Virtual Library
Start Your Search
Xiyi Lu
Author of
-
+
P2.01 - Advanced NSCLC (Not CME Accredited Session) (ID 950)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
-
+
P2.01-69 - EZH2-Mediated Epigenetic Suppression Of GDF15 Predicts a Poor Prognosis and Regulates Cell Proliferation in Non-Small Cell Lung Cancer (ID 12457)
16:45 - 18:00 | Presenting Author(s): Xiyi Lu
- Abstract
Background
Growth differentiation factor 15 (GDF15), a member of the TGF-β superfamily of cytokines, has been reported to exert very heterogeneous functions in various tumors. However, the role of GDF15 and its underlying mechanism in mediating non-small cell lung cancer (NSCLC) progression remain unknown.
a9ded1e5ce5d75814730bb4caaf49419 Method
GDF15 expression level was analyzed in 66 NSCLC tissues by quantitative reverse transcription PCR (qRT-PCR). The effect of GDF15 on proliferation was evaluated by MTT and colony formation assays, flow cytometric analysis. NSCLC cells transfected with pcDNA-GDF15 or empty vector were injected into nude mice to study the effect of GDF15 on tumorigenesis in vivo. Chromatin immunoprecipitation (ChIP) assay was used to investigate the mechanism of action of GDF15 in the NSCLC cells.
4c3880bb027f159e801041b1021e88e8 Result
In this study, we found that GDF15 is down-regulated in paired NSCLC tissues and is correlated with poor clinical outcomes in NSCLC. Further experiments demonstrated that overexpression of GDF15 significantly repressed NSCLC proliferation both in vitro and in vivo. Mechanistic studies reveal that inhibition of EZH2 expression prevented its binding to the GDF15 promoter region and reduced the trimethylation modification pattern of H3K27.
8eea62084ca7e541d918e823422bd82e Conclusion
Together, our data uncover that GDF15 is a direct target of EZH2, and as a regulator of proliferation, might serve as a candidate prognostic biomarker and target for new therapies in human NSCLC.
6f8b794f3246b0c1e1780bb4d4d5dc53
-
+
P2.13 - Targeted Therapy (Not CME Accredited Session) (ID 962)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 2
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
-
+
P2.13-29 - IL-22 Confers Resistance To EGFR-TKIs In Non-Small Cell Lung Cancer Bearing EGFR Gene Mutation and Amplification (ID 11857)
16:45 - 18:00 | Presenting Author(s): Xiyi Lu
- Abstract
Background
The effect of epidermal growth factor receptor(EGFR)-targeted strategy is hindered by drug resistance. IL-22 can promote tumor growth and induce resistance to chemotherapy in human lung cancer cells. The aim of our study was to investigate the mechanism of IL-22-induced resistance to EGFR-tyrosine kinase inhibitors(EGFR-TKIs)in the NSCLC.
a9ded1e5ce5d75814730bb4caaf49419 Method
The tissues and plasma of patients taking EGFR-TKIs were used to examine the correlation between the drug’s efficacy and IL-22 level. We identified IL-22-induced EGFR-TKIs resistance and the effect of IL-22 on EGFR/AKT/ERK pathways in NSCLC PC-9 and HCC827 cells by CCK-8 assay, flow cytometric analysis, and western blotting. Then, we established the PC-9 xenograft model with IL-22 exposure and used gefitinib combined with vehicle or IL-22 to treat mice.
4c3880bb027f159e801041b1021e88e8 Result
We confirmed that IL-22 can inhibit the effect of gefitinib on NSCLC cells and determined the effects of IL-22 on EGFR/AKT/ERK pathways. Then, we showed that IL-22 exposures could promote tumor growth and induce resistance to gefitinib in the PC-9 xenograft model.
8eea62084ca7e541d918e823422bd82e Conclusion
These results suggest that IL-22 contributes to tumor progression and EGFR-TKIs resistance in NSCLC. Therefore, IL-22 is a potential therapeutic target for EGFR-TKIs resistance.
6f8b794f3246b0c1e1780bb4d4d5dc53 -
+
P2.13-34 - Long Intergenic Non-Coding RNA 00665 Induces Acquired Resistance to Gefitinib in Non-Small-Cell Lung Cancer (ID 11903)
16:45 - 18:00 | Presenting Author(s): Xiyi Lu
- Abstract
Background
Gefitinib, a tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR-TKI), has been used as the first choice of treatment for advanced non-small cell lung cancer (NSCLC). However, during the course of treatment cancer cells often develop resistance to gefitinib without fully understood mechanisms. In recent years, numerous studies have shown that long non-coding RNAs (lncRNAs) play vital roles in modulating various biological processes, such as cell apoptosis, proliferation, migration, and invasion. Nevertheless cancer drug resistance mechanisms related to LncRNAs and their important roles in cancer development are still poorly understood. In this study, we aimed to elucidate an important role of long intergenic non-coding RNA 00665 (LINC00665) in developing resistance to gefitinib in NSCLC.
a9ded1e5ce5d75814730bb4caaf49419 Method
Quantitative reverse transcription PCR (qRT-PCR) was performed to examine the expression levels of LINC00665 in 10 pairs of LUAD tissues from patients who had never been treated with gefitinib (NG) and those who were treated with gefitinib but developed resistance (GR). The effect of LINC00665 on proliferation and apoptosis in gefitinib-resistant cells was evaluated by CCK8, colony formation, flow-cytometric analysis and in vivo tumor formation assays. Western-blot and immunohistochemistry were used to evaluate the expression of EGFR and its downstream event.
4c3880bb027f159e801041b1021e88e8 Result
LINC00665 expression levels were significantly increased in NSCLC patients who developed acquired resistance to gefitinib compared to the NG group.Furthermore, LINC00665 inhibition reversed gefitinib sensitivity both in vitro and in vivo by suppressing cell growth and induced cell apoptosis. Importantly, knockdown of LINC00665 marked decreased activation of EGFR and its downstream event Akt and ERK1/2.
8eea62084ca7e541d918e823422bd82e Conclusion
Taken together,our study demonstrates that LINC00665 may be a potential biomarker of response to gefitinib as well as a novel therapeutic target for future treatment of NSCLC.
6f8b794f3246b0c1e1780bb4d4d5dc53
-
+
P3.13 - Targeted Therapy (Not CME Accredited Session) (ID 979)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
-
+
P3.13-23 - EGFR-TKIs Combined Hydroxycamptothecin Improved Outcomes in EGFR-Mutant NSCLC Patients Who Harboring Pericardial Effusion. (ID 12491)
12:00 - 13:30 | Presenting Author(s): Xiyi Lu
- Abstract
Background
Pericardial perfusion of hydroxycamptothecin (PCPH) is the effective treatment for malignant pericardial effusion(MPCE). Epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs) have shown greater efficacy in clinical trials than chemotherapy in patients with EGFR-mutant non-small cell lung cancer (NSCLC), but little information is available on EGFR-mutant NSCLC patients who harboring MPCE. We therefore investigate the advantage of EGFR-TKIs with PCPH for these patients.
a9ded1e5ce5d75814730bb4caaf49419 Method
We enrolled patients with MPCE, stage Ⅳ, EGFR-mutant (exon 19 deletion or exon 21 Leu858Arg) NSCLC. These patients were divided into 2 groups by different treatments: EGFR-TKIs in combination with PCPH and chemotherapy combined with PCPH. Retrospectively analyzed the survival of different treatment programs and their prognostic factors.
4c3880bb027f159e801041b1021e88e8 Result
Between January 1, 2010, and December 31, 2016, 644 patients were screened. MPCE occurred more frequently in patients with EGFR-mutant than those with EGFR wild-type (10.62% vs. 5.20%; p = 0.046). 29 patients were enrolled, 15 to EGFR-TKIs/HCPT group and 14 to chemotherapy/HCPT group. The progression free survival (PFS) was significantly longer with EGFR-TKIs/HCPT group (360 days) than chemotherapy/HCPT group (90 days; P=0.003). The effusion control rate for pericardial lesions showed statistical difference between two groups (93.33% vs. 71.43%, P = 0.038). Toxicity of EGFR-TKIs/ HCPT groups were characterized by skin rash (40.0% vs. 7.1%; P=0.039), whereas the proportions of patients with leucopenia (42.9% vs. 6.7%; P=0.023) and thrombocytopenia (42.9% vs. 6.7%; P=0.023) were higher in chemotherapy/HCPT group.
8eea62084ca7e541d918e823422bd82e Conclusion
EGFR-TKIs combined with PCPH is preferable for advanced NSCLC patients with EGFR-mutant and MPCE.
6f8b794f3246b0c1e1780bb4d4d5dc53
