Abstract. This study was designed to clarify the long-term efficacy and safety of percutaneous ethanol injection (PEI) therapy in benign nodular and cystic thyroid diseases, and to evaluate response by criteria defined as disappearance of hot nodule. Solid nodule and complex cyst were classified into three groups in accordance with volume reduction. In autonomously functioning thyroid nodule (AFTN), disappearance of hot nodule with normalization of thyroid hormone level and restored extra-nodular uptake was defined to be curative. In solid nodule (n = 198) and complex cyst (n = 432), initial volume was significantly reduced to post-PEI and final volumes, and volume reduction persisted during follow-up period. Complete response, partial response and no response were as follows: 17.2%, 71.7%, 11.1% in solid nodule; 19.0%, 60.4%, 20.6% in complex cyst, respectively. Differences of volume reduction according to initial volume (³10 mL vs. <10 mL) were significant. Correlations between initial and final volumes, and between initial volume and volume reduction were also significant. In 24 patients with AFTN, when effectiveness was assessed by disappearance of hot nodule, only 1 case was curative. Reexpansion or recurrence was observed in 5 cases. Complications developed in 9.0% but there was no permanent or serious complication in this study. In conclusion, our data suggest that PEI therapy could be an effective and safe therapeutic modality for benign nodular and cystic thyroid diseases especially when initial volume is more than 10 mL, but may not induce disappearance of hot nodule itself in AFTN.
The effect of 17-allylamino-17-demethoxygeldanamycin (17-AAG), an hsp90 inhibitor, alone or in combination with paclitaxel on survival of anaplastic thyroid carcinoma (ATC) was evaluated. In 8505C and CAL62 cells, after treatment of 17-AAG, cell viability decreased, and the percentage of dead cells increased. 17-AAG did not cause cleavage of caspase-3 protein, and change expression of IAPs. Pretreatment of z-VAD-fmk did not alter cell viability and the percentage of dead cells. In 17-AAG-treated cells, knockdown of p53 rescued growth inhibition, while cycloheximide attenuated cell death. When cells were treated with both 17-AAG and paclitaxel, all of the combination index values were higher than 1, indicating antagonism between 17-AAG and paclitaxel. In 17-AAG- and paclitaxel-treated cells, compared with paclitaxel alone-treated cells, the protein levels of hsp90, hsp70, and hsc70 increased. In conclusion, our results suggest that 17-AAG induces non-apoptotic cell death requiring de novo protein synthesis in ATC cells. Moreover, these results demonstrate that 17-AAG antagonizes paclitaxel with concomitant alterations in hsp90 client proteins in ATC cells.
Our results demonstrate that AUY922 potently induces cytotoxicity with concomitant modulation of hsp90 client proteins in ATC cells. Moreover, AUY922 has a synergistic activity with PXD101 in induction of cytotoxicity in conjunction with the inactivation of PI3K/Akt signaling and survivin and the activation of DNA damage response in ATC cells.
The influence of the heat shock protein 90 (hsp90) inhibitor SNX5422 alone or in combination with the histone deacetylase (HDAC) inhibitors PXD101, suberoylanilide hydroxamic acid (SAHA), and trichostatin A (TSA) on survival of anaplastic thyroid carcinoma (ATC) cells was investigated. In 8505C and CAL62 cells, SNX5422 caused cell death with concomitant changes in the expression of hsp90 client proteins. After treatment of both SNX5422 and PXD101, SAHA and TSA, compared with treatment of SNX5422 alone, cell viability was diminished, whereas inhibition rate and cytotoxic activity were enhanced. All of the combination index values were lower than 1.0, suggesting the synergism between SNX5422 and PXD101, SAHA and TSA in induction of cell death. In cells treated with both SNX5422 and PXD101, SAHA and TSA, compared with cells treated with SNX5422 alone, the protein levels of Akt, phospho-4EBP1, phospho-S6 K, and survivin were diminished, while those of γH2AX, acetyl. histone H3, acetyl. histone H4, cleaved PARP, and cleaved caspase-3 were enhanced. In conclusion, these results demonstrate that SNX5422 has a cytotoxic activity in conjunction with alterations in the expression of hsp90 client proteins in ATC cells. Moreover, SNX5422 synergizes with HDAC inhibitors in induction of cytotoxicity accompanied by the suppression of PI3K/Akt/mTOR signaling and survivin, and the overexpression of DNA damage-related proteins in ATC cells.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.