16 research outputs found

    TFPI-2 is a putative tumor suppressor gene frequently inactivated by promoter hypermethylation in nasopharyngeal carcinoma

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Epigenetic silencing of tumor suppressor genes play important roles in NPC tumorgenesis. Tissue factor pathway inhibitor-2 (TFPI-2), is a protease inhibitor. Recently, <it>TFPI-2 </it>was suggested to be a tumor suppressor gene involved in tumorigenesis and metastasis in some cancers. In this study, we investigated whether <it>TFPI-2 </it>was inactivated epigenetically in nasopharyngeal carcinoma (NPC).</p> <p>Methods</p> <p>Transcriptional expression levels of <it>TFPI-2 </it>was evaluated by RT-PCR. Methylation status were investigated by methylation specific PCR and bisulfate genomic sequencing. The role of <it>TFPI-2 </it>as a tumor suppressor gene in NPC was addressed by re-introducing <it>TFPI-2 </it>expression into the NPC cell line CNE2.</p> <p>Results</p> <p><it>TFPI-2 </it>mRNA transcription was inactivated in NPC cell lines. <it>TFPI-2 </it>was aberrantly methylated in 66.7% (4/6) NPC cell lines and 88.6% (62/70) of NPC primary tumors, but not in normal nasopharyngeal epithelia. <it>TFPI-2 </it>expression could be restored in NPC cells after demethylation treatment. Ectopic expression of TFPI-2 in NPC cells induced apoptosis and inhibited cell proliferation, colony formation and cell migration.</p> <p>Conclusions</p> <p>Epigenetic inactivation of <it>TFPI-2 </it>by promoter hypermethylation is a frequent and tumor specific event in NPC. <it>TFPI-2 </it>might be considering as a putative tumor suppressor gene in NPC.</p

    Sedimentary diagenesis of rudist shoal and its control on reservoirs: A case study of Cretaceous Mishrif Formation, H Oilfield, Iraq

    No full text
    Based on the core, cast thin section, whole rock analysis, conventional physical properties and high pressure mercury intrusion test, the sedimentary diagenesis characteristics of rudist shoal in Cretaceous Mishrif Formation of H Oilfield, Iraq and its control on the reservoir were studied. The rudist shoal of the Mishrif Formation develops in the high-stand systems tract and is distributed in the high places of paleogeomorphology on the edge of platform with strong hydrodynamic force. According to the relative sea level changes, lithologic evolution and sedimentary structure characteristics of the rudist shoal, the single rudist shoal is divided into four lithologic sections: A, B, C and D, that is, low-angle cross-bedding pelletoids-rudist packstone, low-angle cross-bedding and parallel bedding arene-rudist grainstone, parallel bedding rudist gravel limestone, and horizontal bedding carbonaceous mudstone. The complete sedimentary sequence of a single rudist shoal is often disrupted. Several rudist shoals superimpose to form thick rudist shoal sediment. The single rudist shoal thickness and lithologic sections assemblage change regularly in vertical direction. The rudist shoal has the characteristics of “strong dissolution, weak cementation and strong compaction”, forming pore-type reservoir with intergranular pores, intergranular dissolved pores, mold pores, and dissolved pores. With mainly coarse pore throats larger than 5 μm, the reservoir is of medium-high porosity and high permeability. There is lithological reverse cycles inside single shoals and between single shoals, with content of mud crystals decreasing from the bottom to the top, dissolution increasing, cementation decreasing in strength, pore throats getting larger, and physical properties turning better. The rudist shoal of MB2-1 at the top of the high-stand systems tract has the largest thickness, moreover, subject to the strongest atmospheric freshwater leaching, this layer has the most significant dissolution and the largest pore throat, so it is the best reservoir of the Mishrif Formation. Key words: Iraq, Cretaceous, rudist shoal, sedimentary process, diagenetic evolution, reservoir characteristic

    Development and validation of web-based dynamic nomograms predictive of disease-free and overall survival in patients who underwent pneumonectomy for primary lung cancer

    No full text
    Background The tumour-node-metastasis (TNM) staging system is insufficient to precisely distinguish the long-term survival of patients who underwent pneumonectomy for primary lung cancer. Therefore, this study sought to identify determinants of disease-free (DFS) and overall survival (OS) for incorporation into web-based dynamic nomograms. Methods The clinicopathological variables, surgical methods and follow-up information of 1,261 consecutive patients who underwent pneumonectomy for primary lung cancer between January 2008 and December 2018 at Sun Yat-sen University Cancer Center were collected. Nomograms for predicting DFS and OS were built based on the significantly independent predictors identified in the training cohort (n = 1,009) and then were tested on the validation cohort (n = 252). The concordance index (C-index) and time-independent area under the receiver-operator characteristic curve (AUC) assessed the nomogram’s discrimination accuracy. Decision curve analysis (DCA) was applied to evaluate the clinical utility. Results During a median follow-up time of 40.5 months, disease recurrence and death were observed in 446 (35.4%) and 665 (52.7%) patients in the whole cohort, respectively. In the training cohort, a higher C-reactive protein to albumin ratio, intrapericardial pulmonary artery ligation, lymph node metastasis, and adjuvant therapy were significantly correlated with a higher risk for disease recurrence; similarly, the independent predictors for worse OS were intrapericardial pulmonary artery and vein ligation, higher T stage, lymph node metastasis, and no adjuvant therapy. In the validation cohort, the integrated DFS and OS nomograms showed well-fitted calibration curves and yielded good discrimination powers with C-index of 0.667 (95% confidence intervals CIs [0.610–0.724]) and 0.697 (95% CIs [0.649–0.745]), respectively. Moreover, the AUCs for 1-year, 3-year, and 5-year DFS were 0.655, 0.726, and 0.735, respectively, and those for 3-year, 5-year, and 10-year OS were 0.741, 0.765, and 0.709, respectively. DCA demonstrated that our nomograms could bring more net benefit than the TNM staging system. Conclusions Although pneumonectomy for primary lung cancer has brought encouraging long-term outcomes, the constructed prediction models could assist in precisely identifying patients at high risk and developing personalized treatment strategies to further improve survival

    Lack of association between cigarette smoking and Epstein Barr virus reactivation in the nasopharynx in people with elevated EBV IgA antibody titres

    No full text
    Abstract Background Subjects with elevated Epstein-Barr virus (EBV) immunoglobulin A (IgA) titers have a higher risk of developing nasopharyngeal carcinoma (NPC), indicating that reactivation of EBV in the local mucosa might be important for NPC carcinogenesis. Cigarette smoking appears to be one of the environmental risk factors for NPC. However, it remains unclear whether smoking-induced nasopharyngeal carcinogenesis acts through reactivating EBV in the nasopharyngeal mucosa. Therefore, this study aims to investigate the association between cigarette smoking and nasopharyngeal EBV reactivation in a NPC high-risk population. Methods A NPC high-risk cohort study, established from a population-based NPC screening program of 22,816 subjects, consisted of 1045 subjects with elevated serum IgA antibodies against EBV viral capsid antigen (VCA/IgA). Among high-risk subjects, information on detailed cigarette smoking history was collected among 313 male subjects. The associations between cigarette smoking and EBV antibody levels, EBV DNA load of the nasopharynx were analyzed. Results No significant association was observed between either nasopharyngeal EBV DNA load or serum VCA/IgA titers and smoking status, age at smoking initiation, daily smoking intensity, smoking duration, cigarette type, or pack-years of smoking. Cigarette smoking characteristics in all subgroups did not correlate with nasopharyngeal EBV DNA positivity or EBV VCA/IgA seropositivity. Conclusions In a population at high risk of NPC, our study suggests that cigarette smoking is neither associated with nasopharyngeal EBV DNA load nor serum VCA/IgA antibody level. Smoking-associated NPC carcinogenesis may act through other mechanisms than reactivating nasopharyngeal EBV replication

    Nasopharyngeal Epstein-Barr Virus Load: An Efficient Supplementary Method for Population-Based Nasopharyngeal Carcinoma Screening.

    No full text
    Serological detection of Epstein-Barr virus (EBV) antibodies is frequently used in nasopharyngeal carcinoma (NPC) mass screening. However, the large number of seropositive subjects who require close follow-up is still a big burden. The present study aimed to detect the nasopharyngeal EBV load in a high-risk population seropositive for antibodies against EBV, as well as to examine whether assay for nasopharyngeal EBV DNA load might reduce the number of high-risk subjects for follow-up and improve early detection of NPC. A prospective and population-based cohort study was conducted in southern China from 2006 through 2013. Among 22,186 participants, 1045 subjects with serum immunoglobulin A (IgA) antibodies against viral capsid antigen (VCA) titers ≥ 1:5 were defined as high-risk group, and were then followed-up for NPC occurrence. Qualified nasopharyngeal swab specimens were available from 905 participants and used for quantitative PCR assay. Our study revealed that 89% (802/905) subjects showed positive EBV DNA in nasopharyngeal swab. The nasopharyngeal EBV load in females was higher than that in males. The nasopharyngeal EBV load increased with increasing serum VCA/IgA titers. Eight cases of newly diagnosed NPC showed an extremely elevated EBV load, and 87.5% (7 of 8 patients) were early-stage NPCs. The EBV loads of 8 NPCs were significantly higher than those of 897 NPC-free subjects (mean, 2.8 × 10(6) copies/swab [range 4.8 × 10(4)-1.1 × 10(8)] vs. 5.6 × 10(3) [range 0-3.8 × 10(6)]). Using mean EBV load in NPC-free population plus two standard deviations as cut-off value, a higher diagnostic performance was obtained for EBV load test than serum VCA/IgA test (area under ROC, 0.980 vs 0.895). In conclusion, in a prospective and population-based study we demonstrated that an additional assay of EBV load in the nasopharynx among high-risk individuals may reduce the number of subjects needed to be closely followed up and could serve as part of a NPC screening program in high-risk populations

    EBV load and VCA/IgA titers in males and females.

    No full text
    <p>Nasopharyngeal EBV load and serum VCA/IgA titers by gender and age groups. (a) Mean EBV load in females was higher than that of males by different age groups; EBV load increased with age in both genders. (b) There was no difference in VCA/IgA titers between males and females in different age groups; VCA/IgA titers increased with age in both males and females.</p

    Nasopharyngeal EBV DNA load and serum VCA/IgA titers in seropositive high-risk population.

    No full text
    <p>EBV, Epstein-Barr virus; VCA, viral capsid antigen; SD, standard deviation; (+), positive; (-), negative.</p><p>Nasopharyngeal EBV DNA load and serum VCA/IgA titers in seropositive high-risk population.</p
    corecore