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Mono-L-aspartyl chlorin e6 (NPe6) and hematoporphyrin derivative (HpD) in photodynamic therapy administered to a human cholangiocarcinoma model.
- Source :
-
Cancer [Cancer] 1998 Jan 15; Vol. 82 (2), pp. 421-7. - Publication Year :
- 1998
-
Abstract
- Background: Despite their relatively localized nature, the therapy for surgically unresectable cholangiocarcinomas has been largely unsuccessful. Photodynamic therapy is a promising technique for both curative and palliative treatment of this malignancy. The effectiveness of a potential new photosensitizer, mono-l-aspartyl chlorin e6 (NPe6), was compared with that of a traditional drug, hematoporphyrin derivative (HpD), in photodynamic therapy administered to a human cholangiocarcinoma model.<br />Methods: An established cholangiocarcinoma cell line was inoculated subcutaneously in the left back of male nude mice age 8 weeks. After a predetermined tumor size was reached, the mice were randomly assigned to either a control group or an experimental group. Experimental tumor-bearing mice received either HpD (5 mg/kg or 10 mg/kg) or NPe6 (2 mg/kg, 5 mg/kg, or 8 mg/kg) followed by photoradiation. HpD and NPe6 were administered intraperitoneally at 24 and 2 hours, respectively, prior to light exposure. Photoradiation was conducted using a xenon-mercury arc lamp with a 405-650 nm filter at a light flux of 80 J/cm2. Tumor response was assessed by serial tumor volume measurements.<br />Results: Control mice showed an estimated mean tumor volume doubling rate of 9.0 days. Triaxial tumor measurements correlated well with autopsy measurements (correlation coefficient = 0.9). Overall differences in tumor volume reduction were detected (P < 0.001) among the three groups: HpD, NPe6, and controls (photoradiation only, HpD only, or NPe6 only). The degree of tumor volume reduction was superior for dosages of NPe6 compared with all dosages of HpD (P < 0.05). Although a dose effect was detected (P < 0.05) for HpD and separately for NPe6, a consistent dose-response relationship was not observed for either. Inhibition of tumor regrowth was better for NPe6 compared with HpD. The depth of tissue injury was significantly increased (P < 0.05), by 67%, for 5-8 mg/kg of NPe6 compared with 5-10 mg/kg of HpD. The duration of cutaneous photosensitization was also decreased for NPe6 compared with HpD.<br />Conclusion: Photodynamic therapy with HpD or NPe6 was effective inducing tumor regression in the cholangiocarcinoma model in this study. At the dosages studied, NPe6 appeared to induce greater tumor regression than HpD, with decreased tumor regrowth and duration of cutaneous photosensitization.
- Subjects :
- Animals
Antineoplastic Agents administration & dosage
Antineoplastic Agents adverse effects
Cholangiocarcinoma pathology
Disease Models, Animal
Hematoporphyrin Derivative administration & dosage
Hematoporphyrin Derivative adverse effects
Humans
Injections, Intraperitoneal
Male
Mercury
Mice
Mice, Nude
Palliative Care
Photosensitivity Disorders etiology
Photosensitivity Disorders prevention & control
Photosensitizing Agents administration & dosage
Photosensitizing Agents adverse effects
Porphyrins administration & dosage
Porphyrins adverse effects
Random Allocation
Remission Induction
Skin drug effects
Soft Tissue Neoplasms drug therapy
Soft Tissue Neoplasms pathology
Xenon
Antineoplastic Agents therapeutic use
Cholangiocarcinoma drug therapy
Hematoporphyrin Derivative therapeutic use
Hematoporphyrin Photoradiation adverse effects
Photochemotherapy adverse effects
Photosensitizing Agents therapeutic use
Porphyrins therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 0008-543X
- Volume :
- 82
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Cancer
- Publication Type :
- Academic Journal
- Accession number :
- 9445202