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Expression of extracellular matrix metalloprotease inducer (EMMPRIN) in hepatocellular carcinoma
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Laminin-5 chains are expressed differentially in metastatic and nonmetastatic hepatocellular carcinoma
No full textClinical outcomes of bosentan in pulmonary arterial hypertension do not correlate with levels of TIMPs
No full textAbstract BACKGROUND: Matrix metalloproteinases (MMP) and their inhibitors, tissue inhibitors of metalloproteinases (TIMP), are involved in tissue inflammation and fibrotic processes. Treatment with bosentan has been shown to improve the clinical outcome of patients with pulmonary arterial hypertension (PAH) with and without association with systemic sclerosis (SSc), and also to modulate the serum levels of matrix metalloproteases-9. We measured TIMP-1 and TIMP-2 in the serum of patients with SSc with and without PAH treated with long-term bosentan compared with healthy donors (HD). MATERIALS AND METHODS: Serum samples from HD (n = 16) and patients with SSc (n = 35), including patients with SSc without PAH (n = 23) and patients with PAH (n = 12), were analyzed using enzyme-linked immunosorbent assays (ELISAs) for total TIMP-1 and TIMP-2. RESULTS: Both mean TIMP-1 and TIMP-2 levels were significantly increased in patients with SSc compared with HD, but no differences were observed between patients with SSc with and without PAH. In the eight bosentan-treated patients, TIMP-1 and TIMP-2 levels did not change during 1 year of treatment, while bosentan increased the 6-min walking distance by 136 meters after 1 year, as well as clinical outcomes. CONCLUSIONS: Increased levels of TIMP-1 and TIMP-2 in patients with SSc compared with HD suggest that the inhibition of proteolysis allows the accumulation of ECM proteins. As bosentan does not stimulate TIMPs, it appears to favour proteolytic imbalance and to increase the turnover of ECM proteins
Expression of extracellular matrix metalloprotease inducer (EMMPRIN) in hepatocellular carcinoma.
No full textThe effect of bosentan on matrix metalloproteinase-9 levels in patients with systemic sclerosis-induced pulmonary hypertension
No full textObjective Systemic sclerosis (SSc) is an autoimmune disease that can potentially involve all tissues and organs of the human body. Based on the extent of the disease and organ involvement, different subsets of patients and organ involvement, different subsets of patients have been identified and several classifications proposed have been identified and several classifications proposed aiming to better stratify affected patients. The occurrence aiming to better stratify affected patients. The occurrence of pulmonary arterial hypertension (PAH), characterized of pulmonary arterial hypertension (PAH), characterized by altered tissue remodelling of the entire vessel wall, is the most severe complication that influences prognosis and survival. The molecular basis underlying the vascular damage is not yet known, but a family of enzymes named matrix metalloproteinases (MMPs), with a proteolytic activity towards several extra-cellular matrix (ECM) components, is likely to be involved. Recently, a dual inhibitor of endothelin-1, bosentan, has been successfully evaluated in clinical trials in PAH patients.
RESEARCH DESIGN AND METHOD:
The aim of this study is to investigate the expression of MMP-2 and MMP-9 in the serum of different subsets of SSc patients, and in patients treated with bosentan. Thirty-five Caucasian patients with SSc were enrolled in the study, 12 of whom were found to have isolated PAH assessed by Doppler echocardiography. Eight patients fully met the inclusion criteria and were eligible for therapy with bosentan given at the dosage of 62.5 mg twice daily for 4 weeks followed by 125 mg twice daily for 50 weeks(15). The remaining patients (4/12) initiated bosentan therapy for a few weeks and, therefore, were considered at the baseline level only. Serum samples were analysed by gelatine zymography.
RESULTS:
The results suggest that MMP-9 but not MMP-2 is differently expressed according to the degree of organ involvement. In particular, MMP-9 serum levels are significantly decreased in PAH with respect to other subsets of SSc patients. Moreover, in bosentan-treated patients, after 12 months of therapy MMP-9 significantly (p < 0.05) increased and correlated with an improved clinical outcome, as measured by the '6-minutes walking' test.
CONCLUSIONS:
This is the first time that MMP-9 serum levels are reported to be down-regulated in PAH patients and up-regulated following bosentan treatment. Whether MMP-9 has a pathogenetic role in the vascular damage observed in PAH patients or it is a marker of bosentan effectiveness is not yet known. However, MMP-9 may be an important molecule that needs further investigation in SSc patients to better define its role
Laminin-5 chains are expressed differentially in metastatic and nonmetastatic hepatocellular carcinoma
No full textTransforming growth factor beta1 and soluble Fas serum levels in hepatocellular carcinoma
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