Publications (43) View all
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Article: Tumor-derived Tenascin-C Promotes the Epithelial-Mesenchymal Transition in Colorectal Cancer Cells.
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ABSTRACT: Tenascin-C (TNC) is an extracellular matrix glycoprotein, usually derived from myofibroblasts in the cancer microenvironment. Recently, however, the significance of tumor-derived TNC in initiation of cancer metastasis was disclosed. We investigated the clinical significance of cancer-derived TNC in colorectal cancer (CRC) cases. TNC expression in 170 cases of CRC was analyzed by quantitative real-time polymerase chain reaction (PCR). In addition, gene expression arrays using purely-separated cancer tissues of another 86 cases was performed and the functional implications of cancer-specific TNC were investigated. The expression of TNC mRNA was significantly higher in CRC tissues than in the corresponding normal tissues. Cancer cell-specific TNC expression was a significant prognostic factor in CRC cases. Moreover, cancer cell-derived TNC was associated with the epithelial-mesenchymal transition (EMT) signature. Cancer cell-derived TNC promotes cancer invasiveness via EMT regulation, and not cancer tissue TNC but cancer cell-specific TNC is a novel indicator of poor prognosis.Anticancer research 05/2013; 33(5):1927-34. · 1.73 Impact Factor -
Article: Clinical Significance of PICT1 in Patients of Hepatocellular Carcinoma with Wild-Type TP53.
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ABSTRACT: BACKGROUND: TP53 is one of the most widely known cancer suppressor genes. Mutations in TP53 are ubiquitously observed in almost all cancers. Incidences of mutations range from ~15-70 % in patients with hepatocellular carcinoma (HCC). Moreover, patients with mutated TP53 have poorer prognoses than those with wild-type TP53; therefore, it would be beneficial to predict the prognosis of HCC patients with wild-type TP53. We previously reported that PICT1, coding a nucleolus protein, regulates TP53 through indirect association. METHODS: In this study, we examined PICT1 expression levels and the status of TP53 in 51 primary HCC tissues in order to determine the clinical significance of PICT1 expression and the function of PICT1 in HCC cells. RESULTS: We detected 6 mutations in the 51 samples. In 45 patients with wild-type TP53, those with high PICT1 expression (n = 11) had poorer prognoses than those with low PICT1 expression (n = 34), and there were no significant associations with other clinicopathological factors. According to gene set enrichment analysis, PICT1 expression was inversely correlated with the gene set of TP53. In vitro assays indicated that suppression of PICT1 expression caused an increase in TP53 expression, reduction in cell proliferation, and arrest at the G1 phase of the cell cycle in HCC cells expressing wild-type TP53. CONCLUSIONS: PICT1 should be a useful prognostic marker in HCC patients having wild-type TP53. Furthermore, PICT1 may become a promising therapeutic target because of its ability to increase the expression and activation of TP53.Annals of Surgical Oncology 03/2013; · 4.17 Impact Factor -
Article: Plastin3 is a novel marker for circulating tumor cells undergoing the epithelial-mesenchymal transition and is associated with colorectal cancer prognosis.
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ABSTRACT: Circulating tumor cells (CTCs) in the blood have attracted attention as biomarkers and seeds of metastasis. However, systems that detect CTC on the basis of epithelial markers (e.g., EpCAM, cytokeratins) may miss many tumor cells as a result of marker downregulation after epithelial-mesenchymal transition (EMT). The purpose of this study was to define CTC-based prognostic markers in colorectal cancer that are not repressed by EMT. Here we report Plastin3 (PLS3) as a novel CTC marker associated with with invasive and metastatic capabilities of colorectal cancer cells. Employing a qRT-PCR assay specific for PLS3, peripheral blood samples of CRC patients were analyzed (training set, n = 381; validation set, n = 330). PLS3 was not expressed by normal blood cells. Its expression was high in metastatic CRC cells and it was not downregulated during EMT. Detection of PLS3-positive CTC in peripheral blood was associated with reduced overall patient survival. Multivariate analysis showed that this prognostic influence was independent from established risk factors. In particular, in Dukes grade B and C patients, detection of PLS3-positive CTC was determined to be the most significant prognostic factor, surpassing other currently available clinicopathological factors. Our results firmly establish PLS3 as a novel marker for the detection of metastatic CRC cells in the blood, offering a significant value compared to other known prognostic factors.Cancer Research 02/2013; · 7.86 Impact Factor -
Article: Clinical significance of the expression of long non-coding RNA HOTAIR in primary hepatocellular carcinoma.
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ABSTRACT: The functions of many long non-coding RNAs (ncRNAs) in human cancers have not yet been elucidated. The long ncRNA HOTAIR is expressed from the developmental HOXC locus located on chromosome 12q13.13. Previous reports have demonstrated that HOTAIR associates with chromatin modifications in cooperation with the Polycomb complex PRC2, and promotes breast and colorectal cancer metastasis. In this study, we examined the clinical significance of HOTAIR expression in patients with hepatocellular carcinoma (HCC). HOTAIR expression was detected in primary HCCs in 13 out of 64 patients. Patients with HOTAIR expression had significantly poorer prognoses and a larger primary tumor size than those without HOTAIR expression, similar to studies in breast and colorectal cancers. Moreover, introduction of human HOTAIR into liver cancer cells revealed that HOTAIR promoted more rapid proliferation compared to control cells. Thus, although the clinical significance of HOTAIR expression in HCC may not be as pronounced as that in breast and colorectal cancers, the current study demonstrates that HOTAIR expression is associated with HCC progression, warranting further studies.Oncology Reports 12/2012; · 1.84 Impact Factor -
Article: [Usefulness of esophageal stenting for esophagorespiratory fistula with esophageal cancer].
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ABSTRACT: We evaluated the outcome of esophageal stenting for esophagorespiratory fistula in patients with advanced esophageal cancer. Six patients with such fistula underwent esophageal stenting at our department from January 2000 to May 2012. Intraoral ingestion improved in all patients. Cough decreased immediately after stenting in 3 patients, and pneumonia detected by chest radiography improved within 1 week in 2 patients. Ventilation was weaned 2 days after stenting in 1 patient. The median survival duration after stenting was 31 days, and the cause of death was cancer in all patients. The following background factors were identified at the time of death: bleeding(n=3), mediastinitis(n=1), and pneumonia(n=1). Esophageal stenting, which should always be performed with the informed consent of the patient, improves respiratory symptoms, intraoral ingestion, and quality of life. Therefore, it is one of the best palliative therapies for patients with esophagorespiratory fistula associated with advanced esophageal cancer.Gan to kagaku ryoho. Cancer & chemotherapy 11/2012; 39(12):1849-51.
