Shinichiro Yamada

Outcome of hepatectomy in super-elderly patients with hepatocellular carcinoma.

Aim:  The aim of this study was to investigate the characteristics of super‐elderly hepatocellular carcinoma (HCC) patients aged 80 years or more who underwent hepatectomy and to clarify whether elderly patients with HCC benefit from hepatectomy.

Homing effect of adipose-derived stem cells to the injured liver: the shift of stromal cell-derived factor 1 expressions

Whether systemically transplanted human adipose‐derived stem cells (ADSCs) homed to the injured liver in nude mice under stress with subsequent hepatectomy (Hx) and ischemia‐reperfusion (I/R) was investigated in the present study. The types of cells in the liver that were involved in the homing of ADSCs were clarified, with focus on the stromal‐derived factor‐1 (SDF‐1)/C‐X‐C chemokine receptor type 4 (CXCR‐4) axis.

Specific miRNA expression profiles of non‐tumor liver tissue predict a risk for recurrence of hepatocellular carcinoma

It is reasonable to investigate non‐tumor liver tissues to predict a risk for development of hepatocellular carcinoma (HCC). A molecular analysis of chronically damaged liver tissues may identify specific miRNA expression profiles associated with a risk for multicentric (MC) HCC.

Prediction of recurrence of hepatocellular carcinoma after curative hepatectomy using preoperative Lens culinaris agglutinin‐reactive fraction of alpha‐fetoprotein

Aim:  Lens culinaris agglutinin A‐reactive fraction of α‐fetoprotein (AFP‐L3) status has been reported to be an independent prognostic factor in patients with hepatocellular carcinoma (HCC). In this study, we evaluated the clinical usefulness of measuring preoperative AFP‐L3 to predict the recurrence and prognosis of HCC after curative hepatectomy.

Dysfunction of liver regeneration in aged liver after partial hepatectomy.

A remarkable feature of the liver is its regenerative capacity following partial hepatectomy. However, the regenerative capacity of many organs and tissues loses its natural ability to divide with aging. In this study, we investigated the association of aging with endoplasmic reticulum stress, the cell cycle, autophagy, and apoptosis‐related genes during liver regeneration after hepatectomy.

Epigallocatechin gallate hinders human hepatoma and colon cancer sphere formation.

The long‐term survival of patients with hepatocellular carcinoma remains unsatisfactory because of the presence of cancer stem cells (CSCs), which are responsible for tumor recurrence and chemoresistance after hepatectomy. Drugs that selectively target CSCs thus offer great promise for cancer treatment. Although the antitumor effects of epigallocatechin gallate (EGCG) have been reported in some cancer cells, its effects on CSCs remain poorly studied. In this study, we investigated the effects of EGCG on human hepatoma and colon CSCs.

Senescence-related genes possibly responsible for poor liver regeneration after hepatectomy in elderly patients.

Liver regeneration likely decreases with age by an, as yet, incompletely understood mechanism, restricting the extent of hepatectomy. We therefore analyzed the effect of aging on liver regeneration and investigated mechanisms associate with poor regeneration of human liver.

Epithelial–mesenchymal transition-related genes are linked to aggressive local recurrence of hepatocellular carcinoma after radiofrequency ablation

We reported that poor prognoses of hepatocellular carcinoma (HCC) patients after radiofrequency ablation (RFA) are owing to up-regulation of expression of hypoxia-inducible factor-1 and epithelial cell adhesion molecule. We investigated aggressive progression in residual liver tumors (RLTs) after RFA to focus on expression of epithelial-mesenchymal transition (EMT)-related genes and miRNAs. Ten patients with recurrent HCC post-RFA who underwent hepatectomy (RFA group) and 78 patients with HCC without prior RFA (non-RFA group) were enrolled. We examined expression of transforming growth factor (TGF)-β, Twist, vimentin, and Snail-1 mRNAs in tumor tissues, and expression of miR-34a and miR-200c. Expression of TGF-β, Twist and Snail-1 in the RFA group was significantly higher than that in the non-RFA group (P < 0.05); vimentin expression in the RFA group was higher than that in the non-RFA group (P = 0.07). Expression of miR-200c and miR-34a in the RFA group was significantly lower than that in the non-RFA group (miR-200c: P = 0.04; miR-34a: P < 0.01). Increased expression of EMT markers through down-regulation of miRNA expression in RLTs after RFA may be related to poor prognoses of HCC patients with aggressive local recurrence after RFA.

The role of Fbxw7 expression in hepatocellular carcinoma and adjacent non‐tumor liver tissue

Fbxw7 is a tumor suppressor gene through ubiquitination and degradation of multiple oncoproteins. Loss of Fbxw7 expression is frequently observed in various human cancers. In the present study, we examined the role of Fbxw7 expression in both non‐tumor liver tissues and tumor tissues on clinicopathological significance.

Indoleamine 2,3-dioxygenase Affects the Aggressiveness of Intraductal Papillary Mucinous Neoplasms Through Foxp3(+)CD4(+)CD25(+) T Cells in Peripheral Blood

Objective Intraductal papillary mucinous neoplasms (IPMNs) have a high malignant potential. We previously reported that peripheral Foxp3+CD4+CD25+ T-cell (Foxp3+ Treg) populations significantly increase with IPMN pathological aggressiveness. Dendritic cell-mediated induction of active Tregs from naive CD4+ T cells requires indoleamine 2,3-dioxygenase (IDO). Here, we evaluated whether an IDO–Foxp3+ Treg interaction plays a role in IPMN pathological aggressiveness. Methods We evaluated peripheral blood samples and resected specimens from 12 patients with IPMN. We analyzed Foxp3+CD4+CD25+ T cells in peripheral blood by fluorescence-activated cell sorting, evaluated the resected specimens by anti-IDO antibody staining, and compared them with the patients’ clinicopathological factors. Results The pathological aggressiveness of IPMN was significantly associated with the number of peripheral Foxp3+ Tregs (P < 0.05) and IDO-positive cells per high-power field (HPF) (P < 0.01). There was a significant correlation between the numbers of peripheral Foxp3+ Tregs and IDO-positive cells/HPF (r = 0.625, P < 0.01). Patients with 7 or more IDO-positive cells/HPF had a significantly higher recurrence rate than those with less than 7 IDO-positive cells/HPF (P < 0.01, log-rank test). Conclusions Peripheral Foxp3+ Tregs accurately reflect the aggressiveness of IPMNs. An increase in Foxp3+ Tregs can be induced by local IDO-positive cells in IPMN.