マトリックス メタロプロテアーゼ 7 ワ SMAD4 ガ ケッソンシタ チョウカン ノ センガン ニ オイテ シュヨウ ケイセイ ニワ ヒツヨウ ダガ シンジュン ヤ カンシツ ゾウセイ ニワ ヒッス ノ ヨウソ デワ ナイ

京都大学0048新制・課程博士博士(医学)甲第14477号医博第3322号新制||医||973(附属図書館)UT51-2009-D189京都大学大学院医学研究科生理系専攻(主査)教授 野田 亮, 教授 藤田 潤, 教授 千葉 勉学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDA

Id2 deletion attenuates Apc-deficient ileal tumor formation

The expression level of inhibitor of DNA binding 2 (Id2) is increased in colorectal carcinomas and is positively correlated with poor prognosis. However, the functional significance of Id2 in intestinal tumorigenesis has not been fully defined using genetic approaches. Here, we show that Id2 promotes ileal tumor initiation in Apc-deficient mice. Expression of Id2 was stimulated by Wnt signaling through the enhancer region of the Id2 promoter at the early stage of tumorigenesis in Apc+/Δ716 (ApcΔ716) mice. Genetic depletion of Id2 in ApcΔ716 mice caused ∼80% reduction in the number of ileal polyps, but had little effect on tumor size. Notably, the lack of Id2 increased the number of apoptotic cells in the normal crypt epithelium of the mice. Furthermore, DNA microarray analysis revealed that the expression level of Max dimerization protein 1 (Mxd1), known as a c-Myc antagonist, was specifically increased by Id2 deletion in the ileal intestinal epithelium of ApcΔ716 mice. In contrast, the protein level of c-Myc, but not the mRNA level, was decreased by loss of Id2 in these mice. These results indicate that loss of Id2 inhibits tumor initiation by up-regulation of Mxd1 and down-regulation of c-Myc in ApcΔ716 mice

Acute leukemias in pregnant women: Results of a retrospective study at a local tertiary‐care hospital in Japan

Abstract Leukemia may rarely develop in a woman during pregnancy, posing clinical challenges to the patient, fetus, family, and medical staff managing malignancy and pregnancy. We retrospectively analyzed cases of pregnancy‐associated leukemia consecutively diagnosed and treated at a local tertiary‐care hospital in Nagano, Japan, over the past 20 years. Five cases were identified among 377,000 pregnancies in the area (one in every 75,000 pregnancies), all involving acute leukemia (three acute myelogenous leukemia [AML] and two acute lymphoblastic leukemia [ALL]). The cases were diagnosed in the first trimester (n = 1), second trimester (n = 3), or third trimester (n = 1). There were no apparent pregnancy‐associated delays in diagnosing and treating the cases. Three patients underwent induction chemotherapy during pregnancy, two of whom eventually delivered healthy babies. One of the five patients chose abortion before chemotherapy initiation. Two cases showing high‐risk features at the diagnosis (AML with an FLT3‐ITD mutation [n = 1] and relapsed ALL [n = 1]) eventually died despite consolidative allogeneic hematopoietic stem cell transplantation. Our results suggested that patients with pregnancy‐associated acute leukemia can be treated similarly to nonpregnant patients, although pregnancy imposes particular clinical challenges that should be resolved with multidisciplinary care