Chapter 14 How to activate intrinsic stress resistance mechanisms to obtain therapeutic benefit

Author(s):  
Prasanta K. Ray ◽  
Tanya Das ◽  
Gaurisankar Sa
2019 ◽  
Vol 20 (9) ◽  
pp. 2345 ◽  
Author(s):  
Mónica Galocha ◽  
Pedro Pais ◽  
Mafalda Cavalheiro ◽  
Diana Pereira ◽  
Romeu Viana ◽  
...  

Candida albicans and Candida glabrata are the two most prevalent etiologic agents of candidiasis worldwide. Although both are recognized as pathogenic, their choice of virulence traits is highly divergent. Indeed, it appears that these different approaches to fungal virulence may be equally successful in causing human candidiasis. In this review, the virulence mechanisms employed by C. albicans and C. glabrata are analyzed, with emphasis on the differences between the two systems. Pathogenesis features considered in this paper include dimorphic growth, secreted enzymes and signaling molecules, and stress resistance mechanisms. The consequences of these traits in tissue invasion, biofilm formation, immune system evasion, and macrophage escape, in a species dependent manner, are discussed. This review highlights the observation that C. albicans and C. glabrata follow different paths leading to a similar outcome. It also highlights the lack of knowledge on some of the specific mechanisms underlying C. glabrata pathogenesis, which deserve future scrutiny.


2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Mikkel G. Terp ◽  
Kirstine Jacobsen ◽  
Miguel Angel Molina ◽  
Niki Karachaliou ◽  
Hans C. Beck ◽  
...  

AbstractEGFR tyrosine kinase inhibitor (TKI) resistance in non-small cell lung cancer (NSCLC) patients is inevitable. Identification of resistance mechanisms and corresponding targeting strategies can lead to more successful later-line treatment in many patients. Using spectrometry-based proteomics, we identified increased fibroblast growth factor receptor 1 (FGFR1) expression and Akt activation across erlotinib, gefitinib, and osimertinib EGFR-TKI-resistant cell line models. We show that while combined EGFR-TKI and FGFR inhibition showed some efficacy, simultaneous inhibition of FGFR and Akt or PI3K induced superior synergistic growth inhibition of FGFR1-overexpressing EGFR-TKI-resistant NSCLC cells. This effect was confirmed in vivo. Only dual FGFR and Akt inhibition completely blocked the resistance-mediating signaling pathways downstream of Akt. Further, increased FGFR1 expression was associated with significantly lower PFS in EGFR-TKI-treated NSCLC patients, and increased FGFR1 were demonstrated in a few post- vs. pre-EGFR-TKI treatment clinical biopsies. The superior therapeutic benefit of combining FGFR and Akt inhibitors provide the rationale for clinical trials of this strategy.


Microbiology ◽  
2015 ◽  
Vol 84 (2) ◽  
pp. 152-158 ◽  
Author(s):  
A. S. Egorova ◽  
N. N. Gessler ◽  
L. P. Ryasanova ◽  
T. V. Kulakovskaya ◽  
T. A. Belozerskaya

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