Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “microenvironment”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,243 records · Page 69Linked to original sources
PubMed1993

In situ hybridisation for cytokine gene transcripts in the solid tumour microenvironment.

To determine if mononuclear cells (MNC) infiltrating various types of human solid tumours express genes for cytokines, in situ hybridisation with 35S-labelled cDNA antisense probes for interleukin 2 (IL2), interferon gamma (IFN-gamma), tumour necrosis factor alpha (TNF-alpha), interleukin 1-beta (IL1-beta), transforming growth factor beta (TGF-beta) and interleukin 2-receptors (IL2R) was performed. Fresh-frozen tissue samples of ovarian carcinomas (n = 13), breast carcinomas (n = 12), and squamous cell carcinomas of the head and neck (SCCHN, n = 7) were evaluated for the presence and localization in the tumour of MNC positive for cytokine genes. In ovarian tumours and those breast carcinomas producing little or no mucin, only rare positive MNC were observed. In contrast, breast carcinomas producing mucin and all SCCHN contained numerous MNC expressing gene transcripts for IL2, IFN-gamma, TNF-alpha, IL2R as well as TGF-beta. In tumour-involved lymph nodes of patients with SCCHN, MNC expressing genes for cytokines were found around tumour metastases but not in non-involved areas. These data suggest that tumours expressing immunogenic antigens (e.g. mucin) contain many activated MNC, while other tumours either fail to activate or suppress functions of infiltrating MNC. In SCCHN or tumour-draining lymph nodes, local down-regulation of antitumour responses might be mediated by TGF-beta produced by activated tumour-infiltrating MNC.

Breast Neoplasms↗
PubMed1994

A technique for successful transplantation of tumours into ear-pouches of nude mice to maintain and study the tumour microenvironment.

We have applied a technique which was originally used for cardiac transplantation in mice, to the transplantation of human breast cancers. To our knowledge previous reports of this method for tumour xenografting have not been made. This technique has wider application for many non-vascularised tissue allografts, including for example synovial grafts for arthritis research or other tumour types in oncology research. The method is simple and reproducible within the limits of the experiments reported.

Animals↗
PubMed1996

Adhesion of multiple myeloma cells to the bone marrow microenvironment: implications for future therapeutic strategies.

Multiple myeloma is characterized by excess plasma cells within the bone marrow in association with monoclonal antibody protein in the serum and/or urine. Tumor cells localize within the marrow via an interaction of cell-surface adhesion molecules with their respective ligands on marrow stromal cells and extracellular matrix proteins. Stimulation of myeloma cells via these cell-surface molecules, either directly or via tumor cell adhesion to stromal cells, can induce autocrine or paracrine tumor cell growth mediated by interleukin 6. It might therefore be possible to develop innovative treatment strategies either to inhibit interleukin 6 production or to interrupt interleukin 6 signal transduction in multiple myeloma.

Antibodies, Monoclonal↗
PubMed2004

Gene expression profiling in the inductive human hematopoietic microenvironment.

Human hematopoietic stem cells (HSCs) and their progenitors can be maintained in vitro in long-term bone marrow cultures (LTBMCs) in which constituent HSCs can persist within the adherent layers for up to 2 months. Media replenishment of LTBMCs has been shown to induce transition of HSCs from a quiescent state to an active cycling state. We hypothesize that the media replenishment of the LTBMCs leads to the activation of important regulatory genes uniquely involved in HSC proliferation and differentiation. To profile the gene expression changes associated with HSC activation, we performed suppression subtractive hybridization (SSH) on day 14 human LTBMCs following 1-h media replenishment and on unmanipulated controls. The generated SSH library contained 191 differentially up-regulated expressed sequence tags (ESTs), the majority corresponding to known genes related to various intracellular processes, including signal transduction pathways, protein synthesis, and cell cycle regulation. Nineteen ESTs represented previously undescribed sequences encoding proteins of unknown function. Differential up-regulation of representative genes, including IL-8, IL-1, putative cytokine 21/HC21, MAD3, and a novel EST was confirmed by semi-quantitative RT-PCR. Levels of fibronectin, G-CSF, and stem cell factor also increased in the conditioned media of LTBMCs as assessed by ELISA, indicating increased synthesis and secretion of these factors. Analysis of our library provides insights into some of the immediate early gene changes underlying the mechanisms by which the stromal elements within the LTBMCs contribute to the induction of HSC activation and provides the opportunity to identify as yet unrecognized factors regulating HSC activation in the LTBMC milieu.

Bone Marrow Cells↗
PubMed2007

Cholesterol: Coupling between membrane microenvironment and ABC transporter activity.

Lipid composition of biological membranes is closely related to the function of the ATP-binding cassette (ABC) transporter P-Glycoprotein (Pgp). Herein, we studied how membrane physico-chemical properties affect Pgp-activity. We effectively modulated the cellular cholesterol content using methyl-beta-cyclodextrin (MbetaCD) and MbetaCD-cholesterol-inclusion complex. Pgp was not liberated from the plasma membrane during cholesterol modulation and functional inhibition of Pgp was related to varying cholesterol levels in the plasma membrane. Our data indicate that membrane fluidity does not solely account for cholesterol dependent modifications of Pgp-activity. Therefore, we isolated lipid rafts and examined distinct membrane microdomains. Both depletion and cholesterol enrichment induces a disassembly of lipid rafts. In cholesterol-depleted cell membranes a shift in the Pgp localisation to detergent soluble fractions was observed. Enrichment of membrane cholesterol changed lipid raft distribution but not the localisation of Pgp. From our data we conclude that Pgp-transport capacity depends on accurate lipid raft properties.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMedDate not supplied

Myeloma cells (5TMM) and their interactions with the marrow microenvironment.

Myeloma is a deadly B-cell neoplasm, characterized by the monoclonal proliferation of plasma cells, the development of osteolytic lesions, and the induction of angiogenesis. Myeloma cells are predominantly localized in the marrow where they receive the appropriate survival and proliferation signals. To reach or spread over the marrow, the myeloma cells need to migrate from the vascular to the extravascular compartment of the marrow. A process called "homing". In this review, the steps of the homing scheme, analyzed in the 5TMM model, will be described. These murine models originated from spontaneously developed myeloma in elderly mice and have since been propagated by intravenous injection of myeloma cells into young syngeneic mice. These models resemble the human condition closely. The different studies reported here demonstrate that adhesion of 5TMM cells to marrow endothelial cells is partially mediated by CD44v10 and to stromal cells by CD44v6. The 5TMM cells migrate to the marrow through the effects of MCP-1, laminin-1, and IGF-1. Once past the marrow endothelium, they invade the extravascular compartment of the marrow by secreting MMP-9 and uPA. When they have settled in the marrow, they become susceptible to the effects of IGF-1, which stimulates the cells to proliferate and produce VEGF. Furthermore, studies targeting the marrow with inhibitors will be highlighted. These studies show that the 5TMM models are useful for unraveling basic biological processes and for identifying new therapeutic targets.

Animals↗
PubMedDate not supplied

Human bone marrow CD34+ progenitor cells mature to T cells on OP9-DL1 stromal cell line without thymus microenvironment.

In this paper, we confirm data reported by the group of Zúñiga-Pflücker that human cord blood CD34(+)38(-)Lin- progenitor cells when co-cultured with the murine stromal cell line OP9-DL engineered to express the Notch ligand delta-like-1 mature into T lymphocytes with a phenotypic progression as the one seen in thymus. We show that this is also the case for human T cells starting from CD34(+) adolescent bone marrow cells. These findings offer the theoretical possibility to generate ex vivo human T cells and administer them in vivo in patients to overcome their immune deficient window period after transplantation. However, the practical and theoretical problems that this new technology has to overcome before this technique can be applied in clinic are still enormous and discussed.

Adolescent↗
PubMed2005

3D microenvironment as essential element for osteoinduction by biomaterials.

In order to unravel the mechanism of osteoinduction by biomaterials, in this study we investigated the influence of the specific surface area on osteoinductive properties of two types of calcium phosphate ceramics. Different surface areas of the ceramics were obtained by varying their sintering temperatures. Hydroxyapatite (HA) ceramic was sintered at 1150 and 1250 degrees C. Biphasic calcium phosphate (BCP) ceramic, consisting of HA and beta-tricalcium phosphate (beta-TCP), was sintered at 1100, 1150 and 1200 degrees C. Changes in sintering temperature did not influence the chemistry of the ceramics; HA remained pure after sintering at different temperatures and the weight ratio of HA and beta-TCP in the BCP was independent of the temperature as well. Similarly, macroporosity of the ceramics was unaffected by the changes of the sintering temperature. However, microporosity (pore diameter <10 microm) significantly decreased with increasing sintering temperature. In addition to the decrease of the microporosity, the crystal size increased with increasing sintering temperature. These two effects resulted in a significant decrease of the specific surface area of the ceramics with increasing sintering temperatures. Samples of HA1150, HA1250, BCP1100, BCP1150 and BCP1200 were implanted in the back muscles of Dutch milk goats and harvested at 6 and 12 weeks post implantation. After explantation, histomorphometrical analysis was performed on all implants. All implanted materials except HA1250 induced bone. However, large variations in the amounts of induced bone were observed between different materials and between individual animals. Histomorphometrical results showed that the presence of micropores within macropore walls is necessary to make a material osteoinductive. We postulate that introduction of microporosity within macropores, and consequent increase of the specific surface area, affects the interface dynamics of the ceramic in such a way that relevant cells are triggered to differentiate into the osteogenic lineage.

Animals↗
PubMed2006

Evaluation of silicon nanoporous membranes and ECM-based microenvironments on neurosecretory cells.

Understanding the interactions between microfabricated synthetic interfaces and cultured cells expressing a neuronal phenotype are critical for advancing research in the field of neural engineering such as neural recording and stimulation and neural microdevice interactions with the human brain. Here we explore the integration of these two components for therapeutic applications of neural prostheses. Microfabricated silicon nanoporous membranes were investigated for their effects on survival, proliferation, and differentiation of the well-known PC12 clonal line. Specifically, cell morphology, examined through fluorescence staining, were comparable in many respects on both silicon membrane and widely-used polystyrene culture surfaces. The attachment and differentiation of PC12 cells cultured on collagen and laminin-modified membranes and standard tissue culture surfaces were similar. Lastly, the differentiation response and tyrosine hydroxylase activity of PC12 cells embedded in a type I collagen matrix on experimental membrane substrates while exposed to NGF were significant and indistinguishable from tissue-culture polystyrene (TC-PS) surfaces. Results from this research suggest that microfabricated silicon nanoporous membranes may be useful, biocompatible permselective structures for neuroprosthetic applications and that collagen may be a useful immobilizing matrix for PC12 cells loaded in implantable macroencapsulation devices designed for the treatment of neurodegenerative disorders.

Animals↗
PubMed2004

Preparation of alkylation agents for bulged DNA microenvironments.

A designed molecule with capacity to alkylate DNA bulges has been prepared from readily available starting materials. The spirocyclic template utilized was designed on the basis of established architectures, and equipped with a mustard alkylating group. Preliminary studies confirm alkylation of specific bulged sequences, paving the way for second generation substrates with higher affinity.

Alkylating Agents↗
PubMed2006

Properties of microsolvated ions: from the microenvironment of chromophore and alkali metal ions in proteins to negative ions in water clusters.

Here we discuss the fascinating chemistry and physics of microsolvated ions that bridge the transition from bare ions in gas phase to ions in solution. Such ions occur in many situations in biochemistry and are crucial for several functions; metal ions, for example, must remove their water shell to pass through ion pumps in membranes. Furthermore, only a few water molecules are buried in the hydrophobic pockets of proteins where they are bound to charged amino acid residues or ionic chromophores. Another aspect is the reactivity of microsolvated ions and the importance in atmospheric, organic and inorganic chemistry. We close by a discussion of the stability of molecular dianions, and how hydration affects the electronic binding energy. There is a vast literature on microsolvated ions, and in this review we are far from being comprehensive, rather we mainly bring examples of our own work.

Anions↗
PubMed2005

Susceptibility to colon carcinogenesis in C3H<-->C57BL/6 chimeric mice reflects both tissue microenvironment and genotype.

Considerable rodent strain differences have been documented with regard to susceptibility to colon carcinogens. To clarify mechanisms, chimeras of susceptible strain C3H and relatively resistant strain C57BL/6N (B6) mice were exposed to a colonotropic carcinogen, 1,2-dimethylhydrazine (DMH) and tumor incidence and multiplicity were assessed. In the chimeras, incidence was as high as the C3H level. Multiplicity of lesions of B6 cells was also increased (P<0.001), but maintenance of the strain difference. When tumor localization was analyzed, tumors of B6 genotype in chimeras demonstrated a greater spread of distribution than in the parental case. The chimeric environment may thus stimulate tumor initiation but cell autonomous suppressive factors may be retained.

Animals↗