Neoadjuvant therapy affects tumor growth markers in early stage non-small-cell lung cancer

Chorostowska-Wynimko J, Zaleska J, Chabowski M, Szpechcinski A, Zych J, Rudzinski P, Langfort R, Orlowski T, Roszkowski-Sliz, Roszkowski-Sliz K

Description

While adjuvant therapy of early-stage non-small-cell lung cancer (NSCLC) is widely accepted, literature data concerning neoadjuvant treatment provide contradictory results with both improved and unaffected survival rates. Also, data concerning potential effects of neo-adjuvant therapy on cellular level are scarce. Objective The aim of present study was to analyze the effect of chemotherapy followed by surgical resection on several key biological markers of tumor growth (TGF-β, VEGF), apoptosis (sAPO-1/Fas/CD95) and invasiveness (TIMP-1) assessed in the sera of NSCLC early-stage patients (IB-IIIA). Materials and methods Measurements were performed by ELISA method in blood serum from 24 NSCLC patients (I-IIIA) collected prior therapy, one day before surgery and 3 days after. Results TGF-β serum concentrations were significantly lower after both chemotherapy (P < 0.05) and surgery (P < 0.01) in comparison to the baseline. VEGF levels decreased following NEO therapy with subsequent significant up-regulation after surgery (P < 0.001). Interestingly, post-surgery serum VEGF strongly correlated with TGF-β concentration (r = 0.52, P = 0.014). No significant differences were observed for serum sAPO-1/CD95/FAS as well as TIMP-1 concentrations at any of three evaluated time-points. Conclusion Neoadjuvant treatment of early-stage NSCLC affects mostly mechanisms responsible for tumor growth and vascularization. Its effect on cancer cells apoptotic activity needs further evaluation.

Sujets

• Lung cancer
• Neoadjuvant therapy
• Vascular endothelial growth factor

Informations

• Publié par: biomed
• Publié le: 01 janvier 2009
• Nombre de lectures: 7
• Langue: English

Extrait

42

Eur J Med Res (2009) 14(Suppl. IV): 42-44

EUROPEAN JOURNAL OF MEDICAL RESEARCH

December 7, 2009

© I. Holzapfel Publishers 2009

N EOADJUVANT T HERAPY A FFECTS T UMOR G ROWTH M ARKERS IN E ARLY S TAGE N ON -S MALL -C ELL L UNG C ANCER

1 23 12 3 J. Chorostowska-Wynimko , J. Zaleska , M. Chabowski , A. Szpechcinski , J. Zych , P. Rudzinski , 4 32 R. Langfort , T. Orlowski , K. Roszkowski-Sliz

1 23 Laboratory ofMolecular Diagnostics and Immunology,Third Department ofLung Diseases,Department ofThoracic Surgery, and 4 Department ofPathology, National Institute ofTuberculosis and Lung Diseases, Warsaw, Poland

Abstract Intr oduction:early-stageWhile adjuvant therapy of non-small-cell lung cancer (NSCLC) is widely accept- ed, literature data concerning neoadjuvant treatment provide contradictory results with both improved and unaffected survival rates. Also, data concerning poten- tial effects ofneo-adjuvant therapy on cellular level are scarce. Objective:present study was to analyze theThe aim of effect ofchemotherapy followed by surgical resection on several key biological markers oftumor growth (TGF-β, VEGF), apoptosis (sAPO-1/Fas/CD95) and invasiveness (TIMP-1) assessed in the sera ofNSCLC early-stage patients (IB-IIIA). Material and methods:Measurements were performed by ELISA method in blood serum from 24 NSCLC patients (I-IIIA) collected prior therapy, one day be- fore surgery and 3 days after. Results:TGF-βserum concentrations were significant- ly lower after both chemotherapy (P<0.05) and surgery (P<0.01) in comparison to the baseline. VEGF levels decreased following NEO therapy with subsequent sig- nificant up-regulation after surgery (P<0.001). Interest- ingly, post-surgery serum VEGF strongly correlated with TGF-βconcentration (r = 0.52, P = 0.014). No significant differences were observed for serum sAPO- 1/CD95/FAS as well as TIMP-1 concentrations at any of threeevaluated time-points. Conclusion:early-stageNeoadjuvant treatment of NSCLC affects mostly mechanisms responsible for tu- mor growth and vascularization. Its effect on cancer cells apoptotic activity needs further evaluation. Key words:lung cancer, neoadjuvant therapy, TGF-β, VEGF, sAPO-1, TIMP-1 I NTRODUCTION Lung cancer is recognized as the leading cause ofcan- cer-related deaths with more than 1 200 000 cases per year worldwide. High mortality rates with less than 10% ofpatients surviving their malignancy are attrib- uted both to delayed diagnosis (70% in stage IIIB and IV) and consequently less than satisfactory treatment effectiveness. Thus, new strategies in lung cancer ther- apy have been introduced in recent years, promising

better outcomes in certain patient groups.While adju- vant, post-surgery, therapy ofearly- stage non-small- cell lung cancer (NSCLC) is now widely accepted, lit- erature data concerning neoadjuvant, pre-surgery, treatment (NEO) provide contradictory results with both improved or unaffected survival rates [1]. A mul- ticenter study ofthe French Thoracic Cooperative Group with 355 NSCLC patients demonstrated longer 2-year overall survival rate in patients on neo-adjuvant treatment (59% vs. 52%) with particular benefit in ear- ly-stage disease (N0-N1) [2]. On the other hand, American Intergroup (S9900) with 354 patients showed no significant benefit ofthat strategy [3]. Im- portantly enough, data concerning potential effects of neo-adjuvant therapy on the cellular or molecular lev- els are scarce. Therefore, the aim ofpresent study was to analyze the effect ofchemotherapy followed by surgical resection on several key biological markers of tumor growth (TGF-β, VEGF), apoptosis (sAPO- 1/Fas/CD95) and invasiveness (TIMP-1) assessed in the sera ofNSCLC early-stage patients (IB-IIIA). M ATERIAL AND M ETHODS S TUDY D ESIGN

The study was approved by a local Ethics Committee and informed consent was obtained from all partici- pating subjects. The study group consisted of24 patients (22-male; 2-female), mean age 62 ±21 years, with diagnosed ear- ly stage NSCLC (IA-1, IB-1, IIA-1, IIB-9, IIIA-12). Neoadjuvant treatment (cisplatin and vinarelbin) was administered prior to radical surgery in all patients. Blood samples were collected prior therapy, one day before surgery and 3 days after. Serum was separated by centrifugation, aliquoted and frozen at -70°C. Tu- mor and normal tissue samples obtained during sur- gery were immediately processed: sonicated on ice and centrifuged. Supernatants were aliquoted and frozen at -70°C.

C YTOKINE A SSESSMENT

Cytokines measurements in serum and tissues were performed by quantitative enzyme immunoassay tech-