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Sample records for ii muon pdt

  1. The Muon system of the run II D0 detector

    SciTech Connect

    Abazov, V.M.; Acharya, B.S.; Alexeev, G.D.; Alkhazov, G.; Anosov, V.A.; Baldin, B.; Banerjee, S.; Bardon, O.; Bartlett, J.F.; Baturitsky, M.A.; Beutel, D.; Bezzubov, V.A.; Bodyagin, V.; Butler, J.M.; Cease, H.; Chi, E.; Denisov, D.; Denisov, S.P.; Diehl, H.T.; Doulas, S.; Dugad, S.R.; /Beijing, Inst. High Energy Phys. /Charles U. /Prague, Tech. U. /Prague, Inst. Phys. /San Francisco de Quito U. /Tata Inst. /Dubna, JINR /Moscow, ITEP /Moscow State U. /Serpukhov, IHEP /St. Petersburg, INP /Arizona U. /Florida State U. /Fermilab /Northern Illinois U. /Indiana U. /Boston U. /Northeastern U. /Brookhaven /Washington U., Seattle /Minsk, Inst. Nucl. Problems

    2005-03-01

    The authors describe the design, construction and performance of the upgraded D0 muon system for Run II of the Fermilab Tevatron collider. Significant improvements have been made to the major subsystems of the D0 muon detector: trigger scintillation counters, tracking detectors, and electronics. The Run II central muon detector has a new scintillation counter system inside the iron toroid and an improved scintillation counter system outside the iron toroid. In the forward region, new scintillation counter and tracking systems have been installed. Extensive shielding has been added in the forward region. A large fraction of the muon system electronics is also new.

  2. The muon system of the Run II DØ detector

    NASA Astrophysics Data System (ADS)

    Abazov, V. M.; Acharya, B. S.; Alexeev, G. D.; Alkhazov, G.; Anosov, V. A.; Baldin, B.; Banerjee, S.; Bardon, O.; Bartlett, J. F.; Baturitsky, M. A.; Beutel, D.; Bezzubov, V. A.; Bodyagin, V.; Butler, J. M.; Cease, H.; Chi, E.; Denisov, D.; Denisov, S. P.; Diehl, H. T.; Doulas, S.; Dugad, S. R.; Dvornikov, O. V.; Dyshkant, A.; Eads, M.; Evdokimov, A.; Evdokimov, V. N.; Fitzpatrick, T.; Fortner, M.; Gavrilov, V.; Gershtein, Y.; Golovtsov, V.; Gómez, B.; Goodwin, R.; Gornushkin, Yu. A.; Green, D. R.; Gupta, A.; Gurzhiev, S. N.; Gutierrez, G.; Haggerty, H.; Hanlet, P.; Hansen, S.; Hazen, E.; Hedin, D.; Hoeneisen, B.; Ito, A. S.; Jayanti, R.; Johns, K.; Jouravlev, N.; Kalinin, A. M.; Kalmani, S. D.; Kharzheev, Y. N.; Kirsch, N.; Komissarov, E. V.; Korablev, V. M.; Kostritsky, A.; Kozelov, A. V.; Kozlovsky, M.; Kravchuk, N. P.; Krishnaswamy, M. R.; Kuchinsky, N. A.; Kuleshov, S.; Kupco, A.; Larwill, M.; Leitner, R.; Lipaev, V. V.; Lobodenko, A.; Lokajicek, M.; Lubatti, H. J.; Machado, E.; Maity, M.; Malyshev, V. L.; Mao, H. S.; Marcus, M.; Marshall, T.; Mayorov, A. A.; McCroskey, R.; Merekov, Y. P.; Mikhailov, V. A.; Mokhov, N.; Mondal, N. K.; Nagaraj, P.; Narasimham, V. S.; Narayanan, A.; Negret, J. P.; Neustroev, P.; Nozdrin, A. A.; Oshinowo, B.; Parashar, N.; Parua, N.; Podstavkov, V. M.; Polozov, P.; Porokhovoi, S. Y.; Prokhorov, I. K.; Rao, M. V. S.; Raskowski, J.; Reddy, L. V.; Regan, T.; Rotolo, C.; Russakovich, N. A.; Sabirov, B. M.; Satyanarayana, B.; Scheglov, Y.; Schukin, A. A.; Shankar, H. C.; Shishkin, A. A.; Shpakov, D.; Shupe, M.; Simak, V.; Sirotenko, V.; Smith, G.; Smolek, K.; Soustruznik, K.; Stefanik, A.; Steinberg, J.; Stolin, V.; Stoyanova, D. A.; Stutte, L.; Temple, J.; Terentyev, N.; Teterin, V. V.; Tokmenin, V. V.; Tompkins, D.; Uvarov, L.; Uvarov, S.; Vasilyev, I. A.; Vertogradov, L. S.; Vishwanath, P. R.; Vorobyov, A.; Vysotsky, V. B.; Willutzki, H.; Wobisch, M.; Wood, D. R.; Yamada, R.; Yatsunenko, Y. A.; Yoffe, F.; Zanabria, M.; Zhao, T.; Zieminska, D.; Zieminski, A.; Zvyagintsev, S. A.

    2005-11-01

    We describe the design, construction, and performance of the upgraded DØ muon system for Run II of the Fermilab Tevatron collider. Significant improvements have been made to the major subsystems of the DØ muon detector: trigger scintillation counters, tracking detectors, and electronics. The Run II central muon detector has a new scintillation counter system inside the iron toroid and an improved scintillation counter system outside the iron toroid. In the forward region, new scintillation counter and tracking systems have been installed. Extensive shielding has been added in the forward region. A large fraction of the muon system electronics is also new.

  3. Specific light exposure of galactosylated Zn(II) phthalocyanines for selective PDT effects on breast cancer cells

    NASA Astrophysics Data System (ADS)

    Mantareva, V. N.; Kril, A.; Angelov, I.; Avramov, L.

    2013-03-01

    Photodynamic therapy (PDT) is a clinically approved non-invasive and curative procedure for different oncological and non-oncological applications. PDT is still under development due to several limitations which lead to partially successful photodynamic response. The crucial steps in PDT procedure are binding of the photosensitizer to outer cell membrane, its penetration and subcellular localization which envisage the target sites of reactive oxygen species generated during irradiation. Since the surrounding normal cells are also exposed to the photosensitizer and the ambient daylight can be harmful for healthy tissues after therapeutic light application, the challenging task in PDT research is to optimize the procedure in a way to reach tumor cell selectivity. The present study outlines the influence of a light exposure pre-treatment (prior therapeutic light) with specific wavelengths (365 nm and 635 nm) on the uptake, the localization and further re-localization of galactose-substituted Zn(II) phthalocyanines into MDA-MB-231 breast cancer cells. The in vitro photodynamic effect towards tumor cells was studied in comparison to the normal cell line Balb/c 3T3 (clone 31) after pre-irradiation with UV light (365 nm) and red LED (635 nm). The results suggest that the galactose functional groups of Zn(II) phthalocyanine and the harmless UV light at 365 nm favor the selective PDT response.

  4. Photodynamic Therapy (PDT): PDT Mechanisms

    PubMed Central

    Allison, Ron R.

    2013-01-01

    Photodynamic therapy (PDT) is a light based therapy used to ablate tumors. As practiced in oncology a photosensitizing agent is applied and then activated by a specific wavelength and energy of light. This light energy in the presence of oxygen will lead to the creation of the photodynamic reaction which is cyto and vasculo toxic. This paper will review the mechanisms of action of PDT and how they may be manipulated to improve clinical outcome in cancer patients. PMID:23422955

  5. Verteporfin, photofrin II, and merocyanine 540 as PDT photosensitizers against melanoma cells

    SciTech Connect

    Nowak-Sliwinska, Patrycja; Karocki, Andrzej; Elas, Martyna; Pawlak, Anna; Stochel, Grazyna . E-mail: stochel@chemia.uj.edu.pl; Urbanska, Krystyna . E-mail: urbanska@awe.uj.edu.pl

    2006-10-20

    The efficiency of photodynamic effect (PDE) for Photofrin II (PfII), Verteporfin, and Merocyanine 540 (MC540) was compared against neoplastic cells. Triplet state lifetimes and singlet molecular oxygen quantum yields were correlated with biological effect. PfII triplet lifetime was two times longer than that of Verteporfin, however, its singlet molecular oxygen quantum yield was two times lower in comparison with Verteporfin. High singlet molecular oxygen quantum yield of Verteporfin resulted in high biological efficacy. To achieve 50% mortality of cells four times lower light dose and five times lower concentration of Verteporfin were applied in comparison with PfII. The same level of cell damage was reached using 10 times higher light dose and two times higher concentration of MC540 in comparison with PfII. Our results confirm that singlet molecular oxygen based mechanism, prevalent for Verteporfin and PfII, was highly effective against melanoma cells. Verteporfin can be used at small doses with high cellular damage efficiency.

  6. Organometallic Ru(II) Photosensitizers Derived from π-Expansive Cyclometalating Ligands: Surprising Theranostic PDT Effects.

    PubMed

    Sainuddin, Tariq; McCain, Julia; Pinto, Mitch; Yin, Huimin; Gibson, Jordan; Hetu, Marc; McFarland, Sherri A

    2016-01-01

    The purpose of the present study was to investigate the influence of π-expansive cyclometalating ligands on the photophysical and photobiological properties of organometallic Ru(II) compounds. Four compounds with increasing π conjugation on the cyclometalating ligand were prepared, and their structures were confirmed by HPLC, 1D and 2D (1)H NMR, and mass spectrometry. The properties of these compounds differed substantially from their Ru(II) polypyridyl counterparts. Namely, they were characterized by red-shifted absorption, very weak to no room temperature phosphorescence, extremely short phosphorescence state lifetimes (<10 ns), low singlet oxygen quantum yields (0.5-8%), and efficient ligand-centered fluorescence. Three of the metal complexes were very cytotoxic to cancer cells in the dark (EC50 values = 1-2 μM), in agreement with what has traditionally been observed for Ru(II) compounds derived from small C^N ligands. Surprisingly, the complex derived from the most π-expansive cyclometalating ligand exhibited no cytotoxicity in the dark (EC50 > 300 μM) but was phototoxic to cells in the nanomolar regime. Exceptionally large phototherapeutic margins, exceeding 3 orders of magnitude in some cases, were accompanied by bright ligand-centered intracellular fluorescence in cancer cells. Thus, Ru(II) organometallic systems derived from π-expansive cyclometalating ligands, such 4,9,16-triazadibenzo[a,c]napthacene (pbpn), represent the first class of potent light-responsive Ru(II) cyclometalating agents with theranostic potential. PMID:26672769

  7. MUON EDM EXPERIMENT USING STAGE II OF THE NEUTRINO FACTORY.

    SciTech Connect

    FERNOW,R.C.; GALLARDO,J.C.; MORSE,W.M.; SEMERTZIDIS,Y.K.

    2002-07-01

    During the second stage of a future neutrino factory unprecedented numbers of bunched muons will become available. The cooled medium-energy muon beam could be used for a high sensitivity search for an electric dipole moment (EDM) of the muon with a sensitivity better than 10{sup -24}e {center_dot} cm. This will make the sensitivity of the EDM experiment to non-standard physics competitive and in many models more sensitive than the present limits on edms of the electron and nucleons. The experimental design exploits the strong motional electric field sensed by relativistic particles in a magnetic storage ring.

  8. The Performance and Long Term Stability of the D0 Run II Forward Muon Scintillation Counters

    SciTech Connect

    Bezzubov, V.; Denisov, D.; Evdokimov, V.; Lipaev, V.; Shchukin, A.; Vasilyev, I.

    2014-07-21

    The performance of the D0 experiment forward muon scintillation counters system during Run II of the Tevatron from 2001 to 2011 is described. The system consists of 4214 scintillation counters in six layers. The long term stability of the counters amplitude response determined using LED calibration system and muons produced in proton-antiproton collisions is presented. The average signal amplitude for counters of all layers has gradually decreased over ten years by 11%. The reference timing, determined using LED calibration, was stable within 0.26 ns. Average value of muon timing peak position was used for periodic D0 clock signal adjustments to compensate seasonal drift caused by temperature variations. Counters occupancy for different triggers in physics data collection runs and for minimum bias triggers are presented. The single muon yields versus time and the luminosity dependence of yields were stable for the forward muon system within 1% over 10 years.

  9. GPD physics with polarized muon beams at COMPASS-II

    SciTech Connect

    Ferrero, Andrea [CEA-Saclay, DSM Collaboration: COMPASS Collaboration

    2013-04-15

    A major part of the future COMPASS program is dedicated to the investigation of the nucleon structure through Deeply Virtual Compton Scattering (DVCS) and Deeply Virtual Meson Production (DVMP). COMPASS will measure DVCS and DVMP reactions with a high intensity muon beam of 160 GeV and a 2.5 m-long liquid hydrogen target surrounded by a new TOF system. The availability of muon beams with high energy and opposite charge and polarization will allow to access the Compton form factor related to the dominant GPD H and to study the x{sub B}-dependence of the t-slope of the pure DVCS cross section and to study nucleon tomography. Projections on the achievable accuracies and preliminary results of pilot measurements will be presented.

  10. FEASIBILITY STUDY II OF A MUON BASED NEUTRINO SOURCE.

    SciTech Connect

    GALLARDO,J.C.; OZAKI,S.; PALMER,R.B.; ZISMAN,M.

    2001-06-30

    The concept of using a muon storage ring to provide a well characterized beam of muon and electron neutrinos (a Neutrino Factory) has been under study for a number of years now at various laboratories throughout the world. The physics program of a Neutrino Factoryis focused on the relatively unexplored neutrino sector. In conjunction with a detector located a suitable distance from the neutrino source, the facility would make valuable contributions to the study of neutrino masses and lepton mixing. A Neutrino Factory is expected to improve the measurement accuracy of sin{sup 2}(2{theta}{sub 23}) and {Delta}m{sup 2}{sub 32} and provide measurements of sin{sup 2}(2{theta}{sub 13}) and the sign of {Delta}m{sup 2}{sub 32}. It may also be able to measure CP violation in the lepton sector.

  11. PDT: death pathways

    NASA Astrophysics Data System (ADS)

    Kessel, David

    2007-02-01

    Cellular targets of photodynamic therapy include mitochondria, lysosomes, the endoplasmic reticulum (ER) and the plasma membrane. PDT can evoke necrosis, autophagy and apoptosis, or combinations of these, depending on the PDT dose, the site(s) of photodamage and the cellular phenotype. It has been established that loss of viability occurs even when the apoptotic program is inhibited. Studies assessing effects of ER or mitochondrial photodamage, involving loss of Bcl-2 function, indicate that low-dose PDT elicited a rapid autophagic response in L1210 cells. This was attributed to the ability of autophagy to recycle photodamaged organelles, and there was partial protection from loss of viability. This effect was not observed in L1210/Atg7, where autophagy was silenced. At higher PDT doses, apoptotic cells were observed within 60 min in both cell lines, but more so in L1210. The ability of L1210 cells to undergo autophagy did not offer protection from cell death at the higher PDT dose. Previous studies had indicated that autophagy can contribute to cell death, since L1210 cells that do not undergo an initial apoptotic response often contain multiple autophagic vacuoles 24 hr later. With L1210/Atg7, apoptosis alone may account for the loss of viability at an LD 90 PDT dose.

  12. Multiyear search for a diffuse flux of muon neutrinos with AMANDA-II

    NASA Astrophysics Data System (ADS)

    Achterberg, A.; Ackermann, M.; Adams, J.; Ahrens, J.; Andeen, K.; Auffenberg, J.; Bai, X.; Baret, B.; Barwick, S. W.; Bay, R.; Beattie, K.; Becka, T.; Becker, J. K.; Becker, K.-H.; Berghaus, P.; Berley, D.; Bernardini, E.; Bertrand, D.; Besson, D. Z.; Blaufuss, E.; Boersma, D. J.; Bohm, C.; Bolmont, J.; Böser, S.; Botner, O.; Bouchta, A.; Braun, J.; Burgess, T.; Castermans, T.; Chirkin, D.; Christy, B.; Clem, J.; Cowen, D. F.; D'Agostino, M. V.; Davour, A.; Day, C. T.; de Clercq, C.; Demirörs, L.; Descamps, F.; Desiati, P.; De Young, T.; Diaz-Velez, J. C.; Dreyer, J.; Dumm, J. P.; Duvoort, M. R.; Edwards, W. R.; Ehrlich, R.; Eisch, J.; Ellsworth, R. W.; Evenson, P. A.; Fadiran, O.; Fazely, A. R.; Filimonov, K.; Finley, C.; Foerster, M. M.; Fox, B. D.; Franckowiak, A.; Franke, R.; Gaisser, T. K.; Gallagher, J.; Ganugapati, R.; Geenen, H.; Gerhardt, L.; Goldschmidt, A.; Goodman, J. A.; Gozzini, R.; Griesel, T.; Groß, A.; Grullon, S.; Gunasingha, R. M.; Gurtner, M.; Ha, C.; Hallgren, A.; Halzen, F.; Han, K.; Hanson, K.; Hardtke, D.; Hardtke, R.; Hart, J. E.; Hasegawa, Y.; Hauschildt, T.; Hays, D.; Heise, J.; Helbing, K.; Hellwig, M.; Herquet, P.; Hill, G. C.; Hodges, J.; Hoffman, K. D.; Hommez, B.; Hoshina, K.; Hubert, D.; Hughey, B.; Hülß, J.-P.; Hulth, P. O.; Hultqvist, K.; Hundertmark, S.; Inaba, M.; Ishihara, A.; Jacobsen, J.; Japaridze, G. S.; Johansson, H.; Jones, A.; Joseph, J. M.; Kampert, K.-H.; Kappes, A.; Karg, T.; Karle, A.; Kawai, H.; Kelley, J. L.; Kislat, F.; Kitamura, N.; Klein, S. R.; Klepser, S.; Kohnen, G.; Kolanoski, H.; Köpke, L.; Kowalski, M.; Kowarik, T.; Krasberg, M.; Kuehn, K.; Labare, M.; Landsman, H.; Lauer, R.; Leich, H.; Leier, D.; Liubarsky, I.; Lundberg, J.; Lünemann, J.; Madsen, J.; Maruyama, R.; Mase, K.; Matis, H. S.; McCauley, T.; McParland, C. P.; Meli, A.; Messarius, T.; Mészáros, P.; Miyamoto, H.; Mokhtarani, A.; Montaruli, T.; Morey, A.; Morse, R.; Movit, S. M.; Münich, K.; Nahnhauer, R.; Nam, J. W.; Nießen, P.; Nygren, D. R.; Ögelman, H.; Olivas, A.; Patton, S.; Peña-Garay, C.; Pérez de Los Heros, C.; Piegsa, A.; Pieloth, D.; Pohl, A. C.; Porrata, R.; Pretz, J.; Price, P. B.; Przybylski, G. T.; Rawlins, K.; Razzaque, S.; Resconi, E.; Rhode, W.; Ribordy, M.; Rizzo, A.; Robbins, S.; Roth, P.; Rothmaier, F.; Rott, C.; Rutledge, D.; Ryckbosch, D.; Sander, H.-G.; Sarkar, S.; Satalecka, K.; Schlenstedt, S.; Schmidt, T.; Schneider, D.; Seckel, D.; Semburg, B.; Seo, S. H.; Sestayo, Y.; Seunarine, S.; Silvestri, A.; Smith, A. J.; Solarz, M.; Song, C.; Sopher, J. E.; Spiczak, G. M.; Spiering, C.; Stamatikos, M.; Stanev, T.; Stezelberger, T.; Stokstad, R. G.; Stoufer, M. C.; Stoyanov, S.; Strahler, E. A.; Straszheim, T.; Sulanke, K.-H.; Sullivan, G. W.; Sumner, T. J.; Taboada, I.; Tarasova, O.; Tepe, A.; Thollander, L.; Tilav, S.; Tluczykont, M.; Toale, P. A.; Tosi, D.; Turčan, D.; van Eijndhoven, N.; Vandenbroucke, J.; van Overloop, A.; Viscomi, V.; Voigt, B.; Wagner, W.; Walck, C.; Waldmann, H.; Walter, M.; Wang, Y.-R.; Wendt, C.; Wiebusch, C. H.; Wiedemann, C.; Wikström, G.; Williams, D. R.; Wischnewski, R.; Wissing, H.; Woschnagg, K.; Xu, X. W.; Yodh, G.; Yoshida, S.; Zornoza, J. D.

    2007-08-01

    A search for TeV-PeV muon neutrinos from unresolved sources was performed on AMANDA-II data collected between 2000 and 2003 with an equivalent live time of 807 days. This diffuse analysis sought to find an extraterrestrial neutrino flux from sources with nonthermal components. The signal is expected to have a harder spectrum than the atmospheric muon and neutrino backgrounds. Since no excess of events was seen in the data over the expected background, an upper limit of E2Φ90%C.L.<7.4×10-8GeVcm-2s-1sr-1 is placed on the diffuse flux of muon neutrinos with a Φ∝E-2 spectrum in the energy range 16 TeV to 2.5 PeV. This is currently the most sensitive Φ∝E-2 diffuse astrophysical neutrino limit. We also set upper limits for astrophysical and prompt neutrino models, all of which have spectra different from Φ∝E-2.

  13. Multi-year search for a diffuse flxu of muon neutrinos with AMANDA-II

    SciTech Connect

    IceCube Collaboration; Klein, Spencer; Achterberg, A.; Collaboration, IceCube

    2008-04-13

    A search for TeV-PeV muon neutrinos from unresolved sources was performed on AMANDA-II data collected between 2000 and 2003 with an equivalent livetime of 807 days. This diffuse analysis sought to find an extraterrestrial neutrino flux from sources with non-thermal components. The signal is expected to have a harder spectrum than the atmospheric muon and neutrino backgrounds. Since no excess of events was seen in the data over the expected background, an upper limit of E{sup 2}{Phi}{sub 90%C.L.} < 7.4 x 10{sup -8} GeV cm{sup -2} s{sup -1} sr{sup -1} is placed on the diffuse flux of muon neutrinos with a {Phi} {proportional_to} E{sup -2} spectrum in the energy range 16 TeV to 2.5 PeV. This is currently the most sensitive {Phi} {proportional_to} E{sup -2} diffuse astrophysical neutrino limit. We also set upper limits for astrophysical and prompt neutrino models, all of which have spectra different than {Phi} {proportional_to} E{sup -2}.

  14. Prostate PDT dosimetry

    PubMed Central

    Zhu, Timothy C.; Finlay, Jarod C.

    2015-01-01

    Summary We provide a review of the current state of dosimetry in prostate photodynamic therapy (PDT). PDT of the human prostate has been performed with a number of different photosensitizers and with a variety of dosimetry schemes. The simplest clinical light dose prescription is to quantify the total light energy emitted per length (J/cm) of cylindrical diffusing fibers (CDF) for patients treated with a defined photosensitizer injection per body weight. However, this approach does not take into account the light scattering by tissue and usually underestimates the local light fluence rate, and consequently the fluence. Techniques have been developed to characterize tissue optical properties and light fluence rates in vivo using interstitial measurements during prostate PDT. Optical methods have been developed to characterize tissue absorption and scattering spectra, which in turn provide information about tissue oxygenation and drug concentration. Fluorescence techniques can be used to quantify drug concentrations and photobleaching rates of photosensitizers. PMID:25046988

  15. Synthesis, DNA interactions and antibacterial PDT of Cu(II) complexes of phenanthroline based photosensitizers via singlet oxygen generation

    NASA Astrophysics Data System (ADS)

    Sudhamani, C. N.; Bhojya Naik, H. S.; Sangeetha Gowda, K. R.; Giridhar, M.; Girija, D.; Prashanth Kumar, P. N.

    2015-03-01

    Cu(II) complexes [Cu(mqt)(B)H2O]ClO4(1-3) of 2-thiol 4-methylquinoline and phenanthroline bases (B), viz 1,10-phenanthroline (phen in 1), Dipyrido[3,2-d:2‧,3‧-f]quinoxaline (dpq in 2) and Dipyrido[3,2-a:2‧,3‧-c]phenazine (dppz in 3) have been prepared and characterized by elemental analysis, IR, UV-Vis, magnetic moment values, EPR spectra and conductivity measurements. The spectral data reveal that all the complexes exhibit square-pyramidal geometry. The DNA-binding behaviors of the three complexes were investigated by absorption spectra, viscosity measurements and thermal denaturation studies. The DNA binding constants for complexes (1), (2) and (3) were determined to 2.2 × 103, 1.3 × 104 and 8.6 × 104 M-1 respectively. The experimental results suggest that these complexes interact with DNA through groove-binding mode. The photo induced cleavage studies shows that the complexes possess photonuclease property against pUC19 DNA under UV-Visible irradiation via a mechanistic pathway involving formation of singlet oxygen as the reactive species. Antimicrobial photodynamic therapy was studied using photodynamic antimicrobial chemotherapy (PACT) assay against Escherichiacoli and all complexes exhibited significant reduction in bacterial growth on photoirradiation.

  16. Synthesis, DNA interactions and antibacterial PDT of Cu(II) complexes of phenanthroline based photosensitizers via singlet oxygen generation.

    PubMed

    Sudhamani, C N; Bhojya Naik, H S; Sangeetha Gowda, K R; Giridhar, M; Girija, D; Prashanth Kumar, P N

    2015-03-01

    Cu(II) complexes [Cu(mqt)(B)H2O]ClO4(1-3) of 2-thiol 4-methylquinoline and phenanthroline bases (B), viz 1,10-phenanthroline (phen in 1), Dipyrido[3,2-d:2',3'-f]quinoxaline (dpq in 2) and Dipyrido[3,2-a:2',3'-c]phenazine (dppz in 3) have been prepared and characterized by elemental analysis, IR, UV-Vis, magnetic moment values, EPR spectra and conductivity measurements. The spectral data reveal that all the complexes exhibit square-pyramidal geometry. The DNA-binding behaviors of the three complexes were investigated by absorption spectra, viscosity measurements and thermal denaturation studies. The DNA binding constants for complexes (1), (2) and (3) were determined to 2.2×10(3), 1.3×10(4) and 8.6×10(4)M(-1) respectively. The experimental results suggest that these complexes interact with DNA through groove-binding mode. The photo induced cleavage studies shows that the complexes possess photonuclease property against pUC19 DNA under UV-Visible irradiation via a mechanistic pathway involving formation of singlet oxygen as the reactive species. Antimicrobial photodynamic therapy was studied using photodynamic antimicrobial chemotherapy (PACT) assay against Escherichiacoli and all complexes exhibited significant reduction in bacterial growth on photoirradiation. PMID:25544194

  17. Endoscopic photodynamic therapy (PDT) for oesophageal cancer.

    PubMed

    Moghissi, Keyvan

    2006-06-01

    Endoscopic photodynamic therapy (PDT) is undertaken only when tumour is visible endoscopically with malignancy biopsy confirmed. Patients will be either Group A: inoperable cases with locally advanced cancer when the aim is palliation of dysphagia, or Group E: patients with early stage I-II disease who are unsuitable for surgery or decline operation, when the intent is curative. Following assessment for suitability for PDT and counselling, Photofrin 2mg/(kgbw) is administered 24-72h before endoscopic illumination using a Diode 630nm laser. Illumination may be either interstitial or intraluminal at a dose of 100-200J/cm. PMID:25049097

  18. PDT - PARTICLE DISPLACEMENT TRACKING SOFTWARE

    NASA Technical Reports Server (NTRS)

    Wernet, M. P.

    1994-01-01

    multiple frequency RGB monitor (EGA or better), a math co-processor, and a pointing device. The printers supported by the graphical analysis routines are the HP Laserjet+, Series II, and Series III with at least 1.5 MB memory. The data acquisition routines require the EPIX 4-MEG video board and optional 12.5MHz oscillator, and associated EPIX software. Data can be acquired from any CCD or RS-170 compatible video camera with pixel resolution of 600hX400v or better. PDT is distributed on one 5.25 inch 360K MS-DOS format diskette. Due to the use of required proprietary software, executable code is not provided on the distribution media. Compiling the source code requires the Microsoft C v5.1 compiler, Microsoft QuickC v2.0, the Microsoft Mouse Library, EPIX Image Processing Libraries, the Microway NDP-Fortran-386 v2.1 compiler, and the Media Cybernetics HALO Professional Graphics Kernal System. Due to the complexities of the machine requirements, COSMIC strongly recommends the purchase and review of the documentation prior to the purchase of the program. The source code, and sample input and output files are provided in PKZIP format; the PKUNZIP utility is included. PDT was developed in 1990. All trade names used are the property of their respective corporate owners.

  19. DUMAND-II (deep underwater muon and neutrino detector) progress report

    SciTech Connect

    Young, K.K.; The DUMAND Collaboration

    1995-07-10

    The DUMAND II detector will search for astronomical sources of high energy neutrinos. Successful deployment of the basic infrastructure, including the shore cable, the underwater junction box, and an environmental module was accomplished in December, 1993. One optical module string was also deployed and operated, logging data for about 10 hours. The underwater cable was connected to the shore station where we were able to successfully exercise system controls and log further environmental data. After this time, water leaking into the electronics control module for the deployed string disabled the string electrical system. The acquired data are consistent with the expected rate of downgoing muons, and our ability to reconstruct muons was demonstrated. The measured acoustical backgrounds are consistent with expectation, which should allow acoustical detection of nearby PeV particle cascades. The disabled string has been recovered and is undergoing repairs ashore. We have identified the source of the water leak and implemented additional testing and QC procedures to ensure no repetition in our next deployment. We will be ready to deploy three strings and begin continuous data taking in late 1994 or early 1995. {copyright} {ital 1995} {ital American} {ital Institute} {ital of} {ital Physics}.

  20. Effects of HSP27 downregulation on PDT resistance through PDT-induced autophagy in head and neck cancer cells.

    PubMed

    Kim, Jisun; Lim, Haesoon; Kim, Sangwoo; Cho, Hyejung; Kim, Yong; Li, Xiaojie; Choi, Hongran; Kim, Okjoon

    2016-04-01

    We previously reported that photodynamic therapy (PDT) induces cell death in head and neck cancer through both autophagy and apoptosis. Regulation of cell death by autophagy and apoptosis is important to enhance the effects of PDT. Autophagy maintains a balance between cell death and PDT resistance. Downregulation of heat shock protein 27 (HSP27) induces PDT resistance in head and neck cancer cells. Furthermore, HSP70 regulates apoptosis during oxidative stress. However, the role of HSPs in PDT-induced cell death through autophagy and apoptosis is unclear. Therefore, in the present study, we investigated the effects of HSP27 and HSP70 on PDT-induced cell death of oral cancer cells through autophagy and apoptosis. Cancer cells were treated with hematoporphyrin at varying doses, followed by irradiation at 635 nm with an energy density of 5 mW/cm2. We determined the changes in HSP expression by determining the levels of PARP-1 and LC3II in PDT-resistant cells. Furthermore, we assessed cell death signaling after downregulating HSPs by transfecting specific siRNAs. We observed that PDT decreased HSP27 expression but increased HSP70 expression in the head and neck cancer cells. Treatment of cells with LC3II and PARP-1 inhibitors resulted in upregulation of HSP70 and HSP27 expression, respectively. Downregulation of HSP27 and HSP70 induced cell death and PDT resistance through autophagy and apoptosis. Moreover, downregulation of HSP27 in PDT-resistant cells resulted in enhanced survival. These results indicate that the regulation of HSP27 and HSP70 plays a principal role in increasing the effects of PDT by inducing autophagic and apoptotic cell death. PMID:26820233

  1. In vivo light dosimetry for pleural PDT

    NASA Astrophysics Data System (ADS)

    Dimofte, Andreea; Zhu, Timothy C.; Finlay, Jarod C.; Culligan, Melissa; Edmonds, Christine E.; Friedberg, Joseph S.; Cengel, Keith; Hahn, Stephen M.

    2009-02-01

    In-vivo light Dosimetry for patients undergoing photodynamic therapy (PDT) is one of the important dosimetry quantities critical for predicting PDT outcome. This study examines the light fluence (rate) delivered to patients undergoing pleural PDT as a function of treatment time, treatment volume and surface area, and its accuracy as a function of the calibration accuracies of each isotropic detector and the calibration integrating sphere. The patients studied here were enrolled in Phase II clinical trial of Photofrin-mediated PDT for the treatment of non-small cell lung cancer with pleural effusion. The ages of the patients studied varied from 34 to 69 year old. All patients were administered 2mg per kg body weight Photoprin 24 hours before the surgery. Patients undergoing photodynamic therapy (PDT) are treated with laser light with a light fluence of 60 J/cm^2 at 630nm. Fluence rate (mW/cm^2) and cumulative fluence (J/cm^2) was monitored at 7 different sites during the entire light treatment delivery. Isotropic detectors were used for in-vivo light dosimetry. The anisotropy of each isotropic detector was found to be within 30%. The mean fluence rate delivery varied from 37.84 to 94.05 mW/cm^2 and treatment time varied from 1762 to 5232s. We have established a correlation between the treatment time and the treatment volume. The results are discussed using an integrating sphere theory and the measured tissue optical properties. The result can be used as a clinical guideline for future pleural PDT treatment.

  2. Measurement of the Flux and Zenith-Angle Distribution of Upward Through-Going Muons in Kamiokande II+III

    NASA Astrophysics Data System (ADS)

    Hatakeyama, S.; Hara, T.; Fukuda, Y.; Hayakawa, T.; Inoue, K.; Ishihara, K.; Ishino, H.; Joukou, S.; Kajita, T.; Kasuga, S.; Koshio, Y.; Kumita, T.; Matsumoto, K.; Nakahata, M.; Nakamura, K.; Okumura, K.; Sakai, A.; Shiozawa, M.; Suzuki, J.; Suzuki, Y.; Tomoeda, T.; Totsuka, Y.; Hirata, K. S.; Kihara, K.; Oyama, Y.; Koshiba, M.; Nishijima, K.; Horiuchi, T.; Fujita, K.; Koga, M.; Maruyama, T.; Suzuki, A.; Mori, M.; Suda, T.; Suzuki, A. T.; Ishizuka, T.; Miyano, K.; Okazawa, H.; Nagashima, Y.; Takita, M.; Yamaguchi, T.; Hayato, Y.; Kaneyuki, K.; Suzuki, T.; Takeuchi, Y.; Tanimori, T.; Tasaka, S.; Ichihara, E.; Miyamoto, S.; Nishikawa, K.

    1998-09-01

    The flux of upward through-going muons of minimum (mean) threshold energy >1.6 (3.0) GeV is measured, based on a total of 372 events observed by the Kamiokande II+III detector during 2456 detector live days. The observed muon flux was Φobs = [1.94+/-0.10\\(stat.\\)+0.07-0.06sys.\\)]×10-13 cm-2 s-1 sr-1, which is compared to an expected value of Φtheo = [2.46+/-0.54\\(theo.\\)]×10-13 cm-2 s-1 sr-1. The observation is in agreement with the prediction within the errors. The zenith-angle dependence of the observed upward through-going muons supports the previous indication of neutrino oscillations made by Kamiokande using sub- and multi-GeV atmospheric neutrino events.

  3. Photodynamic therapy (PDT) for perianal bowenoid papulosis

    NASA Astrophysics Data System (ADS)

    Gahlen, Johannes; Stern, Josef; Graschew, Georgi; Kaus, Michael R.; Tilgen, W.

    1995-03-01

    HPV associated bowenoid papulosis of the anogenital region are classified as carcinoma in situ. The treatment can be difficult and recurrence rates are high. Extended surgical resections may have complications such as anal sphincter insufficiency. PDT does have some advantages and less side effects in the treatment of these tumors. We treated one female patient with an extended perianal bowenoid papulosis. Previous surgical resection led to local recurrence and partial sphincter insufficiency. Twenty-four hours before local laser light radiation (Ar-Dye laser, 630 nm wavelength), a systemic photosensitizer was applied (Photofrin II, 1.5 mg/kg BW). Four courses of PDT were performed within one year. We observed a total tumor necrosis in every radiation area. The previous sphincter insufficiency improved during the sessions. Side effects were rare. Pain in the radiation was stopped within 2 - 3 days under pain medication. PDT can induce a total local tumor necrosis in perianal bowenoid papulosis. Concerning local expansion, PDT can be a curable treatment.

  4. Atomic effects in tritium beta-decay. II. Muon to electron conversion in atoms

    SciTech Connect

    Wampler, K.D.

    1989-01-01

    I. The final-state, atomic effects in the low energy end of the tritium beta decay spectrum are studied in detail. The author treats the instantaneous, two-electron repulsion in the final state, effectively to all orders in perturbation theory, by solving the eigenvalue problem with a discretized and truncated form of the Hamiltonian. He finds that these effects fail to explain the distortion in the spectrum observed by Simpson (Phys. Rev. Lett. 54, 649 (1985)). Simpson attributed this distortion to the admixture of a heavy mass antineutrino in the outgoing electron antineutrino state. In fact, the final-state Coulomb effects enhance the distortion. This calculation clears up some of the ambiguities of other theoretical analyses based on considerations of screening functions and perturbation theory. II. He presents a phenomenological study of separate lepton number violating muon to electron conversion in atoms. Previous work on this process has concentrated on elastic transitions where the nucleus characteristics have the gate on the substrate and the source-drain contacts on the top of the sample. The first use as an FET dielectric is reported of hydrogenated amorphous silicon-carbon (prepared from silane and propane mixture), photo-oxidised by UV lamp or laser. These FETs have similar characteristics to those with silicon nitride gate insulator but without the difficulties of preparing good insulator/semiconductor interfaces. Using the same materials attempts have been made to produce charge coupled devices.

  5. PDT: What's Past Is Prologue.

    PubMed

    Cengel, Keith A; Simone, Charles B; Glatstein, Eli

    2016-05-01

    Despite descriptions of light-mediated therapy in ancient texts and the discovery of photodynamic therapy (PDT) in the early 1900s, the landmark article in 1978 in Cancer Research by Dougherty and his colleagues at the Roswell Park Cancer Institute remains rightly viewed as the starting point for clinical PDT in modern medicine. As a large clinical series that explored many of the factors now viewed as critical determinates of PDT dose, efficacy, and toxicity, that study showed remarkable foresight, yet it also served to raise as many questions as it answered. Since its publication, PDT has been increasingly utilized in clinical practice for the treatment of both benign and malignant conditions, and many of their questions have yielded new technologies and areas of investigation, thus remaining highly relevant nearly 40 years after their initial asking. Moreover, continuing advances in our ability to measure physical properties such as absorbed light dose, photosensitizer concentration, tissue oxygen concentration, and singlet oxygen production in real-time may allow for adaptive modification of light delivery during PDT on a fine scale to optimize treatment response. Finally, combining molecularly targeted drugs and novel photosensitizers has the potential to improve further the therapeutic index and extend the spectrum of clinical PDT far beyond what was imagined when that sentinel manuscript was written. Cancer Res; 76(9); 2497-9. ©2016 AACRSee related article by Dougherty et al., Cancer Res 1978;38:2628-35Visit the Cancer Research 75(th) Anniversary timeline. PMID:27197260

  6. A Diffusion Cloud Chamber Study of Very Slow Mesons. II. Beta Decay of the Muon

    DOE R&D Accomplishments Database

    Lederman, L. M.; Sargent, C. P.; Rinehart, M.; Rogers, K.

    1955-03-01

    The spectrum of electrons arising from the decay of the negative mu meson has been determined. The muons are arrested in the gas of a high pressure hydrogen filled diffusion cloud chamber. The momenta of the decay electrons are determined from their curvature in a magnetic field of 7750 gauss. The spectrum of 415 electrons has been analyzed according to the theory of Michel.

  7. Photodynamic therapy (PDT) for locally recurrent breast carcinoma

    NASA Astrophysics Data System (ADS)

    Gahlen, Johannes; Stern, Josef; Graschew, Georgi; Kaus, Michael R.; Herfarth, Christian

    1995-03-01

    Locally recurrent breast carcinoma and skin metastasisses on the chest wall can be difficult to treat. Conventional treatments like radiation-, chemo- and hormonal therapy have shown poor results in these patients. In comparison to this, PDT has some advantages and less side effects. We can observe a tumor accumulation of a systemic applied photosensitizer (PS). The PS can be stimulated by light of a wavelength of 630 nm and a phototoxic effect in the tumor occurs. We treated 7 patients with locally recurrent breast carcinoma 15 times with PDT. The intravenous application of the PS (Photofrin II, 1.5 mg/kg BW) was done 24 - 96 hours before local laser light radiation. The light source was an Ar-Dye laser with a wavelength of 630 nm. Due to a local tumor necrosis we observed a tumor reduction in each case. In 5 patients we saw a complete local remission with a good cosmetic result. Side effects were rare. All patients suffered from pain in the treated area. No major phototoxicity effects were seen. PDT can induce complete local tumor remissions in patients with cutaneous metastasisses after locally recurrent breast carcinoma. In absence of other metastasisses PDT is possibly a curative treatment. One of the major advantages of this treatment are the rare side effects, rare complications and the possible repetition of the PDT.

  8. In-vivo outcome study of HPPH mediated PDT using singlet oxygen explicit dosimetry (SOED)

    NASA Astrophysics Data System (ADS)

    Penjweini, Rozhin; Kim, Michele M.; Zhu, Timothy C.

    2015-03-01

    Type II photodynamic therapy (PDT) is based on the use of photochemical reactions mediated through an interaction between a tumor-selective photosensitizer, photoexcitation with a specific wavelength of light, and production of reactive singlet oxygen. However, the medical application of this technique has been limited due to inaccurate PDT dosimetric methods. The goal of this study is to examine the relationship between outcome (in terms of tumor growth rate) and calculated reacted singlet oxygen concentration [1O2]rx after HPPH-mediated PDT to compare with other PDT dose metrics, such as PDT dose or total light fluence. Mice with radiation-induced fibrosarcoma (RIF) tumors were treated with different light fluence and fluence rate conditions. Explicit measurements of photosensitizer drug concentration and tissue optical properties via fluorescence and absorption measurement with a contact probe before and after PDT were taken to then quantify total light fluence, PDT dose, and [1O2]rx based on a macroscopic model of singlet oxygen. In addition, photobleaching of photosenitizer were measured during PDT as a second check of the model. Changes in tumor volume were tracked following treatment and compared to the three calculated dose metrics. The correlations between total light fluence, PDT dose, reacted [1O2]rx and tumor growth demonstrate that [1O2]rx serves as a better dosimetric quantity for predicting treatment outcome and a clinically relevant tumor growth endpoint.

  9. Photodynamic therapy (PDT) as a biological modifier

    NASA Astrophysics Data System (ADS)

    Obochi, Modestus; Tao, Jing-Song; Hunt, David W. C.; Levy, Julia G.

    1996-04-01

    The capacity of photosensitizers and light to ablate cancerous tissues and unwanted neovasculature constitutes the classical application of photodynamic therapy (PDT). Cell death results from either necrotic or apoptotic processes. The use of photosensitizers and light at doses which do not cause death has been found to affect changes in certain cell populations which profoundly effect their expression of cell surface molecules and secretion of cytokines, thereby altering the functional attributes of the treated cells. Cells of the immune system and the skin may be sensitive to modulation by 'sub-lethal PDT.' Ongoing studies have been conducted to assess, at the molecular level, changes in both lymphocytes and epidermal cells (EC) caused by treatment with low levels of benzoporphyrin derivative monoacid ring A (BPD) (a photosensitizer currently in clinical trials for cancer, psoriasis, endometriosis and age-related macular degeneration) and light. Treatment of skin with BPD and light, at levels which significantly enhanced the length of murine skin allograft acceptance, have been found to down-regulate the expression of Langerhans cell (LC) surface antigen molecules [major histocompatibility complex (MHC) class II and intracellular adhesion molecule (ICAM)-1] and the formation of some cytokines (tumor necrosis factor-alpha (TNF- (alpha) ).

  10. Apoptotic effects of Photofrin-Diomed 630-PDT on SHEEC human esophageal squamous cancer cells

    PubMed Central

    Gao, Shegan; Zhang, Mengxi; Zhu, Xiaojuan; Qu, Zhifeng; Shan, Tanyou; Xie, Xuanhu; Wang, Ying; Feng, Xiaoshan

    2015-01-01

    Photodynamic therapy (PDT) using photofrin-II is a clinically effective treatment for both non-neoplastic and neoplastic diseases. Herein, we performed an in vitro experiment to study the anti-tumor effect and mechanisms of photofrin-II mediated PDT for esophageal squamous cell carcinoma (ESCC) cell line, SHEEC. In this study, human ESCC cell line SHEEC and parental normal cell line SHEE were used. The anti-tumor effect of PDT was determined by evaluating cell viability using CCK-8 assay, apoptosis and generation of reactive oxygen species (ROS). PDT induced significant apoptosis in SHEEC and SHEE cells in a time- and photofrin-II dose-dependent manner. Furthermore, PDT treatment induced significant death of SHEEC, instead of SHEE cells. The apoptotic outcome was accompanied by concurrent generation of ROS. In summary, PDT shed light on therapy of ESCC, functioning as a useful tool for ESCC clinical treatment, providing a better understanding of Photofrin-Diomed 630-PDT in SHEEC cells. PMID:26628993

  11. The role of DAMPS in ALA-PDT for skin squamous cell carcinoma (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Wang, Xiuli; Wang, Xiaojie; Ji, Jie; Zhang, Haiyan; Shi, Lei

    2016-03-01

    5-Aminolevulinic acid mediated photodynamic therapy (ALA-PDT) is an established local approach for skin squamous cell carcinoma. It is believed that dangerous signals damage-associated molecular patterns (DAMPs) play an important role in ALA-PDT. In this study, we evaluated in vitro and in vivo expressions of major DAMPs, calreticulin (CRT), heat shock proteins 70 (HSP70), and high mobility group box 1 (HMGB1), induced by ALA-PDT using immunohistochemistry, western blot, and ELISA in a squamous cell carcinoma (SCC) mouse model. The role of DAMPs in the maturation of DCs potentiated by ALA-PDT-treated tumor cells was detected by FACS and ELISA. Our results showed that ALA-PDT enhanced the expression of CRT, HSP70, and HMGB1. These induced DAMPs played an important role in activating DCs by PDT-treated tumor cells, including phenotypic maturation (upregulation of surface expression of MHC-II, CD80, and CD86) and functional maturation (enhanced capability to secrete IFN-γ and IL-12). Furthermore, injecting ALA-PDT-treated tumor cells into naïve mice resulted in complete protection against cancer cells of the same origin. Our findings indicate that ALA-PDT can upregulate DAMPs and enhance tumor immunogenicity, providing a promising strategy for inducing a systemic anticancer immune response.

  12. Optical molecular imaging in PDT

    NASA Astrophysics Data System (ADS)

    Mitra, Soumya; Snyder, John W.; Foster, Thomas H.

    2007-02-01

    Motivated by recent successes in fluorescence imaging of whole mount tissue preparations and by rapid progress in the fields of molecular imaging and molecular biology, we are exploring a number of applications of optical fluorescence imaging in superficial murine tumor models in vivo. Imaging the PDT-induced expression of the heat shock protein 70 (HSP70) in cells and in vivo is accomplished using stably transfected EMT6 cells in which the gene for GFP is under the control of the HSP70 promoter. These cells readily form solid tumors in BALB/c mice, enabling the direct imaging of the extent and time course of the activation of this promoter, with each mouse serving as its own control. Imaging of similarly transfected EMT6 cells with a HIF-1α/GFP fusion protein vector enables visualization of HIF-1α translocation to the nucleus. Recently, we have accomplished fluorescent labeling of surface antigens in vivo using intratumor and intravenous injection of fluorophore-conjugated antibodies. Injection of deep-red fluorophore-conjugated-anti-CD31 enables confocal fluorescence imaging of the tumor vasculature to depths of at least 100 microns. With the vessels rendered fluorescent in this way, a number of interesting studies become possible in the living mouse, including the direct visualization of photosensitizer distribution from perfused vessels. Using the appropriate fluorophore-conjugated antibodies, we have also been able to image infiltrating granulocytes in EMT6 tumors in response to PDT in vivo.

  13. ALA-PDT mediated DC vaccine for skin squamous cell carcinoma

    NASA Astrophysics Data System (ADS)

    Ji, Jie; Fan, Zhixia; Zhou, Feifan; Wang, Xiaojie; Shi, Lei; Zhang, Haiyan; Wang, Peiru; Yang, Degang; Zhang, Linglin; Wang, Xiuli; Chen, Wei R.

    2015-03-01

    Dendritic cell (DC) based vaccine has emerged as a promising immunotherapy for cancers. However, most DC vaccines so far have only achieved limited success in cancer treatment. Photodynamic therapy (PDT), an established cancer treatment strategy, can cause immunogenic apoptosis to induce an effective antitumor immune response. In this study, we developed a DC-based cancer vaccine using immunogenic apoptotic tumor cells induced by 5-aminolevulinic acid (ALA) mediated PDT. The maturation of DCs induced by PDT-treated apoptotic cells was evaluated. The anti-tumor immunity of ALA-PDT-DC vaccine was tested with mouse model. We observed the maturations of DCs potentiated by ALA-PDT treated tumor cells, including phenotypic maturation (upregulation of surface expression of MHC-II, DC80, and CD86), and functional maturation (enhanced capability to secret INF-Υ and IL-12). ALA-PDT-DC vaccine mediated by apoptotic cells provided protection against tumor in mice, far stronger than that of DC vaccine obtained from freeze/thaw treated tumor cells. Our results indicate that immunogenic apoptotic tumor cells can be more effective in enhancing DC-based cancer vaccine, which could improve the clinical application of PDT- DC vaccines.

  14. Naphthalocyanine-complexes as potential photosensitizers for PDT of tumors

    NASA Astrophysics Data System (ADS)

    Shopova, Maria; Woehrle, Dieter; Mantareva, Vanya; Mueller, Silke

    1999-07-01

    In the present paper information about the synthesis and results on the pharmacokinetic and experimental photodynamic therapy (PDT) of naphthalocyanines are given. The photodynamic activity of differently substituted zinc(II)- and silicon(IV)-naphthalocyanines using liposomes or Cremophor EL as drug-delivery systems is shown on different tumor models. For the evaluation of the phototherapeutic effect different assessment criteria were used, including light and electron microscope observations. The main conclusions which can be arrived at on the basis of our findings are the following: silicon(IV)-naphthalocyanine seems to be not a very effective tumor sensitizer, especially in the treatment o pigmented melanoma, while zinc(II)-naphthalocyanines appear to be very promising for PDT of tumors. Their selective targeting and slow clearance from tumor tissue, fast clearance from skin and pronounced phototherapeutic effect on different tumor models and especially at melanotic tumors, even after application of low drug doses, make this group of photosensitizers very attractive for successful PDT of cancer.

  15. Stimulation of dendritic cells by DAMPs in ALA-PDT treated SCC tumor cells

    PubMed Central

    Zhang, Haiyan; Fan, Zhixia; Zhang, Linglin; Shi, Lei; Zhou, Feifan; Chen, Wei R.; Wang, Hongwei; Wang, Xiuli

    2015-01-01

    Photodynamic therapy (PDT) not only kills tumor cells directly but also rapidly recruits and activates immune cells favoring the development of antitumor adaptive immunity. It is believed that Topical 5-aminolevulinic acid mediated photodynamic therapy (ALA-PDT) can induce anti-tumor immune responses through dangerous signals damage-associated molecular patterns (DAMPs). In this study, we investigated the effect of ALA-PDT induced DAMPs on immune cells. We focused on the stimulation of dendritic cells by major DAMPs, enhanced the expression of calreticulin (CRT), heat shock proteins 70 (HSP70), and high mobility group box 1 (HMGB1), either individually or in combination. We evaluated in vitro and in vivo expressions of DAMPs induced by ALA-PDT using immunohistochemistry, western blot, and ELISA in a squamous cell carcinoma (SCC) mouse model. The role of DAMPs in the maturation of DCs potentiated by ALA-PDT-treated tumor cells was detected by FACS and ELISA. Our results showed that ALA-PDT enhanced the expression of CRT, HSP70, and HMGB1. These induced DAMPs played an important part in activating DCs by PDT-treated tumor cells, including phenotypic maturation (increase of surface expression of MHC-II, CD80, and CD86) and functional maturation (enhanced capability to secrete IFN-γ and IL-12). Furthermore, injecting ALA-PDT-treated tumor cells into naïve mice resulted in complete protection against cancer cells of the same origin. Our findings indicate that ALA-PDT can increase DAMPs and enhance tumor immunogenicity, providing a promising strategy for inducing a systemic anticancer immune response. PMID:26625309

  16. Photosensitizer dosimetry controlled PDT treatment planning reduces inter-individual variability in response to PDT

    NASA Astrophysics Data System (ADS)

    Zhou, Xiaodong; Pogue, Brian W.; Chen, Bin; Demidenko, Eugene; Joshi, Rohan; Hoopes, Jack; Hasan, Tayyaba

    2006-02-01

    Effective Photodynamic therapy (PDT) treatment depends on the amount of active photosensitizer and the delivered light in the targeting tissue. For the same PDT treatment protocol, variation in photosensitizer uptake between animals induces variation in the treatment response between animals. This variation can be compensated via control of delivered light dose through photodynamic dose escalation based on online dosimetry of photosensitizer in the animal. The subcutaneous MAT-LyLu Dunning prostate tumor model was used in this study. Photosensitizer BPD-MA uptake was quantified by multiple fluorescence micro-probe measurements at 3 hours after verteporfin administration. PDT irradiation was carried out after photosensitizer uptake measurement with a total light dose of 75 J/cm2 and a light dose rate of 50 mW/cm2. Therapeutic response of PDT treatments was evaluated by the tumor regrowth assay. Verteporfin uptake varied considerably among tumors (inter-tumor variation 56% standard deviation) and within a tumor (largest intra-tumor variation 64%). An inverse correlation was found between mean photosensitizer intensity and PDT treatment effectiveness (R2 = 37.3%, p < 0.005). In order to compensate individual PDT treatments, photodynamic doses were calculated on an individual animal basis, by matching the light delivered to provide an equal photosensitizer dose multiplied by light dose. This was completed for the lower-quartile, mean and upper-quartile of the photosensitizer distribution. The coefficient of variance in the surviving fraction decreased from 24.9% in non-compensated PDT (NC-PDT) treatments to 16.0%, 14.0% and 15.9% in groups compensated to the lower-quartile (CL-PDT), the median (CM-PDT) and the upper-quartile (CU-PDT), respectively. In terms of treatment efficacy, the CL-PDT group was significantly less effective compared with NC-PDT, CM-PDT and CU-PDT treatments (p < 0.005). No significant difference in effectiveness was observed between NC-PDT, CM-PDT

  17. Targeted PDT agent eradicates TrkC expressing tumors via photodynamic therapy (PDT).

    PubMed

    Kue, Chin Siang; Kamkaew, Anyanee; Lee, Hong Boon; Chung, Lip Yong; Kiew, Lik Voon; Burgess, Kevin

    2015-01-01

    This contribution features a small molecule that binds TrkC (tropomyosin receptor kinase C) receptor that tends to be overexpressed in metastatic breast cancer cells but not in other breast cancer cells. A sensitizer for (1)O2 production conjugated to this structure gives 1-PDT for photodynamic therapy. Isomeric 2-PDT does not bind TrkC and was used as a control throughout; similarly, TrkC- cancer cells were used to calibrate enhanced killing of TrkC+ cells. Ex vivo, 1- and 2-PDT where only cytotoxic when illuminated, and 1-PDT, gave higher cell death for TrkC+ breast cancer cells. A 1 h administration-to-illumination delay gave optimal TrkC+/TrkC--photocytotoxicity, and distribution studies showed the same delay was appropriate in vivo. In Balb/c mice, a maximum tolerated dose of 20 mg/kg was determined for 1-PDT. 1- and 2-PDT (single, 2 or 10 mg/kg doses and one illumination, throughout) had similar effects on implanted TrkC- tumors, and like those of 2-PDT on TrkC+ tumors. In contrast, 1-PDT caused dramatic TrkC+ tumor volume reduction (96% from initial) relative to the TrkC- tumors or 2-PDT in TrkC+ models. Moreover, 71% of the mice treated with 10 mg/kg 1-PDT (n = 7) showed full tumor remission and survived until 90 days with no metastasis to key organs. PMID:25487316

  18. Targeted PDT Agent Eradicates TrkC Expressing Tumors via Photodynamic Therapy (PDT)

    PubMed Central

    2015-01-01

    This contribution features a small molecule that binds TrkC (tropomyosin receptor kinase C) receptor that tends to be overexpressed in metastatic breast cancer cells but not in other breast cancer cells. A sensitizer for 1O2 production conjugated to this structure gives 1-PDT for photodynamic therapy. Isomeric 2-PDT does not bind TrkC and was used as a control throughout; similarly, TrkC– cancer cells were used to calibrate enhanced killing of TrkC+ cells. Ex vivo, 1- and 2-PDT where only cytotoxic when illuminated, and 1-PDT, gave higher cell death for TrkC+ breast cancer cells. A 1 h administration-to-illumination delay gave optimal TrkC+/TrkC–-photocytotoxicity, and distribution studies showed the same delay was appropriate in vivo. In Balb/c mice, a maximum tolerated dose of 20 mg/kg was determined for 1-PDT. 1- and 2-PDT (single, 2 or 10 mg/kg doses and one illumination, throughout) had similar effects on implanted TrkC– tumors, and like those of 2-PDT on TrkC+ tumors. In contrast, 1-PDT caused dramatic TrkC+ tumor volume reduction (96% from initial) relative to the TrkC– tumors or 2-PDT in TrkC+ models. Moreover, 71% of the mice treated with 10 mg/kg 1-PDT (n = 7) showed full tumor remission and survived until 90 days with no metastasis to key organs. PMID:25487316

  19. Muon colliders

    SciTech Connect

    Palmer, R.B. |; Sessler, A.; Skrinsky, A.

    1996-01-01

    Muon Colliders have unique technical and physics advantages and disadvantages when compared with both hadron and electron machines. They should thus be regarded as complementary. Parameters are given of 4 TeV and 0.5 TeV high luminosity {micro}{sup +}{micro}{sup {minus}}colliders, and of a 0.5 TeV lower luminosity demonstration machine. We discuss the various systems in such muon colliders, starting from the proton accelerator needed to generate the muons and proceeding through muon cooling, acceleration and storage in a collider ring. Problems of detector background are also discussed.

  20. Effect of verteporfin-PDT on epithelial growth factor receptor (EGFR) signaling pathway in cholangiocarcinoma cell lines

    NASA Astrophysics Data System (ADS)

    Andreola, Fausto; Cerec, Virginie; Pereira, Stephen P.

    2009-06-01

    EGFR, a member of the ERBB family, plays a pivotal role in carcinogenesis. EGFR overexpression is implicated in DNA repair and synergistic interactions between EGFR-targeting drugs and conventional chemo/radiotherapy have been reported in preclinical studies for different cancers but not cholangiocarcinoma (CCA). To date there are no in vitro data available on the cellular response and effect of either photodynamic therapy (PDT) or EGFR-targeting drugs on CCA. Therefore, we aimed to study the: (i) response to Verteporfin PDT and to EGFR-targeting drugs, as single agents; (ii) effect of PDT on ERBBs expression, phosporylation status and activation of its signaling pathways; (iii) response to combination of PDT and EGFR-targeting agents. We showed that two cholangiocarcinoma cell lines (HuCCT1 and TFK1 cells, intra- and extrahepatic, respectively) differentially respond to verteporfin-PDT treatment and are resistant to EGFR-targeting agents. A constitutive activation of EGFR in both cell lines was also observed, which could partly account for the observed resistance to EGFR-targeting drugs. In addition, verteporfin-PDT induced further phosphorylation of both EGFR and other Receptor Tyrosine Kinases. Mitochondria-independent apoptosis was induced by PDT in both CCA cell lines; in particular, PDT modulated the expression of members of the Inhibitor of Apoptosis (IAP) family of proteins. Interestingly, there was a PDT-induced EGFR nuclear translocation in both cell lines; co-treatment with either an EGFR-inhibitor (Cetuximab) or a nuclear import blocking agent (Wheat Germ Agglutinin) had an additive effect on PDT cell killing, thus implying a role of EGFR in repairing the potential PDT-induced DNA damage.

  1. Muon Collider

    SciTech Connect

    Palmer, R.

    2009-10-19

    Parameters are given of muon colliders with center of mass energies of 1.5 and 3 TeV. Pion production is from protons on a mercury target. Capture, decay, and phase rotation yields bunch trains of both muon signs. Six dimensional cooling reduces the emittances until the trains are merged into single bunches, one of each sign. Further cooling in 6 dimensions is then applied, followed by final transverse cooling in 50 T solenoids. After acceleration the muons enter the collider ring. Ongoing R&D is discussed.

  2. Assessing PDT response with diffuse optical spectroscopies

    NASA Astrophysics Data System (ADS)

    Rohrbach, Daniel J.

    Photodynamic therapy (PDT) is used to treat a variety of conditions including cancer. Effective PDT requires three components: a photosensitizer (PS), light of a specific wavelength to activate the PS and oxygen. When all three are present in a lesion it leads to cell death and vascular destruction. Optical techniques such as diffuse reflectance spectroscopy (DRS), diffuse fluorescence spectroscopy (DFS) and diffuse correlation spectroscopy (DCS) can be used to quantify vascular parameters and photosensitizer content before and after PDT, providing valuable information for assessing response. For the quantification of vascular parameters, a probe-specific empirical light transport model was developed. A look-up-table was constructed using tissue simulating phantoms made of Intralipid to control the scattering, India Ink to control the absorption and water. The empirical model allowed the quantification of optical properties as well as the vascular parameters blood volume fraction (BVf) and blood oxygen saturation (SO2) with DRS. Blood flow was measured using DCS. For the quantification of PS content two techniques were used. DRS was used to fit the absorption of the PS and DFS measured the fluorescence of the PS. For quantification of PS content from measured fluorescence, a correction factor was developed using Monte Carlo simulations to account for the optical properties at the excitation and emission wavelengths. The three techniques were used to assess PDT response in pre-clinical and clinical studies. For the preclinical study, mice were treated with HPPH-PDT and blood flow was measured continuously with DCS. Blood flow variables were compared to STAT3 crosslinking (a molecular marker for PDT photoreaction) and CD31 staining (to visualize intact endothelial cells after PDT). For the clinical study, patients in a clinical trial for HPPH-PDT were measured with DRS, DFS and DCS before and after treatment. Multiple parameters were compared to the clinical response

  3. Taking PDT into mainstream clinical practice

    NASA Astrophysics Data System (ADS)

    Bown, Stephen G.

    2009-06-01

    Many individuals in the field are frustrated by the slow progress getting PDT established in mainstream clinical practice. The five key reasons are: 1. Lack of adequate evidence of safety and efficacy and optimization of dosimetry. These are fundamental. The number of randomized controlled studies is still small. For some cancer applications, it is difficult to get patients to agree to be randomised, so different approaches must be taken. Anecdotal results are not acceptable to sceptics and regulators. 2. The regulatory processes. The rules get more complex every day, but there is no choice, they must be met. The full bureaucratic strength of the pharmaceutical industry is needed to address these issues. 3. Conservatism of the medical profession. Established physicians are reluctant to change practice, especially if it means referring patients to different specialists. 4. Lack of education. It is amazing how few physicians have even heard of PDT and many that have, are sceptical. The profile of PDT to both the medical profession and the general public needs to be raised dramatically. Patient demand works wonders! 5. Money. Major investment is required to run clinical trials. Pharmaceutical companies may see PDT as a threat (eg reduced market for chemotherapy agents). Licensed photosensitisers are expensive. Why not reduce the price initially, to get the technique established and stimulate demand? PDT has the potential for enormous cost savings for health service providers. With appropriate motivation and resources these problems can be addressed. Possible routes forward will be suggested.

  4. PDT Dose Dosimeter for Pleural Photodynamic Therapy

    PubMed Central

    Kim, Michele M.; Darafsheh, Arash; Ahmad, Mahmoud; Finlay, Jarod C.; Zhu, Timothy C.

    2016-01-01

    PDT dose is the product of the photosensitizer concentration and the light fluence in the target tissue. For improved dosimetry during plural photodynamic therapy (PDT), a PDT dose dosimeter was developed to measure both the light fluence and the photosensitizer concentration simultaneously in the same treatment location. Light fluence and spectral data were rigorously compared to other methods of measurement (e.g. photodiode, multi-fiber spectroscopy contact probe) to assess the accuracy of the measurements as well as their uncertainty. Photosensitizer concentration was obtained by measuring the fluorescence of the sensitizer excited by the treatment light. Fluence rate based on the intensity of the laser spectrum was compared to the data obtained by direct measurement of fluence rate by a fiber-coupled photodiode. Phantom studies were done to obtain an optical property correction for the fluorescence signal. Measurements were performed in patients treated Photofrin for different locations in the pleural cavity. Multiple sites were measured to investigate the heterogeneity of the cavity and to provide cross-validation via relative dosimetry. This novel method will allow for accurate real-time determination of delivered PDT dose and improved PDT dosimetry. PMID:27053825

  5. PDT dose dosimeter for pleural photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Kim, Michele M.; Darafsheh, Arash; Ahmad, Mahmoud; Finlay, Jarod C.; Zhu, Timothy C.

    2016-03-01

    PDT dose is the product of the photosensitizer concentration and the light fluence in the target tissue. For improved dosimetry during plural photodynamic therapy (PDT), a PDT dose dosimeter was developed to measure both the light fluence and the photosensitizer concentration simultaneously in the same treatment location. Light fluence and spectral data were rigorously compared to other methods of measurement (e.g. photodiode, multi-fiber spectroscopy contact probe) to assess the accuracy of the measurements as well as their uncertainty. Photosensitizer concentration was obtained by measuring the fluorescence of the sensitizer excited by the treatment light. Fluence rate based on the intensity of the laser spectrum was compared to the data obtained by direct measurement of fluence rate by a fiber-coupled photodiode. Phantom studies were done to obtain an optical property correction for the fluorescence signal. Measurements were performed in patients treated Photofrin for different locations in the pleural cavity. Multiple sites were measured to investigate the heterogeneity of the cavity and to provide cross-validation via relative dosimetry. This novel method will allow for accurate real-time determination of delivered PDT dose and improved PDT dosimetry.

  6. Can PDT be potentiated by immunotherapy?

    NASA Astrophysics Data System (ADS)

    Korbelik, Mladen; Krosl, Gorazd; Chaplin, David J.

    1993-03-01

    Two principal aspects of interlinkage of the immune system with photodynamic therapy (PDT) treatment are discussed in detail: (1) participation of tumor associated macrophages (TAM) in tumor localization of photosensitizers, and (2) induction of an inflammatory immune response by phototoxic effects in endothelial cells, TAM and other cells in the tumor, leading to necrosis of the tumor tissue. It is illustrated how Photofrin levels in TAM, and consequently in the tumor as a whole, can be altered (increased or decreased) by specific agents that stimulate or impair physiological processes in TAM. It is suggested that the selectivity of tumor localization of some photosensitizers can be augmented by TAM targeted immunotherapy with agents that enhance the rate of tumor infiltration of these cells and stimulate their phagocytic activity. Preliminary results of ongoing studies suggest that PDT induces a massive infiltration of immune cells into the treated tumor. It is hypothesized that by combining PDT with an appropriate type of immunotherapy the immune reaction can be potentiated and directed against the surviving tumor cells. As as an example, it is shown that much better control of SCCVII tumor is achieved by combining PDT with the treatment by the immunoactivator SPG compared to PDT alone.

  7. PD and PDT for hepatoblastoma? Preclinical considerations

    NASA Astrophysics Data System (ADS)

    Stepp, Herbert; Bergmann, Florian; Johansson, Ann; Heide, Michael; Metzger, Roman; Rolle, Udo; Till, Holger

    2011-07-01

    Objective: Provide preclinical data on the feasibility of 5-aminolevulinic acid (5-ALA) -based photodetection (PD) and Photodynamic Therapy (PDT) of early childhood tumors. Methods: Hepatoblastoma (HuH6), neuroblastoma (MHH-NB11) and N1-fibroblast cell lines were tested for their relative capacities to synthesize Protoporphyrin IX (PpIX) from 5-ALA and for their susceptibility to PDT in vitro. HuH6-cells were also inoculated in the peritoneum of rats. The pharmacokinetics of porphyrin accumulation was measured in 9 rats by laparoscopic spectroscopy. 5-ALA was applied by i.p. injection of 500 mg/kg bw. In another 21 animals, tumors (n=20), liver (n=5) and peritoneum (n=4) were treated by PDT laparoscopically. 48 h after irradiation, animals were again incubated with 5-ALA and then sacrificed and tissues were removed for further investigation. Results: Both tumor cell lines showed higher levels of porphyrin fluorescence than the fibroblasts. Cell viability testing proved the HuH6 cells to be most susceptible to PDT. Pharmacokinetic measurements of PpIX in xenografted tumors showed a peak at 80-200 min after i.p. injection of 5-ALA. Irradiation resulted in pronounced photobleaching at all irradiated sites and necrosis of tumor and liver tissue, whereas peritoneum appeared to remain unaffected. Necrosis induced by PDT could be seen in fluorescence microscopy due to the lack of porphyrin synthesis in necrotic tissue after the re-incubation with 5-ALA.

  8. Muon muon collider: Feasibility study

    SciTech Connect

    1996-06-18

    A feasibility study is presented of a 2 + 2 TeV muon collider with a luminosity of L = 10{sup 35} cm{sup {minus}2} s{sup {minus}1}. The resulting design is not optimized for performance, and certainly not for cost; however, it does suffice--the authors believe--to allow them to make a credible case, that a muon collider is a serious possibility for particle physics and, therefore, worthy of R and D support so that the reality of, and interest in, a muon collider can be better assayed. The goal of this support would be to completely assess the physics potential and to evaluate the cost and development of the necessary technology. The muon collider complex consists of components which first produce copious pions, then capture the pions and the resulting muons from their decay; this is followed by an ionization cooling channel to reduce the longitudinal and transverse emittance of the muon beam. The next stage is to accelerate the muons and, finally, inject them into a collider ring which has a small beta function at the colliding point. This is the first attempt at a point design and it will require further study and optimization. Experimental work will be needed to verify the validity of diverse crucial elements in the design.

  9. Hyperglycemia enhances the effectiveness of PDT

    NASA Astrophysics Data System (ADS)

    Fan, Keichun; Huang, Yingcai; Li, Junheng

    1995-05-01

    The effect of injection of 10 mg/g 50% glucose on photodynamic therapy of mouse transplantable S-180 sarcoma was studied. The concentration of hematoporphyrin monomethylether in plasma, skin, and tumor was measured by recording spectrofluorophotometer. tumor pathological section was made and necrosis area of tumor longitudinal section was measured by image processing after photoradiation of gold vapor laser. The results of this study suggested that the uptake of photosensitizer in tumor significantly increased while the uptake of photosensitizer in skin remained unchanged after glucose administration. Furthermore, glucose administration combined with PDT produced a greater tumor necrosis area than using PDT alone. The mechanisms and clinical significance were also discussed.

  10. Comanche airframe design - The PDT approach

    NASA Astrophysics Data System (ADS)

    Kay, Bruce F.

    1993-04-01

    The paper discusses the product development team (PDT) management approach adopted for the airframe design of the RAH-66 Comanche, a new helicopter for armed reconnaissance. One of the Comanche program's most important goals is cost control, and mechanisms for accomplishing this are firmly imbedded in all PDTs. Continuous evaluation of the supportability attributes is performed by PDT members representing different areas. Typical of the analyses used to influence the design is the predictions of maintenance requirements. These data are used, for example, to determine equipment locations; components requiring the most maintenance are placed in the most accessible positions.

  11. Muon Muon Collider: Feasibility Study

    SciTech Connect

    Gallardo, J.C.; Palmer, R.B.; Tollestrup, A.V.; Sessler, A.M.; Skrinsky, A.N.; Ankenbrandt, C.; Geer, S.; Griffin, J.; Johnstone, C.; Lebrun, P.; McInturff, A.; Mills, Frederick E.; Mokhov, N.; Moretti, A.; Neuffer, D.; Ng, K.Y.; Noble, R.; Novitski, I.; Popovic, M.; Qian, C.; Van Ginneken, A. /Fermilab /Brookhaven /Wisconsin U., Madison /Tel Aviv U. /Indiana U. /UCLA /LBL, Berkeley /SLAC /Argonne /Sobolev IM, Novosibirsk /UC, Davis /Munich, Tech. U. /Virginia U. /KEK, Tsukuba /DESY /Novosibirsk, IYF /Jefferson Lab /Mississippi U. /SUNY, Stony Brook /MIT /Columbia U. /Fairfield U. /UC, Berkeley

    2012-04-05

    A feasibility study is presented of a 2 + 2 TeV muon collider with a luminosity of L = 10{sup 35} cm{sup -2}s{sup -1}. The resulting design is not optimized for performance, and certainly not for cost; however, it does suffice - we believe - to allow us to make a credible case, that a muon collider is a serious possibility for particle physics and, therefore, worthy of R and D support so that the reality of, and interest in, a muon collider can be better assayed. The goal of this support would be to completely assess the physics potential and to evaluate the cost and development of the necessary technology. The muon collider complex consists of components which first produce copious pions, then capture the pions and the resulting muons from their decay; this is followed by an ionization cooling channel to reduce the longitudinal and transverse emittance of the muon beam. The next stage is to accelerate the muons and, finally, inject them into a collider ring wich has a small beta function at the colliding point. This is the first attempt at a point design and it will require further study and optimization. Experimental work will be needed to verify the validity of diverse crucial elements in the design. Muons because of their large mass compared to an electron, do not produce significant synchrotron radiation. As a result there is negligible beamstrahlung and high energy collisions are not limited by this phenomena. In addition, muons can be accelerated in circular devices which will be considerably smaller than two full-energy linacs as required in an e{sup +} - e{sup -} collider. A hadron collider would require a CM energy 5 to 10 times higher than 4 TeV to have an equivalent energy reach. Since the accelerator size is limited by the strength of bending magnets, the hadron collider for the same physics reach would have to be much larger than the muon collider. In addition, muon collisions should be cleaner than hadron collisions. There are many detailed particle

  12. ALA-mediated fluorescence-guided resection (FGR) and PDT of glioma

    NASA Astrophysics Data System (ADS)

    Johansson, Ann; Stepp, Herbert; Beck, Tobias; Beyer, Wolfgang; Pongratz, Thomas; Sroka, Ronald; Meinel, Thomas; Stummer, Walter; Kreth, Friedrich-Wilhelm; Tonn, Jörg-Christian; Baumgartner, Reinhold

    2009-06-01

    A summary of clinical trials employing photodynamic diagnosis (PDD) and photodynamic therapy (PDT) for the diagnosis and treatment of brain malignancies is presented. Intra-cavity PDT has been performed within the surgical cavity following FGR, employing oral administration of 5-aminolevulinic acid (5-ALA), either targeting fluorescing tissue regions that were not removed during FGR due to safety reasons (referred to as focal PDT, n=20) or illuminating the entire resection cavity (referred to as integral PDT, n=9). Both approaches proved technically feasible and safe. Spectroscopic measurements performed pre-, during and post-PDT revealed Protoporphyrin IX (PpIX)-photobleaching of more than 95% after the delivery of 200 J/cm2. This light dose did not induce any side effects. Furthermore, interstitial PDT (iPDT) has been employed within one feasibility trial (n=10) and one Phase I/II trial (n=15). Here, three to six cylindrical light diffusors (20-30 mm length, 200 mW/cm, 720 J/cm) were positioned within the target tissue under stereotactic guidance. Pre-treatment planning was performed with the intent to target the entire tumour volume with a sufficient light dose while also minimising the risk of any light-induced temperature increase. For the feasibility trial patients with small, recurrent gliomas were included, resulting in a median survival of 15 months as well as some unexpected longterm survivals (up to 5 years). The Phase I/II trial employed the same clinical procedures. Here, the 12-month survival was 35% and the median progression-free survival was 6 months. In summary, stereotactic iPDT in combination with treatment-planning could be shown to be a safe and feasible treatment modality. These trials are presently being extended to also include on-line monitoring of PpIX fluorescence and photobleaching kinetics. Preliminary data has revealed dramatically different PpIX levels and photobleaching kinetics. Such data could possibly be employed for realtime

  13. Enhancing protoporphyrin IX-induced PDT

    NASA Astrophysics Data System (ADS)

    Curnow, Alison; Pye, Andrew; Campbell, Sandra

    2009-06-01

    Photodynamic therapy (PDT) using porphyrin precursors is commonly used in dermatology. Evidence indicates that good clinical outcomes (associated with excellent cosmesis) can be achieved in superficial precancers and basal cell carcinoma (BCC), however, efficacy appears less favorable for thicker nodular BCC (nBCC) unless multiple PDT treatment cycles are performed. Enhancement is therefore required if nBCC lesions are to be treated effectively with a single PDT treatment. The most common technique currently being routinely employed clinically is the use of aminolevulinic acid (ALA) esters (usually methyl (MAL) or hexyl (HAL)). Standard dermatological PDT employing these porphyrin precursors already manipulates the normal heme biosynthesis pathway resulting in a temporary accumulation of the natural photosensitizer, protoporphyrin IX (PpIX). Further manipulation using iron chelating agents is possible however. In normal and malignant human cells in vitro, the novel iron chelating agent CP94 produced greater PPIX fluorescence when administered with ALA or MAL than either congener produced alone. CP94 was also significantly more effective than the clinically established iron chelating agent desferrioxamine (DFO). Topical application of ALA+CP94 to clinical nBCC lesions was a simple and safe treatment modification which produced a significant increase in clinical clearance when CP94 was included in the cream.

  14. PDT dose dosimetry for pleural photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Sharikova, Anna V.; Finlay, Jarod C.; Liang, Xing; Zhu, Timothy C.

    2013-03-01

    PDT dose is the product of the photosensitizer concentration and the light fluence in target tissue. Although existing systems are capable of measuring the light fluence in vivo, the concurrent measurement of photosensitizer in the treated tissue so far has been lacking. We have developed and tested a new method to simultaneously acquire light dosimetry and photosensitizer fluorescence data via the same isotropic detector, employing treatment light as the excitation source. A dichroic beamsplitter is used to split light from the isotropic detector into two fibers, one for light dosimetry, the other, after the 665 nm treatment light is removed by a band-stop filter, to a spectrometer for fluorescence detection. The light fluence varies significantly during treatment because of the source movement. The fluorescence signal is normalized by the light fluence measured at treatment wavelength. We have shown that the absolute photosensitizer concentration can be obtained by an optical properties correction factor and linear spectral fitting. Tissue optical properties are determined using an absorption spectroscopy probe immediately before PDT at the same sites. This novel method allows accurate real-time determination of delivered PDT dose using existing isotropic detectors, and may lead to a considerable improvement of PDT treatment quality compared to the currently employed systems. Preliminary data in patient studies is presented.

  15. A treatment planning system for pleural PDT

    NASA Astrophysics Data System (ADS)

    Sandell, Julia; Chang, Chang; Finlay, Jarod C.; Zhu, Timothy C.

    2010-02-01

    Uniform light fluence distribution for patients undergoing photodynamic therapy (PDT) is critical to ensure predictable PDT outcome. However, common practice uses a point source to deliver light to the pleural cavity. To improve the uniformity of light fluence rate distribution, we have developed a treatment planning system using an infrared camera to track the movement of the point source. This study examines the light fluence (rate) delivered to chest phantom to simulate a patient undergoing pleural PDT. Fluence rate (mW/cm2) and cumulative fluence (J/cm2) was monitored at 7 different sites during the entire light treatment delivery. Isotropic detectors were used for in-vivo light dosimetry. Light fluence rate in the pleural cavity is also calculated using the diffusion approximation with a finite-element model. We have established a correlation between the light fluence rate distribution and the light fluence rate measured on the selected points based on a spherical cavity model. Integrating sphere theory is used to aid the calculation of light fluence rate on the surface of the sphere as well as inside tissue assuming uniform optical properties. The resulting treatment planning tool can be valuable as a clinical guideline for future pleural PDT treatment.

  16. Comparison of two phthalocyanines for PDT

    NASA Astrophysics Data System (ADS)

    Bachor, Ruediger; Reich, Ella D.; Graf, Peter; Rueck, Angelika C.; Hautmann, Richard E.

    1996-01-01

    Photodynamic therapy (PDT) is a new treatment modality for bladder carcinoma, especially carcinoma in situ. The goal of our study was to compare two different phthalocyanines for PDT of bladder carcinoma cells and to evaluate phototoxic potential. Material and methods: For PDT hydrophilic chlor-aluminum sulfonated phthalocyanine (CASP) and lipophilic zinc- phthalocyanine (ZnP, CPG 55 847) were compared. For ZnP liposomes as drug carrier were used. The photosensitizer concentrations for both substances used for PDT experiments were 5, 10 and 20 (mu) g/ml. Irradiation was performed with a Penta lamp emitting at wavelengths between 590 and 900 nm at a fluence of up to 12 J/cm2. After irradiation cells were incubated for two days, counted and compared with a control group. Results: The cell survival rate was decreased depending on the light and drug dose. After incubation with the highest drug dose and irradiation with 12 J/cm2 cell survival was 0.03 and 5.5% after incubation with CASP or ZnP, respectively. Light, CASP or ZnP alone had no effect on cells. Studies of the PDT effect by electron microscopy showed intracellular vacuolization caused by mitochondrial damage after incubation with either photosensitizer. Conclusion: The hydrophilic and lipophilic phthalocyanine tested here showed very similar effects on our cell line. ZnP is a pure compound and hence has some advantage over CASP, which is a mixture of a tri- and tetrasulfonated phthalocyanine. In addition, ZnP is administered in liposomes which should enhance tumor selectivity by binding to low density lipoprotein receptors on tumor cells.

  17. Mechanistic exploration of a bi-directional PDT-based combination in pancreatic cancer (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Huang, Huang-Chiao; Mallidi, Srivalleesha; Liu, Joyce; Chiang, Chun-Te; Mai, Zhiming; Goldschmidt, Ruth; Rizvi, Imran; Ebrahim-Zadeh, Neema; Hasan, Tayyaba

    2016-03-01

    It is increasingly evident that the most effective cancer treatments will involve interactive regimens that target multiple non-overlapping pathways, preferably such that each component enhances the others to improve outcomes while minimizing systemic toxicities. Toward this goal, we developed a combination of photodynamic therapy and irinotecan, which mechanistically cooperate with each other, beyond their individual tumor destruction pathways, to cause synergistic reduction in orthotopic pancreatic tumor burden. A three-way mechanistic basis of the observed the synergism will be discussed: (i) PDT downregulates drug efflux transporters to increase intracellular irinotecan levels. (ii) Irinotecan reduces the expression of hypoxia-induced marker, which is upregulated by PDT. (iii) PDT downregulates irinotecan-induced survivin expression to amplify the apoptotic and anti-proliferative effects. The clinical translation potential of the combination will also be highlighted.

  18. Polarized muon beams for muon collider

    NASA Astrophysics Data System (ADS)

    Skrinsky, A. N.

    1996-11-01

    An option for the production of intense and highly polarized muon beams, suitable for a high-luminosity muon collider, is described briefly. It is based on a multi-channel pion-collection system, narrow-band pion-to-muon decay channels, proper muon spin gymnastics, and ionization cooling to combine all of the muon beams into a single bunch of ultimately low emittance.

  19. Mitochondrion-mediated apoptosis induced by photofrin-PDT

    NASA Astrophysics Data System (ADS)

    Wu, Yunxia; Xing, Da

    2007-05-01

    Apoptosis is an important cellular event that plays a key role in pathogeny and therapy of many diseases. The mechanisms of the initiation and regulation of PDT-induced apoptosis are complex. Some PDT-associated apoptosis pathways involved plasma membrane death receptors, mitochondria, lysosomes and endoplasmic reticulum (ER). In order to determine the apoptosis pathway induced by Photofrin-PDT, we used fluorescence resonance energy transfer (FRET) technique and probe SCAT3 to monitor the dynamics of caspase-3 activation after PDT treatment and also measured caspase-8 activity. With laser scanning confocal microscopy, we found that Photofrin were localized primarily in mitochondria, the primary targets of Photofrin-PDT. Formation of mitochondrial reactive oxygen species (ROS) was detected within minutes after PDT treatment. This was followed by mitochondrial membrane potential (ΔΨm), cytochrome c release, caspase-9 activity, caspase-3 activity and apoptosis. After PDT treatment, caspase-3 was activated rapidly while caspase-8 remained inactivated. Our results indicated that PDT-induced apoptosis was initiated from mitochondria pathway and independent of caspase-8 activation. The activation of caspase-3 by PDT started 20 minutes after treatment and completed in about 15 minutes. PDT-induced apoptosis is directly initiated from mitochondria pathway and not involved in the death receptors-dependent pathway. Our results demonstrated that FRET could be an effective tool to determine PDT-induced apoptosis and other cell death mechanism.

  20. Mechanistic studies on a sequential PDT protocol

    NASA Astrophysics Data System (ADS)

    Kessel, David

    2016-03-01

    A low (~LD15) PDT dose resulting in selective lysosomal photodamage can markedly promote photokilling by subsequent photodamage targeted to mitochondria. Experimental data are consistent with the proposal that cleavage of the autophagyassociated protein ATG5 to a pro-apoptotic fragment is responsible for this effect. This process is known to be dependent on the proteolytic activity of calpain. We have proposed that Ca2+ released from photodamaged lysosomes is the trigger for ATG5 cleavage. We can now document the conversion of ATG5 to the truncated form after lysosomal photodamage. Photofrin, a photosensitizer that targets both mitochondria and lysosomes, can be used for either phase of the sequential PDT process. The ability of Photofrin to target both loci may explain the well-documented efficacy of this agent.

  1. Cell death pathways associated with PDT

    NASA Astrophysics Data System (ADS)

    Kessel, David; Reiners, John J., Jr.

    2006-02-01

    Photodynamic therapy leads to both direct and indirect tumor cell death. The latter also involves the consequences of vascular shut-down and immunologic effects. While these factors are a major factor in tumor eradication, there is usually an element of direct cell killing that can reduce the cell population by as much as 2-3 logs. Necrosis was initially believed to represent the predominant PDT death mechanism. An apoptotic response to PDT was first reported by Oleinick in 1991, using a sensitizer that targets the anti-apoptotic protein Bcl-2. Apoptosis leads to fragmentation of DNA and of cells into apoptotic bodies that are removed by phagocytosis. Inflammatory effects are minimized, and the auto- catalytic elements of the process can amplify the death signal. In this study, we examined consequences of Bcl-2 photodamage by a porphycene sensitizer that targets the ER and causes photodamage to the anti-apoptotic protein Bcl-2. Death patterns after Bcl-2 inactivation by a small-molecular antagonist were also assessed. In addition to apoptosis, we also characterized a hitherto undescribed PDT effect, the initiation of autophagy. Autophagy was initially identified as a cell survival pathway, allowing the recycling of components as nutrients become scarce. We propose that autophagy can also represent both a potential survival pathway after PDT damage to cellular organelles, as well as a cell-death pathway. Recent literature reports indicate that autophagy, as well as apoptosis, can be evoked after down-regulation of Bcl-2, a result consistent with results reported here.

  2. Animal models for photodynamic therapy (PDT)

    PubMed Central

    Silva, Zenildo Santos; Bussadori, Sandra Kalil; Fernandes, Kristianne Porta Santos; Huang, Ying-Ying; Hamblin, Michael R.

    2015-01-01

    Photodynamic therapy (PDT) employs non-toxic dyes called photosensitizers (PSs), which absorb visible light to give the excited singlet state, followed by the long-lived triplet state that can undergo photochemistry. In the presence of ambient oxygen, reactive oxygen species (ROS), such as singlet oxygen and hydroxyl radicals are formed that are able to kill cancer cells, inactivate microbial pathogens and destroy unwanted tissue. Although there are already several clinically approved PSs for various disease indications, many studies around the world are using animal models to investigate the further utility of PDT. The present review will cover the main groups of animal models that have been described in the literature. Cancer comprises the single biggest group of models including syngeneic mouse/rat tumours that can either be subcutaneous or orthotopic and allow the study of anti-tumour immune response; human tumours that need to be implanted in immunosuppressed hosts; carcinogen-induced tumours; and mice that have been genetically engineered to develop cancer (often by pathways similar to those in patients). Infections are the second biggest class of animal models and the anatomical sites include wounds, burns, oral cavity, ears, eyes, nose etc. Responsible pathogens can include Gram-positive and Gram-negative bacteria, fungi, viruses and parasites. A smaller and diverse group of miscellaneous animal models have been reported that allow PDT to be tested in ophthalmology, atherosclerosis, atrial fibrillation, dermatology and wound healing. Successful studies using animal models of PDT are blazing the trail for tomorrow's clinical approvals. PMID:26415497

  3. Direct imaging of macrophage activation during PDT treatment

    NASA Astrophysics Data System (ADS)

    Song, Sheng; Zhou, Feifan; Chen, Wei R.; Xing, Da

    2012-03-01

    Mounting evidence describes a more complex progress of macrophage activation during photodynamic therapy (PDT), which performing distinct immunological functions and different physiologies on surrounding cells and tissues. Macrophage-targeted PDT has been applied in the selective killing of cells involved in inflammation and tumor. We have previously shown that PDT-mediated tumor cells apoptosis can induce a higher level immune response than necrosis, and enhance the macrophage activation. However, the molecular mechanism of macrophage activation during PDT-induced apoptotic cells (AC) still unclear. Here, we use confocal microscopy to image the phagocytosis of tumor cells by macrophages. We also observed that PDT-treated AC can activate Toll-like receptors (TLRs) which are present on macrophages surface. Besides, the increase in nitric oxide (NO) formation in macrophages was detected in real time by a laser scanning microscopy. This study provided more details for understanding the molecular mechanism of the immune response induced by PDT-treated AC.

  4. Direct imaging of macrophage activation during PDT treatment

    NASA Astrophysics Data System (ADS)

    Song, Sheng; Zhou, Feifan; Chen, Wei R.; Xing, Da

    2011-11-01

    Mounting evidence describes a more complex progress of macrophage activation during photodynamic therapy (PDT), which performing distinct immunological functions and different physiologies on surrounding cells and tissues. Macrophage-targeted PDT has been applied in the selective killing of cells involved in inflammation and tumor. We have previously shown that PDT-mediated tumor cells apoptosis can induce a higher level immune response than necrosis, and enhance the macrophage activation. However, the molecular mechanism of macrophage activation during PDT-induced apoptotic cells (AC) still unclear. Here, we use confocal microscopy to image the phagocytosis of tumor cells by macrophages. We also observed that PDT-treated AC can activate Toll-like receptors (TLRs) which are present on macrophages surface. Besides, the increase in nitric oxide (NO) formation in macrophages was detected in real time by a laser scanning microscopy. This study provided more details for understanding the molecular mechanism of the immune response induced by PDT-treated AC.

  5. Effects of PDT on the endocytic pathway

    NASA Astrophysics Data System (ADS)

    Kessel, David

    2010-02-01

    Two lines of evidence point to an early effect of photodamage on membrane trafficking. [1] Internalization of a fluorescent probe for hydrophobic membrane loci was impaired by prior photodamage. [2] Interference with the endocytic pathway by the PI-3 kinase antagonist wortmannin led to accumulation of cytoplasmic vacuoles suggesting a block in the recycling of plasma membrane components. Prior photodamage blocked this pathway so that no vacuoles were formed upon exposure of cells to wortmannin. In a murine hepatoma line, the endocytic pathway was preferentially sensitive to lysosomal photodamage. The role of photodamage to the endocytic pathway as a factor in PDT efficacy remains to be assessed.

  6. Development of an applicator for multiphoton PDT

    NASA Astrophysics Data System (ADS)

    Graschew, Georgi; Bastian, Matthias; Rakowsky, Stefan; Roelofs, Theo A.; Balanos, Evangelos; Schlag, Peter M.; Steinmeyer, Gunter; Elsaesser, Thomas

    2004-09-01

    Multiphoton excitation of photosensitizers for laser induced fluorescence diagnosis (LIFD) and photodynamic therapy (PDT) of tumors has the advantage of greater tissue penetration due to the longer wavelength of irradiation. However, multiphoton LIFD and PDT are presently not clinically applicable as there are no applicators available for the delivery of the pulsed laser radiation to the operating room. As an approach, in this contribution the beam delivery through photonic crystal fibers has been investigated. Pulses of a Ti:sapphire laser of 100 fs pulse duration and an average power of 150 mW have been transported through such a fiber of 25 m length and the resulting pulses show the absence of nonlinear contributions but still a broadening of the pulse to 2 ps due to the dispersion of the fiber. It is planned to compensate this broadening by a grating in front of the fiber. Alternatively, the transport of laser radiation of 150 fs and 100 mW through a mirror-joint-arm used for conventional CO2 lasers has been tested showing no broadening of the laser pulses. Two-photon photodynamic activity of mTHPC-CMPEG4 shall serve as a test of the laser light transport system.

  7. An IR Navigation System for Pleural PDT

    NASA Astrophysics Data System (ADS)

    Zhu, Timothy; Liang, Xing; Kim, Michele; Finlay, Jarod; Dimofte, Andreea; Rodriguez, Carmen; Simone, Charles; Friedberg, Joseph; Cengel, Keith

    2015-03-01

    Pleural photodynamic therapy (PDT) has been used as an adjuvant treatment with lung-sparing surgical treatment for malignant pleural mesothelioma (MPM). In the current pleural PDT protocol, a moving fiber-based point source is used to deliver the light. The light fluences at multiple locations are monitored by several isotropic detectors placed in the pleural cavity. To improve the delivery of light fluence uniformity, an infrared (IR) navigation system is used to track the motion of the light source in real-time at a rate of 20 - 60 Hz. A treatment planning system uses the laser source positions obtained from the IR camera to calculate light fluence distribution to monitor the light dose uniformity on the surface of the pleural cavity. A novel reconstruction algorithm is used to determine the pleural cavity surface contour. A dual-correction method is used to match the calculated fluences at detector locations to the detector readings. Preliminary data from a phantom shows superior light uniformity using this method. Light fluence uniformity from patient treatments is also shown with and without the correction method.

  8. PDT of the endometrium using ALA

    NASA Astrophysics Data System (ADS)

    Gannon, Michael J.; Vernon, David I.; Holroyd, J. Andrew; Stringer, Mark R.; Johnson, Nick; Brown, Stanley B.

    1997-05-01

    There is a widely recognized need for new approaches to effect endometrial ablation as an alternative to hysterectomy for treatment of menorrhagia. Photodynamic therapy (PDT) offers one such approach. We have investigated the use of 5-aminolaevulinic acid (ALA)-based PDT of the endometrium in model systems and in a series of patients. In all of this work, the ALA was administrated directly into the uterine cavity to reduce any possibility of systemic photosensitization. In a series of experiments in perfused ex vivo uteri, ALA was introduced into the cavity and protoporphyrin formation was measured in the endometrium, the underlying myometrium and the perfusate. ALA transfer into the perfusate was also measured. This work demonstrated that protoporphyrin formation in the endometrium was approximately ten fold that in the underlying myometrium and that systemic photosensitization would be unlikely to result form transfer of administered ALA from the uterus into the circulation. Similar results were found in studies carried out in vivo, where ALA was administered to patients scheduled for hysterectomy. Using a specially designed light source, the first patients have now been treated by giving intrauterine ALA followed by laser light. Two series of treatments - 10 in all - have been carried out. Eight patients have one year follow up. A reduction in measured menstrual blood loss was demonstrated in all but one patient. Complete symptomatic relief was obtained in tow women who did not require further treatment.

  9. Muons in gamma showers

    NASA Technical Reports Server (NTRS)

    Stanev, T.; Vankov, C. P.; Halzen, F.

    1985-01-01

    Muon production in gamma-induced air showers, accounting for all major processes. For muon energies in the GeV region the photoproduction is by far the most important process, while the contribution of micron + micron pair creation is not negligible for TeV muons. The total rate of muons in gamma showers is, however, very low.

  10. PDT: special cases in front of legal regulations

    NASA Astrophysics Data System (ADS)

    Fischer, E.; Wegner, A.; Pfeiler, T.; Mertz, M.

    2002-10-01

    Introduction: The classic indication for photodynamic therapy (PDT) in ophthalmology is currently represented by classic subfoveal choroidal neovascularisation (CNV) due to age-related macular degeneration (AMD). PDT is a method, which almost selectively causes endothelial damage in neovascular lesions, followed by vascular occlusion and involution of the CNV. The mechanistic aspect suggests that non AMD-related choroidal neovascularisations might also benefit from PDT. PDT in AMD: Within the German health system, PDT indications follow the criteria based on the inclusion criteria of the TAP studies. For instance the CNV should be predominantly classic and located under the center of the foveal avascular zone. In the diagnosis and follow-up of exudative AMD, visual acuity measurements and fluorescein angiography are the established parameters. Retinal thickness analyzer (RTA) measurements might give further information. Before PDT, they show a significant retinal thickening due to intra- and subretinal exudation. Following PDT, early RTA follow-ups show a clear decrease in retinal thickening accompanies by increasing or stable acuity. PDT in CNV of other origins than AMD: New studies support a new spectrum of indications for PDT, hopefully leading to general cost reimbursement for patients. PDT should be viewed as a general method for vascular occlusion and does not represent a causal therapy for progressive exudative AMD. We present patients with CNV due to pathologic myopia, angioid streaks and POHS. Conclusion: The selective vascular occlusion caused by PDT, besides CNV associated with AMD and pathologic myopia, may also allow the treatment of choroidal neovascularisations based on other entities. Careful individual evaluation of those cases is recommended. Despite this wide array of possible indications, cost reimbursement has been limited to classic subfoveal CNV in AMD, although single case reimbursements in choroidal neovascular lesions due to pathologic

  11. Effect of verteporfin-PDT on the Notch signaling pathway in cholangiocarcinoma (CCA) cell lines

    NASA Astrophysics Data System (ADS)

    Cerec, Virginie; Andreola, Fausto; Pereira, Stephen P.

    2009-06-01

    Accumulating preclinical and clinical evidence supports a pro-oncogenic function for Notch signaling in several solid tumors. Therefore, Notch inhibitory agents, such as gamma-secretase inhibitors (GSI), are being investigated as cancer therapeutic agents and a potential adjuvant to conventional chemo/radiotherapy. To date, no in vitro data are available on the cellular response and effect of either photodynamic therapy (PDT) or GSI on human cholangiocarcinoma (CCA). Consequently, we aimed to study the: (i) constitutive expression of Notch signaling pathway in CCA cell lines; (ii) response to Verteporfin-PDT and to GSI, as single agents on CCA cell lines; (iii) effect of Verteporfin-PDT on Notch signaling pathway expression. Expression of Notch signaling components was studied in two cholangiocarcinoma cell lines, HuCCT1 and TFK-1 (intra- and extrahepatic, respectively). No difference in basal expression of Notch1, 2 and Jagged1 was observed in either cell line. In contrast, Notch3 was found to be weakly and highly expressed in HuCCT1 and TFK-1 cells, respectively - supporting our recent microarray data which showed Notch3 overexpression in biliary brushings from patients with extrahepatic CCA. HuCCT1 and TFK-1 differentially responded to Verteporfin-PDT treatment; preliminary data showed no clear effect of GSI on proliferation/apoptosis in either cell line following short exposure (6 and 24h). Following Verteporfin-PDT, Notch1, 2 and Jagged-1 expression was down-regulated in both cell lines, while Notch3 expression was unaffected in HuCCT1 cells and down-regulated in TFK-1 cells. The Notch signaling pathway could represent a potential target for combination therapy in CCA treatment.

  12. Host cell infiltration into PDT-treated tumor

    NASA Astrophysics Data System (ADS)

    Korbelik, Mladen; Krosl, Gorazd; Dougherty, Graeme J.; Chaplin, David J.

    1992-06-01

    C3H mice bearing SCCVII squamous cell carcinoma were treated with photodynamic therapy (PDT) 24 hours after receiving Photofrin (25 mg/kg, i.v.). Single cell suspensions obtained by the enzymatic digestion of tumors excised either 30 minutes or 4 hours after PDT were analyzed for the content of host immune cells and colony forming ability of malignant cells. The results were compared to the data obtained with non-treated tumors. It is shown that there is a marked increase in the content of cells expressing Mac-1 (monocytes/macrophages or granulocytes) in the tumor 30 minutes post PDT, while a high level of other leucocytes are found within the tumors by 4 hours after PDT. As elaborated in Discussion, the infiltration rate of host immune cells, dying of malignant tumor cells, and yet unknown death rate of host cells originally present in PDT treated tumor occurring concomitantly during this time period complicates this analysis. The results of this study suggest a massive infiltration of macrophages and other leucocytes in PDT treated SCCVII tumor, supporting the suggestion that a potent immune reaction is one of the main characteristics of PDT action in solid tumors. It remains to be determined to what extent is the activity of tumor infiltrating immune cells responsible for its eradication by PDT.

  13. Activity of glycated chitosan and other adjuvants to PDT vaccines

    NASA Astrophysics Data System (ADS)

    Korbelik, Mladen; Banáth, Judit; Čiplys, Evaldas; Szulc, Zdzislaw; Bielawska, Alicja; Chen, Wei R.

    2015-03-01

    Glycated chitosan (GC), a water soluble galactose-conjugated natural polysaccharide, has proven to be an effective immunoadjuvant for treatment of tumors based on laser thermal therapy. It was also shown to act as adjuvant for tumor therapy with high-intensity ultrasound and in situ photodynamic therapy (PDT). In the present study, GC was examined as potential adjuvant to PDT-generated cancer vaccine. Two other agents, pure calreticulin protein and acid ceramidase inhibitor LCL521, were also tested as prospective adjuvants for use in conjunction with PDT vaccines. Single treatment with GC, included with PDT vaccine cells suspension, improved the therapeutic efficacy when compared to vaccine alone. This attractive prospect of GC application remains to be carefully optimized and mechanistically elucidated. Both calreticulin and LCL521 proved also effective adjuvants when combined with PDT vaccine tumor treatment.

  14. Preparations for Muon Experiments at Fermilab

    SciTech Connect

    Syphers, M.J.; Popovic, M.; Prebys, E.; Ankenbrandt, C.; /Muons Inc., Batavia

    2009-05-01

    The use of existing Fermilab facilities to provide beams for two muon experiments--the Muon to Electron Conversion Experiment (Mu2e) and the New g-2 Experiment--is under consideration. Plans are being pursued to perform these experiments following the completion of the Tevatron Collider Run II, utilizing the beam lines and storage rings used today for antiproton accumulation without considerable reconfiguration.

  15. Squamous cell carcinoma of dogs and cats: an ideal test system for human head and neck PDT protocols

    NASA Astrophysics Data System (ADS)

    Lucroy, Michael D.

    2006-02-01

    Photodynamic therapy (PDT) is ideally suited for the treatment of head and neck cancer (HNC) in humans. Developing useful PDT protocols for HNC is challenging due to the expense of Phase I and II clinical trials. Moreover, the often-poor predictive value of murine models means that photosensitizers may proceed far into development before problems are noted. Dogs and cats with spontaneous oral squamous cell carcinoma (SCC) share striking similarities with humans affected with oral SCC. These similarities include viral and environmental tobacco smoke as risk factors, location-dependent prognoses, and relative resistance to chemotherapy. The relatively large oral cancers encountered in veterinary patients allow for light and drug dosimetry that are directly applicable to humans. The irregular shape of oral SCC allows a rigorous evaluation of novel photodynamic therapy protocols under field conditions. Because spontaneous tumors in dogs and cats arise in an outbred animal population it is possible to observe an intact host response to PDT. The shorter lifespan of dogs and cats allows rapid accrual of endpoint data. External beam radiation therapy and chemotherapy are commonplace in veterinary medicine, making dogs and cats with spontaneous SCC a useful resource to study the interactions with PDT and other cancer treatment modalities. Our preliminary results demonstrate that PDT is well-tolerated by dogs with oral cancer, and a Phase II clinical trial of zinc-phthalocyanine-based photodynamic therapy is underway in dogs with oral SCC. The usefulness of 5-aminolevulinic acid methyl ester-based PDT is being investigated in cats with oral SCC.

  16. PDT: loss of autophagic cytoprotection after lysosomal photodamage

    NASA Astrophysics Data System (ADS)

    Kessel, David; Price, Michael

    2012-02-01

    Photodynamic therapy is known to evoke both autophagy and apoptosis. Apoptosis is an irreversible death pathway while autophagy can serve a cytoprotective function. In this study, we examined two photosensitizing agents that target lysosomes, although they differ in the reactive oxygen species (ROS) formed during irradiation. With both agents, the 'shoulder' on the PDT dose-response curve was substantially attenuated, consistent with loss of a cytoprotective pathway. In contrast, this 'shoulder' is commonly observed when PDT targets mitochondria or the ER. We propose that lysosomal targets may offer the possibility of promoting PDT efficacy by eliminating a potentially protective pathway.

  17. Muon Bunch Coalescing

    SciTech Connect

    Johnson, Rolland P; Ankenbrandt, Charles; Bhat, Chandra; Popovic, Milorad; Bogacz, Alex; Derbenev, Yaroslav

    2007-06-25

    The idea of coalescing multiple muon bunches at high energy to enhance the luminosity of a muon collider provides many advantages. It circumvents space-charge, beam loading, and wakefield problems of intense low energy bunches while restoring the synergy between muon colliders and neutrino factories based on muon storage rings. A sampling of initial conceptual design work for a coalescing ring is presented here.

  18. The CMS muon detector

    NASA Astrophysics Data System (ADS)

    Giacomelli, P.

    2002-02-01

    The muon detection system of the Compact Muon Solenoid experiment is described. It consists of three different detector technologies: drift tubes in the barrel region, cathode strip chambers in the endcap region and resistive plate chambers in both barrel and endcap regions. The CMS muon detection system ensures excellent muon detection and efficient triggering in the pseudorapidity range 0< η<2.4. The most recent developments and some results from the R&D program will also be discussed.

  19. Light dose verification for pleural PDT

    NASA Astrophysics Data System (ADS)

    Sandell, Julia L.; Liang, Xing; Zhu, Timothy

    2012-02-01

    The ability to deliver uniform light dose in Photodynamic therapy (PDT) is critical to treatment efficacy. Current protocol in pleural photodynamic therapy uses 7 isotropic detectors placed at discrete locations within the pleural cavity to monitor light dose throughout treatment. While effort is made to place the detectors uniformly through the cavity, measurements do not provide an overall uniform measurement of delivered dose. A real-time infrared (IR) tracking camera is development to better deliver and monitor a more uniform light distribution during treatment. It has been shown previously that there is good agreement between fluence calculated using IR tracking data and isotropic detector measurements for direct light phantom experiments. This study presents the results of an extensive phantom study which uses variable, patient-like geometries and optical properties (both absorption and scattering). Position data of the treatment is collected from the IR navigation system while concurrently light distribution measurements are made using the aforementioned isotropic detectors. These measurements are compared to fluence calculations made using data from the IR navigation system to verify our light distribution theory is correct and applicable in patient-like settings. The verification of this treatment planning technique is an important step in bringing real-time fluence monitoring into the clinic for more effective treatment.

  20. Role of PDT and lasers in the tracheobronchial tree

    NASA Astrophysics Data System (ADS)

    Beamis, John F.

    1993-07-01

    Multiple centers in this country and throughout the world have documented the efficacy of Photodynamic Therapy (PDT) in the treatment of cancers of the tracheobronchial tree. While PDT can effectively achieve airway patency by treating bulky obstructing tumors, its most promising role for treating tracheobronchial cancers is in the treatment of superficial early stage tumors which can potentially be treated for cure with this technique. Unfortunately more widespread use of PDT awaits FDA approval which will be slow in coming due to the need for randomized controlled studies. Many improvements are needed in the thoracic application of the Nd:YAG Laser and PDT. However efforts to prevent lung cancer and detect early lung tumors may prove more beneficial than improvement of current systems which are all too often utilized on end stage tumors.

  1. PDT for malignant tumors: a clinical analysis of 152 cases

    NASA Astrophysics Data System (ADS)

    Zhuang, Shi-Zhang; Wang, Yun-Zhen; Li, Xin; Zhang, Changjun; Wang, Jian-Zhao; Zhang, Da-Ren

    1993-03-01

    Hematoporphyrin derivative (HPD) laser photodynamic therapy (PDT) was applied for the patients of 152 cases of malignant tumors, including tumors of the lip, tongue, esophagus, urinary bladder, skin, larynx, vagina, etc. Since early 1981 good results have been obtained.

  2. [Use of nanoparticles (NP) in photodynamic therapy (PDT) against cancer].

    PubMed

    Roblero-Bartolón, Gabriela Victoria; Ramón-Gallegos, Eva

    2015-01-01

    Nanotechnology is a promising interdisciplinary field for developing improved methods of diagnosis and treatment of different diseases, including cancer. Give their optical, magnetic, and structural property, the nanoparticles have been proposed to be use in the development of unconventional treatments for cancer such as photodynamic therapy (PDT). In PDT, a photosensitizing agent is used that accumulates in tumor cells, generating reactive oxygen species that causes the death of malignant cells after irradiation with light at a particular wavelength. However, the use of PDT presents different problems in its application due to the characteristics of hydrophobicity of the photosensitizers, which hinder the efficiency of administration and treatment. It is here where the use of nanoparticles is proposed as a delivery vehicle to optimize treatment application. In this review we describe the use of nanoparticles coupled to PDT in the treatment of cancer and its molecular mechanism of action. PMID:25739488

  3. Muon beamline at ISIS

    NASA Astrophysics Data System (ADS)

    Eaton, G. H.; Clarke-Gayther, M. A.; Scott, C. A.; Cox, S. F. J.; Kilcoyne, S. H.

    1994-07-01

    The original pulsed surface muon facility was established at the Rutherford Appleton Laboratory's ISIS in 1987. The facility was then upgraded in 1993 from a single beam line and spectrometer to a triple beam facility with three spectrometers working independently. The layout of ISIS is shown. A plan of the ISIS experimental hall is shown, indicating the respective locations of the neutron beams, the KARMEN neutrino facility and the muon beam line complex. Other topics shown in the report include the following: (1) Muon production; (2) Transport of muons to the experimental areas; (3) Positron elimination from the ISIS muon beam; (4) Creation of three independent beam lines.

  4. Muon Catalyzed Fusion

    NASA Technical Reports Server (NTRS)

    Armour, Edward A.G.

    2007-01-01

    Muon catalyzed fusion is a process in which a negatively charged muon combines with two nuclei of isotopes of hydrogen, e.g, a proton and a deuteron or a deuteron and a triton, to form a muonic molecular ion in which the binding is so tight that nuclear fusion occurs. The muon is normally released after fusion has taken place and so can catalyze further fusions. As the muon has a mean lifetime of 2.2 microseconds, this is the maximum period over which a muon can participate in this process. This article gives an outline of the history of muon catalyzed fusion from 1947, when it was first realised that such a process might occur, to the present day. It includes a description of the contribution that Drachrnan has made to the theory of muon catalyzed fusion and the influence this has had on the author's research.

  5. From molecular PDT damage to cellular PDT responses: attempts at bridging the gap on the role of Bcl-2

    NASA Astrophysics Data System (ADS)

    Usuda, Jitsuo; Xue, Liang-yan; Chiu, Song-mao; Azizuddin, Kashif; Morris, Rachel L.; Mulvihill, John; Oleinick, Nancy L.

    2003-06-01

    Expression of the anti-apoptotic proteins Bcl-2 and/or Bcl-xL is greatly elevated in many advanced cancers, especially those resistant to standard therapies, such as radiation or chemotherapy. It has been suggested that those two proteins would be attractive targets for the development of new cancer treatments. Photodynamic therapy (PDT) with photosensitizers that localize in or target mitochondria, such as the phthalocyanine Pc 4, specifically attack the anti-apoptotic protein Bcl-2, generating a variety of oxidized, complexed, and cleaved photoproducts. The closely related protein Bcl-xL is also a target of Pc 4-PDT. In a recent study employing transient transfection of an expression vector encoding deletion mutants of Bcl-2, we identified the membrane anchorage regions of the protein that are required to form the photosensitive target. In spite of the demonstrated photodamage to Bcl-2 (and Bcl-xL), how the photodamage translates into changes in the sensitivity of cells to PDT-induced apoptosis or other modes of cell death is not clear, and it also remains unclear how elevated amounts of anti-apoptotic proteins in tumors might make them more or less responsive to PDT. In the present study, we have studied the PDT response of MCF7 human breast cancer cells overexpressing wild-type Bcl-2 or certain deletion mutants either in a transient or stable mode. We show that cells expressing modestly elevated amounts (<10-fold increase) of Bcl-2 and in which the pro-apoptotic protein Bax is not upregulated do not differ from the parental cells with respect to PDT-induced cell killing. In contrast, cells expressing higher amounts (>50-fold increase) of Bcl-2 or certain mutants are made significantly more resistant to the induction of apoptosis and the loss of clonogenicity upon exposure to Pc 4-PDT. In the presence of high levels of Bcl-2, extensive photodamage requires higher PDT doses. We conclude that Pc 4-PDT targets Bcl-2 and Bcl-xL, eliminating one mechanism that

  6. Initial targets and cellular responses to PDT

    NASA Astrophysics Data System (ADS)

    Rodriguez, Myriam E.; Azizuddin, Kashif; Chiu, Song-mao; Delos Santos, Grace; Joseph, Sheeba; Xue, Liang-yan; Oleinick, Nancy L.

    2007-02-01

    Pc 4, a photosensitizer first synthesized at Case Western Reserve University and now in clinical trial at University Hospitals of Cleveland, has been shown to bind preferentially and with high affinity to mitochondrial and endoplasmic reticulum membranes. Upon photoirradiation of Pc 4-loaded cells, membrane components are photodamaged. In most cancer cells, apoptosis is triggered by the initial photodamage; however, in cells deficient in one of the critical intermediates of apoptosis, this process does not occur, although the cells remain as sensitive to the lethal effects of Pc 4-PDT as the apoptosis-competent cells, when cell death is determined by colony formation. Here we report that an alternative death process, autophagy, is induced in all cells tested and becomes the dominant pathway for elimination of lethally damaged cells when apoptosis is compromised. The anti-apoptotic protein Bcl-2, when overexpressed, protects only apoptosis-competent cells against loss of clonogenicity, while the autophagy inhibitor 3-methyladenine provides a markedly greater protection to apoptosis-deficient cells. The results suggest that the primary determinant of cell death is not the final pathway for elimination of the cells but the initial photodamage to critical membrane targets. In attempts to identify those targets, we have studied the role of different membrane phospholipids in the localization of Pc 4. Cardiolipin (CL) is a phospholipid found exclusively in the mitochondrial inner membrane and at the contact sites between the inner and outer membranes. Previous fluorescence resonance energy transfer studies revealed colocalization of Pc 4 and CL, which points to CL as a possible binding site and target for Pc 4. Unilamellar liposomes with different lipid compositions were used as membrane models to test the affinity of Pc 4. As revealed by the binding constants, Pc 4 does not display preferential binding to CL in these systems. Moreover, binding affinities appear to be

  7. Biological consequences of PDT: tying up the loose ends

    NASA Astrophysics Data System (ADS)

    Kessel, David; Andrzejak, Michelle; Price, Michael

    2011-02-01

    While many of the determinants of photodynamic tumor eradication have been identified, the story is not yet complete. Fluorescent probes for reactive oxygen species (ROS) are seldom specific, and the role of different ROS in apoptosis vs. autophagy are not fully delineated. Moreover, the conflicting roles of autophagy as both a death and a survival pathway remain to be explained. Most tissue-culture studies are carried out in 20% oxygen although this is far in excess of the environment of malignant cells in vivo. And while apoptotic and/or autophagic death appears to account for the lethal effects of PDT, an effect on membrane recycling has now been identified. In this report, we summarize some recent experiments designed to examine the specificity of fluorescent ROS probes. We also demonstrate the ability of hydrogen peroxide to accelerate the autophagic response to PDT in an adhering cell line, the 1c1c7 murine hepatoma. In this cell line, autophagy appears to be a pro-survival mechanism since a sub-line (KD) depleted in a critical autophagy protein (atg7) was more responsive to PDT than wild-type (WT) cells. There are clearly multiple determinants of direct tumor cell kill by PDT that depend on the PDT target, the ROS produced and phenotypic variations.

  8. Fluorescence Guided PDT for Optimization of Skin Cancer Treatment

    NASA Astrophysics Data System (ADS)

    Blanco, Kate; Moriyama, Lilian; Inada, Natalia; Kurachi, Cristina; Salvio, Ana; Leite, Everson; Menezes, Priscila; Bagnato, Vanderlei

    2015-04-01

    The photodynamic therapy (PDT) is an alternative technique that can be indicated for superficial basal cell carcinoma (sBCC), Bowen’s disease and actinic keratosis with high efficiency. The objective of this study is to present the importance of fluorescence imaging for PDT guidance and monitoring in real time. Confirming that the lesion is well prepared and the photosensitizer shows a homogenous distribution, the outcome after few PDT sessions will be positive and the recurrence should be lower. Our proposition in this study is use the widefield fluorescence imaging to evaluate the PDT protocol in situ and in real time for each lesion. This evaluation procedure is performed in two steps: first with the monitoring of the production of protoporphyrin IX (PpIX) induced by methyl aminolevulinate (MAL), an derivative of 5-aminolevulinic acid (ALA) and second with the detection of PpIX photobleaching after illumination. The fluorescence images provide information correlated with distinct clinical features and with the treatment outcome. Eight BCC lesions are presented and discussed in this study. Different fluorescence patterns of PpIX production and photobleaching could be correlated with the treatment response. The presented results show the potential of using widefield fluorescence imaging as a guidance tool to customized PDT.

  9. Multiple muons in MACRO

    NASA Technical Reports Server (NTRS)

    Heinz, R.

    1985-01-01

    An analysis of the multiple muon events in the Monopole Astrophysics and Cosmic Ray Observatory detector was conducted to determine the cosmic ray composition. Particular emphasis is placed on the interesting primary cosmic ray energy region above 2000 TeV/nucleus. An extensive study of muon production in cosmic ray showers has been done. Results were used to parameterize the characteristics of muon penetration into the Earth to the location of a detector.

  10. The Muon Detector of Cms

    NASA Astrophysics Data System (ADS)

    Jiang, Chunhua

    2005-04-01

    Muons are an unmistakable signature of most of the LHC physics is designed to explore. The ability to trigger on and reconstruct muons at highest luminorsities is central to the concept of CMS. CMS is characterized by simplicity of design, with one magnet whose solenoideal field facilitates precision racking in the central barrel region and triggering on muons through their bending in the tharnverse and side views. The CMS muon system has three purpose: muon identification, muon trigger and nuon momentum measurement.

  11. Brain PDD and PDT unlocking the mystery of malignant gliomas.

    PubMed

    Eljamel, M Sam

    2004-12-01

    Malignant brain tumours (MBTs) have one of the worst outcomes of human cancers today and their incidence is on the increase. Current treatment failure is usually due to local recurrence of the tumour rather than distant metastasis. In the last three decades we have seen many novel and potentially effective treatment strategies rise rapidly to the rescue. Sadly, however, the majority of these approaches were not good enough to withstand the harsh reality of the sceptical gaze of the scientific eye or the stringent health economics of this millennium. PDD and PDT, however, is one of the few therapies fighting back and still standing today. The results of its randomised controlled trials are eagerly awaited. To date the literature suggests that both PDD and PDT significantly prolong the time to tumour progression, reduce local recurrence, increase radical resection and prolong overall survival of MBTs. PDD and PDT are well tolerated by patients and worthwhile pursuing. PMID:25048434

  12. Potential of systemic photosensitizers for PDT of skin malignancies

    NASA Astrophysics Data System (ADS)

    Philipp, Carsten M.; Müller, Ute; Urban, Peter; Berlien, H.-Peter

    2008-04-01

    Usually systemic photosensitizers (PS) require a long period of incubation (48-96h) after systemic admission. On the other hand clearing from healthy skin needs weeks or months. Severe side effects on skin are possible in case of uncontrolled light exposure. Topical PDT may solve this problem, but deep portions may not be sufficiently sensitized, resulting in a survival of some tumor cell population after PDT and recurrence. The same problem counts for actinic keratosis and Bowen's disease, but with even worse consequences as a resulting infiltrating growing squamous cell carcinoma (SCC) is likely to produce metastatic lesions. Light dosimetry is crucial also. Wavelenght, fluence and total energy may influence outcome of any PDT substantially. 17 patients with Bowen's disease or BCC where treated using a novel systemic PS (Fotolon ®) and 665nm light from a diode laser. Follow up time ranges between 2.5 and 1 years after treatment. 2 patients received a second PDT, in 15 patients one treatment was efficient. We found a remissions in 1, local control in 2 and no evidence of disease in 14 patients. Significant fluorescence was noted in all lesions. With a light protection protocol for only 48 hours no severe side effects where seen. One patient developed mild redness of sunlight exposed skin sites 24h after being discharged from light protection protocol. In comparison with currently available topical PS Fotolon ® offers some important advantages as secure photosenzitation of deep portions, single treatment, high selectivity combined with a high cure rate. In comparison with currently available systemic PS Fotolon ® offers short incubation time, high selectivity and short time of elimination, while efficiency was comparable to HPD (hematoporphyrin-derivate) PDT combined with ALA-5 PDT and without need for additional local PS-application for PDD.

  13. Simple optical theory for light dosimetry during PDT (Invited Paper)

    NASA Astrophysics Data System (ADS)

    Jacques, Steven L.

    1992-06-01

    Photons are one of the three major reactants in the photodynamic reaction that yields toxic photoproduct for cell killing. Dosimetry of light is a major concern when planning a photodynamic therapy (PDT) protocol. This paper presents a very simple approach toward the tissue optics with a practical conclusion about how tissue optics affects planning of day-to-day PDT dosimetry. The paper does not address all the complexities of real tissue dosimetry, such as heterogeneous tissues, variable absorption due to changing tissue blood content, and variable tissue oxygen levels. The paper outlines the optical behavior in a homogeneous tissue, which is a starting point for understanding light dosimetry.

  14. Diffractively produced Z bosons in the muon decay channel in p-pbar collisions at s**(1/2) = 1.96 TeV, and the measurement of the efficiency of the D0 Run II luminosity monitor

    SciTech Connect

    Edwards, Tamsin L

    2006-04-01

    The first analysis of diffractively produced Z bosons in the muon decay channel is presented, using data taken by the D0 detector at the Tevatron at {radical}s = 1.96 TeV. The data sample corresponds to an integrated luminosity of 109 pb{sup -1}. The diffractive sample is defined using the fractional momentum loss {zeta} of the intact proton or antiproton measured using the calorimeter and muon detector systems. In a sample of 10791 (Z/{gamma})* {yields} {mu}{sup +}{mu}{sup -} events, 24 diffractive candidate events are found with {zeta} < 0.02. The first work towards measuring the cross section times branching ratio for diffractive production of (Z/{gamma})* {yields} {mu}{sup +}{mu}{sup -} is presented for the kinematic region {zeta} < 0.02. The first work towards measuring the cross section times branching ratio for diffractive production of (Z/{gamma})* {yields} {mu}{sup +}{mu}{sup -} is presented for the kinematic region {zeta} < 0.02. The systematic uncertainties are not yet sufficiently understood to present the cross section result. In addition, the first measurement of the efficiency of the Run II D0 Luminosity Monitor is presented, which is used in all cross section measurements. The efficiency is: {var_epsilon}{sub LM} = (90.9 {+-} 1.8)%.

  15. Rational design of a receptor-targeted photodynamic molecular beacon for the multilevel control of singlet oxygen production and PDT activity in cancer cells

    NASA Astrophysics Data System (ADS)

    Chen, Juan; Stefflova, Klara; Warren, Mike; Bu, Jiachuan; Wilson, Brian C.; Zheng, Gang

    2007-02-01

    Photodynamic therapy (PDT) involves the combined action of light, oxygen and a photosensitizer (PS). It offers unique control in the PS's action because the key cytotoxic agent, singlet oxygen (1O II), is only produced in situ upon irradiation. The 1O II production can be controlled in three levels. The first level involves the judicious use of fiber optics to selectively deliver light to disease tissues. The second level is to exert control over the PS's localization by selectively delivering PS to cancer cells. The third level is to exert control of the PS's ability to generate 1O II in responding to specific cancer biomarkers. Here, we present two PDT agents based on the latter two levels of 1O II control. The first PDT agent "PPF" contains a PS (Pyro) and a tumor homing molecule (folate) and a peptide linker. PPF was found to be selectively accumulated in cancer cells via folate receptor (FR) pathway. The second PDT agent "PP MMP7B" is a matrix metalloproteinase-7 (MMP7)-triggered photodynamic molecular beacon (PMB) containing a PS (Pyro), a 1O II quencher (BHQ3) and a MMP7-cleavable peptide linker. Thus, the 1O II production of PP MMP7B is highly sequence-specific and its photodynamic cytotoxicity is MMP7-dependent. Since these agents are designed to share functional modules (PS and peptide linker) and common cancer cell model (KB cells overexpress both FR and MMP7), it forms the basis for rational design of receptor-targeted PMB for achieving a multi-level control of 1O II production in cancer cells, which in term, could provide a much higher level of PDT selectivity.

  16. Muon and neutrino fluxes

    NASA Technical Reports Server (NTRS)

    Edwards, P. G.; Protheroe, R. J.

    1985-01-01

    The result of a new calculation of the atmospheric muon and neutrino fluxes and the energy spectrum of muon-neutrinos produced in individual extensive air showers (EAS) initiated by proton and gamma-ray primaries is reported. Also explained is the possibility of detecting atmospheric nu sub mu's due to gamma-rays from these sources.

  17. Telecommunication using muon beams

    DOEpatents

    Arnold, Richard C.

    1976-01-01

    Telecommunication is effected by generating a beam of mu mesons or muons, varying a property of the beam at a modulating rate to generate a modulated beam of muons, and detecting the information in the modulated beam at a remote location.

  18. Critical dosimetry measures and surrogate tools that can facilitate clinical success in PDT (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Pogue, Brian W.; Davis, Scott C.; Kanick, Stephen C.; Maytin, Edward V.; Pereira, Stephen P.; Palanisami, Akilan; Hasan, Tayyaba

    2016-03-01

    Photodynamic therapy can be a highly complex treatment with more than one parameter to control, or in some cases it is easily implemented with little control other than prescribed drug and light values. The role of measured dosimetry as related to clinical adoption has not been as successful as it could have been, and part of this may be from the conflicting goals of advocating for as many measurements as possible for accurate control, versus companies and clinical adopters advocating for as few measurements as possible, to keep it simple. An organized approach to dosimetry selection is required, which shifts from mechanistic measurements in pre-clinical and early phase I trials, towards just those essential dose limiting measurements and a focus on possible surrogate measures in phase II/III trials. This essential and surrogate approach to dosimetry should help successful adoption of clinical PDT if successful. The examples of essential dosimetry points and surrogate dosimetry tools which might be implemented in phase II and higher trials are discussed for solid tissue PDT with verteporfin and skin lesion treatment with aminolevulinc acid.

  19. A photobleaching-based PDT dose metric predicts PDT efficacy over certain BPD concentration ranges in a three-dimensional model of ovarian cancer

    NASA Astrophysics Data System (ADS)

    Anbil, S.; Rizvi, I.; Celli, J. P.; Alagic, N.; Hasan, T.

    2013-03-01

    Photodynamic therapy (PDT) dosimetry is an active area of study that is motivated by the need to reliably predict treatment outcomes. Implicit dosimetric parameters, such as photosensitizer (PS) photobleaching, may indicate PDT efficacy and could establish a framework to provide patient-customized PDT. Here, tumor destruction and benzoporphryin-derivative (BPD) photobleaching are characterized by systematically varying BPD-light combinations to achieve fixed PDT doses (M * J * cm-2) in a three-dimensional (3D) model of micrometastatic ovarian cancer (OvCa). It is observed that the BPD-light parameters used to construct a given PDT dose significantly impact nodule viability and BPD photobleaching. As a result, PDT dose, when measured by the product of BPD concentration and fluence, does not reliably predict overall efficacy. A PDT dose metric that incorporates a term for BPD photobleaching more robustly predicts PDT efficacy at low concentrations of BPD. These results suggest that PDT dose metrics that are informed by implicit approaches to dosimetry could improve the reliability of PDT-based regimens and provide opportunities for patient-specific treatment planning.

  20. Preclinical evaluation of zinc phthalocyanine tetrasulfonate-based PDT

    NASA Astrophysics Data System (ADS)

    Borgatti-Jeffreys, Antonella; Hooser, Stephen B.; Miller, Margaret A.; Thomas, Rose M.; deGortari, Amalia; Lucroy, Michael D.

    2005-04-01

    Photodynamic therapy (PDT) involves the light activation of a drug within a tumor causing selective tumor cell death. Unfortunately, some photosensitizing drugs have been associated with adverse reactions in veterinary patients. Zinc phthalocyanine tetrasulfonate (ZnPcS4) is a promising second-generation photosensitizer for use in veterinary medicine, however, it cannot be applied clinically until safety and efficacy data are available. ZnPcS4 was given to Swiss Webster mice to assess acute toxicity. Doses >100 mg/kg were associated with acute toxicity and mortality, and doses >100 mg/kg resulted in renal tubular nephrosis, suggesting that the minimum toxic dose is approximately 100 mg/kg. Based on these data, a Phase I clinical trial of ZnPcS4-based PDT in tumor-bearing dogs is underway, with ZnPcS4 doses up to 2 mg/kg producing no apparent toxicity. Tumor response has been observed after ZnPcS4-based PDT using doses as low as 0.25 mg/kg, suggesting that conventional phase I clinical trials may not be appropriate for PDT protocols.

  1. PDT: Photometric DeTrending Algorithm Using Machine Learning

    NASA Astrophysics Data System (ADS)

    Kim, Dae-Won

    2016-05-01

    PDT removes systematic trends in light curves. It finds clusters of light curves that are highly correlated using machine learning, constructs one master trend per cluster and detrends an individual light curve using the constructed master trends by minimizing residuals while constraining coefficients to be positive.

  2. Techport Input for Propulsive Descent Technologies (PDT) Project

    NASA Technical Reports Server (NTRS)

    Campbell, Charles H.

    2013-01-01

    The PDT project will investigate the use of retro propulsion during the supersonic phase of atmospheric entry for Mars missions. The project technical approach involves a combination of procurement and evaluation of commercially provided flight data, development of candidate vehicle configurations, and engineering calibration of computational fluid dynamics models to the available flight data.

  3. In vivo light dosimetry for HPPH-mediated pleural PDT

    NASA Astrophysics Data System (ADS)

    Dimofte, Andreea; Zhu, Timothy C.; Finlay, Jarod C.; Cullighan, Melissa; Edmonds, Christine E.; Friedberg, Joseph S.; Cengel, Keith; Hahn, Stephen M.

    2010-02-01

    This study examines the light fluence (rate) delivered to patients undergoing pleural PDT as a function of treatment time, treatment volume and surface area. The accuracy of treatment delivery is analyzed as a function of the calibration accuracies of each isotropic detector and the calibration integrating sphere. The patients studied here are enrolled in a Phase I clinical trial of HPPH-mediated PDT for the treatment of non-small cell lung cancer with pleural effusion. Patients are administered 4mg per kg body weight HPPH 24-48 hours before the surgery. Patients undergoing photodynamic therapy (PDT) are treated with light therapy with a fluence of 15-60 J/cm2 at 661nm. Fluence rate (mW/cm2) and cumulative fluence (J/cm2) is monitored at 7 different sites during the entire light treatment delivery. Isotropic detectors are used for in-vivo light dosimetry. The anisotropy of each isotropic detector was found to be within 15%. The mean fluence rate delivery and treatment time are recorded. A correlation between the treatment time and the treatment volume is established. The result can be used as a clinical guideline for future pleural PDT treatment.

  4. PDT in periodontal disease of HAART resistance patients

    NASA Astrophysics Data System (ADS)

    Giovani, Elcio M.; Noro-Filho, Gilberto A.; Caputo, Bruno V.; Casarin, Renato; Costa, Claudio; Salgado, Daniela; Santos, Camila C.

    2016-03-01

    HIV/Aids patients present a change of microbiota associated with host immunodeficiency. Photodynamic therapy (PDT) showed as a promising and viable alternative in reducing microbiota. Present study evaluate effectiveness of photodynamic therapy in periodontal disease of AIDS patients with highly activity antiretroviral therapy (HAART) failure, measuring the clinical periodontal parameters and periodontal microbiota. Twelve patients with HARRT resistance (R group) divided into two groups (control and PDT) and 12 patients with no HAART resistance (NR group) divided into two groups (control and PDT). The results show the difference in baseline of CD4 cells count, NR group 640.0 +/- 176.2 cells/mm3 R group and 333.3 +/- 205.8 cells / mm3 (p<0.05), and in 8.3% detectable viral load in NR group and 75% detectable (p <0.001) in R group. As clinical periodontal parameters (PD and CAL), PDT was more effective than the control group only in the NR group (p <0.05%), moreover, there was no difference in the evaluation of clinical periodontal parameters between the both R groups (p>0.05%). Microbiological evaluation in R group presents a general reduction in the Aa at 3 and 6 months. Furthermore, demonstrated a reduction of Pg in all groups at 6 months and in R group at 3 months. The impact assessment of photodynamic therapy in patients with different levels of immunosuppression determined that the combination of mechanical periodontal treatment with photodynamic therapy in patients with HAART failure did not cause additional benefits. Therefore, PDT in this study could not been indicated in HAART resistance patients.

  5. Underwater measurements of muon intensity

    NASA Technical Reports Server (NTRS)

    Fedorov, V. M.; Pustovetov, V. P.; Trubkin, Y. A.; Kirilenkov, A. V.

    1985-01-01

    Experimental measurements of cosmic ray muon intensity deep underwater aimed at determining a muon absorption curve are of considerable interest, as they allow to reproduce independently the muon energy spectrum at sea level. The comparison of the muon absorption curve in sea water with that in rock makes it possible to determine muon energy losses caused by nuclear interactions. The data available on muon absorption in water and that in rock are not equivalent. Underground measurements are numerous and have been carried out down to the depth of approx. 15km w.e., whereas underwater muon intensity have been measured twice and only down to approx. 3km deep.

  6. Muon Collider Progress: Accelerators

    SciTech Connect

    Zisman, Michael S.

    2011-09-10

    A muon collider would be a powerful tool for exploring the energy-frontier with leptons, and would complement the studies now under way at the LHC. Such a device would offer several important benefits. Muons, like electrons, are point particles so the full center-of-mass energy is available for particle production. Moreover, on account of their higher mass, muons give rise to very little synchrotron radiation and produce very little beamstrahlung. The first feature permits the use of a circular collider that can make efficient use of the expensive rf system and whose footprint is compatible with an existing laboratory site. The second feature leads to a relatively narrow energy spread at the collision point. Designing an accelerator complex for a muon collider is a challenging task. Firstly, the muons are produced as a tertiary beam, so a high-power proton beam and a target that can withstand it are needed to provide the required luminosity of ~1 × 10{sup 34} cm{sup –2}s{sup –1}. Secondly, the beam is initially produced with a large 6D phase space, which necessitates a scheme for reducing the muon beam emittance (“cooling”). Finally, the muon has a short lifetime so all beam manipulations must be done very rapidly. The Muon Accelerator Program, led by Fermilab and including a number of U.S. national laboratories and universities, has undertaken design and R&D activities aimed toward the eventual construction of a muon collider. Design features of such a facility and the supporting R&D program are described.

  7. The Muon Collider

    SciTech Connect

    Zisman, Michael S.

    2011-01-05

    We describe the scientific motivation for a new type of accelerator, the muon collider. This accelerator would permit an energy-frontier scientific program and yet would fit on the site of an existing laboratory. Such a device is quite challenging, and requires a substantial R&D program. After describing the ingredients of the facility, the ongoing R&D activities of the Muon Accelerator Program are discussed. A possible U.S. scenario that could lead to a muon collider at Fermilab is briefly mentioned.

  8. Muons and neutrinos

    NASA Technical Reports Server (NTRS)

    Stanev, T.

    1986-01-01

    The first generation of large and precise detectors, some initially dedicated to search for nucleon decay has accumulated significant statistics on neutrinos and high-energy muons. A second generation of even better and bigger detectors are already in operation or in advanced construction stage. The present set of experimental data on muon groups and neutrinos is qualitatively better than several years ago and the expectations for the following years are high. Composition studies with underground muon groups, neutrino detection, and expected extraterrestrial neutrino fluxes are discussed.

  9. Neutrino physics at muon colliders

    SciTech Connect

    King, B.J.

    1998-03-01

    An overview is given of the neutrino physics potential of future muon storage rings that use muon collider technology to produce, accelerate and store large currents of muons. After a general characterization of the neutrino beam and its interactions, some crude quantitative estimates are given for the physics performance of a muon ring neutrino experiment (MURINE) consisting of a high rate, high performance neutrino detector at a 250 GeV muon collider storage ring.

  10. Antimicrobial photodynamic therapy with RLP068 kills methicillin-resistant Staphylococcus aureus and improves wound healing in a mouse model of infected skin abrasion PDT with RLP068/Cl in infected mouse skin abrasion.

    PubMed

    Vecchio, Daniela; Dai, Tianhong; Huang, Liyi; Fantetti, Lia; Roncucci, Gabrio; Hamblin, Michael R

    2013-09-01

    Photodynamic therapy (PDT) is an alternative treatment for infections that can kill drug resistant bacteria without damaging host-tissue. In this study we used bioluminescent methicillin-resistant Staphylococcus aureus, in a mouse skin abrasion model, to investigate the effect of PDT on bacterial inactivation and wound healing. RLP068/Cl, a tetracationic Zn(II)phthalocyanine derivative and toluidine blue (TBO) were used. The light-dose response of PDT to kill bacteria in vivo and the possible recurrence in the days post-treatment were monitored by real-time bioluminescence imaging, and wound healing by digital photography. The results showed PDT with RLP068/Cl (but not TBO) was able to kill bacteria, to inhibit bacterial re-growth after the treatment and to significantly accelerate the wound healing process (© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim). PMID:22987338

  11. Susceptibility of representative dental pathogens to inactivation by the PDT with water-soluble photosensitizers

    NASA Astrophysics Data System (ADS)

    Angelov, Ivan; Mantareva, Vanya; Kussovski, Veselin; Worle, Diter; Kisov, Hristo; Belcheva, Marieta; Georgieva, Tzvetelina; Dimitrov, Slavcho

    2010-09-01

    In the recent decade the applications of photodynamic therapy (PDT) rapidly increase in several topics and one of areas where the PDT in the future will be play significant role is dentistry. The different photosensitizing complexes with a good water solubility and with absorption with an intensive maximum in the red region (630-690 nm), which makes them suitable for photodynamic treatments, were investigated. The photochemical properties of complexes for singlet oxygen generation were investigated and were shown relations between uptake levels and light intensity to achieve increase in photodynamic efficacy. Photodynamic efficacy against fungi Candida albicans and bacteria's E. faecalis, MRSA and S. Mutans in planktonic media was evaluated. The high photodynamic efficacy was shown for SiPc at very low concentrations (0.9 μM) and light doses of 50 J cm-2 by intensity of light 60 mW cm-2. The photodynamic response for E. faecalis, MRSA and S. Mutans, after treatments with different photosensitizers show strong dependence on concentrations of photsensitzers and micro organisms. The level of inactivation of the pathogen bacteria's from 1-2 degree of initial concentration up to full inactivation was observed. The studied complexes were compared to the recently studied Methylene blue, Haematoporphyrine and tetra-methylpirydiloxy Zn(II)- phthalocyanines and experimental results show that some of them have a good potential for inactivation of representative pathogenic bacterial strains. Experimental results also indicate that photodynamic therapy appears an effective method for inactivation of oral pathogenic bacterias and fungi.

  12. Susceptibility of representative dental pathogens to inactivation by the PDT with water-soluble photosensitizers

    NASA Astrophysics Data System (ADS)

    Angelov, Ivan; Mantareva, Vanya; Kussovski, Veselin; Worle, Diter; Kisov, Hristo; Belcheva, Marieta; Georgieva, Tzvetelina; Dimitrov, Slavcho

    2011-02-01

    In the recent decade the applications of photodynamic therapy (PDT) rapidly increase in several topics and one of areas where the PDT in the future will be play significant role is dentistry. The different photosensitizing complexes with a good water solubility and with absorption with an intensive maximum in the red region (630-690 nm), which makes them suitable for photodynamic treatments, were investigated. The photochemical properties of complexes for singlet oxygen generation were investigated and were shown relations between uptake levels and light intensity to achieve increase in photodynamic efficacy. Photodynamic efficacy against fungi Candida albicans and bacteria's E. faecalis, MRSA and S. Mutans in planktonic media was evaluated. The high photodynamic efficacy was shown for SiPc at very low concentrations (0.9 μM) and light doses of 50 J cm-2 by intensity of light 60 mW cm-2. The photodynamic response for E. faecalis, MRSA and S. Mutans, after treatments with different photosensitizers show strong dependence on concentrations of photsensitzers and micro organisms. The level of inactivation of the pathogen bacteria's from 1-2 degree of initial concentration up to full inactivation was observed. The studied complexes were compared to the recently studied Methylene blue, Haematoporphyrine and tetra-methylpirydiloxy Zn(II)- phthalocyanines and experimental results show that some of them have a good potential for inactivation of representative pathogenic bacterial strains. Experimental results also indicate that photodynamic therapy appears an effective method for inactivation of oral pathogenic bacterias and fungi.

  13. Muons in chemistry

    NASA Astrophysics Data System (ADS)

    Clayden, N. J.

    2013-12-01

    Positive muons have long been used as extrinsic probes in chemistry, offering unique properties for the investigation of local magnetism, dynamics, transport and radical kinetics. Exciting new developments in muon beam lines offer the opportunity of extending these studies selectively to surfaces permitting, for example, the detection of increased mobility of polymer chains at the surface of a polymer film. So called pump and probe methods, involving external perturbations by laser irradiation to manipulate vibrational and electronic states, can be followed by muon pulses allowing the probing of the properties of these states. Muoniated radical probes are finding greater use in soft matter. Selectivity is achieved in these complex systems through an appropriate target molecule giving the chance to measure partitioning and interfacial transfer in surfactant systems. Improvements in sample environments allow the observation of muons in increasingly extreme combinations of temperature and pressure, such as supercritical water, allowing the characterization of the chemistry in these systems.

  14. Study of atmospheric muons using a cosmic ray telescope

    NASA Astrophysics Data System (ADS)

    Abdollahi, S.; Bahmanabadi, M.; Purmohammad, D.

    2013-02-01

    The charge ratio of cosmic muons holds important information for both the atmospheric neutrino anomaly and hadronic interaction models. In this paper we measured the muon charge ratio (R_{\\mu }=N_{\\mu ^{+}}/N_{\\mu ^{-}}) in the cosmic ray flux in the momenta range 0.76-1.60 GeV/c by using a cosmic ray telescope. The delayed coincidence method is used based on the reduced mean lifetime of negative muons due to nuclear capture in matter. The systematic time-dependent effects of the muon charge ratio are considered by grouping the decay data into different time intervals. We compared the experimental data with the predictions of CORSIKA simulations using a high energy interaction model (QGSJET-II) and two low energy interaction models (UrQMD and GHEISHA) in the energy range 1011-1016 eV for primary particles. In addition, by considering the muon flux in different zenithal and azimuthal angles, the muon angular distribution is obtained as I(θ) = I(0)cos nθ with average n = 1.91 ± 0.07. Dependence of the muon flux on the azimuth angle (the East-West effect) is also observed, due to the influence of the geomagnetic field in particular on low energy muons.

  15. Fast cooling, muon acceleration and the prospect of muon colliders

    NASA Astrophysics Data System (ADS)

    Palmer, Mark

    Facilities based on stored muons offer unique potential for future high-energy physics capabilities. Three key characteristics of the muon make this possible: * The muon is a lepton; * The muon is roughly 200 times as massive as the electron; * The muon decays to an electron and two neutrinos. As the next heavier members of the lepton family with respect to the electron and positron, μ+ and μ-. beams can be collided to provide a precision lepton probe of the electroweak couplings. This makes a muon collider a suitable option for a lepton collider companion to a hadron collider discovery machine...

  16. Multi-muon events at CDF

    SciTech Connect

    Ptochos, F.; /Cyprus U.

    2009-07-01

    We report a study of multi-muon events produced at the Fermilab Tevatron collider and recorded by the CDF II detector. In a data set acquired with a dedicated dimuon trigger and corresponding to an integrated luminosity of 2100 pb{sup -1}, we isolate a significant sample of events in which at least one of the identified muons has large impact parameter and is produced outside the beam pipe of radius 1.5 cm. We are unable to fully account for the number and properties of the events through standard model processes in conjunction with our current understanding of the CDF II detector, trigger and event reconstruction. Several topological and kinematic properties of these events are also presented. In contrast, the production cross section and kinematics of events in which both muon candidates are produced inside the beam pipe are successfully modeled by known QCD processes which include heavy flavor production. The presence of these anomalous multi-muon events offers a plausible resolution to long-standing inconsistencies related to b{bar b} production and decay.

  17. Endobronchial occlusive disease: Nd:YAG or PDT?

    NASA Astrophysics Data System (ADS)

    Regal, Anne-Marie; Takita, Hiroshi

    1991-06-01

    Patients with endobronchial occlusion commonly experience dyspnea, cough, hemoptysis, pneumonitis, and atelectasis. If luminal patency is not re-established, obstructive symptoms may progress to sepsis and death. Although the overall survival of patients with lung cancer may not be altered by relief of airway obstruction, the prognosis for this subset of patients may be improved by eliminating the septic complications of bronchial occlusion. Techniques to treat occluded bronchi include electro-fulguration, cryotherapy, brachytherapy, laser (CO2, Nd-YAG) therapy, and photodynamic therapy (PDT). These represent local forms of treatment and are intended to be palliative. Nd-YAG and PDT are the modalities more frequently utilized in this setting. Comparison of the two treatment forms may furnish insight regarding the appropriate role for each as individual therapies and as part of the armamentarium of cancer therapies.

  18. Mars Mission Scenario: Data Volume and PDT Notes

    NASA Technical Reports Server (NTRS)

    Hemmati, Hamid; Biswas, A.; Piazzolla, S.; Townes, S.

    2012-01-01

    Objectives of this work are: (1) Investigate methods for quantifying the value of interoperability for deep space missions: A network of optical receive stations Each one potentially owned by a different space agency. Reduces overall cost to any individual agency Provides geographically diverse locations to mitigate weather problems (clouds, wind, rain, dust, etc.) (2) Metrics: a. Total data volume returned over mission duration b. Percent data transferred (PDT) or something similar.

  19. Ultrasound-guided interventional PDT of liver cancer

    NASA Astrophysics Data System (ADS)

    Zeng, Chaoying; Yang, Dong; Huang, Ping; Zhang, Huijuan; Huang, Muyin; Chen, Ji; Lu, Guorong

    1996-09-01

    Thirty patients with advanced liver cancer were treated by interstitial photodynamic therapy (PDT). These included 28 hepatocellular carcinoma and two adenocarcinoma, 19 primary tumors and 11 recurred follow other treatments. The diameter of tumors were 7-10cm in 13 cases and 10-16cm in 17 cases. In this study, an argon laser pumped dye laser system was used to give a CW laser beam at 630 nm which was split and coupled into there optical fibers. The patients were injected intravenously with photosensitizer hematoporphyrin derivative at a dose of 5mg/kg body weight 48 hours before PDT. Then the fibers were inserted into tumor by ultrasound- guided percutaneous puncture. The inserted irradiation points were spaced in entire tumor with the light release power 300mW and the irradiation time 12 minutes per point. Total 52 treatments were performed in 30 patients. Among them, 14 cases were treated only one time and 16 cases via 2-3 times. The follow-up was carried out in 25 cases for 12- 24 months. The results show that significant remission was 22 percent in those patients by only one treatment and 62 percent in those via 2 to 3 treatments. The shrink rate of tumor size was over 90 percent in five of six cases after treatment 3. The survival time has been over one year in 12 cases. No obvious change to be found for all patients in liver function test, renal function test and blood routine examination. The level of AFP indicated a descending trend after PDT. This work indicate that PDT is effective and safe for the treatment of large liver cancers including those recurred follow hepatic resection and those failed in hepatic artery infusion embolic chemotherapy.

  20. Light dosimetry and dose verification for pleural PDT

    NASA Astrophysics Data System (ADS)

    Dimofte, Andreea; Sharikova, Anna V.; Meo, Julia L.; Simone, Charles B.; Friedberg, Joseph S.; Zhu, Timothy C.

    2013-03-01

    In-vivo light dosimetry for patients undergoing photodynamic therapy (PDT) is critical for predicting PDT outcome. Patients in this study are enrolled in a Phase I clinical trial of HPPH-mediated PDT for the treatment of non-small cell lung cancer with pleural effusion. They are administered 4mg per kg body weight HPPH 48 hours before the surgery and receive light therapy with a fluence of 15-45 J/cm2 at 661 and 665nm. Fluence rate (mW/cm2) and cumulative fluence (J/cm2) are monitored at 7 sites during the light treatment delivery using isotropic detectors. Light fluence (rate) delivered to patients is examined as a function of treatment time, volume and surface area. In a previous study, a correlation between the treatment time and the treatment volume and surface area was established. However, we did not include the direct light and the effect of the shape of the pleural surface on the scattered light. A real-time infrared (IR) navigation system was used to separate the contribution from the direct light. An improved expression that accurately calculates the total fluence at the cavity wall as a function of light source location, cavity geometry and optical properties is determined based on theoretical and phantom studies. The theoretical study includes an expression for light fluence rate in an elliptical geometry instead of the spheroid geometry used previously. The calculated light fluence is compared to the measured fluence in patients of different cavity geometries and optical properties. The result can be used as a clinical guideline for future pleural PDT treatment.

  1. Fractionated PDT with 5-aminolevulinic acid: effective, cost effective, and patient friendly

    NASA Astrophysics Data System (ADS)

    de Vijlder, Hannah C.; Middelburg, Tom A.; de Bruijn, Henriette S.; Robinson, Dominic J.; Neumann, H. A. Martino; de Haas, Ellen R. M.

    2009-06-01

    PDT with ALA and MAL is established as a relatively effective treatment for non-melanoma skin cancer and premalignancies. PDT is often repeated, because a single treatment gives poor long term results. Preclinical studies showed that ALA-PDT applying a fractionated illumination scheme with a small first light fraction and a second larger light fraction separated by a dark interval of two hours resulted in a significant increase in efficacy. Whereas the efficacy was not enhanced by fractionating MAL-PDT, indicating that ALA-PDT mechanism is not the same as MAL-PDT mechanism. The increase in efficacy using fractionated PDT was confirmed clinically. A randomized comparative clinical study comparing fractionated ALA-PDT versus non-fractionated ALA-PDT in the treatment of superficial basal cell carcinoma showed a significant higher response rate in the lesions treated with fractionated ALA-PDT after a follow-up of one year ( p<0.002, log-rank test). The five year follow-up is studied at moment. So far the complete response in the group treated with fractionated ALA-PDT seems to be only a few percentages lower compared to the one year follow-up. Besides the gain in response rate, fractionated ALA PDT is cost effective. ALA gel is less expensive than the commercially available MAL (Metvix) and moreover fractionated ALA-PDT takes one treatment day, instead of two treatment days using the Metvix treatment protocol (two MAL-PDT treatments separated by one week), both reducing direct and indirect costs and the burden to the patient.

  2. PDT-treated apoptotic cells induce macrophage synthesis NO

    NASA Astrophysics Data System (ADS)

    Song, S.; Xing, D.; Zhou, F. F.; Chen, W. R.

    2009-11-01

    Nitric oxide (NO) is a biologically active molecule which has multi-functional in different species. As a second messenger and neurotransmitter, NO is not only an important regulatory factor between cells' information transmission, but also an important messenger in cell-mediated immunity and cytotoxicity. On the other side, NO is involving in some diseases' pathological process. In pathological conditions, the macrophages are activated to produce a large quantity of nitric oxide synthase (iNOS), which can use L-arginine to produce an excessive amount of NO, thereby killing bacteria, viruses, parasites, fungi, tumor cells, as well as in other series of the immune process. In this paper, photofrin-based photodynamic therapy (PDT) was used to treat EMT6 mammary tumors in vitro to induce apoptotic cells, and then co-incubation both apoptotic cells and macrophages, which could activate macrophage to induce a series of cytotoxic factors, especially NO. This, in turn, utilizes macrophages to activate a cytotoxic response towards neighboring tumor cells. These results provided a new idea for us to further study the immunological mechanism involved in damaging effects of PDT, also revealed the important function of the immune effect of apoptotic cells in PDT.

  3. PDT-induced apoptosis in arterial smooth muscles cells

    NASA Astrophysics Data System (ADS)

    Nyamekye, Isaac; Renick, R.; Gilbert, C.; McEwan, Jean R.; Evan, G.; Bishop, Christopher C. R.; Bown, Stephen G.

    1995-03-01

    PDT kills smooth muscle cells (SMC) in vivo and thus prevents intimal hyperplasia after angioplasty. It causes little inflammation and structural integrity of the artery is not compromised. We have studied the process of the SMC death in vitro. Cultured rat SMC (cell line sv40 ATCC) were sensitized with aluminum disulphonated phthalocyanine (AlS2Pc), and then irradiated with 675 nm laser light (2.5 J/cm2). Controls were studied using only sensitizer or laser for treatment. The cells were incubated and the dying process observed with a time lapse video and microscope system. PDT caused a characteristic pattern of death. Cells lost contact with neighbors, shrank, and showed hyperactivity and membrane ruffling. The cells imploded into active and condensed membrane bound vesicles which were terminally reduced to residual bodies. These are the morphological changes of apoptosis. The control cells which were given AlS2Pc alone or laser alone showed no death. PDT induced cultured arterial SMC death by apoptosis rather than necrosis. An apoptotic mechanism of cell death in vivo would explain the relative lack of inflammation and local tissue destruction in the face of massive death.

  4. The in Vitro Antimicrobial Efficacy of PDT against Periodontopathogenic Bacteria

    PubMed Central

    Haag, Philippe A.; Steiger-Ronay, Valerie; Schmidlin, Patrick R.

    2015-01-01

    Periodontitis, an inflammatory disease, is caused by biofilms with a mixed microbial etiology and involves the progressive destruction of the tooth-supporting tissues. A rising number of studies investigate the clinical potential of photodynamic therapy (PDT) as an adjunct during active therapy. The aim of the present review was to evaluate the available literature for the in vitro antimicrobial efficacy of photodynamic therapy focusing on the periodontopathogenic bacteria Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis and Fusobacterium nucleatum. The focused question was: “Is it possible to decrease (at least 3 log steps or 99.9%) or even eliminate bacterial growth by photodynamic therapy in vitro when compared to untreated control groups or control groups treated by placebo?” In general, PDT resulted in a substantial reduction of surviving bacteria. However, not all studies showed the desired reduction or elimination. The ranges of log10-reduction were 0.38 (58%) to a complete eradication (100%) for P. gingivalis, 0.21 (39%) to 100% for A. actinomycetemcomitans and 0.3 (50%) to 100% for F. nucleatum. In conclusion, further and particularly more comparable studies are needed to evaluate if PDT can be clinically successful as an adjuvant in periodontal therapy. PMID:26580607

  5. Using iron chelating agents to enhance dermatological PDT

    NASA Astrophysics Data System (ADS)

    Curnow, Alison; Dogra, Yuktee; Winyard, Paul; Campbell, Sandra

    2009-06-01

    Topical protoporphyrin IX (PPIX) induced photodynamic therapy (PDT) of basal cell carcinoma (BCC) produces good clinical outcomes with excellent cosmesis as long as the disease remains superficial. Efficacy for nodular BCC however appears inferior to standard treatment unless repeat treatments are performed. Enhancement is therefore required and is possible by employing iron chelating agents to temporarily increase PPIX accumulation above the levels normally obtained using aminolevulinic acid (ALA) or the methyl ester of ALA (MAL) alone. In vitro studies investigated the effect of the novel iron chelator, CP94 on necrotic or apoptotic cell death in cultured human skin fibroblasts and epidermal carcinoma cells incubated with MAL. Furthermore, following a dose escalating safety study conducted with ALA in patients, an additional twelve nodular BCCs were recruited for topical treatment with standard MAL-PDT +/- increasing doses of CP94. Six weeks later following clinical assessment, the whole treatment site was excised for histological analysis. CP94 produced greater cell death in vitro when administered in conjunction with MAL than this porphyrin precursor could produce when administered alone. Clinically, PDT treatment using Metvix + CP94 was a simple and safe modification associated with a trend of reduced tumor thickness with increasing CP94 dose.

  6. Approaches to a broad range of high performance PDT sensitizers

    NASA Astrophysics Data System (ADS)

    d'A. Rocha Gonsalves, António M.; Serra, Arménio C.; Pineiro, Marta; Botelho, M. Filomena

    2009-02-01

    Starting from expertise in the area of chemical synthesis, particularly in tetrapyrrolic macrocycles and an interest in modelling structures for particular objectives, we came to the point of aiming at modelling photochemical sensitizers designed for photodynamic therapy (PDT) purposes. Our endeavours were gratifying when it was proved that our synthetic methodologies allowed for the easy availability of properly halogenated porphyrins with high quantum yield singlet oxygen efficiency. Joining the presence of this heavy atom and other functionalities as substituents in selected positions of macrocyclic structures we were able to generate novel porphyrin structures whose photophysical and photochemical properties, singlet oxygen formation quantum yields, photobleaching and logP were measured. Cellular uptake measurements and cytotoxicity assays on WiDr adenocarcinoma and A375 tumor cell lines were carried out and some of our porphyrins demonstrated very high performance as PDT sensitizers comparatively to known compounds approved for clinical use and in the market. Further developments of our studies allowed for the generation of different and more efficient structures, easily made available by our own synthetic methodologies. Our studies in this area allowed us to reach a stage which we believe to correspond to a significant knowledge and capacity to synthesise a broad range of simple structures, whose selectivity and efficiency as PDT sensitizers can be modulated for different cellular and tissue specificities. Our most recent developments in this area will be presented in this communication.

  7. Balancing particle absorption with structural support of the muon beam stop in muons-to-electrons experimental chamber

    SciTech Connect

    Majewski, Ryan

    2013-01-01

    The Mu2e experiment at Fermi National Accelerator Laboratory is seeking a full conversion from muon to electron. The design for Mu2e is based off MECO, another proposed experiment that sought a full conversion from muon to electron at Brookhaven National Laboratory in the 1990s. Mu2e will provide sensitivity that is four times the sensitivity of the previous experiment, SINDRUM II. Discovering muon to electron conversions could help explain physics beyond the standard model of the particle physics.

  8. Adjuvant photodynamic therapy (PDT) with photosensitizer photosens for superficial bladder cancer: experimental investigations to treat prostate cancer by PDT with photosens

    NASA Astrophysics Data System (ADS)

    Apolikhin, Oleg I.; Chernishov, Igor V.; Sivkov, Andrey V.; Altunin, Denis V.; Kuzmin, Sergey G.; Vorozhtsov, Georgy N.

    2007-07-01

    14 patients with transional-cell bladder cancer in stage T1N0M0G2 after transurethral bladder resection were offered adjuvant treatment with PDT. Adjuvant PDT was performed 1-1.5 months after transurethral bladder resection for superficial bladder cancer. Prior to PDT conventional and fluorescent cystoscopy were performed. In the absence of inflammation and after full epitalisation of postoperative wound a session of therapy was performed. 24 hours prior to PDT-session photosensitizer Photosens was injected intravenously in the dose of 0.8 mg per kg of body weight. Prior to PDT local anesthesia of urethra with lidocain-gel was performed. Cystoscopy was carried out. PDT was performed with diode laser "Biospec" (675 nm). During the session the place of standing diffuser and the volume of a bladder were controlled. After 7 months of observation no tumor recidivists were observed. Registered side effects were not life-threatened. 5 patients had pain or discomfort in suprapubic area, ceasing spontaneously or requiring administration of analgetics. No systemic side-effects or allergic reactions were observed. The method can be used in out-patient practice. Absence of early recidivists shows efficiency of PDT in the treatment of superficial bladder cancer. Further study is necessary to estimate optimal regimen of PDT. The further controlling of condition on the patients in this group is required. At the laboratory animals' experiment, we conducted the explorations devoted to the influence of the photodynamic effect at the prostate's tissues.

  9. Fukushima Daiichi Muon Imaging

    NASA Astrophysics Data System (ADS)

    Miyadera, Haruo

    2015-10-01

    Japanese government announced cold-shutdown condition of the reactors at Fukushima Daiichi by the end of 2011, and mid- and long-term roadmap towards decommissioning has been drawn. However, little is known for the conditions of the cores because access to the reactors has been limited by the high radiation environment. The debris removal from the Unit 1 - 3 is planned to start as early as 2020, but the dismantlement is not easy without any realistic information of the damage to the cores, and the locations and amounts of the fuel debris. Soon after the disaster of Fukushima Daiichi, several teams in the US and Japan proposed to apply muon transmission or scattering imagings to provide information of the Fukushima Daiichi reactors without accessing inside the reactor building. GEANT4 modeling studies of Fukushima Daiichi Unit 1 and 2 showed clear superiority of the muon scattering method over conventional transmission method. The scattering method was demonstrated with a research reactor, Toshiba Nuclear Critical Assembly (NCA), where a fuel assembly was imaged with 3-cm resolution. The muon scattering imaging of Fukushima Daiichi was approved as a national project and is aiming at installing muon trackers to Unit 2. A proposed plan includes installation of muon trackers on the 2nd floor (operation floor) of turbine building, and in front of the reactor building. Two 7mx7m detectors were assembled at Toshiba and tested.

  10. Precision muon physics

    NASA Astrophysics Data System (ADS)

    Gorringe, T. P.; Hertzog, D. W.

    2015-09-01

    The muon is playing a unique role in sub-atomic physics. Studies of muon decay both determine the overall strength and establish the chiral structure of weak interactions, as well as setting extraordinary limits on charged-lepton-flavor-violating processes. Measurements of the muon's anomalous magnetic moment offer singular sensitivity to the completeness of the standard model and the predictions of many speculative theories. Spectroscopy of muonium and muonic atoms gives unmatched determinations of fundamental quantities including the magnetic moment ratio μμ /μp, lepton mass ratio mμ /me, and proton charge radius rp. Also, muon capture experiments are exploring elusive features of weak interactions involving nucleons and nuclei. We will review the experimental landscape of contemporary high-precision and high-sensitivity experiments with muons. One focus is the novel methods and ingenious techniques that achieve such precision and sensitivity in recent, present, and planned experiments. Another focus is the uncommonly broad and topical range of questions in atomic, nuclear and particle physics that such experiments explore.

  11. Muon Reconstruction and Identification in CMS

    SciTech Connect

    Everett, A.

    2010-02-10

    We present the design strategies and status of the CMS muon reconstruction and identification identification software. Muon reconstruction and identification is accomplished through a variety of complementary algorithms. The CMS muon reconstruction software is based on a Kalman filter technique and reconstructs muons in the standalone muon system, using information from all three types of muon detectors, and links the resulting muon tracks with tracks reconstructed in the silicon tracker. In addition, a muon identification algorithm has been developed which tries to identify muons with high efficiency while maintaining a low probability of misidentification. The muon identification algorithm is complementary by design to the muon reconstruction algorithm that starts track reconstruction in the muon detectors. The identification algorithm accepts reconstructed tracks from the inner tracker and attempts to quantify the muon compatibility for each track using associated calorimeter and muon detector hit information. The performance status is based on detailed detector simulations as well as initial studies using cosmic muon data.

  12. Photodynamic therapy (PDT) in advanced inoperable bronchial carcinoma

    NASA Astrophysics Data System (ADS)

    Moghissi, Keyvan; Dixon, Kate; Stringer, Mark R.; Brown, Stanley B.

    1996-12-01

    Objective: To assess the efficacy of PDT to: Palliate symptoms, control disease and extend survival in patients with advanced inoperable cancer. Subject and Method: 55 Males and 23 females aged between 45-81 years (mean 66 years) with inoperable and advanced lung cancer with > 5O. obstructive lesions of the main, lobar or segmental bronchi. Patients had pre-treatment routine clinical radiological, functional and endoscopic assessment with proven histological diagnosis. Protocol of PDT was; Intravenous injection of 2 mg/Kg bodyweight Polyhaematoporphyrin (equivalent to Photofrin) or Photofrin followed 24-72 hours later by illumination of tumour using 630 nm light (Oxford Laser) delivered via an optical fibre with end diffuser. Treatments were carried out under general anaesthesia as a day case procedure. Patients were rebronchoscoped for debridement/retreatment 4-7 days later. Results: There was no treatment related mortality. Two patients developed mild photosensitivity reaction. All patients showed symptomatic improvement with good initial functional and radiological amelioration. Every patient responded to treatment. Seven patients had complete response and negative histology for 3-12 months. After the first treatment average Forced Vital Capacity (FVC) and Forced Expiratory Volume in one second (FEV1) improvement was 0.5 litres and 0.4 litres respectively. Twenty five percent of patients (nr 19) survived more than 2 years, 10'. (nr=8) between 1-2 years and the remaining 51 patients less than a year. Conclusion: PDT should be considered as a therapeutic modality for all stages of lung cancer and is an excellent treatment modality for palliation in advanced bronchial malignancies.

  13. PREFACE: Muon spin rotation, relaxation or resonance

    NASA Astrophysics Data System (ADS)

    Heffner, Robert H.; Nagamine, Kanetada

    2004-10-01

    ), is currently being built to replace the current Japanese muSR capability at KEK. These muSR institutions provide scientists a variety of sample environments, including a range of temperatures, magnetic fields and applied pressure. In addition, very low-energy muon beams (< 1 keV) have been developed for studies of thin films and nano-materials. In 2002 this world-wide community founded the International Society of muSR Spectroscopy (http://musr.org/~isms/) in order to promote the health of this growing field of research. The 20 papers presented in this volume are intended to highlight some of the current muSR research activities of interest to condensed matter physicists. It is not an exhaustive review. In particular, the active and exciting area of muonium chemistry is left to a future volume. The group of papers in section I addresses the physics of strongly correlated electrons in solids, one of the most active fields of condensed matter research today. Strong electron correlations arise from (Coulomb) interactions which render Landau's theory of electron transport for weakly interacting systems invalid. Included in this category are unconventional heavy-fermion superconductors, high-temperature copper-oxide superconductors, non-Fermi liquid (NFL) systems and systems with strong electron-lattice-spin coupling, such as the colossal magnetoresistance manganites. Two key properties often make the muon a unique probe of these materials: (1) the muon's large magnetic moment (~3 mup) renders it extremely sensitive to the tiny magnetic fields (~1 Gauss) found, for example, in many NFL systems and in superconductors possessing time-reversal-violating order parameters, and (2) the muon's spin 1/2 creates a simple muSR lineshape (no quadrupolar coupling), ideal for measuring spin-lattice-relaxation, local susceptibilities and magnetic-field distributions in ordered magnets and superconductors. Section II contains studies which exploit the unique sensitivities of muSR just

  14. The LHCb Muon System

    SciTech Connect

    Baldini, W.

    2005-10-12

    In this paper is described the design, the construction and the performances of several Multi Wire Proportional Chamber prototypes built for the LHCb Muon system. In particular we report results for detection efficiency, time resolution, high rate performances and ageing effect measured at the CERN T11 test beam area and at the high irradiation ENEA Casaccia Calliope Facility.

  15. Molecular mechanisms associated with ALA-PDT of brain tumor cells

    NASA Astrophysics Data System (ADS)

    Alqawi, Omar; Espiritu, Myrna; Singh, Gurmit

    2009-06-01

    Previous studies have shown that low-dose PDT using 5-aminolevulinic acid (ALA)-induced photoporphyrin IX (PpIX) can induce apoptosis in tumor cells without causing necrosis. In this study we investigated the molecular mechanisms associated with apoptosis after ALA-PDT treatment in two brain glioma cell lines: human U87, and rat CNS-1cells. We used high energy light at a short time (acute PDT) and low energy light at a long time of exposure (metronomic PDT) to treat both cell lines. The cells were treated with 0.25 mM ALA at 5 joules for energy. We found that CNS-1 cells were more resistant to ALA-PDT than U87 cells when treated by both acute and metronomic PDT. To screen possible apoptosis mechanisms associated with acute and metronomic PDT, microarray analysis of gene expression was performed on RNA from glioblastoma cells treated with either acute or metronomic ALA-PDT. Within the set of genes that were negatively or positively regulated by both treatments are tumor necrosis factor receptors. The expression of TNF receptors was investigated further by RT-PCR and western blotting. The apoptosis mechanism of the cell death occurred through different pathways including BCL-2 and TNF receptors, and in part caused by cleaving caspase 3. Interestingly, metronomic ALA-PDT inhibited the expression of LTβR and the transcription factor NFκB. This inhibition was ALA concentration dependent at low concentrations.

  16. Experimental studies of combination of PDT and tumor chemotherapy or 60Co irradiation

    NASA Astrophysics Data System (ADS)

    Didziapetriene, Janina; Prasmickiene, Grazina; Sukeliene, Dalija; Rotomskis, Ricardas; Streckyte, Giedre; Atkocius, Vydmantas; Staciokiene, Laima; Smilgevicius, Valerijus

    1995-01-01

    We present experimental results obtained by combining photodynamic therapy (PDT) with tumor chemotherapy or radiotherapy. Dimethoxyhematoporphyrin (DMHp) and photosan (PS) were used as photosensitizers, pharanoxi and vincristine as antitumor drugs. The therapeutic effect of the combination of PDT and antitumor drugs (pharanoxi, vincristine) slightly increases as compared to the treatment of PDT or antitumor drug alone. The additive therapeutic effect is achieved under the combination of PDT and 60Co irradiation. It seems that the sensitizers DMHp and PS regulate lipid peroxidation in blood serum of experimental animals, which becomes more active under the influence of alkylating antitumor drugs. Therefore, they could protect an organism from negative influence of tumor chemotherapy.

  17. Topical PDT in the Treatment of Benign Skin Diseases: Principles and New Applications.

    PubMed

    Kim, Miri; Jung, Haw Young; Park, Hyun Jeong

    2015-01-01

    Photodynamic therapy (PDT) uses a photosensitizer, light energy, and molecular oxygen to cause cell damage. Cells exposed to the photosensitizer are susceptible to destruction upon light absorption because excitation of the photosensitizing agents leads to the production of reactive oxygen species and, subsequently, direct cytotoxicity. Using the intrinsic cellular heme biosynthetic pathway, topical PDT selectively targets abnormal cells, while preserving normal surrounding tissues. This selective cytotoxic effect is the basis for the use of PDT in antitumor treatment. Clinically, PDT is a widely used therapeutic regimen for oncologic skin conditions such as actinic keratosis, squamous cell carcinoma in situ, and basal cell carcinoma. PDT has been shown, under certain circumstances, to stimulate the immune system and produce antibacterial, and/or regenerative effects while protecting cell viability. Thus, it may be useful for treating benign skin conditions. An increasing number of studies support the idea that PDT may be effective for treating acne vulgaris and several other inflammatory/infective skin diseases, including psoriasis, rosacea, viral warts, and aging-related changes. This review provides an overview of the clinical investigations of PDT and discusses each of the essential aspects of the sequence: its mechanism of action, common photosensitizers, light sources, and clinical applications in dermatology. Of the numerous clinical trials of PDT in dermatology, this review focuses on those studies that have reported remarkable therapeutic benefits following topical PDT for benign skin conditions such as acne vulgaris, viral warts, and photorejuvenation without causing severe side effects. PMID:26404243

  18. PDT-induced apoptosis: investigations using two malignant brain tumor models

    NASA Astrophysics Data System (ADS)

    Lilge, Lothar D.; Menzies, Keir; Bisland, Stuart K.; Lin, Annie; Wilson, Brian C.

    2002-06-01

    PDT included necrosis in brain tissue and an intracranial tumor has been quantified for various photosensitizers, and it has been shown to be dependent on the sub-cellular localization of these photosensitizers. In quantifying non- necrotic biological endpoints, such as PDT induced apoptosis, the expression and translation of apoptosis inhibiting or promoting genes is of considerable importance. We studied the susceptibility of two glioblastoma cell lines to under go apoptotic cell death following photodynamic treatment with either Photofrin or delta-aminolevulinic acid (delta) ALA) in vivo. Murine 9L Gliosarcoma cells or human U87 Glioblastoma cells were implanted into the cortex of rats, and following 12 or 14 days of growth respectively, subjected to either Photofrin-mediated PDT or ALA-mediated PDT. 9L gliosarcoma cells express the phosphatase Tensin homologue (PTEN) tumor suppressor gene while in U87 cells PTEN is mutated. Differences in the Photofrin mediated PDT induced apoptosis were noted between the two different cell lines in vivo, suggesting that Photofrin mediated PDT may be dependent on apoptotic pathways. ALA induced PPIX showed higher selectivity towards 9L than Photofrin mediated PDT. These studies suggests that PDT could be used as an effective treatment for intracranial neoplasm. Endogenous photosensitizers such as ALA could be used to promote apoptosis in tumor cells due to PDT treatment and thereby minimize the extent of necrotic infarction in the surrounding normal brain.

  19. Topical PDT in the Treatment of Benign Skin Diseases: Principles and New Applications

    PubMed Central

    Kim, Miri; Jung, Haw Young; Park, Hyun Jeong

    2015-01-01

    Photodynamic therapy (PDT) uses a photosensitizer, light energy, and molecular oxygen to cause cell damage. Cells exposed to the photosensitizer are susceptible to destruction upon light absorption because excitation of the photosensitizing agents leads to the production of reactive oxygen species and, subsequently, direct cytotoxicity. Using the intrinsic cellular heme biosynthetic pathway, topical PDT selectively targets abnormal cells, while preserving normal surrounding tissues. This selective cytotoxic effect is the basis for the use of PDT in antitumor treatment. Clinically, PDT is a widely used therapeutic regimen for oncologic skin conditions such as actinic keratosis, squamous cell carcinoma in situ, and basal cell carcinoma. PDT has been shown, under certain circumstances, to stimulate the immune system and produce antibacterial, and/or regenerative effects while protecting cell viability. Thus, it may be useful for treating benign skin conditions. An increasing number of studies support the idea that PDT may be effective for treating acne vulgaris and several other inflammatory/infective skin diseases, including psoriasis, rosacea, viral warts, and aging-related changes. This review provides an overview of the clinical investigations of PDT and discusses each of the essential aspects of the sequence: its mechanism of action, common photosensitizers, light sources, and clinical applications in dermatology. Of the numerous clinical trials of PDT in dermatology, this review focuses on those studies that have reported remarkable therapeutic benefits following topical PDT for benign skin conditions such as acne vulgaris, viral warts, and photorejuvenation without causing severe side effects. PMID:26404243

  20. Overcoming therapeutic resistance in pancreatic cancer is not a simple mix of PDT and chemotherapy: Evaluation of PDT-chemotherapy combinations in 3D tumor models

    NASA Astrophysics Data System (ADS)

    Celli, Jonathan P.; Petrovic, Ljubica; Massdodi, Iqbal; Rizvi, Imran; Hasan, Tayyaba

    2013-03-01

    The dismal survival statistics for pancreatic cancer are due in large part to the notoriously poor response of these tumors to conventional therapies. Here we examine the ability of photodynamic therapy (PDT), using the photosensitizer verteporfin to enhance of the efficacy of traditional chemotherapy agents and/or eradicate populations that are nonresponsive to these agents. Using an in vitro 3D tumor model of pancreatic cancer combined with an imaging-based methodology for quantifying therapeutic response, we specifically examine PDT combination treatments with gemcitabine and oxaliplatin. We show that our 3D cell culture model recapitulates a more clinically-relevant dose response to gemcitabine, with minimal cytotoxic response even at high doses. The same cultures exhibit modest response to PDT treatments, but are also less responsive to this modality relative to our previous reports of monolayer dose response in the same cells. In combination we found no evidence of any enhancement in efficacy of either PDT or gemcitabine treatment regardless of dose or sequence (PDT before gemcitabine, or gemcitabine before PDT). However, when oxaliplatin chemotherapy was administered immediately after treatment with 2.5J/cm2 verteporfin PDT, there was an observable enhancement in response that appears to exceed the additive combination of either treatment alone and suggesting there may be a synergistic interaction. This observation is consistent with previous reports of enhanced efficacy in combinations of PDT with platinum-based chemotherapy. The contrast in results between the combinations examined here underscores the need for rational design of mechanism-based PDT combinations.

  1. Beta-lactamase targeted enzyme activatable photosensitizers for antimicrobial PDT

    NASA Astrophysics Data System (ADS)

    Zheng, Xiang; Verma, Sarika; Sallum, Ulysses W.; Hasan, Tayyaba

    2009-06-01

    Photodynamic therapy (PDT) as a treatment modality for infectious disease has shown promise. However, most of the antimicrobial photosensitizers (PS) non-preferentially accumulate in both bacteria and host tissues, causing host tissue phototoxicity during treatment. We have developed a new antimicrobial PDT strategy which exploits beta-lactam resistance mechanism, one of the major drug-resistance bacteria evolved, to achieve enhanced target specificity with limited host damage. Our strategy comprises a prodrug construct with a PS and a quencher linked by beta-lactam ring, resulting in a diminished phototoxicity. This construct, beta-lactamase enzyme-activated-photosensitizer (beta-LEAP), can only be activated in the presence of both light and bacteria, and remains inactive elsewhere such as mammalian tissue. Beta-LEAP construct had shown specific cleavage by purified beta-lactamase and by beta-lactamase over-expressing methicillin resistant Staphylococcus aureus (MRSA). Specific photodynamic toxicity was observed towards MRSA, while dark and light toxicity were equivalent to reference strains. The prodrug design, synthesis and photophysical properties will be discussed.

  2. Monte Carlo simulation of light fluence calculation during pleural PDT

    NASA Astrophysics Data System (ADS)

    Meo, Julia L.; Zhu, Timothy

    2013-03-01

    A thorough understanding of light distribution in the desired tissue is necessary for accurate light dosimetry in PDT. Solving the problem of light dose depends, in part, on the geometry of the tissue to be treated. When considering PDT in the thoracic cavity for treatment of malignant, localized tumors such as those observed in malignant pleural mesothelioma (MPM), changes in light dose caused by the cavity geometry should be accounted for in order to improve treatment efficacy. Cavity-like geometries demonstrate what is known as the "integrating sphere effect" where multiple light scattering off the cavity walls induces an overall increase in light dose in the cavity. We present a Monte Carlo simulation of light fluence based on a spherical and an elliptical cavity geometry with various dimensions. The tissue optical properties as well as the non-scattering medium (air and water) varies. We have also introduced small absorption inside the cavity to simulate the effect of blood absorption. We expand the MC simulation to track photons both within the cavity and in the surrounding cavity walls. Simulations are run for a variety of cavity optical properties determined using spectroscopic methods. We concluded from the MC simulation that the light fluence inside the cavity is inversely proportional to the surface area.

  3. Real-time treatment feedback guidance of Pleural PDT

    NASA Astrophysics Data System (ADS)

    Zhu, Timothy C.; Kim, Michele M.; Liang, Xing; Liu, Baochang; Meo, Julia L.; Finlay, Jarod C.; Dimofte, Andreea; Rodriguez, Carmen; Simone, Charles; Cengel, Keith; Friedberg, Joseph

    2013-03-01

    Pleural photodynamic therapy (PDT) has been used as an adjuvant treatment with lung-sparing surgical treatment for mesothelioma with remarkable results. In the current intrapleural PDT protocol, a moving fiber-based point source is used to deliver the light and the light dose are monitored by 7 detectors placed in the pleural cavity. To improve the delivery of light dose uniformity, an infrared (IR) camera system is used to track the motion of the light sources. A treatment planning system uses feedback from the detectors as well as the IR camera to update light fluence distribution in real-time, which is used to guide the light source motion for uniform light dose distribution. We have improved the GUI of the light dose calculation engine to provide real-time light fluence distribution suitable for guiding the surgery to delivery light more uniformly. A dual-correction method is used in the feedback system, so that fluence calculation can match detector readings using both direct and scatter light models. An improved measurement device is developed to automatically acquire laser position for the point source. Comparison of the effects of the guidance is presented in phantom study.

  4. A real-time treatment guidance system for pleural PDT

    NASA Astrophysics Data System (ADS)

    Zhu, Timothy C.; Liang, Xing; Sandell, Julia; Finlay, Jarod C.; Dimofte, Andreea; Rodriguez, Carmen; Cengel, Keith; Friedberg, Joseph; Hahn, Stephen M.; Glatstein, Eli

    2012-02-01

    Intrapleural photodynamic therapy (PDT) has been used as an adjuvant treatment with lung-sparing surgical treatment for mesothelioma. In the current intrapleural PDT protocol, a moving fiber-based point source is used to deliver the light and the light dose are monitored by 7 detectors placed in the pleural cavity. To improve the delivery of light dose uniformity, an infrared (IR) camera system is used to track the motion of the light sources. A treatment planning system uses feedback from the detectors as well as the IR camera to update light fluence distribution in real-time, which is used to guide the light source motion for uniform light dose distribution. We have reported previously the success of using IR camera to passively monitor the light fluence rate distribution. In this study, the real-time feedback has been implemented in the current system prototype, by transferring data from the IR camera to a computer at a rate of 20 Hz, and by calculation/displaying using Matlab. A dual-correction method is used in the feedback system, so that fluence calculation can match detector readings. Preliminary data from a phantom showed superior light uniformity using this method. Light fluence uniformity from patient treatments is also shown using the correction method dose model.

  5. Noncoherent light for PDT of spontaneous animal tumors

    NASA Astrophysics Data System (ADS)

    Lucroy, Michael D.; Ridgway, Tisha D.; Higbee, Russell G.; Reeds, Kimberly

    2004-07-01

    Cultured 9L cells were incubated with graded doses of pheophorbide-a-hexyl ether (HPPH) and exposed to 665 nm red light from either a noncoherent light source or a KTP-pumped dye laser. Cell death was observed after irradiation using either light source, with the noncoherent light being most effective at the highest HPPH concentrations. To determing the practicality of using the noncoherent light source for clinical PDT, dogs and cats with spontaneous tumors were injected intravenously with 0.15 mg/kg HPPH one hour before their tumors were irradiated with 665 nm noncoherent light (50 mW cm-2, 100 J cm-2). Of the 9 tumors treated, 8 complete responses were observed, all of which occurred in animals with squamous cell carcinoma. After 68 weeks of follow up, the median initial disease free interval had not been reached. These data support the use of noncoherent light sources for PDT of spontaneous tumors in animals, representing a cost-effective alternative to medical lasers in both veterinary and human dermatology and oncology.

  6. Possible explanation for the low flux of high energy astrophysical muon neutrinos

    SciTech Connect

    Pakvasa, Sandip

    2013-05-23

    I consider the possibility that some exotic neutrino property is responsible for reducing the muon neutrino flux at high energies from distant sources; specifically, (i) neutrino decay and (ii) neutrinos being pseudo-Dirac particles. This would provide a mechanism for the lack of high energy muon events in the Icecube detector.

  7. On muon energy spectrum in muon groups underground

    NASA Technical Reports Server (NTRS)

    Bakatanov, V. N.; Chudakov, A. E.; Novoseltsev, Y. F.; Novoseltseva, M. V.; Stenkin, Y. V.

    1985-01-01

    A method is described which was used to measure muon energy spectrum characteristics in muon groups underground using mu-e decays recording. The Baksan Telescope's experimental data on mu-e decays intensity in muon groups of various multiplicities are analyzed. The experimental data indicating very flat spectrum does not however represent the total spectrum in muon groups. Obviously the muon energy spectrum depends strongly on a distance from the group axis. The core attraction effect makes a significant distortion, making the spectrum flatter. After taking this into account and making corrections for this effect the integral total spectrum index in groups has a very small depencence on muon multiplicity and agrees well with expected one: beta=beta (sub expected) = 1.75.

  8. Muon capture for the front end of a muon collider

    SciTech Connect

    Neuffer, D.; Yoshikawa, C.; /MUONS Inc., Batavia

    2011-03-01

    We discuss the design of the muon capture front end for a {mu}{sup +}-{mu}{sup -} Collider. In the front end, a proton bunch on a target creates secondary pions that drift into a capture transport channel, decaying into muons. A sequence of rf cavities forms the resulting muon beams into strings of bunches of differing energies, aligns the bunches to (nearly) equal central energies, and initiates ionization cooling. The muons are then cooled and accelerated to high energy into a storage ring for high-energy high luminosity collisions. Our initial design is based on the somewhat similar front end of the International Design Study (IDS) neutrino factory.

  9. Muon collider progress

    SciTech Connect

    Noble, Robert J. FNAL

    1998-08-01

    Recent progress in the study of muon colliders is presented. An international collaboration consisting of over 100 individuals is involved in calculations and experiments to demonstrate the feasibility of this new type of lepton collider. Theoretical efforts are now concentrated on low-energy colliders in the 100 to 500 GeV center-of-mass energy range. Credible machine designs are emerging for much of a hypothetical complex from proton source to the final collider. Ionization cooling has been the most difficult part of the concept, and more powerful simulation tools are now in place to develop workable schemes. A collaboration proposal for a muon cooling experiment has been presented to the Fermilab Physics Advisory Committee, and a proposal for a targetry and pion collection channel experiment at Brookhaven National Laboratory is in preparation. Initial proton bunching and space-charge compensation experiments at existing hadron facilities have occurred to demonstrate proton driver feasibility.

  10. Muon spin rotation studies

    NASA Technical Reports Server (NTRS)

    1984-01-01

    The bulk of the muon spin rotation research work centered around the development of the muon spin rotation facility at the Alternating Gradient Synchrotron (AGS) of Brookhaven National Laboratory (BNL). The collimation system was both designed and fabricated at Virginia State University. This improved collimation system, plus improvements in detectors and electronics enabled the acquisition of spectra free of background out to 15 microseconds. There were two runs at Brookhaven in 1984, one run was devoted primarily to beam development and the other run allowed several successful experiments to be performed. The effect of uniaxial strain on an Fe(Si) crystal at elevated temperature (360K) was measured and the results are incorporated herein. A complete analysis of Fe pulling data taken earlier is included.

  11. The role of impurities in molecular solids and biological materials. First-principles study of: I. Helium in solid hydrogen as an obstacle for efficiency of muon catalyzed fusion, and II. Muon and muonium in proteins and DNA as probes for electron transport

    NASA Astrophysics Data System (ADS)

    Scheicher, Ralph H.

    The Hartree-Fock cluster procedure has been used to investigate the electronic structures and associated properties of helium in solid hydrogen and of muon and muonium in cytochrome c and DNA. Our study has shown that He+ is trapped about equally strongly at both tetrahedral and octahedral interstitial sites in solid hydrogen, with almost no dependence of the binding energy on the orientation of the surrounding H2 molecules. Neutral helium appears unbound in solid hydrogen. The results of our calculations provide an explanation for the stronger trapping of helium in the solid phase of hydrogen as compared to the liquid phase, observed in muon catalyzed fusion experiments. Regarding the phenomenon of helium nucleation, our calculations have shown that two He+ ions trapped at adjacent sites in solid hydrogen can substantially reduce their repulsion due to the influence of the H2 molecules. For muon and muonium trapping in cytochrome c, we have shown that the double-bonded oxygen in the carboxyl group is capable of trapping both muon and muonium. This suggests for the muon spin relaxation measurements which study the electron transfer path in cytochrome c, that the muon trapped at this type of oxygen atom is the main one that can sense the movement of the electron that leaves the trapped muonium. Our results provide valuable understanding of the differences between the properties associated with muon and muonium trapped in different amino acids in the protein chain of cytochrome c and the role of environmental effects. Our study of muon and muonium trapping in DNA has shown that significant differences exist in the magnetic hyperfine interaction of muonium trapped in the nucleic acid Adenine between the A-form and B-form DNA type, and the isolated molecule type. This result has potential importance for the interpretation of muon spin relaxation experiments which investigate the dependence of electron mobility upon base pair separation in DNA. The results of our study

  12. ALA-PDT inhibits proliferation and promotes apoptosis of SCC cells through STAT3 signal pathway.

    PubMed

    Qiao, Li; Mei, Zhusong; Yang, Zhiyong; Li, Xinji; Cai, Hong; Liu, Wei

    2016-06-01

    Previous studies suggest that apoptosis of carcinoma cells led by photodynamics is mainly intrinsic apoptosis, but whether the extrinsic pathway is involved in the treatment of carcinoma by photodynamic therapy is not confirmed. This research investigated the effect of ALA-PDT on the proliferation and apoptosis of SCC cell A431 and COLO-16, and discussed the role played by JAK/STAT3 signal pathway in this process. Our data showed that the expression levels STAT3 and p-STAT3 protein in the cancer tissue are higher than the corresponding adjacent tissue to carcinoma. The expression level of p-STAT3 in cancerous tissue has a correlation with the tumor size and tissue histopathological differentiation. ALA-PDT could inhibit proliferation of A431 and COLO-16 cells, STAT3 knock down could enhance ALA-PDT's inhibition of cell proliferation, and promote apoptosis induced by ALA-PDT. On the other hand, overexpression of STAT3 has the opposite effect. In addition, ALA-PDT can weaken the protein expression of STAT3 and its target gene Bcl-2 mRNA, and ALA-PDT can strengthen the protein expression of STAT3's target gene Bax mRNA. Overexpression of STAT3 can offset the effect on Bcl-2 and Bax by ALA-PDT; on the other hand, STAT3 knocking down can strengthen ALA-PDT's effect on Bcl-2 and Bax. PMID:26805005

  13. The US Muon Accelerator Program

    SciTech Connect

    Torun, Y.; Kirk, H.; Bross, A.; Geer, Steve; Shiltsev, Vladimir; Zisman, M.; /LBL, Berkeley

    2010-05-01

    An accelerator complex that can produce ultra-intense beams of muons presents many opportunities to explore new physics. A facility of this type is unique in that, in a relatively straightforward way, it can present a physics program that can be staged and thus move forward incrementally, addressing exciting new physics at each step. At the request of the US Department of Energy's Office of High Energy Physics, the Neutrino Factory and Muon Collider Collaboration (NFMCC) and the Fermilab Muon Collider Task Force (MCTF) have recently submitted a proposal to create a Muon Accelerator Program that will have, as a primary goal, to deliver a Design Feasibility Study for an energy-frontier Muon Collider by the end of a 7 year R&D program. This paper presents a description of a Muon Collider facility and gives an overview of the proposal.

  14. Muon cherenkov telescope

    NASA Astrophysics Data System (ADS)

    Malamova, E.; Angelov, I.; Kalapov, I.; Davidkov, K.; Stamenov, J.

    2001-08-01

    : The Muon Cerenkov Telescope is a system of water cerenkov detectors, using the coincidence technique to register cosmic ray muons. It is constructed in order to study the variations of cosmic rays and their correlation with solar activity and processes in the Earth magnetosphere. 1 Basic design of the Muon Cerenkov Telescope The telescope has 18 water cerenkov detectors / 0.25 m2 each /, situated in two parallel planes. / Fig. 1/ Each detector /fig. 2/ consists of a container with dimensions 50x50x12.5 cm made of 3mm thick glass with mirror cover of the outer side. The container is filled with distilled water to 10cm level. A photomultiplier is attached to a transparent circle at the floor of the container and the discriminator is placed in its housing. When a charged particle with energy greater than the threshold energy for cerenkov radiation generation passes the radiator, cerenkov photons are initiated and a part of them reach the PMT cathode after multiple reflections from the mirror sides of the container.

  15. Muon Colliders and Neutrino Factories

    SciTech Connect

    Geer, Steve; /Fermilab

    2009-11-01

    Over the past decade, there has been significant progress in developing the concepts and technologies needed to produce, capture, and accelerate {Omicron}(10{sup 21}) muons per year. These developments have paved the way for a new type of neutrino source (neutrino factory) and a new type of very high energy lepton-antilepton collider (muon collider). This article reviews the motivation, design, and research and development for future neutrino factories and muon colliders.

  16. Muon colliders and neutrino factories

    SciTech Connect

    Geer, S.; /Fermilab

    2010-09-01

    Over the last decade there has been significant progress in developing the concepts and technologies needed to produce, capture and accelerate {Omicron}(10{sup 21}) muons/year. This development prepares the way for a new type of neutrino source (Neutrino Factory) and a new type of very high energy lepton-antilepton collider (Muon Collider). This article reviews the motivation, design and R&D for Neutrino Factories and Muon Colliders.

  17. Muon Colliders and Neutrino Factories *

    NASA Astrophysics Data System (ADS)

    Geer, Steve

    2009-11-01

    Over the past decade, there has been significant progress in developing the concepts and technologies needed to produce, capture, and accelerate O(1021) muons per year. These developments have paved the way for a new type of neutrino source (neutrino factory) and a new type of very high energy lepton-antilepton collider (muon collider). This article reviews the motivation, design, and research and development for future neutrino factories and muon colliders.

  18. Sensitive detection of PDT-induced cell damages with luminescent oxygen nanosensors

    NASA Astrophysics Data System (ADS)

    Ma, Hong-Ru; Peng, Hong-shang; You, Fang-tian; Ping, Jian-tao; Zhou, Chao; Guo, Lan-ying

    2016-09-01

    In this work luminescent nanosensors specifically created for intracellular oxygen (ic-O2) were utilized to assess photodynamic therapy (PDT) -induced cell damages. Firstly, ic-O2 was demonstrated to be consumed much faster than extracellular O2 with respective O2 nanosensors. Using the ic-O2 nanosensors, PDT-treated cells with different degree of impairment were then resolved according to the oxygen consumption rate (OCR). The evolving trend of cytotoxicity derived from OCRs was in agreement with cell viability obtained from 3-(4,5-cimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Moreover, the direct damage of PDT on cell mitochondria was successfully detected by monitoring respiration instantly after PDT treatment, which is actually beyond the scope of MTT assay. These results suggest that fluorescence sensing of ic-O2-associated cell respiration is promising and even may become a standardized method, complementary to MTT assay, to evaluate PDT-induced cytotoxicity.

  19. Glutamate-mediated protection of crayfish glial cells from PDT-induced apoptosis

    NASA Astrophysics Data System (ADS)

    Rudkovskii, M. V.; Romanenko, N. P.; Berezhnaya, E. V.; Kovaleva, V. D.; Uzdensky, A. B.

    2011-03-01

    Photodynamic treatment that causes intense oxidative stress and kills cells is currently used in neurooncology. However, along with tumor it damages surrounding healthy neurons and glial cells. In order to study the possible role of glutamate-related signaling pathways in photodynamic injury of neurons and glia, we investigated photodynamic effect of alumophthalocyanine Photosens on isolated crayfish stretch receptor that consists of a single neuron surrounded by glial cells. The laser diode (670 nm, 0.4 W/cm2) was used for dye photoexcitation. Application of glutamate increased photodynamically induced necrosis of neurons and glial cells but significantly decreased glial apoptosis. The natural neuroglial mediator N-acetylaspartylglutamate, which releases glutamate after cleavage in the extracellular space by glutamate carboxypeptidase II, also inhibited photoinduced apoptosis. Inhibition of glutamate carboxypeptidase II, oppositely, enhanced apoptosis of glial cells. These data confirm the anti-apoptotic activity of glutamate. Application of NMDA or inhibition of NMDA receptors by MK801 did not influence photodynamic death of neurons and glial cells that indicated nonparticipation of NMDA receptors in these processes. Inhibition of metabotropic glutamate receptors by AP-3 decreased PDT-induced apoptosis. One can suggest that crayfish neurons naturally secrete NAAG, which being cleaved by GCOP produces glutamate. Glutamate prevents photoinduced apoptosis of glial cells possibly through metabotropic but not ionotropic glutamate receptors.

  20. Glutamate-mediated protection of crayfish glial cells from PDT-induced apoptosis

    NASA Astrophysics Data System (ADS)

    Rudkovskii, M. V.; Romanenko, N. P.; Berezhnaya, E. V.; Kovaleva, V. D.; Uzdensky, A. B.

    2010-10-01

    Photodynamic treatment that causes intense oxidative stress and kills cells is currently used in neurooncology. However, along with tumor it damages surrounding healthy neurons and glial cells. In order to study the possible role of glutamate-related signaling pathways in photodynamic injury of neurons and glia, we investigated photodynamic effect of alumophthalocyanine Photosens on isolated crayfish stretch receptor that consists of a single neuron surrounded by glial cells. The laser diode (670 nm, 0.4 W/cm2) was used for dye photoexcitation. Application of glutamate increased photodynamically induced necrosis of neurons and glial cells but significantly decreased glial apoptosis. The natural neuroglial mediator N-acetylaspartylglutamate, which releases glutamate after cleavage in the extracellular space by glutamate carboxypeptidase II, also inhibited photoinduced apoptosis. Inhibition of glutamate carboxypeptidase II, oppositely, enhanced apoptosis of glial cells. These data confirm the anti-apoptotic activity of glutamate. Application of NMDA or inhibition of NMDA receptors by MK801 did not influence photodynamic death of neurons and glial cells that indicated nonparticipation of NMDA receptors in these processes. Inhibition of metabotropic glutamate receptors by AP-3 decreased PDT-induced apoptosis. One can suggest that crayfish neurons naturally secrete NAAG, which being cleaved by GCOP produces glutamate. Glutamate prevents photoinduced apoptosis of glial cells possibly through metabotropic but not ionotropic glutamate receptors.

  1. Light dosimetry technique for endoscopic PDT using microlens optical fiber

    NASA Astrophysics Data System (ADS)

    Jacques, Steven L.

    1999-06-01

    A simple procedure is presented for determining the irradiance of light striking tissues during light delivery using a microlens optical fiber via an endoscope. The particular example is photodynamic therapy (PDT) of laryngeal cancer. A microlens optical fiber is an optical fiber with a small lens assembly at its terminus which magnifies the image of the end of the fiber yielding a uniform irradiance in a plane distant from the fiber. Prior to the therapy, the relation between fiber-target distance, h [cm], and the diameter of the uniform beam, d(h) [cm], was established and the area of the beam was calculated: A(h) equals (pi) d(h)2/4. The laser power P [W] required to achieve a desired irradiance E [W/cm2] was P(h) equals EA(h), and this relation was prepared as a simple graph for routine use in the clinic. During the therapy, the doctor advances the optical fiber through the working channel of the endoscope to touch the target tissue site while observing through the optical channel, and marks the fiber on the outside of the endoscope. The doctor then retracts the fiber until an aiming beam transmitted through the fiber fully illuminates the desired target area, and again marks the fiber on the outside of the endoscope. The difference in the two marks on the fiber outside the endoscope yields h, the height of the fiber above the target tissue. The laser operator then uses the P(h) equals EA(h) graph to select the proper laser power to achieve the desired E. Although trivially simple, this dosimetry procedure was critical to the proper implementation of PDT for laryngeal cancer.

  2. From Neutrino Factory to Muon Collider

    SciTech Connect

    Geer, S.; /Fermilab

    2010-01-01

    Both Muon Colliders and Neutrino Factories require a muon source capable of producing and capturing {Omicron}(10{sup 21}) muons/year. This paper reviews the similarities and differences between Neutrino Factory and Muon Collider accelerator complexes, the ongoing R&D needed for a Muon Collider that goes beyond Neutrino Factory R&D, and some thoughts about how a Neutrino Factory on the CERN site might eventually be upgraded to a Muon Collider.

  3. Physical applications of muon catalysis: Muon capture in hydrogen

    NASA Astrophysics Data System (ADS)

    Filchenkov, V. V.

    2016-07-01

    Results of theoretical and experimental research on capture of negative muons in hydrogen are reported with an emphasis on the accompanying phenomenon of muon catalysis in hydrogen and subtleties of the experimental method. A conclusion is drawn that precise determination of the capture rate is important for refining the standard model.

  4. Muon Spin Rotation Spectroscopy - Utilizing Muons in Solid State Physics

    SciTech Connect

    Suter, Andreas

    2012-10-17

    Over the past decades muon spin rotation techniques (mSR) have established themselves as an invaluable tool to study a variety of static and dynamic phenomena in bulk solid state physics and chemistry. Common to all these approaches is that the muon is utilized as a spin microprobe and/or hydrogen-like probe, implanted in the material under investigation. Recent developments extend the range of application to near surface phenomena, thin film and super-lattice studies. After briefly summarizing the production of so called surface muons used for bulk studies, and discussing the principle differences between pulsed and continuous muon beams, the production of keV-energy muon sources will be discussed. A few topical examples from different active research fields will be presented to demonstrate the power of these techniques.

  5. Electron-Muon Ranger: Performance in the MICE muon beam

    DOE PAGESBeta

    Adams, D.

    2015-12-16

    The Muon Ionization Cooling Experiment (MICE) will perform a detailed study of ionization cooling to evaluate the feasibility of the technique. To carry out this program, MICE requires an efficient particle-identification (PID) system to identify muons. The Electron-Muon Ranger (EMR) is a fully-active tracking-calorimeter that forms part of the PID system and tags muons that traverse the cooling channel without decaying. The detector is capable of identifying electrons with an efficiency of 98.6%, providing a purity for the MICE beam that exceeds 99.8%. Lastly, the EMR also proved to be a powerful tool for the reconstruction of muon momenta inmore » the range 100–280 MeV/c.« less

  6. Electron-Muon Ranger: Performance in the MICE muon beam

    SciTech Connect

    Adams, D.

    2015-12-16

    The Muon Ionization Cooling Experiment (MICE) will perform a detailed study of ionization cooling to evaluate the feasibility of the technique. To carry out this program, MICE requires an efficient particle-identification (PID) system to identify muons. The Electron-Muon Ranger (EMR) is a fully-active tracking-calorimeter that forms part of the PID system and tags muons that traverse the cooling channel without decaying. The detector is capable of identifying electrons with an efficiency of 98.6%, providing a purity for the MICE beam that exceeds 99.8%. Lastly, the EMR also proved to be a powerful tool for the reconstruction of muon momenta in the range 100–280 MeV/c.

  7. An intense low energy muon source for the muon collider

    SciTech Connect

    Taqqu, D.

    1996-05-01

    A scheme for obtaining an intense source of low energy muons is described. It is based on the production of pions in a high field magnetic bottle trap. By ensuring efficient slowing down and extraction of the decay muons an intense intermediate energy muon beam is obtained. For the specific case of negative muons a novel technique called frictional accumulation provides efficient conversion into a 10 keV{mu}{sup {minus}} beam whose emittance is then reduced in a configuration providing extended frictional cooling. The result is a beam of very small transverse and longitudinal emittance that can be used together with an equivalent {mu}{sup +} beam as compact intense muon source for the {mu}{sup +}{mu}{sup {minus}} collider. A final luminosity around 10{sup 34} cm{sup {minus}2}s{sup {minus}1} is expected to be obtained at 2 TeV. {copyright} {ital 1996 American Institute of Physics.}

  8. Electron-muon ranger: performance in the MICE muon beam

    NASA Astrophysics Data System (ADS)

    Adams, D.; Alekou, A.; Apollonio, M.; Asfandiyarov, R.; Barber, G.; Barclay, P.; de Bari, A.; Bayes, R.; Bayliss, V.; Bene, P.; Bertoni, R.; Blackmore, V. J.; Blondel, A.; Blot, S.; Bogomilov, M.; Bonesini, M.; Booth, C. N.; Bowring, D.; Boyd, S.; Bradshaw, T. W.; Bravar, U.; Bross, A. D.; Cadoux, F.; Capponi, M.; Carlisle, T.; Cecchet, G.; Charnley, C.; Chignoli, F.; Cline, D.; Cobb, J. H.; Colling, G.; Collomb, N.; Coney, L.; Cooke, P.; Courthold, M.; Cremaldi, L. M.; Debieux, S.; DeMello, A.; Dick, A.; Dobbs, A.; Dornan, P.; Drielsma, F.; Filthaut, F.; Fitzpatrick, T.; Franchini, P.; Francis, V.; Fry, L.; Gallagher, A.; Gamet, R.; Gardener, R.; Gourlay, S.; Grant, A.; Graulich, J. S.; Greis, J.; Griffiths, S.; Hanlet, P.; Hansen, O. M.; Hanson, G. G.; Hart, T. L.; Hartnett, T.; Hayler, T.; Heidt, C.; Hills, M.; Hodgson, P.; Hunt, C.; Husi, C.; Iaciofano, A.; Ishimoto, S.; Kafka, G.; Kaplan, D. M.; Karadzhov, Y.; Kim, Y. K.; Kuno, Y.; Kyberd, P.; Lagrange, J.-B.; Langlands, J.; Lau, W.; Leonova, M.; Li, D.; Lintern, A.; Littlefield, M.; Long, K.; Luo, T.; Macwaters, C.; Martlew, B.; Martyniak, J.; Masciocchi, F.; Mazza, R.; Middleton, S.; Moretti, A.; Moss, A.; Muir, A.; Mullacrane, I.; Nebrensky, J. J.; Neuffer, D.; Nichols, A.; Nicholson, R.; Nicola, L.; Noah Messomo, E.; Nugent, J. C.; Oates, A.; Onel, Y.; Orestano, D.; Overton, E.; Owens, P.; Palladino, V.; Pasternak, J.; Pastore, F.; Pidcott, C.; Popovic, M.; Preece, R.; Prestemon, S.; Rajaram, D.; Ramberger, S.; Rayner, M. A.; Ricciardi, S.; Roberts, T. J.; Robinson, M.; Rogers, C.; Ronald, K.; Rothenfusser, K.; Rubinov, P.; Rucinski, P.; Sakamato, H.; Sanders, D. A.; Sandström, R.; Santos, E.; Savidge, T.; Smith, P. J.; Snopok, P.; Soler, F. J. P.; Speirs, D.; Stanley, T.; Stokes, G.; Summers, D. J.; Tarrant, J.; Taylor, I.; Tortora, L.; Torun, Y.; Tsenov, R.; Tunnell, C. D.; Uchida, M. A.; Vankova-Kirilova, G.; Virostek, S.; Vretenar, M.; Warburton, P.; Watson, S.; White, C.; Whyte, C. G.; Wilson, A.; Wisting, H.; Yang, X.; Young, A.; Zisman, M.

    2015-12-01

    The Muon Ionization Cooling Experiment (MICE) will perform a detailed study of ionization cooling to evaluate the feasibility of the technique. To carry out this program, MICE requires an efficient particle-identification (PID) system to identify muons. The Electron-Muon Ranger (EMR) is a fully-active tracking-calorimeter that forms part of the PID system and tags muons that traverse the cooling channel without decaying. The detector is capable of identifying electrons with an efficiency of 98.6%, providing a purity for the MICE beam that exceeds 99.8%. The EMR also proved to be a powerful tool for the reconstruction of muon momenta in the range 100-280 MeV/c.

  9. Muon Cooling—emittance exchange

    NASA Astrophysics Data System (ADS)

    Parsa, Zohreh

    2001-05-01

    Muon Cooling is the key factor in building of a Muon collider, (to a less degree) Muon storage ring, and a Neutrino Factory. Muon colliders potential to provide a probe for fundamental particle physics is very interesting, but may take a considerable time to realize, as much more work and study is needed. Utilizing high intensity Muon sources-Neutrino Factories, and other intermediate steps are very important and will greatly expand our abilities and confidence in the credibility of high energy muon colliders. To obtain the needed collider luminosity, the phase-space volume must be greatly reduced within the muon life time. The Ionization cooling is the preferred method used to compress the phase space and reduce the emittance to obtain high luminosity muon beams. We note that, the ionization losses results not only in damping, but also heating. The use of alternating solenoid lattices has been proposed, where the emittance are large. We present an overview of the cooling and discuss formalism, solenoid magnets and some beam dynamics.

  10. High luminosity muon collider design

    SciTech Connect

    Palmer, R.; Gallardo, J.

    1996-10-01

    Muon Colliders have unique technical and physics advantages and disadvantages when compared with both hadron and electron machines. They should be regarded as complementary. Parameters are given of 4 TeV high luminosity {mu}{sup +}{mu}{sup {minus}} collider, and of a 0.5 TeV lower luminosity demonstration machine. We discuss the various systems in such muon colliders.

  11. Pathway-PDT: a flexible pathway analysis tool for nuclear families

    PubMed Central

    2013-01-01

    Background Pathway analysis based on Genome-Wide Association Studies (GWAS) data has become popular as a secondary analysis strategy. Although many pathway analysis tools have been developed for case–control studies, there is no tool that can use all information from raw genotypes in general nuclear families. We developed Pathway-PDT, which uses the framework of Pedigree Disequilibrium Test (PDT) for general family data, to perform pathway analysis based on raw genotypes in family-based GWAS. Results Simulation results showed that Pathway-PDT is more powerful than the p-value based method, ALIGATOR. Pathway-PDT also can be more powerful than the PLINK set-based test when analyzing general nuclear families with multiple siblings or missing parents. Additionally, Pathway-PDT has a flexible and convenient user interface, which allows users to modify their analysis parameters as well as to apply various types of gene and pathway definitions. Conclusions The Pathway-PDT method is implemented in C++ with POSIX threads and is computationally feasible for pathway analysis with large scale family GWAS datasets. The Windows binary along with Makefile and source codes for the Linux are available at https://sourceforge.net/projects/pathway-pdt/. PMID:24006871

  12. Muon collider design

    SciTech Connect

    Palmer, R. |; Sessler, A.; Skrinsky, A.

    1996-03-01

    The possibility of muon colliders was introduced by Skrinsky et al., Neuffer, and others. More recently, several workshops and collaboration meetings have greatly increased the level of discussion. In this paper we present scenarios for 4 TeV and 0.5 TeV colliders based on an optimally designed proton source, and for a lower luminosity 0.5 TeV demonstration based on an upgraded version of the AGS. It is assumed that a demonstration version based on upgrades of the FERMILAB machines would also be possible. 53 refs., 25 figs., 8 tabs.

  13. PREFACE: Muon spin rotation, relaxation or resonance

    NASA Astrophysics Data System (ADS)

    Heffner, Robert H.; Nagamine, Kanetada

    2004-10-01

    ), is currently being built to replace the current Japanese muSR capability at KEK. These muSR institutions provide scientists a variety of sample environments, including a range of temperatures, magnetic fields and applied pressure. In addition, very low-energy muon beams (< 1 keV) have been developed for studies of thin films and nano-materials. In 2002 this world-wide community founded the International Society of muSR Spectroscopy (http://musr.org/~isms/) in order to promote the health of this growing field of research. The 20 papers presented in this volume are intended to highlight some of the current muSR research activities of interest to condensed matter physicists. It is not an exhaustive review. In particular, the active and exciting area of muonium chemistry is left to a future volume. The group of papers in section I addresses the physics of strongly correlated electrons in solids, one of the most active fields of condensed matter research today. Strong electron correlations arise from (Coulomb) interactions which render Landau's theory of electron transport for weakly interacting systems invalid. Included in this category are unconventional heavy-fermion superconductors, high-temperature copper-oxide superconductors, non-Fermi liquid (NFL) systems and systems with strong electron-lattice-spin coupling, such as the colossal magnetoresistance manganites. Two key properties often make the muon a unique probe of these materials: (1) the muon's large magnetic moment (~3 mup) renders it extremely sensitive to the tiny magnetic fields (~1 Gauss) found, for example, in many NFL systems and in superconductors possessing time-reversal-violating order parameters, and (2) the muon's spin 1/2 creates a simple muSR lineshape (no quadrupolar coupling), ideal for measuring spin-lattice-relaxation, local susceptibilities and magnetic-field distributions in ordered magnets and superconductors. Section II contains studies which exploit the unique sensitivities of muSR just

  14. Noninvasive monitoring hemodynamic responses in RIF tumors during and after PDT

    NASA Astrophysics Data System (ADS)

    Yu, Guoqiang; Durduran, Turgut; Busch, Theresa M.; Wang, Hsing-Wen; Zhou, Chao; Saunders, H. Mark; Sehgal, Chandra M.; Yodh, Arjun G.

    2003-06-01

    Changes in blood flow and oxygenation during and after PDT provide information about tumor vessel and cellular damage. The characterization of these changes may improve our understanding of PDT mechanisms and help predict treatment efficacy. We have designed a hybrid system that can non-invasively measure in vivo hemodynamic changes and provide independent information about tumor oxygenation and blood flow. Diffuse correlation spectroscopy (DCS) monitors blood flow by measuring the optical phase shifts caused by moving blood cells, while diffuse photon density wave (DPDW) spectroscopy measures tissue absorption and scattering. When mounted on a camera, our unique probe allows non-contact measurements that avoid compressing the tumor and altering blood flow. An optical filter mounted in front of the camera lens cut off light below 650nm, which allowed monitoring of blood flow during PDT. The utility of the hybrid system was demonstrated by monitoring the hemodynamic changes during and after PDT in mice bearing the experimental radiation-induced fibrosarcoma (RIF). For the first time, we non-invasively and continually monitored the in vivo flow changes during PDT. Relative oxygen consumption was calculated using flow values measured by DCS and oxygenation measured by a broadband absorption spectrometer. During PDT an initial rapid increase in blood flow was found, followed by a decrease and slow recovery. After PDT, substantial and continued reductions in blood saturation, blood flow and oxygen consumption were found after 3 hours, suggesting that permanent damage to tumor cells and blood vessels had occurred. The comparison of flow values after PDT as measured by DCS and by Power Doppler ultrasound (CWFA) demonstrated that both techniques non-invasively detected similar global changes in tumor blood flow or perfusion after PDT.

  15. SU-D-16A-07: Photobleaching Predicts Necrosis in Interstitial PDT

    SciTech Connect

    Kim, M; Finlay, J; Liu, B; Zhu, T

    2014-06-01

    Purpose: Dosimetry for PDT has proven to be a challenge thus far, and for prediction of PDT outcome, a singlet oxygen model based on fundamental photophysical parameters has been developed. Previously, the photobleaching effect of photosensitizers was taken into account in the singlet oxygen explicit dosimetry model; here we report of direct measurements of photobleaching in the same model to assess the conditions under which implicit dosimetry using photobleaching can serve as an intermediate surrogate for PDT damage. Methods: Fluorescence spectra were measured interstitially in sensitized mouse tumors prior to after irradiation via a cylindrical diffuser. Photobleaching was determined by the relative decrease in fluorescence amplitude from the initial pre-treatment measurement. Spectra were analyzed by singular value decomposition to determine the photosensitizer concentration. Different photosensitizers were used to see the effect of photobleaching on PDT outcome and the impact of fluence on photobleaching. The drugs used were BPD (at two drug-light intervals), HPPH, and Photofrin. PDT outcome was determined by tumor necrosis radii measured upon sectioning and staining of treated tumors. Results: Post-PDT photosentizer concentrations were compared to initial pre-PDT photosensitizer concentrations, and the decrease was greater with a higher fluence measured during treatment. Furthermore, photobleaching and necrosis radius were found to be positively correlated. The relationship between photobleaching and necrosis radius is sensitizer-dependent, however the differences among sensitizers can be understood in terms of their respective photophysical parameters. Conclusions: Photobleaching is predictive of PDT outcome, but a comprehensive singlet oxygen model, has the potential to further improve the prediction of PDT outcome and the understanding of implicit dosimetry.

  16. MUON STORAGE RINGS - NEUTRINO FACTORIES

    SciTech Connect

    PARSA,Z.

    2000-05-30

    The concept of a muon storage ring based Neutrino Source (Neutrino Factory) has sparked considerable interest in the High Energy Physics community. Besides providing a first phase of a muon collider facility, it would generate more intense and well collimated neutrino beams than currently available. The BNL-AGS or some other proton driver would provide an intense proton beam that hits a target, produces pions that decay into muons. The muons must be cooled, accelerated and injected into a storage ring with a long straight section where they decay. The decays occurring in the straight sections of the ring would generate neutrino beams that could be directed to detectors located thousands of kilometers away, allowing studies of neutrino oscillations with precisions not currently accessible. For example, with the neutrino source at BNL, detectors at Soudan, Minnesota (1,715 km), and Gran Sasso, Italy (6,527 km) become very interesting possibilities. The feasibility of constructing and operating such a muon-storage-ring based Neutrino-Factory, including geotechnical questions related to building non-planar storage rings (e.g. at 8{degree} angle for BNL-Soudan, and 3{degree} angle for BNL-Gran Sasso) along with the design of the muon capture, cooling, acceleration, and storage ring for such a facility is being explored by the growing Neutrino Factory and Muon Collider Collaboration (NFMCC). The authors present overview of Neutrino Factory concept based on a muon storage ring, its components, physics opportunities, possible upgrade to a full muon collider, latest simulations of front-end, and a new bowtie-muon storage ring design.

  17. Monitoring PDT response of head and neck lesions with diffuse optical spectroscopies

    NASA Astrophysics Data System (ADS)

    Rohrbach, Daniel J.; Rigual, Nestor; Tracy, Erin; Keymel, Ken; Cooper, Michele T.; Baumann, Heinz; Henderson, Barbara W.; Sunar, Ulas

    2013-03-01

    Photodynamic therapy (PDT) has recently emerged as a potential treatment alternative for head and neck cancer. There is strong evidence that imprecise PDT dosimetry results in variations in clinical responses. Quantitative tools are likely to play an essential role in bringing PDT to a full realization of its potential benefits. They can provide standardization of site-specific individualized protocols that are used to monitor both light and photosensitizer (HPPH) dose, as well as the tissue response for individual patients. To accomplish this, we used a custom instrument and a hand-held probe that allowed quantification of blood flow, blood volume, blood oxygen saturation and drug concentration.

  18. Differential susceptibility of primary cultured human skin cells to hypericin PDT in an in vitro model.

    PubMed

    Popovic, A; Wiggins, T; Davids, L M

    2015-08-01

    Skin cancer is the most common cancer worldwide, and its incidence rate in South Africa is increasing. Photodynamic therapy (PDT) has been shown to be an effective treatment modality, through topical administration, for treatment of non-melanoma skin cancers. Our group investigates hypericin-induced PDT (HYP-PDT) for the treatment of both non-melanoma and melanoma skin cancers. However, a prerequisite for effective cancer treatments is efficient and selective targeting of the tumoral cells with minimal collateral damage to the surrounding normal cells, as it is well established that cancer therapies have bystander effects on normal cells in the body, often causing undesirable side effects. The aim of this study was to investigate the cellular and molecular effects of HYP-PDT on normal primary human keratinocytes (Kc), melanocytes (Mc) and fibroblasts (Fb) in an in vitro tissue culture model which represented both the epidermal and dermal cellular compartments of human skin. Cell viability analysis revealed a differential cytotoxic response to a range of HYP-PDT doses in all the human skin cell types, showing that Fb (LD50=1.75μM) were the most susceptible to HYP-PDT, followed by Mc (LD50=3.5μM) and Kc (LD50>4μM HYP-PDT) These results correlated with the morphological analysis which displayed distinct morphological changes in Fb and Mc, 24h post treatment with non-lethal (1μM) and lethal (3μM) doses of HYP-PDT, but the highest HYP-PDT doses had no effect on Kc morphology. Fluorescent microscopy displayed cytoplasmic localization of HYP in all the 3 skin cell types and additionally, HYP was excluded from the nuclei in all the cell types. Intracellular ROS levels measured in Fb at 3μM HYP-PDT, displayed a significant 3.8 fold (p<0.05) increase in ROS, but no significant difference in ROS levels occurred in Mc or Kc. Furthermore, 64% (p<0.005) early apoptotic Fb and 20% (p<0.05) early apoptotic Mc were evident; using fluorescence activated cell sorting (FACS), 24

  19. Search for excited and exotic muons at CDF

    SciTech Connect

    Gerberich, Heather; Hays, Christopher; Kotwal, Ashutosh; /Duke U.

    2006-05-01

    The authors present a search for the production of excited or exotic muons ({mu}*) via the reaction {bar p} + p {yields} {mu}* + {mu} {yields} {mu}{gamma}+{mu} using 371 pb{sup -1} of data collected with the Run II CDF detector. In this signature-based search, we look for a resonance in the {mu}{gamma} mass spectrum. The data are compared to standard model and detector background expectations, and with predictions of excited muon production. We use these comparisons to set limits on the {mu}* mass and compositeness scale {Lambda} in contact interaction and gauge-mediated models.

  20. Muon tracking underground

    NASA Astrophysics Data System (ADS)

    Battistoni, G.; Campana, P.; Chiarella, V.; Denni, U.; Iarocci, E.

    1986-04-01

    The design and performance of plastic streamer tubes for use in large underground particle-physics experiments such as the muon, astrophysics, and cosmic-ray observatory (MACRO) being developed for Gran Sasso Laboratory are reported. The large (1000 sq m or more) detector area required to achieve high-angular-resolution muon tracking in MACRO is covered by modules with eight 3 x 3-cm-cross section active streamer-tube cells each, similar to those used in the Mt. Blanc Laboratory detector. The MACRO modules have a maximum length of 12 m; and the cells have 60-micron-diameter wires, two conducting graphite sides, and two insulating sides (electrodeless electric-field shaping). The results of performance tests flowing 3:1 He:n-pentane through a tube module are presented graphically. Spatial resolution 1 cm and time resolution 100 ns are obtained, and the ability of the streamer tubes to detect large ionization losses with respect to the minimum is demonstrated.

  1. Clinical studies of photodynamic therapy for malignant brain tumors: Karnofsky score and neurological score in patients with recurrent gloms treated with Photofrin PDT

    NASA Astrophysics Data System (ADS)

    Muller, Paul J.; Wilson, Brian C.; Lilge, Lothar D.; Yang, Victor X.; Varma, Abhay; Bogaards, Arjen; Hetzel, Fred W.; Chen, Qun; Fullagar, Tim; Fenstermaker, Robert; Selker, Robert; Abrams, Judith

    2002-06-01

    In our previous phase II studies we treated 112 patients with malignant brain tumors with 2-mg/kg Photofrin i.v. and intra-operative cavitary PDT. We concluded that PDT was safe in patients with newly diagnosed or recurrent supratentorial malignant gliomas. Pathology, performance grade and light dose were significantly related to survival time. In selected patients when an adequate light dose was used survival time improved. The surgical mortality rate was less than 3%. [spie 2000] We have initiated two randomized prospective trials - the first, to determine if the addition of PDT to standard therapy [surgery, radiation and/or chemotherapy] prolongs the survival of patients with newly diagnosed malignant astrocytic tumors; and the second, to determine whether high light dose PDT [120 J/cm2] is superior to low light dose PDT [40 J/cm2] in patients with recurrent malignant astrocytic tumors. To date, 158 patients have been recruited - 72 to the newly diagnosed malignant glioma study and 86 to the recurrent glioma study. In the recurrent glioma study we compared the pre-operative KS and elements of the neurological examination [speech function, visual fields, cognitive function, sensory examination and gait] to the post-operative examinations at hospital discharge. The means were compared by paired student-t test. The KS in 86 of 88 patients with recurrent gliomas were assessable. The mean [s.d.] preoperative and post-operative KS were 82+/- 14 and 79+/- 17, respectively [p=0.003]. The mean decline in KS, although statistically significant, was small and of no clinical importance. The median Karnofsky score changed from 90 to 80. The KS improved in 8 patients; their post-operative average length of stay (alos) was =9.7 days. There was no change in 47 [alos=8.3], a decline of 10 points in 24 [aloc=13.4] and declined by more than 10 points in 7 [alos=23.3]. Three of these 7 patients who had a decline of >10 points improved in follow-up but did not reach their

  2. Research and Development of Future Muon Collider

    SciTech Connect

    Yonehara, K.; /Fermilab

    2012-05-01

    Muon collider is a considerable candidate of the next generation high-energy lepton collider machine. A novel accelerator technology must be developed to overcome several intrinsic issues of muon acceleration. Recent research and development of critical beam elements for a muon accelerator, especially muon beam phase space ionization cooling channel, are reviewed in this paper.

  3. Biocompatible magnetic microspheres for Use in PDT and hyperthermia.

    PubMed

    Vaccari, C B; Cerize, N N P; Morais, P C; Ré, M I; Tedesco, A C

    2012-06-01

    Loaded microspheres with a silicon (IV) phthalocyanine derivative (NzPC) acting as a photosensitizer were prepared from polyhydroxybutyrate-co-valerate (PHBHV) and poly(ecaprolactone) (PCL) polymers using the emulsification solvent evaporation method (EE). The aim of our study was to prepare two systems of these biodegradable PHBHV/PCL microspheres. The first one containing only photosensitizer previously incorporated in the PHBHV and poly(ecaprolactone) (PCL) microspheres and the second one with the post magnetization of the DDS with magnetic nanoparticles. Magnetic fluid is successfully used for controlled incorporation of nanosized magnetic particles within the micron-sized template. This is the first time that we could get a successful pos incorporation of nanosized magnetic particles in a previously-prepared polymeric template. This procedure opens a great number of possibilities of post-functionalization of polymeric micro or nanoparticles with different bioactive materials. The NzPC release profile of the systems is ideal for PDT, the zeta potential and the size particle are stable upon aging in time. In vitro studies were evaluated using gingival fibroblastic cell line. The dark citotoxicity, the phototoxicity and the AC magnetic field assays of the as-prepared nanomagnetic composite were evaluated and the cellular viability analyzed by the classical test of MTT. PMID:22905587

  4. Adjuvant photodynamic therapy (PDT) of the superficial bladder cancer

    NASA Astrophysics Data System (ADS)

    Sokolov, V. V.; Russakov, I. G.; Teplov, A. A.; Filonenko, E. V.; Ul'yanov, R. V.; Bystrov, A. A.

    2005-08-01

    Superficial transitional cell carcinoma represents 50 to 80% of newly diagnosed bladder cancer in various countries. Transurethral resection of the urinary bladder is the standard procedure for biopsy and treatment superficial bladder cancer. However recurrence tumors after transurethral resection alone is high enough (50-90%). Intravesical chemotherapy for prophylaxis after complete transurethral resection is reducing recurrence rate about 1 5%. Adjuvant intravesical Bacillus of Calmette and Guerin (BCG) is reducing recurrence rate about 30%, but frequency side effects of this therapy is very high. Purpose of this study is appreciate efficacy adjuvant PDT with photosensitizer Photogeme (Russia) of superficial bladder cancer for prophylaxis after complete transurethral resection. The follow up was from 3 to 63 months (27 months, on average). Sixty-five patients (75.6%) showed no recurrence. For the follow up period, the recurrence was revealed in 21 (24.4%) patient, in two of them it was progressing (one case of invasive growth and one case of remote metastases). Four cases of recurrence were revealed 4 months after the surgery. In other cases, the recurrence was diagnosed from 9 to 18 months.

  5. Clinical experience of PDT in Brazil: a 300 patient overview

    NASA Astrophysics Data System (ADS)

    Kurachi, Cristina; Ferreira, Juliana; Marcassa, Luis G.; Cestari Filho, Guilherme A.; Souza, Cacilda S.; Bagnato, Vanderlei S.

    2005-04-01

    Clinical application of Photodynamic Therapy (PDT) in Brazil is a result of a pioneering work in a collaborative program involving the Physics Institute and the Medical School of the University of Sao Paulo and the Amaral Carvalho Cancer Hospital in the city of Jau, Sao Paulo. This work began in 1997 with the first patient treated in 1999. Up to the end of 2003 this program has treated over 300 patients and the ones with correct follow up had their lesions included in this report. The majority of the lesions were of non-melanoma skin cancer located on the head and neck region, but the group has also treated Esophagus, Bladder, Gynecological, chest wall recurrence of breast cancer, among others. The results have shown to be compatible with internationally reported data, and we have modified some application procedures towards to a better benefit for the patient and an optimization of the results. We present the overall results observed after 5 year of experimental clinical treatment.

  6. Muon energy reconstruction in the Antarctic muon and neutrino detector array (AMANDA)

    NASA Astrophysics Data System (ADS)

    Miocinovic, Predrag

    that the energy spectrum of detected atmospheric neutrinos is consistent with its prediction. The atmospheric-neutrino energy spectrum supports the neutrino-flavor oscillation hypothesis as put forward by the Super-Kamiokande group. Based on the assumption of complete mixing (sin2 2theta = 1) and using energy spectrum shape comparison, I find that the AMANDA preferred squared mass difference is 1.6 · 10-4 eV2 ≤ Delta m2 ≤ 3.46 · 10-3 eV 2. The measurement of the atmospheric-muon energy spectrum shows a disagreement with the prediction, possibly indicating an incomplete understanding of physics that is currently used to describe atmospheric muon flux. The method presented here makes it possible to estimate energy an order of magnitude greater than was previously possible by AMANDA and it improves the resolution and accuracy over the currently used technique. It naturally scales for use in larger detectors like AMANDA- II and IceCube, and it can be easily extended for use in energy reconstruction of electron- and muon-neutrino contained events.

  7. Quasi-isochronous Muon Collection Channels

    SciTech Connect

    Yoshikawa, C.; Ankenbrandt, C.; Neuffer, D.; /Fermilab

    2010-05-01

    Intense muon beams have many potential applications, including neutrino factories and muon colliders. However, muons are produced as tertiary beams, resulting in diffuse phase space distributions. To make useful beams, the muons must be rapidly cooled before they decay. An idea conceived recently for the collection and cooling of muon beams, namely, the use of a Quasi-Isochronous Helical Channel (QIHC) to facilitate capture of muons into RF buckets, has been developed further. The resulting distribution could be cooled quickly and coalesced into a single bunch to optimize the luminosity of a muon collider. After a brief elaboration of the QIHC concept, recent developments are described.

  8. Probing beyond the Standard Model with Muons

    SciTech Connect

    Hisano, Junji

    2008-02-21

    Muon's Properties are the most precisely studied among unstable particles. After discovery of muons in 40's, the studies of muons contributed to construction and establishment of the standard model in the particle physics. Now we are going to LHC era, however, precision frontier is still important in the particle physics. In this article, we review roles of muon physics in the particle physics. Muon g-2, lepton flavor violation (LFV) in muon decay, and electric dipole moment (EDM) of muon are mainly discussed.

  9. The Gran Sasso muon puzzle

    SciTech Connect

    Fernandez-Martinez, Enrique; Mahbubani, Rakhi E-mail: rakhi@cern.ch

    2012-07-01

    We carry out a time-series analysis of the combined data from three experiments measuring the cosmic muon flux at the Gran Sasso laboratory, at a depth of 3800 m.w.e. These data, taken by the MACRO, LVD and Borexino experiments, span a period of over 20 years, and correspond to muons with a threshold energy, at sea level, of around 1.3 TeV. We compare the best-fit period and phase of the full muon data set with the combined DAMA/NaI and DAMA/LIBRA data, which spans the same time period, as a test of the hypothesis that the cosmic ray muon flux is responsible for the annual modulation detected by DAMA. We find in the muon data a large-amplitude fluctuation with a period of around one year, and a phase that is incompatible with that of the DAMA modulation at 5.2σ. Aside from this annual variation, the muon data also contains a further significant modulation with a period between 10 and 11 years and a power well above the 99.9% C.L threshold for noise, whose phase corresponds well with the solar cycle: a surprising observation for such high energy muons. We do not see this same period in the stratospheric temperature data.

  10. Muon Simulation at the Daya Bay SIte

    SciTech Connect

    Mengyun, Guan; Jun, Cao; Changgen, Yang; Yaxuan, Sun; Luk, Kam-Biu

    2006-05-23

    With a pretty good-resolution mountain profile, we simulated the underground muon background at the Daya Bay site. To get the sea-level muon flux parameterization, a modification to the standard Gaisser's formula was introduced according to the world muon data. MUSIC code was used to transport muon through the mountain rock. To deploy the simulation, first we generate a statistic sample of sea-level muon events according to the sea-level muon flux distribution formula; then calculate the slant depth of muon passing through the mountain using an interpolation method based on the digitized data of the mountain; finally transport muons through rock to get underground muon sample, from which we can get results of muon flux, mean energy, energy distribution and angular distribution.

  11. Muon Collider Task Force Report

    SciTech Connect

    Ankenbrandt, C.; Alexahin, Y.; Balbekov, V.; Barzi, E.; Bhat, C.; Broemmelsiek, D.; Bross, A.; Burov, A.; Drozhdin, A.; Finley, D.; Geer, S.; /Fermilab /Argonne /Brookhaven /Jefferson Lab /LBL, Berkeley /MUONS Inc., Batavia /UCLA /UC, Riverside /Mississippi U.

    2007-12-01

    Muon Colliders offer a possible long term path to lepton-lepton collisions at center-of-mass energies {radical}s {ge} 1 TeV. In October 2006 the Muon Collider Task Force (MCTF) proposed a program of advanced accelerator R&D aimed at developing the Muon Collider concept. The proposed R&D program was motivated by progress on Muon Collider design in general, and in particular, by new ideas that have emerged on muon cooling channel design. The scope of the proposed MCTF R&D program includes muon collider design studies, helical cooling channel design and simulation, high temperature superconducting solenoid studies, an experimental program using beams to test cooling channel RF cavities and a 6D cooling demonstration channel. The first year of MCTF activities are summarized in this report together with a brief description of the anticipated FY08 R&D activities. In its first year the MCTF has made progress on (1) Muon Collider ring studies, (2) 6D cooling channel design and simulation studies with an emphasis on the HCC scheme, (3) beam preparations for the first HPRF cavity beam test, (4) preparations for an HCC four-coil test, (5) further development of the MANX experiment ideas and studies of the muon beam possibilities at Fermilab, (6) studies of how to integrate RF into an HCC in preparation for a component development program, and (7) HTS conductor and magnet studies to prepare for an evaluation of the prospects for of an HTS high-field solenoid build for a muon cooling channel.

  12. Involvement of ASK1 activation in apoptosis induced by NPe6-PDT

    NASA Astrophysics Data System (ADS)

    Liu, Lei; Zhang, Zhen-zhen; Zhang, Zhigang

    2010-02-01

    Photodynamic therapy (PDT) employing photosensiter N-aspartyl chlorin e6 (NPe6) can induce lysosome disruption and initiate apoptotic pathway. Apoptosis signal-regulating kinase (ASK1) is an important regulator of apoptosis in response to various stresses, such as reactive oxygen species (ROS), endoplasmic reticulum (ER) stress, lipopolysaccharide (LPS) and calcium influx. In this study, we investigated the molecular mechanisms of apoptosis induced by NPe6-PDT in ASTC-a-1 cells. The results showed that the activities of ASK1 increased in response to NPe6-PDT. Over-expression of wild-type or activated mutant of ASK1 could obviously decrease cell viability and increase cell death; while inhibition of ASK1 significantly decreased cell apoptosis. These results suggested that ASK1 plays an important role in apoptosis induced by NPe6-PDT.

  13. Observations of the incidence of metastasis following laser hyperthermia in combination with chemotherapy, PDT, and excision

    NASA Astrophysics Data System (ADS)

    Wang, Mianjing; Gao, Menglin; Gao, Jin; Xue, Kexun; Xu, Zuyan; Zhang, Jingyuan; Li, Qongru; Geng, Zifan; Gong, Zhuo; Ye, Qing; Gu, Pei; Xao, Jing-Lian

    1993-03-01

    Our early observations have confirmed that laser hyperthermia or PDT alone does not promote the tumor metastasis. In order to evaluate the combined effect of local tumor laser hyperthermia on the distant metastasis, transplantable forestomach carcinoma (Fc) in 615 line mice was treated by Nd:YAG laser hyperthermia (45 degree(s)C/20 min) combined with PDT (HpD 5 mg/kg, 480 J/cm2, 20 min), chemotherapy (Cyclophosphamide 28.8 mg/kg) and excision, respectively. The results show that (1) the tumor growth inhibition by various treatment was significant compared with a control group; (2) no statistics different in metastasis rate were observed in laser hyperthermia combined with PDT, chemotherapy, or scalpel excision separately. It is suggested that laser hyperthermia combined with PDT, chemotherapy, or excision does not increase the incidence of the tumor metastasis.

  14. Preparation and Protonation of Fe2(pdt)(CNR)6, Electron-Rich Analogues of Fe2(pdt)(CO)6.

    PubMed

    Zhou, Xiaoyuan; Barton, Bryan E; Chambers, Geoffrey M; Rauchfuss, Thomas B; Arrigoni, Federica; Zampella, Giuseppe

    2016-04-01

    The complexes Fe2(pdt)(CNR)6 (pdt(2-) = CH2(CH2S(-))2) were prepared by thermal substitution of the hexacarbonyl complex with the isocyanides RNC for R = C6H4-4-OMe (1), C6H4-4-Cl (2), Me (3). These complexes represent electron-rich analogues of the parent Fe2(pdt)(CO)6. Unlike most substituted derivatives of Fe2(pdt)(CO)6, these isocyanide complexes are sterically unencumbered and have the same idealized symmetry as the parent hexacarbonyl derivatives. Like the hexacarbonyls, the stereodynamics of 1-3 involve both turnstile rotation of the Fe(CNR)3 as well as the inversion of the chair conformation of the pdt ligand. Structural studies indicate that the basal isocyanide has nonlinear CNC bonds and short Fe-C distances, indicating that they engage in stronger Fe-C π-backbonding than the apical ligands. Cyclic voltammetry reveals that these new complexes are far more reducing than the hexacarbonyls, although the redox behavior is complex. Estimated reduction potentials are E1/2 ≈ -0.6 ([2](+/0)), -0.7 ([1](+/0)), and -1.25 ([3](+/0)). According to DFT calculations, the rotated isomer of 3 is only 2.2 kcal/mol higher in energy than the crystallographically observed unrotated structure. The effects of rotated versus unrotated structure and of solvent coordination (THF, MeCN) on redox potentials were assessed computationally. These factors shift the redox couple by as much as 0.25 V, usually less. Compounds 1 and 2 protonate with strong acids to give the expected μ-hydrides [H1](+) and [H2](+). In contrast, 3 protonates with [HNEt3]BAr(F)4 (pKa(MeCN) = 18.7) to give the aminocarbyne [Fe2(pdt)(CNMe)5(μ-CN(H)Me)](+) ([3H](+)). According to NMR measurements and DFT calculations, this species adopts an unsymmetrical, rotated structure. DFT calculations further indicate that the previously described carbyne complex [Fe2(SMe)2(CO)3(PMe3)2(CCF3)](+) also adopts a rotated structure with a bridging carbyne ligand. Complex [3H](+) reversibly adds MeNC to give [Fe2(pdt

  15. Investigation of photodynamic effect caused by MPPa-PDT on breast cancer Investigation of photodynamic effect caused by MPPa-PDT

    NASA Astrophysics Data System (ADS)

    Tian, Y. Y.; Hu, X. Y.; Leung, W. N.; Yuan, H. Q.; Zhang, L. Y.; Cui, F. A.; Tian, X.

    2012-10-01

    Breast cancer is the common malignant tumor, the incidence increases with age. Photodynamic therapy (PDT) is a new technique applied in tumors, which involves the administration of a tumor localizing photosensitizer and it is followed by the activation of a specific wavelength. Pyropheophorbide-a methyl ester (MPPa), a derivative of chlorophyll, is a novel potent photosensitizer. We are exploring the photodynamic effect caused by MPPa-PDT on breast cancer. The in vitro and in vivo experiments indicate that MPPa is a comparatively ideal photosensitizer which can induce apoptosis in breast cancer.

  16. First-principles investigation of electronic structures and properties of impurities in molecular solids and semiconductors: I. Muon and muonium in organic ferromagnets. II. Erbium in silicon-optoelectronic system

    NASA Astrophysics Data System (ADS)

    Jeong, Junho

    The first-principles Hartree-Fock theory is used to obtain the electronic structures and properties of three different systems. For the TEMPO system, the trapping sites were obtained near NO group site for muonium singlet and near chlorine and bridge nitrogen for muon. The calculated hyperfine interactions including relaxation and vibrational effect were used to compare the observed zero field muSR frequency 3.2 MHz. It has been concluded that the two trapping centers that can best explain the observed muSR frequency is trapped singlet muonium near the radical oxygen and a trapped muon site near the chlorine. The direction for the easy axis is determined to be the b-axis of the monoclinic lattice and also is obtained using the magnetic moment distributions in the ferromagnetic state in the absence of muon and muonium. The nuclear quadrupole coupling constants and asymmetry parameters (eta) have studied for the 35Cl, 17O, and 14N nuclei in the TEMPO system for the bare system and systems with trapped muon and muonium. Substantial influence of the muon and muonium on the coupling constants and eta for the nuclei close to the trapping sites have been observed for the systems with trapped muon and muonium. For the beta-NPNN, the observed muSR signal at zero field with frequency 2.1 MHz is assigned to the singlet muonium sites near the two oxygens of the two NO groups and the high frequency signal ascribed to an isotropic hyperfine constant of 400MHz is assigned to the trapped muon sites near the oxygen atoms of the NO groups. Er3+-Si material which emits 1.54 mum wavelength has led to interest in optoelectronic system. Using first-principles HF procedure, the locations of Er3+ in silicon cluster without codopant were determined. Since covalent radius of Er3+ is bigger than that of silicon, the first nearest and second nearest silicon of Er3+ for Hi (Er3+Si14H18), Ti (Er3+ Si10H16, Er3+Si26H 48), and Substitutional site (Er3+Si18H 36) applied relaxation effect. The

  17. Laser-Assisted Muon Decay

    SciTech Connect

    Liu Aihua; Li Shumin; Berakdar, Jamal

    2007-06-22

    We show theoretically that the muon lifetime can be changed dramatically by embedding the decaying muon in a strong linearly polarized laser field. Evaluating the S-matrix elements taking all electronic multiphoton processes into account we find that a CO{sub 2} laser with an electric field amplitude of 10{sup 6} V cm{sup -1} results in an order of magnitude shorter lifetime of the muon. We also analyze the dependencies of the decay rate on the laser frequency and intensity.

  18. Measurement of muon intensity by Cerenkov method

    NASA Technical Reports Server (NTRS)

    Liu, Z. H.; Li, G. J.; Bai, G. Z.; Liu, J. G.; Geng, Q. X.; Ling, J.

    1985-01-01

    Optical detection is an important technique in studies and observations of air showers, muons and relevant phenomena. The muon intensity is measured in a proper energy range and to study some problems about Cerenkov radiation of cosmic rays are studied, by a muon-telescope operated with Cerenkov detector. It is found that the measured muon intensity agrees with the integral energy spectrum of cosmic ray muons.

  19. Muon front end for the neutrino factory

    NASA Astrophysics Data System (ADS)

    Rogers, C. T.; Stratakis, D.; Prior, G.; Gilardoni, S.; Neuffer, D.; Snopok, P.; Alekou, A.; Pasternak, J.

    2013-04-01

    In the neutrino factory, muons are produced by firing high-energy protons onto a target to produce pions. The pions decay to muons and pass through a capture channel known as the muon front end, before acceleration to 12.6 GeV. The muon front end comprises a variable frequency rf system for longitudinal capture and an ionization cooling channel. In this paper we detail recent improvements in the design of the muon front end.

  20. Muon ID - taking care of lower momenta muons

    SciTech Connect

    Milstene, C.; Fisk, G.; Para, A.; /Fermilab

    2005-12-01

    In the Muon package under study, the tracks are extrapolated using an algorithm which accounts for the magnetic field and the ionization (dE/dx). We improved the calculation of the field dependent term to increase the muon detection efficiency at lower momenta using a Runge-Kutta method. The muon identification and hadron separation in b-bbar jets is reported with the improved software. In the same framework, the utilization of the Kalman filter is introduced. The principle of the Kalman filter is described in some detail with the propagation matrix, with the Runge-Kutta term included, and the effect on low momenta for low momenta single muons particles is described.

  1. Lifetime-resolved photoacoustic (LPA) spectroscopy for monitoring oxygen change and photodynamic therapy (PDT)

    NASA Astrophysics Data System (ADS)

    Jo, Janggun; Lee, Chang Heon; Kopelman, Raoul; Wang, Xueding

    2016-03-01

    The Methylene Blue loaded Polyacrylamide Nanoparticles (MB-PAA NPs) are used for oxygen sensing and Photodynamic therapy (PDT), a promising therapeutic modality employed for various tumors, with distinct advantages of delivery of biomedical agents and protection from other bio-molecules overcoming inherent limitations of molecular dyes. Lifetime-resolved photoacoustic spectroscopy using quenched-phosphorescence method is applied with MB-PAA NPs so as to sense oxygen, while the same light source is used for PDT. The dye is excited by absorbing 650 nm wavelength light from a pump laser to reach triplet state. The probe laser at 810 nm wavelength is used to excite the first triplet state at certain delayed time to measure the dye lifetime which indicates oxygen concentration. The 9L cells (106 cells/ml) incubated with MB-PAA NP solution are used for monitoring oxygen level change during PDT in situ test. The oxygen level and PDT efficacy are confirmed with a commercial oximeter, and fluorescence microscope imaging and flow cytometry results. This technique with the MB-PAA NPs allowed us to demonstrate a potential non-invasive theragnostic operation, by monitoring oxygen depletion during PDT in situ, without the addition of secondary probes. Here, we demonstrate this theragnostic operation, in vitro, performing PDT while monitoring oxygen depletion. We also show the correlation between O2 depletion and cell death.

  2. Soluble guanylyl cyclase is involved in PDT-induced injury of crayfish glial cells

    NASA Astrophysics Data System (ADS)

    Kovaleva, V. D.; Uzdensky, A. B.

    2016-04-01

    Photodynamic therapy (PDT) is a potential tool for selective destruction of malignant brain tumors. However, not only malignant but also healthy neurons and glial cells may be damaged during PDT. Nitric oxide is an important modulator of cell viability and intercellular neuroglial communications. NO have been already shown to participate in PDT-induced injury of neurons and glial cells. As soluble guanylyl cyclase is the only known receptor for NO, we have studied the possible role of soluble guanylyl cyclase in the regulation of survival and death of neurons and surrounding glial cells under photo-oxidative stress induced by photodynamic treatment (PDT). The crayfish stretch receptor consisting of a single identified sensory neuron enveloped by glial cells is a simple but informative model object. It was photosensitized with alumophthalocyanine photosens (10 nM) and irradiated with a laser diode (670 nm, 0.4 W/cm2). Using inhibitory analysis we have shown that during PDT soluble guanylyl cyclase, probably, has proapoptotic and antinecrotic effect on the glial cells of the isolated crayfish stretch receptor. Proapoptotic effect of soluble guanylyl cyclase could be mediated by protein kinase G (PKG). Thus, the involvement of NO/sGC/cGMP/PKG signaling pathway in PDT-induced apoptosis of glial cells was indirectly demonstrated.

  3. EGF targeted fluorescence molecular tomography as a predictor of PDT outcomes in pancreas cancer models

    NASA Astrophysics Data System (ADS)

    Samkoe, Kimberley S.; Davis, Scott C.; Srinivasan, Subhadra; Isabelle, Martin E.; O'Hara, Julia; Hasan, Tayyaba; Pogue, Brian W.

    2010-02-01

    Verteporfin photodynamic therapy (PDT) is a promising adjuvant therapy for pancreas cancer and investigations for its use are currently underway in both orthotopic xenograft mouse models and in human clinical trials. The mouse models have been studied extensively using magnetic resonance (MR) imaging as a measure of surrogate response to verteporfin PDT and it was found that tumor lines with different levels of aggression respond with varying levels to PDT. MR imaging was successful in determining the necrotic volume caused by PDT but there was difficultly in distinguishing inflamed tissues and regions of surviving tumor. In order to understand the molecular changes within the tumor immediately post-PDT we propose the implementation of MR-guided fluorescence molecular tomography (FMT) in conjunction with an exogenously administered fluorescently labeled epidermal growth factor (EGF-IRDye800CW, LI-COR Biosciences). We have previously shown that MR-guided FMT is feasible in the mouse abdomen when multiple regions of fluorescence are considered from contributing internal organs. In this case the highly aggressive AsPC-1 (+EGFR) orthotopic tumor was implanted in SCID mice, interstitial verteporfin PDT (1mg/kg, 20J/cm) was performed when the tumor reached ~60mm3 and both tumor volume and EGF binding were followed with MR-guided FMT.

  4. Photodynamic therapy (PDT) with endoscopic ultrasound for the treatment of esophageal cancer

    NASA Astrophysics Data System (ADS)

    Woodward, Timothy A.; Wolfsen, Herbert C.

    2000-05-01

    In 1995, PDT was approved for palliative use in patients with esophageal cancer. We report our experience using PDT to treat esophageal cancer patients previously treated with combination chemotherapy and radiation therapy. In our series, nine patients referred for PDT with persistent esophageal cancer after chemo-radiation therapy. We found: (1) All patients were men with a mean age of 63 years and eight out of nine had adenocarcinoma with Barrett's esophagus; (2) All patients required endoscopic dilation after PDT; (3) At a mean follow up of 4 months, two T2N0 patients had no demonstrable tumor and all three T3N0 patients had greater than 50% tumor reduction (the partially responsive T3N0 patients will be offered repeat PDT); (4) Patients with metastatic disease (T3N1 or M1) had effective dysphagia palliation. Thus, PDT is safe and effective in ablating all or most tumor in patients with persistent esophageal cancer after chemotherapy and radiation therapy.

  5. Potentiation of ALA-PDT antitumor activity in mice using topical DMXAA

    NASA Astrophysics Data System (ADS)

    Marrero, Allison; Sunar, Ulas; Sands, Theresa; Oseroff, Allan; Bellnier, David

    2009-06-01

    Photodynamic treatment of subcutaneously implanted Colon 26 tumors in BALB/c mice using the aminolevulinic acid (ALA)-induced photosensitizer protoporphyrin IX (PpIX) was shown to be enhanced by the addition of the vascular disrupting agent 5,6-Dimethylxanthenone-4-acetic-acid (DMXAA; Novartis ASA404). DMXAA increases vascular permeability and decreases blood flow in both murine and human tumors. Sufficiently high parenteral DMXAA doses can lead to tumor collapse and necrosis. We have previously reported marked enhancement of antitumor activity when PDT, using either Photofrin or HPPH, is combined with low-dose intraperitoneal DMXAA. We now describe the first attempt to combine topically-applied DMXAA with PDT. For this, DMXAA was applied two hours before PpIX-activating light delivery. PDT with ALA-PDT alone (ALA 20%; 80 J/cm2 delivered at 75 mW/cm2) caused a 39% decrease in tumor volume compared to unirradiated controls. Addition of topical DMXAA to ALA-PDT resulted in a 74% reduction in tumor volume. Diffuse correlation spectroscopy (DCS), a non-invasive blood flow imaging method, is being used to understand the mechanism of this effect and to aid in the proper design of the therapy. For instance, our most recent DCS data suggests that the 2-hour interval between the DMXAA and light applications may not be optimum. This preliminary study suggests a potential role for topical DMXAA in combination with PDT for dermatologic tumors.

  6. Next-generation light delivery system for multitreatment extended-duration photodynamic therapy (MED-PDT)

    NASA Astrophysics Data System (ADS)

    Chen, James C.

    1997-05-01

    The primary focus of laser based oncologic PDT has been on the treatment of skin and hollow organ tumors. Extending PDT to other primary internal lesions and metastasis requires a different approach. Light Sciences has developed a series of semiconductor-based devices which will be completely implanted in the patient using established, minimally invasive surgical techniques. These devices are energized noninvasively utilizing inductive coupling. The light delivery system will allow the clinician to modulate the intensity, spatial distribution, and duration of light delivery in order to maximize the benefits derived from each PDT drug dose. Light Sciences' technology minimizes patient risk and discomfort, is cost competitive, and expands the treatment options available to the clinician. Avoidance of lengthy operations, bone marrow suppression, and an emphasis on organ preservation allow this next generation of PDT light delivery devices to be effectively integrated with other forms of cancer treatment, if desired. We have termed our technique 'Multi-treatment Extended Duration PDT'. In what follows, we shall describe Light Sciences' technology and development of minimally invasive oncologic PDT.

  7. LINACS FOR FUTURE MUON FACILITIES

    SciTech Connect

    Slawomir Bogacz, Rolland Johnson

    2008-10-01

    Future Muon Colliders (MC) and Neutrino Factories (NF) based on muon storage rings will require innovative linacs to: produce the muons, cool them, compress longi-tudinally and ‘shape’ them into a beam and finally to rap-idly accelerate them to multi-GeV (NF) and TeV (MC) energies. Each of these four linac applications has new requirements and opportunities that follow from the na-ture of the muon in that it has a short lifetime (τ = 2.2 μsec) in its own rest frame, it is produced in a tertiary process into a large emittance, and its electron, photon, and neutrino decay products can be more than an annoy-ance. As an example, for optimum performance, the linac repetition rates should scale inversely with the laboratory lifetime of the muon in its storage ring, something as high as 1 kHz for a 40 GeV Neutrino Factory or as low as 20 Hz for a 5 TeV Muon Collider. A superconducting 8 GeV Linac capable of CW operation is being studied as a ver-satile option for muon production [1] for colliders, facto-ries, and muon beams for diverse purposes. A linac filled with high pressure hydrogen gas and imbedded in strong magnetic fields has been proposed to rapidly cool muon beams [2]. Recirculating Linear Accelerators (RLA) are possible because muons do not generate significant syn-chrotron radiation even at extremely high energy and in strong magnetic fields. We will describe the present status of linacs for muon applications; in particular the longitu-dinal bunch compression in a single pass linac and multi-pass acceleration in the RLA, especially the optics and technical requirements for RLA designs, using supercon-ducting RF cavities capable of simultaneous acceleration of both μ+ and μ- species, with pulsed linac quadrupoles to allow the maximum number of passes. The design will include the optics for the multi-pass linac and droplet-shaped return arcs.

  8. Muon spin rotation in solids

    NASA Technical Reports Server (NTRS)

    Stronach, C. E.

    1983-01-01

    The muon spin rotation (MuSR) technique is used to probe the microscopic electron density in materials. High temperature MuSR and magnetization measurements in nickel are in progress to allow an unambiguous determination of the muon impurity interaction and the impurity induced change in local spin density. The first results on uniaxial stress induced frequency shifts in an Fe single crystal are also reported.

  9. Muon Colliders: The Next Frontier

    ScienceCinema

    Tourun, Yagmur [Illinois Institute of Technology, Chicago, Illinois, United States

    2010-01-08

    Muon Colliders provide a path to the energy frontier in particle physics but have been regarded to be "at least 20 years away" for 20 years. I will review recent progress in design studies and hardware R&D and show that a Muon Collider can be established as a real option for the post-LHC era if the current vigorous R&D effort revitalized by the Muon Collider Task Force at Fermilab can be supported to its conclusion. All critical technologies are being addressed and no show-stoppers have emerged. Detector backgrounds have been studied in detail and appear to be manageable and the physics can be done with existing detector technology. A muon facility can be built through a staged scenario starting from a low-energy muon source with unprecedented intensity for exquisite reach for rare processes, followed by a Neutrino Factory with ultrapure neutrino beams with unparalleled sensitivity for disentangling neutrino mixing, leading to an energy frontier Muon Collider with excellent energy resolution.

  10. Muon Colliders: The Next Frontier

    SciTech Connect

    Tourun, Yagmur

    2009-07-29

    Muon Colliders provide a path to the energy frontier in particle physics but have been regarded to be 'at least 20 years away' for 20 years. I will review recent progress in design studies and hardware R&D and show that a Muon Collider can be established as a real option for the post-LHC era if the current vigorous R&D effort revitalized by the Muon Collider Task Force at Fermilab can be supported to its conclusion. All critical technologies are being addressed and no show-stoppers have emerged. Detector backgrounds have been studied in detail and appear to be manageable and the physics can be done with existing detector technology. A muon facility can be built through a staged scenario starting from a low-energy muon source with unprecedented intensity for exquisite reach for rare processes, followed by a Neutrino Factory with ultrapure neutrino beams with unparalleled sensitivity for disentangling neutrino mixing, leading to an energy frontier Muon Collider with excellent energy resolution.

  11. Muon Colliders: The Next Frontier

    SciTech Connect

    Tourun, Yagmur

    2009-07-29

    Muon Colliders provide a path to the energy frontier in particle physics but have been regarded to be "at least 20 years away" for 20 years. I will review recent progress in design studies and hardware R&D and show that a Muon Collider can be established as a real option for the post-LHC era if the current vigorous R&D effort revitalized by the Muon Collider Task Force at Fermilab can be supported to its conclusion. All critical technologies are being addressed and no show-stoppers have emerged. Detector backgrounds have been studied in detail and appear to be manageable and the physics can be done with existing detector technology. A muon facility can be built through a staged scenario starting from a low-energy muon source with unprecedented intensity for exquisite reach for rare processes, followed by a Neutrino Factory with ultrapure neutrino beams with unparalleled sensitivity for disentangling neutrino mixing, leading to an energy frontier Muon Collider with excellent energy resolution.

  12. Effects of TOOKAD-PDT on canine prostates pre-treated with ionizing radiation

    NASA Astrophysics Data System (ADS)

    Chen, Qun; Huang, Zheng; Luck, David L.; Beckers, Jill; Trncic, Nadira; LaRue, Susan M.; Brun, Pierre-Herve; Wilson, Brian C.; Hetzel, Fred W.

    2003-06-01

    PDT in prostate cancer will likely be implemented clinically with patients who have failed prior ionizing radiation therapy (RT). The current study is to develop an in vivo model to evaluate the effects of PDT on prostatic tissue after RT. To produce a physiological and anatomical environment in prostate similar to that in patients who have failed RT, canine prostates (n=4) were subjected to a definitive course of ionizing radiation therapy (2.7 Gy x 20 fractions) 5 to 6 months prior to PDT. A laparotomy was performed to expose the prostate for PDT. Second generation photosensitizer Tookad (Palladium-Bacteriopheophorbide, Steba Biotech, The Netherlands) acts primarily on tissue vasculature and is very effective in destroying normal prostatic tissue, as shown by our prior studies. Due to the extremely fast clearance of the photosensitizer, interstitial light irradiation (760 nm, 50-200 J/cm, 150 mW/cm from a 1 cm diffuser fiber) was delivered 4 minutes after the onset of Tookad infusion (i.v. 2.5 mg/ml, 2 mg/kg, total infusion time 10 min). The prostates were harvested for histopathology one week after PDT. At one week, the lesions were characterized by acute hemorrhagic necrosis with patchy sub-capsular hyperemia and edema. The maximum lesion diameter for 50, 100 and 200 J/cm PDT was approximately 15, 20 and 28 mm, respectively. The lesion size is well correlated with light fluence and comparable to that in prostates treated with identical PDT doses but without prior-RT. Under light-microscopy, the PDT induced necrosis is clearly distinguishable from the radiation induced fibrosis. No urethral lesions were observed. Dyer"s Verhoeff stain showed the loss of stromal connective tissue and the acinar collagen in the PDT treated area. There was no noticeable damage on the bladder or underlying colon section. In conclusion, Tookad-PDT can effectively destroy prostate tissue with prior-RT induced fibrosis, thus, may provide an alternative modality for those prostate

  13. Quasi-isochronous muon collection channels

    SciTech Connect

    Ankenbrandt, Charles M.; Neuffer, David; Johnson, Rolland P.

    2015-04-26

    Intense muon beams have many potential commercial and scientific applications, ranging from low-energy investigations of the basic properties of matter using spin resonance to large energy-frontier muon colliders. However, muons originate from a tertiary process that produces a diffuse swarm. To make useful beams, the swarm must be rapidly captured and cooled before the muons decay. In this STTR project a promising new concept for the collection and cooling of muon beams to increase their intensity and reduce their emittances was investigated, namely, the use of a nearly isochronous helical cooling channel (HCC) to facilitate capture of the muons into RF bunches. The muon beam can then be cooled quickly and coalesced efficiently to optimize the luminosity of a muon collider, or could provide compressed muon beams for other applications. Optimal ways to integrate such a subsystem into the rest of a muon collection and cooling system, for collider and other applications, were developed by analysis and simulation. The application of quasi-isochronous helical cooling channels (QIHCC) for RF capture of muon beams was developed. Innovative design concepts for a channel incorporating straight solenoids, a matching section, and an HCC, including RF and absorber, were developed, and its subsystems were simulated. Additionally, a procedure that uses an HCC to combine bunches for a muon collider was invented and simulated. Difficult design aspects such as matching sections between subsystems and intensity-dependent effects were addressed. The bunch recombination procedure was developed into a complete design with 3-D simulations. Bright muon beams are needed for many commercial and scientific reasons. Potential commercial applications include low-dose radiography, muon catalyzed fusion, and the use of muon beams to screen cargo containers for homeland security. Scientific uses include low energy beams for rare process searches, muon spin resonance applications, muon beams for

  14. Explanation for the low flux of high-energy astrophysical muon neutrinos.

    PubMed

    Pakvasa, Sandip; Joshipura, Anjan; Mohanty, Subhendra

    2013-04-26

    There has been some concern about the unexpected paucity of cosmic high-energy muon neutrinos in detectors probing the energy region beyond 1 PeV. As a possible solution we consider the possibility that some exotic neutrino property is responsible for reducing the muon neutrino flux at high energies from distant sources; specifically, we consider (i) neutrino decay and (ii) neutrinos being pseudo-Dirac-particles. This would provide a mechanism for the reduction of high-energy muon events in the IceCube detector, for example. PMID:23679707

  15. ALA-PDT of glioma cell micro-clusters in BD-IX rat brain

    NASA Astrophysics Data System (ADS)

    Madsen, Steen J.; Angell-Petersen, Even; Spetalen, Signe; Carper, Stephen W.; Ziegler, Sarah A.; Hirschberg, Henry

    2006-02-01

    A significant contributory factor to the poor prognosis of patients with glioblastoma multiforme is the inability of conventional treatments to eradicate infiltrating glioma cells. A syngeneic rat brain tumor model is used to investigate the effects of aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT) on small clusters of tumor cells sequestered in normal brain. The intrinsic sensitivity of rat glioma cells to PDT was investigated by exposing ALA-incubated cells to a range of radiant exposures and irradiances using 635 nm light. Biodistribution studies were undertaken on tumor-bearing animals in order to determine the tumor selectivity of the photosensitizer following systemic administration (i.p.) of ALA. Effects of ALA-PDT on normal brain and gross tumor were evaluated using histopathology. Effects of PDT on isolated glioma cells in normal brain were investigated by treating animals 48 h after tumor cell implantation: a time when the micro-clusters of cells are protected by an intact blood-brain-barrier (BBB). Rat glioma cells in monolayer are susceptible to ALA-PDT - lower irradiances are more effective than higher ones. Fluorescence microscopy of frozen tissue sections showed that photosensitizer is produced with better than 200:1 tumor-to-normal tissue selectivity following i.p. ALA administration. ALA-PDT resulted in significant damage to both gross tumor and normal brain, however, the treatment failed to prolong survival of animals with newly implanted glioma cells compared to non-treated controls if the drug was delivered either i.p. or directly into the brain. In contrast, animals inoculated with tumor cells pre-incubated in vitro with ALA showed a significant survival advantage in response to PDT.

  16. A clinical trial testing the efficacy of PDT in preventing amputation in diabetic patients.

    PubMed

    Tardivo, João Paulo; Adami, Fernando; Correa, João Antonio; Pinhal, Maria Aparecida S; Baptista, Mauricio S

    2014-09-01

    The feet of diabetic patients continue to be an unsolved problem in medicine. Uncontrolled neuropathy, ulceration and infection usually lead to amputation and presently there is no effective and reliable method that can be used to provide an efficient cure. Overall improvement in the salvage strategies, based on comprehensive pre-clinical evaluation, debridement, antibiotic therapy and follow up, has shown improvements in certain hospital settings, but the general picture for patients with diabetic foot is to have some sort of amputation, especially in underserved populations. It is clearly necessary to develop novel treatment strategies for this worldwide health problem. Photodynamic therapy (PDT) is a treatment modality that uses light to generate in situ reactive oxygen species, which can cause cell death. PDT can be used to treat several diseases, including foot infections that do not respond well to antibiotic therapy. There are several characteristics of PDT that make it potentially ideal to treat diabetic feet: the photosensitizer is non-toxic in the dark, but after illumination it becomes a very efficient antimicrobial agent with topical use, and it can regenerate small bones, such as the phalanges. However, PDT is still not used in clinical practice to treat diabetic feet. Therefore, we decided to perform a clinical study to prove that PDT is an effective method to avoid amputation of infected diabetic feet. An inexpensive PDT protocol was developed and applied to 18 patients with osteomyelitis, classified as Grade 3 on the Wagner scale. Only one of these patients suffered amputation. At least two of them were cured from resistant bacteria strains without intravenous antibiotic therapy. In the control group of 16 patients, all of them ended up suffering amputation. The rate of amputation in the PDT group was 0.029 times the rate in the control group and the difference is clearly statistically significant (p=0.002). PMID:24814697

  17. Effect of hematoporphyrin monomethyl ether-mediated PDT on the mitochondria of canine breast cancer cells.

    PubMed

    Li, H T; Song, X Y; Yang, C; Li, Q; Tang, Damu; Tian, W R; Liu, Y

    2013-12-01

    Hematoporphyrin monomethyl ether (HMME) is a promising porphyrin-related photosensitize for photodynamic therapy (PDT). There still remains unknown changes regarding the mitochondrial in canine breast cancer cells treated with HMME-PDT. The aim of this study is to investigate the effect of HMME-PDT on structure and dysfunction of mitochondrial in cancer cells. The experimental approach included an initial study on the uptake of HMME using microscopic observation of the HMME-treated cells, optimization of the PDT-induced cell death by the MTT assay. These cells were then treated with HMME and a He-Ne laser at the wavelength of 632.8 nm following our optimized condition. Examination of mitochondrial changes by observing the stained cells under light microscope, mitochjondrial membrane potential flow cytometry, measuring the Ca(2+), SOD/GSH activity, ATPase and MDA contents for the mitochondria functions. The kinetics of HMME uptake in CHMm cells was determined and its cytocolic instead of nuclear distribution was demonstrated. The dose of 16mM HMME-PDT combined with 2.8 J/cm(2) laser irradiation was had the maximal impact on cell viability. This treatment resulted in structural changes in mitochondria that were accompanied with the loss of mitochjondrial membrane potential. As a result, HMME-PDT increased mitochondrial ROS, inhibited the enzymatic activities of mitochondrial SOD and GSH-Px, abolished mitochondrial ability in the uptake and release of calcium, and decreased mitochondrial ATPase activity. The combination of these abnormalities led to accumulation of ROS in mitochondrial to high levels, which in turn contributed to HMME-PDT-induced damages of mitochondrial structure and mitochondrial dysfunction. PMID:24284094

  18. In vitro therapeutic effect of PDT combined with VEGF-A gene therapy

    NASA Astrophysics Data System (ADS)

    Lecaros, Rumwald Leo G.; Huang, Leaf; Hsu, Yih-Chih

    2014-02-01

    Vascular endothelial growth factor A (VEGF-A), commonly known as VEGF, is one of the primary factors that affect tumor angiogenesis. It was found to be expressed in cancer cell lines including oral squamous cell carcinoma. Photodynamic therapy (PDT) is a novel therapeutic modality to treat cancer by using a photosensitizer which is activated by a light source to produce reactive oxygen species and mediates oxygen-independent hypoxic conditions to tumor. Another emerging treatment to cure cancer is the use of interference RNA (e.g. siRNA) to silence a specific mRNA sequence. VEGF-A was found to be expressed in oral squamous cell carcinoma and overexpressed after 24 hour post-PDT by Western blot analysis. Cell viability was found to decrease at 25 nM of transfected VEGF-A siRNA. In vitro combined therapy of PDT and VEGF-A siRNA showed better response as compared with PDT and gene therapy alone. The results suggest that PDT combined with targeted gene therapy has a potential mean to achieve better therapeutic outcome.

  19. Interleukin-12 reverses the inhibitory impact of photodynamic therapy (PDT) on the murine contact hypersensitivity response

    NASA Astrophysics Data System (ADS)

    Simkin, Guillermo O.; Levy, Julia G.; Hunt, David W. C.

    1998-05-01

    Treatment of mice with certain photosensitizers combined with exposure to visible light limits the development of the immunologically-mediated contact hypersensitivity (CHS) response against topically-applied chemical haptens. Understanding of the inhibitory action of photosensitizers upon the CHS response is incomplete. Benzoporphyrin derivative monoacid ring A (BPD-MA, verteporfin), a photosensitizer with immunomodulatory activity, strongly depressed CHS responses to the hapten dinitrofluorobenzene (DNFB). However, if mice were administered 1 (mu) g of a recombinant preparation of the pro- inflammatory cytokine interleukin-12 (rIL-12), full-fledged CHS responses to DNFB ensued in animals treated with BPD-MA and light. In contrast, when rIL-12 was given in combination with an anti-IL-12 antibody the restorative effect of rIL-12 on the CHS response of PDT-treated mice was blocked. Evaluation of the cytokine status of spleen and draining lymph node cells showed for DNFB painted animals, that the release of the immunosuppressive cytokine IL-10 was increased by PDT and rIL-12 counter-acted the increase in IL-10 liberation associated with PDT. These studies indicate that IL-10 formation is upregulated and the availability of IL-12 may be limited in mice treated with PDT. These features may contribute to deficient CHS responses observed with PDT.

  20. Double-targeting Using A TrkC-Ligand Conjugated To BODIPY-based PDT Agent

    PubMed Central

    Kamkaew, Anyanee; Burgess, Kevin

    2013-01-01

    A molecule 1 (IY-IY-PDT) was designed to contain a fragment (IY-IY) that targets the TrkC receptor, and a photosensitizer that acts as an agent for photodynamic therapy (PDT). Molecule 1 had sub-micromolar photocytotoxicities to cells that were either engineered to stably express TrkC (NIH3T3-TrkC) or that naturally express high levels of TrkC (SY5Y neuroblastoma lines). Control experiments showed 1 is not cytotoxic in the dark, and has significantly less photocytotoxicity towards cells that do not express TrkC (NIH3T3-WT). Other controls featuring a similar agent 2 (YI-YI-PDT) which is identical and isomeric with 1 except that the targeting region is scrambled (a YI-YI motif, see text) showed 1 is considerably more photocytotoxic than 2 on TrkC+ cells. Imaging live TrkC+ cells after treatment with a fluorescent agent 1 (IY-IY-PDT) proved that 1 permeates into TrkC+ cells and localizes in the lysosomes. This observation indirectly indicates agent 1 enters the cells via the TrkC receptor. Consistent with this, the dose-dependent PDT effects of 1 can be competitively reduced by the natural TrkC ligand, neurotrophin NT3. PMID:24063347

  1. Our experience of PDT of cancer with two Russian-produced photosensitizers

    NASA Astrophysics Data System (ADS)

    Stranadko, Eugeny P.; Skobelkin, Oleg K.

    1995-05-01

    Analysis of the results of photodynamic therapy (PDT) for treating malignant neoplasms of the skin, mammary glands, tongue, oral mucous, lower lip, larynx, lungs, urinary bladder, rectum,and other locations has been made. During 1992-1994 432 tumoral foci in 108 patients have been treated with PDT. All patients were previously treated with conventional techniques without effect or they were not treated due to contraindications either because of sever accompanying diseases or because of old age. A number of the patients had PDT because of recurrences or intradermal metastases within one to two years after surgical, radial, or combined treatment. Two homemade preparations were used as photosensitizers: Photohem (hematoporphyrin derivative) and Photosense (aluminum sulfonated phthalocyanine). Light sources were an American dye laser with argon laser pumping and homemade laser devices including a copper vapor laser-pumped dye laser, gas discharge unit, gold vapor laser for the Photohem sessions, wile for the Photosense sessions were used solid state lasers on yttrium aluminate. Up to now we have follow-up control data within 2 months and 3 years. Positive effect of PDT was seen in 90.7% of patients including complete regression of tumors in 52% and partial in 38.7%. Currently this new technique of treating malignant neoplasms is successfully being used in Russia; new photosensitizers and light sources for PDT and fluorescent tumor diagnostics are being developed as well.

  2. Muon-muon and other high energy colliders

    SciTech Connect

    Palmer, R.B.; Gallardo, J.C.

    1997-02-01

    The first section looks at the high energy physics advantages, disadvantages and luminosity requirements of hadron, of lepton and photon-photon colliders for comparison. The second section discusses the physics considerations for the muon collider. The third section covers muon collider components. The fourth section is about the intersection region and detectors. In the fifth section, the authors discuss modifications to enhance the muon polarization`s operating parameters with very small momentum spreads, operations at energies other than the maximum for which the machine is designed, and designs of machines for different maximum energies. The final section discusses a Research and Development plan aimed at the operation of a 0.5 TeV demonstration machine by the year 2010, and of the 4 TeV machine by the year 2020.

  3. Muon motion in titanium hydride

    NASA Technical Reports Server (NTRS)

    Kempton, J. R.; Petzinger, K. G.; Kossler, W. J.; Schone, H. E.; Hitti, B. S.; Stronach, C. E.; Adu, N.; Lankford, W. F.; Reilly, J. J.; Seymour, E. F. W.

    1988-01-01

    Motional narrowing of the transverse-field muon spin rotation signal was observed in gamma-TiH(x) for x = 1.83, 1.97, and 1.99. An analysis of the data for TiH1.99 near room temperature indicates that the mechanism responsible for the motion of the muon out of the octahedral site is thermally activated diffusion with an attempt frequency comparable to the optical vibrations of the lattice. Monte Carlo calculations to simulate the effect of muon and proton motion upon the muon field-correlation time were used to interpret the motional narrowing in TiH1.97 near 500 K. The interpretation is dependent upon whether the Bloembergen, Purcell, and Pound (BPP) theory or an independent spin-pair relaxation model is used to obtain the vacancy jump rate from proton NMR T1 measurements. Use of BPP theory shows that the field-correction time can be obtained if the rate of motion of the muon with respect to the rate of the motion for the protons is decreased. An independent spin-pair relaxation model indicates that the field-correlation time can be obtained if the rate of motion for the nearest-neighbor protons is decreased.

  4. Muon-Pair Production by Atmospheric Muons in CosmoALEPH

    SciTech Connect

    Maciuc, F.; Grupen, C.; Hashim, N.O.; Luitz, S.; Mailov, A.; Muller, A.S.; Putzer, A.; Sander, H.G.; Schmeling, S.; Schmelling, M.; Tcaciuc, R.; Wachsmuth, H.; Ziegler, T.; Zuber, K.; /Heidelberg, Max Planck Inst. /Siegen U. /SLAC /Karlsruhe, Forschungszentrum /Heidelberg U. /Mainz U., Inst. Phys. /CERN /Princeton U. /Oxford U.

    2006-03-06

    Data from a dedicated cosmic ray run of the ALEPH detector were used in a study of muon trident production, i.e., muon pairs produced by muons. Here the overburden and the calorimeters are the target materials while the ALEPH time projection chamber provides the momentum measurements. A theoretical estimate of the muon trident cross section is obtained by developing a Monte Carlo simulation for muon propagation in the overburden and the detector. Two muon trident candidates were found to match the expected theoretical pattern. The observed production rate implies that the nuclear form factor cannot be neglected for muon tridents.

  5. Muon collider interaction region design

    SciTech Connect

    Alexahin, Y.I.; Gianfelice-Wendt, E.; Kashikhin, V.V.; Mokhov, N.V.; Zlobin, A.V.; Alexakhin, V.Y.; /Dubna, JINR

    2010-05-01

    Design of a muon collider interaction region (IR) presents a number of challenges arising from low {beta}* < 1 cm, correspondingly large beta-function values and beam sizes at IR magnets, as well as the necessity to protect superconducting magnets and collider detectors from muon decay products. As a consequence, the designs of the IR optics, magnets and machine-detector interface are strongly interlaced and iterative. A consistent solution for the 1.5 TeV c.o.m. muon collider IR is presented. It can provide an average luminosity of 10{sup 34} cm{sup -2}s{sup -1} with an adequate protection of magnet and detector components.

  6. Law of Conservation of Muons

    DOE R&D Accomplishments Database

    Feinberg, G.; Weinberg, S.

    1961-02-01

    A multiplicative selection rule for mu meson-electron transitions is proposed. A "muon parity" = -1 is considered for the muon and its neutrino, while the "muon parity" for all other particles is +1. The selection rule then states that (-1) exp(no. of initial (-1) parity particles) = (-1) exp(no. of final (-1) parity particles). Several reactions that are forbidden by an additive law but allowed by the multiplicative law are suggested; these reactions include mu{sup +} .> e{sup +} + nu{sub mu} + {ovr nu}{sub e}, e{sup -} + e{sup -} .> mu{sup -} + mu{sup -}, and muonium .> antimuonium (mu{sup +} + e{sup -} .> mu{sup -} + e{sup +}). An intermediate-boson hypothesis is suggested. (T.F.H.)

  7. The MICE Muon Beam Line

    SciTech Connect

    Apollonio, Marco

    2011-10-06

    In the Muon Ionization Cooling Experiment (MICE) at RAL, muons are produced and transported in a dedicated beam line connecting the production point (target) to the cooling channel. We discuss the main features of the beamline, meant to provide muons with momenta between 140 MeV/c and 240 MeV/c and emittances up to 10 mm rad, which is accomplished by means of a diffuser. Matching procedures to the MICE cooling channel are also described. In summer 2010 we performed an intense data taking campaign to finalize the calibration of the MICE Particle Identification (PID) detectors and the understanding of the beam line, which completes the STEPI phase of MICE. We highlight the main results from these data.

  8. Cell cycle arrest induced by MPPa-PDT in MDA-MB-231 cells

    NASA Astrophysics Data System (ADS)

    Liang, Liming; Bi, Wenxiang; Tian, Yuanyuan

    2016-05-01

    Photodynamic therapy (PDT) is a medical treatment using a photosensitizing agent and light source to treat cancers. Pyropheophorbidea methyl ester (MPPa), a derivative of chlorophyll, is a novel potent photosensitizer. To learn more about this photosensitizer, we examined the cell cycle arrest in MDA-MB-231. Cell cycle and apoptosis were measured by flow cytometer. Checkpoints of the cell cycle were measured by western blot. In this study, we found that the expression of Cyclin D1 was obviously decreased, while the expression of Chk2 and P21 was increased after PDT treatment. This study showed that MPPa-PDT affected the checkpoints of the cell cycle and led the cells to apoptosis.

  9. Advances in the understanding of host response associated with tumor PDT

    NASA Astrophysics Data System (ADS)

    Korbelik, Mladen

    2007-02-01

    Photodynamic therapy (PDT) is clinically established modality used for treatment of solid cancers and other conditions, which destroys lesions by localized generation of cytotoxic oxygen species mediated by administered drugs (photosensitizers) that are activated at targeted sites by exposure to light. Since over 20 years ago it has become increasingly clear that important contribution to the antitumor effect of PDT is secured by host reaction induced by this therapy and manifested as inflammatory and immune response. Presented is an overview of advances in the understanding of this host response associated with tumor PDT by tracing its evolution from initial breakthroughs and discoveries in the early 1980s, followed by advances preceding recent developments, and concluding with recently acquired knowledge and directions for clinical exploitation. Tribute is given to researchers making important contributions to this field during the last three decades including Drs. Gianfranco Canti, Julia Levy, and Barbara Henderson.

  10. Glucose-functionalized amino-OPEs as biocompatible photosensitizers in PDT.

    PubMed

    Deni, Elisa; Zamarrón, Alicia; Bonaccorsi, Paola; Carmen Carreño, M; Juarranz, Ángeles; Puntoriero, Fausto; Sciortino, Maria Teresa; Ribagorda, María; Barattucci, Anna

    2016-03-23

    Photodynamic therapy (PDT) is a minimally invasive procedure that can provide a selective eradication of neoplastic diseases by the combined effect of a photosensitizer, light and oxygen. New amino oligo(phenylene-ethynylene)s (OPEs), bearing hydrophilic glucoside terminations, have been prepared, characterized and tested as photosensitizers in PDT. The effectiveness of these compounds in combination with UVA light has been checked on two tumor cell lines (HEp-2 and HeLa cells, derived from a larynx carcinoma and a cervical carcinoma, respectively). The compounds triggered a mitotic blockage that led to the cell death, being the effect active up to 3 μm concentration. The photophysical properties of OPEs, such as high quantum yield, stability, singlet oxygen production, biocompatibility, easy cell-internalization and very good response even at low concentration, make them promising photosensitizers in the application of PDT. PMID:26854378

  11. MICE: The International Muon Ionization Cooling Experiment

    SciTech Connect

    Kaplan, Daniel M.

    2006-03-20

    Ionization cooling of a muon beam is a key technique for a Neutrino Factory or Muon Collider. An international collaboration is mounting an experiment to demonstrate muon ionization cooling at the Rutherford Appleton Laboratory. We aim to complete the experiment by 2010.

  12. A Highly intense DC muon source, MuSIC and muon CLFV search

    NASA Astrophysics Data System (ADS)

    Hino, Y.; Kuno, Y.; Sato, A.; Sakamoto, H.; Matsumoto, Y.; Tran, N. H.; Hashim, I. H.; Fukuda, M.; Hayashida, Y.; Ogitsu, T.; Yamamoto, A.; Yoshida, M.

    2014-08-01

    MuSIC is a new muon facility, which provides the world's highest intense muon beam with continuous time structure at Research Center of Nuclear Physics (RCNP), Osaka University. It's intensity is designed to be 108 muons per second with only 0.4 kW proton beam. Such a high intense muon beam is very important for searches of rare decay processes, for example search for the muon to electron conversion.

  13. ALA PDT for high grade dysplasia in Barrett's oesophagus: review of a decade's experience

    NASA Astrophysics Data System (ADS)

    Bown, Stephen G.; Mackenzie, Gary D.; Dunn, Jason M.; Thorpe, Sally M.; Lovat, Laurence B.

    2009-06-01

    We have been investigating PDT with 5 aminolaevulinic acid (ALA) for the treatment of high grade dysplasia (HGD) in Barrett's oesophagus (BO) for over a decade. This drug has inherent advantages over porfimer sodium (Photofrin), the current approved photosensitiser in the UK and USA, which causes strictures in 18-50% and light sensitivity for up to three months. ALA has a lower rate of oesophageal strictures due to its preferential activity in the mucosa, sparing the underlying muscle, and patients are only light sensitive for 1-2 days. Within a randomised controlled trial, we demonstrated that an ALA dose of 60mg/kg activated by 1000J/cm red laser light is the most effective. Using these values we achieved complete reversal of HGD at 1 year in 89% of 27 patients. A randomised controlled trial of ALA vs porfimer sodium PDT for HGD is currently under way with end points of efficacy and safety. 50 of 66 patients have been recruited. Preliminary data suggest ALA PDT is safer with a trend to higher efficacy. Late relapse can occur in 20% of patients. New prognostic markers, in particular aneuploidy, are helping us to identify and target patients at risk of late relapse. Furthermore optical biopsy techniques such as elastic scattering spectroscopy (ESS) may allow detection of nuclear abnormalities in vivo and enable us to target areas of interest whilst reducing sampling error. PDT faces new challenges for the treatment of HGD in BO, with the recent introduction of balloon based radiofrequency ablation. This technique appears simpler and as effective as PDT, but follow up is currently short and long term safety data is lacking. In our experience ALA PDT is currently the most effective minimally invasive treatment for HGD in BO. This work was undertaken at UCLH/UCL who received a proportion of funding from the Department of Health's NIHR Biomedical Research Centres funding scheme.

  14. Contribution of the nos-pdt operon to virulence phenotypes in methicillin-sensitive Staphylococcus aureus.

    PubMed

    Sapp, April M; Mogen, Austin B; Almand, Erin A; Rivera, Frances E; Shaw, Lindsey N; Richardson, Anthony R; Rice, Kelly C

    2014-01-01

    Nitric oxide (NO) is emerging as an important regulator of bacterial stress resistance, biofilm development, and virulence. One potential source of endogenous NO production in the pathogen Staphylococcus aureus is its NO-synthase (saNOS) enzyme, encoded by the nos gene. Although a role for saNOS in oxidative stress resistance, antibiotic resistance, and virulence has been recently-described, insights into the regulation of nos expression and saNOS enzyme activity remain elusive. To this end, transcriptional analysis of the nos gene in S. aureus strain UAMS-1 was performed, which revealed that nos expression increases during low-oxygen growth and is growth-phase dependent. Furthermore, nos is co-transcribed with a downstream gene, designated pdt, which encodes a prephenate dehydratase (PDT) enzyme involved in phenylalanine biosynthesis. Deletion of pdt significantly impaired the ability of UAMS-1 to grow in chemically-defined media lacking phenylalanine, confirming the function of this enzyme. Bioinformatics analysis revealed that the operon organization of nos-pdt appears to be unique to the staphylococci. As described for other S. aureus nos mutants, inactivation of nos in UAMS-1 conferred sensitivity to oxidative stress, while deletion of pdt did not affect this phenotype. The nos mutant also displayed reduced virulence in a murine sepsis infection model, and increased carotenoid pigmentation when cultured on agar plates, both previously-undescribed nos mutant phenotypes. Utilizing the fluorescent stain 4-Amino-5-Methylamino-2',7'-Difluorofluorescein (DAF-FM) diacetate, decreased levels of intracellular NO/reactive nitrogen species (RNS) were detected in the nos mutant on agar plates. These results reinforce the important role of saNOS in S. aureus physiology and virulence, and have identified an in vitro growth condition under which saNOS activity appears to be upregulated. However, the significance of the operon organization of nos-pdt and potential

  15. Photofrin-PDT for gastric cancer in the era of endoscopic submucosal dissection

    NASA Astrophysics Data System (ADS)

    Nishiwaki, Yoshiro; Ikematsu, Yoshito; Tokunaga, Yuuji; Kanai, Toshikazu

    2009-06-01

    Background: Endoscopic mucosal resection (EMR) was originated to treat early gastric cancer (EGC). EMR was suitable for small, mucosal and well-differentiated adenocarcinoma without ulceration. It was difficult to resect larger tumors en bloc by this method. In recent years, a more useful method, endoscopic submuscosal dissection (ESD) has been developed, which enables en bloc resection of large mucosal lesions. On the contrary, photodynamic therapy (PDT) is applicable to submucosal, poorly differentiated, or carcinoma with ulceration. In the era of ESD, we evaluated the value of Photofrin-PDT. Patients & Methods: We applied PDT to 36 patients including three advanced cancers, who had been excluded from EMR (ESD) and were at high risks for surgery or refused surgery. Four EGC patients who had not been cured by EMR (ESD) were included. Our PDT procedure consisted of polyhematoporphyrin ether/ester administration (Photofrin, 2 mg/Kg) and pulsed excimer dye laser irradiation at 630 nm 48 hours (and 96 hours) after sensitization. Results: Complete response (CR) at three months was obtained in 84% (21/25) of mucosal cancer and in 50% (4/8) of submucosal cancer. Although three patients with an advanced cancer improved but were not cured, quality of their life was maintained. There were no serious side effects except skin photosensitivity. Conclusion: Photofrin-PDT should be applied not only EGC patients who are excluded from ESD and have not been cured by ESD with poor risk for surgery, and have high possibilitiy to be cured by PDT, but also advanced cancer patients for local improvement of lesions.

  16. Contribution of the nos-pdt Operon to Virulence Phenotypes in Methicillin-Sensitive Staphylococcus aureus

    PubMed Central

    Almand, Erin A.; Rivera, Frances E.; Shaw, Lindsey N.; Richardson, Anthony R.; Rice, Kelly C.

    2014-01-01

    Nitric oxide (NO) is emerging as an important regulator of bacterial stress resistance, biofilm development, and virulence. One potential source of endogenous NO production in the pathogen Staphylococcus aureus is its NO-synthase (saNOS) enzyme, encoded by the nos gene. Although a role for saNOS in oxidative stress resistance, antibiotic resistance, and virulence has been recently-described, insights into the regulation of nos expression and saNOS enzyme activity remain elusive. To this end, transcriptional analysis of the nos gene in S. aureus strain UAMS-1 was performed, which revealed that nos expression increases during low-oxygen growth and is growth-phase dependent. Furthermore, nos is co-transcribed with a downstream gene, designated pdt, which encodes a prephenate dehydratase (PDT) enzyme involved in phenylalanine biosynthesis. Deletion of pdt significantly impaired the ability of UAMS-1 to grow in chemically-defined media lacking phenylalanine, confirming the function of this enzyme. Bioinformatics analysis revealed that the operon organization of nos-pdt appears to be unique to the staphylococci. As described for other S. aureus nos mutants, inactivation of nos in UAMS-1 conferred sensitivity to oxidative stress, while deletion of pdt did not affect this phenotype. The nos mutant also displayed reduced virulence in a murine sepsis infection model, and increased carotenoid pigmentation when cultured on agar plates, both previously-undescribed nos mutant phenotypes. Utilizing the fluorescent stain 4-Amino-5-Methylamino-2',7'-Difluorofluorescein (DAF-FM) diacetate, decreased levels of intracellular NO/reactive nitrogen species (RNS) were detected in the nos mutant on agar plates. These results reinforce the important role of saNOS in S. aureus physiology and virulence, and have identified an in vitro growth condition under which saNOS activity appears to be upregulated. However, the significance of the operon organization of nos-pdt and potential

  17. Feasibility of repeated sequential treatments of RIF-1 tumors with photodynamic therapy (PDT) using lutetium texaphyrin (PCI-0123)

    NASA Astrophysics Data System (ADS)

    Miles, Dale R.; Parker, Lynn M.; Thiemann, Patricia A.; Woodburn, Kathryn W.; Young, Stuart W.

    1997-05-01

    Lutetium texaphyrin (PCI-0123) is currently in clinical trials as a PDT agent for the treatment of cancer patients. The drug is cleared rapidly from the plasma, and photoirradiation can be performed shortly after drug administration.T He photosensitizer as yet does not appear to elicit any significant skin photosensitivity. These characteristics favor frequent multiple PDT treatments with PCI-0123. In order to support repeated PDT treatments in the clinic, the safety of multiple drug dosing was studied in rats and mice. In rats, each group received 5 consecutive daily intravenous administrations of 5, 15, 30, or 60 mg/kg/day of PCI-0123. There were no deaths in any of the groups, and no drug-related effects were detected in the 5 mg/kg/day group. In mice, there were no observable signs of toxicity after consecutive daily administration of 10 micrometers ol/kg/day of PCI-0123 for 13 days. The feasibility and efficacy of repeated PDT treatments were assessed in C3H mice bearing RIF-1 tumors. Repeated PDT proved to be superior to a single PDT treatment. Repeated PDT treatments were well tolerated. Seven PDT treatments were administered over a nine day period without significant toxicity while achieving good therapeutic responses. All six groups receiving repeated PDT treatments showed an improved response compared to groups receiving a single PDT cycle, and the improvement was statistically significant for five of these groups. Sixty-two percent of mice receiving four sequential daily treatments were cured, and daily treatments were superior to regimens with longer intervals between PDT cycles.

  18. Light fractionation increases the efficacy of ALA-PDT but not of MAL-PDT: What is the role of (vascular) endothelial cells?

    NASA Astrophysics Data System (ADS)

    de Bruijn, H. S.; de Vijlder, H. C.; de Haas, E. R. M.; van der Ploeg-van den Heuvel, A.; Kruijt, B.; Poel-Dirks, D.; Sterenborg, H. J. C. M.; ten Hagen, T. L. M.; Robinson, D. J.

    2009-06-01

    Photodynamic therapy (PDT) using protoporpyrin IX (PpIX) precursors like 5-aminolevulinic acid (ALA) or methyl-aminolevulinate (MAL) has shown to be effective in the treatment of various skin diseases. Using ALA we have shown in numerous studies a significantly improved efficacy by applying light fractionation with a long dark interval. In contrast, in the hairless mouse model, the PDT efficacy using MAL is unaffected by adopting this approach. More acute edema is found after ALA-PDT suggesting a difference in response of endothelial cells to PDT. To investigate the role of endothelial cells, cryo-sections of hairless mouse skin after 4 hours of topical MAL or ALA application were stained with a fluorescent endothelial cell marker (CD31). Co-localization of this marker with the PpIX fluorescence was performed using the spectral imaging function of the confocal microscope. We have also used intra-vital confocal microscopy to image the PpIX fluorescence distribution in correlation with the vasculature of live mouse skin. Our results show PpIX fluorescence at depth in cryo-sections of mouse skin after 4 hours of topical application. Co-localization has shown to be difficult due to the changes in tissue organization caused by the staining procedure. As expected we found high PpIX fluorescence levels in the epidermis after both MAL and ALA application using intra-vital microscopy. After ALA application more PpIX fluorescence was found deep in the dermal layer of the skin than after MAL. Furthermore we detected localized fluorescence in unidentified structures that could not be correlated to blood vessels or nerves.

  19. Endoscopic treatment of early bronchial cancer: our experience with photodynamic therapy (PDT)

    NASA Astrophysics Data System (ADS)

    Corti, Luigi; Toniolo, Lamberto; Boso, Caterina; Colaut, Flavio; Fiore, Davide; Muzzio, Pier-Carlo; Loreggian, Lucio; Sotti, Guido

    2009-06-01

    The role of photodynamic therapy (PDT) in the treatment of small cancers has been established in several clinical studies. Here, we report on the efficacy of PDT for early inoperable or recurrent non-small-cell lung cancer (NSCLC). Methods and Materials: From June 1989 to November 2004, 40 patients with 50 NSCLC were treated with PDT. Twelve cases were inoperable for medical reasons and were staged as T1N0M0, and 28 had recurrent in situ carcinoma. Patients with residual disease after PDT received definitive radiotherapy and/or brachytherapy. Follow-up ranged from 6 to 167 months (median 43.59). Twenty of the 40 patients received i.v. injections of hematoporphyrin derivative (5 mg/kg), the other 20 had injections of porfimer sodium (Photofrin, 2 mg/kg). An argon dye laser (630 nm wavelength, 200-300 J/cm2) was used for light irradiation in 24 of the 40 patients, a diode laser (Diomed, 630 nm wavelength, 100- 200 J/cm2) in the other 16. Results: PDT obtained a 72% complete response (CR) rate (36/50 treated lesions), that is 27 CR among the 37 Tis carcinomas and 9 among the 13 T1 cases. Kaplan-Meier curves showed a mean overall survival (OS) of 75.59 months (median 91.4 months). Two- and 5- year OS rates were 72.78% and 59.55%. The mean and median survival rates for patients with Tis stage were 86.5 and 120.4 months, respectively (standard error 9.50) and for patients with T1 disease they were 45.78 and 35.71 months, respectively; the difference was statistically significant (P< 0.03). No severe early or late PDT-related adverse events were recorded. Conclusions: PDT is effective in early primary or recurrent NSCLC, resulting in a CR rate of 72%. The incorporation of PDT in standard clinical practice, in combination with radiotherapy, warrants further investigation.

  20. A method for video-assisted thoracoscopic photodynamic therapy (VAT-PDT).

    PubMed

    Moghissi, Keyvan; Dixon, Kate; Thorpe, J Andrew C

    2003-09-01

    A technique is described for application of photodynamic therapy (PDT) to peripheral pulmonary and other intrathoracic malignant tumours. For video-assisted thoracoscopic-PDT we advocate the use of the flexible fibreoptic bronchoscope through an appropriately placed port. This, together with the standard thoracoscope and attached monitor can provide three-dimensional visualisation of the intrathoracic lesion and more importantly allow the accurate delivery of laser light to the tumour. At the present time we have successfully used this method without complication in three patients with advanced inoperable disease. PMID:17670074

  1. Synthesis, characterization and preclinical studies of two-photon-activated targeted PDT therapeutic triads

    NASA Astrophysics Data System (ADS)

    Spangler, C. W.; Starkey, J. R.; Rebane, A.; Meng, F.; Gong, A.; Drobizhev, M.

    2006-02-01

    Photodynamic therapy (PDT) continues to evolve into a mature clinical treatment of a variety of cancer types as well as age-related macular degeneration of the eye. However, there are still aspects of PDT that need to be improved in order for greater clinical acceptance. While a number of new PDT photo-sensitizers, sometimes referred to as second- or third- generation therapeutic agents, are currently under clinical investigation, the direct treatment through the skin of subcutaneous tumors deeper than 5 mm remains problematic. Currently approved PDT porphyrin photo-sensitizers, as well as several modified porphyrins (e.g. chlorins, bacteriochlorins, etc.) that are under clinical investigation can be activated at 630-730 nm, but none above 800 nm. It would be highly desirable if new PDT paradigms could be developed that would allow photo-activation deep in the tissue transparency window in the Near-infrared (NIR) above 800 nm to reduce scattering and absorption phenomena that reduce deep tissue PDT efficacy. Rasiris and MPA Technologies have developed new porphyrins that have greatly enhanced two-photon absorption ( P A ) cross-sections and can be activated deep in the NIR (ca. 780-850 nm). These porphyrins can be incorporated into a therapeutic triad that also employs an small molecule targeting agent that directs the triad to over-expressed tumor receptor sites, and a NIR onephoton imaging agent that allows tracking the delivery of the triad to the tumor site, as well as clearance of excess triad from healthy tissue prior to the start of PDT treatment. We are currently using these new triads in efficacy studies with a breast cancer cell line that has been transfected with luciferase genes that allow implanted tumor growth and post- PDT treatment efficacy studies in SCID mouse models by following the rise and decay of the bioluminescence signal. We have also designed highly absorbing and scattering collagen breast cancer phantoms in which we have demonstrated

  2. Physics with a millimole of muons

    SciTech Connect

    Quigg, C.

    1998-03-01

    The eventual prospect of muon colliders reaching several TeV encourages us to consider the experimental opportunities presented by very copious stores of muons, approaching 10{sup 21} per year. I summarize and comment upon some highlights of the Fermilab Workshop on Physics at the First Muon Collider and at the Front End of a Muon Collider. Topics include various varieties of {mu}{mu} colliders, {mu}p colliders, and applications of the intense neutrino beams that can be generated in muon storage rings.

  3. Superconducting magnet system for muon beam cooling

    SciTech Connect

    Andreev, N.; Johnson, R.P.; Kashikhin, V.S.; Kashikhin, V.V.; Novitski, I.; Yonehara, K.; Zlobin, A.; /Fermilab

    2006-08-01

    A helical cooling channel has been proposed to quickly reduce the six-dimensional phase space of muon beams for muon colliders, neutrino factories, and intense muon sources. A novel superconducting magnet system for a muon beam cooling experiment is being designed at Fermilab. The inner volume of the cooling channel is filled with liquid helium where passing muon beam can be decelerated and cooled in a process of ionization energy loss. The magnet parameters are optimized to match the momentum of the beam as it slows down. The results of 3D magnetic analysis for two designs of magnet system, mechanical and quench protection considerations are discussed.

  4. Combination of PI3K/Akt/mTOR inhibitors and PDT in endothelial and tumor cells

    NASA Astrophysics Data System (ADS)

    Fateye, Babasola; Chen, Bin

    2011-02-01

    The PI3/Akt/mTOR kinase signaling pathway is a major signaling pathway in eukaryotic cells, and dysregulation of this signaling pathway has been implicated in tumorigenesis and malignancy in several cancers including prostate cancer. We assessed the effects of combination PI3K pathway inhibition on the efficacy of PDT in human prostate tumor cell line (PC3) and SV40-transformed mouse endothelial cell line (SVEC-40). Combination of PDT and BEZ 235 (BEZ), a pan-PI3/ mTOR kinase inhibitor additively enhanced efficacy of sub-lethal PDT in both cell lines. The combination of the pan-PI3/ mTOR kinase inhibitor LY294002 (LY) with PDT also enhanced efficacy of PDT in PC3 in an additive manner but synergistically in SVEC. In order to determine the mechanism of enhancement of efficacy, we assessed apoptosis and autophagy following PDT. PDT-mediated apoptosis was enhanced in endothelial cells, by both BEZ and LY rapidly after treatment. Compared to SVEC, PC3 cells are apoptosis-deficient and apoptosis was not significantly enhanced by either LY or BEZ. However, lethal PDT of PC3 cells induced a delayed autophagic response which may be enhanced by combination, depending on PI3K inhibitor and dose.

  5. Structures of Open (R) and Close (T) States of Prephenate Dehydratase (PDT) - Implication of Allosteric Regulation by L-Phenylalanine

    PubMed Central

    Tan, Kemin; Li, Hui; Zhang, Rongguang; Gu, Minyi; Clancy, Shonda T.; Joachimiak, Andrzej

    2011-01-01

    The enzyme prephenate dehydratase (PDT) converts prephenate to phenylpyruvate in L-phenylalanine biosynthesis. PDT is allosterically regulated by L-Phe and other amino acids. We report the first crystal structures of PDT from Staphylococcus aureus in a relaxed (R) state and PDT from Chlorobium tepidum in a tense (T) state. The two enzymes show low sequence identity (27.3%) but the same prototypic architecture and domain organization. Both enzymes are tetramers (dimer of dimers) in crystal and solution while a PDT dimer can be regarded as a basic catalytic unit. The N-terminal PDT domain consists of two similar subdomains with a cleft in between, which hosts the highly conserved active site. In one PDT dimer two clefts are aligned to form an extended active site across the dimer interface. Similarly at the interface two ACT regulatory domains create two highly conserved pockets. Upon binding of the L-Phe inside the pockets, PDT transits from an open to a closed conformation. PMID:18171624

  6. Dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI) of photodynamic therapy (PDT) outcome and associated changes in the blood-brain barrier following Pc 4-PDT of glioma in an athymic nude rat model

    NASA Astrophysics Data System (ADS)

    Belle, Vaijayantee; Anka, Ali; Cross, Nathan; Thompson, Paul; Mott, Eric; Sharma, Rahul; Gray, Kayla; Zhang, Ruozhen; Xu, Yueshuo; Sun, Jiayang; Flask, Chris A.; Oleinick, Nancy L.; Dean, David

    2012-02-01

    Introduction: Dynamic Contrast-Enhanced-Magnetic Resonance Imaging (DCE-MRI) appears to provide an unambiguous means of tracking the outcome of photodynamic therapy (PDT) of brain tumors with the photosensitizer Pc 4. The increase in Gd enhancement observed after Pc 4-PDT may be due to a temporary opening of the blood-brain-barrier which, as noted by others, may offer a therapeutic window. Methods: We injected 2.5 x 105 U87 cells into the brains of 9 athymic nude rats. After 8-9 days peri-tumor DCE-MRI images were acquired on a 7.0 T microMRI scanner before and after the administration of 150 μL Gd. DCE-MRI scans were repeated three times following Pc 4-PDT. Results: The average, normalized peak enhancement in the tumor region, approximately 30-90 seconds after Gd administration, was 1.31 times greater than baseline (0.03 Standard Error [SE]) prior to PDT and was 1.44 (0.02 SE) times baseline in the first Post-PDT scans (Day 11), a statistically significant (p ~ 0.014, N=8) increase over the Pre- PDT scans, and was 1.38 (0.02 SE) times baseline in the second scans (Day 12), also a statistically significant (p ~ 0.008, N=7) increase. Observations were mixed in the third Post-PDT scans (Day 13), averaging 1.29 (0.03 SE) times baseline (p ~ 0.66, N=7). Overall a downward trend in enhancement was observed from the first to the third Post-PDT scans. Discussion: DCE-MRI may provide an unambiguous indication of brain tumor PDT outcome. The initial increase in DCE-MRI signal may correlate with a temporary, PDT-induced opening of the blood-brain-barrier, creating a potential therapeutic window.

  7. Design Concepts for Muon-Based Accelerators

    SciTech Connect

    Ryne, R. D.; Berg, J. S.; Kirk, H. G.; Palmer, R. B.; Stratkis, D.; Alexahin, Y.; Bross, A.; Gollwitzer, K.; Mokhov, N. V.; Neuffer, D.; Palmer, M. A.; Yonehara, K.; Snopok, P.; Bogacz, A.; Roberts, T. J.; Delahaye, J. -P.

    2015-05-01

    Muon-based accelerators have the potential to enable facilities at both the Intensity and the Energy Frontiers. Muon storage rings can serve as high precision neutrino sources, and a muon collider is an ideal technology for a TeV or multi-TeV collider. Progress in muon accelerator designs has advanced steadily in recent years. In regard to 6D muon cooling, detailed and realistic designs now exist that provide more than 5 order-of-magnitude emittance reduction. Furthermore, detector performance studies indicate that with suitable pixelation and timing resolution, backgrounds in the collider detectors can be significantly reduced, thus enabling high-quality physics results. Thanks to these and other advances in design & simulation of muon systems, technology development, and systems demonstrations, muon storage-ring-based neutrino sources and a muon collider appear more feasible than ever before. A muon collider is now arguably among the most compelling approaches to a multi-TeV lepton collider. This paper summarizes the current status of design concepts for muon-based accelerators for neutrino factories and a muon collider.

  8. Neutrino Factory and Muon Collider Fellow

    SciTech Connect

    Hanson, Gail G.; Snopak, Pavel; Bao, Yu

    2015-03-20

    Muons are fundamental particles like electrons but much more massive. Muon accelerators can provide physics opportunities similar to those of electron accelerators, but because of the larger mass muons lose less energy to radiation, allowing more compact facilities with lower operating costs. The way muon beams are produced makes them too large to fit into the vacuum chamber of a cost-effective accelerator, and the short muon lifetime means that the beams must be reduced in size rather quickly, without losing too many of the muons. This reduction in size is called "cooling." Ionization cooling is a new technique that can accomplish such cooling. Intense muon beams can then be accelerated and injected into a storage ring, where they can be used to produce neutrino beams through their decays or collided with muons of the opposite charge to produce a muon collider, similar to an electron-positron collider. We report on the research carried out at the University of California, Riverside, towards producing such muon accelerators, as part of the Muon Accelerator Program based at Fermilab. Since this research was carried out in a university environment, we were able to involve both undergraduate and graduate students.

  9. Muon g-2 Experiment Shimming

    ScienceCinema

    Kiburg, Brendan

    2016-06-28

    The Muon g-2 experiment at Fermilab will use as its primary instrument a 52-foot-wide electromagnet that creates a precise magnetic field. In this video, Fermilab's Brendan Kiburg explains the lengthy process of finely "shimming" that magnetic field into shape.

  10. Cosmic muons, as messengers from the Universe

    NASA Astrophysics Data System (ADS)

    Brancus, I. M.; Rebel, H.

    2015-02-01

    Penetrating from the outer space into the Earth atmosphere, primary cosmic rays are producing secondary radiation by the collisions with the air target subsequently decaying in hadrons, pions, muons, electrons and photons, phenomenon called Extensive air Shower (EAS). The muons, considered as the "penetrating" component, survive the propagation to the Earth and even they are no direct messenger of the Universe, they reflect the features of the primary particles. The talk gives a description of the development of the extensive air showers generating the secondary particles, especially the muon component. Results of the muon flux and of the muon charge ratio, (the ratio between the positive and the negative muons), obtained in different laboratories and in WILLI experiment, are shown. At the end, the contribution of the muons measured in EAS to the investigation of the nature of the primary cosmic rays is emphasized in KASCADE and WILLI-EAS experiments.