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T Asahara

Publications and source records attributed to T Asahara.

At least 19 recordsLinked to original sources
PubMed2007

Rho-associated kinase inhibitor reduces tumor recurrence after liver transplantation in a rat hepatoma model.

Tumor recurrence after liver transplantation still remains a significant problem in patients with hepatocellular carcinoma. The small GTPase Rho/Rho-associated kinase (ROCK) pathway is involved in the motility and invasiveness of cancer cells. We investigated whether tacrolimus activated the Rho/ROCK signal pathway to promote the invasiveness of rat hepatocellular carcinoma cells. We also investigated whether the ROCK inhibitor Y-27632 suppressed tumor recurrence after experimental liver transplantation in a rat hepatocellular carcinoma model. Orthotopic liver transplantation was performed in hepatocellular carcinoma cell line McA-RH7777-bearing rats. Tacrolimus was administered to liver transplant rats and these rats were divided into two groups: the Y-27632-treated (10 mg/kg, for 28 days) group and the Y-27632-untreated group. Tacrolimus enhanced the cancer cell migration and stimulated phosphorylation of the myosin light chain (MLC), a downstream effector of Rho/ROCK signaling. Y-27632 suppressed the cancer cell migration and tacrolimus-induced MLC phosphorylation. Suppression of tumor recurrence after liver transplantation and significant prolongation of survival were observed in the Y-27632-treated rats in comparison with theY-27632-untreated rats. Tacrolimus stimulates the Rho/ROCK signal pathway to enhance the invasiveness of hepatocellular carcinoma, and the ROCK inhibitor Y-27632 can be used as a new antimetastatic agent for the prevention of tumor recurrence after liver transplantation.

Amides↗
PubMed2006

Near-infrared spectroscopic analysis of hemodynamics and mitochondrial redox in right lobe grafts in living-donor liver transplantation.

Near-infrared spectroscopy (NIRS), which enables non-destructive evaluation of hemoglobin (Hb) oxygenation and the redox state of cytochromeoxidase (Cyt.aa3) in living tissues, has been employed during surgery to detect possible impairment of hemodynamics and mitochondrial respiration in the anterior segment of a right lobe liver graft in living-donor liver transplantation (LDLT). Thirty-six patients undergoing LDLT using a right lobe graft without the middle hepatic vein (MHV) were enrolled in this study. During the course of harvesting and implantation, NIRS measurements were performed on the anterior segments of the liver grafts. In two recipients of liver grafts with Hb residue over 70% in the anterior segment after ex vivo flushing, the MHV tributary was reconstructed, while it was not reconstructed in the other 34 recipients. Of those 34 recipients, 16 recipients of liver graft with 40-70% Hb residue showed transient increase of transaminase levels after LDLT. Of those 16 recipients, six recipients who showed reduction in oxidized Cyt.aa3 in the anterior segment suffered from persistent hyperbilirubinemia after LDLT. In patients showing impairment of mitochondrial redox associated with congestion caused by deprivation of the MHV tributaries, reconstruction of the MHV tributaries might have a beneficial effect.

Adult↗
PubMed2005

Reciprocal role of vasculogenic factors and progenitor cells in atherogenesis.

While neovascularization plays an integral role in atherosclerosis, stimulation of angiogenesis does not appear to promote atherogenesis. This observation is important in view of recent advancements in angiogenic gene and cell therapy aimed at promoting new blood vessel growth in humans with vascular disease. Endothelial progenitor cells (EPCs) may actually prevent rather than provoke intimal thickening and vascular remodeling by promoting re-endothelialization in response to vascular trauma, as occurs with percutaneous transluminal vascular intervention for treating atherosclerotic vessels. Further support for the hypothesis that EPCs continuously repair vascular injury and contribute to the rejuvenation of vessels has been derived from animal studies demonstrating that serial injection of bone marrow-derived EPCs prevent atherogenesis, but that the quantity and quality of these cells deteriorate with aging. This chapter provides a summary of the influence of angiogenesis on atheromatous disease. Furthermore, the increasingly important relationship between atherosclerosis and newly emerging techniques in therapeutic angiogenesis (i.e., gene therapy and cell therapy with EPCs) is discussed.

Animals↗
PubMed2005

Stem cell biology for vascular regeneration.

The isolation of endothelial progenitor cells (EPCs) derived from bone marrow (BM) was one epoch-making event for the recognition of neovessel formation in adults occurring as physiological and pathological responses. The finding that EPCs home to sites of neovascularization and differentiate into endothelial cells (ECs) in situ is consistent with vasculogenesis, a critical paradigm that has been well described for embryonic neovascularization, but proposed recently in adults in which a reservoir of stem or progenitor cells contribute to vascular organogenesis. EPCs have also been considered as therapeutic agents to supply the potent origin of neovascularization under pathological conditions. This chapter highlights an update of EPC biology as well as its potential use for therapeutic regeneration.

Adult↗
PubMed2005

Calcineurin inhibitors block B-1 cell differentiation: the relevance to immunosuppressive treatment in ABO-incompatible transplantation.

Naturally occurring antibodies (Abs) against human blood group A/B-carbohydrate determinants are a major barrier to ABO-incompatible organ transplantation. We previously described that B cells recognizing the blood group A antigens (Ag) belong to a CD5+ B-1a cell subset that exists in blood group O human peripheral blood as well as in mice Recent evidence suggests that B-1a cells are selected by a T-independent type 2 (TI-2) Ag with repetitive arrays of epitopes which can promote BCR cross-linking. In support of the induced-differentiation model, CD5 can be induced on spleen B-2 cells in vitro after stimulation via surface IgM receptors, an induction that is blocked by cyclosporine (CsA). We examined whether mouse peritoneal cavity CD5+ B-1a cells could be reduced by CsA/tacrolimus. For 2 weeks, daily intraperitoneal (i.p.) injection of various doses of CsA/tacrolimus decreased the percentage of PerC CD5+ B-1a cells and increased B-2 cells in a dose-dependent fashion. However, this treatment had no impact on anti-A Abs, suggesting that Ab-producing cells may be resistant to calcineurin inhibitors. We speculate that specific elimination of the anti-A Ab-producing cells with subsequent CsA/tacrolimus therapy might induce lasting inhibition of anti-A Ab production in ABO-incompatible organ transplantation.

ABO Blood-Group System↗
PubMed2004

Quantitative measurement of hepatic portal perfusion by multidetector row CT with compensation for respiratory misregistration.

Our purpose was to determine whether hepatic portal perfusion assessed by multidetector row CT using compensation for respiratory misregistration can predict the severity of chronic liver disease. We carried out dynamic CT in 43 patients (chronic hepatitis: n=9; cirrhosis: n=24; normal liver: n=10). In this series, 20 patients had liver tumours. The CT protocol was designed to avoid respiratory artefacts and included two interscan breathing periods during the study. To compensate for respiratory misregistration, image sets in the same z-axis position were acquired from four-slice data on each scan, and the portal perfusion calculations were made according to the maximum slope method. Portal perfusion was compared with and without compensation for respiratory misregistration, and the different types of hepatic disease. In the liver tumour patients in particular, portal perfusion was compared with the degree of hepatic fibrosis in the liver sections. Portal perfusion in the patients without compensation for respiratory misregistration (1.10 ml min(-1)ml(-1)) was higher than that of those with compensation (0.99 ml min(-1)ml(-1); p=0.036). Hepatic portal perfusion of patients with chronic hepatitis (0.97 ml min(-1)ml(-1)) and liver cirrhosis (0.88 ml min(-1)ml(-1)) was less than that of patients with normal liver (1.32 ml min(-1)ml(-1); p=0.03, 0.001). Moderate correlation was seen between portal perfusion and the percentage of fibrosis in patients with liver tumours (r=0.55). Hepatic portal perfusion obtained by multidetector row dynamic CT using compensation for respiratory misregistration has the potential to improve non-invasive assessment of the degree of chronic liver disease.

Aged↗
PubMed2003

Autologous blood storage before hepatectomy for hepatocellular carcinoma with underlying liver disease.

BACKGROUND: Preoperative autologous blood donation has been suggested for patients with liver disease who are to undergo liver resection. The aim of this retrospective study was to clarify the risk factors for increased blood loss and the need for blood transfusion during hepatectomy for hepatocellular carcinoma (HCC). METHODS: From January 1996 to December 2000, 206 consecutive patients, 98.5 per cent of whom had underlying liver disease, underwent elective hepatectomy for HCC. RESULTS: Major hepatectomy was performed in 34 patients (16.5 per cent) and minor hepatectomy in 172 patients (83.5 per cent). The mean blood loss was 410 (median 260) ml. Eleven (5.3 per cent) of the 206 patients received blood transfusion during or after the operation. Operation time (P = 0.004) and central venous pressure (CVP) (P = 0.041) were independently correlated with blood loss of more than 1000 ml. Only preoperative haemoglobin level (P = 0.001) was independently correlated with the need for blood transfusion. CONCLUSION: In patients with underlying liver disease, maintaining CVP at a level below 5 cm H2O during parenchymal transection to reduce blood loss is more important than reserving autologous blood before the operation.

Adult↗
PubMed2003

Resection of hepatocellular carcinoma in a patient with congenital anomaly of the portal system.

Hepatic resection in a patient with an anomalous portal vein system is presented. A 53-year-old man was referred to our hospital for hepatic resection. Preoperative computed tomography (CT) and angiography demonstrated that the umbilical portion of the portal vein gave off major branches to the right anterior segment, and the hepatic tumor was located on the dorsal side of one of the right anterior portal branches near the umbilical portion. Partial hepatic resection was performed using the indocyanine green staining technique under operative echo guidance. Limited hepatic resection was indicated due to the patient's poor hepatic reserve function. His postoperative course was uneventful. This case emphasizes the importance of delineating the hepatic vascular anatomy before and during operation, especially in the case of an anomalous portal vein system.

Carcinoma, Hepatocellular↗
PubMed2003

[Local advanced lung cancer invaded thoracic vertebral bodies with unruptured cerebral aneurysm].

A 57-year-old man presented with the chief complaint of left shoulder pain in June 2001, and paridrosis of left upper trunk and left upper limb in July 2001. Head magnetic resonance imaging (MRI) showed 8 mm sized unrupture aneurysm of left middle cerebral artery, and chest computed tomography (CT) showed the lung tumor invaded thoracic vertebral bodies. The local advanced lung carcinoma (cT4N0M0) and unrupture aneurysm of left middle cerebral artery was diagnosed. The prevented clipping of unrupture aneurysm was performed at 11th September 2001, and left upper lobectomy, hemivertebrectomy and reconstruction of thoracic vertebral body (Th 3-5) with Modul' ICS at 12th October 2001. The pathological findings revealed squamous cell carcinoma. The staging was pT4N0M0, IIIB. The postoperative course was uneventful. After the radiotherapy (50 Gy), chemotherapy (gemcitabine and vinorelbine) was performed. But the radiation pneumonia was occurred and chemotherapy was intermitted. The steroid was administrated due to the radiation pneumonia, and the complication was improved. He discharged at 17th April 2002 and had no recurrence. The prevented clipping of unrupture cerebral aneurysm and the reconstruction of thoracic vertebral body (Th 3-5) with Modul' ICS were useful for the radical operation of the local advanced lung cancer.

Carcinoma, Squamous Cell↗
PubMed2003

Safety and growth suppressive effect of intra-hepatic arterial injection of AdCMV-p53 combined with CDDP to rat liver metastatic tumors.

Surgical resection is thought to be the best treatment for liver carcinoma, including hepatocellular carcinoma and metastatic liver carcinoma if there are a small number of tumors. Liver carcinoma is one of the main causes of death from cancer worldwide. The prognosis of liver carcinoma is still poor. Mutation of p53, which is well known as a tumor suppressor gene, is observed in many cases of advanced liver carcinoma. Cancer gene therapy using p53, which transduces the wild-type p53 gene in the tumor, is a promising new strategy for treating liver carcinoma. Selective and less invasive gene delivery to the liver tumor is necessary for clinical liver tumor gene therapy. The first purpose of the current study was to determine the best way to deliver the gene of interest to the liver tumor selectively. The second purpose was to study the tumor suppressive effect of intrahepatic arterial injection of an adenovirus vector with the p53 gene (AdCMV-p53), followed by administration of CDDP and noting its side effects. We injected AdCMV-LacZ via hepatic arteries of rats bearing RCN-9 colon cancer metastasis in the liver. Injection via the hepatic artery resulted in more successful gene transduction to the liver tumor in a tumor-selective manner than did injection via the portal vein. At 48 hrs after arterial injection of AdCMV-p53, CDDP (3 mg/kg) was administered in the peritoneal cavity of each rat. The use of CDDP with arterial injection of AdCMV-p53 resulted in more extensive apoptosis in the rat liver tumors without any deterioration in liver function. In conclusion, hepatic arterial injection of an adenovirus vector is better than portal vein injection for gene transduction efficiency, and causes no liver function disorder even when the injection is combined with CDDP.

Adenoviridae↗