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Sample records for cancer tracer synthesis

  1. Microfluidics for Synthesis of Peptide-Based PET Tracers

    Directory of Open Access Journals (Sweden)

    Yang Liu

    2013-01-01

    Full Text Available Positron emission tomography (PET is a powerful noninvasive tool for acquisition of the physiological parameters in human and animals with the help of PET tracers. Among all the PET tracers, radiolabeled peptides have been widely explored for cancer-related receptor imaging due to their high affinity and specificity to receptors. But radiochemistry procedures for production of peptide-based PET tracers are usually complex, which makes large-scale clinical studies relatively challenging. New radiolabeling technologies which could simplify synthesis and purification procedures, are extremely needed. Over the last decade, microfluidics and lab-on-a-chip (LOC technology have boomed as powerful tools in the field of organic chemistry, which potentially provide significant help to the PET chemistry. In this minireview, microfluidic radiolabeling technology is described and its application for synthesis of peptide-based PET tracers is summarized and discussed.

  2. Synthesis and characterization of environmentally friendly fluorescent particle tracers

    Science.gov (United States)

    Tauro, Flavia; Porfiri, Maurizio; Rapiti, Emiliano; Grimaldi, Salvatore

    2013-04-01

    Tracers are widely used in experimental fluid mechanics and hydrology to investigate complex flows and water cycle processes. Commonly used tracers include dyes, artificial tracers, naturally occurring isotopes and chemicals, microorganisms, and DNA-based systems. Tracers should be characterized by low detection limits and high accuracy in following water paths and flow structures. For natural studies, tracers are also expected to be nontoxic and with low sorption affinity to natural substrates to minimize losses in the environment. In this context, while isotopes are completely natural, their use in field studies is limited by their ubiquity and, therefore, by the high uncertainty in data processing methodologies. Further, the use of dyes and artificial tracers can be hampered by extremely low detection limits due to dilution in natural streams and microorganisms, while DNA-based system may require physical sampling and time-consuming functionalization and detection procedures. In this work, we present the synthesis and characterization of fluorescent beads incorporating an eco-compatible fluorophore for environmental and laboratory applications. The particles are synthesized from natural beeswax through an inexpensive thermal procedure and can be engineered to present variable densities and diameters. A thorough characterization of their surface morphology at the nanoscale, crystal structure and size, chemical composition, and dye incorporation into the beeswax matrix is described by using a wide array of microscopy techniques. In addition, the particle fluorescence response is studied by performing excitation and emission scans on melted beeswax bead samples. The feasibility of using the synthesized particles in environmental settings is assessed through the design of ad-hoc weathering agent experiments where the beads are exposed to high energy radiation and hot water. Further, a proof of concept test is described to understand the particles' potential as a

  3. Measuring serotonin synthesis: from conventional methods to PET tracers and their (pre)clinical implications

    Energy Technology Data Exchange (ETDEWEB)

    Visser, Anniek K.D.; Waarde, Aren van; Willemsen, Antoon T.M. [University of Groningen, University Medical Center Groningen, Department of Nuclear Medicine and Molecular Imaging, Groningen (Netherlands); Bosker, Fokko J. [University of Groningen, University Medical Center Groningen, University Center of Psychiatry, Groningen (Netherlands); Luiten, Paul G.M. [University of Groningen, Center for Behavior and Neurosciences, Department of Molecular Neurobiology, Haren (Netherlands); Boer, Johan A. den [University of Groningen, University Medical Center Groningen, Department of Nuclear Medicine and Molecular Imaging, Groningen (Netherlands); University of Groningen, University Medical Center Groningen, University Center of Psychiatry, Groningen (Netherlands); Kema, Ido P. [University of Groningen, University Medical Center Groningen, Department of Laboratory Medicine, Groningen (Netherlands); Dierckx, Rudi A.J.O. [University of Groningen, University Medical Center Groningen, Department of Nuclear Medicine and Molecular Imaging, Groningen (Netherlands); University Hospital Ghent, Department of Nuclear Medicine, Ghent (Belgium)

    2011-03-15

    The serotonergic system of the brain is complex, with an extensive innervation pattern covering all brain regions and endowed with at least 15 different receptors (each with their particular distribution patterns), specific reuptake mechanisms and synthetic processes. Many aspects of the functioning of the serotonergic system are still unclear, partially because of the difficulty of measuring physiological processes in the living brain. In this review we give an overview of the conventional methods of measuring serotonin synthesis and methods using positron emission tomography (PET) tracers, more specifically with respect to serotonergic function in affective disorders. Conventional methods are invasive and do not directly measure synthesis rates. Although they may give insight into turnover rates, a more direct measurement may be preferred. PET is a noninvasive technique which can trace metabolic processes, like serotonin synthesis. Tracers developed for this purpose are {alpha}-[{sup 11}C]methyltryptophan ([{sup 11}C]AMT) and 5-hydroxy-L-[{beta}-{sup 11}C]tryptophan ([{sup 11}C]5-HTP). Both tracers have advantages and disadvantages. [{sup 11}C]AMT can enter the kynurenine pathway under inflammatory conditions (and thus provide a false signal), but this tracer has been used in many studies leading to novel insights regarding antidepressant action. [{sup 11}C]5-HTP is difficult to produce, but trapping of this compound may better represent serotonin synthesis. AMT and 5-HTP kinetics are differently affected by tryptophan depletion and changes of mood. This may indicate that both tracers are associated with different enzymatic processes. In conclusion, PET with radiolabelled substrates for the serotonergic pathway is the only direct way to detect changes of serotonin synthesis in the living brain. (orig.)

  4. Double-tracer autoradiographic study of protein synthesis and glucose consumption in rats with focal cerebral ischemia

    DEFF Research Database (Denmark)

    Christensen, Thomas; Balchen, T; Bruhn, T;

    1999-01-01

    A double-tracer autoradiographic method for simultaneous measurement of regional glucose utilization (rCMRglc) and regional protein synthesis (PS) in consecutive brain sections is described and applied to study the metabolism of the ischemic penumbra 2 h after occlusion of the middle cerebral...

  5. Isotopic tracer studies of Fischer-Tropsch Synthesis over Ru/TiO sub 2 catalysts

    Energy Technology Data Exchange (ETDEWEB)

    Krishna, K.R.

    1992-01-01

    Fischer-Tropsch synthesis is a process in which CO and H{sub 2} react to give predominantly liquid hydrocarbons. The reaction can be considered a special type of polymerization in which the monomer is produced in situ, and chain growth occurs by a sequence of independently repeated additions of the monomer to the growing chain. A investigation has been conducted to study the CO hydrogenation reaction in order to better understand catalyst deactivation and the elementary surface processes involved in chain growth. Isotopic tracers are used in conjunction with transient-response techniques in this study of Fischer-Tropsch synthesis over Ru/TiO{sub 2} catalysts. Experiments are conducted at a total pressure of 1 atmosphere, reaction temperatures of 453--498 K and D{sub 2}/CO (or H{sub 2}/CO) ratios of 2--5. Synthesis products are analyzed by gas chromatography or isotope-ratio gas chromatography-mass spectrometry. Rate constants for chain initiation, propagation and termination are evaluated under steady-state reaction conditions by using transients in isotopic composition. The activation energy for chain termination is much higher than that for propagation, accounting for the observed decrease in the chain growth parameter are also estimated. Coverages by reaction intermediates are also estimated. When small amounts of {sup 12}C-labelled ethylene are added to {sup 13}CO/H{sub 2} synthesis gas, ethylene acts as the sole chain initiator. Ethylene-derived carbon also accounts for 45% of the C{sub 1} monomer pool. 102 refs., 29 figs., 11 tabs.

  6. Isotopic tracer studies of Fischer-Tropsch Synthesis over Ru/TiO{sub 2} catalysts

    Energy Technology Data Exchange (ETDEWEB)

    Krishna, K.R.

    1992-01-01

    Fischer-Tropsch synthesis is a process in which CO and H{sub 2} react to give predominantly liquid hydrocarbons. The reaction can be considered a special type of polymerization in which the monomer is produced in situ, and chain growth occurs by a sequence of independently repeated additions of the monomer to the growing chain. A investigation has been conducted to study the CO hydrogenation reaction in order to better understand catalyst deactivation and the elementary surface processes involved in chain growth. Isotopic tracers are used in conjunction with transient-response techniques in this study of Fischer-Tropsch synthesis over Ru/TiO{sub 2} catalysts. Experiments are conducted at a total pressure of 1 atmosphere, reaction temperatures of 453--498 K and D{sub 2}/CO (or H{sub 2}/CO) ratios of 2--5. Synthesis products are analyzed by gas chromatography or isotope-ratio gas chromatography-mass spectrometry. Rate constants for chain initiation, propagation and termination are evaluated under steady-state reaction conditions by using transients in isotopic composition. The activation energy for chain termination is much higher than that for propagation, accounting for the observed decrease in the chain growth parameter are also estimated. Coverages by reaction intermediates are also estimated. When small amounts of {sup 12}C-labelled ethylene are added to {sup 13}CO/H{sub 2} synthesis gas, ethylene acts as the sole chain initiator. Ethylene-derived carbon also accounts for 45% of the C{sub 1} monomer pool. 102 refs., 29 figs., 11 tabs.

  7. 11C-harmine as a potential PET tracer for ductal pancreas cancer: in vitro studies.

    Science.gov (United States)

    Herlin, G; Persson, B; Bergström, M; Långström, B; Aspelin, P

    2003-04-01

    Our objective was to find a tracer in diagnosing human pancreatic cancer using positron emission tomography (PET). For this purpose in vitro test of pancreatic tissues with autoradiography was used. Autoradiography was performed with (11)C-harmine (a MAO-A-inhibitor) with and without competitive inhibition. Tissue preparations were obtained from normal human pancreas and pancreatic cancer. The uptake was compared with rat brain or pig brain, tissues with high expression of MAO-A. Nine autoradiography studies on 16 samples from five different human pancreatic cancers gave a significant level of specific binding of (11)C-harmine in 13, and 3 samples did not give a significant level of specific binding of (11)C-harmine. All 16 samples were analysed with autoradiography. Compared with rat brain, the uptake in the human cancers varied between 9 and 43% except for one tissue preparation which had a too low value for measurement. This study shows expression of MAO-A in human pancreatic cancer. This is readily characterised in vitro. The potential use of (11)C-harmine in the diagnosis of pancreatic cancer using PET might be limited, but further PET studies are necessary.

  8. Comparative performance of PET tracers in biochemical recurrence of prostate cancer: a critical analysis of literature.

    Science.gov (United States)

    Yu, Chung Yao; Desai, Bhushan; Ji, Lingyun; Groshen, Susan; Jadvar, Hossein

    2014-01-01

    Positron emission tomography (PET) with a number of tracers targeted to particular biological features of cancer has been explored for the imaging evaluation of patients with biochemical recurrence of prostate cancer after curative primary treatment. However, these reports are often heterogeneous in study design, patient cohorts, standards of reference for the imaging findings, data analysis, and data reporting. The aim of our study was to address these limitations by extracting and re-analyzing the PET detection data only from studies that satisfied pre-defined sets of patient selection criteria and verification standards. Our investigation analyzed the effects of 5 tracers ((18)F-fluorodeoxyglucose (FDG), (11)C-acetate (ACET), (11)C- or (18)F-choline (CHOL), anti-1-amino-3-(18)F-fluorocyclobutane-1-carboxylic acid (FACBC), and radiolabeled ligand targeted to prostate-specific membrane antigen (PSMA)), 2 treatment types (radical prostatectomy and radiation therapy), and whether the detected disease was local or metastatic, including lesion type (bone, lymph node, soft tissue). FDG exhibited the lowest detection rate for any suspected disease. ACET tended to be advantageous over CHOL in detecting local recurrence and lymph node lesions, even though the difference was not statistically significant. FACBC had greater likelihood of detecting local recurrence, when compared to CHOL, though this difference was not statistically significant. PSMA tended to show a higher proportion of patients with suspected disease compared to the other four tracers. Patients treated with radiation therapy had greater odds of displaying local recurrence on PET than those treated with radical prostatectomy. We also provide suggestions for future investigations that facilitate communication and the impact of the findings.

  9. Comparison of radioactive tracer tin colloid and phytate for sentinel node biopsy in breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yagata, Hiroshi; Suzuki, Masato; Nagashima, Takashi; Kasagawa, Takahiro; Sakakibara, Masahiro; Oshida, Keiko; Sangai, Takafumi; Nakano, S.; Miyazaki, Masaru [Chiba Univ. (Japan). Graduate School of Medicine

    2002-10-01

    Eighty-four consecutive sentinel node biopsies were performed using dye and radioactive tracer (tin colloid for 42 tumors and phytate for 42 tumors). They had subdermal injection on the morning of surgery or the afternoon before surgery. Maximum RI count of each sentinel node was recorded and classified {<=}5 counts per second (cps), 5-20, or 20<. In injection on the afternoon before surgery, 19 tumors had {<=}5 cps and 2 had 20 cps< in 24 of tin colloid, whereas 1 had {<=}5 cps and 18 had 20 cps< in 22 of phytate. In injection on the morning of surgery, 9 had {<=}5 and 20 had 20< in 18 of tin colloid, whereas 1 had {<=}5 and 18 had 20< in 20 of phytate. The injection of phytate tended to have higher RI count than tin colloid. Phytate is superior to tin colloid for sentinel node biopsy in breast cancer. (author)

  10. Development of a New Positron Emission Tomography Tracer for Targeting Tumor Angiogenesis: Synthesis, Small Animal Imaging, and Radiation Dosimetry

    Directory of Open Access Journals (Sweden)

    David S. Lalush

    2013-05-01

    Full Text Available Angiogenesis plays a key role in cancer progression and correlates with disease aggressiveness and poor clinical outcomes. Affinity ligands discovered by screening phage display random peptide libraries can be engineered to molecularly target tumor blood vessels for noninvasive imaging and early detection of tumor aggressiveness. In this study, we tested the ability of a phage-display-selected peptide sequence recognizing specifically bone marrow- derived pro-angiogenic tumor-homing cells, the QFP-peptide, radiolabeled with 64Cu radioisotope to selectively image tumor vasculature in vivo by positron emission tomography (PET. To prepare the targeted PET tracer we modified QFP-phage with the DOTA chelator and radiolabeled the purified QFP-phage-DOTA intermediate with 64Cu to obtain QFP-targeted radioconjugate with high radiopharmaceutical yield and specific activity. We evaluated the new PET tracer in vivo in a subcutaneous (s.c. Lewis lung carcinoma (LLC mouse model and conducted tissue distribution, small animal PET/CT imaging study, autoradiography, histology, fluorescence imaging, and dosimetry assessments. The results from this study show that, in the context of the s.c. LLC immunocompetent mouse model, the QFP-tracer can target tumor blood vessels selectively. However, further optimization of the biodistribution and dosimetry profile of the tracer is necessary to ensure efficient radiopharmaceutical applications enabled by the biological specificity of the QFP-peptide.

  11. Multi-contrast attenuation map synthesis for PET/MR scanners: assessment on FDG and Florbetapir PET tracers

    Energy Technology Data Exchange (ETDEWEB)

    Burgos, Ninon [University College London, Translational Imaging Group, Centre for Medical Image Computing, London (United Kingdom); Cardoso, M.J.; Modat, Marc; Ourselin, Sebastien [University College London, Translational Imaging Group, Centre for Medical Image Computing, London (United Kingdom); University College London, Dementia Research Centre, Institute of Neurology, London (United Kingdom); Thielemans, Kris; Dickson, John [University College London, Institute of Nuclear Medicine, London (United Kingdom); Schott, Jonathan M. [University College London, Dementia Research Centre, Institute of Neurology, London (United Kingdom); Atkinson, David [University College London, Centre for Medical Imaging, London (United Kingdom); Arridge, Simon R. [University College London, Centre for Medical Image Computing, London (United Kingdom); Hutton, Brian F. [University College London, Institute of Nuclear Medicine, London (United Kingdom); University of Wollongong, Centre for Medical Radiation Physics, Wollongong, NSW (Australia)

    2015-08-15

    Positron Emission Tomography/Magnetic Resonance Imaging (PET/MR) scanners are expected to offer a new range of clinical applications. Attenuation correction is an essential requirement for quantification of PET data but MRI images do not directly provide a patient-specific attenuation map. Methods We further validate and extend a Computed Tomography (CT) and attenuation map (μ-map) synthesis method based on pre-acquired MRI-CT image pairs. The validation consists of comparing the CT images synthesised with the proposed method to the original CT images. PET images were acquired using two different tracers ({sup 18}F-FDG and {sup 18}F-florbetapir). They were then reconstructed and corrected for attenuation using the synthetic μ-maps and compared to the reference PET images corrected with the CT-based μ-maps. During the validation, we observed that the CT synthesis was inaccurate in areas such as the neck and the cerebellum, and propose a refinement to mitigate these problems, as well as an extension of the method to multi-contrast MRI data. Results With the improvements proposed, a significant enhancement in CT synthesis, which results in a reduced absolute error and a decrease in the bias when reconstructing PET images, was observed. For both tracers, on average, the absolute difference between the reference PET images and the PET images corrected with the proposed method was less than 2%, with a bias inferior to 1%. Conclusion With the proposed method, attenuation information can be accurately derived from MRI images by synthesising CT using routine anatomical sequences. MRI sequences, or combination of sequences, can be used to synthesise CT images, as long as they provide sufficient anatomical information. (orig.)

  12. Synthesis of isotopically modified ZnO nanoparticles and their potential as nanotoxicity tracers

    Energy Technology Data Exchange (ETDEWEB)

    Dybowska, Agnieszka D., E-mail: a.dybowska@nhm.ac.u [Department of Mineralogy, Natural History Museum London, Cromwell Road, London, SW7 5BD (United Kingdom); Croteau, Marie-Noele [U.S. Geological Survey, 345 Middlefield Road, MS 496, Menlo Park, CA 94025 (United States); Misra, Superb K.; Berhanu, Deborah [Department of Mineralogy, Natural History Museum London, Cromwell Road, London, SW7 5BD (United Kingdom); Luoma, Samuel N. [Department of Mineralogy, Natural History Museum London, Cromwell Road, London, SW7 5BD (United Kingdom); U.S. Geological Survey, 345 Middlefield Road, MS 496, Menlo Park, CA 94025 (United States); Christian, Paul; O' Brien, Paul [School of Chemistry, University of Manchester, M13 9PL, Manchester (United Kingdom); Valsami-Jones, Eugenia [Department of Mineralogy, Natural History Museum London, Cromwell Road, London, SW7 5BD (United Kingdom)

    2011-01-15

    Understanding the behavior of engineered nanoparticles in the environment and within organisms is perhaps the biggest obstacle to the safe development of nanotechnologies. Reliable tracing is a particular issue for nanoparticles such as ZnO, because Zn is an essential element and a common pollutant thus present at elevated background concentrations. We synthesized isotopically enriched (89.6%) with a rare isotope of Zn ({sup 67}Zn) ZnO nanoparticles and measured the uptake of {sup 67}Zn by L. stagnalis exposed to diatoms amended with the particles. Stable isotope technique is sufficiently sensitive to determine the uptake of Zn at an exposure equivalent to lower concentration range (<15 {mu}g g{sup -1}). Without a tracer, detection of newly accumulated Zn is significant at Zn exposure concentration only above 5000 {mu}g g{sup -1} which represents some of the most contaminated Zn conditions. Only by using a tracer we can study Zn uptake at a range of environmentally realistic exposure conditions. - ZnO nanoparticles with distinct isotopic composition can be tailor synthesized to be used as tracers of environmental fate and uptake by organisms.

  13. The single-biopsy approach in determining protein synthesis in human slow-turning-over tissue: use of flood-primed, continuous infusion of amino acid tracer

    DEFF Research Database (Denmark)

    Holm, Lars; Reitelseder, Søren; Dideriksen, Kasper

    2014-01-01

    Muscle protein synthesis (MPS) rate is determined conventionally by obtaining two or more tissue biopsies during a primed, continuous infusion of a stable isotopically labeled amino acid. The purpose of the present study was to test whether tracer priming given as a flooding dose, thereby securing...

  14. Synthesis of isotopically modified ZnO nanoparticles and their potential as nanotoxicity tracers

    Science.gov (United States)

    Dybowska, A.D.; Croteau, M.-N.; Misra, S.K.; Berhanu, D.; Luoma, S.N.; Christian, P.; O'Brien, P.; Valsami-Jones, E.

    2011-01-01

    Understanding the behavior of engineered nanoparticles in the environment and within organisms is perhaps the biggest obstacle to the safe development of nanotechnologies. Reliable tracing is a particular issue for nanoparticles such as ZnO, because Zn is an essential element and a common pollutant thus present at elevated background concentrations. We synthesized isotopically enriched (89.6%) with a rare isotope of Zn (67Zn) ZnO nanoparticles and measured the uptake of 67Zn by L. stagnalis exposed to diatoms amended with the particles. Stable isotope technique is sufficiently sensitive to determine the uptake of Zn at an exposure equivalent to lower concentration range (<15 ??g g-1). Without a tracer, detection of newly accumulated Zn is significant at Zn exposure concentration only above 5000 ??g g-1 which represents some of the most contaminated Zn conditions. Only by using a tracer we can study Zn uptake at a range of environmentally realistic exposure conditions. ?? 2010 Elsevier Ltd. All rights reserved.

  15. Fully automated [{sup 18}F]fluorocholine synthesis in the TracerLab MX{sub FDG} Coincidence synthesizer

    Energy Technology Data Exchange (ETDEWEB)

    Kryza, David [Laboratoire CREATIS-ANIMAGE, UMR 5515 Cnrs-U630 Inserm-Insa de Lyon (France); Hospices Civils de Lyon, Hopital E Herriot, Radiopharmacie, 69437 Lyon (France); Departement de Biophysique, Universite Lyon 1, domaine Rockfeller, 69008 Lyon (France)], E-mail: david.kryza@chu-lyon.fr; Tadino, Vincent [Optimized Radiochemical Applications, Saint-Nicolas (Belgium); Filannino, Maria Azzurra; Villeret, Guillaume; Lemoucheux, Laurent [Advanced Accelerator Applications, 01630 Saint Genis Pouilly (France)

    2008-02-15

    Introduction: We developed a new fully automated method for the radiosynthesis of [{sup 18}F]fluorocholine by modifying the commercial 2-[{sup 18}F]fluoro-2-D-deoxy-glucose ([{sup 18}F]FDG) synthesizer module (GE TracerLab MX, formerly Coincidence). Methods: [{sup 18}F]Flurocholine was synthesized by {sup 18}F-fluoroalkylation of N,N-dimethylaminoethanol using [{sup 18}F]fluorobromomethane as fluoromethylating agent. [{sup 18}F]Fluorobromomethane was produced by reaction of dibromomethane with [{sup 18}F]fluoride, assisted by Kryptofix 2.2.2. Results: After purification on solid-phase extraction cartridges, the [{sup 18}F]fluorocholine was obtained in 15-25% radiochemical yields (decay not corrected), with more than 99% radiochemical purity. Specific activity was more than 37 GBq/{mu}mol. Synthesis time was less than 35 min. Conclusion: This new automated synthesis technique provides high and reproducible yields that could be dedicated for routine use with the same [{sup 18}F]FDG disposable cassette system.

  16. Radionuclides as tracers of coastal processes in Brazil: review, synthesis, and perspectives

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Isaac R.; Burnett, William C., E-mail: santos@ocean.fsu.edu [Florida State University, Tallahassee, FL (United States). Dept. of Oceanography. Environmental Radioactivity Measurement Facility; Godoy, Jose M. [Instituto de Radioprotecao e Dosimetria (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil)

    2008-04-15

    We review the usefulness, limitations, significance, and coastal management implications of radionuclide measurements in Brazilian coastal environments. We focus on the use of radionuclides as tracers of sedimentary processes and submarine groundwater discharge (SGD). We also discuss artificial radionuclide contamination and high natural radioactivity areas. The interpretation of {sup 14}C-, {sup 137}Cs-, and {sup 210}Pb-derived sedimentation rates has provided evidence that inappropriate soil use by urban and agricultural activities has intensified erosion processes on land, which is reflected in depositional environments, such as coastal lagoons, estuaries and mangroves. Of the processes discussed in this paper, SGD is the one that requires the most scientific effort in the short-term. There have been only two case studies using {sup 222}Rn and radium isotopes as groundwater tracers in Brazil. These investigations showed that SGD can be a major source of nutrients and other dissolved species to the coastal ocean. Baseline {sup 137}Cs, {sup 90}Sr, {sup 239+240}Pu, and {sup 238}Pu concentrations in seawater from the whole Brazilian coastal zone are very low. Therefore, in spite of contamination problems in many ecosystems in the northern hemisphere, artificial radionuclide pollution appears to be negligible along the Brazilian coast. Phosphate fertilizer industries and petroleum processing facilities are the main economic activities producing Technologically Enhanced Naturally Occurring Radioactive Materials (TENORM). Even though a few attempts have been made to assess the radiological effects of these activities, their potential threats indicate a need for the radiological control of their wastes. This review showed that the number of studies within the field of environmental radioactivity is still small in Brazil and much more research is needed to understand processes of high interest for environmental managers. In the near future, it is likely that such studies

  17. {sup 11}C-harmine as a potential PET tracer for ductal pancreas cancer: in vitro studies

    Energy Technology Data Exchange (ETDEWEB)

    Herlin, G.; Persson, B.; Laangstroem, B.; Aspelin, P. [Department of Diagnostic Radiology, Huddinge University Hospital, 141-86 Stockholm (Sweden); Bergstroem, M. [Uppsala University PET Centre, Uppsala (Sweden)

    2003-04-01

    Our objective was to find a tracer in diagnosing human pancreatic cancer using positron emission tomography (PET). For this purpose in vitro test of pancreatic tissues with autoradiography was used. Autoradiography was performed with {sup 11}C-harmine (a MAO-A-inhibitor) with and without competitive inhibition. Tissue preparations were obtained from normal human pancreas and pancreatic cancer. The uptake was compared with rat brain or pig brain, tissues with high expression of MAO-A. Nine autoradiography studies on 16 samples from five different human pancreatic cancers gave a significant level of specific binding of {sup 11}C-harmine in 13, and 3 samples did not give a significant level of specific binding of {sup 11}C-harmine. All 16 samples were analysed with autoradiography. Compared with rat brain, the uptake in the human cancers varied between 9 and 43% except for one tissue preparation which had a too low value for measurement. This study shows expression of MAO-A in human pancreatic cancer. This is readily characterised in vitro. The potential use of {sup 11}C-harmine in the diagnosis of pancreatic cancer using PET might be limited, but further PET studies are necessary. (orig.)

  18. Planetary Nebulae as Tracers of the Intergalactic Stellar Background: a Population Synthesis Theoretical Approach

    CERN Document Server

    Buzzoni, A

    2004-01-01

    We wish to assess the relationship between the population of planetary nebulae (PNe) and a given parent stellar population from a theoretical point of view. Our results rely on original population synthesis models used to estimate the expected luminosity-specific PN density accounting for different evolutionary scenarios and star formation histories, as observed in galaxies in the near Universe. For a complete PN sample, we find that 1 PN/1.5E06 L(sun) a safe (IMF-independent) lower limit to the traced global bolometric luminosity of the parent stellar population. A tentative application to Virgo cluster data allows us to place a lower limit at ~7% for the global B luminosity of the cluster provided by "loose" intergalactic stars.

  19. Radionuclides as tracers of coastal processes in Brazil: review, synthesis, and perspectives

    Directory of Open Access Journals (Sweden)

    Isaac R. Santos

    2008-06-01

    Full Text Available We review the usefulness, limitations, significance, and coastal management implications of radionuclide measurements in Brazilian coastal environments. We focus on the use of radionuclides as tracers of sedimentary processes and submarine groundwater discharge (SGD. We also discuss artificial radionuclide contamination and high natural radioactivity areas. The interpretation of 14C-, 137Cs-, and 210Pb-derived sedimentation rates has provided evidence that inappropriate soil use by urban and agricultural activities has intensified erosion processes on land, which is reflected in depositional environments, such as coastal lagoons, estuaries and mangroves. Of the processes discussed in this paper, SGD is the one that requires the most scientific effort in the short-term. There have been only two case studies using 222Rn and radium isotopes as groundwater tracers in Brazil. These investigations showed that SGD can be a major source of nutrients and other dissolved species to the coastal ocean. Baseline 137Cs, 90Sr, 239+240Pu, and 238Pu concentrations in seawater from the whole Brazilian coastal zone are very low. Therefore, in spite of contamination problems in many ecosystems in the northern hemisphere, artificial radionuclide pollution appears to be negligible along the Brazilian coast. Phosphate fertilizer industries and petroleum processing facilities are the main economic activities producing Technologically Enhanced Naturally Occurring Radioactive Materials (TENORM. Even though a few attempts have been made to assess the radiological effects of these activities, their potential threats indicate a need for the radiological control of their wastes. This review showed that the number of studies within the field of environmental radioactivity is still small in Brazil and much more research is needed to understand processes of high interest for environmental managers. In the near future, it is likely that such studies in Brazil will move from

  20. Evaluation of 4-[18F]fluorobenzoyl-FALGEA-NH2 as a positron emission tomography tracer for epidermal growth factor receptor mutation variant III imaging in cancer

    DEFF Research Database (Denmark)

    Denholt, Charlotte Lund; Binderup, Tina; Stockhausen, Marie-Thérése;

    2011-01-01

    This study describes the radiosynthesis, in vitro and in vivo evaluation of the novel small peptide radioligand, 4-[(18)F]fluorobenzoyl-Phe-Ala-Leu-Gly-Glu-Ala-NH(2,) ([(18)F]FBA-FALGEA-NH(2)) as a positron emission tomography (PET) tracer for imaging of the cancer specific epidermal growth factor...

  1. Synthesis and PET imaging of the benzodiazepine receptor tracer [N-methyl-{sup 11}C]iomazenil

    Energy Technology Data Exchange (ETDEWEB)

    Baldwin, Ronald M.; Horti, Andrew G.; Bremner, J. Douglas; Stratton, Morgan D.; Dannals, Robert F.; Ravert, Hayden T.; Zea-Ponce, Yolanda; Ng, Chin K.; Dey, Holley M.; Soufer, Robert; Charney, Dennis S.; Mazza, Samuel M.; Sparks, Richard B.; Stubbs, James B.; Innis, Robert B

    1995-07-01

    The central benzodiazepine receptor tracer [N-methyl-{sup 11}C]iomazenil (Ro 16-0154) was synthesized by alkylation of the desmethyl precursor noriomazenil with [{sup 11}C]methyl iodide. The [{sup 11}C]CH{sub 3}I (prepared by reduction of [{sup 11}C]CO{sub 2} with LiAlH{sub 4} followed by reaction with HI) was reacted with noriomazenil inN,N -dimethylformamide and Bu{sub 4}N{sup +}OH{sup -} for 1 min at 80 deg. C and purified by HPLC (C{sub 18}, 34% CH{sub 3}CN/H{sub 2}O, 7 mL/min). The product was obtained with synthesis time 35 {+-} 5 min (mean {+-} SD, n = 7), radiochemical yield (EOB) 36 {+-} 16%, radiochemical purity 99 {+-} 1%, and specific activity 5100 {+-} 2800 mCi/{mu}mol. Absorbed radiation doses were calculated from previously acquired human biodistribution data. The urinary bladder wall received the highest dose (0.099 mGy/MBq) for 4.8 h voiding interval and the effective dose equivalent was 0.015 mSv/MBq. After i.v. injection of [{sup 11}C]iomazenil in an adult baboon or healthy human volunteer, radioactivity accumulated in the cortex with time-activity curves in agreement with results obtained with [{sup 11}C]flumazenil PET and [{sup 123}I]iomazenil SPECT studies. The count rate was sufficient to obtain quantitative images up to 2 h post-injection with a 14 mCi injection. These results suggest that [{sup 11}C]iomazenil will be a useful agent for measuring benzodiazepine receptorsin vivo by positron emission tomography.

  2. Novel tracers and their development for the imaging of metastatic prostate cancer.

    Science.gov (United States)

    Apolo, Andrea B; Pandit-Taskar, Neeta; Morris, Michael J

    2008-12-01

    There are presently no accurate methods of imaging prostate cancer metastases to bone. An unprecedented number of novel imaging agents, based on the biology of the disease, are now available for testing. We reviewed contemporary molecular imaging modalities that have been tested in humans with metastatic prostate cancer, with consideration of the studies' adherence to current prostate cancer clinical trial designs. Articles from the years 2002 to 2008 on PET using (18)F-FDG, (11)C-choline, (18)F-choline, (18)F-flouride, (11)C-acetate, (11)C-methionine, and (18)F-fluoro-5alpha-dihydrotestosterone in patients with metastatic prostate cancer were reviewed. Although these studies are encouraging, most focus on the rising population with prostate-specific antigen, and many involve small numbers of patients and do not adhere to consensus criteria for clinical trial designs in prostate cancer. Hence, although many promising agents are available for testing, such studies would benefit from closer collaboration between those in the fields of medical oncology and nuclear medicine.

  3. Environmental Tracers

    Directory of Open Access Journals (Sweden)

    Trevor Elliot

    2014-10-01

    Full Text Available Environmental tracers continue to provide an important tool for understanding the source, flow and mixing dynamics of water resource systems through their imprint on the system or their sensitivity to alteration within it. However, 60 years or so after the first isotopic tracer studies were applied to hydrology, the use of isotopes and other environmental tracers are still not routinely necessarily applied in hydrogeological and water resources investigations where appropriate. There is therefore a continuing need to promote their use for developing sustainable management policies for the protection of water resources and the aquatic environment. This Special Issue focuses on the robustness or fitness-for-purpose of the application and use of environmental tracers in addressing problems and opportunities scientifically, to promote their wider use and to address substantive issues of vulnerability, sustainability, and uncertainty in (groundwater resources systems and their management.

  4. Synthesis and preclinical evaluation of [{sup 11}C]PAQ as a PET imaging tracer for VEGFR-2

    Energy Technology Data Exchange (ETDEWEB)

    Samen, Erik; Stone-Elander, Sharon [Karolinska University Hospital Solna, Karolinska Pharmacy, Stockholm (Sweden); Karolinska Institutet, Clinical Neurosciences, Stockholm (Sweden); Thorell, Jan-Olov [Karolinska University Hospital Solna, Karolinska Pharmacy, Stockholm (Sweden); Lu, Li [Karolinska Institutet, Clinical Neurosciences, Stockholm (Sweden); Tegnebratt, Tetyana; Holmgren, Lars [Karolinska Institutet, Cancer Center Karolinska, Oncology-Pathology, Stockholm (Sweden)

    2009-08-15

    (R,S)-N-(4-Bromo-2-fluorophenyl)-6-methoxy-7-((1-methyl-3-piperidinyl)methoxy)-4-quinazolinamine (PAQ) is a tyrosine kinase inhibitor with high affinity for the vascular endothelial growth factor receptor 2 (VEGFR-2), which plays an important role in tumour angiogenesis. The aim of this work was to develop and evaluate in mice the {sup 11}C-labelled analogue as an in vivo tracer for VEGFR-2 expression in solid tumours. [{sup 11}C]PAQ was synthesized by an N-methylation of desmethyl-PAQ using [{sup 11}C]methyl iodide. The tracer's pharmacokinetic properties and its distribution in both subcutaneous and intraperitoneal tumour models were evaluated with positron emission tomography (PET). [{sup 18}F]FDG was used as a reference tracer for tumour growth. PET results were corroborated by ex vivo and in vitro phosphor imaging and immunohistochemical analyses. In vitro assays and PET in healthy animals revealed low tracer metabolism, limited excretion over 60 min and a saturable and irreversible binding. Radiotracer uptake in subcutaneous tumour masses was low, while focal areas of high uptake (up to 8% ID/g) were observed in regions connecting the tumour to the host. Uptake was similarly high but more distributed in tumours growing within the peritoneum. The pattern of radiotracer uptake was generally different from that of the metabolic tracer [{sup 18}F]FDG and correlated well with variations in VEGFR-2 expression determined ex vivo by immunohistochemical analysis. These results suggest that [{sup 11}C]PAQ has potential as a noninvasive PET tracer for in vivo imaging of VEGFR-2 expression in angiogenic ''hot spots''. (orig.)

  5. Combined Methylene Blue Dye andRadioactive Tracer Technique for Sentinel Lymph Node Localization in Early Breast Cancer

    Directory of Open Access Journals (Sweden)

    Abdolrasoul Talei

    2010-10-01

    Full Text Available Background: Sentinel lymph node biopsy is a technique used to identify the axillary node most likely to contain tumor cells that have metastasized from a primarycarcinoma of the breast. This technique provides accurate staging with fewer complications than axillary dissection and may result in decreased costs. We designed the present study to determine the accuracy and success rate of a combined blue dyeand radioactive tracer technique in sentinel node localization. Methods: This prospective study included 70 patients with early stage (tumor>5cm; T1, T2 operable breast cancer and nonpalpable axillary lymphadenopathy seen between 2005 and 2009. Patients underwent sentinel lymph node localization using 4mL of blue dye combined with radioactive colloid. After identification and removal of the sentinel node(s, the axilla was checked for any residual radioactivity. A sentinelnode was defined as any node that was hot, hot and blue or only blue.Results:The sentinel node was identified in 66 patients with a detection rate of 94.2%,and a mean of 1.5 sentinel nodes were identified and harvested (range of 1-4. In 23cases, the sentinel lymph node contained metastatic disease on pathological assessment.There was no pathological evidence of any metastases in the sentinel node in the remaining 43 patients. All sentinel lymph nodes were located in level I of the axillary region. In four patients, no sentinel lymph node was found, so axillary dissection was performed. The sensitivity of the procedure in predicting further axillary disease was 95.6% with a specificity of 97.6%.Conclusion: The present study describes the blue dye and radioisotope localization technique as successful in identifying the sentinel lymph node in early-stage breast cancer patients.

  6. Synthesis of a novel polyamidoamine dendrimer conjugating with alkali blue as a lymphatic tracer and study on the lymphatic targeting in vivo.

    Science.gov (United States)

    Yang, Rui; Xia, Suxia; Ye, Tiantian; Yao, Jianhua; Zhang, Ruizhi; Wang, Shujun; Wang, Siling

    2016-09-01

    In this study, a novel lymphatic tracer polyamidoamin-alkali blue (PAMAM-AB) was synthesized in order to evaluate the intra-lymphatic targeting ability and lymphatic tropism of PAMAM-AB after subcutaneous administration. UV-Vis, FT-IR, NMR and HPLC characterization were performed to prove the successful synthesis of PAMAM-AB. The calculated AB payload of PAMAM-AB conjugate was seven per dendrimer molecule (27.16% by weight). Hydrolysis stability of PAMAM-AB in vitro was evaluated, which was stable in PBS and human plasma. Lymphatic tracing were studied to determine the blue-stained intensity of PAMAM-AB in right popliteral lymph nodes (PLNs), iliac lymph nodes (ILNs) and para-aortic lymph nodes (PALNs) after subcutaneous administration. The pharmacokinetics and biodistribution of PAMAM-AB in mice were investigated. PLNs, ILNs and PALNs could be obviously blue-stained within 10 min after PAMAM-AB administration, and displayed a more rapid lymphatic absorption, a higher AUC value in lymph nodes and a longer lymph nodes residence time compared with methylene blue solution (MB-S), MB water-in-oil microemulsion (MB-ME), MB multiple microemulsion (MB-MME). Enhanced lymphatic drainage from the injection site and uptake into lymph of PAMAM-AB indicated that PAMAM-AB possesses the double function of lymphatic tracing and lymphatic targeting, and suggested the potential for the development of lymphatic targeting vectors or as a lymphatic tracer in its own right.

  7. A validation of the application of D(2)O stable isotope tracer techniques for monitoring day-to-day changes in muscle protein subfraction synthesis in humans.

    Science.gov (United States)

    Wilkinson, Daniel J; Franchi, Martino V; Brook, Matthew S; Narici, Marco V; Williams, John P; Mitchell, William K; Szewczyk, Nathaniel J; Greenhaff, Paul L; Atherton, Philip J; Smith, Kenneth

    2014-03-01

    Quantification of muscle protein synthesis (MPS) remains a cornerstone for understanding the control of muscle mass. Traditional [(13)C]amino acid tracer methodologies necessitate sustained bed rest and intravenous cannulation(s), restricting studies to ~12 h, and thus cannot holistically inform on diurnal MPS. This limits insight into the regulation of habitual muscle metabolism in health, aging, and disease while querying the utility of tracer techniques to predict the long-term efficacy of anabolic/anticatabolic interventions. We tested the efficacy of the D2O tracer for quantifying MPS over a period not feasible with (13)C tracers and too short to quantify changes in mass. Eight men (22 ± 3.5 yr) undertook one-legged resistance exercise over an 8-day period (4 × 8-10 repetitions, 80% 1RM every 2nd day, to yield "nonexercised" vs. "exercise" leg comparisons), with vastus lateralis biopsies taken bilaterally at 0, 2, 4, and 8 days. After day 0 biopsies, participants consumed a D2O bolus (150 ml, 70 atom%); saliva was collected daily. Fractional synthetic rates (FSRs) of myofibrillar (MyoPS), sarcoplasmic (SPS), and collagen (CPS) protein fractions were measured by GC-pyrolysis-IRMS and TC/EA-IRMS. Body water initially enriched at 0.16-0.24 APE decayed at ~0.009%/day. In the nonexercised leg, MyoPS was 1.45 ± 0.10, 1.47 ± 0.06, and 1.35 ± 0.07%/day at 0-2, 0-4, and 0-8 days, respectively (~0.05-0.06%/h). MyoPS was greater in the exercised leg (0-2 days: 1.97 ± 0.13%/day; 0-4 days: 1.96 ± 0.15%/day, P < 0.01; 0-8 days: 1.79 ± 0.12%/day, P < 0.05). CPS was slower than MyoPS but followed a similar pattern, with the exercised leg tending to yield greater FSRs (0-2 days: 1.14 ± 0.13 vs. 1.45 ± 0.15%/day; 0-4 days: 1.13 ± 0.07%/day vs. 1.47 ± 0.18%/day; 0-8 days: 1.03 ± 0.09%/day vs. 1.40 ± 0.11%/day). SPS remained unchanged. Therefore, D2O has unrivaled utility to quantify day-to-day MPS in humans and inform on short-term changes in anabolism and

  8. Synthesis and evaluation of [(18)F]-fluoromethyl triphenylphosphonium cation as a novel mitochondria-specific positron emission tomography tracer.

    Science.gov (United States)

    Zeng, Huahui; Wu, Xiangxiang; Song, Fahuan; Xu, Caiyun; Liu, Hao; Liu, Wendi

    2016-08-08

    We developed a radiosynthesis of the voltage sensitive tracer [(18)F]-fluoromethyltriphenylphosphonium cation ([(18)F]-FTPMP), giving high yield (30-34%, decay-corrected), radiochemical purity (>99%) and specific activity (about 760 GBq/μmol). [(18)F]-FTPMP had suitable lipophilicity (logP = 0.91 ± 0.03) and high in vivo/vitro stability. Biodistribution studies showed that [(18)F]-FTPMP had high heart uptake (>7%ID/g from 10 min to 120 min postinjection) and rapid clearance from the background. Clear cardiac images were obtained at different time periods, and the infarction areas could be detected sensitively with small-animal PET. The autoradiography and myocardial membrane potential studies confirmed the mitochondria specific of [(18)F]-FTPMP in rat myocardia. These excellent pharmacokinetic properties suggest [(18)F]-FTPMP is a promising mitochondria-specific tracer for clinical PET imaging of myocardial diseases associated with mitochondrial dysfunction.

  9. Insights on the mechanism for synthesis of methylenedianiline from aniline and formaldehyde through HPLC-MS and isotope tracer studies

    Institute of Scientific and Technical Information of China (English)

    Chen Ye Wang; Hui Quan Li; Li Guo Wang; Yan Cao; Hai Tao Liu; Yi Zhang

    2012-01-01

    The mechanism for synthesis of 4,4-methylenedianiline (MDA) via condensation reaction of aniline with formaldehyde has been studied extensively in this paper.The intermediate and by-products were isolated and identified.The combination of isotope labeling and HPLC-MS characterizations disclosed that the reaction proceeded through an SN2 reaction mechanism.Moreover,the effect of aniline/formaldehyde molar ratio on the formation of MDA was investigated.This work would be of significance to understand the reaction mechanism deeply and provide valuable information for further improving the yield of desired product.

  10. Synthesis of sup 11 C-labeled imipramine and its biodistribution in mice; A potential tracer for positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Nakamura, Hitoshi; Edo, Kiyoto; Hishinuma, Takanori; Mizugaki, Michinao (Tohoku University Hospital, Sendai (Japan). Department of Pharmaceutical Sciences); Takahashi, Toshihiro; Ido, Tatsuo

    1989-12-01

    A tricyclic antidepressant, {sup 11}C-labeled imipramine was synthesized by N-methylation of desipramine with {sup 11}CH{sub 3}I to assist in the imaging of the human imipramine receptor by positron emission tomography. The radiochemical yield after purification of {sup 11}C-imipramine by high performance liquid chromatography was 28-63% at a specific activity of 26-53 Ci/mmol. The time required for synthesis, including purification was 30 min from the end of {sup 11}CH{sub 3}I trapping. The organ distribution of {sup 11}C-imipramine was investigated in mice at various times after i.v. injection. The main accumulation of radioactivity was in the kidney, followed by the lung and the heart. In the brain, the radioactivity levels in the hypothalamus and striatum were the highest and remained constant, differentiating them from other portions of the brain. Furthermore, the result of a binding assay with {sup 3}H-labeled imipramine suggested that the regional distribution of {sup 11}C-imipramine in the same mouse brain correlated to that of the high affinity imipramine binding site. (author).

  11. Can positron emission tomography/computed tomography with the dual tracers fluorine-18 fluoroestradiol and fluorodeoxyglucose predict neoadjuvant chemotherapy response of breast cancer?--A pilot study.

    Directory of Open Access Journals (Sweden)

    Zhongyi Yang

    Full Text Available OBJECTIVE: To assess the clinical value of dual tracers Positron emission tomography/computed tomography (PET/CT (18F-fluoroestradiol ((18F-FES and (18F-fluorodeoxyglucose ((18F-FDG in predicting neoadjuvant chemotherapy response (NAC of breast cancer. METHODS: Eighteen consecutive patients with newly diagnosed, non-inflammatory, stage II and III breast cancer undergoing NAC were included. Before chemotherapy, they underwent both (18F-FES and (18F-FDG PET/CT scans. Surgery was performed after three to six cycles of chemotherapy. Tumor response was graded and divided into two groups: the responders and non-responders. We used the maximum standardized uptake value (SUVmax to qualify each primary lesion. RESULTS: Pathologic analysis revealed 10 patients were responders while the other 8 patients were non-responders. There was no statistical difference of SUVmax-FDG and tumor size between these two groups (P>0.05. On the contrary, SUVmax-FES was lower in responders (1.75±0.66 versus 4.42±1.14; U=5, P=0.002; and SUVmax-FES/FDG also showed great value in predicting outcome (0.16±0.06 versus 0.54±0.22; U=5, P=0.002. CONCLUSIONS: Our study showed (18F-FES PET/CT might be feasible to predict response of NAC. However, whether the use of dual tracers (18F-FES and (18F-FDG has complementary value should be further studied.

  12. Detection of prostatic cancer by solid-phase radioimmunoassay of serum prostatic acid phosphatase. [/sup 125/I tracer technique

    Energy Technology Data Exchange (ETDEWEB)

    Foti, A.; Cooper, J.F.; Herschman, H.; Malvaez, R.R.

    1977-12-22

    We compared our radioimmunoassay with the standard enzyme assay for prostatic acid phosphatase in the diagnosis of prostatic cancer. Serum samples from 50 controls, 113 patients with prostatic cancer, 36 with benign prostatic hyperplasia, 83 with other cancers, 20 with gastrointestinal disorders and 28 with total prostatectomies were randomized and studied by radioimmunoassay and enzyme assay. When the upper limit was set at 8.0 ng per milliliter (mean + 4 S.D.) the radioimmunoassay diagnosed prostatic cancer in 33, 79, 71 and 92 percent of the patients with Stage I, II, III and IV disease. In contrast, the enzyme assay detected elevations of enzyme in the serum of 12, 15, 29, and 60 percent respectively. No false-positive results were detected by either assay in normal controls but the radioimmunoassay test was positive in two patients with benign prostatic hyperplasia, in one patient after total prostatectomy, in nine with other cancers and in one of the group with gastrointestinal disorders. In contrast to the enzyme assay, the radioimmunoassay distinguished over half the cases of intracapsular prostatic cancer.

  13. 亚甲蓝示踪乳腺癌效果的研究%The Study of Effects on Methylene Blue as Breast Cancer Tracer

    Institute of Scientific and Technical Information of China (English)

    周国庆; 郑冬梅; 崔保国; 张曼丽; 兰涛

    2013-01-01

      目的:亚甲蓝示踪乳腺癌效果的评价.方法:将术前确诊乳腺癌的患者进行乳腺癌组织及其周围注射亚甲蓝,术中进行腋窝淋巴结清扫时,将染色与非染色淋巴结进行分类,并标明各淋巴结的所在组别.结合病理区分淋巴结转移的真阴性、假阴性、真阳性、假阳性.以此作为乳腺癌示踪技术的成功与否的依据.结果:63例检出的前哨淋巴结中,阴性26例,阳性37例,阳性率58.73%.65例腋窝淋巴结阳性38例,阳性率58.46%.SLN与ALN经病理检查完全符合者36例.2例前哨淋巴结阴性而腋窝淋巴结阳性,1例前哨淋巴结阳性而腋窝淋巴结阴性.前哨淋巴结活检技术的评价:灵敏度(SLN阳性数37/腋窝淋巴结转移数38)97.3%,准确度(SLN真阳性与真阴性的数之和60/S L N活检总数63)为95.2%,假阳性率(SLN假阳性的例数1/腋窝淋巴结转移例数38)2.6%,假阴性率(SLN假阴性的例数2/腋窝淋巴结转移例数38)5.2%.结论:使用染料亚甲蓝示踪乳腺癌前哨淋巴结活检,准确掌握适应症、示踪条件后,检出的淋巴结敏感性和准确性均较高,临床应用简便,安全性高,能较准确地预测腋窝淋巴结转移的情况.%Objective:The study of the effects of methylene blue tracer breast cancer.Methods:The preoperative diagnosis of breast cancer patients with breast cancer tissue and its surrounding injection of methylene blue, surgery for axillary lymph node dissection, staining and non-staining lymph node classification, and indicate where each lymph node group. Combined with pathological distinction between lymph node metastasis of true negative, false negative, true positive, false positive. As a basis for breast cancer tracer technique the success.Results:63 cases detected in the sentinel lymph node negative in 26 cases, 37 cases positive, the positive rate of 58.73%. 65 cases of axillary lymph node was positive in 38 cases, the positive rate of 58.46%. SLN and ALN

  14. Novel Preclinical and Radiopharmaceutical Aspects of [68Ga]Ga-PSMA-HBED-CC: A New PET Tracer for Imaging of Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Matthias Eder

    2014-06-01

    Full Text Available The detection of prostate cancer lesions by PET imaging of the prostate-specific membrane antigen (PSMA has gained highest clinical impact during the last years. 68Ga-labelled Glu-urea-Lys(Ahx-HBED-CC ([68Ga]Ga-PSMA-HBED-CC represents a successful novel PSMA inhibitor radiotracer which has recently demonstrated its suitability in individual first-in-man studies. The radiometal chelator HBED-CC used in this molecule represents a rather rarely used acyclic complexing agent with chemical characteristics favourably influencing the biological functionality of the PSMA inhibitor. The simple replacement of HBED-CC by the prominent radiometal chelator DOTA was shown to dramatically reduce the in vivo imaging quality of the respective 68Ga-labelled PSMA-targeted tracer proving that HBED-CC contributes intrinsically to the PSMA binding of the Glu-urea-Lys(Ahx pharmacophore. Owing to the obvious growing clinical impact, this work aims to reflect the properties of HBED-CC as acyclic radiometal chelator and presents novel preclinical data and relevant aspects of the radiopharmaceutical production process of [68Ga]Ga-PSMA-HBED-CC.

  15. How should tracers be injected to detect for sentinel nodes in gastric cancer – submucosally from inside or subserosally from outside of the stomach?

    Directory of Open Access Journals (Sweden)

    Yoshida Kazumichi

    2008-12-01

    Full Text Available Abstract Background In sentinel node (SN detection for cases of early gastric cancer, the submucosal dye injection method appears to be more reasonable than the subserosal injection. To compare the two injection methods, we have focused on the rate of concordance between hot nodes (HNs obtained from the radioisotope (RI method and green nodes (GNs obtained from the dye-guided method in addition to the number and distribution of GNs detected, and the sensitivity of metastatic detection. Methods The subjects of this study were 63 consecutive patients with gastric cancer (sT1–T2, sN0, tumor diameter ≦ 4 cm in whom we attempted SN detection using a combination of RI and dye methods. 99mTc-tin colloid was injected a day before the surgery, and indocyanine green was injected either submucosally (n = 43 with endoscopes or subserosally (n = 20 by direct vision. Results An average of hot and green nodes (H&G: 4 ± 3 vs. 4 ± 3, hot and non-green nodes (H&NG: 2 ± 3 vs. 1 ± 2, cold and green nodes (C&G: 2 ± 2 vs. 3 ± 4, and the rate of concordance (H&G/H&G + H&NG + C&G: 45 + 27% vs. 48 ± 30% were not significantly different between the submucosal and subserosal injection methods. The spread of GNs to tier 2 stations (24% vs. 30% and metastatic detection sensitivity (86% vs. 100% were also not different between the submucosal and subserosal injection methods. Conclusion The tracer injection sites do not have to be limited to the submucosa.

  16. Tracer design for magnetic particle imaging (invited).

    Science.gov (United States)

    Ferguson, R Matthew; Khandhar, Amit P; Krishnan, Kannan M

    2012-04-01

    Magnetic particle imaging (MPI) uses safe iron oxide nanoparticle tracers to offer fundamentally new capabilities for medical imaging, in applications as vascular imaging and ultra-sensitive cancer therapeutics. MPI is perhaps the first medical imaging platform to intrinsically exploit nanoscale material properties. MPI tracers contain magnetic nanoparticles whose tunable, size-dependent magnetic properties can be optimized by selecting a particular particle size and narrow size-distribution. In this paper we present experimental MPI measurements acquired using a homemade MPI magnetometer: a zero-dimensional MPI imaging system designed to characterize tracer performance by measuring the derivative of the time-varying tracer magnetization, M'(H(t)), at a driving frequency of 25 kHz. We show that MPI performance is optimized by selecting phase-pure magnetite tracers of a particular size and narrow size distribution; in this work, tracers with 20 nm median diameter, log-normal distribution shape parameter, σ(v), equal to 0.26, and hydrodynamic diameter equal to 30 nm showed the best performance. Furthermore, these optimized MPI tracers show 4 × greater signal intensity (measured at the third harmonic) and 20% better spatial resolution compared with commercial nanoparticles developed for MRI.

  17. Packet Tracer network simulator

    CERN Document Server

    Jesin, A

    2014-01-01

    A practical, fast-paced guide that gives you all the information you need to successfully create networks and simulate them using Packet Tracer.Packet Tracer Network Simulator is aimed at students, instructors, and network administrators who wish to use this simulator to learn how to perform networking instead of investing in expensive, specialized hardware. This book assumes that you have a good amount of Cisco networking knowledge, and it will focus more on Packet Tracer rather than networking.

  18. Acetate/acetyl-CoA metabolism associated with cancer fatty acid synthesis: overview and application.

    Science.gov (United States)

    Yoshii, Yukie; Furukawa, Takako; Saga, Tsuneo; Fujibayashi, Yasuhisa

    2015-01-28

    Understanding cancer-specific metabolism is important for identifying novel targets for cancer diagnosis and therapy. Induced acetate/acetyl CoA metabolism is a notable feature that is related to fatty acid synthesis supporting tumor growth. In this review, we focused on the recent findings related to cancer acetate/acetyl CoA metabolism. We also introduce [1-¹¹C]acetate positron emission tomography (PET), which is a useful tool to visualize up-regulation of acetate/acetyl CoA metabolism in cancer, and discuss the utility of [1-¹¹C]acetate PET in cancer diagnosis and its application to personalized medicine.

  19. Synthesis and evaluation of cholecystokinin trimers: a multivalent approach to pancreatic cancer detection and treatment.

    Science.gov (United States)

    Brabez, Nabila; Nguyen, Kevin L; Saunders, Kara; Lacy, Ryan; Xu, Liping; Gillies, Robert J; Lynch, Ronald M; Chassaing, Gerard; Lavielle, Solange; Hruby, Victor J

    2013-04-15

    In the quest for novel tools for early detection and treatment of cancer, we propose the use of multimers targeting overexpressed receptors at the cancer cell surface. Indeed, multimers are prone to create multivalent interactions, more potent and specific than their corresponding monovalent versions, thus enabling the potential for early detection. There is a lack of tools for early detection of pancreatic cancer, one of the deadliest forms of cancer, but CCK2-R overexpression on pancreatic cancer cells makes CCK based multimers potential markers for these cells. In this Letter, we describe the synthesis and evaluation of CCK trimers targeting overexpressed CCK2-R.

  20. Tracer attenuation in groundwater

    Science.gov (United States)

    Cvetkovic, Vladimir

    2011-12-01

    The self-purifying capacity of aquifers strongly depends on the attenuation of waterborne contaminants, i.e., irreversible loss of contaminant mass on a given scale as a result of coupled transport and transformation processes. A general formulation of tracer attenuation in groundwater is presented. Basic sensitivities of attenuation to macrodispersion and retention are illustrated for a few typical retention mechanisms. Tracer recovery is suggested as an experimental proxy for attenuation. Unique experimental data of tracer recovery in crystalline rock compare favorably with the theoretical model that is based on diffusion-controlled retention. Non-Fickian hydrodynamic transport has potentially a large impact on field-scale attenuation of dissolved contaminants.

  1. Final Progress Report for Project Entitled: Quantum Dot Tracers for Use in Engineered Geothermal Systems

    Energy Technology Data Exchange (ETDEWEB)

    Rose, Peter [Univ. of Utah, Salt Lake City, UT (United States); Bartl, Michael [Univ. of Utah, Salt Lake City, UT (United States); Reimus, Paul [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Williams, Mark [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Mella, Mike [Univ. of Utah, Salt Lake City, UT (United States)

    2015-09-12

    The objective of this project was to develop and demonstrate a new class of tracers that offer great promise for use in characterizing fracture networks in EGS reservoirs. From laboratory synthesis and testing through numerical modeling and field demonstrations, we have demonstrated the amazing versatility and applicability of quantum dot tracers. This report summarizes the results of four years of research into the design, synthesis, and characterization of semiconductor nanocrystals (quantum dots) for use as geothermal tracers.

  2. Single valproic acid treatment inhibits glycogen and RNA ribose turnover while disrupting glucose-derived cholesterol synthesis in liver as revealed by the [U-C(6)]-d-glucose tracer in mice.

    Science.gov (United States)

    Beger, Richard D; Hansen, Deborah K; Schnackenberg, Laura K; Cross, Brandie M; Fatollahi, Javad J; Lagunero, F Tracy; Sarnyai, Zoltan; Boros, Laszlo G

    2009-09-01

    Previous genetic and proteomic studies identified altered activity of various enzymes such as those of fatty acid metabolism and glycogen synthesis after a single toxic dose of valproic acid (VPA) in rats. In this study, we demonstrate the effect of VPA on metabolite synthesis flux rates and the possible use of abnormal (13)C labeled glucose-derived metabolites in plasma or urine as early markers of toxicity. Female CD-1 mice were injected subcutaneously with saline or 600 mg/kg) VPA. Twelve hours later, the mice were injected with an intraperitoneal load of 1 g/kg [U-(13)C]-d-glucose. (13)C isotopomers of glycogen glucose and RNA ribose in liver, kidney and brain tissue, as well as glucose disposal via cholesterol and glucose in the plasma and urine were determined. The levels of all of the positional (13)C isotopomers of glucose were similar in plasma, suggesting that a single VPA dose does not disturb glucose absorption, uptake or hepatic glucose metabolism. Three-hour urine samples showed an increase in the injected tracer indicating a decreased glucose re-absorption via kidney tubules. (13)C labeled glucose deposited as liver glycogen or as ribose of RNA were decreased by VPA treatment; incorporation of (13)C via acetyl-CoA into plasma cholesterol was significantly lower at 60 min. The severe decreases in glucose-derived carbon flux into plasma and kidney-bound cholesterol, liver glycogen and RNA ribose synthesis, as well as decreased glucose re-absorption and an increased disposal via urine all serve as early flux markers of VPA-induced adverse metabolic effects in the host.

  3. Synthesis and evaluation of 6-[{sup 18}F]fluoro-3-(2(S)-azetidinylmethoxy)pyridine as a PET tracer for nicotinic acetylcholine receptors

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Y.-S. E-mail: ding@bnl.gov; Liu, N.; Wang, T.; Marecek, J.; Garza, V.; Ojima, I.; Fowler, J.S

    2000-05-01

    Both ABT-594 ((R)-2-chloro-5-(2-azetidinylmethoxy)pyridine) and A-85380 (3-[2(S)-2-azetidinylmethoxy]pyridine), novel nicotinic agonists that possess potent non-opioid analgesic properties, have high affinity for neuronal nicotinic acetylcholine receptors (nAChR) but do not elicit the pronounced toxicity of epibatidine. 6-[{sup 18}F]Fluoro-3-(2(S)-azetidinylmethoxy)pyridine (6-[{sup 18}F]fluoro-A-85380), a F-18 labeled analogue of these two compounds, is therefore a promising radioligand for positron emission tomography (PET) studies in humans. The use of trimethylammonium as a leaving group in nucleophilic aromatic substitution reactions has proven to be a versatile and efficient strategy, and offers several advantages over other leaving groups. Here, we report the synthetic strategy for the preparation of a precursor, as a trimethylammonium iodide salt, and its use in the radiosynthesis to 6-[{sup 18}F]fluoro-A-85380. Preliminary comparative PET studies of 6-[{sup 18}F]fluoro-A-85380 and 2-[{sup 18}F]fluoro-A-85380 were carried out in baboon to examine their suitability as tracers for studying nAChR system.

  4. Enhancing the versatility of alternate current biosusceptometry (ACB) through the synthesis of a dextrose-modified tracer and a magnetic muco-adhesive cellulose gel

    Energy Technology Data Exchange (ETDEWEB)

    Martins, Murillo L., E-mail: murillolongo@gmail.com [Niels Bohr Institute, University of Copenhagen, DK-2100 Copenhagen (Denmark); Instituto de Biociências, Universidade Estadual Paulista, CP 510, 18618–970 Botucatu SP (Brazil); Calabresi, Marcos F.; Quini, Caio; Matos, Juliana F.; Miranda, José R.A.; Saeki, Margarida J. [Instituto de Biociências, Universidade Estadual Paulista, CP 510, 18618–970 Botucatu SP (Brazil); Bordallo, Heloisa N. [Niels Bohr Institute, University of Copenhagen, DK-2100 Copenhagen (Denmark)

    2015-03-01

    Alternate Current Biosusceptometry (ACB) is a promising bio-magnetic method, radiation free and easily performed used for gastric emptying exams. Due to development on its sensitivity level, interesting nature, noninvasiveness and low cost it has attracted a lot of attention. In this work, magnetic nanoparticles of Mn–Zn ferrite as well as dextrose-modified nanoparticles were synthesized to be used as possible tracers in ACB gastric emptying exams. In addition, a magnetic muco-adhesive gel was obtained by modifying the ferrite nanoparticles with cellulose. Based on in-vivo tests in rats, we show that the pure ferrite nanoparticles, whose isoelectric point was found to be at pH = 3.2, present a great sensitivity to pH variations along the gastrointestinal tract, while the reduction of the isoelectric point by the dextrose modification leads to suitable nanoparticles for rapid gastric emptying examinations. On the other hand, the in-vivo tests show that the muco-adhesive cellulose gel presents substantial stomach adhesion and is a potential drug delivery system easily traceable by the ACB system.

  5. Recruiting the Students to Fight Cancer: Total Synthesis of Goniothalamin

    Science.gov (United States)

    Nahra, Fady; Riant, Olivier

    2015-01-01

    A modified total synthesis of (S)-goniothalamin is described for an advanced course in organic chemistry. This experiment gives students an opportunity to handle organometallic reagents and perform an enzymatic kinetic resolution and a metathesis reaction, all in the same synthesis. Furthermore, students learn flame-drying techniques for the…

  6. Organometallic nucleoside analogues with ferrocenyl linker groups: synthesis and cancer cell line studies.

    Science.gov (United States)

    Nguyen, Huy V; Sallustrau, Antoine; Balzarini, Jan; Bedford, Matthew R; Eden, John C; Georgousi, Niki; Hodges, Nikolas J; Kedge, Jonathan; Mehellou, Youcef; Tselepis, Chris; Tucker, James H R

    2014-07-10

    Examples of organometallic compounds as nucleoside analogues are rare within the field of medicinal bioorganometallic chemistry. We report on the synthesis and properties of two chiral ferrocene derivatives containing a nucleobase and a hydroxyalkyl group. These so-called ferronucleosides show promising anticancer activity, with cytostatic studies on five different cancer cell lines indicating that both functional groups are required for optimal activity.

  7. Synthesis and evaluation of 1'-[[sup 18]F]fluorometoprolol as a potential tracer for the visualization of [beta]-adrenoceptors with PET

    Energy Technology Data Exchange (ETDEWEB)

    Groot, T.J. de; Waarde, A. van; Elsinga, P.H.; Visser, G.M.; Vaalburg, Willem (Groningen Univ. Hospital (Netherlands)); Brodde, O.-E. (Essen Univ. (Germany). Biochemisches Forschungslabor)

    1993-07-01

    ([+-])-1'[[sup 18]F]Fluorometoprol 4 was prepared from desisopropylmetoprolol and [[sup 18]F]fluoroisopropyl tosylate 2 with a radiochemical yield of 2% [corrected for decay to end of bombardment (EOB), synthesis time 90 min]. Synthon 2 was prepared from (S)-1,2-propanediol di(p-toluenesulfonate) in 45% radiochemical yield. Compound 4 shows in two in vitro assays a similar affinity at [beta]-adrenoceptors (about 0.3 [mu]M) as metroprolol 5, but with a slightly higher [beta][sub 1]/[beta][sub 2]-adrenoceptor selectivity ratio (48.6 vs 30.7). In vivo experiments with 4 showed almost no receptor-mediated uptake in the heart probably because the affinity of (fluoro)metoprolol for the [beta][sub 1]-adrenoceptors is too low for successful imaging. However, the in vitro experiments suggest that the fluoroisopropyl group is suitable for the synthesis of [[sup 18]F]fluorinated [beta][sub 1]-adrenergic receptor binding ligands. (Author).

  8. Synthesis of New Anti-Cancer Natural Products

    DEFF Research Database (Denmark)

    Yu, Wanwan

    2016-01-01

    Cancer is one of the leading causes of morbidity and mortality worldwide, and more than 90% of the cancer-related deaths are due to the causes of metastatic pathological change. Tumor hypoxia, resulting from the inadequate blood supply in tumor tissues due to high cellular proliferation, is linked...... given by the inhibitory effects on the HIF-1 transcriptional pathway (STR-2 (1), STR-3 (2), STR-8 (3)), and cancer cell invasion inhibition (STR-8 (3), STR-26 (4)). The mechanistic explanations of these interactions between cancer cell cellular actions and the small natural molecules of the STR family...... have yet to be deduced. This class of marine natural products of meroterpenoids could contribute to the realm of the hypoxia-related cancer research. The complex meroterpenoid framework, stereochemical demands and bicyclic δ-lactone moiety found in most of the bioactive STR molecules, make...

  9. Synthesis of O-(2-[18F]fluoroethyl)-L-tyrosine and its biological evaluation in B16 melanoma-bearing mice as PET tracer for tumor imaging

    Institute of Scientific and Technical Information of China (English)

    WANG MingWei; YIN DuanZhi; LI ShiQiang; WANG YongXian

    2007-01-01

    O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET), a fluorine-18 labeled analogue of tyrosine, has been synthesized and biologically evaluated in tumor-bearing mice. The whole synthesis procedure is completed within 50 min. The radiochemical yield is about 40% (no decay corrected) and radiochemical purity more than 97% after simplified solid phase extraction. [18F]FET shows rapid, high uptake and long retention in the tumor as well as low uptake in the brain. The ratios of tumor-to-muscle (T/M) and tumor-to-blood (T/B) of [18F]FET are similar to those of [18F]FDG, but the ratios of tumor-to-brain (T/Br)are 2-3 times higher than that of [18F]FDG. Autoradiography of [18F]FET demonstrates a remarkable accumulation in melanoma with high contrast. It appears to be a probable competitive candidate for melanoma imaging with PET.

  10. Synthesis of O-(2-[18F]fluoroethyl)-L-tyrosine and its biological evaluation in B16 melanoma-bearing mice as PET tracer for tumor imaging

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    O-(2-[18F]fluoroethyl) -L-tyrosine([18F]FET) ,a fluorine-18 labeled analogue of tyrosine,has been syn-thesized and biologically evaluated in tumor-bearing mice. The whole synthesis procedure is com-pleted within 50 min. The radiochemical yield is about 40%(no decay corrected) and radiochemical purity more than 97% after simplified solid phase extraction. [18F]FET shows rapid,high uptake and long retention in the tumor as well as low uptake in the brain. The ratios of tumor-to-muscle(T/M) and tumor-to-blood(T/B) of [18F]FET are similar to those of [18F]FDG,but the ratios of tumor-to-brain(T/Br) are 2-3 times higher than that of [18F]FDG. Autoradiography of [18F]FET demonstrates a remarkable accumulation in melanoma with high contrast. It appears to be a probable competitive candidate for melanoma imaging with PET.

  11. Journal: Efficient Hydrologic Tracer-Test Design for Tracer ...

    Science.gov (United States)

    Hydrological tracer testing is the most reliable diagnostic technique available for the determination of basic hydraulic and geometric parameters necessary for establishing operative solute-transport processes. Tracer-test design can be difficult because of a lack of prior knowledge of the basic hydraulic and geometric parameters desired and the appropriate tracer mass to release. A new efficient hydrologic tracer-test design (EHTD) methodology has been developed to facilitate the design of tracer tests by root determination of the one-dimensional advection-dispersion equation (ADE) using a preset average tracer concentration which provides a theoretical basis for an estimate of necessary tracer mass. The method uses basic measured field parameters (e.g., discharge, distance, cross-sectional area) that are combined in functional relatipnships that descrive solute-transport processes related to flow velocity and time of travel. These initial estimates for time of travel and velocity are then applied to a hypothetical continuous stirred tank reactor (CSTR) as an analog for the hydrological-flow system to develop initial estimates for tracer concentration, tracer mass, and axial dispersion. Application of the predicted tracer mass with the hydraulic and geometric parameters in the ADE allows for an approximation of initial sample-collection time and subsequent sample-collection frequency where a maximum of 65 samples were determined to be necessary for descri

  12. Tracer tomography (in) rocks!

    Science.gov (United States)

    Somogyvári, Márk; Jalali, Mohammadreza; Jimenez Parras, Santos; Bayer, Peter

    2016-04-01

    Physical behavior of fractured aquifers is rigorously controlled by the presence of interconnected conductive fractures, as they represent the main pathways for flow and transport. Ideally, they are simulated as a discrete fracture network (DFN) in a model to capture the role of fracture system geometry, i.e. fracture length, height, and width (aperture/transmissivity). Such network may be constrained by prior geological information or direct data resources such as field mapping, borehole logging and geophysics. With the many geometric features, however, calibration of a DFN to measured data is challenging. This is especially the case when spatial properties of a fracture network need to be calibrated to flow and transport data. One way to increase the insight in a fractured rock is by combining the information from multiple field tests. In this study, a tomographic configuration that combines multiple tracer tests is suggested. These tests are conducted from a borehole with different injection levels that act as sources. In a downgradient borehole, the tracer is recorded at different levels or receivers, in order to maximize insight in the spatial heterogeneity of the rock. As tracer here we chose heat, and temperature breakthrough curves are recorded. The recorded tracer data is inverted using a novel stochastic trans-dimensional Markov Chain Monte Carlo procedure. An initial DFN solution is generated and sequentially modified given available geological information, such as expected fracture density, orientation, length distribution, spacing and persistency. During this sequential modification, the DFN evolves in a trans-dimensional inversion space through adding and/or deleting fracture segments. This stochastic inversion algorithm requires a large number of thousands of model runs to converge, and thus using a fast and robust forward model is essential to keep the calculation efficient. To reach this goal, an upwind coupled finite difference method is employed

  13. Design and Synthesis of New Breast Cancer Chemotherapeutic Agents

    Science.gov (United States)

    1999-08-01

    of Ingenol," Synlett 1995 , 533-535. 47. H. Li, S. Narasimhulu, L. Havran, J. Winkler, T. Poulos, "Crystal Structure of Cytochrome P-450 Complexed...Müller T: Synlett 1997 1010-1012; b) Furstner A; Langemann K: Synthesis 1997 792-803. [15] Taylor R; Haley H: Tetrahedron Lett. 1997 55:2061-2064 and

  14. Synthesis and biological evaluation of matrine derivatives as anti-hepatocellular cancer agents.

    Science.gov (United States)

    Wu, Lichuan; Liu, Shuaibing; Wei, Jinrui; Li, Dong; Liu, Xu; Wang, Jianyi; Wang, Lisheng

    2016-09-01

    We delineate herein the synthesis and anti-cancer effects of 15 matrine derivatives. The in vitro growth inhibitory assays showed that most of the prepared compounds exhibited improved anti-proliferative activities towards cancer cells with IC50 17-109 times lower than that of matrine. Compounds CH6 showed the most potent anti-proliferative activities in the four tested cancer cell lines. Moreover, compound CH6 could induce G1 cell cycle arrest and inhibit cell migration in human hepatocellular cancer cell lines Bel-7402 and HepG2 through up-regulation of P21, P27 and E-cadherin and down-regulation of N-cadherin.

  15. IND Regulatory & Manufacturing Resources - Cancer Imaging Program

    Science.gov (United States)

    The Cancer Imaging Program has been creating Investigational New Drug Applications (IND) for imaging agents in order to engage in multi-center clinical trials of these materials. A subset of the documents filed is being made available to the research community to implement routine synthesis of tracers at their own facilities and to assist investigators with the filing of their own INDs. The first of these document sets is for F-18 fluorothymidine (FLT).

  16. Development of radioisotope tracer technology

    Energy Technology Data Exchange (ETDEWEB)

    Jin, Joon Ha; Lee, Myun Joo; Jung, Sung Hee; Park, Soon Chul; Lim, Dong Soon; Kim, Jae Ho; Lee, Jae Choon; Lee, Doo Sung; Cho, Yong Suk; Shin, Sung Kuan

    2000-04-01

    The purpose of this study is to develop the radioisotope tracer technology, which can be used in solving industrial and environmental problems and to build a strong tracer group to support the local industries. In relation to the tracer technology in 1999, experiments to estimate the efficiencies of a sludge digester of a waste water treatment plant and a submerged biological reactor of a dye industry were conducted. As a result, the tracer technology for optimization of facilities related to wastewater treatment has been developed and is believed to contribute to improve their operation efficiency. The quantification of the experimental result was attempted to improve the confidence of tracer technology by ECRIN program which basically uses the MCNP simulation principle. Using thin layer activation technique, wear of tappet shim was estimated. Thin layer surface of a tappet shim was irradiated by proton beam and the correlation between the measured activity loss and the amount of wear was established. The equipment was developed to adjust the energy of proton which collides with the surface of tappet. The tracer project team has participated into the tracer test for estimating the efficiency of RFCC system in SK cooperation. From the experiment the tracer team has obtained the primary elements to be considered for judging the efficiency of RFCC unit. By developing the tracer techniques to test huge industrial units like RFCC, the tracer team will be able to support the local industries that require technical services to solve any urgent trouble. (author)

  17. Design, synthesis and in vitro evaluation of novel anti-cancer compounds

    OpenAIRE

    McCormack, Emmet Martin

    2003-01-01

    The purpose of this thesis was the design, synthesis and in vitro appraisal of a novel class of ITP/APN dual inhibitory compounds. Additionally, a class of novel biaryls, which were synthesised within the research group, were assayed to evaluate their ability to inhibit tubulin polymerisation (ITP). The introductory chapter commences with brief overview of the history of cancer and role of natural products in conventional chemotherapeutic regimes and adjuvant immunotherapies. Subsequently, th...

  18. The synthesis and evaluation of N{sup 1}-(4-(2-[{sup 18}F]-fluoroethyl)phenyl)-N{sup 8}-hydroxyoctanediamide ([{sup 18}F]-FESAHA), A PET radiotracer designed for the delineation of histone deacetylase expression in cancer

    Energy Technology Data Exchange (ETDEWEB)

    Zeglis, Brian M.; Pillarsetty, NagaVaraKishore; Divilov, Vadim [Radiochemistry Service, Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021 (United States); Blasberg, Ronald A. [Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021 (United States); Lewis, Jason S., E-mail: lewisj2@mskcc.org [Radiochemistry Service, Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021 (United States); Program in Molecular Pharmacology and Chemistry, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, NY 10021 (United States)

    2011-07-15

    Introduction: Given the significant utility of suberoylanilide hydroxamic acid (SAHA) in chemotherapeutic protocols, a PET tracer that mimics the histone deacetylase (HDAC) inhibition of SAHA could be a valuable tool in the diagnosis, treatment planning and treatment monitoring of cancer. Here, we describe the synthesis, characterization and evaluation of N{sup 1}-(4-(2-[{sup 18}F]-fluoroethyl)phenyl)-N{sup 8}-hydroxyoctanediamide ([{sup 18}F]-FESAHA), a PET tracer designed for the delineation of HDAC expression in cancer. Methods: FESAHA was synthesized and biologically characterized in vivo and in vitro. [{sup 18}F]-FESAHA was then synthesized in high radiochemical purity, and the logP and serum stability of the radiotracer were determined. In vitro cellular uptake experiments and acute biodistribution and small-animal PET studies were performed with [{sup 18}F]-FESAHA in mice bearing LNCaP xenografts. Results: [{sup 18}F]-FESAHA was synthesized in high radiochemical purity via an innovative one-pot procedure. Enzymatic inhibition assays illustrated that FESAHA is a potent HDAC inhibitor, with IC{sub 50} values from 3 nM to 1.7 {mu}M against the 11 HDAC subtypes. Cell proliferation experiments revealed that the cytostatic properties of FESAHA very closely resemble those of SAHA in both LNCaP cells and PC-3 cells. Acute biodistribution and PET imaging experiments revealed tumor uptake of [{sup 18}F]-FESAHA and substantially higher values in the small intestine, kidneys, liver and bone. Conclusion: The significant non-tumor background uptake of [{sup 18}F]-FESAHA presents a substantial obstacle to the use of the radiotracer as an HDAC expression imaging agent. The study at hand, however, does present a number of lessons critical to both the synthesis of hydroxamic acid containing PET radiotracers and imaging agents aimed at delineating HDAC expression.

  19. Usage of nano carbon tracer technology in colorectal cancer radical mastectomy%纳米活性炭示踪技术在直肠癌根治术中的应用价值

    Institute of Scientific and Technical Information of China (English)

    李炳强; 李豫江; 李志刚; 丁元升; 孙旭凌; 祝磊; 黄桂林

    2012-01-01

    目的 探讨纳米活性炭示踪技术在直肠癌根治术中的临床应用价值.方法 43例直肠癌患者随机分为纳米炭组20例和对照组23例,比较两组检获的淋巴结数、黑染淋巴结数及病理证实淋巴结癌转移情况.结果 两组共检获淋巴结670枚,纳米炭组(20.40 ±7.61)枚/例;显著高于对照组的(11.39 ±5.32)枚/例,P<0.01.纳米炭组检获黑染淋巴结302枚中,癌转移淋巴结40枚;未黑染淋巴结106枚中,癌转移淋巴结6枚.对照组检获262枚淋巴结中,癌转移淋巴结26枚.黑染的淋巴结中癌转移率更高(P<0.05).结论 在直肠癌根治术中采用纳米活性炭示踪技术可提高直肠癌根治术患者淋巴结检获数量和直肠癌病理分期的准确性,对直肠癌淋巴结清扫有一定指导作用.%Objective To investigate the clinical application value of nano carbon tracer technology in colorectal cancer radical mastectomy. Methods A total of 43 patients with colorectal cancer were randomly divided into nanometer carbon group of 20 cases and control group of 23 cases to compare seized lymph node number, black dye lymph node number and pathology confirmed carcinoma metastasis lymph node situation. Results There were 670 pieces of lymph node seized in two groups toally, including (20. 4 ± 7. 61) medals/case in nano carbon group and (11. 39 ± 5. 32) medals/case in control group. Lymph node number in nano carbon group was more than control group (P<0.05). In nano carbon group, the number of black dye lymph node was 302 including 40 pieces of cancer metastasis lymph node, while the non-black dye lymph node was 106 including 6 pieces of cancer metastasis lymph node. There was 26 pieces of cancer metastasis lymph node seized in all 262 pieces of lymph nodes in control group. The metastasis rate of black dye lymph node was higher ( P < 0. 05 ) . Conclusions The usage of nano carbon tracer can improve the number of lymph node in colorectal cancer radical mastctomy

  20. Gluconeogenesis, liver energy metabolism and weight loss in lung cancer : dynamic studies using stable isotope tracers and 31P magnetic resonance spectroscopy

    NARCIS (Netherlands)

    S. Leij-Halfwerk (Susanne)

    1999-01-01

    textabstractWeight loss is a major problem in many types of cancer and is associated with reduced quality of life and a poor prognosis. Weight loss can also interfere with potentially curable treatment [41,561. Many uncertainties remain about the mechanisms underlying weight loss in patients with ca

  1. Engineered magnetic core shell nanoprobes:Synthesis and applications to cancer imaging and therapeutics

    Institute of Scientific and Technical Information of China (English)

    Samir Mandal; Keya Chaudhuri

    2016-01-01

    Magnetic core shell nanoparticles are composed of a highly magnetic core material surrounded by a thin shell of desired drug, polymer or metal oxide. These magnetic core shell nanoparticles have a wide range of applications in biomedical research, more specifically in tissue imaging, drug delivery and therapeutics. The present review discusses the up-to-date knowledge on the various procedures for synthesis of magnetic core shell nanoparticles along with their applications in cancer imaging, drug delivery and hyperthermia or cancer therapeutics. Literature in this area shows that magnetic core shell nanoparticle-based imaging, drug targeting and therapy through hyperthermia can potentially be a powerful tool for the advanced diagnosis and treatment of various cancers.

  2. Engineered magnetic core shell nanoprobes: Synthesis and applications to cancer imaging and therapeutics.

    Science.gov (United States)

    Mandal, Samir; Chaudhuri, Keya

    2016-02-26

    Magnetic core shell nanoparticles are composed of a highly magnetic core material surrounded by a thin shell of desired drug, polymer or metal oxide. These magnetic core shell nanoparticles have a wide range of applications in biomedical research, more specifically in tissue imaging, drug delivery and therapeutics. The present review discusses the up-to-date knowledge on the various procedures for synthesis of magnetic core shell nanoparticles along with their applications in cancer imaging, drug delivery and hyperthermia or cancer therapeutics. Literature in this area shows that magnetic core shell nanoparticle-based imaging, drug targeting and therapy through hyperthermia can potentially be a powerful tool for the advanced diagnosis and treatment of various cancers.

  3. Facile Synthesis of Biocompatible Fluorescent Nanoparticles for Cellular Imaging and Targeted Detection of Cancer Cells.

    Science.gov (United States)

    Tang, Fu; Wang, Chun; Wang, Xiaoyu; Li, Lidong

    2015-11-18

    In this work, we report the facile synthesis of functional core-shell structured nanoparticles with fluorescence enhancement, which show specific targeting of cancer cells. Biopolymer poly-l-lysine was used to coat the silver core with various shell thicknesses. Then, the nanoparticles were functionalized with folic acid as a targeting agent for folic acid receptor. The metal-enhanced fluorescence effect was observed when the fluorophore (5-(and-6)-carboxyfluorescein-succinimidyl ester) was conjugated to the modified nanoparticle surface. Cellular imaging assay of the nanoparticles in folic acid receptor-positive cancer cells showed their excellent biocompatibility and selectivity. The as-prepared functional nanoparticles demonstrate the efficiency of the metal-enhanced fluorescence effect and provide an alternative approach for the cellular imaging and targeting of cancer cells.

  4. Microfluidics: A Groundbreaking Technology for PET Tracer Production?

    Directory of Open Access Journals (Sweden)

    Björn Wängler

    2013-07-01

    Full Text Available Application of microfluidics to Positron Emission Tomography (PET tracer synthesis has attracted increasing interest within the last decade. The technical advantages of microfluidics, in particular the high surface to volume ratio and resulting fast thermal heating and cooling rates of reagents can lead to reduced reaction times, increased synthesis yields and reduced by-products. In addition automated reaction optimization, reduced consumption of expensive reagents and a path towards a reduced system footprint have been successfully demonstrated. The processing of radioactivity levels required for routine production, use of microfluidic-produced PET tracer doses in preclinical and clinical imaging as well as feasibility studies on autoradiolytic decomposition have all given promising results. However, the number of microfluidic synthesizers utilized for commercial routine production of PET tracers is very limited. This study reviews the state of the art in microfluidic PET tracer synthesis, highlighting critical design aspects, strengths, weaknesses and presenting several characteristics of the diverse PET market space which are thought to have a significant impact on research, development and engineering of microfluidic devices in this field. Furthermore, the topics of batch- and single-dose production, cyclotron to quality control integration as well as centralized versus de-centralized market distribution models are addressed.

  5. Radon as geological tracer

    Energy Technology Data Exchange (ETDEWEB)

    Lacerda, T.; Anjos, R.M. [Universidade Federal Fluminense (UFF), Niteroi, RJ (Brazil). Inst. de Fisica; Valladares, D.L.; Rizzotto, M.; Velasco, H.; Ayub, J. Juri [Universidad Nacional de San Luis (Argentina). Inst. de Matematica Aplicada San Luis (IMASL); Silva, A.A.R. da; Yoshimura, E.M. [Universidade de Sao Paulo (IF/USP), SP (Brazil). Inst. de Fisica

    2012-07-01

    Full text: This work presents measurements of {sup 222}Rn levels performed in La Carolina gold mine and Los Condores tungsten mine at the province of San Luis, Argentina, today used for tourist visitation, and can evaluate the potential use of such radioactive noble gas as tracer or marker for geological processes in underground environments. By concentrations of {sup 40}K, {sup 232}Th and {sup 23}'8U were also measured in the walls of tunnels were determined the rocks mineral composition, what indicated that the mines have the same composition. In this sense, we used nuclear trace plastic detectors CR-39, gamma spectrometry of rock samples and Geiger-Muller (GM) monitors The patterns of radon gas transportation processes revealed that La Carolina could be interpreted through a model based on a radioactive gas confined into a single entrance tube, with constant cross section and air velocity. Los Condores, which has a second main entrance, could be interpreted through a model based on a radioactive gas confined into a two entrance tube, allowing a chimney effect for air circulation. The results showed the high potential of using {sup 222}Rn as a geological tracer. In what concerns the occupational hazard, in summer (time of more intense tourist activity in the mine) La Carolina presented a mean concentration of the radioactive noble gas that exceeds in four times the action level of 1,5 kBq m{sup -3} recommended by the International Commission of Radiological Protection (ICRP). The chimney effect shows the low mean concentration of radon in Los Condores. (author)

  6. Uptake of algal carbon and the synthesis of an "essential" fatty acid by Uvigerina ex. gr. semiornata (Foraminifera within the Pakistan margin oxygen minimum zone: evidence from fatty acid biomarker and 13C tracer experiments

    Directory of Open Access Journals (Sweden)

    K. E. Larkin

    2014-01-01

    Full Text Available Foraminifera are an important component of benthic communities in oxygen depleted settings, where they potentially play a~significant role in the processing of organic matter. We tracked the uptake of a 13C-labeled algal food source into individual fatty acids in the benthic foraminiferal species, Uvigerina ex. gr. semiornata, from the Arabian Sea oxygen minimum zone (OMZ. The tracer experiments were conducted on the Pakistan Margin during the late/post monsoon period (August–October 2003. A monoculture of the diatom Thalassiosira weisflogii was 13C-labeled and used to simulate a pulse of phytoplankton in two complementary experiments. A lander system was used for in situ incubations at 140 m and for 2.5 days duration, whilst a laboratory incubation used an oxystat system to maintain ambient dissolved oxygen concentrations. These shipboard experiments were terminated after 5 days. Uptake of diatoms was rapid, with high incorporation of diatom fatty acids into foraminifera after ~2 days in both experiments. Ingestion of the diatom food source was indicated by the increase over time in the quantity of diatom biomarker fatty acids in the foraminifera and by the high percentage of 13C in many of the fatty acids present at the endpoint of both in~situ and laboratory-based experiments. These results indicate that U. ex. gr. semiornata rapidly ingested the diatom food source and that this foraminifera will play an important role in the short-term cycling of organic matter within this OMZ environment. The experiments also suggested that U. ex. gr. semiornata consumed non-labeled bacterial food items, particularly bacteria, and synthesised the polyunsaturated fatty acid 20:4(n-6 de novo. 20:4(n-6 is often abundant in benthic fauna yet its origins and function have remained unclear. This study demonstrates that U. ex. gr. semiornata is capable of de novo synthesis of this "essential fatty acid" and is potentially a major source of this dietary nutrient

  7. Synthesis of Multifunctional Nanoparticles for Cancer Diagnostics and Therapeutics

    Science.gov (United States)

    Fang, Chen

    2011-12-01

    Magnetic nanoparticles (MNPs) have attracted enormous research attention due to their unique magnetic properties that enable the detection by the non-invasive medical imaging modality---magnetic resonance imaging (MRI). By incorporating advanced features, such as specific targeting, multimodality, therapeutic delivery, the detectability and applicability of MNPs have been dramatically expanded. Smart and rational design on structure, composition and surface chemistry is essential to achieving desired properties in MNP systems, such as high sensitivity and colloidal stability, target specificity and/or multimodality. The goal of this research is to develop MNP-based platforms for the detection, diagnosis and treatment of cancer. MNPs with high contrast enhancement were coated with poly(ethylene glycol) (PEG)-based polymers to render aqueous stability and confer therapeutic-loading capability. Tumor-specific MNPs were developed by functionalization of nanoparticles with chlorotoxin (CTX) or arginine-glycine-aspartic acid (RGD) that targets, respectively, MMP-2 receptor or alphavbeta3 integrin overexpressed on a variety of cancer cells. The effects of ligands' molecular targets on the temporal and spatial distribution of MNPs within tumors were also investigated both in vitro and in vivo. All MNPs exhibited excellent long-term stability in cell culture media. CTX-labeled MNP exhibited sustained accumulation, penetration and distribution in the tumor mass. These findings revealed the influence of the targeting ligands on the intratumoral distribution of the ligand-enabled nanoprobes. To demonstrate the ability of nanoparticles as drug carrier, anthracyline chemotherapeutic drugs doxorubicin and mitoxantrone were attached to iron oxide nanoparticles. The theragnostic nanoparticles showed sufficient contrast enhancement and comparable anti-neoplastic efficacy in vitro. With flexible surface chemistry, our nanoparticle platform can be used in a modular fashion to

  8. Exotic tracers for atmospheric studies

    Energy Technology Data Exchange (ETDEWEB)

    Lovelock, J.E. (Brazzos Ltd., Launceston (UK)); Ferber, G.J. (National Oceanic and Atmospheric Administration, Silver Spring, MD (USA). Air Resources Lab.)

    1982-01-01

    Tracer materials can be injected into the atmosphere to study transport and dispersion processes and to validate air pollution model calculations. Tracers should be inert, non-toxic and harmless to the environment. Tracers for long-range experiments, where dilution is very great, must be measurable at extremely low concentrations, well below the parts per trillion level. Compounds suitable for long-range tracer work are rare and efforts should be made to reserve them for meteorological studies, barring them from commercial uses which would increase atmospheric background concentrations. The use of these exotic tracers, including certain perfluorocarbons and isotopically labelled methanes, should be coordinated within the meteorological community to minimize interferences and maximise research benefits.

  9. Exotic tracers for atmospheric studies

    Science.gov (United States)

    Lovelock, James E.; Ferber, Gilbert J.

    Tracer materials can be injected into the atmosphere to study transport and dispersion processes and to validate air pollution model calculations. Tracers should be inert, non-toxic and harmless to the environment. Tracers for long-range experiments, where dilution is very great, must be measurable at extremely low concentrations, well below the parts per trillion level. Compounds suitable for long-range tracer work are rare and efforts should be made to reserve them for meteorological studies, barring them from commercial uses which would increase atmospheric background concentrations. The use of these exotic tracers, including certain perfluorocarbons and isotopically labelled methanes, should be coordinated within the meteorological community to minimize interferences and maximize research benefits.

  10. Living with Malignant Wound in Cancer Patients and Adolescents with Non- Cancer Diagnosis: a Meta-Synthesis of Qualitative Studies

    Directory of Open Access Journals (Sweden)

    Ali Reza Mansourzadeh

    2016-09-01

    Full Text Available Background Malignant wound causes a devastating physical and psychological condition in cancer patients. This study presents a review which can provide better insights into the life of cancer patients living with malignant wound. The aim of this meta-synthesis was to analyze and synthesize findings from qualitative studies of the lived experiences of patients with malignant wound. Materials and Methods This meta-synthesis followed the Sandelowski and Barroso’s guideline and was designed to synthesize findings from previous qualitative studies. Variety of biomedical archives were searched, including PubMed, Web of Science, PsycINFO, Cochrane library, and ProQuest and Persian data bases such as Magiran, SID, Iran.doc, IranMedex, and  recently published articles and books on the lived experience of persons living with malignant wound were reviewed. In this article, the literature searches covering from January,1, 1990 to march,15, 2016 resulted in eight relevant studies which fulfilled the inclusion criteria for the review. Results Findings from all these studies were categorized into three main themes: "distortion of lived body", "symptomatic suffering", and "compatible living with wound". Our findings showed that the meanings of patients’ experiences living with malignant wound are important for the construction of multidisciplinary palliative care in these individuals. Conclusion: Gaining insights from analysis of qualitative studies is integral issue for developing new palliative care services for patients with malignant wound.

  11. In vitro and in vivo targeting of different folate receptor-positive cancer cell lines with a novel {sup 99m}Tc-radiofolate tracer

    Energy Technology Data Exchange (ETDEWEB)

    Mueller, Cristina [Paul Scherrer Institute, Center for Radiopharmaceutical Science ETH-PSI-USZ, Villigen-PSI (Switzerland); Schubiger, P.A.; Schibli, Roger [Paul Scherrer Institute, Center for Radiopharmaceutical Science ETH-PSI-USZ, Villigen-PSI (Switzerland); Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, ETH Zurich, Zurich (Switzerland)

    2006-10-15

    For the assessment of folate-based radiopharmaceuticals, human nasopharyngeal KB carcinoma cells are traditionally used although nasopharyngeal cancer is rare. On the other hand, the folate receptor (FR) is frequently overexpressed on diverse cancer types, the highest frequency (>90%) being on ovarian carcinomas. The goal of our study was the in vitro and in vivo assessment of different FR-positive human carcinoma cells. In addition, a murine sarcoma cell line was assessed as a pre-clinical alternative to human xenograft models. FR-positive human nasopharyngeal, cervical, ovarian and colorectal cancer cell lines and the transgenic mouse sarcoma (24JK-FBP) cell line were targeted with a novel {sup 99m}Tc-tricarbonyl folate derivative 2. Comparative in vitro cell binding studies were carried out under standardised folate-deficient conditions. In vivo studies were performed in nude mice and C6 black mice. The in vitro cell experiments revealed only FR-specific binding (unspecific <0.02%), ranging from 3.5% to 52% of complex 2 owing to variable levels of FR expression of the cell lines. In vivo tumour uptake of radiotracer 2 varied less than in vitro. It ranged from 0.66{+-}0.17% ID/g (LoVo) through 1.16{+-}0.64% ID/g (IGROV-1) and 1.55{+-}0.43% ID/g (24JK-FBP) to 2.33{+-}0.36% ID/g (KB) 4 h p.i. These pre-clinical studies indicate that in vitro data obtained in FR-positive cancer cells do not necessarily correspond with or predict in vivo radiofolate uptake in corresponding (xeno)grafts. In addition, the murine 24JK-FBP cell line proved to be a valuable pre-clinical alternative to human tumour models. (orig.)

  12. The primary care provider (PCP)-cancer specialist relationship: A systematic review and mixed-methods meta-synthesis.

    Science.gov (United States)

    Dossett, Lesly A; Hudson, Janella N; Morris, Arden M; Lee, M Catherine; Roetzheim, Richard G; Fetters, Michael D; Quinn, Gwendolyn P

    2017-03-01

    Although they are critical to models of coordinated care, the relationship and communication between primary care providers (PCPs) and cancer specialists throughout the cancer continuum are poorly understood. By using predefined search terms, the authors conducted a systematic review of the literature in 3 databases to examine the relationship and communication between PCPs and cancer specialists. Among 301 articles identified, 35 met all inclusion criteria and were reviewed in-depth. Findings from qualitative, quantitative, and disaggregated mixed-methods studies were integrated using meta-synthesis. Six themes were identified and incorporated into a preliminary conceptual model of the PCP-cancer specialist relationship: 1) poor and delayed communication between PCPs and cancer specialists, 2) cancer specialists' endorsement of a specialist-based model of care, 3) PCPs' belief that they play an important role in the cancer continuum, 4) PCPs' willingness to participate in the cancer continuum, 5) cancer specialists' and PCPs' uncertainty regarding the PCP's oncology knowledge/experience, and 6) discrepancies between PCPs and cancer specialists regarding roles. These data indicate a pervasive need for improved communication, delineation, and coordination of responsibilities between PCPs and cancer specialists. Future interventions aimed at these deficiencies may improve patient and physician satisfaction and cancer care coordination. CA Cancer J Clin 2017;67:156-169. © 2016 American Cancer Society.

  13. Sentinel lymph node biopsy in breast cancer--experience with the combined use of dye and radioactive tracer at Aarhus University Hospital

    DEFF Research Database (Denmark)

    Lauridsen, Mette Cathrine; Garne, Jens Peter; Sørensen, Flemming Brandt;

    2004-01-01

    -needle aspiration biopsy (FNAB) were not included. For identifying the SLNs, a combination of Tc-99m-labelled human albumin (Solco-ALBU-RES) and blue dye (Patent Blue V) was used. No lymphoscintigraphy was performed. The SLN was successfully identified in 122 out of 124 (98%) patients and 66 (54%) patients were...... found to have metastatic involvement of the axillary lymph nodes. In 52 (79%) of these patients, the SLNs were the only nodes involved, 28 (54%) had micrometastasis only. The false-negative rate was 1.5%. This method has proven valid in the staging of the axilla in patients with breast cancer...

  14. CONVERGENT SYNTHESIS AND EVALUATION OF 18F-LABELED AZULENIC COX2 PROBES FOR CANCER IMAGING

    Directory of Open Access Journals (Sweden)

    Donald D. Nolting

    2013-01-01

    Full Text Available The overall objectives of this research are to (i develop azulene-based PET probes and (ii image COX2 as a potential biomarker of breast cancer. Several lines of research have demonstrated that COX2 is overexpressed in breast cancer and that its presence correlates with poor prognoses. While other studies have reported that COX2 inhibition can be modulated and used beneficially as a chemopreventive strategy in cancer, no viable mechanism for achieving that approach has yet been developed. This shortfall could be circumvented through in vivo imaging of COX2 activity, particularly using sensitive imaging techniques such as PET. Toward that goal, our laboratory focuses on the development of novel 18F-labled COX2 probes. We began the synthesis of the probes by transforming tropolone into a lactone, which was subjected to an [8+2] cycloaddition reaction to yield 2-methylazulene as the core ring of the probe. After exploring numerous synthetic routes, the final target molecule and precursor PET compounds were prepared successfully using convergent synthesis. Conventional 18F labeling methods caused precursor decomposition, which prompted us to hypothesize that the acidic protons of the methylene moiety between the azulene and thiazole rings were readily abstracted by a strong base such as potassium carbonate. Ultimately, this caused the precursors to disintegrate. This observation was supported after successfully using an 18F labeling strategy that employed a much milder phosphate buffer. The 18F-labeled COX2 probe was tested in a breast cancer xenograft mouse model. The data obtained via successive whole-body PET/CT scans indicated probe accumulation and retention in the tumor. Overall, the probe was stable in vivo and no defluorination was observed. A biodistribution study and Western blot analysis corroborate with the imaging data. In conclusion, this novel COX2 PET probe was shown to be a promising agent for cancer imaging and deserves further

  15. Meta-synthesis exploring barriers to health seeking behaviour among Malaysian breast cancer patients.

    Science.gov (United States)

    Yu, Foo Qing; Murugiah, Muthu Kumar; Khan, Amer Hayat; Mehmood, Tahir

    2015-01-01

    Barriers to health seeking constitute a challenging issue in the treatment of breast cancer. The current meta- synthesis aimed to explore common barriers to health seeking among Malaysian breast cancer patients. From the systematic search, nine studies were found meeting the inclusion criteria. Data extraction revealed that health behavior towards breast cancer among Malaysia women was influenced by knowledge, psychological, sociocultural and medical system factors. In terms of knowledge, most of the Malaysian patients were observed to have cursory information and the reliance on the information provided by media was limiting. Among psychological factors, stress and sense of denial were some of the common factors leading to delay in treatment seeking. Family member's advice, cultural beliefs towards traditional care were some of the common sociocultural factors hindering immediate access to advanced medical diagnosis and care. Lastly, the delay in referral was one of the most common health system-related problems highlighted in most of the studies. In conclusion, there is an immediate need to improve the knowledge and understanding of Malaysian women towards breast cancer. Mass media should liaise with the cancer specialists to disseminate accurate and up-to-date information for the readers and audience, helping in modification of cultural beliefs that hinder timing health seeking. However, such intervention will not improve or rectify the health system related barriers to treatment seeking. Therefore, there is an immediate need for resource adjustment and training programs among health professional to improve their competency and professionalism required to develop an efficient health system.

  16. Proceedings of the atmospheric tracers and tracer application workshop

    Energy Technology Data Exchange (ETDEWEB)

    Barr, S.; Gedayloo, T. (comps.)

    1979-12-01

    In addition to presentations by participating members a general discussion was held in order to summarize and outline the goals and objectives of the workshop. A number of new low level background tracers such as heavy methanes, perfluorocarbons, multiply labeled isotopes such as /sup 13/C/sup 18/O/sub 2/, helium 3, in addition to sample collection techniques and analytical methods for various tracers were discussed. This report is a summary of discussions and papers presented at this workshop.

  17. Cancer

    Science.gov (United States)

    ... cancer Non-Hodgkin lymphoma Ovarian cancer Pancreatic cancer Testicular cancer Thyroid cancer Uterine cancer Symptoms Symptoms of cancer ... tumor Obesity Pancreatic cancer Prostate cancer Stomach cancer Testicular cancer Throat or larynx cancer Thyroid cancer Patient Instructions ...

  18. Glyphosate and AMPA inhibit cancer cell growth through inhibiting intracellular glycine synthesis

    Directory of Open Access Journals (Sweden)

    Li Q

    2013-07-01

    Full Text Available Qingli Li,1,2 Mark J Lambrechts,1 Qiuyang Zhang,1 Sen Liu,1 Dongxia Ge,1 Rutie Yin,2 Mingrong Xi,2 Zongbing You1 1Departments of Structural and Cellular Biology and Orthopaedic Surgery, Tulane Cancer Center and Louisiana Cancer Research Consortium, Tulane Center for Stem Cell Research and Regenerative Medicine, and Tulane Center for Aging, Tulane University Health Sciences Center, New Orleans, LA, USA; 2Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, People’s Republic of China Abstract: Glycine is a nonessential amino acid that is reversibly converted from serine intracellularly by serine hydroxymethyltransferase. Glyphosate and its degradation product, aminomethylphosphonic acid (AMPA, are analogs to glycine, thus they may inhibit serine hydroxymethyltransferase to decrease intracellular glycine synthesis. In this study, we found that glyphosate and AMPA inhibited cell growth in eight human cancer cell lines but not in two immortalized human normal prostatic epithelial cell lines. AMPA arrested C4-2B and PC-3 cancer cells in the G1/G0 phase and inhibited entry into the S phase of the cell cycle. AMPA also promoted apoptosis in C4-2B and PC-3 cancer cell lines. AMPA upregulated p53 and p21 protein levels as well as procaspase 9 protein levels in C4-2B cells, whereas it downregulated cyclin D3 protein levels. AMPA also activated caspase 3 and induced cleavage of poly (adenosine diphosphate [ADP]-ribose polymerase. This study provides the first evidence that glyphosate and AMPA can inhibit proliferation and promote apoptosis of cancer cells but not normal cells, suggesting that they have potentials to be developed into a new anticancer therapy. Keywords: serine hydroxymethyltransferase, prostate cancer, apoptosis

  19. Synthesis and Bioevaluation of Some Phenolic Diarylpropanes as Anti-Cancer Agents

    Directory of Open Access Journals (Sweden)

    Kshama Kundu

    2014-09-01

    Full Text Available A convenient synthesis of six phenolic diarylpropanes has been formulated. A CuBr 2-catalyzed regioselective reaction was the key step for bromination of the arylpropanes. All the compounds showed good cytotoxicity to the human lung cancer A549 cell line. However, only one of these compounds induced apoptosis and a G1 cell cycle arrest by augmenting cellular ROS status. Introduction of bromo-substitution at the aryl groups increased the cytotoxicity significantly, but that was mainly due to necrosis.

  20. Driven tracers in narrow channels

    Science.gov (United States)

    Cividini, J.; Mukamel, D.; Posch, H. A.

    2017-01-01

    Steady-state properties of a driven tracer moving in a narrow two-dimensional (2D) channel of quiescent medium are studied. The tracer drives the system out of equilibrium, perturbs the density and pressure fields, and gives the bath particles a nonzero average velocity, creating a current in the channel. Three models in which the confining effect of the channel is probed are analyzed and compared in this study: the first is the simple symmetric exclusion process (SSEP), for which the stationary density profile and the pressure on the walls in the frame of the tracer are computed. We show that the tracer acts like a dipolar source in an average velocity field. The spatial structure of this 2D strip is then simplified to a one-dimensional (1D) SSEP, in which exchanges of position between the tracer and the bath particles are allowed. Using a combination of mean-field theory and exact solution in the limit where no exchange is allowed gives good predictions of the velocity of the tracer and the density field. Finally, we show that results obtained for the 1D SSEP with exchanges also apply to a gas of overdamped hard disks in a narrow channel. The correspondence between the parameters of the SSEP and of the gas of hard disks is systematic and follows from simple intuitive arguments. Our analytical results are checked numerically.

  1. Comparison of three magnetic nanoparticle tracers for sentinel lymph node biopsy in an in vivo porcine model

    Directory of Open Access Journals (Sweden)

    Pouw JJ

    2015-02-01

    Full Text Available Joost J Pouw,1,* Muneer Ahmed,2,* Bauke Anninga,2 Kimberley Schuurman,1 Sarah E Pinder,2 Mieke Van Hemelrijck,3 Quentin A Pankhurst,4,5 Michael Douek,2 Bennie ten Haken1 1MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, the Netherlands; 2Research Oncology, Division of Cancer Studies, King’s College London, Guy’s Hospital, London, UK; 3Cancer Epidemiology Group, Division of Cancer Studies, King’s College London, London, UK; 4Healthcare Biomagnetics Laboratory, University College London, London, UK; 5Institute of Biomedical Engineering, University College London, London, UK *These authors contributed equally to this work Introduction: Breast cancer staging with sentinel lymph node biopsy relies on the use of radioisotopes, which limits the availability of the procedure worldwide. The use of a magnetic nanoparticle tracer and a handheld magnetometer provides a radiation-free alternative, which was recently evaluated in two clinical trials. The hydrodynamic particle size of the used magnetic tracer differs substantially from the radioisotope tracer and could therefore benefit from optimization. The aim of this study was to assess the performance of three different-sized magnetic nanoparticle tracers for sentinel lymph node biopsy within an in vivo porcine model.Materials and methods: Sentinel lymph node biopsy was performed within a validated porcine model using three magnetic nanoparticle tracers, approved for use in humans (ferumoxytol, with hydrodynamic diameter dH =32 nm; Sienna+®, dH =59 nm; and ferumoxide, dH =111 nm, and a handheld magnetometer. Magnetometer counts (transcutaneous and ex vivo, iron quantification (vibrating sample magnetometry, and histopathological assessments were performed on all ex vivo nodes.Results: Transcutaneous “hotspots” were present in 12/12 cases within 30 minutes of injection for the 59 nm tracer, compared to 7/12 for the 32 nm tracer and 8/12 for

  2. Tracer Diffusion in a Soft Glassy Material

    Science.gov (United States)

    Petit, Laure; Barentin, Catherine; Colombani, Jean; Ybert, Christophe; Barrat, Jean-Louis; Bocquet, Lydéric

    2008-07-01

    We have carried out Fluorescence Recovery After Photobleaching measurements of the diffusion of tracers of various sizes in a colloidal glass (a Laponite suspension). We have shown that the diffusion is only dependent on the ratio of the tracer size and the distance between Laponite disks. This suggests that the tracer diffusion hindrance in the glass stems from the hydrodynamical interactions between the tracer and the Laponite network, the physico-chemical Laponite-tracer interaction playing a negligible role.

  3. C-11 radiochemistry in cancer imaging applications.

    Science.gov (United States)

    Tu, Z; Mach, R H

    2010-01-01

    Carbon-11 (C-11) radiotracers are widely used for the early diagnosis of cancer, monitoring therapeutic response to cancer treatment, and pharmacokinetic investigations of anticancer drugs. PET imaging permits non-invasive monitoring of metabolic processes and molecular targets, while carbon-11 radiotracers allow a "hot-for cold" substitution of biologically active molecules. Advances in organic synthetic chemistry and radiochemistry as well as improved automated techniques for radiosynthesis have encouraged investigators in developing carbon-11 tracers for use in oncology imaging studies. The short half-life of carbon-11 (20.38 minutes) creates special challenges for the synthesis of C-11 labeled tracers; these include the challenges of synthesizing C-11 target compounds with high radiochemical yield, high radiochemical purity and high specific activity in a short time and on a very small scale. The optimization of conditions for making a carbon-11 tracer include the late introduction of the C-11 isotope, the rapid formation and purification of the target compound, and the use of automated systems to afford a high yield of the target compound in a short time. In this review paper, we first briefly introduce some basic principles of PET imaging of cancer; we then discuss principles of carbon-11 radiochemistry, focus on specific advances in radiochemistry, and describe the synthesis of C-11 radiopharmaceuticals developed for cancer imaging. The carbon-11 radiochemistry approaches described include the N,O, and S-alkylations of [(11)C]methyl iodide/[(11)C]methyl triflate and analogues of [(11)C]methyl iodide and their applications for making carbon-11 tracers; we then address recent advances in exploring a transmetallic complex mediated [(11)C]carbonyl reaction for oncologic targets.

  4. Synthesis and Structure-Activity Relationship of Griseofulvin Analogues as Inhibitors of Centrosomal Clustering in Cancer Cells

    DEFF Research Database (Denmark)

    Rønnest, Mads Holger; Rebacz, Blanka; Markworth, Lene

    2009-01-01

    Griseofulvin was identified as an inhibitor of centrosomal clustering in a recently developed assay. Centrosomal clustering is an important cellular event that enables bipolar mitosis for cancer cell lines harboring supernumerary centrosomes. We report herein the synthesis and SAR of 34...

  5. Extrahepatic synthesis of coagulation factor Ⅶ by colorectal cancer cells promotes tumor invasion and metastasis

    Institute of Scientific and Technical Information of China (English)

    TANG Jian-qiang; FAN Qing; WU Wen-han; JIA Zhi-chao; LI Hui; YANG Yin-mo; LIU Yu-cun; WAN Yuan-lian

    2010-01-01

    Background Blood coagulation factor Ⅶ (FⅦ) is physiologically synthesized in the liver and released into the blood. Binding of FⅦ to tissue factor (TF) is related to the metastatic potential of tumor cells, also a significant risk factor in the development of hepatic metastasis in patients with colorectal cancer (CRC). It has been found that some cancer cells can produce FⅦ extrahepatically. However, litte is known about FⅦ and CRC. We therefore hypothesized that CRC cells may synthese FⅦ, leading to tumor invasion and metastasis.Methods We detected the expression of FⅦ protein in 55 CRC specimens by immunohistochemical staining. The FⅦ mRNA in 45 of 55 CRC cases, 6 colon cancer cell lines and one hepatoma cell line was measured by real-time reverse transcription-PCR (RT-PCR). Transwell invasion assays were performed to evaluate the changes of cell migration and invasion of LoVo cancer cells in vitro. We further observed the likely effectors regulated by the TF/FⅦa complex Western blotting assay.Results Extrahepatic synthesis of FⅦ was detected in the cytoplasm of 32 (58.2%) CRC specimens byimmunohistochemistry, but not in normal mucosa. Liver metastasis (P=0.003) and TNM staging (P=0.005) were significantly correlated with FⅦ antigen expression. The positive ratios in stages Ⅰ, Ⅱ, Ⅲ and Ⅳ were 33.3%, 40.0%,52.4% and 87.5%, respectively. The expression of FⅦ mRNA in CRC with hepatic metastasis was significantly higher than CRC without hepatic metastasis (5.33±2.88 vs. 1.47±0.51, P=0.03). Ectopic FⅦa induced a slight increase (1.34-fold) in the number of migrating cells, which was inhibited by the specific TF antibody. The formation of TF/FⅦacomplex resulted in a marked increase in the expression of matrix metalloproteinases (MMP)-2 (3.5-fold) and MMP-9(4.7-fold) in a time-dependent and dose-dependent manner.Conclusions Extrahepatic synthesis of FⅦ by CRC cells may promote tumor invasion and metastasis. MMPs, as downstream

  6. Synthesis and characterization of jacalin-gold nanoparticles conjugates as specific markers for cancer cells.

    Science.gov (United States)

    Marangoni, Valeria S; Paino, Ieda M; Zucolotto, Valtencir

    2013-12-01

    New nanobiocomposites that combine nanoparticles and biomolecules have been shown very relevant for medical applications. Recently, cancer diagnostics and treatment have benefited from the development of nanobiocomposites, in which metallic or magnetic nanoparticles are conjugated with specific biomolecules for selective cell uptake. Despite recent advances in this area, the biomedical applications of these materials are still limited by the low efficiency of functionalization, low stability, among other factors. In this study, we report the synthesis of jacalin-conjugated gold nanoparticles, a nanoconjugate with potential application in medical areas, especially for cancer diagnosis. Jacalin is a lectin protein and it was employed due to its ability to recognize the Galβ1-3GalNAc disaccharide, which is highly expressed in tumor cells. Gold nanoparticles (AuNPs) were synthesized in the presence of generation 4 polyamidoamine dendrimer (PAMAM G4) and conjugated with fluorescein isothiocyanate (FITC)-labeled jacalin. The AuNPs/jacalin nanoconjugates were characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS) and vibrational spectroscopy (FTIR). We also performed an investigation using isothermal titration calorimetry (ITC) and fluorescence quenching measurements to understand the interactions occurring between the AuNPs and jacalin, which revealed that the nanoconjugate formation is driven by an entropic process with good affinity. Furthermore, in vitro tests revealed that the AuNPs/jacalin-FITC nanoconjugates exhibited higher affinity for leukemic K562 cells than for healthy mononuclear blood cells, which could be useful for biomedical applications, including cancer cells imaging.

  7. Immunotoxin targeting glypican-3 regresses liver cancer via dual inhibition of Wnt signalling and protein synthesis.

    Science.gov (United States)

    Gao, Wei; Tang, Zhewei; Zhang, Yi-Fan; Feng, Mingqian; Qian, Min; Dimitrov, Dimiter S; Ho, Mitchell

    2015-03-11

    Glypican-3 is a cell surface glycoprotein that associates with Wnt in liver cancer. We develop two antibodies targeting glypican-3, HN3 and YP7. The first antibody recognizes a functional epitope and inhibits Wnt signalling, whereas the second antibody recognizes a C-terminal epitope but does not inhibit Wnt signalling. Both are fused to a fragment of Pseudomonas exotoxin A (PE38) to create immunotoxins. Interestingly, the immunotoxin based on HN3 (HN3-PE38) has superior antitumor activity as compared with YP7 (YP7-PE38) both in vitro and in vivo. Intravenous administration of HN3-PE38 alone, or in combination with chemotherapy, induces regression of Hep3B and HepG2 liver tumour xenografts in mice. This study establishes glypican-3 as a promising candidate for immunotoxin-based liver cancer therapy. Our results demonstrate immunotoxin-induced tumour regression via dual mechanisms: inactivation of cancer signalling via the antibody and inhibition of protein synthesis via the toxin.

  8. The Experience of Caregivers Living with Cancer Patients: A Systematic Review and Meta-Synthesis

    Science.gov (United States)

    LeSeure, Peeranuch; Chongkham-ang, Supaporn

    2015-01-01

    The objectives of this meta-synthesis were to: (1) explore the experience of caregivers who were caring for cancer patients, including their perceptions and responses to the situation; and (2) describe the context and the phenomena relevant to the experience. Five databases were used: CINAHL, MEDLINE, Academic Search, Science Direct, and a Thai database known as the Thai Library Integrated System (ThaiLIS). Three sets of the context of the experience and the phenomena relevant to the experience were described. The contexts were (1) having a hard time dealing with emotional devastation; (2) knowing that the caregiving job was laborious; and (3) knowing that I was not alone. The phenomenon showed the progress of the caregivers’ thoughts and actions. A general phenomenon of the experience—balancing my emotion—applied to most of the caregivers; whereas, more specific phenomenon—keeping life as normal as possible and lifting life above the illness—were experienced by a lesser number of the caregivers. This review added a more thorough explanation of the issues involved in caregiving for cancer patients. A more comprehensive description of the experience of caregiving was described. The findings of this review can be used to guide clinical practice and policy formation in cancer patient care. PMID:26610573

  9. Facile Diversity-Oriented Synthesis of Polycyclic Pyridines and Their Cytotoxicity Effects in Human Cancer Cell Lines.

    Science.gov (United States)

    Goswami, Limi; Gogoi, Shyamalee; Gogoi, Junali; Boruah, Rajani K; Boruah, Romesh C; Gogoi, Pranjal

    2016-05-09

    A three-component cascade method has been developed for the direct synthesis of polysubstituted pyridines. This strategy provides a very convenient route to pyridines using a variety of β-bromo-α,β-unsaturated aldehydes, 1,3-diketones, and ammonium acetate without any additional catalyst or metal salt under mild conditions. A variety of β-ketoesters and 4-hydroxycoumarin were also used instead of 1,3-diketones for the diverse synthesis of polycyclic pyridines. One of the synthesized pyridines has been unambiguously established by a single crystal XRD study. All of the synthesized pyridine derivatives were evaluated for their antiproliferative properties in vitro against the human cancer cell lines HeLa, Me180, and ZR751. Compounds 4{4,1} and 4{2,4} showed significant cytotoxicity in the human breast cancer cell line ZR751 and cervical cancer cell line Me180, respectively, and a few other compounds were found to have moderate activities.

  10. Prostate cancer: towards the standardization and synthesis of morphology, genetics, and prognosis.

    Science.gov (United States)

    Berney, Dan; Cheng, Liang

    2012-01-01

    Prostate cancer research and diagnosis is undergoing a revolution in our understanding of the disease process and standardization of diagnostic criteria. Although great progress has been made, there remain many areas of uncertainty and debate. The revolution towards a synthesis of pathology with genetic changes and prognostic models is only just beginning. This supplement presents the opinions and findings of leading international experts in histopathology and prostate research dealing with subjects ranging from aetiology, basic anatomy and morphology to prognostic models, genetic changes and new drug treatments. We hope that this exciting and rapidly changing field will capture the imagination of both experienced and trainee pathologists to advance the field in both research and diagnosis.

  11. Green synthesis of gold nanoparticles for staining human cervical cancer cells and DNA binding assay.

    Science.gov (United States)

    De, Swati; Kundu, Rikta; Ghorai, Atanu; Mandal, Ranju Prasad; Ghosh, Utpal

    2014-11-01

    Gold nanoparticles have been functionalized by non-ionic surfactants (polysorbates) used in pharmaceutical formulations. This results in the formation of more well-dispersed gold nanoparticles (GNPs) than the GNPs formed in neat water. The synthesized GNPs show good temporal stability. The synthesis conditions are mild and environmentally benign. The GNPs can bind to ct-DNA and displace bound dye molecules. The DNA-binding assay is significant as it preliminarily indicated that DNA-GNP conjugates can be formed. Such conjugates are extremely promising for applications in nanobiotechnology. The GNPs can also stain the human cervical cancer (HeLa) cells over a wide concentration range while remaining non-cytotoxic, thus providing a non invasive cell staining method. This result is very promising as we observe staining of HeLa cells at very low GNP concentrations (1 μM) while the cell viability is retained even at 10-fold higher GNP concentrations.

  12. Adaptive Reprogramming of De Novo Pyrimidine Synthesis Is a Metabolic Vulnerability in Triple-Negative Breast Cancer.

    Science.gov (United States)

    Brown, Kristin K; Spinelli, Jessica B; Asara, John M; Toker, Alex

    2017-04-01

    Chemotherapy resistance is a major barrier to the treatment of triple-negative breast cancer (TNBC), and strategies to circumvent resistance are required. Using in vitro and in vivo metabolic profiling of TNBC cells, we show that an increase in the abundance of pyrimidine nucleotides occurs in response to chemotherapy exposure. Mechanistically, elevation of pyrimidine nucleotides induced by chemotherapy is dependent on increased activity of the de novo pyrimidine synthesis pathway. Pharmacologic inhibition of de novo pyrimidine synthesis sensitizes TNBC cells to genotoxic chemotherapy agents by exacerbating DNA damage. Moreover, combined treatment with doxorubicin and leflunomide, a clinically approved inhibitor of the de novo pyrimidine synthesis pathway, induces regression of TNBC xenografts. Thus, the increase in pyrimidine nucleotide levels observed following chemotherapy exposure represents a metabolic vulnerability that can be exploited to enhance the efficacy of chemotherapy for the treatment of TNBC.Significance: The prognosis for patients with TNBC with residual disease after chemotherapy is poor. We find that chemotherapy agents induce adaptive reprogramming of de novo pyrimidine synthesis and show that this response can be exploited pharmacologically, using clinically approved inhibitors of de novo pyrimidine synthesis, to sensitize TNBC cells to chemotherapy. Cancer Discov; 7(4); 391-9. ©2017 AACR.See related article by Mathur et al., p. 380This article is highlighted in the In This Issue feature, p. 339.

  13. Ovarian epithelial cancer: a role for PGE2-synthesis and signalling in malignant transformation and progression

    Directory of Open Access Journals (Sweden)

    Hedin Lars

    2006-11-01

    Full Text Available Abstract Background The involvement of the cyclooxygenases (COX, in particular COX-2, is well documented for many tumours, e.g. colon, breast and prostate cancer, by both experimental and clinical studies. There are epidemiological data from subjects using NSAIDs, and experimental evidence supporting the hypothesis of prostaglandins (PGs as regulators of tumourigenesis in the ovary. One of the end products of PG-synthesis, PGE2, regulates several key-processes, which are characteristic for tumour growth, e.g. angiogenesis, proliferation and apoptosisis. The present study investigated the pathway for PGE2 – synthesis and signalling in ovarian tumourigenesis by analysing specimen from normal ovaries (n = 18, benign (B (n = 8, borderline type (BL (n = 6 and malignant tumours (AC (n = 22. The expression and cell-specific localization of COX-1, COX-2, microsomal prostaglandin E synthase-1 (mPGES-1 and two of the receptors for PGE2, EP1 and EP2, were examined by immunoblotting (IB and immunohistochemistry (IHC. Results The results are in line with earlier studies demonstrating an increase of COX-2 in AC compared to the normal ovary, B and BL tumours. Increased expressions were also observed for COX-1, mPGES-1 and EP-1 which all were significantly (p 1 was increased in stage III while no significant alterations were demonstrated for COX-1, mPGES-1 or EP2 for stage. IHC revealed staining of the tumour cells, but also increase of COX-1, COX-2, mPGES-1 and EP1–2 in the stromal compartment of AC (grades: moderately-, poorly- and undifferentiated. This observation suggests interactions between tumour cells and stromal cells (fibroblasts, immune cells, e.g. paracrine signalling mediated by growth factors, cytokines and possibly PGs. Conclusion The increases of COX-1, COX-2, mPGES-1 and EP1–2 in epithelial ovarian cancer, supports the hypothesis that PGE2-synthesis and signalling are of importance for malignant transformation and progression. The

  14. Tracer-tracer relations as a tool for research on polar ozone loss

    Energy Technology Data Exchange (ETDEWEB)

    Mueller, Rolf

    2010-07-01

    The report includes the following chapters: (1) Introduction: ozone in the atmosphere, anthropogenic influence on the ozone layer, polar stratospheric ozone loss; (2) Tracer-tracer relations in the stratosphere: tracer-tracer relations as a tool in atmospheric research; impact of cosmic-ray-induced heterogeneous chemistry on polar ozone; (3) quantifying polar ozone loss from ozone-tracer relations: principles of tracer-tracer correlation techniques; reference ozone-tracer relations in the early polar vortex; impact of mixing on ozone-tracer relations in the polar vortex; impact of mesospheric intrusions on ozone-tracer relations in the stratospheric polar vortex calculation of chemical ozone loss in the arctic in March 2003 based on ILAS-II measurements; (4) epilogue.

  15. Prostate cancer and supportive care: a systematic review and qualitative synthesis of men's experiences and unmet needs.

    Science.gov (United States)

    King, A J L; Evans, M; Moore, T H M; Paterson, C; Sharp, D; Persad, R; Huntley, A L

    2015-09-01

    Prostate cancer is the second most common cancer in men worldwide, accounting for an estimated 1.1 million new cases diagnosed in 2012 (www.globocan.iarc.fr). Currently, there is a lack of specific guidance on supportive care for men with prostate cancer. This article describes a qualitative systematic review and synthesis examining men's experience of and need for supportive care. Seven databases were searched; 20 journal articles were identified and critically appraised. A thematic synthesis was conducted in which descriptive themes were drawn out of the data. These were peer support, support from partner, online support, cancer specialist nurse support, self-care, communication with health professionals, unmet needs (emotional support, information needs, support for treatment-induced side effects of incontinence and erectile dysfunction) and men's suggestions for improved delivery of supportive care. This was followed by the development of overarching analytic themes which were: uncertainty, reframing, and the timing of receiving treatment, information and support. Our results show that the most valued form of support men experienced following diagnosis was one-to-one peer support and support from partners. This review highlights the need for improved access to cancer specialist nurses throughout the care pathway, individually tailored supportive care and psychosexual support for treatment side effects.

  16. Synthesis, saccharide-binding and anti-cancer cell proliferation properties of arylboronic acid derivatives of indoquinolines.

    Science.gov (United States)

    Meng, Junxiu; Yu, Shaoqing; Wan, Shengbiao; Ren, Sumei; Jiang, Tao

    2011-11-01

    A facile synthesis of a series of saccharide-binding arylboronic acid derivatives of indoloquinoline was described. The key synthetic steps were polyphosphoric acid-mediated cyclization, chlorinative aromatization, and amidation. Mass spectrometry experiments revealed these synthetic arylboronic acid derivatives of indoquinolines could bind to biologically important carbohydrates (sialic acid, fucose, glucose, and galactose) by forming boronate di-esters in alkaline aqueous solution. Most of the arylboronic acid derivatives of indoquinolines inhibited human breast cancer cell (MDA-231) proliferation at a concentration of 5 μm, whereas the compound 17 exhibited highest percentages (76.74%) of the cancer cell proliferation inhibition.

  17. Tracer diffusion inside fibrinogen layers

    Science.gov (United States)

    Cieśla, Michał; Gudowska-Nowak, Ewa; Sagués, Francesc; Sokolov, Igor M.

    2014-01-01

    We investigate the obstructed motion of tracer (test) particles in crowded environments by carrying simulations of two-dimensional Gaussian random walk in model fibrinogen monolayers of different orientational ordering. The fibrinogen molecules are significantly anisotropic and therefore they can form structures where orientational ordering, similar to the one observed in nematic liquid crystals, appears. The work focuses on the dependence between level of the orientational order (degree of environmental crowding) of fibrinogen molecules inside a layer and non-Fickian character of the diffusion process of spherical tracer particles moving within the domain. It is shown that in general particles motion is subdiffusive and strongly anisotropic, and its characteristic features significantly change with the orientational order parameter, concentration of fibrinogens, and radius of a diffusing probe.

  18. Tracer diffusion inside fibrinogen layers

    CERN Document Server

    Cieśla, Michał; Sagués, Francesc; Sokolov, Igor M

    2013-01-01

    We investigate the motion of tracer (test) particles in crowded environments by carrying simulations of two-dimensional Gaussian random walk in model fibrinogen monolayers of different orientational ordering. The fibrinogen molecules are significantly anisotropic and therefore they can form structures where orientational ordering, similar to the one observed in nematic liquid crystals, appears. The work focuses on the dependence between level of the orientational order (degree of environmental crowding) of fibrinogen molecules inside a layer and non-Fickian character of the diffusion process of spherical tracer particles moving within the domain. It is shown that in general particles motion is subdiffusive and strongly anisotropic, and its characteristic features significantly change with the orientational order parameter, concentration of fibrinogens and radius of a diffusing probe.

  19. Green chemistry approach for the synthesis and stabilization of biocompatible gold nanoparticles and their potential applications in cancer therapy.

    Science.gov (United States)

    Mukherjee, Sudip; Sushma, V; Patra, Sujata; Barui, Ayan Kumar; Bhadra, Manika Pal; Sreedhar, Bojja; Patra, Chitta Ranjan

    2012-11-16

    The biological approach to synthesis of AuNPs is eco-friendly and an ideal method to develop environmentally sustainable nanoparticles alternative to existing methods. We have developed a simple, fast, clean, efficient, low-cost and eco-friendly single-step green chemistry approach for the synthesis of biocompatible gold nanoparticles (AuNPs) from chloroauric acid (HAuCl(4)) using a water extract of Eclipta Alba leaves at room temperature. The AuNPs using Eclipta extract have been formed in very short time, even in less than 10 min. The as-synthesized AuNPs were thoroughly characterized by several physico-chemical techniques. The in vitro stability of as-synthesized AuNPs was studied in different buffer solutions. A plausible mechanism for the synthesis of AuNPs by Eclipta extract has been discussed. The biocompatibility of AuNPs was observed by in vitro cell culture assays. Finally, we have designed and developed a AuNPs-based drug delivery system (DDS) (Au-DOX) containing doxorubicin (DOX), a FDA approved anticancer drug. Administration of this DDS to breast cancer cells (MCF-7 and MDA-MB-231) shows significant inhibition of breast cancer cell proliferation compared to pristine doxorubicin. Therefore we strongly believe that the use of Eclipta Alba offers large-scale production of biocompatible AuNPs that can be used as a delivery vehicle for the treatment of cancer diseases.

  20. Green chemistry approach for the synthesis and stabilization of biocompatible gold nanoparticles and their potential applications in cancer therapy

    Science.gov (United States)

    Mukherjee, Sudip; Sushma, V.; Patra, Sujata; Barui, Ayan Kumar; Pal Bhadra, Manika; Sreedhar, Bojja; Ranjan Patra, Chitta

    2012-11-01

    The biological approach to synthesis of AuNPs is eco-friendly and an ideal method to develop environmentally sustainable nanoparticles alternative to existing methods. We have developed a simple, fast, clean, efficient, low-cost and eco-friendly single-step green chemistry approach for the synthesis of biocompatible gold nanoparticles (AuNPs) from chloroauric acid (HAuCl4) using a water extract of Eclipta Alba leaves at room temperature. The AuNPs using Eclipta extract have been formed in very short time, even in less than 10 min. The as-synthesized AuNPs were thoroughly characterized by several physico-chemical techniques. The in vitro stability of as-synthesized AuNPs was studied in different buffer solutions. A plausible mechanism for the synthesis of AuNPs by Eclipta extract has been discussed. The biocompatibility of AuNPs was observed by in vitro cell culture assays. Finally, we have designed and developed a AuNPs-based drug delivery system (DDS) (Au-DOX) containing doxorubicin (DOX), a FDA approved anticancer drug. Administration of this DDS to breast cancer cells (MCF-7 and MDA-MB-231) shows significant inhibition of breast cancer cell proliferation compared to pristine doxorubicin. Therefore we strongly believe that the use of Eclipta Alba offers large-scale production of biocompatible AuNPs that can be used as a delivery vehicle for the treatment of cancer diseases.

  1. A novel electrophilic synthesis and evaluation of medium specific radioactivity (1R,2S)-4-[{sup 18}F]fluorometaraminol, a tracer for the assessment of cardiac sympathetic nerve integrity with PET

    Energy Technology Data Exchange (ETDEWEB)

    Eskola, Olli E-mail: olesko@utu.fi; Groenroos, Tove; Bergman, Joergen; Haaparanta, Merja; Marjamaeki, Paeivi; Lehikoinen, Pertti; Forsback, Sarita; Langer, Oliver; Hinnen, Francoise; Dolle, Frederic; Halldin, Christer; Solin, Olof

    2004-01-01

    (1R,2S)-4-[{sup 18}F]fluorometaraminol (4-[{sup 18}F]FMR), a tracer for cardiac sympathetic innervation, was synthesized by electrophilic aromatic substitution. A trimethylstannyl precursor, protected with tert-butoxycarbonyl protecting groups, was radiofluorinated with high specific radioactivity [{sup 18}F]F{sub 2}. Specific radioactivity of 4-[{sup 18}F]FMR, in average 11.8 {+-}3.3 GBq/{mu}mol, was improved 40-800-fold in comparison to the previous electrophilic fluorinations. The biodistribution of 4-[{sup 18}F]FMR in rat was in accordance with the known distribution of sympathetic innervation. 4-[{sup 18}F]FMR showed no metabolic degradation in left ventricle of rat heart, where the uptake was high, rapid and specific.

  2. Lipin-1 regulation of phospholipid synthesis maintains endoplasmic reticulum homeostasis and is critical for triple-negative breast cancer cell survival.

    Science.gov (United States)

    He, Jingquan; Zhang, Feng; Tay, Li Wei Rachel; Boroda, Salome; Nian, Weiqi; Levental, Kandice R; Levental, Ilya; Harris, Thurl E; Chang, Jeffrey T; Du, Guangwei

    2017-03-27

    Cancer cells reprogram their metabolism to increase the synthesis of macromolecules for rapid proliferation. Compared to fatty acids, much less is known about the synthesis of phospholipids, which is essential for membrane biogenesis in cancer cells. We found that LPIN1, which encodes lipin-1, a phosphatidic acid phosphatase (PAP) controlling the rate-limiting step in the phospholipid synthesis pathway, is highly up-regulated in basal-like triple-negative breast cancer (TNBC). Moreover, high LPIN1 expression correlates with the poor prognosis of these patients. Knockdown of LPIN1 increases apoptosis in basal-like TNBC cell lines, whereas it has minimal or less effect on normal human mammary gland epithelial cells (HMECs) and estrogen receptor-positive breast cancer cell lines. Fatty acid incorporation and lipidomics analyses showed that LPIN1 knockdown blocks phospholipid synthesis and changes membrane lipid compositions that ultimately induce the activation of 1 of the 3 branches of unfolded protein responses, the inositol-requiring enzyme-1α pathway. We also show for the first time, to our knowledge, that lipin-1 knockdown significantly inhibits tumor growth in vivo using an orthotopic xenograft breast mouse model. Our results suggest that lipin-1 is a potential target for cancer therapy.-He, J., Zhang, F., Tay, L. W. R., Boroda, S., Nian, W., Levental, K. R., Levental, I., Harris, T. E., Chang, J. T., Du, G. Lipin-1 regulation of phospholipid synthesis maintains endoplasmic reticulum homeostasis and is critical for triple-negative breast cancer cell survival.

  3. Comparison of different tracer methods in detecting sentinel lymph nodes in gastric cancer%不同示踪法在胃癌前哨淋巴结检测中的应用比较

    Institute of Scientific and Technical Information of China (English)

    程黎阳; 谢正勇; 戴观荣; 赵为国; 王弘; 周宏峰

    2010-01-01

    Objective To explore the optimum sentinel lymph node (SLN) mapping method in gastric cancer. Methods The clinical data of 59 patients who were confirmed with gastric cancer at Guangzhou General Hospital of Guangzhou Military Command from January 2004 to August 2008 were retrospectively analysed. Patent blue V dye was used in 20 patients (group A), technetium-99m sulfur colloid was used in 20 patients (group B),and a combination of patent blue V dye and technetium-99m sulfur colloid were used in 19 patients (group C).The number of SLNs detected, and accuracy and false-negative rate of SLNs in diagnosing regional lymph node metastasis were analysed by t test and chi-square test. Results The numbers of SLNs detected in groups A, B and C were 38 (1.9 per case), 31 (1.6 per case) and 56 (2.9 per case), respectively. In group C, 46 SLNs were screened out by patent blue V dye and technetium-99m sulfur colloid simultaneously, six SLNs were only detected by patent blue V dye and four only by technetium-99m sulfur colloid. There was a significant difference in the number of SLNs detected among the three groups (t = 4.35, P < 0. 05 ). The number of SLNs detected in group C was significantly greater than that in groups A and B (t = 4. 21, 3. 54, P < 0.05 ). The accuracy and false-negative rate of SLNs in diagnosing regional lymph node metastasis were 95% (19/20) and 5% (1/20) in group A, 90% (18/20) and 10% (2/20) in group B, and 100% (19/19) and 0 in group C. The accuracy was significantly higher (x2 = 163.01, P < 0.05) and the false-negative rate was significantly lower in group C compared with those in groups A and B (x2 = 170. 14, P < 0. 05). Conclusion A combination of dye and radioactive tracer is a favorable method for detecting SLNs in gastric cancer.%目的 探讨理想的胃癌前哨淋巴结(SLN)检测方法.方法 前瞻性分析2004年1月至2008年8月广州军区广州总医院确诊的59例胃癌患者的临床资料,按随机数字表

  4. Green synthesis of anisotropic gold nanoparticles for photothermal therapy of cancer.

    Science.gov (United States)

    Fazal, Sajid; Jayasree, Aswathy; Sasidharan, Sisini; Koyakutty, Manzoor; Nair, Shantikumar V; Menon, Deepthy

    2014-06-11

    Nanoparticles of varying composition, size, shape, and architecture have been explored for use as photothermal agents in the field of cancer nanomedicine. Among them, gold nanoparticles provide a simple platform for thermal ablation owing to its biocompatibility in vivo. However, the synthesis of such gold nanoparticles exhibiting suitable properties for photothermal activity involves cumbersome routes using toxic chemicals as capping agents, which can cause concerns in vivo. Herein, gold nanoparticles, synthesized using green chemistry routes possessing near-infrared (NIR) absorbance facilitating photothermal therapy, would be a viable alternative. In this study, anisotropic gold nanoparticles were synthesized using an aqueous route with cocoa extract which served both as a reducing and stabilizing agent. The as-prepared gold nanoparticles were subjected to density gradient centrifugation to maximize its NIR absorption in the wavelength range of 800-1000 nm. The particles also showed good biocompatibility when tested in vitro using A431, MDA-MB231, L929, and NIH-3T3 cell lines up to concentrations of 200 μg/mL. Cell death induced in epidermoid carcinoma A431 cells upon irradiation with a femtosecond laser at 800 nm at a low power density of 6 W/cm(2) proved the suitability of green synthesized NIR absorbing anisotropic gold nanoparticles for photothermal ablation of cancer cells. These gold nanoparticles also showed good X-ray contrast when tested using computed tomography (CT), proving their feasibility for use as a contrast agent as well. This is the first report on green synthesized anisotropic and cytocompatible gold nanoparticles without any capping agents and their suitability for photothermal therapy.

  5. Androgen synthesis inhibitors in the treatment of castration-resistant prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Mark N Stein; Neal Patel; Alexander Bershadskiy; Alisa Sokoloff; Eric A Singer

    2014-01-01

    Suppression of gonadal testosterone synthesis represents the standard ifrst line therapy for treatment of metastatic prostate cancer. However, in the majority of patients who develop castration-resistant prostate cancer (CRPC), it is possible to detect persistent activation of the androgen receptor (AR) through androgens produced in the adrenal gland or within the tumor itself. Abiraterone acetate was developed as an irreversible inhibitor of the dual functional cytochrome P450 enzyme CYP17 with activity as a 17α-hydroxylase and 17,20-lyase. CYP17 is necessary for production of nongonadal androgens from cholesterol. Regulatory approval of abiraterone in 2011, based on a phase III trial showing a signiifcant improvement in overall survival (OS) with abiraterone and prednisone versus prednisone, represented proof of principle that targeting AR is essential for improving outcomes in men with CRPC. Inhibition of 17α-hydroxylase by abiraterone results in accumulation of upstream mineralocorticoids due to loss of cortisol-mediated suppression of pituitary adrenocorticotropic hormone (ACTH), providing a rationale for development of CYP17 inhibitors with increased speciifcity for 17,20-lyase (orteronel, galeterone and VT-464) that can potentially be administered without exogenous corticosteroids. In this article, we review the development of abiraterone and other CYP17 inhibitors;recent studies with abiraterone that inform our understanding of clinical parameters such as drug effects on quality-of-life, potential early predictors of response, and optimal sequencing of abiraterone with respect to other agents;and results of translational studies providing insights into resistance mechanisms to CYP17 inhibitors leading to clinical trials with drug combinations designed to prolong abiraterone beneift or restore abiraterone activity.

  6. Tracer tests in geothermal resource management

    Directory of Open Access Journals (Sweden)

    Axelsson G.

    2013-05-01

    Full Text Available Geothermal reinjection involves injecting energy-depleted fluid back into geothermal systems, providing an effective mode of waste-water disposal as well as supplementary fluid recharge. Cooling of production boreholes is one of the main disadvantages associated with reinjection, however. Tracer testing is an important tool for reinjection studies because tracer tests actually have a predictive power since tracer transport is orders of magnitude faster than cold-front advancement around reinjection boreholes. A simple and efficient method of tracer test interpretation, assuming specific flow channels connecting reinjection and production boreholes, is available. It simulates tracer return profiles and estimates properties of the flow channels, which are consequently used for predicting the production borehole cooling. Numerous examples are available worldwide on the successful application of tracer tests in geothermal management, many involving the application of this interpretation technique. Tracer tests are also used for general subsurface hydrological studies in geothermal systems and for flow rate measurements in two-phase geothermal pipelines. The tracers most commonly used in geothermal applications are fluorescent dyes, chemical substances and radioactive isotopes. New temperature-resistant tracers have also been introduced and high-tech tracers are being considered.

  7. Dealing with cancer: a meta-synthesis of patients’ and relatives’ experiences of participating in psychosocial interventions

    DEFF Research Database (Denmark)

    Hoeck, Bente; Ledderer, Loni; Hansen, Helle Ploug

    2017-01-01

    The aim was to synthesise patients’ and relatives’ experiences of participating in a psychosocial intervention related to having cancer. The study was a meta-synthesis inspired by Noblit & Hare’s ‘meta-ethnography’ approach. We systematically searched six databases and included 33 studies...... symbolising the participants’ core experiences were identified: 1) Emotional relief and a sense of well-being, 2) normalisation of experiences and a sense of control, 3) shared experience and a sense of community, 4) a safe place and 5) transformation and adaptability. The findings indicated that psychosocial...... interventions were used to try to deal with the changes in the human conditions caused by cancer. Sharing their experiences and forming social relationships helped the participants adapt to cancer. An existential perspective may provide a nuanced understanding of patients’ and relatives’ experiences...

  8. Synthesis and cytotoxic activity of certain benzothiazole derivatives against human MCF-7 cancer cell line.

    Science.gov (United States)

    Mohamed, Lamia W; Taher, Azza T; Rady, Ghada S; Ali, Mamdouh M; Mahmoud, Abeer E

    2016-10-04

    A new series of benzothiazole has been synthesized as cytotoxic agents. The new derivatives were tested for their cytotoxic activity toward the human breast cancer MCF-7 cell line against cisplatin as the reference drug. Many derivatives revealed good cytotoxic effect, whereas four of them, 4, 5c, 5d, and 6b, were more potent than cisplatin, with IC50 values being 8.64, 7.39, 7.56, and 5.15 μm compared to 13.33 μm of cisplatin. The four derivatives' cytotoxic activity was accompanied by regulating free radicals production, by increasing the activity of superoxide dismutase and depletion of intracellular reduced glutathione, catalase, and glutathione peroxidase activities, accordingly, the high production of hydrogen peroxide, nitric oxide, and other free radicals causing tumor cell death as monitored by reduction in the synthesis of protein and nucleic acids. Most of the tested compounds showed potent to moderate growth inhibitory activity; in particular, compound 6b exhibited the highest activity suggesting it is a lead compound in cytotoxic activity.

  9. Design, synthesis and validation of integrin {alpha}{sub 2}{beta}{sub 1}-targeted probe for microPET imaging of prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Chiun-Wei; Li, Zibo; Cai, Hancheng; Chen, Kai; Shahinian, Tony; Conti, Peter S. [University of Southern California, Department of Radiology, Los Angeles, CA (United States)

    2011-07-15

    The ability of PET to aid in the diagnosis and management of recurrent and/or disseminated metastatic prostate cancer may be enhanced by the development of novel prognostic imaging probes. Accumulating experimental evidence indicates that overexpression of integrin {alpha}{sub 2}{beta}{sub 1} may correlate with progression in human prostate cancer. In this study, {sup 64}Cu-labeled integrin {alpha}{sub 2}{beta}{sub 1}-targeted PET probes were designed and evaluated for the imaging of prostate cancer. DGEA peptides conjugated with a bifunctional chelator (BFC) were developed to image integrin {alpha}{sub 2}{beta}{sub 1} expression with PET in a subcutaneous PC-3 xenograft model. The microPET images were reconstructed by a two-dimensional ordered subsets expectation maximum algorithm. The average radioactivity accumulation within a tumor or an organ was quantified from the multiple region of interest volumes. The PET tracer demonstrated prominent tumor uptake in the PC-3 xenograft (integrin {alpha}{sub 2}{beta}{sub 1}-positive). The receptor specificity was confirmed in a blocking experiment. Moreover, the low tracer uptake in a CWR-22 tumor model (negative control) further confirmed the receptor specificity. The sarcophagine-conjugated DGEA peptide allows noninvasive imaging of tumor-associated {alpha}{sub 2}{beta}{sub 1} expression, which may be a useful PET probe for evaluating the metastatic potential of prostate cancer. (orig.)

  10. Tracer tests in geothermal resource management

    OpenAIRE

    Axelsson G.

    2013-01-01

    Geothermal reinjection involves injecting energy-depleted fluid back into geothermal systems, providing an effective mode of waste-water disposal as well as supplementary fluid recharge. Cooling of production boreholes is one of the main disadvantages associated with reinjection, however. Tracer testing is an important tool for reinjection studies because tracer tests actually have a predictive power since tracer transport is orders of magnitude faster than cold-front advancement around reinj...

  11. Tracer-Test Planning Using the Efficient Hydrologic Tracer-Test Design (Ehtd) Program (2003)

    Science.gov (United States)

    Hydrological tracer testing is the most reliable diagnostic technique available for establishing flow trajectories and hydrologic connections and for determining basic hydraulic and geometric parameters necessary for establishing operative solute-transport processes. Tracer-test ...

  12. RGD-based PET tracers for imaging receptor integrin αv β3 expression.

    Science.gov (United States)

    Cai, Hancheng; Conti, Peter S

    2013-05-15

    Positron emission tomography (PET) imaging of receptor integrin αv β3 expression may play a key role in the early detection of cancer and cardiovascular diseases, monitoring disease progression, evaluating therapeutic response, and aiding anti-angiogenic drugs discovery and development. The last decade has seen the development of new PET tracers for in vivo imaging of integrin αv β3 expression along with advances in PET chemistry. In this review, we will focus on the radiochemistry development of PET tracers based on arginine-glycine-aspartic acid (RGD) peptide, present an overview of general strategies for preparing RGD-based PET tracers, and review the recent advances in preparations of (18) F-labeled, (64) Cu-labeled, and (68) Ga-labeled RGD tracers, RGD-based PET multivalent probes, and RGD-based PET multimodality probes for imaging receptor integrin αv β3 expression.

  13. Tracers for Characterizing Enhanced Geothermal Systems

    Energy Technology Data Exchange (ETDEWEB)

    Karen Wright; George Redden; Carl D. Palmer; Harry Rollins; Mark Stone; Mason Harrup; Laurence C. Hull

    2010-02-01

    Information about the times of thermal breakthrough and subsequent rates of thermal drawdown in enhanced geothermal systems (EGS) is necessary for reservoir management, designing fracture stimulation and well drilling programs, and forecasting economic return. Thermal breakthrough in heterogeneous porous media can be estimated using conservative tracers and assumptions about heat transfer rates; however, tracers that undergo temperature-dependent changes can provide more detailed information about the thermal profile along the flow path through the reservoir. To be effectively applied, the thermal reaction rates of such temperature sensitive traces must be well characterized for the range of conditions that exist in geothermal systems. Reactive tracers proposed in the literature include benzoic and carboxylic acids (Adams) and organic esters and amides (Robinson et al.); however, the practical temperature range over which these tracers can be applied (100-275°C) is somewhat limited. Further, for organic esters and amides, little is known about their sorption to the reservoir matrix and how such reactions impact data interpretation. Another approach involves tracers where the reference condition is internal to the tracer itself. Two examples are: 1) racemization of polymeric amino acids, and 2) mineral thermoluminescence. In these cases internal ratios of states are measured rather than extents of degradation and mass loss. Racemization of poly-L-lactic acid (for example) is temperature sensitive and therefore can be used as a temperature-recording tracer depending on the rates of racemization and stability of the amino acids. Heat-induced quenching of thermoluminescence of pre-irradiated LiF can also be used. To protect the tracers from alterations (extraneous reactions, dissolution) in geothermal environments we are encapsulating the tracers in core-shell colloidal structures that will subsequently be tested for their ability to be transported and to protect the

  14. Type I Collagen Synthesis Marker Procollagen I N-Terminal Peptide (PINP) in Prostate Cancer Patients Undergoing Intermittent Androgen Suppression

    Energy Technology Data Exchange (ETDEWEB)

    Hamilton, Gerhard, E-mail: gerhard.hamilton@toc.lbg.ac.at; Olszewski-Hamilton, Ulrike [Ludwig Boltzmann Cluster of Translational of Oncology, Nussdorfer Strasse 64, Vienna A-1090 (Austria); Theyer, Gerhard [Hospital Kittsee, Kittsee A-2421, Burgenland (Austria)

    2011-09-15

    Intermittent androgen suppression (IAS) therapy for prostate cancer patients attempts to maintain the hormone dependence of the tumor cells by cycles alternating between androgen suppression (AS) and treatment cessation till a certain prostate-specific antigen (PSA) threshold is reached. Side effects are expected to be reduced, compared to standard continuous androgen suppression (CAS) therapy. The present study examined the effect of IAS on bone metabolism by determinations of serum procollagen I N-terminal peptide (PINP), a biochemical marker of collagen synthesis. A total of 105 treatment cycles of 58 patients with prostate cancer stages ≥pT2 was studied assessing testosterone, PSA and PINP levels at monthly intervals. During phases of AS lasting for up to nine months PSA levels were reversibly reduced, indicating apoptotic regression of the prostatic tumors. Within the first cycle PINP increased at the end of the AS period and peaked in the treatment cessation phase. During the following two cycles a similar pattern was observed for PINP, except a break in collagen synthesis as indicated by low PINP levels in the first months off treatment. Therefore, measurements of the serum PINP concentration indicated increased bone matrix synthesis in response to >6 months of AS, which uninterruptedly continued into the first treatment cessation phase, with a break into each of the following two pauses. In summary, synthesis of bone matrix collagen increases while degradation decreases during off-treatment phases in patients undergoing IAS. Although a direct relationship between bone matrix turnover and risk of fractures is difficult to establish, IAS for treatment of biochemical progression of prostate tumors is expected to reduce osteoporosis in elderly men often at high risk for bone fractures representing a highly suitable patient population for this kind of therapy.

  15. Bacteriophages as surface and ground water tracers

    Directory of Open Access Journals (Sweden)

    P. Rossi

    1998-01-01

    Full Text Available Bacteriophages are increasingly used as tracers for quantitative analysis in both hydrology and hydrogeology. The biological particles are neither toxic nor pathogenic for other living organisms as they penetrate only a specific bacterial host. They have many advantages over classical fluorescent tracers and offer the additional possibility of multi-point injection for tracer tests. Several years of research make them suitable for quantitative transport analysis and flow boundary delineation in both surface and ground waters, including karst, fractured and porous media aquifers. This article presents the effective application of bacteriophages based on their use in differing Swiss hydrological environments and compares their behaviour to conventional coloured dye or salt-type tracers. In surface water and karst aquifers, bacteriophages travel at about the same speed as the typically referenced fluorescent tracers (uranine, sulphurhodamine G extra. In aquifers of interstitial porosity, however, they appear to migrate more rapidly than fluorescent tracers, albeit with a significant reduction in their numbers within the porous media. This faster travel time implies that a modified rationale is needed for defining some ground water protection area boundaries. Further developments of other bacteriophages and their documentation as tracer methods should result in an accurate and efficient tracer tool that will be a proven alternative to conventional fluorescent dyes.

  16. Bacteriophages as surface and ground water tracers

    Science.gov (United States)

    Rossi, P.; Dörfliger, N.; Kennedy, K.; Müller, I.; Aragno, M.

    Bacteriophages are increasingly used as tracers for quantitative analysis in both hydrology and hydrogeology. The biological particles are neither toxic nor pathogenic for other living organisms as they penetrate only a specific bacterial host. They have many advantages over classical fluorescent tracers and offer the additional possibility of multi-point injection for tracer tests. Several years of research make them suitable for quantitative transport analysis and flow boundary delineation in both surface and ground waters, including karst, fractured and porous media aquifers. This article presents the effective application of bacteriophages based on their use in differing Swiss hydrological environments and compares their behaviour to conventional coloured dye or salt-type tracers. In surface water and karst aquifers, bacteriophages travel at about the same speed as the typically referenced fluorescent tracers (uranine, sulphurhodamine G extra). In aquifers of interstitial porosity, however, they appear to migrate more rapidly than fluorescent tracers, albeit with a significant reduction in their numbers within the porous media. This faster travel time implies that a modified rationale is needed for defining some ground water protection area boundaries. Further developments of other bacteriophages and their documentation as tracer methods should result in an accurate and efficient tracer tool that will be a proven alternative to conventional fluorescent dyes.

  17. The Accurate Particle Tracer Code

    CERN Document Server

    Wang, Yulei; Qin, Hong; Yu, Zhi

    2016-01-01

    The Accurate Particle Tracer (APT) code is designed for large-scale particle simulations on dynamical systems. Based on a large variety of advanced geometric algorithms, APT possesses long-term numerical accuracy and stability, which are critical for solving multi-scale and non-linear problems. Under the well-designed integrated and modularized framework, APT serves as a universal platform for researchers from different fields, such as plasma physics, accelerator physics, space science, fusion energy research, computational mathematics, software engineering, and high-performance computation. The APT code consists of seven main modules, including the I/O module, the initialization module, the particle pusher module, the parallelization module, the field configuration module, the external force-field module, and the extendible module. The I/O module, supported by Lua and Hdf5 projects, provides a user-friendly interface for both numerical simulation and data analysis. A series of new geometric numerical methods...

  18. Effect of tracer buoyancy on tracer experiments conducted in fractured crystalline bedrock

    Science.gov (United States)

    Becker, Matthew W.

    2003-02-01

    Tracer buoyancy has been shown to influence breakthrough from two-well tracer experiments conducted in porous media. Two-well tracer experiments are presented from fractured crystalline bedrock, in which the specific gravity of the tracer injectate varied from 1.0002 to 1.0133. Under the forced hydraulic conditions imposed, no difference in breakthrough was noted for the three experiments. These results show that even relatively dense tracer injectate solutions may have an insignificant effect on breakthrough when imposed gradients are sufficiently large.

  19. The Art of Tomographic Tracer Tests

    Science.gov (United States)

    Cirpka, O. A.; Leven, C.; Doro, K. O.; Sanchez-Leon, E. E.

    2015-12-01

    In tracer tomography several tracer tests are performed within an aquifer and breakthrough curves are observed at multiple observation points. In the analysis, hydraulic conductivity is estimated as spatially variable, 3-D field subject to some smoothness constraint. Coupled flow and transport models using this conductivity fields are requested to meet observed tracer data. The approach can be combined with hydraulic tomography.We have performed hydraulic-tomography and tracer-tomography tests using heat and fluorescein as tracers at a field site close to Tübingen, Germany. The aquifer consists of 8-9m alluvials sands and gravels overlain by 1-2m alluvial fines. The hydraulic setup consists of a forced flow field between an injection/extraction well couple, embedded in the forced flow field of another well couple. By turning injection to extraction wells, and vice versa, two different flow fields were considered. Injection wells were separated into several sections by packers, and water was injected into each section proportional to its transmissivity. The water injected into one of the sections contained the tracer. Multi-level observation wells were equiped with thermometers (for heat-tracer tests), on-line fluoremeters (for teh dye tracers), and pressure transducers. Processing of the breakthrough curves included data cleaning, non-parametric deconvolution, and calculation of temperal moments of the estimated transfer functions.The joint inversion of hydraulic-head measurements and temporal moments of heat-tracer transfer functions was done by the quasi-linear geostatistical approach on a computing cluster. As alternative, we directly invert the time series (without temporal moments) by Ensemble-Kalman filtering.The high diffusion coefficient of temperature diminishes the penetration of the heat-tracer into the aquifer, which can partially be compensated by reverting the flow field and repeating the tracer tests. In tests with fluorscent tracers the signal

  20. Discovery of MK-3168: A PET Tracer for Imaging Brain Fatty Acid Amide Hydrolase.

    Science.gov (United States)

    Liu, Ping; Hamill, Terence G; Chioda, Marc; Chobanian, Harry; Fung, Selena; Guo, Yan; Chang, Linda; Bakshi, Raman; Hong, Qingmei; Dellureficio, James; Lin, Linus S; Abbadie, Catherine; Alexander, Jessica; Jin, Hong; Mandala, Suzanne; Shiao, Lin-Lin; Li, Wenping; Sanabria, Sandra; Williams, David; Zeng, Zhizhen; Hajdu, Richard; Jochnowitz, Nina; Rosenbach, Mark; Karanam, Bindhu; Madeira, Maria; Salituro, Gino; Powell, Joyce; Xu, Ling; Terebetski, Jenna L; Leone, Joseph F; Miller, Patricia; Cook, Jacquelynn; Holahan, Marie; Joshi, Aniket; O'Malley, Stacey; Purcell, Mona; Posavec, Diane; Chen, Tsing-Bau; Riffel, Kerry; Williams, Mangay; Hargreaves, Richard; Sullivan, Kathleen A; Nargund, Ravi P; DeVita, Robert J

    2013-06-13

    We report herein the discovery of a fatty acid amide hydrolase (FAAH) positron emission tomography (PET) tracer. Starting from a pyrazole lead, medicinal chemistry efforts directed toward reducing lipophilicity led to the synthesis of a series of imidazole analogues. Compound 6 was chosen for further profiling due to its appropriate physical chemical properties and excellent FAAH inhibition potency across species. [(11)C]-6 (MK-3168) exhibited good brain uptake and FAAH-specific signal in rhesus monkeys and is a suitable PET tracer for imaging FAAH in the brain.

  1. Rapid, Microwave-Assisted Organic Synthesis of Selective V600EBRAF Inhibitors for Preclinical Cancer Research

    Science.gov (United States)

    Buck, Jason R.; Saleh, Sam; Uddin, Md. Imam; Manning, H. Charles

    2012-01-01

    We report a dramatically improved total synthesis of two highly selective V600EBRAF inhibitors, PLX4720 and PLX4032, that leverages microwave-assisted organic synthesis (MAOS). Compared with previously reported approaches, our novel MAOS method significantly reduces overall reaction time without compromising yield. In addition to providing a gram-scale route to these compounds for preclinical oncology research, we anticipate this approach could accelerate the synthesis of azaindoles in high-throughput, library-based formats. PMID:23180892

  2. The use of purposeful sampling in a qualitative evidence synthesis: A worked example on sexual adjustment to a cancer trajectory

    Directory of Open Access Journals (Sweden)

    Charlotte Benoot

    2016-02-01

    Full Text Available Abstract Background An increasing number of qualitative evidence syntheses papers are found in health care literature. Many of these syntheses use a strictly exhaustive search strategy to collect articles, mirroring the standard template developed by major review organizations such as the Cochrane and Campbell Collaboration. The hegemonic idea behind it is that non-comprehensive samples in systematic reviews may introduce selection bias. However, exhaustive sampling in a qualitative evidence synthesis has been questioned, and a more purposeful way of sampling papers has been proposed as an alternative, although there is a lack of transparency on how these purposeful sampling strategies might be applied to a qualitative evidence synthesis. We discuss in our paper why and how we used purposeful sampling in a qualitative evidence synthesis about ‘sexual adjustment to a cancer trajectory’, by giving a worked example. Methods We have chosen a mixed purposeful sampling, combining three different strategies that we considered the most consistent with our research purpose: intensity sampling, maximum variation sampling and confirming/disconfirming case sampling. Results The concept of purposeful sampling on the meta-level could not readily been borrowed from the logic applied in basic research projects. It also demands a considerable amount of flexibility, and is labour-intensive, which goes against the argument of many authors that using purposeful sampling provides a pragmatic solution or a short cut for researchers, compared with exhaustive sampling. Opportunities of purposeful sampling were the possible inclusion of new perspectives to the line-of-argument and the enhancement of the theoretical diversity of the papers being included, which could make the results more conceptually aligned with the synthesis purpose. Conclusions This paper helps researchers to make decisions related to purposeful sampling in a more systematic and transparent way

  3. Conductive polymer-based nanoparticles for laser-mediated photothermal ablation of cancer: synthesis, characterization, and in vitro evaluation.

    Science.gov (United States)

    Cantu, Travis; Walsh, Kyle; Pattani, Varun P; Moy, Austin J; Tunnell, James W; Irvin, Jennifer A; Betancourt, Tania

    2017-01-01

    Laser-mediated photothermal ablation of cancer cells aided by photothermal agents is a promising strategy for localized, externally controlled cancer treatment. We report the synthesis, characterization, and in vitro evaluation of conductive polymeric nanoparticles (CPNPs) of poly(diethyl-4,4'-{[2,5-bis(2,3-dihydrothieno[3,4-b][1,4]dioxin-5-yl)-1,4-phenylene] bis(oxy)}dibutanoate) (P1) and poly(3,4-ethylenedioxythiophene) (PEDOT) stabilized with 4-dodecylbenzenesulfonic acid and poly(4-styrenesulfonic acid-co-maleic acid) as photothermal ablation agents. The nanoparticles were prepared by oxidative-emulsion polymerization, yielding stable aqueous suspensions of spherical particles of <100 nm diameter as determined by dynamic light scattering and electron microscopy. Both types of nanoparticles show strong absorption of light in the near infrared region, with absorption peaks at 780 nm for P1 and 750 nm for PEDOT, as well as high photothermal conversion efficiencies (~50%), that is higher than commercially available gold-based photothermal ablation agents. The nanoparticles show significant photostability as determined by their ability to achieve consistent temperatures and to maintain their morphology upon repeated cycles of laser irradiation. In vitro studies in MDA-MB-231 breast cancer cells demonstrate the cytocompatibility of the CPNPs and their ability to mediate complete cancer cell ablation upon irradiation with an 808-nm laser, thereby establishing the potential of these systems as agents for laser-induced photothermal therapy.

  4. Conductive polymer-based nanoparticles for laser-mediated photothermal ablation of cancer: synthesis, characterization, and in vitro evaluation

    Science.gov (United States)

    Cantu, Travis; Walsh, Kyle; Pattani, Varun P; Moy, Austin J; Tunnell, James W; Irvin, Jennifer A; Betancourt, Tania

    2017-01-01

    Laser-mediated photothermal ablation of cancer cells aided by photothermal agents is a promising strategy for localized, externally controlled cancer treatment. We report the synthesis, characterization, and in vitro evaluation of conductive polymeric nanoparticles (CPNPs) of poly(diethyl-4,4′-{[2,5-bis(2,3-dihydrothieno[3,4-b][1,4]dioxin-5-yl)-1,4-phenylene] bis(oxy)}dibutanoate) (P1) and poly(3,4-ethylenedioxythiophene) (PEDOT) stabilized with 4-dodecylbenzenesulfonic acid and poly(4-styrenesulfonic acid-co-maleic acid) as photothermal ablation agents. The nanoparticles were prepared by oxidative-emulsion polymerization, yielding stable aqueous suspensions of spherical particles of <100 nm diameter as determined by dynamic light scattering and electron microscopy. Both types of nanoparticles show strong absorption of light in the near infrared region, with absorption peaks at 780 nm for P1 and 750 nm for PEDOT, as well as high photothermal conversion efficiencies (~50%), that is higher than commercially available gold-based photothermal ablation agents. The nanoparticles show significant photostability as determined by their ability to achieve consistent temperatures and to maintain their morphology upon repeated cycles of laser irradiation. In vitro studies in MDA-MB-231 breast cancer cells demonstrate the cytocompatibility of the CPNPs and their ability to mediate complete cancer cell ablation upon irradiation with an 808-nm laser, thereby establishing the potential of these systems as agents for laser-induced photothermal therapy. PMID:28144143

  5. Using Tracer Technology to Characterize Contaminated Pipelines

    Energy Technology Data Exchange (ETDEWEB)

    Maresca, Joseph, W., Jr., Ph.D.; Bratton, Wesley, L., Ph.D., P.E.; Dickerson, Wilhelmina; Hales, Rochelle

    2005-12-30

    The Pipeline Characterization Using Tracers (PCUT) technique uses conservative and partitioning, reactive or other interactive tracers to remotely determine the amount of contaminant within a run of piping or ductwork. The PCUT system was motivated by a method that has been successfully used to characterize subsurface soil contaminants and is similar in operation to that of a gas chromatography column. By injecting a ?slug? of both conservative and partitioning tracers at one end (or section) of the piping and measuring the time history of the concentration of the tracers at the other end (or another section) of the pipe, the presence, location, and amount of contaminant within the pipe or duct can be determined. The tracers are transported along the pipe or duct by a gas flow field, typically air or nitrogen, which has a velocity that is slow enough so that the partitioning tracer has time to interact with the contaminant before the tracer slug completely passes over the contaminate region. PCUT not only identifies the presence of contamination, it also can locate the contamination along the pipeline and quantify the amount of residual. PCUT can be used in support of deactivation and decommissioning (D&D) of piping and ducts that may have been contaminated with hazardous chemicals such as chlorinated solvents, petroleum products, radioactive materials, or heavy metals, such as mercury.

  6. Size-controlled synthesis of biodegradable nanocarriers for targeted and controlled cancer drug delivery using salting out cation

    Indian Academy of Sciences (India)

    Madasamy Hari Balakrishanan; Mariappan Rajan

    2016-02-01

    Research for synthesis of size-controlled carriers is currently challenging one. In this research paper, a method for size-controlled synthesis of biodegradable nanocarriers is proposed and described. Salting out method is suitable for both hydrophilic and hydrophobic drugs for the encapsulation on carriers. This synthetic method is based on polylactic acid (PLA) and non-ionic carboxymethyl cellulose (CMC) composed by CaCl2 as salting out agent. This method permits size-controlled synthesis of particles between 50 and 400 nm simply by varying the concentration of salting out agents. We have prepared cisplatin (CDDP)-loaded PLA-CMC nanocarriers by salting out method, with varying salting out agent (CaCl2) concentrations as 0.05, 0.2, 0.35 and 0.5 M. The nanocarriers were characterized for their size, surface charge and morphology by atomic force microscope, zeta potential analyser and transmission electron microscope, respectively. The encapsulation efficiency and in-vitro drug-releasing behaviour of the nanocarriers were investigated. The cytotoxicity effect of nanocarriers and drug-loaded nanocarriers was tested against MCF-7 breast cancer cell line.

  7. Imaging prostate cancer: an update on positron emission tomography and magnetic resonance imaging

    DEFF Research Database (Denmark)

    Bouchelouche, Kirsten; Turkbey, Baris; Choyke, Peter;

    2010-01-01

    Prostate cancer is a common cancer in men and continues to be a major health problem. Imaging plays an essential role in the clinical management of patients. An important goal for prostate cancer imaging is more accurate disease characterization through the synthesis of anatomic, functional......, and molecular imaging information. Developments in imaging technologies, specifically magnetic resonance imaging (MRI) and positron emission tomography (PET)/computed tomography (CT), have improved the detection rate of prostate cancer. MRI has improved lesion detection and local staging. Furthermore, MRI...... allows functional assessment with techniques such as diffusion-weighted MRI, MR spectroscopy, and dynamic contrast-enhanced MRI. The most common PET radiotracer, (18)F-fluorodeoxyglucose, is not very useful in prostate cancer. However, in recent years other PET tracers have improved the accuracy of PET...

  8. Tracers to investigate protein and amino acid metabolism in human subjects.

    Science.gov (United States)

    Wagenmakers, A J

    1999-11-01

    Three tracer methods have been used to measure protein synthesis, protein breakdown and protein oxidation at whole-body level. The method using L-[1-(13)C]leucine is considered the method of reference. These methods have contributed greatly to the existing knowledge on whole-body protein turnover and its regulation by feeding, fasting, hormones and disease. How exercise and ingestion of mixed protein-containing meals affect whole-body protein metabolism is still open to debate, as there are discrepancies in results obtained with different tracers. The contribution of whole-body methods to the future gain of knowledge is expected to be limited due to the fact that most physiological disturbances have been investigated extensively, and due to the lack of information on the relative contribution of various tissues and proteins to whole-body changes. Tracer amino acid-incorporation methods are most suited to investigate these latter aspects of protein metabolism. These methods have shown that some tissues (liver and gut) have much higher turnover rates and deposit much more protein than others (muscle). Massive differences also exist between the fractional synthesis rates of individual proteins. The incorporation methods have been properly validated, although minor disagreements remain on the identity of the true precursor pool (the enrichment of which should be used in the calculations). Arterio-venous organ balance studies have shown that little protein is deposited in skeletal muscle following a protein-containing meal, while much more protein is deposited in liver and gut. The amount deposited in the feeding period in each of these tissues is released again during overnight fasting. The addition of tracers to organ balance studies allows the simultaneous estimation of protein synthesis and protein breakdown, and provides information on whether changes in net protein balance are caused primarily by a change in protein synthesis or in protein breakdown. In the case

  9. The Copenhagen tracer experiments: Reporting of measurements

    DEFF Research Database (Denmark)

    Gryning, Sven-Erik; Lyck, E.

    2002-01-01

    buoyancy from a tower at a height of 115 meters and then collected 2-3 meters above ground-level at positions in up to three crosswind arcs of tracer sampling units, positioned 2-6 km from the point of release. Three consecutive 20 min averaged tracer concentrations were measured, allowing for a total...... sampling time of 1 hour. The site was mainly residential having a roughness length of 0.6 m. The meteorological measurements performed during the experimentsincluded standard measurements along the tower of tracer release as well as the three-dimensional wind velocity fluctuations at the height of release....

  10. Green synthesis of graphene and its cytotoxic effects in human breast cancer cells

    Directory of Open Access Journals (Sweden)

    Gurunathan S

    2013-03-01

    Full Text Available Sangiliyandi Gurunathan, Jae Woong Han, Vasuki Eppakayala, Jin-Hoi Kim Department of Animal Biotechnology, Konkuk University, Seoul, South Korea Background: This paper describes an environmentally friendly (“green” approach for the synthesis of soluble graphene using Bacillus marisflavi biomass as a reducing and stabilizing agent under mild conditions in aqueous solution. In addition, the study reported here investigated the cytotoxicity effects of graphene oxide (GO and bacterially reduced graphene oxide (B-rGO on the inhibition of cell viability, reactive oxygen species (ROS generation, and membrane integrity in human breast cancer cells. Methods: The reduction of GO was characterized by ultraviolet–visible spectroscopy. Size distribution was analyzed by dynamic light scattering. Further, X-ray diffraction and high-resolution scanning electron microscopy were used to investigate the crystallinity of graphene and the morphologies of prepared graphene, respectively. The formation of defects further supports the bio-functionalization of graphene, as indicated in the Raman spectrum of B-rGO. Surface morphology and the thickness of the GO and B-rGO were analyzed using atomic force microscopy, while the biocompatibility of GO and B-rGO were investigated using WST-8 assays on MCF-7 cells. Finally, cellular toxicity was evaluated by ROS generation and membrane integrity assays. Results: In this study, we demonstrated an environmentally friendly, cost-effective, and simple method for the preparation of water-soluble graphene using bacterial biomass. This reduction method avoids the use of toxic reagents such as hydrazine and hydrazine hydrate. The synthesized soluble graphene was confirmed using various analytical techniques. Our results suggest that both GO and B-rGO exhibit toxicity to MCF-7 cells in a dose-dependent manner, with a dose > 60 µg/mL exhibiting obvious cytotoxicity effects, such as decreasing cell viability, increasing ROS

  11. Design, synthesis, and evaluation of asymmetric EF24 analogues as potential anti-cancer agents for lung cancer.

    Science.gov (United States)

    Wu, Jianzhang; Wu, Shoubiao; Shi, Lingyi; Zhang, Shanshan; Ren, Jiye; Yao, Song; Yun, Di; Huang, Lili; Wang, Jiabing; Li, Wulan; Wu, Xiaoping; Qiu, Peihong; Liang, Guang

    2017-01-05

    The nuclear factor-kappa B (NF-κB) signaling pathway has been targeted for the therapy of various cancers, including lung cancer. EF24 was considered as a potent inhibitor of NF-κB signaling pathway. In this study, a series of asymmetric EF24 analogues were synthesized and evaluated for their anti-cancer activity against three lung cancer cell lines (A549, LLC, H1650). Most of the compounds exhibited good anti-tumor activity. Among them, compound 81 showed greater cytotoxicity than EF24. Compound 81 also possessed a potent anti-migration and anti-proliferative ability against A549 cells in a concentration-dependent manner. Moreover, compound 81 induced lung cancer cells death by inhibiting NF-κB signaling pathway, and activated the JNK-mitochondrial apoptotic pathway by increasing reactive oxygen species (ROS) generation resulting in apoptosis. In summary, compound 81 is a valuable candidate for anti-lung cancer therapy.

  12. Compartmental modeling and tracer kinetics

    CERN Document Server

    Anderson, David H

    1983-01-01

    This monograph is concerned with mathematical aspects of compartmental an­ alysis. In particular, linear models are closely analyzed since they are fully justifiable as an investigative tool in tracer experiments. The objective of the monograph is to bring the reader up to date on some of the current mathematical prob­ lems of interest in compartmental analysis. This is accomplished by reviewing mathematical developments in the literature, especially over the last 10-15 years, and by presenting some new thoughts and directions for future mathematical research. These notes started as a series of lectures that I gave while visiting with the Division of Applied ~1athematics, Brown University, 1979, and have developed in­ to this collection of articles aimed at the reader with a beginning graduate level background in mathematics. The text can be used as a self-paced reading course. With this in mind, exercises have been appropriately placed throughout the notes. As an aid in reading the material, the e~d of a ...

  13. In silico inspired design and synthesis of a novel tubulin-binding anti-cancer drug: folate conjugated noscapine (Targetin)

    Science.gov (United States)

    Naik, Pradeep K.; Lopus, Manu; Aneja, Ritu; Vangapandu, Surya N.; Joshi, Harish C.

    2012-02-01

    Our screen for tubulin-binding small molecules that do not depolymerize bulk cellular microtubules, but based upon structural features of well known microtubule-depolymerizing colchicine and podophyllotoxin, revealed tubulin binding anti-cancer property of noscapine (Ye et al. in Proc Natl Acad Sci USA 95:2280-2286, 1998). Guided by molecular modelling calculations and structure-activity relationships we conjugated at C9 of noscapine, a folate group—a ligand for cellular folate receptor alpha (FRα). FRα is over-expressed on some solid tumours such as ovarian epithelial cancers. Molecular docking experiments predicted that a folate conjugated noscapine (Targetin) accommodated well inside the binding cavity (docking score -11.295 kcal/mol) at the interface between α- and β-tubulin. The bulky folate moiety of Targetin is extended toward lumen of microtubules. The binding free energy (Δ G bind) computed based on molecular mechanics energy minimization was -221.01 kcal/mol that revealed favourable interaction of Targetin with the receptor. Chemical synthesis, tubulin-binding experiments, and anti-cancer activity in vitro corroborate fully well with the molecular modelling experiments. Targetin binds tubulin with a dissociation constant ( K d value) of 149 ± 3.0 μM and decreases the transition frequencies between growth and shortening phases of microtubule assembly dynamics at concentrations that do not alter the total polymer mass. Cancer cells in general were more sensitive to Targetin compared with the founding compound noscapine (IC50 in the range of 15-40 μM). Quite strikingly, ovarian cancer cells (SKOV3 and A2780), known to overexpress FRα, were much more sensitive to targetin (IC50 in the range of 0.3-1.5 μM).

  14. In silico inspired design and synthesis of a novel tubulin-binding anti-cancer drug: folate conjugated noscapine (Targetin).

    Science.gov (United States)

    Naik, Pradeep K; Lopus, Manu; Aneja, Ritu; Vangapandu, Surya N; Joshi, Harish C

    2012-02-01

    Our screen for tubulin-binding small molecules that do not depolymerize bulk cellular microtubules, but based upon structural features of well known microtubule-depolymerizing colchicine and podophyllotoxin, revealed tubulin binding anti-cancer property of noscapine (Ye et al. in Proc Natl Acad Sci USA 95:2280-2286, 1998). Guided by molecular modelling calculations and structure-activity relationships we conjugated at C9 of noscapine, a folate group-a ligand for cellular folate receptor alpha (FRα). FRα is over-expressed on some solid tumours such as ovarian epithelial cancers. Molecular docking experiments predicted that a folate conjugated noscapine (Targetin) accommodated well inside the binding cavity (docking score -11.295 kcal/mol) at the interface between α- and β-tubulin. The bulky folate moiety of Targetin is extended toward lumen of microtubules. The binding free energy (ΔG (bind)) computed based on molecular mechanics energy minimization was -221.01 kcal/mol that revealed favourable interaction of Targetin with the receptor. Chemical synthesis, tubulin-binding experiments, and anti-cancer activity in vitro corroborate fully well with the molecular modelling experiments. Targetin binds tubulin with a dissociation constant (K (d) value) of 149 ± 3.0 μM and decreases the transition frequencies between growth and shortening phases of microtubule assembly dynamics at concentrations that do not alter the total polymer mass. Cancer cells in general were more sensitive to Targetin compared with the founding compound noscapine (IC(50) in the range of 15-40 μM). Quite strikingly, ovarian cancer cells (SKOV3 and A2780), known to overexpress FRα, were much more sensitive to targetin (IC(50) in the range of 0.3-1.5 μM).

  15. The Application of Tracer Method for SLN Localization and Testing with Methylene Blue Breast Glands Axillary Tail Injection in the Treatment of Early Breast Cancer%美蓝腋尾部注射示踪哨兵淋巴结定位及检测在早期乳腺癌治疗中的应用

    Institute of Scientific and Technical Information of China (English)

    王帅; 尚春力; 孙宝杰

    2015-01-01

    目的:研究乳腺腺体腋尾部注射美蓝示踪哨兵淋巴结法及哨兵淋巴结活检(SLNB)的临床应用。方法应用美蓝腋尾部注射法对44例乳腺癌患者行SLNB,随后行乳腺癌改良根治术。结果哨兵淋巴结SLN的检出率为93.2%,准确性为88.2%,敏感性为93.8%,假阴性率为11.8%,SLNB与ALND阳性率比较无统计学差异。结论美蓝腋尾部注射示踪哨兵淋巴结技术可应用于临床,SLNB活检可用于预测腋窝淋巴结转移情况。%Objective The purpose of this paper is to study the clinical application of tracer method for SLN with methylene blue breast glands axillary tail injection and the sentinel lymph node biopsy (SLNB). Methods The method described in this paper is to apply methylene blue breast glands axillary tail injection to 44 breast cancer cases and perform modiifed radical mastectomy successively. Results The result shows that the detection rate of SLN was 93.2%, accuracy was of 88.2%, sensitivity was of 93.8%, and false-negative rate was of 11.8%. There was no statistical difference of positive rate between SLNB and axillary lymph node dissection (ALND). Conclusion This paper concludes that the technology of SLN tracer method with methylene blue breast glands axillary tail injection can be applied in clinic and SLNB can be applied in prognosis of axillary lymph node metastasis (ALNM).

  16. Chemotherapy triggers HIF-1-dependent glutathione synthesis and copper chelation that induces the breast cancer stem cell phenotype.

    Science.gov (United States)

    Lu, Haiquan; Samanta, Debangshu; Xiang, Lisha; Zhang, Huimin; Hu, Hongxia; Chen, Ivan; Bullen, John W; Semenza, Gregg L

    2015-08-18

    Triple negative breast cancer (TNBC) accounts for 10-15% of all breast cancer but is responsible for a disproportionate share of morbidity and mortality because of its aggressive characteristics and lack of targeted therapies. Chemotherapy induces enrichment of breast cancer stem cells (BCSCs), which are responsible for tumor recurrence and metastasis. Here, we demonstrate that chemotherapy induces the expression of the cystine transporter xCT and the regulatory subunit of glutamate-cysteine ligase (GCLM) in a hypoxia-inducible factor (HIF)-1-dependent manner, leading to increased intracellular glutathione levels, which inhibit mitogen-activated protein kinase kinase (MEK) activity through copper chelation. Loss of MEK-ERK signaling causes FoxO3 nuclear translocation and transcriptional activation of the gene encoding the pluripotency factor Nanog, which is required for enrichment of BCSCs. Inhibition of xCT, GCLM, FoxO3, or Nanog blocks chemotherapy-induced enrichment of BCSCs and impairs tumor initiation. These results suggest that, in combination with chemotherapy, targeting BCSCs by inhibiting HIF-1-regulated glutathione synthesis may improve outcome in TNBC.

  17. A novel green one-step synthesis of gold nanoparticles using crocin and their anti-cancer activities.

    Science.gov (United States)

    Hoshyar, Reyhane; Khayati, Gholam Reza; Poorgholami, Maliheh; Kaykhaii, Massoud

    2016-06-01

    Functionalized nanoparticles are specifically designed to deliver drugs at tumor cells and can potentially enhance anticancer activity of drugs such as crocin. In the present study, we have applied antioxidant crocin as a reducing agent for one pot green synthesis of controlled size gold nanoparticles (AuNPs). Spherical, stable and uniform AuNPs were synthesized using crocin. These AuNPs are characterized by UV-Vis, TEM and XRD techniques. The prepared AuNPs showed surface plasm on resonance centered at 520nm with the average particle size of about 4-10nm. The anti-cancer effect of AuNPs was determined using MTT and LDH tests. The cellular data showed that these AuNPs significantly decreased cancerous cells' growth after 24 and 48hours in a time- and dose-dependent manner (P<0.05). The results suggest that such AuNPs can be synthesized simply and quickly with invaluable clinical as well as pharmaceutical activities which can help to treat human breast cancer.

  18. Tracers in oncology. Preclinical and clinical evaluation; Innovative Tracer in der onkologischen Diagnostik. Praeklinische und klinische Evaluierung

    Energy Technology Data Exchange (ETDEWEB)

    Krause, B.J.; Schwarzenboeck, S.; Schwaiger, M. [Technische Univ. Muenchen, Klinikum rechts der Isar (Germany). Klinik und Poliklinik fuer Nuklearmedizin

    2010-07-01

    In oncology, PET and PET/CT with tracers beyond FDG target more specific biological processes, such as proliferation ({sup 18}F-3'-fluoro-3'-deoxy-L-thymidine; {sup 18}F-FLT), tumour hypoxia ({sup 18}F-fluoromisonidazol; {sup 18}F-FMISO) and phospholipid metabolism (radioactively labelled choline derivates). FLT is a thymidine analogue which can be labelled with {sup 18}F. PET with {sup 18}F-FLT enables to non-invasively image and to quantify the proliferation fraction of tumours. Proliferation dependent accumulation of FLT has been demonstrated for a variety of solid and haematologic neoplasms including lung cancer, breast cancer, gastric cancer, colorectal cancer and malignant lymphoma. Furthermore, FLT has been suggested as surrogate marker for the assessment of response to treatment, especially when targeted drugs are utilized. PET imaging in particular has emerged as a promising non-invasive tool to accurately characterize tumour oxygenation. The great promise of PET/CT is its potential as a single imaging modality for whole body staging that provides anatomical and biological information on the disease as a whole. It allows a more precise estimation of the hypoxic tumour volume as well as comparisons on a voxel-by-voxel basis (parametric mapping). PET and PET/CT with hypoxia tracers thus offer the potential to optimize and individualize therapy for patients suffering from cancer. PET- and PET/CT-studies using {sup 11}C- or {sup 18}F-labeled choline derivates recently have shown promising results for re-staging prostate cancer in patients with biochemical recurrence and advanced prostate cancer. In patients with biochemical recurrence of prostate cancer after primary therapy the detection rate of {sup 11}C-choline- PET/CT shows a positive relationship with serum PSA-levels. In these patients {sup 11}C-choline PET/CT allows not only to diagnose but also to localize recurrent disease with implications on disease management (localised vs. systemic

  19. 染料示踪法联合荧光示踪法提高乳腺癌前哨淋巴结活检术成功率%Success Rate of Sentinel Lymph Node Biopsy in Breast Cancer Increased by Combined Tracer Method of Fluorescence and Dye

    Institute of Scientific and Technical Information of China (English)

    崔嵘嵘; 林晓燕; 许诚; 胡贇宏; 王铮元; 蔡丰丰

    2016-01-01

    杂作用后,采用染料示踪法联合荧光示踪法 SLNB 成功率高于采用染料示踪法(χ2MH=26.686,P ﹤0.001,ORMH =3.928)。Logistic 回归分析结果显示,示踪法、BMI、年龄是 SLNB 结果的影响因素(P﹤0.05)。Logistic 回归模型分类预测准确率为80.2%。结论染料示踪法联合荧光示踪法可有效提高乳腺癌 SLNB 成功率,值得临床推荐使用。%Background The sentinel lymph node biopsy(SLNB)of breast cancer is gaining increased attention in recent years,and the choosing of tracer is of great importance in its success rate. Objective To evaluate the clinical effectiveness and application value of the combined tracer method of fluorescence and dye in SLNB of breast cancer. Methods According to the inclusion criteria of the study,449 patients with primarily invasive breast cancer,who received treatment in Department of Breast Surgery of Yangpu Hospital,Tongji University from January 2010 to September 2015,were selected as research objects. Patients were divided into group A(226 patients with dye tracer method)and group B(223 patients with the combined tracer method of fluorescence and dye)by random number table method. The general information〔 including age,body mass index(BMI)〕of patients were collected,the success rate of patients' SLNB were calculated. Stratified analysis of patients were made based on their BMI(≤22. 5 kg/ m2 and ﹥ 22. 5 kg/ m2 )and age(≤55 and ﹥ 55). Results BMI and age in group A were less than those in group B(P ﹤ 0. 05). Among the 223 patients(BMI≤22. 5 kg/ m2 ),the success rate of SLNB with combined tracer method of fluorescence and dye〔94. 7%(108 / 114)〕was higher than that of SLNB with dye tracer method〔78. 0%(85 / 109)〕〔OR = 5. 082,95% CI(1. 988,12. 993)〕. Among the 226 patients(BMI ﹥ 22. 5 kg/ m2 ),the success rate of SLNB with combined tracer method of fluorescence and dye〔85. 3%(93 / 109)〕was higher than that of SLNB with dye

  20. Analysis of tracer and thermal transients during reinjection

    Energy Technology Data Exchange (ETDEWEB)

    Kocabas, I.

    1989-10-01

    This work studied tracer and thermal transients during reinjection in geothermal reserviors and developed a new technique which combines the results from interwell tracer tests and thermal injection-backflow tests to estimate the thermal breakthrough times. Tracer tests are essential to determine the degree of connectivity between the injection wells and the producing wells. To analyze the tracer return profiles quantitatively, we employed three mathematical models namely, the convection-dispersion (CD) model, matrix diffusion (MD) model, and the Avodnin (AD) model, which were developed to study tracer and heat transport in a single vertical fracture. We considered three types of tracer tests namely, interwell tracer tests without recirculation, interwell tracer tests with recirculation, and injection-backflow tracer tests. To estimate the model parameters, we used a nonlinear regression program to match tracer return profiles to the solutions.

  1. Evaluation of leakage from fume hoods using tracer gas, tracer nanoparticles and nanopowder handling test methodologies.

    Science.gov (United States)

    Dunn, Kevin H; Tsai, Candace Su-Jung; Woskie, Susan R; Bennett, James S; Garcia, Alberto; Ellenbecker, Michael J

    2014-01-01

    The most commonly reported control used to minimize workplace exposures to nanomaterials is the chemical fume hood. Studies have shown, however, that significant releases of nanoparticles can occur when materials are handled inside fume hoods. This study evaluated the performance of a new commercially available nano fume hood using three different test protocols. Tracer gas, tracer nanoparticle, and nanopowder handling protocols were used to evaluate the hood. A static test procedure using tracer gas (sulfur hexafluoride) and nanoparticles as well as an active test using an operator handling nanoalumina were conducted. A commercially available particle generator was used to produce sodium chloride tracer nanoparticles. Containment effectiveness was evaluated by sampling both in the breathing zone (BZ) of a mannequin and operator as well as across the hood opening. These containment tests were conducted across a range of hood face velocities (60, 80, and 100 ft/min) and with the room ventilation system turned off and on. For the tracer gas and tracer nanoparticle tests, leakage was much more prominent on the left side of the hood (closest to the room supply air diffuser) although some leakage was noted on the right side and in the BZ sample locations. During the tracer gas and tracer nanoparticle tests, leakage was primarily noted when the room air conditioner was on for both the low and medium hood exhaust airflows. When the room air conditioner was turned off, the static tracer gas tests showed good containment across most test conditions. The tracer gas and nanoparticle test results were well correlated showing hood leakage under the same conditions and at the same sample locations. The impact of a room air conditioner was demonstrated with containment being adversely impacted during the use of room air ventilation. The tracer nanoparticle approach is a simple method requiring minimal setup and instrumentation. However, the method requires the reduction in

  2. Journal: A Review of Some Tracer-Test Design Equations for Tracer-Mass Estimation and Sample Collection Frequency

    Science.gov (United States)

    Determination of necessary tracer mass, initial sample-collection time, and subsequent sample-collection frequency are the three most difficult aspects to estimate for a proposed tracer test prior to conducting the tracer test. To facilitate tracer-mass estimation, 33 mass-estima...

  3. Targeting monocyte chemotactic protein-1 synthesis with bindarit induces tumor regression in prostate and breast cancer animal models.

    Science.gov (United States)

    Zollo, Massimo; Di Dato, Valeria; Spano, Daniela; De Martino, Daniela; Liguori, Lucia; Marino, Natascia; Vastolo, Viviana; Navas, Luigi; Garrone, Beatrice; Mangano, Giorgina; Biondi, Giuseppe; Guglielmotti, Angelo

    2012-08-01

    Prostate and breast cancer are major causes of death worldwide, mainly due to patient relapse upon disease recurrence through formation of metastases. Chemokines are small proteins with crucial roles in the immune system, and their regulation is finely tuned in early inflammatory responses. They are key molecules during inflammatory processes, and many studies are focusing on their regulatory functions in tumor growth and angiogenesis during metastatic cell seeding and spreading. Bindarit is an anti-inflammatory indazolic derivative that can inhibit the synthesis of MCP-1/CCL2, with a potential inhibitory function in tumor progression and metastasis formation. We show here that in vitro, bindarit can modulate cancer-cell proliferation and migration, mainly through negative regulation of TGF-β and AKT signaling, and it can impair the NF-κB signaling pathway through enhancing the expression of the NF-κB inhibitor IkB-α. In vivo administration of bindarit results in impaired metastatic disease in prostate cancer xenograft mice (PC-3M-Luc2 cells injected intra-cardially) and impairment of local tumorigenesis in syngeneic Balb/c mice injected under the mammary gland with murine breast cancer cells (4T1-Luc cells). In addition, bindarit treatment significantly decreases the infiltration of tumor-associated macrophages and myeloid-derived suppressor cells in 4T1-Luc primary tumors. Overall, our data indicate that bindarit is a good candidate for new therapies against prostate and breast tumorigenesis, with an action through impairment of inflammatory cell responses during formation of the tumor-stroma niche microenvironment.

  4. Green synthesis, characterization of gold and silver nanoparticles and their potential application for cancer therapeutics.

    Science.gov (United States)

    Patra, Sujata; Mukherjee, Sudip; Barui, Ayan Kumar; Ganguly, Anirban; Sreedhar, Bojja; Patra, Chitta Ranjan

    2015-08-01

    In the present article, we demonstrate the delivery of anti-cancer drug to the cancer cells using biosynthesized gold and silver nanoparticles (b-AuNP & b-AgNP). The nanoparticles synthesized by using Butea monosperma (BM) leaf extract are thoroughly characterized by various analytical techniques. Both b-AuNP and b-AgNP are stable in biological buffers and biocompatible towards normal endothelial cells (HUVEC, ECV-304) as well as cancer cell lines (B16F10, MCF-7, HNGC2 & A549). Administration of nanoparticle based drug delivery systems (DDSs) using doxorubicin (DOX) [b-Au-500-DOX and b-Ag-750-DOX] shows significant inhibition of cancer cell proliferation (B16F10, MCF-7) compared to pristine drug. Therefore, we strongly believe that biosynthesized nanoparticles will be useful for the development of cancer therapy using nanomedicine approach in near future.

  5. Tracer-based prediction of thermal reservoir lifetime: scope, limitations, and the role of thermosensitive tracers

    Science.gov (United States)

    Ghergut, I.; Behrens, H.; Karmakar, S.; Licha, T.; Nottebohm, M.; Sauter, M.

    2012-04-01

    Thermal-lifetime prediction is a traditional endeavour of inter-well tracer tests conducted in geothermal reservoirs. Early tracer test signals (detectable within the first few years of operation) are expected to correlate with late-time production temperature evolutions ('thermal breakthrough', supposed to not occur before some decades of operation) of a geothermal reservoir. Whenever a geothermal reservoir can be described as a single-fracture system, its thermal lifetime will, ideally, be determined by two parameters (say, fracture aperture and porosity), whose inversion from conservative-tracer test signals is straightforward and non-ambiguous (provided that the tracer tests, and their interpretation, are performed in accordance to the rules of the art). However, as soon as only 'few more' fractures are considered, this clear-cut correlation is broken. A given geothermal reservoir can simultaneously feature a single-fracture behaviour, in terms of heat transport, and a multiple-fracture behaviour, in terms of solute tracer transport (or vice-versa), whose effective values of fracture apertures, spacings, and porosities are essentially uncorrelated between heat and solute tracers. Solute transport parameters derived from conservative-tracer tests will no longer characterize the heat transport processes (and thus temperature evolutions) taking place in the same reservoir. Parameters determining its thermal lifetime will remain 'invisible' to conservative tracers in inter-well tests. We demonstrate this issue at the example of a five-fracture system, representing a deep-geothermal reservoir, with well-doublet placement inducing fluid flow 'obliquely' to the fractures. Thermal breakthrough in this system is found to strongly depend on fracture apertures, whereas conservative-solute tracer signals from inter-well tests in the same system do not show a clear-cut correlation with fracture apertures. Only by using thermosensitive substances as tracers, a reliable

  6. Synthesis of Hexagonal ZnO-PQ7 Nano Disks Conjugated with Folic Acid to Image MCF - 7 Cancer Cells.

    Science.gov (United States)

    Sureshkumar, S; Jothimani, B; Sridhar, T M; Santhosh, Arul; Venkatachalapathy, B

    2017-01-01

    Surface modified ZnO nanomaterial is widely used in the field of bioimaging worldwide due to its optical properties, electronic characteristics and biocompatibility. Fluorescent enhanced, Polyquaternium-7(PQ7) capped, ZnO hexagonal nano disks (ZnO-PQ7) were synthesised by simple wet chemical method. The structural and optical properties of ZnO-PQ7 hexagonal nano disks were characterized using XRD, UV-Visible, Fluorescence, HRTEM, EDAX and FTIR studies. The size of synthesised ZnO-PQ7 were around 30-45 nm as confirmed by HRTEM studies. Fluorescence emission intensity increased with increase in PQ7 concentration. ZnO-PQ7 was further conjugated with folic acid (FA) to target human breast cancer cell line (MCF-7) via EDC/NHS coupling chemistry. Conjugation of folic acid with ZnO-PQ7 was confirmed by FTIR studies. The cell viability study using Methyl thiazolyltetrazolium(MTT) assay has demonstrated that the ZnO-PQ7 conjugated FA composites (ZnO-PQ7-FA) exhibit low toxicity towards MCF-7 up to a concentration of 125 μg/mL. Confocal laser scanning microscopic images confirmed the uptake of ZnO-PQ7-FA nanoparticles by MCF-7 cells. This study reveals ZnO-PQ7-FA nano disks as a potential imaging agent for detection of cancer cells. The synthesis route reported in this article is simple and easy to follow for the synthesis of ZnO-PQ7-FA in bulk quantities with high purity.

  7. Effect of Eicosapentaenoic Acid on E-type Prostaglandin Synthesis and EP4 Receptor Signaling Human Colorectal Cancer Cells

    Directory of Open Access Journals (Sweden)

    Gillian Hawcroft

    2010-08-01

    Full Text Available The ω-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA, in the free fatty acid (FFA form, has been demonstrated to reduce adenoma number and size in patients with familial adenomatous polyposis. However, the mechanistic basis of the antineoplastic activity of EPA in the colorectum remains unclear. We tested the hypothesis that EPAFFA negatively modulates synthesis of and signaling by prostaglandin (PG E2 in human colorectal cancer (CRC cells. EPA-FFA induced apoptosis of cyclooxygenase (COX-2-positive human HCA-7 CRC cells in vitro. EPA-FFA in cell culture medium was incorporated rapidly into phospholipid membranes of HCA-7 human CRC cells and acted as a substrate for COX-2, leading to reduced synthesis of PGE2 and generation of PGE3. Alone, PGE3 bound and activated the PGE2 EP4 receptor but with reduced affinity and efficacy compared with its “natural” ligand PGE2. However, in the presence of PGE2, PGE3 acted as an antagonist of EP4 receptor-dependent 3’,5’ cyclic adenosine monophosphate induction in naturally EP4 receptor-positive LoVo human CRC cells and of resistance to apoptosis in HT-29-EP4 human CRC cells overexpressing the EP4 receptor. We conclude that EPA-FFA drives a COX-2dependent “PGE2-to-PGE3 switch” in human CRC cells and that PGE3 acts as a partial agonistat the PGE2 EP4 receptor.

  8. Green synthesis, characterization of gold and silver nanoparticles and their potential application for cancer therapeutics

    Energy Technology Data Exchange (ETDEWEB)

    Patra, Sujata; Mukherjee, Sudip; Barui, Ayan Kumar; Ganguly, Anirban [Biomaterials Group, CSIR-Indian Institute of Chemical Technology, Uppal Road, Tarnaka, Hyderabad 500007, Telangana State (India); Sreedhar, Bojja [Inorganic and Physical Chemistry Division, CSIR-Indian Institute of Chemical Technology, Uppal Road, Tarnaka, Hyderabad 500007, Telangana State (India); Patra, Chitta Ranjan, E-mail: crpatra@iict.res.in [Biomaterials Group, CSIR-Indian Institute of Chemical Technology, Uppal Road, Tarnaka, Hyderabad 500007, Telangana State (India)

    2015-08-01

    In the present article, we demonstrate the delivery of anti-cancer drug to the cancer cells using biosynthesized gold and silver nanoparticles (b-AuNP & b-AgNP). The nanoparticles synthesized by using Butea monosperma (BM) leaf extract are thoroughly characterized by various analytical techniques. Both b-AuNP and b-AgNP are stable in biological buffers and biocompatible towards normal endothelial cells (HUVEC, ECV-304) as well as cancer cell lines (B16F10, MCF-7, HNGC2 & A549). Administration of nanoparticle based drug delivery systems (DDSs) using doxorubicin (DOX) [b-Au-500-DOX and b-Ag-750-DOX] shows significant inhibition of cancer cell proliferation (B16F10, MCF-7) compared to pristine drug. Therefore, we strongly believe that biosynthesized nanoparticles will be useful for the development of cancer therapy using nanomedicine approach in near future. - Highlights: • Biosynthesis of gold and silver nanoparticles using plant leaf extract • The approach is clean, efficient, eco-friendly & economically safe. • Biosynthesized nanoparticles are biocompatible towards normal and cancer cells. • Design and development of biosynthesized nanoparticle based drug delivery systems • Biosynthesized nanoparticles could be useful for cancer and other diseases.

  9. Testing and comparison of four ionic tracers to measure stream flow loss by multiple tracer injection

    Science.gov (United States)

    Zellweger, G.W.

    1994-01-01

    An injectate containing lithium, sodium, chloride and bromide was added continuously at five sites along a 507 m study reach of St Kevin Gulch, Lake County, Colorado to determine which sections of the stream were losing water to the stream bed and to ascertain how well the four tracers performed. The acidity of the stream (pH 3.6) made it possible for lithium and sodium, which are normally absorbed by ion exchange with stream bed sediment, to be used as conservative tracers. Net flow losses as low as 0.81 s-1, or 8% of flow, were calculated between measuring sites. By comparing the results of simultaneous injection it was determined whether subsections of the study reach were influent or effluent. Evaluation of tracer concentrations along 116 m of stream indicated that all four tracers behaved conservatively. Discharges measured by Parshall flumes were 4-18% greater than discharges measured by tracer dilution. -from Author

  10. TRACER - TRACING AND CONTROL OF ENGINEERING REQUIREMENTS

    Science.gov (United States)

    Turner, P. R.

    1994-01-01

    TRACER (Tracing and Control of Engineering Requirements) is a database/word processing system created to document and maintain the order of both requirements and descriptive material associated with an engineering project. A set of hierarchical documents are normally generated for a project whereby the requirements of the higher level documents levy requirements on the same level or lower level documents. Traditionally, the requirements are handled almost entirely by manual paper methods. The problem with a typical paper system, however, is that requirements written and changed continuously in different areas lead to misunderstandings and noncompliance. The purpose of TRACER is to automate the capture, tracing, reviewing, and managing of requirements for an engineering project. The engineering project still requires communications, negotiations, interactions, and iterations among people and organizations, but TRACER promotes succinct and precise identification and treatment of real requirements separate from the descriptive prose in a document. TRACER permits the documentation of an engineering project's requirements and progress in a logical, controllable, traceable manner. TRACER's attributes include the presentation of current requirements and status from any linked computer terminal and the ability to differentiate headers and descriptive material from the requirements. Related requirements can be linked and traced. The program also enables portions of documents to be printed, individual approval and release of requirements, and the tracing of requirements down into the equipment specification. Requirement "links" can be made "pending" and invisible to others until the pending link is made "binding". Individuals affected by linked requirements can be notified of significant changes with acknowledgement of the changes required. An unlimited number of documents can be created for a project and an ASCII import feature permits existing documents to be incorporated

  11. Genetic variation in genes of the fatty acid synthesis pathway and breast cancer risk

    DEFF Research Database (Denmark)

    Campa, Daniele; McKay, James; Sinilnikova, Olga

    2009-01-01

    -binding protein), which is induced by glucose, and SREBP-1 (sterol response element-binding protein-1), which is stimulated by insulin through the PI3K/Akt signal transduction pathway. We investigated whether the genetic variability of the genes encoding for ChREBP, SREBP and FAS (respectively, MLXIPL, SREBF1...... and FASN) is related to breast cancer risk and body-mass index (BMI) by studying 1,294 breast cancer cases and 2,452 controls from the European Prospective Investigation on Cancer (EPIC). We resequenced the FAS gene and combined information of SNPs found by resequencing and SNPs from public databases....... Using a tagging approach and selecting 20 SNPs, we covered all the common genetic variation of these genes. In this study we were not able to find any statistically significant association between the SNPs in the FAS, ChREBP and SREPB-1 genes and an increased risk of breast cancer overall...

  12. Acupoints Stimulation for Anxiety and Depression in Cancer Patients: A Quantitative Synthesis of Randomized Controlled Trials

    OpenAIRE

    2016-01-01

    This study aims at concluding the current evidence on the therapeutic effects of acupoints stimulation for cancer patients with anxiety and depression. Randomized controlled trials using acupoints stimulation for relieving anxiety and/or depression in cancer patients were searched, and 11 studies were finally included, of which eight trials compared acupoints stimulation with standard methods of treatment/care, and acupoints stimulation showed significantly better effects in improving depress...

  13. Glycogen synthesis is induced in hypoxia by the hypoxia-inducible factor and promotes cancer cell survival

    Directory of Open Access Journals (Sweden)

    Joffrey ePelletier

    2012-02-01

    Full Text Available The hypoxia-inducible factor 1 (HIF-1, in addition to genetic and epigenetic changes, is largely responsible for alterations in cell metabolism in hypoxic tumor cells. This transcription factor not only favors cell proliferation through the metabolic shift from oxidative phosphorylation to glycolysis and lactic acid production but also stimulates nutrient supply by mediating adaptive survival mechanisms. In this study we showed that glycogen synthesis is enhanced in non-cancer and cancer cells when exposed to hypoxia, resulting in a large increase in glycogen stores. Furthermore, we demonstrated that the mRNA and protein levels of the first enzyme of glycogenesis, phosphoglucomutase1 (PGM1, were increased in hypoxia. We showed that induction of glycogen storage as well as PGM1 expression were dependent on HIF-1 and HIF-2. We established that hypoxia-induced glycogen stores are rapidly mobilized in cells that are starved of glucose. Glycogenolysis allows these hypoxia-preconditioned cells to confront and survive glucose deprivation. In contrast normoxic control cells exhibit a high rate of cell death following glucose removal. These findings point to the important role of hypoxia and HIF in inducing mechanisms of rapid adaptation and survival in response to a decrease in oxygen tension. We propose that a decrease in pO2 acts as an alarm that prepares the cells to face subsequent nutrient depletion and to survive.

  14. One-pot synthesis of gold nanostars using plant polyphenols for cancer photoacoustic imaging and photothermal therapy

    Science.gov (United States)

    Zhang, Xiao-Long; Zheng, Cheng; Zhang, Yun; Yang, Huang-Hao; Liu, Xiaolong; Liu, Jingfeng

    2016-07-01

    Branched plasmonic nanostructures have been found to exhibit strong enhancement of the electromagnetic field surrounding their multi-branched petals. This feature endows them with improved performance in catalysis, surface-enhanced Raman scattering, photoacoustic imaging, and photothermal therapy. Albeit several synthesis techniques have been developed, the precisely controlled growth of highly branched nanostructures with a one-pot surfactant-free procedure is still challenging. Herein, we present a simple seedless route to synthesize gold nanostars (AuNSs) using a natural plant polyphenol, gallic acid (GA), as a reducing and stabilizing agent. The size and shape of AuNSs can be tuned by simply adjusting the amount of added GA. Under the optimum condition, the as-prepared AuNSs with diameters about 100 nm exhibit strong near-infrared absorption, good photothermal efficiency, and high biocompatibility. We demonstrate that AuNSs can be utilized for simultaneous photoacoustic imaging and photothermal therapy in living cancer cells. This study highlights facile synthesized AuNSs could serve as a promising platform for cancer diagnosis and therapy.

  15. Biological tracer for waste site characterization

    Energy Technology Data Exchange (ETDEWEB)

    Strong-Gunderson, J.

    1995-07-01

    Remediating hazardous waste sites requires detailed site characterization. In groundwater remediation, characterizing the flow paths and velocity is a major objective. Various tracers have been used for measuring groundwater velocity and transport of contaminants, colloidal particles, and bacteria and nutrients. The conventional techniques use dissolved solutes, dyes. and gases to estimate subsurface transport pathways. These tracers can provide information on transport and diffusion into the matrix, but their estimates for groundwater flow through fractured regions are very conservative. Also, they do not have the same transport characteristics as bacteria and suspended colloid tracers, both of which must be characterized for effective in-place remediation. Bioremediation requires understanding bacterial transport and nutrient distribution throughout the acquifer, knowledge of contaminants s mobile colloidal particles is just essential.

  16. Enhanced Oil Recovery: Aqueous Flow Tracer Measurement

    Energy Technology Data Exchange (ETDEWEB)

    Joseph Rovani; John Schabron

    2009-02-01

    A low detection limit analytical method was developed to measure a suite of benzoic acid and fluorinated benzoic acid compounds intended for use as tracers for enhanced oil recovery operations. Although the new high performance liquid chromatography separation successfully measured the tracers in an aqueous matrix at low part per billion levels, the low detection limits could not be achieved in oil field water due to interference problems with the hydrocarbon-saturated water using the system's UV detector. Commercial instrument vendors were contacted in an effort to determine if mass spectrometry could be used as an alternate detection technique. The results of their work demonstrate that low part per billion analysis of the tracer compounds in oil field water could be achieved using ultra performance liquid chromatography mass spectrometry.

  17. RRR-α-tocopheryl succinate inhibits human gastric cancer SGC-7901 cell growth by inducing apoptosis and DNA synthesis arrest

    Institute of Scientific and Technical Information of China (English)

    Kun Wu; Yan Zhao; Bai-He Liu; Yao Li; Fang Liu; Jian Guo; Wei-Ping Yu

    2002-01-01

    AIM: To investigate the effects of growth inhibition ofhuman gastric cancer SGC-7901 cell with RRR-α-tocopherylsuccinate (VES), a derivative of natural Vitamin E, viainducing apoptosis and DNA synthesis arrest.METHODS: Human gastric cancer SGC-7901 cells wereregularly incubated in the presence of VES at 5, 10 and20mg@ L 1(VES was dissolved in absolute ethanol anddiluted in RPMI 1640 complete condition mediacorrespondingly to a final concentration of VES and 1mL@L-1 ethanol), succinic acid and ethanol equivalents asvehicle (VEH) control andcondition media only asuntreated (UT) control. Trypan blue dye exclusionanalysis and MTT assay were applied to detect the cellproliferation. 37kBq of tritiated thymidine was added tocells and [3H] TdR uptake was measured to observe DNAsynthesis. Apoptotic morphology was observed byelectron microscopy and DAPI staining. Flow cytometryand terminal deoxynucleotidyl transferase-mediated dUTPnick end labeling (TUNEL) assay were performed to detectVES-triggered apoptosis.RESULTS: VES inhibited SGC-7901 cell growth in a dose-dependent manner. The growth curve showed suppressionby 24.7%, 49.2% and 68.7% following 24h of VEStreatment at 5, 10 and 20 mg@L 1, respectively, similar tothe findings from MTT assay. DNA synthesis wasevidently reduced by 35%, 45% and 98% after 24h VEStreatment at 20 mg@ L-1 and 48h at 10 and 20 mg@ L 1,respectively. VES induced SGC-7901 cells to undergoapoptosis with typically apoptotic characteristics,including morphological changes of chromatincondensation, chromatin crescent formation/margination,nucleus fragmentation and apoptotic body formation,typical apoptotic sub-G1 peak by flow cytometry andincrease of apoptotic cells by TUNEL assay in which 90%of cells underwent apoptosis after 48h of VES treatment at20 mcg@L-1.CONCLUSION: VES can inhibit human gastric cancer SGC-7901 cell growth by inducing apoptosis and DNA synthesisarrest. Inhibition of SGC-7901 cell growth by VES is dose-and time

  18. Conductive polymer-based nanoparticles for laser-mediated photothermal ablation of cancer: synthesis, characterization, and in vitro evaluation

    Directory of Open Access Journals (Sweden)

    Cantu T

    2017-01-01

    Full Text Available Travis Cantu,1 Kyle Walsh,2 Varun P Pattani,3 Austin J Moy,3 James W Tunnell,3 Jennifer A Irvin,1,2 Tania Betancourt1,2 1Materials Science, Engineering, and Commercialization Program, Texas State University, San Marcos, TX, USA; 2Department of Chemistry and Biochemistry, Texas State University, San Marcos, TX, USA; 3Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX, USA Abstract: Laser-mediated photothermal ablation of cancer cells aided by photothermal agents is a promising strategy for localized, externally controlled cancer treatment. We report the synthesis, characterization, and in vitro evaluation of conductive polymeric nanoparticles (CPNPs of poly(diethyl-4,4'-{[2,5-bis(2,3-dihydrothieno[3,4-b][1,4]dioxin-5-yl-1,4-phenylene]bis(oxy}dibutanoate (P1 and poly(3,4-ethylenedioxythiophene (PEDOT stabilized with 4-dodecylbenzenesulfonic acid and poly(4-styrenesulfonic acid-co-maleic acid as photothermal ablation agents. The nanoparticles were prepared by oxidative-emulsion polymerization, yielding stable aqueous suspensions of spherical particles of <100 nm diameter as determined by dynamic light scattering and electron microscopy. Both types of nanoparticles show strong absorption of light in the near infrared region, with absorption peaks at 780 nm for P1 and 750 nm for PEDOT, as well as high photothermal conversion efficiencies (~50%, that is higher than commercially available gold-based photothermal ablation agents. The nanoparticles show significant photostability as determined by their ability to achieve consistent temperatures and to maintain their morphology upon repeated cycles of laser irradiation. In vitro studies in MDA-MB-231 breast cancer cells demonstrate the cytocompatibility of the CPNPs and their ability to mediate complete cancer cell ablation upon irradiation with an 808-nm laser, thereby establishing the potential of these systems as agents for laser-induced photothermal therapy. Keywords

  19. Geologic flow characterization using tracer techniques

    Energy Technology Data Exchange (ETDEWEB)

    Klett, R. D.; Tyner, C. E.; Hertel, Jr., E. S.

    1981-04-01

    A new tracer flow-test system has been developed for in situ characterization of geologic formations. This report describes two sets of test equipment: one portable and one for testing in deep formations. Equations are derived for in situ detector calibration, raw data reduction, and flow logging. Data analysis techniques are presented for computing porosity and permeability in unconfined isotropic media, and porosity, permeability and fracture characteristics in media with confined or unconfined two-dimensional flow. The effects of tracer pulse spreading due to divergence, dispersion, and porous formations are also included.

  20. Transformationally decoupling clustering and tracer bias

    CERN Document Server

    Neyrinck, Mark C

    2014-01-01

    Gaussianizing transformations are used statistically in many non-cosmological fields, but in cosmology, we are only starting to apply them. Here I explain a strategy of analyzing the 1-point function (PDF) of a spatial field, together with the 'essential' clustering statistics of the Gaussianized field, which are invariant to a local transformation. In cosmology, if the tracer sampling is sufficient, this achieves two important goals. First, it can greatly multiply the Fisher information, which is negligible on nonlinear scales in the usual $\\delta$ statistics. Second, it decouples clustering statistics from a local bias description for tracers such as galaxies.

  1. A review of methods for modelling environmental tracers in groundwater: Advantages of tracer concentration simulation

    Science.gov (United States)

    Turnadge, Chris; Smerdon, Brian D.

    2014-11-01

    Mathematical models of varying complexity have been developed since the 1960s to interpret environmental tracer concentrations in groundwater flow systems. This review examines published studies of model-based environmental tracer interpretation, the progress of different modelling approaches, and also considers the value of modelling tracer concentrations directly rather than estimations of groundwater age. Based on citation metrics generated using the Web of Science and Google Scholar reference databases, the most highly utilised interpretation approaches are lumped parameter models (421 citations), followed closely by direct age models (220 citations). A third approach is the use of mixing cell models (99 citations). Although lumped parameter models are conceptually simple and require limited data, they are unsuitable for characterising the internal dynamics of a hydrogeological system and/or under conditions where large scale anthropogenic stresses occur within a groundwater basin. Groundwater age modelling, and in particular, the simulation of environmental tracer transport that explicitly accounts for the accumulation and decay of tracer mass, has proven to be highly beneficial in constraining numerical models. Recent improvements in computing power have made numerical simulation of tracer transport feasible. We argue that, unlike directly simulated ages, the results of tracer mass transport simulation can be compared directly to observations, without needing to correct for apparent age bias or other confounding factors.

  2. Synthesis of 18F-c(RGDfK) as Integrin αvβ3 Targeted PET Tracer via Click Chemsitry with Cu( I ) Catalyst Systems%整合素αvβ3靶向PET探针18F-c(RGDfK)在Cu(I)催化体系中的点击合成

    Institute of Scientific and Technical Information of China (English)

    施玲丽; 李剑波; 王成; 贾丽娜; 汪勇先; 张岚

    2012-01-01

    As one of the most important types of Click chemistry, copper-catalyzed 1,3-dipolar cycloaddition reaction has attracted great attention. In this study, 2-[ l8F]fluoroethyl azide( [ 18F]FEA) was synthesized by nucleophilic substitution of 18F-. Then, [l8F]fluoroethyl-1 H-1 ,2,3-triazole-4-c(RGDfK) [18F-c(RGDfK) ] was radio-synthesized as integrin αvβ3 targeted PET tracer fast and efficiently via Click reaction of [ 18F] FEA with propioloyl c( RGDfK). Three catalyst systems of click reaction were investigated: CuS04/NaVc, Cul(s) and CuI/NH4OH, the last two have been used in peptide-click-labeling for the first time. While CuS04/NaVc catalysing the Click reaction, the total radio-chemistry yield of 18F-c( RGDfK) was 62% and the synthesis time was about 60 min(decay-corrected). Click chemistry has demonstrated to be an extraordinarily efficient and convenient method for the preparation of 18F labeled peptides.%通过2-叠氮乙基对甲苯磺酸酯的18 F-亲核取代反应,制备了[18F]2-氟叠氮乙烷,并与丙炔酸修饰的c(RGDfK)反应,采用常用的CuSO4/NaVc催化体系,并尝试了CuI(s)和CuI/NH4OH 2种催化体系,通过点击化学方法合成了整合素αvβ3靶向PET探针[18 F]氟乙基-1,4-取代1,2,3-三唑c(RGDfK)[ 18F-c(RGDfK)].在CuSO4/NaVc的催化下,18 F-c(RGDfK)的总合成时间约为60 min,总收率62%(从[18F]F-起计,经过衰变校正).实验结果表明,点击化学方法高效便捷,适于多肽的18F标记.

  3. Anti-protozoal and anti-bacterial antibiotics that inhibit protein synthesis kill cancer subtypes enriched for stem cell-like properties.

    Science.gov (United States)

    Cuyàs, Elisabet; Martin-Castillo, Begoña; Corominas-Faja, Bruna; Massaguer, Anna; Bosch-Barrera, Joaquim; Menendez, Javier A

    2015-01-01

    Key players in translational regulation such as ribosomes might represent powerful, but hitherto largely unexplored, targets to eliminate drug-refractory cancer stem cells (CSCs). A recent study by the Lisanti group has documented how puromycin, an old antibiotic derived from Streptomyces alboniger that inhibits ribosomal protein translation, can efficiently suppress CSC states in tumorspheres and monolayer cultures. We have used a closely related approach based on Biolog Phenotype Microarrays (PM), which contain tens of lyophilized antimicrobial drugs, to assess the chemosensitivity profiles of breast cancer cell lines enriched for stem cell-like properties. Antibiotics directly targeting active sites of the ribosome including emetine, puromycin and cycloheximide, inhibitors of ribosome biogenesis such as dactinomycin, ribotoxic stress agents such as daunorubicin, and indirect inhibitors of protein synthesis such as acriflavine, had the largest cytotoxic impact against claudin-low and basal-like breast cancer cells. Thus, biologically aggressive, treatment-resistant breast cancer subtypes enriched for stem cell-like properties exhibit exacerbated chemosensitivities to anti-protozoal and anti-bacterial antibiotics targeting protein synthesis. These results suggest that old/existing microbicides might be repurposed not only as new cancer therapeutics, but also might provide the tools and molecular understanding needed to develop second-generation inhibitors of ribosomal translation to eradicate CSC traits in tumor tissues.

  4. Anti-protozoal and anti-bacterial antibiotics that inhibit protein synthesis kill cancer subtypes enriched for stem cell-like properties

    Science.gov (United States)

    Cuyàs, Elisabet; Martin-Castillo, Begoña; Corominas-Faja, Bruna; Massaguer, Anna; Bosch-Barrera, Joaquim; Menendez, Javier A

    2015-01-01

    Key players in translational regulation such as ribosomes might represent powerful, but hitherto largely unexplored, targets to eliminate drug-refractory cancer stem cells (CSCs). A recent study by the Lisanti group has documented how puromycin, an old antibiotic derived from Streptomyces alboniger that inhibits ribosomal protein translation, can efficiently suppress CSC states in tumorspheres and monolayer cultures. We have used a closely related approach based on Biolog Phenotype Microarrays (PM), which contain tens of lyophilized antimicrobial drugs, to assess the chemosensitivity profiles of breast cancer cell lines enriched for stem cell-like properties. Antibiotics directly targeting active sites of the ribosome including emetine, puromycin and cycloheximide, inhibitors of ribosome biogenesis such as dactinomycin, ribotoxic stress agents such as daunorubicin, and indirect inhibitors of protein synthesis such as acriflavine, had the largest cytotoxic impact against claudin-low and basal-like breast cancer cells. Thus, biologically aggressive, treatment-resistant breast cancer subtypes enriched for stem cell-like properties exhibit exacerbated chemosensitivities to anti-protozoal and anti-bacterial antibiotics targeting protein synthesis. These results suggest that old/existing microbicides might be repurposed not only as new cancer therapeutics, but also might provide the tools and molecular understanding needed to develop second-generation inhibitors of ribosomal translation to eradicate CSC traits in tumor tissues. PMID:25970790

  5. Methotrexate-conjugated quantum dots: synthesis, characterisation and cytotoxicity in drug resistant cancer cells.

    Science.gov (United States)

    Johari-Ahar, Mohammad; Barar, Jaleh; Alizadeh, Ali Mohammad; Davaran, Soodabeh; Omidi, Yadollah; Rashidi, Mohammad-Reza

    2016-01-01

    Methotrexate (MTX), a folic acid derivative, is a potent anticancer used for treatment of different malignancies, but possible initiation of drug resistance to MTX by cancer cells has limited its applications. Nanoconjugates (NCs) of MTX to quantum dots (QDs) may favour the cellular uptake via folate receptors (FRs)-mediated endocytosis that circumvents the efflux functions of cancer cells. We synthesised MTX-conjugated l-cysteine capped CdSe QDs (MTX-QD nanoconjugates) and evaluated their internalisation and cytotoxicity in the KB cells with/without resistancy to MTX. The NCs were fully characterised by high resolution transmission electron microscopy (HR-TEM), atomic force microscopy (AFM), dynamic light scattering (DLS) and optical spectroscopy. Upon conjugation with MTX, the photoluminescence (PL) properties of QDs altered, while an obvious quenching in PL of QDs was observed after physical mixing. The MTX-QD nanoconjugates efficiently internalised into the cancer cells, and induced markedly high cytotoxicity (IC50, 12.0 µg/mL) in the MTX-resistant KB cells as compared to the free MTX molecules (IC50,105.0 µg/mL), whereas, these values were respectively about 7.0 and 0.6 µg/mL in the MTX-sensitive KB cells. Based on these findings, the MTX-QD nanoconjugates are proposed for the targeted therapy of MTX-resistant cancers, which may provide an improved outcome in the relapsed FR-overexpressing cancers.

  6. Design, synthesis, and computational studies on dihydropyrimidine scaffolds as potential lipoxygenase inhibitors and cancer chemopreventive agents.

    Science.gov (United States)

    Venugopala, Katharigatta N; Govender, Reshme; Khedr, Mohammed A; Venugopala, Rashmi; Aldhubiab, Bandar E; Harsha, Sree; Odhav, Bharti

    2015-01-01

    Dihydropyrimidine scaffold has a wide range of potential pharmacological activities such as antiviral, antitubercular, antimalarial, anti-inflammatory, and anticancer properties. 5-Lipoxygenase enzyme is an enzyme responsible for the metabolism of arachidonic acid to leukotrienes. The elevated levels of this enzyme and its metabolites in cancer cells have a direct relation on the development of cancer when compared to normal cells. The development of novel lipoxygenase inhibitors can have a major role in cancer therapy. A series of substituted 1,4-dihydropyrimidine analogues were synthesized and characterized by (1)H-NMR, (13)C-NMR, and HRMS. Molecular docking against lipoxygenase enzyme (protein data bank code =3V99) was done using Molecular Operating Environment 2013.08 and Leadit 2.1.2 softwares and showed high affinities. The synthesized compounds were tested for their lipoxygenase inhibitory activity and showed inhibition ranging from 59.37%±0.66% to 81.19%±0.94%. The activity was explained by a molecular docking study. The title compounds were also tested for cytotoxic activity against two human cancer cell lines Michigan Cancer Foundation-7 and human melanoma cells and a normal peripheral blood mononuclear cell line.

  7. Developing Inhibitors of Translesion DNA Synthesis as Therapeutic Agents Against Lung Cancer

    Science.gov (United States)

    2014-10-01

    nuclear magnetic resonance ( NMR spectroscopy (Figure 3). Figure 2. Mass spectroscopy to verify the molecular weight of 3-ethynyl-5-nitroindolyl-2...8217 -deoxynucleoside. 0 20 25 mia Figure 3. NMR spectrum of 3-ethynyl-5-nitroindolyl- 2’ -deoxynucleoside. ~~. A-::.~, C-*!&t:.,. I As described...provided in Figure 2D . The kinetic parameters for pol  during normal and translesion DNA synthesis are summarized in Table 1. These data indicate

  8. Biscoumarin derivatives: Synthesis, crystal structure, theoretical studies and induced apoptosis activity on bladder urothelial cancer cell

    Science.gov (United States)

    Xin, Jia-jia; Li, Jing; Zhang, Zi-dan; Hu, Xing-bin; Li, Ming-kai

    2015-03-01

    In this study, five new biscoumarin derivatives (1-5) were synthesized and compound 4 inhibited the proliferation of the bladder urothelial cells (J82 cell line) obviously after 48 h treatment at different concentration (1, 5 and 10 μmol/L), and J82 cells were predominantly induced to apoptotic cell death after compound 4 treatment. Morphologic changes of bladder urothelial cancer cells were also observed under transmission electron microscopy (TEM) after compound 4 treatment. In addition, compound 4 had much less toxicity to human umbilical vein endothelial cells. To explore the possible anti-cancer mechanism of compound 4, two classical intramolecular Osbnd H⋯O hydrogen bonds (HBs) in their structures and the corresponding HB energies were performed with the density functional theory (DFT) [B3LYP/6-31G∗] method. Anti-bladder cancer activity of compound 4 is possible due to the intramolecular weakest HB energies.

  9. Synthesis of Chromonylthiazolidines and Their Cytotoxicity to Human Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Hoang Le Tuan Anh

    2015-01-01

    Full Text Available Nine new chromonylthiazolidine derivatives were successfully semi-synthesized from paeonol. All of the compounds, including starting materials, the intermediate compound and products, were evaluated for their cytotoxic effects toward eight human cancer cell lines. The synthesized chromonylthiazolidines displayed weak cytotoxic effects against the tested cancer cell lines, but selective cytotoxic effects were observed. Compounds 3a and 3b showed the most selective cytotoxic effects against human epidermoid carcinoma (IC50 44.1 ± 3.6 μg/mL and breast cancer (IC50 32.8 ± 1.4 μg/mL cell lines, respectively. The results suggest that chromoylthiazolidines are potential low-cost, and selective anticancer agents.

  10. Synthesis and anti-cancer activity of naturally occurring 2,5-diketopiperazines.

    Science.gov (United States)

    Mollica, Adriano; Costante, Roberto; Fiorito, Serena; Genovese, Salvatore; Stefanucci, Azzurra; Mathieu, Veronique; Kiss, Robert; Epifano, Francesco

    2014-10-01

    Three naturally occurring oxyprenylated diketopiperazines were synthesized and preliminarily tested as growth inhibitory agents in vitro against various cancer cell lines. The compounds were tested on six human cancer cell lines with different sensitivity to proapoptotic stimuli using the MTT colorimetric assay. The data revealed that of the chemicals under study only deoxymicelianamide (11) displayed the highest activity, recording mean IC50 growth inhibitory values ranging from 2 to 23 μM. A comparative study with the non-geranylated saturated derivative of (11) revealed the importance of the presence of the geranyloxy side chain and the exocyclic 2,5-DPK double bond moiety for the observed activity.

  11. Metformin inhibition of mTORC1 activation, DNA synthesis and proliferation in pancreatic cancer cells: Dependence on glucose concentration and role of AMPK

    Energy Technology Data Exchange (ETDEWEB)

    Sinnett-Smith, James; Kisfalvi, Krisztina; Kui, Robert [Division of Digestive Diseases, Department of Medicine, CURE: Digestive Diseases Research Center, David Geffen School of Medicine and Molecular Biology Institute, University of California at Los Angeles, CA (United States); Rozengurt, Enrique, E-mail: erozengurt@mednet.ucla.edu [Division of Digestive Diseases, Department of Medicine, CURE: Digestive Diseases Research Center, David Geffen School of Medicine and Molecular Biology Institute, University of California at Los Angeles, CA (United States)

    2013-01-04

    Highlights: Black-Right-Pointing-Pointer Metformin inhibits cancer cell growth but the mechanism(s) are not understood. Black-Right-Pointing-Pointer We show that the potency of metformin is sharply dependent on glucose in the medium. Black-Right-Pointing-Pointer AMPK activation was enhanced in cancer cells incubated in physiological glucose. Black-Right-Pointing-Pointer Reciprocally, metformin potently inhibited mTORC1, DNA synthesis and proliferation. Black-Right-Pointing-Pointer Metformin, at low concentrations, inhibited DNA synthesis through AMPK. -- Abstract: Metformin, a widely used anti-diabetic drug, is emerging as a potential anticancer agent but the mechanisms involved remain incompletely understood. Here, we demonstrate that the potency of metformin induced AMPK activation, as shown by the phosphorylation of its substrates acetyl-CoA carboxylase (ACC) at Ser{sup 79} and Raptor at Ser{sup 792}, was dramatically enhanced in human pancreatic ductal adenocarcinoma (PDAC) cells PANC-1 and MiaPaCa-2 cultured in medium containing physiological concentrations of glucose (5 mM), as compared with parallel cultures in medium with glucose at 25 mM. In physiological glucose, metformin inhibited mTORC1 activation, DNA synthesis and proliferation of PDAC cells stimulated by crosstalk between G protein-coupled receptors and insulin/IGF signaling systems, at concentrations (0.05-0.1 mM) that were 10-100-fold lower than those used in most previous reports. Using siRNA-mediated knockdown of the {alpha}{sub 1} and {alpha}{sub 2} catalytic subunits of AMPK, we demonstrated that metformin, at low concentrations, inhibited DNA synthesis through an AMPK-dependent mechanism. Our results emphasize the importance of using medium containing physiological concentrations of glucose to elucidate the anticancer mechanism of action of metformin in pancreatic cancer cells and other cancer cell types.

  12. Heme-iron complexing biphenyl and naphthalene derivatives as CYP17 inhibitorsfor the treatment of prostate cancer : design, synthesis and evaluation

    OpenAIRE

    Pinto-Bazurco Mendieta, Mariano Aurelio Ernesto

    2009-01-01

    Insufficient efficacy and unsafe treatment options are the current state of the art of prostate cancer therapies. This motivated us to develop antiandrogenic drugs with reduced side effects, aiming at effective tumor growth prevention and regression for prostatic adenocarcinomas. The key enzyme in androgen synthesis CYP17 is to date the most promising target for an overall, mild treatment of prostate carcinomas. Thus, it was our aim to develop nonsteroidal CYP17 inhibitors. In the present wor...

  13. Travel-time-based thermal tracer tomography

    Science.gov (United States)

    Somogyvári, Márk; Bayer, Peter; Brauchler, Ralf

    2016-05-01

    Active thermal tracer testing is a technique to get information about the flow and transport properties of an aquifer. In this paper we propose an innovative methodology using active thermal tracers in a tomographic setup to reconstruct cross-well hydraulic conductivity profiles. This is facilitated by assuming that the propagation of the injected thermal tracer is mainly controlled by advection. To reduce the effects of density and viscosity changes and thermal diffusion, early-time diagnostics are used and specific travel times of the tracer breakthrough curves are extracted. These travel times are inverted with an eikonal solver using the staggered grid method to reduce constraints from the pre-defined grid geometry and to improve the resolution. Finally, non-reliable pixels are removed from the derived hydraulic conductivity tomograms. The method is applied to successfully reconstruct cross-well profiles as well as a 3-D block of a high-resolution fluvio-aeolian aquifer analog data set. Sensitivity analysis reveals a negligible role of the injection temperature, but more attention has to be drawn to other technical parameters such as the injection rate. This is investigated in more detail through model-based testing using diverse hydraulic and thermal conditions in order to delineate the feasible range of applications for the new tomographic approach.

  14. Using neural networks to describe tracer correlations

    Directory of Open Access Journals (Sweden)

    D. J. Lary

    2004-01-01

    Full Text Available Neural networks are ideally suited to describe the spatial and temporal dependence of tracer-tracer correlations. The neural network performs well even in regions where the correlations are less compact and normally a family of correlation curves would be required. For example, the CH4-N2O correlation can be well described using a neural network trained with the latitude, pressure, time of year, and methane volume mixing ratio (v.m.r.. In this study a neural network using Quickprop learning and one hidden layer with eight nodes was able to reproduce the CH4-N2O correlation with a correlation coefficient between simulated and training values of 0.9995. Such an accurate representation of tracer-tracer correlations allows more use to be made of long-term datasets to constrain chemical models. Such as the dataset from the Halogen Occultation Experiment (HALOE which has continuously observed CH4  (but not N2O from 1991 till the present. The neural network Fortran code used is available for download.

  15. Nanoparticle tracers in calcium carbonate porous media

    KAUST Repository

    Li, Yan Vivian

    2014-07-15

    Tracers are perhaps the most direct way of diagnosing subsurface fluid flow pathways for ground water decontamination and for natural gas and oil production. Nanoparticle tracers could be particularly effective because they do not diffuse away from the fractures or channels where flow occurs and thus take much less time to travel between two points. In combination with a chemical tracer they can measure the degree of flow concentration. A prerequisite for tracer applications is that the particles are not retained in the porous media as the result of aggregation or sticking to mineral surfaces. By screening eight nanoparticles (3-100 nm in diameter) for retention when passed through calcium carbonate packed laboratory columns in artificial oil field brine solutions of variable ionic strength we show that the nanoparticles with the least retention are 3 nm in diameter, nearly uncharged, and decorated with highly hydrophilic polymeric ligands. The details of these column experiments and the tri-modal distribution of zeta potential of the calcite sand particles in the brine used in our tests suggests that parts of the calcite surface have positive zeta potential and the retention of negatively charged nanoparticles occurs at these sites. Only neutral nanoparticles are immune to at least some retention. © 2014 Springer Science+Business Media.

  16. Fractal tracer distributions in turbulent field theories

    DEFF Research Database (Denmark)

    Hansen, J. Lundbek; Bohr, Tomas

    1998-01-01

    We study the motion of passive tracers in a two-dimensional turbulent velocity field generated by the Kuramoto-Sivashinsky equation. By varying the direction of the velocity-vector with respect to the field-gradient we can continuously vary the two Lyapunov exponents for the particle motion and t...

  17. Blood tracer kinetics in the arterial tree.

    Directory of Open Access Journals (Sweden)

    Elias Kellner

    Full Text Available Evaluation of blood supply of different organs relies on labeling blood with a suitable tracer. The tracer kinetics is linear: Tracer concentration at an observation site is a linear response to an input somewhere upstream the arterial flow. The corresponding impulse response functions are currently treated empirically without incorporating the relation to the vascular morphology of an organ. In this work we address this relation for the first time. We demonstrate that the form of the response function in the entire arterial tree is reduced to that of individual vessel segments under approximation of good blood mixing at vessel bifurcations. The resulting expression simplifies significantly when the geometric scaling of the vascular tree is taken into account. This suggests a new way to access the vascular morphology in vivo using experimentally determined response functions. However, it is an ill-posed inverse problem as demonstrated by an example using measured arterial spin labeling in large brain arteries. We further analyze transport in individual vessel segments and demonstrate that experimentally accessible tracer concentration in vessel segments depends on the measurement principle. Explicit expressions for the response functions are obtained for the major middle part of the arterial tree in which the blood flow in individual vessel segments can be treated as laminar. When applied to the analysis of regional cerebral blood flow measurements for which the necessary arterial input is evaluated in the carotid arteries, present theory predicts about 20% underestimation, which is in agreement with recent experimental data.

  18. Blood tracer kinetics in the arterial tree.

    Science.gov (United States)

    Kellner, Elias; Gall, Peter; Günther, Matthias; Reisert, Marco; Mader, Irina; Fleysher, Roman; Kiselev, Valerij G

    2014-01-01

    Evaluation of blood supply of different organs relies on labeling blood with a suitable tracer. The tracer kinetics is linear: Tracer concentration at an observation site is a linear response to an input somewhere upstream the arterial flow. The corresponding impulse response functions are currently treated empirically without incorporating the relation to the vascular morphology of an organ. In this work we address this relation for the first time. We demonstrate that the form of the response function in the entire arterial tree is reduced to that of individual vessel segments under approximation of good blood mixing at vessel bifurcations. The resulting expression simplifies significantly when the geometric scaling of the vascular tree is taken into account. This suggests a new way to access the vascular morphology in vivo using experimentally determined response functions. However, it is an ill-posed inverse problem as demonstrated by an example using measured arterial spin labeling in large brain arteries. We further analyze transport in individual vessel segments and demonstrate that experimentally accessible tracer concentration in vessel segments depends on the measurement principle. Explicit expressions for the response functions are obtained for the major middle part of the arterial tree in which the blood flow in individual vessel segments can be treated as laminar. When applied to the analysis of regional cerebral blood flow measurements for which the necessary arterial input is evaluated in the carotid arteries, present theory predicts about 20% underestimation, which is in agreement with recent experimental data.

  19. Suitability of tracers; Eignung von Tracern

    Energy Technology Data Exchange (ETDEWEB)

    Klotz, D. [GSF - Forschungszentrum fuer Umwelt und Gesundheit GmbH, Neuherberg (Germany). Inst. fuer Hydrologie

    1999-02-01

    Hydrological tracer techniques are a means of making statements on the direction and speed of underground water. One of the simpler tasks is to find out whether there is hydrological communication between two given points. This requires a determination of the direction of flow, which places less exacting demands on the properties of the tracer than does the task of determining the flow velocity of underground water. Tracer methods can serve to infer from flow velocity the distance (flow) velocity, which is defined as the ratio between the distance between two points located in flow direction and the actual time it takes water to flow from one to the other. [Deutsch] Mit Hilfe der hydrologischen Markierungstechniken koennen Aussagen ueber die Richtung und die Geschwindigkeit von Bewegungen des unterirdischen Wassers gemacht werden. Der einfachere Fall liegt vor, wenn festgestellt werden soll, ob zwischen zwei Punkten eine hydrologische Verbindung besteht. Bei dieser Fliessrichtungsbestimmung sind die Forderungen an die Eigenschaften der einzusetzenden Tracer geringer als bei der Bestimmung der Geschwindigkeit des unterirdischen Wassers. Von den Geschwindigkeiten des unterirdischen Wassers ist die Abstands-(Fliess)geschwindigkeit, die definiert ist durch das Verhaeltnis aus dem Abstand und der wahren Fliesszeit zwischen zwei in Bewegungsrichtung gelegenen Punkten, durch Tracermethoden zu bestimmen. (orig.)

  20. Cancer Survivors’ Experience With Telehealth: A Systematic Review and Thematic Synthesis

    Science.gov (United States)

    Lucas, Grace; Marcu, Afrodita; Piano, Marianne; Grosvenor, Wendy; Mold, Freda; Maguire, Roma; Ream, Emma

    2017-01-01

    Background Net survival rates of cancer are increasing worldwide, placing a strain on health service provision. There is a drive to transfer the care of cancer survivors—individuals living with and beyond cancer—to the community and encourage them to play an active role in their own care. Telehealth, the use of technology in remote exchange of data and communication between patients and health care professionals (HCPs), is an important contributor to this evolving model of care. Telehealth interventions are “complex,” and understanding patient experiences of them is important in evaluating their impact. However, a wider view of patient experience is lacking as qualitative studies detailing cancer survivor engagement with telehealth are yet to be synthesized. Objective To systematically identify, appraise, and synthesize qualitative research evidence on the experiences of adult cancer survivors participating in telehealth interventions, to characterize the patient experience of telehealth interventions for this group. Methods Medline (PubMed), PsychINFO, Cumulative Index for Nursing and Allied Health Professionals (CINAHL), Embase, and Cochrane Central Register of Controlled Trials were searched on August 14, 2015, and March 8, 2016, for English-language papers published between 2006 and 2016. Inclusion criteria were as follows: adult cancer survivors aged 18 years and over, cancer diagnosis, experience of participating in a telehealth intervention (defined as remote communication or remote monitoring with an HCP delivered by telephone, Internet, or hand-held or mobile technology), and reporting qualitative data including verbatim quotes. An adapted Critical Appraisal Skill Programme (CASP) checklist for qualitative research was used to assess paper quality. The results section of each included article was coded line by line, and all papers underwent inductive analysis, involving comparison, reexamination, and grouping of codes to develop descriptive themes

  1. Application Value of Methylene Blue Tracer in Sentinel Lymph Node Biopsy in Breast Cancer%亚甲蓝示踪法在乳腺癌前哨淋巴结活检中的应用价值分析

    Institute of Scientific and Technical Information of China (English)

    丁贵坡

    2016-01-01

    Objective To investigate the value of methylene blue in sentinel lymph node biopsy for breast cancer.Methods 125 cases of breast cancer in our hospital were selected as the research object,injected 1%methylene blue injection into the tumor or breast tissue,and then taken sentinel lymph node biopsy and axillary lymph node dissection,analyzed the rate of sentinel lymph node detection,accuracy,sensitivity and false negative.Results The operation of all cases were successful,and there were no adverse reactions and complications after operation.The detection rate of sentinel lymph nodes was 93.6%,the accuracy rate was 92%,the sensitivity was 87.3%,and the false negative rate was 14.5%.Conclusion Methylene blue has important value in sentinel lymph node biopsy for breast cancer.%目的探讨亚甲蓝示踪法在乳腺癌前哨淋巴结活检中的应用价值。方法选取我院确诊收治的125例乳腺癌患者作为研究对象,选择1%亚甲蓝注射液作为示踪剂,注射于肿瘤周围或乳腺组织内,然后行前哨淋巴结活检术和腋窝淋巴结清扫术,分析前哨淋巴结检出率、准确率、敏感度及假阴性率。结果本组125例患者手术均取得成功,术后未出现不良反应和并发症。前哨淋巴结检出率为93.6%,准确率为92.0%,敏感度为87.3%,假阴性率为14.5%。结论亚甲蓝示踪法在乳腺癌前哨淋巴结活检中具有重要的价值。

  2. Tracer injection techniques in flowing surface water

    Science.gov (United States)

    Wörman, A.

    2009-04-01

    Residence time distributions for flowing water and reactive matter are commonly used integrated properties of the transport process for determining technical issues of water resource management and in eco-hydrological science. Two general issues for tracer techniques are that the concentration-vs-time relation following a tracer injection (the breakthrough curve) gives unique transport information in different parts of the curve and separation of hydromechanical and reactive mechanisms often require simultaneous tracer injections. This presentation discusses evaluation methods for simultaneous tracer injections based on examples of tracer experiments in small rivers, streams and wetlands. Tritiated water is used as a practically inert substance to reflect the actual hydrodynamics, but other involved tracers are Cr(III)-51, P-32 and N-15. Hydromechanical, in-stream dispersion is reflected as a symmetrical spreading of the spatial concentration distribution. This requires that the transport distance over water depth is larger than about five times the flow Peclet number. Transversal retention of both inert and reactive solutes is reflected in terms of the tail of the breakthrough curve. Especially, reactive solutes can have a substantial magnification of the tailing behaviour depending on reaction rates or partitioning coefficients. To accurately discriminate between the effects of reactions and hydromechanical mixing its is relevant to use simultaneous injections of inert and reactive tracers with a sequential or integrated evaluation procedure. As an example, the slope of the P-32 tailing is consistently smaller than that of a simultaneous tritium injection in Ekeby wetland, Eskilstuna. The same applies to N-15 injected in the same experiment, but nitrogen is affected also by a systematic loss due to denitrification. Uptake in stream-bed sediments can be caused by a pumping effect arising when a variable pressure field is created on the stream bottom due to bed

  3. 单用亚甲蓝示踪剂行乳腺癌前哨淋巴结活检术(附47例报告)%Methylene Blue as Single Tracer for Sentinel Lymph Node Biopsy in Breast Cancer(a report of 4 7 cases)

    Institute of Scientific and Technical Information of China (English)

    周文斌; 麦玉嫦; 周冬仙; 钟才能; 许楠

    2014-01-01

    目的探讨单用亚甲蓝示踪剂在乳腺癌前哨淋巴结活检术(SLNB)中的临床应用效果。方法回顾性分析2010年7月至2012年6月年本科室收治的47例临床腋窝淋巴结阴性乳腺癌采用单用亚甲蓝示踪剂行 SLNB及腋窝淋巴结清扫术(ALND)的临床资料。结果47例患者中46例成功施行 SLNB,成功率97.8%;在前30例的学习曲线阶段,30例中有6例前哨淋巴结有癌转移,转移率20%;与 ALND术后结果比较,SLNB准确率100%,假阴性率0%。与行 ALND患者比较,行 SLNB患者术后患肢淋巴水肿、肩部不适、肩关节活动障碍等不良事件发生率明显降低。结论在规范操作的前提下,单用亚甲蓝示踪剂行乳腺癌 SL-NB简单可行、安全有效、可获得良好的成功率和准确率。%Obj ective]To explore the clinical efficacy of methylene blue as single tracer for sentinel lymph node biopsy(SLNB)in breast cancer.[Methods]Clinical data of 47 patients with clinical axillary lymph node-negative breast cancer undergoing SLNB and axillary lymph node dissection(ALND)in our department from July 2010 to June 2012 were analyzed retrospectively.[Results]Among 47 patients,46 patients underwent SLNB successfully,and the success rate was 97.8%.During the learning curve period of 30 patients,6 pa-tients had sentinel lymph node metastases,and the metastasis rate was 20%.Compared with the outcomes of ALND,the accuracy and false negative rate of SLNB were 100% and 0%,respectively.Compared with pa-tients undergoing ALND,the incidence rates of lymphedema of diseased limbs,shoulder discomfort,shoulder joint movement disorder and so on in patients undergoing SLNB were obviously reduced.[Conclusion]Based on the standard operation,methylene blue as single tracer for SLNB in breast cancer is simple,feasible,safe and effective,and can obtain good success rate and accuracy rate.

  4. Halon-1301, a new Groundwater Age Tracer

    Science.gov (United States)

    Beyer, Monique; van der Raaij, Rob; Morgenstern, Uwe; Jackson, Bethanna

    2015-04-01

    Groundwater dating is an important tool to assess groundwater resources in regards to direction and time scale of groundwater flow and recharge and to assess contamination risks and manage remediation. To infer groundwater age information, a combination of different environmental tracers, such as tritium and SF6, are commonly used. However ambiguous age interpretations are often faced, due to a limited set of available tracers and limitations of each tracer method when applied alone. There is a need for additional, complementary groundwater age tracers. We recently discovered that Halon-1301, a water soluble and entirely anthropogenic gaseous substance, may be a promising candidate [Beyer et al, 2014]. Halon-1301 can be determined along with SF6, SF5CF3 and CFC-12 in groundwater using a gas chromatography setup with attached electron capture detector developed by Busenberg and Plummer [2008]. Halon-1301 has not been assessed in groundwater. This study assesses the behaviour of Halon-1301 in water and its suitability as a groundwater age tracer. We determined Halon-1301 in 17 groundwater and various modern (river) waters sites located in 3 different groundwater systems in the Wellington Region, New Zealand. These waters have been previously dated with tritium, CFC-12, CFC-11 and SF6 with mean residence times ranging from 0.5 to over 100 years. The waters range from oxic to anoxic and some show evidence of CFC contamination or degradation. This allows us to assess the different properties affecting the suitability of Halon-1301 as groundwater age tracer, such as its conservativeness in water and local contamination potential. The samples are analysed for Halon-1301 and SF6simultaneously, which allows identification of issues commonly faced when using gaseous tracers such as contamination with modern air during sampling. Overall we found in the assessed groundwater samples Halon-1301 is a feasible new groundwater tracer. No sample indicated significantly elevated

  5. Design, synthesis, and in vitro and in vivo biological studies of a 3'-deoxythymidine conjugate that potentially kills cancer cells selectively.

    Directory of Open Access Journals (Sweden)

    Qiong Wei

    Full Text Available Thymidine kinases (TKs have been considered one of the potential targets for anticancer therapeutic because of their elevated expressions in cancer cells. However, nucleobase analogs targeting TKs have shown poor selective cytotoxicity in cancer cells despite effective antiviral activity. 3'-Deoxythymidine phenylquinoxaline conjugate (dT-QX was designed as a novel nucleobase analog to target TKs in cancer cells and block cell replication via conjugated DNA intercalating quinoxaline moiety. In vitro cell screening showed that dT-QX selectively kills a variety of cancer cells including liver carcinoma, breast adenocarcinoma and brain glioma cells; whereas it had a low cytotoxicity in normal cells such as normal human liver cells. The anticancer activity of dT-QX was attributed to its selective inhibition of DNA synthesis resulting in extensive mitochondrial superoxide stress in cancer cells. We demonstrate that covalent linkage with 3'-deoxythymidine uniquely directed cytotoxic phenylquinoxaline moiety more toward cancer cells than normal cells. Preliminary mouse study with subcutaneous liver tumor model showed that dT-QX effectively inhibited the growth of tumors. dT-QX is the first molecule of its kind with highly amendable constituents that exhibits this selective cytotoxicity in cancer cells.

  6. One-pot one-cluster synthesis of fluorescent and bio-compatible Ag14 nanoclusters for cancer cell imaging

    Science.gov (United States)

    Yang, Jie; Xia, Nan; Wang, Xinan; Liu, Xianhu; Xu, An; Wu, Zhikun; Luo, Zhixun

    2015-11-01

    Small-molecule-protected silver nanoclusters have smaller hydrodynamic diameter, and thus may hold greater potential in biomedicine application compared with the same core-sized, macromolecule (i.e. DNA)-protected silver nanoclusters. However, the live cell imaging labeled by small-molecule-protected silver nanoclusters has not been reported until now, and the synthesis and atom-precise characterization of silver nanoclusters have been challenging for a long time. We develop a one-pot one-cluster synthesis method to prepare silver nanoclusters capped with GSH which is bio-compatible. The as-prepared silver nanoclusters are identified to be Ag14(SG)11 (abbreviated as Ag14, SG: glutathione) by isotope-resolvable ESI-MS. The structure is probed by 1D NMR spectroscopy together with 2D COSY and HSQC. This cluster species is fluorescent and the fluorescence quantum yield is solvent-dependent. Very importantly, Ag14 was successfully applied to label lung cancer cells (A549) for imaging, and this work represents the first attempt to image live cells with small-molecule-protected silver nanoclusters. Furthermore, it is revealed that the Ag14 nanoclusters exhibit lower cytotoxicity compared with some other silver species (including silver salt, silver complex and large silver nanoparticles), and the explanation is also provided. The comparison of silver nanoclusters to state-of-the-art labeling materials in terms of cytotoxicity and photobleaching lifetime is also conducted.Small-molecule-protected silver nanoclusters have smaller hydrodynamic diameter, and thus may hold greater potential in biomedicine application compared with the same core-sized, macromolecule (i.e. DNA)-protected silver nanoclusters. However, the live cell imaging labeled by small-molecule-protected silver nanoclusters has not been reported until now, and the synthesis and atom-precise characterization of silver nanoclusters have been challenging for a long time. We develop a one-pot one

  7. Synthesis and Biological Evaluation of Retinoid-Chalcones as Inhibitors of Colon Cancer Cell Growth

    Science.gov (United States)

    Based on the observed anticancer activity of chalcones and retinoids, a novel class of retinoid-chalcone hybrids were designed and synthesized. As part of our ongoing studies to discover natural product based anticancer compounds, the retinoid-chalcone hybrids were tested against the colon cancer ce...

  8. Laplace transform in tracer kinetic modeling

    Energy Technology Data Exchange (ETDEWEB)

    Hauser, Eliete B., E-mail: eliete@pucrs.br [Instituto do Cerebro (InsCer/FAMAT/PUC-RS), Porto Alegre, RS, (Brazil). Faculdade de Matematica

    2013-07-01

    The main objective this paper is to quantify the pharmacokinetic processes: absorption, distribution and elimination of radiopharmaceutical(tracer), using Laplace transform method. When the drug is administered intravenously absorption is complete and is available in the bloodstream to be distributed throughout the whole body in all tissues and fluids, and to be eliminated. Mathematical modeling seeks to describe the processes of distribution and elimination through compartments, where distinct pools of tracer (spatial location or chemical state) are assigned to different compartments. A compartment model is described by a system of differential equations, where each equation represents the sum of all the transfer rates to and from a specific compartment. In this work a two-tissue irreversible compartment model is used for description of tracer, [{sup 18}F]2-fluor-2deoxy-D-glucose. In order to determine the parameters of the model, it is necessary to have information about the tracer delivery in the form of an input function representing the time-course of tracer concentration in arterial blood or plasma. We estimate the arterial input function in two stages and apply the Levenberg-Marquardt Method to solve nonlinear regressions. The transport of FDG across de arterial blood is very fast in the first ten minutes and then decreases slowly. We use de Heaviside function to represent this situation and this is the main contribution of this study. We apply the Laplace transform and the analytical solution for two-tissue irreversible compartment model is obtained. The only approach is to determinate de arterial input function. (author)

  9. Photothermal cancer therapy using graphitic carbon–coated magnetic particles prepared by one-pot synthesis

    Directory of Open Access Journals (Sweden)

    Lee HJ

    2014-12-01

    Full Text Available Hyo-Jeong Lee,1 Jakkid Sanetuntikul,2 Eun-Sook Choi,1 Bo Ram Lee,1 Jung-Hee Kim,1 Eunjoo Kim,1 Sangaraju Shanmugam2 1Nano and Bio Research Division, 2Department of Energy Systems Engineering, Daegu Gyeongbuk Institute of Science and Technology, Daegu, Republic of Korea Abstract: We describe here a simple synthetic strategy for the fabrication of carbon-coated Fe3O4 (Fe3O4@C particles using a single-component precursor, iron (III diethylenetriaminepentaacetic acid complex. Physicochemical analyses revealed that the core of the synthesized particles consists of ferromagnetic Fe3O4 material ranging several hundred nanometers, embedded in nitrogen-doped graphitic carbon with a thickness of ~120 nm. Because of their photothermal activity (absorption of near-infrared [NIR] light, the Fe3O4@C particles have been investigated for photothermal therapeutic applications. An example of one such application would be the use of Fe3O4@C particles in human adenocarcinoma A549 cells by means of NIR-triggered cell death. In this system, the Fe3O4@C can rapidly generate heat, causing >98% cell death within 10 minutes under 808 nm NIR laser irradiation (2.3 W cm-2. These Fe3O4@C particles provided a superior photothermal therapeutic effect by intratumoral delivery and NIR irradiation of tumor xenografts. These results demonstrate that one-pot synthesis of carbon-coated magnetic particles could provide promising materials for future clinical applications and encourage further investigation of this simple method. Keywords: graphitic carbon–encapsulated magnetic nanoparticles, iron oxide, one-pot synthesis, photothermal cancer therapy

  10. Combinatorial synthesis and screening of cancer cell-specific nanomedicines targeted via phage fusion proteins

    Directory of Open Access Journals (Sweden)

    James W. Gillespie

    2015-06-01

    Full Text Available Active tumor targeting of nanomedicines has recently shown significant improvements in the therapeutic activity of currently existing drug delivery systems, such as liposomal doxorubicin (Doxil/Caelyx/Lipodox. Previously, we have shown that isolated pVIII major coat proteins of the fd tet filamentous phage vector, containing cancer cell-specific peptide fusions at their N terminus, can be used as active targeting ligands in a liposomal doxorubicin delivery system in vitro and in vivo. Here, we show a novel major coat protein isolation procedure in 2-propanol that allows spontaneous incorporation of the hydrophobic protein core into preformed liposomal doxorubicin with minimal damage or drug loss while still retaining the targeting ligand exposed for cell-specific targeting. Using a panel of 12 structurally unique ligands with specificity towards breast, lung, and/or pancreatic cancer, we showed the feasibility of pVIII major coat proteins to significantly increase the throughput of targeting ligand screening in a common nanomedicine core. Phage protein-modified Lipodox samples showed an average doxorubicin recovery of 82.8% across all samples with 100% of protein incorporation in the correct orientation (N-terminus exposed. Following cytotoxicity screening in a doxorubicin-sensitive breast cancer line (MCF-7, three major groups of ligands were identified. Ligands showing the most improved cytotoxicity included: DMPGTVLP, ANGRPSMT, VNGRAEAP, and ANDVYLD showing a 25-fold improvement (p < 0.05 in toxicity. Similarly DGQYLGSQ, ETYNQPYL, and GSSEQLYL ligands with specificity towards a doxorubicin-insensitive pancreatic cancer line (PANC-1 showed significant increases in toxicity (2-fold; p < 0.05. Thus, we demonstrated proof-of-concept that pVIII major coat proteins can be screened in significantly higher throughput to identify novel ligands displaying improved therapeutic activity in a desired cancer phenotype.

  11. Fatty acid synthase plays a role in cancer metabolism beyond providing fatty acids for phospholipid synthesis or sustaining elevations in glycolytic activity.

    Science.gov (United States)

    Hopperton, Kathryn E; Duncan, Robin E; Bazinet, Richard P; Archer, Michael C

    2014-01-15

    Fatty acid synthase is over-expressed in many cancers and its activity is required for cancer cell survival, but the role of endogenously synthesized fatty acids in cancer is unknown. It has been suggested that endogenous fatty acid synthesis is either needed to support the growth of rapidly dividing cells, or to maintain elevated glycolysis (the Warburg effect) that is characteristic of cancer cells. Here, we investigate both hypotheses. First, we compared utilization of fatty acids synthesized endogenously from (14)C-labeled acetate to those supplied exogenously as (14)C-labeled palmitate in the culture medium in human breast cancer (MCF-7 and MDA-MB-231) and untransformed breast epithelial cells (MCF-10A). We found that cancer cells do not produce fatty acids that are different from those derived from exogenous palmitate, that these fatty acids are esterified to the same lipid and phospholipid classes in the same proportions, and that their distribution within neutral lipids is not different from untransformed cells. These results suggest that endogenously synthesized fatty acids do not fulfill a specific function in cancer cells. Furthermore, we observed that cancer cells excrete endogenously synthesized fatty acids, suggesting that they are produced in excess of requirements. We next investigated whether lipogenic activity is involved in the maintenance of high glycolytic activity by culturing both cancer and non-transformed cells under anoxic conditions. Although anoxia increased glycolysis 2-3 fold, we observed no concomitant increase in lipogenesis. Our results indicate that breast cancer cells do not have a specific qualitative or quantitative requirement for endogenously synthesized fatty acids and that increased de novo lipogenesis is not required to sustain elevations in glycolytic activity induced by anoxia in these cells.

  12. EVALUATION OF LEAKAGE FROM FUME HOODS USING TRACER GAS, TRACER NANOPARTICLES AND NANOPOWDER HANDLING TEST METHODOLOGIES

    OpenAIRE

    Dunn, Kevin H.; Tsai, Candace Su-Jung; Woskie, Susan R.; Bennett, James S.; Garcia, Alberto; Ellenbecker, Michael J.

    2014-01-01

    The most commonly reported control used to minimize workplace exposures to nanomaterials is the chemical fume hood. Studies have shown, however, that significant releases of nanoparticles can occur when materials are handled inside fume hoods. This study evaluated the performance of a new commercially available nano fume hood using three different test protocols. Tracer gas, tracer nanoparticle, and nanopowder handling protocols were used to evaluate the hood. A static test procedure using tr...

  13. An inexpensive field fluorometer for hydrogeological tracer tests with three tracers and turbidity measurement

    OpenAIRE

    Schnegg, Pierre-André

    2005-01-01

    The Geomagnetism Group of the University of Neuchâtel has recently designed a flow-through field fluorometer with added spectral capabilities for hydrological tracer tests. This instrument is equipped with four optical axes allowing water sample illumination with four independent light sources at different wavelenghs covering the full spectrum from UV to red. As many as three conveniently selected (dye) tracers can be simultaneously measured and separeted from a cocktail. Careful turbidity me...

  14. Specific genes involved in synthesis and editing of heparan sulfate proteoglycans show altered expression patterns in breast cancer

    Directory of Open Access Journals (Sweden)

    Fernández-Vega Iván

    2013-01-01

    Full Text Available Abstract Background The expression of a specific set of genes controls the different structures of heparan sulfate proteoglycans (HSPGs, which are involved in the growth, invasion and metastatic properties of cancerous cells. The purpose of this study is to increase knowledge of HSPG alterations in breast cancer. Methods Twenty-three infiltrating ductal adenocarcinomas (IDCs, both metastatic and non-metastatic were studied. A transcriptomic approach to the structure of heparan sulfate (HS chains was used, employing qPCR to analyze both the expression of the enzymes involved in their biosynthesis and editing, as well as the proteoglycan core proteins. Since some of these proteoglycans can also carry chondroitin sulfate chains, we extended the study to include the genes involved in the biosynthesis of these glycosaminoglycans. Histochemical techniques were also used to analyze tissular expression of particular genes showing significant expression differences, of potential interest. Results No significant change in transcription was detected in approximately 70% of analyzed genes. However, 13 demonstrated changes in both tumor types (40% showing more intense deregulation in the metastatic, while 5 genes showed changes only in non-metastatic tumors. Changes were related to 3 core proteins: overexpression of syndecan-1 and underexpression of glypican-3 and perlecan. HS synthesis was affected by lower levels of some 3-O-sulfotransferase transcripts, the expression of NDST4 and, only in non metastatic tumors, higher levels of extracellular sulfatases. Furthermore, the expression of chondroitin sulfate also was considerably affected, involving both the synthesis of the saccharidic chains and sulfations at all locations. However, the pro-metastatic enzyme heparanase did not exhibit significant changes in mRNA expression, although in metastatic tumors it appeared related to increased levels of the most stable form of mRNA. Finally, the expression of

  15. PET tracers for somatostatin receptor imaging of neuroendocrine tumors

    DEFF Research Database (Denmark)

    Johnbeck, Camilla Bardram; Knigge, Ulrich; Kjær, Andreas

    2014-01-01

    Neuroendocrine tumors have shown rising incidence mainly due to higher clinical awareness and better diagnostic tools over the last 30 years. Functional imaging of neuroendocrine tumors with PET tracers is an evolving field that is continuously refining the affinity of new tracers in the search...... these PET tracers further....

  16. Egg white-mediated green synthesis of silver nanoparticles with excellent biocompatibility and enhanced radiation effects on cancer cells

    Directory of Open Access Journals (Sweden)

    Lu RQ

    2012-04-01

    Full Text Available Renquan Lu1, Dapeng Yang2, Daxiang Cui2, Zhongyang Wang3, Lin Guo11Department of Clinical Laboratory, Fudan University Shanghai Cancer Center, Shanghai, 2Department of Bio-Nano-Science and Engineering, National Key Laboratory of Nano/Micro Fabrication Technology, Key Laboratory for Thin Film and Microfabrication of Ministry of Education, Institute of Micro-Nano Science and Technology, Shanghai Jiao Tong University, Shanghai, 3College of Chemistry and Chemical Engineering, Yantai University, Shan Dong Province, People's Republic of ChinaAbstract: A simple, cost-effective, and environmentally friendly approach to the aqueous-phase synthesis of silver (Ag nanoparticles was demonstrated using silver nitrate (AgNO3 and freshly extracted egg white. The bio-conjugates were characterized by UV-visible spectroscopy, transmission electron microscopy, Fourier transform infrared spectrometry, and dynamic light scattering. These results indicated that biomolecule-coated Ag nanoparticles are predominantly spherical in shape with an average size of 20 nm. The proteins of egg white, which have different functional groups, played important roles in reducing Ag+ and maintaining product attributes such as stability and dispersity. In vitro cytotoxicity assays showed that these Ag-protein bio-conjugates showed good biocompatibility with mouse fibroblast cell lines 3T3. Furthermore, X-ray irradiation tests on 231 tumor cells suggested that the biocompatible Ag-protein bio-conjugates enhanced the efficacy of irradiation, and thus may be promising candidates for use during cancer radiation therapy.Keywords: green chemistry, biosynthesis, egg white, Ag nanoparticles, X-ray irradiation

  17. Benzofuran as a promising scaffold for the synthesis of antimicrobial and antibreast cancer agents: A review

    Directory of Open Access Journals (Sweden)

    Ghadamali Khodarahmi

    2015-01-01

    Full Text Available Benzofuran as an important heterocyclic compound is extensively found in natural products as well as synthetic materials. Since benzofuran drivatives display a diverse array of pharmacological activities, an interest in developing new biologically active agents from benzofuran is still under consideration. This review highlights recent findings on biological activities of benzofuran derivatives as antimicrobial and antibreast cancer agents and lays emphasis on the importance of benzofurans as a major source for drug design and development.

  18. Synthesis of a drug delivery vehicle for cancer treatment utilizing DNA-functionalized gold nanoparticles

    Science.gov (United States)

    Brann, Tyler

    The treatment of cancer with chemotherapeutic agents has made great strides in the last few decades but still introduces major systemic side effects. The potent drugs needed to kill cancer cells often cause irreparable damage to otherwise healthy organs leading to further morbidity and mortality. A therapy with intrinsic selective properties and/or an inducible activation has the potential to change the way cancer can be treated. Gold nanoparticles (GNPs) are biocompatible and chemically versatile tools that can be readily functionalized to serve as molecular vehicles. The ability of these particles to strongly absorb light with wavelengths in the therapeutic window combined with the heating effect of surface plasmon resonance makes them uniquely suited for noninvasive heating in biologic applications. Specially designed DNA aptamers have shown their ability to serve as drug carriers through intercalation as well as directly acting as therapeutic agents. By combining these separate molecules a multifaceted drug delivery vehicle can be created with great potential as a selective and controllable treatment for cancer. Oligonucleotide-coated GNPs have been created using spherical GNPs but little work has been reported using gold nanoplates in this way. Using the Diasynth method gold nanoplates were produced to absorb strongly in the therapeutic near infrared (nIR) window. These particles were functionalized with two DNA oligonucleotides: one serving as an intercalation site for doxorubicin, and another, AS1411, serving directly as an anticancer targeting/therapeutic agent. These functional particles were fully synthesized and processed along with confirmation of DNA functionalization and doxorubicin intercalation. Doxorubicin is released via denaturation of the DNA structure into which doxorubicin is intercalated upon the heating of the gold nanoplate well above the DNA melting temperature. This temperature increase, due to light stimulation of surface plasmon

  19. Prostate Cancer Evaluation: Design, Synthesis and Evaluation of Novel Enzyme-Activated Proton MRI Contrast Agents

    Science.gov (United States)

    2010-10-01

    Partin AW, Carter HB , Piantadosi S., Marshall FF, Nelson WG, 1999, Induction of immunity to prostate cancer antigens: Results of a clinical trial of...Takayasu S, Maeda M, Tsuji A, Chemilumiscent enzyme immunoassay using β-D-galactosidase as the label and the bis(2,4,6-trichlorophenyl)oxalate...derivatives as substrate and its applications to enzyme immunoassay and DNA probe assay, Anal. Biochem., 1991, 199, 238- 242. 56. Jain VK, Magrath IT, A

  20. 5-Alkynyl-2'-deoxyuridines: Chromatography-free synthesis and cytotoxicity evaluation against human breast cancer cells

    OpenAIRE

    Meneni, Srinivasarao; Ott, Ingo; Sergeant, Craig D.; Sniady, Adam; Gust, Ronald; Dembinski, Roman

    2007-01-01

    Starting with 5-iodo-2'-deoxyuridine, a series of 5-alkynyl-2'-deoxyuridines (with n-propyl, cyclopropyl, 1-hydroxycyclohexyl, p-tolyl, p-tert-butylphenyl, p-pentylphenyl, and trimethylsilyl alkyne substituents) have been synthesized via the palladium-catalyzed (Sonogashira) coupling reaction followed by a simplified isolation protocol (76–94% yield). The cytotoxic activity of modified nucleosides against MCF-7 and MDA-MB-231 human breast cancer cells has been determined in vitro. 5-Ethynyl-2...

  1. Synthesis and Cytotoxic Evaluation of a Series of 2-Amino-Naphthoquinones against Human Cancer Cells

    Directory of Open Access Journals (Sweden)

    Thiago A. P. de Moraes

    2014-08-01

    Full Text Available The cytotoxicity of a series of aminonaphthoquinones resulting from the reaction of suitable aminoacids with 1,4-naphthoquinone was assayed against SF-295 (glioblastoma, MDAMB-435 (breast, HCT-8 (colon, HCT-116 (colon, HL-60 (leukemia, OVCAR-8 (ovarian, NCI-H358M (bronchoalveolar lung carcinoma and PC3-M (prostate cancer cells and also against PBMC (peripheral blood mononuclear cells. The results demonstrated that all the synthetic aminonaphthoquinones had relevant cytotoxic activity against all human cancer lines used in this experiment. Five of the compounds showed high cytotoxicity and selectivity against all cancer cell lines tested (IC50 = 0.49 to 3.89 µg·mL−1. The title compounds were less toxic to PBMC, since IC50 was 1.5 to eighteen times higher (IC50 = 5.51 to 17.61 µg·mL−1 than values shown by tumour cell lines. The mechanism of cell growth inhibition and structure–activity relationships remains as a target for future investigations.

  2. Design, synthesis and cytotoxicity studies of dithiocarbamate ester derivatives of emetine in prostate cancer cell lines.

    Science.gov (United States)

    Akinboye, Emmanuel S; Bamji, Zebalda D; Kwabi-Addo, Bernard; Ejeh, David; Copeland, Robert L; Denmeade, Samuel R; Bakare, Oladapo

    2015-09-01

    A small library of emetine dithiocarbamate ester derivatives were synthesized in 25-86% yield via derivatization of the N2'- position of emetine. Anticancer evaluation of these compounds in androgen receptor positive LNCaP and androgen receptor negative PC3 and DU145 prostate cancer cell lines revealed time dependent and dose-dependent cytotoxicity. With the exception of compound 4c, all the dithiocarbamate ester analogs in this study showed appreciable potency in all the prostate cancer cell lines (regardless of whether it is androgen receptor positive or negative) with a cytotoxicity IC50 value ranging from 1.312 ± 0.032 μM to 5.201 ± 0.125 μM by day 7 of treatment. Compared to the sodium dithiocarbamate salt 1, all the dithiocarbamate ester analogs (2 and 4a-4 g) displayed lower cytotoxicity than compound 1 (PC3, IC50 = 0.087 ± 0.005 μM; DU145, IC50 = 0.079 ± 0.003 μM and LNCaP, IC50 = 0.079 ± 0.003 μM) on day 7 of treatment. Consequently, it appears that S-alkylation of compound 1 leads to a more stable dithiocarbamate ester derivative that resulted in lower anticancer activity in the prostate cancer cell lines.

  3. Synthesis, anti-breast cancer activity, and molecular modeling of some benzothiazole and benzoxazole derivatives.

    Science.gov (United States)

    Abdelgawad, Mohamed A; Belal, Amany; Omar, Hany A; Hegazy, Lamees; Rateb, Mostafa E

    2013-07-01

    A new series of benzothiazoles and benzoxazoles was synthesized using 4-benzothiazol-2-yl-phenylamine and 4-benzoxazol-2-yl-phenylamine as starting materials. All the prepared compounds were evaluated for their antitumor activities against human breast cancer cell lines, MCF-7 and MDA-231, using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability analysis. Almost all the tested compounds revealed potent antitumor activity, especially the N-methyl piperazinyl substituted derivatives 6f and 6c, which displayed the most potent inhibitory activity with IC50 values ranging from 8 to 17 nM. Docking the synthesized compounds into the epidermal growth factor receptor (EGFR), which is highly expressed in breast cancer, was employed to explore the possible interactions of these compounds with the EGFR. The activity of the reported compounds supports its clinical promise as a component of therapeutic strategies for cancer, for which high concentrations of chemotherapeutic agents are always a major limitation.

  4. Acupoints Stimulation for Anxiety and Depression in Cancer Patients: A Quantitative Synthesis of Randomized Controlled Trials.

    Science.gov (United States)

    Wang, Tao; Deng, Renli; Tan, Jing-Yu; Guan, Feng-Guang

    2016-01-01

    This study aims at concluding the current evidence on the therapeutic effects of acupoints stimulation for cancer patients with anxiety and depression. Randomized controlled trials using acupoints stimulation for relieving anxiety and/or depression in cancer patients were searched, and 11 studies were finally included, of which eight trials compared acupoints stimulation with standard methods of treatment/care, and acupoints stimulation showed significantly better effects in improving depression than using standard methods of treatment/care. Four studies compared true acupoints stimulation with sham methods, and no significant differences can be found between groups for either depression or anxiety, although the pooled effects still favored true intervention. For the five studies that evaluated sleep quality, the results were conflicting, with three supporting the superiority of acupoints stimulation in improving sleep quality and two demonstrating no differences across groups. Acupoints stimulation seems to be an effective approach in relieving depression and anxiety in cancer patients, and placebo effects may partially contribute to the benefits. However, the evidence is not conclusive due to the limited number of included studies and the clinical heterogeneity identified among trials. More rigorous designed randomized, sham-controlled studies are necessary in future research.

  5. Acupoints Stimulation for Anxiety and Depression in Cancer Patients: A Quantitative Synthesis of Randomized Controlled Trials

    Directory of Open Access Journals (Sweden)

    Tao Wang

    2016-01-01

    Full Text Available This study aims at concluding the current evidence on the therapeutic effects of acupoints stimulation for cancer patients with anxiety and depression. Randomized controlled trials using acupoints stimulation for relieving anxiety and/or depression in cancer patients were searched, and 11 studies were finally included, of which eight trials compared acupoints stimulation with standard methods of treatment/care, and acupoints stimulation showed significantly better effects in improving depression than using standard methods of treatment/care. Four studies compared true acupoints stimulation with sham methods, and no significant differences can be found between groups for either depression or anxiety, although the pooled effects still favored true intervention. For the five studies that evaluated sleep quality, the results were conflicting, with three supporting the superiority of acupoints stimulation in improving sleep quality and two demonstrating no differences across groups. Acupoints stimulation seems to be an effective approach in relieving depression and anxiety in cancer patients, and placebo effects may partially contribute to the benefits. However, the evidence is not conclusive due to the limited number of included studies and the clinical heterogeneity identified among trials. More rigorous designed randomized, sham-controlled studies are necessary in future research.

  6. Synthesis and apoptotic activity of new pyrazole derivatives in cancer cell lines.

    Science.gov (United States)

    Nitulescu, George Mihai; Draghici, Constantin; Olaru, Octavian Tudorel; Matei, Lilia; Ioana, Aldea; Dragu, Laura Denisa; Bleotu, Coralia

    2015-09-01

    We designed and synthesized new pyrazole thiourea chimeric derivatives and confirmed their structures by NMR and IR spectra. Apoptotic effects were studied in human cancer cells. The N-[(1-methyl-1H-pyrazol-4-yl)carbonyl]-N'-(3-bromophenyl)-thiourea compound (4b) exhibited the highest apoptosis-inducing effect. Compound 4b and the thiazole derivatives, 5b and 6b, increased the expression of tumor necrosis factor receptors TRAIL-R2 and TRAIL-R1, accompanied by down-modulation of pro-caspase 3 levels, and the augmentation of cleaved caspase 3. They also reduced the levels of apoptosis inhibitory proteins and the expression of the heat-shock proteins Hsp27 and Hsp70. All the tested pyrazole derivatives induced a concentration-dependent increase of cells in G2/M phases. The analysis of the experimental data indicates the reduction of Akt phosphorylation as the most probable cellular mechanism of action for the tested compounds. The in vitro study indicated that compound 4b could be a promising anti-cancer drug, to be further developed in animal models of cancer.

  7. Synthesis, characterization and in vitro study of biocompatible cinnamaldehyde functionalized magnetite nanoparticles (CPGF Nps for hyperthermia and drug delivery applications in breast cancer.

    Directory of Open Access Journals (Sweden)

    Kirtee D Wani

    Full Text Available Cinnamaldehyde, the bioactive component of the spice cinnamon, and its derivatives have been shown to possess anti-cancer activity against various cancer cell lines. However, its hydrophobic nature invites attention for efficient drug delivery systems that would enhance the bioavailability of cinnamaldehyde without affecting its bioactivity. Here, we report the synthesis of stable aqueous suspension of cinnamaldehyde tagged Fe3O4 nanoparticles capped with glycine and pluronic polymer (CPGF NPs for their potential application in drug delivery and hyperthermia in breast cancer. The monodispersed superparamagnetic NPs had an average particulate size of ∼ 20 nm. TGA data revealed the drug payload of ∼ 18%. Compared to the free cinnamaldehyde, CPGF NPs reduced the viability of breast cancer cell lines, MCF7 and MDAMB231, at lower doses of cinnamaldehyde suggesting its increased bioavailability and in turn its therapeutic efficacy in the cells. Interestingly, the NPs were non-toxic to the non-cancerous HEK293 and MCF10A cell lines compared to the free cinnamaldehyde. The novelty of CPGF nanoparticulate system was that it could induce cytotoxicity in both ER/PR positive/Her2 negative (MCF7 and ER/PR negative/Her2 negative (MDAMB231 breast cancer cells, the latter being insensitive to most of the chemotherapeutic drugs. The NPs decreased the growth of the breast cancer cells in a dose-dependent manner and altered their migration through reduction in MMP-2 expression. CPGF NPs also decreased the expression of VEGF, an important oncomarker of tumor angiogenesis. They induced apoptosis in breast cancer cells through loss of mitochondrial membrane potential and activation of caspase-3. Interestingly, upon exposure to the radiofrequency waves, the NPs heated up to 41.6 °C within 1 min, suggesting their promise as a magnetic hyperthermia agent. All these findings indicate that CPGF NPs prove to be potential nano-chemotherapeutic agents in breast cancer.

  8. Combinatorial Synthesis for the Expedited Discovery of Novel Selective Antiestrogens for Breast Cancer Prevention and Therapy

    Science.gov (United States)

    2001-09-01

    Combinatorial organic synthesis of highly functionalized pyrrolidines: Identification of a potent angiotensin converting enzyme inhibitor from a...hexane to afford white powder (83%): mnp 158- 159°C, ’H NMR (CDC13) N-(4-Hydroxyphenyl)-N-(1,1,1-trifluoro-2-phenethyl)-4- 6 5.91 (br s, 1H), 6.30...off-white powder (59%): mnp 191.5-193 °C; IH anal. (C21H16F 3NO2S.0.3 H2O): C, 61.70; H, 4.09; N, NMR (MeOD) 6 6.10 (br s, 2H), 6.59 (app q, 2H, 3.43

  9. Tracer Diffusion Mechanism in Amorphous Solids

    Directory of Open Access Journals (Sweden)

    P. K. Hung

    2011-01-01

    Full Text Available Tracer diffusion in amorphous solid is studied by mean of nB-bubble statistic. The nB-bubble is defined as a group of atoms around a spherical void and large bubble that represents a structural defect which could be eliminated under thermal annealing. It was found that amorphous alloys such as CoxB100−x (x=90, 81.5 and 70 and Fe80P20 suffer from a large number of vacancy bubbles which function like diffusion vehicle. The concentration of vacancy bubble weakly depends on temperature, but essentially on the relaxation degree of considered sample. The diffusion coefficient estimated for proposed mechanism via vacancy bubbles is in a reasonable agreement with experiment for actual amorphous alloys. The relaxation effect for tracer diffusion in amorphous alloys is interpreted by the elimination of vacancy bubbles under thermal annealing.

  10. Molecules as tracers of galaxy evolution

    DEFF Research Database (Denmark)

    Costagliola, F.; Aalto, S.; I. Rodriguez, M.;

    2011-01-01

    We investigate the molecular gas properties of a sample of 23 galaxies in order to find and test chemical signatures of galaxy evolution and to compare them to IR evolutionary tracers. Observation at 3 mm wavelengths were obtained with the EMIR broadband receiver, mounted on the IRAM 30 m telesco...... detect the molecule in its vibrationally excited state.We find low HNC/HCN line ratios (...

  11. The medical applications of radioactive tracers

    Energy Technology Data Exchange (ETDEWEB)

    Hamilton, J.G.

    1947-12-31

    This report provides a broad yet in depth overview of the use of radioactive materials as tracers in medicine and biology for the period of 1935--1947. Particular attention is paid to is of radio-sodium, radio-iodine, radio-iron, radio-phosphorus, radio-strontium, and fission products. The main thrust of this paper is human rather than animal work and focuses in work that has been published.

  12. Glycogen synthesis correlates with androgen-dependent growth arrest in prostate cancer

    Directory of Open Access Journals (Sweden)

    Gorin Frederic A

    2005-03-01

    Full Text Available Abstract Background Androgen withdrawal in normal prostate or androgen-dependent prostate cancer is associated with the downregulation of several glycolytic enzymes and with reduced glucose uptake. Although glycogen metabolism is known to regulate the intracellular glucose level its involvement in androgen response has not been studied. Methods We investigated the effects of androgen on glycogen phosphorylase (GP, glycogen synthase (GS and on glycogen accumulation in the androgen-receptor (AR reconstituted PC3 cell line containing either an empty vector (PC3-AR-V or vector with HPV-E7 (PC3-AR-E7 and the LNCaP cell line. Results Androgen addition in PC3 cells expressing the AR mimics androgen ablation in androgen-dependent prostate cells. Incubation of PC3-AR-V or PC3-AR-E7 cells with the androgen R1881 induced G1 cell cycle arrest within 24 hours and resulted in a gradual cell number reduction over 5 days thereafter, which was accompanied by a 2 to 5 fold increase in glycogen content. 24 hours after androgen-treatment the level of Glucose-6-P (G-6-P had increased threefold and after 48 hours the GS and GP activities increased twofold. Under this condition inhibition of glycogenolysis with the selective GP inhibitor CP-91149 enhanced the increase in glycogen content and further reduced the cell number. The androgen-dependent LNCaP cells that endogenously express AR responded to androgen withdrawal with growth arrest and increased glycogen content. CP-91149 further increased glycogen content and caused a reduction of cell number. Conclusion Increased glycogenesis is part of the androgen receptor-mediated cellular response and blockage of glycogenolysis by the GP inhibitor CP-91149 further increased glycogenesis. The combined use of a GP inhibitor with hormone therapy may increase the efficacy of hormone treatment by decreasing the survival of prostate cancer cells and thereby reducing the chance of cancer recurrence.

  13. Synthesis, structural characterization, and anticancer activity of a monobenzyltin compound against MCF-7 breast cancer cells

    Directory of Open Access Journals (Sweden)

    Fani S

    2015-11-01

    Full Text Available Somayeh Fani,1 Behnam Kamalidehghan,1 Kong Mun Lo,2 Najihah Mohd Hashim,1 Kit May Chow,2 Fatemeh Ahmadipour1 1Department of Pharmacy, Faculty of Medicine, 2Department of Chemistry, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia Abstract: A new monoorganotin Schiff base compound, [N-(3,5-dichloro-2-oxidobenzylidene-4-chlorobenzyhydrazidato](o-methylbenzylaquatin(IV chloride, (compound C1, was synthesized, and its structural features were investigated by spectroscopic techniques and single-crystal X-ray diffractometry. Compound C1 was exposed to several human cancer cell lines, including breast adenocarcinoma cell lines MCF-7 and MDA-MB-231, ovarian adenocarcinoma cell lines Skov3 and Caov3, and prostate cancer cell line PC3, in order to examine its cytotoxic effect for different forms of cancer. Human hepatic cell line WRL-68 was used as a normal cell line. We concentrated on the MCF-7 cell line to detect possible underlying mechanism involvement of compound C1. 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay revealed the strongest cytotoxicity of compound C1 against MCF-7 cells, with a half maximal inhibitory concentration (IC50 value of 2.5±0.50 µg/mL after 48 hours treatment. The IC50 value was >30 µg/mL in WRL-68 cells. Induced antiproliferative activity of compound C1 for MCF-7 cells was further confirmed by lactate dehydrogenase, reactive oxygen species, acridine orange/propidium iodide staining, and DNA fragmentation assays. A significant increase of lactate dehydrogenase release in treated cells was observed via fluorescence analysis. Luminescent analysis showed significant growth in intracellular reactive oxygen species production after treatment. Morphological changes of necrosis and early and late apoptosis stages were observed in treated cells after staining with acridine orange/propidium iodide. DNA fragmentation was observed as a characteristic of apoptosis in treated cells. Results of the

  14. Synthesis, characterization, and in vivo efficacy evaluation of PGG–docetaxel conjugate for potential cancer chemotherapy

    Directory of Open Access Journals (Sweden)

    Jiang X

    2012-02-01

    Full Text Available Danbo Yang1, Sang Van2, Yingyi Shu1, Xiaoqing Liu1, Yangfeng Ge1, Xinguo Jiang3, Yi Jin2, Lei Yu1,21Biomedical Engineering and Technology Institute, Institutes for Advanced Interdisciplinary Research, East China Normal University, Shanghai, People’s Republic of China; 2Biomedical Group, Nitto Denko Technical Corporation, CA, USA; 3School of Pharmacy, Fudan University, Shanghai, People’s Republic of ChinaAim: This work is intended to develop and evaluate a biopolymeric poly(L-γ-glutamyl-glutamine (PGG–docetaxel (DTX conjugate that can spontaneously self-assemble in aqueous solutions to become nanoparticles.Methods: DTX was covalently attached to hydrophilic PGG by direct esterification, and the conjugate was characterized by proton nuclear magnetic resonance spectroscopy, molecular weight gel permeation chromatography, solubility, size distribution and morphology, and hemolysis. Conjugated DTX was found to have 2000 times improved water solubility compared with free DTX. Dynamic light scattering, transmission electron microscopy, and atomic force microscopy revealed the particle size, distribution and morphology of the PGG–DTX conjugate. In addition, the conjugate was further tested for in vitro cytotoxicity and in vivo antitumor efficacy on the human non-small cell lung cancer cell line NCI-H460.Results: Conjugated DTX was found to have 2000 times improved water solubility compared with free DTX. The conjugate formed nanoparticles with an average diameter of 30 nm in spherical shape and unimodal particle size distribution. The conjugate exhibited about 2% hemolysis at 10 mg/mL, compared with 56% for Tween 80® at 0.4 mg/mL, and 33% for Cremophor EL® at 10 mg/mL. In addition, the conjugate was further tested for in vitro cytotoxicity and in vivo antitumor efficacy on the human non-small cell lung cancer cell line NCI-H460. As expected, conjugated DTX exhibited lower cytotoxicity compared to that of free DTX, in concentration

  15. Xenograft Studies of Fatty Acid Synthesis Inhibition as Novel Therapy for Breast Cancer

    Science.gov (United States)

    2000-08-01

    membrane to regulate fatty acid oxidation by inhibition of carnitine palmitoyltransferase 1 (CPT- 1). Inhibition of CPT-1 has been shown to sensitize...Fat Storage" Granted U.S.application filed November 28, 1996; formal issuance occurred in 1999. Inhibition of Carnitine Palmitoyltransferase-1 (CPT-1...carnsatuo- cancer cells in serum supplemented culture. Rather, high levels of theC oA and acetyl-C oA to produce predom inantly the 16-carbon satu- s b t a

  16. Tracer technology modeling the flow of fluids

    CERN Document Server

    Levenspiel, Octave

    2012-01-01

    A vessel’s behavior as a heat exchanger, absorber, reactor, or other process unit is dependent upon how fluid flows through the vessel.  In early engineering, the designer would assume either plug flow or mixed flow of the fluid through the vessel.  However, these assumptions were oftentimes inaccurate, sometimes being off by a volume factor of 100 or more.  The result of this unreliable figure produced ineffective products in multiple reaction systems.   Written by a pioneering researcher in the field of chemical engineering, the tracer method was introduced to provide more accurate flow data.  First, the tracer method measured the actual flow of fluid through a vessel.  Second, it developed a suitable model to represent the flow in question.  Such models are used to follow the flow of fluid in chemical reactors and other process units, like in rivers and streams, or solid and porous structures.  In medicine, the tracer method is used to study the flow of chemicals—harmful  and harmless—in the...

  17. Very Massive Tracers and Higher Derivative Biases

    CERN Document Server

    Fujita, Tomohiro; Senatore, Leonardo; Vlah, Zvonimir; Angulo, Raul

    2016-01-01

    Most of the upcoming cosmological information will come from analyzing the clustering of the Large Scale Structures (LSS) of the universe through LSS or CMB observations. It is therefore essential to be able to understand their behavior with exquisite precision. The Effective Field Theory of Large Scale Structures (EFTofLSS) provides a consistent framework to make predictions for LSS observables in the mildly non-linear regime. In this paper we focus on biased tracers. We argue that in calculations at a given order in the dark matter perturbations, highly biased tracers will underperform because of their larger higher derivative biases. A natural prediction of the EFTofLSS is therefore that by simply adding higher derivative biases, all tracers should perform comparably well. We implement this prediction for the halo-halo and the halo-matter power spectra at one loop, and the halo-halo-halo, halo-halo-matter, and halo-matter-matter bispectra at tree-level, and compare with simulations. We find good agreement ...

  18. Synthesis and Biological Evaluation of Lipophilic 1,4-Naphthoquinone Derivatives against Human Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Shao-Hung Wang

    2015-06-01

    Full Text Available To examine the effect of hydrophobicity on the anticancer activity of 1,4-naphthoquinone derivatives, a series of compounds bearing a 2-O-alkyl-, 3-C-alkyl- or 2/3-N-morpholinoalkyl group were synthesized and evaluated for their anticancer activity against five human cancer cell lines in vitro. The cytotoxicity of these derivatives was assayed against HT-29, SW480, HepG2, MCF-7 and HL-60 cells by the MTT assay. Among them, 2-hydroxy-3-farnesyl-1,4-naphthoquinone (11a was found to be the most cytotoxic against these cell lines. Our results showed that the effectiveness of compound 11a may be attributed to its suppression of the survival of HT-29. Secondly, in the Hoechst 33258 staining test, compound 11a-treated cells exhibited nuclear condensation typical of apoptosis. Additionally, cell cycle analysis by flow cytometry indicated that compound 11a arrested HT-29 cells in the S phase. Furthermore, cell death detected by Annexin V-FITC/propidium iodide staining showed that compound 11a efficiently induced apoptosis of HT-29 in a concentration-dependent manner. Taken together, compound 11a effectively inhibits colon cancer cell proliferation and may be a potent anticancer agent.

  19. Green synthesis of pullulan stabilized gold nanoparticles for cancer targeted drug delivery.

    Science.gov (United States)

    Ganeshkumar, Moorthy; Ponrasu, Thangavel; Raja, Modhugoor Devendiran; Subamekala, Muthaiya Kannappan; Suguna, Lonchin

    2014-09-15

    The aim of this study was to synthesize green chemistry based gold nanoparticles using liver specific biopolymer and to develop a liver cancer targeted drug delivery system with enhanced efficacy and minimal side effects. Pullulan stabilized gold nanoparticles (PAuNPs) were coupled with 5-Fluorouracil (5-Fu) and folic acid (Fa) which could be used as a tool for targeted drug delivery and imaging of cancer. The toxicity of 5-Fu, 5-Fu adsorbed gold nanoparticles (5-Fu@AuNPs), Fa-coupled 5-Fu adsorbed gold nanoparticles (5-Fu@AuNPs-Fa), was studied using zebrafish embryo as an in vivo model. The in vitro cytotoxicity of free 5-Fu, 5-Fu@AuNPs, 5-Fu@AuNPs-Fa against HepG2 cells was studied and found that the amount of 5-Fu required to achieve 50% of growth of inhibition (Ic50) was much lower in 5-Fu@AuNP-Fa than in free 5-Fu, 5-Fu@AuNPs. The in vivo biodistribution of PAuNPs showed that higher amount of gold had been accumulated in liver (54.42±5.96 μg) than in other organs.

  20. Synthesis of folate- pegylated polyester nanoparticles encapsulating ixabepilone for targeting folate receptor overexpressing breast cancer cells.

    Science.gov (United States)

    Siafaka, P; Betsiou, M; Tsolou, A; Angelou, E; Agianian, B; Koffa, M; Chaitidou, S; Karavas, E; Avgoustakis, K; Bikiaris, D

    2015-12-01

    The aim of this study was the preparation of novel polyester nanoparticles based on folic acid (FA)-functionalized poly(ethylene glycol)-poly(propylene succinate) (PEG-PPSu) copolymer and loaded with the new anticancer drug ixabepilone (IXA). These nanoparticles may serve as a more selective (targeted) treatment of breast cancer tumors overexpressing the folate receptor. The synthesized materials were characterized by (1)H-NMR, FTIR, XRD and DSC. The nanoparticles were prepared by a double emulsification and solvent evaporation method and characterized with regard to their morphology by scanning electron microscopy, drug loading with HPLC-UV and size by dynamic light scattering. An average size of 195 nm and satisfactory drug loading efficiency (3.5%) were observed. XRD data indicated that IXA was incorporated into nanoparticles in amorphous form. The nanoparticles exhibited sustained drug release properties in vitro. Based on in vitro cytotoxicity studies, the blank FA-PEG-PPSu nanoparticles were found to be non-toxic to the cells. Fluorescent nanoparticles were prepared by conjugating Rhodanine B to PEG-PPSu, and live cell, fluorescence, confocal microscopy was applied in order to demonstrate the ability of FA-PEG-PPSu nanoparticles to enter into human breast cancer cells expressing the folate receptor.

  1. Synthesis, Characterization and Anti-Cancer Activity of Hydrazide Derivatives Incorporating a Quinoline Moiety

    Directory of Open Access Journals (Sweden)

    Murat Bingul

    2016-07-01

    Full Text Available Identification of the novel (E-N′-((2-chloro-7-methoxyquinolin-3-ylmethylene-3-(phenylthiopropanehydrazide scaffold 18 has led to the development of a new series of biologically active hydrazide compounds. The parent compound 18 and new quinoline derivatives 19–26 were prepared from the corresponding quinoline hydrazones and substituted carboxylic acids using EDC-mediated peptide coupling reactions. Further modification of the parent compound 18 was achieved by replacement of the quinoline moiety with other aromatic systems. All the newly synthesized compounds were evaluated for their anti-cancer activity against the SH-SY5Y and Kelly neuroblastoma cell lines, as well as the MDA-MB-231 and MCF-7 breast adenocarcinoma cell lines. Analogues 19 and 22 significantly reduced the cell viability of neuroblastoma cancer cells with micromolar potency and significant selectivity over normal cells. The quinoline hydrazide 22 also induced G1 cell cycle arrest, as well as upregulation of the p27kip1 cell cycle regulating protein.

  2. Effects of cadmium on estrogen receptor mediated signaling and estrogen induced DNA synthesis in T47D human breast cancer cells.

    Science.gov (United States)

    Zang, Yu; Odwin-Dacosta, Shelly; Yager, James D

    2009-01-30

    Cadmium (Cd) has been shown to bind to the human estrogen receptor (ER), yet studies on Cd's estrogenic effects have yielded inconsistent results. In this study, we investigated the effects of Cd on DNA synthesis and its simultaneous effects on both genomic (mediated by nuclear ER (nER)) and non-genomic (mediated by membrane-bound ER (mER)) signaling in human breast cancer derived T47D cells. No effects on DNA synthesis were observed for non-cytotoxic concentrations of CdCl(2) (0.1-1000 nM), and Cd did not increase progesterone receptor (PgR) or pS2 mRNA levels. However, Cd stimulated phosphorylation of ERK1/2 MAPK, detectable following 10 min and 18 h of treatment. The sustained Cd-induced ERK1/2 phosphorylation was inhibited by the ER antagonist ICI 182,780, suggesting the involvement of ER. In addition, Cd enhanced DNA synthesis and pS2 mRNA levels in estrogen (10 pM estradiol) treated T47D cells. The MEK1/2 specific inhibitor U0126 blocked DNA synthesis stimulated by estradiol (E2) and the E2-Cd mixtures. These findings indicate that the ERK1/2 signaling is critical in E2-related DNA synthesis. The sustained ERK1/2 phosphorylation may contribute to the Cd-induced enhancement of DNA synthesis and pS2 mRNA in mixture with low-concentration E2.

  3. Cancer

    Science.gov (United States)

    Cancer begins in your cells, which are the building blocks of your body. Normally, your body forms ... be benign or malignant. Benign tumors aren't cancer while malignant ones are. Cells from malignant tumors ...

  4. Potential impact of [{sup 18}F]3'-deoxy-3'-fluorothymidine versus [{sup 18}F]fluoro-2-deoxy-d-glucose in positron emission tomography for colorectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Francis, D.L. [Institute of Nuclear Medicine, Royal Free and University College Medical School, Middlesex Hospital, Mortimer Street, W1T 3AA, London (United Kingdom); Department of Surgery, Royal Free and University College Medical School, Middlesex Hospital, London (United Kingdom); Visvikis, D.; Costa, D.C.; Townsend, C.; Ell, P.J. [Institute of Nuclear Medicine, Royal Free and University College Medical School, Middlesex Hospital, Mortimer Street, W1T 3AA, London (United Kingdom); Arulampalam, T.H.A.; Taylor, I. [Department of Surgery, Royal Free and University College Medical School, Middlesex Hospital, London (United Kingdom); Luthra, S.K. [IRSL Cyclotron Unit, Hammersmith Hospital, London (United Kingdom)

    2003-07-01

    Fluorine-18 labelled fluoro-2-deoxy-d-glucose ({sup 18}FDG) positron emission tomography (PET) imaging demonstrates the increased glucose consumption of malignant cells, but problems with specificity have led to the development of new PET tracers. [{sup 18}F]3'-deoxy-3'-fluorothymidine ({sup 18}FLT) is a new tracer which images cellular proliferation by entering the salvage pathway of DNA synthesis. In this study we compared the cellular uptake of {sup 18}FLT and {sup 18}FDG in patients with colorectal cancer (CRC). Seventeen patients with 50 primary or metastatic CRC lesions were prospectively recruited. Lesions were initially identified using computed tomography. Patients underwent both {sup 18}FDG and {sup 18}FLT scanning. Semi-quantitative analysis of tracer uptake was carried out using standardised uptake values. All the primary tumours (n=6) were visualised by both tracers, with {sup 18}FDG showing on average twice the uptake of {sup 18}FLT. Similar uptake of both tracers was seen in lung and peritoneal lesions, with {sup 18}FLT imaging five of the six lung lesions and all of the peritoneal lesions. Of the 32 colorectal liver metastases, 11 (34%) were seen as avid for {sup 18}FLT, compared with 31 (97%) for {sup 18}FDG. No correlation was seen between the uptake of the two tracers (R{sup 2}=0.03). {sup 18}FLT shows a high sensitivity in the detection of extrahepatic disease but poor sensitivity for the imaging of colorectal liver metastases, making it unlikely to have a role as a diagnostic tracer in CRC. We have demonstrated that {sup 18}FDG and {sup 18}FLT image two distinct processes. The prognostic implications of the uptake of {sup 18}FLT need to be assessed in terms of response to chemoradiotherapy and survival. (orig.)

  5. Synthesis, characterization and cytotoxic evaluation of chitosan nanoparticles: in vitro liver cancer model

    Science.gov (United States)

    Loutfy, Samah A.; Alam El-Din, Hanaa M.; Elberry, Mostafa H.; Allam, Nanis G.; Hasanin, M. T. M.; Abdellah, Ahmed M.

    2016-09-01

    To evaluate the cytotoxic effect of chitosan nanoparticles (CS-NPs) on an in vitro human liver cancer cell model (HepG2) and their possible application as a drug delivery system, we synthesized water-soluble CS-NPs, investigated their properties and extensively evaluated their cytotoxic activity on the cellular and molecular levels. A human liver cancer cell line was used as a model of human liver cancer. The CS-NPs were characterized using transmission electron microscopy, Fourier transform infrared spectroscopy, and zeta analysis. The cytotoxic effects of the CS-NPs on HepG2 cells were monitored by sulforhodamine B colorimetric assays for cytotoxicity screening and flow cytometric analysis. Molecular investigations including DNA fragmentation and the expression of some apoptotic genes on the transcriptional RNA level were conducted. Treatment of HepG2 with different concentrations of 150 nm diameter CS-NPs did not show alteration of cell morphology after 24 h of cell exposure. Also, when cells were treated with 100 μg ml-1 of CS-NPs, 12% of them were killed and IC50 reached 239 μg ml-1 after 48 h of cell exposure. Flow cytometry evaluation of the CS-NPs revealed mild accumulation in the G2/M phase followed by cellular DNA fragmentation after 48 h of cell exposure. Extensive evaluation of the cytotoxic effect of the CS-NPs showed messenger RNA (mRNA) apoptotic gene expression (p53, Bak, Caspase3) after 24 h of cell exposure with no expression of the mRNA of the caspase 3 gene after 48 h of cell exposure, suggesting the involvement of an intrinsic apoptotic caspase-independent pathway by increasing the exposure time of 100 μg ml-1 of the CS-NPs. The engineered CS-NPs were controlled to a 150 nm size and charges of 40 mV and a concentration of 100 μg ml-1 revealed a genotoxic effect on HepG2 after 48 h of cell exposure through intrinsic apoptotic caspase-independent mechanisms. Further quantitative analysis on the molecular and protein levels is still required

  6. Additive controlled synthesis of gold nanorods (GNRs) for two-photon luminescence imaging of cancer cells.

    Science.gov (United States)

    Zhu, Jing; Yong, Ken-Tye; Roy, Indrajit; Hu, Rui; Ding, Hong; Zhao, Lingling; Swihart, Mark T; He, Guang S; Cui, Yiping; Prasad, Paras N

    2010-07-16

    Gold nanorods (GNRs) with a longitudinal surface plasmon resonance peak that is tunable from 600 to 1100 nm have been fabricated in a cetyl trimethylammoniumbromide (CTAB) micellar medium using hydrochloric acid and silver nitrate as additives to control their shape and size. By manipulating the concentrations of silver nitrate and hydrochloric acid, the aspect ratio of the GNRs was reliably and reproducibly tuned from 2.5 to 8. The GNRs were first coated with polyelectrolyte multilayers and then bioconjugated to transferrin (Tf) to target pancreatic cancer cells. Two-photon imaging excited from the bioconjugated GNRs demonstrated receptor-mediated uptake of the bioconjugates into Panc-1 cells, overexpressing the transferrin receptor (TfR). The bioconjugated GNR formulation exhibited very low toxicity, suggesting that it is biocompatible and potentially suitable for targeted two-photon bioimaging.

  7. Synthesis and Cytotoxic Activity on Human Cancer Cells of Novel Isoquinolinequinone-Amino Acid Derivatives.

    Science.gov (United States)

    Valderrama, Jaime A; Delgado, Virginia; Sepúlveda, Sandra; Benites, Julio; Theoduloz, Cristina; Buc Calderon, Pedro; Muccioli, Giulio G

    2016-09-08

    A variety of aminoisoquinoline-5,8-quinones bearing α-amino acids moieties were synthesized from 3-methyl-4-methoxycarbonylisoquinoline-5,8-quinone and diverse l- and d-α-amino acid methyl esters. The members of the series were evaluated for their cytotoxic activity against normal and cancer cell lines by using the (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) assay. From the current investigation, structure-activity relationships demonstrate that the location and structure of the amino acid fragment plays a significant role in the cytotoxic effects. Moderate to high cytotoxic activity was observed and four members, derived from l-alanine, l-leucine, l-phenylalanine, and d-phenylalanine, were selected as promising compounds by their IC50 ranging from 0.5 to 6.25 μM and also by their good selectivity indexes (≥2.24).

  8. 5-Alkynyl-2'-deoxyuridines: Chromatography-free synthesis and cytotoxicity evaluation against human breast cancer cells

    Science.gov (United States)

    Meneni, Srinivasarao; Ott, Ingo; Sergeant, Craig D.; Sniady, Adam; Gust, Ronald; Dembinski, Roman

    2007-01-01

    Starting with 5-iodo-2'-deoxyuridine, a series of 5-alkynyl-2'-deoxyuridines (with n-propyl, cyclopropyl, 1-hydroxycyclohexyl, p-tolyl, p-tert-butylphenyl, p-pentylphenyl, and trimethylsilyl alkyne substituents) have been synthesized via the palladium-catalyzed (Sonogashira) coupling reaction followed by a simplified isolation protocol (76–94% yield). The cytotoxic activity of modified nucleosides against MCF-7 and MDA-MB-231 human breast cancer cells has been determined in vitro. 5-Ethynyl-2'-deoxyuridine, the only nucleoside in the series containing a terminal acetylene, is the most potent inhibitor with IC50 (μM) 0.4 ± 0.3 for MCF-7 and 4.4 ± 0.4 for MDA-MB-231. PMID:17336074

  9. Synthesis and biological evaluation of nitric oxide-donating analogues of sulindac for prostate cancer treatment.

    Science.gov (United States)

    Nortcliffe, Andrew; Ekstrom, Alexander G; Black, James R; Ross, James A; Habib, Fouad K; Botting, Nigel P; O'Hagan, David

    2014-01-15

    A series of analogues of the non-steroidal anti-inflammatory drug (NSAID) sulindac 1 were synthesised tethered to nitric oxide (NO) donating functional groups. Sulindac shows antiproliterative effects against immortal PC3 cell lines. It was previously demonstrated that the effect can be enhanced when tethered to NO releasing groups such as nitrate esters, furoxans and sydnonimines. To explore this approach further, a total of fifty-six sulindac-NO analogues were prepared and they were evaluated as NO-releasing cytotoxic agents against prostate cancer (PCa) cell lines. Compounds 1k and 1n exhibited significant cytotoxic with IC50 values of 6.1±4.1 and 12.1±3.2μM, respectively, coupled with observed nitric oxide release.

  10. Synthesis of novel carbazole chalcones as radical scavenger, antimicrobial and cancer chemopreventive agents.

    Science.gov (United States)

    Bandgar, Babasaheb P; Adsul, Laxman K; Lonikar, Shrikant V; Chavan, Hemant V; Shringare, Sadanand N; Patil, Sachin A; Jalde, Shivkumar S; Koti, Basawaraj A; Dhole, Nagesh A; Gacche, Rajesh N; Shirfule, Amol

    2013-06-01

    A series of novel carbazole chalcones has been synthesised and evaluated for radical scavenging activity, cytotoxicity and antimicrobial activities. Compounds 12m, 12o and 12c exhibited good 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, compounds 12e, 12m and 12d were excellent hydroxyl radical scavengers and compounds 12a, 12e, 12g, 12n and 12m have shown inhibition of oxidative DNA damage induced by 2,2'-azobis (2-amidinopropane hydrochloride). Compounds 12j, 12i, 12n, 12c, 12m and 12e were most active against the selected cancer cell lines. Compounds 12a, 12e and 12m showed good antibacterial activity and compounds 12h and 12m have shown good antifungal activity. All the compounds were subjected for absorption, distribution, metabolism and excretion (ADME) predictions by computational method and found that these molecules could be considered as potential candidates for oral drug development.

  11. An in-vitro studies on green synthesis of gold nanoparticles against pathogens and cancer cells

    Directory of Open Access Journals (Sweden)

    V. Ramesh

    2015-11-01

    Full Text Available Nanotechnology is a most promising field for generating new applications in medicine. It is imperative to integrate nanoscience and medicine. The present investigation is highly warranted to through more light upon the gold nanoparticles reduced from gold salt through the active principle of medicinal plant. The special emphasis of investigation is the active principle along with gold nanoparticles against for cancer cells. The 70 - 90 nm sized particles were synthesized by using Diospyros ferrea and this confirmed by SEM. These gold nanoparticles showed a characteristic absorption peak at 540 nm in UV spectra. The possibility of protein as a stabilizing material in gold nanoparticles is revealed by FTIR analysis. Remarkably, as a result of wide screening on the application of newly synthesized gold nanoparticles their anticancer potential has been discovered using MTT assay. The antimicrobial activity of AuNPs showed effective against bacteria than the fungal strains.

  12. Additive controlled synthesis of gold nanorods (GNRs) for two-photon luminescence imaging of cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhu Jing; Roy, Indrajit; Hu Rui; Ding Hong; Zhao Lingling; He, Guang S; Prasad, Paras N [Institute for Lasers, Photonics and Biophotonics, University at Buffalo, State University of New York, Buffalo, NY 14260-4200 (United States); Yong, Ken-Tye [School of Electrical and Electronic Engineering, Nanyang Technological University, Singapore 639798 (Singapore); Swihart, Mark T [Department of Chemical and Biological Engineering, University at Buffalo, State University of New York, Buffalo, NY 14260-4200 (United States); Cui Yiping, E-mail: ktyong@ntu.edu.sg, E-mail: cyp@seu.edu.cn, E-mail: pnprasad@buffalo.edu [Advanced Photonics Center, School of Electronic Science and Engineering, Southeast University, Nanjing 210096 (China)

    2010-07-16

    Gold nanorods (GNRs) with a longitudinal surface plasmon resonance peak that is tunable from 600 to 1100 nm have been fabricated in a cetyl trimethylammoniumbromide (CTAB) micellar medium using hydrochloric acid and silver nitrate as additives to control their shape and size. By manipulating the concentrations of silver nitrate and hydrochloric acid, the aspect ratio of the GNRs was reliably and reproducibly tuned from 2.5 to 8. The GNRs were first coated with polyelectrolyte multilayers and then bioconjugated to transferrin (Tf) to target pancreatic cancer cells. Two-photon imaging excited from the bioconjugated GNRs demonstrated receptor-mediated uptake of the bioconjugates into Panc-1 cells, overexpressing the transferrin receptor (TfR). The bioconjugated GNR formulation exhibited very low toxicity, suggesting that it is biocompatible and potentially suitable for targeted two-photon bioimaging.

  13. Current radiosynthesis strategies for 5-HT2A receptor PET tracers

    DEFF Research Database (Denmark)

    Herth, Matthias M; Knudsen, Gitte M

    2015-01-01

    Serotonin 2A receptors have been implicated in various psychophysiological functions and disorders such as depression, Alzheimer's disease, or schizophrenia. Therefore, neuroimaging of this specific receptor is of significant clinical interest, and it is not surprising that many attempts have been...... made to develop a suitable 5-HT2A R positron emission tomography-tracer. In this review, we give an overview on the precursor, reference compound synthesis, and the preparation of promising 5-HT2A R radiopharmaceuticals applied in positron emission tomography. We also highlight possible learning...

  14. Intratumoral de novo steroid synthesis activates androgen receptor in castration-resistant prostate cancer and is upregulated by treatment with CYP17A1 inhibitors.

    Science.gov (United States)

    Cai, Changmeng; Chen, Sen; Ng, Patrick; Bubley, Glenn J; Nelson, Peter S; Mostaghel, Elahe A; Marck, Brett; Matsumoto, Alvin M; Simon, Nicholas I; Wang, Hongyun; Chen, Shaoyong; Balk, Steven P

    2011-10-15

    Relapse of castration-resistant prostate cancer (CRPC) that occurs after androgen deprivation therapy of primary prostate cancer can be mediated by reactivation of the androgen receptor (AR). One important mechanism mediating this AR reactivation is intratumoral conversion of the weak adrenal androgens DHEA and androstenedione into the AR ligands testosterone and dihydrotestosterone. DHEA and androstenedione are synthesized by the adrenals through the sequential actions of the cytochrome P450 enzymes CYP11A1 and CYP17A1, so that CYP17A1 inhibitors such as abiraterone are effective therapies for CRPC. However, the significance of intratumoral CYP17A1 and de novo androgen synthesis from cholesterol in CRPC, and the mechanisms contributing to CYP17A1 inhibitor resistance/relapse, remain to be determined. We report that AR activity in castration-resistant VCaP tumor xenografts can be restored through CYP17A1-dependent de novo androgen synthesis, and that abiraterone treatment of these xenografts imposes selective pressure for increased intratumoral expression of CYP17A1, thereby generating a mechanism for development of resistance to CYP17A1 inhibitors. Supporting the clinical relevance of this mechanism, we found that intratumoral expression of CYP17A1 was markedly increased in tumor biopsies from CRPC patients after CYP17A1 inhibitor therapy. We further show that CRPC cells expressing a progesterone responsive T877A mutant AR are not CYP17A1 dependent, but that AR activity in these cells is still steroid dependent and mediated by upstream CYP11A1-dependent intraturmoral pregnenolone/progesterone synthesis. Together, our results indicate that CRPCs resistant to CYP17A1 inhibition may remain steroid dependent and therefore responsive to therapies that can further suppress de novo intratumoral steroid synthesis.

  15. Regulation of DNA synthesis and the cell cycle in human prostate cancer cells and lymphocytes by ovine uterine serpin

    Directory of Open Access Journals (Sweden)

    Hansen Peter J

    2008-01-01

    Full Text Available Abstract Background Uterine serpins are members of the serine proteinase inhibitor superfamily. Like some other serpins, these proteins do not appear to be functional proteinase inhibitors. The most studied member of the group, ovine uterine serpin (OvUS, inhibits proliferation of several cell types including activated lymphocytes, bovine preimplantation embryos, and cell lines for lymphoma, canine primary osteosarcoma and human prostate cancer (PC-3 cells. The goal for the present study was to evaluate the mechanism by which OvUS inhibits cell proliferation. In particular, it was tested whether inhibition of DNA synthesis in PC-3 cells involves cytotoxic actions of OvUS or the induction of apoptosis. The effect of OvUS in the production of the autocrine and angiogenic cytokine interleukin (IL-8 by PC-3 cells was also determined. Finally, it was tested whether OvUS blocks specific steps in the cell cycle using both PC-3 cells and lymphocytes. Results Recombinant OvUS blocked proliferation of PC-3 cells at concentrations as low as 8 μg/ml as determined by measurements of [3H]thymidine incorporation or ATP content per well. Treatment of PC-3 cells with OvUS did not cause cytotoxicity or apoptosis or alter interleukin-8 secretion into medium. Results from flow cytometry experiments showed that OvUS blocked the entry of PC-3 cells into S phase and the exit from G2/M phase. In addition, OvUS blocked entry of lymphocytes into S phase following activation of proliferation with phytohemagglutinin. Conclusion Results indicate that OvUS acts to block cell proliferation through disruption of the cell cycle dynamics rather than induction of cytotoxicity or apoptosis. The finding that OvUS can regulate cell proliferation makes this one of only a few serpins that function to inhibit cell growth.

  16. CityFlux perfluorocarbon tracer experiments

    Science.gov (United States)

    Petersson, F. K.; Martin, D.; White, I. R.; Henshaw, S. J.; Nickless, G.; Longley, I.; Percival, C. J.; Gallagher, M.; Shallcross, D. E.

    2010-07-01

    In June 2006, two perfluorocarbon tracer experiments were conducted in central Manchester UK as part of the CityFlux campaign. The main aim was to investigate vertical dispersion in an urban area during convective conditions, but dispersion mechanisms within the street network were also studied. Paired receptors were used in most cases where one receptor was located at ground level and one at roof level. One receptor was located on the roof of Portland Tower which is an 80 m high building in central Manchester. Source receptor distances in the two experiments varied between 120 and 600 m. The results reveal that maximum concentration was sometimes found at roof level rather than at ground level implying the effectiveness of convective forces on dispersion. The degree of vertical dispersion was found to be dependent on source receptor distance as well as on building height in proximity to the release site. Evidence of flow channelling in a street canyon was also found. Both a Gaussian profile and a street network model were applied and the results show that the urban topography may lead to highly effective flow channelling which therefore may be a very important dispersion mechanism should the right meteorological conditions prevail. The experimental results from this campaign have also been compared with a simple urban dispersion model that was developed during the DAPPLE framework and show good agreement with this. The results presented here are some of the first published regarding vertical dispersion. More tracer experiments are needed in order to further characterise vertical concentration profiles and their dependence on, for instance, atmospheric stability. The impact of urban topography on pollutant dispersion is important to focus on in future tracer experiments in order to improve performance of models as well as for our understanding of the relationship between air quality and public health.

  17. CityFlux perfluorocarbon tracer experiments

    Directory of Open Access Journals (Sweden)

    F. K. Petersson

    2010-01-01

    Full Text Available In June 2006, two perfluorocarbon tracer experiments were conducted in central Manchester UK as part of the CityFlux campaign. The main aim was to investigate vertical dispersion in an urban area during convective conditions, but dispersion mechanisms within the street network were also studied. Paired receptors were used in most cases where one receptor was located at ground level and one at roof level. One receptor was located on the roof of Portland Tower which is an 80 m high building in central Manchester. Source receptor distances in the two experiments varied between 120 and 600 m.

    The results reveal that maximum concentration was sometimes found at roof level rather than at ground level implying the effectiveness of convective forces on dispersion. The degree of vertical dispersion was found to be dependent on source receptor distance as well as on building height in proximity to the release site.

    Evidence of flow channelling in a street canyon was also found. Both a Gaussian profile and a street network model were applied and the results show that the urban topography may lead to highly effective flow channelling which therefore may be a very important dispersion mechanism should the right meteorological conditions prevail.

    The experimental results from this campaign have also been compared with a simple urban dispersion model that was developed during the DAPPLE framework and show good agreement with this.

    The results presented here are some of the first published regarding vertical dispersion. More tracer experiments are needed in order to further characterise vertical concentration profiles and their dependence on, for instance, atmospheric stability. The impact of urban topography on pollutant dispersion is important to focus on in future tracer experiments in order to improve performance of models as well as for our understanding of the relationship between air quality and public health.

  18. CityFlux perfluorocarbon tracer experiments

    Directory of Open Access Journals (Sweden)

    F. K. Petersson

    2010-07-01

    Full Text Available In June 2006, two perfluorocarbon tracer experiments were conducted in central Manchester UK as part of the CityFlux campaign. The main aim was to investigate vertical dispersion in an urban area during convective conditions, but dispersion mechanisms within the street network were also studied. Paired receptors were used in most cases where one receptor was located at ground level and one at roof level. One receptor was located on the roof of Portland Tower which is an 80 m high building in central Manchester. Source receptor distances in the two experiments varied between 120 and 600 m.

    The results reveal that maximum concentration was sometimes found at roof level rather than at ground level implying the effectiveness of convective forces on dispersion. The degree of vertical dispersion was found to be dependent on source receptor distance as well as on building height in proximity to the release site.

    Evidence of flow channelling in a street canyon was also found. Both a Gaussian profile and a street network model were applied and the results show that the urban topography may lead to highly effective flow channelling which therefore may be a very important dispersion mechanism should the right meteorological conditions prevail.

    The experimental results from this campaign have also been compared with a simple urban dispersion model that was developed during the DAPPLE framework and show good agreement with this.

    The results presented here are some of the first published regarding vertical dispersion. More tracer experiments are needed in order to further characterise vertical concentration profiles and their dependence on, for instance, atmospheric stability. The impact of urban topography on pollutant dispersion is important to focus on in future tracer experiments in order to improve performance of models as well as for our understanding of the relationship between air quality and public health.

  19. Synthesis of kaempferide Mannich base derivatives and their antiproliferative activity on three human cancer cell lines.

    Science.gov (United States)

    Nguyen, Van-Son; Shi, Ling; Luan, Fang-Qian; Wang, Qiu-An

    2015-01-01

    Kaempferide (3,5,7-trihydroxy-4'-methoxyflavone, 1), a naturally occurring flavonoid with potent anticancer activity in a number of human tumour cell lines, was first semisynthesized from naringin. Based on Mannich reaction of kaempferide with various secondary amines and formaldehyde, nine novel kaempferide Mannich base derivatives 2-10 were synthesized. The aminomethylation occurred preferentially in the position at C-6 and C-8 of the A-ring of kaempferide. All the synthetic compounds were tested for antiproliferative activity against three human cancer cell lines (Hela, HCC1954, SK-OV-3) by the standard MTT method. The results showed that compounds 1, 2 and 5-10 were more potent against Hela cells with IC50 values of 12.47-28.24 μM than the positive control cis-platin (IC50 41.25 μM), compounds 5, 6, 8 and 10 were more potent against HCC1954 cells with IC50 values of 8.82-14.97 μM than the positive control cis-platin (IC50 29.68 μM), and compounds 2, 3, 5, 6 and 10 were more potent against SK-OV-3 cells with IC50 values of 7.67-18.50 μM than the positive control cis-platin (IC50 21.27 μM).

  20. Synthesis and characterization of a HAp-based biomarker with controlled drug release for breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    González, Maykel [Dept. of Molecular Engineering of Materials, Center of Applied Physics and Advanced Technology, National Autonomous University of Mexico (CFATA-UNAM), Boulevard Juriquilla 3001, Santiago de Querétaro, Querétaro 76230 (Mexico); Merino, Ulises [Dept. of Molecular Engineering of Materials, Center of Applied Physics and Advanced Technology, National Autonomous University of Mexico (CFATA-UNAM), Boulevard Juriquilla 3001, Santiago de Querétaro, Querétaro 76230 (Mexico); University of the Valley of Mexico (UVM), Boulevard Villas del Mesón 1000, Juriquilla, Santiago de Querétaro, Querétaro 76320 (Mexico); Vargas, Susana [Dept. of Molecular Engineering of Materials, Center of Applied Physics and Advanced Technology, National Autonomous University of Mexico (CFATA-UNAM), Boulevard Juriquilla 3001, Santiago de Querétaro, Querétaro 76230 (Mexico); Quintanilla, Francisco [University of the Valley of Mexico (UVM), Boulevard Villas del Mesón 1000, Juriquilla, Santiago de Querétaro, Querétaro 76320 (Mexico); Rodríguez, Rogelio, E-mail: rogelior@unam.mx [Dept. of Molecular Engineering of Materials, Center of Applied Physics and Advanced Technology, National Autonomous University of Mexico (CFATA-UNAM), Boulevard Juriquilla 3001, Santiago de Querétaro, Querétaro 76230 (Mexico)

    2016-04-01

    A biocompatible hybrid porous polymer–ceramic material was synthesized to be used as a biomarker in the treatment of breast cancer. This device was equipped with the capacity to release medicaments locally in a controlled manner. The biomaterial was Hydroxyapatite(HAp)-based and had a controlled pore size and pore volume fraction. It was implemented externally using a sharp end and a pair of barbed rings placed opposite each other to prevent relative movement once implanted. The biomarker was impregnated with cis-diamine dichloride platinum (II) [Cl{sub 2}-Pt-(NH{sub 3}){sub 2}]; the rate of release was obtained using inductively coupled plasma atomic emission spectroscopy (ICP-AES), and release occurred over the course of three months. Different release profiles were obtained as a function of the pore volume fraction. The biomaterial was characterized using scanning electron microscopy (SEM) and Raman spectroscopy. - Highlights: • A novel biocompatible hybrid porous polymer–ceramic material was synthesized. • The polymer–ceramic (HAp-based) material was used to prepare a biomarker. • The biomarker was impregnated with cis-diamine dichloride platinum (II). • The rate of cisplatin release was determined using inductively coupled plasma. • The kinetics of the cisplatin release was studied varying the biomarker porosity.

  1. Synthesis and Biological Activity of 6-Selenocaffeine: Potential Modulator of Chemotherapeutic Drugs in Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Inês L. Martins

    2013-05-01

    Full Text Available We report the development of a new microwave-based synthetic methodology mediated by Woollins’ reagent that allowed an efficient conversion of caffeine into 6-selenocaffeine. A preliminary evaluation on the modulation of antioxidant activity upon selenation of caffeine, using the DPPH assay, indicated a mild antioxidant activity for 6-selenocaffeine, contrasting with caffeine, that exhibited no antioxidant activity under the same experimental conditions. Interestingly, whereas 6-selenocaffeine has revealed to have a low cytotoxic potential in both MCF10A and MCF-7 breast cells (24 h, up to 100 µM, MTT assay, a differential effect was observed when used in combination with the anticancer agents doxorubicin and oxaliplatin in MCF-7 breast cancer cells. The co-treatment of doxorubicin (1 µM and 6-selenocaffeine (100 µM resulted in a slight decrease in cellular viability when compared to doxorubicin (1 µM alone. Conversely, the seleno-caffeine derivative at the same concentration markedly increased the viability of oxaliplatin (100 µM-treated cells (p < 0.01. Overall, this work highlights an emerging methodology to synthesize organoselenium compounds and points out the differential roles of 6-selenocaffeine in the modulation of the cytotoxicity of anticancer agents.

  2. Detection of tracer materials in the atmosphere

    Energy Technology Data Exchange (ETDEWEB)

    Jenkins, A.; Lovelock, J.E.

    1981-12-08

    As oxygen is an electron absorber it is desirable, when monitoring an atmospheric flow for the presence of tracer materials capable of detection in an electron capture detector, to remove the oxygen from the flow to the detector. The invention introduces a hydrogen supply directly into the atmospheric flow to allow the hydrogen to combine catalytically with the oxygen content of the flow to form water or water vapor. The thus formed water or water vapor is extracted from the flow proceeding to the detector. The reaction can occur within a palladium or palladium alloy conduit forming a part of the flow path to the detector.

  3. Tracer Dispersion in a Multi-compartment Structure

    CERN Document Server

    Skvortsov, A; Gamble, G; Roberts, M; Ilaya, O; Pitaliadda, D

    2012-01-01

    An experimental study of the tracer dispersion in a complex structure is presented. A point source of tracer (dyed salt) was placed inside a multi-compartment structure embedded in water tank. This experimental setting corresponds to a hazardous tracer release inside the engineering structure (building, ship, aircarft etc). A system of conductivity sensors was deployed to monitor the propagation of a tracer plume in the structure, including tracer trapping inside some compartments and its release to the outside environment through the external openings. The experimental data is processed by employing the ideas of scaling and self-similarity of underlying transport processes. The established and validated scaling laws provide a rigorous way to up-scale the results of laboratory modeling to real operational scenarios and can be used as an important step in the development of risk-assessment models for the first responders to hazardous releases. Keywords: hazardous plume, tracer dispersion, diffusion and advecti...

  4. Multi Resolution AHB Bus Tracer with Real Time Compression for SOC

    Directory of Open Access Journals (Sweden)

    J. Jagadish Reddy

    2013-01-01

    Full Text Available AMBA (Advanced Microcontroller based Bus Architecture consists of AHB, APB, ASB and AXI. In this project we are Tracing AHB (Advanced High performance Bus signals with Real time Compression and Multi-resolution Techniques. A simple transaction on the AHB consists of an address phase and a subsequent data phase. Access to the target device is controlled through a MUX , thereby admitting bus-access to one bus-master at a time. In AHB Tracer we have to Trace Address signals, Data signals and Control signals, we have to compress them depending on AHB protocols. A multi-resolution AHB on-chip bus tracer is named as SYS_HMRBT (AHB Multi-resolution Bus Tracer and is used for monitoring. The goal is to provide better compression quality and multiple resolution traces to meet the complex SoC debugging needs. Compressing all signals at cycle-accurate-level does not always meet the debugging needs. As SOCs become more complex, the transaction level debugging becomes increasingly important, since it helps designers focus on the functional behaviors, instead of interpreting complex signals. By using this SYS_HMRBT, we can achieve 79%-96% of compression depending on selected resolution mode. Tools Used for this Project are Modelsim for Simulation, and Xilinx ISE II for Synthesis

  5. Compilation and analyses of results from cross-hole tracer tests with conservative tracers

    Energy Technology Data Exchange (ETDEWEB)

    Hjerne, Calle; Nordqvist, Rune; Harrstroem, Johan (Geosigma AB (Sweden))

    2010-09-15

    Radionuclide transport in hydrogeological formations is one of the key factors for the safety analysis of a future repository of nuclear waste. Tracer tests have therefore been an important field method within the SKB investigation programmes at several sites since the late 1970's. This report presents a compilation and analyses of results from cross-hole tracer tests with conservative tracers performed within various SKB investigations. The objectives of the study are to facilitate, improve and reduce uncertainties in predictive tracer modelling and to provide supporting information for SKB's safety assessment of a final repository of nuclear waste. More specifically, the focus of the report is the relationship between the tracer mean residence time and fracture hydraulic parameters, i.e. the relationship between mass balance aperture and fracture transmissivity, hydraulic diffusivity and apparent storativity. For 74 different combinations of pumping and injection section at six different test sites (Studsvik, Stripa, Finnsjoen, Aespoe, Forsmark, Laxemar), estimates of mass balance aperture from cross-hole tracer tests as well as transmissivity were extracted from reports or in the SKB database Sicada. For 28 of these combinations of pumping and injection section, estimates of hydraulic diffusivity and apparent storativity from hydraulic interference tests were also found. An empirical relationship between mass balance aperture and transmissivity was estimated, although some uncertainties for individual data exist. The empirical relationship between mass balance aperture and transmissivity presented in this study deviates considerably from other previously suggested relationships, such as the cubic law and transport aperture as suggested by /Dershowitz and Klise 2002/, /Dershowitz et al. 2002/ and /Dershowitz et al. 2003/, which also is discussed in this report. No clear and direct empirical relationship between mass balance aperture and hydraulic

  6. An alternative and expedient synthesis of radioiodinated 4-iodophenylalanine

    Energy Technology Data Exchange (ETDEWEB)

    Vaidyanathan, Ganesan, E-mail: ganesan.v@duke.edu [Department of Radiology, Box 3808, Duke University Medical Center, Durham, NC 27710 (United States); McDougald, Darryl; Grasfeder, Linda; Zalutsky, Michael R.; Chin, Bennett [Department of Radiology, Box 3808, Duke University Medical Center, Durham, NC 27710 (United States)

    2011-10-15

    Radiolabeled amino acids have been used extensively in oncology both as diagnostic and therapeutic agents. In our pursuit to develop radiopharmaceuticals to target breast cancer, we were interested in determining the uptake of radioiodinated 4-iodophenylalanine, among other labeled amino acids, in breast cancer cells. In this work, we have developed an alternative method for the synthesis of this agent. The novel tin precursor, (S)-tert-butyl 2-(tert-butoxycarbonylamino)-3-(4-(tributylstannyl)phenyl)propanoate (3) was synthesized from the known, corresponding iodo derivative. Initially, the labeled 4-iodophenylalanine was synthesized from the above tin precursor in two steps with radiochemical yields of 91.6{+-}2.7% and 83.7{+-}1.7% (n=5), for the radioiodination (first) and deprotection (second) step, respectively. Subsequently, it was synthesized in a single step with an average radiochemical yield of 94.8{+-}3.4% (n=5). After incubation with MCF-7 breast cancer cells for 60 min, an uptake of up to 49.0{+-}0.7% of the input dose was seen; in comparison, the uptake of [{sup 14}C]phenylalanine under the same conditions was 55.9{+-}0.5%. Furthermore, the uptake of both tracers was inhibited to a similar degree in a concentration-dependent manner by both unlabeled phenylalanine and 4-iodophenylalanine. With [{sup 14}C]phenylalanine as the tracer, IC{sub 50} values of 1.45 and 2.50 mM were obtained for Phe and I-Phe, respectively, and these values for [{sup 125}I]I-Phe inhibition were 1.3 and 1.0 mM. In conclusion, an improved and convenient method for the synthesis of no-carrier-added 4-[{sup *}I]phenylalanine was developed and the radiotracer prepared by this route demonstrated an amino acid transporter-mediated uptake in MCF-7 breast cancer cells in vitro that was comparable to that of [{sup 14}C]phenylalanine. - Highlights: > A new method to synthesize radioiodinated 4-iodophenylalanine. > Acid-labile protecting groups containing tin precursor. > Efficient removal

  7. How to chase a tracer - combining conventional salt tracer testing and direct push electrical conductivity profiling for enhanced aquifer characterization

    Science.gov (United States)

    Vienken, Thomas; Huber, Emanuel; Kreck, Manuel; Huggenberger, Peter; Dietrich, Peter

    2017-01-01

    Tracer testing is a well-established technique in hydrogeological site characterization. However, certain a priori knowledge of the hydraulic regime is required beforehand to avoid test failure, e.g. miss of tracer. In this study, we propose a novel tracer test concept for the hydraulic characterization of shallow unconsolidated sedimentary deposits when only scarce a priori information on the hydraulic regime is available. Therefore, we combine conventional salt tracer testing with direct push vertical high resolution electrical conductivity logging. The proposed tracer test concept was successfully tested on coarse, braided river deposits of the Tagliamento River, Italy. With limited a priori information available two tracer tests were performed in three days to reliably determine ground water flow direction and velocity allowing on-site decision-making to adaptively install observation wells for reliable breakthrough curve measurements. Furthermore, direct push vertical electrical profiling provided essential information about the plume characteristics with outstanding measurement resolution and efficiency.

  8. A single food bolus stimulates albumin synthesis in growing piglets

    NARCIS (Netherlands)

    de Meer, K; Smolders, HC; Meesterburrie, J; de Sain-van der Velden, M; Voorbij, HAM; Okken, A; Reijngoud, DJ; Kulik, W

    2000-01-01

    Background: A stable isotope tracer method to quantify the synthesis of proteins of hepatic origin in response to feeding is described. The response of albumin synthesis on one mixed meal in a piglet model was investigated and the intragastric and intravenous administration modes of C-13-valine were

  9. Fibroblasts from patients with Diamond-Blackfan anaemia show abnormal expression of genes involved in protein synthesis, amino acid metabolism and cancer

    Directory of Open Access Journals (Sweden)

    Ramenghi Ugo

    2009-09-01

    Full Text Available Abstract Background Diamond-Blackfan anaemia (DBA is a rare inherited red cell hypoplasia characterised by a defect in the maturation of erythroid progenitors and in some cases associated with malformations. Patients have an increased risk of solid tumors. Mutations have been found in several ribosomal protein (RP genes, i.e RPS19, RPS24, RPS17, RPL5, RPL11, RPL35A. Studies in haematopoietic progenitors from patients show that haplo-insufficiency of an RP impairs rRNA processing and ribosome biogenesis. DBA lymphocytes show reduced protein synthesis and fibroblasts display abnormal rRNA processing and impaired proliferation. Results To evaluate the involvement of non-haematopoietic tissues in DBA, we have analysed global gene expression in fibroblasts from DBA patients compared to healthy controls. Microarray expression profiling using Affymetrix GeneChip Human Genome U133A 2.0 Arrays revealed that 421 genes are differentially expressed in DBA patient fibroblasts. These genes include a large cluster of ribosomal proteins and factors involved in protein synthesis and amino acid metabolism, as well as genes associated to cell death, cancer and tissue development. Conclusion This analysis reports for the first time an abnormal gene expression profile in a non-haematopoietic cell type in DBA. These data support the hypothesis that DBA may be due to a defect in general or specific protein synthesis.

  10. 腹腔镜直肠癌根治术中应用纳米炭示踪剂对免疫及肝肾功能的影响%Effects of the nano carbon tracer on immunologic and hepatorenal functions in patients with the surgery of laparoscopic colorectal cancer radical prostatectomy

    Institute of Scientific and Technical Information of China (English)

    田相安; 丁元升; 杨成菊; 孙钦立

    2016-01-01

    Objective:To study the impact of nano carbon tracer on immunologic and hepatorenal functions in pa-tients with the surgery of laparoscopic colorectal cancer radical prostatectomy.Methods:By the principal of randomi-zation,60 patients with colorectal cancer were divided into two groups,30 cases in each.The nano group patients were injected nano carbon suspension injection through anal before the surgery.While the control group patients with no in-tervention.After that two groups were treated by the same principle of the operation.The level of CD3 +,CD4 +, CD8 +,CD4 +/CD8 +,the hepatorenal function were measured before and 1st,3rd,5th,7th after the operation.Re-sults:The immunologic function indicators of two groups were both degraded 24 hours after operation,where as nano group was significantly fallen.The abnormalities of immunologic function indicators started to rise from the 3rd day and returned to normal levels on the 5th day in the control group.While the nano group was elevated from 5th day and restored to normal on the 7th day.The serum AST,ALT,BUN and Cr were all in the normal range(P >0.05).In nano group,the immune function recovery time was longer compared with the control group.Conclusion:In applica-tion of laparoscopic surgery nano carbon tracer has a transient inhibition to the human immunologic function,it has no effects on liver and kidney function.%目的:探讨纳米炭示踪剂在腹腔镜直肠癌根治术中对机体免疫功能及肝肾功能的影响。方法:按照随机化原则将60例直肠癌患者分为纳米炭组和对照组,纳米炭组30例于术前经肛门注射纳米炭混悬注射液,对照组30例不注射纳米炭混悬注射液。两组均由同组手术医师按相同手术原则行腹腔镜辅助下直肠癌根治术。分别测定术前1天和术后第1、3、5、7天肝肾功、CD3+细胞、CD4+细胞、CD8+细胞、CD4+/CD8+比值并进行对比。结果:与术前1天相比,术后第1 天两组免

  11. Urban Pollutant Transport and Infiltration into Buildings Using Perfluorocarbon Tracers.

    Science.gov (United States)

    Matthews, James C; Bacak, Asan; Khan, M Anwar H; Wright, Matthew D; Priestley, Michael; Martin, Damien; Percival, Carl J; Shallcross, Dudley E

    2017-02-21

    People spend the majority of their time indoors and therefore the quality of indoor air is worthy of investigation; indoor air quality is affected by indoor sources of pollutants and from pollutants entering buildings from outdoors. In this study, unique perfluorocarbon tracers were released in five experiments at a 100 m and ~2 km distance from a large university building in Manchester, UK and tracer was also released inside the building to measure the amount of outdoor material penetrating into buildings and the flow of material within the building itself. Air samples of the tracer were taken in several rooms within the building, and a CO₂ tracer was used within the building to estimate air-exchange rates. Air-exchange rates were found to vary between 0.57 and 10.90 per hour. Indoor perfluorocarbon tracer concentrations were paired to outdoor tracer concentrations, and in-out ratios were found to vary between 0.01 and 3.6. The largest room with the lowest air-exchange rate exhibited elevated tracer concentrations for over 60 min after the release had finished, but generally had the lowest concentrations, the room with the highest ventilation rates had the highest concentration over 30 min, but the peak decayed more rapidly. Tracer concentrations indoors compared to outdoors imply that pollutants remain within buildings after they have cleared outside, which must be considered when evaluating human exposure to outdoor pollutants.

  12. On the linearity of tracer bias around voids

    CERN Document Server

    Pollina, Giorgia; Dolag, Klaus; Weller, Jochen; Baldi, Marco; Moscardini, Lauro

    2016-01-01

    The large-scale structure of the universe can only be observed directly via luminous tracers of the underlying distribution of dark matter. However, the clustering statistics of tracers are biased and depend on various properties of the tracers themselves, such as their host-halo mass and formation and assembly history. On very large scales, where density fluctuations are within the linear regime, this tracer bias results in a constant offset in the clustering amplitude, which is known as linear bias. Towards smaller non-linear scales, this is no longer the case and tracer bias becomes a complicated function of scale and time. We focus on tracer bias centered on cosmic voids, depressions of the density field that spatially dominate the universe. We consider three different types of tracers: galaxies, galaxy clusters and AGNs, extracted from the hydrodynamical simulation suite Magneticum Pathfinder. In contrast to common clustering statistics that focus on the auto-correlation of tracers, we find that void-tra...

  13. Urban Pollutant Transport and Infiltration into Buildings Using Perfluorocarbon Tracers

    Science.gov (United States)

    Matthews, James C.; Bacak, Asan; Khan, M. Anwar H.; Wright, Matthew D.; Priestley, Michael; Martin, Damien; Percival, Carl J.; Shallcross, Dudley E.

    2017-01-01

    People spend the majority of their time indoors and therefore the quality of indoor air is worthy of investigation; indoor air quality is affected by indoor sources of pollutants and from pollutants entering buildings from outdoors. In this study, unique perfluorocarbon tracers were released in five experiments at a 100 m and ~2 km distance from a large university building in Manchester, UK and tracer was also released inside the building to measure the amount of outdoor material penetrating into buildings and the flow of material within the building itself. Air samples of the tracer were taken in several rooms within the building, and a CO2 tracer was used within the building to estimate air-exchange rates. Air-exchange rates were found to vary between 0.57 and 10.90 per hour. Indoor perfluorocarbon tracer concentrations were paired to outdoor tracer concentrations, and in-out ratios were found to vary between 0.01 and 3.6. The largest room with the lowest air-exchange rate exhibited elevated tracer concentrations for over 60 min after the release had finished, but generally had the lowest concentrations, the room with the highest ventilation rates had the highest concentration over 30 min, but the peak decayed more rapidly. Tracer concentrations indoors compared to outdoors imply that pollutants remain within buildings after they have cleared outside, which must be considered when evaluating human exposure to outdoor pollutants. PMID:28230812

  14. Tracer studies of nitrogen assimilation in yeast.

    Science.gov (United States)

    ABRAMS, R; HAMMARSTEN, E

    1949-01-01

    By using N(15) as a tracer the assimilation of ammonia by the yeast, Torulopsis utilis, has been studied. It has been shown that: 1. There was no measurable incorporation of N in the protein or polynucleotide purine of carbon-starved yeast. 2. When ammonia is added to nitrogen-starved yeast there is a long lag period before division begins during which the yeast rapidly synthesizes protein, this process being accompanied by a turnover of polynucleotide purine. There was no significant dilution of the N(15)H(4) (+) of the medium by ordinary NH(4) (+). 3. When yeast containing N(15) is allowed to divide and grow in ordinary ammonia, the total amount of N(15) in the yeast remains constant. The dicarboxylic amino acids are most diluted, while arginine and nucleic acid guanine are not diluted at all.

  15. Elemental tracers for Chinese source dust

    Institute of Scientific and Technical Information of China (English)

    张小曳; 张光宇; 朱光华; 张德二; 安芷生; 陈拓; 黄湘萍

    1996-01-01

    The mass-particle size distributions of 10 dust-carrying elements in aerosol particles were determined tor 12 sites in desert regions of northern China. The desert dust is proved to he of origin of eolian loess deposited on the Loess Plateau. Their transport to the loess was mainly attributable to the non-dust storm processes under the interglacial climate condition. The impact ot" dust storm on the accumulation of the loess increased in the glacial stage. On the basis of the signatures of 4 dust elements (Al. Fe, Mg and Sc). Chinese dust is believed to have 3 major desert sources (northwestern deserts, northern high dust deserts and northern low dust deserts). With a chemical element balance model, an elemental tracer system is established to proportion the export of China-source dust.

  16. Star clusters as tracers of galaxy evolution

    CERN Document Server

    Konstantopoulos, Iraklis S

    2009-01-01

    Star clusters represent the most common 'mode' of star formation. They are found in all types of environments, cascading down from galaxy groups and merging pairs through starbursts to normal galaxies and dwarves and even isolated regions in extragalactic space. As they maintain a link to the overall star formation in a system, they can be used as tracers of the star formation history of environments located at distances prohibitive to the study of individual stars. This makes them ideally suited to the study of mergers and interactions in galaxy pairs and groups. In this work we present observations of the star cluster populations in the local starburst galaxy M82, post-interaction spiral NGC 6872, the "Antennae" merging pair and two compact groups, "Stephan's Quintet" and HCG 7. In each case, we extract information on the clusters and their hosts using mainly HST photometry and Gemini spectroscopy.

  17. National Biomedical Tracer Facility. Project definition study

    Energy Technology Data Exchange (ETDEWEB)

    Schafer, R.

    1995-02-14

    We request a $25 million government-guaranteed, interest-free loan to be repaid over a 30-year period for construction and initial operations of a cyclotron-based National Biomedical Tracer Facility (NBTF) in North Central Texas. The NBTF will be co-located with a linear accelerator-based commercial radioisotope production facility, funded by the private sector at approximately $28 million. In addition, research radioisotope production by the NBTF will be coordinated through an association with an existing U.S. nuclear reactor center that will produce research and commercial radioisotopes through neutron reactions. The combined facilities will provide the full range of technology for radioisotope production and research: fast neutrons, thermal neutrons, and particle beams (H{sup -}, H{sup +}, and D{sup +}). The proposed NBTF facility includes an 80 MeV, 1 mA H{sup -} cyclotron that will produce proton-induced (neutron deficient) research isotopes.

  18. Cancer

    Science.gov (United States)

    ... uses a surgical tool to remove the tumor.Mohs' surgery. Layers of cancer cells are removed one ... usually have not been approved by the U.S. Food and Drug Administration (FDA). The medicine may have ...

  19. Methods and systems using encapsulated tracers and chemicals for reservoir interrogation and manipulation

    Energy Technology Data Exchange (ETDEWEB)

    Roberts, Jeffery; Aines, Roger D; Duoss, Eric B; Spadaccini, Christopher M

    2014-11-04

    An apparatus, method, and system of reservoir interrogation. A tracer is encapsulating in a receptacle. The receptacle containing the tracer is injected into the reservoir. The tracer is analyzed for reservoir interrogation.

  20. Design, synthesis, and anti-breast cancer evaluation of new triarylethylene analogs bearing short alkyl- and polar amino-/amido-ethyl chains.

    Science.gov (United States)

    Kaur, Gurleen; Mahajan, Mohinder P; Pandey, Manoj K; Singh, Parvesh; Ramisetti, Srinivasa R; Sharma, Arun K

    2016-04-15

    The synthesis of novel triarylethylene analogs, designed based on well-known Selective Estrogen Receptor Modulators (SERMs), i.e., ospemifene and tamoxifen, as potential anti-breast cancer agents is described. The cytotoxic potential of these analogs against ER-positive (MCF-7) and ER-negative (MDA-MB-231) human breast cancer cell lines was determined and compared with the standards, ospemifene and tamoxifen. In initial screening, analogs 5, 14 and 15 were found to be much more effective than the standards against both the cell lines. The results showed that these novel analogs inhibit the expression of proteins involved in the migration and metastasis, compound 5 being most effective. Compound 5 inhibited the expression of MMP-9, c-Myc and Caveolin in both MCF-7 and MDA-MB-231 cells, and suppressed the invasion of ER-negative cells in a dose dependent manner. Finally, in silico docking simulations of the representative compounds in the binding sites of the estrogen receptors (ERs) indicated a good binding affinity of the compounds with the ERs, and supported their experimental toxicity against MCF-7 cancer cell lines.

  1. Pharmacologic inhibition of the CK2-mediated phosphorylation of B23/NPM in cancer cells selectively modulates genes related to protein synthesis, energetic metabolism, and ribosomal biogenesis.

    Science.gov (United States)

    Perera, Yasser; Pedroso, Seidy; Borras-Hidalgo, Orlando; Vázquez, Dania M; Miranda, Jamilet; Villareal, Adelaida; Falcón, Viviana; Cruz, Luis D; Farinas, Hernán G; Perea, Silvio E

    2015-06-01

    B23/NPM is a multifunctional nucleolar protein frequently overexpressed, mutated, or rearranged in neoplastic tissues. B23/NPM is involved in diverse biological processes and is mainly regulated by heteroligomer association and posttranslational modification, phosphorylation being a major posttranslational event. While the role of B23/NPM in supporting and/or driving malignant transformation is widely recognized, the particular relevance of its CK2-mediated phosphorylation remains unsolved. Interestingly, the pharmacologic inhibition of such phosphorylation event by CIGB-300, a clinical-grade peptide drug, was previously associated to apoptosis induction in tumor cell lines. In this work, we sought to identify the biological processes modulated by CIGB-300 in a lung cancer cell line using subtractive suppression hybridization and subsequent functional annotation clustering. Our results indicate that CIGB-300 modulates a subset of genes involved in protein synthesis (ES = 8.4, p NPM in cancer cells, revealing at the same time the potentialities of its pharmacological manipulation for cancer therapy. Finally, this work also suggests several candidate gene biomarkers to be evaluated during the clinical development of the anti-CK2 peptide CIGB-300.

  2. FADS2 function loss at the cancer hotspot 11q13 locus diverts lipid signaling precursor synthesis to unusual eicosanoid fatty acids.

    Directory of Open Access Journals (Sweden)

    Woo Jung Park

    Full Text Available BACKGROUND: Genes coding for the fatty acid desaturases (FADS1, 2, 3 localized at the cancer genomic hotspot 11q13 locus are required for the biosynthesis of 20 carbon polyunsaturated fatty acids (PUFA that are direct eicosanoid precursors. In several cancer cell lines, FADS2 encoded Δ6 and Δ8 desaturation is not functional. METHODOLOGY/PRINCIPAL FINDINGS: Analyzing MCF7 cell fatty acids with detailed structural mass spectrometry, we show that in the absence of FADS2 activity, the FADS1 product Δ5-desaturase operates to produce 5,11,14-20∶3 and 5,11,14,17-20∶4. These PUFA are missing the 8-9 double bond of the eicosanoid signaling precursors arachidonic acid (5,8,11,14-20∶4 and eicosapentaenoic acid (5,8,11,14,17-20∶5. Heterologous expression of FADS2 restores Δ6 and Δ8-desaturase activity and normal eicosanoid precursor synthesis. CONCLUSIONS/SIGNIFICANCE: The loss of FADS2-encoded activities in cancer cells shuts down normal PUFA biosynthesis, deleting the endogenous supply of eicosanoid and downstream docosanoid precursors, and replacing them with unusual butylene-interrupted fatty acids. If recapitulated in vivo, the normal eicosanoid and docosanoid cell signaling milieu would be depleted and altered due to reduction and substitution of normal substrates with unusual substrates, with unpredictable consequences for cellular communication.

  3. Tuning surface coatings of optimized magnetite nanoparticle tracers for in vivo Magnetic Particle Imaging.

    Science.gov (United States)

    Khandhar, Amit P; Ferguson, R Matthew; Arami, Hamed; Kemp, Scott J; Krishnan, Kannan M

    2015-02-01

    Surface coatings are important components of Magnetic Particle Imaging (MPI) tracers - they preserve their key properties responsible for optimum tracer performance in physiological environments. In vivo, surface coatings form a physical barrier between the hydrophobic SPION cores and the physiological environment, and their design dictates the blood half-life and biodistribution of MPI tracers. Here we show the effect of tuning poly(ethylene glycol) (PEG)-based surface coatings on both in vitro and in vivo (mouse model) MPI performance of SPIONs. Our results showed that varying PEG molecular weight had a profound impact on colloidal stability, characterized using Dynamic Light Scattering (DLS), and the m'(H) response of SPIONs, measured in a 25 kHz/20 mTμ0(-1)max Magnetic Particle Spectrometer (MPS). Increasing PEG molecular weight from 5 kDa to 20 kDa preserved colloidal stability and m'(H) response of ~25 nm SPIONs - the optimum core diameter for MPI - in serum-rich cell culture medium for up to 24 hours. Furthermore, we compared the in vivo circulation time of SPIONs as a function of hydrodynamic diameter and showed that clustered SPIONs can adversely affect blood half-life; critically, SPIONs with clusters had 5 times shorter blood half-life than individually coated SPIONs. We anticipate that the development of MPI SPION tracers with long blood half-lives have potential not only in vascular imaging applications, but also enable opportunities in molecular targeting and imaging - a critical step towards early cancer detection using the new MPI modality.

  4. Synthesis of new diarylamides with pyrimidinyl pyridine scaffold and evaluation of their anti-proliferative effect on cancer cell lines.

    Science.gov (United States)

    Abdelazem, Ahmed Z; Al-Sanea, Mohammad M; Park, Hyun-Mee; Lee, So Ha

    2016-02-15

    A new series of diarylamides, having a pyrimidinyl pyridine scaffold, was designed and synthesized. The target compounds were synthesized in three steps. A selected group from the target compounds was tested over a panel of 60 cancer cell lines at a single dose concentration of 10 μM, and the most active compound, 5j, was further tested in a five-dose testing mode to determine its IC50 value over the 60 cell lines. In single-dose testing mode, compound 5j showed the highest growth inhibition against the NCI-60 cancer cell lines, while other tested compounds showed a weak to moderate inhibitory activity against a range of different cancer cell lines. In five-dose testing mode, compound 5j showed strong inhibitory activity in micro molar range against many cancer cell lines. Its major activity was against melanoma cancer cell lines. Therefore, compound 5j is a promising hit compound targeting this severe form of cancer.

  5. Role of Protein Synthesis Initiation Factors in Dietary Soy Isoflavone-Mediated Effects on Breast Cancer Progression

    Science.gov (United States)

    2012-03-01

    Manuscript s • Submitted to the Journal of Nutritional Biochemistry (Feb 21, 2012) “The soy isoflavone equol may increase cancer malignancy via upregulation...29] Ko KP, Park SK, Park B et al. Isoflavones from phytoestrogens and gastric cancer risk: a nested case-control study within the Korean...Dietary Soy Isoflavone-Mediated Effects on Breast Cancer Progression. PRINCIPAL INVESTIGATOR: Columba de la Parra Simental CONTRACTING

  6. PET/Computed Tomography in Renal, Bladder, and Testicular Cancer.

    Science.gov (United States)

    Bouchelouche, Kirsten; Choyke, Peter L

    2015-07-01

    Imaging plays an important role in the clinical management of cancer patients. Hybrid imaging with PET/computed tomography (CT) is having a broad impact in oncology, and in recent years PET/CT is beginning to have an impact in urooncology. In both bladder and renal cancers, there is a need to study the efficacy of other tracers than F-18 fluorodeoxyglucose (FDG), particularly tracers with limited renal excretion. Thus, new tracers are being introduced. This review focuses on the clinical role of FDG and other PET agents in renal, bladder, and testicular cancers.

  7. What Influences the Uptake of Information to Prevent Skin Cancer? A Systematic Review and Synthesis of Qualitative Research

    Science.gov (United States)

    Garside, Ruth; Pearson, Mark; Moxham, Tiffany

    2010-01-01

    Skin cancer is an increasing problem in Europe, America and Australasia, although largely preventable by avoiding excessive ultraviolet (UV) exposure. This paper presents the findings of a systematic review of qualitative research about the prevention of skin cancer attributable to UV exposure. The aim is to understand elements that may contribute…

  8. Radionuclide Tracers for Myocardial Perfusion Imaging and Blood Flow Quantification.

    Science.gov (United States)

    deKemp, Robert A; Renaud, Jennifer M; Klein, Ran; Beanlands, Rob S B

    2016-02-01

    Myocardial perfusion imaging is performed most commonly using Tc-99m-sestamibi or tetrofosmin SPECT as well as Rb-82-rubidium or N-13-ammonia PET. Diseased-to-normal tissue contrast is determined by the tracer retention fraction, which decreases nonlinearly with flow. Reduced tissue perfusion results in reduced tracer retention, but the severity of perfusion defects is typically underestimated by 20% to 40%. Compared to SPECT, retention of the PET tracers is more linearly related to flow, and therefore, the perfusion defects are measured more accurately using N-13-ammonia or Rb-82.

  9. Laboratory Testing of Magnetic Tracers for Soil Erosion Measurement*1

    Institute of Scientific and Technical Information of China (English)

    HU Guo-Qing; DONG Yuan-Jie; WANG Hui; QIU Xian-Kui; WANG Yan-Hua

    2011-01-01

    Soil erosion, which includes soil detachment, transport, and deposition, is one of the important dynamic land surface processes. The magnetic tracer method is a useful method for studying soil erosion processes. In this study, five types of magnetic tracers were made with fine soil, fly ash, cement, bentonite, and magnetic powder (reduced iron powder) using the method of disk granulation. The tracers were uniformly mixed with soil and tested in the laboratory using simulated rainfall and inflow experiments to simulate the interrill and rill components of soil erosion, in order to select one or more tracers which could be used to study detachment and deposition by the erosive forces of raindrops and surface flow of water on a slope. The results showed that the five types of magnetic tracers with high magnetic susceptibility and a wide range of sizes had a range of 0.99-1.29 gcm-s in bulk density. In the interrill and rill experiments, the tracers FC1 and FC2 which consisted of fly ash and cement at ratios of 1:1 and 2:1, respectively, were transported in phase with soil particles since the magnetic susceptibility of sediment approximated that of the soil which was uneroded and the slopes of the regression equations between the detachment of sediment and magnetic tracers FC1 and FC2 were very close to the expected value of 20, which was the original soil/tracer ratio. The detachment and deposition on slopes could be accurately reflected by the magnetic susceptibility differences. The change in magnetic susceptibility depended on whether deposition or detachment occurred. However, the tracer FS which consisted of fine soil and the tracers FB1 and FB2 which consisted of fly ash and bentonite at ratios of 1:1 and 2:1, respectively, were all unsuitable for soil erosion study since there was no consistent relationship between sediment and tracer detachment for increasing amounts of runoff. Therefore, the tracers FC1 and FC2 could be used to study soil erosion by water.

  10. Tracer diffusivity and effective temperature in bacterial suspensions

    CERN Document Server

    Patteson, Alison E; Purohit, Prashant K; Arratia, Paulo E

    2015-01-01

    The dynamics of tracer particles in \\textit{E. coli} suspensions are experimentally investigated as a function of particle size and bacteria concentration. We find that tracer diffusivity is enhanced due to particle-bacteria interactions and varies non-monotonically with particle size, exhibiting a peak at sizes comparable to the bacterial length. The time scale characterizing the transition from ballistic to diffusive regime increases monotonically with \\textit{E. coli} concentration and particle size. Diffusivity measurements are then used to estimate suspension effective temperature, which varies nonlinearly with tracer size, suggesting that measures of activity are probe size dependent.

  11. TRACER STUDY OF RTU GRADUATES: AN ANALYSIS

    Directory of Open Access Journals (Sweden)

    Thelma L. Ramirez

    2014-01-01

    Full Text Available This paper aimed to determine if the field of specialization in the different colleges of RTU graduates and their academic-acquired skills and competencies are related to their present occupations. A modified Graduate Tracer Study (GTS instrument was utilized to gather the quantitative data. Out of 500 questionnaires administered, there were 250 graduates returned answered questionnaires representing the three Colleges: Education, Arts and Sciences, Business and Entrepreneurial Technology. A face to face interview was also conducted in order to support the gathered data. The SPSS was used to generate results from the acquired quantitative data using the frequency counts, percentage and the Chi-square goodness of fit test. The findings revealed that the graduates claimed that their knowledge, academic-acquired skills and competencies contributed greatly in their job performance. The Chi-square goodness of fit proved that there is a significant relationship between the graduates’ fields of specialization and their occupations after graduation. Likewise, the academic-acquired skills and competencies of the graduates are relevant to their chosen occupations. The results further proved that RTU produces marketable and appropriately trained graduates with the majority landing in course-related jobs within a short period after graduation. The study also indicates that the RTU graduates possess the skills and competencies necessary to succeed in this competitive world. However eexpansion of tie-ups with private business entities is made to at least maintain the high employability level of the graduates.

  12. National Biomedical Tracer Facility: Project definition study

    Energy Technology Data Exchange (ETDEWEB)

    Heaton, R.; Peterson, E. [Los Alamos National Lab., NM (United States); Smith, P. [Smith (P.A.) Concepts and Designs (United States)

    1995-05-31

    The Los Alamos National Laboratory is an ideal institution and New Mexico is an ideal location for siting the National Biomedical Tracer Facility (NBTF). The essence of the Los Alamos proposal is the development of two complementary irradiation facilities that combined with our existing radiochemical processing hot cell facilities and waste handling and disposal facilities provide a low cost alternative to other proposals that seek to satisfy the objectives of the NBTF. We propose the construction of a 30 MeV cyclotron facility at the site of the radiochemical facilities, and the construction of a 100 MeV target station at LAMPF to satisfy the requirements and objectives of the NBTF. We do not require any modifications to our existing radiochemical processing hot cell facilities or our waste treatment and disposal facilities to accomplish the objectives of the NBTF. The total capital cost for the facility defined by the project definition study is $15.2 M. This cost estimate includes $9.9 M for the cyclotron and associated facility, $2.0 M for the 100 MeV target station at LAMPF, and $3.3 M for design.

  13. Synthesis of Novel β-Keto-Enol Derivatives Tethered Pyrazole, Pyridine and Furan as New Potential Antifungal and Anti-Breast Cancer Agents

    Directory of Open Access Journals (Sweden)

    Smaail Radi

    2015-11-01

    Full Text Available Recently, a new generation of highly promising inhibitors bearing β-keto-enol functionality has emerged. Reported herein is the first synthesis and use of novel designed drugs based on the β-keto-enol group embedded with heterocyclic moieties such as pyrazole, pyridine, and furan, prepared in a one-step procedure by mixed Claisen condensation. All the newly synthesized compounds were characterized by FT-IR, 1H-NMR, 13C-NMR, ESI/LC-MS, elemental analysis, and evaluated for their in vitro antiproliferative activity against breast cancer (MDA-MB241 human cell lines and fungal strains (Fusarium oxysporum f.sp albedinis FAO. Three of the synthesized compounds showed potent activity against fungal strains with IC50 values in the range of 0.055–0.092 µM. The results revealed that these compounds showed better IC50 values while compared with positive controls.

  14. Straightforward synthesis of a novel ring-fused pyrazole-lactam and in vitro cytotoxic activity on cancer cell lines.

    Science.gov (United States)

    Bertuzzi, G; Locatelli, E; Colecchia, D; Calandro, P; Bonini, B F; Chandanshive, J Z; Mazzanti, A; Zani, P; Chiariello, M; Comes Franchini, M

    2016-07-19

    In this paper a straightforward synthesis of a novel pyrazole derivative is reported. Prominent feature of this synthetic process is a 1,3-Dipolar Cycloaddition of a suitable nitrile imine with an activated α,β-unsaturated lactam to afford directly and regioselectively the corresponding ring-fused pyrazole. Having obtained the central core of the synthetic target, a double stepwise functionalization with a "side chain" characterized by a terminal cyclic aliphatic amine was carried out. This molecular structure was designed to interact strongly with typical biological residues, and indeed it showed potent anticancer capability: in vitro cytotoxicity test on five different cancer cell lines showed interesting IC50 values in the range of 15-60 μM for exposure time of 24-72 h, thus resulting comparable with commercially available and nowadays therapeutically exploited anticancer compounds, such as 5-FU and NVP-BEZ235.

  15. A Systematic Method For Tracer Test Analysis: An Example Using Beowawe Tracer Data

    Energy Technology Data Exchange (ETDEWEB)

    G. Michael Shook

    2005-01-01

    Quantitative analysis of tracer data using moment analysis requires a strict adherence to a set of rules which include data normalization, correction for thermal decay, deconvolution, extrapolation, and integration. If done correctly, the method yields specific information on swept pore volume, flow geometry and fluid velocity, and an understanding of the nature of reservoir boundaries. All calculations required for the interpretation can be done in a spreadsheet. The steps required for moment analysis are reviewed in this paper. Data taken from the literature is used in an example calculation.

  16. Analysis of Mammalian Cell Proliferation and Macromolecule Synthesis Using Deuterated Water and Gas Chromatography-Mass Spectrometry

    Directory of Open Access Journals (Sweden)

    Victoria C. Foletta

    2016-10-01

    Full Text Available Deuterated water (2H2O, a stable isotopic tracer, provides a convenient and reliable way to label multiple cellular biomass components (macromolecules, thus permitting the calculation of their synthesis rates. Here, we have combined 2H2O labelling, GC-MS analysis and a novel cell fractionation method to extract multiple biomass components (DNA, protein and lipids from the one biological sample, thus permitting the simultaneous measurement of DNA (cell proliferation, protein and lipid synthesis rates. We have used this approach to characterize the turnover rates and metabolism of a panel of mammalian cells in vitro (muscle C2C12 and colon cancer cell lines. Our data show that in actively-proliferating cells, biomass synthesis rates are strongly linked to the rate of cell division. Furthermore, in both proliferating and non-proliferating cells, it is the lipid pool that undergoes the most rapid turnover when compared to DNA and protein. Finally, our data in human colon cancer cell lines reveal a marked heterogeneity in the reliance on the de novo lipogenic pathway, with the cells being dependent on both ‘self-made’ and exogenously-derived fatty acid.

  17. Rational design, synthesis, and biological evaluation of third generation α-noscapine analogues as potent tubulin binding anti-cancer agents.

    Science.gov (United States)

    Manchukonda, Naresh Kumar; Naik, Pradeep Kumar; Santoshi, Seneha; Lopus, Manu; Joseph, Silja; Sridhar, Balasubramanian; Kantevari, Srinivas

    2013-01-01

    Systematic screening based on structural similarity of drugs such as colchicine and podophyllotoxin led to identification of noscapine, a microtubule-targeted agent that attenuates the dynamic instability of microtubules without affecting the total polymer mass of microtubules. We report a new generation of noscapine derivatives as potential tubulin binding anti-cancer agents. Molecular modeling experiments of these derivatives 5a, 6a-j yielded better docking score (-7.252 to -5.402 kCal/mol) than the parent compound, noscapine (-5.505 kCal/mol) and its existing derivatives (-5.563 to -6.412 kCal/mol). Free energy (ΔG bind ) calculations based on the linear interaction energy (LIE) empirical equation utilizing Surface Generalized Born (SGB) continuum solvent model predicted the tubulin-binding affinities for the derivatives 5a, 6a-j (ranging from -4.923 to -6.189 kCal/mol). Compound 6f showed highest binding affinity to tubulin (-6.189 kCal/mol). The experimental evaluation of these compounds corroborated with theoretical studies. N-(3-brormobenzyl) noscapine (6f) binds tubulin with highest binding affinity (KD, 38 ± 4.0 µM), which is ~ 4.0 times higher than that of the parent compound, noscapine (KD, 144 ± 1.0 µM) and is also more potent than that of the first generation clinical candidate EM011, 9-bromonoscapine (KD, 54 ± 9.1 µM). All these compounds exhibited substantial cytotoxicity toward cancer cells, with IC50 values ranging from 6.7 µM to 72.9 µM; compound 6f showed prominent anti-cancer efficacy with IC50 values ranging from 6.7 µM to 26.9 µM in cancer cells of different tissues of origin. These compounds perturbed DNA synthesis, delayed the cell cycle progression at G2/M phase, and induced apoptotic cell death in cancer cells. Collectively, the study reported here identified potent, third generation noscapinoids as new anti-cancer agents.

  18. Rational design, synthesis, and biological evaluation of third generation α-noscapine analogues as potent tubulin binding anti-cancer agents.

    Directory of Open Access Journals (Sweden)

    Naresh Kumar Manchukonda

    Full Text Available Systematic screening based on structural similarity of drugs such as colchicine and podophyllotoxin led to identification of noscapine, a microtubule-targeted agent that attenuates the dynamic instability of microtubules without affecting the total polymer mass of microtubules. We report a new generation of noscapine derivatives as potential tubulin binding anti-cancer agents. Molecular modeling experiments of these derivatives 5a, 6a-j yielded better docking score (-7.252 to -5.402 kCal/mol than the parent compound, noscapine (-5.505 kCal/mol and its existing derivatives (-5.563 to -6.412 kCal/mol. Free energy (ΔG bind calculations based on the linear interaction energy (LIE empirical equation utilizing Surface Generalized Born (SGB continuum solvent model predicted the tubulin-binding affinities for the derivatives 5a, 6a-j (ranging from -4.923 to -6.189 kCal/mol. Compound 6f showed highest binding affinity to tubulin (-6.189 kCal/mol. The experimental evaluation of these compounds corroborated with theoretical studies. N-(3-brormobenzyl noscapine (6f binds tubulin with highest binding affinity (KD, 38 ± 4.0 µM, which is ~ 4.0 times higher than that of the parent compound, noscapine (KD, 144 ± 1.0 µM and is also more potent than that of the first generation clinical candidate EM011, 9-bromonoscapine (KD, 54 ± 9.1 µM. All these compounds exhibited substantial cytotoxicity toward cancer cells, with IC50 values ranging from 6.7 µM to 72.9 µM; compound 6f showed prominent anti-cancer efficacy with IC50 values ranging from 6.7 µM to 26.9 µM in cancer cells of different tissues of origin. These compounds perturbed DNA synthesis, delayed the cell cycle progression at G2/M phase, and induced apoptotic cell death in cancer cells. Collectively, the study reported here identified potent, third generation noscapinoids as new anti-cancer agents.

  19. Tracking thermal fronts with temperature-sensitive, chemically reactive tracers

    Energy Technology Data Exchange (ETDEWEB)

    Robinson, B.A.; Birdsell, S.A.

    1987-01-01

    Los Alamos is developing tracer techniques using reactive chemicals to track thermal fronts in fractured geothermal reservoirs. If a nonadsorbing tracer flowing from the injection to production well chemically reacts, its reaction rate will be a strong function of temperature. Thus the extent of chemical reaction will be greatest early in the lifetime of the system, and less as the thermal front progresses from the injection to production well. Early laboratory experiments identified tracers with chemical kinetics suitable for reservoirs in the temperature range of 75 to 100/sup 0/C. Recent kinetics studies have focused on the kinetics of hydrolysis of derivatives of bromobenzene. This class of reactions can be used in reservoirs ranging in temperature from 150 to 275/sup 0/C, which is of greater interest to the geothermal industry. Future studies will include laboratory adsorption experiments to identify possibly unwanted adsorption on granite, development of sensitive analytical techniques, and a field demonstration of the reactive tracer concept.

  20. A theoretical framework of tracer methods for marine sediment dynamics

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    A new theoretical framework of tracer methods is proposed in the present contribution, on the basis of mass conservation. This model is applicable for both artificial and natural tracers. It can be used to calculate the spatial distribution patterns of sediment transport rate, thus providing independent information and verification for the results derived from empirical formulae. For the procedures of the calculation, first, the tracer concentration and topographic maps of two times are obtained. Then, the spatial and temporal changes in the concentration and seabed elevation are calculated, and the boundary conditions required are determined by field observations (such as flow and bedform migration measurements). Finally, based upon eqs. (1) and (13), the transport rate is calculated and expressed as a function of the position over the study area. Further, appropriate modifications to the model may allow the tracer to have different densities and grain size distributions from the bulk sediment.

  1. Tracer dispersion in a percolation network with spatial correlations

    Science.gov (United States)

    Makse; Andrade; Eugene Stanley H

    2000-01-01

    We analyze the transport properties of a neutral tracer in a carrier fluid flowing through percolationlike porous media with spatial correlations. We model convection in the mass transport process using the velocity field obtained by the numerical solution of the Navier-Stokes and continuity equations in the pore space. We find that the resulting statistical properties of the tracer show a transition from a subdiffusion regime at low Peclet number to an enhanced diffusion regime at high Peclet number.

  2. Mobility of Metal Tracers in Unsaturated Tuffs of Busted Butte

    Science.gov (United States)

    Groffman, A. R.

    2001-12-01

    A complex tracer mixture was injected continuously for over two years into a 10 m x 10 m x 7 m block of unsaturated tuff as part of the Busted Butte unsaturated-zone tracer test at Yucca Mountain. The test was designed to measure tracer transport within the Topopah Springs and Calico Hills tuffs, units that occur between the potential high-level nuclear waste repository at Yucca Mountain and the water table below. The mixture included nonreactive (Br, I, and fluorinated benzoic acids (FBAs)) and reactive tracers (Li, Ce, Sm, Ni, Co, and Mn). Bromide, I, FBAs, and Li were detected during the test on absorbent pads emplaced in a series of solute collection boreholes located beneath the injectors but the more strongly sorbing metals did not reach the collection boreholes during this period. To determine the distribution and mobility of these metals, tracer constituents were extracted from tuff samples collected during overcoring and mineback of the test block. Tracers were extracted from the tuff samples by leaching with a 5% nitric acid solution for metals and a bicarbonate-carbonate buffer for anions. Results from the overcore sample suite show that metals have migrated through the tuff in the region adjacent to and immediately below the tracer injectors. Consistent with laboratory sorption measurements and observed breakthrough in the collection boreholes, rock analyses showed that Li is the most mobile of the metals. Co and Ni behave similarly, traveling tens of cm from the injection sites, while Sm and Ce moved far less, possibly due to precipitation reactions in addition to sorption. Determination of Mn transport is complicated by high background concentrations in the tuff; additional background samples are currently being evaluated. As expected, our rock analyses show that the nonreactive tracers Br and FBAs have moved beyond the overcore region, corroborating results from collection boreholes.

  3. Assessment of Halon-1301 as a groundwater age tracer

    OpenAIRE

    M. Beyer; R. van der Raaij; U. Morgenstern; Jackson, B.(Department of Physics, University of Pennsylvania, Philadelphia, PA, United States)

    2015-01-01

    Groundwater dating is an important tool to assess groundwater resources in regards to their dynamics, i.e. direction and timescale of groundwater flow and recharge, contamination risks and manage remediation. To infer groundwater age information, a combination of different environmental tracers, such as tritium and SF6, are commonly used. However, ambiguous age interpretations are often faced, due to a limited set of available tracers and their individual restricted applicat...

  4. Assessment of Halon-1301 as a groundwater age tracer

    OpenAIRE

    M. Beyer; R. van der Raaij; U. Morgenstern; Jackson, B.(Department of Physics, University of Pennsylvania, Philadelphia, PA, United States)

    2015-01-01

    Groundwater dating is an important tool to assess groundwater resources in regards to their dynamics, i.e. direction and time scale of groundwater flow and recharge, to assess contamination risks and manage remediation. To infer groundwater age information, a combination of different environmental tracers, such as tritium and SF6, are commonly used. However, ambiguous age interpretations are often faced, due to a limited set of available tracers and their in...

  5. Energy spectra and passive tracer cascades in turbulent flows

    CERN Document Server

    Jolly, Michael

    2016-01-01

    We study the influence of the energy spectrum on the extent of the cascade range of a passive tracer in turbulent flows. The interesting cases are when there are two different spectra over the potential range of the tracer cascade (in 2D when the tracer forcing is in the inverse energy cascade range, and in 3D when the Schmidt number Sc is large). The extent of the tracer cascade range is then limited by the width of the range for the shallower of the two energy spectra. Nevertheless, we show that in dimension $d=2,3$ the tracer cascade range extends (up to a logarithm) to $\\kappa_{d\\text{D}}^{p}$, where $\\kappa_{d\\text{D}}$ is the wavenumber beyond which diffusion should dominate and $p$ is arbitrarily close to 1, provided Sc is larger than a certain power (depending on $p$) of the Grashof number. We also derive estimates which suggest that in 2D, for Sc${}\\sim1$ a wide tracer cascade can coexist with a significant inverse energy cascade at Grashof numbers large enough to produce a turbulent flow.

  6. Fourier analysis of multi-tracer cosmological surveys

    CERN Document Server

    Abramo, L Raul; Loureiro, Arthur

    2015-01-01

    We present optimal quadratic estimators for the Fourier analysis of cosmological surveys that detect several different types of tracers of large-scale structure. Our estimators can be used to simultaneously fit the matter power spectrum and the biases of the tracers - as well as redshift-space distortions (RSDs), non-Gaussianities (NGs), or any other effects that are manifested through differences between the clusterings of distinct species of tracers. Our estimators reduce to the one by Feldman, Kaiser & Peacock (ApJ 1994, FKP) in the case of a survey consisting of a single species of tracer. We show that the multi-tracer estimators are unbiased, and that their covariance is given by the inverse of the multi-tracer Fisher matrix (Abramo, MNRAS 2013; Abramo & Leonard, MNRAS 2013). When the biases, RSDs and NGs are fixed to their fiducial values, and one is only interested in measuring the underlying power spectrum, our estimators are projected into the estimator found by Percival, Verde & Peacock ...

  7. Quantifying solute transport processes: are chemically "conservative" tracers electrically conservative?

    Science.gov (United States)

    Singha, Kamini; Li, Li; Day-Lewis, Frederick D.; Regberg, Aaron B.

    2012-01-01

    The concept of a nonreactive or conservative tracer, commonly invoked in investigations of solute transport, requires additional study in the context of electrical geophysical monitoring. Tracers that are commonly considered conservative may undergo reactive processes, such as ion exchange, thus changing the aqueous composition of the system. As a result, the measured electrical conductivity may reflect not only solute transport but also reactive processes. We have evaluated the impacts of ion exchange reactions, rate-limited mass transfer, and surface conduction on quantifying tracer mass, mean arrival time, and temporal variance in laboratory-scale column experiments. Numerical examples showed that (1) ion exchange can lead to resistivity-estimated tracer mass, velocity, and dispersivity that may be inaccurate; (2) mass transfer leads to an overestimate in the mobile tracer mass and an underestimate in velocity when using electrical methods; and (3) surface conductance does not notably affect estimated moments when high-concentration tracers are used, although this phenomenon may be important at low concentrations or in sediments with high and/or spatially variable cation-exchange capacity. In all cases, colocated groundwater concentration measurements are of high importance for interpreting geophysical data with respect to the controlling transport processes of interest.

  8. Determination of stream reaeration coefficients by use of tracers

    Science.gov (United States)

    Kilpatrick, F.A.; Rathbun, R.E.; Yotsukura, Nobuhiro; Parker, G.W.; DeLong, L.L.

    1989-01-01

    Stream reaeration is the physical absorption of oxygen from the atmosphere by a flowing stream. This is the primary process by which a stream replenishes the oxygen consumed in the biodegradation of organic wastes. Prior to 1965, reaeration rate coefficients could be estimated only by indirect methods. In 1965, a direct method of measuring stream reaeration coefficients was developed whereby a radioactive tracer gas was injected into a stream-the principle being that the tracer gas would be desorbed from the stream inversely to how oxygen would be absorbed. The technique has since been modified by substituting hydrocarbon gases for the radioactive tracer gas. This manual describes the slug-injection and constant-rate-injection methods of measuring gas-tracer desorption. Emphasis is on the use of rhodamine WT dye as a relatively conservative tracer and propane as the nonconservative gas tracer, on planning field tests, on methods of injection, sampling, and analysis, and on techniques for computing desorption and reaeration coefficients.

  9. Thiazole-based nitrogen mustards: Design, synthesis, spectroscopic studies, DFT calculation, molecular docking, and antiproliferative activity against selected human cancer cell lines

    Science.gov (United States)

    Łączkowski, Krzysztof Z.; Świtalska, Marta; Baranowska-Łączkowska, Angelika; Plech, Tomasz; Paneth, Agata; Misiura, Konrad; Wietrzyk, Joanna; Czaplińska, Barbara; Mrozek-Wilczkiewicz, Anna; Malarz, Katarzyna; Musioł, Robert; Grela, Izabela

    2016-09-01

    Synthesis, characterization and investigation of antiproliferative activity of ten thiazole-based nitrogen mustard against human cancer cells lines (MV4-11, A549, MCF-7 and HCT116) and normal mouse fibroblast (BALB/3T3) is presented. The structures of novel compounds were determined using 1H and 13C NMR, FAB(+)-MS, and elemental analyses. Among the derivatives, 5b, 5c, 5e, 5f and 5i were found to exhibit high activity against human leukaemia MV4-11 cells with IC50 values of 2.17-4.26 μg/ml. The cytotoxic activity of compound 5c and 5f against BALB/3T3 cells is up to 20 times lower than against cancer cell lines. Our results also show that compounds 5e and 5i have very strong activity against MCF-7 and HCT116 with IC50 values of 3.02-4.13 μg/ml. Moreover, spectroscopic characterization and cellular localization for selected compound were performed. In order to identify potential drug targets we perform computer simulations with DNA-binding site of hTopoI and hTopoII and quantum chemical calculation of interaction and binding energies in complexes of the five most active compounds with guanine.

  10. Acalypha indica Linn: Biogenic synthesis of silver and gold nanoparticles and their cytotoxic effects against MDA-MB-231, human breast cancer cells

    Directory of Open Access Journals (Sweden)

    C. Krishnaraj

    2014-12-01

    Full Text Available This study reports the in vitro cytotoxic effect of biologically synthesized silver and gold nanoparticles against MDA-MB-231, human breast cancer cells. Formation of silver and gold nanoparticles was observed within 30 min and the various characterization techniques such as UV–vis spectrophotometer, FE-SEM, TEM and XRD studies were confirmed the synthesis of nanoparticles. Further, MTT, acridine orange and ethidium bromide (AO/EB dual staining, caspase-3 and DNA fragmentation assays were carried out using various concentrations of silver and gold nanoparticles ranging from 1 to 100 μg/ml. At 100 μg/ml concentration, the plant extract derived nanoparticles exhibited significant cytotoxic effects and the apoptotic features were confirmed through caspase-3 activation and DNA fragmentation assays. Thus, the results of the present study indicate that biologically synthesized silver and gold nanoparticles might be used to treat breast cancer; however, it necessitates clinical studies to ascertain their potential as anticancer agents.

  11. Synthesis and evaluation of multi-wall carbon nanotube–paclitaxel complex as an anti-cancer agent

    Science.gov (United States)

    Ghasemvand, Fariba; Biazar, Esmaeil; Tavakolifard, Sara; Khaledian, Mohammad; Rahmanzadeh, Saeid; Momenzadeh, Daruosh; Afroosheh, Roshanak; Zarkalami, Faezeh; Shabannezhad, Marjan; Hesami Tackallou, Saeed; Massoudi, Nilofar; Heidari Keshel, Saeed

    2016-01-01

    Aim: The aim of this study was to design multi-walled carbon nanotubes (MWCNTs) loaded with paclitaxel (PTX) anti-cancer drug and investigate its anti-cancerous efficacy of human gastric cancer. Background: Carbon nanotubes (CNTs) represent a novel nano-materials applied in various fields such as drug delivery due to their unique chemical properties and high drug loading. Patients and methods: In this study, multi-walled carbon nanotubes (MWCNTs) pre-functionalized covalently with a paclitaxel (PTX) as an anti-cancer drug and evaluated by different analyses including, scanning electron microscope (SEM), particle size analyzer and cellular analyses. Results: A well conjugated of anti-cancer drug on the carbon nanotube surfaces was shown. This study demonstrates that the MWCN-PTX complex is a potentially useful system for delivery of anti-cancer drugs. The flow cytometry, CFU and MTT assay results have disclosed that MWCNT/PTXs might promote apoptosis in MKN-45 gastric adenocarcinoma cell line. Conclusion: According to results, our simple method can be designed a candidate material for chemotherapy. It has presented a few bio-related applications including, their successful use as a nano-carriers for drug transport. PMID:27458512

  12. CANCER

    Directory of Open Access Journals (Sweden)

    N. Kavoussi

    1973-09-01

    Full Text Available There are many carcinogenetic elements in industry and it is for this reason that study and research concerning the effect of these materials is carried out on a national and international level. The establishment and growth of cancer are affected by different factors in two main areas:-1 The nature of the human or animal including sex, age, point and method of entry, fat metabolism, place of agglomeration of carcinogenetic material, amount of material absorbed by the body and the immunity of the body.2 The different nature of the carcinogenetic material e.g. physical, chemical quality, degree of solvency in fat and purity of impurity of the element. As the development of cancer is dependent upon so many factors, it is extremely difficult to determine whether a causative element is principle or contributory. Some materials are not carcinogenetic when they are pure but become so when they combine with other elements. All of this creates an industrial health problem in that it is almost impossible to plan an adequate prevention and safety program. The body through its system of immunity protects itself against small amounts of carcinogens but when this amount increases and reaches a certain level the body is not longer able to defend itself. ILO advises an effective protection campaign against cancer based on the Well –equipped laboratories, Well-educated personnel, the establishment of industrial hygiene within factories, the regular control of safety systems, and the implementation of industrial health principles and research programs.

  13. Oil industry first field trial of inter-well reservoir nanoagent tracers

    Science.gov (United States)

    Kanj, Mazen Y.; Kosynkin, Dmitry V.

    2015-05-01

    This short manuscript highlights the industry's first proven reservoir nanoagents' design and demonstrates a successful multi-well field trial using these agents. Our fundamental nanoparticles tracer template, A-Dots or Arab-D Dots, is intentionally geared towards the harsh but prolific Arab-D carbonate reservoir environment of 100+°C temperature, 150,000+ppm salinity, and an abundant presence of divalent ions in the connate water. Preliminary analyses confirmed nanoparticles' breakthrough at a producer nearly 500m from the injector at the reservoir level; thus, proving the tracer nanoparticles' mobility and transport capability. This is considered industry-first and a breakthrough achievement complementing earlier accomplishments in regard to the nanoagents' reservoir stability with the first successful single well test and ease of scale up with the synthesis of one metric ton of this material. The importance of this accomplishment is not in how sophisticated is the sensing functionalities of this design but rather in its stability, mobility, scalability, and field application potentials. This renders the concept of having active, reactive, and even communicative, in-situ reservoir nanoagents for underground sensing and intervention a well anticipated near-future reality.

  14. Neonatal Respiratory Diseases in the Newborn Infant: Novel Insights from Stable Isotope Tracer Studies.

    Science.gov (United States)

    Carnielli, Virgilio P; Giorgetti, Chiara; Simonato, Manuela; Vedovelli, Luca; Cogo, Paola

    2016-01-01

    Respiratory distress syndrome is a common problem in preterm infants and the etiology is multifactorial. Lung underdevelopment, lung hypoplasia, abnormal lung water metabolism, inflammation, and pulmonary surfactant deficiency or disfunction play a variable role in the pathogenesis of respiratory distress syndrome. High-quality exogenous surfactant replacement studies and studies on surfactant metabolism are available; however, the contribution of surfactant deficiency, alteration or dysfunction in selected neonatal lung conditions is not fully understood. In this article, we describe a series of studies made by applying stable isotope tracers to the study of surfactant metabolism and lung water. In a first set of studies, which we call 'endogenous studies', using stable isotope-labelled intravenous surfactant precursors, we showed the feasibility of measuring surfactant synthesis and kinetics in infants using several metabolic precursors including plasma glucose, plasma fatty acids and body water. In a second set of studies, named 'exogenous studies', using stable isotope-labelled phosphatidylcholine tracer given endotracheally, we could estimate surfactant disaturated phosphatidylcholine pool size and half-life. Very recent studies are focusing on lung water and on the endogenous biosynthesis of the surfactant-specific proteins. Information obtained from these studies in infants will help to better tailor exogenous surfactant treatment in neonatal lung diseases.

  15. Three components of cigarette smoke altered the growth and apoptosis of metastatic colon cancer cells via inducing the synthesis of reactive oxygen species and endoplasmic reticulum stress.

    Science.gov (United States)

    Lee, Hae-Miru; Kim, Cho-Won; Hwang, Kyung-A; Choi, Dal-Woong; Choi, Kyung-Chul

    2016-07-01

    Cigarette smoke (CS) is a well-known risk factor for carcinogenesis and has been found to be related to the occurrence and development of colon cancer. In this study, the effect of formaldehyde (FA), benzene (Bz), and isoprene (IP), which are included in main components of CS, on cell viability and apoptosis of SW620 colorectal cancer cells was examined to identify the connection between CS components and colon cancer. In cell viability assay, FA, Bz, and IP decreased cell viability of SW620 cells in a dose dependent manner. In Western blot assay, the protein expression of cell cycle related genes, cyclin D1 & E1, was decreased by FA, Bz, and IP, which corresponded to their inhibitory effect on cell viability. In addition, FA, Bz, and IP increased the protein expression of pro-apoptotic genes, C/EBP homologous protein (CHOP) and Bax, and reduced the protein expression of anti-apoptotic gene, Bcl-2. In reactive oxygen species (ROS) assay using dichlorofluorescin diacetate (DCFH-DA), FA, Bz, and IP increased the ROS production in SW620 cells. In the measurement of apoptotic cells, the numbers of apoptotic cells were increased by the treatment of FA, Bz, and IP. As CHOP is an endoplasmic reticulum (ER)-stress related apoptosis marker of which production is induced by ROS, it was considered that these CS components induce apoptosis of SW620 cells by increasing ROS synthesis and ER-stress. Taken together, these results showed that CS components, i.e., FA, Bz, and IP, inhibited the cell viability of SW620 cells by down-regulating the protein expression of cyclin D1 & E1 and induced apoptosis of SW620 cells by increasing ROS production and simultaneously activating ER-stress.

  16. Experiences and Preferences for End-of-Life Care for Young Adults with Cancer and Their Informal Carers: A Narrative Synthesis.

    Science.gov (United States)

    Ngwenya, Nothando; Kenten, Charlotte; Jones, Louise; Gibson, Faith; Pearce, Susie; Flatley, Mary; Hough, Rachael; Stirling, L Caroline; Taylor, Rachel M; Wong, Geoff; Whelan, Jeremy

    2017-01-11

    To review the qualitative literature on experiences of and preferences for end-of-life care of people with cancer aged 16-40 years (young adults) and their informal carers. A systematic review using narrative synthesis of qualitative studies using the 2006 UK Economic and Social Research Council research methods program guidance. Seven electronic bibliographic databases, two clinical trials databases, and three relevant theses databases were searched from January 2004 to October 2015. Eighteen articles were included from twelve countries. The selected studies included at least 5% of their patient sample within the age range 16-40 years. The studies were heterogeneous in their aims, focus, and sample, but described different aspects of end-of-life care for people with cancer. Positive experiences included facilitating adaptive coping and receiving palliative home care, while negative experiences were loss of "self" and nonfacilitative services and environment. Preferences included a family-centered approach to care, honest conversations about end of life, and facilitating normality. There is little evidence focused on the end-of-life needs of young adults. Analysis of reports including some young adults does not explore experience or preferences by age; therefore, it is difficult to identify age-specific issues clearly. From this review, we suggest that supportive interventions and education are needed to facilitate open and honest communication at an appropriate level with young people. Future research should focus on age-specific evidence about the end-of-life experiences and preferences for young adults with cancer and their informal carers.

  17. Tetra- and mono-organotin reagents in palladium-mediated cross-coupling reactions for the labeling with carbon-11 of PET tracers

    Energy Technology Data Exchange (ETDEWEB)

    Bourdier, T.; Huiban, M.; Sobrio, F.; Perrio, C.; Barre, E. [Groupe de Dev Methodol en Tomographie par Emission de Positons, UMR CEA 2E, Universite deCaen, Centre Cyceron, F-14070 Caen Cedex (France); Fouquet, A.; Huet, A. [Laboratoire de Chimie Organique et Organometallique, UMR CNRS 3802, Univ Bordeaux I, F-33405 Talence Cedex (France)

    2008-07-01

    The palladium-catalyzed cross-coupling reactions between a (trimethylstannyl)arene and [{sup 11}C]methyl iodide (Stille reaction) or between an aryl halide and a [{sup 11}C]monomethyltin reagent issued from Lappert's stannylene, were developed for the synthesis of polyfunctional [{sup 11}C]methyl quinolines and quinoline-imides as potential tracers for positron emission tomography (PET). (authors)

  18. Synthesis of Colloidal Quantum Dots Coated with Mercaptosuccinic Acid for Early Detection and Therapeutics of Oral Cancers

    Science.gov (United States)

    Jocelin, G.; Arivarasan, A.; Ganesan, M.; Prasad, N. Rajendra; Sasikala, G.

    2016-04-01

    Quantum dots (QDs) are gaining widespread recognition for its luminescence behavior and unique photo physical properties as a bio-marker and inorganic fluorophore. In spite of such rampant advantages, its application is clinically hampered depending on the surface coating decreasing its luminescence efficiency. The present study reports preparation of CdTe QDs capped with biologically active thiol based material, mercaptosuccinic acid (MSA) for diagnosis of oral cancer (KB) cells by acting as a fluorophore marking targeted tumor cells and at the same time exhibiting certain cytotoxic effects. Synthesized MSA coated CdTe QDs is spherical in shape with an average particle size of 3-5nm. In vitro, the rapid uptake of MSA CdTe QDs in oral cancer cell lines were assessed through fluorescence microscopy. Further, this study evaluates the therapeutic efficiency of MSA CdTe QDs in human oral cancer cell lines using MTT analysis. MSA CdTe QDs exhibit significant cytotoxicity in oral cancer cells in a dose dependent manner with low IC50 when compared with other raw CdTe QDs. MSA CdTe QDs were also treated with human lymphocytes (normal cells) to assess and compare the toxicity profile of QDs in normal and oral tumors. The results of our present study strengthen our hypothesis of using MSA CdTe QDs as detector for tracking and fluorescence imaging of oral cancer cells and exhibiting sufficient cytotoxicity in them.

  19. Copper Ion as a New Leakage Tracer

    Directory of Open Access Journals (Sweden)

    Modaresi J.

    2013-12-01

    Full Text Available Statement of Problem: Most failures of root canal treatments are caused by bacteria. Studies showed that the most common cause of endodontic failures were the incomplete obturation of the root canal and the lack of adequate apical seal. Some in-vitro methods are used to estimate sealing quality, generally by measuring microleakage that allows the tracer agent to penetrate the filled canal.Purpose: Conventional methods of evaluating the seal of endodontically treated teeth are complicated and have some drawbacks. We used copper ion diffusion method to assess the leakage and the results were compared to dye penetration method.Materials and Method: The crowns of 21 extracted teeth were cut off at the CEJ level. After preparing the canals, the teeth were placed in tubes containing saline. They were divided randomly into 15 experimental cases; 3 positive and 3 negative controls. Positive controls were filled by single cone without sealer while the experimental and the negative control groups were filled by lateral technique. The coronal portion of gutta was removed and 9mm was left. The external surface of each tooth was coated with nail polish. Two millimeters of apical portion was immersed into 9ml of distilled water and 0.3ml of CuSO4 solution was injected into the coronal portion. After 2 days, copper sulfate was measured by an atomic absorption spectrophotometer. The teeth were then immersed in 2% methylene blue for 24 hours, sectioned and the extent of dye penetration was measured by a stereomicroscope.Results: The maximum and minimum recorded copper ion concentrations for the experimental group were 18.37 and 2.87ppm respectively. The maximum and minimum recorded dye penetrations for the experimental group were 8.5 and 3.5mm respectively. The statistical analysis, adopting paired samples test, showed poor correlation between average recorded results of two methods.Conclusion: Based on our results, there was no significant correlation between

  20. Assessing preferential flow by simultaneously injecting nanoparticle and chemical tracers

    KAUST Repository

    Subramanian, S. K.

    2013-01-01

    The exact manner in which preferential (e.g., much faster than average) flow occurs in the subsurface through small fractures or permeable connected pathways of other kinds is important to many processes but is difficult to determine, because most chemical tracers diffuse quickly enough from small flow channels that they appear to move more uniformly through the rock than they actually do. We show how preferential flow can be assessed by injecting 2 to 5 nm carbon particles (C-Dots) and an inert KBr chemical tracer at different flow rates into a permeable core channel that is surrounded by a less permeable matrix in laboratory apparatus of three different designs. When the KBr tracer has a long enough transit through the system to diffuse into the matrix, but the C-Dot tracer does not, the C-Dot tracer arrives first and the KBr tracer later, and the separation measures the degree of preferential flow. Tracer sequestration in the matrix can be estimated with a Peclet number, and this is useful for experiment design. A model is used to determine the best fitting core and matrix dispersion parameters and refine estimates of the core and matrix porosities. Almost the same parameter values explain all experiments. The methods demonstrated in the laboratory can be applied to field tests. If nanoparticles can be designed that do not stick while flowing through the subsurface, the methods presented here could be used to determine the degree of fracture control in natural environments, and this capability would have very wide ranging value and applicability.

  1. Multiple Tracer Tests in Porous Media During Clogging

    Science.gov (United States)

    Englert, A.; Banning, A.; Siegmund, J.; Freye, S.; Goekpinar, T.

    2015-12-01

    Transport processes are known to be governed by the physical and chemical heterogeneity of the subsurface. Clogging processes can alter this heterogeneity as function of time and thus can modify transport. To understand transport under clogging conditions and to unravel the potential of multiple tracer tests to characterize such transport process we perform column and sandbox experiments. Our recently developed column and sandbox experiments are used to perform multiple tracer tests during clogging. In a first set of experiments, a cubic cell of 0.1 m x 0.1 m x 0.1 m is used to experimentally estimate flow and transport characteristics of an unconsolidated sediment through Darcy and tracer experiments. The water streaming through the experiment is amended with ammonium sulfate permanently. Salt tracers are added to the streaming water repeatedly, to be detected at micro electrodes at the inflow and the outflow of the cubic cell. Through repeated syringe injections of a barium chloride solution into the center of the cubic cell clogging processes are forced to occur around the mixing zone of the injected and streaming water by precipitation of barium sulfate. In a second set of experiments, a sandbox model including a sediment body of 0.3 m x 0.3 m x 0.1 m is used. Tracer, streaming, and injection water chemistry is kept similar to the cubic cell experiments. However, tracer breakthrough is now detected at nine positions within the experiment and at the inflow and the outflow of the sandbox model. Injection of barium chloride solution is now at two locations around the center of the sandbox model. Flow and transport characteristics of the sediment body are estimated based on Darcy and tracer experiments, which are performed repeatedly. Combined analysis of local and ensemble breakthrough curves and integrated numerical modeling will be used to understand effective and local flow and transport in a in a porous medium during clogging.

  2. Testing fundamentals: The chemical state of geochemical tracers in biominerals.

    Science.gov (United States)

    Branson, O.; Redfern, S. A. T.; Read, E.; Elderfield, H.

    2015-12-01

    The use of many carbonate-derived geochemical proxies is underpinned by the assumption that tracer elements are incorporated 'ideally' as impurities the mineral lattice, following relatively straightforward kinetic and thermodynamic drives. This allows comparison to inorganic precipitation experiments, and provides a systematic starting point from which to translate geochemical tracers to environmental records. Biomineral carbonates are a prominent source of geochemical proxy material, and are far from an ideal inorganic system. They are structurally and compositionally heterogeneous mineral-organic composites, produced in tightly controlled biological environments, possibly via non-classical crystal growth mechanisms. Biominerals offer numerous opportunities for tracers to be incorporated in a 'non-ideal' state. For instance, tracers could be hosted within the organic component of the structure, in interstitial micro-domains of a separate mineral phase, or in localized high-impurity clusters. If a proxy element is hosted in a non-ideal state, our understanding of its incorporation and preservation is flawed, and the theoretical basis behind the proxies derived from it must be reevaluated. Thus far, the assumption of ideal tracer incorporation has remained largely untested, owing to the spatial resolution and sensitivity limits of available techniques. Developments in high-resolution, high-sensitivity X-ray spectroscopy at Scanning Transmission X-Ray Microscopes (STXMs) have allowed us to measure trace element coordination in foraminiferal calcite, at length-scales relevant to biomineralisation processes and tracer incorporation. This instrument has allowed us to test the fundamental assumptions behind several geochemical proxy elements. We present a summary of four STXM studies, assessing the chemical state and distribution of Mg (Branson et al, 2014), B (Branson et al, 2015), S and Na (unpub.), and highlight the implications of these data for the use of these

  3. One-pot synthesis of FePt/CNTs nanocomposites for efficient cellular imaging and cancer therapy

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Weihong; Zheng, Xiuwen, E-mail: xwzheng1976@163.com [Linyi University, School of Chemistry & Chemical Engineering, Shandong Provincial Key Laboratory of Detection Technology for Tumor Makers (China); Li, Shulian [Linyi Tumor Hospital (China); Zhang, Wei; Wen, Xin [Linyi University, School of Chemistry & Chemical Engineering, Shandong Provincial Key Laboratory of Detection Technology for Tumor Makers (China); Yue, Ludan [Shandong Normal University (China); Wang, Jinlong [Shandong University of Technology (China)

    2015-11-15

    Here, we developed a facile route to synthesize carbon nanotube-based FePt nanocomposites (FePt/CNTs) as a potential theranostic platform in the cancer treatment. FePt/CNTs were firstly synthesized via one-pot polyol route, and then functionalized with 6-arm-polyethylene glycol-amine polymer. The average size of FePt nanoparticles (NPs) is 3–4 nm, which is dispersed on the CNT surface (ca.50–150 nm). The as-prepared FePt NPs display high cytotoxicity by highly reactive oxygen species in cancer cells. Folic acid and fluorescein isothiocyanate are assembled onto the surface of FePt/CNTs for effective targeting of folate receptor-positive cancer cells and simultaneously for the visualization of cellular uptake. Therefore, the FePt/CNTs NPs capability of simultaneously performing diagnosis, therapy, and targeting is, therefore, promising for future potential widespread application in biomedicine.

  4. Design, Synthesis and Biological Evaluation of Novel Rapamycin Benzothiazole Hybrids as mTOR Targeted Anti-cancer Agents.

    Science.gov (United States)

    Xie, Lijun; Huang, Jie; Chen, Xiaoming; Yu, Hui; Li, Kualiang; Yang, Dan; Chen, Xiaqin; Ying, Jiayin; Pan, Fusheng; Lv, Youbing; Cheng, Yuanrong

    2016-01-01

    The immunosuppressant drug rapamycin, was firstly identified as a mammalian target of rapamycin (mTOR) allosteric inhibitor, and its derivatives have been successfully developed as anti-cancer drugs. Therefore, finding rapamycin derivatives with better anti-cancer activity has been proved to be an effective way to discover new targeted anti-cancer drugs. In this paper, structure modification was performed at the C-43 position of rapamycin using bioisosterism and a hybrid approach: a series of novel rapamycin-benzothiazole hybrids 4a-e, 5a-c, and 9a, b have been designed, synthesized and evaluated for their anti-cancer activity against Caski, CNE-2, SGC-7901, PC-3, SK-NEP-1 and A-375 human cancer cell lines. Some of these compounds (4a-e, 9a, b) displayed good to excellent potency against the Caski and SK-NEP-1 cell line as compared with rapamycin. Compound 9b as the most active compound showed IC50 values of 8.3 (Caski) and 9.6 μM (SK-NEP-1), respectively. In addition, research on the mechanism showed that 9b was able to cause G1 phase arrest and induce apoptosis in the Caski cell line. Most importantly, it significantly decreased the phosphorylation of S6 ribosomal protein, p70S6K1 and 4EBP1, which indicated that 9b inhibited the cancer cell growth by blocking the mTOR pathway and may have the potential to become a new mTOR inhibitor.

  5. CdO-NPs; synthesis from 1D new nano Cd coordination polymer, characterization and application as anti-cancer drug for reducing the viability of cancer cells

    Science.gov (United States)

    Afzalian Mend, Behnaz; Delavar, Mahmoud; Darroudi, Majid

    2017-04-01

    The hexagonal CdO nano-particles (CdO-NPs) was prepared using new nano Cd coordination polymer, [Cd(NO3)(bipy)(pzca)]n (1) as a precursor, through direct calcination process at 500 °C. The precursor (1) was synthesized by sonochemical method. The new nano compound (1) was characterized by IR spectroscopy, elemental analyses, X-ray powder diffraction (XRD), transmission electron microscopy (TEM) and thermal gravimetric analyses. The structure of nano coordination polymer was determined by comparing the XRD pattern of nano and single-crystal of compound (1). The nano CdO was characterized by scanning electron microscopy (SEM) and X-ray powder diffraction (XRD). In addition, the activity and efficiency of nano CdO as an anti-cancer drug was studied on cancer cells with different concentration. The results shows that the viability of cancer cells reduced above 2 μg/mL of CdO-NPs concentration.

  6. Comparison of protein- and polysaccharide-based nanoparticles for cancer therapy: synthesis, characterization, drug release, and interaction with a breast cancer cell line.

    Science.gov (United States)

    Akbal, Öznur; Erdal, Ebru; Vural, Tayfun; Kavaz, Doğa; Denkbaş, Emir Baki

    2017-03-01

    In this study, human serum albumin (HSA) was used as a protein-based material and poly (3-hydroxybutyrate) (PHB)-carboxymethyl chitosan (CMCh) as a polysaccharide-based material for the production of nanoparticles to be used as nanocarriers in cancer therapy. HSA and PHB-CMCh nanoparticles were prepared and characterized with a Zeta Sizer, Fourier transform infrared spectroscopy, scanning electron microscopy, and atomic force microscope. The effects of the pH value of the suspending medium and the amounts of crosslinker and polymer concentration on nanoparticle size and size distribution were investigated. The anticancer-agent etoposide was used as a model drug and encapsulated in nanoparticles to obtain drug release profiles. The entrapment efficiency of HSA nanoparticles was found to be greater than that of PHB-CMCh nanoparticles. To achieve "active" targeting of cancer cells, the nanoparticles were modified with concanavalin A. In the final step of the study, the interaction of nanoparticles with cancer cells was investigated in cytotoxicity and cellular uptake studies.

  7. Pre-clinical evaluation of a novel CEA-targeting near-infrared fluorescent tracer delineating colorectal and pancreatic tumors

    Science.gov (United States)

    Boonstra, Martin C.; Tolner, Berend; Schaafsma, Boudewijn E.; Boogerd, Leonora S.F.; Prevoo, Hendrica A.J.M; Bhavsar, Guarav; Kuppen, Peter J.K.; Sier, Cornelis F.M.; Bonsing, Bert A.; Frangioni, John V.; van de Velde, Cornelis J.H.; Chester, Kerry A.; Vahrmeijer, Alexander L.

    2016-01-01

    Surgery is the cornerstone of oncologic therapy with curative intent. However, identification of tumor cells in the resection margins is difficult, resulting in non-radical resections, increased cancer recurrence and subsequent decreased patient survival. Novel imaging techniques that aid in demarcating tumor margins during surgery are needed. Overexpression of carcinoembryonic antigen (CEA) is found in the majority of gastro-intestinal carcinomas, including colorectal and pancreas. We developed ssSM3E/800CW, a novel CEA-targeted near-infrared fluorescent (NIRF) tracer, based on a disulphide stabilized single-chain antibody fragment (ssScFv), to visualize colorectal and pancreatic tumors in a clinically translatable setting. The applicability of the tracer was tested for cell and tissue binding characteristics and dosing using immunohistochemistry, flow cytometry, cell-based plate assays and orthotopic colorectal (HT-29, well differentiated) and pancreatic (BXPC-3, poorly differentiated) xenogeneic human-mouse models. NIRF signals were visualized using the clinically compatible FLARE™ imaging system. Calculated clinically relevant doses of ssSM3E/800CW selectively accumulated in colorectal and pancreatic tumors/cells, with highest tumor-to-background ratios of 5.1±0.6 at 72 h post-injection, which proved suitable for intra-operative detection and delineation of tumor boarders and small (residual) tumor-nodules in mice, between 8 h and 96 h post-injection. Ex vivo fluorescence imaging and pathologic examination confirmed tumor-specificity and the distribution of the tracer. Our results indicate that ssSM3E/800CW shows promise as a diagnostic tool to recognize colorectal and pancreatic cancers for fluorescent-guided surgery applications. If successful translated clinically, this tracer could help improve the completeness of surgery and thus survival. PMID:25895046

  8. TracerLPM (Version 1): An Excel® workbook for interpreting groundwater age distributions from environmental tracer data

    Science.gov (United States)

    Jurgens, Bryant C.; Böhlke, J.K.; Eberts, Sandra M.

    2012-01-01

    TracerLPM is an interactive Excel® (2007 or later) workbook program for evaluating groundwater age distributions from environmental tracer data by using lumped parameter models (LPMs). Lumped parameter models are mathematical models of transport based on simplified aquifer geometry and flow configurations that account for effects of hydrodynamic dispersion or mixing within the aquifer, well bore, or discharge area. Five primary LPMs are included in the workbook: piston-flow model (PFM), exponential mixing model (EMM), exponential piston-flow model (EPM), partial exponential model (PEM), and dispersion model (DM). Binary mixing models (BMM) can be created by combining primary LPMs in various combinations. Travel time through the unsaturated zone can be included as an additional parameter. TracerLPM also allows users to enter age distributions determined from other methods, such as particle tracking results from numerical groundwater-flow models or from other LPMs not included in this program. Tracers of both young groundwater (anthropogenic atmospheric gases and isotopic substances indicating post-1940s recharge) and much older groundwater (carbon-14 and helium-4) can be interpreted simultaneously so that estimates of the groundwater age distribution for samples with a wide range of ages can be constrained. TracerLPM is organized to permit a comprehensive interpretive approach consisting of hydrogeologic conceptualization, visual examination of data and models, and best-fit parameter estimation. Groundwater age distributions can be evaluated by comparing measured and modeled tracer concentrations in two ways: (1) multiple tracers analyzed simultaneously can be evaluated against each other for concordance with modeled concentrations (tracer-tracer application) or (2) tracer time-series data can be evaluated for concordance with modeled trends (tracer-time application). Groundwater-age estimates can also be obtained for samples with a single tracer measurement at one

  9. Development of radioisotope tracer technology and nucleonic control system

    Energy Technology Data Exchange (ETDEWEB)

    Jin, Joon Ha; Lee, Myun Joo; Jung, Sung Hee and others

    1999-04-01

    The purpose of this study is to develop the radioisotope tracer technology, which can be used in solving industrial and environmental problems and basic technology of nuclear control systems that are widely used for automation of industrial plants, and to build a strong tracer group to support the local industries. In relation to the tracer technology, the data acquisition system, the column scanning equipment and the detection pig for a leakage test have been developed. In order to use in analyzing data of tracer experiments, a computer program for the analysis of residence time distribution has been created as well. These results were utilized in developing the tracer technologies, such as the column scanning, the flow measurement using the dilution method, the simultaneous monitoring rotational movement of piston rings and the optimization of a waste water treatment facility, and the technologies were successfully demonstrated in the local industrial. The stripper of RFCC reactor has been examined to find an unwanted structure in it by imminent request from the industry. Related to the development of nucleonic control system, the state of art report on the technology has been written and an equipment for the analysis of asphalt content has been developed. (author)

  10. Passive Tracer Dynamics in 4 Point-Vortex Flow

    CERN Document Server

    Laforgia, A; Kuznetsov, L V; Zaslavsky, G M

    2000-01-01

    The advection of passive tracers in a system of 4 identical point vortices is studied when the motion of the vortices is chaotic. The phenomenon of vortex-pairing has been observed and statistics of the pairing time is computed. The distribution exhibits a power-law tail with exponent (\\sim 3.6), implying finite average pairing time. Tracer motion is studied for a chosen initial condition of the vortex system. Accessible phase space is investigated. The size of the cores around the vortices is well approximated by the minimum inter-vortex distance and stickiness to these cores is observed. We investigate the origin of stickiness which we link to the phenomenon of vortex pairing and jumps of tracers between cores. Motion within the core is considered and fluctuations are shown to scale with tracer-vortex distance (r) as (r^{6}). No outward or inward diffusion of tracers are observed. This investigation allows the separation of the accessible phase space in four distinct regions, each with its own specific prop...

  11. Natural organic compounds as tracers for biomass combustion in aerosols

    Energy Technology Data Exchange (ETDEWEB)

    Simoneit, B.R.T. [Brookhaven National Lab., Upton, NY (United States)]|[Oregon State Univ., Corvallis, OR (United States). Coll. of Oceanic and Atmospheric Sciences; Abas, M.R. bin [Brookhaven National Lab., Upton, NY (United States)]|[Univ. of Malaya, Kuala Lumpur (Malaysia); Cass, G.R. [Brookhaven National Lab., Upton, NY (United States)]|[California Inst. of Tech., Pasadena, CA (United States). Environmental Engineering Science Dept.; Rogge, W.F. [Brookhaven National Lab., Upton, NY (United States)]|[Florida International Univ., University Park, FL (United States). Dept. of Civil and Environmental Engineering; Mazurek, M.A. [Brookhaven National Lab., Upton, NY (United States); Standley, L.J. [Academy of Natural Sciences, Avondale, PA (United States). Stroud Water Research Center; Hildemann, L.M. [Stanford Univ., CA (United States). Dept. of Civil Engineering

    1995-08-01

    Biomass combustion is an important primary source of carbonaceous particles in the global atmosphere. Although various molecular markers have already been proposed for this process, additional specific organic tracers need to be characterized. The injection of natural product organic tracers to smoke occurs primarily by direct volatilization/steam stripping and by thermal alteration based on combustion temperature. The degree of alteration increases as the burn temperature rises and the moisture content of the fuel decreases. Although the molecular composition of organic matter in smoke particles is highly variable, the molecular structures of the tracers are generally source specific. The homologous compound series and biomarkers present in smoke particles are derived directly from plant wax, gum and resin by volatilization and secondarily from pyrolysis of biopolymers, wax, gum and resin. The complexity of the organic components of smoke aerosol is illustrated with examples from controlled burns of temperate and tropical biomass fuels. Burning of biomass from temperate regions (i.e., conifers) yields characteristic tracers from diterpenoids as well as phenolics and other oxygenated species, which are recognizable in urban airsheds. The major organic components of smoke particles from tropical biomass are straight-chain, aliphatic and oxygenated compounds and triterpenoids. The precursor-to-product approach of organic geochemistry can be applied successfully to provide tracers for studying smoke plume chemistry and dispersion.

  12. Role of Protein Synthesis Initiation Factors in Dietary Soy Isoflavone-Mediated Effects on Breast Cancer Progression

    Science.gov (United States)

    2014-08-01

    phytochemicals in cancer prevention: mechanism of action, J Nutr., 134: 3479S-3485S, 2004. 2 Aggarwal,B.B. and Shishodia,S. Molecular targets of dietary...Neoplasia., 13: 504-515, 2011. 57 Yochum,G.S., Cleland,R. and Goodman,R.H. A genome-wide screen for beta-catenin binding sites identifies a

  13. Green synthesis of silver nanoparticles using Pimpinella anisum seeds: antimicrobial activity and cytotoxicity on human neonatal skin stromal cells and colon cancer cells

    Directory of Open Access Journals (Sweden)

    AlSalhi MS

    2016-09-01

    Full Text Available Mohamad S AlSalhi,1,2 Sandhanasamy Devanesan,1,2 Akram A Alfuraydi,3 Radhakrishnan Vishnubalaji,4 Murugan A Munusamy,3 Kadarkarai Murugan,5 Marcello Nicoletti,6 Giovanni Benelli7 1Research Chair in Laser Diagnosis of Cancers, 2Department of Physics and Astronomy, 3Department of Botany and Microbiology, College of Science, 4Stem Cell Unit, Department of Anatomy, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia; 5Division of Entomology, Department of Zoology, School of Life Sciences, Bharathiar University, Coimbatore, India; 6Department of Environmental Biology, Sapienza University of Rome, Rome, 7Department of Agriculture, Food and Environment, University of Pisa, Pisa, Italy Background: The present study focused on a simple and eco-friendly method for the synthesis of silver nanoparticles (AgNPs with multipurpose anticancer and antimicrobial activities. Materials and methods: We studied a green synthesis route to produce AgNPs by using an aqueous extract of Pimpinella anisum seeds (3 mM. Their antimicrobial activity and cytotoxicity on human neonatal skin stromal cells (hSSCs and colon cancer cells (HT115 were assessed. Results: A biophysical characterization of the synthesized AgNPs was realized: the morphology of AgNPs was determined by transmission electron microscopy, energy dispersive spectroscopy, X-ray powder diffraction, and ultraviolet-vis absorption spectroscopy. Transmission electron microscopy showed spherical shapes of AgNPs of P. anisum seed extracts with a 3.2 nm minimum diameter and average diameter ranging from 3.2 to 16 nm. X-ray powder diffraction highlighted the crystalline nature of the nanoparticles, ultraviolet-vis absorption spectroscopy was used to monitor their synthesis, and Fourier transform infrared spectroscopy showed the main reducing groups from the seed extract. Energy dispersive spectroscopy was used to confirm the presence of elemental silver. We evaluated the antimicrobial potential

  14. Synthesis, characterization and in vitro evaluation of exquisite targeting SPIONs-PEG-HER in HER2+ human breast cancer cells

    Science.gov (United States)

    Hamzehalipour Almaki, Javad; Nasiri, Rozita; Idris, Ani; Majid, Fadzilah Adibah Abdul; Salouti, Mojtaba; Wong, Tet Soon; Dabagh, Shadab; Marvibaigi, Mohsen; Amini, Neda

    2016-03-01

    A stable, biocompatible and exquisite SPIONs-PEG-HER targeting complex was developed. Initially synthesized superparamagnetic iron oxide nanoparticles (SPIONs) were silanized using 3-aminopropyltrimethoxysilane (APS) as the coupling agent in order to allow the covalent bonding of polyethylene glycol (PEG) to the SPIONs to improve the biocompatibility of the SPIONs. SPIONs-PEG were then conjugated with herceptin (HER) to permit the SPIONs-PEG-HER to target the specific receptors expressed over the surface of the HER2+ metastatic breast cancer cells. Each preparation step was physico-chemically analyzed and characterized by a number of analytical methods including AAS, FTIR spectroscopy, XRD, FESEM, TEM, DLS and VSM. The biocompatibility of SPIONs-PEG-HER was evaluated in vitro on HSF-1184 (human skin fibroblast cells), SK-BR-3 (human breast cancer cells, HER+), MDA-MB-231 (human breast cancer cells, HER-) and MDA-MB-468 (human breast cancer cells, HER-) cell lines by performing MTT and trypan blue assays. The hemolysis analysis results of the SPIONs-PEG-HER and SPIONs-PEG did not indicate any sign of lysis while in contact with erythrocytes. Additionally, there were no morphological changes seen in RBCs after incubation with SPIONs-PEG-HER and SPIONs-PEG under a light microscope. The qualitative and quantitative in vitro targeting studies confirmed the high level of SPION-PEG-HER binding to SK-BR-3 (HER2+ metastatic breast cancer cells). Thus, the results reflected that the SPIONs-PEG-HER can be chosen as a favorable biomaterial for biomedical applications, chiefly magnetic hyperthermia, in the future.

  15. Study on Radioecology and Tracer of Iodine-129

    Energy Technology Data Exchange (ETDEWEB)

    Xiaolin, Hou [Riso National Laboratory, NUK, DK, Roskilde (Denmark)

    2004-07-01

    other places. (2) Reconstruction of radiation dose from I-131 in the Chernobyl contaminated regions. The investigations show a strong dependence of childhood thyroid cancer incidence on thyroid exposure dose from short-lived radioiodine isotopes (i.e. {sup 131}I, {sup 133}I) released from the Chernobyl accident. However, the short half-life of {sup 133}I (20.8 h) and {sup 131}I (8.02 d) makes the evaluation of thyroid dose from these isotopes not easy. Due to the long half-life of {sup 129}I, the {sup 129}I concentration in environmental samples can be used to reconstruct the {sup 131}I and {sup 133}I dose to thyroids. Soil samples from areas in Belarus, Russia and Sweden contaminated by the Chernobyl accident were analysed for {sup 129}I and {sup 137}Cs by gamma-spectrometry. The atomic ratios of {sup 129}I/{sup 137}Cs ranged from 0.10 to 0.30, with an average of 0.18. It confirmed that the {sup 129}I/{sup 137}Cs ratios could be to reconstruct the deposition pattern of {sup 131}I in these areas. (3) Application of I-129 as an oceanographic tracer. By analysing the time series seaweed samples collected from the coast of Denmark, Norway, and west Greenland, seawater samples from Baltic Sea, North Sea, Belt Sea, lake water from Denmark and other Baltic Seas for {sup 129}I and {sup 127}I, the transportation, mixing and water mass from North Sea to North Atlantic, Arctic and Baltic Sea and the origination of I-129 in the Baltic Sea were studied. (4) Chemical speciation of I-129. Seawater samples from in the North Sea, Kattegat and Baltic Sea were analyzed for {sup 129}I and {sup 127}I in both iodide and iodate species and total inorganic iodine. The possibility of using this method to study the geochemical cycle of iodine in the ocean was investigated. (author)

  16. Theoretical model of intravascular paramagnetic tracers effect on tissue relaxation

    DEFF Research Database (Denmark)

    Kjølby, Birgitte Fuglsang; Østergaard, Leif; Kiselev, Valerij G

    2006-01-01

    that the relaxivity of intravascular contrast agents depends significantly on the host tissue. This agrees with experimental data by Johnson et al. (Magn Reson Med 2000;44:909). In particular, the present results suggest a several-fold increase in the relaxivity of Gd-based contrast agents in brain tissue compared...... with bulk blood. The enhancement of relaxation in tissue is due to the contrast in magnetic susceptibility between blood vessels and parenchyma induced by the presence of paramagnetic tracer. Beyond the perfusion measurements, the results can be applied to quantitation of functional MRI and to vessel size......The concentration of MRI tracers cannot be measured directly by MRI and is commonly evaluated indirectly using their relaxation effect. This study develops a comprehensive theoretical model to describe the transverse relaxation in perfused tissue caused by intravascular tracers. The model takes...

  17. Preparation of intravenous cholesterol tracer using current good manufacturing practices.

    Science.gov (United States)

    Lin, Xiaobo; Ma, Lina; Racette, Susan B; Swaney, William P; Ostlund, Richard E

    2015-12-01

    Studies of human reverse cholesterol transport require intravenous infusion of cholesterol tracers. Because insoluble lipids may pose risk and because it is desirable to have consistent doses of defined composition available over many months, we investigated the manufacture of cholesterol tracer under current good manufacturing practice (CGMP) conditions appropriate for phase 1 investigation. Cholesterol tracer was prepared by sterile admixture of unlabeled cholesterol or cholesterol-d7 in ethanol with 20% Intralipid(®). The resulting material was filtered through a 1.2 micron particulate filter, stored at 4°C, and tested at time 0, 1.5, 3, 6, and 9 months for sterility, pyrogenicity, autoxidation, and particle size and aggregation. The limiting factor for stability was a rise in thiobarbituric acid-reacting substances of 9.6-fold over 9 months (P postproduction. CGMP manufacturing methods can be achieved in the academic setting and need to be considered for critical components of future metabolic studies.

  18. Comparison of /sup 13/C nuclear magnetic resonance and /sup 14/C tracer studies of hepatic metabolism. [Rats and mice

    Energy Technology Data Exchange (ETDEWEB)

    Cohen, S.M. (Merck Inst. for Therapeutic Research, Rathway, NJ); Rognstad, R.; Shulman, R.G.; Katz, J.

    1981-04-10

    The gluconeogenic pathway from /sup 13/C-labeled substrates, each of which contained the /sup 14/C-labeled counterpart at a tracer level, has been followed in isolated rat liver cells and in isolated perfused mouse liver. The gluconeogenic flux from glycerol, the synthesis of glycogen, the synthesis of glycogen, the stimulation of glycogenolysis by glucagon, the recycling of triacylglycerol, and an increase in pentose cycle activity under the influence of phenazine methosulfate were all observed directly in the /sup 13/C NMR spectra of perfused liver or isolated hepatocytes. The relative concentrations of /sup 13/C label at specific carbons measured by the NMR spectra under these conditions agreed closely with /sup 14/C isotopic distributions measured in extracts of the same doubly labeled samples for specific activities of greater than or equal to 3%. The label distributions measured by both methods were the same to within the experimental errors, which ranged from +-2% to +-7% in these experiments.

  19. Dynamics and mechanics of bed-load tracer particles

    Directory of Open Access Journals (Sweden)

    C. B. Phillips

    2014-12-01

    Full Text Available Understanding the mechanics of bed load at the flood scale is necessary to link hydrology to landscape evolution. Here we report on observations of the transport of coarse sediment tracer particles in a cobble-bedded alluvial river and a step-pool bedrock tributary, at the individual flood and multi-annual timescales. Tracer particle data for each survey are composed of measured displacement lengths for individual particles, and the number of tagged particles mobilized. For single floods we find that measured tracer particle displacement lengths are exponentially distributed; the number of mobile particles increases linearly with peak flood Shields stress, indicating partial bed load transport for all observed floods; and modal displacement distances scale linearly with excess shear velocity. These findings provide quantitative field support for a recently proposed modeling framework based on momentum conservation at the grain scale. Tracer displacement is weakly negatively correlated with particle size at the individual flood scale; however cumulative travel distance begins to show a stronger inverse relation to grain size when measured over many transport events. The observed spatial sorting of tracers approaches that of the river bed, and is consistent with size-selective deposition models and laboratory experiments. Tracer displacement data for the bedrock and alluvial channels collapse onto a single curve – despite more than an order of magnitude difference in channel slope – when variations of critical Shields stress and flow resistance between the two are accounted for. Results show how bed load dynamics may be predicted from a record of river stage, providing a direct link between climate and sediment transport.

  20. How well do different tracers constrain the firn diffusivity profile?

    Directory of Open Access Journals (Sweden)

    C. M. Trudinger

    2013-02-01

    Full Text Available Firn air transport models are used to interpret measurements of the composition of air in firn and bubbles trapped in ice in order to reconstruct past atmospheric composition. The diffusivity profile in the firn is usually calibrated by comparing modelled and measured concentrations for tracers with known atmospheric history. However, in most cases this is an under-determined inverse problem, often with multiple solutions giving an adequate fit to the data (this is known as equifinality. Here we describe a method to estimate the firn diffusivity profile that allows multiple solutions to be identified, in order to quantify the uncertainty in diffusivity due to equifinality. We then look at how well different combinations of tracers constrain the firn diffusivity profile. Tracers with rapid atmospheric variations like CH3CCl3, HFCs and 14CO2 are most useful for constraining molecular diffusivity, while &delta:15N2 is useful for constraining parameters related to convective mixing near the surface. When errors in the observations are small and Gaussian, three carefully selected tracers are able to constrain the molecular diffusivity profile well with minimal equifinality. However, with realistic data errors or additional processes to constrain, there is benefit to including as many tracers as possible to reduce the uncertainties. We calculate CO2 age distributions and their spectral widths with uncertainties for five firn sites (NEEM, DE08-2, DSSW20K, South Pole 1995 and South Pole 2001 with quite different characteristics and tracers available for calibration. We recommend moving away from the use of a firn model with one calibrated parameter set to infer atmospheric histories, and instead suggest using multiple parameter sets, preferably with multiple representations of uncertain processes, to assist in quantification of the uncertainties.

  1. How well do different tracers constrain the firn diffusivity profile?

    Directory of Open Access Journals (Sweden)

    C. M. Trudinger

    2012-07-01

    Full Text Available Firn air transport models are used to interpret measurements of the composition of air in firn and bubbles trapped in ice in order to reconstruct past atmospheric composition. The diffusivity profile in the firn is usually calibrated by comparing modelled and measured concentrations for tracers with known atmospheric history. However, in some cases this is an under-determined inverse problem, often with multiple solutions giving an adequate fit to the data (this is known as equifinality. Here we describe a method to estimate the firn diffusivity profile that allows multiple solutions to be identified, in order to quantify the uncertainty in diffusivity due to equifinality. We then look at how well different combinations of tracers constrain the firn diffusivity profile. Tracers with rapid atmospheric variations like CH3CCl3, HFCs and 14CO2 are most useful for constraining molecular diffusivity, while δ15N2 is useful for constraining parameters related to convective mixing near the surface. When errors in the observations are small and Gaussian, three carefully selected tracers are able to constrain the molecular diffusivity profile well with minimal equifinality. However, with realistic data errors or additional processes to constrain, there is benefit to including as many tracers as possible to reduce the uncertainties. We calculate CO2 age distributions and their spectral widths with uncertainties for five firn sites (NEEM, DE08-2, DSSW20K, South Pole 1995 and South Pole 2001 with quite different characteristics and tracers available for calibration. We recommend moving away from the use of a single firn model with one calibrated parameter set to infer atmospheric histories, and instead suggest using multiple parameter sets, preferably with multiple representations of uncertain processes, to allow quantification of the uncertainties.

  2. Synthesis of new derivatives of 21-imidazolyl-16-dehydropregnenolone as inhibitors of 5α-reductase 2 and with cytotoxic activity in cancer cells.

    Science.gov (United States)

    Silva-Ortiz, Aylin Viviana; Bratoeff, Eugene; Ramírez-Apan, Teresa; Heuze, Yvonne; Soriano, Juan; Moreno, Isabel; Bravo, Marisol; Bautista, Lucero; Cabeza, Marisa

    2017-03-01

    The aim of this study was to synthesize several 16-dehydropregnenolone derivatives containing an imidazole ring at C-21 and a different ester moiety at C-3 as inhibitors of 5α-reductase 1 and 2 isoenzymes. Their binding capacity to the androgen receptor (AR) was also studied. Additionally, we evaluated their pharmacological effect in a castrated hamster model and their cytotoxic activity on a panel of cancer cells (PC-3, MCF7, SK-LU-1). The results showed that only the derivatives with an alicyclic ester at C-3 showed 5α-R2 enzyme inhibition activity, the most potent of them being 21-(1H-imidazol-1-yl)-20-oxopregna-5,16-dien-3β-yl-cyclohexanecarboxylate with an IC50 of 29nM. This is important because prostatic benign hyperplasia is directly associated with the presence of 5α-R2. However, all the derivatives failed to inhibit 5α-R1 or bind to the AR. These alicyclic ester derivatives decreased the weight and size of androgen-dependent glands in the hamster, indicating they are very active in vivo and are not toxic. In addition, the 21-(1H-imidazol-1-yl)-20-oxopregna-5,16-dien-3β-yl-acetate derivative showed the highest cytotoxic activity on the three cancer cell lines studied. It is therefore important in the synthesis of steroidal compounds to consider the size of the ester moiety at C-3 of the steroid skeleton, which is key in obtaining biological activity, as observed in this experiment.

  3. Synthesis and biodistribution of novel magnetic-poly(HEMA-APH) nanopolymer radiolabeled with iodine-131 and investigation its fate in vivo for cancer therapy

    Science.gov (United States)

    Avcıbaşı, Uğur; Avcıbaşı, Nesibe; Akalın, Hilmi Arkut; Ediz, Melis; Demiroğlu, Hasan; Gümüşer, Fikriye Gül; Özçalışkan, Emir; Türkcan, Ceren; Uygun, Deniz Aktaş; Akgöl, Sinan

    2013-10-01

    Herein, we investigated the biological uptake, distribution, and radiopharmaceutical potential of a novel molecule based on 2-hydroxyethyl methacrylate (HEMA) and anilinephtalein (APH) in the metabolism of Albino Wistar rats. In order to achieve this, we synthesized APH using organic synthesis methods and copolymerized APH with HEMA using a common polymerization method, surfactant-free emulsion polymerization. In the presence of Fe3O4 particles, we obtained a new generation magnetic-nano-scale polymer, magnetic-poly(HEMA-APH). This new molecule was chemically identified and approved by several characterization methods using Fourier transform infrared spectroscopy, scanning electron microscope, energy dispersive X-ray spectroscopy, electron spin resonance, atomic force microscope, and Zeta particle-size analysis. To evaluate the biological activity in live metabolism and anti-cancer potential of mag-poly(HEMA-APH), molecule was radioiodinated by a widely used labeling technique, iodogen method, with a gamma diffuser radionuclide, 131I. Thin-layer radiochromatography experiments demonstrated that 131I binded to nanopolymer with the labeling yield of 90 %. Lipophilicity and stability experiments were conducted to determine the condition of cold and labeled mag-poly(HEMA-APH) in rat blood and lipid medium. Results demonstrated that radioiodinated molecule stayed as an intact complex in rat metabolism for 24 h and experimental lipophilicity was determined as 0.12 ± 0.02. In vivo results obtained by imaging and biological distribution experiments indicated that mag-poly(HEMA-APH) labeled with 131I [131I-mag-poly(HEMA-APH)] highly incorporated into tissues of the uterus, the ovarian, the prostate, and the lungs in rat metabolism. Based on these results, it may be evaluated that novel mag-poly(HEMA-APH) molecule labeled with 131I is a compound which has a significant potential for being used as an anti-cancer agent. Certain results can only be obtained whether this

  4. Synthesis, chemical characterization, computational studies and biological activity of new DNA methyltransferases (DNMTs) specific inhibitor. Epigenetic regulation as a new and potential approach to cancer therapy.

    Science.gov (United States)

    Pellerito, C; Morana, O; Ferrante, F; Calvaruso, G; Notaro, A; Sabella, S; Fiore, T

    2015-09-01

    This work deals with the synthesis, the chemical characterization of dibutyltin(IV) complex of caffeic acid (Bu2Sn(IV)HCAF, caf1) and its cytotoxic action on tumor cells. The coordination environment at the tin center was investigated by FTIR, (119)Sn{(1)H} cross polarization magic angle spinning, electrospray ionization mass spectroscopy in the solid state and UV-vis, fluorescence and (1)H, (13)C and (119)Sn NMR spectroscopy in solution phases. Density functional theory study confirmed the proposed structures in solution phase and indicated the most probably stable conformation. The effects on viability of breast cancer MDA-MB231, colorectal cancer HCT116, hepatocellular carcinoma HepG2 and Chang liver cells, an immortalized non-tumor hepatic cell line, have been investigated. The effect of a variation in structure of caf1 was found to lead to a change in the respective antiproliferative properties: caf1 induces loss of viability in HCT116, MDA-MB-231, and HepG2; the complex shows only moderate effects in non-tumor Chang liver cells. caf1 exerts lower cytotoxic activity than Bu2SnCl2, suggesting that the binding with H3CAF modulates the marked cytotoxic activity exerted by Bu2SnCl2; caf1 displays a considerably more pronounced antitumoural effect towards cell lines than caffeic acid. It is known that caffeic acid can modulate DNA (cytosine-5)-methyltransferases 1 (DNMT1) mediated DNA methylation. In this paper we demonstrate that caf1 treatment was able to induce a time-dependent reduction of global DNA methylated status. This effect was also confirmed by a concomitant reduction DNMT1 expression level. The effect induced by caf1 was more evident not only with respect to untreated cells but also compared to H3CAF treated cells.

  5. Biochemical synthesis of silver nanoprticles using filamentous fungi Penicillium decumbens (MTCC-2494) and its efficacy against A-549 lung cancer cell line.

    Science.gov (United States)

    Majeed, Shahnaz; Abdullah, Mohd Syafiq Bin; Dash, Gouri Kumar; Ansari, Mohammed Tahir; Nanda, Anima

    2016-08-01

    Biosynthesis of silver and other metallic nanoparticles is one of the emerging research area in the field of science and technology due to their potentiality, especially in the field of nano-biotechnology and biomedical sciences in order to develop nanomedicine. In our present study, Penicillium decumbens (MTCC-2494) was brought from Institute of Microbial Technology (IMTECH) Chandigarh and employed for extracellular biological synthesis of silver nanoparticles. Ag-NPs formation was appeared with a dark brown color inside the conical flask. Characterization of Ag-NPs were done by UV-Spectrophotometric analysis which showed absorption peak at 430 nm determines the presence of nanoparticles, Fourier transform infrared (FT-IR) spectroscopic analysis, showed amines and amides are the possible proteins involved in the stabilization of nanoparticles as capping agent. Atomic force Microscopy (AFM) confirmed the particle are spherical, size was around 30 to 60 nm and also the roughness of nanoparticles. Field emission scanning electron microscopy (FE-SEM) showed the topology of the nanoparticles and were spherical in shape. The biosynthesis process was found fast, ecofriendly and cost effective. Nano-silver particle was found to have a broad antimicrobial activity and also it showed good enhancement of antimicrobial activity of Carbenicillin, Piperacillin, Cefixime, Amoxicillin, Ofloxacin and Sparfloxacin in a synergistic mode. These Ag-NPs showed good anti-cancer activity at 80 μg·mL(-1)upon 24 hours of incubation and toxicity increases upon 48 hours of incubation against A-549 human lung cancer cell line and the synergistic formulation of the antibiotic with the synthesized nanoparticles was found more effective against the pathogenic bacteria studied.

  6. Breakthrough cancer pain (BTcP): a synthesis of taxonomy, pathogenesis, therapy, and good clinical practice in adult patients in Italy.

    Science.gov (United States)

    Zucco, Furio; Bonezzi, Cesare; Fornasari, Diego

    2014-07-01

    Pain presents in 80% of patients with advanced cancer, and 30% have periods of increased pain due to fluctuating intensity, known as breakthrough cancer pain (BTcP). BTcP is high-intensity, short-duration pain occurring in several episodes per day and is non-responsive to treatment. The clinical approach to BTcP is variable. A review of the literature was performed to provide clinicians and practitioners with a rational synthesis of the ongoing scientific debate on BTcP and to provide a basis for optimal clinical approach to BTcP in adult Italian patients. Data show that circadian exacerbations of pain should be carefully monitored, differentiating, if possible, between fluctuations of background pain (BP), end-of-dose effect, and BTcP. BTcP should be monitored in all care contexts in clinical practice and each care facility must have all the medications and products approved for use in BTcP at their disposal. Data show that knowledge about medications for BTcP is lacking: medications for BTcP treatment are not interchangeable, although containing the same active substance; each physician must know the specific characteristics of each medication, its pharmacological properties, limitations in clinical practice, specifics relating to titration and repeatability of administration, and technical specifics relating to the accessibility and delivery. Importantly, before choosing a rapid-onset opioid (ROO), it is essential to deeply understand the status of patient and the characteristics of their family unit/caregivers, taking into account the patient's progressive loss of autonomy and/or cognitive-relational functionality. When BTcP therapy is initiated or changed, special attention must be paid to training the patient and family members/caregivers, providing clear instructions regarding the timing of drug administration. The patient must already be treated effectively with opioids before introducing ROOs for control of BTcP.

  7. Observation of individual tracer atoms in an ultracold dilute gas

    CERN Document Server

    Hohmann, Michael; Lausch, Tobias; Mayer, Daniel; Schmidt, Felix; Lutz, Eric; Widera, Artur

    2016-01-01

    Understanding the motion of a tracer particle in a rarefied gas is of fundamental and practical importance. We report the experimental investigation of individual Cs atoms impinging on a dilute cloud of ultracold Rb atoms with variable density. We study the nonequilibrium relaxation of the initial nonthermal state and detect the effect of single collisions which has eluded observation so far. We show that after few collisions, the measured spatial distribution of the light tracer atoms is correctly described by a generalized Langevin equation with a velocity-dependent friction coefficient, over a large range of Knudsen numbers.

  8. Tracer Cycles and Water Ages in Heterogeneous Catchments and Aquifers

    Science.gov (United States)

    Kirchner, J. W.; Jasechko, S.

    2015-12-01

    Estimates of catchment mean transit times are often based on seasonal cycles of stable isotope tracers in precipitation and streamflow. In many cases these transit time estimates are derived directly from sine-wave fitting to the observed seasonal isotope cycles. Broadly similar results are also obtained from time-domain convolutions or explicit tracer modeling, because here too the dominant tracer signal that these techniques seek to match is the seasonal isotopic cycle. Here I use simple benchmark tests to show that estimates of mean transit times based on seasonal tracer cycles will typically be wrong by several hundred percent, when applied to catchments with realistic degrees of spatial heterogeneity. This aggregation bias arises from the strong nonlinearity in the relationship between tracer cycle amplitude and mean travel time. A similar bias arises in estimates of mean transit times in nonstationary catchments. Since typical real-world catchments are both spatially heterogeneous and nonstationary, this analysis poses a fundamental challenge to tracer-based estimates of mean transit times. I propose an alternative storage metric, the fraction of "young water" in streamflow, defined as the fraction of runoff with transit times of less than roughly 0.2 years. I show that young water fractions are virtually free of aggregation bias; that is, they can be accurately estimated from tracer cycles in highly heterogeneous mixtures of subcatchments with strongly contrasting transit time distributions. They can also be reliably estimated in strongly nonstationary catchments. Young water fractions can be estimated separately for individual flow regimes, allowing direct determination of how shifts in hydraulic regime alter the fraction of water reaching the stream by fast flowpaths. One can also estimate the chemical composition of idealized "young water" and "old water" end-members, using relationships between young water fractions and solute concentrations across

  9. Preliminary assessment of halogenated alkanes as vapor-phase tracers

    Energy Technology Data Exchange (ETDEWEB)

    Adams, Michael C.; Moore, Joseph N.; Hirtz, Paul

    1991-01-01

    New tracers are needed to evaluate the efficiency of injection strategies in vapor-dominated environments. One group of compounds that seems to meet the requirements for vapor-phase tracing are the halogenated alkanes (HCFCs). HCFCs are generally nontoxic, and extrapolation of tabulated thermodynamic data indicate that they will be thermally stable and nonreactive in a geothermal environment. The solubilities and stabilities of these compounds, which form several homologous series, vary according to the substituent ratios of fluorine, chlorine, and hydrogen. Laboratory and field tests that will further define the suitability of HCFCs as vapor-phase tracers are under way.

  10. Rebuilding sources of linear tracers after atmospheric concentration measurements

    Directory of Open Access Journals (Sweden)

    J.-P. Issartel

    2003-01-01

    Full Text Available The identification of widespread sources of passive tracers out of atmospheric concentration measurements has become an important challenge of modern meteorology. The paper proposes some mathematical tracks to address the reconstruction of the complex space-time geometry of the sources of linear tracers. The methods are based upon the use of retroplumes. The inverse problem is addressed in a deterministic non statistical frame. The information obtained by local measurements is spread by introducing the concept of illumination. The constraint that the source is non negative is also addressed. The experimental source ETEX1 is rebuilt in order to evaluate an impulse response of the algorithms.

  11. Beta-lactam type molecular scaffolds for antiproliferative activity: synthesis and cytotoxic effects in breast cancer cells.

    Science.gov (United States)

    Meegan, Mary J; Carr, Miriam; Knox, Andrew J S; Zisterer, Daniela M; Lloyd, David G

    2008-10-01

    A series of novel beta-lactam containing compounds are described as antiproliferative agents and potential selective modulators of the oestrogen receptor. The purpose of the study is to evaluate the antiproliferative effects of these compounds on human MCF-7 and MDA MB-231 breast cancer cells. The compounds are designed to contain three aryl ring substituents arranged on the heterocyclic azetidin-2-one (beta-lactam), thus providing conformationally restrained analogues of the triarylethylene arrangement exemplified in the tamoxifen type structure. The compounds demonstrated potency in antiproliferative assays against MCF-7 human breast cancer cell line at low micromolar to nanomolar concentrations with low cytotoxicity and moderate binding affinity to the oestrogen receptor. The effect of a number of aryl and amine functional group substitutions on the antiproliferative activity of the beta-lactam products was explored and a brief computational structure-activity relationship investigation with molecular simulation was investigated.

  12. Nanohybride Materials Based on Magnetite-Gold Nanoparticles for Diagnostics of Prostate Cancer: Synthesis and In Vitro Testing.

    Science.gov (United States)

    Machulkin, A E; Garanina, A S; Zhironkina, O A; Beloglazkina, E K; Zyk, N V; Savchenko, A G; Kotelyanskii, V E; Mazhuga, A G

    2016-09-01

    We synthesized a fluorescence conjugate and modified magnetite-gold nanoparticles carrying prostate specific membrane antigen (PSMA) as the ligand. Analysis of their binding to human prostate cancer cell lines PC-3 (PSMA(-)) and LNCaP (PSMA(+)) showed selective interaction of the synthesized conjugate and modified nanoparticles with LNCaP cells. These findings suggest that these nanoparticles can be used in tissue-specific magnetic-resonance imaging.

  13. Conductive polymer-based nanoparticles for laser-mediated photothermal ablation of cancer: synthesis, characterization, and in vitro evaluation

    OpenAIRE

    Cantu T; Walsh K; Pattani VP; Moy AJ; Tunnell JW; Irvin JA; Betancourt T

    2017-01-01

    Travis Cantu,1 Kyle Walsh,2 Varun P Pattani,3 Austin J Moy,3 James W Tunnell,3 Jennifer A Irvin,1,2 Tania Betancourt1,2 1Materials Science, Engineering, and Commercialization Program, Texas State University, San Marcos, TX, USA; 2Department of Chemistry and Biochemistry, Texas State University, San Marcos, TX, USA; 3Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX, USA Abstract: Laser-mediated photothermal ablation of cancer cells aided by photothermal age...

  14. Facile synthesis of 2-D Cu doped WO3 nanoplates with structural, optical and differential anti cancer characteristics

    Science.gov (United States)

    Mehmood, Faisal; Iqbal, Javed; Gul, Asma; Ahmed, Waqqar; Ismail, M.

    2017-04-01

    Simple chemical co-precipitation method has been employed to synthesize two dimensional copper (Cu) doped tungsten oxide (WO3) nanoplates. A numbers of characterization techniques have been used to investigate their structural, optical and biocompatible anti cancer properties. The XRD results have confirmed the monoclinic crystal structure of WO3 nanoplates, and also successful doping of Cu ions into the WO3 crystal lattice. The presence of functional groups and chemical bonding have been verified through FTIR and Raman spectroscopy. The SEM images demonstrate that both undoped and Cu doped WO3 samples have squares plate like morphology. The EDX spectra confirm the presence of Cu, W and O ions. Diffuse reflectance spectroscopy (DRS) analysis has revealed a substantial red-shift in the absorption edge and a decrease in the band gap energy of nanoplates with Cu doping. Photoluminescence spectroscopy has been used to study the presence of defects like oxygen vacancies. Furthermore, the differential cytotoxic properties of Cu doped WO3 samples have been evaluated against human breast (MCF-7) and liver (Hep-2) cancer cells with ectocervical epithelial (HECE) healthy cells. The present findings confirm that the Cu doped WO3 nanoplates can be used as an efficient biocompatible anti cancer agent.

  15. Synthesis and anticancer activity of novel benzimidazole and benzothiazole derivatives against HepG2 liver cancer cells.

    Science.gov (United States)

    Youssef, Amal M; Malki, Ahmed; Badr, Mona H; Elbayaa, Rasha Y; Sultan, Ahmed S

    2012-03-01

    Most of cancer chemotherapeutics and chemopreventives exert their effects by triggering apoptotic cell death. In this study, novel benzimidazole and benzothiazole derivatives have been synthesized to investigate their effects on HepG2 liver cancer cell lines after initial screening study. A dose response curve was constructed and the most active derivatives were further studied for apoptotic analysis. Six active benzimidazole derivatives (8, 9, 10, 12, 13 and 14) significantly induced apoptosis compared to control group. Two compounds 10 and 12 induced apoptosis by arresting cells in G1 phase of cell cycle which is confirmed by increased expression level of p21. The activity of caspase-3 which is well known as one of the key executioners of apoptosis was determined in the presence and absence of the tested derivatives. Our results indicated that compounds 10 and 12 significantly increased caspase-3 activity compared to control group. Moreover, a docked pose of compounds 10 and 12 was obtained bound to caspase-3 active site using Molecular Operating Environment module. This study demonstrated that benzimidazole derivatives 10 and 12 provoke cytotoxicity and induced apoptosis in liver cancer cells HepG2.

  16. Hope and challenge: the importance of ultraviolet (UV) radiation for cutaneous vitamin D synthesis and skin cancer.

    Science.gov (United States)

    Reichrath, Jörg; Reichrath, Sandra

    2012-01-01

    Abstract Solar ultraviolet (UV)-radiation is the most important environmental risk factor for the development of non-melanoma skin cancer (most importantly basal and squamous cell carcinomas), that represent the most common malignancies in Caucasian populations. To prevent these malignancies, public health campaigns were developed to improve the awareness of the general population of the role of UV-radiation. The requirements of vitamin D is mainly achieved by UV-B-induced cutaneous photosynthesis, and the vitamin D-mediated positive effects of UV-radiation were not always adequately considered in these campaigns; a strict "no sun policy" might lead to vitamin D-deficiency. This dilemma represents a serious problem in many populations, for an association of vitamin D-deficiency and multiple independent diseases has been convincingly demonstrated. It is crucial that guidelines for UV-exposure (e.g. in skin cancer prevention campaigns) consider these facts and give recommendations how to prevent vitamin D-deficiency. In this review, we analyze the present literature to help developing well-balanced guidelines on UV-protection that ensure an adequate vitamin D-status without increasing the risk to develop UV-induced skin cancer.

  17. Sentinel Node in Oral Cancer

    DEFF Research Database (Denmark)

    Tartaglione, Girolamo; Stoeckli, Sandro J; de Bree, Remco;

    2016-01-01

    PURPOSE: Nuclear imaging plays a crucial role in lymphatic mapping of oral cancer. This evaluation represents a subanalysis of the original multicenter SENT trial data set, involving 434 patients with T1-T2, N0, and M0 oral squamous cell carcinoma. The impact of acquisition techniques, tracer...

  18. Experiments to Evaluate and Implement Passive Tracer Gas Methods to Measure Ventilation Rates in Homes

    Energy Technology Data Exchange (ETDEWEB)

    Lunden, Melissa [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Faulkner, David [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Heredia, Elizabeth [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Cohn, Sebastian [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Dickerhoff, Darryl [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Noris, Federico [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Logue, Jennifer [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Hotchi, Toshifumi [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Singer, Brett [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Sherman, Max H. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2012-10-01

    This report documents experiments performed in three homes to assess the methodology used to determine air exchange rates using passive tracer techniques. The experiments used four different tracer gases emitted simultaneously but implemented with different spatial coverage in the home. Two different tracer gas sampling methods were used. The results characterize the factors of the execution and analysis of the passive tracer technique that affect the uncertainty in the calculated air exchange rates. These factors include uncertainties in tracer gas emission rates, differences in measured concentrations for different tracer gases, temporal and spatial variability of the concentrations, the comparison between different gas sampling methods, and the effect of different ventilation conditions.

  19. Nanomedicine and cancer therapies

    CERN Document Server

    Sebastian, Mathew; Elias, Eldho

    2012-01-01

    Introduction Nanotechnological-Based Systems for CancerIn vivo Spectroscopy for Detection and Treatment of GBM with NPt® ImplantationNanobiotechnology for Antibacterial Therapy and DiagnosisChitosan NanoparticlesSynthesis and Biomedical Application of Silver NanoparticlesRecent Advances in Cancer Therapy Using PhytochemicalsMitochondrial Dysfunction and Cancer: Modulation by Palladium-Lipoic Acid ComplexUnity of Mind and Body: The Concept of Life Purpose DominantThuja Occidentalis and Breast Cancer ChemopreventionAntioxidants and Com

  20. Evolutionary theory of cancer.

    Science.gov (United States)

    Attolini, Camille Stephan-Otto; Michor, Franziska

    2009-06-01

    As Theodosius Dobzhansky famously noted in 1973, "Nothing in biology makes sense except in the light of evolution," and cancer is no exception to this rule. Our understanding of cancer initiation, progression, treatment, and resistance has advanced considerably by regarding cancer as the product of evolutionary processes. Here we review the literature of mathematical models of cancer evolution and provide a synthesis and discussion of the field.

  1. ROBOTIC SYNTHESIS OF L-[1-C-11]TYROSINE

    NARCIS (Netherlands)

    LUURTSEMA, G; MEDEMA, J; ELSINGA, PH; VISSER, GM; VAALBURG, W

    1994-01-01

    L-[1-C-11]tyrosine promises to become an important tracer for determination of the protein synthesis rate (PSR) in tumor tissue and brain. The commercially available Anatech RB-86 robotic system is utilized for the automation of the L-[1-C-11]tyrosine production via the isocyanide method as reported

  2. Unit vent airflow measurements using a tracer gas technique

    Energy Technology Data Exchange (ETDEWEB)

    Adams, D.G. [Union Electric Company, Fulton, MO (United States); Lagus, P.L. [Lagus Applied Technology, Inc., San Diego, CA (United States); Fleming, K.M. [NCS Corp., Columbus, OH (United States)

    1997-08-01

    An alternative method for assessing flowrates that does not depend on point measurements of air flow velocity is the constant tracer injection technique. In this method one injects a tracer gas at a constant rate into a duct and measures the resulting concentration downstream of the injection point. A simple equation derived from the conservation of mass allows calculation of the flowrate at the point of injection. Flowrate data obtained using both a pitot tube and a flow measuring station were compared with tracer gas flowrate measurements in the unit vent duct at the Callaway Nuclear Station during late 1995 and early 1996. These data are presented and discussed with an eye toward obtaining precise flowrate data for release rate calculations. The advantages and disadvantages of the technique are also described. In those test situations for which many flowrate combinations are required, or in large area ducts, a tracer flowrate determination requires fewer man-hours than does a conventional traverse-based technique and does not require knowledge of the duct area. 6 refs., 10 figs., 6 tabs.

  3. Diagnostic Implications of the Reactivity of Fluorescence Tracers

    Energy Technology Data Exchange (ETDEWEB)

    Sick, V; Westbrook, C

    2008-07-14

    Measurements of fuel concentration distributions with planar laser induced fluorescence of tracer molecules that are added to a base fuel are commonly used in combustion research and development. It usually is assumed that the tracer concentration follows the parent fuel concentration if physical properties such as those determining evaporation are matched. As an example to address this general issue a computational study of combustion of biacetyl/iso-octane mixtures was performed to investigate how well the concentration of biacetyl represents the concentration of iso-octane. For premixed mixture conditions with flame propagation the spatial concentration profiles of the two species in the flame front are separated by 110 {micro}m at 1 bar and by 11 {micro}m at 10 bar. For practical applications this spatial separation is insignificantly small. However, for conditions that mimic ignition and combustion in diesel and HCCI-like operation the differences in tracer and fuel concentration can be significant, exceeding hundreds of percent. At low initial temperature biacetyl was found to be more stable whereas at higher temperature (>1000K) iso-octane is more stable. Similar findings were obtained for a multi-component fuel comprised of iso-octane, n-heptane, methylcyclohexane, and toluene. It may be assumed that similar differences can exist for other tracer/fuel combinations. Caution has therefore to be applied when interpreting PLIF measurements in homogeneous reaction conditions such as in HCCI engine studies.

  4. Tracer Studies In A Laboratory Beach Subjected To Waves

    Science.gov (United States)

    This work investigated the washout of dissolved nutrients from beaches due to waves by conducting tracer studies in a laboratory beach facility. The effects of waves were studied in the case where the beach was subjected to the tide, and that in which no tidal action was present...

  5. Uptake and transport of positron-emitting tracer in plants

    Energy Technology Data Exchange (ETDEWEB)

    Kume, Tamikazu; Matsuhashi, Shinpei; Shimazu, Masamitsu [Japan Atomic Energy Research Inst., Takasaki, Gunma (Japan). Takasaki Radiation Chemistry Research Establishment] [and others

    1997-03-01

    The transport of a positron-emitting isotope introduced into a plant was dynamically followed by a special observation apparatus called `Positron-Emitting Tracer Imaging System`. In the system, annihilation {gamma}-rays from the positron emitter are detected with two planer detectors (5 x 6 cm square). The water containing ca. 5 MBq/ml of {sup 18}F was fed to the cut stem of soybean for 2 min and then the images of tracer activity were recorded for 30 - 50 min. When the midrib of a leaf near the petiole was cut just before measurement, the activity in the injured leaf was decreased but detected even at the apex. This result suggests that the damaged leaf recovered the uptake of water through the lamina. Maximum tracer activities in leaves of unirradiated plant were observed within 10 min, whereas those of irradiated plant at 100 Gy were observed after over 25 min. The final activity of irradiated plant after 30 min was lower than that of unirradiated plant. In case of beans, there was a difference in the absorption behavior of the {sup 18}F-labeled water between unirradiated and irradiated samples. These results show that the system is effective to observe the uptake and transportation of water containing positron emitting tracer for the study of damage and recovery functions of plants. (author)

  6. Correlative microscopy of densely labeled projection neurons using neural tracers.

    Science.gov (United States)

    Oberti, Daniele; Kirschmann, Moritz A; Hahnloser, Richard H R

    2010-01-01

    Three-dimensional morphological information about neural microcircuits is of high interest in neuroscience, but acquiring this information remains challenging. A promising new correlative technique for brain imaging is array tomography (Micheva and Smith, 2007), in which series of ultrathin brain sections are treated with fluorescent antibodies against neurotransmitters and synaptic proteins. Treated sections are repeatedly imaged in the fluorescence light microscope (FLM) and then in the electron microscope (EM). We explore a similar correlative imaging technique in which we differentially label distinct populations of projection neurons, the key routers of electrical signals in the brain. In songbirds, projection neurons can easily be labeled using neural tracers, because the vocal control areas are segregated into separate nuclei. We inject tracers into areas afferent and efferent to the main premotor area for vocal production, HVC, to retrogradely and anterogradely label different classes of projection neurons. We optimize tissue preparation protocols to achieve high fluorescence contrast in the FLM and good ultrastructure in the EM (using osmium tetroxide). Although tracer fluorescence is lost during EM preparation, we localize the tracer molecules after fixation and embedding by using fluorescent antibodies against them. We detect signals mainly in somata and dendrites, allowing us to classify synapses within a single ultrathin section as belonging to a particular type of projection neuron. The use of our method will be to provide statistical information about connectivity among different neuron classes, and to elucidate how signals in the brain are processed and routed among different areas.

  7. Correlative microscopy of densely labeled projection neurons using neural tracers

    Directory of Open Access Journals (Sweden)

    Daniele Oberti

    2010-06-01

    Full Text Available Three-dimensional morphological information about neural microcircuits is of high interest in neuroscience, but acquiring this information remains challenging. A promising new correlative technique for brain imaging is array tomography (Micheva and Smith, 2007, in which series of ultrathin brain sections are treated with fluorescent antibodies against neurotransmitters and synaptic proteins. Treated sections are repeatedly imaged in the fluorescence light microscope (FLM and then in the electron microscope (EM. We explore a similar correlative imaging technique in which we differentially label distinct populations of projection neurons, the key routers of electrical signals in the brain. In songbirds, projection neurons can easily be labeled using neural tracers, because the vocal control areas are segregated into separate nuclei. We inject tracers into areas afferent and efferent to the main premotor area for vocal production, HVC, to retrogradely and anterogradely label different classes of projection neurons. We optimize tissue preparation protocols to achieve high fluorescence contrast in the FLM and good ultrastructure in the EM (using osmium tetroxide. Although tracer fluorescence is lost during EM preparation, we localize the tracer molecules after fixation and embedding by using fluorescent antibodies against them. We detect signals mainly in somata and dendrites, allowing us to classify synapses within a single ultrathin section as belonging to a particular type of projection neuron. The use of our method will be to provide statistical information about connectivity among different neuron classes, and to elucidate how signals in the brain are processed and routed among different areas.

  8. 76 FR 71610 - Market Test of First-Class Tracer

    Science.gov (United States)

    2011-11-18

    ... research and development costs incurred in connection with new product development. Id. Statutory authority... product, First- Class Tracer. This document describes the proposed test, addresses procedural aspects of... a market test beginning on or about December 7, 2011, of an experimental market dominant...

  9. Carbon monoxide : A quantitative tracer for fossil fuel CO2?

    NARCIS (Netherlands)

    Gamnitzer, Ulrike; Karstens, Ute; Kromer, Bernd; Neubert, Rolf E. M.; Meijer, Harro A. J.; Schroeder, Hartwig; Levin, Ingeborg

    2006-01-01

    Carbon monoxide (CO), carbon dioxide (CO2), and radiocarbon ((CO2)-C-14) measurements have been made in Heidelberg from 2001 to 2004 in order to determine the regional fossil fuel CO2 component and to investigate the application of CO as a quantitative tracer for fossil fuel CO2 (CO2(foss)). The obs

  10. Tracer Modeling with the Hybrid Coordinates Ocean Model (hycom)

    Science.gov (United States)

    Garraffo, Z. D.; Kim, H.; Li, B.; Mehra, A.; Rivin, I.; Spindler, T.; Tolman, H. L.

    2012-12-01

    A series of tracer simulations have been started at NCEP/NWS aiming to a variety of applications, from dispersion of contaminants in estimations motivated by the Japanese nuclear accident near Fukushima, to nutrient estimations. The tracer capabilities of HYCOM are used, in regional domains, nested to daily nowcast/forecast fields from 1/12 HYCOM (RTOFS-Global) model output. A Fukushima Cs-137 simulation is now run in operational mode (RTOFS_ET). The simulation was initialized at the time of the Fukushima nuclear accident, and includes atmospheric deposition of Cs-137 and coastal discharge from a high resolution coastal model (ROMS done at NOAA/NOS). Almost all tracer moved offshore before the end of the first year after the accident. The tracer initially deposited in the Pacific ocean through the atmosphere slowly moves eastward and to deeper waters following the 3D ocean circulation. A series of simulations were started for nutrient estimations in the Gulf Stream and Mid Atlantic Bight region. Initially the capabilities implemented in HYCOM are used. The work aims to monitoring nutrients in the chosen region. Work is done in collaboration with Victoria Coles of U. Maryland.

  11. Granulation of Pyrotechnic Tracer Composition R284T

    Science.gov (United States)

    1988-03-01

    Properties of Materials used in Pyrotechnic Compositions (1963). Engineering Design Handbook - Military Pyrotechnic Series Part 3. AMPC 706-187. 4...Ml Cartridge AMPC 706-185 APPLICATION: Main Tracer Charge TM9-1910 Ellern STORAGE: NATO DoD McIntyre Hazards Class (Q/D 1.1 7 Cabbaje & Ewing

  12. Bridging the gaps in 18F PET tracer development

    Science.gov (United States)

    Campbell, Michael G.; Mercier, Joel; Genicot, Christophe; Gouverneur, Véronique; Hooker, Jacob M.; Ritter, Tobias

    2017-01-01

    As compared to the drug discovery process, the development of new 18F PET tracers lacks a well-established pipeline that advances compounds from academic research to candidacy for (pre)clinical imaging. In order to bridge the gaps between methodological advances and clinical success, we must rethink the development process from training to implementation.

  13. TRAC, a collaborative computer tool for tracer-test interpretation

    Science.gov (United States)

    Gutierrez, A.; Klinka, T.; Thiéry, D.; Buscarlet, E.; Binet, S.; Jozja, N.; Défarge, C.; Leclerc, B.; Fécamp, C.; Ahumada, Y.; Elsass, J.

    2013-05-01

    Artificial tracer tests are widely used by consulting engineers for demonstrating water circulation, proving the existence of leakage, or estimating groundwater velocity. However, the interpretation of such tests is often very basic, with the result that decision makers and professionals commonly face unreliable results through hasty and empirical interpretation. There is thus an increasing need for a reliable interpretation tool, compatible with the latest operating systems and available in several languages. BRGM, the French Geological Survey, has developed a project together with hydrogeologists from various other organizations to build software assembling several analytical solutions in order to comply with various field contexts. This computer program, called TRAC, is very light and simple, allowing the user to add his own analytical solution if the formula is not yet included. It aims at collaborative improvement by sharing the tool and the solutions. TRAC can be used for interpreting data recovered from a tracer test as well as for simulating the transport of a tracer in the saturated zone (for the time being). Calibration of a site operation is based on considering the hydrodynamic and hydrodispersive features of groundwater flow as well as the amount, nature and injection mode of the artificial tracer. The software is available in French, English and Spanish, and the latest version can be downloaded from the web site http://trac.brgm.fr">http://trac.brgm.fr.

  14. Synthesis of highly fluorescent nitrogen and phosphorus doped carbon dots for the detection of Fe(3+) ions in cancer cells.

    Science.gov (United States)

    Chandra, Soumen; Laha, Dipranjan; Pramanik, Arindam; Ray Chowdhuri, Angshuman; Karmakar, Parimal; Sahu, Sumanta Kumar

    2016-02-01

    Highly fluorescent nitrogen and phosphorus-doped carbon dots with a quantum yield 59% have been successfully synthesized from citric acid and di-ammonium hydrogen phosphate by single step hydrothermal method. The synthesized carbon dots have high solubility as well as stability in aqueous medium. The as-obtained carbon dots are well monodispersed with particle sizes 1.5-4 nm. Owing to a good tunable fluorescence property and biocompatibility, the carbon dots were applied for intercellular sensing of Fe(3+) ions as well as cancer cell imaging.

  15. Hydrothermal synthesis of titanium dioxide nanoparticles: mosquitocidal potential and anticancer activity on human breast cancer cells (MCF-7).

    Science.gov (United States)

    Murugan, Kadarkarai; Dinesh, Devakumar; Kavithaa, Krishnamoorthy; Paulpandi, Manickam; Ponraj, Thondhi; Alsalhi, Mohamad Saleh; Devanesan, Sandhanasamy; Subramaniam, Jayapal; Rajaganesh, Rajapandian; Wei, Hui; Kumar, Suresh; Nicoletti, Marcello; Benelli, Giovanni

    2016-03-01

    Mosquito vectors (Diptera: Culicidae) are responsible for transmission of serious diseases worldwide. Mosquito control is being enhanced in many areas, but there are significant challenges, including increasing resistance to insecticides and lack of alternative, cost-effective, and eco-friendly products. To deal with these crucial issues, recent emphasis has been placed on plant materials with mosquitocidal properties. Furthermore, cancers figure among the leading causes of morbidity and mortality worldwide, with approximately 14 million new cases and 8.2 million cancer-related deaths in 2012. It is expected that annual cancer cases will rise from 14 million in 2012 to 22 million within the next two decades. Nanotechnology is a promising field of research and is expected to give major innovation impulses in a variety of industrial sectors. In this study, we synthesized titanium dioxide (TiO2) nanoparticles using the hydrothermal method. Nanoparticles were subjected to different analysis including UV-Vis spectrophotometry, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), zeta potential, and energy-dispersive spectrometric (EDX). The synthesized TiO2 nanoparticles exhibited dose-dependent cytotoxicity against human breast cancer cells (MCF-7) and normal breast epithelial cells (HBL-100). After 24-h incubation, the inhibitory concentrations (IC50) were found to be 60 and 80 μg/mL on MCF-7 and normal HBL-100 cells, respectively. Induction of apoptosis was evidenced by Acridine Orange (AO)/ethidium bromide (EtBr) and 4',6-diamidino-2-phenylindole dihydrochloride (DAPI) staining. In larvicidal and pupicidal experiments conducted against the primary dengue mosquito Aedes aegypti, LC50 values of nanoparticles were 4.02 ppm (larva I), 4.962 ppm (larva II), 5.671 ppm (larva III), 6.485 ppm (larva IV), and 7.527 ppm (pupa). Overall, our results suggested that TiO2 nanoparticles may be considered as

  16. Assessment of Halon-1301 as a groundwater age tracer

    Science.gov (United States)

    Beyer, M.; van der Raaij, R.; Morgenstern, U.; Jackson, B.

    2015-06-01

    Groundwater dating is an important tool to assess groundwater resources in regards to their dynamics, i.e. direction and timescale of groundwater flow and recharge, contamination risks and manage remediation. To infer groundwater age information, a combination of different environmental tracers, such as tritium and SF6, are commonly used. However, ambiguous age interpretations are often faced, due to a limited set of available tracers and their individual restricted application ranges. For more robust groundwater dating multiple tracers need to be applied complementarily (or other characterisation methods need to be used to complement tracer information). It is important that additional, groundwater age tracers are found to ensure robust groundwater dating in future. We have recently suggested that Halon-1301, a water soluble and entirely anthropogenic gaseous substance, may be a promising candidate, but its behaviour in water and suitability as a groundwater age tracer had not yet been assessed in detail. In this study, we determined Halon-1301 and inferred age information in 17 New Zealand groundwater samples and various modern (river) water samples. The samples were simultaneously analysed for Halon-1301 and SF6, which allowed for identification of issues such as contamination of the water with modern air during sampling. All analysed groundwater sites had also been previously dated with tritium, CFC-12, CFC-11 and SF6, and exhibited mean residence times ranging from modern (close to 0 years) to over 100 years. The investigated groundwater samples ranged from oxic to highly anoxic. All samples with available CFC data were degraded and/or contaminated in one or both of CFC-11 and CFC-12. This allowed us to make a first attempt of assessing the conservativeness of Halon-1301 in water, in terms of presence of local sources and its sensitivity towards degradation, which could affect the suitability of Halon-1301 as groundwater age tracer. Overall we found Halon-1301

  17. Texture Analysis and Synthesis of Malignant and Benign Mediastinal Lymph Nodes in Patients with Lung Cancer on Computed Tomography

    Science.gov (United States)

    Pham, Tuan D.; Watanabe, Yuzuru; Higuchi, Mitsunori; Suzuki, Hiroyuki

    2017-02-01

    Texture analysis of computed tomography (CT) imaging has been found useful to distinguish subtle differences, which are in- visible to human eyes, between malignant and benign tissues in cancer patients. This study implemented two complementary methods of texture analysis, known as the gray-level co-occurrence matrix (GLCM) and the experimental semivariogram (SV) with an aim to improve the predictive value of evaluating mediastinal lymph nodes in lung cancer. The GLCM was explored with the use of a rich set of its derived features, whereas the SV feature was extracted on real and synthesized CT samples of benign and malignant lymph nodes. A distinct advantage of the computer methodology presented herein is the alleviation of the need for an automated precise segmentation of the lymph nodes. Using the logistic regression model, a sensitivity of 75%, specificity of 90%, and area under curve of 0.89 were obtained in the test population. A tenfold cross-validation of 70% accuracy of classifying between benign and malignant lymph nodes was obtained using the support vector machines as a pattern classifier. These results are higher than those recently reported in literature with similar studies.

  18. Rational design and synthesis of novel anti-prostate cancer agents bearing a 3,5-bis-trifluoromethylphenyl moiety.

    Science.gov (United States)

    Ferla, Salvatore; Bassetto, Marcella; Pertusati, Fabrizio; Kandil, Sahar; Westwell, Andrew D; Brancale, Andrea; McGuigan, Christopher

    2016-08-01

    Prostate cancer is a major cause of male death worldwide and the identification of new and improved treatments is constantly required. Among the available options, different non-steroidal androgen receptor (AR) antagonists are approved also to treat castration-resistant forms. Most of these drugs show limited application due to the development of resistant mutants of their biological target. Following docking-based studies on a homology model for the AR open antagonist conformation, a series of novel 3,5-bis-trifluoromethylphenyl compounds was designed with the aim to improve the antiproliferative activity of anti-androgen drugs bicalutamide and enzalutamide. The new structural modifications might impede the receptor to adopt its closed agonist conformation also in the presence of adaptive mutations. Among the novel compounds synthesised, several displayed significantly improved in vitro activity in comparison with the parent structures, with IC50 values in the low micromolar range against four different prostate cancer cell lines (LNCaP, VCaP, DU-145, 22Rv1). Selected hits demonstrated full AR antagonistic behaviour and promising candidates for further development were identified.

  19. Synthesis of microtubule-interfering halogenated noscapine analogs that perturb mitosis in cancer cells followed by cell death.

    Science.gov (United States)

    Aneja, Ritu; Vangapandu, Surya N; Lopus, Manu; Viswesarappa, Vijaya G; Dhiman, Neerupma; Verma, Akhilesh; Chandra, Ramesh; Panda, Dulal; Joshi, Harish C

    2006-08-14

    We have previously identified the naturally occurring non-toxic antitussive phthalideisoquinoline alkaloid, noscapine as a tubulin-binding agent that arrests mitosis and induces apoptosis. Here we present high-yield efficient synthetic methods and an evaluation of anticancer activity of halogenated noscapine analogs. Our results show that all analogs display higher tubulin-binding activity than noscapine and inhibit proliferation of human cancer cells (MCF-7, MDA-MB-231 and CEM). Surprisingly, the bromo-analog is approximately 40-fold more potent than noscapine in inhibiting cellular proliferation of MCF-7 cells. The ability of these analogs to inhibit cellular proliferation is mediated by cell cycle arrest at the G2/M phase, in that all analogs except 9-iodonoscapine, caused selective mitotic arrest with a higher efficiency than noscapine followed by apoptotic cell death as shown by immunofluorescence and quantitative FACS analyses. Furthermore, our results reveal the appearance of numerous fragmented nuclei as evidenced by DAPI staining. Thus, our data indicate a great potential of these compounds for studying microtubule-mediated processes and as chemotherapeutic agents for the management of human cancers.

  20. Design and synthesis of 4-substituted quinazolines as potent EGFR inhibitors with anti-breast cancer activity.

    Science.gov (United States)

    Ahmed, Marwa; Magdy, Naja

    2016-09-23

    Cancer is a major health problem to human beings around the world. Many quinazoline derivatives were reported to have potent cytotoxic activity. Our aim in this work is the discovery of potent epidermal growth factor receptor (EGFR) inhibitors with anti-breast cancer activity containing 4-substituted quinazoline pharmacophore. Novel series of 4-substituted 6,8-dibromo-2-(4-chlorophenyl)-quinazoline derivatives have been designed and synthesized. New derivatives were tested against MCF-7 (human breast carcinoma cell line) and screened for their inhibition activity against epidermal growth factor receptor tyrosine kinase (EGFR-TK). Most of the tested compounds show potent antiproliferative activity and EGFR-TK inhibitory activity. Compounds VIIIc and VIIIb exerted powerful cytotoxic activity (IC50 3.1 and 6.3 µM) with potent inhibitory percent (91.1 and 88.4%) against EGFR-TK. Compounds IX, VIIa, X, VIIb, VIc, V, IV, VIa and VIb showed promising cytotoxic effects with IC50 range (12-79 µM) with good activity against EGFR-TK with the inhibitory percent (85.4-60.8%). On the other hand, compounds VIIc, VIIIa exerted low cytotoxic effects as revealed from their IC50 value (124 and 144 µM) with low activity against EGFR-TK with inhibitory percent 30.6 and 29.1% respectively.

  1. Synthesis, characterization and in vitro anti-cancer evaluation of hesperetin-loaded nanoparticles in human oral carcinoma (KB) cells

    Science.gov (United States)

    Gurushankar, K.; Gohulkumar, M.; Rajendra Prasad, N.; Krishnakumar, N.

    2014-03-01

    Hesperetin (HET), a naturally occurring plant bioflavonoid present in citrus fruits, possesses potential anti-inflammatory and anti-carcinogenic activities but poor aqueous solubility limits its applications. To improve its applicability in cancer therapy, hesperetin was encapsulated in Eudragit® E (EE) 100 nanoparticles in the presence of polyvinyl alcohol (PVA) as a stabilizer and its anticancer efficacy in oral carcinoma (KB) cells was studied. Hesperetin-loaded nanoparticles (HETNPs) were prepared by nanoprecipitation method and characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), Fourier transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), and x-ray diffraction (XRD). The results thus displayed that the prepared nanoparticles showed a particle size in the range from 55 to 180 nm. The encapsulation efficiency of hesperetin was 83.4% obtained by UV spectroscopy. The in vitro release kinetics of hesperetin under physiological condition show initial rapid release followed by slow and sustained release. 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide (MTT) assay revealed higher cytotoxic efficacy of HETNPs than native hesperetin in KB cells. Further, it has been found that reactive oxygen species (ROS) generation, DNA damage and apoptotic indices in HETNPs treated cells are greater than those in native hesperetin treatment. Hence these findings demonstrate that HETNPs could be a potentially useful drug delivery system to produce better hesperetin therapeutics of cancers.

  2. Hydroxy, carboxylic and amino acid functionalized superparamagnetic iron oxide nanoparticles: Synthesis, characterization and in vitro anti-cancer studies

    Indian Academy of Sciences (India)

    Dilaveez Rehana; Azees Khan Haleel; Aziz Kalilur Rahiman

    2015-07-01

    Superparamagnetic iron oxide nanoparticles were synthesized by simple co-precipitation method and modified with different coating agents such as ascorbic acid, hexanoic acid, salicylic acid, L-arginine and L-cysteine. The synthesized nanoparticles were characterized by various techniques such as FT IR, XRD, VSM, SEM, TEM and thermal analysis. Both bare and coated magnetites were of cubic spinel structure and spherical in shape. All the magnetite nanoparticles showed superparamagnetic behaviour with high saturated magnetization. In vitro cytotoxicity test of bare and coated nanoparticles was performed using adenocarcinoma cells, A549. Cell viability of bare and L-arginine coated magnetite nanoparticles showed IC50 value of 31.2 g/mL proving the compatibility of nanocarriers when compared to others. Hence, L-arginine coated nanoparticles were used for loading the drug paclitaxel and the observed IC50 value (7.8 g/mL) shows its potent anti-proliferative effect against A549 lung cancer cell lines. Thus, it can be speculated that the drug paclitaxel loaded L-arginine coated nanoparticles could be used as an effective drug carrier for the destruction of cancer cells.

  3. Texture Analysis and Synthesis of Malignant and Benign Mediastinal Lymph Nodes in Patients with Lung Cancer on Computed Tomography.

    Science.gov (United States)

    Pham, Tuan D; Watanabe, Yuzuru; Higuchi, Mitsunori; Suzuki, Hiroyuki

    2017-02-24

    Texture analysis of computed tomography (CT) imaging has been found useful to distinguish subtle differences, which are in- visible to human eyes, between malignant and benign tissues in cancer patients. This study implemented two complementary methods of texture analysis, known as the gray-level co-occurrence matrix (GLCM) and the experimental semivariogram (SV) with an aim to improve the predictive value of evaluating mediastinal lymph nodes in lung cancer. The GLCM was explored with the use of a rich set of its derived features, whereas the SV feature was extracted on real and synthesized CT samples of benign and malignant lymph nodes. A distinct advantage of the computer methodology presented herein is the alleviation of the need for an automated precise segmentation of the lymph nodes. Using the logistic regression model, a sensitivity of 75%, specificity of 90%, and area under curve of 0.89 were obtained in the test population. A tenfold cross-validation of 70% accuracy of classifying between benign and malignant lymph nodes was obtained using the support vector machines as a pattern classifier. These results are higher than those recently reported in literature with similar studies.

  4. Dynamics of ellipsoidal tracers in swimming algal suspensions

    Science.gov (United States)

    Yang, Ou; Peng, Yi; Liu, Zhengyang; Tang, Chao; Xu, Xinliang; Cheng, Xiang

    2016-10-01

    Enhanced diffusion of passive tracers immersed in active fluids is a universal feature of active fluids and has been extensively studied in recent years. Similar to microrheology for equilibrium complex fluids, the unusual enhanced particle dynamics reveal intrinsic properties of active fluids. Nevertheless, previous studies have shown that the translational dynamics of spherical tracers are qualitatively similar, independent of whether active particles are pushers or pullers—the two fundamental classes of active fluids. Is it possible to distinguish pushers from pullers by simply imaging the dynamics of passive tracers? Here, we investigated the diffusion of isolated ellipsoids in algal C. reinhardtii suspensions—a model for puller-type active fluids. In combination with our previous results on pusher-type E. coli suspensions [Peng et al., Phys. Rev. Lett. 116, 068303 (2016), 10.1103/PhysRevLett.116.068303], we showed that the dynamics of asymmetric tracers show a profound difference in pushers and pullers due to their rotational degree of freedom. Although the laboratory-frame translation and rotation of ellipsoids are enhanced in both pushers and pullers, similar to spherical tracers, the anisotropic diffusion in the body frame of ellipsoids shows opposite trends in the two classes of active fluids. An ellipsoid diffuses fastest along its major axis when immersed in pullers, whereas it diffuses slowest along the major axis in pushers. This striking difference can be qualitatively explained using a simple hydrodynamic model. In addition, our study on algal suspensions reveals that the influence of the near-field advection of algal swimming flows on the translation and rotation of ellipsoids shows different ranges and strengths. Our work provides not only new insights into universal organizing principles of active fluids, but also a convenient tool for detecting the class of active particles.

  5. Numerical simulations of the spread of floating passive tracer released at the Old Harry prospect

    Science.gov (United States)

    Bourgault, Daniel; Cyr, Frédéric; Dumont, Dany; Carter, Angela

    2014-05-01

    The Gulf of St Lawrence is under immediate pressure for oil and gas exploration, particularly at the Old Harry prospect. A synthesis of the regulatory process that has taken place over the last few years indicates that important societal decisions soon to be made by various ministries and environmental groups are going to be based on numerous disagreements between the private sector and government agencies. The review also shows that the regulatory process has taken place with a complete lack of independent oceanographic research. Yet, the Gulf of St Lawrence is a complex environment that has never been specifically studied for oil and gas exploitation. Motivated by this knowledge gap, preliminary numerical experiments are carried out where the spreading of a passive floating tracer released at Old Harry is examined. Results indicate that the tracer released at Old Harry may follow preferentially two main paths. The first path is northward along the French Shore of Newfoundland, and the second path is along the main axis of the Laurentian Channel. The most probable coastlines to be touched by water flowing through Old Harry are Cape Breton and the southern portion of the French Shore, especially Cape Anguille and the Port au Port Peninsula. The Magdalen Islands are less susceptible to being affected than those regions but the probability is not negligible. These preliminary results provide guidance for future more in-depth and complete multidisciplinary studies from which informed decision-making scenarios could eventually be made regarding the exploration and development of oil and gas at the Old Harry prospect in particular and, more generally, in the Gulf of St Lawrence.

  6. Synthesis and anti-cancer activity evaluation of novel prenylated and geranylated chalcone natural products and their analogs.

    Science.gov (United States)

    Wang, Hao-Meng; Zhang, Li; Liu, Jiang; Yang, Zhao-Liang; Zhao, Hong-Ye; Yang, Yao; Shen, Di; Lu, Kui; Fan, Zhen-Chuan; Yao, Qing-Wei; Zhang, Yong-Min; Teng, Yu-Ou; Peng, Yu

    2015-03-06

    Four natural chalcones bearing prenyl or geranyl groups, i.e., bavachalcone (1a), xanthoangelol (1b), isobavachalcone (1c), and isoxanthoangelol (1d) were synthesized by using a regio-selective iodination and the Suzuki coupling reaction as key steps. The first total synthesis of isoxanthoangelol (1d) was achieved in 36% overall yield. A series of diprenylated and digeranylated chalcone analogs were also synthesized by alkylation, regio-selective iodination, aldol condensation, Suzuki coupling and [1,3]-sigmatropic rearrangement. The structures of the 11 new derivatives were confirmed by (1)H NMR, (13)C NMR and HRMS. The anticancer activity of these new chalcone derivatives against human tumor cell line K562 were evaluated by MTT assay in vitro. SAR studies suggested that the 5'-prenylation/geranylation of the chalcones significantly enhance their cytotoxic activity. Among them, Bavachalcone (1a) displayed the most potent cytotoxic activity against K562 with IC50 value of 2.7 μM. The morphology changes and annexin-V/PI staining studies suggested that those chalcone derivatives inhibited the proliferation of K562 cells by inducing apoptosis.

  7. Solid phase synthesis of tariquidar-related modulators of ABC transporters preferring breast cancer resistance protein (ABCG2).

    Science.gov (United States)

    Puentes, Cristian Ochoa; Höcherl, Peter; Kühnle, Matthias; Bauer, Stefanie; Bürger, Kira; Bernhardt, Günther; Buschauer, Armin; König, Burkhard

    2011-06-15

    Aiming at structural optimization of potent and selective ABCG2 inhibitors, such as UR-ME22-1, from our laboratory, an efficient solid phase synthesis was developed to get convenient access to this class of compounds. 7-Carboxyisatoic anhydride was attached to Wang resin to give resin bound 2-aminoterephthalic acid. Acylation with quinoline-2- or -6-carbonyl chlorides, coupling with tetrahydroisoquinolinylethylphenylamine derivatives, cleavage of the carboxylic acids from solid support and treatment with trimethylsilydiazomethane gave the corresponding methyl esters. Among these esters highly potent and selective ABCG2 modulators were identified (inhibition of ABCB1 and ABCG2 determined in the calcein-AM and the Hoechst 33342 microplate assay, respectively). Interestingly, compounds bearing triethyleneglycol ether groups at the tetrahydroisoquinoline moiety (UR-COP77, UR-COP78) were comparable to UR-ME22-1 in potency but considerably more efficient (max inhibition 83% and 88% vs 60%, rel. to fumitremorgin c, 100%) These results support the hypothesis that solubility of the new ABCG2 modulators and of the reference compounds tariquidar and elacridar in aqueous media is the efficacy-limiting factor.

  8. Quantification of lung cancer risk after low radon exposure and low exposure rate: synthesis from epidemiological and experimental data

    Energy Technology Data Exchange (ETDEWEB)

    Timarche, M

    2004-03-15

    Radon is a radioactive gas produced during the decay of uranium 238 that is present in soil. It was classified as a human lung carcinogen in 1988, based on evidence both from animal studies and from human studies of miners with high levels of radon exposure. Radon is present everywhere; therefore the quantification of the risk associated with exposure to it is a key public health issue. The project aimed to analyse the risk associated with radon inhalation at low doses and at low rates of exposure. It involved researchers from three different fields: epidemiology, animal experiments and mechanistic modelling and provided a unique opportunity to study the influence of dose rate, mainly in the range of low daily exposures over long periods, by analysing in parallel results from both animal and epidemiological studies. The project comprised 6 work packages (W.P.). Firstly, the partners involved in epidemiology and animal experiments worked on the validation and the analysis of the data. Secondly, the data from W.P.1 and W.P.4 were transferred to the partners involved in W.P.5 for the application of mechanistic models. In the final step a synthesis of the results was prepared. (N.C)

  9. Design and synthesis of novel 1,2,3-triazole derivatives of coronopilin as anti-cancer compounds.

    Science.gov (United States)

    Khazir, Jabeena; Hyder, Irfan; Gayatri, J Laxmi; Prasad Yandrati, Leela; Nalla, Naresh; Chasoo, Gousia; Mahajan, Ajay; Saxena, A K; Alam, M S; Qazi, G N; Sampath Kumar, Halmuthur M

    2014-07-23

    A series of 1,2,3-triazole coronopilin congeners have been designed and synthesized by employing click chemistry approach starting from parthenin and evaluated for their cytotoxicity against a panel of six human cancer cell lines (PC-3, THP-1, HCT-15, HeLa, A-549 and MCF-7). While many compounds exhibited significant anticancer activity, compound 3a, was found to be the most promising analogue in this series with IC50 values of 3.1 μM on PC-3 cell line. Flow-cytometric studies showed that 1,2,3-triazole derivative-3a induce dose dependent apoptosis in the sub G1 phase. This lead molecule-3a was further studied for NF-κB (p65) transcription factor inhibitory activity using Elisa and western blotting analysis which confirmed concentration dependent inhibitory activity against NF-κB, p65 with 80% inhibition in 24 h at 100 μM.

  10. Benzothiepin-derived molecular scaffolds for estrogen receptor modulators: synthesis and antagonistic effects in breast cancer cells.

    Science.gov (United States)

    Meegan, Mary J; Barrett, Irene; Zimmermann, Jochen; Knox, Andrew J S; Zisterer, Daniela M; Lloyd, David G

    2007-10-01

    A series of novel benzothiepin-derived compounds are described as potent selective modulators of the human estrogen receptor (SERMs). The objective of the study is to evaluate the antiproliferative effects of the compounds on human MCF-7 breast tumor cells. These heterocyclic compounds contain the traditional triarylethylene arrangement exemplified by tamoxifen, conformationally restrained through the incorporation of the benzothiepin ring system. The compounds demonstrated potency at nanomolar concentrations in antiproliferative assays against an MCF-7 human breast cancer cell line with low cytotoxicity. The compounds exhibited low nanomolar binding affinity for the estrogen receptor (ER) with some specificity for ERbeta, and also demonstrate potent antiestrogenic properties in the human uterine Ishikawa cell line. The effect of a number of functional group substitutions on the ER binding properties of the benzothiepin molecular scaffold is explored through a brief computational structure-activity relationship investigation with molecular simulation.

  11. Synthesis, characterization, plasmid cleavage and cytotoxicity of cancer cells by a copper(II) complex of anthracenyl-terpyridine.

    Science.gov (United States)

    Kumar, Amit; Chinta, Jugun Prakash; Ajay, Amrendra Kumar; Bhat, Manoj Kumar; Rao, Chebrolu P

    2011-11-01

    Metallo-organic compounds are interesting to study for their antitumor activity and related applications. This paper deals with the syntheses, characterization, structure determination of a copper complex of anthracenyl terpyridine (1) and its plasmid cleavage and cytotoxicity towards different cancer cell lines. The complex binds CT-DNA through partial intercalation mode. The plasmid cleavage studies carried out using pBR322 and pUC18 resulted in the formation of all the three forms of the plasmid DNA. Plasmid cleavage studies carried out with a non-redoxable Zn(2+) complex (2) supported the role of the redox activity of copper in 1. The complex 1 showed remarkable antiproliferative activity against cancer cell lines, viz., cervical (HeLa, SiHa, CaSki), breast (MCF-7), liver (HepG2) and lung (H1299). A considerable lowering was observed in the IC(50) values of HPV-infected (viz., HeLa, SiHa, CaSki) vs. non-HPV-infected cell lines (MCF-7, HepG2, H1299). Antiproliferative activity of 1 was found to be much higher than the carboplatin when treated with the same cell lines. Incubation of the cells with 1 results in granular structures only with the HPV-infected cells and not with others as studied by phase contrast and fluorescence microscopy. The lower IC(50) value observed in case of 1 with HPV-infected cell lines may be correlated with the involvement of HPV oncoprotein. The role of HPV has been further augmented by transfecting the MCF-7 cells (originally not possessing HPV copy) with e6 oncoprotein cDNA. To our knowledge this is the first copper complex that causes cell death by interacting with HPV oncoprotein followed by exhibition of remarkable antiproliferative activity.

  12. Synthesis of 2'-deoxy-2'-[.sup.18F]fluoro-5-methyl-1-B-D-arabinofuranosyluracil (.sup.18F-FMAU)

    Energy Technology Data Exchange (ETDEWEB)

    Li, Zibo; Cai, Hancheng; Conti, Peter S

    2014-12-16

    The present invention relates to methods of synthesizing .sup.18F-FMAU. In particular, .sup.18F-FMAU is synthesized using one-pot reaction conditions in the presence of Friedel-Crafts catalysts. The one-pot reaction conditions are incorporated into a fully automated cGMP-compliant radiosynthesis module, which results in a reduction in synthesis time and simplifies reaction conditions. The one-pot reaction conditions are also suitable for the production of 5-substituted thymidine or cytidine analogs. The products from the one-pot reaction (e.g. the labeled thymidine or cytidine analogs) can be used as probes for imaging tumor proliferative activity. More specifically, these [.sup.18F]-labeled thymidine or cytidine analogs can be used as a PET tracer for certain medical conditions, including, but not limited to, cancer disease, autoimmunity inflammation, and bone marrow transplant.

  13. Targeted polyethylene glycol gold nanoparticles for the treatment of pancreatic cancer: from synthesis to proof-of-concept in vitro studies

    Directory of Open Access Journals (Sweden)

    Spadavecchia J

    2016-02-01

    Full Text Available Jolanda Spadavecchia,1,2,* Dania Movia,3,* Caroline Moore,3,4 Ciaran Manus Maguire,3,4 Hanane Moustaoui,2 Sandra Casale,1 Yuri Volkov,3,4 Adriele Prina-Mello3,4 1Laboratoire de Réactivité de Surface, Sorbonne Universités, UPMC Univ Paris VI, Paris, 2Centre National de la recherche française, UMR 7244, CSPBAT, Laboratory of Chemistry, Structures, and Properties of Biomaterials and Therapeutic Agents, Université Paris 13, Sorbonne Paris Cité, Bobigny, France; 3AMBER Centre, CRANN Institute, 4Department of Clinical Medicine, School of Medicine, Trinity College, Dublin, Ireland *These authors contributed equally to this work Abstract: The main objective of this study was to optimize and characterize a drug delivery carrier for doxorubicin, intended to be intravenously administered, capable of improving the therapeutic index of the chemotherapeutic agent itself, and aimed at the treatment of pancreatic cancer. In light of this goal, we report a robust one-step method for the synthesis of dicarboxylic acid-terminated polyethylene glycol (PEG-gold nanoparticles (AuNPs and doxorubicin-loaded PEG-AuNPs, and their further antibody targeting (anti-Kv11.1 polyclonal antibody [pAb]. In in vitro proof-of-concept studies, we evaluated the influence of the nanocarrier and of the active targeting functionality on the anti-tumor efficacy of doxorubicin, with respect to its half-maximal effective concentration (EC50 and drug-triggered changes in the cell cycle. Our results demonstrated that the therapeutic efficacy of doxorubicin was positively influenced not only by the active targeting exploited through anti-Kv11.1-pAb but also by the drug coupling with a nanometer-sized delivery system, which indeed resulted in a 30-fold decrease of doxorubicin EC50, cell cycle blockage, and drug localization in the cell nuclei. The cell internalization pathway was strongly influenced by the active targeting of the Kv11.1 subunit of the human Ether-à-go-go related gene

  14. Assessment of Halon-1301 as a groundwater age tracer

    Directory of Open Access Journals (Sweden)

    M. Beyer

    2015-01-01

    Full Text Available Groundwater dating is an important tool to assess groundwater resources in regards to their dynamics, i.e. direction and time scale of groundwater flow and recharge, to assess contamination risks and manage remediation. To infer groundwater age information, a combination of different environmental tracers, such as tritium and SF6, are commonly used. However, ambiguous age interpretations are often faced, due to a limited set of available tracers and their individual restricted application ranges. For more robust groundwater dating multiple tracers need to be applied complementarily and it is vital that additional, groundwater age tracers are found to ensure robust groundwater dating in future. We recently suggested that Halon-1301, a water soluble and entirely anthropogenic gaseous substance, may be a promising candidate, but its behaviour in water and suitability as a groundwater age tracer had not yet been assessed in detail. In this study, we determine Halon-1301 and infer age information in 17 New Zealand groundwaters and various modern (river water samples. The samples are simultaneously analysed for Halon-1301 and SF6, which allows identification of issues such as contamination of the water with modern air during sampling. Water at all analysed groundwater sites have also been previously dated with tritium, CFC-12, CFC-11 and SF6, and exhibit mean residence times ranging from modern (close to 0 years to over 100 years. The investigated groundwater ranged from oxic to highly anoxic, and some showed evidence of CFC contamination or degradation. This allowed us to make a first attempt of assessing the conservativeness of Halon-1301 in water, in terms of presence of local sources and its sensitivity towards degradation etc., which could affect the suitability of Halon-1301 as groundwater age tracer. Overall we found Halon-1301 reliably inferred the mean residence time of groundwater recharged between 1980 and 2014. Where direct age comparison

  15. Synthesis and biodistribution of novel magnetic-poly(HEMA-APH) nanopolymer radiolabeled with iodine-131 and investigation its fate in vivo for cancer therapy

    Energy Technology Data Exchange (ETDEWEB)

    Avc Latin-Small-Letter-Dotless-I bas Latin-Small-Letter-Dotless-I , Ugur, E-mail: uguravcibasi@yahoo.com [Celal Bayar University, Department of Chemistry, Faculty of Arts and Science (Turkey); Avc Latin-Small-Letter-Dotless-I bas Latin-Small-Letter-Dotless-I , Nesibe [Ege University, Ege Higher Vocational School (Turkey); Akal Latin-Small-Letter-Dotless-I n, Hilmi Arkut; Ediz, Melis; Demiroglu, Hasan [Celal Bayar University, Department of Chemistry, Faculty of Arts and Science (Turkey); Guemueser, Fikriye Guel [Celal Bayar University, Department of Nuclear Medicine, Faculty of Medicine (Turkey); Oezcal Latin-Small-Letter-Dotless-I skan, Emir; Tuerkcan, Ceren [Ege University, Department of Biochemistry, Faculty of Science (Turkey); Uygun, Deniz Aktas [Adnan Menderes University, Department of Chemistry, Faculty of Arts and Science (Turkey); Akgoel, Sinan [Ege University, Department of Biochemistry, Faculty of Science (Turkey)

    2013-10-15

    Herein, we investigated the biological uptake, distribution, and radiopharmaceutical potential of a novel molecule based on 2-hydroxyethyl methacrylate (HEMA) and anilinephtalein (APH) in the metabolism of Albino Wistar rats. In order to achieve this, we synthesized APH using organic synthesis methods and copolymerized APH with HEMA using a common polymerization method, surfactant-free emulsion polymerization. In the presence of Fe{sub 3}O{sub 4} particles, we obtained a new generation magnetic-nano-scale polymer, magnetic-poly(HEMA-APH). This new molecule was chemically identified and approved by several characterization methods using Fourier transform infrared spectroscopy, scanning electron microscope, energy dispersive X-ray spectroscopy, electron spin resonance, atomic force microscope, and Zeta particle-size analysis. To evaluate the biological activity in live metabolism and anti-cancer potential of mag-poly(HEMA-APH), molecule was radioiodinated by a widely used labeling technique, iodogen method, with a gamma diffuser radionuclide, {sup 131}I. Thin-layer radiochromatography experiments demonstrated that {sup 131}I binded to nanopolymer with the labeling yield of 90 %. Lipophilicity and stability experiments were conducted to determine the condition of cold and labeled mag-poly(HEMA-APH) in rat blood and lipid medium. Results demonstrated that radioiodinated molecule stayed as an intact complex in rat metabolism for 24 h and experimental lipophilicity was determined as 0.12 {+-} 0.02. In vivo results obtained by imaging and biological distribution experiments indicated that mag-poly(HEMA-APH) labeled with {sup 131}I [{sup 131}I-mag-poly(HEMA-APH)] highly incorporated into tissues of the uterus, the ovarian, the prostate, and the lungs in rat metabolism. Based on these results, it may be evaluated that novel mag-poly(HEMA-APH) molecule labeled with {sup 131}I is a compound which has a significant potential for being used as an anti-cancer agent. Certain

  16. Synthesis, properties, and in vivo evaluation of sustained release albumin-mitoxantrone microsphere formulations for nonsystemic treatment of breast cancer and other high mortality cancers

    Science.gov (United States)

    Hadba, Ahmad Robert

    Methods for preparing mitoxantrone (MXN)-loaded albumin microspheres for the treatment of breast cancer were developed. The effect of processing conditions on the particle size of unloaded and MXN-loaded microspheres was evaluated using multivariate analyses. The data suggested that the particle size of unloaded microspheres increased as protein concentration increased or the steric stabilizer concentration decreased. In addition, synergy between these two variables was observed. In situ-loading of MXN achieved loading efficiencies in excess of 80%. Comparable efficiencies were achieved with postsynthesis loading when the microsphere were prepared from albumin-poly(glutamic acid) blends. In vitro release of MXN in phosphate buffered saline under infinite sink conditions showed that the total amount of drug released increased as the glutaraldehyde concentration decreased. This trend was reversed when the microspheres were incubated in plasma. Nanoparticles were also prepared using ethanol desolvation. These particles were dispersible in saline and easily modified with amino acids. In addition, particle size could be varied by use of different non-ionic surfactants in the preparation. The effect of intratumoral (IT) versus intravenous (IV) drug administration on tumor response and systemic toxicity was investigated in vivo using the 16/C murine mammary adenocarcinoma tumor model. The data suggested that IT-treated animals had significantly smaller tumors and lower weight loss when compared to IV-treated animals. Furthermore, the addition of surgery to the chemotherapy further improved the survival of the animals. Pilot studies using MXN-albumin microspheres suggested that microspheres could be safely administered IT in doses up to 48 mg/kg. However, there was no evidence that this higher dose resulted in improved long term survival when compared to the 32 mg/kg dose. The maximum tolerated dose of MAN given IT was approximately 12 mg/kg. The animal studies suggested

  17. Synthesis of novel {sup 68}Ga-labeled amino acid derivatives for positron emission tomography of cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Shetty, Dinesh [Department of Nuclear Medicine, Institute of Radiation Medicine, Seoul National University College of Medicine, Seoul 110-744 (Korea, Republic of); Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-744 (Korea, Republic of); Department of Radiation Applied Life Science, Seoul National University College of Medicine, Seoul 110-744 (Korea, Republic of); Jeong, Jae Min, E-mail: jmjng@snu.ac.k [Department of Nuclear Medicine, Institute of Radiation Medicine, Seoul National University College of Medicine, Seoul 110-744 (Korea, Republic of); Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-744 (Korea, Republic of); Department of Radiation Applied Life Science, Seoul National University College of Medicine, Seoul 110-744 (Korea, Republic of); Ju, Chang Hwan [Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-744 (Korea, Republic of); Department of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul (Korea, Republic of); Lee, Yun-Sang [Department of Nuclear Medicine, Institute of Radiation Medicine, Seoul National University College of Medicine, Seoul 110-744 (Korea, Republic of); Department of Radiation Applied Life Science, Seoul National University College of Medicine, Seoul 110-744 (Korea, Republic of); Jeong, Seo Young [Department of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul (Korea, Republic of); Choi, Jae Yeon; Yang, Bo Yeun [Department of Nuclear Medicine, Institute of Radiation Medicine, Seoul National University College of Medicine, Seoul 110-744 (Korea, Republic of); Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-744 (Korea, Republic of); Department of Radiation Applied Life Science, Seoul National University College of Medicine, Seoul 110-744 (Korea, Republic of)

    2010-11-15

    Objectives: We developed amino acid derivatives of 1,4,7,10-tetraazacyclododecane-1,7-diacetic acid (DO2A) and 1,4,7,10-tetraazacyclododecane-1,4,7,-triacetic acid (DO3A) that can be labeled with {sup 68}Ga, and we investigated their basic biological properties. Materials and methods: Alanine derivatives of DO2A and DO3A were synthesized by regiospecific nucleophilic attack of DO2tBu and DO3tBu on the {beta}-position of Boc-L-serine-{beta}-lactone, followed by acid hydrolysis. Also, homoalanine derivatives were synthesized by reacting with the protected bromo derivative of homoalanine, which was synthesized from N-Cbz-L-homoserine lactone. Further catalytic reduction and acid cleavage of protected groups resulted in the required products. All derivatives were labeled with {sup 68}Ga. Cell uptake assays were carried out in Hep3B (human hepatoma) and U87MG (human glioma) cell lines at 37{sup o}C. Positron emission tomography (PET) imaging studies were performed using balb/c mice xenografted with CT-26 (mouse colon cancer). Results: All compounds were labeled with >97% efficiency. According to in vitro studies, the labeled amino acid derivatives showed significantly greater uptakes than the control ({sup 68}Ga 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) in cancer cells. Small animal PET images for labeled compounds showed high tumor uptake, as well as kidney and bladder uptakes, at 30 min postinjection. {sup 68}Ga-DO3A-homoalanine showed the highest standardized uptake value ratio (3.9{+-}0.3), followed by {sup 68}Ga-DO2A-alanine (3.1{+-}0.2), {sup 68}Ga-DO3A-alanine (2.8{+-}0.2) and {sup 68}Ga-DO2A-homoalanine (2.3{+-}0.2). Conclusion: These derivatives were found to have high labeling efficiencies, high stabilities, high tumor cell uptakes, high tumor/nontumor xenograft uptakes and low nonspecific uptake in normal organs, except for the kidneys. However, the uptake mechanism of these derivatives remains unclear, and uptake via specific amino acid

  18. Thermally cross-linked superparamagnetic iron oxide nanoparticles: synthesis and application as a dual imaging probe for cancer in vivo.

    Science.gov (United States)

    Lee, Haerim; Yu, Mi Kyung; Park, Sangjin; Moon, Sungmin; Min, Jung Jun; Jeong, Yong Yeon; Kang, Hae-Won; Jon, Sangyong

    2007-10-24

    We report the fabrication and characterization of thermally cross-linked superparamagnetic iron oxide nanoparticles (TCL-SPION) and their application to the dual imaging of cancer in vivo. Unlike dextran-coated cross-linked iron oxide nanoparticles, which are prepared by a chemical cross-linking method, TCL-SPION are prepared by a simple, thermal cross-linking method using a Si-OH-containing copolymer. The copolymer, poly(3-(trimethoxysilyl)propyl methacrylate-r-PEG methyl ether methacrylate-r-N-acryloxysuccinimide), was synthesized by radical polymerization and used as a coating material for as-synthesized magnetite (Fe3O4) SPION. The polymer-coated SPION was further heated at 80 degrees C to induce cross-linking between the -Si(OH)3 groups in the polymer chains, which finally generated TCL-SPION bearing a carboxyl group as a surface functional group. The particle size, surface charge, presence of polymer-coating layers, and the extent of thermal cross-linking were characterized and confirmed by various measurements, including dynamic light scattering, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy. The carboxyl TCL-SPION was converted to amine-modified TCL-SPION and then finally to Cy5.5 dye-conjugated TCL-SPION for use in dual (magnetic resonance/optical) in vivo cancer imaging. When the Cy5.5 TCL-SPION was administered to Lewis lung carcinoma tumor allograft mice by intravenous injection, the tumor was unambiguously detected in T2-weighted magnetic resonance images as a 68% signal drop as well as in optical fluorescence images within 4 h, indicating a high level of accumulation of the nanomagnets within the tumor site. In addition, ex vivo fluorescence images of the harvested tumor and other major organs further confirmed the highest accumulation of the Cy5.5 TCL-SPION within the tumor. It is noteworthy that, despite the fact that TCL-SPION does not bear any targeting ligands on its surface, it was highly effective for tumor

  19. Synthesis and characterization of multifunctional hybrid-polymeric nanoparticles for drug delivery and multimodal imaging of cancer

    Directory of Open Access Journals (Sweden)

    Tng DJH

    2015-09-01

    Full Text Available Danny Jian Hang Tng,1,* Peiyi Song,1,* Guimiao Lin,2,3,* Alana Mauluidy Soehartono,1 Guang Yang,1 Chengbin Yang,1 Feng Yin,1 Cher Heng Tan,4 Ken-Tye Yong1 1School of Electrical and Electronic Engineering, Nanyang Technological University, Singapore; 2The Engineering Lab of Synthetic Biology, 3Research Institute of Uropoiesis and Reproduction, School of Medicine, Shenzhen University, Shenzhen, People’s Republic of China; 4Department of Diagnostic Radiology, Tan Tock Seng Hospital, Singapore *These authors contributed equally to this work Abstract: In this study, multifunctional hybrid-polymeric nanoparticles were prepared for the treatment of cultured multicellular tumor spheroids (MCTS of the PANC-1 and MIA PaCa-2 pancreatic carcinoma cell lines. To synthesize the hybrid-polymeric nanoparticles, the poly lactic-co-glycolic acid core of the particles was loaded with Rhodamine 6G dye and the chemotherapeutic agent, Paclitaxel, was incorporated into the outer phospholipid layer. The surface of the nanoparticles was coated with gadolinium chelates for magnetic resonance imaging applications. This engineered nanoparticle formulation was found to be suitable for use in guided imaging therapy. Specifically, we investigated the size-dependent therapeutic response and the uptake of nanoparticles that were 65 nm, 85 nm, and 110 nm in size in the MCTS of the two pancreatic cancer cell lines used. After 24 hours of treatment, the MCTS of both PANC-1 and MIA PaCa-2 cell lines showed an average increase in the uptake of 18.4% for both 65 nm and 85 nm nanoparticles and 24.8% for 110 nm nanoparticles. Furthermore, the studies on therapeutic effects showed that particle size had a slight influence on the overall effectiveness of the formulation. In the MCTS of the MIA PaCa-2 cell line, 65 nm nanoparticles were found to produce the greatest therapeutic effect, whereas 12.8% of cells were apoptotic of which 11.4% of cells were apoptotic for 85

  20. Microbial synthesis of gold nanoparticles using the fungus Penicillium brevicompactum and their cytotoxic effects against mouse mayo blast cancer C 2 C 12 cells.

    Science.gov (United States)

    Mishra, Amrita; Tripathy, Suraj Kumar; Wahab, Rizwan; Jeong, Song-Hoon; Hwang, Inho; Yang, You-Bing; Kim, Young-Soon; Shin, Hyung-Shik; Yun, Soon-Il

    2011-11-01

    Microorganisms, their cell filtrates, and live biomass have been utilized for synthesizing various gold nanoparticles. The shape, size, stability as well as the purity of the bio synthesized nanoparticles become very essential for application purpose. In the present study, gold nanoparticles have been synthesized from the supernatant, live cell filtrate, and biomass of the fungus Penicillium brevicompactum. The fungus has been grown in potato dextrose broth which is also found to synthesize gold nanoparticles. The size of the particles has been investigated by Bio-TEM before purification, following purification and after storing the particles for 3 months under refrigerated condition. Different characterization techniques like X-ray diffraction, Fourier transform infrared spectroscopy, and UV-visible spectroscopy have been used for analysis of the particles. The effect of reaction parameters such as pH and concentration of gold salt have also been monitored to optimize the morphology and dispersity of the synthesized gold nanoparticles. A pH range of 5 to 8 has favored the synthesis process whereas increasing concentration of gold salt (beyond 2 mM) has resulted in the formation of bigger sized and aggregated nanoparticles. Additionally, the cytotoxic nature of prepared nanoparticles has been analyzed using mouse mayo blast cancer C(2)C(12) cells at different time intervals (24, 48, and 72 h) of incubation period. The cells are cultivated in Dulbecco's modified Eagle's medium supplemented with fetal bovine serum with antibiotics (streptopenicillin) at 37°C in a 5% humidified environment of CO(2). The medium has been replenished every other day, and the cells are subcultured after reaching the confluence. The viability of the cells is analyzed with 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide method.

  1. A monitoring system of radioactive tracers in hydroponic solution for research on plant physiology

    Energy Technology Data Exchange (ETDEWEB)

    Suzui, N.; Kawachi, N.; Ishioka, N.; Fujimaki, S. [Quantum Beam Science Directorate, Japan Atomic Energy Agency, Takasaki, Gunma 370-1292 (Japan); Yamaguchi, M. [Takasaki Advanced Radiation Research Institute, Atomic Energy Agency, Takasaki, Gunma 370-1292 (Japan)

    2009-07-01

    The mechanism of nutrient uptake in plants has received considerable attention in the field of plant science. Here we describe the development of a new monitoring system of radioactive tracers in hydroponic solution, which enables the noninvasive measurement of radioactive tracer uptake by an intact plant. In addition, we incorporated a weighing instrument into this system in order to simultaneously monitor water uptake by the same plant. For an evaluation of this monitoring system, we conducted a tracer experiment with a rice plant and a positron-emitting radioactive tracer, and successfully obtained continuous data for the amounts of radioactive tracer and water taken up by the intact plant over 36 h. (authors)

  2. Synthesis and characterization of smart N-isopropylacrylamide-based magnetic nanocomposites containing doxorubicin anti-cancer drug.

    Science.gov (United States)

    Motaali, Soheila; Pashaeiasl, Maryam; Akbarzadeh, Abolfazl; Davaran, Soodabeh

    2017-05-01

    In the present study, magnetic and thermo/pH-sensitive (multiresponsive) nanocomposites based on N-isopropylacrylamide (NIPAAM) were synthesized and characterized. Nanocomposites were synthesized by free radical emulsion polymerization of NIPAAM as thermosensitive monomer and N,N-dimethyl-aminoethyl methacrylate (DMAEMA) as pH-sensitive monomer in the presence of methylene-bis-acrylamide as cross-linking agent. Doxorubicin, an anti-cancer drug, was loaded into these nanocomposites via equilibrium swelling method. Thermo/pH-sensitive cross-linked poly (NIPAAM-DMAEMA)-Fe3O4 nanocomposites were characterized by Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), and vibrating sample magnetometer (VSM). The volume of the loaded drug and drug release amount was determined by UV measurements. The results showed that this thermo/pH-sensitive magnetic nanocomposite has a high drug-loading efficiency. Doxorubicin was released at 40 °C and pH 5.8 more than the 37 °C and pH 7.4.

  3. Synthesis, docking and ADMET studies of novel chalcone triazoles for anti-cancer and anti-diabetic activity.

    Science.gov (United States)

    Chinthala, Yakaiah; Thakur, Sneha; Tirunagari, Shalini; Chinde, Srinivas; Domatti, Anand Kumar; Arigari, Niranjana Kumar; K V N S, Srinivas; Alam, Sarfaraz; Jonnala, Kotesh Kumar; Khan, Feroz; Tiwari, Ashok; Grover, Paramjit

    2015-03-26

    A series of novel chalcone-triazole derivatives were synthesized and screened for in vitro anticancer activity on the human cancer cell lines IMR32 (neuroblastoma), HepG2 (hepatoma) and MCF-7 (breast adenocarcinoma), DU-145 (prostate carcinoma), and A549 (lung adenocarcinoma). Among the tested compounds, 4r showed the most promising anticancer activity in all the cell lines whereas, compounds 4c (IC50 65.86 μM), 4e (IC50 66.28 μM), 4o (IC50 35.81 μM), 4q (IC50 50.82 μM) and 4s (IC50 48.63 μM) showed better activity than the standard doxorubicin (IC50 69.33 μM) in A549 cell line alone. Rat intestinal α-glucosidase inhibitory activity of the synthesized derivatives showed 4m (IC50 67.77 μM), 4p (IC50 74.94 in μM) and 4s (IC50 102.10 μM) as most active compared to others. The in silico docking of synthesized derivatives 4a-4t with DNA topoisomerase IIα revealed the LibDock score in the range of 71.2623-118.29 whereas, compounds 4h, 4m, 4p and 4s with docking target α-glucosidase were in the range of 100.372-107.784.

  4. Design, synthesis, and biological evaluation of resveratrol analogues as aromatase and quinone reductase 2 inhibitors for chemoprevention of cancer

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Bin; Hoshino, Juma; Jermihov, Katie; Marler, Laura; Pezzuto, John M.; Mesecar, Andrew D.; Cushman, Mark (Hawaii); (Purdue); (UIC)

    2012-07-11

    A series of new resveratrol analogues were designed and synthesized and their inhibitory activities against aromatase were evaluated. The crystal structure of human aromatase (PDB 3eqm) was used to rationalize the mechanism of action of the aromatase inhibitor 32 (IC{sub 50} 0.59 {mu}M) through docking, molecular mechanics energy minimization, and computer graphics molecular modeling, and the information was utilized to design several very potent inhibitors, including compounds 82 (IC{sub 50} 70 nM) and 84 (IC{sub 50} 36 nM). The aromatase inhibitory activities of these compounds are much more potent than that for the lead compound resveratrol, which has an IC{sub 50} of 80 {mu}M. In addition to aromatase inhibitory activity, compounds 32 and 44 also displayed potent QR2 inhibitory activity (IC{sub 50} 1.7 {mu}M and 0.27 {mu}M, respectively) and the high-resolution X-ray structures of QR2 in complex with these two compounds provide insight into their mechanism of QR2 inhibition. The aromatase and quinone reductase inhibitors resulting from these studies have potential value in the treatment and prevention of cancer.

  5. Synthesis and properties of novel water-soluble fullerene-glycine derivatives as new materials for cancer therapy.

    Science.gov (United States)

    Jiang, Guichang; Yin, Fen; Duan, Jihua; Li, Guangtao

    2015-01-01

    Novel water-soluble fullerene-glycine derivatives were synthesized by means of simple organic chemistry. They are completely soluble in water, yielding a clear brown solution. The products were characterized by fourier transform infrared (FTIR), ultraviolet-visible spectroscopy (UV-Vis), (1)H NMR, (13)C NMR, thermogravimetric analyses (TGA), and scanning electron microscopy (SEM). The assembly behavior of water-soluble fullerene-glycine derivatives was investigated by SEM. The results show that the fullerene-glycine derivatives create morphology that is sphere-like. The cytotoxicity to cancer cell lines of the fullerene-glycine derivatives was evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) and flow cytometry. The results show that fullerene-glycine derivatives exhibit mortality and apoptosis of the cells which increased with the increase of fullerene-glycine derivative concentration. The cytotoxicity mechanism of fullerene-glycine derivatives was investigated for the first time. Novel water-soluble fullerene-glycine derivatives were synthesized by means of simple organic chemistry. The products were characterized by FTIR, UV-Vis, (1)H NMR, (13)C NMR, TGA, and SEM. The bioactivities of fullerene-glycine derivative materials have been tested, and the results show that compared with the fullerene complex, the fullerene-glycine derivative materials exhibit mortality and apoptosis of the cells which increased with the increase of fullerene-glycine derivative concentration. SEM images showed the macrostructure of fullerene-glycine derivative materials was spheres.

  6. Small interfering RNA against transcription factor STAT6 leads to increased cholesterol synthesis in lung cancer cell lines.

    Directory of Open Access Journals (Sweden)

    Richa Dubey

    Full Text Available STAT6 transcription factor has become a potential molecule for therapeutic intervention because it regulates broad range of cellular processes in a large variety of cell types. Although some target genes and interacting partners of STAT6 have been identified, its exact mechanism of action needs to be elucidated. In this study, we sought to further characterize the molecular interactions, networks, and functions of STAT6 by profiling the mRNA expression of STAT6 silenced human lung cells (NCI-H460 using microarrays. Our analysis revealed 273 differentially expressed genes after STAT6 silencing. Analysis of the gene expression data with Ingenuity Pathway Analysis (IPA software revealed Gene expression, Cell death, Lipid metabolism as the functions associated with highest rated network. Cholesterol biosynthesis was among the most enriched pathways in IPA as well as in PANTHER analysis. These results have been validated by real-time PCR and cholesterol assay using scrambled siRNA as a negative control. Similar findings were also observed with human type II pulmonary alveolar epithelial cells, A549. In the present study we have, for the first time, shown the inverse relationship of STAT6 with the cholesterol biosynthesis in lung cancer cells. The present findings are potentially significant to advance the understanding and design of therapeutics for the pathological conditions where both STAT6 and cholesterol biosynthesis are implicated viz. asthma, atherosclerosis etc.

  7. ARAC results from phase II of the European tracer experiment

    Energy Technology Data Exchange (ETDEWEB)

    Pace, J.C.; Nasstrom, J.S.

    1997-07-01

    A comparison is provided of the results of calculations by the Atmospheric Release Advisory Capability (ARAC) during two phases of the European Tracer Experiment (ETEX). In phase I of ETEX, participants generated predictions in real time of the concentration of inert tracer gases released from a site in Western France. Each participating group based their predictions on the meteorological data they had available. In phase II, all participants were required to recalculate predictions based on the same meteorological data, which was generated and supplied by the European Centre for Medium- Range Weather Forecasts (ECMWF). ARAC used ECMWF data and also made additional changes to its model configuration,, with the result that ARAC`s accuracy during phase II was much better than for phase I. Experiments described in this paper examine the effect of each of these changes, and show that each change contributed to the improvement.

  8. A Galaxy-Halo Model for Multiple Cosmological Tracers

    CERN Document Server

    Bull, Philip

    2016-01-01

    The information extracted from large galaxy surveys with the likes of DES, DESI, Euclid, LSST, SKA, and WFIRST will be greatly enhanced if the resultant galaxy catalogues can be cross-correlated with one another. Predicting the nature of the information gain, and developing the tools to realise it, depends on establishing a consistent model of how the galaxies detected by each survey trace the same underlying matter distribution. Existing analytic methods, such as halo occupation distribution (HOD) modelling, are not well-suited for this task, and can suffer from ambiguities and tuning issues when applied to multiple tracers. We construct a simple alternative that provides a common model for the connection between galaxies and dark matter halos across a wide range of wavelengths (and thus tracer populations). This is based on a chain of parametrised statistical distributions that model the connection between (a) halo mass and bulk physical properties of galaxies, such as star-formation rate; and (b) those sam...

  9. In-situ fracture mapping using geotomography and brine tracers

    Energy Technology Data Exchange (ETDEWEB)

    Deadrick, F.J.; Ramirez, A.L.; Lytle, R.J.

    1981-01-01

    The Lawrence Livermore National Laboratory is currently assessing the capabilities of high resolution geophysical methods to characterize geologic sites for the disposal of high level nuclear waste. A successful experiment has recently been performed in which salt water tracers and high frequency electromagnetic waves were utilized to map rock mass fracture zones in-situ. Multiple cross-borehole EM transmissions were used to generate a tomographic image of the fractured rock region between two boreholes. The tomographs obtained correlate well with conventional wireline geophysical logs which can be used to infer the location of fractured zones in the rock mass. This indirect data suggests that the geotomography and brine tracer technique may have merit in mapping fractured zones between boreholes.

  10. A historical perspective on radioisotopic tracers in metabolism and biochemistry.

    Science.gov (United States)

    Lappin, Graham

    2015-01-01

    Radioisotopes are used routinely in the modern laboratory to trace and quantify a myriad of biochemical processes. The technique has a captivating history peppered with groundbreaking science and with more than its share of Nobel Prizes. The discovery of radioactivity at the end of the 19th century paved the way to understanding atomic structure and quickly led to the use of radioisotopes to trace the fate of molecules as they flowed through complex organic life. The 1940s saw the first radiotracer studies using homemade instrumentation and analytical techniques such as paper chromatography. This article follows the history of radioisotopic tracers from meager beginnings, through to the most recent applications. The author hopes that those researchers involved in radioisotopic tracer studies today will pause to remember the origins of the technique and those who pioneered this fascinating science.

  11. Artificial sweeteners as potential tracers of municipal landfill leachate.

    Science.gov (United States)

    Roy, James W; Van Stempvoort, Dale R; Bickerton, Greg

    2014-01-01

    Artificial sweeteners are gaining acceptance as tracers of human wastewater in the environment. The 3 artificial sweeteners analyzed in this study were detected in leachate or leachate-impacted groundwater at levels comparable to those of untreated wastewater at 14 of 15 municipal landfill sites tested, including several closed for >50 years. Saccharin was the dominant sweetener in old (pre-1990) landfills, while newer landfills were dominated by saccharin and acesulfame (introduced 2 decades ago; dominant in wastewater). Cyclamate was also detected, but less frequently. A case study at one site illustrates the use of artificial sweeteners to identify a landfill-impacted groundwater plume discharging to a stream. The study results suggest that artificial sweeteners can be useful tracers for current and legacy landfill contamination, with relative abundances of the sweeteners potentially providing diagnostic ability to distinguish different landfills or landfill cells, including crude age-dating, and to distinguish landfill and wastewater sources.

  12. FormTracer - A Mathematica Tracing Package Using FORM

    CERN Document Server

    Cyrol, Anton K; Strodthoff, Nils

    2016-01-01

    We present FormTracer, a high-performance, general purpose, easy-to-use Mathematica tracing package which uses FORM. It supports arbitrary space and spinor dimensions as well as an arbitrary number of simple compact Lie groups. While keeping the usability of the Mathematica interface, it relies on the efficiency of FORM. An additional performance gain is achieved by a decomposition algorithm that avoids redundant traces in the product tensors spaces. FormTracer supports a wide range of syntaxes which endows it with a high flexibility. Mathematica notebooks that automatically install the package and guide the user through performing standard traces in space-time, spinor and gauge-group spaces are provided.

  13. Application of enriched stable isotopes as tracers in biological systems

    DEFF Research Database (Denmark)

    Stürup, Stefan; Hansen, Helle Rüsz; Gammelgaard, Bente

    2008-01-01

    The application of enriched stable isotopes of minerals and trace elements as tracers in biological systems is a rapidly growing research field that benefits from the many new developments in inorganic mass spectrometric instrumentation, primarily within inductively coupled plasma mass spectrometry...... (ICP-MS) instrumentation, such as reaction/collision cell ICP-MS and multicollector ICP-MS with improved isotope ratio measurement and interference removal capabilities. Adaptation and refinement of radioisotope tracer experiment methodologies for enriched stable isotope experiments......, and the development of new methodologies coupled with more advanced compartmental and mathematical models for the distribution of elements in living organisms has enabled a broader use of enriched stable isotope experiments in the biological sciences. This review discusses the current and future uses of enriched...

  14. Tracer Methods for Characterizing Fracture Creation in Engineered Geothermal Systems

    Energy Technology Data Exchange (ETDEWEB)

    Rose, Peter [Energy & Geoscience Institute at the University of Utah, Salt Lake City, UT (United States); Harris, Joel [Univ. of Utah, Salt Lake City, UT (United States)

    2014-05-08

    The aim of this proposal is to develop, through novel high-temperature-tracing approaches, three technologies for characterizing fracture creation within Engineered Geothermal Systems (EGS). The objective of a first task is to identify, develop and demonstrate adsorbing tracers for characterizing interwell reservoir-rock surface areas and fracture spacing. The objective of a second task is to develop and demonstrate a methodology for measuring fracture surface areas adjacent to single wells. The objective of a third task is to design, fabricate and test an instrument that makes use of tracers for measuring fluid flow between newly created fractures and wellbores. In one method of deployment, it will be used to identify qualitatively which fractures were activated during a hydraulic stimulation experiment. In a second method of deployment, it will serve to measure quantitatively the rate of fluid flowing from one or more activated fracture during a production test following a hydraulic stimulation.

  15. Bromide as a tracer for studying water movement and nitrate displacement in soils: comparison with stable isotope tracers; Bromid als Tracer zur Untersuchung der Wasserbewegung und der Nitratverlagerung in Boeden: Vergleich mit stabilisotopen Tracern

    Energy Technology Data Exchange (ETDEWEB)

    Russow, R.; Knappe, S. [UFZ - Umweltforschungszentrum Leipzig-Halle GmbH, Bad Lauchstaedt (Germany). Sektion Bodenforschung

    1999-02-01

    Tracers are an ideal means of studying water movement and associated nitrate displacement. Often bromide is preferred as a tracer because it is considered a representative tracer for water and because, being a conservative tracer (i.e. not involved in chemical and biological soil processes), it can be used for studying anion transport in soils. Moreover, it is less expensive and easier to measure than the stable isotopes deuterium and {sup 15}N. Its great advantage over radioactive tracers (e.g. tritium), which outweighs their extreme sensitivity and ease of measurement and which it has in common with stable isotopes, is that it does not require radiation protection measures. However, there are also constraints on the use of bromide as a tracer in soil/water/plant systems. Our own studies on different soils using D{sub 2}O, bromide and [{sup 15}N]-nitrate in lysimeters suggest that the above assumptions on bromide tracers need not always be valid under conditions as they prevail in biologically active soils. As the present paper shows, these studies permit a good assessment of the possibilities and limits to these tracers. [Deutsch] Fuer die Untersuchung der Wasserbewegung sowie der daran gekoppelten Nitrat-Verlagerung ist der Einsatz von Tracern das Mittel der Wahl. Dabei wird Bromid als Tracer haeufig bevorzugt, da es allgemein als ein repraesentativer Tracer fuer Wasser und als konservativer Tracer (nicht involviert in chemische und biologische Bodenprozesse) zur Untersuchung des Anionentransportes in Boeden angesehen wird und es gegenueber den stabilen Isotopen Deuterium und {sup 15}N billiger und einfacher zu bestimmen ist. Gegenueber den radioaktiven Tracern (z.B. Tritium), die zwar sehr empfindlich und einfach messbar sind, besteht der grosse Vorteil, dass, wie bei den stabilen Isotopen, keine Strahlenschutzmassnahmen ergriffen werden muessen. Es gibt jedoch auch einschraenkende Hinweise fuer die Verwendung von Bromid als Tracer im System Boden

  16. Thermal tracer tomography: from numerical simulation to field implementation

    Science.gov (United States)

    Somogyvári, Márk; Brauchler, Ralf; Bayer, Peter

    2016-04-01

    Choosing heat for subsurface investigations is attractive because changes in temperature can be easily measured, and natural variations are typically slower than the timescale of the experiments. The tomographical setup expands the applicability of such tests to reconstruct the spatial distribution of hydraulic aquifer properties. A new inversion methodology is presented for thermal tracer tomography, using tracer travel times to invert the hydraulic conductivity distribution of the aquifer. If we can assume that heat transport is driven by advection, the travel time of the thermal tracer can be related to the hydraulic parameters of the aquifer. With this assumption other thermal effects such as thermal diffusion or density driven flow appear as noise in the results. To reduce these effects the early time diagnostics of the recorded breakthrough curves are used, focusing on the fastest transport routes between the sources and receivers. The inverse problem of the experiment thus can be formulated as a classical travel time problem, and it can be solved using standard eikonal solver algorithms known from seismic or hydraulic tomography. The method is demonstrated with a high resolution 3-D aquifer analog dataset. The generated 3-D reconstruction reveals the potential of the method, especially in finding the preferential flow paths within the aquifer. Aside from this, the developed method is computationally efficient and can provide results in a fragment of the time required for full-physics model calibration. The method is also tested under field conditions. Four heat tracer injections were performed during a three day field campaign at the Widen field site in northeast Switzerland. Pulse signals were used and the temperature evolution was measured downstream using a distributed measurement system. The preliminary results of the tomographic inversion correspond well with the findings of earlier studies from the field site imaging the same geological features as

  17. A tracer bolus method for investigating glutamine kinetics in humans.

    Directory of Open Access Journals (Sweden)

    Maiko Mori

    Full Text Available Glutamine transport between tissues is important for the outcome of critically ill patients. Investigation of glutamine kinetics is, therefore, necessary to understand glutamine metabolism in these patients in order to improve future intervention studies. Endogenous glutamine production can be measured by continuous infusion of a glutamine tracer, which necessitates a minimum measurement time period. In order to reduce this problem, we used and validated a tracer bolus injection method. Furthermore, this method was used to measure the glutamine production in healthy volunteers in the post-absorptive state, with extra alanine and with glutamine supplementation and parenteral nutrition. Healthy volunteers received a bolus injection of [1-13C] glutamine, and blood was collected from the radial artery to measure tracer enrichment over 90 minutes. Endogenous rate of appearance (endoRa of glutamine was calculated from the enrichment decay curve and corrected for the extra glutamine supplementation. The glutamine endoRa of healthy volunteers was 6.1±0.9 µmol/kg/min in the post-absorptive state, 6.9±1.0 µmol/kg/min with extra alanyl-glutamine (p = 0.29 versus control, 6.1±0.4 µmol/kg/min with extra alanine only (p = 0.32 versus control, and 7.5±0.9 µmol/kg/min with extra alanyl-glutamine and parenteral nutrition (p = 0.049 versus control. In conclusion, a tracer bolus injection method to measure glutamine endoRa showed good reproducibility and small variation at baseline as well as during parenteral nutrition. Additionally, we showed that parenteral nutrition including alanyl-glutamine increased glutamine endoRa in healthy volunteers, which was not attributable to the alanine part of the dipeptide.

  18. PET and SPET tracers for mapping the cardiac nervous system

    Energy Technology Data Exchange (ETDEWEB)

    Langer, Oliver; Halldin, Christer [Department of Clinical Neuroscience, Psychiatry Section, Karolinska Institute, Karolinska Hospital, 17176 Stockholm (Sweden)

    2002-03-01

    The human cardiac nervous system consists of a sympathetic and a parasympathetic branch with (-)-norepinephrine and acetylcholine as the respective endogenous neurotransmitters. Dysfunction of the cardiac nervous system is implicated in various types of cardiac disease, such as heart failure, myocardial infarction and diabetic autonomic neuropathy. In vivo assessment of the distribution and function of cardiac sympathetic and parasympathetic neurones with positron emission tomography (PET) and single-photon emission tomography (SPET) can be achieved by means of a number of carbon-11-, fluorine-18-, bromine-76- and iodine-123-labelled tracer molecules. Available tracers for mapping sympathetic neurones can be divided into radiolabelled catecholamines, such as 6-[{sup 18}F]fluorodopamine, (-)-6-[{sup 18}F]fluoronorepinephrine and (-)-[{sup 11}C]epinephrine, and radiolabelled catecholamine analogues, such as [{sup 123}I]meta-iodobenzylguanidine, [{sup 11}C]meta-hydroxyephedrine, [{sup 18}F]fluorometaraminol, [{sup 11}C]phenylephrine and meta-[{sup 76}Br]bromobenzylguanidine. Resistance to metabolism by monoamine oxidase and catechol-O-methyl transferase simplifies the myocardial kinetics of the second group. Both groups of compounds are excellent agents for an overall assessment of sympathetic innervation. Biomathematical modelling of tracer kinetics is complicated by the complexity of the steps governing neuronal uptake, retention and release of these agents as well as by their high neuronal affinity, which leads to partial flow dependence of uptake. Mapping of cardiac parasympathetic neurones is limited by a low density and focal distribution pattern of these neurones in myocardium. Available tracers are derivatives of vesamicol, a molecule that binds to a receptor associated with the vesicular acetylcholine transporter. Compounds like (-)-[{sup 18}F]fluoroethoxybenzovesamicol display a high degree of non-specific binding in myocardium which restricts their utility

  19. Design and Fabrication of a Prototype Tracer Surveillance Tester

    Science.gov (United States)

    1983-06-01

    problem with reproducibility and reliability at low spin rates. (6) The existing light sensor assembly and optico - electronic conditioning circuitry...is quite useful to redesign the light sensor assembly/ optico -electronic circuitry so as to obtain quantitative information on the actual intensity...pressurization/depressurization characteristics 31 of the combustion chamber 8a Oscilloscope trace of tracer RPM and light sensor output for 32 30,000

  20. nTRACER/COBRA-TF Coupling and Initial Assessment

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jaejin; Joo, Han Gyu [Seoul National University, Seoul (Korea, Republic of); Perin, Yann; Velkov, Kiril [GRS, Garching (Germany)

    2015-05-15

    The nTRACER direct whole core calculation code being developed at Seoul National University (SNU) has an internal T/H module to determine the temperature and density fields in the reactor. However, this module is based on a quite simplified model and considers only axial flow. The weakness of not-considering radial flow was overcome by coupling the MATRA (Multichannel Analysis for steady-state and Transient in Rod Array) code with nTRACER. MATRA can generate more realistic and detailed T/H field information for nTRACER, but it is a legacy code and does not have an efficient parallel computing capability. On the contrary, the COBRA-TF (Coolant-Boiling in Rod Arrays Two Fluids, CTF) subchannel code, which was developed for the T/H analysis of Light Water Reactor (LWR) vessels, has a good parallel computing capability based on the Message Passing Interface (MPI). The initial assessment of the coupled code demonstrates that more realistic coolant temperatures are obtainable by using CTF. The change in pin power distribution is noted with the realistic flow distribution even though the change is insignificant. The calculation utilizing the boron tracking model of CTF is noticeable. It makes possible for nTRACER to handle nonuniform boron distributions which can be encountered during some transients. Since further validation of the coupling is necessary, the coupling capabilities will be extended to transient applications where non-uniform distributions of inlet parameters such as boron concentration but also coolant temperature can occur.

  1. Evaluation of anthropogenic secondary organic aerosol tracers from aromatic hydrocarbons

    Science.gov (United States)

    Al-Naiema, Ibrahim M.; Stone, Elizabeth A.

    2017-02-01

    Products of secondary organic aerosol (SOA) from aromatic volatile organic compounds (VOCs) - 2,3-dihydroxy-4-oxopentanoic acid, dicarboxylic acids, nitromonoaromatics, and furandiones - were evaluated for their potential to serve as anthropogenic SOA tracers with respect to their (1) ambient concentrations and detectability in PM2.5 in Iowa City, IA, USA; (2) gas-particle partitioning behaviour; and (3) source specificity by way of correlations with primary and secondary source tracers and literature review. A widely used tracer for toluene-derived SOA, 2,3-dihydroxy-4-oxopentanoic acid was only detected in the particle phase (Fp = 1) at low but consistently measurable ambient concentrations (averaging 0.3 ng m-3). Four aromatic dicarboxylic acids were detected at relatively higher concentrations (9.1-34.5 ng m-3), of which phthalic acid was the most abundant. Phthalic acid had a low particle-phase fraction (Fp = 0.26) likely due to quantitation interferences from phthalic anhydride, while 4-methylphthalic acid was predominantly in the particle phase (Fp = 0.82). Phthalic acid and 4-methylphthalic acid were both highly correlated with 2,3-dihydroxy-4-oxopentanoic acid (rs = 0.73, p = 0.003; rs = 0.80, p hydrocarbons; however the substantial partitioning toward the gas phase (Fp ≤ 0.16) and their water sensitivity limit their application as tracers. The outcome of this study is the demonstration that 2,3-dihydroxy-4-oxopentanoic acid, phthalic acid, 4-methylphthalic acid, and 4-hydroxy-3-nitrobenzyl alcohol are good candidates for tracing SOA from aromatic VOCs.

  2. Application of neutron activation tracer sediment technique on environmental science

    Institute of Scientific and Technical Information of China (English)

    YinYi; ZhongWei-Ni; 等

    1997-01-01

    Field and laboratory inverstigations were carried out to study the transport and dispersion law of polluted sediments near wastewater outlet using neutron activation tracer technique.The direction of transport and dispersion of polluted sediments,dispersion amount in different directions,sedimentary region of polluted sediment and evaluation of polluted risk are given.This provided a new test method for the study of environmental science and added a new forecasted content for the evaluation of environmental influence.

  3. Application of separable parameter space techniques to multi-tracer PET compartment modeling

    Science.gov (United States)

    Zhang, Jeff L.; Morey, A. Michael; Kadrmas, Dan J.

    2016-02-01

    Multi-tracer positron emission tomography (PET) can image two or more tracers in a single scan, characterizing multiple aspects of biological functions to provide new insights into many diseases. The technique uses dynamic imaging, resulting in time-activity curves that contain contributions from each tracer present. The process of separating and recovering separate images and/or imaging measures for each tracer requires the application of kinetic constraints, which are most commonly applied by fitting parallel compartment models for all tracers. Such multi-tracer compartment modeling presents challenging nonlinear fits in multiple dimensions. This work extends separable parameter space kinetic modeling techniques, previously developed for fitting single-tracer compartment models, to fitting multi-tracer compartment models. The multi-tracer compartment model solution equations were reformulated to maximally separate the linear and nonlinear aspects of the fitting problem, and separable least-squares techniques were applied to effectively reduce the dimensionality of the nonlinear fit. The benefits of the approach are then explored through a number of illustrative examples, including characterization of separable parameter space multi-tracer objective functions and demonstration of exhaustive search fits which guarantee the true global minimum to within arbitrary search precision. Iterative gradient-descent algorithms using Levenberg-Marquardt were also tested, demonstrating improved fitting speed and robustness as compared to corresponding fits using conventional model formulations. The proposed technique overcomes many of the challenges in fitting simultaneous multi-tracer PET compartment models.

  4. Radioisotope tracer study in a sludge hygienization research irradiator (SHRI).

    Science.gov (United States)

    Pant, H J; Thýn, J; Zitný, R; Bhatt, B C

    2001-01-01

    A radioisotope tracer study has been carried out in a batch type sludge hygienization research irradiator with flow from top to bottom, the objective being to measure flow rate, circulation and mixing times and to investigate the hydrodynamic behaviour of the irradiator for identifying the cause(s) of malfunction. A stimulus-response technique with NH4(82)Br as a tracer was used to measure the above parameters. Experiments were carried out at three different flow rates, i.e 1.0, 0.64 and 0.33 m3/min. Three combined models based on a set of differential equations are proposed and used to simulate the measured tracer concentration curves. The obtained parameters were used to estimate dead volume and analyse hydrodynamic behaviour of the irradiator. The nonlinear regression problem of model parameter estimation was solved using the Marquardt-Levenberg method. The measured flow rate was found to be in good agreement with the values shown by the flow meter. The circulation times were found to be half of the mixing times. A simple approach for estimation of dose based on a known vertical dose-rate profile inside the irradiator is presented. About one-fourth of the volume of the irradiator was found to be dead at lower flow rates and this decreased with increase in flow rate. At higher flow rates, a semi stagnant volume was found with slow exchange of flow between the active and dead volumes.

  5. Radioisotope tracer study in a sludge hygienization research irradiator (SHRI)

    Energy Technology Data Exchange (ETDEWEB)

    Pant, H.J. E-mail: hjpant@aspsara.barc.ernet.in; Thyn, J.; Zitny, R.; Bhatt, B.C

    2001-01-15

    A radioisotope tracer study has been carried out in a batch type sludge hygienization research irradiator with flow from top to bottom, the objective being to measure flow rate, circulation and mixing times and to investigate the hydrodynamic behaviour of the irradiator for identifying the cause(s) of malfunction. A stimulus-response technique with NH{sup 82}{sub 4}Br as a tracer was used to measure the above parameters. Experiments were carried out at three different flow rates, i.e 1.0, 0.64 and 0.33 m{sup 3}/min. Three combined models based on a set of differential equations are proposed and used to simulate the measured tracer concentration curves. The obtained parameters were used to estimate dead volume and analyse hydrodynamic behaviour of the irradiator. The nonlinear regression problem of model parameter estimation was solved using the Marquardt-Levenberg method. The measured flow rate was found to be in good agreement with the values shown by the flow meter. The circulation times were found to be half of the mixing times. A simple approach for estimation of dose based on a known vertical dose-rate profile inside the irradiator is presented. About one-fourth of the volume of the irradiator was found to be dead at lower flow rates and this decreased with increase in flow rate. At higher flow rates, a semi stagnant volume was found with slow exchange of flow between the active and dead volumes.

  6. Lattice-Boltzmann Simulations of Microswimmer-Tracer Interactions

    CERN Document Server

    de Graaf, Joost

    2016-01-01

    Hydrodynamic interactions in systems comprised of self-propelled particles, such as swimming microorganisms, and passive tracers have a significant impact on the tracer dynamics compared to the equivalent "dry" sample. However, such interactions are often difficult to take into account in simulations due to their computational cost. Here, we perform a systematic investigation of swimmer-tracer interaction using an efficient force/counter-force based lattice-Boltzmann (LB) algorithm [J. de Graaf~\\textit{et al.}, J. Chem. Phys.~\\textbf{144}, 134106 (2016)], in order to validate its applicability to study large-scale microswimmer suspensions. We show that the LB algorithm reproduces far-field theoretical results well, both in a system with periodic boundary conditions and in a spherical cavity with no-slip walls, for which we derive expressions here. The LB algorithm has an inherent near-field renormalization of the flow field, due to the force interpolation between the swimmers and the lattice. This strongly pe...

  7. Consistency Problem with Tracer Advection in the Atmospheric Model GAMIL

    Institute of Scientific and Technical Information of China (English)

    ZHANG Kai; WAN Hui; WANG Bin; ZHANG Meigen

    2008-01-01

    The radon transport test,which is a widely used test case for atmospheric transport models,is carried out to evaluate the tracer advection schemes in the Grid-Point Atmospheric Model of IAP-LASG (GAMIL).TWO of the three available schemes in the model are found to be associated with significant biases in the polar regions and in the upper part of the atmosphere,which implies potentially large errors in the simulation of ozone-like tracers.Theoretical analyses show that inconsistency exists between the advection schemes and the discrete continuity equation in the dynamical core of GAMIL and consequently leads to spurious sources and sinks in the tracer transport equation.The impact of this type of inconsistency is demonstrated by idealized tests and identified as the cause of the aforementioned biases.Other potential effects of this inconsistency are also discussed.Results of this study provide some hints for choosing suitable advection schemes in the GAMIL model.At least for the polar-region-concentrated atmospheric components and the closely correlated chemical species,the Flux-Form Semi-Lagrangian advection scheme produces more reasonable simulations of the large-scale transport processes without significantly increasing the computational expense.

  8. Metal stable isotope signatures as tracers in environmental geochemistry.

    Science.gov (United States)

    Wiederhold, Jan G

    2015-03-03

    The biogeochemical cycling of metals in natural systems is often accompanied by stable isotope fractionation which can now be measured due to recent analytical advances. In consequence, a new research field has emerged over the last two decades, complementing the traditional stable isotope systems (H, C, O, N, S) with many more elements across the periodic table (Li, B, Mg, Si, Cl, Ca, Ti, V, Cr, Fe, Ni, Cu, Zn, Ge, Se, Br, Sr, Mo, Ag, Cd, Sn, Sb, Te, Ba, W, Pt, Hg, Tl, U) which are being explored and potentially applicable as novel geochemical tracers. This review presents the application of metal stable isotopes as source and process tracers in environmental studies, in particular by using mixing and Rayleigh model approaches. The most important concepts of mass-dependent and mass-independent metal stable isotope fractionation are introduced, and the extent of natural isotopic variations for different elements is compared. A particular focus lies on a discussion of processes (redox transformations, complexation, sorption, precipitation, dissolution, evaporation, diffusion, biological cycling) which are able to induce metal stable isotope fractionation in environmental systems. Additionally, the usefulness and limitations of metal stable isotope signatures as tracers in environmental geochemistry are discussed and future perspectives presented.

  9. Studies of Tracer Dispersion and Fluid Flow in Porous Media

    Energy Technology Data Exchange (ETDEWEB)

    Rage, T.

    1996-12-31

    This doctoral thesis explores the connection between the topology of a porous medium and its macroscopic transport properties and is based on computerized simulation. In porous media, both diffusion and convection contribute to the dispersion of a tracer and their combined effect is emphasized. The governing equations are solved numerically, using finite differences and Monte Carlo technique. The influence of finite Reynolds number on the outcome of echo-experiments is discussed. Comparing experiments and simulations it is found that nonlinear inertial forces lead to a visible deformation of a returned tracer at surprisingly small Reynolds numbers. In a study of tracer dispersion and fluid flow in periodic arrays of discs it is demonstrated that the mechanisms of mechanical dispersion in periodic media and in natural (non-periodic) porous media are essentially different. Measurements of the percolation probability distribution of a sandstone sample is presented. Local porosity theory predicts that this simple geometric function of a porous medium is of dominant importance for its macroscopic transport properties. It is demonstrated that many aspects of transport through fractures can be studied by using simple but realistic models and readily available computer resources. An example may be the transport of hydrocarbon fluids from the source rock to a reservoir. 165 refs., 44 figs., 1 table

  10. Radon as tracer to identify discharge sections at Juatuba basin

    Energy Technology Data Exchange (ETDEWEB)

    Chagas, Claudio Jose; Ferreira, Vinicius Verna Magalhaes; Fonseca, Raquel Luisa Mageste; Rocha, Zildete; Moreira, Rubens Martins; Lemos, Nayron Cosme; Menezes, Angela de Barros Correia, E-mail: vvmf@cdtn.br, E-mail: rlmf@cdtn.br, E-mail: cjc@cdtn.br, E-mail: rochaz@cdtn.br, E-mail: rubens@cdtn.br, E-mail: menezes@cdtn.br, E-mail: lemosnc@cdtn.br [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil); Santos, Talita Oliveira, E-mail: talitaolsantos@yahoo.com.br [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Escola de Engenharia. Departamento de Engenharia Nuclear. Programa de Pos-Graduacao em Ciencias e Tecnicas Nucleares

    2015-07-01

    The use of natural tracers in hydrological studies is a very useful tool, being applied in several studies. One of these tracers is the radon, {sup 222}Rn, noble gas derived from natural sources, been found in all underground waters, as a product of radioactive decay of the {sup 226}Ra. This gas can be found in the air, water, rocks or soil. In this paper, the {sup 222}Rn detection in surface water was used as tracer in order to identify aquifer discharge sections in surface water at the Fundao stream, which belongs to the Juatuba river basin, through the second semester of 2014 and the first semester of 2015, in three sampling campaigns. The {sup 222}Rn measurements at Fundao stream were carried out using the equipment RAD 7. The results showed that {sup 222}Rn is present in some sections of the water course suggesting that there is a connection between groundwater and surface water. It also justifies the variation in the water level in the stream, recorded by a fluviometric station. (author)

  11. An investigation of radial tracer flow in naturally fractured reservoirs

    Energy Technology Data Exchange (ETDEWEB)

    Jetzabeth, Ramirez-Sabag; Fernando, Samaniego V.; Jesus, Rivera R.; Fernando Rodriguez

    1991-01-01

    This study presents a general solution for the radial flow of tracers in naturally fractured reservoirs. Continuous and finite step injection of chemical and radioactive tracers are considered. The reservoir is treated as being composed of two regions: a mobile region where longitudinal dispersion and convection take place and a stagnant region where only diffusion and adsorption are allowed. Radioactive decay is considered in both regions. The model of this study is thoroughly compared to those previously presented in literature by Moench and Ogata, Tang et al., Chen et al., and Hsieh et al. The solution is numerically inverted by means of the Crump algorithm. A detailed validation of the model with respect to solutions previously presented and/or simplified physical conditions solutions (i.e., homogeneous case) or limit solutions (i.e., for short times) was carried out. The influence of various dimensionless parameters that enter into the solution was investigated. A discussion of results obtained through the Crump and Stehfest algorithm is presented, concluding that the Crump method provides more reliable tracer concentrations.

  12. Using atmospheric tracers to reduce uncertainty in groundwater recharge areas.

    Science.gov (United States)

    Starn, J Jeffrey; Bagtzoglou, Amvrossios C; Robbins, Gary A

    2010-01-01

    A Monte Carlo-based approach to assess uncertainty in recharge areas shows that incorporation of atmospheric tracer observations (in this case, tritium concentration) and prior information on model parameters leads to more precise predictions of recharge areas. Variance-covariance matrices, from model calibration and calculation of sensitivities, were used to generate parameter sets that account for parameter correlation and uncertainty. Constraining parameter sets to those that met acceptance criteria, which included a standard error criterion, did not appear to bias model results. Although the addition of atmospheric tracer observations and prior information produced similar changes in the extent of predicted recharge areas, prior information had the effect of increasing probabilities within the recharge area to a greater extent than atmospheric tracer observations. Uncertainty in the recharge area propagates into predictions that directly affect water quality, such as land cover in the recharge area associated with a well and the residence time associated with the well. Assessments of well vulnerability that depend on these factors should include an assessment of model parameter uncertainty. A formal simulation of parameter uncertainty can be used to delineate probabilistic recharge areas, and the results can be expressed in ways that can be useful to water-resource managers. Although no one model is the correct model, the results of multiple models can be evaluated in terms of the decision being made and the probability of a given outcome from each model.

  13. Application of transition metal isotope tracers in global change research

    Institute of Scientific and Technical Information of China (English)

    SONG Jinming; Thomas F. Pedersen

    2005-01-01

    High-precision isotope composition determinations using multicollector, magnetic-sector inductively coupled plasma mass spectrometry (MC-ICPMS) have recently revealed that some transition metal isotopes such as those of Mo, Fe, Cu, Zn etc. can be used as biogeochemical tracers in global change research.The Mo isotope system may be useful in paleoredox investigations indicating that δ 97/95Mo in seawater may co-vary with changes in the relative proportions of anoxic and oxic sedimentation in the ocean, and that this variation may be recorded in δ 97/95Mo of anoxic sediments. The Mo continental flux into the oceans and the global Mo isotope budget can be estimated fromδ 97/95MO values. The Fe isotope composition in seawater is an important issue because Fe plays a controlling role in biological productivity in the oceans and its abundance in seawater may have substantial effect on climate changes. Iron isotope fractionations could result from bio- and abio-processes and have about 0.1% variation (δ 56/54Fe), so Fe isotopes considered alone cannot be used to distinguish the products of abiotic and biotic Fe processing in geological records. Cu and Zn isotopes are also used as biogeochemical tracers, but the researches are relatively less. This review mainly focuses on the methods for preparation, purification and determination of new isotope tracer samples, and on isotope applications in marine environmental changes.

  14. Cosmological constraints from multiple tracers in spectroscopic surveys

    CERN Document Server

    Alarcon, Alex; Gaztañaga, Enrique

    2016-01-01

    We use the Fisher matrix formalism to study the expansion and growth history of the Universe using galaxy clustering with 2D angular cross-correlation tomography in spectroscopic or high resolution photometric redshift surveys. The radial information is contained in the cross correlations between narrow redshift bins. We show how multiple tracers with redshift space distortions cancel sample variance and arbitrarily improve the constraints on the dark energy equation of state $\\omega(z)$ and the growth parameter $\\gamma$ in the noiseless limit. The improvement for multiple tracers quickly increases with the bias difference between the tracers, up to a factor $\\sim4$ in $\\text{FoM}_{\\gamma\\omega}$. We model a magnitude limited survey with realistic density and bias using a conditional luminosity function, finding a factor 1.3-9.0 improvement in $\\text{FoM}_{\\gamma\\omega}$ -- depending on global density -- with a split in a halo mass proxy. Partly overlapping redshift bins improve the constraints in multiple tr...

  15. In-Situ Characterization of Dense Non-Aqueous Phase Liquids Using Partitioning Tracers

    Energy Technology Data Exchange (ETDEWEB)

    Gary A. Pope; Daene C. McKinney; Akhil Datta Gupta; Richard E. Jackson; Minquan Jin

    2000-03-20

    Majors advances have been made during the past three years in our research on interwell partitioning tracers tests (PITTs). These advances include (1) progress on the inverse problem of how to estimate the three-dimensional distribution of NAPL in aquifers from the tracer data, (2) the first ever partitioning tracer experiments in dual porosity media, (3) the first modeling of partitioning tracers in dual porosity media (4) experiments with complex NAPLs such as coal tar, (5) the development of an accurate and simple method to predict partition coefficients using the equivalent alkane carbon number approach, (6) partitioning tracer experiments in large model aquifers with permeability layers, (7) the first ever analysis of partitioning tracer data to estimate the change in composition of a NAPL before and after remediation (8) the first ever analysis of partitioning tracer data after a field demonstration of surfactant foam to remediate NAPL and (9) experiments at elevated temperatures .

  16. Entropically induced asymmetric passage times of charged tracers across corrugated channels.

    Science.gov (United States)

    Malgaretti, Paolo; Pagonabarraga, Ignacio; Rubi, J Miguel

    2016-01-21

    We analyze the diffusion of charged and neutral tracers suspended in an electrolyte embedded in a channel of varying cross section. Making use of systematic approximations, the diffusion equation governing the motion of tracers is mapped into an effective 1D equation describing the dynamics along the longitudinal axis of the channel where its varying-section is encoded as an effective entropic potential. This simplified approach allows us to characterize tracer diffusion under generic confinement by measuring their mean first passage time (MFPT). In particular, we show that the interplay between geometrical confinement and electrostatic interactions strongly affect the MFTP of tracers across corrugated channels hence leading to alternative means to control tracers translocation across charged pores. Finally, our results show that the MFPTs of a charged tracer in opposite directions along an asymmetric channel may differ We expect our results to be relevant for biological as well synthetic devices whose dynamics is controlled by the detection of diluted tracers.

  17. Entropically induced asymmetric passage times of charged tracers across corrugated channels

    Energy Technology Data Exchange (ETDEWEB)

    Malgaretti, Paolo, E-mail: malgaretti@is.mpg.de [Max-Planck-Institut für Intelligente Systeme, Heisenbergstr. 3, D-70569 Stuttgart (Germany); IV Institut für Theoretische Physik, Universität Stuttgart, Pfaffenwaldring 57, D-70569 Stuttgart (Germany); Department de Fisica Fonamental, Universitat de Barcelona, Barcelona (Spain); Pagonabarraga, Ignacio; Miguel Rubi, J. [Department de Fisica Fonamental, Universitat de Barcelona, Barcelona (Spain)

    2016-01-21

    We analyze the diffusion of charged and neutral tracers suspended in an electrolyte embedded in a channel of varying cross section. Making use of systematic approximations, the diffusion equation governing the motion of tracers is mapped into an effective 1D equation describing the dynamics along the longitudinal axis of the channel where its varying-section is encoded as an effective entropic potential. This simplified approach allows us to characterize tracer diffusion under generic confinement by measuring their mean first passage time (MFPT). In particular, we show that the interplay between geometrical confinement and electrostatic interactions strongly affect the MFTP of tracers across corrugated channels hence leading to alternative means to control tracers translocation across charged pores. Finally, our results show that the MFPTs of a charged tracer in opposite directions along an asymmetric channel may differ We expect our results to be relevant for biological as well synthetic devices whose dynamics is controlled by the detection of diluted tracers.

  18. Synthesis, Anti-Breast Cancer Activity, and Molecular Docking Study of a New Group of Acetylenic Quinolinesulfonamide Derivatives

    Directory of Open Access Journals (Sweden)

    Krzysztof Marciniec

    2017-02-01

    Full Text Available In this study, a series of regioisomeric acetylenic sulfamoylquinolines are designed, synthesized, and tested in vitro for their antiproliferative activity against three human breast cacer cell lines (T47D, MCF-7, and MDA-MB-231 and a human normal fibroblast (HFF-1 by 4-[3-(4-iodophenyl-2-(4-nitrophenyl-2H-5-tetrazolio]-1,3-benzene disulfonate (WST-1 assay. The antiproliferative activity of the tested acetylenic quinolinesulfonamides is comparable to that of cisplatin. The bioassay results demonstrate that most of the tested compounds show potent antitumor activities, and that some compounds exhibit better effects than the positive control cisplatin against various cancer cell lines. Among these compounds, 4-(3-propynylthio-7-[N-methyl-N-(3-propynylsulfamoyl]quinoline shows significant antiprolierative activity against T47D cells with IC50 values of 0.07 µM. In addition, 2-(3-Propynylthio-6-[N-methyl-N-(3-propynylsulfa-moyl]quinoline and 2-(3-propynylseleno-6-[N-methyl-N-(3-propynylsulfamoyl]quinoline display highly effective atitumor activity against MDA-MB-231 cells, with IC50 values of 0.09 and 0.50 µM, respectively. Furthermore, most of the tested compounds show a weak cytotoxic effect against the normal HFF-1 cell line. Additionally, in order to suggest a mechanism of action for their activity, all compounds are docked into the binding site of two human cytochrome P450 (CYP isoenzymes. These data indicate that some of the title compounds display significant cytotoxic activity, possibly targeting the CYPs pathways.

  19. Interpretation of Water Tracer Simulation in the H-1 Segment of the Gullfaks Field

    Energy Technology Data Exchange (ETDEWEB)

    Moid, Farrukh

    2000-07-01

    This thesis describes the water tracer simulation in the H-1 segment of the Gullfaks field. Three passive water tracer slugs were injected from the two producing wells during water flooding, pressure maintenance and reservoir monitoring program in the Gullfaks field. The same program is considered in this thesis. Computer Modelling Group's (CMG) simulator STARS is used for the general reservoir simulation and a separate module for tracer flow (ITRC-SIM) which is incorporated in the STARS and developed at Institute For Energy (IFE) is used for the tracer simulation. Water cut and tracer concentration data are used in history matching of the field. History matching is performed by changing the transmissibility and permeability of different layers; also the effect of changing saturations near the well bore on history matching is examined. It is noted that water cut is sensitive to transmissibility of the layers and the saturation around the well bore. Tracers are found to be moving in the most permeable layers. The corresponding history matching of water and tracer production shows a severe loss of first tracer injected because of imbibition process. Water phase velocity and areal communication between different wells are determined. Advance numerical features of tracer module ITRC-SIM such as flux limiting scheme and grid refinement scheme are evaluated and are found to be an important tool for reducing the numerical smearing. The effects of dispersion and diffusion on tracer response curve are also evaluated. Dispersion makes the tracer concentration curve smeared. Simulation results of water cut and tracer concentration show a good history match for this reservoir. The improved simulation model and the tracer module for this reservoir can be used for the prediction of future performance of the reservoir and interpretation of the tracer behaviour in the reservoir. (author)

  20. Evaluating Chemical Tracers in Suburban Groundwater as Indicators of Nitrate-Nitrogen Sources

    Science.gov (United States)

    Nitka, A.; DeVita, W. M.; McGinley, P.

    2015-12-01

    The CDC reports that over 15 million US households use private wells. These wells are vulnerable to contamination. One of the most common contaminants in private wells is nitrate. Nitrate has a health standard of 10 mg/L. This standard is set to prevent methemaglobinemia, or "blue baby" syndrome, in infants. In extreme cases it can affect breathing and heart function, and even lead to death. Elevated nitrate concentrations have also been associated with increased risk of thyroid disease, diabetes, and certain types of cancer. Unlike municipal wells, there is no mandatory testing of private wells. It is the responsibility of users to have their well water tested. The objective of this research was to identify the most useful chemical tracers for determining sources of nitrate in private water supplies. Chemical characteristics, such as mobility in groundwater and water solubility, as well as frequency of use, were considered when choosing source indicators. Fourteen pharmaceuticals and personal care products unique to human use were chosen to identify wells impacted by septic waste. A bovine antibiotic and five pesticide metabolites were used to identify contamination from agricultural sources. Eighteen private wells were selected in a suburban area with septic systems and adjacent agricultural land. The wells were sampled five times and analyzed to provide a temporal profile of nitrate and the tracers. The artificial sweetener sucralose was found in >70% of private wells. Wells with sucralose detected had nitrate concentrations between 5-15 mg/L. The herbicide metabolite metolachlor ESA was detected in 50% of the wells. These wells typically had the highest nitrate concentrations, often >10 mg/L. The common use and frequent detection of these two compounds made them the most reliable indicators of nitrate sources evaluated in this study. This information will help well owners determine appropriate treatment and remediation options and could direct future

  1. A comparison of resting images from two myocardial perfusion tracers

    Energy Technology Data Exchange (ETDEWEB)

    Anagnostopoulos, C. [Royal Brompton Hospital, London (United Kingdom); Laney, R. [Royal Brompton Hospital, London (United Kingdom); Pennell, D. [National Heart and Lung Inst., London (United Kingdom); Proukakis, H. [University of Athens Medical School (Greece); Underwood, R. [National Heart and Lung Inst., London (United Kingdom)

    1995-09-01

    We have compared stress-redistribution and delayed rest thallium-201 with rest technetium-99m methoxyisobutylisonitrile (MIBI) tomograms in order to compare the tracers for the assessment of myocardial viability and to validate a rapid protocol combining the two tracers. We studied 30 consecutive patients with known or suspected coronary artery disease [group 1: 16 with normal left ventricular function, mean left ventricular ejection fraction (LVEF) 55%, SD 6%; group 2: 14 with abnormal function, mean LVEF 28%, SD 8%]. {sup 201}Tl was injected during infusion of adenosine followed by acquisition of conventional stress and redistribution tomograms. On a separate day, {sup 201}Tl was injected at rest with imaging 4 h later. {sup 99m}Tc-MIBI was then given at rest and imaging was performed. Three images were compared: redistribution {sup 201}Tl, rest {sup 201}Tl, and rest {sup 99m}Tc-MIBI. Tracer activity was classified visually and quantitatively in nine segments and segments with>50% activity were defined as containing clinically significant viable myocardium. Mean global tracer uptake as a percentage of maximum was similar in group 1 (rest {sup 201}Tl 69%{+-}12%, redistribution {sup 201}Tl 69%{+-}15%, rest {sup 99m}Tc-MIBI 70%{+-}13%), but in group 2 mean tracer uptake was significantly greater in the rest {sup 201}Tl images (59%{+-}16%) than in redistribution {sup 201}Tl images (53%{+-}17%) or rest {sup 99m}Tc-MIBI images (53%{+-}19%). Overall agreement for regional uptake score was excellent ({kappa} from 0.79 to 0.84), although there were a significant number of segments with less uptake shown by redistribution {sup 201}Tl and by rest {sup 99m}Tc-MIBI than by rest {sup 201}Tl in group 2. The number of segments with significant viable myocardium in group 1 was very similar between the three images but in group 2 rest {sup 201}Tl identified significantly more segments as viable than the other images. (orig./MG) (orig.). With 1 fig., 7 tabs.

  2. Estimation of Fluorescent Dye Amount in Tracer Dye Test

    Science.gov (United States)

    Pekkan, Emrah; Balkan, Erman; Balkan, Emir

    2015-04-01

    Karstic groundwater is more influenced by human than the groundwater that disperse in pores. On the other hand karstic groundwater resources, in addition to providing agricultural needs, livestock breeding, drinking and domestic water in most of the months of the year, they also supply drinking water to the wild life at high altitudes. Therefore sustainability and hydrogeological investigation of karstic resources is critical. Tracing techniques are widely used in hydrologic and hydrogeologic studies to determine water storage, flow rate, direction and protection area of groundwater resources. Karanfil Mountain (2800 m), located in Adana, Turkey, is one of the karstic recharge areas of the natural springs spread around its periphery. During explorations of the caves of Karanfil mountain, a 600 m deep cave was found by the Turkish and Polish cavers. At the bottom of the cave there is an underground river with a flow rate of approximately 0.5 m3/s during August 2014. The main spring is located 8 km far from the cave's entrance and its mean flow rate changes between 3.4 m3/s and 0.21 m3/s in March and September respectively according to a flowrate observation station of Directorate of Water Works of Turkey. As such frequent storms, snowmelt and normal seasonal variations in rainfall have a significant and rapid effect on the volume of this main spring resource. The objective of our research is to determine and estimate dye amount before its application on the field inspired from the previously literature on the subject. This estimation is intended to provide a preliminary application of a tracer test of a karstic system. In this study dye injection, inlet point will be an underground river located inside the cave and the observation station will be the spring that is approximately 8 km far from the cave entrance. On the other hand there is 600 meter elevation difference between cave entrance and outlet spring. In this test Rodamin-WT will be used as tracer and the

  3. MULTISPECIES REACTIVE TRACER TEST IN A SAND AND GRAVEL AQUIFER, CAPE COD, MASSACHUSETTS: PART 2: TRANSPORT OF CHROMIUM (VI) AND LEAD-, COPPER-, AND ZINC-EDTA TRACERS

    Science.gov (United States)

    This report discusses the transport of a group of reactive tracers over the course of a large-scale, natural gradient tracer test conducted at the USGS Cape Cod Toxic Substances Hydrology Research site, near Falmouth, Massachusetts. The overall objectives of the experiment were ...

  4. Design and synthesis of multifunctional poly(ethylene glycol)s using enzymatic catalysis for multivalent cancer drug delivery

    Science.gov (United States)

    Seo, Kwang Su

    The objective of this research was to design and synthesize multifunctional poly(ethylene glycol)s (PEG)s using enzyme-catalyzed reactions for multivalent targeted drug delivery. Based on computer simulation for optimum folate binding, a four-arm PEG star topology with Mn = 1000 g/mol was proposed. First, a four-functional core based on tetraethylene glycol (TEG) was designed and synthesized using transesterification and Michael addition reactions in the presence of Candida antarctica lipase B (CALB) as a biocatalyst. The four-functional core (HO)2-TEG-(OH)2 core was successfully prepared by the CALB-catalyzed transesterification of vinyl acrylate (VA) with TEG and then Michael addition of diethanolamine to the resulting TEG diacrylate with/without the use of solvent. The functional PEG arms with fluorescein isothiocyanate (FITC) and folic acid (FA) were prepared using both traditional organic chemistry and enzyme-catalyzed reactions. FITC was reacted with the amine group of H2N-PEG-OH in the presence of triethylamine via nucleophilic addition onto the isothiocyanate group. Then, divinyl adipate (DVA) was transesterified with the FITC-PEG-OH product in the presence of CALB to produce the FITC-PEG vinyl ester that will be attached to the four-functional core via CALC-catalyzed transesterification. For the synthesis of FA-PEG vinyl ester arm, DVA was first reacted with PEG-monobenzyl ether (BzPEG-OH) in bulk in the presence of CALB. The BzPEG vinyl ester was then transesterified with 12-bromo-1-dodecanol in the presence of CALB. Finally, BzPEG-Br was attached to FA exclusively in the gamma position using a new method. The thesis also discusses fundamental studies that were carried out in order to get better understanding of enzyme catalyzed transesterification and Michael addition reactions. First, in an effort to investigate the effects of reagent and enzyme concentrations in transesterification, vinyl methacrylate (VMA) was reacted with 2-(hydroxyethyl) acrylate (2

  5. An Internal Standard-Assisted Synthesis and Degradation Proteomic Approach Reveals the Potential Linkage between VPS4B Depletion and Activation of Fatty Acid β-Oxidation in Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Zhongping Liao

    2013-01-01

    Full Text Available The endosomal/lysosomal system, in particular the endosomal sorting complexes required for transport (ESCRTs, plays an essential role in regulating the trafficking and destination of endocytosed receptors and their associated signaling molecules. Recently, we have shown that dysfunction and down-regulation of vacuolar protein sorting 4B (VPS4B, an ESCRT-III associated protein, under hypoxic conditions can lead to the abnormal accumulation of epidermal growth factor receptor (EGFR and aberrant EGFR signaling in breast cancer. However, the pathophysiological consequences of VPS4B dysfunction remain largely elusive. In this study, we used an internal standard-assisted synthesis and degradation mass spectrometry (iSDMS method, which permits the direct measurement of protein synthesis, degradation and protein dynamic expression, to address the effects of VPS4B dysfunction in altering EGF-mediated protein expression. Our initial results indicate that VPS4B down-regulation decreases the expression of many proteins involved in glycolytic pathways, while increased the expression of proteins with roles in mitochondrial fatty acid β-oxidation were up-regulated in VPS4B-depleted cells. This observation is also consistent with our previous finding that hypoxia can induce VPS4B down-regulated, suggesting that the adoption of fatty acid β-oxidation could potentially serve as an alternative energy source and survival mechanism for breast cancer cells in response to hypoxia-mediated VPS4B dysfunction.

  6. Development of Models to Simulate Tracer Tests for Characterization of Enhanced Geothermal Systems

    Energy Technology Data Exchange (ETDEWEB)

    Williams, Mark D.; Reimus, Paul; Vermeul, Vincent R.; Rose, Peter; Dean, Cynthia A.; Watson, Tom B.; Newell, D.; Leecaster, Kevin; Brauser, Eric

    2013-05-01

    A recent report found that power and heat produced from enhanced (or engineered) geothermal systems (EGSs) could have a major impact on the U.S energy production capability while having a minimal impact on the environment. EGS resources differ from high-grade hydrothermal resources in that they lack sufficient temperature distribution, permeability/porosity, fluid saturation, or recharge of reservoir fluids. Therefore, quantitative characterization of temperature distributions and the surface area available for heat transfer in EGS is necessary for the design and commercial development of the geothermal energy of a potential EGS site. The goal of this project is to provide integrated tracer and tracer interpretation tools to facilitate this characterization. This project was initially focused on tracer development with the application of perfluorinated tracer (PFT) compounds, non-reactive tracers used in numerous applications from atmospheric transport to underground leak detection, to geothermal systems, and evaluation of encapsulated PFTs that would release tracers at targeted reservoir temperatures. After the 2011 midyear review and subsequent discussions with the U.S. Department of Energy Geothermal Technology Program (GTP), emphasis was shifted to interpretive tool development, testing, and validation. Subsurface modeling capabilities are an important component of this project for both the design of suitable tracers and the interpretation of data from in situ tracer tests, be they single- or multi-well tests. The purpose of this report is to describe the results of the tracer and model development for simulating and conducting tracer tests for characterizing EGS parameters.

  7. Journal: A Review of Some Tracer-Test Design Equations for ...

    Science.gov (United States)

    Determination of necessary tracer mass, initial sample-collection time, and subsequent sample-collection frequency are the three most difficult aspects to estimate for a proposed tracer test prior to conducting the tracer test. To facilitate tracer-mass estimation, 33 mass-estimation equations are reviewed here, 32 of which were evaluated using previously published tracer-test design examination parameters. Comparison of the results produced a wide range of estimated tracer mass, but no means is available by which one equation may be reasonably selected over the others. Each equation produces a simple approximation for tracer mass. Most of the equations are based primarily on estimates or measurements of discharge, transport distance, and suspected transport times. Although the basic field parameters commonly employed are appropriate for estimating tracer mass, the 33 equations are problematic in that they were all probably based on the original developers' experience in a particular field area and not necessarily on measured hydraulic parameters or solute-transport theory. Suggested sampling frequencies are typically based primarily on probable transport distance, but with little regard to expected travel times. This too is problematic in that tends to result in false negatives or data aliasing. Simulations from the recently developed efficient hydrologic tracer-test design methodology (EHTD) were compared with those obtained from 32 of the 33 published tracer-

  8. Technical Note: Coupling of chemical processes with the Modular Earth Submodel System (MESSy submodel TRACER

    Directory of Open Access Journals (Sweden)

    P. Jöckel

    2007-11-01

    Full Text Available The implementation of processes related to chemistry into Earth System Models and their coupling within such systems requires the consistent description of the chemical species involved. We provide a tool (written in Fortran95 to structure and manage information about constituents, herein after referred to as tracers, namely the Modular Earth Submodel System (MESSy generic (i.e., infrastructure submodel TRACER. With TRACER it is possible to define a multitude of tracer sets, depending on the spatio-temporal representation (i.e., the grid structure of the model. The required information about a specific chemical species is split into the static meta-information about the characteristics of the species, and its (generally in time and space variable abundance in the corresponding representation. TRACER moreover includes two submodels. One is TRACER_FAMILY, an implementation of the tracer family concept. It distinguishes between two types: type-1 families are usually applied to handle strongly related tracers (e.g., fast equilibrating species for a specific process (e.g., advection. In contrast to this, type-2 families are applied for tagging techniques, in which specific species are artificially decomposed and associated with additional information, in order to conserve the linear relationship between the family and its members. The second submodel is TRACER_PDEF, which corrects and budgets numerical negative overshoots that arise in many process implementations due to the numerical limitations (limited precision, rounding errors. The submodel therefore guarantees the positive definiteness of the tracers and stabilises the integration scheme. As a by-product, it further provides a global tracer mass diagnostic. Last but not least, we present the submodel PTRAC for the definition of prognostic tracers via a Fortran95 namelist. TRACER with its submodels and PTRAC can readily be applied to a variety of models without further requirements. The code and

  9. Fully automated SPE-based synthesis and purification of 2-[{sup 18}F]fluoroethyl-choline for human use

    Energy Technology Data Exchange (ETDEWEB)

    Schmaljohann, Joern [Department of Nuclear Medicine, University of Bonn, Bonn (Germany); Department of Nuclear Medicine, University of Aachen, Aachen (Germany); Schirrmacher, Esther [McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Quebec (Canada); Waengler, Bjoern; Waengler, Carmen [Department of Nuclear Medicine, Ludwig-Maximilians University, Munich (Germany); Schirrmacher, Ralf, E-mail: ralf.schirrmacher@mcgill.c [McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Quebec (Canada); Guhlke, Stefan, E-mail: stefan.guhlke@ukb.uni-bonn.d [Department of Nuclear Medicine, University of Bonn, Bonn (Germany)

    2011-02-15

    Introduction: 2-[{sup 18}F]Fluoroethyl-choline ([{sup 18}F]FECH) is a promising tracer for the detection of prostate cancer as well as brain tumors with positron emission tomography (PET). [{sup 18}F]FECH is actively transported into mammalian cells, becomes phosphorylated by choline kinase and gets incorporated into the cell membrane after being metabolized to phosphatidylcholine. So far, its synthesis is a two-step procedure involving at least one HPLC purification step. To allow a wider dissemination of this tracer, finding a purification method avoiding HPLC is highly desirable and would result in easier accessibility and more reliable production of [{sup 18}F]FECH. Methods: [{sup 18}F]FECH was synthesized by reaction of 2-bromo-1-[{sup 18}F]fluoroethane ([{sup 18}F]BFE) with dimethylaminoethanol (DMAE) in DMSO. We applied a novel and very reliable work-up procedure for the synthesis of [{sup 18}F]BFE. Based on a combination of three different solid-phase cartridges, the purification of [{sup 18}F]BFE from its precursor 2-bromoethyl-4-nitrobenzenesulfonate (BENos) could be achieved without using HPLC. Following the subsequent reaction of the purified [{sup 18}F]BFE with DMAE, the final product [{sup 18}F]FECH was obtained as a sterile solution by passing the crude reaction mixture through a combination of two CM plus cartridges and a sterile filter. The fully automated synthesis was performed using as well a Raytest SynChrom module (Raytest, Germany) or a Scintomics HotboxIII module (Scintomics, Germany). Results: The radiotracer [{sup 18}F]FECH can be synthesized in reliable radiochemical yields (RCY) of 37{+-}5% (Synchrom module) and 33{+-}5% (Hotbox III unit) in less than 1 h using these two fully automated commercially available synthesis units without HPLC involvement for purification. Detailed quality control of the final injectable [{sup 18}F]FECH solution proved the high radiochemical purity and the absence of Kryptofix2.2.2, DMAE and DMSO used in the

  10. HET0016, a selective inhibitor of 20-HETE synthesis, decreases pro-angiogenic factors and inhibits growth of triple negative breast cancer in mice.

    Directory of Open Access Journals (Sweden)

    Thaiz Ferraz Borin

    Full Text Available A selective inhibitor of 20-HETE synthesis, HET0016, has been reported to inhibit angiogenesis. 20-HETE has been known as a second mitogenic messenger of angiogenesis inducing growth factors. HET0016 effects were analyzed on MDA-MB-231 derived breast cancer in mouse and in vitro cell line. MDA-MB-231 tumor cells were implanted in animals' right flank and randomly assigned to early (1 and 2, starting treatments on day 0, or delayed groups (3 and 4 on day 8 after implantation of tumor. Animals received HET0016 (10 mg/kg treatment via intraperitoneal injection for 5 days/week for either 3 or 4 weeks. Control group received vehicle treatment. Tumor sizes were measured on days 7, 14, 21, and 28 and the animals were euthanized on day 22 and 29. Proteins were extracted from the whole tumor and from cells treated with 10 µM HET0016 for 4 and 24 hrs. Protein array kits of 20 different cytokines/factors were used. ELISA was performed to observe the HIF-1α and MMP-2 protein expression. Other markers were confirmed by IHC. HET0016 significantly inhibited tumor growth in all treatment groups at all-time points compared to control (p<0.05. Tumor growth was completely inhibited on three of ten animals on early treatment group. Treatment groups showed significantly lower expression of pro-angiogenic factors compared to control at 21 days; however, there was no significant difference in HIF-1α expression after treatments. Similar results were found in vitro at 24 hrs of HET0016 treatment. After 28 days, significant increase of angiogenin, angiopoietin-1/2, EGF-R and IGF-1 pro-angiogenic factors were found (p<0.05 compared to control, as well as an higher intensity of all factors were found when compared to that of 21 day's data, suggesting a treatment resistance. HET0016 inhibited tumor growth by reducing expression of different set of pro-angiogenic factors; however, a resistance to treatment seemed to happen after 21 days.

  11. A new aquifer assessment tool using reactive tracers

    Science.gov (United States)

    McKnight, D.; Smalley, A. L.; Banwart, S. A.; Lerner, D. N.; Thomson, N. R.; Thornton, S. F.; Wilson, R. D.

    2003-04-01

    A major obstacle to making informed decisions about trigger levels for restoration and choosing remediation options is that current Site Investigation (SI) practice fails to make optimal use of available SI techniques resulting in poor value for money in conceptual site models. Often it is simply too expensive to obtain the type of site data required to build the case for natural attenuation, even though this restoration option may be relatively cheaper than a pump-and-treat system. In particular, aquifer property measurement techniques for groundwater transport and reactions are too costly and this results in over-reliance on literature values or model assumptions. This results in overly uncertain predictions of in situ performance and therefore unnecessarily cautious risk assessment and costly remediation strategies. Therefore, cost-effective SI tools that have the capability of producing high quality characterisation data are required. The dipole flow test which circulates groundwater between isolated injection (source) and extraction (sink) chambers within a single borehole has been used successfully by others to delineate heterogeneous hydraulic properties in both highly permeable and fractured rock aquifers. We propose to extend this approach by adding a suite of reactive tracers into a dipole flow field to assess the geochemical properties and biodegradation potential of aquifers. If successful this will provide a method to ascertain site-specific parameters for use in appropriate reactive transport models. The initial phase of this project involves the construction of a laboratory-scale physical model of a dipole probe to investigate the utility of the dipole flow and reactive tracer test (DFRTT) as an aquifer assessment tool. This phase will also serve as the developmental stage between mathematical theory and a host of planned field trials. The development of the laboratory-scale DFRTT including initial scoping calculations, numerical simulation results

  12. Anthropogenic contaminants as tracers in an urbanizing karst aquifer

    Science.gov (United States)

    Mahler, Barbara; Massei, Nicolas

    2007-04-01

    Karst aquifers are uniquely vulnerable to contamination. In the Barton Springs segment of the karstic Edwards aquifer (Texas, U.S.A.), urban contaminants such as pesticides and volatile organic compounds frequently are detected in spring base flow. To determine whether contaminant concentrations change in response to storms, and if they therefore might act as tracers of focused recharge, samples were collected from Barton Springs at closely spaced intervals following three storms. Two herbicides (atrazine and simazine), two insecticides (carbaryl and diazinon), and a solvent (tetrachloroethene) described breakthrough curves over a 1-week period following one or more storms. The breakthrough curves were decomposed into two to five log-normal subcurves, which were interpreted as representing pulses of contaminants moving through the aquifer. Each subcurve could be used in the same way as an artificial tracer to determine travel time to and recovery at the spring. The contaminants have several advantages over artificial tracers: they represent the actual compounds of interest, they are injected essentially simultaneously at several points, and they are injected under those conditions when transport is of the most interest, i.e., following storms. The response of storm discharge, specific conductance, and contaminant loading at the spring depended on initial aquifer flow conditions, which varied from very low (spring discharge of 0.48 m 3/s) to high (spring discharge of 2.7 m 3/s): concentrations and recovery were the highest when initial aquifer flow conditions were low. This behavior provides information about aquifer structure and the influence of aquifer flow condition on transport properties.

  13. Dual Tracer PET Imaging with FDG and FLT Differentiates Tuberculous Lymphadenopathy from Metastases in a Case of Carcinoma Cervix

    Energy Technology Data Exchange (ETDEWEB)

    Joshi, Prathamesh; Lele, Vikram; Aland, Parag; Gemawat, Shilpa [Jaslok Hospital and Research Centre, Woril (India)

    2013-09-15

    infective/inflammatory pathology was raised in the final report. Considering maximum metabolic activity on FDG PET and feasibility, open biopsy of right axillary lymph node was performed; which revealed tuberculosis. Patient was started on anti-tuberculosis therapy and she reported gradual weight gain with no new symptoms over last 3 months. Though extensively used for evaluation of malignancies, FDG is not a cancer-specific tracer. Non-specific uptake is often seen in active macrophages in infective and inflammatory pathologies. Hence, a tracer that is more specific marker for malignancy can help to identify false-positive FDG PET findings. Use of dual tracer imaging with FDG and FLT to differentiate between benign and malignant lesions has been described in the literature for characterization of pulmonary lesions. FLT is thought to be relatively more specific compared to 18F-FDG, in that it is a cell proliferation tracer; FLT usually does not concentrate in benign lesions. Our case demonstrates the usefulness of a dual tracer imaging approach to identify benign cause of FDG avid lymphadenopathy in a known case of malignancy. This approach may play a vital role.

  14. Does protein intake alter the precursors for synthesis of lactose and non-essential amino acids by the mammary glands of lactating mice?

    Science.gov (United States)

    The aims were to: 1) develop a [U-13C]glucose tracer approach to establish the pathways of and substrates used for milk lactose and casein synthesis in the mouse mammary gland and 2) determine the influence of protein intake on this partition and use for milk synthesis. In Study 1, we determined th...

  15. Environmental radionuclides tracers and timers of terrestrial processes

    CERN Document Server

    Froehlich, Klaus

    2009-01-01

    The book presents a state-of-the-art summary of knowledge on the use of radionuclides to study processes and systems in the continental part of the Earth's environment. It is conceived as a companion to the two volumes of this series, which deal with isotopes as tracers in the marine environment (Livingston, Marine Radioactivity) and with the radioecology of natural and man-made terrestrial systems (Shaw, Radioactivity in Terrestrial Ecosystems). Although the book focuses on natural and anthropogenic radionuclides (radioactive isotopes), it also refers to stable environmental isotopes, which i

  16. Quality assurance and quantitative error analysis by tracer techniques

    Energy Technology Data Exchange (ETDEWEB)

    Schuetze, N.; Hermann, U.

    1983-12-01

    The locations, types and sources of casting defects have been tested by tracer techniques. Certain sites of moulds were labelled using /sup 199/Au, /sup 24/Na sodium carbonate solution, and technetium solution produced in the technetium generator on a /sup 99/Mo//sup 99/Tc elution column. Evaluations were made by means of activity measurements and autoradiography. The locations and causes of casting defects can be determined by error analysis. The surface defects of castings resulting from the moulding materials and from the blacking can be detected by technetium, the subsurface defects are located by gold.

  17. Geotropic tracers in turbulent flows: a proxy for fluid acceleration

    CERN Document Server

    Boffetta, Guido; De Lillo, Filippo; Santamaria, Francesco

    2013-01-01

    We investigate the statistics of orientation of small, neutrally buoyant, spherical tracers whose center of mass is displaced from the geometrical center. If appropriate-sized particles are considered, a linear relation can be derived between the horizontal components of the orientation vector and the same components of acceleration. Direct numerical simulations are carried out, showing that such relation can be used to reconstruct the statistics of acceleration fluctuations up to the order of the gravitational acceleration. Based on such results, we suggest a novel method for the local experimental measurement of accelerations in turbulent flows.

  18. Rebuilding sources of linear tracers after atmospheric concentration concentration

    Directory of Open Access Journals (Sweden)

    J.-P. Issartel

    2003-06-01

    Full Text Available The identification of widespread sources of passive tracers out of atmospheric concentration measurements has become an important challenge of modern meteorology. The paper proposes some mathematical tracks to address this reconstruction of the complex space-time geometry of the sources. The methods are based upon the use of retroplumes. The inverse problem is addressed in a deterministic non statistical frame. The information obtained by local measurements is spread by introducing the concept of illumination. The constraint that the source to be rebuilt is non negative is also addressed. The experimental source ETEX1 is rebuilt in order to evaluate an impulse response of the algorithms.

  19. Flexible tools for interpreting tracer measurements and recent applications

    Science.gov (United States)

    Gusyev, M.; Stewart, M.

    2012-04-01

    Steady increase of groundwater abstraction and nitrate concentrations in groundwater due to agricultural and industrial practices is a major concern for groundwater availability and deterioration of groundwater quality in New Zealand. Studies on groundwater in the Waimea Plains (for example) have shown effects of nitrate input from both diffuse and point sources since 1940. Groundwaters in gravel aquifers under Christchurch have also been studied since 1970 to characterise their flowpaths and recharge sources. In these and other cases, the mixing of waters from different recharge sources following different flow paths can be determined with the use of various tracers and the future course of nitrate concentration in the groundwaters predicted. The input of radionuclides to hydrological systems from nuclear weapons testing in the 1950s and 60s revealed that outflows from such systems often comprise mixtures of water with very wide ranges of ages. Many authors have described methods of deconvolving such outputs with the use of lumped parameter models (LPMs). LPMs are evaluated using specialized software or Excel spreadsheets to compute simulations to measurements of system outputs and therefore estimate parameters of the age distribution. Excel allows easy modification of the code to enable application to individual hydrological features and for a variety of isotopes and chemicals. For the New Zealand studies, Excel spreadsheets with coded Visual Basic functions are used to deduce age distributions based on stable isotope, SF6, CFCs, 3H and 14C data (in order of ages). In particular, 3H is becoming increasingly useful as an age tracer due to the decrease of ambiguity from nuclear testing provided that the measurements can be made with high accuracy (Stewart et al., 2012).These age distributions allow us to derive the input histories of chemicals (e.g. nitrate) and the groundwater recharge sources. In addition, recent developments in modelling groundwater flow and

  20. Union examination of AFP,AFU,AFPL3 and γ-GT in early diagnosis of primary liver cancer

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Objective To explore the significance of union examination of blood serum liver cancer tracers in the early diagnosis of liver cancer. Methods We observed and compared the level of blood serum liver cancer tracers armor embryo protein (AFP),crag algae glycosidase (AFU),armor embryo protein heteroplasmon (AFPL3) and γ-Gu Anxian transferase (γ-GT) in early time for primary liver cancer patients and hepatitis liver cirrhosis patients and those chronic hepatitis B patients who had liver cancer family history. R...

  1. Synthesis of Enantiomerically Pure Anthracyclinones

    Science.gov (United States)

    Achmatowicz, Osman; Szechner, Barbara

    The anthracycline antibiotics are among the most important clinical drugs used in the treatment of human cancer. The search for new agents with improved therapeutic efficacy and reduced cardiotoxicity stimulated considerable efforts in the synthesis of new analogues. Since the biological activity of anthracyclines depends on their natural absolute configuration, various strategies for the synthesis of enantiomerically pure anthracyclinones (aglycones) have been developed. They comprise: resolution of racemic intermediate, incorporation of a chiral fragment derived from natural and non-natural chiral pools, asymmetric synthesis with the use of a chiral auxiliary or a chiral reagent, and enantioselective catalysis. Synthetic advances towards enantiopure anthracyclinones reported over the last 17 years are reviewed.

  2. Sonde for Downhole Measurement of Water Turbidity and Dye Tracer Concentration

    OpenAIRE

    Schnegg, Pierre-André; Bossy, F.

    2005-01-01

    A new flow-through field fluorometer sonde has been designed for use in downhole tracer tests in 2’’ boreholes. The instrument is capable of determining the partial concentration of two dye tracers present simultaneously in the water. In addition, turbidity can be measured if the water is free of tracers. Although the sonde is aimed at boreholed hydrological investigations, it can also be used in surface waters.

  3. Low-cost, High Flexibility I-V Curve Tracer for Photovoltaic Modules

    DEFF Research Database (Denmark)

    Ibirriaga, Julen Joseba Maestro; Pena, Xabier Miquelez de Mendiluce; Opritescu, Adrian

    2010-01-01

    This work presents the design, construction and test of an in-door low cost, high flexibility I-V curve tracer for photovoltaic modules. The tracer is connected to a Xenon lamp based flashing solar simulator. The designed tracer is able to deal with the very fast changing irradiation conditions...... and its control software offers the flexibility to automatically adapt to the different irradiation conditions set by the flashing solar simulator. Simulation and experimental tests have been carried out, in order to verify the behaviour and performance of the designed I-V curve tracer....

  4. Estimation of migration characteristics of a nonsorbing tracer through an artificial rock fracture

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, B. H.; Park, J. K.; Han, P. S. [KAERI, Taejon (Korea, Republic of)

    1998-10-01

    Experiment on the transport of a nonsorbing tracer in an artificial rock fracture was carried out. The scale of an artificial rock was 50x20x5cm. The migration field was assumed as a two dimensional system. Eosine, a kind of an organic dye, was used as a nonsorbing tracer. This tracer was injected as a pulse function in a point source and point withdraw system. Volumetric flow rate was 0.5ml/min. The migration plume of the tracer was captured by a digital camera and compared with a result from transport modeling.

  5. The use of synthetic colloids in tracer transport experiments in saturated rock fractures

    Energy Technology Data Exchange (ETDEWEB)

    Reimus, Paul William [Univ. of California, Berkeley, CA (United States)

    1995-08-01

    Studies of groundwater flow and contaminant transport in saturated, fractured geologic media are of great interest to researchers studying the potential long-term storage of hazardous wastes in or near such media. A popular technique for conducting such studies is to introduce tracers having different chemical and physical properties into a system and then observe the tracers at one or more downstream locations, inferring flow and transport mechanisms from the breakthrough characteristics of the different tracers. Many tracer studies have been conducted in saturated, fractured media to help develop and/or refine models capable of predicting contaminant transport over large scales in such media.

  6. Tracer transport in fractured crystalline rock: Evidence of nondiffusive breakthrough tailing

    Science.gov (United States)

    Becker, M.W.; Shapiro, A.M.

    2000-01-01

    Extended tailing of tracer breakthrough is often observed in pulse injection tracer tests conducted in fractured geologic media. This behavior has been attributed to diffusive exchange of tracer between mobile fluids traveling through channels in fractures and relatively stagnant fluid between fluid channels, along fracture walls, or within the bulk matrix. We present a field example where tracer breakthrough tailing apparently results from nondiffusive transport. Tracer tests were conducted in a fractured crystalline rock using both a convergent and weak dipole injection and pumping scheme. Deuterated water, bromide, and pentafluorobenzoic acid were selected as tracers for their wide range in molecular diffusivity. The late time behavior of the normalized breakthrough curves were consistent for all tracers, even when the pumping rate was changed. The lack of separation between tracers of varying diffusivity indicates that strong breakthrough tailing in fractured geologic media may be caused by advective transport processes. This finding has implications for the interpretation of tracer tests designed to measure matrix diffusion in situ and the prediction of contaminant transport in fractured rock.

  7. Human calcium metabolism including bone resorption measured with {sup 41}Ca tracer

    Energy Technology Data Exchange (ETDEWEB)

    Freeman, S.P.H.T. [Lawrence Livermore National Lab., CA (United States); King, J.C. [California Univ., Berkeley, CA (United States). Dept. of Nutritional Science; Vieira, N.E. [National Inst. of Child Health and Human Development, Bethesda, MD (United States); Woodhouse, L.R. [California Univ., Berkeley, CA (United States). Dept. of Nutritional Science; Yergey, A.L. [National Inst. of Child Health and Human Development, Bethesda, MD (United States)

    1996-08-01

    Accelerator mass spectrometry is so sensitive to small quantities of {sup 41}Ca that it might be used as a tracer in the study of human calcium kinetics to generate unique kinds of data. In contrast with the use of other Ca isotopic tracers, {sup 41}Ca tracer can be so administered that the tracer movements between the various body pools achieve a quasi steady state. Resorbing bone may thus be directly measured. We have tested such a protocol against a conventional stable isotope experiment with good agreement.

  8. AN INTEGRATED APPROACH TO CHARACTERIZING BYPASSED OIL IN HETEROGENEOUS AND FRACTURED RESERVOIRS USING PARTITIONING TRACERS

    Energy Technology Data Exchange (ETDEWEB)

    Akhil Datta-Gupta

    2003-08-01

    We explore the use of efficient streamline-based simulation approaches for modeling partitioning interwell tracer tests in hydrocarbon reservoirs. Specifically, we utilize the unique features of streamline models to develop an efficient approach for interpretation and history matching of field tracer response. A critical aspect here is the underdetermined and highly ill-posed nature of the associated inverse problems. We have adopted an integrated approach whereby we combine data from multiple sources to minimize the uncertainty and non-uniqueness in the interpreted results. For partitioning interwell tracer tests, these are primarily the distribution of reservoir permeability and oil saturation distribution. A novel approach to multiscale data integration using Markov Random Fields (MRF) has been developed to integrate static data sources from the reservoir such as core, well log and 3-D seismic data. We have also explored the use of a finite difference reservoir simulator, UTCHEM, for field-scale design and optimization of partitioning interwell tracer tests. The finite-difference model allows us to include detailed physics associated with reactive tracer transport, particularly those related with transverse and cross-streamline mechanisms. We have investigated the potential use of downhole tracer samplers and also the use of natural tracers for the design of partitioning tracer tests. Finally, the behavior of partitioning tracer tests in fractured reservoirs is investigated using a dual-porosity finite-difference model.

  9. Tracers discrimination of sediment provenience in rural catchment through EDXRF

    Energy Technology Data Exchange (ETDEWEB)

    Melquiades, Fabio L. [Universidade Estadual do Centro Oeste (UNICENTRO), Guarapuava, PR (Brazil). Dept. de Fisica; Thomaz, Edivaldo L. [Universidade Estadual do Centro Oeste (UNICENTRO), Guarapuava, PR (Brazil). Dept. de Geografia

    2010-07-01

    Full text: Sediment dynamics understanding in a drainage system is fundamental for soil and water conservation at hydro graphic basins. This work aim was to discriminate sediment provenance tracers in rural basin. Sediment samples from different points in the headwater (road, forest, riverbank, river sediment deposit) were collected. Energy Dispersive X-ray Fluorescence (EDXRF) was the analytical technique applied, which was efficient to detect the chemical composition of the sediments. The samples were dried for 48h at 50 deg C, ground and sieved for granulometry 1mm. In natura samples (3 g) were placed in cells covered with mylar film for irradiation. Titanium, Mn, Fe, Cu, Zn, Y and Zr were identified. It was concluded that the elements, when analyzed individually or paired, do not allow a clear environment distinction except for yttrium (Y) that indicates distinct characteristics between the riverbank materials related to the other environments. However, the cluster analysis provided discrimination between the different sources of sediment. Also, it was verified that the recent deposited sediment in the river channel displays greater similarity with the materials of the road than with the riverbank. It is probable that the roads has been the mainly sediment source in the studied headwater. The methodology is innovative for tracer determination in soil and erosion quantification. (author)

  10. Accurate blood flow measurements: are artificial tracers necessary?

    Directory of Open Access Journals (Sweden)

    Christian Poelma

    Full Text Available Imaging-based blood flow measurement techniques, such as particle image velocimetry, have become an important tool in cardiovascular research. They provide quantitative information about blood flow, which benefits applications ranging from developmental biology to tumor perfusion studies. Studies using these methods can be classified based on whether they use artificial tracers or red blood cells to visualize the fluid motion. We here present the first direct comparison in vivo of both methods. For high magnification cases, the experiments using red blood cells strongly underestimate the flow (up to 50% in the present case, as compared to the tracer results. For medium magnification cases, the results from both methods are indistinguishable as they give the same underestimation of the real velocities (approximately 33%, based on in vitro reference measurements. These results suggest that flow characteristics reported in literature cannot be compared without a careful evaluation of the imaging characteristics. A method to predict the expected flow averaging behavior for a particular facility is presented.

  11. Isotopologues of dense gas tracers in NGC 1068

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Junzhi; Qiu, Jianjie [Shanghai Astronomical Observatory, Chinese Academy of Sciences, 80 Nandan Road, 200030, Shanghai (China); Zhang, Zhi-Yu [Institute for Astronomy, University of Edinburgh, Royal Observatory, Blackford Hill, Edinburgh EH9 3HJ (United Kingdom); Shi, Yong [School of Astronomy and Space Science, Nanjing University, Nanjing, 210093 (China); Zhang, Jiangshui [Center For Astrophysics, GuangZhou University, 510006, GuangZhou (China); Fang, Min, E-mail: jzwang@shao.ac.cn [ESO, Karl Schwarzschild Strasse 2, D-85748 Garching bei Munich (Germany)

    2014-11-20

    We present observations of isotopic lines of dense gas tracers toward the nuclear region of nearby Seyfert 2 galaxy NGC 1068 with the IRAM 30 m telescope and the Atacama Pathfinder Experiment (APEX) 12 m telescope. We detected four isotopic lines (H{sup 13}CN 1-0, H{sup 13}CO{sup +} 1-0, HN{sup 13}C 1-0, and HC{sup 18}O{sup +} 1-0) at the 3 mm band with the IRAM 30 m telescope and obtained upper limits of other lines. We calculated optical depths of dense gas tracers with the detected isotopic lines of HCN 1-0, HCO{sup +} 1-0, and HNC 1-0. We find that the {sup 14}N/{sup 15}N abundance ratio is greater than 420 if we adopt the upper limit of HC{sup 15}N(1-0) emission. Combining this with fluxes of 1-0 lines from IRAM 30 m observations and the upper limit of 3-2 lines from APEX 12 m observations, we also estimated the excitation condition of molecular gas in the nuclear region of NGC 1068, which is less dense than that in the extreme starburst regions of galaxies.

  12. Titan's post-equinox circulation revealed using chemical tracers

    Science.gov (United States)

    Teanby, N. A.; Irwin, P. G. J.; Nixon, C. A.; de Kok, R.; Vinatier, S.; Coustenis, A.; Calcutt, S. B.

    2012-04-01

    Titan’s atmosphere harbors a vast array of minor chemical compounds produced by its active photochemical cycle - including many hydrocarbon and nitrile species. These species have a wide range of lifetimes and can be used as chemical tracers of atmospheric motion on a variety of time scales (Teanby et al 2008). Therefore, by measuring how the abundances of these species vary during Cassini’s mission so far, it is possible to probe changes in Titan’s general circulation. Here we use eight years of Cassini Composite InfraRed Spectrometer (CIRS) data to study how the atmospheric circulation behaves during the equinox and post-equinox periods. As northern winter progressed to northern spring, significant changes in the distribution of trace gases were observed. These include an increase in trace gas abundance at the north pole and northward migration of the vortex boundary. The implications of the observed changed will be discussed - including a possible interpretation of the recent changes as a weakening of the north polar vortex accompanied by a reduction in cross-vortex mixing. References: Teanby, N. A., et al. (2008) "Titan's winter polar vortex structure revealed by chemical tracers". JGR-Planets, Vol. 113, E12003. Figure showing the observed variations in temperature and composition from the mission so far.

  13. Inversion of Hydrological Tracer Test Data Using TomogrpahicConstraints

    Energy Technology Data Exchange (ETDEWEB)

    Linde, Niklas; Finsterle, Stefan; Hubbard, Susan

    2004-11-11

    A reasonable description of the hydraulic conductivity structure is a prerequisite for modeling contaminant transport. However, formulations of hydrogeological inverse problems utilizing hydrogeological data only often fail to reliably resolve features at a resolution required for accurately predicting transport. Incorporation of geophysical data into the inverse problem offers the potential to increase this resolution. In this study, we invert hydrological tracer test data using the shape and relative magnitude variations derived from geophysical tomographic data to regionalize a hydrogeological inverse problem in order to estimate the hydraulic conductivity structure. Our approach does not require that the petrophysical relationship be known a-priori, but that it is linear and stationary within each geophysical anomaly. However, tomograms are imperfect models of geophysical properties and geophysical properties are not necessarily strongly linked to hydraulic conductivity. Therefore, we focus on synthetic examples where the correlation between radar velocity and hydraulic conductivity, as well as the geophysical data acquisition errors, are varied in order to assess what aspects of the hydraulic conductivity structure we can expect to resolve under different conditions. The results indicate that regularization of the tracer inversion procedure using geophysical data improves estimates of hydraulic conductivity. We find that even under conditions of corrupted geophysical data, we can accurately estimate the effective hydraulic conductivity and areas of high and low hydraulic conductivity. However, given imperfect geophysical data, our results suggest that we cannot expect accurate estimates of the variability of the hydraulic conductivity structure.

  14. Accurate blood flow measurements: are artificial tracers necessary?

    Science.gov (United States)

    Poelma, Christian; Kloosterman, Astrid; Hierck, Beerend P; Westerweel, Jerry

    2012-01-01

    Imaging-based blood flow measurement techniques, such as particle image velocimetry, have become an important tool in cardiovascular research. They provide quantitative information about blood flow, which benefits applications ranging from developmental biology to tumor perfusion studies. Studies using these methods can be classified based on whether they use artificial tracers or red blood cells to visualize the fluid motion. We here present the first direct comparison in vivo of both methods. For high magnification cases, the experiments using red blood cells strongly underestimate the flow (up to 50% in the present case), as compared to the tracer results. For medium magnification cases, the results from both methods are indistinguishable as they give the same underestimation of the real velocities (approximately 33%, based on in vitro reference measurements). These results suggest that flow characteristics reported in literature cannot be compared without a careful evaluation of the imaging characteristics. A method to predict the expected flow averaging behavior for a particular facility is presented.

  15. Artificial sweeteners as potential tracers in groundwater in urban environments

    Science.gov (United States)

    Van Stempvoort, Dale R.; Roy, James W.; Brown, Susan J.; Bickerton, Greg

    2011-04-01

    SummaryThere is little information available on the prevalence of artificial sweeteners in groundwater, though these compounds may prove to be useful tracers of human wastewater, especially in urban settings with complex hydrology. In this study, the artificial sweetener acesulfame was detected in groundwater at all eight urban sites investigated (from five different urban areas in Canada), often at high concentrations (i.e., μg/L-scale). In a municipal wastewater plume at Jasper, Alberta, acesulfame was strongly correlated with chloride and was positively correlated with other wastewater-related contaminants indicating that this sweetener has potential to be a good tracer of young wastewater (artificial sweeteners were detected in urban groundwater: saccharin at six of the sites, sucralose at three sites, and cyclamate at five of seven sites where it was analyzed. The occurrence of sucralose may have been affected by its detection limit, which was much higher than for the other sweeteners. These results, and those of a parallel study, are the first reported detections of saccharin and cyclamate in groundwater, and suggest that these sweeteners may be more common than previously anticipated. In general, fewer samples from each site contained these other three sweeteners compared to acesulfame. At Barrie, Ontario, adjacent to an old landfill, the concentration of saccharin was higher than acesulfame in many samples. These results suggest that analyses of multiple sweeteners, rather than just acesulfame, may provide useful information on contaminant sources and groundwater conditions in urban settings. Further work is needed to address this potential use.

  16. Acupuncture meridians demythified. A study using the radioactive tracer method

    Energy Technology Data Exchange (ETDEWEB)

    Simon, J.; Esquerre, J.P.; Guiraud, R.; Guiraud, G.; Lazorthes, Y.

    1988-07-01

    Radioactive trajectories can be visualized by injecting a radioactive tracer, technetium 99 m, at the site of acupuncture points. To determine the exact nature of these trajectories we performed several experiments on healthy volunteers, and our results may be summarized as follows. The target organs of technetium 99 m, and notably the thyroid gland, were always visualized. The circulating radioactivity, visible on scintiscans and confirmed by venous blood counts, was not negligible. The radioactive trajectories we observed were often divided at their starting point and did not extend along the whole length of the acupuncture meridians they might have made visible. The radioactive trajectories disappeared after venous blockade to reappear when the blockade was lifted. Finally, the radioactive trajectories obtained were very similar after injection at the acupuncture point and at a control point. These findings indicate a lymphatic and venous drainage of the radioactive tracer at the site of injection followed by transportation through the veins, rather than visualization of acupuncture meridians as suggested by some authors.

  17. Using biofuel tracers to study alternative combustion regimes

    Science.gov (United States)

    Mack, J. H.; Flowers, D. L.; Buchholz, B. A.; Dibble, R. W.

    2007-06-01

    Interest in the use of alternative fuels and engines is increasing as the price of petroleum climbs. The inherently higher efficiency of Diesel engines has led to increased adoption of Diesels in Europe, capturing approximately 40% of the new passenger car market. Unfortunately, lower CO2 emissions are countered with higher nitrogen oxides (NOx) and particulate matter (PM) emissions and higher noise. Adding oxygenated compounds to the fuel helps reduce PM emissions. However, relying on fuel alone to reduce PM is unrealistic due to economic constraints and difficult due to the emerging PM standards. Keeping peak combustion temperature below 1700 K inhibits NOx formation. Altering the combustion regime to burn at temperatures below the NOx threshold and accept a wide variety of fuels seems like a promising alternative for future engines. Homogeneous charge compression ignition (HCCI) is a possible solution. Fuel and air are well mixed prior to intake into a cylinder (homogeneous charge) and ignition occurs by compression of the fuel-air mixture by the piston. HCCI is rapid and relatively cool, producing little NOx and PM. Unfortunately, it is hard to control since HCCI is initiated by temperature and pressure instead of a spark or direct fuel injection. We investigate biofuel HCCI combustion, and use intrinsically labeled biofuels as tracers of HCCI combustion. Data from tracer experiments are used to improve our combustion modeling.

  18. Single well tracer method to evaluate enhanced recovery

    Science.gov (United States)

    Sheely, Jr., Clyde Q.; Baldwin, Jr., David E.

    1978-01-01

    Data useful to evaluate the effectiveness of or to design an enhanced recovery process (the recovery process involving mobilizing and moving hydrocarbons through a hydrocarbon-bearing subterranean formation from an injection well to a production well by injecting a mobilizing fluid into the injection well) are obtained by a process which comprises sequentially: determining hydrocarbon saturation in the formation in a volume in the formation near a well bore penetrating the formation, injecting sufficient of the mobilizing fluid to mobilize and move hydrocarbons from a volume in the formation near the well bore penetrating the formation, and determining by the single well tracer method a hydrocarbon saturation profile in a volume from which hydrocarbons are moved. The single well tracer method employed is disclosed by U.S. Pat. No. 3,623,842. The process is useful to evaluate surfactant floods, water floods, polymer floods, CO.sub.2 floods, caustic floods, micellar floods, and the like in the reservoir in much less time at greatly reduced costs, compared to conventional multi-well pilot test.

  19. CH as a Molecular Gas Tracer and C-shock Tracer Across a Molecular Cloud Boundary in Taurus

    Science.gov (United States)

    Xu, Duo; Li, Di

    2016-12-01

    We present new observations of all three ground-state transitions of the methylidyne (CH) radical and all four ground-state transitions of the hydroxyl (OH) radical toward a sharp boundary region of the Taurus molecular cloud. These data were analyzed in conjunction with existing CO and dust images. The derived CH abundance is consistent with previous observations of translucent clouds (0.8 ≤ A v ≤ 2.1 mag). The X(CH)-factor is nearly a constant (1.0 ± 0.06) × 1022 cm-2 K-1 km-1 s in this extinction range, with less dispersion than that of the more widely used molecular tracers CO and OH. CH turns out be a better tracer of total column density in such an intermediate extinction range than CO or OH. Compared with previous observations, CH is overabundant below 1 mag extinction. Such an overabundance of CH is consistent with the presence of a C-shock. CH has two kinematic components, one of which shifts from 5.3 to 6 km s-1, while the other stays at 6.8 km s-1 when moving from outside toward inside of the cloud. These velocity behaviors exactly match previous OH observation. The shifting of the two kinematic components indicates colliding streams or gas flow at the boundary region, which could be the cause of the C-shock.

  20. New radioiodinated carboxylic and hydroxamic matrix metalloproteinase inhibitor tracers as potential tumor imaging agents

    Energy Technology Data Exchange (ETDEWEB)

    Oltenfreiter, Ruth E-mail: ruth.oltenfreiter@rug.ac.be; Staelens, Ludovicus; Lejeune, Annabelle; Dumont, Filip; Frankenne, Francis; Foidart, Jean-Michel; Slegers, Guido

    2004-05-01

    Several studies have demonstrated a positive correlation between tumor progression and expression of extracellular proteinases such as matrix metalloproteinases (MMPs). MMP-2 and MMP-9 have become attractive targets for cancer research because of their increased expression in human malignant tumor tissues of various organs, providing a target for medical imaging techniques. Radioiodinated carboxylic and hydroxamic MMP inhibitors 2-(4'-[{sup 123}I]iodo-biphenyl-4-sulfonylamino)-3-(1H-indol-3-yl)-propionic acid (9) and 2-(4'-[{sup 123}I]iodo-biphenyl-4-sulfonylamino)-3-(1H-indol-3-yl)-propionamide (11) were synthesized by electrophilic aromatic substitution of the tributylstannyl derivatives and resulted in radiochemical yields of 60% {+-} 5% (n = 3) and 70% {+-} 5% (n = 6), respectively. In vitro zymography and enzyme assays showed high inhibition capacities of the inhibitors on gelatinases. In vivo biodistribution showed no long-term accumulation in organs and the possibility to accumulate in the tumor. These results warrant further studies of radioiodinated carboxylic and hydroxamic MMP inhibitor tracers as potential SPECT tumor imaging agents.

  1. Technical Note: Coupling of chemical processes with the Modular Earth Submodel System (MESSy submodel TRACER

    Directory of Open Access Journals (Sweden)

    R. Sander

    2008-03-01

    Full Text Available The implementation of processes related to chemistry into Earth System Models and their coupling within such systems requires the consistent description of the chemical species involved. We provide a tool (written in Fortran95 to structure and manage information about constituents, hereinafter referred to as tracers, namely the Modular Earth Submodel System (MESSy generic (i.e., infrastructure submodel TRACER. With TRACER it is possible to define a multitude of tracer sets, depending on the spatio-temporal representation (i.e., the grid structure of the model. The required information about a specific chemical species is split into the static meta-information about the characteristics of the species, and its (generally in time and space variable abundance in the corresponding representation. TRACER moreover includes two submodels. One is TRACER_FAMILY, an implementation of the tracer family concept. It distinguishes between two types: type-1 families are usually applied to handle strongly related tracers (e.g., fast equilibrating species for a specific process (e.g., advection. In contrast to this, type-2 families are applied for tagging techniques. Tagging means the artificial decomposition of one or more species into parts, which are additionally labelled (e.g., by the region of their primary emission and then processed as the species itself. The type-2 family concept is designed to conserve the linear relationship between the family and its members. The second submodel is TRACER_PDEF, which corrects and budgets numerical negative overshoots that arise in many process implementations due to the numerical limitations (e.g., rounding errors. The submodel therefore guarantees the positive definiteness of the tracers and stabilises the integration scheme. As a by-product, it further provides a global tracer mass diagnostic. Last but not least, we present the submodel PTRAC, which allows the definition of tracers via a Fortran95 namelist, as a

  2. Tracer tests - possibilities and limitations. Experience from SKB fieldwork: 1977-2007

    Energy Technology Data Exchange (ETDEWEB)

    Loefgren, Martin; Crawford, James; Elert, Mark (Kemakta Konsult AB, Stockholm (SE))

    2007-09-15

    Tracer tests have played, and still play, a central role in investigations relating to the understanding of radionuclide retention processes in the field. At present there is a debate within the scientific community concerning how, and to what extent, tracer tests can be used to evaluate large-scale and long-term transport and retardation of radionuclides and other solutes of interest for Safety Assessment of repositories for spent nuclear fuel. In this report the SKB fieldwork on tracer tests performed at Swedish sites from 1977 to 2007 is described and discussed. Furthermore, the knowledge and process understanding evolved during the decades of radionuclide transport experiments and modelling within the SKB programme is summarised. One of the main objectives of this report is to discuss what data and knowledge can be extracted from different in situ tests in a robust fashion. Given the level of complexity associated with transport processes that may occur over the timescale of a tracer test, the utility of tracer tests is considered in the context of evidence-based interpretations of data which we characterise in the form of a sequence of questions of increasing complexity. The complexity of this sequence ranges from whether connection can be confirmed between injection and withdrawal points to whether quantitative data can be extrapolated from a tracer test to be subsequently used in Safety Assessment. The main findings of this report are that: Field scale tracer tests can confirm flow connectivity. Field scale tracer tests confirm the existence of retention. Field scale tracer tests alone can only broadly substantiate our process understanding. However, if performing extensive Site Characterisation and integrating the tracer test results with the full range of geoscientific information available, much support can be given to our process understanding. Field scale tracer tests can deliver the product of the material property group MPG and the F-factor, valid

  3. Simultaneous Analyses and Applications of Multiple Fluorobenzoate and Halide Tracers in Hydrologic Studies

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Q; Moran, J E

    2004-01-22

    An analytical method that employs ion chromatography has been developed to more fully exploit the use of fluorobenzoic acids (FBAs) and halides as hydrologic tracers. In a single run, this reliable, sensitive, and robust method can simultaneously separate and quantify halides (fluoride, chloride, bromide, and iodide) and up to seven FBAs from other common groundwater constituents (e.g., nitrate and sulfate). The usefulness of this ion chromatographic (IC) analytical method is demonstrated in both field and laboratory tracer experiments. Field experiments in unsaturated tuff featuring fractures or a fault show that this efficient and cost-effective method helps achieve the objectives of tracer studies that use multiple FBAs and/or diffusivity tracers (simultaneous use of one or more FBA and halide). The field study examines the hydrologic response of fractures and the matrix to different flow rates and the contribution of matrix diffusion in chemical transport. Laboratory tracer experiments with eight geologic media from across the United States--mostly from Department of Energy facilities where groundwater contamination is prevalent and where subsurface characterization employing tracers has been ongoing or is in need--reveal several insights about tracer transport behavior: (1) Bromide and FBAs are not always transported conservatively. (2) The delayed transport of these anionic tracers is likely related to geologic media characteristics, such as organic matter, pH, iron oxide content, and clay mineralogy. (3) Any use of iodine as a hydrologic tracer should take into account the different sorption behaviors of iodide and iodate and the possible conversion of iodine's initial chemical form. (4) The transport behavior of potential FBA and halide tracers under relevant geochemical conditions should be evaluated before beginning ambitious, large-scale field tracer experiments.

  4. Synthesis and evaluation of radioiodinated cyclooxygenase-2 inhibitors as potential SPECT tracers for cyclooxygenase-2 expression

    Energy Technology Data Exchange (ETDEWEB)

    Kuge, Yuji [Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501 (Japan)]. E-mail: kuge@pharm.kyoto-u.ac.jp; Katada, Yumiko [Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501 (Japan); Shimonaka, Sayaka [Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501 (Japan); Temma, Takashi [Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501 (Japan); Kimura, Hiroyuki [Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501 (Japan); Kiyono, Yasushi [Radioisotopes Research Laboratory, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Kyoto 606-8507 (Japan); Yokota, Chiaki [Cerebrovascular Laboratory, National Cardiovascular Center Research Institute, Osaka 565-8565 (Japan); Minematsu, Kazuo [Cerebrovascular Division, Department of Medicine, National Cardiovascular Center Research Institute, Osaka 565-8565 (Japan); Seki, Koh-ichi [Central Institute of Isotope Science, Hokkaido University, Hokkaido 060-8638 (Japan); Tamaki, Nagara [Department of Nuclear Medicine, Graduate School of Medicine, Hokkaido University, Hokkaido 060-8638 (Japan); Ohkura, Kazue [Department of Radiopharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Hokkaido 061-0293 (Japan); Saji, Hideo [Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501 (Japan)

    2006-01-15

    Although several COX-2 inhibitors have recently been radiolabeled, their potential for imaging COX-2 expression remains unclear. In particular, the sulfonamide moiety of COX-2 inhibitors may cause slow blood clearance of the radiotracer, due to its affinity for carbonic anhydrase (Canada) in erythrocytes. Thus, we designed a methyl sulfone-type analogue, 5-(4-iodophenyl)-1-[4-(methylsulfonyl)phenyl]-3-trifluoromethyl-1H-pyrazole (IMTP). In this study, the potential of radioiodinated IMTP was assessed in comparison with a {sup 125}I-labeled celecoxib analogue with a sulfonamide moiety ({sup 125}I-IATP). Methods: The COX inhibitory potency was assessed by measuring COX-catalyzed oxidation by hydrogen peroxide. The biodistribution of {sup 125}I-IMTP and {sup 125}I-IATP was determined by the ex vivo tissue counting method in rats. Distribution of the labeled compounds to rat blood cells was measured. Results: The COX-2 inhibitory potency of IMTP (IC{sub 5}=5.16 {mu}M) and IATP (IC{sub 5}=8.20 {mu}M) was higher than that of meloxicam (IC{sub 5}=29.0 {mu}M) and comparable to that of SC-58125 (IC{sub 5}=1.36 {mu}M). The IC{sub 5} ratios (COX-1/COX-2) indicated the high isoform selectivity of IMTP and IATP for COX-2. Significant levels of {sup 125}I-IMTP and {sup 125}I-IATP were observed in the kidneys and the brain (organs known to express COX-2). The blood clearance of {sup 125}I-IMTP was much faster than that of {sup 125}I-IATP. Distribution of {sup 125}I-IATP to blood cells (88.0%) was markedly higher than that of {sup 125}I-IMTP (18.1%), which was decreased by CA inhibitors. Conclusions: Our results showed a high inhibitory potency and selectivity of IMTP for COX-2. The substitution of a sulfonamide moiety to a methyl sulfone moiety effectively improved the blood clearance of the compound, indicating the loss of the cross reactivity with CA in {sup 125}I-IMTP. {sup 123}I-IMTP may be a potential SPECT radiopharmaceutical for COX-2 expression.

  5. ATTILA - Atmospheric Tracer Transport In a Langrangian Model

    Energy Technology Data Exchange (ETDEWEB)

    Reithmeier, C.; Sausen, R.

    2000-07-01

    The Lagrangian model ATTILA (atmospheric tracer transport in a Lagrangian model) has been developed to treat the global-scale transport of passive trace species in the atmosphere within the framework of a general circulation model (GCM). ATTILA runs online within the GCM ECHAM4 and uses the GCM produced wind field to advect the centrois of 80.000 to 180.000 constant mass air parcels into which the model atmosphere is divided. Each trace constituent is thereby represented by a mass mixing ratio in each parcel. ATTILA contains state-of-the-art parameterizations of convection, turbulent boundary layer mixing, and interparcel transport and provides an algorithm to map the tracer concentrations from the trajectories to the ECHAM model grid. We use two experiments to evaluate the transport characteristics of ATTILA against observations and the standard semiLagrangian transport scheme of ECHAM. In the first experiment we simulate the distribution of the short-lived tracer Radon ({sup 222}Rn) in order to examine fast vertical transport over continents, and long-range transport from the continents to remote areas. In the second experiment, we simulate the distribution of radiocarbon ({sup 14}C) that was injected into the northern stratosphere during the nuclear weapon tests in the early 60ties, in order to examine upper tropospheric and stratospheric transport characteristics. ATTILA compares well to the observations and in many respects to the semiLagrangian scheme. However, contrary to the semiLagrangian scheme, ATTILA shows a greatly reduced meridional transport in the upper troposphere and lower stratosphere, and a reduced downward flux from the stratosphere to the troposphere, especially in midlatitudes. Since both transport schemes use the same model meteorology, we conclude that the often cited enhanced meridional transport and overestimated downward flux in ECHAM as described above is rather due to the numerical properties of the semiLagrangian scheme than due to an

  6. Regional Groundwater Processes and Flow Dynamics from Age Tracer Data

    Science.gov (United States)

    Morgenstern, Uwe; Stewart, Mike K.; Matthews, Abby

    2016-04-01

    Age tracers are now used in New Zealand on regional scales for quantifying the impact and lag time of land use and climate change on the quantity and quality of available groundwater resources within the framework of the National Policy Statement for Freshwater Management 2014. Age tracers provide measurable information on the dynamics of groundwater systems and reaction rates (e.g. denitrification), essential for conceptualising the regional groundwater - surface water system and informing the development of land use and groundwater flow and transport models. In the Horizons Region of New Zealand, around 200 wells have tracer data available, including tritium, SF6, CFCs, 2H, 18O, Ar, N2, CH4 and radon. Well depths range from shallower wells in gravel aquifers in the Horowhenua and Tararua districts, and deeper wells in the aquifers between Palmerston North and Wanganui. Most of the groundwater samples around and north of the Manawatu River west of the Tararua ranges are extremely old (>100 years), even from relatively shallow wells, indicating that these groundwaters are relatively disconnected from fresh surface recharge. The groundwater wells in the Horowhenua tap into a considerably younger groundwater reservoir with groundwater mean residence time (MRT) of 10 - 40 years. Groundwater along the eastern side of the Tararua and Ruahine ranges is significantly younger, typically groundwater recharge rates, as deduced from groundwater depth and MRT, are extremely low in the central coastal area, consistent with confined groundwater systems, or with upwelling of old groundwater close to the coast. Very low vertical recharge rates along the Manawatu River west of the Manawatu Gorge indicate upwelling groundwater conditions in this area, implying groundwater discharge into the river is more likely here than loss of river water into the groundwater system. High recharge rates observed at several wells in the Horowhenua area and in the area east of the Tararua and

  7. Studies on the preparation of low-carrier Se-73,75 tracers for in vivo examinations; Untersuchungen zur Darstellung traegerarm 73,75Se-markierter Tracer fuer in vivo Untersuchungen

    Energy Technology Data Exchange (ETDEWEB)

    Helfer, Andreas

    2013-04-03

    With the growing importance of positron emission tomography (PET) for in vivo imaging in diagnostic medicine there is great interest of developing new labelling methods for the positron emitter selenium-73. As attractive application an examination of a no-carrier-added (n.c.a.) preparation of the analogous tracer Sulindac Selenid and of the selenium containing compound Ebselen was examined with {sup 73,75}Se. First of all a labelling strategy for Sulindac Selenid based on a protected precursor was developed. This precursor should further be transformed into the corresponding standard compound for chomatographic identification of the n.c.a. product. This, however, was not possible. An alternative synthesis method also did not result in a product. Thus, a radioactive labelling in case of Sulindac Selenid was not indicated in spite of a successful synthesis of a precursor. The preparation of Ebselen was performed as earlier described by a sequential one-pot synthesis with a yield of 46 %. An adaption of the reaction parameters to a radiosynthesis with {sup 75}Se failed on the n.c.a. state and also after adding carrier to the reaction mixture. The desired product could, however, be prepared in a copper catalysed one-pot radiosynthesis for the first time under carrier-added conditions. Here, optimized conditions resulted in radiochemical yields of 60 ± 18 %. A no-carrier-added product could finally be achieved using sulphur as nonisotopic carrier in the reaction mixture. After optimisation of reaction parameters n.c.a. [{sup 75}Se]Ebselen could be synthesized with radiochemical yields of 55 ± 7 % within 4 h. Furthermore the desired product could be separated by RHPL-chromatography from its co-produced sulfur-analogue. After transferring the conditions to radiosyntheses with the positron emitter {sup 73}Se, n.c.a. [{sup 73}Se]Ebselen could be achieved with a radiochemical yield of 22 ± 1 % and can now be used as a potential radiotracer in preclinical evaluation

  8. Tracer-/Heat transfer decoupling in a heterogenous, fault zone based hydrothermal reservoir in the Upper Rhine Basin; Tracer-/Waermetrnasportentkopplung in einem heterogenen, stoerungszonengepraegten Hydrothermalreservoir im Oberrheingraben

    Energy Technology Data Exchange (ETDEWEB)

    Ghergut, I.; Licha, T.; Maier, F.; Nottebohm, M.; Sauter, M. [Goettingen Univ. (Germany). Abt. Angewandte Geologie; Meixner, J.; Rettenmaier, D. [Karlsruher Institut fuer Technologie (KIT) (Germany). Abt. Hydrogeologie

    2012-10-16

    Heat transport processes and tracer transport processes probe the boundaries of a tracer based prognosis of the thermal lifetime for a geothermal borehole doublet in a heterogeneous hydrothermal reservoir in the Upper Rhine Basin whose behaviour is characterized by two or three large-scale not bored fault zones. A hydro-geologic structure model of the reservoir is the fundament for the identification of decisive fluid transport processes. The thermal breakdown is a rather abstract threatening with a large time distance for the geothermal borehole doublet. Nearby dangers of hydro-geochemical and hydro-mechanical nature require tracer tests for their quantification. Long dwell times are expected in a circulation test, while interpretation difficulties are expected in early tracer signals. Heat-push-shut-in tests or tracer-push-flowback tests at the geothermal re-injection drilling can supply information on transport effective aquifer parameters in an even more appropriate time. A fluid transport based characterization of the fault zones is only imaginable by means of long-term circulation tests with conservative and thermo-sensitive tracers.

  9. Rapid and simple determination of delivery after iontophoretic and pressure injections of radiolabeled tracer substances

    Energy Technology Data Exchange (ETDEWEB)

    Imai, H.; Steindler, D.A.; Kitai, S.T. (Michigan State Univ., East Lansing (USA))

    1983-04-01

    A fluorographic method is described using X-ray film analysis for the determination of delivery of radiolabeled tracer substances both in Agar plates and in tissue sections. This method is most useful in neuroanatomical autoradiographic studies for providing rapid identification of delivery, placement and extent of an injection site after iontophoresis or pressure injections of radiolabeled axonal tracer substances.

  10. Borehole flowmeter logging for the accurate design and analysis of tracer tests.

    Science.gov (United States)

    Basiricò, Stefano; Crosta, Giovanni B; Frattini, Paolo; Villa, Alberto; Godio, Alberto

    2015-04-01

    Tracer tests often give ambiguous interpretations that may be due to the erroneous location of sampling points and/or the lack of flow rate measurements through the sampler. To obtain more reliable tracer test results, we propose a methodology that optimizes the design and analysis of tracer tests in a cross borehole mode by using vertical borehole flow rate measurements. Experiments using this approach, herein defined as the Bh-flow tracer test, have been performed by implementing three sequential steps: (1) single-hole flowmeter test, (2) cross-hole flowmeter test, and (3) tracer test. At the experimental site, core logging, pumping tests, and static water-level measurements were previously carried out to determine stratigraphy, fracture characteristics, and bulk hydraulic conductivity. Single-hole flowmeter testing makes it possible to detect the presence of vertical flows as well as inflow and outflow zones, whereas cross-hole flowmeter testing detects the presence of connections along sets of flow conduits or discontinuities intercepted by boreholes. Finally, the specific pathways and rates of groundwater flow through selected flowpaths are determined by tracer testing. We conclude that the combined use of single and cross-borehole flowmeter tests is fundamental to the formulation of the tracer test strategy and interpretation of the tracer test results.

  11. PENGEMBANGAN SISTEM TRACER STUDY ONLINE BERBASIS WEBSITE DI STMIK AMIKOM YOGYAKARTA

    Directory of Open Access Journals (Sweden)

    Alfie Nur Rahmi

    2014-06-01

    Full Text Available Tracer study is a mechanism that is performed by various parties to keep track of alumni in order to measure the relevance of the purpose and process of education with the current condition of the alumni. In addition, the results of a tracer study was also used as a condition of completeness of accreditation by Badan Akreditasi Nasional Perguruan Tinggi (BAN - PT . Tracer studies can be done in 2 ways , namely tracer manually and online. STMIK AMIKOM Yogyakarta is one of the colleges that have done online with tracer studies utilizing tracer system online at the alumni web pages since 2010. Yet in reality, the system utilization online tracer deemed not optimal in terms of both alumni and the AMIKOM . Based on the analysis of the old system using PIECES analysis, showed some problems and flaws in the old system . The results of this study are expected to prototype a new system able to answer the problems and deficiencies in the old system so that it can optimize the function and use of the online tracer system by the alumni and the AMIKOM.

  12. Influence of Dispersion on Transport of Tracer through Unsaturated Porous Media

    Directory of Open Access Journals (Sweden)

    T Bunsri

    2008-01-01

    Full Text Available The dispersion phenomenon has resulted from the various water flow magnitude and direction in porous media. The dissolved tracer tends to spread due to dispersion and then travel time of tracer through the porous media increases. In unsaturated porous media, dispersion coefficient varies with non-linear Darcy’s velocity and the water content. These effects observed in both of the laboratory scale sand and soil columns (20 cm. The unsaturated infiltration column and tracer tests have been used to interpret the relationships between Darcy’s velocity and the water content together with the dispersion coefficient. However, the dispersivity coefficient cannot be measured directly, it has to determine from advection-dispersion equation (ADE, which can be used to model the tracer transport in unsaturated porous media. The model was used to describe the non-linear functions of water contents and dispersivities for both porous media. The simulations have been verified that the dispersion of tracer through soil is higher than sand column and also travel time of tracer through soil is longer than sand column. Even though, soil has very low degree of pore velocity, the high dispersivity is observed in the simulations. The water content and tracer concentration profiles reveal that the increase of dispersivity induces the increase of flow path distance and the decrease of pore velocity. The maximum dispersivity was observed when the water content of porous media is relatively low; this leads the maximum of spreading of tracer.

  13. Tracer Gas Technique Versus a Control Box Method for Estimating Direct Capture Efficiency of Exhaust Systems

    DEFF Research Database (Denmark)

    Madsen, U.; Aubertin, G.; Breum, N. O.;

    Numerical modelling of direct capture efficiency of a local exhaust is used to compare the tracer gas technique of a proposed CEN standard against a more consistent approach based on an imaginary control box. It is concluded that the tracer gas technique is useful for field applications....

  14. Data summary of 1985 SF sub 6 tracer experiments at Andorra (Teruel) power plant

    Energy Technology Data Exchange (ETDEWEB)

    Sivertsen, B.; Irwin, J.S.

    1987-01-01

    The results from tracer experiments carried out at the Teruel power plant in Spain are presented. Tracer data have been used to present concentration distributions, SO{sub 2} rates and to indicate future measurement locations. The position, extent and area of high SO{sub 2} concentrations are presented. A follow-up program is also indicated. 13 refs., 20 figs., 8 tabs.

  15. Probability Distribution Function of a Forced Passive Tracer in the Lower Stratosphere

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The probability distribution function (PDF) of a passive tracer, forced by a "mean gradient", is studied. First, we take two theoretical approaches, the Lagrangian and the conditional closure formalisms, to study the PDFs of such an externally forced passive tracer. Then, we carry out numerical simulations for an idealized random flow on a sphere and for European Center for Medium-Range Weather Forecasts (ECMWF) stratospheric winds to test whether the mean-gradient model can be applied to studying stratospheric tracer mixing in midlatitude surf zones, in which a weak and poleward zonal-mean gradient is maintained by tracer leakage through polar and tropical mixing barriers, and whether the PDFs of tracer fluctuations in midlatitudes are consistent with the theoretical predictions. The numerical simulations show that when diffusive dissipation is balanced by the mean-gradient forcing, the PDF in the random flow and the Southern-Hemisphere PDFs in ECMWF winds show time-invariant exponential tails, consistent with theoretical predictions. In the Northern Hemisphere, the PDFs exhibit non-Gaussian tails. However, the PDF tails are not consistent with theoretical expectations. The long-term behavior of the PDF tails of the forced tracer is compared to that of a decaying tracer. It is found that the PDF tails of the decaying tracer are time-dependent, and evolve toward flatter than exponential.

  16. Stability of isooctane mixtures with 3-pentanone or biacetyl as fluorescence tracers in combustion experiments

    Science.gov (United States)

    Zhang, Rui; Bohac, Stanislav V.; Sick, Volker

    2006-01-01

    Evidence is presented in the literature that common fluorescence tracer/fuel mixtures used in engine experiments, 3-pentanone/isooctane and biacetyl/isooctane, may decompose during extended use and storage. Investigations presented here show that preferential evaporation of the tracer and not chemical decomposition is responsible for observed decreases in fluorescence signal strength in these experiments.

  17. Slew-rate dependence of tracer magnetization response in magnetic particle imaging.

    Science.gov (United States)

    Shah, Saqlain A; Ferguson, R M; Krishnan, K M

    2014-10-28

    Magnetic Particle Imaging (MPI) is a new biomedical imaging technique that produces real-time, high-resolution tomographic images of superparamagnetic iron oxide nanoparticle tracers. Currently, 25 kHz and 20 mT/μ0 excitation fields are common in MPI, but lower field amplitudes may be necessary for patient safety in future designs. Here, we address fundamental questions about MPI tracer