Immunohistochemical demonstration of alteration of β-catenin during tumor metastasis by different mechanisms according to histology in lung cancer

XU, XIANHUA,KIM, JI EUN,SUN, PING-LI,YOO, SEOL BONG,KIM, HYOJIN,JIN, YAN,CHUNG, JIN-HAENG D.A. Spandidos 2015 Experimental and therapeutic medicine Vol.9 No.2

<P>The protein β-catenin exhibits a dual function in cells, by acting as a major structural component of cell-cell adherens junctions and as a central signaling molecule in the Wnt signaling pathway. However, how the regulation of β-catenin expression during tumor metastasis in non-small cell lung cancer (NSCLC) varies according to histological type remains unclear. To investigate the regulatory mechanism of β-catenin on tumor metastasis, the present study compared the expression of Wnt1, β-catenin and E-cadherin in 41 primary NSCLC tumors and their corresponding metastatic lesions by immunohistochemistry. Altered expression of β-catenin was more frequent in the metastatic tumors (34/41, 82.9%) than in the corresponding primary tumors (24/41, 58.5%; P<0.05). There were 12 cases [nine of adenocarcinoma (ADC) and three of squamous cell carcinoma (SqCC)] that revealed discordant β-catenin expression between the primary tumors and the corresponding metastatic lesions. Of these, 11 cases (11/12, 91.7%; nine ADCs and two SqCCs) demonstrated acquired β-catenin alterations in the metastatic lesions. Subgroup analysis of these nine ADCs revealed that six cases (6/9, 66.7%) were accompanied by E-cadherin loss but no Wnt1 overexpression. Subgroup analysis of the three SqCCs revealed discordant β-catenin expression. Two cases (2/3, 66.7%) demonstrated acquired β-catenin expression during metastatic progression with Wnt1 overexpression but no change in E-cadherin expression. One case of SqCC revealed normal β-catenin expression in the metastasis although the expression was aberrant in the primary tumor. The results of the present study revealed that the changes in β-catenin expression occurred during tumor metastasis by different mechanisms, depending on histological type. The alterations in β-catenin expression may be regulated by a cadherin-catenin system in ADCs with reduced membranous expression of E-cadherin, but mediated by Wnt1 overexpression in SqCCs with cytoplasmic or nuclear transition types.</P>

High Incidence of EGFR Mutations in Korean Men Smokers with No Intratumoral Heterogeneity of Lung Adenocarcinomas: Correlation with Histologic Subtypes, EGFR/TTF-1 Expressions, and Clinical Features

Sun, Ping-Li,Seol, Hyesil,Lee, Hyun Ju,Yoo, Seol Bong,Kim, Hyojin,Xu, Xianhua,Jheon, Sanghoon,Lee, Choon-Taek,Lee, Jong-Suk,Chung, Jin-Haeng Elsevier 2012 Journal of thoracic oncology Vol.7 No.2

<P>Epidermal growth factor receptor (EGFR) mutation has been known to be associated with adenocarcinoma with bronchioloalveolar carcinoma (BAC; lepidic) feature. This study was aimed to characterize the frequency of EGFR mutations and their association with histologic subtypes in Korean nonsmall cell lung cancer (NSCLC) patients.</P>

동충하초 Paecilomyces tenuipes C240의 균사체 배양에 의한 세포외 다당체 생산의 동력학적 연구

윤종원,Chung Ping Xu 한국생명과학회 2005 생명과학회지 Vol.15 No.1

The unstructured model was tested to describe mycelial growth, exopolysaccharide formation, and substrate consumption in submerged mycelial culture of Paeciliomyces tenuipes C240. The Logistic equation for mycelial growth, the Luedeking-Piret equation for exopolysaccharide formation, and Luedeking- Piret-like equations for glucose consumptions were successfully incorporated into the model. The value of the key kinetic constants were: maximum specific growth rate (μm), 0.7281 h-1; growth- associated constant for exopolysaccharide production (α), 0.1743 g(g cells)-1; non-growth associated constant for exopolysaccharide production (β), 0.0019 g(g cells)-1; maintenance coefficient (ms), 0.0572 g (g cells)-1. When compared with batch experimental data, the model successfully provided a reasonable description for each parameter during the entire growth phase. The model showed that the production of exopolysaccharide in P. tenuipes C240 was growth-associated. The model tested in the present study can be applied to the design, scale-up, and control of fermentation process for other kinds of basidiomycetes or ascomycetes. 동충하초 Paecilomyces tenuipes C240의 균사체 배양과정에서 균사체 성장, 세포외 다당체 생산, 기질감소 속도를 표현할 수 있는 동력학적 모델을 제시하였다. 균사체 성장은 Logistic 식을, 세포외 다당체 생산은 Luedeking- Piret 식을, 기질소모는 Luedeking-Piret 유사식을 각각 적용함으로써, 전체 균사체 배양과정을 예측할 수 있었다. 모델식에서 사용된 주요 kinetic constant들은 다음과 같다: 균사체의 최대 비성장속도(μm), 0.7281 h-1; 다당체 생산에서의 growth-associated constant (α), 0.1743 g (g cells)-1; non-growth-associated constant (β), 0.0019 g (g cells)-1; maintenance coefficient (ms), 0.0572 g (g cells)-1. 5L 발효조에서 얻은 균사체 성장, 세포외 다당체 생산, 기질감소 속도자료들을 모델에서 예측한 결과와 비교한 결과 서로 잘 일치하는 것으로 보아, 본 연구에서 제안된 모델식은 이 동충하초 균사체 배양공정의 scale-up 등의 프로세스 설계에 응용가능 할 것이며, 다른 종류의 동충하초 균사체 배양공정에도 적용가능 할 것으로 판단된다.

Comparison of Direct Sequencing, PNA Clamping-Real Time Polymerase Chain Reaction, and Pyrosequencing Methods for the Detection of <i>EGFR</i> Mutations in Non-small Cell Lung Carcinoma and the Correlation with Clinical Responses to EGFR Tyrosine Kinase

Lee, Hyun Ju,Xu, Xianhua,Kim, Hyojin,Jin, Yan,Sun, Pingli,Kim, Ji Eun,Chung, Jin-Haeng The Korean Society of Pathologists and The Korean 2013 KOREAN JOURNAL OF PATHOLOGY - Vol.47 No.1

<P><B>Background</B></P><P>The aims of this study were to evaluate the abilities of direct sequencing (DS), peptide nucleic acid (PNA) clamping, and pyrosequencing methods to detect epidermal growth factor receptor (<I>EGFR</I>) mutations in formalin-fixed paraffin-embedded (FFPE) non-small cell lung carcinoma (NSCLC) samples and to correlate <I>EGFR</I> mutational status as determined by each method with the clinical response to <I>EGFR</I> tyrosine kinase inhibitors (TKIs).</P><P><B>Methods</B></P><P>Sixty-one NSCLC patients treated with EGFR TKIs were identified to investigate somatic mutations in the <I>EGFR</I> gene (exons 18-21).</P><P><B>Results</B></P><P>Mutations in the <I>EGFR</I> gene were detected in 38 of the 61 patients (62%) by DS, 35 (57%) by PNA clamping and 37 (61%) by pyrosequencing. A total of 44 mutations (72%) were found by at least one of the three methods, and the concordances among the results were relatively high (82-85%; kappa coefficient, 0.713 to 0.736). There were 15 discordant cases (25%) among the three different methods.</P><P><B>Conclusions</B></P><P>All three <I>EGFR</I> mutation tests had good concordance rates (over 82%) for FFPE samples. These results suggest that if the DNA quality and enrichment of tumor cells are assured, then DS, PNA clamping, and pyrosequencing are appropriate methods for the detection of <I>EGFR</I> mutations.</P>

The Role of Turmerones on Curcumin Transportation and P-Glycoprotein Activities in Intestinal Caco-2 Cells

Grace G.L. Yue,Sau-Wan Cheng,Hua Yu,Zi-Sheng Xu,Julia K.M. Lee,Po-Ming Hon,Mavis Y.H. Lee,Edward J. Kennelly,Gary Deng,Simon K. Yeung,Barrie R. Cassileth,Kwok-Pui Fung,Ping-Chung Leung,Clara B.S. Lau 한국식품영양과학회 2012 Journal of medicinal food Vol.15 No.3

The rhizome of Curcuma longa (turmeric) is often used in Asia as a spice and as a medicine. Its most wellstudied component, curcumin, has been shown to exhibit poor bioavailability in animal studies and clinical trials. We hypothesized that the presence of lipophilic components (e.g., turmerones) in turmeric extract would affect the absorption of curcumin. The effects of turmerones on curcumin transport were evaluated in human intestinal epithelial Caco-2 cells. The roles of turmerones on P-glycoprotein (P-gp) activities and mRNA expression were also evaluated. Results showed that in the presence of a- and aromatic turmerones, the amount of curcumin transported into the Caco-2 cells in 2 hours was significantly increased. a-Turmerone and verapamil (a P-gp inhibitor) significantly inhibited the efflux of rhodamine-123 and digoxin (i.e.,inhibited the activity of P-gp). It is interesting that aromatic turmerone significantly increased the rhodamine-123 efflux and Pgp (MDR1 gene) mRNA expression levels. The effects of a- and aromatic turmerones on curcumin transport as well as P-gp activities were shown here for the first time. The presence of turmerones did affect the absorption of curcumin in vitro. These findings suggest the potential use of turmeric extract (including curcumin and turmerones), rather than curcumin alone, for treating diseases.