Optimal vaccine allocation strategy: Theory and application to the early stage of COVID-19 in Japan.

In this paper, we construct an age-structured epidemic model to analyze the optimal vaccine allocation strategy in an epidemic. We focus on two topics: the first one is the optimal vaccination interval between the first and second doses, and the second one is the optimal vaccine allocation ratio between young and elderly people. On the first topic, we show that the optimal interval tends to become longer as the relative efficacy of the first dose to the second dose (RE) increases.

COVID-19 risk perceptions in Japan: a cross-sectional study.

We conducted a large-scale online survey in February 2023 to investigate the public's perceptions of COVID-19 infection and fatality risks in Japan. We identified two key findings. First, univariate analysis comparing perceived and actual risk suggested overestimation and nonnegligible underestimation of COVID-19 risk.

Three years of COVID-19-related school restrictions and mental health of children and adolescents in Japan.

During the 3 years of the COVID-19 pandemic, Japanese children had to live with strict mitigation measures at school, such as eating school lunches silently and wearing masks during physical exercise classes, even after those mitigation measures have been relaxed worldwide. Excursions and other school events were frequently cancelled, especially in 2020 and 2021. This study conducts a retrospective survey on school experiences to understand how the strict mitigation measures were related to children's mental health and well-being.

Heterogeneous risk attitudes and waves of infection.

Many countries have experienced multiple waves of infection during the COVID-19 pandemic. We propose a novel but parsimonious extension of the SIR model, a CSIR model, that can endogenously generate waves. In the model, cautious individuals take appropriate prevention measures against the virus and are not exposed to infection risk.

Population-Level Immunity for Transient Suppression of COVID-19 Waves in Japan from April 2021 to September 2022.

Multiple COVID-19 waves have been observed worldwide, with varying numbers of positive cases. Population-level immunity can partly explain a transient suppression of epidemic waves, including immunity acquired after vaccination strategies. In this study, we aimed to estimate population-level immunity in 47 Japanese prefectures during the three waves from April 2021 to September 2022.

COVID-19 and output in Japan.

We build a tractable SIR-macro-model with time-varying parameters and use it to explore various policy questions such as when to lift the state of emergency (SOE). An earlier departure from the SOE results in smaller output loss and more deaths in the short run. However, if the SOE is lifted too early, the number of new cases will surge and another SOE may need to be issued in the future, possibly resulting in both larger output loss and more deaths.

[Steroid sulfatase inhibitor].

More than 60 percents of breast cancers occur in post menopausal women and most of their initial stages are hormone dependent. For the treatment of estrogen dependent breast tumors, mainly two treatment tools are available, one is selective estrogen receptor modulator (SERM), and the other is aromatase inhibitor (AI). Although these drugs are clinically valuable, the existence of resistant tumors againt these two treatments is one of the most serious matters.

Expression level of enzymes related to in situ estrogen synthesis and clinicopathological parameters in breast cancer patients.

In order to evaluate the importance of estrogen production in tumor and surrounding tissues, we measured mRNA expression levels of 5 enzymes participating to estrogen synthesis in situ and 4 breast cancer-related proteins in 27 pairs of tumor and non-malignant tissues. Steroid sulfatase (STS) mRNA was more frequently detected in tumor tissues rather than in their non-malignant counterparts. Estrogen sulfotransferase (EST) was constantly expressed with high level not only in tumor tissues but also in their surrounding non-malignant counterparts.

New development in intracrinology of breast carcinoma: therapeutic horizons after aromatase inhibitors.

Aromatase inhibitors have become the gold standard of endocrine therapy in postmenopausal patients with estrogen receptor-positive or estrogen-dependent breast carcinoma, replacing tamoxifen. However, it is true that there are some potential problems to be overcome or improved on regarding aromatase inhibitor treatment of breast cancer. This especially includes the presence of the estrogen receptor-positive patients who do not necessarily respond to aromatase inhibitors, may require other modes of endocrine therapy and develop resistance to aromatase inhibitor in their clinical course, and who may also need alternative modes of suppressing intratumoral estrogen signals or other intracellular signal pathways related to tumor progression or development.

A novel steroidal selective steroid sulfatase inhibitor KW-2581 inhibits sulfated-estrogen dependent growth of breast cancer cells in vitro and in animal models.

We screened a series of 17beta-(N-alkylcarbamoyl)-estra-1,3,5(10)trine-3-O-sulfamate derivatives, and describe here a potent and selective steroid sulfatase (STS) inhibitor with antitumor effects in breast cancer models in vitro and in vivo. In biochemical assays using crude enzymes isolated from recombinant Chinese hamster ovary cells expressing human arylsulfatses (ARSs), one of the best compounds, KW-2581, inhibited STS activity with an IC(50) of 4.0 nM, while > 1000-fold higher concentrations were required to inhibit the other ARSs.

Inhibition of steroid sulfatase activity and cell proliferation in ZR-75-1 and BT-474 human breast cancer cells by KW-2581 in vitro and in vivo.

In the present study, we found that two hormone receptor-positive human breast cancer cell lines, ZR-75-1 and BT-474, naturally expressed steroid sulfatase (STS) protein and had catalytic activity to produce estrone from estrone sulfate (E1S) with a comparable level to those in human breast cancer tissues. E1S at physiological concentrations stimulated the growth of those cells. A novel steroidal STS inhibitor, KW-2581 inhibited the STS activity of ZR-75-1 cells with an IC(50) of 13 nM, a potency equal to or higher than that of the non-steroidal STS inhibitor, 667 COUMATE.

New development in intracrinology of breast carcinoma.

Intratumoral metabolism and synthesis of estrogens as a result of the interactions of various enzymes are considered to play very important roles in the pathogenesis and development of hormone dependent breast carcinoma. Among these enzymes, intratumoral aromatase plays as important role converting serum androgens to estrogens in situ, and serves as a source of estrogen, especially in postmenopausal patients with breast carcinoma. However, other enzymes such as the 17beta-hydroxysteroid dehydrogenase (17beta-HSD) isozymes, estrogen sulfatase (STS) and estrogen sulfotransferase, also play pivotal roles in intratumoral estrogen production.

Analysis for localization of steroid sulfatase in human tissues.

Human steroid sulfatase (STS) is an enzyme that hydrolyzes several sulfated steroids, such as estrone sulfate, dehydroepiandrosterone sulfate, and cholesterol sulfate, and results in the production of active substances. STS has been demonstrated in human breast cancer tissues and is considered to be involved in intratumoral estrogen production. It is very important to analyze the cellular distribution of STS with accuracy in human tissues in order to obtain a better understanding of the biological significance of STS.

Estrogen inhibits cell proliferation through in situ production in human thymoma.

Purpose: We showed previously estrogen receptor (ER) alpha as an independent prognostic marker in human thymoma. Estrogen sulfotransferase (EST), steroid sulfatase (STS), 17beta-hydroxysteroid dehydrogenase (17beta-HSD), and aromatase are considered to play important roles in hormone metabolism of estrogen-dependent tumors.

Experimental Design: We examined estrogen production using primary cultures of human thymoma epithelial cells (TEC), intratumoral estradiol (E(2)) concentrations, and status of these enzymes above using immunohistochemistry or semiquantitative reverse transcription-PCR.

Urocortin 1, urocortin 3/stresscopin, and corticotropin-releasing factor receptors in human adrenal and its disorders.

Context: Urocortin 1 (Ucn1) and urocortin 3 (Ucn3)/stresscopin are new members of the corticotropin-releasing factor (CRF) neuropeptide family. Ucn1 binds to both CRF type 1 (CRF1) and type 2 receptors (CRF2), whereas Ucn3 is a specific agonist for CRF2. Recently, direct involvement of the locally synthesized CRF family in adrenocortical function has been proposed.

Steroid sulfatase and estrogen sulfotransferase in human endometrial carcinoma.

Purpose: Intratumoral metabolism and synthesis of estrogens are considered to play important roles in the pathogenesis and/or development of human endometrial carcinoma. Steroid sulfatase hydrolyzes biologically inactive estrogen sulfates to active estrogens, whereas estrogen sulfotransferase sulfonates estrogens to estrogen sulfates. However, the status of steroid sulfatase and/or estrogen sulfotransferase in human endometrial carcinoma has not been examined.

Role of steroid sulfatase in local formation of estrogen in post-menopausal breast cancer patients.

More than two-thirds of breast cancers occur in post-menopausal women, and depend on the estrogens for their proliferation and survival. For the treatment of estrogen-dependent breast cancers, two major treatment options are now available. One is selective estrogen receptor modulator (SERM) such as Tamoxifen and another is aromatase inhibitor such as Anastrozole, Letrozole and Exemestane, which reduce local in situ formation of estrogens.

Steroid sulfatase and estrogen sulfotransferase in normal human tissue and breast carcinoma.

Steroid sulfatase (STS) hydrolyzes inactive estrone sulfate (E1-S) to estrone (E1), while estrogen sulfotransferase (EST; SULT 1E1 or STE gene) sulfonates estrogens to estrogen sulfates. They are considered to play important roles in the regulation of local estrogenic actions in various human tissues, however, their biological significance remains largely unknown. Therefore, we examined the expression of STS and EST in non-pathologic human tissues and breast carcinomas.

Steroid sulfatase and estrogen sulfotransferase in the atherosclerotic human aorta.

Various epidemiological studies have demonstrated a relatively low incidence of cardiovascular events in premenopausal women and its marked increment after menopause. In addition, estrogens have been postulated to exert direct anti-atherogenic effects via binding to estrogen receptors in vascular smooth muscle cells (VSMCs). However, not all postmenopausal women develop atherosclerosis despite decreased levels of serum estrogen.

Estrogen sulfotransferase and steroid sulfatase in human breast carcinoma.

Estrogen sulfotransferase (EST; SULT 1E1 or STE gene) sulfonates estrogens to inactive estrogen sulfates, whereas steroid sulfatase (STS) hydrolyzes estrone sulfate to estrone. Both EST and STS have been suggested to play important roles in regulating the in situ production of estrogens in human breast carcinoma tissues. However, the expression of EST has not been examined in breast carcinoma tissues, and the biological significance of EST and STS remains unknown.

Systemic distribution of steroid sulfatase and estrogen sulfotransferase in human adult and fetal tissues.

Estrogens play a key role in various target tissues. Enzymes involved in the biosynthesis and metabolism of these sex steroids also regulate estrogenic actions in these tissues. Estrone sulfate (E1S) is a major circulating plasma estrogen that is converted into the biologically active estrogen, estrone (E1), by steroid sulfatase (STS).