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Shinya Hayasaka

Publications and source records attributed to Shinya Hayasaka.

6 recordsLinked to original sources
PubMed2004

Novel camptothecin analogues that circumvent ABCG2-associated drug resistance in human tumor cells.

Irinotecan (7-ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxycamptothecin; CPT-11) is a widely used potent antitumor drug that inhibits mammalian DNA topoisomerase I (Topo I); however, overexpression of ABCG2 (BCRP/MXR/ABCP) can confer cancer cell resistance to SN-38, the active form of CPT-11. We have recently demonstrated that plasma membrane vesicles prepared from ABCG2-overexpressing PC-6/SN2-5H cells transported SN-38 and its glucuronide conjugate in an ATP-dependent manner (Nakatomi et al., Biochem Biophys Res Commun 2001;288:827-32). In the present study, we have characterized a total of 14 new camptothecin (CPT) analogues with respect to both the inhibition of Topo I and the substrate specificity of ABCG2. All of the tested CPT analogues, which have different substitutions at positions 10 and 11, strongly inhibited the Topo I activity in a cell-free system, as did SN-38. Their antitumor activities in the SN-38-resistant PC-6/SN2-5H2 cell line greatly varied, however, being correlated with intracellular accumulation levels. We have examined ATP-dependent transport of those CPT analogues by using plasma membrane vesicles prepared from both PC-6/SN2-5H2 cells and ABCG2-transfected HEK-293 cells. Based on the substrate specificity of ABCG2 thus evaluated, it is strongly suggested that CPT analogues with high polarity are good substrates for ABCG2 and are therefore effectively extruded from cancer cells. In this context, to circumvent ABCG2-associated drug resistance, low-polarity CPT analogues are considered to be potent lead compounds. The present study provides a practical approach to discover new CPT-based drugs for the chemotherapy of drug-resistant human cancer.

ATP Binding Cassette Transporter, Subfamily G, Mem↗
PubMed2003

Simple non-ion-paired high-performance liquid chromatographic method for simultaneous quantitation of carboxylate and lactone forms of 14 new camptothecin derivatives.

SN-38 (7-ethyl-10-hydroxycamptothecin) is an active metabolite derived from the semi-synthetic compound camptothecin (CPT) named Irinotecan (CPT-11). The antitumor activity of SN-38 is 1000-fold more potent than the parent CPT-11. Fourteen new derivatives of camptothecin have recently been developed by Yakult Honsha (Tokyo, Japan). Here we describe a simple and cost-effective high-performance liquid chromatography (HPLC) method without an ion-pairing agent, which allows the simultaneous determination of both lactone and carboxylate forms of SN-38 and other camptothecin derivatives. A weak linear relationship between the HPLC retention factors (ln k') and the cellular concentrations of these compounds was observed. These results suggest that low-polarity compounds easily accumulate in cancer cells and may circumvent drug resistance. The HPLC analysis herein described is expected to greatly assist in derivative synthesis and chemical modification of camptothecin-based antitumor drugs.

Camptothecin↗
PubMed2003

Analyses of fatal cases of Kawasaki disease in Japan using vital statistical data over 27 years.

BACKGROUND: Chronological changes in mortality and case fatality rates from Kawasaki disease covering an extended period in Japan are still unknown. METHODS: We analyzed 679 deaths of patients in Japan whose underlying cause was Kawasaki disease, by using the data of vital statistics between 1972 and 1998. RESULTS: The male-to-female ratio of the number of deaths was 2.07 and the mean age at death in males was higher. Two unusual increases in the epidemic years, 1982 and 1986, were observed in the chronological changes of the number of deaths. The mortality rate of males was higher than that of females, with a few exceptional years, and the annual mortality rates were high in three epidemic years. The age-specific mortality rate was highest in infants under one year of age. Prefectures with high mortality rate clustered in some regions. The case fatality rate decreased annually, declining to as low as 0.2% among those who were born in 1986 and thereafter; and unusual increases in the case fatality rate affected by these three epidemic years were not repeated. CONCLUSIONS: The case fatality rate from Kawasaki disease in Japan decreased during the 27 years of observation: improvements in treatment might account for this.

Age Factors↗
PubMed2003

Job characteristics and serum lipid profile in Japanese rural workers: the Jichi Medical School Cohort Study.

To observe the association between adverse psychosocial job characteristics, measured by the Karasek job demand-control questionnaire, and a lipid profile, cross-sectional analyses were performed for a Japanese rural working population. The study population comprised 3,333 male and 3,596 female actively employed workers, aged 65 years and under. Among men, higher psychological demands were associated with high total cholesterol levels, with an adjusted difference from the top to bottom tertiles of 3.3 mg/dl (F = 3.03; p = 0.048). High demands were also positively associated with the total/HDL cholesterol ratio (F = 3.94; p = 0.020). Neither job control nor job strain (the ratio of demands to control) was associated with any of the lipid levels in either gender. A psychologically demanding job may be associated with an unfavorable lipid profile, but the impact of job strain on atherogenic lipids is negligible.

Adult↗
PubMed2002

[Incidence rates for accidents associated with bathing services for the aged in Japan].

OBJECTIVES: To reveal incidence rates for accidents with bathing services for the aged in Japan. DESIGN: A postal questionnaire survey. PARTICIPANTS: Of 444 councils providing bathing services, we sent a postal questionnaire to 102 which had experienced accidents. MEASUREMENTS: Timing of the start of provision of bathing services, the total number of bathing services in 2000, and the number of accidents due to bathing services during the last five years in both home-visiting and facility bathing services. ANALYSES: In addition we estimated the total number of bathing services per one council for five years to yield the incidence of accidents per 10,000 bathings for the 444. Finally we estimated the total number of accidents due to bathing services in Japan. RESULT: Replies were received from 95 (93%) councils. The total number of bathings per council over five years was 4245.0 +/- 4637.7 for home-visits, and 22,235.3 +/- 37,259.4 in facilities. The incidence rates for accidents per 10,000 bathings in 95 councils which experienced accidents were 1.33 and 0.28, respectively. The rates for all 444 councils were 0.204 and 0.067, and the total numbers of accidents due to bathing services were estimated to be 63.1 in home-visits and 149.1 in facilities throughout Japan. CONCLUSION: These results indicated that providers' attention should be drawn to the higher incidence of accidents with home-visit than with facility bathing services.

Accidental Falls↗