PTX3 promotes breast cancer cell proliferation and metastasis by regulating PKCζbreast cancer, pentraxin 3, protein kinase Cζ, proliferation, metastasis.

Breast cancer (BC) is the most commonly diagnosed cancer in women, providing a leading cause of death from malignancy. Pentraxin 3 (PTX3) and protein kinase C ζ (PKCζ) are both known to exert important roles in the progression of multiple types of tumors, including BC. The present study aimed to explore both their interaction and their role in promoting the proliferation and metastasis of BC. The expression level of PTX3 was found to be elevated both in patients with BC and in BC cells; furthermore, it was found to be associated with lymph node metastasis in patients with BC. Knockdown of PTX3 decreased the rate of cell proliferation and the effects of a series of metastasis-associated cellular processes, including cell chemotaxis, migration, adhesion and invasion, as well as diminishing actin polymerization of the MDA-MB-231 and MCF7 BC cells, and decreasing tumor pulmonary metastasis in vivo. Mechanistically, PTX3 and PKCζ were found to be colocalized intracellularly, and they were co-translocated to the cell membrane upon stimulation with epidermal growth factor. Following the knockdown of PTX3, both the phosphorylation and membrane translocation of PKCζ were significantly impaired, suggesting that PTX3 regulates the activation of PKCζ. Taken together, the findings of the present study have shown that PTX3 may promote the proliferation and metastasis of BC cells through regulating PKCζ activation to enhance cell migration, cell chemotaxis, cell invasion and cell adhesion.

Establishment and Validation of a Blood Test-based Nomogram to Diagnose Patients with AFP-negative HCC.

BACKGROUND: Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer death worldwide. Alpha-protein (AFP) is the most widely used blood biomarker for HCC. However, elevated serum AFP is only observed in part of HCC. AIMS: This study aimed to develop an efficient nomogram model to distinguish patients with alpha- protein-negative HCC and liver cirrhosis. OBJECTIVE: A total of 1130 patients (508 HCC patients + 622 cirrhosis patients) were enrolled in the training cohort. A total of 244 HCC patients and 246 cirrhosis patients were enrolled in the validation cohort. METHOD: A total of 41 parameters about blood tests were analyzed with logistic regression. The nomogram was based on independent factors and validated both internally and externally. RESULTS: Independent factors were eosinophils %, hemoglobin concentration distribution width, fibrinogen, platelet counts, total bile acid, and mitochondria aspartate aminotransferase. The calibration curve for the probability of HCC showed good agreement between prediction by nomogram and actual observation. The concordance index was 0.851. In the validation cohort, the nomogram distinguished HCC from liver cirrhosis with an area under the curve of receiver operating characteristic of 0.754. CONCLUSION: This proposed nomogram was an accurate and useful method to distinguish patients with AFP-negative HCC from liver cirrhosis.

Brachybacterium muris Detected in a Hepatocellular Carcinoma Patient with Pleural Effusion: A Case Report.

Background: Brachybacterium muris is a species of Gram positive and strictly aerobic bacterium. It was first reported in 2003 after being isolated from the liver of a laboratory mouse strain. It was also found on human skin and nasal cavity. Herein, we present the first case pleural effusion infection in humans caused by Brachybacterium muris. Case Presentation: A 65-year-old man was admitted to our hospital for a 4-week history of fever, accompanied by chills, occasional abdominal pain, occasional chest tightness and shortness of breath. On the day of hospitalization, thoracentesis was performed and 1000mL of yellow cloudy fluid was released. Result of pleural fluid culture was positive and B. muris was identified using 16S rDNA amplification and sequence comparisons. Conclusion: To our knowledge, this is the first report of pleural effusion infection caused by B. muris. B. muris can be pathogenic in humans.

Identifying Mitochondrial Transcription Factor A As a Potential Biomarker for the Carcinogenesis and Prognosis of Prostate Cancer.

Aims: Mitochondrial functional transformation contributes to the carcinogenesis of the prostate by meeting the metabolic needs of cancer cells. Mitochondrial transcription factor A (TFAM) is a pivotal regulator that maintains homeostasis of mitochondrial function. However, its role in prostate carcinogenesis has not been well elucidated. Materials and Methods: In the present study, we analyzed the expression of TFAM in normal prostate tissue and prostate cancer using public databases; a prostate-tissue chip was used to verify the results. The expression of TFAM in normal cells and in prostate cancer cells was determined by western blotting analysis. We knocked down TFAM in the prostate cancer cell line PC3 using a specific shRNA to explore the potential effects of TFAM in prostatic carcinogenesis. Results: We observed higher expression levels of TFAM in prostate cancer tissue than in normal prostate tissue and tumor adjacent normal tissues. A receiver operating characteristic curve was drawn that demonstrated the diagnostic efficacy of using TFAM expression for prostate cancer prognoses. Elevated levels of TFAM may indicate poorer overall survival in prostate cancer patients. Western blotting assays also showed that relative to the normal prostatic epithelial cell line RWPE-1, prostate cancer cell lines PC3 and DU145 expressed more TFAM protein. Furthermore, knockdown of TFAM inhibited the colony-formation capability of PC3 cells. Conclusion: Collectively, these results suggest that TFAM promotes carcinogenesis of the prostate, and may constitute a marker to be used in the diagnosis and prognosis of prostate cancer.

Diagnostic and prognostic nomograms for newly diagnosed intrahepatic cholangiocarcinoma with brain metastasis: A population-based analysis.

Brain metastasis (BM) is one of the rare metastatic sites of intrahepatic cholangiocarcinoma (ICC). ICC with BM can seriously affect the quality of life of patients and lead to a poor prognosis. The aim of this study was to establish two nomograms to estimate the risk of BM in ICC patients and the prognosis of ICC patients with BM. Data on 19,166 individuals diagnosed with ICC were retrospectively collected from the Surveillance, Epidemiology, and End Results (SEER) database. Independent risk factors and prognostic factors were identified by the logistic and the Cox regression, respectively. Next, two nomograms were developed, and their discrimination was estimated by concordance index (C-index) and calibration plots, while the clinical benefits of the prognostic nomogram were evaluated using the receiver operating characteristic (ROC) curves, the decision curve analysis (DCA), and the Kaplan-Meier analyses. The independent risk factors for BM were T stage, N stage, surgery, alpha-fetoprotein (AFP) level, and tumor size. T stage, surgery, radiotherapy, and bone metastasis were prognostic factors for overall survival (OS). For the prognostic nomogram, the C-index was 0.759 (95% confidence interval (CI) = 0.745-0.773) and 0.764 (95% CI = 0.747-0.781) in the training and the validation cohort, respectively. The calibration curves revealed a robust agreement between predictions and actual observations probability. The area under curves (AUCs) for the 3-, 6-, and 9-month OS were 0.721, 0.727, and 0.790 in the training cohort and 0.702, 0.777, and 0.853 in the validation cohort, respectively. The DCA curves yielded remarkable positive net benefits over a wide range of threshold probabilities. The Kaplan-Meier analysis illustrated that the nomogram could significantly distinguish the population with different survival risks. We successfully established the two nomograms for predicting the incidence of BM and the prognosis of ICC patients with BM, which may assist clinicians in choosing more effective treatment strategies.

Metabolomics Identifies Biomarker Signatures to Differentiate Pancreatic Cancer from Type 2 Diabetes Mellitus in Early Diagnosis.

METHODS: Plasma metabolic profiles in 26 PC patients, 27 DM patients, and 23 healthy volunteers were examined using an ultraperformance liquid chromatography coupled with tandem mass spectrometry platform. Differential metabolite ions were then identified using the principal component analysis (PCA) model and the orthogonal partial least-squares discrimination analysis (OPLS-DA) model. The diagnosis performance of metabolite biomarkers was validated by logistic regression models. RESULTS: We established a PCA model (R2X = 23.5%, Q2 = 8.21%) and an OPLS-DA model (R2X = 70.0%, R2Y = 84.9%, Q2 = 69.7%). LysoPC (16 : 0), catelaidic acid, cerebronic acid, nonadecanetriol, and asparaginyl-histidine were found to identify PC, with a sensitivity of 89% and a specificity of 91%. Besides, lysoPC (16 : 0), lysoPC (16 : 1), lysoPC (22 : 6), and lysoPC (20 : 3) were found to differentiate PC from DM, with higher accuracy (68% versus 55%) and higher AUC values (72% versus 63%) than those of CA19-9. The diagnostic performance of metabolite biomarkers was finally validated by logistic regression models. CONCLUSION: We succeeded in screening differential metabolite ions among PC and DM patients and healthy individuals, thus providing a preliminary basis for screening the biomarkers for the early diagnosis of PC.

Identification and Validation of Hub Genes Associated With Hepatocellular Carcinoma Via Integrated Bioinformatics Analysis.

Hepatocellular carcinoma (HCC) is the most common malignant tumor of the liver, with high morbidity and mortality, yet its molecular mechanisms of tumorigenesis are still unclear. In this study, gene expression profile of GSE62232 was downloaded from the Gene Expression Omnibus (GEO). The RNA-seq expression data and relative clinical information were retrieved from the Cancer Genome Atlas (TCGA) database. The datasets were analyzed by differential gene expression analysis and Weighted Gene Co-expression Network Analysis (WGCNA) to obtain the overlapping genes. Then, we performed a functional enrichment analysis to understand the potential biological functions of these co-expression genes. Finally, we constructed the protein-protein interaction (PPI) analysis combined with survival analysis. MARCO, CLEC4M, FCGR2B, LYVE1, TIMD4, STAB2, CFP, CLEC4G, CLEC1B, FCN2, FCN3 and FOXO1 were identified as the candidate hub genes using the CytoHubba plugin of Cytoscape. Based on survival analysis, the lower expression of FCN3 and FOXO1 were associated with worse overall survival (OS) in HCC patients. Furthermore, the expression levels of FCN3 and FOXO1 were validated by the Human Protein Atlas (HPA) database and the qRT-PCR. In summary, our findings contribute new ideas for the precise early diagnosis, clinical treatment and prognosis of HCC in the future.

Prognostic Nomograms to Predict Overall Survival and Cancer-Specific Survival of Patients With Pancreatic Neuroendocrine Tumors: A Population-Based Study.

OBJECTIVE: The objective of this research was to construct and validate prognostic nomograms predicting overall survival (OS) and cancer-specific survival (CSS) in patients with pancreatic neuroendocrine tumors (pNETs). METHODS: We extracted 3787 patients with pNETs from the Surveillance, Epidemiology and End Results database. Nomograms for estimating 3- and 5-year OS and CSS were first established. Then, we used Harrell's Concordance Index, calibration plots, and the area under receiver operating characteristic curve to evaluate the nomograms. The Kaplan-Meier curve was plotted to evaluate the different survival outcomes. RESULTS: In the multivariate analysis, age, grade, functional status, American Joint Committee on Cancer stage, and surgery were associated with OS and CSS. The established nomograms had good discriminative ability, with a Harrell's Concordance Index of 0.830 for OS and 0.855 for CSS. The calibration plots also revealed good agreement. The area under receiver operating characteristic curve values of the nomograms predicting 3- and 5-year OS and CSS rates were 0.836, 0.816 and 0.859, 0.841, respectively. In addition, Kaplan-Meier curve indicated that patients with higher risk had worse survival outcomes. CONCLUSIONS: We have proposed and validated the nomograms predicting OS and CSS of pNETs. They can be convenient individualized tools to facilitate clinical decision making.

The prognostic analysis of different metastatic patterns in pancreatic neuroendocrine tumors patients: A population based analysis.

OBJECTIVE: To evaluate the prognostic value of pancreatic neuroendocrine tumors (pNETs) with different metastatic patterns. METHODS: Data of pNETs cases were extracted from the Surveillance, Epidemiology, and End Result (SEER) database. They were classified according to the different metastatic patterns. We utilized chi-square test to compare the clinical and metastasis characteristics among different groups. We used Kaplan-Meier analysis and log-rank testing for survival comparisons. Adjusted HRs with 95% CIs was calculated using Cox regression model to estimate prognostic factors. P < .05 was considered statistically significant. RESULTS: Among the 3909 patients, liver is the most metastatic organ, and isolated brain metastasis is the least common. At the same time, many patients have had multiple metastases. We studied the overall survival (OS) and cancer-specific survival (CCS) of the groups. OS: Non-organ metastasis: 5-year OS = 77.1%; Bone metastasis: median survival time (MST) = 56 m, 5-year OS = 42.7%; Liver metastasis: MST = 24 m, 5-year OS = 25.5%; Lung metastasis: MST = 14 m, 5-year OS = 33.7%; multiple metastases: MST = 7m, 5-year OS = 12.0%. CCS: Non-organ metastasis: 5-year OS = 84.2%; Bone metastasis: 5-year OS = 52.5%; Liver metastasis: MST = 27 m, 5-year OS = 28.6%; Lung metastasis: MST = 49 m, 5-year OS = 40.1%; multiple metastases: MST = 8 m, 5-year OS = 14.5%. In addition, the results showed that there were all statistical significances between the surgery and the no surgery group (all, P < .001). Multivariate analysis revealed that brain metastasis, multiple metastases, age over 60 years, unmarried, grade III/IV, regional/distant and no surgery were independently associated with decreased OS and CCS. CONCLUSIONS: pNETs patients without organ metastasis had the best survival outcomes, while multiple had the worst outcomes. There were no significant differences in bone metastasis, liver metastasis and lung metastasis. Surgery was still an option for patients with metastasis.

[High-performance liquid chromatography-mass spectrometry-based serum metabolic profiling in patients with HBV-related hepatocellular carcinoma].

OBJECTIVE: To explore the diagnostic value of the serum metabolites identified by high-performance liquid chromatography-mass spectrometry (HPLC/MS) for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). METHODS: A total of 126 patients admitted to Tianjin Third Central Hospital were enrolled, including 27 patients with HBV-related hepatitis with negative viral DNA (DNA-N), 24 with HBV-related hepatitis with positive viral DNA, 24 with HBV-related liver cirrhosis, 27 with HBV-related HCC undergoing surgeries or radiofrequency ablation, and 24 with HBV-related HCC receiving interventional therapy, with 25 healthy volunteers as the normal control group. Serum samples were collected from all the subjects for HPLC/MS analysis, and the data were pretreated to establish an orthogonal partial least- squares discriminant analysis (OPLS-DA) model. The differential serum metabolites were preliminarily screened by comparisons between the HBV groups and the control group, and the characteristic metabolites were identified according to the results of non-parametric test. The potential clinical values of these characteristic metabolites were evaluated using receiver operator characteristic curve (ROC) analysis. RESULTS: A total of 25 characteristic metabolites were identified in the HBV- infected patients, including 9 lysophosphatidylcholines, 2 fatty acids, 17α-estradiol, sphinganine, 5-methylcytidine, vitamin K2, lysophosphatidic acid, glycocholic acid and 8 metabolites with few reports. The patients with HBV- related HCC showed 22 differential serum metabolites compared with the control group, 4 differential metabolites compared with patients with HBV-related liver cirrhosis; 10 differential metabolites were identified in patients with HBV-related HCC receiving interventional therapy compared with those receiving surgical resection or radiofrequency ablation. From the normal control group to HBV-related HCC treated by interventional therapy, many metabolites underwent variations following a similar pattern. CONCLUSIONS: We identified 25 characteristic metabolites in patients with HBV-related HCC, and these metabolites may have potential clinical values in the diagnosis of HBV-related HCC. The continuous change of some of these metabolites may indicate the possibility of tumorigenesis, and some may also have indications for the choice of surgical approach.

Metabolomics research on potential role for 9-cis-retinoic acid in breast cancer progression.

Deciphering the molecular networks that discriminate organ-confined breast cancer from metastatic breast cancer may lead to the identification of critical biomarkers for breast cancer invasion and aggressiveness. Here metabolomics, a global study of metabolites, has been applied to explore the metabolic alterations that characterize breast cancer progression. We profiled a total of 693 metabolites across 87 serum samples related to breast cancer (46 clinically localized and 41 metastatic breast cancer) and 49 normal samples. These unbiased metabolomic profiles were able to distinguish normal individuals, clinically localized and metastatic breast cancer patients. 9-cis-Retinoic acid, an isomer of all-trans retinoic acid, was identified as a differential metabolite that significantly decreased during breast cancer progression to metastasis, and its levels were also reduced in urine samples from biopsy-positive breast cancer patients relative to biopsy-negative individuals and in invasive breast cancer cells relative to benign MCF-10A cells. The addition of exogenous 9-cis-retinoic acid to MDA-MB-231 cells and knockdown of aldehyde dehydrogenase 1 family member A1, a regulatory enzyme for 9-cis-retinoic acid, remarkably impaired cell invasion and migration, presumably through preventing the key regulator cofilin from activation and inhibiting MMP2 and MMP9 expression. Taken together, our study showed the potential inhibitory role for 9-cis-retinoic acid in breast cancer progression by attenuating cell invasion and migration.

The serum metabolic profiles of different Barcelona stages hepatocellular carcinoma associated with hepatitis B virus.

The present study aimed to explore the characteristic ions distinguishing different Barcelona stages in patients with hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) using the ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) platform, and to evaluate their value in diagnosing and monitoring the progress of HCC. The serum was sampled from 20 healthy volunteers, 20 patients with HBV-induced cirrhosis and 75 patients with HBV-associated HCC of different BCLC stages. Samples were all examined using UPLC-MS. Principal components analysis (PCA) and the orthogonal partial least squares discriminant analysis (OPLS-DA) model were constructed to determine potential biomarkers. Then, the independent sample-nonparametric test was used to perform the final screening for ion identification. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic value of these ions. Serum metabolomic PCA and OPLS-DA models were established to diagnose different BCLC stages of HCC associated with HBV, with OPLS-DA model parameters (R2X=67.2%, R2Y=82%, Q2Y=61.1%). A total of 20 metabolites with statistically significant differences among groups were identified, primarily including amino acids, bile acid, fatty acid and phosphatidate. The area under the curve (AUC) of LysoPC [18:2 (9Z,12Z)], LysoPC (P-16:0), asparaginyl-proline and vaccenic acid in the comparison between HCC and cirrhosis were all increased compared with that of AFP, indicating a more improved diagnosis ability. Furthermore, the AUC of L-aspartyl-4-phosphate and LysoPC [20:5 (5Z,8Z,11Z,14Z,17Z)] in the stage A vs. B comparison were increased compared with that of AFP, but were decreased in the comparison between stage B and C. The present study succeeded in screening metabolic ions that reflect the progress of HCC with high diagnostic value. Thus, the identified ions may serve a role in clinically diagnosing HBV-associated HCC and monitoring the development of the disease.

Metabolic profiling of hepatitis B virus-related hepatocellular carcinoma with diverse differentiation grades.

The most effective diagnostic tool for the majority of hepatocellular carcinoma (HCC) patients is determining the differentiation grade of their tumors. However liver biopsies, which are currently the most effective way of determining tumor differentiation grade, have several limitations. The present study was designed to select serum characteristic metabolites that correlate with the differentiation grades of hepatitis B virus (HBV)-related HCC, and so could be used in the clinic as a non-invasive method of differentiating patients with different grades of HCC. A total of 58 patients with HBV-related HCC were included in the present study, and divided into three groups according to their tumor differentiation grade. A further 20 patients with HBV-related liver cirrhosis and 19 healthy volunteers were enrolled. Ultra-performance liquid chromatography-mass spectrometry was used to analyze endogenous metabolites. Multivariate statistical analysis was used to examine the data using MZmine 2.0 software. The 14 metabolites that were highly correlated with specific differentiation grades of HCC were then selected for additional study. Receiver operator characteristic curve analysis was used to evaluate their clinical value. In total, 5 metabolites were finally identified, including lysophosphatidylcholine (16:0), oleamide, monoglyceride (0:0/15:0/0:0), lysophosphatidylcholine (18:0) and lysophosphatidylcholine [22:5(7Z,10Z,13Z,16Z,19Z)]. All these metabolites exhibited an excellent ability to distinguish different types of HCC with various differentiation grades and the area under the curve of these metabolites was up to 0.942, showing promising clinical value.

A novel and selective inhibitor of PKC ζ potently inhibits human breast cancer metastasis in vitro and in mice.

Cell motility and chemotaxis play pivotal roles in the process of tumor development and metastasis. Protein kinase C ζ (PKC ζ) mediates epidermal growth factor (EGF)-stimulated chemotactic signaling pathway through regulating cytoskeleton rearrangement and cell adhesion. The purpose of this study was to develop anti-PKC ζ therapeutics for breast cancer metastasis. In this study, a novel and high-efficient PKC ζ inhibitor named PKCZI195.17 was screened out through a substrate-specific strategy. MTT assay was used to determine the cell viability of human breast cancer MDA-MB-231, MDA-MB-435, and MCF-7 cells while under PKCZI195.17 treatment. Wound-healing, chemotaxis, and Matrigel invasion assays were performed to detect the effects of PKCZI195.17 on breast cancer cells migration and invasion. Adhesion, actin polymerization, and Western blotting were performed to detect the effects of PKCZI195.17 on cells adhesion and actin polymerization, and explore the downsteam signaling mechanisms involved in PKC ζ inhibition. MDA-MB-231 xenograft was used to measure the in vivo anti-metastasis efficacy of PKCZI195.17. The compound PKCZI195.17 selectively inhibited PKC ζ kinase activity since it failed to inhibit PKC α, PKC ß, PKC δ, PKC η, AKT2, as well as FGFR2 activity. PKCZI195.17 significantly impaired spontaneous migration, chemotaxis, and invasion of human breast cancer MDA-MB-231, MDA-MB-435, and MCF-7 cells, while PKCZI195.17 did not obviously inhibited cells viability. PKCZI195.17 also inhibited cells adhesion and actin polymerization through attenuating the phosphorylations of integrin ß1, LIMK, and cofilin, which might be the downstream effectors of PKC ζ-mediated chemotaxis in MDA-MB-231 cells. Furthermore, PKCZI195.17 suppressed the breast cancer metastasis and increased the survival time of breast tumor-bearing mice. In summary, PKCZI195.17 was a PKC ζ-specific inhibitor which dampened cancer cell migration and metastasis and may serve as a novel therapeutic drug for breast cancer metastasis.

Serum IgG4 and IgG for the diagnosis of autoimmune pancreatitis: A systematic review with meta-analysis.

BACKGROUND AND OBJECTIVE: The correct diagnosis of autoimmune pancreatitis (AIP) is a clinical challenge. Emerging published data on the accuracy of serum IgG4 and IgG for diagnosing AIP are inconsistent. This study was performed to better elucidate the accuracy of serum IgG4 and IgG in diagnosing AIP. METHODS: A comprehensive literature search of PubMed, Web of Science, EMBASE, the Cochrane Library and some other databases was conducted before October 2014. The methodological quality of each study was assessed according to the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) checklist. Random-effects model was used to summarize the sensitivity, specificity and other measures of accuracy. RESULTS: Fifteen studies on IgG4 and 8 studies on IgG were included. The summary estimates for serum IgG4 in distinguishing AIP from the overall controls, pancreatic cancer and ordinary chronic pancreatitis were as follows: sensitivity 0.74 (0.70-0.77), 0.73 (0.69-0.77) and 0.76 (0.72-0.80), respectively, specificity, 0.94 (0.93-0.95), 0.93 (0.91-0.95) and 0.96 (0.95-0.97), respectively. The summary estimates for serum IgG in distinguishing AIP from the overall controls and pancreatic cancer were as follows: sensitivity, 0.53 (0.47-0.59) and 0.51 (0.44-0.57), respectively, specificity, 0.87 (0.85-0.89) and 0.94 (0.91-0.96), respectively. The area under the curve (AUC) of serum IgG in distinguishing AIP from ordinary chronic pancreatitis was 0.657. CONCLUSIONS: Both serum IgG4 and IgG have high specificity and relatively low sensitivity for diagnosing AIP. Besides, they are useful for distinguishing AIP from pancreatic cancer and ordinary chronic pancreatitis. To better elucidate the usefulness of serum IgG4 and IgG, further studies are needed.

Cytotoxicity effect of graphene oxide on human MDA-MB-231 cells.

CONTEXT: The use of graphene oxide (GO) in biomedicine and cancer therapy has increased significantly owing to its unique physical and chemical properties. As a consequence, the toxicity of GO in the environment and in humans has garnered more and more attention. OBJECTIVE: In this paper, we studied the potential cytotoxicity of GO nanosheets via examining the effect of GO on the viability, cellular colony formation and proliferation of a human breast cancer MDA-MB-231 cell line, which was an ideal model used to study breast disease in vitro. METHODS AND RESULTS: The results suggested that higher concentrations of GO (≥100 µg/mL) exhibited time- and dose-dependent cytotoxicity against MDA-MB-231 cells, suppressed the colony-forming capacity and cellular proliferation. Moreover, higher concentrations of GO increased the proportion of G0/G1 phase cells and induced the LDH release, as well as the generation of intracellular ROS which was also remarkably increased and may directly related with cytotoxicity. CONCLUSION: Together, the above results suggested that GO can induce cytotoxicity against human breast cancer MDA-MB-231 cells probably due to the cellular ROS generation, which providing useful toxicity and mechanism information that can help to better inform safety assessments of GO.

Human liver tissue metabolic profiling research on hepatitis B virus-related hepatocellular carcinoma.

AIM: To select characteristic endogenous metabolites in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients and to identify their molecular mechanism and potential clinical value. METHODS: An ultra performance liquid chromatography and linear trap quadrupole-Orbitrap XL-mass spectrometry platform was used to analyze endogenous metabolites in the homogenate of central tumor tissue, adjacent tissue and distant tissue obtained from 10 HBV-related HCC patients. After pretreatment with Mzmine software, including peak detection, alignment and normalization, the acquired data were treated with Simca-P+software to establish multivariate statistical analysis based on a pattern recognition technique and characteristic metabolites highly correlated with changing trends in metabolic profiling were selected and further identified. RESULTS: Based on data acquired using Mzmine software, a principal component analysis model (R2X = 66.9%, Q2 = 21.7%) with 6 principal components and an orthogonal partial least squares discriminant analysis model (R2X = 76.5%, R2Y = 93.7%, Q2 = 68.7%) with 2 predicted principal components and 5 orthogonal principal components were established in the three tissue groups. Forty-nine ions were selected, 33 ions passed the 2 related samples nonparametric test (P < 0.05) and 14 of these were further identified as characteristic metabolites that showed significant differences in levels between the central tumor tissue group and distant tumor tissue group, including 9 metabolites (L-phenylalanine, glycerophosphocholine, lysophosphatidylcholines, lysophosphatidylethanolamines and chenodeoxycholic acid glycine conjugate) which had been reported as serum metabolite biomarkers for HCC diagnosis in previous research, and 5 metabolites (beta-sitosterol, quinaldic acid, arachidyl carnitine, tetradecanal, and oleamide) which had not been reported before. CONCLUSION: Characteristic metabolites and metabolic pathways highly related to HCC pathogenesis and progression are identified through metabolic profiling analysis of HCC tissue homogenates.

Positive ratio of specific antibodies to F protein in serum samples from chronic HCV-infected patients using an enzyme-linked immunosorbent assay: systematic review and meta-analysis.

AIMS AND BACKGROUND: Although some studies have reported a positive ratio of specific antibodies to the alternative reading frame protein in an enzyme-linked immunosorbent assay test, our data from meta-analysis provide evidence supporting the presence of circulating anti-F protein antibodies. METHODS: We collected studies focused on hepatitis C virus (HCV) and F protein. From an initial identification of 460 articles, we selected 16 studies that were randomized-controlled trials (RCTs). RESULTS: The results of the Mantel-Haenszel test showed that a statistically significant number of studies reported an effective value in chronic HCV-infected individuals (P<0.00001). We concluded that compared with healthy individuals, the positive ratio of F protein detection was higher in chronic HCV-infected individuals; the odds ratio was 63.61 [95% confidence interval (CI)=28.69, 141.06]. The values for chronic HCV-infected individuals were significantly different from those for non-HCV-infected individuals; the odds ratio was 53.43 (95% CI=23.33, 122.35). The positive ratio of the core protein was higher than that of F protein (rate difference=-38%, 95% CI=-42, -35%). CONCLUSION: We concluded that F protein elicits specific antibodies in most chronic HCV-infected individuals. Further, we confirmed the results of previous reports. The relationship between anti-F protein antibody and HCV coinfection still needs to be confirmed with further studies. Considering the high polymorphism rate of HCV, further studies are still needed for the selection of synthetic peptides from F protein that can coat the wells on microplates and serve as a commercial reagent.

[Application of liquid chromatography-mass spectrometry in the study of metabolic profiling of cirrhosis in different grades].

The metabolic profiles were obtained by high performance liquid chromatography combined with a LTQ Orbitrap XL mass spectrometer (HPLC-LTQ Orbitrap XL MS) platform to analyze serum specimens from the people of healthy control group and patients of hepatitis B virus (HBV)-induced cirrhosis. Then the data were analyzed with the pattern recognition methods and nonparametric test. The orthogonal partial least squares-discriminant analysis (OPLS-DA) mode (R2(Y) = 90.1%, Q2 = 66.7%) was constructed by the serum metabolic profiles of Child-Pugh grades A, B, C groups and a healthy control group in the training set and the good discrimination ability of this mode for the testing set was demonstrated with the accuracy of 93.8%. The corresponding specific metabolic biomarkers used to distinguish different cirrhosis grades were discovered, such as lysophosphatidylcholine (LPC), glycolchenodeoxycholic acid (GCDCA), cysteine, glycine, aminoadipic acid, pipecolic acid. The results suggest that the metabolic profiling of serum can be used to construct the discrimination mode and discover the metabolic biomarkers for the HBV-induced cirrhosis, which will support the diagnosis and evaluation of the HBV-induced cirrhosis.