aluminum-phthalocyanine-disulfonate and temoporfin

Photodynamic therapy is an attractive technique for various skin tumors and non-cancerous skin lesions. However, while the aim of photodynamic therapy is to target and damage only the malignant cells, it unavoidably affects some of the healthy cells surrounding the tumor as well. However, data on the effects of PDT to normal cells are scarce, and the characterization of the pathways activated after the photodamage of normal cells may help to improve clinical photodynamic therapy. In our study, primary human epidermal keratinocytes were used to evaluate photodynamic treatment effects of photosensitizers with different subcellular localization. We compared the response of keratinocytes to lysosomal photodamage induced by phthalocyanines, aluminum phthalocyanine disulfonate (AlPcS

Topics: Apoptosis; Autophagy; Cell Differentiation; Computer Simulation; Humans; Indoles; Isoindoles; Keratinocytes; Kinetics; Lysosomes; Mesoporphyrins; Models, Biological; Organometallic Compounds; Photochemotherapy; Photosensitizing Agents

Recent studies have demonstrated an effect of photodamage on the endocytic pathway involved in recycling of membrane components. Using a series of agents with known sub-cellular targets, we explored the determinants of photodynamic inhibition of endocytic processes in three cell lines: A murine leukemia, a murine hepatoma, and a non-malignant epithelial cell line of human origin.. The PI-3 kinase antagonist wortmannin blocks endosomal processing pathway dependent on this enzyme, providing an indication of the "flux" of endocytosis. Microscopic observations were used to assess the effect of photodamage on this pathway. Photosensitizing agents specific for mitochondrial, endoplasmic reticulum (ER), lysosomal, and endosomal photodamage were employed.. Sub-lethal photodamage directed against endosomes or lysosomes interrupted early steps in this endocytic process in the hepatoma cell line. A mechanism for these effects is proposed. Mitochondrial photodamage could interrupt endocytosis, but at levels that also induced apoptosis. ER photodamage did not affect endocytosis even at lethal levels. Somewhat similar results were obtained with other cell lines, but there were sufficient differences to indicate that the cell phenotype is, in part, a determinant of the endocytic response to PDT.. PDT is therefore seen to have an effect on endocytic processes. Further work will be needed to delineate the role of these endocytic effects in the array of responses to photodynamic therapy.

Topics: Androstadienes; Animals; Carcinoma, Hepatocellular; Cell Line; Cell Line, Tumor; Endocytosis; Epithelial Cells; Humans; Indoles; Leukemia; Liver Neoplasms; Mesoporphyrins; Mice; Models, Biological; Organelles; Organometallic Compounds; Phosphodiesterase Inhibitors; Photochemotherapy; Photosensitizing Agents; Porphyrins; Wortmannin

Further to our work on the feasibility of application of photodynamic therapy (PDT) to the canine prostate, this study evaluates the biological responses of the prostate and adjacent vital structures with meso-tetra-(m-hydroxylphenyl) chlorin (mTHPC) or aluminum disulfonated phthalocyanine (AlS2Pc) based PDT as a preparatory step for clinical trials. Skin photosensitivity was not particularly problematic if light protection could be implemented properly for 2 weeks following sensitization. Prostate PDT was well tolerated by the experimental animals with only minor physical distress. mTHPC was more powerful than AlS2Pc in terms of prostate lesions induced. A large portion of prostate tissue could be destroyed by PDT with 4 punctures. Physical distress was probably caused by severe urethral irritation and aching from acute swelling of the prostate. Although the voiding condition normalized within 10 days, regeneration of urethral epithelium was not complete until 3-4 weeks after PDT. Improper placement of laser fiber caused extensive ecchymosis of the retroperitoneal organs. The biological significance of PDT induced hyperemia in the periprostatic structures remains poorly defined. Neither periprostatic nerve damage nor rectal lesions were seen in dogs receiving either mTHPC or AlS2Pc. Glandular atrophy with papillary cystic regeneration of the prostate was the most prominent finding 90 days after PDT. The glandular architecture was well preserved because the interlobular collagens were less affected than the cellular components of the glands. Our study suggests that PDT with mTHPC and AlS2Pc is safe and promising for necrosing a substantial amount of prostate tissue. The completeness of treatment and long-term therapeutic effectiveness for prostate cancer, however, remains to be determined through further investigation.

Topics: Animals; Dogs; Epithelium; Indoles; Male; Mesoporphyrins; Organometallic Compounds; Photochemotherapy; Photosensitizing Agents; Prostate; Prostatic Neoplasms; Rectal Diseases; Skin; Urethral Diseases; Urination Disorders