Impact of heparin neutralization by protamine on restenosis after coronary stent implantation.
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Aged↗
Biomedical subjects
Shinji Tanaka
Publications and source records attributed to Shinji Tanaka.
Stage and region dependent expression of a radial glial marker in commissural fibers in kindled mice.
Amygdala kindling is regarded as a model of temporal lobe epilepsy in humans because of many points of similarity. In amygdala kindling, bilateralization of epileptic seizures follows from the accumulation of stimulation and commissural fibers may play a role in this process. However, new progenies of cells following amygdala kindling have not been reported and the precise nature of how bilateralization occurs is not clear. In the present study, we aim to clarify the emergence of radial glia during the progress of amygdala kindling in mouse brain. For this purpose, immunohistochemical staining for 3CB2, which is a specific marker of radial glia, was employed. Immunoreactivity for 3CB2 was observed in the forceps minor, radiation of trunk and forceps major regions at Clonus 3 and more strongly at Clonus 5. In the forceps major, the cingulate gyrus showed immunopositive staining at Clonus 3, but the corpus callosum and alveus hippocampi showed staining only at Clonus 5. In the fimbria hippocampus, the anterior commissure posterior showed staining at Clonus 5. However, the anterior commissure anterior was not stained at the stage progressed to Clonus 5. These findings indicate stage and region dependent expression of progenitor cells in commissural fibers and suggest that these changes may accompany the formation of new circuits in seizure progression during amygdala kindling.
Amygdala↗
Expression of vascular endothelial growth factor (VEGF)-C and VEGF-D in early gastric carcinoma: correlation with clinicopathological parameters.
In this study, we investigated whether expression of vascular endothelial growth factor (VEGF)-C and/or VEGF-D correlates with clinicopathological features of human gastric carcinoma. We immunohistochemically examined the expression of VEGF-C and VEGF-D in 140 archival surgical specimens of submucosally invasive gastric carcinoma. Of these specimens, 32 (22.9%) and 12 (8.6%) showed intense VEGF-C and VEGF-D immunoreactivity in cancer cells, respectively. VEGF-C immunoreactivity was associated with histological type, lymphatic invasion, lymph node metastasis, and microvessel density. No association was identified between VEGF-D immunoreactivity and clinicopathological variables. These results suggest that VEGF-C is a dominant regulator of lymphangiogenesis in early-stage human gastric carcinoma.
Carcinoma↗
A classification system of echogenicity for gastrointestinal neoplasms.
BACKGROUND AND AIMS: To confirm the utility of a newly-devised endoscopic ultrasonography (EUS) echogenicity classification system, which is based on the normal five-layer structure of the gastrointestinal wall, for the differential diagnosis of gastrointestinal neoplasms. METHODS: A total of 275 patients with gastrointestinal disease detected by endoscopy, 53 with submucosal tumor (22 esophageal, 27 gastric, and 4 duodenal), 208 with cancer (58 esophageal, 150 gastric), and 14 with gastric malignant lymphoma, were examined. In each case, we performed standard EUS with 7.5, 12, or 20 MHz to evaluate the echogenicity of the lesion. Echogenicity was classified into seven levels that is based on the echogenicity of the normal five-layer structure of the gastrointestinal wall. The levels are stratified from anechoic (level 0) to hyperechoic (level 6), muscularis propria and deep mucosa being referred to as level 2 and level 4, respectively. Level 6 was equivalent to or higher than the echogenicity of submucosa. RESULTS: EUS findings revealed several distinct echogenicities among the diseases. In submucosal tumor, levels 0, 2, and 6 were observed only in patients with cyst, myogenic tumor, and lipoma, respectively. In malignancies, levels 0, 5, and 6 were not observed in this study. The echo level of malignant lymphoma was markedly lower than that of epithelial cancer. CONCLUSION: Our classification system of echogenicity can be a useful method in the differential diagnosis of gastrointestinal neoplasms.
Adult↗
Oncogenic role of the frizzled-7/beta-catenin pathway in hepatocellular carcinoma.
BACKGROUND/AIMS: The molecular mechanisms of hepatocarcinogenesis remain largely unknown. Previous studies suggest that activation of the Wnt/beta-catenin pathway is important during hepatocyte transformation but the role of Frizzled receptor (FZD) in this process has not been defined. Here we investigate activation of this pathway by FZD using transgenic hepatocellular carcinoma (HCC) murine models. METHODS: We employed single (c-myc, SV40-Tag) and established double [insulin receptor substrate-1 (IRS-1/c-myc) and hepatitis Bx protein (X/c-myc)] transgenic lines and all developed HCC. Expression of 9 FZD was measured by real time RT-PCR and Western blot analysis. Phosphorylation and cellular accumulation of beta-catenin were assessed in both dysplastic tissue and tumors. We investigated the effect of a dominant negative (DN) FZD7 on TCF transcriptional activity in a SV40 derived HCC cell line. RESULTS: FZD7 was highly overexpressed at the mRNA and protein level(s) in HCC and occurred in dysplasia. Upregulation of FZD7 was associated with reduced phosphorylation of beta-catenin and led to nuclear accumulation in HCC tumors. Ectopic expression of a DN FZD7 construct decreased TCF transcriptional activity in tumor cells. CONCLUSIONS: These observations suggest that upregulation of FZD7 receptors in association with activation of the canonical Wnt/beta-catenin pathway is a common molecular event in HCC.
Animals↗
Quantitative analysis of lymphangiogenic markers for predicting metastasis of human gastric carcinoma to lymph nodes.
The spread of tumor cells to regional lymph nodes is an early event of gastric cancer metastasis. In our study, we assessed the expression of lymphangiogenic factors and lymphatic endothelial markers in gastric carcinoma tissues and compared expression levels with the status of lymph node metastasis. We also examined the correlation between lymphatic vessel density (LVD) in primary tumors and lymph node metastasis. Paired biopsy samples (tumor and corresponding normal mucosa) of gastric tissue were obtained from 39 patients with gastric carcinoma. The expression of VEGF-C, VEGF-D, VEGFR-3 and podoplanin mRNAs was assessed by real-time quantitative PCR. The expression of VEGF-C (but not of VEGF-D) was significantly greater in patients with lymph node metastasis than in those without metastasis. The expression of lymphatic endothelial markers VEGFR-3 and podoplanin was also significantly greater in the node-positive group. LVD, as assessed by immunohistochemistry for podoplanin, was correlated with lymph node metastasis. These results indicate that quantitative analysis of lymphangiogenic markers in gastric biopsy specimens may be useful in predicting metastasis of gastric cancer to regional lymph nodes.
Biomarkers, Tumor↗
Catalytic dehydrative allylation of alcohols.
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Journal Article↗
The newly established human hepatocyte cell line: application for the bioartificial liver.
BACKGROUND/AIMS: Human hepatocyte cell lines are reported to lose many of their biochemical functions in a hybrid artificial liver support system (HALSS). Differentiation therapy is useful to up-regulate liver function. METHODS: The human hepatoblastoma cell line HepG2 was transfected with HSV/tk gene. Albumin synthesis and ammonia removal activity were evaluated when HepG2/tk was cultured with histone deacetylase inhibitor (FR228) and peroxisome proliferator activated receptor-gamma ligand (pioglitazone). To investigate the function of HepG2/tk in vivo, cell transplantation for 90% hepatectonized rats was conducted. RESULTS: We established stable cell lines which expressed HSV/tk and were sensitive to gancyclovir in vitro and in vivo. Both albumin synthesis rate and ammonia removal rate improved for HepG2/tk incubated with FR228 and pioglitazone for 3 days, which induced nuclear transport of p21. Rats with intrasplenic injection of HepG2/tk precultured for 3 days with FR228 and pioglitazone survived significantly longer than the control rats. The ammonia and total bilirubin concentrations were significantly lower in the test group than in the control group. The injection of gancyclovir inhibited the prolonged survival of the rats with precultured HepG2/tk. CONCLUSIONS: HepG2/tk is safe as well as enhancing high levels of liver function. It will be a potential cell source for HALLS in the future.
Animals↗
p53 mutation profiling of multiple esophageal carcinoma using laser capture microdissection to demonstrate field carcinogenesis.
Inactivation of the p53 tumor suppressor gene is one of the most frequent genetic alterations observed in human esophageal carcinomas. In patients with esophageal carcinoma, one of the significant pathological features of the tumor is the presence of multiple lesions within the esophagus. However, the molecular mechanisms involved in the occurrence of multiple lesions have remained elusive. To characterize p53 alterations in multiple esophageal carcinomas and to study their roles in carcinogenesis, we performed p53 immunohistochemical and p53 mutation analyses using laser capture microdissection on surgically resected human esophageal carcinomas from 11 patients: 9 patients with multiple esophageal carcinomas, 1 with an intramural metastasis lesion within the esophagus and 1 with an intraepithelial carcinoma lesion contiguous to the main lesion. In each of the patients with multiple esophageal carcinomas, we examined samples from 1 main lesion and 1 representative concomitant lesion. Molecular analyses of samples from fresh-frozen normal tissues and tumor tissues of the main lesion (whole tumor) were also performed by the same method. p53 protein accumulation was observed in 16 (72.7%) of 22 lesions from the 11 cases. No p53 mutation was found in normal esophageal tissues. In the 9 cases of multiple esophageal carcinomas, point mutations were detected in the whole tumor in 1 (11.1%) case, in the microdissected tumor samples of main lesions in 3 (33.3%) cases and in the microdissected tumor samples of concomitant lesions in 3 (33.3%) cases. For the microdissected tumor samples, there was a 54.5% (12/22) concordance rate between the results of immunostaining and molecular analysis. In the 8 cases of whole tumors in which a p53 mutation was not observed, 2 cases revealed p53 mutation in the microdissected tumor samples of the main lesion. All 6 cases of multiple esophageal carcinomas that showed a p53 mutation in the microdissected tumor sample had a discordant p53 mutational status between the main and concomitant lesions. In contrast, both the intramural metastasis lesion and the intraepithelial carcinoma contiguous to the main lesion showed p53 mutational patterns identical to those of the main lesions. In conclusion, the analysis of microdissected DNA by laser capture microdissection is useful for characterizing the heterogeneity of the p53 gene mutation in multiple carcinoma lesions that cannot be accurately analyzed in whole esophageal tumor DNA. The finding of different p53 gene mutations among multiple esophageal carcinoma lesions suggest further evidence of multicentric or field carcinogenesis of the human esophagus.
Carcinoma in Situ↗
Infliximab therapy for Crohn's disease in a patient with chronic hepatitis B.
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Adolescent↗
Surgical outcome of patients with hepatocellular carcinoma originating in the caudate lobe.
BACKGROUND: Hepatocellular carcinoma (HCC) originating in the caudate lobe is rare, and the treatment for this type of carcinoma is difficult because of its unique anatomic location. METHODS: This retrospective study assessed the surgical outcome of patients with caudate lobe HCC. There were 20 cases of HCC originating in the caudate lobe among 435 patients with primary HCC who underwent hepatic resection in our department from 1990 to 2002. The caudate tumors were located in the Spiegel lobe in 3 patients, the paracaval portion in 15 patients, and the caudate process in 2 patients. Surgical procedures consisted of limited resection of the caudate lobe in 6 patients and extended caudate lobectomy in 14 patients. Recurrence was recognized in 12 patients, including 8 patients with multiple intrahepatic recurrences, 1 with peritoneal dissemination, and 1 with lymph node metastasis. RESULTS: There was no significant difference in postoperative survival rate between patients who underwent limited resection of the caudate lobe and those who underwent extended caudate lobectomy. Compared with 415 patients with HCC originating in other locations, the 20 patients with caudate lobe HCC showed significantly more intraoperative blood loss (P<.05), longer operation time (P<.0001), and more postoperative complications (P<.005). Intrahepatic recurrence was more frequent in the caudate lobe HCC compared with HCC originating in other locations (40% vs 17.6%; P<.05). There was a significantly poor survival rate in the postoperative patients with caudate HCC (25.9% vs 54.1% for five-year survival; P=.01). Intrahepatic multiple recurrences were frequently recognized in the patients with caudate lobe HCC, indicating no significance for extended caudate lobectomy. CONCLUSIONS: Because of the relatively poor prognosis in patients with caudate lobe HCC, adjuvant therapy combined with surgical operation should be considered.
Aged↗
Multiple carcinoid tumors of the ileum preoperatively diagnosed by enteroscopy with the double-balloon technique.
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Carcinoid Tumor↗
Single dose of OCH improves mucosal T helper type 1/T helper type 2 cytokine balance and prevents experimental colitis in the presence of valpha14 natural killer T cells in mice.
BACKGROUND AND AIMS: Valpha14 natural killer T (NKT) cells seem to play important roles in the development of various autoimmune diseases. However, the pathophysiologic role of NKT cells in inflammatory bowel disease remains unclear. To clarify the mechanism by which the activation of NKT cells mediates protection against intestinal inflammation, we investigated the antiinflammatory role of specifically activated Valpha14 NKT cells by glycolipids in a mouse experimental model of colitis induced by dextran sulfate sodium (DSS). METHODS: Colitis was induced in C57BL/6 mice by the oral administration of 1.5% DSS for 9 days. A single dose of OCH or alpha-galactosylceramide, a ligand for NKT cells, was administered on day 3 after the induction of colitis. Body weights and colonic mucosal injury were assessed in each glycolipid-treated group. Interferon-gamma and interleukin-4 levels in the supernatants from colonic lamina propria lymphocytes (LPLs) were measured by enzyme-linked immunosorbent assay. RESULTS: The administration of a single dose of OCH attenuated colonic inflammation, as defined by body weights and histologic injury. The protective effects of OCH could not be observed in Valpha14 NKT cell-deficient mice. In vivo treatment with OCH had improved the interferon-gamma/interleukin-4 ratio from colonic LPLs on day 9 after DSS treatment. CONCLUSION: The present data indicated that the activation of Valpha14 NKT cells by OCH plays a pivotal role in mediating intestinal inflammation via altered mucosal T-helper type 1/type 2 responses. Therapeutic strategies that are designed to activate specifically Valpha14 NKT cells may prove to be beneficial in treating intestinal inflammation.
Animals↗
Cardiac glands hyperplastic polyp of the stomach.
Reported herein is a very rare polyp in the gastric cardia of a 49-year-old man. He was referred because of a polyp detected by upper gastrointestinal examination in an affiliated hospital. Endoscopic examination revealed a polyp-like submucosal tumor. Endoscopic ultrasonography revealed minute cystic dilatations and thickening of the submucosal layer. Accordingly, a preliminary diagnosis of cardiac gland hyperplasia was made. The lesion was removed successfully by snare polypectomy. Observed macroscopically, the polyp was 30 mm in diameter and covered with normal gastric mucosa. Examined histologically, the polyp comprised a hyperplastic submucosal cardiac gland.
Cardia↗
A combination of the Helicobacter pylori stool antigen test and urea breath test is useful for clinical evaluation of eradication therapy: a multicenter study.
BACKGROUND: Helicobacter pylori stool antigen (HpSA) test is a new tool for evaluating the H. pylori infection. The present study was carried out to investigate the clinical usefulness of the HpSA test in the evaluation of eradication therapy by comparing it with the (13)C-urea breath test (UBT). METHODS: One hundred and five patients received eradication therapy for H. pylori. After more than 8 weeks, the success of the therapy was evaluated by the HpSA test and the UBT. Concordant results were regarded as a final diagnosis, but when the results were discordant, histological examination was carried out. RESULTS: Of the 105 patients receiving eradication therapy for H. pylori, 25 patients were regarded as H. pylori positive by the UBT and and 20 patients were regarded as H. pylori positive by the the HpSA test. Nine patients (8.6%) showed discordant results (seven cases with UBT(+) and HpSA(-), and two with UBT(-) and HpSA(+)). Five cases out of nine were ultimately judged as having a false-positive result of the UBT, and in these cases the UBT values were relatively low (below 10 per thousand). The final diagnostic accuracies of the UBT and the HpSA test were 94.3% (88.0-97.9%; 95% CI) and 97.1% (91.9-99.4%), respectively. When we used the HpSA test in cases with weakly positive UBT values, we were able to diagnose the correct status of H. pylori infection after eradication in 99% of all patients (94.8-100.0%). CONCLUSION: The HpSA test is a useful tool for the evaluation of eradication therapy and a combination of the HpSA test and UBT is clinically recommended.
Adult↗
Somatic mutations of mitochondrial DNA in digestive tract cancers.
BACKGROUND: Somatic mutations of mitochondrial DNA (mtDNA) have been reported to play an important role in the carcinogenesis of several human cancers. However, there are few reports on mtDNA mutations in digestive tract cancers, including esophageal, gastric and colorectal cancers. The present study examined somatic mtDNA mutations in these cancers. METHODS: Samples of 82 esophageal cancers, 96 gastric cancers and 138 colorectal cancers were collected. Mutations in the D310 mononucleotide repeat of mtDNA were examined by microsatellite assay. RESULTS: Frequencies of mtDNA mutations were similar in each digestive tract cancer: 14% (7/51) in esophageal cancers, 15% (14/94) in gastric cancers and 8% (11/133) in colorectal cancers. There were no significant relationships between mtDNA mutations and clinicopathological features, such as patient age or sex, tumor location, depth of tumor invasion and lymph node metastasis in each digestive tract cancer. CONCLUSIONS: The results suggest that mtDNA mutations play a role in the development but not progression in each digestive tract cancer, and that the role of mtDNA mutations might be similar among the digestive tract cancers.
Aged↗
Subsieve-size agarose capsules enclosing ifosfamide-activating cells: a strategy toward chemotherapeutic targeting to tumors.
Localized activation of the prodrug ifosfamide in or close to tumors by implanting encapsulated ifosfamide-activating cells is an efficacious strategy for tumor therapy. The aim of this study was to evaluate the feasibility of subsieve-size agarose capsules for enclosing the cells in this application. Compared with many conventional microcapsules, subsieve-size agarose capsules are about one-tenth the size and have both higher mechanical stability and allow better molecular exchangeability than other systems. Cells that have been genetically modified to express cytochrome P450 2B1 enzyme were encapsulated in subsieve-size agarose capsules of approximately 90 microm in diameter and implanted into preformed tumors in nude mice. Living cells were detected for >1 month after encapsulation in vitro and showed enzymatic activity (i.e., they were able to activate ifosfamide). More significant regression of preformed tumors was observed in the recipients implanted with cell-enclosing capsules compared with those implanted with empty capsules. These results suggest that the strategy of using subsieve-size agarose capsules enclosing cytochrome P450 2B1-expressing cells is feasible for tumor therapy by chemotherapeutic targeting in combination with ifosfamide administration.
Animals↗
Expression of p53 protein in esophageal squamous cell carcinoma: relation to hypoxia-inducible factor-1alpha, angiogenesis and apoptosis.
OBJECTIVES: Hypoxia-inducible factor (HIF)-1 is important in the control of transcription of several genes related to angiogenesis. We have previously reported that expression of HIF-1alpha correlates with venous invasion and clinical outcome in esophageal squamous cell carcinoma. p53 has been reported to interact with HIF-1alpha and induce ubiquitin-mediated proteosomal degradation of HIF-1alpha. The purpose of this study was to clarify whether the expression of p53 is associated with that of HIF-1alpha. METHODS: Expression of p53, HIF-1alpha and vascular endothelial growth factor (VEGF) was examined in 81 archival surgical specimens of human esophageal squamous cell carcinoma tissue. CD34 and single-stranded DNA were used to evaluate angiogenesis and apoptosis. RESULTS: Forty-seven of the 81 (58.0%) tumor specimens showed high levels of nuclear p53 immunoreactivity. Overexpression of p53 was observed in the early clinical stage of tumor development. Expression of p53 was not correlated with HIF-1alpha or VEGF expression, angiogenesis or apoptosis in esophageal carcinoma. CONCLUSIONS: These results suggest that mutations in p53 play a role in carcinogenesis but not in the progression of esophageal squamous cell carcinoma. HIF-1alpha may not only be regulated by p53 but also by other factors.
Aged↗