[The Incidence and Management of Hypersensitivity and Infusion Reactions in an Outpatient Chemotherapy Center].

Hypersensitivity reactions(HSRs)are adverse events that are potentially caused by all anticancer agents. HSRs are unpredictable and can occur at any time, and prompt intervention is needed when symptoms occur. The types of symptoms and their degrees vary with the anticancer agent used and the number of chemotherapy cycles. Here, we evaluated the degree of HSRs and their frequencies in the outpatient chemotherapy center of Gunma University Hospital. Among 55,046 patients, 141 (0.26%)cases of HSRs and 70(0.13%)cases of infusion reactions were identified. Oxaliplatin and docetaxel conferred higher incidences of HRSs, whereas infliximab and rituximab conferred higher incidences of infusion reactions. The most common symptoms were skin reactions. HSRs to oxaliplatin were observed after a median of 7 cycles of chemotherapy, and the number of the patients developing HSRs was the highest during the second cycle of chemotherapy. The incidences of HSRs and the profiles of the anticancer drugs exhibiting higher frequencies of HSRs were similar to those in previous reports. The present study provides valuable information about appropriate management for HSRs depending on the anticancer agents used.

Characterization of a genotype previously designated as CYP2A6 D-type: CYP2A6*4B, another entire gene deletion allele of the CYP2A6 gene in Japanese.

CYP2A6 is known as an enzyme responsible for the metabolism of several clincally used drugs such as tegafur. Previously, we found two novel genotypes of the CYP2A6 gene, D-type and E-type, and the E-type was clarified to be homozygous for the CYP2A6*4A allele. On the other hand, since the D-type was reported to lack regions from at least intron 5 to a part of exon 9 of the CYP2A6 gene, it caused a misunderstanding that the D-type would be a partial CYP2A6 gene-deleted allele. In this paper, we demonstrate that the D-type is a genotype heterozygous for the CYP2A6*4A and another novel entire CYP2A6 gene-deleted allele, CYP2A6*4B, by analyzing a Japanese family including parents genotyped as the CYP2A6*4A/4A and CYP2A6*1A/*4B, respectively.

Development of an enzyme-linked immunosorbent assay for metallothionein-I and -II in plasma of humans and experimental animals.

BACKGROUND: An easy and specific enzyme-linked immunoassay (ELISA) for the determination of metallothionein-1 (MT-1) and 2 (MT-2) simultaneously in serum and other biological specimens in humans and experimental animals has not been developed yet. METHODS: We developed a competitive ELISA, a specific polyclonal antibody against rat MT-2. The epitope mapping of the antibody was conducted using MTs in mouse, rat, rabbit, human and the fragment peptides of human MT-2. MT1/2 and MT-3 knock-out mice and cadmium treated mice were used for the evaluation of the ELISA. Pretreatment method of serum was examined to deplete blocking factors for this assay. RESULTS: The antibody used for this ELISA had the same cross-reactivity with MT in humans and experimental animals. NH2 terminal peptide of MT with acetylated methionine was proved to be the epitope of this antibody. The reactivity of this ELISA system with liver, kidney and brain in MT1/2 knock-out mice was significantly low, but was normal in MT-3 knock-out mouse. The lowest detection limit of this ELISA was 0.6 ng/ml and the added MT-1 was fully recovered from serum. The mean MT concentration in our preliminary study was 23+/-4.6 ng/ml in human serum. Cadmium treatment to mice induced significantly higher amount of MT in serum, liver, kidney and spleen as reported previously by different established methods. CONCLUSION: The proposed competitive ELISA is an easy and specific method for practical use, determining total MT-1 and -2 simultaneously in serum and other biological specimens of human and experimental animals.