• Journal of Chest Surgery
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• v.41 no.4
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• pp.447-456
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• 2008

Background: Caspase-3 is a cysteine protease that plays a major role in the process of apoptotic cell death. The dysregulated expression of c-myc contributes to the tumorigenesis in a variety of human cancers. The aim of this study was to investigate the expressions of caspase-3 and c-myc and their significances as prognosis markers in patients with completely resected non-small cell lung cancer (NSCLC). Material and Method: A total 130 consecutive patients who had undergone complete resection without pre-operative radio-therapy or chemotherapy between May 1996 and December 2003 for NSCLC were retrospectively reviewed. The median follow-up period of the patients was 50 months (range: $3{\sim}128$ months). The expressions of caspase-3 and c-myc were immuno-histochemically examined, and these were correlated with the clinico-pathologic data. Result: The prevalence of caspase-3 and c-myc expressions in the patients was 68% (88/130) and 59% (77/130), respectively. Significant association was found between the frequency of the expressions of caspase-3 and c-myc (p=0.025). The caspase-3 and c-myc expressions were not significantly associated with the prognosis in all the patients. However, according to stages, a positive caspase-3 expression was significantly correlated with a favorable prognosis for patients with stage IIIa disease (median survival period: 35 months vs. 10 months, p=0.021). Multivariate analysis showed the pathologic stage to be significantly correlated with a good prognosis in all the patients (p=0.024), and with a positive caspase-3 expression, well differentiated tumor and negative neuronal invasion in the patients with stage llla disease (p=0.005, p=0.003, p=0.004, respectively). Conclusion: Caspase-3 and c-myc were frequently expressed in NSCLC, suggesting its possible involvement in tumor development. The caspase-3 expression, as determined with performing immunohistochemical staining, may be a favorable prognostic indicator in patients with completely resected NSCLC an advanced stage (IIIa).

• Radiation Oncology Journal
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• v.17 no.3
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• pp.203-208
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• 1999

Purpose : To evaluate whether spontaneous apoptosis has prognostic value among patients with squamous cell carcinoma of lung. Materials and Methods : Material from 19 patients who received thoracic irradiation between 1990 and 1994 was analyzed. Their stages were II (1), IIIa (8), IIIb (5), and IV (5). Patients were observed from 5 to 67 months (median : 17 months). The spontaneous apoptosis index (AI) and p53 mutation were measured by immunohistochemical stains. Results : AI was found to range from 0 to $1\%$ (median $0.4\%$). Patients with low AI ($AI{\leq}$median) had a much higher distant metastasis rate at diagnosis than patients with high AI. By analysis of prognostic factors for survival, M stage was significant in univariate analysis. AI, chemotherapy, M stage, T stage, and stage were significant in multivariate analysis. The correlation between the AI and p53 mutation was not seen. Conclusion : AI was related with distant metastasis at diagnosis and not with p53 mutation. Also low AI group tended to have shorter survival time than high AI group.

• Journal of Radiation Protection and Research
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• v.37 no.4
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• pp.208-212
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• 2012

In previous studies, ovarian follicle in rat has been used a higher radiation dose than that for cancer radiotherapy in clinical practice. The aim of this study was to evaluate the effect of radiation dose used for cancer radiotherapy on ovarian follicle atresia in rat. Mice of 4-week-old female were whole body irradiated with 2 cGy or 2 Gy (Mevatron 67, Siemens, Germany) and sacrificed by cervical dislocation. Ovaries were collected at 24 hours after irradiation to observe the degree of follicular atresia. Ovaries were fixed in neutral formaldehyde solution for 24 hours and embedded with paraffin. Cutted in $5{\mu}m$ thickness with microtome and stained with hematoxylin and eosin (H&E) and TUNEL immunohistochemical stain, and examined histologically under a light microscope. All data were presented as mean ${\pm}SD$, calculating the ratio of normal or atretic follicles to total ovarian follicles. Statistical analysis was performed by the Mann Whitney test using the SPSS ver 19.0. Ratio of atretic to total follicles of 2 Gy group was significantly higher than control or 2 cGy groups (p<0.05). Ratio of normal to total follicles of 2 Gy group was significantly lower than control group in preantral follicle (64.0 vs. 87.7, p=0.027). Ratio of normal to total follicles of 2 cGy group was significantly increased more than control or 2 Gy groups in antral follicle, and there were no significant difference between control and 2 Gy groups (p=0.522). Radiation dose of 2 Gy for cancer radiotherapy have a significant effect on ovarian follicle atresia in rat.

• Journal of Chest Surgery
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• v.39 no.10 s.267
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• pp.739-748
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• 2006

Background: The purpose of this study is to ascertain the neuroprotective effect of cyclosporin A on the 25-min surgical ischemia model in the spinal cords of rabbits with neuropathological correlation and histoimmunochemical analyses, Material and Method: Thirty-two New Zealand white rabbits were randomly divided into four groups: Rabbits were randomly divided into four groups: the control 12 group (n=8), the control 17 group (n=8), the cyclosporin Cs2 group (n=8), and the cyclosporin Cs7 group (n=8). The 12 group underwent a 25-min aortic cross- clamp without intervention and were sacrificed on the 2nd day postoperatively, while the 17 group underwent a 25- min of aortic cross-clamp without intervention and were sacrificed on the 7th day postoperatively. The Cs2 group received cyclosporin A (25 mg/kg) intravenously 15 min after the 25-min cross-clamp and were sacrificed on the End day postoperatively, while the Cs7 group received cyclosporin A (25 mg/kg) intravenously 15 min after the 25-min cross-clamp and were sacrificed on the 7th day postoperatively. The rabbits underwent 25-min surgical aortic cross-clamp. Neurologic functions were evaluated on the 2nd day and 7th postoperative day using Tarlov scoring system. After scoring neurologic function, all rabbits were sacrificed for histopathologic observation. Result: All rabbits survived the experimental procedure. The values of Tarlov score did not show any differences between the control and cyclosporin groups on the 2nd day. The scores of group Cs7 ($2.75{\pm}0.89$) were significantly higher than those of group 17 ($1.25{\pm}1.39$) on the 7th day (p<0,05). On the histologic exanminations, specimens of the spinal cord showed necrosis and apoptosis. The pathologic scores of group Cs7 ($1,0{\pm}0.53$) was less than those of group 17 ($2.13{\pm}1.36$, p<0.05). TUNEL staing showed apoptosis of the specimen in group 12 and Cs2 but there was no stastically significant difference between groups on the score. There were more overexpression of HSP70 and nNOS in cyclosporine group than in control group. Conclusion: We think that cyclosporin A may decrease neuronal cell death with induced upregulation of HSP70 against 25-min ischemia of the spiral cord in the rabbit.

• Journal of Korean Neurosurgical Society
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• v.29 no.9
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• pp.1215-1221
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• 2000

Objective : The clinical prognosis and biological behavior of atypical and especially malignant meningiomas are well known to be worse than benign meningioma, but the degree of biological aggressiveness in each classical subtypes of benign meningioma is controversy. This study was performed to see whether there is a difference in the proliferative activity between each different histological subtypes of benign meningioma as well as atypical meningioma. Methods : Paraffin-embedded surgical specimens of 27 meningiomas, including two recurrent tumors, were studied to evaluate proliferative activity by immunohistochemical method with monoclonal antibodies to proliferating cell nuclear antigen(PCNA) and MIB-1. The specimens consisted of 8 cases of meningothelial, 9 cases of transitional, 5 cases of fibroblastic subtypes and 5 cases of atypical meningiomas. Results : Mean PCNA labeling indices of meningothelial, transitional and fibroblastic meningiomas were $4.82{\pm}5.10%$, $9.01{\pm}4.25%$ and $5.66{\pm}5.32%$, but that of atypical meningiomas was $27.62{\pm}19.67%$, noting a higher value compared to all three subtypes of benign meningiomas. Mean Ki-67 labeling indices of the above 3 subtypes were $0.43{\pm}0.85%$, $0.44{\pm}1.08%$ and $0.24{\pm}0.18%$, and that of atypical meningiomas was also revealed to be of higher value ($0.84{\pm}0.59%$). PCNA and Ki-67 labeling indices were not statistically different between histological subtypes of benign meningioma(p>0.05), but the differences of both immunolabeling between benign and atypical meningiomas were statistically significant(p<0.05). Conclusion : Immunolabeling of PCNA and Ki-67 in intracranial meningiomas reveals no prognostic difference between meningothelial, transitional and fibroblastic subtypes in classical benign meningiomas by measuring expression of PCNA and Ki-67, but it seems to be helpful in differentiating benign and atypical meningioma, later showing more proliferative activity and biological aggressiveness.

• Parasites, Hosts and Diseases
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• v.29 no.4
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• pp.339-354
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• 1991

Localization and characterization of the antigenic components of sparganum which induced IgG and IsM antibodies in the host were studied by immunohistochemical techniques and SDS-PAGT and Western blotting. The antigen recognized by IgG antibody of rats or mice which were immunised by infection or injection of crude extracts of metacestodes of Spirometra erinacei, was located in the parenchyme of sparganum, especially at the cortex and around the calcareous corpuscles. The immunoreaction was demonstrated not only in the encysted fibrous wall of host but around the arterioles or venules in the connective tissue of host. The antigen recognized by IgM antibody of rats or mice was also observed in the parenchyme of sparganum and in the connective tissue of host. By 5∼20% gradient SDS-PAGE and EIBT, we detected antigenic components by IgG and 1gG antibodies of the rat or mouse immunized by infection or injection of crude extract of spargana. Twenty-three antigenic bands from crude extracts of spargana were recognized by IgG antibody and 15 components by IgM antibody of immunized rats. Out of the bands recognized by IgG and IgM antibodies, 15 were cross-reacted each other. Twenty components of eBlcretory-secretory proteins from spargana were recognized by IgG, and 5 components by IgM antibody of immunized rats. By IgG and IgM antibodies of immunized mice, 16 components of crude extracts were recognized by IgG antibody and 9 components by IgM antibody. Twenty components of excretory-secretory preparation were recognized by IgG antibody and 5 components by IgM antibody. Thirteen components of crude extracts were cross-reacted by IgG antibody of rats and mice.

• Tuberculosis and Respiratory Diseases
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• v.45 no.5
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• pp.962-974
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• 1998

Background: Alteration of p53 tumor suppressor genes is most frequently identified in human neoplasms, including lung carcinoma. It is well known that bcl-2 oncoprotein protects cells from apoptosis. Recent studies have demonstrated that bcl-2 expression is associated with favorable prognosis for patients with non-small cell lung carcinoma. However, the precise biologic role of bcl-2 in the development of these tumors is still obscure. p53 and bcl-2 have important regulatory influence in the apoptotic pathway and thus their relationship is of interest in tumorigenesis, especially lung cancer. Purpose: The author investigated to know the prognostic significance of the expression of p53 and bcl-2 in radically resected non-small cell lung cancer. Method: 84 cases of formalin-fixed paraffin-embedded blocks from resected primary non-small cell lung cancer from 1980 to 1994 at Hanyang University Hospital were available for both clinical follow-up and immunohistochemical staining using monoclonal antibodies for p53 and bcl-2. Results : The histologic classification of the tumor was based on WHO criteria., and the specimens included 45 squamous cell carcinomas(53.6%), 28 adeonocarcinomas(33.3%) and 11 large cell carcinomas(13.1 %). p53 immunoreactivity was noted in 47 cases of 84 cases(56.0%). bcl-2 immunoreactivity was noted in 15 cases of 84 cases(17.9%). The mean survival duration was $64.23{\pm}10.73$ months in bcl-2 positive group and $35.28{\pm}4$. 39 months in bcl-2 negative group. The bcl-2 expression was significantly correlated with survival in radically resected non-small cell lung cancer patients(p=0.03). The mean survival duration was $34.71{\pm}6.12$ months in p53 positive group and $45.35{\pm}6.30$ months in p53 negative group(p=0.21). The p53 expression was not predictive for survival. There was no correlation between combination of the different status of p53 and bcl-2 expression in our study. Conclusions : The interaction and the regulation of new biologic markers, such as those involved in the apoptotic pathway, are complex. bcl-2 overexpression is a good prognostic factor in non-small cell lung cancer and p53 expression is not significantly associated with the prognostic factor in non-small cell lung cancer.

• Pediatric Infection and Vaccine
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• v.14 no.1
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• pp.97-103
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• 2007

Purpose : Lewis antigen has been known to have a role in the attachment of H. pylori to the gastric mucosa, but its expression pattern in children with H. pylori infection is still unclear. The recently described blood group antigen-binding adhesin BabA is known to mediate adherence of H. pylori to Lewis B receptors on gastric epithelium. We investigated the expression of Lewis antigen in gastric mucosa of Korean children with H. pylori infection. Methods : The expression of Lewis A ($Le^a$), B ($Le^b$), X ($Le^x$), and Y ($Le^y$) was evaluated by immunohistochemistry in H. pylori positive biopsy specimens from 35 children (antral gastritis in 30, peptic ulcer in 5) and in H. pylori negative specimens from 19 children. PCR assays for cagA and babA2 gene of H. pylori were performed. Results : We confirmed the expression of $Le^a$ in 60%, $Le^b$ in 97%, $Le^x$ in 100%, and $Le^y$ in 100% of the superficial epithelium of the 35 H. pylori positive children. In H. pylori negative patients, $Le^a$, $Le^b$, $Le^x$, and $Le^y$ expression was 52%, 100%, 89%, and 100%, respectively. The cagA gene was detected in 65% and babA2 gene in 25% of 35 patients. No differences in neutrophil activity and chronic inflammation were found according to the presence of cagA and babA2 genes in H. pylori. Conclusion : $Le^b$, $Le^x$ and $Le^y$ antigen were highly expressed in gastric mucosa of Korean children, but they were not associated with the status of H. pylori infection and the positivity of babA2 gene. Further studies for other mucosal receptors and toxins are needed to define the immune responses to H. pylori infection in gastric mucosa of Korean children.

• Radiation Oncology Journal
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• v.19 no.2
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• pp.181-189
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• 2001

Purpose : Changes in the balance between MMP and TIMP can have a profound effect on the composition in the extracellular matrix (ECM) and affect various cellular functions including adhesion, migration, differentiation of cells, and fibrosis and invasion and metastasis of cancer cells. Radiation therapy is a popular treatment modality for benign and malignant tumor, but the study for radiation effect on MMP and TIMP is scarce. In the current study, we have examined the expression of TIMP in fibrosis-prone (C57BL/6) mice after radiation. Methods and Materials : Adult female mice of $10\~12$ weeks were used. The whole body were irradiated using a Varian CL-4/100 with 2 and 10 Gy. Immunohistochemical staining was peformed according to Avidin Biotin complex method and evaluated by observing high power field. For TIMP-1, TIMP-2 antibodies, reactivity was assessed in the parenchymal cell and in the stromal cell. The scale of staining was assessed by combining the quantitative and qualiative intensity of staining. Results : TIMP-1 immunoreactivity did not change in lung. But, in liver, TIMP-1 immunoreactivity was localized in cytoplasm of hepatocyte and Kupffer cell. in kidney, TIMP-1 immunoreactivity was localized in cytoplasm of some tubular cell. Temporal variations were not seen. Dose-response relationship was not seen except kidney. TIMP-2 immunoreactivity in lung was a score (++) at 0 Gy and elevated to a score (+++) at 2 Gy. TIMP-2 immunoreactivity was a score (++) in liver at 0 Gy. TIMP-2 immunoreactivity was localized in cytoplasm of hepatocyte and Kupffer cell as same as patterns of TIMP-1 immunoreactivity. The TIMP-2 immunoreactivity in liver was elevated to (+++) at 2 Gy. Immunoreactivity to TIMP-2 in kidney was a score (+++) at 0 Gy and was not changed at 10 Gy. The score of TIMP-2 immunoreactivity was reduced to (++) at 2 Gy. TIMP-2 immunoreactivity was confined to tubules in kidney. Temporal variation of TIMP-2 immunoreactivity was irregular. Dose-response relationship of TIMP-2 immunoreactivity was not seen. Conclusions : Differences between intensity of expression of TIMP-1 and TIMP-2 in each organ was present. Expression of TIMP was localized to specific cell in each organ. Irradiation increased TIMP-1 immunoreactivity in the liver and the kidney. Irradiation increased TIMP-2 immunoreactivity in the lung. But, in the liver and the kidney, TIMP-2 expression to radiation was irregular. Temporal variation of TIMP-2 immunoreactivity was irregular. Dose-response relationship of TIHP-2 immunoreactivity was not seen. In the future, we expect that the study of immunohistochemical staining of longer period of postirradiation and quantitative analysis using western blotting and northern blotting could define the role of TIMP in the radiation induced tissue fibrosis.

• Development and Reproduction
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• v.14 no.4
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• pp.287-295
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• 2010

It was recently reported that nesfatin-1/NUCB2, which is secreted from the brain, controls appetite and energy metabolism. The purpose of this research was to confirm whether or not the protein and its binding site should have been expressed in the mouse reproductive organs and to know the possible effects of nesfatin-1 on the reproductive function. Using the ICR female mouse ovary and uterus, the expression of NUCB2 mRNA was confirmed with the conventional PCR and the relative amount of NUCB2 mRNA in the tissues was analyzed with real-time PCR. Immunohistochemical staining was performed using the nesfatin-1 antibody to investigate the nesfatin-1 protein expression and the biotin conjugated nesfatin-1 to confirm the binding site for nesfatin-1 in the ovary. Furthermore, in order to examine if the expression of NUCB2 mRNA in the ovary and uterus is affected by gonadotropin, its mRNA expression was analyzed after PMSG administration into mice. As a result, the expression level of NUCB2 mRNA in the ovary and the uterus was as much as the expression level in hypothalamus. As a result of the immunohistochemical staining, nesfatin-1 proteins were localized at the theca cells, the interstitial cells, and some of the luteal cells. However, the granulosa cells in the follicles did not stain. Interestingly, the oocytes in the some follicles were stained with nesfatin-1. On the other hand, nesfatin-1 protein binding sites were displayed at the theca cells and the interstitial cells near the tunica albuginea. After PMSG administration the expression level of NUCB2 mRNA was increased in the ovary and the uterus. These results demonstrate that for the first time the nesfatin-1 and its binding site were expressed in the ovary and NUCB2 mRNA expression was controlled by gonadotropin, suggesting an important role in the reproductive organs as a local regulator. Therefore, further study is needed to elucidate the functions of nesfatin-1 on the reproductive organs.