Biomedical subjects

E Tahara

Publications and source records attributed to E Tahara.

At least 145 records · Page 8Linked to original sources

PubMed1996

[Multistep stomach carcinogenesis].

Genetic instability, alterations of tumor suppressor genes as well as activation of oncogenes and aberrant expression of growth factor/receptor system found in human stomach carcinogenesis are overviewed. Aberrant expression and amplification of the c-met gene, inactivation of the p53 gene and amplification of the cyclin E gene are common events of both well differentiated and poorly differentiated gastric carcinomas. K-ras mutations, c-erbB2 gene amplification, loss of heterozygosity (LOH) and mutations of the APC, LOH of the bcl-2 gene and LOH at DCC locus are preferentially associated with well differentiated gastric cancer. On the other hand, microsatellite instability, reduction or loss of cadherin and catenins, K-sam and c-met gene amplification confer the development and progression of poorly differentiated or scirrhous gastric carcinomas. Interaction between cell-adhesion molecules in the c-met expressed cancer cells and hepatocyte growth factor from stromal cells is involved in morphogenesis of gastric cancer.

Adenocarcinoma↗

PubMed1996

Expression of cyclin D1, CDK4 and p27KIP1 is associated with the p16MTS1 gene status in human esophageal carcinoma cell lines.

p16MTS1/INK4A negatively regulates cell cycle progression by inhibiting the cyclin D/CDK4 complex that phosphorylates pRb. Frequent homozygous deletions of the p16 gene were recently found in various tumor cell lines. We examined the relationship between the genetic status of p16 and the expression of the cell cycle regulating molecules in human esophageal carcinoma cell lines. Out of eight human esophageal carcinoma cell lines, seven (67.5%) and six (75%) cell lines showed homozygous deletions of the p16 and p15 genes, respectively. All the p16-negative cell lines expressed high levels of cyclin D1, CDK4 and p27KIP1 proteins. Interestingly, the expression level of cyclin D1 was closely correlated to the levels of not only CDK4 but also p27KIP1 protein in p16-negative cell lines. Furthermore, all the p16-negative cell lines expressed Rb protein of approx 110 kDa which corresponds to the phosphorylated form, whereas the cell line with intact p15 and p16 genes did not express pRb. These results suggest that the expression of cyclin D1, CDK4, Rb and p27 is associated with the p16 gene status in esophageal carcinoma cell lines. Alternatively, loss of the p16 gene and subsequent over-expression of cyclin D1 and CDK4 might be involved in autonomous growth of esophageal carcinoma cells.

Adenocarcinoma↗

PubMed1996

Expression of cyclin E in human gastric adenomas and adenocarcinomas: correlation with proliferative activity and p53 status.

The expression of cyclin E in human gastric adenomas and adenocarcinomas was examined immunohistochemically to elucidate the role of cyclin E in stomach carcinogenesis. The expression of cyclin E was detected in 49% (90/182) of the adenomas and 59% (260/439) of the adenocarcinomas. The incidence of strongly positive cases (overexpression of cyclin E) was significantly higher in the adenocarcinomas (29%; 128/439) than in the adenomas (4%; 8/182) (p < 0.01). The incidence of the cyclin E expression showed a tendency to be higher in deeply invasive carcinomas and in the cases with lymph node metastasis, while the incidence did not differ among histological types. The expression of cyclin E was significantly correlated with the proliferative activity of the tumor cells measured by KI-67 antigen expression (p < 0.01). It was also correlated with the abnormal accumulation of p53 protein in the tumor cells (p < 0.01). These results suggest that overexpression of cyclin E and subsequent deregulation of the cell cycle may confer the development and progression of the gastric carcinomas.

Adenocarcinoma↗

PubMed1995

Abnormal retention of intron 9 in CD44 gene transcripts in human gastrointestinal tumors.

We have recently identified a new exon of the CD44 gene and demonstrated abnormal retention of a noncoding section, intron 9, in mRNA from bladder carcinomas. To analyze this further, the present study examined CD44 gene expression in cell lines from 14 esophageal, 3 colonic, and 4 breast carcinomas and in fresh samples from 20 colorectal carcinomas and corresponding normal colonic mucosa, using reverse transcriptase followed by the polymerase chain reaction (RT-PCR). This confirmed that there was abnormal assembly of several exons of the gene in cell lines and in tumor tissues from these organs. However, the most striking new finding was that intron 9 was present in RNA from 11 esophageal, 3 colon, and 1 breast carcinoma cell line, respectively. This was confirmed by RNase and DNase digestion analysis. Moreover, it was detected both in nuclear and cytoplasmic mRNA fractions, indicating that abnormal splicing of pre-mRNA occurs in cancer cells. The abnormal retention of intron 9 in CD44 gene transcripts was also demonstrated in tumor tissues from 16 (80%) of 20 patients with colon carcinoma, but there was no correlation with Dukes' stage. The biological significance of these observations is not yet understood. However, it is clear that, as with the abnormal expression pattern of CD44 variant exons, intron 9 retention is a good-candidate molecular diagnostic tool for colorectal carcinomas.

Base Sequence↗

PubMed1995

Concurrent amplification of cyclin E and CDK2 genes in colorectal carcinomas.

The genetic changes of cyclin A, DI, E and CDK2 were examined in human colorectal carcinomas by Southern-blot analysis. Gene amplification of cyclin E was detected in 5 of 53 (9.4%) primary colorectal carcinoma tissues. Interestingly, in 3 of 5 tumors showing cyclin E gene amplification, the CDK2 gene was amplified simultaneously with rearrangements. No obvious correlation was detected between gene amplification and clinicopathological features of colorectal carcinomas. Out of 7 colon carcinoma cell lines, 2 showed gene amplification of cyclin E without gene amplification of CDK2. No amplification of cyclin A or DI gene was found in any of the colorectal carcinoma tissues or colon carcinoma cell lines. Our results suggest that the concurrent amplification of cyclin E and CDK2 genes may play a role in colorectal carcinogenesis.

Aged↗

PubMed1995

Telomerase activity in human liver tissues: comparison between chronic liver disease and hepatocellular carcinomas.

Telomerase activity was examined in 105 frozen samples from human normal liver tissues, chronic liver disease, and hepatocellular carcinoma (HCC). Telomerase activity was positive in 28 of 33 HCC tissues regardless of tumor stage or size. Telomerase was expressed in 15 of 18 differentiated HCC nodules smaller than 3 cm. HCC tissues from all eight hepatitis B virus-positive patients were telomerase positive, while telomerase activity was not detected in normal liver tissues (0 of 4). Weak telomerase activity was only detected in 1 of 22 nontumor liver tissues from HCC patients. Interestingly, in 19 of 38 hepatitis tissues and 6 of 8 cirrhotic liver tissues from apparently cancer-free patients, very weak telomerase activity was detected. These results indicate that the expression of telomerase may play a crucial role in hepatocarcinogenesis.

Base Sequence↗

PubMed1995

Genetic alterations in human gastrointestinal cancers. The application to molecular diagnosis.

Gastrointestinal cancers involve genetic alterations in multiple oncogenes, multiple tumor suppressor genes, and multiple DNA repair genes. However, common and different genetic changes are observed in esophageal, gastric, and colorectal carcinomas, respectively. Inactivation of the p53 gene and expression of CD44 abnormal transcripts are common events that serve as a powerful tool for cancer diagnosis. Gene amplification of cyclin D is found preferentially in esophageal cancer, whereas gene amplification of cyclin E and c-met is frequently associated with gastric cancer. Mutations of the cyclin-dependent kinase inhibitor genes also occur in esophageal and gastric cancers. However, the scenario of multiple gene changes differs depending on the two histologic types of gastric cancer, because they may have different genetic pathways. Interestingly, the frequency of genetic instability is also quite different between the two types of gastric cancer. A new strategy of molecular diagnosis for gastrointestinal cancers, which started as routine work at Hiroshima City Medical Association Clinical Laboratory last August, may provide a new approach to cancer diagnosis for the next decade.

DNA Repair↗

PubMed1995

Retrovirally transmitted gene therapy for gastric carcinoma using herpes simplex virus thymidine kinase gene.

BACKGROUND: Herpes simplex thymidine kinase (HTK) is known to phosphorylate ganciclovir (GCV). Phosphorylated GCV is incorporated into genomic DNA, which leads to inhibition of cell growth and cell death in the replicating cells. Recently, much attention has been drawn to the use of retrovirally mediated gene therapy using HTK as a new therapeutic approach for brain tumors. However, little is known about this phenomenon in gastrointestinal carcinomas. METHODS: The authors transfected the HTK gene packaged in retroviral vector into TMK-1 gastric carcinoma cells (TMK-HTK cells). Sensitivity of TMK-HTK cells to GCV was examined in vitro. Moreover, TMK-HTK cells were transduced into nude mice subcutaneously, and the effects of GCV therapy was examined at the concentration of 20 mg/kg daily for 14 days. RESULTS: TMK-HTK cells were sensitive to GCV at the concentration of 0.1 to 100 micrograms/ml in a dose- and time-dependent manner in vitro. Moreover, 12 of 13 TMK-HTK tumors, which were transduced into nude mice subcutaneously, shrunk from the average diameter of 6.5 mm. CONCLUSION: The results indicate that retrovirally transmitted gene therapy with GCV may provide a new therapeutic approach for treatment of gastric carcinomas.

Animals↗

PubMed1995

Expression of amphiregulin in human gastric cancer cell lines.

BACKGROUND: Amphiregulin (AR) is a novel gene of the epidermal growth factor (EGF) family. The authors have already reported that AR mRNA was expressed by human gastric carcinoma cells at various degrees, and its expression was induced by the treatment with EGF or transforming growth factor-alpha (TGF-alpha). METHODS: To elucidate the biologic role of AR in the stomach carcinogenesis, the effect of AR on the cell growth and the expression of growth factor/receptor genes in TMK-1 and MKN-28 gastric carcinoma cell lines was examined. Furthermore, to determine whether AR acts as an autocrine growth factor for gastric carcinoma cells, the authors introduced an antisense phosphorothioate oligodeoxynucleotide (S-oligo) against AR mRNA to these two cell lines. RESULTS: AR stimulated the growth of TMK-1 and MKN-28 cells in a dose dependent manner. The growth-promoting effect of AR was as potent as that of EGF or TGF-alpha. AR antisense S-oligo induced significant growth inhibition of both TMK-1 and MKN-28 cells compared with the control random S-oligo. Moreover, AR induced mRNA expression for AR itself, TGF-alpha, and EGF receptor in both cell lines. CONCLUSIONS: These results overall suggest that AR acts as an autocrine growth factor for these two gastric carcinoma cell lines and evokes the cascade induction of EGF and the TGF-alpha/receptor system.

Adenocarcinoma↗

PubMed1995

Immunohistochemical analysis of nm23 gene product in human gallbladder carcinomas.

The expression of nm23, the product of a candidate suppressor gene for tumour metastasis, was examined immunohistochemically in human gallbladder carcinomas and compared with clinicopathological features. Seventy-eight (72%) of 107 carcinomas expressed nm23 protein regardless of histological type, while non-neoplastic mucosa occasionally showed very weak immunoreactivity to nm23. No obvious correlation was observed between nm23 protein expression and depth of tumour invasion or tumour stage. The expression of nm23 protein was detected in 60% and 74% of the cases with and without lymph node metastasis, respectively, indicating no relationship to metastatic ability. Fifty-eight percent of the cases showed reduction of nm23 immunoreactivity in tumour cells invading the stroma at the border of tumour cell nests compared with cells at the centre of the tumour. Only 7% of the cases showed increased nm23 expression in tumour cells at the border. These results suggest that in gallbladder carcinoma decreased expression of nm23 may not have implications for metastasis but may play a part in local invasion.

Carcinoma↗

PubMed1995

Are Japanese and European gastric cancer the same biological entity? An immunohistochemical study.

To examine the suggested biological difference between Japanese and British gastric cancers, immunohistochemistry was used to demonstrate eight markers of biological activity in a matched series of 40 Japanese and 33 British cases. There were no differences in the proportions of Japanese and British tumours positive to epidermal growth factor, epidermal growth factor receptor, transforming growth factor alpha, cripto or p53. A significantly greater proportion of British tumours were positive to c-erbB-2 whilst a significantly greater proportion of Japanese tumours were positive to nm23. British tumours had a significantly greater mean proliferating cell nuclear antigen proliferation index than Japanese tumours. These differences could be clinically significant.

Adult↗

PubMed1995

Frequent amplification of the cyclin E gene in human gastric carcinomas.

We searched for genetic alterations of the cyclin D1 and cyclin E genes in 45 human gastric carcinoma tissues. Expression of cyclin E mRNA and protein was also analyzed in eight of them by Northern and Western blots and immunohistochemical staining. The cyclin E gene was amplified 3-10 fold in seven gastric cancer tissues (15.6%), of which six were advanced gastric cancers. All of the cases with the cyclin E gene amplification displayed lymph node metastasis. Moreover, the case with the gene amplification overexpressed the cyclin E mRNA and protein. One of eight gastric cancer cell lines, MKN-7, shared the cyclin E gene amplification, and all of the gastric cancer cell lines expressed high levels of the cyclin E mRNA and protein even without gene amplification. Amplification of the cyclin D1 gene was not observed in any of the gastric carcinoma tissues or gastric carcinoma cell lines. These results suggest that the gene amplification and overexpression of cyclin E play an important role in the abnormal growth and progression of gastric carcinoma.

Aged↗

PubMed1995

Restoration of the cellular senescence program and repression of telomerase by human chromosome 3.

Telomeres, at the end of chromosomes, shorten with each cell division, resulting in cellular senescence. Tumor cells, unlike normal somatic cells, express a telomerase that maintains the telomere length. Deletion of a gene(s) on chromosome 3 is common in human renal cell carcinoma (RCC) and reintroduction of a normal chromosome 3 into an RCC immortal cell line restored the program of cellular senescence. The loss of indefinite growth potential was associated with the loss of telomerase activity and shortening of telomeres in the RCC cells with a normal chromosome 3. However, microcell hybrids that escaped from senescence and microcell hybrids with an introduced chromosome 7 or 11 maintained telomere lengths and telomerase activity similar to those of the parental RCC23. Thus, restoration of the cellular senescence program by chromosome 3 is associated with repression of telomerase function in RCC cells.

Base Sequence↗

PubMed1995

Carcinosarcomas of the esophagus.

Two cases of carcinosarcoma of the esophagus are reported. Both were polypoid tumors occurring in the middle of the intrathoracic esophagus. The tumors were predominantly composed of spindle-shaped sarcoma cells with some squamous cell carcinomas (SCC). One tumor showed many bizarre giant cells with filamentous materials in the cytoplasm. Microscopical examination of both tumors revealed transition from SCC to sarcoma cells. Immunohistochemically, the spindle-shaped sarcoma cells in both tumors displayed a strongly positive immunoreaction to alpha-smooth muscle actin, as did the bizarre giant cells of one tumor to sarcomeric actin. SCC and a few spindle-shaped sarcoma cells near the SCC showed a positive immunoreaction to cytokeratin. Electron microscopy revealed that the spindle-shaped cells had many myofilaments with dense bodies and that the bizarre giant cells had sarcomere structures with Z-bands in their cytoplasm. These findings indicate that both tumors were carcinosarcomas of SCC and myogenic sarcoma. We considered that sarcoma cells might originate in SCC, representing its metaplastic differentiation, or that both SCC and sarcoma might originate in a pluripotent stem cell.

Aged↗

PubMed1995

In situ mRNA hybridization technique for analysis of metastasis-related genes in human colon carcinoma cells.

The purpose of this study was to determine whether the expression level of several genes that regulate different steps of the metastatic process correlates with the metastatic potential of human colon carcinoma cells. The mRNA expression level for epidermal growth factor receptor (growth), basic fibroblast growth factor and interleukin-8 (angiogenesis), type IV collagenase (invasion), E-cadherin and carcinoembryonic antigen (adhesion), and the multidrug resistance gene mdr-1 (drug resistance) in the human KM12 colon carcinoma cell lines and clones with different metastatic potential was measured by Northern blot analysis and by in situ hybridization technique. Highly metastatic KM12SM and KM1214 cells growing in culture uniformly expressed high levels of epidermal growth factor receptor, basic fibroblast growth factor, and carcinoembryonic antigen mRNA, whereas cultures of low metastatic KM12C, clone 1, clone 3, and clone 6 cells displayed heterogeneous patterns of expression. KM12C (low metastatic) and KM12SM (highly metastatic) cells were implanted into the subcutis (ectopic) or the wall of the cecum (orthotopic) of nude mice. The mRNA expression level for epidermal growth factor receptor, basic fibroblast growth factor, interleukin-8, type IV collagenase, carcinoembryonic antigen, and mdr-1 was increased in the cecal wall tumors as compared with subcutaneous tumors or in vitro cultures. These data demonstrate a direct correlation between constitutive and inducible expression of several metastasis-related genes and the metastatic potential of human colon carcinoma cells.

Adenocarcinoma↗

PubMed1995

[Expression of sdi1, a potent inhibitor of cdk2 kinase, cdk2 and G1 cyclins and mutation of sdi1 in human gastric carcinomas].

Sdi1, also known as Cip1/Waf1, is a potent inhibitor of G1 cyclin-dependent kinases, which is induced by wild type p53 but not by mutant p53. Expression of mRNAs for sdil, cdk2 and G1 cyclins was examined in gastric carcinomas. All the cell lines expressing very low or undetectable level of sdil mRNA contains p53 gene abnormalities, while the cell lines expressing high level of sdil shares wild type p53 gene. An exception was a cell line MKN-28 with mutated p53 gene which expressed mRNAs for sdi1, cdk2 and G1 cyclins at high levels, p21 point mutation was detected in one (MKN-28) of the eight cell lines. These result suggest that low level of sdil and subsequent overexpression of cdk2 and G1 cyclins might be involved in deregulated growth of gastric carcinomas. It is likely that gene alteration of sdil and subsequent loss of function may have implication for cdk2 and G1 cyclins expression.

CDC2-CDC28 Kinases↗

PubMed1995

[Abnormal transcription of cell adhesion molecule CD44 in human gastric carcinomas].

CD44 abnormal transcription in gastric carcinomas is overviewed. The overexpression of aberrant CD44 transcripts detected by RT-PCR/Southern blot hybridization method is a common genetic event in gastric carcinomas regardless of the histological type or clinicopathological stage. In addition, 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 the well differentiated and the poorly differentiated type gastric carcinomas have different genetic pathways.

Adult↗

PubMed1995

Fibrolipomatous hamartoma of the lung: a case report and review of the literature.

A fibrolipomatous hamartoma of the lung in a 57-year-old Japanese man is reported. Computed tomography revealed an abnormal mass with fatty and soft tissue densities in the upper portion of the right lung, indicating a liposarcoma. Upon resection, the tumor was found to consist of a 7.5 x 4.0 cm soft, yellowish mass continuous with a 3.0 x 1.5 cm polyp. The tumor was composed primarily of mature fibro-adipose tissue with some glandular and cartilaginous components, which identified it as a fibrolipomatous hamartoma. Follow-up studies of the patient for two years after surgery found no sign of malignancy. Thus, lipomatous or fibrolipomatous hamartoma should be considered as a possible diagnosis whenever atypical lipomatous lung tumors are encountered.

Adipose Tissue↗