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Biomedical subjects

Masakazu Ueda

Publications and source records attributed to Masakazu Ueda.

At least 37 records · Page 2Linked to original sources
PubMed2005

Surgical site infection surveillance after open gastrectomy and risk factors for surgical site infection.

Surgical site infection (SSI) surveillance was examined in gastric cancer patients who had undergone an open gastrectomy between 1997 and 2003 at Keio University Hospital in Tokyo, Japan. National Nosocomial Infections Surveillance (NNIS) reports and several studies have discussed SSI risk factors, but only open gastrectomy was analyzed by regression analysis. The purpose of this study was to examine these issues by performing a regression analysis for the prediction of SSI. SSI was defined by the surgical patient component according to the NNIS system (1999) produced by the Centers for Disease Control and Prevention. Patients undergoing an open gastrectomy were followed up and monitored for SSIs. Risk factors for SSI, after all factors were considered, were studied using single and multivariate analysis. The study enrolled 984 patients who had undergoing an open gastrectomy. Using multivariate and logistic regression analysis, the duration of the operation was identified as a [corrected] risk factor for SSI at open gastrectomy. Although numerous potential risk factors in surgical patients were examined, the duration of the operation was the only significant risk factor for SSIs after open gastrectomy.

Aged↗
PubMed2005

The specific delivery of proteins to human liver cells by engineered bio-nanocapsules.

A bio-nanocapsule (BNC), composed of the surface antigen (sAg) of the hepatitis B virus, is an efficient nanomachine with which to accomplish the liver-specific delivery of genes and drugs. Approximately 110 molecules of sAg are associated to form a BNC particle with an average diameter of 130 nm. The L protein is an sAg peptide composed mainly of preS and S regions. The preS region, with specific affinity for human hepatocytes, is localized in the N-terminus. The S region following the preS has two transmembrane regions responsible for the formation of particles. In this study, the fusion of emerald green fluorescent protein (EGFP) at the C-terminus of the S region was designed to deliver proteins to human hepatocytes. Truncation of the C-terminus of the S region was required to obtain sufficient expression levels in Cos7 cells. The nanoparticles that were produced delivered EGFP to human hepatoma cells, displaying the EGFP moiety outside, or enclosing it inside. However, only a single orientation characterizes the particle, so that either type of L fusion particle could be effectively and independently separated by an antibody affinity column. The dual C-terminal topologies of the L fusion particles designed in this study could be applied to various proteins for the C-terminal moiety of the L fusion proteins, depending on the character of the proteins, such as cytoplasmic proteins, as well as cytokines or ligands to cell surface receptors. We suggest that this fusion design is the most efficient way to prepare a BNC that delivers proteins to specific cells or tissues.

Amino Acid Sequence↗
PubMed2005

Expression of basic fibroblast growth factor is associated with a good outcome in patients with squamous cell carcinoma of the esophagus.

Angiogenesis is an essential step in tumor growth and metastasis, but rather than being controlled by means of a simple mechanism, the control of tumor angiogenesis may be mediated by several angiogenic factors. We investigated the expression of basic fibroblast growth factor (b-FGF) and platelet-derived endothelial cell growth factor (PD-ECGF) in squamous cell carcinoma of the esophagus in order to clarify the mechanism of angiogenesis. Expression of b-FGF and PD-ECGF was immunohistochemically investigated in tissue specimens from the tumors of 79 patients with squamous cell carcinoma of the esophagus who underwent curative esophagectomy without preoperative chemotherapy or radiation therapy, and the relationship between expression of b-FGF/PD-ECGF, microvessel density (MVD), and clinicopathological background factors was assessed. Tumor cells that expressed b-FGF were found in 41 patients (51.9%), and tumor cells that expressed PD-ECGF were found in 57 patients (72.2%). Although the mean vascular density (47.9/mm(2)) of b-FGF-positive tumors was significantly lower than that (67.2/mm(2)) of b-FGF-negative tumors (p=0.014), the difference between the 56.0/mm2 in PD-ECGF-positive tumors and 60.3/mm2 in PD-ECGF-negative tumors was not significant. Although the survival rate of patients with b-FGF-positive tumors was significantly higher than those with b-FGF-negative tumors (p=0.033), there was no significant difference between the survival rates of patients with PD-ECGF-positive and -negative tumors (p=0.580). Expression of b-FGF may be associated with promotion of angiogenesis and a good prognostic factor in squamous cell carcinoma of the esophagus.

Adult↗
PubMed2004

Antitumor effect induced by dendritic cell (DC)-based immunotherapy against peritoneal dissemination of the hamster pancreatic cancer.

Establishing a method to control peritoneal dissemination is one of the most pressing issues in the postsurgical treatment of pancreatic cancer. In the present study, we investigated the effect of dendritic cell (DC)-based immunotherapy on peritoneal disseminations of hamster pancreatic cancer cells, PGHAM-1. After the orthotopically inoculation of 2 x 10(6) PGHAM-1 cells, DC pulsed with PGHAM-1-derived tumor lysates, DC alone or PBS as a vehicle was injected intraperitoneally (i.p.) three times at weekly intervals. The group treated with DC or DC+lysate was found to have smaller disseminated tumors than the vehicle-treated. In addition, mean survival time in the DC+lysate groups was significantly longer than the PBS group. These findings suggested that DC-based immunotherapy might be efficient for the treatment of peritoneal disseminations of the pancreatic cancer.

Animals↗
PubMed2004

Identification of an epigenetically silenced gene, RFX1, in human glioma cells using restriction landmark genomic scanning.

To identify the CpG islands differentially methylated in human glioma, we performed restriction landmark genomic scanning with a CpG methylation-sensitive enzyme. We found 12 spots, the intensity of which was entirely lost or decreased in both the human glioma tissues examined as compared with that in matched normal lymphocytes, indicating aberrant methylation of these CpG islands in gliomas. The expression of RFX1, one of the genes associated with the methylated CpG islands, was frequently decreased in human glioma cell lines and tissues. We also demonstrated that the isolated CpG island located in the seventh intron of the RFX1 gene had enhancer activity and was hypermethylated in all of the glioma tissues and cell lines analysed, but not in normal brains or lymphocytes. Treatment of glioma cells with a demethylating agent, 5-azacytidine, resulted in the expression of RFX1, indicating that the silencing of the RFX1 gene may be attributable to its methylation. RFX1 has been implicated in transcriptional downregulation of the proto-oncogene c-myc. By expression of the RFX1 gene, the cellular proliferative activity of glioma cells was suppressed. Taken together, these results suggest that the RFX1 gene may be epigenetically silenced in human gliomas and involved in glioma tumorigenesis.

Base Sequence↗
PubMed2004

Comparison of K-ras point mutation distributions in intraductal papillary-mucinous tumors and ductal adenocarcinoma of the pancreas.

Intraductal papillary-mucinous tumors (IPMT) consist of cells with varying histologic degrees of severity and exhibit multiple tumor loci; however, whether or not these lesions exhibit the same genetic changes has not been clarified. To investigate this point, we analyzed K-ras mutations in multiple IPMT lesions from each patient enrolled in our study and compared our findings to those for patients with ductal adenocarcinoma of the pancreas (DC). Twenty IPMT specimens and 7 DC specimens were resected, microdissected and analyzed for the presence of K-ras mutations. The mutated genes were then sequenced using a genetic analyzer. K-ras mutations were observed in 80% of IPMT and 100% of DC patients. More than 2 types of K-ras mutation were observed in the main tumors of 43.8% of IPMT and 0% of DC patients. K-ras mutations in peritumoral and separated lesions were observed in 66.7% and 62.5% of IPMT patients, respectively. At least one identical mutation between the main tumor and the peritumoral or separated lesions was recognized in all of the IPMT patients with those lesions. Different mutations from those in the main tumor were observed in 40% of IPMT patients with separated lesions. The survival curve of IPMT-carcinoma patients with more than 2 types of K-ras mutation in the main tumor was better than that with one type of K-ras mutation. IPMT patients exhibit a remarkably genetic heterogeneity in main tumor and have good prognosis.

Adenocarcinoma↗
PubMed2004

Loss of p16INK4a expression is associated with vascular endothelial growth factor expression in squamous cell carcinoma of the esophagus.

Vascular endothelial growth factor (VEGF) expression has been suggested to correlate with intratumoral microvessel density, tumor advancement and prognosis in esophageal squamous cell carcinoma (ESCC). Previous studies have showed that disruption of cell cycle regulator p16 is related to oncogenesis and tumor progression in ESCC. We hypothesized that VEGF expression in ESCC is reflected by abnormalities in the p16(INK4a) gene. To clarify the regulatory role of p16(INK4a) in VEGF expression in vitro, we transferred the p16(INK4a) gene into a p16(INK4a)-deleted ESCC cell line and observed changes in VEGF expression. Furthermore, we immunohistochemically assessed the expression of the cell cycle regulators (p16, p53 and RB) and VEGF in 90 surgically resected specimens of ESCC. Introduction of p16(INK4a) cDNA by the p16 expression vector significantly suppressed cell proliferation in the p16(INK4a)-deleted cell line TE8 (p < 0.0001). VEGF secretion by TE8 cells transfected with the p16(INK4a) vector was significantly suppressed as compared to non-transfected TE8 cells (p < 0.0001) and TE8 cells transfected with a control vector (p = 0.0015). The immunohistochemical studies of ESCC primary tumor specimens showed that loss of p16 expression was significantly correlated with VEGF-positive expression (p = 0.0004). The cumulative postoperative survival rate in the group with p16-positive and VEGF-negative expression was significantly higher than in the other groups. Neither p53 nor RB expression had any impact on outcome. Aberrant p53 expression tended to be associated with VEGF expression, but the trend did not reach statistical significance. Our study demonstrated that VEGF expression was correlated with p16 expression in ESCC. Our results suggest that p16 may have a regulatory role in VEGF expression in ESCC.

Aged↗
PubMed2004

Intraductal growth of a nonfunctioning endocrine tumor of the pancreas.

Intraductal growth of nonfunctioning endocrine tumors of the pancreas may be very rare, and our survey of literature shows only two cases have been described. We report a case of a 43-year-old man with a nonfunctioning endocrine tumor of the pancreas that uniquely grew within the lumen of the main pancreatic duct (MPD) without ductal involvement and completely obstructed the MPD. Endoscopic ultrasonography (EUS) and endoscopic retrograde cholangiopancreatography (ERCP) were very helpful to delineate the intraductal growth of the tumor and to determine the resection line of the pancreas. A nonfunctioning pancreatic endocrine tumor is important to consider on differential diagnoses when complete obstruction of the MPD is demonstrated on ERCP. It is speculated that the tumor originated from precursor cells of the pancreatic duct or islet cells adjacent to the MPD and slowly proliferated within the lumen of the MPD.

Adult↗
PubMed2004

The influence of platelets on the promotion of invasion by tumor cells and inhibition by antiplatelet agents.

OBJECTIVE: Using a chemoinvasion assay, we show that platelets promote invasiveness of 5 pancreatic adenocarcinoma cell lines. METHODS: Gelatin zymography and Western blot analysis were performed to detect metalloproteinase-9 (MMP-9) secreted from tumor cells in the presence or absence of platelets. The effects of antiplatelet agents on the invasiveness of tumor cells and the secretion level of MMP-9 were evaluated. RESULTS: The number of traversed tumor cells significantly increased when incubated with platelets compared without platelets in all cell lines. The MMP-9 band was detected in all tumor cell lines, and the intensity was obviously greater in conditions of incubation with platelets than without. In the experiment of antiplatelet agents effects, it was confirmed that invasiveness of tumor cells significantly decreased following incubation with cilostazol depending on the concentration in spite of the presence of platelets. The level of MMP-9 also significantly decreased in the ELISA analysis. CONCLUSIONS: These data mean platelets activate invasiveness of tumor cells because of enhanced MMP-9 secretion. Furthermore, anti-platelet drugs may inhibit invasiveness of tumor cells due to decreased MMP-9 secretion, and this inhibition may lead to the suppression of tumor cell invasion. We propose that antiplatelet agents are applicable in clinical treatment to inhibit metastasis of malignant tumor cells.

Adenocarcinoma↗
PubMed2004

Squamous cell carcinoma of the liver originating from non-parasitic cysts after a 15 year follow-up.

Squamous cell carcinoma is an extremely rare primary liver tumour. A 42-year-old man presented at our hospital on 19 February 1986, with pain in the right upper quadrant of the abdomen and general fatigue, and reported an 8 year history of this complaint. Ultrasonography showed four cystic masses in the liver with a maximum diameter of 15 cm, one of which contained a solid component. A computed tomography (CT) scan confirmed a huge, predominantly cystic, mass in the liver with a small solid component and irregular wall. Calcifications were seen in the solid components. On 22 April 1986, a laparotomy was performed but the masses were too large to be removed. During 15 years of follow-up after the laparotomy, there had been no change seen in his abdominal CT scan. He subsequently arrived at our hospital again on 10 July 2001 with loss of appetite and of body weight. A CT scan showed a cyst in the liver of 25 cm in diameter with calcification that had a large solid part invading the liver. A post-mortem pathological dissection showed multiple cysts, the largest of which was 25 cm in diameter. They had large solid parts with calcification invading the liver. There were widespread metastatic lesions. Microscopic examination showed the tumour to be a well differentiated squamous cell carcinoma. To the best of our knowledge, this is the first report of a squamous cell carcinoma arising from 15 multiple non-parasitic hepatic cysts after a 15 year follow-up. Furthermore, 23 years had passed since the patient's symptoms appeared for the first time.

Adult↗
PubMed2004

Novel tissue and cell type-specific gene/drug delivery system using surface engineered hepatitis B virus nano-particles.

The hepatitis B virus (HBV) surface antigen (HBsAg) L particle is a hollow nano-scale particle. HBsAg L particles have many properties that make them useful for in vivo gene transfer vectors and drug delivery systems. Gene therapy so far has required the in vivo pinpoint delivery of genetic materials into the target organs and cells. Gene transfer by HBsAg L particles might be an attractive method, since their tropism is the same as that of HBV. The HBsAg L particles are able to deliver therapeutic payloads with high specificity to human hepatocytes. In addition, the specificity of L particle can be altered by displaying various cell-binding molecules on the surface. Our results indicate that the L particle is suitable for a cell- and tissue-specific gene/drug transfer vector. In this review, we discuss HBsAg L particles as a gene/drug transfer vector and its potential for the treatment of infectious diseases.

Drug Delivery Systems↗
PubMed2004

[Liver regeneration after resection: molecular and cellular mechanism].

It has been well established that the liver can regenerate after resection. Liver regeneration is a fundamental mechanism by which the liver responds to injury. This review article discusses molecular and cellular mechanism of liver regeneration, including growth factors and cytokines in the initiation and regulation of liver regeneration, the importance of the liver extracellular matrix and its dynamic effect on hepatocyte growth, and finally, stem cell biology in liver regeneration.

Animals↗
PubMed2003

Nanoparticles for the delivery of genes and drugs to human hepatocytes.

Hepatitis B virus envelope L particles form hollow nanoparticles displaying a peptide that is indispensable for liver-specific infection by hepatitis B virus in humans. Here we demonstrate the use of L particles for the efficient and specific transfer of a gene or drug into human hepatocytes both in culture and in a mouse xenograft model. In this model, intravenous injection of L particles carrying the gene for green fluorescent protein (GFP) or a fluorescent dye resulted in observable fluorescence only in human hepatocellular carcinomas but not in other human carcinomas or in mouse tissues. When the gene encoding human clotting factor IX was transferred into the xenograft model using L particles, factor IX was produced at levels relevant to the treatment of hemophilia B. The yeast-derived L particle is free of viral genomes, highly specific to human liver cells and able to accommodate drugs as well as genes. These advantages should facilitate targeted delivery of genes and drugs to the human liver.

Animals↗
PubMed2003

Cell-cycle regulators and the Ki-67 labeling index can predict the response to chemoradiotherapy and the survival of patients with locally advanced squamous cell carcinoma of the esophagus.

BACKGROUND: We investigated whether aberrant p53 and p16 expression, the Ki-67 labeling index (LI), and int-2/cyclin D1 gene amplification predict the response to chemoradiotherapy (CRT) in patients with locally advanced esophageal squamous cell carcinoma (ESCC). METHODS: p53 and p16 expression status, the Ki-67 LI, and int-2/cyclin D1 amplification were assessed by immunohistochemical staining and slot blot analysis in pretreatment endoscopic biopsy specimens of 41 patients with T4 or M1 Lym (distant lymph node metastasis) ESCC. All patients received a course of chemotherapy (5-fluorouracil and cisplatin) with radiotherapy. RESULTS: The CRT therapeutic response rate was 71%, and resection after CRT was successful in 15 of the cases in which the CRT effect was significant. The cumulative survival rate after CRT in the p53-negative patients was significantly higher than in the p53-positive patients (P =.037). The mean Ki-67 LI in the CRT response cases was significantly higher than in the CRT no-response cases (P =.023). Multivariate regression analysis revealed high Ki-67 LI to be an independent variable linked to a pathologic complete response to CRT (P =.033). The cumulative survival rate after CRT in the group that was p53-negative and int-2/cyclin D1 amplification-positive was significantly higher than in the other groups (P =.008). CONCLUSIONS: Evaluating predictive factors in pretreatment endoscopic biopsy specimens may allow selection of more suitable multimodal treatment for ESCC patients and improve their quality of life.

Adenocarcinoma↗
PubMed2002

Correlation of postoperative recurrence in hepatocellular carcinoma with demethylation of repetitive sequences.

Restriction landmark genomic scanning (RLGS) was utilized to identify novel genomic alterations in hepatocellular carcinoma (HCC). Thirty-one HCC samples were examined by RLGS. Two high intensity spots were common to several RLGS profiles of different HCCs. Nucleotide sequencing and homology search analysis showed that these spots represented repetitive sequences, Human tandem repeat sequence (Genbank, L09552) and centromeric NotI cluster (Genbank, Y10752). These intensified signals were attributable to the occurrence of demethylated areas in the recognition sequence of the NotI site of the corresponding fragments. The intensity of these spots in the RLGS profile reflects their degree of demethylation, which was significantly correlated with postoperative recurrence, even in patients regarded as belonging to the good prognosis group by conventional prognostic factors. Multivariate analysis showed that the intensities of the two spots retained independent prognostic value. This is a new type of predictive factor for HCC based on epigenetic changes in hepatocarcinogenesis, and in the future it is expected to be of great value in making preoperative diagnosis and selecting postoperative therapy.

Adult↗
PubMed2002

MYEOV, a gene at 11q13, is coamplified with CCND1, but epigenetically inactivated in a subset of esophageal squamous cell carcinomas.

DNA amplifications at 11q13 are frequently observed in esophageal squamous cell carcinoma (ESC) and correlate with a malignant phenotype. Although this amplicon spans a region of several megabases and harbors numerous genes, CCND1 and EMS1 are thought to be the relevant candidates in ESC. We investigated whether the putative transforming gene MYEOV, mapping 360 kb centromeric to CCND1 and activated concomitantly with CCND1 in a subset of t(11;14)(q13;q32) positive multiple myeloma cell lines, represents a target of 11q13 amplification in ESC. To evaluate the role of MYEOV in ESC, we tested 31 ESC cell lines and 48 primary tumors for copy number levels of MYEOVand demonstrated that MYEOV was always coamplified with CCND1. However, MYEOV expression levels correlated only inconsistently with DNA amplification data. Treatment with the demethylating agent 5-aza-2'-deoxycytidine restored MYEOV expression in a subset of cell lines exhibiting DNA amplification without high MYEOV expression, suggesting that MYEOV is transcriptionally silenced by a DNA methylation mechanism in most of the latter cell lines. Our results indicate that MYEOV is a coamplified gene with CCND1 at 11q13, but its activation is sometimes inhibited by an epigenetic mechanism.

Azacitidine↗