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Hideki Yokoo

Publications and source records attributed to Hideki Yokoo.

8 recordsLinked to original sources

Database of two-dimensional polyacrylamide gel electrophoresis of proteins labeled with CyDye DIGE Fluor saturation dye.

CyDye DIGE Fluor saturation dye (saturation dye, GE Healthcare Amersham Biosciences) enables highly sensitive 2-D PAGE. As the dye reacts with all reduced cysteine thiols, 2-D PAGE can be performed with a lower amount of protein, compared with CyDye DIGE Fluor minimal dye (GE Healthcare Amersham Biosciences), the sensitivity of which is equivalent to that of silver staining. We constructed a 2-D map of the saturation dye-labeled proteins of a liver cancer cell line (HepG2) and identified by MS 92 proteins corresponding to 123 protein spots. Functional classification revealed that the identified proteins had chaperone, protein binding, nucleotide binding, metal ion binding, isomerase activity, and motor activity. The functional distribution and the cysteine contents of the proteins were similar to those in the most comprehensive 2-D database of hepatoma cells (Seow et al.., Electrophoresis 2000, 21, 1787-1813), where silver staining was used for protein visualization. Hierarchical clustering on the basis of the quantitative expression profiles of the 123 characterized spots labeled with two charge- and mass-matched saturation dyes (Cy3 and Cy5) discriminated between nine hepatocellular carcinoma cell lines and primary cultured hepatocytes from five individuals, suggesting the utility of saturation dye and our database for proteomic studies of liver cancer.

Cell Line, Tumor↗

Pulmonary resection for metastases from hepatocellular carcinoma: factors influencing prognosis.

OBJECTIVE: Although the lung is the most common site of extrahepatic spread from hepatocellular carcinoma, outcomes after pulmonary resection and prognostic factors have not been well described. We analyzed a single-center experience with 25 patients undergoing pulmonary resection of metastases from hepatocellular carcinoma to examine the clinical factors and outcomes. METHODS: Patients were candidates for resection if they had controlled intrahepatic disease with no evidence of extrathoracic lesions and if all gross tumors could be removed with preservation of respiratory function. Twenty-five patients with hepatocellular carcinoma who underwent curative hepatectomy were suitable for the pulmonary resection criteria between 1990 and 2005. Clinical features and outcomes were analyzed. RESULTS: The mean actuarial 1-, 3-, and 5-year survivals after pulmonary resection were 80%, 61%, and 36%, respectively. Tumor number (solitary or multiple) and location (unilateral or bilateral lung) did not significantly affect cancer-specific survival. Mean 5-year survival was 25% for patients with disease-free interval of 1 to 11 months and 62% for those with disease-free interval of 12 months or more. Mean survival was 15.9 months for patients with alpha-fetoprotein of 500 ng/mL or more, and 39.2 months for those with alpha-fetoprotein less than 500 ng/mL. Five-year survival was 21% for patients with short disease-free interval or high alpha-fetoprotein level and 74% for those with long disease-free interval and low alpha-fetoprotein level (P = .015). CONCLUSION: Pulmonary resection for metastases from hepatocellular carcinoma may prolong survival in selected patients. Disease-free interval greater than 12 months and alpha-fetoprotein less than 500 ng/mL are important prognostic factors.

Adult↗

Proteomic study of human hepatocellular carcinoma using two-dimensional difference gel electrophoresis with saturation cysteine dye.

To identify the proteomic alterations associated with carcinogenesis of hepatocellular carcinoma (HCC), we compared the protein expression profiles of nine HCC cell lines with those of primary cultured hepatocytes established from five individuals. A differential proteomic study was performed by two-dimensional difference gel electrophoresis, in which protein samples are labeled with different fluorescent dyes and separated according to their isoelectric point and molecular weight. To label the protein samples, we used a newly developed and highly sensitive fluorescent dye, which reacts with all reduced cysteine residues of proteins. Principal component analysis based on the intensity of 1238 protein spots indicated that the HCC cells and the normal hepatocytes had distinct proteomic profiles. The Wilcoxon test was used to determine the protein spots whose intensity was differentially regulated in the HCC cells compared with the normal hepatocytes, and mass spectrometric analysis was used to identify the proteins corresponding to the spots. The proteins identified are involved in cell cycle regulation, binding to a tumor-suppressor gene product, fatty acid binding, and regulation of translation. Western blotting with specific antibodies revealed the overexpression of PCNA, EB1 and E-FABP in HCC tissues compared with noncancerous tissues. Aberrant regulation of EB1 and E-FABP has not previously been implicated in the development of HCC.

Adult↗

Protein expression pattern distinguishes different lymphoid neoplasms.

To identify proteins associated with the histological subtypes of lymphoid neoplasms, we studied the proteomes of 42 cell lines from human lymphoid neoplasms including Hodgkin's lymphoma (HL; four cell lines), B cell malignancies (19 cell lines), T cell malignancies (16 cell lines), and natural killer (NK) cell lymphoma (three cell lines). The protein spots were sequentially selected by (i) Wilcoxon or Kruskal-Wallis tests to find the spots whose intensity was significantly (p <0.05) different among the cell line groups, (ii) by statistical-learning methods to prioritize the spots according to their contribution to the classification, and (iii) by unsupervised classification methods to validate the classification robustness by the selected spots. The selected spots discriminated (i) between HL cells and other cells, (ii) between the cells from B cell malignancies, T cell malignancies, and NK cell lymphoma cells, and (iii) between HL cells and anaplastic large cell lymphoma cells. Among the 31 informative protein spots, MS identified 24 proteins corresponding to 23 spots. Previous reports did not correlate these proteins to lymphocyte differentiation, suggesting that a proteomic study would identify the novel mechanisms responsible for the histogenesis of lymphoid neoplasms. These proteins may have potential as differential diagnostic markers for lymphoid neoplasms.

Amino Acid Sequence↗

Proteomic signature corresponding to alpha fetoprotein expression in liver cancer cells.

Alpha fetoprotein (AFP) has been implicated in the development of hepatocellular carcinoma and is considered to be a diagnostic and prognostic tumor marker. Because elevated expression of AFP is associated with many characteristics of hepatocellular carcinoma tissues, we hypothesized that multiple proteins may function in a coordinated manner with AFP. To identify such proteins, we performed global protein expression analysis, namely a proteomic study. The protein expression profiles of 9 AFP-producing liver cancer cell lines (JHH-5, HuH-1, PLC/PRL/5, Hep3B, HT-17, JHH-7, HuH-7, HepG2, Li-7) and 7 nonproducing liver cancer cell lines (HLE, JHH-6, Sk-Hep-1, JHH-4, HLF, RBE, SSP-25) were generated by fluorescence 2-dimensional difference gel electrophoresis. In fluorescence 2-dimensional difference gel electrophoresis, proteins are labeled with fluorescent dyes before electrophoresis for more accurate quantitative expression analysis. We identified 11 protein spots that distinguished AFP-producing cell lines from nonproducing cell lines by multivariate studies. The spots showed consistent alterations in amount in AFP-producing cell lines (6 up-regulated and 5 down-regulated). An additional 5 liver cancer cell lines (KIM-1, KYN-2, KYN-3, PH5-CH, PH5-T) also were correctly grouped with respect to their AFP production on the basis of the intensity of the 11 protein spots. The proteins corresponding to the 11 selected spots were identified by mass spectrometry and were categorized into 4 groups based on their known role in apoptosis, glucose metabolism, cytoskeletal organization, or translation. In conclusion, we found a novel association of AFP with other proteins. Their interaction should provide insight into the biology of AFP-producing hepatocellular carcinoma cells.

Cell Line, Tumor↗

Nemo-like kinase suppresses a wide range of transcription factors, including nuclear factor-kappaB.

Nemo-like kinase (NLK) is a serine/threonine kinase that suppresses the transcription activity of the beta-catenin-T-cell factor (TCF) complex through phosphorylation of TCF. Our previous study showed that NLK overexpression induces apoptosis in DLD-1 human colon cancer cells and that apoptosis induction presumably requires a mechanism other than the suppression of beta-catenin-TCF complex. Luciferase reporter gene assay with pNF-kappaB-Luc revealed that NLK could suppress transcription activity of NF-kappaB in a kinase-dependent manner. However, it appeared that transcription co-activators of NF-kappaB, such as CREB binding protein (CBP)/p300, were likely to be the direct targets of NLK, rather than NF-kappaB itself. Luciferase reporter gene analysis of GAL4-CBP fusion proteins revealed that the C-terminal region of CBP was critical for transcription suppression by NLK. In vitro kinase assay showed that NLK could phosphorylate the C-terminal domain of CBP. However, HAT activity was not suppressed by the induction of wild-type NLK in DLD-1 cells. Furthermore, we observed that NLK suppressed the transcription activity of AP-1, Smad, and p53, all of which also utilize CBP as a co-activator. The extent of suppression by NLK was similar among the transcription factors tested (50-60% reduction). Our results suggest that NLK may suppress a wide range of gene expression, possibly through CBP.

CREB-Binding Protein↗

Surgical approach to tumor recurrence and metastatic lesions of the liver in a patient with malignant endocrine tumors of the pancreas: case report.

We describe herein a 72-year-old woman with tumor recurrence in the residual pancreas and metastasis to the liver following a pylorus-preserving pancreatoduodenectomy for multiple endocrine tumors in the head of the pancreas. Abdominal ultrasonography performed 7 years after the initial surgery detected new lesions in the residual pancreas and liver. After recurrence of endocrine tumors of the pancreas and metastasis to the liver were diagnosed, the lesions were successfully resected by total pancreatectomy with distal gastrectomy and both lateral segmentectomy and partial resection of segment 8. Genetic analysis using a blood specimen showed that this patient carried the multiple endocrine neoplasia type 1 (MEN1) gene mutation. One year after the second resection, the patient remains in good health using insulin and has not shown any sign of recurrence. This case report describes successful surgical resection for recurrence and metastasis of malignant endocrine tumors in a patient with the MEN1 gene mutation.

Aged↗