Anti-tumour activity of photodynamic therapy in combination with mitomycin C in nude mice with human colon adenocarcinoma

Abstract

BrWsh Journ d Caner (1995) 71,[950][951][952][953][954][955][956] 9 © 1995 Stockton Press AJI nghts reserved 0007-0920/95 $12.00 Anti-tumour activity of photodynamic therapy in combination with mitomycin C in nude mice with human colon adenocarcinoma LW Ma, J Moan, HB Steen and V lani Department of BiophYsics, The Institute of Cancer Research, Montebello, 0310 Oslo 3, NorKay.S_ry The interaction of photodynamic therapy (PDT) and a chemotherapeutic drug, mitomycin C (MMC), was investigated using WiDr human colon adenocarcinoma tumours implanted on Balb/c athymic nude mice. The WiDr tumours were treated with PDT alone, MMC alone or with both. It was found that the combined treatment produced a greater retardation in the growth of the WiDr tumour than monotherapy with MMC or PDT. The synergistic effect was especially prominent when PDT was used in combination with a low dose of MMC (1 mglkg-'), since treatment of I mg kg-' MMC alone had no effect on the tumour. The anti-tumour activity of PDT was found to be increased with MMC of 5 mg kg-'. The response of normal skin on mice feet to PDT slightly greater when PDT was combined with 5 mg kg-' MMC than when PDT was applied alone, while no detectable additional effect on skin photosensitivity was observed when PDT was combined with I mg kg- ' MMC. An enhanced uptake of Photofrin in tumours was found 12 h and 24 h after administration of MMC. The effect of MMC on the cell cycle distribution of cell dissociated directly from the tumours was studied. The results suggest that the increased susceptibility to photoinactivation of Photofrinsensitised tumours may be due to MMC-induced accumulation of the tumour cells in S-phase.

Optimizing Photodynamic Therapy:In vivoPharmacokinetics of Liposomalmeta-(Tetrahydroxyphenyl)Chlorin in Feline Squamous Cell Carcinoma

“…The bioavailability in the skin was similar for both photosensitizers (P = 0.305). The AUC 16 Photosensitizer concentration in plasma/urine. In the m-THPC group, mean and median maximal m-THPC levels of 431.38 and 458.81 ng/mL plasma were reached during the first 8 hours after injection.…”

“…To determine the plasma concentration of m-THPC, blood samples were obtained 1, 3,6,8,16,24,48, and 72 hours after application of the photosensitizer.…”

“…The owners were told to keep the cats away from direct sunlight for another 10 days. The one cat that developed pronounced skin reactions was, in addition to a very low tumor-to-skin AUC 16 , housed at high altitude and went outside 1 week after injection.…”

Oxygen Effects in Photodynamic Therapy

“…Several methods have been proposed to increase tumor oxygenation: (1) breathing hyperbaric oxygen, (2) using oxygen-carrying fluorocarbons combined with carbogen (95% oxygen) breathing, (3) using nicotinamide injection and carbogen breathing, (4) using oxygen-releasing substances, (5) modulating the oxygen binding capacity of hemoglobin, (6) decreasing the respiration rate, (7) increasing the oxygen solubility, (8) using blood flow modifiers, and (9) destroying hypoxic cells with bioreductive drugs or hypothermia [50]. Several of these methods have been exploited for PDTwith promising experimental and clinical results [51][52][53][54][55][56].…”

The role of low-density lipoprotein receptors in sensitivity to killing by Photofrin-mediated photodynamic therapy in cultured human tumor cell lines

“…Using the fluorescence microscopy [9], the uptake of Photofrin (Wyeth-Lederle, Japan, 50 mg/ml at 37 8C for 1 h in DMEM) into the cells was higher in SCC cells (HSC-2) and relatively higher in adenocarcinoma cells (MKN45) than that in melanoma cells (G361, C32TG). The fluorescence of Photofrin was barely detectable in normal cells (N-1).…”