Whole exome sequencing and proteomics-based investigation of the pathogenesis of coronary artery disease with diffuse long lesion.

OBJECTIVES: The long-term prognosis of patients with coronary artery disease (CAD) with diffuse long lesion underwent coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI) remains worse. Here, we aimed to identify distinctive genes involved and offer novel insights into the pathogenesis of diffuse long lesion. MATERIALS AND METHODS: Whole exome sequencing was performed on peripheral blood samples from 20 CAD patients with diffuse long lesion (CAD-DLL) and from 10 controls with focal lesion (CAD-FL) through a uniform pipeline. Proteomics analysis was conducted on the serum samples from 10 CAD-DLL patients and from 10 controls with CAD-FL by mass spectrometry. Bioinformatics analysis was performed to elucidate the involved genes, including functional annotation and protein-protein interaction analysis. RESULTS: A total of 742 shared variant genes were found in CAD-DLL patients but not in controls. Of these, 46 genes were identified as high-frequency variant genes (≥ 4/20) distinctive genes. According to the consensus variant site, 148 shared variant sites were found in the CAD-DLL group. The lysosome and cellular senescence-related pathway may be the most significant pathway in diffuse long lesion. Following the DNA-protein combined analysis, eight genes were screened whose expression levels were altered at both DNA and protein levels. Among these genes, the MAN2A2 gene, the only one that was highly expressed at the protein level, was associated with metabolic and immune-inflammatory dysregulation. CONCLUSIONS: Compared to individuals with CAD-FL, patients with CAD-DLL show additional variants. These findings contribute to the understanding of the mechanism of CAD-DLL and provide potential targets for the diagnosis and treatment of CAD-DLL.

Clinical Features, Treatment Modalities, and Outcomes of Elderly Thymoma Patients: A Propensity-Matched Study Based on the SEER Database.

INTRODUCTION: Thymoma is a common mediastinal tumor, but few studies have been performed in thymoma patients 80 years or older. This study aimed to analyze the clinical features, treatment modalities, and survival outcomes of thymoma patients at least 80 years old and compare these features to those of patients younger than 80 years old. METHOD: Data from thymoma patients in the Surveillance, Epidemiology and End Results database between 2000 and 2019 were selected. Clinical features, treatment modalities of the two age groups were compared. Survival rates were calculated by the Kaplan-Meier method and the log-rank test was used to compare survival rates between two groups. Propensity score matching was used based on whether surgery was performed. Univariate and multivariate Cox proportional-hazards regression analyses were performed to identify independent prognostic factors. RESULTS: Compared with the younger patients, the patients aged 80 years or older had a similar distribution of Masaoka-Koga tumor stage, a higher proportion of type A thymoma, and a lower recurrence rate in the early stage. In elderly patients after propensity score matching, the overall survival and cancer-specific survival were better in the surgery group with complete resection and compared with patients of different ages, elderly patients showed similar benefit from surgery as younger patients were observed. CONCLUSION: In thymoma patients aged 80 years or older, surgery still plays an important role in survival outcome. Compared with younger patients, older patients have unique clinical features.

Construction and validation of a nomogram based on the log odds of positive lymph nodes to predict cancer-specific survival in patients with small cell lung cancer after surgery.

Background: The lymph node ratio (LNR) is useful for predicting survival in patients with small cell lung cancer (SCLC). The present study compared the effectiveness of the N stage, number of positive LNs (NPLNs), LNR, and log odds of positive LNs (LODDS) to predict cancer-specific survival (CSS) in patients with SCLC. Materials and methods: 674 patients were screened using the Surveillance Epidemiology and End Results database. The Kaplan-Meier survival and receiver operating characteristic (ROC) curves were performed to address optimal estimation of the N stage, NPLNs, LNR, and LODDS to predict CSS. The optimal LN status group was incorporated into a nomogram to estimate CSS in SCLC patients. The ROC curve, decision curve analysis, and calibration plots were utilized to test the discriminatory ability and accuracy of this nomogram. Results: The LODDS model showed the highest accuracy compared to the N stage, NPLNs, and LNR in predicting CSS for SCLC patients. LODDS, age, sex, tumor size, and radiotherapy status were included in the nomogram. The results of calibration plots provided evidences of nice consistency. The ROC and DCA plots suggested a better discriminatory ability and clinical applicability of this nomogram than the 8th TNM and SEER staging systems. Conclusions: LODDS demonstrated a better predictive power than other LN schemes in SCLC patients after surgery. A novel LODDS-incorporating nomogram was built to predict CSS in SCLC patients after surgery, proving to be more precise than the 8th TNM and SEER staging.

Oncogenic roles and related mechanisms of the long non-coding RNA MINCR in human cancers.

Long non-coding RNAs (lncRNAs) play vital roles in regulating epigenetic mechanisms and gene expression levels, and their dysregulation is closely associated with a variety of diseases such as cancer. Several studies have demonstrated that lncRNAs are dysregulated during tumor progression. Recently, the MYC-induced long non-coding RNA MINCR, a newly identified lncRNA, has been demonstrated to act as an oncogene in different cancers, including gallbladder cancer, hepatocellular cancer, colorectal cancer, non-small cell lung cancer, oral squamous cell carcinoma, nasopharyngeal cancer, and glioma. Moreover, MINCR has been reported to act as a biomarker in the prognosis of patients with different cancers. In this review, we summarize and analyze the oncogenic roles of MINCR in a variety of human cancers in terms of its clinical significance, biological functions, cellular activities, and regulatory mechanism. Our analysis of the literature suggests that MINCR has potential as a novel biomarker and therapeutic target in human cancers.

Prognostic Assessment of Oxidative Stress-Related Genes in Colorectal Cancer and New Insights into Tumor Immunity.

Oxidative stress is crucial to the biology of tumors. Oxidative stress' potential predictive significance in colorectal cancer (CRC) has not been studied; nevertheless here, we developed a forecasting model based on oxidative stress to forecast the result of CRC survival and enhance clinical judgment. The training set was chosen from the transcriptomes of 177 CRC patients in GSE17536. For validation, 65 samples of colon cancer from GSE29621 were utilized. For the purpose of choosing prognostic genes, the expression of oxidative stress-related genes (OXEGs) was found. Prognostic risk models were built using multivariate Cox regression analysis, univariate Cox regression analysis, and LASSO regression analysis. The outcomes of the western blot and transcriptome sequencing tests were finally confirmed. ATF4, CARS2, CRP, GPX1, IL1B, MAPK8, MRPL44, MTFMT, NOS1, OSGIN2, SOD2, AARS2, and FOXO3 were among the 14 OXEGs used to build prognostic characteristics. Patients with CRC were categorized into low-risk and high-risk groups according on their median risk scores. Cox regression analysis using single and multiple variables revealed that OXEG-related signals were independent risk factors for CRC. Additionally, the validation outcomes from western blotting and transcriptome sequencing demonstrated that OXEGs were differently expressed. Using 14 OXEGs, our work creates a predictive signature that may be applied to the creation of new prognostic models and the identification of possible medication candidates for the treatment of CRC.

Identifying octogenarians with non-small cell lung cancer who could benefit from surgery: A population-based predictive model.

Background: As the population ages, there will be an increasing number of octogenarian patients with non-small cell lung cancer (NSCLC). In carefully selected elderly patients, surgery can improve long-term survival. To identify candidates who would benefit from surgery, we performed this study and built a predictive model. Materials and methods: Data from NSCLC patients over 80 years old were obtained from the Surveillance, Epidemiology and End Results database. A 1:1 propensity score matching was performed to balance the clinicopathological features between the surgery and non-surgery groups. Kaplan-Meier analyses and log-rank tests were used to assess the significance of surgery to outcome, and Cox proportional-hazards regression and competing risk model were conducted to determine the independent prognostic factors for these patients. A nomogram was built using multivariable logistic analyses to predict candidates for surgery based on preoperative factors. Results: The final study population of 31,462 patients were divided into surgery and non-surgery groups. The median cancer-specific survival time respectively was 53 vs. 13 months. The patients' age, sex, race, Tumor, Node, Metastasis score, stage, chemotherapy use, tumor histology and nuclear grade were independent prognostic factors. Apart from race and chemotherapy, other variates were included in the predictive model to distinguish the optimal surgical octogenarian candidates with NSCLC. Internal and external validation confirmed the efficacy of this model. Conclusion: Surgery improved the survival time of octogenarian NSCLC patients. A novel nomogram was built to help clinicians make the decision to perform surgery on elderly patients with NSCLC.

Prognostic and clinicopathological significance of SR-B1 in solid tumors: A meta-analysis.

BACKGROUND: The expression of cell surface receptors is abnormal in malignant tumors. The scavenger receptor class B type I (SR-B1) is an integral membrane glycoprotein receptor that facilitates the selective uptake of cholesterol by malignant cells. Accumulated studies investigated the prognostic role of SR-B1 in many solid tumors, such as breast cancer, lung cancer and so on. However, the conclusions remain undefined. Therefore, we conducted this meta-analysis to obtain more accurate evaluation of prognostic significance of SR-B1 in solid tumors. MATERIALS AND METHODS: We searched PubMed, Embase, Web of science and Cochrane library for eligible studies published before November 2018. The included studies investigated the association between the SR-B1 level and clinicopathological features including survival outcomes in solid tumors. Hazard ratios (HRs) with 95% confidence intervals (CIs) were adopted to assess the survival outcomes and odds ratio (ORs) with 95% confidence intervals (CIs) were pooled to evaluated the clinicopathological features. RESULTS: A total of 10 studies involving 2585 patients were included in this meta-analysis. The results showed that low SR-B1 level was significantly correlated with earlier tumor grade (pooled OR = 2.09, 95%CI = 1.28-3.43, P = 0.001), less nodal involvement (pooled OR = 2.07, 95%CI = 1.43-3.0, P < 0.001), less distant metastasis (OR = 19.8, 95%CI = 2.58-151.65, P = 0.004), smaller tumor size (OR = 2.34, 95%CI = 1.53-3.57, P < 0.001), earlier TNM stage (OR = 3.77, 95%CI = 1.67-8.48, P = 0.001), lower recurrence (HR = 1.98, 95%CI = 1.57-2.49, P = 0.000), and better OS (HR = 1.99, 95%CI = 1.70-2.31, P = 0.000). CONCLUSION: The low expression of SR-B1 was significantly associated with better clinicopathological status and longer survival in patients with solid tumors. SR-B1 might act as a promising prognostic biomarker for solid tumors.

The choice of dissection or preservation of the inferior pulmonary ligament after an upper lobectomy: a systematic review and meta-analysis.

BACKGROUND: The necessity of the inferior pulmonary ligament (IPL) dissection after an upper lobectomy remains controversial. This meta-analysis aimed to evaluate whether this accessional procedure could reduce the postoperative complications and improve outcomes. METHODS: PubMed, Embase, Ovid, Cochrane Library, CBM, and CNKI databases were searched for the relevant studies which compared the dissection with preservation of IPL during the upper lobectomy. The Review Manager 5.3 software was used for this meta-analysis. RESULTS: Three RCTs and five CCTs were included in this meta-analysis. These studies contained a total of 610 patients, in which 315 patients received a pulmonary ligament dissection (group D) after the upper lobectomy, while the other 295 patients preserved the pulmonary ligament (group P). No significant difference was demonstrated between the group D and group P in terms of drainage time after surgery (MD 0.14, 95%CI - 0.05 to 0.33, P = 0.15), rate of postoperative dead space (OR 1.33, 95%CI 0.72 to 2.46, P = 0.36), rate of postoperative complications (OR 1.20, 95%CI 0.66 to 2.19, P = 0.56). However, the pooled comparison revealed a greater change of the right main bronchial angle (MD 5.00, 95%CI 1.68 to 8.33, P = 0.003) in group D compared with group P, indicated that the dissection of IPL may lead to a greater distortion of bronchus. CONCLUSIONS: This meta-analysis confirmed that the dissection of IPL do not effectively reduce the postoperative complications and improve the prognosis. Therefore, it is not necessary to dissect the IPL after an upper lobectomy.

Prognostic significance of TRIM59 for cancer patient survival: A systematic review and meta-analysis.

BACKGROUND: The family of tripartite motif (TRIM) proteins, which includes 80 known TRIM protein genes in humans, play a key role in cellular processes. TRIM59, a member of the TRIM family of proteins, has been reported to be involved in the carcinogenesis of multiple types of tumors. However, the prognostic value of TRIM59 in the survival of tumor patients remains controversial. We therefore conducted a meta-analysis to assess the prognostic significance of TRIM59 in cancer patients. MATERIALS AND METHODS: PubMed, Embase, VIP, CNKI and Wanfang Data were searched for eligible reports published before September 30, 2018. The hazard ratio (HR) and 95% confidence intervals (CIs) were adopted to estimate the association between TRIM59 and overall survival (OS). RESULTS: Six studies with 1584 patients were included to assess the effect. The results showed that high levels of TRIM59 were significantly associated with poor OS in cancer patients (HR = 1.43, 95%CI: 1.24-1.66, P < .001), indicating that higher TRIM59 expression could be an independent prognostic factor for poor survival in cancer patients. CONCLUSION: Our meta-analysis suggests that higher TRIM59 expression predicts poor prognosis in cancer patients, and it may therefore serve as a promising prognostic factor.

Analysis of sternal healing after median sternotomy in low risk patients at midterm follow-up: retrospective cohort study from two centres.

BACKGROUND: For low risk patients undergoing median sternotomies, no midterm follow-up studies involving sternal healing have been conducted. In this study we evaluated sternal healing in low risk patients by chest CT scan and the risk factors associated with poor healing were analyzed. METHODS: Patients who underwent sternal median incision heart surgery from September 2014 to March 2015 were recruited. The clinical information of these patients during hospitalization was collected, and the CT scan data were submitted to the two chief physicians of the Radiology Department for radiographical sternal healing score determination. Based on the method of wound closure, the patients were divided into sternum plate (Plates) and wire groups (Wires). RESULTS: Forty-four patients were recruited. The mean CT examination time was 17.27 ± 2.30 months postoperatively. Twenty-nine (65.9%) patients met the criteria for radiographic sternal healing. Three segments, including the aortopulmonary window, the main pulmonary artery, and the aortic root, had healed less in comparison to the manubrium segment. Compared to patients in whom 6-7 metal wires were used for sternal closure, healing of the lower sternum was worse in patients in whom five wires were used, but the difference in healing was not statistically significant. Univariate analysis of sternal healing showed that patient age was a risk factor for sternal non-healing. When the patient age was > 45 years, the predicted risk of radiographic sternal non-union was 1.833 (95% CI: 1.343-2.503). CONCLUSIONS: At the mid-term follow-up, 65.9% of patients undergoing median sternotomies demonstrated radiographic sternal healing. Age, but not closure device, was a risk factor for sternal non-healing in low risk patients. Use of more wires had a positive impact on sternal healing. TRIAL REGISTRATION: researchregistry4918, registered 28 May 2019, retrospectively registered.

Systematic Review and Meta-Analysis of the Prognostic Value of Serum High-Density Lipoprotein Cholesterol Levels for Solid Tumors.

Numerous studies have demonstrated that serum high-density lipoprotein cholesterol (HDL-C) levels correlate strongly with cancer patient survival. However, other studies have had the opposite results. We therefore conducted a systematic review and meta-analysis to assess the prognostic value of HDL-C levels in people with cancer. We searched PubMed, Embase, and the Cochrane Library (last update by December 28, 2017) for studies evaluating the effect of serum HDL-C levels on cancer patient prognosis. Data from 25 studies covering13,140 patients were included. Combined hazard ratios (HRs) for overall survival (OS) and disease-free survival (DFS) were assessed using fixed-effects and random-effects models. High serum HDL-C levels were associated with better OS (pooled HR = 0.70; 95% confidence interval (CI) (0.60-0.82). In the subgroup, the relative high level of HDL-C yielded a favorable outcome in most of tumor types. However, in the nasopharyngeal carcinoma subgroup, the correlation was not significant (combined HR = 1.31; 95% CI (0.91-1.90)). High serum HDL-C levels were associated with better DFS (pooled HR = 0.64; 95% confidence interval (CI) (0.50-0.81)). This meta-analysis demonstrates that high serum HDL-C levels are associated with better OS in patients with solid tumors, but not nasopharyngeal carcinoma; and high serum HDL-C levels are associated with better DFS.

Apolipoprotein M induces inhibition of inflammatory responses via the S1PR1 and DHCR24 pathways.

Apolipoprotein M (ApoM) is a type of apolipoprotein. It is well known that high­density lipoprotein (HDL) decreases inflammatory responses via the apoM­sphingosine­1­phosphate (S1P) pathway. The present study further investigated the importance of ApoM in the inhibitory effects of HDL on inflammation. Mice with an apoM gene deficiency (apoM­/­) were employed to investigate the effects of ApoM on the expression of interleukin­1ß (IL­1ß), monocyte chemotactic protein­1 (MCP­1), S1P receptor­1 (S1PR1) and 3ß­hydroxysterol Δ­24­reductase (DHCR24), as compared with in wild­type mice (apoM+/+). Furthermore, cell culture experiments were performed using a permanent human hybrid endothelial cell line (EA.hy926). Cells were cultured in the presence of recombinant human apoM (rec­apoM) or were induced to overexpress apoM (apoMTg); subsequently, cells were treated with tumor necrosis factor­α (TNF­α), in order to investigate the effects of ApoM on IL­1ß and MCP­1. The results demonstrated that the mRNA expression levels of IL­1ß and MCP­1 were significantly higher in the liver following administration of lipopolysaccharide in apoM­/­ mice compared with in apoM+/+ mice. In cell culture experiments, when cells were pre­cultured with rec­apoM or were engineered to overexpress apoM (apoMTg), they exhibited decreased expression levels of IL­1ß and MCP­1 following TNF­α treatment compared with in normal apoM­expressing cells (apoMTgN). Furthermore, the mRNA expression levels of IL­1ß and MCP­1 were significantly elevated following addition of the S1PR1 inhibitor W146, but not by the scavenger receptor class B type I inhibitor, block lipid transport­1 (BLT­1), in apoMTg cells prior to TNF­α treatment. Conversely, there were no differences in these inflammatory biomarkers under the same conditions in apoMTgN cells. The mRNA expression levels of DHCR24 were significantly reduced by the addition of BLT­1 prior to TNF­α treatment in apoMTg cells; however, there was no difference in the expression of this inflammatory biomarker in apoMTgN cells. In conclusion, ApoM displayed inhibitory effects against the inflammatory response in vivo and in vitro; these effects may be induced via the S1PR1 and DHCR24 pathways.

Cauda equine syndrome as the primary symptom of leptomeningeal metastases from lung cancer: a case report and review of literature.

Cauda equine syndrome (CES) is a neurological condition caused by compression of the cauda equine. Here, we demonstrate a case of CES as the primary symptom of leptomeningeal metastases from non-small cell lung carcinoma without brain metastases. A 59-year-old male suffered progressive lower extremity motor dysfunction, urinary dysfunction, and lower extremity sensory dysfunction. He was clinically diagnosed with CES. Nuclear magnetic resonance imaging demonstrated several vague nodules in the area of conus medullaris and cauda equine, without lumbar or thoracic herniated discs. The serum carcinoembryonic antigen concentration was 191.20 ng/mL. The conclusion following positron emission tomography-computed tomography was a right upper lung malignant tumor with mediastinal lymph node metastasis and cauda equina metastasis. Pathologic diagnosis was of primary adenocarcinoma of the lung by bronchoscopic biopsy. EML4-ALK fusion and EGFR mutations were absent, and thus the patient received chemotherapy. However, symptoms of intracranial hypertension arose 1 month later, and the patient died 3 months postadmission. Emerging CES may be a sign of metastasis of a malignant tumor, presenting an extremely challenging condition, especially for patients with lung cancer. Positron emission tomography-computed tomography is a fairly effective technique to make the diagnosis.

Role of TLR4 as a prognostic factor for survival in various cancers: a meta-analysis.

BACKGROUND: Accumulating evidence showed that high expression of toll like receptor 4 (TLR4) was significantly associated with the outcome of patients with solid cancers. However, other studies failed to draw a similar conclusion. Thus, a systematic meta-analysis was performed to assess the prognostic value of TLR4 in solid tumors. RESULTS: Data from 15 studies and 1294 patients were enrolled. Among the 15 studies, 14 studies demonstrated the association between overall survival(OS) and TLR4 expression, and 7 studies described the relationship between disease-free survival(DFS) and TLR4 expression. High expression of TLR4 was significantly associated with poor OS (pooled hazard ratio (HR) = 2.05; 95% confidence interval (CI) (1.49, 2,49), P < 0.001). The results of meta regression analysis indicated that the subgroups of ethnic (PD = 0.924), tumor type (PD = 0.669), HR obtained method (PD = 0.945), analysis type (PD = 0.898), and cut-off value(PD = 0.835) were not the resource of heterogeneity. Moreover, patients with elevated TLR4 had a significantly worse DFS (pooled HR = 1.79; 95% CI (1.11, 2.88), P < 0.05). MATERIALS AND METHODS: We searched PubMed, Embase and the Cochrane Library (last update by April 18, 2017) to identify literatures evaluating the value of TLR4 in cancer patients. Combined hazard ratios (HRs) for OS and DFS were assessed using fixed-effects models and random effects models respectively. CONCLUSIONS: The meta-analysis suggests that elevated expression of TLR4 is associated with poor OS and shorter DFS of patients with solid tumors. The results indicate that TLR4, as a novel prognostic biomarker in solid tumors, could potentially help to improve treatment decision-making of solid tumors in clinical.

Hyperglycemia-induced downregulation of apolipoprotein M expression is not via the hexosamine pathway.

BACKGROUND: We previously demonstrated that hyperglycemia could suppress apolipoprotein M (apoM) synthesis both in vivo and in vitro; however, the mechanism of hyperglycemia-induced downregulation of apoM expression is unknown yet. METHODS: In the present study we further examined if hexosamine pathway, one of the most important pathways of glucose turnover, being involved in modulating apoM expression in the hyperglycemia condition. We examined the effect of glucosamine, a prominent component of hexosamine pathway and intracellular mediator of insulin resistance, on apoM expression in HepG2 cells and in rat's models. In the present study we also determined apolipoprotein A1 (apoA1) as a control gene. RESULTS: Our results demonstrated that glucosamine could even up-regulate both apoM and apoA1 expressions in HepG2 cell cultures. The glucosamine induced upregulation of apoM expression could be blocked by addition of azaserine, an inhibitor of hexosamine pathway. Moreover, intravenous infusion of glucosamine could enhance hepatic apoM expression in rats, although serum apoM levels were not significantly influences. CONCLUSIONS: It is concluded that both exogenous and endogenous glucosamine were essential for the over-expression of apoM, which may suggest that the increased intracellular content of glucosamine does not be responsible for the depressed apoM expression at hyperglycemia condition.

Endoscopic closure of gastric tube perforations with titanium clips: a four-case report.

Perforation of a gastric tube is a rare yet lethal complication after esophagectomy for esophageal cancer treatment. Currently, over-the-scope clip (OTSC) is an effective way to treat gastric tube perforation. Due to the lack of OTSCs, we invented an alternative method composed of a titanium clip and gastroscope. The aim of this study was to describe this novel endoscopic device in the treatment of gastric tube perforation. We used a titanium clip system to treat 4 male patients (range, 53 to 77 years with gastric tube perforation. After the location of the perforation was identified by gastroscope, a titanium endoscopic clip was used to close the perforation. Successful closure of the gastric tube perforation was achieved in three patients while in one patient this failed due to his refusal to undergo reoperation. No postoperative complication was found in the three patients whose perforations were closed and the patient who refused reoperation died due to the reoccurrence of his esophago-cardiac carcinoma. The endoscopic system composed of titanium clip and gastroscope proved to be an efficient and effective device in the treatment of the patients with gastric tube perforations.

ABCA1 upregulating apolipoproein M expression mediates via the RXR/LXR pathway in HepG2 cells.

We have previously reported that liver X receptor (LXR) agonist, TO901317, could significantly inhibit hepatic apolipoprotein M (apoM) expression. It has been reported that TO901317 could activate the ATP-binding cassette transporter A1 (ABCA1) that mediates cholesterol efflux to the lipid-poor apoAI, which is an essential step for the high-density lipoprotein (HDL) formation. It is unknown if ABCA1 may regulate hepatic apoM expression. In the present study, HepG2 cells were cultured with the synthetic LXR agonists, TO901317 or GW3965 in the presence or absence of ABCA1 antagonist, disodium 4,4'-diisothiocyanatostilbene- 2,2'-disulfonate (DIDS). The mRNA levels of ABCA1, apoM and liver receptor homolog-1 (LRH-1) determined by the real-time RT-PCR. It demonstrated that both TO901317 and GW3965 could significantly enhance ABCA1 expression, and simultaneously, inhibit LRH1 expression. However, TO901317 alone could significantly inhibit apoM expression, while GW3965 alone did not influence apoM expression. ABCA1 antagonist, DIDS, have no effects on GW3965 induced upregulation of ABCA1 and downregulation of LRH1. However, apoM mRNA level was significantly decreased when the cells cultured with GW3965 together with DIDS. The present study demonstrated that apoM expression could be elevated by ABCA1 via the RXR/LXR pathway and LRH1 does not involve in the regulation of apoM by the activation of ABCA1, although the direct regulative pathway(s) between ABCA1 and apoM gene is still unknown yet. The detailed mechanism needs further investigation.

Immunochemical staining of MT2-MMP correlates positively to angiogenesis of human esophageal cancer.

Matrix metalloproteinases (MMPs) play an important role in the pathological processes of degradation of extracellular matrix and destruction of basement membrane, which leads to tumor invasion and metastasis. In the present study, we investigated membrane-type 2 MMP (MT2-MMP) expression pattern in esophageal cancer tissues collected from 103 patients, and explored MT2-MMP expression pattern in correlation to patients' clinicopathological features, intratumoral angiogenesis and postoperative prognoses. The intensity of immunochemical staining of MT2-MMP was significantly positively correlated to the intratumoral angiogenesis of esophageal cancer tissues. Positive MT2-MMP immunoreactions were found in 85.4% of total tumor sections, whereas none or very weak MT2-MMP staining occurred in normal esophageal tissues. In addition, MT2-MMP immunochemical intensities were significantly correlated to tumor size, but not to patient's gender, age, invasion depth, lymph node metastasis and distant metastasis. Moreover, MT2-MMP levels could not be applied for predicting patients' survival rate although the H-score cut-off value showed the overall survival rate of patients with low MT2-MMP protein level to be better than those with high MT2-MMP protein level.