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Biomedical subjects

Seok Jin Kim

Publications and source records attributed to Seok Jin Kim.

At least 19 recordsLinked to original sources
PubMed2026

Daratumumab monotherapy for relapsed AL amyloidosis: a single center retrospective analysis.

PURPOSE: Treatment of relapsed AL amyloidosis remains challenging as patients frequently suffer from severe organ dysfunctions. Daratumumab, a cornerstone drug in multiple myeloma and newly diagnosed AL amyloidosis, has also shown promise in relapsed AL amyloidosis. MATERIALS AND METHODS: To assess the efficacy of daratumumab, we conducted a retrospective study of 40 patients who received daratumumab monotherapy in our prospective amyloidosis cohort. RESULTS: The median age of the cohort was 67&#xa0;years, and 31 patients were classified as stage III/IV by the Mayo 2012 guidelines and 32 patients as stage IIIa/IIIb by the European staging system. The overall hematologic and cardiac response rates were 72.5% and 42.4%, respectively. With median follow-up duration of 26.9&#xa0;months, the estimated median progression-free survival was 21.9&#xa0;months. Deep hematologic (p&#x2009;<&#x2009;0.001) and cardiac response (p&#x2009;=&#x2009;0.001) were associated with prolonged progression free survival. The duration of hematologic/cardiac responses were 26.2&#xa0;months and 27.8&#xa0;months, respectively. The median overall survival was 30.9&#xa0;months. Treatment was well tolerated, as with 3 patients experiencing grade 3-4 hematologic adverse events and 8 experiencing grade 3-4 non-hematologic adverse events. DISCUSSION: Our findings suggest that daratumumab monotherapy provides rapid and durable responses and is generally well tolerated in patients with relapsed AL amyloidosis.

AL amyloidosis↗
PubMed2006

uPAR expression under hypoxic conditions depends on iNOS modulated ERK phosphorylation in the MDA-MB-231 breast carcinoma cell line.

Urokinase plasminogen activator receptor (uPAR) plays a major role in cancer invasion and metastasis and uPAR expression is correlated with a poor prognosis in various cancer types. Moreover, the expression of uPAR is increased under hypoxic conditions. Nitric oxide (NO) and its metabolites produced by inducible nitric oxide synthase (iNOS) are important products of hypoxic stress, and NO may activate or modulate extracellular signal regulated kinase (ERK). Here, we evaluated uPA, uPAR, and activated ERK levels under hypoxic conditions, and the modulatory effects of iNOS and NO in the MDA-MB-231 human breast cancer cell line. Cells were incubated in a hypoxic or normoxic incubator and treated with PD98059 (a MEK 1/2 inhibitor, which abrogates ERK phosphorylation) and aminoguanidine (a selective iNOS inhibitor). uPAR expression, ERK phosphorylation, and uPA activity were found to be increased under hypoxic conditions. Moreover, when cells were treated with PD98059 under hypoxic conditions, uPAR was downregulated, whereas aminoguanidine markedly increased ERK phosphorylation in a dose dependent manner. Furthermore, aminoguanidine increased uPAR expression and prevented the inhibition of uPAR expression by PD98059. These results demonstrated that uPAR is induced by hypoxia and that increased uPAR expression is mediated by ERK phosphorylation, which in turn is modulated by iNOS/NO in MDA-MB-231 cells. We conclude that iNOS/NO downregulates the expression of uPAR under hypoxic conditions via ERK pathway modulation.

Breast Neoplasms↗
PubMed2006

Treatment outcome of front-line systemic chemotherapy for localized extranodal NK/T cell lymphoma in nasal and upper aerodigestive tract.

We analysed the treatment outcome of localized extranodal NK/T cell lymphoma initially treated with CEOP-B chemotherapy based on the primary site of involvement (nasal cavity vs. upper aerodigestive tract) and treatment modality (chemotherapy vs. chemotherapy followed by radiotherapy. Forty-three patients newly diagnosed as extranodal NK/T cell lymphoma were analysed: 29 cases from nasal cavity/nasopharynx and 14 from upper aerodigestive tract. Twenty-six patients were treated with chemotherapy alone, while adjuvant radiotherapy was given to 17 patients. Overall response rate to front-line CEOP-B chemotherapy was 67.4% (29/43) and the complete remission (CR) rate was 44.2% (19/43). Median overall and disease-free survival was 26.87 months [95% confidence interval (CI) = 8.71 - 45.03] and 15.27 months (95% CI = 2.92 - 27.62). The responders (CR or partial response) to initial CEOP-B chemotherapy showed longer overall survival than non-responders (P = 0.0026). Local relapse was observed to be higher in the chemotherapy alone group compared to the chemoradiotherapy group. Adjuvant radiotherapy failed to improve survival; thus, the median disease-free survival of the chemotherapy and chemoradiotherapy groups was not different (P = 0.9101). There may be a tendency for better overall survival in group of upper aerodigestive tract lymphoma than the nasal cavity/nasopharynx group (P = 0.0643). However, front-line CEOP-B chemotherapy has a limited role and adjuvant radiotherapy failed to improve survival in localized extranodal NK/T cell lymphoma.

Adult↗
PubMed2006

Prospective analysis of treatment outcome and prognostic factors in patients with T-cell lymphomas treated by CEOP-B: single institutional study.

The important prognostic factors were evaluated for T-cell non-Hodgkin lymphoma (NHL) patients in a prospective study using the CEOP-B protocol [a modified cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP)-like regimen that uses epirubicin instead of doxorubicin with the addition of bleomycin]. Fifty-two patients were enrolled in the study. The overall response rate was 63.5%. The median progression-free survival (PFS) and median overall survival (OS) was 18.0 and 39.5 months respectively. The most common toxicity was neutropenia. The factors related to poor outcome were a high International Prognostic Index (IPI) and a high 'B' score (bone marrow involvement, B symptoms, bulky disease). We developed a new prognostic model, namely the Prognostic Group for T cell NHL (PGT) that included four groups: PGT1 (low IPI/low B score), PGT2 (low IPI/high B score), PGT3 (high IPI/Low B score) and PGT4 (high IPI/Low B score). OS and PFS (not reached, 48 months) in the PGT1 group were significantly longer than those (11.5 and 4.8 months) in PGT2. The same result was observed in the PGT3 and PGT4 groups. The CEOP-B regimen was moderately active and tolerable for T-cell NHL patients, and the PGT system might be useful for the prediction of long-term survival of T-cell NHL patients.

Adolescent↗
PubMed2005

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.

ADP-ribosyl Cyclase 1↗
PubMed2005

Phase II study with a combination of epirubicin, cisplatin, UFT, and leucovorin in advanced hepatocellular carcinoma.

PURPOSE: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Because HCC usually presents as an advanced disease and occurs in the background of liver cirrhosis, most patients are not suitable for treatment with curative intent, thus effective systemic chemotherapy is required. However, the outcome of systemic chemotherapy has been disappointing in advanced HCC. This study was conducted to test the efficacy and toxicity of the combined regimen of epirubicin, cisplatin, and UFT moderated by leucovorin in advanced or recurrent HCC. PATIENTS AND METHODS: All 53 patients received epirubicin (50 mg/m2 i.v.) on day 1 and cisplatin (60 mg/m2 i.v.) after epirubicin administration. Oral UFT 400-600 mg/day, determined by body surface area, and leucovorin 75 mg/day were administered for 21 consecutive days, followed by a 7-day drug free interval. RESULTS: Nine had a partial response, representing 16.9% of response rate (95% confidence interval rate; 7.0-26.8%) with median response duration of 17.1 weeks (95% CI; 5.0-29.3 weeks, range; 7.1-51.7 weeks). Fifteen patients had stable disease and the disease progressed in 26 patients. The median overall survival for the patients was 24.6 weeks (95% CI; 17.3-31.9 weeks, range; 3.0-131.3 weeks). The main toxicities were hematologic toxicities including neutropenia, which reached grade 3/4 in 17 patients (38.5%), and grade 3 or 4 thrombocytopenia in five patients (9.4%). CONCLUSION: The combination of epirubicin, cisplatin, and UFT moderated by leucovorin showed modest anti-tumor activity with relatively tolerable toxicities. However, a randomized phase III trial based on this regimen is warranted to clarify its survival benefit in patients with advanced HCC.

Adult↗
PubMed2005

Autocrine vascular endothelial growth factor/vascular endothelial growth factor receptor-2 growth pathway represents a cyclooxygenase-2-independent target for the cyclooxygenase-2 inhibitor NS-398 in colon cancer cells.

OBJECTIVES: Coexpression of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor-2 (VEGFR-2) has been reported in tumor cells, suggesting the presence of an autocrine VEGF/VEGFR-2 growth pathway in solid tumors. Thus, we hypothesize that the presence of this autocrine pathway in colon cancer cells may be a COX-2-independent target of COX-2 inhibitors and a mechanism behind the antitumor effects of these agents. METHODS: COX-2-positive (Caco2, HT-29) and COX-2-negative colon cancer cells (DLD-1, Hct-15) were used. Expression of VEGFR-2 was evaluated by Western blot and reverse transcriptase-polymerase chain reaction and VEGF production was measured from culture supernatant by enzyme-linked immunosorbent assay. Growth inhibition and the expression of VEGF and VEGFR-2 were compared after treatment with the COX-2 inhibitor, NS-398 at doses ranging from 5 to 100 microM. RESULTS: VEGF and VEGFR-2 were expressed in all four colon cancer cells and a blockade of VEGFR-2 with anti-VEGFR-2 antibody treatment induced growth inhibition of colon cancer cells, supporting the presence of autocrine VEGF/VEGFR-2 growth pathway. NS-398 suppressed the growth of colon cancer cells, independent of COX-2 expression. VEGFR-2 expression of tumor cells was reduced after NS-398 treatment at 100 microM, the concentration at which maximal growth inhibition was induced. The amount of VEGF in culture supernatant was increased by NS-398 at 100 microM, suggesting increased secretion of VEGF in compensation for reduced VEGFR-2 expression. CONCLUSION: The autocrine VEGF/VEGFR-2 growth pathway could be a COX-2-independent target of the COX-2 inhibitor, NS-398, in colon cancer cells.

Antineoplastic Agents↗
PubMed2005

Incidence of anemia in older Koreans: community-based cohort study.

Most epidemiologic data are related to the prevalence of anemia, and there is little information regarding the incidence or etiology of newly diagnosed anemia in older people. The purpose of this study was to define the incidence and characteristics of anemia in the elderly population of Korea. Three hundred thirty-two independent, community-living, elderly persons aged 60 years and older were enrolled, and laboratory tests including iron profiles were performed. The mean age was 72+/-4.8 years and the mean hemoglobin was 13.4+/-1.1g/dl. During the follow-up period of 3 years, 24 subjects (3 males and 21 females) were newly diagnosed with anemia, which led to a 3-year incidence of 7.2% (24/332). Among the 24 subjects with new-onset anemia, iron deficiency anemia (IDA) was diagnosed in 5 subjects, while anemia of chronic disease (ACD) was detected in 8 subjects. Underlying illnesses were diabetes mellitus, osteoarthritis, renal insufficiency, hypothyroidism and malignancy. In those subjects with new-onset anemia, the serum iron, ferritin, transferrin saturation and albumin were lower than in the normal group. In conclusion, the 3-year incidence of anemia among Korean elderly people was determined to be 7.2%, and ACD was the most commonly defined cause of anemia.

Age Distribution↗
PubMed2005

Expression of HIF-1alpha, CA IX, VEGF, and MMP-9 in surgically resected non-small cell lung cancer.

Endogenous hypoxia markers have been studied as prognostic indicators because they appear to be associated with tumor aggressiveness. This study was undertaken to compare the expression of two endogenous hypoxia markers, Hypoxia-inducible factor-1alpha (HIF-1alpha) and carbonic anhydrase IX (CA IX), with regard to their prognostic significance. We also compared spatial distribution of HIF-1alpha and CA IX and examined their relationship with expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP)-9, which may be regulated by hypoxia. We studied 74 resected stage I/II non-small cell lung cancers (NSCLCs) for expression of HIF-1alpha, CA IX, VEGF, and MMP-9 by immunohistochemistry, and the extent of tumor necrosis. Univariate and multivariate analyses were performed to assess prognostic implications of these markers for disease free survival. HIF-1alpha expression was strongly correlated with CA IX (r=0.667, p<0.001) and was co-localized with CA IX in corresponding areas. HIF-1alpha and CA IX expression were higher in areas with moderate to severe tumor necrosis relative to areas with minimal necrosis, suggesting their relationship with hypoxia. VEGF expression also showed a modest relationship with HIF-1alpha (p=0.07); however, there was no relationship between HIF-1alpha and MMP-9 expression (p>0.99). Expression of HIF-1alpha and CA IX above the median value was significantly associated with shorter disease free survival in univariate analysis (p<0.05). However, only high CA IX expression and pathologic stage were independent prognostic indicators in a multivariate analysis. Of the markers considered in this study, CA IX expression status was the most reliable hypoxia marker for predicting tumor aggressiveness.

Aged↗
PubMed2004

Carbonic anhydrase IX in early-stage non-small cell lung cancer.

PURPOSE: Tumor hypoxia is associated with poor prognosis and increased tumor aggressiveness. Carbonic anhydrase (CA) IX, an endogenous marker for tumor hypoxia, catalyzes the hydration of carbon dioxide into carbonic acid and contributes to the pH regulation of tumor cells. Therefore, CA IX might allow tumors to acclimate to a hypoxic microenvironment, promoting tumor cell proliferation. We hypothesized that CA IX expression is related to tumor cell proliferation and poor disease-free survival in patients with early-stage non-small-cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: CA IX expression was measured in 75 resected NSCLC tumors to assess prognostic implications for disease-free survival. The relationship of CA IX expression with microvessel density (MVD) and proliferation (Ki-67) index was assessed via colocalization analysis. RESULTS: All patients had operable NSCLC (stage I, 58; stage II, 17). CA IX expression was present in 54 (72%) of 75 patients and was associated with tumor necrosis (P < 0.05). CA IX-positive tumor areas showed greater cell proliferation as measured by Ki-67 index (P < 0.05) and less MVD (P < 0.05) than did CA IX-negative areas in colocalization analysis. The percentage of CA IX-positive tumor cells was significantly related to postoperative recurrence and poor disease-free survival (P < 0.05). Ki-67 index and pathologic stage were also independent prognostic factors for worse disease-free survival (P < 0.05). CONCLUSIONS: CA IX expression of tumor cells may be an indicator for poor disease-free survival in early-stage NSCLC.

Adenocarcinoma↗
PubMed2004

Serum vascular endothelial growth factor per platelet count in hepatocellular carcinoma: correlations with clinical parameters and survival.

BACKGROUND: Platelets have been reported to act as transporters of tumor-originated vascular endothelial growth factor (VEGF), contributing to tumor angiogenesis and progression. Serum VEGF per platelet count, as an indirect theoretical estimate of VEGF in platelets, may predict the malignant potential of tumors. However, its prognostic significance is still unclear in hepatocellular carcinoma (HCC), a highly vascular tumor. METHODS: Serum VEGF was measured by enzyme-linked immunosorbent assay. We compared serum VEGF, platelet count and serum VEGF per platelet count in 52 HCC patients, 26 liver cirrhosis patients and 30 healthy controls. The relation of serum VEGF per platelet count with clinicopathologic variables of HCC patients and the prognostic significance were investigated. RESULTS: Serum VEGF per platelet count in HCC patients was higher than in liver cirrhosis patients and healthy controls (P < 0.01). There was a statistically significant correlation between serum VEGF and platelet count in HCC patients (r = 0.751, P < 0.01). Serum VEGF per platelet count was higher in patients with advanced stage and portal vein thrombosis (P < 0.01). Patients with high serum VEGF per platelet count (>1.4 pg/10(6)) showed poor response to treatment and shorter overall survival (P < 0.01). Serum VEGF per platelet count was an independent prognostic factor with the presence of portal vein thrombosis (P < 0.01). CONCLUSIONS: Serum VEGF per platelet count could be a feasible prognostic indicator during the follow-up of patients with HCC.

Adult↗
PubMed2003

Early lymphopenia as a risk factor for chemotherapy-induced febrile neutropenia.

Febrile neutropenia (FN) is a frequent complication of cancer chemotherapy, which causes death in 4-21% of patients and worsens the quality of life of patients. As a simple and accurate way of identifying patients who are at risk of FN, a lymphocyte count on post-chemotherapy day 5 was suggested. To confirm the feasibility of this method and to define the incidence of FN among our own patient group, we conducted this prospective study. From September 2001 to February 2002, patients who received cytotoxic chemotherapy at Guro Hospital, Korea University, were enrolled. Blood sampling for a complete blood count was done on the starting day of chemotherapy and on day 3 and day 5 post-chemotherapy. The prospective results of the CBC were compared between the FN group and non-FN group. During the study period, 82 patients were enrolled. The male to female ratio was 52:30, and the median age was 56 years old (range: 14-78). Underlying malignancies were non-Hodgkin's lymphoma (14 patients), stomach cancer (17), breast cancer (11), NSCLC (7), hepatobiliary cancer (10), sarcoma (3), colorectal cancer (3), and others (17). The incidence of FN was 18% (15/82 patients), and ANC at the time of FN was 275 +/- 327/ micro l. Duration of fever was 3.9 +/- 3.5 days. The incidence of FN was significantly higher in patients with lymphocyte counts at day 3 < or = 500/micro l (P = 0.06), day 5 < or = 500/micro l (P = 0.023), day 3 < or = 700/micro l (P = 0.01), and day 5 < or = 700/micro l (P = 0.0001). As a result of a logistic regression test, a day-5 lymphocyte count < or = 700/ micro l was identified as an independent risk factor for FN. In conclusion, a day-5 lymphocyte count <700/micro l was a risk factor for FN. To strengthen our result, we are planning to validate in a larger patient group.

Adolescent↗
PubMed2003

Unusual presentation of thymic carcinoma: hypertrophic osteoarthropathy.

Hypertrophic osteoarthropathy is characterized by clubbing and periosteal new bone formation along the shaft of the long bones of the extremities. Although various intrathoracic malignancies have been associated with the development of HOA, it has been extremely rare for HOA to occur in a patient with a thymic carcinoma. Recently, we experienced a 63-year-old woman diagnosed as a thymic carcinoma with hypertrophic osteoarthropathy. She had both digital clubbing and cortical thickening in her lower extremities identified radiologically. We herein describe this case with a review of the literature.

Carcinoma↗
PubMed2003

A case of non-Hodgkin's lymphoma in a patient with neurofibromatosis type 1.

Neurofibromatosis type 1 is characterized by cutaneous neurofibromas and pigmented lesions of the skin called café au lait spots. Although neurofibromatosis type 1 represents a major risk factor for the development of malignancy, especially of nervous system tumors, malignant lymphoma rarely occurs in a patients with neurofibromatosis type 1. Recently, a 77-year-old woman with neurofibromatosis type 1 was diagnosed as non-Hodgkin's Lymphoma (diffuse large B cell). She had multiple café au lait spots, neurofibromas and right axillary lymph node enlargement. An abdominal CT scan demonstrated a left pelvic mass and para-aortic lymphadenopathy. Because non-Hodgkin's Lymphoma in a neurofibromatosis patient has never been reported in Korea, herein, we describe this case and include a review of the literature.

Aged↗
PubMed2002

Hyperlayer separation in hollow fiber flow field-flow fractionation: effect of membrane materials on resolution and selectivity.

Hollow fiber flow FFF (HF FlFFF) has recently shown its capability to separate and characterize the size of submicrometer particles and has demonstrated the potential to be developed into a disposable flow FFF channel. In this work, HF FIFFF was used for the hyperlayer separation of micron-sized particles and the separation capability was examined by using various hollow fiber membrane materials (Polysulfones, cPVC, and PAN). From the experiments, PAN (polyacrylonitriles) showed an outstanding performance in particle separation compared to the other membranes. By orienting the fiber module in an upright direction, the upstream flow migration reduced band broadening of eluted peaks. When the efficiency of the PAN hollow fiber system was tested by varying the ratio of outflow-rate to radial flow-rate, it was found that optimum separation in hyperlayer HF FlFFF can be obtained at the ratio of about 6-7. From the examination of retention at or around steric inversion diameter, it was observed that experiments showed a good agreement with predictions by semi-empirical calculation. In hyperlayer HF FlFFF the diameter based selectivity values were shown to be 1.2-1.7 depending on the type of membranes and the field strength (the radial flow-rate) conditions.

Chemical Fractionation↗