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排序方式: 共有125条查询结果,搜索用时 109 毫秒
121.
Roderich Walter Paula L. Huffman Allen C. Church Josefa B. Flexner Louis B. Flexner 《Hormones and behavior》1982,16(2):234-244
The cyclized derivative of the C-terminal dipeptide of arginine vasopressin (AVP), cyclo(Arg-Gly), can, when administered peripherally, block puromycininduced amnesia in mice. The potency and time course of action of this peptide are very similar to that of the parent hormone, AVP. Radioactively labelled cyclo(Arg-Gly), injected sc, was found to be degraded mainly by kidney and liver, and both intact peptide and degradation products reached the brain. However, cyclo(Arg-Gly) injected directly into brain was stable for up to 24 hr. The disappearance of cyclo(Arg-Gly) from plasma and brain was biphasic, with halflives longer than that reported for AVP. The results suggest that cyclo(Arg-Gly), formed in vivo from AVP, could contribute to the long-term effects of AVP in the CNS. However, not all of the actions of the hormone can be attributed to formation of longer-acting derivatives, and it is postulated that separate receptors may exist in brain for the neurohypophyseal hormones and their active fragments. 相似文献
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Md Sazzad Hassan Niranjan Awasthi Jun Li Fiona Williams Margaret A. Schwarz Roderich E. Schwarz Urs von Holzen 《Translational oncology》2018,11(2):426-435
Esophageal adenocarcinoma (EAC) is the fastest growing cancer in the western world and the overall 5 year survival rate of EAC is below 20%. Most patients with EAC present with locally advanced or widespread metastatic disease, where current treatment is largely ineffective. Therefore, new therapeutic approaches are urgently needed. Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) is a novel albumin-stabilized, cremophor-free and water soluble nanoparticle formulation of paclitaxel, and the potential role of nab-paclitaxel has not been tested yet in experimental EAC. Here we tested the antiproliferative and antitumor efficacy with survival advantage of nab-paclitaxel as monotherapy and in combinations in in-vitro, and in murine subcutaneous xenograft and peritoneal metastatic survival models of human EAC. Nab-paclitaxel significantly inhibited in-vitro cell proliferation with higher in-vivo antitumour efficacy and survival benefit compared to paclitaxel or carboplatin treatments both in mono- and combination therapies. Nab-paclitaxel treatment increased expression of mitotic-spindle associated phospho-stathmin, decreased expression of proliferative markers and enhanced apoptosis. This study demonstrates that nab-paclitaxel had stronger antiproliferative and antitumor activity in experimental EAC than the current standard chemotherapeutic agents which supports the rationale for its clinical use in EAC. 相似文献
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ukasz Mazurek Dmitry Ghilarov Elizabeth Michalczyk Zuzanna Pakosz Mikhail Metelev Wojciech Czyszczo Karolina Wawro Iraj Behroz Svetlana Dubiley Roderich D Süssmuth Jonathan G Heddle 《Nucleic acids research》2021,49(3):1581
DNA gyrase, a type II topoisomerase found predominantly in bacteria, is the target for a variety of ‘poisons’, namely natural product toxins (e.g. albicidin, microcin B17) and clinically important synthetic molecules (e.g. fluoroquinolones). Resistance to both groups can be mediated by pentapeptide repeat proteins (PRPs). Despite long-term studies, the mechanism of action of these protective PRPs is not known. We show that a PRP, QnrB1 provides specific protection against fluoroquinolones, which strictly requires ATP hydrolysis by gyrase. QnrB1 binds to the GyrB protein and stimulates ATPase activity of the isolated N-terminal ATPase domain of GyrB (GyrB43). We probed the QnrB1 binding site using site-specific incorporation of a photoreactive amino acid and mapped the crosslinks to the GyrB43 protein. We propose a model in which QnrB1 binding allosterically promotes dissociation of the fluoroquinolone molecule from the cleavage complex. 相似文献