picibanil and Necrosis

This study investigated the combined effect of photodynamic therapy (PDT) using high power laser irradiation (HPL), which generates both a hyperthermic and a photodynamic effect, and OK-432 on NR-S1 mouse squamous cell carcinoma. The photosensitizer (haematoporphyrin oligomers 20 mg/kg BW) was injected to the mice intraperitoneally 48 h before laser irradiation. OK-432 was injected into the tumour 3 h prior to laser irradiation. The experimental protocols consisted of HPL-PDT with or without OK-432, low power laser PDT with or without OK-432, HPL alone and OK-432 alone, and a control group. The tumour necrotic area was determined, and tumour sizes were measured 3, 7 and 10 days after each protocol. The anti-tumour effect of HPL-PDT was enhanced by preadministration with OK-432. Treatment with OK-432 alone or hyperthermic HPL irradiation presented little anti-tumour effect. HPL-PDT in combination with OK-432 topically administered 3 h before photo-irradiation is considered to be a promising therapeutic modality.

Topics: Animals; Antineoplastic Agents; Carcinoma, Squamous Cell; Combined Modality Therapy; Hyperthermia, Induced; Male; Mice; Mice, Inbred C3H; Necrosis; Photochemotherapy; Picibanil

Biological response modifier antitumor effects are enhanced by the activation of the host defense mechanisms. We have investigated the antitumor effect of photodynamic therapy (PDT) and/or local administration of a biological response modifier, the streptococcal preparation OK-432, on transplanted NR-S1 mouse squamous cell carcinoma. Hematoporphyrin oligomers (20 mg/kg body weight) were used to photosensitize PDT. A pulsed Nd:YAG dye laser, tuned at 630 nm, was used as the light source. The laser power was 15 mJ cm(-2) pulse(-1), and the irradiation time was 40 min. The photosensitizer was injected intraperitoneally 48 h before laser irradiation. Where used, OK-432 was injected into the tumor either 3 h prior to PDT or immediately afterwards. The antitumor effects were evaluated 48 h after each protocol by (a) estimating the area of tumor necrosis (%) in hematoxylin/eosin-stained specimens, and (b) bromodeoxyuridine immunohistochemistry. Furthermore, the tumor sizes were evaluated 3, 7 and 10 days after each protocol, and the survival time after each protocol was evaluated as well. The antitumor effect of PDT was enhanced by administration of OK-432 3 h before PDT, whereas the administration of OK-432 immediately after PDT did not potentiate a PDT antitumor effect. Treatment with OK-432 alone had little effect on tumors. Photodynamic therapy in combination with local administration of OK-432 3 h before PDT is considered to be a useful treatment modality.

Topics: Animals; Antineoplastic Agents; Bromodeoxyuridine; Carcinoma, Squamous Cell; Combined Modality Therapy; Immunohistochemistry; Male; Mice; Mice, Inbred C3H; Necrosis; Neoplasm Transplantation; Neutrophils; Photochemotherapy; Picibanil; Time Factors; Treatment Outcome; Tumor Cells, Cultured

Hyperthermia is being investigated as a cancer treatment. Many of its basic mechanisms, particularly those related to cell killing, are still poorly understood. We used a transplanted squamous cell carcinoma cell line to investigate the therapeutic effect of hyperthermia. In particular, we examined the effect of OK-432 (biological response modifier) on hyperthermia-induced apoptosis. In the hyperthermia only group the most extensive necrosis occurred on day 3 (70.3%), and the apoptosis index also was highest on that day (69.3). These results suggest that the induction of apoptosis is closely related to the cell death caused by hyperthermia. The percent of necrosis was significantly higher in the groups given hyperthermia and combined OK-432 and hyperthermia treatment than in the OK-432 group (p < 0.05). The apoptosis index was significantly lower in the combined OK-432 and hyperthermia treatment group than in the hyperthermia only group, indicative that the antitumor effect of combined hyperthermia and OK-432 therapy is not ascribable to the induction of apoptosis.

Topics: Animals; Antineoplastic Agents; Apoptosis; Carcinoma, Squamous Cell; Combined Modality Therapy; Hyperthermia, Induced; Male; Mice; Mice, Inbred C3H; Necrosis; Picibanil

We investigated the effects of OK432, recombinant human interferon alpha A/D (rIFN alpha A/D) and a combination of these drugs on murine acute myocarditis due to encephalomyocarditis virus. Mice were administered 1 KE of OK432 and 10(4)U/g of rIFN alpha A/D starting 24 hr after viral inoculation for 14 days. The survival rate of mice having the combination therapy was significantly higher than that of untreated mice on day 21 (15 of 20 vs. 6 of 20, P less than .001), whereas the viral titer in the heart, the heart weight/body weight ratio and the scores for myocardial inflammation and necrosis were significantly lower. On the other hand, therapy with OK432 or rIFN alpha A/D individually improved neither the survival rate nor the extent of myocardial damage. The natural killer cell activity in the combination therapy mice on day 3 after infection was significantly increased in comparison with untreated mice (46.2 +/- 5.5 vs. 37.7 +/- 2.8%, P less than .01), and the cytotoxicity of peritoneal macrophages was increased (45.0 vs. 26.7%). Thus, the combination therapy of OK432 and rIFN alpha A/D was more effective than the therapy with OK432 alone or rIFN alpha A/D alone against acute viral myocarditis when the treatment was started early after infection, and the stimulation of host immunologic response by OK432 may be important for this combination therapy.

Topics: Animals; Body Weight; Cytotoxicity, Immunologic; Drug Therapy, Combination; Encephalomyocarditis virus; Female; Heart; Interferon Type I; Killer Cells, Natural; Macrophages; Mice; Mice, Inbred C3H; Myocarditis; Myocardium; Necrosis; Picibanil; Recombinant Proteins