PubMed Health⌕ Search

Biomedical subjects

S Arii

Publications and source records attributed to S Arii.

At least 19 recordsLinked to original sources
PubMed2005

Comparison of the vector systems for gene transduction into rat dendritic cells and peritoneal exudate cells.

Specialized antigen-presenting cells (APC), known as dendritic cells (DC), play a pivotal role in initiating primary immune responses. It has been reported that several vector systems, including adenoviral vectors, retroviral vectors, Hemagglutinating Virus of Japan (HVJ)-related vectors, and electroporation, are able to transduce genes into mouse and human DC. This has not been achieved for rat DC. To our knowledge, there is no direct evidence to support the view that the currently used vector systems are able to transduce genes into mature DC. Because most, if not all, gene transfer studies investigating DC or DC-related cell populations are carried out using heterogeneous groups of cells, it is therefore very important to determine to what extent gene transduction occurs in rat DC, and also selected mature DC (CD161a+ fully mature DC). In this study, we provide evidence that none of 4 vector systems are able to transfer genes into fully mature rat DC, which are derived from bone marrow cells (BMC), driven by Flt3/Flk2 ligand and interleukin (IL)-6, and purified by CD161a. Nevertheless, the most efficient gene transduction was observed in the developing DC progenitor cells during the long-term culture of rat BMC, and its gene expression was successfully achieved after 2 weeks of culture only with a human immunodeficiency virus (HIV)-based lentiviral vector system. The most critical time point for lentiviral gene transduction was around the 7th day from the beginning of culture with lentiviral vectors. Rat peritoneal exudate cells (PEC) and another cell line (K562) were easily transducted by adenoviral vectors and lentiviral vectors.

Adenoviridae↗
PubMed2005

Immunosuppressive effect of long-term drainage of thoracic duct on immunological memory in adult thymectomized rats.

Profound reduction of the recirculating lymphocyte pool using thoracic duct drainage (TDD), a method developed by Gowans et al, has been shown to be of limited immunosuppressive value when applied in experimental as well as in clinical settings across major histocompatibility antigen complex (MHC) differences. This limitation is due to the observation that animals, in particular mice, are normally not able to have the drainage last longer than 8 to 10 days. However, using a simple modification of TDD, we have established a long-term TDD method, ie, more than 20 days. Combining this long-term TDD with adult thymectomy, we have examined the life span of naive and memory T cells specific for the minor histocompatibility antigen H-Y in female lewis rats. Furthermore, we demonstrated that memory T cells specific for the H-Y antigen do not appear to be recirculating lymphocytes.

Animals↗
PubMed2004

Treatment strategy for Boerhaave's syndrome.

Esophageal rupture is a potentially mortal condition. Rapid and correct diagnosis, and urgent surgical treatment with esophagectomy is indicated, but conservative and other surgical treatments have also been reported recently. The treatment strategies for esophageal rupture are discussed here, based on our experiences with four cases during the last 10 years. They were admitted urgently and each was treated by a different method. Three of them underwent emergency operations, one undergoing primary closure of the ruptured esophagus, another received a T-tube insertion from the ruptured site with omental flap, and the third an esophagogastrectomy. The fourth case was treated conservatively. All patients survived and were discharged 36-144 days post treatment. One of them was readmitted for debridement of necrotic rib. In conclusion, the prompt and accurate diagnosis of esophageal rupture is crucial for a subsequent successful treatment. Conservative treatment or operation including esophagectomy will be determined by the severity of the condition.

Adult↗
PubMed2002

Hand-assisted laparoscopic hepatic resection.

Thanks to recent advances, performance of liver resection is now possible using laparoscopic procedures. However, still there are some difficulties to overcome. The hand-assisted method lends safety and reliability to the laparoscopic procedure. A 54-year-old man diagnosed with hepatocellular carcinoma (HCC) was referred for hepatectomy. Angiography with computed tomography (CT) scans revealed a 2-cm hepatocellular carcinoma (HCC) at segment V, close to the gallbladder. A hand-assisted laparoscopic hepatic resection was performed. Four 10-mm trocars, one for wall lifting and three for working, were placed in the upper abdomen. A small incision was added at the right side of umbilicus, and the operator's left hand was inserted through it. A microwave tissue coagulator and laparoscopic ultrasonic dissector were used for liver resection. Total operation time was 162 min; blood loss was 20 g. The postoperative course was uneventful, and the postoperative hospital stay was 7 days. We thus demonstrated that laparoscopic liver resection is safer and easier when the hand of the operator can be inserted into the abdomen. The small incision does not greatly diminish the benefits that accrue from minimally invasive laparoscopic surgery. The hand-assisted procedure allows better access to the tumor. In addition, hand assistance restores the sense of touch to the operator and is an effective means of controlling sudden and unexpected bleeding.

Angiography↗
PubMed2001

Laparoscopic enucleation of an insulinoma of the pancreas tail.

A 29 year-old woman with a tumor of the pancreatic tail was referred to our institute. The tumor was confirmed to be a solitary benign insulinoma that protruded from the pancreas and was distant from the main pancreatic duct. A laparoscopic enucleation was performed with Laparoscopic Coagulating Shears (LCS). The postoperative course was uneventful. The laparoscopic enucleation for benign pancreatic tumor was thought to be a feasible procedure when the appropriate instruments were used.

Adult↗
PubMed2001

sFlt-1 gene-transfected fibroblasts: a wound-specific gene therapy inhibits local cancer recurrence.

Local recurrence occurs frequently at the site of injury after surgical resection. On the other hand, fibroblasts have been shown to accumulate in the injured area to heal and remodel the damaged tissues. Therefore, fibroblasts are likely to be useful as wound-specific vectors for delivery of genes to sites of surgically injury. The present study was performed to investigate wound-specific migration of exogenously administered fibroblasts and efficacy of gene therapy using genetically engineered fibroblasts in an i.p. wound recurrence model in rats. We demonstrated that fibroblasts transfected with the GFP gene accumulated specifically around the site of injury immediately after i.p. injection. Then, fibroblasts transfected with an adenovirus designated as AdFex that encoded the soluble form of Flt-1 (sFlt-1), a vascular endothelial growth factor receptor, were administered i.p. to the rats to examine inhibition of tumor growth. At day 16 after implantation, a significantly smaller tumor volume and less microvessel density in wound sites were observed in the AdFex/fibroblast-treated rats than in controls. Furthermore, this treatment also resulted in an improved survival rate. In conclusion, autologous fibroblasts show promise as a wound-specific vector for gene therapy, and administration of sFlt-1 gene-engineered fibroblasts contributed to local control of the tumor around the injured tissue.

Animals↗
PubMed2001

Mouse macrophage metalloelastase gene delivery by HVJ-cationic liposomes in experimental antiangiogenic gene therapy for murine CT-26 colon cancer.

We previously demonstrated that gene replacement of mouse macrophage metalloelastase (MME) into murine melanoma cells that grow rapidly and are MME deficient suppresses the primary tumor growth in vivo by halting angiogenesis. The aim of the present study was to evaluate the effectiveness of gene therapy against cancer using a cDNA-encoding MME gene. In a subcutaneous tumor model of CT-26 mouse colon cancer cells that are MME deficient, syngeneic mice repetitively treated with direct injections into the tumors of MME- hemagglutinating virus of Japan (HVJ), a type of HVJ-cationic liposome encapsulating a plasmid expressing MME, developed smaller tumors (210 +/- 47.2 mm(3) versus 925 +/- 156 mm(3) mean +/- SEM; p = 0.0004) with fewer microvessels (10.25 +/- 1.03 vs. 17.25 +/- 2.14; p = 0.03) than control mice. TUNEL staining revealed a significant increase of apoptotic cells in the MME-HVJ liposomes-treated tumors compared with control tumors. MME was effectively expressed in the s.c. tumors treated with MME-HVJ liposomes, inducing angiostatin generation in those tumors, as demonstrated by Western blot analysis. In conclusion, our study demonstrated that repeated in vivo transduction of the MME gene directly into the tumors using HVJ-cationic liposomes suppressed the tumor growth by an antiangiogenic mechanism, providing, then, a feasible strategy for gene therapy of cancer.

Angiostatins↗
PubMed2001

Human macrophage metalloelastase gene expression in colorectal carcinoma and its clinicopathologic significance.

BACKGROUND: Human macrophage metalloelastase (HME), also referred as matrix metalloproteinase 12, has been shown to convert plasminogen into angiostatin, an essential inhibitor of tumor angiogenesis. The current study was designed to investigate the association of HME mRNA expression with disease progression of in patients with colorectal carcinoma. METHODS: The expression of HME mRNA was quantified by Northern blot analysis in tumorous (T) and nontumorous (N) tissues obtained from 54 patients with primary colorectal carcinoma, and the ratio of these two tissue types was defined as the HME T/N ratio. The prognostic significance of this ratio after surgery, along with its correlation with disease progression and metastatic potential, was evaluated. The tissues also were subjected to in situ hybridization analysis for HME. The microvessel count after immunohistochemical staining of factor VIII was used to assess angiogenesis. RESULTS: The HME T/N ratio showed an inverse correlation with the depth of the intestinal wall invasion, the lymphatic invasion, and the vascular invasion. The patients with overexpression of HME mRNA (HME T/N ratio > 1.191) significantly demonstrated better survival compared with those patients who did not show overexpression of HME mRNA. In situ hybridization identified the colorectal carcinoma cells as mainly responsible for the signal shown in Northern blot analysis. A considerable but not statistically significant lower microvessel density (MVD) was observed in the patients with HME overexpression. CONCLUSIONS: These findings demonstrate that the HME gene plays an important role in the inhibition of tumor progression in patients with colorectal carcinoma and that its overexpression is correlated closely with a better prognosis.

Aged↗
PubMed2001

Characteristics of recurrent hepatocellular carcinoma in Japan and our surgical experience.

A nationwide survey conducted by the Liver Cancer Study Group of Japan showed that approximately 85%-90% of recurrences of hepatocellular carcinoma (HCC) were in the remnant liver, and that the location of the intrahepatic recurrence was widely distributed throughout the entire liver, with 30%-40% of the recurrences on the side opposite the primary tumor, beyond Cantlie's line. In our experience, about 70% of the recurrences were seen within 2 years after surgery, and the survival rate tended to be lower as the period from the primary surgery to the recurrence was shorter. To achieve longer survival in patients with HCC, one of the most important issues is, therefore, how to prevent and control intrahepatic recurrence after surgery. Although, according to the nationwide survey, repeat hepatectomy has been performed in only 1.6% of all patients with intrahepatic recurrence, we have experienced 28 patients with repeat hepatic resection. The 1-, 3-, and 5-year survival rates from the time of re-resection were 93%, 59%, and 47%, respectively, and survival rates from the time of the initial surgery were 85% at 3 years, 62% at 5 years, and 53% at 8 years. In particular, in patients with a second primary cancer from multicentric carcinogenesis, the 5-year survival rate after the re-resection was approximately 80%. These results suggested that repeat hepatectomy should be recommended for selected patients.

Adult↗
PubMed2001

Inhibitory effect of Y-27632, a ROCK inhibitor, on progression of rat liver fibrosis in association with inactivation of hepatic stellate cells.

BACKGROUND/AIMS: Activation of hepatic stellate cells (HSCs) is a final common pathway of liver fibrosis. Recently, it has been demonstrated that the small GTPase Rho is involved in HSCs activation, and that Y-27632, an inhibitor of Rho-kinase which is an effector that acts downstream of Rho, inhibits Rho-associated effects. The objective of the current study was to investigate the inhibitory effects of Y-27632 on the activation of HSCs and the progression of liver fibrosis. METHODS: Y-27632 (1, 10, 100 microM) was added to HSCs isolated from normal rat liver. RESULTS: HSCs maintained the 'star-like' configuration of the quiescent stage in the presence of Y-27632, as well as inhibition of the expression of Na+/Ca2+ exchanger mRNA which was reported to be an indicator of HSCs activation. In addition, when Y-27632 (30 mg/kg body weight) was administered to rats with carbon tetrachloride-induced liver fibrosis, collagen deposition was inhibited, the hepatic hydroxyproline content was decreased, and the serum hyaluronic acid level was reduced. Moreover, Y-27632 reduced the number of smooth muscle alpha-actin-positive cells and transforming growth factor-beta1-positive cells, and inhibited the expression of Na/Ca2+ exchanger mRNA. CONCLUSIONS: These findings indicate that Y-27632 may be useful for the clinical management of liver fibrosis.

Amides↗
PubMed2001

RECK gene expression in hepatocellular carcinoma: correlation with invasion-related clinicopathological factors and its clinical significance. Reverse-inducing--cysteine-rich protein with Kazal motifs.

The RECK (reversion-inducing-cysteine-rich protein with Kazal motifs) gene was initially isolated as a transformation suppressor gene. It encodes a membrane-anchored glycoprotein with multiple serine protease inhibitor-like domains. The RECK gene is expressed widely in normal organs but is undetectable in many tumor-derived cell lines. When artificially expressed in such cell lines, RECK suppresses their invasive and metastatic activities. Clinical implications of these findings, however, remained undefined because of the lack of studies using fresh human tumor samples. In the present study, we have addressed this issue by analyzing the levels of RECK gene expression in hepatocellular carcinoma (HCC). RECK mRNA was detectable by RNA blot hybridization in all the tumorous and contiguous nontumorous tissues obtained from 64 patients with HCC. In 26 cases, the RECK expression in tumorous tissues was higher than that in nontumorous tissues. The expression of RECK protein in these tissues could also be demonstrated by immunohistochemistry. Patients with high RECK mRNA expression in tumorous tissues tended to show better survival (P =.02), and such tumors had a tendency to be less invasive. Univariate and multivariate analysis revealed that the RECK mRNA expression is a novel and independent variable affecting overall survival (P =.01). These findings support the hypothesis that RECK has negative effects on the invasiveness of HCC cells and suggest the feasibility of RECK mRNA as a promising prognostic molecular marker for HCC.

Adult↗
PubMed2001

Expression of METH-1 and METH-2 in pancreatic cancer.

PURPOSE: METH-1/hADAMTS-1 and METH-2/hADAMTS-8 are recently identified genes that inhibit angiogenesis, and the murine homologue, ADAMTS-1, shows metalloproteinase function. Because the significance of METH-1 and METH-2 has not been determined in solid tumors, we examined the mRNA expressions of these molecules in pancreatic cancer and hepatocellular carcinoma (HCC). EXPERIMENTAL DESIGN: METH-1 and METH-2 mRNA expressions were identified in six pancreatic cancer cell lines and were quantified by TaqMan reverse transcription-PCR in 18 paired samples of pancreatic cancer and surrounding noncancerous pancreas, and in 14 samples of pancreatic cancer. METH-1 mRNA expression was also examined in 16 pairs of HCC and cirrhotic liver. Vascularity was estimated by CD34 staining. The correlation between clinicopathological factors and METH-1 expression was additionally analyzed. RESULTS: Four of six pancreatic cancer cell lines expressed METH-1, and 1/6 expressed METH-2. METH-1 was substantially expressed in both pancreatic cancer and noncancerous pancreas, but METH-2 was not. METH-1 expression in pancreatic cancer tissue was significantly lower than that in noncancerous pancreas (P = 0.002), and a similar result was obtained between HCC and cirrhotic liver (P = 0.003). METH-1 expression did not show a significant correlation with vascularity in pancreatic cancer or in HCC. However, pancreatic cancer with higher expression of METH-1 showed significantly severe lymph node metastasis or retroperitoneal invasion (P = 0.033 and P = 0.018, respectively) and worse prognosis (P = 0.038). CONCLUSIONS: METH-1, which was initially reported to have a potent antiangiogenic effect, does not seem to be a predominant determinant of tumor vascularity in pancreatic cancer. Rather, METH-1 seems to be involved in progression of pancreatic cancer through local invasion and lymph node metastasis.

ADAM Proteins↗
PubMed2000

Role of E-cadherin in peritoneal dissemination of the pancreatic cancer cell line, panc-1, through regulation of cell to cell contact.

The present study was designed to clarify the molecules responsible for peritoneal dissemination of cancer cells. We established sublines with high (HP cells) and low (LP cells) passing activity through the membrane of a transwell chamber. The cell lines were established from the human pancreatic cancer cell line, Panc-1. LP cells demonstrated an octagonal shape and tight adhesion, whereas HP cells exhibited a spindle shape and grew with less cell-cell contact in vitro. It was found that HP cells demonstrated a high degree of peritoneal dissemination in nude mice following peritoneal injection of these cells compared to LP cells. We subsequently investigated the expression of certain adhesion molecules. Consequently, we found that LP cells exhibited a stronger expression of E-cadherin than HP cells. On the other hand, there was no difference in the expression of CD44H and beta1 integrin between these two sublines. Passing activity of LP cells through the membrane of the invasion chamber increased to nearly equal levels with HP cells following treatment with anti-human E-cadherin antibody. Moreover, transfection of mouse E-cadherin cDNA into HP cells reduced both passing activity through the membrane of the invasion chamber and peritoneal dissemination in nude mice to levels similar to that of LP cells. In conclusion, these results indicated that loss of E-cadherin facilitates both passing activity in an invasion chamber and peritoneal dissemination, playing a causative role in peritoneal dissemination of cancer cells.

Animals↗
PubMed2000

Spleen-derived dendritic cells engineered to enhance interleukin-12 production elicit therapeutic antitumor immune responses.

The major goal in cancer immunotherapy is the induction of tumor-specific T lymphocytes capable of killing tumor cells. As both dendritic cells (DCs) and interleukin-12 (IL-12) can play immunostimulatory roles in vivo, the use of a combination of these has become a promising approach. In the present study, we used a murine tumor model to examine whether spleen-derived DCs transduced with the IL-12 gene could elicit tumor-specific immune responses. BALB/c mice injected peritumorally with adenovirus-mediated IL-12 gene-transduced antigen-unpulsed DCs inhibited the growth of day 5-established subcutaneous CT26 tumors. Splenocytes from treated mice responded specifically to parental tumor cells and showed increased production of interferon gamma (IFN-gamma) and antitumor cytotoxic T-lymphocyte (CTL) activity. Increased numbers of both CD4(+) and CD8(+) T cells were detected in the treated tumors. The inhibition of tumor growth was significantly greater in mice injected with IL-12 gene-transduced DCs than in those injected with IL-12 gene-transduced fibroblasts or the IL-12 gene-encoding adenovirus itself. Taken together, these results indicate that DCs transduced with the IL-12 gene by a recombinant adenovirus are effective in inducing tumor-specific Th1 and CTL responses that inhibit the growth of established subcutaneous tumors.

Adenocarcinoma↗
PubMed2000

Implication of vascular endothelial growth factor and p53 status for angiogenesis in noninvasive colorectal carcinoma.

BACKGROUND: It still is unclear when angiogenic potential, which is believed to be a prerequisite for tumor development, is acquired. The current study was designed 1) to clarify when the phenotypic change of angiogenicity occurs during the development of colon carcinoma and 2) to investigate the possible roles of vascular endothelial growth factor (VEGF) and p53 in angiogenesis. METHODS: Colon carcinomas were classified according to the following criteria: m carcinomas were tumors in which carcinoma cells were observed within the mucosa (excluding adenomas with severe atypia) according to the World Health Organization criteria. sm carcinomas were defined by invasion into the submucosa but not into the muscularis propria. Using 27 adenomas, 26 m carcinomas, and 20 sm carcinomas, VEGF expression was analyzed with reverse transcriptase-polymerase chain reaction and immunohistochemistry. Microvessel density, VEGF, and p53 status were evaluated by immunohistochemistry. RESULTS: Neither VEGF mRNA nor VEGF protein was detected in any of the mild-to-moderate dysplastic adenomas, whereas 16 of 26 m carcinomas (62%) and all sm carcinomas exhibited VEGF protein. The microvessel density in adenomas, m carcinomas, and sm carcinomas was 3 +/- 0.55, 6.1 +/- 1.12, and 12 +/- 1.35 (0.739 mm(2) per field), respectively. In m carcinomas, positive VEGF expression was coincident with the expression of p53, and stainability for both VEGF and p53 was similar with regard to spatial distribution in tumor tissues. In m and sm carcinomas, there was a statistically significant correlation between the intensity of VEGF expression and microvessel density. CONCLUSIONS: The results of the current study demonstrated that angiogenesis develops in association with tumor progression from adenoma to noninvasive colorectal carcinoma, at least in part due to VEGF, and suggested that VEGF in m carcinomas is induced by mutant p53, although alternative mechanisms of VEGF up-regulation may exist in sm carcinomas.

Adenoma↗
PubMed2000

The suppression of small GTPase rho signal transduction pathway inhibits angiogenesis in vitro and in vivo.

Angiogenesis consists of multistep pathways such as the degradation of the matrix, proliferation of the endothelial cells, motility of the endothelial cells, formation of the cord structure and network formation of microvessels. The small GTPase Rho participates in cell motility through actin fiber polymerization. The role of the small GTPase Rho signal transduction pathway in regulating angiogenesis, however, is still unknown. In this study, we investigated the role of the small GTPase Rho signal transduction pathway in angiogenesis in vitro and in vivo using the exoenzyme, Clostridium botulinum C3 transferase, which specifically suppresses Rho and a compound, Y-27632, which suppresses p160ROCK (Rho-associated coiled-coil containing protein kinase). In this paper, we showed that the small GTPase Rho-p160ROCK signal transduction pathway played an important role in angiogenesis both in vitro and in vivo. These results suggest that inhibition of the small GTPase Rho signal transduction pathway by the p160ROCK inhibitor could be a possible new strategy for angiogenic diseases.

Amides↗
PubMed2000

Tissue factor expression in human colorectal carcinoma: correlation with hepatic metastasis and impact on prognosis.

BACKGROUND: It has been suggested that tissue factor (TF) plays an important role in tumor metastasis. Its expression in sarcoma cells was reported to up-regulate the vascular endothelial growth factor (VEGF) gene and thereby enhance tumor angiogenesis, which is essential to tumor metastasis. Although many malignant tumors have been reported to express this protein constitutively, recent clinical studies have focused mainly on the correlations among TF expression, tumor progression, and histologic grade. Therefore, to address the role of TF and the underlying mechanism of hematogenous metastasis of colorectal carcinoma, the authors analyzed the correlations among TF expression, hepatic metastasis, and VEGF gene expression in surgical specimens. Furthermore, they analyzed the prognostic significance of TF expression with respect to overall patient survival. METHODS: Expression of TF and VEGF genes in 67 advanced colorectal carcinoma specimens was studied by immunohistochemistry and Northern blot analysis, respectively. The correlations among TF expression, hepatic metastasis, and other factors were analyzed with univariate and multivariate statistics. Survival rates were calculated using the Kaplan-Meier method. RESULTS: Univariate and multivariate analyses showed TF expression to be a significant (P = 0.0001) and independent risk factor for hepatic metastasis, whereas a weak but insignificant correlation was observed between TF and VEGF gene expression. The outcomes in the TF positive group were significantly worse in all cases (P = 0.0001) and in the cases without synchronous hepatic metastasis (P = 0.0156). CONCLUSIONS: Although the precise mechanisms are unknown, TF expression is a suitable indicator of both hepatic metastasis and prognosis for colorectal carcinoma patients.

Aged↗