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991.
《Research in social & administrative pharmacy》2020,16(2):238-248
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La-Wei Yang Xian-Jin Wu Yi Liang Guang-Qing Ye Yuchuan Che Xue-Zhen Wu Xiao-Jie Zhu Huo-Liang Fan Xiang-Ping Fan Jun-Fa Xu 《Molecular carcinogenesis》2020,59(4):447-461
Effective therapeutic targets for triple-negative breast cancer (TNBC), a special type of breast cancer (BC) with rapid metastasis and poor prognosis, are lacking, especially for patients with chemotherapy resistance. Decitabine (DCA) is a Food and Drug Administration-approved DNA methyltransferase inhibitor that has been proven effective for the treatment of tumors. However, its antitumor effect in cancer cells is limited by multidrug resistance. Cancer stem cells (CSCs), which are thought to act as seeds during tumor formation, regulate tumorigenesis, metastasis, and drug resistance through complex signaling. Our previous study found that miR-155 is upregulated in BC, but whether and how miR-155 regulates DCA resistance is unclear. In this study, we demonstrated that miR-155 was upregulated in CD24−CD44+ BC stem cells (BCSCs). In addition, the overexpression of miR-155 increased the number of CD24−CD44+ CSCs, DCA resistance and tumor clone formation in MDA-231 and BT-549 BC cells, and knockdown of miR-155 inhibited DCA resistance and stemness in BCSCs in vitro. Moreover, miR-155 induced stemness and DCA resistance by inhibiting the direct target gene tetraspanin-5 (TSPAN5). We further confirmed that overexpression of TSPAN5 abrogated the effect of miR-155 in promoting stemness and DCA resistance in BC cells. Our data show that miR-155 increases stemness and DCA resistance in BC cells by targeting TSPAN5. These data provide a therapeutic strategy and mechanistic basis for future possible clinical applications targeting the miR-155/TSPAN5 signaling axis in the treatment of TNBC. 相似文献
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D.R. MacFadden B. Coburn N. Shah A. Robicsek R. Savage M. Elligsen N. Daneman 《Clinical microbiology and infection》2019,25(1):108.e1-108.e7
Objectives
Early empiric antibiotic therapy in patients can improve clinical outcomes in Gram-negative bacteraemia. However, the widespread prevalence of antibiotic-resistant pathogens compromises our ability to provide adequate therapy while minimizing use of broad antibiotics. We sought to determine whether readily available electronic medical record data could be used to develop predictive models for decision support in Gram-negative bacteraemia.Methods
We performed a multi-centre cohort study, in Canada and the USA, of hospitalized patients with Gram-negative bloodstream infection from April 2010 to March 2015. We analysed multivariable models for prediction of antibiotic susceptibility at two empiric windows: Gram-stain-guided and pathogen-guided treatment. Decision-support models for empiric antibiotic selection were developed based on three clinical decision thresholds of acceptable adequate coverage (80%, 90% and 95%).Results
A total of 1832 patients with Gram-negative bacteraemia were evaluated. Multivariable models showed good discrimination across countries and at both Gram-stain-guided (12 models, areas under the curve (AUCs) 0.68–0.89, optimism-corrected AUCs 0.63–0.85) and pathogen-guided (12 models, AUCs 0.75–0.98, optimism-corrected AUCs 0.64–0.95) windows. Compared to antibiogram-guided therapy, decision-support models of antibiotic selection incorporating individual patient characteristics and prior culture results have the potential to increase use of narrower-spectrum antibiotics (in up to 78% of patients) while reducing inadequate therapy.Conclusions
Multivariable models using readily available epidemiologic factors can be used to predict antimicrobial susceptibility in infecting pathogens with reasonable discriminatory ability. Implementation of sequential predictive models for real-time individualized empiric antibiotic decision-making has the potential to both optimize adequate coverage for patients while minimizing overuse of broad-spectrum antibiotics, and therefore requires further prospective evaluation.Summary
Readily available epidemiologic risk factors can be used to predict susceptibility of Gram-negative organisms among patients with bacteraemia, using automated decision-making models. 相似文献997.
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目的分析口腔感染患者病原菌分布及药敏情况,为临床合理用药提供参考。方法选取口腔感染患者86例作为研究对象,收集口腔分泌物进行病原菌培养,并行药敏实验。结果本组86例患者中,≤15岁、≥56岁口腔感染患者比例较高,分别占30.2%、40.7%。共检出病原菌351株,其中厌氧菌236株,占67.2%,其在厌氧菌中黑色素普氏菌比例最高(50.4%),其次为口腔链球菌(16.5%);需氧菌115株,占32.8%。对苯唑西林、头孢唑肟、庆大霉素、环丙沙星的耐药较高,分别为49.2%、46.6%、42.0%、40.2%;对万古霉素、四环素、头孢曲松的敏感性较高,分别为98.3%、95.8%、93.6%。结论厌氧菌是口腔感染较为常见的菌种,可选用万古霉素、四环素、头孢曲松等敏感性高的药物治疗。 相似文献