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Jeung, Hei-Cheul,Rha, Sun Young,Shin, Sang Joon,Lim, Seung Joon,Roh, Jae Kyung,Noh, Sung Hoon,Chung, Hyun Cheol Lippincott Williams Wilkins, Inc. 2011 Anti-cancer drugs Vol.22 No.8
Determination of significant associations between gene expression and predefined endpoints might improve treatment tailoring for advanced gastric cancer. We investigated the mRNA expression of 5-fluorouracil (5-FU) pathway genes in prechemotherapeutic tumor samples of primary gastric cancer to try to predict the treatment outcome of S-1 monotherapy. 5-FU pathway genes, dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyltransferase (OPRT), thymidylate synthase (TS), and thymidine phosphorylase (TP), were analyzed using quantitative real-time PCR of RNA extracted from archived formalin-fixed paraffin-embedded tissues. We selected the median value for each gene as a cutoff to separate patients into high and low gene expression groups. High OPRT gene expression was significantly associated with tumor response (P=0.014). In a combined analysis including OPRT, patients with high OPRT and TP showed a higher overall response rate than did the remaining patients (40 vs. 10%, respectively; P=0.002). For survival, patients with high OPRT and low TS levels showed prolonged survival in both progression-free survival (3.4 vs. 2.4 months, P=0.024) and overall survival (11.0 vs. 8.2 months, P=0.007). In a multivariate analysis, the combinations of OPRT and TP for response and OPRT and TS for both progression-free survival and overall survival were independent variables. To conclude, mRNA expression levels of molecular markers in formalin-fixed paraffin-embedded specimens of primary gastric tumors can be useful for identifying patients with advanced gastric cancer who would most likely benefit from S-1 treatment.
Jeung, Hei-Cheul,Rha, Sun Young,Shin, Sang Joon,Ahn, Joong Bae,Noh, Sung Hoon,Roh, Jae Kyung,Chung, Hyun Cheol Oxford University Press 2010 Japanese journal of clinical oncology Vol.40 No.1
<P><B>Objective</B></P><P>In this study, we compared the pharmacokinetic profiles of 5-fluorouracil (5-FU), tegafur, 5-chloro-2,4-dihydroxypyridine (CDHP) and potassium oxonate (Oxo) after administration of S-1 at 35 or 40 mg/m<SUP>2</SUP> bid for 28 consecutive days, in Cycles 1 and 3, in patients with advanced gastric cancer.</P><P><B>Methods</B></P><P>Three patients were enrolled for each dosage. S-1 dosage was assigned based on body surface area (BSA), which is different from the Japanese dosing system. The median daily dose per BSA was 76 mg/m<SUP>2</SUP>, ranging from 70 to 88 mg/m<SUP>2</SUP>.</P><P><B>Results</B></P><P>Plasma levels of 5-FU, tegafur, CDHP and Oxo at 4 h post-dose reached steady-state on day 8. The estimated steady-state level was dependent on S-1 dosage. There were no intercyclic differences of pre-dose and 4 h post-dose levels between Cycles 1 and 3, implying no cumulative effect of S-1 was shown probably due to 2-week drug-resting period. Pharmacokinetic profiles on day 28 were similar to previous Japanese report. <I>C</I><SUB>max</SUB> and AUC<SUB>0–48 h</SUB> values of each S-1 component increased depending on S-1 dosage. Pharmacokinetic parameters were not correlated with tumor response or toxicity.</P><P><B>Conclusions</B></P><P>We suggest that these pharmacokinetic profiles of Asian population could provide a basis for schedule optimization and for additional studies on interaction with other antitumor drugs.</P>
진행성 악성종양별 맞춤 항암요법의 최신 지견 ; 위암의 맞춤 항암 요법의 최신 지견
정희철 ( Hei Cheul Jeung ),라선영 ( Sun Young Rha ) 대한내과학회 2009 대한내과학회지 Vol.77 No.1
Even the overall incidence is decreasing and the proportion of early gastric cancer is increasing from the national mass screening program, still gastric cancer is the major issue in Korea. Multimodality approach and the development of novel therapeutic agents enabled us to improve the survival rate of gastric cancer. However, the proper treatment strategy for the subgroups of patients is necessary, which is now categorized based on the clinicopathologic parameters. We need more in-depth information regarding the molecular biology of gastric cancer, and the development of novel targeted biological agents and the biomarkers for the future. Currently, the recent chemotherapeutic agents showed the improved response in advanced gastric cancer. Hence, the basic concept of adjuvant chemotherapy, palliative chemotherapy, neoadjuvant treatment with or without incorporation of radiotherapy become settle down with more evidences from several phase III trials. Especially, after understanding the difference between Asia and Western countries including biology, ethnic difference, operation technology, and the treatment approaches, the qualified, well-designed multinational clinical trials are on-going. Based on the current results, here, I describe the current status of gastric cancer treatment strategy. (Korean J Med 77:1-8, 2009)
Jeung, Hei‐,Cheul,Rha, Sun Young,Im, Chong Kun,Shin, Sang Joon,Ahn, Joong Bae,Yang, Woo Ick,Roh, Jae Kyung,Noh, Sung Hoon,Chung, Hyun Cheol Wiley Subscription Services, Inc., A Wiley Company 2011 Cancer Vol.117 No.10
<P><B>Abstract</B></P><P><B>BACKGROUND:</B></P><P>The purpose of this study was to compare 2 weekly docetaxel‐based regimens as first‐line treatments for advanced gastric cancer and to investigate the expression of secreted protein acidic and rich in cysteine (SPARC) and its abilities to predict treatment‐related clinical outcomes.</P><P><B>METHODS:</B></P><P>Patients were randomly selected to receive 3 weekly cycles of docetaxel (35 mg/m<SUP>2</SUP> on days 1 and 8) plus S‐1 (35 mg/m<SUP>2</SUP> each twice daily on days 1‐14) (DS), or docetaxel plus cisplatin (35 mg/m<SUP>2</SUP> each on days 1 and 8) (DC). Endpoints included overall response rate (primary), survival, toxicity, and quality of life (secondary). SPARC expression in prechemotherapy specimens of primary gastric tumors was evaluated via immunohistochemical analysis.</P><P><B>RESULTS:</B></P><P>Eighty patients were enrolled in the study. Confirmed overall response rates were 46% (95% confidence interval, 30%‐62%) for DS and 24% (95% confidence interval, 11%‐38%) for DC via intent‐to‐treat analysis. Median progression‐free survival was 7.3 and 4.9 months and overall survival was 16.0 and 8.3 months for DS and DC, respectively. The most common grade ≥3 toxicity was neutropenia. Grade ≥3 mucositis (18%) and hand‐foot syndrome (8%) were the toxicities most associated with DS, whereas anorexia (20%) and lethargy (20%) were more common with DC. High SPARC expression was related to early progression (hazard ratio, 3.67; <I>P</I> = .042) and poor overall survival (hazard ratio, 2.01; <I>P</I> = .010) in docetaxel chemotherapy on multivariate analysis.</P><P><B>CONCLUSIONS:</B></P><P>The outcomes in this study favored DS over DC for further phase 3 study. The findings suggest that split‐dose weekly docetaxel alleviates hematological toxicity without compromising efficacy, and that SPARC expression may help individualize therapy in advanced gastric cancer. Cancer 2011. © 2010 American Cancer Society.</P>
Yang, Sanghwa,Jeung, Hei-Cheul,Jeong, Ha Jin,Choi, Yeon Ho,Kim, Ji Eun,Jung, Jae-Joon,Rha, Sun Young,Yang, Woo Ick,Chung, Hyun Cheol Elsevier 2007 Genomics Vol.89 No.4
<P><B>Abstract</B></P><P>To identify DNA copy number changes that had a direct influence on mRNA expression in gastric cancer, cDNA microarray-based comparative genomic hybridization (aCGH) and gene expression profiling were performed using 17?K cDNA microarrays. A set of 158 genes showing Pearson correlation coefficients over 0.6 between DNA copy number changes and mRNA expression level variations was selected. In an independent gene expression profiling of 60 tissue samples, the 158 genes were able to distinguish most of the normal and tumor tissues in an unsupervised hierarchical clustering, suggesting that the differential expression patterns displayed by this specific group of genes are most likely based on the gene copy number changes. Furthermore, 43 statistically significant (<I>P</I><0.01) genes were selected that correctly distinguished all of the tissue samples. The copy number changes detected by aCGH can be verified by fluorescence <I>in situ</I> hybridization and real-time polymerase chain reaction. The selected genes include those that were previously identified as being tumor suppressors or deleted in various tumors, including <I>GATA binding protein 4</I> (GATA4), <I>monoamine oxidase A</I> (MAOA), <I>cyclin C</I> (CCNC), and oncogenes including <I>malignant fibrous histiocytoma amplified sequence 1</I> (MFHAS1/MASL1), <I>high mobility group AT-hook 2</I> (HMGA2), <I>PPAR binding protein</I> (PPARBP), <I>growth factor receptor-bound protein 7</I> (GRB7), and <I>TBC1 (tre-2, BUB2, cdc16) domain family, member 1</I> (TBC1D1).</P>
The clinical significance of ascitic fluid CEA in advanced gastric cancer with ascites
Jung, Minkyu,Jeung, Hei-Cheul,Lee, Sung Sook,Park, Jun Yong,Hong, Soojung,Lee, Soo Hyeon,Noh, Sung Hoon,Chung, Hyun Cheol,Rha, Sun Young Springer-Verlag 2010 Journal of Cancer Research and Clinical Oncology Vol.136 No.4