Characteristic Infrasound Events Associated with Sea-Ice Discharges in the Lützow-Holm Bay of Antarctica: April 2016

Infrasound waves detected in Antarctica contain information on the physical interaction among the surface environment at the margin of the continent and surrounding ocean. Time-space variation of source location for infrasound excitation during mid-April 2016 was investigated by using a combination of two arrays deployed along the coast of the Lützow-Holm Bay (LHB), East Antarctica. The infrasound array observations detected temporal variations in distance from the sources and propagation direction. A few tens of infrasound events were identified during 10 days of the period, and many of them located in the northward direction from the array stations were inside the LHB and offshore in the Southern Indian Ocean. Many of the events had predominant frequency content of few Hz, which were higher than microbaroms generated from the ocean. By comparing with MODIS satellite image at the same period, these sources were considered to be the ice-related phenomenon associated with the discharge of fast sea ice from the LHB

Locating earthquakes around Antarctica by using neural networks based on deep learning

The Tenth Symposium on Polar Science/Ordinary sessions: [OG] Polar Geosciences, Wed. 4 Dec. / Entrance Hall (1st floor), National Institute of Polar Researc

DNA複製因子MCM10の発現亢進による乳がん幹細胞維持機構の解析

金沢大学がん進展制御研究所本研究では、腫瘍の発生のみでなく治療後の再発の原因ともなり得るがん幹細胞と呼ばれる細胞集団において、特に重要な役割を担っていることが示唆されたMCM10という分子の役割を解明することを目的とする。これまでに我々はMCM10の発現を抑制することにより、がん細胞の集団中におけるがん幹細胞の割合を減少させられることを見出してきた。ここではその詳細なメカニズムを明らかにするとともに、実際の治療への応用を想定し、腫瘍形成後であってもMCM10を発現抑制することで十分な治療効果が得られるかについても検討を行なう。腫瘍は非常に不均一な細胞集団で構成されることが明らかになっており、その中には自己複製能と分化能を併せ持ち、腫瘍の発生のみでなく、治療後の再発の原因ともなるがん幹細胞 (Cancer stem-like cell; CSCs) と呼ばれる少数の細胞集団が存在することもわかってきた。CSCsを標的とした治療法を開発するため、申請者はこれまでにCSCsの性状解析を進めてきており、DNA複製に関与するminichromosome maintenance protein 10 (MCM10) の発現亢進がストレス環境下でのCSCsの生存に寄与することを見出してきた。siRNA等を用いたMCM10の発現抑制によってCSCsに優先的に細胞死を起こさせることができるというこれまでの実験結果に基づき、本研究ではMCM10の発現亢進がCSCsの生存に寄与するメカニズムを明らかにすることを目指した。申請者が最終年度に実施した解析の結果から、CSCsでは他のがん細胞と比較して遺伝子の転写活性が亢進しており、転写に関わる因子と複製に関わる因子の衝突がDNA上で高頻度で生じていることが明らかになった。CSCs内で発現亢進を受けたMCM10はそのような複製ストレスの生じやすい環境において、休眠状態の複製起点を高効率で活性化させることでCSCsの生存や増殖に寄与していることを示唆する結果も得られた。このような研究結果より、予後不良の原因となるCSCsを治療標的とするうえでMCM10をターゲットにすることの有効性が示されたと考えられる。研究課題/領域番号:19K23910, 研究期間(年度):2019-08-30 – 2020-03-31出典：「DNA複製因子MCM10の発現亢進による乳がん幹細胞維持機構の解析」研究成果報告書　課題番号19K23910（KAKEN：科学研究費助成事業データベース（国立情報学研究所）） （https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-19K23910/ ）を加工して作

Oncogenic fusion gene CD74-NRG1 confers cancer stem cell-like properties in lung cancer through a IGF2 autocrine/paracrine circuit

The CD74-Neuregulin1 (NRG1) fusion gene was recently identified as novel driver of invasive mucinous adenocarcinoma, a malignant form of lung cancer. However, the function of the CD74-NRG1 fusion gene in adenocarcinoma pathogenesis and the mechanisms by which it may impart protumorigenic characteristics to cancer stem cells (CSC) is still unclear. In this study, we found that the expression of the CD74-NRG1 fusion gene increased the population of lung cancer cells with CSC-like properties. CD74-NRG1 expression facilitated sphere formation not only of cancer cells, but also of nonmalignant lung epithelial cells. Using a limiting dilution assay in a xenograft model, we further show that the CD74-NRG1 fusion gene enhanced tumor initiation. Mechanistically, we found that CD74-NRG1 expression promoted the phosphorylation of ErbB2/3 and activated the PI3K/Akt/NF-κB signaling pathway. Furthermore, the expression of the secreted insulin-like growth factor 2 (IGF2) and phosphorylation of its receptor, IGF1R, were enhanced in an NF-κB-dependent manner in cells expressing CD74-NRG1. These findings suggest that CD74-NRG1-induced NF-κB activity promotes the IGF2 autocrine/paracrine circuit. Moreover, inhibition of ErbB2, PI3K, NF-κB, or IGF2 suppressed CD74-NRG1-induced tumor sphere formation. Therefore, our study provides a preclinical rationale for developing treatment approaches based on these identified pathways to suppress CSC properties that promote tumor progression and recurrence. © 2016 American Association for Cancer Research

Drug resistance mechanisms of cancer stem-like cells and their therapeutic potential as drug targets

Despite of recent advances in cancer research and development of new anti-cancer drugs, tumor patients’ prognoses have not yet been improved well enough. Treatment failure of tumors is highly attributed to the drug resistance of a small population of cancer cell known as cancer stem-like cells (CSCs). CSCs also have the self-renewal activity and differentiation potency, conferring strong tumorigenicity on them. Therefore, development of CSC targeting therapy is urgently needed in order to overcome possible recurrence and metastasis by them after therapy. CSCs show some characteristic features that are not observed in other differentiated cancer cells, which give them higher resistance against conventional chemotherapy or radiotherapy. Targeting such specific features could be useful for CSC eradication. This review will summarize the recent advances in the study of CSC characteristics along with the promising therapeutic strategies targeting them

Patient-Derived Xenograft Models of Breast Cancer and Their Application

Recently, patient-derived xenograft (PDX) models of many types of tumors including breast cancer have emerged as a powerful tool for predicting drug efficacy and for understanding tumor characteristics. PDXs are established by the direct transfer of human tumors into highly immunodeficient mice and then maintained by passaging from mouse to mouse. The ability of PDX models to maintain the original features of patient tumors and to reflect drug sensitivity has greatly improved both basic and clinical study outcomes. However, current PDX models cannot completely predict drug efficacy because they do not recapitulate the tumor microenvironment of origin, a failure which puts emphasis on the necessity for the development of the next generation PDX models. In this article, we summarize the advantages and limitations of current PDX models and discuss the future directions of this field

Finding Similarity and Comparability from Merged Hetero Data of the Semantic Web by Using Graph Pattern Matching

We propose a method to find similarity and compared points from merged hetero data of the Semantic Web using graph pattern matching. A query pattern based on simple keyword is automatically created by analyzing the frequent occurrence of patterns of data structures and by using individual user context. Therefore, this query allows users to extract not only a subgraph that includes the keyword but also a cluster of characteristic data related to the keyword or user profile and preference. We call the proposed method context structure matching (CSM). We have been trying to apply CSM to a large amount of o#ce data