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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The tumoricidal effect of Foscan-mediated photodynamic therapy may involve both vessel and tumor cell destruction. The relevant importance of each mechanism seems to be defined by the time interval between photosensitizer administration and illumination (drug-light interval, DLI). Short drug-light intervals favor vascular damage due to the preferential photosensitizer accumulation in the tumor vasculature, whereas long drug-light intervals trigger direct tumor cell damage due to the dye localization in the tumor. The purpose of this study was to investigate the influence of tumor, plasma and leukocyte concentrations of Foscan at different times after photosensitizer delivery on PDT response. Both pharmacokinetic and tumor-response studies were carried out in nude mice bearing s.c. Colo26 tumors. One to 96 h after i.v. injection of 0.5 mg/kg Foscan, animals were exposed to 10 J/cm(2) 652-nm light delivered at 30 mW/cm(2). Mean tumor regrowth time was determined for each schedule of treatment and correlated to Foscan distribution in the compartments of interest at the time of illumination. PDT efficacy was greatest for irradiations performed at 6 and 12 h post Foscan injection and limited at 96 h. Unlike tumor and plasma Foscan concentrations, photosensitizer accumulation in leukocytes exhibited a good correlation with PDT efficacy. The results suggest that leukocytes could play an important role in the mechanism of PDT-induced vascular damage either by being one of the main effector compartments or by better reflecting Foscan accumulation in endothelial cells compared to plasma. The prevalence of indirect damage was highlighted by the fact that PDT efficacy was not modified by the use of a higher fluence rate of irradiation (160 mW/cm(2)), which depleted intratumor oxygen and did not restrain PDT-induced cell toxicity.
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PMID:Foscan-based photodynamic treatment in vivo: correlation between efficacy and Foscan accumulation in tumor, plasma and leukocytes. 1528 49

Hypocrellin B (HB), a monomeric perylenequinone pigment, is a promising second-generation photosensitizer for photodynamic therapy. We have evaluated the efficacy of HB mediated PDT by experimenting with various drug-light intervals, based on the biodistribution analysis in human bladder tumor (MGH cell line) models. Tumor growth rates were assessed at 10-day post treatment followed by morphometric analysis. Biodistribution of HB was evaluated using spectrofluorophotometry analysis (Ex: 480 nm, Em: 620-630 nm). The level of HB peaked at 6 h postinjection in tumor, peritumoral skin and normal muscle followed by a decline over the next 42 h. Concurrently, the ratio of drug in tumor versus skin was relatively low at all times in comparison to tumor to muscle ratio. In serum, concentration of HB peaked at 1 h. Almost 88% of its original uptake level was cleared at 48 h. The level of PDT response revealed a strong dependence on the drug-light intervals (DLI) and light dose. For both high and low fluence/fluence rate, comparable tumor response was observed at 1 h DLI; treated tumors exhibited significant tumor regression compared to 6 and 24 h DLI. The absence of tumor response was observed at 24 h DLI even at high light dose (100 J/cm(2); 100 mW/cm(2)). Tumor response detected at low light dose (12 J/cm(2); 12 mW/cm(2)) at short DLI suggests that the tumor vasculature is a more sensitive target compared to the cellular compartment of the tumor, correlating significantly with the bioavailability of the drug in serum. Therefore, HB mediated PDT effect is characteristics of a predominantly vascular mediated effect. This study confirms that for short drug-light intervals, PDT seems to target tumor vasculature, which contributes to tumor destruction.
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PMID:Evaluation of Hypocrellin B in a human bladder tumor model in experimental photodynamic therapy: biodistribution, light dose and drug-light interval effects. 1528 63

Photodynamic therapy is an approved treatment for several types of tumors and certain benign diseases, based on the use of a light-absorbing compound (photosensitizer) and light irradiation. In the presence of molecular oxygen, light-activation of the photosensitizer, which accumulates in cancer tissues, leads to the local production of reactive oxygen species that kill the tumor cells. Mitochondria are central coordinators of the mechanisms by which PDT induces apoptosis in the target cells. Recent studies indicate that concomitant to the permeabilization of the outer mitochondrial membrane (which leads to the release of several apoptogenic factors in the cytosol and to the activation of effector caspases), regulatory signaling pathways are activated in a photosensitizer, PDT dose and cell-dependent fashion. Signaling pathways regulated by members of mitogen activated protein kinases and their downstream targets, such as cyclooxygenase-2, appear to critically modulate cancer cell sensitivity to PDT. Understanding the molecular events that contribute to PDT-induced apoptosis, and how cancer cells can evade apoptotic death, should enable a more rationale approach to drug design and therapy.
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PMID:Regulatory pathways in photodynamic therapy induced apoptosis. 1529 26

The concept of metronomic photodynamic therapy (mPDT) is presented, in which both the photosensitizer and light are delivered continuously at low rates for extended periods of time to increase selective tumor cell kill through apoptosis. The focus of the present preclinical study is on mPDT treatment of malignant brain tumors, in which selectivity tumor cell killing versus damage to normal brain is critical. Previous studies have shown that low-dose PDT using 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) can induce apoptosis in tumor cells without causing necrosis in either tumor or normal brain tissue or apoptosis in the latter. On the basis of the levels of apoptosis achieved and model calculations of brain tumor growth rates, metronomic delivery or multiple PDT treatments, such as hyperfractionation, are likely required to produce enough tumor cell kill to be an effective therapy. In vitro studies confirm that ALA-mPDT induces a higher incidence of apoptotic (terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate, sodium salt nick-end labeling positive) cells as compared with an acute, high-dose regimen (ALA-aPDT). In vivo, mPDT poses two substantial technical challenges: extended delivery of ALA and implantation of devices for extended light delivery while allowing unencumbered movement. In rat models, ALA administration via the drinking water has been accomplished at very high doses (up to 10 times therapeutic dose) for up to 10 days, and ex vivo spectrofluorimetry of tumor (9L gliosarcoma) and normal brain demonstrates a 3-4 fold increase in the tumor-to-brain ratio of PpIX concentration, without evidence of toxicity. After mPDT treatment, histological staining reveals extensive apoptosis within the tumor periphery and surrounding microinvading colonies that is not evident in normal brain or tumor before treatment. Prototype light sources and delivery devices were found to be practical, either using a laser diode or light-emitting diode (LED) coupled to an implanted optical fiber in the rat model or a directly implanted LED using a rabbit model. The combined delivery of both drug and light during an extended period, without compromising survival of the animals, is demonstrated. Preliminary evidence of selective apoptosis of tumor under these conditions is presented.
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PMID:Metronomic photodynamic therapy as a new paradigm for photodynamic therapy: rationale and preclinical evaluation of technical feasibility for treating malignant brain tumors. 1533 4

Photodynamic diagnosis could be a useful tool for improving the diagnostic yield of tumor biopsy, especially for mesothelioma tumors that are sclerotic and particularly hypocellular. For PDD, the use of low doses of a sensitizing drug, such as 5-ALA, must be investigated further. The initial results of 5-ALA-mediated PDD are promising. The role, if any, for PDT in the treatment of mesothelioma has yet to be established. The number of centers exploring this technology is limited because the procedure is labor intensive and requires not only specialized equipment but also physician support. The number of patients treated in the different trials is small, and no definitive conclusions can be drawn. Further complicating the interpretation of published results is the number of variables (i.e., type of sensitizer, light dose, drug dose, drug light interval, methods of light measurement, technique of light delivery, surgical debulking techniques), which differ between studies. Most reports are phase I and II studies. The final outcome of these studies with respect to survival is of limited value. The only phase III study, which was performed with an earlier generation photosensitizer, reported no advantage to the use of PDT in combination with surgery and immunochemotherapy. To date, the most that can be said is that intraoperative PDT can be performed safely in experienced centers and that there are some encouraging results, especially in patients with stages I and II MPM, particularly with the newer generation photosensitizers. One attractive aspect of this adjuvant treatment is that PDT, as opposed to some of the other adjuvant treatments combined with surgery, may offer the option of effecting adequate tumor debulking with a pulmonary-sparing procedure.
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PMID:Innovative therapies: photodynamic therapy. 1555 63

A clinically relevant photosensitizer, 3-devinyl-3-(1-hexyloxyethyl)pyropheophorbide-a (HPPH, a chlorophyll-a derivative), was conjugated with Gd(III)-aminobenzyl-diethylenetriaminepentaacetic acid (DTPA), an experimental magnetic resonance (MR) imaging agent. In vivo reflectance spectroscopy confirmed tumor uptake of HPPH-aminobenzyl-Gd(III)-DTPA conjugate was higher than free HPPH administered intraveneously (iv) to C3H mice with subcutaneously (sc) implanted radiation-induced fibrosarcoma (RIF) tumor cells. In other experiments, Sprague-Dawley (SD) rats with sc implanted Ward Colon Carcinoma cells yielded markedly increased MR signal intensities from tumor regions-of-interest (ROIs) 24 h post-iv injection of HPPH-aminobenzyl-Gd(III)-DTPA conjugate as compared to unconjugated HPPH. In both in vitro (RIF tumor cells) and in vivo (mice bearing RIF tumors and rats bearing Ward Colon tumors) the conjugate produced significant increases in tumor conspicuity at 1.5 T and retained therapeutic efficacy following PDT. Also synthesized were a series of novel bifunctional agents containing two Gd(III) atoms per HPPH molecule that remained tumor-avid and PDT-active and yielded improved MR tumor conspicuity compared to their corresponding mono-Gd(III) analogues. Administered iv at a MR imaging dose of 10 micromol/kg, these conjugates produced severe skin phototoxicity. However, by replacing the hexyl group of the pyropheophorbide-a with a tri(ethylene glycol) monomethyl ether (PEG-methyl ether), these conjugates produced remarkable MR tumor enhancement at 8 h post-iv injection, significant tumoricidal activity (80% of mice were tumor-free on day 90), and reduced skin phototoxicity compared to their corresponding hexyl ether analogues. The poor water-solubility characteristic of these conjugates was resolved by incorporation into a liposomal formulation. This paper presents the synthesis of tumor-avid contrast enhancing agents for MR imaging and thus represents an important milestone toward improving cancer diagnosis and tumor characterization. More importantly, this paper describes a new family of bifunctional agents that combine two modalities into a single cost-effective "see and treat" approach, namely, a single agent that can be used for contrast agent-enhanced MR imaging followed by targeted photodynamic therapy.
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PMID:Chlorophyll-a analogues conjugated with aminobenzyl-DTPA as potential bifunctional agents for magnetic resonance imaging and photodynamic therapy. 1565 73

Our recent study found that a new topical 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) protocol composed of multiple 3-min fractionated irradiations with a light emitting diode (LED) red light at 635 +/- 5 nm for a total of 1000 s (fluence rate: 100 mW/cm(2); light exposure dose: 100 J/cm(2)) after topical application of 20% ALA for 1.5 or 2 h can be used successfully for the treatment of oral verrucous hyperplasia. In this case report, we tested the efficacy of this new treatment protocol of ALA-PDT for an extraoral verrucous carcinoma (VC) lesion at the right mouth angle and an intraoral VC lesion at the right buccal mucosa of a 56-year-old male areca quid chewer and smoker. The extraoral tumor was cleared after six treatments of topical ALA-PDT and the intraoral tumor showed complete regression after 22 treatments of topical ALA-PDT. No recurrence of the VC lesion was found after a follow-up period of 6 months. We suggest that PDT using a topical application of 20% ALA followed by multiple 3-min fractionated irradiations with an LED red light is also an effective and successful treatment modality for VC.
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PMID:Successful treatment of an extensive verrucous carcinoma with topical 5-aminolevulinic acid-mediated photodynamic therapy. 1575 62

In this study, we evaluated the photophysical properties of 5,10,15,20-tetrakis[4-(1,4,7,10,13-pentaoxacyclopentadecane-2-aminomethyl)2,3,5,6-(tetrafluoro)-phenyl]-porphyrin (H2C4P) and Zn(II)5,10,15,20-tetrakis[4-(1,4,7,10,13-pentaoxacyclopenta-decane-2-aminomethyl)2,3,5,6-(tetrafluoro)-phenyl]-porphyrinate (ZnC4P). We observed that these porphyrins have unique properties when compared with classical porphyrins. The porphyrins H2C4P and ZnC4P showed efficient transfer energy S1 to T1 by intersystem crossing with high and reasonable yields of triplet excited state and singlet oxygen production. These amphiphilic structures of these porphyrins could improve its localization in the tumor cells due to the presence of the crown ether in its framework. We also believed that the crown ether could modulate the change in ion homeostase (Ca(+2), K+, Na+) as already described by some new phthalocyanine dye. This fact makes us believe that it could be reasonably used as a photosensitizer for PDT purposes.
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PMID:Photophysical properties of crowned porphyrins. 1585 Apr 25

Most patients with musculoskeletal sarcoma do not recover satisfactory limb function after limb salvage surgery. To achieve satisfactory improvement of limb function, we developed a unique surgical modality of photodynamic therapy using acridine orange (AO-PDT) and clinically applied it to patients with musculoskeletal sarcomas. Ten patients with primary musculoskeletal sarcomas were enrolled in the study. Of these, 6 had primary malignant soft tissue sarcoma and 4 had primary malignant bone tumor. In the AO-PDT procedure, intralesional or partially marginal tumor excision was initially conducted and microscopic curettage of the remnant tumor, which emitted green fluorescence under blue excitation after local administration of 1microg/ml AO solution, was performed using a fluorescence surgical microscope. Subsequently, blue light illuminated there for 10 minutes. The surgical wound was closed, followed by immediate X-ray irradiation of the resected area with 5 Gy in 5 out of 10 patients to enhance the effect of AO-PDT. The follow-up of the patients ranged from 24 to 48 months. All the patients (AO-PDT alone: 5, AO-PDT with 5-Gy radiation: 5) are alive; only one patient showed local recurrence of the tumor. The recurrence rate was 10%. None of the 5 patients treated by AO-PDT with radiation developed local tumor recurrence. The limb function in all the patients, except for one, recovered to the level before surgery. None of the patients clinically showed any local or systemic complications. AO-PDT may be a promising new limb salvage modality for preservation of excellent limb function in patients with musculoskeletal sarcoma.
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PMID:Clinical trial of photodynamic therapy using acridine orange with/without low dose radiation as new limb salvage modality in musculoskeletal sarcomas. 1586 70

We have investigated the role of tissue oxygenation on light penetration into tissue at different wavelengths. As a field of application we have chosen aminolevulinic acid-photodynamic therapy (ALA-PDT). To calculate efficiency spectra of PDT on human skin one needs to know the excitation spectrum of the photosensitizer of interest and the relative fluence rate as a function of depth in the tissue. We measured the former and computed the latter with an accurate radiative transfer algorithm. In this way we determined the efficiency spectra as functions of depth for different types of basal cell carcinomas (BCC). Our results suggest that ALA-PDT works best for nodular BCC at a wavelength of 630 nm, whereas it works best for pigmented superficial BCC at a wavelength of 390 nm. At 630 nm the light penetration into a tumor depends strongly on the oxygenation of the blood. Below a 2 mm thick, well-oxygenated, nodular BCC, we find the efficiency to be an order of magnitude larger than below a poorly oxygenated tumor. At 390 nm, the light penetration into a tumor does not depend on the oxygenation of the blood.
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PMID:Choice of optimal wavelength for PDT: the significance of oxygen depletion. 1593 93


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