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U2OS cells lacking Chk1 undergo aberrant mitosis and fail to activate the spindle checkpointEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Chk1 is a conserved protein kinase originally identified in fission yeast, required to delay entry of cells with damaged or unreplicated DNA into mitosis. The requirement of Chk1 for both S and G2/M checkpoints has been elucidated while only few studies have connected Chk1 to the mitotic spindle checkpoint. We used a small interference RNA strategy to investigate the role of Chk1 in unstressed conditions. Chk1 depletion in U2OS human osteosarcoma cells inhibited cell proliferation and raised the percentage of cells with a 4N DNA content, which correlated with accumulation of giant polynucleated cells morphologically distin...
Source: Journal of Cellular and Molecular Medicine - September 22, 2009 Category: Molecular Biology Authors: Laura Carrassa, Yolanda Sanchez, Eugenio Erba, Giovanna Damia Tags: ARTICLES Source Type: journals

Identification of pY19-caveolin-2 as a positive regulator of insulin-stimulated actin cytoskeleton-dependent mitogenesisEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Mitogenic regulation by caveolin-2 in response to insulin was investigated. Insulin triggered phosphorylation of caveolin-2 on tyrosine 19. Insulin increased the interaction between pY19-caveolin-2 and phospho-ERK, and that interaction was inhibited by a MEK inhibitor U0126. Insulin-induced interaction of caveolin-2 with phospho-ERK was prevented when tyrosine 19 is mutated to alanine. Insulin relocalized phospho-ERK and pY19-caveolin-2 to the nucleus and their nuclear co-localization was impaired by U0126. Down-regulation of caveolin-2 by caveolin-2 siRNA arrested the insulin-induced nuclear localization of ERK with no ch...
Source: Journal of Cellular and Molecular Medicine - September 22, 2009 Category: Molecular Biology Authors: Hayeong Kwon, Kyuho Jeong, Yunbae Pak Tags: ARTICLES Source Type: journals

Introduction to the tumour microenvironment Review SeriesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
(Source: Journal of Cellular and Molecular Medicine)
Source: Journal of Cellular and Molecular Medicine - July 31, 2009 Category: Molecular Biology Authors: Jack Lawler Tags: REVIEWS Source Type: journals

Translating tissue engineering technology platforms into cancer researchEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Conclusion Technology platforms originally developed for tissue engineering applications produce valuable models that mimic three-dimensional (3D) tissue organization and function to enhance the understanding of cell/tissue function under normal and pathological situations. These models show that when replicating physiological and pathological conditions as closely as possible investigators are allowed to probe the basic mechanisms of morphogenesis, differentiation and cancer. Significant efforts investigating angiogenetic processes and factors in tumorigenesis are currently undertaken to establish ways of targeting angiog...
Source: Journal of Cellular and Molecular Medicine - July 19, 2009 Category: Molecular Biology Authors: Dietmar W. Hutmacher, Raymund E. Horch, Daniela Loessner, Simone Rizzi, Shirly Sieh, Johannes C. Reichert, Judith A. Clements, Justus P. Beier, Andreas Arkudas, Oliver Bleiziffer, Ulrich Kneser Tags: REVIEWS Source Type: journals

Quantitative proteomic analysis of the cerebrospinal fluid of patients with multiple sclerosisEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The diagnosis of multiple sclerosis (MS) is challenging for the lack of a specific diagnostic test. Recent researches in quantitative proteomics, however, offer new opportunities for biomarker discovery and the study of disease pathogenesis. To find more potential protein biomarkers, we used two technologies, 2-dimensional fluorescence difference in-gel electrophoresis (2D-DIGE), followed by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) and ultra-performance liquid chromato-graph coupled with quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS), to quantitatively analyse...
Source: Journal of Cellular and Molecular Medicine - July 6, 2009 Category: Molecular Biology Authors: Shilian Liu, Shumei Bai, Zhaoyu Qin, Yinrong Yang, Yazhou Cui, Yanjiang Qin Tags: ARTICLES Source Type: journals

PKR, the double stranded RNA-dependent protein kinase as a critical target in Alzheimer's diseaseEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Conclusion and perspectives Amyloid [beta]-peptide (A[beta]) deposits and neurofibrillary tangles are key hallmarks in Alzheimer's disease (AD). A[beta] stimulates many signal transducers involved in the neuronal death. However, many mechanisms remain to be elucidated because no definitive therapy of AD exists. Some studies have focused on the control of translation which involves eIF2 and eIF4E, main eukaryotic factors of initiation. The availability of these factors depends on the activation of the double-stranded RNA-dependent protein kinase (PKR) and the mammalian target of rapamycin (mTOR), respectively. mTOR positive...
Source: Journal of Cellular and Molecular Medicine - July 6, 2009 Category: Molecular Biology Authors: Milena Morel, Julien Couturier, Claire Lafay-Chebassier, Marc Paccalin, Guylène Page Tags: REVIEWS Source Type: journals

Diabetes- and angiotensin II-induced cardiac endoplasmic reticulum stress and cell death: metallothionein protectionEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We have shown cardiac protection by metallothionein (MT) in the development of diabetic cardiomyopathy (DCM) via suppression of cardiac cell death in cardiac-specific MT-overexpressing transgenic (MT-TG) mice. The present study was undertaken to define whether diabetes can induce cardiac endoplasmic reticulum (ER) stress and whether MT can prevent cardiac cell death via attenuating ER stress. Diabetes was induced by streptozotocin in both MT-TG and wild-type (WT) mice. Two weeks, and 2 and 5 months after diabetes onset, cardiac ER stress was detected by expression of ER chaperones, and apoptosis was detected by CCAAT/enhan...
Source: Journal of Cellular and Molecular Medicine - July 5, 2009 Category: Molecular Biology Authors: Jiancheng Xu, Guanjun Wang, Yuehui Wang, Qiuju Liu, Wei Xu, Yi Tan, Lu Cai Tags: REVIEWS Source Type: journals

The immune boundaries for stem cell based therapies: problems and prospective solutionsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Conclusions Stem cells have fascinated the scientific and clinical communities for over a century. Despite the controversy that surrounds this field, it is clear that stem cells have the potential to revolutionize medicine. However, a number of significant hurdles still stand in the way of the realization of this potential. Chiefly among these are safety concerns, differentiation efficiency and overcoming immune rejection. Here we review current progress made in this field to optimize the safe use of stem cells with particular emphasis on prospective interventions to deal with challenges generated by immune rejection. (Sou...
Source: Journal of Cellular and Molecular Medicine - July 5, 2009 Category: Molecular Biology Authors: Hmadcha Abdelkrim, Domínguez-Bendala Juan, Wakeman Jane, Arredouani Mohamed, Soria Bernat Tags: REVIEWS Source Type: journals

Image-guided tissue engineeringEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Conclusions Replication of anatomic shape is a significant challenge in developing implants for regenerative medicine. This has lead to significant interest in using medical imaging techniques such as magnetic resonance imaging and computed tomography to design tissue engineered constructs. Implementation of medical imaging and computer aided design in combination with technologies for rapid prototyping of living implants enables the generation of highly reproducible constructs with spatial resolution up to 25 [mu]m. In this paper, we review the medical imaging modalities available and a paradigm for choosing a particular ...
Source: Journal of Cellular and Molecular Medicine - July 5, 2009 Category: Molecular Biology Authors: Jeffrey J. Ballyns, Lawrence J. Bonassar Tags: REVIEWS Source Type: journals

Lymphangiogenesis and cancer metastasisEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This article reviews the current understanding of lymphangiogenesis in cancer anti-lymphangiogenic strategies for prevention and therapy of metastatic disease, quantification of lymphangiogenesis for the prognosis and diagnosis of metastasis and in vivo imaging technologies for the assessment of lymphatic vessels, drainage and lymph nodes. (Source: Journal of Cellular and Molecular Medicine)
Source: Journal of Cellular and Molecular Medicine - July 5, 2009 Category: Molecular Biology Authors: Viviane Mumprecht, Michael Detmar Tags: REVIEWS Source Type: journals

Interplay among enteric neurons, interstitial cells of Cajal, resident and not resident connective tissue cellsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
(Source: Journal of Cellular and Molecular Medicine)
Source: Journal of Cellular and Molecular Medicine - June 30, 2009 Category: Molecular Biology Authors: Maria-Simonetta Faussone-Pellegrini Tags: REVIEWS Source Type: journals

Avoiding lentiviral transduction culture induced MSC senescenceEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
(Source: Journal of Cellular and Molecular Medicine)
Source: Journal of Cellular and Molecular Medicine - June 30, 2009 Category: Molecular Biology Authors: Yung-Wei Pan, Peter Kurre Tags: Letters to the Editor Source Type: journals

Nuclear lamins: key regulators of nuclear structure and activitiesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The lamin molecule Domain organization of lamins Lamins are divided to type A and type B Post-translational processing of lamin molecules Lamin molecules in evolution The supramolecular assembly of lamins From lamin monomer to lamin dimer From dimers to filaments The roles of the different domains in the assembly of lamins Laminopathic mutations affect lamin filament assembly Lamin assembly in vivo Lamin-binding proteins Lamins, chromatin and epigenesis Lamin binding to DNA Lamin binding to chromatin Lamins affect chromatin organization and epigenesis Lamins are involved in many nuclear functions Lamins determine the shape...
Source: Journal of Cellular and Molecular Medicine - June 30, 2009 Category: Molecular Biology Authors: Miron Prokocimer, Maya Davidovich, Malka Nissim-Rafinia, Naama Wiesel-Motiuk, Daniel Z. Bar, Rachel Barkan, Eran Meshorer, Yosef Gruenbaum Tags: REVIEWS Source Type: journals

Fibroblast growth factor receptor-1 phosphorylation requirement for cardiomyocyte differentiation in murine embryonic stem cellsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In conclusion, our results suggest that, although FGFR1 kinase activity is necessary for both cardiac and haematopoietic lineage maturation in mESC, phosphorylation of Y463 in the intracellular domain of the receptor is a specific requirement for cardiomyocyte differentiation. (Source: Journal of Cellular and Molecular Medicine)
Source: Journal of Cellular and Molecular Medicine - June 21, 2009 Category: Molecular Biology Authors: Roberto Ronca, Laura Gualandi, Elisabetta Crescini, Stefano Calza, Marco Presta, Patrizia Dell'Era Tags: REVIEWS Source Type: journals

Leukocyte – endothelial interactions in inflammationEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Conclusions At sites of inflammation, infection or vascular injury local proinflammatory or pathogen-derived stimuli render the luminal vascular endothelial surface attractive for leukocytes. This innate immunity response consists of a well-defined and regulated multi-step cascade involving consecutive steps of adhesive interactions between the leukocytes and the endothelium. During the initial contact with the activated endothelium leukocytes roll along the endothelium via a loose bond which is mediated by selectins. Subsequently, leukocytes are activated by chemokines presented on the luminal endothelial surface, which r...
Source: Journal of Cellular and Molecular Medicine - June 15, 2009 Category: Molecular Biology Authors: Harald F. Langer, Triantafyllos Chavakis Tags: REVIEWS Source Type: journals

Development of enteric neuron diversityEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Conclusions The mature enteric nervous system (ENS) is composed of many different neuron subtypes and enteric glia, which all arise from the neural crest. How this diversity is generated from neural crest-derived cells is a central question in neurogastroenterology, as defects in these processes are likely to underlie some paediatric motility disorders. Here we review the developmental appearance (the earliest age at which expression of specific markers can be localized) and birthdates (the age at which precursors exit the cell cycle) of different enteric neuron subtypes, and their projections to some targets. We then focu...
Source: Journal of Cellular and Molecular Medicine - June 15, 2009 Category: Molecular Biology Authors: Marlene M. Hao, Heather M. Young Tags: REVIEWS Source Type: journals

CorrigendumEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
(Source: Journal of Cellular and Molecular Medicine)
Source: Journal of Cellular and Molecular Medicine - June 11, 2009 Category: Molecular Biology Tags: Corrigendum Source Type: journals

Immunomodulatory and anti-inflammatory effects of chondroitin sulphateEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Conclusions Chondroitin sulphate (CS) is a natural glycosaminoglycan present in the extracellular matrix and is formed by the 1[ndash]3 linkage of D-glucuronic acid to N-acetylgalactosamine. In chondrocytes, CS diminishes interleukin-1 p (IL-1p)-induced increases in p38 mitogen-activated protein kinase (p38MAPK) and signal-regulated kinase 1/2 (Erk1/2) phosphorylation, and decreases nuclear factor-KB (NF-kB) nuclear translocation and as a consequence, reduces the formation of pro-inflammatory cytokines, IL-1 p and TNF-a, and pro-inflammatory enzymes, such as phospholipase A2 (PLA2), cyclooxygenase 2 (COX-2) and nitric oxid...
Source: Journal of Cellular and Molecular Medicine - June 10, 2009 Category: Molecular Biology Authors: Patrick du Souich, Antonio G. García, Josep Vergés, Eulàlia Montell Tags: REVIEWS Source Type: journals

Epigenetic therapy in myeloproliferative neoplasms: evidence and perspectivesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Conclusions The classic Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs), which include polycythaemia vera, essential thrombocythaemia and primary myelofibrosis, originate from a stem cell-derived clonal myeloproliferation that manifests itself with variable haematopoietic cell lineage involvement; they are characterized by a high degree of similarities and the chance to transform each to the other and to evolve into acute leukaemia. Their molecular pathogenesis has been associated with recurrent acquired mutations in janus kinase 2 (JAK2) and myeloproliferative leukemia virus oncogene (MPL). These disc...
Source: Journal of Cellular and Molecular Medicine - June 10, 2009 Category: Molecular Biology Authors: Alessandro M. Vannucchi, Paola Guglielmelli, Alessandro Rambaldi, Costanza Bogani, Tiziano Barbui Tags: REVIEWS Source Type: journals

Deficiency in TLR4 signal transduction ameliorates cardiac injury and cardiomyocyte contractile dysfunction during ischemiaEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Toll-like receptor 4 (TLR4), a proximal signalling receptor in innate immune responses to lipopolysaccharide of gram-negative pathogens, is expressed in the heart. Accumulating evidence have consolidated the notion that TLR4 plays an essential role in the pathogenesis of cardiac dysfunction. However, the molecular mechanisms of TLR4 responsible for ischemia-induced cardiac dysfunction remain unclear. To address the signalling mechanisms of TLR4-deficiency cardioprotection against ischemic injury, in vivo regional ischemia was induced by occlusion of the left anterior descending coronary artery in wild-type (WT) C3H/HeN and...
Source: Journal of Cellular and Molecular Medicine - June 4, 2009 Category: Molecular Biology Authors: Peng Zhao, Jingying Wang, Leilei He, Heng Ma, Xiaoyu Zhang, Xinglei Zhu, E. Kurt Dolence, Jun Ren, Ji Li Tags: REVIEWS Source Type: journals

The mitochondrial death pathway: a promising therapeutic target in diseasesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Conclusion and future directions The mitochondrial pathway to apoptosis is a major pathway of physiological cell death in vertebrates. The mitochondrial cell death pathway commences when apoptogenic molecules present between the outer and inner mitochondrial membranes are released into the cytosol by mitochondrial outer membrane permeabilization (MOMP). BCL-2 family members are the sentinels of MOMP in the mitochondrial apoptotic pathway; the pro-apoptotic B cell lymphoma (BCL)-2 proteins, BCL-2 associated x protein and BCL-2 antagonist killer 1 induce MOMP whereas the anti-apoptotic BCL-2 proteins, BCL-2, BCL-xl and myelo...
Source: Journal of Cellular and Molecular Medicine - May 31, 2009 Category: Molecular Biology Authors: Sanjeev Gupta, George E.N. Kass, Eva Szegezdi, Bertrand Joseph Tags: REVIEWS Source Type: journals

Kit K641E oncogene up-regulates Sprouty homolog 4 and Trophoblast glycoprotein in interstitial cells of Cajal in a murine model of gastrointestinal stromal tumoursEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Gastrointestinal stromal tumours (GIST) are thought to derive from the interstitial cells of Cajal (ICC) or an ICC precursor. Oncogenic mutations of the receptor tyrosine kinase KIT are present in most GIST. KIT K642E was originally identified in sporadic GIST and later found in the germ line of a familial GIST cohort. A mouse model harbouring a germline Kit K641E mutant was created to model familial GIST. The expression profile was investigated in the gastric antrum of the KitK641E murine GIST model by microarray, quantitative PCR and immunofluorescence. Gja1/Cx43, Gpc6, Gpr133, Pacrg, Pde3a, Prkar2b, Prkcq/Pkce, Rasd2, S...
Source: Journal of Cellular and Molecular Medicine - May 18, 2009 Category: Molecular Biology Authors: Petra Gromova, Sebastian Ralea, Anne Lefort, Frédérick Libert, Brian P Rubin, Christophe Erneux, Jean-Marie Vanderwinden Tags: ARTICLES Source Type: journals

CX3CL1/fractalkine shedding by human hepatic stellate cells: contribution to chronic inflammation in the liverEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Chemokines are the inflammatory mediators that modulate liver fibrosis, a common feature of chronic inflammatory liver diseases. CX3CL1/fractalkine is a membrane-associated chemokine that requires step processing for chemotactic activity and has been recently implicated in liver disease. Here, we investigated the potential shedding activities involved in the release of the soluble chemotactic peptides from CX3CL1 in the injured liver. We showed an increased expression of the sheddases ADAM10 and ADAM17 in patients with chronic liver diseases that was associated with the severity of liver fibrosis. We demonstrated that hepa...
Source: Journal of Cellular and Molecular Medicine - May 10, 2009 Category: Molecular Biology Authors: Katia Bourd-Boittin, Laetitia Basset, Dominique Bonnier, Annie L'Helgoualc'h, Michel Samson, Nathalie Théret Tags: ARTICLES Source Type: journals

The rat as an animal model of Alzheimer's diseaseEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Introduction The laboratory rat Rat models of cholinergic-clysfunction A[beta]-based models of AD Transgenic rats The TgAPPswe rat The UKUR25 rat The Tg6590 rat The triple transgenic rat The APP21 and APP31 transgenic rats The AD-tau rat Transgenic rats [ndash] summary Virally induced models of AD Concluding remarks As a disease model, the laboratory rat has contributed enormously to neuroscience research over the years. It has also been a popular animal model for Alzheimer's disease but its popularity has diminished during the last decade, as techniques for genetic manipulation in rats have lagged behind that of mice. In ...
Source: Journal of Cellular and Molecular Medicine - May 10, 2009 Category: Molecular Biology Authors: Eirikur Benedikz, Ewa Kloskowska, Bengt Winblad Tags: REVIEWS Source Type: journals

Three-dimensional electron microscopic reconstruction of intracellular organellar arrangements in vascular smooth muscle – further evidence of nanospaces and contactsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The sarcoplasmic reticulum (SR) of smooth muscle is crucial for appropriate regulation of Ca2+ signalling. In visceral and vascular smooth muscles the SR is known to periodically lie in close register, within a few nanometres, to the plasma membrane. Recent work has focussed on reconstructions of the ultrastructural arrangement of this so-called peripheral SR that may be important for the genesis of phenomena such as Ca2+ sparks. Here, we turn our attention to vascular smooth muscle and explore the 3-dimensional (3D) ultrastructural positioning of SR found deeper in the cell that is involved in the propagation of Ca2+ wave...
Source: Journal of Cellular and Molecular Medicine - May 3, 2009 Category: Molecular Biology Authors: Wing Chiu Tong, Michele Sweeney, Carolyn J. P. Jones, Henggui Zhang, Stephen C. O'Neill, Ian Prior, Michael J. Taggart Tags: IMAGES IN CELLULAR/MOLECULAR MEDICINE Source Type: journals

Cartilage repair: past and future – lessons for regenerative medicineEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Conclusion and future directions Since the first cell therapeutic study to repair articular cartilage defects in the knee in 1994, several clinical studies have been reported. An overview of the results of clinical studies did not conclusively show improvement over conventional methods, mainly because few studies reach level I of evidence for effects on middle or long term. However, these explorative trials have provided valuable information about study design, mechanisms of repair and clinical outcome and have revealed that much is still unknown and further improvements are required. Furthermore, cellular and molecular st...
Source: Journal of Cellular and Molecular Medicine - April 30, 2009 Category: Molecular Biology Authors: Gerjo J. V. M. van Osch, Mats Brittberg, James E. Dennis, Yvonne M. Bastiaansen-Jenniskens, Reinhold G. Erben, Yrjö T. Konttinen, Frank P. Luyten Tags: REVIEWS Source Type: journals

Cardiac renewing: interstitial Cajal-like cells nurse cardiomyocyte progenitors in epicardial stem cell nichesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Recent studies suggested that various cell lineages exist within the subepicardium and we supposed that this area could host cardiac stem cell niches (CSCNs). Using transmission electron microscopy, we have found at least 10 types of cells coexisting in the subepicardium of normal adult mice: adipocytes, fibroblasts, Schwann cells and nerve fibres, isolated smooth muscle cells, mast cells, macrophages, lymphocytes, interstitial Cajal-like cells (ICLCs) and cardiomyocytes progenitors (CMPs). The latter cells, sited in the area of origin of coronary arteries and aorta, showed typical features of either very immature or devel...
Source: Journal of Cellular and Molecular Medicine - April 19, 2009 Category: Molecular Biology Authors: L. M. Popescu, Mihaela Gherghiceanu, C. G. Manole, Maria Simonetta Faussone-Pellegrini Tags: ARTICLES Source Type: journals

Metabolic modulation and cellular therapy of cardiac dysfunction and failureEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Introduction Metabolic modulation Metabolism in the normal heart Substrate uptake and oxidation Oxidative phosphorylation ATP transport and utilization Metabolism in heart failure Changes in substrate utilization Effects on oxidative phosphorylation Changes in ATP transport and utilization Medications that influence metabolism in heart failure (Table 2) Cell therapy Skeletal muscle myoblasts Human embryonic stem cells Bone marrow derived adult stem cells Haematopoietic stem cells Mesenchymal stem cells (MSC) Endothelial progenitor cells (EPCs) Cardiac stem cells Mechanisms of stem cell mediated myocardial regeneration Clin...
Source: Journal of Cellular and Molecular Medicine - April 19, 2009 Category: Molecular Biology Authors: Diana Revenco, James P. Morgan Tags: REVIEWS Source Type: journals

Endocytosis via caveolae: alternative pathway with distinct cellular compartments to avoid lysosomal degradation?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Conclusion Endocytosis [ndash] the uptake of extracellular ligands, soluble molecules, protein and lipids from the extracellular surface [ndash] is a vital process, comprising multiple mechanisms, including phagocytosis, macropinocytosis, clathrin-dependent and clathrin-independent uptake such as caveolae-mediated and non-caveolar raft-dependent endocytosis. The best-studied endocytotic pathway for internalizing both bulk membrane and specific proteins is the clathrin-mediated endocytosis. Although many papers were published about the caveolar endocytosis, it is still not known whether it represents an alternative pathway ...
Source: Journal of Cellular and Molecular Medicine - March 27, 2009 Category: Molecular Biology Authors: Anna L. Kiss, Erzsébet Botos Tags: REVIEWS Source Type: journals

Apoptosis pathways and their therapeutic exploitation in pancreatic cancerEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Conclusions Resistance to apoptosis (programmed cell death) is a characteristic feature of human malignancies including pancreatic cancer, which is one of the leading causes of cancer deaths in the western world. Defects in this intrinsic cell death program can contribute to the multistep process of tumorigenesis, because too little cell death can disturb tissue homeostasis. Further, blockade of apoptosis pathways can cause treatment failure, because intact apoptosis signalling cascades largely mediate therapy-induced cytotoxicity. The elucidation of apoptosis pathways in pancreatic carcinoma over the last decade has resul...
Source: Journal of Cellular and Molecular Medicine - March 27, 2009 Category: Molecular Biology Authors: Simone Fulda Tags: REVIEWS Source Type: journals

Cellular/intramuscular myxoma and grade I myxofibrosarcoma are characterized by distinct genetic alterations and specific composition of their extracellular matrixEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Cellular myxoma and grade I myxofibrosarcoma are mesenchymal tumours that are characterized by their abundant myxoid extracellular matrix (ECM). Despite their histological overlap, they differ clinically. Diagnosis is therefore difficult though important. We investigated their (cyto) genetics and ECM. GNAS1-activating mutations have been described in intramuscular myxoma, and lead to downstream activation of cFos. KRAS and TP53 mutations are commonly involved in sarcomagenesis whereby KRAS subsequently activates c-Fos. A well-documented series of intramuscular myxoma (three typical cases and seven cases of the more challen...
Source: Journal of Cellular and Molecular Medicine - March 13, 2009 Category: Molecular Biology Authors: Stefan M. Willems, Alex B. Mohseny, Crina Balog, Raj Sewrajsing, Inge H. Briaire-de Bruijn, Jeroen Knijnenburg, Anne-Marie Cleton-Jansen, Raf Sciot, Christopher D. M. Fletcher, André M. Deelder, Karoly Szuhai, Paul J. Hensbergen, Pancras C. W. Hogendoorn Tags: ARTICLES Source Type: journals

Healthy human salivary glands contain a DHEA-sulphate processing intracrine machinery, which is deranged in primary Sjögren's syndromeEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Sjögren's syndrome (SS) patients have low salivary dehydroepiandrosterone (DHEA) and androgen biomarker levels, but high salivary oestrogen levels. The hypothesis was that the healthy glands contain DHEA-sulphate processing intracrine machinery; the local androgen/oestrogen imbalance suggests that this is disarranged in SS. Indirect immunofluorescence and quantitative real-time PCR (qRT-PCR) of steroid sulphatase, sulfotransferase, 3[beta]- and 17[beta]-hydroxysteroid dehydrogenases (3[beta]- and 17[beta]-HSD), 5[alpha]-reductase and aromatase were performed for labial salivary glands of healthy controls and persons with ...
Source: Journal of Cellular and Molecular Medicine - February 27, 2009 Category: Molecular Biology Authors: Michelle Spaan, Pauliina Porola, Mikael Laine, Blaz Rozman, Masayuki Azuma, Yrjö T. Konttinen Tags: ARTICLES Source Type: journals

Are haemophiliacs protected against cancer development? Prospective controlled studies are neededEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
(Source: Journal of Cellular and Molecular Medicine)
Source: Journal of Cellular and Molecular Medicine - February 18, 2009 Category: Molecular Biology Authors: Massimo Franchini, Giuseppe Lippi Tags: Letters to the Editor Source Type: journals

Regeneration of bone and periodontal ligament induced by recombinant amelogenin after periodontitisEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Regeneration of mineralized tissues affected by chronic diseases comprises a major scientific and clinical challenge. Periodontitis, one such prevalent disease, involves destruction of the tooth-supporting tissues, alveolar bone, periodontal-ligament and cementum, often leading to tooth loss. In 1997, it became clear that, in addition to their function in enamel formation, the hydrophobic ectodermal enamel matrix proteins (EMPs) play a role in the regeneration of these periodontal tissues. The epithelial EMPs are a heterogeneous mixture of polypeptides encoded by several genes. It was not clear, however, which of these man...
Source: Journal of Cellular and Molecular Medicine - February 18, 2009 Category: Molecular Biology Authors: Amir Haze, Angela L. Taylor, Stefan Haegewald, Yoav Leiser, Boaz Shay, Eli Rosenfeld, Yael Gruenbaum-Cohen, Leah Dafni, Bernd Zimmermann, Kristiina Heikinheimo, Carolyn W. Gibson, Larry W. Fisher, Marian F. Young, Anat Blumenfeld, Jean P. Bernimoulin, Dan Tags: ARTICLES Source Type: journals

The R439C mutation in LMNA causes lamin oligomerization and susceptibility to oxidative stressEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Dunnigan-type familial partial lipodystrophy (FPLD) is a laminopathy characterized by an aberrant fat distribution and a metabolic syndrome for which oxidative stress has recently been suggested as one of the disease-causing mechanisms. In a family affected with FPLD, we identified a heterozygous missense mutation c.1315C>T in the LMNA gene leading to the p.R439C substitution. Cultured patient fibroblasts do not show any prelamin A accumulation and reveal honeycomb-like lamin A/C formations in a significant percentage of nuclei. The mutation affects a region in the C-terminal globular domain of lamins A and C, different fr...
Source: Journal of Cellular and Molecular Medicine - February 11, 2009 Category: Molecular Biology Authors: Valerie L.R.M. Verstraeten, Sandrine Caputo, Maurice A.M. van Steensel, Isabelle Duband-Goulet, Sophie Zinn-Justin, Miriam Kamps, Helma J.H. Kuijpers, Cecilia Östlund, Howard J. Worman, Jacob J. Briedé, Caroline Le Dour, Carlo L.M. Marcelis, Michel van Tags: ARTICLES Source Type: journals

Cellular repressor of E1A-stimulated genes attenuates cardiac hypertrophy and fibrosisEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Cellular repressor of E1A-stimulated genes (CREG) is a secreted glycoprotein of 220 amino acids. It has been proposed that CREG acts as a ligand that enhances differentiation and/or reduces cell proliferation. CREG has been shown previously to attenuate cardiac hypertrophy in vitro. However, such a role has not been determined in vivo. In the present study, we tested the hypothesis that overexpression of CREG in the murine heart would protect against cardiac hypertrophy and fibrosis in vivo. The effects of constitutive human CREG expression on cardiac hypertrophy were investigated using both in vitro and in vivo models. Ca...
Source: Journal of Cellular and Molecular Medicine - December 24, 2008 Category: Molecular Biology Authors: Zhouyan Bian, Jun Cai, Di-fei Shen, Li Chen, Ling Yan, Qizhu Tang, Hongliang Li Tags: ARTICLES Source Type: journals

Pharmacological induction of vascular extracellular superoxide dismutase expression in vivoEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Pentaerythritol tetranitrate (PETN) treatment reduces progression of atherosclerosis and endothelial dysfunction and decreases oxidation of low-density lipoprotein (LDL) in rabbits. These effects are associated with decreased vascular superoxide production, but the underlying molecular mechanisms remain unknown. Previous studies demonstrated that endogenous nitric oxide could regulate the expression of extracellular superoxide dismutase (ecSOD) in conductance vessels in vivo. We investigated the effect of PETN and overexpression of endothelial nitric oxide synthase (eNOS++) on the expression and activity of ecSOD. C57BL/6 ...
Source: Journal of Cellular and Molecular Medicine - December 24, 2008 Category: Molecular Biology Authors: Marc Oppermann, Vera Balz, Volker Adams, Vu Thao-Vi Dao, Murat Bas, Tatsiana Suvorava, Georg Kojda Tags: ARTICLES Source Type: journals

Expression of microRNAs in diffuse large B cell lymphoma is associated with immunophenotype, survival and transformation from follicular lymphomaEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
MicroRNAs are naturally occurring small RNA species that regulate gene expression and are frequently abnormally expressed in cancers. However, the role of microRNAs in lymphoma is poorly understood. Therefore, we undertook a comprehensive study of microRNA expression in two of the most common lymphomas: diffuse large B-cell lymphoma (DLBCL) (n= 80) and follicular lymphoma (FCL) (n= 18) using microarrays containing probes for 464 human microRNAs. Unsupervised cluster analysis revealed distinct expression patterns between these two lymphomas and specific microRNA signatures (including members of the miR-17[ndash]92 cluster) ...
Source: Journal of Cellular and Molecular Medicine - December 24, 2008 Category: Molecular Biology Authors: Charles H. Lawrie, Jianxiang Chi, Stephen Taylor, Daniela Tramonti, Erica Ballabio, Stefano Palazzo, Nigel J. Saunders, Francesco Pezzella, Jacqueline Boultwood, James S. Wainscoat, Christian S. R. Hatton Tags: ARTICLES Source Type: journals

In GERD patients, mucosal repair associated genes are upregulated in non-inflamed oesophageal epitheliumEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Previous studies addressing the effects of acid reflux and PPI therapy on gene expression in oesophageal epithelium concentrated on inflamed tissue. We aimed to determine changes in gene expression in non-inflamed oesophageal epithelium of GERD patients. Therefore, we included 20 GERD patients with pathological total 24-hr acid exposure of 6[ndash]12% and SAP [ge] 95%. Ten patients discontinued PPI treatment (PPI-), 10 took pantoprazole 40 mg bid (PPI+). Ten age/sex-matched healthy controls were recruited. Biopsies were taken from non-inflamed mucosa 6 cm and 16 cm proximal to the squamocolumnar junction (SCJ). Gene expres...
Source: Journal of Cellular and Molecular Medicine - December 24, 2008 Category: Molecular Biology Authors: D. R. de Vries, J. J. M. Ter Linde, M. A. van Herwaarden, M. P. Schwartz, P. Shephard, M. M. Geng, A. J. P. M. Smout, M. Samsom Tags: ARTICLES Source Type: journals

Crocetin protects against cardiac hypertrophy by blocking MEK-ERK1/2 signalling pathwayEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Oxidative stress plays a critical role in the progression of pathological cardiac hypertrophy and heart failure. Because crocetin represses oxidative stress in vitro and in vivo, we have suggested that crocetin would repress cardiac hypertrophy by targeting oxidative stress-dependent signalling. We tested this hypothesis using primary cultured cardiac myocytes and fibroblasts and one well-established animal model of cardiac hypertrophy. The results showed that crocetin (1[ndash]10 [mu]M) dose-dependently blocked cardiac hypertrophy induced by angiogensin II (Ang II; 1 [mu]M) in vitro. Our data further revealed that croceti...
Source: Journal of Cellular and Molecular Medicine - December 24, 2008 Category: Molecular Biology Authors: Jun Cai, Fang-Fang Yi, Zhou-Yan Bian, Di-Fei Shen, Long Yang, Ling Yan, Qi-Zhu Tang, Xin-Chun Yang, Hongliang Li Tags: ARTICLES Source Type: journals

Antagomir-mediated silencing of endothelial cell specific microRNA-126 impairs ischemia-induced angiogenesisEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
MicroRNAs are negative regulators of gene expression that play a key role in cell-type specific differentiation and modulation of cell function and have been proposed to be involved in neovascularization. Previously, using an extensive cloning and sequencing approach, we identified miR-126 to be specifically and highly expressed in human endothelial cells (EC). Here, we demonstrate EC-specific expression of miR-126 in capillaries and the larger vessels in vivo. We therefore explored the potential role of miR-126 in arteriogenesis and angiogenesis. Using miR-reporter constructs, we show that miR-126 is functionally active i...
Source: Journal of Cellular and Molecular Medicine - December 16, 2008 Category: Molecular Biology Authors: Coen van Solingen, Leonard Seghers, Roel Bijkerk, Jacques M.G.J. Duijs, Marko K. Roeten, Annemarie M. van Oeveren-Rietdijk, Hans J. Baelde, Matthieu Monge, Joost B. Vos, Hetty C. de Boer, Paul H.A. Quax, Ton J. Rabelink, Anton Jan van Zonneveld Tags: ARTICLES Source Type: journals

Measuring and monitoring apoptosis and drug toxicity in HIV patients by ligation-mediated polymerase chain reactionEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Apoptosis has a critical role in normal physiology while its dysregulation has causal links with certain pathologies. A biochemical hallmark of apoptosis, internucleosomal genomic DNA fragmentation, is detectable by ligation-mediated polymerase chain reaction (LM-PCR). Here we converted LM-PCR into a new apoptosis quantifier by dividing trace quantities of 600 bp apoptotic amplicons into those of a single copy house-keeping gene, generating the LM-PCR 'value'. Dynamic range was [sim]17-fold correlating with a [sim]200-fold difference in degree of apoptotic fragmentation. Inter- and intra-gel reliability were both excellent...
Source: Journal of Cellular and Molecular Medicine - December 16, 2008 Category: Molecular Biology Authors: David J. Hooker, Paul R. Gorry, Anne M. Ellett, Steven L. Wesselingh, Catherine L. Cherry Tags: ARTICLES Source Type: journals

Islet-like cell clusters occur naturally in human gall bladder and are retained in diabetic conditions†Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
(Source: Journal of Cellular and Molecular Medicine)
Source: Journal of Cellular and Molecular Medicine - November 3, 2008 Category: Molecular Biology Authors: Subhshri Sahu, Mugdha V. Joglekar, Ramesh Dumbre, Smruti M. Phadnis, David Tosh, Anandwardhan A. Hardikar Tags: IMAGES IN CELLULAR/MOLECULAR MEDICINE Source Type: journals

Targeting histone deacetylases for the treatment of diseaseEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Introduction HATs/HDACs and the pro-inflammatory environment HATs/HDACs and endoplasmic reticulum (ER) stress The potential role of histone deacetylase inhibitors in the treatment of cancer Non-small cell cancer (NSCLC) In vitro evidence for targeting HDACs in NSCLC Combinatorial therapies involving HDi in NSCLC Hepatocellular carcinoma (HCC) In vitro evidence for the use of HDi in liver cancer Combinatorial treatments involving HDi in hepatoma Potential role of histone deacetylase inhibitors in the treatment of diabetes Disease models, knockouts and assays Pancreatic islet protection using histone deacetylase inhibitors A...
Source: Journal of Cellular and Molecular Medicine - November 3, 2008 Category: Molecular Biology Authors: M. W. Lawless, S. Norris, K. J. O'Byrne, S. G. Gray Tags: REVIEWS Source Type: journals

Oncolytic virotherapy for advanced liver tumoursEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Introduction Pre-clinical studies Clinical studies Challenges for the use of virotherapy agents in liver tumour treatment Future directions Primary and metastatic neoplasms of the liver account for more than a million deaths per year worldwide. Despite decades of research, effective novel therapies for these cancers are urgently needed. Oncolytic virotherapeutics represent a novel class of pharmacophore that holds promise for the treatment of hepatic neoplasms. Cancer-specific replication is followed by oncolysis, virus spreading and infection of adjacent cancer cells. This process is then repeated. Virotherapeutics target...
Source: Journal of Cellular and Molecular Medicine - October 22, 2008 Category: Molecular Biology Authors: Ju-Fang Chang, Pei-Jer Chen, Daniel Y. Sze, Tony Reid, David Bartlett, David H. Kirn, Ta-Chiang Liu Tags: REVIEWS Source Type: journals

Signal transduction of MCP-1 expression induced by pancreatitis-associated ascitic fluid in pancreatic acinar cellsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In conclusion, acinar cells were activated by PAAF to produce MCP-1, mainly via NF-[kappa]B and STAT3 pathways. Both downstream pathways were targeted by Dx and NAC to repress the PAAF-mediated acinar MCP-1 up-regulation. (Source: Journal of Cellular and Molecular Medicine)
Source: Journal of Cellular and Molecular Medicine - October 12, 2008 Category: Molecular Biology Authors: Laura Ramudo, Sara Yubero, Manuel A. Manso, Secundino Vicente, Isabel De Dios Tags: ARTICLES Source Type: journals

The missing link between indoleamine 2,3-dioxygenase mediated antibacterial and immunoregulatory effectsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, we provide evidence that both tryptophan starvation and production of toxic tryptophan metabolites are involved in the immunoregulation mediated by IDO, whereas tryptophan starvation seems to be the only antibacterial effector mechanism. A long-studied controversy in the IDO research field is the seemingly contradictory effect of IDO in the defence against infectious diseases. On the one hand, IFN-[gamma]-induced IDO activity mediates an antimicrobial effect, while at the same time IDO inhibits T-cell proliferation and IFN[ndash][gamma] production. Here, we suggest that both effects, dependent on the thresho...
Source: Journal of Cellular and Molecular Medicine - October 12, 2008 Category: Molecular Biology Authors: Anika Müller, Kathrin Heseler, Silvia K. Schmidt, Katrin Spekker, Colin R. MacKenzie, Walter Däubener Tags: ARTICLES Source Type: journals

Reduced ligand affinity leads to an impaired function of the adenosine A2A receptor of human granulocytes in sepsisEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We report that lipopolysaccharide (LPS)-incubation of human PMN elicited the same increase in the half-maximal inhibitory concentration (IC50) of adenosine as observed in patients with septic shock. Coupling to adenylyl cyclase was impaired as well, as indicated by a decreased potency of adenosine to stimulate cyclic adenosine monophosphate (cAMP) accumulation. Ligand-binding studies conducted with native, LPS-stimulated PMN, and with PMN of sepsis patients revealed that, despite an increased adenosine A2A receptor (A2AR) expression, the receptor function declines due to a diminished ligand-binding affinity most likely cau...
Source: Journal of Cellular and Molecular Medicine - October 12, 2008 Category: Molecular Biology Authors: Simone Kreth, Ines Kaufmann, Carola Ledderose, Benjamin Luchting, Manfred Thiel Tags: ARTICLES Source Type: journals