LAT1 expression in IHCC

Background : Amino acid transporters, such as L-type amino acid transporter 1 (LAT1), have an effect on tumor growth, metastasis, and survival of various solid tumors. However, the role of LAT1 in patients with intrahepatic cholangiocarcinoma (IHCC) remains unknown. Methods : Forty-six patients who had undergone initial hepatic resection for IHCC at Tokushima University Hospital were enrolled in this study. Immunohistochemical analysis of LAT1 and phosphorylated Akt (p-AKT) was performed using resected specimens. Clinicopathological factors, including prognosis, were analyzed between LAT1-high and LAT1-low groups. Results : The LAT1-high group showed a higher proportion of periductal infiltrating type and higher carcinoembryonic antigen/carbohydrate antigen 19-9 levels compared with the LAT1-low group. Multivariate analysis revealed that LAT1-high expression was an independent prognostic factor for disease-free survival. Furthermore, the proportion of p-AKT positivity was higher in the LAT1-high group than in the LAT1-low group. Conclusions : LAT1 expression was associated with poor prognosis of IHCC and higher p-Akt expression

大腸癌肝転移におけるThrombospondin-1発現の役割とその分子メカニズム

Background/Purpose Thrombospondin-1 (THBS-1), a glycoprotein, is an endogenous inhibitor of angiogenesis and tumor growth. In this study, we investigated the clinical role and mechanism of THBS-1 expression in colorectal liver metastases, focusing on the relationships between its expression and tumor growth, epithelial–mesenchymal transition (EMT), and expression of other relevant molecules. Methods Ninety-four patients who initially underwent curative hepatic resection were enrolled in this study and correlations between expression of THBS-1 (THBS-1 high [n=35] and THBS-1 low [n=59]) and tumor growth, Ki-67 labelling index (Ki-67 LI), expression of other relevant molecules, and microvessel density (MVD) investigated. Results THBS1 low expression correlated with more advanced grade of liver and lymph node metastases and significantly worse overall survival than strong THBS1 expression (3-year survival: 96.7% vs. 65.4%, p<0.01). Multivariate analysis identified THBS1 low expression as an independent prognostic factor (HR=2.82, 95% CI=1.21–7.71, p=0.01). THBS-1 low expression correlated positively with high Ki-67 LI (p<0.05) and inversely with E-cadherin (p<0.05) and hypoxia inducible factor-1α (HIF-1α) expression (p<0.05); THBS-1 expression and MVD were not significantly correlated. Conclusions Low THBS-1 expression may be an independent poor prognostic factor that affects tumor growth and EMT acquisition. Additionally, THBS-1 may be regulated by the HIF-1 pathway

Complication of portal vein thrombosis after right hemihepatectomy in a patient lacking the portal vein bifurcation

Absence of portal vein bifurcation is a rare anomaly. We report a patient with this anomaly who underwent right hemihepatectomy for treatment of hepatocellular carcinoma. Although the procedure was carefully performed with a preoperative three-dimensional simulation and intraoperative cholangiography, postoperative portal vein thrombosis occurred

Impact of apparent diffusion coefficient on prognosis of early hepatocellular carcinoma: a case control study

Abstract Background We investigated the usefulness of apparent diffusion coefficients (ADC) from diffusion-weighted images (DWI) obtained using magnetic resonance imaging (MRI) for prognosis of early hepatocellular carcinoma (HCC): Barcelona Clinic Liver Cancer (BCLC) stage 0 and A. Methods We enrolled 102 patients who had undergone surgical resection for early HCC: BCLC stage 0 and A, and calculated their minimum ADC using DWI-MRI. We divided patients into ADCHigh (n = 72) and ADCLow (n = 30) groups, and compared clinicopathological factors between the two groups. Results The ADCLow group showed higher protein induced by vitamin K absence-II (PIVKA-II) levels (p = 0.02) compared with the ADCHigh group. In overall survival, the ADCLow group showed significantly worse prognosis than the ADCHigh group (p < 0.01). Univariate analysis identified multiple tumors, infiltrative growth, high PIVKA-II, and low ADC value as prognostic factors. Multivariate analysis identified infiltrative growth and low ADC value as an independent prognostic factor. Conclusion ADC values can be used to estimate the prognosis of early HCC

Curcumin-Mediated Resistance to Lenvatinib via EGFR Signaling Pathway in Hepatocellular Carcinoma

Lenvatinib is a multi-kinase inhibitor approved as a first-line treatment for patients with unresectable advanced hepatocellular carcinoma (HCC). However, its response rate is unsatisfactory, primarily due to the acquisition of resistance, which limits its clinical significance for treating patients with HCC. Recent evidence suggests that epidermal growth factor receptor (EGFR) activation can trigger Lenvatinib-resistance; and is considered an important therapeutic target in HCC. Curcumin, one of the most studied naturally occurring botanicals with robust anti-cancer activity, is also reported to be a potent tyrosine kinase inhibitor. In this study, we hypothesized that the anti-EGFR potential of Curcumin might help overcome Lenvatinib resistance in HCC. We established two Lenvatinib-resistant cells and discovered that a combination of Curcumin and Lenvatinib exhibited a synergistic anti-tumor efficacy in the resistant HCC cell lines. In line with previous reports, Lenvatinib-resistant cell lines revealed significant activation of the EGFR, and genomewide transcriptomic profiling analysis identified that the PI3K-AKT pathway was associated with Lenvatinib resistance. The combination treatment with Curcumin and Lenvatinib dramatically suppressed gene and protein expression of the EGFR-PI3K-AKT pathway, suggesting Curcumin overcomes Lenvatinib resistance via inhibition of EGFR. We further validated these findings in tumor spheroids derived from resistant cell lines. In conclusion, we, for the first time, report that Curcumin reverses Lenvatinib resistance in HCC, and that their combination has clinical application potential for adjunctive treatment in HCC