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Background:The efficacy of hepatic arterial infusion chemotherapy for the treatment of advanced hepatocellular carcinoma (HCC) remains unclear.Methods:The outcome of 476 patients with HCC who underwent hepatic arterial infusion chemotherapy with 5-fluorouracil and cisplatin (HAIC) were compared with 1466 patients who did not receive active therapy.Results:A survival benefit of the therapy after adjusting for known risk factors was observed (hazard ratio, 0.48; 95% CI, 0.41–0.56; P<0.0001). In propensity score-matched analysis (n=682), median survival time was longer for patients who underwent chemotherapy (14.0 months) than for patients who did not receive active treatment (5.2 months, P<0.0001).Conclusion:For advanced HCC, HAIC is considered to be an effective treatment.

Peroxisome proliferator-activated receptor a (PPARa) is a nuclear receptor that regulates the expression of genes associated with lipid metabolism. Recent studies have suggested that the expression of PPARa-dependent fibroblast growth factor 21 (FGF21) plays important roles in adaptation to fasting, such as lipolysis and ketogenesis. We found that a nighttime injection of bezafibrate, a ligand of PPARa, effectively induced FGF21 expression, whereas a daytime injection did not affect it. Furthermore, bezafibrate-induced circadian FGF21 expression was abolished in PPARa-deficient mice. These observations suggest that bezafibrate-induced circadian FGF21 expression is due to circadian variations in the responsiveness of the PPARa system in the liver.

Pancreatobiliary tract cancer is a highly fatal cancer. Detection of pancreatobiliary tract cancer is difficult because it lacks typical clinical symptoms and because of its anatomical location. Biomarker discovery is therefore important to detect pancreatobiliary tract cancer in its early stage. A study demonstrated that expression levels of miR‑1246, miR‑3976, miR‑4306, and miR‑4644 in serum exosomes were higher in pancreatic cancer patients than these levels in healthy control participants. Supposing that microRNA (miRNA) expression profiles in saliva are similar to those in serum, four miRNAs (miR‑1246, miR‑3976, miR‑4306, and miR‑4644) in salivary exosomes may also be useful for detection of pancreatobiliary tract cancer. In this study, it was examined whether these miRNAs could be used as biomarkers for pancreatobiliary tract cancer. Twelve pancreatobiliary tract cancer patients and 13 healthy control participants were analyzed as a cancer and a control group, respectively. Unstimulated whole saliva was collected, salivary exosomes were isolated, and total RNA was extracted. Using quantitative real‑time PCR (RT‑qPCR), the relative expression ratios of miR‑1246 and miR‑4644 were significantly higher in the cancer group than these ratios in the control group. Receiver operating characteristic (ROC) curves were constructed to analyze the discrimination power of these miRNAs. For miR‑1246, the results yielded an area under the curve (AUC) of 0.814 (P=0.008). For miR‑4644, the results yielded an AUC of 0.763 (P=0.026). For the combination of miR‑1246 and miR‑4644, the results yielded an increased AUC of 0.833 (P=0.005). This pilot study suggests that miR‑1246 and miR‑4644 in salivary exosomes could be candidate biomarkers for pancreatobiliary tract cancer.

SUMMARY Large numbers of apoptotic early diplotene oocytes were observed during the transition from ovary-like undifferentiated gonadal tissue to testes during sex differentiation in presumptive males of the zebrafish (Danio rerio). The percentage of terminal-deoxynucleotidyl-transferase-mediated dUTP nick-end labelling (TUNEL)-positive apoptotic oocytes in the gonads of presumptive males was approximately eight- to 12-fold higher than in genetic all-females. By 29 days post-hatching, all oocytes had disappeared from the gonads of presumptive males. In these males, we also observed apoptotic somatic cells in the ovarian cavity between 23 and 35 days post-hatching. Therefore, the disappearance of oocytes and the decomposition of the ovarian cavity caused by apoptosis during sex differentiation were male-specific events. In genetic all-females, apoptosis in a proportion of early diplotene oocytes was found in the undifferentiated gonads at 15–19 days post-hatching, probably as a result of programmed oocyte loss during ovarian development. These findings suggest that oocyte apoptosis is the mechanism of testicular and ovarian differentiation in zebrafish.

Background A histopathological assessment of left atrial appendages (LAA) resected during surgical treatment for atrial fibrillation (AF) was made, with the aim of improving the prediction of postoperative AF recurrence. Methods and ResultsThis clinicopathological study involved 57 surgical cases of valvular AF and 34 ageand sex-matched control autopsy cases with a history of sinus rhythm. LAA from the cases with valvular AF showed greater hypertrophy of cardiomyocytes (p<0.0001), greater nuclear enlargement (p<0.0001), more bizarre nuclei (BN; p<0.0001), and more intercellular fibrosis (ICF; p<0.001). Partial disarray of cardiomyocytes and fatty infiltration were recognized in both the AF and control groups. Thirty-seven cases had maintained sinus rhythm after surgery from 7 months to 10 years. AF recurred within a month of surgery in 17 and after a month in 3; there was no significant difference in histopathological features between them. These 20 cases had more cellular hypertrophy (p<0.025), nuclear enlargement (p<0.025), BN (p<0.01), and ICF (p<0.025) than those who maintained sinus rhythm after surgery. Conclusions The histopathological findings for LAA reflected the underlying valvular diseases; however, the most reliable predictors of postoperative AF recurrence were hypertrophy of cardiomyocytes, bizarre shaped nuclei, and extensive ICF. (Circ J 2007; 71: 70 -78)

Chronic viral hepatitis B and C and non-alcoholic fatty liver disease (NAFLD) have been widely acknowledged to be the leading causes of liver cirrhosis and hepatocellular carcinoma. As anti-viral treatment progresses, the impact of NAFLD is increasing. NAFLD can coexist with chronic viral hepatitis and exacerbate its progression. Oxidative stress has been recognized as a chronic liver disease progression-related and cancer-initiating stress response. However, there are still many unresolved issues concerning oxidative stress, such as the correlation between the natural history of the disease and promising treatment protocols. Recent findings indicate that oxidative stress is also an anti-cancer response that is necessary to kill cancer cells. Oxidative stress might therefore be a cancer-initiating response that should be down regulated in the pre-cancerous stage in patients with risk factors for cancer, while it is an anti-cancer cell response that should not be down regulated in the post-cancerous stage, especially in patients using anti-cancer agents. Antioxidant nutrients should be administered carefully according to the patients’ disease status. In this review, we will highlight these paradoxical effects of oxidative stress in chronic liver diseases, pre- and post-carcinogenesis.

Serum and plasma were found to be good materials for detecting cancer-specific DNA in the peripheral blood and the presence of KRAS mutations in blood-derived DNA may be used as a prognostic biomarker for patients with pancreatic cancer.