Nab-paclitaxel(abraxane)-based chemotherapy to treat elderly patients with advanced non-small-cell lung cancer:a single center,randomized and open-label clinical trial

Background： The purpose of this study is to evaluate the clinical efficacy and safety of abraxane-based chemotherapy with/without nedaplatin in elderly patients with non-small-cell lung cancer （NSCLC）. Materials and methods： From October 2009 to January 2013, 48 elderly patients （≥65 years） with NSCLC were investigated in this clinical trial. The patients were randomized and equally allocated into arms A and AP- （A） abraxane （130 mg/m2, days 1, 8）; （B） abraxane ＋ nedaplatin （20 mg/m2 days 1-3, q3w）. The parameters of objective response rate （ORR）, disease control rate （DCR）, progression-free survival （PFS）, overall survival （OS） and side effects were evaluated between two arms. Results： Over 80% of the patients completed four cycles of chemotherapy. The total ORR was 21.3 %, DCR was 55.3%, PFS 4.5 months and OS 12.6 months. No significant difference was found between arms A and AP in terms of ORR （16.7% vs. 26.1%, P=0.665） or DCR （55.3% vs. 56.5%, P=0.871）. The median PFS in arm A was 3.3 months [25-75% confidence interval （CI）： 3.1-7.2] and 5.5 months （25-75% CI： 3.2-7.0） in arm AP with no statistical significance （P=0.640）. The median OS in arm A was 12.6 months （25-75% CI： 5.7-26.2） and 15.1 months （25-75% CI： 6.4-35.3） in arm AP with no statistical significance （P=0.770）. The side effects were mainly grade 1-2. The incidence of grade 3-4 toxicities was 29.1% in arm A and 62.5% in arm AP with a statistical significance （P=0.020）. Conclusions： Compared with combined therapy, abraxane alone chemotherapy was beneficial for elderly NSCLC patients with better tolerability and less adverse events, whereas did not significantly differ in terms of ORR, DCR, PFS or OS.

Weekly albumin-bound paclitaxel/cisplatin versus gemcitabine/cisplatin as first-line therapy for patients with advanced non-small-cell lung cancer:A phase II open-label clinical study

Objective: The aim of this trial was to compare both the efficacy and the safety of a weekly nanoparticle albumin-bound paclitaxel(nab-paclitaxel) plus cisplatin vs. gemcitabine plus cisplatin in patients with advanced non-small-cell lung cancer(NSCLC).Methods: A total of 84 participants received either 100 mg/m^2 nab-paclitaxel each week on d 1, 8 and 15 of a 28 day cycle, as well as cisplatin 75 mg/m^2 on d 1 every three weeks(nab-TP arm); or gemcitabine 1,000 mg/m^2 on d 1 and 8, plus cisplatin 75 mg/m^2 on d 1 every three weeks(GP arm). The primary end point was progression-free survival(PFS). The secondary end points were overall response rate(ORR) and overall survival(OS).Results: According to our analysis, the median PFS was 4.8 months for the nab-TP arm vs. 5.2 months for the GP arm(P=0.55). Analysis showed the median OS was 14.6 months for participants who were in the nab-TP arm vs. 15.1 months for those in the GP arm(P=0.94). Besides, nab-TP showed OS advantages over GP in patients harboring epidermal growth factor receptor(EGFR) mutation(26.7 vs. 15.3 months, P=0.046) and patients with a performance status of 0(23.5 vs. 14.7 months, P=0.020). It was found that incidences of drug-related grade 3 or 4 toxicities were comparable between the two treatment arms.Conclusions: Therefore, it can be seen that weekly nab-TP treatment has a similar efficacy and tolerability to GP treatment for patients who are undergoing their first-line treatment for NSCLC. It could be that survival differences among platinum doublets in the context of both EGFR mutation and performance status have the potential to be the basis for our further clinical trials.

Sequential therapy according to distinct disease progression patterns in advanced ALK-positive non-small-cell lung cancer after crizotinib treatment

Objective: Crizotinib is recommended as the first-line therapy for advanced anaplastic lymphoma kinase(ALK)-positive non-small-cell lung cancer(NSCLC). Despite its initial efficacy, patients ultimately acquire resistance to crizotinib within 1 year. In such patients, the optimal sequential therapy after crizotinib treatment remains unknown. This study explored which sequential therapy option confers the greatest benefit.Methods: A total of 138 patients with advanced ALK-positive NSCLC resistant to crizotinib were studied. Based on patterns of disease progression of metastases, patients were divided into 3 groups: brain progression, non-liver progression, and liver progression. Sequential therapies included crizotinib continuation plus local therapy, nextgeneration ALK inhibitors(ALKi's), and chemotherapy. The primary endpoint was overall survival(OS) from the time of crizotinib resistance to death or last follow-up.Results: The 138 patients included 64 cases with progression in brain, 57 cases in non-liver sites and 17 cases in liver. A significant difference in OS was observed among the distinct progression pattern(median OS, 25.4 months in brain, 15.8 months in non-liver, and 10.8 months in liver, respectively, P=0.020). The difference in OS among sequential therapies was statistically significant in the non-liver progression group(median OS, 27.6 months with next-generation ALKi's, 13.3 months with crizotinib continuation, and 10.8 months with chemotherapy,respectively, P=0.019). However, crizotinib continuation plus local therapy seems to provide non-inferior median OS compared with next-generation ALKi's for patients with brain progression(median OS, 28.9 months vs.32.8 months, P=0.204). And no significant differences in OS were found in patients with progression in liver(P=0.061).Conclusions: Crizotinib continuation together with local therapy might be a feasible strategy for patients with progression in brain beyond crizotinib resistance, as well as next-generation ALKi's. Next-generation ALKi's tended to provide a survival benefit in patients with non-liver progression.

Advances in adjuvant systemic therapy for non-small-cell lung cancer

Non-small-cell lung cancer remains a leading cause of death around the world. For most cases, the only chance of cure comes from resection for localised disease, however relapse rates remain high following surgery. Data has emerged over recent years regarding the utility of adjuvant chemotherapy for improving disease-free and overall survival of patients following curative resection. This paper reviews the clinical trials that have been conducted in this area along with the studies integrating radiation therapy in the adjuvant setting. The role of prognostic gene signatures are reviewed as well as ongoing clinical trials including those incorporating biological or targeted therapies.

Relevance of EGFR gene mutation with pathological features and prognosis in patients with non-small-cell lung carcinoma

Objective:To study the relevance of EGFR gene mutation with pathological features and prognosis in patients with non-small-cell lung carcinoma.Methods:A total of 297 patients from July 2009 to May 2013 were chosen as objects.EGFR gene mutation were detected with fluorescence quantitative PCR.Relevance of EGFR gene mutation with clinical and pathological features was analyzed,and the prognosis of EGFR- mutant-patients and that of EGFR- wide type-patients was compared.Results:In 297 patients.136(45.79%) showed EGFR gene mutation.EGFR gene mutation had no significant relevance with age.gender,smoking history,family history of cancer and clinical stage(P>0.05);there was significant relevance between EGFR gene mutation and blood type,pathologic types,differentiation and diameter of cancer(P<0.05).The difference between prognosis of EGFR- mutant-patients and that of EGFR- wide type-patients was statistical significance(P<0.05).Conclusions:EGFR gene mutation has significant relevance with pathological features,the prognosis of EGFRmutant-paticnts is better than that of EGFR- wide type-patients.

Review of the current targeted therapies for non-small-cell lung cancer

The last decade has witnessed the development of oncogene-directed targeted therapies that have significantly changed the treatment of non-small-cell lung cancer(NSCLC). In this paper we review the data demonstrating efficacy of gefitinib, erlotinib, and afatinib, which target the epidermal growth factor receptor(EGFR), and crizotinib which targets anaplastic lymphoma kinase(ALK). We discuss the challenge of acquired resistance to these small-molecular tyrosine kinase inhibitors and review promising agents which may overcome resistance, including the EGFR T790 Mtargeted agents CO-1686 and AZD9291, and the ALKtargeted agents ceritinib(LDK378), AP26113, alectinib(CH/RO5424802), and others. Emerging therapies directed against other driver oncogenes in NSCLC including ROS1, HER2, and BRAF are covered as well. The identification of specific molecular targets in a significant fraction of NSCLC has led to the personalized deployment of many effective targeted therapies, with more to come.

Weekly intravenous nanoparticle albumin-bound paclitaxel for elderly patients with stage IV non-small-cell lung cancer:a series of 20 cases

The purpose of this study was to evaluate the efficacy and safety of nanoparticle albumin-bound paclitaxel as a rescue regimen in the treatment of patients with advanced non-small-cell lung cancer. We retrospectively reviewed the medical records of 20 patients with stage IV non-small-cell lung cancer. The patients had progressive disease after standard antitumor therapy and subsequently received intravenous albumin-bound paclitaxel at the dose of 100 mg/m2 in weekly schedule. Cumulative findings showed that the overall response rate was 30.0%, the disease control rate amounted to 40%, and the 1 year survival rate was 30%. In addition, the median time to progression and the median survival time reached 5 and 10 months, respectively. Meanwhile, no severe hypersensitivity reactions and grade 4 adverse effects were reported. In summary, weekly-administered albumin-bound paclitaxel seems to be an effective and safe regimen for elderly patients with stage IV non-small-cell lung cancer who were refractory to conventional therapy.

Inhibitory Effect of MiR-449b on Cancer Cell Growth and Invasion through LGR4 in Non-Small-Cell Lung Carcinoma

Non-small-cell lung carcinoma （NSCLC） is one of the most frequently diagnosed malignancies worldwide. Previous studies have shown that microRNA-449b （miR-449b） functions as a tumor suppressor in many cancers. However, the role of miR- 449b in NSCLC is still unknown. In the present study, miR-449b was significantly down- regulated in NSCLC samples and cell lines. Bioinformatics analysis revealed that 3＇-UTR region of leucine rich repeat containing G protein-coupled receptor 4 （LGR4） mRNA had putative complementary sequences to miR-449b, which was further confirmed by the luciferase assay. Western blotting showed that restoration of miR-449b in NSCLC cells decreased the expression of LGR4. Interestingly, over-expression of miR-449b inhibited growth and invasion of NSCLC cells in vitro. Furthermore, ectopic expression of LGR4 reversed miR-449b-suppressed proliferation and invasion of NSCLC cells. Therefore, the data of the present study demonstrate that miR-449b inhibits tumor cell growth and invasion by targeting LGR4 in NSCLC.

Clinical observation of pemetrexed on advanced non-small-cell lung cancer

我们的学习的目的是观察病人们由 pemetrexed 治疗了的先进非小的房间肺癌症(NSCLC ) 的 50 个盒子的功效和毒性的目的。方法五十个病人包括 29 女性和 21 男性，与中部的年龄 62 年( 3582 年)和左 37 个盒子被对待， pemetrexed 在肿瘤学的部门与铂结合了，到2009年3月的从2006年6月的武汉大学的 Renmin 医院。挑选代理人政体：病人们收到了 pemetrexed 与每 21 天的白天 1 上的 500 mg/m2。联合政体：病人们收到了 pemetrexed 白天 1 上的 500 mg/m2 和 carboplatin 白天 1 上的 300 mg/m2 或 cisplatin 到白天 3 的白天 1 上的 35 mg/m2 或 nedaplatin 由有是的 21 天的静脉内的注入的白天 1 上的 80 mg/m2 一个周期。石柜 1.0 标准被用来评估临床的效率，并且 WHO 毒性标准被用来评估有毒的反应，和 QOL 被用来评估生活的质量。所有病人被给 162 个周期的结果(至少 2 个周期，至多， 6 骑车) 并且所有病人的反应率被评估。有 2 完全的宽恕(CR ) ， 7 部分宽恕(PR ) ， 22 稳定的疾病(SD ) 和在这个组，的 19 进步疾病(PD ) 全面反应率是(RR ) 是 18.0% 并且疾病控制率(DCR )62.0% 。生活改进率的质量到达 58.0% 。主要有毒的反应包括了嗜中性白血球减少症， thrombocytopenia， hypemia，恶心，并且呕吐。大多数这些效果的严厉等级 III 和井被容忍。有在先进非小的房间肺癌症的治疗与铂相结合的 pemetrexed 或 pemetrexed 的结论化疗有效、安全、井可容忍，它能改进病人的生活的质量。

Molecularly targeted therapies for advanced or metastatic non-small-cell lung carcinoma

Non-small-cell lung cancer(NSCLC)remains the leading cause of cancer-related death in both men and women in the United States.Platinum-based doublet chemotherapy has been a standard for patients with advanced stage disease.Improvements in overall survival and quality of life have been modest.Improved knowledge of the aberrant molecular signaling pathways found in NSCLC has led to the development of biomarkers with associated targeted therapeutics,thus changing the treatment paradigm for many NSCLC patients.In this review,we present a summary of many of the currently investigated biologic targets in NSCLC,discuss their current clinical trial status,and also discuss the potential for development of other targeted agents.

Achievable complete remission of advanced non-small-cell lung cancer: Case report and review of the literature

Surgery is the first choice of treatment for patients with non-small-cell lung cancer(NSCLC), but few patients can be treated surgically because of either advanced disease or poor pulmonary function. Other therapies include radiotherapy and chemotherapy, as well as complementary and alternative therapies, usually with disappointing results. Bronchial artery infusion(BAI) is a manageable and effective method for treating advanced NSCLC. Outcome is good by BAI due to its repeatability and low toxicity. Icotinib hydrochloride is a newly developed and highly specific epidermal growth factor receptor(EGFR) tyrosine kinase inhibitor and has been safely and efficiently used to treat advanced NSCLC. We herein report a 73-year-old patient with chronic cough, who was diagnosed with advanced NSCLC with the EGFR mutation of L858 R substitution in exon 21, and treated with the combination of oral icotinib and BAI chemotherapy as the first-line therapy, which resulted in a satisfactory clinical outcome. Complete remission of advanced NSCLC can be achieved using the combination of oral icotinib and BAI chemotherapy.

Pharmacokinetics of gemcitabine in Chinese patients with non-small-cell lung cancer

To determine the pharmacokinetics of gemcitabine (2′,2′-difluorodeoxycytidine) in Chinese non-small-cell lung cancer (NSCLC) patients. Six study subjects were administered gemcitabine at a fixed dose rate of 10 mg/m2 per min (1200 mg/m2, two hours infusion) and carboplatin, and plasma gemcitabine concentrations were measured by ion-pair reversed-phase high-performance liquid chromatography (HPLC). 3P97 Pharmaceutical Kinetics Software was used for the calculation of pharmacokinetic parameters. The obtained mean parameters, elimnation half life (t1/2) (10.67±3.38 min), area under the curve (AUC) (7.55±1.53 (μg·h)/ml), and clearance (CL) (3940.05±672.08 ml/min), were consistent with those reported in literature. The hematologic toxicology result showed that the regimen was effective on and tolerated by the patients.

A phase I study of nimotuzumab plus docetaxel in chemotherapy- refractory/resistant patients with advanced non-small-cell lung cancer

Background： To determine the safety and therapeutic efficacy of nimotuzumab （h-R3） combined with docetaxel in advanced non-small-cell lung cancer （NSCLC） patients who have failed to respond to prior first-line chemotherapy. Methods： In this single-center, open-label, dose-escalating phase I trial, patients with epidermal growth factor receptor （EGFR）-expressing stage IV NSCLC were treated with nimotuzumab plus doeetaxel according to a dose escalation schedule. The safety and efficacy of the combination treatment were observed and analyzed.Results： There were 12 patients with EGFR-expressing stage IV NSCLC enrolled. The dose of nimotuzumab was escalated from 200 to 600 mg/week. The longest administration of study drug was 40 weeks at the 600 mg/week dose level. Grade Ⅲ-Ⅳ toxicities included neutropenia and fatigue, and other toxicities included rash. Dose-limiting toxicity occurred with Grade 3 fatigue at the 200 mg dose level of nimotuzumab and Grade 4 neutropenia with pneumonia at the 600 mg dose level of nimotuzumab. No objective responses were observed, and stable disease was observed in eight patients （66.7%）. The median progression-free survival （PFS） was 4.4 months in all patients, 1.3 months in patients with the EGFR mutation, and 4.4 months in those with wild type EGFR （EGFR WT）. The median survival time （MST） was 21.1 months in all patients, 21.1 months in patients with EGFR mutation, and 26.4 months in patients with EGFR WT. Conclusions： Nimotuzumab and docetaxel combination therapy was found to be well tolerated and efficacious. Further study of nimotuzumab is warranted in advanced NSCLC patients.

Impact of crizotinib on long-term survival of ALK-positive advanced non-small-cell lung cancer: A Chinese multicenter cohort study

Objective: Crizotinib has demonstrated promising efficacy in patients with anaplastic lymphoma kinase(ALK)-positive non-small-cell lung cancer(NSCLC) in clinical trials. We conducted this retrospective multicenter study to assess the outcomes of crizotinib therapy in, to our knowledge, a large sample cohort of patients with ALKpositive advanced NSCLC.Methods: We reviewed the medical records of 484 unselected ALK-positive NSCLC patients treated with crizotinib at 5 cancer centers in China from January 2013 to November 2017. Clinical data were collected from the initiation of crizotinib therapy to Response Evaluation Criteria in Solid Tumors(RECIST)-defined progressive disease(PD).Results: A total of 428 eligible ALK-positive NSCLC patients were enrolled, 273(63.8%) of whom received crizotinib as first-line treatment. The median progression-free survival(PFS) and overall survival(OS) from the initiation of crizotinib treatment were 14.4 [95% confidence interval(95% CI), 12.4-16.4] months and 53.4(95%CI, 33.7-73.1) months, respectively. In subgroup analyses, patients who received crizotinib as first-line treatment showed a higher disease control rate(DCR) and a longer median OS compared with second-/later-line crizotinib treatment(94.8% and OS not reached vs. 89.0% and 40.5 months, respectively). For 261 patients with RECISTdefined PD, multivariate Cox analysis revealed that in patients who received first-line crizotinib therapy, continued crizotinib beyond progressive disease(CBPD) and next-generation ALK inhibitors after crizotinib failure were associated with improved survival.Conclusions: This study has demonstrated the clinically meaningful benefit of crizotinib treatment in a large cohort of Chinese ALK-positive NSCLC patients. CBPD and next-generation ALK inhibitor treatment may provide improved survival after RECIST-defined progression on crizotinib.

Low Correspondence of EGFR Mutations in Tumor Tissue And Paired Serum of Non-Small-Cell Lung Cancer Patients

Objective： Epidermal growth factor receptor （EGFR） mutations are strong determinants of tumor response to EGFR tyrosine kinase inhibitors in non-small-cell lung cancer （NSCLC） patients. The aim of this study was to evaluate the correspondence between EGFR mutations in non-small-cell lung cancer tissues and in circulating DNA. Methods： The research was conducted in 50 non-small-cell lung cancer patients who had undergone curative surgery, and in whom both serum and neoplastic tissues were available. Meanwhile sera of 33 cases of advanced NSCLC patients were also analyzed. DNA were extracted from each sample. Mutations of EGFR in exonl8-21 were examined by PCR amplification method and direct sequencing. Results： EGFR mutations were detected in 15 （30%） of 50 neoplastic tissue samples, 6 cases were in-frame deletion del E746-A750 in exonl9, 9 cases were substitution in exon 21 （all were L858R except one was L861Q）, but no mutated DNA resulted in paired serum circulating DNA samples of 50 resectable patients. As the 33 advanced NSCLC patients, EGFR mutations were detected in only 2 serum circulating DNA samples, all were L858R mutation in exon 21. Conclusion： These data indicated that it was difficult to identify EGFR mutations in circulating DNA of NSCLC patients. The use of EGFR mutation in serum as a clinical method for decision making of TKI therapy is unsatisfactory.

Efficacy and safety of albumin-bound paclitaxel in treating recurrent advanced non-small-cell lung cancer

Objective： To observe the efficacy and safety of albumin-bound paclitaxel （ABP） monotherapy in treating recurrent advanced non-small-cell lung cancer （NSCLC）. Methods： We retrospectively analyzed the short-term efficacy and toxicities of ABP monotherapy in treating 21 patients who had previously undergone multiple cycles of therapy for their advanced NSCLC in our hospital since 2010. The treatment-related survival was also analyzed. Results： Of these 21 patients, the best overall response was partial response （PR） in 6 patients （28.6%）, stable disease （SD） in I0 patients （47.6%）, and progressive disease （PD） in 5 patients （23.8%）. The overall response rate （ORR） was 28.6% and the disease control rate （DCR） （PR ＋ SD） was 76.2%. The median progression-flee survival （PFS） was 4.0 months （95% CI, 5.0-7.0 months）. The main grade 3/4 toxicities included neutropenia （11.1%）, peripheral nerve toxicity （5.6%）, muscle and joint aches （5.6%）, and fatigue （5.6%）. Conclusions： The ABP monotherapy can achieve good objective response in advanced NSCLC patients who have previously received multiple cycles of treatment and be well tolerated.

Comparison of pharmacokinetics,efficacy and toxicity profile of gemcitabine using two different administration regimens in Chinese patients with non-small-cell lung cancer

Objective:To conduct a randomized comparative trial of pharmacokinetics, efficacy and toxicity profile treatment with 1 200 mg/m2 gemcitabine using standard 30-min infusion or fixed dose rate (FDR) infusion 10 mg/(m2·min) on days 1 and 8 plus carboplatin AUC (area under curve) 5 on day 1 in Chinese non-small-cell cancer patients. Twelve patients were enrolled in this study. Methods:Plasma gemcitabine concentrations were measured by ion-pair reversed phase high performance liquid chromatography. Antitumoral activity and toxicity of gemcitabine was assessed according to World Health Organization criteria. Results:The obtained mean parameters, such as T1/2 (elimination half time), AUC, and CL (clearance), were consistent with those reported in literature. Qualified response rate in our study was 33.3% for standard arm and 50% for FDR arm. Additional 50% and 33.3% patients contracted stable disease (SD) in standard arm and FDR arm, respectively. The predominant toxicity was hematologic, and patients in the standard infusion arm experienced consistently more hematologic toxicity. Conclusion:Pharmacokinetic and clinical data in this trial support the continued evaluation of the FDR infusion strategy with gemcitabine.

Immediate Versus Delayed Treatment with EGFR Tyrosine Kinase Inhibitors after First-line Therapy in Advanced Non-small-cell Lung Cancer

Objective： To analyze the outcomes of patients who received TKI immediately after the first-line without progression as maintenance treatment （immediate group） vs. those received delayed treatment upon disease progression as second-line therapy （delayed group）. Methods： The study included 159 no-small-cell lung cancer （NSCLC） patients who received gefitinib or erlotinib as maintenance treatment in the immediate group （85 patients） or as second-line therapy in the delayed group （74 patients）. The primary end point was progression-free survival （PFS）. EGFR mutation status was detected using denaturing high-performance liquid chromatography （DHPLC）. Results： PFS was 17.3 and 16.4 months in the immediate and delayed groups, respectively （hazard ratio [HR], 0.99; 95% Confidence Interval [CI]： 0.69-1.42; P=0.947）. In a subgroup analysis that included only patients with EGFR mutation, however, PFS was significantly longer in the immediate group than in the delayed group （HR, 0.48; 95% CI： 0.27-0.85; P=0.012）. In patients with wild type EGFR, the risk for disease progression was comparable between the two groups （HR, 1.23; 95% CI： 0.61-2.51; P=0.564）. No significant difference was demonstrated between the immediate and delayed group in terms of the overall survival （OS） （26.1 months vs. 21.6 months, respectively; HR=0.53; 95% CI： 0.27 to 1.06; P=0.072）. There was also no difference in the incidence of adverse events between the two groups. Conclusions： EGFR TKI maintenance improves PFS in patients with EGFR mutation. Prospectively designed clinical studies that compare TKI immediate vs. delayed treatment after first-line chemotherapy upon disease progression are needed.

Involvement of miR-214 and miR-375 in Malignant Features of Non-Small-Cell Lung Cancer by Down-Regulating CADM1

A tumor suppressor gene, CADM1, encoding an immunoglobulin superfamily cell adhesion molecule, is inactivated in various cancers, including non-small-cell lung cancer (NSCLC). Although promoter methylation is one of the mechanisms to suppress CADM1 expression, about half of tumors lacking CADM1 expression do not show methylation of the gene promoter. We herein investigated the possible involvement of microRNA (miRNA) in the down-regulation of CADM1. Using computational algorithms, miR-214 and miR-375 were identified as candidate miRNAs targeting CADM1. A luciferase reporter assay demonstrated that miR-214 and miR-375 repressed the promoter activity through 3’-UTR of CADM1. Quantitative RT-PCR analysis demonstrated that miR-214 and miR-375 was highly expressed in 21 (62%) and 17 cases (50%) of 34 primary NSCLCs. Notably, increased expression of miR-214 was preferentially observed in tumors with advanced pathological stages and in those lacking CADM1 expression but were not associated with the promoter methylation, suggesting that miR-214-mediated silencing would be another mechanism to suppress CADM1 expression. On the other hand, introduction of miR-214 or miR-375 into NSCLC cells decreased CADM1 protein expression. Furthermore, overexpression of miR-214 enhanced anchorage-independent growth of NSCLC cells, A549, whereas transfection of miRNA inhibitor, miR-214 or miR-375, significantly suppressed the in vitro wound healing activity of HCC827 cells. These findings suggest that overexpression of miR-214 and miR-375 could participate in the malignant features of NSCLC through down-regulating CADM1 and would provide a potential target for the treatment of a subset of NSCLC.

EXPRESSION OF P120ctn IN NON-SMALL-CELL LUNG CANCER: A CLINICOPATHOLOGICAL STUDY

Objective: To investigate the expression of p120ctn in non-small-cell lung cancer (NSCLC) and its relationship with clinicopathological factors and prognosis. Methods: p120ctn expression was tested by immunohistochemistry for 80 tumors from patients with non-small-cell lung cancer. Correlations were investigated between p120ctn immunostaining in primary tumors and clinicopathological characteristics and survival. Results: Abnormal expression of p120ctn was found in 68/80(85%) tumors in which 43 cases had cytoplasmic staining. Abnormal staining of p120ctn was related with high TNM stage (P=0.003) and nodal metastasis (P=0.024). However, there was no correlation between altered expression with poor differentiation and histological type. According to Kaplan-Meier survival estimate, the expression of p120ctn was related to the poor survival (P=0.015) of patients. A Cox regression analysis revealed that p120ctn expression was a significant independent factor in the prediction of survival for patients with non-small-cell lung cancer (P=0.008). Conclusion: altered expression of p120ctn was found in non-small-cell lung cancers and was correlated with lymph node metastasis and prognosis. From a practical point of view, the expression of p120ctn can be of prognostic value for patients with non-small-cell lung cancer.