BACKGROUND/AIMS: p53 mutations have been reported to be a poor prognostic indicator in patients with HCC treated by surgical resection because of the association with frequent recurrence and shorter survival periods. Although poor differentiation of tumor has been considered to be associated with p53 mutation more frequently, the exact causes of unfavorable prognosis have not been clarified. METHODS: To evaluate the relationship of p53 mutation and details of histological features, we examined 20 HCCs and surrounding liver tissues from the patients treated with surgical resection using direct sequencing of p53 gene at exons 5, 6, 7 and 8, and analyzed histopathologic features. We also analyzed the clinical, biochemical and radiological characteristics including the recurrences of tumor and survival periods in HCC patients with p53 mutant comparing to those with wild type p53 gene. RESULTS: p53 mutants were found in 9 (45%) out of 20 resected HCC tissues, none from any surrounding tissues. p53 mutations were all point substitutions of a base; 5 in exon 8, 4 in exon 5 and 1 in exon 7. Between patients with mutants and those with wild type of p53 gene, there were no differences in age, sex, serum ALT, albumin, bilirubin and AFP levels, and HBV-ositivity. HCCs with p53 mutants tended to be larger in size (14% in < 5 cm vs 67 % in > 5 cm; p=0.03) and multinodular in type (3/9 vs 0/11; p=0.07). p53 mutants tended to be found in poorly differentiated HCCs comparing to wild types. Even though there was no evidence of vascular or biliary invasion radiologically in all, 5 of 9 p53 mutant (+) (56%) and none of 11 p53-utant (- cases showed vascular invasions microscopically (p<0.01). However, there was no correlation between p53 mutations in tumor tissues and formation of capsules, biliary invasions or association with cirrhosis. During follow-p periods (median: 22;2 -8 mos) recurrences of HCC had been found in 6 of 9 patients with mutants (67%) in contrast to only 2 of 11 with wild types (18%)(p=0.07). Extrahepatic metastases were also common in patients with p53 mutant than those without it (56% vs 9%; p=0.05). Consequently, the 1 year cancer free survival rate of HCC patients with p53 mutant was significantly lower than that with wild type (44% vs 82%; p=0.02). CONCLUSIONS: Thus, it is suggested that p53 mutations tend to be commonly associated with microvascular invasions as well as poor differentiation microscopically, which may result in micrometastasis and frequent recurrences, and consequently shorter survival periods in HCC patents undergoing surgical resection.
Bilirubin ; Capsules ; Carcinoma, Hepatocellular* ; Exons ; Fibrosis ; Genes, p53 ; Humans ; Liver ; Neoplasm Metastasis ; Neoplasm Micrometastasis ; Prognosis* ; Recurrence ; Survival Rate

Background: Tea tree oil has antiviral, antimicrobial and antifungal effects and Mastic oil has antifungal and anticancer effects. For synergistic effects of oils, blending oil containing a mixture of two to three oils is recommended. This study aimed to determine the antibacterial effects of Tea tree oil, Mastic oil, and Blending oil containing the two oils in a mixture, to verify and suggest the potential use of these oils as a substance to prevent dental caries. Methods: Tea tree oil, Mastic oil, and Blending oil with a 1:1 blend of the two oils were diluted in liquid medium to 0% (negative control), 0.5%, 1.0%, and 2.0%. Streptococcus mutans was applied to each experimental group of the three diluted oils and after 8 h culture, the optical density (OD) was measured and the growth inhibition rate for S. mutans was estimated. Results: Tea tree oil had significantly low OD values across all concentrations (p<0.05) without significant variation among different concentrations (p>0.05). Mastic oil did not significantly vary in OD compared to the negative control across all concentrations (p>0.05) without significant variation among different concentrations (p>0.05). Blending oil, compared to the negative control, did not significantly vary in OD at 0.5% (p>0.05) but significant variation was found as the concentration increased (p<0.05). Additionally, for Tea tree oil and Mastic oil, the growth inhibition rate showed no significant variation according to concentration (p>0.05), whereas for Blending oil, the growth inhibition rate for S. mutans showed a significant difference at 1.0% (p<0.05) and at higher concentrations. Conclusion Blending oil containing a Tea tree oil and Mastic oil demonstrated a significant growth inhibition effect on S. mutans from the concentration of 1.0%, which suggested its potential use as an effective antibacterial agent for dental caries.

Background: Enavogliflozin is a novel sodium-glucose cotransporter-2 inhibitor currently under clinical development. This study evaluated the efficacy and safety of enavogliflozin as an add-on to metformin in Korean patients with type 2 diabetes mellitus (T2DM) against dapagliflozin. Methods: In this multicenter, double-blind, randomized, phase 3 study, 200 patients were randomized to receive enavogliflozin 0.3 mg/day (n=101) or dapagliflozin 10 mg/day (n=99) in addition to ongoing metformin therapy for 24 weeks. The primary objective of the study was to prove the non-inferiority of enavogliflozin to dapagliflozin in glycosylated hemoglobin (HbA1c) change at week 24 (non-inferiority margin of 0.35%) (Clinical trial registration number: NCT04634500). Results: Adjusted mean change of HbA1c at week 24 was –0.80% with enavogliflozin and –0.75% with dapagliflozin (difference, –0.04%; 95% confidence interval, –0.21% to 0.12%). Percentages of patients achieving HbA1c <7.0% were 61% and 62%, respectively. Adjusted mean change of fasting plasma glucose at week 24 was –32.53 and –29.14 mg/dL. An increase in urine glucose-creatinine ratio (60.48 vs. 44.94, P<0.0001) and decrease in homeostasis model assessment of insulin resistance (–1.85 vs. –1.31, P=0.0041) were significantly greater with enavogliflozin than dapagliflozin at week 24. Beneficial effects of enavogliflozin on body weight (–3.77 kg vs. –3.58 kg) and blood pressure (systolic/diastolic, –5.93/–5.41 mm Hg vs. –6.57/–4.26 mm Hg) were comparable with those of dapagliflozin, and both drugs were safe and well-tolerated. Conclusion Enavogliflozin added to metformin significantly improved glycemic control in patients with T2DM and was non-inferior to dapagliflozin 10 mg, suggesting enavogliflozin as a viable treatment option for patients with inadequate glycemic control on metformin alone.