Overexpression of cyclooxygenase-2 and transforming growth factor-beta 1 is an independent predictor of poor virological response to interferon therapy in chronic HCV genotype 4 patients.

BACKGROUND/AIMS: COX-2 and TGF-ß1 are overexpressed in hepatitis C virus (HCV) infection and are related to hepatitis pathogenesis and hepatic fibrosis. The current study investigated the relationship between pretreatment COX-2 and TGF-ß1 hepatic expression in HCV genotype 4 and the virological response to interferon therapy. PATIENTS AND METHODS: Liver biopsies of 55 patients with HCV infection genotype 4 were selected together with 10 liver biopsies as control. The patients' clinicopathological data were collected. Immunohistochemistry was done using anti-COX-2 and anti-TGF-ß1 antibodies. Statistical tests were used to determine the association between both COX-2 and TGF-ß1 expression in relation to clinicopathological parameters and response to interferon therapy. RESULTS: COX-2 was upregulated especially in nonresponders and was an independent predictor of poor virological response. However, COX-2 showed no association with other clinicopathological features. TGF-ß1 was upregulated and associated with nonresponders, histological activity, and fibrosis stage. There was no association between TGF-ß1 and other clinicopathological features. There was an association between COX-2 and TGF-ß1 immunoexpression. CONCLUSION: Overexpression of COX-2 and TGF-ß1 is an independent predictor for poor outcome of interferon and ribavirin therapy and these might be useful markers for the response to treatment. Both molecules are associated together; however, their role during hepatitis treatment has to be clarified.

Ewing`s sarcoma family tumors in the western region of Saudi Arabia. A pathological experience from 2 tertiary medical centers.

OBJECTIVE: To review the pattern of Ewing`s sarcoma/primitive neuroectodermal tumor (ES/PNET) in 2 medical centers in the western region of Saudi Arabia. METHODS: We retrospectively analyzed the pathological data of patients diagnosed with ES/PNET in 2 tertiary medical centers in the western region of Saudi Arabia (King Abdulaziz University Hospital, [March 1995 to November 2011], and King Faisal Specialized Hospital [April 2003 to 12 December 2010]). Age, gender, and site of tumors were analyzed. RESULTS: Sixty-nine cases were diagnosed as ES/PNET. The age range was 3-62 years (mean 22 years). Male cases were more than the female. Approximately 28.9% of cases presented within the skeleton, and 71.1% cases were presented as a soft tissue disease. Bone affection was higher in the iliac bone. Long bones were affected at a lower frequency. Soft tissue affection showed a higher incidence in the head and neck region followed by the lower limb. CONCLUSION: The current study represents a review of a large number of Ewing`s sarcoma family of tumors in western Saudi Arabia. Cases showed clinicopathological features comparable to those reported from other locations worldwide apart from relatively higher soft tissue affection than skeletal affection and a higher incidence of head and neck involvement by soft tissue ES/PNET. Further, multicenter studies (epidemiological and genetic) are recommended to obtain profiling of the disease and effect on outcome and therapy.

Effect of selective and non-selective cyclooxygenase inhibitors on doxorubicin-induced cardiotoxicity and nephrotoxicity in rats.

CONTEXT: Doxorubicin (DX) is a highly effective chemotherapeutic agent used widely in the treatment of solid tumors; however, its optimal use was associated with cardiotoxicity and nephrotoxicity. The exact mechanism of DX-induced cardiotoxicity and nephrotoxicity is not fully explored. Induction of cyclooxygenase-2 (COX-2) activity in either cardiac or renal tissue by DX has been previously reported, indicating a possible role of COX-2 in DX-induced tissue injury. However, the nature of this role in either tissue injury is an issue of controversy. OBJECTIVE: This study was the first that simultaneously evaluated the effects of a selective COX-2 inhibitor, nimesulide, and a non-selective COX-inhibitor, indomethacin, on DX-induced cardiotoxicity and nephrotoxicity in male Wistar rats. MATERIALS AND METHODS: Rats were allocated into four groups. Control group, DX group (received 15 mg/kg, ip), DX + nimesulide (10 mg/kg/day, po) group, and DX + indomethacin (2 mg/kg/day, po) group. Nimesulide and indomethacin were started at the same day of DX injection and continued for 5 days. RESULTS: The results of the present study showed that inhibition of COX-2 either by selective or non-selective COX-2 inhibitor ameliorated DX-induced cardiotoxicity but aggravated DX-induced nephrotoxicity in rats, as evidenced biochemically and histopathologically. DISCUSSION AND CONCLUSION: Our study indicates that production of COX-2 is organ specific; consequently, the differential effect of COX-inhibitors should be considered in DX-treated patients. However, a wide scale experiment is needed for further confirmation and testing other members of COX-inhibitors (e.g. celecoxib and diclofenac).