Objective: This study aims to assess the efficacy of diffusion-weighted (DW) and T1-weighted (T1W) magnetic resonance imaging (MRI) combined with high-resolution computed tomography (HRCT) (together as DW-T1W-CT) in the preoperative evaluation of the presence and extent of cholesteatoma, which helps determine whether a patient is suitable for transcanal endoscopic ear surgery (TEES). Methods: This retrospective study included 35 patients (18 male and 17 female) aged from 2 to 81 years diagnosed with chronic otitis media with or without cholesteatoma, who had received surgical treatment and a preoperative MRI and HRCT during the period of December 2015 to December 2020 at Cathay General Hospital. We compared the preoperative DW-T1W-CT findings with the intraoperative findings and final pathologic diagnosis. The accurate predictive value was evaluated using the presence of cholesteatoma and its extent. Results: Regarding the efficacy of detecting cholesteatoma, we found a sensitivity of 92% (23/25 cases with cholesteatoma), a specificity of 90% (9/10 cases without cholesteatoma), and an overall accurate predictive value of 91.4% (32/35) by using combined DW-T1W-CT imaging. With regard to evaluating the extent of cholesteatoma, the combined DW-T1W-CT images obtained an accurate predictive value of 84% (21/25 cases of cholesteatoma). Conclusion: Combined DW-T1W-CT has been proven to be a reliable tool in detecting the presence of cholesteatoma. It is also useful in preoperatively depicting the extent of cholesteatoma, which is crucial for determining whether a patient is suitable for TEES, aiding in surgical planning and patient consultation.
Background
Resistance to chemotherapeutic drugs is a key factor for cancer recurrence and metastases in head and neck cancer (HNC). Cancer stem cells (CSCs) in tumors have self-renewal, differentiation, and higher drug resistance capabilities, resulting in a poor prognosis for patients. In glucose metabolism, pyruvate dehydrogenase kinase (PDK) inhibits pyruvate dehydrogenase and impedes pyruvate from being metabolized into acetyl-CoA and entering the tricarboxylic acid cycle to generate energy. Studies have reported that PDK1 and PDK2 inhibition suppresses the growth, motility, and drug resistance of cancer cells. Furthermore, while TGFβ1 levels are persistently elevated in HNC patients with poor prognosis, the role of PDK isoforms in the TGFβ1-promoted progression and stem-like properties of HNC is unclear.
Methods
Levels of PDK1 and PDK2 were evaluated in HNC tissue microarrays by immunohistochemistry to explore potential clinical relevance. PDK1 and PDK2 were knocked down by the lentivirus shRNA system to investigate their role in TGFβ1-promoted tumor progression in vitro.
Results
We found that PDK2 levels were increased in the later stage of HNC tissues compared to constant PDK1 expression. After PDK1 and PDK2 knockdown, we discovered increased ATP production and decreased lactate production in TGFβ1-treated and untreated HNC cells. However, only PDK2 silencing significantly inhibited the clonogenic ability of HNC cells. We subsequently found that TGFβ1-promoted migration and invasion capabilities were decreased in PDK1 and PDK2 knockdown cells. The tumor spheroid-forming capability, motility, CSC genes, and multidrug-resistant genes were downregulated in PDK1 and PDK2 silencing CSCs. PDK1 and PDK2 inhibition reversed cisplatin and gemcitabine resistance of CSCs, but not paclitaxel resistance.
Conclusion
The results demonstrated that the PDK1- and PDK2-mediated Warburg effect contributes to the TGFβ1-enhanced stemness properties of HNC. Therefore, PDK1 and PDK2 may serve as molecular targets for the combination therapy of HNC.
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.