Correlation between nuclear factor-kappaB activity in bronchial brushing samples and lung dysfunction in an animal model of asthma.

Asthma is a chronic inflammatory disease of the airways, in which many inflammatory genes are overexpressed. Transcription factor, nuclear factor-kappaB (NF-kappaB), which is thought to control the transcriptional initiation of inflammatory genes, has been poorly investigated in asthma. In the present report, bronchial cells (BCs), recovered by bronchial brushing in healthy and heaves-affected horses (i.

TNP-470, a potent angiogenesis inhibitor, amplifies human T lymphocyte activation through an induction of nuclear factor-kappaB, nuclear factor-AT, and activation protein-1 transcription factors.

TNP-470, an angiogenesis inhibitor derived from fumagillin, is foreseen as a promising anti-cancer drug. Its effectiveness to restrain tumor growth and its lack of major side effects have been demonstrated in several animal models and have led the drug to reach phase III clinical trials. Beside its antiangiogenesis activities, TNP-470 exhibits several effects on the immune system.

Cell type-specific role for reactive oxygen species in nuclear factor-kappaB activation by interleukin-1.

The role of reactive oxygen intermediates (ROIs) in nuclear factor-kappaB (NF-kappaB) activation remains a matter of controversy. We have studied whether ROIs played any role in NF-kappaB induction by interleukin-1beta (IL-1beta) in different cell types. Our studies indicated three different pathways.

The homeodomain-containing proteins: an update on their interacting partners.

Homeodomain-containing proteins are transcription regulators controlling the coordinated expression of genes involved in development, differentiation, and cellular transformation. They share a highly conserved 60-amino-acid region (the "homeodomain"), which allows them to bind DNA and modulate the expression of multiple target genes, whose identities remain largely unknown. Although each HOX gene product exhibits in vivo specificity, they harbor very similar DNA-binding affinities in vitro, suggesting that other mechanisms such as protein-protein interactions are critical to modulate their function.

A cell type-specific and gap junction-independent mechanism for the herpes simplex virus-1 thymidine kinase gene/ganciclovir-mediated bystander effect.

Tumor cells expressing the herpes simplex virus type 1 thymidine kinase (HSV-tk) gene are killed by nucleoside analogues such as ganciclovir (GCV). GCV affects not only the cells expressing HSV-tk but also neighboring cells that do not express the gene; this phenomenon commonly is called "bystander effect." GCV metabolites transfer via gap junctional intercellular communication (GJIC) accounts for the bystander effect in different cell lines, but other mechanisms have also been described.

CBP and histone deacetylase inhibition enhance the transactivation potential of the HOXB7 homeodomain-containing protein.

Homeodomain-containing proteins are transcription factors regulating the coordinated expression of multiple target genes involved in development, differentiation and cellular transformation. In this study, we demonstrated that HOXB7, one member of this family, behaved as a transactivator in breast cancer cells. Deletion of either the HOXB7 N-terminal domain or the C-terminal acidic tail abolished this transcriptional effect, suggesting a combination of distinct functional transactivating domains.

Regulation of NF-kappaB activity by I kappaB-related proteins in adenocarcinoma cells.

Constitutive NF-kappaB activity varies widely among cancer cell lines. In this report, we studied the expression and the role of different I kappaB inhibitors in adenocarcinoma cell lines. High constitutive NF-kappaB activity and low I kappaB-alpha expression was found in a number of these cell lines.

Repeated cycles of retrovirus-mediated HSVtk gene transfer plus ganciclovir increase survival of rats with peritoneal carcinomatosis.

Peritoneal carcinomatosis is a common clinical situation that requires novel therapeutic approaches. We investigated the efficiency of an HSVtk gene therapy for the treatment of peritoneal carcinomatosis induced in syngeneic rats by DHD/K12 colon carcinoma cells. In this setting, the efficiency of two different retrovirus producing cell lines (GP+AmEnv12 and FLYA13) was compared.

Peripheral blood progenitor cell collections in cancer patients: analysis of factors affecting the yields.

Background And Objective: Peripheral blood progenitor cells (PBPC) are now widely used to restore hematopoiesis following high dose chemotherapy in patients with malignancies. We sought to identify parameters that could predict the yield of PBPC after mobilization with chemotherapy (CT) with or without granulocyte colony-stimulating factor (G-CSF) in cancer patients.

Design And Methods: One hundred and fifty patients underwent 627 PBPC collections during the recovery phase following CT with (n = 469) or without (n = 142) G-CSF.

[Malignant tumors of unknown origin].

Cancers of unknown origin form a specific clinical entity. The diagnostic procedure has to be guided by the therapeutical possibilities and requires a biopsy. Immunohistology, electron microscopy and cytogenetics are informative for carcinomas and poorly differentiated adenocarcinomas.

Role of the protein kinase C lambda/iota isoform in nuclear factor-kappaB activation by interleukin-1beta or tumor necrosis factor-alpha: cell type specificities.

It has previously been reported that distinct signaling pathways can lead to nuclear factor (NF)-kappaB activation following stimulation of different cell types with inflammatory cytokines. As the role of atypical protein kinase C (PKC) isoforms in NF-kappaB activation remains a matter of controversy, we investigated whether this role might be cell type-dependent. Immunoblots detected atypical PKC expression in all the analyzed cell lines.

Stable inhibition of nuclear factor kappaB in cancer cells does not increase sensitivity to cytotoxic drugs.

Several reports indicated that nuclear factor kappaB (NF-kappaB) activation by cytokines, cytotoxic drugs, or ionizing radiation protects cells against apoptosis. Therefore, we investigated the consequence of NF-kappaB inhibition on the efficiency of antineoplastic agents. HPB, HCT116, MCF7, and OVCAR-3 cells stably expressing a dominant negative IkappaBalpha inhibitor showed a decreased NF-kappaB activation following treatment with tumor necrosis factor a and various chemotherapeutic agents.

IkappaB-alpha enhances transactivation by the HOXB7 homeodomain-containing protein.

Combinatorial interactions between distinct transcription factors generate specificity in the controlled expression of target genes. In this report, we demonstrated that the HOXB7 homeodomain-containing protein, which plays a key role in development and differentiation, physically interacted in vitro with IkappaB-alpha, an inhibitor of NF-kappaB activity. This interaction was mediated by the IkappaB-alpha ankyrin repeats and C-terminal domain as well as by the HOXB7 N-terminal domain.

Reactive oxygen intermediate-dependent NF-kappaB activation by interleukin-1beta requires 5-lipoxygenase or NADPH oxidase activity.

We previously reported that the role of reactive oxygen intermediates (ROIs) in NF-kappaB activation by proinflammatory cytokines was cell specific. However, the sources for ROIs in various cell types are yet to be determined and might include 5-lipoxygenase (5-LOX) and NADPH oxidase. 5-LOX and 5-LOX activating protein (FLAP) are coexpressed in lymphoid cells but not in monocytic or epithelial cells.

Pyropheophorbide-a methyl ester-mediated photosensitization activates transcription factor NF-kappaB through the interleukin-1 receptor-dependent signaling pathway.

Pyropheophorbide-a methyl ester (PPME) is a second generation of photosensitizers used in photodynamic therapy. We demonstrated that PPME photosensitization activated NF-kappaB transcription factor in colon cancer cells. Unexpectedly, this activation occurred in two separate waves, i.

[Drug clinics. How I treat. II. Therapeutic approaches to metastatic colorectal cancer].

Since its introduction in 1953, 5-fluorouracil based chemotherapy remained the standard treatment in advanced colorectal cancer. Continuous infusion or biochemical modulation by folinic acid enhanced the therapeutic efficacy of this agent. Quality of life is limited by the toxicity of these regimens as well as by the frequent visits to the hospital during each cycle.

[Treatment of colorectal cancer. Pharmaco-economic aspects].

Cancer patients care is mainly based on scientific studies, but sometimes approaches are empiric. Rapid growth of health care expenses force the physician to take pharmacoeconomic aspects into consideration. New clinical studies have to analyse clinical benefits but also cost-effectiveness.

Regulation of major histocompatibility complex class I expression by NF-kappaB-related proteins in breast cancer cells.

Downregulation of MHC Class I antigens has been observed in many cancers and usually results from a decreased gene transcription. A reporter CAT gene dependent on the MHC Class I kappaB site or on a longer promoter is transactivated by NF-kappaB complexes containing p65 or RelB. p100 as well as IkappaB-alpha are potent inhibitors of this transcription and p100 sequesters RelB and p65 complexes in the cytoplasm of breast cancer cells.

[How I treat colorectal cancer. I. Prevention and adjuvant treatment].

Colorectal adenocarcinoma is a major cause of cancer-related morbidity and mortality in Belgium and in other western countries. Prevention implies a modification of alimentation and maybe a chronic uptake of acetylsalicylic acid. Treatment of colorectal cancers is based on surgery and the prognosis is determined by the locoregional or metastatic tumor spread.

Activation of the human immunodeficiency virus long terminal repeat by varicella-zoster virus IE4 protein requires nuclear factor-kappaB and involves both the amino-terminal and the carboxyl-terminal cysteine-rich region.

Varicella-zoster virus open reading frame 4-encoded protein (IE4) possesses transactivating properties for varicella-zoster virus genes as well as for those of heterologous viruses such as the human immunodeficiency virus type 1 (HIV-1). Mechanisms of HIV-1 LTR (long terminal repeat) transactivation were investigated in HeLa cells transiently transfected with an IE4 expression plasmid and a CAT reporter gene under the control of the HIV-1 LTR. These results demonstrated that IE4-mediated transactivation of the HIV-1 LTR in HeLa cells required transcription factor kappaB (NF-kappaB).

Distinct signal transduction pathways mediate nuclear factor-kappaB induction by IL-1beta in epithelial and lymphoid cells.

We previously demonstrated that IL-1beta-mediated induction of the nuclear factor-kappaB (NF-kappaB) transcription factor proceeds through the production of reactive oxygen intermediates in lymphoid cells, while it occurs independently of any oxidative stress in epithelial transformed cells. Indeed, inhibition of receptor internalization as well as NH4Cl and chloroquine blocked IL-1beta-mediated induction of NF-kappaB in OVCAR-3 and in other epithelial cell lines but not in lymphoid cells, indicating that distinct pathways are involved. Conversely, while we observed phospholipase A2 activity in both cell types following IL-1beta stimulation, specific inhibitors of this enzyme inhibited NF-kappaB induction only in lymphoid cells.

Nuclear factor - kappaB-dependent regulation of p53 gene expression induced by daunomycin genotoxic drug.

Anthracycline drugs are widely used for the treatment of solid tumors and leukemia, but the molecular basis of their biological effect is still poorly understood. In the HCT116 colon carcinoma cell line, which retains a wild-type inducible p53 gene, we show that the anthracycline daunomycin is a potent inducer of p53 and NF-kappaB transcription factors. Nuclear accumulation of p53 protein occurred because of increased protein stability and enhanced gene expression.

Multiple redox regulation in NF-kappaB transcription factor activation.

The well-known Rel/NF-kappaB family of vertebrate transcription factors comprises a number of structurally related, interacting proteins that bind DNA as dimers and whose activity is regulated by subcellular location. This family includes many members (p50, p52, RelA, RelB, c-Rel, ..