Yuji Sato

alpha-Tocopherol transfer protein (alphaTTP), a product of the gene which causes familial isolated vitamin E deficiency, plays an important role in determining the plasma vitamin E level. We examined the structural characteristics of vitamin E analogs required for recognition by alphaTTP. Ligand specificity was assessed by evaluating the competition of non-labeled vitamin E analogs and alpha-[3H]tocopherol for transfer between membranes in vitro. Relative affinities (RRR-alpha-tocopherol = 100%) calculated from the degree of competition were as follows: beta-tocopherol, 38%; gamma-tocopherol, 9%; delta-tocopherol, 2%; alpha-tocopherol acetate, 2%; alpha-tocopherol quinone, 2%; SRR-alpha-tocopherol, 11%; alpha-tocotrienol, 12%; trolox, 9%. Interestingly, there was a linear relationship between the relative affinity and the known biological activity obtained from the rat resorption-gestation assay. From these observations, we conclude that the affinity of vitamin E analogs for alphaTTP is one of the critical determinants of their biological activity.

alpha-Tocopherol transfer protein was purified from the 10,000 x g supernatant of rat liver. Two isoforms of the transfer protein exist, of which the isoelectric points are 5.0 and 5.1 as determined by chromatofocusing. These two isoforms have the same molecular weight; both showed molecular weight of approx. 30,500 on SDS-polyacrylamide gel electrophoresis. They cannot be distinguished from each other by amino acid composition or substrate specificity.

PURPOSE: To evaluate the efficacy and toxicity of docetaxel in combination with a novel oral 5-fluorouracil analogue S-1 for patients with advanced or recurrent gastric cancer. EXPERIMENTAL DESIGN: Patients with advanced or recurrent adenocarcinoma of the stomach and up to one previous chemotherapy regimen were treated with i.v. docetaxel 40 mg/m2 on day 1 and oral S-1 80 mg/m2/d on days 1 to 14 every 3 weeks. RESULTS: Forty-eight patients (median age, 65 years; range, 25-75 years) received a total of 272 treatment cycles (median, 4; range, 1-17). No complete responses and 27 partial responses were observed for an overall response rate of 56.3% [95% confidence interval (95% CI), 38-66%]. Eighteen patients (37.5%) had stable disease and three patients (6.3%) had progressive disease as best response. The tumor control rate (complete response + partial response + stable disease) was 93.8% (95% CI, 83-98%). Median overall survival was 14.3 months (95% CI, 10.7-20.3 months) and median time to tumor progression was 7.3 months (95% CI, 4.3-10.0 months). The most common grade 3 to 4 hematologic toxicities were neutropenia (58.3%), leukopenia (41.7%), febrile neutropenia (8.3%), and anemia (8.3%). The most common grade 3 nonhematologic toxicities included anorexia (14.6%), stomatitis (8.3%), and nausea (6.3%). No grade 4 nonhematologic toxicities were reported and all treatment-related toxicities were resolved. CONCLUSION: Docetaxel/S-1 combination is highly active and well tolerated in advanced or recurrent gastric cancer. Further investigation in randomized studies is warranted.

The correlation of titers of specific serum immunoglobulin G antibodies against two antigens, pertussis toxin (PT), and filamentous hemagglutinin (FHA), which are the main components of pertussis vaccine in Japan, with mouse protectivity was examined by both intracerebral and aerosol challenge systems with virulent Bordetella pertussis cells. Titer of the antibodies was calculated from the enzyme-linked immunosorbent assay (ELISA) unit given arbitrarily to reference antibodies. PT antibody titer which protected 50% of mice was indistinguishable in both active immunization followed by intracerebral challenge and passive immunization followed by aerosol challenge. The 50% effective dose was 23 ELISA U/ml in the former mice and 24 ELISA U/mouse in the latter. In the intracerebral challenge system, FHA did not elicit a protective response but was very helpful for PT as an immunizing antigen. When anti-FHA immunoglobulin G coexisted with anti-PT immunoglobulin G in mice, the 50% effective dose of PT antibody was 4.4 or 10 ELISA U/mouse in intracerebral or aerosol challenge systems, respectively. In this active immunization system, pertussis toxoid of 1 micrograms or 0.1 microgram/mouse produced PT antibody of ca. 20 or 5 ELISA U/ml, respectively. It was concluded that pertussis toxoid or its antibody was much more potent than Formalin-treated FHA or its antibody; Formalin-treated FHA or its antibody was helpful when it was administered with pertussis toxoid toxoid or its antibody, however.