ABSTRACT
OBJECTIVES: Elevated albumin (ALB) mRNA concentration has been reported in the plasma of patients with liver diseases. The plasma ALB mRNA measurement was shown to be an effective indicator of liver pathologies with superior diagnostic sensitivity and specificity when compared with alanine transaminase (ALT). We hypothesized that serial plasma ALB mRNA analysis would be helpful in the early detection and monitoring of post-liver transplantation complications. DESIGN AND METHODS: One hundred and five blood specimens were collected from 24 post-transplant recipients. Biochemical liver function test profiles and plasma ALB mRNA concentrations were assessed. RESULTS: Over the study period, the health status of 14 recipients (58%) remained stable (Stable group). Their plasma ALB mRNA concentrations remained within a low-concentration range. In contrast, 10 recipients (42%) developed 14 episodes of hepatic complications (Unstable group). The median plasma ALB mRNA concentration of the Unstable group was 6.5-times higher than that of the Stable group. Plasma ALB mRNA concentration was elevated on 13/14 (93%) episodes of the hepatic complications while ALT was elevated only on 8/14 (57%) episodes. CONCLUSIONS: The elevation of plasma ALB mRNA may allow sensitive detection of hepatic complications and monitoring of the clinical course in a dynamic fashion. Serial plasma ALB mRNA measurement is potentially useful for post-liver transplantation management.
Subject(s)
Cholangitis/blood , Graft Rejection/blood , Liver Transplantation/adverse effects , Liver/metabolism , RNA, Messenger/blood , Serum Albumin/metabolism , Adolescent , Adult , Aged , Alanine Transaminase/blood , Biomarkers/blood , Carcinoma, Hepatocellular/surgery , Carcinoma, Hepatocellular/therapy , Cholangitis/etiology , Cholangitis/pathology , Female , Gene Expression , Graft Rejection/pathology , Humans , Liver/pathology , Liver Cirrhosis/surgery , Liver Cirrhosis/therapy , Liver Failure/surgery , Liver Failure/therapy , Liver Function Tests , Liver Neoplasms/surgery , Liver Neoplasms/therapy , Male , Middle Aged , Prognosis , RNA, Messenger/genetics , Sensitivity and Specificity , Serum Albumin/geneticsABSTRACT
The 'one pot' condensation reaction for the synthesis and potent antiproliferative inhibition of alpha-phthalimide based ketones is reported here. 2-Phthalimide-1-(4-fluoro-phenyl)ethanone (5) showed the best growth inhibition on human MDAMB-231 breast carcinoma and SKHep-1 hepatoma cell lines. Preliminary studies showed that the reported bioactivity may be due to the presence of strong electronegative fluorine group at the para-position of the aryl ring.
Subject(s)
Ketones/chemical synthesis , Ketones/pharmacology , Neoplasms/pathology , Phthalimides/chemistry , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Humans , Ketones/chemistry , Molecular Structure , Stereoisomerism , Structure-Activity Relationship , Tumor Cells, CulturedABSTRACT
Phthalic anhydride is a highly toxic substance, facing, however, the problem of hydrolysis. In fact, it is rapidly hydrolyzed in aqueous medium, generating phthalic acid as the final product, which is almost harmless to viable cells. Here we describe the 'one pot' condensation reaction for the synthesis of phthalic imide derivative (benzothiazole containing phthalimide), exhibiting in vitro cytotoxic potential on human cancer cell lines. We further demonstrated that both caspase-dependent and -independent pathways are involved in our novel benzothiazole containing phthalimide induced apoptosis on cancer cells.
