bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of wnts in prostate cancer bone metastases
Authors: Hall Christopher L. , Kang Sona , MacDougald Ormond A. , Keller Evan T. 
Published: January 2006

AbstractProstate cancer (CaP) is unique among all cancers in that when it metastasizes to bone, it typically forms osteoblastic lesions (characterized by increased bone production). CaP cells produce many factors, including Wnts that are implicated in tumor‐induced osteoblastic activity. In this prospectus, we describe our research on Wnt and the CaP bone phenotype. Wnts are cysteine‐rich glycoproteins that mediate bone development in the embryo and promote bone production in the adult. Wnts have been shown to have autocrine tumor effects, such as enhancing proliferation and protecting against apoptosis. In addition, we have recently identified that CaP‐produced Wnts act in a paracrine fashion to induce osteoblastic activity in CaP bone metastases. In addition to Wnts, CaP cells express the soluble Wnt inhibitor dickkopf‐1 (DKK‐1). It appears that DKK‐1 production occurs early in the development of skeletal metastases, which results in masking of osteogenic Wnts, thus favoring osteolysis at the metastatic site. As metastases progress, DKK‐1 expression decreases allowing for unmasking of Wnt's osteoblastic activity and ultimately resulting in osteosclerosis at the metastatic site. We believe that DKK‐1 is one of the switches that transitions the CaP bone metastasis activity from osteolytic to osteoblastic. Wnt/DKK‐1 activity fits a model of CaP‐induced bone remodeling occurring in a continuum composed of an osteolytic phase, mediated by receptor activator of NFkB ligand (RANKL), parathyroid hormone‐related protein (PTHRP) and DKK‐1; a transitional phase, where environmental alterations promote expression of osteoblastic factors (Wnts) and decreases osteolytic factors (i.e., DKK‐1); and an osteoblastic phase, in which tumor growth‐associated hypoxia results in production of vascular endothelial growth factor and endothelin‐1, which have osteoblastic activity. This model suggests that targeting both osteolytic activity and osteoblastic activity will provide efficacy for therapy of CaP bone metastases. J. Cell. Biochem. 97: 661–672, 2006. © 2005 Wiley‐Liss, Inc.
Chromatin remodeling in DNA replication
Authors: Falbo Karina B. , Shen Xuetong 
Published: January 2006

AbstractChromatin remodeling complexes have evolved to solve a very basic problem for eukaryotic cells accomodation of the genome to fit the dimensions of the nucleus without loss of access to the DNA molecule. In the nucleus, DNA is wrapped around histones to form nucleosomes and other higher order compact chromatin structures. Chromatin remodeling complexes enable highly regulated access to DNA sequences in the context of chromatin, and it is well known that these complexes are involved in regulation of transcription. However, gene expression is not the only process that occurs in the nucleus. DNA has to be replicated, recombined, and repaired. In this regard, it is notable that the recent discoveries have linked ATP‐dependent remodeling complexes to DNA damage repair. These results have raised challenging questions about the possible versatility of chromatin remodeling complexes in other nuclear activities, particularly in DNA replication, since a number of recent studies have suggested a connection between this essential cellular process and chromatin remodeling. However, the chromatin remodeling events regulating DNA replication have not been extensively investigated. The aim of this prospect is to summarize recent studies that implicate chromatin remodeling in DNA replication and to address potential roles of chromatin remodeling at various stages of eukaryotic DNA replication. J. Cell. Biochem. 97: 684–689, 2006. © 2005 Wiley‐Liss, Inc.
Rad9, an evolutionarily conserved gene with multiple functions for preserving genomic Integrity
Authors: Lieberman Howard B. 
Published: January 2006

AbstractThe Rad9 gene is evolutionarily conserved. Analysis of the gene from yeast, mouse and human reveal roles in multiple, fundamental biological processes primarily but not exclusively important for regulating genomic integrity. The encoded mammalian proteins participate in promoting resistance to DNA damage, cell cycle checkpoint control, DNA repair, and apoptosis. Other functions include a role in embryogenesis, the transactivation of multiple target genes, co‐repression of androgen‐induced transcription activity of the androgen receptor, a 3′‐5′ exonuclease activity, and the regulation of ribonucleotide synthesis. Analyses of the functions of Rad9, and in particular its role in regulating and coordinating numerous fundamental biological activities, should not only provide information about the molecular mechanisms of several individual cellular processes, but might also lend insight into the more global control and coordination of what at least superficially present as independent pathways. J. Cell. Biochem. 97: 690–697, 2006. © 2005 Wiley‐Liss, Inc.
A computational study of the lowest singlet and triplet states of neutral and dianionic 1,2‐substituted icosahedral and octahedral o‐carboranes
Authors: Oliva Josep M. , Serrano–Andrés Luis 
Published: January 2006

AbstractThis work introduces a calibrated B3LYP/6‐31G(d) study on the electronic structure of singlet and triplet neutral species of 1,2‐substituted icosahedral 1,2‐R2‐1,2‐C2B10H10 and octahedral 1,2‐R2‐1,2‐C2B4H4 molecules with R = {H, OH, SH, NH2, PH2, CH3, SiH3} and their respective dianions formed by proton removal on each R group. A variety of small adiabatic singlet‐triplet gaps ΔEST are obtained from these systems ranging from 2.93 eV (R = NH2) ≤ ΔEST ≤ 3.98 eV (R = SiH3) for the icosahedral neutrals and 1.56 eV (R = NH2) ≤ ΔEST ≤ 4.13 eV (R = SiH3) for the octahedral neutrals, these gaps being globally smaller for the dianionic systems, ranging from 0.94 eV (R− = CH2−) ≤ ΔEST ≤ 2.01 (R− = e−) for the icosahedral dianions 1,2‐(R−)2‐C2B10H10 and 0.91 (R− = CH2−) ≤ ΔEST ≤ 2.41 (R = SiH2−) for the octahedral dianions 1,2‐(R−)2C2B4H4 (R− = e−, O−, S−, NH−, PH−, CH2−, PH2−). The different gaps lie within or in the neighborhood of the visible region of the electromagetic spectrum. The optimized geometries for the molecular cage remain similar in substituted icosahedral and octahedral singlet states, while a rich variety of different structures can be found for the optimized triplet states. © 2006 Wiley Periodicals, Inc. J Comput Chem 27: 524–535, 2006
Immunohistochemical evaluation of pRb2/p130, VEGF, EZH2, p53, p16, p21waf‐1, p27, and PCNA in Barrett's esophagus
Authors: Merola Elettra , Mattioli Eliseo , Minimo Corrado , Zuo Weineng , Rabitti Carla , Cicala Michele , Caviglia Renato , Pollice Lucio , Gabbrielli Armando , Giordano Antonio , Claudio Pier Paolo 
Published: January 2006

AbstractControl of the G1/S‐phase transition as well as angiogenic switch are two of the most studied mechanisms in cancer. The current study examined the correlation between the immunohistochemical expression of pRb2/p130, VEGF, EZH2, p53, p16, p21waf‐1, p27, and PCNA in Barrett's esophagus (BE). Overall, p53 showed a much higher expression in BE patients (up to 50%) than in controls (1–10%) (P < 0.005). Also p21 showed a downregulation in BE when compared to normal esophagus (70% of cells vs. 65%), but the difference did not show any statistical significance (P = 0.45). pRb2/p130 was detected in 80% of cells in normal controls, but showed positive in only 20% of cells in BE biopsies. Additionally, Rb2/p130 expression was inversely correlated to that of VEGF, EZH2, and PCNA (P < 0.0001, P = 0.0032, P < 0.001, respectively). p27 stained more intensely and in a widespread manner (70%) cells in normal esophageal tissues but about only 30% in BE samples (P < 0.001). Lastly, in accordance with other reports, we also found p16 expressed by immunohistochemistry at high levels in normal controls and at low levels in BE (P < 0.001). In conclusion, p16, p21, p27, and p53 staining confirmed previously published data. Interestingly, pRb2/p130 expression was found significantly decreased in metaplastic epithelium compared to normal controls and showed significant inverse correlation with the expression of other markers, such as VEGF, EZH2, and PCNA. These data, taken together, indicate that these molecular events occurring in Barrett's metaplasia (BM) may represent one of the many steps taking place during esophageal malignant progression such as impairment of cell‐cycle control, altered differentiation, and unbalanced angiogenesis. J. Cell. Physiol. 207: 512–519, 2006. © 2006 Wiley‐Liss, Inc.
Regulation of Ang2 release by PTEN/PI3‐kinase/Akt in lung microvascular endothelial cells
Authors: Tsigkos Stelios , Zhou Zongmin , Kotanidou Anastasia , Fulton David , Zakynthinos Spyros , Roussos Charis , Papapetropoulos Andreas 
Published: January 2006

AbstractAngiopoietin‐2 (Ang2) is a Tie‐2 ligand that destabilizes vascular structures, allowing for neovascularization or vessel regression depending on local vascular endothelial cell growth factor (VEGF) concentrations. Although various stimuli have been shown to affect Ang2 expression, information on the underlying mechanisms involved in Ang2 production in endothelial cells (EC) is just beginning to emerge. In the present study, we have used adenovirus‐mediated gene transfer and pharmacological inhibitors to examine the role of the PTEN/PI3‐K/Akt pathway on Ang2 release. Inhibition of PI3‐kinase with wortmannin led to a stimulation of basal Ang2 release in EC, while overexpression of an active form of Akt reduced Ang2. In addition, adenovirus‐mediated gene transfer of the phosphatase PTEN stimulated Ang2 release. Incubation of the cells with Ang1, an agent that activates the PI3‐K/Akt pathway in EC, reduced Ang2 release. This effect of Ang1 could be prevented by wortmannin and LY‐294002 pretreatment. Similarly, in VEGF‐treated EC the increase in Ang2 production observed was greater in the presence of a PI3‐K inhibitor. Our observations that PTEN acts as a positive modulator of Ang2 release, while activation of the PI3‐K/Akt pathway downregulates Ang2, reveal an additional mechanism through which the PTEN/PI3‐K/Akt pathway could affect the angiogenic process. J. Cell. Physiol. 207: 506–511, 2006. © 2006 Wiley‐Liss, Inc.
Bone morphogenetic protein 4 mediates bile duct ligation induced liver fibrosis through activation of Smad1 and ERK1/2 in rat hepatic stellate cells
Authors: Fan Jianghong , Shen Hong , Sun Yu , Li Ping , Burczynski Frank , Namaka Mike , Gong Yuewen 
Published: January 2006

AbstractBone morphogenetic proteins (BMPs) are the important cytokine involving in cell differentiation especially in bone morphogenesis. Hepatic stellate cells (HSCs) undergo a trans‐differentiation during their activation after liver injury. Although it has been demonstrated that BMP2 and BMP4 significantly increased the abundance of smooth muscle alpha actin (α‐SMA) in cultured HSCs, the expression of BMPs has not been examined during the activation of HSCs. In current study, we documented the expression of BMP4 in bile duct ligation (BDL) rats and HSCs in culture. We have found that the expression of BMP4 was significantly elevated in the liver of BDL rats. The increase in BMP4 protein showed two peaks during 6 weeks after BDL. The expression and phosphorylation of Smad1, ERK1/2 and p38 were also elevated after BDL. Moreover, there was a gradual elevation of BMP4 mRNA abundance during 24 days' in vitro culture of HSCs. Furthermore, BMP4 stimulated phosphorylation of Smad1 and ERK1/2 in HSCs. In conclusion, BMP4 expression was significantly increased in the liver of BDL rats and HSCs in culture. These findings indicate that BMP4 may mediate HSC activation through activation of Smad1 and ERK1/2. J. Cell. Physiol. 207: 499–505, 2006. © 2006 Wiley‐Liss, Inc.
Assembly of nuclear matrix–bound protein complexes involved in non‐homologous end joining is induced by inhibition of DNA topoisomerase II
Authors: Kantidze Omar L. , Iarovaia Olga V. , Razin Sergey V. 
Published: January 2006

AbstractTopoisomerases maintain the DNA structure by relieving the torsional stress and alleviating other topological problems occurring in DNA during transcription and replication. Topoisomerase II appears to have a close association with the family of proteins involved in the organization of chromatin in a series of loops on the proteinaceous chromosomal matrix. Beyond its physiological functions, topoisomerase II is the target for some of the most active anticancer drugs. Inhibition of the topoisomerase II function can result in DNA double‐strand breaks (DSBs) and, thus, lead to chromosomal translocations. The earliest event during DSB repair is phosphorylation of histone H2AX at S139 (so‐called γH2AX) which is believed to serve as a focal point for the assembly of repair proteins at the DSB. In this work, we have demonstrated the formation of γH2AX foci in two human cell lines ‐ K562 and HeLa ‐ after suppression of topoisomerase II activity with etoposide. Furthermore, these foci remained visible at nuclear matrices and colocalized with the major components of non‐homologous end joining (NHEJ) system of DSBs repair. Thus, inhibition of topoisomerase II activity triggers assembly of NHEJ complexes at the nuclear matrix. J. Cell. Physiol. © 2006 Wiley‐Liss, Inc.
Dynamic regulation and involvement of the heat shock transcriptional response in arsenic carcinogenesis
Authors: Khalil Sara , Luciano Jason , Chen Wenjun , Liu Alice Y.‐C. 
Published: January 2006

AbstractThe objective of this study is to better define induction of the heat shock response by arsenite, and to evaluation if induction of heat shock proteins (HSPs) contributes to the carcinogenic activity of arsenite. We show here that arsenite is a ubiquitous inducer of the heat shock response in mammalian cells: that it activated heat shock transcription factor 1 (HSF1) DNA‐binding activity, enhanced hsp 70 promoter, and induced hsp70mRNA and synthesis of HSP chaperones. Using a high throughput hsp70 promoter‐luciferase reporter assay, we observed a hormetic dose response where low concentrations of arsenite stimulated and high concentrations inhibited. Further, the response was time‐dependent such that with longer times of incubation, the dose response shifted to the left. The effect of arsenite in inducing the hsp 70‐luciferase reporter absolutely required a functional HSF1 as it was not observed in HSF1 minus cells but re‐instated by expression of HSF1. Consistent with the suggestion that arsenic targets vicinal cysteine‐SH, we showed that dithiothreitol blocked the effect of arsenite. Assays of cell viability and caspase showed that arsenite caused a dose‐dependent increase in cell death by activation of caspase 3/7 and pre‐induction of HSPs blunted these effects. Using anchorage independent cell growth as a late stage tumor promotion assay, we showed that low concentrations of arsenite had a growth promoting effect, which was enhanced by moderate heat shock. Our study provides evidence that induction of the heat shock response is a sensitive biomarker of arsenic exposure and that induction of HSPs likely contributes to the tumor promotion effect of arsenic. J. Cell. Physiol. 207: 562–569, 2006. © 2006 Wiley‐Liss, Inc.
Analysis of dystroglycan regulation and functions in mouse mammary epithelial cells and implications for mammary tumorigenesis
Authors: Sgambato A. , Di Salvatore M.A. , De Paola B. , Rettino A. , Faraglia B. , Boninsegna A. , Graziani C. , Camerini A. , Proietti G. , Cittadini A. 
Published: January 2006

AbstractAbnormalities in the interactions of cells with the extracellular matrix (ECM) play an important role in the development and progression of many types of cancer and are a hallmark of malignant transformation. The dystroglycan (DG) complex is a transmembrane glycoprotein that forms a continuous link from the ECM to the actin cytoskeleton, providing structural integrity and perhaps transducing signal, in a manner similar to integrins. Deregulated expression of DG has been reported in a variety of human malignancies and related to tumor differentiation and aggressiveness. In breast cancer, reduced DG expression has been associated with patient survival and with loss of differentiation of tumor cells. Limited data are available on DG physiology in epithelial cells. In this study, we used the HC11 spontaneously immortalized murine mammary epithelial cells to study DG function(s) and regulation in normal cells. We found that expression of DG protein and mRNA is cell‐cycle and cell‐density regulated in these cells. Moreover, expression of both DG subunits increased upon lactogenic differentiation of the HC11 cells. The turnover of cell‐surface‐expressed DG was evaluated in the same cells and half‐life of DG subunits was evaluated to be about 12 h. DG‐specific small inhibitory RNAs were used to analyze the effects of a reduced expression of DG in these cells. Cells in which DG expression was suppressed were growth inhibited, accumulated in the S‐phase of the cell cycle, failed to undergo lactogenic differentiation, and displayed an increase in the percentage of apoptotic cells. Moreover, changes were observed in the expression and/or activity of several molecules involved in cell growth control. These results demonstrate that DG expression is tightly regulated in normal mammary epithelial cells and support the hypothesis that DG is involved in several functions other than structural integrity in these cells. This finding provides new insight into the roles played by DG in epithelial cell physiology and will contribute to our understanding of its involvement in the process of epithelial cell transformation. J. Cell. Physiol. 207: 520–529, 2006. © 2006 Wiley‐Liss, Inc.
ERK1/2 and p38 MAP kinase control MMP‐2, MT1‐MMP, and TIMP action and affect cell migration: A comparison between mesothelioma and mesothelial cells
Authors: Zhong Jun , Cornelsen Gencay Mikael M. , Bubendorf Lukas , Burgess Janette K. , Parson Holly , Robinson Bruce W.S. , Tamm Michael , Black Judith L. , Roth Michael 
Published: January 2006

AbstractPleural malignant mesothelioma is a locally aggressive tumor of mesothelial cell origin. In other tumor types high expression of matrix metalloproteinase (MMP)‐2, together with membrane‐type1‐MMP (MT1‐MMP), and low levels of the tissue inhibitor of MMP (TIMP)‐2 have been correlated with aggressive tumor progression and low survival rates. Therefore, we compared the expression and activation of these three factors and their regulation by two mesothelioma associated growth factors, platelet‐derived growth factor (PDGF)‐BB, and transforming growth factor (TGF)‐β1 in six human mesothelioma and one mesothelial cell line. Polymerase chain reaction (PCR), immnuoblotting, zymography, and small inhibitory RNAs (siRNA) were used to study gene expression, protein activation, and signal transduction. To proof the relevance of our in vitro data immunohistochemistry was performed in tissue sections. PDGF‐BB induced, while TGF‐β1 inhibited cell proliferation. PDGF‐BB was a chemoattractant for mesothelial cells, and its effect was increased in the presence of TGF‐β1. TGF‐β1 stimulated the de novo synthesis of pro‐MMP‐2 in both cell types. Pro‐MMP‐2 synthesis involved p38 MAP kinase. In cell culture and tissue sections only mesothelial cells expressed MT1‐MMP. Migration of mesothelioma cells was dependent on the presence of MT1‐MMP. Migration, but not proliferation of mesothelioma cells was inhibited by oleoyl‐N‐hydroxylamide, TIMP‐2, and siRNA for MT1‐MMP. Our data suggest that in mesothelioma cells the phosphorylation of p38 MAP kinase is deregulated and is involved in pro‐MMP‐2 expression. Mesothelioma progression depends on an interaction with mesothelial cells that provide MT1‐MMP necessary to activate pro‐MMP‐2 to facilitate migration through an extracellular matrix (ECM) layer. J. Cell. Physiol. 207: 540–552, 2006. © 2006 Wiley‐Liss, Inc.
Proteolytic activation of latent TGF‐β precedes caspase‐3 activation and enhances apoptotic death of lung epithelial cells
Authors: Solovyan Victor T. , Keski‐Oja Jorma 
Published: January 2006

AbstractTransforming growth factors β (TGF‐βs) are multifunctional cytokines, which are secreted in latent forms in large latent TGF‐β complexes (LL‐TGF‐β) with subsequent deposition to the extracellular matrix (ECM). While a variety of mechanisms capable of activating latent TGF‐β in vitro have been described, the physiological conditions, which promote the activation of TGF‐β in vivo are poorly understood. Mink lung epithelial cells (Mv1Lu) are a widely used model for evaluation of the effects of exogenous TGF‐β both in transcriptional and growth inhibitor assays. We find here that apoptosis of Mv1Lu cells, induced either by staurosporine or serum deprivation, is accompanied by proteolytic processing of LL‐TGF‐β and the activation of endogenous TGF‐β. Activation of TGF‐β preceded caspase‐3 activation and was almost completely suppressed by the serine protease inhibitor, AEBSF. Both exogenous and endogenously activated TGF‐βs were able to enhance the apoptotic response of Mv1Lu cells leading to potentiation of cell death. Potentiation of cell death by activated TGF‐β was associated with downregulation of Akt and p38 MAPK, which were both activated at the initial stages of Mv1Lu apoptosis and were suppressed by exogenous TGF‐β. Pharmacological interruption of either phosphoinositide‐3‐kinase (PI‐3K)/Akt or p38 MAPK signaling by the specific inhibitors mimicked the effect of TGF‐β leading to potentiation of cell death. Current results suggest that proteolytic activation of endogenous TGF‐β is a component of the apoptotic response, capable of modulating the death of Mv1Lu cells by inhibition of both PI‐3K/Akt and p38 MAPK‐dependent survival pathways. J. Cell. Physiol. 207: 445–453, 2006. © 2006 Wiley‐Liss, Inc.
Non‐freezing points below zero induce low‐temperature breakdown of kiwifruit at harvest
Authors: Gerasopoulos Dimitrios , Chlioumis George , Sfakiotakis Evangelos 
Published: January 2006

AbstractTo induce low‐temperature breakdown (LTB) at harvest, a post‐storage disorder of kiwifruit, kiwifruit were exposed to −2 °C (a temperature determined to be above the freezing point), for 0 (control), 6, 12, 18, 24, 30, 36 and 42 h, followed by 5 days at 20 °C. Kiwifruit were also stored at −0.5 °C for 16 and 24 weeks plus 5 days at 20 °C. LTB incidence and severity were measured on the cut surfaces following slicing at the upper, middle and lower parts of each fruit subjected to −2 °C, whereas in stored fruit LTB incidence was measured following slicing at the middle part. Electrolyte leakage (ELL) was also determined. Exposure of fruit to −2 °C resulted in induction of LTB incidence and severity, which increased with the duration of exposure, particularly, on the upper fruit part. Maximum ELL during exposure at −2 °C for 36 h or during storage at −0.5 °C for 16 weeks was as high as 50% of that of the frozen fruit. Fruit exposed to −2 °C or stored at −0.5 °C had similar LTB symptoms but both differed from those observed in frozen fruit. LTB of fruit stored at −0.5 °C for 24 weeks was 27% and corresponded to LTB induced at harvest by exposure at −2 °C for 24 h. The results of this study confirm that LTB is inducible by low but not freezing temperatures at harvest and therefore it might be considered as the physiological basis towards the development of an LTB incidence index for harvested kiwifruit. Copyright © 2006 Society of Chemical Industry