WorldWideScience

Sample records for cancer tracer synthesis

  1. Prostate Cancer Imaging with Novel PET Tracers.

    Science.gov (United States)

    Lindenberg, Liza; Choyke, Peter; Dahut, William

    2016-03-01

    Molecular imaging of prostate cancer is in a dynamic phase of development. Currently approved techniques are limited and researchers have been working on novel agents to improve accuracy in targeting and detecting prostate tumors. In addition, the complexity of various prostate cancer states also contributes to the challenges in evaluating suitable radiotracer candidates. We have highlighted nuclear medicine tracers that focus on mechanisms involved in bone metastasis, prostate cancer cell membrane synthesis, amino acid analogs, androgen analogs, and the prostate specific membrane antigen. Encouraging results with many of these innovative radiotracer compounds will not only advance diagnostic capabilities for prostate cancer but open opportunities for theranostic applications to treat this worldwide malignancy. PMID:26874530

  2. Synthesis and preliminary biological evaluation of S-11C-methyl-D-cysteine as a new amino acid PET tracer for cancer imaging.

    Science.gov (United States)

    Huang, Tingting; Tang, Ganghua; Wang, Hongliang; Nie, Dahong; Tang, Xiaolan; Liang, Xiang; Hu, Kongzhen; Yi, Chang; Yao, Baoguo; Tang, Caihua

    2015-04-01

    S-(11)C-methyl-L-cysteine (LMCYS) is an attractive amino acid tracer for clinical tumor positron emission tomography (PET) imaging. D-isomers of some radiolabeled amino acids are potential PET tracers for tumor imaging. In this work, S-(11)C-methyl-D-cysteine (DMCYS), a D-amino acid isomer of S-(11)C-methyl-cysteine for tumor imaging was developed and evaluated. DMCYS was prepared by (11)C-methylation of the precursor D-cysteine, with an uncorrected radiochemical yield over 50 % from (11)CH3I within a total synthesis time from (11)CO2 about 12 min. In vitro competitive inhibition studies showed that DMCYS uptake was primarily transported through the Na(+)-independent system L, and also the Na(+)-dependent system B(0,+) and system ASC, with almost no system A. In vitro incorporation experiments indicated that almost no protein incorporation was found in Hepa 1-6 hepatoma cell lines. Biodistribution studies demonstrated higher uptake of DMCYS in pancreas and liver at 5 min post-injection, relatively lower uptake in brain and muscle, and faster radioactivity clearance from most tissues than those of L-isomer during the entire observation time. In the PET imaging of S180 fibrosarcoma-bearing mice and turpentine-induced inflammatory model mice, 2-(18)F-fluoro-2-deoxy-D-glucose (FDG) exhibited significantly high accumulation in both tumor and inflammatory lesion with low tumor-to-inflammation ratio of 1.40, and LMCYS showed low tumor-to-inflammation ratio of 1.64 at 60 min post-injection. By contrast, DMCYS showed moderate accumulation in tumor and very low uptake in inflammatory lesion, leading to relatively higher tumor-to-inflammation ratio of 2.25 than (11)C-methyl-L-methionine (MET) (1.85) at 60 min post-injection. Also, PET images of orthotopic transplanted glioma models demonstrated that low uptake of DMCYS in normal brain tissue and high uptake in brain glioma tissue were observed. The results suggest that DMCYS is a little better than the corresponding L

  3. 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

  4. Alternative PET tracers in head and neck cancer. A review

    NARCIS (Netherlands)

    Wedman, Jan; Pruim, Jan; Roodenburg, Jan L. N.; Halmos, Gyorgy; Langedijk, Johannes A.; Dierckx, Rudi A. J. O.; van der Laan, Bernard F. A. M.

    2013-01-01

    Positron emission tomography (PET) has become a standard in staging Head and Neck cancer. While F-18-fluoro-2-deoxy-d-glucose (FDG) is the most frequently used radiopharmaceutical, glycolysis is not the only metabolic process that can be visualized. Different PET tracers can also be used to visualiz

  5. The role of new PET tracers for lung cancer.

    Science.gov (United States)

    Szyszko, Teresa A; Yip, Connie; Szlosarek, Peter; Goh, Vicky; Cook, Gary J R

    2016-04-01

    18F-fluorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography (PET/CT) is established for characterising indeterminate pulmonary nodules and staging lung cancer where there is curative intent. Whilst a sensitive technique, specificity for characterising lung cancer is limited. There is recognition that evaluation of other aspects of abnormal cancer biology in addition to glucose metabolism may be more helpful in characterising tumours and predicting response to novel targeted cancer therapeutics. Therefore, efforts have been made to develop and evaluate new radiopharmaceuticals in order to improve the sensitivity and specificity of PET imaging in lung cancer with regards to characterisation, treatment stratification and therapeutic monitoring. 18F-fluorothymidine (18F-FLT) is a marker of cellular proliferation. It shows a lower accumulation in tumours than 18F-FDG as it only accumulates in the cells that are in the S phase of growth and demonstrates a low sensitivity for nodal staging. Its main role is in evaluating treatment response. Methionine is an essential amino acid. 11C-methionine is more specific and sensitive than 18F-FDG in differentiating benign and malignant thoracic nodules. 18Ffluoromisonidazole (18F-FMISO) is used for imaging tumour hypoxia. Tumour response to treatment is significantly related to the level of tumour oxygenation. Angiogenesis is the process by which new blood vessels are formed in tumours and is involved in tumour growth and metastatic tumour spread and is a therapeutic target. Most clinical studies have focused on targeted integrin PET imaging of which αvβ3 integrin is the most extensively investigated. It is upregulated on activated endothelial cells in association with tumour angiogenesis. Neuroendocrine tumour tracers, particularly 68Ga-DOTA-peptides, have an established role in imaging of carcinoid tumours. Whilst most of these tracers have predominantly been used in the research environment, they offer

  6. 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.)

  7. Optimization of microfluidic PET tracer synthesis with Cerenkov imaging.

    Science.gov (United States)

    Dooraghi, Alex A; Keng, Pei Y; Chen, Supin; Javed, Muhammad R; Kim, Chang-Jin C J; Chatziioannou, Arion F; van Dam, R Michael

    2013-10-01

    Microfluidic technologies provide an attractive platform for the synthesis of radiolabeled compounds. Visualization of radioisotopes on chip is critical for synthesis optimization and technological development. With Cerenkov imaging, beta particle emitting isotopes can be localized with a sensitive CCD camera. In order for Cerenkov imaging to also serve as a quantitative tool, it is necessary to understand how material properties relevant to Cerenkov emission, namely, index of refraction and beta particle stopping power, affect Cerenkov light output. In this report, we investigate the fundamental physical characteristics of Cerenkov photon yield at different stages of [(18)F]FDG synthesis on the electrowetting on dielectric (EWOD) microfluidic platform. We also demonstrate how Cerenkov imaging has enabled synthesis optimization. Geant4, a Monte Carlo program applied extensively in high energy physics, is used to simulate Cerenkov photon yield from (18)F beta particles traversing materials of interest during [(18)F]FDG synthesis on chip. Our simulations show that the majority (approximately two-thirds) of the (18)F beta particle energy available to produce Cerenkov photons is deposited on the glass plates of the EWOD chip. This result suggests the possibility of using a single calibration factor to convert Cerenkov signal to radioactivity, independent of droplet composition. We validate our simulations with a controlled measurement examining varying ratios of [(18)O]H2O, dimethyl sulfoxide (DMSO), and acetonitrile (MeCN), and find a consistent calibration independent of solvent composition. However, the calibration factor may underestimate the radioactivity in actual synthesis due to discoloration of the droplet during certain steps of probe synthesis. In addition to the attractive quantitative potential of Cerenkov imaging, this imaging strategy provides indispensable qualitative data to guide synthesis optimization. We are able to use this imaging technique to

  8. 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 art...

  9. 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.

  10. 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.

  11. 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.

  12. Tracer kinetic model selection for dynamic contrast-enhanced magnetic resonance imaging of locally advanced cervical cancer

    DEFF Research Database (Denmark)

    Kallehauge, Jesper Folsted; Tanderup, Kari; Duan, Chong;

    2014-01-01

    conditions the Tofts (TM), extended Tofts (ETM), compartmental tissue uptake model (C-TU) and 2-compartment exchange model (2CXM) were the optimal tracer kinetic models (TKMs) for the analysis of DCE-MRI in patients with cervical cancer. Material and methods. Ten patients with locally advanced cervical...

  13. 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)

  14. 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.

  15. A validation of the application of D2O stable isotope tracer techniques for monitoring day-to-day changes in muscle protein subfraction synthesis in humans

    OpenAIRE

    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

    2013-01-01

    Quantification of muscle protein synthesis (MPS) remains a cornerstone for understanding the control of muscle mass. Traditional [13C]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 a...

  16. 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

    the flood prime appeared immediately in the muscle free pool of amino acids and that this abundance could be kept constant by a subsequent continuous infusion of the tracer. When using phenylalanine as tracer, the flood-primed, continuous infusion protocol does not stimulate the MPS rate per se....... In conclusion, the flood-primed, continuous infusion protocol using phenylalanine as tracer can validly be used to measure the protein synthesis rate in human in vivo experiments by obtaining only a single tissue biopsy after a prolonged infusion period....

  17. 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.)

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

    International Nuclear Information System (INIS)

    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 (-1). Without a tracer, detection of newly accumulated Zn is significant at Zn exposure concentration only above 5000 μg 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. - ZnO nanoparticles with distinct isotopic composition can be tailor synthesized to be used as tracers of environmental fate and uptake by organisms.

  19. Synthesis, characterization, biodistribution and scintigraphy of 99mTc-paclitaxel. A potential tracer of paclitaxel

    International Nuclear Information System (INIS)

    99mTc-paclitaxel was synthesized by using sodium borohydride as a reducing agent. Greater than 95 % labelling efficiency was achieved. Radiochemical purity of the synthesized 99mTc-paclitaxel was validated by thin layer chromatography (TLC) scanner and high performance liquid chromatography (HPLC). 99mTc-paclitaxel passed in vitro stability tests. Biodistribution and scintigraphy studies were performed in Sprague-Dawley rats. The biodistribution study results of 99mTc-paclitaxel were related mainly to the metabolism and excretion routes followed by the parental drug, paclitaxel. Apart from that, biodistribution of 99mTc-paclitaxel was altered after pre-treatment with cold paclitaxel. Hence, 99mTc-paclitaxel may be used as a tracer for paclitaxel. (author)

  20. 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

  1. Feasibility of Real-Time Near-Infrared Fluorescence Tracer Imaging in Sentinel Node Biopsy for Oral Cavity Cancer Patients

    DEFF Research Database (Denmark)

    Christensen, Anders; Juhl, Karina; Charabi, Birgitte;

    2016-01-01

    be identified in vivo using NIRF imaging, and the majority of those were located in level 1 close to the primary tumor. CONCLUSIONS: A combined fluorescent and radioactive tracer for SNB is feasible, and the additional use of NIRF imaging may improve the accuracy of SN identification in oral cancer patients......BACKGROUND: Sentinel node biopsy (SNB) is an established method in oral squamous cell carcinoma (OSCC) for staging the cN0 neck and to select patients who will benefit from a neck dissection. Near-infrared fluorescence (NIRF) imaging has the potential to improve the SNB procedure by facilitating...

  2. Guiding principles for estimation of whole-body synthesis rates by tracer experiments

    International Nuclear Information System (INIS)

    Methodical recommendations are suggested-predominantly for laboratory and small animals (rats and young chickens)-for the determination of parameters of the protein metabolism of the whole body after single dosis of a mixture of 15N-labelled amino acids by means of the determination of the temporal course of cumulative 15N excretion in urine and the assessment of the tracer kinetic data in a compartment model. These recommendations are to make it possible to carry out purposefully such experiments under comparable conditions. The advantages of this method are: (1) the non-invasive character of the method; (2) the possibility of repeating the experiment with the same animal; (3) the adaptability to other methods of investigation (e.g. measuring energy metabolism); (4) the relatively low expenditure of labour and requirement of test animals; (5) the relatively good reproducibility of the method. Thus this method is a good supplement to the flooding and permanent infusion methods and should be used wherever the determination of parameters of the protein metabolism of the total body is sufficient. (author)

  3. 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

  4. A comparative study of methylene blue dye and methylene blue with radioactive tracer in breast cancer sentinel node mapping

    International Nuclear Information System (INIS)

    Sentinel lymph node (SLN) biopsy was performed in 72 women with primary breast cancer. During the SLN biopsy, blue dye was used in 18 patients (blue dye; B group), and methylene blue associated with radioactive tracer was used with rhenium colloid in 12 patients (R group) and with phytate in 42 patients (F group). The identification rate of SLNs was 83.3% in the B group, 91.7% in the R group, and 92.9% in the F group. The frequency of SLNs was higher in the B group than in the R or the F group. Back up lymph node dissection was performed in all cases following the identification of SLNs. The rate of accurate identification was 93.3% in the B group, 90.9% in the R group, and 92.3% in the F group. In conclusion, the identification rate was lower in the B group than in the R or the F group, suggesting that methylene blue associated with radioactive tracer using rhenium colloid or phytate may improve the reliability of SLN biopsy. (author)

  5. Automated synthesis of novel cell death imaging tracer 18F-FPDuramycin

    International Nuclear Information System (INIS)

    Background: The noninvasive imaging of cell death plays an important role in the evaluation of degenerative diseases and detection of tumor treatments. Duramycin, a peptide with 19-amino acid, is produced by Streptoverticillium cinnamoneus. It binds specifically to phosphatidylethanolamine (PE), a novel molecular target for cell death. Purpose: The aim is to develop a synthetic method to label duramycin using 18F ion. The automated synthesis was carried out by multi-step procedure on the modified PET-MF-2V-IT-I synthesizer. Methods: Firstly, the prosthetic group of 4-nitrophenyl 2-[18F]fluoropropionate (18F-NFP) was automatically synthesized by a convenient three-step procedure. Secondly, 18F-FPDuramycin was synthesized by conjunction of 18F-NFP with duramycin, which was purified by a solid-phase extraction cartridge. Orthogonal test was performed to confirm the suitable reaction conditions (solvent, base and temperature). Results: The radiochemical yields of 18F-NFP were (25±5)% (n=10, decay-uncorrected) based on[18F]fluoride in 80 min. 18F-FPDuramycin was obtained with yield of (70±3)% (n=8, decay-uncorrected) based on 18F-NFP within 20 min. The radiochemical purity of 18F-FPDuramycin was greater than 99% and the specific activity was greater than (23.7±13.7) GBq·μmol-1 (n=10). Conclusion: 18F-FPDuramycin injection is easy to be prepared with 'two-pot reaction' and is a promising radiotracer used for the clinical and scientific study on positron emission tomography (PET) imaging. (authors)

  6. 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...

  7. [18F]Fluoroazabenzoxazoles as potential amyloid plaque PET tracers: synthesis and in vivo evaluation in rhesus monkey

    International Nuclear Information System (INIS)

    Introduction: An 18F-labeled positron emission tomography (PET) tracer for amyloid plaque is desirable for early diagnosis of Alzheimer's disease, particularly to enable preventative treatment once effective therapeutics are available. Similarly, such a tracer would be useful as a biomarker for enrollment of patients in clinical trials for evaluation of antiamyloid therapeutics. Furthermore, changes in the level of plaque burden as quantified by an amyloid plaque PET tracer may provide valuable insights into the effectiveness of amyloid-targeted therapeutics. This work describes our approach to evaluate and select a candidate PET tracer for in vivo quantification of human amyloid plaque. Methods: Ligands were evaluated for their in vitro binding to human amyloid plaques, lipophilicity and predicted blood–brain barrier permeability. Candidates with favorable in vitro properties were radiolabeled with 18F and evaluated in vivo. Baseline PET scans in rhesus monkey were conducted to evaluate the regional distribution and kinetics of each tracer using tracer kinetic modeling methods. High binding potential in cerebral white matter and cortical grey matter was considered an unfavorable feature of the candidate tracers. Results: [18F]MK-3328 showed the most favorable combination of low in vivo binding potential in white matter and cortical grey matter in rhesus monkeys, low lipophilicity (Log D=2.91) and high affinity for human amyloid plaques (IC50=10.5±1.3 nM). Conclusions: [18F]MK-3328 was identified as a promising PET tracer for in vivo quantification of amyloid plaques, and further evaluation in humans is warranted.

  8. Effects of 2-methoxyestradiol on proliferation, apoptosis and PET-tracer uptake in human prostate cancer cell aggregates

    Energy Technology Data Exchange (ETDEWEB)

    Davoodpour, Padideh; Bergstroem, Mats; Landstroem, Marene E-mail: Marene.Landstrom@LICR.uu.se

    2004-10-01

    The purpose of this study was to investigate the potential use of PET in vivo to record cytotoxic effects of 2-methoxyestradiol (2-ME), an endogenous metabolite of 17{beta}-estradiol. The anti-proliferative and pro-apoptotic effects of 2-ME on human prostate cancer cell (PC3) aggregates in vitro, were correlated with the uptake of fluoro-deoxy-D-glucose, FMAU and choline labelled with {sup 18}F, {sup 11}C, or {sup 3}H. 2-ME clearly reduced growth of PC3 aggregates and induced apoptosis in a dose-dependent manner. However, the uptake of the putative proliferation markers {sup 11}C-FMAU or {sup 3}H-choline failed to record the growth inhibitory effects of 2-ME on PC3 cell aggregates. The uptake of {sup 18}F-FDG was used as a marker for effects on cellular metabolism and also failed to show any dose-dependent effects in PC3 aggregates. The use of these PET-tracers in vivo is therefore not recommended in order to evaluate the cytotoxic effects of 2-ME on human prostate cancer cells.

  9. 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.

  10. Validation of a single biopsy approach and bolus protein feeding to determine myofibrillar protein synthesis in stable isotope tracer studies in humans

    Directory of Open Access Journals (Sweden)

    Baker Steven K

    2011-03-01

    Full Text Available Abstract Background Minimizing the number of muscle biopsies has important methodological implications and minimizes subject discomfort during a stable isotope amino acid infusion. We aimed to determine the reliability of obtaining a single muscle biopsy for the calculation of muscle protein fractional synthetic rate (FSR as well as the amount of incorporation time necessary to obtain that biopsy after initiating a stable isotope infusion (Study 1. The calculation of muscle protein FSR requires tracer steady-state during the stable isotope infusion. Therefore, a second aim was to examine if steady-state conditions are compromised in the precursor pools (plasma free or muscle intracellular [IC] after ingestion of a tracer enriched protein drink and after resistance exercise (Study 2. Methods Sixteen men (23 ± 3 years; BMI = 23.8 ± 2.2 kg/m2, means ± SD were randomized to perform Study 1 or Study 2 (n = 8, per study. Subjects received a primed, constant infusion of L-[ring-13C6]phenylalanine coupled with muscle biopsies of the vastus lateralis to measure rates of myofibrillar protein synthesis (MPS. Subjects in Study 2 were fed 25 g of whey protein immediately after an acute bout of unilateral resistance exercise. Results There was no difference (P = 0.3 in rates of MPS determined using the steady-state precursor-product equation and determination of tracer incorporation between sequential biopsies 150 min apart or using plasma protein as the baseline enrichment, provided the infusion length was sufficient (230 ± 0.3 min. We also found that adding a modest amount of tracer (4% enriched, calculated based on the measured phenylalanine content of the protein (3.5% in the drink, did not compromise steady-state conditions (slope of the enrichment curve not different from zero in the plasma free or, more importantly, the IC pool (both P > 0.05. Conclusions These data demonstrate that the single biopsy approach yields comparable rates of muscle

  11. 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.)

  12. 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.

  13. 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.

  14. Improved synthesis of 17β-hydroxy-16α-iodo-wortmannin, 17β-hydroxy-16α-iodoPX866, and the [131I] analogue as useful PET tracers for PI3-kinase

    OpenAIRE

    Sun, Duoli; Basvoju A. Bhanu Prasad; Schuber, Paul T.; Peng, Zhenghong; Maxwell, David S.; Martin, Diana V.; Guo, Liwei; Han, Dongmei; Kurihara, Hiroaki; Yang, David J.; Gelovani, Juri G.; Powis, Garth; Bornmann, William G.

    2013-01-01

    An improved method for the synthesis of 17β-hydroxy-16α-iodo-wortmannin along with the first synthesis of 17β-hydroxy-16α-iodoPX866 and [131I] radiolabeled 17β-hydroxy-16α-[131I]iodo-wortmannin, as potential PET tracers for PI3K was also described. The differences between wortmannin and its iodo analogue were compared by covalently docking each structure to L833 in PI3K.

  15. Development of a new structure for in vivo tracers synthesis: application to tumor neo-angiogenesis imaging

    International Nuclear Information System (INIS)

    Molecular imaging is an essential non-invasive tool usable for diagnosis and characterisation of many diseases. Technetium-based tracers are the most popular ones due to availability, cost and radiochemical properties of 99mTc. Nevertheless, effective tracers development requires a long, expensive, and mainly empirical optimisation process. This context prompted us to carry on the development of a new technetium structure which exhibits lots of potential functionalization spots compatible with a combinatorial approach. We synthesised 12 N3X (X = N, O, S) different ligands. Each of them includes a triazole moiety, (formed via a click-chemistry reaction), which is involved in the metal complexation that implies one of its nitrogen atoms. Then we evaluated their ability to readily form oxo-technetium complexes in conditions that are compatible with medical use in hospital. One complex was formed in quantitative yields and its stability in mice plasma was investigated. A complex called TriaS-99mTc, stable to more than 90% after 6 h incubation, was selected. In vivo study of TriaS-99mTc revealed an efficient blood clearance via the urinary excretion pathway with very low degradation. As an application, we used this structure for the development of tracers that target integrin αvβ3, a known bio-marker of tumor neo-angiogenesis. First, we synthesised functionalized TriaS-based integrated complexes. Functional modification of TriaS by addition of side chains and substituents did not affect its ability to chelate oxo-technetium quantitatively. In addition, its stability in mice plasma was satisfactory. We also developed a bifunctional approach using c(RGDfK) peptide as the targeting biomolecule. In this way, a variable moiety (herein a PEG moiety) can be inserted in the structure through click-chemistry in order to modulate tracers solubility, biodistribution and excretion. (author)

  16. 6-[18F]fluoro-L-fucose: A possible tracer for assessing glycoconjugate synthesis in tumors with positron emission tomography

    International Nuclear Information System (INIS)

    The potential of 6-[18F]fluoro-L-fucose (6-[18F]FFuc) for assessing glycoconjugate synthesis in tumors with positron emission tomography (PET) was investigated. Using the tissue sampling method with five tumor models, different time-radioactivity profiles were found: a nearly constant level in Lewis lung carcinoma (3LL) and different clearance patterns in others. Rapid clearance in normal tissues resulted in preferable uptake ratios for tumor imaging of brain and pancreas. Metabolic studies and the L-fucose loading effects on the tissue uptake proved the tracer to be a biochemically active L-fucose analog. Imaging of the intracranial rat glioma and 3LL in lungs or hepatomas in mice by autoradiography (ARG) and intramuscular VX-2 carcinoma in rabbits by PET was demonstrated. Using double-radionuclide ARG, similar distribution images of 6-[18F]FFuc and 14C-L-fucose but different tumor-to-liver uptake ratios were found. A metastasis model seemed to show a higher uptake of both tracers as compared to a primary tumor model

  17. 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

  18. Synthesis and biological evaluation of carbon-11 and fluorine-18 labeled tracers for in vivo visualization of PDE10A

    International Nuclear Information System (INIS)

    Introduction: In vivo visualization of PDE10A using PET provides a tool to evaluate the role of PDE10A in various neuropsychiatric diseases and can also be useful in the clinical evaluation of PDE10A inhibitor drug candidates. We evaluated several carbon-11 and fluorine-18 labeled PDE10A inhibitors as potential PDE10A PET radioligands. Materials and Methods: [11C]MP10, [11C]JNJ42071965 and four other tracers were developed. Their biodistribution was evaluated in rats. Rat plasma and brain radiometabolites were quantified. Baseline microPET imaging was performed in normal rats and PDE10A knockout (KO) and wild-type (WT) mice. Blocking and displacement studies were conducted. The selectivity of the tracer binding was further studied in an ex vivo autoradiography experiment in PDE10A KO and WT mice. Results: Biodistribution showed brain uptake for all tracers in the striatum and wash-out from the cerebellum. [11C]1 (11C-MP10) had the highest specific uptake index (striatum (S) vs. cerebellum (C) ratios (S/C)-1) at 60 min (7.4). [11C]5 ([11C]JNJ42071965) had a high index at the early time points (1.0 and 3.7 at 2 and 30 min p.i., respectively). The affinity of [11C]4, [18 F]3 and [18 F]6 was too low to visualize PDE10A using microPET. [11C] 2 showed a specific binding, while kinetics of [11C]1 were too slow. [11C]5 reached equilibrium after 10 min (uptake index = 1.2). Blocking and displacement experiments in rats and baseline imaging in PDE10A KO mice showed specific and reversible binding of [11C]5 to PDE10A. Conclusions: We successfully radiolabeled and evaluated six radiotracers for their potential to visualize PDE10A in vivo. While [11C]1 had the highest striatal specific uptake index, its slow kinetics likely compromise clinical use of this tracer. [11C]5 has a relatively high striatum-to-background ratio and fast kinetic profile, which makes it a valuable carbon-11 alternative

  19. Synthesis of New Anti-Cancer Natural Products

    DEFF Research Database (Denmark)

    Yu, Wanwan

    2016-01-01

    the synthetic entry into this structurally and biologically interesting class of natural products challenging. To date, there is only the one synthesis publication of the STR family that is developed by our lab, which present research also discussed within this dissertation. The synthetic development......) lactonization. The entire STR project was divided into two stages: stage-1, the semisynthesis of STR-2, -3, -8; stage-2, a method development and application in the synthesis of STR-26. The efficient synthetic entry finally delivered the syntheses of eight STR members included the most cancer disease related...

  20. 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

    2016-08-01

    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. PMID:27123902

  1. A novel PET tracer for the imaging of αvβ3 and αvβ5 integrins in experimental breast cancer bone metastases.

    Science.gov (United States)

    Mühlhausen, Ute; Komljenovic, Dorde; Bretschi, Maren; Leotta, Karin; Eisenhut, Michael; Semmler, Wolfhard; Bäuerle, Tobias

    2011-01-01

    The aim of this study was the evaluation of (68)Ga-DOTA-E-[c(RGDfK)](2) as a novel PET tracer to image αvβ3 and αvβ5 integrins. For this purpose, DOTA-E-[c(RGDfK)](2) was labeled with (68)Ga, which was obtained from a (68)Ge/(68)Ga generator, purified by solid-phase extraction and the radiochemical purity analyzed by radio-RP-HPLC. (68) Ga-DOTA-E-[c(RGDfK)](2) was obtained reproducibly in radiochemical yields of 60 ± 6% and with an excellent radiochemical purity of >99%. In nude rats bearing bone metastases after injection of MDA-MB-231 human breast cancer cells, biodistribution studies were performed to evaluate the accumulation of the radiotracer in selected organs, blood and bone metastases 0.5, 1, 2 and 3 h post injection. A rapid uptake into the bone metastases and rapid blood clearance was observed, resulting in tumor-blood ratios of up to 26.6 (3 h post injection) and tumor-muscle ratios of up to 7.9 (3 h post injection). A blocking experiment with coinjected αvβ3/αvβ5 antagonist showed the tumor uptake to be receptor-specific. In an initial in vivo micro PET evaluation of the tracer using the same animal model, the bone metastasis was clearly visualized. These results suggest that (68)Ga-DOTA-E-[c(RGDfK)](2) is a promising PET tracer suitable for the imaging of αvβ3 and αvβ5 integrins in bone metastases. This novel PET tracer should be further evaluated concerning its usefulness for early detection of bone metastases and monitoring treatment response of these lesions. PMID:22162137

  2. A Practical One-Pot Synthesis of Positron Emission Tomography (PET) Tracers via Nickel-Mediated Radiofluorination.

    Science.gov (United States)

    Zlatopolskiy, Boris D; Zischler, Johannes; Urusova, Elizaveta A; Endepols, Heike; Kordys, Elena; Frauendorf, Holm; Mottaghy, Felix M; Neumaier, Bernd

    2015-08-01

    Invited for this months cover picture is the group of Professor Bernd Neumaier at the Institute of Radiochemistry and Experimental Molecular Imaging at the University Clinic of Cologne. The cover picture shows the differences in brain metabolism of a healthy young and a healthy old subject, as well as a patient suffering from Parkinsons disease (left to right) uncovered by 6-[(18)F]FDOPA-positron emission tomography (PET). Morbus Parkinson occurs when nerve cells that produce dopamine begin to die. The shortage of dopamine leads to movement problems in affected individuals. 6-[(18)F]FDOPA is extensively used to evaluate the progression of Parkinsons disease. Bold stick projections of this PET tracer, as well as a neuronal network, are seen in the background. Unfortunately, conventional procedures to produce 6-[(18)F]FDOPA are cumbersome. Thus, several recent developments aim at the simplification of this radiosynthesis. In our work, we studied the applicability of the recently reported Ni-mediated radiofluorination approach for daily routine production of 6-[(18)F]FDOPA. For more details, see the Full Paper on p. 457 ff. PMID:26478831

  3. 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.

  4. 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.

  5. Predicting gemcitabine transport and toxicity in human pancreatic cancer cell lines with the positron emission tomography tracer 3'-deoxy-3'-fluorothymidine.

    Science.gov (United States)

    Paproski, Robert J; Young, James D; Cass, Carol E

    2010-02-15

    The abundance of human equilibrative nucleoside transporter 1 (hENT1) has recently been shown to be a predictive marker of benefit from gemcitabine therapy in patients with pancreatic cancer. Since hENT1 is also important for the uptake of positron emission tomography (PET) tracer 3'-deoxy-3'-fluorothymidine (FLT) in various cultured human cell lines, this study was undertaken to determine if FLT uptake predicts gemcitabine uptake and/or toxicity in a panel of human pancreatic cancer cell lines (Capan-2, AsPC-1, BxPC-3, PL45, MIA PaCa-2, and PANC-1). Capan-2 cells displayed the lowest levels of (1) extracellular nitrobenzylmercaptopurine ribonucleoside (NBMPR) binding, which represents cell-surface hENT1, (2) FLT and gemcitabine uptake during short (1-45s) and prolonged (1h) periods, and (3) gemcitabine sensitivity. Exposure to NBMPR (inhibits only hENT1) or dilazep (inhibits hENT1 and hENT2) reduced FLT and gemcitabine uptake and gemcitabine sensitivity, with dilazep having greater effects than NBMPR. Gemcitabine permeation was almost completely mediated, primarily by hENT1 and to a lesser extent by hENT2, whereas FLT permeation included a substantial component of passive diffusion. In five of six cell lines, correlations were observed between (1) FLT and gemcitabine initial rates of uptake, (2) gemcitabine uptake and gemcitabine toxicity, (3) FLT uptake and gemcitabine toxicity, and (4) ribonucleotide reductase subunit M1 expression and gemcitabine toxicity. FLT and gemcitabine uptake were comparable for predicting gemcitabine toxicity in the tested pancreatic cancer cell lines suggesting that FLT PET may provide clinically useful information about tumor gemcitabine transport capacity and sensitivity. PMID:19788890

  6. Reduced arginine availability and nitric oxide synthesis in cancer is related to impaired endogenous arginine synthesis.

    Science.gov (United States)

    Engelen, Mariëlle P K J; Safar, Ahmed M; Bartter, Thaddeus; Koeman, Fari; Deutz, Nicolaas E P

    2016-07-01

    Reduced plasma arginine (ARG) concentrations are found in various types of cancer. ARG and its product nitric oxide (NO) are important mediators in the immune function and the defense against tumour cells. It remains unclear whether the diminished systemic ARG availability in cancer is related to insufficient endogenous ARG synthesis, negatively affecting NO synthesis, and whether a dietary amino acid mixture is able to restore this. In 13 patients with advanced non-small cell lung cancer (NSCLC) and 11 healthy controls, whole body ARG and CIT (citrulline) rates of appearance were measured by stable isotope methodology before and after intake of a mixture of amino acids as present in whey protein. The conversions of CIT to ARG (indicator of de novo ARG synthesis) and ARG to CIT (marker of NO synthesis), and ARG clearance (reflecting ARG disposal capacity) were calculated. Plasma isotopic enrichments and amino acid concentrations were measured by LC-MS/MS. Conversions of CIT to ARG and ARG to CIT (P<0.05), and CIT rate of appearance (P=0.07) were lower in NSCLC. ARG rate of appearance and clearance were comparable suggesting no enhanced systemic ARG production and disposal capacity in NSCLC. After intake of the mixture, ARG rate of appearance and concentration increased (P<0.001), and ARG to CIT conversion was restored in NSCLC. In conclusion, an impaired endogenous ARG synthesis plays a role in the reduced systemic ARG availability and NO synthesis in advanced NSCLC. Nutritional approaches may restore systemic ARG availability and NO synthesis in cancer, but the clinical implication remains unclear. PMID:27129191

  7. Dual-tracer receptor concentration imaging using tracers with different tissue delivery kinetics

    Science.gov (United States)

    Tichauer, Kenneth M.; Diop, Mamadou; Elliott, Jonathan T.; Samkoe, Kimberley S.; Hasan, Tayyaba; St. Lawrence, Keith; Pogue, Brian W.

    2014-03-01

    Simultaneous dynamic fluorescent imaging of a suitable untargeted tracer in conjunction with any molecular targeted fluorescent agent has been shown to be a powerful approach for quantifying cancer-specific cell surface receptors in vivo in the presence of non-specific uptake and tracer delivery variability. The identification of a "suitable" untargeted tracer (i.e., one having equivalent plasma and tissue delivery pharmacokinetics to the targeted tracer) for every targeted tracer, however, may not always be feasible or could require extensive testing. This work presents a "deconvolution" approach capable of correcting for plasma and tissue-delivery pharmacokinetic differences between tracers by quantifying dynamic differences in targeted and untargeted tracer uptake in a receptor-free tissue (one devoid of targeted molecular species) and correcting uptake in all other tissues accordingly. This deconvolution correction approach is evaluated in theoretical models and explored in an in vivo mouse xenograft model of human glioma. In the animal experiments, epidermal growth factor receptor (EGFR: a receptor known to be overexpressed in the investigated glioma cell line) was targeted using a fluorescent tracer with very different plasma pharmacokinetics than a second untargeted fluorescent tracer. Without correcting for these differences, the dual-tracer approach yielded substantially higher estimations of EGFR concentration in all tissues than expected; however, deconvolution correction was able to produce estimates that matched ex vivo validation.

  8. Exploring Spatial Overlap of High-Uptake Regions Derived From Dual Tracer Positron Emission Tomography–Computer Tomography Imaging Using 18F-Fluorodeoxyglucose and 18F-Fluorodeoxythymidine in Nonsmall Cell Lung Cancer Patients

    OpenAIRE

    Liu, Jing; Li, Chengqiang; Hu, Man; Lu, Jie; Shi, Xiaorong; XING, LIGANG; Sun, Xindong; FU, ZHENG; YU, JINMING; MENG, XUE

    2015-01-01

    Abstract Interest is growing in radiotherapy to nonuniformly boost radioresistant regions within nonsmall cell lung cancer (NSCLC) using molecular imaging techniques. The complexity of tumor behavior is beyond the ability of any single radiotracer to reveal. We hold dual tracer positron emission tomography–computer tomography (PET/CT) imaging with fluorodeoxyglucose (FDG) and fluorodeoxythymidine (FLT) for NSCLC patients to offer an integrated overlook of tumor biological behaviors quantitati...

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. Androgen deprivation promotes intratumoral synthesis of dihydrotestosterone from androgen metabolites in prostate cancer

    OpenAIRE

    Fumio Ishizaki; Tsutomu Nishiyama; Takashi Kawasaki; Yoshimichi Miyashiro; Noboru Hara; Itsuhiro Takizawa; Makoto Naito; Kota Takahashi

    2013-01-01

    Intratumoral synthesis of dihydrotestosterone (DHT) from precursors cannot completely explain the castration resistance of prostate cancer. We showed that DHT was intratumorally synthesized from the inactive androgen metabolites 5α-androstane-3α/β,17β-diol (3α/β-diol) in prostate cancer cells via different pathways in a concentration-dependent manner. Additionally, long-term culture in androgen-deprived media increased transcriptomic expression of 17β-hydroxysteroid dehydrogenase type 6 (HSD1...

  14. Radiopharmaceutical Tracers for Neural Progenitor Cells

    International Nuclear Information System (INIS)

    The Technical Report summarizes the results of the synthesis and microPET animal scanning of several compounds labeled with positron-emitting isotopes in normal, neonatal and kainic acid treated (seizure induced) rats as potential PET tracers to image the process of neurogenesis using positron emission tomography (PET). The tracers tested were 3'-deoxy-3'-[F-18]fluorothymidine ([F-18]FLT) and 5'-benzoyl-FTL, 1-(2'-deoxy-2'-[F-18]fluoro-B-D-arabinofuranosyl)-5-bromouracil (FBAU) and 3',5'-dibenzoyl-FBAU, N-[F-18]fluoroacetyl-D-glucosamine (FLAG) and tetraacetyl-FLAG, and L-[1-C-11]leucine

  15. Design, Synthesis, and In Vitro and In Vivo Evaluation of an (18)F-Labeled Sphingosine 1-Phosphate Receptor 1 (S1P1) PET Tracer.

    Science.gov (United States)

    Rosenberg, Adam J; Liu, Hui; Jin, Hongjun; Yue, Xuyi; Riley, Sean; Brown, Steven J; Tu, Zhude

    2016-07-14

    Sphingosine 1-phosphate receptor 1 (S1P1) plays a pivotal signaling role in inflammatory response; because S1P1 modulation has been identified as a therapeutic target for various diseases, a PET tracer for S1P1 would be a useful tool. Fourteen fluorine-containing analogues of S1P ligands were synthesized and their in vitro binding potency measured; four had high potency and selectivity for S1P1 (S1P1 IC50 100-fold selectivity for S1P1 over S1P2 and S1P3). The most potent ligand, 28c (IC50 = 2.63 nM for S1P1) was (18)F-labeled and evaluated in a mouse model of LPS-induced acute liver injury to determine its S1P1-binding specificity. The results from biodistribution, autoradiography, and microPET imaging showed higher [(18)F]28c accumulation in the liver of LPS-treated mice than controls. Increased expression of S1P1 in the LPS model was confirmed by immunohistochemical analysis (IHC). These data suggest that [(18)F]28c is a S1P1 PET tracer with high potential for imaging S1P1 in vivo. PMID:27280499

  16. 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.

  17. Immediate dynamic lymphoscintigraphy delivers no additional value to lymphoscintigraphy 3 hr after tracer injection in sentinel lymph node biopsy in breast cancer patients

    NARCIS (Netherlands)

    Doting, M. H. Edwina; Stiekema, H. M. Annemiek; de Vries, Jacob; Lemstra, Clara; Hoekstra, Harald J.; Vrieling, Mirjam; Rietman, Lianne; Jager, Pieter L.

    2007-01-01

    Objective: Immediate dynamic imaging enables accurate definition of sentinel lymph nodes, whereas imaging, 3 hr after tracer injection may lead to overestimation of the number of sentinel lymph nodes. A study was performed to define the value of lymphoscintigraphy immediately versus 3 hr after trace

  18. 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.

  19. Suitability of tracers

    International Nuclear Information System (INIS)

    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

  20. Design and synthesis of isosteviol triazole conjugates for cancer therapy.

    Science.gov (United States)

    Khaybullin, Ravil N; Zhang, Mei; Fu, Junjie; Liang, Xiao; Li, Tammy; Katritzky, Alan R; Okunieff, Paul; Qi, Xin

    2014-01-01

    One of the keys for successfully developing drugs against the broad spectrum of cancer cell types is structural diversity. In the current study, we focused on a family of isosteviol derivatives as potential novel antitumor agents. Isosteviol is a tetracyclic diterpenoid obtained by acid hydrolysis of steviol glycoside extracts isolated from abundant Stevia rebaudiana plants. In this work, we have designed and synthesized a panel of isosteviol triazole conjugates using "click" chemistry methodology. Evaluation of these compounds against a series of cancer cell lines derived from primary and metastatic tumors demonstrated that these conjugates exhibit cytotoxic activities with IC50 in the low μM range. In addition, their anti-proliferative activities are cancer cell type specific. Taken together, our studies underscore the importance of structural diversity in achieving cancer cell type specific drug development. PMID:25405286

  1. Design and Synthesis of Isosteviol Triazole Conjugates for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Ravil N. Khaybullin

    2014-11-01

    Full Text Available One of the keys for successfully developing drugs against the broad spectrum of cancer cell types is structural diversity. In the current study, we focused on a family of isosteviol derivatives as potential novel antitumor agents. Isosteviol is a tetracyclic diterpenoid obtained by acid hydrolysis of steviol glycoside extracts isolated from abundant Stevia rebaudiana plants. In this work, we have designed and synthesized a panel of isosteviol triazole conjugates using “click” chemistry methodology. Evaluation of these compounds against a series of cancer cell lines derived from primary and metastatic tumors demonstrated that these conjugates exhibit cytotoxic activities with IC50 in the low μM range. In addition, their anti-proliferative activities are cancer cell type specific. Taken together, our studies underscore the importance of structural diversity in achieving cancer cell type specific drug development.

  2. Quantitative Proteomics: Measuring Protein Synthesis Using 15N Amino Acids Labeling in Pancreas Cancer Cells

    OpenAIRE

    Zhao, Yingchun; Lee, Wai-Nang Paul; Lim, Shu; Go, Vay Liang; Xiao, Jing; Cao, Rui; Zhang, Hengwei; Recker, Robert; Xiao, Gary Guishan

    2009-01-01

    Pancreatic cancer MIA PaCa cells were cultured in the presence and absence of 15N amino acids mixture for 72 hours. During protein synthesis, the incorporation of 15N amino acids results in a new mass isotopomer distribution in protein, which is approximated by the concatenation of two binomial distributions of 13C and 15N. Fraction of protein synthesis (FSR) can thus be determined from the relative intensities of the ‘labeled’ (new) and the ‘unlabeled” (old) spectra. Six prominent spots were...

  3. 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.

  4. 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.

  5. 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.

  6. Synthesis, radiosynthesis, and in vitro evaluation of [131I]-5-iodo-N-[2-(6,7-dimethoxy-3,4-dihydro-1H-isoquinoline-2-yl)-ethyl] -2-methoxy-benzamide as a potential tumor imaging agent

    International Nuclear Information System (INIS)

    This work reports the synthesis, radiolabeling and preliminary in vitro evaluation of [131I]-5-iodo-N-[2-(6,7-dimethoxy-3,4-dihydro-1H-isoquinoline-2-yl)-ethyl] -2-methoxy-benzamide. The tributylstannylprecursor was synthesized with a yield of 38%. Radiolabeling was performed using an electrophilic iododestannylation. Tracer yield was 94%, radiochemical purity was >95%. The tracer showed high uptake in MCF-7 breast cancer cell line and therefore will be evaluated further

  7. Systematic Review and Meta-study Synthesis of Qualitative Studies Evaluating Facilitators and Barriers to Participation in Colorectal Cancer Screening.

    Science.gov (United States)

    Honein-AbouHaidar, Gladys N; Kastner, Monika; Vuong, Vincent; Perrier, Laure; Daly, Corinne; Rabeneck, Linda; Straus, Sharon; Baxter, Nancy N

    2016-06-01

    Screening reduces the incidence, morbidity, and mortality of colorectal cancer, yet participation tends to be low. We undertook a systematic review and meta-study synthesis of qualitative studies to identify facilitators and barriers to colorectal cancer screening participation. We searched major bibliographic databases for records published in all languages from inception to February 2015. Included primary studies that elicited views and perceptions towards colorectal cancer screening were appraised for relevance and quality. We used a two-stage synthesis to create an interpretation of colorectal cancer screening decisions grounded in primary studies; a thematic analysis to group themes and systematically compare studies and a meta-synthesis to generate an expanded theory of colorectal cancer screening participation. Ninety-four studies were included. The decision to participate in colorectal cancer screening depended on an individual's awareness of colorectal cancer screening. Awareness affected views of cancer, attitudes towards colorectal cancer screening modalities, and motivation for screening. Factors mediating awareness included public education to address misconceptions, primary care physician efforts to recommend screening, and the influence of friends and family. Specific barriers to participation in populations with lower participation rates included language barriers, logistical challenges to attending screening tests, and cultural beliefs. This study identifies key barriers, facilitators, and mediators to colorectal cancer screening participation. Cancer Epidemiol Biomarkers Prev; 25(6); 907-17. ©2016 AACR. PMID:27197277

  8. Synthesis, characterization, and functionalization of gold nanoparticles for cancer imaging.

    Science.gov (United States)

    Craig, Gary A; Allen, Peter J; Mason, Michael D

    2010-01-01

    This chapter describes the methodology by which mAb-F19-conjugated gold nanoparticles were prepared and used to label human pancreatic adenocarcinoma. Specifically, gold nanoparticles were coated with dithiol bearing hetero-bifunctional PEG (polyethylene glycol), and cancer-specific mAb F19 was attached by means of NHS-EDC coupling chemistry taking advantage of a carboxylic acid group on the heterobifunctional PEG. These conjugates were completely stable and were characterized by a variety of methods, including UV-Vis absorbance spectrometry, darkfield microscopy, DLS (dynamic light scattering), TEM (transmission electron microscopy), SEC (size-exclusion chromatography), and confocal microscopy. Nanoparticle bioconjugates were used to label sections of healthy and cancerous human pancreatic tissue. Labeled tissue sections were examined by darkfield microscopy and indicate that these nanoparticle bioconjugates may selectively bind to cancerous tissue and provide a means of optical contrast. PMID:20217596

  9. Colonic cancer cell polyamine synthesis after photodynamic therapy

    International Nuclear Information System (INIS)

    PhotoDynamic Therapy is a new concept for cancer treatment based on the interaction between light and a sensitizer, hematoporphyrin derivative (HPD) selectively retained by tumor cells which becomes toxic after light exposure. This effect decreases cell growth, through complex pathways. The aim of this study was to determine whether cellular polyamines, Put (Putrescine), Spd (Spermidine) and Spm (Spermine) were modified after PDT or not. These cations of small molecular weight are essential for cell growth and differentiation of normal and neoplastic cells. In this study intracellular contents of Put, Spd and Spm were determined on 2 sublines of rat colonic cancer cells cloned from the same rat cancer and forming progressive (PROb) and regressive (REGb) tumors. (author). 12 refs., 2 figs

  10. Inhibition of Fatty Acid Synthesis Induces Apoptosis of Human Pancreatic Cancer Cells.

    Science.gov (United States)

    Nishi, Koji; Suzuki, Kenta; Sawamoto, Junpei; Tokizawa, Yuma; Iwase, Yumiko; Yumita, Nagahiko; Ikeda, Toshihiko

    2016-09-01

    Cancer cells tend to have a high requirement for lipids, including fatty acids, cholesterol and triglyceride, because of their rapid proliferative rate compared to normal cells. In this study, we investigated the effects of inhibition of lipid synthesis on the proliferation and viability of human pancreatic cancer cells. Of the inhibitors of lipid synthesis that were tested, 5-(tetradecyloxy)-2-furoic acid (TOFA), which is an inhibitor of acetyl-CoA carboxylase, and the fatty acid synthase (FAS) inhibitors cerulenin and irgasan, significantly suppressed the proliferation of MiaPaCa-2 and AsPC-1 cells. Treatment of MiaPaCa-2 cells with these inhibitors significantly increased the number of apoptotic cells. In addition, TOFA increased caspase-3 activity and induced cleavage of poly (ADP-ribose) polymerase in MiaPaCa-2 cells. Moreover, addition of palmitate to MiaPaCa-2 cells treated with TOFA rescued cells from apoptotic cell death. These results suggest that TOFA induces apoptosis via depletion of fatty acids and that, among the various aspects of lipid metabolism, inhibition of fatty acid synthesis may be a notable target for the treatment of human pancreatic cancer cells. PMID:27630308

  11. Design and Synthesis of Isosteviol Triazole Conjugates for Cancer Therapy

    OpenAIRE

    Ravil N. Khaybullin; Mei Zhang; Junjie Fu; Xiao Liang; Tammy Li; ALAN R. KATRITZKY; Paul Okunieff; Xin Qi

    2014-01-01

    One of the keys for successfully developing drugs against the broad spectrum of cancer cell types is structural diversity. In the current study, we focused on a family of isosteviol derivatives as potential novel antitumor agents. Isosteviol is a tetracyclic diterpenoid obtained by acid hydrolysis of steviol glycoside extracts isolated from abundant Stevia rebaudiana plants. In this work, we have designed and synthesized a panel of isosteviol triazole conjugates using “click” chemistry meth...

  12. Barriers and facilitators to cervical cancer screening in high incidence populations: A synthesis of qualitative evidence.

    Science.gov (United States)

    Driscoll, Susan D

    2016-01-01

    Despite the efficacy and availability of screening and treatment for cervical cancer, it remains the leading cause of death for women in many low resource countries. The inability or reluctance of women to use screening and treatment is the largest contributor to cervical cancer morbidity and mortality. The aim of the author in this article is to determine knowledge, attitudes, and beliefs that facilitate or hinder women's use of screening in high incidence countries through a synthesis of qualitative research. CINAHL, Medline, AnthroSource, Sociological Abstracts, Social Service Abstracts, GenderWatch, Ethnic News Watch, and ASSIA databases were queried for qualitative research published from 2008 to 2013. Ten studies meeting inclusion criteria were reviewed and analyzed using constant comparative analysis. Barriers to cervical cancer screening included fatalism, mistrust of non-traditional healthcare providers, masculine/feminine beliefs, limited knowledge, and misunderstandings of causes of cervical cancer. Facilitators included knowledge of sexual risk factors, recognition of signs and symptoms, and community/social support. Pragmatic solutions suggested by this synthesis, that may decrease barriers and enhance facilitators, involved cultural humility (a continual commitment to cultural competence), promotion of gender equality, collaboration among stakeholders, and the translation of evidence-based practices from low to high incidence populations. PMID:26496628

  13. 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).

  14. 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.

  15. 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.

  16. Hypoxia-induced alteration of tracer accumulation in cultured cancer cells and xenografts in mice: implications for pre-therapeutic prediction of treatment outcomes with 99mTc-sestamibi, 201Tl chloride and 99mTc-HL91

    International Nuclear Information System (INIS)

    Weak visualization of tumours in pre-therapeutic scintigrams with technetium-99m sestamibi (MIBI) is likely a predictive sign of unfavourable tumour response to radiotherapy and chemotherapy. However, factors relating to this scintigraphic finding are not well understood. The presence of hypoxic tumour cells is one of the major reasons for therapeutic failure; consequently, we attempted to determine whether oxygenation status affects 99mTc-MIBI accumulation in tumour cells. LS180 human colon cancer and T24 human bladder cancer cells were incubated in air or N2 gas at 37 C. Cellular uptake of 99mTc-MIBI was subsequently determined at 15, 60 and 120 min. Uptake of thallium-201 chloride was also assessed. Uptake of 99mTc-HL91 was assessed as a hypoxic marker. Accumulation of the tracers in LS180 xenografts was observed in mice treated with 5 mg/kg hydralazine and compared with that in untreated mice. pO2 in the medium and tumours was measured with O2 microelectrodes. N2 gas flow gradually reduced pO2 in the cell suspension to 1-2 mmHg in 60 min. Cellular uptake of 99mTc-MIBI in LS180 cells decreased by approximately 30% in N2 gas in comparison to that in air throughout the study. Hypoxia had a more prominent influence on 201Tl uptake, which displayed a reduction of approximately 60% in N2 gas at 120 min, than on 99mTc-MIBI uptake. On the other hand, N2 gas induced an increase of 170% in 99mTc-HL91 uptake at 120 min, indicating the hypoxic condition of cells. The results of in vitro assays employing the T24 cell line were similar to those obtained with the LS180 cell line. Hydralazine treatment markedly reduced 99mTc-MIBI and 201Tl accumulation in LS180 xenografts; moreover, intratumoural pO2 decreased from 14.5±6.6 mmHg to 7.6±6.2 mmHg. 99mTc-HL91 accumulation in xenografts was markedly increased by hydralazine. In conclusion, hypoxia reduced accumulation of 99mTc-MIBI and 201Tl in tumour cells. Accordingly, hypoxia may be an important factor in terms of the

  17. 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.

  18. Green synthesis of silver nanoparticles for selective toxicity towards cancer cells.

    Science.gov (United States)

    Govindaraju, Kasivelu; Krishnamoorthy, Karthikeyan; Alsagaby, Suliman A; Singaravelu, Ganesan; Premanathan, Mariappan

    2015-12-01

    Therapeutic applications of nanoparticles (NPs) are rapidly increasing for their utility in medicine, especially cancer therapy. The present study investigated the green synthesis of silver NPs (Ag NPs) of 10 nm size using Sargassum vulgare and its preferential ability to kill cancerous human myeloblastic leukemic cells HL60 and cervical cancer cells HeLa as compared with normal peripheral blood mononuclear cells. DNA fragmentation study and annexin V marker fluorescence-activated cell sorting (FACS) analysis revealed the Ag NP-induced cell death is through apoptosis. Transmission electron micrographs have showed the endocytosis of Ag NPs into the nucleus. Ag NPs inhibited the lipid peroxidation-induced reactive oxygen species generation, thus preventing the irradiation-related carcinogenesis. This study suggested that a mechanism underlying the toxicity of Ag NPs towards cancer cells is due to DNA damage and apoptosis. The authors' findings revealed the potential utility of as-prepared Ag NPs in the treatment of cancer as prophylactic agent with antioxidant property and chemotherapeutic agent for their selective toxicity to cancer cells. PMID:26647807

  19. 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.

  20. 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.

  1. 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

  2. Simple synthesis of carbon-11-labeled chromen-4-one derivatives as new potential PET agents for imaging of DNA-dependent protein kinase (DNA-PK) in cancer

    International Nuclear Information System (INIS)

    Carbon-11-labeled chromen-4-one derivatives were synthesized as new potential PET agents for imaging of DNA repair enzyme DNA-dependent protein kinase (DNA-PK) in cancer. The target tracers, X-[11C]methoxy-2-morpholino-4H-chromen-4-ones (X=8, 7, 6, 5; [11C]4a–d), were prepared from their corresponding precursors, X-hydroxy-2-morpholino-4H-chromen-4-ones (X=8, 7, 6, 5; 5a–d), with [11C]CH3OTf through O-[11C]methylation and isolated by a simplified solid-phase extraction (SPE) method using a C-18 Sep-Pak Plus cartridge. The radiochemical yields decay corrected to end of bombardment (EOB), from [11C]CO2, were 40–60%. The specific activity at end of synthesis (EOS) was 185–370 GBq/μmol. - Highlights: ► New chromen-4-one derivatives were synthesized. ► New carbon-11-labeled chromen-4-one derivatives were synthesized. ► Simple solid-phase extraction (SPE) method was employed in radiosynthesis.

  3. 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

  4. 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.

  5. Radioactive tracers in Sedimentology

    International Nuclear Information System (INIS)

    First is given a broad description of the uses of radioactive tracers in Sedimentology. The general method is established, including determinations of probability and standard deviation. Following are determined: the response law of the detector, the minimum mass for statistical detection, and the minimum mass for dynamic detection. The granularity is an important variable in these calculations. Final conclusions are given, and results are compared with existing theories

  6. 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

  7. Design, synthesis, and mechanistic studies of Sansalvamide A derivatives as anti-cancer agents

    OpenAIRE

    Alexander, Leslie Diane

    2012-01-01

    Sansalvamide A (SanA) is a cyclic depsipeptide that was isolated from a marine fungus and demonstrates mid- micromolar anti-cancer activity in the NCI 60-cell line panel. Our laboratory has synthesized over 100 peptide derivatives of this molecule, 5 of which were contributed by the author of this dissertation. The design and solution-phase synthesis of these derivatives is described in Chapter 2. The author was also responsible for attaching PEG-biotin and fluorescein tags to lead SanA deriv...

  8. Synthesis of nanoscale titanium dioxide and its application in cancer therapy

    OpenAIRE

    Wang, Min; Zhou, Zhiguo; Yang, Shiping

    2015-01-01

    As an important inorganic material,titanium dioxide gets more and more attention and is used in various fields,especially in the biomedical field.This paper summarizes the main synthesis methods of titanium dioxide nanomaterial and its applications in cancer therapy area.The titanium dioxide nanomaterial can be prepared by gas,liquid and solid phase methods.Among them,we mainly introduce liquid phase methods including sol-gel method,hydrothermal method,solvothermal,and microemulsion method.We...

  9. Tracers and Tracer Testing: Design, Implementation, Tracer Selection, and Interpretation Methods

    Energy Technology Data Exchange (ETDEWEB)

    G. Michael Shook; Shannon L.; Allan Wylie

    2004-01-01

    Conducting a successful tracer test requires adhering to a set of steps. The steps include identifying appropriate and achievable test goals, identifying tracers with the appropriate properties, and implementing the test as designed. When these steps are taken correctly, a host of tracer test analysis methods are available to the practitioner. This report discusses the individual steps required for a successful tracer test and presents methods for analysis. The report is an overview of tracer technology; the Suggested Reading section offers references to the specifics of test design and interpretation.

  10. A neomorphic cancer cell-specific role of MAGE-A4 in trans-lesion synthesis

    OpenAIRE

    Gao, Yanzhe; Mutter-Rottmayer, Elizabeth; Greenwalt, Alicia M.; Goldfarb, Dennis; Yan, Feng; Yang, Yang; Martinez-Chacin, Raquel C.; Pearce, Kenneth H.; Tateishi, Satoshi; Major, Michael B.; Vaziri, Cyrus

    2016-01-01

    Trans-lesion synthesis (TLS) is an important DNA-damage tolerance mechanism that permits ongoing DNA synthesis in cells harbouring damaged genomes. The E3 ubiquitin ligase RAD18 activates TLS by promoting recruitment of Y-family DNA polymerases to sites of DNA-damage-induced replication fork stalling. Here we identify the cancer/testes antigen melanoma antigen-A4 (MAGE-A4) as a tumour cell-specific RAD18-binding partner and an activator of TLS. MAGE-A4 depletion from MAGE-A4-expressing cancer...

  11. 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

  12. Development of radioisotope tracer technology

    International Nuclear Information System (INIS)

    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)

  13. 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)

  14. 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

  15. Quantitative Proteomics: Measuring Protein Synthesis Using 15N Amino Acids Labeling in Pancreas Cancer Cells

    Science.gov (United States)

    Zhao, Yingchun; Lee, Wai-Nang Paul; Lim, Shu; Go, Vay Liang; Xiao, Jing; Cao, Rui; Zhang, Hengwei; Recker, Robert; Xiao, Gary Guishan

    2010-01-01

    Pancreatic cancer MIA PaCa cells were cultured in the presence and absence of 15N amino acids mixture for 72 hours. During protein synthesis, the incorporation of 15N amino acids results in a new mass isotopomer distribution in protein, which is approximated by the concatenation of two binomial distributions of 13C and 15N. Fraction of protein synthesis (FSR) can thus be determined from the relative intensities of the ‘labeled’ (new) and the ‘unlabeled” (old) spectra. Six prominent spots were picked from 2-D gels of proteins from lysates of cells cultured in 0% (control), and 50% and 33% 15N enriched media. These protein spots were digested and analyzed with MALDI-TOF/TOF. The isotopomer distribution of peptides after labeling can be fully accounted for by the labeled (new) and unlabeled (old) peptides. The ratio of the new and old peptide fractions was determined using multiple regression analysis of the observed spectrum as a linear combination of the expected new and the old spectra. The fractional protein synthesis rates calculated from such ratios of same peptide from cells grown in 50% and 33% 15N amino acid enrichments were comparable to each other. The FSR of these six identified proteins ranged between 44–76%. PMID:19072287

  16. 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

  17. 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.)

  18. 68Ga-AMBA and 18 F-FDG for preclinical PET imaging of breast cancer: effect of tamoxifen treatment on tracer uptake by tumor

    International Nuclear Information System (INIS)

    Introduction: AMBA is a bombesin analogue that binds to GRPr. In a mouse model of estrogen-dependent human breast cancer, we tested whether 68Ga-AMBA can be used for PET detection of GRPr-expressing tumors and could be more accurate than 18F-FDG to monitor tumor response to hormone therapy. Methods: The radiolabeling of 68Ga-AMBA was automated using a R and D Synchrom module. ZR75-1, a breast cancer cell line, was xenografted in nude mice. 68Ga-AMBA tumor uptake was compared with that of 18F-FDG before and after treatment with tamoxifen. Results: AMBA was 68Ga-radiolabelled in 30 min with 95.3% yield and purity ≥ 98%. Prior to treatment, 68Ga-AMBA was highly concentrated into tumors (tumor to non-tumor ratio = 2.4 vs. 1.3 with 18F-FDG). With tamoxifen treatment (n = 6) 68Ga-AMBA uptake plateaued after 1 week and decreased after 2 weeks, with a significant reduction compared to controls (n = 4). In contrast the effect of tamoxifen treatment could not be appreciated using 18F-FDG. Conclusions: 68Ga-AMBA appeared better than 18F-FDG to visualize and monitor the response to hormone treatment in this breast cancer model

  19. 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.

  20. The value of PET/CT with FES or FDG tracers in metastatic breast cancer: a computer simulation study in ER-positive patients

    OpenAIRE

    Koleva-Kolarova, R.G.; Greuter, M. J. W.; van Kruchten, M; Vermeulen, K.M.; Feenstra, T; Buskens, E; Glaudemans, A. W. J. M.; de Vries, E F J; de Vries, E G E; Hospers, G A P; de Bock, G H

    2015-01-01

    Background: The aim of this study was to evaluate the effect on the number of performed biopsies and costs associated with implementing positron emission tomography (PET) and computed tomography (PET/CT) with 16α-[18F]fluoro-17β-oestradiol (FES) or 2-[18F]fluoro-2-deoxy-D-glucose (FDG) as an upfront imaging test for diagnosing metastatic breast cancer (MBC) in comparison with the standard work-up in oestrogen receptor-positive women with symptoms. Methods: A published computer simulation mode...

  1. 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...

  2. Synthesis and characterization of near IR fluorescent albumin nanoparticles for optical detection of colon cancer

    International Nuclear Information System (INIS)

    Near IR (NIR) fluorescent human serum albumin (HSA) nanoparticles hold great promise as contrast agents for tumor diagnosis. HSA nanoparticles are considered to be biocompatible, non-toxic and non-immunogenic. In addition, NIR fluorescence properties of these nanoparticles are important for in vivo tumor diagnostics, with low autofluorescence and relatively deep penetration of NIR irradiation due to low absorption of biomatrices. The present study describes the synthesis of new NIR fluorescent HSA nanoparticles, by entrapment of a NIR fluorescent dye within the HSA nanoparticles, which also significantly increases the photostability of the dye. Tumor-targeting ligands such as peanut agglutinin (PNA) and anti-carcinoembryonic antigen antibodies (anti-CEA) were covalently conjugated to the NIR fluorescent albumin nanoparticles, increasing the potential fluorescent signal in tumors with upregulated corresponding receptors. Specific colon tumor detection by the NIR fluorescent HSA nanoparticles was demonstrated in a chicken embryo model and a rat model. In future work we also plan to encapsulate cancer drugs such as doxorubicin within the NIR fluorescent HSA nanoparticles for both colon cancer imaging and therapy. - Highlights: ► Near IR human serum albumin nanoparticles were synthesized and characterized. ► Nanoparticles were shown to be physically and chemically stable and photostable. ► Tumor-targeting ligands were covalently conjugated to the nanoparticles. ► Specific colon cancer tumor detection was demonstrated in chicken-embryo and rat models.

  3. 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

  4. 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.

  5. Synthesis and characterization of near IR fluorescent albumin nanoparticles for optical detection of colon cancer

    Energy Technology Data Exchange (ETDEWEB)

    Cohen, Sarit; Pellach, Michal [Department of Chemistry, Bar-Ilan Institute of Nanotechnology and Advanced Materials, Bar-Ilan University, Ramat-Gan 52900 (Israel); Kam, Yossi [Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, P.O. Box 12065, Jerusalem 91120 (Israel); Grinberg, Igor; Corem-Salkmon, Enav [Department of Chemistry, Bar-Ilan Institute of Nanotechnology and Advanced Materials, Bar-Ilan University, Ramat-Gan 52900 (Israel); Rubinstein, Abraham [Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, P.O. Box 12065, Jerusalem 91120 (Israel); Margel, Shlomo, E-mail: shlomo.margel@mail.biu.ac.il [Department of Chemistry, Bar-Ilan Institute of Nanotechnology and Advanced Materials, Bar-Ilan University, Ramat-Gan 52900 (Israel)

    2013-03-01

    Near IR (NIR) fluorescent human serum albumin (HSA) nanoparticles hold great promise as contrast agents for tumor diagnosis. HSA nanoparticles are considered to be biocompatible, non-toxic and non-immunogenic. In addition, NIR fluorescence properties of these nanoparticles are important for in vivo tumor diagnostics, with low autofluorescence and relatively deep penetration of NIR irradiation due to low absorption of biomatrices. The present study describes the synthesis of new NIR fluorescent HSA nanoparticles, by entrapment of a NIR fluorescent dye within the HSA nanoparticles, which also significantly increases the photostability of the dye. Tumor-targeting ligands such as peanut agglutinin (PNA) and anti-carcinoembryonic antigen antibodies (anti-CEA) were covalently conjugated to the NIR fluorescent albumin nanoparticles, increasing the potential fluorescent signal in tumors with upregulated corresponding receptors. Specific colon tumor detection by the NIR fluorescent HSA nanoparticles was demonstrated in a chicken embryo model and a rat model. In future work we also plan to encapsulate cancer drugs such as doxorubicin within the NIR fluorescent HSA nanoparticles for both colon cancer imaging and therapy. - Highlights: Black-Right-Pointing-Pointer Near IR human serum albumin nanoparticles were synthesized and characterized. Black-Right-Pointing-Pointer Nanoparticles were shown to be physically and chemically stable and photostable. Black-Right-Pointing-Pointer Tumor-targeting ligands were covalently conjugated to the nanoparticles. Black-Right-Pointing-Pointer Specific colon cancer tumor detection was demonstrated in chicken-embryo and rat models.

  6. Matrix Analysis of Tracer Transport

    CERN Document Server

    Mills, Peter

    2015-01-01

    We review matrix methods as applied to tracer transport. Because tracer transport is linear, matrix methods are an ideal fit for the problem. In particular, solutions of linear, first-order systems of ordinary differential equations (ODEs) are reviewed as well as special properties of these solutions. Detailed derivations are included

  7. 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)

  8. Effect of different BNCT protocols on DNA synthesis in precancerous and normal tissues in an experimental model of oral cancer

    International Nuclear Information System (INIS)

    We previously reported the therapeutic success of different BNCT protocols in the treatment of oral cancer, employing the hamster cheek pouch model. The aim of the present study was to evaluate the effect of these BNCT protocols on DNA synthesis in precancerous and normal tissue in this model and assess the potential lag in the development of second primary tumors in precancerous tissue. The data are relevant to potential control of field cancerized tissue and tolerance of normal tissue. We evaluated DNA synthesis in precancerous and normal pouch tissue 1-30 days post-BNCT mediated by BPA, GB-10 or BPA + GB-10 employing incorporation of bromo-deoxyuridine as an end-point. The BNCT-induced potential lag in the development of second primary tumors in precancerous tissue was monitored. A drastic, statistically significant reduction in DNA synthesis occurred in pacancerous tissue as early as 1 day post-BNCT and was sustained at virtually all time points until 30 days post-BNCT for all protocols. The histological categories evaluated individually within precancerous tissue (dysplasia, hyperplasia and NUMF [no unusual microscopic features]) responded similarly. DNA synthesis in normal tissue treated with BNCT oscillated around the very low pre-treatment values. A BNCT-induced lag in the development of second primary tumors was observed. BNCT induced a drastic fall in DNA synthesis in precancerous tissue that would be associated to the observed lag in the development of second primary tumors. The minimum variations in DNA synthesis in BNCT-treated normal tissue would correlate with the absence of normal tissue radiotoxicity. The present data would contribute to optimize therapeutic efficacy in the treatment of field-cancerized areas. (author)

  9. 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

  10. 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.

  11. Proceedings of the atmospheric tracers and tracer application workshop

    International Nuclear Information System (INIS)

    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 13C18O2, 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

  12. Synthesis and secretion of platelet-derived growth factor by human breast cancer cell lines

    International Nuclear Information System (INIS)

    The authors report that human breast cancer cells secrete a growth factor that is biologically and immunologically similar to platelet-derived growth factor (PDGF). Serum-free medium conditioned by estrogen-independent MDA-MB-231 or estrogen-dependent MCF-7 cells contains a mitogenic or competence activity that is capable of inducing incorporation of [3H] thymidine into quiescent Swiss 3T3 cells in the presence of platelet-poor plasma. Like authentic PDGF, the PDGF-like activity produced by breast cancer cells is stable after acid and heat treatment (950C) and inhibited by reducing agents. The mitogenic activity comigrates with a material of ≅30 kDa on NaDodSO4/polyacrylamide gels. Immunoprecipitation with PDGF antiserum of proteins from metabolically labeled cell lysates and conditioned medium followed by analysis on nonreducing NaDodSO4/polyacrylamide gels identified proteins of 30 and 34 kDa. Upon reduction, the 30- and 34-kDa bands were converted to 15- and 16-kDa bands suggesting that the immunoprecipitated proteins were made up of two disulfide-linked polypeptides similar to PDGF. Hybridization studies with cDNA probes for the A chain PDGF and the B chain of PDGF/SIS identified transcripts for both PDGF chains in the MCF-7 and MDA-MB-231 cells. The data summarized above provide conclusive evidence for the synthesis and hormonally regulated secretion of a PDGF-like mitogen by breast carcinoma cells. Production of a PDGF-like growth factor by breast cancer cell lines may be important in mediating paracrine stimulation of tumor growth

  13. Novel tracer for radiation treatment planning; Welche neuen PET-Tracer braucht die Strahlentherapie?

    Energy Technology Data Exchange (ETDEWEB)

    Schwarzenboeck, S.; Krause, B.J. [Rostock Univ. (Germany). Klinik fuer Nuklearmedizin; Herrmann, K.; Gaertner, F.; Souvatzoglou, M. [Technische Univ. Muenchen (Germany). Klinik fuer Nuklearmedizin; Klaesner, B. [Klinikum Bogenhausen, Muenchen (Germany). Inst. fuer Radiologie und Nuklearmedizin

    2011-07-15

    PET and PET/CT with innovative tracers gain increasing importance in diagnosis and therapy management, and radiation treatment planning in radio-oncology besides the widely established FDG. The introduction of [{sup 18}F]Fluorothymidine ([{sup 18}F]FLT) as marker of proliferation, [{sup 18}F]Fluoromisonidazole ([{sup 18}F]FMISO) and [{sup 18}F]Fluoroazomycin-Arabinoside ([{sup 18}F]FAZA) as tracer of hypoxia, [{sup 18}F]Fluoroethyltyrosine ([{sup 18}F]FET) and [{sup 11}C]Methionine for brain tumour imaging, [{sup 68}Ga]DOTATOC for somatostatin receptor imaging, [{sup 18}F]FDOPA for dopamine synthesis and radioactively labeled choline derivatives for imaging phospholipid metabolism have opened novel approaches to tumour imaging. Some of these tracers have already been implemented into radio-oncology: Amino acid PET and PET/CT have the potential to optimise radiation treatment planning of brain tumours through accurate delineation of tumour tissue from normal tissue, necrosis and edema. Hypoxia represents a major therapeutic problem in radiation therapy. Hypoxia imaging is very attractive as it may allow to increase the dose in hypoxic tumours potentially allowing for a better tumour control. Advances in hybrid imaging, i.e. the introduction of MR/PET, may also have an impact in radio-oncology through synergies related to the combination of molecular signals of PET and a high soft tissue contrast of MRI as well as functional MRI capabilities. (orig.)

  14. Near source tracers at Hanford

    International Nuclear Information System (INIS)

    Atmospheric tracer techniques are reviewed, with emphasis on the Hanford inert gas krypton-85 field technique. This technique is considerably more sophisticated than the visible and particulate tracer techniques. The krypton technique develops histories of concentration at up to 128 field locations; the particulate techniques generate only bulk time integrated samples. The krypton dispersal technique permits release of either a plume or a true puff; the particulate techniques permit continuous releases, but only approximations of puffs through short continuous releases. The Hanford krypton-85 inert gas system offers the advantages of an inert gas tracer, permits release of either puffs or plumes, and presents histories of concentration as opposed to only time-integrated concentrations. However, the approach used has the disadvantages of being usable at only short distances, is a relatively expensive system to deploy and maintain, and is restricted as to locations where it may be used due to the radioactive nature of the tracer

  15. Synthesis and anti-cancer activity of 1,4-disubstituted imidazo[4,5-c]quinolines.

    Science.gov (United States)

    Thigulla, Yadagiri; Akula, Mahesh; Trivedi, Prakruti; Ghosh, Balaram; Jha, Mukund; Bhattacharya, Anupam

    2016-01-21

    The synthesis and anti-cancer activity evaluation of fused imidazoquinoline compounds is reported in this paper. Yb(OTf)3 has been utilized as a catalyst for the synthesis of 1,4-diaryl substituted imidazo[4,5-c]quinolines via a modified Pictet-Spengler approach. The desired imidazole ring was synthesized from imines using TosMIC (toluenesulfonylmethyl isocyanide) and subsequently functionalized at the C-4 position yielding an imidazoquinoline skeleton. Importantly, the final step was carried out without the aid of any prefunctionalization to obtain the resultant compounds in good yields. The synthesized compounds, when screened for anti-cancer activity, revealed the highest activity with 4-(2-bromophenyl)-1-phenyl-1H-imidazo[4,5-c]quinoline (IC50: 103.3 μM). PMID:26592542

  16. 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

  17. Serine Metabolism Supports the Methionine Cycle and DNA/RNA Methylation through De Novo ATP Synthesis in Cancer Cells.

    Science.gov (United States)

    Maddocks, Oliver D K; Labuschagne, Christiaan F; Adams, Peter D; Vousden, Karen H

    2016-01-21

    Crosstalk between cellular metabolism and the epigenome regulates epigenetic and metabolic homeostasis and normal cell behavior. Changes in cancer cell metabolism can directly impact epigenetic regulation and promote transformation. Here we analyzed the contribution of methionine and serine metabolism to methylation of DNA and RNA. Serine can contribute to this pathway by providing one-carbon units to regenerate methionine from homocysteine. While we observed this contribution under methionine-depleted conditions, unexpectedly, we found that serine supported the methionine cycle in the presence and absence of methionine through de novo ATP synthesis. Serine starvation increased the methionine/S-adenosyl methionine ratio, decreasing the transfer of methyl groups to DNA and RNA. While serine starvation dramatically decreased ATP levels, this was accompanied by lower AMP and did not activate AMPK. This work highlights the difference between ATP turnover and new ATP synthesis and defines a vital function of nucleotide synthesis beyond making nucleic acids.

  18. Accounting for pharmacokinetic differences in dual-tracer receptor density imaging

    Science.gov (United States)

    Tichauer, K. M.; Diop, M.; Elliott, J. T.; Samkoe, K. S.; Hasan, T.; St. Lawrence, K.; Pogue, B. W.

    2014-05-01

    Dual-tracer molecular imaging is a powerful approach to quantify receptor expression in a wide range of tissues by using an untargeted tracer to account for any nonspecific uptake of a molecular-targeted tracer. This approach has previously required the pharmacokinetics of the receptor-targeted and untargeted tracers to be identical, requiring careful selection of an ideal untargeted tracer for any given targeted tracer. In this study, methodology capable of correcting for tracer differences in arterial input functions, as well as binding-independent delivery and retention, is derived and evaluated in a mouse U251 glioma xenograft model using an Affibody tracer targeted to epidermal growth factor receptor (EGFR), a cell membrane receptor overexpressed in many cancers. Simulations demonstrated that blood, and to a lesser extent vascular-permeability, pharmacokinetic differences between targeted and untargeted tracers could be quantified by deconvolving the uptakes of the two tracers in a region of interest devoid of targeted tracer binding, and therefore corrected for, by convolving the uptake of the untargeted tracer in all regions of interest by the product of the deconvolution. Using fluorescently labeled, EGFR-targeted and untargeted Affibodies (known to have different blood clearance rates), the average tumor concentration of EGFR in four mice was estimated using dual-tracer kinetic modeling to be 3.9 ± 2.4 nM compared to an expected concentration of 2.0 ± 0.4 nM. However, with deconvolution correction a more equivalent EGFR concentration of 2.0 ± 0.4 nM was measured.

  19. Synthesis of structurally diverse benzosuberene analogues and their biological evaluation as anti-cancer agents.

    Science.gov (United States)

    Tanpure, Rajendra P; George, Clinton S; Strecker, Tracy E; Devkota, Laxman; Tidmore, Justin K; Lin, Chen-Ming; Herdman, Christine A; Macdonough, Matthew T; Sriram, Madhavi; Chaplin, David J; Trawick, Mary Lynn; Pinney, Kevin G

    2013-12-15

    Diversely functionalized, fused aryl-alkyl ring systems hold a prominent position as well-established molecular frameworks for a variety of anti-cancer agents. The benzosuberene (6,7 fused, also referred to as dihydro-5H-benzo[7]annulene and benzocycloheptene) ring system has emerged as a valuable molecular core component for the development of inhibitors of tubulin assembly, which function as antiproliferative anti-cancer agents and, in certain cases, as vascular disrupting agents (VDAs). Both a phenolic-based analogue (known as KGP18, compound 39) and its corresponding amine-based congener (referred to as KGP156, compound 45), which demonstrate strong inhibition of tubulin assembly (low micromolar range) and potent cytotoxicity (picomolar range for KGP18 and nanomolar range for KGP156) are noteworthy examples of such benzosuberene-based compounds. In order to extend the structure-activity relationship (SAR) knowledge base related to benzosuberene anti-cancer agents, a series of eleven analogues (including KGP18) were prepared in which the methoxylation pattern on the pendant aryl ring as well as functional group incorporation on the fused aryl ring were varied. The synthetic approach to these compounds featured a sequential Wittig olefination, reduction, Eaton's reagent-mediated cyclization strategy to achieve the core benzosuberone intermediate, and represented a higher-yielding synthesis of KGP18 (which we prepared previously through a ring-expansion strategy). Incorporation of a fluorine or chlorine atom at the 1-position of the fused aryl ring or replacement of one of the methoxy groups with hydrogen (on the pendant aryl ring of KGP18) led to benzosuberene analogues that were both strongly inhibitory against tubulin assembly (IC50 approximately 1.0 μM) and strongly cytotoxic against selected human cancer cell lines (for example, GI50=5.47 nM against NCI-H460 cells with fluoro-benzosuberene analogue 37). A water-soluble phosphate prodrug salt of KGP18

  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. Nanosized tamoxifen-porphyrin-glucose [TPG] conjugate: novel selective anti-breast-cancer agent, synthesis and in vitro evaluations.

    Science.gov (United States)

    Amanlou, Massoud; Heidari, Zahra; Siadat, Seyed Davar; Aghasadeghi, Mohammad Reza; Ghorbani, Masoud; Ebrahimi, Seyed Esmaeil Sadat; Sadat, Seyed Mehdi; Hajmohammadi, Mehdi; Arabzadeh, Ali Jabbari; Hekmat, Soheila; Alaei-Beirami, Mahmood; Saraji, Alireza Azizi; Moghaddam, Hadi Fathi; Alavidjeh, Mohammad Shafiee; Delbaz, Seyed Ali; Dashtbani-Roozbehani, Abolfazl; Ardestani, Mehdi Shafiee

    2013-06-01

    Tumor and especially breast cancer is among the most common causes of death worldwide. Finding novel nanosized therapeutic compounds have important role to decrease the chance of death and increase the survival. Cancer cells are highly attractive to glucose [with a nanosize bimolecular structure 1nm] as an energy source more than normal cell and nanosized therapeutics due to possessing different pharmacokinetic and pharmacodynamic have advantageous over classical dosage forms in cancer therapy. The aim of the study was to synthesize Glucosamin-Porphyrin-Tamoxifen [TPG] nanosized complex as a novel selective biocompatible anti breast cancer agent. After the synthesis procedure, this complex was purified and then tested In Vitro on breast cancer cells [MCF-7] in the absence or presence of the red light and found totally successful. The results showed a good anti breast cancer activity mediated by the activation of TNF-α and necrosis/apoptosis pathways for the nanosized complex with no alteration effects on blood PT/APTT and glucose or hexokinase levels/ activity. TPG nanoconjugate seems to be very good opponents to current anti breast cancer drugs and needs to be further investigated in near future.

  2. Evaluation of 4-[{sup 18}F]fluorobenzoyl-FALGEA-NH{sub 2} as a positron emission tomography tracer for epidermal growth factor receptor mutation variant III imaging in cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lund Denholt, Charlotte, E-mail: charlotte.lund.denholt@rh.regionh.d [Department of Clinical Physiology, Nuclear Medicine and PET, Copenhagen University Hospital, Rigshospitalet, 2100 Copenhagen O (Denmark); Binderup, Tina [Department of Clinical Physiology, Nuclear Medicine and PET, Copenhagen University Hospital, Rigshospitalet, 2100 Copenhagen O (Denmark); Cluster for Molecular Imaging, Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen N (Denmark); Stockhausen, Marie-Therese; Skovgaard Poulsen, Hans [Department of Radiation Biology, Copenhagen University Hospital Rigshospitalet, 2100 Copenhagen O (Denmark); Spang-Thomsen, Mogens [Institute of Molecular Pathology, University of Copenhagen, 2200 Copenhagen N (Denmark); Hansen, Paul Robert [IGM-Bioorganic Chemistry, Faculty of Life Science, University of Copenhagen, 1871 Frederiksberg C (Denmark); Gillings, Nic [Department of Clinical Physiology, Nuclear Medicine and PET, Copenhagen University Hospital, Rigshospitalet, 2100 Copenhagen O (Denmark); Kjaer, Andreas [Department of Clinical Physiology, Nuclear Medicine and PET, Copenhagen University Hospital, Rigshospitalet, 2100 Copenhagen O (Denmark); Cluster for Molecular Imaging, Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen N (Denmark)

    2011-05-15

    Introduction: This study describes the radiosynthesis, in vitro and in vivo evaluation of the novel small peptide radioligand, 4-[{sup 18}F]fluorobenzoyl-Phe-Ala-Leu-Gly-Glu-Ala-NH{sub 2,} ([{sup 18}F]FBA-FALGEA-NH{sub 2}) as a positron emission tomography (PET) tracer for imaging of the cancer specific epidermal growth factor receptor (EGFR) variant III mutation, EGFRvIII. Methods: For affinity, stability and PET measurements, H-FALGEA-NH{sub 2} was radiolabelled using 4-[{sup 18}F]fluorobenzoic acid ([{sup 18}F]FBA). The binding affinity of ([{sup 18}F]FBA)-FALGEA-NH{sub 2} was measured on EGFRvIII expressing cells, NR6M. Stability studies in vitro and in vivo were carried out in blood plasma from nude mice. PET investigations of [{sup 18}F]FBA-FALGEA-NH{sub 2} were performed on a MicroPET scanner, using seven nude mice xenografted subcutaneously with human glioblastoma multiforme (GBM) tumours, expressing the EGFRvIII in its native form, and five nude mice xenografted subcutaneously with GBM tumours lacking EGFRvIII expression. Images of [{sup 18}F]FDG were also obtained for comparison. The mice were injected with 5-10 MBq of the radiolabelled peptide or [{sup 18}F]FDG. Furthermore, the gene expression of EGFRvIII in the tumours was determined using quantitative real-time PCR. Results: Radiolabelling and purification was achieved within 180 min, with overall radiochemical yields of 2.6-9.8% (decay-corrected) and an average specific radioactivity of 6.4 GBq/{mu}mol. The binding affinity (K{sub d}) of [{sup 18}F]FBA-FALGEA-NH{sub 2} to EGFRvIII expressing cells was determined to be 23 nM. The radiolabelled peptide was moderately stable in the plasma from nude mice where 53% of the peptide was intact after 60 min of incubation in plasma but rapidly degraded in vivo, where no intact peptide was observed in plasma 5 min post-injection. The PET imaging showed that [{sup 18}F]FBA-FALGEA-NH{sub 2} accumulated preferentially in the human GBM xenografts which expressed

  3. 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.

  4. Tracers for monitoring the activity of sodium/glucose cotransporters in health and disease

    Energy Technology Data Exchange (ETDEWEB)

    Wright, Ernest M; Barrio, Jorge R; Hirayama, Bruce A; Kepe, Vladimir

    2014-09-30

    Radiolabeled tracers for sodium/glucose cotransporters (SGLTs), their synthesis, and their use are provided. The tracers are methyl or ethyl pyranosides having an equatorial hydroxyl group at carbon-2 and a C 1 preferred conformation, radiolabeled with .sup.18F, .sup.123I, or .sup.124I, or free hexoses radiolabeled with .sup.18F, .sup.123I, or .sup.124. Also provided are in vivo and in vitro techniques for using these and other tracers as analytical and diagnostic tools to study glucose transport, in health and disease, and to evaluate therapeutic interventions.

  5. Radioactive tracers in the sea

    International Nuclear Information System (INIS)

    Artificial radionuclides introduced to the oceans during the last four decades have proved invaluable tools for study of many processes in marine water columns and sediments. Both global and close-in fallout of radioactivity from atmospheric nuclear weapons testing have distributed these radionuclides widely, and in amounts sufficient to be useful as tracers. An additional source of considerable significance and tracer potential comes from coastal discharges of European nuclear fuel reprocessing wastes. The nature of these sources, types and amounts of radionuclides introduced and the time histories of their introduction generate a variety of tracer distributions which illuminate a broad spectrum of physical and chemical processes active over a wide range of timescales. Depending on their respective chemistries, artificial radionuclides have been demonstrated to exhibit both conservative and non-conservative properties in the oceans. Some examples are given of the uses made of soluble, conservative tracers for the study of oceanic transport processes and of non-conservative tracers for studies of processes which move them to, and mix them within, marine sediments. Sampling and measurement techniques which have been used in these studies are described

  6. Synthesis and cellular uptake of folic acid-conjugated cellulose nanocrystals for cancer targeting.

    Science.gov (United States)

    Dong, Shuping; Cho, Hyung Joon; Lee, Yong Woo; Roman, Maren

    2014-05-12

    Elongated nanoparticles have recently been shown to have distinct advantages over spherical ones in targeted drug delivery applications. In addition to their oblong geometry, their lack of cytotoxicity and numerous surface hydroxyl groups make cellulose nanocrystals (CNCs) promising drug delivery vectors. Herein we report the synthesis of folic acid-conjugated CNCs for the targeted delivery of chemotherapeutic agents to folate receptor-positive cancer cells. Folate receptor-mediated cellular binding/uptake of the conjugate was demonstrated on human (DBTRG-05MG, H4) and rat (C6) brain tumor cells. Folate receptor expression of the cells was verified by immunofluorescence staining. Cellular binding/uptake of the conjugate by DBTRG-05MG, H4, and C6 cells was 1452, 975, and 46 times higher, respectively, than that of nontargeted CNCs. The uptake mechanism was determined by preincubation of the cells with the uptake inhibitors chlorpromazine or genistein. DBTRG-05MG and C6 cells internalized the conjugate primarily via caveolae-mediated endocytosis, whereas H4 cells internalized the conjugate primarily via clathrin-mediated endocytosis. PMID:24716601

  7. 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.)

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

    International Nuclear Information System (INIS)

    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

  9. Synthesis and Biological Evaluation of a Novel Pentagastrin- Toxin Conjugate Designed for a Targeted Prodrug Monotherapy of Cancer

    Directory of Open Access Journals (Sweden)

    Ingrid Schuberth

    2008-05-01

    Full Text Available A novel carbamate prodrug 2 containing a pentagastrin moiety was synthesized. 2 was designed as a detoxified analogue of the highly cytotoxic natural antibiotic duocarmycin SA (1 for the use in a targeted prodrug monotherapy of cancers expressing cholecystokinin (CCK-B/gastrin receptors. The synthesis of prodrug 2 was performed using a palladium-catalyzed carbonylation of bromide 6, followed by a radical cyclisation to give the pharmacophoric unit 10, coupling of 10 to the DNA-binding subunit 15 and transformation of the resulting seco-drug 3b into the carbamate 2 via addition of a pentagastrin moiety.

  10. 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

  11. 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.

  12. 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

  13. Strategic fit analysis - RW tracers

    OpenAIRE

    Berea Bellon, Carlos Adolfo

    2005-01-01

    This paper analyses, RW Tracers, a company dedicated to tracing lost individuals, to determine how to improve its performance since expected sales growth and profitability margin have yet to be met. The company's strategy is examined to determine if the company meets the criteria of strategic fit. To add context, an Industry Analysis is conducted to determine the Key Success Factors of the tracing industry. These Key Success Factors are then linked to the Industry Value Chain to build a model...

  14. 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.

  15. 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.

  16. Phase I and pharmacokinetic study of the polyamine synthesis inhibitor SAM486A in combination with 5-fluorouracil/leucovorin in metastatic colorectal cancer

    NARCIS (Netherlands)

    L. van Zuylen; C. Mueller; J. Verweij (Jaap); J.A. Ledermann; J. Bridgewater; A. Sparreboom (Alex); F.A.L.M. Eskens (Ferry); P. de Bruijn (Peter); I. Sklenar; A.S.Th. Planting (André); L. Choi; D. Bootle

    2004-01-01

    textabstractPURPOSE: The purpose of our study was to determine the maximum-tolerated dose, dose-limiting toxicity, safety profile, and pharmacokinetics of the polyamine synthesis inhibitor SAM486A given in combination with 5-fluorouracil/leucovorin (5-FU/LV) in cancer patients. EXP

  17. 68Ga-PSMA PET/CT False-Positive Tracer Uptake in Paget Disease.

    Science.gov (United States)

    Sasikumar, Arun; Joy, Ajith; Nanabala, Raviteja; Pillai, M R A; T A, Hari

    2016-10-01

    65-year-old man with left-sided pelvic pain on evaluation was found to have features suggestive of either Paget disease or prostatic bone metastasis of the left hemipelvis based on Tc-MDP bone scan and MRI. Ga-PSMA PET/CT to assess the possibility of primary prostate cancer and if present to stage it helped to rule out prostate cancer because of absence of focal abnormal increased tracer uptake in the prostate gland. However, false-positive tracer uptake was noted in the left hemipelvis, which was subject to biopsy and histopathologically proven to be Paget disease involvement. PMID:27556797

  18. Synthesis and iodine-125 labelling of glucuronide compounds for combined chemo- and radiotherapy of cancer

    Energy Technology Data Exchange (ETDEWEB)

    Unak, T.; Ongun, B. [Ege Univ., Izmir (Turkey). Dept. of Chemistry; Unak, P. [Ege Univ., Izmir (Turkey). Inst. of Nuclear Sciences; Duman, Y. [Ege Univ., Izmir (Turkey). Dept. of Nuclear Medicine

    1997-06-01

    Some types of cancer cells have high levels of beta-glucuronidase activity. This enzyme is able to deglucuronidate a variety of glucuronie derivatives on the cell membrane. Either O- or N-glucuronides can be selectively incorporated into the cancer cells. If the aglycone is cytotoxic, the glucuronide can potentially be used as a selective anti-cancer drug in cancers with high levels of beta-glucuronidase activity. Nevertheless, in vitro studies carried out by various investigators have shown that the cytotoxicities of several glucuronides in cancer cells are not sufficiently high for their use as effective anti-cancer drugs. For this reason, we have synthesized glucuronide compounds radiolabelled with iodine-125 combining the radiotoxicity of this Auger electron emitter with the chemotoxicity of the aglycone portion of the glucuronide. (author).

  19. 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.

  20. Petroleum characterization by perfluorocarbon tracers

    Energy Technology Data Exchange (ETDEWEB)

    Senum, G.I.; Fajer, R.W. (Brookhaven National Lab., Upton, NY (United States)); Harris, B.R. Jr. (USDOE Naval Petroleum Reserves in California, Tupman, CA (United States)); DeRose, W.E. (Bechtel Petroleum Operations, Inc., Tupman, CA (United States)); Ottaviani, W.L. (Chevron U.S.A., Inc., Bakersfield, CA (United States))

    1992-02-01

    Perfluorocarbon tracers (PFTs), a class of six compounds, were used to help characterize the Shallow Oil Zone (SOZ) reservoir at the Naval Petroleum Reserve in California (NPRC) at Elk Hills. The SOZ reservoir is undergoing a pilot gas injection program to assess the technical feasibility and economic viability of injecting gas into the SOZ for improved oil recovery. PFTs were utilized in the pilot gas injection to qualitatively assess the extent of the pilot gas injection so as to determine the degree of gas containment within the SOZ reservoir.

  1. 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...

  2. Use of artificial tracers in hydrology

    International Nuclear Information System (INIS)

    The IAEA has convened an Advisory Group Meeting with the following objectives: To define the role of artificial radioactive tracers for water tracing in comparison with other non-radioactive tracers. To evaluate the real needs of artificial radioactive tracers in hydrology. To identify the fields for which artificial radioactive tracers are useful as well as those in which they can be substituted by other tracers. To discuss the strategy to be adopted to overcome the difficulties derived from the restrictions on the use of radioactive tracers in hydrology. The meeting was held at IAEA Headquarters from 19 to 22 March 1990, and was attended by 30 participants from 15 Member States. The conclusions and recommendations are that the use of artificial radioactive tracers should be restricted to cases where other tracers cannot be used or do not provide the same quality of information. Tritium, iodine-131, bromine-82, chromium-51 in the form of Cr-EDTA, technetium-99m obtained from 99Mo-generators and gold-198 as an adsorbable tracer are, practically, the only radionuclides used for water tracing. The use of other radionuclides for this purpose does not appear to be necessary, possible and/or convenient. Refs, figs and tabs

  3. Tracer a application in marine outfall studies

    International Nuclear Information System (INIS)

    The applicability of radioactive and fluorescent tracers for field studies to predict or investigate waste water transport and dispersion from marine outfalls is evaluated. The application of either instantaneous or continuous tracer release, 'in situ' detection of tracers and data processing are considered. The necessity of a combined use of tracer techniques and conventional hydrographic methods for a statistical prediction of transport and dillution of waste water are pointed out. A procedure to determine an outlet distance from the coast, which satisfy bathing water criteria is outlined. (M.A.)

  4. Synthesis and Characterization of Inhalable Flavonoid Nanoparticle for Lung Cancer Cell Targeting.

    Science.gov (United States)

    Lee, Wing-Hin; Loo, Ching-Yee; Ong, Hui-Xin; Traini, Daniela; Young, Paul M; Rohanizadeh, Ramin

    2016-02-01

    Current cancer treatments are not adequate to cure cancer disease, as most chemotherapeutic drugs do not differentiate between cancerous and non-cancerous cells; which lead to systemic toxicity and adverse effects. We have developed a promising approach to deliver a potential anti-cancer compound (curcumin) for lung cancer treatment through pulmonary delivery. Three different sizes of curcumin micellar nanoparticles (Cur-NPs) were fabricated and their cytotoxicity effects (proliferation, apoptosis, cell cycle progression) were evaluated against non-small-cell lung cancer, human lung carcinoma (A549) and human lung adenocarcinoma (Calu-3). The in vitro cytotoxicity assay showed that Cur-NPs were more effective to kill lung cancer cells compared to DMSO-solubilised raw curcumin. The potency of the anti-cancer killing activities was size-dependent. Both raw curcumin and Cur-NPs were not toxic to healthy lung cells (BEAS-2B). Smaller Cur-NPs accumulated within nucleus, membrane and cytoplasm. Cur-NPs also induced apoptosis and caused G2/M arrest in both A549 and Calu-3 cell lines. Compared to raw curcumin, Cur-NPs were more effective in suppressing the expression of the inflammatory marker, Interleukin-8 (IL8). The aerosol performance of Cur-NPs was characterized using the next generation impactor (NGI). All Cur-NPs showed promising aerosolization property with mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD) ranging between 4.8-5.2 and 2.0-2.1, respectively. This study suggests that inhaled curcumin nanoparticles could potentially be used for lung cancer treatment with minimal side effects. PMID:27305771

  5. 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

  6. 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.

  7. Nucleotide excision repair DNA synthesis by excess DNA polymerase beta: a potential source of genetic instability in cancer cells.

    Science.gov (United States)

    Canitrot, Y; Hoffmann, J S; Calsou, P; Hayakawa, H; Salles, B; Cazaux, C

    2000-09-01

    The nucleotide excision repair pathway contributes to genetic stability by removing a wide range of DNA damage through an error-free reaction. When the lesion is located, the altered strand is incised on both sides of the lesion and a damaged oligonucleotide excised. A repair patch is then synthesized and the repaired strand is ligated. It is assumed that only DNA polymerases delta and/or epsilon participate to the repair DNA synthesis step. Using UV and cisplatin-modified DNA templates, we measured in vitro that extracts from cells overexpressing the error-prone DNA polymerase beta exhibited a five- to sixfold increase of the ultimate DNA synthesis activity compared with control extracts and demonstrated the specific involvement of Pol beta in this step. By using a 28 nt gapped, double-stranded DNA substrate mimicking the product of the incision step, we showed that Pol beta is able to catalyze strand displacement downstream of the gap. We discuss these data within the scope of a hypothesis previously presented proposing that excess error-prone Pol beta in cancer cells could perturb the well-defined specific functions of DNA polymerases during error-free DNA transactions. PMID:10973926

  8. 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.

  9. 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. PMID:24900701

  10. 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.

  11. 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.

  12. 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...

  13. Effects of the source of energy and minerals on microbial protein synthesis in rumen using 35S as indicator. Part of a coordinated programme on tracer techniques in studies on the use of non-protein nitrogen in ruminants

    International Nuclear Information System (INIS)

    Part I. The effect of the nature of carbohydrates and minerals on microbial growth in vitro was studied in vitro to intensify rumen microbial protein synthesis from non-protein nitrogen, using phosphorus incorporation (PR). The nature of starch greatly influences urea utilization. Among the tropical tubers studied, yam Cayenesis and canna Edulis give lower urea utilization than cassava and yam Dumetorum. However, this can be improved by processing. The effects are greatest when the proportion of urea to processed cereal is ca. 4-5%. S-addition as sulfate improves urea utilization with both natural and purified diets. Part II. Results from the Jouy and Ghent laboratories were analyzed statistically, to check the accuracy of the 32P method for estimating microbial growth, using protein-free substrates. The linear relationship between PR and every other variable was studied. Two multivariate analyses, principal components and multiple regression, were applied. Net NH3 utilization was predicted using the equations for substrates with proteins likely to be degraded. This method appears more accurate than using the N/P ratio in microflora. Equations should only be used under the specific experiments described

  14. 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.

  15. Advances of small-molecule protein kinase inhibitor-based PET tracers with prospective application in pancreatic cancer%蛋白激酶小分子抑制剂PET显像研究进展及其在胰腺癌诊断中的应用前景

    Institute of Scientific and Technical Information of China (English)

    李詝; 朱朝晖; 李方

    2015-01-01

    Pancreatic cancer is one of the most common malignancies of digestive tract. The targeted therapeutic drugs and specific diagnostic probes for pancreatic cancer include antibodies, affinity ligands, polypeptides, and small-molecule protein kinase inhibitors. The research on small-molecule protein kinase inhibitors is a hot topic of both preclinical research and clinical application in recent years. The advances in this area were briefly reviewed in this article. Data indicated that H-89, a kind of isoquinoline sulfonamide small molecule, might be one of the best small-molecule protein kinase inhibitors to treat pancreatic cancer, and if labeled with positron emitter, it might become a potential PET tracer for pancreatic cancer.%胰腺癌为消化道较常见的恶性肿瘤。针对胰腺癌特异性诊断探针和靶向治疗的药物研究包括抗体、亲和体、多肽以及小分子化合物抑制剂,其中针对蛋白激酶的小分子抑制剂的研究备受关注。笔者综述了这一方向的PET示踪剂的研究进展,其中H-89作为异喹啉磺酰基类小分子化合物,可能是最好的胰腺癌蛋白激酶小分子抑制剂之一,用正电子核素标记后,可能成为较有潜力的胰腺癌PET示踪剂。

  16. Tracer studies on an aerated lagoon.

    Science.gov (United States)

    Broughton, Alistair; Shilton, Andy

    2012-01-01

    The city of Palmerston North, New Zealand, has two aerated lagoons as its secondary treatment facility. Interest about treatment efficiency led to an investigation into the hydraulics in the second lagoon to determine if further optimisation was viable. A tracer study using rhodamine WT was undertaken to ascertain the stimulus response output. Samples were also taken at 24 points within the lagoon to determine the tracer concentration profile throughout the lagoon. The mean residence time was determined to be 39.9 h compared with a theoretical residence time of 55.4 h. Peak concentration of the tracer at the outlet occurred at 0.44 of the mean residence time. The results of the tracer study pointed to 28% of volume being dead space. A subsequent sludge survey indicated that 26% of the design volume of the lagoon was filled with sludge. While the curved geometry of the lagoon did not appear to impact the hydraulics the fact that the first aerator is confined in a relatively smaller area will have locally boosted the mixing energy input in this inlet zone. From interpretation of the tracer response and the tracer distribution profiles it appears that the aerators are mixing the influent into the bulk flow effectively in the front end of the lagoon and that there was no evidence of any substantive short-circuiting path of concentrated tracer around to the outlet. The tracer distribution profiles gave direct insight as to how the tracer was being transported within the pond and should be used more often when conducting tracer studies. Comparison with the literature indicated that the lagoon's hydraulic efficiency was on par with a baffled pond system and it would be expected that addition of several baffles to the lagoon would provide minimal further improvement. PMID:22277219

  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. Analysis of colloid and tracer breakthrough curves

    Science.gov (United States)

    Grindrod, Peter; Edwards, Mark S.; Higgo, Jenny J. W.; Williams, Geoffrey M.

    1996-02-01

    We consider the dispersion and elution of colloids and dissolved nonsorbing tracers within saturated heterogeneous porous media. Since flow path geometry in natural systems is often ill-characterized macroscopic (mean) flow rates and dispersion tensors are utilized in order to account for the sub-model scale microscopic fluctuations in media structure (and the consequent hydrodynamic profile). Even for tracer migration and dispersal this issue is far from settled. Here we consider how colloid and tracer migration phenomena can be treated consistently. Theoretical calculations for model flow geometries yield two quantitative predictions for the transport of free (not yet captured) colloids with reference to a non-sorbing dissolved tracer within the same medium: the average migration velocity of the free colloids is higher than that of the tracer; and that the ratio of the equivalent hydrodynamic dispersion rates of colloids and tracer is dependent only upon properties of the colloids and the porous medium, it is independent of pathlengths and fluid flux, once length scales are large enough. The first of these is well known, since even in simple flow paths free colloids must stay more centre stream. The second, if validated suggests how solute and colloid dispersion may be dealt with consistently in macroscopic migration models. This is crucial since dispersion is usually ill-characterized and unaddressed by the experimental literature. In this paper we present evidence based upon an existing Drigg field injection test for the validity of these predictions. We show that starting from experimental data the fitted dispersion rates of both colloids and non-sorbing tracers increase with the measured elution rates (obeying slightly different rules for tracers and colloids); and that the ratio of colloid and nonsorbing tracer elution rates, and the ratio of colloid and nonsorbing tracer dispersion rates may be dependent upon properties of the colloids and the medium (not

  19. Curcumin-loaded silica-based mesoporous materials: Synthesis, characterization and cytotoxic properties against cancer cells.

    Science.gov (United States)

    Bollu, Vishnu Sravan; Barui, Ayan Kumar; Mondal, Sujan Kumar; Prashar, Sanjiv; Fajardo, Mariano; Briones, David; Rodríguez-Diéguez, Antonio; Patra, Chitta Ranjan; Gómez-Ruiz, Santiago

    2016-06-01

    Two different silica based (MSU-2 and MCM-41) curcumin loaded mesoporous materials V3 and V6 were synthesized and characterized by several physico-chemical techniques. Release kinetic study revealed the slow and sustained release of curcumin from those materials in blood simulated fluid (pH: 7.4). The materials V3 and V6 were found to be biocompatible in non-cancerous CHO cell line while exhibiting significant cytotoxicity in different cancer cells (human lung carcinoma cells: A549, human breast cancer cells: MCF-7, mouse melanoma cells: B16F10) compared to pristine curcumin indicating the efficacy of the mesoporous silica materials based drug delivery systems (DDSs). The generation of intracellular reactive oxygen species (ROS) and down regulation of anti-apoptotic protein leading to the induction of apoptosis were found to be the plausible mechanisms behind the anti-cancer activity of these DDSs. These results suggest that curcumin-loaded drug delivery system may be successfully employed as an alternative treatment strategy for cancer therapeutics through a nanomedicine approach in near future. PMID:27040234

  20. 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. PMID:26176269

  1. 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).

  2. 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.

  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. Novel Improved Synthesis of HSP70 Inhibitor, Pifithrin-μ. In Vitro Synergy Quantification of Pifithrin-μ Combined with Pt Drugs in Prostate and Colorectal Cancer Cells.

    Science.gov (United States)

    McKeon, Aoife M; Egan, Alan; Chandanshive, Jay; McMahon, Helena; Griffith, Darren M

    2016-01-01

    We describe a novel improved approach to the synthesis of the important and well-known heat shock protein 70 inhibitor (HSP70), pifithrin-μ, with corresponding and previously unreported characterisation. The first example of a combination study comprising HSP70 inhibitor pifithrin-μ and cisplatin or oxaliplatin is reported. We have determined, using the Chou-Talalay method, (i) moderate synergistic and synergistic effects in co-treating PC-3 prostate cancer cells with pifithrin-μ and cisplatin and (ii) significant synergistic effects including strong synergism in cotreating HT29 colorectal cancer cells with oxaliplatin and pifithrin-μ. PMID:27455212

  6. Novel Improved Synthesis of HSP70 Inhibitor, Pifithrin-μ. In Vitro Synergy Quantification of Pifithrin-μ Combined with Pt Drugs in Prostate and Colorectal Cancer Cells

    Directory of Open Access Journals (Sweden)

    Aoife M. McKeon

    2016-07-01

    Full Text Available We describe a novel improved approach to the synthesis of the important and well-known heat shock protein 70 inhibitor (HSP70, pifithrin-μ, with corresponding and previously unreported characterisation. The first example of a combination study comprising HSP70 inhibitor pifithrin-μ and cisplatin or oxaliplatin is reported. We have determined, using the Chou-Talalay method, (i moderate synergistic and synergistic effects in co-treating PC-3 prostate cancer cells with pifithrin-μ and cisplatin and (ii significant synergistic effects including strong synergism in cotreating HT29 colorectal cancer cells with oxaliplatin and pifithrin-μ.

  7. 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.

  8. 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.

  9. The design and synthesis of novel N-heterocyclic compounds, and their evaluation of anti-cancer and anti-viral activity

    OpenAIRE

    More, Vijaykumar

    2014-01-01

    2010 - 2011 The thesis entitled “The design and synthesis of novel N-heterocyclic compounds, and their evaluation of anti-cancer and anti-viral activity" is divided into three chapters. The title of the thesis clearly reflects the importance of nitrogen heterocycles compounds: in fact they are extremely pivotal structural motifs responsible for eliciting various biological activities in natural products and synthetic medicines. This has attracted the medicinal chemists towards the synth...

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

    International Nuclear Information System (INIS)

    Highlights: ► Metformin inhibits cancer cell growth but the mechanism(s) are not understood. ► We show that the potency of metformin is sharply dependent on glucose in the medium. ► AMPK activation was enhanced in cancer cells incubated in physiological glucose. ► Reciprocally, metformin potently inhibited mTORC1, DNA synthesis and proliferation. ► 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 Ser79 and Raptor at Ser792, 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 α1 and α2 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.

  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. 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. 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.

  14. Design, Synthesis, and Characterization of Folate-Targeted Platinum-Loaded Theranostic Nanoemulsions for Therapy and Imaging of Ovarian Cancer.

    Science.gov (United States)

    Patel, Niravkumar R; Piroyan, Aleksandr; Nack, Abbegial H; Galati, Corin A; McHugh, Mackenzi; Orosz, Samantha; Keeler, Amanda W; O'Neal, Sara; Zamboni, William C; Davis, Barbara; Coleman, Timothy P

    2016-06-01

    Platinum (Pt) based chemotherapy is widely used to treat many types of cancer. Pt therapy faces challenges such as dose limiting toxicities, cumulative side effects, and multidrug resistance. Nanoemulsions (NEs) have tremendous potential in overcoming these challenges as they can be designed to improve circulation time, limit non-disease tissue uptake, and enhance tumor uptake by surface modification. We designed novel synthesis of three difattyacid platins, dimyrisplatin, dipalmiplatin, and distearyplatin, suitable for encapsulation in the oil core of an NE. The dimyrisplatin, dipalmiplatin, and distearyplatin were synthesized, characterized, and loaded into the oil core of our NEs, NMI-350, NMI-351, and NMI-352 respectively. Sequestration of the difattyacid platins was accomplished through high energy microfluidization. To target the NE, FA-PEG3400-DSPE was incorporated into the surface during microfluidization. The FA-NEs selectively bind the folate receptor α (FR-α) and utilize receptor mediated endocytosis to deliver Pt past cell surface resistance mechanisms. FR-α is overexpressed in a number of oncological conditions including ovarian cancer. The difattyacid platins, lipidated Gd-DTPA, and lipidated folate were characterized by nuclear magnetic resonance (NMR), mass spectrometry (MS), and elemental analysis. NEs were synthesized using high shear microfluidization process and characterized for size, zeta-potential, and loading efficiency. In vitro cytotoxicity was determined using KB-WT (Pt-sensitive) and KBCR-1000 (Pt-resistant) cancer cells and measured by MTT assay. Pharmacokinetic profiles were studied in CD-1 mice. NEs loaded with difattyacid platins are highly stable and had size distribution in the range of ∼120 to 150 nm with low PDI. Cytotoxicity data indicates the longer the fatty acid chains, the less potent the NEs. The inclusion of C6-ceramide, an apoptosis enhancer, and surface functionalization with folate molecules significantly increased

  15. 15N tracer kinetic studies on the validity of various 15N tracer substances for determining whole-body protein parameters in very small preterm infants

    International Nuclear Information System (INIS)

    Reliable 15N tracer substances for tracer kinetic determination of whole-body protein parameters in very small preterm infants are still a matter of intensive research, especially after some doubts have been raised about the validity of [15N]glycine, a commonly used 15N tracer. Protein turnover, synthesis, breakdown, and further protein metabolism data were determined by a paired comparison in four preterm infants. Their post-conceptual age was 32.2 +/- 0.8 weeks, and their body weight was 1670 +/- 181 g. Tracer substances applied in this study were a [15N]amino acid mixture (Ia) and [15N]glycine (Ib). In a second group of three infants with a post conceptual age of 15N-labeled 32.0 +/- 1.0 weeks and a body weight of 1,907 +/- 137 g, yeast protein hydrolysate (II) was used as a tracer substance. A three-pool model was employed for the analysis of the data. This model takes into account renal and fecal 15N losses after a single 15N pulse. Protein turnovers were as follows: 11.9 +/- 3.1 g kg-1 d-1 (Ia), 16.2 +/- 2.5 g kg-1 d-1 (Ib), and 10.8 +/- 3.0 g kg-1 d-1 (II). We were able to demonstrate an overestimation of the protein turnover when Ib was used. There was an expected correspondence in the results obtained from Ia and II. The 15N-labeled yeast protein hydrolysate is a relatively cheap tracer that allows reliable determination of whole-body protein parameters in very small preterm infants

  16. 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.

  17. 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

  18. 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

  19. Facile synthesis, pharmacokinetic and systemic clearance evaluation, and positron emission tomography cancer imaging of 64Cu-Au alloy nanoclusters

    Science.gov (United States)

    Zhao, Yongfeng; Sultan, Deborah; Detering, Lisa; Luehmann, Hannah; Liu, Yongjian

    2014-10-01

    Gold nanoparticles have been widely used for oncological applications including diagnosis and therapy. However, the non-specific mononuclear phagocyte system accumulation and potential long-term toxicity have significantly limited clinical translation. One strategy to overcome these shortcomings is to reduce the size of gold nanoparticles to allow renal clearance. Herein, we report the preparation of 64Cu alloyed gold nanoclusters (64CuAuNCs) for in vivo evaluation of pharmacokinetics, systemic clearance, and positron emission tomography (PET) imaging in a mouse prostate cancer model. The facile synthesis in acqueous solution allowed precisely controlled 64Cu incorporation for high radiolabeling specific activity and stability for sensitive and accurate detection. Through surface pegylation with 350 Da polyethylene glycol (PEG), the 64CuAuNCs-PEG350 afforded optimal biodistribution and significant renal and hepatobiliary excretion. PET imaging showed low non-specific tumor uptake, indicating its potential for active targeting of clinically relevant biomarkers in tumor and metastatic organs.Gold nanoparticles have been widely used for oncological applications including diagnosis and therapy. However, the non-specific mononuclear phagocyte system accumulation and potential long-term toxicity have significantly limited clinical translation. One strategy to overcome these shortcomings is to reduce the size of gold nanoparticles to allow renal clearance. Herein, we report the preparation of 64Cu alloyed gold nanoclusters (64CuAuNCs) for in vivo evaluation of pharmacokinetics, systemic clearance, and positron emission tomography (PET) imaging in a mouse prostate cancer model. The facile synthesis in acqueous solution allowed precisely controlled 64Cu incorporation for high radiolabeling specific activity and stability for sensitive and accurate detection. Through surface pegylation with 350 Da polyethylene glycol (PEG), the 64CuAuNCs-PEG350 afforded optimal

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

    International Nuclear Information System (INIS)

    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. 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. 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 heparanase 2, which displays anti-metastatic features

  1. Synthesis and Investigation of Novel Spiro-isoxazolines as Anti-Cancer Agents

    Science.gov (United States)

    Das, Prasanta; Omollo, Ann O.; Sitole, Lungile J.; McClendon, Eric; Valente, Edward J.; Raucher, Drazen; Walker, Leslie R.; Hamme, Ashton T.

    2015-01-01

    A series of structurally diverse 4-bromo spiro-isoxazolines possessing a variety of aromatic and aliphatic substituents at the 3 position, were synthesized through a 1,3-dipolar cycloaddition followed by intramolecular cyclization of a pendant hydroxyl or carboxylic acid group. The biochemical antiproliferative activity was evaluated in vitro by using two breast cancer cell lines (MCF-7 and MDA-MB-231) and two prostate cancer cell lines (PC-3 and DU-145) using the MTT viability assay, and the IC50 values were obtained. Spiro-isoxazoline derivatives bearing a p-chloro or an o-dichloro aromatic substituent at the 3-position of the isoxazoline showed considerable antitumor activities in all four cell lines with IC50 value ranging from 43μM to 56μM. PMID:25821250

  2. 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

  3. 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

  4. Facile synthesis of superparamagnetic Fe3O4@Au nanoparticles for photothermal destruction of cancer cells.

    Science.gov (United States)

    Ren, Jinfeng; Shen, Shun; Pang, Zhiqing; Lu, Xiaohui; Deng, Chunhui; Jiang, Xinguo

    2011-11-14

    Superparamagnetic Fe(3)O(4) nanoparticles with positive surface ξ-potential were synthesized via a solvothermal route. After Fe(3)O(4) was mixed with HAuCl(4) and NaBH(4), the reduced Au nanoparticles could be directly adsorbed onto the surface of Fe(3)O(4) nanoparticles. The as-synthesized nanocomposites were successfully applied to photothermal destruction of cancer cells. PMID:21952492

  5. 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.

  6. Synthesis and characterization of nano structures of Silica SBA-16 containing Gadolinium-159 as potential nanoparticulated system for cancer therapy

    International Nuclear Information System (INIS)

    Cancer is a leading cause of death worldwide, and malignant neoplasms of the lung, stomach, liver, colon and breast in greater numbers. And recently observed in the literature a large number of reviews where new materials, especially nanoparticle, has been studied as drug carriers and radioisotopes applied to cancer treatment. How mesoporous materials based on silica, thanks to its huge surface area and biocompatibility, have been studied intensively providing broad applications in various areas, the use of nanostructured silica SBA-16 might be a carrier specific radioisotope accumulate in the cells malignant. Thus the aim of this study is to develop in vitro studies using SBA-16 can selectively concentrate in malignant cells therapeutic amounts of the radioisotope Gadolinium-159 escorting them to death. This work was performed orderly synthesis of mesoporous silica, SBA-16 and incorporating the complex Gd-DTPA-BMA, as well as chemical and structural characterization. The techniques used to analyze the occurrence of the incorporation of the gadolinium complex in the silica matrix were elemental analysis (CHN), atomic emission spectroscopy (ICP-AES), infrared spectroscopy (FTIR), nitrogen adsorption (BET), small-angle X-ray scattering (SAXS) and thermogravimetric analysis (TG). To analyze the morphology of pure silica used the scanning electron microscopy (SEM) and transmission electron microscopy (TEM). By photon correlation spectroscopy (PCS) it was possible to obtain a measure of mean particle size, the polydispersity index (PDI) of the silica SBA-16, and the zeta potential by laser Doppler anemometry (LDA). The results of incorporation analyzed by ICP-AES indicated that the material SBA-16 had a higher rate of incorporation of gadolinium (93%). The release kinetics in simulated body fluid, showed considerable stability and low release (1%). The mesoporous silica SBA-16 showed cell viability in direct contact with cell culture. Samples with gadolinium

  7. 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

  8. 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.

  9. 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.

  10. A novel ibuprofen derivative with anti-lung cancer properties: synthesis, formulation, pharmacokinetic and efficacy studies.

    Science.gov (United States)

    Cheng, Ka-Wing; Nie, Ting; Ouyang, Nengtai; Alston, Ninche; Wong, Chi C; Mattheolabakis, George; Papayannis, Ioannis; Huang, Liqun; Rigas, Basil

    2014-12-30

    Phospho-non-steroidal anti-inflammatory drugs (phospho-NSAIDs) are a novel class of NSAID derivatives with potent antitumor activity. However, phospho-NSAIDs have limited stability in vivo due to their rapid hydrolysis by carboxylesterases at their carboxylic ester link. Here, we synthesized phospho-ibuprofen amide (PIA), a metabolically stable analog of phospho-ibuprofen, formulated it in nanocarriers, and evaluated its pharmacokinetics and anticancer efficacy in pre-clinical models of human lung cancer. PIA was 10-fold more potent than ibuprofen in suppressing the growth of human non-small-cell lung cancer (NSCLC) cell lines, an effect mediated by favorably altering cytokinetics and inducing oxidative stress. Pharmacokinetic studies in rats revealed that liposome-encapsulated PIA exhibited remarkable resistance to hydrolysis by carboxylesterases, remaining largely intact in the systemic circulation, and demonstrated selective distribution to the lungs. The antitumor activity of liposomal PIA was evaluated in a metastatic model of human NSCLC in mice. Liposomal PIA strongly inhibited lung tumorigenesis (>95%) and was significantly (pibuprofen. We observed a significant induction of urinary 8-iso-prostaglandin F2αin vivo, which indicates that ROS stress probably plays an important role in mediating the antitumor efficacy of PIA. Our findings suggest that liposomal PIA is a potent agent in the treatment of lung cancer and merits further evaluation.

  11. Radioactive and kinematic tracers of feedback from massive stars

    Directory of Open Access Journals (Sweden)

    Voss R.

    2012-02-01

    Full Text Available The mixing of ejecta from young stars into the interstellar medium is an important process in the interplay between star formation and galaxy evolution. A unique window into these processes is provided by the radioactive isotopes 26Al, traced by its γ-ray decay lines at 1.8 MeV. With a mean lifetime of ∼ 1 Myr it is a long-term tracer of nucleosynthesis for massive stars. Our population synthesis code models the ejection of 26Al, together with the 60Fe, the kinetic energy and UV radiation for a population of massive stars. We have applied the code to study the nearby Orion region and the more massive Carina region and found good agreement with observational constraints.

  12. Delta-Opioid Receptor (δOR) Targeted Near-Infrared Fluorescent Agent for Imaging of Lung Cancer: Synthesis and Evaluation In Vitro and In Vivo.

    Science.gov (United States)

    Cohen, Allison S; Patek, Renata; Enkemann, Steven A; Johnson, Joseph O; Chen, Tingan; Toloza, Eric; Vagner, Josef; Morse, David L

    2016-02-17

    In the United States, lung cancer is the leading cause of cancer death and ranks second in the number of new cases annually among all types of cancers. Better methods or tools for diagnosing and treating this disease are needed to improve patient outcomes. The delta-opioid receptor (δOR) is reported to be overexpressed in lung cancers and not expressed in normal lung. Thus, we decided to develop a lung cancer-specific imaging agent targeting this receptor. We have previously developed a δOR-targeted fluorescent imaging agent based on a synthetic peptide antagonist (Dmt-Tic) conjugated to a Cy5 fluorescent dye. In this work, we describe the synthesis of Dmt-Tic conjugated to a longer wavelength near-infrared fluorescent (NIRF) dye, Li-cor IR800CW. Binding affinity of Dmt-Tic-IR800 for the δOR was studied using lanthanide time-resolved fluorescence (LTRF) competitive binding assays in cells engineered to overexpress the δOR. In addition, we identified lung cancer cell lines with high and low endogenous expression of the δOR. We confirmed protein expression in these cell lines using confocal fluorescence microscopy imaging and used this technique to estimate the cell-surface receptor number in the endogenously expressing lung cancer cell lines. The selectivity of Dmt-Tic-IR800 for imaging of the δOR in vivo was shown using both engineered cell lines and endogenously expressing lung cancer cells in subcutaneous xenograft models in mice. In conclusion, the δOR-specific fluorescent probe developed in this study displays excellent potential for imaging of lung cancer. PMID:26488422

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

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    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.

  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. The quality of research synthesis in surgery: the case of laparoscopic surgery for colorectal cancer

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    Martel Guillaume

    2012-02-01

    Full Text Available Abstract Background Several systematic reviews and meta-analyses populate the literature on the effectiveness of laparoscopic surgery for colorectal cancer. The utility of this body of work is unclear. The objective of this study was to synthesize all such systematic reviews in terms of clinical effectiveness, to appraise their quality, and to determine whether areas of duplication exist across reviews. Methods Systematic reviews comparing laparoscopic and open surgery for colorectal cancer were identified using a comprehensive search protocol (1991 to 2008. The primary outcome was overall survival. The methodological quality of reviews was appraised using the Assessment of Multiple Systematic Reviews (AMSTAR instrument. Abstraction and quality appraisal was carried out by two independent reviewers. Reviews were synthesized, and outcomes were compared qualitatively. A citation analysis was carried out using simple matrices to assess the comprehensiveness of each review. Results In total, 27 reviews were included; 13 reviews included only randomized controlled trials. Rectal cancer was addressed exclusively by four reviews. There was significant overlap between review purposes, populations and, outcomes. The mean AMSTAR score (out of 11 was 5.8 (95% CI: 4.6 to 7.0. Overall survival was evaluated by ten reviews, none of which found a significant difference. Three reviews provided a selective meta-analysis of time-to-event data. Previously published systematic reviews were poorly and highly selectively referenced (mean citation ratio 0.16, 95% CI: 0.093 to 0.22. Previously published trials were not comprehensively identified and cited (mean citation ratio 0.56, 95% CI: 0.46 to 0.65. Conclusions Numerous overlapping systematic reviews of laparoscopic and open surgery for colorectal cancer exist in the literature. Despite variable methods and quality, survival outcomes are congruent across reviews. A duplication of research efforts appears to exist

  16. 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

  17. Synthesis and biological evaluation of retinoid-chalcones as inhibitors of colon cancer cell growth

    OpenAIRE

    Mizuno, Cassia S.; Paul, Shiby; Suh, Nanjoo; Rimando, Agnes M.

    2010-01-01

    Based on the observed anticancer activity of chalcones and retinoids, a novel class of retinoid-chalcone hybrids was 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 cell line HT-29. Retinoid like moiety was introduced through Friedel-Crafts alkylation of toluene. Among the synthesized compounds, the cyano derivative (E)-3-(3-oxo-3-(3,5,5,8,8-pentamethyl-5,6,7,8-t...

  18. Synthesis and Evaluation of Nanogold Bioconjugated with Trastuzumab as a Drug for Human Breast Cancer Cell Line

    International Nuclear Information System (INIS)

    Breast cancer had been registered as the first order of cancer's leading cause of carcinoma death among Iraqi women. There are different trials to use bionanotechnology in medicine especially in the treatment of breast cancer. This work aimed to use different types of gold nanoparticles (GNPs) in application and evaluation of breast cancer cell through the following parts:- Part I: Synthesis three types of GNPs included: 1- Gold nanospheres (GN spheres) by modification of the chemical method and using different reducing agent (sodium borohydride then capping with glutathione (GSH), the other method by using GSH and the last using new reducing agent (2-Oxoglutaric acid). To the our present knowledge, this is the first report about using 2-Oxoglutaric acidas reducing agent in the synthesis of GN spheres. 2- Gold nanorods (GNRs)by using seed - mediated growth method capped with cetyltrimethyl ammonium bromide (CTAB). 3- Gold nano shells (GNSs) by using silica nanoparticles as core and seeded with gold as shell (silica-gold core shells). All the prepared types GNPs were characterized by using eight different techniques including: Atomic force microscopy (AFM),Transmission Electron Microscope (TEM), Field Emission Scanning Electron Microscopy (FESEM), UV-Vis spectroscopy, Dynamic light scattering (DLS), Fourier Transform Infrared (FTIR), Inductively Coupled Plasma- Optical Emission Spectrometry (ICP-OES), and zeta nanosizer. The measurements were done in Tarbiat Modares University (Faculty of Medicine and Faculty of Biological sciences) and Tehran University in Islamic Republic of Iran, except the techniques of ICP-OES it was done in Al-Sulaimani Universityandthat of AFM was accomplished in the Ministry of Science and Technology in Iraq . Part II: This part includes two steps: 1- Biofunctionalization i.e., modification of the surfaces of the three types of prepared GNPs by coating with thiol-poly ethylene glycol -carboxy (SH-PEG-COOH) then activation of the

  19. 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.

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

    Science.gov (United States)

    Bingul, Murat; Tan, Owen; Gardner, Christopher R; Sutton, Selina K; Arndt, Greg M; Marshall, Glenn M; Cheung, Belamy B; Kumar, Naresh; Black, David StC

    2016-01-01

    Identification of the novel (E)-N'-((2-chloro-7-methoxyquinolin-3-yl)methylene)-3-(phenylthio)propanehydrazide 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 p27(kip1) cell cycle regulating protein. PMID:27428941

  1. Synthesis and evaluation of polymeric gold glyco-conjugates as anti-cancer agents.

    Science.gov (United States)

    Ahmed, Marya; Mamba, Saul; Yang, Xiao-Hong; Darkwa, James; Kumar, Piyush; Narain, Ravin

    2013-06-19

    The antitumor activity of organo-gold compounds is a focus of research from the past two decades. A variety of gold stabilizing ligands such as vitamins and xanthanes have been prepared and explored for their 'chelating effect' as well as for their antitumor activity. Dithiocarbamates (DTC) compounds and their metallic conjugates have been well explored for their antiproliferative activities. In this study, glycopolymer based DTC-conjugates are prepared by reversible addition-fragmentation chain transfer polymerization (RAFT) and subsequently modified with gold(I) phosphine. These polymer-DTC derivatives and their gold compounds are tested for their in vitro toxicity in both normal and cancer cell lines. The Au(I) phosphine conjugated cationic glycopolymers of 10 kDa and 30 kDa are evaluated for their cytotoxicity profiles using MTT assay. Au(I) compounds are well-known for their mitochondrial toxicity, hence hypoxic cell lines bearing unusually enlarged mitochondria are subjected to these anticancer compounds. It is concluded that these polymeric DTC derivatives and their gold conjugates indeed show higher accumulation as well as cytotoxicity to cancer cells under hypoxic conditions in comparison to the normoxic ones. Hypoxic MCF-7 cells showed significant sensitivity toward the low molecular weight (10 kDa) glycopolymer-Au(I) complexes. PMID:23631753

  2. 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.

  3. Synthesis, Characterization and Biological Evaluation of Succinate Prodrugs of Curcuminoids for Colon Cancer Treatment

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    Pornchai Rojsitthisak

    2011-02-01

    Full Text Available A novel series of succinyl derivatives of three curcuminoids were synthesized as potential prodrugs. Symmetrical (curcumin and bisdesmethoxycurcumin and unsymmetrical (desmethoxycurcumin curcuminoids were prepared through aldol condensation of 2,4-pentanedione with different benzaldehydes. Esterification of these compounds with a methyl or ethyl ester of succinyl chloride gave the corresponding succinate prodrugs in excellent yields. Anticolon cancer activity of the compounds was evaluated using Caco-2 cells. The succinate prodrugs had IC50 values in the 1.8–9.6 ��M range, compared to IC50 values of 3.3–4.9 μM for the parent compounds. Curcumin diethyl disuccinate exhibited the highest potency and was chosen for stability studies. Hydrolysis of this compound in phosphate buffer at pH 7.4 and in human plasma followed pseudo first-order kinetics. In phosphate buffer, the kobs and t1/2 for hydrolysis indicated that the compound was much more stable than curcumin. In human plasma, this compound was able to release curcumin, therefore our results suggest that succinate prodrugs of curcuminoids are stable in phosphate buffer, release the parent curcumin derivatives readily in human plasma, and show anti-colon cancer activity.

  4. Mitomycin-C+fluoropyrimidines in heavily pretreated metastatic colorectal cancer: a systematic review and evidence synthesis.

    Science.gov (United States)

    Petrelli, Fausto; Ghidini, Antonio; Inno, Alessandro; Barni, Sandro

    2016-07-01

    Mitomycin-C (MMC) combined with fluoropyrimidines has historically been used for pretreated patients with some activity in this setting, in particular, as third-line chemotherapy (CT) or beyond. We have evaluated the efficacy and safety of MMC-based therapy as a further line of CT in advanced colorectal cancer. Prospective or retrospective studies of MMC-based CT were included in the pooled analysis. PubMed, EMBASE, SCOPUS, Web of Science, the Cochrane Library database and CINAHL were searched systematically. The outcomes were progression-free survival, overall survival, overall response rate and grades 3-4 drug-related adverse events. Seventeen trials involving 681 patients were included in the analysis. Overall, the pooled average weighted progression-free survival and overall survival were 2.84 [95% confidence interval (CI) 2.5-3.1] and 7.47 (95% CI 6-8.9) months, respectively. The corresponding pooled overall response rate was 7.2% (95% CI 5.2-9.9%) and the pooled disease control rate was 38.7% (95% CI 31.7-46.3%). The G3-4 neutropenia and anaemia were the most frequent haematological toxicities (range 0-20%). Nonhaematological G3-4 toxicities were compatible with the associated agent. MMC with fluoropyrimidines represents a viable and active combination for pretreated metastatic colorectal cancer patients. It is thus an option when other agents have failed, or are unavailable or not indicated. PMID:27186954

  5. 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.

  6. Advantages of a dual-tracer model over reference tissue models for binding potential measurement in tumors

    International Nuclear Information System (INIS)

    The quantification of tumor molecular expression in vivo could have a significant impact for informing and monitoring emerging targeted therapies in oncology. Molecular imaging of targeted tracers can be used to quantify receptor expression in the form of a binding potential (BP) if the arterial input curve or a surrogate of it is also measured. However, the assumptions of the most common approaches (reference tissue models) may not be valid for use in tumors. In this study, the validity of reference tissue models is investigated for use in tumors experimentally and in simulations. Three different tumor lines were grown subcutaneously in athymic mice and the mice were injected with a mixture of an epidermal growth factor receptor-targeted fluorescent tracer and an untargeted fluorescent tracer. A one-compartment plasma input model demonstrated that the transport kinetics of both tracers was significantly different between tumors and all potential reference tissues, and using the reference tissue model resulted in a theoretical underestimation in BP of 50% ± 37%. On the other hand, the targeted and untargeted tracers demonstrated similar transport kinetics, allowing a dual-tracer approach to be employed to accurately estimate BP (with a theoretical error of 0.23% ± 9.07%). These findings highlight the potential for using a dual-tracer approach to quantify receptor expression in tumors with abnormal hemodynamics, possibly to inform the choice or progress of molecular cancer therapies. (paper)

  7. Proceedings of Tracer 3. International Conference on Tracers and Tracing Methods

    International Nuclear Information System (INIS)

    Tracer 3 conference is a continuation of former Tracer 1 (1998) and Tracer 2 (2001) conferences organized by CNRS - Nancy France. The objective of this 3rd conference is presentation of different aspects of tracer method applications and development of tracer methodology.The new field of activity presented at the Conference was application of stable isotopes as natural tracers for investigations of environmental processes. The conference gave the possibility for scientific information exchange between specialists from different fields of activity such as chemical engineering, chemistry, bioengineering, environmental engineering, hydrology, civil engineering, metallurgy, etc. The presentations were divided into groups covering the principal items of Conference. Section A. Fundamental development - RTD and tracer methodology, - RTD methodology and Computational Fluid Dynamics (CFD), - New tracers and detectors. Section B. Industrial applications - Environment, - Geology, hydrogeology and oil field applications, - Civil engineering, mineral engineering and metallurgy applications, - Food engineering and bioengineering, - Material engineering, - Chemical engineering. During the Conference INIS promotion materials were exposed by INIS liaison officer for Poland

  8. Cancer

    Science.gov (United States)

    ... Blood tests (which look for chemicals such as tumor markers) Bone marrow biopsy (for lymphoma or leukemia) Chest ... the case with skin cancers , as well as cancers of the lung, breast, and colon. If the tumor has spread ...

  9. 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 ...

  10. 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

  11. 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

  12. 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

  13. Exploring Hydrofluorocarbons as Groundwater Age Tracers (Invited)

    Science.gov (United States)

    Haase, K. B.; Busenberg, E.; Plummer, L. N.; Casile, G.; Sanford, W. E.

    2013-12-01

    Groundwater dating tracers are an essential tool for analyzing hydrologic conditions in groundwater systems. Commonly used tracers for dating post-1940's groundwater include sulfur hexafluoride (SF6), chlorofluorocarbons (CFCs), 3H-3He, and other isotopic tracers (85Kr, δ2H and δ18O isotopes, etc.). Each tracer carries a corresponding set of advantages and limitations imposed by field, analytical, and interpretive methods. Increasing the number available tracers is appealing, particularly if they possess inert chemical properties and unique temporal emission histories from other tracers. Atmospherically derived halogenated trace gases continue to hold untapped potential for new tracers, as they are generally inert and their emission histories are well documented. SF5CF3, and CFC-13 were previously shown to have application as dating tracers, though their low mixing ratios and low solubility require large amounts of water to be degassed for their quantification. Two related groups of compounds, hydrochlorofluorocarbons (HCFCs) and hydrofluorocarbons (HFCs) are hypothesized to be potential age tracers, having similar mixing ratios to the CFCs and relatively high solubility. However, these compounds yield gas chromatography electron capture detector (GC-ECD) responses that are 10-2 -10-5 less than CFC-12, making purge and trap or field stripping GC-ECD approaches impractical. Therefore, in order to use dissolved HCFCs and HFCs as age tracers, different approaches are needed. To solve this problem, we developed an analytical method that uses an atomic emission detector (GC-AED) in place of an ECD to detect fluorinated compounds. In contrast to the ECD, the AED is a universally sensitive, highly linear, elementally specific detector. The new GC-AED system is being used to measure chlorodifluoromethane (HCFC-22), 1,1,1,2-tetrafluoroethane (HFC-134a), and other fluorinated compounds in one liter water samples to study their potential as age dating tracers. HCFC-22 is a

  14. 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.

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

    Science.gov (United States)

    González, Maykel; Merino, Ulises; Vargas, Susana; Quintanilla, Francisco; Rodríguez, Rogelio

    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) [Cl2-Pt-(NH3)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. PMID:26838911

  16. 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).

  17. Synthesis and characterization of rare earth molybdates nanoparticles for detection of specific prostatic cancer (PSA)

    International Nuclear Information System (INIS)

    The interest in using rare earths to investigate the properties and functions of biochemical systems as well as to determinate biological substances has increased in several fields, including biomarkers in immunology (fluoro immunoassays). Nowadays the use of lanthanides in the diagnosis of various diseases have become more important through the development of commercial diagnostic kits. As main feature, these rare earths can show a long lifetime, photo stability and emission bands of atomic like behavior and well defined, in the visible region, demonstrating unique advantages when compared to other luminescent species. The present work had as its goal to synthesize rare earth molybdates by the co-precipitation method as well as to characterize these materials by X-ray diffraction, near infrared spectroscopy, thermogravimetric analysis, scanning electronic microscopy, transmission electronic microscopy and luminescent studies. In this work, three different studied were developed: the influence of the vortex speed variation during co-precipitation in the structure of the final product, morphology and luminescence properties; the influence of the annealing temperature also in the structure, morphology and luminescence properties; and the influence of concentration of the doping in the luminescence properties. Another important step of this work was the functionalization of nanoparticles using an organosilane (APTES) to coat and establish points for binding the particles to biological species. It was proved that this process was very efficient by the characterization results and the silica incorporation was well succeeded. Specific prostatic cancer (PSA) was then linked to the functionalized nanoparticles to diagnostic prostatic cancer by fluoroimmunoassay and levels for detection were established. (author)

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

    Energy Technology Data Exchange (ETDEWEB)

    Hopperton, Kathryn E., E-mail: kathryn.hopperton@mail.utoronto.ca [Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, Canada M5S 3E2 (Canada); Duncan, Robin E., E-mail: robin.duncan@uwaterloo.ca [Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, Canada M5S 3E2 (Canada); Bazinet, Richard P., E-mail: richard.bazinet@utoronto.ca [Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, Canada M5S 3E2 (Canada); Archer, Michael C., E-mail: m.archer@utoronto.ca [Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, Canada M5S 3E2 (Canada); Department of Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, ON, Canada M5S 3E2 (Canada)

    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 {sup 14}C-labeled acetate to those supplied exogenously as {sup 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. - Highlights: • Fatty acid synthase (FASN) is over-expressed in cancer but its function is unknown. • We compare

  19. 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。

  20. 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.

  1. Particle and tracer diffusion in complex liquids

    Science.gov (United States)

    Koynov, Kaloian; Butt, Hans-Jürgen

    2013-02-01

    The diffusion of fluorescent tracers can be studied using fluorescence correlation spectroscopy (FCS). This powerful method offers the possibility to monitor very small tracers at low concentrations, down to single molecules. Furthermore it possesses a sub-femtoliter detection volume that can be precisely positioned in a heterogeneous environment to probe the local dynamics. Despite its great potential and high versatility in addressing the diffusion and transport properties in complex systems, FCS has been predominantly applied in molecular and cell biology. Here we present some applications that are more relevant for material and soft matter science. First, we study the diffusion of single tracers with molecular sizes in undiluted polymer systems. Next, the diffusion of small molecules and semiconductor nanoparticles (quantum dots) in silica inverse opals is studied and correlated to the size and morphology of the inverse opals. Finally, we show how FCS can be used to measure the diffusion coefficient of nanoparticles at water-oil interfaces.

  2. 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.

  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. Spiro[pyrrolidine-3, 3´-oxindole] as potent anti-breast cancer compounds: Their design, synthesis, biological evaluation and cellular target identification.

    Science.gov (United States)

    Hati, Santanu; Tripathy, Sayantan; Dutta, Pratip Kumar; Agarwal, Rahul; Srinivasan, Ramprasad; Singh, Ashutosh; Singh, Shailja; Sen, Subhabrata

    2016-01-01

    The spiro[pyrrolidine-3, 3´-oxindole] moiety is present as a core in number of alkaloids with substantial biological activities. Here in we report design and synthesis of a library of compounds bearing spiro[pyrrolidine-3, 3´-oxindole] motifs that demonstrated exceptional inhibitory activity against the proliferation of MCF-7 breast cancer cells. The synthesis involved a one pot Pictet Spengler-Oxidative ring contraction of tryptamine to the desired scaffolds and occurred in 1:1 THF and water with catalytic trifluoroacetic acid and stoichiometric N-bromosuccinimide as an oxidant. Phenotypic profiling indicated that these molecules induce apoptotic cell death in MCF-7 cells. Target deconvolution with most potent compound 5l from the library, using chemical proteomics indicated histone deacetylase 2 (HDAC2) and prohibitin 2 as the potential cellular binding partners. Molecular docking of 5l with HDAC2 provided insights pertinent to putative binding interactions. PMID:27573798

  5. Use of radioactive tracers in dynamic sedimentology

    International Nuclear Information System (INIS)

    In the first part, developments in the use of radioactive tracers in sedimentology are recalled together with the corresponding fields of application and the identities of the main users. The state-of-the-art in France is also discussed; The main characteristics of the method are then described and compared with those of more classical methods. The results that can be obtained with tracer methods are then outlined. The criteria employed to establish the granulometry characteristics of the tracer, the particular radioisotope to be used, and the masses and activities involved, are treated. A list is then given of the main isotopes available in France and their characteristics. The various different labelling techniques employed are studied together with their respective advantages and disadvantages. The special case of pelitic sediments is mentioned. The use of reduced model isotope generators, double labelling and applications to studies of the mud plug in the Gironde Estuary are also discussed. The methods and materials used for injecting and detecting tracers are described, emphasis being given to the economic factors associated with the use of radioactive tracers in sedimentology. The second part of the report contains two chapters: - studies of transport by driftage: presentation and analysis of results and the application of the Count Rate Balance method to obtain quantitative information on transport; - studies of in-suspension transport of fine sediments in the sea: the procedures adopted from the moment when the tracer is introduced up to the time when the results are analyzed and interpreted, enables the trajectories and mean velocities of the transported sediments to be determined together with their degree of dilution and their settling speeds and rates; it is also possible to investigate the evolution and horizontal dispersion of the sediments in this way. Results from recent experiments are presented in both parts of the report

  6. 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.

  7. 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.

  8. 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.

  9. Synthesis of novel flavone derivatives possessing substituted benzamides and their biological evaluation against human cancer cells.

    Science.gov (United States)

    Yun, Bo Hee; Lee, Young Hun; Park, Kyung Tae; Jung, Su Jin; Lee, Yong Sup

    2016-09-01

    Baicalein is a well-known flavone derivative that possesses diverse biological properties, such as anticancer, antioxidant and anti-inflammatory activities. Numerous baicalein derivatives, including 5,6,7-trimethoxyflavone, have been synthesized with the aim of enhancing its inherent biological activities. In the present work, new flavones, possessing an N-aroylamine-substituent on the B-ring, were synthesized to improve the cytotoxicity of baicalein and 5,6,7-trimethoxyflavone against human cancer cell lines. The majority of the flavones synthesized exhibited greater cytotoxicity than baicalein and 5,6,7-trimethoxyflavone against HepG2 and MCF-7 cells. Among them, compounds 5n, possessing a 3-methoxybenzoylamino group, exhibited great cytotoxic effects on HepG2 (GI50=7.06μM) and MCF-7 (GI50=7.67μM) cells. In contrast, N-aroylamine-substituted 5-hydroxy-6,7-dimethoxyflavone derivatives showed greater cytotoxicity against MCF-7 than HepG2 cells, indicating that the replacement of a 5-methoxy group on the A-ring with a 5-hydroxy group has a marked influence on the cytotoxicity profile. PMID:27503682

  10. 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.

  11. Selection of tracers for oil and gas evaluation

    International Nuclear Information System (INIS)

    The importance of tracer tests in reservoir descriptions is increasingly acknowledged by reservoir engineers as a method to obtain valuable dynamic information from the reservoir. The report describes the ''state-of-the art'' on tracer technology for interwell investigations. Experiences gained from a number of reported field tracer tests are reviewed, and results from detailed laboratory investigations on the static and dynamic behavior of various tracer molecules are discussed. A critical evaluation of the applicability of the various identified tracers is provided. Present and future trends in the development of tracer technology for reservoir description are sketched. 64 refs., 12 figs., 2 tabs

  12. Synthesis and biological evaluation of a novel pentagastrin-toxin conjugate designed for a targeted prodrug mono-therapy of cancer.

    Science.gov (United States)

    Tietze, Lutz F; Panknin, Olaf; Krewer, Birgit; Major, Felix; Schuberth, Ingrid

    2008-05-01

    A novel carbamate prodrug 2 containing a pentagastrin moiety was synthesized. 2 was designed as a detoxified analogue of the highly cytotoxic natural antibiotic duocarmycin SA (1) for the use in a targeted prodrug monotherapy of cancers expressing cholecystokinin (CCK-B)/gastrin receptors. The synthesis of prodrug 2 was performed using a palladium-catalyzed carbonylation of bromide 6, followed by a radical cyclisation to give the pharmacophoric unit 10, coupling of 10 to the DNA-binding subunit 15 and transformation of the resulting seco-drug 3b into the carbamate 2 via addition of a pentagastrin moiety.

  13. [Cancer].

    Science.gov (United States)

    de la Peña-López, Roberto; Remolina-Bonilla, Yuly Andrea

    2016-09-01

    Cancer is a group of diseases which represents a significant public health problem in Mexico and worldwide. In Mexico neoplasms are the second leading cause of death. An increased morbidity and mortality are expected in the next decades. Several preventable risk factors for cancer development have been identified, the most relevant including tobacco use, which accounts for 30% of the cancer cases; and obesity, associated to another 30%. These factors, in turn, are related to sedentarism, alcohol abuse and imbalanced diets. Some agents are well knokn to cause cancer such as ionizing radiation, viruses such as the papilloma virus (HPV) and hepatitis virus (B and C), and more recently environmental pollution exposure and red meat consumption have been pointed out as carcinogens by the International Agency for Research in Cancer (IARC). The scientific evidence currently available is insufficient to consider milk either as a risk factor or protective factor against different types of cancer. PMID:27603890

  14. 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.

  15. 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.

  16. 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.

  17. Planetary Nebulae as Mass Tracers in Galaxies

    OpenAIRE

    Romanowsky, Aaron J.

    2006-01-01

    Planetary nebula are useful kinematic tracers of the stars in all galaxy types. I review recent observationally-driven developments in the study of galaxy mass profiles. These have yielded surprising results on spiral galaxy disk masses and elliptical galaxy halo masses. A key remaining question is the coupling between PNe and the underlying stellar populations.

  18. Using radioactive tracer technique in municipal hygiene

    International Nuclear Information System (INIS)

    Work of the A. N. Syrsin Institute of General and Municiapl Hygiene using raidoactive tracers is reviewed. The studies include research on protein metabolism in the living organism following action of unfavorable factors of the environment; determination of the paths of introduction into the organism of substances with an alien composition; and study of the rate of resorption of subcutaneous papuli. Results are shown of radioactive-tracer studies on the mechanism of action of poisonous substances on the living organism and of migration of alien chemical compounds in the organism and in objects in the environment. It is concluded that the radioactive tracer method has wide application in municipal hygiene and sanitary microbiology. The absence of laborious operations, economy of time, precision of the experiments, and the possibility of obtaining additional information on the mechanism of action of poisonous substances on the organism and the low cost of such studies compared with other methods makes the radioactive tracer method economically attractive. The studies made show the various types of use of the method in municipal hygiene and sanitary microbiology

  19. 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...

  20. 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.

  1. Forbidden calcium lines as disc tracers

    CERN Document Server

    Aret, Anna

    2015-01-01

    Forbidden emission lines are particularly valuable disc tracers, because their profiles reflect the kinematics within their formation region. Here we present a short excerpt from the results of a spectroscopic survey of evolved massive stars surrounded by high-density discs.

  2. 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.

  3. 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...

  4. 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.)

  5. Berberine inhibits androgen synthesis by interaction with aldo-keto reductase 1C3 in 22Rv1 prostate cancer cells.

    Science.gov (United States)

    Tian, Yuantong; Zhao, Lijing; Wang, Ye; Zhang, Haitao; Xu, Duo; Zhao, Xuejian; Li, Yi; Li, Jing

    2016-01-01

    Aldo-keto reductase family 1 member C3 has recently been regarded as a potential therapeutic target in castrate-resistant prostate cancer. Herein, we investigated whether berberine delayed the progression of castrate-resistant prostate cancer by reducing androgen synthesis through the inhibition of Aldo-keto reductase family 1 member C3. Cell viability and cellular testosterone content were measured in prostate cancer cells. Aldo-keto reductase family 1 member C3 mRNA and protein level were detected by RT-PCR and Western bolt analyses, respectively. Computer analysis with AutoDock Tools explored the molecular interaction of berberine with Aldo-keto reductase family 1 member C3. We found that berberine inhibited 22Rv1 cells proliferation and decreased cellular testosterone formation in a dose-dependent manner. Berberine inhibited Aldo-keto reductase family 1 member C3 enzyme activity, rather than influenced mRNA and protein expressions. Molecular docking study demonstrated that berberine could enter the active center of Aldo-keto reductase family 1 member C3 and form p-p interaction with the amino-acid residue Phe306 and Phe311. In conclusion, the structural interaction of berberine with Aldo-keto reductase family 1 member C3 is attributed to the suppression of Aldo-keto reductase family 1 member C3 enzyme activity and the inhibition of 22Rv1 prostate cancer cell growth by decreasing the intracellular androgen synthesis. Our result provides the experimental basis for the design, research, and development of AKR1C3 inhibitors using berberine as the lead compound. PMID:26698234

  6. Tracer Partitioning in Two-Phase Flow

    Science.gov (United States)

    Sathaye, K.; Hesse, M. A.

    2012-12-01

    The concentration distributions of geochemical tracers in a subsurface reservoir can be used as an indication of the reservoir flow paths and constituent fluid origin. In this case, we are motivated by the origin of marked geochemical gradients in the Bravo Dome natural CO2 reservoir in northeastern New Mexico. This reservoir contains 99% CO2 with various trace noble gas components and overlies the formation brine in a sloping aquifer. It is thought that magmatic CO2 entered the reservoir, and displaced the brine. This displacement created gradients in the concentrations of the noble gases. Two models to explain noble gas partitioning in two-phase flow are presented here. The first model assumes that the noble gases act as tracers and uses a first order non-linear partial differential equation to compute the volume fraction of each phase along the displament path. A one-way coupled partial differential equation determines the tracer concentration, which has no effect on the overall flow or phase saturations. The second model treats each noble gas as a regular component resulting in a three-component, two-phase system. As the noble gas injection concentration goes to zero, we see the three-component system behave like the one-way coupled system of the first model. Both the analytical and numerical solutions are presented for these models. For the process of a gas displacing a liquid, we see that a noble gas tracer with greater preference for the gas phase, such as Helium, will move more quickly along the flowpath than a heavier tracer that will more easily enter the liquid phase, such as Argon. When we include partial miscibility of both the major and trace components, these differences in speed are shown in a bank of the tracer at the saturation front. In the three component model, the noble gas bank has finite width and concentration. In the limit where the noble gas is treated as a tracer, the width of the bank is zero and the concentration increases linearly

  7. 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

  8. 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

  9. Resistance absorption of some groundwater tracers in porous media

    Science.gov (United States)

    Jafari, Fateme

    2010-05-01

    Absorption of tracer to the aquifer material is among the most important factors which should be considered when a tracing program is considered. In this study, the absorption of the tracer into the porous media is analyzed experimentally for some of the most important and applied tracers as uranine, rhodamine B, eosin, potassium permanganate, sodium chloride and potassium chloride. For each tracer, effect of initial tracer concentration and percentage of fine grain sediments on tracer absorption in porous media is analyzed. According to the final results, rhodamine B and potassium permanganate have the less resistance against absorption to aquifer material, whilst eosin and uranine are the most resistant tracers among the examined ones. Key Words: Tracer, Absorption, Aquifer, Column Method

  10. 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)

  11. Improved tumor identification using dual tracer molecular imaging in fluorescence guided brain surgery

    Science.gov (United States)

    Xu, Xiaochun; Torres, Veronica; Straus, David; Brey, Eric M.; Byrne, Richard W.; Tichauer, Kenneth M.

    2015-03-01

    Brain tumors represent a leading cause of cancer death for people under the age of 40 and the probability complete surgical resection of brain tumors remains low owing to the invasive nature of these tumors and the consequences of damaging healthy brain tissue. Molecular imaging is an emerging approach that has the potential to improve the ability for surgeons to correctly discriminate between healthy and cancerous tissue; however, conventional molecular imaging approaches in brain suffer from significant background signal in healthy tissue or an inability target more invasive sections of the tumor. This work presents initial studies investigating the ability of novel dual-tracer molecular imaging strategies to be used to overcome the major limitations of conventional "single-tracer" molecular imaging. The approach is evaluated in simulations and in an in vivo mice study with animals inoculated orthotopically using fluorescent human glioma cells. An epidermal growth factor receptor (EGFR) targeted Affibody-fluorescent marker was employed as a targeted imaging agent, and the suitability of various FDA approved untargeted fluorescent tracers (e.g. fluorescein & indocyanine green) were evaluated in terms of their ability to account for nonspecific uptake and retention of the targeted imaging agent. Signal-to-background ratio was used to measure and compare the amount of reporter in the tissue between targeted and untargeted tracer. The initial findings suggest that FDA-approved fluorescent imaging agents are ill-suited to act as untargeted imaging agents for dual-tracer fluorescent guided brain surgery as they suffer from poor delivery to the healthy brain tissue and therefore cannot be used to identify nonspecific vs. specific uptake of the targeted imaging agent where current surgery is most limited.

  12. 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...

  13. Tracer Interpretation Using Temporal Moments on a Spreadsheet

    Energy Technology Data Exchange (ETDEWEB)

    G. Michael Shook; J. Hope Forsmann

    2005-06-01

    This report presents a method for interpreting geothermal tracer tests. The method is based on the first temporal moment (mean residence time) of the tracer in the subsurface. The individual steps required to interpret a tracer test are reviewed and discussed. And an example tracer test directs the user through the interpretation method. An Excel spreadsheet application of the interpretation method is a companion document to this report.

  14. Thermal tracer tests for characterizing a shallow alluvial aquifer

    OpenAIRE

    Wildemeersch, Samuel; Klepikova, Maria; Jamin, Pierre; Orban, Philippe; Hermans, Thomas; Brouyère, Serge; Dassargues, Alain

    2014-01-01

    Using heat as an active tracer in different types of aquifers is a topic of increasing interest [e.g. Vandenbohede et al.; 2008, Wagner et al., 2013; Read et al., 2013]. In this study, we investigate the potential interest of coupling heat and solute tracer tests for characterization of a shallow alluvial aquifer. A thermal tracer test was conducted in the alluvial aquifer of the Meuse River, Belgium. The tracing experiment consisted in simultaneously injecting heated water and a dye tracer i...

  15. Diffusion weighted MRI and 18F-FDG PET/CT in non-small cell lung cancer (NSCLC): Does the apparent diffusion coefficient (ADC) correlate with tracer uptake (SUV)?

    Energy Technology Data Exchange (ETDEWEB)

    Regier, M., E-mail: mregier@uke.uni-hamburg.de [Center for Radiology and Endoscopy, Department of Diagnostic and Interventional Radiology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg (Germany); Derlin, T. [Center for Radiology and Endoscopy, Department of Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg (Germany); Schwarz, D.; Laqmani, A.; Henes, F.O.; Groth, M.; Buhk, J.-H. [Center for Radiology and Endoscopy, Department of Diagnostic and Interventional Radiology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg (Germany); Kooijman, H. [Philips Healthcare, Clinical Application, Luebeckertordamm 5, 20099 Hamburg (Germany); Adam, G. [Center for Radiology and Endoscopy, Department of Diagnostic and Interventional Radiology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg (Germany)

    2012-10-15

    Introduction: To investigate the potential correlation of the apparent diffusion coefficient assessed by diffusion-weighted MRI (DWI) and glucose metabolism determined by the standardized uptake value (SUV) at 18F-FDG PET/CT in non-small cell lung cancer (NSCLC). Materials and methods: 18F-FDG PET/CT and DWI (TR/TE, 2000/66 ms; b-values, 0 and 500 s/mm{sup 2}) were performed in 41 consecutive patients with histologically verified NSCLC. Analysing the PET-CT data calculation of the mean (SUV{sub mean}) and maximum (SUV{sub max}) SUV was performed. By placing a region-of-interest (ROI) encovering the entire tumor mean (ADC{sub mean}) and minimum ADC (ADC{sub min}) were determined by two independent radiologists. Results of 18F-FDG PET-CT and DWI were compared on a per-patient basis. For statistical analysis Pearson's correlation coefficient, Bland–Altman and regression analysis were assessed. Results: Data analysis revealed a significant inverse correlation of the ADC{sub min} and SUV{sub max} (r = −0.46; p = 0.032). Testing the correlation of the ADC{sub min} and SUV{sub max} for each histological subtype separately revealed that the inverse correlation was good for both adenocarcinomas (r = −0.47; p = 0.03) and squamouscell carcinomas (r = −0.71; p = 0.002), respectively. No significant correlation was found for the comparison of ADC{sub min} and SUV{sub mean} (r = −0.29; p = 0.27), ADC{sub mean} vs. SUV{sub mean} (r = −0.28; p = 0.31) or ADC{sub mean} vs. SUV{sub max} (r = −0.33; p = 0.23). The κ-value of 0.88 indicated a good agreement between both observers. Conclusion: This preliminary study is the first to verify the relation between the SUV and the ADC in NSCLC. The significant inverse correlation of these two quantitative imaging approaches points out the association of metabolic activity and tumor cellularity. Therefore, DWI with ADC measurement might represent a new prognostic marker in NSCLC.

  16. Industrial tracer application in people's republic of china

    International Nuclear Information System (INIS)

    A number of important applications of radioisotopes and their compounds used as tracers in petroleum industry, metallurgical industry, mechanical industry, chemical industry, electronic industry, hydrology and water conservancy in China are introduced in this paper. And the tracer technique applied to entomology is also mentioned. The industrial tracer applications are successful and beneficial in People's Republic of China from the examples given. (author)

  17. Natural tracer profiles across argillaceous formations

    Energy Technology Data Exchange (ETDEWEB)

    Mazurek, Martin, E-mail: mazurek@geo.unibe.ch [Rock-Water Interaction, Institute of Geological Sciences, University of Bern (Switzerland); Alt-Epping, Peter [Rock-Water Interaction, Institute of Geological Sciences, University of Bern (Switzerland); Bath, Adrian [Intellisci, Willoughby on the Wolds, Loughborough LE12 6SZ (United Kingdom); Gimmi, Thomas [Rock-Water Interaction, Institute of Geological Sciences, University of Bern (Switzerland)] [Paul Scherrer Institut, 5232 Villigen PSI (Switzerland); Niklaus Waber, H. [Rock-Water Interaction, Institute of Geological Sciences, University of Bern (Switzerland); Buschaert, Stephane [Andra, Parc de la Croix Blanche, 92298 Chatenay-Malabry Cedex (France); Canniere, Pierre De; Craen, Mieke De [SCK-CEN, 2400 Mol (Belgium); Gautschi, Andreas [Nagra, 5430 Wettingen (Switzerland); Savoye, Sebastien [IRSN, 92262 Fontenay-aux-Roses Cedex (France); Vinsot, Agnes [Andra, Parc de la Croix Blanche, 92298 Chatenay-Malabry Cedex (France); Wemaere, Isabelle [SCK-CEN, 2400 Mol (Belgium); Wouters, Laurent [Ondraf/Niras, 1210 Brussels (Belgium)

    2011-07-15

    Highlights: > Solute transport processes in clay and shale formations at nine sites are examined. > Conservative pore-water tracers (e.g. Cl{sup -}, {delta}{sup 18}O, {delta}{sup 2}H, He) show regular profiles. > These indicate the dominance of diffusive transport over times of 10{sup 5}-10{sup 6} years. > The contribution of vertical advection to transport is limited or negligible. > Modelled evolution times are in line with independent palaeo-hydrogeological data. - Abstract: Argillaceous formations generally act as aquitards because of their low hydraulic conductivities. This property, together with the large retention capacity of clays for cationic contaminants, has brought argillaceous formations into focus as potential host rocks for the geological disposal of radioactive and other waste. In several countries, programmes are under way to characterise the detailed transport properties of such formations at depth. In this context, the interpretation of profiles of natural tracers in pore waters across the formations can give valuable information about the large-scale and long-term transport behaviour of these formations. Here, tracer-profile data, obtained by various methods of pore-water extraction for nine sites in central Europe, are compiled. Data at each site comprise some or all of the conservative tracers: anions (Cl{sup -}, Br{sup -}), water isotopes ({delta}{sup 18}O, {delta}{sup 2}H) and noble gases (mainly He). Based on a careful evaluation of the palaeo-hydrogeological evolution at each site, model scenarios are derived for initial and boundary pore-water compositions and an attempt is made to numerically reproduce the observed tracer distributions in a consistent way for all tracers and sites, using transport parameters derived from laboratory or in situ tests. The comprehensive results from this project have been reported in . Here the results for three sites are presented in detail, but the conclusions are based on model interpretations of the

  18. 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

  19. 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...... for the perfect neuroendocrine tumor imaging tracer. (68)Ga-labeled tracers coupled to synthetic somatostatin analogs with differences in affinity for the five somatostatin receptor subtypes are now widely applied in Europe. Comparison of sensitivity between the most used tracers - (68)Ga-DOTA-Tyr3-octreotide...

  20. Sleep and cancer: Synthesis of experimental data and meta-analyses of cancer incidence among some 1,500,000 study individuals in 13 countries.

    Science.gov (United States)

    Erren, T C; Morfeld, P; Foster, R G; Reiter, R J; Groß, J V; Westermann, I K

    2016-01-01

    Sleep and its impact on physiology and pathophysiology are researched at an accelerating pace and from many different angles. Experiments provide evidence for chronobiologically plausible links between chronodisruption and sleep and circadian rhythm disruption (SCRD), on the one hand, and the development of cancer, on the other. Epidemiological evidence from cancer incidence among some 1 500 000 study individuals in 13 countries regarding associations with sleep duration, napping or "poor sleep" is variable and inconclusive. Combined adjusted relative risks (meta-RRs) for female breast cancer, based on heterogeneous data, were 1.01 (95% CI: 0.97-1.06). Meta-RRs for cancers of the colorectum and of the lung in women and men and for prostate cancer were 1.08 (95% CI: 1.03-1.13), 1.11 (95% CI: 1.00-1.22) and 1.05 (95% CI: 0.83-1.33), respectively. The significantly increased meta-RRs for colorectal cancer, based on homogeneous data, warrant targeted study. However, the paramount epidemiological problem inhibiting valid conclusions about the associations between sleep and cancer is the probable misclassification of the exposures to facets of sleep over time. Regarding the inevitable conclusion that more research is needed to answer How are sleep and cancer linked in humans? we offer eight sets of recommendations for future studies which must take note of the complexity of multidirectional relationships. PMID:27003385

  1. Into the regolith: digging for hydrological tracers

    Science.gov (United States)

    Moragues-Quiroga, Cristina; Hissler, Christophe; Chabaux, François; Legout, Arnaud; Stille, Peter

    2016-04-01

    The mineralogical and trace element composition of regoliths is a source of potential tracers of water behaviour in catchment systems. We propose an assessment of the most suitable spatial tracers for water collection, mixing, storage and release processes by incorporating geochemical signatures derived from trace and major elements to the description of sources and pathways of water contributions in the stream. To date, stable isotopes are widely used to trace water sources and water transit times but they are still missing a complementary tool which allows for the identification of end-members and the understanding of mixing processes within the regolith. Trace elements are known to be powerful and precise geochemical tracers of environmental processes and, therefore, they can be useful indicators of the spatial origin and evolution of regolith materials and water chemistry. We studied a whole slate regolith profile for its mineralogical, major and trace element composition. The different regolith components were subjected to a leaching experiment in order to identify chemical zonations within and assess the potential elements mobility. Rain, soil, stream and ground waters were collected at the same location than the regolith system over 4 years, analysed for their trace and major elements composition and compared to regolith and regolith leachates data. The results deliver valuable information on exchange processes at the water-mineral interface in the different zones of the regolith. The geochemical scheme of a complete regolith and the waters it holds is here presented to prove the efficiency of trace and major elements as complementary hydrological and geochemical tracers of water migration throughout a regolith till the stream.

  2. 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.

  3. Synthesis and biological evaluation of copper-64 radiolabeled [DUPA-6-Ahx-(NODAGA)-5-Ava-BBN(7-14)NH2], a novel bivalent targeting vector having affinity for two distinct biomarkers (GRPr/PSMA) of prostate cancer

    International Nuclear Information System (INIS)

    Gastrin-releasing peptide receptors (GRPr) and prostate-specific membrane antigen (PSMA) are two identifying biomarkers expressed in very high numbers on prostate cancer cells and could serve as a useful tool for molecular targeting and diagnosis of disease via positron-emission tomography (PET). The aim of this study was to produce the multipurpose, bivalent [DUPA-6-Ahx-(64Cu-NODAGA)-5-Ava-BBN(7-14)NH2] radioligand for prostate cancer imaging, where DUPA = (2-[3-(1,3-dicarboxypropyl)-ureido]pentanedioic acid), a small-molecule, PSMA-targeting probe, 6Ahx = 6-aminohexanoic acid, 5-Ava = 5-aminovaleric acid, NODAGA = [2-(4,7-biscarboxymethyl)-1,4,7-(triazonan-1-yl)pentanedioic acid] (a derivative of NOTA (1,4,7-triazacyclononane-1,4,7-triacetic acid)), and BBN(7-14)NH2 = bombesin, a GRPr-specific peptide targeting probe. Methods: The PSMA/GRPr dual targeting ligand precursor [DUPA-6-Ahx-K-5-Ava-BBN(7-14)NH2], was synthesized by solid-phase and manual peptide synthesis, after which NODAGA was added via manual conjugation to the ε-amine of lysine (K). The new bivalent GRPr/PSMA targeting vector was purified by reversed-phase high performance liquid chromatography (RP-HPLC), characterized by electrospray-ionization mass spectrometry (ESI-MS), and metallated with 64CuCl2 and natCuCl2. The receptor binding affinity was evaluated in human, prostate, PC-3 (GRPr-positive) and LNCaP (PSMA-positive) cells and the tumor-targeting efficacy determined in severe combined immunodeficient (SCID) and athymic nude mice bearing PC-3 and LNCaP tumors. Whole-body maximum intensity microPET/CT images of PC-3/LNCaP tumor-bearing mice were obtained 18 h post-injection (p.i.). Results: Competitive binding assays in PC-3 and LNCaP cells indicated high receptor binding affinity for the [DUPA-6-Ahx-(natCu-NODAGA)-5-Ava-BBN(7-14)NH2] conjugate. MicroPET scintigraphy in PC-3/LNCaP tumor-bearing mice indicated that xenografted tumors were visible at 18 h p.i. with collateral, background

  4. Tracer techniques in plant breeding programmes

    International Nuclear Information System (INIS)

    Tracer techniques may be used as a tool in plant breeding programmes either to help in the choice of parental combinations with complementary advantages or in the selection of desirable plants within the segregating populations. The second application is, however, of little practical application as the techniques involved are mostly too tedious to be used on the large populations with which the plant breeder must deal, and frequently involve unacceptable destructive sampling of his material. The physiological analysis of potential parents is of considerable importance, particularly in the improvement of crops to be grown in more fully developed countries with advanced agricultural systems. Techniques using radioactive tracers and radiation-emitting sources such as the neutron probe have played a considerable part in this work. They have been used by cereal breeders to measure photosynthesis either of individual leaves, or of undisturbed crop canopies, and by breeders of many crops in the study of the translocation of the products of photosynthesis within the plant. They have also been used in studies of the effects of plant diseases on translocation patterns, thus identifying limiting factors for which the breeder should select. Radioactive tracers have also been used in estimating varietal differences in root growth and distribution, but the results obtained from such experiments have indicated that environmental differences are greater than those between genotypes. Differences in water uptake have, however, been demonstrated using the neutron probe, though these differences appear to be much influenced by differences in the water economy of the aerial parts. (author)

  5. Radon diagnostics and tracer gas measurements

    International Nuclear Information System (INIS)

    An outline is presented of the tracer gas technique, which is used for continuous measurements of air ventilation rate (generally time-varying) and for simultaneous estimation of air ventilation rate and radon entry rate, and some of its limitations are discussed. The performance of this technique in the calculation of the air ventilation rate is demonstrated on real data from routine measurements. The potential for air ventilation rate estimation based on radon measurements only is discussed. A practical application is described of the tracer gas technique to a simultaneous estimation of the air ventilation rate and radon entry rate in a real house where the effectiveness of radon remedy was tested. The following main advantages of the CO tracer gas techniques are stressed: (i) The averaging method continuous determination of the ventilation rate with good accuracy (≤ 20 %). (ii) The newly presented and verified method based on simultaneous measurements of radon concentration and CO gas concentration enables separate continuous measurements of the radon entry rate and ventilation rate. The results of comparative measurements performed with the aim to estimate the inaccuracy in determination of radon entry rate showed acceptable and good agreement up to approximately 10 %. The results of comparative measurements performed with the aim to estimate the mutual commensuration of the method to the determination of the ventilation rate confirmed the expected unreliability the two parametric non-linear regression method, which is the most frequently used method in radon diagnostic in the Czech Republic

  6. 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...

  7. The ATLAS DDM Tracer monitoring framework

    Science.gov (United States)

    Zang, Dongsong; Garonne, Vincent; Barisits, Martin; Lassnig, Mario; Stewart, Graeme Andrew; Molfetas, Angelos; Beermann, Thomas

    2012-12-01

    The DDM Tracer monitoring framework is aimed to trace and monitor the ATLAS file operations on the Worldwide LHC Computing Grid. The volume of traces has increased significantly since the framework was put in production in 2009. Now there are about 5 million trace messages every day and peaks can be near 250Hz, with peak rates continuing to climb, which gives the current structure a big challenge. Analysis of large datasets based on on-demand queries to the relational database management system (RDBMS), i.e. Oracle, can be problematic, and have a significant effect on the database's performance. Consequently, We have investigated some new high availability technologies like messaging infrastructure, specifically ActiveMQ, and key-value stores. The advantages of key value store technology are that they are distributed and have high scalability; also their write performances are usually much better than RDBMS, all of which are very useful for the Tracer monitoring framework. Indexes and distributed counters have been also tested to improve query performance and provided almost real time results. In this paper, the design principles, architecture and main characteristics of Tracer monitoring framework will be described and examples of its usage will be presented.

  8. 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 ...

  9. Selective synthesis of either enantiomer of an anti-breast cancer agent via a common enantioenriched intermediate

    Science.gov (United States)

    Johnson, Aaron George; Tranquilli, Marissa M.; Harris, Michael R.; Jarvo, Elizabeth R.

    2015-01-01

    A stereoselective synthesis of a bioactive triarylmethane is described. Key to the synthesis is a nickel-catalyzed Suzuki-Miyaura coupling which proceeds with retention at the benzylic center. This method is complementary to our previously reported nickel-catalyzed Kumada coupling which proceeds with inversion. Together, the two methods allow for efficient access to either enantiomer of biologically relevant triarylmethanes from a common enantioenriched intermediate. PMID:26085695

  10. 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

  11. Design, synthesis and evaluation of 6-aryl-indenoisoquinolone derivatives dual targeting ERα and VEGFR-2 as anti-breast cancer agents.

    Science.gov (United States)

    Tang, Zhichao; Wu, Chengzhe; Wang, Tianlin; Lao, Kejing; Wang, Yejun; Liu, Linyi; Muyaba, Moses; Xu, Pei; He, Conghui; Luo, Guoshun; Qian, Zhouyang; Niu, Shaoxiong; Wang, Lijun; Wang, Ying; Xiao, Hong; You, Qidong; Xiang, Hua

    2016-08-01

    The estrogen receptors have played important roles in breast cancer development and progression. Selective estrogen receptor modulators, such as Tamoxifen, have showed great benefits in the treatment and prevention of breast cancer. But the disadvantages of induction of endometrial cancer and drug resistance have limited their use. Multiple ligand which act at multiple biomolecular targets may exert favorable advantages of improved efficacy with lower incidence of side effects. In this work, we described the synthesis and evaluation of a series of 6-aryl-indenoisoquinolone derivatives as dual ERα and VEGFR-2 inhibitors. These compounds presented good ERα binding affinity and ERα antagonistic activity, as well as potent VEGFR-2 inhibitory potency. They also possessed excellent anti-proliferative activities against MCF-7, MDA-MB-231, Ishikawa and HUVEC cell lines. Further investigation of selective compound 21c showed that it was able to inhibit the activation of VEGFR-2 and the signaling transduction of Raf-1/MAPK/ERK pathway in MCF-7 cells. PMID:27176944

  12. 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.

  13. 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.

  14. An atom size effect in tracer diffusion

    International Nuclear Information System (INIS)

    Published diffusion data permit an extensive comparison to be made between tracer diffusion coefficients, D, in Pb and in α-Zr, at 0.6 Tsub(m), where Tsub(m)(K) is the melting temperature of the host metal. For these metals, a striking correlation is found between D and the metallic radius, r, of the corresponding tracer element; except for the smallest r values, the correlation may be expressed in the general form: 1g D = A + exp(- br + c), where A, b and c are individual constants for each host metal. There is, for tracer diffusion in Pb, sufficient experimental data to permit the evaluation of an additional relationship between the pre-exponential factor Dsub(O), and the activation enthalpy, ΔH, in the usual expression D = D0 exp(- ΔH/RT), describing the temperature dependence of D. A combination of these relationships allows the evaluation of expressions for D0 and ΔH in which r is the only variable. Derived relations between D0 and ΔH, and ΔH and ΔH and r, are, respectively, D0 = 2.0 x 10-4 exp (0.345 ΔH)cm2s-1, and ΔH = 30.8 - exp (8.65 - 4.04 r), in which the units of ΔH and r are kcal mol-1 and A respectively. In order to compare tracer diffusion in these 'open' metals (i.e. metals with a relatively large metallic/ionic radius ratio) with tracer diffusion in a 'full' metal, values of D at 0.6 Tsub(m) have been calculated from published data for diffusion in Cu. Again it is found that 1g D tends to display an exponential dependence on r; in contrast to the results for the 'open' metals, however, 1g D is found to increase with r. Expressions derived for D0 and ΔH for diffusion in Cu, corresponding to those given above for Pb, are: D0 = 5.2 x 10-4 exp(0.152 ΔH)cm2s-1 and ΔH 43.1 + exp(17.40 - 11.94 r), in which the units of ΔH and r are as given for Pb. (author)

  15. A Method of Evaluating Atmospheric Models Using Tracer Measurements.

    Science.gov (United States)

    Korain, Darko; Frye, James; Isakov, Vlad

    2000-02-01

    The authors have developed a method that uses tracer measurements as the basis for comparing and evaluating wind fields. An important advantage of the method is that the wind fields are evaluated from the tracer measurements without introducing dispersion calculations. The method can be applied to wind fields predicted by different atmospheric models or to wind fields obtained from interpolation and extrapolation of measured data. The method uses a cost function to quantify the success of wind fields in representing tracer transport. A cost function, `tracer potential,' is defined to account for the magnitude of the tracer concentration at the tracer receptors and the separation between each segment of a trajectory representing wind field transport and each of the tracer receptors. The tracer potential resembles a general expression for a physical potential because the success of a wind field trajectory is directly proportional to the magnitude of the tracer concentration and inversely proportional to its distance from this concentration. A reference tracer potential is required to evaluate the relative success of the wind fields and is defined by the initial location of any trajectory at the source. Then the method is used to calculate continuously the tracer potential along each trajectory as determined by the wind fields in time and space. Increased potential relative to the reference potential along the trajectory indicates good performance of the wind fields and vice versa. If there is sufficient spatial coverage of near and far receptors around the source, then the net tracer potential area can be used to infer the overall success of the wind fields. If there are mainly near-source receptors, then the positive tracer potential area should be used. If the vertical velocity of the wind fields is not available, then the success of the wind fields can be estimated from the vertically integrated area under the tracer potential curve. A trajectory with a maximum

  16. 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…

  17. PMA-SiO2 catalyzed synthesis of indolo[2,3-c]quinolines as potent anti cancer agents.

    Science.gov (United States)

    Srihari, P; Padmabhavani, B; Ramesh, S; Bharath Kumar, Y; Singh, Ashita; Ummanni, R

    2015-06-01

    PMA-SiO2 catalyzed Pictet-Spengler reaction of aryl amine linked to C-3 of the indole and the aryl aldehydes was achieved. In the series of the synthesized compounds, 6b, 10b and 12b were found to be cytotoxic against prostate, lung, breast and cervical cancer cell lines selectively with no significant effect on the growth of the control fibroblast cell line NIH3T3. Further determining their cytotoxic potential we found that 10b and 12b show cell cycle arrest in DU145 prostate cancer cells indicating a role in cell cycle progression. Both the molecules showed effect on decreased phosphorylation of NF-κB on serine 536 residue which is strongly implicated in many different types of cancers. Taken together, the series of indoloquinolines elicit potent anti-cancer potential providing a mean for developing novel indoloquinoline based anti-cancer agents. PMID:25933593

  18. Synthesis and in vitro anti-cancer evaluation of luteinizing hormone-releasing hormone-conjugated peptide.

    Science.gov (United States)

    Deng, Xin; Qiu, Qianqian; Ma, Ke; Huang, Wenlong; Qian, Hai

    2015-11-01

    Luteinizing hormone-releasing hormone (LHRH) is a decapeptide hormone released from the hypothalamus and shows high affinity binding to the LHRH receptors. It is reported that several cancer cells also express LHRH receptors such as breast, ovarian, prostatic, bladder and others. In this study, we linked B1, an anti-cancer peptide, to LHRH and its analogs to improve the activity against cancer cells with LHRH receptor. Biological evaluation revealed that TB1, the peptide contains triptorelin sequence, present favorable anti-cancer activity as well as plasma stability. Further investigations disclosed that TB1 trigger apoptosis by activating the mitochondria-cytochrome c-caspase apoptotic pathway, it also exhibited the anti-migratory effect on cancer cells. PMID:26058357

  19. 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.

  20. 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

  1. 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.

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

    Science.gov (United States)

    Alsalhi, Mohamad S; Devanesan, Sandhanasamy; Alfuraydi, Akram A; Vishnubalaji, Radhakrishnan; Munusamy, Murugan A; Murugan, Kadarkarai; Nicoletti, Marcello; Benelli, Giovanni

    2016-01-01

    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 of green-synthesized AgNPs against five infectious bacteria: Staphylococcus pyogenes (29213), Acinetobacter baumannii (4436), Klebsiella pneumoniae (G455), Salmonella typhi, and Pseudomonas aeruginosa. In addition, we focused on the toxicological effects of AgNPs against hSSC cells and HT115 cells by using in vitro proliferation tests and cell viability assays. Among the different tested concentrations of nanoparticles, doses 10 µg led to increased cytotoxicity. Conclusion Overall, our results highlighted the capacity of P. anisum-synthesized AgNPs as novel and cheap bioreducing agents for eco-friendly nanosynthetical routes. The data confirm the multipurpose potential of plant-borne reducing and stabilizing agents in

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

    Science.gov (United States)

    Alsalhi, Mohamad S; Devanesan, Sandhanasamy; Alfuraydi, Akram A; Vishnubalaji, Radhakrishnan; Munusamy, Murugan A; Murugan, Kadarkarai; Nicoletti, Marcello; Benelli, Giovanni

    2016-01-01

    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 of green-synthesized AgNPs against five infectious bacteria: Staphylococcus pyogenes (29213), Acinetobacter baumannii (4436), Klebsiella pneumoniae (G455), Salmonella typhi, and Pseudomonas aeruginosa. In addition, we focused on the toxicological effects of AgNPs against hSSC cells and HT115 cells by using in vitro proliferation tests and cell viability assays. Among the different tested concentrations of nanoparticles, doses 10 µg led to increased cytotoxicity. Conclusion Overall, our results highlighted the capacity of P. anisum-synthesized AgNPs as novel and cheap bioreducing agents for eco-friendly nanosynthetical routes. The data confirm the multipurpose potential of plant-borne reducing and stabilizing agents in

  4. 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...

  5. Synthesis and anti-cancer activity of covalent conjugates of artemisinin and a transferrin-receptor targeting peptide.

    Science.gov (United States)

    Oh, Steve; Kim, Byung Ju; Singh, Narendra P; Lai, Henry; Sasaki, Tomikazu

    2009-02-01

    Artemisinin, a natural product isolated from Artemisia annua L., shows a unique anti-cancer activity by an iron dependent mechanism. Artemisinin was covalently conjugated to a transferrin-receptor targeting peptide, HAIYPRH that binds to a cavity on the surface of transferrin receptor. This enables artemisinin to be co-internalized with receptor-bound transferrin. The iron released from transferrin can activate artemisinin to generate toxic radical species to kill cells. The artemisinin-peptide conjugates showed potent anti-cancer activity against Molt-4 leukemia cells with a significantly improved cancer/normal cells selectivity. PMID:18838215

  6. Magnetic Particle Imaging with Tailored Iron Oxide Nanoparticle Tracers

    OpenAIRE

    Ferguson, R. Matthew; Khandhar, Amit P.; Kemp, Scott J.; Arami, Hamed; Saritas, Emine U.; Croft, Laura R.; Konkle, Justin; Goodwill, Patrick W.; Halkola, Aleksi; Rahmer, Jürgen; Borgert, Jörn; Steven M. Conolly; Krishnan, Kannan M

    2014-01-01

    Magnetic Particle Imaging (MPI) shows promise for medical imaging, particularly in angiography of patients with chronic kidney disease. As the first biomedical imaging technique that truly depends on nanoscale materials properties, MPI requires highly optimized magnetic nanoparticle tracers to generate quality images. Until now, researchers have relied on tracers optimized for MRI T2*-weighted imaging that are suboptimal for MPI. Here, we describe new tracers tailored to MPI's unique physics,...

  7. Atmospheric Gas Tracers in Groundwater: Theory, Sampling. Measurement and Interpretation

    International Nuclear Information System (INIS)

    Some of the atmospheric gasses posses features that are sought in an environmental tracer of hydrogeologic interest. Among these, chlorofluorocarbons, sulfur hegzafluoride, carbon tetrachloride, methyl chloroform, krypton-85 etc. have found increasing use in groundwater age dating studies during the last ten years. This paper explains the theory of their use as tracer and discusses the major concerns as related to their sampling and analyses. Factors affecting their applicability and the approach to interpret tracer gas data is briefly outlined

  8. Lidar Tracking of Multiple Fluorescent Tracers: Method and Field Test

    Science.gov (United States)

    Eberhard, Wynn L.; Willis, Ron J.

    1992-01-01

    Past research and applications have demonstrated the advantages and usefulness of lidar detection of a single fluorescent tracer to track air motions. Earlier researchers performed an analytical study that showed good potential for lidar discrimination and tracking of two or three different fluorescent tracers at the same time. The present paper summarizes the multiple fluorescent tracer method, discusses its expected advantages and problems, and describes our field test of this new technique.

  9. Tracer test feasibility assessment : Frongoch Mine tailings lagoon

    OpenAIRE

    Maurice, L.; B. Palumbo-Roe; Williams, A. T.; Banks, V.J.; Lapworth, D. J.

    2012-01-01

    The feasibility of tracer testing at the Frongoch Mine site was investigated during a two day site visit. A walkover survey identified a potential tracer injection point where a surface stream sinks into tailings deposits. Water discharges through a culvert approximately 50 m from the sinking stream. The origin of the water in the culvert is unknown but it is thought to drain the tailings area. Tracer testing could be used to determine whether this is the case. A successful tra...

  10. 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

  11. Amino acid containing thapsigargin analogues deplete androgen receptor protein via synthesis inhibition and induce the death of prostate cancer cells

    DEFF Research Database (Denmark)

    Griend, Donald J Vander; Antony, Lizamma; Dalrymple, Susan L;

    2009-01-01

    There are quantitative and/or qualitative mechanisms allowing androgen receptor (AR) growth signaling in androgen ablation refractory prostate cancer cells. Regardless of the mechanism, agents that deplete AR protein expression prevent such AR growth signaling. Thapsigargin (TG) is a highly cell......-penetrant sequiterpene-lactone that once inside cells inhibits (IC(50), approximately 10 nmol/L) critically important housekeeping SERCA 2b calcium pumps in the endoplasmic reticulum. Using a series of five genetically diverse androgen ablation refractory human prostate cancer lines (LNCaP, LAPC-4, VCaP, MDA-PCa-2b, and......-specific proteases, such as prostate-specific antigen and prostate-specific membrane antigen, or cancer-specific proteases, such as fibroblast activation protein, so that toxicity of these prodrugs is selectively targeted to metastatic sites of prostate cancer. Based on these results, these prodrugs are undergoing...

  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. A systematic review and thematic synthesis of quality of life in the informal carers of cancer patients with cachexia

    OpenAIRE

    Darlington, Anne-Sophie; Hopkinson, J.B.; Fitzsimmons, D.; Johnson, C.D.

    2015-01-01

    Background: informal carers of cancer patients with cachexia face additional challenges to those encountered by informal carers in general because of the central role food and eating play in everyday life. Patient weight loss and anorexia, core features of cancer cachexia, are frequent causes of distress in caregivers. Identification of quality of life (QOL) issues can inform the development of interventions for both caregivers and patients, and facilitate communication with healthcare profes...

  14. 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

  15. EFFECTS OF RECOMBINANT TUMOR-NECROSIS-FACTOR (RTNF-ALPHA) IN CANCER - OBSERVATIONS ON THE ACUTE-PHASE PROTEIN REACTION AND IMMUNOGLOBULIN-SYNTHESIS AFTER HIGH-DOSE RECOMBINANT TNF-ALPHA ADMINISTRATION IN ISOLATED LIMB PERFUSIONS IN CANCER-PATIENTS

    NARCIS (Netherlands)

    SWAAK, AJG; LIENARD, D; KOOPS, HS; LEJEUNE, FJ; EGGERMONT, AMM

    1993-01-01

    To obtain insight in the effect of TNF on the synthesis of acute phase proteins like CRP, alpha 1-antitrypsine, alpha 1-acidglycoprotein, C3 and C4 and the immunoglobulins (IgG-M-A), nine cancer patients who were treated with an isolated limb perfusion (ILP) with high dose recombinant TNF-alpha (rTN

  16. 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.

  17. Development and automation of a novel NET-PET tracer: [11C]Me@APPI

    International Nuclear Information System (INIS)

    Introduction: The norepinephrine transporter (NET) is an important target for research in neurology and psychology and is involved in the pathophysiology of many neurodegenerative diseases such as Alzheimer's disease and attention deficient hyperactivity disorder. For visualization of NET abundance and deregulation, a novel PET tracer – [11C]Me@APPI – has been developed. Methods: For precursor synthesis, a 4-step synthesis starting from N-phenyl-o-phenylenediamine was set up. Radiosynthesis was established and optimized using standard methods and subsequently automated in a GE TRACERlabFx C Pro synthesizer. Preclinical testing was performed comprising affinity and selectivity testing on human membranes as well as stability and blood–brain-barrier-penetration using in-vitro models. Results: Precursor molecule (APPI:0) and reference compound (Me@APPI) were synthesized with 26.5% and 21.4% overall yield, respectively. So far, 1.25 ± 0.72 GBq [11C]Me@APPI with 54.35 ± 7.80 GBq/μmol specific activity were produced (n = 11). Affinity of reference compounds was determined as 8.08 ± 1.75 nM for Me@APPI and 19.31 ± 2.91 nM for APPI:0, respectively (n ≥ 9). IAM-chromatography experiments (n = 3) revealed a Pm value of 1.51 ± 0.34 for Me@APPI. Stability testing using human liver microsomes revealed that 99.5% of the tracer was found to be still intact after 60 minutes (n = 4). Conclusion: Present data indicate that [11C]Me@APPI has promising properties to become a clinically useful NET-PET-tracer. Further in-vitro and in-vivo evaluations are currently under way

  18. Molecular markers in breast cancer: new tools in imaging and prognosis

    OpenAIRE

    Vermeulen, J.F.

    2012-01-01

    Breast cancer is the most frequently diagnosed cancer in women. Although breast cancer is mainly diagnosed by mammography, other imaging modalities (e.g. MRI, PET) are increasingly used. The most recent developments in the field of molecular imaging comprise the application of near-infrared fluorescent labeled (NIRF) tracers for detection of breast cancer. Thus far, only a few molecular imaging tracers have been taken to the clinic of which most are suitable for PET. My thesis describes the e...

  19. 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.

  20. 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.

  1. Tracer Dispersion Within an Urban Environment.

    Science.gov (United States)

    Martin, D.; Shallcross, D.; Price, C.; Nickless, G.; Simmonds, P.

    2003-12-01

    The transport and dispersion of pollutants has extremely important implications for the environment on urban, regional and global scales. At the urban level localised emissions of both biogenic and anthropogenic pollutants can directly impact the health of the inhabitants. The DAPPLE (Dispersion of Air Pollutants and their Penetration into the Local Environment) project is a consortium of six universities, which involves a multidisciplinary approach to characterise relatively small-scale urban atmospheric dispersion including wind tunnel modelling, computer simulations, fieldwork and analysis. This work describes the tracer technology used to characterise atmospheric dispersion as well as preliminary results from the first tracer release experiment in Central London. A steady state finite duration release of both perfluoromethylcyclohexane (PMCH) and Sulfur Hexafluoride (SF6 ) was performed as part of the first DAPPLE campaign. These compounds were released over a fifteen-minute integrated time period with the SF6 release staggered one and a half minutes behind the PMCH. The low background concentrations of PMCH (~ 5 x 10-3 pptv) and SF6 (~5pptv) along with non-depositing and non-reactive characteristics allow for the implementation of near ideal fluid dynamic experiments. Sampling consists of a multiport ladder fitting with solenoid valves onto which a succession of sampling bags is attached. These are electrically actuated in sequential order with an integrated sampling time of three minutes. The samplers are placed at various receptor positions in the DAPPLE zone in predefined positions designed to best validate these model simulated meteorological dispersion processes. Analysis of PMCH is carried out using sample enrichment on carbon based adsorbents, separation by capillary Gas Chromatography and Negative Ion Chemical Ionisation Mass Spectrometry detection (GC-MS-NICI). SF6 concentrations are determined using fixed volume loop injections with Gas

  2. 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.

  3. Methane emission quantification from landfills using a double tracer approach

    DEFF Research Database (Denmark)

    Scheutz, Charlotte; Samuelsson, J.; Fredenslund, Anders Michael;

    2007-01-01

    A tracer method was successfully used for quantification of the whole methane (CH4) emission from Fakse landfill. By using two different tracers the emission from different sections of the landfill could be quantified. Furthermore, is was possible to determine the emissions from local on site...

  4. 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...

  5. Chemical tracers in Hybla Gold working room. Final report

    International Nuclear Information System (INIS)

    Chemical tracers were placed in the working room for the Hybla Gold event to aid in diagnosing flow of high-energy gases down expanding pipes leading from the room. If post-shot reentry is made, the tracers could provide valuable knowledge concerning pipe closure, mixing of gases from various locations, and volume of gas flow into various sizes of pipes

  6. Dispersion of charged tracers in charged porous media

    NARCIS (Netherlands)

    B. Rotenberg; I. Pagonabarraga; D. Frenkel

    2008-01-01

    We report a lattice-Boltzmann scheme to compute the dispersion of charged tracers in charged porous media under the combined effect of advection, diffusion and electro-migration. To this end, we extend the moment propagation approach, introduced to study the dispersion of neutral tracers (Lowe C. an

  7. Tuning structure and mobility of solvation shells surrounding tracer additives.

    Science.gov (United States)

    Carmer, James; Jain, Avni; Bollinger, Jonathan A; van Swol, Frank; Truskett, Thomas M

    2015-03-28

    Molecular dynamics simulations and a stochastic Fokker-Planck equation based approach are used to illuminate how position-dependent solvent mobility near one or more tracer particle(s) is affected when tracer-solvent interactions are rationally modified to affect corresponding solvation structure. For tracers in a dense hard-sphere fluid, we compare two types of tracer-solvent interactions: (1) a hard-sphere-like interaction, and (2) a soft repulsion extending beyond the hard core designed via statistical mechanical theory to enhance tracer mobility at infinite dilution by suppressing coordination-shell structure [Carmer et al., Soft Matter 8, 4083-4089 (2012)]. For the latter case, we show that the mobility of surrounding solvent particles is also increased by addition of the soft repulsive interaction, which helps to rationalize the mechanism underlying the tracer's enhanced diffusivity. However, if multiple tracer surfaces are in closer proximity (as at higher tracer concentrations), similar interactions that disrupt local solvation structure instead suppress the position-dependent solvent dynamics. PMID:25833590

  8. New SPECT and PET dementia tracers

    International Nuclear Information System (INIS)

    Single photon emission tomography (SPECT) and positron emission tomography (PET) are techniques to study in vivo neurotransmitter systems, neuro inflammation and amyloid deposits in normal human brain and in dementia. These methods used to explore the integrity of dopaminergic, cholinergic and serotonergic systems in Alzheimer's disease and in other dementias allowed to understand how the neurotransmission was modified in these disorders. Progress in the understanding of pathophysiological and clinical signs of dementia requires an evolution of the radioligands used to carry out an increasingly early and differential diagnosis in addition to monitoring the progression of disease and the effects of therapies. New emerging radiotracers for neuro inflammation or amyloid deposits are essential. In this article, new SPECT and PET tracers are presented. (authors)

  9. 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.

  10. National Biomedical Tracer Facility. Project definition study

    International Nuclear Information System (INIS)

    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-, H+, and D+). The proposed NBTF facility includes an 80 MeV, 1 mA H- cyclotron that will produce proton-induced (neutron deficient) research isotopes

  11. Use of radioactive tracers in chemical reactions

    International Nuclear Information System (INIS)

    A method for the determination of small quantities of nickel using radioactive tracers is presented. An analytical application of the displacement reaction between nickel and zinc ethylenediaminetetraacetate labeled with zinc-65 is pursued. This method is based on the extraction of radioactive zinc displaced by nickel from the zinc chelate into a dithizone-carbon tetracloride solution and the subsequent measurement of the activity of an aliquot of the extract. The method is very sensitive and nickel can be measured in concentrations as small as 0.1μg/ml or even less, depending on the specific activity of the radioreagent used. The precision and the accuracy of the method are determined. The problem of interferences, trying to eliminate them by using masking agents or by means of a previous separation between nickel and other interfering metals, is also investigated

  12. Positron emission tomography tracers for imaging angiogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Haubner, Roland [Medical University Innsbruck, Department of Nuclear Medicine, Innsbruck (Austria); Beer, Ambros J. [Technische Universitaet Muenchen, Department of Nuclear Medicine, Munich (Germany); Wang, Hui [Sichuan University, Department of Radiology, West China Hospital, Chengdu (China); Chen, Xiaoyuan [National Institutes of Health, Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, Bethesda, MD (United States)

    2010-08-15

    Position emission tomography imaging of angiogenesis may provide non-invasive insights into the corresponding molecular processes and may be applied for individualized treatment planning of antiangiogenic therapies. At the moment, most strategies are focusing on the development of radiolabelled proteins and antibody formats targeting VEGF and its receptor or the ED-B domain of a fibronectin isoform as well as radiolabelled matrix metalloproteinase inhibitors or {alpha}{sub v}{beta}{sub 3} integrin antagonists. Great efforts are being made to develop suitable tracers for different target structures. All of the major strategies focusing on the development of radiolabelled compounds for use with positron emission tomography are summarized in this review. However, because the most intensive work is concentrated on the development of radiolabelled RGD peptides for imaging {alpha}{sub v}{beta}{sub 3} expression, which has successfully made its way from bench to bedside, these developments are especially emphasized. (orig.)

  13. 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.

  14. 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.

  15. 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.

  16. Study on Radioecology and Tracer of Iodine-129

    International Nuclear Information System (INIS)

    contaminated regions. The investigations show a strong dependence of childhood thyroid cancer incidence on thyroid exposure dose from short-lived radioiodine isotopes (i.e. 131I, 133I) released from the Chernobyl accident. However, the short half-life of 133I (20.8 h) and 131I (8.02 d) makes the evaluation of thyroid dose from these isotopes not easy. Due to the long half-life of 129I, the 129I concentration in environmental samples can be used to reconstruct the 131I and 133I dose to thyroids. Soil samples from areas in Belarus, Russia and Sweden contaminated by the Chernobyl accident were analysed for 129I and 137Cs by gamma-spectrometry. The atomic ratios of 129I/137Cs ranged from 0.10 to 0.30, with an average of 0.18. It confirmed that the 129I/137Cs ratios could be to reconstruct the deposition pattern of 131I 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 129I and 127I, 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 129I and 127I 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)

  17. Protein-Poly(amino acid) Nanocore-Shell Mediated Synthesis of Branched Gold Nanostructures for Computed Tomographic Imaging and Photothermal Therapy of Cancer.

    Science.gov (United States)

    Sasidharan, Sisini; Bahadur, Dhirendra; Srivastava, Rohit

    2016-06-29

    Anisotropic noble metal nanoparticles especially branched gold nanoparticles with a large absorption cross-section and high molar extinction coefficient have promising applications in biomedical field. However, sophisticated and cumbersome methodologies of synthesis along with toxic precursors pose serious concern for its use. Herein, we report the synthesis of branched gold nanostructures from protein (albumin) nanoparticles by a simple reduction method. Albumin nanoparticles were synthesized by a modified desolvation technique with poly-l-arginine (cationic poly amino acid) substituting the conventional toxic cross-linker, glutaraldehyde. In silico molecular docking was carried out to study the interaction of poly-l-arginine with albumin which revealed its binding to Pocket 1B of the A-chain of albumin. The poly-l-arginine-albumin core-shell nanoparticles of ∼100 nm in size served as a base for attachment of gold ions and its reduction to form 140 nm sized branched gold nanostructures conjugated with glutathione. These gold nanostructures exhibited near-infrared absorption λmax at 800 nm with extreme compatibility toward non cancerous (NIH 3T3), oral epithelial carcinoma (KB) cell lines, and human blood (red blood cells, platelets, and coagulation mechanisms) even up to a high concentration of 250 μg/mL. These structures demonstrated superior computed tomographic (CT) contrast ability and marked photothermal cytotoxicity on KB cells. This study reports for the first time a method to develop blood and cell compatible branched gold nanostructures from protein nanoparticles as a dual CT diagnostic and photothermal therapeutic agent. PMID:27243100

  18. Microwave-assisted aqueous synthesis of new quaternary-alloyed CdSeTeS quantum dots; and their bioapplications in targeted imaging of cancer cells.

    Science.gov (United States)

    Yang, Fengzhao; Xu, Zhancheng; Wang, Jinjie; Zan, Feng; Dong, Chaoqing; Ren, Jicun

    2013-01-01

    In this study, we report for the first time a one-pot approach for the synthesis of new CdSeTeS quaternary-alloyed quantum dots (QDs) in aqueous phase by microwave irradiation. CdCl2 was used as a Cd precursor during synthesis, NaHTe and NaHSe were used as Te and Se precursors and mercaptopropionic acid (MPA) was used as a stabilizer and source of sulfur. A series of quaternary-alloyed QDs of different sizes were prepared. CdSeTeS QDs exhibited a wide emission range from 549 to 709 nm and high quantum yield (QY) up to 57.7 %. Most importantly, the quaternary-alloyed QDs possessed significantly long fluorescence lifetimes > 100 ns as well as excellent photostability. Results of high-resolution transmission electron microscopy (HRTEM), energy dispersive X-ray spectroscopy (EDX) and powder X-ray diffraction (XRD) spectroscopy showed that the nanocrystals possessed a quaternary alloy structure with good crystallinity. Fluorescence correlation spectroscopy (FCS) showed that QDs possessed good water solubility and monodispersity in aqueous solution. Furthermore, CdSeTeS QDs were modified with alpha-thio-omega-carboxy poly(ethylene glycol) (HS-PEG-COOH) and the modified QDs were linked to anti-epidermal growth factor receptor (EGFR) antibodies. QDs with the EGFR antibodies as labeling probes were successfully applied to targeted imaging for EGFR on the surface of SiHa cervical cancer cells. We believe that CdSeTeS QDs can become useful probes for in vivo targeted imaging and clinical diagnosis. PMID:22696455

  19. Collagen synthesis promoting pullulan-PEI-ascorbic acid conjugate as an efficient anti-cancer gene delivery vector.

    Science.gov (United States)

    Ambattu, Lizebona August; Rekha, M R

    2015-08-01

    Cationized pullulan (pullulan-PEI; PP) was synthesized and further modified with an anti-oxidant molecule, ascorbic acid (PPAA) at various ratios. The nanoplexes formed at an optimum ratio of 4:1 was within a size of 150nm and had a zeta potential of 9-14mV. The nanoplexes at this ratio was used for further investigations. The cell internalization and transfection efficiency of these nanoplexes were determined in presence of serum. The internalization and transfection efficiency were found to be unaffected by the presence of fetal bovine serum. Another interesting observation was that this polymer was found to have collagen synthesis promoting property. The collagen synthesis effect of these polymers was quantified and observed that PPAA3 promoted the highest. Transfection efficiency was evaluated by assessing the p53 gene expression in C6 rat glioma cells and cell death was quantified to be 96% by flow cytometry, thus establishing the high efficacy of this polymer. PMID:25933522

  20. Divergent Synthesis of Chondroitin Sulfate Disaccharides and Identification of Sulfate Motifs that Inhibit Triple Negative Breast Cancer

    Science.gov (United States)

    Wei Poh, Zhong; Heng Gan, Chin; Lee, Eric J.; Guo, Suxian; Yip, George W.; Lam, Yulin

    2015-09-01

    Glycosaminoglycans (GAGs) regulate many important physiological processes. A pertinent issue to address is whether GAGs encode important functional information via introduction of position specific sulfate groups in the GAG structure. However, procurement of pure, homogenous GAG motifs to probe the “sulfation code” is a challenging task due to isolation difficulty and structural complexity. To this end, we devised a versatile synthetic strategy to obtain all the 16 theoretically possible sulfation patterns in the chondroitin sulfate (CS) repeating unit; these include rare but potentially important sulfated motifs which have not been isolated earlier. Biological evaluation indicated that CS sulfation patterns had differing effects for different breast cancer cell types, and the greatest inhibitory effect was observed for the most aggressive, triple negative breast cancer cell line MDA-MB-231.

  1. Tumor diagnosis by PET: potential of seven tracers examined in five experimental tumors including an artificial metastasis model

    International Nuclear Information System (INIS)

    The potential of seven tracers for the metabolic imaging of tumors by positron emission tomography was studied using five experimental tumor models. The tracers examined were 2-deoxy-2-[18F]fluoro-D-glucose([18F]FDG), 2-deoxy-2-[18F]fluoro-D-galactose (2-[18F]FdGal) and 2-deoxy-2-[18F]fluoro-L-fucose (2-[18F]FdFuc) for investigating energy metabolism. L-[methyl-11C]Methionine ([11C]Met) and 6-[18F]fluoro-L-fucose (6-[18F]FFuc) were used for assessing protein and glycoprotein synthesis, while [3H]thymidine ([3H]Thd) and 2-deoxy-5'-[18F]fluorouridine ([18F]FdUrd) were used to investigate nucleic acid metabolism. (Author)

  2. Targeting translesion synthesis to facilitate the eradication of ovarian cancer stem cells by platinum-based therapy

    OpenAIRE

    Srivastava, Amit Kumar; Wang, Qi-En

    2015-01-01

    Understanding the mechanisms by which cancer stem cells (CSCs) survive chemotherapy is essential for the development of new therapies. Recently, we demonstrated that ovarian CSCs survive cisplatin treatment through enhanced expression of DNA polymerase η (Pol η). Identification of micro RNA-93 (miR-93) as the regulator of Pol η provides a novel target to improve the outcome of platinum-based therapy.

  3. Targeting translesion synthesis to facilitate the eradication of ovarian cancer stem cells by platinum-based therapy.

    Science.gov (United States)

    Srivastava, Amit Kumar; Wang, Qi-En

    2016-01-01

    Understanding the mechanisms by which cancer stem cells (CSCs) survive chemotherapy is essential for the development of new therapies. Recently, we demonstrated that ovarian CSCs survive cisplatin treatment through enhanced expression of DNA polymerase η (Pol η). Identification of micro RNA-93 (miR-93) as the regulator of Pol η provides a novel target to improve the outcome of platinum-based therapy. PMID:27308560

  4. A new class of flavonol-based anti-prostate cancer agents: Design, synthesis, and evaluation in cell models.

    Science.gov (United States)

    Li, Xiang; Chen, Guanglin; Zhang, Xiaojie; Zhang, Qiang; Zheng, Shilong; Wang, Guangdi; Chen, Qiao-Hong

    2016-09-01

    Flavonoids are a large class of polyphenolic compounds ubiquitously distributed in dietary plants with an array of biological activities. Flavonols are a major sub-class of flavonoids featuring a hydroxyl group at C-3. Certain natural flavonols, such as quercetin and fisetin, have been shown by in vitro cell-based and in vivo animal experiments to be potential anti-prostate cancer agents. However, the Achilles' heel of flavonols as drug candidates is their moderate potency and poor pharmacokinetic profiles. This study aims to explore the substitution effect of 3-OH in flavonols on the in vitro anti-proliferative potency against both androgen-sensitive and androgen-insensitive human prostate cancer cell lines. Our first lead flavonol (3',4'-dimethoxyflavonol), eight 3-O-alkyl-3',4'-dimethoxyflavonols, and six 3-O-aminoalkyl-3',4'-dimethoxyflavonols have been synthesized through aldol condensation and the Algar-Flynn-Oyamada (AFO) reaction. The WST-1 cell proliferation assay indicates (i) that all synthesized 3-O-alkyl-3',4'-dimethoxyflavonols and 3-O-aminoalkyl-3',4'-dimethoxyflavonols are more potent than the parent 3',4'-dimethoxyflavonol and the natural flavonol quercetin in suppressing prostate cancer cell proliferation; and (ii) that incorporation of a dibutylamino group to the 3-OH group through a three- to five-carbon linker leads to the optimal derivatives with up to 292-fold enhanced potency as compared with the parent flavonol. Flow cytometry analysis showed that the most potent derivative 22 can activate PC-3 cell cycle arrest at the G2/M phase and induce PC-3 cell apoptosis. No inhibitory ability of 22 up to 50μM concentration was observed against PWR-1E normal human epithelial prostate cells, suggesting its in vitro safety profile. The results indicate that chemical modulation at 3-OH is a vital strategy to optimize flavonols as anti-prostate cancer agents. PMID:27476422

  5. Serine Metabolism Supports the Methionine Cycle and DNA/RNA Methylation through De Novo ATP Synthesis in Cancer Cells

    OpenAIRE

    Maddocks, Oliver D. K.; Labuschagne, Christiaan F.; Adams, Peter D; Vousden, Karen H

    2016-01-01

    Summary: Crosstalk between cellular metabolism and the epigenome regulates epigenetic and metabolic homeostasis and normal cell behavior. Changes in cancer cell metabolism can directly impact epigenetic regulation and promote transformation. Here we analyzed the contribution of methionine and serine metabolism to methylation of DNA and RNA. Serine can contribute to this pathway by providing one-carbon units to regenerate methionine from homocysteine. While we observed this contribution under ...

  6. 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. PMID:27608951

  7. 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.

  8. Synthesis of [{sup 18}F]Xeloda as a novel potential PET radiotracer for imaging enzymes in cancers

    Energy Technology Data Exchange (ETDEWEB)

    Fei Xiangshu; Wang Jiquan; Miller, Kathy D.; Sledge, George W.; Hutchins, Gary D.; Zheng Qihuang E-mail: qzheng@iupui.edu

    2004-11-01

    Xeloda (Capecitabine), a prodrug of antitumor agent 5-fluorouracil, is the first and only oral fluoropyrimidine to be approved for use as second-line therapy in metastatic breast cancer, colorectal cancer, and other solid malignancies. Fluorine-18 labeled Xeloda may serve as a novel radiotracer for positron emission tomography (PET) to image enzymes such as thymidine phosphorylase and uridine phosphorylase in cancers. The precursor 2',3'-di-O-acetyl-5'-deoxy-5-nitro-N{sup 4}-(pentyloxycarbonyl)cytidine (11) was synthesized from D-ribose and cytosine in 8 steps with approximately 18% overall chemical yield. The reference standard 5'-deoxy-5-fluoro-N{sup 4}-(pentyloxycarbonyl)cytidine (Xeloda; 1) was synthesized from D-ribose and 5-fluorocytosine in eight steps with approximately 28% overall chemical yield. The target radiotracer 5'-deoxy-5-[{sup 18}F]fluoro-N{sup 4}-(pentyloxycarbonyl)cytidine ([{sup 18}F]Xeloda; [{sup 18}F]1) was prepared by nucleophilic substitution of the nitro-precursor with K{sup 18}F/Kryptofix 2.2.2 followed by a quick deprotection reaction and purification with the HPLC method in 20-30% radiochemical yields.

  9. Synthesis of [18F]Xeloda as a novel potential PET radiotracer for imaging enzymes in cancers

    International Nuclear Information System (INIS)

    Xeloda (Capecitabine), a prodrug of antitumor agent 5-fluorouracil, is the first and only oral fluoropyrimidine to be approved for use as second-line therapy in metastatic breast cancer, colorectal cancer, and other solid malignancies. Fluorine-18 labeled Xeloda may serve as a novel radiotracer for positron emission tomography (PET) to image enzymes such as thymidine phosphorylase and uridine phosphorylase in cancers. The precursor 2',3'-di-O-acetyl-5'-deoxy-5-nitro-N4-(pentyloxycarbonyl)cytidine (11) was synthesized from D-ribose and cytosine in 8 steps with approximately 18% overall chemical yield. The reference standard 5'-deoxy-5-fluoro-N4-(pentyloxycarbonyl)cytidine (Xeloda; 1) was synthesized from D-ribose and 5-fluorocytosine in eight steps with approximately 28% overall chemical yield. The target radiotracer 5'-deoxy-5-[18F]fluoro-N4-(pentyloxycarbonyl)cytidine ([18F]Xeloda; [18F]1) was prepared by nucleophilic substitution of the nitro-precursor with K18F/Kryptofix 2.2.2 followed by a quick deprotection reaction and purification with the HPLC method in 20-30% radiochemical yields

  10. Methods of 15N tracer research in biological systems

    International Nuclear Information System (INIS)

    The application of the stable isotope 15N is of increasing importance in different scientific disciplines, especially in medicine, agriculture, and the biosciences. The close correlation between the growing interest and improvements of analytical procedures resulted in remarkable advances in the 15N tracer technique. On the basis of the latest results of 15N tracer research in life sciences and agriculture methods of 15N tracer research in biological systems are compiled. The 15N methodology is considered under three headings: Chemical analysis with a description of methods of sample preparation (including different separation and isolation methods for N-containing substances of biological and agricultural origin) and special procedures converting ammonia to molecular nitrogen. Isotopic analysis with a review on the most important methods of isotopic analysis of nitrogen: mass spectrometry (including the GC-MS technique), emission spectrometry, NMR spectroscopy, and other analytical procedures. 15N-tracer techniques with a consideration of the role of the isotope dilution analysis as well as different labelling techniques and the mathematical interpretation of tracer data (modelling, N turnover experiments). In these chapters also sources of errors in chemical and isotopic analysis, the accuracy of the different methods and its importance on tracer experiments are discussed. Procedures for micro scale 15N analysis and aspects of 15N analysis on the level of natural abundance are considered. Furthermore some remarks on isotope effects in 15N tracer experiments are made. (author)

  11. The importance of serine metabolism in cancer.

    Science.gov (United States)

    Mattaini, Katherine R; Sullivan, Mark R; Vander Heiden, Matthew G

    2016-08-01

    Serine metabolism is frequently dysregulated in cancers; however, the benefit that this confers to tumors remains controversial. In many cases, extracellular serine alone is sufficient to support cancer cell proliferation, whereas some cancer cells increase serine synthesis from glucose and require de novo serine synthesis even in the presence of abundant extracellular serine. Recent studies cast new light on the role of serine metabolism in cancer, suggesting that active serine synthesis might be required to facilitate amino acid transport, nucleotide synthesis, folate metabolism, and redox homeostasis in a manner that impacts cancer. PMID:27458133

  12. 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.

  13. 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.

  14. 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.

  15. Reservoir sizing using inert and chemically reacting tracers

    Energy Technology Data Exchange (ETDEWEB)

    Robinson, B.A.; Tester, J.W.; Brown, L.F.

    1984-01-01

    Non-reactive tracer tests in prototype hot dry rock (HDR) geothermal reservoirs indicate multiple fracture flow paths that show increases in volume due to energy extraction. Tracer modal volumes correlate roughly with estimated reservoir heat-transfer capacity. Chemically reactive tracers are proposed which will map the rate of advance of the cooled region of an HDR reservoir, providing advanced warning of thermal drawdown. Critical parameters are examined using a simplified reservoir model for screening purposes. Hydrolysis reactions are a promising class of reactions for this purpose.

  16. Targeted Cancer Therapy Systems: An In Silico Study of Radiohalogenated Ligands in the Estrogen Receptor and the Synthesis of a Molecular Toolkit for the Fabrication of Customizable Nanoparticles

    Science.gov (United States)

    Barnsley, Kelton K.

    Chemotherapy is often limited by off-target toxicity and the development of multi-drug resistance in response to treatment. Strategies which reduce off-target toxicity by passively or actively targeting cancer cells may improve the efficacy of chemotherapy. Herein, two projects relating to targeted therapy are described. In the first project, the binding modes of 1,1-bis(4-hydroxyphenyl)-2-phenylethylenes (THPEs), a class of synthetic estrogens previously developed by our group, in the human estrogen receptor alpha-ligand binding domain were studied using molecular modeling programs YASARA AutoDock and Schrodinger Glide. The results were internally consistent and supported the observation that a bromine or iodine atom at the 2-position of the THPEs contributes positively to their binding in the estrogen receptor. In the second project, a "molecular toolkit" approach to the synthesis of multifunctional nanoparticles was envisioned. Our hypothesis was that the physical and chemical properties of the final product could be defined by controlling the types and relative amounts of prefunctionalized polymer units (PPUs) as well as the emulsification conditions. The design and syntheses of heterobifunctional linkers and other components for a preliminary molecular toolkit are reported, and the literature on select heterobifunctional aliphatic linkers is examined.

  17. National Biomedical Tracer Facility: Project definition study

    International Nuclear Information System (INIS)

    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

  18. Sedimentary radioactive tracers and diffusive models.

    Science.gov (United States)

    Carroll, J; Lerche, I

    2010-08-01

    This paper examines the underlying assumptions and consequences of applying a steady-state equation to sediment profiles of radioactive tracers in order to deconvolute sedimentation from bioturbation processes modelled as a diffusive type process. Several factors follow immediately from this investigation: (i) if the observed radioactive concentration increases with depth over any finite depth range then the proposed steady-state, constant flux equation is not applicable. Any increase in radioactive concentration with depth implies a negative mixing coefficient which is a physical impossibility; (ii) when the radioactive concentration systematically decreases with increasing sedimentary depth then solutions to the steady-state conservation equation exist only when either the constant solid state flux to the sediment surface is small enough so that a positive mixing coefficient results or when the mixing coefficient is small enough so that a positive flux results. If the radioactive concentration, porosity and/or density of the solid phase are such that the proposed equation is inappropriate (because no physically acceptable solution exists) then one must abandon the proposed steady-state equation. Further: if the flux of solid sediment to the sediment surface varies with time then, of course, a steady-state conservation equation is also inappropriate. Simple examples illustrate that the assumption of steady-state restricts the applicability of this modelling approach to a relatively small sub-set of expected situations in the real world.

  19. PAHs as a tracer of star formation?

    CERN Document Server

    Peeters, E; Tielens, A G G M

    2004-01-01

    IR emission bands at 3.3, 6.2, 7.7, 8.6 and 11.3 um are generally attributed to IR fluorescence from (mainly) FUV pumped PAHs. As such, they trace the FUV stellar flux and are a measure of star formation. We examined the IR spectral characteristics of Galactic star forming regions, normal and starburst galaxies, AGNs and ULIRGs. The goal is to analyze if PAH bands are a good qualitative and/or quantitative tracer of star formation and hence the application of PAH bands as a diagnostic in order to identify the dominant processes contributing to the IR emission from Seyfert's and ULIRGs. We develop a MIR/FIR diagnostic and compare it to known diagnostics, with these also applied to the Galactic sample. This diagnostic is based on the FIR normalized 6.2 um PAH flux and the FIR normalized 6.2 um continuum flux. The Galactic sources form a sequence spanning a range of 3 orders of magnitude, from embedded compact HII regions to exposed PDRs and the (D)ISM. The variation in the 6.2 um PAH/continuum ratio is relative...

  20. Positron emitting tracers for studies of cocaine

    International Nuclear Information System (INIS)

    The use of PET to study the behavior and mechanism of action of therapeutic drugs and substances of abuse can be approached from a number of perspectives. The most common approach is to measure the effect of a drug on some aspect of metabolism and requires well characterized radiotracers whose behavior in vivo can be related to a discrete biochemical transformation. A second approach is to study the labeled drug itself. This provides information on the drug's regional distribution and kinetics as well as its pharmacological profile and metabolism. Cocaine has been labeled in different positions with carbon-11 and with fluorine-18 and the stereoisomers of cocaine have also been labeled to characterize its binding and metabolism in human and baboon brain. Regional cocaine binding as measured by PET is consistent with reversible binding to striatal dopamine reuptake sites and its time course parallels the behavioral activation of cocaine. The behaviorally inactive enantiomer (+)-cocaine is rapidly metabolized in serum preventing its entry into the brain. These PET tracers are useful in understanding the neurochemical basis of cocaine's action

  1. 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.

  2. 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.

  3. Design, synthesis, and evaluation of chitosan conjugated GGRGDSK peptides as a cancer cell-targeting molecular transporter.

    Science.gov (United States)

    El-Sayed, Naglaa S; Shirazi, Amir N; El-Meligy, Magda G; El-Ziaty, Ahmed K; Nagieb, Zenat A; Parang, Keykavous; Tiwari, Rakesh K

    2016-06-01

    Targeting cancer cells using integrin receptor is one of the promising targeting strategies in drug delivery. In this study, we conjugated an integrin-binding ligand (GGRGDSK) peptide to chitosan oligosaccharide (COS) using sulfo-SMCC as a bifunctional linker to afford COS-SMCC-GGRGDSK. The conjugated polymer was characterized by FT-IR, (1)H NMR, (13)C NMR, and SEM. COS-SMCC-GGRGDSK did not show cytotoxicity up to a concentration of 1mg/mL in the human leukemia cell line (CCRF-CEM). The conjugate was evaluated for its ability to enhance the cellular uptake of a cell-impermeable cargo (e.g., F'-G(pY)EEI phosphopeptide) in CCRF-CEM, and human ovarian carcinoma (SK-OV-3) cancer cell lines. Additionally, RGD modified and unmodified COS polymers were used to prepare nanoparticles by ionic gelation and showed particle size ranging from 187 to 338nm, and zeta potential of 12.2-18.3mV using dynamic light scattering. The efficiency of COS-NPs and COS-SMCC-RGDSK NPs was assayed for translocation of two synthetic cytotoxic agents ((2-(2-aminoethylamino)-4-(4-chlorophenyl)-6-(1H-indol-3-yl) nicotinonitrile (ACIN), and 2-(2-aminoethylamino)-6-(1H-indol-3-yl)-4-(4-methoxyphenyl)-nicotinonitrile (AMIN)) into CCRF-CEM and human prostate (DU-145) cancer cell lines. The results showed a dramatic reduction in the cell viability on their treatment with RGD targeted COS NPs in comparison to paclitaxel (PTX), free drug, and drug-loaded COS NPs. PMID:26976071

  4. 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

  5. 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.

  6. 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.

  7. Cancer Basics

    Science.gov (United States)

    ... Cancer? Breast Cancer Colon/Rectum Cancer Lung Cancer Prostate Cancer Skin Cancer Show All Cancer Types News and Features Cancer Glossary ACS Bookstore Cancer Information Cancer Basics Cancer Prevention & Detection Signs & Symptoms of Cancer Treatments & Side Effects ...

  8. 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.

  9. 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.

  10. 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.

  11. Synthesis, characterization and in vitro anti-cancer evaluation of hesperetin-loaded nanoparticles in human oral carcinoma (KB) cells

    International Nuclear Information System (INIS)

    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. (paper)

  12. Applications of isotopic tracer in analysis of residual sulfonylurea herbicide

    International Nuclear Information System (INIS)

    The analysis technique of the agrochemical residue by isotopic tracer is significantly increased, and obtained substantial development. The progress of the isotopic analysis in four kinds of sulfonylurea herbicide residues was reviewed in this paper. (authors)

  13. Application of fluorescent-and radioactive tracers in Sedimentalogy

    International Nuclear Information System (INIS)

    The development of techniques of sediment labelling, creating the possibility of using fluorescent and radioactive tracers not yet applied in Brazil, in the area of sedimentology, is studied. (A.R.H.)

  14. 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.

  15. Our experience of blood flow measurements using radioactive tracers

    International Nuclear Information System (INIS)

    A critical study of blood flow measuring methods is proposed. After a review of the various diffusible and non-diffusible radioactive tracers and the corresponding detector systems, the principles which allow to measure blood flow from the data so obtained, are studied. There is a different principle of flow measurement for each type of tracer. The theory of flow measurement using non-diffusible tracers (human serum albumin labelled with 131I or sup(99m)Tc, 113In-labelled siderophiline) and its application to cardiac flow measurement are described first. Then the theory of flow measurement using diffusible tracers (133Xe, 85Kr) and its application to measurement of blood flow through tissues (muscles and kidney particularly) are described. A personal experience of this various flow measurements is reported. The results obtained, the difficulties encountered and the improvments proposed are developed

  16. Systems approach to tracer data in groundwater hydrology

    International Nuclear Information System (INIS)

    A brief review of current mathematical methods for the analysis of tracer data in groundwater hydrology has been given. The description of the hydrological cycle as a whole or in part, by a system (compartment) or sub-system under linear and stationary conditions is discussed. Basic concepts of transit time, residence time, their distributions in time and response characteristics of a system are outlined. From the knowledge of tracer input, output and systems response function for a generalised system, reservoir capacity and storage for given period can be estimated. Use of a time series model for environmental tracer data in discreet time scale aimed at the solution of hydrological problems e.g. mean transit time and reservoir capacity is also explored. It is concluded that the combination of tracer data with systems approach can go a long way in the study of some complex hydrological problems. (author)

  17. 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.

  18. Self-diffusion of ion-implanted tracers

    International Nuclear Information System (INIS)

    Tracer self-diffusion studies with ion-implanted stable isotopes require a high fluence of implanted ions (>1015 ions/cm2) due to the natural tracer background concentration present in a sample. Such a high fluence leads to considerable implantation damage, where a large part of the tracer is immobilized and does not take place in the diffusion process. As a consequence, diffusion profiles are observed which cannot be described with Fick's second law. In this study, a set of differential equations is presented, describing the diffusion of implanted isotopes as a trap-limited process with a sink and a source term, where the tracer atoms form immobile complexes with implantation damage-induced defects. These equations are solved numerically for the example of nitrogen diffusion in amorphous Si-B-C-N ceramics in order to illustrate diffusivity determination. The results are compared to the analytical solution of Fick's second law

  19. 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.

  20. Monodisperse magnetite nanoparticle tracers for in vivo magnetic particle imaging

    OpenAIRE

    Khandhar, Amit P.; Ferguson, R. Matthew; Arami, Hamed; Krishnan, Kannan M

    2013-01-01

    Magnetic Particle Imaging (MPI) is a new biomedical imaging modality that produces real-time, high-resolution tomographic images of superparamagnetic iron oxide (SPIO) nanoparticle tracer distributions. In this study, we synthesized monodisperse tracers for enhanced MPI performance and investigated both, their blood clearance time using a 25 kHz magnetic particle spectrometer (MPS), and biodistribution using a combination of quantitative T2-weighted MRI and tissue histology. In vitro and in v...

  1. Clustering of dark matter tracers: renormalizing the bias parameters

    OpenAIRE

    McDonald, Patrick

    2006-01-01

    A commonly used perturbative method for computing large-scale clustering of tracers of mass density, like galaxies, is to model the tracer density field as a Taylor series in the local smoothed mass density fluctuations, possibly adding a stochastic component. I suggest a set of parameter redefinitions, eliminating problematic perturbative correction terms, that should represent a modest improvement, at least, to this method. As presented here, my method can be used to compute the power spect...

  2. Key aspects of stratospheric tracer modeling using assimilated winds

    OpenAIRE

    Bregman, B.; E. Meijer; R. Scheele

    2006-01-01

    International audience; This study describes key aspects of global chemistry-transport models and their impact on stratospheric tracer transport. We concentrate on global models that use assimilated winds from numerical weather predictions, but the results also apply to tracer transport in general circulation models. We examined grid resolution, numerical diffusion, air parcel dispersion, the wind or mass flux update frequency, and time interpolation. The evaluation is performed with assimila...

  3. Tracer populations in the Local Group

    Science.gov (United States)

    Watkins, Laura L.

    2011-04-01

    So often in astronomy, an object is not considered for its individual merits, but for what we may learn from its properties regarding some larger population. The existence of dark matter is a prime example of this; we cannot see it directly but we can infer its presence by noting its effects on the stars orbiting within its potential. This thesis describes how various sets of tracer populations can be used to probe the properties of a variety of galaxies in the Local Group. I begin by describing the extraction of a variable catalogue from the Sloan Digital Sky Survey Stripe 82 dataset and then use the catalogue to select a high-quality set of RR Lyrae stars. Analysing the distribution of the RR Lyraes reveals three significant substructures in the Milky Way halo: the Hercules-Aquila Cloud and the Sagittarius Stream, which were already known to exist, and the Pisces Overdensity, which was previously undetected. It is a faint, extended structure found at ~80 kpc and is of unknown origin. Altogether, I find that nearly 80% of the RR Lyraes are associated with substructures, consistent with the theory that galaxy halos are predominantly, or even entirely, made up from disrupted satellites. I also investigate the density distribution of RR Lyraes in the halo, finding that it is best fit by a broken-power-law model, in good agreement with previous work. I go on to develop a set of tracer mass estimators that build on previous work which make use of actual (and not projected) distance and proper motion data, reflecting the amount and quality of data now available to us. I show that proper motion data is, in theory, very useful and can greatly increase the accuracy of the mass estimates; in practice, however, current analysis is hampered by the large errors inherent in the proper motion data. The results are also subject to mass-anisotropy degeneracy, which current data is not yet able to break. Nevertheless, I am able to estimate the mass of the Milky Way to be M = 2.7±0

  4. 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 ...

  5. Determination of the self purification of streams using tracers

    International Nuclear Information System (INIS)

    A methodology for the 'in situ' evaluation of the self purification of streams is discussed. It consists of the simultaneous injection of two tracers into the stream. One of the tracers is oxidized by biochemical processes. It can be either artificially supplied to the stream or a naturally present component can be used. This tracer is used for the determination of the self purification parameters. The other tracer is conservative and allows for the hydrodynamic effects. Tests have been carried out in two streams with quite different hydrodynamic and physicochemical conditions. In the first stream, with a flow-rate of about 0.9 m3/s, urea was used as the nonconservative tracer. In the other stream, which had a flow-rate of about 5 m3/s, only a radioactive tracer has been used, and the rate of biochemical oxidation has been determined from BOD measurements. Calculations have been implemented on a digital computer. In both cases it was found that the reoxygenation rate is more conveniently determined by empirical formulas. Results from both tests have been deemed realistic by comparison with similar experiments. (Author)

  6. Evaluation of four blood pump geometries: the optical tracer technique.

    Science.gov (United States)

    Rose, M L; Mackay, T G; Martin, W; Wheatley, D J

    2000-01-01

    Artificial blood pump assistance of the failing human heart can allow it to recover. Analysis of blood pump fluid flow is a useful tool for design development and thrombosis minimization. The aim of this study was to investigate fluid flow, particularly ventricular clearance rate and stagnation areas, in four different blood pump geometries and to determine the best design. The blood pumps consisted of a polyurethane ventricle, and combinations of inlet/outlet pipe angles and compression plate shapes. A video camera recorded the motion of fluid labelled with an optical tracer (Methyl Blue histological dye). A novel processing method was developed to produce colour maps of tracer concentration, experimentally calibrated. An overall picture of fluid flow in each pump geometry was generated by considering clearance curves, tracer concentration maps and inflow jet animations. Overall and local mixing coefficients are calculated for each pump. The best geometry featured straight inlet/outlet pipes and a domed compression plate. This optical tracer technique has proven convenient, economical, sensitive to low concentrations of tracer and provides instantaneous pictures of tracer distribution in a ventricle. PMID:10997058

  7. 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.

  8. Synthesis and biological evaluation of novel folic acid receptor-targeted, β-cyclodextrin-based drug complexes for cancer treatment.

    Directory of Open Access Journals (Sweden)

    Juan-Juan Yin

    Full Text Available Drug targeting is an active area of research and nano-scaled drug delivery systems hold tremendous potential for the treatment of neoplasms. In this study, a novel cyclodextrin (CD-based nanoparticle drug delivery system has been assembled and characterized for the therapy of folate receptor-positive [FR(+] cancer. Water-soluble folic acid (FA-conjugated CD carriers (FACDs were successfully synthesized and their structures were confirmed by 1D/2D nuclear magnetic resonance (NMR, matrix-assisted laser desorption ionization time-of-flight mass spectrometer (MALDI-TOF-MS, high performance liquid chromatography (HPLC, Fourier transform infrared spectroscopy (FTIR, and circular dichroism. Drug complexes of adamatane (Ada and cytotoxic doxorubicin (Dox with FACD were readily obtained by mixed solvent precipitation. The average size of FACD-Ada-Dox was 1.5-2.5 nm. The host-guest association constant K a was 1,639 M(-1 as determined by induced circular dichroism and the hydrophilicity of the FACDs was greatly enhanced compared to unmodified CD. Cellular uptake and FR binding competitive experiments demonstrated an efficient and preferentially targeted delivery of Dox into FR-positive tumor cells and a sustained drug release profile was seen in vitro. The delivery of Dox into FR(+ cancer cells via endocytosis was observed by confocal microscopy and drug uptake of the targeted nanoparticles was 8-fold greater than that of non-targeted drug complexes. Our docking results suggest that FA, FACD and FACD-Ada-Dox could bind human hedgehog interacting protein that contains a FR domain. Mouse cardiomyocytes as well as fibroblast treated with FACD-Ada-Dox had significantly lower levels of reactive oxygen species, with increased content of glutathione and glutathione peroxidase activity, indicating a reduced potential for Dox-induced cardiotoxicity. These results indicate that the targeted drug complex possesses high drug association and sustained drug release

  9. Marine chemistry and tracer applications of radiocaesium

    International Nuclear Information System (INIS)

    The general aims of this project were to study the marine chemistry of Windscale-derived radiocaesium and to continue previous research at Glasgow University on its tracer application in Scottish waters and sediments. It was found that a considerable percentage of sediment-associated 137Cs (approximately 12 to 50%) may be contained by carbonate, oxide and organic coatings which appear to be relatively stable under a wide range of redox conditions. Whilst the partitioning of 137Cs is related to the concentration of these oxides, organics and, to a much lesser extent, carbonates, their function is predominantly to prevent 137Cs release from clay mineral exchange sites. 137Cs activities per unit sediment weight were highest in the clay fraction with its uptake by coarse sediments appearing to be controlled by clay minerals coatings formed in the marine environment and cemented partly by oxides and organics. Though the sites sampled (Clyde Sea Area (C.S.A.) and L. Etive) encompassed a wide range of sediment types, the range of estimated 137Cs distribution coefficients (KD) was relatively small (360 to 890). Coatings may thus have more influence on Kds in the coastal marine environment than particle size distributions. Apparent concentration factors (CFs) of X325, X2800 and X1910 were determined for the associated carbonate, oxide and organic coatings, for a site off Greenock. Use of 'dry' sediments appeared to produce considerably overestimated values for the degree of 137Cs fixation. Thus 'wet' sediments were used in these studies. Over the 1978-1981 period, approximately 35% of Windscale output passed through the C.S.A., diluted 26 times during transit. An estimated 0.3% of this water-borne inventory was removed into the sediments. Windscale to C.S.A. transit and residence times of 4 and 12 months respectively were derived. Monitoring the deeper levels of L. Etive allowed 137Cs to be used to trace patterns of w

  10. Nickel isotopes as a new geochemical tracer

    Science.gov (United States)

    Gall, L.; Williams, H. M.; Siebert, C.; Halliday, A.

    2010-12-01

    Research into "non-traditional" stable isotope systems has been of great interest over the past decade. The stable isotope system of nickel (Ni) has not been studied as intensively as other transition metals (e.g. Fe, Cr, Cu, Zn, and Mo), even though it is a ubiquitous element in geological environments and is a bioessential trace metal, e.g. for production of methane by methanogens. We have developed a novel chemical separation procedure to isolate Ni from most geological matrices. Because of its chemical behavior during ion-exchange chromatography complete separation of Ni is very complex. We therefore make use of a Ni double spike that allows us to optimize the chemical separation and correct instrumental mass bias during mass spectrometry analysis. This technique allows high precision Ni isotope measurements resulting in long term external reproducibility of USGS rock standard BHVO-2 of 0.09‰ (2s.d.) on δ60/58Ni with typical measurement errors as low as 0.04‰ (2s.d.). We have measured the isotope composition of Ni in a variety of terrestrial samples demonstrating significant isotope variation. In magmatic rocks Ni isotopes appear to be largely homogeneous, with only small variations (no more than 0.2‰) between different rock types, from ultramafic to felsic. There is no evidence of significant isotopic fractionation during melting and differentiation of the silicate Earth. In contrast we find significant systematic isotope variations (up to 1.5‰) between magmatic rocks and FeMn crusts, shales and sulphides. Our data clearly demonstrate mass-dependent fractionation of Ni isotopes in the marine and terrestrial environment by inorganic processes, in addition to the biological fractionations already reported by others, highlighting the potential of Ni isotopes as a powerful new tracer for Earth Surface processes.

  11. 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. PMID:27251153

  12. 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...

  13. Quantification of lung cancer risk after low radon exposure and low exposure rate: synthesis from epidemiological and experimental data

    International Nuclear Information System (INIS)

    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)

  14. 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)

  15. 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

    2015-03-01

    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. PMID:25590864

  16. Synthesis and evaluation of naphthalene-based thiosemicarbazone derivatives as new anticancer agents against LNCaP prostate cancer cells.

    Science.gov (United States)

    Altintop, Mehlika Dilek; Sever, Belgin; Özdemir, Ahmet; Kuş, Gökhan; Oztopcu-Vatan, Pinar; Kabadere, Selda; Kaplancikli, Zafer Asim

    2016-06-01

    Fourteen new naphthalene-based thiosemicarbazone derivatives were designed as anticancer agents against LNCaP human prostate cancer cells and synthesized. MTT assay indicated that compounds 6, 8 and 11 exhibited inhibitory effect on LNCaP cells. Among these compounds, 4-(naphthalen-1-yl)-1-[1-(4-hydroxyphenyl)ethylidene)thiosemicarbazide (6), which caused more than 50% death on LNCaP cells, was chosen for flow cytometric analysis of apoptosis. Flow cytometric analysis pointed out that compound 6 also showed apoptotic effect on LNCaP cells. Compound 6 can be considered as a promising anticancer agent against LNCaP cells owing to its potent cytotoxic activity and apoptotic effect. PMID:25826149

  17. HYDROGEL TRACER BEADS: THE DEVELOPMENT, MODIFICATION, AND TESTING OF AN INNOVATIVE TRACER FOR BETTER UNDERSTANDING LNAPL TRANSPORT IN KARST AQUIFERS

    Energy Technology Data Exchange (ETDEWEB)

    Amanda Laskoskie, Harry M. Edenborn, and Dorothy J. Vesper

    2012-01-01

    The goal of this specific research task is to develop proxy tracers that mimic contaminant movement to better understand and predict contaminant fate and transport in karst aquifers. Hydrogel tracer beads are transported as a separate phase than water and can used as a proxy tracer to mimic the transport of non-aqueous phase liquids (NAPL). They can be constructed with different densities, sizes & chemical attributes. This poster describes the creation and optimization of the beads and the field testing of buoyant beads, including sampling, tracer analysis, and quantitative analysis. The buoyant beads are transported ahead of the dissolved solutes, suggesting that light NAPL (LNAPL) transport in karst may occur faster than predicted from traditional tracing techniques. The hydrogel beads were successful in illustrating this enhanced transport.

  18. 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.

  19. New testosterone derivatives as semi-synthetic anticancer agents against prostate cancer: synthesis and preliminary biological evaluation.

    Science.gov (United States)

    Morin, Nathalie; Bruneau, Julie; Fortin, Sebastien; Brasseur, Kevin; Leblanc, Valerie; Asselin, Eric; Berube, Gervais

    2015-01-01

    Prostate cancer (PC) is a major health issue in the world. Treatments of localized PC are quite efficient and usually involve surgery, radiotherapy and/or hormonal therapy. Metastatic PC is however rarely curable to this day. Treatments of metastatic PC involve radiotherapy, chemotherapy and hormonal treatment such as orchiectomy, antiandrogens and luteinizing hormone-releasing hormone agonists. The suppression of tumor growth by hormonal treatment is efficient but overtime resistance still occurs and the disease progresses. Thus, more urgently than ever there is a need for discovery of new treatment options for castration-resistant PC (CRPC). Hence, we designed and tested a series of amide derivatives located at position 7α of testosterone as prospective "natural" or "semisynthetic" anticancer agents against CRPC with the goal of discovering therapeutic alternatives for the disease. This manuscript describes an efficient path towards the target molecules that are made in only 6 or 7 chemical steps from testosterone in good overall yields. This strategy can be used to make several compounds of interest that present higher biological activity than the classic antiandrogen; cyproterone acetate (3). The best testosterone-7α-amide was the N-2-pyridylethylamide (25) which was as active as the antiandrogen cyproterone acetate (3) on androgen-dependent LNCaP cells and 2.7 times more active on androgen-independent PC3 prostate cancer cells. The results obtained show the synthetic feasibility and the potential for future development of this unique class of semi-synthetic anticancer agents that offer the premise of new treatment modalities for patients afflicted with CRPC. PMID:25675439

  20. 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. PMID:21709916

  1. Field tracer experiments: Role in the prediction of radionuclide migration. [Proceedings

    International Nuclear Information System (INIS)

    GEOTRAP is an OECD/NED Project devoted to radionuclide migration in geologic, heterogeneous media in the framework of site evaluation and safety assessment of deep repository systems for high-level and/or long-lived radioactive waste. The first GEOTRAP workshop, Field Tracer Experiments: Role in the Prediction of Radionuclide Migration (Cologne, Germany, 28--30 August 1996) was co-organized with the European Commission. It gave an overview of on-going and planned work in the study of radionuclide transport phenomena and the characterization of relevant properties of the geologic media. In addition to the papers presented at the workshop, these proceedings include a synthesis of the materials presented, the discussions that took place and the conclusions drawn, notably during working group sessions

  2. On the time to tracer equilibrium in the global ocean

    Directory of Open Access Journals (Sweden)

    F. Primeau

    2009-02-01

    Full Text Available An important issue for the interpretation of data from deep-sea cores is the time for tracers to be transported from the sea surface to the deep ocean. Global ocean circulation models can help shed light on the timescales over which a tracer comes to equilibrium in different regions of the ocean. In this note, we discuss how the most slowly decaying eigenmode of a model can be used to obtain a relevant timescale for a tracer that enters through the sea surface to become well mixed in the ocean interior. We show how this timescale depends critically on the choice between a Neumann surface boundary condition in which the flux of tracer is prescribed, a Robin surface boundary condition in which a combination of the flux and tracer concentration is prescribed or a Dirichlet surface boundary condition in which the concentration is prescribed. Explicit calculations with a 3-box model and a three-dimensional ocean circulation model show that the Dirichlet boundary condition when applied to only part of the surface ocean greatly overestimate the time needed to reach equilibrium. As a result regional-"injection" calculations which prescribe the surface concentration instead of the surface flux are not relevant for interpreting the regional disequilibrium between the Atlantic and Pacific found in paleo-tracer records from deep-sea cores. For tracers that enter the ocean through air-sea gas exchange a prescribed concentration boundary condition can be used to infer relevant timescales if the air-sea gas exchange rate is sufficiently fast, but the boundary condition must be applied over the entire ocean surface and not only to a patch of limited area. For tracers with a slow air-sea exchange rate such as 14C a Robin-type boundary condition is more relevant and for tracers such as δ18O that enter the ocean from melt water, a Neumann boundary condition is presumably more relevant. Our three-dimensional model results based on a steady

  3. 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

  4. 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

  5. Heat tracer test in an alluvial aquifer: field experiment and inverse modelling

    OpenAIRE

    Klepikova, Maria; Wildemeersch, Samuel; Jamin, Pierre; Orban, Philippe; Hermans, Thomas; Nguyen, Frédéric; Brouyère, Serge; Dassargues, Alain

    2016-01-01

    Using heat as an active tracer for aquifer characterization is a topic of increasing interest. In this study, we investigate the potential of using heat tracer tests for characterization of a shallow alluvial aquifer. A thermal tracer test was conducted in the alluvial aquifer of the Meuse River, Belgium. The tracing experiment consisted in simultaneously injecting heated water and a dye tracer in a piezometer and monitoring the evolution of groundwater temperature and tracer concentration in...

  6. Heat tracer and solute tests in an alluvial aquifer: field experiment and inverse modelling

    OpenAIRE

    Dassargues, Alain; Klepikova, Maria; Jamin, Pierre; Orban, Philippe; Brouyère, Serge

    2015-01-01

    Using heat as an active tracer in different types of aquifers is a topic of increasing interest. In this study, we investigate the potential interest of using heat tracer tests for characterization of a shallow alluvial aquifer. A thermal tracer test was conducted in the alluvial aquifer of the Meuse River, Belgium. The tracing experiment consisted in simultaneously injecting heated water and a dye tracer in a piezometer and monitoring the evolution of groundwater temperature and tracer conce...

  7. 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

  8. 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

  9. 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

  10. A new PET tracer producing facility

    International Nuclear Information System (INIS)

    constructing a building, that will receive a new dedicate cyclotron, as well as the radiopharmacy laboratories. The mediate objective is supplying the regional demand of positron emitters, and offer last generation diagnosis. The starting labeled molecule is 18FDG. By the end of 2004, the level of production will be around 5 Ci/week of 18FDG, enough to fulfill the hospital's needs inside our state. The specific objective is the setting up of a PET tracer producing facility. As a mediate result we will have a reduction in costs and expenses with therapies. A final and sustained result will be a positive impact on the public health system and on the region's quality of life

  11. 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.

  12. Transport of Passive Tracers in Baroclinic Wave Life Cycles

    Science.gov (United States)

    Stone, Elizabeth M.; Randel, William J.; Stanford, John L.

    1999-01-01

    The transport of passive tracers in idealized baroclinic wave life cycles is studied using output from the National Center for Atmospheric Research Community Climate Model (CCM2). Two life cycles, LCn and LCs, are simulated, starting with baroclinically unstable initial conditions similar to those used by Thorncroft et al. in their study of two life cycle paradigms. The two life cycles LCn and LCs have different initial horizontal wind shear structures that result in distinctive nonlinear development. In terms of potential vorticity-potential temperature (PV-theta) diagnostics, the LCn case is characterized by thinning troughs that are advected anti-cyclonically and equatorward, while the LCs case has broadening troughs that wrap up cyclonically and poleward. Four idealized passive tracers are included in the model to be advected by the semi-Lagrangian transport scheme of the CCM2, and their evolutions are investigated throughout the life cycles. Tracer budgets are analyzed in terms of the transformed Eulerian mean constituent transport formalism in pressure coordinates and also in isentropic coordinates. Results for both LCn and LCs show transport that is downgradient with respect to the background structure of the tracer field, but with a characteristic spatial structure that maximizes in the middle to high latitudes. For the idealized tropospheric tracers in this study, this represents a net upward and poleward transport that enhances concentrations at high latitudes. These results vary little with the initial distribution of the constituent field. The time tendency of the tracer is influenced most strongly by the eddy flux term. with the largest transport occurring during the nonlinear growth stage of the life cycle. The authors also study the transport of a lower-stratospheric tracer, to examine stratosphere-troposphere exchange for baroclinic waves.

  13. 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.

  14. 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

  15. 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

  16. Nitric oxide synthesis inhibition and cytotoxicity of Korean horse mussel Modiolus modiolus extracts on cancer cells in culture.

    Science.gov (United States)

    Wikarta, Jumeri Mangun; Kim, Sang Moo

    2016-08-01

    The Korean horse mussel extract was purified and fractionated by a bioassay-guided purification step. The final fraction contained seven steroid and one polycyclic aromatic compounds, in which cholest-7-en-3-ol, (3β,5α)- (58.7 %) was a main component followed by ergosta-7,22dien-3-ol (3β,5α,22E) (13.0 %). This extract exhibited strong anti-inflammatory activity determined solely through the nitric oxide inhibition assay in a dose-dependant manner with the IC50 value of 9.6 µg/mL and no cytotoxic effect on the macrophages. Moreover, it also exhibited strong cytotoxicity with the IC50 values of 21.4, 36.4, and 37.1 µg/mL against AGS, DLD-1, and HeLa cells, respectively. These results indicated that the horse mussel extract might be a functional ingredient in the prevention of inflammation and human cancers. PMID:25875500

  17. 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.

  18. Synthesis and evaluation of thymidine kinase 1-targeting carboranyl pyrimidine nucleoside analogs for boron neutron capture therapy of cancer.

    Science.gov (United States)

    Agarwal, Hitesh K; Khalil, Ahmed; Ishita, Keisuke; Yang, Weilian; Nakkula, Robin J; Wu, Lai-Chu; Ali, Tehane; Tiwari, Rohit; Byun, Youngjoo; Barth, Rolf F; Tjarks, Werner

    2015-07-15

    A library of sixteen 2nd generation amino- and amido-substituted carboranyl pyrimidine nucleoside analogs, designed as substrates and inhibitors of thymidine kinase 1 (TK1) for potential use in boron neutron capture therapy (BNCT) of cancer, was synthesized and evaluated in enzyme kinetic-, enzyme inhibition-, metabolomic-, and biodistribution studies. One of these 2nd generation carboranyl pyrimidine nucleoside analogs (YB18A [3]), having an amino group directly attached to a meta-carborane cage tethered via ethylene spacer to the 3-position of thymidine, was approximately 3-4 times superior as a substrate and inhibitor of hTK1 than N5-2OH (2), a 1st generation carboranyl pyrimidine nucleoside analog. Both 2 and 3 appeared to be 5'-monophosphorylated in TK1(+) RG2 cells, both in vitro and in vivo. Biodistribution studies in rats bearing intracerebral RG2 glioma resulted in selective tumor uptake of 3 with an intratumoral concentration that was approximately 4 times higher than that of 2. The obtained results significantly advance the understanding of the binding interactions between TK1 and carboranyl pyrimidine nucleoside analogs and will profoundly impact future design strategies for these agents. PMID:26087030

  19. Design, synthesis, and biological evaluation of resveratrol analogues as aromatase and quinone reductase 2 inhibitors for chemoprevention of cancer

    International Nuclear Information System (INIS)

    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 (IC50 0.59 μM) 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 (IC50 70 nM) and 84 (IC50 36 nM). The aromatase inhibitory activities of these compounds are much more potent than that for the lead compound resveratrol, which has an IC50 of 80 μM. In addition to aromatase inhibitory activity, compounds 32 and 44 also displayed potent QR2 inhibitory activity (IC50 1.7 μM and 0.27 μM, 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.

  20. 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.

  1. Advances in processes for PET radiotracer synthesis: Separation of [18F]fluoride from enriched [18O]water

    International Nuclear Information System (INIS)

    Positron emission tomography (PET) is a powerful scientific and clinical tool for the study and visualization of human physiology that can provide important information about metabolism and diseases such as cancer. At present, [18F]fluorodeoxyglucose ([18F]FDG) is the most frequently used radiotracer for the routine clinical evaluation of malignant tumors in a range of body tissues. FDG synthesis is continuously being developed to improve and simplify the synthetic procedure including the isolation of [18F]fluoride from [18O]water. There are many methods reported in literature for the isolation of [18F]fluoride, including evaporation, coat-capture–elution, the use of cation-exchange resin and electrode trapping. This review article gives an overview of some of the most common methods for the separation of [18F]fluoride ions from [18O]water, highlighting the potential strength of the methods and also problems and weaknesses for synthesis of 18F PET tracers. - Highlights: • New developments in processing of [18F]fluoride from [18O]water are detailed. • Efficient separation is required for dose-on-demand radiopharmaceuticals. • Electrode trapping of [18F]fluoride offers significant advantages for solvent exchange. • Microfluidic devices complement novel technologies for isotope separation and synthesis

  2. Fully-automated synthesis of 16β-18F-fluoro-5α-dihydrotestosterone (FDHT) on the ELIXYS radiosynthesizer

    International Nuclear Information System (INIS)

    Noninvasive in vivo imaging of androgen receptor (AR) levels with positron emission tomography (PET) is becoming the primary tool in prostate cancer detection and staging. Of the potential 18F-labeled PET tracers, 18F-FDHT has clinically shown to be of highest diagnostic value. We demonstrate the first automated synthesis of 18F-FDHT by adapting the conventional manual synthesis onto the fully-automated ELIXYS radiosynthesizer. Clinically-relevant amounts of 18F-FDHT were synthesized on ELIXYS in 90 min with decay-corrected radiochemical yield of 29±5% (n=7). The specific activity was 4.6 Ci/µmol (170 GBq/µmol) at end of formulation with a starting activity of 1.0 Ci (37 GBq). The formulated 18F-FDHT yielded sufficient activity for multiple patient doses and passed all quality control tests required for routine clinical use. - Highlights: • Manual radiosynthesis of 18F-FDHT was adapted for full automation on the ELIXYS radiosynthesizer. • Reduction with LiAlH4 was performed at room temperature to avoid cryogenic conditions. • Formulated product passed all clinical QC tests and is suitable for clinical production. • Decay-corrected radiochemical yield was 29±5% (n=7) with a synthesis time of 90 min. • Specific activity was 4.6 Ci/µmol (170 GBq/µmol) at the end of formulation

  3. 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

  4. Partitioning Gas Tracer Technology for Measuring Water in Landfills

    Science.gov (United States)

    Briening, M. L.; Jakubowitch, A.; Imhoff, P. T.; Chiu, P. C.; Tittlebaum, M. E.

    2002-12-01

    Unstable landfills can result in significant environmental contamination and can become a risk to public health. To reduce this risk, water may be added to landfills to ensure that enough moisture exists for biodegradation of organic wastes. In this case risks associated with future breaks in the landfill cap are significantly reduced because organic material is degraded more rapidly. To modify moisture conditions and enhance biodegradation, leachate is typically collected from the bottom of the landfill and then recirculated near the top. It is difficult, though, to know how much leachate to add and where to add it to achieve uniform moisture conditions. This situation is exacerbated by the heterogeneous nature of landfill materials, which is known to cause short circuiting of infiltrating water, a process that has been virtually impossible to measure or model. Accurate methods for measuring the amount of water in landfills would be valuable aids for implementing leachate recirculation systems. Current methods for measuring water are inadequate, though, since they provide point measurements and are frequently affected by heterogeneity of the solid waste composition and solid waste compaction. The value of point measurements is significantly reduced in systems where water flows preferentially, such as in landfills. Here, spatially integrated measurements might be of greater value. In this research we are evaluating a promising technology, the partitioning gas tracer test, to measure the water saturation within landfills, the amount of free water in solid waste divided by the volume of the voids. The partitioning gas tracer test was recently developed by researchers working in the vadose zone. In this methodology two gas tracers are injected into a landfill. One tracer is non-reactive with landfill materials, while the second partitions into and out of free water trapped within the pore space of the solid waste. Chromatographic separation of the tracers occurs

  5. 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.

  6. Development of radioisotope tracer technology and nucleonic control system

    International Nuclear Information System (INIS)

    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)

  7. 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)

  8. 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.

  9. 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 manufacturing methods can be achieved in the academic setting and need to be considered for critical components of future metabolic studies.

  10. 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...

  11. 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 manufacturing methods can be achieved in the academic setting and need to be considered for critical components of future metabolic studies. PMID:26416797

  12. Concentration dynamics in lakes and reservoirs. Studies using radioactive tracers

    International Nuclear Information System (INIS)

    The use of radioactive tracers for the investigation of concentration dynamics of inert soluble matter in lakes and reservoirs is reviewed. Shallow and deep stratified lakes are considered. The mechanism of mixing in lakes, flow pattern and input - output response are discussed. The methodology of the use of radioactive tracers for concentration dynamic studies is described. Examples of various investigations are reviewed. The dynamics of shallow lakes can be found and expressed in terms of transfer functions, axial dispersion models, residence time distributions and sometimes only semiquantitative information about the flow pattern. The dynamics of deep, stratified lakes is more complex and difficult to investigate with tracers. Flow pattern, horizontal and vertical eddy diffusivities, mass transfer between the hypolimnion and epilimnion are tools used for describing this dynamics. (author)

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. Forced Gradient Tracer Tests In A Highly Permeable Fault Zone

    Science.gov (United States)

    Himmelsbach, T.; Hötzl, H.; Maloszewski, P.

    1994-03-01

    In the area of a planned dam site in the southern Black Forest, an observation tunnel with boreholes drilled into an adjacent vertically orientated ore body offered nearly ideal conditions to investigate transport phenomena in a highly permeable fault and fracture zone. The experimental array, consisting of horizontal and inclined boreholes lying within distances of ten to twelve meters apart, gave the opportunity to perform forced gradient tracer tests over varying distances under fixed hydraulic boundary conditions. The breakthrough curves of the tracer experiments were analyzed using an adequate transport model. The fitting procedure yielded hydraulic parameters such as fissure and matrix porosities and first estimations of the average fracture aperture.

  19. Radioactive γ/β tracer to explore dangerous technogenic phenomena

    Science.gov (United States)

    Nagorsky, P. M.; Yakovleva, V. S.; Makarov, E. O.; Firstov, P. P.; Kondratyeva, A. G.; Stepanenko, A. A.

    2016-06-01

    A radioactive γ/β tracer to explore dangerous technogenic phenomena has been proposed: the ratio of the measured flux density of β- and γ-radiations in the surface layer of the atmosphere. The time dependence analysis of the ratio of β- and γ-pulse count rate has been carried out. A significant increase of the γ/β ratio was recorded under the cyclone passing through Japan (Fukushima) to Kamchatka. The proposed γ/β tracer can be a very sensitive indicator of nonstationary processes related to hazardous natural and technogenic phenomena.

  20. 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

  1. Synthesis and evaluation of a peptide targeted small molecular Gd-DOTA monoamide conjugate for MR molecular imaging of prostate cancer

    OpenAIRE

    Wu, Xueming; Burden-Gulley, Susan M.; Yu, Guan-Ping; Tan, Mingqian; Lindner, Daniel; Brady-Kalnay, Susann M.; Lu, Zheng-Rong

    2012-01-01

    Tumor extracellular matrix has an abundance of cancer related proteins that can be used as biomarkers for cancer molecular imaging. Innovative design and development of safe and effective targeted contrast agents to these biomarkers would allow effective MR cancer molecular imaging with high spatial resolution. In this study, we synthesized a low molecular weight CLT1 peptide targeted Gd(III) chelate CLT1-dL-(Gd-DOTA)4 specific to clotted plasma proteins in tumor stroma for cancer MR molecula...

  2. 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.

  3. Identification and characterization of conservative organic tracers for use as hydrologic tracers for the Yucca Mountain Site characterization study

    International Nuclear Information System (INIS)

    This report is in two parts one for the fluorinated benzoic acids and one for the fluorinated aliphatic acids. The assumptions made in the report regarding the amount of tracer that will be used, dilution of the tracer during the test and the length of exposure (if any) to individuals drinking the water were made by the authors. These assumptions must really come from the USGS hydrologists in charge of the c-well tracer testing program. Accurate estimates of dilution of the tracer during the test are also important because of solubility limitations of some of the tracers. Three of the difluorobenzoic acids have relatively low solubilities and may not be usable if the dilution estimates are large. The toxicologist that reviewed the document agreed with our conclusion that the fluorinated benzoic and toluic acids do not represent a health hazard if used under the conditions as outlined in the report. We are currently testing 15 of these compounds, and if even if three difluorobenzoic acids cannot be used because of solubility limitations we will still have 12 tracers. The toxicologist felt that the aliphatic fluorinated acids potentially present more of a health risk than the aromatic. This assessment was based on the fact of a known allergic response to halothane anesthetic. This risk, although minimal, is known and he felt that was enough reason to recommend against their use. The authors feel that the toxicologists interpretation of this risk was overly conservative, however, we will not go against his recommendation at this time for the following reasons. First, without the aliphatic compounds we still have 12 to 15 fluorinated aromatic acids which, should be enough for the c-well tests. Second, to get a permit to use aliphatic compounds would undoubtedly require a hearing which could be quite lengthy

  4. 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.

  5. Recent advances in chemical engineering. Tracers and tracing methods

    International Nuclear Information System (INIS)

    The first congress on 'tracers and tracing methods' has taken place in Nancy in November 1998. It has been a successful national event with more than 100 participants and 65 presentations. The applications of radiotracers in different industries have been studied. The target participants were the researchers, engineers and technologists of various industrial and research sectors

  6. Mathematical models for interpretation of tracer data in groundwater hydrology

    International Nuclear Information System (INIS)

    The Advisory Group Meeting had the overall objective of discussing in detail the methodologies and approaches in the development of mathematical models for quantitative evaluations of tracer data in groundwater hydrology and reviewing the recent advances in this field. A separate abstract was prepared for each of the eight papers

  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. Measurement of mean transit time with radioactive tracers

    International Nuclear Information System (INIS)

    The purpose of this work was to validate the use of moment to computer transit time in radioactive tracer studies. In tracer dilution studies, input and output functions usually can be described by means of exponential and gamma-variate functions. The authors demonstrated mathematically that computation of transit time with use of the first moments of these modeling functions is equivalent to the use of impulse response functions. They used a test object that would emulate the transit time of pulmonary blood flow in a medium-size dog to validate the computation of transit time with the first moment. A bolus of 185 MBq (5 mCi) of Tc-99m pertechnetate was injected. The quality of the bolus injection was modified by changing the size of the bolus. The transit time obtained from the first moments of the tracer-dilution curves was in agreement with the first moments of the modeling mathematical functions. Transit time is radionuclide studies can be computed from either the first moment of the tracer-dilution curve or of the modeling mathematical functions. Derivation of the impulse response function is not necessary

  9. 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...

  10. Tracers for investigating pathogen fate and removal mechanisms in mesocosms

    International Nuclear Information System (INIS)

    The purpose of the present investigation has been to develop a tracer suite that has application in in-situ assessment and optimization of physical and biological removal and elimination mechanisms of pathogens within laboratory scale biological treatment systems. The tracer suite includes three pathogen indicators, namely, a conserved non-viable particle (fluorescently labelled microspheres, FLM), a non-conserved non-viable particle (fluorescently labelled bioparticles, FLB), and a non-conserved viable particle (Nalidixic acid resistant E. coli, NAREC). The tracer triplet principles were developed with practical experiments on planted, and unplanted subsurface flow wetland mesocosms treating a synthetic domestic wastewater. The tracers monitor for physical removal mechanisms (FLM), elimination activity (FLB), and removal thresholds (NAREC). FLM enumeration was simplified by calibration of particle concentration with respect to acetone-extractable fluorescence. Similarly, FLB elimination was assessed by bulk fluorescence using two characteristic excitation-emission wavelength pairs: 494/519 and 220/319 nm. NAREC results indicated that first order removal kinetics may only proceed down to limiting threshold concentrations

  11. 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

  12. 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.

  13. Optimization of water treatment facility by using radioisotope tracer

    Energy Technology Data Exchange (ETDEWEB)

    Jin, J. H.; Lee, M. J.; Jung, S. H.

    1997-01-01

    In order to get the optimization of conventional water treatment facility, radioisotope tracer technique was applied. It is desirable to set the baffles inside of mixing basin for the enhancement of mixing effect. It was appeared that most of flocs were settled down within 60 - 70 % of total length of sedimentation basin even with high flow rate. (author). 2 tabs., 32 figs.

  14. 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)

  15. Use of dual isotope tracers in biomedical research

    NARCIS (Netherlands)

    Stellaard, F

    2005-01-01

    Biomedical stable isotope studies involve administration of tracer and measurement of isotope enrichment in blood, urine, feces or breath. The aim of the studies is to gather quantitative information about a specific metabolic function. However, the measured isotope enrichment may be affected by oth

  16. TRAC, a collaborative computer tool for tracer-test interpretation

    Directory of Open Access Journals (Sweden)

    Fécamp C.

    2013-05-01

    Full Text Available 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.

  17. Radiation dose estimates for carbon-11-labelled PET tracers

    International Nuclear Information System (INIS)

    Introduction: Carbon-11-labelled positron emission tomography (PET) tracers commonly used in biomedical research expose subjects to ionising radiation. Dosimetry is the measurement of radiation dose, but also commonly refers to the estimation of health risk associated with ionising radiation. This review describes radiation dosimetry of carbon-11-labelled molecules in the context of current PET research and the most widely used regulatory guidelines. Methods: A MEDLINE literature search returned 42 articles; 32 of these were based on human PET data dealing with radiation dosimetry of carbon-11 molecules. Radiation burden expressed as effective dose and maximum absorbed organ dose was compared between tracers. Results: All but one of the carbon-11-labelled PET tracers have an effective dose under 9 μSv/MBq, with a mean of 5.9 μSv/MBq. Data show that serial PET scans in a single subject are feasible for the majority of radiotracers. Conclusion: Although differing in approach, the two most widely used regulatory frameworks (those in the USA and the EU) do not differ substantially with regard to the maximum allowable injected activity per PET study. The predictive validity of animal dosimetry models is critically discussed in relation to human dosimetry. Finally, empirical PET data are related to human dose estimates based on homogenous distribution, generic models and maximum cumulated activities. Despite the contribution of these models to general risk estimation, human dosimetry studies are recommended where continued use of a new PET tracer is foreseen.

  18. Aluminum-26 as a biological tracer using accelerator mass spectrometry

    Science.gov (United States)

    Flarend, Richard Edward

    1997-06-01

    The development of accelerator mass spectrometry (AMS) has provided a practical method of detection for the only isotope of aluminum suitable as a tracer, 26Al. The use of 26Al as a tracer for aluminum has made possible the study of aluminum metabolism and the pharmacokinetics of aluminum-containing drugs at physiological levels. An overview of the various advantages of using 26Al as a tracer for aluminum and a general description of the AMS technique as applied to bio-medical applications is given. To illustrate the versatility of 26Al as a tracer for aluminum, 26Al studies of the past several years are discussed briefly. In addition, Two novel investigations dealing with 26Al-labeled drugs will be presented in more detail. In one of these studies, it was found that 26Al from aluminum hydroxide and aluminum phosphate vaccine adjuvants appeared in the blood just one hour after intramuscular injection. This is a surprising result since the currently held theory of how adjuvants work assumes that adjuvants remain insoluble and hold the antigen at the injection site for a long period of time. In another project, 26Al-labeled antiperspirants are being characterized by combining AMS with traditional analytical and chromatographic techniques. Future directions for this and other possible studies are discussed.

  19. Development of Kinetic Interface Sensitive Tracers (KIS-Tracer) for Supercritical Carbon Dioxide Injections into Deep Saline Aquifers

    Science.gov (United States)

    Schaffer, M.; Maier, F.; Licha, T.; Sauter, M.

    2012-04-01

    The storage of captured CO2 into geological formations is recently one of the most promising technologies to mitigate anthropogenic greenhouse gas emissions into the earth's atmosphere. Deep saline aquifers are considered as the most potential sequestration sites of CO2 due to their huge storage capacities of several thousand Gt. Ongoing research deals mainly with the investigation of relevant physico-chemical processes, the fate of CO2 and the risk assessment during and after supercritical CO2 (scCO2) injections. The occurring processes at the interface between injected scCO2 and formation brine play a major role to evaluate the fate and behavior of scCO2 in the reservoir. This is because the interface represents a reactive zone where numerous physico-chemical processes like dissolution of scCO2 in water as well as dissolution and precipitation of minerals take place. In most cases it is desired to maximize the interface size to increase the storage efficiency. Therefore, knowledge on interface size and dynamics would allow the observation of plume spreading and the detection of mixing or fingering effects. In order to gain this information innovative tracers are necessary which are able to quantify the temporal and spatial development of scCO2/water interfaces. As a result, it may be possible to assess the storage efficiency and to optimize subsequent injections. Up to now, such time-dependent tracers for reservoir studies are not available and limited to equilibrium tracers (known as partitioning and interfacial tracers, respectively). Therefore, novel reactive tracers (KIS-Tracers) are developed to overcome this gap. The idea is to find suitable molecules which allow the implementation of a defined chemical reaction at the interface. Due to the known kinetic constants the change of interface size can be characterized over time. The new tracer is injected together with the supercritical CO2 (scCO2) into a deep saline aquifer. Afterwards, the tracer adsorbs at

  20. 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.

  1. Single-scan dual-tracer FLT+FDG PET tumor characterization

    Science.gov (United States)

    Kadrmas, Dan J.; Rust, Thomas C.; Hoffman, John M.

    2013-02-01

    Rapid multi-tracer PET aims to image two or more tracers in a single scan, simultaneously characterizing multiple aspects of physiology and function without the need for repeat imaging visits. Using dynamic imaging with staggered injections, constraints on the kinetic behavior of each tracer are applied to recover individual-tracer measures from the multi-tracer PET signal. The ability to rapidly and reliably image both 18F-fluorodeoxyglucose (FDG) and 18F-fluorothymidine (FLT) would provide complementary measures of tumor metabolism and proliferative activity, with important applications in guiding oncologic treatment decisions and assessing response. However, this tracer combination presents one of the most challenging dual-tracer signal-separation problems—both tracers have the same radioactive half-life, and the injection delay is short relative to the half-life and tracer kinetics. This work investigates techniques for single-scan dual-tracer FLT+FDG PET tumor imaging, characterizing the performance of recovering static and dynamic imaging measures for each tracer from dual-tracer datasets. Simulation studies were performed to characterize dual-tracer signal-separation performance for imaging protocols with both injection orders and injection delays of 10-60 min. Better performance was observed when FLT was administered first, and longer delays before administration of FDG provided more robust signal-separation and recovery of the single-tracer imaging measures. An injection delay of 30 min led to good recovery (R > 0.96) of static image values (e.g. SUV), Knet, and K1 as compared to values from separate, single-tracer time-activity curves. Recovery of higher order rate parameters (k2, k3) was less robust, indicating that information regarding these parameters was harder to recover in the presence of statistical noise and dual-tracer effects. Performance of the dual-tracer FLT(0 min)+FDG(32 min) technique was further evaluated using PET/CT imaging studies in

  2. Numerical simulations of the spread of floating passive tracer released at the Old Harry prospect

    International Nuclear Information System (INIS)

    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

  3. Greenland freshwater pathways in the sub-Arctic Seas from model experiments with passive tracers

    Science.gov (United States)

    Dukhovskoy, Dmitry S.; Myers, Paul G.; Platov, Gennady; Timmermans, Mary-Louise; Curry, Beth; Proshutinsky, Andrey; Bamber, Jonathan L.; Chassignet, Eric; Hu, Xianmin; Lee, Craig M.; Somavilla, Raquel

    2016-01-01

    Accelerating since the early 1990s, the Greenland Ice Sheet mass loss exerts a significant impact on thermohaline processes in the sub-Arctic seas. Surplus freshwater discharge from Greenland since the 1990s, comparable in volume to the amount of freshwater present during the Great Salinity Anomaly events, could spread and accumulate in the sub-Arctic seas, influencing convective processes there. However, hydrographic observations in the Labrador Sea and the Nordic Seas, where the Greenland freshening signal might be expected to propagate, do not show a persistent freshening in the upper ocean during last two decades. This raises the question of where the surplus Greenland freshwater has propagated. In order to investigate the fate, pathways, and propagation rate of Greenland meltwater in the sub-Arctic seas, several numerical experiments using a passive tracer to track the spreading of Greenland freshwater have been conducted as a part of the Forum for Arctic Ocean Modeling and Observational Synthesis effort. The models show that Greenland freshwater propagates and accumulates in the sub-Arctic seas, although the models disagree on the amount of tracer propagation into the convective regions. Results highlight the differences in simulated physical mechanisms at play in different models and underscore the continued importance of intercomparison studies. It is estimated that surplus Greenland freshwater flux should have caused a salinity decrease by 0.06-0.08 in the sub-Arctic seas in contradiction with the recently observed salinification (by 0.15-0.2) in the region. It is surmised that the increasing salinity of Atlantic Water has obscured the freshening signal.

  4. 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.

  5. Dynamics of passive tracers in a bath of self-propelling granular particles

    Science.gov (United States)

    Hamoy, E.; Confesor, M. N.

    2015-06-01

    We report on our experimental investigation of the dynamics of a passive tracer in a bath of active self-propelling granular particles. We found a caging like dynamics of the passive tracer such that for low active particle concentrations the passive tracer exhibits longer periods of inactivity. For increasing active particle concentration the occurrence of short period inactivity increases.

  6. Quantification of methane emissions from 15 Danish landfills using the mobile tracer dispersion method

    DEFF Research Database (Denmark)

    Mønster, Jacob; Samuelsson, Jerker; Kjeldsen, Peter;

    2015-01-01

    Whole-site methane emissions from 15 Danish landfills were assessed using a mobile tracer dispersion method with either Fourier transform infrared spectroscopy (FFIR), using nitrous oxide as a tracer gas, or cavity ring-down spectrometry (CRDS), using acetylene as a tracer gas. The landfills were...

  7. Sol-gel synthesis of magnetic TiO2 microspheres and characterization of their in vitro heating ability for hyperthermia treatment of cancer

    OpenAIRE

    Liu, Gengci; Kawashita, Masakazu; Li, Zhixia; Miyazaki, Toshiki; Kanetaka, Hiroyasu

    2015-01-01

    Common cancer treatments are invasive and lack specificity, leading to unwanted side effects. Because hyperthermia can kill cancer cells and damage proteins and structures within cells, it has been considered a novel, minimally invasive cancer treatment. However, many hyperthermia treatments cannot heat deep-seated tumors effectively and locally. Heat-generating magnetic microspheres can help address this challenge. However, current research has not produced microspheres that can be sufficien...

  8. 'Serial review on clinical PET tracers'. Positron emission tomography with [11C]2-β-carbomethoxy-3β-(4-fluorophenyl) tropane for dopamine transporter

    International Nuclear Information System (INIS)

    [11C]2-β-carbomethoxy-3β-(4-fluorophenyl)tropane (11C-CFT) is a new radiotracer with a cocaine-structure and binds specifically to dopamine transporter located on the presynaptic dopaminergic terminal, which gives us in vivo information on dopamine transporter binding. The selectivity of 11C-CFT to the target region and the specificity of 11C-CFT is considerably high. The synthesis of the tracer is fairly stable. With these qualities, the tracer enables to illustrate the pathophysiology of Parkinson's disease (PD) or differentiate PD from brain disorders with Parkinsonisms. Moreover, it has been now in extensive use for other neurological and psychiatric diseases with dopaminergic abnormality. The clinical usefulness of 11C-CFT is described here. (author)

  9. Design and synthesis of an in vivo-efficacious PIM3 kinase inhibitor as a candidate anti-pancreatic cancer agent.

    Science.gov (United States)

    Nakano, Hirofumi; Hasegawa, Tsukasa; Saito, Nae; Furukawa, Kaoru; Mukaida, Naofumi; Kojima, Hirotatsu; Okabe, Takayoshi; Nagano, Tetsuo

    2015-12-15

    Serine/threonine kinase PIM3 is a potential therapeutic target for pancreatic cancer. Here, we describe the evolution of our previous PIM1 inhibitor 1 into PIM3 inhibitor 11 guided by use of the crystal structure of PIM1 as a surrogate to provide a basis for rational modification. Compound 11 potently inhibits PIM3 kinase activity, as well as growth of several pancreatic cancer cell lines. In a mouse xenograft model, 11 inhibited growth of human pancreatic cancer cell line PCI66 with negligible body weight loss. Thus, 11 appears to be a promising lead compound for further optimization to develop new anti-pancreatic cancer agents. PMID:26547690

  10. Collective dynamics effect transient subdiffusion of inert tracers in flexible gel networks

    Science.gov (United States)

    Godec, Aljaž; Bauer, Maximilian; Metzler, Ralf

    2014-09-01

    Based on extensive Brownian dynamics simulations we study the thermal motion of a tracer bead in a cross-linked, flexible gel in the limit when the tracer particle size is comparable to or even larger than the equilibrium mesh size of the gel. The analysis of long individual trajectories of the tracer demonstrates the existence of pronounced transient anomalous diffusion. From the time averaged mean squared displacement and the time averaged van Hove correlation functions we elucidate the many-body origin of the non-Brownian tracer bead dynamics. Our results shed new light onto the ongoing debate over the physical origin of steric tracer interactions with structured environments.

  11. 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)

  12. 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...

  13. 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...

  14. 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...

  15. Contributions to hydrological tracer methods and their application

    International Nuclear Information System (INIS)

    The activities of the Institut fuer Radiohydrometrie of the GSF are mainly devoted to the field of environmental research studying the quality, use and protection from pollution of drinking water which has become scarce in many parts of the world. The knowledge and experience of a variety of scientific disciplines are combined to the common task of developing new tracer methods and selecting suitable hydrogeological methods to allow quantitative studies of the hydrological cycle, from rainfall to surface or sub-surface run-off. The tracers used in these studies are for the most part stable, natural radioisotopes occurring in the hydrological cycle, as well as fluorescent dyes or radionuclides for water labelling. The contributions collected in this volume are grouped according to the above outline of tasks and present a survey of current methods and measurements, illustrating their efficiency in solving hydrological problems. (orig./RW)

  16. 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.

  17. 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.

  18. In-EDTA as activable tracer in hydrogeological investigations

    International Nuclear Information System (INIS)

    Two experiments are presented, on the possibilities of the use of indium in the form of the In-EDTA complex, as an activable tracer for hydrogeological studies. The determination of indium concentrations in the sampled water has been carried out by using the coprecipitation of indium with bismuth hydroxide, the neutron activation at the VVR-S reactor of the Institute for Nuclear Physics and Engineering - Bucharest and the measurement on the 417.0 keV line of sup(116m)In with the Ge(Li) spectrometric device. The advantages of the utilization of In-EDTA as a tracer for marking large volumes of water and of some long transit waters (of the order of months) have resulted. (authors)

  19. Synthesis and biological evaluation of some novel triazole hybrids of curcumin mimics and their selective anticancer activity against breast and prostate cancer cell lines.

    Science.gov (United States)

    Mandalapu, Dhanaraju; Saini, Karan S; Gupta, Sonal; Sharma, Vikas; Yaseen Malik, Mohd; Chaturvedi, Swati; Bala, Veenu; Hamidullah; Thakur, Subhadra; Maikhuri, Jagdamba P; Wahajuddin, Muhammad; Konwar, Rituraj; Gupta, Gopal; Sharma, Vishnu Lal

    2016-09-01

    The anti-cancer property of curcumin, an active component of turmeric, is limited due to its poor solubility, stability and bioavailability. To enhance its efficacy, we designed a novel series of twenty-four monocarbonyl curcumin analogue-1,2,3-triazole conjugates and evaluated their anti-cancer activity towards endocrine related cancers. The new compounds (17-40) were synthesized through CuAAC click reaction and SAR analysis carried out. Out of these all, compound 17 showed most significant anti-cancer activity against prostate cancer cells with IC50 values of 8.8μM and 9.5μM in PC-3 and DU-145 cells, respectively. Another compound 26 showed significant anti-cancer activity against breast cancer cells with IC50 of 6μM, 10μM and 6.4μM in MCF-7, MDA-MB-231 and 4T1 cells, respectively while maintaining low toxicity towards non-cancer originated cell line, HEK-293. Compounds 17 and 26 arrested cell cycle and induced mitochondria-mediated apoptosis in cancer cells. Further, both of these compounds significantly down-regulated cell proliferation marker (PCNA), inhibited activation of cell survival protein (Akt phosphorylation), upregulated pro-apoptotic protein (Bax) and down-regulated anti-apoptotic protein (Bcl-2) in their respective cell lines. In addition, in vitro stability, solubility and plasma binding studies of the compounds 17 and 26 showed them to be metabolically stable. Thus, this study identified two new curcumin monocarbonyl-1,2,3-triazole conjugate compounds with more potent activity than curcumin against breast and prostate cancers. PMID:27496212

  20. 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

  1. 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...

  2. Ready for prime time? Dual tracer PET and SPECT imaging

    OpenAIRE

    Fakhri, Georges El

    2012-01-01

    Dual isotope single photon emission computed tomography (SPECT) and dual tracer positron emission tomography (PET) imaging have great potential in clinical and molecular applications in the pediatric as well as the adult populations in many areas of brain, cardiac, and oncologic imaging as it allows the exploration of different physiological and molecular functions (e.g., perfusion, neurotransmission, metabolism, apoptosis, angiogenesis) under the same physiological and physical conditions. T...

  3. PET and SPET tracers for mapping the cardiac nervous system

    International Nuclear Information System (INIS)

    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-[18F]fluorodopamine, (-)-6-[18F]fluoronorepinephrine and (-)-[11C]epinephrine, and radiolabelled catecholamine analogues, such as [123I]meta-iodobenzylguanidine, [11C]meta-hydroxyephedrine, [18F]fluorometaraminol, [11C]phenylephrine and meta-[76Br]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 (-)-[18F]fluoroethoxybenzovesamicol display a high degree of non-specific binding in myocardium which restricts their utility for cardiac neuronal imaging. (orig.)

  4. Reintegration of child soldiers in Burundi: a tracer study

    OpenAIRE

    Jordans Mark JD; Komproe Ivan H; Tol Wietse A; Ndayisaba Aline; Nisabwe Theodora; Kohrt Brandon A

    2012-01-01

    Abstract Background Substantial attention and resources are aimed at the reintegration of child soldiers, yet rigorous evaluations are rare. Methods This tracer study was conducted among former child soldiers (N=452) and never-recruited peers (N=191) who participated in an economic support program in Burundi. Socio-economic outcome indicators were measured retrospectively for the period before receiving support (T1; 2005–06); immediately afterwards (T2; 2006–07); and at present (T3; 2010). Pa...

  5. Plants and their relationship to soil moisture and tracer movement

    International Nuclear Information System (INIS)

    To obtain a better understanding of the mechanisms for possible movement of radionuclides or other toxic materials from waste burial sites in arid to semiarid regions, changes in soil moisture and tracer (Co, Cs, Sr, and tritium) movement were compared for bare vs vegetated soils. During the course of two growing seasons, comparing vegetated with bare soils, plant transpiration processes significantly reduced the soil moisture. In the vegetated soils, most of the Co, Cs, and Sr remained in the region of original emplacement. In bare soils, Co and Cs underwent minimum movement, but the peak concentration of Sr moved downward. For all tracers in the vegetated soils, there was some evidence that slight amounts of tracer had been absorbed in the plant roots and brought to the surface through plant translocation processes. In all cases, there was no significant upward movement of Co, Cs, and Sr. For tritium, the vegetated soils, compared with the bare soils, retained the maximum inventories near the original emplacement location. Although all soils showed some tritium loss, it was greatest in the vegetated soils. A literature review associated with the experiment indicated that plant species alone does not determine rooting depth, rate of transpiration, nutrient uptake, and other plant-associated processes. Environmental conditions are just as important as plant species and must be included in modeling plant-related effects. More data are needed on the effects of tracer concentration, soil water composition, variations in precipitation with time and intensity, evaporation rates, variations in soil composition, soil microorganisms, other invertebrates and vertebrates that inhabit soils, litter decay, and colloid movement on contaminant movement under conditions of unsaturated flow

  6. 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.

  7. Hanford 100-N Area Tracer Study Final Report

    International Nuclear Information System (INIS)

    This document provides an engineering tracer study final report for the determination of contact time for the disinfection process at Group A Nontransient Noncommunity water treatment plant for the 100- N Water Plant (located on the Hanford Site in Richland, Washington). The purpose of this study is to determine the actual detention time within the plant clearwell, and the disinfection contact time at several clearwell effluent flow rates

  8. SPHRAY: A Smoothed Particle Hydrodynamics Ray Tracer for Radiative Transfer

    OpenAIRE

    Altay, Gabriel; Rupert A. C. Croft(Bruce and Astrid McWilliams Center for Cosmology, Department of Physics, Carnegie Mellon University, 5000 Forbes Ave, Pittsburgh, PA 15213, USA); Pelupessy, Inti

    2008-01-01

    We introduce SPHRAY, a Smoothed Particle Hydrodynamics (SPH) ray tracer designed to solve the 3D, time dependent, radiative transfer (RT) equations for arbitrary density fields. The SPH nature of SPHRAY makes the incorporation of separate hydrodynamics and gravity solvers very natural. SPHRAY relies on a Monte Carlo (MC) ray tracing scheme that does not interpolate the SPH particles onto a grid but instead integrates directly through the SPH kernels. Given initial conditions and a description...

  9. 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.

  10. 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

  11. Calibration of a groundwater flow model with different tracer technologies

    International Nuclear Information System (INIS)

    Full text: This study developed a mechanism to calibrate a regional groundwater flow model for an aquifer system in central Mexico (Guanajuato) by residence time values of a set of different tracers. The used tracers were carbon-14, tritium, chlorofluorocarbons (CFCs), and sulfur hexafluoride (SF6). The applied program for the flow simulations was the modular finite-difference MODFLOW-2000, coupled to the transport model MODPATH. The local recharge estimates obtained from the chloride mass-balance method were regionalised by a Kriging method, whilst hydraulic conductivity values for each geological unit were interpreted from pumping test data. The flow simulation was considered in steady-state conditions (pre-development model). Since the flow domain was complicate and the number of grid cells large, an algebraic multigrid solver was applied rather than the classical iterative methods. The calibration process consisted in adjusting the hydraulic conductivity values until (a) the calculated head distribution matched the observed water level measurements, and (b) the flow balance is satisfied in the whole flow domain (mass balance) and in parts of the flow domain (zone budget), (c) the mean residence time values of carbon-14, tritium, CFCs, and SF6 matched the time of travel of corresponding particles in the flow domain. Since carbon-14 is known to be modified due to geochemical interactions with the aquifer material, a preceding correction by using the program PHREEQC was necessary to obtain reliable mean residence time values. Due to the low time resolution, the tracers for young groundwater (tritium, CFCs, SF6) could be applied in the flow simulation only to indicate if the groundwater is younger or older than 40 to 50 years. This calibration approach was not only useful to quantitatively describe the flow regime of an aquifer system, but also to make some observations to its vulnerability. Comments on the experience of the used tracer technologies in combination

  12. 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.

  13. Waste tank ventilation rates measured with a tracer gas method

    International Nuclear Information System (INIS)

    Passive ventilation with the atmosphere is used to prevent accumulation of waste gases and vapors in the headspaces of 132 of the 177 high-level radioactive waste Tanks at the Hanford Site in Southeastern Washington State. Measurements of the passive ventilation rates are needed for the resolution of two key safety issues associated with the rates of flammable gas production and accumulation and the rates at which organic salt-nitrate salt mixtures dry out. Direct measurement of passive ventilation rates using mass flow meters is not feasible because ventilation occurs va multiple pathways to the atmosphere (i.e., via the filtered breather riser and unsealed tank risers and pits), as well as via underground connections to other tanks, junction boxes, and inactive ventilation systems. The tracer gas method discussed in this report provides a direct measurement of the rate at which gases are removed by ventilation and an indirect measurement of the ventilation rate. The tracer gas behaves as a surrogate of the waste-generated gases, but it is only diminished via ventilation, whereas the waste gases are continuously released by the waste and may be subject to depletion mechanisms other than ventilation. The fiscal year 1998 tracer studies provide new evidence that significant exchange of air occurs between tanks via the underground cascade pipes. Most of the single-shell waste tanks are connected via 7.6-cm diameter cascade pipes to one or two adjacent tanks. Tracer gas studies of the Tank U-102/U-103 system indicated that the ventilation occurring via the cascade line could be a significant fraction of the total ventilation. In this two-tank cascade, air evidently flowed from Tank U-103 to Tank U-102 for a time and then was observed to flow from Tank U-102 to Tank U-103

  14. 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.

  15. Entropically induced asymmetric passage times of charged tracers across corrugated channels

    Science.gov (United States)

    Malgaretti, Paolo; Pagonabarraga, Ignacio; Miguel Rubi, J.

    2016-01-01

    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.

  16. Dosimetry of 64Cu-DOTA-AE105, a PET tracer for uPAR imaging

    International Nuclear Information System (INIS)

    64Cu-DOTA-AE105 is a novel positron emission tomography (PET) tracer specific to the human urokinase-type plasminogen activator receptor (uPAR). In preparation of using this tracer in humans, as a new promising method to distinguish between indolent and aggressive cancers, we have performed PET studies in mice to evaluate the in vivo biodistribution and estimate human dosimetry of 64Cu-DOTA-AE105. Methods: Five mice received iv tail injection of 64Cu-DOTA-AE105 and were PET/CT scanned 1, 4.5 and 22 h post injection. Volume-of-interest (VOI) were manually drawn on the following organs: heart, lung, liver, kidney, spleen, intestine, muscle, bone and bladder. The activity concentrations in the mentioned organs [%ID/g] were used for the dosimetry calculation. The %ID/g of each organ at 1, 4.5 and 22 h was scaled to human value based on a difference between organ and body weights. The scaled values were then exported to OLINDA software for computation of the human absorbed doses. The residence times as well as effective dose equivalent for male and female could be obtained for each organ. To validate this approach, of human projection using mouse data, five mice received iv tail injection of another 64Cu-DOTA peptide-based tracer, 64Cu-DOTA-TATE, and underwent same procedure as just described. The human dosimetry estimates were then compared with observed human dosimetry estimate recently found in a first-in-man study using 64Cu-DOTA-TATE. Results: Human estimates of 64Cu-DOTA-AE105 revealed the heart wall to receive the highest dose (0.0918 mSv/MBq) followed by the liver (0.0815 mSv/MBq), All other organs/tissue were estimated to receive doses in the range of 0.02–0.04 mSv/MBq. The mean effective whole-body dose of 64Cu-DOTA-AE105 was estimated to be 0.0317 mSv/MBq. Relatively good correlation between human predicted and observed dosimetry estimates for 64Cu-DOTA-TATE was found. Importantly, the effective whole body dose was predicted with very high precision

  17. Metal stable isotope signatures as tracers in environmental geochemistry.

    Science.gov (United States)

    Wiederhold, Jan G

    2015-03-01

    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. PMID:25640608

  18. Analysis of radiolabelled thiocyanate tracer in oil field brines

    International Nuclear Information System (INIS)

    Thiocyanate (SCN-) labelled with 14C or 35S is applicable for the tracing of the water flow in water-driven oil production. This work describes two improved methods for increasing the concentration of S14CN- with sample sizes up to 1000 ml of sampled brine. The radioactivity detection is carried out by low-background liquid scintillation counting using standard-size counting vials of 20 ml. The first method is based on solvent extraction: two extraction/strip steps reduce the volume by the required factor of 100 down to 10 ml. The extraction agent is 0.5M tri-isooctylamine (TiOA) in Solvesso-150 and the stripping agent is 5M NH3. A chemical yield of 70-75%, a somewhat unfavourable quenching factor and a moderate reproducibility lead to a detection limit LD of 0.04 Bq/1. The second method is based on anion exchange. 1000 ml tracer-containing brine may be loaded onto 6.1 ml of the anion-exchange resin AG1-x8 before significant breakthrough of the tracer. More than 98.4% is absorbed. By elution with 2.8M sodiumperchlorate, more than 99.5% of the absorbed tracer is concentrated in a sharp elution peak of 10 ml. With a total chemical yield of 98%, a lower quenching factor and higher reproducibility than for the solvent extraction method, an LD-value of 0.005 Bq/1 is obtained. (orig.)

  19. 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...

  20. 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.

  1. 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)

  2. 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

  3. 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.

  4. Radon as tracer to identify discharge sections at Juatuba basin

    International Nuclear Information System (INIS)

    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, 222Rn, noble gas derived from natural sources, been found in all underground waters, as a product of radioactive decay of the 226Ra. This gas can be found in the air, water, rocks or soil. In this paper, the 222Rn 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 222Rn measurements at Fundao stream were carried out using the equipment RAD 7. The results showed that 222Rn 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)

  5. 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...

  6. Microbubbles and Microparticles are Not Faithful Tracers of Turbulent Acceleration

    Science.gov (United States)

    Mathai, Varghese; Calzavarini, Enrico; Brons, Jon; Sun, Chao; Lohse, Detlef

    2016-07-01

    We report on the Lagrangian statistics of acceleration of small (sub-Kolmogorov) bubbles and tracer particles with Stokes number St ≪1 in turbulent flow. At a decreasing Reynolds number, the bubble accelerations show deviations from that of tracer particles; i.e., they deviate from the Heisenberg-Yaglom prediction and show a quicker decorrelation despite their small size and minute St. Using direct numerical simulations, we show that these effects arise due the drift of these particles through the turbulent flow. We theoretically predict this gravity-driven effect for developed isotropic turbulence, with the ratio of Stokes to Froude number or equivalently the particle drift velocity governing the enhancement of acceleration variance and the reductions in correlation time and intermittency. Our predictions are in good agreement with experimental and numerical results. The present findings are relevant to a range of scenarios encompassing tiny bubbles and droplets that drift through the turbulent oceans and the atmosphere. They also question the common usage of microbubbles and microdroplets as tracers in turbulence research.

  7. Use of Helium-3 and Tritium tracers in oceanography

    International Nuclear Information System (INIS)

    As tritium considered as a transient tracer has become one of the most promising tool for the study of oceanic circulation and of the ocean capacity to absorb anthropogenic carbon, and as the simultaneous use of its radioactive descendant, Helium-3, brings an additional information (together, these tracers build up a clock in the study of water masses), and as all helium-3 and tritium measurements are made by mass spectroscopy, this research thesis addresses the analytical process, the detection limit, and the method reproducibility associated with this use of both tracers. The author reports and discusses helium-3 data obtained during a measurement campaign which allowed the localisation of an active source and the evidence of an intermediate back current, and tritium data obtained during another measurement campaign which allowed the description of the high time variability of convection processes, and an assessment of water renewal delays and of some deep water circulations. He also reports and discusses the simultaneous use of helium-3 data and tritium data to localize areas where convection processes occur. A theoretical approach to this simultaneous use is proposed which uses a mixing model which distinguishes the venting transit time. Measurement campaigns were performed in Red Sea, western Mediterranean Sea, and north-eastern Atlantic Ocean

  8. 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

  9. 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)

  10. Ascofuranone suppresses EGF-induced HIF-1α protein synthesis by inhibition of the Akt/mTOR/p70S6K pathway in MDA-MB-231 breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Yun-Jeong; Cho, Hyun-Ji [Research Institute of Biomedical Engineering and Department of Medicine, Catholic University of Daegu School of Medicine, Daegu 705-718 (Korea, Republic of); Magae, Junji [Magae Bioscience Institute, 49-4 Fujimidai, Tsukuba 300-1263 (Japan); Lee, In-Kyu [Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu 700-721 (Korea, Republic of); Park, Keun-Gyu, E-mail: kpark@knu.ac.kr [Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu 700-721 (Korea, Republic of); Chang, Young-Chae, E-mail: ycchang@cu.ac.kr [Research Institute of Biomedical Engineering and Department of Medicine, Catholic University of Daegu School of Medicine, Daegu 705-718 (Korea, Republic of)

    2013-12-15

    Hypoxia-inducible factor (HIF)-1 plays an important role in tumor progression, angiogenesis and metastasis. In this study, we investigated the potential molecular mechanisms underlying the anti-angiogenic effect of ascofuranone, an isoprenoid antibiotic from Ascochyta viciae, in epidermal growth factor (EGF)-1 responsive human breast cancer cells. Ascofuranone significantly and selectively suppressed EGF-induced HIF-1α protein accumulation, whereas it did not affect the expression of HIF-1β. Furthermore, ascofuranone inhibited the transcriptional activation of vascular endothelial growth factor (VEGF) by reducing protein HIF-1α. Mechanistically, we found that the inhibitory effects of ascofuranone on HIF-1α protein expression are associated with the inhibition of synthesis HIF-1α through an EGF-dependent mechanism. In addition, ascofuranone suppressed EGF-induced phosphorylation of Akt/mTOR/p70S6 kinase, but the phosphorylation of ERK/JNK/p38 kinase was not affected by ascofuranone. These results suggest that ascofuranone suppresses EGF-induced HIF-1α protein translation through the inhibition of Akt/mTOR/p70S6 kinase signaling pathways and plays a novel role in the anti-angiogenic action. - Highlights: • Inhibitory effect of ascofuranone on HIF-1α expression is EGF-specific regulation. • Ascofuranone decreases HIF-1α protein synthesis through Akt/mTOR pathways. • Ascofuranone suppresses EGF-induced VEGF production and tumor angiogenesis.

  11. 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

  12. Preparation of 19-iodocholestrol labelled with I-125 and its study as a 'tracer' of plasma lipoprotein

    International Nuclear Information System (INIS)

    A technique of synthesis of the 19-iodocholesterol labelled with I-125, modified in some steps from other methods published previously, is described. We have obtained a product with high chemical (96%) and radiochemical (99,9%) purities. The yield was higher and the time necessary to prepare it was lower than other methods reported. The study of thermal and radiolytic stability showed that the 19-iodocholesterol-I-125 was not broken by autoradiolysis whereas the I-125 was separated from the molecule when the temperature was increased. The use of this 19-iodocholesterol-I-125 as a tracer of cholesterol of plasma lipoprotein showed some properties of LCAT and CETP and also showed the different capacity of VLDL and LDL to transport cholesteryl esters. (author) 105 refs

  13. Synthesis, characterization and biological evaluation of N-ferrocenylmethyl amino acid benzene carboxamide derivatives and N-ferrocenyl benzoyl amino alkane derivatives as anti-cancer agents.

    OpenAIRE

    Butler, William E.

    2012-01-01

    The aim of this research was to explore the structure-activity relationship (SAR) of ferrocenyl-bioconjugates. A series of N-(ferrocenylmethylamino acid)-fluorinated-benzene carboxamide derivatives and a series of N-(ferrocenyl)-benzoyl-aminoalkane derivatives have been synthesised, structurally characterised and biologically evaluated for their anti-proliferative activity on various cancer cell lines, principally, the (estrogen receptor positive) MCF-7 breast cancer cell line. The anti-c...

  14. Metabolites of Ginger Component [6]-Shogaol Remain Bioactive in Cancer Cells and Have Low Toxicity in Normal Cells: Chemical Synthesis and Biological Evaluation

    OpenAIRE

    Yingdong Zhu; Warin, Renaud F.; Soroka, Dominique N.; Huadong Chen; Shengmin Sang

    2013-01-01

    Our previous study found that [6]-shogaol, a major bioactive component in ginger, is extensively metabolized in cancer cells and in mice. It is unclear whether these metabolites retain bioactivity. The aim of the current study is to synthesize the major metabolites of [6]-shogaol and evaluate their inhibition of growth and induction of apoptosis in human cancer cells. Twelve metabolites of [6]-shogaol (M1, M2, and M4-M13) were successfully synthesized using simple and easily accessible chemic...

  15. Fasting induces anti-Warburg effect that increases respiration but reduces ATP-synthesis to promote apoptosis in colon cancer models

    OpenAIRE

    Bianchi, Giovanna; Martella, Roberto; Ravera, Silvia; Marini, Cecilia; Capitanio, Selene; Orengo, Annamaria; Emionite, Laura; Lavarello, Chiara; Amaro, Adriana; Petretto, Andrea; Pfeffer, Ulrich; Sambuceti, Gianmario; Pistoia, Vito; Raffaghello, Lizzia; Longo, Valter D.

    2015-01-01

    Tumor chemoresistance is associated with high aerobic glycolysis rates and reduced oxidative phosphorylation, a phenomenon called “Warburg effect” whose reversal could impair the ability of a wide range of cancer cells to survive in the presence or absence of chemotherapy. In previous studies, Short-term-starvation (STS) was shown to protect normal cells and organs but to sensitize different cancer cell types to chemotherapy but the mechanisms responsible for these effects are poorly understo...

  16. Omega 3 fatty acids chemosensitize multidrug resistant colon cancer cells by down-regulating cholesterol synthesis and altering detergent resistant membranes composition

    OpenAIRE

    Gelsomino, Giada; Corsetto, Paola A.; Campia, Ivana; Montorfano, Gigliola; Kopecka, Joanna; Castella, Barbara; Gazzano, Elena; Ghigo, Dario; Rizzo, Angela M; Riganti, Chiara

    2013-01-01

    Background The activity of P-glycoprotein (Pgp) and multidrug resistance related protein 1 (MRP1), two membrane transporters involved in multidrug resistance of colon cancer, is increased by high amounts of cholesterol in plasma membrane and detergent resistant membranes (DRMs). It has never been investigated whether omega 3 polyunsatured fatty acids (PUFAs), which modulate cholesterol homeostasis in dyslipidemic syndromes and have chemopreventive effects in colon cancer, may affect the respo...

  17. Radiolabelling and preliminary evaluation of 68Ga-tetrapyrrole derivatives as potential tracers for PET

    International Nuclear Information System (INIS)

    Tetrapyrroles are multisided natural products which are of relevance in clinical medicine. Owing to their specific accumulation in tumour tissue, porphyrins, metalloporphyrins and chlorins have been used as in photodynamic therapy and optical imaging. Moreover, their specific uptake into inflammatory atheromatous plaques via LDL endocytosis has been reported. The present study is concerned with the synthesis of 68Ga labelled porphyrin derivatives and an in vitro assessment of the utility of radiotracers in positron emission tomography. A set of five porphyrin derivatives were labelled using 68Ga from a commercially obtained radionuclide generator. Dedicated post-processing of the generator eluate was conducted to allow for labelling in aqueous media and also under anhydrous conditions. Challenge studies and incubation in human serum confirmed the stability of the tracers. Plasma protein binding was investigated in order to confirm the presence of freely diffusible radioligand in plasma. A preliminary microPET study in a tumour-bearing rat resulted in a clear visualisation of the tumour

  18. Cancer Statistics: Endometrial Cancer

    Science.gov (United States)

    ... a third party. HPF: Did You Know? Endometrial Cancer Endometrial Cancer - Did you know that endometrial cancer ... mfhs0vbvWi8?rel=0 SEER Stat Fact Sheets: Endometrial Cancer Expand All Collapse All Lifetime risk estimates are ...

  19. Development of an automated modular system for the synthesis of [11C]acetate

    DEFF Research Database (Denmark)

    Felicini, Chiara; Någren, Kjell; Berton, Andrea;

    2010-01-01

    Carboxylation reactions offer a straightforward method for the synthesis of carbon-11 labelled carboxylic acids. Among these, the preparation of carbon-11 (C)-acetate is receiving increasing attention because of diagnostic applications in oncology in addition to its well-established use as a prob...... for myocardial oxidative metabolism. Although a number of dedicated modules are commercially available, the development of the synthesis on flexible platforms would be beneficial to widen the number of tracers, in particular for preclinical assessment and testing....

  20. 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.