1.Significant Gene Selection Using Integrated Microarray Data Set with Batch Effect.
Ki Yeol KIM ; Hyun Cheol CHUNG ; Hei Cheul JEUNG ; Ji Hye SHIN ; Tae Soo KIM ; Sun Young RHA
Genomics & Informatics 2006;4(3):110-117
In microarray technology, many diverse experimental features can cause biases including RNA sources, microarray production or different platforms, diverse sample processing and various experiment protocols. These systematic effects cause a substantial obstacle in the analysis of microarray data. When such data sets derived from different experimental processes were used, the analysis result was almost inconsistent and it is not reliable. Therefore, one of the most pressing challenges in the microarray field is how to combine data that comes from two different groups. As the novel trial to integrate two data sets with batch effect, we simply applied standardization to microarray data before the significant gene selection. In the gene selection step, we used new defined measure that considers the distance between a gene and an ideal gene as well as the between-slide and within-slide variations. Also we discussed the association of biological functions and different expression patterns in selected discriminative gene set. As a result, we could confirm that batch effect was minimized by standardization and the selected genes from the standardized data included various expression pattems and the significant biological functions.
Bias (Epidemiology)
;
Computational Biology
;
Dataset*
;
Genes, vif
;
RNA
2.Benefits of Recurrent Colonic Stent Insertion in a Patient with Advanced Gastric Cancer with Carcinomatosis Causing Colonic Obstruction.
Semi PARK ; Sang Joon SHIN ; Joong Bae AHN ; Hei Cheul JEUNG ; Sun Young RHA ; Sang Kil LEE ; Hyun Cheol CHUNG
Yonsei Medical Journal 2009;50(2):296-299
Malignant obstruction develops frequently in advanced gastric cancer. Although it is primarily the gastric outlet that is obstructed, there are occasional reports of colonic obstruction. Treating intestinal obstruction usually requires emergency surgery or stent insertion. There are several kinds of complications with stent insertion, such as bowel perforation, stent migration, bleeding, abdominal pain and reobstruction. Nevertheless, endoscopic stent insertion could be a better treatment than emergency surgery in cases of malignant bowel obstruction in cancer patients with poor performance status. We report a case of advanced gastric cancer with carcinomatosis in which a recurrent colonic stent was inserted at the same site because of cancer growth into the stent. The patient maintained a good condition for chemotherapy, thus improving their chances for survival.
Aged
;
Female
;
Humans
;
Intestinal Obstruction/etiology/radiography/*surgery
;
Neoplasm Recurrence, Local
;
Prosthesis Implantation/*methods
;
*Stents
;
Stomach Neoplasms
3.Synchronous elevation of soluble intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) correlates with gastric cancer progression.
Nae Choon YOO ; Hyun Cheol CHUNG ; Hei Cheol CHUNG ; Joon Oh PARK ; Sun Young RHA ; Joo Hang KIM ; Jae Kyung ROH ; Jin Sik MIN ; Byung Soo KIM ; Sung Hoon NOH
Yonsei Medical Journal 1998;39(1):27-36
Soluble forms of ICAM-1 (sICAM-1) and VCAM-1 (sVCAM-1) have been reported from the supernatant of cytokine-activated endothelial cells, cancer cells and from sera of cancer patients. We measured sICAM-1 and sVCAM-1 from the serum of 20 healthy volunteers and 142 gastric cancer patients by ELISA assay. Ninety-five patients were operable and 47 patients were in-operable at the time of this study. Particularly in the 28 operable patients, we sampled both portal and peripheral blood simultaneously and measured the levels of the soluble forms of cell adhesion molecules (sCAMs). The sCAMs level and sero-positivity rate increased with cancer progression in order of the healthy controls, operable patients, and inoperable patients. In in-operable cancer, the sICAM-1 level increased more with liver metastasis. sICAM-1 and sVCAM-1 did not correlate with each other in either portal or peripheral blood. A total of 58.3% of patients with liver metastasis and 22.9% of patients without liver metastasis showed synchronous expression of both sCAMs (p = 0.03). Synchronous sero-positivity of sCAMs and alpha FP was higher with liver metastasis (p = 0.01). The median overall survival duration which co-expressed both sCAMs was 9 months. This showed a significant difference compared with the sICAMs non-expressing group, where the median survival was not reached until 24 months follow-up (p = 0.002). The synchronous expression of sCAMs was an independent risk factor in gastric cancer patients. We raise the possibility that synchronous sICAM-1 and sVCAM-1 elevation may be a useful monitor to determine tumor burden in gastric cancer.
Adult
;
Aged
;
Female
;
Human
;
Intercellular Adhesion Molecule-1/blood*
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Liver Neoplasms/secondary
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Male
;
Middle Age
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Stomach Neoplasms/mortality
;
Stomach Neoplasms/blood*
;
Survival Rate
;
Vascular Cell Adhesion Molecule-1/blood*
4.A case of toxoplasmosis mimicking systemic recurrence in a patient treated with breast cancer.
Beom Kyung KIM ; Byoung Chul CHO ; Yong Won LEE ; Hyun Soo CHUNG ; Hei Cheul JEUNG ; Sun Yong RHA ; Hyun Cheol CHUNG
Korean Journal of Medicine 2006;71(1):108-113
Left cervical lymphadenopathy was found in a 48-year-old Korean female patient who had been treated for breast cancer 3 years ago. A presumative diagnosis was lymph nodal and lung metastasis of breast cancer during chest CT and neck CT. Core needle biopsy was undertaken. Pathological examination of lymph node revealed reactive hyperplasia consistent with toxoplasmosis, and toxoplasma Ig M antibody was also positive. Finally, she was diagnosed as toxoplasmosis, not metastasis of breast cancer. As she had no symptoms, no specific treatment was necessary. Follow up chest and neck CT scan after 5 months later showed resolved lung lesion, and size decrement of cervical lymph node. So, she has no evidence of recurrence and is now under clinical follow up. Recognition that toxoplasmosis can mimic metastasis is important in reaching the correct diagnosis and treatment.
Biopsy, Large-Core Needle
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Breast Neoplasms*
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Breast*
;
Diagnosis
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Female
;
Follow-Up Studies
;
Humans
;
Hyperplasia
;
Lung
;
Lymph Nodes
;
Lymphatic Diseases
;
Middle Aged
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Neck
;
Neoplasm Metastasis
;
Recurrence*
;
Thorax
;
Tomography, X-Ray Computed
;
Toxoplasma
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Toxoplasmosis*
5.A Locally Advanced Breast Cancer with Difficult Differential Diagnosis of Carcinosarcoma and Atypical Medullary Carcinoma, which had Poor Response to Adriamycin- and Taxane-based Neoadjuvant Chemotherapy: A Case Report.
Se Hyun KIM ; Hyun Cheol CHUNG ; Jaeheon JEONG ; Ji Hoon KIM ; Sun Young RHA ; Joong Bae AHN ; Nam Hoon CHO ; Hei Cheul JEUNG
Cancer Research and Treatment 2007;39(3):134-137
Atypical medullary carcinomas and carcinosarcoma have unique histopathological features. Here we present a case with a breast malignancy that had pathological characteristics of both. A 54-year old patient with a malignant breast mass received 6 cycles of adriamycin-based chemotherapy, followed by 3 cycles of paclitaxel monotherapy, and had a poor clinical response to treatment. A modified radical mastectomy was performed. The pathological diagnosis was complicated by an inability to distinguish between atypical medullary carcinoma and carcinosarcoma. The findings included a tumor that was well-circumscribed, high grade and a syncytial growth pattern as well as biphasic sarcomatous and carcinomatous characteristics. In conclusion, atypical medullary carcinoma and carcinosarcoma of the breast have entirely different prognoses and should be managed differently. Both should be treated by surgical resection, and additional therapy should be considered based on the cancer with the poorer prognosis.
Breast Neoplasms*
;
Breast*
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Carcinoma, Medullary*
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Carcinosarcoma*
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Diagnosis
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Diagnosis, Differential*
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Drug Therapy*
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Humans
;
Mastectomy, Modified Radical
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Middle Aged
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Paclitaxel
;
Prognosis
6.Leptomeningeal Carcinomatosis in Solid Tumors; Clinical Manifestation and Treatment.
Joon Oh PARK ; Hyun Joon SHIN ; Hyung Jong KIM ; Sang Wook LEE ; Hei Cheul JEUNG ; Seung Min KIM ; Nae Choon YOO ; Hyun Cheol CHUNG ; Joo Hang KIM ; Byung Soo KIM ; Jin Sik MIN ; Jae Kyung ROH
Journal of the Korean Cancer Association 2001;33(1):34-40
PURPOSE: Leptomeningeal carcinomatosis occurs in about 5% of patients with solid tumor and is being diagnosed with increasing frequency as patients live longer and as neuro-imaging studies improve. In general, the most commom cancers that involved the leptomeninges are breast cancer, lung cancer, and malignant melanoma. MATERIALS AND METHODS: We investigated 25 patients presented with multiple neurologic symptoms and signs who were diagnosed with leptomeningeal carcinomatosis at the Yonsei Cancer Center from January 1990 to December 1999. RESULTS: The primary disease of leptomeningeal carcinomatosis were stomach cancer (10 cases), breast cancer (7 cases), lung cancer (5 cases), unknown primary cancer (2 cases) and common bile duct cancer (1 case). All patients were presented with multiple neurologic symptoms and signs involving the central nervous system (CNS), cranial nerve or spinal nerves. Twenty-one of twenty- five patients were treated with intrathecal chemotherapy, radiotherapy, or combination therapy. Fourteen of them (66.7%) experienced improvement or stabilization of neurologic symptom and sign. The median survival was 122 days (10-2190). CONCLUSION: In conclusion, although early diagnosis and active treatment of leptomeningeal carcinomatosis may improve the quality of life in selected patients, the median survival was relatively short. Therefore, new diagnostic and therapeutic strategy for leptomeningeal carcinomatosis were needed.
Breast Neoplasms
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Central Nervous System
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Common Bile Duct
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Cranial Nerves
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Drug Therapy
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Early Diagnosis
;
Humans
;
Lung Neoplasms
;
Melanoma
;
Meningeal Carcinomatosis*
;
Neurologic Manifestations
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Quality of Life
;
Radiotherapy
;
Spinal Nerves
;
Stomach Neoplasms
7.S-1 Monotherapy as a Neoadjuvant Treatment for Locally Advanced Gastric Cancer.
Jong Yul JUNG ; Sun Young RHA ; Joong Bae AHN ; Woo Ick YANG ; Sung Hoon NOH ; Hyun Cheol CHUNG ; Hei Cheul JEUNG
The Korean Journal of Internal Medicine 2008;23(1):37-41
S-1, a novel oral fluoropyrimidine, is an effective therapeutic agent for gastric cancer. Herein, we report a case with locally advanced gastric cancer that achieved a curative resection after S-1 monotherapy as neoadjuvant treatment. A 68-year-old man was diagnosed with gastric cancer and massive lymphadenopathy involving the perigastric, celiac axis and splenic hilum. His clinical stage was cT3N2H0P0M0. Considering his relatively poor performance (ECOG 2, severe weight loss) and advanced age, we started the patient on S-1 monotherapy at a dose of 35 mg/m2 bid for 4 consecutive weeks followed by a 2-week rest. Follow-up study after 4 treatment cycles revealed disappearance of the lymphadenopathy of the perigastric and celiac axis with diminished extension of the stomach mass. The patient had a partial response (PR) with a 72% tumor reduction, according to the Response Evaluation Criteria in Solid Tumors (RECIST). His performance status was improved to an ECOG 1 and he gained 7 kg. A curative (R0) resection was achieved with a radical total gastrectomy and D2 dissection. The pathological stage was pT3N2M0, stage IIIB. In conclusion, S-1 neoadjuvant chemotherapy aided in the treatment of gastric cancer in this patient.
Adenocarcinoma/*drug therapy/pathology/surgery
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Aged
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Antimetabolites, Antineoplastic/administration & dosage/*therapeutic use
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Drug Combinations
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Gastrectomy
;
Humans
;
Male
;
*Neoadjuvant Therapy
;
Neoplasm Staging
;
Oxonic Acid/administration & dosage/*therapeutic use
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Stomach Neoplasms/*drug therapy/pathology/surgery
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Tegafur/administration & dosage/*therapeutic use
8.The UGT1A9*22 genotype identifies a high-risk group for irinotecan toxicity among gastric cancer patients
Choong-kun LEE ; Hong Jae CHON ; Woo Sun KWON ; Hyo-Jeong BAN ; Sang Cheol KIM ; Hyunwook KIM ; Hei-Cheul JEUNG ; Jimyung CHUNG ; Sun Young RHA
Genomics & Informatics 2022;20(3):e29-
Several studies have shown associations between irinotecan toxicity and UGT1A genetic variations in colorectal and lung cancer, but only limited data are available for gastric cancer patients. We evaluated the frequencies of UGT1A polymorphisms and their relationship with clinicopathologic parameters in 382 Korean gastric cancer patients. Polymorphisms of UGT1A1*6, UGT1A1*27, UGT1A1*28, UGT1A1*60, UGT1A7*2, UGT1A7*3, and UGT1A9*22 were genotyped by direct sequencing. In 98 patients treated with irinotecan-containing regimens, toxicity and response were compared according to the genotype. The UGT1A1*6 and UGT1A9*22 genotypes showed a higher prevalence in Korean gastric cancer patients, while the prevalence of the UG1A1*28 polymorphism was lower than in normal Koreans, as has been found in other studies of Asian populations. The incidence of severe diarrhea after irinotecan-containing treatment was more common in patients with the UGT1A1*6, UGT1A7*3, and UGT1A9*22 polymorphisms than in controls. The presence of the UGT1A1*6 allele also showed a significant association with grade III–IV neutropenia. Upon haplotype and diplotype analyses, almost every patient bearing the UGT1A1*6 or UGT1A7*3 variant also had the UGT1A9*22 polymorphism, and all severe manifestations of UGT1A polymorphism-associated toxicity were related to the UGT1A9*22 polymorphism. By genotyping UGT1A9*22 polymorphisms, we could identify high-risk gastric cancer patients receiving irinotecan-containing chemotherapy, who would experience severe toxicity. When treating high-risk patients with the UGT1A9*22 polymorphism, clinicians should closely monitor them for signs of severe toxicity such as intense diarrhea or neutropenia.
9.Clinical Significance of Urokinase - type Plasminogen Activator Receptor ( uPAR ) Expression in Breast Cancer Tissues.
Soo Jung GONG ; Sun Young RHA ; Hei Chul JUNG ; Joon Oh PARK ; Nae Choon YOO ; Jae Kyung ROH ; Woo Ick YANG ; Kyong Sik LEE ; Jin Sik MIN ; Byung Soo KIM ; Hyun Cheol CHUNG
Journal of the Korean Cancer Association 2000;32(1):53-59
PURPOSE: Cancer invasion is induced by several proteolytic enzyme systems associated with the destruction of basement membrane and extracellular matrix. Urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) have been reported as prognostic factors in breast cancer patients and plasminogen activation is regulated by various factor such as uPAR and growth factor. So we examined the tissue levels of urokinase-type plasminogen activator receptor (uPAR) in breast cancer patients. MATERIALS AND METHODS: Tissue uPAR levels were measured by ELISA assay in 268 breast cancer patients. RESULTS: The median and mean values of tissue uPAR level in breast cancer were 3.5 ng/mg and 4.8+-3.6 ng/mg cytosol protein, respectively. Tissue uPAR level was the highest in T1 stage, but there was no statistical significance between T stage (p >0.05). In nodal stage, there was also no difference in the value of uPAR according to progression. And the value of uPAR expression was not associated with estrogen and progesteron receptor status, number of involved node and percent of node involvement. In TNM stage, tissue uPAR levels were higher in patients with stage I-II than in patients with stage III-IV (p=0.027). In univariate analysis, nodal factor (p=0.0023) and TNM stage (p=0.0004) were significantly associated with overall survival. But, multivariate analysis showed that TNM stage was the only significant prognostic factor (p=0.0002). CONCLUSION: These results suggest that uPAR is mainly associated with initial tumor invasion and other factors might be involved in later stages of cancer progression.
Basement Membrane
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Breast Neoplasms*
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Breast*
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Cytosol
;
Enzyme-Linked Immunosorbent Assay
;
Estrogens
;
Extracellular Matrix
;
Humans
;
Multivariate Analysis
;
Plasminogen Activators*
;
Plasminogen*
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Urokinase-Type Plasminogen Activator*
10.Application of Gabexate Mesylate IC against MMP - 9 Using ex vivo Model in Gastric Cancer: Prognostic Factor and Selection Criteria for Anti - MMP Treatment.
Yong Wha MOON ; Hoon YANG ; Hei Chul JUNG ; Sun Young RHA ; Tae Soo KIM ; Nae Choon YOO ; Sung Hoon NOH ; Jae Kyung ROH ; Jin Sik MIN ; Byung Soo KIM ; Hyun Cheol CHUNG
Journal of the Korean Cancer Association 2000;32(1):7-18
PURPOSE: Among the many biological characteristics of cancer, matrix metalloproteinases(MMPs) are essential for tumor invasion and metastasis. The correction of the imbalance between MMPs and tissue inhibitors of matrix metalloproteinase (TIMP) has been suggested as a possible goal for the control of invasive phenotype of the cancer. To test the possible inhibition of MMP-9 in ex vivo model and the selection of the patients who are sensitive to MMP inhibitory (MMPI) treatment, we evaluated IC50 of the gabexate mesylate (Foy) against MMP-9 and compared them to the clinical parameters and patients survivals. MATERIALS AND METHODS: Thirty-four paired normal and gastric cancer tissues were tested for the IC50 of the gabexate mesylate. MMP-9 activity was measured by zymography. RESULTS: MMP-9 expression (percent of sample band density to control band) (p=0.04) and IC50 (p=0.02) of cancer tissues were significantly higher than those of normal tissues. Cancer tissue IC50 was higher than that of normal tissues in cases when the tumor mass diameter was longer than 5 cm (p=0.03) as well as in higher T-stage (p=0.04), lymph node metastasis (p=0.04) and in advanced stages (p=0.04). There was a tendency of increased IC50 of diffuse and mixed type than that of intestinal type (diffuse & mixed: 11.0+-20.8 mg/ml, intestinal: 2.7+-3.9 mg/ml; p 0.07), in spite of no difference in MMP-9 expression (diffuse & mixed: 40.3+49.2%, intestinal: 51.0+-58.0%). In early gastric cancer (EGC), there was no difference in IC50 between normal and cancer tissues whereas cancer tissue IC50 was higher than that of normal tissue in advanced gastric cancer (p 0.02). There was a tendency of increment of ICo in cancer tissues of advanced gastric cancer than that of EGC whereas no difference was found in MMP-9 expression between these types of cancers. Poor prognosis was found in high IC50 patients in curatively resected patients (p=0.04). In multivariate analysis, high IC50 was suggested as a possible independent prognostic factor. CONCLUSION: We could differentiate the high risk patients using IC50 of gabexate mesylate in ex vivo model. This model can be applied in detecting patients with poor prognosis and patients who can have a possible benefit with MMPI treatment.
Gabexate*
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Humans
;
Inhibitory Concentration 50
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Lymph Nodes
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Matrix Metalloproteinases
;
MMPI
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Multivariate Analysis
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Neoplasm Metastasis
;
Patient Selection*
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Phenotype
;
Population Characteristics
;
Prognosis
;
Stomach Neoplasms*