Dysgerminoma in a case of 46, XY pure gonadal dysgenesis (swyer syndrome): a case report

Simple 46, XY gonadal dysgenesis syndrome, also called Swyer syndrome, is known as pure gonadal dysgenesis. Individuals with the syndrome are characterized by 46, XY karyotype and phenotypically female with female genital appearance, normal Müllerian structures and absent testicular tissue. The condition usually first becomes apparent in adolescence with delayed puberty and primary amenorrhea due to the gonads have no hormonal or reproductive potential. Herein, we report a case of dysgerminoma diagnosed in a dysgenetic gonad of a 21-year-old patient with Swyer syndrome

High Expression of DNMT1 was Correlated with beta-catenin Accumulation and Malignant Phynotype of Lung Squamous Cell Carcinoma and Adenocarcinoma

Background and objective DNA methyltransferase 1 (DNMT1) is one of the important molecules regulating DNA methylation. The abnormal expression of DNMT1 was associated with the methylation and inactivation of tumor suppressor gene and tumorigenesis. The aim of this study is to clarify the difference of DNMT1 expression between lung cancer tissues and corresponding normal lung tissues, to analyze the relationships between DNMT1 expression and clinicopathologic characteristics of lung squamous cell carcinoma and adenocarcinoma, and to investigate the correlation between the expressions of DNMT1 and β-catenin. Methods The expressions of DNMT1 and β-catenin were examined in 84 lung squamous cell carcinoma and adenocarcinoma tissues and corresponding normal lung tissues using tissue microarray and immunohistochemistry. Results The average positive rate of DNMT1 was significantly higher in 84 lung cancer tissues [(58.04±35.07)%] than that in corresponding normal lung tissues [(6.88±10.26)%](t=12.835, P < 0.001). The high expression of DNMT1 was positively correlated with adenocarcinoma histological type (r=0.365, P=0.001), poor differentiation (r=0.253, P=0.021) and lymph node metastasis (r=0.246, P=0.024) in lung cancer. The expression of DNMT1 was significantly correlated with the cytoplasmic expression of β-catenin (r=0.571, P < 0.001). Conclusion The high expression of DNMT1 was a common phenomenon in lung squamous cell carcinoma and adenocarcinoma. The high expression of DNMT1 was correlated with the malignant phynotype of lung cancer. DNMT1 may express coordinately with β-catenin in lung cancer

Bufalin Induces Mitochondria-Dependent Apoptosis in Pancreatic and Oral Cancer Cells by Downregulating hTERT Expression via Activation of the JNK/p38 Pathway

Bufalin, a digoxin-like active component of the traditional Chinese medicine Chan Su, exhibits potent antitumor activities in many human cancers. Bufalin induces mitochondria-dependent apoptosis in cancer cells, but the detailed molecular mechanisms are largely unknown. hTERT, the catalytic subunit of telomerase, protects against mitochondrial damage by binding to mitochondrial DNA and reducing mitochondrial ROS production. In the present study, we investigated the effects of bufalin on the cell viability, ROS production, DNA damage, and apoptosis of CAPAN-2 human pancreatic and CAL-27 human oral cancer cells. Bufalin reduced CAPAN-2 and CAL-27 cell viability with IC50 values of 159.2 nM and 122.6 nM, respectively. The reduced cell viability was accompanied by increased ROS production, DNA damage, and apoptosis and decreased expression of hTERT. hTERT silencing in CAPAN-2 and CAL-27 cells by siRNA resulted in increased caspase-9/-3 cleavage and DNA damage and decreased cell viability. Collectively, these data suggest that bufalin downregulates hTERT to induce mitochondria-dependent apoptosis in CAPAN-2 and CAL-27 cells. Moreover, bufalin increased the phosphorylation of JNK and p38-MAPK in CAPAN-2 and CAL-27 cells, and blocking the JNK/p38-MAPK pathway using the JNK inhibitor SP600125 or the p38-MAPK inhibitor SB203580 reversed bufalin-induced hTERT downregulation. Thus, the JNK/p38 pathway is involved in bufalin-induced hTERT downregulation and subsequent induction of apoptosis by the mitochondrial pathway

P120-Catenin Isoforms 1 and 3 Regulate Proliferation and Cell Cycle of Lung Cancer Cells via β-Catenin and Kaiso Respectively

<div><h3>Background</h3><p>The different mechanisms involved in p120-catenin (p120ctn) isoforms' 1/3 regulation of cell cycle progression are still not elucidated to date.</p> <h3>Methods and Findings</h3><p>We found that both cyclin D1 and cyclin E could be effectively restored by restitution of p120ctn-1A or p120ctn-3A in p120ctn depleted lung cancer cells. When the expression of cyclin D1 was blocked by co-transfection with siRNA-cyclin D1 in p120ctn depleted cells restoring p120ctn-1A or 3A, the expression of cyclin E was slightly decreased, not increased, implying that p120ctn isoforms 1 and 3 cannot up-regulate cyclin E directly but may do so through up-regulation of cyclin D1. Interestingly, overexpression of p120ctn-1A increased β-catenin and cyclin D1 expression, while co-transfection with siRNA targeting β-catenin abolishes the effect of p120ctn-1A on up-regulation of cyclin D1, suggesting a role of β-catenin in mediating p120ctn-1A's regulatory function on cyclin D1 expression. On the other hand, overexpression of p120ctn isoform 3A reduced nuclear Kaiso localization, thus decreasing the binding of Kaiso to KBS on the cyclin D1 promoter and thereby enhancing the expression of cyclin D1 gene by relieving the repressor effect of Kaiso. Because overexpressing NLS-p120ctn-3A (p120ctn-3A nuclear target localization plasmids) or inhibiting nuclear export of p120ctn-3 by Leptomycin B (LMB) caused translocation of Kaiso to the nucleus, it is plausible that the nuclear export of Kaiso is p120ctn-3-dependent.</p> <h3>Conclusions</h3><p>Our results suggest that p120ctn isoforms 1 and 3 up-regulate cyclin D1, and thereby cyclin E, resulting in the promotion of cell proliferation and cell cycle progression in lung cancer cells probably via different protein mediators, namely, β-catenin for isoform 1 and Kaiso, a negative transcriptional factor of cyclin D1, for isoform 3.</p> </div

The Role of Tc-99m DTPA Renal Dynamic Scintigraphy in Retroperitoneal Liposarcoma

Purpose. Technetium-99m diethylene triamine pentaacetic acid (Tc-99m DTPA) renal dynamic scintigraphy is a widely used imaging technique that evaluates renal function of patients with extrarenal abnormalities, but its clinical value in potentially offering us information on proliferation of liposarcoma has not yet been reported. Methods. We retrospectively reviewed 7 patients with histopathologically confirmed retroperitoneal liposarcoma who underwent Tc-99m DTPA renal dynamic scintigraphy. The clinical data, histopathological findings, Glomerular Filtration Rate (GFR), and Tc-99m DTPA uptake were recorded. Results. Dedifferentiated liposarcoma and well-differentiated liposarcoma showed dissimilar degrees of Tc-99m DTPA uptake, an observation that correlated with Ki-67 expression (p<0.01). 4 of the 7 patients were diagnosed with dedifferentiated liposarcoma, showing a moderate uptake of Tc-99m DTPA and greater than 20% Ki-67 expression on histological slides. Meanwhile, the remaining 3 patients, diagnosed with well-differentiated liposarcoma, showed no uptake of Tc-99m DTPA and Ki-67 expression of less than 5%. Conclusions. This study suggests that Tc-99m DTPA renal dynamic scintigraphy provides diagnostic value in patients with retroperitoneal liposarcoma, not only in evaluating renal function but also in visualizing lesion-related radionuclide uptake, which may potentially offer further clinical insights into tumor proliferation and provide prognostic value for clinical outcomes in patients with retroperitoneal liposarcoma

MiR-3646 accelerates inflammatory response of Ang II-induced hVSMCs via CYP2J2/EETs axis in hypertension model

Background Inflammatory response of human vascular smooth muscle cells (hVSMCs) is a driving factor in hypertension progression. It has been reported that miR-3646 was significantly up-regulated in serum samples from patients with coronary artery disease and acute myocardial infarction mice. However, its role and underlying molecular mechanism related to inflammatory response of angiotensin II (Ang II)-induced hVSMCs remain unclear. Objective We aimed to explore the potential molecular mechanisms related to inflammatory response of angiotensin II (Ang II)-induced hVSMCs. Methods Ang II–induced hypertension model was established after hVSMCs treated with 1 μM Ang II at 24 h. The interaction between microRNA 3646 (miR-3646) and cytochrome P450 2J2 (CYP2J2) was assessed by dual-luciferase reporter gene assay. MTS assay, Lipid Peroxidation MDA Assay Kit, ELISA, Western blot, and qRT-PCR were performed to examine viability, malondialdehyde (MDA) level, inflammatory cytokine levels, and the level of genes and proteins. Results Our findings illustrated that miR-3646 was up-regulated but CYP2J2 was down-regulated in Ang II–induced hVSMCs. Mechanically, miR-3646 negatively targeted to CYP2J2 in Ang II–induced hVSMCs. These findings indicated that miR-3646 regulated inflammatory response of Ang II–induced hVSMCs via targeting CYP2J2. Moreover, functional researches showed that CYP2J2 overexpression alleviated inflammatory response of Ang II–induced hVSMCs via epoxyeicosatrienoic acids/peroxisome proliferator-activated receptor-γ (EETs/PPARγ) axis, and miR-3646 aggravated inflammatory response of Ang II–induced hVSMCs via mediating CYP2J2/EETs axis. Conclusion MiR-3646 accelerated inflammatory response of Ang II–induced hVSMCs via CYP2J2/EETs axis. Our findings illustrated the specific molecular mechanism of miR-3646 regulating hypertension

p120ctn-3 inhibit Kaiso from binding to cyclin D1 promoter by regulating the nuclear/cytoplasmic shuttle of Kaiso.

<p>(<b>A</b>) Transfection of p120ctn-3A in A549 cells significantly increased Kaiso in the cytoplasm (CYTO, *, p = 0.000) and reduced Kaiso in the nucleus (NE, *, p = 0.000). However, no significant difference of subcellular localization of Kaiso was found between p120ctn-1A overexpression cells and control cells (CYTO, **, p = 0.135, NE, **, p = 0.774). These results suggest that a high level of p120ctn-3A may be able to promote the nuclear export of Kaiso, but p120ctn-1A does not appear to have this function. Incubating cells transfected with p120ctn-3A with LMB or transfecting NLS-p120ctn-3A in A549 cells increased nuclear p120ctn-3A (*, p = 0.000, or +, p = 0.000) and nuclear Kaiso (NE, +, p = 0.000 or ++, p<0.001), but reduced cytoplasmic Kaiso (CYTO, +, p = 0.000 or ++, p = 0.002) compared to the cells with only overexpressed p120ctn-3A, implying that the nuclear export of Kaiso is likely to be p120ctn-3-dependent. (<b>B</b>) p120ctn-1A overexpression did not change the binding of Kaiso to KBS on the cyclin D1 promoter, whereas p120ctn-3A overexpression significantly reduced the binding of Kaiso to KBS on the cyclin D1 promoter.</p