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Biomedical subjects

F Shimamoto

Publications and source records attributed to F Shimamoto.

88 records · Page 5Linked to original sources
PubMed1982

Enhanced effect of gastrin on rat stomach carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine.

This study deals with the effects of gastrin on the incidence of gastric tumors in rats induced by N-methyl-N'-nitro-N-nitrosoguanidine. Inbred Basel-Wistar rats received N-methyl-N'-nitro-N-nitrosoguanidine in drinking water (50 micrograms/ml for 32 weeks) in order to produce gastric carcinoids. A treatment with s.c. injection of pentagastrin (300 micrograms/kg, once daily for 4 weeks) was started at the beginning of N-methyl-N'-nitro-N-nitrosoguanidine treatment simultaneously, on the 4th, 8th, 16th, and 32nd week after start of N-methyl-N'-nitro-N-nitrosoguanidine treatment, respectively. At autopsy, from the 55th to 60th week after start of the experiment, only in the eighth-week group of gastrin-treated rats was the incidence of gastric carcinoid significantly higher than in the gastrin-untreated group of rats receiving N-methyl-N'-nitro-N-nitrosoguanidine alone. The incidence of adenocarcinoma in the glandular stomach also was high only in the fourth-week group of gastrin-treated rats. However, these effects could not be seen in other gastrin-treated or untreated groups of rats. The data suggest that gastrin treatment in the early stage of rat stomach carcinogenesis by N-methyl-N'-nitro-N-nitrosoguanidine is effective in increasing the development of gastric tumors.

Adenocarcinoma↗
PubMed1981

Induction of carcinoids in the glandular stomach of rats by N-methyl-N'-nitro-N-nitrosoguanidine.

A total of 30 inbred Wistar rats were orally administered 70 microgram/ml solution of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) for 35 weeks and then tap water for the following 20 to 30 weeks. Four of the 20 females and two of ten males developed carcinoids in the glandular stomach, but no metastasis could be found. Carcinoids developed most frequently in the fundic portion along the greater curvature. Histologically, these tumors were medullary anaplastic carcinomas containing two different endocrine cell populations. The first cell type was argentaffin having the electron-dense, somewhat pleomorphic secretory granules (437-810 nm) and the second type was argyrophil having round granules with a dense core and a pale halo (550 nm). None of these tumors showed endocrine immunoactivity for gastrin, somatostatin, insulin, glucagon, and enkephalin. One of these gastric tumors developed into scirrhous carcinoma, but differentiated adenocarcinoma could not be seen in the glandular stomach.

Animals↗
PubMedDate not supplied

Immunoreactive MUC1 expression at the deepest invasive portion correlates with prognosis of colorectal cancer.

This study sought to examine the relationship between MUC1 expression at the deepest invasive portion, invasive/metastatic potential, and prognosis of colorectal cancer in relation to cellular proliferation. MUC1 expression was detected immunohistochemically using KL-6 antibody (anti-MUC1 monoclonal antibody) in 100 surgically resected specimens of advanced colorectal cancer. Distinct staining of the luminal surfaces, defined as positive immunoreactive (IR)-MUC1 expression, was seen in more than 30% of the tumor cells at the deepest invasive portion. The proliferating cell nuclear antigen labeling index (PCNA-LI) was also examined in the same areas. IR-MUC1 expression was detected in 71 (71%) of 100 lesions. Lesions with lymphatic or venous invasion showed a significantly higher incidence of IR-MUC1 expression than those without lymphatic or venous invasion (80 vs. 42% and 82 vs. 61%, respectively). Lesions with lymph node metastasis showed a significantly higher incidence of IR-MUC1 expression than those without lymph node metastasis (88 vs. 53%). Lesions with liver metastasis showed a significantly higher incidence of IR-MUC1 expression than those without liver metastasis (92 vs. 59%). Dukes' stage was also significantly correlated with IR-MUC1 expression. The incidence of IR-MUC1 expression did not significantly differ with regard to histologic subclassification and depth of invasion. There was no significant correlation between IR-MUC1 expression and the PCNA-LI. IR-MUC1 expression at the deepest invasive portion revealed a significant correlation with prognosis; furthermore, in patients with better differentiated lesions, in those with lesions confined to muscularis propria or subserosa (subadventitial) invasion, in those with Dukes' B and C, or in those undergoing curative resection, IR-MUC1 expression significantly correlated with prognosis. Patients with high PCNA-LI lesions showed a significantly poorer prognosis than those with low PCNA-LI lesions. Only in patients undergoing curative resection, patients with IR-MUC1-positive and high PCNA-LI lesions showed a significantly poorer prognosis than those with IR-MUC1-negative and low PCNA-LI lesions. The significant risk factors in the order of poorer prognosis in patients undergoing curative resection by the multivariate analysis were the histologic grade (moderately-poorly, poorly or mucinous adenocarcinomas), IR-MUC1 expression, and lymph node metastasis. These results indicate that IR-MUC1 expression is an important predictor of the metastatic potential and the prognosis of colorectal cancer, independent of histologic grade, depth of invasion or cellular proliferative activity. Combined analysis of IR-MUC1 and histologic grade, and combined expression of IR-MUC1 and PCNA at the deepest invasive portion are especially useful in predicting colorectal cancer prognosis.

Aged↗
PubMedDate not supplied

Combined expression of HLA-DR antigen and proliferating cell nuclear antigen correlate with colorectal cancer prognosis.

HLA-DR antigen expression and the proliferating cell nuclear antigen labeling index (PCNA-LI) were examined immmunohistochemically in 59 surgically resected advanced colorectal cancers to clarify the clinicopathologic significance of the HLA-DR antigen. HLA-DR antigen expression was detected in 33 (56%) of the 59 lesions, which showed less frequent liver metastasis than lesions without HLA-DR antigen expression (40 vs. 68%; p < 0.05). Five-year survival rates of patients with and without HLA-DR antigen expression were 50 and 19%, respectively. Lesions combining HLA-DR antigen expression and a relatively low PCNA-LI had the best prognosis. These results indicate that HLA-DR antigen expression, particularly combined with a low PCNA-LI, is an important outcome predictor in colorectal cancer.

Aged↗
PubMedDate not supplied

The clinical significance of the histologic subclassification of colorectal carcinoma.

According to the histologic features at the deepest level of tumor invasion (the tumor apex), we classified colorectal carcinomas as follows: well differentiated (W), moderately differentiated (M), and mucinous (Muc). By assessing its glandular configuration and cellular arrangement, the M type was further subdivided in to two different groups: moderately well differentiated (Mw) and moderately poorly differentiated (Mp) carcinomas. In our sample there were 56 W, 53 Mw, 20 Mp and 13 Muc tumors. The malignant potential of each tumor was evaluated by examining for the presence or absence of lymphatic invasion, venous invasion, lymph node metastases and liver metastases. In comparison with the other tumors, the Mp tumors proved to harbor the highest malignant potential, exhibiting a higher incidence of lymphatic invasion (95%, 19/20 of the cases), venous invasion (75%, 15/20 of the cases), lymph node metastases (80%, 16/20 of the cases), and liver metastases (40%, 8/20 of the cases). Colorectal carcinomas are composed of multiple cell populations with different biological and malignant properties, and through the histologic subclassification we could identify that Mp tumors have the highest potential to invade normal tissue and metastasize.

Antigens, Tumor-Associated, Carbohydrate↗
PubMedDate not supplied

Carcinoembryonic antigen staining patterns at the invasive tumor margin predict the malignant potential of colorectal carcinoma.

Immunohistochemical carcinoembryonic antigen (CEA) staining patterns at the invasive tumor margin were correlated with malignant potential in 64 advanced colorectal carcinomas. Twenty-two (34%) carcinomas showed an apical and 42 (66%) a cytoplasmic staining pattern. Carcinomas with a cytoplasmic pattern had a higher incidence of lymph node (71 versus 41%; p < 0.05) and liver (50 versus 23%; p < 0.05) metastasis and higher levels of serum CEA (p < 0.01) than those with an apical staining pattern. Nine of 11 recurrent tumors had a cytoplasmic pattern and 2 had an apical pattern (p < 0.05). Among carcinomas having the same degree of differentiation, those with a cytoplasmic CEA staining pattern were more aggressive. Six (55%) well-differentiated carcinomas with a cytoplasmic pattern metastasized to the liver while none with an apical pattern did (p < 0.05). Moderately differentiated carcinomas with a cytoplasmic pattern had a significantly higher incidence of lymph node metastasis than those with an apical pattern (77 versus 46%; p < 0.05). When colorectal carcinomas are examined at the invasive tumor margin, an evaluation of the CEA staining pattern is useful in recognizing carcinomas having a higher potential to metastasize and recur after curative surgery.

Adenocarcinoma↗
PubMedDate not supplied

Proliferating cell nuclear antigen expression correlates with the metastatic potential of submucosal invasive colorectal carcinoma.

To examine the malignant potential of submucosal invasive colorectal carcinoma, the relationship between proliferating cell nuclear antigen (PCNA) expression and clinicopathologic risk factors for lymph node metastasis was studied in 149 patients with submucosal invasive colorectal carcinoma. The depth of submucosal invasion was classified as scanty or massive. Histologic subclassification at the submucosal deepest invasive portion was done as follows: well differentiated (W), moderately well differentiated (Mw), moderately poorly differentiated (Mp) or poorly differentiated (Por). Tumor growth was divided into polypoid growth and nonpolypoid growth. The PCNA expression (labeling index, LI) was examined at the submucosal deepest invasive portion. The PCNA-LI of tumors showing lymph node metastasis (mean, 56.5 +/- 19.0%) was significantly higher than that of tumors without lymph node metastasis (mean, 41.5 +/- 19.3%; p < 0.01). The PCNA-LI of Mp tumors (mean, 57.7 +/- 16.5%) was significantly higher than that of W (mean, 38.5 +/- 19.0%; p < 0.05) and Mw (mean, 43.7 +/- 19.1%; p < 0.05) tumors. The PCNA-LI of tumors without adenomatous features (mean, 47.9 +/- 20.5%) was significantly higher than that of tumors with such features (mean, 37.1 +/- 17.1%; p < 0.05). The PCNA-LI was not correlated with other risk factors for lymph node metastasis, such as lymphatic invasion, depth of submucosal invasion, macroscopic type, and growth pattern. These results indicate that the PCNA-LI may be useful marker for predicting the potential metastases to lymph nodes in submucosal invasive colorectal carcinoma, while the proliferative activity of cancer cells correlates with the degree of the differentiation in the area of deepest invasion.

Antibodies, Monoclonal↗
PubMedDate not supplied

Flat-elevated colorectal neoplasms exhibit a high malignant potential.

The potential of flat-elevated colorectal adenomas to undergo rapid malignant transformation and progression to invasive carcinoma is still under discussion. Therefore, a total of 130 colorectal neoplastic lesions > or = 1 cm in diameter were examined after endoscopic or surgical resection. Lesions were macroscopically classified into three categories: (1) flat elevation (22 lesions), superficially elevated lesion with a smooth surface; (2) granular laterally spreading tumor (GLST; 26 lesions), laterally spreading aggregates of nodules forming a lesion with granular surface, and (3) polypoid (82 lesions), pedunculated, subpedunculated and sessile polyps. The adenomatous component showed a tubulovillous architecture in 9/26 (35%) of GLST and 18/82 (22%) of polypoid lesions, however none of the flat-elevated lesions had a villous component (p <0.01; p <0.05). Carcinoma was present in 17/22 (77%) flat elevations, 37/82 (45%) polypoid lesions and 11/26 (42%) GLST (p <0.05). None of the carcinomas arising in GLST and only 1/37 (3%) of those developing in polypoid lesions were invasive carcinomas, but 4/17 (24%) carcinomas arising in flat elevations showed submucosal invasion. Moreover, while all 5 noncancerous flat elevations showed severe atypia, 17/82 (21%) polypoid lesions and 5/26 (19%) GLST showed moderate atypia. In conclusion, flat-elevated colorectal neoplasms have a high malignant potential and the role of these lesions as precursors of colorectal carcinomas deserves greater emphasis.

Adenoma↗
PubMedDate not supplied

Predictive value of cathepsin D and Ki-67 expression at the deepest penetration site for lymph node metastases in gastric cancer.

To search for reliable predictors for lymph node metastasis, we immunohistochemically analyzed surgically resected gastric cancer specimens that showed invasion of submucosa (sm) and muscularis propria (mp) of the tumor. The analysis investigated cathepsin D and Ki-67 expression in 136 specimens that were divided into an sm1/sm2 group and an sm3/mp group. In sm1/sm2 group, the incidence of lymph node metastases was significantly higher in tumors with high Ki-67 labeling index (LI) (44%) than in those with low Ki-67 LI (0%). In sm3/mp group, the incidence of lymph node metastases was significantly higher in cathepsin D-positive (56%) and high Ki-67 LI tumors (64%) than in cathepsin D-negative (33%) and low Ki-67 LI (33%). Combined analysis of cathesin D expression and Ki-67 LI correlated strongly with lymph node metastases. No lesions with cathepsin D-negative expression and low Ki-67 LI had lymph node metastases in either group. Cathepsin D and Ki-67 expression may be useful predictors for lymph node metastases in gastric cancer with sm and mp invasion. As predictors, they can identify lesions without lymph node metastases and indicate lesions not needing additional treatment after endoscopic mucosal resection and laparoscopic gastrectomy.

Adult↗
PubMedDate not supplied

Conditions of curability after endoscopic resection for colorectal carcinoma with submucosally massive invasion.

The deepest invasive portion of colorectal carcinoma (CRC) is considered to be the part, which ultimately will invade, spread locally and give metastasis. We have previously reported that histologic differentiation at the deepest invasive portion of CRC closely correlate with metastatic potential and is useful in understanding the curability of endoscopic mucosal resection (EMR). The aim of this study is to clarify the conditions of curative EMR for CRC with submucosally (sm) massive invasion. A total of 521 cases with sm invasive CRC (Group A, 470 surgically resected cases; Group B, 51 followed-up cases after EMR) were studied. The depth of sm invasion was defined as the practically measured distance from muscularis mucosae. Histologic subclassification was performed at the deepest invasive tumor margin as: well-differentiated (W), moderately differentiated (M) and poorly differentiated (Por). By assessing glandular configuration and cellular arrangement, M type was further subdivided into two different groups; moderately-well differentiated (Mw) and moderately-poorly differentiated (Mp). In group A, lymph node (LN) metastasis was detected in 45 (9.6%) of 470 cases. W or Mw lesions showed LN metastasis in 4.9% (19/388). Mp or Por lesions showed LN metastasis in 37.3% (25/67) (W/Mw vs Mp/Por; p<0.01). Of 45 cases with LN metastasis that could be measured the practical distance of sm invasion, W or Mw lesions showed no LN metastasis in cases within 1,500 micrometer invasion. However, Mp or Por lesions showed LN metastasis in cases within 1,500 micrometer invasion (5/15, 33.3%, minimum 400 micrometer invasion; so-called scanty invasion). In group B, none of 51 cases died of LN metastasis and showed no other metastasis, although 17 cases (33.3%) showed an sm invasion more than 1,500 micrometer. These results indicated that CRC even with sm massive invasion can be cured by complete EMR on conditions that the depth of sm invasion is within 1,500 micrometer and histologic grade at the deepest invasive portion is W or Mw, if there are no vessel involvement. However, cases with Mp or Por grade were not curative by EMR, even if they showed an sm scanty invasion.

Colorectal Neoplasms↗
PubMedDate not supplied

c-myc gene mutation in gastric mucosa-associated lymphoid tissue (MALT) lymphoma and diffuse large B-cell lymphoma.

The c-myc gene is involved in important cellular processes, including cell proliferation, differentiation, and apoptosis. We analyzed mutation of the c-myc gene in 51 patients with gastric lymphoma [27 patients with low-grade mucosa-associated lymphoid tissue (MALT) lymphoma, 11 with high-grade MALT lymphoma, and 13 with diffuse large B-cell lymphoma (DLL)], by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis. We also evaluated the relationship between mutation of the c-myc gene and regression of low-grade MALT lymphoma after Helicobacter pylori (H. pylori) eradication. Mutation in exon 2 of the c-myc gene was present in 2 of 20 (10%) patients with low-grade MALT lymphoma, in 1 of 7 (14%) patients with high-grade MALT lymphoma, and none of 10 patients with DLL. The 3 patients who had mutations of the gene, showed different patterns of mobility shift, suggesting different mutations. In addition, 15 patients with low-grade MALT lymphoma received anti-H. pylori therapy. All the patients achieved eradication. Nine of the 15 (60%) patients with low-grade MALT lymphoma showed complete regression (CR), 3 (20%) showed partial regression (PR), and 3 (20%) showed no change (NC). One of the 9 (11%) CR patients had a mutation of the c-myc gene. None of the 3 PR and 3 NC patients had mutation of the gene. There was no significant difference between the frequencies among the c-myc gene mutation in CR, in PR and in NC patients. These data suggest that mutation of the c-myc gene may not be commonly associated with development of gastric MALT lymphoma and DLL, and may not be associated with regression of low-grade MALT lymphoma after H. pylori eradication.

Anti-Ulcer Agents↗
PubMedDate not supplied

Microsatellite instability at D18S61 is associated with no regression of gastric mucosa-associated lymphoid tissue lymphoma after Helicobacter pylori eradication.

Recent studies have shown 70-80% of gastric low-grade mucosa-associated lymphoid tissue (MALT) lymphomas regressing in response to eradication of Helicobacter pylori (H. pylori). Genetic mechanism of regression of gastric MALT lymphoma after H. pylori eradication remains unclear. To clarify the issue, we evaluated microsatellite instability (MSI) at 12 microsatellite loci in 15 patients with gastric low-grade MALT lymphoma, who received eradication therapy of H. pylori. H. pylori infection was observed in all the patients. After eradication therapy of H. pylori, patients were observed for a median of 21 months (range, 6-49 months). Eradication was achieved in all the patients. Nine of the 15 (60%) patients showed complete regression (CR), 3 (20%) partial regression (PR), and 3 (20%) no change (NC). MSI was detected in 3 of the 15 (20%) patients with low-grade MALT lymphoma. Compared with response to eradication therapy of H. pylori, MSI was detected in 1 of the 12 (8%) CR and PR patients, and in 2 of the 3 (67%) NC patients. Especially, MSI at D18S61 was detected in 2 of the 3 (67%) NC patients but in none of the 12 CR and PR patients. There was a significant difference between frequency of MSI at D18S61 in NC patients and that in CR and PR patients (p<0.05). These data suggest that MSI at D18S61 may be associated with lack of regression of gastric MALT lymphoma after H. pylori eradication.

Anti-Ulcer Agents↗
PubMedDate not supplied

Hepatic resection with tumor thrombectomy for hepatocellular carcinoma with tumor thrombi in the major vasculatures.

BACKGROUND/AIMS: It is still controversial whether surgical or non-surgical treatments should be adopted for hepatocellular carcinomas (HCC) with tumor thrombi (TT) in the major vasculatures. We evaluate the effectiveness of and the indications for hepatic resection with tumor thrombectomy for such patients. METHODOLOGY: Seventeen patients with TT in the major vasculatures caused by HCC were enrolled. Eleven patients had Vp3 TT, 5 patients had Vv3 TT, and 1 patient had Vp3 and Vv3 TT, concurrently. Out of the 17 patients, 13 underwent hepatic resections with tumor thrombectomies and the remaining 4 received only hepatic resections without tumor thrombectomies. RESULTS: In patients with Vp3 TT, median and mean survival times were 7.8 and 18.5 months, respectively, and 1- and 5-year survival rates were 36.4% and 18.2%, respectively. In patients with Vv3 TT, median and mean survival times were 9.9 and 8.4 months, respectively. Patients who underwent hepatic resections with tumor thrombectomies had significantly better prognoses than those who did not receive tumor thrombectomies (p=0.0039). CONCLUSIONS: The prognosis of HCC patients with TT in the major vasculatures, who have relatively small primary tumors, good hepatic functional reserves and no distant metastases should be good, if hepatic resections with tumor thrombectomies are performed.

Adult↗
PubMedDate not supplied

pS2 expression as a possible diagnostic marker of colorectal carcinoma in ulcerative colitis.

This study was performed to evaluate the significance of pS2 and MUC1 expressions in ulcerative colitis (UC)-associated colorectal neoplasias. Tissues were collected from 6 patients with UC-associated colorectal neoplasias treated surgically. Specimens were 13 adenocarcinomas, 40 dysplasias (20 high-grade dysplasias, 20 low-grade dysplasias), and 60 normal mucosae. Tissues were also collected from patients without UC treated surgically or endoscopically. pS2, p53, and MUC1 expressions were examined immunohistochemically and compared. The K-ras codon 12 mutation was investigated by single-strand conformation polymorphism analysis. In patients with UC, the incidence of pS2 expression was significantly higher (p<0.01) in adenocarcinomas than it was in dysplasias, and no pS2 expression was seen in normal mucosae. p53 overexpression was detected in 50% (10/20) even in low-grade dysplasias. MUC1 expression was seen only in invasive carcinomas, but it was seen in 100% of cases (3/3). K-ras gene mutations were detected in 2 (20%) of 10 carcinomas. In low and high-grade dysplasias, the incidences of pS2 expression were significantly (p<0.01) lower than the incidences of p53 overexpression, however, in UC-associated carcinomas there was no significant difference; pS2 expression and p53 overexpression were detected in 13 of 13 (100%) cases and in 12 of 13 (92%) cases, respectively. These results suggest that p53 overexpression may be a diagnostic marker of neoplasia, and that pS2 expression may be a diagnostic marker of colorectal carcinoma in case of UC.

Adult↗
PubMedDate not supplied

Hepatic resection for intrahepatic cholangiocarcinoma: relation to gross tumor morphology.

BACKGROUND/AIMS: The aim of this study was to investigate the clinicopathologic features and biological behaviors related to the gross appearance of intrahepatic cholangiocarcinoma. METHODOLOGY: Fourteen patients with intrahepatic cholangiocarcinoma who underwent hepatic resection between 1986 and 1998 were divided into four groups according to the gross appearance of the tumor: ID (intraductal growth) type (n = 1), PD (periductal-infiltrating) type (n = 4), MF (mass-forming) type (n = 5), MF-with-PD type (n = 4). RESULTS: Overall survival at 1, 5, and 10 years was 50.0%, 35.7%, and 35.7%, respectively. All three long-term survivors without recurrence had tumors unassociated with vascular invasion, intrahepatic metastasis, or lymph node metastasis. The MF and MF-with-PD tumors were more frequently associated with vascular invasion and/or lymph node metastasis than the ID or PD type. The Ki-67-positive grade of the cancer cells was clearly higher in the MF and MF-with-PD tumors than in the ID or PD type. All of the cases of MF-with-PD tumors were stage IV-A and had a poor outcome. CONCLUSIONS: Extended hepatic resection with a sufficient surgical margin yielded good results in intrahepatic cholangiocarcinoma patients without vascular invasion, intrahepatic metastasis, or lymph node metastasis. However, it is necessary to develop a new effective strategy for advanced intrahepatic cholangiocarcinomas, such as the MF-with-PD type.

Aged↗