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        Expression of Ezrin and Metastatic Tumor Antigen in Osteosarcomas of the Jaw

        Park, Hye-Rim,Cabrini, Romulo Luis,Araujo, Eduardo Santini,Paparella, Maria Luisa,Brandizzi, Daniel,Park, Yong-Koo SAGE Publications 2009 TUMORI Vol.95 No.1

        <P>AIMS AND BACKGROUND: Ezrin is a membrane-cytoskeleton linker protein involved in regulation of the growth and metastatic behavior of cancer cells. Metastatic tumor antigen (MTA) is a potential metastasis-associated protein. The objective of this study was to evaluate the expression of ezrin and MTA and their correlation with clinicopathological features in osteosarcomas of the jaw. METHODS: We analyzed ezrin and MTA protein levels by immunohistochemistry in 31 osteosarcomas of the jaw. RESULTS: The mean age at diagnosis was 39 years and half of the patients were male. The mandible (n = 19) was more frequently involved than the maxilla (n = 12). The predominant histological type was chondroblastic (58.1%) and 24 patients (77.4%) were classified as having a high grade of malignancy. Immunoreactivity for ezrin was identified in 6 of 31 cases (19.4%), while 77.4% displayed expression of MTA. All ezrin-positive patients had high-grade tumors. The high-grade tumors (n = 24) had a higher rate of MTA expression (42.9% vs 87.5%). Expression of ezrin and MTA was not significantly different according to age, sex, tumor site, histological type, and tumor ploidy. Follow-up information was available for 13 patients, with a mean follow-up time of 26.7 months (range, 6-48 months). At the time of last follow-up, 5 (38.5%) patients had died of disease and 8 patients (61.5%) were alive with no evidence of disease. Expression of ezrin and MTA was not significantly different according to the follow-up data. CONCLUSIONS: In our study, high-grade tumors had a higher rate of ezrin and MTA expression. This expression pattern indicates that ezrin and MTA positivity can be additional prognostic markers in osteosarcoma of the jaw.</P>

      • KCI등재

        The Global Histone Modification Patterns of Osteosarcoma

        도성임,임성직,김윤화,Liliana G. Olvi,Eduardo Santini-Araujo,박용구 대한병리학회 2011 Journal of Pathology and Translational Medicine Vol.45 No.2

        Background: Epigenetic alteration may affect a patient’s prognosis by altering the development and progression of the tumor. Some recent reports have identified a correlation between histone modification and patient outcome. However, no studies have been conducted on global histone modification in osteosarcomas. Methods: We investigated histone modification in 54 cases of osteosarcoma by performing immunohistochemical staining. The immunohistochemical expres­sion of four histone modification markers, acetylated H4 lysine 12 (H4K12Ac), acetylated H3 ly­sine 18, trimethylated H3 lysine 27, and dimethylated H3 lysine 4 were evaluated. Results: High H4K12Ac expression was correlated with patient age (p=0.011). However, the other histone mod­ification markers showed no correlation with any of the clinicopathological data such as survival, tumor grade, tumor site, metastasis, age, or gender. Conclusions: Our study showed that all four histone modification markers are expressed in osteosarcoma (median expression rate, 40 to 60%). However, we did not find a correlation with the clinicopathological factors except for age. Further study to evaluate the reason for the association between H4K12Ac and patient age is needed.

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        IDH Mutation Analysis in Ewing Sarcoma Family Tumors

        나기용,박용구,노병주,성지윤,김윤화,Eduardo Santini Araujo 대한병리학회 2015 Journal of Pathology and Translational Medicine Vol.49 No.3

        Background: Isocitrate dehydrogenase (IDH) catalyzes the oxidative decarboxylation of isocitrate to yield α-ketoglutarate (α-KG) with production of reduced nicotinamide adenine dinucleotide (NADH). Dysfunctional IDH leads to reduced production of α-KG and NADH and increased production of 2-hydroxyglutarate, an oncometabolite. This results in increased oxidative damage and stabilization of hypoxia-inducible factor α, causing cells to be prone to tumorigenesis. Methods: This study investigated IDH mutations in 61 Ewing sarcoma family tumors (ESFTs), using a pentose nucleic acid clamping method and direct sequencing. Results: We identified four cases of ESFTs harboring IDH mutations. The number of IDH1 and IDH2 mutations was equal and the subtype of IDH mutations was variable. Clinicopathologic analysis according to IDH mutation status did not reveal significant results. Conclusions: This study is the first to report IDH mutations in ESFTs. The results indicate that ESFTs can harbor IDH mutations in previously known hot-spot regions, although their incidence is rare. Further validation with a larger case-based study would establish more reliable and significant data on prevalence rate and the biological significance of IDH mutations in ESFTs.

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        14-bp Insertion/Deletion Polymorphism of the HLA-G Gene in Osteosarcoma Patients

        문아림,김수강,정주호,나기용,Liliana G. Olvi,Eduardo Santini-Araujo,김윤화,박용구 대한병리학회 2011 Journal of Pathology and Translational Medicine Vol.45 No.5

        Background: The major histocompatibility complex class I, G (human leukocyte antigen-G [HLA-G]) gene plays a vital role in the suppression of immune responses. Recently, a number of studies have reported an association between HLA-G and diseases (pregnancy complications, organ transplantation, and tumors). Some of the studies have revealed that the 14-bp insertion/deletion polymorphism might be associated with various diseases. The aim of the present study was to explore a possible influence of the 14-bp insertion/deletion polymorphism on osteosarcoma. Methods: Genomic DNA was extracted from 75 formalin-fixed, paraffin-embedded tumor tissues derived from patients with conventional osteosarcoma (OSA) and 183 peripheral blood samples of healthy controls. Fifty-eight cases were South Korean patients with OSA and 17 cases were Argentine patients with OSA. The HLA-G 14-bp insertion/deletion polymorphism at exon 8 of the HLA-G locus was analyzed by polymerase chain reaction. Results: There was a significantly different distribution profile for the 14-bp genotypes between the Korean OSA and Korean control groups. Specifically, there were more heterozygote 210 bp/224 bp genotypes in the Korean OSA group when compared to the Korean control group (62.1% vs 40.4%, p=0.002). Conclusions: The results suggest that HLA-G heterozygote patients may be more susceptible to OSA in the Korean population.

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