Biomedical subjects

Koshi Mimori

Publications and source records attributed to Koshi Mimori.

46 records · Page 3Linked to original sources

PubMed2003

Microsatellite instability is often observed in esophageal carcinoma patients with allelic loss in the FHIT/FRA3B locus.

We have previously reported a significant correlation between the progression of colorectal carcinoma and the loss of Fhit and Msh2 expression. This observation led us to investigate the effect of an allelic loss of the FHIT gene on esophageal cancer when coupled with a deficient mismatch repair system. In this study, 8 of 42 patients with esophageal cancer had microsatellite instability (MSI), and 29 cases demonstrated allelic loss (loss of heterozygosity or homozygous deletion) at the FHIT/FRA3B locus. All 8 MSI-positive cases showed allelic loss, while 13 of 34 MSI-negative cases retained both alleles, and a significant correlation was found between the incidence of MSI and allelic loss (p < 0.05). On the other hand, only 1 of the 8 MSI-positive patients exhibited neither Msh2 nor Fhit protein expression in both normal and carcinoma epithelial tissues, but neither a relationship between Msh2 expression and Fhit expression nor with the incidence of MSI was noted. This result indicated that the disruption of the mismatch repair system of Msh2 does not mainly lead to allelic loss of the FHIT/FRA3B locus as well as MSI in esophageal cancer. We concluded that MSI is significantly related to the allelic loss in the FHIT/FRA3B region, but Msh2 might be unrelated to the progression or oncogenic process in esophageal cancer.

Acid Anhydride Hydrolases↗

PubMed2003

Platelet-derived endothelial cell growth factor mediates Rho-associated coiled-coil domain kinase messenger RNA expression and promotes cell motility.

BACKGROUND: Platelet-derived endothelial cell growth factor (PD-ECGF), whose expression is increased in several cancers, is an endothelial cell mitogen and has chemotactic activity in vitro and angiogenic activity in vivo. Tumors with high PD-ECGF expression tend to have frequent lymph node metastasis and are associated with poor outcome. METHODS: We screened genes transduced by PD-ECGF transfection to the colon cancer cell line DLD-1 by using a complementary DNA microarray. Cell motility was evaluated by in vitro migration assay. Actin fiber polymerization was visualized by immunofluorescent detection of phalloidin. RESULTS: Rho-associated coiled-coil domain kinase (ROCK1) was found to be significantly overexpressed in PD-ECGF transfectants compared with mock cells. PD-ECGF transfectants showed higher cell motility than mock cells. The parental cell, DLD-1, with recombinant PD-ECGF showed higher cell motility than that without recombinant PD-ECGF, in which motility was blocked by the neutralizing antibody of PD-ECGF or Y-27632, a specific inhibitor of ROCK1. Moreover, the actin fiber polymerization, which is a marker of activation of ROCK1, was higher in PD-ECGF transfectants than in mock cells. CONCLUSIONS: PD-ECGF expression may be associated with cancer cell migration via activation of ROCK1. This may explain one mechanism by which tumors with high expression of PD-ECGF show aggressive behavior.

Acute-Phase Proteins↗

PubMed2003

Clinical significance of the expression of activin A in esophageal carcinoma.

Activin A is a member of the transforming growth factor beta (TGF-beta) superfamily and is a strong differentiation factor of embryonic stem (ES) cells. It is unknown whether activin A has any correlation with carcinoma cell differentiation. We investigated the expression of activin-betaA (Act-betaA) which is a subunit of activin A, its receptor type I and IIb (ActRI, ActRIIb) and its inhibitor, inhibin-alpha (Inh-alpha), which is a subunit of inhibin A in esophageal carcinoma by reverse transcription polymerase chain reaction (RT-PCR) method. Act-betaA was overexpressed in carcinoma tissues significantly (p=0.030). On the other hand, Inh-alpha, ActRI and ActRIIb were neither overexpressed, nor suppressed. In immunohistochemistry and in situ hybridization analysis, Act-betaA expression was mainly derived from carcinoma cells. The mRNA expression of Act-betaA was not associated with carcinoma cell differentiation but lymph node metastasis (n0, 1, 2 vs. n3, 4; p=0.013) and clinical stage (I, II, III vs. IV; p=0.026). Moreover, patients with high mRNA expression of Act-betaA had a tendency to show poor prognosis compared to those with low mRNA expression (p=0.064). The finding indicated that activin A expression might not be associated with carcinoma cell differentiation but tumor aggressiveness such as lymph node metastasis in esophageal carcinoma.

Activin Receptors↗

PubMed2002

Genetic alterations of the tumor suppressor gene WWOX in esophageal squamous cell carcinoma.

The WWOX (WW domain containing oxidoreductase) gene was recently identified as a candidate tumor suppressor gene at 16q23.3-24.1, a chromosome region that spans the common fragile site FRA16D. To evaluate the potential role of the WWOX gene in esophageal squamous cell carcinomas, we examined 36 tumors for genetic alterations of the WWOX gene. Loss of heterozygosity (LOH) at the WWOX locus was observed in 14 (39%) tumors. A tumor-specific missense mutation was found in one tumor, and LOH analysis had shown that the other allele was missing. Furthermore, we detected aberrant WWOX gene transcripts with absence of exons 6-8 in two tumors, and complete absence of transcript in one tumor. These results indicate that alteration and inactivation of the WWOX gene may play a role in esophageal squamous cell carcinogenesis.

Aged↗

PubMed2002

A single-nucleotide polymorphism of SMARCB1 in human breast cancers.

The gene SMARCB1 has been considered a candidate for a tumor-suppressor gene. Nucleotide alterations in SMARCB1 have been reported, primarily in association with malignant rhabdoid tumor cases. We carried out a search for mutations in SMARCB1 in 60 human gastro-intestinal tract carcinoma cases, 122 breast cancer cases, and 36 human cancer cell lines. A single-nucleotide polymorphism (SNP) at codon 152 with an amino acid change (Asn to Asp) was found in 2 of 122 (1.6%) breast cancer cases, and another SNP at codon 299 without an amino acid change was found in tumor and normal tissues from 7 (5.7%) cases. Codons 152 and 299 of SMARCB1 are localized near or within the binding site for the cMYC protein. The amount of immunoprecipitated cMYC protein was reduced in two different cell lines expressing the codon 152 polymorphic SMARCB1 clone compared with those expressing wild-type SMARCB1, regardless of the identical expression of SMARCB1 protein in both cell lines. Therefore, the SNP at codon 152 is considered to be one of the coding SNPs that alters the SMARCB1-cMYC complex, which regulates various tumor-suppressor related genes against cancer. In addition, we identified three types of splicing isoforms, a 27-bp deleted gene, a 51-bp inserted gene, and a consensus gene, in both carcinoma tissues and in normal tissues; however, no clinical significance was observed for those isoforms. We found a nucleotide change at codon 152 of SMARCB1 that may alter the amount of immunoprecipitated cMYC protein, but we finally determined that SMARCB1 is highly conserved in human solid carcinomas.

Base Sequence↗

PubMed2002

Analysis of the gene-expression profile regarding the progression of human gastric carcinoma.

BACKGROUND: Tumor tissue consists of a variable mixture of tumor and host-cell populations. Recent developments in laser microdissection (LMD) and cDNA microarray analysis have encouraged us to study the differential gene expression profiles among normal cells, primary carcinoma cells, and metastatic carcinoma cells in cases of gastric carcinoma. METHODS: Total RNA was extracted from the cells obtained by means of LMD from the primary carcinoma, the corresponding gastric epithelium, and the lymph node metastasis in 5 cases of primary gastric carcinoma. RNA was amplified by the T7-based amplification system to be applied to a cDNA microarray. Thereafter, the differentially expressed genes among the 3 populations were evaluated. RESULTS: cDNA samples for microarray studies were successfully obtained from each cell population of 5 cases. The cDNA microarray demonstrated that several interesting genes, such as cell-cycle regulators and growth factors, were overexpressed in the metastatic cells compared with in the primary carcinoma cells. Oncogenes and cell-adhesion molecules were more overexpressed in the primary carcinoma cells than in the normal cells. On the other hand, caspase 8 and cadherin were more suppressed in the primary carcinoma cells than in the normal cells. Interestingly, among the matrix metalloproteinase family, only MMP7 was identified as a differentially overexpressed gene in both the primary carcinoma and the metastatic cells in comparison with the normal cells. CONCLUSIONS: This study demonstrated that the combined use of LMD, T7-based amplification, and a cDNA microarray enabled us to identify genes directly associated with each population of tumor tissue. The method will open up new possibilities for the precise gene analysis of tumor progression and metastasis.

Adenocarcinoma↗

PubMed2002

Localization of thymidine phosphorylase expression in colorectal carcinoma tissues by in situ RT-PCR assay.

Abundant expression of thymidine phosphorylase (TP) mRNA and protein was observed in human carcinoma tissues relative to the corresponding normal tissues. However, the distribution of cells that express TP has not yet been determined. In this study, we examined enzyme activity of TP in 24 primary colorectal carcinoma tissues and the corresponding normal tissue. Using in situ reverse-transcription polymerase chain reaction (RT-PCR), a new methodology to determine the localization of genes of interest objectively and clearly, cell distribution was compared. The expression of TP mRNA is observed in normal infiltrating cells adjacent to colon carcinoma cells by in situ RT-PCR. Similar to the protein activity, the average TP mRNA expression (amplified products/x400 field) in cases of Dukes C and D is 76.8, while that of Dukes A and B is 42.5, being significantly different (p = 0.001). Moreover, the number of amplified products in colon carcinoma tissues showed a significant correlation with the enzyme activity evaluated by high-performance liquid chromatography (p < 0.01, R = 0.76). In conclusion, the expression of TP mRNA is localized in stromal tissues as determined by in situ RT-PCR and can reflect the level of TP enzyme activity.

Adenocarcinoma↗

PubMed2002

[Recent advances in the diagnosis and treatment of colorectal cancers].

We review recent developments in the diagnosis and treatment of colorectal cancer. In diagnosis, the detection of the APC gene mutation in stool samples has had a strong impact because of its practical usage for mass screening. Several reports have indicated that the molecular detection of a very small number of cancer cells in the peripheral blood, bone marrow, or lymph nodes yields adequate information on recurrent disease. Several new markers were reported as a significant indicators of cancer development, invasion, or metastasis. In treatment, determination of microsatellite instability may be useful to select good candidates for 5-fluorouracil-based chemotherapy. New molecular targets have been reported, including epidermal growth factor receptor inhibitor, matrix metalloproteinase inhibitors, etc. Gene therapy with p53 or FHIT had undergone successful clinical trials. Tumor-specific immunotherapy with dendritic cell vaccination has also been achieved. In conclusion, many efforts to overcome colorectal cancer will soon open new therapeutic windows.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2002

Prognostic score of gastric cancer determined by cDNA microarray.

PURPOSE: To estimate gastric cancer patients' prognosis more comprehensively,we tried to develop a prognostic scoring system using a cDNA microarray. EXPERIMENTAL DESIGN: RNA was extracted from tumor/normal paired samples of 43 patients with gastric cancer, and cDNA microarray hybridization was performed. RESULTS: We selected 78 genes that were differentially expressed between aggressive and nonaggressive groups with respect to five conventional pathological factors. Next, we determined a coefficient for each gene. Thereafter a prognostic score was calculated by summing-up the value for each gene. It ranged from -47 to 201 with a median of 114. There were two peaks in its distribution. Ten of 11 patients who were alive with no evidence of recurrence >5 years after the operation showed a score of <100 points, whereas all 19 patients who died of disease showed >100 points. In 13 patients who were alive but the follow-up time was <5 years, 2 of the 3 patients with >100 points revealed recurrent disease during the follow-up. CONCLUSIONS: These findings demonstrate that such a system with cDNA microarray can contribute to the comprehensive analysis of malignant behavior of the tumor and may provide accurate information on prognosis.

Blotting, Northern↗

PubMedDate not supplied

INI-1, a partner gene of ALL-1, is highly conserved in human acute leukemia.

Recently, much interest have been focused on the role of INI-1, a partner gene of transfusion protein All-1 for leukemogenesis of acute leukemia cases. We found the presence of a mutation at codon 152 in INI-1 that resulted in a conservative amino acid change in cDNA and genomic DNA from an AML patient. We also found the known polymorphic nucleotide change at the third letter of codon 299 in exon 7 of INI-1 in 3 of 31 ALL cases and in 4 of 30 AML cases. In conclusion, INI-1, a partner gene for ALL-1, is considered to be highly conserved in acute leukemia cases.

Chromosomal Proteins, Non-Histone↗