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Yu-Chung Wu



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    EP1.17 - Treatment of Early Stage/Localized Disease (ID 207)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Treatment of Early Stage/Localized Disease
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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      EP1.17-28 - Electromagnetic Navigation-Guided Preoperative Localization for Small Malignant Pulmonary Tumors (Now Available) (ID 264)

      08:00 - 18:00  |  Author(s): Yu-Chung Wu

      • Abstract
      • Slides

      Background

      Surgical removal of non-visible, non-palpable small pulmonary nodules is sometimes challenging during video-assisted thoracoscopic surgery (VATS) and preoperative nodule localization is of paramount importance for precise resection. We reported our experience of preoperative localization using the SPiN thoracic electromagnetic navigation system.

      Method

      The inclusion criteria include: 1. Patients with highly suspicious malignant pulmonary nodules according to persistent or progressive nature on follow-up CT scans, or history of extrathoracic malignancy. 2. Target nodule size less than two centimeters. 3. Presumed to be non-visible and non-palpable during VATS according to surgeon`s judgement. 4. Patients who received electromagnetic navigation for preoperative localization. As the SPiN system allows for both transbronchial (endobronchial) and transthoracic (percutaneous) routes, the optimal approach was decided according to the location of target nodule.The preoperative localization and thoracoscopic resection were performed in the same operation room by the same team. The successful localization was defined as successful identification of target tumors during VATS procedure without palpation.

      Result

      From Jun 2018 to March 2019, a total of 30 patients with 35 nodules were included. Thirty-one percutaneous and five endobronchial approaches were performed. One patient received both approaches for the same tumor. Three patients received both percutaneous and endobronchial approaches for multiple targets localization. The mean nodule size was 9.6 ±3.5 mm. The materials used for marking included dye (n = 18), micorcoil (n = 4), indocyanine green (ICG, n = 2), microcoil + dye (n = 8), and microcoil + ICG (n = 3). There was no localization-related adverse event. Successful localization was achieved in 27 of 30 (90.0%) patients and 32 of 33 35 (91.4%) nodules. In three patients, localization failed as dye extravasation in the pleural cavity without any stains in the subpleural parenchyma. The pathological diagnosis included metastatic tumors (n = 6), primary pulmonary squamous cell carcinoma (n = 2), and primary pulmonary adenocarcinoma (invasive adenocarcinoma, n = 9; minimally invasive adenocarcinoma, n = 12; adenocarcinoma in situ, n = 6).

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      Conclusion

      We reported our experience of electromagnetic navigation-guided transbronchial and transthoracicpreoperative localization for small malignant pulmonary tumors. Lessons from failed cases were learned and localization techniques were modified to improve successful localization rate.

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    MA15 - Usage of Computer and Molecular Analysis in Treatment Selection and Disease Prognostication (ID 141)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Pathology
    • Presentations: 1
    • Now Available
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      MA15.01 - Cellular Prion Protein Transcriptionally Regulated by NFIL3 Enhances Lung Cancer Cell Lamellipodium Formation and Migration (Now Available) (ID 151)

      15:45 - 17:15  |  Author(s): Yu-Chung Wu

      • Abstract
      • Presentation
      • Slides

      Background

      Tumor invasion and metastasis are the major causes of treatment failure and mortality in lung cancer patients. However, the precise molecular targets responsible for tumor invasion remain unclear.

      Method

      In this study, we identified a group of genes with differential expression in in situ and invasive lung adenocarcinoma tissues by cDNA microarray analysis; among these genes we further characterized the association of the upregulation of PRNP, the gene encoding cellular Prion protein (PrPc), with lung adenocarcinoma invasiveness through immunohistochemistry and in situ hybridization analysis on clinical tissues. The roles of PrPc in lung cancer cell lines were also verified by using immunofluorescence staining, in vitro transwell assay and in vivo metastasis mouse model. In addition, the impact of PrPc on the activation of the JNK signaling pathway was investigated by Western blot analysis. Finally, luciferase reporter assay and chromatin immunoprecipitation assay were used to identify the transcriptional activators of PRNP.

      Result

      Immunohistochemistry on clinical specimens showed association of PrPc expression with invasive but not in situ lung adenocarcinoma. Consistently, the expression of PrPc was higher in the highly invasive than in the lowly invasive lung adenocarcinoma cell lines. Knockdown of PrPc expression in cultured lung adenocarcinoma cells decreased their lamellipodium formation, in vitro migration and invasion, and in vivo experimental lung metastasis. Phosphorylation of JNKs was found to correlate with PrPc expression and the inhibition of JNKs suppressed the PrPc-induced up-regulation of lamellipodium formation, cell migration, and invasion. Moreover, we identified the nuclear factor, interleukin 3 regulated (NFIL3) protein as a transcriptional activator of the PRNP promoter. Accordingly, NFIL3 promoted lung cancer cell migration and invasion in a PrPc-dependent manner. High NFIL3 expression in clinical specimens of lung adenocarcinoma was also associated with tumor invasiveness and poor survival of patients.

      Conclusion

      Our observations suggest that PRNP expression is associated with the invasiveness of lung adenocarcinoma, and cell line model demonstrated that PrPc serves as a critical factor for lung cancer cell lamellipodia formation, migration and invasion via JNK signaling. A novel transcription factor, NFIL3, was identified to upregulate PRNP expression in lung cancer cells; further characterizations showed that NFIL3 promotes lung cancer cell migration through PrPc-dependent manner. Moreover, high NFIL3 expression was found to be associated with lung cancer invasiveness in clinical tissues. Overall, NFIL3/PrPc axis plays a critical role in lung cancer invasiveness and metastasis, and may be the potential therapeutic targets in the future.

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