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51.
Mi Kyung Kwak Daniel T. Johnson Chunfang Zhu Suk Hyung Lee Ding-Wei Ye Richard Luong Zijie Sun 《PloS one》2013,8(1)
The PTEN tumor suppressor gene is frequently inactivated in human prostate cancer. Using Osr1 (odd skipped related 1)-Cre mice, we generated a novel conditional Pten knockout mouse strain, PtenLoxP:Osr1-Cre. Conditional biallelic and monoallelic Pten knockout mice were viable. Deletion of Pten expression was detected in the prostate of PtenLoxP/LoxP:Osr1-Cre mice as early as 2 weeks of age. Intriguingly, PtenLoxP/LoxP:Osr1-Cre mice develop high-grade prostatic intraepithelial neoplasms (PINs) with high penetrance as early as one-month of age, and locally invasive prostatic tumors after 12-months of age. PtenLoxP/+:Osr1-Cre mice show only mild oncogenic changes after 8-weeks of age. Castration of PtenLoxP/LoxP:Osr1-Cre mice shows no significant regression of prostate tumors, although a shift of androgen receptor (AR) staining from the nuclei to cytoplasm is observed in Pten null tumor cells of castrated mice. Enhanced Akt activity is observed in Pten null tumor cells of castrated PtenLoxP/LoxP:Osr1-Cre. This study provides a novel mouse model that can be used to investigate a primary role of Pten in initiating oncogenic transformation in the prostate and to examine other genetic and epigenetic changes that are required for tumor progression in the mouse prostate. 相似文献
52.
Huiyun Seo In-Seon Lee Jae Eun Park Sung Goo Park Do Hee Lee Byoung Chul Park Sayeon Cho 《PloS one》2013,8(11)
Protein tyrosine phosphatases play key roles in a diverse range of cellular processes such as differentiation, cell proliferation, apoptosis, immunological signaling, and cytoskeletal function. Protein tyrosine phosphatase non-receptor type 7 (PTPN7), a member of the phosphatase family, specifically inactivates mitogen-activated protein kinases (MAPKs). Here, we report that PTPN7 acts as a regulator of pro-inflammatory TNF-α production in RAW 264.7 cells that are stimulated with lipopolysaccharide (LPS) that acts as an endotoxin and elicits strong immune responses in animals. Stimulation of RAW 264.7 cells with LPS leads to a transient decrease in the levels of PTPN7 mRNA and protein. The overexpression of PTPN7 inhibits LPS-stimulated production of TNF-α. In addition, small interfering RNA (siRNA) analysis showed that knock-down of PTPN7 in RAW 264.7 cells increased TNF-α production. PTPN7 has a negative regulatory function to extracellular signal regulated kinase 1/2 (ERK1/2) and p38 that increase LPS-induced TNF-α production in macrophages. Thus, our data presents PTPN7 as a negative regulator of TNF-α expression and the inflammatory response in macrophages. 相似文献
53.
Myoung Jae Kang Kyoung Min Kim Jun Sang Bae Ho Sung Park Ho Lee Myoung Ja Chung Woo Sung Moon Dong Geun Lee Kyu Yun Jang 《Translational oncology》2013,6(3):282-289
BACKGROUND: Clear cell renal cell carcinoma (CRCC) is the most common malignant tumor of the kidney, and the clinical outcome of CRCC is related with the metastatic potential of CRCC. A significant proportion of metastatic CRCC remains incurable. Recently, immunotherapy against specific targets such as programmed death 1 (PD1) has been adapted for fatal cases of CRCC. MATERIALS AND METHODS: In this study, we aimed to evaluate the potential of tumor-infiltrating PD1-positive lymphocytes or FoxP3-positive regulatory T cells (Tregs) as predictors of the metastatic potential or prognosis of CRCC and investigate possible correlations with Epstein-Barr virus (EBV) infection in 199 cases of CRCC. RESULTS: PD1 positivity, high Treg number, and EBV infection all predicted poor overall survival (OS) by univariate analysis. PD1 positivity and high Treg numbers were also significantly correlated with more distant metastatic relapse (DMR) and poor relapse-free survival (RFS) by univariate analysis. PD1 positivity and high Treg number were independent prognostic indicators for OS. In addition, PD1 positivity was an independent predictor of RFS and DMR. EBV infection was an independent predictor of OS of CRCC. CONCLUSION: This study demonstrates that intratumoral infiltration of PD1-positive or FoxP3-positive lymphocytes can be used as significant prognostic indicators of CRCC and PD1 positivity could be very helpful in the prediction of latent distant metastasis of CRCCs. Therefore, evaluation of the infiltration of PD-positive cells or Tregs in CRCC may be useful diagnostic tools for the selection of patients who could benefit from PD1- or Treg-based immunotherapy. 相似文献
54.
Jung Ok Park Do‐Young Choi Dong‐Sic Choi Hee Joung Kim Jeong Won Kang Jae Hun Jung Jeong Hwa Lee Jayoung Kim Michael R. Freeman Kye Young Lee Yong Song Gho Kwang Pyo Kim 《Proteomics》2013,13(14):2125-2134
Microvesicles (MVs, also known as exosomes, ectosomes, microparticles) are released by various cancer cells, including lung, colorectal, and prostate carcinoma cells. MVs released from tumor cells and other sources accumulate in the circulation and in pleural effusion. Although recent studies have shown that MVs play multiple roles in tumor progression, the potential pathological roles of MV in pleural effusion, and their protein composition, are still unknown. In this study, we report the first global proteomic analysis of highly purified MVs derived from human nonsmall cell lung cancer (NSCLC) pleural effusion. Using nano‐LC–MS/MS following 1D SDS‐PAGE separation, we identified a total of 912 MV proteins with high confidence. Three independent experiments on three patients showed that MV proteins from PE were distinct from MV obtained from other malignancies. Bioinformatics analyses of the MS data identified pathologically relevant proteins and potential diagnostic makers for NSCLC, including lung‐enriched surface antigens and proteins related to epidermal growth factor receptor signaling. These findings provide new insight into the diverse functions of MVs in cancer progression and will aid in the development of novel diagnostic tools for NSCLC. 相似文献
55.
Yuwon Park Nam‐Soon Choi Sangjin Park Seung Hee Woo Soojin Sim Bo Yun Jang Seung M. Oh Soojin Park Jaephil Cho Kyu Tae Lee 《Liver Transplantation》2013,3(2):206-212
Remarkable improvements in the electrochemical performance of Si materials for Li‐ion batteries have been recently achieved, but the inherent volume change of Si still induces electrode expansion and external cell deformation. Here, the void structure in Si‐encapsulating hollow carbons is optimized in order to minimize the volume expansion of Si‐based anodes and improve electrochemical performance. When compared to chemical etching, the hollow structure is achieved via electroless etching is more advanced due to the improved electrical contact between carbon and Si. Despite the very thick electrodes (30 ~ 40 μm), this results in better cycle and rate performances including little capacity fading over 50 cycles and 1100 mA h g?1 at 2C rate. Also, an in situ dilatometer technique is used to perform a comprehensive study of electrode thickness change, and Si‐encapsulating hollow carbon mitigates the volume change of electrodes by adoption of void space, resulting in a small volume increase of 18% after full lithiation corresponding with a reversible capacity of about 2000 mA h g?1. 相似文献
56.
In-Gyun Lee Sun-Bok Jang Ji-Hun Kim Ki-Young Lee Kyu-Yeon Lee Hae-Kap Cheong Bong-Jin Lee 《Biomolecular NMR assignments》2013,7(2):159-162
Cell adhesion molecules play a crucial role in fundamental biological processes via regulating cell–cell interactions. Nerve injury induced protein1 (Ninjurin1) is a novel adhesion protein that has no significant homology with other known cell adhesion molecules. Here we present the assignment of an 81 aa construct for human Ninjurin1 Extracellular N-Terminal (ENT) domain, which comprises the critical adhesion domain. 相似文献
57.
Emmanuel S. Buys Yu-Chieh Ko Clemens Alt Sarah R. Hayton Alexander Jones Laurel T. Tainsh Ruiyi Ren Andrea Giani Maeva Clerté Emma Abernathy Robert E. T. Tainsh Dong-Jin Oh Rajeev Malhotra Pankaj Arora Nadine de Waard Binglan Yu Raphael Turcotte Daniel Nathan Marielle Scherrer-Crosbie Stephanie J. Loomis Jae H. Kang Charles P. Lin Haiyan Gong Douglas J. Rhee Peter Brouckaert Janey L. Wiggs Meredith S. Gregory Louis R. Pasquale Kenneth D. Bloch Bruce R. Ksander 《PloS one》2013,8(3)
Primary open angle glaucoma (POAG) is a leading cause of blindness worldwide. The molecular signaling involved in the pathogenesis of POAG remains unknown. Here, we report that mice lacking the α1 subunit of the nitric oxide receptor soluble guanylate cyclase represent a novel and translatable animal model of POAG, characterized by thinning of the retinal nerve fiber layer and loss of optic nerve axons in the context of an open iridocorneal angle. The optic neuropathy associated with soluble guanylate cyclase α1–deficiency was accompanied by modestly increased intraocular pressure and retinal vascular dysfunction. Moreover, data from a candidate gene association study suggests that a variant in the locus containing the genes encoding for the α1 and β1 subunits of soluble guanylate cyclase is associated with POAG in patients presenting with initial paracentral vision loss, a disease subtype thought to be associated with vascular dysregulation. These findings provide new insights into the pathogenesis and genetics of POAG and suggest new therapeutic strategies for POAG. 相似文献
58.
Dong Wook Han Natalia Tapia Marcos J. Araúzo-Bravo Kyung Tae Lim Kee Pyo Kim Kinarm Ko Hoon Taek Lee Hans R. Sch?ler 《PloS one》2013,8(6)
Epiblast stem cells (EpiSCs) and embryonic stem cells (ESCs) differ in their in vivo differentiation potential. While ESCs form teratomas and efficiently contribute to the development of chimeras, EpiSCs form teratomas but very rarely chimeras. In contrast to their differentiation potential, the reprogramming potential of EpiSCs has not yet been investigated. Here we demonstrate that the epiblast-derived pluripotent stem cells EpiSCs and P19 embryonal carcinoma cells (ECCs) exhibit a lower reprogramming potential than ESCs and F9 ECCs. In addition, we show that the low reprogramming ability is due to the lower levels of Sox2 in epiblast-derived stem cells. Consistent with this observation, overexpression of Sox2 enhances reprogramming efficiency. In summary, these findings suggest that a low reprogramming potential is a general feature of epiblast-derived stem cells and that the Sox2 level is a determinant of the cellular reprogramming potential. 相似文献
59.
Jung Hyun Yoon Kyung Hwa Han Eun-Kyung Kim Hee Jung Moon Min Jung Kim Young Joo Suh Ji Soo Choi Byeong-Woo Park 《PloS one》2013,8(2)
Introduction
To assess whether the value of CYFRA21-1 in the aspirates of ultrasonography-guided fine-needle aspiration biopsy (US-FNAB) can contribute to improving the performances of US-FNAB in the diagnosis of axillary lymph node (LN) metastasis in breast cancer patients.Methods
US-FNAB was performed in 156 axillary LNs in 152 breast cancer patients (mean age: 51.4 years, range: 17–92 years). Concentrations of CYFRA21-1 were measured from washouts of the syringe used during US-FNAB. Tumor marker concentrations, US-FNAB, intraoperative sentinel node biopsy (SNB), and surgical pathology results were reviewed and analyzed. For comparison, the values of CEA and CA15-3 were also measured from washouts.Results
Among the 156 LNs, 75 (48.1%) were benign, and 81 (51.9%) were metastases. Mean concentrations of CYFRA21-1 were significantly higher in metastasis compared to benign LNs (P<0.001). US-FNAB combined to CYFRA21-1 showed significantly higher sensitivity, NPV, and accuracy compared to US-FNAB alone (all values P<0.05). All diagnostic indices of US-FNAB combined to CYFRA21-1 were significantly higher compared to US-FNAB combined with CEA or CA15-3 (all P<0.001). Of the 28 metastatic LNs which showed metastasis on SNB, CYFRA21-1 showed higher positive rate of 75.0% (CEA or CA15-3∶60.7%, P = 0.076).Conclusion
Measuring CYFRA 21-1 concentrations from US-FNAB aspirates improves sensitivity, NPV, and accuracy of US-FNAB alone, and may contribute to reducing up to 75.0% of unnecessary intraoperative SNB. Compared to CEA or CA15-3, CYFRA21-1 shows significantly higher performances when combined to US-FNAB in the preoperative diagnosis of LN metastasis in breast cancer patients. 相似文献60.
Jae Young So Amanda K. Smolarek David M. Salerno Hubert Maehr Milan Uskokovic Fang Liu Nanjoo Suh 《PloS one》2013,8(1)