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H Kuniyasu

Publications and source records attributed to H Kuniyasu.

70 records · Page 4Linked to original sources
PubMed1994

Expression of CD44 abnormal transcripts in human gastric carcinomas.

Twenty gastric carcinoma cases were studied for the detection of CD44 aberrant transcripts using a cDNA/PCR/blot-hybridization technique which can detect splice variants containing an aberrant exon 11 of the CD44 gene. All the tumor tissues as well as their metastatic foci demonstrated overexpression of CD44 splice variants of more than 1.0 kbp than corresponding normal gastric mucosas. Six out of nine (66.7%) well-differentiated or intestinal type gastric cancers overexpressed more than three aberrant transcripts, whereas ten out of eleven (90.9%) poorly differentiated or diffuse type cancers overexpressed single or two lower molecular weight variants. These results indicate that the detection of CD44 transcription variants can serve as a powerful tool for the diagnosis of gastric cancer. It is also suggested from the difference in variant expression pattern that well-differentiated type and poorly differentiated type gastric carcinomas have different genetic pathways.

Adult↗
PubMed1994

Gene alterations in intestinal metaplasia and gastric cancer.

PURPOSE: To review genetic alterations in precancerous lesions and adenocarcinoma of the stomach. RESULTS: Telomere reduction, tpr-met oncogenic rearrangement, overexpression of cripto, p53 mutations, adenomatous polyposis coli gene mutations and K-ras mutations, which are frequently associated with the well differentiated or intestinal type of stomach cancer, were found in intestinal metaplasia and adenoma of the stomach. CONCLUSIONS: Among these genetic alterations, reduction of telomere repeat arrays might be the initial step in the genetic instability of stomach carcinogenesis. Some of the well differentiated type stomach cancers may develop by an accumulation of multiple gene changes similar to those of colorectal cancer.

Base Sequence↗
PubMed1994

[Genetic characteristics of scirrhous gastric carcinomas].

Genetic characteristics of scirrhous gastric carcinomas are overviewed. Scirrhous carcinomas of the stomach frequently show amplification of c-met and K-sam oncogenes as well as overexpression of 6.0 kb c-met abnormal transcript. For the formation of productive fibrosis and the diffuse infiltrative growth pattern of this malignancy, the essential factors would be not only the loss of cell adhesion molecule function through depressed expression or loss of cadherin or catenin, but also the synchronous overexpression of growth factors from the cancer cells including TGF-beta, PDGF, IGF-II and basic FGF with intimate cancer-stromal interaction through paracrine loop of IL-1 alpha/HGF system.

Adenocarcinoma↗
PubMed1993

Aberrant expression of c-met mRNA in human gastric carcinomas.

We examined mRNA expression for c-met encoding hepatocyte growth factor receptor in 8 gastric carcinoma cell lines and 31 surgically resected gastric carcinoma tissues by Northern-blot analysis. Two forms of the transcript, sized 7.0 kb and 6.0 kb, were found in gastric carcinomas. Transcripts of both sizes were detected at various levels in all the gastric carcinoma cell lines except the MKN-74 line, which expressed only the 7.0-kb form. Of the 31 gastric carcinomas, 15 (48%) over-expressed the 7.0-kb transcript when compared with non-neoplastic mucosa. The 6.0-kb transcript of the c-met gene was expressed at considerable levels in 52% of the gastric carcinoma tissues, whereas it was only slightly expressed in non-neoplastic mucosa of a small number of cases. An important finding was that expression of the 6.0-kb transcript was closely correlated with tumor staging, lymph-node metastasis and depth of tumor invasion. These results, overall, suggest that the 6.0-kb transcript of the c-met gene might participate in the development and progression of gastric carcinomas.

Blotting, Northern↗
PubMed1993

Expression of growth factors and their receptors in human esophageal carcinomas: regulation of expression by epidermal growth factor and transforming growth factor alpha.

The expression of mRNAs for epidermal growth factor (EGF), transforming growth factor alpha(TGF alpha), EGFR, platelet-derived growth factor (PDGF) A and B chain, PDGF receptor (PDGFR), transforming growth factor beta (TGF beta), erbB-2 and estrogen receptor (ER) genes was first examined in 6 human esophageal carcinoma cell lines, 6 xenoplanted and 15 surgically resected esophageal carcinomas. Secondly, the effect of EGF and TGF alpha on the expression of these genes by the TE-1 esophageal carcinoma cell line was investigated. The expression of EGF mRNA was detected in 8 (29.6%) of 27 tumors including the cell lines, whereas the TGF alpha and EGFR genes were expressed in 21 (77.8%) and 24 (88.9%) tumors respectively. PDGF B chain and PDGFR were detected in 18 (66.7%) and 20 (74.1%), respectively, and ER mRNA was observed in 16 (59.3%) tumors. Genes for PDGF A chain and TGF beta and the erbB-2 gene were commonly expressed. On the other hand, exogenous EGF and TGF alpha stimulated the expressions of fos and myc genes by TE-1 cells. The expression of mRNAs for TGF alpha, PDGF A and B chain and the erbB-2 genes was also increased after treatment with EGF. TGF alpha increased the accumulation of mRNAs for EGF, TGF alpha, EGFR, PDGF A and B chain and the erbB-2 gene. Moreover, the expression of mRNAs for interstitial collagenase, stromelysin and type IV collagenase was increased after EGF or TGF alpha treatment. These results indicate that EGF and TGF alpha may regulate the multi-growth-factor receptor expression and may play a central role for tumor invasion and metastasis as autocrine modulators for human esophageal carcinoma.

Adenocarcinoma↗
PubMed1993

Expression of amphiregulin, a novel gene of the epidermal growth factor family, in human gastric carcinomas.

The expression of mRNA for amphiregulin (AR), a novel gene of the epidermal growth factor family, was examined in 8 human gastric carcinoma cell lines and 32 gastric carcinoma tissues as well as corresponding normal mucosa. Of the 8 gastric carcinoma cell lines, 7 expressed 1.4 kb AR mRNA at various levels. The expression of AR mRNA by TMK-1 and MKN-28 cells was increased by treatment with epidermal growth factor or transforming growth factor a. In surgical cases, all the gastric carcinoma tissues and their adjacent normal mucosa expressed AR mRNA. Interestingly, 20 (62.5%) out of 32 tumors expressed AR mRNA at higher levels than their corresponding normal mucosas (tumor/normal > or = 1.2). No obvious correlation was observed between the AR mRNA levels and the histological types or tumor staging of gastric carcinoma. Immunohistochemically, AR protein was localized to the cytoplasm and/or nucleus in tumor cells. These results suggest that AR produced by tumor cells may be involved in the pathogenesis and/or progression of human gastric carcinoma.

Adult↗
PubMed1993

[Metastasis related genes and malignancy in human esophageal, gastric and colorectal cancers].

Alterations in multiple oncogenes and multiple tumor suppressor genes are observed in human gastro-intestinal cancer. Among them, the most frequently implicated in malignancy and metastasis of esophageal carcinoma may be amplification and overexpression of the human cyclin D gene. In gastric carcinoma, amplification and abnormal expression of the c-met gene encoding receptor for hepatocyte growth factor (HGF) may contribute to the tumor progression and metastasis. Interaction between cadherin in c-met overexpressed tumor cells and HGF from fibroblast may play an important role in morphogenesis of two histological types of stomach cancer. During stomach carcinogenesis the clone having critical p53 mutations may expand selectively to make up a finally advanced stage of malignancy and show metastasis. In colorectal cancer, loss of heterozygosity of the RB, p53 and DCC genes is frequently associated with liver metastasis. Overexpression of nm23 may participate in carcinogenesis and the reduction in nm23 expression is involved in metastasis in gastric and colorectal cancers.

Colorectal Neoplasms↗
PubMed1992

The level of a transcription factor Sp1 is correlated with the expression of EGF receptor in human gastric carcinomas.

The expression of the transcription factor Sp1 and EGF receptor (EGFR) was examined on human gastric carcinoma cell lines and gastric carcinoma tissues as well as corresponding normal mucosa in order to clarify the mechanism of overexpression of EGFR gene without gene amplification. All 7 carcinoma cell lines expressed Sp1 mRNA, the levels of which were closely correlated with the expression of EGFR mRNA except for one cell line. The gel retardation analysis revealed that the levels of Sp1 mRNA were parallel to its DNA binding activities. In 18 surgical cases, 12 tumors expressed Sp1 mRNA at higher levels than normal mucosa. The cases with overexpression of Sp1 showed the high level of EGFR mRNA. These results suggest that overexpression of Sp1 in tumor cells may induce overexpression of EGFR without gene amplification in human gastric carcinomas.

Adult↗
PubMed1992

Frequent amplification of the c-met gene in scirrhous type stomach cancer.

Amplification of the c-met gene, that encodes hepatocyte growth factor receptor, was examined on human esophageal, gastric and colorectal carcinomas. Six (55%) of the 11 gastric carcinoma cell lines and 15 (23%) of the 64 advanced gastric carcinomas showed the c-met gene amplification. Among them, c-met amplification was detected in 5 gastric cancer cell lines, derived from scirrhous gastric carcinoma and in 5 (38%) of 13 scirrhous gastric carcinoma tissues. Furthermore, patients of gastric carcinoma with c-met amplification showed significantly advanced tumor stage and poorer prognosis than those without the amplification. Conversely, no amplification was detected in any of the esophageal and colorectal carcinoma cell lines as well as carcinoma tissues except one colonic carcinoma. These results overall suggest that amplification of the c-met gene might participate in carcinogenesis and progression of stomach cancer, especially scirrhous type stomach carcinoma.

Adenocarcinoma, Scirrhous↗
PubMed1992

p53 point mutations in primary human gastric carcinomas.

p53 point mutations in primary gastric carcinomas were analyzed by performing cDNA deoxynucleotide sequencing of the gene. Out of 16, 9 (56.3%) primary gastric carcinoma cases, including early cancer, showed one or more p53 point mutations in their open-reading frame, and 4 out of 9 cases had a p53 point mutation within highly conserved domains. The characteristics of the p53 mutation spectrum observed in primary tumors were (a) frequent mutation at an A:T pair (50%, 7 out of 14 mutations), (b) high transversion incidence (29%, 4 out of 14 mutations), (c) no transition at CpG, and (d) no G:C to T:A transversion. Our results suggest that p53 mutation is a common event in gastric carcinoma occurring from the early stage of progression with its specific mutation spectrum.

Adult↗
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

[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

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↗
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↗