scholarly journals Synergistic Effect of Pyrvinium Pamoate and Azoles Against Aspergillus fumigatus in vitro and in vivo

2020 ◽  
Vol 11 ◽  
Author(s):  
Yi Sun ◽  
Lujuan Gao ◽  
Youwen Zhang ◽  
Ji Yang ◽  
Tongxiang Zeng
Keyword(s):  
Synergistic Effect ◽  
Aspergillus Fumigatus ◽  
Pyrvinium Pamoate

scholarly journals An in vitro and in vivo study on the synergistic effect and mechanism of itraconazole or voriconazole alone and in combination with tetrandrine against Aspergillus fumigatus

2015 ◽  
Vol 64 (9) ◽  
pp. 1008-1020 ◽  
Author(s):  
Shui-Xiu Li ◽  
Yan-Jun Song ◽  
Ling-Ling Zhang ◽  
Jian-Ping Shi ◽  
Zheng-Lai Ma ◽  
...  
Keyword(s):  
Synergistic Effect ◽  
Aspergillus Fumigatus ◽  
In Vivo Study

Azole-resistant and -susceptible Aspergillus fumigatus isolates show comparable fitness and azole treatment outcome in immunocompetent mice

2017 ◽  
Vol 56 (6) ◽  
pp. 703-710
Author(s):  
Michaela Lackner ◽  
Günter Rambach ◽  
Emina Jukic ◽  
Bettina Sartori ◽  
Josef Fritz ◽  
...  
Keyword(s):  
Body Weight ◽  
Aspergillus Fumigatus ◽  
Severe Disease ◽  
Weight Ratio ◽  
Clinical Parameters ◽  
Fitness Advantage ◽  
Significant Difference ◽  
Immunocompetent Mice

Abstract No data are available on the in vivo impact of infections with in vitro azole-resistant Aspergillus fumigatus in immunocompetent hosts. Here, the aim was to investigate fungal fitness and treatment response in immunocompetent mice infected with A. fumigatus (parental strain [ps]) and isogenic mutants carrying either the mutation M220K or G54W (cyp51A). The efficacy of itraconazole (ITC) and posaconazole (PSC) was investigated in mice, intravenously challenged either with a single or a combination of ps and mutants (6 × 105 conidia/mouse). Organ fungal burden and clinical parameters were measured. In coinfection models, no fitness advantage was observed for the ps strain when compared to the mutants (M220K and G54W) independent of the presence or absence of azole-treatment. For G54W, M220K, and the ps, no statistically significant difference in ITC and PSC treatment was observed in respect to fungal kidney burden. However, clinical parameters suggest that in particular the azole-resistant strain carrying the mutation G54W caused a more severe disease than the ps strain. Mice infected with G54W showed a significant decline in body weight and lymphocyte counts, while spleen/body weight ratio and granulocyte counts were increased. In immunocompetent mice, in vitro azole-resistance did not translate into therapeutic failure by either ITC or PSC; the immune system appears to play the key role in clearing the infection.

scholarly journals Efficient Clearance of Aspergillus fumigatus in Murine Lungs by an Ultrashort Antimicrobial Lipopeptide, Palmitoyl-Lys-Ala-dAla-Lys

2008 ◽  
Vol 52 (9) ◽  
pp. 3118-3126 ◽  
Author(s):  
Alexandra Vallon-Eberhard ◽  
Arik Makovitzki ◽  
Anne Beauvais ◽  
Jean-Paul Latgé ◽  
Steffen Jung ◽  
...  
Keyword(s):  
Invasive Aspergillosis ◽  
Aspergillus Fumigatus ◽  
Microscopic Analysis ◽  
Current Standard ◽  
New Family ◽  
Therapeutic Properties ◽  
Survival Assay ◽  
Opportunistic Fungal Pathogen

ABSTRACT Aspergillus fumigatus is an opportunistic fungal pathogen responsible for invasive aspergillosis in immunocompromised individuals. The inefficiency of antifungal agents and high mortality rate resulting from invasive aspergillosis remain major clinical concerns. Recently, we reported on a new family of ultrashort cationic lipopeptides active in vitro against fungi. Mode of action studies supported a membranolytic or a detergent-like effect. Here, we screened several lipopeptides in vitro for their anti-A. fumigatus activity. To investigate the therapeutic properties of the selected peptides in vivo, we challenged immunosuppressed C57BL/6 wild-type mice intranasally with DsRed-labeled A. fumigatus conidia and subsequently treated the animals locally with the lipopeptides. Confocal microscopic analysis revealed the degradation of DsRed-labeled hyphal forms and residual conidia in the lungs of the mice. The most efficient peptide was tested further using a survival assay and was found to significantly prolong the life of the treated animals, whereas no mice survived with the current standard antifungal treatment with amphotericin B. Moreover, as opposed to the drug-treated lungs, the peptide-treated lungs did not display any toxicity of the peptide. Our results highlight the potential of this family of lipopeptides for the treatment of pulmonary invasive aspergillosis.

scholarly journals ACT001, a novel PAI-1 inhibitor, exerts synergistic effects in combination with cisplatin by inhibiting PI3K/AKT pathway in glioma

2019 ◽  
Vol 10 (10) ◽  
Author(s):  
Xiaonan Xi ◽  
Ning Liu ◽  
Qianqian Wang ◽  
Yahui Chu ◽  
Zheng Yin ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Synergistic Effect ◽  
Glioma Cell ◽  
Synergistic Effects ◽  
Akt Pathway ◽  
Phase I Clinical Trials ◽  
Glioma Cell Proliferation ◽  
Pai 1

Abstract PAI-1 plays significant roles in cancer occurrence, relapse and multidrug resistance and is highly expressed in tumours. ACT001, which is currently in phase I clinical trials for the treatment of glioblastoma (GBM). However, the detailed molecular mechanism of ACT001 is still unclear. In this study, we investigated the effects of ACT001 on glioma cell proliferation and clarified its mechanism. We discovered that PAI-1 was the direct target of ACT001 by a cellular thermal shift assay. Then, the interaction between ACT001 and PAI-1 was verified by Biacore assays, thermal stability assays and ACT001 probe assays. Furthermore, from the proteomic analysis, we found that ACT001 directly binds PAI-1 to inhibit the PI3K/AKT pathway, which induces the inhibition of glioma cell proliferation, invasion and migration. Moreover, the combination of ACT001 and cisplatin showed a synergistic effect on the inhibition of glioma in vitro and in vivo. In conclusion, our findings demonstrate that PAI-1 is a new target of ACT001, the inhibition of PAI-1 induces glioma inhibition, and ACT001 has a synergistic effect with cisplatin through the inhibition of the PAI-1/PI3K/AKT pathway.

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