A5000260833- Ubiquitin and proteasome pathways
- Immune Cell Function and Interaction
- Immune Response and Inflammation
- Multiple Myeloma Research and Treatments
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Monoclonal and Polyclonal Antibodies Research
- Cell death mechanisms and regulation
- Cell Adhesion Molecules Research
- Cancer Mechanisms and Therapy
- Cancer, Hypoxia, and Metabolism
- Chronic Lymphocytic Leukemia Research
- Glycosylation and Glycoproteins Research
- Neuropeptides and Animal Physiology
- Protein Degradation and Inhibitors
- CAR-T cell therapy research
- Histone Deacetylase Inhibitors Research
- Cancer-related Molecular Pathways
- TGF-β signaling in diseases
- Natural product bioactivities and synthesis
- Cytokine Signaling Pathways and Interactions
- Animal Nutrition and Physiology
- Peptidase Inhibition and Analysis
- Microbial infections and disease research
- Atrial Fibrillation Management and Outcomes
Bloomfield College
2020-2023
Experimental Medicine and Biology Institute
2023
Hadassah Medical Center
2023
Monmouth University
2003-2020
University of Connecticut
2020
Janssen (United States)
2020
Ospedali Riuniti di Ancona
2017
Marche Polytechnic University
2017
Azienda Ospedaliero Universitaria Ospedali Riuniti
2017
Ospedali Riuniti Marche Nord
2016
Modulation of the growth human and murine cell lines in vitro by recombinant tumor necrosis factor-alpha (rTNF-alpha) interferon-gamma (rIFN-gamma) was investigated. rTNF-alpha had cytostatic or cytolytic effects on only some lines. When administered together with rIFN-gamma, showed enhanced antiproliferative a subset tested. In contrast to its sensitive cells, augmented normal diploid fibroblasts. Variations proliferative response induced were apparently not due differences either number...
Recombinant human tumor necrosis factor (rTNF alpha) injected intravenously into rabbits produces a rapid-onset, monophasic fever indistinguishable from the produced by rIL-1. On weight basis (1 microgram/kg) rTNF alpha and rIL-1 produce same amount of induce comparable levels PGE2 in rabbit hypothalamic cells vitro; like IL-1, TNF is blocked drugs that inhibit cyclooxygenase. At higher doses (10 micrograms/kg) biphasic fevers. The first reaches peak elevation 45-55 min after bolus injection...
Recombinant human interferon-gamma (rHuIFN-gamma) and natural tumor necrosis factor beta (nHuTNF-beta) (previously called lymphotoxin), purified to homogeneity, were used assess their effects on certain functions of polymorphonuclear neutrophils (PMN) in vitro. The treatment PMN with 100 U either rHuIFN-gamma or nHuTNF-beta for 20 min significantly increased ability phagocytize 1.5-microns latex beads as detected by flow cytometry. Preparations recombinant TNF-beta (rHuTNF-beta) showed...
The individual roles of the murine type 1 and 2 tumor necrosis factor (TNF) receptors (TNF-R1 TNF-R2) were investigated utilizing (i) strong species specificity TNF-R2 for TNF compared to human (ii) agonistic rabbit polyclonal antibodies directed against receptors. Proliferation mouse thymocytes cytotoxic T-cell line CT-6 is stimulated by but not TNF. Consistent with this observation, induced proliferation in both these cell types, whereas TNF-R1 had no effect. In contrast, cytotoxicity LM...
The immunoregulatory effects of transforming growth factor beta (TGF-beta) and recombinant murine tumor necrosis alpha (rMuTNF-alpha) on CTL generation activity were examined. results demonstrate that TGF-beta, in a dose-dependent manner, inhibited but not activity. inhibitory detected only when TGF-beta was added within the first 48 h MLC. Little seen it thereafter, including addition to cytotoxicity assay. production TNF-alpha, which occurs during early phases MLC is presence appears have...
Human peripheral blood mononuclear cells (PBMC) were induced by recombinant interleukin 2 and mitogens to secrete two distinct cytotoxic polypeptides, tumor necrosis factor-alpha (TNF-alpha) factor-beta (TNF-beta), previously called lymphotoxin. Treatment of PBMC with human (rIL 2) or in combination interferon-gamma (rIFN-gamma) resulted augmented production both TNF-alpha TNF-beta. rIFN-gamma alone had no effect on either polypeptide. was produced within 3 hr after induction the major...
We investigated the ability of cyclosporin A (CsA) and transforming growth factor beta (TGF-beta) to modulate production TNF-alpha TNF-beta IFN-gamma by unseparated, nonadherent, adherent PBMC. Treatment unseparated PBMC with CsA resulted in a significant dose-dependent inhibition all three cytokines ranging from greater than 90% for TNF-beta, approximately 70% TNF-alpha. Pretreatment or nonadherent TGF-beta inhibited 60-70%. However, these cells was only minimally affected, at 0.1-1 ng/ml...
Interleukin 1 (IL-1) and tumor necrosis factor alpha are thought to contribute the inflammatory response associated with autoimmune diseases. Transforming growth beta (TGF-beta 1) counteracts many effects of these cytokines has various immunosuppressive properties. In present study, it is shown that microgram amounts TGF-beta 1, injected daily for 1-2 weeks, protect against collagen-induced arthritis (CIA) relapsing experimental allergic encephalomyelitis (REAE), animal models rheumatoid...
A murine tumor necrosis factor (MuTNF) cDNA was isolated from a library prepared by using mRNA the macrophage-like cell line PU5-1.8 induced with 4 beta-phorbol 12 beta-myristate 13 alpha-acetate. The encodes polypeptide consisting of 79 amino acid pre sequence followed mature MuTNF 156 acids. 235 pre-TNF is 79% homologous to human protein. There one potential N-linked glycosylation site on MuTNF, in contrast TNF, which lacks any such site. cDNA, when engineered for expression Escherichia...
Both tumor necrosis factor alpha (TNF-alpha) and transforming growth beta (TGF-beta) are found in synovial fluid from arthritic joints of humans rodents with experimental arthritis. The role endogenously produced TGF-beta TNF the pathogenesis collagen type II-induced arthritis (CIA) DBA/1 mice was examined by determining effect neutralizing monoclonal antibodies to these factors on course disease. Endogenously as well systemically administered 1 TNF-alpha had opposite effects, since anti-TNF...
We have examined the effects of transforming growth factor-beta (TGF-beta 1) on expression class II histocompatibility Ag, HLA-DR: induced by human rIFN-gamma (rHuIFN-gamma) in melanoma, Hs294T cells and 2) constitutively expressed a subclone cell line. The HLA-DR Ag was rHuIFN-gamma dose- time-dependent manner with maximal levels obtained 10 ng/ml after 48 h exposure. Treatment natural porcine platelet-derived or rTGF-beta 1 (1 to 100 ng/ml) presence (0.1 reduced percentage positive for...
TNF-alpha can enhance the proliferation of human thymocytes stimulated by comitogen Con A. To determine which two different TNF receptors is responsible for signaling this cellular response, we investigated in response to agonistic antibodies specific receptor types. In contrast previously examined activities cells, thymocyte was rabbit polyclonal directed against 75-kDa (TNF-R2), but not those 55-kDa (TNF-R1). Lymphotoxin (TNF-beta) also shown stimulate proliferation, demonstrating that...
Myocardial ischemia causes heart injury that is characterized by an increase in circulating tumor necrosis factor (TNF), the local production of superoxide anions, loss coronary vasodilation (relaxation) response to agents release endothelial cell relaxation factor, and cardiac tissue damage. Ischemic can be mimicked TNF. When given before or immediately after ischemic injury, transforming growth factor-beta (TGF-beta) reduced amount anions circulation, maintained endothelial-dependent...
Tumor necrosis factors (TNF) alpha and beta are structurally related cytokines that mediate a wide range of immunological, inflammatory, cytotoxic effects. During bacterial infection the bloodstream (sepsis), TNF-alpha induction by endotoxin is thought to be major factor contributing cardiovascular collapse critical organ failure can develop. Despite antibiotic therapy, these consequences sepsis continue have high mortality rate in humans. Here we describe potent TNF antagonist, receptor...
The diketopiperazine NPI-2358 is a synthetic analog of NPI-2350, natural product isolated from Aspergillus sp., which depolymerizes microtubules in A549 human lung carcinoma cells. Although structurally different the colchicine-binding site agents reported to date, binds tubulin. has potent in-vitro anti-tumor activity against various tumor cell lines and maintains with multidrug-resistant (MDR) profiles. In addition, when evaluated proliferating umbilical vein endothelial cells (HUVECs),...
Salinosporamide A (1, NPI-0052) is a potent proteasome inhibitor in development for treating cancer. In this study, series of analogues was assayed cytotoxicity, inhibition, and inhibition NF-kappaB activation. Marked reductions potency cell-based assays accompanied replacement the chloroethyl group with unhalogenated substituents. Halogen exchange cyclohexene ring epoxidation were well tolerated, while some stereochemical modifications significantly attenuated activity. These findings...
The interaction of highly purified recombinant human tumor necrosis factor-alpha (rTNF-alpha) with polymorphonuclear neutrophils (PMNs) was investigated. Binding 125I-rTNF-alpha to PMN reached maximum levels in 30 min at 37 degrees C and 2 h 4 C. Scatchard analysis competitive binding data indicated approximately 6000 receptor sites per cell a Kd 1.37 nM. rapid internalization rTNF-alpha. Following this receptor-mediated interaction, TNF-alpha found inhibit the migration PMNs under agarose...