02.12.2016 Views

Journal Thoracic Oncology

WCLC2016-Abstract-Book_vF-WEB_revNov17-1

WCLC2016-Abstract-Book_vF-WEB_revNov17-1

SHOW MORE
SHOW LESS

Create successful ePaper yourself

Turn your PDF publications into a flip-book with our unique Google optimized e-Paper software.

Abstracts <strong>Journal</strong> of <strong>Thoracic</strong> <strong>Oncology</strong> • Volume 12 Issue S1 January 2017<br />

complete resection. Methods: We retrospectively reviewed the medical<br />

records of treatment-naïve patients who underwent complete resection of<br />

stage I lung adenocarcinoma between January 2008 and December 2014.<br />

Mutation testing was performed on resected tumor using multiplex (SNaP<br />

Shot) polymerase chain reaction assay. Survival curves were generated with<br />

Kaplan-Meier method and compared using a log-rank test. A Cox proportional<br />

hazards model was used for multivariate analysis. Results: Of 583 patients,<br />

127 (21.8%) patients had EGFR-mutations. Median follow up period after<br />

surgery was 36.9 months (range: 0.1-95.8). Patients with EGFR mutations<br />

showed a better 5-year recurrence-free survival (RFS, 89.4% vs 77.8%,<br />

p=0.0053) and 5-year overall survival (OS, 99.1% vs 87.7%, p=0.0044) than<br />

those with EGFR wild-type (Figure). Multivariate analysis demonstrated that<br />

the presence of EGFR mutation (HR=0.4875, p=0.0388) and pathological stage<br />

0 or IA (HR=0.4590, p=0.0016) were independent prognostic factors for better<br />

RFS. The presence of EGFR mutations (HR=0.1878, p=0.0443), lobar resection<br />

(HR=0.4076, p=0.0123), and ECOG performance status 0 (HR=0.4061,<br />

p=0.0259) were independent prognostic factors for better OS.<br />

known as Cancer Stem Cells (CSCs), which are able to grow as spheroids<br />

(suspension culture). The aim of the study was to obtain tumorspheres<br />

from lung cancer cell lines and to use them as an in vitro platform for drug<br />

screening. Methods: Cells from lung cancer cell lines (A549, H1650, PC9, H460<br />

and H358) were grown in monolayer and as spheroids. Cultured cells were<br />

used: (i) to compare the cytotoxic effect of anticancer drugs in adherent<br />

vs lung-tumorspheres (ii) to perform a high-throughput screening with a<br />

commercial chemical library (Prestwick) and (iii) to analyze the citotoxicity<br />

of specific inhibitors of Wnt, Hedgehog and Notch pathways. Briefly, cells<br />

were plated at the desired density in 200 μl of medium in 96-well plates and<br />

compounds were added at 4 different concentrations (n=3). Cell viability was<br />

measured after 48 and 72h, using MTS Assay. Cell viability was normalized<br />

to the respective mock-treated control cells and presented as percentage of<br />

control. Results: Cells cultured in serum-free conditions were able to form<br />

spheroids, such as stem-like cells. Under these culture conditions, classical<br />

anticancer drugs (cisplatin, paclitaxel, vinorelbine and pemetrexed) exhibited<br />

mild or null cytotoxic effects on A549, H1650, PC9, H460 and H358 spheroids.<br />

Moreover, we performed a high-throughput screening with Prestwick library<br />

and remarkably, three compounds reduced the number of viable cancer cells.<br />

As regards ‘stemness’ inhibitors, Wnt (IWP2 and XAV939) and Hedgehog<br />

inhibitors (Vismodegib) show high activity against tumorspheres (p

Hooray! Your file is uploaded and ready to be published.

Saved successfully!

Ooh no, something went wrong!