Jun Pei

Comparison of PG-SGA, SGA and body-composition measurement in detecting malnutrition among newly diagnosed lung cancer patients in stage IIIB/IV and benign conditions.

Assessment tools and body-composition measurements are useful in diagnosing malnutrition. Which one is better for lung disease patients is unclear. The objectives of the present study are: to assess relationships between different methods of nutritional measurements in lung diseases patients; to determine which one is better in diagnosing malnutrition for lung disease patients; and to determine whether lung cancer patients can be differentiated from benign lung disease patients using different measurements. A total of 96 newly diagnosed primary lung cancer patients in stage IIIB/IV and 52 benign lung disease patients nutritional status were assessed according to the SGA, the scored PG-SGA, and serum albumin, prealbumin, transferrin, hemoglobin, total lymphocyte count, body mass index (BMI), and weight. A total of 40% of lung cancer patients were severely malnourished, with men or elder having a higher rate of malnutrition. Significantly lower values of weight, BMI, total lymphocyte count, transferrin, prealbumin and serum albumin were found for them. Age, sex, weight, weight half year ago and prealbumin are in the regression equation to predict them. For benign lung disease patients, 21.2% were severely malnourished with significantly lower values of weight and transferrin. Age and prealbumin are in the equation to predict severely malnourished benign lung disease patients. The highest receiver operation characteristic area under the curve was found for the PG-SGA score, BMI and weight. PG-SGA global rating, age and iron-transferring protein are in the equation for predicting disease status. The SGA and PG-SGA are appropriate for identifying malnutrition in lung disease patients. Lung cancer patients can be differentiated from benign conditions by PG-SGA.

XPA gene rs1800975 single nucleotide polymorphism and lung cancer risk: a meta-analysis

No clear consensus has been reached on the XPA gene rs1800975 polymorphism and lung cancer risk. We performed a meta-analysis in an effort to systematically explore the possible association. We conducted a computer retrieval of PubMed, Embase, Wanfang, China National Knowledge Infrastructure Platform, and VIP databases prior to November 2013. References of retrieved articles were also screened. The fixed- and the random-effects model were applied for dichotomous outcomes to combine the results of the individual studies. According to the inclusion criteria, 10 articles (11 studies) were finally included. In overall, statistical association could be found between rs1800975 polymorphism and lung cancer in recessive genetic model [AA vs. (AG + GG): P = 0.02, OR = 1.16, 95% CI 1.02–1.31, Pheterogeneity = 0.14, fixed-effects model]. In the East Asians, significant association was found in allele comparison model (A vs. G: P = 0.03, OR = 1.13, 95% CI 1.01–1.26, Pheterogeneity = 0.39, fixed-effects model), in recessive genetic model [AA vs. (AG + GG): P = 0.005, OR = 1.30, 95% CI 1.08–1.56, Pheterogeneity = 0.58, fixed-effects model] and in the homozygote comparison (AA vs. GG: P = 0.02, OR = 1.30, 95% CI 1.04–1.63, Pheterogeneity = 0.39, fixed-effects model). No evidence suggested that rs1800975 polymorphism might associate with lung cancer in other ethnicities. Stratification analysis performed by histologic types indicated that AA genotype might represent a risk factor for squamous cell carcinoma [AA vs. (AG + GG): P = 0.01, OR = 1.42, 95% CI 1.08–1.86, Pheterogeneity = 0.27, fixed-effects model; AA vs. GG: P = 0.03, OR = 1.43, 95% CI 1.04–1.96, Pheterogeneity = 0.21, fixed-effects model]. No association was observed in adenocarcinoma subgroup. Our study suggested that XPA rs1800975 polymorphism might associate with lung cancer risk in overall and in East Asians. This polymorphism might also associate with squamous cell carcinoma.

Efficacy and safety evaluation of icotinib in patients with advanced non-small cell lung cancer.

OBJECTIVE To evaluate the efficacy and safety of icotinib hydrochloride in patients with advanced non-small cell lung cancer (NSCLC). METHODS A total of 89 patients with stage IIIB or IV NSCLC received icotinib at a dose of 125 mg administered 3 times a day. Icotinib treatment was continued until disease progression or development of unacceptable toxicity. RESULTS A total of 89 patients were assessable. In patients treated with icotinib, the overall response rate (RR) was 36.0% (32/89), and the disease control rate (DCR) was 69.7% (62/89). RR and DCR were significantly improved in patients with adenocarcinoma versus non-adenocarcinoma (P<0.05). The symptom improvement rate was 57.3% (51/89), and the main symptoms improved were cough, pain, chest distress, dyspnea, and Eastern Cooperative Oncology Group performance status. The main toxic effects were rash [30/89 (33.7%)] and diarrhea [15/89 (16.9%)]. The level of toxicity was typically low. CONCLUSIONS The use of icotinib hydrochloride in the treatment of advanced NSCLC is efficacious and safe, and its toxic effects are tolerable.

Combination of chemotherapy and gefitinib as first-line treatment for patients with advanced lung adenocarcinoma and sensitive EGFR mutations: A randomized controlled trial

To explore the optimal treatment strategy for patients who harbor sensitive EGFR mutations, a head‐to‐head study was performed to compare chemotherapy and gefitinib in combination or with either agent alone as first‐line therapy, in terms of efficacy and safety. A total of 121 untreated patients with advanced lung adenocarcinoma who harbored sensitive EGFR mutations were randomly assigned to receive gefitinib combined with pemetrexed and carboplatin, pemetrexed plus carboplatin or gefitinib alone. The progression‐free survival (PFS) of patients in the combination group (17.5 months, 95% CI, 15.3–19.7) was longer than that of patients in the chemotherapy group (5.7 months, 95% CI, 5.2–6.3) or gefitinib (11.9 months, 95% CI, 9.1–14.6) group. The (hazard ratios) HRs of PFS for the combination group vs. chemotherapy and gefitinib groups were 0.16 (95% CI, 0.09–0.29, p < 0.001) and 0.48 (95% CI, 0.29–0.78, p = 0.003), respectively. The overall response rate (ORR) in the combination therapy group, chemotherapy group and the gefitinib group was 82.5%, 32.5% and 65.9%, respectively. The combinational strategy resulted in longer overall survival (OS) than chemotherapy (HR = 0.46, p = 0.016) or gefitinib (HR = 0.36, p = 0.001) alone. Our finding suggested that treatment with pemetrexed plus carboplatin combined with gefitinib could provide better survival benefits for patients with lung adenocarcinoma harboring sensitive EGFR mutations.

Downregulation of HIF-1α inhibits the proliferation and invasion of non-small cell lung cancer NCI-H157 cells

Lung cancer, specifically non-small cell lung cancer (NSCLC), is the leading cause of cancer-associated mortality in the world. In previous years, almost no significant advancements have been made towards the molecular characterization of NSCLC, which highlights the requirement for novel target genes. Hypoxia inducible factor-1α (HIF-1α) is known to be essential in tumorigenesis, as it regulates the expression of numerous factors that are involved in angiogenesis, cellular proliferation and apoptosis. However, no direct association between HIF-1α and NSCLC treatment has previously been established. The aim of the present study was to characterize the effect of HIF-1α on NSCLC and to explore the possible mechanism. Additionally, HIF-1α small interfering (si)RNA and diamminedichloroplatinum (DDP) were used in combination to explore the combined effects on NSCLC cells. Lung carcinoma NCI-H157 cells were treated with HIF-1α small interfering (si)RNA, 5 µg/ml DDP or a combination of the two, and the proliferation, apoptosis and invasion ability of the cells were detected using a cell counting kit-8 assay, Annexin V/propidium iodide staining and a Transwell assay, respectively. In addition, the protein levels of caspase-3/9, anti-apoptotic protein B-cell lymphoma-2 (Bcl-2), vascular endothelial growth factor (VEGF), pigment epithelium-derived factor (PEDF), phosphoinositide 3-kinase (PI3K), phosphorylated (p-)PI3K, protein kinase B (AKT), p-AKT, extracellular signal-regulated kinase (ERK) and p-ERK were detected using western blot analysis. Similar to DPP treatment, HIF-1α siRNA treatment may reduce cell proliferation and the invasiveness of tumor cells while promoting apoptosis. Additionally, HIF-1α siRNA may increase the levels of the apoptotic proteins caspases 3 and 9 and inhibit the expression of Bcl-2. These anti-tumor effects may be acting through the VEGF/PEDF, PI3K/AKT and Raf/mitogen-activated protein kinase kinase/ERK signaling pathways. The effects of HIF-1α siRNA may be strengthened by DDP. The present data indicated that HIF-1α siRNA is important in the inhibition of NSCLC cells. Additionally, the effects of HIF-1α siRNA may be strengthened by DDP, which suggests that HIF-1α siRNA may be combined with DDP for the treatment of tumors.

Serum dickkopf-1 as a clinical and prognostic factor in non-small cell lung cancer patients with bone metastases

Background The study was designed to evaluate the association between serum dickkopf-1 (DKK1) and non-small cell lung cancer (NSCLC) bone metastases. Materials and Methods Serum DKK1 levels were quantified in 470 NSCLC patients, 140 with osseous metastases, 178 with extraosseous metastases, and 152 with early stage in complete remission. The Receiver Operating Characteristic (ROC) curve enabled us to identify a threshold value to distinguish patients with bone metastases. Results Serum DKK1 levels in patients with osseous metastases were significantly higher than in the other 2 groups (P < 0.001). ROC curves showed that the optimum cutoff was 311.8 pg/ml (area under curve 0.791, 95% confidence interval 0.739–0.843, sensitivity 77.1% and specificity 71.4%). Of interest, serum DKK1 correlated with the number of bone lesions (P = 0.042) and associated with the poor survival in NSCLC patients with osseous metastases (P = 0.029). Conclusions Our data shows that serum DKK1 can be used for the detection of NSCLC bone metastases. More importantly this is the first report to show that serum DKK1 is a good predictor of poor prognosis in NSCLC patients with bone metastases.BACKGROUND The study was designed to evaluate the association between serum Dickkopf-1(DKK1)and non-small cell lung cancer(NSCLC) bone metastases. MATERIALS AND METHODS Serum DKK1 levels were quantified in 470 NSCLC patients, 140 with osseous metastases, 178 with extraosseous metastases, and 152 with early stage in complete remission. The Receiver Operating Characteristic (ROC) curve enabled us to identify a threshold value to distinguish patients with bone metastases. RESULTS Serum DKK1 levels in patients with osseous metastases were significantly higher than in the other 2 groups (P < 0.001). ROC curves showed that the optimum cutoff was 311.8 pg/ml (area under curve 0.791, 95% confidence interval 0.739-0.843, sensitivity 77.1% and specificity 71.4%). Of interest, serum DKK1 correlated with the number of bone lesions (P = 0.042) and associated with the poor survival in NSCLC patients with osseous metastases (P = 0.029). CONCLUSIONS Our data shows that serum DKK1 can be used for the detection of NSCLC bone metastases. More importantly this is the first report to show that serum DKK1 is a good predictor of poor prognosis in NSCLC patients with bone metastases.

Multivariate survival analysis of patients with stage I NSCLC

BACKGROUND AND OBJECTIVE The effectiveness of adjuvant chemotherapy in providing survival advantage for stage I non-small cell lung cancer (NSCLC) patients, especially those with stage Ib NSCLC, remains to be determined. The seventh edition of the Tumor Node Metastasis (TNM) Classification of Malignant Tumors is due to be published in 2009. The aim of the current study is to validate the value of this classification in Chinese early-stage NSCLC. The benefits of adjuvant chemotherapy to patients with early-stage NSCLC were also assessed. METHODS The new staging project was validated in 433 patients who underwent complete surgical resection for early-stage NSCLC at the Single Institution of Shanghai Chest Hospital from June 1998 to June 2010. This new parameter was combined with other well-established prognostic factors, and multivariate survival analysis were performed. Variables in the analysis included age, gender, history of smoking, pathologic type, type of resection (pneumonectomy, lobectomy, bilobectomy, and sleeve resection), tumor size (largest tumor dimension), T-status, lymphovascular vessel invasion, and adjuvant chemotherapy. RESULTS The three-year overall survival rates for females and males are 89.22% and 77.53%, respectively (P=0.001,8). Elder patients have worse prognoses: the survival rates for those aged ≥70 and <70 are 70.64% and 85.85%, respectively (P=0.000,1). The three-year overall survival rates of patients whose tumors measured no larger than 2 cm in biggest diameter or larger than 2 cm but no larger than 3 cm are 95.15% and 85.71%, respectively. For those with tumors larger than 3 cm but smaller than 5 cm or larger than 5 cm but smaller than 7 cm, the survival rates are 74.80% and 60.47%, respectively (P<0.000,1). Multivariate analysis reveals that age, gender, vascular vessel invasion, pathologic type, and visceral pleural involvement are significant predictive factors of the overall survival. CONCLUSIONS The tumor size and pathologic type are significant independent prognostic factors in stage I NSCLC. The survival rates of patients with adenocarcinoma are higher than those of patients with other types of NSCLC. Female patients and those without a history of smoking have a better outcome. Results suggest that patients with the Ib stage of the disease can benefit from adjuvant chemotherapy.

Potential Antitumor Activity of SIM-89 in Non-Small Cell Lung Cancer Cells.

Purpose c-Met and its ligand, hepatocyte growth factor (HGF), play a critical role in oncogenesis and metastatic progression. The aim of this study was to identify inhibited enzymogram and to test the antitumor activity of SIM-89 (a c-Met receptor tyrosine kinase inhibitor) in non-small cell lung cancer. Materials and Methods Z′-LYTE kinase assay was employed to screen the kinase enzymogram, and mechanism of action (MOA) analysis was used to identify the inhibited kinases. Cell proliferation was then analyzed by CCK8 assay, and cell migration was determined by transwell assay. The gene expression and the phosphorylation of c-Met were examined by realtime-PCR and western blotting, respectively. Finally, the secretion of HGF was detected by ELISA assay. Results c-Met, activated protein kinase (AMPK), and tyrosine kinase A (TRKA) were inhibited by SIM-89 with the IC50 values of 297 nmol/L, 1.31 µmol/L, and 150.2 nmol/L, respectively. SIM-89 exerted adenosine triphosphate (ATP) competitive inhibition on c-Met. Moreover, the expressions of STAT1, JAK1, and c-Met in H460 cells were decreased by SIM-89 treatment, and c-Met phosphorylation was suppressed in A549, H441, H1299, and B16F10 cells by the treatment. In addition, SIM-89 treatment significantly decreased the level of HGF, which accounted for the activation of c-Met receptor tyrosine kinase. Finally, we showed cell proliferation inhibition and cell migration suppression in H460 and H1299 cells after SIM-89 treatment. Conclusion In conclusion, SIM-89 inhibits tumor cell proliferation, migration and HGF autocrine, suggesting its potential antitumor activity.

Lentivirus-mediated knockdown of CTDP1 inhibits lung cancer cell growth in vitro.

AbstractBackground CTDP1 catalyzes serine phosphorylation and dephosphorylation of the mobile carboxy-terminal domain of the RNA polymerase II. It is conserved among eukarya and is essential for cell growth for its ability in regulation of transcription machinery. However, its function in the process of tumorigenesis is unclear. In the present study, we aim to explore the roles of CTDP1 in the progression of human lung cancer. To our knowledge, this is the first study that reports the functions of CTDP1 in human lung cancer.Methods We first detected the expression level of CTDP1 in four human lung cancer cell lines: H-125, H1299, LTEP-A-2 and NCI-H446 by semiquantitative RT-PCR. We compared the expression level of CTDP1 in lung cancer tissues and paired adjacent normal tissues on 29 pathologically confirmed patients by real-time quantitative PCR. To further explore the effect of CTDP1 on cell proliferation, a lentiviral vector expressing CTDP1 short hairpin RNA (shRNA) was constructed and infected into human lung cell lines H1299. Interference efficiency was determined by western blot analysis and real-time quantitative PCR. The effects of knockdown of CTDP1 on cell growth, cell cycle and apoptosis and cell colony formation were explored by Cellomics, fluorescence-activated cells sorting and fluorescence microscopy, respectively.ResultsCTDP1 was expressed in all four human lung cancer cell lines. The expression of CTDP1 in tumor tissues was significantly higher than paired adjacent normal tissues in 29 patients with lung cancer. The expression of CTDP1 was markedly reduced in cells infected with lentivirus delivering shRNA against CTDP1. Inhibition of CTDP1 expression significantly suppressed cell growth, induced G0/G1 phase arrest and repressed cell colony formation.ConclusionsOur results demonstrated that CTDP1 was upregulated in human lung cancer tissues. In addition, it implied that CTDP1 played an important role in cell proliferation and may be a useful therapeutic target in human lung cancer.