• International Journal of Oral Biology
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• v.32 no.3
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• pp.93-101
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• 2007

Cell behavior of the transformed cells is known to affect by interaction with extracellular matrix (ECM) proteins and integrin. To investigate the alterations of both integrin expression and cell-matrix interaction during neoplastic conversion of human oral kerationcytes, we studied expression levels of integrin subunits by flow cytometry and cellular responses to the ECM proteins in normal human oral keratinocytes (NHOKs), HPV-immortalized HOK-16B line, and three oral cancer cell lines established from HOK-16B line, CTHOK-16B-BaP, CTHOK-16B-DMBA, and CTHOK-16B-Dexa lines. The expression levels of ${\alpha}\;and\;{\beta}$ integrin subunits were shown decreased tendency in human oral keratinocytes undergoing immortalization and tumorigenic transformation except CTHOK-16B-DMBA line tested. Although ${\alpha}v{\beta}6$ integrin is known to be highly expressed in squamous cell carcinomas, and the altered integrin expression is suspected to be associated with cellular carcinogenesis, ${\alpha}v$ integrin subunit and ${\alpha}v{\beta}6$ integrin did not express in oral cancer cell lines tested. Cell behavior to the ECM proteins in HOK-16B line was generally similar to that of exponentially proliferating NHOKs. The adhesion activity profiles of type I collagen were very similar to that of its laminin counterparts, but fibronectin showed minimal adhesion activity under our conditions compared to the BSA control. The ability of the CTHOK-16B-BaP line to spread upon type I collagen and laminin markedly decreased, but migration was notably increased on type I collagen. In contrast, CTHOK-16B-DMBA and CTHOK-16B-Dexa lines spread less but migrated more upon type I collagen than immortalized HOK-16B line. These data indicate that downregulation of integrin subunits causes the changes of cellular responses to the ECM proteins during neoplastic conversion of human oral keratinocytes, and that cellular responses to the ECM proteins in oral cancer cell lines established by exposing different carcinogens are variable according to chemical carcinogens treatment.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.35 no.5
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• pp.287-293
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• 2009

Cell survival is the result of a balance between programmed cell death and cellular proliferation. Cell membrane receptors and their associated signal transducing proteins control these processes. Of the numerous receptors and signaling proteins, epidermal growth factor receptor (EGFR) is one of the most important receptors involved in signaling pathways implicated in the proliferation and survival of cancer cells. EGFR is often highly expressed in human tumors including oral squamous cell carcinomas, and there is increasing evidence that high expression of EGFR is correlated with poor clinical outcome of common human cancers. Therefore, we examined the antiproliferative activity of gefitinib, epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI), in head and neck cancer cell lines. SCC-9, KB cells were cultured and growth inhibition activity of gefitinib was measured with MTT assay. To study influence of gefitinib in cell cycle, we performed cell cycle analysis with flow cytometry. Western blot was done to elucidate the expression of EGFR in cell lines and phosphorylation of EGFR and downstream kinase protein, Erk and Akt. Significant growth inhibition was observed in SCC-9 cells in contrast with KB cells. Also, flow cytometric analysis showed G1 phase arrest only in SCC-9 cells. In Western blot analysis for investigation of EGFR expression and downstream molecule phosphorylation, gefitinib suppressed phosphorylation of EGFR and downstream protein kinase Erk, Akt in SCC-9. However, in EGFR positive KB cells, weak expression of active form of Erk and Akt and no inhibitory activity of phosphorylation in Erk and Akt was observed. The antiproliferative activity of gefitinib was not correlated with EGFR expression and some possibility of phosphorylation of Erk and Akt as a predictive factor of gefitinib response was emerged. Further investigations on more reliable predictive factor indicating gefitinib response are awaited to be useful gefitinib treatment in head and neck cancer patients.

• Radiation Oncology Journal
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• v.8 no.2
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• pp.177-182
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• 1990

From 1984 to 1988, fourty two patients with nasopharyngeal cancer were treated at the Department of Radiation Oncology in Kyungpook National University Hospital. Thirteen patients refused treatment and the median survival time was 7.8 months. Twenty nine patients received a full course of radiation at least 70 Gy to the primary site and 60 Gy to the nodal sites. These patients were all belonged to stage III or IV, The local control rate was $75\% in squamous cell carcinomas, and all the patients with lymphoepithelioma showed a complete response. Overall locoregional failure was $27.6\%. Distant metastasis was the predominant pattern of failures; 4/6 in lymphoepithelioma, 4/10 En squamous cell carcinoma. The Three-year-survival rate for squamous cell carcinoma was $40.5\%$, and for lymphoepithelioma $25.9\%, respectively. This may be due to the more frequent distant metastases in lymphoepithelioma and ineffective chemotherapy. No survival correlation was found with the level of neck node involvement. Though adjuvant chemotherapy was found to be of no benefit in overall survival, more prudent and aggressive chemotherapy would be necessary.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.26 no.4
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• pp.337-344
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• 2000

Germ-line mutations at DNA repair loci confer susceptibility to colon cancer in hereditary non-polypopsis colorectal cancer. Somatic loss of DNA mismatch repair gene has been reported in a large variety of other tumor types. Replication errors(RERs) judged by microsatellite instability(MSI) and its associated mutations have been recognized as an important mechanism in various tumor types. To investigate associations between MSI and oral squamous cell carcinoma, the frequency of MSI using 12 microsatellite markers were analyzed for the series of oral tumors. Of 17 tumors, 8 cases(47%) did not show instability at any of the 12 loci; 5(29%) showed instability at $2{\sim}3$ loci; and 4(24%) showed instability above 4 loci. The 4 cases showing widespread MSI did not differ from those without evidence of instability in terms of age at diagnosis, degree of differentiation, metastasis to lymph node, tumor location or the presence of mutations in the p53 tumor suppressor gene. DCC and D17S 796 were the most frequently detected in MSI analysis. There were no correlation between smoking and MSI frequency, instead, smoking was suggested to increase the mutation rate of p53 and development of oral carcinomas.

• Journal of Trauma and Injury
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• v.20 no.1
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• pp.52-56
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• 2007

Marjolin's ulcer is a rare and often-aggressive cutaneous malignancy that arises in previously traumatized or chronically inflamed skin, particularly after burns. We experienced two cases after burns. Case I involved a forty eight year-old man who had suffered from a flame burn at the parietal scalp area, where had been initially described three years earlier as a full-thickness wound including the pericranium. The man consulted us for a persistent ulcerative and infected wound on the burned lesion during the last 24 months, which turned out on the contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI) to be the squamous cell carcinoma with involving the skull and the dura mater. Although the posterior auricular lymph node was enlarged on the ipsilateral side, recent positron emission tomography (PET) CT did not show any metastatic lesion. It was impossible for us to resect the intracranial involvement of the tumor radically, and the postoperative PET CT still showed a focal fluorodeoxyglucose (FDG) uptake around the wall of the superior sagittal sinus. We think that an aggressive combined approach is essential for treatment in early stages for a high success rate, before the intracranial structures are involved because there is no consensus on the treatment for advanced disease, and the results are generally poor. Case 1 also did not involve a radical resection because of the intracranial invasion to the wall of superior sagittal sinus and the possibility of damage to the major cortical veins. He received adjuvant radiotherapy and must be followed periodically. Case 2 involved an eighty six year-old women who suffered from a painful scalp ulcer lesion after flame burns three years earlier. Unlike case 1, neither tumor infiltration into the dura nor lymph node enlargement was observed on the contrast-enhanced computed tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET) CT. We did a radical resection of the tumor, including the involved bone, and a cranioplasty with bone cement.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6239-6244
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• 2012

Background: The basal cell carcinoma (BCC) is the most common non-melanoma skin cancer (NMSK). BCC might develop because of the faulty cell cycle arrest. $p15^{INK4b}$ is a tumor suppressor gene, involved in cell cycle arrest and inactivated in most human cancers. The role of $p15^{INK4b}$ protein expression in the genesis of BCC is as yet unknown. In a previous study we showed the absence of $p15^{INK4b}$ expression in the majority of tissue microarray cores of cutaneous squamous cell carcinoma (SCCs), another type of non-melanoma skin cancer, indicating that $p15^{INK4b}$ could possibly be involved in the pathogenesis of cutaneous SCC. The aim of this study was to investigate $p15^{INK4b}$ protein expression in BCCs. Materials and Method: Protein expression of $p15^{INK4b}$ in 35 cases of BCC tissue arrays and 19 cases of normal human skin tissue was studied using an immunohistochemical approach. Results: The expression of $p15^{INK4b}$ was not significantly different in the BCC cases as compared with normal human skin (p=0.356; p>0.05). In addition, there were no significant relationship between clinicopathologic variables of patients (age and sex) and $p15^{INK4b}$ protein expression. Conclusions: Our finding may indicate that $p15^{INK4b}$ protein expression does not play a role in the genesis of BCC.

• Tuberculosis and Respiratory Diseases
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• v.68 no.1
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• pp.16-21
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• 2010

Background: Lung cancer is usually diagnosed at an advanced stage, resulting in a poor prognosis. The detection of these lesions at an earlier stage would be a clear benefit to patients. However, it is extremely difficult to detect carcinomatous lesions in the bronchial mucosal sites during a routine bronchoscopy. Methods: This study employed a novel optical technique, known as narrowband imaging (NBI), which allows noninvasive visualization of the microvascular structure of an organ's surface using reflected light. Results: Narrow band imaging was performed on 10 patients who were radiologically suspicious or had a high risk of lung cancer. The median age of the patients was 57.5 years (range, 44~81 years), and 80% of the patients were male. All lesions showed a microvascular proliferation pattern (dotted, tortuous and abruptly ending vessel) on the magnified NBI. Two lesions were confirmed histologically to be adenocarcinoma and the remaining lesions were squamous cell carcinomas. Two lesions were confirmed histologically to be a carcinoma in situ. Conclusion: NBI is a promising and potentially powerful tool for identifying carcinomas at an earlier stage or a central lesion during a routine bronchoscopy examination.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.5749-5754
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• 2015

Cervical carcinoma is the main cause of cancer-related mortality in women and is correlated with more than 15 risk cofactors, including infection of cervical cells with high-risk types of HPV (hrHPV). Indeed, both aberrant methylation of the RASSF1A promoter and hrHPV infection are often observed in cervical carcinomas. The purpose of our meta-analysis was to evaluate the role of RASSF1A promoter methylation and hrHPV infection in cervical cancer. Our meta-analysis involved 895 cervical cancer patients and 454 control patients from 15 studies. Our results suggested that RASSF1A promoter hypermethylation increased the risk of cervical cancer (OR=9.77, 95%CI=[3.06, 31.26], P=0.0001, $I^2=78%$). By grouping cases according to cancer subtypes, we found that HPV infection was higher in cervical squamous cell carcinomas (SCCs) than in cervical adenocarcinomas/adenosquamous cancers (ACs/ASCs) (OR=4.00, 95%CI=[1.41, 11.30], P=0.009, $I^2=55%$). Interestingly, HPV infection tended to occur in cervical cancers with relatively low levels of RASSF1A promoter methylation (OR=0.59, 95%CI=[0.36, 0.99], P=0.05, I2=0%). Our study provides evidence of a possible interaction between HPV infection and RASSF1A promoter methylation in the development of cervical cancers.

• Journal of Chest Surgery
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• v.25 no.12
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• pp.1530-1536
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• 1992

From January 1984 to December 1991, One hundred sixty five patients with carcinomoa of the esophagus were treated surgically at the department of Thoracic and Cardiovascular Surgery, Seoul National University Hospital. Among them, hospital records were available in 121 patients and were included in this study. There were 115 men and 6 women, with ages ranging from 40 years to 79 years[mean age of 59.2 years]. The most frequent preoperative symptoms included dysphagia[72.7%], weight loss[60.3%], chest pain or discomfort[14.9%], general malaise[13.2%]. All were treated surgically: 100 patients were managed by curative or palliative resection with reconstruction, and 6 by palliative bypass surgery. In 15 patients, explorative thoracotomy or laparotomy was only done due to unresectability. [operability: 87.6%, resectability: 82.6%] All specimens[those from resectable 100 cases] were sent to pathology, and histopathologic examinations were done; squamous cell carcinomas were found in 95 cases, adenocarcinoma in l. Adenosquamous carcinomas were found in 3, and malignant melanoma in l. Postoperative complications occurred in 34 cases; anastomotic site leakage[10], which was followed by empyema in 9 of them, wound problem[7], hepatic failure[6], pneumonia [3], post-operative bleeding[3], chylothorax[2], post-operative stricture[2], sepsis[1], and tracheobronchial fistula[1]. Hospital deaths were in 6 cases[Hospital mortality: 5.0%]. During the follow up period, 26 patients were proven to be recurrence of cancer locally or distantly. The one, two, and five-year actuarial survival raf.es were 71.3$\pm$4.5%, 57.4$\pm$5.6%, 34.7$\pm$8.9%, respectively. The data from this study suggested that esophagectomy with reconstruction of gastrointestinal tract could be performed with a low operative mortality and a few serious postoperative complications and achieved reasonable long term palliation for carcinoma of the esophagus.

• Archives of Plastic Surgery
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• v.41 no.6
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• pp.654-660
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• 2014

Background Reactive oxygen species (ROS) damages cell molecules, and modifies cell signaling. The nuclear factor E2-related factor (Nrf2) is a critical transcription regulator, which protects cells against oxidative damage. Nrf2 expression is increased in a large number of cancers. However, little information has been reported regarding the expression of Nrf2 in skin cancers. Hence, we explored the expression of Nrf2 protein in skin cancers. Methods The Nrf2 protein expression in 24 specimens, including 6 malignant melanomas (MM), 6 squamous cell carcinomas (SCC), 6 basal cell carcinomas (BCC), and 6 normal skin tissues, was evaluated by western blotting. Immunohistochemical staining was performed. The expression of Kelch-like ECH-associated protein 1 (Keap1), the key regulator of Nrf2, was also analyzed by western blotting. Results Small interfering RNA transfection to the melanoma cell line G361 confirmed that an approximately 66 kDa band was the true Nrf2 band. The western blot revealed that the Nrf2 protein was definitely expressed in normal skin tissues, but the Nrf2 expression was decreased in MM, SCC, and BCC. Immunohistochemical examination showed that expression of Nrf2 was decreased in all skin cancer tissues compared to the normal skin tissues. Keap1 was not expressed in all malignant skin tumors and normal skin tissues by western blot. Conclusions ROS was increased in various types of cancers which proteins were highly expressed or underexpressed. This study demonstrated that the expression of Nrf2 protein was down-regulated in human malignant skin tumors. We suggest that decreased expression of Nrf2 is related to skin cancers.