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Huimin Wang
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EP1.03 - Biology (ID 193)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Biology
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.03-11 - Mechanisms of Gefitinib Plus Pemetrexed on Human Non-Small Cell Lung Cancer (Now Available) (ID 1402)
08:00 - 18:00 | Author(s): Huimin Wang
- Abstract
Background
Resistance to EGFR tyrosine kinase inhibitors (EGFR-TKI) is often acquired in non-small cell lung cancer (NSCLC) patients during treatment. We previously demonstrated that combined treatment with EGFR-TKI gefitinib plus chemotherapy improved progression-free survival (PFS) in NSCLC patients carrying sensitive EGFR mutations.
Method
Pharmacological interaction between gefitinib and pemetrexed was evaluated in NSCLC cell line PC-9 using MTT assay. The influence of combined treatment with gefitinib plus pemetrexed on gene expression profiles and signaling pathways has been investigated using microarray and Ingenuity Pathway Analysis (IPA).
Result
Synergistic inhibitory effect between gefitinib and pemetrexed was observed in NSCLC cell line PC-9. Figure 1A suggested representative proliferation inhibitory effects of gefitinib, pemetrexed and combined treatment for 48 hours. Figure 1B showed CI values of concurrent gefitinib-pemetrexed treatment in PC-9 NSCLC cell line. CI values at ED50, ED75 and ED90 were shown.
Furthermore, widespread gene expression changes and critical signaling pathways were induced significantly by combined treatment in PC-9 cells. Figure 2A was heatmap of gene expression prolifes in human NSCLC PC-9 cell line treated with gefitinib (blue), pemetrexed (purple) or gefitinib-pemetrexed combination (orange) with the criteria P<0.05 and ▏fold change ▏>1.5. Genes and samples were listed in rows and columns, respectively. A colour standard for data normalization was shown at the bottom with green representing downregulated genes while red representing upregulated genes. In Figure 2B, pathway enrichment of differential expressed genes was analysed using Ingenuity Pathway Analysis (IPA). Signaling pathways shown here were based on a P<0.0001. Figure 2C showed heatmap of critical pathways affected by combined treatment as compared to gefitinib single treatment. Heatmap colour represented the Z-score of signalling pathways. Z-score>0 meant the signalling pathway was stimulated by related treatment while Z-score<0 meant the signalling pathway was inhibited by related treatment.
Conclusion
Gene expression profiles revealed potential signaling pathways contributing to the synergism.
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P1.01 - Advanced NSCLC (ID 158)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.01-95 - Efficacy and Safety of Anlotinib in Combination with Chemotherapy as First-Line Therapy in Advanced Non-Small Cell Lung Cancer (NSCLC) Patients (ID 2296)
09:45 - 18:00 | Author(s): Huimin Wang
- Abstract
Background
Anlotinib (AL3818) is a novel multi-target angioenesis TKI targeting the VEGFR, FGFR, PDGFR and c-Kit. In the ALTER0303 trial, Anlotinib as third-line treatment significantly improved progress-free survival (PFS) and overall survival (OS) in advanced NSCLC patients. This is the first trial evaluating the combination of chemotherapy and anlotinib in treatment-naive advanced NSCLC and is one arm of Phase II anlotinib-based trial (NCT03628521).
Method
Patients with previously untreated EGFR/ALK/ROS1 negative advanced NSCLC were enrolled. Eligible patients received anlotinib (12 mg QD from day 1 to 14 of a 21-day cycle) combined with carboplatin (AUC 5) and pemetrexed (adenocarcinoma, 500mg/m2)/gemcitabine (squamous, 1.0g/m2，day1&8) for four to six cycles (21-day cycle). Maintenance treatment was followed by using pemetrexed and anlotinib (anlotinib alone for squamous) until disease progression or treatment intolerance. The primary outcome was objective response (ORR) and secondary outcomes were PFS, disease control rate (DCR) and OS.
Result
Until the 21st March 2019, the curative effect was assessed in 30 enrolled patients according to the RECIST 1.1. Among these patients, eighteen of them achieved PR (all confirmed), eleven of them achieved SD and only one patient developed to disease progression. The objective response rate was 60.0 % while the disease control rate was 96.7 %. The most common Grade 3 adverse events were decreased platelet count (20 %), hypertriglyceridemia (10 %) and oral mucositis (6.67 %). 3 patients showed Grade 4 decrease of platelet count (10 %), and both of them belong to the gemcitabine group.
Conclusion
The combination of anlotinib and chemotherapy showed the potential effect and a manageable safety profile in patients with previously untreated EGFR/ALK/ROS1 negative advanced NSCLC.
Table 1: Response rates
Response
Assessed
CR
0
PR
18/30（60.0%）
SD
11/30（36.7%）
PD
1/30 （3.3%）
ORR, n/N（%）
18/30 （60.0%）
DCR, n/N（%）
29/30 （96.7%）
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P2.03 - Biology (ID 162)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Biology
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.03-49 - Roles of CENPU in Lung Adenocarcinoma Progression and Invasion (Now Available) (ID 1382)
10:15 - 18:15 | Author(s): Huimin Wang
- Abstract
Background
Centromere protein U (CENPU), a centromere protein mediating kinetochore-microtubule interaction, is critical for proper cell cycle and mitosis. It has been implicated that CENPU promotes tumorigenesis in variant malignancies. However, roles of CENPU in lung adenocarcinoma progression and underlying mechanisms remain to be elucidated.
Method
CENPU expression in 90 pair lung adenocarcinoma/adjacent normal lung samples was examined with immunohistochemistry (IHC). Then CENPU expression was inhibited with lentiviral-mediated shRNA strategy in human lung adenocarcinoma cell line H1299 to examine the impact of CENPU knockdown for lung adenocarcinoma progression and metastasis. Cell proliferation, colony formation, cell cycle and cell survival were analyzed by Cellomics cell counting method, colonogenesis assay, PI and Annexin V-APC staining respectively while cellular migration and invasion were determined by cell scratch and transwell test. Furthermore, expression of critical factors involved in epithelial-to-mesenchymal transition (EMT) were determined with western blot.
Result
CENPU expression was significantly increased in lung adenocarcinomas as compared to adjacent normal lung tissues (fold change=8.54, P<0.0001) (Fig. 1A). Functionl analysis revealed that in human lung adenocarcinoma cell line H1299, CENPU knockdown impaired cell proliferation (Fig. 1B), inhibited colony formation ability (Fig. 1C) and induced cell cycle arrest (Fig. 1D). Additionally, cellular migration and invasion was also inhibited by CENPU knockdown (Fig. 1E-F). It is further shown that E-Cadherin was induced while N-Cadherin and vimentin were inhibited by CENPU knockdown (Fig. 1G), indicating that CENPU was important for EMT process and cancer metastasis.
Conclusion
It showed that CENPU expression is significantly upregulated lung adenocarcinoma tissue. Functional analysis indicated that CENPU is critical for cell proliferation, survival, migration and metastasis in lung adenocarcinoma cell line H1299. CENPU represents a promising target for lung adenocarcinoma therapy.
