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// Puyuan Xing 1, * , Shouzheng Wang 1, * , Xuezhi Hao 1 , Tongtong Zhang 1 , Junling Li 1 1 Department of Medical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China * These authors contributed equally to this work and should be considered co-first authors Correspondence to: Junling Li, email: lijunling@cicams.ac.cn Keywords: NSCLC, crizotinib, brain metastasis, chinese, real world Received: June 29, 2016 Accepted: October 28, 2016 Published: November 07, 2016 ABSTRACT Brain metastasis in non small cell lung cancer (NSCLC) patients is often considered as a terminal stage of advanced disease. Crizotinib is a small-molecule tyrosine kinase inhibitor (TKI) for ALK-rearranged NSCLC patients. Herein, we conducted a retrospective study to explore how Crizotinib affects the control of brain metastases and the overall prognosis in advanced ALK-rearranged NSCLC patients with brain metastases in Chinese population. A total of 34 patients were enrolled, of whom 20 (58.8%) patients had baseline brain metastases before Crizotinib treatment. Among patients with brain metastases before Crizotinib, overall survival (OS) after brain metastases was significantly longer than that of patients with brain metastases after Crizotinib (median OS, not reached vs. 10.3 months, respectively, p = 0.001). There was also a significant difference in systemic progression-free survival (PFS) between patients developing brain metastases before and after Crizotinib treatment (21.2 months vs. 13.9 months, p = 0.003). In conclusion, ALK-rearranged NSCLC patients with brain metastases before Crizotinib may benefit more from Crizotinib than those developing brain metastases during Crizotinib treatment.

// Tongtong Zhang 1, * , Qing Li 1, * , Shanshan Chen 1 , Yang Luo 1 , Ying Fan 1 and Binghe Xu 1 1 Department of Medical Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China * These authors have contributed equally to this work Correspondence to: Binghe Xu, email: bhxu@hotmail.com , xubinghe@medmail.com.cn Keywords: QLNC120, tyrosine kinase inhibitor, Phase I, HRAS Received: April 30, 2016 Accepted: November 09, 2016 Published: November 25, 2016 ABSTRACT This study evaluated the dose-limiting toxicities (DLT), maximum tolerated dose (MTD), pharmacokinetic profile, and preliminary antitumor activity of QLNC120, an inhibitor of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2), in HER2 overexpressing advanced breast cancer patients. In addition, the prognostic biomarkers of QLNC120 were investigated. QLNC120 was administered as a single dose, followed by 7 days observation, and then once daily consecutively. Scheduled dose escalation was 450mg, 750mg, 1000mg and 1250mg. For pharmacokinetic analysis, blood samples were collected after the single dose and after the first 7 days of continuous administration. Tissue samples were collected for biomarker analysis. Twenty-four heavily treated HER2 overexpressing advanced breast cancer patients were enrolled. No DLT was observed. MTD was not found. QLNC120 and its active metabolite-lapatinib exposure did not increase in a dose-dependent manner ranging from 450 to 1250mg QLNC120. From 450 to 1250mg QLNC120, the exposure of combination of QLNC120 and its active metabolite-lapatinib was equal to or greater than the exposure of 1250mg lapatinib. Common QLNC120-related toxicities included rash, diarrhea, oral mucositis, hematuria and white blood cell decrease. Seven of twenty-two evaluable patients achieved partial response (PR) or stable disease (SD)≥24 weeks. In biomarker analysis, nine of fifteen patients (60%) had a mutation in HRAS exon 1. Patients with HRAS mutation achieved longer progression free survival(PFS) (24.9 vs 12.9 weeks, p=0.023, HR=0.291). QLNC120 is well-tolerated and safe with encouraging antitumor activity in HER2 overexpressing advanced breast cancer. HRAS mutation was associated with the anti-tumor activity of QLNC120. (Trial registration: NCT01931943, http://ClinicalTrials.gov/show/NCT01931943 )

DC-10 is a distinct subset of human tolerogenic dendritic cells (DCs) which express high levels of human leukocyte antigen-G (HLA-G). DC-10 could induce adaptive type 1 regulatory T cells through the IL-10 dependent ILT4/HLA-G signaling pathway. However, the significance of DC-10 in malignancies remains unclear. In this study, the frequency and mean fluorescence intensity (MFI) of HLA-G+ DC-10 in the peripheral blood of 124 patients with gastric cancer (GC) and 130 normal controls was analyzed with flow cytometry. Plasma sHLA-G was analyzed with ELISA. Results showed both the percentages of peripheral HLA-G+ DC-10 (median: 0.13% vs 0.01%; p0.01) and MFI of HLA-G on these cells (median: 310.0 vs 91.5; p0.01) were dramatically increased in GC patients than in normal controls. The frequency of HLA-G+ DC-10 in GC patients was strongly relative to the tumor grade (p=0.021). sHLA-G levels in GC patients were significantly higher than in healthy controls (median: 85.80U/ml vs 61.20U/ml; p0.01). There was no significant correlation between the percentage of DC-10 and plasma sHLA-G (p0.05). However, the increased HLA-G+ DC-10, HLA-G MFI and plasma sHLA-G in patients with gastric cancer could be a diagnostic factor with the area under the ROC curve with 0.947 (p0.01), 0.882 (p0.01) and 0.700 (p0.01) respectively. Given the immune tolerant function of DC-10 could play, the increased DC-10 might play an important role in immune suppression for patients with gastric cancer, while more studies are necessary to illustrate the clinical relevance of DC-10 in cancer patients.

// Li Shang 1, * , Jia-Jie Hao 1, * , Xue-Ke Zhao 3, * , Jian-Zhong He 4, * , Zhi-Zhou Shi 1 , Hui-Juan Liu 5 , Li-Fei Wu 6 , Yan-Yi Jiang 1 , Feng Shi 1 , Hai Yang 1 , Yu Zhang 1 , Yi-Zhen Liu 1 , Tong-Tong Zhang 1 , Xin Xu 1 , Yan Cai 1 , Xue-Mei Jia 5 , Min Li 6 , Qi-Min Zhan 1 , En-Min Li 4 , Li-Dong Wang 3 , Wen-Qiang Wei 2 , Ming-Rong Wang 1 1 State Key Laboratory of Molecular Oncology, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100021, China 2 Department of Cancer Epidemiology, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100021, China 3 Henan Key Laboratory for Esophageal Cancer Research of the First Affiliated Hospital, Zhengzhou University, Zhengzhou 450000, China 4 Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou 515041, China 5 Department of Histology and Embryology, Anhui Medical University, Hefei 230032, China 6 Department of Gastroenterology, Anqing City Hospital, Affiliated Anqing Hospital of Anhui Medical University, Anqing 246003, China * These authors have contributed equally to this work Correspondence to: Ming-Rong Wang, e-mail: wangmr2015@126.com Wen-Qiang Wei, e-mail: weiwq@cicams.ac.cn Li-Dong Wang, e-mail: ldwang2007@126.com En-Min Li, e-mail: nmli@stu.edu.cn Keywords: ANO1, esophageal squamous cell carcinoma, precancerous lesions, biomarker, prognosis Received: September 17, 2015 Accepted: March 01, 2016 Published: March 21, 2016 ABSTRACT Objectives: Anoctamin 1 (ANO1) has been found to be overexpressed in esophageal squamous cell carcinoma (ESCC) in our previous study. Herein we showed the clinical relevance of ANO1 alterations with ESCC and esophageal precancerous lesion progression. Results: ANO1 was detected in 38.1% (109/286) and 25.4% (77/303) of tumors in the two cohorts, but in none of morphologically normal operative margin tissues. ANO1 expression was significantly associated with a shorter overall survival (OS), especially in patients with moderately differentiated and stage IIA tumors. In 499 iodine-unstained biopsies from the endoscopic screening cohort in 2005-2007, all the 72 pathologically normal epithelial mucosa presented negative immunostaining, whereas ANO1 expression was observed in 3/11 tumors and 5/231 intraepithelial lesions. 7/8 ANO1-positive cases had developed unfavorable outcomes revealed by endoscopic follow-up in 2012. Analysis of another independent cohort of 148 intraepithelial lesions further confirmed the correlation between ANO1 expression and progression of precancerous lesions. 3/4 intraepithelial lesions with ANO1 expression had developed ESCC within 4-9 years after the initial endoscopic examination. Methods: Immunohistochemistry (IHC) was performed to examine ANO1 expression in surgical ESCC specimens and two independent cohorts of esophageal biopsies from endoscopic screening in high-incidence area of ESCC in northern China. Association between ANO1 expression, clinico-pathologic parameters, and the impact on overall survival was analyzed. Conclusions: Positive ANO1 is a promising biomarker to predict the unfavorable outcome for ESCC patients. More importantly, it can predict disease progression of precancerous lesions.

The spinel oxides are identified as the highly promising materials for gas sensing application due to their good thermal stability, low cost and nice sensitivity. The spinel oxide nanocomposites of Co3O4/SnO2 and Co2SnO4/SnO2 were prepared by the co-precipitation method, and their gas sensing characteristics were investigated in this work. Compared with the Co3O4/SnO2 nanocomposites, the sensor based on Co2SnO4/SnO2 nanocomposites exhibited significantly enhanced response and selectivity performance toward triethylamine (TEA). The response of the Co2SnO4/SnO2 composites is about 45.9 to 100 ppm TEA at 270 °C, which was almost 4 times higher than that of Co3O4/SnO2 nanocomposites. The excellent performance of the Co2SnO4/SnO2 composites can be attributed to the catalytic ability of divalent Co2+ cation located in octahedral sites in spinel structure, which results in enhanced gas absorption and catalytic performance.

Background: Triple-negative breast cancer (TNBC) may be more sensitive to platinum-based regimens. This open-label, randomized phase III trial aimed to compare dose dense paclitaxel plus carboplatin (PCdd) with dose-dense epirubicin and cyclophosphamide followed by paclitaxel (ECdd-P) regimen as adjuvant chemotherapy (AC) for high-risk early TNBC. Methods: We included Chinese patients with high recurrence risk TNBC who underwent primary breast surgery. They were randomly assigned in a 1:1 ratio to receive PCdd (paclitaxel 150 mg/m2 on day 1 and carboplatin AUC=3 on day 2 for 8 cycles) or ECdd-P (epirubicin 80 mg/m2 divided in 2 days and cyclophosphamide 600 mg/m2 on day 1 for 4 cycles followed by paclitaxel 175 mg/m2 on day 1 for 4 cycles) every 2 weeks, with granulocyte colony-stimulating factor (G-CSF) support. The primary endpoint was 3-year disease-free survival (DFS); the secondary endpoints were overall survival (OS) and safety. Findings: The intent-to-treat population included 143 patients (70 in the PCdd arm and 73 in the ECdd-P arm). Compared with the ECdd-P arm, the PCdd arm had significantly higher 3-year DFS (93⋅9% vs.79⋅1%, hazard ratio[HR]=3⋅224, 95% confidence interval [CI] =1⋅420-7⋅321, log-rank p=0⋅0051) and OS (98⋅5% vs.92⋅9% [HR] =7⋅092, 95% CI=1⋅212-16⋅630, log-rank p=0⋅0281). The 3-year DFS in the PCdd arm was significantly higher (p 40 years, Ki-67>30, and clinically evaluated lymph nodes. Both regimens were well tolerated. Worse neutropenia (grade 3/4) was found in the ECdd-P arm (47⋅9% vs. 21⋅4%, p=0⋅001). Interpretation: PCdd was superior to ECdd-P as AC for early TNBC with respect to improving the 3-year DFS and OS. PCdd also yields lower hematological toxicity.Thus, PCdd might be a preferred AC regimen for early TNBC patients with high recurrence risk. Trial Registration: This trial is registered at ClinicalTrials. gov (number NCT01378533). Funding Statement: This study was supported by National Key Research and Development Program of China (2018YFC1312101); and Chinese Academy of Medical Science Initiative funded this study for Innovative Medicine (CAMS-12M-1-010). Declaration of Interests: All authors declare no conflicts of interest. Ethics Approval Statement: All interventions were performed in accordance with Chinese laws and regulations and the Helsinki declaration. The study protocol was approved by the independent ethics board committee at the National Cancer Center, Chinese Academy of Medical Sciences (Approval number: CH-BC-012).

In this article, a literature review about FGMs and a new idea were presented. In the past few years, the concept of FGMs has been introduced in the geotechnical engineering; some scholars have done some research about it. On this basis, this paper provided a new idea about the future application of FGMs in geotechnical engineering. The results show that the functionally gradient lining structure can meet the deformation requirement when the elastic modulus is reduced in some positions. In other words, the functionally gradient lining structure can reduce the material cost greatly.

Contactin 3 (CNTN3) is a member of the contactin family that is primarily expressed in the nervous system. However, to the best of our knowledge, expression of contactin and its role in the development and progression of brain tumours has not been studied. Although glioblastoma multiforme (GBM) is the most common malignant brain tumour, advances in therapeutic options for patients with GBM have been modest due to an incomplete understanding of the molecular mechanisms underlying development and progression. The aim of the present study was to examine the correlation between CNTN3 and its associated genes and the clinical outcome in patients with GBM. CNTN3 and the expression levels of associated genes were analysed in GBM datasets obtained from the SAGE Anatomical viewer website, Gene Expression Omnibus, Oncomine and The Cancer Genome Atlas. CNTN3 was significantly downregulated in patients with GBM. Subsequently, the expression of CNTN3 was further validated using immunohistochemistry in a cohort of GBM specimens. The immunohistochemistry results were consistent with the in silico analyses. Kaplan-Meier analysis indicated that patients with lower expression levels of CNTN3 had a significantly shorter overall survival (OS) time compared with patients with higher levels of CNTN3 expression. Univariate and multivariate Cox regression analyses demonstrated that CNTN3 expression was an independent prognostic indicator in patients with GBM. Furthermore, gene set enrichment analysis revealed that CNTN3 was associated with the receptor tyrosine-protein kinase (ErbB) signalling pathway. In the ErbB signalling pathway, epidermal growth factor receptor (EGFR) was negatively correlated with CNTN3. Taken together, these data suggest that lower expression levels of CNTN3 may be an independent biomarker that predicts poor OS time in patients with GBM, and that EGFR expression in the ErbB pathway may be associated with CNTN3 expression.

In order to investigate the effect of biochar on CH

Artesunate is one of artemisinin derivatives with anti-malarial and anti-inflammatory activities though its water solubility and bioavailability are low. Acute lung injury (ALI) is a seriously dispersive lung disease with a high mortality. In this study, artesunate liposomes were prepared with the film dispersion method, and then lyophilized to obtain the liposomal artesunate dry powder inhalers(LADPIs). The LADPIs were pulmonary-delivered into the lung to treat ALI in rats. The artesunate liposomes had the capsulation efficiency of 71.4%, the particle size of 47.3 nm, and the zeta potential of -13.7 m V. The LADPIs had the aerodynamic particle size of 4.2 μm and the fine particle fraction (FPF) of 34.5%. ALI was established in rats by instilling lipopolysaccharide (LPS) into the lungs. The rats quickly showed a reduction in movement and acceleration in breath followed by diarrhea and so on. The LADPIs were directly administrated into the lungs of ALI rats through airways after 1 h of LPS challenge. The treatment induced a reduction in ALI syndromes. Two inflammatory factors, including TNF-α and IL-6, were significantly reduced by the artesunate powder in the LADPI group similarly to the reduction in the positive drug dexamethasone group (P0.05). Therefore, the anti-inflammatory effect of LADPIs contributed to the anti-ALI activity. Furthermore, the liposomal formulation improved drug bioavailability in the lung and increased therapeutic efficiency. The LADPIs are promising medicines for therapy of ALI through local drug administration.

The long non-coding RNA (lncRNA) PVT1 plays vital roles in the tumorigenesis and development of various types of cancer. However, the potential expression profiling, functions and pathways of PVT1 in HCC remain unknown. PVT1 was knocked down in SMMC-7721 cells, and a miRNA microarray analysis was performed to detect the differentially expressed miRNAs. Twelve target prediction algorithms were used to predict the underlying targets of these differentially expressed miRNAs. Bioinformatics analysis was performed to explore the underlying functions, pathways and networks of the targeted genes. Furthermore, the relationship between PVT1 and the clinical parameters in HCC was confirmed based on the original data in the TCGA database. Among the differentially expressed miRNAs, the top two upregulated and downregulated miRNAs were selected for further analysis based on the false discovery rate (FDR), fold-change (FC) and P-values. Based on the TCGA database, PVT1 was obviously highly expressed in HCC, and a statistically higher PVT1 expression was found for sex (male), ethnicity (Asian) and pathological grade (G3+G4) compared to the control groups (P

Homeobox A1 (HOXA1) serves an oncogenic role in multiple cancer types. However, the role of HOXA1 in non-small cell lung cancer (NSCLC) remains unclear. In the present study, use of reverse transcription-quantitative polymerase chain reaction and the databases of The Cancer Genome Atlas (TCGA), Oncomine, Gene Expression Profiling Interactive Analysis and the Multi Experiment Matrix were combined to assess the expression of HOXA1 and its co-expressed genes in NSCLC. Bioinformatic analyses, such as Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and network and protein-protein interaction analyses, were used to investigate the underlying molecular mechanism effected by the co-expressed genes. Additionally, the potential miRNAs targeting HOXA1 were investigated. The results showed that HOXA1 was upregulated in NSCLC. The area under the curve of HOXA1 indicated a moderate diagnostic value of the HOXA1 level in NSCLC. According to GO and KEGG analyses, the co-expressed genes may be involved in 'dGTP metabolic processes', 'network-forming collagen trimers', 'centromeric DNA binding' and 'the p53 signaling pathway'. Three miRNAs (miR-181b-5p, miR-28-5p and miR-181d-5p) targeting HOXA1 were each predicted by 10 algorithms; miR-181b and miR-181d levels were downregulated in LUSC tissues compared with those in normal lung tissues based on data from the TCGA database, and inverse correlations were found between HOXA1 and miR-181b (r=−0.205, P

Background: This phase I/II clinical trial investigated S-1 administered with intensity-modulated radiotherapy (IMRT) as adjuvant therapy for node-positive gastric cancer. Patients had undergone radical resection and D1/D2 lymph node dissection. Methods: In phase I, patients received adjuvant chemoradiotherapy of IMRT (45 Gy in 25 fractions) with concurrent S-1 administered on a dose-escalation schedule to determine the recommended dose (RD). In phase II, the safety and efficacy of the RD of S-1 combined with IMRT were assessed. Results: We consecutively enrolled 73 patients (56 men; median age, 53 years; range, 29–73 years) and the phase I portion of the study included 27 patients. The RD of S-1 administered concomitantly with IMRT was 80 mg m−2 day−1 orally, twice daily. The phase II analysis included 52 patients (46 new patients plus 6 from phase I). 8 patients (15.4%) developed grade 3 or 4 toxicities. There were 21 recurrence events and 15 deaths (1 bowel obstruction, 14 gastric cancer). Three-year disease-free survival and overall survival were 62.2% (95% confidence interval (CI), 48.5–75.9) and 70.0% (95% CI, 56.3–83.7), respectively. The median time to recurrence was 17.5 months (range, 3.8–42.0). The median time from recurrence to death was 7.0 months (range, 1.5–28.7). Conclusions: S-1 combined with IMRT adjuvant chemoradiotherapy is safe and efficacious for advanced gastric cancer.

MicroRNAs have been reported to be involved in various biological processes. Here, we performed a systematic analysis to explore the clinical value and potential molecular mechanism of miR-145-5p in non-small cell lung cancer. First, a meta-analysis was performed with eligible literature, followed by microRNA microarrays in the Gene Expression Omnibus database, to verify the diagnostic and prognostic values of miR-145-5p. A cohort of 125 clinical paired non-small cell lung cancer samples was next used to detect the level of miR-145-5p and to explore the relationship of miR-145-5p with clinicopathological parameters. The Cancer Genome Atlas database was additionally applied to investigate the role of miR-145-5p in non-small cell lung cancer. The potential targets of miR-145-5p were predicted using 12 online prediction databases to explore the prospective molecular mechanism of miR-145-5p in non-small cell lung cancer. The expression of miR-145-5p in non-small cell lung cancer was significantly lower than that in healthy tissues. And miR-145-5p tended to show better diagnostic performance in lung squamous cell carcinoma than in lung adenocarcinoma. Furthermore, the expression of miR-145-5p was closely associated with lymph node metastasis in non-small cell lung cancer. Gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the target genes were mainly enriched with enzyme-linked receptor protein signaling pathways, SH3 domain binding, cell leading edge, and adherens junction. The protein–protein interaction network showed that eight hub genes (SMAD4, SMAD2, IRS1, FOXO1, ERBB4, NRAS, ACTB, and ACTG1) might be the key target genes of miR-145-5p in non-small cell lung cancer. The information we obtained might offer new perspectives for clinical diagnosis and treatment for non-small cell lung cancer.

BACKGROUND To date, no robust biomarkers have been available in clinical practice that can provide an early diagnostic evaluation of lung cancer. The objective of this study was to identify potential biomarkers for the early detection of lung cancer using bronchial brushing specimens. METHODS Immunocytochemistry was used to investigate the expression of 35 proteins in 880 bronchial brushing specimens from both outpatients and inpatients who had either lung cancer or benign lung lesions. An optimal panel was identified that had high sensitivity and considerable specificity for detecting lung cancer. Associations between protein expression and clinicopathologic parameters were assessed. RESULTS Tumor protein 53 (TP53), TP63, Ki67, epidermal growth factor receptor (EGFR), minichromosome maintenance complex component 6 (MCM6), MCM7, uncharacterized proteins KIAA1522 and KIAA0317, and ubiquitin-protein ligase UHR1 (ICBP90) frequently presented high expression in bronchial brushing specimens from patients who had lung cancer compared with patients who had benign lung lesions. A 6-protein panel consisting of TP53, Ki67, MCM6, MCM7, KIAA1522, and KIAA0317 was identified as the best combination, with sensitivity of 81.1% (309 of 381 specimens) for detecting nonsmall cell lung cancer (NSCLC) and 86.8% (145 of 167 specimens) for detecting small cell lung cancer (SCLC) (specificity, 83.3%; 65 of 78 specimens). The combination of cytology and the protein panel significantly improved the sensitivity of bronchial brushing examination for detecting lung cancer (P

DNAJB6 is a member of the heat shock protein 40 (Hsp40) family. We here investigated the clinical correlation and biological role of DNAJB6 overexpression in colorectal cancer (CRC). The expression of DNAJB6 protein was examined in 200 cases of colorectal adenocarcinomas by immunohistochemistry (IHC) technology. Gene transfection and RNA interference were performed to determine the effect of DNAJB6 expression on the invasion of CRC cells and to explore the underlying molecular mechanisms in vitro and in vivo. Overexpression of DNAJB6 was found in 39% (78/200) of the CRC tissues, especially in tumors at pT4 as compared with at pT1–3 (P = 0.02). A Kaplan–Meier survival analysis revealed a correlation between DNAJB6 expression and overall survival (OS) times (P = 0.003). Multivariate analysis confirmed that DNAJB6 overexpression was an independent prognostic factor for CRC (P = 0.002). RNA interference-mediated silencing of the DNAJB6 gene inhibited the invasion of CRC cells in vitro were accompanied by a significant reduction in the protein levels of IQ-domain GTPase-activating protein 1 (IQGAP1) and phosphorylated ERK (pERK). An in vivo assay showed that inhibition of DNAJB6 expression decreased the lung metastases of CRC cells. IHC analysis of serial sections showed that there was a positive correlation between DNAJB6 and IQGAP1 expression in primary CRC tissues (P = 0.013). The data suggest that DNAJB6 plays an important oncogenic role in CRC cell invasion by up-regulating IQGAP1 and activating the ERK signaling pathway and that DNAJB6 may be used as a prognostic marker for CRC. © 2014 Wiley Periodicals, Inc.

Recent industry research shows that the existing layout configuration can not satisfy complex manufacturing of many production types. New layout strategy, especially distributed layout received more attention, has the potential to cope with demand interference. This paper attempts to use the method of resource element (RE) to consider equipment production capacity to design weighted distributed layout. Give a more explicit description of unique and common processing ability of devices and parts processing requirements. Considering the weights between REs and make more relevant REs adjacent, using genetic algorithm to construct RE-based weighted distributed layout, minimizing the total weighted minimum distance between REs to minimize material transportation costs.

Two Zn(II) coordination polymers (CPs) [Zn(L)(pphda)] (1) and [Zn(L)(ophda)]&middot, H2O (2) were prepared by reactions of ZnSO4&middot, 7H2O based on the N-donor 1,4-di(1H-imidazol-4-yl)benzene (L) ligand and two flexible carboxylic acids isomers of 1,4-phenylenediacetic acid (H2pphda) and 1,2-phenylenediacetic acid (H2ophda) as mixed ligands, respectively. Structures of CPs 1 and 2 were characterized by elemental analysis, Infrared spectroscopy (IR), thermogravimetric analysis and single-crystal X-ray diffraction. The CP 1 is a fourfold interpenetrating 66-diamond (dia) architecture, while 2 is a 2D (4, 4) square lattice (sql) layer based on the Zn2(cis-1,2-ophda2&minus, )2 binuclear Zn(II) subunits. The luminescent property, including luminescence lifetime and quantum yield (QY), have been investigated for CPs 1 and 2.

528 Background: There are no well-established adjuvant chemotherapy (AC) regimens for early triple negative breast cancer (TNBC). Our randomized phase III trial was designed to compare dose dense paclitaxel plus carboplatin (PCdd) with commonly used dose dense epirubicin and cyclophosphamide, followed by paclitaxel (ECdd-T) regimen as AC for TNBC with high recurrence risk. Methods: Between May 2011 and November 2015, TNBC patients were randomized in 1:1 ratio to receive PCdd or ECdd-T regimen as AC every two weeks for 8 cycles with administration of granulocyte stimulating factor (G-CSF) support. The primary endpoint was 3-year disease free survival (DFS).The secondary endpoints included overall survival (OS) and safety. Survival analyses were also performed for different subgroups stratified by age status (≤40 years vs >40 years), Ki 67(40 years, clinically evaluated lymph nodes, TFS

Genomic aberration is a common feature of human cancers and also is one of the basic mechanisms that lead to overexpression of oncogenes and underexpression of tumor suppressor genes. Our study aims to identify frequent genomic changes and candidate copy number driving genes in esophageal squamous cell carcinoma (ESCC). We used array comparative genomic hybridization to identify recurrent genomic alterations and screened the candidate targets of selected amplification regions by quantitative and semi-quantitative RT-PCR. Thirty-four gains and 16 losses occurred in more than 50 % of ESCCs. High-level amplifications at 7p11.2, 8p12, 8q24.21, 11q13.2-q13.3, 12p11.21, 12q12 and homozygous deletions at 2q22.1, 8p23.1-p21.2, 9p21.3 and 14q11.2 were also identified. 11q13.2 was a frequent amplification region, in which five genes including CHKA, GAL, KIAA1394, LRP5 and PTPRCAP were overexpressed in tumor tissues than paracancerous normal tissues. The expression of ALG3 at 3q27.1 was higher in ESCCs, especially in patients with lymph node metastasis. Target gene identification of amplifications or homozygous deletions will help to reveal the mechanism of tumor formation and explore new therapy method.

To investigate whether endoplasmic reticulum (ER) stress participates in the neuroprotective effects of ischemic preconditioning (IPC)-induced neuroprotection and autophagy activation in rat brains.The right middle cerebral artery in SD rats was occluded for 10 min to induce focal cerebral IPC, and was occluded permanently 24 h later to induce permanent focal ischemia (PFI). ER stress inhibitor salubrinal (SAL) was injected via intracerebral ventricle infusion 10 min before the onset of IPC. Infarct volume and motor behavior deficits were examined after the ischemic insult. The protein levels of LC3, p62, HSP70, glucose-regulated protein 78 (GRP 78), p-eIF2α and caspase-12 in the ipsilateral cortex were analyzed using immunoblotting. LC3 expression pattern in the sections of ipsilateral cortex was observed with immunofluorescence.Pretreatment with SAL (150 pmol) abolished the neuroprotective effects of IPC, as evidenced by the significant increases in mortality, infarct volume and motor deficits after PFI. At the molecular levels, pretreatment with SAL (150 pmol) significantly increased p-eIF2α level, and decreased GRP78 level after PFI, suggesting that SAL effectively inhibited ER stress in the cortex. Furthermore, the pretreatment with SAL blocked the IPC-induced upregulation of LC3-II and downregulation of p62 in the cortex, thus inhibiting the activation of autophagy. Moreover,SAL blocked the upregulation of HSP70, but significantly increased the cleaved caspase-12 level, thus promoting ER stress-dependent apoptotic signaling in the cortex.ER stress-induced autophagy might contribute to the neuroprotective effect of brain ischemic preconditioning.

Our previous findings suggest that sphingosine kinase 2 (SPK2) mediates ischemic tolerance and autophagy in cerebral preconditioning. The aim of this study was to determine by which mechanism SPK2 activates autophagy in neural cells. In both primary murine cortical neurons and HT22 hippocampal neuronal cells, overexpression of SPK2 increased LC3II and enhanced the autophagy flux. SPK2 overexpression protected cortical neurons against oxygen glucose deprivation (OGD) injury, as evidenced by improvement of neuronal morphology, increased cell viability and reduced lactate dehydrogenase release. The inhibition of autophagy effectively suppressed the neuroprotective effect of SPK2. SPK2 overexpression reduced the co-immunoprecipitation of Beclin-1 and Bcl-2, while Beclin-1 knockdown inhibited SPK2-induced autophagy. Both co-immunoprecipitation and GST pull-down analysis suggest that SPK2 directly interacts with Bcl-2. SPK2 might interact to Bcl-2 in the cytoplasm. Notably, an SPK2 mutant with L219A substitution in its putative BH3 domain was not able to activate autophagy. A Tat peptide fused to an 18-amino acid peptide encompassing the native, but not the L219A mutated BH3 domain of SPK2 activated autophagy in neural cells. The Tat-SPK2 peptide also protected neurons against OGD injury through autophagy activation. These results suggest that SPK2 interacts with Bcl-2 via its BH3 domain, thereby dissociating it from Beclin-1 and activating autophagy. The observation that Tat-SPK2 peptide designed from the BH3 domain of SPK2 activates autophagy and protects neural cells against OGD injury suggest that this structure may provide the basis for a novel class of therapeutic agents against ischemic stroke.

Previous study showed that TIGAR (TP53-induced glycolysis and apoptosis regulator) protected ischemic brain injury via enhancing pentose phosphate pathway (PPP) flux and preserving mitochondria function. This study was aimed to study the role of TIGAR in cerebral preconditioning. The ischemic preconditioning (IPC) and isoflurane preconditioning (ISO) models were established in primary cultured cortical neurons and in mice. Both IPC and ISO increased TIGAR expression in cortical neurons. Preconditioning might upregulate TIGAR through SP1 transcription factor. Lentivirus mediated knockdown of TIGAR significantly abolished the ischemic tolerance induced by IPC and ISO. ISO also increased TIGAR in mouse cortex and hippocampus and alleviated subsequent brain ischemia-reperfusion injury, while the ischemic tolerance induced by ISO was eliminated with TIGAR knockdown in mouse brain. ISO increased the production of NADPH and glutathione (GSH) and scavenged reactive oxygen species (ROS), while TIGAR knockdown decreased GSH and NADPH production and increased the level of ROS. Supplementation of ROS scavenger NAC and PPP product NADPH effectively rescue the neuronal injury caused by TIGAR deficiency. Notably, TIGAR knockdown inhibited ISO-induced anti-apoptotic effects in cortical neurons. These results suggest that TIGAR participates in the cerebral preconditioning through reduction of ROS and subsequent cell apoptosis.

Purpose: To investigate the molecular mechanisms through which polo-like kinase-1 (PLK1) takes part in anoikis resistance of esophageal squamous cell carcinoma (ESCC) cells. Experimental Design: The role of PLK1 in cell anoikis resistance was examined by ectopic gene expression and siRNA-mediated knockdown. Glutathione S-transferase pull-down and co-immunoprecipitation assays were utilized to investigate PLK1-interacting proteins. Electrophoretic mobility shift assay, chromatin immunoprecipitation, and reporter gene assays were carried out to identify the transcription factors responsible for PLK1 expression during anoikis resistance. Results: We found that detachment of ESCC cells triggers the upregulation of PLK1. Elevated PLK1 expression contributes to protection against anoikis in cancer cells through the regulation of β-catenin expression. Moreover, we showed that, through direct binding to the PLK1 promoter, the NF-κB subunit RelA transcriptionally activates PLK1, which inhibits the ubiquitination and degradation of β-catenin. Inhibition of the NF-κB pathway restores the sensitivity of cancer cells to anoikis by downregulating PLK1/β-catenin expression. In addition, RelA gene amplification and protein overexpression was significantly correlated with PLK1 expression in ESCC tissues. Conclusions: Our findings suggest that upregulation of PLK1 triggered by cell detachment is regulated by RelA at the transcriptional level. PLK1 protects esophageal carcinoma cells from anoikis through modulation of β-catenin protein levels by inhibiting their degradation. Taken together, this study reveals critical mechanisms involved in the role of RelA/PLK1/β-catenin in anoikis resistance of ESCC cells. Clin Cancer Res; 17(13); 4285–95. ©2011 AACR.

The transcription factor Foxp3 plays a key role in CD4(+)CD25(+) regulatory T (Treg) cell function. A correlation has been shown between survival and the frequency of tumor-infiltrating Foxp3-positive Treg cells in cancer patients. However, few studies have characterized the regulation of Foxp3 expression and function in Treg cells, which are known to comprise distinct subsets, with different roles in the complex tumor microenvironment. Here, we show that significantly more Foxp3-positive Treg cells accumulated in gastric tumors. In addition, we found increased expression of Foxp3 protein per cell in tumor-infiltrating Treg cells. Moreover, elevated Foxp3 expression in tumor-infiltrating Treg cells was associated with the TNM stage in gastric cancer patients. Importantly, further investigation within the tumor microenvironment showed that expression of Foxp3 in Treg cells correlated with expression of cyclooxygenase-2 (COX-2) and prostaglandin E(2) (PGE(2)). Furthermore, Treg cells with higher levels of Foxp3 were able to suppress the proliferation of autologous CD4(+)CD25(-) T cells. The suppression of the effector T-cell response was reversed by COX inhibitors and PGE(2) receptor-specific antagonists. Our data demonstrate a mechanism by which tumor-infiltrating Treg cells with increased Foxp3 expression can mediate immune suppression via COX-2/PGE(2) production in the gastric cancer microenvironment. Thus, we provide new insights into overcoming regulatory T-cell activity, which may be beneficial for the treatment of human gastric cancer.

Exploration of mineral resources had been part of the major means to promote economic development in China, but the devastating effect of mining on the environment is inevitable. Based on the analysis of factors of the environmental disasters caused by the mining methods, this paper systematically analyzes the influences of open pit mining on land resource, ecological system, geological and ecological environment, especially analyzes the effects on the environment and ecological system. Meanwhile, the paper points out that the mining scale, method and type are the main factors that affect the environment and ecology. At the end of this paper, some rational countermeasures, protection and control measures for environmental protection and governance are put forward on the basis of the research.

Cell invasion and migration significantly contribute to tumor metastasis. Microtubule-associated protein 4 (MAP4) protein is one member of microtubule-associate proteins family. It is responsible for stabilization of microtubules by modulation of microtubule dynamics. However, there is little information about the involvement of MAP4 in human cancer. Here we show that MAP4 serves as a regulator of invasion and migration in esophageal squamous cancer cells. By activating the ERK-c-Jun-vascular endothelial growth factor A signaling pathway, MAP4 promotes cell invasion and migration in vitro, tumor growth and metastasis in mouse models. Immunohistochemical staining of operative tissues indicated that MAP4 expression was associated with tumor stage, lymph node metastasis and shorter survival of the patients with esophageal squamous cell carcinoma (ESCC). Multivariate Cox regression analysis showed that MAP4 is an independent prognostic indicator. In the serial sections of ESCC tissues, there was a positive correlation between MAP4 and vascular endothelial growth factor A expression. Notably, an intratumoral injection of MAP4-small interfering RNA (siRNA) remarkably inhibited the growth of the tumors that formed by the MAP4-expressing ESCC cells in nude mice, and a combination of MAP4-siRNA and Bevacizumab significantly enhanced the inhibition effect. Our data suggest that MAP4 is probably a useful prognostic biomarker and a potential therapeutic target for the disease.

Sixteen conventional heart beat variability (HRV) parameters and eight vital signs have shown promise in the prediction of cardiac arrest within 72 hours. Besides these 24 parameters, we proposed adding two new features for cardiac arrest prediction, which are approximate entropy (ApEn) and sample entropy (SpEn). ApEn and SpEn are nonlinear HRV parameters capable of characterizing heart conditions. These two entropies were derived from electrocardiography recordings and combined with the existing 24 features to form feature combinations. The experiments were conducted by using linear kernel Support Vector Machine classification technique to investigate the effects of using ApEn, SpEn together with 24 parameters on cardiac arrest prediction. The dimensionality reduction approach, Principal Component Analysis, was applied to suppress the dimensionality. Results reveal that the prediction performance of adding ApEn and SpEn to the 24 parameters is improved significantly compared to using the 24 parameters only. Dimension reduction has additional positive effects on improving the prediction results.

Background Our previous finding showed that brain ischemic preconditioning mediates neuroprotection through endoplasmic reticulum (ER) stress-induced autophagy. This study was aimed at exploring the role of ER chaperone GRP78 in IPC induced autophagy activation in neural cells. Results Ischemic preconditioning (IPC) and oxygen glucose deprivation (OGD) models were established in rat pheochromocytoma (PC12) cells and primary cultured murine cortical neurons. IPC exerted neuroprotection against subsequent OGD injury in both PC12 cells and primary cortical neurons. IPC increased GRP78 expression and activated autophagy, as evidenced by upregulated LC3 and Beclin1, increased autophagic flux and formation of autophagosomes. BAPTA(dibromo-1,2-bis(aminophenoxy)ethane N,N,N9,N9 - tetra acetic acid, 0.125-2 μM) and small interfering RNA targeted GRP78 abrogated IPC induced neuroprotection and decreased the expression of GRP78, LC3II/LC3I and Beclin1. In contrast, lentiviral vector mediated GRP78 overexpression (LV-GRP78) strengthened resistance of PC12 cells to OGD injury and increased LC3 and Beclin1 expression. Moreover, knockdown of GRP78 in stable GRP78 overexpressing PC12 cells abolished the upregulation of LC3II/LC3I. GRP78 might activate autophagy through AMPK - mTOR pathway. Conclusion These results suggest that IPC- induced GRP78 upregulation is involved in autophagy activation, and hence exerts protection against ischemic injury in neural cells. Electronic supplementary material The online version of this article (doi:10.1186/s13041-015-0112-3) contains supplementary material, which is available to authorized users.

An effective method is introduced to compensate for the mutual coupling effect in the estimation of signal parameter via rotational invariance techniques (ESPRIT) direction finding algorithm. The compensation method seeks to quantify the mutual coupling more accurately by using a new mutual impedance. Study of two closely spaced arriving signals shows that the high-resolution capability of ESPRIT can be achieved only when the mutual coupling effect is compensated for by using our new compensation method. Critical situations with a large signal level difference, with an increased mutual coupling effect resulting from a more compact-size antenna array, and with signals coming from a nonhorizontal elevation angle are also studied using the ESPRIT algorithm. Results show that the new compensation method, when applied to ESPRIT, is more accurate, more robust, and more flexible than the previous open-circuit voltage method.

To date, no robust biomarkers have been available in clinical practice that can provide an early diagnostic evaluation of lung cancer. The objective of this study was to identify potential biomarkers for the early detection of lung cancer using bronchial brushing specimens.Immunocytochemistry was used to investigate the expression of 35 proteins in 880 bronchial brushing specimens from both outpatients and inpatients who had either lung cancer or benign lung lesions. An optimal panel was identified that had high sensitivity and considerable specificity for detecting lung cancer. Associations between protein expression and clinicopathologic parameters were assessed.Tumor protein 53 (TP53), TP63, Ki67, epidermal growth factor receptor (EGFR), minichromosome maintenance complex component 6 (MCM6), MCM7, uncharacterized proteins KIAA1522 and KIAA0317, and ubiquitin-protein ligase UHR1 (ICBP90) frequently presented high expression in bronchial brushing specimens from patients who had lung cancer compared with patients who had benign lung lesions. A 6-protein panel consisting of TP53, Ki67, MCM6, MCM7, KIAA1522, and KIAA0317 was identified as the best combination, with sensitivity of 81.1% (309 of 381 specimens) for detecting nonsmall cell lung cancer (NSCLC) and 86.8% (145 of 167 specimens) for detecting small cell lung cancer (SCLC) (specificity, 83.3%; 65 of 78 specimens). The combination of cytology and the protein panel significantly improved the sensitivity of bronchial brushing examination for detecting lung cancer (P.00001), which increased from 49.1% to 81% in early stage NSCLC (stage I and II). In combined analyses, the protein panel was positively associated with patient sex (P=.00033), tumor type (P.00001), tumor location (P.00001), and lymph node metastasis (P=.028).The 6-protein panel is a potential biomarker for the early detection of lung cancer in bronchial brushings.

This paper analyzes the economic management category talents cultivation problem of colleges and universities in China, expounds the necessity and urgency of cultivate students' practical ability and innovation ability, sets the production management as an object, puts forward the basic train of thought for production management experimental teaching system, condenses the typical problem of production management in four dimensions. This paper discusses contents, principles of experiment teaching system for production management and functions which should be able to reflected in production management experiment projects, this work provides guidance and reference significance to construction and operation production management experiment system for colleges and universities. Introduction With the strengthening of social economy development and competition, society puts forward higher request to economic management class students’ knowledge structure, practical ability and comprehensive quality, especially students are required to have strong ability of combination theory with practice, application of learned knowledge. As one of the core curriculum of economic management major——production operation management is a course which theory and practice combined closely, but in the traditional classroom teaching mode, students’ hands-on skills are very poor, and because of a lack of practical experience, it’s difficult to really understand the related theory knowledge and digest after finished school study. Also, it’s difficult to quickly adapt to fast-paced, various actual job when get into social life for students. Traditionally, the main link students contact with actual——cognition practice, especially in professional practice, it’s unsustainable to continue the past practices. Because of relatively numerous of students, professional internship positions that companies can provide is limited. And based on the consideration of protecting commercial secrets, it is hard to contact with the internship substantial business for students. Therefore, the reform of the traditional teaching mode has become an important subject faced by class teaching. FUNG Y.(2010)discussed the relationship between the university laboratory and training the innovative talents, university laboratory building and opening up and the function of the laboratory in cultivating talents. Stefanovic M.(2013) thought the concept of laboratories for distance (e-learning) with remotely controlled laboratory set-ups or virtual laboratories with different simulations have an important role in industrial engineering education and training. Jiang Nanyun(2013) proposed the guidance problem (PBL), made students to apply the knowledge what they have learned of manufacturing operation management to solve work site layout, production site management, virtual reality simulation and production plan formulation practical problems etc. Jiang zengqiang(2013) put forward the thought of establish the relationship between experimental courses on the basis of hardware devices, MES as the main line and simulate the actual production site. Develop the industrial integration of engineering experiment. Fan Shuhai (2011) proposed an affordable VR 3 d reconstruction scheme for industrial engineering laboratory, selected hardware and software of each links, and described working process of the system. Zhen Yuqiao(2013) put a typical mechanical and electrical product as the research object, carried out trainings as product manufacturing organization 3rd International Conference on Science and Social Research (ICSSR 2014) © 2014. The authors Published by Atlantis Press 318 and management, product manufacturing process analysis and optimization, manufacturing system modeling simulation and optimization etc. In this article, the author thinks that it need to be set off from school talents cultivation orientation, typical the production operation management problems, reproduced tasks, processes, and work methods of enterprise production and operation environment in a laboratory environment, increase the intensity of experimental and practice teaching, training student's practical ability and innovation ability. In this paper, manufacturing management oriented talent cultivation as an example, discussed the construction of experiment teaching system for production management.

DNAJB6 is a member of the heat shock protein 40 (Hsp40) family. We here investigated the clinical correlation and biological role of DNAJB6 overexpression in colorectal cancer (CRC). The expression of DNAJB6 protein was examined in 200 cases of colorectal adenocarcinomas by immunohistochemistry (IHC) technology. Gene transfection and RNA interference were performed to determine the effect of DNAJB6 expression on the invasion of CRC cells and to explore the underlying molecular mechanisms in vitro and in vivo. Overexpression of DNAJB6 was found in 39% (78/200) of the CRC tissues, especially in tumors at pT4 as compared with at pT1-3 (P = 0.02). A Kaplan-Meier survival analysis revealed a correlation between DNAJB6 expression and overall survival (OS) times (P = 0.003). Multivariate analysis confirmed that DNAJB6 overexpression was an independent prognostic factor for CRC (P = 0.002). RNA interference-mediated silencing of the DNAJB6 gene inhibited the invasion of CRC cells in vitro were accompanied by a significant reduction in the protein levels of IQ-domain GTPase-activating protein 1 (IQGAP1) and phosphorylated ERK (pERK). An in vivo assay showed that inhibition of DNAJB6 expression decreased the lung metastases of CRC cells. IHC analysis of serial sections showed that there was a positive correlation between DNAJB6 and IQGAP1 expression in primary CRC tissues (P = 0.013). The data suggest that DNAJB6 plays an important oncogenic role in CRC cell invasion by up-regulating IQGAP1 and activating the ERK signaling pathway and that DNAJB6 may be used as a prognostic marker for CRC.

Background At present no objective parameters to identify the risk of liver metastasis after surgery have been established in rectal cancer. Objective To identify the chromosomal aberrations that are correlated with liver metastasis of rectal cancer. Methods Primary tumor tissues of rectal carcinoma were analyzed by array-based comparative genomic hybridization (array-CGH). Genomic aberrations were identified by Genomic Workbench and MD-SeeGH. Results The most frequent gains in rectal cancer were at 20q11.21-q13.33, 8q11.21-q24.3, 13q12.11-q14.2 and losses in 5q13.2, 8p23.3-p22, 17p13.3-p13.2 and 18q11.2-q23. Seven amplifications at 6p21.1, 8q24.21, 8q24.3, 13q13.2 and 20q13.2-q13.32 and nine homozygous deletions at 1q31.3, 4q12-q13.1, 4q32.3-q33, 5q13.2, 8p23.2, 8q11.23, 16p13.2, 19p13.11 and 19q13.41 were identified. Both frequency plot comparison and SAM (Significance analysis of microarray) methods indicated that losses at 1p35.3, 4p14, 14q23.1-q32.11 and 18p11.32-p11.21 were more frequent in patients without liver metastasis. Conclusions These liver metastasis associated genomic changes may be useful to reveal the mechanism of metastasis and identify candidate biomarkers.

Calreticulin (CRT) is a Ca2+-binding chaperone protein that alters cellular Ca2+-homeostasis in the endoplasmic reticulum (ER). Previously it was shown that CRT was overexpressed in esophageal squamous cell carcinoma (ESCC), and elevated CRT expression promoted the migration and invasion of ESCC cells. In the present study, the mechanisms underlying the role of CRT in esophageal carcinoma progression were investigated. Critically, depletion of CRT or protein-tyrosine phosphatase 1B (PTP1B) reduced ESCC cell migration and metastasis to the lung, whereas restoration of PTP1B protein levels rescued cell migration in CRT-silenced cells. Knockdown of CRT decreased PTP1B protein expression by reducing phosphorylation at the Y694 site of STAT5A, whereas knockdown of PTP1B reduced ERK1/2 phosphorylation at T204. Immunohistochemical analysis of CRT and PTP1B expression in ESCC patient tissues was strongly correlated. Importantly, PTP1B expression was associated with poor survival in patients with CRT overexpression. Overall, these data indicate a novel signaling pathway connecting CRT, STAT5A, PTP1B, and ERK1/2 in the regulation of ESCC cell migration. Implications: These findings suggest that PTP1B is a downstream effector of CRT signaling, promotes tumor progression, and can potentially be used as a new drug target for ESCC. Mol Cancer Res; 11(9); 986–94. ©2013 AACR.

The aim of the present study was to screen and identify the chromosomal aberrations that are correlated with clinicopathological characteristics of rectal cancer using array-based comparative genomic hybridization (array-CGH). Forty-eight fresh frozen tumor tissues of rectal carcinoma were analyzed by array-CGH. The results showed that most frequent gains included 8q24.3, 20q11.21-q13.32, 20q13.33 and losses in 8p23.3-p12, 17p13.1-p12 and 18q11.2-q23 were noted. Fourteen amplifications and seven homozygous deletions were identified in the rectal cancer samples. Losses of 4p16.1-p15.31, 8p21.1-p12 and gains of 7p12.3-p12.1 and 13q33.1-q34 were associated with positive lymph node status and advanced clinical stage (stages III and IV). The 17q24.2-25.3 gain was more frequent in patients with distant metastasis. Integrated analysis indicated that overexpression of PDP1, TRIB1, C13orf27, FOXA2, PMEPA1 and PHACTR3 was associated with gains, and underexpression of FHOD, SMAD4 and BCL2 was associated with losses. Pathway enrichment analysis showed that pathways of nitrogen metabolism, oxidative phosphorylation, cell cycle, maturity onset diabetes of young, cytokine-cytokine receptor interaction, MAPK signaling pathway and dentatorubropallidoluysian atrophy were influenced by copy number changes.