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Fungal allergens
Published in Richard F. Lockey, Dennis K. Ledford, Allergens and Allergen Immunotherapy, 2020
Robert E. Esch, Jonathan A. Bernstein, Hari M. Vijay
Tri t 1 is a 30 kDa major allergen of T. tonsurans to which 54% of Trichophyton-sensitized, skin test-positive and 73% of RAST-positive patients possess IgE antibodies [236]. The allergen has a sequence similarity to S. cerevisiae exo 1,3-β-glucanase [237] The Trichophyton group 4 allergens have been identified in T. tonsurans (Tri t 4) and T. rubrum (Tri r 4) as an 83 kDa protein associated with DTH skin test reactions. The cloned and sequenced rTri r 4 [238] showed limited sequence identity to the prolyl oligopeptidase family of serine proteinases. Tri r 2 was also cloned and sequenced [238], and the 29 kDa protein has a high degree of sequence identity to the subtilase enzyme family.
Research progress on therapeutic targeting of quiescent cancer cells
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2019
Jinhua Zhang, Jing Si, Lu Gan, Cuixia Di, Yi Xie, Chao Sun, Hongyan Li, Menghuan Guo, Hong Zhang
MG132 has been shown to enhance irradiation-induced apoptosis by suppressing activation of NF-κB and tumor growth [57]. However, other reports suggest that proteasome inhibition with MG-132 or bortezomib induces G0–G1 phase arrest in MM cells, resulting in lower sensitivity of tumor cells to treatment and survival [5,63]. Recent experiments have demonstrated that MG132-treated proliferating fibroblasts undergo rapid apoptosis whereas MG132-treated quiescent cells mostly retain viability through induction of a variety of alternative protective mechanisms (including ROS-detoxifying pathways, clearance of ubiquitinated protein aggregates, and the Baf-sensitive autophagy/lysosomal pathway) to escape proteasome inhibition-mediated cell death. Hence, increasing cellular superoxide concentrations with 2-methoxyestradiol or inhibition of autophagy/lysosomal pathways with bafilomycin A1 could sensitize quiescent fibroblasts to MG132-mediated apoptosis [5]. Furthermore, MM cells that survive bortezomib treatment exhibit a GRP78high/p21high/CDK6low/pRblow profile, which may distinguish quiescent MM cells capable of spawning tumor recurrence [62]. Upregulation of the pro-survival chaperone, BiP/Grp78, an unfolded protein response (UPR) survival factor, facilitates prolonged survival of quiescent cancer cells, which may serve as a reliable target to eradicate residual tumor cells [62,64]. Subtilase cytotoxin, a bacterial AB5 toxin, specifically downregulates GRP78 and induces death of bortezomib-surviving MM cells [62]. Moreover, the Hsp90 inhibitor, IPI-504, increases bortezomib sensitivity in mantle cell lymphoma cultures and tumors via BiP/Grp78 downregulation and UPR inhibition [64]. Several studies have shown that YM155, a small-molecule inhibitor of survivin, exerts a strong cytotoxic effect on quiescent MM and bortezomib-resistant cells by suppressing survivin and Mcl-1 [65]. Additionally, maintaining eukaryotic initiation factor 2α in a hyperphosphorylation state potentiates bortezomib efficiency and eliminates residual quiescent MM cells after proteasome inhibition [63]. In summary, strategies that aid in overcoming proteasome inhibitor resistance or eliminating surviving quiescent tumor cells after proteasome inhibition may ultimately contribute to reducing residual disease and recurrence in various types of cancer.