IKKß/NF-κB mediated the low doses of bisphenol A induced migration of cervical cancer cells.

Cervical cancer is considered as the second most common female malignant disease. There is an urgent need to illustrate risk factors which can trigger the motility of cervical cancer cells. Our present study revealed that nanomolar concentration of bisphenol A (BPA) significantly promoted the in vitro migration and invasion of cervical cancer HeLa, SiHa, and C-33A cells. Further, BPA treatment increased the expression of metalloproteinase-9 (MMP-9) and fibronectin (FN) in both HeLa and SiHa cells, while did not obviously change the expression of MMP-2, vimentin (Vim) or N-Cadherin (N-Cad). BAY 11-7082, the inhibitor of NF-κB, significantly abolished BPA induced up regulation of FN and MMP-9 in cervical cancer cells. While the inhibitors of PKA (H89), ERK1/2 (PD 98059), EGFR (AG1478), or PI3K/Akt (LY294002) had no effect on the expression of either FN or MMP-9. BPA treatment rapidly increased the phosphorylation of both IκBα and p65, stimulated nuclear translocation, and up regulated the promoter activities of NF-κB. The BPA induced up regulation of MMP-9 and FN and activation of NF-κB were mediated by phosphorylation of IKKß via PKC signals. Collectively, our study found for the first time that BPA stimulated the cervical cancer migration via IKK-ß/NF-κB signals.

Clinical Significance of First-Trimester Screening of the Retronasal Triangle for Identification of Primary Cleft Palate.

OBJECTIVE: To investigate the use of the retronasal triangle (RNT) for identification of orofacial cleft (OC) in the first trimester and the clinical application of three-dimensional (3D) ultrasound techniques for confirming the diagnosis of OC. METHODS: A total of 5,054 women with singleton pregnancies underwent first-trimester screening for Down syndrome at 11-13(+6) weeks. The RNT was scanned in each fetus, and 3D volumetric images of cases with abnormal or indeterminate RNT were obtained. RESULTS: Satisfactory images were obtained from all cases. Seven cases (1.4‰) of abnormal RNT were diagnosed as OC in the first trimester, which were confirmed at a 16 weeks scan or at a postmortem examination. One case that was considered a normal RNT was diagnosed with OC at 22(+2) weeks and after term delivery. Six cases of indeterminate RNT were diagnosed as normal by 3D ultrasound. Identification of OC by visualization of the RNT in the first trimester had a sensitivity of 87.5% and a specificity of 99.9%. CONCLUSION: The RNT is an important sonographic landmark that has a high sensitivity and specificity for the detection of OC in the first trimester. 3D ultrasound is an important tool that aids in confirming diagnosis of OC in the first and second trimesters.

Activation of G protein coupled estrogen receptor (GPER) promotes the migration of renal cell carcinoma via the PI3K/AKT/MMP-9 signals.

Renal cell carcinoma (RCC) is the third most frequent malignancy within urological oncology. However, the mechanisms responsible for RCC metastasis are still needed further illustration. Our present study revealed that a seven-transmembrane receptor G-protein coupled estrogen receptor (GPER) was highly detected in various RCC cell lines such as ACHN, OS-RC-2 and SW839. The activation of GPER by its specific agonist G-1 significantly promoted the in vitro migration and invasion of ACHN and OS-RC-2 cells. G-1 also up regulated the expression of matrix metalloproteinase-2 (MMP-2) and MMP-9. The inhibitor of MMP-9 (Cat-444278), but not MMP-2 (Sc-204092), abolished G-1 induced cell migration, which suggested that MMP-9 is the key molecule mediating G-1 induced RCC progression. Further, G-1 treatment resulted in phosphorylation of AKT and ERK in RCC cells. PI3K/AKT inhibitor (LY294002), while not ERK inhibitor (PD98059), significantly abolished G-1 induced up regulation of MMP-9 in both AHCN and OS-RC-2 cells. Generally, our data revealed that activation of GPER by its specific agonist G-1 promoted the metastasis of RCC cells through PI3K/AKT/MMP-9 signals, which might be a promising new target for drug discovery of RCC patients.

Analysis of feasibility of in vitro nuclear magnetic resonance tracking human umbilical cord mesenchymal stem cells by Gd-DTPA labeled.

OBJECTIVE: Three different kinds of transfection reagents were used to mediate the transfection of gadolinium-diethylenetriamine penta-acetic acid (Gd-DTPA) into human umbilical-cord-derived mesenchymal stem cells (hUCMSCs). The efficacy of different transfection reagents and the feasibility of NMR tracer in vitro of magnetized stem cells were estimated. METHODS: After purification by tissue explants adherent method, the biological characteristics of hUCMSCs in vitro were identified by subculture and amplification. Calcium phosphate, Effectene and liposome2000 were used to transfect Gd-DTPA-labeled hUCMSCs respectively, and cell counting was used to mediate the transfection of Gd-DTPA into hUCMSCs, which were then induced to lipoblast and osteoblast in vitro. The determination of the transfection activities of the transfection reagents was conducted by measuring the magnetic resonance imaging (MRI) signal intensity of the Gd-DTPA-labeled cells and the concentration of gadolinium ion in the cells. Furthermore, the relationship between the signal intensity of Gd-DTPA-labeled hUCMSCsMRI, cell subculture and generations was studied. RESULTS: Primary cells were obtained by tissue explants adherent for two weeks. The cells displayed a long spindle form and grew in swirl. After two passage generations, the cellular morphology became more homogeneous. The result detected by the flow cytometer showed that CD29C, D44, CD90, and CD105 were highly expressed, while no CD45, CD40, and HLA-DR expression was detected in the third generation cells. Directional induction in vitro caused the differentiation into lipoblast and osteoblast. After transfected by calcium phosphate, Effectene and liposome 2000, the signal intensity of stem cells was 2281.2±118.8, 2031.9±59.7 and 1887.4±40.8 measured by MRI. Differences between these three groups were statistically significant (P<0.05). The concentrations of gadolinium ion in three groups of stem cells were 0.178±0.009mg/L, 0.158±0.003mg/L and 0.120±0.002mg/L respectively, examined by inductively coupled plasma atomic emission spectrometry. No significant differences were found among these three groups (P<0.05). The proliferation and differentiation abilities of the Gd-DTPA-labeled stem cells were not affected. A minimum 5×10(4) Gd-DTPA-labeled stem cells could be traced with MRI in vitro and presented in high signal. The trace duration time in vitro was about 12days. CONCLUSIONS: Tissue explants adherent method can be availably applied to purify hUCMSCs. The Effectene method was proved to have the best transfection effect. The proliferation ability and differentiation potency of Gd-DTPA-labeled hUCMSCs were not affected, and the NMR of labeled stem cells in vitro was proved to be feasible.

XRCC1 polymorphisms are associated with cervical cancer risk and response to chemotherapy: a systematic review and meta-analysis.

BACKGROUND: Functional single nucleotide polymorphisms of x-ray repair cross-complementing protein 1 (XRCC1) have been suspected to contribute to uterine cervical cancer risk for a long time; however, most previous case-control studies were small sized and biased. Additionally, recent studies suggested that XRCC1 polymorphisms could be a biomarker of response to platinum-based chemotherapy. METHODS: A comprehensive search was conducted to retrieve eligible studies and odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated to measure association strength. RESULTS: A total of 13 studies were identified and analyzed. We found that the Arg194Trp polymorphism (Trp vs. Arg, OR=1.342, 95% CI: 1.176) was associated with increased risk of cervical cancer, while no significant association was found with Arg280His (His vs. Arg, OR=1.059, 95% CI: 0.863, 1.299) or Arg399Gln (Gln vs. Arg, OR=1.144, 95% CI: 0.938, 1.394). As for response to platinum- based chemotherapy, the variant XRCC1 399Gln allele (Gln vs. Arg, OR=0.345, 95% CI: 0.163, 0.729) was linked with a poor response; however, the Arg194Trp polymorphism (TrpArg vs. ArgArg, OR=6.421, 95% CI: 1.573, 26.205) predicted a good response. CONCLUSION: The Arg194Trp polymorphism of XRCC1 increases risk of cervical cancer; the variant 399Gln allele predicts poor response to platinum-based chemotherapy, while the Arg194Trp polymorphism indicates a good response.

Biliary cystadenocarcinoma diagnosed with real-time contrast-enhanced ultrasonography: report of a case with diagnostic features.

Biliary cystadenocarcinoma is a very rare malignant cystic tumor of the liver, which is often misdiagnosed due to a poor recognition of it. We report a case of a 60-year-old man with biliary cystadenocarcinoma with his real time contrast enhanced ultrasound (CEUS) characteristics compared to those of computed tomography (CT) and magnetic resonance imaging (MRI), which were correlated with the surgical and pathologic findings. Cystic wall enhancement, internal septations and intra-cystic solid portions in the arterial phase were observed on CEUS after contrast agent injection. The enhancement was washed out progressively and depicted as hypo-enhancement in the portal and late phases. CT revealed a large irregular cystic lesion in the left liver lobe with no clear septations and solid components. MRI showed an irregular cystic occupying lesion with septations.