Phthalocyanine-dyed fibers adsorb allergenic proteins.

Phthalocyanine (Pc)-dyed fiber is reported to reduce atopic symptoms in some patients when they use underwear made of the fiber. We investigated the adsorption of allergens on Pc-fiber. Pc-fiber trapped house dust/pollen/food allergens with varied molecular weight and pI. The adsorbed allergens were released in the presence of mild detergent. Pc-fiber did not change the molecular weight or disulfide bonding of the allergens. These observations imply that Pc-fiber is applicable as an "allergen trap" for a wide variety of products.

Regulation of dihydropyrimidine dehydrogenase and pyrimidine nucleoside phosphorylase activities by growth factors and subsequent effects on 5-fluorouracil sensitivity in tumor cells.

Dihydropyrimidine dehydrogenase (DPD) and pyrimidine nucleoside phosphorylase (PyNPase) are the first and rate-limiting enzymes that regulate 5-fluorouracil (5-FU) metabolism, and tumoral DPD activity appears to be a promising predictor of 5-FU sensitivity. However, the regulatory mechanisms determining these enzyme activities have not been fully understood. We investigated the biological effects of epidermal growth factor (EGF) and transforming growth factor (TGF)-alpha on cell growth and tumoral DPD and PyNPase activities, and the subsequent effects on 5-FU sensitivity in uterine cervical carcinoma SKG-IIIb cells. The treatment of tumor cells with EGF or TGF-alpha resulted in a concentration-dependent increase in tumor cell growth and PyNPase activity, whereas tumoral DPD activity was inhibited. Their stimulatory effects on tumor cell growth correlated well with PyNPase activity, but were inversely related to DPD activity (P < 0.01). 5-FU sensitivity of tumor cells increased in the presence of EGF or TGF-alpha. These growth factors were shown to stimulate the first, rate-limiting enzyme activity in 5-FU anabolism and to inhibit that in 5-FU catabolism, leading to enhancement of the antiproliferative action of 5-FU at achievable therapeutic levels. The tumor environmental factors, EGF and TGF-alpha, may act as intrinsic regulators of DPD and PyNPase activities that affect the 5-FU sensitivity of individual tumors.

In vitro combination effect of 5-fluorouracil and cisplatin on the proliferation, morphology and expression of Ki-67 antigen in human gastric cancer cells.

The combination effect of 5-fluorouracil (5-FU) and cisplatin was examined in terms of the proliferation, morphology and expression of Ki-67 antigen, and propidium iodide (PI) staining using four cultured human gastric cancer cell lines, and we assessed how such activity was affected by the exposure time and the timing of treatment. MKN-1, MKN-28, MKN-45 and MKN-74 cells were exposed to various concentrations of 5-FU for 72 h and cisplatin for 8 or 72 h. At IC50, MKN-28 cells were more sensitive to 5-FU than other cell lines, whereas MKN-1 and MKN-45 cells were more sensitive to cisplatin than other cell lines. The cell growth-inhibitory activity of cisplatin was found to be 'area under the curve' dependent. When 5-FU and cisplatin were combined simultaneously, the combination effect was higher than that of 5-FU or cisplatin alone. On the other hand, when cisplatin was applied before 5-FU, there was no potentiation of the cell growth-inhibitory activity by combination treatment. In 5-FU-treated MKN-74 cells, the size, morphology and PI staining of nuclei were almost the same as those of the untreated cells, and the expression of Ki-67 antigen was less than that of the untreated cells. In cisplatin-treated MKN-74 cells, the size of cells and nuclei was larger than that of the untreated cells and fragmentation of nuclei was observed. The expression of Ki-67 antigen was less than the untreated cells but more than that of 5-FU-treated cells. In the cells treated with 5-FU and cisplatin in combination, the above changes were an intermediate of those of 5-FU-treated cells and cisplatin-treated cells. In conclusion, the cell growth-inhibitory activity of 5-FU and cisplatin against gastric cancer cells was potentiated by the combined treatment with 5-FU and cisplatin simultaneously, but not with cisplatin followed by 5-FU.

A case of advanced gastric cancer complicated by severe toxicity induced by a combination of tegafur, uracil and mitomycin C, and associated with abnormal pharmacokinetics.

A 60-year-old female patient with gastric cancer and lymph node and liver metastases was treated with a combination of tegafur and uracil (UFT) (375 mg/m2/day) and mitomycin C (MMC) (5 mg/m2 once weekly). On day 15, when diarrhea appeared, chemotherapy was stopped immediately. On day 21, the WBC decreased to 900/microl and high fever developed. Despite treatment with granulocyte colony-stimulating factor and antibiotics, leukopenia persisted and the patient went into septic shock on day 26. On day 34, WBC increased to 5,400/microl and she recovered, with reduction in the size of the lymph node and liver metastases. Pharmacokinetic examination after intravenous injection of low-dose MMC (0.5 mg/m2) showed a markedly high peak plasma concentration (PPC), a large area under the time-versus-concentration curve (AUC) and reduced clearance. Similarly, oral administration of UFT (tegafur 300 mg/body) produced a relatively higher PPC and a larger AUC of 5-fluorouracil (FU). The activity of dihydropyrimidine dehydrogenase, the rate-limiting enzyme in the metabolism of FU, in peripheral mononuclear cells was within the normal range (0.265 nmol/min/mg). MMC is believed to have played a large part in inducing the severe toxicity observed in this patient. Physicians should be aware of the possibility of severe toxicity during treatment with UFT and MMC, although details of its incidence and mechanism are unclear.