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Introduction: Triple-negative breast cancer (TNBC) is a heterogeneous disease with no definitive prognostic markers. As a major component of tight junctions, claudins (CLDNs) presumably play an important role in carcinogenesis and progression of breast cancer. This study was aimed at determining the relationship between the expression of CLDNs and the clinical outcomes of TNBCs., Materials and Methods: The surgical specimens of primary breast tumors from a consecutive cohort of 173 TNBC patients were retrospectively collected. The membranous expression of CLDN1, CLDN2, CLDN4, and CLDN7 was measured by immunohistochemistry. Then, the associations between CLDN expression, clinicopathological features, and clinical outcomes were assessed., Results: Positive CLDN1, CLDN2, CLDN4, and CLDN7 membrane expression was detected in 44.5%, 54.9%, 76.9%, and 73.4% of the cohort specimens, respectively. A lack of CLDN1 expression was related to only lymph node metastasis (P = 0.014). The rate of CLDN4-positive tumors was significantly increased in tumors of a higher grade (P = 0.003). Importantly, negative CLDN1 expression was associated with worse relapse-free survival (RFS) in both lymph node positive (LN+) and negative (LN-) cases (both P<0.001). Similarly it was also associated with shorter overall survival (OS)(P = 0.003 in LN+ cases; P = 0.018 in LN- cases). In the LN+ subgroup, CLDN2-negative cases had a significantly higher risk of recurrence (P = 0.008). Multivariate analysis revealed that negative CLDN1 expression was an independent prognostic factor for high risk of both recurrence and death (HR 5.529, 95% CI 2.664-11.475, P<0.001; HR 3.459, 95% CI 1.555-7.696, P = 0.002). However, neither CLDN4 nor CLDN7 expression was associated with survival., Conclusion: In TNBC, the CLDN1-negative phenotype predicts a high risk of recurrence and death. The absence of CLDN1 expression is strongly suggested to be an independent adverse prognostic factor in this heterogeneous subtype of breast cancer.

Purpose: 99mTc-3PRGD2, a promising tracer targeting integrin receptor, may serve as a novel tumor-specific agent for single photon emission computed tomography (SPECT). A multi-center study was prospectively designed to evaluate the diagnostic accuracy of 99mTc-3PRGD2 imaging for bone metastasis in patients with lung cancer in comparison with the conventional 99mTc-MDP bone scan., Methods: The patients underwent whole-body scan and chest tomography successively at both 1 h and 4 h after intravenous injection of 11.1 MBq/Kg 99mTc-3PRGD2. 99mTc-MDP whole-body bone scan was routinely performed within 1 week for comparison. Three experienced nuclear medicine physicians blindly read the 99mTc-3PRGD2 and 99mTc-MDP images. The final diagnosis was established based on the comprehensive assessment of all available data., Results: A total of 44 patients (29 male, 59±10 years old) with suspected lung cancer were recruited from 4 centers. Eighty-nine bone lesions in 18 patients were diagnosed as metastases and 23 bone lesions in 9 patients were benign. In a lesion-based analysis, 99mTc-3PRGD2 imaging demonstrated a sensitivity, specificity, and accuracy of 92.1%, 91.3%, and 92.0%, respectively. The corresponding diagnostic values for 99mTc-MDP bone scan were 87.6%, 60.9%, and 82.1%, respectively in the same patients. 99mTc-MDP bone scan had better contrast in most lesions, whereas the 99mTc-3PRGD2 imaging seemed to be more effective to exclude pseudo-positive lesions and detect bone metastases without osteogenesis., Conclusion: 99mTc-3PRGD2 is a novel tumor-specific agent based on SPECT technology with a promising value in diagnosis of bone metastasis in patients with lung cancer., Trial Registration: ClinicalTrials.gov NCT01737112.

Background: Few studies have investigated the association between body mass index (BMI) and breast cancer with consideration to estrogen/progesterone/human epidermal growth factor type 2 receptor status (ER/PR/HER2) in the breast tissue among Chinese pre- and post-menopausal women., Methods: Four thousand two hundred and eleven breast cancer patients were selected randomly from seven geographic regions of China from 1999 to 2008. Demographic data, risk factors, pathologic features, and biological receptor status of cases were collected from the medical charts. Chi-square test, fisher exact test, rank-correlation analysis, and multivariate logistic regression model were adopted to explore whether BMI differed according to biological receptor status in pre- and post-menopausal women., Results: Three thousand two hundred and eighty one eligible cases with BMI data were included. No statistically significant differences in demographic characteristics were found between the cases with BMI data and those without. In the rank-correlation analysis, the rates of PR+ and HER2+ were positively correlated with increasing BMI among post-menopausal women (rs BMI, PR+=0.867, P=0.001; rs BMI, HER2+ =0.636, P=0.048), but the ER+ rates did not vary by increasing BMI. Controlling for confounding factors, multivariate logistic regression models with BMI<24 kg/m(2) as the reference group were performed and found that BMI ≥ 24 kg/m(2) was only positively correlated with PR+ status among post-menopausal breast cancer cases (adjusted OR=1.420, 95% CI: 1.116-1.808, Wald=8.116, P=0.004)., Conclusions: Post-menopausal women with high BMI (≥ 24 kg/m(2)) have a higher proportion of PR+ breast cancer. In addition to effects mediated via the estrogen metabolism pathway, high BMI might increase the risk of breast cancer by other routes, which should be examined further in future etiological mechanism studies.

Long noncoding RNAs (lncRNAs) have crucial roles in cancer biology. We performed a genome-wide analysis of lncRNA expression in hepatoblastoma tissues to identify novel targets for further study of hepatoblastoma. Hepatoblastoma and normal liver tissue samples were obtained from hepatoblastoma patients. The genome-wide analysis of lncRNA expression in these tissues was performed using a 4×180 K lncRNA microarray and Sureprint G3 Human lncRNA Chips. Quantitative RT-PCR (qRT-PCR) was performed to confirm these results. The differential expressions of lncRNAs and mRNAs were identified through fold-change filtering. Gene Ontology (GO) and pathway analyses were performed using the standard enrichment computation method. Associations between lncRNAs and adjacent protein-coding genes were determined through complex transcriptional loci analysis. We found that 2736 lncRNAs were differentially expressed in hepatoblastoma tissues. Among these, 1757 lncRNAs were upregulated more than two-fold relative to normal tissues and 979 lncRNAs were downregulated. Moreover, in hepatoblastoma there were 420 matched lncRNA-mRNA pairs for 120 differentially expressed lncRNAs, and 167 differentially expressed mRNAs. The co-expression network analysis predicted 252 network nodes and 420 connections between 120 lncRNAs and 132 coding genes. Within this co-expression network, 369 pairs were positive, and 51 pairs were negative. Lastly, qRT-PCR data verified six upregulated and downregulated lncRNAs in hepatoblastoma, plus endothelial cell-specific molecule 1 (ESM1) mRNA. Our results demonstrated that expression of these aberrant lncRNAs could respond to hepatoblastoma development. Further study of these lncRNAs could provide useful insight into hepatoblastoma biology.

Aims: The goals of this paper were to evaluate the differentiation of bone marrow mesenchymal stem cells (BMSCs) into hepatocyte-like cells in vitro, and to determine whether stem cells can migrate and plant into the liver with portal hypertension accompanied by the end-stage of liver disease., Methods: BMSCs were isolated from rats and amplified with hepatocyte growth factor (HGF) and fibroblast growth factor-4 (FGF-4). The expression of alpha-fetoprotein (AFP), cytokeratin 18 (CK-18), and albumin (ALB) was detected by immunofluorescence in induced cells. Rats were randomly divided into experimental (with common bile duct ligation) and control groups. After injection of fluorescence labeled cells, cell distribution was observed under a fluorescence microscope. The integrated optical density (IOD) and cell distribution scores were evaluated using Image-Pro Plus 6.0 software. The portal pressure was measured before the rats were killed., Results: After being induced with HGF and FGF-4, the Golgi apparatus, endoplasmic reticulum, ribosomes, and mitochondria all significantly increased in the fifth generation cells. Immunofluorescent analysis showed that the induced cells expressed AFP, CK-18, and ALB. BMSCs were stained by CM-Dil, and the labeling rate was as high as 95.5%. The portal pressure in experimental group was much higher than that of the control group (18.04±2.35 vs. 9.75±1.40 cm H2O p<0.01). The IOD of transplanted cells in the experimental group was also significantly higher than that of the control group (11.30±2.09×10(5) vs. 2.93±0.88×10(5), p<0.01). In addition, the cell distribution score in the experimental group was lower than that of the control group (1.99±0.36 vs. 2.36±0.27, P<0.05)., Conclusions: The combination of HGF and FGF-4 induces the differentiation of BMSCs into hepatocyte-like cells, which express AFP, CK-18, and ALB. In addition, the recruitment of BMSCs (after transplantation in the spleen) was improved in rats with portal hypertension.

Introduction: Hormone receptors, human epidermal growth factor receptor 2 and some risk factors determine therapies and prognosis of breast cancer. The risk factors distributed differently between patients with receptors. This study aimed to investigate the distribution of risk factors between subtypes of breast cancer by the 3 receptors in Chinese native women with a large sample size., Methods: The multi-center study analyzed 4211 patient medical records from 1999 to 2008 in 7 regions of China. Data on patients' demographic information, risk factors (menopausal status, parity, body mass index) and receptor statuses were extracted. Breast cancer subtypes included ER (+/-), PR (+/-), HER2 (+/-), 4 ER/PR and 4 molecular subtypes. Wilcoxon and Chi-square tests were used to estimate the difference. The unconditional logistic regression model was used for analysis, and presented p-value after Bonferroni correction in the results., Results: Compared to patients with negative progesterone receptor, the positive patients were younger at diagnosis, and reported less likely in postmenopausal status and lower parity (p<0.05). Comparing with the subtype of ER+/PR+, ER+/PR- subtype were 4-year older at diagnosis (OR = 1.02), more likely to be postmenopausal (OR = 1.91) and more likely to have >1 parity (OR = 1.36) (p<0.05); ER-/PR- subtype were more likely to be postmenopausal (OR = 1.33) and have >1 parity (OR = 1.19) (p<0.05). In contrast to the luminal A subtype, triple negative subtype had a lower BMI (OR = 0.96) and ORs of overweight and obesity reduced by >20% (p<0.05)., Conclusion: In this study, it was found that Chinese female patients did have statistically significant differences of age, menopausal status, parity and body mass index between breast cancer subtypes. Studies are warranted to further investigate the risk factors between subtypes, which was meaningful for prevention and treatment among Chinese females.

Biliary atresia (BA) is a devastating cholestatic liver disease targeting infants. Current diagnosis depends on surgical exploration of the biliary tree. The aim of the present study was to identify potential biomarkers for the diagnosis of biliary atresia (BA). Two-dimensional electrophoresis was utilized for the identification of proteins that were differentially expressed in liver biopsies of 20 BA patients and 12 infants with non-BA neonatal cholestasis (NC) as controls. Using mass spectrometry, we identified 15 proteins with expressions significantly altered. Out of the 15 proteins identified, heat shock protein (HSP) 90 was the most significantly altered and was down-regulated in BA samples compared to NC samples using immunoblotting analysis. Our findings suggest that HSP90 might be a potential biomarker for the diagnosis of BA and may be used for monitoring further development and therapy for BA. This study demonstrated that a comprehensive strategy of proteomic identification combined with further validation should be adopted in biomarker discovery.