Biomedical subjects

Sang Yoon Kim

Publications and source records attributed to Sang Yoon Kim.

30 records · Page 2Linked to original sources

PubMed2005

Hypoxia activates the cyclin D1 promoter via the Jak2/STAT5b pathway in breast cancer cells.

Hypoxia, a common consequence of solid tumor growth in breast cancer or other cancers, serves to propagate a cascade of molecular pathways which include angiogenesis, glycolysis, and various cell-cycle control proteins. As we have shown previously, hypoxia activates STAT5 (signal transducer and activator of transcription 5) and increases its binding activity to the GAS element in mammary epithelial cells. In this study we attempted to elucidate the mechanism by which cyclin D1 is regulated by the STAT5 protein under hypoxic conditions. Our data demonstrate that hypoxia (2% O(2)) or desferrioxamine (DFO) induces tyrosine and serine phosphorylation of STAT5 in human breast cancer cells (MCF-7) and mammary epithelial cells (HC11). Imunoprecipitation and subsequent Western analysis showed that Jak2 leads to the tyrosine phosphorylation and activation of STAT5a or STAT5b under hypoxic conditions. Using a transfected COS-7 cell model system, we demonstrate that the activity of a cyclin D1 promoter-luciferase construct increased under hypoxic conditions or DFO treatment. The activity of the STAT5b/cyclin D1 promoter increased significantly by 12 h of hypoxia, whereas the activity of the STAT5a/cyclin D1 promoter was unaffected under hypoxic conditions. These increases in promoter activity are predominantly mediated by the Jak2/STAT5b signaling pathway. We have shown by EMSA that hypoxia induces STAT5 to bind to the cyclin D1 promoter (GAS-1) in MCF-7 and HC11 cells. These data suggest that STAT5b may mediate the transcriptional activation of cyclin D1 after hypoxic stimulation.

Anaerobiosis↗

PubMed2005

Expressions of Ku70 and DNA-PKcs as prognostic indicators of local control in nasopharyngeal carcinoma.

PURPOSE: 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. METHODS AND MATERIALS: 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. RESULTS: 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. CONCLUSIONS: 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.

Adult↗

PubMed2005

Chemoprevention of 4-NQO-induced oral carcinogenesis by co-administration of all-trans retinoic acid loaded microspheres and celecoxib.

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.

4-Nitroquinoline-1-oxide↗

PubMed2005

Early evaluation of the response to radiotherapy of patients with squamous cell carcinoma of the head and neck using 18FDG-PET.

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.

Adolescent↗

PubMed2005

The BRAF mutation is not associated with poor prognostic factors in Korean patients with conventional papillary thyroid microcarcinoma.

BACKGROUND: The BRAF(V600E) mutation, the most common genetic alteration reported in papillary thyroid carcinoma, has been associated with poor prognostic factors. AIM: 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). PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSION: In Korean patients with conventional micro-PTC, the presence of the BRAF(V600E) mutation was not significantly associated with prognostic factors.

Adenoma↗

PubMed2004

Radiation therapy with UFT and low dose weekly cisplatin for nasopharyngeal carcinoma.

OBJECTIVE: 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). PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSION: These findings suggest that UFT and low-dose cisplatin is a safe and effective regimen of concurrent chemoradiation therapy for patients with nasopharyngeal carcinoma.

Adult↗

PubMed2004

The effect of cellular retinoic acid binding protein-I expression on the CYP26-mediated catabolism of all-trans retinoic acid and cell proliferation in head and neck squamous cell carcinoma.

The aim of this study was to confirm if catabolism of all-trans retinoic acid (RA) is enhanced by type I cellular retinoic acid binding protein (CRABP-I) expression and to investigate the effect of this enhanced catabolism on cell proliferation of the head and neck squamous cell carcinoma (HNSCC) cell line, AMC-HN-7. We also analyzed the effects of CRABP-I on RA-induced retinoic acid receptor (RAR) activity. The expression of the CRABP-I in stably transfected AMC-HN-7 cell lines (HN7-BPIa and HN7-BPIb) resulted in a lower sensitivity to administered RA compared with that of controls in a clonogenic assay. HN7-BPIs cells showed an increased amount of polar metabolites of RA in thin-layer chromatography. The transcriptional activity of the reporter plasmid RARE(DR5)-tk-CAT after the treatment of RA was lesser in HN7-BPIs than in controls. These results suggest that the increased CYP26-mediated catabolism of RA by CRABP-I transfection might decrease the amount of RA that is accessible to the nuclear receptors and make HNSCC cells resistant to RA.

Blotting, Western↗

PubMed2003

Inhibition of tumor growth by biodegradable microspheres containing all-trans-retinoic acid in a human head-and-neck cancer xenograft.

Retinoids play essential roles in the regulation of cell differentiation and in the proliferation of various epithelial tissues, and atRA is one such active metabolite of retinoids. However, despite the known functions of atRA, its clinical applications are limited due to the induced metabolism by the specific cytochrome P-450s in the liver. To overcome the limitation, parenteral administration of atRA-loaded biodegradable microspheres, the PDLLA/PLE microspheres containing atRA, was suggested previously. We evaluated chemotherapeutic efficacy of atRA-loaded microspheres in a human head-and-neck xenograft/nude mouse model. When atRA-loaded microspheres were administered s.c. at 200 mg/kg body weight to athymic nude mice, plasma concentration of atRA could be maintained in a range of 1.2 to 3.7 x 10(-8) M for 4 weeks. As a result, the tumor volume of human head-and-neck cancer was reduced compared to the control group by 51.3% (p < 0.01) at 14 days and by 49.2% (p < 0.05) at 28 days.

Animals↗

PubMed2002

Analysis of voice and quantitative measurement of glottal gap after thyroplasty type I in the treatment of unilateral vocal paralysis.

Thyroplasty type I is one of several surgical treatments in which improving the voice of unilateral vocal fold paralysis is the ultimate objective. The goal of the surgery is the medialization of the paralyzed vocal fold. The purpose of this study is to evaluate the effectiveness of thyroplasty type I through acoustical analysis, aerodynamic measures, and quantitative videostroboscopic measurements. We report on 20 patients with unilateral vocal cord paralysis who underwent thyroplasty type I. We performed preoperative and postoperative video image analysis (normalized glottal gap area) and computer-assisted voice analysis (fundamental frequency, jitter, shimmer, noise-to-harmonic ratio, mean phonation time, mean flow rate, mean subglottic pressure) in all patients. The glottal gap was significantly reduced after thyroplasty type I. Postoperative voice quality was characterized by an improved pitch and amplitude pertubation (jitter and shimmer), phonation time (mean phonation time), and subglottic pressure (mean subglottic pressure). Thyroplasty type I is an effective method for regaining glottal closure and vocal function.

Adult↗

PubMed2002

Retinoic acid 4-hydroxylase-mediated catabolism of all-trans retinoic acid and the cell proliferation in head and neck squamous cell carcinoma.

All-trans retinoic acid (RA) can be catabolized to polar metabolites by microsomal P450s (P450). The aim of this study was to confirm if retinoic acid 4-hydroxylase (CYP26) is a P450 induced by RA and to investigate the role of cellular RA binding proteins (CRABPs), using a slow catabolizer, AMC-HN-4, and a rapid catabolizer, AMC-HN-6. Also, we analyzed the effect of RA catabolism on cell proliferation of head and neck squamous cell carcinoma (HNSCC) in vitro and in vivo. Both cell lines weakly expressed CYP26 and CRABPs, but RA induced CYP26 only in AMC-HN-6. The sensitivity to RA was variable by the amount of CYP26, and the rapid catabolism by CYP26 made AMC-HN-6 resistant to RA in vitro. In addition, The RA had a stronger effect on the inhibition of tumor growth of AMC-HN-4 than that of AMC-HN-6 in vivo. Conclusively, the CYP26 activity might be one essential factor for the RA sensitivity, but in cells showing induction of CYP26, the RA sensitivity is inversely related to the rate of RA catabolism.

Animals↗

PubMed2002

In vivo biocompatibility studies of poly(D,L-lactide)/poly(ethylene glycol)-poly(L-lactide) microspheres containing all-trans-retinoic acid.

Biocompatibility studies of all-trans-retinoic acid (RA)-loaded microspheres were carried out after they were subcutaneously injected into rats. To characterize the inflammatory response to these microspheres, tissue reactions at the implantation site and cell types in the interstices of the microspheres were evaluated for 180 days. On the 15th day, the cross-sectional area of the fibrous capsules surrounding the implantation site of the RA-loaded microspheres was four times larger than that of the control microspheres. The size of the fibrous capsules surrounding the implantation site of the RA-loaded microspheres decreased significantly over a period of 75 days, while the size of the fibrous capsules surrounding the implantation site of the control microspheres remained almost constant throughout the entire course of 180 days. The tissue response to the RA-loaded microspheres was more intensified by the increased extensive cellular infiltration of macrophages, granulation tissue, and fibrosis than that to the control microspheres. The difference in the inflammatory response between the RA-loaded microspheres and the control microspheres was significant for 75 days after implantation. It was suggested that the released RA from the microspheres stimulated inflammatory responses. However, no further enhanced inflammation reactions were detected after RA had been completely released from the microspheres.

Animals↗

PubMed2002

Solitary fibrous tumor of the parapharyngeal space: MR imaging findings.

We report the MR imaging findings of a solitary fibrous tumor involving the parapharyngeal space. The tumor was a well-circumscribed solid mass with a lobulated contour. It had the same signal intensity as the muscle on T1-weighted MR images, heterogeneously high signal intensity on T2-weighted images, and homogeneous strong enhancement after the administration of contrast material. It mimicked a tumor originating from the deep lobe of the parotid gland.

Diagnosis, Differential↗