Integrin alpha 10, CD44, PTEN, cadherin-11 and lactoferrin expressions are potential biomarkers for selecting patients in need of central nervous system prophylaxis in diffuse large B-cell lymphoma.

Central nervous system (CNS) relapse is a devastating complication that occurs in about 5% of diffuse large B-cell lymphoma (DLBCL) patients. Currently, there are no predictive biological markers. We wanted to study potential biomarkers of CNS tropism that play a role in adhesion, migration and/or in the regulation of inflammatory responses.

Human bone marrow mesenchymal stem cells induce collagen production and tongue cancer invasion.

Tumor microenvironment (TME) is an active player in carcinogenesis and changes in its composition modify cancer growth. Carcinoma-associated fibroblasts, bone marrow-derived multipotent mesenchymal stem cells (BMMSCs), and inflammatory cells can all affect the composition of TME leading to changes in proliferation, invasion and metastasis formation of carcinoma cells. In this study, we confirmed an interaction between BMMSCs and oral tongue squamous cell carcinoma (OTSCC) cells by analyzing the invasion progression and gene expression pattern.

Stress-specific responses of p21 expression: implication of transcript variant p21 alt-a in long-term hypoxia.

p21 (CDKN1A, Cip1, Waf1) is a cyclin-dependent kinase inhibitor capable of causing cell cycle arrest or promoting cell cycle transit as well as acting as a regulator of apoptosis. In this study, we analyzed the effects of various antemortem conditions on p21 protein level and expression profiles of known p21 transcript variants in human heart tissue. The selected death cause groups were: non-cardiac, hypothermia, acute ischemia, and chronic hypoxia.

Different responses in transformation of MDCK cells in 2D and 3D culture by v-Src as revealed by microarray techniques, RT-PCR and functional assays.

Differentiation and transformation of untransformed and ts-Src-transformed canine kidney MDCK cells in 2D and 3D environment were investigated using microarray technique, RT-PCR, confocal microscopy and functional assays. Activated Src induced epithelial-mesenchymal transition (EMT) in 2D environment followed by translocation of junctional proteins to the cytoplasm, without significant changes in protein expression. In 3D environment untransformed MDCK cells formed cell cysts with apical domain facing a lumen, E-cadherin delineating the lateral membranes, ZO-1 at tight junctions and caspase-3 in apoptotic cells captured within the lumen.

Genomic response to Wnt signalling is highly context-dependent--evidence from DNA microarray and chromatin immunoprecipitation screens of Wnt/TCF targets.

Wnt proteins are important regulators of embryonic development, and dysregulated Wnt signalling is involved in the oncogenesis of several human cancers. Our knowledge of the downstream target genes is limited, however. We used a chromatin immunoprecipitation-based assay to isolate and characterize the actual gene segments through which Wnt-activatable transcription factors, TCFs, regulate transcription and an Affymetrix microarray analysis to study the global transcriptional response to the Wnt3a ligand.

Adiponectin induced placental cell apoptosis could be mediated via the ADIPOR1-receptor in pre-eclampsia with IUGR.

Aims: Adiponectin and leptin are members of the adipocytokine family. Adiponectin promotes and leptin inhibits apoptosis and both are regulators of angiogenesis. Adipocytokines and their receptors are expressed in the placenta, and in the pre-eclamptic (PE) mother the serum levels of both are higher than in healthy ones.

A mutant collagen XIII alters intestinal expression of immune response genes and predisposes transgenic mice to develop B-cell lymphomas.

Epithelial cells of mucosal surfaces are critical for maintaining immune homeostasis by aiding in the discrimination of pathogenic and commensal microorganisms and modulating the activities of antigen-presenting cells and lymphocytes. Functional breakdowns resulting in chronic infection and inflammation are associated with the development of hematologic and solid neoplasms for which detailed pathogenetic mechanisms are poorly understood. Mice heterozygous for a transgene Col13a1(del) expressing a mutant collagen XIII developed clonal mature B-cell lineage lymphomas originating in mesenteric lymph nodes (MLN).

Norvaline is accumulated after a down-shift of oxygen in Escherichia coli W3110.

Background: Norvaline is an unusual non-proteinogenic branched-chain amino acid which has been of interest especially during the early enzymological studies on regulatory mutants of the branched-chain amino acid pathway in Serratia marcescens. Only recently norvaline and other modified amino acids of the branched-chain amino acid synthesis pathway got attention again when they were found to be incorporated in minor amounts in heterologous proteins with a high leucine or methionine content. Earlier experiments have convincingly shown that norvaline and norleucine are formed from pyruvate being an alternative substrate of alpha-isopropylmalate synthase, however so far norvaline accumulation was not shown to occur in non-recombinant strains of E.

Characterization of a novel Caenorhabditis elegans prolyl 4-hydroxylase with a unique substrate specificity and restricted expression in the pharynx and excretory duct.

Collagen prolyl 4-hydroxylases (C-P4Hs) have a critical role in collagen synthesis, since 4-hydroxyproline residues are necessary for folding of the triple-helical molecules. Vertebrate C-P4Hs are alpha(2)beta(2) tetramers in which the beta subunit is identical to protein-disulfide isomerase (PDI). Three isoforms of the catalytic alpha subunit, PHY-1, PHY-2, and PHY-3, have been characterized from Caenorhabditis elegans, PHY-1 and PHY-2 being responsible for the hydroxylation of cuticle collagens, whereas PHY-3 is predicted to be involved in collagen synthesis in early embryos.

The expression of myoglobin and ROR2 protein in Dupuytren's disease.

Background: Dupuytren's disease (DD) is a hand disease inherited as an autosomal dominant trait with variable penetrance, especially among populations of northern European ancestry. The etiology and pathophysiology of DD are not clear. The purpose of this study was to examine the gene expression profiles of palmar fascia of DD and healthy patients using microarray analysis to highlight the genes that might contribute to the pathogenesis of DD.

Effects of TGF-beta 1 on interleukin profile of human dental pulp and odontoblasts.

Transforming growth factor-beta 1 (TGF-beta1) is the most extensively studied growth factor in dentin-pulp complex, with pleiotropic effects on pulp response and healing. Our main objective was to analyze the expression profile of pulp tissue and odontoblasts, and the effects of TGF-beta1 on these profiles in cultured human pulp and odontoblasts with a specific interest in the anti- and pro-inflammatory cytokines. For that purpose, pulps and odontoblasts were cultured for different time periods, and microarray was performed to both cultured and native samples.

Altered expression of angiogenesis-related placental genes in pre-eclampsia associated with intrauterine growth restriction.

Aim: The normal endovascular invasion of trophoblast cells and spiral artery remodeling are impaired in pre-eclampsia. Neither the circulating factor secreted by the placenta nor the cause of the widespread endothelial dysfunction in pre-eclampsia has yet been identified. In an attempt to identify novel factors, we performed a gene expression profiling study of placental tissue from women with and without pre-eclampsia.

Iap2 is required for a sustained response in the Drosophila Imd pathway.

Fruit flies have effective immune response against Gram-negative bacteria. Upon infection, early JNK-signaling pathway mediated response is followed by the action of the Immune deficiency (Imd) signaling cascade, a Drosophila equivalent of mammalian TNF-receptor pathway, leading to the release of antimicrobial peptides. Recently, Tak1-binding protein 2 (Tab2) and Inhibitor of apoptosis 2 (Iap2) were identified as components of the Imd pathway.

Effects of phosphatidylethanol on mouse adipocyte differentiation and expression of stearoyl-CoA desaturase 1.

Background: Phosphatidylethanol (PEth) is an aberrant phospholipid formed in vivo only in the presence of ethanol. In circulation PEth is associated with lipoproteins and is transferred from one lipoprotein to another. Lipoprotein-associated PEth affects endothelial and smooth muscle cells of blood vessels, but its effects on other cell types have not been explored.

Characterization of androgen-regulated expression of CYP3A5 in human prostate.

Testosterone is needed for the growth and development of the prostate. Androgen deprivation therapy is used for the treatment of prostate cancer. CYP3A5 is a human drug-metabolizing cytochrome P450 enzyme that metabolizes testosterone to the inactive 6beta-hydroxylated metabolite.

Use of differentiating adult stem cells (marrow stromal cells) to identify new downstream target genes for transcription factors.

We developed a strategy for use of microarray data to rapidly identify new downstream targets of transcription factors known to drive differentiation by following the time courses of gene expression as a relatively homogeneous population of stem/progenitor cells are differentiated to multiple phenotypes. Microarray assays were used to follow the differentiation of human marrow stromal cells (MSCs) into chondrocytes or adipocytes in three different experimental conditions. The steps of the analysis were the following: (a) hierarchical clustering was used to define groups of similarly behaving genes in each experiment, (b) candidates for new downstream targets of transcription factors that drive differentiation were then identified as genes that were consistently co-expressed with known downstream target genes of the transcription factors, and (c) the list of candidate new target genes was refined by identifying genes whose signal intensities showed a highly significant linear regression with the signal intensities of the known targets in all the data sets.

The partial female to male sex reversal in Wnt-4-deficient females involves induced expression of testosterone biosynthetic genes and testosterone production, and depends on androgen action.

Wnt-4 signaling has been implicated in female development, because its absence leads to partial female to male sex reversal in the mouse. Instead of Mullerian ducts, Wnt-4-deficient females have Wolffian ducts, suggesting a role for androgens in maintaining this single-sex duct type in females. We demonstrate here that testosterone is produced by the ovary of Wnt-4-deficient female embryos and is also detected in the embryonic plasma.

Comparison of effect of BMP-2, -4, and -6 on in vitro cartilage formation of human adult stem cells from bone marrow stroma.

The human adult stem cells from bone marrow stroma referred to as mesenchymal stem cells or marrow stromal cells (MSCs) are of interest because they are easily isolated and expanded and are capable of multipotential differentiation. Here, we examined the ability of recombinant human bone morphogenetic protein (BMP)-2, -4, and -6 to enhance in vitro cartilage formation of MSCs. Human MSCs were isolated from bone marrow taken from normal adult donors.

Developmental diethylstilbestrol exposure alters genetic pathways of uterine cytodifferentiation.

The formation of a simple columnar epithelium in the uterus is essential for implantation. Perturbation of this developmental process by exogenous estrogen, such as diethylstilbestrol (DES), results in uterine metaplasia that contributes to infertility. The cellular and molecular mechanism underlying this transformation event is not well understood.

Adipogenic differentiation of human adult stem cells from bone marrow stroma (MSCs).

Unlabelled: We assayed gene expressions during adipogenesis of human MSCs. Microarray assays demonstrated time-dependent increases in expression of 67 genes, including 2 genes for transcription factors that were not previously shown to be expressed during adipogenesis. INTRODUCTION Increased numbers of bone marrow adipocytes have been observed in patients with osteoporosis and aplastic anemia, but the pathological mechanisms remain unknown.

In vitro cartilage formation by human adult stem cells from bone marrow stroma defines the sequence of cellular and molecular events during chondrogenesis.

One approach to resolving the complexities of chondrogenesis is to examine simplified systems in vitro. We analyzed cartilage differentiation by human adult stem cells from bone marrow stroma. Marrow stromal cells were cultured as micromass pellets for 21 days in serum-free medium containing transforming growth factor (TGF)-beta3, dexamethasone, and bone morphogenetic protein (BMP)-6.