• Tuberculosis and Respiratory Diseases
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• v.44 no.4
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• pp.796-805
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• 1997

Background : It is clear that deregulation of cell cycle progression is a hallmark of neoplastic transformation and genes involved in the $G_1$/S transition of the cell cycle are especially frequent targets for mutations in human cancers, including lung cancer. p16 gene product, one of the G1 cell-cycle related proteins, that is recently identified plays an important role in the negative regulation of the the kinase activity of the cyclin dependent kinase (cdk) enzymes. Therefore p16 gene is known to be an important tumor suppressor gene and is also called MTS1 (multiple tumor suppressor 1). No more oncogenes have been reported to be frequently related to multiple different malignancies than the alterations of p16 gene. Especially when it comes to non-small cell lung cancer, there was no expression of p16 in more than 70% of cell lines examined. And also it is speculated that p16 gene could exert a key role in the development of non-small cell lung cancer. This study was designed to evaluate whether p16 gene could be used as a candidate for gene therapy of non-small cell lung cancer. Methods : After the extraction of total RNA from normal fibroblast cell line and subsequent reverse transcriptase reaction and polymerase chain reaction, the amplified p16 cDNA was subcloned into eukaryotic expression plasmid vector, pRC-CMV. The constructed pRC-CMV-p16 was transfected into the NCI-H441 NSCLC cell line using lipofectin. The changes of G1 cell-cycle related proteins were investigated with Western blot analysis and immunoprecipitation after extraction of proteins from cell lysates and tumor suppressive effect was observed by clonogenic assay. Results : (1) p16(-) NCI-H441 cell line transfected with pRC-CMV-p16 showed the formation of p16 : cdk 4 complex and decreased phosphorylated Rb protein, while control cell line did not. (2) Clonogenic assay demonstrated that the number of colony formation was markedly decreased in p16(-) NCI-H441 cell line transfected with pRC-CMV-p16 than the control cell line. Conclusion : It is confirmed that the expression of p16 protein in p16 absent NSCLC cell line with the gene transfection leads to p16 : cdk4 complex formation, subsequent decrease of phosphorylated pRb protein and ultimately tumor suppressive effects. And also it provides the foundation for the application of p16 gene as a important candidate for the gene therapy of NSCLC.

• Tuberculosis and Respiratory Diseases
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• v.44 no.4
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• pp.766-775
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• 1997

Background : Primary malignant tumors of the trachea are extremely rare entities and account for a mere 0.1 per cent of all malignancies of the respiratory tract. Because of vague localizing signs, symptoms and a usually negative routine chest film, the patients with tracheal tumors are often treated for asthma or chronic obstructive pulmonary disease for considerable period of time before correct diagnosis. Method : We have made a review of the 17 cases of primary tracheal tumors in recent 15 years. We reviewed the clinical features including history of smoking and respiratory symptoms, the official readings of initial routine chest film, the cytologic examination of sputum, the time of delay in diagnosis, and the response according to the therapeutic modalities. Results : Eight out of 9 patients with squamous cell carcinoma(SCC) were above 50 years old, five out of 6 patients with adenoid cystic carcinoma(ACC) were below 50 years old. The most common location of primary tracheal tumors was the upper one-third of trachea in 8 cases(47%). The most frequent symptoms were dyspnea in 13/17 cases(76%) and then stridor or wheezing, cough. and sputum in order. The routine chest roentgenographic examinations were not helpful to diagnose tracheal carcinoma and the cytologic examinations of sputums were helpful to diagnose tracheal carcinoma in only one case with adenocarcinoma. The mean times of delay in diagnosis of patients with sec and ACC were 5 months and 24.9 months respectively. We had bronchial asthma in 8 cases(47%) and tracheal tumors in 4 cases(23%) as initial clinical impression. Conclusion : We would like to perform more comprehensive diagnostic tools(high KVP technique, the fibroptic bronchoscopic examination, chest CT scan etc.) in patients who had the suggestive points for the tracheal tumorse(1. unexplained hemoptysis or hoarsness, 2. inspiratory wheezing or stridor, 3. wax and waning of dyspnea according to changes of position, 4. progressive asthmatics unresponsive to antiasthmatic therapy) and radical resection of tumor or external radiation therapy with curative aim as possible.

• The Korean Journal of Nuclear Medicine
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• v.39 no.6
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• pp.456-463
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• 2005

Purpose: we often find variable degrees of FDG uptake and patterns in stomach, which can make difficult to distinguish physiologic uptake from pathologic uptake on FDG PET. The purpose of this study was to find out the significant findings of stomach on FDG PET. Materials and Methods: Thirty-eight patients who underwent both FDG PET and endoscopy within one week from Jun. 2003, to Aug. 2004 were included in this study. We reviewed 38 patients (18 for medical check up, 15 for work up of other malignancies, and 5 for the evaluation of stomach lesion). Their mean age was 56 years old (range:$32{\sim}79$), men and women were 28 and 10, respectively. Two nuclear physicians evaluated five parameters on FDG PET findings of stomach with a consensus: 1) visual grades 2) maximum SUV (max.SUV) 3) focal 4) diffuse and S) asymmetric patterns. We correlated the lesions of FDG PET findings of stomach with those of endoscopy. We considered more than equivocal findings on FDG PET as positive. Results: The six of 38 patients were proven as malignant lesions by endoscopic biopsy and others were inflammatory lesions (ulcer in 3, chronic atrophic gastritis in 12, uncommon forms of gastritis in 5), non-inflammatory lesions (n=3), and normal stomach (n=9). By the visual analysis, malignant lesions had higher FDG uptake than the others. The max.SUV of malignant lesions was $7.95{\pm}4.83$ which was significantly higher than the other benign lesions ($2.9{\pm}0.69$ in ulcer, $3.08{\pm}1.2$ in chronic atrophic gastritis, $3.2{\pm}1.49$ in uncommon forms of gastritis (p=0.044)). In the appearance of stomach on FDG PET, malignant lesions were shown focal (5 of 6) and benign inflammatory lesions were shown diffuse (9 of 20) and asymmetric (14 of 20). Benign lesions and normal stomach were shown variable degrees of uptake and patterns. Some cases of benign inflammatory lesions such as ulcer and gastritis were shown focal and mimicked cancerous lesion (4 of 15). Conclusion: Gastric malignant lesions had higher FDG uptake and focal pattern. However, benign inflammatory lesions had moderate degrees of uptake and diffuse and asymmetric patterns rather than focal. It is difficult to differentiate between benign lesions including normal.

• The Korean Journal of Nuclear Medicine
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• v.35 no.5
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• pp.301-312
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• 2001

Purpose: Stomach cancer is one of the most common malignancies in Korea, but there is no report on FDG PET in patients with stomach cancer. We observed findings of FDG PET in patients with stomach cancer. Materials and Methods: In 13 patients with pre-operative stomach cancer, PET and CT were performed. Primary lesion and regional lymph nodes detection were aualyzed. Correlation between FDG uptake ratio and each prognostic factor of primary lesion was analyzed. In 19 patients diagnosed as recurrence or displaying suspicious symptoms, conventional work up including tumor marker and PET were performed. Recurrence detection of anastomotic site, distant metastasis, and tumor marker elevation were analyzed. Results: Sensitivity for primary lesion detection was 83.3% (CT 71.4%) and two submucosal lesions were undetected. FDG uptake ratio was variable and had no correlation with invasion-depth, size, Borrmann type, staging and differentiation. Sensitivity for regional lymph node detection was 58.3% (CT 58.3%) and the lesions less than 1cm were undetected. Sensitivity for recurrence detection was 100% but there were three false positives. Sensitivity for distant metastasis detection was 64.3% and significantly higher than that of conventional work-up (21.4%). Average of tumor marker level in patients who were confirmed as recurrence was higher than false positive. Conclusion: PET is more useful than conventional work up in distant metastasis detection when recurrence is suspected. In pre-operative stomach cancer, PET is comparable to CT for detection of primary lesion and regional lymph node metastasis and detection of distant metastasis requires further study.

• Korean Journal of Head & Neck Oncology
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• v.9 no.1
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• pp.25-32
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• 1993

The nodular hyperplasia of the thyroid is a common thyriod disease. Nodular hyperplasia does rarely progress to thyroid cancer. The differentiation of a nodular hyperplasia from a neoplasm may be simple or difficult, both clinically and anatomically. The papillary carcinoma of the thyroid is the most common type of thyroid malignancies. There were few studies about cytogenetic observation in thyroid cancer. But only one case of banding observation in nodular hyperplasia have been reported. In order to compare the chromosomal changes in the thyroid cancer and the noncancerous thyroid disease, we performed cytogenetic analysis in two papillary carcinoma and two nodular hyperplasia after cell culture. The chromosomal pattern of the nodular hyperplasia found was very heterogenous but no clonal abnormaly in both cases was observed. Case I : A modal chromosomal number was in 42-46 range. Chromosome 8, 19, 21. 22 were commonly lost. 9 structural anomalities among 51 analysed cells were observed but they were not clonal. Case II: A modal chromosomal number was 43. Chromosome 17 and 19 were commonly lossed. Common cytogenetic characters of this two nodular hyperplasia are hypodiploidity and very heterogenous chromosomal pattern. The result about the papillary carcinoma are as follow. In one case some numerical and structural chromosomal changes were observed. But they were not clonal abnormality. In another case the chromosomal pattern found was very heterogenous with a clonal abnormality of del(11)(q23). The modal number was 46. The del(11)(q23) a chromosomal change in papillary carcinoma of the thyroid have previously been reported(Eva Olah et al. 1989). We suggest that 11q deletion may be important role to pathogenesis of papillary carcinoma of the thyroid. According to this results, we could not find out specific differences about chromosomal changes and any relationship between the papillary carcinoma and the nodular hyperplasia.

• Radiation Oncology Journal
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• v.20 no.1
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• pp.17-23
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• 2002

Purpose : To clarify the clinical benefit derived from the combined modality therapy (CMT) consisting of chemotherapy (CT) and involved field radiotherapy (RT) for stage I and II angiocentric lymphomas of the head and neck. Materials and Methods : Of 143 patients with angiocentric lymphoma of the head and neck treated at our hospital between 1976 and 1995, 104 patients (RT group) received involved field RT alone with a median dose of 50.4 Gy (range : 20~70 Gy), while 39 patients (CMT group) received a median 3 cycles (range : 1~6 cycles) of CT before involved field RT. The response rate, patterns of failure, complications, and survival data of the RT group were compared with those of the CMT group. Results : Despite a higher response rate, local failure was the most common pattern of failure in patients of both groups. The patterns of failure, including the systemic relapse rate were not influenced by the addition of combination CT. Although both modalities were well tolerated by the majority of patients, aberrant immunologic disorders or medical illnesses, such as a hemophagocytic syndrome, sepsis, intractable hemorrhage, or the evolution of second primary malignancies were more frequently observed in patients of the CMT group. The prognosis of patients in the RT group was relatively poor, with a 5-year overall actuarial survival rate of 38% and disease-free survival rate of 32%, respectively. However, their clinical outcome was not altered by the addition of systemic CT. Achieving complete remission was the most important prognostic factor by univariate and multivariate analyses, but treatment modality was not found to be a prognostic variable influencing survival. Conclusions : Involved field RT alone for angiocentric lymphoma of the head and neck was insufficient to achieve an improved survival rate, but the addition of CT to involved field RT failed to demonstrate any therapeutic advantage over involved field RT alone.

• The Journal of the Korean bone and joint tumor society
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• v.15 no.2
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• pp.111-121
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• 2009

Background: Osteosarcoma is one of the most common primary malignant tumors of bone occurring mainly in children and adolescents. Although surgery combined with chemotherapy has markedly improved patient survival during the last years, the use of anticancer drugs is still associated with serious problem, such as the frequent acquisition of drug-resistant phenotypes and occurrence of "secondary malignancies". Several solid tumors display enhanced expression of matrix metalloproteinases (MMPs), and recently clinical trials have been initiated on MMP-inhibitors. On the other hand, bisphosphonates (BPs) are inhibitors of bone resorption, and widely used to treat osteoclast-mediated bone diseases. Also they appear to possess direct antitumor activity. Methods: One osteosarcoma cell line (U2OS) was treated with ibandronate (0, 0.1, 1, $10{\mu}M$) for 48 hours. Cell viabilities were determined using MTT assay, the mRNA levels of MMP-2 and MT1-MMP were detected by reverse-transcription polymerase chain reaction, the amount of MMP-2 and MT1-MMP protein were measured by Westernblot, the activities of MMP-2 were observed by Gelatin zymography, and Matrigel invasion assays were used to investigate the invasive potential of osteosarcoma cell lines before and after ibandronate treatment. Results: The invasiveness of U2OS cell line was reduced dose-dependently following 48 hour treatment of up to $10{\mu}M$ of the ibandronate at which concentration no cytotoxicity occurred. Furthermore, the gelatinolytic activities and protein and mRNA levels of MMP-2 and MT1-MMP were also suppressed by increasing ibandronate concentrations. Conclusion: Given that MMP-2 is instrumental in tumor cell invasion, it is very likely that the reduction in osteosarcoma cell invasion by ibandronate is a consequence, at least in part, of suppressed expression of both MMP-2 and MT1-MMP. Isolation of a molecule (s) responsible for the bisphosphonate inhibition of tumor cell invasion would pave the way for the development of a new generation of metastasis inhibitors.

• The Journal of the Korean bone and joint tumor society
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• v.9 no.1
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• pp.1-11
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• 2003

Purpose: To analysis of the result of the treatment of metastatic diaphyseal fracture of the humerus with closed interlocking intrameduallry nailing. Materials and Methods: Among surgically treated 29 patients with pathologic or impending fracture of diaphysis of the humeurs, 13 patients (16 cases) treated with closed intramedullary interlocking nail were selected for the study. The final result of pain relief and functional recovery was evaluated by modified rating system of Perez et al. Results: Primary cancer was diagnosed after fracture was developed in 2 patients and pathologic or impending fracture was occurred average period of 28.9 months after primary cancer was diagnosed. The main primary malignancies were multiple myeloma, lung cancer and breast cancer. Mean survival after humeral metastasis was 11.7 months. The final result was superior to fair in 13 of 16 cases, and poor in 3 cases with progression of tumor spread or distant dissemination to the ipsilateral fingers. Except the latter 3 patients and other 3 patients, who died before 3 months postoperatively, bony union was achieved in 10 cases. There were no complications related to surgery. Conclusion: Closed interlocking intrameduallry nailing is accomplished with brief operative time, small amount of bleeding and provides immediate stability with resultant early return of function to the arm. Additionally it allows early postoperative irradiation. However, some of our cases shows that intramedullary nailing can accelerate tumor spread and metastases elsewhere, so that serious consideration must be given in planning this treatment. In conclusion, the functional status before fracture, life expectancy, type of tumor and extent of involvement should be carefully considered to decide operative treatment of metastatic disease.

• Pediatric Infection and Vaccine
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• v.18 no.1
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• pp.40-47
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• 2011

Purpose : Norovirus infection, a common cause of community-acquired gastroenteritis, can also lead to severe illness in immunocompromised patients. We investigated clinical manifestations of norovirus infection in pediatric cancer patients. Methods : Stool specimens were collected from pediatric patients with gastrointestinal symptoms between November 2008 and September 2009 at Samsung Medical Center, Seoul, Korea. Norovirus infection was identified by reverse-transcription polymerase chain reaction (RT-PCR). A retrospective chart review was performed in pediatric cancer patients who were diagnosed with norovirus infection. Results : Ten patients were diagnosed with norovirus infection by RT-PCR in stool samples. The median age was 0.83 years (range 0.25-5.5 years) and the male to female ratio was 1.5:1 (6 males and 4 females). Underlying diseases were hematologic malignancies (4/10, 40%), neuroblastoma (4/10, 40%), and brain tumors (2/10, 20%). Three patients were infected before hematopoietic cell transplantation (HCT) and four patients after HCT. All patients had diarrhea (10/10, 100%), with a median frequency of diarrhea of 8.5 times/day (range 4-22 times/day). Median virus shedding duration was 72.5 days (range 19-299 days). Four patients with pneumatosis intestinalis were conservatively treated with bowel rest and total parenteral nutrition. One patient with severe diarrhea and bloody stool had concomitant chronic gut graft-versus-host disease (GVHD). Norovirus infection-related mortality was not observed. Conclusion : Norovirus infection can cause significant clinical manifestations with prolonged viral shedding in immunocompromised patients. Norovirus should be considered in pediatric cancer patients with severe gastrointestinal symptoms.

• Pediatric Infection and Vaccine
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• v.22 no.2
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• pp.75-80
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• 2015

Purpose: Ventilator-associated pneumonia (VAP) is a serious threat in critically ill pediatric patients. Data regarding Stenotrophomonas maltophilia VAP in pediatric population is limited. We evaluated the clinical data of S. maltophilia associated VAP in critically ill pediatric patients. Methods: A retrospective chart review was performed in pediatric patients 18 years old or younger who developed S. maltophilia associated VAP at Samsung Medical Center, Seoul Korea from January 2008 to December 2012. Results: A total of 31 patients were identified S. maltophilia associated VAP. Median age was 8 months (range, 0.5 month to 16.6 years) and 13 patients were male (40.6%). Underlying illnesses were cardiologic diseases (n=11, 34.4%), hematologic oncologic malignancies (n=7, 25%), neurologic diseases (n=4, 12.5%), pulmonary diseases (n=3, 9.4%), and others (n=4, 12.5%). The median duration of ventilator use before S. maltophilia VAP diagnosis was 14 days (range, 4-256 days). Overall mortality at 30 days was 12.5% (4/32). Conclusions: S. maltophilia should be also considered as a possible pathogen for VAP in critically ill pediatric patients. Empiric antibiotic choice should include agents that are active against S. maltophilia in patients who are deteriorating on broad spectrum beta-lactam antimicrobial agents.