排序方式: 共有30条查询结果,搜索用时 437 毫秒
21.
Eduard Jirkovský Olga Lenčová-Popelová Miloš Hroch Michaela Adamcová Yvona Mazurová Jaroslava Vávrová Stanislav Mičuda Tomáš Šimůnek Vladimír Geršl Martin Štěrba 《Toxicology》2013
Despite incomplete understanding to its mechanism of action, dexrazoxane (DEX) is still the only clearly effective cardioprotectant against chronic anthracycline (ANT) cardiotoxicity. However, its clinical use is currently restricted to patients exceeding significant ANT cumulative dose (300 mg/m2), although each ANT cycle may induce certain potentially irreversible myocardial damage. Therefore, the aim of this study was to compare early and delayed DEX intervention against chronic ANT cardiotoxicity and study the molecular events involved. The cardiotoxicity was induced in rabbits with daunorubicin (DAU; 3 mg/kg/week for 10 weeks); DEX (60 mg/kg) was administered either before the 1st or 7th DAU dose (i.e. after ≈300 mg/m2 cumulative dose). While both DEX administration schedules prevented DAU-induced premature deaths and severe congestive heart failure, only the early intervention completely prevented the left ventricular dysfunction, myocardial morphological changes and mitochondrial damage. Further molecular analyses did not support the assumption that DEX cardioprotection is based and directly proportional to protection from DAU-induced oxidative damage and/or deletions in mtDNA. Nevertheless, DAU induced significant up-regulation of heme oxygenase 1 pathway while heme synthesis was inversely regulated and both changes were schedule-of-administration preventable by DEX. Early and delayed DEX interventions also differed in ability to prevent DAU-induced down-regulation of expression of mitochondrial proteins encoded by both nuclear and mitochondrial genome. Hence, the present functional, morphological as well as the molecular data highlights the enormous cardioprotective effects of DEX and provides novel insights into the molecular events involved. Furthermore, the data suggests that currently recommended delayed intervention may not be able to take advantage of the full cardioprotective potential of the drug. 相似文献
22.
23.
24.
25.
26.
27.
28.
29.
目的:探讨柠檬酸合成酶(CS)对卵巢癌线粒体DNA(mtDNA)相对拷贝数的影响。方法:Real-time PCR法检测卵巢良性肿瘤组织、卵巢癌组织及人正常卵巢上皮细胞(HOSE)和卵巢癌细胞株SKOV3、A2780中CS mRNA水平,Western blot法检测标本中CS蛋白水平。siRNA干扰SKOV3和A2780中CS表达,Real-time PCR检测干扰前后mtDNA相对拷贝数(mtND2/HBB)和线粒体转录因子A(TFAM)的变化,Western blot法检测p-ERK和p-p38水平。结果:卵巢癌组织中CS、mtDNA相对拷贝数(mtND2/HBB)和TFAM水平高于良性卵巢肿瘤组织;SKOV3和A2780细胞株中CS高于正常卵巢上皮细胞。siRNA干扰SKOV3、A2780中CS后,mtDNA相对拷贝数和TFAM水平降低,p-ERK和p-p38也降低。结论:CS在卵巢癌组织和卵巢癌细胞株中呈高表达,其水平影响卵巢癌细胞中mtDNA相对拷贝数,其机制可能与ERK/p38通路相关。 相似文献
30.
Yinping Wang Gang Wang Xin Hong Jing Zhao Dan Wu Lin Chen Xiaoli Liu Deyu Kong Qichao Huang Jinliang Xing Nan Wang Yilin Zhao 《Cancer science》2023,114(4):1464-1478