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Yoshiyuki Kuwabara

Publications and source records attributed to Yoshiyuki Kuwabara.

16 recordsLinked to original sources
PubMed2007

A novel gene, RSRC2, inhibits cell proliferation and affects survival in esophageal cancer patients.

In Japan and China, esophageal cancer is common and more than 90% of esophageal cancers are squamous cell carcinoma. Esophageal squamous cell carcinoma (ESCC) shows a poor prognosis, but the mechanism of ESCC and target genes for treatment remains unclear. We searched for genes related to ESCC, and identified a novel gene, FLJ11021, which was designated arginine/serine-rich coiled-coil 2 (RSRC2). We sought to determine the role of RSRC2 in the proliferation of esophageal cell lines and to examine the relationship between RSRC2 and clinicopathologic factors and ESCC prognosis. Expression of RSRC2 was quantified by real-time reverse transcription polymerase chain reaction (RT-PCR) in 70 primary ESCCs and paired noncancerous esophageal mucosa. To determine the role of RSRC2 in ESCC cell proliferation, we used vector-based transfection and small interfering RNA methods. Our results show that RSRC2mRNA levels in all ESCC cell lines (TE1-15, excluding TE7) were lower than those in a human esophageal squamous epithelial cell line (Het-1A). Cell proliferation of an ESCC cell line was inhibited by overexpression of RSRC2, while reduced expression was accompanied by tumor progression. RSRC2 expression levels were significantly correlated with depth of invasion, lymph node metastasis, lymphatic invasion and vascular invasion. Moreover, ESCC patients with low RSRC2mRNA expression had significantly shorter post-operative survival time than those with high expression. In vitro study revealed that RSRC2 might play a role in cell proliferation. Our study demonstrated that RSRC2 expression may be a novel tumor suppressor of esophageal cancer cell growth and a prognostic factor in ESCC.

Aged↗
PubMed2006

RNASEN regulates cell proliferation and affects survival in esophageal cancer patients.

PURPOSE: MicroRNAs (miRNA) are small noncoding RNAs thought to be involved in physiologic and developmental processes by negatively regulating the expression of target genes. Little is known about the role of miRNAs in normal and cancer cells. It is possible that deregulation of miRNA may contribute to the oncogenesis of some cancers. We studied the expression level of the miRNA processing enzyme (DICER1, DGCR8, and RNASEN) in esophageal squamous cell carcinoma (ESCC). EXPERIMENTAL DESIGN: The expression levels of DICER1, DGCR8, and RNASEN mRNA in 73 ESCC tissues were compared with that in corresponding normal esophageal epithelium by Taqman real-time reverse-transcription PCR. We also examined RNASEN protein expression in 27 cell lines. The role of RNASEN in cell proliferation in ESCC cells was assessed by small interfering RNA. Paraffin sections of ESCC patients were immunohistochemically investigated. RESULTS: We found that RNASEN expression levels were enhanced in a fraction of esophageal cancers. Multivariate Cox regression analysis showed that the prognostic effect of RNASEN (P = 0.0036) seems to be independent of disease stage (P = 0.0060). Knockdown of RNASEN in esophageal cancer cell lines resulted in a 46% to 85% reduction in cell number. In an immunohistochemical study, the intensity of RNASEN expression was often increased in the tumor compared with that in normal epithelium. CONCLUSIONS: The relationship between the RNASEN expression and the prognosis of the ESCC patients warrants a further study on the role of miRNA and tumor progression.

Adult↗
PubMed2006

Expression and prognostic roles of PABPC1 in esophageal cancer: correlation with tumor progression and postoperative survival.

The prognosis of patients with esophageal cancer remains poor. TNM classification is not sufficient to predict their prognosis, and novel predictive markers of the prognosis of esophageal cancer patients are therefore needed. Poly A binding protein, cytoplasmic 1 (PABPC1) plays a role in post-transcriptional control of mRNA and may be involved in tumorigenesis. PABPC1 expression has not been studied in esophageal cancer. Expression of PABPC1 was quantified by real-time reverse transcription polymerase chain reaction (RT-PCR) using LightCycler in 41 primary esophageal squamous cell carcinomas (ESCCs) and their paired normal esophageal mucosa. We examined the correlation between PABPC1 expression and the clinicopathological factors and prognosis of ESCC patients. Reduced expression of PABPC1 was accompanied by locally invasive tumors (t-factor, p=0.0145) and more advanced tumors (pathologic stage, p=0.0264). Moreover, ESCC patients with low PABPC1 mRNA expression had a significantly shorter postoperative survival time than those with high expression (median survival, 3.1 vs. 6.5 months, p=0.002). In esophageal cancer, reduced expression of PABPC1 was correlated with local tumor progression and poor prognosis after surgery.

Aged↗
PubMed2006

Expression of ACP6 is an independent prognostic factor for poor survival in patients with esophageal squamous cell carcinoma.

ACP6 (acid phosphatase 6, lysophosphatidic) is a lysophosphatidic acid (LPA)-specific phosphatase that hydrolyzes LPA to monoacylglycerol and is involved in lipid metabolism in the mitochondria. Its role in oncogenesis and cancer progression has not been studied. In this study, we examined the expression of ACP6 mRNA and evaluated its clinical significance in esophageal squamous cell carcinoma (ESCC). Expression of ACP6 mRNA was quantified by real-time reverse transcription polymerase chain reaction using the LightCycler in 70 esophageal ESCC specimens and their paired normal esophageal mucosa. The data were analyzed with reference to clinicopathological factors. ACP6 mRNA expression in esophageal cancer tissue was significantly lower than that in corresponding normal esophageal mucosa (P=0.0301). Among the esophageal cancer tissues, ACP6 mRNA expression significantly correlated with local tumor invasion (T factor, P=0.0461) and lymph node metastasis (P=0.0128). Furthermore, low ACP6 mRNA expression was associated with a significantly shorter survival time compared with high expression (log-rank test, P=0.0358). In multivariate analysis, ACP6 mRNA expression emerged as a significant independent factor (P=0.0148). Impaired ACP6 expression may lead to more aggressive invasion of ESCC, and ACP6 mRNA expression level could be an independent prognostic factor for patients with ESCC.

Aged↗
PubMed2005

Epidermal growth factor receptor gene mutation in non-small cell lung cancer using highly sensitive and fast TaqMan PCR assay.

Epidermal growth factor receptor (EGFR) gene mutations have been found in a subset of non-small cell lung cancer (NSCLC) with good clinical response to gefitinib therapy. A quick and sensitive method with large throughput is required to utilize the information to determine whether the molecular targeted therapy should be applied for the particular NSCLC patients. Using probes for the 13 different mutations including 11 that have already been reported, we have genotyped the EGFR mutation status in 94 NSCLC patients using the TaqMan PCR assay. We have also genotyped the EGFR mutations status in additional 182 NSCLC patients, as well as 63 gastric, 95 esophagus and 70 colon carcinoma patients. In 94 NSCLC samples, the result of the TaqMan PCR assay perfectly matched with that of the sequencing excluding one patient. In one sample in which no EGFR mutation was detected by direct sequencing, the TaqMan PCR assay detected a mutation. This patient was a gefitinib responder. In a serial dilution study, the assay could detect a mutant sample diluted in 1/10 with a wild-type sample. Of 182 NSCLC samples, 46 mutations were detected. EGFR mutation was significantly correlated with gender, smoking status, pathological subtypes, and differentiation of lung cancers. There was no mutation detected by the TaqMan PCR assay in gastric, esophagus and colon carcinomas. TaqMan PCR assay is a rapid and sensitive method of detection of EGFR mutations with high throughput, and may be useful to determine whether gefitinib should be offered for the treatment of NSCLC patients. The TaqMan PCR assay can offer us a complementary and confirmative test.

Adolescent↗
PubMed2004

Lung injury after intestinal ischemia-reperfusion may be avoided by the reduced absorption of locally produced cytokines.

PURPOSE: It has been suggested that inflammatory mediators such as cytokines released during intestinal ischemia and reperfusion increase permeability in the lungs. Cytokines exist at concentrations several hundred times higher at the site of inflammation than in the blood. When absorbed, the locally produced cytokines may affect multiple remote organs. We thus investigated whether the isolation of the intestine in a bag during ischemia and reperfusion can reduce subsequent lung injury. METHODS: Rats were divided into three groups: group 1, simple laparotomy (sham); group 2, intestinal ischemia and reperfusion (I/R); and group 3, intestinal ischemia and reperfusion with an intestinal bag (IB). Lung permeability was assessed using the Evans Blue leakage method. Cytokines (interleukin-1beta, tumor necrosis factor alpha, interleukin-8) in the plasma and ascites were measured by enzyme-linked immunosorbent assay. RESULTS: The increase in lung permeability of I/R significantly decreased in IB (1.73 +/- 0.48 vs 1.05 +/- 0.22, P < 0.01). The plasma cytokine concentrations were also lower in IB than in I/R. In addition, the cytokine levels in the intestinal bag fluid were extremely high. CONCLUSION: The isolation of the intestine during ischemia and reperfusion was found to reduce the degree of subsequent lung injury, possibly due to the reduced absorption of locally produced cytokines via the parietal peritoneum.

Analysis of Variance↗
PubMed2004

Excision repair cross complementing 3 expression is involved in patient prognosis and tumor progression in esophageal cancer.

The prognosis of patients with esophageal cancer remains poor. TNM classification is not sufficient to predict the prognosis. Therefore, novel predictive markers of the prognosis of esophageal cancer patients are awaited. The abnormality of the nucleotide excision repair (NER) is often involved in human cancers. Excision repair cross complementing 3 (ERCC3) contributes to NER. In esophageal cancer, ERCC3 expression has not been studied. Expression of ERCC3 was quantified by real-time reverse transcription polymerase chain reaction (RT-PCR) using LightCycler in 43 primary esophageal squamous cell carcinomas (ESCCs) and their paired normal esophageal mucosa. We examined the correlation between the ERCC3 expression and the clinicopathological factors and prognosis of ESCC patients. ERCC3 expression level was significantly correlated with the pathologic stage, tumor size and local invasiveness (t-factor) in esophageal cancer tissues. Reduced expression of ERCC3 was accompanied with tumor progression (p=0.0049) and higher pathologic stage (p=0.020). Moreover, ESCC patients with low ERCC3 mRNA expression had significantly shorter post-operative survival time than those with high expression (p=0.0003). In esophageal cancer, reduced expression of ERCC3 was correlated with local tumor progression and poor prognosis after operation.

Aged↗
PubMed2003

Real-time energy metabolism of intestine during arterial versus venous occlusion in the rat.

BACKGROUND: Although it is less frequently encountered, mesenteric vein occlusion poses as important a problem as mesenteric artery occlusion. The energy metabolism of intestinal tissue during venous occlusion and reperfusion was studied. METHODS: Male Wistar rats were studied in four groups of 17 animals each. Intestinal ischemia was induced by clamping the superior mesenteric artery ([SMA] occlusion [O]) or vein (SMVO) for 30 or 60 min, followed by reperfusion. Magnetic resonance spectroscopy was employed to continuously monitor the energy metabolism. Additionally, intestinal motility was monitored and histological examination was performed on resected specimens. RESULTS: Energy metabolism in SMVO during ischemia was reduced more slowly than in SMAO, but recovery after reperfusion was poorer in SMVO. During ischemia, the contractive response of the intestine lasted longer in SMVO than in SMAO. Histologically, mucosal and subserosal hemorrhage was more severe in SMVO. CONCLUSIONS: In contrast to SMAO, SMVO caused less severe reduction of energy metabolism, at the expense of hemorrhage and tissue damage.

Animals↗
PubMed2002

Decreased expression of DFF45/ICAD is correlated with a poor prognosis in patients with esophageal carcinoma.

BACKGROUND: DNA fragmentation factor 45 (DFF45)/inhibotor of caspase activated DNAse (ICAD) forms a complex with DFF40/CAD and inhibits its DNA cleaving function during apoptosis. DFF45 also functions as a chaperone for native DFF40 and is necessary for its function. It has been indicated that defects in the apoptotic pathway may exist in neoplastic cells. METHODS: The authors investigated mRNA expression of DFF45 in a series of 46 esophageal squamous cell carcinoma (ESCC) specimens using polymerase chain reaction amplification. The results were correlated with the patients' clinicopathologic characteristics. RESULTS: DFF45 mRNA expression was significantly lower in tumors with higher pathologic stage, higher tumor status (T status), lymph node metastasis, or more extensive lymphatic invasion. Patients who had low DFF45 mRNA expression (indicated by the ratio of DFF45 mRNA expression in tumor to DFF45 mRNA expression in normal esophageal mucosa [tumor:normal] < 1) had a significantly shorter survival after undergoing surgery compared with patients who had high DFF45 mRNA expression (tumor:normal > 1, P = 0.0006; log-rank test, P = 0.0003; median follow-up, 14.6 months). CONCLUSIONS: Patients with ESCC with decreased DFF45 mRNA expression levels had a poor prognosis compared with patients who had high DFF45 mRNA expression levels.

Aged↗
PubMed2002

Telomerase activity in esophageal squamous cell carcinoma: down-regulation by chemotherapeutic agent.

BACKGROUND AND OBJECTIVES: Telomerase has been suggested as being necessary for continued cell growth and progression of cancer. Esophageal cancer and matched normal esophageal tissue from 54 patients were analyzed for telomerase activity, human telomerase reverse transcriptase (hTERT) mRNA expression, and their correlation with clinicopathological factors. METHODS: Telomeric repeat amplification protocol was used for detection of telomerase activity and real time quantitative RT-PCR was used for hTERT mRNA. An esophageal carcinoma cell line was used to study the effect of chemotherapeutic agent on telomerase. RESULTS: Telomerase activity was detectable in 79.6% of the tumor and 59.3% of the normal esophageal tissue. The level of telomerase activity in the tumor was significantly higher than that in the normal tissue. A significantly higher telomerase activity was observed in tumors with extensive blood vessel invasion. A significantly lower telomerase activity was observed in tumors that showed good response to preoperative chemotherapy than those with poor response. TE-9 cells exposed to 5-FU showed a diminished telomerase activity preceded by a time-dependent decrease in the mRNA expression of hTERT. CONCLUSIONS: Telomerase activity was high in esophageal cancer tissue and showed positive correlation with blood vessel invasion. Chemotherapeutic agents may down-regulate telomerase activity.

Aged↗
PubMed2002

Role of matrix metalloproteinase-9 in in vitro invasion of esophageal carcinoma cells.

BACKGROUND AND OBJECTIVES: Although some investigators recently suggested that MMP-9 may play a critical role in invasion and metastasis, along with MMP-2, in esophageal carcinoma, there has been no direct evidence that MMPs play a critical role in the actual invasion of esophageal carcinoma cells. Here, we investigated the role of MMPs in the in vitro invasion of esophageal carcinoma cell lines (TE-series). METHODS: Our methods included in vitro invasion assay, gelatin zymography, and enzyme-linked immunosorbent assay (ELISA). RESULTS: Four cell lines (but not TE-5) secreted MMP-2 and MMP-9 in the culture medium. Using a quantitative in vitro invasion assay, we found a significant (P = 0.002) correlation between the extent of in vitro invasion and the amount of MMP-9, but not of MMP-2, secreted into the conditioned medium in the four cell lines. In these cell lines, R-94138, a specific MMP-9 inhibitor, inhibited in vitro invasion in a dose-dependent manner. Although TE-5 did not secrete MMP-2 or MMP-9, the cells showed a strong in vitro invasion. CONCLUSIONS: Our data suggest that most of the esophageal carcinoma cell lines use MMP-9 for in vitro invasion, but others may use proteinase(s) other than MMP-9.

Carcinoma, Squamous Cell↗
PubMed2002

The effectiveness of palliative resection for advanced esophageal carcinoma: analysis of 24 consecutive cases.

PURPOSE: In some patients who already have advanced esophageal cancer at the time of presentation, symptoms like the inability to eat, and complications such as bronchoesophageal fistula are so debilitating that palliative resection may be beneficial. However, resection of the esophagus is associated with significant risk, and whether this operation should be performed for palliation remains controversial. Because few reports have been published on this subject, we retrospectively analyzed 24 patients with esophageal cancer who underwent palliative resection. METHODS: Esophageal resection was performed with palliative intent in 12 patients and with curative intent in another 12 who were left with residual cancer. RESULTS: There was no operative death. All of the ten patients who had been unable to eat preoperatively were able to eat after the operation, and four patients with a life-threatening bronchoesophageal fistula were free of symptoms after the operation. Two patients died in hospital during the postoperative chemotherapy but the other 22 were discharged. The mean survival period was 264 days. CONCLUSIONS: With improved postoperative care, the risk of palliative esophageal resection is no longer considered unacceptable.

Adult↗
PubMed2002

Chfr expression is downregulated by CpG island hypermethylation in esophageal cancer.

Cell cycle progression is monitored by checkpoint mechanisms to ensure the integrity of the genome and the fidelity of sister chromatid separation. Failure of such checkpoint functions results in genomic instability, a condition that predisposes cells to neoplastic transformation and tumor progression. Recently, Scolnick and Halazonetis defined a new mitotic checkpoint that acts at prophase and delays chromosome condensation in response to mitotic stress, and identified a gene, named checkpoint with FHA and ring finger (Chfr), that seems to be required for delaying prophase in human cells. In the present study, we examined human Chfr mRNA expression in 15 human esophageal cancer cell lines and 43 primary esophageal cancers to investigate the potential involvement of Chfr in the pathogenesis of esophageal cancers. We report here that a significant proportion of human esophageal cancer has loss of expression of Chfr gene. Furthermore, we found aberrant hypermethylation of the promoter region of this checkpoint gene in four of 15 (26.7%) esophageal cancer cell lines and in seven of 43 (16.3%) primary cancers.

Adenocarcinoma↗
PubMed2002

Decreased peroxisome proliferator-activated receptor gamma gene expression is correlated with poor prognosis in patients with esophageal cancer.

BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPAR gamma) induces apoptosis by ligand stimulation in various tumor cell lines. In esophageal cancer cell lines, PPAR gamma activation also has suppressed the proliferation. METHODS: In 55 primary esophageal squamous cell carcinomas (ESCCs) we examined the correlation between the expression of PPAR gamma mRNA with prognosis of esophageal cancer patients. The expression of PPAR gamma mRNA was quantified by real-time reverse transcription polymerase chain reaction using LightCycler. Immunohistochemistry was used to study the expression of PPAR gamma protein. RESULTS: The expression of PPAR gamma mRNA was significantly decreased in esophageal cancer cells compared with normal esophageal mucosa (P = 0.0084). Among the clinical factors, PPAR gamma mRNA expression was lower in the tumors with extensive lymph node metastasis (n4) than those with less extensive lymph node metastasis (n0-3) (P = 0.0059). Patients with low PPAR gamma mRNA expression had significantly shorter postoperative survival time than those with high PPAR gamma mRNA expression (P = 0.0191). In immunohistochemistry, PPAR gamma protein was expressed in the nuclei of cells in some cases and expressed in the nuclei and cytoplasm in others. The expression of PPAR gamma protein is decreased in esophageal cancer tissue compared with normal esophageal squamous epithelium. However, we could not deduce the apparent relation for the expression between PPAR gamma mRNA and PPAR gamma proteins in immunohistochemistry (P = 0.284). CONCLUSIONS: In esophageal cancer tissues, the expression of PPAR gamma was decreased compared with normal esophageal epithelium. The mRNA expression level of PPAR gamma may be a marker of prognosis after operation in esophageal cancer patients.

Esophageal Neoplasms↗
PubMed2002

Expression of PTTG (pituitary tumor transforming gene) in esophageal cancer.

BACKGROUND: Recently, a vertebrate securin [pituitary tumor transforming gene (PTTG) in humans] has been identified that inhibits sister chromatid separation and is involved in malignant transformation and tumorigenesis. Abundance of this protein would disrupt cell division, generate chromosomal instability and thereby increase cell susceptibility to acquisition of further mutations during subsequent division. Esophageal cancer is a disease with poor prognosis with early local invasion and lymph node metastasis. It is important to identify factors that influence the aggressiveness of esophageal cancer. METHODS: Expression of PTTG messenger ribonucleic acid (mRNA) was evaluated by real-time reverse transcription polymerase chain reaction in 48 esophageal cancer specimens and matched normal esophageal mucosa. The data were analyzed with reference to clinicopathological factors. RESULTS: Tumor tissue expressed a significantly higher level of PTTG1 mRNA than the corresponding normal tissue (P < 0.0001). PTTG1 mRNA expression was significantly higher in tumors with higher pathological stage (IV vs 0-III, P = 0.0442) or more extensive lymph node metastasis (pathological N factor; N4 vs N0-3, P = 0.003). The median survival for patients with high PTTG1 expression (8.5 months) was less than that for patients with low PTTG1 expression (14.0 months, P = 0.039). PTTG1 expression was one of the significant predictors of survival on univariate analysis (hazard ratio 2.225; 95% confidence interval 1.007-4.915). CONCLUSIONS: Detection of high PTTG1 expression in surgically excised esophagus tumor tissues might help to identify patients with aggressive disease who require adjuvant therapy and provide prognostic information.

Aged↗