Effect of Wnt signaling suppression on gefitinib in non small cell lung cancer cell lines / 中华病理学杂志

<p><b>OBJECTIVE</b>To explore the effect of Wnt signaling suppression on proliferation of non small cell lung cancer to gefitinib, and its related mechanisms.</p><p><b>METHODS</b>PC9 and PC9/AB2 cells of both gefitinib sensitive and resistant were treated with different concentrations of gefitinib, and the proliferation index was measured using CCK8 kit. The members of Wnt signaling pathway were detected by Western blot. Dual luciferase reportor gene assay (TOP Flash) was used to document the transcriptional level of β-catenin. β-catenin siRNA was transfected into PC9/AB2 cells to suppress the Wnt signaling transcription, followed by treatment with different concentrations of gefitinib. Western blot was then used to detect the expression of EGFR and its downstream signaling after inhibit the expression of β-catenin.</p><p><b>RESULTS</b>Treating with different concentrations of gefitinib, the resistance of PC9/AB2 cells to gefitinib was significantly increased (P < 0.05). The members of Wnt signaling expressed at higher level in PC9/AB2 cells than in PC9 cells (t = 24.590, P = 0.000). TOP Flash examination showed that the endogenous transcriptional activity of Wnt signaling was higher in PC9/AB2 cell than that in PC9 cell (t = 4.983, P = 0.008). Compared with the negative control group, apoptotic rate and sensitivity to gefitinib significantly increased in interfered group (P < 0.05). The expression of p-ERK1/2 significantly decreased after Wnt signaling suppression, although other proteins showed no significant alterations.</p><p><b>CONCLUSION</b>Suppressing the activity of Wnt signaling can partly reverse the celluar resistance to gefitinib in non small cell lung cancer.</p>

Serum cytokine levels in patients with advanced non-small cell lung cancer: correlation with clinical outcome of erlotinib treatment / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Serum expression of cytokines may provide information about the clinical outcome of advanced non-small cell lung cancer (NSCLC) patients. This study aimed to investigate the relationship between serum cytokine levels and the clinical outcome of erlotinib treatment in a second or third line setting in patients with advanced NSCLC.</p><p><b>METHODS</b>A total of 162 patients with advanced NSCLC who received erlotinib as either second or third line therapy were enrolled in this study. Blood samples were collected before the initiation of erlotinib treatment, and the levels of IL-1, IL- 2R, IL-6, and tumor necrosis factor (TNF)-α were assessed by enzyme-linked immunosorbent assay (ELISA). Cutoff points were defined as the median levels of IL-1 (low (≥26.5 pg/ml) and high (>26.5 pg/ml)), IL-2R (low ( = 115 pmol/L) and high (>15 pmol/L)), IL-6 (low (≤49.5 pg/ml) and high (>49.5 pg/ml)), and TNF-α (low (≤48.5 pg/ml) and high (>48.5 pg/ml)). Kaplan-Meier analysis was used to estimate the survival time, and Cox regression analyses were used to correlate cytokines and baseline clinical characteristics with clinical outcomes, including time to progression (TTP) and overall survival (OS).</p><p><b>RESULTS</b>Between January 2007 and May 2011, 162 patients were enrolled. Their median age was 58 years. In this group, 109 were males and 53 were females, 74 were former or current smokers and 88 were non-smokers. A total of 122 patients had adenocarcinoma, 27 had squamous cell carcinoma, and 13 had tumors with other types of histology. And 139 patients had an Eastern cooperative oncology group (ECOG) performance status of 0-1, while 23 scored at 2-3. Expression of IL-1, IL-2R, and IL-6 was not significantly associated with age, gender, ECOG performance status, smoking status, or histology and stage of tumor. Only TNF-α was associated with smoking status (P = 0.045). Survival analysis showed that patients with low levels of either IL-6 or TNF-α had a statistically longer TTP and OS than patients with high expression (P < 0.05). These cytokines remained significant upon multivariate analysis (P < 0.05).</p><p><b>CONCLUSION</b>IL-6 or TNF-α may serve as potential predictive biomarker for the efficacy of erlotinib.</p>

Impact of erlotinib treatment on symptoms and quality of life in patients with advanced non-small-cell lung cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the impact of erlotinib as a second or third line treatment on the symptoms and quality of life (QOL) in patients with advanced non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>Fifty patients with stage III b and IV NSCLC, treated previously with at least one regimen of platinum-based chemotherapy, received 150 mg of erlotinib orally, once a day till disease progression. QOL was assessed by European Organization for Research and Treatment of Cancer QLQ-C30 and the lung cancer module (QLQ-LC13). The primary end points for QOL analysis were time to deterioration of three common lung cancer symptoms: cough, dyspnea and pain.</p><p><b>RESULTS</b>Among 47 evaluable cases, there were partial remission (PR) in 18 cases, stable disease (SD) in 21 cases, and progressive disease (PD) in 8 cases. After two cycles of treatment, the mean scores of global QOL and all 5 functioning scales except the cognitive function increased significantly (P < 0.05). Mean scores of major general symptoms, hypodynamia and anorexia, and disease-related symptoms alleviated significantly. Both response rates of five functioning and global QOL were more than 44% after erlotinib treatment. Response rates of major general symptoms and disease-related symptoms varied from 14% to 76%. Patients with complete or partial response likely had improvement in the QOL response (P < 0.05), and the time to major symptom deterioration in those were significantly longer (P < 0.001) than that in patients with stable or even progressive disease.</p><p><b>CONCLUSION</b>Erlotinib is effective to improve not only survival, but also tumor-related symptoms and quality of life in patients with advanced NSCLC previously treated with cisplatin-contained regimens. The improvement in the quality of life is positively correlated with objective tumor response.</p>

The efficiency and safety analysis of ibandronate at the initial loading dose for metastatic bone pain induced by non-small cell lung cancer / 肿瘤

Objective: To evaluate the efficiency and safety of ibandronate at the initial loading dose in the treatment of metastatic bone pain (MBP) induced by non-small cell lung cancer (NSCLC). Methods: Thirty cases of NSCLC patients who were admitted to our hospital from May 2006 to July 2007 were retrospectively analyzed. They received loading dose of ibandronate for MBP treatment. Ibandronate was given to the patients intravenously at initial loading dose of 6 mg for more than 15 min on 3 consecutive days. Then ibandronate was administered repeatedly at 6 mg every 3 to 4 months. The response time, pain score, QOL score, daily morphine consumption dose were recorded. The serum markers such as calcium, creatinine, alkaline phosphatase (AKP) were monitored. Results: Twenty nine cases were eligible to evaluate the efficiency and safety. Among them, the MBP of 25 cases (86.2%) were relieved. Their average response time was 2.9 ± 0.8 days. The pain score was significantly decreased after treatment and the life qualities of patients were markedly improved (P <0.001). The morphine consumption dose was reduced by about 20 to 40 mg in 4 cases after treatment. The serum calcium level increased in 7 patients before treatment and declined to the normal level after treatment. The adverse reaction was relieved after treatment and no renal toxicity was observed. Conclusion: Administration of ibandronate at initial loading dose had quick on-set and mild side effects. It could significantly relieve metastasis bone pain and improve QOL, reduce the morphine consumption dose and avoid morphine-induced adverse reaction, and effectively decrease serum calcium level. Administration of ibandronate at initial loading dose is a new promising option for treatment of the MBP in NSCLC.