Expression Of Ties Research Articles

De nouvelles normes à l’égard des restes humains anciens : de la réification à la personnalisation?

Les normes à l’égard des restes humains, anciens ou plus récents, sont en passe de se transformer ; on assiste à des ajustements inédits tendant à humaniser ces restes. Certains d’entre eux, dans des contextes fort différents, sont désormais traités comme des dépouilles mortelles et peuvent bénéficier d’un traitement qui pourrait être qualifié de funéraire et aboutir au cimetière. Ces changements sont fréquemment interprétés comme la résultante de l’expression de liens (liens familiaux, affiliation communautaire) favorisant un processus de deuil ou une dynamique mémorielle. Or une seconde tendance consiste à appliquer des principes dédiés à la dépouille mortelle à des restes humains jusqu’alors réifiés, notamment le principe de la dignité humaine. Elle s’observe à deux niveaux, celui de la doctrine juridique et celui des pratiques. Cet article s’appuie sur une illustration tirée d’une fouille archéologique préventive récente, laquelle permet de saisir à la fois les enjeux, mais aussi les réponses adoptées in situ au sujet de la trajectoire et du devenir de ces restes humains.

Expression of Tie-1 and 2 receptors, and angiopoietin-1, 2 and 4 in gastric carcinoma; immunohistochemical analyses and correlation with clinicopathological factors.

There is strong evidence that tyrosine kinases are involved in the regulation of tumour progression, cellular growth and differentiation. Recently, many kinds of tyrosine kinase receptors have been reported, and among them Tie-1 and 2 constitute a major class. Angiopoietin (Ang)-1 is known as a ligand of the Tie-2 tyrosine kinase receptor. The aim of this study was to determine the expression profile of Tie-1 and 2 and Ang-1, 2 and 4 in gastric adenocarcinoma. Eighty-nine cases of surgically resected human gastric adenocarcinoma were studied by immunohistochemistry. Of these, 60 (67.4%), 61 (68.5%), 69 (77.5%), 75 (84.3%), and 47 cases (52.8%) showed positive staining in the cytoplasm of carcinoma cells for the Tie-1 and 2 and Ang-1, 2 and 4 proteins, respectively. The expression of Ties and Angs was significantly correlated with several type of histological differentiation and several clinicopathological factors. Ties and Angs were highly expressed in human gastric adenocarcinoma cells. These findings suggest that the Tie-Ang receptor-ligand complex is one of the factors involved in the cellular differentiation and progression of human gastric adenocarcinoma.

Expression and Function of Murine Receptor Tyrosine Kinases, TIE and TEK, in Hematopoietic Stem Cells

AbstractTwo highly related receptor tyrosine kinases, TIE and TEK, comprise a family of endothelial cell-specific kinase. We established monoclonal antibodies against them and performed detailed analyses on their expression and function in murine hematopoietic stem cells (HSCs). TIE and TEK were expressed on 23.7% and 33.3% of lineage marker-negative, c-Kit+ and Sca-1+ (Lin− c-Kit+ Sca-1+) HSCs that contain the majority of day-12 colony-forming units-spleen (CFU-S) and long-term reconstituting cells, but not committed progenitor cells. Lin− c-Kit+ Sca-1+ cells were further divided by the expression of TIE and TEK. TIE+ and TEK+ HSCs as well as each negative counterpart contained high proliferative potential colony-forming cells and differentiated into lymphoid and myeloid progenies both in vitro and in vivo. However, day-12 CFU-S were enriched in TIE+ and TEK+ HSCs. Our findings define TIE and TEK as novel stem cell marker antigens that segregate day-12 CFU-S, and provide evidence of novel signaling pathways that are involved in the functional regulation of HSCs at a specific stage of differentiation, particularly of day-12 CFU-S.

The Tie Receptor Tyrosine Kinase Is Expressed by Human Hematopoietic Progenitor Cells and by a Subset of Megakaryocytic Cells

Growth factor receptors in human hematopoietic progenitor cells have become the focus of intense interest, because they may provide tools for the monitoring, enrichment, and expansion of stem cells. We have shown earlier that the Tie receptor tyrosine kinase is expressed in erythroid and megakaryoblastic human leukemia cell lines, in the blood islands of the yolk sac, and in endothelial cells starting from day 8.0 of mouse development. Here, the expression of Tie was studied in human hematopoietic cells of various sources. Peripheral blood mononuclear cells were Tie-. However, a large fraction of CD34+ cells from umbilical cord blood (UCB) and bone marrow (BM) expressed tie protein and mRNA. On average, 64% of the fluorescence-activated cell sorting-gated UCB CD34+ cells including CD38- cells and a fraction of cells expressing low levels of c-Kit were Tie+. Also, 30% to 60% of BM CD34+ cells were Tie+, including most of the BM CD34+CD38-, CD34+Thy-1+, and CD34+HLA-DR- cells. Under culture conditions allowing myeloid, erythroid, and/or megakaryocytic differentiation, purified UCB CD34+ cells lost Tie mRNA and protein expression concomitantly with that of CD34; however, a significant fraction of cells expressed Tie during megakaryocytic differentiation. These data suggest that, in humans, the Tie receptor and presumably its ligand may function at an early stage of hematopoietic cell differentiation.

In vivo modulators of antibody kinetics.

The aim of the present study was to summarize the effect of in vivo modulation of antibody kinetics and to present new data on the in vivo effect of the cell membrane active detergent Tween 80 and the cytokine interleukin-2 (IL-2) on the accumulation and clearance of a radioactive antibody. Mice bearing Lewis lung carcinoma xenografts and rats bearing DMBA-induced mammary carcinomas were studied after injecting I-125 labeled IgG1 monoclonal antibody (3c4c7g6) raised against a tyrosine kinase receptor protein Tie. Expression of Tie is known to be abundant in vascular endothelia and possibly related to malignant angiogenesis. Tween 80 was administered intratumorally (0.04% of tumor volume), whereas IL-2 was administered intraperitoneally. In the Lewis lung tumor model, the absolute tumor uptake varied between 2 and 5% ID/g, and maximum uptake was achieved after 24 h with Tween, and after 48 h without Tween. Tween manipulation did not increase the uptake in any normal organ, but it enhanced antibody clearance from the blood. In the DMBA rat model, IL-2 had no effect on blood clearance, but enhanced the uptake of Tie antibody into the tumor from 2.5-0.9 to 4.5-0.4% ID/g at 48 h. These data indicate that antibody biodistribution and pharmacokinetics can be modulated by a surface detergent and a cytokine, giving decreased exposure to critical organs, and increased uptake into the tumor. This type of manipulation provides an opportunity to optimize radioimmunotherapy.

Predominant expression of a receptor tyrosine kinase, TIE, in hematopoietic stem cells and B cells

A receptor tyrosine kinase (RTK), TIE (tyrosine kinase that contains immunoglobulin-like loops and epidermal growth factor [EGF] homology domains), is expressed in vascular endothelial and hematopoietic cells. We generated monoclonal antibodies (MoAbs) against the extracellular domain of TIE and a polyclonal antibody against the TIE carboxyterminus and used them to analyze expression of TIE in hematopoietic cells. Western blotting detected two forms of TIE protein with a molecular mass of 135 and 130 kD in hematopoietic and endothelial cells. Northern blotting analysis revealed that TIE was expressed preferentially in undifferentiated cell lines, especially when megakaryocytic, but not erythroid differentiation was induced. Reverse transcriptase-polymerase chain reaction (RT-PCR) showed that TIE was predominantly expressed in the human hematopoietic progenitor fraction, CD34+ cells. Fluorescence-activated cell sorting (FACS) showed that 42% of CD34+ and 17% of KIT-positive (KIT+) cells were TIE-positive (TIE+). The majority (81%) of the primitive hematopoietic stem cells, CD34+CD38- cells, were TIE+. Assays of progenitor cells and long-term culture-initiating cells (LTC-IC) showed that the TIE+ fraction contained more primitive cells than the TIE- fraction. Some TIE+ cells were in the CD34- fraction, which were CD19+ and CD20+ (B cells). These findings indicate that TIE has a unique spectrum of expression in primitive hematopoietic stem cells and B cells. Although its ligand has not been identified, TIE and its ligand may establish a novel regulatory pathway not only in early hematopoiesis, but also in the differentiation and/or proliferation of B cells.