Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30536 (PBS)
 9,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hematoporphyrin derivative (HPD) is a photosensitizer for use in photodynamic therapy (PDT). In this paper, HPD was conjugated with monoclonal antibodies 3G9 or 3H11 for use against gastric cancer in order to enhance the photosensitive effect and reduce side effect of PDT. The biological activities of the McAb conjugates were demonstrated. The killing effect on BGC-823 cells of 3G9-HPD or 3H11-HPD conjugates plus exposure to light showed 17 fold and 8.6 fold greater cytotoxicity, respectively than free HPD at an equivalent HPD concentration in vitro. When 3G9-HPD and 3H11-HPD were used in combination at 7:3, 5:5 and 3:7 proportion, the cytotoxicity was increased 12.9, 11.8 and 9.4 fold on target cells, respectively. The results indicate that the cytotoxicity was not further enhanced by the combination scheme. When tumor-bearing nude mice were treated with the different conjugates. Significant inhibition of tumor growth was observed and the survival period of animals was markedly prolonged in comparison with PBS, free HPD and NIgG-HPD treated groups.
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PMID:[Experimental study of anti-tumor effect with conjugates of monoclonal antibodies and hematoporphyrin derivative]. 253 54

Hematoporphyrin derivative (HPD), a sensitizer used in photodynamic therapy (PDT) of malignancies, is progressively destroyed during the treatment. Prior studies suggested that upon PDT the photobleaching of HPD in tumor tissues is largely mediated by self-sensitized singlet oxygen. However, little is known about the role of other reactive oxygen species (ROS). The main aim of this work was to clarify the significance of H2O2, superoxide (O2.(-)) and hydroxyl (OH.) radicals in bleaching of HPD in tumor cells subjected to PDT. Experiments were performed on Ehrlich ascites carcinoma (EAC) cells, which were loaded with HPD in PBS and then irradiated with red light at 630 nm in the same buffer. Studies showed that photosensitization of EAC cells by HPD led to the formation of significant amounts of H2O2, O2.(-) and OH., and that these ROS could be involved in the photobleaching of HPD during PDT. In fact, we found that addition of catalase (CAT, a scavenger H2O2), Cu/Zn-superoxide dismutase (Cu/Zn-SOD) and Tiron (scavengers of O2.(-)), Na-benzoate, mannitol and deferoxamine (scavengers of OH.) caused a substantial decrease in the rate of HPD photobleaching in EAC cells. In these cells, the inhibitory effects of Na-benzoate, mannitol and deferoxamine on the photodegradation of HPD correlated well with suppression of the OH. generation, a highly active oxidizer. In EAC cells, the glutathione redox cycle and CAT (scavengers of H2O2) as well as Cu/Zn-SOD was found to suppress the photoinduced degradation of HPD. It was also established that HPD can directly scavenge H2O2 and oxygen free radicals; in a phosphate buffer its second-order rate constants were measured as 5.51+/-0.32 x 10(3)M(-1)s(-1) (for the reaction with O2.(-)), 5.08+/-0.31 x 10(4)M(-1)s(-1) (for H2O2), and 3.44+/-0.08 x 10(10)M(-1)s(-1) (for OH.). Thus, our data suggest that OH. could be one of the main oxidants mediating the photobleaching behavior of HPD in malignancies. Studies showed that photoexcited moieties of HPD can oxidize cell proteins with the formation of protein peroxides (PPO), which currently are regarded as a new form of ROS. Model experiments suggest that PPO could also participate in bleaching of HPD in tumors treated with PDT. It was found that HPD may destroy in tumor cells after cessation of photoirradiation and that this event is largely mediated by the presence of H2O2, a precursor of OH(.).
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PMID:Active oxygen intermediates in the degradation of hematoporphyrin derivative in tumor cells subjected to photodynamic therapy. 1876 Jun 22