bluuebunny/crossref_metadata_2025_split huggingface dataset:
Colocalization of the p185HER2 oncoprotein and integrin α6β4 in Calu‐3 lung carcinoma cells
Authors: Campiglio Manuela , Tagliabue Elda , Srinivas Uppugunduri , Pellegrini Rita , Martignone Stefania , Ménard Sylvie , Colnaghi Maria Ines , Lombardi Luciano , Marchisio Pier Carlo 
Published: May 2005

AbstractAnti‐p185HER2 monoclonal antibodies often show intense reactivity with the basement membrane of tumor cells that overexpress the HER2/neu gene product (p185HER2). To evaluate a possible interaction between p185HER2 and adhesion molecules or their receptors, the polarity of p185HER2 was tested in lung carcinoma cell line Calu‐3, which overexpresses this protein, in cultures grown as confluent monolayers or as aggregates. MAb immunostaining patterns indicated that p185HER2 is concentrated on the baso‐lateral membrane of cells and that it colocalizes with the integrin α6β4 at the cell‐cell junctions where laminin is also found. The same membrane region showed intense reactivity with antiphosphotyrosine antibodies. Furthermore, integrin clustering induced by the specific antibody was accompanied by the clustering of p185HER2, as indicated by immunoelectron microscopy, and by a subsequent increase in p185HER2 tyrosine phosphorylation. Treatment with exogenous laminin also resulted in increased basal levels of p185HER2 phosphorylation. These data suggest a physical interaction between the integrin and the oncoprotein that might be functionally relevant in directly controlling the tyrosine phosphorylation of the catalytic domain of p185HER2. © 1994 Wiley‐Liss, Inc.
Progesterone but not ras requires MPF for in vivo activation of MAPK and S6 KII: MAPK is an essential conexion point of both signaling pathways
Authors: Carnero Amancio , Jiménez Benilde , Lacal Juan Carlos 
Published: May 2005

AbstractInduction of mitosis in Xenopus laevis oocytes by hormones and the oncogenic ras‐p21 protein has been shown to correlate with a cascade of phosphorylations of the Ser/Thr family of kinases. However, the exact hierarchy of enzymes and their mutual interdependency has not been fully elucidated yet. We have used the Xenopus laevis system to investigate the mechanism of activation of the Ser/Thr kinases cascade and their relationship. Comparison between progesterone‐induced germinal vesicle breakdown (GVBD), a hallmark of mitosis in oocytes, to that triggered by ras‐p21, revealed the existence of at least two independent mechanisms to activate the MAP kinase enzyme in vivo. While progesterone function is dependent of cdc2 protein kinase activity, ras‐p21 is independent of this enzyme. However, both progesterone and ras‐p21 converge at the MAP kinase level, and depletion of MAP kinase activity inhibits the GVBD and S6 kinase II activation induced by both progesterone and ras‐p21. These results provides further evidence that MAP kinase is a critical step for regulation of the cell cycle in oocytes and a critical point where ras and progesterone signaling converge. © 1994 Wiley‐Liss, Inc.
Human breast and colon cancers exhibit alterations of DNA methylation patterns at several DNA segments on chromosomes 11p and 17p
Authors: Ribieras S. , Song‐Wang X.‐G. , Martin V. , Lointier P. , Frappart L. , Dante R. 
Published: May 2005

AbstractIn breast and colon adenocarcinomas methylation patterns at CCGG sites of several loci located on the short arm of chromosome 11 were determined by Southern blot analysis. Results obtained indicate that all tumor samples (20/20) exihibit DNA methylation changes when compared to their normal counterparts. In colon tumors,i‐globin gene is usually hypomethylated (9/10), whereas Ha‐ras gene, which is located in the same region, retains an unmodified DNA methylation pattern. Hypomethylation of parathyroid hormone (5/10) and catalase genes (4/10) are also frequently detected in colon tumor specimens. For the catalase gene the region around exon is the only one which is affected by these changes. In breast adenocacinoma, modifications of the methylation patterns are less frequently observed. However, hypomethylation of the i‐globin gene is a very common event in these tumors (8/10), and it is also detected (2/2) in lobular carcinoma in situ which is an early step in breast tumorgenesis. In addition, hypermethylation of a CpG island is also observed at the locus 17p13.3 in both colon (5/5) and breast (4/9) adenocarcinomas. In the tumoral tissues which containj a limited amount of CpG. Some of these alterations seen, therefore, to be tumor and sequence specific.
Manipulation of cellular interactions with biomaterials toward a therapeutic outcome: A perspective
Authors: Pierschbacher Michael D. , Polarek James W. , Craig William S. , Tschopp Juerg F. , Sipes Nancy J. , Harper John R. 
Published: May 2005

AbstractManipulation of the Wound healing process and the manner in which tissues interact with inertbiomaterials were both made possible with the discovery of arginine‐glucine (RGD) acid as a major cell recognition signal in the extracellular matrix. Whether promoting cell adhesion can be rationally designed to incorporate both stability and integrin specificity. Synthetic peptides containing this sequence have been linked to biodegradable biopolumers and introduced for the enhancement of dermal and corneal wound healing. By accelerating the healing reaction using RGD‐containing peptides, the quality of regenerted tissue seems to be improved, the extent of fibrosis retricted, and the risk of microbial infection may be reduced. Controlling the degree of fibrosis that often accmmpanies the healing of wounds and the reaction of tissue to foreign materials can also be achieved by natural antagonists of fibrogenic activity of TGF‐beta animal models of kidney fobrosis. There advances in the biotechnology of wound healing and tissue regeneration eventually will have an overal impact on the quality of health care.
Recent progress in immunoisolated cell therapy
Authors: Lysaght Michael J. , Frydel Beata , Gentile Frank , Emerich Dwaine , Winn Shelley 
Published: May 2005

AbstractBiohybrid implalts represent a new class of medical device in which living cells, supported in a hydrogel matrix, and surrounded by semipepmiable membrane, produce and deliver therapeutic reagents tm specific sites wthin a host. First prpmsed in the mid‐1970s for tpeatment modality has progressed rapidly in the past four years and is now being investigated not just for endcrine disorders but also for alleviation of chronic pain, treatment of neurodegenerative disorders, and delivery of neurotrophic factors to sites withil the blood brain barrier, and aq a practical alternative to conventional ex vivo.
Oscillatory behavior of control‐systems of calcium homeostasis in chickens
Authors: Hurwitz S. , Miller Barbara , Norman A. W. 
Published: May 2005

AbstractComputer simulation of calcium homeostasis in chicks predicted an oscillatory behavior of bone calcium flow and kidney 25‐hydroxyvitamin D3‐1 hydroxylase with a periodicity of 56 h and a 9 h phase difference between the two signals. In growing chickens subjected to a light: dark cycle of 22:2 h, and intravenously dosed with 45Ca, the temporal changes in plasma 45Ca could be described by an exponential decline with superimposed diurnal oscillations. The activity of the renal 25‐hydpoxyvitamil D3‐1‐hydroxylase in chicks subjected to a 12:12 h light: dark cycle ALSO followed diupnal oscillations, with a ladir at the beginning of the light period and a peak 12 h later. The production of 1,25‐dihydroxyvitamin D3 by primary cultures of chicken kidney cells mscillated with a periodicity of 5.6 h or shorter. It is suggested that despite the differences in phase and periodicity between the simulation predictions and actual results, the oscillations in both 1‐hydroxylase and bone calcium flow could be coupled through the hormonal systems involved in regulation of plasma calcium.
Expression of cell growth and bone phenotypic genes during the cell cycle of normal diploid osteoblasts and osteosarcoma cells
Authors: McCabe Laura R. , Last T. J. , Lynch Maureen , Lian Jane , Stein Janet , Stein Gary 
Published: May 2005

AbstractEstablishing reuglatory mechanisms that mediate proliferation of osteoblasts while restricting expression of genes asociated with mature bone cell phenotypic properties to post‐proliferative cells is fundamental to understanding skeletal development. To gain insight into relationships between growth control and the developmental expression of genes during osteblast differentiation, we have examined expression of three classes of genes during the cell cycle of normal diploid rat calvarial‐derived osteoblasts and rat osteosarcoma cells (ROS 17/2.8): cell cycle and growth‐related to the biosynthesis, organization, and mineralization of the bone extracellular matrix (e.g., alkaline phosphatase, collagen l, osteocalcin, and osteopontin). In normal diploid osteoblasts as well as in osteosarcoma cells we found that histone genes, required for cell progression, are selectively expressed during S phase. All other genes studied were constitutively expressed both at the transcriptional and posttranscriptional levels. Alkaline phosphatase, an integral membrane protein in both osteoblasts and osteosarcoma cells, exhibited only minimal changes in activity during the osteoblast and osteosarcoma cell cycles. Our findings clearly indicate that despite the loss of normal proliferation‐differentiation interrelationships in osteosarcoma cells, cell cycle regulatin or constitutive expression of growth and phenotypic genes is maintained.
Nongenomic actions of the steroid hormone 1α25‐dihydroxyvitamin D3
Authors: Baran Daniel T. 
Published: May 2005

AbstractRecent studies indicate that the vitamin D hormone, 1α,25‐Dohydroxyvitamin D3 exerts rapid effects (seconds to minutes) in a variety of cell types. These rapid nongenomic actions in osteoblasts include effects on membrance voltage‐gated calcium chananels, phosphlipase C activity, and the sodium/dydrogen antiport. Since the rapid effects occur in osteoblasts that lack the neclear vitamin D receptor, it is postulated that the nongenomic responses to the hormone reflect interaction with a separate, membrane localized signalling system. Preliminary studies demonstrate the presence of a receptor on the membranes of osteoblasts that lack the neclear vitamin D. This membranes receptors recognizes 1 a, 25‐dihyrooxyvitamin D3 and its inaction 1β epimer, but not 25‐hydrovitamin D3. These rapid nongenomic actions generated by interaction with the membrane receptor modulate the effect of the hormone on gene transcription. Thus, the rapid nongenomic pathway may play a regulatory function in modulating the genomic pathways affected by 1 a 25‐dihydroxyvitamin D3.
Mechanisms by which cells of the osteoblast lineage control osteoclast formation and activity
Authors: Martin T. J. , Ng K. W. 
Published: May 2005

AbstractThe cells of bone are of two lineages, the osteoblasts arising from pluripotential mesenchymal cells and osteoclasts from hemopoietic precursors of the monocyte‐macrophage series. Resorption of bone by the multinucleate osteoclast requires the generation of new osteoclastsw and their activation. Many hormones and cytokines are able to promote bone resorption by influencing these processes, but they achieve this without acting directly on osteoclastws. Most evidence indicates that their actions are mediated by cells of the osteoblast lineage. Evidence for hormone‐and cytokine‐induced activation of osteoclasts requiring the mediation of osteoblasts comes from studies of rsorption by isolated osteoclasts. However, consistent evidence for a spiceific “activating factor” is lacking, and the argument is presented that the isolated osteoclast resorption assays have not been shown convincingly to be assays of osteoclast activation. The view is presented that osteoblast‐mediated osteoclast activation is the result of several events in the microenvironment without necessarily requiring the existence of a spicific, essential osteoclast activator. On the other hand, a specific promoter of osteoclast differentiation does seem likely to be a product of cells of the stromal/osteoblast series. Evidence in facour of this comes from studies of osteoclast generation in co‐cultures of osteoblast/stromal cells with hemopoietic cells. Conflicting view, maintaining that osteoclasts can develop from hemooietic cells without stromal intervention, might be explaind by varying criteria used in identification of osteoclasts. Osteoblastic and osteoclastic renewal, and the interactions of these lineages, are central to the process of bone remodeling.
p53 Expression in the carcinogenesis in the oral mucosa
Authors: Girod Sabine C. , Krämer Christoph , Knüfermann Ralf , Krueger Garhard R. F. 
Published: May 2005

AbstractHyperplastic lesions of the oral mucosa such as leukoplakia and oral lichan planus can eventually develop into squamous cell carcinomas. In the clinical treatment of these lesions it would be very important tobe able to predict the biological behaviour of an individual lesion. In 64 hyperplastic lesions and 85 squamous cell carcinomas of the oral mucosa, the expression of the mutant tumor suppressor gene p53and the grade of dysplasia of the lesions.
V‐sis induces Egr‐1 expression by a pathway mediated by c‐Ha‐ras
Authors: Huang Ruo‐Pan , Ngo Lan , Okamura Daryl , Tucker Mark , Adamson Eileen D. 
Published: May 2005

AbstractThe early growth response gene, Egr‐1, is up‐regulated transiently by mitogens and many other simuli in all cells tested. Using NIH3T3 cells conditionally expressing v‐sis from a metallothionein promoter, we show that the addition of Zn2+ stimulates the production of PDGF‐B(v‐sis) and elicits the expression of Egr‐1 in a dose‐dependent and time‐regulated manner. The signal is likely independent of protein kinase C, but depends on tyrosine kinase and other kinase activities and is mediated by c‐Ha‐Ras since the presence of dominant‐negative mutants of Ras and Raf abrogates the induction of Egr‐1 expression by Zn2+. Transiently activated Ras expression in NIH3T3 cells also stimulates the transient expression of Egr‐1, but cells that constitutively express Rass do not have elevated levels of Egr‐1. Transient assays also demonstrated that Zn2+ or activated Ras expression stimulated the activity of a 950 bp Egr‐1 promoter‐reporter gene construct and this is abrogated in the presence of mutant Ras and Raf. The accumulated data show that Egr‐1 gene expression is regulated by multiple mechanisms, as would be needed for putative role in Cell proliferation, in suppression of transformation and in differentiation.
Analysis of regulatory regions in the COL1A1 gene responsible for 1,25‐dihydroxyvitamin D3‐mediated transcriptional repression in osteoblastic cells
Authors: Pavlin Dubravko , Bedalov Antonio , Kronenberg Mark S. , Kream Barbara E. , Rowe David W. , Smith Catharine L. , Pike J. Wesley , Lichtler Alexander C. 
Published: May 2005

AbstractThe synthesis of type 1 colagen in bone cells is inhibited by the calcium‐regulating hormone 1,25‐dihydroxyvitamin D3. Earlier work from our laboratoties has indicated that vitamin D regulation is at the level of transcription, based on result from both nuclear run‐off assays and functional analysis of a hybrid gene consisting of a 3.6 kb COL1A1 promoter fragment fused to the chloraphenicol acetyltransferase reporter gene. In the present study, we investigated the molecular basis for vitamin D‐mediated transcriptional repression of the COL1A1 gene and report the identification of a region within the COL1A1 upstream promoter (the Hindlll‐Pstl restriction fragment between nucleotides‐2295 and ‐1670) which is necessary for 1,25‐dihydroxyvitamin D3 responsiveness in osteoblastic cells. This hormone‐mediated inhibitory effect on the marker gene parallels the inhibition of the endogenous collagen gene. A 41 bp fragment from this region (between nucleotides‐2256 and ‐2216) contains a sequence which is very similar to vitamin D‐responsive elements identified in the osteocalcin gene. Estracts that binds specifically to this 41 bp fragment, as demonstrated by bandshift anslysis. However, deletion of this vitamin D receptor binding region from either a‐3.5 kb or a‐2.3 kb promoter fragment did not abolish vitamin D responsiveness. These results indicate that a vitamin D response element similar to that described for other D responsive genes (osteocalcin and osteopontin) does not alone mediate the repression of COL1A1 by 1,25‐dihydroxyvitamin D3.
Cultured AIDS‐related Kaposi's sarcoma cells retain a proliferative bioenergetic profile but demonstrate reduced cytoprotective capabilities
Authors: Mallery S. R. , Ng‐Bautista C. L. , Lantry L. E. , Ness G. M. , Hegtvedt A. K. , Lazo A. , Bailer R. T. , Hout B. L. , Stephens R. E. , Brierley G. P. 
Published: May 2005

AbstractFeatures of AIDS‐related Kaposi's sarcoma (AIDS‐KS), such as the multifocal presentation at mucosal and epidermal sites subjected to trauma, suggest that AIDS‐KS is initially a reactive hyperplasia that subsequently progresses to a neoplasia. It is recognized that there is an association between sustained states and the subsequent development of neoplasia (e.g., ulcerative colitis/colonic adenocarcinoma). Furthermore, patients who develop AIDS‐KS experience both a constant immune stimulation due to sustained high levelsof virus‐induced cytokines and, because of a sparing effect on their phagoctic cells, retention of the phagocytic inflammatory response. A component of phygocytic activation is the initiation of the oxidative brust, resulting in the generation of reactive oxygen species (ROS), which can be mutagenic to host cells if released beyond the phagolysosome and not inactivated. Our results demonstrate that cultured AIDS‐KS cells possess drcreased cytoprotective capabilities. Relativeto either dermal fibroblasts, or human microvascular endothelial cells (HMECs), AIDS‐KS cells contained significantly lower levels of glutathione, a tripeptide integral in both cytoprotection and maintenance of cellular thiol status. While HMECs increased catalase activity during culture in the cytokine‐rich KS milieu (control medium supplement with conditioned medium from MOT, an TLV II‐infected cell line), AIDS‐KS cells demonstrated reduced catalase function under these conditions. Furthermore, HMEC cultures showed in inherent biochemical responsiveness, by increasing catalase activity following exposure to exaogenous H2(O2). In contrast, the catalase activity of AIDS‐KS cells decreased following (H2O2) challenge. Our results show that an inherent deficiency in cellular cytoprotection is present in AIDS‐KS cells and suggest that oxidant stress may function in the development and progression AIDS‐KS.
TGF‐β regulation of nuclear proto‐oncogenes and TGF‐β gene expression in normal human osteoblast‐like cells
Authors: Subramaniam M. , Oursler M. J. , Rasmussen K. , Riggs B. L. , Spelsberg T. C. 
Published: May 2005

AbstractTransforming growth factor‐β (TGF‐β) is present in high levels in bone and plays an important role in osteoblast growth and differentiation. In order to dissect the molecular mechanisms of action of TGF‐β on osteoblasts, the effects of TGF‐β on the steady state mRNA levels of c‐fos, c‐jun, and jun‐B proto‐oncogenes on normal human osteoblast‐like cells (hOB) and a transformed human osteoblast cell line (MG‐63) were measured. Treatment of hOBs with 2 ng/ml of TGF‐β1 resulted in a rapid increase in c‐fos mRNA levels as early as 15 min post‐treatment. A maximum (10‐fold) increase was observed at 30 min after TGF‐β treatment followed by a decrease to control values. Similar responses were measured whether the cells were rapidly proliferating or quiescent. TGF‐β1 induced jun‐B mRNA levels more gradually with steady increase initially observed at 30 min and a maximum induction measured at 2 h post‐TGF‐β treatment. In contrast, TGF‐β treatment caused a time dependent decrease in the c‐jun mRNA levels, an opposite pattern to that of jun‐B mRNA. Treatment of hOBs with TGF‐β1 in the presence of actinomycin‐D abolished TGF‐β1 induction of c‐fos mRNA, suggesting that TGF‐β action is mediated via transcription. In the presence of cycloheximide, TGF‐β causes super‐induction of c‐fos mRNA at 30 min, indicating that the c‐fos expression by TGF‐β is independent of new protein synthesis. Further, transfection of 3 kb upstream region of jun‐B promoter linked to a CAT reporter gene into ROS 17/2.8 cells was sufficient to be regulated by TGF‐β1. Interestingly, TGF‐β treatment also increased the mRNA levels of TGF‐β1 itself at 4 h post TGF‐β treatment, with a maximum increase observed at 14 h of treatment. TGF‐β1 treatment for 30 min were sufficient to cause a delayed increase in TGF‐β protein secretion within 24 h. These data support that TGF‐β has major effects on hOB cell proto‐oncogene expression and that the nuclear proto‐oncogenes respond as rapid, early genes in a cascade model of hormone action.
Sulfate restriction induces hyposecretion of the adhesion proteoglycan and cell hypomotility associated with increased 35SO42− uptake and expression of a band 3 like protein in the marine sponge, Microciona prolifera
Authors: Kuhns William J. , Popescu Octavian , Burger Max M. , Misevic Gradimir 
Published: May 2005

AbstractSulfate is an important component relating to normal proteoglycan secretion and normal motility in the marine sponge, Microciona prolifera. The following alterations were observed in sponge cells when sulfate free artificial sea water was used as the suspension medium: (1) impairment of aggregation, (2) loss of cell movements, (3) a marked reduction in the secretion of the adhesion proteoglycan (AP). Reversal of this effect occurred if sulfate depleted cells were again rotated in sulfate containing artificial sea water. Motility and reaggregation of sulfate deprived cells could be completely restored by purified AP, but only if cells were first pre‐conditioned in normal sea water. Comparisons of 35SO42− uptake between normal and sulfate deprived cells which had been treated to reduce preformed secretions showed a marked increase in 35SO42− uptake and incorporation which could be greatly augmented in the presence of Ca2+/Mg2+. Excessive retention of AP in sulfate starved cells demonstrated by immunostaining suggested that AP secretion and cellular motility may be controlled by a sulfate dependent secretogogue or that undersulfated AP itself had developed a secretory defect. SDS‐PAGE of Triton treated cellular extracts demonstrated a 116 kDa 35SO42− sulfated band which co‐migrated with AP, but only in extracts derived from sulfate starved cells. Western blots prepared from such extracts incubated in the presence of a monoclonal anti‐band 3 antibody demonstrated labelling of a single 97 kDa band only in material from sulfate deprived cells. The absence of this component in normal cell extracts indicated that this protein may be involved in facilitated sulfate transport. This study lends support to a heretofore unrecognized role for sulfate in cell motility and secretion.