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Masakazu Ueda

Publications and source records attributed to Masakazu Ueda.

At least 19 recordsLinked to original sources
PubMed2007

Development of gene vectors for pinpoint targeting to human hepatocytes by cationically modified polymer complexes.

We developed a vector that might enable gene therapy of metabolic liver disease or hepatoma. Here we demonstrate the use of cationically modified biocompatible phospholipid polymer conjugated with hepatitis B surface (HBs) antigen for the specific transfer of genes into human hepatocytes. Poly(2-methacryloyloxyethyl phosphorylcholine (MPC)- co-N,N-dimethylaminoethyl methacrylate (DMAEMA)-co- p-nitrophenylcarbonyloxyethyl methacrylate(NPMA))(polyMDN) was prepared as a frame of vector. The specific expression of sFlt-1 or GFP by polyMDN conjugated with HBs containing plasmid (plasmid/polyMDN-HBs), polyMDN containing plasmid (plasmid/polyMDN), plasmid only and PBS were assessed in tumor cells (HepG2 or WiDr) in vitro and in vivo. The histological findings, organ weight changes, and degree of liver dysfunction were examined in the mice administered by several reagents. The sFlt-1 and GFP expression was observed only in the HepG2 cells transfected with sFlt-1 or GFP/polyMDN-HBs. None of the side effects mentioned above was observed. In conclusion, these results suggest that polyMDN-HBs is a human hepatocyte-specific gene delivery vector that might not have serious side effects.

Adenocarcinoma↗
PubMed2006

Retrospective analysis of outcome in 63 gallbladder carcinoma patients after radical resection.

BACKGROUND/PURPOSE: The aim of this study was to evaluate factors influencing outcome in gallbladder carcinoma after radical resection, in order to identify those patients benefiting from radical surgery. METHODS: Sixty-three patients (13 pT1, 28 pT2, 14 pT3, and 8 pT4) who underwent surgical resection for gallbladder carcinoma were retrospectively reviewed. Correlations were sought between survival and factors such as the depth of invasion (pT) including the status of infiltration of the hepatoduodenal ligament (pBinf) and liver bed (pHinf), the extent of lymph node metastasis, and other pathologic factors. RESULTS: Multivariate analysis showed that pBinf, pHinf, and lymph node metastasis were significant prognostic factors. We also analyzed survival rates for each operative procedure. There was no difference in survival between patients with or without bile duct resection for lymph node metastasis. The 5-year survival rates of pHinf-negative patients with stage 1B or more advanced disease after gallbladder bed resection or bisegmentectomy 4a,5 versus those without liver resection were 66% and 0%, respectively. Twelve patients survived for more than 5 years after surgery, including one patient undergoing HPD (liver resection with pancreatoduodenectomy) with positive lymph node metastasis; none was pBinf-positive. CONCLUSIONS: Several factyors were identified as having prognostic significance for survival in patients with gallbladder carcinomas, and we suggest that radical surgery may be indicated for selected patients with advanced disease.

Aged↗
PubMed2006

Anti-tumor effect in an in vivo model by human-derived pancreatic RNase with basic fibroblast growth factor insertional fusion protein through antiangiogenic properties.

It is thought that the export of angiogenic fibroblast growth factors (FGF) from tumors may be involved in the onset of tumor angiogenesis. To create a new active targeting drug that inhibits the tumor angiogenic process without toxicities to normal cells, human basic FGF (h-bFGF) was inserted genetically into the Gly89 position of cross-linked RNase1 (the ribonuclease inhibitor protein [RI] binding site of cross-linked human pancreatic RNase) to prevent stereospecific binding to RI. The resultant insertional-fusion protein (CL-RFN89) was active both as h-bFGF and as RNase1. Furthermore, it acquired an additional ability of evading RI through steric blockade of RI binding caused by the fused h-bFGF domain. In the present study, the effect of the resultant protein, CL-RFN89, on the antitumor response though its antiangiogenic properties was investigated in an in vivo model. Continuous systemic treatment with CL-RFN89 significantly inhibited the growth of human A431 squamous cell carcinomas in vivo. Seven days of treatment with CL-RFN89 resulted in a 58.2% inhibition of tumor growth compared with control mice (P < 0.0001). Furthermore, immunohistochemistry using a rat antimouse CD31 antibody showed that treatment with CL-RFN89 reduced tumor vascularization. These findings identify CL-RFN89 as a potent systemic inhibitor of tumor growth as a result of its antiangiogenic properties. This protein appears to be a new systemic antitumor agent.

Angiogenesis Inhibitors↗
PubMed2006

Overexpression of cyclase-associated protein 2 in multistage hepatocarcinogenesis.

PURPOSE: Hepatocellular carcinoma (HCC) associated with chronic liver disease is known to show an obvious multistage process of tumor progression. We previously identified heat shock protein 70 as a molecular marker of early HCC during investigation of expression profiling in multistage hepatocarcinogenesis. In this report, we examined cyclase-associated protein 2 (CAP2), which is also listed as an up-regulated gene in early HCC. EXPERIMENTAL DESIGN: We measured the level of CAP2 mRNA by real-time quantitative PCR. We raised a polyclonal antibody against CAP2 and we confirmed the expression of CAP2 by immunoblotting and immunohistochemistry in HCC cell lines and HCC tissues. RESULTS: According to real-time quantitative PCR, the level of CAP2 mRNA was up-regulated in early HCC when compared with noncancerous liver tissue, and it was further up-regulated in progressed HCC. We raised a polyclonal antibody against CAP2, which showed a single 53-kDa band of strong intensity in the human HCC cell lines and HCC tissues but only a weak band in the noncancerous liver tissues in Western blot analysis. Immunohistochemical examination of CAP2 revealed its significant overexpression in early HCC when compared with noncancerous and precancerous lesions and in progressed HCC when compared with early HCC. CONCLUSION: Our findings show that CAP2 is up-regulated in HCC when compared with noncancerous and precancerous lesions. This is the first report that proves that CAP2 is up-regulated in human cancers and that this is possibly related to multistage hepatocarcinogenesis.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Secretory production system of bionanocapsules using a stably transfected insect cell line.

Bionanocapsules (BNCs) are hollow nanoscale particles composed of L protein of the hepatitis B virus surface antigen that represent specific affinity for human hepatocytes. BNCs can transfer genes and drugs into human hepatocytes efficiently and specifically. BNC can be expressed in yeast cells. In this study, we developed a new L particle production system using a stably transfected insect cell line. For this purpose, we established a host-vector system using the Trichoplusia ni insect cell line. L particles were efficiently secreted by the overexpression of the L protein, which was fused to the secretion signal peptide. The concentration of L particles was reached approximately 1.7 microg/ml in 5 days during cultivation in a serum-free medium without antibiotic selective pressure. The production of L particles was maintained for at least 75 days. The secretory production of L particles facilitated their easy purification by chromatography. Furthermore, it was demonstrated that purified L particles can transfect only human hepatocytes. Therefore, an insect cell expression system is an attractive tool for the production of BNC.

Animals↗
PubMed2006

Role of steroid administration to reduce inflammation after thoracotomy in a rat surgical stress model.

BACKGROUND: Unilateral lung surgical insult can lead to bilateral pulmonary inflammation after transthoracic esophagectomy for esophageal cancer. An inflammatory response of the cytokine network induced by surgical stress followed by neutrophil sequestration is the major mechanism involved in these complications. We examined modulation of the inflammatory cytokine and neutrophil sequestration by preoperative steroid administration in a rat thoracotomy model. METHODS: Adult male rats were subjected to right thoracotomy with pulmonary compression in the surgical stress model. In the another surgical stress model, 10 mg/kg of methylprednisolone (MP) was administered 1 h before the operation intraperitoneally, and peri-operative biological effects of steroid administration to neutrophil sequestration and cytokine-induced neutrophil chemoattractant (CINC) as an inflammatory cytokine were examined. Sham-operated animals were subjected to intubation only. RESULTS: Surgical insult to the unilateral lung increased local CINC concentration followed by an increase in neutrophil sequestration, wet-to-dry weight ratio in bilateral lungs and systemic CINC concentration. Pre-treatment with methylprednisolone reduced CINC concentration as well as neutrophil sequestration and wet-to-dry weight ratio of both lungs. CONCLUSIONS: These data suggest that inflammatory changes induced by the unilateral operative procedure occur in both lungs through local inflammatory response. Pre-operative methylprednisolone administration down-regulates cytokine release and neutrophil sequestration, preventing lung edema, and possibly may act as a prophylactic treatment against acute lung injury caused by a so-called "second attack" theory.

Animals↗
PubMed2006

Anti-high-mobility group box chromosomal protein 1 antibodies improve survival of rats with sepsis.

BACKGROUND: High-mobility group box chromosomal protein 1 (HMGB1) has recently been shown to be an important late mediator of endotoxin shock, intraabdominal sepsis, and acute lung injury, and a promising therapeutic target of severe sepsis. We sought to investigate the effect of antibodies to HMGB1 on severe sepsis in a rat cecal ligation and puncture (CLP) model. METHODS: Adult male Sprague-Dawley rats underwent CLP and then were randomly divided into two groups: treatment with anti-HMGB1 polyclonal antibodies, and non-immune IgG-treated controls. The serum HMGB1 concentrations were measured at ten time points (preoperatively, and postoperatively at 4, 8, 20, 32, and 48 h and at 3, 4, 5, and 6 days). Hematoxylin-eosin staining, elastica-Masson staining, and immunohistochemical staining for HMGB1 were performed on the cecum and the lung to assess pathological changes 24 h after the CLP procedure. RESULTS: Treatment with anti-HMGB1 antibodies significantly increased survival [55% (anti-HMGB1) vs. 9% (controls); P< 0.01]. The serum HMGB1 concentrations at postoperative hours 20 and 32 of the anti-HMGB1 antibody-treated animals were significantly lower than those of the controls (P < 0.05). Treatment with anti-HMGB1 antibodies markedly diminished the pathological changes and the number of HMGB1-positive cells in the cecum and the lung. CONCLUSIONS: The present study demonstrates that anti-HMGB1 antibodies are effective in the treatment of severe sepsis in a rat model, thereby supporting the relevance of HMGB1 eradication therapy for severe sepsis.

Animals↗
PubMed2006

Gallbladder carcinoma with osteoclast-like giant cells.

Extraskeletal tumors containing multinucleated, osteoclast-like giant cells (OGCs) are uncommon. These neoplasms are most frequently reported in the breast and pancreas. Recently, some authors have suggested that carcinomas containing OGCs may represent a distinct clinicopathological entity with a more favorable prognosis. Occurrence in the gallbladder is extremely rare, with only one previous case. We report here on an additional case of gallbladder carcinoma with an infiltrate of OGCs. A 72-year-old woman presented with postprandial abdominal pain and was found to have a mass in the body of the gallbladder with direct liver invasion. Histological examination showed an adenosquamous carcinoma with an infiltrate of benign OGCs. Immunohistochemical analysis demonstrated that the giant cells were of histiocytic origin. The patient survived for 6 years without evidence of recurrence. This case adds to a small body of literature on gallbladder carcinoma with OGCs. Further studies are required to clearly define the prognostic significance of these giant cells in gallbladder cancer and the differences between adenosquamous carcinoma with OGCs and other gallbladder carcinomas (such as adenocarcinoma and squamous cell carcinoma) with those cells.

Aged↗
PubMed2006

Can endoscopic ultrasonography differentiate nonneoplastic from neoplastic gallbladder polyps?

The present study aimed to clarify the endoscopic ultrasonography (EUS) features of nonneoplastic (cholesterol polyps and adenomyomatosis) and neoplastic (adenoma and adenocarcinoma) gallbladder polyps and to evaluate the effectiveness and limitation of EUS in the differential diagnosis of these lesions. We retrospectively compared EUS images with histologic findings in 29 surgical cases with gallbladder polyps with a diameter of 10 to 20 mm. Those cases were indicated for surgery based on the findings of a sessile appearance, a solitary lesion, low echogenicity, and/or a lobulated surface. Six of 10 cholesterol polyps were atypically seen as partially or completely hypoechoic due to predominant proliferation of glandular epithelia. Nine of 10 cholesterol polyps demonstrated an aggregation of hyperechoic spots, which represented multiple granules of cholesterosis. All adenomyomatoses (n = 10) showed multiple microcysts, which corresponded to proliferated Rokitansky-Aschoff sinuses. However, three of nine neoplastic lesions (three adenomas and six adenocarcinomas) showed one of these signs due to concomitant cholesterosis (n = 2) or proliferated Rokitansky-Aschoff sinuses (n = 1). In conclusion, 69% (20/29) of gallbladder polyps larger than 10 mm that were preoperatively suspected of malignancy were nonneoplastic. An aggregation of hyperechoic spots and multiple microcysts are considered to be important predictive factors for cholesterol polyps and adenomyomatosis, respectively. However, we should caution that these findings can also occur in neoplastic polyps when they contain a concomitant nonneoplastic component (cholesterosis or proliferated Rokitansky-Aschoff sinuses).

Adenocarcinoma↗
PubMed2006

Operative indications for relatively small (2-5 cm) gastrointestinal stromal tumor of the stomach based on analysis of 60 operated cases.

BACKGROUND: Removal of the primary lesion with a clear operative margin is the standard treatment for gastrointestinal stromal tumor (GIST) of the stomach. However, there are few reports on the operative indications for relatively small GIST. METHODS: Clinicopathologic features and survival data of all 60 patients with GIST of the stomach treated at Keio University Hospital from 1993 to 2004 were analyzed. Laparoscopic wedge resection was used as the primary procedure for tumors between 2 to 5 cm. Tumors larger than 5 cm were resected by laparotomy or laparoscopy-assisted operation. RESULTS: Thirty-five lesions (58.3%) were resected by laparoscopic wedge resection, 3 by laparoscopic operation with a small skin incision and 22 by conventional open procedures. The mean size of the tumors was 42.5 mm, with a range of 18 to 150 mm and a median value of 35.5 mm. All operative margins were clear, but 1 patient had liver metastases at the time of resection of the primary lesion. The median follow-up period was 53 months and the 5-year disease-free survival rate (DFS) was 96.1%. No local recurrence or distant metastasis was encountered in patients with tumors smaller than 4 cm. A statistically significant correlation was observed between tumor size and mitotic count in this cohort (P = .010). Tumors from the intermediate- (n = 14) and high-risk (n = 10) groups as classified by the Risk Assessment Classification showed significantly worse DFS than the low-risk and very low risk group (n = 35) (89.9% vs 100% in 5-year DFS, P = .045). Even among tumors smaller than 3 cm, 2 of 14 cases (14.3%) were classified into the intermediate-risk group. CONCLUSIONS: Although a prospective randomized trial remains to be performed, this study provides additional evidence suggesting that the early removal of GIST, at 5 cm or less in size, provides better DFS than later removal of the tumor at a larger size.

Adult↗
PubMed2006

Engineered bio-nanocapsules, the selective vector for drug delivery system.

The bio-nanocapsule (BNC) is our concept of artificial hollow nanoparticles that have been designed and produced through biotechnological procedures. We proposed an empty virus-like particle, which consists of a recombinant L envelope protein of hepatitis B virus (HBV) and a lipid derived from the host cell, as an engineered BNC. Although this BNC was first developed as an immunogen of hepatitis B vaccine, the pre-S1 region in N-terminus of L envelope protein confers hepatocyte specific infectivity of HBV on the BNC. This recombinant BNC is now being developed as a novel platform of drug delivery system (DDS) vector for selective delivery.

Biomedical Engineering↗
PubMed2006

Antiangiogenic agent SU6668 suppresses the tumor growth of xenografted A-431 cells.

SU6668 is an antiangiogenic agent that acts as a tyrosine kinase inhibitor for the vascular endothelial growth factor (VEGF) receptor. We treated xenografted A-431, a human squamous cell carcinoma cell line, with SU6668 to investigate the efficacy of tumor dormant therapy using angiogenesis inhibitors for patients with squamous cell carcinoma. A-431 cells were transplanted into severe combined immunodeficient (SCID) mice. The treatment group was given SU6668 at a dose of 200 mg/kg orally twice a day for 3 weeks; the control group was given only the vehicle in the same manner and intervals. SU6668 suppressed tumor growth of A-431 cells in the xenograft model. Furthermore, tumor volume and the number of vessels were significantly reduced in the treatment group compared with those of the control. No significant differences in body weight were found between the treatment and control groups, and no toxic reactions occurred during the experiment. We concluded that this agent was safe, efficient and potentially useful for the treatment of patients with squamous cell carcinoma.

Angiogenesis Inhibitors↗
PubMed2005

Anti-angiogenic effect of an insertional fusion protein of human basic fibroblast growth factor and ribonuclease-1.

Human pancreatic ribonuclease-1 (RNase1) does not exhibit its cytotoxicity unless it is artificially internalized into the cytosol. Furthermore, once it encounters the cytosolic RNase inhibitor (RI), the activity of RNase1 is seriously reduced. To achieve the cellular targeting of RNase1 and the blocking of RI binding simultaneously, the basic fibroblast growth factor (bFGF) sequence was inserted into RNase1 at the RI binding site using a gene fusion technique. The effect of this fusion protein, CL-RFN89, on the angiogenesis, which was accelerated by FGF-FGF receptor interaction, was investigated. It was shown by using fluorescein-labeled CL-RFN89, that the binding to human umbilical vein endothelial cells (HUVECs) was dependent on the existence of the FGF receptors. In addition, CL-RFN89 inhibited the cellular growth of HUVECs in vitro and also inhibited the tube formation, using a three-dimensional tube formation assay. Furthermore, this fusion protein was shown to prevent in vivo tumor cell-induced angiogenesis, using the mouse dorsal air sac assay. These results demonstrated that CL-RFN89 inhibits angiogenesis in vitro and in vivo and that it can be expected to be a potent antiangiogenic agent.

Angiogenesis Inhibitors↗
PubMed2005

Gallstone disease after extended (D2) lymph node dissection for gastric cancer.

Few studies have reported the incidence and clinical outcomes of gallstone disease after extended (D2) lymph node dissection for gastric cancer. The present study was designed to retrospectively compare limited (D1) and D2 dissections in terms of gallstone formation, presentation of gallstones, and surgery for gallstone disease. A total of 805 Japanese gastric cancer patients (595 male, 210 female) who underwent curative resection with D1 (n = 490) or D2 (n = 315) dissection were retrospectively reviewed. Of those subjects followed for 70.5 +/- 44.3 months (range: 2-196 months), 102 (12.7%) developed gallstones. The incidence of gallstone formation was higher in the D2 group than in the D1 group (17.8% vs. 9.4%, p = 0.001). The interval between gastrectomy and detection of gallstones was shorter in the D2 group than in the Dl group (18.8 +/- 11.4 months vs. 29.4 +/- 18.3 months, p = 0.002). Of those with gallstones followed for 48.0 +/- 28.6 months (range: 1-158 months), 74 (72.5%) remained asymptomatic, and 15 (14.7%) experienced mild biliary pain. Thirteen patients (12.7%) developed recurrent biliary pain (n = 3) or biliary complications (n = 10; 6 acute cholecystitis, 3 obstructive jaundice, and 1 cholangitis), and required surgical treatment. Surgery was more frequently sought in the D2 group than in the D1 group (19.5% vs. 4.3%, p = 0.033). In conclusion, patients with D2 dissection developed gallstones more frequently and earlier than patients with D1 dissection. Of those with gallstones, patients with D2 dissection required surgery more often than patients with D1 dissection. A closer follow-up should be mandatory for gallstone disease after D2 dissection, but further studies are needed before generalizations can be made.

Aged↗
PubMed2005

Long-term survival of patients with gallbladder cancer detected during or after laparoscopic cholecystectomy.

Little evidence is available regarding long-term survival of patients with gallbladder cancer that is discovered at the time of laparoscopic cholecystectomy (LC). Therefore the present study was performed to evaluate long-term outcomes of this disease. Of 1546 patients who underwent LC for benign gallbladder disease between January 1992 and January 2002, 8 patients (0.5%) had cancers that were found during or after LC. The median follow-up period was 55 months (range: 36-142 months). The gallbladder was resected without perforation in all cases. During surgery there was a suspicion of malignancy in 6 of 8 cases. Frozen section analysis showed that 2 had TNM stage Tis tumors, 2 had T1a tumors, and 2 had T2 tumors. Two patients with T2 tumors were immediately converted to extended cholecystectomy. The final pathology revealed another 2 tumors, and demonstrated that 3 patients had Tis tumors, 3 had T1a tumors, and 2 had T2N0M0 tumors. None of the patients underwent additional surgery. All patients survived with no evidence of recurrence during the median follow-up of 55 months. In conclusion, before and during LC, we have not overlooked T2 or more advanced tumor, which requires additional procedures for curative resection. This might result in good survival. We consider that an intensive preoperative work-up and meticulous inspection of the opened gallbladder should be mandatory to detect gallbladder cancer in patients who undergo LC. At present, this is not routinely practiced.

Adult↗
PubMed2005

Left trisegmentectomy and combined resection of the inferior vena cava, without reconstruction, for giant cystadenocarcinoma of the liver.

A 54-year-old woman with giant liver cystadenocarcinoma underwent left trisegmentectomy with combined resection of the inferior vena cava (IVC) and the right hepatic vein. As a result, only the right inferior hepatic vein was preserved as a drainage vein. Because the perivertebral plexus and the azygos vein were both well developed, neither veno-venous bypass nor IVC reconstruction was performed. The developed collateral veins acted as the venous drainage pathway to maintain a stable systemic circulation. On the seventh postoperative day, portal vein flow dramatically decreased and the patient tended to liver failure. Prostaglandin E(1) (PGE(1)) was administrated via the superior mesenteric artery. The portal flow then gradually increased and liver failure was avoided. Six months after the operation, she was re-admitted due to obstructive jaundice and presented with complete stenosis of the common bile duct (CBD). The jaundice persisted and liver dysfunction progressed. The patient died seven months after the operation. The confluence of the right inferior vein and the IVC could have been deformed, causing outflow blockade. The intrinsic shunt was not good enough to act as the drainage pathway, and IVC reconstruction may have been needed.

Cystadenocarcinoma↗
PubMed2005

Primary undifferentiated spindle-cell carcinoma of the gallbladder presenting as a liver tumor.

Undifferentiated spindle-cell carcinoma (SpCC) of the gallbladder is extremely rare. There is very little information available regarding the characteristics and treatment of this disease. We herein report the unique case of a 76-year-old female patient with a primary SpCC of the gallbladder that presented as a liver tumor. Preoperative radiologic examinations showed a 5-cm liver tumor around the gallbladder bed, and irregular thickening of the gallbladder wall. The patient underwent en-bloc resection of the gallbladder and segments 4b and 5 of the liver (including the liver tumor). Microscopic findings revealed that both lesions consisted mainly of a sarcomatous spindle-shaped component. Small foci of well-differentiated adenocarcinoma cells were identified in the gallbladder mucosa. There was a gradual transition between the two different components, thereby implying that these two cell types had a common origin. Immunohistochemical studies showed that the spindle-shaped cells were epithelial in nature. The patient's postoperative course was uneventful. However, she died of recurrent liver disease 6 months after the surgery. In conclusion, we surmised that the sarcomatous spindle cells originated from a carcinomatous component in the gallbladder mucosa through dedifferentiation. Further studies are needed to better understand the characteristics of this deadly tumor, and to establish an effective therapy for it.

Adenocarcinoma↗