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Biomedical subjects

E Tahara

Publications and source records attributed to E Tahara.

At least 163 records · Page 9Linked to original sources
PubMed1995

Association of epidermal growth factor-related peptides and type I receptor tyrosine kinase receptors with prognosis of human colorectal carcinomas.

The frequency of expression and localization of cripto-1 (CR-1), amphiregulin (AR), transforming growth factor alpha (TGF alpha), epidermal growth factor receptor (EGFR) and erbB-2 were examined by immunohistochemistry in 45 carcinomas and adjacent non-involved normal colon mucosa. Thirty (66.7%), 24 (53.3%), 23 (51.1%), 23 (51.1%) and 13 (28.9%) of the 45 carcinomas showed positive staining for CR-1, AR, TGF alpha, EGFR and erbB-2, respectively, whereas 7 (15.5%), 17 (37.7%), 15 (33.3%), 20 (44.4%) and 0 (0%) of the corresponding non-involved normal mucosa specimens were reactive. Among 13 carcinomas with lymph node involvement, 10 (76.9%), 8 (61.5%), 10 (76.9%), 8 (61.5%) and 7 (53.8%) exhibited positive staining for CR-1, AR, TGF-alpha, EGFR and erbB-2, respectively. There was a statistically significant association between the frequency of either TGF alpha (P < 0.05) or erbB-2 (P < 0.05) expression and lymph node metastasis. In addition, a significantly higher frequency of positive staining for TGF alpha was observed in Dukes' grade C carcinomas (P < 0.05). Finally, significant trends for coexpression of EGFR and either TGF alpha (P < 0.01) or AR (P < 0.05) were detected in carcinomas. These data suggest that AR and TGF alpha may play an important role in the development of colorectal carcinomas through an autocrine mechanism involving EGFR, and demonstrate that TGF alpha and erbB-2 may be more reliable indicators of metastasis or prognosis than CR-1, AR or EGFR in human colon cancers.

Adenocarcinoma↗
PubMed1995

Multiparametric in situ messenger RNA hybridization analysis to detect metastasis-related genes in surgical specimens of human colon carcinomas.

We examined the expression of several genes that regulate different steps of metastasis in surgical specimens of human colon carcinomas. The expression of epidermal growth factor receptor (growth), basic fibroblast growth factor [(bFGF), angiogenesis], type IV collagenase (invasion), E-cadherin (adhesion), and multidrug-resistant (mdr)-1 (drug resistance) mRNA was examined using an in situ mRNA hybridization (ISH) technique and Northern blot analysis. Dukes' stage C and D tumors exhibited a higher level of expression (P <0.05) for bFGF, type IV collagenase, and mdr-1 mRNA than Dukes' stage B tumors. The expression level of epidermal growth factor receptor and E-cadherin did not correlate with the stage of the disease. The ISH technique revealed intertumoral heterogeneity for expression of several genes among Dukes' stage B neoplasms. In some Dukes' stage B tumors, we also found intratumoral heterogeneous staining for bFGF and type IV collagenase, with the highest expression level at their invasive edge. In Dukes' stage C and D tumors, the expression of these genes was more uniform. These results recommend the suitability of the multiparametric ISH analysis for metastasis-related genes to identify individual colon cancers with metastatic potential.

Blotting, Northern↗
PubMed1995

Telomerase activity in preneoplastic and neoplastic gastric and colorectal lesions.

Recent evidence indicates that telomerase activity may be necessary for cell immortality, which is required for the sustained and indefinite growth of most malignant cells. We analyzed telomerase activity in gastric and colorectal cancers and in gastric and colorectal precancerous lesions to determine whether malignant progression depends on the activation of telomerase and at what stage of carcinogenesis cells have detectable telomerase activity. Telomerase activity was measured by the telomeric repeat amplification protocol assay and was detected in 17 (85%) of 20 primary gastric carcinoma tissues and in 19 (95%) of 20 primary colorectal carcinomas, regardless of tumor staging and histological types. All nodal metastases, peritoneal metastases, and a recurrent gastric cancer tumor were positive. All cell lines established from gastric and colorectal cancers contained telomerase activity. In precancerous lesions, 10 (100%) of 10 colorectal tubular adenomas were telomerase positive, in addition to 3 (23%) of 13 gastric intestinal metaplasias and 1 (50%) of 2 gastric adenomas, whereas the corresponding gastric normal mucosas as well as colorectal mucosas were negative. These results indicate overall that reactivation of telomerase may occur at an early stage of carcinogenesis and may correlate well with malignant progression of gastric cancer. Telomerase activity thus may serve as a powerful additional tool for cancer diagnosis.

Adenocarcinoma↗
PubMed1994

Frequent loss of heterozygosity of the long arm of chromosome 7 is closely associated with progression of human gastric carcinomas.

Loss of heterozygosity (LOH) on the long arm of chromosome 7 was examined using 5 polymorphic marker probes on 98 gastric carcinomas to elucidate a novel locus for development and progression of the tumors. Twenty-six (32%) of 82 informative cases showed LOH on 7q on at least one locus of 5 loci. Among 5 loci, LOH at D7S95 locus was most frequent, the incidence being 53% in well-differentiated gastric carcinomas and 33% in poorly differentiated and scirrhous gastric carcinomas respectively. At 3 loci, c-met, D7S63 and D7S22, the incidence of LOH was about 30% and 10% in well-differentiated and poorly differentiated gastric carcinoma cases respectively. In contrast, LOH at D7S64 was not detected in any gastric-carcinoma cases. Deletion mapping of 7q revealed that D7S95 locus was the essential region of LOH. Eight (62%) of 13 cases with LOH at D7S95 locus belonged to the most advanced stage grouping. Furthermore, 6 (75%) of 8 cases with abdominal dissemination showed LOH at D7S95. Therefore, cases with LOH at D7S95 showed significantly worse prognosis than the cases without the LOH in the stage-III and stage-IV groups. These findings overall suggest that D7S95 locus on 7q may contain a candidate suppressor gene for the progression of gastric carcinoma.

Adenocarcinoma↗
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

Frequent replication errors at microsatellite loci in tumors of patients with multiple primary cancers.

Nearly 10% of cancer patients develop a second primary cancer within 10 years after surgical removal of the first tumor. Hence, detection of a genetic risk for developing multiple primary tumors would be of clinical importance. To investigate whether a genetic defect(s) involving the mismatch repair system constitutes an important risk factor in patients with multiple primary cancers, we examined replication errors (RER) at microsatellite loci in 79 primary cancers which had developed among 38 patients with multiple primary cancers. The RER(+) phenotype was observed at five microsatellite loci on chromosomes 2, 3, 11, or 17 in tumors from 34 (89%) of 38 patients with multiple primary cancers but only in 19 tumors from 174 patients (11%) with a single primary cancer. Our results suggested that: (a) genetic instability may play an important role in development of multiple primary cancers, and (b) testing for RER in a primary cancer may be an appropriate approach to detection of patients at high risk for developing multiple primary cancers.

DNA Repair↗
PubMed1994

Cripto, a member of the epidermal growth factor family, is over-expressed in human pancreatic cancer and chronic pancreatitis.

Cripto is a 188 amino-acid protein containing a central segment that shares amino-acid sequence homology with epidermal growth factor (EGF) and transforming growth factor alpha (TGF-alpha). The EGF receptor, EGF and TGF-alpha are expressed in the normal human pancreas, and are over-expressed in human pancreatic cancer. Therefore, in the present study we sought to determine whether cripto is found in the normal human pancreas and whether its expression is altered in pancreatic cancer. Because chronic pancreatitis (CP) is associated with interstitial fibrosis similar to that observed in pancreatic cancer, we also examined cripto expression in pancreatic tissues from patients with CP. In the normal pancreas, cripto immunoreactivity was found at moderate levels in most ductal cells and was present very faintly in a rare acinar cell. In 26 of 58 pancreatic cancers, cripto immunoreactivity was present in many cancer cells. Its presence was associated with advanced tumor stage, but not with shorter post-operative survival. Cripto was also present in acinar and ductal cells adjacent to the cancer cells, and in many ductal atrophic acinar cells in the CP samples. Northern blot analysis revealed a marked increase in cripto mRNA levels in the cancer and CP samples. By densitometry, there was a 11- and 4-fold increase in cripto mRNA levels in pancreatic cancer and CP respectively. Southern blot analysis did not reveal an increase in gene copies encoding cripto either in cancer or in CP. These findings indicate that cripto expression may contribute to disease progression in pancreatic cancer, and implicate cripto in the histopathological alterations that occur in the pancreas both in cancer and in CP.

Adolescent↗
PubMed1994

Expression of a 31-kDa lactoside-binding lectin in normal human gastric mucosa and in primary and metastatic gastric carcinomas.

The expression of lactoside-binding lectin L-31 was analyzed in normal mucosa and in primary and metastatic gastric carcinomas. Immunoblotting revealed L-31 lectin in extracts of normal and malignant gastric tissues from 26 patients. The L-31 level was higher in tumor than in normal tissue in 9/26 cases, similar in 14/26 cases, and lower in 3/26 cases. Anti-L-31 monoclonal antibodies (MAbs) were used in immunohistochemical analyses to compare lectin expression in specimens of primary gastric carcinomas and adjacent normal mucosa from 39 patients and in specimens of metastases and the corresponding primary gastric carcinomas from 74 patients. The lectin was detected in normal gastric epithelial cells and in all gastric carcinoma specimens, albeit in varying amounts. The L-31 level was significantly higher in the primary tumor than in adjacent normal tissue in 55% of the well-differentiated tubular carcinoma cases and in 50% of stage-III and -IV tumors. L-31 expression in liver metastases from well-differentiated tubular primary gastric carcinomas was higher in 31% of the cases relative to the corresponding primary cancers. Likewise, L-31 expression in metastases from poorly differentiated gastric carcinomas in lymph nodes was higher in 38% of the cases compared to the primary cancers. The higher expression of L-31 in primary cancers and metastases of certain types implicates this lectin in the metastatic phenotype, but the presence of L-31 in a primary cancer is not sufficient to allow the metastatic propensity of the tumor to be predicted.

Antibodies, Monoclonal↗
PubMed1994

Effect of hepatocyte growth factor on the expression of E- and P-cadherin in gastric carcinoma cell lines.

Hepatocyte growth factor (HGF), identical to scatter factor, (SF) is a secretory glycoprotein from fibroblasts which dissociates and increases the motility of various types of epithelial cells. After treatment of three gastric carcinoma cell lines (MKN-28, MKN-45 and TMK-1) with HGF (10 ng/ml), TMK-1 cells lost their tight cell to cell contact and showed marked scattering, while the two other cell lines remained unaffected. To learn about the underlying mechanism of the HGF induced scattering, we examined the expression of adhesion molecules and growth factor/receptor systems at the mRNA and protein level. The observed scattering of treated TMK-1 cells was associated with a reduction in the expression of E- and P-cadherin protein. The respective mRNA levels remained unchanged after HGF/SF treatment. In the two other cell lines, which showed no scattering, there were no changes in the expression of E- and P-cadherin. All other growth factors and their receptors examined (TGF-alpha, EGFR, c-met and c-erbB2) remained constant and were not affected by HGF treatment. The results suggest that HGF/SF may regulate cell adhesion in gastric carcinomas via E- and P-cadherin expression at the protein level.

Adenocarcinoma↗
PubMed1994

Loss of heterozygosity at the bcl-2 gene locus and expression of bcl-2 in human gastric and colorectal carcinomas.

The loss of heterozygosity (LOH) at the bcl-2 gene locus and the expression of the bcl-2 gene were examined in gastric and colorectal carcinoma cell lines and carcinoma tissues. LOH at the bcl-2 locus was detected in 24% (4/17) of gastric and 60% (6/10) of colonic carcinomas, all of which were well differentiated adenocarcinomas, whereas LOH was not seen in poorly differentiated ones. On the other hand, 24% (5/21) of poorly differentiated stomach cancers overexpressed bcl-2 gene, whereas no overexpression was detected in well differentiated stomach cancer. Three gastric and three colorectal carcinoma cell lines, all of which were derived from poorly differentiated adenocarcinomas, expressed considerable levels of bcl-2 mRNA and protein. These results suggest that LOH at the bcl-2 locus is frequently associated with well differentiated adenocarcinomas of the stomach and colon, and bcl-2 overexpression has implications for the development of poorly differentiated adenocarcinomas of the gastrointestinal tract.

Adenocarcinoma↗
PubMed1994

[Metastasis-related genes].

Genetic changes related to cancer metastasis are overviewed. hst-1/int-2 co-amplification is closely related to the metastatic potential of esophageal carcinomas. Multiple autocrine and paracrine loops including EGF, TGF-alpha/EGF receptor system and HGF/c-met system are related to the biological malignancy of gastric carcinoma in general. On the other hand, K-sam and c-erbB2 amplification are frequently found in the metastatic foci of poorly and well-differentiated type gastric carcinoma. Various splice variants of cell adhesion molecule CD44 are the potent marker of human carcinomas themselves as well as metastases. Reduction in the expression of nm23 is a relatively common event in the metastasis of various human cancers, including stomach and colorectal carcinomas.

Animals↗
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↗
PubMed1994

Effect of hepatocyte growth factor (HGF)/scatter factor (SF) on cell adhesion in gastric cancer.

Hepatocyte Growth Factor (HGF)/Scatter Factor (SF) is a secretory glycoprotein from stromal fibroblasts which binds to the transmembrane c-met receptor. This receptor is expressed from a variety of tumors, including gastric carcinomas. To look for a possible paracrine loop between gastric cancer cells and their surrounding fibroblasts in gastric carcinoma, the effect of HGF/SF treatment on the morphology and the expression of cell adhesion molecules was examined. The cell line TMK-1, established from poorly differentiated gastric carcinoma, responded with scattering after HGF/SF treatment. We found that the observed morphological changes were accompanied with a reduced expression of E- and P-cadherin protein in these cells. In a cell line established from well differentiated gastric carcinoma, named MKN-28, neither scattering nor changes in cadherin expression could be detected. This results suggested, that HGF/SF is a regulator of cell adhesion via affecting E- and P-cadherin. Taking into account, that only cells from poorly differentiated gastric carcinoma cell lines responded in scattering after HGF/SF treatment, paracrine secreted HGF/SF may play an important role in the pathogenesis of these type of gastric carcinoma in vivo.

Adenocarcinoma↗
PubMed1994

[Molecular diagnosis on gastrointestinal cancers].

Many of the genetic alterations related to carcinogenesis and progression such as gene amplification, deletion, mutation and overexpression can be analyzed on paraffin-embedded clinical materials. Genetic abnormalities of tumor suppressor gene such as p53 and APC (adenomatous polyposis coli) are good markers for differential diagnosis of gastrointestinal cancers. Gene amplification and overexpression of oncogenes and growth factors/receptors such as c-met, K-sam, c-erbB2, EGF and EGF receptor are biological marker of biological malignancy. Molecular diagnosis has been done in Hiroshima Medical Association Laboratory to make an objective diagnosis for border line lesions and to obtain information on the biological behavior of gastrointestinal cancers based on genetic alterations. Molecular analysis is a powerful tool to complement histological diagnosis of gastrointestinal lesions.

Gastrointestinal Neoplasms↗
PubMed1994

Cancer-stromal interaction through growth factor/cytokine networks implicated in growth of stomach cancer.

Stomach cancer shows multiple gene changes, including both oncogenes and tumor suppressor genes. Among them, the one most frequently implicated in stomach cancer is the abnormal expression and amplification of the c-met gene. Moreover, stomach cancer cells express a broad spectrum of growth factors and cytokines that not only serve autocrine or paracrine growth of tumor cells, but also organize the complex networks between tumor cells and stromal cells. However, the scenario of cancer-stromal interaction differs depending on the two histological types-the well-differentiated or intestinal type and the poorly-differentiated or diffuse type-as the two types of stomach cancer may have different genetic pathways. The interaction between cell-adhesion molecules in the c-met overexpressed tumor cells and HGF from activated fibroblast may be involved in the progression and the morphogenesis of stomach cancer.

Adenocarcinoma↗