thromboxane-b2 and Urinary-Bladder-Neoplasms

We have previously found increased expression of thromboxane synthase (TXAS) and thromboxane receptor (TP) beta isoform in the tissues of patients with bladder cancer. Studies in cell lines and mice have indicated a potential significant role of the thromboxane signaling pathway in the pathogenesis of human bladder cancer. This study was designed to determine if the changes observed in the tissues of patients with bladder cancer were mirrored by changes in the urine of these patients. We found increased levels of thromboxane B(2) (TXB(2)) the major metabolite of TXAS and increased levels of the TPβ receptor. These results raised the possibility that patients with bladder cancer may be followed for progression or remission of their disease by quantitation of these substances in their urine.

Topics: Biomarkers, Tumor; Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Gene Expression Regulation, Neoplastic; Humans; Protein Isoforms; Real-Time Polymerase Chain Reaction; Receptors, Thromboxane; Signal Transduction; Thromboxane B2; Thromboxane-A Synthase; United States; Urinary Bladder Neoplasms

The U937 monocytic cell line and its differentiated macrophage-like form have been well characterized, illustrating many similarities with their analogous in vivo cells. We examined the release of thromboxane B2 (TXB2) from undifferentiated and differentiated cells after stimulation with opsonized zymosan and investigated whether the release of this mediator could be modified by isoprenaline. After stimulation, the U937 cells released TXB2 in a dose-dependent manner, with the release greater from the differentiated cells. The TXB2 released was inhibited by flurbiprofen (> 10(-8) M; P < .01) and isoprenaline (> 10(-6) M; P < .01), and the inhibition was reversed by propranolol (10(-6) M; P < .02). Thus, it is clear that undifferentiated and differentiated U937 cells release TXB2, which can be inhibited by beta 2-adrenoceptor stimulation. These findings illustrate an important functional difference between the in vivo macrophages and differentiated U937 cells because beta 2-adrenoceptor stimulation does not inhibit mediator release from macrophages.

Topics: Cell Transformation, Neoplastic; Dose-Response Relationship, Drug; Flurbiprofen; Humans; Isoproterenol; Leukemia, Monocytic, Acute; Macrophages; Opsonin Proteins; Propranolol; Receptors, Adrenergic, beta; Thromboxane B2; Tumor Cells, Cultured; Urinary Bladder Neoplasms; Zymosan

The effects of haematoporphyrin-derivative-mediated photodynamic treatment on arachidonic acid metabolism and its relation to clonogenicity have been studied in human bladder-tumour cells. Photodynamic treatment resulted in a transient release of arachidonic acid-derived compounds; prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) especially were strongly increased. This release was reduced by chelation of intracellular Ca2+ with Quin-2 or by lowering the extracellular Ca2+ concentration in the medium with EGTA, presumably resulting in inhibition of phospholipase A2. A similar reduction was obtained when indomethacin, an inhibitor of the cyclo-oxygenase pathway, was added prior to light exposure. These three treatments enhanced the photosensitivity, as revealed by the clonogenicity assay. Incubation with PGE2 prior to light exposure, but not with TXB2, protected against reproductive-cell death. The results of these experiments suggest that Ca(2+)-mediated activation of cyclo-oxygenase, resulting in increased levels of PGE2, participates in a cellular-defence mechanism against photodynamic cell killing.

Topics: Calcium; Carcinoma, Transitional Cell; Cell Survival; Dinoprostone; Hematoporphyrin Derivative; Humans; Photochemotherapy; Thromboxane B2; Tumor Cells, Cultured; Urinary Bladder Neoplasms