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In the field of bone research, the importance of the function of skeletal macrophages (sMF) and their crucial role in immune homeostasis and bone regeneration has been extensively studied. The aim of the present systematic review was to summarize the role of sMF in bone fracture healing and to evaluate their potential for immunoregulatory therapy in bone regeneration. A systematic literature search of PubMed and Embase® was performed to retrieve studies on the role of sMF in bone injury repair. The Systematic Review Centre for Laboratory animal Experimentation tool was used to assess the risk of bias of the studies included. A total of four articles were included in the present review. A relatively high risk of bias was identified in the included articles as none of the assessors in these studies were blinded. sMF were defined by the surface markers F4/80+, Mac-2-/low, TRAP-, CD169+, Ly6G- and CD115low. All of the studies provided support for the essential role of sMF in intramembranous ossification or endochondral ossification during fracture healing. F4/80+Mac-2-CD169+ sMF are a promising therapeutic target for immunoregulatory therapy of bone repair due to their essential role in bone formation and homeostasis. Future studies aimed at profiling and modulating sMF to promote bone regeneration are required. [ABSTRACT FROM AUTHOR]

The aim of the present study was to explore the clinical value of urinary retinol-binding protein (RBP) level in the prognosis of cirrhotic ascites by assessment of the RBP levels prior to and following ascites treatment. The levels of urinary RBP, urinary microalbumin (mAlb), serum urea nitrogen (urea) and serum creatinine (Cr), and the estimated glomerular filtration rate (eGFR) were measured in 90 patients with cirrhosis and ascites hospitalized in a single institution between May 2011 and January 2012, and in 30 healthy controls. The levels of urinary mAlb, serum urea and serum Cr were higher in the cirrhotic patients compared with the healthy controls (P<0.05). Urinary RBP levels were significantly higher and eGFR was significantly lower in the liver cirrhosis group compared with the healthy control group (P<0.01). Urinary RBP, urinary mAlb, serum urea and serum Cr increased and eGFR decreased as the severity of the ascites increased (P<0.05). Urinary RBP was significantly higher in patients whose ascites did not respond or was refractory compared with those in whom it subsided (P<0.05), exhibiting a gradual increase over time in the former and a gradual reduction over time in the latter group (P<0.05). Increased urinary RBP and decreased eGFR in the early stage of cirrhosis ascites suggested impaired renal function, which serves a role in the process of ascites formation. These results indicated that urinary RBP is a sensitive indicator of early renal injury in patients with ascites due to cirrhosis and is closely associated with the progression of cirrhotic ascites. [ABSTRACT FROM AUTHOR]

The present study aimed to determine cyclooxygenase 2 (COX-2) and survivin expression levels in glioma tissues, and to investigate their association with clinicopathological factors and patient survival. Immunohistochemistry was performed to evaluate COX-2 and survivin expression levels in paraffin-embedded surgically resected tissues from 70 patients with glioma and 7 individuals with normal brain tissues. The association between COX-2 and survivin expression levels and clinicopathological features was investigated using the χ² test, and the survival time was analyzed using the Kaplan Meier method with log-rank test. COX-2 and survivin were overexpressed in glioma tissues, and higher expression levels were observed in glioma tissues of histological grades III-IV compared with those in grade I-II tumor tissues (P<0.05); however, the expression levels were not associated with gender, age, tumor size or location (P>0.05). There was a significant positive association between the expression levels of COX-2 and survivin in the glioma tissues. Additionally, COX-2 and survivin expression levels were significantly negatively correlated with the rate of survival. In conclusion, COX-2 and survivin expression is positively associated with the pathological grade of a glioma and may contribute to glioma tumorigenesis. Therefore, COX-2 and survivin may be sensitive predictors of a negative clinical prognosis for patients with glioma. [ABSTRACT FROM AUTHOR]

β-blockers are commonly used for the treatment of acute variceal bleeding in cirrhosis. Renin-angiotensin-aldosterone antagonists (angiotensin I-converting enzyme inhibitors, angiotensin receptor blockers and aldosterone antagonists) are potential therapies for portal hypertension. Several studies have compared the renin-angiotensin-aldosterone system (RAAS) inhibitor and β-blocker combination therapy vs. β-blocker monotherapy, with inconsistent results. The aim of the present study was to assess the efficacy of the RAAS inhibitor and β-blocker combination therapy vs. β-blocker monotherapy for hepatic vein pressure gradient (HVPG) reduction in cirrhosis. Studies were obtained using PubMed, Embase, Medline and Cochrane library databases up to July 2015, and the weighted mean difference (WMD) in HVPG reduction was used as a measure of treatment efficacy. In total, three studies (91 patients) were included. When compared to the β-blocker monotherapy, the RAAS inhibitor and β-blocker combination therapy resulted in a significant HVPG reduction [WMD 1.70; 95% confidence interval (CI): 0.52-2.88]. However, there was no significant difference in the heart rate reduction between the monotherapy and combination therapy groups (WMD -0.11; 95% CI: -3.51-3.29). In addition, no significant difference in the hemodynamic response was observed between the two groups (WMD 1.46; 95% CI: 0.93-2.30). In conclusion, the RAAS inhibitor and β-blocker combination therapy reduces portal hypertension significantly and to a greater extent than β-blocker monotherapy. Both therapies reduced the heart rate to similar levels; however, the RAAS inhibitor and β-blocker combination therapy reduced the mean arterial pressure to a greater extent. Due to the limited number of studies included, the data available do not allow a satisfactory comparison of adverse events. Moreover, further larger-scale trials are required in order to strengthen the results of the present study. [ABSTRACT FROM AUTHOR]

Fibronectin (FN) is a primary component of the mammary mesenchymal compartment and undergoes dramatic changes during breast cancer development. Increased FN expression is associated with an invasive and metastatic breast cancer phenotype. The present study demonstrated that FN causes an epithelial-mesenchymal transition (EMT)-like morphological change in MCF-7 breast cancer cells. FN stimulation caused the downregulation of epithelial markers E-cadherin and tight junction protein ZO-1, and the upregulation of mesenchymal markers N-cadherin and vimentin. Additionally, FN promoted cell migration and invasion in MCF-7 cells, with increased expression of calpain-2 and proteolysis of focal adhesion kinase 1 (FAK), indicating calpain activation. Notably, the FN induced changes in morphology and EMT markers were reversed with the treatment of calpain-specific inhibitors, calpain inhibitor I (N-acetyl-L-leucyl-L-leucyl-L-norleucinal), calpeptin and calpain inhibitor IV. Meanwhile, the effects of FN on cell migration and invasion, as well as FAK proteolysis were markedly suppressed by calpain inhibitors. Taken together, the results of the present study indicate that calpain plays an essential role in FN-induced EMT response, and that targeting calpain signaling may be a potential strategy to reduce breast cancer metastasis. [ABSTRACT FROM AUTHOR]

The purpose of the present article was to describe the diagnostic evaluation of, and surgical approaches to, lateral skull base tumors (LSBTs). The study is a retrospective review of 21 patients diagnosed with tumors that involve lateral skull base (8 with malignant diseases and 13 with benign lesions) who were surgically treated during a 8-year period. The transparotid-transmandibular (38%) was the most commonly performed surgical procedure, followed by the transmandibular (24%), the transmaxillary (24%), the transcervical approach (10%) and the combined approach (4%). The surgical procedures were uneventful and there were no postoperative mortalities. Complications were encountered in 12 cases, and morbidity was not remarkable during the perioperative stages. After an average follow-up of 46 months, only 1 of 14 patients with benign diseases had a recurrence following the resection of a pleomorphic adenoma. Of 7 patients with malignant tumors, 5 are alive with no evidence of disease. The majority of the benign lateral skull base tumors can be removed surgically with a low rate of complications and recurrence. However, malignant neoplasms carry a poor prognosis and a low rate of disease-free survival. [ABSTRACT FROM AUTHOR]

An increase in the use of iodinated contrast media, such as iohexol, iodixanol, iopamidol and iopromide, occasionally causes contrast-induced nephropathy (CIN) in patients undergoing coronary angiography (CAG) and/or percutaneous coronary intervention (PCI). The present study aimed to assess the effects of low levels of hemoglobin on the development of CIN in patients with normal renal function following CAG/PCI. A total of 841 consecutive patients undergoing CAG/PCI were divided into two groups: Patients with low levels of hemoglobin (male, <120 g/l; female, <110 g/l; n=156) and normal levels of hemoglobin (male, 120-160 g/l; female, 110-150 g/l; n=685). Multiple logistic regression analysis was performed to identify risk factors for CIN, which developed in 14.7% of patients with low levels of hemoglobin (relative risk, 3.07) and 5% of patients with normal levels of hemoglobin (P<0.01). Independent risk factors for developing CIN in patients with low levels of hemoglobin were a contrast media volume ≥200 ml, diuretic usage, low levels of hemoglobin and diabetes mellitus. For the patients with normal hemoglobin levels, the independent risk factors for developing CIN were a contrast media volume ≥200 ml and diuretic usage. The change in serum creatinine in patients with low levels of hemoglobin was significantly greater compared with patients with normal levels of hemoglobin (7.35±22.60 vs. 1.40±12.00; P<0.01). A similar incidence of developing CIN was observed when patients were administered each type of contrast media: Iohexol, iodixanol, iopamidol and iopromide. The optimal cut-off point at which the serum hemoglobin concentration resulted in a high probability of developing CIN was determined as 111.5 g/l in females and 115.5 g/l in males. In conclusion, low levels of hemoglobin were observed to be an independent risk factor for developing CIN. Patients with reduced hemoglobin levels should, therefore, be closely monitored prior to, and during, the administration of iodinated contrast media. [ABSTRACT FROM AUTHOR]

Primary liver cancer, which includes hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC) and fibrolamellar HCC, is one of the most common malignancies and the third leading cause of cancer-associated mortality, worldwide. Despite the development of novel therapies, the prognosis of liver cancer patients remains extremely poor. Thus, investigation of the genetic background and molecular mechanisms underlying the development and progression of this disease has gained significant attention. The Notch signaling pathway is a crucial determinant of cell fate during development and disease in several organs. In the liver, Notch signaling is involved in biliary tree development and tubulogenesis, and is also significant in the development of HCC and ICC. These findings suggest that the modulation of Notch pathway activity may have therapeutic relevance. The present review summarizes Notch signaling during HCC and ICC development and discusses the findings of recent studies regarding Notch expression, which reveal novel insights into its function in liver cancer progression. [ABSTRACT FROM AUTHOR]

Ovarian cancer is the most common cause of cancer-associated mortality in terms of gynecological malignancies, and is difficult to diagnose due to the absence of reliable biomarkers. To identify ovarian cancer-specific biomarkers, the present study used a Ph.D.-7 Phage Display Peptide Library to screen for ligands that selectively target HO-8910 ovarian cancer cells. Following 5 rounds of biopanning, the phage clone P2 was selected by enzyme-linked immunosorbent assay and DNA sequencing, and its characteristics were additionally validated by immunofluorescence and immunohistochemical assays. The results revealed the positive phage were enriched 92-fold following 5 rounds of biopanning, and the DNA sequence AAC CCG ATG ATT CGC CGC CAG (amino acid sequence, NPMIRRQ) was repeated most frequently (phage clones, P2, P3, P15, P30 and P54). Immunofluorescence and immunohistochemical assays revealed that the phage clone P2 was able to bind to ovarian cancer cells and tissues, and not those of cervical cancer. In conclusion, the peptide NPMIRRQ may be a potential agent for the diagnosis of ovarian cancer. [ABSTRACT FROM AUTHOR]

The aim of the present study was to explore the mechanism underlying the effects of a selective liver nitric oxide (NO) donor, O2-vinyl1-(pyrrolidin-1-yl)-diazen-1-ium-1,2-diolate (V-PYRRO/NO), on the gene expression of leukotriene C4 synthase (LTC4S) during hepatic ischemia/reperfusion (I/R). Adult male Sprague-Dawley rats were divided into 3 groups: Sham (control), I/R and V-PYRRO/NO + I/R groups. The liver was subjected to 1 h of partial hepatic ischemia followed by 5 h of reperfusion, saline or V-PYRRO/NO (1.06 μmol/kg/h) administered intravenously. The mRNA expression levels of LTC4S in rat liver tissue were examined by the reverse transcription-polymerase chain reaction method, the protein expression levels of nuclear factor-κB (NF-κB) p65, p50 and IκBα in liver cell lysates and nuclear extracts were detected by western blot analysis. Hepatic mRNA expression of LTC4S was lower in V-PYRRO/NO + I/R group compared to the I/R group. In addition, the protein expression levels of NF-κB p65 and p50 in the nucleus extract were lower in the V-PYRRO/NO + I/R group when compared with the I/R group. However, the IκBα protein in the 3 groups was not changed. Immunohistochemistry staining revealed that the I/R liver exhibited strong cytoplasmic and nuclear staining for NF-κB p65; however, the V-PYRRO/NO + I/R group liver presented slight cytoplasmic and nuclear staining. In conclusion, V-PYRRO/NO may downregulate LTC4S mRNA expression by inhibiting NF-κB activation independent of IκBα during hepatic I/R injury. [ABSTRACT FROM AUTHOR]

Pulmonary artery (PA) leiomyosarcoma (PAL) is a rare but extremely malignant tumor of the cardiovascular system, which is often misdiagnosed as pulmonary thrombo-embolism. Although the early detection and surgical resection improves patient survival, the benefits of adjuvant therapy are not well understood. The current study presents the case of a patient with primary PAL who underwent surgical resection along with three courses of chemotherapy. Despite these interventions, the patient experienced recurrence of the PAL within four months following treatment. The patient received localized radiotherapy and subsequently achieved a stable disease state. This case indicates that radiotherapy may offer a benefit to PAL patients, particularly those who do not respond to chemotherapy. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and the third leading cause of cancer-related mortality worldwide. Conflicting results have been reported regarding the use of serum Golgi protein 73 (GP73) as a promising serum marker for the diagnosis of HCC; therefore, the aim of the present study was to provide a systematic review of the diagnostic performance of GP73 for HCC. Following a systematic review of the relevant studies, a number of indices associated with the accuracy of the diagnostic performance of GP73, including the sensitivity and specificity, were pooled using Meta Disc 1.4 software. Data were presented as forest plots, and summary receiver operating characteristic (SROC) curve analysis was used to summarize the overall test performance. Eleven studies were included in this meta-analysis. The summary estimates for serum GP73 in diagnosing HCC were as follows: Sensitivity, 77% [95% confidence interval (CI), 75-79%]; specificity, 91% (95% CI, 90-92%); positive likelihood ratio, 4.34 (95% CI, 2.19-8.59); negative likelihood ratio, 0.30 (95% CI, 0.26-0.36) and diagnostic odds ratio, 15.78 (95% CI, 6.95-35.83). The area under the SROC curve was 0.8638, and the Q index was 0.7944. Significant heterogeneity was found. This meta-analysis indicates a moderate diagnostic value of GP73 in HCC; however, further studies with rigorous design, large sample size and multiregional cooperation are required. [ABSTRACT FROM AUTHOR]

To investigate the feasibility of the anti-mucin 1 (anti-MUC1/CD227) antibody in the fluorescent imaging of ovarian cancer, the CD227 antibody and a control IgG antibody were labeled with a near-infrared dye [Cy5.5-N-hydroxy-succinimide (NHS)] and a green dye (fluorescein-NHS). In vivo fluorescence images were obtained at 4, 12 and 36 h after injection of the probes into OVCAR3 tumor-bearing mice. The tumor to background ratios were calculated for both probes. Ex vivo fluorescence images were obtained following sacrifice at 36 h. After conjugation to Cy5.5 and fluorescein, the dual-color labeled CD227 probe (Ab-FL-Cy5.5) could be visualized by both green and near-infrared fluorescence. Uptake by the tumors was higher for the Ab-FL-Cy5.5 than for the IgG-Cy5.5 probe. All tumors could be visualized by in vivo imaging with an acceptable tumor to background ratio. Ex vivo studies demonstrated the advantages of using green fluorescence imaging to guide the resection of tumor tissues. These preliminary data indicate that the Ab-FL-Cy5.5 probe is promising for further tumor imaging applications and clinical translation. [ABSTRACT FROM AUTHOR]

This study was conducted to investigate survival and prognostic factors for extrahepatic cholangiocarcinoma (ECC) following surgical resection and evaluate the effects of postoperative adjuvant therapy (AT) on overall survival (OS). We retrospectively collected clinical and pathological data between March, 2008 and December, 2013. The Kaplan-Meier method and the COX regression model were used to evaluate the OS and prognostic factors of 105 postoperative ECC patients, of whom 32 had received AT. The patients were stratified into seven risk subgroups and the survival rates were compared within each subgroup between patients who received AT and those who did not. The results demonstrated a median OS of 17.6 months, with 1- and 3-year survival rates of 67.9 and 19.5%, respectively, for the entire cohort. On univariate analysis, preoperative cholangitis, non-R0 surgical margins, poor differentiation grade, stage 3/4 and lymphatic metastasis were identified as adverse prognostic factors. AT was not significantly associated with improved OS. However, the subgroup analysis revealed that the effect of AT was significant only in the lymphatic metastasis group (median OS, 21.6 vs. 10.4 months; and 3-year OS, 16.6 vs. 0%, respectively; P=0.02). The survival curves of the AT and non-AT groups were significantly different only for node-positive patients. The COX regression model identified lymphatic metastasis, surgical margins and AT as independent prognostic factors for ECC. A negative resection margin may reduce the mortality rate following surgery by 47%. By contrast, lymph node metastasis was associated with a 2.18-fold higher mortality rate for ECC patients. Postoperative AT contributed to a 0.45-fold mortality rate compared to non-AT ECC patients. Therefore, we concluded that AT is a favorable prognostic factor for ECC patients and it may prolong the survival of patients with lymphatic metastasis. Our data suggest that postoperative AT should be recommended for node-positive ECC patients. [ABSTRACT FROM AUTHOR]