Biomedical subjects

A Miwa

Publications and source records attributed to A Miwa.

231 records · Page 13Linked to original sources

PubMedDate not supplied

Highly aggressive behavior and poor prognosis of small cell carcinoma in the stomach: flow cytometric and immunohistochemical analysis.

Small cell carcinoma of the stomach has an aggressive feature, and the survival rate of the patients is poor. The purpose of this study was to determine the clinical course, and effects of histopathologic characteristics of specific tumors including DNA contents and immunohistochemical aspects in patients with small cell carcinoma of the stomach. Medical records of 8 patients who presented with small cell carcinoma of the stomach were retrospectively reviewed. Primary tumors were studied by flow cytometric analysis and immunohistochemical staining for the p53 protein, PCNA (proliferating cell nuclear antigen), factor VIII related antigen (specific for endothelial cells), VEGF (vascular endothelial growth factor) and PD-ECGF (platelet-derived endothelial cell growth factor). DNA aneuploid was observed in 4 cases. Staining for the p53 product was positive in 50% of all the cases. The average PCNA labeling rate (LR) was 71.3+/-9.9%. Positive VEGF expression was found in 7 tumors and positive PD-ECGF expression was found in all tumors. The estimated median survival was 252 days for all the patients. Liver metastases were observed in 4 of the 8 patients, however, surgery and chemotherapy have given us one long-term survivor (43 months). Higher PCNA LR of small cell carcinoma may be an unfavorable characteristic of biological behavior. Moreover, both VEGF and PD-ECGF positivity are well-characterized inducers of hepatic metastasis.

Aged↗

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Apoptosis, cell proliferation and expression of oncogenes in gastric carcinomas induced by preoperative administration of 5-fluorouracil.

The purpose of this study was to examine the correlations among enhancement of apoptosis, cell proliferation and expression of oncogenes in gastric carcinomas induced by preoperative oral administration of 5-fluorouracil (5-FU). The occurrence of spontaneous apoptotic cell death in 42 patients with gastric carcinoma was analyzed in the biopsy specimens preoperatively. p53 status was examined by polymerase chain reaction-single strand confirmation polymorphism and sequencing. Fourteen patients received oral administration of 5-FU at 300 mg/body/day for 7 days preoperatively. For detection of apoptotic cells, apoptotic incidences (AIs) were examined by the terminal deoxynucleotidyl transferase-mediated deoxy-uridine triphosphate biotin nick end labeling method, on gastric carcinoma lesions based on the endoscopic findings before administration in the biopsy and resected tissues. Expressions of p53, Bcl-2, Bax gene and proliferating cell nuclear antigen (PCNA) were also examined by immunohistochemical staining. On preoperative biopsy, p53 point mutation was observed in 14 of the 42 tumors. The immunohistochemical staining status and point mutation of p53 gene (positive or negative) were identical in 32 of the 42 tumors (76.2%). The average AIs of the biopsy specimens were 1.58+/-1.26% on p53-negative staining (n=19) and 1.14+/-1.02% on p53-positive staining (n=23), a significant association was not recognized between p53 expression and AI. In the preoperative administration group, the PCNA labeling index was significantly higher in the biopsy specimens than in the resected tissues (43. 6+/-12.8% vs. 35.3+/-8.8%, p<0.01). In addition, postoperatively, the rate of AI was significantly more accelerated in p53-negative staining (n=6) than in p53-positive staining (n=8) (0.89+/-0. 65%right curved arrow 4.18+/-3.26%, p<0.05 vs. 1.20+/-0.60%right curved arrow 2.60+/-2.60%, NS). There was no significant correlation between AI and Bcl-2 or Bax staining. Immunohistochemical analysis of p53 and PCNA stainings in biopsy specimens appears to be a well-characterized indicator of sensitivity of chemotherapy in gastric carcinomas.

Apoptosis↗

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The time interval between primary colorectal carcinoma resection to occurrence of liver metastases is the most important factor for hepatic resection. Analysis of total course following primary resection of colorectal cancer.

The lack of any other effective treatment for colorectal liver metastases makes hepatic resection a primary treatment consideration. Between January 1980 and December 1996, 36 patients with metachronous liver metastases who underwent hepatic resection were reviewed. The age, sex, site of primary lesion, stage, size and number of hepatic metastases, and time interval between primary colorectal carcinoma resection to occurrence of liver metastases (disease-free interval, DFI) were documented. DFI was 569 days on average. Complete removal of primary colorectal cancer and metastatic liver tumour with histologically negative resection margins was accomplished in all cases. The 5 year survival rate following the first operation for primary colorectal cancer was 43.1%. The length of DFI influenced, independently, patients' prognoses based upon not only univariate but also multivariate survival analysis (P<0.01). We conclude that the DFI is the independent prognostic factor for metachronous liver metastases after curative resection of primary tumour.

Colorectal Neoplasms↗

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Flow cytometric analysis and immunohistochemical staining for the p53 protein and proliferating cell nuclear antigen in submucosal carcinoma of the esophagus.

BACKGROUND/AIMS: The aim of this study was to examine the role of p53 gene and tumor proliferating activity using anti-proliferating cell nuclear antigen (PCNA) in squamous cell carcinoma (SCC) of the esophagus with invasion restricted to the submucosa. Their DNA contents and microscopic histopathological aspects were also studied. METHODOLOGY: Thirty-four submucosal SCC were studied histopathologically including immunohistochemical and flow cytometric analysis. RESULTS: DNA diploid was observed in 15 (44.1%) and DNA aneuploid in 19 (55.9%) cases. DNA ploidy patterns were relatively closely correlated with survival. Staining for the p53 product was positive in 61.8% of all cases. The average PCNA labeling rate (LR) was 55.9 +/- 16.7%. The incidence of lymph node metastasis was relatively higher in DNA aneuploid and high PCNA LR (> or = 50%) groups. There was, however, no significant correlation between p53 protein expression and lymph node metastasis. CONCLUSIONS: Our study suggests that DNA aneuploid and high PCNA LR are unfavorable characteristics and that p53 expression may not have a prognostic value.

Aged↗

PubMedDate not supplied

Adenoma and tiny carcinoma in adenoma of the papilla of Vater--p53 and PCNA.

BACKGROUND/AIMS: Adenomas develop only rarely in the small bowel mucosa. We particularly tried to clarify the histologic change in atypia of ampullary adenomas which are not familial polyposis. METHODOLOGY: Four adenomas, 4 adenocarcinomas, and 4 normal mucosal regions of the ampulla of Vater were investigated in this study. All cases were characterized in paraffin sections for the presence of p53 protein using the anti-p53 monoclonal antibody (DO7, Dako Corp., Glostrup, Denmark) and proliferating cell nuclear antigen using the anti-PCNA antibody (PC 10, Dako A/S, Copenhagen, Denmark). To obtain the percentages (labeling index) of PCNA, a dual wavelength imaging microdensitometer (CAS 200, Elmhurst, IL) was used. RESULTS: Transition of adenoma into adenocarcinoma was recognized in 2 of 4 cases. Labeling index of PCNA was 12.2% in normal mucosa, 41.3% in adenomas, and 66.0% in adenocarcinoma, respectively. In 2 cases with carcinoma in adenoma, labeling index was higher in carcinomatous lesion than in adenomatous lesion. p53 Protein was positive in all cases of adenocarcinoma of the ampulla of Vater, and not in any case of normal mucosa or adenoma. CONCLUSIONS: The adenoma-carcinoma sequence was morphologically recognized especially in tiny carcinoma in adenoma of the papilla of Vater. Both p53 mutation and high proliferative activity play important roles for the histogenesis of invasive adenocarcinoma.

Adenocarcinoma↗

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Strategy for pancreatic endocrine tumors.

BACKGROUND/AIMS: The endocrine tumors of the pancreas are rare diseases and there is no established standard therapy for the liver metastasis of pancreatic endocrine tumors. In this study, the therapy for the pancreatic endocrine tumors was evaluated. METHODOLOGY: The endocrine pancreas tumors of 13 patients had been surgically treated. All primary tumors were completely resected. The liver metastasis was recognized in 4 patients. Partial resection of the liver was performed in 2 patients. Lipiodol-transcatheter arterial embolization was performed for synchronous unresectable liver metastases in the other 2 patients. RESULTS: The patients with no liver metastases survived without recurrence (max: 18.8 yr; mean follow-up: 9.2 yr). The patient with resected synchronous solitary liver metastasis died of recurrent multiple liver metastases 5 months after surgery. The other patient with the metachronous liver metastasis completely resected survived 13.9 years. In the 2 patients with unresectable numerous liver metastases, after lipiodol-transcatheter arterial embolization, tumor necrosis rate was more than 90% in both cases and serum gastrin level was normalized. CONCLUSIONS: Complete resection of liver metastasis is favorable, whereas lipiodol-transcatheter arterial embolization is effective for unresectable liver metastases from pancreatic endocrine tumors as palliation. Complete resection of the primary site is recommended even in the cases with unresectable numerous liver metastases.

Adult↗

PubMedDate not supplied

Evaluation of PCNA, p53, K-ras and LOH in endocrine pancreas tumors.

BACKGROUND/AIMS: The object of this study was to evaluate the characters of the endocrine pancreas tumors including proliferative activity, p53 mutation, K-ras mutation and microsatellite instability. METHODOLOGY: The 13 endocrine tumors of the pancreas were enrolled in this study. There were 8 hypervascular tumors and 4 normo- or hypovascular tumors. All cases were immunohistochemically characterized in paraffin sections for the presence of proliferating cell nuclear antigen and p53 protein. Mutation in K-ras at codon 12 was detected by the Mutant-allele-specific amplification system. Microsatellite instability was examined by using frozen tissues in the 2 cases. RESULTS: Proliferating cell nuclear antigen labeling index range was 0.00-0.62 (0.26 +/- 0.23). p53 was positive in 4/13 tumors. K-ras codon 12 mutation was not detected in any tumors. PCNA LI was significantly lower in hypervascular tumors (0.16 +/- 0.20) than normo- or hypovascular tumors (0.44 +/- 0.17) (P < 0.05). PCNA LI was significantly lower in the p53-positive tumors (0.48 +/- 0.17) than the p53-negative tumors (0.17 +/- 0.18) (P < 0.05). K-ras codon 12 mutation was not detected in any tumors. Loss of heterozygosity in 3p was detected in 1 tumor. CONCLUSIONS: Hypervascular endocrine pancreas tumors have low proliferative activity. p53 mutation influences proliferation as the late event of tumor progression.

Adenoma, Islet Cell↗

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Vascular integrin beta 3 and its relation to pulmonary metastasis of colorectal carcinoma.

Integrin alpha v-beta 3 is involved in tumor angiogenesis while the clinical significance of beta 3 integrin expression in colorectal cancer and lung metastases. Analysis was performed on 51 colorectal cancer patients (22 with subsequent lung metastasis and 29 without lung metastasis). Fifty-one primary tumors and 22 lung metastases were examined for immunohistochemical detection of integrin beta 3. We found that the antibody VNR 5 to integrin beta 3 prefentially stains the blood vessels of small caliber. Indeed, vascular integrin beta 3 index was significantly higher in tumors of patients with lung metastasis than in those without lung metastasis. In the patients with lung metastases, vascular integrin beta 3 index was significantly lower in lung metastases than in primary tumors. It was immunohistochemically proved that integrin beta 3 is an important vascular endothelial cell market for lung metastasis.

Adenocarcinoma↗

PubMedDate not supplied

p53 immunoreactivity in Barrett's metaplasia, dysplasia, and adenocarcinoma--a case report.

Barrett's esophagus is a condition in which the stratified squamous epithelium of the esophagus is replaced by a columnar epithelium with malignant potential. Mutations of the tumor-suppressor gene p53 have been implicated in the evolution of esophageal carcinomas. The aim of this study was to determine whether p53 immunoreactivity in Barrett's esophagus is a marker of neoplasia and, if so, when it occurs in the metaplasia-dysplasia-carcinoma sequence. We treated a patient with esophageal carcinoma arising from the Barrett's esophagus. Consecutive evidence existed for a metaplasia-dysplasia-carcinoma in the same specimen. Immunohistochemical staining with the monoclonal antibody was used to detect the intranuclear protein product of mutated p53. No p53 immunoreactivity was seen in specimen of Barrett's mucosa. p53 immunoreactivity was found only in specimen of dysplasia and carcinoma. Immunoreactivity occurs late in the metaplasia-dysplasia-carcinoma sequence, during the transition to high-grade dysplasia.

Adenocarcinoma↗

PubMedDate not supplied

Treatment of patients with gastric cancer and duodenal invasion.

We retrospectively examined clinicopathologic features of gastric cancer with duodenal invasion to clarify the effect of surgical treatment that include pancreaticoduodenectomy (PD). Among 2504 patients with gastric cancer, 69 (2.8%) who had gastric cancer and duodenal invasion resected by surgical treatment were investigated. The mode of the duodenal invasion was grouped into three categories: mucosal type, submucosal type, and nodal type. Mucosal type is invasion of the duodenal mucosal layer, submucosal type is invasion of the submucosal layer or deeper, and nodal type is invasion from nodal metastatic lesions around the pancreatic head. The 5-year survival rates of curative PD and curative gastrectomy were 37.3% and 33.8%, respectively. Despite the incidence of adjacent tissue infiltration and significantly higher duodenal invasion average length in cases with PD than in cases with gastrectomy, there was no significant difference in the survival curves. However, the prognoses of the cases with nodal-type invasion were significantly poorer, and all these patients died within 2 years, regardless of whether curative PD had been performed. Curative PD improves the prognosis of cases with long duodenal invasion or pancreas infiltration except for nodal-type duodenal invasion.

Chi-Square Distribution↗

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Comparison of coronary dilating effects of Ki1769, a new K channel opener of the pyridinecarboximidamide type, and nifedipine in anesthetized dogs.

The coronary dilating effect of a new type of K channel opener, N-cyano-N'-(2-phenethyl)-3-pyridinecarboximidamide (Ki1769), was examined in anesthetized dogs in comparison with that of nifedipine. Administration of Ki1769 (30 and 100 micrograms/kg, i.v.) and nifedipine (1 and 3 micrograms/kg, i.v.) produced a dose-dependent decrease of mean blood pressure with a concomitant increase in heart rate. Ki1769 and nifedipine dose-dependently increased coronary blood flow and aortic blood flow and decreased coronary vascular resistance and total peripheral vascular resistance. The percentage decrease of coronary vascular resistance was greater than that of total peripheral vascular resistance with Ki1769 and nifedipine, but Ki1769 showed a greater specificity in the decrease of coronary vascular resistance than nifedipine. Glibenclamide (5 mg/kg, i.v.) inhibited these hemodynamic effects of Ki1769 but did not affect those of nifedipine. These results suggest that the preferential effect of Ki1769 on the coronary vascular bed is greater than that of nifedipine. Such a profile of Ki1769 is based on its K channel-opening action.

Anesthesia↗

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Sex differences in clinicopathological features of peripheral T1 adenocarcinoma of the lung.

Clinicopathological features of surgically-treated peripheral T1 adenocarcinoma of the lung were compared between 30 females and 26 males, and the following sex differences were observed; 1) Females were younger than males, 2) There was a higher percentage of smokers among males, 3) The acinar histologic subtype was less frequently found in females, 4) Well differentiated tumors were more frequently found in females, 5) K-ras gene mutations were observed only in males, 6) Prognosis was slightly better in females. As to other factors such as N-factor, tumor ploidy or central fibrosis, there was no statistical difference between the two groups. Although we were not able to explain the causes for the above sex differences, it was speculated that smoking was mainly responsible for them.

Adenocarcinoma↗

PubMedDate not supplied

Effect of KRN2391, a novel vasodilator, on endothelin-1-induced contraction of porcine coronary artery: comparison with cromakalim, nitroglycerin and nifedipine.

The relaxant effects of KRN2391 (K channel opener and nitrate-like), cromakalim (K channel opener), nitroglycerin (nitrate-like) and nifedipine (Ca channel blocker) were investigated in porcine isolated coronary arteries contracted by endothelin-1 and KCl. KRN2391, nitroglycerin and cromakalim concentration-dependently inhibited the 10(-8) M endothelin-1-induced contraction, but less potently inhibited the 40 mM KCl-induced contraction. Nifedipine concentration-dependently inhibited the 40 mM KCl-induced contraction more strongly than the 10(-8) M endothelin-1-induced contraction. KRN2391 and nitroglycerin produced a complete relaxation of arteries contracted by endothelin-1 at its maximum effect. Cromakalim and nifedipine, both at 3 x 10(-5) M, produced 83.9% and 73.3% of the complete relaxation of the endothelin-1-induced contraction, respectively. In the 40 mM KCl-induced contraction, nifedipine produced a complete relaxation, but KRN2391, cromakalim and nitroglycerin, all at 3 x 10(-5) M, produced a relaxation of 62.7%, 27.1% and 79.4%, respectively. The combination of cromakalim and nitroglycerin relaxed the 10(-8) M endothelin-1- and 40 mM KCl-induced contractions in a concentration-dependent manner. The relaxant effect of this combination was greater against the endothelin-1-induced contraction than against the 40 mM KCl-induced contraction. The maximum relaxation of the combination of cromakalim (3 x 10(-5) M) and nitroglycerin (3 x 10(-6) M) was complete for the endothelin-1-induced contraction but a relaxation of 77.8% was obtained for the 40 mM KCl-induced contraction, i.e. the relaxant effects using this combination were greater than those by cromakalim (3 x 10(-5) M) alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

No development of tolerance to the hypotensive effect of KRN2391, a novel vasodilator containing a nitrate moiety.

The present studies were performed to examine whether tolerance develops to the hypotensive effects of KRN2391, N-cyano-N'-(2-nitroxyethyl)-3-pyridinecarboximidamide monomethanesulfonate. Rats were administered KRN2391 (0.3 or 1 mg/kg, s.c.) or nitroglycerin (10 mg/kg, s.c.) three times a day for 1 to 8 days and blood pressure was then measured under anesthesia. Chronic pretreatment with nitroglycerin attenuated the decrease in blood pressure induced by i.v. nitroglycerin but not that by i.v. KRN2391. Chronic pretreatment with KRN2391 (0.3 or 1 mg/kg, s.c.) had no effect on the decreases in blood pressure induced by i.v. nitroglycerin or i.v. KRN2391. It can be concluded that, in this rat model, no tolerance develops to the hypotensive effects of KRN2391.

Animals↗

PubMedDate not supplied

Prognostic factors in resected hepatocellular carcinomas and therapeutic value of transcatheter arterial embolization for recurrences.

The authors summarize the results of patients who had hepatectomy for hepatocellular carcinoma (HCC) over a 16-year period. Survival rates for 52 patients with HCC classified according to the Liver Cancer Study Group of Japan were calculated according to various clinicopathological variables. A univariable analysis revealed that alpha-fetoprotein > or =2000 ng/ml, portal involvement, tumor size > or =3.1 cm, and noncurative resection were associated with unfavorable outcomes, while neither the number of tumors nor underlying cirrhosis was associated with such outcomes. Furthermore, some of the patients with recurrence survived long after transcatheter arterial embolization (TAE) for recurrent tumors. Early detection as well as TAE for recurrent HCCs is necessary to improve long-term survival.

Adult↗