Kei Kawana

Consensus statement from 17 relevant Japanese academic societies on the promotion of the human papillomavirus vaccine

http://dx.doi.org/10.1016/j.vaccine.2017.03.015 0264-410X/ 2017 Elsevier Ltd. All rights reserved. ⇑ Corresponding author. E-mail address: kkawana-tky@umin.org (K. Kawana). 1 The Japanese Society for Vaccinology, The Japanese Association for Infectious Diseases, The Japanese Society of Child Health, Japan Society of Obstetrics and Gynecology, Japan Pediatric Society, Japan Pediatric Association, Japan Society for Well-being of Nursery-schoolers, The Japanese Respiratory Society, Japanese Society of Travel and Health, The Oto-Rhino-Laryngological Society of Japan, Japan Primary Care Association, Japanese Society for Infection Prevention and Control, The Japanese Society for Virology, Japanese Society for Bacteriology, Japanese Society of Clinical Virology, Japan Association of Obstetricians and Gynecologists, and Japan Society of Gynecologic Oncology (Associate society). Satoshi Iwata , Kenji Okada , Kei Kawana c,⇑, on behalf of the Expert Council on Promotion of Vaccination

Kaempferol, a natural dietary flavonoid, suppresses 17β‑estradiol‑induced survivin expression and causes apoptotic cell death in endometrial cancer

Endometrioid endometrial carcinoma, commonly known as type 1 endometrial cancer, accounts for >80% of endometrial carcinomas and is dependent on estrogen. We recently reported on the prognostic significance of the BIRC5 survivin gene in endometrial cancer. Estradiol induces survivin expression in estrogen receptor-positive, but not in estrogen receptor-negative, cancer cells. Kaempferol, a bioflavonoid, reportedly inhibits estrogen receptor-α (ERα) in hormone receptor-positive breast cancer cells. However, whether kaempferol-mediated inhibition of ERα suppresses survivin and induces cell death in endometrial cancer remains unclarified. The present study evaluated the antitumor effects of kaempferol on endometrial cancer cells. Cell viability assays, flow cytometry analysis, western blotting and annexin V analyses were used to analyze the antitumor effects of kaempferol. The results demonstrated that kaempferol successfully suppressed the viability of two ER-positive endometrial cancer cell lines, with IC50 values of 83 and 65 µM. In addition, kaempferol induced sub-G1 cell accumulation and apoptotic cell death (P<0.01) in a dose-dependent manner. Treatment of cells with estradiol significantly induced co-expression of nuclear ERα and survivin proteins (P<0.001). Further evaluation revealed that kaempferol causes apoptotic cell death largely by suppressing ERα, survivin and Bcl-2 protein. Therefore, the results of the present study suggested that targeting ERα and survivin with kaempferol may be a novel therapeutic option against endometrial carcinoma.

Intraperitoneal neutrophils activated by KRAS-induced ovarian cancer exert antitumor effects by modulating adaptive immunity

Increased neutrophil counts are a hallmark of a poor prognosis for cancer. We previously reported that KRAS promoted tumorigenesis and increased neutrophil counts in a mouse peritoneal cancer model. In the current study, we evaluated the role of increased neutrophils in cancer progression, as well as their influence on the intraperitoneal microenvironment. A mouse peritoneal cancer model was established using the KRAS-transduced mouse ovarian cancer cell line, ID8-KRAS. Neutrophil function was assessed by neutrophil depletion in ID8-KRAS mice. Neutrophil depletion markedly accelerated tumor formation; this was accompanied by an increase in interleukin-6 concentrations in ascites. Neutrophil depletion significantly decreased the amount of local and systemic CD8+ T cells, while increasing the amount of local CD4+ T cells, accompanied by an increased amount of monocytic myeloid-derived suppressor cells (M-MDSCs) and regulatory T cells (Tregs) (P<0.05). The roles of peritoneal neutrophils (PENs) in CD8+ T cell activation were assessed in vitro. PENs of ID8-KRAS mice had a strong potential to enhance T cell proliferation with a higher expression of the T cell costimulatory molecules OX40 ligand (OX40L) and 4-1BB ligand (4-1BBL), as compared with peripheral blood neutrophils (PBNs). These findings suggest that neutrophils recruited into the KRAS-induced tumor microenvironment (TME) have antitumor properties with the potential to modulate the numbers of M-MDSCs and Tregs and activate CD8+ T cells through T cell costimulatory molecules.

Tokishakuyakusan, a traditional Japanese medicine (Kampo) mitigates iNKT cell-mediated pregnancy loss in mice

Tokishakuyakusan (TSS) is a traditional herbal medicine that has been used empirically to prevent recurrent pregnancy loss. Its mode of action remains unclear. With their potent capacity to produce cytokines, invariant natural killer (iNKT) cells are involved in the control of fetomaternal immunity in early gestation. This study aimed to clarify the effect of TSS on iNKT cell activities in a well‐studied murine miscarriage model.

Characterization of human decidual mast cells and establishment of a culture system

BACKGROUND Although rodent decidual mast cells (MCs) reportedly play an important role in implantation and placenta formation, the characterization of human decidual MCs has been not well clarified. The aims of this study were to investigate the distribution and characteristics of MCs in human decidua and to establish a culture system for decidua-derived MCs. METHODS Decidual tissues were obtained from patients who underwent a legal elective abortion (6th week to 9th week of pregnancy), and decidual MCs were enzymatically dispersed. Cultured decidua-derived MCs were generated by culturing decidual cells with stem cell factor. An ultrastructural analysis of primary decidual MCs and cultured decidua-derived MCs was performed using a transmission electron microscope. Receptor and protease expression was analyzed using FACS. Histamine released from MCs was measured using enzyme immune assays. RESULTS A larger proportion of tryptase positive(+) MCs in decidua was present on the maternal side. Both enzymatically dispersed decidual MCs and cultured decidua-derived MCs showed an FcεRIα+Kit+tryptase+chymase+ phenotype. Their granules contenting particles exhibited variable amounts of electron-lucent space separating electron-dense particles. Both enzymatically dispersed decidual MCs and cultured decidua-derived MCs released comparable amounts of histamine following FcεRI aggregation. CONCLUSIONS The isolation method for MCs from decidua during early pregnancy and the culture system for decidua-derived MCs may enable the roles of decidual MC during pregnancy to be explored.

Labor prediction based on the expression patterns of multiple genes related to cervical maturation in human term pregnancy

This study explored the possibility of evaluating cervical maturation using swabbed cervical cell samples at term pregnancy, and aimed to develop a novel approach to predict labor onset.