Search

AIMS We aimed to assess the optimal management of first or later-line lenvatinib therapy (LEN) for patients with unresectable hepatocellular carcinoma (uHCC), by clarifying the difference of degree between relative dose intensity (RDI) to achieve objective response (OR) and disease control (DC) by aiming at stable disease (SD), taking dose modifications into consideration. METHODS One hundred uHCC patients who received LEN in first- or later-line settings, between April 2018 and December 2020 in our hospital were analyzed retrospectively. The factors associated with overall survival (OS), time to progression (TTP), OR and DC were assessed. The optimal cut-off values of RDI 4 weeks after initiation of LEN (RDI during cycle 1) and total RDI (RDI during all cycles) to predict achievement of OR and DC by aiming at SD were determined by receiver operator curve analysis. RESULTS Achievement of OR and SD were favorable factors for OS (HR, 0.080 and 0.20) and TTP (HR, 0.052 and 0.073), with progressive disease defined as the reference. RDI ≥ 0.8 during cycle 1 and RDI ≥ 0.4 during cycle 1 contributed to achievement of OR (odds ratio, 3.28) and DC (odds ratio, 4.85), respectively. Experience of dose interruption was associated with a favorable TTP (HR, 0.58). The therapeutic line of LEN did not contribute to OS, TTP or best response. CONCLUSIONS To achieve OR and SD for a favorable outcome of first- or later-line LEN, high and moderate early-phase RDI are required, respectively. The degree of RDI during LEN and tolerance need compatible by dose modifications.

A 23-year-old nulliparous woman, a hepatitis B virus (HBV) carrier with stable liver functions, presented with exacerbation of viral replication (HBV DNA level >9.0 log copies/mL) in gestational week 26. During the subsequent follow up without antiviral therapy, she was hospitalized with progression to hepatic failure in gestational week 35. Following initiation of antiviral therapy with lamivudine, emergent cesarean delivery was conducted for fetal safety. Liver atrophy and persistent hepatic encephalopathy (stage 2) necessitated artificial liver support (ALS) involving online hemodiafiltration (HDF) and plasma exchange. She regained full consciousness after the sixth online HDF session. ALS was terminated after the seventh online HDF session. On day 33 of hospitalization, she was discharged home without sequelae. Genetic analysis of the HBV strain isolated from her serum showed that this strain had genotype C. Direct full-length sequencing identified no known mutations associated with fulminant hepatitis B. HBV-related hepatic failure observed in the present case might have been related to perinatal changes in the host immune response.

The aim of this study was to investigate the effect of dietary lemon polyphenols on high-fat diet-induced obesity in mice, and on the regulation of the expression of the genes involved in lipid metabolism to elucidate the mechanisms. Mice were divided into three groups and fed either a low fat diet (LF) or a high fat diet (HF) or a high fat diet supplemented with 0.5% w/w lemon polyphenols (LP) extracted from lemon peel for 12 weeks. Body weight gain, fat pad accumulation, the development of hyperlipidemia, hyperglycemia, and insulin resistance were significantly suppressed by lemon polyphenols. Supplementation with lemon polyphenols also significantly up-regulated the mRNA level of the peroxisome proliferator activated receptor-alpha (PPARalpha) compared to the LF and HF groups in the liver. Furthermore, the mRNA level of acyl-CoA oxidase (ACO) was up-regulated in the LP group compared to the LF group, but not HF group in the liver, and was also significantly increased in the epididymal white adipose tissue. Thus, feeding with lemon polyphenols suppressed body weight gain and body fat accumulation by increasing peroxisomal beta-oxidation through up-regulation of the mRNA level of ACO in the liver and white adipose tissue, which was likely mediated via up-regulation of the mRNA levels of PPARalpha.

AIM: To investigate the acute effects of postprandial exercise on glucose and lipoprotein metabolism after the intake of glucose with or without fat cream in healthy but sedentary young women. METHODS: Healthy young Japanese women with a sedentary lifestyle, normal weight (18.5≤BMI

Aim: To compare the acute effects of shortly pre- vs. postprandial exercise on postprandial lipid metabolism in healthy but sedentary young Japanese women.Methods: Healthy young Japanese women with a sedentary lifestyle, normal weight (18.5 ≤ BMI < 25), normal ovarian cycle, and apolipoprotein E3/3 were selected as participants. A single bout of walking exercise was performed 20 min after (Exp. 1) or 50 min before (Exp. 2) the intake of oral fat tolerance test (OFTT) cream (1 g/kg body weight) at about 50% Vo2max for 30 min on a motorized treadmill. A control trial without exercise was also performed in each experiment. Each subject performed 2 trials in a randomized, cross-over design. Venous blood samples were drawn before the preprandial exercise (−1 h, Exp. 1 only) and before (0 h) and 1, 2, 4 and 6 h after the fat intake for the determination of triglyceride (TG), apolipoprotein B-48 (apoB48), remnant-like particle-TG (RLP-TG), lactate, free fatty acid (FFA), insulin, and glucose.Results: In both experiments, postprandial serum TG concentrations in the exercise group were lower, but not significantly, than those in the control. In Exp. 1, incremental areas under the curve (IAUC) for TG and RLP-TG were slightly, but not significantly, smaller in the postprandial exercise group than the control. The values of apoB48, a marker of the chylomicron particle number, at 2, 4, and 6 h after the fat intake and IAUC for apoB48 were significantly lower in the postprandial exercise group than the control. In Exp. 2, IAUC for TG, RLP-TG, and apoB48 were not significantly different between the two groups.Conclusion: The present findings suggest that postprandial, but not preprandial, exercise may reduce the number of chylomicrons and chylomicron remnants and improve exogenous lipoprotein metabolism. Postprandial exercise is more effective for improving postprandial lipoprotein metabolism than preprandial exercise.

Background Obesity, especially visceral obesity, has been known to affect lipoprotein metabolism, but it is not clear whether obesity in young, apparently healthy men is associated with postprandial triglyceride-rich lipoprotein (TRL) metabolism. Methods Ten young normolipidemic, normoglycemic obese men (20.6 ± 0.5 y, BMI 27.5 ± 1.0 kg/m 2 ) and 11 lean healthy men (22.1 ± 0.4 y, 21.2 ± 0.4 kg/m 2 ) ingested OFTT cream (1 g/kg body weight). Fasting and postprandial blood samples were obtained for up to 6 h, and serum lipids and lipoproteins were analyzed. Results The obese men with a fasting triglyceride (TG) in the normal range and not different from the fasting value of lean controls had a prolonged postprandial response, indicated by a significantly greater incremental areas under the curve in serum TG, TRL-TG, and remnant-like particle-cholesterol (RLP-C) compared with controls. Plasma glucose levels did not change during the test. Differences in serum insulin levels and homeostasis model assessment-insulin resistance (HOMA-IR) were not statistically significant between the two groups; however, trends toward higher levels were shown in obese young men. Conclusions The obese young men showed significantly delayed TRL metabolism compared to the lean young men after fat loading, even though the obese men were normolipidemic. These results suggest the possibility that early insulin resistance in the obese young men may have caused the decrease of lipoprotein lipase activity and induced delayed TRL metabolism. A fat loading test without carbohydrate may provide a useful tool for the detection of delayed postprandial TRL metabolism and early insulin resistance.

A tyrosine kinase adaptor protein containing pleckstrin homology and SH2 domains (APS) is rapidly and strongly tyrosine phosphorylated by insulin receptor kinase upon insulin stimulation. The function of APS in insulin signaling has heretofore remained unknown. APS -deficient ( APS −/− ) mice were used to investigate its function in vivo. The blood glucose-lowering effect of insulin, as assessed by the intraperitoneal insulin tolerance test, was increased in APS −/− mice. Plasma insulin levels during fasting and in the intraperitoneal glucose tolerance test were lower in APS −/− mice. APS −/− mice showed an increase in the whole-body glucose infusion rate as assessed by the hyperinsulinemic-euglycemic clamp test. These findings indicated that APS −/− mice exhibited increased sensitivity to insulin. However, overexpression of wild-type or dominant-negative APS in 3T3L1 adipocytes did not affect insulin receptor numbers, phosphorylations of insulin receptor, insulin receptor substrate-1, or Akt and mitogen-activated protein kinase. The glucose uptake and GLUT4 translocation were not affected by insulin stimulation in these cells. Nevertheless, the insulin-stimulated glucose transport in isolated adipocytes of APS −/− mice was increased over that of APS +/+ mice. APS −/− mice also showed increased serum levels of leptin and adiponectin, which might explain the increased insulin sensitivity of adipocytes.