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1.
Math Biosci Eng ; 16(4): 2942-2958, 2019 04 10.
Article in English | MEDLINE | ID: mdl-31137244

ABSTRACT

Colorectal cancer (CRC) is one of the most common malignancies, giving rise to serious financial burden globally. This study was designed to explore the potential mechanisms implicated with CRC and identify some key biomarkers. CRC-associated gene expression dataset (GSE32323) was downloaded from GEO database. The differentially expressed genes (DEGs) were selected out based on the GEO2R tool. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were employed to search the enriched pathways of these DEGs. Additionally, a protein-protein interaction (PPI) network was also constructed to visualize interactions between these DEGs. Quantitative Real-time PCR (qPCR) was further performed to valid the top5 up-regulated and top5 down-regulated genes in patients with CRC. Finally, the survival analysis of the top5 up-regulated and top5 down-regulated genes was conducted using GEPIA, aiming to clarify their potential effects on CRC. In this study, a total of 451 DEGs were captured (306 down-regulated genes and 145 up-regulated genes). Among these DEGs, the top5 up-regulated genes were DPEP1, KRT23, CLDN1, LGR5 and FOXQ1 while the top5 down-regulated genes were CLCA4, ZG16, SLC4A4, ADH1B and GCG. GO analysis revealed that these DEGs were mainly enriched in cell adhesion, cell proliferation, RNA polymerase II promoter and chemokine activity. KEGG analysis disclosed that the enriched pathway included mineral absorption, chemokine signaling pathway, transcriptional misregulation in cancer, pathways in cancer and PPAR signaling pathway. Survival analysis showed that the expression level of ZG16 may correlate with the prognosis of CRC patients. Furthermore, according to the connectivity degree of these DEGs, we selected out the top15 hub genes, namely MYC, CXCR1, TOP2A, CXCL12, SST, TIMP1, SPP1, PPBP, CDK1, THBS1, CXCL1, PYY, LPAR1, BMP2 and MMP3, which were expected to be promising therapeutic target in CRC. Collectively, our analysis unveiled potential biomarkers and candidate targets in CRC, which could be helpful to the diagnosis and treatment of CRC.


Subject(s)
Colorectal Neoplasms/genetics , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Chemokines/genetics , Chemokines/metabolism , Colorectal Neoplasms/metabolism , Computational Biology , Databases, Genetic , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Gene Ontology , Humans , Mathematical Concepts , Prognosis , Protein Interaction Maps/genetics , Signal Transduction/genetics
2.
Sci Rep ; 7(1): 3689, 2017 06 16.
Article in English | MEDLINE | ID: mdl-28623296

ABSTRACT

This study evaluated if iodine-125 brachytherapy prophylaxis after radiofrequency ablation (RFA) prolongs time to recurrence (TTR) and overall survival (OS) of patients in high risk of locoregional hepatocellular carcinoma (HCC) recurrence. 116 patients with total tumor necrosis after RFA were divided into iodine-125 brachytherapy prophylaxis treatment group and control group. The primary endpoint was TTR, and secondary endpoints were OS and treatment-related adverse events. There were no significant differences among the baseline characteristics of two subgroups patients. The mean iodine-125 particles were 29.8 (26.59 ± 12.51 mCi) per patient. The mean follow-up was 25 months, and mean TTR of treatment and control groups were 21.7 and 15.9 months (P = 0.733); mean OS of two subgroups were 41.7 and 40.9 months (P = 0.316). There were no significant differences of 1-, 2-, 3-, 4-and 5-years TTR and OS and patients' immunity pre- and 1 month post-treatment. Extrahepatic metastasis was found to have a statistically significant influence on TTR, and AFP, extrahepatic metastasis were found to have a statistically significant influence on OS by multivariate analysis. There was no major complications and procedure related death. Iodine-125 brachytherapy prophylaxis after RFA can't improve TTR and OS of HCC patients who were in high risk of locoregional tumor recurrence.


Subject(s)
Brachytherapy , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/therapy , Iodine Radioisotopes/therapeutic use , Liver Neoplasms/pathology , Liver Neoplasms/therapy , Adolescent , Adult , Aged , Aged, 80 and over , Biomarkers , Brachytherapy/methods , Carcinoma, Hepatocellular/mortality , Combined Modality Therapy , Humans , Liver Neoplasms/mortality , Middle Aged , Neoplasm Metastasis , Neoplasm Staging , Proportional Hazards Models , Radiofrequency Ablation/methods , Retrospective Studies , Treatment Outcome , Young Adult
3.
Tumour Biol ; 39(5): 1010428317701656, 2017 May.
Article in English | MEDLINE | ID: mdl-28475013

ABSTRACT

Our study aims to evaluate the efficacy of transcatheter arterial chemoembolization in the treatment of patients with liver metastasis using integrated 18F-fluorodeoxyglucose positron emission tomography/computed tomography. A total of 97 liver metastasis patients treated by transcatheter arterial chemoembolization were enrolled in this study. The 18F-fluorodeoxyglucose positron emission tomography/computed tomography images of liver metastasis patients were collected before and after transcatheter arterial chemoembolization treatment. The efficacy of transcatheter arterial chemoembolization for the treatment of liver metastasis was evaluated according to the revised Response Evaluation Criteria in Solid Tumors guidelines. The receiver operating characteristic curve analysis was used to determine cut-off values of 18F-fluorodeoxyglucose positron emission tomography parameters (Tsuvmax, Tsuvmax/Lsuvmax, and Tsuvmax/Lsuvmean) for predicting the efficacy of transcatheter arterial chemoembolization. Progression-free survival and the incidence of postoperative complications were compared. Correlation of Tsuvmax, Tsuvmax/Lsuvmax, and Tsuvmax/Lsuvmean with blood supply and lipiodol deposition in the lesion was analyzed. Among three 18F-fluorodeoxyglucose positron emission tomography parameters, the receiver operating characteristic analysis showed that Tsuvmax/Lsuvmax with a cut-off value of 3.56 was the best predictor of transcatheter arterial chemoembolization efficacy. According to the cut-off value of Tsuvmax/Lsuvmax, liver metastasis patients were divided into the Tsuvmax/Lsuvmax ≤ 3.56 and Tsuvmax/Lsuvmax > 3.56 groups. Compared with the Tsuvmax/Lsuvmax > 3.56 group, the Tsuvmax/Lsuvmax ≤ 3.56 group showed a longer progression-free survival and a lower incidence of postoperative complications. The Tsuvmax, Tsuvmax/Lsuvmax, and Tsuvmax/Lsuvmean in the lesion with abundant blood supply were significantly lower than those in peripheral liver parenchyma, while the Tsuvmax, Tsuvmax/Lsuvmax, and Tsuvmax/Lsuvmean in the lesion with lack of blood supply were significantly higher than those in peripheral liver parenchyma. Spearman correlation analysis indicated that lipiodol deposition in the lesion was positively correlated with the Tsuvmax, Tsuvmax/Lsuvmax, and Tsuvmax/Lsuvmean. The Tsuvmax/Lsuvmax of 18F-fluorodeoxyglucose positron emission tomography/computed tomography may be a good tool for predicting the blood supply and efficacy of transcatheter arterial chemoembolization for patients with liver metastasis.


Subject(s)
Carcinoma, Hepatocellular/diagnostic imaging , Chemoembolization, Therapeutic , Liver Neoplasms/diagnostic imaging , Positron Emission Tomography Computed Tomography , Adult , Aged , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/secondary , Disease-Free Survival , Ethiodized Oil/administration & dosage , Female , Fluorodeoxyglucose F18/therapeutic use , Humans , Liver/blood supply , Liver/diagnostic imaging , Liver/pathology , Liver Neoplasms/pathology , Liver Neoplasms/secondary , Male , Middle Aged , Postoperative Complications/diagnostic imaging , Postoperative Complications/pathology , Radiopharmaceuticals/therapeutic use
4.
J Cell Mol Med ; 21(9): 1989-1999, 2017 09.
Article in English | MEDLINE | ID: mdl-28429395

ABSTRACT

To investigate the effects of lentiviral vector-mediated shRNA suppressing CXCR7 on tumour invasion and metastasis in hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE). HCCLM3 cell lines were cultured and assigned into the CXCR7-shRNA, negative control (NC) and blank groups. The qRT-PCR and Western blotting were applied to detect the mRNA and protein expressions of CXCR7, CXCR4 and MMP-2 in HCCLM3 cells. Cell proliferation and invasion were evaluated by MTT and Transwell assays. A Buffalo rat model of HCC was established. Fifty model rats were divided into the CXCR7-shRNA + TACE, CXCR7-shRNA, TACE, NC and control groups. Immunohistochemistry was performed to detect the expressions of CXCR7, MMP-2, vascular endothelial growth factor (VEGF) and intratumoral CD31-positive vessel count in tumour tissues of mice. Compared with the blank and NC groups, the mRNA and protein expressions of CXCR7 and MMP-2 were decreased in the CXCR7-shRNA group. The cell proliferation and invasion rates of the CXCR7-shRNA group were lower than the blank and NC groups. At the 4th week after TACE, tumour weight of the CXCR7-shRNA + TACE group increased continuously. The CXCR7-shRNA + TACE group showed longer survival time and smaller tumour sizes than other groups. Compared with other groups, the CXCR7-shRNA + TACE and CXCR7-shRNA groups had less number of lung metastatic nodules and lower expressions of CXCR7, MMP-2, VEGF and CD31-positive vessel count. CXCR7-shRNA inhibits tumour invasion and metastasis to improve the efficacy of TACE in HCC by reducing the expressions of CXCR7, MMP-2 and VEGF.


Subject(s)
Carcinoma, Hepatocellular/therapy , Chemoembolization, Therapeutic , Gene Knockdown Techniques , Hepatic Artery/pathology , Liver Neoplasms/therapy , RNA, Small Interfering/metabolism , Receptors, CXCR/metabolism , Animals , Carcinoma, Hepatocellular/pathology , Cell Line, Tumor , Humans , Liver Neoplasms/pathology , Male , Neoplasm Invasiveness , Neoplasm Metastasis , Rats
5.
Sci Rep ; 6: 35056, 2016 10 11.
Article in English | MEDLINE | ID: mdl-27725696

ABSTRACT

Hepatocellular carcinoma (HCC) is a common malignant tumour, especially in Asia. Its prognosis is poor, and there are limited methods for predicting patient survival. This study was carried out to analyse the prognostic value of tumour-infiltrating lymphocytes (TILs), especially regulatory T cells (Tregs), in HCC patients. TILs were analysed in 57 randomly selected HCC patients. The prognostic effects of groups with high and low numbers were evaluated by the Kaplan-Meier and Cox model analyses. Although higher densities of CD3+, CD4+, and CD8+ cytotoxic lymphocytes (CTLs) as well as CD56+ NK cells and CD68+ macrophages were observed in peritumoural tissue, increased numbers of forkhead/winged helix transcription factor P3+ (FOXP3+) Tregs were found in intratumoural tissue. Additionally, regarding ICOS+ FOXP3+ Tregs, an increased prevalence in carcinoma was not only associated with the absolute number but also with the percentage of FOXP3+ cells. Higher Treg levels in tumour tissues indicated a worse prognosis, and the FOXP3+ Tregs/CD4+ T cells ratio was an independent prognostic factor for OS. Therefore, FOXP3+ Tregs, especially ICOS+ FOXP3+ Tregs, contribute to the immunosuppressive HCC microenvironment. High tumour-infiltrating Tregs are thought to be an unfavourable prognostic indicator of HCC.


Subject(s)
Carcinoma, Hepatocellular/pathology , Forkhead Transcription Factors/metabolism , Inducible T-Cell Co-Stimulator Protein/metabolism , Liver Neoplasms/pathology , T-Lymphocytes, Regulatory/immunology , Adult , CD4-Positive T-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/metabolism , Carcinoma, Hepatocellular/immunology , Female , Humans , Liver Neoplasms/immunology , Lymphocytes, Tumor-Infiltrating , Male , Middle Aged , Prognosis , Random Allocation , Survival Analysis , Tumor Microenvironment
6.
Zhonghua Liu Xing Bing Xue Za Zhi ; 34(5): 520-2, 2013 May.
Article in Chinese | MEDLINE | ID: mdl-24016447

ABSTRACT

OBJECTIVE: To explore the correlation between mental disorder and craniocerebral injury, and notifying its related risk factors. METHODS: 342 patients from Sep. 2008 to Sep. 2012 with craniocerebral injury were selected and related clinical data on general their conditions, including sex, age, educational level, satisfaction on careers and relations to family were collected. All the patients received CT-scans to the head, IQ test, MQ test, SCID-1/P, PDQC and SCICP detection. Multivariate logistic regression was used to analyze the general information and cerebral injurious conditions of patients regarding the incidence of mental disorders. RESULTS: 249 patients with mental disorder were noticed out of the total 342 patients with craniocerebral injury, with the incidence rate as 72.8% including 117 depression (47.0%), 95 anxiety disorders (38.2%), 27 mania (10.8%), 69 intelligence and memory disorders (27.7%) cases. Data from correlation analysis showed that factors as sex, age, educational level, satisfaction on careers and family of patients as well as type, severity and location of the craniocerebral injuries appeared to have important correlation with mental disorder. RESULTS: also showed that the age of patients (OR > 1.04), severity and location of the craniocerebral injuries (OR1 > 1.28, OR2 > 1.31) were independent risk factors (P < 0.05). CONCLUSION: The age of patients, severity and location of the craniocerebral injuries were independent risk factors for mental disorder in patients with craniocerebral injury.


Subject(s)
Craniocerebral Trauma/complications , Craniocerebral Trauma/psychology , Mental Disorders/etiology , Adult , Aged , Female , Humans , Incidence , Logistic Models , Male , Middle Aged , Risk Factors
7.
Fa Yi Xue Za Zhi ; 29(6): 437-9, 2013 Dec.
Article in Chinese | MEDLINE | ID: mdl-24665615

ABSTRACT

OBJECTIVE: To study the disability identification for cases with clinical diagnosis of diffuse axonal injury (DAI) due to traffic accidents, and to explore the possible effects of DAI on identification results. METHODS: Five hundred and fifty-six cases of cerebral injury due to traffic accidents were collected, including 467 cases diagnosed with cerebral contusion or laceration and 89 cases diagnosed with DAI. The identification results of different groups with diagnosis of DAI diagnosis, diagnosis of DAI with cerebral contusion (laceration), and diagnosis of cerebral contusion or laceration without DAI were compared and statistically analyzed, based on the results of CT and MRI re-review. RESULTS: The disability identification levels in DAI group (20 cases), DAI group (69 cases) with cerebral contusion (laceration) and DAI group (467 cases) not complicated by cerebral contusion (laceration) were 7.72 +/- 1.09, 7.78 +/- 1.11, and 8.86 +/- 0.66, respectively. The disability levels of the two groups diagnosed with DAI were higher than those of the group without DAI diagnosis (P < 0.05). CONCLUSION: Patients with DAI diagnosis might have more severe cerebral injury. In the identification process, one should pay attention to the possible missed diagnosis and misdiagnosis, and meanwhile avoid relying on those evidences provided only by CT and MRI.


Subject(s)
Accidents, Traffic , Brain Injuries/complications , Diffuse Axonal Injury/diagnosis , Disability Evaluation , Forensic Pathology , Brain Injuries/diagnosis , Diagnostic Errors , Diffuse Axonal Injury/etiology , Humans , Magnetic Resonance Imaging , Resin Cements , Tomography, X-Ray Computed
8.
Fa Yi Xue Za Zhi ; 25(6): 428-30, 2009 Dec.
Article in Chinese | MEDLINE | ID: mdl-20225618

ABSTRACT

OBJECTIVE: To analyze the relevant factors of determining the degree of mental disability after brain injuries in the traffic accidents. METHODS: A total of 157 forensic psychiatry cases involving the assessment of mental disability caused by traffic accidents were collected and divided into three groups (mild, moderate and severe) according to the conclusion of the forensic identification. The demographic, clinical and forensic data were compared in the three groups and analyzed with ordinal logistic regression. RESULTS: There was no statistically significant difference in the demographic data among three groups (P > 0.05). While there was statistically significant difference in the coma duration, severity of intracranial hemorrhage, working capacity, family duties, social functions, self care capacity and intelligence quotient (P < 0.05) among the groups. Intracranial hemorrhage, family duties, social functions and self care capacity were chosen as the factors in the logistic regression equation. CONCLUSION: The degree of the brain damage influenced the mental disability. Family duties, social functions and self care capacity are the major factors for determining the degree of mental disability after injured.


Subject(s)
Accidents, Traffic , Brain Injuries/pathology , Disability Evaluation , Mental Disorders/diagnosis , Adult , Brain Injuries/complications , Female , Forensic Psychiatry , Humans , Injury Severity Score , Male , Mental Disorders/etiology , Middle Aged , Work Capacity Evaluation
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