Obesity conveys poor outcome in patients with hepatocellular carcinoma treated by transarterial chemoembolization.

PURPOSE: The purpose of this retrospective study was to evaluate the impact of obesity on radiologic outcomes in patients with hepatocellular carcinoma (HCC) treated by transarterial chemoembolization (TACE). MATERIALS AND METHODS: A total of 100 TACE procedures performed in 57 patients (42 men, 15 women) with a mean age of 62 years±8.4 (SD) (range: 39-83 years) were retrospectively reviewed. The 1-2-month follow-up computed tomography or magnetic resonance imaging examinations was assessed for new or residual disease and radiologic response using mRECIST criteria. Patients were categorized into two groups according to body mass index (BMI). Patients with BMI<25kg/m2 were further referred as to low BMI patients and those with BMI≥25kg/m2 as high BMI patients. Outcomes were compared between the two groups. RESULTS: Low and high BMI patients were similar in regard to age, gender, HCC etiology and stage, and pre-procedure disease burden. TACE for high BMI, compared to low BMI, patients resulted in lower complete response (39% vs. 66%) and higher progressive disease (21% vs. 5%) rates (P=0.04), and higher rates of residual disease (63% vs. 39%, P=0.02) and new lesions in untreated liver (39% vs. 18%, P=0.04) on 1-2-month follow-up imaging. CONCLUSIONS: High BMI is associated with significantly more residual disease, new lesions, and progressive disease in patients with HCC treated by TACE.

Carboxylesterase isoenzyme specific deacylation of diacetoxyscirpenol (anguidine).

The deacylation reaction of diacetoxyscirpenol (DAS), a trichothecene mycotoxin, was studied by using five carboxylesterase isoenzymes isolated from mouse liver microsomes. The simultaneous isolation of the five microsomal carboxylesterase isoenzymes was accomplished by chromatofocusing. DAS serves as a unique substrate since both acetyl groups are accessible for hydrolysis, providing an opportunity to investigate the regioselective hydrolysis of DAS with the various isoenzymes. A novel basic carboxylesterase isoenzyme, pI 8.4-8.2, was isolated. This isoenzyme exhibits strict regioselectivity toward DAS hydrolysis; only the acetyl group at C-4, but not that at C-15, is hydrolyzed. Moreover, this is the major isoenzyme responsible for the deacylation of DAS in mouse hepatic microsomes. The rate constant determined for deacylation of DAS at C-4 for this isoenzyme is 130-1000 times greater than that of the other carboxylesterases. This isoenzyme was also the most efficient for the hydrolysis of 4-monoacetoxyscirpenediol with a rate constant 30-100 times greater than that of the other isoenzymes.

Chiral instability at sulfur of S-adenosylmethionine.

S-Adenosylmethionine, generated enzymically in chirally pure form (S configuration at sulfur), undergoes simultaneous irreversible conversion to 5'-deoxy-5'-(methylthio)adenosine and homoserine with a rate constant of 6 X 10(-6) s-1 at pH 7.5 and 37 degrees C and reversible conversion to an enzymically inactive stereoisomer (R configuration at sulfur) with a forward rate constant of 8 X 10(-6) s-1 at pH 7.5 and 37 degrees C. These forms of instability require small turnover times and/or stabilization through macromolecular binding for S-adenosylmethionine, if organisms that utilize it are to avoid losses of metabolic energy.

Phenol sulfotransferase. II. Inactivation by phenylglyoxal, N-ethylmaleimide and ribonucleotide 2',3'-dialdehydes.

Phenylglyoxal, a chemical modifying agent for arginine residues, produced rapid inactivation of a rat liver phenol sulfotransferase (3-phosphoadenylylsulfate:phenol sulfotransferase, EC 2.8.2.1). Enzyme inactivation was accompanied by incorporation of 1.5 mol [7-14C]phenylglyoxal per mol enzyme. 3'-Phosphoadenosine 5'-phosphosulfate (PAPS), the sulfate donor, prevented inactivation and decreased [7-14C]phenylglyoxal incorporation to 0.78 mol/mol enzyme. The sulfhydryl-modifying agent, N-ethylmaleimide, also caused rapid inactivation of phenol sulfotransferase with concomitant incorporation of 2.35 mol N-[3H]ethylmaleimide per mol enzyme. These results suggest a possible role for arginine residues as anionic recognition sites for the sulfate donor PAPS, and indicate the presence of essential sulfhydryl residues on phenol sulfotransferase. Ribonucleotide dialdehydes (ATPDA, ADPDA, AMPDA, APSDA), but not the corresponding 2',3'-acyclic nucleotides (ATPDO, ADPDO, AMPDO, APSDO), produced rapid and irreversible inactivation of phenol sulfotransferase. These ribonucleotide dialdehydes appear to modify the active site of the enzyme, since inclusion of the sulfate donor, PAPS, or the product, adenosine 3',5'-bisphosphate (PAP), in the incubation mixture prevented loss of enzyme activity. In contrast, the sulfate acceptor, p-nitrophenol, did not show similar protective effects. Kinetic studies indicated that the ribonucleotide dialdehydes inactivated the enzyme via a unimolecular reaction within a dissociable enzyme-inhibitor complex rather than via a nonspecific bimolecular process. Radioactively labeled ribonucleotide dialdehydes (e.g.,[2, 8-3H]ATP) were incorporated into protein concomitant with loss of enzyme activity. The incorporated ligand could be removed by dialysis in phosphate or Tris buffer. The protein-ligand complex could be stabilized to dialysis by pretreatment with sodium borohydride. The results of these studies suggest that ribonucleotide dialdehydes are affinity labeling reagents for phenol sulfotransferase, causing enzyme inactivation by the possible formation of a Schiff base adduct with an active-site lysine residue.