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Biomedical subjects

W Yasui

Publications and source records attributed to W Yasui.

At least 163 records · Page 9Linked to original sources
PubMed1992

Expression of transforming growth factor alpha in human tissues: immunohistochemical study and northern blot analysis.

The expression of transforming growth factor alpha (TGF-alpha) was examined in various human tissues and the fetus, using immunohistochemistry and Northern blot analysis. TGF-alpha immunoreactivity was detected mainly in the epithelial cells of the digestive tract, liver, pancreas, kidney, thyroid, adrenal, skin, mammary gland and genital organs. In the digestive tract, epithelial cells with regenerative change or hyperplastic change showed strong immunoreactivity to TGF-alpha. Peripheral nerve, vessels, megakaryocytes and macrophages in the lung and spleen were also positive for TGF-alpha. By Northern blot analysis the expression of TGF-alpha mRNA was confirmed in the digestive tract, salivary gland, thyroid, kidney and mammary gland. In the human fetus, the nerve tissues, liver, adrenal and kidney were positive for TGF-alpha. Strong immunoreactivity to TGF-alpha was observed in the hepatocytes of the fetus. These findings indicate that TGF-alpha is produced by a variety of non-neoplastic cells in both adult and fetal tissues.

Adrenal Glands↗
PubMed1992

Tyrosine kinase activity of epidermal growth factor receptor in human gastric carcinomas.

We examined tyrosine kinase activity of epidermal growth factor (EGF) receptor in a total of 34 human gastric carcinomas as well as in non-neoplastic gastric mucosa from the same patients. EGF receptor kinase activity of the carcinoma tissues and the non-neoplastic mucosa were 1.28 +/- 1.00 (Mean +/- S.E.) and 0.16 +/- 0.04 respectively, if the EGF receptor kinase activity of human placenta is 10. Twenty-one (62%) carcinoma tissues showed higher EGF receptor kinase activity than corresponding non-neoplastic mucosa, while in 6 cases (18%) the kinase activity was higher in the non-neoplastic mucosa than in the tumor tissues. No obvious correlation was observed between the increased kinase activity in the tumors and histological type or tumor staging. One tumor showed extremely high receptor kinase activity with ERBB gene amplification. This tumor showed strong immunoreactivity to EGF itself.

ErbB Receptors↗
PubMed1992

A serine protease-inhibitory benzamidine derivative inhibits the growth of human colon carcinoma cells.

The inhibitory effect of a serine protease-inhibiting tetra-benzamidine derivative, TAPP-Br, on the cell growth of 8 human colon carcinoma cell lines was examined and the mechanism of the inhibition was analyzed. TAPP-Br inhibited the cell growth of all the colon carcinoma cell lines, and this effect was irreversible. The expression of mRNAs for nuclear oncogenes such as MYC, FOS and JUN was decreased by TAPP-Br after treatment for 3 h and the effect continued for 48 h. mRNA expression of epidermal growth factor receptor, transforming growth factor-beta and type IV collagenase was suppressed at 48 h after the initiation of TAPP-Br treatment, suggesting an indirect action of TAPP-Br. TAPP-Br decreased protein kinase C activity in the particulate fraction, whereas it increased the enzyme activity in the soluble fraction. These findings overall suggest that the serine protease inhibitor, TAPP-Br, might inhibit the cell growth of colon carcinoma cell lines through suppressing the expression of genes whose promoter contains a 12-O-tetradecanoylphorbol-13-acetate-responsive element or serum-responsive element.

Antineoplastic Agents↗
PubMed1992

Reduced levels of transforming growth factor-beta type I receptor in human gastric carcinomas.

The expressions of transforming growth factor beta (TGF-beta) and its receptor and TGF-beta inhibitory element (TIE)-binding protein were examined on human gastric carcinomas by Northern blot hybridization, immunohistochemistry, affinity labeling and gel retardation analysis. TGF-beta mRNA was expressed in tumor and normal tissues at various levels. Immunohistochemically, TGF-beta expression was confirmed to be present within tumor cells. Out of the 17 human gastric carcinoma tissues, 14 (82%) showed a reduction in the level of type I receptor (65 kDa) for TGF-beta when compared to corresponding normal mucosas. Interestingly, in seven of the 14 tumors the level of TIE-binding protein in the tumor tissue was lower than that in normal mucosa. Human gastric carcinoma cell line TMK-1, whose growth was inhibited by TGF-beta, had only type I receptor for TGF-beta and showed a high level of TIE-binding protein. Conversely, MKN-1, a TGF-beta-resistant cell line, exhibited an extremely low level of TGF-beta receptor and had no TIE-binding protein. These results overall indicate that although human gastric carcinoma cells produced TGF-beta, they showed a reduction in TGF-beta type I receptor and a low level of TIE-binding protein, resulting in escape from growth inhibition by TGF-beta.

Aged↗
PubMed1992

[New prognostic factors in human gastric carcinomas].

Correlation between the expression of growth factor/receptor systems or the alterations of tumor suppressor genes and biological malignancy of gastric cancer was described. Overexpression of many growth factors/receptors, such as EGF, TGF alpha, EGF receptor and ERBB2, and reduction of type I receptor for TGF beta may be linked with new prognostic factors of gastric carcinomas. The expression of cripto, a novel gene of EGF family, shows a tendency to correlate with tumor staging of well differentiated gastric adenocarcinomas. p53 gene abnormalities take place in 60% of gastric carcinomas including early stage carcinoma. Loss of heterozygosity on chromosomes 1q, 7p and 7q is frequently observed in advanced gastric carcinomas of well differentiated type. Molecules which regulate tumor invasion and metastasis such as nm23, tissue inhibitor of metalloproteinase (TIMP) and endogenous galactoside-binding lectin may provide for prognostic factors of gastric cancer.

Alleles↗
PubMed1991

Effects of tyrosine kinase inhibitor, erbstatin, on cell growth and growth-factor/receptor gene expression in human gastric carcinoma cells.

The effect of tyrosine kinase inhibitor, erbstatin, on cell growth and mRNA expression of growth-factor/receptor system was examined in 6 human gastric-carcinoma cell lines. Erbstatin inhibited both EGF-induced and serum-stimulated cell growth of all 6 cell lines (TMK-1, MKN-1, -7, -28, -45, -74) in a dose-dependent manner. 3H-thymidine incorporation by TMK-1 cells was also suppressed by erbstatin. Erbstatin inhibited protein kinase activity of EGF receptor, p185ERBB2 and pp60c-src in TMK-1 cells. The expression of mRNA of EGF receptor gene and ERBB-2 by TMK-1 cells was not changed by erbstatin treatment, whereas that of c-src was slightly decreased. Interestingly, erbstatin decreased membrane-bound TGF-alpha precursor as measured by anti-TGF-alpha antibody-binding assay, although mRNA expression for TGF-alpha was not altered by erbstatin. Our findings suggest that erbstatin may act as a growth inhibitor for human gastric-carcinoma cells and may not only inhibit tyrosine kinase activities but also negatively modulate the post-transcriptional step of TGF-alpha expression.

Cell Division↗
PubMed1991

Expression of epidermal growth factor in human tissues. Immunohistochemical and biochemical analysis.

The expression of epidermal growth factor (EGF) was examined on various human tissues by radioimmunoassay, immunohistochemistry and Northern blot analysis. Immunoreactive EGF was found in most of the human tissues by radioimmunoassay at various levels. Large quantities of EGF were detected in the kidney and thyroid gland. Immunohistochemically, EGF immunoreactivity was detected mainly in the epithelial cells of the lung, stomach, duodenum, pancreas, kidney, pituitary gland, thyroid gland, mammary gland, ovary, uterus and placenta. Weakly EGF-positive cells were also found in the adrenal gland. The results of EGF-immunostaining were not always consistent with the data from radioimmunoassay. We consider that the amount of EGF measured by radioimmunoassay reflects the density of EGF-positive cells in the tissues and the concentration of EGF in individual EGF-positive cells. Furthermore, EGF mRNA was expressed in the salivary gland, thyroid gland, mammary gland and kidney. It is thus evident that EGF is produced by a variety of human tissues. The kidney expressed exceptionally high levels of EGF mRNA which was about one-tenth of the expression in mouse submandibular gland, suggesting that most of EGF in the urine is produced and secreted by the epithelial cells of renal tubules.

Epidermal Growth Factor↗
PubMed1991

Expression of basic fibroblast growth factor in human gastric carcinomas.

The expression of mRNA for the basic fibroblast growth factor (FGF) gene was examined in seven human gastric carcinoma cell lines and in tissue from 29 gastric carcinomas together with the adjacent normal mucosa. Among the seven gastric carcinoma cell lines, the MKN45 cell line expressed mRNA for the basic FGF gene. Basic FGF protein production was confirmed by flow cytometric analysis and immunohistochemistry. Among the surgical specimens, 16 (55%) of 29 gastric carcinomas showed higher levels of basic FGF mRNA than the normal mucosa. Interestingly, in scirrhous gastric carcinomas characterized by their fibrous stroma and rapid growth, 9 (69%) of 13, samples examined revealed higher levels of basic FGF mRNA than normal mucosa, whereas only 3 (33%) of the 9 well differentiated adenocarcinomas studied produced similar results. Immunohistochemically, basic FGF protein was localized in tumor cells. These results suggest that basic FGF produced by tumor cells may play an important role in producing fibrosis and angiogenesis in gastric carcinomas.

Adult↗
PubMed1991

Inhibitory effect of 8-chloro-cyclic adenosine 3',5'-monophosphate on cell growth of gastric carcinoma cell lines.

A cAMP analogue, 8-chloro-cAMP (8-Cl-cAMP), selectively binds to site 1 receptor of type II regulatory subunit (RII) of cAMP-dependent protein kinase. The effects of 8-Cl-cAMP on human gastric carcinoma cell lines were studied. Twenty microM 8-Cl-cAMP clearly inhibited cell growth in six cell lines (TMK-1, KATO-III, MKN-7, -28, -45, and -74) but not in MKN-1. Cell population in the G1 phase was increased in KATO III cells, which were more responsive to 8-Cl-cAMP, while cell cycle progression in TMK-1 and MKN-1 cells was apparently not influenced by 8-Cl-cAMP. The various changes induced by 8-Cl-cAMP were further analyzed in TMK-1 cells. Decrease of type I regulatory subunit (RI) of cAMP-dependent protein kinase and translocation of RII from cytosol to nucleus were induced by 8-Cl-cAMP treatment. 8-Cl-cAMP increased the level of cAMP-response element (CRE) binding protein in addition to inducing FOS mRNA, whose promoter contains CRE. 8-Cl-cAMP decreased the expression of mRNA for transforming growth factor-alpha (TGF-alpha), while the expression of epidermal growth factor receptor was not changed. Expression of HRAS and MYC mRNAs was slightly increased, whereas the amounts of HRAS and MYC proteins remained unchanged. Our results overall suggest that 8-Cl-cAMP might be a useful tool for antitumor therapy of gastric cancers and that cell growth inhibition by 8-Cl-cAMP might account for the decrease of TGF-alpha expression by tumor cells.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1991

Expression of cripto, a novel gene of the epidermal growth factor family, in human gastrointestinal carcinomas.

The expression of mRNA for cripto gene, a novel transforming gene of the epidermal growth factor family, was examined in 20 alimentary tract carcinoma cell lines, 60 surgically resected tumor tissues and their adjacent normal mucosas. Although the cripto mRNA was not detected in esophageal carcinomas or in normal mucosas, it was detected in gastric and colorectal carcinomas. In gastric carcinomas, 2.2 kb cripto mRNA was detected in one cell line, all the gastric carcinoma tissues and their adjacent normal mucosas. Of 23 gastric tumor tissues 8 (34.8%) exhibited a higher mRNA level than normal gastric mucosas. cripto mRNA was detected in 2 out of 6 colorectal carcinoma cell lines. Interestingly, 18 (81.8%) out of 22 colorectal carcinoma specimens expressed a higher level of cripto mRNA than that in normal mucosas. The level of the expression was higher than that in gastric carcinoma tissues. The expression was also correlated to tumor stage of colorectal carcinomas.

Adult↗
PubMed1991

Myxoid leiomyosarcoma of the stomach: a case report.

A case of myxoid leiomyosarcoma of the stomach which developed in a 53-year-old man is reported. The tumor was localized mainly in the greater omentum and was directly connected to the muscle layer of the stomach. No direct invasion to adjacent organs, peritoneal disseminations or distant metastases were noted. Histologically, the tumor prominently comprised a myxomatous lesion with a cellular area portion. The tumor cells had a bipolar or multipolar shape with oval or elongated nuclei, and were scattered in the myxoid stroma which was rich in hyaluronic acid. The cellular area showed a fascicular tumor cell arrangement and also contained pleomorphic tumor cells with abundant mitoses. Immunohistochemically, the tumor cells were positive to vimentin and weakly positive to desmin. Ultrastructurally, pinocytotic vesicles and cytoplasmic microfilaments with focal densities were found in the tumor cells. It is considered important to differentiate between the diagnosis of myxoid leiomyosarcoma and that of any other myxoid malignant tumor.

Desmin↗
PubMed1991

[Molecular diagnosis of gastric cancer].

Molecular mechanism of development and progression of gastric cancer which could be a base of molecular diagnosis was described. Amplification and point mutation of oncogenes are less common in gastric carcinomas, even though it is valuable for diagnosis. Amplification of ERBB2 seems to be an indicator for metastatic ability of gastric carcinoma. Overexpression of EGF/receptor system is a biologic marker for high malignancy. Diagnostic significance for scirrhous gastric carcinomas is found in over-expression of TGF beta, IGF and PDGF. Loss of heterozygosity on chromosomes 5q and 17p frequently occurs commonly in well differentiated type gastric cancer. More accumulation of molecular alterations in the development and progression of gastric cancer should make the molecular diagnosis more valuable in clinical field.

DNA, Neoplasm↗
PubMed1991

[Biological malignancy in human gastric carcinoma--molecular aspects].

Overexpression of many growth factors/receptors and decreased expression of TGF beta type I play an important role in progression of human gastric carcinomas. Abnormal regulation of transcription of these genes should be involved in cancer progression. Advanced gastric carcinomas showing metastasis sometimes reveal amplification of oncogenes. Development and progression of scirrhous gastric carcinoma are brought about by the accumulation of growth factors such as TGF beta, IGF, PDGF and FGF and by the amplification of SAM gene. Loss of heterozygosity (LOH) on chromosomes 1q, 5q and 17p frequently takes place in well differentiated type gastric carcinomas, while no LOH on chromosomes 1q and 5q occurs in poorly differentiated type. LOH on chromosomes 5q and 17p is detected even in early gastric carcinomas, although LOH on 1q and 7p is found only in advanced gastric carcinomas. Thus, the accumulation of multi-autocrine growth factors and multiple genetic alterations evidently participates in biological malignancy of gastric carcinomas.

Adenocarcinoma↗
PubMed1990

Expression of ERBB2 in human gastric carcinomas: relationship between p185ERBB2 expression and the gene amplification.

The expression of p185ERBB2 in a total of 34 human gastric carcinoma tissues as well as in corresponding normal mucosa was examined by Western blotting. More than 70% of both tumor tissues and normal mucosa showed p185ERBB2 expression at various levels. Eighteen (55%) cases revealed higher levels of p185ERBB2 in the tumor than in normal mucosa, while 13 (38%) cases showed lower levels in the tumor tissues. Higher expression of p185ERBB2 was frequently observed in well differentiated adenocarcinomas, with the incidence between well differentiated type and poorly differentiated type being significantly different (P less than 0.05). Comparative immunohistochemical analysis revealed the consistent results with p185ERBB2 expression obtained by Western blotting in well differentiated adenocarcinomas. Of the 34 cases, three well differentiated adenocarcinomas had extremely high levels of p185ERBB2. ERBB2 gene was amplified in two of the three tumors, but the amplification differed by the tumor site from where the sample was obtained. Another tumor which showed an extremely high level of p185ERBB2 but no gene amplification demonstrated a high level of binding protein to the TATA box that is located in the promoter of the ERBB2 gene. A high level of TATA-binding protein was also detected in gastric carcinoma cell lines which contain a single copy of ERBB2 gene and a high expression of p185ERBB2.

Blotting, Northern↗
PubMed1990

pp60c-src protein kinase activity in human gastric carcinomas.

We examined pp60c-src protein kinase activity in human gastric carcinoma cell lines and gastric carcinoma tissues as well as normal mucosa. pp60c-src kinase activity was detected in all 5 carcinoma cell lines at various levels. Of 16 gastric carcinoma tissues, 8 showed higher pp60c-src kinase activity in tumor tissues than in corresponding normal mucosa. However, the levels of expression of pp60c-src detected by Western blotting were not always consistent with the activities of pp60c-src protein kinase. These findings suggest that the increase in pp60c-src protein kinase activity might be brought about by post-translational changes.

Blotting, Northern↗
PubMed1990

DNA ploidy pattern and amplification of ERBB and ERBB2 genes in human gastric carcinomas.

The DNA ploidy pattern and amplification of ERBB and ERBB2 genes were examined in paraffin-embedded tissue from gastric carcinomas using flow cytometry and a slot-blot hybridization technique. The incidence of aneuploidy in well differentiated adenocarcinomas (56%) was significantly higher (p less than 0.05) than that in poorly differentiated adenocarcinomas (21%). The DNA ploidy pattern was not remarkably different between the primary tumors and metastatic deposits in lymph nodes. Of the nine specimens having an aneuploid stem cell line in the primary tumor and/or in metastases, three showed ERBB2 gene amplification and one showed ERBB gene amplification. The incidence of epidermal growth factor (EGF) immunoreactivity in tumor cells showed no difference between diploid and aneuploid tumors. These findings indicate that aneuploidy is frequently associated with amplification of ERBB and ERBB2 genes.

DNA, Neoplasm↗
PubMed1990

Expression of several growth factors and their receptor genes in human colon carcinomas.

We have examined the expression of mRNAs for epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha), EGF receptor (EGFR), PDGF-A chain (PDGFA), PDGF-B chain (PDGFB) and PDGF receptor (PDGFR) genes in seven human colorectal carcinoma cell lines and 18 human colorectal carcinomas. In surgically resected specimens of the 18 colorectal tumors, TGF-alpha, EGFR, PDGFA, PDGFB and PDGFR mRNAs were detected at various levels in 15 (83%), 9 (50%), 18 (100%), 8 (44%) and 12 (67%), respectively. They were also detected in normal tissues. Interestingly, EGF mRNA was detected in only five (28%) of the tumors, but not in normal mucosa. Expression of EGF was also confirmed immunohistochemically in tumor cells. Of the five tumors expressing EGF, four expressed EGFR mRNA and showed a tendency to invade veins and lymphatics. All the colorectal carcinoma cell lines expressed TGF-alpha mRNA, and five cell lines expressed EGFR mRNA simultaneously. Production of TGF-alpha protein by DLD-1 and CoLo320DM cells was confirmed by TGF-alpha specific monoclonal antibody binding assay. The spontaneous 3H-thymidine uptake by DLD-1 was suppressed by an anti-TGF-alpha monoclonal antibody. PDGFA and PDGFB mRNA were also expressed in four cell lines, but PDGFR and EGF mRNA was not detected. These results suggest that human colorectal carcinomas express multi-loops of growth factors and that TGF-alpha produced by tumor cells functions as an autocrine growth factor in human colonic carcinoma.

Antibodies, Monoclonal↗