Biomedical subjects

P Michaluart

Publications and source records attributed to P Michaluart.

5 recordsLinked to original sources

PubMed2000

Ursolic acid inhibits cyclooxygenase-2 transcription in human mammary epithelial cells.

We investigated the effects of ursolic acid, a chemopreventive agent, on the expression of cyclooxygenase-2 (COX-2) in phorbol 12-myristate 13-acetate (PMA)-treated human mammary and oral epithelial cells. Treatment with ursolic acid suppressed PMA-mediated induction of COX-2 protein and synthesis of prostaglandin E2. Ursolic acid also suppressed the induction of COX-2 mRNA by PMA. Nuclear run-offs revealed increased rates of COX-2 transcription after treatment with PMA, an effect that was inhibited by ursolic acid. Transient transfections indicated that the effects of PMA were mediated by a cyclic AMP response element in the COX-2 promoter. Ursolic acid inhibited PMA-mediated activation of protein kinase C, extracellular signal-regulated kinase 1/2, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinases. Treatment with PMA increased activator protein-1 activity and the binding of c-Jun to the cyclic AMP response element of the COX-2 promoter, effects that were blocked by ursolic acid. These data are important for understanding the anticancer and anti-inflammatory properties of ursolic acid.

Blotting, Northern↗

PubMed1999

Inhibitory effects of caffeic acid phenethyl ester on the activity and expression of cyclooxygenase-2 in human oral epithelial cells and in a rat model of inflammation.

We investigated the mechanisms by which caffeic acid phenethyl ester (CAPE), a phenolic antioxidant, inhibited the stimulation of prostaglandin (PG) synthesis in cultured human oral epithelial cells and in an animal model of acute inflammation. Treatment of cells with CAPE (2.5 microg/ml) suppressed phorbol ester (12-O-tetradecanoylphorbol-13-acetate; TPA) and calcium ionophore (A23187)-mediated induction of PGE2 synthesis. This relatively low concentration of CAPE did not affect amounts of cyclooxygenase (COX) enzymes. CAPE nonselectively inhibited the activities of baculovirus-expressed hCOX-1 and hCOX-2 enzymes. TPA- and A23187-stimulated release of arachidonic acid from membrane phospholipids was also suppressed by CAPE (4-8 microg/ml). Higher concentrations of CAPE (10-20 microg/ml) suppressed the induction of COX-2 mRNA and protein mediated by TPA. Transient transfections using human COX-2 promoter deletion constructs were performed; the effects of TPA and CAPE were localized to a 124-bp region of the COX-2 promoter. In the rat carrageenan air pouch model of inflammation, CAPE (10-100 mg/kg) caused dose-dependent suppression of PG synthesis. Amounts of COX-2 in the pouch were markedly suppressed by 100 mg/kg CAPE but were unaffected by indomethacin. These data are important for understanding the anticancer and anti-inflammatory properties of CAPE.

Air↗

PubMed1999

Resveratrol inhibits cyclooxygenase-2 transcription in human mammary epithelial cells.

A large body of evidence suggests that inhibiting cyclooxygenase-2 (COX-2), the inducible form of COX, will be an important strategy for preventing cancer. In this study, we investigated whether resveratrol, a chemopreventive agent found in grapes, could suppress phorbol ester (PMA)-mediated induction of COX-2 in human mammary and oral epithelial cells. Treatment of cells with PMA induced COX-2 mRNA, COX-2 protein, and prostaglandin synthesis. These effects were inhibited by resveratrol. Nuclear runoffs revealed increased rates of COX-2 transcription after treatment with PMA, an effect that was inhibited by resveratrol. Resveratrol inhibited PMA-mediated activation of protein kinase C and the induction of COX-2 promoter activity by c-Jun. Phorbol ester-mediated induction of AP-1 activity was blocked by resveratrol. These data are likely to be important for understanding the anticancer and anti-inflammatory properties of resveratrol.

Antineoplastic Agents, Phytogenic↗

PubMed1998

Resveratrol inhibits cyclooxygenase-2 transcription and activity in phorbol ester-treated human mammary epithelial cells.

We determined whether resveratrol, a phenolic antioxidant found in grapes and other food products, inhibited phorbol ester (PMA)-mediated induction of COX-2 in human mammary and oral epithelial cells. Treatment of cells with PMA induces COX-2 and causes a marked increase in the production of prostaglandin E2. These effects were inhibited by resveratrol. Resveratrol suppressed PMA-mediated increases in COX-2 mRNA and protein. Nuclear run-offs revealed increased rates of COX-2 transcription after treatment with PMA, an effect that was inhibited by resveratrol. PMA caused about a 6-fold increase in COX-2 promoter activity, which was suppressed by resveratrol. Transient transfections utilizing COX-2 promoter deletion constructs and COX-2 promoter constructs, in which specific enhancer elements were mutagenized, indicated that the effects of PMA and resveratrol were mediated via a cyclic AMP response element. Resveratrol inhibited PMA-mediated activation of protein kinase C. Overexpressing protein kinase C-alpha, ERK1, and c-Jun led to 4.7-, 5.1-, and 4-fold increases in COX-2 promoter activity, respectively. These effects also were inhibited by resveratrol. Resveratrol blocked PMA-dependent activation of AP-1-mediated gene expression. In addition to the above effects on gene expression, we found that resveratrol also directly inhibited the activity of COX-2. These data are likely to be important for understanding the anti-cancer and anti-inflammatory properties of resveratrol.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1998

Parathyroid carcinoma.

BACKGROUND: Parathyroid carcinoma is rare and represents 0.1% to 5% of the cases of hyperparathyroidism. New accounts are important to the understanding of these tumors. Experience in 9 cases is reported. METHODS: From 1970 to 1995, 10 patients with parathyroid carcinoma demonstrated by clinical course or pathologic features of malignancy were treated. The patient's clinical data, laboratory and imaging examinations, surgical findings, pathology, recurrences, and survival were analyzed. RESULTS: One male patient was excluded because of insufficient data. Average age was 51 years, with female:male ratio of 2:1. Average calcium level was 14,3 mg/dL. Palpable mass was found in 55%, bone disease in 89%, and renal disease in 78%. Four patients were reoperations. Five were operated on for hyperparathyroidism (1/tertiary). Capsular invasion was the most incident pathologic feature. Local recurrence occurred in 55%; neck node and bone metastasis in 11%, and lung in 33%. Two patients are alive and 5 died of disease. CONCLUSIONS: Parathyroid carcinoma has clinical and laboratory features that can help diagnosis at the first surgery. It seems to have variable malignancy.

Adenoma↗