bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cooperative expression of junctional adhesion molecule‐C and ‐B supports growth and invasion of glioma
Authors: Tenan Mirna , Aurrand‐Lions Michel , Widmer Valerie , Alimenti Alessandro , Burkhardt Karim , Lazeyras François , Belkouch Marie‐Claude , Hammel Philippe , Walker Paul R. , Duchosal Michel A. , Imhof Beat A. , Dietrich Pierre‐Yves 
Published: September 2009

AbstractBrain invasion is a biological hallmark of glioma that contributes to its aggressiveness and limits the potential of surgery and irradiation. Deregulated expression of adhesion molecules on glioma cells is thought to contribute to this process. Junctional adhesion molecules (JAMs) include several IgSF members involved in leukocyte trafficking, angiogenesis, and cell polarity. They are expressed mainly by endothelial cells, white blood cells, and platelets. Here, we report JAM‐C expression by human gliomas, but not by their normal cellular counterpart. This expression correlates with the expression of genes involved in cytoskeleton remodeling and cell migration. These genes, identified by a transcriptomic approach, include poliovirus receptor and cystein‐rich 61, both known to promote glioma invasion, as well as actin filament associated protein, a c‐Src binding partner. Gliomas also aberrantly express JAM‐B, a high affinity JAM‐C ligand. Their interaction activates the c‐Src proto‐oncogene, a central upstream molecule in the pathways regulating cell migration and invasion. In the tumor microenvironment, this co‐expression may thus promote glioma invasion through paracrine stimuli from both tumor cells and endothelial cells. Accordingly, JAM‐C/B blocking antibodies impair in vivo glioma growth and invasion, highlighting the potential of JAM‐C and JAM‐B as new targets for the treatment of human gliomas. © 2009 Wiley‐Liss, Inc.
Proteomic analysis of astroglial connexin43 silencing uncovers a cytoskeletal platform involved in process formation and migration
Authors: Olk Stephan , Turchinovich Andrey , Grzendowski Michael , Stühler Kai , Meyer Helmut E. , Zoidl Georg , Dermietzel Rolf 
Published: September 2009

AbstractConnexin43 (Cx43) is the most abundant gap junction protein of the brain, where it is predominantly expressed in astrocytes. Recent studies imply a role of Cx43 in the regulation of important cellular processes, including migration, proliferation, and shape formation. These processes are assumed to be reflected by the proteome of the Cx43 expressing cells. To analyze the influence of Cx43 on the astrocytic proteome, we used RNA interference to downregulate the expression of this connexin in cultures of mouse astrocytes. We applied difference gel electrophoresis (DIGE) to compare silenced astrocytes with control cells. The differential proteome analysis revealed 15 significantly regulated proteins (between 1.2‐ and 1.6‐fold), of which six are known to belong to a group of cytoskeletal proteins involved in cortical platform formation. Astrocytes treated with Cx43 small interfering (si)RNA showed an increased expression of the cytoskeletal proteins: actin, tropomyosin, microtubule‐associated protein RP/EB1, transgelin, and GFAP, and a decreased expression of cofilin‐1. Quantitative immunocytochemistry and Western blotting revealed similar results showing an upregulation of actin, tubulin, tropomyosin, EB1, transgelin and GFAP, and a downregulation of Ser‐3‐phosphorylated cofilin. Furthermore, Cx43 silencing led to phenotypical changes in cell morphology, migratory activity, and cell adhesion. Our results provide mechanistic clues for an understanding of Cx43 interaction with cellular motor activities such as migration and process formation in astrocytes. © 2009 Wiley‐Liss, Inc.
Injection of fresh river water into a saline floodplain aquifer in an attempt to improve the condition of river red gum (Eucalyptus camaldulensis Dehnh.)
Authors: Berens Volmer , White Melissa G. , Souter Nicholas J. 
Published: September 2009

AbstractThe delivery of environmental flows to riverine floodplains is often constrained by water scarcity and infrastructure. This means that areas of floodplain are unable to receive environmental water through mechanisms like dam release, weir pool surcharge and artificial flooding of low lying areas. This study trials aquifer injection as a method of providing environmental flows to areas of stressed river red gum (Eucalyptus camaldulensis) on the floodplain of the lower River Murray. The objective was to inject fresh river water at the top of the saline alluvial aquifer to reduce root zone salinity and improve the condition of E. camaldulensis. Localized radial freshening of ∼10 m was observed at each of the five injection wells when 4·9 Ml (megalitres) of river water was injected into the aquifer over 45 days. Injection was abandoned after 45 days due to aquifer and well clogging, and increases in groundwater head, which caused four of the five wells to breach the confining clay layer. The trial resulted in localized and short‐lived freshening of the groundwater, which reduced salinity in the associated capillary fringe. This did not result in an improvement in the tree condition as they lay beyond the lateral extent of the freshening and were unable to access the water. Solutions to technical issues such as aquifer clogging and well breaching, as well as a need to increase the lateral extent of freshening, are required before shallow aquifer injection can be recommended as a method of delivering environmental flows. Copyright © 2009 John Wiley & Sons, Ltd.
Altered molecular pathways in melanocytic lesions
Authors: Scatolini Maria , Grand Maurizia Mello , Grosso Enrico , Venesio Tiziana , Pisacane Alberto , Balsamo Antonella , Sirovich Roberta , Risio Mauro , Chiorino Giovanna 
Published: September 2009

AbstractTo identify gene expression changes in melanocytic lesions, biopsies from 18 common nevi (CMN), 11 dysplastic nevi (DN), 8 radial and 15 vertical growth phase melanomas (RGPM, VGPM), and 5 melanoma metastases (MTS) were analyzed using whole genome microarrays. The comparison between CMN and RGPM showed an enrichment of Gene Ontology terms related to inter and intracellular junctions, whereas the transition from RGPM to VGPM underlined the alteration of apoptosis. Upregulation of genes involved in dsDNA break repair and downregulation of cellular adhesion genes were observed in MTS with respect to VGPM. DN exhibited rather heterogeneous molecular profiles, with some proliferation genes expressed at higher levels than in CMN, altered regulation of transcription compared to RGPM and a subset of processes, such as mismatch repair, equally expressed as in VGPM. Furthermore, the expression profile of genes involved into cellular detoxification and antigen presentation split them into two classes, with different proliferation potential. Finally, molecular profiling of individual lesions identified altered biological processes, such as regulation of apoptosis, regulation of transcription and T‐cell activation, not associated with specific histological classes but rather with subgroups of samples without apparent relationship. This holds true for dysplastic nevi in particular. Our data indicate that generally the intersection between stage specific and sample specific molecular alterations may lead to a more precise determination of the individual progression risk of melanocytic lesions.
Beneficial and detrimental effects of human endogenous retroviruses
Authors: Kurth Reinhard , Bannert Norbert 
Published: September 2009

AbstractIn this mini review, we aim to evaluate the structure and function of Human Endogenous Retroviruses (HERVs) with respect to the benefit they may have for humans or the damage they may cause. Emphasis is laid on their putative roles, if any, in pregnancy, in gene regulation and in cancer. As a basis for this discussion it will first be necessary to briefly describe the structure and function of retroelements, including HERVs, before addressing their positive or negative effects at the cellular and organismal level. Finally, we will give an outlook in which we will attempt to define priorities for future research.
Sunlight, hormone replacement status and colorectal cancer risk in postmenopausal women
Authors: Freedman D. Michal , Rajaraman Preetha , Fuhrman Barbara , Hoffbeck Richard , Alexander Bruce H. 
Published: September 2009

AbstractA reanalysis of the Women's Health Initiative (WHI) randomized clinical trial found a significant interaction between supplementation with vitamin D/calcium and estrogen therapy and the risk of colorectal cancer risk, with reduced risks from supplementation limited to the placebo arms of the estrogen trials. To explore whether the vitamin D effects are modified by estrogen therapy, we report a largely cross‐sectional, analysis of the association between sun exposure, which is an important vitamin D source, and colorectal cancer risk among postmenopausal women in the U.S. Radiologic Technologists study. Among 21,695 participants, there were a total of 108 cases. Sun exposure was based on time outdoors and on ambient ultraviolet radiation (UV) exposure based on residence linked to erythemal exposures derived from the Total Ozone Mapping Spectrometer database. Although there was no relationship between outdoor time or ambient UV measure and colorectal cancer risk in current hormone replacement therapy (HRT) users, in never/past HRT users, there was an inverse association with higher ambient UV exposure, RR for highest vs. lowest tertile = 0.40; 95% CI 017, 0.93; p for trend = 0.04. Non‐significant lower risks were also associated with higher levels of outdoor time (≥3.5 hr/week) in never/past HRT users. The interaction between both indicators of sun exposure and HRT and CRC risk was not significant. These data, although exploratory, are consistent with evidence from the WHI suggesting a decrease in colorectal cancer risk may be associated with vitamin D exposure among postmenopausal women who are not taking HRT, but not among current HRT users.
Kallikrein‐related peptidase‐4 initiates tumor–stroma interactions in prostate cancer through protease‐activated receptor‐1
Authors: Wang Wenbin , Mize Gregory J. , Zhang Xiaotun , Takayama Thomas K. 
Published: September 2009

AbstractIn prostate cancer, the mechanism by which the stromal cells surrounding the cancer epithelium become reactive and overproduce growth factors is unclear. Furthermore, the precise process of how these stromal cells stimulate the cancer epithelium is not fully understood. We recently found that protease‐activated receptor‐1 (PAR‐1) in these reactive stromal cells is upregulated. To investigate the role of PAR‐1 in the stromal–epithelial interaction, WPMY‐1 stromal myofibroblasts were stimulated with PAR‐1 agonists including thrombin and PAR‐1 activating peptide. We show that WPMY‐1 cells have functional PAR‐1 by signaling through ERK1/2. Conditioned media (CM) from PAR‐1 agonists‐treated WPMY‐1 cells stimulate the epithelial LNCaP cells leading to ERK1/2 activation and cell proliferation. Cytokine array analysis of the CM demonstrates that PAR‐1 induces stromal cells to release numerous cytokines, of which interleukin 6 (IL‐6) is the major factor responsible for mitogenic signaling in LNCaP cells. CM further induces expression of prostate‐specific kallikrein‐related peptidase‐3 (KLK3/PSA) and KLK4 in LNCaP cells via the IL‐6 pathway. Moreover, KLK4 functions as a potent agonist of PAR‐1 by cleaving the receptor at the proper site on cell surface. KLK4 triggers transmembrane signaling and upregulates IL‐6 in WPMY‐1 cells through PAR‐1. Immunohistochemical analysis indicates that PAR‐1 is predominantly expressed in peritumoral stroma while KLK4 is produced exclusively by the epithelial cancer cells. These data provide evidence for a novel double‐paracrine mechanism whereby cancer epithelium produces KLK4 to activate PAR‐1 in the surrounding stroma, which in‐turn releases cytokines (IL‐6) that stimulate cancer cells to proliferate and increase production of KLKs.
Increased local dopamine secretion has growth‐promoting effects in cholangiocarcinoma
Authors: Coufal Monique , Invernizzi Pietro , Gaudio Eugenio , Bernuzzi Francesca , Frampton Gabriel A. , Onori Paolo , Franchitto Antonio , Carpino Guido , Ramirez Jonathan C. , Alvaro Domenico , Marzioni Marco , Battisti Guido , Benedetti Antonio , DeMorrow Sharon 
Published: September 2009

AbstractCholangiocarcinoma is a devastating cancer of biliary origin with limited treatment options. Symptoms are usually evident after blockage of the bile duct by the tumor, and at this late stage, they are relatively resistant to chemotherapy and radiation therapy. Therefore, it is imperative that alternative treatment options are explored. We have previously shown that serotonin metabolism is dysregulated in cholangiocarcinoma leading to an increased secretion of serotonin, which has growth‐promoting effects. Because serotonin and dopamine share the degradation machinery, we evaluated the secretion of dopamine from cholangiocarcinoma and its effects on cell proliferation. Using 4 cholangiocarcinoma cell lines and human biopsy samples, we demonstrated that there was an increase in mRNA and protein expression of the dopamine synthesis enzymes tyrosine hydroxylase and dopa decarboxylase in cholangiocarcinoma. There was increased dopamine secretion from cholangiocarcinoma cell lines compared to H69 and HIBEC cholangiocytes and increased dopamine immunoreactivity in human biopsy samples. Furthermore, administration of dopamine to all cholangiocarcinoma cell lines studied increased proliferation by up to 30%, which could be blocked by the pretreatment of the D2 and D4 dopamine receptor antagonists, whereas blocking dopamine production by α‐methyldopa administration suppressed growth by up to 25%. Administration of α‐methyldopa to nude mice also suppressed cholangiocarcinoma tumor growth. The data presented here represent the first evidence that dopamine metabolism is dysregulated in cholangiocarcinoma and that modulation of dopamine synthesis may represent an alternative target for the development of therapeutic strategies.
Leucinostatin A inhibits prostate cancer growth through reduction of insulin‐like growth factor‐I expression in prostate stromal cells
Authors: Kawada Manabu , Inoue Hiroyuki , Ohba Shun‐Ichi , Masuda Tohru , Momose Isao , Ikeda Daishiro 
Published: September 2009

AbstractTargeting stroma in tumor tissues is an attractive new strategy for cancer treatment. We developed in vitro coculture system, in which the growth of human prostate cancer DU‐145 cells is stimulated by prostate stromal cells (PrSC) through insulin‐like growth factor I (IGF‐I). Using this system, we have been searching for small molecules that inhibit tumor growth through modulation of tumor‐stromal cell interactions. As a result, we have found that leucinostatins and atpenins, natural antifungal antibiotics, inhibit the growth of DU‐145 cells cocultured with PrSC more strongly than that of DU‐145 cells alone. In this study we examined the antitumor effects of these small molecules in vitro and in vivo. When DU‐145 cells were coinoculated with PrSC subcutaneously in nude mice, leucinostatin A was found to significantly suppress the tumor growth more than atpenin B. The antitumor effect of leucinostatin A in vivo was not obtained against the tumors of DU‐145 cells alone. RT‐PCR experiments revealed that leucinostatin A specifically inhibited IGF‐I expression in PrSC without effect on expressions of other IGF axis molecules. Leucinostatins and atpenins are known to abrogate mitochondrial functions. However, when we used mitochondrial DNA‐depleted, pseudo‐ρ0 cells, we found that one of leucinostain A actions certainly depended on mitochondrial function, but it actually inhibited the growth of DU‐145 cells more strongly in coculture with pseudo‐ρ0 PrSC and reduced IGF‐I expression in pseudo‐ρ0 PrSC. Taken together, our results suggested that leucinostatin A inhibited prostate cancer cell growth through reduction of IGF‐I expression in PrSC.
Genetic disparity between primary tumours, disseminated tumour cells, and manifest metastasis
Authors: Stoecklein Nikolas H. , Klein Christoph A. 
Published: September 2009

AbstractRecent genetic analyses of paired samples from primary tumours and disseminated tumour cells have uncovered a bewildering genetic disparity. It was therefore proposed that ectopically residing tumour cells disseminate early and develop independently into metastases parallel to the primary tumour. Alternatively, these cells may represent an irrelevant cell population unable to spawn metastases whereas only cells that disseminated late in primary tumour development (which therefore are similar to the primary tumour) will form manifest metastasis. Here, we review comparative analyses of paired samples from primary tumours and disseminated tumour cells or primary tumours and metastases. The data demonstrate a striking disparity, questioning the use of primary tumours as surrogate for the genetics of systemic cancer. In the era of molecular therapies that build upon genetic defects of tumour cells, these data call for a direct diagnostic pathology of systemic cancer.
BMP‐2 modulates β‐catenin signaling through stimulation of Lrp5 expression and inhibition of β‐TrCP expression in osteoblasts
Authors: Zhang Ming , Yan Ying , Lim Yong‐bin , Tang Dezhi , Xie Rong , Chen Ann , Tai Peter , Harris Stephen E. , Xing Lianping , Qin Yi‐Xian , Chen Di 
Published: September 2009

AbstractCanonical BMP and Wnt signaling pathways play critical roles in regulation of osteoblast function and bone formation. Recent studies demonstrate that BMP‐2 acts synergistically with β‐catenin to promote osteoblast differentiation. To determine the molecular mechanisms of the signaling cross‐talk between canonical BMP and Wnt signaling pathways, we have used primary osteoblasts and osteoblast precursor cell lines 2T3 and MC3T3‐E1 cells to investigate the effect of BMP‐2 on β‐catenin signaling. We found that BMP‐2 stimulates Lrp5 expression and inhibits the expression of β‐TrCP, the F‐box E3 ligase responsible for β‐catenin degradation and subsequently increases β‐catenin protein levels in osteoblasts. In vitro deletion of the β‐catenin gene inhibits osteoblast proliferation and alters osteoblast differentiation and reduces the responsiveness of osteoblasts to the BMP‐2 treatment. These findings suggest that BMP‐2 may regulate osteoblast function in part through modulation of the β‐catenin signaling. J. Cell. Biochem. 108: 896–905, 2009. © 2009 Wiley‐Liss, Inc.
Aldosterone up‐regulates 12‐ and 15‐lipoxygenase expression and LDL oxidation in human vascular smooth muscle cells
Authors: Limor Rona , Kaplan Marielle , Sharon Orly , Knoll Esther , Naidich Michal , Weisinger Gary , Keidar Shlomo , Stern Naftali 
Published: September 2009

AbstractSeveral lines of evidence suggest that aldosterone excess may have detrimental effects in the cardiovascular system, independent of its interaction with the renal epithelial cells. Here we examined the possibility that aldosterone modulates 12‐ and/or 15‐lipoxygenase (LO) expression/activity in human vascular smooth muscle cells (VSMC), in vitro, thereby potentially contributing to both vascular reactivity and atherogenesis. Following 24 h treatment of VSMC with aldosterone (1 nmol/L), there was a ∼2‐fold increase in the generation rate of 12 hydroxyeicosatetraenoic acid (12‐HETE), 70% increase in platelet type 12‐LO mRNA expression (P < 0.001) along with a ∼3‐fold increase in 12‐LO protein expression, which were blocked by the mineralocorticoid receptor (MR) antagonists spironolactone (100 nmol/L) and eplerelone (100 nmol/ml). Additionally, aldosterone (1 nmol/L; 24 h) increased the production of 15‐HETE (50%; P < 0.001) and the expression of 15‐LO type 2 mRNA (50%; P < 0.05) (in VSMC). Aldosterone also increased the 12‐ and 15‐LO type 2 mRNA expression in a line of human aortic smooth muscle cells (T/G HA‐VSMC) (60% and 50%, respectively). Aldosterone‐induced 12‐ and 15‐LO type 2 mRNA expressions were blocked by the EGF‐receptor antagonist AG 1478 and by the MAPK‐kinase inhibitor UO126. Aldosterone‐treated VSMC also showed increased LDL oxidation, (∼2‐fold; P < 0.001), which was blocked by spironolactone. In conclusion, aldosterone increased 12‐ and 15‐LO expression in human VSMC, in association with increased 12‐ and 15‐HETE generation and enhanced LDL oxidation and may directly augment VSMC contractility, hypertrophy, and migration through 12‐HETE and promote LDL oxidation via the pro‐oxidative properties of these enzymes. J. Cell. Biochem. 108: 1203–1210, 2009. © 2009 Wiley‐Liss, Inc.
Identification of nuclear structural protein alterations associated with seminomas
Authors: Leman Eddy S. , Magheli Ahmed , Yong Koh Meng Aw , Netto George , Hinz Stefan , Getzenberg Robert H. 
Published: September 2009

AbstractCurrently, there are no specific markers available for the early detection and for monitoring testicular cancer. Based upon an approach that targets nuclear structure, we have identified a set of proteins that are specific for seminomas, which may then have clinical utility for the disease. Utilizing samples obtained from men with no evidence of testicular cancer (n = 5) as well as those with seminomas (n = 6), nuclear matrix proteins were extracted and separated using a high‐resolution two‐dimensional electrophoresis gel system. The proteins were identified by mass spectrometry analysis. These analyses revealed seven nuclear matrix proteins associated with the normal testes, which did not appear in the seminomas. In the seminomas, four nuclear matrix proteins were identified to be associated with the disease that were absent in the normal testes. Mass spectrometric and immunoblot analyses of these proteins revealed that one of the proteins identified in the normal testes appears to be StAR‐related lipid transfer protein 7 (StARD7). In the non‐seminoma tissues, one of the identified proteins appears to be cell division protein kinase 10 (CDK10). Both StarD7 and CDK10 could potentially be involved in cell differentiation and growth, and thus may serve as potential targets for therapy of prognostication of seminomas. This is the first study to examine the role of nuclear structural proteins as potential biomarkers in testicular cancer. We are currently examining the roles of some of the identified proteins as potential biomarkers for the disease. J. Cell. Biochem. 108: 1274–1279, 2009. © 2009 Wiley‐Liss, Inc.