Effects of FGF2 on the leukemia microenvironment in the bone marrow

FGF2对骨髓白血病微环境的影响

• 批准号: 23591382
• 负责人: NAKAYAMA Takayuki
• 金额: $ 3.33万
• 依托单位: Aichi Medical University (2012-2013)Nagoya University (2011)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23591382/
• 关键词: 血液腫瘍学; 血液悪性腫瘍幹細胞; ニッチェ; 血液学; 腫瘍微小環境; ケモカイン; 白血病ニッチェ

We examined effects of FGF2 on interaction between leukemia cells and its microenvironment. Significantly fewer AML cells were recovered from cocultures with murine stromal monolayers treated with FGF2 than from control. FGF2 also facilitate the sensitivity of CML cells toward imatinib in the coculture. Accordingly, AML cells in cell cycle quiescent are less in FGF2-treated monolayers than control. We next treated human AML mouse model with Ara-C in combination w/wo FGF2. BM sections from FGF2-treated mice displayed thickened bone trabeculae and an increased number of leukemia cells compared to control. FGF2 did not help leukemia cells survive from Ara-C in the spleen. These observations suggest that the endosteal region consisting of osteoblasts is important for leukemia cells to survive from chemotherapy, and that FGF2 favors leukemia cell in the BM via promoting osteoblast functions.

我们研究了 FGF2 对白血病细胞与其微环境之间相互作用的影响。从用 FGF2 处理的鼠基质单层共培养物中回收的 AML 细胞明显少于对照细胞。 FGF2 还促进共培养中 CML 细胞对伊马替尼的敏感性。因此，FGF2处理的单层细胞中处于细胞周期静止状态的AML细胞比对照少。接下来，我们用 Ara-C 联合 FGF2 治疗人类 AML 小鼠模型。与对照组相比，FGF2 治疗小鼠的骨髓切片显示骨小梁增厚，白血病细胞数量增加。 FGF2 不能帮助白血病细胞从脾脏中的 Ara-C 中存活下来。这些观察结果表明，由成骨细胞组成的骨内膜区域对于白血病细胞从化疗中存活下来非常重要，并且FGF2通过促进成骨细胞功能而有利于BM中的白血病细胞。

项目成果

Successful fertility management of a patient with factor V deficiency: planned transfusion of fresh frozen plasma under infertility treatment

因子 V 缺乏症患者的成功生育管理：在不孕症治疗中计划输注新鲜冰冻血浆

• DOI: 10.1016/j.fertnstert.2011.01.011
• 发表时间: 2011
• 期刊: Fertil Steril
• 影响因子: 6.7
• 作者: Iwase A;Matsushita T
• 通讯作者: Matsushita T

Pitavastatin-induced angiogenesis and arteriogenesis is mediated by Notch1 in a murine hindlimb ischemia model without induction of VEGF.

• DOI: 10.1038/labinvest.2011.5
• 发表时间: 2011-05
• 期刊: Laboratory investigation; a journal of technical methods and pathology

Recovery of flow-mediated vasodilatation after repetitive measurements is involved in early vascular impairment: comparison with indices of vascular tone.

• DOI: 10.1371/journal.pone.0083977
• 发表时间: 2014
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Inaba H;Takeshita K;Uchida Y;Hayashi M;Okumura T;Hirashiki A;Yoshikawa D;Ishii H;Yamamoto K;Nakayama T;Hirayama M;Matsumoto H;Matsushita T;Murohara T
• 通讯作者: Murohara T

Stress augments insulin resistance and prothrombotic state: role of visceral adipose-derived monocyte chemoattractant protein-1.

• DOI: 10.2337/db11-0828
• 发表时间: 2012-06
• 期刊: Diabetes
• 影响因子: 7.7
• 作者: Uchida Y;Takeshita K;Yamamoto K;Kikuchi R;Nakayama T;Nomura M;Cheng XW;Egashira K;Matsushita T;Nakamura H;Murohara T
• 通讯作者: Murohara T

造血支持を目的としたヒト脂肪組織由来間葉系幹細胞の有効性、安全性の検討

检查人类脂肪组织来源的间充质干细胞用于支持造血的功效和安全性

• 发表时间: 2011
• 作者: 中山享之;中尾典彦;直江知樹
• 通讯作者: 直江知樹