bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor metastasis and the lymphatic vasculature
Authors: Sleeman Jonathan P. , Thiele Wilko 
Published: June 2009

AbstractTumor‐associated lymphatic vessels act as a conduit by which disseminating tumor cells access regional lymph nodes and form metastases there. Lymph node metastasis is of major prognostic significance for many types of cancer, although lymph node metastases are themselves rarely life‐threatening. These observations focus our attention on understanding how tumor cells interact with the lymphatic vasculature, and why this interaction is so significant for prognosis. Tumors interact with the lymphatic vasculature in a number of ways, including vessel co‐option, chemotactic migration and invasion into lymphatic vessels and induction of lymphangiogenesis. Tumor‐induced lymphangiogenesis both locally and in regional lymph nodes has been correlatively and functionally associated with metastasis formation and poor prognosis. The investigation of the molecular regulation of lymphangiogenesis has identified ways of interfering with prolymphangiogenic signaling. Blockade of tumor‐induced lymphangiogenesis in preclinical models inhibits metastasis formation in lymph nodes and often also in other organs, suggesting that blocking the lymphatic route of dissemination might suppress metastasis formation not only in lymph nodes but also in other organs. However, randomized clinical trials that have investigated the efficacy of therapeutic removal of lymph nodes have concluded that lymph node metastases act only as indicators that primary tumors have developed metastatic potential, and do not govern the further spread of metastatic cells. To reconcile these apparently paradoxical observations we suggest a model in which tumor‐induced lymphangiogenesis and lymph node metastasis formation act as indicators that tumors are producing factors that can act systemically to promote metastasis formation in distant organs. © 2009 UICC
Endogenous expression of the sodium iodide symporter mediates uptake of iodide in murine models of colorectal carcinoma
Authors: Gaertner Florian C. , Rohde Franziska , Mueller Jan , Blechert Birgit , Janssen Klaus‐Peter , Essler Markus 
Published: June 2009

AbstractThe sodium iodide symporter (NIS) mediates iodide uptake into the thyroid. Because of this mechanism, differentiated thyroid cancer is susceptible for radioiodine therapy. Functional NIS expression in extrathyroidal tumors has been reported mainly in breast cancer. We screened colorectal tumors for NIS expression and investigated the mechanisms regulating NIS activity. Cell lines were screened for iodide uptake in vitro and NIS expression was evaluated by real‐time RT‐PCR, immunocytochemistry and immunoblotting. Iodide and pertechnetate uptake were evaluated in allograft tumors by biodistribution studies and scintigraphy. Tumors of transgenic mouse models for colorectal cancer harboring mutations in the oncogenes KRAS, β‐catenin or the tumor‐suppressor gene adenomatous‐polyposis coli (APC) were screened for NIS expression by RT‐PCR. In vitro, functional NIS activity was detected in murine CMT93 rectal carcinoma cells and NIS expression was verified on mRNA and protein level. Inhibition of tyrosine kinases increased iodide uptake. Inhibition of tyrosine phosphatases decreased iodide uptake. In vivo, functional NIS expression was preserved in CMT93 tumors and tumor uptake could be enhanced by treatment of mice with tyrosine kinase inhibitors. In transgenic murine models of colorectal cancer, 14% of endogenous tumors expressed elevated levels of NIS mRNA. We conclude that NIS is functionally expressed in a subset of murine colorectal tumors and its activity is regulated by tyrosine phosphorylation. Therefore, with specific tyrosine kinase inhibition, these tumors might be susceptible for radioiodine treatment. Further studies are justified to identify the specific pathways regulating NIS activity and to transfer these findings to human cell lines and tissues. © 2009 UICC
Genome‐wide DNA methylation profiles in liver tissue at the precancerous stage and in hepatocellular carcinoma
Authors: Arai Eri , Ushijima Saori , Gotoh Masahiro , Ojima Hidenori , Kosuge Tomoo , Hosoda Fumie , Shibata Tatsuhiro , Kondo Tadashi , Yokoi Sana , Imoto Issei , Inazawa Johji , Hirohashi Setsuo , Kanai Yae 
Published: June 2009

AbstractTo clarify genome‐wide DNA methylation profiles during hepatocarcinogenesis, bacterial artificial chromosome (BAC) array‐based methylated CpG island amplification was performed on 126 tissue samples. The average numbers of BAC clones showing DNA hypo‐ or hypermethylation increased from noncancerous liver tissue obtained from patients with hepatocellular carcinomas (HCCs) (N) to HCCs. N appeared to be at the precancerous stage, showing DNA methylation alterations that were correlated with the future development of HCC. Using Wilcoxon test, 25 BAC clones, whose DNA methylation status was inherited by HCCs from N and were able to discriminate 15 N samples from 10 samples of normal liver tissue obtained from patients without HCCs (C) with 100% sensitivity and specificity, were identified. The criteria using the 25 BAC clones were able to discriminate 24 additional N samples from 26 C samples in the validation set with 95.8% sensitivity and 96.2% specificity. Using Wilcoxon test, 41 BAC clones, whose DNA methylation status was able to discriminate patients who survived more than 4 years after hepatectomy from patients who suffered recurrence within 6 months and died within a year after hepatectomy, were identified. The DNA methylation status of the 41 BAC clones was correlated with the cancer‐free and overall survival rates of patients with HCC. Multivariate analysis revealed that satisfying the criteria using the 41 BAC clones was an independent predictor of overall outcome. Genome‐wide alterations of DNA methylation may participate in hepatocarcinogenesis from the precancerous stage, and DNA methylation profiling may provide optimal indicators for carcinogenetic risk estimation and prognostication. © 2009 UICC
Recent developments in Fourier Domain Mode Locked lasers for optical coherence tomography: Imaging at 1310 nm vs. 1550 nm wavelength
Authors: Biedermann Benjamin R. , Wieser Wolfgang , Eigenwillig Christoph M. , Huber Robert 
Published: June 2009

AbstractWe report on recent progress in Fourier domain mode‐locking (FDML) technology. The paper focuses on developments beyond pushing the speed of these laser sources. After an overview of improvements to FDML over the last three years, a brief analysis of OCT imaging using FDML lasers with different wavelengths is presented. For the first time, high speed, high quality FDML imaging at 1550 nm is presented and compared to a system at 1310 nm. The imaging results of human skin for both wavelengths are compared and analyzed. Sample arm optics, power on the sample, heterodyne gain, detection bandwidth, colour cut levels and sample location have been identical to identify the influence of difference in scattering and water absorption. The imaging performance at 1310 nm in human skin is only slightly better and the results suggest that water absorption only marginally affects the penetration depth in human skin at 1550 nm. For several applications this wavelength may be preferred. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
In vitro and In vivo studies of local arterial gene delivery and transfection using lipopolyplexes‐embedded stents
Authors: Brito Luis A. , Chandrasekhar Saradha , Little Steven R. , Amiji Mansoor M. 
Published: June 2009

AbstractGene‐eluting stents can have profound impact in the treatment of coronary restenosis, especially when the encoded protein can re‐endothelialize the arterial lumen. In this study, we have examined gene delivery in vitro and in vivo using poly(beta‐amino ester) (PbAE) precondensed plasmid DNA‐containing cationic liposomes or lipopolyplexes (LPP) immobilized on stainless steel meshes and stents using gelatin coatings. In vitro studies using LPP‐immobilized on 50 mm round meshes using type A and B gelatin coatings showed that LPP were efficiently internalized in human aortic smooth muscle cells (SMC) over time, leading to green fluorescent protein (GFP) expression. Type B gelatin coating was found to be more effective in intracellular delivery and transgene expression efficiency and, as such, was used for stent coating. In vivo studies, carried out in iliac artery restenosis model in New Zealand white rabbits, also showed GFP expression in arterial tissues after 24 h of implantation. Based on these encouraging preliminary results, LPP‐based formulations can serve as a safe and effective nonviral gene delivery system for effective treatment of coronary restenosis. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010
Biodegradable nitric oxide‐releasing poly(diol citrate) elastomers
Authors: Zhao Haichao , Serrano M. Concepcion , Popowich Daniel A. , Kibbe Melina R. , Ameer Guillermo A. 
Published: June 2009

AbstractWe have developed novel poly(diol citrate) elastomers, which are capable of providing localized and sustained release of nitric oxide (NO). The elastomer prepolymer was obtained by condensation of citric acid, 1,8‐octanediol, andN,N′‐bis(2‐hydroxyethyl)ethylenediamine at 130°C for 40 min. Films were prepared by solvent casting followed by crosslinking at 80°C for 4 days. Mechanical properties were tested. NO‐releasing expanded poly(tetrafluoroethylene) (ePTFE) vascular grafts were fabricated by coating the graft's lumen with the prepolymer and crosslinking it at 80°C for 4 days prior to diazeniumdiolation. Samples were diazeniumdiolated via exposure to pressurized NO. Cell compatibility was assessed by monitoring the proliferation of porcine aortic smooth muscle cells (PASMC) on the elastomers. Degradation in phosphate buffer saline (PBS) (pH = 7) at 37°C was evaluated for up to 6 weeks. The secondary amine‐containing poly(diol citrate) films had a Young's modulus that ranged from 5.91 to 32.64 MPa, an ultimate tensile stress that ranged from 1.47 to 10.71 MPa, and an elongation at break from 200 to 260%, depending on the content of secondary amine in the feed monomer. These elastomers were degradable and compatible with PASMC. Furthermore, degradation rate was found to be independent of the content of secondary amines in the prepolymer. The NO release from diazeniumdiolated films and ePTFE grafts was sustained for two days. In conclusion, these novel diazeniumdiolated polyester elastomers may be useful in medical devices that require blood contact or control of cell proliferation. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res 2010
Citric acid‐based elastomers provide a biocompatible interface for vascular grafts
Authors: Kibbe Melina R. , Martinez Janet , Popowich Daniel A. , Kapadia Muneera R. , Ahanchi Sadaf S. , Aalami Oliver O. , Jiang Qun , Webb Antonio R. , Yang Jian , Carroll Timothy , Ameer Guillermo A. 
Published: June 2009

AbstractProsthetic vascular bypass grafting is associated with poor long‐term patency rates. Herein, we report on the mid‐term performance of expanded polytetrafluoroethylene (ePTFE) vascular grafts modified with a citric acid‐based biodegradable elastomer. Through a spin‐shearing method, ePTFE grafts were modified by mechanically coating a layer of poly(1,8 octanediol citrate) (POC) onto the luminal nodes and fibrils of the ePTFE. Control and POC‐ePTFE grafts were implanted into the porcine carotid artery circulation as end‐to‐side bypass grafts. Grafts were assessed by duplex ultrasonography, magnetic resonance angiography, and digital subtraction contrast angiography and were all found to be patent with no hemodynamically significant stenoses. At 4 weeks, POC‐ePTFE grafts were found to be biocompatible and resulted in a similar extent of neointimal hyperplasia as well as leukocyte and monocyte/macrophage infiltration as control ePTFE grafts. Furthermore, POC supported endothelial cell growth. Lastly, scanning electron microscopy confirmed the presence of POC on the ePTFE grafts at 4 weeks. Thus, these data reveal that surface modification of blood‐contacting surfaces with POC results in a biocompatible surface that does not induce any untoward effects or inflammation in the vasculature. These findings are important as they will serve as the foundation for the development of a drug‐eluting vascular graft. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010
Modulation of hyaluronan catabolism in chondrocytes by mechanical stimuli
Authors: Tanimoto Kotaro , Kitamura Reiko , Tanne Yuki , Kamiya Takashi , Kunimatsu Ryo , Yoshioka Motoko , Tanaka Nobuaki , Tanaka Eiji , Tanne Kazuo 
Published: June 2009

AbstractHyaluronan (HA) is a component of the extracellular matrices of cartilage contributing to the structural and functional integrity. HA metabolism is regulated by both anabolic and catabolic processes; however, a great deal more of the detail has been unknown yet. The purpose of this study was to clarify the effect of excessive mechanical load on the expression and activity of hyaluronidase (HYAL) in chondrocytes with a special reference to the expressions of IL‐1β and tumor necrosis factor (TNF)‐α. A cyclic tensile load of 22.8% cell elongation, regarded as an excessive mechanical stimulus, was applied to cultured rabbit knee articular chondrocytes. HYAL1, HYAL2, IL‐1β, and TNF‐α mRNA levels were examined by quantitative real‐time PCR analysis. The HYAL activity in culture medium was examined by HA zymography. Both HYAL1 and HYAL2 mRNA levels were upregulated significantly by the loading in cultured chondrocytes. HYAL activity was also enhanced as compared with unloaded controls. The IL‐1β mRNA level was upregulated significantly by the loading, and TNF‐α mRNA level was slightly upregulated. HYAL1 and HYAL2 mRNA levels were upregulated significantly by IL‐1β treatment, resulting in a slight increase in HYAL activity. These results show that the expression of HYAL1 and HYAL2 in articular chondrocytes is enhanced by excessive mechanical stimuli and affected in part by induction of IL‐1β, leading to HA catabolism in articular cartilage. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res 2010
Biocompatibility and modification of the protein‐based adhesive secreted by the Australian frog Notaden bennetti
Authors: Graham Lloyd D. , Danon Stephen J. , Johnson Graham , Braybrook Carl , Hart Noel K. , Varley Russell J. , Evans Margaret D. M. , McFarland Gail A. , Tyler Michael J. , Werkmeister Jerome A. , Ramshaw John A. M. 
Published: June 2009

AbstractWhen provoked, Notaden bennetti frogs secrete a proteinaceous exudate, which rapidly forms a tacky and elastic glue. This material has potential in biomedical applications. Cultured cells attached and proliferated well on glue‐coated tissue culture polystyrene, but migrated somewhat slower than on uncoated surfaces. In organ culture, dissolved glue successfully adhered collagen‐coated perfluoropolyether lenses to debrided bovine corneas and supported epithelial regrowth. Small pellets of glue implanted subcutaneously into mice were resorbed by surrounding tissues, and all of the animals made a full recovery. An initial but transient skin necrosis at the implant site was probably caused by some of the potentially toxic metabolites present in the frog secretion; these include sterols and carotenoids, as well as fatty alcohols, aldehydes, ketones, acids, and aromatic compounds. Removal of the carotenoid pigments did not significantly alter the glue's material properties. In contrast, peroxidase treatment of dissolved glue introduced unnatural crosslinks between molecules of the major protein (Nb‐1R) and resulted in the formation of a soft hydrogel, which was very different to the original material. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010
A novel small animal model for biocompatibility assessment of polymeric materials for use in prosthetic heart valves
Authors: Wang Qiang , McGoron Anthony J. , Pinchuk Leonard , Schoephoerster Richard T. 
Published: June 2009

AbstractA composite polymeric material, poly(styrene‐block‐isobutylene‐block‐styrene) (SIBS) with an embedded reinforcement polyethylene terephthalate (PET) fabric, is undergoing investigation for potential use in a novel heart valve. The purpose of this study was to develop and implement a small animal model to assess the biocompatibility of composite samples in a cardiovascular tissue and blood‐contacting environment. Composite samples were manufactured using dip coating and solvent casting with two coating thicknesses (25 and 50 μm). A novel rat abdominal aorta model was developed to test the dip‐coated samples in a similar pulsatile flow condition to its intended use, and both dip‐coated and solvent‐cast samples were tested using a rat subcutaneous model. Tissue response, defined by degree of cellular infiltration and encapsulation, was minimized when a smooth coating of SIBS shielded the PET fabric from exposure to blood and tissue, and the degree of tissue response was directly correlated with the degree of surface roughness. Surface modification using phospholipid further reduces the tissue response. We have demonstrated the applicability of using a novel rat abdominal aorta model for biocompatibility assessment of polymeric materials that will be used in cardiovascular implants. For the purpose of this study, our results indicate that solvent casting with a 25‐μm SIBS coating thickness will provide optimal biocompatibility for the SIBS valve. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res 2010
Deregulated NFATc1 activity transforms murine fibroblasts via an autocrine growth factor‐mediated Stat3‐dependent pathway
Authors: Lagunas Lucio , Clipstone Neil A. 
Published: June 2009

AbstractThe nuclear factor of activated T cells (NFAT) family of transcription factors has recently been implicated with a role in tumorigenesis. Forced expression of a constitutively active NFATc1 mutant (caNFATc1) has been shown to transform immortalized murine fibroblasts in vitro, while constitutive activation of the NFAT‐signaling pathway has been found in a number of human cancers, where it has been shown to contribute towards various aspects of the tumor phenotype. Here we have investigated the molecular mechanisms underlying the oncogenic potential of deregulated NFAT activity. We now show that ectopic expression of caNFATc1 in murine 3T3‐L1 fibroblasts induces the secretion of an autocrine factor(s) that is sufficient to promote the transformed phenotype. We further demonstrate that this NFATc1‐induced autocrine factor(s) specifically induces the tyrosine phosphorylation of the Stat3 transcription factor via a JAK kinase‐dependent pathway. Interestingly, this effect of sustained NFAT signaling on the autocrine growth factor‐mediated activation of Stat3 is not restricted to murine fibroblasts, but is also observed in the PANC‐1 and MCF10A human cell lines. Most importantly, we find that the shRNA‐mediated depletion of endogenous Stat3 significantly attenuates the ability of caNFATc1 to transform 3T3‐L1 fibroblasts. Taken together, our results afford significant new insights into the molecular mechanisms underlying the oncogenic potential of deregulated NFATc1 activity by demonstrating that constitutive NFATc1 activity transforms cells via an autocrine factor‐mediated pathway that is critically dependent upon the activity of the Stat3 transcription factor. J. Cell. Biochem. 108: 237–248, 2009. © 2009 Wiley‐Liss, Inc.
DNA methylation‐mediated epigenetic control
Authors: Rottach Andrea , Leonhardt Heinrich , Spada Fabio 
Published: June 2009

AbstractDuring differentiation and development cells undergo dramatic morphological and functional changes without any change in the DNA sequence. The underlying changes of gene expression patterns are established and maintained by epigenetic processes. Early mechanistic insights came from the observation that gene activity and repression states correlate with the DNA methylation level of their promoter region. DNA methylation is a postreplicative modification that occurs exclusively at the C5 position of cytosine residues (5mC) and predominantly in the context of CpG dinucleotides in vertebrate cells. Here, three major DNA methyltransferases (Dnmt1, 3a, and 3b) establish specific DNA methylation patterns during differentiation and maintain them over many cell division cycles. CpG methylation is recognized by at least three protein families that in turn recruit histone modifying and chromatin remodeling enzymes and thus translate DNA methylation into repressive chromatin structures. By now a multitude of histone modifications have been linked in various ways with DNA methylation. We will discuss some of the basic connections and the emerging complexity of these regulatory networks. J. Cell. Biochem. 108: 43–51, 2009. © 2009 Wiley‐Liss, Inc.
The cell adhesion nectin‐like molecules (Necl) 1 and 4 suppress the growth and tumorigenic ability of colon cancer cells
Authors: Raveh Shani , Gavert Nancy , Spiegel Ivo , Ben‐Ze'ev Avri 
Published: June 2009

AbstractA key step in human colon cancer development includes the hyperactivation of Wnt/β‐catenin signaling and the induction of β‐catenin‐TCF target genes that participate in colon cancer progression. Recent studies identified members of the immunoglobulin‐like cell adhesion molecules (IgCAM) of the L1CAM family (L1 and Nr‐CAM) as targets of β‐catenin‐TCF signaling in colon cancer cells. L1 was detected at the invasive front of colon cancer tissue and confers metastasis when overexpressed in cells. In contrast to L1, we did not detect in colon cancer cells significant levels of another IgCAM family of molecules, the nectin‐like (Necl) receptors Necl1 and Necl4, while Necl4 was previously found in the normal small intestine and colon tissues. We studied the properties of colon cancer cells in which Necl4 and Necl1 were expressed either alone, or in combination, and found that such cells display a wide range of properties associated with tumor suppression. Expression of both Necl1 and Necl4 was the most efficient in suppressing the tumorigenicity of colon cancer cells. This was associated with enhanced rates of apoptosis and change in several apoptosis‐related markers. In contrast to its capacity to suppress tumorigenesis, Necl4 was unable to affect the highly malignant and metastatic capacities of colon cancer cells in which L1 was overexpressed. Our results suggest that various IgCAM receptor families play different roles in affecting the tumorigenic function of the same cells, and that Necl1 and Necl4 can fulfill a tumor suppressive role. J. Cell. Biochem. 108: 326–336, 2009. © 2009 Wiley‐Liss, Inc.