发明授权
US09528982B2 Bad phosphorylation determines ovarian cancer chemo-sensitivity and patient survival
有权
不良磷酸化决定了卵巢癌的化学敏感性和患者生存
- 专利标题: Bad phosphorylation determines ovarian cancer chemo-sensitivity and patient survival
- 专利标题(中): 不良磷酸化决定了卵巢癌的化学敏感性和患者生存
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申请号: US14010003申请日: 2013-08-26
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公开(公告)号: US09528982B2公开(公告)日: 2016-12-27
- 发明人: Johnathan Lancaster , Douglas Marchion , Dung-Tsa Chen
- 申请人: H. Lee Moffitt Cancer Center and Research Institute, Inc.
- 申请人地址: US FL Tampa
- 专利权人: H. Lee Moffitt Cancer Center and Research Institute, Inc.
- 当前专利权人: H. Lee Moffitt Cancer Center and Research Institute, Inc.
- 当前专利权人地址: US FL Tampa
- 代理机构: Smith & Hopen, P.A.
- 代理商 Michele L. Lawson; Robert J. Varkonyi
- 主分类号: G01N33/574
- IPC分类号: G01N33/574 ; G01N33/50
摘要:
Despite initial sensitivity BAD-protein phosphorylation were evaluated in patient samples and cell lines as determinants of chemo-sensitivity and/or clinical outcome, and as therapeutic targets. Induced in-vitro OVCA cisplatin-resistance was associated with BAD-pathway expression. Expression of the pathway was also associated with resistance of 7 different cancers cell-types to 8 chemotherapeutic agents. Phosphorylation of the BAD-protein was associated with platinum-resistance in OVCA cells and primary OVCA specimens, and also overall patient survival. Targeted modulation of BAD-phosphorylation levels influenced cisplatin-sensitivity. A 47-gene BAD-pathway signature was associated in-vitro phospho-BAD levels and with survival of 838 patients with ovarian, breast, colon, and brain cancer. The survival advantage associated with both BAD-phosphorylation and also the BAD-pathway signature was independent of surgical cytoreductive status. The BAD apoptosis pathway influences human cancer chemo-sensitivity and overall survival. The pathway is useful as a biomarker of therapeutic response, patient survival, and therapeutic target.
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