Photodynamic therapy in the canine prostate using motexafin lutetium.
(9/446)
Our purpose was to determine the feasibility of comprehensive treatment of the canine prostate with photodynamic therapy (PDT) using motexafin lutetium (Lu-Tex) and to evaluate the toxicity and tissue effects associated with this treatment. Twenty-five adult male beagles with normal prostate glands were given an i.v. injection of the second-generation photosensitizer Lu-Tex (2-6 mg/kg). An additional two dogs were used as controls and did not receive any photosensitizing drug. All 27 dogs underwent laparotomy to expose the prostate. Three hours postinjection, a total dose of 75-150 J/cm of 732 nm laser light was delivered interstitially and/or transurethrally to the prostate via cylindrical diffusing fibers. Dogs were euthanized between 2 days and 3 months after PDT. All subjects were monitored for clinical evidence of toxicity. Specimens were examined macroscopically and microscopically to characterize the tissue reaction and assess extent of tissue effect as a result of treatment. Interstitial and/or transurethral PDT were successfully delivered in all dogs with no perioperative complications. No clinical evidence of acute urinary obstruction or rectal bleeding was noted. At all dose levels, macroscopic and microscopic evaluation revealed a prostatic tissue reaction characterized initially (within 48 h) by inflammation and necrosis followed by fibrosis and glandular epithelial atrophy. Comprehensive treatment of the entire prostate could be achieved using the interstitial alone approach or combined transurethral and interstitial approach. The transurethral alone approach did not result in complete coverage of the prostate. Dogs receiving transurethral or combined interstitial and transurethral treatment developed erythema and urethral epithelial disruption at all dose levels. Those receiving combined treatment at the highest dose level (Lu-Tex 6 mg/kg, 150 J/cm light) developed urethral fistulae and peritonitis. Dogs treated with the interstitial alone approach were found to have the least amount of urethral damage. Comprehensive treatment of the canine prostate with Lu-Tex PDT is feasible using an interstitial alone or combined interstitial and transurethral approach. The interstitial alone technique results in the least amount of toxicity. The prostatic tissue reaction to treatment is characterized by initial inflammation and necrosis followed by fibrosis and glandular epithelial atrophy. (+info)
Epidermal growth factor receptor-targeted immunophotodiagnosis and photoimmunotherapy of oral precancer in vivo.
(10/446)
Immunophotodiagnosis uses a fluorescence-labeled monoclonal antibody (MAb) that recognizes a tumor-associated antigen to image the fluorescence emitted from the fluorophore-bound MAb that has localized in the tissue. It may be used to diagnose malignant or precancerous lesions, to delineate the margins for tumor resection, or as a feedback mechanism to assess response to treatment. In oral precancer, the epidermal growth factor receptor (EGFR) is overexpressed and could be used as a marker for early detection or as a target for therapy. The goal of this study was to test an anti-EGFR MAb (C225) coupled to either the near-infrared fluorescent dye N,N'-di-carboxypentyl-indodicarbocyanine-5,5'-disulfonic acid for detection or a photochemically active dye (chlorin(e6)) for therapy of early premalignancy in the hamster cheek pouch carcinogenesis model. Fluorescence levels in the carcinogen-treated tissue correlated with the histological stage of the lesions when the C225-N,N'-di-carboxypentyl-indodicarbocyanine-5,5'-disulfonic acid conjugate was used but did not do so with the irrelevant conjugates. Discrete areas of clinically normal mucosa with high fluorescence (hot spots) were subsequently shown by histology to contain dysplastic areas. The best contrast between normal and carcinogen-treated cheek pouches was found at 4-8 days after injection. To test the potential of immunophotodiagnosis as a feedback modality for therapeutic intervention, experiments were conducted with the same MAb conjugated to chlorin(e6) followed by illumination to reduce expression of the EGFR by a photodynamic effect. Subsequent immunophotodiagnosis showed that this treatment led to a significant reduction in fluorescence in the carcinogen-treated cheek pouch compared with nonilluminated areas. This difference between illuminated and dark areas was not seen in the normal cheek pouch. Taken together, the results demonstrate the potential for development of immunophotodiagnosis as a diagnostic tool and as a method of monitoring response to therapy and that the EGFR may be an appropriate target in head and neck cancer. (+info)
Oxygen consumption and resting energy expenditure during phototherapy in full term and preterm newborn infants.
(11/446)
OBJECTIVES: To determine the effect of phototherapy on the oxygen consumption and resting energy expenditure of term and preterm newborn infants. METHODS: A total of 202 infants (gestation 30-42 weeks; body weight 1270-4100 g) requiring phototherapy for the treatment of neonatal hyperbilirubinaemia were enrolled in a randomised crossover study. In random sequence, the oxygen consumption and resting energy expenditure were measured twice in each infant by indirect calorimetry, once at the end of six hours of continuous phototherapy and once after a control period of at least six hours without phototherapy. Anterior abdominal wall temperature was servocontrolled at 36.5 degrees C throughout the study. RESULTS: At the end of six hours of continuous phototherapy, oxygen consumption (mean (SD): 6.21 (1.35) v 6.26 (1.51) ml/kg, p = 0.555) and resting energy expenditure (178.11 (37.62) v 180.37 (43.14) kJ/kg/24 h, p = 0.382) did not differ significantly from those measured after the control period. There were also no significant differences in heart rate, respiratory rate, or rectal temperature. Subgroup analysis of those of gestation < 37 weeks or < 34 weeks also showed no effect of phototherapy on either oxygen consumption or resting energy expenditure. CONCLUSION: Phototherapy has no effect on the metabolic rate of thermally stable term or preterm infants. (+info)
Comparison of treatments for congenital nonobstructive nonhaemolytic hyperbilirubinaemia.
(12/446)
A patient with Crigler-Najjar disease has survived with the help of phototherapy to the age of 2 years without neurological damage. Because long periods of phototherapy are a threat to normal development, a search was made for supplementary treatments. Cholestyramine and a high fat diet were effective, and possibly also aspartic acid. Maintenance therapy with cholestyramine allowed the amount of phototherapy given to be reduced. (+info)
Photochemotherapy of glioma cells by visible light and hematoporphyrin.
(13/446)
Malignant tumors take up and retain hematoporphyrin to a much greater extent than do normal tissues. Porphyrins are photodynamic agents that sensitize cells so that they are damaged by exposure to light. Treatment with hematoporphyrin followed by irradiation with light can destroy glioma cells in culture in less than 8 min and gliomas growing s.c. in rats in about 40 min. Photochemotherapy may become useful in the management of malignant tumors that are resistant to current methods of treatment. (+info)
Photoactivation of DNA thiobases as a potential novel therapeutic option.
(14/446)
The thiopurines, 6-thioguanine and 6-mercaptopurine, are antileukemic agents that are incorporated into DNA following retrieval by the purine salvage pathway (see [1] for a review). Their toxicity requires active DNA mismatch repair (MMR), and thiopurine resistance is an acknowledged phenotype of MMR-defective cells [2, 3]. In addition to these direct cytotoxic effects, DNA thiobases have distinctive photochemical properties [4], the therapeutic potential of which has not been extensively evaluated. We report here that the thiopyrimidine nucleoside 4-thiothymidine is incorporated into DNA. It does not induce MMR-related toxicity, but it interacts synergistically with UVA light and dramatically sensitizes cultured human cells to very low, nonlethal UVA doses. 4-thiothymidine induced UVA dose enhancements of around 100-fold in DNA repair-proficient cells. Nucleotide excision repair-defective xeroderma pigmentosum cells were sensitized up to 1000-fold, implicating bulky DNA photoproducts in the lethal effect. The synergistic action of thiothymidine plus UVA required thymidine kinase, indicating a selective toxicity toward rapidly proliferating cells. Cooperative UVA cytotoxicity is a general property of DNA thiobases, and 6-thioguanine and 4-thiodeoxyuridine were also UVA sensitizers. Thiobase/UVA treatment may offer a novel therapeutic approach for the clinical management of nonmalignant conditions like psoriasis or for superficial tumors that are accessible to phototherapy. (+info)
Early response to light therapy partially predicts long-term antidepressant effects in patients with seasonal affective disorder.
(15/446)
OBJECTIVE: To determine if the antidepressant effect of 1 hour of light therapy is predictive of the response after 1 and 2 weeks of treatment in patients with seasonal affective disorder (SAD). PATIENTS: Twelve patients with SAD. SETTING: National Institutes of Health Clinical Center, Bethesda, Md. INTERVENTIONS: Light therapy for 2 weeks. OUTCOME MEASURES: Scores on the Seasonal Affective Disorder Version of the Hamilton Depression Rating Scale (SIGH-SAD) on 4 occasions (before and after 1 hour of light therapy and after 1 and 2 weeks of therapy) in the winter when the patients were depressed. Change on typical and atypical depressive scores at these time points were compared. RESULTS: Improvement of atypical depressive symptoms after 1 hour of light therapy positively correlated with improvement after 2 weeks of therapy. CONCLUSION: In patients with SAD, the early response to light therapy may predict some aspects of long-term response to light therapy, but these results should be treated with caution until replicated. (+info)
The effect of porphyrins on normal and transformed mouse cell lines in the presence of visible light.
(16/446)
Photodynamic therapy consists of the uptake of a photosensitizing dye, often a porphyrin, by tumor tissue and subsequent irradiation of the tumor with visible light of an appropriate wavelength matched to the absorption spectrum of the photosensitizing dye. This class of molecules produces reactive oxygen species when activated by light, resulting in a direct or indirect cytotoxic effect on the target cells. Photodynamic therapy has been used in the treatment of cancer but the technology has a potential for the treatment of several disease conditions mainly because of its selectivity. However, it is not clear why the porphyrins are retained preferentially by abnormal tissue. This paper describes a study of the effect of the association of porphyrin and visible light on two mouse fibroblast cell lines: A31, normal cells and B61, an EJ-ras transformed variant of A31. Two water-soluble porphyrins were used, a positively charged one, tetra(N-methyl-4-pyridyl)porphyrin chloride, and a negatively charged one, tetra(4-sulfonatophenyl)porphyrin-Na salt (TPPS4) in order to assess the effect on cell survival. The results suggest that the B61 cell line is more sensitive to incubation with the anionic porphyrin (TPPS4) followed by light irradiation and that the anionic porphyrin is more efficient in killing the cells than the cationic porphyrin. (+info)