Shi Y.,Peking Union Medical College |
Shi Y.,Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs |
Zhang L.,Sun Yat Sen University |
Zhang L.,Peking Union Medical Hospital |
And 30 more authors.
The Lancet Oncology | Year: 2013
Background: Icotinib, an oral EGFR tyrosine kinase inhibitor, had shown antitumour activity and favourable toxicity in early-phase clinical trials. We aimed to investigate whether icotinib is non-inferior to gefitinib in patients with non-small-cell lung cancer. Methods: In this randomised, double-blind, phase 3 non-inferiority trial we enrolled patients with advanced non-small-cell lung cancer from 27 sites in China. Eligible patients were those aged 18-75 years who had not responded to one or more platinum-based chemotherapy regimen. Patients were randomly assigned (1:1), using minimisation methods, to receive icotinib (125 mg, three times per day) or gefitinib (250 mg, once per day) until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival, analysed in the full analysis set. We analysed EGFR status if tissue samples were available. All investigators, clinicians, and participants were masked to patient distribution. The non-inferiority margin was 1·14; non-inferiority would be established if the upper limit of the 95% CI for the hazard ratio (HR) of gefitinib versus icotinib was less than this margin. This study is registered with ClinicalTrials.gov, number NCT01040780, and the Chinese Clinical Trial Registry, number ChiCTR-TRC-09000506. Findings: 400 eligible patients were enrolled between Feb 26, 2009, and Nov 13, 2009; one patient was enrolled by mistake and removed from the study, 200 were assigned to icotinib and 199 to gefitinib. 395 patients were included in the full analysis set (icotinib, n=199; gefitinib, n=196). Icotinib was non-inferior to gefitinib in terms of progression-free survival (HR 0·84, 95% CI 0·67-1·05; median progression-free survival 4·6 months [95% CI 3·5-6·3] vs 3·4 months [2·3-3·8]; p=0·13). The most common adverse events were rash (81 [41%] of 200 patients in the icotinib group vs 98 [49%] of 199 patients in the gefitinib group) and diarrhoea (43 [22%] vs 58 [29%]). Patients given icotinib had less drug-related adverse events than did those given gefitinib (121 [61%] vs 140 [70%]; p=0·046), especially drug-related diarrhoea (37 [19%] vs 55 [28%]; p=0·033). Interpretation: Icotinib could be a new treatment option for pretreated patients with advanced non-small-cell lung cancer. Funding: Zhejiang Beta Pharma (China), the Chinese National Key Special Program for Innovative Drugs, the 863 Project, and Zhejiang Provincial Key Special Program. © 2013 Elsevier Ltd.
PubMed | Fudan University, Wannan Medical College, Jilin Province Cancer Hospital and Shanghai JiaoTong University
Type: Journal Article | Journal: Journal of thoracic disease | Year: 2016
To analyze the clinicopathological features and prognosis of younger patients with esophageal adenocarcinoma (EAC).A total of 2,601 patients diagnosed with EAC between 1988 and 2011 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. All patients underwent primary tumor resection and regional lymphadenectomy without preoperative radiotherapy. The patients were into four age groups (<45, 45-59, 60-74, 75), with 94, 813, 1,272 and 422 patients in each group respectively.Patients in the age <45 group were more likely to have lymph node (LN) metastasis (P=0.002), postoperative radiotherapy (P<0.001) and advanced T and N stage (P=0.003, 0.014) compared to the other three groups. We then conducted two Cox proportional hazards model adjusted for the sex, race, number of LNs examined, histological grade, postoperative radiation. The hazard ratio (HR) was higher in patients <45 y and the survival rate were paradoxically lower compared to the patients between 45-60 years old (P=0.046, 0.039).The patients <45 y had the most aggressive clinicopathological features of EAC and poorer survival rate after radical esophagectomy.
Liu X.,Jilin University |
Pei C.,Jilin Province Peoples Hospital |
Yan S.,Jilin Province Cancer Hospital |
Liu G.,Jilin University |
And 4 more authors.
Tumor Biology | Year: 2015
Recent evidence demonstrated an enhanced metastasis of non-small cell lung cancer (NSCLC) cells induced by lipopolysaccharide (LPS) stimulation, which reflected an important role of inflammation in tumor progression. However, the underlying mechanisms still remain unclear. Here, we evaluated the potential role of reactive oxygen species (ROS) in Toll-like receptor 4 (TLR4) signaling enhanced NSCLC metastasis. NSCLC cells were isolated from clinical surgical tissues. We found that LPS stimulation of NSCLC cells facilitates their metastasis that was accompanied by increased ROS production and could be abrogated by ROS inhibition. NADPH oxidase was essential for TLR4 signaling-enhanced NSCLC metastasis. Elevated NADPH oxidase 1 (NOX1) expression by LPS stimulation was observed. Blockade of NOX1 with ML171 alleviated enhanced NSCLC metastasis by TLR4 signaling. Enforced NOX1 expression promoted TLR4 signaling-enhanced NSCLC metastasis, while decreased NOX1 expression inhibited TLR4 signaling-enhanced NSCLC metastasis. Further, NOX1 could regulate the expression of CXCR4 and matrix metallopeptidase 9 (MMP9) in NSCLC cells. NOX1 expression in tumor tissues was correlated with TLR4 expression and clinical stages in NSCLC patients. Finally, inhibition of NOX1/ROS prevented enhanced lung tumor burdens of NSCLC by LPS-induced acute lung infection. Our findings demonstrated a crucial role of NOX1-dependent ROS for TLR4 signaling to enhance the metastasis of NSCLC, which could further the understanding of NSCLC pathogenesis and helpful for developing novel therapeutics for NSCLC. © 2015, International Society of Oncology and BioMarkers (ISOBM).
Zhang S.,Jilin University |
Zhang S.,Jilin Province Cancer Hospital |
Liu X.,Jilin Province Cancer Hospital |
Zhang Y.,Jilin University |
And 2 more authors.
International Journal of Clinical and Experimental Pathology | Year: 2013
Histone acetyltransferases (HATs) regulate many critical cancer events, including transcriptional regulation of oncogene and tumor suppressors, chromatin structure and DNA damage response. Abnormal expression of HATs has been reported in a number of cancers. However, cellular functions of HATs in cancer and molecular mechanisms remain largely unclear. Here, we performed a lentiviral vector-mediated RNAi screen to systematically address the function of HATs in lung cancer cell growth and viability. We identified 8 HATs genes involved in A549 cell viability. Further experiments showed that KAT8 regulates G2/M cell cycle arrest through AKT/ERK-cyclin D1 signaling. Moreover, KAT8 inhibition led to p53 induction and subsequently reduced bcl- expression. Our results demonstrate an important role of KAT8 in cancer and suggest that KAT8 could be a novel cancer therapeutic target.
PubMed | Jilin University and Jilin Province Cancer Hospital
Type: Journal Article | Journal: International journal of molecular medicine | Year: 2016
The expression levels of the copper transporter P-type adenosine triphosphatase(ATP7B) are known correlate with tumor cell sensitivity to cisplatin. However, the mechanisms underlying cisplatin resistance remained poorly understood. Therefore, in the present study, we treated Hep-2cells and in-house-developed vincristine-resistant Hep-2vcells with 50, 100, or 200M cisplatin and assessed cell viability after 24 or 48h. Hep-2v cells were shown to be resistant to 50-200M cisplatin. Furthermore, using immunofluorescence staining and western blot analysis, we noted that ATP7B, but not copper-transporting ATPase1(ATP7A), expression was significantly increased in Hep-2v cells, and this increase was maintained at a higher level compared with Hep-2cells. As ATP7B is a target of microRNA 133a(miR133a), the ability of miR133a to influence cisplatin sensitivity in Hep-2v cells was then assessed by CCK-8 assay. We noted that miR133a expression was lower in both Hep-2 and Hep-2vcells compared with epithelial NP69 cells. Following treatment with 50M cisplatin, in Hep-2v cells expressing exogenous miR133a we noted reduced ATP7B expression, and these cells had a significantly lower survival rate compared with the control. The present study demonstrates that miR133a enhances the sensitivity of multidrug-resistant Hep-2v cells to cisplatin by downregulating ATP7B expression.
PubMed | Fudan University, Jilin University and Jilin Province Cancer Hospital
Type: | Journal: Forensic science international. Genetics | Year: 2016
In this study, 17 Y chromosomal short tandem repeats (Y-STRs) were analyzed in 302 male individuals from the Chinese Han and Korean populations of Jilin Province. The haplotype diversities of two populations reached 0.99969 and 0.99874, respectively. The Jilin Han and Korean populations differed from each other significantly. The Jilin Han population showed no significant difference from almost any other Han population, but it did show significant differences from most other Chinese ethnic populations. The haplotype frequencies in the Jilin Korean population studied here showed significant differences from all reference populations in earlier reports. These data provide a reference for the Y-STR database in Jilin Province, and they may be valuable for population genetic analysis.
Cha N.,Shenyang University |
Lv M.,Jilin Province Cancer Hospital |
Zhao Y.-J.,Shenyang Medical College |
Yang D.,Shenyang University |
And 2 more authors.
Respirology | Year: 2014
Background and objective Bronchial brushing is important for cytological diagnosis of lung carcinoma; however, cytological evaluation alone remains relatively insensitive. The aim of this study was to assess the diagnostic utility of vascular endothelial growth factor (VEGF) messenger ribonucleic acid (mRNA) and specificity protein 1 (SP1) mRNA in bronchial brushings in patients with or without lung cancer. Methods VEGF mRNA and SP1 mRNA were measured in liquid-based cells from bronchial brushings in patients with verified lung cancer (n = 93) and with benign lung disease that included tuberculosis (n = 51). This was done using the reverse-transcription polymerase chain reaction. Results Both VEGF mRNA and SP1 mRNA were significantly more likely to be expressed in the cancer group than in the control (benign) group, whatever their cell type. It was also more often found in the tuberculosis group than in the inflammation group (P < 0.01). In the cancer group, VEGF mRNA was significantly correlated with SP1 mRNA (P < 0.01). Of the 36 false negative cytology results, 30 gave positive results for VEGF mRNA and 34 for SP1 mRNA. The four false positive VEGF results were all diagnosed as tuberculosis. VEGF mRNA gave the highest diagnostic performance with serial use: sensitivity 89.2% and accuracy 90.3%. This was significantly better than cytology (P < 0.01). Conclusions Detection of VEGF mRNA and SP1 mRNA in bronchial brushing cells may be used as an ancillary tool to cytological diagnosis for detection of early-stage lung cancer. It may also help distinguish tuberculosis from other causes of lung inflammation. © 2014 Asian Pacific Society of Respirology.
A randomized phase II clinical trial of nab-paclitaxel and carboplatin compared with gemcitabine and carboplatin as first-line therapy in locally advanced or metastatic squamous cell carcinoma of lung
Yang J.-J.,Shandong Academy of Sciences |
Huang C.,Fujian Province Cancer Hospital |
Chen G.-Y.,Heilongjiang Province Cancer Hospital |
Song Y.,Nanjing General Hospital |
And 4 more authors.
BMC Cancer | Year: 2014
Background: Recent advances have shown that histology and genetic biomarkers are important in patient selection, which have led to significantly better outcomes for lung cancer patients. However, most new treatments only apply to adenocarcinoma or non-squamous, and in squamous carcinoma there is little breakthrough. In a phase III trial nab-paclitaxel plus carboplatin showed superior response rate over paclitaxel and carboplatin. In subgroup analysis the squamous histology appeared to be a predictive factor to nab-paclitaxel treatment.Methods/Design: This is an open-label, randomized, active controlled phase II trial. A total of 120 untreated advanced squamous lung cancer patients are randomized at a 1:1 ratio to receive nab-paclitaxel (135 mg/m2, d1, 8, q3w) plus carboplatin (AUC 5, d1, q3w) or gemcitabine (1,250 mg/m2, d1, 8, q3w) and carboplatin (AUC 5, d1, q3w). The primary endpoint is objective response rate and the second endpoints are progression free survival, overall survival, safety and biomarkers associated with nab-paclitaxel. The treatment will continue up to six cycles or intolerable toxicity.Discussion: This ongoing trial will be the first prospective randomized trial to explore the efficacy of nab-paclitaxel as the first-line treatment specifically in squamous carcinoma of lung.Study number: CTONG1002. Trial Registration: Clinicaltrials.gov reference: NCT01236716. © 2014 Yang et al.; licensee BioMed Central Ltd.
PubMed | Jilin province Cancer Hospital and Soochow University of China
Type: | Journal: Oncotarget | Year: 2016
Rottlerin, isolated from a medicinal plant Mallotus phillippinensis, has been demonstrated to inhibit cellular growth and induce cytoxicity in glioblastoma cell lines through inhibition of calmodulin-dependent protein kinase III. Emerging evidence suggests that rottlerin exerts its antitumor activity as a protein kinase C inhibitor. Although further studies revealed that rottlerin regulated multiple signaling pathways to suppress tumor cell growth, the exact molecular insight on rottlerin-mediated tumor inhibition is not fully elucidated. In the current study, we determine the function of rottlerin on glioma cell growth, apoptosis, cell cycle, migration and invasion. We found that rottlerin inhibited cell growth, migration, invasion, but induced apoptosis and cell cycle arrest. Mechanistically, the expression of Cdc20 oncoprotein was measured by the RT-PCR and Western blot analysis in glioma cells treated with rottlerin. We observed that rottlerin significantly inhibited the expression of Cdc20 in glioma cells, implying that Cdc20 could be a novel target of rottlerin. In line with this, over-expression of Cdc20 decreased rottlerin-induced cell growth inhibition and apoptosis, whereas down-regulation of Cdc20 by its shRNA promotes rottlerin-induced anti-tumor activity. Our findings indicted that rottlerin could exert its tumor suppressive function by inhibiting Cdc20 pathway which is constitutively active in glioma cells. Therefore, down-regulation of Cdc20 by rottlerin could be a promising therapeutic strategy for the treatment of glioma.