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Biomedical subjects

Fumio Shimamoto

Publications and source records attributed to Fumio Shimamoto.

At least 19 recordsLinked to original sources
PubMed2007

Lymphatic vessel density at the site of deepest penetration as a predictor of lymph node metastasis in submucosal colorectal cancer.

PURPOSE: Lymph node metastasis is an important factor that influences curability after endoscopic treatment of submucosal colorectal cancer. This study was designed to determine the usefulness of identification of lymphatic vessels by immunohistochemistry in predicting lymph node metastasis of submucosal colorectal cancer. METHODS: Lymphatic involvement was assessed by hematoxylin and eosin staining and podoplanin immunostaining on samples resected from 268 patients with submucosal colorectal cancer. Lymphatic vessel density was estimated by two investigators by average count of three fields (x200) in the area of greatest number of podoplanin-positive capillaries at the site of deepest submucosal penetration. Relations with other clinicopathologic parameters also were investigated. RESULTS: Lesions with high lymphatic vessel density (> or =9 vessels per field) showed a significantly greater incidence of lymph node metastasis than did those with low lymphatic vessel density (<9 vessels per field; 23.3 vs. 8.4 percent). By multivariate analysis, lymphatic vessel density was determined to be an independent risk factor for lymph node metastasis of submucosal colorectal cancer (P = 0.0044). Lymphatic vessel density also correlated with tumor budding and the degree of inflammation at the invasive front. CONCLUSIONS: Identification of lymphatic vessels by podoplanin immunostaining provides objective and accurate evaluation of lymphatic involvement. Lymphatic vessel density at the site of deepest penetration is a useful predictor of lymph node metastasis of submucosal colorectal cancer.

Colorectal Neoplasms↗
PubMed2005

Protective effects of a water-soluble extract from cultured medium of Ganoderma lucidum (Rei-shi) mycelia and Agaricus blazei murill against X-irradiation in B6C3F1 mice: Increased small intestinal crypt survival and prolongation of average time to animal death.

Radioprotective effects of a water-soluble extracts from cultured medium of Ganoderma lucidum (Rei-shi) mycelia (designed as MAK) and Agaricus blazei (Agaricus) against the shortening of survival time or the injury of crypt by X-irradiation were investigated in male B6C3F1 mice. MAK and Agaricus at three different doses were mixed into basal diet into biscuits at 5, 2.5 and 1.25% and administered from 1 week before irradiation. MAK (5% group) significantly prolonged animal survival as compared with basal diet group (control group) after 7 Gy of X-ray irradiation at a dose rate of 2 Gy min(-1). At doses of 8, 10 and 12 Gy X-irradiation at a dose rate of 4 Gy min(-1) MAK (5% group) significantly increased crypt survival as compared to other groups. These results suggest that MAK can act as a radioprotective agent.

Agaricus↗
PubMed2005

Decrease in size of azoxymethane induced colon carcinoma in F344 rats by 180-day fermented miso.

The present study was designed to investigate the effects of fermented miso (fermented soybean paste) on the induction of colon tumors by azoxymethane (AOM) in male F344 rats. A total of 91 rats, 6 weeks of age, were divided into 5 groups and given weekly subcutaneous injections of AOM (15 mg/kg body wt) for 3 weeks. The animals were placed on diets one week before the first AOM dose: commercial normal control MF diet or a diet containing 10% 2-year, 180-day fermented, or 3-4-day fermented miso. There were no differences in body and organ weights, and no aberrant crypt foci (ACF) among carcinogen-treated groups at week 25. The rates of tumor incidence were 45%, 85%, 75% and 60% with the 2-year, 180-day, and 3-4-day fermented miso and MF, respectively, and those for colon tumors were 34%, 55%, 60% and 55%, respectively. The size of well-differentiated adenocarcinomas and total (well differentiated and signet ring cell) adenocarcinomas in the 180-day fermented miso group was significantly smaller than that in the 2-year fermented miso and MF+AOM groups. Nuclear staining of beta-catenin in colon tumors was increased for the 3-4-day fermented miso compared to the 180-day fermented miso. Cdx2 staining tendency was decreased in colon tumors and adenocarcinomas compared to normal mucosa and ACF, which stained in 100% of cases. In addition, the PCNA index was significantly reduced in the 180-day group compared with those groups receiving the 3-4-day fermented miso and MF diet. The germinal region was also decreased. The present results indicate that dietary supplementation with 180-day fermented dietary miso could act as a chemopreventive agent for colon carcinogenesis.

Animals↗
PubMed2004

Magnifying colonoscopic features of ulcerative colitis reflect histologic inflammation.

BACKGROUND: Colonoscopy plays an important role in the diagnosis of ulcerative colitis and the determination of disease activity. Standard colonoscopic findings, however, do not often agree with histologic findings. The aim of this study was to clarify the relation between magnifying colonoscopic features and histologic inflammation in the course of ulcerative colitis. METHODS: We performed magnifying colonoscopy examinations in 60 patients with ulcerative colitis. We classified the features into six types and analyzed the relations among these features, standard colonoscopic features (Matts grades), and pathohistological findings. RESULTS: It was difficult to distinguish the remission stage from the active stage by standard colonoscopy in cases of Matts grade 2 disease. There was a relation, however, between the magnifying colonoscopic types and the degrees of histologic inflammation. The magnifying colonoscopic types reflected histologic inflammation status more accurately than did standard colonoscopic findings. CONCLUSION: Magnifying colonoscopy is useful for determining the degree of histologic change without biopsy in patients with ulcerative colitis.

Adult↗
PubMed2004

Expression and localization of MUC1, MUC2, MUC5AC and small intestinal mucin antigen in pancreatic tumors.

Alterations in the expression of mucin family members play an important role as well as alterations in oncogenes and onco-suppressor genes in carcinogenesis and progression of pancreatic cancer. We analyzed the expression and localization of MUC1, MUC2, MUC5AC and small intestinal mucin antigen (SIMA) in pancreatic tumors. MUC1 expression was observed in almost all samples, whereas MUC2 expression was not. MUC5AC expression was observed in 73.9% of the cancerous regions, 48.7% of the dysplastic regions and 72.0% of the hyperplastic regions but not in the normal pancreatic duct. SIMA expression was observed in 45.7% of cancerous regions, 17.9% of the dysplastic regions and 8.0% of the hyperplastic regions. Furthermore, stromal expression of MUC1, MUC5AC and SIMA was observed in 37.0%, 60.9% and 26.1% of the cancerous regions, respectively. Stromal expression of these mucins was not observed in the hyperplastic regions and normal pancreatic duct and was observed in only two dysplastic regions. The survival of pancreatic cancer patients with stromal expression of MUC1 or SIMA was worse than that of other patients (P=0.04). In conclusion, the localization of mucin expression, especially stromal expression of MUC1 or SIMA, might be a prognostic factor for patients with pancreatic cancer.

Adult↗
PubMed2003

Regulation of T helper type-1 immunity in hapten-induced colitis by host pretreatment with granulocyte colony-stimulating factor.

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is an immunoregulatory drug whose effects include modulation of antigen-presentation. We investigated the potential ameliorative effect of pretreatment with rhG-CSF in a hapten-induced colitis animal model. Sprague-Dawley rats were given rhG-CSF (125 microg/kg subcutaneously twice a day for 5 days) before a colonic instillation of 2,4,6-trinitrobenzene sulfonic acid (TNBS) in 50% ethanol. Consequent colonic damage was evaluated pathologically, and cytokine mRNA expression levels in macroscopically inflamed sites were measured by real-time quantitative reverse transcription-polymerase chain reaction. Pretreatment with rhG-CSF remarkably attenuated both the loss of body weight and colonic wall thickening due to progressive transmural inflammation. In the control, treatment with TNBS led to a statistically significant (p < 0.05) upregulation of IFN-gamma mRNA expression in the inflammatory sites measured at post-treatment day 7. In the experimental group, pretreatment with rhG-CSF abrogated transcription of IFN-gamma (p < 0.05), but was not, however, associated with an upregulation of IL-4 or the regulatory cytokines TGF-beta and IL-10. Furthermore, transcription of IL-12p35 (a rate-limiting factor for the production of IL-12) was significantly (p < 0.05) downregulated by rhG-CSF at 24h post-TNBS instillation, whereas IL-12p40 was not affected. Pretreatment with rhG-CSF drastically attenuated the degree of TNBS-induced colitis through selective downregulation of Th1-associated cytokines.

Adjuvants, Immunologic↗
PubMed2003

p53 expression, K-ras gene mutation and microsatellite instability in gastric B-cell lymphomas.

BACKGROUND AND AIMS: Genetic mechanisms involved in the development of gastric B-cell lymphomas remain unclear. The aim of the present study was to clarify the roles of mutations of the p53 and K-ras genes, and microsatellite instability (MSI) in the development of gastric B-cell lymphomas. METHODS: We investigated p53 immunoreactivity, mutations of the K-ras gene, and MSI in 27 gastric marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue type (MZBCL) and 24 diffuse large B-cell lymphomas (DLBCL). p53 immunoreactivity was examined using a monoclonal antibody, DO-7. Mutation of the K-ras gene was detected by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis. MSI was examined at five microsatellite loci with a microsatellite assay. Cases were classified as having high-frequency MSI (MSI-H) (>/= 2 loci showing instability), low-frequency MSI (MSI-L) (only one locus showing instability), or as microsatellite stable. RESULTS: p53 immunoreactivity was detected in 1 of 16 (6%) MZBCL and 8 of 19 (42%) DLBCL. Frequency of p53 immunoreactivity in DLBCL was significantly higher than that in MZBCL (P = 0.018). MSI-H was detected only in 1 of 20 (5%) DLBCL. None of the cases examined showed mutation of the K-ras gene. CONCLUSIONS: These data suggest that mutations of the p53 gene may play an important role in the development of gastric DLBCL, and that mutations of the K-ras gene and MSI may be involved in little part of the development of gastric B-cell lymphomas.

Chromosomal Instability↗
PubMed2003

Prevalence of Helicobacter pylori resistance to clarithromycin and metronidazole determined by 23S ribosomal RNA and rdxA gene analyses in Hiroshima, Japan.

BACKGROUND AND AIMS: Resistance to antibiotics in Helicobacter pylori is increasing and becoming a serious problem in eradication treatment of H. pylori. The prevalence of H. pylori infections that are resistant to clarithromycin, metronidazole, or both were determined in H. pylori isolates in Hiroshima, Japan. METHODS: Sixty Japanese patients with H. pylori infection were collected between 1999 and 2000. To detect the resistance to clarithromycin and metronidazole, mutations of the 23S ribosomal RNA (rRNA) and rdxA genes that are responsible for resistance in H. pylori, were examined by direct sequencing analysis. RESULTS: Resistance to clarithromycin and metronidazole was detected in 12 (20.0%) and nine (15.0%) of the patients, respectively. Dual resistance to clarithromycin and metronidazole was detected in five (8.3%) patients. CONCLUSION: These results indicate that the relatively high prevalence of the dual resistance in H. pylori isolates may need special attention and new therapeutic approaches in Japan.

Anti-Bacterial Agents↗
PubMed2003

Small rectal carcinoid with lymph node metastasis diagnosed prior to treatment.

We treated a 59-year-old man with a small, yellowish, submucosal rectal tumour that was detected incidentally during a colonoscopic examination. Endoscopic ultrasonography revealed a hypoechoic submucosal tumour 13 mm in diameter. Computed tomography and magnetic resonance imaging studies were performed, and pararectal and para-obturator lymph node involvement was confirmed. The patient underwent Miles' operation with lymph node dissection; 24 months later, he is disease free. We were able to diagnose rectal carcinoid tumour and evaluate the lymph node metastasis prior to surgery. Even with a small carcinoid, it is important to determine the depth of invasion and the presence of lymph node metastasis prior to treatment.

Carcinoid Tumor↗
PubMed2003

Somatic mutation of mitochondrial DNA in Helicobacter pylori-associated chronic gastritis in patients with and without gastric cancer.

Somatic mutations of the mitochondrial DNA (mtDNA) are associated with development of various types of human cancer. To elucidate the significance of somatic mutations of the mtDNA in gastric carcinogenesis, we examined mtDNA mutations in gastric cancers and in Helicobacter pylori-associated chronic gastritis (H. pylori-CG), which is associated with an increased risk for gastric cancer development. Specimens of gastric cancer and gastric mucosa were obtained from 73 gastric cancer patients with H. pylori-CG, 75 cancer-free H. pylori-CG patients and 30 H. pylori-negative healthy subjects. Mutations of a specific mononucleotide repeat (D310) of the mtDNA were examined by microsatellite assay. mtDNA mutations were detected in 9 of 56 (16%) gastric cancers, in 10 of 148 (7%) H. pylori-CG and none of the 30 H. pylori-negative healthy subjects. mtDNA mutations in H. pylori-CG were significantly more frequent in gastric cancer patients than in cancer-free patients (12% vs. 1%, p=0.008). In addition, mtDNA mutations in H. pylori-CG were significantly more frequent in patients with mtDNA mutated gastric cancer than in patients with mtDNA unmutated gastric cancer (66% vs. 4%, p<0.001). These data suggest that somatic mutations of the mtDNA may be involved in the early stages of gastric carcinogenesis.

Chronic Disease↗
PubMed2002

p53 Codon 72 polymorphism in gastric cancer susceptibility in patients with Helicobacter pylori-associated chronic gastritis.

p53 codon 72, which produces variant proteins with an arginine (Arg) or proline (Pro), has been reported to be associated with cancers of the lung, esophagus and cervix. However, there have been no reports on the p53 codon 72 polymorphism in gastric cancer susceptibility in patients with Helicobacter pylori-associated chronic gastritis (H. pylori-CG). We, therefore, examined the polymorphism in 117 gastric cancer patients (72 intestinal type and 45 diffuse type) with H. pylori-CG and 116 H. pylori-CG patients without gastric cancer as controls. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was performed to analyze the p53 codon 72 polymorphism. The crude genotypic frequencies in the gastric cancer patients were similar to those of the controls. However, when gastric cancers were classified by histologic subtype, the Pro/Pro was more frequent in the patients with diffuse type gastric cancer than in the controls (22.2% of cases vs. 12.1% of controls). The Pro/Pro genotype was associated with a 2.98-fold higher risk of diffuse-type cancer compared to the Arg/Arg genotype (95% confidence interval [CI] 1.07-8.32, p = 0.038). These results suggest that the Pro/Pro genotype at p53 codon 72 contributes to susceptibility for diffuse-type gastric cancer in patients with H. pylori-CG. The p53 codon 72 polymorphism may serve as the genetic marker for the risk assessment of the diffuse-type gastric cancer development in patients with H. pylori-CG.

Adult↗
PubMed2002

K-ras mutation in helicobacter pylori-associated chronic gastritis in patients with and without gastric cancer.

Mutations of an oncogene, K-ras, are associated with the development and progression of many types of human cancer. To elucidate the significance of K-ras mutations in gastric carcinogenesis, we examined K-ras mutations in gastric cancers and in Helicobacter pylori-associated chronic gastritis (H. pylori-CG), which is associated with an increased risk for the gastric cancer development. Specimens of gastric cancer and H. pylori-CG were obtained from 64 gastric cancer patients with H. pylori-CG, 99 cancer-free H. pylori-CG patients and 30 H. pylori-negative healthy subjects. K-ras mutations were examined by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP), followed by DNA sequencing analysis. K-ras mutations were detected in 4 of 48 (8.3%) gastric cancers, in 10 of 163 (6.1%) H. pylori-CG and none of the 30 H. pylori-negative healthy subjects. In the gastric cancer patients, mutated K-ras was detected in differentiated type cancers but not in any of the undifferentiated type cancers. K-ras mutations in H. pylori-CG were significantly more frequent in gastric cancer patients than in cancer-free patients (10.9% vs. 3.0%, p = 0.044). In addition, K-ras mutations in H. pylori-CG were significantly more frequent in patients with K-ras mutated gastric cancer than in patients with K-ras unmutated gastric cancer (50.0% vs. 3.7%, p = 0.037). These data suggest that the genetic mechanism(s) of carcinogenesis differs between the differentiated type and the undifferentiated type of gastric cancer and that K-ras mutations may be involved in the early stages of gastric carcinogenesis of the differentiated type.

Biopsy↗
PubMed2002

High incidence of B-cell monoclonality in follicular gastritis: a possible association between follicular gastritis and MALT lymphoma.

Many studies have indicated a close association between gastric mucosa-associated lymphoid tissue (MALT) lymphoma and Helicobacter pylori ( Hp) infection. Follicular gastritis (FG), a rare type of gastritis, is also closely associated with Hp infection and histologically similar to MALT lymphoma. However, there are few studies investigating the relationship between FG and MALT lymphoma. To clarify the issue, we examined the B-cell monoclonality in FG by immunoglobulin heavy chain (IgH) gene rearrangement. Seventy FG patients (all Hp-positive, 23 males and 47 females, median age 33 yr) were investigated; 70 age-and gender-matched non-FG Hp-positive controls and 24 non-FG Hp-negative controls were also examined. Two gastric biopsies, one from the antrum and one from the corpus, were obtained from each patient. DNA was extracted from formalin-fixed, paraffin-embedded biopsy specimens. IgH gene rearrangement was examined by semi-nested polymerase chain reaction (PCR). In the antral mucosa, monoclonal B-cell populations were detected in 19 (32%) of 60 FG, in 6 (10%) of 60 Hp-positive controls, and in none of 20 Hp-negative controls. In the corporal mucosa, monoclonal B-cell populations were detected in 14 (30%) of 47 FG, in 6 (11%) of 54 Hp-positive controls, and in none of 20 Hp-negative controls. The incidence of monoclonal B-cell populations in the FG patients was higher than in both Hp-positive and Hp-negative controls ( P<0.05). The monoclonal B-cell populations disappeared after successful Hp eradication in 8 of 8 FG patients examined. These data suggest that FG may be strongly associated with MALT lymphoma, and that Hp eradication therapy may be indicated in FG.

Adolescent↗
PubMed2002

Clinical significance of vascular endothelial growth factor C expression and angiogenesis at the deepest invasive site of advanced colorectal carcinoma.

AIM: Vascular endothelial growth factor C (VEGF-C) is known to be associated with the development of the lymphatic vascular system. The aim of this study was to elucidate the clinical significance of VEGF-C expression and microvessel density (MVD) at the deepest invasive site in advanced colorectal carcinoma (CRC). METHODS: 152 patients who had undergone surgical resection for advanced CRC entered this study. VEGF-C expression was examined immunohistochemically with anti-VEGF-C polyclonal antibody C-20. Tumor MVD was determined immunohistochemically with anti-CD34 antibody. VEGF-C expression was defined as positive if distinct staining of the cytoplasm was observed in at least 10% of tumor cells at the deepest invasive site, central portion and superficial part of the tumor. MVD was estimated by averaging the count of three x400 fields in the most vascular area at the deepest invasive site. RESULTS: VEGF-C expression was detected in 71 of 152 lesions (46.7%) at the deepest invasive site. VEGF-C expression correlated significantly with poorer histologic grade, depth of invasion, lymphatic invasion, lymph node metastasis, venous invasion, liver metastasis and Duke's stage. At the central portion and superficial part, there were no significant differences between VEGF-C expression and clinicopathological findings. VEGF-C expression at the deepest invasive site also correlated significantly with MVD. In cases with curative surgery, patients with VEGF-C expression at the deepest invasive site had a significantly poorer prognosis than those without VEGF-C expression. Furthermore, prognosis for patients with both VEGF-C expression and high MVD at the deepest invasive site was significantly poorer than that of patients without VEGF-C expression and with low MVD. Multivariate analysis with logistic regression for 5-year survival in patients with curative surgery showed that lymph node metastasis and VEGF-C expression were significant risk factors. CONCLUSION: VEGF-C expression at the deepest site of tumor invasion can be a useful predictor of poor prognosis in advanced CRC and show a close relation to angiogenesis.

Aged↗
PubMed2002

Variable E-cadherin expression in a MNU-induced colon tumor model in rats which exposed with 50 Hz frequency sinusoidal magnetic field.

Inactivation of the E-cadherin system by multiple mechanisms, including both genetic and epigenetic events, plays a significant role in multistage carcinogenesis. We have investigated the effects of sinusoidal electromagnetic fields (SMF) on E-cadherin expression in an MNU (N-methyl-N-nitrosurea)-induced colon tumor model. Male wistar albino rats were used for the study. The rats were classified into four groups: I (MNU), II (SMF+MNU), III (SMF) and IV (control). After administered at MNU in 1st and 2nd groups, 2nd and 3rd groups were exposed to a sinusoidal magnetic field (SMF, 50 Hz, 5 mT) for 6 hours/day for 8 months. The expression of E-cadherin were examined in four groups of rat colon tissues by immunohistochemistry on paraffin sections. For immunohistochemical analysis, the labeled streptavidin biotin method was performed using a Vectastain Universal Quick Kit with microwave accentuation. Fisher's exact test was used for statistical analysis between proportions. Immunohistochemical studies of E-cadherin expression in this model demonstrated significant differences for cytoplasmic expression pattern. These results suggest that the electromagnetic fields result in significant alterations in cell adhesion mechanisms. This study has implications for understanding the role of fields in cell detachment in cancer metastasis. Further work is required to determine the relative effect of the magnetic fields on these phenomena.

Animals↗