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Biomedical subjects

Shingo Ishiguro

Publications and source records attributed to Shingo Ishiguro.

48 records · Page 3Linked to original sources

Significance of the association between heparin-binding epidermal growth factor-like growth factor and CD9 in human gastric cancer.

Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a member of the EGF family. Juxtacrine activity of proHB-EGF (the membrane-anchored form of HB-EGF) has been shown to be significantly potentiated when it is coexpressed with CD9 in vitro. The purpose of our study was to investigate the issue of whether proHB-EGF and CD9 are coexpressed in gastric cancer. HB-EGF gene expression and protein production in human gastric cancers was investigated, and EGF receptor and CD9 expressions were also evaluated. HB-EGF mRNA levels in gastric cancers were elevated, compared with normal gastric tissues, especially in the intestinal type. ProHB-EGF immunoreactivity was detected primarily in the cytoplasm and plasma membrane of gastric cancer cells. Of 66 patients, 40 (60.6%) exhibited proHB-EGF immunoreactivity and the level of its expression was significantly associated with tumor status (p < 0.01) and histological differentiation (p < 0.001). In addition, proHB-EGF mRNA was detected at high levels in the intestinal type by in situ hybridization. CD9 immunoreactivity was found to be preserved in 26 of 36 patients (72.2%) and CD9 protein expression was inversely associated with lymph node status (p < 0.05). A significant correlation between its expression and histological differentiation (p < 0.01) was found, and the association of CD9 with proHB-EGF was increased in the intestinal type, as evidenced by an immunoprecipitation method. These results indicate that the coexpression of proHB-EGF and CD9 may be involved in the tumorigenesis and/or proliferation of gastric cancers in a juxtacrine manner.

Adult↗

Expression of smooth muscle calponin in tumor vessels of human hepatocellular carcinoma and its possible association with prognosis.

BACKGROUND: Hepatocellular carcinoma (HCC) is a vascular-rich tumor. The tumor vessels in HCC were demonstrated to have alpha-smooth muscle actin positive smooth muscle cells (SMCs). However, it is unclear whether the SMCs in the wall of the tumor vessels are differentiated or undifferentiated. Basic calponin is an actin-, tropomyosin-, and calmodulin-binding protein, and expression of the calponin gene in SMCs has been recognized as one of the late stage differentiation markers of SMCs. The authors investigated the differentiation state of SMCs in tumor vessels by immunohistochemical examination of calponin in patients with HCC, and whether it is associated with the patients' prognosis. METHODS: Tumor and nontumor tissues were obtained from 75 patients with HCC who underwent radical hepatic resection. The differentiation state of the smooth muscle cells were evaluated based on the expression level of calponin, an actin-binding protein, using immunohistochemistry and reverse transcription-polymerase chain reaction analysis. The disease free survival (DFS) rates were estimated according to the Kaplan-Meier method comparing groups of patients with calponin positive and negative tumor vessels. A multivariate analysis based on the Cox proportional hazards regression model was performed to estimate whether the expression of calponin is an independent prognostic factor. RESULTS: In the 75 patients with HCC examined, 36 patients (48%) possessed calponin positive SMCs, and the remaining 39 (52%) did not. There were no significant differences in either clinical or pathologic factors between the two groups of patients. The 5- and 8-year DFS rate of the patients with calponin positive vessels were 37% and 26%, respectively. These values were significantly higher (11% and 5%) than those of patients with calponin negative vessels. Gender, TNM classification, perioperative transfusion, and calponin expression were found to be independent prognostic factors for DFS. CONCLUSIONS: Immunohistochemical examination of the calponin expression in the tumor vessels is a new and useful means to predict the prognosis of HCC patients after hepatic resection.

Aged↗

Cytokeratin deposits in lymph nodes show distinct clinical significance from lymph node micrometastasis in human esophageal cancers.

BACKGROUND: Cytokeratin immunostaining is the most common method used to identify micrometastatic cancer cells from the lymph nodes. However, contamination with hyalinized cytokeratin particles, frequently observed in the lymph nodes of esophageal cancer patients, can lead to misinterpretation of cytokeratin immunostaining. MATERIALS AND METHODS: Cytokeratin immunostaining (AE1/AE3) of surgically removed lymph nodes was performed for 41 cases of node-negative, but locally advanced (T3, T4), esophageal cancer patients. Cytokeratin immunoreactivity (CK) was classified as micrometastasis (MM) or cytokeratin deposit (CD) by the presence or absence of tumor nuclei in serial sections given hematoxylin-eosin staining. RESULTS: CK (+) was observed in 18 patients (44%), including 11 with MM (+) (27%) and 10 with CD (+) (24%). There was no correlation between MM and CD, and neither was associated with clinicopathological factors, except for a high incidence of preoperative chemotherapy in CD (+) patients. The presence of CK did not affect postoperative survival of esophageal cancer patients at this limited stage, showing a 5-year survival rate of 57% for CK (+) and 64% for CK (-) (P = 0.6064). Interestingly, patients with MM (+) showed poorer prognosis than MM (-) (5-year survival: 28% vs 79%, P = 0.0188), while CD (+) patients tended to display better prognosis than CD (-) ones (5-year survival: 78% vs 56%, P = 0.1860). CONCLUSIONS: Evaluation by cytokeratin immunostaining of lymph nodes requires careful discrimination of CD from MM, in order to allow MM to be used as a prognostic factor for esophageal cancer patients.

Esophageal Neoplasms↗

Expression of p57/Kip2 protein in extrahepatic bile duct carcinoma and intrahepatic cholangiocellular carcinoma.

BACKGROUND: Evaluation of the biological character of carcinomas requires understanding of cell cycle regulators. P57 (Kip2) belongs to the Cip/Kip family and is known to be one of the universal negative regulators of cell cycle. METHODS: In the present study, therefore, we investigated p57 expression in 37 extrahepatic bile duct carcinomas (BDC) and 28 intrahepatic cholangiocellular carcinomas (CCC). RESULTS: The average p57 labeling index (LI) in BDC and CCC were 60.8 +/- 7.9 and 58.6 +/- 18.6, respectively, which were significantly lower (p = 0.0008 and p = 0.0408, respectively) than those in normal duct epithelia (73.1 +/- 7.9, 70.4 +/- 8.2). p57 LI was significantly lower in BDC and CCC cases with biological aggressive phenotypes such as poor differentiation (p = 0.0260 and p = 0.0069), lymph node metastasis (p = 0.0274 and p = 0.0214), high Ki-67 LI (p = 0.0164 and p = 0.0343) and cyclin D1 overexpression (p = 0.0359 and p = 0.0255). CONCLUSION: These findings suggest that decreased p57 expression is related to the increased activity of cell proliferation and also the progression of these carcinomas.

Adult↗

Polaprezinc attenuates Helicobacter pylori-associated gastritis in Mongolian gerbils.

BACKGROUND: The ammonia-monochloramine system plays an important role in Helicobacter pylori-associated gastric mucosal injury. Polaprezinc, a new antiulcer agent, has a scavenging action against monochloramine. The aim of the experiment was to investigate the inhibitory effects of polaprezinc on the H. pylori-induced gastritis in Mongolian gerbils. MATERIALS AND METHODS: Mongolian gerbils fasting for 24 hours were orally given culture broth containing 2-4 x 10(8) colony-forming units of H. pylori ATCC 43054 per milliliter. From 4 hours after inoculation until the end of the experiment, gerbils were given chow pellets with or without 0.02% polaprezinc. All gerbils were killed 12 weeks later. The grades of H. pylori density and histologic features of gastritis were evaluated in accordance with the Updated Sydney System. The scavenging effect of polaprezinc on monochloramine was investigated spectrophotometrically. RESULTS: Polaprezinc had little or no influence on the H. pylori density in both pyloric and fundic mucosae. However, it significantly attenuated the development of polymorphonuclear neutrophil activity, mononuclear infiltration, and surface epithelial erosion in both pyloric and fundic mucosae compared with those of the control group. H. pylori inoculation significantly increased the heights of both pyloric and fundic mucosae (mainly due to the increased height of foveolar hyperplasia), but polaprezinc inhibited the increase of mucosal thickness in both pyloric and fundic mucasae. No intestinal metaplasia was detected in this study. Spectrophotometric examination revealed that polaprezinc scavenged monochloramine. CONCLUSIONS: Polaprezinc inhibited the development of H. pylori-induced gastritis through its scavenging action against monochloramine.

Animals↗

Expression of S100A6 and S100A4 in matched samples of human colorectal mucosa, primary colorectal adenocarcinomas and liver metastases.

OBJECTIVE: S100A6 and S100A4, two of S100 protein family, have been suggested to be associated with cancer tumorigenesis and metastasis. The aim of this study was to evaluate the expression levels of S100A6 and S100A4 in matched samples of primary human colorectal adenocarcinomas (T), adjacent normal colorectal mucosa (N) and liver metastases (M). This gave us the advantage of directly comparing levels of S100A6 and S100A4 expression within the same genetic background. METHODS: In matched samples of N, T and M from 10 colorectal adenocarcinoma patients, expressions of S100A6 and S100A4 were studied by Western blot and immunohistochemical analyses using specific antibodies against each protein. RESULTS: The expression levels of S100A6 were significantly higher in T than in N (p < 0.05), while those of S100A4 showed no difference between T and N. There were no significant differences in the expression levels of S100A6 or S100A4 between M and T. Similar results were obtained by immunohistochemical analysis. Moreover, S100A6 was stained more intensely in invading fronts than in central portions of both T and M. CONCLUSIONS: The observed differential expression of S100A6 and S100A4 suggests that S100A6, rather than S100A4, is associated with human colorectal adenocarcinoma tumorigenesis and invasion/metastasis.

Adenocarcinoma↗

Expression of platelet-derived endothelial cell growth factor/thymidine phosphorylase in cervical intraepithelial neoplasia.

Angiogenesis contributes to the growth and secondary spreading of solid tumors. Platelet-derived endothelial cell growth factor (PD-ECGF)/thymidine phosphorylase (TP) has been identified as such an angiogenic factor. In this study, the expression of PD-ECGF/TP and VEGF was evaluated by immunohistochemical staining of tumor specimens from 40 patients with cervical intraepithelial neoplasia (10 with moderate dysplasia; 10 with severe dysplasia; 10 with carcinoma in situ; 10 with invasive carcinoma). The microvessel density was assessed by immunostaining for factor VIII-related antigen in the most highly neovascularized area. In both the nucleus and cytoplasm, the intensity of PD-ECGF/TP expression in carcinoma in situ and invasive carcinoma was significantly stronger than that in moderate dysplasia. However, the intensity of VEGF expression was not significantly different in the various specimens. The microvessel density in mild dysplasia was significantly different from that in carcinoma in situ (p<0.05), and that in invasive carcinoma (p<0.05). There was no significant relationship between the microvessel density and the expression of PD-ECGF/TP or that of VEGF. These results show that the expression of PD-ECGF/TP appears to be involved in the promotion of angiogenesis in cervical intraepithelial neoplasia.

Carcinoma in Situ↗

Time trends for small gastric cancer in Japan.

BACKGROUND: Gastric cancer rates in Japan have been declining since the 1970s. The rate of differentiated carcinomas has decreased and that of undifferentiated carcinomas has increased. However, little is known about the time trends of small gastric cancer. The aim of this study was to investigate the trends of small gastric cancer over time in Japan. METHODS: We reviewed cases of small gastric cancer (less than 20 mm in diameter) in two groups of patients who entered the age range of 55-to-67 years 14 years apart: patients in cohort 1 (n = 66) were born between 1899 and 1912, and those in cohort 2 (n = 66) were born between 1926 and 1936. Between-group comparisons were made for macroscopic, microscopic, and histochemical findings. Mucin histochemical analysis was used to investigate gastric and nongastric phenotypes. Helicobacter pylori was also investigated by immunohistochemistry. RESULTS: There were significant decreases in the incidence of elevated carcinoma (20% in cohort 1 vs 6% in cohort 2; P < 0.05) and papillary adenocarcinoma (11% vs 2%; P < 0.05). The incidence of flat carcinomas was significantly increased (3% vs 15%; P < 0.05). The incidence of tumors surrounded by fundic gland mucosa increased (20% vs 29%), whereas that of tumors surrounded by intestinal metaplastic mucosa decreased (52% vs 41%). The rate of H. pylori infection in mucosa surrounding tumors was the same in both groups (35%). The incidence of tubular adenocarcinoma with gastric-type mucin was higher in cohort 2 (64%) than in cohort 1 (51%). CONCLUSION: The rate of tubular adenocarcinomas containing gastric type mucin has increased over time. These tumors had a tendency to develop in the fundic gland mucosa and to show less intestinal metaplasia. The H. pylori infection rate was unrelated to this time trend. In advanced gastric cancer, the differentiated carcinoma rate has decreased; however, in small gastric cancer, the rate of tubular adenocarcinoma containing gastric type mucin has increased. This suggests that tubular adenocarcinoma with gastric type mucin changes into poorly differentiated adenocarcinoma as tumors grow to advanced stages.

Journal Article↗

Off-pump axillo-coronary artery bypass grafting with porcelain aorta.

Coronary artery bypass grafting (CABG) in patients with severely diseased ascending aorta has been associated with high risk for cerebral vascular accidents due to atheromatous embolism. In this situation, aortic no-touch techniques are widely employed as most important surgical strategy to prevent these complications. A case of 75-year-old man with effort angina associated with porcelain ascending aorta was reported here. He successfully underwent off-pump axillo-coronary bypass grafting with saphenous vein graft and has remained uneventful during his follow-up period. The off-pump axillo-coronary artery bypass grafting seemed to be an appropriate procedure for coronary revascularization with severely diseased ascending aorta.

Aged↗