Purpose: Currently, the paucity of classical effective pharmacological drugs to treat esophageal squamous cell carcinoma (ESCC) is a major problem. The c-Myc (MYC) protein is a promising target as it is overexpressed in ESCC. MYC is a sensitive client protein of the heat shock protein 90 (HSP90) and, therefore, targeting the HSP90-MYC axis by inhibition of HSP90 is a potential therapeutic strategy for ESCC. Here, we evaluated the clinical application value of the HSP90 inhibitor (Ganetespib, STA-9090) as an anti-cancer agent for MYC-positive ESCC. Materials and Methods: We first analyzed ESCC tissue microarrays and clinical tissue samples to determine MYC expression. The relationship between MYC and HSP90 was analyzed by co-immunoprecipitation assays and immunofluorescence. In in vitro cell models, cell growth was analyzed using the CCK-8 kit, and MYC protein expression was analyzed by Western blot. The in vivo antitumor activity of STA-9090 was assessed in two xenograft animal models. Results: We demonstrated that MYC-overexpressing ESCC cells were highly sensitive to STA-9090 treatment through suppressing ESCC cell proliferation, cell cycle progression and survival. Moreover, STA-9090 treatment decreased MYC expression, reducing the half-life of the MYC protein. We further established two xenograft mouse models using ESCC cells and clinical ESCC samples to validate the effectiveness of STA-9090 in vivo. In both xenograft models, STA-9090 substantially inhibited the growth of MYC-positive ESCC tumors in vivo. In contrast, STA-9090 treatment demonstrated no beneficial effects in mice with low-MYC expressing ESCC tumors. Conclusion: In conclusion, our data support that the HSP90 inhibitor, STA-9090, suppresses the expression of the MYC protein and interferes with HSP90-MYC protein-protein interaction. This, in turn, leads to inhibition of ESCC cell proliferation and promotion of apoptosis in ESCC cells in vitro and reduction of ESCC tumors in vivo. We propose, based on our findings, that STA-9090 is a potential novel therapeutic target for MYC-positive ESCC.
In order to prepare self-supporting faujasite (FAU) zeolite, a self-supporting zeolite block was synthesized in situ by hydrothermal treatment of a metakaolin base geopolymer. The effects of hydrothermal conditions such as hydrothermal alkalinity, temperature and time on the phase composition, microstructure and mechanical strength of the hydrothermal samples were investigated and evidenced by a series of characterization methods such as X-ray diffraction (XRD), scanning electron microscopy (SEM), and Brunauer-Emmet-Teller (BET). The results showed that a self-supporting faujasite block could be obtained by hydrothermal treatment of the geopolymer block in 2 M NaOH solution at 90 °C for 24 h, which had high crystallinity, regular morphology and high compressive strength. The self-supporting zeolite block had a compressive strength of 11.7 MPa, a pore volume of 0.24 cm3/g, and an average pore diameter of 7.86 nm. The specific surface area and the microporous specific surface area of the self-supporting faujasite blocks were 80.36 m2/g and 19.7 m2/g, respectively.
preliminary efficacy is evaluated per RECIST version 1.1 criteria. This analysis will focus on results from CCA patients enrolled in dose-escalation cohorts of the FIH study. abstracts Annals of Oncology Volume 32 -Issue S3 -2021 S187
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