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通过抑制 P 糖蛋白介导的药物耐受持久细胞中有毒脂质过氧化副产物的清除，有效靶向治疗乳腺癌
Therapy resistance has long been considered to occur through the selection of pre-existing clones equipped to survive and quickly regrow, or through the acquisition of mutations during chemotherapy. Here we show that following in vitro treatment by chemotherapy, epithelial breast cancer cells adopt a transient drug tolerant phenotype characterized by cell cycle arrest, epithelial-to-mesenchymal transition (EMT) and the reversible upregulation of the multidrug resistance (MDR) efflux transporter P-glycoprotein (P-gp). The drug tolerant persister (DTP) state is reversible, as cells eventually resume proliferation, giving rise to a cell population resembling the initial, drug-naïve cell lines. However, recovery after doxorubicin treatment is almost completely eliminated when DTP cells are cultured in the presence of the P-gp inhibitor Tariquidar. Mechanistically, P-gp contributes to the survival of DTP cells by removing reactive oxygen species-induced lipid peroxidation products resulting from doxorubicin exposure. In vivo, prolonged administration of Tariquidar during doxorubicin treatment holidays resulted in a significant increase of the overall survival of Brca1 − / − ;p53 − / − mammary tumor bearing mice. These results indicate that prolonged administration of a P-gp inhibitor during drug holidays would likely benefit patients without the risk of aggravated side effects related to the concomitantly adminis tered toxic chemotherapy. Effective targeting of DTPs through the inhibition of P-glycoprotein may result in a paradigm shift, changing the focus from countering drug resistance mechanisms to preventing or delaying therapy resistance.
4A-302.监护计划和命令。
母亲节 _______ _______ 从 _________ 到 _________ 父亲节 _______ _______ 从 _________ 到 _________ 儿童生日 _______ _______ 从 _________ 到 _________ 万圣节 _______ _______ 从 _________ 到 _________ 感恩节假期 _______ _______ 从 _________ 到 _________ 冬季宗教节日 _______ _______ 从 _________ 到 _________ 第一个 1/2 个寒假 _______ _______ 从 _________ 到 _________ 第二个 1/2 个寒假 _______ _______ 从 _________ 到 _________ 春假 _______ _______ 从_________ 至 _________ 7 月 4 日 _______ _______ 从 _________ 至 _________ 其他宗教节日 _______ _______ 从 _________ 至 _________ 其他：_______ _______ 从 _________ 至 _________
ASU 101
出勤和参加课堂活动是学习过程的重要组成部分，预计学生将定期上课。但是，某些缺席是不可避免的。在（1）大学批准的事件[ACD 304-02]的情况下，将不对等级的罚款。 （2）宗教假期[ACD 304-04;可以在此处找到列表https://eoss.asu.edu/cora/holidays]; （3）根据[SSM 201-18]在工作期间进行的工作； （4）与卫生专业人员有关的疾病，隔离或自我隔离。预计大学批准的活动，宗教假期或结婚活动应至少在预期缺席前10天通过电子邮件传达给教练。缺勤与疾病相关的疾病，隔离或自我隔离应由卫生专业人员记录，并通过电子邮件尽快与教练通讯。
专利教师官方杂志专利局
15。diwali（Deepavali）11月4日，星期四16.Guru Nanak的生日11月19日，星期五。圣诞节12月25日星期六注意：中央政府组织，其中包括工业，商业和培训机构（即除了做秘书处的工作外，还将在一年中观察17个假期，其中第3个（共和国日，独立日和圣雄甘地的生日）将是强制性的。剩余的假期/场合可以由此类机构/组织本身逐年确定。在确定特定部门/机构/组织是否是工业，商业或贸易组织（即除了从事秘书处工作的那些人以外，新德里内政部/内政部可以做出决定。穆斯林节日的假期日期可能会在看到月球并决定被州政府采取的决定时改变。
