Biomedical subjects

P A De Witte

Publications and source records attributed to P A De Witte.

7 recordsLinked to original sources

PubMed2001

Synergistic effect of photodynamic therapy with hypericin in combination with hyperthermia on loss of clonogenicity of RIF-1 cells.

Hypericin is a natural photosensitizer produced in plants of the genus Hypericum. The compound exhibits a potent phototoxicity both in vitro and in vivo. In the present study we investigated the effect of hypericin-mediated PDT on hyperthermia (43 degrees C) in RIF-1 cell line. Our results demonstrated a synergistic effect on loss of cell clonogenicity when PDT exposure was followed immediately by hyperthermia. This synergistic effect was diminished by introducing an interval (at 37 degrees C) between the two treatments. Furthermore, it was found that combining PDT treatment with hyperthermia could significantly enhance the cell death by necrosis as indicated by morphological examination and significant loss of membrane integrity. Our data suggest that the common cell membrane damage by both PDT and hyperthermia is likely to be responsible for this synergistic effect.

Animals↗

PubMed2001

In vivo photodynamic activity of hypericin in transitional cell carcinoma bladder tumors.

In a recent clinical study, we showed that hypericin accumulates selectively in urothelial lesions of the bladder following intravesical administration of the compound in patients. This observation infers that hypericin, a potent photosensitizer, could be used as a selective photodynamic therapy (PDT) tool against superficial bladder cancer. In the present study we investigated the in vivo PDT activity of hypericin in transition cell carcinoma (TCC) tumors of the bladder. Both the distribution and tumor PDT response were carried out using subcutaneous heterotopic AY-27 TCC tumors in syngeneic rats. For both PDT and distribution studies, hypericin (1 or 5 mg/kg) was injected intravenously 0.5, 6 or 24 h before PDT or distribution evaluation. The data show that hypericin is a potent photosensitizer in the treatment of TCC tumors in vivo and that the interval between drug administration and photo-irradiation has a dramatic effect on the PDT outcome. Using a 0.5 h interval between drug administration and photo-irradiation the tumor regrowth study indicated that no tumor mass could me measured 9-10 days after PDT. On the contrary, lengthening the time interval between drug administration and photo-irradiation resulted in a gradual loss of PDT efficiency in these tumors. For instance, while the 6 h drug interval protocol produced a moderate PDT activity in which the tumor sizes decreased to about 50% of their original sizes 11-16 days after photo-irradiation, the 24 h interval protocol was even less effective. The distribution data indicate that the PDT efficiency of hypericin in TCC tumors corresponded to the plasma concentrations rather than to the over all concentrations in the tumor. It is therefore conceivable that the mechanism of PDT efficacy of hypericin in TCC tumors is through indirect (vascular effects) rather than through direct effects (cellular destruction) of hypericin in these tumors. In conclusion, our data indicate that hypericin is a potent photosensitizer against AY-27 TCC tumors and that the PDT efficacy of hypericin is largely determined by photosensitizer distribution in the tumor at the time of photo-irradiation.

Animals↗

PubMed2000

Fluorescence detection of flat bladder carcinoma in situ after intravesical instillation of hypericin.

PURPOSE: We determined the sensitivity and specificity of detecting flat bladder carcinoma in situ through fluorescent detection after intravesical hypericin instillations. MATERIALS AND METHODS: The study included 40 patients, of whom 26 presented with macroscopic visible tumor, 9 had a positive cytology without visible tumor and 5 underwent cystoscopy after bacillus Calmette-Guerin instillations (4) or radiotherapy (1). We instilled 40 ml. of a 8 microM. solution of hypericin intravesically for at least 2 hours. Fluorescence excitation with blue light was effective up to 16 hours after termination of the instillation. RESULTS: All visible papillary tumors showed red fluorescence. In addition, 134 flat fluorescent areas were detected. Analysis of 281 biopsies from flat bladder wall indicated 93% sensitivity and 98.5% specificity for detecting carcinoma in situ. Visible lesions resulting from radiotherapy, chemotherapy or immunotherapy did not show any fluorescent signs and, therefore, did not induce false-positive readings. There were no signs of photobleaching during inspection and resection. CONCLUSIONS: We report a simple yet comprehensive endoscopic method for early detection of bladder cancer, including carcinoma in situ. Hypericin induced fluorescence has a high sensitivity and specificity for detection of bladder transitional cell carcinoma, papillary and flat carcinoma in situ. When carcinoma in situ is suspected, this technique is highly recommended.

Administration, Intravesical↗

PubMed1999

Confluence dependent resistance to photo-activated hypericin in HeLa cells.

Hypericin is a natural photo-active pigment produced by plants of the genus Hypericum. The compound exhibits a potent photocytotoxic activity in vitro and in vivo. Using HeLa cells we further investigated whether the photocytotoxic in vitro effect of hypericin is influenced by the cell density. It was demonstrated that hypericin-induced photocytotoxicity in HeLa cells depends significantly on the amount of cells in culture, as low cell density cultures were more responsive to photodynamic therapy (PDT) than confluent or hyperconfluent cell cultures. This confluence dependent resistance (CDR) can be explained in terms of a decrease in hypericin cellular uptake. The phenomenon is not caused by the depletion of hypericin from the medium by high-density cell cultures since the extra-cellular availability of the drug is not altered by the increase in cell density and does not appear to be a limiting factor. Importantly, since confluent or hyperconfluent cell cultures can better mimic the high cell density of the solid tumour, CDR should be taken into consideration whenever resistance of solid tumours to PDT with hypericin is observed.

Anthracenes↗

PubMed1990

Ethanol and opiate decrease the axonal transport of substance-P like immunoreactive material in rat vagus-nerves.

Since an enhanced retrograde axonal transport of receptor-bound opiate was observed in the ligated vagus nerves of rats treated chronically with alcohol, we decided to look at the anterograde axonal transport of substance P in the same experimental conditions and, after opiate administration. From 1 day up to 24 days' treatment with alcohol, we observed a decrease in the accumulation of substance P like immunoreactive material (SPLM) in rat ligated vagus nerves. Acute administration of lofentanil, an mu opiate agonist, caused the same reduction of anterograde axonal transport of SPLM and this effect could be prevented by naloxone. When naloxone or bezitramide, an opiate agonist, was given during the alcoholization period, the preference for alcohol in a choice test was reduced or prevented suggesting that opioid peptides are probably involved in chronic alcoholism. The present results support the idea that a common denominator could exist in drug addition and in chronic alcoholism and that substance P may be directly or indirectly involved.

Analgesics↗

PubMed1987

Enhanced axonal transport of receptor-bound opiate in ethanol-treated rats.

The retrograde transport of receptor-bound opiate was markedly enhanced in the vagus nerves of rats housed for 25 days in an atmosphere of ethanol vapor. This increase disappeared after 8 days of withdrawal as did the animal preference for ethanol. In contrast, the axonal transport of muscarinic receptors in sciatic nerves was slightly reduced. This provides more evidence for the idea that chronic alcoholization and morphine addiction share a common denominator and that the retrograde transport of receptor-bound signal molecules represents a link between the synapses and the cell-body of neurones.

Animals↗

PubMedDate not supplied

Antitumour activity of photosensitized hypericin on A431 cell xenografts.

The in vivo antitumour activity of the natural photosensitizer hypericin was evaluated. Athymic nude mice xenografted with A431 cells were intraperitoneally administered with different hypericin doses and the tumours were locally irradiated 2 h later with white light (180 J/cm2) using a cold light source. When treatment was started one day after tumour inoculation, a dose-dependent antitumour effect was observed in light-treated animals. Complete inhibition of the tumour growth was achieved with 2.5 mg/kg hypericin. When the efficacy of a single hypericin dose (5 mg/kg) followed by a single light treatment on established tumours (60 mm3) was investigated, an 80% reduction in tumour mass was seen. Furthermore, an accumulation of the photosensitizer in A431 xenografts was observed after local light irradiation. Our results strongly suggest that hypericin holds promise as a new, safe, efficient and selective PDT photosensitizer.

Animals↗