Tirofiban induces VEGF production and stimulates migration and proliferation of endothelial cells.

Tirofiban is a fibrinogen receptor antagonist, generated using the tripeptide Arg-Gly-Asp (RGD) as a template. RGD activates integrin receptors and integrin-mediated signals are necessary for normal cells to promote survival and stimulate cell cycle progression. We investigated whether tirofiban activated growth-stimulatory signals in endothelium.

FKBP51 increases the tumour-promoter potential of TGF-beta.

Background: FKBP51 (FKBP5 Official Symbol) is a large molecular weight component of the family of FK506 binding proteins (FKBP). In recent years, research studies from our laboratory highlighted functions for FKBP51 in the control of apoptosis and melanoma progression. FKBP51 expression correlated with the invasiveness and aggressiveness of melanoma.

Synergy between enzastaurin doxorubicin in inducing melanoma apoptosis.

Melanoma is resistant to most standard chemotherapeutics. We analysed the combined effect of doxorubicin and enzastaurin on cell death of four melanoma cell lines, namely G361, SK-MEL3, A375 and SAN. Enzastaurin IC50 was calculated by measure of growth inhibition with MTS assay and corresponded to 2 μM; the half maximal cytotoxicity of doxorubicin was obtained at 3 μM dose.

FK506 binding protein 51 positively regulates melanoma stemness and metastatic potential.

Melanoma is the most aggressive skin cancer; there is no cure in advanced stages. Identifying molecular participants in melanoma progression may provide useful diagnostic and therapeutic tools. FK506 binding protein 51 (FKBP51), an immunophilin with a relevant role in developmental stages, is highly expressed in melanoma and correlates with aggressiveness and therapy resistance.

Toxoplasma gondii Dense Granule Antigen 1 stimulates apoptosis of monocytes through autocrine TGF-β signaling.

Monocyte/macrophages represent the first line of defense against protozoan parasites. Different mechanisms of monocyte suppression by Toxoplasma gondii that sustain parasite invasion and persistence have been described, including apoptosis. In the present study, we investigated the effect of microbial excretory–secretory polypeptides, namely the microneme protein MIC3 and the dense granule antigen GRA1, on apoptosis of monocytes from patients with congenital toxoplasmosis and healthy individuals.

FK506 binding proteins as targets in anticancer therapy.

FK506 binding proteins (FKBPs) are the intracellular ligands of FK506 and rapamycin, two natural compounds with powerful and clinically efficient immunosuppressive activity. In recent decades, a relevant role for immunosuppressants as anticancer agents has emerged. Especially, rapamycin and its derivatives are used, with successful results, across a variety of tumors.

Role of FK506-binding protein 51 in the control of apoptosis of irradiated melanoma cells.

FK506-binding protein 51 (FKBP51) is an immunophilin with isomerase activity, which performs important biological functions in the cell. It has recently been involved in the apoptosis resistance of malignant melanoma. The aim of this study was to investigate the possible role of FKBP51 in the control of response to ionizing radiation (Rx) in malignant melanoma.

The effect of FK506 on transforming growth factor beta signaling and apoptosis in chronic lymphocytic leukemia B cells.

Background: Loss of response to transforming growth factor-beta (TGF-beta ) is thought to contribute to the progression of chronic lymphocytic leukemia. Recent findings of over-activation of the TGF-beta signal in FKBP12-knockout mouse prompted us to investigate whether FK506, the canonical ligand of FKBP, can activate the TGF-beta signal in chronic lymphocytic leukemia.

Design And Methods: We studied 62 chronic lymphocytic leukemia samples from patients with Rai/Binet stage 0 to 4 disease.

Increased CD154 expression in uninfected infants born to HIV-positive mothers exposed to antiretroviral prophylaxis.

Although prevention of mother-to-child HIV transmission by antiretroviral drugs has been shown to be effective, the short- and long-term effects of treatment are not well known. Several reports suggest that antiretroviral drugs act not only by inhibiting viral replication, but also by improving antiviral immunity. In particular, treatment with nucleoside analogs was found to increase CD40 ligand (CD40L; CD154) levels, an inducible molecule expressed on activated T lymphocytes.

Rapamycin stimulates apoptosis of childhood acute lymphoblastic leukemia cells.

The phosphatidyl-inositol 3 kinase (PI3k)/Akt pathway has been implicated in childhood acute lymphoblastic leukemia (ALL). Because rapamycin suppresses the oncogenic processes sustained by PI3k/Akt, we investigated whether rapamycin affects blast survival. We found that rapamycin induces apoptosis of blasts in 56% of the bone marrow samples analyzed.

Evaluation of the monocyte counting by two automated haematology analysers compared with flow cytometry.

The aim is to determine the monocyte count performance of the Bayer Diagnostics ADVIA120 and Coulter LH 750 automated haematology analysers and the results obtained by these two instruments were compared with those provided by Becton Dickinson FACScan flow cytometer using the combination of CD45/CD14 MoAb. Linearity and imprecision were also evaluated. The linearity of both instruments was good.

Rapamycin inhibits doxorubicin-induced NF-kappaB/Rel nuclear activity and enhances the apoptosis of melanoma cells.

Inhibition of nuclear factor (NF)-kappaB/Rel can sensitise many tumour cells to death-inducing stimuli, including chemotherapeutic agents, and there are data suggesting that disruption of NF-kappaB may be of therapeutic interest in melanoma. We found that rapamycin sensitised a human melanoma cell line, established from a patient, to the cytolytic effects of doxorubicin. Doxorubicin is a striking NF-kappaB/Rel-inducer, we therefore investigated if rapamycin interfered with the pathway of NF-kappaB/Rel activation, i.

Activation of NF-kappaB/Rel transcription factors in human primary peripheral blood mononuclear cells by interleukin 7.

Pathways that regulate the activation of NF-kappaB/Rel transcription factors are known to include signaling through a number of cytokine receptors. Interleukin 7 (IL-7), produced by bone marrow and other stromal cells, is a key factor for differentiation and survival in the lymphoid and other compartments. We found that human recombinant IL-7 induced NF-kappaB/Rel activation, analyzed by electrophoretic mobility shift assay (EMSA), in human peripheral blood T lymphocytes from healthy donors.

NF-kappaB/Rel-mediated regulation of apoptosis in hematologic malignancies and normal hematopoietic progenitors.

The activity of NF-kappaB/Rel transcription factors can downmodulate apoptosis in normal and neoplastic cells of the hematologic and other compartments, contributing in maintaining neoplastic clone survival and impairing response to therapy. Alterations in nfkappab or ikappaB genes are documented in some hematologic neoplasias, while in others dysfunction in NF-kappaB/Rel-activating signaling pathways can be recognized. The prosurvival properties of NF-kappaB/Rel appear to rely on the induced expression of molecules (caspase inhibitors, Bcl2 protein family members, etc.

Increased expression of CD40 ligand in activated CD4+ T lymphocytes of systemic sclerosis patients.

CD40-CD154 interactions play a key role in regulating immune response and are involved in the development of some autoimmune diseases. We analysed the expression of CD154 antigen in CD3-activated PBMC from 10 systemic sclerosis (SSc) patients and 10 control subjects by immunofluorescence. PBMC from SSc patients showed an increased expression of this molecule, since, 6 h following CD3 stimulation, the percentage of CD154(+)cells was of 17.

Enhancement of cytosine arabinoside-induced apoptosis in human myeloblastic leukemia cells by NF-kappa B/Rel- specific decoy oligodeoxynucleotides.

The activity of NF-kappa B/Rel nuclear factors is known to inhibit apoptosis in various cell types. We investigated whether the subtraction of NF-kappa B/Rel activity influenced the response of 11 AML (M1, M2 and M4) patients' cells to AraC. To this end we used a phosphorothioate double-stranded decoy oligodeoxynucleotide (ODN) carrying the NF-kappa B/Rel- consensus sequence.

Amifostine inhibits hematopoietic progenitor cell apoptosis by activating NF-kappaB/Rel transcription factors.

We investigated the involvement of NF-kappaB/Rel transcription factors that reportedly can inhibit apoptosis in various cell types in the antiapoptotic mechanism of the cytoprotectant amifostine. In the nontumorigenic murine myeloid progenitor 32D cells incubated with amifostine, we detected a reduction of the IkappaBalpha cytoplasmic levels by Western blotting and a raising of nuclear NF-kappaB/Rel complexes by electrophoretic mobility shift assay. Amifostine inhibited by more than 30% the growth factor deprivation-induced apoptosis, whereas its effect failed when we blocked the NF-kappaB/Rel activity with an NF-kappaB/Rel-binding phosphorothioate decoy oligodeoxynucleotide.

Induction of nuclear factor kappa B/Rel nuclear activity in human peripheral blood T lymphocytes by anti-HLA class I monoclonal antibodies.

Monoclonal antibodies against either monomorphic or polymorphic determinants of class I antigen induced in PBMC and highly purified T lymphocytes the nuclear activity of NF-kappa B/Rel complexes. These included both p50/p50 and p50/p65 dimers, recognized by specific antibodies in EMSA. The induced complexes were detectable in extracts of cells incubated with anti-class I monoclonal antibody (mAb) for 1.

IL-10 inhibits nuclear factor-kappa B/Rel nuclear activity in CD3-stimulated human peripheral T lymphocytes.

IL-10 markedly reduces nuclear factor (NF)-kappa B/Rel nuclear activity induced in PBMC by stimulation with the anti-CD3 mAb OKT3. The inhibition is exerted specifically on the NF-kappa B/Rel activation induced by mAb OKT3, and not that produced by PMA. As judged by supershifting the DNA-protein complexes with Abs recognizing specific components of the NF-kappa B/Rel protein family, the p50/p65 (Rel A) heterodimeric form of NF-kappa B is primarily affected.

Regulation of NF-kappa B nuclear activity in peripheral blood mononuclear cells: role of CD28 antigen.

The NF-kappa B/rel family of transcription factors regulates the expression of a number of genes, including interleukin 2 (IL-2), IL-2 receptor alpha chain (Tac), and others, controlling T lymphocyte activation. The CD28 antigen is involved in regulation of T cell activation. To investigate whether CD28 antigen regulates NF-kappa B factors, we analyzed the effect of an anti-CD28 monoclonal antibody (mAb), CLB-CD28/1, on the nuclear activity of NF-kappa B complexes in resting and CD3-activated peripheral blood mononuclear cells (PBMC) of 11 donors.