bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relationship between E‐cadherin gene mutation and p53 gene mutation, p53 accumulation, Bcl‐2 expression and Ki‐67 staining in diffuse‐type gastric carcinoma
Authors: Fricke Elena , Keller Gisela , Becker Ingrid , Rosivatz Erika , Schott Christina , Plaschke Susanne , Rudelius Martina , Hermannstädter Christine , Busch Raymonde , Höfler Heinz , Becker Karl‐Friedrich , Luber Birgit 
Published: January 2003

AbstractE‐cadherin mutations are found in 50% of diffuse‐type gastric carcinoma, but not in intestinal gastric carcinoma. Because cell–cell adhesion mediated by E‐cadherin plays an important role in epithelial cell survival, E‐cadherin mutations could alter the apoptotic behavior of tumor cells. p53 and Bcl‐2 family members are also important regulators of cellular apoptosis. This is the first study that investigates the relationship between E‐cadherin gene mutation and p53 gene mutation, p53 accumulation, Bcl‐2 expression, and Ki‐67 expression in diffuse‐type gastric carcinoma (24 cases, E‐cadherin mutation status: wild‐type in 8 patients and mutant in 16 patients). The mutation status of exons 5–8 of p53 was analyzed by denaturing high pressure liquid chromatography (DHPLC) in formalin‐fixed, paraffin‐embedded tumor sections, followed by direct sequencing of cases with aberrant chromatographic patterns. p53 mutations were found in 1 of 8 tumors without E‐cadherin mutation (12.5%) and in 1 of 16 tumors with E‐cadherin mutation (6.3%), a difference that was not statistically significant (p = 1.00). p53 accumulation was found in 8 of 24 tumors (33.3%) by immunohistochemical staining. p53 accumulation was significantly more frequent in tumors without E‐cadherin mutations (5 of 8 tumors, 62.5%) than in gastric carcinoma tissues with E‐cadherin mutations (3 of 16 tumors, 18.8%, p = 0.03). Bcl‐2 staining was not observed in gastric carcinoma cells without E‐cadherin mutations, but was detectable in 5 of 16 tumors with E‐cadherin mutations (31.3%), a difference that was not statistically significant (p = 0.13). No relationship was observed between Ki‐67 staining and the E‐cadherin mutation status (p = 1.00). These data suggest that the presence of E‐cadherin mutations can significantly alter the accumulation of the apoptose‐regulating p53 protein, whereas no correlation with the p53 mutation status or with Ki‐67 staining was observed. © 2002 Wiley‐Liss, Inc.
Age‐dependent variations of human and rat colon myofibroblasts in culture: Influence on their functional interactions with colon cancer cells
Authors: Pourreyron Céline , Dumortier Jérôme , Ratineau Christelle , Nejjari Mimoun , Beatrix Olivier , Jacquier Marie‐France , Remy Lionel , Chayvialle Jean‐Alain , Scoazec Jean‐Yves 
Published: January 2003

AbstractEpithelial–mesenchymal interactions play a pivotal role in colon cancer invasion and metastasis. We aimed at elucidating the impact of long‐term cultivation on the phenotypic and functional characteristics of primary fibroblasts and their interaction with the human colon adenocarcinoma cell line LoVoC5. We used fibroblasts from human colon tumor tissue, normal human colon mucosa, rat normal colon and 2 rat colon‐derived myofibroblast cell lines, MIC316 and MG. The following parameters were studied: cell shape and size, growth curve, intermediate filament expression and extracellular matrix synthesis. Coculture models with or without cell contacts were used to test the effects on LoVoC5 cell proliferation, spreading and adhesion. Irrespective of their origin, fibroblastic cells in primary cultures presented marked phenotypic and functional changes with time. Before passage 5, they presented as large, slow‐growing cells expressing vimentin and α‐smooth muscle actin; synthesizing laminin‐1, fibronectin and collagens I and IV; and inducing LoVoC5 proliferation, spreading and adhesion. After passage 15, they presented as small, fast‐growing cells inconstantly expressing α‐smooth muscle actin and synthesizing mainly type I collagen. In coculture with or without cell contacts, they inhibited LoVoC5 proliferation and allowed only limited cell spreading and adhesion. Myofibroblastic cell lines presented as large, fast‐growing cells expressing vimentin and α‐smooth muscle actin and synthesizing mainly type I collagen. They had no significant effects on LoVoC5 proliferation, spreading and adhesion. Our results underline the importance of age‐dependent variations in colon mesenchymal cells in culture and for the in vitro study of epithelial–mesenchymal interactions in colon cancer. © 2002 Wiley‐Liss, Inc.
Cannabinoids inhibit gap junctional intercellular communication and activate ERK in a rat liver epithelial cell line
Authors: Upham Brad L. , Rummel Alisa M. , Carbone Joseph M. , Trosko James E. , Ouyang Yanli , Crawford Robert B. , Kaminski Norbert E. 
Published: January 2003

AbstractMany tumor promoters suppress the immune system; however, the direct effect of immunosuppressants on the tumorigenic pathways of nonimmune cells in solid tissue has not been well documented. Cannabinoids were chosen to explore this question further. Cannabinoids are immune modulators that affect specific intracellular signaling pathways in leukocytes. Since these compounds are nongenotoxic, any tumorigenic effect that might be associated with these compounds would need to occur through an epigenetic mechanism. Therefore, we determined the effect of Δ9‐THC and CBN, 2 plant‐derived cannabinoids, on 2 key epigenetic markers of tumor promotion: inhibition of GJIC, which is essential in removing a cell from growth suppression, and activation of the ERK–MAPK pathway, which is crucial in activating the appropriate genes for mitogenesis. Both Δ9‐THC and CBN reversibly inhibited GJIC at noncytotoxic doses (15 μM) in a normal diploid WB rat liver epithelial oval cell line within 20 min and activated ERK1 and ERK2 within 5 min. Inhibition of MEK with PD98059 prevented the inhibition of GJIC by either cannabinoid, suggesting that inhibition of GJIC was MEK‐dependent. Based on RT‐PCR analysis and employment of an antagonist of CB1 and CB2, the effects on GJIC and MAPK were independent of both cannabinoid receptors. Cannabinoids affected crucial epigenetic pathways associated with cell proliferation in a rodent liver epithelial cell model system. © 2002 Wiley‐Liss, Inc.
Dynamic T1‐weighted monitoring of vascularization in human carcinoma heterotransplants by magnetic resonance imaging
Authors: Kiessling Fabian , Heilmann Melanie , Vosseler Silvia , Lichy Matthias , Krix Martin , Fink Christian , Kiessling Isabel , Steinbauer Heinrich , Schad Lothar , Fusenig Norbert E. , Delorme Stefan 
Published: January 2003

AbstractStudies on tumor angiogenesis and antiangiogenic therapies are commonly performed with tumor heterotransplants in nude mice. To monitor therapeutic effects, improved noninvasive analyses of functional data are required, in addition to the assessment of tumor volume and histology. Here, we report on sequential monitoring of vascularization of human squamous cell carcinomas growing as heterotransplants in nude mice using MRI. Using a custom‐developed animal coil in a conventional whole‐body 1.5 T MRI scanner, dynamic T1w sequences were recorded after i.v. injection of Gd‐DTPA in tumors grown for 17, 21, 25, 29 and 33 days. Amplitude and the exchange rate constant (kep) were calculated according to a 2‐compartment model, discriminating intravascular and interstitial spaces, and correlated with tumor size and histology. High‐resolution imaging of small heterotransplants from 100 to 1,000 mm3 was achieved, clearly discriminating vital and necrotic areas. Preceding the development of necroses, which were hyperintense in T2w images and confirmed with histology, a local decrease of amplitude and kep values was observed. Significantly higher amplitudes were found in tumor periphery than in central parts, correlating well with the vascular pattern obtained by immunocytochemistry. Tumor size correlated negatively with amplitude, probably as a result of increasing necrotic areas, whereas the reason for the observed increase of kep value with tumor size remains unclear. These data demonstrate that dynamic MRI is an excellent method for noninvasive assessment of tumor vascularization in small animals using a clinical whole‐body scanner with little technical modifications. This technique provides functional data characterizing essential features of tumor biology and is thus appropriate for monitoring antiangiogenic therapies. © 2002 Wiley‐Liss, Inc.
Activation of multiple caspases and modification of cell surface fas (CD95) in proteasome inhibitor‐induced apoptosis of rat natural killer cells
Authors: Lu Min , Kitson Richard P. , Xue Yaming , Goldfarb Ronald H. 
Published: January 2003

AbstractThe proteasome is a multi‐subunit protease complex that is involved in intracellular protein degradation in eukaryotes. Previously, we have reported that selective, synthetic chymotryptic proteasome inhibitors inhibit A‐NK cell‐mediated cytotoxicity by approximately 50%; however, the exact role of the proteasome in NK cell‐mediated cytotoxicity remains unknown. Herein, we report that proteasome inhibitors, MG115 and MG132, decreased the proteasome chymotrypsin‐like activity in the rat natural killer cell line RNK16 by 85% at a concentration of 5 μM. The viability of RNK16 cells was also reduced in the presence of these inhibitors. Both inhibitors induced the apoptosis of RNK16 cells, as shown by DNA fragmentation, caspase‐3 activation and the appearance of sub‐G‐cell populations. An increase in the fraction of apoptotic cells was observed in a dose‐ and time‐dependent manner in our studies. In addition, the activity of caspase‐1, ‐2, ‐6, ‐7, ‐8, and ‐9, was increased following the treatment of RNK16 cells with these inhibitors. Further investigation revealed that the expression of Fas (CD95) protein on the RNK16 cell surface was increased after the treatment by MG115 or MG132, indicating that apoptosis induced by proteasome inhibitors in RNK16 cells might be mediated through the Fas (CD95)‐mediated death pathway as well. Our studies indicate, for the first time, that proteasomal chymotryptic inhibitors can reduce natural killer cell viability and therefore indirectly inhibit cell‐mediated cytotoxicity via the apoptosis‐inducing properties of these agents. © 2002 Wiley‐Liss, Inc.
Myosin heavy chain kinase B participates in the regulation of myosin assembly into the cytoskeleton
Authors: Rico Maribel , Egelhoff Thomas T. 
Published: January 2003

AbstractMyosin II plays critical roles in events such as cytokinesis, chemotactic migration, and morphological changes during multicellular development. The amoeba Dictyostelium discoideum provides a simple system for the study of this contractile protein. In this system, myosin II filament assembly is regulated by myosin heavy chain (MHC) phosphorylation in the tail region of the molecule. Earlier studies identified an alpha‐kinase, MHC kinase A (MHCK A), which phosphorylates three mapped threonine residues in the myosin tail, driving myosin disassembly. Using molecular and genomic approaches, we have identified a series of related kinases in Dictyostelium. The enzyme MHCK B shares with MHCK A a domain organization that includes a highly novel catalytic domain coupled to a carboxyl‐terminal WD repeat domain. We have engineered, expressed, and purified a FLAG‐tagged version of the novel kinase. In the present study, we report detailed biochemical and cellular studies documenting that MHCK B plays a physiological role in the control of Dictyostelium myosin II assembly and disassembly during the vegetative life of Dictyostelium amoebae. The presented data supports a model of multiple related MHCKs in this system, with different regulatory mechanisms and pathways controlling each enzyme. © 2002 Wiley‐Liss, Inc.
Regulation of the osteoblast‐specific transcription factor, Runx2: Responsiveness to multiple signal transduction pathways
Authors: Franceschi Renny T. , Xiao Guozhi 
Published: January 2003

AbstractThe Cbfa1/Runx2 is an important transcription factor necessary for osteoblast differentiation and bone formation. However, the signaling pathways regulating Runx2 activity are just beginning to be understood. Inconsistencies between Runx2 mRNA or protein levels and its transcriptional activity suggests that posttranslational modification and/or protein‐protein interactions may regulate this factor. Runx2 can be phosphorylated and activated by the mitogen‐activated protein kinase (MAPK) pathway. This pathway can be stimulated by a variety of signals including those initiated by extracellular matrix (ECM), osteogenic growth factors like bone morphogenic proteins (BMPs) and fibroblast growth factor‐2 (FGF‐2), mechanical loading and hormones such as parathyroid hormone (PTH). Protein kinase A (PKA) may also phosphorylate/activate Runx2 under certain conditions. In addition, Runx2 activity is enhanced by protein‐protein interactions as are seen with PTH‐induced Runx2/AP‐1 and BMP‐mediated Runx2/Smads interactions. Mechanisms for interaction with Runx2 are complex including binding of distinct components such as AP‐1 factors and Smads proteins to separate DNA regions in target gene promoters and direct physical interactions between Runx2 and AP‐1/Smad factors. Post‐translational modifications such as phosphorylation may influence interactions between Runx2 and other nuclear factors. These findings suggest that Runx2 plays a central role in coordinating multiple signals involved in osteoblast differentiation. © 2002 Wiley‐Liss, Inc.
Changes of sphingolipid species in the phenotype conversion from myofibroblasts to lipocytes in hepatic stellate cells
Authors: Andrade Claudia M.B. , Trindade Vera M.T. , Cardoso Carla C.A. , Ziulkoski Ana L. , Trugo Luiz C. , Guaragna Regina M. , Borojevic Radovan , Guma Fátima C.R. 
Published: January 2003

AbstractSphingolipids play a relevant role in cell–cell interaction, communication, and migration. We studied the sphingolipid content in the murine hepatic stellate cell line GRX, which expresses the myofibroblast phenotype, and can be induced in vitro to display the fat‐storing phenotype. Lipid modifications along this induction were investigated by labeling sphingolipids with [14C]galactose, [14C]serine, or [14C]choline, and determination of fatty acid composition of sphingomyelin. The total ganglioside content and the GM2 synthase activity were lower in myofibroblasts. Both phenotypes presented similar gangliosides of the a‐pathway: GM2, GM1, and GD1a as well as their precursor GM3. Sphingomyelin and all the gangliosides were expressed as doublets; the upper/lower band ratio increased in lipocytes, containing more long‐chain fatty acids in retinol‐induced lipocytes as compared to the insulin/indomethacin induced ones. Time‐course experiments indicated a transfer of metabolic precursors from phosphatidylcholine to sphingomyelin in the two phenotypes. Taken together, these results indicate that myofibroblast and lipocytes can use distinct ceramide pools for sphingolipid synthesis. Differential ganglioside expression and presence of the long‐chain saturated fatty acids suggested that they may participate in formation of distinct membrane microdomains or rafts with specific functions on the two phenotypes of GRX‐cells. © 2002 Wiley‐Liss, Inc.
Nuclear lipids: New functions for old molecules?
Authors: Martelli Alberto M. , Tabellini G. , Borgatti P. , Bortul R. , Capitani S. , Neri L.M. 
Published: January 2003

AbstractIt is becoming increasingly evident that stimulation of nuclear lipid metabolism plays a central role in many signal transduction pathways that ultimately result in various cell responses including proliferation and differentiation. Nuclear lipid metabolism seems to be at least as complex as that existing at the plasma membrane. However, a distinctive feature of nuclear lipid biochemical pathways is their operational independence from their cell periphery counterparts. Although initially it was thought that nuclear lipids would serve as a source for second messengers, recent evidence points to the likelihood that lipids present in the nucleus also fulfil other roles. The aim of this review is to highlight the most intriguing advances made in the field over the last year, such as the production of new probes for the in situ mapping of nuclear phosphoinositides, the identification of two sources for nuclear diacylglycerol production, the emerging details about the peculiar regulation of nuclear phosphoinositide synthesizing enzymes, and the distinct possibility that nuclear lipids are involved in processes such as chromatin organization and pre‐mRNA splicing. © 2003 Wiley‐Liss, Inc.
Immunohistochemical analysis of Bin1/Amphiphysin II in human tissues: Diverse sites of nuclear expression and losses in prostate cancer
Authors: DuHadaway James B. , Lynch Frank J. , Brisbay Shawn , Bueso‐Ramos Carlos , Troncoso Patricia , McDonnell Timothy , Prendergast George C. 
Published: January 2003

AbstractThe Bin1/Amphiphysin II gene encodes at least seven alternately spliced adapter proteins that have been implicated in membrane dynamics and nuclear processes. Nuclear localized Bin1 polypeptides have tumor suppressor and proapoptotic activities, suggesting that Bin1 may suppress cancer in tissues where nuclear expression may occur. One question is the extent to which human tissues express nuclear Bin1 isoforms. A secondary issue has been the need for a specific antibody that can detect all the splice isoforms expressed by the human, mouse, and rat Bin1 genes. Using a novel mouse monoclonal antibody with these characteristics, we performed an immunohistochemical analysis of Bin1 expression in a panel of normal human tissues. We also compared the expression profile of Bin1 in normal or malignant tissues derived from human prostate, where Bin1 is a candidate tumor suppressor gene. In brain, a distinct nuclear staining pattern overlapped with a cytosolic staining pattern present in certain layers of the cerebral cortex and cerebellum. Bone marrow cells displayed mainly nuclear localization whereas peripheral lymphoid cells exhibited mainly cytosolic localization. In several epithelial tissues, nuclear or nucleocytosolic staining patterns were displayed by basal cells in skin, breast, or prostate, whereas cytosolic or plasma membrane‐associated staining patterns were noted in gastrointestinal cells. Interestingly, a striking gradient of expression was observed in gastrointestinal epithelia, particularly in the large intestine, with the strongest staining displayed by cells destined to undergo apoptosis at the villus tip. In prostate, Bin1 staining was frequently absent in cases of primary prostate adenocarcinoma. This study used a novel reagent to document the extent of expression of nuclear Bin1 isoforms, which exhibit cancer suppression and proapoptotic activity in human cells. © 2002 Wiley‐Liss, Inc.
Effect of stream segregation on ozonation for the removal of significant COD fractions from textile wastewater
Authors: Doǧruel Serdar , Germirli‐Babuna Fatoş , Kabdaşlı Işık , Insel Güçlü , Orhon Derin 
Published: January 2003

AbstractOzonation was tested on selected streams of cotton finishing textile plant wastewater for optimizing chemical oxygen demand (COD) removal. For this purpose, significant COD fractions in the wastewater were experimentally identified and the effect of ozone on these fractions was investigated. Ozonation experiments were performed with a 1 dm3 sample volume. Ozone treatment of batches of raw wastewater provided, at a rate of 62 mg min−1 and a gas feeding time of 15 min, achieved complete colour removal but only 21% COD reduction. Increasing the feeding time to 30 min slightly increased the COD removal to 32%. At this feeding time, removal of the readily biodegradable COD was 60%, but soluble inert COD reduction remained at 16%, indicating selective preference of ozone for simpler compounds. At low concentrations, ozone was mainly influential on soluble COD compounds. Longer feeding times also affected particulate compounds, resulting in the solubilization of the COD fractions. Pre‐ozonation of the dye‐house wastewater, as a segregated stream, proved much more effective in the breakdown of refractory organic compounds, rendering the overall plant effluent more amenable to biological treatment.© 2002 Society of Chemical Industry
Performance characteristics of mechanical foam‐breakers fitted to a stirred‐tank reactor
Authors: Takesono Satoshi , Onodera Masayuki , Yoshida Masanori , Yamagiwa Kazuaki , Ohkawa Akira 
Published: January 2003

AbstractIn a stirred‐tank reactor (STR), a comparison of the performance of mechanical foam‐breakers: a six‐blade turbine (F‐B), a six‐blade vaned disk (V‐D), a two‐blade paddle (T‐P), a conical rotor (C‐R), a fluid‐impact dispersion apparatus (FIDA) and a rotating disk mechanical foam‐breaker (MFRD) was carried out using defined foaming media. The foam‐breaking ranges (relative to the gas superficial velocity, Ug) of the T‐P, C‐R and FIDA were inferior to that of the F‐B, V‐D and MFRD. The power consumption, Pkc, for foam‐breaking in the MFRD was the lowest among the F‐B, V‐D and MFRD. Operation of the F‐B and V‐D in the STR caused a considerable amount of liquid droplets from the collapsed foam to be entrained with the exhaust air.© 2002 Society of Chemical Industry
Degradation of color photographic waste fix solution by anodic oxidation
Authors: Ragauskas Romas , Dikčius Arvydas , Vengris Tomas , Padarauskas Audrius 
Published: January 2003

AbstractBy use of a capillary electrophoretic method for anion analysis the anodic oxidation of thiosulfate, present in color photo bleach‐fix solutions, was investigated. In a specially constructed electrolysis cell with a cation‐exchange membrane separating the electrode chambers and with a carbon flow‐through three‐dimensional anode the two‐stage anodic oxidation of S2O32− anions was realized. In the first stage, S2O32− anions were oxidized to a maximal degree to an intermediate compound – tetrathionate (S4O62−) – then S4O62− anions were oxidized to the sulfate (SO42−), avoiding the decomposition of intermediate compounds and the formation of harmful sulfur compounds.© 2002 Society of Chemical Industry