Biomedical subjects
N J Razum
Publications and source records attributed to N J Razum.
Photodynamic therapy for nonmelanoma skin cancer.
Explore the source record for details and available documents.
In vitro and in vivo light dose rate effects related to hematoporphyrin derivative photodynamic therapy.
In vitro and in vivo experiments were performed to evaluate the parameter of light dose rate as it relates to the efficiency of hematoporphyrin derivative (HPD)-induced photosensitization. Exponentially growing Chinese hamster ovary cells were incubated with HPD (25 micrograms/ml) and were then exposed to red light (630 nm) delivered at different dose rates. A total of five dose rates (0.5, 5.0, 15, 23, and 60 milliwatts/sq cm) were examined following a 1-hr HPD incubation, two dose rates (1 and 20 milliwatts/sq cm) were examined after a 12-hr HPD incubation, and three dose rates (0.4, 4, and 40 milliwatts/sq cm) were examined following a 16-hr incubation and a 30-min serum wash protocol. The effect of light dose rate was determined from cell survival curves obtained by standard clonogenic colony formation assays. Similar levels of cellular toxicity were obtained when cells from each HPD incubation group were treated with equal doses of red light delivered at different dose rates. For in vivo experiments, albino mice were given injections of HPD (7.5 mg/kg) and 24 h later the right hind leg of each mouse was treated with localized red light (630 nm). A total dose of 270 J/sq cm was delivered to the right hind leg at dose rates of 5, 25, or 125 milliwatts/sq cm. The resulting acute skin damage induced by HPD photosensitization was scored over a 30-day period, and skin response curves for the three dose rates were obtained. Comparable levels of damage were induced in each of the three experimental groups. The results obtained from both in vitro and in vivo studies indicate that the photosensitizing efficiency of HPD photodynamic therapy is not affected by nonthermal variations in clinically relevant dose rates of delivered light.
Photodynamic therapy of intraocular tumors: examination of hematoporphyrin derivative distribution and long-term damage in rabbit ocular tissue.
Studies were performed to determine the distribution of hematoporphyrin derivative (HPD) in ocular structures and to characterize long-term damage associated with ocular HPD photodynamic therapy. Pigmented rabbits with an amelanotic melanoma heterotransplanted to the iris were used to obtain quantitative tissue levels of HPD as well as to document HPD localization by fluorescence microscopy. HPD was administered i.v., and tissue concentrations of HPD were determined by spectrofluorometry following porphyrin extraction. Vascular structures such as the tumor, iris, and choroid-retina as well as the aqueous fluid from eyes containing tumors demonstrated rapid HPD localization. The sclera had minimal HPD uptake, and the drug was not detected in avascular structures such as the lens or cornea. HPD was cleared from all ocular structures except the tumor and choroid-retina by 24 h following injection. Fluorescence microscopy data indicate that HPD remained in the avascular photoreceptor cell outer segments of the retina. Long-term damage was documented in rabbits which received HPD photodynamic therapy to a 1-sq cm area of retina via transpupillary light delivery. Acute damage to the exposed area of retina (in the form of a chorioretinal scar) could be induced. This damage was permanent but not progressive. Lens opacities were not observed, and the cornea, aqueous, and vitreous remained clear on all test eyes. The results from these studies suggest that HPD photodynamic therapy may provide a selective and safe approach to the treatment of ocular tumors.