Anti-Donor Regulatory T-Cell Therapy in Adult-to-Adult Living Donor Liver Transplantation: A Case Report.

We report on the case of a 50-year-old female patient with symptomatic polycystic liver disease who underwent living donor liver transplantation (LDLT) using right liver graft from her ABO-identical husband. To achieve operational tolerance, regulatory T-cell (T-reg)-based cell therapy was applied, following the protocol introduced by Todo et al. Briefly, donor lymphocytes were collected by leukapheresis 20 days before LDLT without any adverse events, and the cells were irradiated with a dose of 30 Gy and kept frozen.

Triazolopyrimidine derivative NK026680 and donor-specific transfusion induces CD4CD25Foxp3 T cells and ameliorates allograft rejection in an antigen-specific manner.

We have previously demonstrated the unique properties of a new triazolopyrimidine derivative, NK026680, which exerts immunosuppressive effects in rat heart transplant model and confers tolerogeneic properties on ex vivo-conditioned dendritic cells in mice. We herein demonstrate that NK026680 promotes the expansion of regulatory T cells (Tregs) with potent immunoregulatory effects when used in combination with donor-specific transfusion (DST). BALB/c (H-2) heart graft were transplanted into C57BL/6 (H-2) mice following intravenous injection of donor splenocytes (DST) and oral administration of NK026680.

Expanded living-donor liver transplantation criteria for patients with hepatocellular carcinoma based on the Japanese nationwide survey: the 5-5-500 rule - a retrospective study.

Expansion of the liver transplantation indication criteria for patients with hepatocellular carcinoma (HCC) has long been debated. Here we propose new, expanded living-donor liver transplantation (LDLT) criteria for HCC patients based on a retrospective data analysis of the Japanese nationwide survey. A total of 965 HCC patients undergoing LDLT were included, 301 (31%) of whom were beyond the Milan criteria.

Anti-donor regulatory T cell therapy in liver transplantation.

Liver transplantation is accepted as the most reliable therapeutic option for patients with end-stage liver failure, but lifelong administration of immunosuppressive agents continues to be problematic due to various drug-induced morbidities and the risk of mortality. Complete cessation of immunosuppressive drugs while maintaining normal graft function and histology, called operational tolerance, has the potential to overcome these long-standing problems. Previously, we reported the results of a pilot study of anti- donor regulatory T cell therapy in 10 consecutive adult patients who underwent living donor liver transplantation (LDLT), of whom 7 patients successfully stopped immunosuppression for nearly 2 years.

Clinical impacts of mesothelin expression in gastrointestinal carcinomas.

Mesothelin, C-ERC/mesothelin is a 40-kDa cell surface glycoprotein that is normally present on normal mesothelial cells lining the pleura, peritoneum, and pericardium. Moreover, mesothelin has been shown to be overexpressed in several human cancers, including virtually all mesothelioma and pancreatic cancer, approximately 70% of ovarian cancer and extra bile duct cancer, and 50% of lung adenocarcinomas and gastric cancer. The full-length human mesothelin gene encodes the primary product, a 71-kDa precursor protein.

Hydrogen Gas Ameliorates Hepatic Reperfusion Injury After Prolonged Cold Preservation in Isolated Perfused Rat Liver.

Hydrogen gas reduces ischemia and reperfusion injury (IRI) in the liver and other organs. However, the precise mechanism remains elusive. We investigated whether hydrogen gas ameliorated hepatic I/R injury after cold preservation.

Olfactory Receptor Family 7 Subfamily C Member 1 Is a Novel Marker of Colon Cancer-Initiating Cells and Is a Potent Target of Immunotherapy.

Purpose: Cancer-initiating cells (CICs) are thought to be essential for tumor maintenance, recurrence, and distant metastasis, and they are therefore reasonable targets for cancer therapy. Cancer immunotherapy is a novel approach to target cancer. In this study, we aimed to establish novel CIC-targeting immunotherapy.

A pilot study of operational tolerance with a regulatory T-cell-based cell therapy in living donor liver transplantation.

Unlabelled: Potent immunosuppressive drugs have significantly improved early patient survival after liver transplantation (LT). However, long-term results remain unsatisfactory because of adverse events that are largely associated with lifelong immunosuppression. To solve this problem, different strategies have been undertaken to induce operational tolerance, for example, maintenance of normal graft function and histology without immunosuppressive therapy, but have achieved limited success.

Novel anti-inflammatory agent 3-[(dodecylthiocarbonyl)-methyl]-glutarimide ameliorates murine models of inflammatory bowel disease.

Objective And Design: To examine the effect of 3-[(dodecylthiocarbonyl)-methyl]-glutarimide (DTCM-G), a novel anti-inflammatory agent that inhibits lipopolysaccharide (LPS) activation of RAW264.7 macrophages, on murine models of colitis and RAW264.7 cells.

Resection of liver metastasis derived from alpha-fetoprotein-producing gastric cancer-report of 4 cases.

As is the case for metastatic liver tumors derived from standard gastric cancers, there is no consensus about the optimal treatment for metastatic liver tumors derived from alpha-fetoprotein (AFP)-producing gastric cancer, including regarding the surgical indications for such lesions. We report the cases of 4 patients in whom metastatic liver tumors derived from AFP-producing gastric cancer that were curatively resected. One of the patients had a thrombus in his inferior vena cava at the time of the liver resection, and both the liver tumor and thrombus were completely removed.

Importance of luminal membrane mesothelin expression in intraductal papillary mucinous neoplasms.

The present study demonstrated that luminal membrane mesothelin expression is a reliable prognostic factor in gastric cancer. Intraductal papillary mucinous neoplasms (IPMNs) often exhibit a spectrum of dysplasia, ranging between adenoma and carcinoma. Therefore, an immunohistochemical analysis of mesothelin expression in IPMN was performed in the present study, focusing on the localization of mesothelin.

3-[(dodecylthiocarbonyl)methyl]-glutarimide attenuates graft arterial disease by suppressing alloimmune responses and vascular smooth muscle cell proliferation.

Background: Graft arterial disease (GAD) is a major cause of late graft loss after organ transplantation. Alloimmune responses and vascular remodeling eventually cause the transplant organ to develop GAD. In this study, we aimed to limit the development of GAD by inhibiting alloimmune responses and vascular smooth muscle cell (VSMC) proliferation with a new compound, 3-[(dodecylthiocarbonyl)methyl]-glutarimide ([DTCM]-glutarimide), in a murine cardiac model of GAD.

Multiplication of alpha-fetoprotein and protein induced by vitamin K absence-II is a powerful predictor of prognosis and recurrence in hepatocellular carcinoma patients after a hepatectomy.

Aim: To evaluate the oncological implications of multiplication of α-fetoprotein (AFP) and protein induced by vitamin K absence or antagonists-II (PIVKA-II) in patients with hepatocellular carcinoma (HCC).

Methods: Data were prospectively collected from 516 consecutive patients who underwent a curative primary hepatectomy for HCC between 1998 and 2010. The AP-factor (AFP × PIVKA-II) was evaluated in relation to 2-year survival outcomes by receiver-operator curve analysis to determine the cut-off values.

Hydrogen sulfide augments survival signals in warm ischemia and reperfusion of the mouse liver.

Background And Purpose: Hydrogen sulfide (H2S) ameliorates hepatic ischemia and reperfusion injury (IRI), but the precise mechanism remains elusive. We investigated whether sodium hydrogen sulfide (NaHS), a soluble derivative of H2S, would ameliorate hepatic IRI, and if so, via what mechanism.

Methods: Mice were subjected to partial warm ischemia for 75 min followed by reperfusion.

Chondroma of the diaphragm mimicking a giant liver tumor with calcification: report of a case.

Extraskeletal chondroma is an unusual benign tumor, which rarely arises in the diaphragm. We report a case of chondroma of the diaphragm in a 31-year-old woman. Initially, a benign liver tumor with calcification was suspected, based on pre and intraoperative examination findings.

Long-term outcome of laparoscopic hepatectomy in patients with hepatocellular carcinoma.

Background/aims: The long-term prognosis for patients with hepatocellular carcinoma (HCC) who undergo laparoscopic hepatectomy has not been well compared with that for patients after open hepatectomy.

Methodology: We analyzed patient survival (PS) and disease-free survival (DFS) of 310 consecutive patients who underwent primary hepatectomy between January 2001 and March 2010. The patients were divided into Group LAP (laparoscopic approach) (n = 24) and Group OPN (with open laparotomy) (n = 286).

Small-for-size syndrome in living-donor liver transplantation using a left lobe graft.

In living-donor liver transplantation with a left lobe graft, which can reduce the burden on the donor compared to right lobe graft, the main problem is small-for-size (SFS) syndrome. SFS syndrome is a multifactorial disease that includes aspects related to the graft size, graft quality, recipient factors and even technical issues. The main pathophysiology of SFS syndrome is the sinusoidal microcirculatory disturbance induced by shear stress, which is caused by excessive portal inflow into the smaller graft.

Surgical management of hepatocellular carcinoma with tumor thrombi in the inferior vena cava or right atrium.

Background: The prognosis for advanced hepatocellular carcinoma (HCC) with tumor thrombi in the inferior vena cava (IVC) or right atrium (RA) is poor, and there is no established effective treatment for this condition. Thus study aimed to evaluate the efficacy of surgical resection and prognosis after surgery for such cases.

Methods: Between January 1990 and December 2012, 891 patients underwent hepatectomy for HCC at our institution.

Efficacy of DHMEQ, a NF-κB inhibitor, in islet transplantation: I. HMGB1 suppression by DHMEQ prevents early islet graft damage.

Background: Pancreatic islet transplantation (PITx) is an attractive treatment option for restoring appropriate glucose homeostasis in type 1 diabetes patients. Although islet grafts can successfully engraft after PITx, large numbers of islet grafts are required mainly because immune reactions, including inflammation, destroy islet grafts. In these processes, nuclear factor (NF)-κB plays a central role.

Efficacy of DHMEQ, a NF-κB inhibitor, in islet transplantation: II. Induction DHMEQ treatment ameliorates subsequent alloimmune responses and permits long-term islet allograft acceptance.

Background: Long-term graft deterioration remains a major obstacle in the success of pancreatic islet transplantation (PITx). Antigen-independent inflammatory and innate immune responses strengthen subsequent antigen-dependent immunity; further, activation of nuclear factor (NF)-κB plays a key role during these responses. In this study, we tested our hypothesis that, by the inhibition of NF-κB activation, the suppression of these early responses after PITx could facilitate graft acceptance.