• Radiation Oncology Journal
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• v.26 no.1
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• pp.45-55
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• 2008

Purpose: This study evaluates the association of estrogen receptor(ER), progesterone receptor(PR), Her-2, COX-2, and survivin with the clinicopathological features and outcomes in young Korean women with breast cancer using recently developed tissue microarray(TMA) technology. Materials and Methods: A cohort of 212 young patients with breast cancer diagnosed at the age of 45 years or younger from March 1994 to August 2005, were enrolled in this study. The age range of patients was $23{\sim}45$ years(median age, 39 years). The minimum and median follow-up periods were 24 months and 60 months, respectively. Serial sections of primary tumors were processed by the use of a TMA for immunohistochemical staining for five biomarkers. The correlation of these five biomarkers and the clinicopathological features and outcomes were analyzed by statistical methods. Results: The majority of the patients were stage T1(90 patients) or T2(101 patients), and 105 patients(49.5%) had an axillary node metastasis. The 5-year overall and relapse free survival rates for all of the patients were 90.4% and 82.3%, respectively, and 36 patients had a locoregional or distant metastasis as a first event. Positive expression of ER, PR, Her-2, COX-2, and survivin was determined in 38.2%, 45.3%, 25.9%, 41.5%, and 43.4%, of the tumor samples, respectively. Tumor stage, nodal status, age, as well as expression of ER, PR, and HER-2 status were significantly associated with the disease free survival rate. Tumor stage, nodal status, as well as expression of ER, PR, and HER-2 were significantly related with the overall survival rate. Expression of COX-2 and survivin were not single independent prognostic factors for the disease free and overall survival rate although co-expression of HER-2 and COX-2 had a tendency as a poor prognostic factor. By multivariate analysis, only T stage and lymph node status were significant prognostic factors, and ER status was a marginally significant prognostic factor(p=0.075). Conclusion: Expression of ER, PR and HER-2 were significant prognostic factors for the relapse free and overall survival rate. Expression of COX-2 and survivin were not prognostic factors for young women with breast cancer.

• Journal of Chest Surgery
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• v.39 no.11 s.268
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• pp.805-809
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• 2006

Background: In our previous study, we demonstrated that transforming growth factor-beta 1 receptor II(TGF-${\beta}1RII$) may have a role in the formation of bullae. In this study, we investigated if expression of transforming growth factor-beta 1 (TGF-${\beta}1$) ligand was altered in a bullous lung tissue by immunohistochemical staining of bullous tissues from patients with primary spontaneous pneumothorax. Material and Method: Bullous lung tissues were obtained from 36 patients with primary spontaneous pneumothorax, including 34 males and 2 females aged 14 to 38 years old. Result: Of the 36 patients, 19 were TGF-${\beta}1$ positive and 24 were transforming growth factor-beta 1 receptor II(TGF-${\beta}1RII$) positive. Among the 19 TGF-${\beta}1$ positives, 15 were also TGF-${\beta}1RII$ positive, observation at high magnification showed that strong immunohistochemical stain was detected in the boundary region between the bullous and normal lung tissues. Conclusion: These results suggest that overexpression of TGF-${\beta}1$ may be involved in the formation of a bulla as well as the alteration of TGF-${\beta}1RII$ expression. Further molecular studies are needed to elucidate the more detailed molecular mechanisms of the bulla formation.

• Journal of Food Hygiene and Safety
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• v.6 no.1
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• pp.1-12
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• 1991

Fischer 344 rats aged six weeks were diYided into four groups and group 1, 2, and 3 of rats were given an intraperitoneal injection of diethylnitrosamine at 200 mg/kg body weight and group 4 was given saline alone. Two weeks after beginning of the experiment, group 1 and 2 of rats were begun to feed on diets containing 0.02% 2-acetylaminofluorene as a promoter for four weeks. Three weeks after beginning of the experiment, all groups were performed partial hepatectomy. During the last two weeks, group 1 and 3 of rats were received subcutaneously 3 consecutive weekly doses of iron dextran at 0.125 ml/100 g body weight. Subcutaneous injection of iron dextran resulted in hepatic siderosis in group 1 and 3 of rats. Pre neoplastic nodules were identified histopathologically by two markers, resistance to exogenous iron accumulation and glutathione S-transeferase placental form (GST-P) activity, while early carcinogen induced foci were hardly resistant to iron accumulation and though a few lesions were identified, it could hardly be distincted from normal hepatocytes of surroundings. However, GST-P positive nodules as well as foci were clearly distincted from normal hepatic cells of surroundings. In the quantitative analysis of carcinogen-induced nodules and foci, more lesions were detected by immunohistochemical method for GST-P than by prussian blue staining for resistant to iron accumulation. It is concluded that immunohistochemical marker for GST-P is more sensitive and reliable than iron-resistance marker, and that iron-resistance is not useful marker for early detection of carcinogen-induced hepatic lesions.

• Tuberculosis and Respiratory Diseases
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• v.54 no.1
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• pp.80-90
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• 2003

Background : Goblet cell hyperplasia is a critical pathological feature in hypersecretory diseases of the airways. A bacterial infection of the lung is also known to induce inflammatory responses, which can lead to the overproduction of mucus. Recently, mucin synthesis in the airways has been reported to be regulated by neutrophilic inflammation-induced epidermal growth factor receptor (EGFR) expression and activation. In addition, it was reported that migration of the activated neutrophils is dependent on the matrix metalloproteinases (MMPs), especially MMP-9. In this study, bacterial lipopolysaccharide (LPS)-induced goblet cell hyperplasia and mucus hypersecretion by EGFR cascade, resulting from the MMPs-dependent neutrophilic inflammation were investigated in the rat airways. Methods : Pathogen-free Sprague-Dawley rats were studied in vivo. Various concentrations of LPS were instilled into the trachea in $300{\mu}{\ell}$ PBS (LPS group). Sterile PBS ($300{\mu}{\ell}$) was instilled into the trachea of the control animals (control group). The airways were examined on different days after instilling LPS. For an examination of the relationship between the LPS-induced goblet cell hyperplasia and MMPs, the animals were pretreated 3 days prior to the LPS instillation and daily thereafter with the matrix metalloproteinase inhibitor (MMPI; 20 mg/Kg/day of CMT-3; Collagenex Pharmaceuticals, USA). The neutrophilic infiltration was quantified as a number in five high power fields (HPF). The alcian blue/periodic acid-Schiff (AB/PAS) stain were performed for the mucus glycoconjugates and the immunohistochemical stains were performed for MUC5AC, EGFR and MMP-9. Their expressions were quantified by an image analysis program and were expressed by the percentage of the total bronchial epithelial area. Results : The instillation of LPS induced AB/PAS and MUC5AC staining in the airway epithelium in a time- and dose-dependent manner. Treatment with the MMPI prevented the LPS-induced goblet cell hyperplasia significantly. The instillation of LPS into the trachea induced also EGFR expression in the airway epithelium. The control airway epithelium contained few leukocytes, but the intratracheal instillation of LPS resulted in a neutrophilic recruitment. A pretreatment with MMPI prevented neutrophilic recruitment, EGFR expression, and goblet cell hyperplasia in the LPS-instilled airway epithelium. Conclusion : Matrix metalloproteinase is involved in LPS-induced mucus hypersecretion, resulting from a neutrophilic inflammation and EGFR cascade. These results suggest a potential therapeutic role of MMPI in the treatment of mucus hypersecretion that were associated with a bacterial infection of the airways.

• Journal of Life Science
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• v.27 no.4
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• pp.383-389
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• 2017

This study intends to analyze the contents of rutin, procyanidin B3, quercetin, kaempferol, known to have antioxidant, anti-inflammatory and anti-carcinogenic effects, among the polyphenol type contained in the grape pruning stem extracts (GPSE), utilizing grape stems being discarded after harvest, measure the effects on the skin moisture, inhibition of skin cell proliferation, anti-inflammatory on the damaged skin of a HR-1 mice induced with UVB, and verify the applicability as a material for functional food and functional cosmetics. The results of verifying the photoprotection effects through the skin proliferation control through of GPSE showed similar result to suncream was achieved at the GPSE concentration of 2,000 mg/kg on the epidermis (p<0.05). The results showed anti-inflammatory effects on all groups applied with GPSE as compared to the control group irradiated with UVB, but at the GPSE concentration of 1,000 mg/kg, a lower COX-2 protein expression at 8%, lower than the 22% of suncream, was observed to achieve an excellent anti-inflammatory effect (p<0.05). The results of this study confirmed the existence of active polyphenol type, such as rutin, kaempferol, querocetin and procyanidin B3, within the GPSE, and GPSE has improvement effects on moisturizing effects, skin proliferation control effect, inflammatory control effect and improvement effects on the skin barrier function through UV ray damage. GPSE is a functional ingredient with a potential for skin protection effects, and has high utilization as an ingredient for functional food and functional cosmetics.

• Tuberculosis and Respiratory Diseases
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• v.39 no.6
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• pp.502-510
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• 1992

Background: Neuron specific enolase (NSE) is a neuronal form of the glycolytic enzyme enolase which was first found in extracts of brain tissue, and later in a variety of APUD cells and neurons of the diffuse endocrine system. SCLC shares many APUD properties with normal neuroendocrine cells. NSE immunostaining and serum NSE measurement may be a useful marker of neuroendocrine differentiation in lung tumors and diagnosis of small cell carcinoma. Methods: NSE immunohistochemical staining was done and at the same time serum NSE levels were measured in 22 small cell lung cancer and 21 non small cell lung cancer which were confirmed histologically. Results: 1) NSE immunoreactivity was detected in 9 of the 18 (50%) small cell lung cancer, in 5 of the 16 non small cell lung cancer. 2) Whereas the mean value in non-small cell lung cancer group was $11.79{\pm}4.47\;ng/ml$, the mean level of serum NSE in small cell lung cancer increased up to $59.3{\pm}77.8\;ng/ml$. In small cell lung cancer patients, mean value of limited disease group was $20.19{\pm}12.91\;ng/ml$, while mean value of extended disease group was $91.9{\pm}94.2\;ng/ml$ showing statistically significant difference. If serum levels above 20 ng/ml were tentatively defined as positive, 16 of 22 (73%) patients with SCLC had positive serum NSE level, but only one patient with NSCLC did. There was no correlation between serum NSE level and immunoreactivity of NSE. Conclusion: These studies indicate that serum NSE measurement may be a useful marker for the diagnosis and disease extent and NSE immunostaining can be used to demonstrate the neuroendocrine components of lung tumor.

• Journal of Gastric Cancer
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• v.8 no.4
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• pp.182-188
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• 2008

Purpose: Transcriptional factors of CREB (cAMP response element binding protein) are involved in regulating the gene expression in response to a variety of signaling pathways. The proteins produced by the CREB genes play key roles in many physiological processes, including memory and long-term potentiation. The retinoic acid receptor (RAR) axis mediates epithelial cell differentiation and proliferation in many tissues. This study examined the expressions of RAR and CREB and their relationship with the clinicopathologic factors and their significance. Materials and Methods: The levels of the RAR and CREB expressions were measured in 150 gastric adenocarcinomas by performing immunohistochemical staining. Results: 1. An RAR protein expression was found in 63.3% of the adenocarcinomas (95/150) and a CREB expression was found in 60.7% (91/150) of the adenocarcinomas. 2. An RAR protein expression was found in 72.2% (78/108) of the intestinal type adenocarcinomas and in 40.5% (17/42) of the diffuse type adenocarcinomas (P<0.05). Based on the depth of invasion, an RAR protein expression was found in 58.3% (14/24) of the T1 adenocarcinomas, in 61.9% (13/21) of the T2 adenocarcinomas, in 63.5% (61/96) of the T3 adenocarcinomas, in 77.8% (7/9) of the T4 adenocarcinomas and in 74.7% (62/83) of the adenocarcinomas with lymph node metastasis and in 49.2% (33/67) of the adenocarcinomas without lymph node metastasis (P<0.01). 3. A CREB expression was found in 69.4% (75/108) of the intestinal type and in 38.1% (16/42) of the diffuse type (P>0.05). Based on the depth of invasion, a CREB expression was found in 50% (12/24) of the T1 adenocarcinomas, in 52.4% (11/21) of the T2 adenocarcinomas, in 64.6% (62/96) of the T3 adenocarcinomas, in 66.6% (6/9) of the T4 adenocarcinomas, in 71.1% (59/83) of the adenocarcinomas with lymph node metastasis and in 47.8% (32/67) of the adenocarcinomas without lymph node metastasis (P<0.01). 4. The RAR protein and CREB expressions coincided in 71.4% of the gastric adenocarcinomas and a significant correlation between them was found (P<0.05). Conclusion: We found a significant relationship between the expression of RAR and CREB and the histology and lymph node metastasis of gastric cancer. Further studies are needed to confirm their biologic meaning in gastric carcinogenesis.

• Tuberculosis and Respiratory Diseases
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• v.57 no.4
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• pp.345-350
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• 2004

Background : To evaluate the frequency and clinical significance of lymph node micrometastasis in patients of non-small-cell lung cancer pathologically staged to be T1-2,N0. Method : From consecutive 29 patients of non-small-cell lung cancer who received curative operation and routine systemic nodal dissection, we immunohistochemically examined 806 lymph nodes from mediastinal, hilar and peribronchial lesion. All slides were stained with hematoxylin and eosin staining for one section and with cytokeratin AE1/AE3 antibody for another consecutive section of same lymph node to find out micrometastasis. Results : In 806 lymph nodes examined, no tumor cell was seen on hematoxylin and eosin staining and micrometastic foci were shown to be on 0.37%(3) of 806 lymph nodes, in which were upper paratracheal, interlobar and peribronchial lymph node. These three positive stains constitute 10.3%(3) of the 29 patients with non-small-cell lung cancer. Nine patients died from disease progression(4), postoperative complication(3) and concomitant diseases(2). The four patients with disease progression did not show evidence of micrometastasis on their lymph node examination. Conclusion : The frequency of lymph node micrometastasis was in 0.37% of 806 lymph nodes examined. The study results might suggested that routine analysis of micrometastasis on the lymph node didn't give any clinical implication on patients with non-small-cell lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.44 no.4
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• pp.756-765
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• 1997

Background : To study the prognosis of patients with lung cancer, many investigators have reported the methods to detect cell proliferation in tissues including PCNA, thymidine autoradiography, flow cytometry and Ki-67. PCNA, also known as cyclin, is a cell related nuclear protein with 36KD intranuclear polypeptide that is maximally elevated in S phase of proliferating cells. In this study, PCNA was identified by paraffin-embedding tissue using immunohistochemistry which has an advantage of simplicity and maintenance of tissue architecture. The variation of PCNA expression is known to be related with proliferating fraction, histologic type, anatomic(TNM) stage, degree of cell differentiation, S-phase fraction and survival rate. We analyzed the correlation between PCNA expression and S-phase fraction, survival. Method : To investigate expression of PCNA in primary lung cancer, we used immunohistochemical stain to paraffin-embedded sections of 57 resected primary non-small cell lung cancer specimen and the results were analyzed according to the cell type, cell differentiation, TNM stage, S-phase fraction and survival. Results : PCNA expression was divided into five group according to degree of staging(-, +, ++, +++, ++++). Squamous cell type showed high positivity than in adenocarcinoma. Nonsignificant difference related to TNM stage was noticed. Nonsignificant difference related to degree of cell differentiation was noticed. S-phase fraction was increased with advance of PCNA positivity, but it could not reach the statistic significance. The 2 year survival rate and median survival time were -50% 13 months, +75% 41.3 months, ++73% 33.6 months, +++67% 29.0 months, ++++25% 9 months with statistic significance (P<0.05, Kaplan-Meier, generalized Wilcox). Conclusion : From this study, PCNA expression was high positive in squamous cell cancer. And, there was no relationship between PCNA positivity and TNM stage, cellular differentiation or S-phase fraction. But, the patients with high positive PCNA staining showed poor survival rate than the patients with lower positive PCNA staining (p<0.05). It was concluded that PCNA immunostaining is a simple and useful method for survival prediction in paraffin embedded tissue of non-small cell lung cancer.

• Applied Microscopy
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• v.32 no.4
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• pp.385-398
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• 2002

The purpose of the present study is to investigate whether stromal cells supporting specific microenvironment for hematopoiesis of bone marrow are affected by toxicants and therapeutic drugs such as antibiotics and anticancer drugs and whether laminin-1 is associated with such effects. SD rats were intraperitoneally injected with 75 mg/kg of cyclophosphamide which is widely used to treat infant's solid tumor, leukemia and myeloma and sacrificed after 3 days, 1 week, 3 weeks or 5 weeks of injection. The bone marrow extracted and paraffin-sectioned was analyzed using immunohistochemical staining. A part of tissues was subjected to electron microscopy following reaction with rabbit anti-laminin antibody, biotinylated goat anti-rabbit IgG conjugated with 12 nm gold particles, and staining with uranyl acetate. 1. The bone marrow tissue at day 3 post injection with cyclophosphamide displayed dilated venous sinus, partial necrotic death, and decreased number of hematopoietic cells. Laminin-1 was intensively stained in the reticular and adipose tissues. 2. Up to 5 weeks post injection, laminin-1 was stained at a low level in the stromal tissue of bone marrow and the number of hematopoietic cell was increased. 3. Deposition of the gold particle which represents laminin-1 expression was observed at the highest level in the stromal cells of bone marrow obtained 3 days after injection, and decreased after 1 to 5 weeks. These results suggest that stromal cells which play a role in supporting microenvironment for bone marrow hematopoiesis augment induction of laminin-1 expression and activation upon administration of cyclophosphamide.