• International Journal of Oncology
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• v.54 no.6
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• pp.2117-2126
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• 2019

Transforming growth factor-β1 (TGF-β1) is a multifunctional cytokine that functions as a growth suppressor in normal epithelial cells and early stage tumors, but acts as a tumor promoter during malignant progression. However, the molecular basis underlying the conversion of TGF-β1 function remains largely undefined. X-linked inhibitor of apoptosis-associated factor 1 (XAF1) is a pro-apoptotic tumor suppressor that frequently displays epigenetic inactivation in various types of human malignancies, including colorectal cancer. The present study explored whether the anti-apoptotic effect of TGF-β1 is linked to its regulatory effect on XAF1 induction in human colon cancer cells under stressful conditions. The results revealed that TGF-β1 treatment protected tumor cells from various apoptotic stresses, including 5-fluorouracil, etoposide and γ-irradiation. XAF1 expression was activated at the transcriptional level by these apoptotic stresses and TGF-β1 blocked the stress-mediated activation of the XAF1 promoter. The study also demonstrated that mitogen-activated protein kinase kinase inhibition or extracellular signal-activated kinase (Erk)1/2 depletion induced XAF1 induction, while the activation of K-Ras (G12C) led to its reduction. In addition, TGF-β1 blocked the stress-mediated XAF1 promoter activation and induction of apoptosis. This effect was abrogated if Erk1/2 was depleted, indicating that TGF-β1 represses XAF1 transcription through Erk activation, thereby protecting tumor cells from apoptotic stresses. These findings point to a novel molecular mechanism underlying the tumor-promoting function of TGF-β1, which may be utilized in the development of a novel therapeutic strategy for the treatment of colorectal cancer.

• The Korean Journal of Cytopathology
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• v.3 no.1
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• pp.1-11
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• 1992

From the one hundred forty eight patients with evidence of biliary tract obstruction, 275 bile samples were obtained from percutaneously placed biliary drainage catheters. Of the 148 patients, ova of Clonorchis sinensis were demonstrated in 17 patients (11.5%), with the epithelial cells. Among them, one case also demonstrated coexisting adenocarcinoma. In 105 patients, the medical records were available for review and the clinical diagnoses were malignancy in 99 patients and benign lesion in 6 patients. Of the 99 patients in which clinico-radiologic diagnosis were malignant, cytologic results were positive in 23.2%. Dividing the patients Into two groups, the ones with tumor of bile duct origin (group I) and the others with tumors producing extrinsic compression of bile duct, such as periampullary carcinoma, pancreas head carcinoma or metastatic carcinoma in lymph nodes from tumors of adjacent organs (group II), the cytologic results were positive in 37% and 11.6%, respectively. In patients with histologic confirmation, the positive correlation was found in 50% and 20% in group I and group II, respectively, with remarkable difference between two groups. There were no false positives in cytologic diangosis. The overall concordance rate of cytologic diagnosis with diagnosis of clinical investigation in both benign and malignant lesions was 27.6% and the diagnostic specificity was 100%.

• Journal of Chest Surgery
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• v.40 no.8
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• pp.564-568
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• 2007

Background: Pulmonary hamartomas are the most common form of pulmonary benign tumors, and they occur in approximately $2{\sim}5%$ of all pulmonary neoplasm. However, only a few reports have been published on the clinical characteristics of pulmonary hamartoma in Korea. Material and Method: The charts, X-rays and pathological specimens of 37 pulmonary hamartoma patients who were diagnosed by a pathological examination from January of 2000 to May of 2005 at the Catholic Medical Center were retrospectively reviewed. Result: The peak incidence of the tumor occurred in the seventh decade of life (32.4%), There were 23 men (62.6%) and 14 women (37.8%), with mean age of 55.6 years. Twenty-six patients (70.3%) were asymptomatic and 11 patients (29.7%) had symptoms. A total of 29 tumors (78.4%) were parenchymal, and 8 (21.6%) were endobronchial. Twenty cases (54.1%) were in the right lung and 17 cases (45.9%) were in the left lung. The right lower lobe was most commonly involved. Thirty-two (86.5%) hamartomas were diagnosed by surgical resection, 4 cases (10.8%) were diagnosed by bronchoscopic biopsy and 1 case (2.7%) was diagnosed by a fine needle aspiration biopsy. Thirty-four hamartomas (91.9%) were managed by surgical resection without complication. No recurrence or malignant changes were seen during the follow up period. Conclusion: Pulmonary hamartomas are most common in males during their fifth to seventh decade and they more commonly involve the right lung. No recurrence or malignant changes were seen during the follow up period.

• The Journal of the Korean bone and joint tumor society
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• v.3 no.2
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• pp.80-88
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• 1997

Malignant tumors of extremeties involving major neurovascular structures have been treated by amputation. However recent development of diagnostic tools(CT, MRI etc.), surgical techniques, anticancer chemotherapeutic agents, and radiation techniques allow surgeons to treat malignant tumors in the limb without amputation. It has been reported that a local application of low-heat to the tissue with tumor can kill tumor cells. It is, however, not known if the attendant neural and vascular injuries may be recovered. The present study was, therefore, undertakn to address this question in rabbit sciatic nerves. A low-heat injury to the sciatic nerve was induced by perfusing the nerve with $60^{\circ}C$ saline for 30 minutes and the courses of functional and morphological recovery of the nerve were evaluated for 16 weeks. The results are summerized as follows : 1. In the electromyographic nerve conduction test the average amplitude was markedly attenuated at 4 and 8 weeks after the low-heat treatment, but it progressively increased to the level 89.5% of the control at 16 week post-treatment. The average latency in the control group was 0.62 msec. The latency in the experimental group was much longer than this at 4 and 8 week post-treatment, but it progressively reverted to the control level, showing 0.622 msec at 16 weeks. 2. In the needle EMG, many fibrillation potentials and positive sharp waves were appeared until 8 weeks post-treatment. After 16 weeks, however, no fibrillation potential was observed. 3. In the early phase of post-treatment period, the myelinated nerve fibers contained many vacuoles and the number of myelinated nerve fibers appeared to be considerably reduced. However, as time goes myelinated nerve fibers were regenerated, such that after 16 weeks the histologic appearance of the nerve was similar to that of the control group.

• Journal of Korean Neurosurgical Society
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• v.30 no.3
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• pp.263-271
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• 2001

Objective : Glioblastomas, the most common type of primary brain tumors, are highly invasive and cause massive tissue destruction at both the tumor invading edges and in areas that are not in direct contact with glioma cells. As a result, patients with high-grade gliomas are faced with a poor prognosis. Such grim statistics emphasize the need to better understand the mechanisms that underlie glioma invasion, as these may lead to the identification of novel targets in the therapy of high grade gliomas. Protein kinase C(PKC) is a family of serine/threonine kinases and an important signal transduction enzyme that conveys signals generated by ligand-receptor interaction at the cell surface to the nucleus. PKC appears to be critical in regulating many aspects of glioma biology. The purpose of this study was to assess accurately the role of PKC in the invasion regulation of human gliomas based on hypothesis that protein kinase C(PKC) is functional in the process of glial tumor cell invasion. Method : To test this hypothesis, U-87 malignant glioma cell line intracellular PKC levels were up and down regulated and their invasiveness was tested. Intracellular PKC level was characterized using PKC activity assays. Invasion assays including barrier migration and spheroid confrontation were used to study the relationship between PKC concentration and invasiveness. Result : The cell line which were treated by PKC inhibitor tamoxifen and hypericin exhibited decreased PKC activity and decreased invasive abilities dose dependently both in matrigel invasion assay and tumor spheroid fetal rat brain aggregates(FRBA) confrontation assay. However, the cell line that was treated by PKC activator 12-O-tetradecanylphorbol-13acetate(TPA) did not exhibit increases in either PKC activity or invasive ability. Conclusion : These studies suggest that PKC may be a useful molecular target for the chemotherapy of glioblastoma and other malignancies and that a therapeutic approach based on the ability of PKC inhibitors may be helpful in preventing invasion.

• Radiation Oncology Journal
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• v.26 no.1
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• pp.56-64
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• 2008

Purpose: Cathepsin D(CD) is a lysosomal acid proteinase that is related to malignant progression, invasion, and a poor prognosis in several tumors. The aim of this study was to evaluate the prognostic clinical significance of CD and p53 expression in pretreatment biopsy specimens from patients with locally advanced rectal cancer who were treated with preoperative chemoradiation. Materials and Methods: Eighty-nine patients with locally advanced rectal cancer(cT3/T4 or N+) were included in this study. Preoperative chemoradiation consisted of a dose of 50.4 Gy of pelvic radiation and two concurrent cycles of administration of 5-fluorouracil and leucovorin. Surgery was performed six weeks after chemoradiation. CD and p53 expression in pretreatment formalin-fixed paraffin-embedded tumor biopsy specimens were assessed by immunohistochemical staining using a CD and p53 monoclonal antibodies. The threshold value for a positive stain in tumor tissue and stromal cells was 1+ intensity in 10% of the tumors or stromal cells, respectively. Results: Positive CD expression was found in 57(64%) of the tumors and 32(35%) of the stromal cell specimens. There was no association with CD expression of the tumor or stromal cells and patient characteristics. There was a correlation between tumor CD expression with stromal cell CD expression(p=0.01). Overexpression of p53 was not a significant prognostic factor. The 5-year overall survival(OS) and disease-free survival(DFS) rates were not different between tumor CD-negative and positive patient biopsy samples(69% vs. 65%, 60% vs. 61%, respectively). The 5-year OS rates in the tumor-negative/stromal cell-negative, tumor-negative/stromal cell-positive, tumor-positive/stromal cell-negative and tumor-positive/stromal cell-positive biopsy samples were 75%, 28%, 62%, and 73%, respectively. Stromal cell staining only without positive tumor staining demonstrated the worst overall survival prognosis for patients(p=0.013). Conclusion: Overexpression of p53 in rectal biopy tissue was not associated with prognostic significance. In the pretreatment biopsy specimens, an exclusive increase in CD expression in stromal cells without tumor expression was related to poor overall survival in patients with locally advanced rectal cancer treated with preoperative chemoradiation.

• Journal of Chest Surgery
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• v.30 no.8
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• pp.780-785
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• 1997

Mediastinal tumor had been fascinated by its location on heart, great vessels, esophagus, and nervous tissue, its convenience of surgical treatment and superiority of its operative result. Between January 1989 and June 1995, eighty-seven patients with mediastinal tumor which were treated surgically in the Department of Thoracic and Cardiovascular Surgery, Asan Medical Center, School of Medicine, University of Ulsan. To provide the appropriate surgical management of mediastinal tumor, the demographic data, diagnostic evaluation, clinical presentation, location, size, operative finding and histopathologic distribution were reviewed and we analyzed relativity between invasiveness in chest computed tomographic finding or invasiveness on operative finding and histopathologic invasiveness. The anterosuperior mediastinum was the most commonly involved site of a mediastinal tumor(57%), followed by the posterior mediastinum(35%) and middle mediastinum(8%). The most frequently encountered tumors were thymic neoplasia(31%), followed by primary cyst(22%), neurogenic tumor(22%) and teratoma(10%) in decreasing order of frequency. Histopathologically invasive tumors were present in 17 patients(20%) and its site included anterosuperior mediastinum(16%) and posterior mediastinum(4%). All patients in this study underwent chest CT. In chest CT's finding, 15 patients(17%) showed invasiveness. A total excision of the tumor was performed 80 patients(92%), subtotal excision 6 patients(7%) and biopsy only 1 patient(2%). In operative finding, 14 patients(16%) were suspected invasiveness. The mean size of the tumor was 6.0$\pm$ 3.2cm. In anterosuperior mediastinum, the mean size was 6.2$\pm$3.1cm, in middle mediastinum, it was 3.9$\pm$1.1cm, in posterior mediastinum, it was 5.8$\pm$2.6cm. In malignant tumors, the mean size was 7.3$\pm$4.6cm, in benign tumor, it was 5.5$\pm$2.6cm(P<0.05). Relativity between histopathological invasiveness(17 patients) and invasiveness in chest CT's finding(15 patients) included sensitivity 35%, specificity 87% and predictability 35%, relativity between histopathological invasiveness(17 patients) and invasiveness on operative finding included sensitivity 52%, specificity 93% and predictability 64%. In conclusion, since it was proved that the compatibility of preoperative chest CT findings or operative findings and histopathological invasiveness is quite low, it is considered that wide excision of the mediastinal tumor except cystic lesion including adjacent tissues would yield better postoperative results.

• Korean Journal of Head & Neck Oncology
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• v.14 no.2
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• pp.182-190
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• 1998

Background: Most of the cancers of maxillary sinus are the squamous variety, but various histopathologic types of malignant tumor can occur in the maxillary sinus. These non-squamous cell tumors have quite different patterns of clinical behavior compared with squamous variety, such as invasive characters, route of metastasis, treatment modality, and so on. Objectives: The authors intend to establish the clinical characteristics and treatment modalities of non-squamous cell tumors of the maxillary sinus. Material and Methods: We experienced 16 cases of non-squamous cell tumors arisen from the maxillary sinus during the 10-year period from 1987 to 1996. We analyzed their clinical features, therapeutic modalities and results with review of literatures. Results: According to AJCC TNM system, 13 patients presented with $T_{1-2}$, 3 with $T_{3-}4$, Two patients were treated with surgery after radiotherapy, 3 patients with surgery after chemotherapy and radiotherapy, 4 patients with chemotherapy and radiotherpy, 5 patients with chemotherapy and radiotherapy after surgery. Conclusion: In cases of adenoid cystic carcinoma, adenocarcinoma and sarcoma, we believe that the best form of therapy is wide surgical excision. If there is microscopic evidence of disease at or close to the resection margin, postoperative radiation was used to achieve better local control. In cases of undifferentiated carcinoma, preoperative chemotherapy and radiation therapy showed improved outcomes.

• Journal of Life Science
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• v.26 no.9
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• pp.1056-1062
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• 2016

Lung cancer is currently the most common malignant disease and the leading cause of mortality in the world and non-small cell lung cancer (NSCLC) accounts for 75-80% of lung cancer cases. miR-155 gene was found to be over expressed in several solid tumors, such as thyroid carcinoma, breast cancer, colon cancer, cervical cancer, pancreatic ductal adenocarcinoma (PDAC) and lung cancer. The aims of this study were to define the expression of miR-155 in lung cancer and its associated clinic-pathologic characteristics. Total RNA was purified from formalin-fixed, paraffin-embedded NSCLC tissues and benign lung tissues. Expression of miR-155 in human lung cancer tissues were evaluated as mean fold changes of miR-155 in cancer tissues compared to benign lung tissues by quantitative real-time reverse transcriptase polymerase chain reaction (real-time qRT-PCR) and associations of miR-155 expression with clinic-pathologic findings of cancer. Compared with the benign control group, miR-155 expression was significantly overexpressed in NSCLCs (p=<0.001). miR-155 was more overexpressed in squamous cell carcinoma than in adenocarcinoma. Poorly differentiated tumors showed significantly overexpression of miR-155 than well-differentiated tumors (p=<0.001). Overexpression of miR-155 was significantly associated with lymph node metastasis (p=<0.05). In survival analysis for all NSCLC patients, high miR-155 expression was significantly correlated with worse overall survival (p=<0.05). These results suggested that miR-155 might play an important role in lung cancer progression and metastasis.

• Proceedings of the KOR-BRONCHOESO Conference
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• 1981.05a
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• pp.14.2-14
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• 1981

In 1859, Billroth used the term "Zylindrome" to describe a tumor arising in the paranasal sinuses. This neoplasm has been referred to by a variety of terms including cylindroma, basaloma, basaloid adenoma, cribriform adenocarcinoma, and "adenoid cystic carcinoma", now preferred by most authors. It most often arises in the major and minor salivary glands of the head and neck but has been noted in the trachea, lung, breast, skin and elsewhere. The tumors are characterized by a high incidence of local recurrence and ultimate distant metastases after agrressive attempts at surgical excision. Radiation therapy, while not curative, has proved uniformly useful in promoting tumor regression and pain relief as a palliative treatment. The present study was undertaken to review our experience with a group of 44 patients with adenoid cystic carcinoma of the head and neck, diagnosed at the Jeonju Presbyterian Medical Center between 1963 and 1980. The results are as follows: 1. Forty-four cases of adenoid cystic carcinoma represented 40% of the malignant salivary gland tumors during the same interval. 2. The most common primary sites were palate(8 cases) and submandibular gland (8 cases). 3. Thirteen patients (31%) had tumors. that arose in the major salivary glands; 29 (69%), minor salivary glands. 4. Of the 44 patients, there were 21 males. and 23 females. 5. Age at diagnosis ranged from 19 to 78 years; the average age was 50 years. 6. The tumor size was more than 4cm to 6cm in its greatest diamension in 10 patients. Clinically positive cervical lymph nodes were found in 7 patients; distant metastasis in one case at the time of diagnosis. 7. Radical excision was employed in 27 patients, 14 of whom combined with radiotherapy. 8. Of 29 patients available for follow-up the gross and determinate 3-year survival rates were 27.6% and 44.4%, respectively. Among twelve patients who received radical excision, the 3-year survival was 58%. 9. Ten of these 44 patients had local recurrence in an interval of 3 to 88 months. from the initial treatment. Of ten recurrences, 3 occured after 5 years. 10. Distant metastasis was found in 3 of the treated patients. All were pulmonary metastasis.