• Radiation Oncology Journal
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• v.22 no.3
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• pp.192-199
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• 2004

Purpose: To determine the patterns on evaluation and treatment in the patient with early breast cancer treated with conservative surgery and radiotherapy and to improve the radiotherapy techiniques, nationwide survey was peformed. Materials and Methods: A web-based database system for korean Patterns of Care Study (PCS) for 6 common cancers was developed. Two hundreds sixty-one randomly selected records of eligible patients treated between 1998$\~$1999 from 15 hospitals were reviewed. Results: The patients ages ranged from 24 to 85 years(median 45 years). Infiltrating ductal carcinoma was most common histologic type (88.9$\%$) followed by medullary carcinoma (4.2$\%$) and infiltrating lobular carcinoma (1.5$\%$). Pathologic T stage by AJCC was T1 in 59.7$\%$ of the casses, T2 in 29.5$\%$ of the cases, Tis in 8.8$\%$ of the cases. Axillary lymph node dissection was peformed I\in 91.2$\%$ of the cases and 69.7$\%$ were node negative. AJCC stage was 0 in 8.8$\%$ of the cases, stage I in 44.9$\%$ of the cases, stage IIa in 33.3$\%$ of the cases, and stage IIb in 8.4$\%$ of the cases. Estrogen and progesteron receptors were evaluated in 71.6$\%$, and 70.9$\%$ of the patients, respectively. Surgical methods of breast-conserving surgery was excision/lumpectomy in 37.2$\%$, wide excision in 11.5$\%$, quadrantectomy in 23$\%$ and partial mastectomy in 27.5$\%$ of the cases. A pathologically confirmed negative margin was obtained in 90.8$\%$ of the cases. Pathological margin was involved with tumor in 10 patients and margin was close (less than 2 mm) in 10 patients. All the patients except one recieved more than 90$\%$ of the planned radiotherapy dose. Radiotherapy volume was breast only In 88$\%$ of the cases, breast+supraclavicular fossa (SCL) in 5$\%$ of the cases, and breast+ SCL+ posterior axillary boost in 4.2%$\%$of the cases. Only one patient received isolated internal mammary lymph node irradiation. Used radiation beam was Co-60 in 8 cases, 4 MV X-ray in 115 cases, 6 MV X-ray in 125 cases, and 10 MV X-ray in 11 cases. The radiation dose to the whole breast was 45$\~$59.4 Gy (median 50.4) and boost dose was 8$\~$20 Gy (median 10 Gy). The total radiation dose delivered was 50.4$\~$70.4 Gy (median 60.4 Gy). Conclusion: There was no major deviation from current standard in the patterns of evaluation and treatment for the patients with early breast cancer treated with breast conservation method. Some varieties were identified in boost irradiation dose. Separate analysis for the datails of radiotherapy planning will be followed and the outcome of treatment is needed to evaluate the process.

• The Korean Journal of Nuclear Medicine Technology
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• v.14 no.2
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• pp.145-149
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• 2010

Purpose: Recently, $^{18}F$-FDG Fusion PET which has a high sensitivity for diagnosing cancer is being used for purpose of health examination. This study is to demonstrate that $^{18}F$-FDG fusion PET study is useful for diagnosing an early stage cancer. Materials and Methods: This research has been conducted with 2790 patients visited Seoul National University Hospital Healthcare System (SNUHHS) for $^{18}F$-FDG fusion PET study for a health examination from February, 2004 to December 2008. PET/CT images were acquired from skull base to femur after 1 hour from injecting $^{18}F$-FDG 0.14 mCi/kg to the patients. GEMINI GS (Philips, Netherlands) was used for scanning. Results: From February 2004 to December 2008, $^{18}F$-FDG Fusion PET study was performed for 99,009 patients among all patients who visited SNUHHS and 2,790 patients was performed. Diagnostic rate for malignant cancer was 0.95% for the patients who were not examined by $^{18}F$-FDG Fusion PET study. 1.94% was for the patients who were. The rate of malignant tumor was showed 10% and benign tumor was 90% among 542 patients who showed abnormality in the PET/CT images. Types and rates of malignant tumor showed thyroid cancer: 31.5%, lung cancer: 14.8%, stomach cancer: 9.3%, rectum cancer: 3.7%, breast cancer: 3.7%, metastasis cancer: 16.7%. Nonspecific lymph node in the mediastinum, physiologic uptake in the colon, diffuse mild hypermetabolism in bilateral thyroid gland were shown as a benign tumor. Conclusion: The diagnostic rate of malignant tumor with $^{18}F$-FDG Fusion PET for a purpose of health examination was relatively higher than general medical examination. Consequently, it is superior and useful for applying $^{18}F$-FDG Fusion PET study for health examination.

• Journal of Chest Surgery
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• v.40 no.2 s.271
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• pp.114-121
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• 2007

Background: Apoptosis plays a crucial role in carcinogenesis, as well as in development and tissue homeostasis. Terminal deoxyribonucleotidyl transferase mediated neck end labelling (TUNEL) and in situ nick end labelling (ISEL) have been used to investigate the apoptosis in tissues. Since the introduction of the M30 monoclonal antibody to overcome drawbacks of TUNEL and ISEL, the apoptosis in various tumors, with the exception of pulmonary carcinomas, has been studied. In this study, attempts were made to examine the correlation of apoptosis in non-small cell carcinomas, using both M30 and the expression of p53 protein, with the clinicopathological factors. Material and Method: Forty five patients with surgically resected non-small cell carcinomas were included. Immunohistochemical staining with M30 and p53 monoclonal antibody were peformed, and their expressions compared with the clinicopathological features. The overall survival time and recurrence-free survival time were calculated, and the factors influencing the survival time analyzed using a univariate analysis. The effects of the expression stati of M30 and p53 on the risks of cancer related to both death and recurrence were evaluated using a multivariate analysis. Result: The p53 positive group had many more M30 positive cells than the p53 negative group (p53 positive group; $61.7{\pm}26.8$ cells vs. p53 negative group; $45.6{\pm}29.6$ cells, p=0.005) and significantly more p53 positive patients showing at least 10 positive cells (apoptotic index, $Al{\ge}1$) on M30 staining (p53 positive group; 52.4% (11/21) vs. p53 negative group 16,7% (4/24), p=0.025). In the univariate analysis, the survival times in relation to smoking (pack-year), performance status (PS) and Al showed significant differences. The multivariate analysis demonstrated the relative risk (R.R) of cancer death increased almost 7.5-fold (R.R 7.482; 95% Cl $1.886{\sim}29.678$; p=0.004) and the risk of recurrence almost 3,8-fold (R.R 3.795; 95% Cl: $1.184{\sim}12.158$; p=0.025) in the high Al (${\ge}1$) compared to the low Al (<1) group. There was no prognostic effect of p53 expression on the survival time or risk of cancer death and recurrence. Conclusion: In non-small cell lung carcinomas, M30 immunohistochemistry was an excellent method for analyzing apoptosis; the high apoptotic index could be an adverse prognostic predictive factor.

• The Korean Journal of Cytopathology
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• v.7 no.2
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• pp.151-156
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• 1996

Phyllodes tumor(PT) is a rare distinctive fibroepithelial breast tumor that occasionally shows unpredictable clinical behavior. Wide excision should be the primary treatment of PT and enucleation, the standard procedure for fibroadenoma(FA), is proscribed due to high frequency of local recurrence. Therefore an accurate preoperative diagnosis of PT is essential in order to ensure proper surgical treatment. However, the differentiation between benign PT and FA is often difficult on the basis of cytologic findings. In an attempt to better understand the cytologic features of benign PT and possibly to differentiate PT from FA on the findings of fine needle aspiration(FNA) smears, we reviewed cytologic smears from 22 histologically diagnosed cases each of benign PT and FA, respectively. The cytologic features assessed were cellularity and atypia of both epithelial and stromal components, and shape of epithelial cell clusters. Atypia of stromal cells was more frequent in PT, while blunt branching pattern of epithelial cells was more frequent in FA. The specific cytologic diagnosis of PT is not possible in many cases, but the abundance of stromal cells with moderate nuclear atypia in the correct clinical setting such as older age and larger size(>4cm) allows the diagnosis.

• Journal of Life Science
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• v.26 no.12
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• pp.1383-1391
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• 2016

Anti-estrogen drugs such as tamoxifen have been used for treating patients with ER-positive, early breast cancer. However, resistance to anti-estrogen treatment is inevitable in most patients. Breast cancer anti-estrogen resistance-3 (BCAR3) has been identified as the protein responsible for the induction of tamoxifen resistance in estrogen-dependent human breast cancer. We have previously reported that BCAR3 regulates the cell cycle progression and the signaling pathway of EGF and insulin leading to DNA synthesis. In this study, we investigated the functional role of BCAR3 in regulating c-Jun transcription in non-tumorigenic human breast epithelial MCF-12A cells. A transient transfection of BCAR3 increased both the mRNA and protein of c-Jun expression, and stable expression of BCAR3 increased c-Jun protein expression. The overexpression of BCAR3 directly activated the promoter of c-jun, AP-1, and SRE but not that of $NF-{\kappa}B$. Furthermore, single-cell microinjection of BCAR3 expression plasmid in the cell cycle-arrested MCF-12A cells induced c-Jun protein expression, and co-injection of dominant negative mutants of Ras, Rac, and Rho suppressed the transcriptional activity of c-Jun in the presence of BCAR3. Furthermore, stable expression of BCAR3 increased the proliferation of MCF-12A cells. The microinjection of inhibitory materials such as anti-BCAR3 antibody and siRNA BCAR3 inhibited EGF-induced c-Jun expression but did not affect IGF-1 induced upregulation of c-Jun. Taken together, we propose that BCAR3 plays a crucial role in c-Jun protein expression and cell proliferation and that small GTPases (e.g., Ras, Rac, and Rho) are required for the BCAR3-mediated activation of c-Jun expression.

• Radiation Oncology Journal
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• v.22 no.4
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• pp.307-315
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• 2004

Purpose: The purpose of this work was to study the differences of cyclooxygenase (COX-2) expression between Korean and Caucasian patients with early-onset breast carcinoma by immunohistochemistry. The test were analyzed to find a correlation between COX-2 and other biomarkers including HER-2/neu amplification, because we previously reported that a significant difference had been found in the expression of HER-2/neu between the two races. Furthermore, we investigated prognostic significance of COX-2 in korean patients. Materials and Methods: Sixty Korean women who were diagnosed breast carcinoma at 45 years old or younger and 60 Caucasian women with breast carcinoma were selected for this study. The median age of both groups was 37 years and tumor sizes were distributed evenly between the two group. Paraffin embedded blocks of primary tumor were processed for immunohistochemical staining of COX-2. The COX-2 expression was evaluated according to the percentage of positive cells and the intensity of staining. And the results were compared with the data of the previous studies to find correlation between COX-2 and other parameters and survival data. Results: Proportion of the COX-2 expression in total patients was $27.6\%$. The percentage of tumors that stained positive for COX-2 in korean and Caucasian women with early-onset breast carcinoma were $37.9\%$ and $20.8\%$, respectively. The difference was statistically not significant(p=0.090). Expression of COX-2 was not associated with several clinicopathologic parameters including HER-2/neu overexpression, but negative estrogen receptor status was correlated with significance (p=0.046). The 5 year disease free survival rate for patients with COX-2 expression was $67.9\%$, compared to $81.9\%$ of the COX-2 negative patients and the result was statistically not significant. Conclusions : A significant difference was not found in the expression of COX-2 between the two groups of patients with early-onset breast carcinoma. And correlation between COX-2 and other parameters was not observed except estrogen receptor negativity. Large scaled further research including radiotherapy factors will be needed to identify COX-2 as a prognostic role in patients with early-onset breast carcinoma.

• Nuclear Medicine and Molecular Imaging
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• v.43 no.6
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• pp.565-571
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• 2009

Purpose: The aim of this study was to evaluate the clinical value of rectal gas distension F-18 FDG PET/CT imaging for the differentiation of the rectal focal uptake lesions. Materials and Methods: Twenty four patients (M:F=11:13, Age $62.8{\pm}12.4$ years) underwent rectal gas distension F-18 FDG PET/CT, prospectively: initial image at 50-60 min after the intravenous injection of F-18 FDG and rectal distension image after the infusion of air through the anus. Focally increased uptake lesions on initial images but disappeared on rectal distension images defined a physiological uptake. For the differential evaluation of persistent focal uptake lesions on rectal distension images, colonoscopy and histopathologic examination were performed. Results: Among the 24 patients, 27 lesions of focal rectal uptake were detected on initial images of F-18 FDG PET/CT. Of these, 7 lesions were able to judge with physiological uptake because the focal increased uptake disappeared from rectal distension image. Remaining 3 lesions were non-rectal lesions (2 lesions: rectovesical space, 1 lesion: uterine myoma). Among 17 lesions which was showed persistent increased uptake in rectal distension image, 15 lesions were confirmed as the malignant tumor (SUVmax=$15.9{\pm}6.8$) and 2 lesions were confirmed as the benign lesions including adenoma and inflammatory disease. Conclusion: The rectal distension F-18 FDG PET/CT imaging could be an important noninvasive method for the differentiation of malignant and benign focal rectal uptake lesions including physiologic uptake.

• Journal of Chest Surgery
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• v.31 no.3
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• pp.266-270
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• 1998

The management of malignant pleural effusion is a difficult problem. Tetracycline was probably the most commonly used sclerosing agent, but parenteral tetracycline is no longer available. This prospective study was designed to determine the efficacy of insufflated talc in producing plerodesisin patients with malignant pleural effusions. Fifteen patients managed between March 1995 and March 1997 underwent thoracoscopy and had 4 gm sterile asbestos-free talc insufflation throughout the pleural space. The mean interval between the procedure and last follow-up was 101 days(range: 25-233 days). The results of treatment were clinically and radiologically compared with pre-operative status. The results were as follows: 1. The patients were 6 men and 9 women with a mean age of 55.1 years(range: 31-74 years). The primary tumors were lung cancer in 10 patients, breast cancer in two, hepatoma in one, stomach cancer in one, and adenocarcinoma of unkown origin in one. 2. Cancer cell positive ratio was 36% in sputum cytology study and 100% in thoracoscopic biopsy. 3. Symptoms improved in 94% of patients treated by talc pleurodesis. 4. After 30 days of the procedure, there was radiologically no recurrence of plural fluid in 94% patients. 5. There were wound infection in one, respiratory failure in one. In conclusion, the insufflation of 4 gm sterile asbestos-free talc in the pleural space is an effective method to control malignant pleural effusions and patients selection is important factor for reexpansion the lung.

• The Korean Journal of Cytopathology
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• v.10 no.1
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• pp.27-34
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• 1999

Benign and malignant papillary neoplasms of the breast may be difficult to distinguish in both cytologic and histologic preparations. To define the cytologic features of benign and malignant papillary lesions, we retrospectively reviewed 18 cases of fine needle aspirates from histologically confirmed cases of papilloma or papillary carcinoma of the breast. This study included 3 intraductal papillary carcinomas, 3 invasive papillary carcinomas, and 12 intraductal papillomas. Ail cases were evaluated for presence or absence of papillary fragments, bloody background, apocrine metaplasia, macrophages, and degree of cellularity, atypia, and single isolated columnar epithelial cells. Papillary fragments were present in all cases. The background of the smear was bloody in all 6 carcinomas, but in only 7 out of 12 papillomas. Markedly increased cellularity was present in 4 carcinomas(67%) and 7 papillomas(58%). Single cells were present in 5 carcinomas(83%) and 8 papillomas(67%). The majority of papillomas and papillary carcinomas had mild to moderate atypia, and severe atypia was noted in one case of intraductal papillary carcinoma and one case of invasive papillary carcinoma. Apocrine metaplasia was absent in all cases of papillary carcinomas, but present in 8 papillomas(57%). Macrophages were noted in 4 carcinomas and were present in all cases of papillomas. The constellation of severe atypia, bloody background, absence of apocrine metaplasia and/or macrophages were features to favor carcinoma. Malignant lesions tended to show higher cellularity and more single isolated cells. The cytologic features mentioned above would be helpful to distinguish benign from malignant papillary lesions of the breast. However, because of overlapping of cytologic features, surgical excision should be warranted in all cases on papillary lesions of the breast to further characterize the tumor.

• Tuberculosis and Respiratory Diseases
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• v.41 no.4
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• pp.339-353
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• 1994

Background : The p53 gene codes for a DNA-binding nuclear phosphoprotein that appears to inhibit the progression of cells from the G1 to the S phase of the cell cycle. Mutations of the p53 gene are common in a wide variety of human cancers, including lung cancer. In lung cancers, point mutations of the p53 gene have been found in all histological types including approximately 45% of resected NSCLC and even more frequently in SCLC specimens. Mutant forms of the p53 protein have transforming activity and interfere with the cell-cycle regulatory function of the wild-type protein. The majority of p53 gene mutations produce proteins with altered conformation and prolonged half life; these mutant proteins accumulate in the cell nucleus and can be detected by immunohistochemical staining. But protein overexpression has been reported in the absence of mutation. p53 protein overexpression or gene mutation is reported poor prognostic factor in breast cancer, but in lung cancer, its prognostic significance is controversial. Method : We investigated the p53 abnormalities by nucleotide sequencing, polymerase chain reaction-single strand conformation polymorphism(PCR-SSCP), and immunohistochemical staining. We correlated these results with each other and survival in 75 patients with NSCLC resected with curative intent. Overexpression of the p53 protein was studied immunohistochemically in archival paraffin- embedded tumor samples using the D07(Novocastra, U.K.) antibody. Overexpression of p53 protein was defined by the nuclear staining of greater than 25% immunopositive cells in tumors. Detection of p53 gene mutation was done by PCR-SSCP and nucleotide sequencing from the exon 5-9 of p53 gene. Result: 1) Of the 75 patients, 36%(27/75) showed p53 overexpression by immunohistochemical stain. There was no survival difference between positive and negative p53 immunostaining(overall median survival of 26 months, disease free median survival of 13 months in both groups). 2) By PCR-SSCP, 27.6%(16/58) of the patients showed mobility shift. There was no significant difference in survival according to mobility shift(overall median survival of 27 in patients without mobility shift vs 20 months in patients with mobility shift, disease free median survival of 8 months vs 10 months respectively). 3) Nucleotide sequence was analysed from 29 patients, and 34.5%(10/29) had mutant p53 sequence. Patients with the presence of gene mutations showed tendency to shortened survival compared with the patients with no mutation(overall median survival of 22 vs 27 months, disease free median survival of 10 vs 20 months), but there was no statistical significance. 4) The sensitivity and specificity of immunostain based on PCR-SSCP was 67.0%, 74.0%, and that of the PCR-SSCP based on the nucleotide sequencing was 91.8%, 96.2% respectively. The concordance rate between the immunostain and PCR-SSCP was 62.5%, and the rate between the PCR-SSCP and nucleotide sequencing was 95.3%. Conclusion : In terms of detection of p53 gene mutation, PCR-SSCP was superior to immunostaining. p53 gene abnormalities either overexpression or mutation were not a significant prognostic factor in NSCLC patients resected with curative intent. However, patients with the mutated p53 gene showed the trends of early relapse.