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S Arii

Publications and source records attributed to S Arii.

At least 37 records · Page 2Linked to original sources
PubMed2000

Protection by vascular endothelial growth factor against sinusoidal endothelial damage and apoptosis induced by cold preservation.

BACKGROUND: It is well known that sinusoidal endothelial cell (SEC) damage during cold preservation of liver tissue is closely involved in early graft failure. The objective of this study was to investigate the involvement of apoptosis in the SEC damage induced by cold preservation and to demonstrate the protective effect of vascular endothelial growth factor (VEGF) on SEC injury, including apoptotic changes. METHODS: Isolated SECs and liver tissue of Wistar rats were cold-preserved in University of Wisconsin (UW) solution, and the protective effect of VEGF was then investigated. Isolated SECs were cultured for 24 hr, and divided into the following 3 groups: Group A, in which the cells were cultured for an additional 27 hr, Group B, in which the cells were cold-preserved in UW solution for 3 hr, and then recultured for 24 hr, and Group C, in which 20 ng/ml of VEGF was added to both the culture medium and the UW solution of cells cultured according to the Group B protocol. Each group of SECs was morphologically examined using the phase contrast microscopic method and the transmission electron microscopic method (TEM), and quantitatively analyzed using the WST-1 assay. Rat livers were cold-preserved in UW solution and divided into the VEGF(+) group and the VEGF(-) group, depending on whether VEGF was added or not. Each group of livers were analyzed by scanning electron microscopic method (SEM) after 24 hr of preservation. The hyaluronic acid uptake rate (HUR) was also determined after 6 hr of preservation. After 24 hr of preservation and 6 hr of reperfusion, tissues were examined by TEM and by the terminal deoxynucleotidyl transferase d-uridine triphosphate nick end labeling (TUNEL) assay. RESULTS: The phase contrast microscopic method and the WST-1 assay showed a protective effect of VEGF against the injury to isolated SECs during cold preservation and subsequent reculturing. Apoptosis was detected immediately by TEM after isolation of SECs, and the number of apoptotic cells increased with the incubation time. This increase was accelerated after cold preservation. The scanning electron microscopic method and the hyaluronic acid uptake rate showed a protective effect of VEGF against SEC damage in the cold-preserved livers. In the liver tissue, the TEM and the TUNEL assay detected apoptosis of SECs only after cold preservation and subsequent reperfusion. VEGF suppressed the apoptosis of SECs induced by cold preservation in both isolated cells and liver tissue. CONCLUSIONS: We demonstrated that SEC damage in the cold preservation of liver tissue was caused mainly by apoptosis, which required subsequent reperfusion. Moreover, isolated SECs showed spontaneous occurrence of apoptotic changes during culture, and these changes were accelerated by the preceding cold preservation. This is the first report to demonstrate the apoptotic changes of SECs seen here were inhibited by VEGF.

Animals↗
PubMed2000

Physiological role of sinusoidal endothelial cells and Kupffer cells and their implication in the pathogenesis of liver injury.

We reviewed the morphological characteristics and physiological functions of hepatic sinusoidal endothelial cells (SECs) and Kupffer cells (KCs), both of which are major components of the hepatic sinusoid, and we showed the implication of these hepatic sinusoidal lining cells in the pathophysiology of the liver, based on our experimental studies. The most outstanding feature of SECs is that they are provided with numerous fenestrae, thereby allowing direct communication between the sinusoidal lumen and the space of Disse. Physiologically, SECs play a role in filtration function, endocytic function, and putative participation in the regulation of sinusoidal blood flow. As for KCs, they account for major portion of fixed macrophages in the entire body, and exhibit vigorous activity for phagocytosis, and produce many kinds of soluble mediators such as cytokines, prostanoids, oxygen radicals, and proteases. To determine whether these cells are implicated in pathophysiological processes in the liver we directed our attention to liver injury associated with sepsis and cold-preservation injury of liver tissue. In a septic rat model, we found that when KCs that included hepatic macrophages were activated, they released excess tissue-toxic mediators, probably leading to SEC damage. In the cold-preserved liver,we demonstrated that KCs were functionally activated and that the morphology of SECs was destroyed. When the liver was reperfused with plasma and a leucocyte suspension, hypercoagulability and increased leucocyte adherence occurred. In both experimental models, we demonstrated that KC blockade ameliorated the liver injury, and this was associated with the morphological improvement of SECs. Thus, we showed the pathogenetic implication of KCs and SECs, due possibly to microcirculatory disturbance in the hepatic sinusoid, and further emphasized the involvement of activated KCs in SEC impairment.

Animals↗
PubMed2000

Reduced stability of retinoblastoma protein by gankyrin, an oncogenic ankyrin-repeat protein overexpressed in hepatomas.

Hepatocellular carcinoma (HCC) is one of the most common cancers in Asia and Africa, where hepatitis virus infection and exposure to specific liver carcinogens are prevalent. Although inactivation of some tumor suppressor genes such as p53 and p16INK4Ahas been identified, no known oncogene is commonly activated in hepatocellular carcinomas. Here we have isolated genes overexpressed in hepatocellular carcinomas by cDNA subtractive hybridization, and identified an oncoprotein consisting of six ankyrin repeats (gankyrin). The expression of gankyrin was increased in all 34 hepatocellular carcinomas studied. Gankyrin induced anchorage-independent growth and tumorigenicity in NIH/3T3 cells. Gankyrin bound to the product of the retinoblastoma gene (RB1), increasing its phosphorylation and releasing the activity of the transcription factor E2F-1. Gankyrin accelerated the degradation of RB1 in vitro and in vivo, and was identical to or interacted with a subunit of the 26S proteasome. These results demonstrate the importance of ubiquitin-proteasome pathway in the regulation of cell growth and oncogenic transformation, and indicate that gankyrin overexpression contributes to hepatocarcinogenesis by destabilizing RB1.

3T3 Cells↗
PubMed2000

Soluble Flt-1 gene therapy for peritoneal metastases using HVJ-cationic liposomes.

Many studies have reported a close association between VEGF and tumor angiogenesis. The aim of the present study was to evaluate the effectiveness of gene therapy against cancer, including peritoneal metastasis, using a cDNA encoding a soluble type of Flt-1, one of the VEGF receptors. In a peritoneal metastasis model of MKN45 human gastric cancer cells, mice repetitively treated with intraperitoneal injections of HVJ-Fex, a type of HVJ-cationic liposome encapsulating a plasmid expressing soluble mFlt-1, exhibited smaller disseminated foci with fewer microvessels, thus resulting in a significantly longer survival period than the control mice. In another peritoneal metastasis model using HT1080S cells, a clone of HT1080 human fibrosarcoma cells stably transfected with hVEGF, treatments with HVJ-Fex also reduced the growth of disseminated foci without ascites formation. In conclusion, this study demonstrated that the peritoneal metastases of some cancers were largely dependent on VEGF, and that the repeated intraperitoneal transduction of a soluble flt-1 gene using HVJ-cationic liposomes suppressed peritoneal metastases, thereby contributing to a longer survival period.

Animals↗
PubMed2000

Results of surgical and nonsurgical treatment for small-sized hepatocellular carcinomas: a retrospective and nationwide survey in Japan. The Liver Cancer Study Group of Japan.

Hepatic resection (HX), percutaneous ethanol injection (PEI), and transcatheter arterial embolization (TCAE) have all been used in the treatment of patients with small-sized hepatocellular carcinomas (HCCs). However, the indications for these therapeutic modalities remain unclear. Therefore, the first step to minimize the debate on these indications is to review the standard results from each treatment based on an extensive survey. The participants in this study were patients with HCCs less than 5 cm in diameter who were enrolled in The Liver Cancer Study Group of Japan. The survival rates in the HX (n = 8,010), PEI (n = 4,037), and TCAE (n = 841) groups were calculated in relation to the number of tumors and the clinical stage. In the clinical stage I cases with a solitary tumor less than 2 cm in diameter and in all clinical stages with a solitary tumor greater than 2 cm and in the clinical stage II cases with 2 tumors greater than 2 cm, the HX group showed higher survival rates than the nonsurgical groups. The HX group had a higher male/female ratio and a younger mean age than the PEI or TCAE group. The ratio of HBs antigen-positive cases/hepatitis C virus antibody-positive cases in the PEI group was lower than that in the corresponding HX group. In contrast, the PIVKA-II values in the HX group tended to be higher than in the PEI group. In conclusion, these findings will provide useful information for selection of a therapeutic modality for small-sized HCCs.

Age Distribution↗
PubMed2000

Implications of human macrophage metalloelastase and vascular endothelial growth factor gene expression in angiogenesis of hepatocellular carcinoma.

OBJECTIVE: To determine molecular mechanisms involved in angiogenesis of hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA: Tumor angiogenesis is believed to derive from the balance between angiogenic stimulators and inhibitors. It has been suggested that the switch to the angiogenic phenotype requires both upregulation of the first and downregulation of the second. However, its molecular basis in vivo remains obscure. In this study the authors analyze the participation of two factors in angiogenesis of HCC- human macrophage metalloelastase (HME), a matrix metalloproteinase responsible for the generation of angiostatin, a potent angiogenesis inhibitor, and vascular endothelial growth factor (VEGF), the most potent endogenous angiogenic factor. METHODS: Tumorous and contiguous nontumorous tissues from 25 patients with HCC who underwent curative partial hepatectomy were subjected to Northern blot analysis to detect HME and VEGF messenger RNA (mRNA) expression. Western blot analysis was used to detected angiostatin. Tumor vascularity was evaluated using hepatic angiography. RESULTS: Eleven of the 15 cases expressing the HME gene showed hypovascular tumors, whereas hypervascular tumors were seen in 9 of the 10 HME-negative cases. The median of HME mRNA expression (tumorous/nontumorous ratio) was 6.5 (range 0-264.5) in the hypovascular group and 0 (range 0-3.2) in the hypervascular group. A stepwise logistic analysis revealed that HME and VEGF mRNA expression were two independent variables significantly affecting the vascularity of HCC tumors. CONCLUSION: HME gene expression is significantly associated with hypovascular tumors; moreover, angiogenesis in HCC is not determined by a single factor, but depends on the net balance between HME and VEGF gene expressions.

Adult↗
PubMed2000

Comparison of CT findings with resected specimens after chemoembolization with iodized oil for hepatocellular carcinoma.

OBJECTIVE: We assessed the role of dynamic CT in the evaluation of the efficacy of transarterial chemoembolization with iodized oil for hepatocellular carcinoma. MATERIALS AND METHODS: We examined 41 hepatocellular carcinoma lesions (mean diameter, 5.0 cm) in 40 patients (mean age, 60.6 years) who underwent transarterial injection of iodized oil alone (n = 3) or emulsion of iodized oil and doxorubicin hydrochloride (n = 10) followed by gelatin sponge particles (n = 27) and subsequent hepatectomy. On dynamic CT performed within 3 weeks before oily transarterial chemoembolization and within 4 weeks before surgery, we calculated the rate of necrosis on the basis of the assumption that the portion that retained iodized oil represented necrosis. We also calculated the reduction rate of the tumor. CT findings were compared with pathologic findings of resected specimens. RESULTS: Pathologic specimens and the necrosis rate measured on CT showed a good correlation (r = 0.83) when the portion of tumor that retained iodized oil was considered necrosis. No correlation existed if the portion that retained iodized oil was considered viable. We noted no significant correlation (r = 0.38) between the reduction rate of the tumor and necrosis rate. Also, we noted no correlation (r = 0.52) between the interval between transarterial oily chemoembolization and surgery and the reduction rate of the tumor. CONCLUSION: CT is suitable for the evaluation of the efficacy of oily chemoembolization for hepatocellular carcinoma on the basis of the assumption that the portion of tumor that retains iodized oil is necrotic. The rate of tumor size reduction measured on CT did not correlate with the therapeutic effect of chemoembolization.

Aged↗
PubMed2000

Enhancement of angiogenesis, tumor growth, and metastasis by transfection of vascular endothelial growth factor into LoVo human colon cancer cell line.

The expression of vascular endothelial growth factor (VEGF), a highly potent angiogenic molecule, is thought to be correlated with the development of colon cancer; however, direct evidence for a role of VEGF in metastasis is lacking. This study was designed to more directly establish the role of VEGF in the growth and metastasis of human colon cancer using a genetically engineered cancer cell line. A stable VEGF gene-transfected human colon cancer cell line, LoVo, was made by genetic manipulation using eukaryotic expression constructs designed to express the complete VEGF121 cDNA in the sense orientation. Transfected clones were screened for VEGF121 mRNA expression by Northern blot analysis and for VEGF121 protein expression by Western blot analysis. Consequently, we obtained S17 cells that expressed a high level of both VEGF mRNA and VEGF protein. A vector-transfected clone (V7 cell) was used as a control. The experiment with the dorsal air sac method revealed that S17 cells elicited a stronger directional out-growth of capillaries than V7 cells. S17 cells formed faster-growing tumors than did V7 cells when xenografted s.c. into nude mice, although there was no significant difference in their in vitro proliferation. Tumors derived from S17 cells had more vascularity, as assessed by counting capillary vessels after staining with factor VIII, than did tumors derived from V7 cells (P < 0.05). With regard to the metastatic potential, S17 cells exhibited a higher capacity for both hepatic metastasis after the splenic portal inoculation and peritoneal dissemination after i.p. injection than did V7 cells. However, S17 cells showed no apparent metastasis, despite their rapid growth after orthotopic implantation. In conclusion, the present study showed clearly that VEGF plays an important role in cancer growth due to stimulation of angiogenesis by accelerating cell growth after reaching the target organs.

Animals↗
PubMed2000

Mouse macrophage metalloelastase gene transfer into a murine melanoma suppresses primary tumor growth by halting angiogenesis.

Mouse macrophage metalloelastase (MME) has been associated with the generation of angiostatin, an internal fragment of plasminogen, which inhibits angiogenesis. To clarify whether tumor cells that consistently generate MME can suppress angiogenesis and, therefore, inhibit the growth of primary tumors in vivo, we transfected a cDNA coding for MME into murine B16-BL6 melanoma cells that grow rapidly and are MME deficient. The generation of active MME in MME-transfected clones was confirmed by immunoprecipitation followed by in vitro cleavage of plasminogen. Subcutaneous implantation of these stable clones in C57BL/6 mice inhibited primary tumor growth by an average of 73% (P = 0.00002), which directly correlated with a significant reduction of blood vessel formation (approximately 76%) in such tumors. Microangiography revealed massive angiogenesis in control tumors (mock and vector); however, in MME-transfected primary tumors it demonstrated a decreased and disrupted vascular network. Western blot analysis using a specific anti-mouse angiostatin antibody demonstrated a strong 38-kDa immunoreactive band in MME-transfected tumors and in the serum of mice bearing those tumor cells. These results show that placing MME gene directly into B16-BL6 melanoma cells is an effective approach to suppress primary tumor growth in vivo because it halts angiogenesis. Our data provide a feasible and promising strategy for gene therapy of cancer by targeting tumor vasculature.

Angiostatins↗
PubMed2000

[Hepatic arterial infusion chemotherapy for liver metastasis from esophageal squamous cell carcinoma].

Since 1993, we have treated 9 patients with liver metastases from esophageal squamous cell carcinoma using hepatic arterial infusion chemotherapy (HAI). These patients underwent esophagectomy and reconstruction with a stomach roll, and without preoperative chemotherapy and/or radiotherapy, HAI was effective in 5 patients (56%) with a CR in 2 patients. Preceding systemic chemotherapy was done with 7 patients, and was effective in 3 of them. HAI was also effective in all of them. In 3 patients with hepatic arterial anomalies, the right gastroepiploic artery and right gastric artery feeding the stomach roll could be preserved after changing the hepatic arterial flow. Two stomach roll ulcers and one hepatic arterial stenosis were experienced due to the toxicity of HAI. However, the nausea, vomiting, diarrhea, and/or myelosuppression seen with the preceding systemic chemotherapy were not experienced. In spite of the technical difficulties in catheterization and toxicities to stomach roll, HAI is considered to be more effective and feasible than systemic chemotherapy.

Aged↗
PubMed2000

[A complication with hepatic arterial infusion chemotherapy--a case of sepsis related to catheter tip dislocation to the duodenal bulb].

Extra-arterial dislocation of a catheter is one of the complications with hepatic arterial infusion chemotherapy. The authors report a case of sepsis related to catheter tip dislocation to the duodenal bulb. A 69-year-old man underwent sigmoidectomy for sigmoid colon cancer and partial hepatectomy for synchronous metastasis to the liver. We performed hepatic arterial catheterization via the femoral artery, and the patient underwent prophylactic hepatic arterial infusion chemotherapy with 5-FU. Thirty months later, computed tomography during arteriography (CTA) using a port system revealed the dislocation of catheter tip to the duodenal bulb. He showed no symptoms, so we kept him under observation. Sepsis occurred because of the dislocated catheter 39 months later. After removal of the catheter, the symptoms of sepsis disappeared.

Aged↗
PubMed1999

Production of specific antibody and T helper 1-dominant cytokine elicited by dendritic cells genetically modified with an adenovirus vector.

In this study we examined how dendritic cells (DCs) transduced with an adenovirus vector encoding a model tumor antigen (beta-galactosidase; beta-gal) would influence the humoral immune response to this antigen. Mice immunized with LacZ transduced DCs by an adenovirus vector could produce more anti-beta-gal antibody, especially of IgG2a subclass, than mice immunized with DCs alone, although the amount of serum IgG antibody did not increase. Compared with mice immunized with DCs alone, splenocytes of mice immunized with LacZ transduced DCs could produce more interferon-gamma (IFN-gamma) against the beta-gal derived, H-2Ld-restricted nonapeptide (TPHPARIGL) in a dose-dependent manner. These data suggest that DCs transduced with an adenovirus vector encoding the model tumor antigen could induce the T helper 1 (Th1) dominant response against the model tumor antigen.

Adenoviridae↗
PubMed1999

Morphologic alteration of hepatocytes and sinusoidal endothelial cells in rat fatty liver during cold preservation and the protective effect of hepatocyte growth factor.

BACKGROUND: Fatty liver grafts are considered to be one of the main factors of primary nonfunctioning graft in transplantation. We investigated here, the hepatic damage during cold preservation in a rat fatty liver model by ultrastructural observation, and examined the effect of human recombinant hepatocyte growth factor (hrHGF) on amelioration of the cold-preserved graft condition. METHODS: Wistar rats were fed a choline-deficient diet (CDD) for 7 days. Livers were stored in cold University of Wisconsin (UW) solution for 0, 4, and 24 hr. We evaluated the ultrastructural alteration of the hepatocytes, sinusoidal architecture, and endothelial cells (SECs) by scanning and transmission electron microscopy. Ex vivo, we measured alanine aminotransferase (ALT) in first effluent as an index of hepatocyte injury and the hyaluronic uptake rate (HUR) as that of SEC damage. We injected hrHGF into rats fed CDD for 7 days through the portal vein and also added it to the UW solution to determine whether or not the agent ameliorated the hepatic damage in cold-preserved fatty livers. RESULTS: In rats fed CDD for 7 days, the lesion occupied by fat deposits appeared to enlarge with the duration of cold preservation leading to the disarrangement of sinusoidal architecture. Furthermore, sinusoidal endothelial damage, in which gaps, blebs, microvilli, and sinusoid denudation were detected, appeared to be more severe in these livers than in the corresponding control livers. ALT significantly increased in the 4-hr cold-preserved livers of rats fed CDD for 7 days. HUR decreased with 4-hr cold preservation and/or with CDD feeding. Administration of hrHGF prevented the expansion of fatty droplets and reduced SEC injury as detected by morphological observations. Increase of ALT in first effluent was inhibited to about one fourth the level observed in the 4-hr cold-preserved livers of rats fed CDD. Moreover, HUR significantly increased with the pretreatment of hrHGF. CONCLUSION: The hepatic injury in both hepatocytes and SECs in cold-preserved fatty liver graft developed more rapidly and severely than in the corresponding controls and demonstrated a protective effect of hrHGF.

Animals↗
PubMed1999

Vascular endothelial growth factor-induced tumor angiogenesis and tumorigenicity in relation to metastasis in a HT1080 human fibrosarcoma cell model.

Although vascular endothelial growth factor (VEGF) is well known to be a potent mitogen for vascular endothelial cells, the role of VEGF in a developmental process of tumor angiogenesis and metastatic potential remains poorly understood. The present study was designed to investigate VEGF-induced vascular formation from a spatiotemporal viewpoint and to analyze VEGF-enhanced metastatic potential using stable clones of HT1080 human fibrosarcoma cells transfected with VEGF cDNA (S) or with vector alone (V). Microangiography revealed massive angiogenesis in the S cell-derived tumors and demonstrated that the angiogenesis occurred not in the tumor itself, but rather around the S cell tumor early after inoculation into the thigh muscles of mice. Thereafter, the angiogenesis extended in and around the tumor. The tumorigenicity of the S cells was higher than the V cells in the subcutaneous (s.c.) space, intraperitoneal space, liver and spleen. However, neither S cells nor V cells metastasized to the liver after an intrasplenic injection. Few apoptotic cells were detected in the S cell tumor, but many apoptotic cells were scattered in the V cell tumor. Our results indicate that VEGF facilitates tumorigenicity in various organs, possibly due to inducing angiogenesis in and around the tumor and preventing tumor cells from undergoing apoptosis, and suggest that VEGF may augment metastatic potential, by accelerating proliferative activity after reaching the target organ. Furthermore, VEGF-induced angiogenesis occurred preferentially around the tumor at an early period of tumor development, followed by neovascularization into the tumor.

Animals↗
PubMed1999

Implication of vascular endothelial growth factor in the development and metastasis of human cancers.

Vascular endothelial growth factor (VEGF) is a most potent angiogenic molecule. In this article, we demonstrated that VEGF is participated in the tumor angiogenesis of hepatocellular carcinoma, esophageal cancer, and pancreatic cancer. Furthermore, we revealed that VEGF is one of the molecules which are responsible for metastasis and prognosis in esophageal cancer and colon cancer. Although the mechanism on the induction of VEGF gene is still unclear in human cancer tissue, we obtained the informative evidence indicating that p53 mutation is involved in VEGF expression of esophageal cancer. Our experimental study with stable transfectant of VEGF gene provided the confirmative results showing that VEGF gene induces neovascularization in and around tumor and that VEGF augment metastastic potential by accelerating proliferative activity after reaching the target organ.

Cell Transformation, Neoplastic↗
PubMed1999

Pretreatment with soluble thrombomodulin prevents intrasinusoidal coagulation and liver dysfunction following extensive hepatectomy in cirrhotic rats.

The major cause of posthepatectomy liver dysfunction is supposed to be microcirculatory disturbance caused by imbalance of intrasinusoidal coagulation equilibrium. Thrombomodulin (TM) is a potent anticoagulant expressed on the endothelial cell surface that regulates the coagulation system by binding thrombin and accelerating the thrombin-catalyzed activation of protein C. Therefore, we examined the effect of soluble TM purified from human urine (UTM) on intrasinusoidal coagulation in cirrhotic rats. Dimethylnitrosamine-induced cirrhotic rats underwent 70% hepatectomy and received endotoxin 48 h after. UTM or vehicle alone was intravenously administered to each rat 30 min before endotoxin injection. UTM treatment attenuated the increases in cytosolic enzymes and serum hyaluronic acid level. The UTM supply improved the survival rate of the rats at 12 h after endotoxin challenge. Histologically, intrasinusoidal fibrin depositions and massive hepatocellular necrosis observed in control rats were scarcely found in UTM-treated rats. Immunohistochemical examination revealed that marked TM stains in sinusoidal endothelial cells were well preserved in UTM-treated rats. In conclusion, UTM administration prevented intrasinusoidal fibrin depositions and attenuated posthepatectomy liver dysfunction in cirrhotic rats.

Animals↗
PubMed1998

Expression of the Na+/Ca2+ exchanger emerges in hepatic stellate cells after activation in association with liver fibrosis.

Activation of hepatic stellate (Ito) cells is a final common pathway of liver fibrosis. The findings presented in this paper indicate that expression of Na+/Ca2+ exchanger (NCX) emerges in rat hepatic stellate cells after activation in vitro during primary culture or in vivo in response to intoxication with CCl4. NCX mRNA became detectable by Northern blot analysis in cultured stellate cells on day 3, as was alpha-smooth muscle actin, an indicator not only of smooth muscle differentiation but also of stellate cell activation. Western blot analysis showed expression of the exchanger protein in the activated stellate cells. Functional expression of the exchanger, monitored by Ni2+-sensitive, verapamil-insensitive intracellular free Ca2+ increases in response to reduction of extracellular Na+ concentration, became sizable by using Fura-2 in stellate cells by 7 days in culture. Furthermore, increased expression of the exchanger mRNA was found predominantly in stellate cells freshly isolated from the CCl4 model rat of hepatic fibrosis. Thus, it is concluded that NCX expression is closely associated with activation of hepatic stellate cells in vitro and in vivo. Because, even at the whole liver level, increased expression of NCX mRNA became observable after induction of liver fibrosis, it is suggested that NCX expression serves a useful diagnostic marker of liver fibrosis or cirrhosis.

Actins↗