• Journal of Chest Surgery
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• v.43 no.6
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• pp.588-595
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• 2010

Background: Base on types of tumor, the types of expressed tumor is diverse and the difference in its expression rate is even more various. Due to such reasons an animal model is absolutely needed for a clinical research of lung cancer. The author attempted oncogenesis by cultivating a cell line of non-small cell carcinoma and then injecting it inside thoracic cavities of nude mice. The author conducted quantitative analyses of HER2/neu tumor gene - an epidermal growth factor receptor (EGFR) related to lung cancer, and TGF-${\beta}_1$, which acts as a resistance to cell growth inhibition and malignant degeneration. In order to investigate achievability of the oncogenesis, histological changes and the expression of cancer gene in case of orthotopic lung cancer is necessary. Material and Method: Among 20 immunity-free male BALB/c, five nude mice were selected as the control group and rest as the experimental group. Their weights ranged from 20 to 25 gm (Orient, Japan). After injection of lung cancer line (SW900 G IV) into the pleural cavity of nude mice, They were raised at aseptic room for 8 weeks. HER2/neu was quantitatively analyzed by separating serum from gathered blood via chemiluminiscent immunoassay (CLIA), and immunosandwitch method was applied to quantitatively analyze TGF-${\beta}_1$. SPSS statistical program (SPSS Version 10.0, USA) was implemented for statistical analysis. Student T test was done, and cases in which p-value is less than 0.05 were considered significant. Result: Even after lung cancer was formed in the normal control group or after intentionally injected lung cancer cell line, no amplification of HER2/neu gene showed reaction. However, the exact quantity of TGF-${\beta}_1$ was $28,490{\pm}8,549pg/mL$, and the quantity in the group injected with lung cancer cell was $42,362{\pm}14,449pg/mL$, meaning 1.48 times highly Significant (p<0.483). It proved that HER2/neu gene TGF-${\beta}_1$ had no meaningful interconnection. Conclusion: TGF-${\beta}_1$ gene expressed approximately 1.48 times amplification in comparison to the control group. The amplification of TGF-${\beta}_1$ meant somatic recuperation inhibition mechanism due to carcinogenesis in nude mice was definitely working. It may be implemented as a quantitative analysis that allows early detection of lung cancer in human body.

• Tuberculosis and Respiratory Diseases
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• v.41 no.5
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• pp.452-461
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• 1994

Background: Tumor necrosis factor(TNF)-$\alpha$ and Interleukin(lL)-$1{\beta}$ are thought to play a major role in the pathogenesis of the septic syndrome, which is frequently associated with adult respiratory distress syndrome(ARDS). In spite of many reports for the role of TNF-$\alpha$ in the pathogenesis of ARDS, including human studies, it has been reported that TNF-$\alpha$ is not sensitive and specific marker for impending ARDS. But there is a possibility that the results were affected by the diversity of pathogenetic mechanisms leading to the ARDS because of various underlying disorders of the study group in the previous reports. The purpose of the present study was to evaluate the roles of TNF-$\alpha$ and IL-$1{\beta}$ as a predictable marker for development of ARDS in the patients with septic syndrome, in which the pathogenesis is believed to be mainly cytokine-mediated. Methods: Thirty-six patients of the septic syndrome hospitalized in the intensive care units of the Asan Medical Center were studied. Sixteens suffered from ARDS, whereas the remaining 20 were at the risk of developing ARDS(acute hypoxemic respiratory failure, AHRF). In all patients venous blood samples were collected in heparin-coated tubes at the time of enrollment, at 24 and 72 h thereafter. TNF-$\alpha$ and IL-$1{\beta}$ was measured by an enzyme-linked immunosorbent assay (ELISA). All data are expressed as median with interquartile range. Results: 1) Plama TNF-$\alpha$ levels: Plasma TNF-$\beta$ levels were less than 10pg/mL, which is lowest detection value of the kit used in this study within the range of the $mean{\pm}2SD$, in all of the normal controls, 8 of 16 subjects of ARDS and in 8 in 20 subjects of AHRF. Plasma TNF-$\alpha$ levels from patients with ARDS were 10.26pg/mL(median; <10-16.99pg/mL, interquartile range) and not different from those of patients at AHRF(10.82, <10-20.38pg/mL). There was also no significant difference between pre-ARDS(<10, <10-15.32pg/mL) and ARDS(<10, <10-10.22pg/mL). TNF-$\alpha$ levels were significantly greater in the patients with shock than the patients without shock(12.53pg/mL vs. <10pg/mL) (p<0.01). There was no statistical significance between survivors(<10, <10-12.92pg/mL) and nonsurvivors(11.80, <10-20.8pg/mL) (P=0.28) in the plasma TNF-$\alpha$ levels. 2) Plasma IL-$1{\beta}$ levels: Plasma IL-$1{\beta}$ levels were less than 0.3ng/mL, which is the lowest detection value of the kit used in this study, in one of each patients group. There was no significant difference in IL-$1{\beta}$ levels of the ARDS(2.22, 1.37-8.01ng/mL) and of the AHRF(2.13, 0.83-5.29ng/mL). There was also no significant difference between pre-ARDS(2.53, <0.3-8.34ngfmL) and ARDS(5.35, 0.66-11.51ng/mL), and between patients with septic shock and patients without shock (2.51, 1.28-8.34 vs 1.46, 0.15-2.13ng/mL). Plasma IL-$1{\beta}$ levels were significantly different between survivors(1.37, 0.4-2.36ng/mL) and nonsurvivors(2.84, 1.46-8.34ng/mL). Conclusion: Plasma TNF-$\alpha$ and IL-$1{\beta}$ level are not a predictable marker for development of ARDS. But TNF-$\alpha$ is a marker for shock in septic syndrome. These result could not exclude a possibility of pathophysiologic roles of TNF-$\alpha$ and IL-$1{\beta}$ in acute lung injury because these cytokine could be locally produced and exert its effects within the lungs.

• Tuberculosis and Respiratory Diseases
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• v.47 no.5
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• pp.642-649
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• 1999

Background: It is very important to determine an accurate staging of the non-small cell lung cancer(NSCLC) for an assessment of operability and it's prognosis. However, it is difficult to evaluate tumor involvement of mediastinal lymph nodes accurately utilizing noninvasive imaging modalities. PET is one of the sensitive and specific imaging modality. Unfortunately PET is limited use because of prohibitive cost involved with it's operation. Recently hybrid SPECT/PET(single photon emission computed tomography/positron emission tomography) camera based PET imaging was introduced with relatively low cost. We evaluated the usefulness of coincidence detection(CoDe) PET in the detection of metastasis to the mediastinal lymph nodes in patients with NSCLC. Methods: Twenty one patients with NSCLC were evaluated by CT or MRI and they were considered operable. CoDe PET was performed in all 21 patients prior to surgery. Tomographic slices of axial, coronal and sagittal planes were visually analysed. At surgery, mediastinal lymph nodes were removed and histological diagnosis was performed. CoDe PET findings were correlated with histological findings. Results: Twenty of 21 primary tumor masses were detected by the CoDe PET. Thirteen of 21 patients was correctly diagnosed mediastinal lymph node metastasis by the CoDe PET. Pathological N0 was 14 cases and the specificity of N0 of CoDe PET was 64.3%. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of N1 node was 83.3%, 73.3%, 55.6%, 91.7%, and 76.2% respectively. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of N2 node was 60.0%, 87.5%, 60.0%,87.5%, and 90.0% respectively. There were 3 false negative cases but the size of the 3 nodes were less than 1cm. The size of true positive nodes were 1.1cm, 1.0cm, 0.5cm respectively. There were 1 false positive among the 12 lymph nodes which were larger than 1cm. False positive cases consisted of 1 tuberculosis case, 1 pneumoconiosis case and 1 anthracosis case. Conclusion: CoDe PET has relatively high negative predictive value in the enlarged lymph node in staging of mediastinal nodes in patients with NSCLC. Therefore CoDe PET is useful in ruling out metastasis of enlarged N3 nodes. However, further study is needed including more number of patients in the future.

• Tuberculosis and Respiratory Diseases
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• v.56 no.5
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• pp.505-513
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• 2004

Background : In lung cancer patients, the presence of metastatic neck nodes is a crucial indicator of inoperabilty. So thorough physical examination of neck is always mandatory, but sometimes those are hardly palpable even by the skillful hand. Ultrasonography is a useful diagnostic method in detection of small impalpable lymph nodes and in guidance of fine needle aspiration biopsy. In this study we evaluated the clinical usefulness of ultrasonography(USG) and ultrasound-guided fine needle aspiration cytology(US-FNA) in lung cancer patients without palpable neck nodes. Methods and Materials : From Sep 2002 to Sep 2003, 36 non-small cell lung cancer patients (20 adenocarcinoma, 16 squamous cell cancer) and 10 small cell lung cancer patients without palpable neck nodes on physical examiation were enrolled. patients who had contralateral mediastinal nodal enlargement(>1cm) on chest CT were excluded. After the routine check of USG on the neck, US-FNA was done in cases with enlarged neck nodes (${\geq}5mm$ in the short axis). The presence of enlarged lymph node on USG, and of malignant cells on cytology were evaluated by the histological type and the patients' clinical stage of lung cancer. Results : Among 36 non-small lung cell cancer patients, 14 (38.8%) had enlarged neck nodes on USG, and 5 of 10 small cell lung carcinoma patients. The mean diameter of the neck nodes was 9.8 mm (range, 7-12 mm). US-FNA of 14 non-small cell lung cancer patients revealed tumor cells in eight patients (57.1%). In 5 small cell lung cancer pateints, tumor cells were found in all cases. By the result of US-FNA, the clinical stage of 8 out of 36 (22.2%) non-small cell lung cancer patients had changed, including two cases of shift from the operable IIIa to the inoperable IIIb. In small cell lung cancer patients their clinical stage was not changed after US-FNA, but their pathological diagnosis was easily done in two cases, in whom endobronchial lesions were not found on bronchoscopy. Conclusions : USG and US-FNA of neck node seem to be safe, sensitive and cost-effective diagnostic tools in the evaluation of lung cancer patients without palpable neck nodes.

• The Journal of the Korean bone and joint tumor society
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• v.7 no.1
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• pp.13-19
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• 2001

Background : The incidence of malignant melanoma is currently increasing at a rate greater than any other cancer occuring in human. At this time, early diagnosis and surgical excision were the mainstay of treatment for patients with malignant melanoma. We reviewed the results of average 4 years of follow-up after surgical excision of total 16 cases of malignant melanoma since 1985. Materials and Methods : There were 16 patients (mean age 58.5 years, 5 men, 11 women). The site of the primary lesion was foot and toe (6), back (3), hand (2), thigh (2), shoulder (1), lower abdomen (1) and lip (1). The lymph node was involved at 9 patients. The histologic diagnosis was made with H-E, S-100 stain, and HMB-45 stain as a special stain. Results : Histologically, there were Clark's stage I for 3 patients, II in 4, III in 2, IV in 3, and stage V in 4 patients. The wide excision only greater than 2cm margin was performed for 4 patients. The wide excision and lymph node dissection were performed for 4 patients. The amputation was only performed for 3 patients, and the amputation and lymph node dissection were performed for 5 patients. After surgical excision, chemotherapy was done with Taxol for each 2 patients of stage IV and V. After long term follow-up for mean 4 years, 4 patients died related with melanoma, 1 patient was recurred, and 11 patients were cured. Conclusion : The incidence of malignant melanoma was rare in Korea, but early involvement of lymph node at initial diagnosis was found in many cases (9/16, 56%). And then, early detection and appropriated excision as well as careful dissection of adjacent lymph nodes will offer the patient the best chance for cure.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6721-6726
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• 2013

Background: Changes in DNA methylation patterns are believed to be early events in hepatocarcinogenesis. A better understanding of methylation states and how they correlate with disease progression will aid in finding potential strategies for early detection of HCC. The aim of our study was to analyze the methylation frequency of tumor suppressor genes, P14, P15, and P73, and a mismatch repair gene (O6MGMT) in HCV related chronic liver disease and HCC to identify candidate epigenetic biomarkers for HCC prediction. Materials and Methods: 516 Egyptian patients with HCV-related liver disease were recruited from Kasr Alaini multidisciplinary HCC clinic from April 2010 to January 2012. Subjects were divided into 4 different clinically defined groups - HCC group (n=208), liver cirrhosis group (n=108), chronic hepatitis C group (n=100), and control group (n=100) - to analyze the methylation status of the target genes in patient plasma using EpiTect Methyl qPCR Array technology. Methylation was considered to be hypermethylated if >10% and/or intermediately methylated if >60%. Results: In our series, a significant difference in the hypermethylation status of all studied genes was noted within the different stages of chronic liver disease and ultimately HCC. Hypermethylation of the P14 gene was detected in 100/208 (48.1%), 52/108 (48.1%), 16/100 (16%) and 8/100 (8%) among HCC, liver cirrhosis, chronic hepatitis and control groups, respectively, with a statistically significant difference between the studied groups (p-value 0.008). We also detected P15 hypermethylation in 92/208 (44.2%), 36/108 (33.3%), 20/100 (20%) and 4/100 (4%), respectively (p-value 0.006). In addition, hypermethylation of P73 was detected in 136/208 (65.4%), 72/108 (66.7%), 32/100 (32%) and 4/100 (4%) (p-value <0.001). Also, we detected O6MGMT hypermethylation in 84/208 (40.4%), 60/108 (55.3%), 20/100 (20%) and 4/100 (4%), respectively (p value <0.001. Conclusions: The epigenetic changes observed in this study indicate that HCC tumors exhibit specific DNA methylation signatures with potential clinical applications in diagnosis and prognosis. In addition, methylation frequency could be used to monitor whether a patient with chronic hepatitis C is likely to progress to liver cirrhosis or even HCC. We can conclude that methylation processes are not just early events in hepatocarcinogenesis but accumulate with progression to cancer.

• Radiation Oncology Journal
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• v.12 no.3
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• pp.377-386
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• 1994

Purpose: The role of radiotherapy in the management of patients with locoregional recurrent cervix cancer after radical surgery were retrospectively analyzed. Methods and materials: Twenty-eight patients treated with radiotherapy for locoregional recurrence after primary surgery for carcinoma of the cervix between 1989 and 1993 were analyzed. The median follow-up of survivors was 15 months (ranged 7-43 months). Eight patients had their disease confined to the vagina and 19 patients($68\%$) had pelvic mass as part of their locoregional recurrent disease. Within 24 months after the initial surgery, $82\%$ of recurrences manifested themselves. All patients had whole pelvic irradiation with or without intracavitary radiotherapy(ICR). Results: Complete response(CR) was achieved in 18 patients($54\%$). Five of eighteen patients($28\%$) with initial CR developed second locoregional recurrence. Response to radiotherapy correlated strongly with tumor volume, site of recurrence and total radiation dose. The overall 2 year survival rate was $43\%$ and the disease free survival was $31\%$. Survival rate was significantly influenced by the factors of interval from operation to recurrence, size and site of recurrent tumor, radiation dose, response of radiotherapy, lymph node status as initial presentation, The principal cause of death was lung metastasis($36\%$). Conclusion: Radiotherapy is an excellent modality for control of locoregional recurrent cervix cancer. To improve local control and survival rate, whole pelvic external radiotherapy in addition to ICR with more than 75.0Gy at the depth of 1.0cm from vaginal mucosa is needed and frequent follow up and early detection of recurrence is suggested as well.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4669-4675
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• 2012

Objective: Nude mice with orthotopic transplantation of human ovarian epithelial cancer were used to investigate screening criteria for paraneoplastic normal ovarian tissue and the security of the freezing and thawing for ovarian tissue transplantation. Methods: Expression of CK-7, CA125, P53, survivin, MMP-2/TIMP-2 in paraneoplastic normal ovarian tissues were detected by RT-PCR as well as immunohistochemistry. The tissues of the groups with all negative indicators of RT-PCR, all negative indicators of immunohistochemistry, negative expression of CK-7, CA125 and survivin, positive expression of CK-7, CA125 and survivin, cancer tissues and normal ovarian tissues of nude mice were used for freezing and thawing transplantation, to analyze overt and occult carcinogenesis rates after transplantation. Results: When all indicators or the main indicators, CK-7, CA125 and survivin, were negative, tumorigenesis did not occur after transplantation. In addition the occult carcinogenesis rate was lower than in the group with positive expression of CK-7, CA125 and survivin (P<0.01). After subcutaneous and orthotopic transplantation of ovarian tissues, rates did not change (P>0.05). There was no statistical significance among rates after transplantation of ovarian tissues which were obtained under different severity conditions (P>0.05). Conclusion: Negative expression of CK-7, CA125 and survivin can be treated as screening criteria for security of ovarian tissues for transplantation. Immunohistochemical methods can be used as the primary detection approach. Both subcutaneous and orthotopic transplantation are safe. The initial severity does not affect the carcinogenesis rate after tissue transplantation. Freezing and thawing ovarian tissue transplantation in nude mice with human epithelial ovarian carcinoma is feasible and safe.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.6
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• pp.3937-3940
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• 2013

Objective: To explore the expression and significance of estrogen receptor (ER), progestrone receptor (PR), vascular endothelial growth factor (VEGF), CA15-3, CA125 and carcinoma embryonic antigen (CEA) expression in judging the prognosis of breast cancer. Materials and Methods: Sixty-five patients with breast cancer undergoing operations in the general surgery department were considered as the observation group, and 50 healthy outpatients of our hospital as the control group. Cubital venous blood was drawn in the morning from fasting patients in the two groups and chemiluminescence immunoassays were used to detect the levels of CA15-3, CA125 and CEA in serum. The follow-up duration was from 4 months to 2 years, and change in levels of the indicators was detected by dynamically drawing blood. After surgery, cancer tissue samples of patients in observation group remained on file (the non-recurrent patients were biopsied). Immunohistochemistry was applied to determine the expression of ER, PR and VEGF in tissue. Results: The effective rate of 12 patients with negative ER and PR expression was 33.3% in the observation group, being associated with prognosis to varying extents. Serum CA15-3, CA125 and CEA in the observation group were all significantly higher than in control group (p<0.01). With increase in pathological staging, levels of serum CA15-3, CA125 and CEA gradually increased (p<0.01). Levels in patients with lymph node metastasis were markedly higher than in those without (p<0.01). In addition, values with distal lymph node metastasis were notably higher than with adjacent lymph node metastasis (p<0.01). The postoperative follow-up results revealed that positive VEGF and levels of serum VEGF, CA15-3, CA125 and CEA in recurrence group were obviously higher than in non-recurrence group (p<0.01). Conclusions: Joint detection of ER and PR expression as well as levels of serum VEGF, CA15-3, CA125 and CEA is meaningful and can guide the diagnosis and treatment for breast cancer.

• Nuclear Medicine and Molecular Imaging
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• v.41 no.3
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• pp.185-193
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• 2007

This review focuses on the use of $^{18}F-FDG$ PET/CT to evaluate second primary cancers. The emergence of a second primary cancer is an important prognostic factor in cancer patients. The early detection of a second primary cancer and the appropriate treatment are essential for reducing the morbidity and mortality associated with these tumors. Integrated $^{18}F-FDG$ PET/CT, which can provide both the metabolic and anatomic information of a cancer, has been shown to have a better accuracy in oncology than either CT or conventional PET. The whole body coverage and high sensitivity of $^{18}F-FDG$ PET/CT along with its ability to provide both metabolic and anatomic information of a cancer make it suitable for evaluating a second primary cancer in oncology. Whole body $^{18}F-FDG$ PET/CT is useful for screening second primary cancers with a high sensitivity and good positive predictive value. In order to rule out the presence of a second primary cancer or an unexpected metastasis, further diagnostic work-up is essential when abnormal findings indicative of a second primary cancer are found on the PET/CT images. PET/CT is better in detecting a second primary tumor than conventional PET.