bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lauroyl peroxide as thermal initiator of lauryl methacrylate monolithic columns for CEC
Authors: Cantó‐Mirapeix Amparo , Herrero‐Martínez José M. , Mongay‐Fernández Carlos , Simó‐Alfonso Ernesto F. 
Published: October 2008

AbstractThe preparation of lauryl methacrylate (LMA)‐based monolithic columns for CEC using lauroyl peroxide (LPO) as thermal initiator of polymerization has been investigated. The influence of initiator amount and composition of porogenic solvent on the physical and electrochromatographic properties of the resulting LMA‐based monoliths was evaluated. A comparison with LMA‐based columns thermally polymerized with AIBN was performed. At a given porogenic solvent composition, LMA stationary phases initiated with LPO showed higher permeabilities and better efficiency values than those prepared using AIBN as initiator. The optimum polymerization mixture found for LPO initiator provided a minimum plate height of 9.5 μm in a polycyclic aromatic hydrocarbon mixture. The produced monolithic beds also exhibited a good run‐to‐run repeatability and column‐to‐column and mixture‐to‐mixture reproducibility, with RSD values below 5.3% for the retention factors, areas and plate heights.
Downregulation of P2X7receptor expression in rat oligodendrocyte precursor cells after hypoxia ischemia
Authors: Wang Li‐Yan , Cai Wen‐Qin , Chen Peng‐Hui , Deng Qi‐Yue , Zhao Cong‐Min 
Published: October 2008

AbstractOligodendrocyte precursor cells (OPCs) are the predominant oligodendrocyte‐lineage stage in the cerebral hemispheres of neonatal rat. Prior studies have shown that OPCs are highly vulnerable to hypoxic‐ischemic injury, yet the mechanisms are not well understood. P2X7receptor (P2X7R) is an ATP‐gated ion channel that has unusual properties and plays very complex roles in a variety of neuropathologic conditions. However, little is known about the involvement of P2X7R in OPCs development and injury. The present study was aimed at examining the presence of P2X7R in OPCs and evaluating the change of the receptor expression after hypoxia ischemia. Using Immunofluorescence, RT‐PCR, and western blot analysis, we demonstrated that OPCs expressed P2X7Rin vitroandin vivo. Activation of P2X7R in OPCs in response to 3′‐O‐(4‐benzoyl) benzoyl‐ATP (BzATP) led to an increased mobilization of intracellular calcium [Ca2+]i, formation of large pores and cell death. These functional responses were sensitive to pretreatment of cells with the P2X7R antagonist, Brilliant Blue G (BBG, 100 nM), which was a selective antagonist for P2X7R in nanomole range. A decrease in P2X7R expression was observed in cultured OPCs after exposure to oxygen‐glucose deprivation (OGD) for 2 hin vitro. Using a neonatal hypoxic‐ischemic injury model in postnatal 3 rats, the similar downregulation was also detected in ischemic cerebral cortex, subcortical white matter and hippocampus compared with sham operation controls. In conclusion, the present data demonstrated that OPCs expressed functional P2X7R. The post‐ischemic downregulation of P2X7R suggested a role for this receptor in the pathophysiology of hypoxic‐ischemic brain injury. © 2008 Wiley‐Liss, Inc.
TNF‐α‐ and TRAIL‐resistant glioma cells undergo autophagy‐dependent cell death induced by activated microglia
Authors: Mora Rodrigo , Abschuetz Anette , Kees Tim , Dokic Ivana , Joschko Natalie , Kleber Susanne , Geibig Renate , Mosconi Eric , Zentgraf Hanswalter , Martin‐Villalba Ana , Régnier‐Vigouroux Anne 
Published: October 2008

AbstractThe role of microglia, the brain resident macrophages, in glioma biology is still ill‐defined. Despite their cytotoxic potential, these cells that significantly infiltrate the tumor mass seem to support tumor growth rather than tumor eradication. A proper activation of microglia anti‐tumor activities within the tumor may provide a valuable additional arm of defense to immunotherapies against brain tumors. We herewith report a detailed characterization of (lipopolysaccharide and interferon‐gamma)‐induced anti‐tumor activities of mouse primary microglia towards two TNF‐alpha and TRAIL resistant glioma cell lines, in cell monolayer or spheroid cultures and in collagen‐embedded tumor explants. Irrespective of the mouse strain, stimulated microglia secreted proteic factors that decreased proliferation and migration of these glioma cells and efficiently killed them. Death occurred specifically in glioma cells as demonstrated by the lack of toxicity of microglia supernatant towards primary cultures of astrocytes or neurons. Cell death was characterized by the early accumulation of acidic vesicles, phosphatidylserine exposure, appearance of double‐membrane cytoplasmic vesicles, extensive zeiosis and a very late loss of DNA in cells that had lost membrane integrity. Inhibition of autophagosome formation efficiently protected glioma cells from death whereas caspase inhibition could only prevent DNA loss but not cytotoxicity. Death however, resulted from a blockade by microglia supernatant of the basal autophagic flux present in the glioma cells. These observations demonstrate that glioma cells resistant to apoptotic death ligands could be successfully and specifically killed through autophagy‐dependent death induced by appropriately activated microglia. © 2008 Wiley‐Liss, Inc.
Astrocyte cultures exhibit P2X7 receptor channel opening in the absence of exogenous ligands
Authors: Nagasawa Kazuki , Escartin Carole , Swanson Raymond A. 
Published: October 2008

AbstractP2X7 receptors (P2X7Rs) gate the opening of large channels when activated by ATP or other ligands. P2X7Rs are expressed by astrocytes in culture and by reactive astrocytes in vivo, and astrocytes in culture have been shown to release glutamate and ATP in response to P2X7R activation. However, P2X7Rs are activated by ATP only at concentrations greater than 1 mM. The conditions under which astrocyte P2X7Rs would be activated in vivo are, thus, unclear. Here we show that astrocytes in culture exhibit basal P2X7R activity. Primary mouse astrocytes were found to take up the P2X7R permeant dyes YO‐PRO‐1 (YP) and propidium iodide in absence of any added ligands. By contrast, cultured rat astrocytes took up very little YP, consistent with their much lower level of P2X7R expression. The uptake by mouse astrocytes was inhibited by oxATP, suramin, KN‐62 and brilliant blue G, and by siRNA knock‐down of P2X7R. Astrocyte uptake of YP was also inhibited by phenol red at concentrations above 50 μM, suggesting that phenol red present in standard cell culture media may influence P2X7R channel activity. Treatment with apyrase, an enzyme that degrades extracellular ATP, partially decreased YP uptake in astrocytes. Conversely, exposure to the ectonucleotidase inhibitor ARL67156 enhanced YP uptake and astrocytes plated without contiguous neighboring astrocytes showed reduced basal YP uptake. These results suggest that the basal uptake of YP may be due to activation of P2X7R by release of ATP by astrocytes themselves into intercellular spaces. © 2008 Wiley‐Liss, Inc.
Climate variability, snow, and physiographic controls on storm hydrographs in small forested basins, western Cascades, Oregon
Authors: Perkins Reed M. , Jones Julia A. 
Published: October 2008

AbstractLarge floods are often attributed to the melting of snow during a rain event. This study tested how climate variability, snowpack presence, and basin physiography were related to storm hydrograph shape in three small (<1 km2) basins with old‐growth forest in western Oregon. Relationships between hydrograph characteristics and precipitation were tested for approximately 800 storms over a nearly 30‐year period. Analyses controlled for (1) snowpack presence/absence, (2) antecedent soil moisture, and (3) hillslope length and gradient. For small storms (<150 mm precipitation), controlling for precipitation, the presence of a snowpack on near‐saturated soil increased the threshold of precipitation before hydrograph rise, extended the start lag, centroid lag, and duration of storm hydrographs, and increased the peak discharge. The presence of a snowpack on near‐saturated soil sped up and steepened storm hydrographs in a basin with short steep slopes, but delayed storm hydrographs in basins with longer or more gentle slopes. Hydrographs of the largest events, which were extreme regional rain and rain‐on‐snow floods, were not sensitive to landform characteristics or snowpack presence/absence. Although the presence of a snowpack did not increase peak discharge in small, forested basins during large storms, it had contrasting effects on storm timing in small basins, potentially synchronizing small basin contributions to the larger basin hydrograph during large rain‐on‐snow events. By altering the relative timing of hydrographs, snowpack melting could produce extreme floods from precipitation events whose size is not extreme. Further work is needed to examine effects of canopy openings, snowpack, and climate warming on extreme rain‐on‐snow floods at the large basin scale. Copyright © 2008 John Wiley & Sons, Ltd.
Aryl hydrocarbon receptor polymorphism modulates DMBA‐induced inflammation and carcinogenesis in phenotypically selected mice
Authors: De Souza Vinicius R.C. , Cabrera Wafa K. , Galvan Antonella , Ribeiro Orlando G. , De Franco Marcelo , Vorraro Francisca , Starobinas Nancy , Massa Solange , Dragani Tommaso A. , Ibañez Olga M. 
Published: October 2008

AbstractWe tested the role of aryl hydrocarbon receptor (Ahr) gene polymorphism in the inflammatory response and in skin and lung tumorigenesis in 2 lines of mice phenotypically selected for maximum or minimum acute inflammatory reaction (AIRmax and AIRmin, respectively). Following 7,12‐dimethylbenz[a]anthracene (DMBA) treatment, AIRmin but not AIRmax mice showed early skin reactions and eventually developed malignant skin tumors and lung adenocarcinomas. In skin tissue, transcript levels of IL1β, Tnf, Il6, Tgfβ1 and Cyp1b1 genes were upregulated in AIRmin but not AIRmax mice, consistent with the inflammatory responses to the carcinogen. These findings appeared to be related to the homozygosity status of the Ahr functional A375V polymorphism, which influences the binding capability of the receptor for DMBA: the 375A allele, encoding the high‐affinity ligand‐binding receptor (Ahrb1), segregated in AIRmin mice, whereas AIRmax mice carried the 375V, corresponding to the low‐affinity binding receptor (Ahrd), to DMBA. The differential segregation of Ahr functional Ahrdversus Ahrb1 alleles in AIRmax and AIRmin suggests a role for the Ahr gene in the control of inflammatory responsiveness and tumor development of these mouse lines. © 2008 Wiley‐Liss, Inc.
IL‐13 cytotoxin has potent antitumor activity and synergizes with paclitaxel in a mouse model of oral squamous cell carcinoma
Authors: Kioi Mitomu , Shimamura Takeshi , Nakashima Hideyuki , Hirota Makoto , Tohnai Iwai , Husain Syed R. , Puri Raj K. 
Published: October 2008

AbstractInterleukin‐13 receptor‐targeted cytotoxin (IL13‐PE38) is highly cytotoxic to certain types of human cancers expressing abundant levels of IL‐13Rα2 chain. Although IL13‐PE38 is being tested in a Phase III clinical trial in brain tumors, the activity of IL13‐PE38 alone or when combined with taxane, a chemotherapeutic drug for oral squamous cell carcinoma (OSCC), has not been investigated. Here, we show that approximately 40% of OSCCs (n = 50) in a tissue array are strongly positive for IL‐13Rα2, whereas normal oral mucosa (n = 10) expresses very low or undetectable levels evaluated by immunohistochemistry. IL13‐PE38 was highly cytotoxic to OSCC cell lines, but not cytotoxic to normal oral fibroblasts. IL13‐PE38 mediated a synergistic antitumor effect with paclitaxel in OSC‐19 in vitro and in vivo in the orthotopic OSCC tongue tumor model. Real‐time tumor growth was monitored by optical imaging using a Xenogen‐IVIS imaging system. Treated animals showed significant (p < 0.05) improvement in survival, which correlated with in vivo imaging of tumor response without evidence of visible toxicity. Gene transfer of IL‐13Rα2 in oral cancer cells increased sensitivity of OSCC cell line to IL13‐PE38 in vitro. Retrovirus‐mediated gene‐transfer of IL‐13Rα2 in HSC‐3 into tongue tumors in vivo dramatically enhanced the antitumor activity of IL13‐PE38, providing complete elimination of established tumors and prolonging survival of these animals. These results indicate that IL13‐PE38 in combination with paclitaxel acting via different mechanisms may be a potential treatment option for IL‐13Rα2 expressing OSCC or for the treatment of non–IL‐13Rα2 expressing OSCC combined with gene transfer of IL‐13Rα2. Published 2008 Wiley‐Liss, Inc.
Sensitization of neuroblastoma cells for TRAIL‐induced apoptosis by NF‐κB inhibition
Authors: Ammann Johannes U. , Haag Christian , Kasperczyk Hubert , Debatin Klaus‐Michael , Fulda Simone 
Published: October 2008

AbstractThe transcription factor nuclear factor‐kappaB (NF‐κB) plays a central role in stress‐induced transcriptional activation and has been implicated in chemoresistance of cancers. In the present study, we investigated the role of NF‐κB in inducible chemoresistance of neuroblastoma. Doxorubicin, VP16 and the cytotoxic ligand TRAIL trigger NF‐κB activation, whereas cisplatin and taxol have no impact on NF‐κB activity. Specific inhibition of NF‐κB activation by overexpression of dominant‐negative mutant IκBα‐super‐repressor does not alter cell death upon doxorubicin or VP16 treatment, although it prevents doxorubicin‐ or VP16‐mediated NF‐κB activation. By comparison, inhibition of TRAIL‐stimulated NF‐κB activation by IκBα‐superrepressor or the small molecule NF‐κB inhibitor BMS‐345541 significantly enhances TRAIL‐induced apoptosis, pointing to an antiapoptotic function of NF‐κB in TRAIL‐mediated apoptosis. Analysis of signaling pathways reveals that NF‐κB inhibition prevents TRAIL‐triggered up‐regulation of Mcl‐1, promoting TRAIL‐induced cytochrome c release and activation of caspases. Accordingly, knockdown of Mcl‐1 by RNA interference significantly enhances TRAIL‐induced apoptosis and also increases sensitivity of neuroblastoma cells to CD95‐ or chemotherapy‐induced apoptosis. In conclusion, NF‐κB regulates apoptosis in a stimulus‐specific manner in neuroblastoma cells and confers protection against TRAIL‐induced apoptosis. By demonstrating that NF‐κB inhibition sensitizes neuroblastoma cells for TRAIL‐induced apoptosis, our findings have important implications. Thus, NF‐κB inhibitors may open new perspectives to potentiate the efficacy of TRAIL‐based protocols in the treatment of neuroblastoma. © 2008 Wiley‐Liss, Inc.
Aberrant expression of proteinase‐activated receptor 4 promotes colon cancer cell proliferation through a persistent signaling that involves Src and ErbB‐2 kinase
Authors: Gratio Valérie , Walker Francine , Lehy Thérèse , Laburthe Marc , Darmoul Dalila 
Published: October 2008

AbstractThrombin is now recognized as an important factor in many cancers. Here, we examined the expression and role of the recently discovered thrombin receptor PAR4, in human colon cancer cells. PAR4 mRNA was found in 10 out of 14 (71%) human colon cancer cell lines tested but not in epithelial cells isolated from normal human colon. This finding is in line with immunostaining results of PAR4 in human colon tumors and its absence in normal human colonic mucosa. Investigation of the functional significance of the aberrant expression of PAR4 in colon cancer cells revealed (i) a prompt increase in intracellular calcium concentration on challenge with PAR4‐specific agonist AP4 (100 μM) and (ii) marked mitogenic response (2.5‐fold increase in cell number) in a dose‐dependent manner on treatment with AP4 (0.1–300 μM). Analysis of the signaling pathways downstream of PAR4 activation in HT29 cells showed (i) a sustained phosphorylation of extracellular signal‐related kinase 1/2 (ERK1/2) and (ii) the involvement of epidermal growth factor receptor B‐2 (ErbB‐2) but not of epidermal growth factor receptor in PAR4‐induced mitogen‐activated protein kinase activation. Tyrphostin AG1478, the ErbB inhibitor, reversed the action of AP4 on ERK1/2 and ErbB‐2 phosphorylation and HT29 cell growth. Finally, the Src inhibitor PP2 abrogated ErbB‐2 and ERK phosphorylation and HT29 cell proliferation, suggesting the essential role of Src activity in PAR4‐induced phosphorylation of ErbB‐2. These data highlight the role of PAR4 as a new important player in the control of colon tumors and underline the critical role of ErbB‐2 transactivation. © 2008 Wiley‐Liss, Inc.
Dysregulated microRNAs and their predicted targets associated with endometrioid endometrial adenocarcinoma in Hong Kong women
Authors: Chung Tony K.H. , Cheung Tak‐Hong , Huen Ngar‐Yee , Wong Katherine W.Y. , Lo Keith W.K. , Yim So‐Fan , Siu Nelson S.S. , Wong Yin‐Mei , Tsang Po‐Ting , Pang Man‐Wah , Yu Mei‐Yun , To Ka‐Fei , Mok Samuel C. , Wang Vivian W. , Li Chen , Cheung Albert Y.K. , Doran Graeme , Birrer Michael J. , Smith David I. , Wong Yick‐Fu 
Published: October 2008

AbstractThe objective of this study, a parallel study to global gene expression profiling, was to identify dysregulated microRNAs (miRNAs) associated with endometrioid endometrial adenocarcinoma (EEC), examine their correlation with clinico‐pathological characteristics and identify predicted target genes of the dysregulated miRNAs. Using real‐time quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR), profiling of miRNA expression was performed in 30 EECs and 22 normal counterparts in which genome‐wide gene expression had been previously profiled and reported. Clustering analysis identified 30 miRNAs which were significantly dysregulated in EEC. The expression of a sub‐group of miRNAs was significantly correlated with clinico‐pathological characteristics including stage, myometrial invasion, recurrence and lymph node involvement. By searching for predicted miRNA targets that were linked to the dysregulated genes previously identified, 68 genes were predicted as candidate targets of these 30 dysregulated miRNAs. miR‐205 was significantly overexpressed in EECs compared with normal controls. After transfection of a miR‐205 inhibitor, the expression of miR‐205 in endometrial cancer cell line RL95‐2 cells decreased whereas its predicted target gene, JPH4, showed increased protein expression. JPH4 seems to be a real miR‐205 target in vitro and in vivo, and a candidate tumor suppressor gene in EEC. Based on this study in EEC, miRNAs predicted to be involved in tumorigenesis and tumor progression have been identified and placed in the context of the transcriptome of EEC. This work provides a framework on which further research into novel diagnosis and treatment of EEC can be focused. © 2008 Wiley‐Liss, Inc.
HINT1 inhibits β‐catenin/TCF4, USF2 and NFκB activity in human hepatoma cells
Authors: Wang Lin , Li Haiyang , Zhang Yujing , Santella Regina M. , Weinstein I. Bernard 
Published: October 2008

AbstractIn this study we explored the relevance of Hint, a novel tumor suppressor gene, to human hepatoma. The human hepatoma cell lines Hep3B and HepG2 express very low levels of the HINT1 protein but the Huh7 cells express a relatively high level. In Hep3B and HepG2 cells, but not in Huh7 cells, the promoter region of Hint1 is partially methylated and treatment with 5‐azadcdeoxycytidine increased expression of the HINT1 protein and Hint1 mRNA in Hep3B and HepG2 cells. Increased expression of HINT1 in HepG2 cells markedly inhibited their growth. It also inhibited the transcriptional activities of β‐catenin/TCF4, and USF2, and inhibited the expression of endogenous cyclin D1 and TGFβ2. Furthermore, HINT1 co‐immunoprecipitated with USF2 in extracts of Hep2 cells. HINT1 also inhibited NFκB transcription factor reporter activity and inhibited translocation of the endogenous p65 protein to the nucleus of HepG2 cells. Therefore, decreased expression of the Hint1 gene through epigenetic silencing may play a role in enhancing the growth of a subset of human hepatoma by increasing the expression of genes controlled by the transcription factors β‐catenin, USF2, and NFκB. © 2008 Wiley‐Liss, Inc.
Hormone escape is associated with genomic instability in a human prostate cancer model
Authors: Legrier Marie‐Emmanuelle , Guyader Charlotte , Céraline Jocelyn , Dutrillaux Bernard , Oudard Stéphane , Poupon Marie‐France , Auger Nathalie 
Published: October 2008

AbstractLack of hormone dependency in prostate cancers is an irreversible event that occurs through generation of genomic instability induced by androgen deprivation. Indeed, the cytogenetic profile of hormone‐dependent (HD) prostate cancer remains stable as long as it received a hormone supply, whereas the profile of hormone‐independent (HID) variants acquired new and various alterations. This is demonstrated here using a HD xenografted model of a human prostate cancer, PAC120, transplanted for 11 years into male nude mice and 4 HID variants obtained by surgical castration. Cytogenetic analysis, done by karyotype, FISH, CGH and array‐CGH, shows that PAC120 at early passage presents numerous chromosomal alterations. Very few additional alterations were found between the 5th and 47th passages, indicating the stability of the parental tumor. HID variants largely maintained the core of chromosomal alterations of PAC120 — losses at 6q, 7p, 12q, 15q and 17q sites. However, each HID variant displayed a number of new alterations, almost all being specific to each variant and very few shared by all. None of the HID had androgen receptor mutations. Our study indicates that hormone castration is responsible for genomic instability generating new cytogenetic abnormalities susceptible to alter the properties of cancer cell associated with tumor progression, such as increased cell survival and ability to metastasize. © 2008 Wiley‐Liss, Inc.
Over‐expression of phosphatase of regenerating liver‐3 correlates with tumor progression and poor prognosis in nasopharyngeal carcinoma
Authors: Zhou Jun , Wang Shuang , Lu Juan , Li Jianming , Ding Yanqing 
Published: October 2008

AbstractThis study aimed at clarifying the expression of phosphatase of regenerating liver‐3 (PRL‐3), one member of protein tyrosine phosphatase (PTP) superfamily, in nasopharyngeal carcinoma (NPC) and its correlation with clinicopathologic features, including the survival of patients with NPC. Real‐time PCR and Western blot showed that the expression level of PRL‐3 was markedly higher in NPC cell lines than that in the normal nasopharyngeal epithelial cell at both mRNA and protein levels. Immunohistochemical analysis revealed overexpression of PRL‐3 in 97 of 174 (55.7%) paraffin‐embedded archival NPC biopsies. Statistical analysis showed that PRL‐3 expression was positively correlated with N classification (p = 0.033), distant metastasis (M classification, p = 0.048) and clinical stage (p = 0.005) of patients. Patients with higher PRL‐3 expression had shorter overall survival time, whereas patients with lower level of PRL‐3 had better survival. Multivariate analysis suggested that PRL‐3 expression might be an independent prognostic indicator for the survival of patients with NPC. Disruption of endogenous PRL‐3 protein through a siRNA knockdown technique was shown to suppress the invasion ability and migration potency of 5‐8F and HONE1 cells, substantially. Interestingly, we also found that no significant effect on the proliferation of 5‐8F and HONE1 cells was observed after PRL‐3 was down‐regulated. Our results suggest that PRL‐3 protein is a valuable marker for progression of NPC patients. High PRL‐3 expression is associated with poor overall survival in patients with NPC. © 2008 Wiley‐Liss, Inc.