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

Interstitial photodynamic therapy (IPDT) using Photofrin II (PII) as photosensitizer has been studied in the rat rhabdomyosarcoma R-1, growing on the thigh or flank of WAG-Rij rats. A light dose-response relationship has been established, for 10 mg PII/kg i.v. and irradiation 24 hr later, with local tumor control as the end point for single IPDT treatments using four cylindrical diffusors simultaneously. A light energy fluence of 150-200 Joule/cm2 (wavelength 625 nm), measured in vivo at the tumor periphery, was required for tumor control. Comparison of tumor response at 5 and 2.5 mg PII/kg with the complete dose response relationship at 10 mg PII/kg suggests drug-light dose reciprocity and indicates that in our tumor model treatment failures are not likely to be caused by variations in (tumor) tissue photosensitizer level, but rather by insufficient light dose or inadequate light dose distribution. Increasing the interval between PII administration and irradiation from 24 hr to 48 hr had no great effect on tumor response to IPDT in this study. Inspection of the original tumor site 100 days after tumor control revealed obvious loss of thigh muscle tissue. Also, recurrent tumors showed a reduced growth rate. Therefore, the relationship between tumor (re)growth and PDT-induced normal tissue damage was studied and the existence of a tumor bed effect was confirmed. The present study indicates that tumor control after a single IPDT treatment is feasible, but that PDT induced damage to a margin of the adjacent normal tissue is probably required.
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PMID:Tumor and normal tissue response to interstitial photodynamic therapy of the rat R-1 rhabdomyosarcoma. 153 69

Both the scope and the levels of activity in basic research and in the clinical applications of PDT, have grown enormously during the past few years. Several studies have examined the synergism of hyperthermia and chemotherapeutic agents in combination with PDT to enhance tumor eradication. The present study investigates the synergism of glucose administration combined with phototherapy. The results of this study suggest that glucose administration is simple and well tolerated, and combined with PDT produces a larger percentage of animals cured than using PDT alone. Furthermore, the results indicate that this approach requires lower amounts of light and might enable dosage reduction of photosensitizer for optimal response, with minimal side effects, to the treatment of cancer.
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PMID:Glucose administration combined with photodynamic therapy of cancer improves therapeutic efficacy. 157 65

Recently published results of tumor response to various photoradiation protocols in photodynamic therapy appear to contradict accepted definitions of photodynamic dose. In this report, the failure of standard dosimetry models to predict therapeutic outcome is interpreted on the basis of PDT-induced oxygen consumption in tumors with relatively low capillary densities. Calculated estimates of oxygen consumption in photodynamic therapy are combined with the Krogh cylinder model of oxygen diffusion. It is shown that, for tissue volumes in which the intercapillary spacing is less than a specific critical distance, oxygen may be considered constant and unaffected by the therapy. Under these conditions, the 1O2 delivered to a given volume of tissue is spatially uniform and proportional to the number of photons absorbed by the sensitizer. When the intercapillary spacing exceeds the critical distance, the dose of 1O2 varies with radial distance from the capillary wall. In this situation, dose may no longer be considered simply in terms of the product of the photon fluence and the sensitizer absorption coefficient. Since fractionation will increase the 1O2 dose only to cells relatively remote from the capillary wall, the analysis further suggests that fractionating the radiation dose should result in an improved therapeutic ratio for photodynamic therapy.
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PMID:Dosimetry in photodynamic therapy: oxygen and the critical importance of capillary density. 159 66

Photodynamic therapy selectively destroys malignant tumors by laser activation of injected hematoporphyrin derivative. Between July 1985 and January 1989, ten patients underwent 13 courses of PDT for relief of endobronchial tumor obstruction due to endstage primary non-small lung cancer. Initial biopsy specimens demonstrated squamous carcinoma in eight patients and adenocarcinoma in two. At the time of treatment, all patients were considered surgically unresectable: T4N2M1(one), T4N2M0(one), T3N3M1(two), T3N2M0(five), and T2N1M0(one). This latter patient had exclusionary medical conditions. The average Karnofsky status was 75 (worst was 60, best was 90). Obstruction was mainstem for six, bronchus intermedius in one, and left upper lobe in three. The average obstruction was 86 +/- 2 percent. Following treatment, the average obstruction was 57 +/- 3 percent. Responses were greater than 50 percent reduction in four and less than 50 percent in six. Half of the patients still had more than 70 percent obstruction following PDT. However, all patients had a decrease in symptoms, especially coughing. Six of ten patients subsequently received external beam radiation. Three of these patients developed significant problems during and following radiation. Side effects of HPD were minimal and included burns in two and mild anasarca in one patient. PDT appears to offer palliation of obstructive symptoms in patients with late stage lung cancer. Since life span is so short in these individuals, physicians must weigh carefully the potential side effects of combination therapy.
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PMID:Photodynamic therapy in the palliation of late stage obstructing non-small cell lung cancer. 169 75

The efficacy of photodynamic therapy tumor destruction is dependent upon both the interruption of the tumor vasculature and the resultant production of unstable oxygen species causing cellular oxidation and death. Chloroaluminum sulfonated phthalocyanine (CASP) is a recently developed photosensitizer. In order to study the direct vascular effects of CASP on a non-tumor system, a rat window chamber was utilized. Twelve rats were implanted with the window chamber, and were divided into two groups of six. Three rats served as controls for each group (receiving light alone, CASP alone, or no treatment). The remaining 6 rats received 10 mg/kg CASP intravenously 4 days after chamber placement. Photoactivation with light was performed 24 hours after injection (power density 200 mW/cm2, irradiance 100 J/cm2, lambda = 675 nm). Utilizing integrating sphere measurements and image analysis, marked vascular changes in the form of initial vasospasm followed by vaso-constriction and loss of chamber neovascularization were noted in the CASP-PDT group. The control groups exhibited no significant changes. Manipulation of the chamber vasculature at strategic time-points may translate into improved response rates for photodynamic therapy in a tumor model.
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PMID:Photodynamic therapy with chloroaluminum sulfonated phthalocyanine in the rat window chamber. 169 40

Between December 1983 and August 1990 25 patients (a total of 29 carcinomas) with roentgenographically occult lung cancer were treated by PDT at National Kinki Central Hospital for Chest Diseases. A complete remission (CR) occurred in 21 carcinomas (72%). Of 19 carcinomas with tumor length of 1 cm or less, 17 ones (89.5%) achieved a CR. Of 21 carcinomas with visible tumor of the peripheral area, 17 ones (85.7%) achieved a CR. Five carcinomas relapsed from 7 to 18 months after PDT. The length of tumor and the visibility of peripheral area of tumor are important factors for CR and relapse. Fourteen patients (56%) had double, triple or quadruple cancers. Until now, 10 patients died. The main causes of death were metachronous secondary cancers and respiratory or heart failure. PDT have a potential to become an alternative to surgical resection as the primary treatment for early stage roentgenographically occult lung cancer.
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PMID:[Photodynamic therapy of roentgenographically occult lung cancer]. 173 47

Dunning R3327-AT prostate carcinomas growing in Fischer X Copenhagen rats were treated with interstitial photodynamic therapy (PDT--15 mg/kg Photofrin II 4 hours before illumination with 630-nm light via four parallelly implanted optical fibers) at different light intensities. Forty to 60 minutes after treatment, 31P-nuclear magnetic resonance spectra of tumors in anesthetized animals were obtained at 2.35 Tesla using surface coil localization. Areas under resonance peaks were normalized to the area under the peak of a phosphorus standard positioned at a fixed distance on the opposite side of the surface coil. Tumor concentrations of phosphomonoesters and phosphodiesters showed no change after tumor light doses up to 3000 J. Phosphocreatine, alpha-adenosine triphosphate (ATP), beta-ATP, and gamma-ATP signals decreased and inorganic phosphate signals increased with increasing light doses. The intratumor pH did not change significantly at these short times after PDT. In other R3327-AT and R3327-H tumor-bearing animals, [3H]misonidazole was administered 30 minutes prior to PDT treatments of both tumors. Twenty-four hours later, the tumors were resected in toto, and levels of retained [3H]misonidazole were determined in lased tumor specimens by liquid scintillation procedures. The amount of [3H]misonidazole activity in tumor tissue (covalently bound after hypoxic reduction) increased with light doses up to 3000 J. Sensitizer-adduct formation was found to correlate with the ratio of the concentration of inorganic phosphate to that of beta-ATP, both of which are presumed measures of tumor oxygenation status. These measurements have high-lighted the heterogenous nature of the oxygenation status of these experimental tumors. The precision of each assay for estimating tumor oxygenation is discussed.
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PMID:Nuclear magnetic resonance spectroscopy and sensitizer-adduct measurements of photodynamic therapy-induced ischemia in solid tumors. 174 18

Numerous photosensitizers with absorption peaks spanning the 600-800 nm "therapeutic window" have been and continue to be synthesized. Structural modifications of the dyes can then be made in order to improve tumor deliverability and retention. Chemical alterations can also enhance the yields of light generated reactive oxygen species. Utilization of lipoproteins, emulsions and antibody conjugates can enhance the selectivity of drug localization. Most cell types and subcellular structures are highly photosensitive and biochemical analysis indicates that cellular target sites associated with PDT correlate with photosensitizer location. In vivo data suggest that vascular and direct tumor cell damage as well as systemic and local immunological reactions are involved in PDT responsiveness. Additional mechanistic, synthetic and developmental studies are required in order to fully appreciate the potentials of PDT. However, continued enthusiasm and support for basic PDT research (as observed during the past 8 years) will depend to a large extent on the outcome of the current clinical trials.
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PMID:Preclinical examination of first and second generation photosensitizers used in photodynamic therapy. 177 31

PDT is a technique in which visible light is used in combination with photosensitizing agents to achieve a tumoricidal effect. Hematoporphyrins are the most commonly used photosensitizers in clinical practice. DHE is the active fraction of hematoporphyrin. Intravenously injected DHE is found in highest concentration in the liver followed by the spleen, kidney, tumor, skin, muscle, brain, and lungs. The strongest absorption bands for DHE are in the blue region of the spectrum, and this helps to account for the skin toxicity associated with PDT. Red light, at the wavelength of 630 nm, is usually used clinically because of its greater tissue penetration. Techniques such as photobleaching and use of photosensitizers that have weak absorption bands at the lower wavelengths may reduce cutaneous toxicity in the future. Other approaches, such as the use of monoclonal antibody-linked photosensitizers or cationic photosensitizers that are specifically localized in tumor cells, may also increase the effectiveness of PDT while decreasing toxicity. Light for PDT is usually provided by argon-pumped dye lasers or metal vapor lasers. Diode lasers will be used in the future. The use of fiber-optics and diffusing lenses allows the endoscopic and interstitial use of PDT. The mechanism of action of PDT involves the formation of singlet oxygen, which oxidizes biologic molecules and causes irreversible subcellular damage. The major in vivo effect of PDT is caused by its destruction of tumor vasculature, causing anoxia and necrosis. The use of PDT in gynecology has been limited. Several investigators have reported mixed results in treating lower genital tract intraepithelial and recurrent malignant tumors using a variety of approaches involving PDT. The use of PDT in other similar, though nongynecologic, tumors offers a direction for future research.
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PMID:Photodynamic therapy in gynecology. 195 68

The effects of pre-treatment with a novel PFC emulsion on PDT-induced tumor necrosis have been studied in mice. Injection of emulsion either 2.5 hr or 24 hr before PDT did not affect the depth of tumour necrosis. However, pre-treatment with the emulsion appeared to protect skin against photodynamic damage although the mechanism(s) and active principle(s) involved were not identified. These results suggest that there may be specific advantages in using emulsified PFCs in conjunction with PDT which may be independent of changes in tumour oxygenation.
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PMID:Perfluorochemicals and photodynamic therapy in mice. 209 33


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