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H. Tang
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P1.01 - Advanced NSCLC (ID 757)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.01-017 - ALK-Rearranged May Promote VTE by Increasing the Expression of TF in Advanced Lung Adenocarcinoma (ID 9778)
09:30 - 09:30 | Author(s): H. Tang
- Abstract
Background:
Patients with lung cancer are at increased risk for venous thromboembolism (VTE).About 8% to 15% of patients with advanced none small-cell lung cancer(NSCLC) experience a VTE in the course of their disease. However, the incidences of VTE in different molecular subtypes of NSCLC are rarely reported though they have big differentiation in clinical feature and therapeutic effect.Tissue Factor (TF) expressed in many solid tumors could bind and activate coagulation factor FVII and trigger the downstream coagulation cascade leading to thrombin generation and clot formation.
Method:
Here we extracted retrospective data from electronic medical records at Henan Cancer Hospital in China between January 2015 and January 2016. Lung adenocarcinomas with ALK-rearranged, EGFR mutation and both negative were classified. The incidence rate of VTE after diagnosed with lung adenocarcinoma was calculated and analyzed. Then we randomly selected ALK-rearranged and ALK-rearranged negative lung adenocarcinoma tissues and detected TF expression in them with imunohistochemistry.
Result:
At a median follow-up of 19 months, 5.85% (30 in 513) patients with advanced lung adenocarcinoma experienced VTE. Patients with different molecular subtypes put up different rate of VTE (P=0.0021). Among them ALK-rearranged were more likely to experience VTE (6 in 29, 20.69%). EGFR and both negative had lower rate of VTE and had no big difference between them (11 in 218, 5.05%; 13 in 266, 4.89% respectively).The expression of TF performed similar feature. TF high expression in ALK-rearranged tissues is 41.67% (10 in 24) dramatically higher than that in ALK-rearranged negative tissues (11.54%, 3 in 26, P=0.0152).
Conclusion:
The rate of VTE in ALK-rearranged advanced lung adenocarcinoma cohorts was about 4 fold higher than that in EGFR mutation and both negative patients. ALK-rearranged may promote that by increasing TF expression. The mechanism warrants further research.
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P1.15 - SCLC/Neuroendocrine Tumors (ID 701)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: SCLC/Neuroendocrine Tumors
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.15-006 - Enriched Environment and Anti-Depressants Enhance Platinum Chemosensitivity of Small Cell Lung Cancer (ID 7377)
09:30 - 09:30 | Author(s): H. Tang
- Abstract
Background:
Small cell lung cancer (SCLC) is one of the most lethal malignancies with rapid chemoresistance. Based on our previous study, enriched environment (EE) has a clear effect on improving the mental state of mice and can reduce chemoresistance caused by platinum regimens. In this study we investigated the complex links between benign mental stress (EE) and chemosensitivity of SCLC, and use anti-depressants to improve the mental state of mice to observe its impact on chemosensitivity to platinum regimens, and the underlying mechanism was explored.
Method:
The mental state of mice was evaluation by behavior tests include: elevated plus maze (EPM), open field experiment (OF), forced swimming (FS). Then, the mice were transplanted subcutaneously and treated with cisplatin, carboplatin and oxaliplatin. The tumor was analyzed by gene expression profiling and the differential genes were screened. The expression level of differential genes were examed by real-time PCR, and verified by western bolt and immunohistochemistry, respectively. And then ABCG2 blocker was used for chemosensitivity verification in vivo and in vitro.
Result:
EE significantly increased the movement on openarms in the EPM (35.24 sec V.S. 16.78 sec, P<0.01), increased the center area time in OF test (54.25 sec V.S. 35.24 sec, P<0.05), significantly increased the struggling time in the FS test (46.02 sec V.S. 25.81 sec, P<0.01). Antidepressants can also significantly improve the state of depression of mice, but can not achieve the effect of EE. For platinum chemosensitivity test, the antidepressant drugs (Diazepam, Quetiapine and Clomipramine) have no direct inhibition to tumor cells. A can significantly increased the sensitivity of chemotherapy in mice, but can not achieve the inhibitory effect of EE. Next we found the serum BDNF levels significantly decreased in EE mice. Similarly, antidepressants also significantly reduced serum BDNF levels in mice. Gene expression profiles showed that a variety of genes were downregulated mainly in ABC transporters and drug metabolic pathways by EE and antidepressants. The expression level of ABCB1, ABCC2, ABCG2, ABCC9, PPARa, DPYD, GST-P1 and GSTM1 in SCLC sample were examed by real-time PCR, and verified by western bolt and immunohistochemistry, respectively. ABCG2 expression in tumor of EE and antidepressants mice were even 3 fold higher than control (P<0.001). Nicardipine blocks ABCG2 expression can restore chemosensitivity to platinum based drugs (P<0.001).
Conclusion:
Antidepressants can partially mimic the chemotherapeutic effect of EE and we confirm that the mechanism is partially achieved by increasing BDNF and reducing the expression of ABCG2.
