oxazolone and Neoplasms

T helper type 2 (Th2)-characterized inflammatory responses are highly dynamic processes initiated by epithelial cell damage resulting in remodelling of the tissue architecture to prevent further harm caused by a dysfunctional epithelial barrier or migrating parasites. This process is a temporal and spatial response which requires communication between immobile cells such as epithelial, endothelial, fibroblast and muscle cells and the highly mobile cells of the innate and adaptive immunity. It is further characterized by a high cellular plasticity that enables the cells to adapt to a specific inflammatory milieu. Incipiently, this milieu is shaped by cytokines released from epithelial cells, which stimulate Th2, innate lymphoid and invariant natural killer (NK) T cells to secrete Th2 cytokines and to activate dendritic cells which results in the further differentiation of Th2 cells. This milieu promotes wound-healing processes which are beneficial in parasitic infections or toxin exposure but account for increasingly dysfunctional vital organs, such as the lung in the case of asthma and the colon in ulcerative colitis. A better understanding of the dynamics underlying relapses and remissions might lead ultimately to improved therapeutics for chronic inflammatory diseases adapted to individual needs and to different phases of the inflammation.

Topics: Animals; Cellular Microenvironment; Chronic Disease; Disease Models, Animal; Humans; Inflammation; Neoplasms; Oxazolone; Th2 Cells

A facile method via 1,3-dipolar cycloaddition of substituted benzylidene-2-phenyloxazolone under mild conditions with azomethine ylides, which were generated in situ by a decarboxylative route from a common set of diverse isatins and amino acid derivatives was developed for a 15-membered library of regio- and stereoselective oxazolones-grafted spirooxindole-pyrrolidine, pyrrolizidines and pyrrolothiazoles. After screening their cytotoxic activities against a spectrum of cell-lines, compound 4h was identified as potent antitumor agent and inducing apoptosis. The present study has provided an effective entry to rapidly construct a chemical library of oxazolones-grafted spirooxindoles and developed a good lead compound for subsequent optimization.

Topics: Antineoplastic Agents; Azo Compounds; Benzylidene Compounds; Cell Line, Tumor; Cycloaddition Reaction; Drug Discovery; Humans; Indoles; Models, Molecular; Neoplasms; Oxazolone; Oxindoles; Pyrrolidines; Spiro Compounds; Stereoisomerism; Thiosemicarbazones

Following the intraperitoneal injection of cis-diamino-dichloro-platinum (II) (CDDP) into tumor-bearing mice, two immune responses were augmented. The total splenic plaque-forming cells response to sheep red blood cells and the delayed-type hypersensitivity reaction to oxazolone were higher in treated animals than in the control groups. This observation may be relevant in the establishment of clinical protocols associating CDDP and other cytotoxic drugs.

Topics: Animals; Antibody Formation; Cisplatin; Erythrocytes; Hemolytic Plaque Technique; Hypersensitivity, Delayed; Mice; Neoplasms; Oxazolone; Sheep

A murine model of delayed cutaneous hypersensitivity has been used to study an effect of microwave whole-body hyperthermia on the immune system. Marked suppression of immune responsiveness was observed in mice exposed to repeated sessions of hyperthermia. Cell proliferation in regional lymph nodes of mice sensitized with oxazolone was significantly impaired as measured by uptake of 125I-iododeoxyuridine (125IUdR). The proportion of theta-positive cells and the total number of lymph node lymphocytes remained unchanged. Inhibition of proliferation of lymph node lymphocytes in vivo was accompanied by a decrease in mitogen-induced stimulation of lymphocytes in vitro. In particular the phytohaemagglutinin (PHA) response of T cells was affected by hyperthermia. It is concluded that whole-body hyperthermia can be a potent immunosuppressive factor.

Topics: Animals; Hot Temperature; Hypersensitivity, Delayed; Hyperthermia, Induced; Immunosuppression Therapy; Lymph Nodes; Lymphocyte Activation; Male; Mice; Mice, Inbred BALB C; Neoplasms; Oxazoles; Oxazolone; Skin; T-Lymphocytes