Publications (134)454.17 Total impact
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Article: In vivo tumor targeting and radionuclide imaging with self-assembled nanoparticles: mechanisms, key factors, and their implications.
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ABSTRACT: The development of more selective delivery systems for cancer diagnosis and chemotherapy is one of the most important goals of current anticancer research. The purpose of this study is to evaluate various self-assembled nanoparticles as candidates to shuttle radionuclide and/or drugs into tumors and to investigate the mechanisms underlying the tumor targeting with self-assembled nanoparticles. By combining different hydrophobic moieties and hydrophilic polymer backbones, various self-assembled nanoparticles were prepared, and their in vivo distributions in tumor-bearing mice were studied by radionuclide imaging. One type of nanoparticles (fluorescein isothiocyanate-conjugated glycol chitosan (FGC) nanoparticles) exhibited highly selective tumoral localization. Scintigraphic images obtained 1 day after the intravenous injection of FGC nanoparticles clearly delineated the tumor against adjacent tissues. The mechanisms underlying the tumor targeting with self-assembled nanoparticles were investigated in terms of the physicochemical properties of nanoparticles and tumor microenvironments. FGC nanoparticles were preferentially localized in perivascular regions, implying their extravasation to tumors through the hyperpermeable tumor vasculature. The magnitude and pattern of tumoral distribution of self-assembled nanoparticles were influenced by several key factors--(i) in vivo colloidal stability: nanoparticles should maintain their intact nanostructures in vivo for a long period of time, (ii) particle size, (iii) intracellular uptake of nanoparticle: fast cellular uptake greatly facilitates the tumor targeting, (iv) tumor angiogenesis: pathological angiogenesis permits access of nanoparticles to tumors. We believe that this work can provide insight for the engineering of nanoparticles and be extended to cancer therapy and diagnosis, so as to deliver multiple therapeutic agents and imaging probes at high local concentrations.Biomaterials 03/2007; 28(6):1236-47. · 7.40 Impact Factor -
Article: Clinical utility of 18F-FDG PET for patients with salivary gland malignancies.
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ABSTRACT: The clinical utility of 18F-FDG PET in evaluating salivary gland malignancies has not been well defined. We therefore evaluated the utility of 18F-FDG PET in management for patients with salivary gland cancers. Thirty-four patients with newly diagnosed salivary gland cancers underwent CT and 18F-FDG PET before surgical resection with radiotherapy. The diagnostic accuracies of CT and 18F-FDG PET for detecting primary tumors and neck metastases were compared with a histopathologic reference. We determined the relationship between the maximum standardized uptake value (SUV) of the tumor and clinicopathologic parameters such as sex, age, local tumor invasion, T and N categories, TNM stage, and histologic grade, as well as their associations with disease-free survival (DFS). 18F-FDG PET was more sensitive than CT for the detection of primary tumors (91.2% vs. 79.4%; P < 0.05), cervical metastases (80.5% vs. 56.1%; P < 0.05), and distant metastases in 2 patients at initial staging. High-grade malignancies had higher mean maximum SUVs than did low- and intermediate-grade malignancies (4.6 vs. 2.8; P = 0.011). T and N categories were independent determinants of DFS (P < 0.05), but the maximum SUV (4.0) was not. During a mean follow-up of 25.1 mo, 18F-FDG PET correctly diagnosed local-regional recurrences in 6 patients and new distant metastases in 9 patients. Our findings indicate that, in patients with salivary gland malignancies, 18F-FDG PET is clinically useful in initial staging, histologic grading, and monitoring after treatment but not in predicting patient survival.Journal of Nuclear Medicine 02/2007; 48(2):240-6. · 6.38 Impact Factor -
Article: Antiangiogenic effect of bile acid acylated heparin derivative.
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ABSTRACT: Chemically modified heparin-DOCA was prepared and found to have markedly lower anticoagulant activity than heparin. In the present study, we elucidated the antiangiogenic and antitumoral activities of heparin-DOCA derivative. To evaluate the antiangiogenic and antitumoral effects of heparin-DOCA, capillary-like tube formation assay, Matrigel plug assay in vivo, western blotting for FGFR phosphorylation, ERK and p38 MAPK activities, tumor growth of SCC in vivo and immunostaining of blood vessels in tumor tissues were performed. Heparin-DOCA inhibited capillary-like tubular structures of endothelial cells and bFGF-induced neovascularizations in Matrigel plug assays. Signaling experiments showed that heparin-DOCA significantly inhibited angiogenesis by suppressing the phosphorylation of FGFR and its downstream signal pathways (ERK and p38 MAPK activities). The antiangiogenic activity of this heparin derivative was found to be closely associated with antitumoral activity in a mouse model. In addition, histological evaluations supported the inhibitory effect of heparin-DOCA on blood vessel formation in tumor tissues. Heparin-DOCA derivative exerted a significant antitumoral effect by inhibiting angiogenesis resulting from the disruption of FGF/FGFR and its downstream signal pathways, and could be applied to treat various angiogenic diseases.Pharmaceutical Research 02/2007; 24(1):176-85. · 4.09 Impact Factor -
Article: Anti-tumor and anti-metastatic effects of gelatin-doxorubicin and PEGylated gelatin-doxorubicin nanoparticles in SCC7 bearing mice.
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ABSTRACT: The goal of this study was to develop a systemically non-toxic and stable circulation based passive targeting system for efficient anticancer treatment. Gelatin-doxorubicin (GD) and PEGylated gelatin-doxorubicin (PGD) nanoparticles were designed and their feasibilities as an anti-cancer drug were evaluated. The sizes of GD and PGD nanoparticles were about 135 and 250 nm, respectively, and they retained their structures for 2 days in PBS. Both GD and PGD had much lower cytotoxicity in vitro and in vivo than doxorubicin (DOX) at equivalent concentrations. However, PGD significantly inhibited tumor growth compared to the control and DOX treated group, and GD moderately suppressed tumor growth compared with the control but the suppressing effect of GD did not exceed that of DOX. And GD and PGD both remarkably suppressed pulmonary metastasis. We conclude that PGD is a potential cancer therapeutic, due to its excellent anti-tumor and anti-metastatic effects and low systemic toxicity.Journal of Drug Targeting 01/2007; 14(10):707-16. · 2.70 Impact Factor -
Article: Expression of Ku80 correlates with sensitivities to radiation in cancer cell lines of the head and neck.
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ABSTRACT: The Ku protein is essential for the repair of a majority of DNA double-strand breaks in mammalian cells. The purpose of this study was to investigate the relationship between the expression of Ku70/80 and sensitivity to radiation in cancer cell lines of the head and neck. The sensitivity to radiation in various head and neck cancer cell lines (AMC-HN-1 to -9) was analyzed by colony forming assay. Of the nine cell lines examined, the most radiosensitive cell line (AMC-HN-3) and the most radioresistant cell line (AMC-HN-9) were selected for this experiments. The expression of Ku70/80 was examined after irradiation using real time PCR, Western blotting and immunofluorescence in two different cell lines. Cell cycle distribution after irradiation were analysed. A differential radioresponse was demonstrated by expression of Ku70/80 in AMC-HN-3 and AMC-HN-9 cells. While the expression of Ku70 was slightly increased in the radioresistant AMC-HN-9 cell line, the expression of Ku80 was remarkably increased, suggesting a correlation between Ku80 expression and radiation resistance. Overexpression of Ku80 plays an important role in the repair of DNA damage induced by radiation. Ku80 expression may provide an effective predictive assay of radiosensitivity in head and neck cancers.Oral Oncology 12/2006; 42(10):979-86. · 2.86 Impact Factor -
Article: Association of the GSTP1 and NQO1 polymorphisms and head and neck squamous cell carcinoma risk.
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ABSTRACT: The GSTP1 and NQO1 have been reported to be associated with an increased risk for smoking related head and neck squamous cell carcinoma (HNSCC). The purpose of this study was to determine the effect of these metabolic gene polymorphisms on the risk of HNSCC. The study population included 294 histologically confirmed HNSCC cases and 333 controls without cancer. Genotyping analysis of the GSTP1 Ile105Val and NQO1 Trp139Arg genes was performed by polymerase chain reaction-based techniques on DNA prepared from peripheral blood. The Mantel-Haenszel chi2 test was used for statistical analysis. The allele frequencies of the GSTP1 and NQO1 polymorphisms were not statistically significant between cases and controls. In analyzing the association between smoking amounts and genetic polymorphisms, GSTP1 and NQO1 polymorphisms were associated with cigarette smoking amounts in cases. G allele containing genotypes in GSTP1 and T allele containing genotypes in NQO1 were associated with a tobacco dose-dependent increase in risk of HNSCC and these genotype distributions were statistically significant (p<0.05). We found that the GSTP1 105Val allele and NQO1 139Arg allele were associated with tobacco dose-dependent increase in risk of HNSCC. GSTP1 and NQO1 genotype polymorphisms may play an important role in the development of smoking related HNSCC.Journal of Korean Medical Science 12/2006; 21(6):1075-9. · 0.99 Impact Factor -
Article: The BRAF mutation is useful for prediction of clinical recurrence in low-risk patients with conventional papillary thyroid carcinoma.
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ABSTRACT: The activating BRAF(V600E) mutation is the most common genetic alteration reported in papillary thyroid carcinoma (PTC). While some reports suggest the BRAF(V600E) mutation is associated with factors predicting a poor prognosis and recurrence, this remains a controversial issue. To determine whether the presence of the BRAF(V600E) mutation is a prognostic indicator for clinical recurrence in low-risk patients with conventional PTC. The study involved 203 conventional PTC patients who underwent total or near-total thyroidectomy followed by immediate 131I ablation of the remnants. Patients with antithyroglobulin antibodies and those with extracervical metastases at presentation were excluded. DNA was extracted from paraffin-embedded tumour specimens, and the presence of the BRAF(V600E) mutation was evaluated using PCR amplification and direct sequencing. The BRAF(V600E) mutation was found to be present in 149 (73.4%) of 203 patients. The BRAF(V600E) mutation was correlated with male gender (P = 0.006) and with tumour size (P = 0.005). While there appeared to be an association between the BRAF(V600E) mutation and extrathyroid extension, this did not reach statistical significance (P = 0.062). During follow-up of the 203 patients (median 7.3 years; range 0.7-10.0 years), 36 (18%) patients experienced recurrence. While univariate analysis showed the BRAF(V600E) mutation was associated with tumour recurrence (21% with mutation vs 7% without mutation; P = 0.037), this association was not shown following multivariate analyses adjusting for the clinicopathological prognostic factors of age, gender, tumour size, extrathyroid extension, multifocality and lymph node metastasis. Although the BRAF(V600E) mutation was found to be associated with a higher clinical recurrence of disease in low-risk conventional PTC patients, it was not an independent predictor.Clinical Endocrinology 10/2006; 65(3):364-8. · 3.17 Impact Factor -
Article: N-acetyl histidine-conjugated glycol chitosan self-assembled nanoparticles for intracytoplasmic delivery of drugs: endocytosis, exocytosis and drug release.
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ABSTRACT: Nano-sized vesicular systems (nanoparticles), ranging from 10 nm to 1000 nm in size, have potential applications as drug delivery systems. Successful clinical applications require the efficient intracellular delivery of drug-loaded nanoparticles. Here we describe N-acetyl histidine-conjugated glycol chitosan (NAcHis-GC) self-assembled nanoparticles as a promising system for intracytoplasmic delivery of drugs. Because N-acetyl histidine (NAcHis) is hydrophobic at neutral pH, the conjugates formed self-assembled nanoparticles with mean diameters of 150-250 nm. In slightly acidic environments, such as those in endosomes, the nanoparticles were disassembled due to breakdown of the hydrophilic/hydrophobic balance by the protonation of the imidazole group of NAcHis. Cellular internalization and drug release of the pH-sensitive self-assembled nanoparticles were investigated by flow cytometry and confocal microscopy. NAcHis-GC nanoparticles internalized by adsorptive endocytosis were exocytosed or localized in endosomes. The amount of exocytosed nanoparticles was dependent on the pre-incubation time prior to removal of free nanoparticles from the culture media. Flow cytometry and confocal microscopy showed that NAcHis-GC nanoparticles released drugs into the cytosol and cell cycle analysis demonstrated that paclitaxel-incorporated NAcHis-GC nanoparticles were effective in inducing arrest of cell growth.Journal of Controlled Release 10/2006; 115(1):37-45. · 5.73 Impact Factor -
Article: Heparin-deoxycholic acid chemical conjugate as an anticancer drug carrier and its antitumor activity.
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ABSTRACT: A chemically modified heparin-DOCA (HD) conjugate was developed as a drug carrier for cancer therapy. HD conjugate was found to have markedly low anticoagulant activity and to form self-assembled nanoparticles in aqueous condition. We observed that HD conjugate prevented squamous cell carcinoma (SCC) and human umbilical vascular endothelial cell (HUVEC) proliferation during BrdU incorporation assays. Here, we prepared doxorubicin-loaded heparin nanoparticles by entrapping doxorubicin into the amphiphilic HD conjugate by physical interaction and characterized the properties of these nanoparticles using Dynamic Light Scattering (DLS) and Atomic Force Microscope (AFM). In this study, doxorubicin-loaded heparin nanoparticles were designed to improve the antitumor effects of nano-sized particles (range of 180 to 210 nm) at high drug-loading efficiencies in the range 64% to 96%. These doxorubicin-loaded heparin nanoparticles displayed sustained drug release patterns. It was confirmed in vivo toxicity studies that HD conjugate did not induce unexpected side effects and that DHN 20 was safer than free DOX. An in vivo study showed that HD conjugate, doxorubicin and DHN 20 (one of doxorubicin-loaded heparin nanoparticles) induced tumor volume reductions of 43%, 56% and 74%, respectively, relative to the saline treated control. These results suggest that the drug-entrapped with heparin nanoparticles might provide a novel therapy for SCC.Journal of Controlled Release 10/2006; 114(3):300-6. · 5.73 Impact Factor -
Article: Chemopreventive efficacy of all-trans-retinoic acid in biodegradable microspheres against epithelial cancers: results in a 4-nitroquinoline 1-oxide-induced oral carcinogenesis model.
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ABSTRACT: Retinoids are known to suppress carcinogenesis in various epithelial tissues. Among them, all-trans-retinoic acid (atRA) is recognized as one such active retinoid. However, despite the known anticarcinogenic activity of atRA, it exhibits its short plasma half-life during repeated oral administration due to the "acute retinoid resistance" in the liver. This has been the major limitation in clinical applications of atRA. Therefore, in order to render atRA more suitable for clinical uses, sustained delivery of atRA using biodegradable microspheres is suggested in this study. When 50 mg atRA/kg of atRA-loaded microspheres were subcutaneously administered to rats once, the atRA concentration in plasma was maintained around 6.5 ng/ml for 7 weeks, with only minor signs of toxicity. When the chemopreventive efficacy of atRA-loaded microspheres was evaluated using a model of 4-nitroquinoline 1-oxide-induced oral carcinogenesis in F344 rats, a single injection of atRA-loaded microspheres significantly suppressed oral carcinogenesis. Additional injections of atRA-loaded microspheres, however, did not indicate further suppression of carcinogenesis.International Journal of Pharmaceutics 09/2006; 320(1-2):45-52. · 3.35 Impact Factor -
Article: Clinical significance of beta1 integrin expression as a prediction marker for radiotherapy in early glottic carcinoma.
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ABSTRACT: To determine the significance of beta1 integrin expression as a prediction marker for the response to radiotherapy in patients with early glottic carcinoma. Retrospective study in a tertiary referral center. Among the T1/T2 glottic carcinoma patients treated with radiotherapy from 1992 to 2002, 52 had more than 2 years of follow-up and available pretreatment biopsy specimens. The immunohistochemical staining was performed for the assay of beta1 integrin expression, and the staining pattern of each was classified as diffuse, localized, or negative. The associations between the patterns of beta1 integrin expression and clinicopathologic parameters, including response to radiotherapy, involvement of the anterior commissure, and grade of histologic differentiation, were evaluated. After radiotherapy, 42 patients remained tumor free, and 10 patients had recurrent or persistent disease. Six (12%) specimens were negative for beta1 integrin expression, 39 (75%) had a localized staining pattern, and 7 (13%) had a diffuse staining pattern. Recurrence rate was significantly higher in the diffuse group (53%) than in the localized (13%) or negative (17%) groups (P=.023). The pattern of beta1 integrin expression was also closely related to histologic differentiation (P=.008), although the association between response to radiotherapy and histologic differentiation was not significant The pattern of expression of beta1 integrin, which has been known as a stem cell marker of the epidermis, may be helpful in predicting the response to radiation in patients with early glottic carcinoma.The Laryngoscope 08/2006; 116(7):1228-31. · 1.75 Impact Factor -
Article: Preliminary results of a phase I/II study of simultaneous modulated accelerated radiotherapy for nondisseminated nasopharyngeal carcinoma.
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ABSTRACT: To present preliminary results of intensity-modulated radiotherapy (IMRT) with the simultaneous modulated accelerated radiotherapy (SMART) boost technique in patients with nasopharyngeal carcinoma (NPC). Twenty patients who underwent IMRT for nondisseminated NPC at the Asan Medical Center between September 2001 and December 2003 were prospectively evaluated. Intensity-modulated radiotherapy was delivered with the "step and shoot" SMART technique at prescribed doses of 72 Gy (2.4 Gy/day) to the gross tumor volume, 60 Gy (2 Gy/day) to the clinical target volume and metastatic nodal station, and 46 Gy (2 Gy/day) to the clinically negative neck region. Eighteen patients also received cisplatin once per week. The median follow-up period was 27 months. Nineteen patients completed the treatment without interruption; the remaining patient interrupted treatment for 2 weeks owing to severe pharyngitis and malnutrition. Five patients (25%) had Radiation Therapy Oncology Group Grade 3 mucositis, whereas 9 (45%) had Grade 3 pharyngitis. Seven patients (35%) lost more than 10% of their pretreatment weight, whereas 11 (55%) required intravenous fluids and/or tube feeding. There was no Grade 3 or 4 xerostomia. All patients showed complete response. Two patients had distant metastases and locoregional recurrence, respectively. Intensity-modulated radiotherapy with the SMART boost technique allows parotid sparing, as shown clinically and by dosimetry, and might also be more effective biologically. A larger population of patients and a longer follow-up period are needed to evaluate ultimate tumor control and late toxicity.International Journal of Radiation OncologyBiologyPhysics 06/2006; 65(1):152-60. · 4.11 Impact Factor -
Article: Sarcomatoid salivary duct carcinoma of the larynx.
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ABSTRACT: The sarcomatoid variant is a rare subtype of salivary duct carcinoma that comprises epithelial and sarcomatoid components. The authors present the first reported case of sarcomatoid salivary duct carcinoma occurring in the larynx, which was successfully treated by partial laryngectomy with ipsilateral neck dissection, with no evidence of recurrence after five years. Microscopic analysis revealed a composite epithelial and sarcomatoid tumour. The epithelial component was characterized by papillary proliferation of glandular and ductal structures lined with multilayered epithelial tumour cells. The sarcomatoid component was characterized by pleomorphic spindle cells with cytologic atypia, accompanied by small lymphoid cells, extensive proliferation of blood vessels and focal myxoid changes. To the best of our knowledge, only one case of sarcomatoid salivary duct carcinoma outside a major salivary gland has been reported previously in the literature, and this is the first report of sarcomatoid salivary duct carcinoma arising from the larynx.The Journal of Laryngology & Otology 03/2006; 120(2):154-7. · 0.60 Impact Factor -
Article: Size control of self-assembled nanoparticles by an emulsion/solvent evaporation method
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ABSTRACT: A novel and simple method for size control of self-assembled nanoparticles is suggested in this paper. Polymeric nanoparticles were prepared from amphiphilic chitosan derivatives fluorescein isothiocyanate (FITC)-conjugated glycol chitosans (FGCs). The attachment of hydrophobic FITC onto hydrophilic glycol chitosan induced the amphiphilic conjugate to form self-assembled nanoparticles in aqueous media, depending on degree of substitution. The size of self-assembled nanoparticles was controlled by a novel emulsion/solvent evaporation method. Adding a small amount of an immiscible solvent with water (chloroform) to FGC nanoparticle suspensions in aqueous media followed by ultrasonification and solvent evaporation led to partial dissociation and subsequent reformation of nanoparticles. The evaporation of chloroform facilitated the hydrophobic association, which resulted in more dense and hardened hydrophobic cores. The size of nanoparticles was closely related with the FGC concentration in the emulsion. The mean diameters of self-assembled nanoparticles were 150–500nm at the FGC concentrations of 0.3–2.5mg/ml. Higher FGC concentration resulted in larger particles. The polydispersity factors (μ 2/Γ 2) of the reformed nanoparticles were fairly low (0.001–0.094), indicating narrow size distribution. The FGC nanoparticles were stable in phosphate-buffered saline at 37°C up to 20days. Lactose was a good excipient for maintaining the structural integrity of nanoparticles during freeze-drying. Without lactose, the freeze-dried nanoparticles were not homogeneously redispersed in aqueous media. However, the freeze-dried nanoparticles with lactose were spontaneously redispersed in aqueous milieu with their own sizes.Colloid and Polymer Science 01/2006; 284(5):506-512. · 2.33 Impact Factor -
Article: The polymorphism and haplotypes of XRCC1 and survival of non-small-cell lung cancer after radiotherapy.
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ABSTRACT: The X-ray repair cross-complementing Group 1 (XRCC1) protein is involved mainly in the base excision repair of the DNA repair process. This study examined the association of 3 polymorphisms (codon 194, 280, and 399) of XRCC1 and lung cancer in terms of whether or not these polymorphisms have an effect on the survival of lung cancer patients who have received radiotherapy. Between January 2000 and April 2004, 229 lung cancer patients with non-small-cell lung cancer in Stages I-III were enrolled. Genotyping was performed by single base primer extension assay using the SNP-IT Kit with genomic DNA samples from all patients. The haplotype of the XRCC1 polymorphisms was estimated by PHASE version 2.1. The patients consisted of 191 (83.4%) males and 38 (16.6%) females with a median age of 62 (range, 26-88 years). Sixty percent of the patients were included in Stage I-IIIa. The median progression-free and overall survival was 13 months and 16 months, respectively. The XRCC1 codon 194, histology, and stage were shown to be significant predictors of the progression-free survival. The 6 haplotypes among the XRCC1 polymorphisms (194, 280, and 399) were estimated by PHASE v.2.1. The patients with haplotype pairs other than the homozygous TGG haplotype pairs survived significantly longer (p = 0.04). Polymorphisms of XRCC1 have an effect on the survival of lung cancer patients treated with radiotherapy, and this effect seems to be more significant after the haplotype pairs are considered.International Journal of Radiation OncologyBiologyPhysics 12/2005; 63(3):885-91. · 4.11 Impact Factor -
Article: The BRAF mutation is not associated with poor prognostic factors in Korean patients with conventional papillary thyroid microcarcinoma.
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ABSTRACT: The BRAF(V600E) mutation, the most common genetic alteration reported in papillary thyroid carcinoma, has been associated with poor prognostic factors. To determine whether the presence of the BRAF(V600E) mutation is associated with poor prognosis in Korean patients with conventional papillary thyroid microcarcinoma (micro-PTC). DNA was extracted from paraffin-embedded thyroid tumour specimens taken from 60 patients with conventional micro-PTC, as well as from nine patients with follicular variant papillary carcinoma, six with nodular hyperplasia, four with follicular carcinoma (including one with Hürthle cell carcinoma), four with follicular adenoma (including two with Hürthle cell adenoma) and one each with medullary carcinoma, poorly differentiated carcinoma and anaplastic carcinoma. The presence of the BRAF(V600E) mutation was determined by polymerase chain reaction (PCR) amplification of exon 15 followed by direct sequencing. The BRAF(V600E) mutation was detected in tumour samples from 31 of 60 conventional micro-PTC patients (52%), but was not detected in patients with other types of thyroid tumours. The age distribution, tumour size, extrathyroid extension, multifocality and staging did not differ significantly between patients with and without the BRAF(V600E) mutation. In Korean patients with conventional micro-PTC, the presence of the BRAF(V600E) mutation was not significantly associated with prognostic factors.Clinical Endocrinology 12/2005; 63(5):588-93. · 3.17 Impact Factor -
Article: Expressions of Ku70 and DNA-PKcs as prognostic indicators of local control in nasopharyngeal carcinoma.
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ABSTRACT: The objective of this study was to determine whether the expressions of the two components of DNA-dependent protein kinase, Ku70 and DNA-protein kinase catalytic subunit (DNA-PKcs), influence the response to radiotherapy (RT) and outcome of treatment of nondisseminated nasopharyngeal carcinoma (NPC) in patients who received definitive RT. Sixty-six patients with NPC who were treated with radiotherapy alone or with concurrent chemotherapy between June 1995 and December 2001 were divided into groups based on the levels of immunoreactivity for Ku70 and DNA-PKcs in pretreatment biopsy specimens. The overexpression of Ku70 or DNA-PKcs groups included patients whose biopsy specimens showed at least 50% immunopositive tumor cells; patients in which less than 50% of the tumor cells in the biopsy tissues were immunopositive were placed in the low Ku70 and DNA-PKcs groups. The immunoreactivities for Ku70 and DNA-PKcs were retrospectively compared with the sensitivity of the tumor to radiation and the patterns of therapy failure. Univariate analyses were performed to determine the prognostic factors that influenced locoregional control of NPC. The 5-year locoregional control rate was significantly higher in the low Ku70 group (Ku-) (85%) than in the high Ku70 group (Ku+) (42%) (p = 0.0042). However, there were no differences in the metastases-free survival rates between the 2 groups (Ku70+, 82%; Ku70- 78%; p = 0.8672). Univariate analysis indicated that the overexpression of Ku70 surpassed other well-known predictive clinicopathologic parameters as an independent prognostic factor for locoregional control. Eighteen of 22 patients who had locoregional recurrences of the tumor displayed an overexpression of Ku70. No significant association was found between the level of DNA-PKcs expression and the clinical outcome. Our data suggest that the level of Ku70 expression can be used as a molecular marker to predict the response to RT and the locoregional control after RT and concurrent chemotherapy in patients with nondisseminated NPC.International Journal of Radiation OncologyBiologyPhysics 09/2005; 62(5):1451-7. · 4.11 Impact Factor -
Article: Chemoprevention of 4-NQO-induced oral carcinogenesis by co-administration of all-trans retinoic acid loaded microspheres and celecoxib.
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ABSTRACT: All-trans retinoic acid (atRA) is one of the most potential chemopreventive agents for head and neck squamous cell carcinoma (HNSCC). However, the induced metabolism of atRA by cytochrome P450s in the liver limits its clinical applications. To overcome such limitation, we had developed atRA-loaded microspheres designed to release atRA for a long period. Unfortunately, the atRA-loaded microspheres severely induced inflammatory responses: that is, atRA released from the microspheres significantly induced the proliferation of fibroblasts and collagen deposition, thereby causing a permeability barrier for drugs from entering the blood stream. In the present study, the effects of celecoxib as an anti-inflammatory drug are investigated when it is concurrently used with atRA-loaded microspheres to treat 4-NQO-induced oral carcinogenesis. We investigated if it might influence the plasma concentration of atRA and its metabolism by preventing the fibroblast proliferation and collagen deposition, reduce the toxicity level of atRA, and improve the chemopreventive efficacy of atRA-loaded microspheres. The concurrently administered celecoxib prevented inflammatory responses and suppressed the number of fibroblasts and collagen deposition in the fibrous capsules for 14 days. The atRA concentration in plasma was also increased and the metabolism of atRA was significantly decreased within 2 weeks. In the 4-NQO-induced oral carcinogenesis study, the incidence of invasive SCC was above 44% when F344 rats were treated with atRA-loaded microspheres. However, the treatment using atRA-loaded microspheres and celecoxib concurrently could reduce the incidence of invasive SCC up to 28%, and three of 25 rats were found to have no tongue lesions. In conclusion, the concurrent use of celecoxib could maintain the atRA concentration in plasma at a higher level while reducing its metabolism by preventing inflammatory responses, thereby improving their chemopreventive effects against 4-NQO-induced oral carcinogenesis.Journal of Controlled Release 06/2005; 104(1):167-79. · 5.73 Impact Factor -
Article: Early evaluation of the response to radiotherapy of patients with squamous cell carcinoma of the head and neck using 18FDG-PET.
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ABSTRACT: The aim was to evaluate the efficacy of positron emission tomography (PET) with 2-[F-18]fluoro-2-deoxy-d-glucose (FDG) in early discrimination of response to definitive radiotherapy (RT) in patients with squamous cell carcinoma of the head and neck (SCCHN). Twenty-four patients who underwent FDG-PET scans before and after radiotherapy for nondisseminated SCCHN at the Asan Medical Center between August 2001 and September 2002 were prospectively evaluated. Initial FDG-PET scans were performed within 1 month before RT, and follow-up FDG-PET scans were performed 1 month after completion of RT. FDG-PET images were analyzed by standard uptake value (SUV). All patients were followed for more than 6 months. Pretreatment SUV ranged from 3.4 to 14.0 (median, 6.0), while posttreatment SUV ranged from ground level to 7.7 (median, 2.0). In evaluating residual tumors in these SCCHN patients, the overall sensitivity of FDG-PET was 100%, while its overall specificity was 87%. FDG-PET is effective in evaluating the response to radiation in patients with SCCHN. Timing the follow-up FDG-PET scan 1 month after completion of RT was not too rapid for evaluating the response to radiation.Oral Oncology 05/2005; 41(4):390-5. · 2.86 Impact Factor -
Article: Radiation therapy with UFT and low dose weekly cisplatin for nasopharyngeal carcinoma.
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ABSTRACT: We conducted this study to determine the effectiveness and toxicity of chemoradiation therapy using UFT and low-dose cisplatin in 37 patients with nasopharyngeal carcinoma (NPC). Between March 1999 and December 2001, 37 patients with newly diagnosed and histologically proven nasopharyngeal carcinoma treated in Department of Radiation Oncology, Asan Medical Center were enrolled in this protocol. Cisplatin was administered weekly, starting on day 1 of radiation therapy, as an intravenous infusion at 20 mg/m2 of body-surface area. Oral UFT was administered daily, at a dose of 300 mg in three divided doses. Radiation therapy was given in doses of 1.8-2.0 Gy, 5 days per week, with 4-15 MV photons. The dose of elective nodal area was 60 Gy, and primary tumors and enlarged lymph nodes were boosted with intracavitary brachytherapy or 3D conformal therapy. All patients received the planned doses of radiation. Cisplatin was administered for a median of 6 cycles, and 81% of patients received UFT for more than 5 weeks. The complete response rate was 95% for all patients, and the overall response rate was 100%. No patient experienced hematologic toxicity of grade 3 or higher. Five patients experienced grade 3 non-hematologic toxicity but recovered with conservative management. There was no treatment-related hospitalization or death. These findings suggest that UFT and low-dose cisplatin is a safe and effective regimen of concurrent chemoradiation therapy for patients with nasopharyngeal carcinoma.Auris Nasus Larynx 04/2005; 32(1):43-8. · 0.76 Impact Factor
Top co-authors
Top Journals
Institutions
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2002–2013
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Ulsan University Hospital
Ulsan, Ulsan, South Korea
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2012
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Sungkyunkwan University
Seoul, Seoul, South Korea -
CHA University
Seoul, Seoul, South Korea
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2007–2012
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Seoul National University
- College of Pharmacy
Seoul, Seoul, South Korea -
Hanyang University
- Division of Chemical Engineering and Bioengineering
Ansan, Gyeonggi, South Korea
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2011
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Hallym University Medical Center
Seoul, Seoul, South Korea -
Pusan National University
Pusan, Busan, South Korea
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2007–2010
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Korea Institute of Science and Technology
Seoul, Seoul, South Korea
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2009
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Gyeongsang National University
- Department of Otolaryngology
Chinju, South Gyeongsang, South Korea
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2002–2009
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Asan Medical Center
Seoul, Seoul, South Korea
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2002–2008
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University of Ulsan
- • Department of Radiation Oncology
- • Asan Medical Center
Ulsan, Ulsan, South Korea
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2002–2007
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Gwangju Institute of Science and Technology
- Department of Materials Science and Engineering
Kwangju, Gwangju, South Korea
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2006
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Kyung Hee University
Seoul, Seoul, South Korea
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2004
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National Cancer Center Korea
Seoul, Seoul, South Korea
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