Survivin: A novel marker and potential therapeutic target for human angiosarcoma.
Survivin: A novel marker and potential therapeutic target for human angiosarcoma.
复制标题
DOI：
10.1111/cas.13379
复制
发表时间：
2017-11
期刊：
影响因子：
5.7
通讯作者：
Arakawa H
中科院分区：
文献类型：
--
作者：
Tsuneki M;Kinjo T;Mori T;Yoshida A;Kuyama K;Ohira A;Miyagi T;Takahashi K;Kawai A;Chuman H;Yamazaki N;Masuzawa M;Arakawa H
人类血管肉瘤是一种罕见的恶性血管肿瘤，临床预后极差，通常发生于头颈部皮肤。然而，对血管肉瘤的分子发病机制和有用的免疫组化标记物知之甚少。为了研究血管肉瘤进展的机制，我们收集了85例有临床记录的人血管肉瘤标本，并分析了ISO-HAS-B患者来源的血管肉瘤细胞。对照组为血管瘤54例，化脓性肉芽肿34例。值得注意的是，与我们最近关于Hippo通路失活后Survivin表达参与小鼠血管内皮瘤细胞和人类婴儿血管瘤的肿瘤增殖的观察结果一致，在所有血管肉瘤病例中观察到细胞核Survivin表达，但在血管瘤和化脓性肉芽肿中未观察到，并且在90.3%的yes相关蛋白（雅普）阳性血管肉瘤病例中Hippo通路失活。然而，生存素表达模式和雅普定位（Hippo通路激活模式）与生存无关。此外，我们证实了生存素小干扰RNA（siRNA）转染和YM 155（一种抗生存素药物）在持续表达生存素的ISO-HAS-B细胞中引起了细胞核生存素表达和细胞增殖的降低。总之，这些研究结果支持生存素作为人类血管肉瘤细胞增殖的良好标志物和关键调节因子的重要性，以及YM 155作为潜在治疗剂的重要性。
Human angiosarcoma is a rare malignant vascular tumor associated with extremely poor clinical outcome and generally arising in skin of the head and neck region. However, little is known about the molecular pathogeneses and useful immunohistochemical markers of angiosarcoma. To investigate the mechanisms of angiosarcoma progression, we collected 85 cases of human angiosarcoma specimens with clinical records and analyzed ISO‐HAS‐B patient‐derived angiosarcoma cells. As control subjects, 54 cases of hemangioma and 34 of pyogenic granuloma were collected. Remarkably, consistent with our recent observations regarding the involvement of survivin expression following Hippo pathway inactivation in the neoplastic proliferation of murine hemangioendothelioma cells and human infantile hemangioma, nuclear survivin expression was observed in all cases of angiosarcoma but not in hemangiomas and pyogenic granulomas, and the Hippo pathway was inactivated in 90.3% of yes‐associated protein (YAP) ‐positive angiosarcoma cases. However, survivin expression modes and YAP localization (Hippo pathway activation modes) were not correlated with survival. In addition, we confirmed that survivin small interference RNA (siRNA) transfection and YM155, an anti‐survivin drug, elicited decreased nuclear survivin expression and cell proliferation in ISO‐HAS‐B cells which expressed survivin consistently. Conclusively, these findings support the importance of survivin as a good marker and critical regulator of cellular proliferation for human angiosarcoma and YM155 as a potential therapeutic agent.
登录
查看更多内容
第2阶段，棕褐色溴化物（YM155）的多中心，开放标签研究，以及III期（无法切除）或IV期黑色素瘤的患者中的多西烷。
影响因子：
4
作者：
Kudchadkar, Ragini;Ernst, Scott;Chmielowski, Bartosz;Redman, Bruce G.;Steinberg, Joyce;Keating, Anne;Jie, Fei;Chen, Caroline;Gonzalez, Rene;Weber, Jeffrey
通讯作者：
Weber, Jeffrey
影响因子：
5.6
作者：
Deyrup, Andrea T.;McKenney, Jesse K.;Weiss, Sharon W.
通讯作者：
Weiss, Sharon W.
影响因子：
3.6
作者：
Miura, H;Inui, S;Yoshikawa, K
通讯作者：
Yoshikawa, K
影响因子：
30.8
作者：
Behjati, Sam;Tarpey, Patrick S.;Sheldon, Helen;Martincorena, Inigo;Van Loo, Peter;Gundem, Gunes;Wedge, David C.;Ramakrishna, Manasa;Cooke, Susanna L.;Pillay, Nischalan;Vollan, Hans Kristian M.;Papaemmanuil, Elli;Koss, Hans;Bunney, Tom D.;Hardy, Claire;Joseph, Olivia R.;Martin, Sancha;Mudie, Laura;Butler, Adam;Teague, Jon W.;Patil, Meena;Steers, Graham;Cao, Yu;Gumbs, Curtis;Ingram, Davis;Lazar, Alexander J.;Little, Latasha;Mahadeshwar, Harshad;Protopopov, Alexei;Al Sannaa, Ghadah A.;Seth, Sahil;Song, Xingzhi;Tang, Jiabin;Zhang, Jianhua;Ravi, Vinod;Torres, Keila E.;Khatri, Bhavisha;Halai, Dina;Roxanis, Ioannis;Baumhoer, Daniel;Tirabosco, Roberto;Amary, M. Fernanda;Boshoff, Chris;McDermott, Ultan;Katan, Matilda;Stratton, Michael R.;Futreal, P. Andrew;Flanagan, Adrienne M.;Harris, Adrian;Campbell, Peter J.
通讯作者：
Campbell, Peter J.
影响因子：
7.5
作者：
Mentzel, T.;Schildhaus, H. U.;Kutzner, H.
通讯作者：
Kutzner, H.