Genetic and epigenetic analysis of the <i>EPHB2</i> gene in gastric cancers

SONG, JAE HWI,KIM, CHANG JAE,CHO, YONG GU,KWAK, HYUN JUNG,NAM, SUK WOO,YOO, NAM JIN,LEE, JUNG YOUNG,PARK, WON SANG Wiley-Blackwell Munksgaard 2007 APMIS Vol. No.

<P>EPHB2 is a member of the Eph receptor tyrosine kinase family and a direct transcriptional target of &bgr;-catenin/TCF. EPHB2 plays an important role in maintaining the correct positioning of the proliferative compartment in the crypt-villous axis. A loss of EPHB2 expression has been observed in human tumors, particularly in colonic adenomas and carcinomas. A search was made for mutations at the A9 tract in exon 17, an allelic loss at the <I>EPHB2</I> gene locus, and promoter hypermethylation of the <I>EPHB2</I> gene in 81 sporadic gastric cancers in order to determine if genetic or epigenetic alterations of the <I>EPHB2</I> gene are involved in the development and/or progression of gastric cancer. Unexpectedly, no frameshift mutation was found and there was a low frequency (20.8%) of allelic loss. In addition, promoter hypermethylation was detected in only one gastric cancer tissue sample. Therefore, genetic or epigenetic alterations of the <I>EPHB2</I> gene might be an uncommon event in the development or progression of gastric cancers.</P>

Time-resolved X-ray PIV technique for diagnosing opaque biofluid flow with insufficient X-ray fluxes.

Jung, Sung Yong,Park, Han Wook,Kim, Bo Heum,Lee, Sang Joon Wiley-Blackwell Munksgaard 2013 Journal of synchrotron radiation Vol.20 No.3

<P>X-ray imaging is used to visualize the biofluid flow phenomena in a nondestructive manner. A technique currently used for quantitative visualization is X-ray particle image velocimetry (PIV). Although this technique provides a high spatial resolution (less than 10 ?m), significant hemodynamic parameters are difficult to obtain under actual physiological conditions because of the limited temporal resolution of the technique, which in turn is due to the relatively long exposure time (~10 ms) involved in X-ray imaging. This study combines an image intensifier with a high-speed camera to reduce exposure time, thereby improving temporal resolution. The image intensifier amplifies light flux by emitting secondary electrons in the micro-channel plate. The increased incident light flux greatly reduces the exposure time (below 200 ?s). The proposed X-ray PIV system was applied to high-speed blood flows in a tube, and the velocity field information was successfully obtained. The time-resolved X-ray PIV system can be employed to investigate blood flows at beamlines with insufficient X-ray fluxes under specific physiological conditions. This method facilitates understanding of the basic hemodynamic characteristics and pathological mechanism of cardiovascular diseases.</P>

Quantitative visualization of a gas diffusion layer in?a polymer electrolyte fuel cell using synchrotron X-ray imaging techniques.

Kim, Seung Gon,Lee, Sang Joon Wiley-Blackwell Munksgaard 2013 Journal of synchrotron radiation Vol.20 No.2

<P>A gas diffusion layer (GDL) in a polymer electrolyte fuel cell (PEFC) is quantitatively visualized using synchrotron X-ray micro-computed tomography. For three-dimensional reconstruction, an adaptive threshold method is used. This method is compared with the conventional method, i.e. Otsu's method. Additionally, the spatial and temporal variations of the porosity distribution of the GDL under freeze-and-thaw cycles are investigated experimentally. The freeze-and-thaw cycles are established simply using a CRYO system and light source illumination, respectively. Structural defects are found to largely affect the porosity of the GDL. In addition, a cyclic porosity variation is observed in the GDL under freeze-and-thaw cycles. The heterogeneous porosity is irreversibly decreased with the progress of repetitive cycles.</P>

<i>Pin1</i> gene mutation is a rare event in gastric cancer

KIM, CHANG JAE,SONG, JAE HWI,CHO, YONG GU,CHAE, HIUN SUK,NAM, SUK WOO,YOO, NAM JIN,LEE, JUNG YOUNG,PARK, WON SANG Wiley-Blackwell Munksgaard 2006 APMIS Vol. No.

<P>The peptidyl-prolyl isomerase Pin1 is strikingly overexpressed in human cancers and is a novel regulator of &bgr;-catenin. To determine whether somatic mutation of the <I>Pin1</I> gene is involved in the development and/or progression of gastric cancer, we searched for mutations of the <I>Pin1</I> gene in 95 gastric cancer specimens. The effect of <I>Pin1</I> on &bgr;-catenin expression was further examined in wild- and mutant-type <I>Pin1</I>-transfected HEK 293T cells. We found only one missense mutation that led to the substitution of alanine by aspartic acid at codon 118 of the <I>Pin1</I> gene. On transfection study, the mutant <I>Pin1</I> showed an increased expression of &bgr;-catenin. However, the mutation had no effect on expression of the Pin1 protein in the case with <I>Pin1</I> mutation. These results suggest that Pin1 may not play a role in the development or progression of gastric cancer.</P>

Immunohistochemical and mutational analysis of FLASH in gastric carcinomas.

Jeong, Eun Goo,Lee, Sung Hak,Lee, Hae Woo,Soung, Young Hwa,Yoo, Nam Jin,Lee, Sug Hyung Wiley-Blackwell Munksgaard 2007 APMIS Vol. No.

<P>FLASH was initially identified as a pro-apoptotic protein that transmits an apoptosis signal during death receptor-induced apoptosis. Additionally, diverse biologic roles of FLASH, including TNF-induced NF-kappaB activation, cell-cycle progression and cell division, have been identified. Although such functions are important in cancer pathogenesis, little is known about the alterations of FLASH gene and FLASH protein expression in human cancers. In this study, we analyzed the expression of FLASH protein in 60 gastric adenocarcinomas by immunohistochemistry. We furthermore analyzed mutation of FLASH in exon 8, where two polyadenine tracts ((A)8 and (A)9) are present, by single-strand conformation polymorphism (SSCP) assay in 184 gastric adenocarcinomas. By immunohistochemistry, FLASH protein expression in cancer cells was detected positively in 42 gastric carcinoma tissues (70%), whereas its expression in epithelial cells of normal gastric mucosa was shown as no or very weak intensity. Mutational analysis detected one FLASH mutation in the gastric carcinomas (0.5%). The increased expression of FLASH in the malignant gastric epithelial cells compared to the normal mucosal epithelial cells suggests that FLASH expression may play a role in gastric tumorigenesis. Also, the data suggest that somatic mutation of FLASH is a rare event in gastric carcinomas.</P>

Expression of phosphorylated caspase-9 in gastric carcinomas

YOO, NAM JIN,LEE, SUNG HAK,JEONG, EUN GOO,LEE, SUG HYUNG Wiley-Blackwell Munksgaard 2007 APMIS Vol. No.

<P>Alterations of caspases, the main executioners of apoptosis, have been described in human cancers. Caspase-9 plays a crucial role in the initiation phase of the intrinsic apoptosis pathway. Caspase-9 is phosphorylated at Thr125 through the mitogen-activated protein kinase (MAPK) pathway, and this phosphorylation is associated with inhibition of caspase-9 activation. The aim of this study was to explore whether phosphorylated caspase-9 (p-caspase-9) expression could be a characteristic of gastric carcinomas. We analyzed expression of p-caspase-9 protein in 60 gastric adenocarcinomas by immunohistochemistry using a tissue microarray approach. p-caspase-9 was detected in 33 of the 60 carcinomas (55%). Both early and advanced gastric carcinomas expressed p-caspase-9. There was no significant association of p-caspase-9 expression with clinocopathological characteristics, including invasion, metastasis and stage. In contrast to gastric cancer cells, epithelial cells in normal gastric mucosa showed no or only weak expression of p-caspase-9. Taken together, these results indicate that caspase-9 is frequently phosphorylated in gastric carcinomas, and that the phosphorylation of caspase-9 might be an inhibitory mechanism of caspase-9-mediated apoptosis in gastric carcinomas. Increased expression of p-caspase-9 in malignant gastric epithelial cells compared to normal mucosal epithelial cells suggests that p-caspase-9 expression might play a role in gastric carcinoma development.</P>

Somatic mutations of <i>BECN1</i>, an autophagy-related gene, in human cancers

LEE, JONG WOO,JEONG, EUN GOO,LEE, SUNG HAK,YOO, NAM JIN,LEE, SUG HYUNG Wiley-Blackwell Munksgaard 2007 APMIS Vol. No.

<P>Evasion of programmed cell death (PCD) is one of the hallmarks of human cancers. It is well known that not only apoptosis, but also autophagy, acts as an action mechanism of PCD. BECN1 protein is a key regulator of autophagic PCD. The <I>BECN1</I> gene that encodes BECN1 protein acts as a haploinsufficient tumor-suppressor gene. However, to date, data on <I>BECN1</I> mutation in human cancer tissues are lacking. To explore the possibility that somatic mutation of the <I>BECN1</I> gene might contribute to the development of human cancers, we analyzed the entire coding region and all splice sites of the human <I>BECN1</I> gene for detection of somatic mutations in 180 gastric carcinomas, 94 breast carcinomas, 50 acute leukemias, 50 colorectal carcinomas, 50 hepatocellular carcinomas, and 124 non-small cell lung cancers by single-strand conformation polymorphism (SSCP) and DNA sequencing. Overall, we detected 11 somatic mutations of the <I>BECN1</I> gene, including 3 missense mutations (N8K, P350R and R389C) in coding sequences and 8 mutations in introns. The mutations were observed in five gastric, three colorectal, one lung and one breast carcinoma (s). We expressed the three mutations (N8K, P350R and R389C) in HT1080 cells, and found that two (P350R and R389C) of them showed only slightly decreased cell death activities compared to the wild-type BECN1. This is the first report on <I>BECN1 </I>gene mutations in human cancer tissues, and the data suggest that point mutations are a rare event in common human cancers and probably do not play a major role in cancer pathogenesis.</P>

Deletion mutation of BRAF in a serrated adenoma from a patient with familial adenomatous polyposis

LEE, EUI JIN,PARK, CHEOL KEUN,KIM, JONG-WON,CHANG, DONG KYUNG,KIM, KYOUNG-MEE Wiley-Blackwell Munksgaard 2007 APMIS Vol. No.

<P>BRAF gene mutations in the colorectum have been associated with serrated adenomas and less frequently with hyperplastic polyps, villous adenomas, tubular adenomas, and carcinomas. Most BRAF mutations in the colon have been reported as a V600E substitution. We report a case with a very rare deletion mutation of BRAF (c.1799-1801delTGA, p.Val600_Lys601delinsGlu) in a serrated adenoma; the patient has familial adenomatous polyposis with a germline mutation of the APC gene (c.3578delA, p.Gln1193ArgfsX1264). Genetic studies on fundic gland polyps and tubular adenomas from the same patient failed to demonstrate BRAF mutation. This case is the first reported with a deletion mutation of BRAF found in the colon.</P>

Detection of circulating tumor cells via an X-ray imaging technique.

Jung, Sung Yong,Ahn, Sungsook,Seo, Eunseok,Lee, Sang Joon Wiley-Blackwell Munksgaard 2013 Journal of synchrotron radiation Vol.20 No.2

<P>Detailed information on the location and the size of tumor cells circulating through lymphatic and blood vessels is useful to cancer diagnosis. Metastasis of cancers to other non-adjacent organs is reported to cause 90% of deaths not from the primary tumors. Therefore, effective detection of circulating tumors cells (CTCs) related to metastasis is emphasized in cancer treatments. With the use of synchrotron X-ray micro-imaging techniques, high-resolution images of individual flowing tumor cells were obtained. Positively charged gold nanoparticles (AuNPs) which were inappropriate for incorporation into human red blood cells were selectively incorporated into tumor cells to enhance the image contrast. This approach enables images of individual cancer cells and temporal movements of CTCs to be captured by the high X-ray absorption efficiency of selectively incorporated AuNPs. This new technology for in vivo imaging of CTCs would contribute to improve cancer diagnosis and cancer therapy prognosis.</P>

Altered expression of CDX2 in colorectal cancers

CHOI, BYUNG JUN,KIM, CHANG JAE,CHO, YONG GU,SONG, JAE HWI,KIM, SU YOUNG,NAM, SUK WOO,LEE, SUG HYUNG,YOO, NAM JIN,LEE, JUNG YOUNG,PARK, WON SANG Wiley-Blackwell Munksgaard 2006 APMIS Vol.114 No.1

<P>CDX2 is a caudal-related homeobox transcription factor whose expression in the adult is normally restricted to the intestinal epithelium; it is implicated in the development and maintenance of the intestinal mucosa. The specific aim of this study was to elucidate the potential etiological role of CDX2 protein in colorectal carcinogenesis. We have analyzed the expression pattern of CDX2 protein in relation to the phenotype of 123 sporadic colorectal cancers by immunohistochemistry using tissue microarray. Strong CDX2 immunostaining was seen in the nuclei of corresponding normal intestinal epithelium. Interestingly, loss of CDX2 immunostaining was observed in 29 (23.6%) of 123 colorectal adenocarcinomas and its expression was correlated with the differentiation grade of the carcinoma (Chi-Square test, p<0.01). Clinically, CDX2 protein was immunopositive in 11 (91.7%) of 12 cases corresponding to stage A, 40 (85.1%) of 47 corresponding to stage B, 39 (69.6%) of 56 corresponding to stage C, and 4 (50.0%) of 8 corresponding to stage D. Statistically, CDX2 protein expression was related to tumor stage (Bartholomew test, p<0.05) and lymph node metastasis (Chi-Square test, p<0.05). These results indicate that loss of expression of CDX2 protein may play an important role in the tumorigenesis of colorectal cancers and that CDX2 expression represents a highly significant marker, which is able to identify a subset of patients at high risk.</P>