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Sakae Itoga

Publications and source records attributed to Sakae Itoga.

8 recordsLinked to original sources
PubMed2005

Expression of the fetal-oncogenic fibroblast growth factor-8/17/18 subfamily in human hematopoietic tumors.

The fibroblast growth factors (FGFs) are involved in hematopoiesis and tumorigenesis. However, little is known about the contribution of the FGFs identified within the past 10 years to leukemogenesis. To elucidate whether these FGFs (FGF-8, -9, -10, -11, -12, -13, -14, -16, -17, -18, -19, -20, and -21) are expressed in leukemic cells, we performed RT-PCR analyses using 28 cell lines. The members of a fetal-oncogenic subfamily, FGF-8/-17/-18, were often expressed (53.5%, 25.0%, and 32.1%) with the co-expression of their receptors. Realtime quantitative-PCR analysis showed that FGF-8/-17 were aberrantly expressed in patients with acute leukemia. Moreover, cell proliferation assays revealed the proliferation activity of FGF-17 on leukemic cells expressing its receptors. These results demonstrated that certain recently identified FGFs play an important role in the growth of leukemic cells, possibly with an autocrine mode of action, and that these FGFs will become novel biomarkers for hematopoietic tumors.

Base Sequence↗
PubMed2005

A polymorphism in the 5'-flanking region of the CYP2E1 gene and elevated lung adenocarcinoma risk in a Japanese population.

Cytochrome P450 2E1 (CYP2E1) catalyzes the metabolic activation of the procarcinogen, N-nitrosodimethylamine, and cytotoxic carbon tetrachloride compounds. A tandem repeat polymorphism in the 5'-flanking region of the CYP2E1 gene was investigated in non-small cell lung carcinoma (NSCLC) patients to clarify the relationship between CYP2E1 gene polymorphism and lung cancer susceptibility. Blood samples were taken from 236 healthy control subjects (192 males and 44 females) and 111 patients (78 males and 33 females) who underwent surgery for NSCLC in Japan. DNA was isolated from these samples and the 5'-flanking region of the CYP2E1 gene was amplified by polymerase chain reaction and examined for tandem repeat polymorphisms using DNA fragment analysis. Sequence analysis confirmed the presence of three alleles, A2, A3, and A4 (361, 367, and 457 bp, respectively), with four genotypes observed in the lung cancer group and five genotypes in the control group. There was a statistically significant difference in genotype distribution between the lung adenocarcinoma and control group (P=0.0088, A4/A4 vs. non-A4/A4). In the lung adenocarcinoma group, the univariate risk estimates for the A4/A4 subgroup compared to the most common subgroup (A2/A2) was 4.300 (95% confidence interval = 1.358-13.618, P=0.0131). We conclude that the A4/A4 genotype of the 5'-flanking region of CYP2E1 was significantly more frequent in lung adenocarcinoma cases than in healthy controls and, therefore, may be involved in the development of lung adenocarcinoma.

Adenocarcinoma↗
PubMed2004

Comparative analyses of four different methods of genotyping ALDH2.

BACKGROUND: A number of methods of genotyping single nucleotide polymorphisms (SNPs) are currently available, ranging from the traditional restriction fragment length polymorphism (RFLP) and single-stranded conformational polymorphism (SSCP) to more sophisticated technologies. We determined the utility of three novel methods by genotyping aldehyde dehydrogenase-2 (ALDH2). METHODS: DNA was isolated from blood samples of 241 control subjects and 74 patients with esophageal cancer. The utility of three novel genotyping methods-melting curve analysis using a LightCycler, SNaPshot analysis using an ABI PRISM 310 genetic analyzer, and denaturing high-performance liquid chromatography using a WAVE DNA fragment analysis system-were compared with that of conventional fluorescent-based polymerase chain reaction (PCR)-SSCP using an ALF express DNA sequencer. RESULTS: The frequency of the mutant ALDH2*2 allele was significantly higher in patients with esophageal cancer (27.7%) than in control subjects (16.2%; p < 0.01; habitual alcohol drinkers). The melting curve analysis was accurate, more rapid, and easier to use than the SNaPshot analysis or denaturing high-performance liquid chromatography analysis. Fluorescent-based PCR-SSCP proved useful for analyzing a large number of samples. CONCLUSION: Melting curve analysis using the LightCycler is suitable for the genotyping of small numbers of samples in a routine clinical setting; fluorescent-based PCR-SSCP analysis using the ALF express DNA sequencer can be used for large-scale genotyping in epidemiologic studies.

Adult↗
PubMed2003

Transcriptional activity of the tandem repeat polymorphism in the 5'-flanking region of the human CYP2E1 gene.

BACKGROUND: There are remarkable interindividual differences in the expression of cytochrome P-4502E1(CYP2E1), which in turn may alter susceptibility to alcohol-related diseases and various cancers. We recently characterized the tandem repeat polymorphism in the 5'-flanking region of the human CYP2E1 gene and found that subjects with the homozygous mutant-type (A4/A4) may be at higher risk of developing esophageal cancer. In this study, we determined how this tandem repeat polymorphism alters transcriptional activities of the human CYP2E1 gene by transfection studies. METHODS: The 5'-flanking region (-2,562 base pair to +9 base pair) of the CYP2E1 gene from three individuals of different genotypes (A2/A2, A2/A4, A4/A4) was amplified by polymerase chain reaction. The polymerase chain reaction products placed in front of a luciferase reporter gene were transfected into human hepatoblastoma cells, human esophageal cancer cells, and human uterus cancer cells. Transcriptional activities were determined by the dual-luciferase assay. When indicated, ethanol (50 mM) was included in the culture medium. CYP2E1 messenger RNA levels in peripheral lymphocytes were measured by the real-time reverse transcription-polymerase chain reaction using the LightCycler system. RESULTS: The construct including the tandem repeat region exhibited luciferase activities in both A2 and A4 type. It was of note that the activity produced by the A4 allele was significantly greater than that by A2 allele in HeLa cells (p < 0.001). CYP2E1 messenger RNA levels in peripheral blood lymphocytes were comparable between the two genotypes. CONCLUSION: Transcriptional activity of the mutant allele of the tandem repeat polymorphism in the 5'-flanking region of the CYP2E1 gene is greater than that of the wild type.

5' Flanking Region↗
PubMed2002

Tandem repeat polymorphism of the CYP2E1 gene: an association study with esophageal cancer and lung cancer.

BACKGROUND: Cytochrome P-450 (CYP) enzymes have been shown to play important roles in chemical carcinogenesis. Reports have indicated that polymorphism in CYP1A1, CYP1A2, CYP2A6, CYP2E1, and CYP2D6 are associated with an altered risk of developing cancers of the lung, bladder, liver, and colon. CYP2E1 plays an important role in alcohol metabolism and participates in the metabolic activation of various carcinogens, such as N-nitrosodimethylamine. Recently, we found repeated sequences that consist of four alleles (A1, A2, A3, and A4) and six genotypes (A1/A2, A2/A2, A2/A3, A2/A4, A3/A4 and A4/A4) of the CYP2E1 gene. In the present study, we investigated whether these polymorphisms are associated with lung cancer and esophageal cancer. METHODS: DNA was isolated from blood samples of 192 healthy control subjects, 85 patients with lung cancer, and 82 patients with esophageal cancer in Japanese males. DNA samples were amplified by polymerase chain reaction in the 5'-flanking region of the CYP2E1 gene and in exon 12 in the ALDH2 gene. The tandem repeat polymorphisms were examined using DNA fragment analysis. Missense mutations in exon 12 of the ALDH2 gene were examined using fluorescence-based single strand conformational change polymorphism analysis. Written informed consent was obtained from all the subjects. RESULTS: In the CYP2E1 gene 5'-flanking region polymorphism, patients with esophageal cancer showed significantly higher frequency of the A4/A4 genotype compared with the control subjects (p = 0.02), but no difference was found in patients with lung cancer. The frequencies of the mutant ALDH2*2 allele were significantly higher in patients with esophageal cancer (27.7%) than in healthy control subjects (7.3%; p< 0.0001; habitual alcohol drinkers). CONCLUSIONS: The distribution of genotypes and allele frequencies of the tandem repeats of the 5'-flanking region of the CYP2E1 gene was significantly different in patients with esophageal cancer.

5' Flanking Region↗
PubMed2002

[Molecular diagnosis of hepatitis B virus and hepatitis C virus infection].

Detection of virus genomes and their mutants by molecular technology is essential in clinical practice for patients with hepatitis B virus(HBV) and hepatitis C virus(HCV) related liver diseases. We here briefly summarize genome structures of HBV-DNA and HCV-RNA. Also, we describe representative methods to detect and quantify HBV-DNA and HCV-RNA.

DNA, Viral↗