54 research outputs found
Recommended from our members
Cell Death Pathways in Photodynamic Therapy of Cancer
Photodynamic therapy (PDT) is an emerging cancer therapy that uses the combination of non-toxic dyes or photosensitizers (PS) and harmless visible light to produce reactive oxygen species and destroy tumors. The PS can be localized in various organelles such as mitochondria, lysosomes, endoplasmic reticulum, Golgi apparatus and plasma membranes and this sub-cellular location governs much of the signaling that occurs after PDT. There is an acute stress response that leads to changes in calcium and lipid metabolism and causes the production of cytokines and stress response mediators. Enzymes (particularly protein kinases) are activated and transcription factors are expressed. Many of the cellular responses center on mitochondria and frequently lead to induction of apoptosis by the mitochondrial pathway involving caspase activation and release of cytochrome c. Certain specific proteins (such as Bcl-2) are damaged by PDT-induced oxidation thereby increasing apoptosis, and a build-up of oxidized proteins leads to an ER-stress response that may be increased by proteasome inhibition. Autophagy plays a role in either inhibiting or enhancing cell death after PDT
Cell Death Pathways in Photodynamic Therapy of Cancer
Photodynamic therapy (PDT) is an emerging cancer therapy that uses the combination of non-toxic dyes or photosensitizers (PS) and harmless visible light to produce reactive oxygen species and destroy tumors. The PS can be localized in various organelles such as mitochondria, lysosomes, endoplasmic reticulum, Golgi apparatus and plasma membranes and this sub-cellular location governs much of the signaling that occurs after PDT. There is an acute stress response that leads to changes in calcium and lipid metabolism and causes the production of cytokines and stress response mediators. Enzymes (particularly protein kinases) are activated and transcription factors are expressed. Many of the cellular responses center on mitochondria and frequently lead to induction of apoptosis by the mitochondrial pathway involving caspase activation and release of cytochrome c. Certain specific proteins (such as Bcl-2) are damaged by PDT-induced oxidation thereby increasing apoptosis, and a build-up of oxidized proteins leads to an ER-stress response that may be increased by proteasome inhibition. Autophagy plays a role in either inhibiting or enhancing cell death after PDT.National Institutes of Health (U.S.) (NIH grant R01AI050875)Center for Integration of Medicine and Innovative Technology (DAMD17-02-2-0006)United States. Dept. of Defense. Congressionally Directed Medical Research Programs (CDMRP Program in TBI (W81XWH-09-1-0514))United States. Air Force Office of Scientific Research (FA9950-04-1-0079)National Institutes of Health (U.S.) (NIH Dermatology training grant
Cellular and Vascular effects of the photodynamic agent temocene are modulated by the delivery vehicle
The effects of the drug delivery system on the PDT activity, localization, and tumor accumulation of the novel photosensitizer temocene (the porphycene analogue of temoporfin or m-tetrahydroxyphenyl chlorin) were investigated against the P815 tumor, both in vitro and in DBA/2 tumor bearing mice. Temocene was administered either free (dissolved in PEG400/EtOH mixture), or encapsulated in Cremophor EL micelles or in DPPC/ DMPG liposomes, chosen as model delivery vehicles. The maximum cell accumulation and photodynamic activity in vitro was achieved with the free photosensitizer, while temocene in Cremophor micelles hardly entered the cells. Notwithstanding, the micellar formulation showed the best in vivo response when used in a vascular regimen (short drug light interval), whereas liposomes were found to be an efficient drug delivery system for a tumor cell targeting strategy (long drug-light interval). PEG/EtOH formulation was discarded for further in vivo experiments as it provoked lethal toxic effects caused by photosensitizer aggregation. These results demonstrate that drug delivery systems modulate the vascular and cellular outcomes of photodynamic treatments with temocene. Β© 2012 Elsevier B.V. All rights reserved
Microlensing optical depth and event rate in the OGLE-IV Galactic plane fields
Searches for gravitational microlensing events are traditionally concentrated
on the central regions of the Galactic bulge but many microlensing events are
expected to occur in the Galactic plane, far from the Galactic Center. Owing to
the difficulty in conducting high-cadence observations of the Galactic plane
over its vast area, which are necessary for the detection of microlensing
events, their global properties were hitherto unknown. Here, we present results
of the first comprehensive search for microlensing events in the Galactic
plane. We searched an area of almost 3000 square degrees along the Galactic
plane (|b|<7, 0<l<50, 190<l<360 deg) observed by the Optical Gravitational
Lensing Experiment (OGLE) during 2013-2019 and detected 630 events. We
demonstrate that the mean Einstein timescales of Galactic plane microlensing
events are on average three times longer than those of Galactic bulge events,
with little dependence on the Galactic longitude. We also measure the
microlensing optical depth and event rate as a function of Galactic longitude
and demonstrate that they exponentially decrease with the angular distance from
the Galactic Center (with the characteristic angular scale length of 32 deg).
The average optical depth decreases from at l=10 deg to
in the Galactic anticenter. We also find that the optical
depth in the longitude range 240<l<330 deg is asymmetric about the Galactic
equator, which we interpret as a signature of the Galactic warp.Comment: ApJS, in pres
The Araucaria Project: A study of the classical Cepheid in the eclipsing binary system OGLE LMC562.05.9009 in the Large Magellanic Cloud
We present a detailed study of the classical Cepheid in the double-lined,
highly eccentric eclipsing binary system OGLE-LMC562.05.9009. The Cepheid is a
fundamental mode pulsator with a period of 2.988 days. The orbital period of
the system is 1550 days. Using spectroscopic data from three 4-8-m telescopes
and photometry spanning 22 years, we were able to derive the dynamical masses
and radii of both stars with exquisite accuracy. Both stars in the system are
very similar in mass, radius and color, but the companion is a stable,
non-pulsating star. The Cepheid is slightly more massive and bigger (M_1 = 3.70
+/- 0.03M_sun, R_1 = 28.6 +/- 0.2R_sun) than its companion (M_2 = 3.60 +/-
0.03M_sun, R_2 = 26.6 +/- 0.2R_sun). Within the observational uncertainties
both stars have the same effective temperature of 6030 +/- 150K. Evolutionary
tracks place both stars inside the classical Cepheid instability strip, but it
is likely that future improved temperature estimates will move the stable giant
companion just beyond the red edge of the instability strip. Within current
observational and theoretical uncertainties, both stars fit on a 205 Myr
isochrone arguing for their common age. From our model, we determine a value of
the projection factor of p = 1.37 +/- 0.07 for the Cepheid in the
OGLE-LMC562.05.9009 system. This is the second Cepheid for which we could
measure its p-factor with high precision directly from the analysis of an
eclipsing binary system, which represents an important contribution towards a
better calibration of Baade-Wesselink methods of distance determination for
Cepheids.Comment: Accepted to be published in Ap
OGLE-2018-BLG-0532Lb: Cold Neptune With Possible Jovian Sibling
We report the discovery of the planet OGLE-2018-BLG-0532Lb, with very obvious
signatures in the light curve that lead to an estimate of the planet-host mass
ratio . Although there are
no obvious systematic residuals to this double-lens/single-source (2L1S) fit,
we find that can be significantly improved by adding either a third
lens (3L1S, ) or second source (2L2S, ) to
the lens-source geometry. After thorough investigation, we conclude that we
cannot decisively distinguish between these two scenarios and therefore focus
on the robustly-detected planet. However, given the possible presence of a
second planet, we investigate to what degree and with what probability such
additional planets may affect seemingly single-planet light curves. Our best
estimates for the properties of the lens star and the secure planet are: a host
mass , system distance kpc and planet mass
with projected separation au.
However, there is a relatively bright (and also relatively blue) star
projected within mas of the lens, and if future high-resolution images
show that this is coincident with the lens, then it is possible that it is the
lens, in which case, the lens would be both more massive and more distant than
the best-estimated values above.Comment: 48 pages, 9 figures, 7 table
Photodynamic Therapy Can Induce a Protective Innate Immune Response against Murine Bacterial Arthritis via Neutrophil Accumulation
Background:
Local microbial infections induced by multiple-drug-resistant bacteria in the orthopedic field can be intractable, therefore development of new therapeutic modalities is needed. Photodynamic therapy (PDT) is a promising alternative modality to antibiotics for intractable microbial infections, and we recently reported that PDT has the potential to accumulate neutrophils into the infected site which leads to resolution of the infection. PDT for cancer has long been known to be able to stimulate the innate and adaptive arms of the immune system.
Methodology/Principal Findings:
In the present study, a murine methicillin-resistant Staphylococcus aureus (MRSA) arthritis model using bioluminescent MRSA and polystyrene microparticles was established, and both the therapeutic (Th-PDT) and preventive (Pre-PDT) effects of PDT using methylene blue as photosensitizer were examined. Although Th-PDT could not demonstrate direct bacterial killing, neutrophils were accumulated into the infectious joint space after PDT and MRSA arthritis was reduced. With the preconditioning Pre-PDT regimen, neutrophils were quickly accumulated into the joint immediately after bacterial inoculation and bacterial growth was suppressed and the establishment of infection was inhibited.
Conclusions/Significance:
This is the first demonstration of a protective innate immune response against a bacterial pathogen produced by PDT.National Institutes of Health (U.S.) (Grant number R01AI050875
Photodynamic Therapy of Tumors Can Lead to Development of Systemic Antigen-Specific Immune Response
Background:
The mechanism by which the immune system can effectively recognize and destroy tumors is dependent on recognition of tumor antigens. The molecular identity of a number of these antigens has recently been identified and several immunotherapies have explored them as targets. Photodynamic therapy (PDT) is an anti-cancer modality that uses a non-toxic photosensitizer and visible light to produce cytotoxic reactive oxygen species that destroy tumors. PDT has been shown to lead to local destruction of tumors as well as to induction of anti-tumor immune response.
Methodology/Principal Findings:
We used a pair of equally lethal BALB/c colon adenocarcinomas, CT26 wild-type (CT26WT) and CT26.CL25 that expressed a tumor antigen, Ξ²-galactosidase (Ξ²-gal), and we treated them with vascular PDT. All mice bearing antigen-positive, but not antigen-negative tumors were cured and resistant to rechallenge. T lymphocytes isolated from cured mice were able to specifically lyse antigen positive cells and recognize the epitope derived from beta-galactosidase antigen. PDT was capable of destroying distant, untreated, established, antigen-expressing tumors in 70% of the mice. The remaining 30% escaped destruction due to loss of expression of tumor antigen. The PDT anti-tumor effects were completely abrogated in the absence of the adaptive immune response.
Conclusion:
Understanding the role of antigen-expression in PDT immune response may allow application of PDT in metastatic as well as localized disease. To the best of our knowledge, this is the first time that PDT has been shown to lead to systemic, antigen- specific anti-tumor immunity.United States. National Cancer Institute (grant RO1CA/AI838801)United States. National Cancer Institute (grant R01AI050875
- β¦