• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.3319-3322
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• 2013

Background: Helicobacter pylori (H. pylori) is one of the risk factors for gastric cancer (GC). Any prognostic effect of HER-2 status in gastric lymph node metastasis in H. pylori positive cases is unknown. Materials and Methods: A total of 74 patients, 47 (64%) male, and 27 (34%) female, who had subtotal or total gastrectomy and also positive lymph nodes, were included in the study. Age range was 29-87 years, and median age was 58 years. HER-2 expression was assessed in both gastric resection samples and lymph node material with carcinoma metastasis of the same patient by immunohistochemistry (IHC) and silver in situ hybridization (SISH) methods. H. pylori status was examined in gastric materials of all patients. Relationships between HER-2 status in gastric cancers and lymph nodes and H. pylori status were investigated. Results: H. pylori was positive in 40 cases (54%), and negative in 34 (46%). While in the primary tissues of H. pylori positive cases, SISH positivity for HER-2 was observed in 13 cases (86%), SISH negativity was observed in 2 (14%), in metastatic lymph nodes 21 cases (72%) were SISH positive and 8 cases (28%) were SISH negative (P=0.005 and P=0.019, respectively). Initial CEA values were high in 18 cases (78%) with positive H. pylori and in 5 cases (22%) with negative H. pylori (P=0.009). While SISH data of patients were negative in 59 cases (80%) and positive in 15 cases (20%) in primary tissues, they were negative in 56 cases (75%) and positive in 18 cases (25%) in lymph nodes. Discrepancy between primary tissue and lymph node results was detected in 3 cases, in which SISH was negative in the primary tissue and HER-2 expression was positive in the lymph nodes. Conclusions: Clinical progression was poor in H. pylori positive cases with HER-2 negativity in primary gastric tissue, but HER-2 positivity in the lymph nodes. SISH positivity can be expected in H. pylori positive cases, and it may be predicted that these cases can benefit from trastuzumab treatment.

• The Korean Journal of Nuclear Medicine
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• v.31 no.1
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• pp.108-115
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• 1997

$^{131}I-6{\beta}$-iodomethyl-19-norcholesterol(NP-59) has an advantage to assess adrenal dysfunction caused by adrenal cortical disorders. The aim of this study is to evaluate the clinical usefulness of NP-59 scintigraphy in each adrenal disease. Ten patients who did eleven NP-59 adrenal scintigraphies at Dong-A University Hospital from March 1990 to December 1996 were selected as the subject. Among the subject there were 5 cases of Cushing's syndrome, 2 cases of incidentaloma, 1 case of metastatic adrenal tumor, liver cirrhosis with hirsutism and hypertension respectively. Among 5 cases of Cushing's syndrome, there were 2 cases of Cushing's disease, 2 cases of adrenal adenoma and 1 case of adrenal carcinoma. There are no disagreement between clinical diagnosis and scan finding in Cushing's syndrome. In 2 incidentaloma cases, even though one is interpretated as a functioning tumor, both of 2 cases could avoid unnecessary biopsy according to scintigraphy result. One case of hirsutism, clinically adrenal originated, revealed the normal scintigraphic finding after dexamethasone suppression scan. It could suggest that the etiology of hirsutism was extra-adrenal origin. One case of hypertension took the study to exclude the possibility of primary aldosteronism. Normal suppression scan finding revealed that primary aldosteronism did not exist in this case. In conclusion, NP-59 scintigraphy was very useful in diagnosis and differential diagnosis of Cushing's syndrome and it could avoid unnecessary biopsy in the incidental adrenal tumor.

• The Journal of the Korean Society for Microbiology
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• v.14 no.1
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• pp.89-97
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• 1979

Nonspecific suppressions of the immune responses have been reported to occur in the cancer-bearing patients. The mechanisms responsible for these immunosuppressions remain unclear but some investigators suggested that the immunosuppressions may result from immunosuppressive factors exudated from tumor masses. This study was undertaken to evaluate the in vivo effects of ascitic and pleural fluids from patients with cancers metastatic to peritoneum or pleura on the immune responses of mice. Non-cancerous ascitic and pleural effusions were used as controls. The ascitic fluids from hepatomap atients and pleural fluids from pulmonary carcinoma patients decreased both the delayed-type hypersensitivity and the antibody formation only when these were injected before antigenic stimulation. Control effusions exerted no effect on the immune responses to mice. These results suggested that cancerous fluids suppressed the immune responses by affecting the afferent arc of the immune system.

• Korean Journal of Head & Neck Oncology
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• v.14 no.2
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• pp.228-235
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• 1998

Objectives: Papillary microcarcinoma of the thyroid was evaluated as to the effectiveness of diagnostic modalities, lymphatic spread pattern, and therapeutic decision according to tumor size. Material and Methods: We retrospectively analyzed a clinicopathologic findings of 72 papillary microcarcinoma patients who were treated at the over 11 years between 1985 and 1995. The authors divided papillary microcarcinoma of the thyroid into two subgroups according to tumor size: $0{\leqq}5mm$ and $5<0{\leqq}10mm$. An analysis including age and gender distribution, diagnostic tools(thyroid sonogram, thyroid scan, thyroid function test, fine needle aspiration cytology, frozen section), pathological examination of lymphnode, and surgical procedures was carried out in each subgroups. Results: The carcinoma of smaller than 5mm were found in 32 patients, and of 6 -10mm were in 40 patients. The average age of patients was 45years and all of them were female. Cold nodules on thyroid scan were noticed in 53 patientss and normal findings were in 15 patients. Suspicious malignant lesions(fine calcification, solid mass, irregular margin) on thyroid sonography were detected in 23 patients and the sonography was more useful in detecting $0{\leqq}5mm$ small sized lesions than other diagnostic methods. FNAC were performed in 17 patients, and 7 patients were diagnosed as having thyroid papillary cancer. But diagnotic rate in $0{\leqq}5mm$ small sized lesions was very low(one of eights).Frozen section were performed in all patients, among these 15 patients were diagnosed as being benign diseases and false negative rates were higher in $0{\leqq}5mm$ small sized lesions than in $5<0{\leqq}10mm$ sized lesions(p-value<0.006). Only thyroidectomies were performed in 24 patients and thyroidectomy with node dissections in 48 patients. The lymphnode metastatic rates were much higher in multifocal lesions(61.5%) than in single lesion. The incidence of cervical lymphnode metastasis was 19.4% in $0{\leqq}5mm$ sized lesions and 47.9% in $5<0{\leqq}10mm$ sized lesions. Postoperative management were performed with TSH suppression therapy(T4, synthroid) in all patients and RI therapy in 29 patients. Conclusion: On the basis of our study, improved preoperative diagnostic tools for papillary microcarcinoma of the thyroid was helpful in the choice of surgical treatment. As a result of techninological progress(ultrasonography, FNAC), the pencentage of the discovery of papillary microcarcinoma has been increased. The thyroid ultrasonography was useful in detecting small sized lesions($0{\leqq}5mm$), but FNAC may not be beneficial in detecting small sized lesions($0{\leqq}5mm$). In the surgical procedure, thyroid lobectomy alone should be avoided because of the high rate of bilaterality and multifocality.

• Korean Journal of Head & Neck Oncology
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• v.30 no.2
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• pp.53-61
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• 2014

Background and Objectives : Anaplastic thyroid carcinoma(ATC) is a rare but highly aggressive thyroid malignancy that is associated with an extremely poor survival despite the best multidisciplinary care. BRAF(V600E) mutation is detected in about a quarter of ATC, but unlike its high treatment response to selective BRAF inhibitor (PLX4032) in metastatic melanoma, the treatment response of ATC is reported to be low. The purpose of this study is to investigate the innate resistance mechanism responsible for this low treatment response to BRAF inhibitor and its effect on epithelial-mesenchymal transition(EMT). Materials and Methods : Two ATP cell lines, 8505C and FRO were selected and treated with PLX4032 and its drug sensitivity and effects on cell migration and EMT were examined and compared. Further investigation on the changes in signals responsible for the different treatment response to PLX4032 was carried out and the same experiment was performed on both orthotopic and ectopic xenograft mouse models. Results : FRO cell line was more sensitive to PLX4032 treatment compared to 8505C cell line. The resistance to BRAF inhibition in 8505C was due to increased expression of EGFR. Effective inhibition of both EGFR and p-AKT was achieved after dual treatment with BRAF inhibitor(PLX4032) and EGFR inhibitor(Erlotinib). Similar results were confirmed on in vivo study. Conclusion : EGFR-mediated reactivation of the PI3K/AKT pathway and MAPK pathway contributes to the relative insensitivity of BRAF(V600E) mutant ATC cells to PLX4032. Dual inhibition of BRAF and EGFR leads to sustained treatment response including cell invasiveness.

• Tuberculosis and Respiratory Diseases
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• v.43 no.6
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• pp.1008-1018
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• 1996

Primary mediastinal nonseminomatous germ cell tumor is extremely rare. Apart from rarity and large size, mediastinal germ cell tumors show striking similarity to testicular tumors in age, incidence, and tumor type. The symptoms associated with these tumors are related mainly to size, invasion of neighboring structures, and distant metastases. Tissue diagnosis is obtained by biopsy of the primary lesion or by biopsy of metastatic sites. Tumors often present with advanced bulky disease, which are unresectable. So these tumors require an aggressive multidisciplinary approach to management. Optimal management includes aggressive surgical debulking and early use of cisplatin-bleomycin-based combination chemotherapy. Serial biomarker measurements permit early recognition of recwrence and improved timing of surgical intervention. The prognosis for mediastinal germ cell tumors is poor, not only because they are far advanced at the time of diagnosis but also because some of the tumors-such as embryonal carcinomas, choriocarcinomas, and endodermal sinus tumors-are very aggressive. In these cases, we present three young male patients with large mass on anterior mediastinum. Tissue diagnosis was obtained by primary lesion biopsy. All patients received surgical debulking and combination chemotherapy and experienced a brief response and eventually had relapses. We report these cases with a review of literatures.

• Biomolecules & Therapeutics
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• v.30 no.4
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• pp.340-347
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• 2022

Advanced or metastatic breast cancer affects multiple organs and is a leading cause of cancer-related death. Cancer metastasis is associated with epithelial-mesenchymal metastasis (EMT). However, the specific signals that induce and regulate EMT in carcinoma cells remain unclear. PRR16/Largen is a cell size regulator that is independent of mTOR and Hippo signalling pathways. However, little is known about the role PRR16 plays in the EMT process. We found that the expression of PRR16 was increased in mesenchymal breast cancer cell lines. PRR16 overexpression induced EMT in MCF7 breast cancer cells and enhances migration and invasion. To determine how PRR16 induces EMT, the binding proteins for PRR16 were screened, revealing that PRR16 binds to Abl interactor 2 (ABI2). We then investigated whether ABI2 is involved in EMT. Gene silencing of ABI2 induces EMT, leading to enhanced migration and invasion. ABI2 is a gene that codes for a protein that interacts with ABL proto-oncogene 1 (ABL1) kinase. Therefore, we investigated whether the change in ABI2 expression affected the activation of ABL1 kinase. The knockdown of ABI2 and PRR16 overexpression increased the phosphorylation of Y412 in ABL1 kinase. Our results suggest that PRR16 may be involved in EMT by binding to ABI2 and interfering with its inhibition of ABL1 kinase. This indicates that ABL1 kinase inhibitors may be potential therapeutic agents for the treatment of PRR16-related breast cancer.

• Korean Journal of Radiology
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• v.24 no.5
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• pp.384-394
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• 2023

Objective: Mammographic density is an independent risk factor for breast cancer that can change after neoadjuvant chemotherapy (NCT). This study aimed to evaluate percent changes in volumetric breast density (ΔVbd%) before and after NCT measured automatically and determine its value as a predictive marker of pathological response to NCT. Materials and Methods: A total of 357 patients with breast cancer treated between January 2014 and December 2016 were included. An automated volumetric breast density (Vbd) measurement method was used to calculate Vbd on mammography before and after NCT. Patients were divided into three groups according to ΔVbd%, calculated as follows: Vbd (post-NCT - pre-NCT)/pre-NCT Vbd × 100 (%). The stable, decreased, and increased groups were defined as -20% ≤ ΔVbd% ≤ 20%, ΔVbd% < -20%, and ΔVbd% > 20%, respectively. Pathological complete response (pCR) was considered to be achieved after NCT if there was no evidence of invasive carcinoma in the breast or metastatic tumors in the axillary and regional lymph nodes on surgical pathology. The association between ΔVbd% grouping and pCR was analyzed using univariable and multivariable logistic regression analyses. Results: The interval between the pre-NCT and post-NCT mammograms ranged from 79 to 250 days (median, 170 days). In the multivariable analysis, ΔVbd% grouping (odds ratio for pCR of 0.420 [95% confidence interval, 0.195-0.905; P = 0.027] for the decreased group compared with the stable group), N stage at diagnosis, histologic grade, and breast cancer subtype were significantly associated with pCR. This tendency was more evident in the luminal B-like and triple-negative subtypes. Conclusion: ΔVbd% was associated with pCR in breast cancer after NCT, with the decreased group showing a lower rate of pCR than the stable group. Automated measurement of ΔVbd% may help predict the NCT response and prognosis in breast cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.15
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• pp.6047-6052
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• 2014

Background: Weight loss during chemotherapy has not been exclusively investigated. Macrophage inhibitory cytokine-1 (MIC-1) might play a role in its etiology. Here, we investigated the prognostic value of weight loss before chemotherapy and its relationship with MIC-1 concentration and its occurrence during chemotherapy in patients with advanced esophageal squamous cell carcinoma (ESCC). Materials and Methods: We analyzed 157 inoperable locally advanced or metastatic ESCC patients receiving first-line chemotherapy. Serum MIC-1 concentrations were assessed before chemotherapy. Patients were assigned into two groups according to their weight loss before or during chemotherapy:>5% weight loss group and ${\leq}5%$ weight loss group. Results: Patients with weight loss>5% before chemotherapy had shorter progression-free survival period (5.8 months vs. 8.7 months; p=0.027) and overall survival (10.8 months vs. 20.0 months; p=0.010). Patients with weight loss >5% during chemotherapy tended to have shorter progression-free survival (6.0 months vs. 8.1 months; p=0.062) and overall survival (8.6 months vs. 18.0 months; p=0.022), and if weight loss was reversed during chemotherapy, survival rates improved. Furthermore, serum MIC-1 concentration was closely related to weight loss before chemotherapy (p=0.001) Conclusions: Weight loss both before and during chemotherapy predicted poor outcome in advanced ESCC patients, and MIC-1 might be involved in the development of weight loss in such patients.

• Tuberculosis and Respiratory Diseases
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• v.50 no.2
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• pp.171-181
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• 2001

Background : Angiogenesis is an essential process for the growth and metastatic ability of solid tumors. One of the key factors known to be capable of stimulating tumor angiogenesis is the vascular endothelial growth factor (VEGF). The serum VEGF concentration has been shown to be a useful parameter related to the clinical features and prognosis of lung cancer and has been recently applied to a the malignant pleural effusion showing a correlation with the biochemical parameters. The VEGF has been shown to play a role in the inflammatory diseases, but rarely in the tuberculosis (TB). The serum and pleural fluid VEGF levels were measured in patients with lung cancer and TB. Their relationship with the clinical and laboratory parameters and repeated measurement 3 months after various anticancer treatments were evaluated to assess the utility of the VEGF as a tumor marker. Methods : Using a sandwich enzyme-linked immunosorbent assay, the VEGF conoentration was measured in both sera and pleural effusions collected from a total of 85 patients with lung cancer, 13 patients with TB and 20 healthy individuals. Results : The serum VEGF levels in patients with lung cancer ($619.9{\pm}722.8pg/ml$) were significantly higher than those of healthy controls ($215.9{\pm}191.1pg/ml$), However, there was no significant difference between the VEGF levels in the lung cancer and TB patients. The serum VEGF levels were higher in large cell and undifferentiated carcinoma than in squamous cell carcinoma and adenocarcinoma. The serum VEGF levels of lung cancer patients revealed no significant relationship with the various clinical parameters. The VEGF concentrations in the malignant effusion ($2,228.1{\pm}2,103.0pg/ml$) were significantly higher than those in the TB effusion ($897.6{\pm}978.8pg/ml$). In the malignant pleural effusion, the VEGF levels revealed significant correlation with the number of red blood cells (r=0.75), the lactate dehydrogenase (LDH)(r=0.70), and glucose concentration (r=-0.55) in the pleural fluid. Conclusion : The serum VEGF levels were higher in the lung cancer patients. The VEGF levels were more elevated in the malignant pleural effusion than in the tuberculous effusion. In addition, the VEGF levels in the pleural fluid were several times higher than the matched serum values suggesting a local activation and possible etiologic role of VEGF in the formation of malignant effusions. The pleural VEGF levels showed a significant correlation with the numbers of red blood cells, LDH and glucose concentrations in the pleural fluid, which may represent the tumor burden.