Aberrant expression and mutations of TGF-β receptor type II gene in endometrial cancer

取得学位 : 博士（医学）, 学位授与番号 : 医博甲第1930号 , 学位授与年月日 : 平成20年3月22日, 学位授与大学 : 金沢大学, 主査教授 : 西條 淸史, 副査教授 : 並木 幹夫 , 源 利

生涯にわたる健康づくりを志向した、管理栄養士養成課程の学生の食物摂取状況の実態と評価

飽食時代といわれる現代の日本にあって、生活習慣病の増加や欠食、近年では若年者におけるダイエット志向の高まりなど、食に関わる問題が多数存在している。そのような状況の中、これらを改善していく指導者を目指し学習している管理栄養士養成課程の女子大学生において適切な食生活が営まれ、得た知識や技術が生かされているか食物摂取状況を調査し、平成12年度の国民栄養調査結果と比較し検討した。摂取した栄養素では鉄が不足していたが、その他についてはほぼ適正であった。食品群では砂糖類、菓子類、油脂類、その他の食品が望ましい摂取目標量を上回り、種実類、いも類、その他の野菜、きのこ類は目標量を下回った。国民栄養調査結果で低値であった海藻類については、対象女子大生では高値、乳類についてはほぼ適正であった。エネルギー充足率を中心に見た栄養素摂取の評価結果より、管理栄養士課程の学生、とりわけ高学年(4年生)では、4年間にわたる栄養士教育の中で学習した知識が生かされ、日常生活において自然に栄養バランスが良くなるように食品を選び、組み合わせていくといったように、学生の食事に対する考えが変容されることが示唆された

Concomitant activation of AKT with extracellular-regulated kinase 1/2 occurs independently of PTEN or PIK3CA mutations in endometrial cancer and may be associated with favorable prognosiss

がん進展制御研究所　Deregulated signaling via the phosphatidylinositol 3-kinase (PI3K) pathway is common in many types of cancer, but its clinicopathological significance in endometrial cancer remains unclear. In the present study, we examined the status of the PI3K signaling pathway, especially in relation to PTEN and PIK3CA status, in endometrioid-type endometrial cancer. The immunohistochemical analysis revealed a high level of phosphorylated (p)-AKT expression, which is a hallmark of activated PI3K signaling, in approximately 60% of endometrial cancers. There was no correlation between p-AKT expression and clinicopathological characteristics, such as International Federation of Gynecology and Obstetrics stage, tumor grade, and myometrial invasion. Unexpectedly, a high level of p-AKT expression occurred independently of the presence of PTEN or PIK3CA mutations. Furthermore, p-AKT expression did not correlate with the expression of potential downstream targets, including p-mTOR and p-FOXO1/3a. In turn, p-AKT expression was strongly associated with extracellular-regulated kinase 1/2 expression (P = 0.0031), which is representative of the activated RAS-MAP kinase pathway. Kaplan-Meier analysis suggested that low p-AKT expression was associated with low rates of relapse-free survival, although the difference was not statistically significant, indicating that AKT activation does not confer worse prognosis. The present study demonstrates the presence of complex signaling pathways that might mask the conventional tumorigenic PTEN-PI3K-AKT-mTOR pathway, and strongly suggests a close association between the extracellular-regulated kinase and PI3K pathways in this tumor type. © 2007 Japanese Cancer Association

Activation of ERK1/2 occurs independently of KRAS or BRAF status in endometrial cancer and is associated with favorable prognosis

がん進展制御研究所The extracellular-regulated kinase (ERK) signaling pathway plays important roles in regulating the malignant potential of cancer cells in vitro. However, the effect of ERK signaling on the prognosis of human tumors is not clearly understood. The present study examined the expression of phosphorylated ERK1/2 (p-ERK1/2) as a hallmark of ERK activation, in relation to KRAS and BRAF mutations, in 63 endometrial cancer specimens with endometrioid-subtype, in order to clarify the prognostic value of p-ERK1/2 expression. Immmunohistochemical analysis revealed that 40 tumors (63%) expressed p-ERK1/2, with varying levels of expression. Total ERK1/2 expression was also evaluated in a subset of tumors; most cases expressed ERK1/2 constitutively but no correlation was observed with p-ERK expression, indicating that p-ERK1/2 staining was not due to ERK overexpression but to hyperactivation of ERK1/2. There was no statistically significant correlation between p-ERK1/2 expression and clinicopathological features, including patient age, International Federation of Gynecology and Obstetrics stage, pathological grade, myometrial invasion and lymph node metastasis. Sequencing analysis indicated that 23% of patients had a mutation in exon 1 of KRAS, whereas none of the patients had a mutation in exons 11 or 15 of BRAF, which are reportedly hot spots for mutation in many tumor types. There was no significant correlation between KRAS or BRAF status and p-ERK1/2 expression. Unexpectedly, patients with low p-ERK1/2 expression had significantly lower relapse-free survival (P = 0.041) and overall survival (P = 0.020). Multivariate Cox regression analysis indicated that p-ERK1/2 expression was an independent prognostic indicator for overall survival (P = 0.047). These findings suggest that ERK activation occurs in a KRAS - and BRAF-independent manner in endometrial cancer, and is associated with favorable prognosis. © 2007 Japanese Cancer Association

Accuracy management survey of nucleic acid amplification tests using inactivated SARS-CoV-2 in Hiroshima Prefecture

At the beginning of 2020, the number of laboratories performing SARS-CoV-2 testing increased with the rapid expansion of COVID-19 in Hiroshima Prefecture. Thus, it is necessary to compare and verify the validity of the test results among local laboratories. In this study, we distributed the same standard samples to laboratories that performed COVID-19 testing using the nucleic acid amplification method and confirmed the accuracy of the tests. The SARS-CoV-2 strain distributed by the National Institute of Infectious Diseases (NIID), Japan, was used for testing. As measured by RT-qPCR, a specific amount of the virus was inactivated by ethanol and dried as specimens for distribution. This study included 27 tests performed at 15 laboratories conducting or planning to conduct nucleic acid amplification tests (RT-qPCR and LAMP methods) for SARSCoV-2. The detection limit of each test method was set at the value provided by the NIID. The accuracy of the tests was examined to determine whether they met the required accuracy criteria. SARS-CoV-2 genomic RNA was reliably detected in all 27 tests. The inactivated specimens used in this study were safe to distribute and could be used as positive controls for all methods.This study was supported by a grant from the Government-Academia Collaboration of Hiroshima Prefecture and by a research grant for COVID-19 from AMED, Japan under Grant Number 20he0622011h0001(to J. T.)

Synthesis of Trifunctional Poly(propylene glycol) with Acetal Linkages and Properties of Chemically Recyclable Crosslinked Polyurethanes Prepared Therefrom

The synthesis and characterization of chemically recyclable crosslin.ked polyurethanes were studied in this work. Acetal units were introduced into polypropylene glycol having three hydroxyl terminal groups (PPG) by the reaction of the hydroxy groups of PPG with 4-acetoxybutyl vinyl ether followed by conversion of the acetate groups into hydroxy groups. Crosslinked polyurethanes were prepared by the reaction of the acetal-containing polyols (PPG-acetal-OH) with tolylene diisocyanates (TDI) at 120 °C under vacuum. The obtained polyurethanes formed elastomeric films and exhibited good mechanical properties. The treatment of the polyurethane films with aqueous acid at room temperature caused smooth hydrolysis of their acetal units to give PPG as a degradation product

A Novel iRFP-Incorporated in vivo Murine Atherosclerosis Imaging System

By using near-infrared fluorescent protein (iRFP)-expressing hematopoietic cells, we established a novel, quantitative, in vivo, noninvasive atherosclerosis imaging system. This murine atherosclerosis imaging approach targets macrophages expressing iRFP in plaques. Low-density lipoprotein receptor-deficient (LDLR−/−) mice transplanted with beta-actin promoter-derived iRFP transgenic (TG) mouse bone marrow (BM) cells (iRFP → LDLR−/−) were used. Atherosclerosis was induced by a nonfluorescent 1.25% cholesterol diet (HCD). Atherosclerosis was compared among the three differently induced mouse groups. iRFP → LDLR−/− mice fed a normal diet (ND) and LDLR−/− mice transplanted with wild-type (WT) BM cells were used as controls. The in vivo imaging system (IVIS) detected an enhanced iRFP signal in the thoracic aorta of HCD-fed iRFP → LDLR−/− mice, whereas iRFP signals were not observed in the control mice. Time-course imaging showed a gradual increase in the signal area, which was correlated with atherosclerotic plaque progression. Oil red O (ORO) staining of aortas and histological analysis of plaques confirmed that the detected signal was strictly emitted from plaque-positive areas of the aorta. Our new murine atherosclerosis imaging system can noninvasively image atherosclerotic plaques in the aorta and generate longitudinal data, validating the ability of the system to monitor lesion progression

食塩摂取量と尿中食塩排泄量との関係 : 新カリキュラム体制における学生実験の新たな取り組み

栄養士法改正に伴う管理栄養士・栄養士養成の新カリキュラム体制における新科目『栄養学総論実験』の授業内容に本実験を取り上げ、食塩含量が異なる食事を摂ったときの尿中排泄食塩量を測定することによりヒトを対象としたナトリウムの体内環境恒常性の維持機構を学ぶと共に、摂取食塩量を推算する試みを行った。尿中食塩含量の測定には、汁物などの食品中の塩分を測定する塩分計を用いた簡易法とモール法による沈殿滴定法の両者で行い比較した。その結果、実験者の不慣れや塩分計がおおまかな表示であったこともあり多少の誤差が生じたが、簡易法は自分自身の尿を簡単に測定することができ、しかも学生全員が自ら実験を実施することができるため、特に精密さを要求されないような場合はこの方法を用いることは妥当であると考えられた。食事内容は各自の判断で食塩量を控えた食事または普通食(「減塩食」)と積極的に塩分を摂取する食事(「増塩食」)の2種類を設定したが、大多数の者がその増減に対応した排泄量を示したものの、「減塩食」摂取時の方が「増塩食」摂取時よりも食塩排泄量が多かった学生もいた。履修者が2年生ということもあって、食品に対する知識不足が伺えた。排泄量から摂取食塩量が推測されるため今後この授業を進めていく上で、普段の食事、即ち各自の味覚に沿った食事摂取を実験項目に加えたならば、日常の食塩摂取状態を知ることができ、現在の食生活を見直すきっかけになるものと思われた。尿中への食塩排泄に関しては、観察した期日内では食事時間による影響は見られず、また時間経過による何らかの傾向も認められなかった。しかし、尿量と食塩排泄量とは正の相関が見られ、過剰に摂取された食塩は多量の水の摂取により、共に排泄が促進されることが推察された

ジョシ ダイガクセイ ニオケル セッシュ エイヨウソ ノ ジュウソク ジョウキョウ

本学被服学科4年次(大学生)同短期大学家政学科被服コース2年次(短大生)に在籍する女子学生に平成7年・8年・9年・10年の5月に,生活活動状況・アルバイトおよびクラブ活動の有無・生活活動状況と同一日の食事状況などについて調査を行い,調査結果から生活活動指数およびエネルギーならびに各栄養素の充足状況を観察した。その結果,体位については全国平均値と比較して身長はやや高く,それに伴い体重もやや重かった。生活活動強度は学生の約7割以上が強度IとIIに該当した。栄養素量摂取状況は,年度別ではたんぱく質と脂質においては100%の充足率を示している割合が高く,その他はほとんど満たしていなかった。強度別では強度IとIIにおいてエネルギー,たんぱく質,脂質が,強度IIIで鉄,強度IVでカルシウムが他の強度に比べて充足率が高かったが,その他は低い値であった。個人的にも,全体的にもエネルギー,カルシウム,鉄の不足は顕著であった

Alteration of the immune environment in bone marrow from children with recurrent B cell precursor acute lymphoblastic leukemia

Due to the considerable success of cancer immunotherapy for leukemia, the tumor immune environment has become a focus of intense research; however, there are few reports on the dynamics of the tumor immune environment in leukemia. Here, we analyzed the tumor immune environment in pediatric B cell precursor acute lymphoblastic leukemia by analyzing serial bone marrow samples from nine patients with primary and recurrent disease by mass cytometry using 39 immunophenotype markers, and transcriptome analysis. High-dimensional single-cell mass cytometry analysis elucidated a dynamic shift of T cells from naïve to effector subsets, and clarified that, during relapse, the tumor immune environment comprised a T helper 1-polarized immune profile, together with an increased number of effector regulatory T cells. These results were confirmed in a validation cohort using conventional flow cytometry. Furthermore, RNA transcriptome analysis identified the upregulation of immune-related pathways in B cell precursor acute lymphoblastic leukemia cells during relapse, suggesting interaction with the surrounding environment. In conclusion, a tumor immune environment characterized by a T helper 1-polarized immune profile, with an increased number of effector regulatory T cells, could contribute to the pathophysiology of recurrent B cell precursor acute lymphoblastic leukemia. This information could contribute to the development of effective immunotherapeutic approaches against B cell precursor acute lymphoblastic leukemia relapse