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Biomedical subjects

W Yasui

Publications and source records attributed to W Yasui.

At least 199 records · Page 11Linked to original sources
PubMed1986

Gut endocrine cells in rat stomach carcinoma induced by N-methyl-N'-nitro-N-nitrosoguanidine.

Gut endocrine cells in a total of 18 gastric adenocarcinomas in inbred Wistar rats induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and gastrin or serotonin, were examined histologically, ultrastructurally, and immunohistochemically for gastrin, somatostatin, calcitonin, glicentin, and serotonin. A large number of argyrophil cells were observed in 17 tumors (94.4%) and 14 tumors (77.8%) had argentaffin cells. Immunohistochemically, C-terminal fragment of gastrin (G17) immunoreactivity was observed in 15 (82.2%) out of the 18 tumors, but 3 G17-positive tumors had no G 34 immunoreactive cells in rats treated with MNNG plus gastrin. Serotonin immunoreactivity was detected in 14 tumors (77.8%). Somatostatin immunoreactivity was detected in 7 of the 11 tumors (63.6%) in rats treated with MNNG plus gastrin whereas no tumor in rats treated with MNNG plus serotonin had somatostatin, the difference of the incidence being significant (P less than 0.05). One endocrine cell carcinoma which consisted mainly of serotonin-producing cells was observed in a rat treated with MNNG plus serotonin. Calcitonin and glicentin immunoreactivity was not demonstrated in any tumors. Ultrastructurally, three types of endocrine granule were found in the tumor cells. These data suggest that hormonal environment in stomach carcinogenesis may influence the expression of endocrine cells within the tumors.

Adenocarcinoma↗
PubMed1986

Light and electron microscopic observations of the white pulp of the dog spleen during hemorrhagic shock.

Structural changes of the white pulp of the spleen were investigated in dogs subjected to hemorrhagic shock. At 1 h after hemorrhage (early impending stage), hydropic changes of the germinal center cells were observed by electron microscopy, while no remarkable change could be found by light microscopy. At 2 h after hemorrhage (end of impending stage), tangible bodies increased in number in the germinal center as a result of destruction of germinal center cells. In addition, tangible bodies appeared also in the perifollicular zone, while there were few tangible bodies in the follicular area. At the end of critical stage (3 h after hemorrhage), destruction of cells was remarkable not only in the germinal center and perifollicular zone, but also in the follicular area. Tangible bodies and tangible body macrophages were abundant in germinal center, follicular area and perifollicular zone. Moreover, acellular areas frequently appeared in the follicular area which was composed predominantly of small lymphocytes. At the terminal stage of normovolemic shock, the cells of white pulp including perifollicular zones were markedly decreased. Hemorrhages were frequently recognized in the germinal center and follicular area.

Animals↗
PubMed1986

Human epidermal growth factor in gastric carcinoma as a biologic marker of high malignancy.

The presence of human epidermal growth factor (hEGF) was studied in a total of 210 gastric carcinomas comprising 52 early carcinomas, 113 advanced carcinomas and 45 scirrhous carcinomas. An immunohistochemical study revealed no hEGF-immunoreactivity in early gastric carcinomas, while hEGF-positive tumor cells were detected in 24 (21.2%) of the 113 advanced carcinomas and in 15 (33.3%) of the 45 scirrhous carcinomas. The incidence of hEGF-immunoreactivity in well-differentiated adenocarcinomas was significantly higher than that in poorly differentiated adenocarcinomas (P less than 0.05). Moreover, hEGF-immunoreactive tumor cells were observed in 13 (30.4%) of the 42 scirrhous poorly differentiated adenocarcinomas, the incidence being significantly higher than that in non-scirrhous poorly differentiated adenocarcinomas (P less than 0.05). The average hEGF content in the tumor tissue estimated by radioimmunoassay was 3.77 +/- 0.61 (mean +/- SE) ng/g wet weight in immunohistochemical hEGF-positive tumors and 2.19 +/- 0.18 ng/g wet weight in hEGF-negative tumors, the difference being significant (P less than 0.05). Patients with hEGF-positive carcinomas (excluding scirrhous carcinomas) had much worse prognosis than those with hEGF-negative carcinomas. These results suggest that EGF produced by tumor cells plays an important role in the invasive growth and productive fibrosis of gastric carcinoma and also serves as a biologic marker of high malignancy in patients with gastric cancers.

Adenocarcinoma↗
PubMed1986

Cholecystokinin inhibition of tumor growth and gastrin-stimulated cyclic adenosine 3':5'-monophosphate metabolism in human gastric carcinoma in nude mice.

This study deals with the effect of four types of COOH-terminal cholecystokinin (CCK) fragments on the growth of xenotransplantable human gastric cancer (SC-6-JCK, a poorly differentiated adenocarcinoma) whose growth has been promoted by pentagastrin. The growth of the tumor was inhibited using daily s.c. injections of CCK-octapeptide (CCK-8) and glutaryl-CCK-8 at a dose of 500 micrograms/kg body weight. After 30 days of treatment with CCK-8 or glutaryl-CCK-8, a significant decrease was observed in the tumor weight (P less than 0.05) and the tumor size P less than 0.01) in comparison with those of the control. But treatment with CCK-12 and pyroglutamyl-CCK-8 did not produce inhibition of tumor growth. Furthermore the correlation between the effect of CCK-8 on the normal rise in tumor cyclic adenosine 3':5'-monophosphate (cAMP) levels caused by pentagastrin injection and tumor growth was studied. The increase of cAMP by a single i.p. injection of pentagastrin at a dose of 20 micrograms/mouse was significantly inhibited by pretreatment with CCK-8 at concentrations equimolar to pentagastrin (P less than 0.05), while cAMP in the tumor was slightly elevated by a single i.p. injection of CCK-8 alone. Also in the in vitro study, CCK-8 inhibited the increase of cAMP and the activation of cAMP-dependent protein kinase which was stimulated by pentagastrin. These results suggest that proliferation of gastrin-dependent human gastric cancers may be suppressed by CCK in competition with gastrin.

Adenocarcinoma↗
PubMed1986

Ha-ras oncogene product in human gastric carcinoma: correlation with invasiveness, metastasis or prognosis.

c-Ha-ras oncogene product in human gastric carcinomas was examined by Western blotting and immunohistochemistry using anti-Ha-ras p21 antibody. In Western blotting, high levels of c-Ha-ras p21s were found in gastric carcinomas. Immunohistochemically, c-Ha-ras p21 was detected in 3 (11.1%) of 27 early carcinomas and in 63 (43.8%) of 144 advanced carcinomas. In advanced carcinomas, c-Ha-ras p21-immunoreactivity was correlated with the depth of tumor invasion and was stronger in metastatic tumors than in primary tumors. Patients with c-Ha-ras p21-positive carcinomas had a significantly worse prognosis than those with p21-negative carcinomas.

Amino Acid Sequence↗
PubMed1985

Growth-promoting effect of gastrin on human gastric carcinoma cell line TMK-1.

A human gastric carcinoma cell line TMK-1 was established in vitro by the soft agar method from SC-6-JCK, a poorly differentiated adenocarcinoma xenotransplanted in nude mice. TMK-1 cells had a doubling time of approximately 35 hr and showed carcinoembryonic antigen (CEA), alpha 1-antitrypsin and secretory component immunoreactivity. Ultrastructurally, the tumor cells were characterized by numerous mitochondria, tubulovesicles and intracytoplasmic canaliculi filled with abundant microvilli. The growth of TMK-1 cells was promoted by 10nM human gastrin (G-17), 2 microM tetragastrin or 2 microM pentagastrin, among which human gastrin showed the most effective growth promotion. Moreover, incorporation of [3H]thymidine into TMK-1 cells was stimulated by gastrin in a dose-dependent manner. The content of cyclic adenosine 3',5'-monophosphate (cAMP) in TMK-1 cells was increased by gastrin treatment but decreased to the control level within 10 min. cAMP-dependent protein kinase was also activated by gastrin administration.

Carcinoma↗
PubMed1985

Calcium-activated, phospholipid-dependent protein kinase in human gastric mucosa and carcinoma.

Ca2+-activated, phospholipid-dependent protein kinase (protein kinase C) activities in human gastric mucosa and carcinoma were examined. The bulk of protein kinase C activity was associated with the cytosol in both gastric mucosa and carcinoma. Protein kinase C activity in the soluble fraction in human gastric carcinoma was significantly higher than that in nonneoplastic gastric mucosa (P less than 0.05), the values being 357.7 and 215.3 units/g protein, respectively. On the other hand, cAMP-dependent protein kinase (protein kinase A) activity was decreased slightly in gastric carcinomas. The ratios of protein kinase C to protein kinase A in human gastric carcinoma and nonneoplastic mucosa were 0.849 and 0.435, respectively, the difference being significant (P less than 0.01). In DEAE-cellulose column chromatography, the elution profiles of protein kinases from gastric carcinomas were the same as those from gastric mucosas except that a larger peak of protein kinase C was found. It seems probable that increased protein kinase C activity plays an important role in the growth of human gastric carcinoma as a signal transducer.

Carcinoma↗
PubMed1985

Type I and II cyclic adenosine 3':5'-monophosphate-dependent protein kinase in human gastric mucosa and carcinomas.

Cyclic adenosine 3':5'-monophosphate (cAMP)-dependent and cAMP-independent protein kinase activity and the isoenzyme pattern of cAMP-dependent protein kinase were compared in tissues from human nonneoplastic gastric mucosa, 11 human gastric carcinomas, and 2 xenotransplantable human gastric carcinomas (SC-6-JCK and St-15). No difference in total protein kinase activity could be observed between nonneoplastic gastric mucosa and gastric carcinomas. According to diethylaminoethyl cellulose column chromatography, the isoenzyme pattern of the nonneoplastic gastric mucosa was the same in both the gastric fundus and the antrum, and the activity ratio of type II to type I was 5.01. In gastric carcinomas, the elevation of type I was detected independently of the histological type. In xenotransplantable human gastric carcinomas in nude mice, type I isoenzyme was significantly elevated. The activity ratio of type II to type I was 1.70 in SC-6-JCK carcinomas and 1.81 in St-15 carcinomas, respectively. These results suggest that type I cAMP-dependent protein kinase activity in the stomach may be a biochemical marker for malignant transformation and transplantability of gastric tumors.

Chromatography, DEAE-Cellulose↗
PubMed1985

Effect of gastrin on gastric mucosal cyclic adenosine 3':5'-monophosphate-dependent protein kinase activity in rat stomach carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine.

This was a study of the effects of gastrin on gastric mucosal cyclic-adenosine 3':5'-monophosphate (cAMP)-dependent protein kinase activity and DNA synthesis in rat stomach carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in order to clarify the mechanism of the enhanced effect of gastrin on the early stage of stomach carcinogenesis. Inbred Basel-Wistar rats received MNNG in drinking water (50 micrograms/ml for 32 weeks) and were treated with s.c. injections of pentagastrin (300 micrograms/kg twice daily for 4 weeks) beginning with the fourth and eighth weeks after the initiation of MNNG treatment. The incidence of gastric adenocarcinoma in fourth-week gastrin-treated rats and of gastric carcinoid in eighth-week gastrin-treated rats was higher than that in rats treated with MNNG alone. The former tumors developed in the antrum and most of the latter tumors in the fundus. In the early stage of carcinogenesis the labeling index [( 3H]thymidine-labeled nuclei/one gland) in both the antrum and fundus was the same in MNNG-plus-gastrin-treated groups and in the MNNG-only-treated group. With regard to the distribution of cAMP-dependent protein kinase isoenzyme in fourth-week gastrin-treated rats, the proportion of type I cAMP-dependent protein kinase significantly increased in the antrum during the eighth week after the initiation of MNNG treatment (P less than 0.01). The increased type I activity in the antrum of the gastrin-treated rats agreed with the high incidence of gastric adenocarcinoma in the antrum. Type I isoenzyme clearly increased in gastric adenocarcinoma. These results suggest that type I cAMP-dependent protein kinase can play an important role in the enhanced effect of gastrin on rat stomach carcinogenesis induced by MNNG.

Adenocarcinoma↗
PubMed1984

Effects of gastrin on tumor growth and cyclic nucleotide metabolism in xenotransplantable human gastric and colonic carcinomas in nude mice.

This study deals with the growth effect of gastrin on two xenotransplantable human gastric carcinomas (SC-6-JCK, poorly differentiated adenocarcinoma; and St-15, mucinous adenocarcinoma) and on one colonic carcinoma (Co-3, well-differentiated adenocarcinoma). In SC-6-JCK, the treatment with s.c. injection of pentagastrin at a dose of 10 micrograms/mouse once daily for 25 days promoted the growth of the tumor transplanted in nude mice, but gastrin had no effect at all on St-15 and Co-3. In SC-6-JCK, the weight, size, and labeling index of [3H]thymidine of the tumor were significantly increased in comparison with those of the control (p less than 0.05). In SC-6-JCK, cyclic adenosine 3':5'-monophosphate (cAMP) in the tumor was increased by a single i.p. injection of pentagastrin at a dose of 20 micrograms/mouse in nude mice, but such an increase was not observed in St-15 and Co-3. Cyclic guanosine 3':5'-monophosphate in SC-6-JCK was slightly increased by gastrin treatment but was not affected in the other tumors. In SC-6-JCK, at 30 min after gastrin treatment when cAMP showed a maximum increase, the activity ratio of cAMP-dependent protein kinase in the tumor was also elevated. In vitro also, gastrin stimulated cAMP production and cAMP-dependent protein kinase activation. The data suggest that some human gastric carcinomas may have receptor for gastrin.

Adenocarcinoma↗
PubMed1984

Secretory component and immunoglobulin in human gastric carcinoma: an immunohistochemical study.

The occurrence of secretory component (SC), IgA, IgG and IgM within tumor cells was immunohistochemically examined in a total of 101 gastric carcinomas comprising 50 early cancers and 51 advanced cancers. In advanced cancers, the frequency of SC was significantly higher in well-differentiated adenocarcinoma than in poorly differentiated adenocarcinoma. The frequency of IgA did not differ with stage of cancer, but the frequencies of IgG and IgM were significantly higher in advanced cancer than in early cancer. The immunoglobulin-producing plasma cells in the stroma of advanced cancer were chiefly IgG, followed by IgA and IgM producers. The intensity of IgA plasma cell infiltration correlated with presence of IgA in tumor cells. No correlation was noted between serum immunoglobulin value and immunoglobulin in tumor cells. The survival rate indicated a tendency for IgG-containing advanced cancers which were infiltrated with many IgG plasma cells to have a better prognosis.

Adenocarcinoma↗
PubMedDate not supplied

Reduced expression of cyclin-dependent kinase inhibitor p27(Kip1) in oral malignant tumors.

p27(Kip1), a cyclin-dependent kinase (CDK) inhibitor, blocks progression from the G(1) to S phase by binding cyclin E-CDK2 and inhibiting their activities. We studied the expression of p27 in oral tumors by immunohistochemistry to determine whether lack of p27 plays a role in the development and progression of oral cancer. Reduced expression of p27 was detected in 86% of the squamous cell carcinomas and 95% of the mucoepidermoid carcinomas, respectively, while p27 expression was well preserved in the pleomorphic adenomas. The expression of p27 showed an inverse correlation with the expression of cyclin E in the squamous cell carcinomas and mucoepidermoid carcinomas. However, there was no relationship between clinicopathological parameters and p27 expression. These results suggest that the reduction of p27 protein may confer the development of oral squamous cell carcinoma and mucoepidermoid carcinoma partly through the increased expression of cyclin E.

Adenoma, Pleomorphic↗
PubMedDate not supplied

Expression of cell-cycle-regulating transcription factor E2F-1 in colorectal carcinomas.

The expression of E2F-1 in human colorectal carcinomas was examined immunohistochemically, and the correlation of E2F-1 expression with clinicopathological findings and with the expression of p27(Kip1) was analyzed to elucidate the role of E2F-1 in the development and progression of colorectal carcinomas. In nonneoplastic mucosa, a small number of epithelial cells in the proliferative zone were weakly positive for E2F-1. Weak expression of E2F-1 was detected in many adenoma cells. Most of the colorectal carcinomas expressed E2F-1 at various levels, and strong expression of E2F-1 was detected in 56% (49/88) of the cases. There was no correlation between the expression of E2F-1 and any clinicopathological parameters such as tumor stage, depth of tumor invasion and lymph node metastasis. Reduced expression of p27(Kip1) was confirmed to be significantly correlated with deep tumor invasion and presence of metastasis. No correlation was evident between overexpression of E2F-1 and reduced p27(Kip1) expression.

Adenocarcinoma↗
PubMedDate not supplied

nm23 protein expression in renal cell tumors: the role of the cell type.

This study investigated nm23 protein expression in renal cell carcinomas to determine the relationship between nm23 protein expression and grade, stage, prognosis and the cell type. 89 cases were examined by immunohistochemistry. Tubular epithelia were homogeneously stained. Cytoplasmic nm23 protein levels were reduced in renal cell carcinoma. nm23 protein levels persisted in oncocytomas, which are accepted to be benign. Cytoplasmic nm23 staining intensity did not show any correlation with stage and grade of tumor nor prognosis. Reduction in nm23 protein levels may have a role during renal cell carcinoma pathogenesis but not in progression or metastasis suppression.

Adult↗
PubMedDate not supplied

Expression of p27Kip1, cyclin E and E2F-1 in primary and metastatic tumors of gastric carcinoma.

The cell cycle is controlled by positive and negative regulators. Gene abnormalities and aberrant expressions of various cyclins/CDKs and CDK inhibitors may play a pivotal role in stomach carcinogenesis. To clarify the role of cyclin E, CDK inhibitor p27Kip1 and their target molecule, E2F-1 in tumor metastasis, we examined immunohistochemically the expression of cyclin E, p27Kip1 and E2F-1 in 23 gastric carcinomas and metastatic tumors of the lymph node. Most of gastric carcinomas with lymph node metastasis showed reduced p27Kip1 expression. p27Kip1 was negative in 39% (9/23) of primary tumors, while it was so in 52% (12/23) of lymph node metastases. By comparison of p27Kip1 expression in primary and metastatic tumors in individual cases, metastatic tumor cells in the lymph nodes were expressed at weaker levels than in those in primary tumors in 43% (10/23) of the cases. On the other hand, over 70% (17/23) and 50% (12/23) of the cases expressed cyclin E and E2F-1 at nearly the same levels in both primary tumor and lymph node metastasis, respectively. These results suggest that tumor cells with reduced p27Kip1 expression may selectively metastasize to lymph node or distant organs.

Carrier Proteins↗
PubMedDate not supplied

No mutations of the Bub1 gene in human gastric carcinomas.

Chromosomal instability in colorectal cancers is associated with functional loss of a mitotic check point partly due to mutations of the Bub1, one of the mitotic check point genes. However, mutation of coding sequences of human Bub1 gene has not been fully elucidated in gastric carcinomas. We performed sequencing analysis on reverse transcriptase-polymerase chain reaction (RT-PCR) product of the Bub1 cDNA (entire coding sequence) from 5 human gastric carcinomas as well as on genomic PCR products of Bub1 kinase domain from 7 gastric carcinoma tissues. Although sequencing analysis of the Bub1 cDNA revealed several point mutations in 2 gastric carcinoma cases, we could not confirm the mutations by analyzing genomic DNA. Furthermore, genomic DNA sequencing revealed no mutations in the kinase domain of the Bub1 gene in any gastric carcinoma examined. These results suggest that mutational inactivation of the Bub1 gene might not play a key role in human stomach carcinogenesis.

Adenocarcinoma↗
PubMedDate not supplied

DNA methylation status of hMLH1, p16(INK4a), and CDH1 is not associated with mRNA expression levels of DNA methyltransferase and DNA demethylase in gastric carcinomas.

DNA methyltransferase and DNA demethylase are enzymes potentially affecting promoter methylation status. We examined levels of DNA methyltransferase (DNMT1, DNMT3a, DNMT3b) and DNA demethylase (MBD2) mRNA expression by semi-quantitative RT-PCR. In addition, we examined promoter methylation status of hMLH1, p16(INK4a), and CDH1 by methylation-specific PCR since all three of these genes are reported to be hypermethylated in gastric carcinoma. MBD2 appeared to be down-regulated in neoplasms. The levels of DNMT1, DNMT3a, DNMT3b, and MBD2 mRNA expression were not associated with either tumor stage or histologic type. Promoter hypermethylation of hMLH1, p16(INK4a), and CDH1 was detected in 5/20 (25%), 8/20 (40%) and 8/20 (40%) of gastric carcinomas, respectively. There was no clear relation between DNA methylation status of hMLH1, p16(INK4a), and CDH1 and the mRNA expression levels of DNMT1, DNMT3a, DNMT3b or MBD2. We divided the examined cases into two groups according to the number of hypermethylated genes. Cases with more than two hypermethylated genes comprised a hypermethylation group, and cases with no hypermethylation comprised a non-hypermethylation group. We found no group association for levels of DNMT1, DNMT3a, DNMT3b, and MBD2 mRNA expression. Our results suggest that the mRNA expression levels for pro-methylating (DNMT1, DNMT3a, DNMT3b) and anti-methylating (MBD2) enzymes is not a critical determinate of tumor-specific promoter hypermethylation of hMLH1, p(16INK4a), or CDH1 in gastric carcinoma.

Adaptor Proteins, Signal Transducing↗