Comparison of the Data of a Next-Generation Sequencing Panel from K-MASTER Project with That of Orthogonal Methods for Detecting Targetable Genetic Alterations / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#K-MASTER project is a Korean national precision medicine platform that screened actionable mutations by analyzing next-generation sequencing (NGS) of solid tumor patients. We compared gene analyses between NGS panel from the K-MASTER project and orthogonal methods. @*Materials and Methods@#Colorectal, breast, non–small cell lung, and gastric cancer patients were included. We compared NGS results from K-MASTER projects with those of non-NGS orthogonal methods (KRAS, NRAS, and BRAF mutations in colorectal cancer [CRC]; epidermal growth factor receptor [EGFR], anaplastic lymphoma kinase [ALK] fusion, and reactive oxygen species 1 [ROS1] fusion in non–small cell lung cancer [NSCLC], and Erb-B2 receptor tyrosine kinase 2 (ERBB2) positivity in breast and gastric cancers). @*Results@#In the CRC cohort (n=225), the sensitivity and specificity of NGS were 87.4% and 79.3% (KRAS); 88.9% and 98.9% (NRAS); and 77.8% and 100.0% (BRAF), respectively. In the NSCLC cohort (n=109), the sensitivity and specificity of NGS for EGFR were 86.2% and 97.5%, respectively. The concordance rate for ALK fusion was 100%, but ROS1 fusion was positive in only one of three cases that were positive in orthogonal tests. In the breast cancer cohort (n=260), ERBB2 amplification was detected in 45 by NGS. Compared with orthogonal methods that integrated immunohistochemistry and in situ hybridization, sensitivity and specificity were 53.7% and 99.4%, respectively. In the gastric cancer cohort (n=64), ERBB2 amplification was detected in six by NGS. Compared with orthogonal methods, sensitivity and specificity were 62.5% and 98.2%, respectively. @*Conclusion@#The results of the K-MASTER NGS panel and orthogonal methods showed a different degree of agreement for each genetic alteration, but generally showed a high agreement rate.

Randomized Phase III Trial of Irinotecan Plus Cisplatin versus Etoposide Plus Cisplatin in Chemotherapy-Naïve Korean Patients with Extensive-Disease Small Cell Lung Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: This randomized phase III study was designed to compare the efficacy and safety of irinotecan plus cisplatin (IP) over etoposide plus cisplatin (EP) in Korean patients with extensive-disease small-cell lung cancer (SCLC). MATERIALS AND METHODS: Patients were randomly assigned to receive IP, composed of irinotecan 65 mg/m2 intravenously on days 1 and 8+cisplatin 70 mg/m2 intravenously on day 1 every 3 weeks, or EP, composed of etoposide 100 mg/m2 intravenously on days 1, 2, 3+cisplatin 70 mg/m2 intravenously on day 1, every 3 weeks for a maximum of six cycles, until disease progression, or until unacceptable toxicity occurred. The primary endpoint was overall survival. RESULTS: A total of 362 patients were randomized to IP (n=173) and EP (n=189) arms. There were no significant differences between IP and EP arms for the median overall survival (10.9 months vs. 10.3 months, p=0.120) and the median progression-free survival (6.5 months vs. 5.8 months, p=0.115). However, there was a significant difference in response rate (62.4% vs. 48.2%, p=0.006). The pre-planned subgroup analyses showed that IP was associated with longer overall survival in male (11.3 months vs. 10.1 months, p=0.036), < 65 years old (12.7 months vs. 11.3 months, p=0.024), and Eastern Cooperative Oncology Group performance status 0/1 (12.4 months vs. 10.9 months, p=0.040) patient groups. The severity of treatment-related adverse events such as grade 3/4 anemia, nausea and diarrhea was more frequent in patients treated with IP. CONCLUSION: The IP chemotherapy did not significantly improve the survival compared with EP chemotherapy in Korean patients with extensive-disease SCLC.

National Lung Cancer Screening Program in Korea: More Harm Than Good

Although the result of low dose computed tomography (LDCT) screening for high risk smoker for lung cancer (National Lung Screening Trial, NLST) showed 20% of lower lung cancer death compare to chest X-ray screening, which published in 2011, after more than 8 years passed, no European or Asian country has implemented organized lung cancer screening with LDCT, and there are no National Lung Cancer Screening Program globally. In United States, where LDCT lung screening has become standard procedure, the screening rate is extremely low, less than 5%. That is because in spite of the considerable the benefit of the screening, the harms of screening; specifically, most notably due to the high level of false positives, and physical, psychological, and economical burdens. Recently the controversies regarding the harms of LDCT lung screening has been increasingly debated. Also, the novel strategies, such as artificial intelligence and volumetric measurement of suspicious nodules has been adopted for recently launched lung cancer screening clinical trials. However, amid of skeptical opinions increasing globally, Korean Government recently decided to include LDCT lung cancer screening as national cancer screening program, becoming Korea as the first and the only national lung cancer screening program worldwide. Without randomized trial proven to be effective for Korea population, hurried implementation of national lung cancer screening program could have more harmful effect than benefit in terms of public health perspectives.

National Lung Cancer Screening Program in Korea: More Harm Than Good

Although the result of low dose computed tomography (LDCT) screening for high risk smoker for lung cancer (National Lung Screening Trial, NLST) showed 20% of lower lung cancer death compare to chest X-ray screening, which published in 2011, after more than 8 years passed, no European or Asian country has implemented organized lung cancer screening with LDCT, and there are no National Lung Cancer Screening Program globally. In United States, where LDCT lung screening has become standard procedure, the screening rate is extremely low, less than 5%. That is because in spite of the considerable the benefit of the screening, the harms of screening; specifically, most notably due to the high level of false positives, and physical, psychological, and economical burdens. Recently the controversies regarding the harms of LDCT lung screening has been increasingly debated. Also, the novel strategies, such as artificial intelligence and volumetric measurement of suspicious nodules has been adopted for recently launched lung cancer screening clinical trials. However, amid of skeptical opinions increasing globally, Korean Government recently decided to include LDCT lung cancer screening as national cancer screening program, becoming Korea as the first and the only national lung cancer screening program worldwide. Without randomized trial proven to be effective for Korea population, hurried implementation of national lung cancer screening program could have more harmful effect than benefit in terms of public health perspectives.

Tolerability and Outcomes of First-Line Pemetrexed-Cisplatin Followed by Gefitinib Maintenance Therapy Versus Gefitinib Monotherapy in Korean Patients with Advanced Nonsquamous Non-small Cell Lung Cancer: A Post Hoc Descriptive Subgroup Analysis of a Rand / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: We recently reported on a randomized, open-label, phase 3 trial comparing pemetrexed-cisplatin chemotherapy followed by gefitinib maintenance therapy (PC/G) with gefitinib monotherapy in patients with non-small cell lung cancer (NSCLC). Here, we report on a post hoc subgroup analysis of that study assessing the demographics and disposition of the Korean patient subgroup, and comparing the tolerability of PC/G and gefitinib monotherapy and the tumor response with respect to epidermal growth factor receptor (EGFR) status. MATERIALS AND METHODS: Patients, who were ≥ 18 years, chemonaïve, Korean, light ex-smokers/never-smokers with advanced NSCLC, were randomly assigned (1:1) to PC/G or gefitinib monotherapy. Treatment-emergent adverse events (TEAEs) were graded, and tumor response was measured as change in lesion sum from baseline at best response. The study was registered with ClinicalTrials. gov, NCT01017874. RESULTS: Overall, 111 Korean patients were treated (PC/G, 51; gefitinib, 60). Between-arm characteristics were balanced and similar to those of the overall population. Treatment discontinuations due to adverse events were low (PC/G: 1, 2.0%; gefitinib: 7, 11.7%). Overall, 92 patients (82.9%) reported ≥ 1 TEAE (PC/G, 44; gefitinib, 48); few patients (PC/G, 16; gefitinib, 7) reported severe TEAEs; the most frequent was neutropenia (PC/G arm) and elevated alanine aminotransferase (gefitinib arm). The lesion sum was decreased by PC/G treatment in most patients, regardless of EGFR mutation status, while gefitinib monotherapy reduced the lesion sum in EGFR-positive patients but had no effect in EGFR-negative patients. CONCLUSION: Our results confirm that both PC/G and gefitinib were well tolerated in Korean patients, regardless of EGFR status; however, patients with EGFR wild-type NSCLC may not benefit from gefitinib monotherapy.

Novel Germline Mutation of BRCA1 Gene in a 56-Year-Old Woman with Breast Cancer, Ovarian Cancer, and Diffuse Large B-Cell Lymphoma / Journal of the Korean Cancer Association, 대한암학회지

We report a case of a 56-year-old woman with breast cancer, ovarian cancer, and diffuse large B-cell lymphoma with a BRCA1 gene mutation. Evidence is mounting that there is a large increase in the risk for hematologic malignancies among patients with genetic changes in the BRCA pathways. The genomic analysis demonstrated a frameshift mutation in the BRCA1 gene: 277_279delinsCC (Phe93fs). It is a novel BRCA1 mutation that has never been reported, and caused malignant lymphoma as well as breast and ovarian cancer.

Dose KRAS Mutation Status Affect on the Effect of VEGF Therapy in Metastatic Colon Cancer Patients? / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Mutations affecting the KRAS gene are an established negative predictor for anti-epidermal growth factor receptor (anti-EGFR) therapies in metastatic colorectal cancer (CRC). However, the role of KRAS mutation as a biomarker for anti-vascular endothelial growth factor (VEGF) remains controversial. MATERIALS AND METHODS: We analyzed retrospective data from 32 CRC patients who were available for KRAS mutation status and received cytotoxic chemotherapy plus bevacizumab as a first-line therapy. Six of 32 patients received anti-EGFR therapies. We used KRAS mutation status as a predictive or prognostic factor in CRC patients receiving bevacizumab. RESULTS: We observed mutations in KRAS in 59.4% of patients. Bevacizumab was used in combination with oxaliplatin based regimens. There was no significant difference for progression free survival (PFS) and overall survival (OS) in patients with oxaliplatin based cytotoxic chemotherapy plus bevacizumab according to the status of KRAS mutation. After first-line therapy, 28 patients (87.5%) received second-line therapy. In univariate analysis, KRAS mutations did not have a major prognostic value for PFS (hazard ratio, 1.007; 95% confidence interval [CI], 0.469 to 2.162; p>0.05) or OS (hazard ratio, 0.548; 95% CI, 0.226 to 1.328; p>0.05). In addition, anti-EGFR therapies did not affect the impact on OS. CONCLUSION: KRAS mutation is neither a predictive for bevacizumab nor a prognostic for OS in CRC patients receiving anti-VEGF therapy.

Modified MVAC as a Second-Line Treatment for Patients with Metastatic Urothelial Carcinoma after Failure of Gemcitabine and Cisplatin Treatment / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: There is no established standard second-line chemotherapy for patients with advanced or metastatic urothelial carcinoma (UC) who failed gemcitabine and cisplatin (GC) chemotherapy. This study was conducted in order to investigate the efficacy and toxicity of modified methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) in patients with metastatic UC previously treated with GC. MATERIALS AND METHODS: We retrospectively analyzed 28 patients who received modified MVAC between November 2004 and November 2012. All patients failed prior, first-line GC chemotherapy. RESULTS: The median age of patients was 64.0 years (range, 33.0 to 77.0 years), and 23 (82.1%) patients had an Eastern Cooperative Oncology Group performance status of 0 or 1. The overall response rate and the disease control rate were 36.0% and 64.0%, respectively. After a median follow-up period of 38 weeks (range, 5 to 182 weeks), median progression free survival was 21.0 weeks (95% confidence interval [CI], 6.3 to 35.7 weeks) and median overall survival was 49.0 weeks (95% CI, 18.8 to 79.3 weeks). Grade 3 or 4 hematological toxicities included neutropenia (n=21, 75.0%) and anemia (n=9, 32.1%). Grade 3 or 4 non-hematological toxicities did not occur and there was no treatment-related death. CONCLUSION: Modified MVAC appears to be a safe and active chemotherapy regimen in patients with stable physical status and adequate renal function after GC treatment.

Impact of KRAS Mutation Status on Outcomes in Metastatic Colon Cancer Patients without Anti-Epidermal Growth Factor Receptor Therapy / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Activating mutation of the KRAS oncogene is an established negative predictor for anti-epidermal growth factor receptor (anti-EGFR) therapies in metastatic colorectal cancer (CRC). However, KRAS mutation as a prognostic factor of survival outcome remains controversial in CRC, independent of anti-EGFR therapies. MATERIALS AND METHODS: We conducted a retrospective analysis of 103 CRC patients who were available for evaluation of KRAS mutation status. None of the patients analyzed had received anti-EGFR therapies. The role of KRAS mutation status was evaluated as a predictive factor for oxaliplatin or irinotecan and as a prognostic factor in CRC patients who did not receive anti-EGFR therapies. RESULTS: Mutations in KRAS were observed in 48.5% of patients. The response for oxaliplatin- (p=0.664) and irinotecan-based (p=0.255) cytotoxic chemotherapy did not differ according to the KRAS mutation status. In addition, no significant difference in progression free survival (PFS; oxaliplatin, p=0.583 and irinotecan, p=0.426) and overall survival (OS; p=0.258) was observed between the wild and mutant type of the KRAS gene. In univariate and multivariate analyses, KRAS mutations did not have a major prognostic value regarding PFS (oxaliplatin: hazard ratio, 0.892; 95% confidence interval [CI], 0.590 to 1.347; p=0.586 and irinotecan: hazard ratio, 0.831; 95% CI, 0.524 to 1.319; p=0.433) or OS (hazard ratio, 0.754; 95% CI, 0.460 to 1.236; p=0.263). In addition, anti-vascular endothelial growth factor therapies did not affect PFS to oxaliplatin or irinotecan and OS. CONCLUSION: KRAS mutation is not a prognostic marker for PFS to oxaliplatin or irinotecan and OS in CRC patients who did not receive anti-EGFR therapies.

Chemotherapy in Patients Older than or Equal to 75 Years with Advanced Non-small Cell Lung Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: As the number of elderly patients diagnosed with non-small cell lung carcinoma (NSCLC) increases, the number of these patients receiving chemotherapy also increases. However, limited data exists regarding the use of chemotherapy in advanced NSCLC patients who are 75 years of age or older. MATERIALS AND METHODS: Between May 2002 and October 2008, data for 48 advanced NSCLC patients who were 75 years of age or older who had been treated with chemotherapy were retrospectively analyzed. RESULTS: The median age of study participants at the time of first line chemotherapy was 76 years (range, 75 to 87 years) and their median Charlson comorbidity index was 2 (range, 1 to 4). Of the total 48 patients, 43 patients (90%) were treated by platinum-based doublet as a first line chemotherapy regimen. Median progression free survival for first line chemotherapy was 5.7 months (95% confidence interval [CI], 4.93 to 6.47 months) with an overall response rate of 33.3%. After first line chemotherapy, only 14 of the 48 patients (29.2%) received second line chemotherapy. The median overall survival (OS) for these patients was 8.2 months (95% CI, 4.44 to 11.96 months). Multivariate analysis results indicated that female gender and having received second-line or more chemotherapy were independent prognostic factors for increased OS for all 48 patients. Charlson Index was not a significant independent prognostic factor for survival. There were 9 treatment related deaths due to infectious causes (18.8%). CONCLUSION: Patients 75 years of age or older with advanced NSCLC may obtain clinical benefit from the administration of platinum-based doublet or single agent chemotherapy. However, oncologists must consider the aspect of safety in relation to the clinical benefits when managing this patient group.

An Association Study of Polymorphisms in JAK3 Gene with Lung Cancer in the Korean Population / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The genetic alteration of the janus kinases (JAKs), non-receptor tyrosine kinase, is related to the development of human cancers. However, little is known about how the sequence variation of JAK3 contributes to the development of lung cancer. This study investigated whether polymorphisms at the promoter region of the JAK3 gene are associated with the risk of lung cancer in the Korean population. MATERIALS AND METHODS: A total of 819 subjects, including 409 lung cancer patients and 410 healthy controls were recruited. The SNaPshot assay and polymerase chain reaction-restriction fragment length polymorphism analysis were used, and logistic regression analyses were performed to characterize the association between polymorphisms of JAK3 and lung cancer risk. RESULTS: Three polymorphisms (-672 G>A, +64 A>G and +227 G>A) of JAK3 were analyzed for large-scale genotyping (n=819). Statistical analyses revealed that polymorphisms and haplotypes in the JAK3 gene were not significantly associated with lung cancer. CONCLUSION: JAK3 gene was not significantly associated with the risk of lung cancer in the Korean population.

No Association between PIK3CA Polymorphism and Lung Cancer Risk in the Korean Population

The PIK3CA gene, oncogenic gene located on human chromosome 3q26.3, is an important regulator of cell proliferation, death, motility and invasion. To evaluate the role of PIK3CA gene in the risk of Korean lung cancer, genotypes of the PIK3CA polymorphisms (rs11709323, rs2699895, rs3729679, rs17849074 and rs1356413) were determined in 423 lung cancer patients and 443 normal controls. Statistical analyses revealed that the genotypes and haplotypes in the PIK3CA gene were not significantly associated with the risk of lung cancer in the Korean population, suggesting that these PIK3CA polymorphisms do not contribute to the genetic susceptibility to lung cancer in the Korean population.

No Association between Promoter Polymorphism of STK11 Gene and Lung Cancer Risk in the Korean Population / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Serine-threonine kinase11 (STK11) was originally identified in 1997 as the causative mutation that's responsible for Peutz-Jeghers Syndrome (PJS). Several recent studies have reported that the STK11 gene is an important human tumor suppressor gene in lung cancer. We evaluated the associations between the polymorphisms of the STK11 promoter region and the risk of lung cancer in 901 Koreans. MATERIALS AND METHODS: By direct sequencing, we first discovered three novel polymorphisms (-1,795 T>C, -981 C>T and -160 G>T) and four known polymorphisms (-1,580 C>T, -1,494 A>C, -881 A>G and -458 G>C) of the STK11 promoter region in 24 blood samples of 24 Korean lung cancer patients. Further genotype analyses were then performed on 443 lung cancer patients and 458 controls. RESULTS: We discovered three novel polymorphisms and we identified four known polymorphisms of the STK11 promoter region in a Korean population. Statistical analyses revealed that the genotypes and haplotypes in the STK11 gene were not significantly associated with the risk of lung cancer in a Korean population. CONCLUSION: This is the first study that's focused on the association of STK11 promoter polymorphisms and the risk of lung cancer in a Korean population. To evaluate the role of the STK11 gene for the risk of lung cancer, the genotypes of the STK11 promoter region (-1,795 T>C, -1,494 A>C and -160 G>T) were determined in 901 Koreans, yet the result revealed no significant difference between the lung cancer patients and the controls. These results suggest that the three promoter polymorphisms we studied are not important risk factors for the susceptibility to lung cancer in Koreans.

Discrepant Views of Korean Medical Oncologists and Cancer Patients on Complementary and Alternative Medicine / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: This study was designed to evaluate the communication gap between Korean medical oncologists and cancer patients on complementary and alternative medicine (CAM). MATERIALS AND METHODS: Cross sectional studies utilized the responses of 59 medical oncologists and 211 patients. To understand the communication gap, perceived reasons and nondisclosure of CAM use, reactions of physicians to disclosure, and expectations for CAM were analyzed. Data were compared with use of the chi- squared test. RESULTS: Both medical oncologists and patients were in accord that CAM use would privde the patients with a feeling of hope. The medical oncologists believed more often than patients to attribute CAM use for control over medical care decisions, for the treatment of an incurable disease or as a nontoxic approach (p<0.05). Regarding reasons for nondisclosure, medical oncologists were morelikely to think that physicians would not understand the use of CAM, discontinue treatment or disapprove of the use of CAM (p<0.0001). Patients attributed nondisclosure mainly to the lack of questioning about CAM. Medical oncologists were more likely to warn of the risks with CAM use and less likely to encourage the use of CAM than perceived by patients (p=0.01). Patients expected that CAM could cure disease, extend survival, relieve symptoms and improve the immune system or quality of life more often than medical oncologists (p<0.05). CONCLUSION: Given the discrepant views of medical oncologists and patients on the use of CAM, medical oncologists should be aware of the discrepancies and attempt to resolve any differences.

Clinical Factors Related to Suspected Second Primary Lung Cancer Development in Patients with Head and Neck Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The rate of second primary lung cancer development for patients with head and neck cancer (HNC) has been noted. The aim of our study was to evaluate the incidence and clinical features of suspected second primary lung cancer that developed in patients with primary HNC. MATERIALS AND METHODS: We conducted a retrospective study of 469 patients who were newly diagnosed with HNC at the Korea University Medical Center between January 2000 and December 2006. RESULTS: A total of 469 patients were included (389 men and 80 women). Eighteen patients (3.8%) had suspected second primary lung cancers. Statistically significant clinical variables for lung cancer development included the origin site for the primary HNC (oro-hypopharynx and larynx) (p=0.048), abnormal chest x-ray findings (p=0.027) and the histological HNC type (squamous cell carcinoma) (p=0.032). When the second primary lung cancers were combined with HNCs, the adjusted overall survival of patients with a second primary lung cancer was 16 months (p<0.001). CONCLUSIONS: Considering the relative risk factors for a second primary lung cancer developing in patients with HNC, advanced diagnostic tools, such as chest CT or PET CT scan, should be applied for the early detection of a second primary lung cancer.

Treatment Outcomes and Toxicities of ABVD Combination Chemotherapy Compared with CVPP in Hodgkin's Disease / 대한혈액학회지

BACKGROUND: We retrospectively evaluated the treatment outcomes and toxicities of Hodgkin's disease (HD) patients treated by ABVD (adriamycin, bleomycin, vinblastine, and dacarbazine) combination chemotherapy, and compared them with those of a historical group treated with a CVPP (cyclophosphamide, vinblastine, procarbazine, and prednisone) regimen. METHODS: The medical records of patients who had been diagnosed with HD histologically and treated by either ABVD or CVPP from 1997 to 2006 at the Korea University Medical Center were retrospectively reviewed. RESULTS: Thirty patients were eligible. Nineteen patients received ABVD and eleven patients were treated with CVPP. The response rates for ABVD and CVPP were 84.21% and 54.55%, respectively. Median overall survival was 43.17 months for ABVD and 43.27 months for CVPP (P=.570). Median event-free survival was 39.03 months for ABVD and 16.73 months for CVPP (P=.088). There was no significant difference in median survival or in event-free survival between the two regimens. Hematologic toxicities were significantly more common in the CVPP group than in the ABVD group. Grade 3 or 4 neutropenia was observed in 72.72% of the CVPP group and in 36.84% of the ABVD group (P=.050). CONCLUSION: ABVD for HD showed significantly lower hematologic toxicities and moderately better treatment outcomes than did CVPP.

Glucose Transporter-1 Expression in Squamous Cell Carcinoma of the Tongue / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Tumor cells are known to express hypoxia-related proteins such as glucose transporter-1 (Glut-1). These hypoxia-induced changes may allow tumor cells to survive under sustained hypoxic microenvironments, and the surviving tumor cell under hypoxia may develop a more aggressive phenotype and so result in a poor prognosis. MATERIALS AND METHODS: The Glut-1 expression was analyzed by immunohistochemistry, and its association with the prognosis was assessed in 60 patients with squamous cell carcinoma of the tongue. RESULTS: The Glut-1 expression was diffuse with a membranous pattern, and the median percentage of Glut-1 positive tumor cells was 60% (range: 0.0~90.0%). A high Glut-1 expression (the percentage of positive tumor cells > or = the median value, 60%) was associated with the location of primary lesion, lymph node metastasis status and disease stage (p<0.05). The expression of Glut-1 was correlated with the Ki-67 expression (r=0.406, p=0.001). Microvessel density, as represented by CD31 staining, was also correlated with the Glut-1 expression although its significance is weak (r=0.267, p=0.039). On the univariate analysis, the group with a high Glut-1 expression showed poorer overall survival than the group with a low Glut-1 expression (p<0.05). However, the Glut-1 expression failed to show any independent prognostic significance on the multivariate analysis. CONCLUSION: The expression of Glut-1 may be useful for predicting the prognosis and determining the treatment strategy for the management of squamous cell carcinoma of the tongue.

Evaluation of Web Sites on Treatment of Childhood and Adolescent Obesity / 대한소아소화기영양학회지

PURPOSE: The purpose of this study was to evaluate the quality and problems of Web sites for management of childhood and adolescent obesity. METHODS: We evaluated 203 Web sites identified from the search engine, Korean Yahoo, using the word of 'childhood and adolescent obesity'. 203 Web sites were classified according to medical institutions, health information Web sites, beauty shops. etc. We surveyed whether childhood and adolescent obesity distinguished with adult obesity was considered, or not. and researched the unique managements of childhood and adolescent obesity including the cardinal treatment. RESULTS: Of the 203 Web sites, 157(77.3%) provided detailed information about treatment of obesity, 46(22.7%) provided only simple information about one. The sites providing detailed information were composed of 52.2% of oriental medicine clinics, 35.0% of clinic and hospitals including pediatric hospitals. Distribution of the sites about management of childhood and adolescent obesity distinguished with adult's one was only 23% of oriental medicine clinics, but 93% of childrens hospitals. CONCLUSION: Without considering the speciality of childhood obesity, inaccurate information are distributing on internet web sites. It is necessary for concern and development of advertizing system on the internet distributing accurate information about treatment of childhood obesity.

Hematopoietic Differentiation of Embryoid Bodies Derived from the Human Embryonic Stem Cell Line SNUhES3 in Co-culture with Human Bone Marrow Stromal Cells

Human embryonic stem (ES) cells can be induced to differentiate into hematopoietic precursor cells via two methods: the formation of embryoid bodies (EBs) and co-culture with mouse bone marrow (BM) stromal cells. In this study, the above two methods have been combined by co-culture of human ES-cell-derived EBs with human BM stromal cells. The efficacy of this method was compared with that using EB formation alone. The undifferentiated human ES cell line SNUhES3 was allowed to form EBs for two days, then EBs were induced to differentiate in the presence of a different serum concentration (EB and EB/high FBS group), or co- cultured with human BM stromal cells (EB/BM co-culture group). Flow cytometry and hematopoietic colony-forming assays were used to assess hematopoietic differentiation in the three groups. While no significant increase of CD34+/CD45- or CD34+/CD38- cells was noted in the three groups on days 3 and 5, the percentage of CD34+/CD45- cells and CD34+/ CD38- cells was significantly higher in the EB/BM co-culture group than in the EB and EB/high FBS groups on day 10. The number of colony-forming cells (CFCs) was increased in the EB/BM co-culture group on days 7 and 10, implying a possible role for human BM stromal cells in supporting hematopoietic differentiation from human ES cell-derived EBs. These results demonstrate that co-culture of human ES-cell-derived EBs with human BM stromal cells might lead to more efficient hematopoietic differentiation from human ES cells cultured alone. Further study is warranted to evaluate the underlying mechanism.

Differentiation Culture of Hematopoietic Stem Cells from Embryonic Stem Cells / 대한혈액학회지

BACKGROUND: This study was designed to verify the effective culture condition for the differentiation of human hematopoietic stem cells from SNU-3 embryonic stem cell line. METHODS: Control group was that of which embryonic stem cells were directly cultured to LTC-IC assay. Study group was that of which an embryonic body manufactured from embryonic stem cells was cultured to LTC-IC assay. CD34+ cells were separated by MACS method at 1, 3, 5, 7, 10, 14, 21 days of LTC-IC assay in both groups. Thereafter, CD34+ cell were cultured to semisolid methyl-cellulose media to count CFUs. CD34+CD45- cell percentage was measured with FACS method at 5 days of LTC-IC assay. This study was repeated for 14 times. RESULTS: In control group, CD34+ cells were hardly separated in any period of LTC-IC assay. In study group, the median count of CD34+ cells was 0.7 (0.4-1.2)x10(4), 1.8 (1.4-2.6)x10(4), 0.6 (0.5-0.7)x10(4) and the median count of CFUs was 0.5 (0.2-0.8)x10(2), 1.0 (0.6-1.3)x10(2), 0.2(0.1-0.4)x10(2) at 3, 5, 7 days of LTC-IC assay, respectively. Median CFUs count per CD34+ cell was 0.0071, 0.0056, 0.0033 at 3, 5, 7 days of LTC-IC assay, respectively. In study group, the count of CD34+ cells and CFUs was significantly higher at 5 days of LTC-IC assay than at any other days (P<0.01). CFUs count per CD34+ cell was significantly higher at 3 days of LTC-IC assay than at any other days (P<0.01). CD34+CD45- cells detected by FACS method of study group(1.16%(0.92-1.97) was significantly higher than that of control group (0.09% (0.00-0.23)) (P<0.01). CONCLUSION: The differentiation of hematopoietic stem cells from SNU-3 embryonic stem cell line is effective in the condition of which an embryonic body manufactured from embryonic stem cells is cultured to LTC-IC assay. The period of which embryonic stem cells differentiate to hematopoietic stem cells is between 3 to 7 days of LTC-IC assay.