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1.
Front Public Health ; 10: 938113, 2022.
Article in English | MEDLINE | ID: mdl-35923964

ABSTRACT

Background: Artificial intelligence has far surpassed previous related technologies in image recognition and is increasingly used in medical image analysis. We aimed to explore the diagnostic accuracy of the models based on deep learning or radiomics for lung cancer staging. Methods: Studies were systematically reviewed using literature searches from PubMed, EMBASE, Web of Science, and Wanfang Database, according to PRISMA guidelines. Studies about the diagnostic accuracy of radiomics and deep learning, including the identifications of lung cancer, tumor types, malignant lung nodules and lymph node metastase, were included. After identifying the articles, the methodological quality was assessed using the QUADAS-2 checklist. We extracted the characteristic of each study; the sensitivity, specificity, and AUROC for lung cancer diagnosis were summarized for subgroup analysis. Results: The systematic review identified 19 eligible studies, of which 14 used radiomics models and 5 used deep learning models. The pooled AUROC of 7 studies to determine whether patients had lung cancer was 0.83 (95% CI 0.78-0.88). The pooled AUROC of 9 studies to determine whether patients had NSCLC was 0.78 (95% CI 0.73-0.83). The pooled AUROC of the 6 studies that determined patients had malignant lung nodules was 0.79 (95% CI 0.77-0.82). The pooled AUROC of the other 6 studies that determined whether patients had lymph node metastases was 0.74 (95% CI 0.66-0.82). Conclusion: The models based on deep learning or radiomics have the potential to improve diagnostic accuracy for lung cancer staging. Systematic Review Registration: https://inplasy.com/inplasy-2022-3-0167/, identifier: INPLASY202230167.


Subject(s)
Deep Learning , Lung Neoplasms , Artificial Intelligence , Humans , Lung/pathology , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/pathology , Neoplasm Staging
2.
Oncol Lett ; 14(6): 6690-6700, 2017 Dec.
Article in English | MEDLINE | ID: mdl-29163696

ABSTRACT

The aim of the present study was to investigate the effectiveness of 125I particle implantation during R2resection for non-small cell lung cancer (NSCLC). Data from 23 patients with NSCLC and macroscopic residual diseasefollowing surgery (R2 resection) between March 2010 and May 2014 were retrospectively analyzed. Among these patients, 12 patients [4 with T-residual disease (incomplete resection of primary tumor but complete dissection of regional lymph node), 8 with N-residual disease (complete resection of primary tumor but incomplete resection of metastatic regional lymph node)] underwent 125I particle implantation during the operation, while the other 11 (4 with T-residual disease and 7 with N-residual disease) received postoperative conventional radiotherapy. The local control rate, overall survival, and distant metastasis were evaluated. Additionally, the efficacy and safety of brachytherapy using 125I particle implantation during surgery for locally advanced NSCLC were investigated. The 23 patients were followed up for 3-40 months. For the 125I group, the 2-year local control rate was 100%, and the median survival time was 24 months. The 1-2-year survival rates were 83.3 and 58.33%, respectively. For the postoperative radiotherapy group, the median survival time was 12 months, andthe 1- and 2-year survival rates were 54.5 and 27.7%, respectively. No statistically significant difference in 2-year survival rates was detected between the two treatment groups, but the particle implantation group exhibited a higher survival rate trend. For patients with T-residual disease, the survival rate was higher for the 125I seed implantation group compared with the postoperative radiotherapy group. However, there was no significant difference in the rates of metastasis between the two groups for patients with N-residual disease. Therefore, intraoperative implantation of 125I particles during R2 resection of NSCLC may be a safer and more reliable method to reduce the local recurrence rate compared with conventional radiotherapy. Although not statistically significant, the overall survival rate of patients in the 125I seed implantation group was higher compared with the postoperative radiotherapy group.

3.
Radiat Oncol ; 11(1): 119, 2016 Sep 13.
Article in English | MEDLINE | ID: mdl-27623620

ABSTRACT

BACKGROUND: Recurrent or metastatic lung cancer is difficult to manage. This retrospective study aimed to assess the efficacy of repeated iodine-125 seed implantations combined with external beam radiotherapy (EBRT) for locally recurrent or metastatic stage-III/IV non-small cell lung cancer (NSCLC). METHODS: Eighteen previously treated stage-III/IV NSCLC patients with local or metastatic recurrences underwent 1-to-3 iodine-125 implantations. Six of these patients received palliative EBRT and six patients received combined chemotherapy using gemcitabine and cisplatin. Near-term treatment efficacy was evaluated 3 months after seed implantation by comparing changes in tumor size on computed tomography images; the evaluated outcomes were complete response, partial response, stable disease, and local tumor control rate. Long-term efficacy was assessed based on 1- and 2-year survival rates. RESULTS: Patients were followed up for 6 to 50 months. The overall (i.e., complete + partial) response rate was 87.4 %. The local control rates after the first, second, and third years were 94.1, 58.8 and 41.2 %, respectively. CONCLUSIONS: The results of this study demonstrated that repeated implantation of radioactive particles combined with EBRT is a safe treatment that effectively controlled local recurrence and metastasis of stage III/IV NSCLC.


Subject(s)
Carcinoma, Non-Small-Cell Lung/radiotherapy , Iodine Radioisotopes/therapeutic use , Lung Neoplasms/radiotherapy , Radiotherapy/methods , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Brachytherapy/methods , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/pathology , Cisplatin/administration & dosage , Combined Modality Therapy/methods , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Female , Humans , Lung Neoplasms/drug therapy , Male , Middle Aged , Neoplasm Metastasis , Neoplasm Recurrence, Local , Radiotherapy Dosage , Remission Induction , Retrospective Studies , Treatment Outcome , Gemcitabine
4.
J Cancer Res Ther ; 12(1): 121-5, 2016.
Article in English | MEDLINE | ID: mdl-27072223

ABSTRACT

PURPOSE: Here we aimed to explore the possible mechanism and potential regulatory relationships in which the non.small.cell lung cancer. (NSCLC)-resisted epidermal growth factor receptor. (EGFR) tyrosine kinase inhibitor erlotinib. MATERIALS AND METHODS: GSE38310, the gene expression profiles of NSCLC cell lines treated with dimethylsulfoxide or erlotinib, including HCC827, ER3, and T15-2, were downloaded from Gene Expression Omnibus database and preprocessed by normalization. Basing on the regulatory relationships of transcriptional factors obtained from University of California Santa Cruz. (UCSC) database, the differentially expressed genes. (DEGs) were screened using limma package in R with. |logFC| >1 and P < 0.05, and regulatory networks of these DEGs were built with supervised inference of regulatory networks (SIRENE). Subsequently, differentially regulatory networks were compared basing on Limit Fold Change. (LFC) method. RESULTS: Totally 24,380 genes were obtained, 1,531 DEGs were identified in HCC827 cell lines, 37 DEGs in ER3 cell lines, 156 DEGs in T15-2 cell lines. After removing the redundancy genes, 1,575 differentially expressed genes were got at last. Basing on three regulatory networks of HCC827 cell lines, ER3 cell lines and T15-2 cell lies, sex-determining region Y (SRY).related high mobility group-box gene 9. (SOX9) and Suppressor of cytokine signaling 3 (STAT3) were identified by comparing with HCC827 and ER3 networks. And suppressor of cytokine signaling 5 B (STAT5B), early growth response-1 (EGR1) and STAT6 were obtained in comparison of HCC827 and T15-2 networks. CONCLUSIONS: The regulatory edges with remarkable changes between HCC827 and ER3, HCC827 and T15.2 included some transcription factors and genes. (e. g., STAT3 and SOX9). STAT3, SOX9, STAT5B, EGR1, and STAT6 might affect the resistance of NSCLC to erlotinib.


Subject(s)
Antineoplastic Agents/administration & dosage , Carcinoma, Non-Small-Cell Lung/drug therapy , Drug Resistance, Neoplasm/genetics , Erlotinib Hydrochloride/administration & dosage , Neoplasm Proteins/genetics , Protein Kinase Inhibitors/administration & dosage , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Cell Line, Tumor , Early Growth Response Protein 1/biosynthesis , ErbB Receptors/antagonists & inhibitors , ErbB Receptors/genetics , Gene Expression Regulation, Neoplastic/drug effects , Humans , Mutation , Neoplasm Proteins/biosynthesis , SOX9 Transcription Factor/biosynthesis , STAT3 Transcription Factor/biosynthesis , STAT5 Transcription Factor/biosynthesis , STAT6 Transcription Factor/biosynthesis , Signal Transduction/drug effects
5.
Brain Inj ; 29(7-8): 981-8, 2015.
Article in English | MEDLINE | ID: mdl-25915805

ABSTRACT

PRIMARY OBJECTIVE: To investigate the epidemiology of TBI in Chinese inpatients. RESEARCH DESIGN: Civilian inpatients of Chinese military hospitals diagnosed with TBI between 2001-2007 were identified using ICD-9-CM codes. METHODS AND PROCEDURES: Demographic characteristics, admission time, injury cause, injury severity, length of stay and outcomes were compared between ICD-9-CM diagnosis groups. MAIN OUTCOMES AND RESULTS: In total, 203 553 civilian patients with TBI (74.86% male, 25.14% female) were identified from >200 Chinese military hospitals. TBI diagnoses increased by a mean of 4.67% each year. Admission peaked during the third quarter of the year and October annually. The leading causes of TBI were motor vehicle-traffic (51.41%), falls (21.49%) and assaults (15.77%). TBI was categorized by abbreviated injury scale score as mild in 36.64%, serious in 20.13%, severe in 26.81% and critical in 15.68% of inpatients. The mean length of stay was 17.8 ± 24.1 days. Recovery rate was 93.06% and mortality was 4.14%. CONCLUSIONS: The epidemiological data may contribute to the development of effective, targeted strategies to prevent TBI.


Subject(s)
Accidental Falls/statistics & numerical data , Accidents, Traffic/statistics & numerical data , Brain Injuries/epidemiology , Hospitals, Military/statistics & numerical data , Length of Stay/statistics & numerical data , Violence/statistics & numerical data , Adolescent , Adult , Age Distribution , Brain Injuries/etiology , Child , China/epidemiology , Female , Glasgow Coma Scale , Hospitalization , Humans , Injury Severity Score , Male , Middle Aged , Sex Distribution
6.
Mol Med Rep ; 11(6): 4291-6, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25634618

ABSTRACT

The present study aimed to evaluate the effects of p28GANK expression on the metastasis of oesophageal squamous cell carcinoma (ESCC) tissues and to investigate its roles in the metastasis of highly invasive and non­invasive ESCC cell lines. Quantitative polymerase chain reaction (qPCR) and immunohistochemical analyses were performed to assess p28GANK mRNA and protein expression in ESCC tissues and to analyse its significance in ESCC metastasis. qPCR and western blot analyses were used to detect p28GANK mRNA and protein expression in highly invasive and non­invasive cell lines. Subsequently, lentivirus­mediated p28GANK short interfering RNA (siRNA) was transfected into highly invasive ESCC cells, and Transwell assays were performed to analyse the effects of p28GANK knockdown on their migration and invasion. The mean expression levels of p28GANK mRNA in the ESCC tissues of patients with metastasis were significantly higher than those in the ESCC specimens from patients without metastasis. p28GANK expression in ESCC tissues was correlated with T­stage, lymph node metastasis and lymphatic invasion. The mRNA and protein expression levels of p28GANK were significantly higher in highly invasive cell lines compared with those of matched, non­invasive cell lines. Lentivirus­mediated siRNA knockdown of p28GANK markedly decreased p28GANK expression in EC109­P and EC9706­P cells and supressed the metastasis of ESCC cells in vitro. In conclusion, p28GANK expression was increased in metastatic ESCC tissues and cells, and p28GANK knockdown decreased the metastatic ability of ESCC cells. These results suggested that p28GANK may be a potential therapeutic marker for ESCC metastasis.


Subject(s)
Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/pathology , Esophageal Neoplasms/genetics , Esophageal Neoplasms/pathology , Gene Expression , Proteasome Endopeptidase Complex/genetics , Proto-Oncogene Proteins/genetics , Adult , Aged , Carcinoma, Squamous Cell/metabolism , Cell Line, Tumor , Cell Movement/genetics , Esophageal Neoplasms/metabolism , Esophageal Squamous Cell Carcinoma , Female , Gene Knockdown Techniques , Humans , Immunohistochemistry , Male , Middle Aged , Neoplasm Metastasis , Neoplasm Staging , Proteasome Endopeptidase Complex/metabolism , Proto-Oncogene Proteins/metabolism , RNA Interference
7.
J Cancer Res Clin Oncol ; 141(5): 785-95, 2015 May.
Article in English | MEDLINE | ID: mdl-25342326

ABSTRACT

PURPOSES: Uncontrolled proliferation is a key characteristic of gastric carcinogenesis and the precise mechanisms underlying the altered proliferation behaviors of GC cells have not been clearly elucidated. miRNAs has been suggested to play a crucial role in the pathogenesis and development of various cancers. In the present study, we employed an impedance-based real-time cell electronic sensing (RT-CES) system to detect the effects of ectopically expressed miRNAs on GC cell proliferation. METHODS: miRNA mimics were transfected into gastric cancer cell line SGC7901 and the effect of individual miRNA on the proliferation rate of the cells was measured by the RT-CES system. The screening results were validated with qRT-PCR and miR-137 was selected for further research. The effects of ectopically expressed miR-137 on GC cell growth and cell cycle progress were measured using MTT assay and flow cytometry. The target gene of miR-137 was predicted using different bioinformatics tools and the direct interaction between miR-137 and the 3'-UTR was confirmed with a luciferase reporter assay. The in vivo effect of miR-137 on GC cell proliferation was examined with a tumor-bearing nude mouse model. The correlation between miR-137 expression and patients' prognosis was explored in a cohort of 38 patients. Prognosis was explored in a cohort of 38 patients. RESULTS: Ectopic expression of miR-137 was sufficient to inhibit GC cell proliferation both in vitro and in vivo. Bioinformatics prediction and luciferase reporter assay revealed CDK6 as a target gene through which miR-137 exerted an inhibitory function. Moreover, miR-137 expression positively correlated with better prognosis. CONCLUSION: Our data indicated an important regulatory role of miR-137 in GC cell proliferation and that it may be explored as a prognostic marker for GC.


Subject(s)
Cell Proliferation , Cyclin-Dependent Kinase 6/genetics , MicroRNAs/metabolism , Stomach Neoplasms/metabolism , Stomach Neoplasms/pathology , Aged , Animals , Apoptosis , Blotting, Western , Cell Cycle , Cell Line, Tumor , Cyclin-Dependent Kinase 6/metabolism , Female , Flow Cytometry , Gene Expression Regulation, Neoplastic , Heterografts , Humans , Lymphatic Metastasis , Male , Mice , Middle Aged , Neoplasm Staging , Prognosis , Real-Time Polymerase Chain Reaction , Up-Regulation
8.
Med Oncol ; 32(1): 395, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25428394

ABSTRACT

This study compared the efficacy of iodine-125 seed brachytherapy versus the conventional radiotherapy in patients with non-resectable stage III/IV non-small cell lung cancer. A total of 71 patients with inoperable advanced stages of lung cancer with tumor size ranging 5-10 cm were randomly assigned into two groups: Group A received the regional iodine-125 implantation (n = 35), and Group B received the conventional radiotherapy (n = 36). The isodose curves were obtained by the treatment planning system for patients in Group A. Postoperative tumor size, clinical symptoms, and quality of life were then assessed. The overall response rate (complete response + partial response) was 88 and 59 % in Group A and Group B, respectively. Moreover, patients receiving iodine-125 implantation had higher one- or two-year survival rates than those patients receiving radiation therapy (P < 0.05). For patients with a large tumor, iodine-125 implantation significantly ameliorated the clinical symptoms and improved quality of life compared with the conventional radiotherapy and chemotherapy. Iodine-125 implantation treatment was more effective to control inoperable, large lung cancer and improved overall survival and quality of life compared with the conventional radiotherapy and chemotherapy.


Subject(s)
Brachytherapy/methods , Carcinoma, Non-Small-Cell Lung/radiotherapy , Iodine Radioisotopes/therapeutic use , Lung Neoplasms/radiotherapy , Adult , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/mortality , Female , Humans , Kaplan-Meier Estimate , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Staging , Radiotherapy/methods
9.
Exp Ther Med ; 7(6): 1578-1582, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24926347

ABSTRACT

The aim of the present study was to investigate the correlation between the expression levels of excision repair cross complementing 1 (ERCC1), thymidylate synthase (TYMS), class III ß-tubulin (TUBB3), ribonucleoside-diphosphate reductase (RRM1) and topoisomerase IIα (TOP2A) with the clinical characteristics of patients with esophageal squamous cell carcinoma (ESCC). A total of 29 ESCC tissue samples were collected from patients that had not previously received systematic treatment. The expression levels of ERCC1, TYMS, TUBB3, RRM1 and TOP2A were determined using a microarray technique, while Spearman's rank correlation analysis was used to determine the strength of the correlations between the expression levels of the biomarkers and the pathogenesis of esophageal cancer. High expression levels of TYMS and TOP2A were observed in 24% of the samples and high expression levels of TUBB3 and RRM1 were identified in 7% of the samples. Hierarchical clustering analysis of these biomarkers enabled the samples to be grouped. Group 1 patients exhibited low expression levels of TYMS, RRM1 and TOP2A and high expression of ERCC1 and TUBB3, while group 2 samples had low expression levels of ERCC1 and TUBB3 and high expression levels of TYMS, RRM1 and TOP2A. Analysis using Fisher's exact test demonstrated a statistically significant difference in the severity of carcinoma invasion between the two groups (P<0.05), however, no significant differences were identified with regard to the clinical stage or lymphatic metastasis (P>0.05). Therefore, hierarchical clustering analysis indicated that the expression levels of ERCC1, TYMS, TUBB3, RRM1 and TOP2A were closely associated with the clinical characteristics of patients with ESCC.

10.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 30(4): 411-3, 2014 Apr.
Article in Chinese | MEDLINE | ID: mdl-24721411

ABSTRACT

OBJECTIVE: To analyze the significance of sterile alpha motif domain-containing 9 (SAMD9) expression in esophageal squamous cell carcinoma (ESCC). METHODS: Immunohistochemical staining was performed to detect the expression of SAMD9 in 72 primary ESCC and matched adjacent cancer-free tissues and analyze the significance of SAMD9 expression in ESCC tissues. In addition, Western blotting was used to detect the expression of SAMD9 in primary ESCC tissues which were taken from 3 metastatic and 3 non-metastatic patients during surgery. RESULTS: The expression of SAMD9 in the ESCC tissues had no statistical difference from that in the matched adjacent cancer-free tissues. SAMD9 expression was significantly correlated with lymphatic invasion and metastasis in these patients (P<0.05), but not with age, gender, tumor differentiation and T stage (P>0.05). Western blotting showed that SAMD9 expression in primary ESCC tissues was significantly higher in the patients with metastasis than in the ones without metastasis(P<0.01). CONCLUSION: Over-expression of SAMD9 is correlated with the metastasis of ESCC, indicating that it might play an important role in the metastasis of ESCC.


Subject(s)
Carcinoma, Squamous Cell/metabolism , Esophageal Neoplasms/metabolism , Gene Expression Regulation, Neoplastic , Proteins/metabolism , Adult , Aged , Carcinoma, Squamous Cell/pathology , Esophageal Neoplasms/pathology , Female , Humans , Intracellular Signaling Peptides and Proteins , Male , Middle Aged , Neoplasm Metastasis
11.
J Med Case Rep ; 7: 211, 2013 Aug 23.
Article in English | MEDLINE | ID: mdl-23972148

ABSTRACT

INTRODUCTION: There have been no reports in the literature of esophageal rupture in adults resulting from an explosion of an automobile tire. We report the first case of just such an occurrence after an individual bit into a tire, causing it to explode in his mouth. CASE PRESENTATION: A 47-year-old Han Chinese man presented with massive hemorrhage in his left eye after he accidentally bit an automobile tire tube which burst into his mouth. He was diagnosed with esophageal rupture based on a chest computed tomography scan and barium swallow examination. Drainage of empyema (right chest), removal of thoracic esophagus, exposure of cervical esophagus, cardiac ligation and gastrostomy were performed respectively. After that, esophagogastrostomy was performed. CONCLUSIONS: Successful anastomosis was obtained at the neck with no postoperative complications 3 months after the surgery. The patient was discharged with satisfactory outcomes. We present this case report to bring attention to esophageal rupture in adults during the explosion of an automobile tire tube in the mouth.

12.
PLoS One ; 8(1): e52184, 2013.
Article in English | MEDLINE | ID: mdl-23341893

ABSTRACT

BACKGROUND: The major reason for the poor prognosis of esophageal squamous cell carcinoma (ESCC) patients is lymph node (LN) metastases. METHODOLOGY/PRINCIPAL: In the present study, gene expression profiling assay (GEP) was performed to identify the differences in gene expression profiles between primary ESCC tumors that were with LN metastases (N(+)) and those without LN metastases (N(-)). CONCLUSIONS/SIGNIFICANCE: A total of 23 genes were identified as being significantly elevated, and 30 genes were sharply decreased in ESCC tumors that were N(+) compared with N- tumors. Among these genes, two transcripts of the short chain dehydrogenase/reductase family 9C, member 7 (SDR9C7) were observed 7 times more frequently in N(+) compared with N(-) tumors. Immunohistochemical staining showed that SDR9C7 expression closely correlated with metastasis, and would be a prognostic marker for ESCC patients. To investigate the role of SDR9C7 in the ESCC metastasis, repeated transwell assays were adopted to establish highly and non-invasive ESCC sublines, and western blot showed that SDR9C7 expression was markedly higher in highly invasive cells compared with non-invasive ones. Down-regulation of SDR9C7 dramatically inhibited the metastatic abilities in vitro and in vivo, and repressed the expression of MMP11 in highly invasive cells, indicating that SDR9C7 promotes ESCC metastasis partly through regulation of MMP11, and might be a potential prognostic and therapeutic marker for ESCC patients.


Subject(s)
Carcinoma, Squamous Cell/enzymology , Carcinoma, Squamous Cell/pathology , Esophageal Neoplasms/enzymology , Esophageal Neoplasms/pathology , Lymphatic Metastasis/pathology , Oxidoreductases/metabolism , Adult , Aged , Animals , Blotting, Western , Carcinoma, Squamous Cell/genetics , Cell Line, Tumor , Down-Regulation/genetics , Esophageal Neoplasms/genetics , Esophageal Squamous Cell Carcinoma , Female , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Gene Knockdown Techniques , Humans , Immunohistochemistry , Lentivirus/metabolism , Lymphatic Metastasis/genetics , Male , Mice , Middle Aged , Multivariate Analysis , Neoplasm Invasiveness , Oxidoreductases/genetics , Prognosis , RNA, Messenger/genetics , RNA, Messenger/metabolism , RNA, Small Interfering/metabolism , Up-Regulation/genetics
13.
PLoS One ; 7(10): e41693, 2012.
Article in English | MEDLINE | ID: mdl-23144691

ABSTRACT

An increasing body of evidence indicates that miR-149 can both suppress and promote tumor growth depending on the tumor type. However, the role of miR-149 in the progression of gastric cancer (GC) remains unknown. Here we report that miR-149 is a tumor suppressor in human gastric cancer. miR-149 expression is decreased in GC cell lines and clinical specimens in comparison to normal gastric epithelial cell and tissues, respectively. The expression levels of miR-149 also correlate with the differentiation degree of GC cells and tissues. Moreover, ectopic expression of miR-149 in gastric cancer cells inhibits proliferation and cell cycle progression by down-regulating ZBTB2, a potent repressor of the ARF-HDM2-p53-p21 pathway, with a potential binding site for miR-149 in its mRNA's 3'UTR. It is also found that ZBTB2 expression increases in GC cells and tissues compared to normal gastric epithelial cell and tissues, respectively. Silencing of ZBTB2 leads to suppression of cell growth and cell cycle arrest in G0/G1 phase, indicating that ZBTB2 may act as an oncogene in GC. Furthermore, transfection of miR-149 mimics into gastric cancer cells induces down-regulation of ZBTB2 and HDM2, and up-regulation of ARF, p53, and p21 compared to the controls. In summary, our data suggest that miR-149 functions as a tumor suppressor in human gastric cancer by, at least partially through, targeting ZBTB2.


Subject(s)
Cell Cycle Checkpoints/genetics , Cell Proliferation , MicroRNAs/genetics , Repressor Proteins/genetics , Stomach Neoplasms/genetics , 3' Untranslated Regions/genetics , Base Sequence , Binding Sites/genetics , Blotting, Western , Cell Line , Cell Line, Tumor , Down-Regulation , G1 Phase/genetics , Gene Expression Regulation, Neoplastic , Humans , Immunohistochemistry , MicroRNAs/metabolism , Mutation , Repressor Proteins/metabolism , Resting Phase, Cell Cycle/genetics , Reverse Transcriptase Polymerase Chain Reaction , Stomach Neoplasms/metabolism , Stomach Neoplasms/pathology
14.
Cancer Biol Ther ; 13(8): 606-13, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22441818

ABSTRACT

Twist-1 protein (also called Twist) has been suggested to be involved in tumor epithelial-mesenchymal transition (EMT) related progression, however, the mechanism by which twist promotes lymph node metastasis is not fully understood. In the present study, we found that nuclear twist expression is clearly correlated with lymph node (LN) metastasis as determined by immunohistochemistry (IHC). A highly invasive EC109 cell subline, EC109-P, was established by repeated in vitro transwell isolations for the cell model. Immunofluorescence (IF) assay demonstrated that nuclear twist expression was markedly higher in the highly invasive EC109-P cell line when compared with EC109 and EC9706 cells. Based on our cell model, the function and mechanism by which twist regulates LN metastasis in ESCC was investigated. The results showed that the overexpression of Twist could significantly increase the invasion and VEGF-C expression of EC9706 cells, whereas the knockdown of twist expression results in the opposite effects. This finding was further strengthened by the results of the analysis of co-expression of twist and VEGF-C by IHC in ESCC clinical samples. In summary, our study indicates that nuclear twist plays an important role in ESCC lymphatic metastasis by increasing the expression of VEGF-C. The combination of twist and VEGF-C detection could be a reliable prediction of LN metastasis in ESCC.


Subject(s)
Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/pathology , Cell Nucleus/metabolism , Esophageal Neoplasms/metabolism , Esophageal Neoplasms/pathology , Twist-Related Protein 1/metabolism , Adult , Aged , Carcinoma, Squamous Cell/genetics , Cell Nucleus/genetics , Esophageal Neoplasms/genetics , Female , Gene Expression Regulation, Neoplastic , Humans , Lymph Nodes/metabolism , Lymph Nodes/pathology , Male , Middle Aged , Neoplasm Invasiveness/genetics , Neoplasm Metastasis/genetics , Twist-Related Protein 1/genetics , Vascular Endothelial Growth Factor C/genetics , Vascular Endothelial Growth Factor C/metabolism
15.
Dig Dis Sci ; 55(12): 3408-14, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20411424

ABSTRACT

BACKGROUND: CIAPIN1, a newly identified antiapoptotic molecule, is a downstream effector of the receptor tyrosine kinase-Ras signaling pathway in the mouse Ba/F3 pro-B cell line. Neither CIAPIN1 expression nor its clinical significance has been previously examined in esophageal squamous cell carcinoma (ESCC), and the present immunohistochemical analysis is the first study on CIAPIN1 distribution in ESCC. AIMS: To investigate the relationships between the expression of CIAPIN1 and clinicopathological characteristics of ESCC, and evaluate the relationship between the expression of this gene and prognosis in ESCC patients. METHODS: The expression of CIAPIN1 was investigated in 112 surgically resected specimens of ESCC by immunohistochemistry using a specific monoclonal antibody. The relations of CIAPIN1 expression with clinicopathological characteristics and the postoperative survival rate were statistically analyzed. RESULTS: We found that the expression of CIAPIN1 was statistically correlated with the degree of differentiation, depth of invasion, and lymph node metastasis of ESCC. Consistently, the survival rates of patients with CIAPIN1-negative tumors tended to be statistically lower than those with CIAPIN1-positive tumors. However, no significant difference was observed between CIAPIN1 expression and the patient age, sex, tumor location, and distant metastasis. Furthermore, multivariate analysis was performed by using Cox's proportional hazards model, and the results showed that lymph node metastases and CIAPIN1 expression were two independent prognostic factors. CONCLUSIONS: CIAPIN1 might play an important role in esophageal carcinogenesis, and it could be considered as a valuable prognostic indicator in ESCC. Finally, functional enhancement of CIAPIN1 might lead to a novel strategy for the treatment of SCC in the esophagus.


Subject(s)
Carcinoma, Squamous Cell/metabolism , Esophageal Neoplasms/metabolism , Gene Expression Regulation, Neoplastic/physiology , Intracellular Signaling Peptides and Proteins/metabolism , Aged , Carcinoma, Squamous Cell/pathology , Cell Differentiation , Esophageal Neoplasms/pathology , Female , Humans , Immunohistochemistry , Lymphatic Metastasis , Male , Middle Aged , Multivariate Analysis , Neoplasm Invasiveness , Prognosis , Proportional Hazards Models
16.
Dig Dis Sci ; 55(9): 2545-51, 2010 Sep.
Article in English | MEDLINE | ID: mdl-19960259

ABSTRACT

BACKGROUND: So far, the miRNAs involved in multidrug resistance of esophageal cancer have not been reported. AIMS AND METHODS: Here we have firstly investigated the roles of miR-27a in multidrug resistance of esophageal squamous cell carcinoma using MTT assay, flow cytometry assay, and reporter gene assay, etc. RESULTS: Down-regulation of miR-27a could confer sensitivity of both P-glycoprotein-related and P-glycoprotein-non-related drugs on esophageal cancer cells, and might promote ADR-induced apoptosis, accompanied by increased accumulation and decreased releasing amount of ADR. Down-regulation of miR-27a could significantly decrease the expression of P-glycoprotein, Bcl-2, and the transcription of the multidrug resistance gene 1, but up-regulate the expression of Bax. CONCLUSIONS: MiR-27a might play important roles in multidrug resistance of esophageal cancer. The further study of the biological functions of miR-27a might be helpful for developing possible strategies to treat esophageal cancer.


Subject(s)
Apoptosis/genetics , Carcinoma, Squamous Cell/genetics , Drug Resistance, Multiple/genetics , Drug Resistance, Neoplasm/genetics , Esophageal Neoplasms/genetics , MicroRNAs/metabolism , ATP Binding Cassette Transporter, Subfamily B , ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , Antineoplastic Agents/metabolism , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/pathology , Cell Line, Tumor , Cell Survival/drug effects , Cisplatin/pharmacology , Dose-Response Relationship, Drug , Down-Regulation , Doxorubicin/metabolism , Doxorubicin/pharmacology , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/pathology , Fluorouracil/pharmacology , Humans , Inhibitory Concentration 50 , Proto-Oncogene Proteins c-bcl-2/metabolism , Transfection , Vincristine/pharmacology , bcl-2 Homologous Antagonist-Killer Protein/metabolism , bcl-2-Associated X Protein/metabolism , bcl-X Protein/metabolism
17.
Hybridoma (Larchmt) ; 28(2): 129-32, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19249995

ABSTRACT

We have efficiently generated the first monoclonal antibody against the cis-aconitic acid decarboxylase (CAD) protein, which is an enzyme of low stability. Hybridomas were screened by indirect enzyme-linked immunosorbent assay (ELISA) using either purified 6 x His-CAD fusion protein or purified 6 x His-ZNRD1 fusion protein as a control. One monoclonal antibody (MAb) named Z12 (IgG1), which is effective in detecting the recombinant and the cellular protein, was characterized by ELISA and Western immunoblotting. The CAD protein was also detected in gastric cancer and colon cancer tissues by immunohistochemical analysis. Thus, Z12 binds to native CAD protein and should be useful in studies of CAD protein function and expression.


Subject(s)
Antibodies, Monoclonal/biosynthesis , Aspartate Carbamoyltransferase/immunology , Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing)/immunology , Dihydroorotase/immunology , Hybridomas/immunology , Blotting, Western , Cell Line, Tumor , Enzyme-Linked Immunosorbent Assay , Humans , Immunoglobulin G/immunology , Immunohistochemistry
18.
Ann Surg Oncol ; 14(9): 2621-7, 2007 Sep.
Article in English | MEDLINE | ID: mdl-17570016

ABSTRACT

PURPOSE: MG7-Ag is a human gastric-carcinoma-associated antigen. The expression of MG7-Ag was found to increase gradually with the development and progression of gastric cancer. Moreover, a poorer prognosis was found in MG7-Ag positive gastric-carcinoma patients than in MG7-Ag negative patients. However, neither MG7-Ag expression nor its clinical significance has been previously examined in squamous cell carcinoma (SCC) of the esophagus. In this study, we examined the expression of MG7-Ag in esophageal squamous cell carcinomas to assess its value as a prognostic indicator. METHODS: The expression of MG7-Ag was detected in 112 cases of esophageal squamous cell carcinoma (SCC) by immunohistochemical analysis. The relation of MG7-Ag staining with various clinicopathological features was statistically analyzed. RESULTS: The staining of MG7-Ag was detected in SCC, while not in normal epithelial cells. In esophageal SCC, MG7-Ag was found significantly correlated with depth of invasion (P = .012), in T4, T3 carcinomas but not in T2, T1 carcinomas, lymph node metastases (P = .029), pathological stage (P = .005). Consistently, the survival rate tended to be statistically lower in patients with MG7-Ag positive SCCs than in MG7-Ag negative SCCs (P = .005). However, no significant difference was observed between MG7-expression and patient age, sex, tumor location, differentiation, distant metastasis, and lymphatic invasion. CONCLUSION: MG7-Ag might play a positive role in the process of carcinogenesis and progression of esophageal SCC, and it could be considered as one valuable prognostic indicator in esophageal SCC.


Subject(s)
Antigens, Neoplasm/analysis , Carcinoma, Squamous Cell/immunology , Carcinoma, Squamous Cell/surgery , Esophageal Neoplasms/immunology , Esophageal Neoplasms/surgery , Biomarkers, Tumor/analysis , Carcinoma, Squamous Cell/pathology , Chi-Square Distribution , Disease Progression , Esophageal Neoplasms/pathology , Esophagectomy , Female , Humans , Immunohistochemistry , Male , Middle Aged , Prognosis , Proportional Hazards Models , Statistics, Nonparametric , Survival Analysis
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