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Yukimoto Ishii

Publications and source records attributed to Yukimoto Ishii.

At least 19 recordsLinked to original sources
PubMed2006

Detection of aberrations of ubiquitin-conjugating enzyme E2C gene (UBE2C) in advanced colon cancer with liver metastases by DNA microarray and two-color FISH.

Using DNA microarrays, the expression profiles of 1,700 genes in the primary tumor, liver metastases and paired normal tissue obtained from nine patients with advanced colorectal cancer was studied. Twenty genes were upregulated and only one gene was downregulated in the primary tumors. In the liver metastases, 39 genes were upregulated and only three genes were downregulated. There was no significant difference in gene expression between the primary tumors and the liver metastases. The most highly overexpressed gene in both the primary tumors and the liver metastases was the ubiquitin-conjugating enzyme E2C gene (UBE2C), located at 20q13.1. Additionally, two-color FISH analysis using probes for the region 20q13.1 and the chromosome 20 centromere revealed that amplification at 20q13.1 had occurred in 5 of 10 (50%) colon cancers. Comparison between the levels of gene expression and FISH results revealed that UBE2C expression is significantly changed by amplification at 20q13.1, suggesting genomic amplification as one mechanism of increased UBE2C expression. Our results showing aberrations in levels of gene expression and locus copy number of UBE2C suggest that this gene may play an important role in tumor progression leading to advanced colon cancer with liver metastasis.

Centromere↗
PubMed2006

A case of bone metastasis of colon cancer that markedly responded to S-1/CPT-11 combination chemotherapy and became curable by resection.

BACKGROUND: An oral combined fluoropyrimidine anticancer drug, tegafur/gimeracil/oteracil potassium (S-1), has recently been used alone or in combination for colon cancer. CASE PRESENTATION: The patient was a 42-year-old man with sigmoid colon cancer with direct invasion of the urinary bladder and multiple costal metastases. A diagnosis of T4, M1, stage IV sigmoid colon cancer was made, and curative resection was considered impossible. S-1 at 50 mg/m2 was administered by oral route from day 1 to day 14. Irinotecan (CPT-11) at 40 mg/m2 was administered by intravenous day 1 and 15. This treatment was followed by 2 weeks absent period, and repeated every 4 weeks. Six cycles of administration were performed in total. Following this treatment, the multiple costal metastases resolved. Down-staging to T3, M0, stage IIA was achieved, and curative resection was judged to be possible. CONCLUSION: Occasional cases in which S-1/CPT-11 therapy was effective have been recently reported. The patient's tumor became resectable despite the discovery of colon cancer associated with bone metastasis at the initial examination, offering hope for cancer patients.

Journal Article↗
PubMed2005

Phenylalanine breath test as a method to evaluate hepatic dysfunction in obstructive jaundice.

BACKGROUND: The purpose of this study was to investigate whether the hepatic dysfunction associated with obstructive jaundice can be measured from changes in expiratory 13CO2 levels after intravenous administration of l-[1-(13)C]phenylalanine, using a rat model of obstructive jaundice. MATERIALS AND METHODS: Under pentobarbital anesthesia, bile duct ligation (BDL) was performed (n=12). In the control group, simple laparotomy was performed (n=12). On postoperative day 7, 20 mg/kg l-[1-(13)C]phenylalanine was administered via the femoral vein. Phenylalanine breath test (PBT) was performed for 30 min. We compared single point of 13CO2 level (SPT: T: min) and sum of 13CO2 output (ST) values between BDL and control rats. We examined the correlation of SPT or ST with phenylalanine hydroxylase activity (PHA) and blood chemical parameters. RESULTS: Both SPT and ST values decreased in BDL compared to control 3 min after the start of PBT (SP10; 103+/-12 (per thousand) versus 84+/-16 (per thousand) P=0.025). PHA/g liver in BDL was significantly decreased compared to control (40.81+/-4.80 (U) versus 28.93+/-9.60 (U) P=0.008). PHA/g liver was correlated with SPT with correlation coefficient of more than 0.715, 10 min after the start of PBT, and the maximum correlation was at SP20 (r=0.801). Blood chemical parameters were correlated with S15 (total bilirubin, r=-0.717; alkaline phosphatase, r=-0.841; gamma-glutamyl transpeptidase, r=-0.759; alanine aminotransferase, r=-0.776; albumin, r=0.819). CONCLUSIONS: In the breath test with intravenously l-[1-(13)C]phenylalanine, hepatic dysfunction associated with obstructive jaundice could be measured in a short period.

Animals↗
PubMed2005

Expression of L-type amino acid transporter 1 (LAT1) in esophageal carcinoma.

BACKGROUND AND OBJECTIVES: It has been reported that amino acid transport systems play an important role in cell proliferation. Their activity is increased in malignant cells compared to benign cells. In this study, we investigated whether L-type amino acid transporter 1 (LAT1) is expressed in human non-cancerous esophageal mucosa and esophageal squamous cell carcinoma. We also examined whether LAT1 expression is correlated with histopathological features. METHODS: From January 1999 to December 2001, sections of formalin-fixed, paraffin-embedded tissue from 11 cases of early esophageal carcinoma (T1) and 19 cases of advanced esophageal carcinoma (T2, T3) were entered in the study. Histopathologically, all 30 cases were squamous cell carcinoma. Immunohistochemical staining was performed using rabbit anti-LAT1 IgG, with the standard avidin-streptavidin immuno-peroxidase method. Measurement was performed by means of computer-assisted image analysis. The ratio of cells with LAT1 expression in esophageal squamous cell carcinoma and non-cancerous esophageal mucosa was used for analysis in this study. RESULTS: Non-cancerous esophageal mucosa expressed LAT1 only in the basal layer of the esophageal wall. Esophageal squamous cell carcinoma expressed LAT1 throughout the tumor. LAT1 expression in esophageal squamous cell carcinoma was significantly higher than that in non-cancerous esophageal mucosa. LAT1 expression in esophageal squamous cell carcinoma increased as the depth of invasion progressed (T1 < T2 (P = 0.0477), T2 < T3 (P = 0.0415), T1 < T3 (P = 0.0044)), and as the tumor size increased. Also, high LAT1 expression was significantly associated with well-differentiated carcinoma. CONCLUSION: These results suggest that LAT1 plays a significant role in cell proliferation, differentiation, and invasion in esophageal squamous cell carcinoma.

Aged↗
PubMed2005

Monitoring expression of cytochrome P450 genes during postischemic rat liver reperfusion using DNA microarrays.

We investigated the expression of 50 cytochrome P450 (CYP) genes in the postischemic reperfused rat liver using a DNA microarray. Thirteen CYPs showed absent expression in all experiments and 2 CYPs were induced by pentobarbital, which was used as an anesthetic. Eight of the remaining 35 CYPs showed significantly decreased expression following ischemia-reperfusion. Monitoring CYP expression may be a powerful approach for elucidation of pathways regulating drug metabolism that may be involved in postischemic reperfusion liver injury.

Animals↗
PubMed2005

Molecular genetic alterations and gene expression profile of a malignant rhabdoid tumor of the kidney.

Malignant rhabdoid tumor of the kidney (MRTK) is a rare but highly aggressive tumor in children, and knowledge about the molecular signature of this tumor is limited. We report the molecular genetic alterations and gene expression profile of an MRTK tumor that arose in a 4-month-old Japanese girl. Fluorescence in situ hybridization and Southern blot analyses revealed a homozygous deletion of an approximately 0.29-Mb genomic region bordered by the Rgr and DDT genes in these tumor cells. This deleted region encodes SMARCB1, a candidate tumor suppressor gene for MRTK. Using a high-density oligonucleotide DNA array, we found increased expression of 25 genes, including genes involved in the cell cycle (10 genes), DNA replication (3 genes), cell growth (5 genes), and cell proliferation (5 genes), in this MRTK tumor sample, compared with a noncancerous kidney (NK) sample. On the other hand, 64 genes, including 4 genes regulating apoptosis, were found to show decreased expression in this MRTK tumor sample, compared with the NK sample. Among these alterations, we found alterations of expression of some genes, such as IGF2, MDK, TP53, and TNFSF10, in this MRTK tumor, as described previously. The molecular genetic alterations and altered pattern of gene expression found in this case may have contributed to the biological characteristics of the MRTK tumor that arose in our patient.

Apoptosis↗
PubMed2005

Ornithine breath test as a method to evaluate functional liver volume.

BACKGROUND: The purpose of this study was to investigate whether the functional liver volume can be measured from changes in expiratory 13CO2 levels after intravenous administration of L-[1, 2-13C] ornithine, using a rat model of hepatectomy. MATERIALS AND METHODS: Under pentobarbital anesthesia, 30%, 70%, or 90% hepatectomy was performed. In the control group, simple laparotomy was performed. Then, 20 mg/kg L-[1, 2-13C] ornithine was administered to rats via the femoral vein. A breath test was conducted 20 min after laparotomy. We examined the correlation of the sum of 13CO2 output (S) or a single point of 13CO2 level (SP) with liver weight/body weight (LW/BW) (%) every 15 min. RESULTS: In all of the groups, the ornithine breath test (OBT) graph reached a plateau level at about 6 min. The correlation coefficient between S15 and LW/BW was highest 0.952 (P <0.0001). The correlation coefficient between SP14 and LW/BW was highest, 0.944 (P <0.0001). The severity of hepatic injury could be evaluated, with significant differences in S5-15 and SP5-15 in all comparisons between groups. CONCLUSION: In the breath test with intravenously administered L-[1, 2-13C] ornithine, functional liver volume could be evaluated accurately in a short period.

Animals↗
PubMed2003

L-[1-13C] phenylalanine breath test reflects phenylalanine hydroxylase activity of the whole liver.

OBJECT: The purpose of this study was to perform L-[1-13C] phenylalanine breath test (PBT), measure phenylalanine hydroxylase (PAH) activity in liver tissue biopsies from patients, analyze the relationship between PBT results and PAH activity, and determine the time point at which measurements best reflect PAH activity in liver tissue. METHODS: PBT was performed in 25 patients (10 with normal liver and 15 with liver cirrhosis). After administering 10 mg/kg L-[1-13C] phenylalanine, 300 ml of expired air was collected over 90 min at 15-min intervals. The rate of hepatic phenylalanine oxidation (%13C dose h(-1)) at each time point was calculated from the amount of 13CO(2) in the breath, assuming a CO(2) production rate of 300 mmol m(-2) body surface area per hour. Subsequently, we examined the relationship between the results of PBT and PAH activity. RESULTS: PAH activity of the whole liver was significantly decreased in hepatic cirrhosis patients (P < 0.05). The results of PBT %13C dose h(-1) correlated with the PAH activity/liver, with correlation coefficients at 30, 45, and 60 min of more than 0.7, and the maximum correlation was at 30 min (r = 0.821, P < 0.0001). %13C cumulative excretion correlated with the PAH activity/liver with correlation coefficients of more than 0.7 after 45 min. The maximum correlation was at 90 min (r = 0.770, P = 0.001). CONCLUSION: PBT values reflect PAH activity in the whole liver and, in particular, the % dose h(-1) at 30 min after oral administration highly correlates with PAH activity, providing an important indicator for monitoring changes in whole liver PAH activity.

Adult↗
PubMed2003

Patients with severe liver cirrhosis followed up by L-[1-(13)C] phenylalanine breath test.

Compared to healthy subjects, patients with severe liver cirrhosis (LC) are reported to show lower values in the L-[1-(13)C] phenylalanine breath test (PBT). We performed this test several times during the clinical course in two patients with severe liver cirrhosis (LC). Patient 1 was a 67-year-old woman with non-B, non-C LC and hepatocellular carcinoma (HCC) in the lateral hepatic segment. Because the patient wanted to receive nonsurgical treatment for HCC, intraarterial administration of zinostatin stimalamer was performed. The patient was hospitalized four times before her death from liver failure on December 20, 2000. During her clinical course, PBT was performed four times. Values for both the rate of hepatic phenylalanine oxidation (%(13)C dose h(-1)) and %(13)C cumulative excretion gradually decreased during her clinical course. Patient 2 was a 57-year-old man with hepatitis C virus (HCV)-positive LC. He was hospitalized seven times between December 1998 and his death on May 24, 2001. During his clinical course, PBT was performed four times. Values for both %(13)C dose h(-1) and %(13)C cumulative excretion decreased during his clinical course. We confirmed that PBT was useful for following the course of LC.

Aged↗
PubMed2003

L-[1-13C] phenylalanine breath test reflects histological changes in the liver.

OBJECTIVE: Compared with healthy individuals, patients with chronic liver disease reportedly have lower L-[1-13C] phenylalanine breath test (PBT) values. However, there is no report detailing the relationship between the results of PBT and pathological data in liver disease patients. This study was designed to investigate the degree of histological changes in the liver that induce PBT changes and the time of measurement that reflects the histological change. MATERIALS AND METHODS: PBT was performed in 47 patients (10 with a normal liver, and 37 with chronic hepatitis C). After administering 10 mg/kg L-[1-13C] phenylalanine, 300 mL of expired air was collected over 90 min at 15-min intervals. The rate of hepatic phenylalanine oxidation (%13C dose h(-1)) at each time point was calculated from the amount of 13CO(2) in the exhaled air, assuming a CO(2) production rate of 300 mmol m(-2) body surface area per hour. Subsequently, we examined the relationship between the results of PBT and METAVIR pathological scoring. RESULTS: The highest correlation coefficients between the fibrosis score and %13C dose h(-1) and between the fibrosis score and %13C cumulative excretion were obtained at 45 min (r = -0.779, R(2) = 0.607; P < 0.0001) and 75 min (r = -0.768, R(2) = 0.590; P < 0.0001), respectively. CONCLUSION: PBT is a useful adjunct for detecting histological changes in the liver. The %13C dose h(-1) value at 45 min and the %13C cumulative excretion value at 75 min of PBT are useful for detecting hepatic histological change.

Biomarkers↗
PubMed2003

Transcriptional profiling in hepatoblastomas using high-density oligonucleotide DNA array.

Hepatoblastoma is a common hepatic tumor in children. Although evidence regarding cytogenetic and molecular genetic alterations in hepatoblastomas has been reported, the molecular events affecting the biologic characteristics of this tumor, including alterations of the gene expression profile, are largely unknown. To identify genes differentially expressed between nondiseased liver (NDL) and hepatoblastoma tumor (HBT), we analyzed the gene expression profile in 14 NDL and 16 HBT samples using a high-density oligonucleotide DNA array. Using Mann-Whitney U test followed by the k-nearest neighbor algorithm, we identified 26 genes (predictor genes) that were able to assign unknown samples derived from NDL and HBT to either the NDL group or HBT group with 100% accuracy. Using a cross-validation approach, we confirmed that the k-nearest neighbor algorithm assigned the particular samples derived from NDL and HBT to either the NDL or HBT group with 93.3% (28/30 samples) accuracy. In the 26 predictor genes, we found alteration of the expression of genes regulating cell division (NAP1L1, STMN1, CCNG2, and CDC7L1) and tumor cell growth (IGF2 and IGFBP4) in HBT. Four predictor genes (ETV3, TPR, CD34, and NR1I3) were also found to be mapped to the chromosomal region 1q21 approximately q32, which has been reported to be frequently involved in the development of hepatoblastoma. The findings obtained in this study suggest that alteration of the expression of some genes regulating cell division and tumor cell growth may be characteristics of the gene expression profile in HBT, and that alteration of the expression of the four predictor genes mapped to chromosomal region 1q21 approximately q32 may also contribute to the differences in gene expression profile between NDL and HBT.

Child↗
PubMed2003

Clinical application of oligonucleotide probe array for full-length gene sequencing of TP53 in colon cancer.

OBJECTIVE: TP53 mutations are the most frequent genetic alterations in colon cancer. We studied whether the recently developed oligonucleotide microarray technique, GeneChip p53 assay, can be applied to sensitive detection of TP53 gene mutations in surgical specimens from colon cancer patients. METHODS: TP53 gene mutations in exons 2-11 in 20 colon cancers and the corresponding histopathologically normal mucosa at the surgical margins were assessed by GeneChip p53 assay, and the results were further evaluated by direct sequencing of the involved exon or by mutant-allele-specific amplification (MASA). The expression of TP53 protein was also evaluated immunohistochemically and the result was compared with the gene alteration. RESULTS: The GeneChip p53 assay detected TP53 mutations in 65% of primary cancers; 61% of the mutations were within the evolutionarily conserved regions, and 46% of the mutations were within the zinc-binding domains (regions of loop 2 and loop 3). Direct sequencing confirmed these mutations. Immunohistochemical examination detected TP53 protein overexpression in 47% of primary cancers, but this protein did not accumulate with all types of TP53 mutations. In addition, the GeneChip assay detected a mutation identical to that in the primary tumor in 2 samples from the surgical margins, and MASA confirmed both mutations, implying the presence of occult cancer cells. CONCLUSION: The GeneChip p53 assay is sufficiently sensitive to detect TP53 mutations in surgical specimens from colon cancers and may be applicable to screening examination in clinical laboratories as a routine procedure.

Adult↗
PubMed2003

Localization of thioredoxin-interacting protein (TXNIP) mRNA in epithelium of human gastrointestinal tract.

Thioredoxin-interacting protein (TXNIP) is a negative regulator of thioredoxin. However, its role in the gastrointestinal (GI) epithelium is as yet unknown. Using in situ hybridization, we demonstrated that mRNA of TXNIP was differentially expressed in the epithelium of the human GI tract. TXNIP transcript was especially prominent in terminal differentiated cells. TXNIP was also highly expressed in lymphocytes in the lymphoid follicles. Our results suggest a new potential role of TXNIP in the differentiation of epithelial cells and in mucosal immunity of the GI tract.

Aged↗
PubMed2003

Profiling of genes differentially expressed between fetal liver and postnatal liver using high-density oligonucleotide DNA array.

The liver is an essential organ in humans not only for the production and storage of energy but also for detoxification of chemical compounds, but knowledge about changes in the gene expression profile in the human liver during the prenatal and postnatal periods is limited. Profiling of genes differentially expressed between the fetal liver (FL) and the postnatal liver (PNL) is one of the methods to investigate candidates affecting the difference in biological characteristics between FL and PNL. To identify genes differentially expressed between FL and PNL (childhood and adult liver), we analyzed the gene expression profiles across 9 FL and 14 PNL samples using a high-density oligonucleotide DNA array. Using Mann-Whitney U test followed by k-nearest-neighbors (supervised learning method) and hierarchical clustering (unsupervised learning method) algorithms, we found 33 genes clearly discriminating between the FL group and PNL group. The functional classification of the 33 genes identified was related to several kinds of biological pathways, regulating the cell cycle (PCNA, CDC7L1, CCND3, YWHA1, PKMYT1), DNA replication and repair (RFC4, RECQ2, PCNA, NAP1L1), cell growth (IGF2, IGFBP2, PRSS11), hormonal signals (AR, SRD5A1, NR1I3), and cellular metabolism (E2-EPF, WWP1, CYP2C9, CYP2E1, CYP2A6, CYP2A7, CYP2A13, CYP4F2, CYP3A4, DDT). The results presented herein provide evidence of a differential expression profile of genes regulating the cell cycle, DNA replication and repair, cell growth, regulation of hormonal signals, and cellular metabolism, between FL and PNL in humans. The 33 genes identified in this study are suggested to be useful markers clearly discriminating between FL and PNL using the gene expression profile.

Adult↗
PubMed2002

l-[1-(13)C]Alanine is a useful substance for the evaluation of liver function.

BACKGROUND: Using a rat model of hepatectomy, we investigated whether the severity of hepatopathy could be quantitatively measured from changes in expiratory (13)CO(2) levels after intravenous administration of l-[1-(13)C]alanine. MATERIALS AND METHODS: Under nembutal anesthesia, 20 mg/kg l-[1-(13)C]alanine was administered to rats via the femoral vein, and expiratory (13)CO(2) levels were measured for 15 min. Then, 30, 70, or 90% hepatectomy was performed. In the control group, simple laparotomy was performed. A breath test was conducted 20 min after laparotomy. We examined the correlation of total (13)CO(2) output (S) or single point (13)CO(2) level (SP) every 1 min for 15 min with liver weight/body weight (LW/BW) (%). RESULTS: In the control group, the breath test graph showed a specific peak level about 3 min after administration, but in all groups undergoing hepatectomy, it did not show any peak level during measurement. The correlation coefficient between S(12--15) after l-[1-(13)C]alanine administration and LW/BW was 0.902 (P < 0.0001). The correlation coefficient between SP(7) after l-[1-(13)C]alanine administration and LW/BW was highest, 0.908 (P < 0.0001). The severity of hepatopathy could also be evaluated, with significant differences in S(12-14) compared to control when the volume of resected liver was 30% or greater, but there was no significant difference between the groups undergoing 70 and 90% hepatectomy. However, the severity of hepatopathy could be evaluated, with significant differences in S(15) and SP(7) in all comparisons between groups. CONCLUSION: In the breath test with intravenously administered l-[1-(13)C]alanine, the severity of hepatopathy could be quantitatively evaluated in a short period by measuring S(15) and SP(7).

Alanine↗
PubMed2002

E-cadherin expression is inversely proportional to tumor size in experimental liver metastases.

OBJECTIVE: The role of E-cadherin in the metastatic process remains controversial. In this study, we examined what role E-cadherin plays in relation to tumor size and microvessel density (MVD) of the liver metastatic lesion. MATERIALS AND METHODS: In F344 male rats, metastatic lesions were made by injecting RCN-9 cells into the spleen. We performed an immunohistochemical evaluation of E-cadherin and MVD in the metastatic lesions. According to a previous report, we focused on tumor sizes ranging from 2 to 3 mm, and the metastatic nodules were divided into two groups considering the value of the MVD. RESULTS: The expression of E-cadherin was inversely proportional to tumor size (r = -0.882, P < 0.0001). MVD was directly proportional to metastatic tumor size (r = 0.726, P = 0.001). MVD in group A, in which the tumor size was 2.3 mm or more, was significantly higher than that in group B, in which the tumor size was less than 2.3 mm (3.13 +/- 1.65% vs 1.75 +/- 0.27%; P = 0.0069). The expression ratio of E-cadherin in group A was 28.21 +/- 16.36%, while it was 82.33 +/- 16.35% in group B (P = 0.0003). CONCLUSION: In liver metastasis, E-cadherin's function is preserved when the tumor is small and E-cadherin's expression is reduced in large tumors in which neovascularization is increased.

Animals↗
PubMed2002

Recovery of liver function in two-third partial hepatectomized rats evaluated by L-[1-13C]phenylalanine breath test.

BACKGROUND: We have previously reported that by means of a breath test with intravenously administered L-[1-13C] phenylalanine (13Cphe), hepatopathy could be quantitatively evaluated by measuring expiratory 13CO2 levels in a short period. It is known that phenylalanine hydroxylase activity (PAHA) plays an important role in phenylalanine metabolism. We examined the relationship between changes in PAHA and the results of the 13Cphe breath test during hepatic regeneration in a rat model of 70% hepatectomy, to assess their usefulness for evaluating hepatic regeneration. METHODS: Male Wistar rats (Shizvoka Laboratory Animal Center, Hamamatsu, Japan) weighing 230 to 290 g were subjected to 70% hepatectomy under anesthesia with sodium pentobarbital. One, 2, 3, 5, 7, and 14 days postoperatively, 30 mg/kg 13Cphe was intravenously injected into the femoral vein, and the increase in exhaled 13CO2 (Delta 13CO2) was measured for 15 minutes. Simple laparotomy was performed in control rats. After the breath test, the regenerated liver was removed and weighed. The amount of DNA, amount of hepatic tissue total protein (TP), and PAHA were determined. RESULTS: The r between liver weight/body weight and PAHA, between DNA and PAHA, and between TP and PAHA were 0.832, 0.720, and 0.758, respectively. Breath test graphs revealed that liver weight/body weight, DNA, and TP showed the best correlations with the peak value of Delta 13CO2 (liver weight/body weight percentage, r = 0.801; DNA, r = 0.660; TP, r = 0.706), and r between PAHA and peak value was 0.638. CONCLUSIONS: These results suggest that measurement of PAHA in regenerated liver is an effective method for following up liver function after hepatic resection. Moreover, the 13Cphe breath test may also be useful to evaluate liver function after partial hepatectomy.

Animals↗