Drug Repositioning for Gynecologic Tumors: A New Therapeutic Strategy for Cancer

The goals of drug repositioning are to find a new pharmacological effect of a drug for which human safety and pharmacokinetics are established and to expand the therapeutic range of the drug to another disease. Such drug discovery can be performed at low cost and in the short term based on the results of previous clinical trials. New drugs for gynecologic tumors may be found by drug repositioning. For example, PPAR ligands may be effective against ovarian cancer, since PPAR activation eliminates COX-2 expression, arrests the cell cycle, and induces apoptosis. Metformin, an antidiabetic drug, is effective for endometrial cancer through inhibition of the PI3K-Akt-mTOR pathway by activating LKB1-AMPK and reduction of insulin and insulin-like growth factor-1 due to AMPK activation. COX-2 inhibitors for cervical cancer may also be examples of drug repositioning. PGE2 is induced in the arachidonate cascade by COX-2. PGE2 maintains high expression of COX-2 and induces angiogenic factors including VEGF and bFGF, causing carcinogenesis. COX-2 inhibitors suppress these actions and inhibit carcinogenesis. Combination therapy using drugs found by drug repositioning and current anticancer drugs may increase efficacy and reduce adverse drug reactions. Thus, drug repositioning may become a key approach for gynecologic cancer in drug discovery

MicroRNAs in endometrial cancer

Endometrial cancer is a common malignant gynecological tumor, but there are few biomarkers that are useful for early and accurate diagnosis and few treatments other than surgery. However, use of microRNAs (miRNAs) that induces gene downregulation in cells may permit effective and minimally invasive diagnosis and treatment. In endometrial cancer cells, expression levels of miRNAs including miR-185, miR-210 and miR-423 are upregulated and those of miR-let7e, miR-30c and miR-221 are downregulated compared to normal tissues, and these miRNAs are involved in carcinogenesis, invasion and metastasis. miRNAs with expression changes such as miR-181b, miR-324-3p and miR-518b may be used as prognostic biomarkers and transfection of miR-152 may inhibit cancer growth. However, most current studies of miRNAs are at a basic level and further work is needed to establish clinical applications targeting miRNAs

Interdisciplinary Class on the Climate Environment around the Japan Islands in Association with the Seasonal Feeling (with Attention to the Transition Stage from Autumn to Winter)

The complicated seasonal variations are found in East Asia influenced by the Asian monsoon, resulting in the variety of “seasonal feeling”. For example, although the air temperature around the Japan Islands is still rather higher from November to early December than in the midwinter, the wintertime weather pattern often appears then due to the development of the Siberian high. In the Hokuriku District, the Japan Sea side of the central Japan, the shallow convective rainfall called the “Shi-gu-re” frequently occurs associated with the air mass transformation process over the Japan Sea in the cold air outbreak situation from the continent. It is also well known that the “Shi-gu-re” is often used for expression of the “seasonal feeling” in the Japanese classical literature. Thus the present study tried to develop an interdisciplinary class on the climate environment around the Japan Islands in association with the “seasonal feeling”, with attention to the transition stage from autumn to winter. The present paper will discuss on the joint activity of meteorology with the Japanese classical literature, the music and the art, for the class at the Faculty of Education, Okayama University, and that at the Okayama-Ichinomiya High School

Study on the Teaching Strategy of an Junior High School and Improving the Program for Training Students to be Teachers of University (2) : In the Case of Music, Health and Physical Education, Art, Technology and Home Economics (Field of Technology)

　本研究は，教科内容構成の考え方に基づいて中学校の授業づくりのあり方を検討するとともに，それをふまえることで大学の教員養成プログラムの授業が具体的にどのように改善されるかを明らかにしようとしたものである。教科内容構成とは，教員養成において従来から課題とされてきた教科の内容に関わる知識・技能と教科の指導法に関わる知識・技能の分離という問題を克服するために提案されたものである。教科内容構成は，教科の内容と指導法に関わる知識・技能を統合し，それらを応用して，教師が自ら「どのような内容をどのように教えるべきか」を考え，授業づくりに取り組むことができるようになるための考え方を示すものであり，本研究では教員養成プログラムにおける具体的な授業プランを提示してそれを明らかにしていく。本稿では，特に，中学校の音楽科，保健体育科，美術科，技術・家庭科（技術分野）を事例として論じていくことにしたい

第2回「卒業生の保健師の集い」をふりかえって

第2回「卒業生の保健師の集い」を、第1部「健康日本21と保健計画」の講演と第2部では3つのテーマ(家族援助、個別健康教育、精神保健相談)を設定しての分科会形式で実施した。分科会32名の参加者の声は「他の市区町村の活動内容を知り、自分の活動と比較検討して今後の参考となった、と同時に明日への活力になった」というものが最も多く、情報交換のニーズの高さや交流の場の必要性が確認された

SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion

Abstract: The B.1.617.2 (Delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha)1. In vitro, B.1.617.2 is sixfold less sensitive to serum neutralizing antibodies from recovered individuals, and eightfold less sensitive to vaccine-elicited antibodies, compared with wild-type Wuhan-1 bearing D614G. Serum neutralizing titres against B.1.617.2 were lower in ChAdOx1 vaccinees than in BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies to the receptor-binding domain and the amino-terminal domain. B.1.617.2 demonstrated higher replication efficiency than B.1.1.7 in both airway organoid and human airway epithelial systems, associated with B.1.617.2 spike being in a predominantly cleaved state compared with B.1.1.7 spike. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralizing antibody, compared with that of wild-type spike. We also observed that B.1.617.2 had higher replication and spike-mediated entry than B.1.617.1, potentially explaining the B.1.617.2 dominance. In an analysis of more than 130 SARS-CoV-2-infected health care workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx1 vaccine effectiveness against B.1.617.2 relative to non-B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune-evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era

Enhanced fusogenicity and pathogenicity of SARS-CoV-2 Delta P681R mutation

SARS-CoV-2デルタ株に特徴的なP681R変異は ウイルスの病原性を増大させる. 京都大学プレスリリース. 2021-11-26.During the current SARS-CoV-2 pandemic, a variety of mutations have accumulated in the viral genome, and currently, four variants of concern (VOCs) are considered potentially hazardous to human society1. The recently emerged B.1.617.2/Delta VOC is closely associated with the COVID-19 surge that occurred in India in the spring of 20212. However, its virological properties remain unclear. Here, we show that the B.1.617.2/Delta variant is highly fusogenic and notably more pathogenic than prototypic SARS-CoV-2 in infected hamsters. The P681R mutation in the spike protein, which is highly conserved in this lineage, facilitates spike protein cleavage and enhances viral fusogenicity. Moreover, we demonstrate that the P681R-bearing virus exhibits higher pathogenicity than its parental virus. Our data suggest that the P681R mutation is a hallmark of the virological phenotype of the B.1.617.2/Delta variant and is associated with enhanced pathogenicity