MCF-7 human breast cancer cells selected in Adriamycin in the presence of verapamil developed a multidrug resistant phenotype, which was characterized by as much as 100,000-fold resistance to mitoxantrone, 667-fold resistance to daunorubicin, and 600-fold resistance to doxorubicin. Immunoblot and PCR analyses demonstrated no increase in MDR-1 or MRP expression in resistant cells, relative to parental cells. This phenotype is similar to one previously described in mitoxantrone-selected cells. The cells, designated MCF-7 AdVp, displayed a slower growth rate without alteration in topoisomerase II alpha level or activity. Increased efflux and reduced accumulation of daunomycin and rhodamine were observed when compared to parental cells. Depletion of ATP resulted in complete abrogation of efflux of both daunomycin and rhodamine. No apparent alterations in subcellular daunorubicin distribution were observed by confocal microscopy. No differences were noted in intracellular pH. Molecular cloning studies using DNA differential display identified increased expression of the alpha subunit of the amiloride-sensitive sodium channel in resistant cells. Quantitative PCR studies demonstrated an eightfold overexpression of the alpha subunit of the Na+ channel in the resistant subline. This channel may be linked to the mechanism of drug resistance in the AdVp cells. The results presented here support the hypothesis that a novel energy-dependent protein is responsible for the efflux in the AdVp cells. Further identification awaits molecular cloning studies.

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Abstract. Adalia bipunctata is a well-known predaceous ladybird distributed in Europe, Central Asia and North America. This spe cies has not been recorded in Japan. Recently, we found this species in the Osaka Bay area in central Japan, and assume that it was imported with goods such as timber by ships. We studied the life history and the distribution in the Osaka Bay area since the initial discovery. The larvae and adults preyed on aphids (mainly, Periphyllus viridis) on trees such as Acer buergerianum and Rhaphiolepis umbellata. The over-wintered adults appeared in March and laid eggs. The adults emerged in spring, and were in the rolled leaves throughout the rest of the year. Thus, in Japan this ladybird is univoltine with long inactivity in adult. The life history of Japa nese population of A. bipunctata differs considerably from other areas where populations are multivoltine. The developmental threshold was estimated to be 6.3°C and the sum of effective temperatures was 322.6 day-degrees for the period from egg to adult emergence. Predation on prepupae of A. bipunctata by the larvae of native species such as Harmonia axyridis was observed occa sionally.

Our study indicated that MMP-2 and MMP-9 expressions are prognostic factors predicting the recurrence of meningioma, independent of proliferative potential.