bluuebunny/crossref_metadata_2025_split huggingface dataset:
Controlled Metalation of Self‐Assembled Porphyrin Nanoarrays in Two Dimensions
Authors: Auwärter Willi , Weber‐Bargioni Alexander , Brink Susan , Riemann Andreas , Schiffrin Agustin , Ruben Mario , Barth Johannes V. 
Published: December 2006

AbstractWe report a bottom‐up approach for the fabrication of metallo‐porphyrin compounds and nanoarchitectures in two dimensions. Scanning tunneling microscopy and tunneling spectroscopy observations elucidate the interaction of highly regular porphyrin layers self‐assembled on a Ag(111) surface with iron monomers supplied by an atomic beam. The Fe is shown to be incorporated selectively in the porphyrin macrocycle whereby the template structure is strictly preserved. The immobilization of the molecular reactants allows the identification of single metalation events in a novel reaction scheme. Because the template layers provide extended arrays of reaction sites, superlattices of coordinatively unsaturated and magnetically active metal centers are obtained. This approach offers novel pathways to realize metallo‐porphyrin compounds, low‐dimensional metal‐organic architectures and patterned surfaces which cannot be achieved by conventional means.
WIF1, an inhibitor of the Wnt pathway, is rearranged in salivary gland tumors
Authors: Queimado Lurdes , Lopes Carla S. , Reis Antonio M. C. 
Published: December 2006

AbstractChromosome rearrangements involving 12q13‐15 are frequent among several tumors, including pleomorphic adenomas. The common molecular target for these aberrations is the HMGA2 gene, but various fusion partners of HMGA2 have been reported in tumors. Here we report the identification of the WNT inhibitory factor 1 (WIF1) gene as a novel HMGA2 fusion partner in a salivary gland pleomorphic adenoma. In normal salivary gland tissue WIF1 is expressed at a high level and HMGA2 is not expressed. However, in the pleomorphic adenoma expressing the HMGA2/WIF1 fusion transcript, we observed re‐expression of HMGA2 wild‐type transcripts and very low levels of WIF1 expression. These data suggest a possible synergistic effect between upregulation of HMGA2 and downregulation of WIF1. We screened 13 additional benign and malignant salivary gland tumors and detected WIF1 rearrangement in one out of two carcinomas ex‐pleomorphic adenoma analyzed. In this malignant tumor, the rearrangement of one WIF1 allele coexists with loss of the other allele, a classic signature of a tumor suppressor gene. WIF1 is an antagonist of the Wnt signaling pathway, which plays a critical role in human cancer. In transgenic mouse models, Wnt activation leads to a high frequency of benign and malignant salivary gland tumors. To our knowledge, this is the first report suggesting that WIF1 is a recurrent target in human salivary gland oncogenesis and that downregulation of WIF1 plays a role in the development and/or progression of pleomorphic adenomas. © 2006 Wiley‐Liss, Inc.
Molecular characterization of human multiple myeloma cell lines by integrative genomics: Insights into the biology of the disease
Authors: Lombardi Luigia , Poretti Giulia , Mattioli Michela , Fabris Sonia , Agnelli Luca , Bicciato Silvio , Kwee Ivo , Rinaldi Andrea , Ronchetti Domenica , Verdelli Donata , Lambertenghi‐Deliliers Giorgio , Bertoni Francesco , Neri Antonino 
Published: December 2006

AbstractTo investigate the patterns of genetic lesions in a panel of 23 human multiple myeloma cell lines (HMCLs), we made a genomic integrative analysis involving FISH, and both gene expression and genome‐wide profiling approaches. The expression profiles of the genes targeted by the main IGH translocations showed that the WHSC1/MMSET gene involved in t(4;14)(p16;q32) was expressed at different levels in all of the HMCLs, and that the expression of the MAF gene was not restricted to the HMCLs carrying t(14;16)(q32;q23). Supervised analyses identified a limited number of genes specifically associated with t(4;14) and involved in different biological processes. The signature related to MAF/MAFB expression included the known MAF target genes CCND2 and ITGB7, as well as genes controlling cell shape and cell adhesion. Genome‐wide DNA profiling allowed the identification of a gain on chromosome arm 1q in 88% of the analyzed cell lines, together with recurrent gains on 8q, 18q, 7q, and 20q; the most frequent deletions affected 1p, 13q, 17p, and 14q; and almost all of the cell lines presented LOH on chromosome 13. Two hundred and twenty‐two genes were found to be simultaneously overexpressed and amplified in our panel, including the BCL2 locus at 18q21.33. Our data further support the evidence of the genomic complexity of multiple myeloma and reinforce the role of an integrated genomic approach in improving our understanding of the molecular pathogenesis of the disease. This article contains Supplementary Material available at http://www.interscience.wiley.com/jpages/1045‐2257/suppmat. © 2006 Wiley‐Liss, Inc.
DNA cleavage and Trp53 differentially affect SINE transcription
Authors: Hagan Christy R. , Rudin Charles M. 
Published: December 2006

AbstractAmong the cellular responses observed following treatment with DNA‐damaging agents is the activation of Short Interspersed Elements (SINEs; retrotransposable genetic elements that comprise over 10% of the human genome). By placing a human SINE (the Alu element) into murine cells, we have previously shown that DNA‐damaging agents such as etoposide can induce both upregulation of SINE transcript levels and SINE retrotransposition. A similarly cytotoxic (but not genotoxic) exposure to vincristine was not associated with SINE activation. Here we demonstrate that multiple other genotoxic exposures are associated with upregulation of SINE transcript levels. By comparing the effects of similarly cytotoxic doses of the topoisomerase II inhibitors etoposide and merbarone, we confirm that DNA strand breakage is specifically associated with SINE induction. By evaluating transcription rate and RNA stability, we demonstrate that SINE induction by genotoxic exposure is associated with transcriptional induction and not with transcript stabilization. Finally we demonstrate that SINE induction by genotoxic stress is mediated by a Trp53‐independent pathway, and in fact that Trp53 plays an inhibitory role in attenuating the transcriptional induction of SINE elements following exposure to a genotoxic agent. Together these data support a model in which initial DNA damage can trigger genomic instability due to SINE activation, a response which may be amplified in cancer cells lacking functional TP53. © 2006 Wiley‐Liss, Inc.
Array CGH analysis in primary gastrointestinal stromal tumors: Cytogenetic profile correlates with anatomic site and tumor aggressiveness, irrespective of mutational status
Authors: Wozniak Agnieszka , Sciot Raf , Guillou Louis , Pauwels Patrick , Wasag Bartosz , Stul Michel , Vermeesch Joris Robert , Vandenberghe Peter , Limon Janusz , Debiec‐Rychter Maria 
Published: December 2006

AbstractGastrointestinal stromal tumors (GISTs) comprise a biologically diverse group of neoplasms with respect to activating mutations in either KIT or PDGFRA, histology, anatomical site of origin, and clinical aggressiveness. In this study, we applied the high resolution array‐based comparative genomic hybridization (array‐CGH) technology to 66 primary GISTs (40 gastric and 26 nongastric, 48 with KIT and 18 with PDGFRA mutations) for identification of novel high‐level alterations and for characterization of genotype‐related genomic changes. All cases had genomic imbalances with the highest occurrence of 14q (73%), 1p (62%), 22q (59%), 15q (38%), and 13q (29%) losses. Our data indicate that loss of chromosome 14 and/or 22 is an early change in GIST tumorigenesis irrespective of tumor genotype. Furthermore, DNA copy number changes showed a site dependent pattern. These included lower incidence of losses at 14q (87% vs. 35%), and higher frequency of losses at 1p (45% vs. 85%) and 15q (17% vs. 69%) in nongastric versus gastric site (P < 0.001 for all). However, in the multivariate analysis with adjustment to tumor risk stratification, only the 14q loss site‐dependent pattern of distribution retained its significance. These findings suggest that loss of 14q is a relatively less frequent genetic event in the development of nongastric GISTs, the lack of which is most likely substituted by the accumulation of 1p/15q and other changes. The novel minimal overlapping regions of deletion at 1p (1p36.32‐1p35.2, 1p34.1, and 1p22.1‐1p21.3), 13q (13q14.11‐q14.2 and 13q32.3‐q33.1), and 15q23 were delineated, which point to chromosomal regions that may harbor genes relevant to the development of these neoplasms. © 2006 Wiley‐Liss, Inc.
The M53I mutation in CDKN2A is a founder mutation that predominates in melanoma patients with Scottish ancestry
Authors: Lang Julie , Hayward Nicholas , Goldgar David , Tsao Hensin , Hogg David , Palmer Jane , Stark Mitchell , Tobias Edward S. , MacKie Rona 
Published: December 2006

AbstractGermline mutations in the tumor suppressor gene CDKN2A have been shown to predispose to cutaneous malignant melanoma. The M53I mutation is the most common CDKN2A mutation identified in Scottish melanoma patients and is also found in a small number of families in other countries. The aim of this study was to determine whether the occurrence of this mutation is due to a common ancestor originating from Scotland, and if so, to estimate how long ago the mutation arose. We examined 18 families carrying the M53I mutation: six from Scotland, five from Canada, four from Australia, and three from America. Haplotypes derived from segregation of seven informative microsatellite markers flanking CDKN2A were constructed in each family. Our findings show that 14 of 18 families carry a common ancestral haplotype on which the mutation arose ∼88 generations ago (1‐LOD‐unit support interval 44‐198 generations). This haplotype is very rare in controls, which supports the idea that it is a common founder mutation haplotype. The four M53I families that do not share the consensus haplotype may in fact have arisen from the same founder, but this is potentially obscured by presumed replication slippage for some of the microsatellite markers tested. © 2006 Wiley‐Liss, Inc.
Mitotic control of RUNX2 phosphorylation by both CDK1/cyclin B kinase and PP1/PP2A phosphatase in osteoblastic cells
Authors: Rajgopal Arun , Young Daniel W. , Mujeeb Khawaja A. , Stein Janet L. , Lian Jane B. , van Wijnen Andre J. , Stein Gary S. 
Published: December 2006

AbstractSkeletal development and osteoblast maturation require the phenotype promoting activity of the transcription factor RUNX2, which controls both cell growth and differentiation in osteoblasts. We have recently shown that in actively proliferating cells RUNX2 regulates the expression of specific target genes as cells enter and exit mitosis. In this study, we addressed whether post‐translational modifications of RUNX2 control its activity during mitotic exit. Western blot analysis of proteins from osteoblastic Saos‐2 cells released from mitotic inhibition into early G1 show a phosphatase‐sensitive shift in the mobility of RUNX2 in SDS gels. The slowly migrating hyper‐phosphorylated form of RUNX2 is immunoreactive with a CDK related phospho‐antibody (MPM2) only in mitotic cells and is converted into a faster migrating hypo‐phosphorylated RUNX2 when cells complete mitosis. This conversion is inhibited by okadaic acid, an inhibitor of protein phosphatases 1 and 2 (PP1 and PP2A), but not by deltamethrin which blocks PP2B phosphatase. Mitotic phosphorylation of RUNX2 is sensitive to the CDK inhibitors roscovitine and olomoucine. Furthermore, RUNX2 can directly interact with CDK1 and is phosphorylated in vitro by the CDK1/cyclin B kinase complex. Hence, RUNX2 is hyper‐phosphorylated by CDK1/cyclin B during mitosis, and dynamically converted into a hypo‐phosphorylated form by PP1/PP2A‐dependent dephosphorylation after mitosis to support the post‐mitotic regulation of RUNX2 target genes. J. Cell. Biochem. 100: 1509–1517, 2007. © 2006 Wiley‐Liss, Inc.
Suppression of growth factor expression and human vascular smooth muscle cell growth by small interfering RNA targeting EGR‐1
Authors: Fahmy Roger G. , Khachigian Levon M. 
Published: December 2006

AbstractSmooth muscle cell (SMC) proliferation and migration are key processes that occur in the reparative response to injury after percutaneous coronary intervention and in failed bypass grafts for the treatment of atherosclerosis. In the present study, we generated novel synthetic small interfering RNA (siRNA) molecules targeting the coding region of human early growth response‐1 (EGR‐1) mRNA that attenuate the expression of EGR‐1 and that of fibroblast growth factor‐2 (FGF‐2) and granulocyte‐colony stimulating factor (G‐CSF). These agents suppressed SMC proliferation in a dose‐dependent and non‐toxic manner and blocked SMC regrowth from the wound edge following mechanical injury in vitro. In contrast, the scrambled counterpart did not inhibit SMC proliferation, EGR‐1 protein expression or SMC regrowth after injury. These findings demonstrate that EGR‐1 siRNA can serve as inhibitors of SMC proliferation and wound repair suggesting that these agents may potentially be useful in the control of vascular proliferative disorders. J. Cell. Biochem. 100: 1526–1535, 2007. © 2006 Wiley‐Liss, Inc.
Tumor microenvironment abnormalities: Causes, consequences, and strategies to normalize
Authors: Fukumura Dai , Jain Rakesh K. 
Published: December 2006

AbstractA solid tumor is an organ‐like entity comprised of neoplastic cells and non‐transformed host stromal cells embedded in an extracellular matrix. The expression of various genes is influenced by interactions among these cells, surrounding matrix, and their local physical and biochemical microenvironment. The products encoded by these genes, in turn, control the pathophysiological characteristics of the tumor, and give rise to the abnormal organization, structure, and function of tumor blood vessels. These abnormalities contribute to heterogeneous blood flow, vascular permeability, and microenvironment. Proliferating tumor cells produce solid stress which compresses blood and lymphatic vessels. As a result of vessel leakiness and lack of functional lymphatics, interstitial fluid pressure is significantly elevated in solid tumors. Each of these abnormalities forms a physiological barrier to the delivery of therapeutic agents to tumors. Furthermore, the metabolic microenvironment in tumors such as hypoxia and acidosis hinder the efficacy of anti‐tumor treatments such as radiation therapy and chemotherapy. A judicious application of anti‐angiogenic therapy has the potential to overcome these problems by normalizing the tumor vessels and making them more efficient for delivery of oxygen and drugs. Combined anti‐angiogenic and conventional therapies have shown promise in the clinic. J. Cell. Biochem. 101: 937–949, 2007. © 2006 Wiley‐Liss, Inc.
Temporal evolution of gene expression in rat carotid artery following balloon angioplasty
Authors: Li Jian‐ming , Zhang Xueqing , Nelson Peter R. , Odgren Paul R. , Nelson Janice D. , Vasiliu Calin , Park Jane , Morris Marvin , Lian Jane , Cutler Bruce S. , Newburger Peter E. 
Published: December 2006

AbstractThe success of vascular intervention including angioplasty, stenting, and arterial bypass remains limited by negative remodeling resulted in lumen restenosis. This study was to characterize the global transcription profile reflecting concurrent events along arterial remodeling and neointima formation in a rat carotid artery balloon‐injury model. Expression profiling of injured and control common carotid arteries on days 4, 7, 14 post‐injury that mark the major pathohistological progression stages of neointimal formation were recorded on high‐density oligonucleotide arrays. A subset of genes from microarray‐based data was further studied using quantitative real time RT‐PCR and in situ hybridization with sequential arterial samples from days 1 to 28 post‐injury. The gene‐encoded proteins were validated with Western blot. Besides temporal induction of a large cluster of genes over‐represented by cell proliferation and macromolecule metabolism gene ontology categories, a fast‐evolving inflammation could be demonstrated by the induction of Tgfb and other anti‐inflammatory genes (e.g., C1qtnf3 (C1q and tumor necrosis factor related protein 3 (predicted))) and a shift from type 1 to 2 helper T cell response. The most significant signature of the induced neointimal profile is enrichment of genes functionally related to angiogenesis and extracellular matrix (ECM) remodeling (e.g., Spp1 (secreted phosphoprotein 1), CD44 (CD44 antigen), and Cxcl12 (chemokine (C‐X‐C motif) ligand 12 (stromal cell‐derived factor 1)). Some of the genes represent stress‐responsive mesenchymal stromal cell cytokines. This study highlighted mesenchymal stromal cell cytokines‐driven inflammatory extracellular matrix remodeling, as target processes for potential clinical therapeutic intervention. J. Cell. Biochem. 101: 399–410, 2007. © 2006 Wiley‐Liss, Inc.
Functional properties and intracellular signaling of CCN1/Cyr61
Authors: Chen Ying , Du Xiao‐Yan 
Published: December 2006

AbstractCCN1/Cyr61 is a member of the protein family that can be promptly induced by growth factors. CCN1/Cyr61 promotes cell proliferation, adhesion, and differentiation. It plays important roles in angiogenesis and extracellular matrix production. In addition, CCN1/Cyr61 has many potential functions in tumorigenesis, development, embryo implantation, as well as formation of endometriotic lesions. Expression of CCN1/Cyr61 is regulated by a variety of agents including cytokines, growth factors, steroid hormones, and some drugs. These inducers regulate the transcription of CCN1/Cyr61 through several signaling transduction pathways. CCN1/Cyr61 is able to interact either with the cell itself or the surrounding cells through an autocrine–paracrine mechanism. It has been reported that CCN1/Cyr61 exerts its functions via interacting with at least five integrins as well as heparan sulfate proteoglycan. By activating Wnt, NF‐kappaB, or tyrosine kinase signaling pathways, CCN1/Cyr61 is not only able to control the growth of epithelial cells and fibroblasts, but also induce or suppress apoptosis in a cell type‐specific manner. J. Cell. Biochem. 100: 1337–1345, 2007. © 2006 Wiley‐Liss, Inc.
Microenvironmental influences in melanoma progression
Authors: Lee John T. , Herlyn Meenhard 
Published: December 2006

AbstractAn often overlooked facet of tumor biology research is the involvement of the surrounding tumor microenvironment. Increasing evidence is being presented to support a major role for stromal components in all stages of tumorigenesis including initiation, progression, and metastasis. Melanoma serves as a model for studying cellular and stromal interactions within the tumor microenvironment due to the array of cell types localized to these lesions. Here, we discuss the both the molecular mechanisms, as well as the extracellular and contextual input that contribute to melanoma progression. Special emphasis is given to the assorted cell types and their interactions with the extracellular matrix and adjacent cells. Melanoma progression also initiates development of intralesional hypoxic regions; the relative significance of hypoxia in disease is also addressed. Lastly, a number of laboratories are currently developing innovative strategies to study melanoma within a microenvironmental platform. These promising model systems and their potential for closing current gaps in knowledge of disease are reviewed. The development of such models holds translational value that cannot be achieved with most current systems. J. Cell. Biochem. 101: 862–872, 2007. © 2006 Wiley‐Liss, Inc.
Benzyl butyl phthalate influences actin distribution and cell proliferation in rat Py1a osteoblasts
Authors: Agas Dimitrios , Sabbieti Maria G. , Capacchietti Mariolina , Materazzi Stefano , Menghi Giovanna , Materazzi Giovanni , Hurley Marja M. , Marchetti Luigi 
Published: December 2006

AbstractWe previously reported that transient administration of phthalates induced actin cytoskeleton disruption in Py1a osteoblasts. However, the mechanism of this transient effect was not elucidated. In this study we provided evidence that the actin cytoskeletal re‐established conditions are dependent on new actin expression and synthesis. To assess the role of phthalates in modulating the distribution of actin, confocal and electron microscopy studies were carried out. Results indicated a modification of actin distribution after phthalate administration. In addition, a relation with the nucleoskeletal component lamin A supports the hypothesis that phthalates may participate in regulatory cell processes involving actin in Py1a osteoblasts. The present study also supports the mitogenic effects of phthalates, which involve microfilament disruption, nuclear actin and lamin A. In particular, the increased levels of cyclin D3, which in mammalian cells plays a critical role in G1 to S transition and is a putative proto‐oncogene in benzyl butyl phthalate treated cells, suggested a possible effect of the endocrine disruptor in cancer processes. J. Cell. Biochem. 101: 543–551, 2007. © 2006 Wiley‐Liss, Inc.
In vitro multipotentiality and characterization of human unfractured traumatic hemarthrosis‐derived progenitor cells: A potential cell source for tissue repair
Authors: Lee Sang Yang , Miwa Masahiko , Sakai Yoshitada , Kuroda Ryosuke , Matsumoto Tomoyuki , Iwakura Takashi , Fujioka Hiroyuki , Doita Minoru , Kurosaka Masahiro 
Published: December 2006

AbstractMesenchymal progenitor cells (MPCs) are a very attractive tool in the context of repair and regeneration of musculoskeletal tissue damaged by trauma. The most common source of MPCs to date has been the bone marrow, but aspirating bone marrow from the patient is an invasive procedure. In an attempt to search for alternative sources of MPCs that could be obtained with minimal invasion, we looked into traumatic hemarthrosis of the knee. In this study, we determined whether a population of multipotent MPCs could be isolated from acute traumatic knee hemarthrosis in the absence of intra‐articular fractures. Mononuclear cells were isolated from the aspirated hemarthrosis by density gradient separation, and cultured. We were able to obtain plastic adherent fibroblast‐like cells from the mononuclear cell fractions. Flow cytometry analysis revealed that the adherent fibroblast‐like cells were consistently positive for CD29, CD44, CD105, and CD166, and were negative for CD14, CD34, and CD45. These were similar to control bone marrow stromal cells. These cells could differentiate in vitro into osteogenic, adipogenic, and chondrogenic cells in the presence of lineage‐specific induction factors. In conclusion, acute unfractured traumatic hemarthrosis of the knee contains MPCs with multipotentiality. Because knee hemarthrosis is easy to harvest with minimal pain and without unnecessary invasion, we regard hemarthrosis‐derived cells as an additional progenitor cell source for future tissue engineering and cell‐based therapy in knee injuries. J. Cell. Physiol. 210: 561–566, 2007. © 2006 Wiley‐Liss, Inc.