streptococcus pyogenes Isolates from Invasive and Non-Invasive Diseases in Aichi, Japan.

    Science.gov (United States)

    Matsumoto, Masakado; Yamada, Kazuhiro; Suzuki, Masahiro; Adachi, Hirokazu; Kobayashi, Shinichi; Yamashita, Teruo; Minagawa, Hiroko; Tatsuno, Ichiro; Hasegawa, Tadao

    2016-07-22

    We identified hypervirulent Streptococcus pyogenes in 27 and 420 isolates from patients with invasive and non-invasive diseases, respectively, in Aichi Prefecture, Japan, between 2003 and 2012, in an attempt to understand why the prevalence of streptococcal toxic shock syndrome (STSS) suddenly increased in this location during 2011. Hypervirulent strains belong to the emm1 genotype, with a mutation in the covR/S genes that regulate many other genes, encoding virulence determinants and resulting in the absence of the proteinase streptococcal exotoxin B and the production of virulence factors such as the superantigen streptococcal exotoxin A, the nuclease streptococcal DNase, the cytotoxin NAD-glycohydrolase, and the hemolysin streptolysin O. We found 1 strain from invasive disease and 1 from non-invasive disease with traits similar to those of hypervirulent strains, except that the sda1 gene was absent. We also found 1 non-emm1 strain with phenotypic and genetic traits identical to those of the emm1 hypervirulent strains except that it did not belong to emm1 genotype, from non-invasive diseases cases in 2011. These findings suggested that hypervirulent and hypervirulent-like strains from invasive and non-invasive disease cases could have at least partially contributed to the sudden increase in the number of patients with STSS in Aichi during 2011.

  6. Identifying three different architectural subtypes of mammary ductal carcinoma in situ using multiphoton microscopy

    Science.gov (United States)

    Wu, Yan; Fu, Fangmeng; Lian, Yuane; Nie, Yuting; Zhuo, shuangmu; Wang, Chuan; Chen, Jianxin

    2015-10-01

    Ductal carcinoma in situ (DCIS) is often considered as the precursor of invasive breast cancer, and the risk of DCIS progression to IBC has been estimated based on the evaluation of pathological features, among which the architectural subtype is the most common one. In this study, multiphoton microscopy (MPM) is applied to identify three different architectural subtypes of DCIS (solid, cribriform and comedo). It is found that MPM has the capability to visualize the proliferating pattern of tumor cells, the presence of intraluminal necrosis and the morphology of basement membrane, which are all taken into account in subtyping DCIS. In addition, MPM also can be used to quantify the cellular metabolism, for quantitatively identifying tumor staging during tumor progression. This result highlights the potential of MPM as an advanced technique to assess the pathological characters of the breast tumor in real-time and reflect the degree of tumor progression in vivo, by integrating into the intra-fiberoptic ductoscopy or transdermal biopsy needle.

  7. Evidence of climatic niche shift during biological invasion.

    Science.gov (United States)

    Broennimann, O; Treier, U A; Müller-Schärer, H; Thuiller, W; Peterson, A T; Guisan, A

    2007-08-01

    Niche-based models calibrated in the native range by relating species observations to climatic variables are commonly used to predict the potential spatial extent of species' invasion. This climate matching approach relies on the assumption that invasive species conserve their climatic niche in the invaded ranges. We test this assumption by analysing the climatic niche spaces of Spotted Knapweed in western North America and Europe. We show with robust cross-continental data that a shift of the observed climatic niche occurred between native and non-native ranges, providing the first empirical evidence that an invasive species can occupy climatically distinct niche spaces following its introduction into a new area. The models fail to predict the current invaded distribution, but correctly predict areas of introduction. Climate matching is thus a useful approach to identify areas at risk of introduction and establishment of newly or not-yet-introduced neophytes, but may not predict the full extent of invasions.

  8. Differences in cap formation between invasive Entamoeba histolytica and non-invasive Entamoeba dispar.

    Science.gov (United States)

    Chávez-Munguía, Bibiana; Talamás-Rohana, Patricia; Castañón, Guadalupe; Salazar-Villatoro, Lizbeth; Hernández-Ramírez, Verónica; Martínez-Palomo, Adolfo

    2012-07-01

    The rapid redistribution of surface antigen-antibody complexes in trophozoites of the human protozoan parasite Entamoeba histolytica, in a process known as capping, has been considered as a means of the parasite to evade the host immune response. So far, capping has been documented in the invasive E. histolytica, whereas the mobility of surface components in the non-invasive Entamoeba dispar is not known. E. dispar does not induce liver lesions in rodent experimental models, in contrast to the liver abscesses produced by E. histolytica in the same animal model. We have therefore analyzed the mobility of surface receptors to the lectin concanavalin A and of Rab11, a membrane-associated protein, in both species of Entamoebae by confocal fluorescence microscopy and transmission and scanning electron microscopy. The great majority of E. histolytica trophozoites became morphologically polarized through the formation of well-defined caps at the posterior pole of the parasite. Actin colocalized with the lectin caps. Antibodies against the membrane protein Rab 11 also produced capping. In striking contrast, in E. dispar, the mobility of concanavalin A surface receptors was restricted to the formation of irregular surface patches that did no progress to constitute well-defined caps. Also, anti-Rab 11 antibodies did not result in capping in E. dispar. Whether the failure of E. dispar to efficiently mobilize surface molecules in response to lectin or antibodies as shown in the present results is related to its non-invasive character represents an interesting hypothesis requiring further analysis.

  9. Natural biology and management of nonmuscle invasive bladder cancer

    DEFF Research Database (Denmark)

    Scarpato, Kristen R; Tyson, Mark D; Clark, Peter E

    2016-01-01

    PURPOSE OF REVIEW: This article reviews the natural biology of noninvasive bladder cancer and its management strategies while summarizing the most recent advances in the field. RECENT FINDINGS: Nonmuscle invasive bladder cancer (NMIBC) has a tendency to recur and progress. Risk stratification has...... helped triage patients but improved tools, including biomarkers, are still needed. Enhanced endoscopy with photodynamic imaging, narrow band imaging, optical coherence tomography and confocal laser endomicroscopy show promise for diagnosis, risk stratification and disease monitoring. Attempts at better...

  10. Non-muscle invasive bladder cancer risk stratification

    Directory of Open Access Journals (Sweden)

    Sumit Isharwal

    2015-01-01

    Conclusion: EORTC and CUETO risk tables are the two best-established models to predict recurrence and progression in patients with NMIBC though they tend to overestimate risk and have poor discrimination for prognostic outcomes in external validation. Future research should focus on enhancing the predictive accuracy of risk assessment tools by incorporating additional prognostic factors such as depth of lamina propria invasion and molecular biomarkers after rigorous validation in multi-institutional cohorts.

  11. Overexpression of ErbB2 induces invasion of MCF10A human breast epithelial cells via MMP-9.

    Science.gov (United States)

    Kim, In-Young; Yong, Hae-Young; Kang, Keon Wook; Moon, Aree

    2009-03-18

    Metastasis is the principal cause of death from breast cancer. ErbB2 (HER-2/neu) has been identified as an important regulator of metastatic potential of breast cancer. The present study investigated the molecular mechanism underlying the role of ErbB2 in malignant phenotypic conversion of MCF10A human breast epithelial cells which originally have 'normal' cell character. Here we report that ErbB2 induces invasion and migration of MCF10A cells though up-regulation of matrix metalloproteinase (MMP)-9. We also observed a marked reduction of an epithelial cell marker, E-cadherin, and an induction of vimentin in ErbB2-MCF10A cells, suggesting that epithelial-mesenchymal transition may play a role in the ErbB2-induced invasion and migration of MCF10A cells. Overexpression of ErbB2 significantly activated p38 MAPK and Akt, while Raf-1/MEK/ERK pathway was not activated by ErbB2. Using pharmacological inhibitors, we further show that p38 MAPK and Akt signaling pathways are crucial for the ErbB2-induced MMP-9 up-regulation, invasion and migration of MCF10A cells. Given that ErbB2 is one of the most important oncogenes in human breast cancer and thus is an attractive therapeutic target, our findings may provide a molecular basis for the promoting role of ErbB2 in breast cancer progression.

  12. CRISPR-Cas9 Mediated NOX4 Knockout Inhibits Cell Proliferation and Invasion in HeLa Cells.

    Directory of Open Access Journals (Sweden)

    Naser Jafari

    Full Text Available Increased expression of NOX4 protein is associated with cancer progression and metastasis but the role of NOX4 in cell proliferation and invasion is not fully understood. We generated NOX4 knockout HeLa cell lines using the CRISPR-Cas9 gene editing system to explore the cellular functions of NOX4. After transfection of CRISPR-Cas9 construct, we performed T7 endonuclease 1 assays and DNA sequencing to generate and identify insertion and deletion of the NOX4 locus. We confirmed the knockout of NOX4 by Western blotting. NOX4 knockout cell lines showed reduced cell proliferation with an increase of sub-G1 cell population and the decrease of S/G2/M population. Moreover, NOX4 deficiency resulted in a dramatic decrease in invadopodium formation and the invasive activity. In addition, NOX4 deficiency also caused a decrease in focal adhesions and cell migration in HeLa cells. These results suggest that NOX4 is required for both efficient proliferation and invasion of HeLa cells.

  13. Invasive meningococcal disease

    Directory of Open Access Journals (Sweden)

    Vanessa L. Strelow

    2013-09-01

    Full Text Available Invasive meningococcal disease (IMD is a major public health and continues to cause substantial mortality and morbidity. Serotype C is the most frequent in Brazil. The clinical spectrum of IMD is broad (meningitis, meningococcemia or both and the clinical evolution may be unpredictable. Main features associated with mortality are: age higher than 50 years old, seizures, shock, and meningococcemia without meningitis. Blood cultures should be obtained immediately. Lumbar puncture can be performed without previous computed tomography scan (CT in most cases. Clinical features can be useful to predic patients where an abnormal CT scan is likely. Cerebrospinal fluid (CSF culture and Gram stain should always be required. Latex agglutination sensitivity is highly variable. Polymerase chain reaction is specially useful when other methods are negative or delayed. Usually ceftriaxone should not be delayed while awaiting CSF study or CT. Dexamethasone can be used in meningococcal meningitis. Early suspicion of IMD and antibiotic in primary care before hospitalization, rapid transportation to a hospital, and stabilization in an intensive-care unit has substantially reduced the case-fatality rate. Vaccines against serotypes A, C, W-135, and Y are available while vaccines against serotype B are expected.

  14. Integrin laminin receptors and breast carcinoma progression.

    Science.gov (United States)

    Mercurio, A M; Bachelder, R E; Chung, J; O'Connor, K L; Rabinovitz, I; Shaw, L M; Tani, T

    2001-07-01

    This review explores the mechanistic basis of breast carcinoma progression by focusing on the contribution of integrins. Integrins are essential for progression not only for their ability to mediate physical interactions with extracellular matrices but also for their ability to regulate signaling pathways that control actin dynamics and cell movement, as well as for growth and survival. Our comments center on the alpha6 integrins (alpha6beta1 and alpha6beta4), which are receptors for the laminin family of basement membrane components. Numerous studies have implicated these integrins in breast cancer progression and have provided a rationale for studying the mechanistic basis of their contribution to aggressive disease. Recent work by our group and others on mechanisms of breast carcinoma invasion and survival that are influenced by the alpha6 integrins are discussed.

  15. Invasion of Human Oral Epithelial Cells by Prevotella intermedia

    Science.gov (United States)

    Dorn, Brian R.; Leung, K.-P.; Progulske-Fox, Ann

    1998-01-01

    Invasion of oral epithelial cells by pathogenic oral bacteria may represent an important virulence factor in the progression of periodontal disease. Here we report that a clinical isolate of Prevotella intermedia, strain 17, was found to invade a human oral epithelial cell line (KB), whereas P. intermedia 27, another clinical isolate, and P. intermedia 25611, the type strain, were not found to invade the cell line. Invasion was quantified by the recovery of viable bacteria following a standard antibiotic protection assay and observed by electron microscopy. Cytochalasin D, cycloheximide, monodansylcadaverine, and low temperature (4°C) inhibited the internalization of P. intermedia 17. Antibodies raised against P. intermedia type C fimbriae and against whole cells inhibited invasion, but the anti-type-C-fimbria antibody inhibited invasion to a greater extent than the anti-whole-cell antibody. This work provides evidence that at least one strain of P. intermedia can invade an oral epithelial cell line and that the type C fimbriae and a cytoskeletal rearrangement are required for this invasion. PMID:9826397

  16. Non-invasive hemoglobin monitoring.

    Science.gov (United States)

    Joseph, Bellal; Haider, Ansab; Rhee, Peter

    2016-09-01

    Technology has transformed the practice of medicine and surgery in particular over the last several decades. This change in practice has allowed diagnostic and therapeutic tests to be performed less invasively. Hemoglobin monitoring remains one of the most commonly performed diagnostic tests in the United States. Recently, non-invasive hemoglobin monitoring technology has gained popularity. The aim of this article is to review the principles of how this technology works, pros and cons, and the implications of non-invasive hemoglobin technology particularly in trauma surgery. Copyright © 2015 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

  17. Association of diabetes and perineural invasion in pancreatic cancer.

    Science.gov (United States)

    Sahin, Ibrahim Halil; Shama, Mohamed A; Tanaka, Motofumi; Abbruzzese, James L; Curley, Steven A; Hassan, Manal; Li, Donghui

    2012-12-01

    Diabetes and perineural invasion are frequently observed in pancreatic cancer. In this study, we tested possible relations between diabetes and perineural invasion in patients with resected pancreatic cancer. We conducted a retrospective study in 544 cases of resected pancreatic adenocarcinoma seen at the University of Texas MD Anderson Cancer Center during 1996-2011. Information on tumor characteristics, diabetes history, and survival time was collected by personal interview and medical record review. Patients with diabetes before or at the time of the pancreatic cancer diagnosis were considered diabetes only. Pearson χ(2) test was used to compare categorical variables in diabetic and nondiabetic groups. Kaplan-Meier plot, log-rank test, and Cox proportional regression models were applied in survival analysis. The prevalence of diabetes and perineural invasion was 26.5% and 86.9%, respectively, in this study population. Patients with diabetes had a significantly higher prevalence of perineural invasion (92.4%) than those without diabetes (85%) (P = 0.025, χ(2) test). Diabetes was not associated with other pathological characteristics of the tumor, such as tumor size, lymphovascular invasion, tumor grade, lymph node metastasis, and resection margin status. Diabetic patients had a significantly lower frequency of abdominal pain (P = 0.01), but a slightly higher frequency of weight loss (P = 0.078) as early symptoms of their cancer. Both diabetes and perineural invasion were related to worse survival and increased risk of death after adjusting for tumor grade and margin and node status (P = 0.036 and 0.019, respectively). The observed associations of diabetes and perineural invasion as well as reduced frequency of pain as early symptom of pancreatic cancer support the hypothesis that diabetes may contribute to pancreatic progression via the mechanism of nerve damage.

  18. Live attenuated vaccines for invasive Salmonella infections.

    Science.gov (United States)

    Tennant, Sharon M; Levine, Myron M

    2015-06-19

    Salmonella enterica serovar Typhi produces significant morbidity and mortality worldwide despite the fact that there are licensed Salmonella Typhi vaccines available. This is primarily due to the fact that these vaccines are not used in the countries that most need them. There is growing recognition that an effective invasive Salmonella vaccine formulation must also prevent infection due to other Salmonella serovars. We anticipate that a multivalent vaccine that targets the following serovars will be needed to control invasive Salmonella infections worldwide: Salmonella Typhi, Salmonella Paratyphi A, Salmonella Paratyphi B (currently uncommon but may become dominant again), Salmonella Typhimurium, Salmonella Enteritidis and Salmonella Choleraesuis (as well as other Group C Salmonella). Live attenuated vaccines are an attractive vaccine formulation for use in developing as well as developed countries. Here, we describe the methods of attenuation that have been used to date to create live attenuated Salmonella vaccines and provide an update on the progress that has been made on these vaccines. Copyright © 2015. Published by Elsevier Ltd.

  19. [Theory and practice of minimally invasive endodontics].

    Science.gov (United States)

    Jiang, H W

    2016-08-01

    The primary goal of modern endodontic therapy is to achieve the long-term retention of a functional tooth by preventing or treating pulpitis or apical periodontitis is. The long-term retention of endodontically treated tooth is correlated with the remaining amount of tooth tissue and the quality of the restoration after root canal filling. In recent years, there has been rapid progress and development in the basic research of endodontic biology, instrument and applied materials, making treatment procedures safer, more accurate, and more efficient. Thus, minimally invasive endodontics(MIE)has received increasing attention at present. MIE aims to preserve the maximum of tooth structure during root canal therapy, and the concept covers the whole process of diagnosis and treatment of teeth. This review article focuses on describing the minimally invasive concepts and operating essentials in endodontics, from diagnosis and treatment planning to the access opening, pulp cavity finishing, root canal cleaning and shaping, 3-dimensional root canal filling and restoration after root canal treatment.

  20. β-catenin is required for prostate development and cooperates with Pten loss to drive invasive carcinoma.

    Directory of Open Access Journals (Sweden)

    Jeffrey C Francis

    Full Text Available Prostate cancer is a major cause of male death in the Western world, but few frequent genetic alterations that drive prostate cancer initiation and progression have been identified. β-Catenin is essential for many developmental processes and has been implicated in tumorigenesis in many tissues, including prostate cancer. However, expression studies on human prostate cancer samples are unclear on the role this protein plays in this disease. We have used in vivo genetic studies in the embryo and adult to extend our understanding of the role of β-Catenin in the normal and neoplastic prostate. Our gene deletion analysis revealed that prostate epithelial β-Catenin is required for embryonic prostate growth and branching but is dispensable in the normal adult organ. During development, β-Catenin controls the number of progenitors in the epithelial buds and regulates a discrete network of genes, including c-Myc and Nkx3.1. Deletion of β-Catenin in a Pten deleted model of castration-resistant prostate cancer demonstrated it is dispensable for disease progression in this setting. Complementary overexpression experiments, through in vivo protein stabilization, showed that β-Catenin promotes the formation of squamous epithelia during prostate development, even in the absence of androgens. β-Catenin overexpression in combination with Pten loss was able to drive progression to invasive carcinoma together with squamous metaplasia. These studies demonstrate that β-Catenin is essential for prostate development and that an inherent property of high levels of this protein in prostate epithelia is to drive squamous fate differentiation. In addition, they show that β-Catenin overexpression can promote invasive prostate cancer in a clinically relevant model of this disease. These data provide novel information on cancer progression pathways that give rise to lethal prostate disease in humans.

  1. Invasive aquarium fish transform ecosystem nutrient dynamics

    Science.gov (United States)

    Capps, Krista A.; Flecker, Alexander S.

    2013-01-01

    Trade of ornamental aquatic species is a multi-billion dollar industry responsible for the introduction of myriad fishes into novel ecosystems. Although aquarium invaders have the potential to alter ecosystem function, regulation of the trade is minimal and little is known about the ecosystem-level consequences of invasion for all but a small number of aquarium species. Here, we demonstrate how ecological stoichiometry can be used as a framework to identify aquarium invaders with the potential to modify ecosystem processes. We show that explosive growth of an introduced population of stoichiometrically unique, phosphorus (P)-rich catfish in a river in southern Mexico significantly transformed stream nutrient dynamics by altering nutrient storage and remineralization rates. Notably, changes varied between elements; the P-rich fish acted as net sinks of P and net remineralizers of nitrogen. Results from this study suggest species-specific stoichiometry may be insightful for understanding how invasive species modify nutrient dynamics when their population densities and elemental composition differ substantially from native organisms. Risk analysis for potential aquarium imports should consider species traits such as body stoichiometry, which may increase the likelihood that an invasion will alter the structure and function of ecosystems. PMID:23966642

  2. Thymoma and minimally invasive surgical treatment

    International Nuclear Information System (INIS)

    Krajc, T.; Spalek, P.; Lucenic, M.; Benej, R.; Harustiak, S.

    2011-01-01

    The authors review the current thymoma classification schemes, diagnosis and surgical treatment options. Many minimally invasive techniques do not provide sufficient extensiveness when compared to complete sternotomy. The Zieliński technique combines transcervical, subxiphoidal and bilateral thoracoscopic approach in a hybrid procedure (MMIT, maximal minimally invasive thymectomy) based on double sternal traction, and allows for removal of the thymus gland, the thymoma and all the relevant mediastinal adipose tissue, thus adhering to principles of oncological radicality. Of the 28 patients undergoing MMIT there were 7 with myasthenia associated thymoma (MGAT) and 5 with a thymoma and no myasthenia, tumors staged Masaoka I-II. Apart from one temporary recurrent nerve palsy there were no postoperative complications. The largest thymoma measured 70 x 65 x 55 mm. Adjuvant radiotherapy was applied in 5 patients. Ectopic thymic tissue was identified in 100 % of patients with thymoma and no myasthenia and in 42.9 % of MGAT patients. Until now there were no recurrences, however, the follow-up median is very short, the longest follow-up period being 30 months. MMIT is a safe technique suitable also for Masaoka I-II thymoma patients and for some specific cases with Masaoka III stage (lung parenchyma invasion). The authors approach all the anterior mediastinal tumors with no mediastinal lymphadenopathy and no myasthenia as a potential thymoma and always attempt the MMIT procedure starting as VATS procedure on the side of tumor. (author)

  3. Macrophage Capping Protein CapG Is a Putative Oncogene Involved in Migration and Invasiveness in Ovarian Carcinoma

    Directory of Open Access Journals (Sweden)

    J. Glaser

    2014-01-01

    Full Text Available The actin binding protein CapG modulates cell motility by interacting with the cytoskeleton. CapG is associated with tumor progression in different nongynecologic tumor entities and overexpression in breast cancer cell lines correlates with a more invasive phenotype in vitro. Here, we report a significant CapG overexpression in 18/47 (38% of ovarian carcinomas (OC analyzed by qRealTime-PCR analyses. Functional analyses in OC cell lines through siRNA mediated CapG knockdown and CapG overexpression showed CapG-dependent cell migration and invasiveness. A single nucleotide polymorphism rs6886 inside the CapG gene was identified, affecting a CapG phosphorylation site and thus potentially modifying CapG function. The minor allele frequency (MAF of SNP rs6886 (c.1004A/G was higher and the homozygous (A/A, His335 genotype was significantly more prevalent in patients with fallopian tube carcinomas (50% as in controls (10%. With OC being one of the most lethal cancer diseases, the detection of novel biomarkers such as CapG could reveal new diagnostic and therapeutic targets. Moreover, in-depth analyses of SNP rs6886 related to FTC and OC will contribute to a better understanding of carcinogenesis and progression of OC.

  4. Blocking Myristoylation of Src Inhibits Its Kinase Activity and Suppresses Prostate Cancer Progression.

    Science.gov (United States)

    Kim, Sungjin; Alsaidan, Omar Awad; Goodwin, Octavia; Li, Qianjin; Sulejmani, Essilvo; Han, Zhen; Bai, Aiping; Albers, Thomas; Beharry, Zanna; Zheng, Y George; Norris, James S; Szulc, Zdzislaw M; Bielawska, Alicja; Lebedyeva, Iryna; Pegan, Scott D; Cai, Houjian

    2017-12-15

    Protein N -myristoylation enables localization to membranes and helps maintain protein conformation and function. N -myristoyltransferases (NMT) catalyze co- or posttranslational myristoylation of Src family kinases and other oncogenic proteins, thereby regulating their function. In this study, we provide genetic and pharmacologic evidence that inhibiting the N -myristoyltransferase NMT1 suppresses cell-cycle progression, proliferation, and malignant growth of prostate cancer cells. Loss of myristoylation abolished the tumorigenic potential of Src and its synergy with androgen receptor in mediating tumor invasion. We identified the myristoyl-CoA analogue B13 as a small-molecule inhibitor of NMT1 enzymatic activity. B13 exposure blocked Src myristoylation and Src localization to the cytoplasmic membrane, attenuating Src-mediated oncogenic signaling. B13 exerted its anti-invasive and antitumor effects against prostate cancer cells, with minimal toxic side-effects in vivo Structural optimization based on structure-activity relationships enabled the chemical synthesis of LCL204, with enhanced inhibitory potency against NMT1. Collectively, our results offer a preclinical proof of concept for the use of protein myristoylation inhibitors as a strategy to block prostate cancer progression. Cancer Res; 77(24); 6950-62. ©2017 AACR . ©2017 American Association for Cancer Research.

  5. Contortrostatin, a dimeric disintegrin from Agkistrodon contortrix contortrix, inhibits breast cancer progression.

    Science.gov (United States)

    Zhou, Q; Sherwin, R P; Parrish, C; Richters, V; Groshen, S G; Tsao-Wei, D; Markland, F S

    2000-06-01

    We report the results of a multidisciplinary study on the inhibitory effect of a snake venom disintegrin, contortrostatin, a 13.5 kDa homodimeric protein isolated from Agkistrodon contortrix contortrix (southern copperhead) venom, on breast cancer progression. We demonstrate that contortrostatin binds to integrins and blocks the adhesion of human breast cancer cells (MDA-MB-435) to extracellular matrix (ECM) proteins including fibronectin and vitronectin, but it has no effect on adhesion of the cells to laminin and Matrigel. Contortrostatin also prevents invasion of MDA-MB-435 cells through an artificial Matrigel basement membrane. Daily local injection of contortrostatin (5 microg per mouse per day) into MDA-MB-435 tumor masses in an orthotopic xenograft nude mouse model inhibits growth of the tumor by 74% (p = 0.0164). More importantly, it reduces the number of pulmonary macro-metastasis of the breast cancer by 68% (p cancer cells, and does not inhibit proliferation of the breast cancer cells in vitro. However, contortrostatin inhibits angiogenesis induced by the breast cancer, as shown by immunohistochemical quantitation of the vascular endothelial cells in tumor tissue removed from the nude mice. We have identified alpha(v)beta3, an important integrin mediating cell motility and tumor invasion, as one of the binding sites of contortrostatin on MDA-MB-435 cells. We conclude that contortrostatin blocks alpha(v)beta3, and perhaps other integrins, and thus inhibits in vivo progression.

  6. miR-195 Inhibits Tumor Progression by Targeting RPS6KB1 in Human Prostate Cancer.

    Science.gov (United States)

    Cai, Chao; Chen, Qing-Biao; Han, Zhao-Dong; Zhang, Yan-Qiong; He, Hui-Chan; Chen, Jia-Hong; Chen, Yan-Ru; Yang, Sheng-Bang; Wu, Yong-Ding; Zeng, Yan-Ru; Qin, Guo-Qiang; Liang, Yu-Xiang; Dai, Qi-Shan; Jiang, Fu-Neng; Wu, Shu-lin; Zeng, Guo-Hua; Zhong, Wei-De; Wu, Chin-Lee

    2015-11-01

    To investigate the involvement of hsa-miRNA-195-5p (miR-195) in progression and prognosis of human prostate cancer. qRT-PCR was performed to detect miR-195 expression in both prostate cancer cell lines and clinical tissue samples. Its clinical significance was statistically analyzed. The roles of miR-195 and its candidate target gene, ribosomal protein S6 kinase, 70 kDa, polypeptide 1 (RPS6KB1) in prostate cancer progression were confirmed on the basis of both in vitro and in vivo systems. miR-195 downregulation in prostate cancer tissues was significantly associated with high Gleason score (P = 0.001), positive metastasis failure (P biochemical recurrence (BCR, P cancer patients (P = 0.022). Then, we confirmed the tumor suppressive role of miR-195 through prostate cancer cell invasion, migration, and apoptosis assays in vitro, along with tumor xenograft growth, angiogenesis, and invasion in vivo according to both gain-of-function and loss-of-function experiments. In addition, RPS6KB1 was identified as a novel direct target of miR-195 through proteomic expression profiling combined with bioinformatic target prediction and luciferase reporter assay. Moreover, the reexpression and knockdown of RPS6KB1 could respectively rescue and imitate the effects induced by miR-195. Importantly, RPS6KB1 expression was closely correlated with aggressive progression and poor prognosis in prostate cancer patients as opposed to miR-195. Furthermore, we identified MMP-9, VEGF, BAD, and E-cadherin as the downstream effectors of miR-195-RPS6KB1 axis. The newly identified miR-195-RPS6KB1 axis partially illustrates the molecular mechanism of prostate cancer progression and represents a novel potential therapeutic target for prostate cancer treatment. ©2015 American Association for Cancer Research.

  7. Optic nerve invasion of uveal melanoma: clinical characteristics and metastatic pattern

    DEFF Research Database (Denmark)

    Lindegaard, Jacob; Isager, Peter; Prause, Jan Ulrik

    2006-01-01

    PURPOSE: To determine the frequency of optic nerve invasion in uveal melanoma, to identify clinical factors associated with optic nerve invasion, and to analyze the metastatic pattern and the association with survival. METHODS: All iris, ciliary body, and choroidal melanomas (N = 2758) examined...... between 1942 and 2001 at the Eye Pathology Institute, University of Copenhagen, Denmark, and the Institute of Pathology, Aarhus University Hospital, Aarhus, Denmark, were reviewed. Cases with optic nerve invasion were identified and subdivided into prelaminar or laminar invasion and postlaminar invasion....... Clinical characteristics were compared with those from 85 cases randomly drawn from all ciliary body and choroidal melanomas without optic nerve invasion from the same period. Survival data were obtained by the Kaplan-Meier method, and the Mantel-Cox log-rank test was used to test differences in survival...

  8. Biogas Opportunities Roadmap Progress Report

    Energy Technology Data Exchange (ETDEWEB)

    None, None

    2015-12-01

    In support of the Obama Administration's Climate Action Plan, the U.S. Department of Energy, the U.S. Environmental Protection Agency, and U.S. Department of Agriculture jointly released the Biogas Opportunities Roadmap Progress Report, updating the federal government's progress to reduce methane emissions through biogas systems since the Biogas Opportunities Roadmap was completed by the three agencies in July 2014. The report highlights actions taken, outlines challenges and opportunities, and identifies next steps to the growth of a robust biogas industry.

  9. Hypoxia and the Presence of Human Vascular Endothelial Cells Affect Prostate Cancer Cell Invasion and Metabolism

    Directory of Open Access Journals (Sweden)

    Ellen Ackerstaff

    2007-12-01

    Full Text Available Tumor progression and metastasis are influenced by hypoxia, as well as by interactions between cancer cells and components of the stroma, such as endothelial cells. Here, we have used a magnetic resonance (MRcompatible invasion assay to further understand the effects of hypoxia on human prostate cancer cell invasion and metabolism in the presence and absence of human umbilical vein endothelial cells (HUVECs. Additionally, we compared endogenous activities of selected proteases related to invasion in PC-3 cells and HUVECs, profiled gene expression of PC-3 cells by microarray, evaluated cell proliferation of PC-3 cells and HUVECs by flow cytometry, under hypoxic and oxygenated conditions. The invasion of less-invasive DU-145 cells was not affected by either hypoxia or the presence of HUVECs. However, hypoxia significantly decreased the invasion of PC-3 cells. This hypoxia-induced decrease was attenuated by the presence of HUVECs, whereas under oxygenated conditions, HUVECs did not alter the invasion of PC-3 cells. Cell metabolism changed distinctly with hypoxia and invasion. The endogenous activity of selected extracellular proteases, although altered by hypoxia, did not fully explain the hypoxia-induced changes in invasion. Gene expression profiling indicated that hypoxia affects multiple cellular functions and pathways.

  10. A Landscape Approach to Invasive Species Management.

    Directory of Open Access Journals (Sweden)

    Miguel Lurgi

    distributed links. Our modelling framework provides a simple approach for identifying the best possible management strategy for invasive species based on metapopulation structure and control capacity. This information can be used by managers trying to devise efficient landscape-oriented management strategies for invasive species and can also generate insights for conservation purposes.

  11. Gastric metastasis from invasive lobular breast cancer, mimicking primary gastric cancer: A case report.

    Science.gov (United States)

    Kim, Dae Hoon; Son, Seung-Myoung; Choi, Young Jin

    2018-03-01

    Gastric metastasis from invasive lobular breast cancer is relatively rare, commonly presented among multiple metastases, several years after primary diagnosis of breast cancer. Importantly, gastric cancer that is synchronously presented with lobular breast cancer can be misdiagnosed as primary gastric cancer; therefore, accurate differential diagnosis is required. A 39-year-old woman was visited to our hospital because of right breast mass and progressive dyspepsia. Invasive lobular carcinoma of breast was diagnosed on core needle biopsy. Gastroscopy revealed a diffuse scirrhous mass at the prepyloric antrum and diagnosed as poorly differentiated adenocarcinoma on biopsy. Synchronous double primary breast and gastric cancers were considered. Detailed pathological analysis focused on immunohistochemical studies of selected antibodies, including those of estrogen receptors, gross cystic disease fluid protein-15, and caudal-type homeobox transcription factor 2, were studied. As a result, gastric lesion was diagnosed as metastatic gastric cancer originating from breast. Right breast conserving surgery was performed, and duodenal stent was inserted under endoscopic guidance to relieve the patient's symptoms. Systemic chemotherapy with combined administration of paclitaxel and trastuzumab was initiated. Forty-one months after the diagnosis, the patient is still undergoing the same therapy. No recurrent lesion has been identified in the breast and evidence of a partial remission of gastric wall thickening has been observed on follow-up studies without new metastatic lesions. Clinical suspicion, repeat endoscopic biopsy, and detailed histological analysis, including immunohistochemistry, are necessary for diagnosis of metastatic gastric cancer from the breast.

  12. The Atypical Kinase RIOK1 Promotes Tumor Growth and Invasive Behavior

    Directory of Open Access Journals (Sweden)

    Florian Weinberg

    2017-06-01

    Full Text Available Despite being overexpressed in different tumor entities, RIO kinases are hardly characterized in mammalian cells. We investigated the role of these atypical kinases in different cancer cells. Using isogenic colon-, breast- and lung cancer cell lines, we demonstrate that knockdown of RIOK1, but not of RIOK2 or RIOK3, strongly impairs proliferation and invasiveness in conventional and 3D culture systems. Interestingly, these effects were mainly observed in RAS mutant cancer cells. In contrast, growth of RAS wildtype Caco-2 and Bcr-Abl-driven K562 cells is not affected by RIOK1 knockdown, suggesting a specific requirement for RIOK1 in the context of oncogenic RAS signaling. Furthermore, we show that RIOK1 activates NF-κB signaling and promotes cell cycle progression. Using proteomics, we identified the pro-invasive proteins Metadherin and Stathmin1 to be regulated by RIOK1. Additionally, we demonstrate that RIOK1 promotes lung colonization in vivo and that RIOK1 is overexpressed in different subtypes of human lung- and breast cancer. Altogether, our data suggest RIOK1 as a potential therapeutic target, especially in RAS-driven cancers.

  13. Increased beta1 integrin is associated with decreased survival in invasive breast cancer.

    Science.gov (United States)

    Yao, Evelyn S; Zhang, Hui; Chen, Yunn-Yi; Lee, Brian; Chew, Karen; Moore, Dan; Park, Catherine

    2007-01-15

    Aberrant microenvironments and loss of balance in cell-extracellular matrix signaling are associated with breast cancer invasion, metastasis, and resistance to therapy. We have recently shown that increased beta1 integrin signaling is involved in malignant progression and that inhibitory antibody to beta1 integrin leads to selective apoptosis and decreased proliferation in three-dimensional cultures and in xenograft models of breast cancer in vivo. To investigate the clinical importance of these findings, in the present study we examined the expression of beta1 integrin and extracellular beta1 integrin ligands fibronectin and laminin-1 in a cohort of 249 breast cancer patients who had a median follow-up of 8.4 years. Among the 149 scorable cases, the highest beta1 integrin intensity score (3+ versus 0-2+) was associated with significantly decreased 10-year overall survival of 48% versus 71% (Pintegrin intensity score was significantly correlated with fibronectin expression (Kendall's tau-b=0.19; P=0.03). In a multivariate Cox proportional hazards model, beta1 integrin intensity score remained a significant independent predictor of overall survival [hazard ratio (HR), 1.69; 95% confidence interval (95% CI), 1.19-2.38; Pintegrin expression has potential prognostic value in invasive breast cancer and that coexpression of fibronectin may help identify patients with more aggressive tumors who may benefit from targeted therapy.

  14. Minimally Invasive Surgery for Intracochlear Schwannoma Removal and Simultaneous Cochlear Implantation

    Directory of Open Access Journals (Sweden)

    Bento, Ricardo Ferreira

    2016-04-01

    Full Text Available Introduction Hearing preservation has not yet been reported in patients undergoing resection of intracochlear schwannomas. This study describes a minimally invasive procedure for intracochlear schwannoma resection with simultaneous cochlear implantation that resulted in good hearing. Objective This study aims to describe a minimally invasive procedure for intracochlear schwannoma resection with simultaneous cochlear implantation. Data Synthesis The technique described in this study was developed for a 55-year-old male with a 20-year history of bilateral progressive hearing loss and tinnitus that had a mass in the left apical turn of the cochlea measuring 0.3 cm. Surgery accessed the apical turn of the cochlea. We performed mastoidectomy and posterior tympanotomy and removed incus and tensor tympani muscle to expose the cochlear apex. The tumor was identified and completely resected. After the cochlea was anatomically preserved, it was implanted with a straight electrode via round window insertion. The histopathological examination confirmed intracochlear schwannoma. Speech perception test revealed 100% speech recognition with closed sentences and the average audiometric threshold (500 to 2000 Hz was 23 dB. Conclusion Our technique led to rehabilitation of the patient and improved hearing without damaging the intracochlear structure, making it possible to perform CI in the same procedure with good results.

  15. The mathematics behind biological invasions

    CERN Document Server

    Lewis, Mark A; Potts, Jonathan R

    2016-01-01

    This book investigates the mathematical analysis of biological invasions. Unlike purely qualitative treatments of ecology, it draws on mathematical theory and methods, equipping the reader with sharp tools and rigorous methodology. Subjects include invasion dynamics, species interactions, population spread, long-distance dispersal, stochastic effects, risk analysis, and optimal responses to invaders. While based on the theory of dynamical systems, including partial differential equations and integrodifference equations, the book also draws on information theory, machine learning, Monte Carlo methods, optimal control, statistics, and stochastic processes. Applications to real biological invasions are included throughout. Ultimately, the book imparts a powerful principle: that by bringing ecology and mathematics together, researchers can uncover new understanding of, and effective response strategies to, biological invasions. It is suitable for graduate students and established researchers in mathematical ecolo...

  16. Cheatgrass invasion and wildlife habitat

    Science.gov (United States)

    The introduction and subsequent invasion of cheatgrass (Bromus tectorum) has altered native plant communities and the wildlife species that depend on these communities. Cheatgrass has truncated secondary succession by outcompeting native plant species for limited resources, thus building persistent...

  17. Invasive Meningococcal Men Y Disease

    Centers for Disease Control (CDC) Podcasts

    2012-04-18

    Dr. Leonard Mayer, a public health microbiologist at CDC, discusses invasive meningococcal disease.  Created: 4/18/2012 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 4/23/2012.

  18. Accidental introductions are an important source of invasive plants in the continental United States.

    Science.gov (United States)

    Lehan, Nora E; Murphy, Julia R; Thorburn, Lukas P; Bradley, Bethany A

    2013-07-01

    Preventing new plant invasions is critical for reducing large-scale ecological change. Most studies have focused on the deliberate introduction of nonnatives via the ornamental plant trade. However, accidental introduction may be an important source of nonnative, invasive plants. Using Web and literature searches, we compiled pathways of introduction to the United States for 1112 nonnative plants identified as invasive in the continental United States. We assessed how the proportion of accidentally and deliberately introduced invasive plants varies over time and space and by growth habit across the lower 48 states. Deliberate introductions of ornamentals are the primary source of invasive plants in the United States, but accidental introductions through seed contaminants are an important secondary source. Invasive forbs and grasses are the most likely to have arrived accidentally through seed contaminants, while almost all nonnative, invasive trees were introduced deliberately. Nonnative plants invading eastern states primarily arrived deliberately as ornamentals, while a high proportion of invasive plants in western states arrived accidentally as seed contaminants. Accidental introductions may be increasing in importance through time. Before 1850, 10 of 89 (11%) of invasive plants arrived accidentally. After 1900, 20 of 65 (31%) arrived accidentally. Recently enacted screening protocols and weed risk assessments aim to reduce the number of potentially invasive species arriving to the United States via deliberate introduction pathways. Increasing proportions of accidentally introduced invasive plants, particularly associated with contaminated seed imports across the western states, suggest that accidental introduction pathways also need to be considered in future regulatory decisions.

  19. Fatal invasive aspergillosis caused by Aspergillus niger after bilateral lung transplantation

    Directory of Open Access Journals (Sweden)

    Enora Atchade

    2017-09-01

    Full Text Available Aspergillus niger is usually considered to be a low virulence fungus, not commonly reported to cause invasive infections. Invasive pulmonary aspergillosis due to Aspergillus niger was diagnosed in a 43-year-old woman following bilateral lung transplantation. Intravenous voriconazole failed to control progression of the disease. Despite salvage therapy with a combination of voriconazole and caspofungin for 23 days, the patient developed massive hemoptysis leading to death. The authors report the clinical features and treatment of this case.

  20. Non-Invasive Prenatal Testing

    OpenAIRE

    Ekici, Cemal

    2015-01-01

    The rate of newborns with trisomy 21 (Down syndrome) who have been referred to our pediatric newborn clinic is very high. This shows that prenatal screening in the region is not carried out well. Prenatal diagnosis and screening methods include invasive prenatal diagnosis methods (amniocentesis, chorionic villus sampling (CVS), and cordocentesis) and non-invasive prenatal diagnosis (NIPT) which cell free fetal DNA (cffDNA) screening of maternal blood samples. After the discovery of the signs ...

  1. Non-Invasive Prenatal Testing

    OpenAIRE

    McGillivray, Barbara C.

    1988-01-01

    The rate of newborns with trisomy 21 (Down syndrome) who have been referred to our pediatric newborn clinic is very high. This shows that prenatal screening in the region is not carried out well. Prenatal diagnosis and screening methods include invasive prenatal diagnosis methods (amniocentesis, chorionic villus sampling (CVS), and cordocentesis) and non-invasive prenatal diagnosis (NIPT) which cell free fetal DNA (cffDNA) screening of maternal blood samples. After the discovery of the signs ...

  2. Quantifying the invasiveness of species

    Czech Academy of Sciences Publication Activity Database

    Colautti, R. I.; Parker, J. D.; Cadotte, M. W.; Pyšek, Petr; Brown, C. S.; Sax, D. F.; Richardson, D. M.

    2014-01-01

    Roč. 21, č. 1 (2014), s. 7-27 ISSN 1619-0033 R&D Projects: GA ČR(CZ) GAP505/11/1112; GA ČR(CZ) GAP504/11/1028 Grant - others:AV ČR(CZ) AP1002 Program:Akademická prémie - Praemium Academiae Institutional support: RVO:67985939 Keywords : biological invasions * biogeographical comparison * invasiveness Subject RIV: EH - Ecology, Behaviour

  3. Rapid loss of antipredatory behaviour in captive-bred birds is linked to current avian invasions

    OpenAIRE

    Carrete, Martina; Tella, Jos? L.

    2015-01-01

    Despite the importance of behaviour in conservation biology, there have been few studies that address behaviour in areas such as invasion ecology. There is an urgent need to identify specific traits that facilitate the establishment and spread of alien species to prevent biological invasions and their impact on biodiversity. Changes in antipredatory behaviour in captivity have been proposed to explain the higher invasiveness of wild-caught exotic species. We experimentally tested this hypothe...

  4. β1-Integrin via NF-κB signaling is essential for acquisition of invasiveness in a model of radiation treated in situ breast cancer.

    Science.gov (United States)

    Nam, Jin-Min; Ahmed, Kazi M; Costes, Sylvain; Zhang, Hui; Onodera, Yasuhito; Olshen, Adam B; Hatanaka, Kanako C; Kinoshita, Rumiko; Ishikawa, Masayori; Sabe, Hisataka; Shirato, Hiroki; Park, Catherine C

    2013-01-01

    Ductal carcinoma in situ (DCIS) is characterized by non-invasive cancerous cell growth within the breast ducts. Although radiotherapy is commonly used in the treatment of DCIS, the effect and molecular mechanism of ionizing radiation (IR) on DCIS are not well understood, and invasive recurrence following radiotherapy remains a significant clinical problem. This study investigated the effects of IR on a clinically relevant model of Akt-driven DCIS and identified possible molecular mechanisms underlying invasive progression in surviving cells. We measured the level of phosphorylated-Akt (p-Akt) in a cohort of human DCIS specimens by immunohistochemistry (IHC) and correlated it with recurrence risk. To model human DCIS, we used Akt overexpressing human mammary epithelial cells (MCF10A-Akt) which, in three-dimensional laminin-rich extracellular matrix (lrECM) and in vivo, form organotypic DCIS-like lesions with lumina expanded by pleiomorphic cells contained within an intact basement membrane. In a population of cells that survived significant IR doses in three-dimensional lrECM, a malignant phenotype emerged creating a model for invasive recurrence. P-Akt was up-regulated in clinical DCIS specimens and was associated with recurrent disease. MCF10A-Akt cells that formed DCIS-like structures in three-dimensional lrECM showed significant apoptosis after IR, preferentially in the luminal compartment. Strikingly, when cells that survived IR were repropagated in three-dimensional lrECM, a malignant phenotype emerged, characterized by invasive activity, up-regulation of fibronectin, α5β1-integrin, matrix metalloproteinase-9 (MMP-9) and loss of E-cadherin. In addition, IR induced nuclear translocation and binding of nuclear factor-kappa B (NF-κB) to the β1-integrin promoter region, associated with up-regulation of α5β1-integrins. Inhibition of NF-κB or β1-integrin signaling abrogated emergence of the invasive activity. P-Akt is up-regulated in some human DCIS lesions

  5. "Open" minimally invasive surgery in pediatric urology.

    Science.gov (United States)

    Hidalgo-Tamola, Josephine; Shnorhavorian, Margarett; Koyle, Martin A

    2009-06-01

    Minimally invasive surgery (MIS) offers alternative operative approaches to standard open surgical techniques. However, MIS has been defined primarily as substituting laparoendoscopic alternatives for the traditional open surgical approach. The concept of MIS methodology may also be applied to open surgery in an effort to decrease incision size, potentially reduce morbidity and enhance convalescence, without compromising 'gold standard' outcomes. Pediatric urological applications of open MIS include pediatric renal surgery, ureteral reimplantation, ureteral surgery, inguinal-scrotal and genital surgery. A thorough review of the pediatric urology literature was performed and studies were identified describing open MIS, including outcomes and complications.

  6. The role of the tissue microenvironment in the regulation of cancer cell motility and invasion

    Directory of Open Access Journals (Sweden)

    Brábek Jan

    2010-09-01

    Full Text Available Abstract During malignant neoplastic progression the cells undergo genetic and epigenetic cancer-specific alterations that finally lead to a loss of tissue homeostasis and restructuring of the microenvironment. The invasion of cancer cells through connective tissue is a crucial prerequisite for metastasis formation. Although cell invasion is foremost a mechanical process, cancer research has focused largely on gene regulation and signaling that underlie uncontrolled cell growth. More recently, the genes and signals involved in the invasion and transendothelial migration of cancer cells, such as the role of adhesion molecules and matrix degrading enzymes, have become the focus of research. In this review we discuss how the structural and biomechanical properties of extracellular matrix and surrounding cells such as endothelial cells influence cancer cell motility and invasion. We conclude that the microenvironment is a critical determinant of the migration strategy and the efficiency of cancer cell invasion.

  7. Plasminogen alleles influence susceptibility to invasive aspergillosis.

    Directory of Open Access Journals (Sweden)

    Aimee K Zaas

    2008-06-01

    Full Text Available Invasive aspergillosis (IA is a common and life-threatening infection in immunocompromised individuals. A number of environmental and epidemiologic risk factors for developing IA have been identified. However, genetic factors that affect risk for developing IA have not been clearly identified. We report that host genetic differences influence outcome following establishment of pulmonary aspergillosis in an exogenously immune suppressed mouse model. Computational haplotype-based genetic analysis indicated that genetic variation within the biologically plausible positional candidate gene plasminogen (Plg; Gene ID 18855 correlated with murine outcome. There was a single nonsynonymous coding change (Gly110Ser where the minor allele was found in all of the susceptible strains, but not in the resistant strains. A nonsynonymous single nucleotide polymorphism (Asp472Asn was also identified in the human homolog (PLG; Gene ID 5340. An association study within a cohort of 236 allogeneic hematopoietic stem cell transplant (HSCT recipients revealed that alleles at this SNP significantly affected the risk of developing IA after HSCT. Furthermore, we demonstrated that plasminogen directly binds to Aspergillus fumigatus. We propose that genetic variation within the plasminogen pathway influences the pathogenesis of this invasive fungal infection.

  8. [Primary progressive apraxia].

    Science.gov (United States)

    Kondo, Masaki

    2011-10-01

    Similar to primary progressive aphasia, primary progressive apraxia has been considered to cause slowly progressive apraxia without dementia and to be a dependent disease. Of the 3 cases reported by De Renzi in 1986, 1 case showed slowly progressive apraxia without dementia. Since then, cases of primary progressive apraxia have been reported occasionally. Studies on primary progressive apraxia indicate that not only focal lesions caused by vascular disease or brain trauma but also lesions caused by neurodegenerative disease can cause apraxia alone, thereby supporting the hypothesis that apraxia-associated neurodegeneration may develop in cases of primary progressive apraxia. The pathogenesis of primary progressive apraxia is yet to be elucidated. Clinical features of primary progressive apraxia are not precisely distinguishable from those of corticobasal degeneration (CBD); further, previous studies have indicated that the brain pathology observed in primary progressive apraxia is consistent with that in Alzheimer disease (AD) or Pick disease. "Primary" progressive apraxia may be intrinsically different from slowly progressive apraxia that is associated with CBD, AD, or Pick disease and may show specific pathological findings. On the other hand, primary progressive apraxia may not be a dependent disease but a syndrome characterized by prolonged neurodegeneration that is observed in various degenetive dementias such as CBD, AD, or Pick disease.

  9. The Culture of the Independent Progressive School

    Science.gov (United States)

    Kloss, Dean

    2018-01-01

    Even in this "Age of Data," independent progressive schools have shown a remarkable persistence in offering an alternative educational model. As Traditional Public Schools (TPS) become even more committed to a testing model of achievement, there are schools that continue to operate on identified progressive educational principles. This…

  10. Type I interferon protects against pneumococcal invasive disease by inhibiting bacterial transmigration across the lung.

    Directory of Open Access Journals (Sweden)

    Kim S LeMessurier

    Full Text Available Streptococcus pneumoniae infection is a leading cause of bacterial pneumonia, sepsis and meningitis and is associated with high morbidity and mortality. Type I interferon (IFN-I, whose contribution to antiviral and intracellular bacterial immunity is well established, is also elicited during pneumococcal infection, yet its functional significance is not well defined. Here, we show that IFN-I plays an important role in the host defense against pneumococci by counteracting the transmigration of bacteria from the lung to the blood. Mice that lack the type I interferon receptor (Ifnar1 (-/- or mice that were treated with a neutralizing antibody against the type I interferon receptor, exhibited enhanced development of bacteremia following intranasal pneumococcal infection, while maintaining comparable bacterial numbers in the lung. In turn, treatment of mice with IFNβ or IFN-I-inducing synthetic double stranded RNA (poly(I:C, dramatically reduced the development of bacteremia following intranasal infection with S. pneumoniae. IFNβ treatment led to upregulation of tight junction proteins and downregulation of the pneumococcal uptake receptor, platelet activating factor receptor (PAF receptor. In accordance with these findings, IFN-I reduced pneumococcal cell invasion and transmigration across epithelial and endothelial layers, and Ifnar1 (-/- mice showed overall enhanced lung permeability. As such, our data identify IFN-I as an important component of the host immune defense that regulates two possible mechanisms involved in pneumococcal invasion, i.e. PAF receptor-mediated transcytosis and tight junction-dependent pericellular migration, ultimately limiting progression from a site-restricted lung infection to invasive, lethal disease.

  11. Building a progressive vertical integration

    International Nuclear Information System (INIS)

    Charette, D.

    2008-01-01

    AAER Inc. is a Quebec-based company that manufactures turbines using proven European designs. This presentation discussed the company's business model. The company places an emphasis on identifying strategic and key components currently available for its turbines. Market analyses are performed in order to determine ideal suppliers and define business strategies and needs. The company invests in long-term relationships with its suppliers. Business partners for AAER are of a similar size and have a mutual understanding and respect for the company's business practices. Long-term agreements with suppliers are signed in order to ensure reliability and control over costs. Progressive vertical integration has been achieved by progressively manufacturing key components and integrating a North American supply chain. The company's secure supply chain and progressive vertical integration has significantly reduced financial costs and provided better quality control. It was concluded that vertical integration has also allowed AAER to provide better customer service and reduce transportation costs. tabs., figs

  12. Primary Progressive Aphasia

    Science.gov (United States)

    ... which cause different symptoms. Semantic variant primary progressive aphasia Symptoms include these difficulties: Comprehending spoken or written ... word meanings Naming objects Logopenic variant primary progressive aphasia Symptoms include: Having difficulty retrieving words Frequently pausing ...

  13. Progressive Pigmentary Purpura

    Science.gov (United States)

    ... Category: Share: Yes No, Keep Private Progressive Pigmentary Purpura Share | Progressive pigmentary purpura (we will call it PPP) is a group ... conditions ( Schamberg's disease , Lichenoid dermatitis of Gourgerot-Blum, purpura annularis telangiectodes of Majocchi and Lichen aureus). Schamberg's ...

  14. Progressive Supranuclear Palsy

    Science.gov (United States)

    ... alterations of mood and behavior, including depression and apathy as well as progressive mild dementia. The disorder's ... alterations of mood and behavior, including depression and apathy as well as progressive mild dementia. The disorder's ...

  15. Progress in K spectroscopy

    International Nuclear Information System (INIS)

    Leith, D.W.G.S.

    1977-07-01

    The progress in the field of K* spectroscopy is reviewed within the framework of the simple harmonic oscillator quark model, and contrasted with the recent progress made in the charmonium spectroscopy

  16. Progressive Multifocal Leukoencephalopathy

    Science.gov (United States)

    ... most prominent symptoms are clumsiness; progressive weakness; and visual, speech, and sometimes personality changes. The progression of deficits leads to life-threatening disability and (frequently) death. A diagnosis of PML can ...

  17. 75 FR 69698 - Invasive Species Advisory Committee

    Science.gov (United States)

    2010-11-15

    ... DEPARTMENT OF THE INTERIOR Office of the Secretary Invasive Species Advisory Committee AGENCY: Office of the Secretary, Interior. ACTION: Notice of public meetings of the Invasive Species Advisory... of meetings of the Invasive Species Advisory Committee (ISAC). Comprised of 30 nonfederal invasive...

  18. 76 FR 68776 - Invasive Species Advisory Committee

    Science.gov (United States)

    2011-11-07

    ... DEPARTMENT OF THE INTERIOR Office of the Secretary Invasive Species Advisory Committee AGENCY: Office of the Secretary, Interior. ACTION: Notice of public meetings of the Invasive Species Advisory... of meetings of the Invasive Species Advisory Committee (ISAC). Comprised of 29 nonfederal invasive...

  19. 77 FR 23740 - Invasive Species Advisory Committee

    Science.gov (United States)

    2012-04-20

    ... DEPARTMENT OF THE INTERIOR Office of the Secretary Invasive Species Advisory Committee AGENCY: Office of the Secretary, Interior. ACTION: Notice of Public Meetings of the Invasive Species Advisory... of meetings of the Invasive Species Advisory Committee (ISAC). Comprised of 30 nonfederal invasive...

  20. Predicting invasion in mammographically detected microcalcifcation: a preliminary report

    Directory of Open Access Journals (Sweden)

    Okugawa Homa

    2004-04-01

    Full Text Available Abstract Background With the increased use of mammography for breast cancer screening, the diagnosis of ductal carcinoma in situ (DCIS too has increased. This study was carried out to identify clinical and radiological factors that may predict the presence of invasive disease within mammographically detected microcalcifcation. Materials and methods A retrospective analysis of 13 vacuum-assisted breast biopsies (Mammotome® of mammographic calcification, which were reported to be either DCIS or invasive disease on final histopathology, was carried out. Final surgical pathology was correlated with pre-operative features (clinical, radiological and core histology to predict the presence of an invasive component. Results The overall sensitivity of Mammotome® was 81.8%, while for invasion it was 50%. Small size, granular morphology, increased number and area of calcification cluster may help in predicting invasion on mammography. Conclusions Mammotome® biopsy fails to detect invasion correctly in half the cases despite ascertaining correctness of biopsy with post biopsy x-ray.

  1. White matter lesion progression

    DEFF Research Database (Denmark)

    Hofer, Edith; Cavalieri, Margherita; Bis, Joshua C

    2015-01-01

    BACKGROUND AND PURPOSE: White matter lesion (WML) progression on magnetic resonance imaging is related to cognitive decline and stroke, but its determinants besides baseline WML burden are largely unknown. Here, we estimated heritability of WML progression, and sought common genetic variants...... and previous association studies. RESULTS: A total of 1085 subjects showed WML progression. The heritability estimate for WML progression was low at 6.5%, and no single-nucleotide polymorphisms achieved genome-wide significance (PFour loci were suggestive (P

  2. Downregulation of NEDD9 by apigenin suppresses migration, invasion, and metastasis of colorectal cancer cells

    International Nuclear Information System (INIS)

    Dai, Jin; Van Wie, Peter G.; Fai, Leonard Yenwong; Kim, Donghern; Wang, Lei; Poyil, Pratheeshkumar; Luo, Jia; Zhang, Zhuo

    2016-01-01

    Apigenin is a natural flavonoid which possesses multiple anti-cancer properties such as anti-proliferation, anti-inflammation, and anti-metastasis in many types of cancers including colorectal cancer. Neural precursor cell expressed developmentally downregulated 9 (NEDD9) is a multi-domain scaffolding protein of the Cas family which has been shown to correlate with cancer metastasis and progression. The present study investigates the role of NEDD9 in apigenin-inhibited cell migration, invasion, and metastasis of colorectal adenocarcinoma DLD1 and SW480 cells. The results show that knockdown of NEDD9 inhibited cell migration, invasion, and metastasis and that overexpression of NEDD9 promoted cell migration and invasion of DLD1 cells and SW4890 cells. Apigenin treatment attenuated NEDD9 expression at protein level, resulting in reduced phosphorylations of FAK, Src, and Akt, leading to inhibition on cell migration, invasion, and metastasis of both DLD1 and SW480 cells. The present study has demonstrated that apigenin inhibits cell migration, invasion, and metastasis through NEDD9/Src/Akt cascade in colorectal cancer cells. NEDD9 may function as a biomarker for evaluation of cancer aggressiveness and for selection of therapeutic drugs against cancer progression. - Highlights: • Apigenin inhibits migration, invasion, and metastasis of colorectal cancer cells. • Apigenin downregulates NEDD9. • Apigenin decreases phosphorylations of FAK, Src, and Akt. • Apigenin inhibits cell migration, invasion, and metastasis through NEDD9/Src/Akt.

  3. A new non-invasive approach based on polyhexamethylene biguanide increases the regression rate of HPV infection

    Directory of Open Access Journals (Sweden)

    Gentile Antonio

    2012-09-01

    Full Text Available Abstract Background HPV infection is a worldwide problem strictly linked to the development of cervical cancer. Persistence of the infection is one of the main factors responsible for the invasive progression and women diagnosed with intraepithelial squamous lesions are referred for further assessment and surgical treatments which are prone to complications. Despite this, there are several reports on the spontaneous regression of the infection. This study was carried out to evaluate the effectiveness of a long term polyhexamethylene biguanide (PHMB-based local treatment in improving the viral clearance, reducing the time exposure to the infection and avoiding the complications associated with the invasive treatments currently available. Method 100 women diagnosed with HPV infection were randomly assigned to receive six months of treatment with a PHMB-based gynecological solution (Monogin®, Lo.Li. Pharma, Rome - Italy or to remain untreated for the same period of time. Results A greater number of patients, who received the treatment were cleared of the infection at the two time points of the study (three and six months compared to that of the control group. A significant difference in the regression rate (90% Monogin group vs 70% control group was observed at the end of the study highlighting the time-dependent ability of PHMB to interact with the infection progression. Conclusions The topic treatment with PHMB is a preliminary safe and promising approach for patients with detected HPV infection increasing the chance of clearance and avoiding the use of invasive treatments when not strictly necessary. Trial registration ClinicalTrials.gov Identifier NCT01571141

  4. Clinical Investigation Program Annual Progress Report

    Science.gov (United States)

    1993-09-30

    Assisted Cell Sorting (FACS). Data collection is in progress. CPS successfully identified antibody titers for bullous pemphigoid and pemphigus vulgaris ...Status: Completed (4) Title: Determination of Indirect Immunofluorescence Results in Bullous Pemphigoid and Pemphigus (5) Start Date: 1992 (6) Est

  5. Progress report. June to Sept 1975 (1)

    International Nuclear Information System (INIS)

    1975-10-01

    History of the Nuclear Research Centre (NRC) showing objectives and progress during the three month period June to September 1975. Each section is identified within the NRC and its individual activities are defined

  6. MicroRNA-197 inhibits gastric cancer progression by directly targeting metadherin.

    Science.gov (United States)

    Liao, Zhiwei; Li, Yue; Zhou, Yuanhang; Huang, Qi; Dong, Jian

    2018-01-01

    Gastric cancer is the fifth most frequent malignancy and the fourth most common cause of cancer‑associated mortality worldwide. MicroRNAs (miRNAs) are a group of small RNAs that regulate several cellular processes. In particular, a large number of miRNAs are involved in gastric cancer formation and progression. Thus, miRNAs may be considered as effective diagnostic biomarkers and therapeutic methods for gastric cancer. The aim of the current study was to detect miRNA (miR)‑197 expression in gastric cancer and to investigate its biological role and associated mechanism in gastric cancer. In the present study, miR‑197 expression was demonstrated to be considerably downregulated in gastric cancer tissues and cell lines. Its low expression level was associated with tumour size, invasive depth, tumour‑node‑metastasis staging and lymph node metastasis. High expression of miR‑197 inhibited tumour cell proliferation and invasion in vitro. Subsequently, metadherin (MTDH) was identified as a direct target gene of miR‑197 in gastric cancer, and this was confirmed by bioinformatics analysis, Dual‑luciferase reporter assay, reverse transcription quantitative polymerase chain reaction and western blot analysis. MTDH expression was upregulated in gastric cancer and was inversely correlated with miR‑197 expression levels. In addition, MTDH overexpression prevented the proliferation and inhibited invasion induced by miR‑197 overexpression. In addition, miR‑197 was demonstrated to regulate the phosphatase and tensin homolog (PTEN)/AKT signalling pathway in gastric cancer. The results of the present study suggested that miR‑197 serves a tumour‑suppressing role in human gastric carcinogenesis and progression by regulating the MTDH/PTEN/AKT signalling pathway. The miR‑197/MTDH axis may provide a novel effective therapeutic target for patients with gastric cancer.

  7. Bladder cancer: utility of MRI in detection of occult muscle-invasive disease

    International Nuclear Information System (INIS)

    Rosenkrantz, Andrew B.; Mussi, Thais C.; Melamed, Jonathan; Taneja, Samir S.; Huang, William C.

    2012-01-01

    Background. The presence of muscularis propria invasion by bladder cancer is a key factor in prognosis and treatment decisions, although may be missed by biopsy due to sampling error. MRI has shown potential for detection of muscle invasion but has not specifically been evaluated for this purpose in the setting of bladder cancer patients without evidence of muscle invasion on initial biopsy. Purpose. To evaluate the role of MRI in detection of muscularis propria invasion by bladder cancer following a pathologic diagnosis of non-invasive tumor. Material and Methods. This retrospective study included 23 patients who underwent pelvic MRI following a pathologic diagnosis of bladder cancer without muscularis propria invasion and in whom additional histologic evaluation was performed following MRI. Two radiologists in consensus reviewed T2-weighted images to identify those cases suspicious for muscle invasion on MRI. The radiologists identified whether cases suspicious for invasion demonstrated disruption of the T2-hypointense muscularis layer of the bladder wall, peri-vesical fat stranding, and peri-vesical soft tissue nodularity. Findings were compared with pathologic results obtained after MRI. Results. Suspicion was raised for muscle invasion in eight of 23 cases, four of which exhibited invasion on follow-up pathology. No case without suspicion on MRI exhibited invasion on follow-up pathology. Therefore, sensitivity and specificity were 100% and 79%, respectively. Among individual findings, muscularis disruption on T2WI exhibited sensitivity of 100% and specificity of 79%, peri-vesical fat stranding exhibited sensitivity and specificity of 50% and 84%, and peri-vesical soft tissue nodularity exhibited sensitivity and specificity of 25% and 100%. Conclusion. MRI demonstrated high sensitivity for detection of muscle invasion in cases of bladder cancer without invasion on initial histologic assessment. Muscularis disruption on T2WI appeared to exhibit a better

  8. Bladder cancer: utility of MRI in detection of occult muscle-invasive disease

    Energy Technology Data Exchange (ETDEWEB)

    Rosenkrantz, Andrew B. [Dept. of Radiology, NYU Langone Medical Center, New York (United States)], E-mail: Andrew.rosenkrantz@nyumc.org; Mussi, Thais C. [Dept. of Radiology, NYU Langone Medical Center, New York (United States); Hospital Israelita Albert Einstein, Sao Paulo (Brazil); Melamed, Jonathan [Dept. of Pathology, NYU Langone Medical Center, New York (United States); Taneja, Samir S.; Huang, William C. [Dept. of Urology, Div. of Urologic Oncology, NYU Langone Medical Center, New York (United States)

    2012-07-15

    Background. The presence of muscularis propria invasion by bladder cancer is a key factor in prognosis and treatment decisions, although may be missed by biopsy due to sampling error. MRI has shown potential for detection of muscle invasion but has not specifically been evaluated for this purpose in the setting of bladder cancer patients without evidence of muscle invasion on initial biopsy. Purpose. To evaluate the role of MRI in detection of muscularis propria invasion by bladder cancer following a pathologic diagnosis of non-invasive tumor. Material and Methods. This retrospective study included 23 patients who underwent pelvic MRI following a pathologic diagnosis of bladder cancer without muscularis propria invasion and in whom additional histologic evaluation was performed following MRI. Two radiologists in consensus reviewed T2-weighted images to identify those cases suspicious for muscle invasion on MRI. The radiologists identified whether cases suspicious for invasion demonstrated disruption of the T2-hypointense muscularis layer of the bladder wall, peri-vesical fat stranding, and peri-vesical soft tissue nodularity. Findings were compared with pathologic results obtained after MRI. Results. Suspicion was raised for muscle invasion in eight of 23 cases, four of which exhibited invasion on follow-up pathology. No case without suspicion on MRI exhibited invasion on follow-up pathology. Therefore, sensitivity and specificity were 100% and 79%, respectively. Among individual findings, muscularis disruption on T2WI exhibited sensitivity of 100% and specificity of 79%, peri-vesical fat stranding exhibited sensitivity and specificity of 50% and 84%, and peri-vesical soft tissue nodularity exhibited sensitivity and specificity of 25% and 100%. Conclusion. MRI demonstrated high sensitivity for detection of muscle invasion in cases of bladder cancer without invasion on initial histologic assessment. Muscularis disruption on T2WI appeared to exhibit a better

  9. Identificación de los mecanismos subyacentes a la invasión de Castor canadensis (Rodentia en el archipiélago de Tierra del Fuego, Chile Identifying the mechanisms underlying the invasion of Castor canadensis (Rodentia into Tierra del Fuego archipelago, Chile

    Directory of Open Access Journals (Sweden)

    PETRA K WALLEM

    2007-09-01

    conceptual sobre el cual se pueden desarrollar futuras investigaciones referentes a esta invasiónCastor canadensis is considered an archetypical ecosystem engineer, which modifies the state of biotic and abiotic factors through non-trophic interactions. This species was introduced by the Argentinean government into Tierra del Fuego island in 1946, and subsequently colonized autonomously the neighboring islands of Navarino, Dawson and Hoste. Currently this invader occupies contrasting ecosystems such as the Magellan subpolar beech forest and Patagonian scrub and steppe. This ability to colonize contrasting habitats suggests that beaver expansion will be limited mainly by hydrological resources, threatening to colonize the complete extent of temperate beech forests on the mainland (from 35 to 55° S. The present review proposes three hypotheses regarding the underlying mechanisms to this successful invasion: natural enemy escape, resource opportunities, and self-facilitation through non-trophic interactions. Current knowledge regarding beaver colonization and foraging behavior (e.g., habitat selection independently of forest availability, irruptive population growth, and apparent selective exploitation of Nothofagus pumilio, dominant species in the Magellan forest suggests that enemy escape and resource opportunity are the main mechanisms underlying this invasion. The observation of higher densities of active colonies, where the extent of beaver habitat modification is larger, suggests that self-facilitation may be relevant to the success of this invasion. Current information does not allow testing these hypotheses, but it provides a framework to develop future investigations regarding this invasion in Tierra del Fuego

  10. Functional characterization of the transcription factor ZEB1 in epithelial to mesenchymal transition and cancer progression

    International Nuclear Information System (INIS)

    Sultan, A.

    2010-01-01

    Epithelial to mesenchymal transition (EMT) is implicated in the progression of primary tumours towards metastasis and is likely caused by a pathological activation of transcription factors regulating EMT in embryonic development. To analyse EMT-causing pathways in tumourigenesis, transcriptional targets of the E-cadherin repressor ZEB1 in invasive humancancer cells were identified. We show that ZEB1 repressed multiple key determinants of epithelial differentiation and cell-cell adhesion, including the cell polarity genes Crumbs3, HUGL2, PKP3 and Pals1-associated tight junction protein. ZEB1 associated with their endogenous promoters in vivo, and strongly repressed promoter activities in reporter assays. ZEB1 downregulation in undifferentiated cancer cells by RNA interference was sufficient to upregulate expression of these cell polarity genes on the RNA and protein level, to re-establish epithelial features and to impair cell motility in vitro. In human colorectal cancer, ZEB1 expression was limited to the tumour-host interface and was accompanied by loss of intercellular adhesion and tumour cell invasion. EMT-inducing transcriptional repressor ZEB1 promotes colorectal cancer cell metastasis and loss of cell polarity. Thereby, ZEB1 suppresses the expression of cell polarity factors, in particular of Lgl2, which was found to be reduced in colorectal and breast cancers. In invasive ductal and lobular breast cancer, upregulation of ZEB1 was stringently coupled to cancer cell dedifferentiation. The invasion potential of MDA-MB-231, a highly invasive breast cancer cell line, is shown to be under the control of ZEB1. Over-expression of ZEB1downregulates and relocalizes E-Cadherin in MCF7 breast cancer cells; moreover, ZEB1 overexpression results in reduced proliferation rate of these cells. Most importantly, we show that ZEB1 mediated downregulation of E-cadherin involves chromatin modifications. Markers of transcriptionally active chromatin Acetylated H3 and Acetylated

  11. Proteomic analysis of skin invasion by blood fluke larvae.

    Directory of Open Access Journals (Sweden)

    Elizabeth Hansell

    2008-07-01

    Full Text Available During invasion of human skin by schistosome blood fluke larvae (cercariae, a multicellular organism breaches the epidermis, basement membrane, and dermal barriers of skin. To better understand the pathobiology of this initial event in schistosome infection, a proteome analysis of human skin was carried out following invasion by cercariae of Schistosoma mansoni.Human skin samples were exposed to cercariae for one-half hour to two hours. Controls were exposed to water used to collect cercariae in an identical manner, and punctured to simulate cercarial tunnels. Fluid from both control and experimental samples was analyzed by LC/MS/MS using a linear ion trap in "triple play" mode. The coexistence of proteins released by cercariae and host skin proteins from epidermis and basement membrane confirmed that cercarial tunnels in skin were sampled. Among the abundant proteins secreted by cercariae was the cercarial protease that has been implicated in degradation of host proteins, secreted proteins proposed to mediate immune invasion by larvae, and proteins implicated in protection of parasites against oxidative stress. Components of the schistosome surface tegument, previously identified with immune serum, were also released. Both lysis and apoptosis of epidermal cells took place during cercarial invasion of the epidermis. Components of lysed epidermal cells, including desmosome proteins which link cells in the stratum granulosum and stratum spinosum, were identified. While macrophage-derived proteins were present, no mast cell or lymphocyte cytokines were identified. There were, however, abundant immunoglobulins, complement factors, and serine protease inhibitors in skin. Control skin samples incubated with water for the same period as experimental samples ensured that invasion-related proteins and host protein fragments were not due to nonspecific degeneration of the skin samples.This analysis identified secreted proteins from invasive larvae that

  12. High expression of WISP1 in colon cancer is associated with apoptosis, invasion and poor prognosis.

    Science.gov (United States)

    Wu, Jianghong; Long, Ziwen; Cai, Hong; Du, Chunyan; Liu, Xiaowen; Yu, Shengjia; Wang, Yanong

    2016-08-02

    Colon cancer (CC) likes many epithelial-derived cancers, resulting from a complex tumorigenic process. However, the exactly mechanisms of development and progression of CC are still unknown. In this study, integrated analysis in the GSE33113 and Fudan University Shanghai Cancer Center Hospital datasets revealed that WISP1 expression was significantly increased in CC cases, positivity correlated with the advanced pathologic stage and a poor prognosis was more likely in CC patients with higher levels of WISP1. Downregulation of WISP1 inhibited cell proliferation and invasion through increasing apoptosis and blocking cell cycle at G1 phase in CC LOVO and RKO cells. Besides, Gene set enrichment analysis (GSEA) revealed that relative genes involved in the Cell adhesion molecules and Cytokine-cytokine receptor interaction pathways were enriched in WISP1-higher expression patients. Western blot analysis showed that Cell adhesion molecules pathway associated genes (ICAM- 1, VCAM-1, SDC2 and CDH2) and Cytokine-cytokine receptor interaction pathway associated genes (VEGFC, CCL18, CXCR4 and TGFBR1) were also modulated by WISP1 downregulation. Then, we found that the protein β-catenin was identified as a binding partner of WISP1 and mediated the functions of WISP1 through promoting cell proliferation and invasion in LOVO and RKO cells. Further in vivo tumor formation study in nude mice indicated that inhibition of WISP1 delayed the progress of tumor formation and inhibited PCNA expression. These results indicate that WISP1 could act as an oncogene and may serve as a promising therapeutic strategy for colon cancer.

  13. New target genes of MITF-induced microRNA-211 contribute to melanoma cell invasion.

    Directory of Open Access Journals (Sweden)

    Christiane Margue

    Full Text Available The non-coding microRNAs (miRNA have tissue- and disease-specific expression patterns. They down-regulate target mRNAs, which likely impacts on most fundamental cellular processes. Differential expression patterns of miRNAs are currently being exploited for identification of biomarkers for early disease diagnosis, prediction of progression for melanoma and other cancers and as promising drug targets, since they can easily be inhibited or replaced in a given cellular context. Before successfully manipulating miRNAs in clinical settings, their precise expression levels, endogenous functions and thus their target genes have to be determined. MiR-211, a melanocyte lineage-specific small non-coding miRNA, is located in an intron of TRPM1, a target gene of the microphtalmia-associated transcription factor (MITF. By transcriptionally up-regulating TRPM1, MITF, which is critical for both melanocyte differentiation and survival and for melanoma progression, indirectly drives the expression of miR-211. Expression of this miRNA is often reduced in melanoma samples. Here, we investigated functional roles of miR-211 by identifying and studying new target genes. We show that MITF-correlated miR-211 expression levels are mostly but not always reduced in a panel of 11 melanoma cell lines and in primary and metastatic melanoma compared to normal melanocytes and nevi, respectively. MiR-211 itself only marginally impacted on cell invasion and migration, while perturbation of some new miR-211 target genes, such as AP1S2, SOX11, IGFBP5, and SERINC3 significantly increased invasion. These results and the variable expression levels of miR-211 raise serious doubts on the value of miR-211 as a melanoma tumor-suppressing miRNA and/or as a biomarker for melanoma.

  14. Collagen reorganization at the tumor-stromal interface facilitates local invasion

    Directory of Open Access Journals (Sweden)

    Inman David R

    2006-12-01

    Full Text Available Abstract Background Stromal-epithelial interactions are of particular significance in breast tissue as misregulation of these interactions can promote tumorigenesis and invasion. Moreover, collagen-dense breast tissue increases the risk of breast carcinoma, although the relationship between collagen density and tumorigenesis is not well understood. As little is known about epithelial-stromal interactions in vivo, it is necessary to visualize the stroma surrounding normal epithelium and mammary tumors in intact tissues to better understand how matrix organization, density, and composition affect tumor formation and progression. Methods Epithelial-stromal interactions in normal mammary glands, mammary tumors, and tumor explants in three-dimensional culture were studied with histology, electron microscopy, and nonlinear optical imaging methodologies. Imaging of the tumor-stromal interface in live tumor tissue ex vivo was performed with multiphoton laser-scanning microscopy (MPLSM to generate multiphoton excitation (MPE of endogenous fluorophores and second harmonic generation (SHG to image stromal collagen. Results We used both laser-scanning multiphoton and second harmonic generation microscopy to determine the organization of specific collagen structures around ducts and tumors in intact, unfixed and unsectioned mammary glands. Local alterations in collagen density were clearly seen, allowing us to obtain three-dimensional information regarding the organization of the mammary stroma, such as radiating collagen fibers that could not have been obtained using classical histological techniques. Moreover, we observed and defined three tumor-associated collagen signatures (TACS that provide novel markers to locate and characterize tumors. In particular, local cell invasion was found predominantly to be oriented along certain aligned collagen fibers, suggesting that radial alignment of collagen fibers relative to tumors facilitates invasion. Consistent

  15. Tiam1 transgenic mice display increased tumor invasive and metastatic potential of colorectal cancer after 1,2-dimethylhydrazine treatment.

    Science.gov (United States)

    Yu, Li-Na; Zhang, Qing-Ling; Li, Xin; Hua, Xing; Cui, Yan-Mei; Zhang, Nian-Jie; Liao, Wen-Ting; Ding, Yan-Qing

    2013-01-01

    T lymphoma invasion and metastasis 1 (Tiam1) is a potential modifier of tumor development and progression. Our previous study in vitro and in nude mice suggested a promotion role of Tiam1 on invasion and metastasis of colorectal cancer (CRC). In the present study, we generated Tiam1/C1199-CopGFP transgenic mice to investigate the tumorigenetic, invasive and metastatic alterations in the colon and rectum of wild-type and Tiam1 transgenic mice under 1,2-dimethylhydrazine (DMH) treatment. Transgenic mice were produced by the method of pronuclear microinlectlon. Whole-body fluorescence imaging (Lighttools, Edmonton, Alberta, Canada), PCR, and immunohistochemical techniques (IHC) were applied sequentially to identify the transgenic mice. The carcinogen DMH (20 mg/kg) was used to induce colorectal tumors though intraperitoneal (i.p.) injections once a week for 24 weeks from the age of 4 weeks on Tiam1 transgenic or non-transgenic mice. We successfully generated Tiam1/C1199-CopGFP transgenic mice and induced primary tumors in the intestine of both wild type and Tiam1 transgenic mice by DMH treatment. In addition, Tiam1 transgenic mice developed larger and more aggressive neoplasm than wild-type mice. Moreover, immunohistochemical staining revealed that upregulation of Tiam1 was correlated with increased expression of β-Catenin and Vimentin, and downregulation of E-Cadherin in these mice. Our study has provided in vivo evidence supporting that Tiam1 promotes invasion and metastasis of CRC, most probably through activation of Wnt/β-catenin signaling pathway, in a Tiam1 transgenic mouse model.

  16. Proanthocyanidin in red rice inhibits MDA-MB-231 breast cancer cell invasion via the expression control of invasive proteins.

    Science.gov (United States)

    Pintha, Komsak; Yodkeeree, Supachai; Limtrakul, Pornngarm

    2015-01-01

    Proanthocyanidin is one of the main active compounds found in red jasmine rice. We previously reported that red rice extract could reduce cancer cell invasion. However, the direct effect of proanthocyanidin from red rice on the invasion of cancer cells and the exact molecular mechanism remained unclear. Here, we report for the first time that proanthocyanidin-rich fraction from red rice (PRFR) reduced the migration and invasion of MDA-MB-231 human breast cancer cells. The types of proanthocyanidin in PRFR were identified as procyanidins and prodelphinidins by acid hydrolysis. For cancer cell invasion, degradation of the extracellular matrix (ECM) is required. Treatment of the cells with PRFR reduced the expression of ECM degradation-associated proteins, including matrix metalloproteinase-9 (MMP-9), membrane type-1 matrix metalloproteinase, urokinase plasminogen activator, urokinase plasminogen activator receptor and plasminogen activator-1. Moreover, PRFR also reduced the activity of collagenase and MMP-9. Furthermore, PRFR significantly suppressed the expression of intercellular adhesion molecule-1 and interleukin-6. We also found that PRFR reduced the DNA-binding activity of nuclear factor kappa B (NF-κB), which is the expressed mediator of ECM degradation-associated proteins. These results suggest that proanthocyanidin from red rice mediates MDA-MB-231 breast cancer cell invasion by altering the expression of the invasion-associated proteins, possibly by targeting NF-κB activity.

  17. Invasive amphibians in southern Africa: A review of invasion pathways

    Directory of Open Access Journals (Sweden)

    John Measey

    2017-03-01

    Full Text Available Background: Globally, invasive amphibians are known for their environmental and social impacts that range from poisoning of local fauna and human populations to direct predation on other amphibians. Although several countries on most continents have had multiple introductions of many species, southern Africa appears to have escaped allochthonous introductions. Instead, it has a small number of domestic exotic species that have rapidly expanded their ranges and established invasive populations within South Africa. Objectives & methods: We used the literature to provide a historical overview of dispersal by some of the world’s major invasive amphibians, give examples of species that are commonly moved as stowaways and discuss historical and current amphibian trade in the region. In addition, we give an overview of new South African legislation and how this is applied to amphibian invasions, as well as providing updates on the introduced populations of three domestic exotics: Hyperolius marmoratus, Sclerophrys gutturalis and Xenopus laevis. Results: We show that frogs are mainly moved around southern Africa through ‘jump’ dispersal, although there are a number of records of ‘cultivation’, ‘leading-edge’ and ‘extreme long-distance’ dispersal types. Important pathways include trade in fruit and vegetables, horticultural products and shipping containers. Conclusion: We suggest that southern Africa is becoming more vulnerable to amphibian invasions because of an increase in trade, agricultural and domestic impoundments as well as global climate change. Increasing propagule pressure suggests that preventing new introductions will become a key challenge for the future. Currently, trade in amphibians in the region is practically non-existent, suggesting potential for best practice to prevent importation of species with high invasion potential and to stop the spread of disease.

  18. Predicting Progression from Mild Cognitive Impairment to Alzheimer's Dementia Using Clinical, MRI, and Plasma Biomarkers via Probabilistic Pattern Classification

    Science.gov (United States)

    Korolev, Igor O.; Symonds, Laura L.; Bozoki, Andrea C.

    2016-01-01

    MCI-to-dementia progression over a three-year period. The model utilizes widely available, cost-effective, non-invasive markers and can be used to improve patient selection in clinical trials and identify high-risk MCI patients for early treatment. PMID:26901338

  19. Predicting Progression from Mild Cognitive Impairment to Alzheimer's Dementia Using Clinical, MRI, and Plasma Biomarkers via Probabilistic Pattern Classification.

    Directory of Open Access Journals (Sweden)

    Igor O Korolev

    over a three-year period. The model utilizes widely available, cost-effective, non-invasive markers and can be used to improve patient selection in clinical trials and identify high-risk MCI patients for early treatment.

  20. Progressive Supranuclear Palsy: an Update.

    Science.gov (United States)

    Armstrong, Melissa J

    2018-02-17

    Progressive supranuclear palsy (PSP) is a 4R tau neuropathologic entity. While historically defined by the presence of a vertical supranuclear gaze palsy and falls in the first symptomatic year, clinicopathologic studies identify alternate presenting phenotypes. This article reviews the new PSP diagnostic criteria, diagnostic approaches, and treatment strategies. The 2017 International Parkinson and Movement Disorder Society PSP criteria outline 14 core clinical features and 4 clinical clues that combine to diagnose one of eight PSP phenotypes with probable, possible, or suggestive certainty. Evidence supports the use of select imaging approaches in the classic PSP-Richardson syndrome phenotype. Recent trials of putative disease-modifying agents showed no benefit. The new PSP diagnostic criteria incorporating the range of presenting phenotypes have important implications for diagnosis and research. More work is needed to understand how diagnostic evaluations inform phenotype assessment and identify expected progression. Current treatment is symptomatic, but tau-based therapeutics are in active clinical trials.

  1. Anesthesia for minimally invasive neurosurgery.

    Science.gov (United States)

    Prabhakar, Hemanshu; Mahajan, Charu; Kapoor, Indu

    2017-10-01

    With an ultimate aim of improving patients overall outcome and satisfaction, minimally invasive surgical approach is becoming more of a norm. The related anesthetic evidence has not expanded at the same rate as surgical and technological advancement. This article reviews the recent evidence on anesthesia and perioperative concerns for patients undergoing minimally invasive neurosurgery. Minimally invasive cranial and spinal surgeries have been made possible only by vast technological development. Points of surgical interest can be precisely located with the help of stereotaxy and neuronavigation and special endoscopes which decrease the tissue trauma. The principles of neuroanethesia remain the same, but few concerns are specific for each technique. Dexmedetomidine has a favorable profile for procedures carried out under sedation technique. As the new surgical techniques are coming up, lesser known anesthetic concerns may also come into light. Over the last year, little new information has been added to existing literature regarding anesthesia for minimally invasive neurosurgeries. Neuroanesthesia goals remain the same and less invasive surgical techniques do not translate into safe anesthesia. Specific concerns for each procedure should be taken into consideration.

  2. Interstitial guidance of cancer invasion.

    Science.gov (United States)

    Gritsenko, Pavlo G; Ilina, Olga; Friedl, Peter

    2012-01-01

    Cancer cell invasion into healthy tissues develops preferentially along pre-existing tracks of least resistance, followed by secondary tissue remodelling and destruction. The tissue scaffolds supporting or preventing guidance of invasion vary in structure and molecular composition between organs. In the brain, the guidance is provided by myelinated axons, astrocyte processes, and blood vessels which are used as invasion routes by glioma cells. In the human breast, containing interstitial collagen-rich connective tissue, disseminating breast cancer cells preferentially invade along bundled collagen fibrils and the surface of adipocytes. In both invasion types, physical guidance prompted by interfaces and space is complemented by molecular guidance. Generic mechanisms shared by most, if not all, tissues include (i) guidance by integrins towards fibrillar interstitial collagen and/or laminins and type IV collagen in basement membranes decorating vessels and adipocytes, and, likely, CD44 engaging with hyaluronan; (ii) haptotactic guidance by chemokines and growth factors; and likely (iii) physical pushing mechanisms. Tissue-specific, resticted guidance cues include ECM proteins with restricted expression (tenascins, lecticans), cell-cell interfaces, and newly secreted matrix molecules decorating ECM fibres (laminin-332, thrombospondin-1, osteopontin, periostin). We here review physical and molecular guidance mechanisms in interstitial tissue and brain parenchyma and explore shared principles and organ-specific differences, and their implications for experimental model design and therapeutic targeting of tumour cell invasion. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  3. Distribution, density and impact of invasive plants in Lake Nakuru National Park, Kenya

    NARCIS (Netherlands)

    Ngweno, C.C.; Mwasi, S.M.; Kairu, J.K.

    2010-01-01

    Invasive plants have invaded swathes of grasslands in Lake Nakuru National Park thus necessitating the Park management to institute measures to control them. Despite this, information on the status and impact of invasive plants in these grasslands is lacking. Six grassland types were identified and

  4. Chapter 12: Gaps in scientific knowledge about fire and nonnative invasive plants

    Science.gov (United States)

    Kristin Zouhar; Gregory T. Munger; Jane Kapler Smith

    2008-01-01

    The potential for nonnative, invasive plants to alter an ecosystem depends on species traits, ecosystem characteristics, and the effects of disturbances, including fire. This study identifies gaps in science-based knowledge about the relationships between fire and nonnative invasive plants in the United States. The literature was searched for information on 60...

  5. Advanced signal processing theory and implementation for sonar, radar, and non-invasive medical diagnostic systems

    CERN Document Server

    Stergiopoulos, Stergios

    2009-01-01

    Integrates topics of signal processing from sonar, radar, and medical system technologies by identifying their concept similarities. This book covers non-invasive medical diagnostic system applications, including intracranial ultrasound, a technology that attempts to address non-invasive detection on brain injuries and stroke.

  6. Blue-light cystoscopy in the evaluation of non-muscle-invasive bladder cancer

    NARCIS (Netherlands)

    Oude Elferink, P.; Witjes, J.A.

    2014-01-01

    Bladder carcinoma is the most common malignancy of the urinary tract. Two distinct groups can be identified: non-muscle-invasive bladder carcinoma (NMIBC) and muscle-invasive bladder carcinoma. At initial resection about 75-85% of the patients will be diagnosed with NMIBC. This subgroup has a

  7. Fire and simulated herbivory have antagonistic effects on resistance of savanna grasslands to alien shrub invasion

    NARCIS (Netherlands)

    te Beest, Mariska; Mpandza, Nokukhanya J.; Olff, Han

    Question Resistance of the native community has been identified as an important factor limiting invasion success and invader impact. However, to what extent resistance interacts with disturbance to control invasion success remains unclear. We studied the interaction between biotic resistance, fire

  8. Bone marrow-derived mesenchymal stem cells promote colorectal cancer progression through paracrine neuregulin 1/HER3 signalling.

    Science.gov (United States)

    De Boeck, Astrid; Pauwels, Patrick; Hensen, Karen; Rummens, Jean-Luc; Westbroek, Wendy; Hendrix, An; Maynard, Dawn; Denys, Hannelore; Lambein, Kathleen; Braems, Geert; Gespach, Christian; Bracke, Marc; De Wever, Olivier

    2013-04-01

    Bone marrow-derived mesenchymal stem cells (BM-MSC) migrate to primary tumours and drive tumour progression. This study aimed to identify the molecular mechanisms associated with these heterotypic cellular interactions and analyse their relevance in colorectal cancer (CRC). Paracrine interactions of BM-MSC with CRC cells were studied using collagen invasion assays, cell counts, flow cytometric cell-cycle analysis and tumour xenograft models. The role of neuregulin 1 (NRG1) and the human epidermal growth factor receptor (HER) family pathways were investigated using tyrosine kinase assays, mass spectrometry, pharmacological inhibition, antibody-mediated neutralisation and RNA interference. Transmembrane neuregulin 1 (tNRG1), HER2 and HER3 expression was analysed in primary CRC (n=54), adjacent normal colorectal tissues (n=4), liver metastases (n=3) and adjacent normal liver tissues (n=3) by immunohistochemistry. BM-MSC stimulate invasion, survival and tumorigenesis of CRC through the release of soluble NRG1, activating the HER2/HER3-dependent PI3K/AKT signalling cascade in CRC cells. Similarly, tumour-associated mesenchymal cells (T-MC) in CRC demonstrate high tNRG1 expression, which is significantly associated with advanced Union for International Cancer Control stage (p=0.005) and invasion depth (p=0.04) and decreased 5-year progression-free survival (p=0.01). HER2 and HER3 show membrane localisation in cancer cells of CRC tissue. Paracrine NRG1/HER3 signals initiated by BM-MSC and T-MC promote CRC cell progression, and high tNRG1 expression is associated with poor prognosis in CRC.

  9. Progress in the surgery of rectal cancer

    Directory of Open Access Journals (Sweden)

    Rudolf Schiessel

    2018-01-01

    Full Text Available The treatment of rectal cancer has been improved a great deal within the last 20 years. Major progress has been made in the preoperative evaluation by introducing MRI- imaging as a basis for the further management. Neoadjuvant radiochemotherapy has been shown to be effective in downstaging of advanced tumours. The surgical technique has been improved in many respects.- Total mesorectal excision has reduced local recurrences, sphincter saving techniques such as low anterior resection and intersphincteric resection reduced the need for a permanent stoma to 10%-20%. Recently the introduction of minimal invasive techniques and the application of robotic systems have reduced the surgical trauma.

  10. Discovering biological progression underlying microarray samples.

    Directory of Open Access Journals (Sweden)

    Peng Qiu

    2011-04-01

    Full Text Available In biological systems that undergo processes such as differentiation, a clear concept of progression exists. We present a novel computational approach, called Sample Progression Discovery (SPD, to discover patterns of biological progression underlying microarray gene expression data. SPD assumes that individual samples of a microarray dataset are related by an unknown biological process (i.e., differentiation, development, cell cycle, disease progression, and that each sample represents one unknown point along the progression of that process. SPD aims to organize the samples in a manner that reveals the underlying progression and to simultaneously identify subsets of genes that are responsible for that progression. We demonstrate the performance of SPD on a variety of microarray datasets that were generated by sampling a biological process at different points along its progression, without providing SPD any information of the underlying process. When applied to a cell cycle time series microarray dataset, SPD was not provided any prior knowledge of samples' time order or of which genes are cell-cycle regulated, yet SPD recovered the correct time order and identified many genes that have been associated with the cell cycle. When applied to B-cell differentiation data, SPD recovered the correct order of stages of normal B-cell differentiation and the linkage between preB-ALL tumor cells with their cell origin preB. When applied to mouse embryonic stem cell differentiation data, SPD uncovered a landscape of ESC differentiation into various lineages and genes that represent both generic and lineage specific processes. When applied to a prostate cancer microarray dataset, SPD identified gene modules that reflect a progression consistent with disease stages. SPD may be best viewed as a novel tool for synthesizing biological hypotheses because it provides a likely biological progression underlying a microarray dataset and, perhaps more importantly, the

  11. Invasion genetics of emerald ash borer in North America

    Science.gov (United States)

    Alicia M. Bray; Leah S. Bauer; Robert A. Haack; Therese Poland; James J. Smith

    2006-01-01

    Emerald ash borer (EAB) was first detected in Michigan and Canada in 2002. Efforts to eradicate this destructive pest by federal and state regulatory agencies continue. Knowledge of EAB genetics will be useful in understanding the invasion dynamics of the beetle and to help identify geographic localities of potential biocontrol agents.

  12. Frequency and Therapeutic Outcomes of Culture Positive Invasive ...

    African Journals Online (AJOL)

    From May 2012 to July 2013, all cases from consults sent to the clinical microbiologists for review and patients with positive samples were identified from the mycology laboratory registers. Hospital based frequency of Invasive Fungal Infections was 42.5%. Patients' ages ranged from 5 days to 71 years with a median of 29 ...

  13. Learning from our mistakes: minimizing problems with invasive biofuel plants

    CSIR Research Space (South Africa)

    Richardson, DM

    2011-03-01

    Full Text Available . Economic driving forces are crucial. Important lessons to be learnt from forestry for reducing problems with invasiveness of alien species for biofuel production include: the use of global databases and screening tools for identifying high-risk species...

  14. Invasive hemodynamic characterization of heart failure with preserved ejection fraction

    DEFF Research Database (Denmark)

    Andersen, Mads Jønsson; Borlaug, Barry A

    2014-01-01

    Recent hemodynamic studies have advanced our understanding of heart failure with preserved ejection fraction (HFpEF). Despite improved pathophysiologic insight, clinical trials have failed to identify an effective treatment for HFpEF. Invasive hemodynamic assessment can diagnose or exclude HFp...... of pathophysiological differences and inform the design and entry criteria for future trials....

  15. Notch1 is required for hypoxia-induced proliferation, invasion and chemoresistance of T-cell acute lymphoblastic leukemia cells

    Directory of Open Access Journals (Sweden)

    Zou Jie

    2013-01-01

    Full Text Available Abstract Background Notch1 is a potent regulator known to play an oncogenic role in many malignancies including T-cell acute lymphoblastic leukemia (T-ALL. Tumor hypoxia and increased hypoxia-inducible factor-1α (HIF-1α activity can act as major stimuli for tumor aggressiveness and progression. Although hypoxia-mediated activation of the Notch1 pathway plays an important role in tumor cell survival and invasiveness, the interaction between HIF-1α and Notch1 has not yet been identified in T-ALL. This study was designed to investigate whether hypoxia activates Notch1 signalling through HIF-1α stabilization and to determine the contribution of hypoxia and HIF-1α to proliferation, invasion and chemoresistance in T-ALL. Methods T-ALL cell lines (Jurkat, Sup-T1 transfected with HIF-1α or Notch1 small interference RNA (siRNA were incubated in normoxic or hypoxic conditions. Their potential for proliferation and invasion was measured by WST-8 and transwell assays. Flow cytometry was used to detect apoptosis and assess cell cycle regulation. Expression and regulation of components of the HIF-1α and Notch1 pathways and of genes related to proliferation, invasion and apoptosis were assessed by quantitative real-time PCR or Western blot. Results Hypoxia potentiated Notch1 signalling via stabilization and activation of the transcription factor HIF-1α. Hypoxia/HIF-1α-activated Notch1 signalling altered expression of cell cycle regulatory proteins and accelerated cell proliferation. Hypoxia-induced Notch1 activation increased the expression of matrix metalloproteinase-2 (MMP2 and MMP9, which increased invasiveness. Of greater clinical significance, knockdown of Notch1 prevented the protective effect of hypoxia/HIF-1α against dexamethasone-induced apoptosis. This sensitization correlated with losing the effect of hypoxia/HIF-1α on Bcl-2 and Bcl-xL expression. Conclusions Notch1 signalling is required for hypoxia/HIF-1α-induced proliferation

  16. Co-evolution of cancer microenvironment reveals distinctive patterns of gastric cancer invasion: laboratory evidence and clinical significance

    Directory of Open Access Journals (Sweden)

    Li Yan

    2010-10-01

    MVD group than high MVD group (median OS 39.0 vs 8.5 mo, P = 0.001. The difference of disease-free survival (DFS between low MVD group and high MVD group was not statistically significant (P = 0.260. Four typical patterns of cancer invasion were identified based on histological study of the cancer tissue, including Washing pattern, Ameba-like pattern, Spindle pattern and Linear pattern. Conclusions Proteolytic enzymes MMP9, MMP2 and macrophages in stroma contribute to GC progression by facilitating the angiogenesis. Cancer invasion patterns may help predict GC metastasis.

  17. Drug-induced progressive multifocal leukoencephalopathy

    DEFF Research Database (Denmark)

    Vermeer, N S; Straus, S M J M; Mantel-Teeuwisse, A K

    2015-01-01

    Progressive multifocal leukoencephalopathy (PML) has been identified as a serious adverse drug reaction (ADR) of several immunomodulatory biologicals. In this study, we contrasted the reporting patterns of PML for two biologicals for which the risk was identified at different points in their life......Progressive multifocal leukoencephalopathy (PML) has been identified as a serious adverse drug reaction (ADR) of several immunomodulatory biologicals. In this study, we contrasted the reporting patterns of PML for two biologicals for which the risk was identified at different points...

  18. The E-cadherin repressor slug and progression of human extrahepatic hilar cholangiocarcinoma

    Directory of Open Access Journals (Sweden)

    Wang Xin-sheng

    2010-07-01

    Full Text Available Abstract Objectives This study explored the expression and function of Slug in human extrahepatic hilar cholangiocarcinoma (EHC to identify its role in tumor progression. Methods The expression of Snail and Slug mRNA in 52 human tissue samples of EHC was investigated. The mRNA of Snail and Slug were quantified using reverse transcriptase-PCR, and correlations with E-cadherin expression and clinicopathological factors were investigated. We then investigated transfection of Slug cDNA in endogenous E-cadherin-positive human EHC FRH0201 cells, selectively induced the loss of E-cadherin protein expression, and then small interfering RNA (siRNA for inhibition of Slug expression in endogenous Slug-positive human EHC QBC939 cells, selectively induced the loss of Slug protein expression. A Boyden chamber transwell assay was used for invasion. Results Slug mRNA was overexpressed in 18 cases (34.6% of EHC compared with adjacent noncancerous tissue. E-Cadherin protein expression determined in the same 52 cases by immunohistochemistry was significantly down-regulated in those cases with Slug mRNA overexpression (P = 0.0001. The tumor and nontumor ratio of Slug mRNA was correlated with nodal metastasis(p = 0.0102, distant metastasis (p = 0.0001and Survival time(p = 0.0443. However, Snail mRNA correlated with neither E-cadherin expression nor tumor invasiveness. By inhibiting Slug expression by RNA interference, we found that reduced Slug levels upregulated E-cadherin and decreased invasion in QBC939 cell. When the QBC939 cells was infected with Slug cDNA,, significant E-cadherin was downregulated and increased invasion in QBC939 cell. Conclusions The results suggested that Slug expression plays an important role in both the regulation of E-cadherin expression and in the acquisition of invasive potential in human EHC. Slug is possibly a potential target for an antitumor therapy blocking the functions of invasion and metastasis in human EHCs.

  19. Polo-like Kinase I is involved in Invasion through Extracellular Matrix

    Energy Technology Data Exchange (ETDEWEB)

    Bissell, Mina J; Rizki, Aylin; Mott, Joni D.; Bissell, Mina J

    2008-04-02

    Polo-like kinase 1, PLK1, has important functions in maintaining genome stability and is involved in regulation of mitosis. PLK1 is up regulated in many invasive carcinomas. We asked whether it may also play a role in acquisition of invasiveness, a crucial step in transition to malignancy. In a model of metaplastic basal-like breast carcinoma progression, we found that PLK1 expression is necessary but not sufficient to induce invasiveness through laminin-rich extracellular matrix. PLK1 mediates invasion via Vimentin and {beta}1 integrin, both of which are necessary. We observed that PLK1 phosphorylates Vimentin on serine 82, which in turn regulates cell surface levels of {beta}1 integrin. We found PLK1 to be also highly expressed in pre-invasive in situ carcinomas of the breast. These results support a role for the involvement of PLK1 in the invasion process and point to this pathway as a potential therapeutic target for pre-invasive and invasive breast carcinoma treatment.

  20. MMP28 (epilysin) as a novel promoter of invasion and metastasis in gastric cancer

    International Nuclear Information System (INIS)

    Jian, Pan; Yanfang, Tao; Zhuan, Zhou; Jian, Wang; Xueming, Zhu; Jian, Ni

    2011-01-01

    The purpose of this study was to investigate invasion and metastasis related genes in gastric cancer. The transwell migration assay was used to select a highly invasive sub-line from minimally invasive parent gastric cancer cells, and gene expression was compared using a microarray. MMP28 upregulation was confirmed using qRT-PCR. MMP28 immunohistochemistry was performed in normal and gastric cancer specimens. Invasiveness and tumor formation of stable cells overexpressing MMP28 were tested in vitro and in vivo. MMP28 was overexpressed in the highly invasive sub-cell line. Immunohistochemistry revealed MMP28 expression was markedly increased in gastric carcinoma relative to normal epithelia, and was significantly associated with depth of tumor invasion, lymph node metastasis and poorer overall survival. Ectopic expression of MMP28 indicated MMP28 promoted tumor cell invasion in vitro and increased gastric carcinoma metastasis in vivo. This study indicates MMP28 is frequently overexpressed during progression of gastric carcinoma, and contributes to tumor cell invasion and metastasis. MMP28 may be a novel therapeutic target for prevention and treatment of metastases in gastric cancer

  1. The biogeography of threatened insular iguanas and opportunities for invasive vertebrate management

    Science.gov (United States)

    Tershy, Bernie R.; Newton, Kelly M.; Spatz, Dena R.; Swinnerton, Kirsty; Iverson, John B.; Fisher, Robert N.; Harlow, Peter S.; Holmes, Nick D.; Croll, Donald A.; Iverson, J.B.; Grant, T. D.; Knapp, C. R.; Pasachnik, S. A.

    2016-01-01

    Iguanas are a particularly threatened group of reptiles, with 61% of species at risk of extinction. Primary threats to iguanas include habitat loss, direct and indirect impacts by invasive vertebrates, overexploitation, and human disturbance. As conspicuous, charismatic vertebrates, iguanas also represent excellent flagships for biodiversity conservation. To assist planning for invasive vertebrate management and thus benefit threatened iguana recovery, we identified all islands with known extant or extirpated populations of Critically Endangered and Endangered insular iguana taxa as recognized by the International Union for Conservation of Nature (IUCN) Red List of Threatened Species. For each island, we determined total area, sovereignty, the presence of invasive alien vertebrates, and human population. For the 23 taxa of threatened insular iguanas we identified 230 populations, of which iguanas were extant on 185 islands and extirpated from 45 islands. Twenty-one iguana taxa (91% of all threatened insular iguana taxa) occurred on at least one island with invasive vertebrates present; 16 taxa had 100% of their population(s) on islands with invasive vertebrates present. Rodents, cats, ungulates, and dogs were the most common invasive vertebrates. We discuss biosecurity, eradication, and control of invasive vertebrates to benefit iguana recovery: (1) on islands already free of invasive vertebrates; (2) on islands with high iguana endemicity; and (3) for species and subspecies with small total populations occurring across multiple small islands. Our analyses provide an important first step toward understanding how invasive vertebrate management can be planned effectively to benefit threatened insular iguanas.

  2. Predicting periodontitis progression?

    Science.gov (United States)

    Ferraiolo, Debra M

    2016-03-01

    determining the suitability of data for further quantitative analysis (meta-analysis). Unfortunately, the heterogeneity of the data did not allow. After screening, 19 studies fitted the inclusion criteria of identifying five different patient-based periodontal risk assessment tools. DenPlan Excel/Previsor Patient Assessment (DEP-PA) and its modifications were used in five studies. The HIDEP model, the dentition risk system (DRS) and the risk assessment-based individualised treatment (RABIT) were each used in one study. Lastly, the periodontal risk assessment (PRA) and its modifications were found in 12 publications.PRA uses the following factors to assess risk of recurrence of disease: Percentage of bleeding on probing, loss of teeth from a total of 28 teeth, loss of periodontal support in relation to the patient's age, prevalence of residual pockets greater than 4 mm (3-5 mm), systemic and genetic conditions and environmental factors, such as cigarette smoking.Ten included studies had cohort designs (N= 2130) spanning three to 12 years with different follow-up times. Generally, these studies reflected that different assessment tools were able to separate subjects with differing probability of disease progression and tooth loss. The observed effect was dose dependent (the higher the estimation of risk the higher the level of observed disease or tooth loss).Six cross sectional studies (N=1078) reported the comparison of different assessment tools, adjusted or unadjusted associations with periodontal disease and subjective risk assessments provided by the tools. There were three articles noted in the flow diagram as articles proposing the tool. Qualitative analysis reflects that parameters are similar across the studies but differences are present in how these parameters were assessed. In treated populations, results of patient-based risk assessments predicted periodontitis progression and tooth loss in various populations. Additional research on the utility of risk assessment

  3. Accuracy of percutaneous lung biopsy for invasive pulmonary aspergillosis

    International Nuclear Information System (INIS)

    Hoffer, F.A.; Gow, K.; Davidoff, A.; Flynn, P.M.

    2001-01-01

    Background. Invasive pulmonary aspergillosis is fulminant and often fatal in immunosuppressed patients. Percutaneous biopsy may select patients who could benefit from surgical resection. Objective. We sought to determine the accuracy of percutaneous biopsy for pediatric invasive pulmonary aspergillosis. Materials and methods. We retrospectively reviewed 28 imaging-guided percutaneous biopsies of the lungs of 24 children with suspected pulmonary aspergillosis. Twenty-two were being treated for malignancy and two for congenital immunodeficiency; 15 had received bone-marrow transplants. The accuracy of the percutaneous lung biopsy was determined by subsequent surgical resection, autopsy, or clinical course. Results. Histopathological studies showed ten biopsy specimens with septate hyphae, indicating a mold, and seven with Aspergillus flavus colonies in culture. The remaining 18 biopsies revealed no fungi. No patient had progressive aspergillosis after negative biopsy. Invasive pulmonary mold was detected by percutaneous biopsy with 100 % (10/10) sensitivity and 100 % (18/18) specificity. Percutaneous biopsy results influenced the surgical decision in 86 % (24 of 28) of the cases. Bleeding complicated the biopsy in 46 % (13/28) and hastened one death. Conclusion. Percutaneous biopsy of the lung is an accurate technique for the diagnosis of invasive pulmonary aspergillosis and correctly determines which immunosuppressed pediatric patients would benefit from therapeutic pulmonary resection. (orig.)

  4. Conservative Management of Invasive Cervical Resorption: A Case Report

    Directory of Open Access Journals (Sweden)

    Farhan Raza Khan

    2013-01-01

    Full Text Available Invasive cervical resorption is a condition that affects the root surface area below the epithelial attachment. Multiple treatment modalities are advocated, involving exposure of the invasive defect, removal of the granulation tissue and sealing with various restorative materials. This report demonstrates conservative treatment of a patient presenting with peri-apical periodontitis in upper right central and lateral incisors, along with Class II invasive resorption defect cervically on the mesial aspect of the central incisor, as a result of trauma. As the patient was not willing for any surgical intervention, only ortho-grade root canal treatment was carried out in both teeth, with Calcium hydroxide as intra-canal medicament. At three year follow-up, the patient remains asymptomatic demonstrating radiographic evidence of infilling of defect with bone-like tissue.Within the limitations of this report, it was seen that this conservative method for halting the progression of invasive cervical resorption could be under taken in patients who are un-willing for surgical intervention or in whom surgery is contra-indicated.

  5. Invasive exotic plants suffer less herbivory than non-invasive exotic plants

    OpenAIRE

    Cappuccino, Naomi; Carpenter, David

    2005-01-01

    We surveyed naturally occurring leaf herbivory in nine invasive and nine non-invasive exotic plant species sampled in natural areas in Ontario, New York and Massachusetts, and found that invasive plants experienced, on average, 96% less leaf damage than non-invasive species. Invasive plants were also more taxonomically isolated than non-invasive plants, belonging to families with 75% fewer native North American genera. However, the relationship between taxonomic isolation at the family level ...

  6. Lumbar Spinal Stenosis Associated With Degenerative Lumbar Spondylolisthesis: A Systematic Review and Meta-analysis of Secondary Fusion Rates Following Open vs Minimally Invasive Decompression.

    Science.gov (United States)

    Schöller, Karsten; Alimi, Marjan; Cong, Guang-Ting; Christos, Paul; Härtl, Roger

    2017-03-01

    Decompression without fusion is a treatment option in patients with lumbar spinal stenosis (LSS) associated with stable low-grade degenerative spondylolisthesis (DS). A minimally invasive unilateral laminotomy (MIL) for "over the top" decompression might be a less destabilizing alternative to traditional open laminectomy (OL). To review secondary fusion rates after open vs minimally invasive decompression surgery. We performed a literature search in Pubmed/MEDLINE using the keywords "lumbar spondylolisthesis" and "decompression surgery." All studies that separately reported the outcome of patients with LSS+DS that were treated by OL or MIL (transmuscular or subperiosteal route) were included in our systematic review and meta-analysis. The primary end point was secondary fusion rate. Secondary end points were total reoperation rate, postoperative progression of listhetic slip, and patient satisfaction. We identified 37 studies (19 with OL, 18 with MIL), with a total of 1156 patients, that were published between 1983 and 2015. The studies' evidence was mostly level 3 or 4. Secondary fusion rates were 12.8% after OL and 3.3% after MIL; the total reoperation rates were 16.3% after OL and 5.8% after MIL. In the OL cohort, 72% of the studies reported a slip progression compared to 0% in the MIL cohort, respectively. After OL, satisfactory outcome was 62.7% compared to 76% after MIL. In patients with LSS and DS, minimally invasive decompression is associated with lower reoperation and fusion rates, less slip progression, and greater patient satisfaction than open surgery. Copyright © 2017 by the Congress of Neurological Surgeons

  7. Optimal Treatment for Intermediate- and High-Risk, Nonmuscle-Invasive Bladder Cancer

    Directory of Open Access Journals (Sweden)

    A.P.M. van der Meijden

    2006-01-01

    Full Text Available According to clinical and pathological factors the prognosis of a patient with non-muscle invasive bladder tumors can be assessed. The prognosis is determined by the likelihood of recurrence(30-70% and/or progression to muscle invasive bladder cancer(1-15%.Trans urethral resection of bladder tumors remains the initial therapy but adjuvant intravesical instillations are necessary.All patients benefit from a single immediate post operative instillation with a chemotherapeutic agent and for low risk tumors this is the optimal therapy.Patients with intermediate and high risk tumors need more intravesical chemo-or immunotherapy. Chemotherapy reduces recurrences but not progression. Intravesical immunotherapy(BCG prevents or delays progression. Patients at high risk for progression may need upfront cystectomy.

  8. Fibroblast activation protein-α-expressing fibroblasts promote the progression of pancreatic ductal adenocarcinoma.

    Science.gov (United States)

    Kawase, Tomoya; Yasui, Yumiko; Nishina, Sohji; Hara, Yuichi; Yanatori, Izumi; Tomiyama, Yasuyuki; Nakashima, Yoshihiro; Yoshida, Koji; Kishi, Fumio; Nakamura, Masafumi; Hino, Keisuke

    2015-09-02

    Pancreatic ductal adenocarcinoma (PDAC) is characterized by an extensive desmoplastic stromal response. Fibroblast activation protein-α (FAP) is best known for its presence in stromal cancer-associated fibroblasts (CAFs). Our aim was to assess whether FAP expression was associated with the prognosis of patients with PDAC and to investigate how FAP expressing CAFs contribute to the progression of PDAC. FAP expression was immunohistochemically assessed in 48 PDAC specimens. We also generated a fibroblastic cell line stably expressing FAP, and examined the effect of FAP-expressing fibroblasts on invasiveness and the cell cycle in MiaPaCa-2 cells (a pancreatic cancer cell line). Stromal FAP expression was detected in 98% (47/48) of the specimens of PDAC, with the intensity being weak in 16, moderate in 19, and strong in 12 specimens, but was not detected in the 3 control noncancerous pancreatic specimens. Patients with moderate or strong FAP expression had significantly lower cumulative survival rates than those with negative or weak FAP expression (mean survival time; 352 vs. 497 days, P = 0.006). Multivariate analysis identified moderate to strong expression of FAP as one of the factors associated with the prognosis in patients with PDAC. The intensity of stromal FAP expression was also positively correlated to the histological differentiation of PDAC (P fibroblasts promoted the invasiveness of MiaPaCa-2 cells more intensively than fibroblasts not expressing FAP. Coculture with FAP-expressing fibroblasts significantly activated cell cycle shift in MiaPaCa-2 cells compared to coculture with fibroblasts not expressing FAP. Furthermore, coculture with FAP expressing fibroblasts inactivated retinoblastoma (Rb) protein, an inhibitor of cell cycle progression, in MiaPaCa-2 cells by promoting phosphorylation of Rb. The present in vitro results and the association of FAP expression with clinical outcomes provide us with a better understanding of the effect of FAP

  9. The Epidemiology and Diagnosis of Invasive Candidiasis Among Premature Infants

    Science.gov (United States)

    Kelly, Matthew S.; Benjamin, Daniel K.; Smith, P. Brian

    2015-01-01

    Invasive candidiasis is a leading infectious cause of morbidity and mortality in premature infants. Improved recognition of modifiable risk factors and antifungal prophylaxis have contributed to the recent decline in the incidence of this infection among infants. Invasive candidiasis typically occurs in the first six weeks of life and presents with non-specific signs of sepsis. Definitive diagnosis relies on growth of Candida in blood culture or cultures from other normally sterile sites, but this may identify fewer than half of cases. Improved diagnostics are needed to guide initiation of antifungal therapy in premature infants. PMID:25677999

  10. Mini-invasive nonsurgical treatment of class 4 invasive cervical resorption: a case series

    Directory of Open Access Journals (Sweden)

    Stefano Salzano

    2016-06-01

    Full Text Available Invasive Cervical Resorption (ICR is a pathological process that can lead to a progressive tooth destruction over time, as dentin is gradually replaced by granulomatous tissue. Unfortunately ICR is difficult to diagnose because it is often asymptomatic and can easily be mistaken for a carious lesion, especially in the early stages. According to the existing literature, class IV ICR treatment shows a success rate of 12.5% when the lesion affects more than one third of the root. In this paper we describe the conservative, nonsurgical approach we adopted in treating 5 cases of class IV ICR with the help of cone-beam computed tomography and operating microscope. Resorptions were filled with MTA in three cases and with Biodentine in two cases. The follow-up period ranged from 3 months to 2 years. All patients were found to be asymptomatic and check-up radiographic examinations did not show any signs of ICR relapse.

  11. MEIS1 inhibits clear cell renal cell carcinoma cells proliferation and in vitro invasion or migration.

    Science.gov (United States)

    Zhu, Jie; Cui, Liang; Xu, Axiang; Yin, Xiaotao; Li, Fanglong; Gao, Jiangping

    2017-03-07

    Myeloid ecotropic viral integration site 1 (MEIS1) protein plays a synergistic causative role in acute myeloid leukemia (AML). However, MEIS1 has also shown to be a potential tumor suppressor in some other cancers, such as non-small-cell lung cancer (NSCLC) and prostate cancer. Although multiple roles of MEIS1 in cancer development and progression have been identified, there is an urgent demand to discover more functions of this molecule for further therapeutic design. MEIS1 was overexpressed via adenovirus vector in clear cell renal cell carcinoma (ccRCC) cells. Western blot and real-time qPCR (quantitative Polymerase Chain Reaction) was performed to examine the protein and mRNA levels of MEIS1. Cell proliferation, survival, in vitro migration and invasion were tested by MTT, colony formation, soft-agar, transwell (in vitro invasion/migration) assays, and tumor in vivo growthwas measured on nude mice model. In addition, flow-cytometry analysis was used to detect cell cycle arrest or non-apoptotic cell death of ccRCC cells induced by MEIS1. MEIS1 exhibits a decreased expression in ccRCC cell lines than that in non-tumor cell lines. MEIS1 overexpression inhibits ccRCC cells proliferation and induces G1/S arrest concomitant with marked reduction of G1/S transition regulators, Cyclin D1 and Cyclin A. Moreover, MEIS1-1 overexpression also induces non-apoptotic cell death of ccRCC cells via decreasing the levels of pro-survival regulators Survivin and BCL-2. Transwell migration assay (TMA) shows that MEIS1 attenuates in vitro invasion and migration of ccRCC cells with down-regulated epithelial-mesenchymal transition (EMT) process. Further, in nude mice model, MEIS1 inhibits the in vivo growth of Caki-1 cells. By investigating the role of MEIS1 in ccRCC cells' survival, proliferation, anchorage-independent growth, cell cycle progress, apoptosis and metastasis, in the present work, we propose that MEIS1 may play an important role in clear cell renal cell carcinoma (cc

  12. The potential of non-invasive ventilation to decrease BPD.

    Science.gov (United States)

    Bhandari, Vineet

    2013-04-01

    Bronchopulmonary dysplasia (BPD), the most common chronic lung disease in infancy, has serious long-term pulmonary and neurodevelopmental consequences right up to adulthood, and is associated with significant healthcare costs. BPD is a multifactorial disease, with genetic and environmental factors interacting to culminate in the characteristic clinical and pathological phenotype. Among the environmental factors, invasive endotracheal tube ventilation is considered a critical contributing factor to the pathogenesis of BPD. Since BPD currently has no specific preventive or effective therapy, considerable interest has focused on the use of non-invasive ventilation as a means to potentially decrease the incidence of BPD. This article reviews the progress made in the last 5 years in the use of nasal continuous positive airways pressure (NCPAP) and nasal intermittent positive pressure ventilation (NIPPV) as it pertains to impacting on BPD rates. Research efforts are summarized, and some guidelines are suggested for clinical use of these techniques in neonates. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Non-invasive mechanical ventilation

    African Journals Online (AJOL)

    Nicky

    failure may benefit from a trial of NIV. Increased work of breathing, as noted by use of accessory breathing. SAJCC. 10. July 2005, V ol. 21, No. 1. University of Manitoba and Manitoba Institute of Child Health, Winnipeg, Canada. B Louise Giles, MD, FRCPC. Non-invasive ventilation (NIV) is a modality of providing airway and ...

  14. Vaccines against invasive Salmonella disease

    Science.gov (United States)

    MacLennan, Calman A; Martin, Laura B; Micoli, Francesca

    2014-01-01

    Though primarily enteric pathogens, Salmonellae are responsible for a considerable yet under-appreciated global burden of invasive disease. In South and South-East Asia, this manifests as enteric fever caused by serovars Typhi and Paratyphi A. In sub-Saharan Africa, a similar disease burden results from invasive nontyphoidal Salmonellae, principally serovars Typhimurium and Enteritidis. The existing Ty21a live-attenuated and Vi capsular polysaccharide vaccines target S. Typhi and are not effective in young children where the burden of invasive Salmonella disease is highest. After years of lack of investment in new Salmonella vaccines, recent times have seen increased interest in the area led by emerging-market manufacturers, global health vaccine institutes and academic partners. New glycoconjugate vaccines against S. Typhi are becoming available with similar vaccines against other invasive serovars in development. With other new vaccines under investigation, including live-attenuated, protein-based and GMMA vaccines, now is an exciting time for the Salmonella vaccine field. PMID:24804797

  15. Invasive cranial mycosis our experiences

    Directory of Open Access Journals (Sweden)

    Tapas Kumbhkar

    2013-01-01

    Full Text Available Fungi can cause serious cranial infections in immunocompromised and diabetic patients. Common pathogens mainly include Aspergillus and Mucor. These organisms cause tissue invasion and destruction of adjacent structures (e.g. orbit, ethmoid, sphenoid, maxillary & cavernous sinuses. Mortality and morbidity rate is high despite combined surgical, antifungal and antidiabetic treatment. We present our experience of six cases with such infection.

  16. Biological invasions in forest ecosystems

    Science.gov (United States)

    Andrew M. Liebhold; Eckehard G. Brockerhoff; Susan Kalisz; Martin A. Nuñez; David A. Wardle; Michael J. Wingfield

    2017-01-01

    Forests play critical roles in global ecosystem processes and provide numerous services to society. But forests are increasingly affected by a variety of human influences, especially those resulting from biological invasions. Species invading forests include woody and herbaceous plants, many animal species including mammals and invertebrates, as well as a variety of...

  17. Profiling Invasiveness in Head and Neck Cancer: Recent Contributions of Genomic and Transcriptomic Approaches

    Energy Technology Data Exchange (ETDEWEB)

    Nisa, Lluís, E-mail: lluis.nisa@dkf.unibe.ch [Department of Radiation Oncology, Inselspital, Bern University Hospital, and University of Bern, Bern 3010 (Switzerland); Department of Clinical Research, Inselspital, Bern University Hospital, and University of Bern, MEM-E807, Murtenstrasse 35, Bern 3010 (Switzerland); Department of Otorhinolaryngology-Head and Neck Surgery, Inselspital, Bern University Hospital, and University of Bern, Bern 3010 (Switzerland); Aebersold, Daniel Matthias [Department of Radiation Oncology, Inselspital, Bern University Hospital, and University of Bern, Bern 3010 (Switzerland); Department of Clinical Research, Inselspital, Bern University Hospital, and University of Bern, MEM-E807, Murtenstrasse 35, Bern 3010 (Switzerland); Giger, Roland; Caversaccio, Marco Domenico; Borner, Urs [Department of Otorhinolaryngology-Head and Neck Surgery, Inselspital, Bern University Hospital, and University of Bern, Bern 3010 (Switzerland); Medová, Michaela; Zimmer, Yitzhak, E-mail: lluis.nisa@dkf.unibe.ch [Department of Radiation Oncology, Inselspital, Bern University Hospital, and University of Bern, Bern 3010 (Switzerland); Department of Clinical Research, Inselspital, Bern University Hospital, and University of Bern, MEM-E807, Murtenstrasse 35, Bern 3010 (Switzerland)

    2015-03-31

    High-throughput molecular profiling approaches have emerged as precious research tools in the field of head and neck translational oncology. Such approaches have identified and/or confirmed the role of several genes or pathways in the acquisition/maintenance of an invasive phenotype and the execution of cellular programs related to cell invasion. Recently published new-generation sequencing studies in head and neck squamous cell carcinoma (HNSCC) have unveiled prominent roles in carcinogenesis and cell invasion of mutations involving NOTCH1 and PI3K-patwhay components. Gene-expression profiling studies combined with systems biology approaches have allowed identifying and gaining further mechanistic understanding into pathways commonly enriched in invasive HNSCC. These pathways include antigen-presenting and leucocyte adhesion molecules, as well as genes involved in cell-extracellular matrix interactions. Here we review the major insights into invasiveness in head and neck cancer provided by high-throughput molecular profiling approaches.

  18. Evidence of climatic niche shift during biological invasion

    DEFF Research Database (Denmark)

    Broennimann, O.; Treier, Urs; Müller-Schärer, H.

    2007-01-01

    Niche-based models calibrated in the native range by relating species observations to climatic variables are commonly used to predict the potential spatial extent of species' invasion. This climate matching approach relies on the assumption that invasive species conserve their climatic niche...... in the invaded ranges. We test this assumption by analysing the climatic niche spaces of Spotted Knapweed in western North America and Europe. We show with robust cross-continental data that a shift of the observed climatic niche occurred between native and non-native ranges, providing the first empirical...... evidence that an invasive species can occupy climatically distinct niche spaces following its introduction into a new area. The models fail to predict the current invaded distribution, but correctly predict areas of introduction. Climate matching is thus a useful approach to identify areas at risk...

  19. Tumour heterogeneity promotes collective invasion and cancer metastatic dissemination.

    Science.gov (United States)

    Hallou, Adrien; Jennings, Joel; Kabla, Alexandre J

    2017-08-01

    Heterogeneity within tumour cell populations is commonly observed in most cancers. However, its impact on metastatic dissemination, one of the primary determinants of the disease prognosis, remains poorly understood. Working with a simplified numerical model of tumour spheroids, we investigated the impact of mechanical heterogeneity on the onset of tumour invasion into surrounding tissues. Our work establishes a positive link between tumour heterogeneity and metastatic dissemination, and recapitulates a number of invasion patterns identified in vivo , such as multicellular finger-like protrusions. Two complementary mechanisms are at play in heterogeneous tumours. A small proportion of stronger cells are able to initiate and lead the escape of cells, while collective effects in the bulk of the tumour provide the coordination required to sustain the invasive process through multicellular streaming. This suggests that the multicellular dynamics observed during metastasis is a generic feature of mechanically heterogeneous cell populations and might rely on a limited and generic set of attributes.

  20. CD207+/langerin positive dendritic cells in invasive and in situ cutaneous malignant melanoma

    Directory of Open Access Journals (Sweden)

    Grzegorz Dyduch

    2017-05-01

    Full Text Available Introduction : Dendritic cells are crucial for cutaneous immune response. Their role in melanoma progression is however a matter of controversy. Material and methods : The number of dendritic cells within epidermis and in peri- and intratumoral location was analyzed using CD207 immunostain in 17 cases of in situ and 25 case of invasive melanoma. Results : Average peritumoral CD207+ cells count was 22.88 for all cases, 17.94 for in situ lesions and 26.24 for invasive cases. Average epidermal CD207+ cells count was 164.47 for all cases, 183.00 for in situ lesions and 150.78 – for invasive cases. In case of invasive melanomas, peritumoral CD207+ cells count was positively correlated with Breslow stage (R = 0.59 mitotic activity within the tumor (R = 0.62. Invasive cases with regression showed higher intratumoral and epidermal CD207+ cells count than the ones without (275.00 vs. 95.32 and 173.20 vs. 148.35 but lower peritumoral CD207+ cells count (17.60 vs. 27.26. Invasive cases with ulceration showed higher intratumoral and peritumoral CD207+ cells count than the ones without ulceration (220.08 vs. 55.67 and 44.17 vs. 9.69. Conclusions : CD207+ cells play a role in both progression and regression of melanoma but their exact role needs further studies.

  1. Motor Speech Phenotypes of Frontotemporal Dementia, Primary Progressive Aphasia, and Progressive Apraxia of Speech

    Science.gov (United States)

    Poole, Matthew L.; Brodtmann, Amy; Darby, David; Vogel, Adam P.

    2017-01-01

    Purpose: Our purpose was to create a comprehensive review of speech impairment in frontotemporal dementia (FTD), primary progressive aphasia (PPA), and progressive apraxia of speech in order to identify the most effective measures for diagnosis and monitoring, and to elucidate associations between speech and neuroimaging. Method: Speech and…

  2. RSK1 activation promotes invasion in nodular melanoma.

    Science.gov (United States)

    Salhi, Amel; Farhadian, Joshua A; Giles, Keith M; Vega-Saenz de Miera, Eleazar; Silva, Ines P; Bourque, Caitlin; Yeh, Karen; Chhangawala, Sagar; Wang, Jinhua; Ye, Fei; Zhang, David Y; Hernando-Monge, Eva; Houvras, Yariv; Osman, Iman

    2015-03-01

    The two major melanoma histologic subtypes, superficial spreading and nodular melanomas, differ in their speed of dermal invasion but converge biologically once they invade and metastasize. Herein, we tested the hypothesis that distinct molecular alterations arising in primary melanoma cells might persist as these tumors progress to invasion and metastasis. Ribosomal protein S6 kinase, 90 kDa, polypeptide 1 (RSK1; official name RPS6KA1) was significantly hyperactivated in human melanoma lines and metastatic tissues derived from nodular compared with superficial spreading melanoma. RSK1 was constitutively phosphorylated at Ser-380 in nodular but not superficial spreading melanoma and did not directly correlate with BRAF or MEK activation. Nodular melanoma cells were more sensitive to RSK1 inhibition using siRNA and the pharmacological inhibitor BI-D1870 compared with superficial spreading cells. Gene expression microarray analyses revealed that RSK1 orchestrated a program of gene expression that promoted cell motility and invasion. Differential overexpression of the prometastatic matrix metalloproteinase 8 and tissue inhibitor of metalloproteinases 1 in metastatic nodular compared with metastatic superficial spreading melanoma was observed. Finally, using an in vivo zebrafish model, constitutive RSK1 activation increased melanoma invasion. Together, these data reveal a novel role for activated RSK1 in the progression of nodular melanoma and suggest that melanoma originating from different histologic subtypes may be biologically distinct and that these differences are maintained as the tumors invade and metastasize. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  3. Introducing the Global Register of Introduced and Invasive Species

    Science.gov (United States)

    Pagad, Shyama; Genovesi, Piero; Carnevali, Lucilla; Schigel, Dmitry; McGeoch, Melodie A.

    2018-01-01

    Harmonised, representative data on the state of biological invasions remain inadequate at country and global scales, particularly for taxa that affect biodiversity and ecosystems. Information is not readily available in a form suitable for policy and reporting. The Global Register of Introduced and Invasive Species (GRIIS) provides the first country-wise checklists of introduced (naturalised) and invasive species. GRIIS was conceived to provide a sustainable platform for information delivery to support national governments. We outline the rationale and methods underpinning GRIIS, to facilitate transparent, repeatable analysis and reporting. Twenty country checklists are presented as exemplars; GRIIS Checklists for close to all countries globally will be submitted through the same process shortly. Over 11000 species records are currently in the 20 country exemplars alone, with environmental impact evidence for just over 20% of these. GRIIS provides significant support for countries to identify and prioritise invasive alien species, and establishes national and global baselines. In future this will enable a global system for sustainable monitoring of trends in biological invasions that affect the environment. PMID:29360103

  4. Implementing invasive species management in an adaptive management framework

    Directory of Open Access Journals (Sweden)

    Llewellyn C. Foxcroft

    2011-05-01

    Full Text Available Adaptive management theory has attracted substantial interest in recent years, in natural resource management in general and also for invasive alien species management. However, whilst many theoretical and conceptual advances have been made, documented cases of practical applications are rare. Coupling invasive species management components with adaptive feedback processes is not without challenges, requiring a substantial change in the thinking and practice of all those involved. Drawing on a decade of experience in South African National Parks, we suggest an approach to implementing adaptive management for controlling invasive alien species. Whilst efforts have been made to advance components of the overall management strategy, the absence of a framework for decision making and feedback mechanisms, inflexibility in the system and shortcomings in the governance structure are all identified as barriers to learning and knowledge integration for the purposes of effective invasive alien species management. The framework provided here, encompassing documents, committees and processes, is aimed at addressing these shortcomings.Conservation implication: Adaptive management theory offers a robust tool for managing inherently complex systems. Its practical application, however, requires distilling the theory into useable functions. We offer a framework to advance implementation of strategic adaptive management for the control of invasive alien species using experiences gained from South African National Parks.

  5. Invasive fungal infections in renal transplant recipients: about 11 cases.

    Science.gov (United States)

    Trabelsi, H; Néji, S; Sellami, H; Yaich, S; Cheikhrouhou, F; Guidara, R; Charffedine, K; Makni, F; Hachicha, J; Ayadi, A

    2013-12-01

    Invasive fungal infections are a major complication and an important cause of morbidity and mortality among solid organ transplant recipients. Their diagnosis is difficult and their prognosis is often pejorative. The aim of this study was to report the cases of invasive fungal infections in renal transplant recipients in Habib Bourguiba Sfax university hospital and to identify the main fungal agents. It is a retrospective study of invasive fungal infections in renal transplant recipient reported in our hospital from January 1995 to February 2013. Invasive fungal infections were diagnosed in 11 cases (3.4%) among 321 renal transplant recipients. These infections included four cases of pneumocystosis, two cases of candidiasis, two cases of aspergillosis, two cases of cryptococcosis and one case of mucormycosis. There were six men and five women. The mean age was 37 years. The infection was late in 63% of cases (>3 months after transplantation). The prolonged corticosteroid and immunosuppressive therapy were the main risk factors (100%) followed by renal failure (45%), graft rejection (45%), broad spectrum antibiotics (45%), CMV infection (36%), neutropenia (36%) and dialysis (18%). The evolution under treatment was favourable only in two cases (18%). Invasive fungal infections are not common among kidney transplant recipients. However, they remain an important cause of morbidity and mortality in this group of patients. Prevention, early diagnosis and appropriate management are necessary to improve prognosis and reduce mortality rate. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  6. The long noncoding RNA HOTAIR promotes colorectal cancer progression by sponging miR-197.

    Science.gov (United States)

    Lu, Xinyang; Liu, Zhiqiang; Ning, Xiaofei; Huang, Lunhua; Jiang, Biao

    2017-11-14

    The long non-coding RNA HOX transcript antisense RNA (HOTAIR) has been found overexpressed in many human malignancies and involved in tumor progression and metastasis. Although the downstream target through which HOTAIR modulates tumor metastasis is not well-known, evidence suggests that microRNA-197 (miR-197) might be involved in this event. In the present study, the significance of HOTAIR and miR-197 in the progression of colorectal cancer were detected in vitro and in vivo. We found that HOTAIR expression was significantly increased in colorectal cancer cells and tissues. In contrast, the expression of miR-197 was obviously decreased. We further demonstrated that HOTAIR knockdown promoted apoptosis and inhibited cell proliferation, migration and invasion in vitro and in vivo. Moreover, HOTAIR modulated the progression of colorectal cancer by competitively binding miR-197. Taken together, our study has identified a novel pathway through which HOTAIR exerts its oncogenic role, and provided a molecular basis for potential applications of HOTAIR in the prognosis and treatment of colorectal cancer.

  7. Effects of Lantana camara (L.) invasion on the native vegetation of ...

    African Journals Online (AJOL)

    . Lantana ... A total of 41 native woody species and 2 native herbaceous species were identified in the study area. Basal area ... in the area. Keywords : Alien plants, Biodiversity, Invasive plants, Lantana camara, Vegetation composition.

  8. Quantitative genome-wide methylation analysis of high-grade non-muscle invasive bladder cancer.

    Science.gov (United States)

    Kitchen, Mark O; Bryan, Richard T; Emes, Richard D; Glossop, John R; Luscombe, Christopher; Cheng, K K; Zeegers, Maurice P; James, Nicholas D; Devall, Adam J; Mein, Charles A; Gommersall, Lyndon; Fryer, Anthony A; Farrell, William E

    2016-03-03

    High-grade non-muscle invasive bladder cancer (HG-NMIBC) is a clinically unpredictable disease with greater risks of recurrence and progression relative to their low-intermediate-grade counterparts. The molecular events, including those affecting the epigenome, that characterize this disease entity in the context of tumor development, recurrence, and progression, are incompletely understood. We therefore interrogated genome-wide DNA methylation using HumanMethylation450 BeadChip arrays in 21 primary HG-NMIBC tumors relative to normal bladder controls. Using strict inclusion-exclusion criteria we identified 1,057 hypermethylated CpGs within gene promoter-associated CpG islands, representing 256 genes. We validated the array data by bisulphite pyrosequencing and examined 25 array-identified candidate genes in an independent cohort of 30 HG-NMIBC and 18 low-intermediate-grade NMIBC. These analyses revealed significantly higher methylation frequencies in high-grade tumors relative to low-intermediate-grade tumors for the ATP5G2, IRX1 and VAX2 genes (P<0.05), and similarly significant increases in mean levels of methylation in high-grade tumors for the ATP5G2, VAX2, INSRR, PRDM14, VSX1, TFAP2b, PRRX1, and HIST1H4F genes (P<0.05). Although inappropriate promoter methylation was not invariantly associated with reduced transcript expression, a significant association was apparent for the ARHGEF4, PON3, STAT5a, and VAX2 gene transcripts (P<0.05). Herein, we present the first genome-wide DNA methylation analysis in a unique HG-NMIBC cohort, showing extensive and discrete methylation changes relative to normal bladder and low-intermediate-grade tumors. The genes we identified hold significant potential as targets for novel therapeutic intervention either alone, or in combination, with more conventional therapeutic options in the treatment of this clinically unpredictable disease.

  9. Approaching invasive species in Madagascar | Kull | Madagascar ...

    African Journals Online (AJOL)

    invasive', the topic of invasive species has until recently received less attention here than in other island contexts. Some species, often alien to Madagascar and introduced by humans, have expanded their range rapidly and have had both ...

  10. Invasive thymoma: CT diagnosis and evaluation

    International Nuclear Information System (INIS)

    Sun Zhonghua; Yu Hong; Liu Hengshun; Yan Hongzhen; Zhang Shurong

    1998-01-01

    Purpose: To study the CT manifestation of invasive thymoma for staging and treatment planning. Materials and methods: The authors reviewed and analyzed the CT scans of 26 patients with invasive thymoma confirmed by surgery and pathology with emphasis on lesion density, invasion of adjacent mediastinal structures, pleural seeding mediastinal nodes and extra-mediastinal metastases. Results: In 26 cases of invasive thymoma, all CT scans demonstrated the soft tissue mass in anterior mediastinum, with heterogeneous density in 16 patients. Irregular invasion to adjacent organs was found in 24 patients. The main findings were mediastinal pleura invasion in 7, lung invasion 9, pleural implants 3, cardiovascular involvement in 20, and cardiophrenic and abdominal invasion in 3. CT is especially effective in detecting the involvement of pleura, pericardium and lung. Conclusion: Computed tomography provides the most reliable assessment of the extent of the disease. Conventional CT scan allows accurate staging and treatment planning

  11. Progressive osseous heteroplasia

    African Journals Online (AJOL)

    Progressive osseous heteroplasia is a rare genetic disorder characterized by cu- taneous ossification during infancy and progressive ossification of subcutane- ous and deep connective tissue including muscle and fascia during childhood. It is at the severe end of a spectrum of Guanine Nucleotide-binding protein,.

  12. CT coronary angiography vs. invasive coronary angiography in CHD

    Directory of Open Access Journals (Sweden)

    Anja Hagen

    2012-04-01

    identified. The first addressed ethical aspects regarding the principles of beneficence, autonomy and justice, and the second addressed those regarding radiation exposition, especially when used within studies.Discussion: The discriminatory power of CT coronary angiography to identify patients with obstructive (above 50 % coronary stenoses should be regarded as “high diagnostic evidence”, to identify patients without coronary stenoses as “persuasive diagnostic evidence”. The discriminatory power of both types of coronary angiography to identify patients with or without functionally relevant coronary stenoses should be regarded as “weak diagnostic evidence”. It can be assumed that patients with a high pretest probability of CHD will need invasive coronary angiography and patients with a low pretest probability of CHD will not need subsequent revascularisation. Therefore, CT coronary angiography may be used before performing invasive coronary angiography in patients with an intermediate pretest probability of CHD. For identifying or excluding of obstructive coronary stenosis, CT coronary angiography was shown to be more cost-saving at a pretest probability of CHD of 50 % or lower, and invasive coronary angiography at a pretest probability of CHD of 70 % or higher. The use of both types of coronary angiography to identify or to exclude functionally relevant coronary stenoses should be regarded as highly cost-consuming. With regard to ethical, social or legal aspects, the following possible implications were identified: under-provision or over-provision of health care, unnecessary complications, anxiety, social stigmatisation, restriction of self-determination, unequal access to health care, unfair resource distribution and legal disputes.Conclusion: From a medical point of view, CT coronary angiography using scanners with at least 64 slices should be recommended as a test to rule out obstructive coronary stenoses in order to avoid inappropriate invasive coronary

  13. Patho-radiologic correlation of invasive pulmonary aspergillosis in the compromised host.

    Science.gov (United States)

    Orr, D P; Myerowitz, R L; Dubois, P J

    1978-05-01

    The autopsy findings and antemortem radiographic abnormalities were correlated in 20 patients with invasive pulmonary aspergillosis to define typical radiographic patterns, their progression and anatomic basis. Sixteen (80%) patients had radiographic abnormalities due to aspergillosis. Fifty-nine percent of the specific radiographic abnormalities seen in these patients were caused by anatomic lesions of asperigillosis and 67% of such anatomic lesions were radiographically definable. The most common initial radiographic pattern was a patchy density (single or multifocal) or a well defined nodule. The densities remained stable in half the patients but progressed, over several weeks to either diffuse consolidation or cavitation in the others. Most anatomic lesions were categorized as either nodular ("target") lesions (1-3 cm in diameter) or hemorrhagic infarctions (5-10 cm in diameter), both due to vascular invasion causing thrombosis and ischemic necrosis. Unlike pulmonary candidiasis, which is usually radiographically undetectable, invasive pulmonary asperigillosis frequently caused radiographically visible lesions.

  14. Minimally Invasive Procedures - Direct and Video-Assisted Forms in the Treatment of Heart Diseases

    Energy Technology Data Exchange (ETDEWEB)

    Castro, Josué Viana Neto, E-mail: jvcn@uol.com.br [Instituto do Coração do Nordeste (INCONE), Fortaleza, CE (Brazil); Universidade de Fortaleza (UNIFOR), Fortaleza, CE (Brazil); Melo, Emanuel Carvalho; Silva, Juliana Fernandes [Instituto do Coração do Nordeste (INCONE), Fortaleza, CE (Brazil); Rebouças, Leonardo Lemos; Corrêa, Larissa Chagas; Germano, Amanda de Queiroz [Universidade de Fortaleza (UNIFOR), Fortaleza, CE (Brazil); Machado, João José Aquino [Instituto do Coração do Nordeste (INCONE), Fortaleza, CE (Brazil)

    2014-03-15

    Minimally invasive cardiovascular procedures have been progressively used in heart surgery. To describe the techniques and immediate results of minimally invasive procedures in 5 years. Prospective and descriptive study in which 102 patients were submitted to minimally invasive procedures in direct and video-assisted forms. Clinical and surgical variables were evaluated as well as the in hospital follow-up of the patients. Fourteen patients were operated through the direct form and 88 through the video-assisted form. Between minimally invasive procedures in direct form, 13 had aortic valve disease. Between minimally invasive procedures in video-assisted forms, 43 had mitral valve disease, 41 atrial septal defect and four tumors. In relation to mitral valve disease, we replaced 26 and reconstructed 17 valves. Aortic clamp, extracorporeal and procedure times were, respectively, 91,6 ± 21,8, 112,7 ± 27,9 e 247,1 ± 20,3 minutes in minimally invasive procedures in direct form. Between minimally invasive procedures in video-assisted forms, 71,6 ± 29, 99,7 ± 32,6 e 226,1 ± 42,7 minutes. Considering intensive care and hospitalization times, these were 41,1 ± 14,7 hours and 4,6 ± 2 days in minimally invasive procedures in direct and 36,8 ± 16,3 hours and 4,3 ± 1,9 days in minimally invasive procedures in video-assisted forms procedures. Minimally invasive procedures were used in two forms - direct and video-assisted - with safety in the surgical treatment of video-assisted, atrial septal defect and tumors of the heart. These procedures seem to result in longer surgical variables. However, hospital recuperation was faster, independent of the access or pathology.

  15. Treatment Options Available for Bacillus Calmette-Guerin Failure in Non-muscle-invasive Bladder Cancer

    NARCIS (Netherlands)

    Yates, D.R.; Brausi, M.A.; Catto, J.W.; Dalbagni, G.; Roupret, M.; Shariat, S.F.; Sylvester, R.J.; Witjes, J.A.; Zlotta, A.R.; Palou-Redorta, J.

    2012-01-01

    CONTEXT: Intravesical bacillus Calmette-Guerin (BCG) is a standard conservative treatment for patients with high-risk non-muscle-invasive bladder cancer (NMIBC). Many patients will experience recurrence or progression following BCG and are termed BCG failures. OBJECTIVE: To summarise the current

  16. Non-invasive imaging of atherosclerosis regression with magnetic resonance to guide drug development

    NARCIS (Netherlands)

    Raggi, Paolo; Baldassarre, Damiano; Day, Simon; de Groot, Eric; Fayad, Z. A.

    2016-01-01

    Slowing of progression and inducing the regression of atherosclerosis with medical therapy have been shown to be associated with an extensive reduction in risk of cardiovascular events. This proof of concept was obtained with invasive angiographic studies but these are, for obvious reasons,

  17. Effects of nutrients on interaction between the invasive bidens pilosa the parasitic cusuta australis

    International Nuclear Information System (INIS)

    Yang, B.; Li, J.; Yan, M.

    2015-01-01

    Parasitic plants have been identified as potential biological agents to control invasive plants. Understanding the interaction between invasive plants and their novel natural enemies is important for understanding mechanisms underlying plant invasion success and thus taking measures to control invasion. We conducted a factorial experiment to test the interactive effects of nutrient addition (low vs. high) and parasitism (with vs. without Cuscuta australis) on the growth of the invasive Bidens pilosa. Parasitism significantly decreased leaf, stem and root biomass of the host invasive plant, and nutrient addition increased leaf and stem biomass of the host. A synergistic effect of parasitism and nutrient addition was found on stem and leaf biomass of the hosts. Nutrient addition significantly increased vegetative biomass of the parasitic plant and caused a more deleterious effect on the invasive host. Reproductive biomass of the parasitic plant was significantly positively related with net photosynthetic rate, light-utilisation efficiency and apparent carboxylation efficiency. Vegetative biomass and total biomass of the parasitic plants were significantly positively related with specific leaf area and the relative chlorophyll content of the host plant. The deleterious effect of the parasite on the growth of the host plant was significantly positively correlated with vegetative biomass of the parasitic plant. Nutrient addition increased the negative effect of the parasitic plant on the invasive host, indicating that the parasitic plant is potentially a biological control agent for the invasive plant even in the context of changing global resources. (author)

  18. Invasion of Nostocales (cyanobacteria) to Subtropical and Temperate Freshwater Lakes - Physiological, Regional, and Global Driving Forces.

    Science.gov (United States)

    Sukenik, Assaf; Hadas, Ora; Kaplan, Aaron; Quesada, Antonio

    2012-01-01

    Similar to the increased number of studies on invasive plants and animals in terrestrial and aquatic ecosystems, many reports were recently published on the invasion of Nostocales (cyanobacteria) to freshwater environments worldwide. Invasion and proliferation of Nostocales in new habitats have the potential to significantly alter the structure of the native community and to modify ecosystem functioning. But most importantly, they influence the water quality due to a variety of toxic compounds that some species produce. Therefore a special attention was given to the invasion and persistence of toxic cyanobacteria in many aquatic ecosystems. Here we summarize the currently published records on the invasion of two Nostocales genera, Cylindrospermopsis and Aphanizomenon, to lakes and water reservoirs in subtropical and temperate zones. These invading species possess traits thought to be common to many invasive organisms: high growth rate, high resource utilization efficiency and overall superior competitive abilities over native species when local conditions vary. Assuming that dispersion routes of cyanobacteria have not been changed much in recent decades, their recent establishment and proliferation in new habitats indicate changes in the environment under which they can exploit their physiological advantage over the native phytoplankton population. In many cases, global warming was identified as the major driving force for the invasion of Nostocales. Due to this uncontrollable trend, invasive Nostocales species are expected to maintain their presence in new habitats and further expand to new environments. In other cases, regional changes in nutrient loads and in biotic conditions were attributed to the invasion events.

  19. Optimal tax progressivity in imperfect labour markets

    DEFF Research Database (Denmark)

    Sørensen, Peter Birch

    1999-01-01

    All modern labour market theories capable of explaining involuntary unemployment as an equilibrium phenomenon imply that increased income tax progressivity reduces unemployment, but they also imply that higher progressivity tends to reduce work effort and labour productivity. This suggests...... progressivity which would maximise the welfare of the representative wage earner. Simulations with these models suggest that the optimal degree of tax progressivity could be quite large, although the results are sensitive to the generosity of unemployment benefits and to the after-tax wage elasticity of work...... that there may be an optimal degree of tax progressivity where the marginal welfare gain from reduced involuntary unemployment is just offset by the marginal welfare loss from lower productivity. This paper sets up four different models of an imperfect labour market in order to identify the degree of tax...

  20. Disease-induced decline of an apex predator drives invasive dominated states and threatens biodiversity.

    Science.gov (United States)

    Hollings, Tracey; Jones, Menna; Mooney, Nick; McCallum, Hamish

    2016-02-01

    Apex predators are important in protecting biodiversity through top-down influence on food webs. Their loss is linked with competitive release of invasive mesopredators and species extinctions. The Tasmanian devil (Sarcophilus harrisii) has experienced severe declines over a 15-yr period as a novel transmissible cancer has spread across its current geographic range. We surveyed the mammalian community, using hair traps, across the spatial extent of the devil's progressive population decline. We found increased activity of alien invasive species (feral cats, black rats), and reduced small and medium-sized native prey species in response to the timing of the decline. In areas of long-term devil decline, invasive species comprised a significantly larger proportion of the community. The results provide evidence that the devil plays a keystone role in Tasmania's ecosystem with their decline linked to a shift toward an invasive state and biodiversity loss in one of Australia's most intact faunal communities.

  1. Non-invasive imaging of atherosclerosis regression with magnetic resonance to guide drug development.

    Science.gov (United States)

    Raggi, Paolo; Baldassarre, Damiano; Day, Simon; de Groot, Eric; Fayad, Z A

    2016-08-01

    Slowing of progression and inducing the regression of atherosclerosis with medical therapy have been shown to be associated with an extensive reduction in risk of cardiovascular events. This proof of concept was obtained with invasive angiographic studies but these are, for obvious reasons, impractical for sequential investigations. Non-invasive imaging has henceforth replaced the more cumbersome invasive studies and has proven extremely valuable in numerous occasions. Because of excellent reproducibility and no radiation exposure, magnetic resonance imaging (MRI) has become the non-invasive method of choice to assess the efficacy of anti-atherosclerotic drugs. The high accuracy of this technology is particularly helpful in rare diseases where the small number of affected patients makes the conduct of outcome-trials in large cohorts impractical. With MRI it is possible to assess the extent, as well as the composition, of atherosclerotic plaques and this further enhances the utility of this technology. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  2. Invasive plant species in hardwood tree plantations

    Science.gov (United States)

    Rochelle R. Beasley; Paula M. Pijut

    2010-01-01

    Invasive plants are species that can grow and spread aggressively, mature quickly, and invade an ecosystem causing economic and environmental damage. Invasive plants usually invade disturbed areas, but can also colonize small areas quickly, and may spread and dominate large areas in a few short years. Invasive plant species displace native or desirable forest...

  3. Invasive plants in 21st Century landscapes.

    Science.gov (United States)

    Valerie. Rapp

    2005-01-01

    A plant species is defined as invasive if it is nonnative to the ecosystem under consideration, and if it causes or is likely to cause economic or environmental harm or harm to human health. Nonnative plant invasions are generally considered to have reached the Pacific Northwest in the mid-1800s with the arrival of European-American settlers. Invasive species such as...

  4. Invasive Species Science Update (No. 9)

    Science.gov (United States)

    Justin Runyon

    2017-01-01

    This newsletter is designed to keep managers and other users up-to-date with recently completed and ongoing research by RMRS scientists, as well as to highlight breaking news related to invasive species issues. The newsletter is produced by the RMRS Invasive Species Working Group (ISWG), a core group of scientists who volunteer to disseminate RMRS invasive species...

  5. Do invasive plant species alter soil health?

    Science.gov (United States)

    Invasive species may alter soil characteristics or interact with the soil microbial community to yield a competitive advantage. Our objectives were to determine: if invasive plant species alter soil properties important to soil health; and the long-term effects of invasive plant species on soil pro...

  6. 78 FR 70317 - Invasive Species Advisory Committee

    Science.gov (United States)

    2013-11-25

    ... DEPARTMENT OF THE INTERIOR Office of the Secretary Invasive Species Advisory Committee AGENCY..., notice is hereby given of meetings of the Invasive Species Advisory Committee. The purpose of the Advisory Committee is to provide advice to the National Invasive Species Council, as authorized by...

  7. Invasive species and climate change (Chapter 7)

    Science.gov (United States)

    Justin B. Runyon; Jack L. Butler; Megan M. Friggens; Susan E. Meyer; Sharlene E. Sing

    2012-01-01

    Invasive species present one of the greatest threats to the health and sustainability of ecosystems worldwide. Invasive plants, animals, and diseases are known to have significant negative effects on biological diversity and the ecological structure and functions of native ecosystems. Moreover, the economic cost imposed by invasive species is enormous—the damage...

  8. Invasive Species Science Update (No. 4)

    Science.gov (United States)

    Ned B. Klopfenstein; Brian W. Geils

    2010-01-01

    The fourth issue of Invasive Species Science Update has finally arrived. This newsletter has no set publication schedule, but our intent is to deliver invasive species information on a timely basis. The RMRS Invasive Species Working Group (ISWG) has been reorganized and recharged. General information on the ISWG is presented in a publication by Butler and others (2009...

  9. Invasive Species Science Update (No. 7)

    Science.gov (United States)

    Dean Pearson; Yvette Ortega; Jack Butler

    2014-01-01

    Invasive Species Science Updates are designed to keep managers and other users up-to-date with recently completed and ongoing research by RMRS scientists, as well as highlight breaking news related to invasive species issues. The newsletter is produced by the RMRS Invasive Species Working Group (ISWG), which is a core group of scientists who volunteer to coordinate...

  10. Invasive Species Science Update (No. 5)

    Science.gov (United States)

    Dean Pearson; Yvette Ortega

    2011-01-01

    Welcome to the fifth issue of the Rocky Mountain Research Station's (RMRS) Invasive Species Science Update. The newsletter is produced by the RMRS Invasive Species Working Group (ISWG), which is a core group of scientists who volunteer to coordinate outreach of RMRS invasive species science to managers and the public. After publishing the past four newsletters, we...

  11. 78 FR 11899 - Invasive Species Advisory Committee

    Science.gov (United States)

    2013-02-20

    ... DEPARTMENT OF THE INTERIOR Office of the Secretary Invasive Species Advisory Committee AGENCY... notice of public meetings of the Invasive Species Advisory Committee. The document contained incorrect..., March 6, 2013; 9 a.m. to 1:45 p.m. Meeting of the Invasive Species Advisory Committee (OPEN): Thursday...

  12. Invasive Species Science Update (No. 8)

    Science.gov (United States)

    Dean Pearson; Yvette Ortega; Jack Butler

    2015-01-01

    Invasive Species Science Updates are designed to keep managers and other users up-to-date with recently completed and ongoing research by RMRS scientists, as well as highlight breaking news related to invasive species issues. The newsletter is produced by the RMRS Invasive Species Working Group (ISWG), which is a core group of scientists who volunteer to coordinate...

  13. Terrestrial animals as invasive species and as species at risk from invasions

    Science.gov (United States)

    Deborah M. Finch; Dean Pearson; Joseph Wunderle; Wayne Arendt

    2010-01-01

    Including terrestrial animal species in the invasive species strategy plan is an important step in invasive species management. Invasions by nonindigenous species threaten nearly 50 percent of imperiled native species in the United States and are the Nation's second leading cause of species endangerment. Invasion and conversion of native habitats by exotic species...

  14. Resource pulses can alleviate the biodiversity-invasion relationship in soil microbial communities.

    Science.gov (United States)

    Mallon, Cyrus A; Poly, Franck; Le Roux, Xavier; Marring, Irene; van Elsas, Jan Dirk; Salles, Joana Falcão

    2015-04-01

    The roles of species richness, resource use, and resource availability are central to many hypotheses explaining the diversity-invasion phenomenon but are generally not investigated together. Here, we created a large diversity gradient of soil microbial communities by either assembling communities of pure bacterial strains or removing the diversity of a natural soil. Using data on the resource-use capacities of the soil communities and an invader that were gathered from 71 carbon sources, we quantified the niches available to both constituents by using the metrics community niche and remaining niche available to the invader. A strong positive relationship between species richness and community niche across both experiments indicated the presence of resource complementarity. Moreover, community niche and the remaining niche available to the invader predicted invader abundance well. This suggested that increased competition in communities of higher diversity limits community invasibility and underscored the importance of resource availability as a key mechanism through which diversity hinders invasions. As a proof of principle, we subjected selected invaded communities to a resource pulse, which progressively uncoupled the link between soil microbial diversity and invasion and allowed the invader to rebound after nearly being eliminated in some communities. Our results thus show that (1) resource competition suppresses invasion, (2) biodiversity increases resource competition and decreases invasion through niche preemption, and (3) resource pulses that cannot be fully used, even by diverse communities, are favorable to invasion.

  15. Progress report 2000

    International Nuclear Information System (INIS)

    2001-01-01

    Clean Air Hamilton is the new name of the Hamilton-Wentworth Air Quality Initiative and its implementation committee, which began in 1995 as a collaborative, multi-sectoral effort to identify and examine important air quality issues and to implement strategies to reduce many of the harmful emissions that endanger human health. During the year 2000 Clean Air Hamilton focused on nine program areas. Strategies were initiated to (1) reduce single occupancy auto trips, (2) purchase low emission vehicles, (3) model transportation emissions, (4) reduce smog-causing emissions, (5) plant trees, (6) provide advice on air quality related land use and transportation issues for consideration in city-wide planning, (7) promote public awareness through social marketing, (8) study fugitive road dust, and (9) reduce transboundary air pollution. A number of indicators to measure progress in efforts to improve air quality have been developed; many of these indicators show significant improvements which, taken collectively, show a positive trend toward cleaner air. The report highlights major accomplishment of Clean Air Hamilton; reports trends in ambient air quality data; assesses human health impacts of air quality, and recommends strategies for further improvements. Among major improvements, inhalable particulate (PM10) levels have decreased by about 20 per cent since 1991; sulphur dioxide levels dropped by 40 per cent since 1989 at industrial sampling sites and 20 per cent at the downtown sampling site; the air pollution index has remained under the advisory level of 32 at all API stations in Hamilton since June 1996. Benzene levels in air decreased by over 50 per cent near the Dofasco plant compared to the five-year composite average from 1994-1998. Given these accomplishments, participants in Clean Air Hamilton believe that while there is much room for improvement, the efforts to date have been worthwhile and provide encouragement for the future. 14 figs., 4 appendices

  16. In situ quantification of genomic instability in breast cancer progression

    Energy Technology Data Exchange (ETDEWEB)

    Ortiz de Solorzano, Carlos; Chin, Koei; Gray, Joe W.; Lockett, Stephen J.

    2003-05-15

    Genomic instability is a hallmark of breast and other solid cancers. Presumably caused by critical telomere reduction, GI is responsible for providing the genetic diversity required in the multi-step progression of the disease. We have used multicolor fluorescence in situ hybridization and 3D image analysis to quantify genomic instability cell-by-cell in thick, intact tissue sections of normal breast epithelium, preneoplastic lesions (usual ductal hyperplasia), ductal carcinona is situ or invasive carcinoma of the breast. Our in situ-cell by cell-analysis of genomic instability shows an important increase of genomic instability in the transition from hyperplasia to in situ carcinoma, followed by a reduction of instability in invasive carcinoma. This pattern suggests that the transition from hyperplasia to in situ carcinoma corresponds to telomere crisis and invasive carcinoma is a consequence of telomerase reactivation afertelomere crisis.

  17. Post-operative radiotherapy in invasive thymoma

    International Nuclear Information System (INIS)

    Jackson, M.A.; Ball, D.L.

    1991-01-01

    The experience of a large Cancer Institute in treating invasive thymoma has been reviewed. Twenty-eight patients received radiotherapy following biopsy or incomplete resection of thymoma. The overall survival was 53 percent at 5 years and 44 percent at 10 years. Treatment was generally well tolerated but 3 patients (11 percent) developed significant side effects from the radiotherapy and two of these died. Radiotherapy appeared to be more effective in patients who had a small volume of residual disease after surgery. An attempt was made to identify prognostic factors but none reached statistical significance. The radiation dose, field size and the use of systemic treatment are discussed. (author). 26 refs.; 2 figs.; 3 tabs

  18. Optimal tax progressivity in imperfect labour markets

    DEFF Research Database (Denmark)

    Sørensen, Peter Birch

    1999-01-01

    All modern labour market theories capable of explaining involuntary unemployment as an equilibrium phenomenon imply that increased income tax progressivity reduces unemployment, but they also imply that higher progressivity tends to reduce work effort and labour productivity. This suggests...... that there may be an optimal degree of tax progressivity where the marginal welfare gain from reduced involuntary unemployment is just offset by the marginal welfare loss from lower productivity. This paper sets up four different models of an imperfect labour market in order to identify the degree of tax...

  19. Invasive procedures with questionable indications

    Directory of Open Access Journals (Sweden)

    Sergei V. Jargin

    2014-12-01

    Full Text Available Insufficient coordination of medical research and partial isolation from the international scientific community can result in application of invasive methods without sufficient indications. Here is presented an overview of renal and pancreatic biopsy studies performed in the course of the operations of pancreatic blood shunting into the systemic blood flow in type 1 diabetic patients. Furthermore a surgical procedure of lung denervation as a treatment method of asthma as well as the use of bronchoscopy for research in asthmatics are discussed here. Today, the upturn in Russian economy enables acquisition of modern equipment; and medical research is on the increase. Under these circumstances, the purpose of this letter was to remind that, performing surgical or other invasive procedures, the risk-to-benefit ratio should be kept as low as possible.

  20. Effect of Age on Outcome of High-Risk Non-Muscle-Invasive Bladder Cancer Patients Treated with Second Transurethral Resection and Maintenance Bacillus Calmette-Guerin Therapy

    Directory of Open Access Journals (Sweden)

    Sümer Baltacı

    2016-09-01

    Full Text Available Objective To determine the effect of age on recurrence and progression rates in a population of high-risk non-muscle invasive bladder cancer (NMIBC patients treated with a second transurethral resection (TUR and at least 1 year of maintenance Bacillus Calmette-Guerin (BCG therapy. Materials and Methods In this multicenter study, we reviewed the data of patients treated for high-risk NMIBC between 2005 and 2012. Patients without a muscle-invasive cancer on second TUR and received induction BCG and at least one year of maintenance BCG therapy and at least 12 months of follow-up after completion of maintenance BCG were included. Effect of age was analyzed both dichotomously (<70 or ≥70 years as well as by 10-year increments. Chi-square test, Student’s T-test and analysis of variance (ANOVA were used for comparison of the groups. Univariate and multivariate logistic regression analyses were performed to identify predictors of recurrence and progression. Results Overall, 242 eligible patients were included. Baseline parameters were similar. With a mean follow-up of 29.4±22.2 months, neither 3-year recurrence-free survival nor 3-year progression-free survival differed between the age groups when examined either dichotomously or by 10-year increments. Conclusion In high-risk NMIBC patients treated with a second TUR and received maintenance BCG therapy, age was not associated with increased rates of neither recurrence nor progression. Until a randomized prospective clinical trial assess the appropriate adjuvant intravesical therapy in the elderly, elderly patients should probably be treated in the same manner as younger patients.

  1. Nietzsche, Pragmatism, and Progress

    OpenAIRE

    Harris, Daniel

    2010-01-01

    In this paper I argue that in Richard Rorty’s pragmatism we find a view of political progress at once at home in Nietzsche’s thought and in the Enlightenment tradition. If we think of progress as indexed to some permanent standard, and then agree that it is Nietzsche who dispels the authority of any such standard, then we may perhaps conclude that after Nietzsche, progress is ruled out. I want to show, however, that we find in Nietzsche comfort for a continued vision of human prog...

  2. Internationalisering og progression

    DEFF Research Database (Denmark)

    Wilken, Lisanne; Tange, Hanne

    2014-01-01

    education followed by two years of specialization within the same discipline. This idea is now being challenged on several fronts. For instance, it is becoming more common for Danish universities to offer interdisciplinary master programs. Also, the trend for greater internationalization in higher education...... sig til progression. Artiklen er skrevet på baggrund af semistrukturerede interviews med undervisere fra tværfaglige, internationale uddannelser ved Aarhus Universitet. University programs in Denmark have traditionally been perceived as a continuous education consisting of three years of basic...... universities reflect on progression in education. The article distinguishes between different forms of progression....

  3. Progress test utopia.

    Science.gov (United States)

    van der Vleuten, Cees; Freeman, Adrian; Collares, Carlos Fernando

    2018-04-01

    This paper discusses the advantages of progress testing. A utopia is described where medical schools would work together to develop and administer progress testing. This would lead to a significant reduction of cost, an increase in the quality of measurement and phenomenal feedback to learner and school. Progress testing would also provide more freedom and resources for more creative in-school assessment. It would be an educationally attractive alternative for the creation of cognitive licensing exams. A utopia is always far away in the future, but by formulating a vision for that future we may engage in discussions on how to get there.

  4. Radiologic aspects in invasive aspergillosis

    International Nuclear Information System (INIS)

    Feger, C.; Kerviler, E. de; Zagdanski, A.M.; Attal, P.; Cyna-Gorse, F.; Frija, J.; Laval-Jeantet, M.

    1994-01-01

    Invasive aspergillosis is a life-threatening illness, whose diagnosis is difficult: clinical signs are indeed not specific, and biological and mycological exams are not always conclusive. Radiological exams are essential for the diagnosis of this disease allowing to start an early intensive appropriate therapy. According to the literature and to their own experience the authors report the main radiological patterns with emphasis on the pulmonary and cerebral affections. (authors). 26 refs., 5 figs

  5. Non-invasive extending prosthesis

    OpenAIRE

    Meswania, Jayantilal Mohanlal

    2006-01-01

    Most sarcomas of the bone occur in patients of a relatively young age including skeletally immature patients. Approximately 50 child sarcomas are treated with limb salvage surgery per year in the United Kingdom. These children need an extendible implant that can be lengthened periodically to keep pace with the growth in the opposite limb. Surgically, invasive devices have been used for the past thirty years with intrinsic problems of infection and long-term recurrent trauma to the patient. To...

  6. Biological invasions, ecological resilience and adaptive governance

    Science.gov (United States)

    Chaffin, Brian C.; Garmestani, Ahjond S.; Angeler, David G.; Herrmann, Dustin L.; Stow, Craig A.; Nystrom, Magnus; Sendzimir, Jan; Hopton, Matthew E.; Kolasa, Jurek; Allen, Craig R.

    2016-01-01

    In a world of increasing interconnections in global trade as well as rapid change in climate and land cover, the accelerating introduction and spread of invasive species is a critical concern due to associated negative social and ecological impacts, both real and perceived. Much of the societal response to invasive species to date has been associated with negative economic consequences of invasions. This response has shaped a war-like approach to addressing invasions, one with an agenda of eradications and intense ecological restoration efforts towards prior or more desirable ecological regimes. This trajectory often ignores the concept of ecological resilience and associated approaches of resilience-based governance. We argue that the relationship between ecological resilience and invasive species has been understudied to the detriment of attempts to govern invasions, and that most management actions fail, primarily because they do not incorporate adaptive, learning-based approaches. Invasive species can decrease resilience by reducing the biodiversity that underpins ecological functions and processes, making ecosystems more prone to regime shifts. However, invasions do not always result in a shift to an alternative regime; invasions can also increase resilience by introducing novelty, replacing lost ecological functions or adding redundancy that strengthens already existing structures and processes in an ecosystem. This paper examines the potential impacts of species invasions on the resilience of ecosystems and suggests that resilience-based approaches can inform policy by linking the governance of biological invasions to the negotiation of tradeoffs between ecosystem services.

  7. Inhibition of RUNX2 transcriptional activity blocks the proliferation, migration and invasion of epithelial ovarian carcinoma cells.

    Directory of Open Access Journals (Sweden)

    Zhi-Qiang Wang

    Full Text Available Previously, we have identified the RUNX2 gene as hypomethylated and overexpressed in post-chemotherapy (CT primary cultures derived from serous epithelial ovarian cancer (EOC patients, when compared to primary cultures derived from matched primary (prior to CT tumors. However, we found no differences in the RUNX2 methylation in primary EOC tumors and EOC omental metastases, suggesting that DNA methylation-based epigenetic mechanisms have no impact on RUNX2 expression in advanced (metastatic stage of the disease. Moreover, RUNX2 displayed significantly higher expression not only in metastatic tissue, but also in high-grade primary tumors and even in low malignant potential tumors. Knockdown of the RUNX2 expression in EOC cells led to a sharp decrease of cell proliferation and significantly inhibited EOC cell migration and invasion. Gene expression profiling and consecutive network and pathway analyses confirmed these findings, as various genes and pathways known previously to be implicated in ovarian tumorigenesis, including EOC tumor invasion and metastasis, were found to be downregulated upon RUNX2 suppression, while a number of pro-apoptotic genes and some EOC tumor suppressor genes were induced. Taken together, our data are indicative for a strong oncogenic potential of the RUNX2 gene in serous EOC progression and suggest that RUNX2 might be a novel EOC therapeutic target. Further studies are needed to more completely elucidate the functional implications of RUNX2 and other members of the RUNX gene family in ovarian tumorigenesis.

  8. MiR-613 suppresses retinoblastoma cell proliferation, invasion, and tumor formation by targeting E2F5.

    Science.gov (United States)

    Zhang, Yiting; Zhu, Xinyue; Zhu, Xiaomin; Wu, Yan; Liu, Yajun; Yao, Borui; Huang, Zhenping

    2017-03-01

    Retinoblastoma is a common intraocular malignancy that occurs during childhood. MicroRNAs play critical roles in the regulation of retinoblastoma initiation and progression, and aberrant expression of miR-613 had been reported in various types of cancer. However, the role and mechanism of its function in retinoblastoma are still unclear. In this study, we found that miR-613 was downregulated in retinoblastoma tissues and cell lines. Overexpression of miR-613 suppressed retinoblastoma cell proliferation, migration, and invasion and induced cell cycle arrest in vitro. Additionally, overexpressed miR-613 also inhibited tumor formation of retinoblastoma cells in vivo. We further identified E2F5 as a direct target of miR-613. Reintroduction of E2F5 without 3'-untranslated region reversed the inhibitory effects of miR-613 on cell proliferation and invasion. Our data collectively indicate that miR-613 functions as a tumor suppressor in retinoblastoma through downregulating E2F5, supporting the targeting of the novel miR-613/E2F5 axis as a potentially effective therapeutic approach for retinoblastoma.

  9. Up-regulation of hepatoma-derived growth factor facilitates tumor progression in malignant melanoma [corrected].

    Directory of Open Access Journals (Sweden)

    Han-En Tsai

    Full Text Available Cutaneous malignant melanoma is the fastest increasing malignancy in humans. Hepatoma-derived growth factor (HDGF is a novel growth factor identified from human hepatoma cell line. HDGF overexpression is correlated with poor prognosis in various types of cancer including melanoma. However, the underlying mechanism of HDGF overexpression in developing melanoma remains unclear. In this study, human melanoma cell lines (A375, A2058, MEL-RM and MM200 showed higher levels of HDGF gene expression, whereas human epidermal melanocytes (HEMn expressed less. Exogenous application of HDGF stimulated colony formation and invasion of human melanoma cells. Moreover, HDGF overexpression stimulated the degree of invasion and colony formation of B16-F10 melanoma cells whereas HDGF knockdown exerted opposite effects in vitro. To evaluate the effects of HDGF on tumour growth and metastasis in vivo, syngeneic mouse melanoma and metastatic melanoma models were performed by manipulating the gene expression of HDGF in melanoma cells. It was found that mice injected with HDGF-overexpressing melanoma cells had greater tumour growth and higher metastatic capability. In contrast, mice implanted with HDGF-depleted melanoma cells exhibited reduced tumor burden and lung metastasis. Histological analysis of excised tumors revealed higher degree of cell proliferation and neovascularization in HDGF-overexpressing melanoma. The present study provides evidence that HDGF promotes tumor progression of melanoma and targeting HDGF may constitute a novel strategy for the treatment of melanoma.

  10. Up-Regulation of Hepatoma-Derived Growth Factor Facilities Tumor Progression in Malignant Melanoma

    Science.gov (United States)

    Kung, Mei-Lang; Liu, Li-Feng; Kuo, Lai-Hsin; Kuo, Hsiao-Mei; Chen, San-Cher; Chan, Elsa C.; Wu, Chieh-Shan; Tai, Ming-Hong; Liu, Guei-Sheung

    2013-01-01

    Cutaneous malignant melanoma is the fastest increasing malignancy in humans. Hepatoma-derived growth factor (HDGF) is a novel growth factor identified from human hepatoma cell line. HDGF overexpression is correlated with poor prognosis in various types of cancer including melanoma. However, the underlying mechanism of HDGF overexpression in developing melanoma remains unclear. In this study, human melanoma cell lines (A375, A2058, MEL-RM and MM200) showed higher levels of HDGF gene expression, whereas human epidermal melanocytes (HEMn) expressed less. Exogenous application of HDGF stimulated colony formation and invasion of human melanoma cells. Moreover, HDGF overexpression stimulated the degree of invasion and colony formation of B16–F10 melanoma cells whereas HDGF knockdown exerted opposite effects in vitro. To evaluate the effects of HDGF on tumour growth and metastasis in vivo, syngeneic mouse melanoma and metastatic melanoma models were performed by manipulating the gene expression of HDGF in melanoma cells. It was found that mice injected with HDGF-overexpressing melanoma cells had greater tumour growth and higher metastatic capability. In contrast, mice implanted with HDGF-depleted melanoma cells exhibited reduced tumor burden and lung metastasis. Histological analysis of excised tumors revealed higher degree of cell proliferation and neovascularization in HDGF-overexpressing melanoma. The present study provides evidence that HDGF promotes tumor progression of melanoma and targeting HDGF may constitute a novel strategy for the treatment of melanoma. PMID:23536873

  11. Invasive predators and global biodiversity loss.

    Science.gov (United States)

    Doherty, Tim S; Glen, Alistair S; Nimmo, Dale G; Ritchie, Euan G; Dickman, Chris R

    2016-10-04

    Invasive species threaten biodiversity globally, and invasive mammalian predators are particularly damaging, having contributed to considerable species decline and extinction. We provide a global metaanalysis of these impacts and reveal their full extent. Invasive predators are implicated in 87 bird, 45 mammal, and 10 reptile species extinctions-58% of these groups' contemporary extinctions worldwide. These figures are likely underestimated because 23 critically endangered species that we assessed are classed as "possibly extinct." Invasive mammalian predators endanger a further 596 species at risk of extinction, with cats, rodents, dogs, and pigs threatening the most species overall. Species most at risk from predators have high evolutionary distinctiveness and inhabit insular environments. Invasive mammalian predators are therefore important drivers of irreversible loss of phylogenetic diversity worldwide. That most impacted species are insular indicates that management of invasive predators on islands should be a global conservation priority. Understanding and mitigating the impact of invasive mammalian predators is essential for reducing the rate of global biodiversity loss.

  12. Physicians’ Progress Notes

    DEFF Research Database (Denmark)

    Bansler, Jørgen; Havn, Erling C.; Mønsted, Troels

    2013-01-01

    This paper examines physicians’ progress notes, an artifact that, in spite of its obvious importance in the coordination of cooperative work in clinical settings, has not been subjected to systematic study under CSCW auspices. While several studies have addressed the role of the medical record...... in patient care, they have not dealt specifically with the role, structure, and content of the progress notes. As a consequence, CSCW research has not yet taken fully into account the fact that progress notes are coordinative artifacts of a rather special kind, an open-ended chain of prose texts, written...... sequentially by cooperating physicians for their own use as well as for that of their colleagues. We argue that progress notes are the core of the medical record, in that they marshal and summarize the overwhelming amount of data that is available in the modern hospital environment, and that their narrative...

  13. Progress report 1985

    International Nuclear Information System (INIS)

    1986-01-01

    This progress report of the nuclear physics institute includes five basic subjects: theoretical physics, high energy and intermediate energy physics, nuclear physics, combined research physics and instrumentation (microelectronics, imaging, multidetectors, scintillators,...) [fr

  14. Progress for the Paralyzed

    Science.gov (United States)

    ... Contents Latest Advances Help People Regain Function and Independence Founded in 2000, the National Institute for Biomedical ... More "NIBIB Robotics" Articles Progress for the Paralyzed / College Athlete Stands Again…On His Own! / Coffee to ...

  15. Progress report 1979

    International Nuclear Information System (INIS)

    1979-01-01

    Progress report on the meetings and working groups of DAF in 1979, e.g. engineering and industry, public and press, law and administration, business and industry, international cooperation in Europe and with the USA. (GL) [de

  16. Progress report, Physics Division

    International Nuclear Information System (INIS)

    1986-03-01

    This report reviews events and progress in the following areas: development of the TASCC facility; experimental and theoretical nuclear physics research; radionuclide standardization; condensed matter research; applied mathematics; and computer facility operation

  17. Progression of Liver Disease

    Science.gov (United States)

    ... Legacy Society Make Gifts of Stock Donate Your Car Personal Fundraising Partnership & Support Share Your Story Spread the Word Give While You Shop Contact Us Donate Now The Progression of Liver ...

  18. Dynamic expression patterns of differential proteins during early invasion of hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Rong-Xin Chen

    Full Text Available Tumor cell invasion into the surrounding matrix has been well documented as an early event of metastasis occurrence. However, the dynamic expression patterns of proteins during early invasion of hepatocellular carcinoma (HCC are largely unknown. Using a three-dimensional HCC invasion culture model established previously, we investigated the dynamic expression patterns of identified proteins during early invasion of HCC.Highly metastatic MHCC97H cells and a liver tissue fragment were long-term co-cultured in a rotating wall vessel (RWV bioreactor to simulate different pathological states of HCC invasion. The established spherical co-cultures were collected on days 0, 5, 10, and 15 for dynamic expression pattern analysis. Significantly different proteins among spheroids at different time points were screened and identified using quantitative proteomics of iTRAQ labeling coupled with LC-MS/MS. Dynamic expression patterns of differential proteins were further categorized by K-means clustering. The expression modes of several differentially expressed proteins were confirmed by Western blot and qRT-PCR.Time course analysis of invasion/metastasis gene expressions (MMP2, MMP7, MMP9, CD44, SPP1, CXCR4, CXCL12, and CDH1 showed remarkable, dynamic alterations during the invasion process of HCC. A total of 1,028 proteins were identified in spherical co-cultures collected at different time points by quantitative proteomics. Among these proteins, 529 common differential proteins related to HCC invasion were clustered into 25 types of expression patterns. Some proteins displayed significant dynamic alterations during the early invasion process of HCC, such as upregulation at the early invasion stage and downregulation at the late invasion stage (e.g., MAPRE1, PHB2, cathepsin D, etc. or continuous upregulation during the entire invasion process (e.g., vitronectin, Met, clusterin, ICAM1, GSN, etc..Dynamic expression patterns of candidate proteins during the

  19. 3D-CRT, Proton, or Brachytherapy APBI in Treating Patients With Invasive and Non-invasive Breast Cancer

    Science.gov (United States)

    2017-12-29

    Ductal Breast Carcinoma In Situ; Estrogen Receptor Positive; Grade 1 Invasive Breast Carcinoma; Grade 2 Invasive Breast Carcinoma; Grade 3 Invasive Breast Carcinoma; Invasive Ductal and Lobular Carcinoma In Situ; Mucinous Breast Carcinoma; Tubular Breast Carcinoma

  20. Progressive supranuclear palsy: new concepts

    Directory of Open Access Journals (Sweden)

    Orlando Graziani Povoas Barsottini

    2010-12-01

    Full Text Available Progressive supranuclear palsy (PSP is a distinctive form of neurodegenerative disease which affects the brainstem and basal ganglia. Patients present supranuclear ophthalmoplegia, postural instability and mild dementia. PSP is defined neuropathologically by the accumulation of neurofibrillary tangles in the subthalamic nucleus, pallidum, red nucleus, substantia nigra, striatum, pontine tegmentum, oculomotor nucleus, medulla and dentate nucleus. Over the last decade many lines of investigations have helped refine PSP in many aspects and it is the purpose of this review to help neurologists identify PSP, to better understand its pathophysiology and to provide a more focused, symptom-based treatment approach.