Hwa Jung Sung

Yonsei University Hospital, Seoul, Seoul, South Korea

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Publications (35)82.6 Total impact

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    ABSTRACT: Several reports have shown a better prognosis in gastric cancer patients who are positive for Helicobacter pylori (HP) infection compared with negative cases. However, there are currently no studies that investigate the relationship between HP infection and the effects of chemotherapy in gastric cancer patients. In this study, we report the relationship between HP infection and chemotherapy effects in patients with advanced or metastatic gastric cancer. Sixty-one patients with advanced or metastatic gastric cancer were enrolled in this study. Biopsies were conducted around the tumor site to determine HP status. Patients were then treated with combination 5-FU and cisplatin-based chemotherapy. And we compared chemotherapy response rate and overall survival rate between HP infection group and without HP infection group. Twelve of 18 patients with HP infection (66.7 %) and 9 of 42 patients without HP infection (21.4 %) showed a partial response to chemotherapy (Chi square P = 0.001). Patients with HP infection had a median survival time of 13 months (95 % CI, 6.9-19.1 months), which was significantly longer than that of patients without HP infection (9 months; P = 0.027, log-rank test). Patients with advanced or metastatic gastric cancer with concomitant HP infection had a better response to chemotherapy and had an improved overall prognosis compared with patients without HP infection. Further studies are warranted to confirm these findings.
    Cancer Chemotherapy and Pharmacology 08/2012; 70(4):555-8. · 2.80 Impact Factor
  • Clinical neurology and neurosurgery 05/2012; · 1.30 Impact Factor
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    ABSTRACT: Granulysin (cytolytic molecules of cytotoxic T lymphocytes and natural killer cells) is synthesized as cytosolic 9-kDa and secretary 15-kDa isoforms. We evaluated the prognostic significance of the pretreatment serum level of 15-kDa granulysin in patients with diffuse large B cell lymphoma (DLBCL). A retrospective analysis was conducted on 88 DLBCL patients treated homogeneously with standard chemotherapy. The granulysin level was quantified in pretreatment samples. The granulysin level in DLBCL patients was significantly lower than that in healthy controls (522 ± 496 vs. 1,945 ± 1,696 pg/ml; p < 0.0001), and the level in patients who experienced recurrence within 3 years was significantly lower than that of patients without recurrence (305 ± 337 vs. 720 ± 607 pg/ml; p = 0.001). Patients with granulysin levels higher than the median level showed significantly longer progression-free and overall survival according to univariate analysis (p = 0.031 and p = 0.014, respectively). In multivariate analysis, the granulysin level was an independently significant prognostic factor of overall survival (p = 0.018; hazard ratio, 0.521; 95% confidence interval, 0.188-0.841). Pretreatment serum level of 15-kDa granulysin may be a valuable prognostic marker in DLBCL patients treated with standard chemotherapy.
    Acta Haematologica 05/2011; 126(2):79-86. · 0.89 Impact Factor
  • Leukemia & lymphoma 03/2011; 52(3):528-30. · 2.61 Impact Factor
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    ABSTRACT: In the culture system using human feeder cells, the mechanism through which these cells support undifferentiated growth of embryonic stem cells (ESCs) has not been well investigated. Here, we explored the mechanisms of 3 kinds of human feeder cells, including human placental cells from the chorionic plate, human bone marrow stromal cells, and human foreskin fibroblasts. First, we determined that undifferentiated growth of 2 kinds each of human (H1 and HSF6) and mouse (D3 and CE3) ESCs was possible in all human feeder cell types tested (human placental cells, human bone marrow stromal cells, and human foreskin fibroblasts), without the need for exogenous cytokine supplementation including basic fibroblast growth factor (bFGF) and leukemia inhibitory factor. We then prepared their corresponding endogenous bFGF-knockout feeders using siRNA and tried to maintain human and mouse ESCs in their undifferentiated state; however, neither human nor mouse ESCs could be maintained in bFGF-knockout human feeder cells. The expressions of stemness markers such as Oct-4 and Nanog were significantly decreased in the bFGF-knockout group compared with those in the controls, and differentiation had already occurred, despite the undifferentiated morphologic appearance of the ESCs. In conclusion, human feeder cells are able to support the undifferentiated growth of human and mouse ESCs via bFGF synthesis. Further, a bFGF-dependent pathway might be crucial for maintaining the undifferentiated characteristics of mouse and human ESCs.
    Stem cells and development 01/2011; 20(11):1901-10. · 4.15 Impact Factor
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    ABSTRACT: This study was done to evaluate the stemness of human mesenchymal stem cells (hMSCs) derived from placenta according to the development stage and to compare the results to those from adult bone marrow (BM). Based on the source of hMSCs, three groups were defined: group I included term placentas, group II included first-trimester placentas, and group III included adult BM samples. The stemness was evaluated by the proliferation capacity, immunophenotypic expression, mesoderm differentiation, expression of pluripotency markers including telomerase activity. The cumulative population doubling, indicating the proliferation capacity, was significantly higher in group II (P<0.001, 31.7±5.8 vs. 15.7±6.2 with group I, 9.2±4.9 with group III). The pattern of immunophenotypic expression and mesoderm differentiation into adipocytes and osteocytes were similar in all three groups. The expression of pluripotency markers including ALP, SSEA-4, TRA-1-60, TRA-1-81, Oct-4, and telomerase were strongly positive in group II, but very faint positive in the other groups. In conclusions, hMSCs from placentas have different characteristics according to their developmental stage and express mesenchymal stemness potentials similar to those from adult human BMs.
    Journal of Korean medical science 10/2010; 25(10):1418-26. · 0.84 Impact Factor
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    ABSTRACT: High-dose melphalan (200 mg/m(2)) with autologous stem cell transplantation (ASCT) is the standard treatment for young patients with multiple myeloma (MM). However, the response rates after ASCT are often unsatisfactory. We performed a pilot study by using bortezomib-melphalan as conditioning regimen for ASCT in Korean patients with MM. The conditioning regimen consisted of administration of intravenous infusion of bortezomib 1.0 mg/m(2) on days -4 and -1 and melphalan 50 mg/m(2) (day -4) and 150 mg/m(2) (day -1). In this study, we enrolled 6 newly diagnosed patients and 2 patients with relapse. The disease status of the 6 newly diagnosed patients at ASCT was as follows: 1 complete remission (CR), 1 very good partial remission (VGPR), and 4 partial remissions (PRs). The disease status of the 2 relapsed patients at ASCT was PR. All patients except 1 showed adequate hematologic recovery after ASCT. The median time for the absolute neutrophil counts to increase over 500/mm(3) was 13 days (range, 10-19 days). Six patients with VGPR or PR at the time of transplantation showed an improvement in response to CR after ASCT. The patients were followed up without any maintenance treatment after ASCT except 1 patient who died during ASCT. During the follow-up period, CR was maintained in 3 newly diagnosed patients, but the other 4 patients, including 2 newly diagnosed patients, relapsed. Conditioning regimen consisting of bortezomib and melphalan may be effective for ASCT in MM; however, the feasibility of this regimen should be further evaluated in large study populations.
    The Korean journal of hematology 09/2010; 45(3):183-7.
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    ABSTRACT: The use of a mouse embryonic fibroblast (MEF) feeder for culture of embryonic stem cells (ESCs) is a widely accepted method, regardless of the ESCs' origin and type. In this study, we performed the undifferentiated propagation of human ES cell lines (hESCs, H1, and HSF6) and mouse ES cell lines (mESCs, D3, and CE3), which were previously maintained on an MEF feeder, using human placenta-derived fibroblast-like cell (HPC) feeders originated from chorionic villi of women who had undergone therapeutic abortion due to known maternal disease that is aggravated by pregnancy. Moreover, we tried to introduce the HPC feeder for the establishment of inducible pluripotent stem cells (iPSCs) from human placental mesenchymal stem cells (MSCs). On the HPC feeder we were able to propagate ESCs and iPSCs colonies as an undifferentiated state up to the 50th passage and 20th passage, respectively. Maintenance of undifferentiated ESCs was identified by the expression of ALP, SSEA-1, SSEA-4, TRA-81, TRA-60, Oct-4, Nanog, or Rex-1. Also, addition of leukemia inhibitory factor was not required for undifferentiated propagation of mESCs on the HPC feeder. The efficiency and expression of three germ layer markers of embryoid bodies (EBs) from ESCs were satisfactory in both the MEF and HPC group. EBs formed from iPSCs were scant, and differentiation to the three germ layers was identifiable by reverst transcription-polymerase chain reactio (RT-PCR) only in the HPC group. In conclusion, the HPC feeder can efficiently support the undifferentiated propagation of hESCs, mESCs, and iPSCs, suggesting that human placenta may be a useful source of universal feeder cells for hESC, mESC, and iPSC culture.
    Cellular reprogramming. 06/2010; 12(3):315-28.
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    ABSTRACT: In order for human embryonic stem cells (hESCs) to be cultured on mouse embryonic fibroblast (MEFs) feeder cells, continuous basic fibroblast growth factor (bFGF) supplementation is required. However, the role of bFGF in a culture system using human-derived feeder cells has not been evaluated until now. In this study, we propagated the widely used hESC lines, H1 and HSF6, on human placenta-derived feeder cells (HPCs) without exogenous bFGF supplementation, and were able to propagate hESCs on HPC feeders up to 50 passages. The absence of bFGF in culture media did not interrupt the undifferentiated propagation and the expression of pluripotent stem cell markers ALP, SSEA-4, TRA-60, Oct-4, Nanog, and Rex-1, as well as the formation of embryoid bodies (EBs) and their differentiation potential. In contrast, hESCs cocultured with MEF feeders could not propagate and form EBs without exogenous bFGF supplementation. Expression of bFGF and the activation of the ERK1/2-c-Fos/c-Jun pathway, which is known as the signaling pathway of bFGF, were identifiable not only in hESCs cultured in bFGF-containing media regardless of feeder cell type, but also in hESCs cocultured with HPC feeder cells in media without bFGF. These findings may support the hypothesis that HPC feeder cells enhance endogenous bFGF production and activation of the ERK1/2-c-Fos/c-Jun pathway, which suggests that HPCs have an additional advantage in their hESC propagation compared with MEF.
    Stem cells and development 03/2010; 19(11):1713-22. · 4.15 Impact Factor
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    ABSTRACT: Published studies on the association between the progesterone receptor gene +331 G/A polymorphism and breast cancer risk are inconclusive, and meta-analysis is required to verify the association. Six studies, including a total of 6,849 cases and 6,589 controls, were subjected to meta-analysis. When all eligible subjects were pooled for meta-analysis, the AG + AA variant genotype was not associated with a significantly elevated breast cancer risk [odds ratio (OR) = 1.11; 95% confidence interval (95%CI) = 0.99-1.24; P = 0.071]. However, subgroup analysis revealed that the AG + AA variant genotype was associated with an increased risk of breast cancer in American (OR = 1.32; 95%CI = 1.10-1.58; P = 0.003), but not in European or Australian. We could carefully suggest that the progesterone receptor promoter +331 G/A variant polymorphism might increase breast cancer risk, and this effect appeared to be more prominent in Americans than in Europeans and Australians.
    Cancer genetics and cytogenetics 01/2010; 196(2):194-7. · 1.54 Impact Factor
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    ABSTRACT: Recently, third-line chemotherapy for advanced non-small cell lung cancer (NSCLC) was accepted as a reasonable therapeutic option in patients with a favorable performance status. In practice, however, palliative chemotherapy has been performed for patients with a favorable performance status, even after third-line chemotherapy. Although multiple cycles of palliative chemotherapy were performed for these patients, there are little data of observation for courses of treatment from first-line to the last chemotherapy. We reviewed the courses of treatment for 82 patients with advanced NSCLC that had been admitted for platinum-based chemotherapy as a first-line treatment. Additional cycles of palliative chemotherapy were provided as monotherapy, based on the attending physician's decision considering patient performance status and toxicity after disease progression for previous chemotherapy. The median number of chemotherapy lines and cycles were 2 and 7, respectively, from first-line to the last chemotherapy. The median overall survival was 24 months in the response group of first-line chemotherapy, compared to 15 months for the entire study group. In the response group, the median number of chemotherapy cycles was 15 and patients received a median of 3 lines of chemotherapy. A total of 33 patients were candidate third-line chemotherapy or more. The median survival was 23 months for patients treated with more than third-line chemotherapy, compared to 7 months for patients treated with less than second-line chemotherapy. We conclude that long-standing chemotherapy is not beneficial to all NSCLC patients. However, patients with a favorable response to first-line chemotherapy tend to receive a higher number and more cycles of chemotherapy than the non-response group. Furthermore, multi-line chemotherapy appears to increase survival in the response group. Further studies will be needed to confirm these results.
    Oncology letters 01/2010; 1(1):51-55. · 0.24 Impact Factor
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    ABSTRACT: The breast is a rare extranodal site of non-Hodgkin lymphoma, and primary breast lymphoma (PBL) has been arbitrarily defined as disease localized to one or both breasts with or without regional lymph nodes involvement. The aim of this study was to evaluate the clinical outcomes in patients with diffuse large B cell lymphoma (DLBCL) and breast involvement, and to find the criteria of PBL reflecting the outcome and prognosis. We retrospectively analyzed data from 68 patients, newly diagnosed with DLBCL and breast involvement at 16 Korean institutions between January 1994 and June 2009. Median age at diagnosis was 48 years (range, 20-83 years). Forty-three (63.2%) patients were PBL according to previous arbitrary criteria, sixteen (23.5%) patients were high-intermediate to high risk of international prognostic index. The patients with one extranodal disease in the breast (OED) with or without nodal disease were 49 (72.1%), and those with multiple extranodal disease (MED) were 19 (27.9%). During median follow-up of 41.5 months (range, 2.4-186.0 months), estimated 5-year progression-free survival (PFS) was 53.7 +/- 7.6%, and overall survival (OS) was 60.3 +/- 7.2%. The 5-year PFS and OS was significantly higher for patients with the OED group than those with the MED group (5-year PFS, 64.9 +/- 8.9% vs. 27.5 +/- 11.4%, p = 0.001; 5-year OS, 74.3 +/- 7.6% vs. 24.5 +/- 13.0%, p < 0.001). In multivariate analysis, MED (hazard ratio [HR], 3.61; 95% confidence interval [CI], 1.07-12.2) and fewer than four cycles of systemic chemotherapy with or without local treatments (HR, 4.47; 95% CI, 1.54-12.96) were independent prognostic factors for worse OS. Twenty-five (36.8%) patients experienced progression, and the cumulative incidence of progression in multiple extranodal sites or other than breasts and central nervous system was significantly different between the OED group and the MED group (5-year cumulative incidence, 9.7 +/- 5.4% vs. 49.0 +/- 15.1%, p = 0.001). Our results show that the patients included in OED group, reflecting different treatment outcome, prognosis and pattern of progression, should be considered as PBL in the future trial. Further studies are warranted to validate our suggested criteria.
    BMC Cancer 01/2010; 10:321. · 3.33 Impact Factor
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    ABSTRACT: Lymphomatoid granulomatosis (LYG) is a rare angiocentric and angiodestructive lymphoproliferative disease characterized by Epstein-Barr virus-positive B cells admixed with reactive T cells. LYG most commonly affects the lung but can also involve other extrapulmonary sites. Pulmonary LYG usually presents as multiple pulmonary nodules with rapid progression and excavation. It can mimic various infectious diseases, vasculitis or metastatic malignancy and is difficult to be diagnosed clinically. Standard treatment for LYG has not yet been established. Despite combination chemotherapy, the overall prognosis is poor. Recently, anti-CD20 monoclonal antibody, rituximab, has been used to treat LYG. We report the case of a 70-year-old male patient with pulmonary LYG, who showed rapid remission of the disease after combination chemotherapy with rituximab.
    Chemotherapy 09/2009; 55(5):386-90. · 2.07 Impact Factor
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    ABSTRACT: We analyzed the prognostic factors from 259 cases of febrile neutropenia occurring in 137 patients with hematologic disease. Based on multivariate analysis, significant prognostic factors are recovery of neutropenia, respiratory infection, baseline serum albumin, baseline bicarbonate, baseline CRP, and CRP on the fifth day after antibiotic treatment. From these variables, we derived a predictive model for the prognosis of febrile neutropenia using baseline serum albumin, bicarbonate, and CRP, which could be easily checked before chemotherapy. Further studies in prospective setting are needed for the validation of this model.
    Leukemia research 09/2009; 34(3):294-300. · 2.36 Impact Factor
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    ABSTRACT: Our aim in this paper is to verify the efficacy and safety of a epirubicin and docetaxel salvage regimen for anthracycline sensitive metastatic breast cancer patients who have relapsed after anthracycline-containing adjuvant therapy. Thirty-two metastatic breast cancer patients were treated with epirubicin and docetaxel every 21days. Of the 31 evaluable patients, there were 13/31 (41.9%) partial responses and no complete responses. Median time to progression was 12months (95% CI, 4–60months) and median survival duration was 41months (95% CI, 1.2–80.8months). According to the Cox model, ECOG performance and response group were statistically significant variables, and visceral metastasis was a borderline significant variable with regards to overall survival. Although this salvage regimen showed a high rate of hematologic toxicities, it was a relatively active regimen with manageable toxicities and no cardiac dysfunction. We propose that this salvage regimen could be carefully used in anthracycline sensitive metastatic breast cancer patients who have relapsed after anthracycline-containing adjuvant therapy.
    Investigational New Drugs 02/2009; 27(1):67-73. · 3.50 Impact Factor
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    ABSTRACT: The role of 90K and galectin-3 in cell-to-extracellular matrix adhesion and tumor metastasis has been reported, but little is known about their role in the prognosis and extranodal involvement of diffuse large B-cell lymphomas (DLBCL). Thus, we measured serum 90K concentration by enzyme-linked immunosorbent assay and tissue expression of galectin-3 by immunohistochemistry in newly diagnosed DLBCL patients. The mean serum 90K concentration was higher in DLBCL than in healthy controls (1,408.81 +/- 89.45 vs. 980.94 +/- 58.69 ng/ml, p = 0.036). High serum 90K (median value >or=1,249.50 ng/ml) and high galectin-3 expression (grade 3 positive staining in >75% of cells) showed a significant association with stage III/IV, >or=2 extranodal involvements and risk of high/high-intermediate international prognostic index (p < 0.05). The complete response (CR) rate (86.9%, 20/23) in the low 90K group was higher than in the high 90K group (56.5%, 13/23). Among 14 patients with high galectin-3 expression, only 6 patients showed CR (42.9%). The time to progression and overall survival were shorter in the group with high 90K and galectin-3 expression (p < 0.05). In conclusion, serum 90K and galectin-3 expression might be useful markers to indicate the extent of lymphoma involvement and prognosis in DLBCL.
    Acta Haematologica 01/2009; 120(4):211-6. · 0.89 Impact Factor
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    Tuberculosis and Respiratory Diseases 01/2009; 66(2).
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    ABSTRACT: 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. 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. 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). 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.
    Cancer Research and Treatment 12/2008; 40(4):178-83. · 1.96 Impact Factor
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    ABSTRACT: Arginine deiminase (ADI) is known to be an inducer of apoptosis in vitro and an anti-tumor agent in vivo in some cancers. ADI causes the enzymatic depletion of arginine which may inhibit nitric oxide (NO) synthesis. However, the effect of ADI treatment on NO synthesis has not been clearly elucidated. With the goal of understanding the role of ADI in NO synthesis, we used the Ramos human lymphoma cell line, which is known to be ADI-sensitive. After determining an optimal experimental ADI concentration (0.001 U/ml), we studied the effects of ADI treatment when combined with different concentrations of the extrinsic NO donor, sodium nitroprusside (SNP) (i.e., control, ADI only, ADI with 10 microM/ml SNP, ADI with 50 microM/ml SNP, and ADI with 100 microM/ml SNP). An MTT assay was used to assess cell survival after treatment, nitric oxide assays to determine nitrite levels and Western blot analysis to determine the expression of the NO mediators, NFkappaB and Bcl-X L. Interestingly, we found that the extrinsic NO donor only partially reversed ADI-induced inhibition of cell growth in a dose-dependent pattern and resulted in an induction of NFkappaB and Bcl-X L expression. In conclusion, we suggest that there might be an association between reversal of cell growth inhibition by extrinsic NO donor with Bcl-X L and NFkappaB expression in ADI-treated Ramos cell.
    Investigational New Drugs 07/2008; 26(3):277-82. · 3.50 Impact Factor
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    ABSTRACT: We performed a single-institution retrospective study to evaluate the efficacy and toxicities of oxaliplatin, 5-fluorouracil (5-FU), leucovorin (LV) combination chemotherapy as salvage treatment in patients with metastatic or advanced gastric cancer. Sixty-two patients with advanced gastric cancer previously treated were eligible for the study. Patients received oxaliplatin 100 mg/m(2) and LV 100 mg/m(2) (2-h intravenous infusion) followed by 5-FU 2,400 mg/m(2) (46-h continuous infusion) every 2 weeks, and responses were assessed after every three cycles. Fifty-nine out of 62 patients were assessable for response. Among them, 46 patients had previously been treated with cisplatin based chemotherapy. Patients had a median age of 57 years (range 32-76 years), 72.6% had an Eastern Cooperative Oncology Group performance status of 0 or 1. Total 296 courses of chemotherapy were administered as second-line (67.7%) or third-line (27.4%), and the median courses per patient was three cycles. Out of 59 evaluable patients, 14 partial responses were observed (overall response rate, 22.6%). Stable disease was observed in 22 patients (35.5%), and progressive disease in 23 patients (37.1%). The median response duration, time to progression, and overall survival were 2.3, 3.0, and 8.0 months, respectively. The major toxicities were neutropenia, mucositis, and peripheral neuropathy. Grade 3 or 4 hematologic toxicities included neutropenia in nine patients (14.5%) and thrombocytopenia in one patient (1.6%). Other grade 3 or 4 toxicities included mucositis in one patient (1.6%) and vomiting in two patients (3.2%). Grade 1 or 2 peripheral neuropathy were observed in 18 patients (29.0%), however there were no cases of grade 3 or 4 peripheral neuropathy and no treatment-related deaths. The combination of oxaliplatin, 5-FU and LV was effective and safe salvage chemotherapy in advanced gastric cancer patients.
    Cancer Chemotherapy and Pharmacology 05/2008; 63(3):433-9. · 2.80 Impact Factor

Publication Stats

175 Citations
82.60 Total Impact Points

Institutions

  • 2007–2011
    • Yonsei University Hospital
      • Department of Internal Medicine
      Seoul, Seoul, South Korea
    • University of Seoul
      Sŏul, Seoul, South Korea
    • Konkuk University Medical Center
      Changnyeong, South Gyeongsang, South Korea
  • 2003–2010
    • Seoul Medical Center
      Sŏul, Seoul, South Korea
  • 2005–2009
    • Korea University
      • Department of Internal Medicine
      Seoul, Seoul, United States
  • 2006
    • Konkuk University
      • Department of Internal medicine
      Sŏul, Seoul, South Korea