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Shinji Tanaka

Publications and source records attributed to Shinji Tanaka.

At least 37 records · Page 2Linked to original sources
PubMed2006

Real-time visualization and quantitation of canine gastric mucosal blood flow by contrast-enhanced ultrasonography.

OBJECTIVE: Contrast-enhanced ultrasonography has become a method of choice for evaluating gastric blood flow, but intermittent scanning techniques can sometimes distort the results. Low-mechanical index imaging using Definity as the injected contrast material has been advocated for real-time evaluation of microperfusion in other organs. We investigated the reliability of low-mechanical index imaging using Definity in the evaluation of gastric mucosal blood flow. MATERIAL AND METHODS: Under general anesthesia, 10 beagle dogs weighing 9-10 kg underwent real-time harmonic imaging under low acoustic power (mechanical index = 0.2) after intravenous contrast injection using Definity (60 mg/kg). Laser Doppler flow measurement was also performed to evaluate gastric mucosal blood flow. After administration of a diclofenac sodium suppository, low-mechanical index imaging and laser Doppler flowmetry were repeated. RESULTS: Real-time visualization of gastric mucosal blood flow was successful in all dogs undergoing low-mechanical index imaging with Definity. Quantitative assessment of gastric mucosal blood flow was successful in eight dogs. After diclofenac sodium administration, gastric mucosal blood flow measured by both laser Doppler flowmetry and contrast ultrasonography decreased in seven of eight dogs; in the other dog, gastric mucosal blood flow increased slightly. A strong positive correlation was evident between blood flow measured by laser Doppler flowmetry and low-mechanical index imaging (r=0.777, p<0.005). CONCLUSIONS: Low-mechanical index imaging with Definity is a non-invasive way to evaluate gastric mucosal blood flow in real-time, high-resolutional images, which may have additional important gastrointestinal tract applications.

Animals↗
PubMed2006

Aged garlic extract has potential suppressive effect on colorectal adenomas in humans.

Epidemiological and animal studies suggest AGE and its organosulfur constituents, such as S-allylcysteine and S-allylmercaptocysteine have anticarcinogenic effects. To confirm these effects in humans, a preliminary double-blind, randomized clinical trial using high-dose AGE (AGE 2.4 mL/d) as an active treatment and low-dose AGE (AGE 0.16 mL/d) as a control was performed on patients with colorectal adenomas-precancerous lesions of the large bowel. The study enrolled 51 patients who were diagnosed as carrying colorectal adenomas. The patients were randomly assigned to the two groups after adenomas larger than 5 mm in diameter were removed by polypectomy. The number and size of adenomas right before intake (0 mo) and at 6 and 12 mo after intake were measured using colonoscopy. Thirty-seven patients (19 in the active group, 18 in the control group) completed the study and were evaluated for the efficacy of AGE. The number of adenomas increased linearly in the control group from the beginning (the baseline), but AGE significantly suppressed both the size and number of colon adenomas in patients after 12 mo of high-dose treatment (P=0.04). The results suggest AGE suppresses progression of colorectal adenomas in humans. It appears that AGE has multiple pathways to reduce cancer incidence and suppress its growth and proliferation.

Adenoma↗
PubMed2006

The effect of Helicobacter pylori eradication therapy on gastric ulcer healing after endoscopic mucosal resection.

BACKGROUND AND AIM: It remains unclear whether Helicobacter pylori eradication therapy accelerates the healing of acute gastric ulcer after endoscopic mucosal resection (EMR) of gastric tumor. We examined the effect of H. pylori eradication therapy on ulcer healing after EMR. METHODS: Twenty-six patients who underwent successful H. pylori eradication therapy before EMR were followed prospectively. Patients underwent endoscopic examination 1 or 2 months after EMR, during which the ulcer status and reduction rate were assessed. The effect of H. pylori eradication on the quality of ulcer healing was also evaluated. Six patients in whom eradication therapy failed and 26 patients who underwent EMR without eradication therapy served as control subjects. RESULTS: Endoscopically, 18 (75%) of 24 ulcers in the eradication group were at the healing stage 1 month after EMR. The ulcer reduction rates were 85.0 +/- 2.6% and 96. 9 +/- 1.1% at 1 and 2 months after EMR, respectively. Ulcer stage and reduction rate did not differ significantly between the eradication group and control group. However, we frequently observed a better quality of ulcer healing in the eradication group than in the control groups (P < 0.01). CONCLUSION: H. pylori eradication therapy does not accelerate ulcer healing after EMR but may improve the quality of ulcer healing of gastric ulcer after EMR.

Aged↗
PubMed2006

A case of Crohn's disease with hydronephrosis caused by ureteropelvic junction obstruction.

Ureteral obstruction is a rare extraintestinal manifestation of Crohn's disease (CD). We report the case of a 20-year-old man who presented with fever, diarrhoea, and lower abdominal pain. Diagnostic studies confirmed CD and revealed an abdominal mass obstructing the right ureter and hydronephrosis. Ureteropelvic junction (UPJ) obstruction was diagnosed. Despite an elemental diet and mesalazine therapy, the hydronephrosis persisted, and the patient eventually required surgery. Successful laparoscopic pyeloplasty was performed. This is the first report of CD associated with UPJ obstruction. Ureteral obstruction as a complication of CD is discussed.

Adult↗
PubMed2006

Evaluation of endoscopic and histological findings in Helicobacter pylori-positive Japanese young adults.

BACKGROUND AND AIM: Many studies have shown that Helicobacter pylori infection is associated with chronic gastritis, peptic ulcers and gastric carcinoma in adults. However, little is known about these associations in the younger population. The aim of this study was to clarify endoscopic and histological findings in H. pylori-positive young adults. METHODS: Two hundred consecutive outpatients younger than 29 years old undergoing esophago-gastroduodenal endoscopy at four hospitals between 2001 and 2002 were eligible for this study. At endoscopy, three biopsy specimens were obtained from the mid-antrum, the angulus and the mid-corpus. Endoscopic and histological interpretations were based on the updated Sydney System. H. pylori infection was determined by histology and serology. RESULTS: The rates of H. pylori infection were 1.2% (1/86) in normal, 95.8% (46/48) in gastritis, 97.8% (45/46) in duodenal ulcers, 100% (17/17) in gastric ulcers, and 100% (3/3) in gastric carcinomas. Endoscopic findings in 112 H. pylori-positive patients were 25 normal (22.3%), 38 atrophy (33.9%), 18 erosion (16.1%), and 31 nodularity (27.7%). Histological findings of H. pylori-positive patients in the anturm revealed mononuclear cell and neutrophil infiltration in 100%, and atrophy in 27.7%. Histological findings of H. pylori-positive patients in the corpus revealed mononuclear cell infiltration in 75%, neutrophil infiltration in 60.7%, and atrophy in 28.6%. CONCLUSIONS: The study shows that H. pylori infection is strongly associated with chronic gastritis and peptic ulcers, and that histological corpus gastritis was found with high frequency in Japanese young adults.

Adult↗
PubMed2006

Surface structure of antral gastric mucosa represents the status of histologic gastritis: fundamental evidence for the evaluation of antral gastritis by magnifying endoscopy.

BACKGROUND: Recent studies have demonstrated the diagnostic potential of magnifying endoscopy in cases of histologic gastritis. The aim of the present study was to clarify whether the mucosal surface structure reflects the degree of histologic gastritis below the surface. METHODS: Gastric biopsy specimens were obtained from 1018 Japanese patients and were stained with hematoxylin and eosin. In 863 sections examined, gastritis was graded by means of the updated Sydney system, and the surface structure was classified as one of four types: flat, irregular, papillary, or non-structured. In addition, 103 patients underwent gastric examination by magnifying gastroscopy. RESULTS: The surface structure of most biopsy sections with normal mucosa and no Helicobacter pylori infection was classified as the flat type. Grades of histological gastritis were statistically lower in flat-type sections than in other types. Histologic gastritis was found in 91% of sections with a non-flat surface structure. Helicobacter pylori infection was confirmed in 96% of these cases. Most biopsy sections in patients with abnormal magnifying endoscopy features were of the non-flat type and showed histologic gastritis. CONCLUSIONS: The surface structure of the gastric mucosa reflects the status of histologic gastritis. Magnifying gastroscopy could be a useful non-invasive method of diagnosing histologic gastritis.

Female↗
PubMed2006

Receptor for advanced glycation end products is involved in impaired angiogenic response in diabetes.

Angiogenic response is impaired in diabetes. Here, we examined the involvement of receptor for advanced glycation end products (RAGE) in diabetes-related impairment of angiogenesis in vivo. Angiogenesis was determined in reconstituted basement membrane protein (matrigel) plugs containing vascular endothelial growth factor (VEGF) implanted into nondiabetic or insulin-deficient diabetic wild-type or RAGE(-/-) mice. The total, endothelial, and smooth muscle (or pericytes) cells in the matrigel were significantly decreased in diabetes, with the regulation dependent on RAGE. In the matrigel, proangiogenic VEGF expression was decreased, while antiangiogenic thrombospondin-1 was upregulated in diabetic mice, regardless of the presence of RAGE. In wild-type mice, proliferating cell nuclear antigen (PCNA)-positive cells in the matrigel were significantly less in diabetic than in nondiabetic mice, while the numbers of transferase-mediated dUTP nick-end labeling (TUNEL)-positive cells were significantly higher. This alteration in PCNA- and TUNEL-positive cells in diabetes was not observed in RAGE(-/-) mice. Similarly, the percentage of nuclear factor kappaB-activated cells is enhanced in diabetes, with the regulation dependent on the presence of RAGE. Importantly, adenovirus-mediated overexpression of endogenous secretory RAGE, a decoy receptor for RAGE, restores diabetes-associated impairment of angiogenic response in vivo. Thus, RAGE appears to be involved in impairment of angiogenesis in diabetes, and blockade of RAGE might be a potential therapeutic target.

Adenoviridae↗
PubMed2006

Deletion of the KIT gene is associated with liver metastasis and poor prognosis in patients with gastrointestinal stromal tumor in the stomach.

The goal of this study was to investigate the association of mutations in the KIT gene and the platelet-derived growth factor receptor alpha (PDGFRA) gene with clinicopathological features of patients with gastrointestinal stromal tumor (GIST) localized in the stomach. We evaluated 56 gastric GISTs for KIT and PDGFRA mutations. DNA was extracted from paraffin-embedded tumor specimens, and exons 9, 11, 13 and 17 of the KIT gene and exons 12 and 18 of the PDGFRA gene were amplified by polymerase chain reaction and sequenced. The genetic features were then compared with the clinicopathological features. Immunohistochemistry was performed for KIT, CD34, Ki-67 (as a marker of cell proliferation) and CD31 (as a marker of microvessel density), and apoptosis was assessed by in situ DNA nick-end labeling. Thirty-four (61%) of the 56 GISTs had a mutation in exon 11 of KIT, and 2 (4%) had a mutation in exon 13 of KIT. Deletions in exon 11 of KIT were the most common mutation encountered in the present study. No mutations were found in exon 9 or 17 of KIT. Six of the 20 GISTs lacking KIT mutations had a mutation in exon 18 of PDGFRA, and 1 had a mutation in exon 12 of PDGFRA. The KIT mutation-positive GISTs showed more frequent liver metastases and higher mortality than KIT mutation-negative GISTs. Our data indicate that KIT mutations, especially deletions in exon 11, are markers of poor prognosis for gastric GISTs.

Antigens, CD↗
PubMed2006

Neuropilin-1 is involved in regulation of apoptosis and migration of human colon cancer.

Vascular endothelial growth factor (VEGF) plays critical roles in cancer aggressiveness. We investigated the clinical and biological significance of neuropilin (NP)-1, a member of the VEGF receptor family, in colon carcinoma. We transfected NP-1-specific small interfering RNA (siRNA) into a human colon adenocarcinoma cell line, WiDR, and investigated its effect on proliferation, migration, and apoptosis. We also examined the relationship between clinicopathologic features and NP-1 expression in 146 patients with advanced colorectal carcinoma who had undergone surgery. Inhibition of NP-1 expression in WiDR cells by RNA interference decreased cell migration (no treatment, 143.3/field; mock, 146.8/field; scrambled siRNA, 134.6/field; NP-1 siRNA 79.6/field) and promoted apoptosis (no treatment, 3.52%; scrambled siRNA, 3.80%; NP-1 siRNA, 14.22%), but did not alter cell proliferation. In patients with advanced colorectal carcinoma, those with tumors with high levels of NP-1 staining showed a significantly higher incidence of lymph node (73.0%) or liver (86.2%) metastasis, greater microvessel density (MVD) (60.4/field), greater number of proliferating carcinoma cells (48.6%), and lesser number of apoptotic carcinoma cells (5.70 per thousand) than those with tumors with low levels of NP-1 staining (lymph node, 56.9%; liver, 59.8%; MVD, 47.8/field; proliferating cells, 42.0%; apoptosis, 8.44 per thousand). Survival for patients with tumors with high levels of NP-1 staining was significantly shorter than for those with tumors with low levels of NP-1 staining. Our results suggest that autocrine-NP-1 pathways control the migration and survival of colon carcinoma cells. NP-1 expression may stimulate tumor growth by enhanced angiogenesis and suppression of tumor cell apoptosis, which lead to metastasis and poor prognosis.

Apoptosis↗
PubMed2006

Clinicopathologic and genetic characteristics of gastric cancer in young male and female patients.

The pathways of gastric cancer in young patients (40 years of age or younger) have not yet been determined. We therefore examined clinicopathologically and genetically 68 gastric cancers in young patients and 66 tumors in older patients (41 years of age or older). Mutations in B-raf and K-ras were identified by PCR-SSCP following sequencing. Microsatellite instability (MSI) and hMLH3 mutations were also examined. Histopathologically, diffuse-type gastric cancer and cancer in the whole of the stomach were found significantly more often in young patients than in older patients (21% vs. 2%, P = 0.0006, and 77% vs. 32%, P < 0.0001, respectively). Genetically, MSI and hMLH3 mutations were found significantly more often in tumors in young patients than in tumors in older patients (15% vs. 4%, P = 0.040, and 9% vs. 0%, P = 0.036, respectively). Tumors in young female patients were found significantly less often in the lower-third of the stomach and showed a significantly greater frequency of MSI, compared to tumors in young male patients (33% vs. 9%, P = 0.046, 5% vs. 30%, P = 0.010, respectively). These results suggest that the pathways of gastric carcinogenesis differ between young patients and older patients, and that the pathways differ between the sexes in young patients.

Adult↗
PubMed2006

Genetic progression and divergence in superficial esophageal squamous cell carcinoma by loss of heterozygosity analysis.

Esophageal squamous cell carcinoma (SCC) is one of the most common fatal carcinomas worldwide and has some of the most malignant characteristics among gastrointestinal tumors. Although a high frequency of loss of heterozygosity (LOH) for various genes has been observed in esophageal SCCs, these findings do not provide any information regarding the genetic pathways that may underlie the development and progression of this type of tumor. To clarify the temporal and topographic pathways in the genetic evolution of esophageal SCC, we microdissected multiple foci from superficial mucosal invasive foci of tumors. We then carried out LOH analyses of the microdissected neoplastic foci. Sixteen superficial esophageal SCCs were examined. Three to six carcinoma foci from each superficial esophageal SCC were individually microdissected. We used 12 oligonucleotide primer pairs specific for the microsatellite markers for which frequent LOH in esophageal SCC has been reported. All tumors exhibited LOH of at least three microsatellite loci. A frequent homogeneous LOH pattern was detected for TP53 (60%), D16S518 (43%) and D3S1234 (29%), suggesting that the loss of these alleles is an early event in the development of esophageal SCC. A heterogeneous LOH pattern was detected for D13S325 (87%), D10S559 (73%), D3S1568 (58%), D3S1234 (57%) and D3S1621 (56%), suggesting that the loss of these alleles is a late event in the development of esophageal SCC. All tumors showed the LOH pattern of single clonal neoplasms with genetic progression and divergence. In conclusion, by extensive sampling of SCC lesions with microdissection and LOH analysis of multiple chromosomal loci, we successfully demonstrated dynamic and successive accumulation of genetic alterations in early SCC.

Aged↗
PubMed2006

Genetic and pathologic characteristics of gastrointestinal stromal tumors in extragastric lesions.

The goal of this study was to investigate differences in the clinicopathologic and genetic characteristics of gastric and extragastric gastrointestinal stromal tumors (GISTs). We evaluated 13 extragastric GISTs and compared them with 56 gastric GISTs, which were described previously. DNA was extracted from paraffin-embedded tumor specimens, and exons 9, 11, 13, and 17 of the KIT gene and exons 12 and 18 of the platelet-derived growth factor receptor alpha (PDGFRA) gene were amplified by polymerase chain reaction and sequenced. Immunohistochemistry was performed for KIT, CD34, Ki-67 (as a marker of cell proliferation), and CD31 (as a marker of microvessel density), and apoptosis was assessed by in situ DNA nick end-labeling. Of the 13 extragastric GISTs 7 (54%) had a mutation in exon 11 of KIT, and 2 (15%) had a mutation in exon 13 of KIT. Deletions in exon 11 of KIT were the most common mutation encountered in the extragastric GISTs. The extragastric GISTs, especially small intestinal GISTs, showed larger deletions, leading to deletions of amino acid residues in the KIT protein, and higher vascularity than did the gastric GISTs. These data suggest that extragastric GISTs differ from gastric GISTs with respect to associated mutations and angiogenic activity.

Adult↗
PubMed2005

Monocyte chemoattractant protein-1 transfection induces angiogenesis and tumorigenesis of gastric carcinoma in nude mice via macrophage recruitment.

PURPOSE: Monocyte chemoattractant protein-1 (MCP-1) is a chemokine that has various roles in tumor development and progression. We previously reported that expression of MCP-1 is associated with macrophage infiltration and tumor vessel density in human gastric carcinomas. The present study was undertaken to obtain direct evidence that MCP-1 participates in recruitment of macrophages and induction of angiogenesis. EXPERIMENTAL DESIGN: We did transfection experiments to analyze the role of MCP-1 in tumorigenicity and angiogenesis in gastric carcinoma in nude mice. The human MCP-1 gene cloned into the BCMGS-Neo expression vector was transfected into the human gastric carcinoma TMK-1 cell line. We examined tumor volumes with the ectopic s.c. xenograft model and tumorigenicity with the orthotopic gastric xenograft model. We determined intratumor microvessel counts and tumor-infiltrating macrophage counts by immunohistochemical staining. RESULTS: There was no difference in in vitro proliferation between MCP-1-transfected TMK-1 cells and mock-transfected (control) cells; however, MCP-1 transfectants induced tumor growth in ectopic xenografts and increased tumorigenicity and induced lymph node metastases and ascites in orthotopic xenografts. In both ectopic and orthotopic xenograft models, strong infiltration of macrophages was observed within and around the tumors after implantation of MCP-1 transfectants whereas fewer macrophages were seen after inoculation of control cells. The microvessel density was significantly higher in tumors produced by MCP-1 transfectants than in control tumors. CONCLUSIONS: MCP-1 produced by gastric carcinoma cells may regulate angiogenesis via macrophage recruitment. MCP-1 may be a potential target for antiangiogenic therapy for gastric carcinoma.

Animals↗