The resistance of non-small cell lung cancer (NSCLC) to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) has been brought into focus. COX-2 signal pathway was found to be closely related to EGFR signal pathway by recent researches, and there has been a growing interest to focus the researches on whether COX-2 pathway inhibition improves the efficacy of EGFR-TKIs in treating advanced NSCLC. In this review, we will illustrate recent advances of combined inhibition of EGFR and COX-2 signal pathways in NSCLC therapy.
ObjectiveTo explore the relationship of the clinicopathological characteristics of non-small cell lung cancer (NSCLC) with the mutations of epidermal growth factor receptor (EGFR), K-ras and EML4-ALK fusion gene in cell blocks of pleural effusion (PLE). MethodsA total of 268 cytological specimens of PLE (pleural effusion), from Central Hospital of Zibo city were collected from advanced NSCLC patients between January 2012 year and June 2014 year. There were 165 male and 103 female patients at age of 53.6 (31-76) years. Qualitative diagnosis has been made in the 268 patients using PLE samples with conventional smear. Immunohistochemical staining combined with cell block section were used for further classification. There were 76 patients diagnosed as NSCLC with 39 patients of adenocarcinoma and 37 patients of squamous-cell carcinoma. In the 76 patients of lung biopsy specimens and PLE, EGFR and K-ras mutations, EML4-ALK fusions were tested. ResultsEGFR mutations rate was 34.21% (26/76). K-ras mutations rate was 6.58% (5/76). EML4-ALK fusions rate was 7.89% (6/76) at the same time. EGFR and K-ras mutations, EML4-ALK fusions were mostly found in young female adenocarcinoma patients who were non-smokers. EGFR and K-ras mutations or EML4-ALK fusions were not found in the same patient. ConclusionCytological specimens are feasible for detecting EGFR were K-ras mutations and EML4-ALK fusions. This will especially benefit to patients whose histological specimen can not be obtained.
ObjectiveTo reveal the true value of plasma detection of epidermal growth factor receptor (EGFR) mutation for early-stage non-small cell lung cancer (NSCLC) gene diagnosis and to predict survival prognosis. MethodsTissue samples of positive EGFR mutations by using amplification refractory mutation system (ARMS) method were surgically resected from 198 patients with stage I-IV NSCLC between February 2014 and June 2015 in Tangdu hospital. Paired blood samples were collected before surgery. And the cellfree DNA (cfDNA) in plasma was extracted, plasma EGFR mutations were detected by real-time polymerase chain reaction (PCR). Concentration of cfDNA was measured by ultraviolet spectrophotometry. Follow-up observation for stage ⅢA patients was put into force after surgery. Kaplan-Meire was used in survival analysis. ResultsThe sensitivity of EGFR mutation for the 198 paired tissues and plasma samples was 17.2%.The sensitivity was positively correlated with TNM stage and negatively correlated with tumor differentiation. The sensitivity of sage ⅢA was 33.3%, significantly higher than that of the patients at stage ⅠA (1.6%, P=0.000) and stage ⅠB (7.9%, P=0.004). The sensitivity of poor differentiation was 36.8%, significantly higher than that of high differentiation (0.0%, P=0.000) and moderate differentiation (15.7%, P=0.010). There was no correlation between plasma cfDNA concentration and patient characteristics. Survival analysis showed that plasma detection was a vital factor for predicting postoperative survival prognosis of stage ⅢA patients (P=0.014). ConclusionTissue samples cannot be replaced by plasma samples for epidermal growth factor receptor (EGFR) mutation test in early-stage NSCLC patients, currently. When the sensitivity increases dramatically in the plasma samples of stage ⅢA NSCLC and poor differentiation tumor, we recommend using plasma detection for gene diagnosis, dynamic monitoring of EGFR mutations in stage ⅢA or poorly differentiated tumors, especially in NSCLC patients whose tissue samples cannot be obtained by surgery. And plasma EGFR detection is a valuable method of forecasting survival prognosis for locally advanced NSCLC patients.
Objective To compare the long-term cost-utility of three first-generation EGFR-TKIs targeted drugs, gefitinib, icotinib, and erlotinib as first-line treatments for advanced non-small cell lung cancer (NSCLC). Methods Real-world data were collected from 1 511 patients with advanced NSCLC treated with first-generation EGFR-TKIs as first-line treatment at West China Hospital of Sichuan University from 2009 to 2019. A three-state Markov model was established to evaluate the clinical efficacy, safety and cost-utility of three first-generation EGFR-TKIs targeted drugs. The transition probability of each state was obtained by survival analysis, the direct and indirect costs were calculated by the bottom-up method, the health utility value was obtained through literature research, the incremental cost effectiveness ratio (ICER) and quality-adjusted life years (QALYs) were calculated, and sensitivity analyses and Monte Carlo simulations were performed. Results There was no significant difference in clinical efficacy among the three first-generation EGFR-TKIs in the treatment of NSCLC. The incidence of skin rash and liver injury caused by gefitinib was significantly higher than that caused by icotinib and erlotinib (P<0.05). The average economic burden of patients treated with icotinib was the lowest (CNY 192 535.3) (P<0.01). The cost-utility ratio of icotinib (CNY 132 985.9/QALYs) was much lower than that of gefitinib (CNY 205 005.3/QALYs) and erlotinib (CNY 172 893.1/QALYs). Conclusion Compared with the three first-generation EGFR-TKIs drugs, icotinib is the most cost-effective.
目的:探讨PLGA材料构建的纳米粒载体导入表皮生长因子受体(EGFR)反义寡核苷酸在头颈鳞癌基因治疗中的可行性,为头颈肿瘤基因治疗中载体的选择提供一个新的研究思路。方法:以PLGA为材料,采用油包水双乳化溶剂蒸发法制备载EGFR正义、反义寡核苷酸纳米颗粒;纳米颗粒转染SCCⅦ细胞株;MTT法了解纳米颗粒对细胞的毒性;通过实时荧光定量PCR检测转染后EGFR基因mRNA表达水平。结果:获得了制备载寡核苷酸PLGA纳米颗粒工艺流程,PLGA纳米颗粒平均粒径116nm±7.57nm。纳米颗粒体外转染SCCⅦ细胞,MTT结果显示纳米颗粒对细胞生长无明显抑制效应,同时具有明显抑制EGFR基因mRNA表达效应。结论:PLGA纳米颗粒可以有效地载入反义寡核苷酸,达到抑制靶基因的效果,同时无明显的细胞毒性。
ObjectiveTo explore the expression of vascular endothelial growth factor receptor-2(VEGFR-2) protein in esophageal squamous cell carcinoma (ESCC) and to analyze the relationship between VEGFR-2 and prognostic of esophageal cancer in Uygur of Xinjiang. MethodsThe expression of VEGFR-2 protein including 72 patients with ESCC[with 56 males and 16 females at age of 57 (43-79) years] and paracarcinomatous tissues of 28 patients were detected by immunohistochemistry staining (SP) between January 2007 and september 2009 in this hospital. The Kaplan-Meier and Cox proportional hazards analysis were used to analyze the prognosis of ESCC. ResultsThe positive expression rate of VEGFR-2 protein in 72 patients with ESCC was 80.56% (58/72) and 0 in paracarcinomatous tissues. The expression of VEGFR-2 protein in the ESCC was much higher than that in paracarcinomatous tissues with a statistical difference (P<0.05). The expression of VEGFR-2 protein was significantly correlated with depth of invasion, lymph node metastasis, distant metastasis and TNM staging (P<0.05). Tumor size was no correlation with expression of VEGFR-2 protein (P>0.05). Kaplan-Meier survival analysis indicated that five-year survival rate in positive expression of VEGFR-2 was higher than that in the negative group. Lymph node metastasis, TNM staging, and the positive expression of VEGFR-2 protein were independent prognostic factors. ConclusionVEGFR-2 protein is expressed more in ESCC and might be used as the index to predict prognosis and metastasis of esophagedal carcinoma in Uygur.
ObjectiveTo systematically evaluate the efficacy and safety of epidermal growth factor receptortyrosine kinase inhibitors (EGFR-TKIs) as the first-line treatment for patients with advanced non-small cell lung cancer (NSCLC). MethodDatabases including PubMed, EMbase, The Cochrane Library (Issue 1, 2015) , CBM, CNKI, VIP and WanFang Data were electronically searched from inception to March 2015, to collect randomized controlled trials (RCTs) about EGFR-TKIs versus chemotherapy for advanced NSCLC patients. Two reviewers independently screened literature, extracted data, and assessed the risk of bias of included studies. Then, meta-analysis was performed by RevMan 5.2 software. ResultsA total of 9 RCTs involving 3 841 patients were included. The results of meta-analysis showed that: for patients with EGFR mutation-positive, the rate of progression-free survival (PFS) (HR=0.41, 95%CI 0.31 to 0.54, P<0.000 01) , objective response rate (ORR) (RR=2.23, 95% CI 1.73 to 2.87, P<0.000 01) and quality of life (QoL) in the EGFR-TKI group were superior to the chemotherapy group; There was no statistical difference between two groups in rate of overall survival (OS) (HR=1.04, 95% CI 0.88 to 1.24, P=0.62) . The incidences of diarrhea (RR=3.81, 95% CI 2.15 to 6.76, P<0.001) and rash (RR=8.14, 95% CI 3.55 to 18.68, P<0.001) were significantly higher, but the incidence of blood toxicity was lower in the EGFR-TKI group that those in the chemotherapy group. ConclusionsCurrent evidence shows EGFR-TKI is superior to chemotherapy for advanced NSCLC patients with EGFR mutation-positive. However, due to the limited quantity and quality of the included studies, more high-quality studies are needed to verify the above conclusion.
Objective To analyze the relationship between the epidermal growth factor receptor(EGFR) gene mutation and malignant pulmonary focal ground-glass lesion (fGGL). Methods We retrospectively collected the clinical data of 86 patients with surgical treatment in the department of cardiothoracic surgery of Changzheng Hospital from August 2012 to February 2015. There were 26 males and 60 females with a mean age of 56.14±10.55 years. We analyzed the relationship between the EGFR gene mutation and the related clinical data. Results Postoperative pathology showed atypical adenomatous hyperplasia (AAH) combined with focal adenocarcinoma in situ (AIS) or AIS in 10 patients, minimally invasive adenocarcinoma (MIA) in 15, and lepidic predominant adenocarcinoma (LPA) in 61. The EGFR gene mutation reports showed the exon 19 19-del mutation in 14 patients, exon 21 L858R mutation in 27, and exon 21 L861Q mutation in 2. There was no difference between the mutation of EGFR gene and clinical factors except age and smoking (P>0.05). Till June 30, 2015, all patients were alive and follow-up was 440.48±186.61 days. Conclusion The EGFR gene in patients with malignant pulmonary fGGL shows a higher mutation rate, which provides important clinical reference data for the basic research and the clinical treatment.