Biomedical subjects

Yutaka Shimada

Publications and source records attributed to Yutaka Shimada.

105 records · Page 6Linked to original sources

PubMed2002

Novel targets for the 18p11.3 amplification frequently observed in esophageal squamous cell carcinomas.

Amplification of DNA in certain chromosomal regions, with consequent over-expression of specific genes within these amplicons, plays a crucial role in the development and progression of human cancer. Since our previous comparative genomic hybridization (CGH) study revealed frequent amplifications at 18p in esophageal squamous cell carcinomas (ESC) cell lines, we focused on the identification of genetic target(s) within the 18p amplicon. In four cell lines having remarkable copy-number amplification with homogeneously staining region (HSR) pattern by fluorescence in situ hybridization (FISH), the smallest common region of overlapping covered approximately 3.5 Mb at 18p11.3. We screened 29 ESC cell lines to discern amplifications and expression levels of 14 known genes and 21 uncharacterized transcripts within the amplicon. Only four known genes, YES1, TYMS, HEC and TGIF showed amplification and consequent over-expression. These genes were amplified in several of primary ESCs. Moreover, resistance to transforming growth factor beta (TGFbeta)-induced growth inhibition was enhanced in four cell lines with amplification and expression of TGIF, which encodes the repressor for TGFbeta-activated transcription, appears to be involved in the progression of ESC. Taken together, these results suggest that YES1, TYMS, HEC and TGIF are likely to be candidate targets for 18p11.3 amplification and be associated with esophageal tumorigenesis.

Carcinoma, Squamous Cell↗

PubMed2002

Suppression of N-nitrosomethylbenzylamine (NMBA)-induced esophageal tumorigenesis in F344 rats by resveratrol.

Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a natural product occurring in grapes and various other plants with medicinal properties associated with reduced cardiovascular disease and reduced cancer risk. To evaluate the possibility and potential mechanism(s) of which resveratrol inhibits N-nitrosomethylbenzylamine (NMBA)-induced rat esophageal tumorigenesis, 96 F344 male rats were divided into 10 groups and resveratrol (1 and 2 mg/kg) was administered orally or intraperitoneally (i.p.). In the groups in which resveratrol was administered at 2 mg/kg (orally, for 16 weeks), 1 and 2 mg/kg (i.p., for 16 weeks) and 1 mg/kg (i.p., for 20 weeks), the number of NMBA-induced esophageal tumors per rat was significantly reduced to 78, 62, 54 and 48, respectively (P < 0.05), and the size of maximum tumors in each group with resveratrol treatment was also significantly smaller than that in NMBA alone group (P < 0.05). Although the pathological examination did not indicate significantly decreased incidence of carcinomas by administering resveratrol, the tendency of carcinogensis suppression was observed (P = 0.177). Semi-quantitative RT-PCR and ELISA analysis demonstrated that following NMBA treatment, the expression of COX-1 mRNA was strongly present in tumor tissues, while weakly present in non-tissues; the expression of COX-2 mRNA was induced in both tumor and non-tumor tissues. The production of prostaglandin E(2) (PGE(2)) increased approximately 6-fold, compared with the normal esophageal mucosa. The higher expression of COX-1, the up-regulated COX-2 expression and the increased levels of PGE(2) synthesis were all significantly decreased by administering resveratrol. Our study suggests that resveratrol suppressed NMBA-induced rat esophageal tumorigenesis by targeting COXs and PGE(2), and therefore may be a promising natural anti-carcinogenesis agent for the prevention and treatment of human esophageal cancer.

Animals↗

PubMed2002

Endoscopic versus conventional open thyroid lobectomy for benign thyroid nodules: a prospective study.

The current study compared results between endoscopic thyroidectomy and conventional surgery in a prospective study. Twenty-two patients eligible for endoscopic thyroidectomy were evaluated. Patients were divided into group A, for conventional open thyroidectomy (n = 12), and group B, for endoscopic thyroidectomy (n = 10). Operative time, blood loss, postoperative complications and analgesic requirements, and time taken to return to normal activity were compared. Groups A and B were statistically balanced. Blood loss was significantly less in group B than in group A (11 versus 32 mL; P = 0.004), but no significant differences were observed in any of the other parameters. No postoperative complications (hemorrhage or recurrent laryngeal nerve paralysis) were present in either group. Compared with conventional surgery, endoscopic thyroidectomy for benign thyroid nodules was associated with less blood loss, although blood loss was minimal for both procedures. There were no practical differences in technical ability to perform.

Adult↗

PubMed2002

The efficacy of herbal medicine (kampo) in reducing the adverse effects of IFN-beta in chronic hepatitis C.

The purpose of this study was to determine if the adverse effects of interferon (IFN) in hepatitis C patients could be reduced by treatment with Japanese Oriental (Kampo) medicine. Twelve patients with chronic hepatitis C were treated with a combination of IFN-beta and either Mao-to or Dai-seiryu-to (groups A and B), and 16 patients were treated with IFN-beta alone (group C). Mao-to was administered to eight patients and Dai-seiryu-to was administered to four in groups A and B, respectively. Adverse effects were evaluated by clinical and laboratory examinations. The severity of symptoms was daily self-classified into four categories (1: none, 2: very slight, 3: moderate, and 4: serious), using a questionnaire consisting of 29 items. Scores of symptom such as discomfort and fever in group A, and discomfort, general malaise, paresthesia and arthralgia in group B were significantly lower than those in group C (p < 0.05). In all patients, HCV-RNA was negative at the end of the treatment, and serum alanine aminotransferase (ALT) levels had normalized transiently in all group A and B patients with genotype 1b by 2 weeks after cessation of IFN treatment. This study indicates that Kampo medicines are useful for reducing the adverse effects accompanying IFN treatment in patients with chronic hepatitis C without reducing the antiviral effects.

Adult↗

PubMed2002

Expression of cyclooxygenase-2 is associated with carcinogenesis of the lower part of thoracic esophageal squamous cell carcinoma and p53 expression.

Cyclooxygenase (COX) is a key enzyme in arachidonic acid metabolism. Two isoforms of this enzyme have been identified: constitutive COX-1 and inducible COX-2. Recently, expression of COX-2 has been found in several human carcinomas. COX-2 expression may contribute to the synthesis of prostanoids, which relate to carcinogenesis and tumor progression. We investigated the expression of COX-2 in 175 human esophageal squamous cell carcinoma tissues using immunohistochemistry and evaluated the relationship with clinicopathological findings. In addition, due to the known relevance of p53 to carcinogenesis, we evaluated the expression of COX-2 and p53. Interestingly, cancer tissues with high COX-2 expression were found significantly more often in the middle and lower esophagus than in the cervical and upper esophagus (p = 0.0014). No significant differences were observed in other clinicopathological data such as age, sex, histopathological grading, lymphatic invasion, venous invasion, TNM clinical classification and patient prognosis. p53 expression was associated with the expression of COX-2 (p = 0.0122). Our findings suggest that COX-2 may play a role in the development of squamous cell carcinoma in the lower part of the thoracic esophagus.

Adult↗

PubMed2002

Clinicopathological significance of human macrophage metalloelastase expression in esophageal squamous cell carcinoma.

OBJECTIVE: Human macrophage metalloelastase is referred to as matrix metalloproteinase (MMP-12), its function in tumors is contradictory. The current study was undertaken to investigate the role of MMP-12 in esophageal squamous cell carcinoma (SCC). PATIENTS AND METHODS: We analyzed the levels of MMP-12 mRNA expression in 67 patients with primary esophageal SCC by Northern blot analysis and the tissues were subjected to in situ hybridization analysis for MMP-12. Immunohistochemical staining was performed to detect the macrophages infiltrated in esophageal SCCs. RESULTS: MMP-12 mRNA was detected in 27 of 67 esophageal SCC samples by Northern blot analysis. In situ hybridization and immunohistochemical staining revealed that MMP-12 mRNA signals are located mainly in tumor cells. The frequency of lymph node metastasis was significantly higher in the MMP-12-positive (MMP-12(+)) subgroup than MMP-12-negative (MMP-12(-)) subgroup (p < 0.05); furthermore, invasion was significantly deeper in the MMP- 12(+) subgroup than in the MMP-12(-) subgroup (p < 0.01). MMP-12 mRNA was inversely correlated with prognosis (p < 0.05). However, Cox multivariate analysis revealed that upregulation of MMP-12 was not related to prognosis. CONCLUSIONS: MMP-12 gene expression was associated with the progression of esophageal SCC; however, it was not an independent prognostic factor.

Aged↗

PubMed2002

Herbal medicine and false-positive results on lymphocyte transformation test.

In vitro mitogenic activity of 16 herbs and 3 Kampo (herbal medicine) formulae have been reported in experimental studies. It is not known how many herbs and Kampo formulae in total have mitogenic activity. Lymphocyte transformation test (LTT) is generally utilized to diagnose drug-induced liver injury. In LTT, mitogenic activity is assessed by measuring 3H-thymidine incorporation. The objective of the present study was to determine which herbs and which Kampo formulae caused false-positivity on LTT. We examined 2496 summaries of all admission records from 1979 to 1999 in our department. We selected patients in whom liver injuries were diagnosed as definitely unrelated to Kampo medication. In these patients, LTT was performed for some herbs contained in the suspect Kampo medicines, resulting in positive LTT for 17 herbs: Evodiae Fructus (Goshuyu), Zizyphi Fructus (Taiso), Ginseng Radix (Ninjin), Zingiberis Rhizoma (Shokyo), Hoelen (Bukuryo), Aconiti Tuber (Bushi), Angelicae Radix (Toki), Cnidii Rhizoma (Senkyu), Rehmanniae Radix (Jio), Ephedrae Herba (Mao), Anemarrhenae Rhizoma (Chimo), Cinnamomi Cortex (Keihi), Bupleuri Radix (Saiko), Artemisiae Capillari Spica (Inchinko), Persicae Semen (Tonin), Moutan Cortex (Botanpi) and Paeoniae Radix (Shakuyaku). These results were considered false-positive, because the results were observed in the "definitely unrelated" patients. Mitogenic activity inherent to some herbs and Kampo formulae may sometimes cause false-positivity on LTT in clinical situations. These examples suggest that LTT for Kampo formulae may be unreliable as a diagnostic method for drug-induced liver injury.

Chemical and Drug Induced Liver Injury↗

PubMed2002

Rhubarb use in patients treated with Kampo medicines--a risk for gastric cancer?

In vitro mutagenic effects have been reported for ingredients contained in rhubarb. Therefore, rhubarb (Rhei Rhizoma) as an anthranoid laxative could be associated with a risk of developing gastric cancer as well as colorectal cancer. We are not aware of any reports that have examined the relationship between the use of rhubarb and the development of gastric cancer. During the period between 1979 and 1999, we treated 14,616 patients using various Kampo medicines, which sometimes contained rhubarb. In the present study, we determined whether patients, diagnosed with gastric cancer during the period between 1979 and 1999, had been administered rhubarb before the development of gastric cancer. Among the 10 enrolled patients, only 2 patients had been administered rhubarb before the development of gastric carcinoma. The other 8 patients had never received rhubarb before the development of gastric carcinoma. Rhubarb use may have little connection with the development of gastric cancer in practice, even if some ingredients in rhubarb have shown carcinogenic activity in experimental studies.

Aged↗

PubMed2002

Suppressive effect of hochu-ekki-to on collagen induced arthritis in DBA1J mice.

OBJECTIVE: To investigate the effect of hochu-ekki-to (HET) decoction on the development of collagen-induced arthritis (CIA) in mice. METHODS: CIA was induced in male DBA/IJ mice by immunization with 2 injections of bovine type II collagen (CII). HET was orally administered at different doses and with different schedules. The incidence of arthritis, arthritis index, levels of anti-CII antibody, interleukin 6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) and lymphocyte subsets were examined. RESULTS: HET caused suppression of CIA development in a dose dependent fashion and exerted a suppressive effect on CIA when administered from the first CII immunization or from the onset of CIA, but not when administered for 2 weeks before CII immunization. HET inhibited the production of specific anti-CII antibody, IL-6, and TNF-alpha, and tended to normalize the proportions of cells in lymphocyte subsets. CONCLUSION: HET suppresses the development of CIA, and HET redistributes the population of lymphocytes in lymph node and blood and inhibits IL-6 and TNF-alpha secretion in CIA mice.

Adjuvants, Immunologic↗

PubMed2002

Frequent polymorphic changes but rare tumor specific mutations of the LATS2 gene on 13q11-12 in esophageal squamous cell carcinoma.

We previously reported that loss of heterozygosity on 13q12-13 is related with poor prognosis of esophageal cancer. However, a target tumor-suppressor gene on this region is not yet identified. Recently, LATS2, a new human homologue of the Drosophila tumor suppressor gene (lats/warts) was identified on 13q11-12. We therefore screened esophageal tumor cell lines and tumor tissues to detect tumor specific mutations of the LATS2 gene. Although we found 5 different polymorphisms in this gene (4 kinds of single-base changes and a 6-bp insertion), a tumor specific mutation was identified in only one out of 60 tumor tissues. These results indicated that the LATS2 gene is inactivated in only a small part of esophageal tumors, if any.

Carcinoma, Squamous Cell↗

PubMed2002

Inhibitory effects of epigallocatechin-3-gallate on N-nitrosomethylbenzylamine-induced esophageal tumorigenesis in F344 rats.

The present study was conducted to assess the inhibitory effects of EGCG (epigallocatechin-3-gallate) on NMBA-induced rat esophageal tumorigenesis and to seek the potential mechanisms. In experiment I, 81 F344 rats were randomly divided into seven experimental groups according to the different regiments of NMBA 1 mg/kg subcutaneously (s.c.) and EGCG 4 mg/kg or 10 mg/kg orally or intraperitoneally (i.p.). The experiment was terminated at 24 weeks. In experiment II, 48 rats were allocated into two groups, each group contained 24 rats, in which the rats were injected with NMBA 1 mg/kg only or a combination of NMBA 1 mg/kg and EGCG 4 mg/kg i.p. Six rats from each group were sacrificed at the 12th, 16th, 20th and 24th week, respectively. The expression of cyclin D1 and cyclooxygenases (COX-2 and COX-1) was detected using semi-quantitative RT-PCR, and the production of prostaglandin E2 (PGE2) was measured by ELISA. In the groups which were treated with EGCG at a dose of 4 mg/kg i.p., or 10 mg/kg both orally and i.p., the mean number of tumors per rat was significantly reduced to 48, 56 and 61%, respectively (p<0.05). The incidence rate of esophageal carcinomas in the rats that were treated with EGCG 4 mg/kg i.p., was significantly lower than that in the rats which only received NMBA 1 mg/kg (p<0.05). The expression of cyclin D1 and COX-2, and the levels of PGE2 were also decreased by EGCG treatment. These results indicated that EGCG significantly inhibits the NMBA-induced rat esophageal carcinogenesis and it inhibitory effects may partly target cyclin D1 and COX-2 expression, and PGE2 production.

Animals↗

PubMedDate not supplied

Paratracheal lymph node metastasis is associated with cervical lymph node metastasis in patients with thoracic esophageal squamous cell carcinoma.

BACKGROUND: We determined which lymph node metastases were associated with cervical lymph node metastases of thoracic esophageal squamous cell carcinoma. METHODS: A total of 6464 lymph nodes derived from 155 consecutive patients with thoracic esophageal squamous cell carcinoma were stained by immunohistochemistry (antibody: AE1/AE3). Lymph node metastases were mapped according to the mapping scheme of the American Thoracic Society, as modified by Casson et al. (Ann Thorac Surg 1994;58:1569-70). Patients were divided into two groups: those with and without cervical lymph node metastasis (CLNM). Mapping data were examined by uni- and multivariate analysis. RESULTS: Hematoxylin and eosin-positive and AE1/AE3-positive lymph node metastases were found in 59% and 77% of patients, respectively. Twenty-one (55%) of 38 patients in the CLNM(+) group and 30 (26%) of 117 patients in the CLNM(-) group had AE1/AE3-positive lymph node metastasis in the thoracic paratracheal lymph node. Paratracheal lymph node metastasis is only one independent factor for (CLNM), whereas upper thoracic paraesophageal lymph node and pulmonal hilar lymph node status were also significant in univariate analysis. Three (43%) of seven patients with cervical jumping metastasis from the thoracic esophagus had micrometastasis in the paratracheal lymph node. CONCLUSIONS: The paratracheal lymph node is most associated with (CLNM) of thoracic esophageal squamous cell carcinoma.

Aged↗

PubMedDate not supplied

Promotion effects of hot water on N-nitrosomethylbenzylamine-induced esophageal tumorigenesis in F344 rats.

This study is to determine the effects of hot water on N-nitrosomethylbenzylamine (NMBA)-induced rat esophageal tumorigenesis model. F344 rats received one treatment of hot water 1 ml/kg and NMBA 1 mg/kg, or a combination treatment of NMBA 1 mg/kg pus hot water 1 ml/kg, or/and EGCG (epigallocatechin-3-gallate) 10 mg/kg. The experiment was concluded at the 20th week. Our results showed that the number of tumors and incidence of carcinomas were significantly increased by hot water (65 degrees C) (p<0.05, p<0.03, respectively), as compared with the group which received NMBA injections only. EGCG treatment did not significantly reduce the number or the size of tumours as the temperature of added hot water increased. In addition, PGE2 production was induced by NMBA, and further significantly increased by added hot water (p<0.05). On the other hand, EGCG slightly decreased the elevated PGE2 production, however, this effect of EGCG was offset by hot water. Our study further confirmed that the drinking of hot beverages increased the risk of esophageal carcinogenesis, and the drinking hot tea will abolish the inhibitory effects of EGCG on this disease.

Animals↗

PubMedDate not supplied

Portal embolization in various types of liver: novel variables to predict hypertrophy.

BACKGROUND/AIMS: The aim of this study was to investigate the hypertrophic effect of portal embolization in various types of liver and clarify useful variables, for predicting efficacy of portal embolization. METHODOLOGY: Portal embolization was performed for 46 patients with hepatocellular carcinoma (n = 30), biliary tract cancer (n = 9), or metastatic liver tumors (n = 7). The hypertrophic effect of portal embolization in relation to diseases, clinical liver conditions, histological fibrosis, and liver function were examined. RESULTS: The hypertrophic effect of portal embolization was impaired in the patients with hepatocellular carcinoma, chronic hepatitis/cirrhotic liver, and advanced liver fibrosis. ICGR15 (indocyanine green dye retention rate at 15 minutes) was revealed to be an independent adverse predicting factor. Especially in hepatocellular carcinoma patients, platelet count was significantly correlated with the hypertrophy ratio. In patients who underwent major hepatectomy for hepatocellular carcinoma, not only the incidences of posthepatectomy liver failure but also survival rate were similar between patients with and without portal embolization, although patients with portal embolization originally had a limited liver function. CONCLUSIONS: Preoperative portal embolization made major hepatectomy possible in hepatocellular carcinoma patients, although portal embolization was less effective compared with other diseases. ICGR15 and platelet count may be novel variables to predict the hypertrophic effect of portal embolization in all and hepatocellular carcinoma patients, respectively.

Adult↗

PubMedDate not supplied

High serum soluble E-selectin levels are associated with postoperative haematogenic recurrence in esophageal squamous cell carcinoma patients.

E-selectin has been reported to be associated with haematogenic metastasis in various cancer patients. In order to evaluate the risk of postoperative haematogenic recurrence of esophageal squamous cell carcinoma (SCC) patients, we examined the preoperative serum levels of soluble E-selectin and clinicopathological data of the patients. Preoperative serum was obtained from 135 esophageal SCC patients who received esophagectomies from 1990 to 1998. Serum soluble E-selectin levels were measured by means of enzyme linked immunoreactive synthesis assay (ELISA). The expression of sialyl Lewis A and X antigens were evaluated in 58 out of 135 patients. Thirty-five patients (25.9%) had haematogenic recurrence in their postoperative course. Serum soluble E-selectin levels of the haematogenic recurrence group (mean 55.6 ng/ml) were significantly higher than those of the non-haematogenic recurrence group (mean 41.1 ng/ml). When the cut-off level of soluble E-selectin was 56 ng/ml, the logistic regression analysis showed that high serum soluble E-selectin levels, lymph node metastasis and intraepithelial spread were associated with postoperative haematogenic recurrence of the esophageal SCC patients (OR 2.99, p=0.047, OR 4.94, p=0.009 and OR 5.0, p=0.019. respectively). Univariate analysis revealed that the patients with a high serum soluble E-selectin level tended to have poor survival (p=0.078) and Cox multivariate analysis revealed that a high serum soluble E-selectin level was a prognostic factor in esophageal SCC patients (RR 1.84, p=0.065). The patients with a high serum soluble E-selectin concomitant with expression of sialyl Lewis antigens had a significant risk of postoperative haematogenic recurrence (p=0.005). These results indicated that preoperative high serum soluble E-selectin was a risk factor in the development of postoperative haematogenic recurrence and was a prognostic factor in esophageal SCC patients.

Biomarkers, Tumor↗