CN115769077A - 用于治疗癌症的方法和组合物 - Google Patents
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| US20090047675A1 (en) * | 2007-05-01 | 2009-02-19 | Dana-Farber Cancer Institute, Inc. | Compositions and methods for indentifying transforming and tumor suppressor genes |
| US20160008361A1 (en) * | 2012-11-28 | 2016-01-14 | Merck Sharp & Dohme Corp. | Compositions and methods for treating cancer |
| WO2016210134A1 (en) * | 2015-06-23 | 2016-12-29 | Case Western Reserve University | Compositions and methods for treating cancer |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090047675A1 (en) * | 2007-05-01 | 2009-02-19 | Dana-Farber Cancer Institute, Inc. | Compositions and methods for indentifying transforming and tumor suppressor genes |
| US20160008361A1 (en) * | 2012-11-28 | 2016-01-14 | Merck Sharp & Dohme Corp. | Compositions and methods for treating cancer |
| WO2016210134A1 (en) * | 2015-06-23 | 2016-12-29 | Case Western Reserve University | Compositions and methods for treating cancer |
Non-Patent Citations (3)
| Title |
|---|
| GODFREY GRECH等: "Deregulation of the protein phosphatase 2A, PP2A in cancer: complexity and therapeutic options", TUMOR BIOLOGY, vol. 37, 21 July 2016 (2016-07-21), pages 11691 - 11700, XP036084812, DOI: 10.1007/s13277-016-5145-4 * |
| QINGYI ZHANG等: "Overexpressed PKMYT1 promotes tumor progression and associates with poor survival in esophageal squamous cell carcinoma", CANCER MANAGEMENT AND RESEARCH, vol. 11, 19 August 2019 (2019-08-19), pages 7813 - 7824, XP055870434, DOI: 10.2147/CMAR.S214243 * |
| 潘耀振: "POU5F1B通过激活AKT,miR-660通过抑制PPP2R2A促进肝细胞癌的增殖", 中国优秀博士学位论文全文数据库, no. 01, 15 January 2019 (2019-01-15), pages 072 - 096 * |
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