Biomedical subjects

Se-Heon Kim

Publications and source records attributed to Se-Heon Kim.

11 recordsLinked to original sources

PubMed2007

HPV integration begins in the tonsillar crypt and leads to the alteration of p16, EGFR and c-myc during tumor formation.

The prevalence of human papillomavirus (HPV) infection is high in the oropharyngeal mucosal regions, of which the tonsil is the most commonly affected. There may be a link between HPV and the pathogenesis of tonsillar cancer (TC), because of common anatomical characteristics between cervical and tonsillar cancer. We aimed to clarify whether HPV directly affects the oncogenesis and biologic behavior of TC by making a comparison between infection prevalence, physical status and viral loading numbers, and clinicopathologic prognostic factors. To compare HPV-related molecules between TC and tonsillitis (CFT), p16, survivin, HIF-1alpha, skp-1, cyclin A, cyclin B1, c-myc and EGFR were investigated. We observed a significant difference in HPV prevalence between 52 TCs and 69 CFTs (73.1% vs. 11.6%), and most of the HPVs were type 16 (87.2%) and nonepisomal (94.1%). Most TCs associated with HPV arose from the tonsillar crypts, and tended to be inverted and poorly differentiated. Compared with HPV-negative TC, HPV-positive TC showed a strong association with p16 overexpression (p<0.0001), and an inverse association with EGFR amplification (p=0.0478). HPV-16 integration status was strongly associated with c-myc amplification (p=0.034) and HIF-1alpha overexpression (p=0.022). HPV-16 integration could be directly related to tonsillar carcinogenesis initially in tonsillar crypts, followed by cell cycle aberration such as p16 overexpression related to the G1-S phase.

Carcinoma, Squamous Cell↗

PubMed2006

Correlations of oral tongue cancer invasion with matrix metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF) expression.

BACKGROUND AND OBJECTIVES: In oral tongue cancer, the degree of tumor invasion has a significant effect on the prognosis. We hypothesized that the destruction of extracellular matrix and neovascularization are related to tumor infiltration mechanism. By studying the tissues of early stage oral tongue cancer patients, we are intending to clarify the invasion-related factors. MATERIALS AND METHODS: To demonstrate the invasion process in early T-stage oral tongue cancer, the expressions of extracellular matrix destruction-related molecules (MMP-2, MMP-9) and neovascularization-related molecule (VEGF) were observed by immunohistochemical study. Also, staining of CD31 was done for quantification of neovascularization. We analyzed relationship between expression of each substances and tumor invasion depth, tumor free survival rates, and cervical lymph node metastasis rate. RESULTS: The expression rates of MMP-2, MMP-9, VEGF in 38 early oral cancer patients were 52.6%, 78.9%, and 52.6%, respectively. Significant correlation was found between the VEGF expression and microvessel density showed by CD31 immunohistochemical staining (P < 0.001). VEGF expressions were significantly related with tumor invasion depth (P = 0.002). The tumor-free survival rate of those patients with VEGF-positive tumors was significantly poorer than in those with VEGF-negative tumors (P = 0.019). CONCLUSIONS: These results indicate that VEGF is a useful marker for predicting the tumor invasion in patients with early tongue cancer.

Adult↗

PubMed2006

Lymphatic metastases to level IIb in hypopharyngeal squamous cell carcinoma.

OBJECTIVES: To evaluate the prevalence of level IIb lymph node (LN) metastasis and to identify potential clinical risk factors when level IIb metastatic diseases are present in patients with clinically node-negative (N0) and node-positive (N+) necks with hypopharyngeal squamous cell carcinoma (HPSCC). This will provide a basis for determining whether this region can be excluded in elective or therapeutic neck dissection in patients with HPSCC. DESIGN: Prospective analysis of a case series. SETTING: University hospital. PATIENTS: Fifty patients with HPSCC who underwent surgical treatment for a primary lesion and simultaneous neck dissection from January 1998 to February 2004. MAIN OUTCOME MEASURES: The incidences and clinical risk factors for level IIb LN metastasis and regional recurrence according to the presence or absence of pathologic LN involvement in level IIb. RESULTS: A total of 93 neck dissections were analyzed in this study. Of these dissections, 59 (63%) were elective and 34 (37%) were therapeutic. Three percent (2 of 59) of all N0 necks and 32% (11 of 34) of all N+ necks had level IIb LN metastases. Level IIb nodal metastases were significantly more prevalent in N+ necks (P=.007) than in N0 necks and in the presence of other positive LNs (P=.01) than in the absence of other positive LNs. Of the 35 patients with pathologic LNs, the regional recurrence rate was significantly higher in cases with positive level IIb LNs (33% [4 of 12]) than without (4% [1 of 23]; P=.04). CONCLUSIONS: Level IIb LN pads may be preserved during elective neck dissection in the treatment of patients with clinically N0 necks with HPSCC. This area should be removed during therapeutic neck dissection in the treatment of clinically N+ necks.

Adult↗

PubMed2006

Treatment of contralateral N0 neck in early squamous cell carcinoma of the oral tongue: elective neck dissection versus observation.

OBJECTIVES/HYPOTHESIS: Prophylactic treatment of contralateral N0 neck in early squamous cell carcinoma (SCC) of the oral tongue is a controversial issue. The aim of this study was to analyze the rates of occult metastases and their prognostic effects in stage I and stage II SCC of the oral tongue, and to compare the results of elective neck dissection to observation of the contralateral N0 neck in the treatment of these patients. STUDY DESIGN: Retrospective review. METHODS: We reviewed the medical records of 54 patients who were treated at Severance Hospital from 1992 to 2003 and had been diagnosed with stage I or stage II SCC of the oral tongue and had not received prior treatment. All patients underwent an ipsilateral elective neck dissection simultaneously with the primary lesion. The management of the contralateral N0 necks involved "watchful waiting" in 29 patients and elective neck dissection in 25 patients. Surgical treatment was followed by radiotherapy in 20 patients. Of these, seven patients belonged to the "observation" group who did not receive contralateral elective neck dissection. The follow-up period ranged from 3 to 110 months, with a mean of 56.3 months. Data were analyzed using the Kaplan-Meier method, the log-rank test, and the chi(2) test. RESULTS: Fifteen patients (28%, 15 of 54) had occult metastases. Of these, 14 patients (26%, 14 of 54) had ipsilateral pathologic metastases. The remaining case (4%, 1 of 25) had the only contralateral level II occult neck metastasis without ipsilateral metastasis. Disease recurred in 17 of 54 patients (31%). Of these, eight cases (47%, 8 of 17) had regional recurrences. All regional recurrences developed in the ipsilateral neck; there were no cases of contralateral neck recurrence. The 5-year actuarial disease-free survival rates were 82% for the "observation" group and 68% for the elective neck dissection group. This difference was not statistically significant (P = .182). The 5-year actuarial disease-free survival rates were 83% for the "observation" group when those patients who underwent radiotherapy were excluded (n = 22) and 68% for the elective supraomohyoid neck dissection group (n = 25), which showed no statistically significant difference (P = .127). CONCLUSIONS: This study showed that ipsilateral elective neck management is indicated for stage I and II SCC of the oral tongue. On the other hand, our series suggests that contralateral occult lymph node metastasis was unlikely in early-stage oral tongue SCC, and that there was no survival benefit for patients who underwent elective neck dissection in place of observation. Thus, it may not harmful to observe the contralateral N0 neck in the treatment of early oral tongue cancer.

Adult↗

PubMed2006

Management of contralateral N0 neck in pyriform sinus carcinoma.

OBJECTIVE: The hypopharynx has a rich lymphatic network that places patients with tumors of the hypopharynx at high risk for early dissemination of the disease into the cervical lymphatics. Therefore, ipsilateral elective neck dissection of clinically N0 neck in lateralized lesions of hypopharyngeal squamous cell carcinomas (SCCs) is widely accepted as a standard treatment. However, the management of the contralateral N0 neck is still controversial. The aim of this study was to evaluate the incidence and predictive factors of contralateral occult lymph node metastasis in pyriform sinus SCC. MATERIALS AND METHODS: We performed a retrospective analysis of 43 patients with N0 to 3 pyriform sinus SCC with contralateral clinically node-negative necks who had also received contralateral elective neck dissections from 1994 to 2003. Surgical treatment was followed by postoperative radiotherapy in 41 patients. The follow-up period ranged from 4 to 135 months (mean, 40 months). The Kaplan-Meier method and log-rank test were used to calculate the disease-specific survival rates and prognostic significance of contralateral occult lymph node metastasis. RESULTS: Contralateral occult lymph node metastases occurred in 16% (seven of 43) of the subjects. Twenty-six percent of the 27 subjects with clinically node-positive ipsilateral neck developed contralateral occult lymph node metastases, whereas 0% of the 16 subjects with N0 ipsilateral necks (P=.035) developed the disease. Moreover, in cases with primary site extension across the midline, the rate of contralateral occult neck metastasis was significantly higher (P=.010). However, there were no statistically significant differences in age, sex, early versus advanced T stage, number of ipsilateral positive nodes, lymph nodes with extracapsular spread, primary subsite of medial versus lateral pyriform sinus, pyriform sinus apex involvement, and growth type. Patients with no evidence of contralateral nodal cancer had significantly improved disease-specific survival over patients with any pathologically positive nodes (5-year disease-specific survival rate, 66% vs. 33%, P<.05). CONCLUSION: The patients with pyriform sinus SCC with clinically ipsilateral N+ neck and/or extension across the midline are at greater risk for contralateral occult neck metastases. Furthermore, patients who present with a contralateral metastatic neck have a worse prognosis than those staged as N0. Therefore, we advocate bilateral neck treatment in patients with pyriform sinus SCC with clinically ipsilateral node metastases and/or extension across the midline.

Adult↗

PubMed2005

Combination of mutated herpes simplex virus type 1 (G207 virus) with radiation for the treatment of squamous cell carcinoma of the head and neck.

G207 is an oncolytic herpes simplex virus (HSV) with deletions at both gamma134.5 loci and a LacZ gene insertion inactivating the HSV ribonucleotide reductase gene. Ionising radiation induces the growth arrest-inducible gene, GADD34, and ribonucleotide reductase. GADD34 is a protein that correlates with apoptosis following radiation and has homology with the G207 gamma134.5 gene. We hypothesised that the combination of radiotherapy with G207 may have a potentiating effect on viral replication and anti-tumour efficacy. The purpose of this study was therefore to evaluate the combination of G207 with radiation therapy to treat head and neck tumours. The cytotoxicity of G207 was tested in six head and neck squamous carcinoma cell lines, in the presence or absence of irradiation. For in vivo experiments, flank tumours in C3H/HeJ mice or in nude mice were treated with direct injections of G207, with or without radiation. All head and neck squamous cancer cell lines tested demonstrated significantly increased antitumour effects with the combination of G207 virus and radiation therapy compared with each individual modality (P<0.01). Furthermore, the combination treatment effect was better than the expected additive effect of the two therapies in combination. Even the radiation-resistant cell lines (SCC25, MSKQLL2, SCCVII) were susceptible. The combination of direct G207 injection with radiation therapy suppressed human and murine squamous cell carcinoma growth significantly (P<0.05 and P<0.001) compared with controls or single modality therapy. G207 enhanced the effectiveness of radiation therapy and low-dose radiation potentiated the effectiveness of G207 viral therapy in head and neck cancer. These findings suggest a potential clinical application for this combined therapy as treatment for radiation-resistant head and neck cancers.

Animals↗

PubMed2005

Management of contralateral N0 neck in tonsillar squamous cell carcinoma.

OBJECTIVES: It is well established that tonsillar squamous cell carcinomas have a high probability of disseminating to the neck. An ipsilateral neck treatment is mandatory during initial treatment of stages II to IV tonsillar carcinomas. However, as of yet, no consensus exists whether to perform elective contralateral neck management. MATERIALS AND METHODS: A retrospective analysis of 43 N0-3 tonsillar cancer patients with contralateral clinically negative necks from 1992 to 2002 was performed. All patients had a contralateral elective neck dissection. Surgical treatment was followed by postoperative radiotherapy in 33 patients. The follow-up period ranged from 2 to 120 (mean 38) months. The Kaplan-Meier method and log-rank test were used to calculate the disease-specific survival rates and prognostic significance of contralateral occult lymph node metastasis. RESULTS: Clinically negative, but pathologically positive, contralateral lymph nodes occurred in 16% (7 of 43). Of the 33 cases with an ipsilateral node positive neck, contralateral occult lymph node metastases developed in 21% (7 of 33), in contrast with 0% in ipsilateral N0 necks. On the basis of the clinical staging of the tumor, 5% (1 of 22) of the cases showed lymph node metastases in T2 tumors, 36% (5 of 14) in T3, and 25% (1 of 4) in T4. None of the T1 tumors (3 cases) had pathologically positive lymph nodes (T1 + T2 vs. T3 + T4, P < .05). Patients with no evidence of contralateral nodal cancer had significantly improved disease-specific survival over patients with any pathologically positive nodes (5 year disease-specific survival rate 92% vs. 28%, P = < .05). CONCLUSION: The risk of contralateral occult neck involvement in above T3 staged tonsillar squamous cell carcinomas with unilateral metastases was high (approximately 21%), and patients who present with a contralateral metastatic neck have a worse prognosis than those who are staged as N0. Therefore, we advocate an elective contralateral neck treatment in tonsillar squamous cell carcinoma patients with ipsilateral node metastases.

Adult↗

PubMed2004

Electrically driven single-cell photonic crystal laser.

We report the experimental demonstration of an electrically driven, single-mode, low threshold current (approximately 260 microA) photonic band gap laser operating at room temperature. The electrical current pulse is injected through a sub-micrometer-sized semiconductor wire at the center of the mode with minimal degradation of the quality factor. The actual mode of interest operates in a nondegenerate monopole mode, as evidenced through the comparison of the measurement with the computation based on the actual fabricated structural parameters. As a small step toward a thresholdless laser or a single photon source, this wavelength-size photonic crystal laser may be of interest to photonic crystals, cavity quantum electrodynamics, and quantum information communities.

Journal Article↗

PubMed2003

Changes of esophageal motility after total laryngectomy.

OBJECTIVE: Total laryngectomy completely interrupts the continuity of the proximal digestive tract and may lead to derangement in esophageal motility. The purpose of this investigation was to find out how total laryngectomy changes the resting and the maximum contracting pressures of the upper esophageal sphincter muscle and how it affects the coordination of the contraction and the relaxation between the pharynx and the upper esophageal sphincter muscles. If changes in the function of the upper esophageal sphincter muscle should occur, this study will also demonstrate how it affects the motility of the esophagus and the lower esophageal sphincter muscle. METHODS: In an attempt to explain postoperative motility changes, the stationary pull through method of manometric evaluation was used to quantify the alteration in esophageal motility. For the manometric evaluation of the esophagus, a polyethylene catheter with 8 internal tubes was used. The study was performed on a group of 15 patients with total laryngectomy and 15 people without esophageal disease or symptoms as the control group. RESULTS: There was a statistically significant difference between the laryngectomy group and the control group for both the resting and maximum contraction pressures as well as for coordination and relaxation of the upper esophageal sphincter. (P < 0.05) In the laryngectomy group, 3 patients who complained of postoperative dysphasia showed more severe functional changes. The proximal esophageal body pressure and peristaltic waves were significantly decreased in the laryngectomy group. No significant difference between the laryngectomy group and the control group was noted in terms of the lower esophageal resting sphincter pressure and the postdeglution pressure. There also was no significant difference between the two groups in the degree of lower esophageal sphincter coordination and relaxation. CONCLUSION: From these results, it may be concluded that interruption of the cricopharyngeal muscle and pharyngeal plexus after laryngectomy not only may produce local derangement of upper esophageal sphincter function but also may produce abnormalities in peristalsis of the proximal esophageal body. However, the function of lower esophageal sphincter did not show any significant difference between the laryngectomy group and the control group.

Esophageal Motility Disorders↗

PubMed2002

Oncolytic herpesvirus effectively treats murine squamous cell carcinoma and spreads by natural lymphatics to treat sites of lymphatic metastases.

Oncolytic herpesviruses have significant antitumoral effects in animal models when delivered directly to established tumors. Lymphatic metastases are a common occurrence for many tumor types. This study investigates the potential of an attenuated, replication-competent, oncolytic herpes simplex virus (NV1023) both to treat a primary tumor by direct injection and to travel through the lymphatic system to treat metastatic tumor within the lymph nodes draining lymph from the site of primary cancer. Isosulfan blue dye was injected into murine auricles to determine normal lymphatic drainage patterns and demonstrated consistent blue staining of a group of ipsilateral cervical lymph nodes. Auricular injections of NV1023 resulted in viral transit to these lymph nodes as measured by 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside histochemistry and viral plaque assay. An oncolytic herpesvirus (NV1066) expressing green fluorescent protein also demonstrated viral transit from the auricle to the cervical lymph nodes on fluorescence microscopy. Using the SCC VII cell line, a novel murine model of auricular squamous cell carcinoma was developed with an approximately 20% incidence of cervical lymph node metastases. Delivery of NV1023 or NV1066 to the surgical beds after excision of auricular SCC VII tumors resulted in successful viral infection of metastatic SCC VII cells within the cervical lymph nodes. After a 7-week follow-up, significantly enhanced locoregional control (p < 0.05, Fisher exact test) and disease-free survival (p < 0.05, log rank test) were evident with NV1023 treatment. This study demonstrates that the delivery of an oncolytic herpesvirus to a primary tumor site after surgical excision may have a significant impact on reducing both primary site recurrence and regional nodal metastases.

Animals↗

PubMed2002

Mucociliary differentiation according to time in human nasal epithelial cell culture.

Knowledge of the state of differentiation, cell phenotype, and expression of genes for mucus production at the time of study is important because these may vary at different times during the culture period. The primary purpose of this study was to determine whether the number of ciliated cells increases as a function of differentiation in NHNE cells. If we observed an increase in the number of ciliated cells, the composition ratio of ciliated and secretory cells according to the culture duration was determined. The levels of mucin and lysozyme secretion and their gene expression at this time were also examined. The presence of ciliated cells was not evident up to 2 days after confluence. However, 3.1 +/- 0.2 %, 7.4 +/- 0.5 %, and 14.5 +/- 0.6 % of the cells were ciliated on the 7th, the 14th, and the 28th day after confluence, respectively. Meanwhile, the percentage of secretory cells were 35.6 +/- 2.8 %, 32.8 +/- 2.5 %, 32.8 +/- 2.5 %, and 49.4 +/- 1.4 % on the 2nd, the 7th, 14th, and 28th day after confluence. The amount of secreted mucin showed an abruptly increasing pattern by the 14th day after confluence but showed no significant changes thereafter. The amount of secreted lysozyme increased as a function of differentiation. MUC5AC and MUC5B mRNA were mainly expressed between the 7th and the 14th day after confluence with relatively weak MUC8 and lysozyme expression. By the 28th day after confluence however, as the MUC5AC mRNA expression became weaker, MUC5B, MUC8, and lysozyme mRNA expression became stronger. In conclusion, we speculate that in in vitro studies with NHNE cells, the time point of treatment should vary according to the purpose of the study. In addition, the MUC5B and MUC8 gene may play an important role in mucin secretion in fully differentiated human nasal epithelial cells.

Cell Differentiation↗