• Journal of Chest Surgery
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• v.41 no.2
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• pp.149-159
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• 2008

Background: With increasing coronary bypass and peripheral vascular surgeries, the demand for homologous vascular or synthetic conduits has continued to grow, but wide-spread application has been limited by dismal patency rates. Although cryopreserved allograft valves may provide a suitable alternative, current viability or patency of implanted allograft vascular conduits has been unsatisfactory. Material and Method: We serially analyzed the outcomes of canine femoral artery and saphenous vein allograft implants after storage in either $4^{\circ}C\;or\;-170^{\circ}C$. Result: There were no differences in graft flow rate (patency) (p=0.264), rate of thrombosis (p=0.264), presence of endothelium (p=0.587), or immunohistochemical staining for thrombomodulin (p=0.657) were detected between grafts stored in $4^{\circ}C\;and\;-170^{\circ}C$. Greater flow occurred in the arterial grafts versus the venous grafts (p=0.030), irrespective of the preservation method, with a significantly lower incidence of thrombosis (p=0.030) in arterial allografts. There was a correlation coefficient of -0.654 between thrombosis and positive immunohistochemical staining for thrombomodulin (p=0.006) and a correlation coefficient of 0.520 (p=0.0049) between the endothelial presence and positive immunohistochemical staining for thrombomodulin. The relationship between the presence of endothelium and thrombomodulin expression failed to show any correlation within the first 2 weeks (p=0.306). However, a strong correlation was seen after 1 month (p=0.0008). Conclusion: Tissue storage in either $4^{\circ}C\;or\;-170^{\circ}C$ in 10% DMSO/RPMI-1640 preservation solution preserved grafts equally well. In terms of thrombosis and graft patency, arterial grafts were superior to venous grafts. Considering the poor correlation between thrombomodulin expression and the presence of an endothelium in the implanted graft within the first two weeks, grafts in this period would not be thromboresistant.

• Tuberculosis and Respiratory Diseases
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• v.44 no.6
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• pp.1285-1295
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• 1997

Background : EGFR is one of the initial step in signal transduction pathway about multistep carcinogenesis. It is homologous to oncogene erbB-2 and is the receptor for EGF and TGF alpha. EGFR has important role in the growth and differentiation of tumor cells. So, EGFR in non-small cell lung cancer was examined to search for possible evidence as clinical prognostic factor. Methods : To investigate the role of EGFR in lung cancer, the author performed immunohistochemical stain of EGFR on 57 resected primary non-small cell lung cancer specimens. And the author analyzed the correlation between EGFR expression, clinical parameters, Sand $G_1$ phase fraction and survival. Results : 1) EGFR were detected in 56% of total 57 patients (according to histologic type, squamous cancer 50%, adenocarcinoma 63%, large cell cancer 75%) (according to TNM stage, stage I 64%, stage II 38%, stage III 55%) (according to cellular differentiation, well 50%, moderately 52%, poorly 65%). All differences were insignificant 2) Using the flow cytometric analysis, mean S-phase fraction of EGFR (+) and (-) group were 22.3(${\pm}10.5$)%. 18.0(${\pm}10.9$)% (p>0.05), mean $G_1$-phase fraction of EGFR (+) and (-) group were 68.4(${\pm}11.6$)%, 71.1(${\pm}12.8$)%, (p>0.05) 3) Two-year survival rate of EGFR (+) and (-) group were 53%, 84%, median survival time of EGFR (+) and (-) group were 26, 53 months. (p<0.05, Kaplan-Meier, generalized Wilcox) Conclusion : EGFR immunostaining may be a simple and useful method for survival prediction in non-small cell lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.52 no.5
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• pp.453-462
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• 2002

Background : Matrix metalloproteinases(MMPs) are a large family of proteolytic enzymes, which are involved in the degradation of many different components of the extracellular matrix. There is increasing evidence indicating that individual MMPs have important roles in tumor invasion by inactivating the MMPs. In this study, the correlation between MMPs and TIMPs expression, and the clinical outcome was investigated. Materials and Methods : Immunohistochemical staining of MMP-2, 9 and TIMP-1,2 were performed on paraffin-embedded tumor sections from 74 resected primary non-small cell lung cancers. Results : In 74 patients, MMP-2, MMP-9, TIMP-1, and TIMP-2 immunoreactivity was demonstrated in 24(34%), 19(26%) and 32(43%) of the paraffin-embedded tumors, respectively. The median survival of the MMP-2 positive cases was significantly shorter than that of the negative cases(20 vs 34 months). The median survival of the TIMP-2 positive cases was also was significantly longer than that of the negative cases (34 vs 18 months). The MMP-2, and MMP-9 expression level had a positively correlation with a more advanced stage and lymph node metastasis. There was inverse correlation between TIMP-2 expression and tumor invasion. The median survival of the MMP-2 negative/TIMP-2 positive cases was higher than that of the other cases. Conclusion : These results suggest that tumor invasion and lymph node metastasis are closely related to MMP-2 and MMP-9 expression. There was an inverse correlation between TIMP-2 and MMP-9 expression, and tumor invasion.

• Journal of Gastric Cancer
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• v.6 no.4
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• pp.284-290
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• 2006

Purpose: Many previous studies have suggested that cyclooxygenase-2 (COX-2) over expression is closely related to angiogenesis. However, few have reported the relationship between COX-2 and lymphangiogenesis which is still unclear, The aim of this study was to determine the relationship between COX-2 expression and lymphangiogenetic factor, VEGF-C, in human gastric cancer and to correlate COX-2 and VEGF-C expression with other clinocopathological features to investigate whether COX-2 contributes to lymphangiogenesis and enhances lymph node metastasis. Materials and Methods: One hundred patients who underwent curative radical surgery in Hanyang University hospital from July 1998 to June 2001 were selected. The expression of COX-2 and VEGF-C were detected by using immunohistochemistry, and the relationships between these two parameters and several clinicopathological factors (gender, stage, lymph node status, tumor location, Lauren classification and angioinvasion) were determined. Results: Increased COX-2 expression was found in 86 of 100 tumor samples (86%) and in 70 of 100 tumor samples (70%) with VEGF-C. A high correlation between VEGF-C expression and lymph node metastasis was observed (P=0.033) along as well as COX-2 expression (P=0.012). Also, there was a significant correlation between COX-2 and VEGF-C expression (P=0.026), yet no correlation were found between COX-2 and VEGF-C expression and other clinicopathological parameters. Conclusion: Our study suggests that COX-2 expression contributes to lymphangiogenesis by mediating VEGF-C and finally promoting lymph node metastasis.

• Applied Microscopy
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• v.40 no.2
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• pp.53-64
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• 2010

Glutamate receptors may play a critical role in the refinement of developing synapses. The lateral superior olivary nucleus (LSO)-medial nucleus of trapezoid body (MNTB) synaptic transmission in the mammalian auditory brain stem mediate many excitatory transmitters such as glutamate, which is a useful model to study excitatory synaptic development. Hearing deficits are often accompanied by changes in the synaptic organization such as excitatory or inhibitory circuits as well as anatomical changes. Owing to this, circling mouse whose cochlea degenerates spontaneously after birth, is an excellent animal model to study deafness pathophysiology. However, little is known about the development regulation of the subunits composing these receptors in circling mouse. Thus, we used immunohistochemical method to compare the N-Methyl-D-aspartate receptor (NMDA receptor) NR1, NR2A, NR2B distribution in the LSO which project glutamergic excitatory input into the auditory brainstem, in circling mouse of postnatal (p) 7 and 16, which have spontaneous mutation in the inner ear, with wild-type mouse. The relative NMDAR1 immunoreactive density of the LSO in circling mouse p7 was $128.67\pm8.87$ in wild-type, $111.06\pm8.04$ in heterozygote, and $108.09\pm5.94$ in homozygote. The density of p16 circling mouse was $43.83\pm10.49$ in wild-type, $40\pm13.88$ in heterozygote, and $55.96\pm17.35$ in homozygote. The relative NMDAR2A immunoreactive density of LSO in circling mouse p7 was $97.97\pm9.71$ in wild-type, $102.87\pm9.30$ in heterozygote, and $106.85\pm5.79$ in homozygote. The density of LSO in p16 circling was $47.4\pm20.6$ in wild-type, $43.9\pm17.5$ in heterozygote, and $49.2\pm20.1$ in homozygote. The relative NMDAR2B immunoreactive density of LSO in circling mouse p7 was $109.04\pm6.77$ in wild-type, $106.43\pm10.24$ in heterozygote, and $105.98\pm4.10$ in homozygote. the density of LSO in p16 circling mouse was $101.47\pm11.5$ in wild-type, $91.47\pm14.81$ in heterozygote, and $93.93\pm15.71$ in homozygote. These results reveal alteration of NMDAR immunoreactivity in LSO of p7 and p16 circling mouse. The results of the present study are likely to be relevant to understand the central change underlying human hereditary deafness.

• Tuberculosis and Respiratory Diseases
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• v.40 no.1
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• pp.23-28
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• 1993

Background: Since an important component of carcinogenesis is unregulated growth, many investigators have reported the methods to detect cell proliferation in tissues including PCNA. PCNA is a 36 Kd intranuclear polypeptide and plays a critical role in cell proliferation. Thus progressive dysregulation of proliferation during carcinogenesis can be directly visualized in the paraffin embedded tissue using immunohistochemistry for PCNA which has an advantage of simplicity and maintenance of tissue architecture. The heterogeneity of PCNA expression is known to be related with proliferating fraction, histologic grade, DNA ploidy, and susceptibility of anticancer drugs, etc. We analyzed the biologic significance of the expression of PCNA in lung cancer tissues. Method: 43 lung cancer tissues, which were resected by surgery and were embedded in paraffin, were stained immunohistochemically by one hour MicroProbe System and the results were corelated with cell type, stage, site and survival. Result: 1) Suamous cell type showed high positivity (89%) than in adenocarcinoma (54%). 2) No significant difference related to tumor stage was noticed. 3) No significant difference between primary site and metastatic site was noticed. 4) No significant difference in 12-month survival between positive group and negative group was noticed. Conclusion: From this study, we concluded that imunohistochemistry for PCNA expression of routinely processed tissue is a simple technique for the assessment of proliferation in non-small cell lung cancer. Whether the labelling index has an independent prognostic value and deserves special attention in pathobiological evaluation in lung cancer remains to be investigated from large series with longer follow-up and to be correlated with multiple biological markers.

• Journal of Chest Surgery
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• v.36 no.10
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• pp.711-720
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• 2003

Bakground : Complete resection by the surgery has been selected as the treatment of choice in lung cancer patients, but in cases of recurrence after excision or inoperable cases, the importance of anticancer chemotherapy has been emphasized. If one can select a set of the sensitive chemotherapeutic agents before anticancer chemotherapy, it will give more favourable results. Subrenal capsular assay has been recognized as a useful in-vivo chemosensitivity test of thoracic and abdominal tumors and it can be done in a short time for a rapid interpretation of tumor responsiveness to anticancer chemotherapeutic drugs. It has been reported that various kinds of cancer cells can be implantable to the kidney, but so far there is no comparative study of xenogeneic cell implantation on liver, spleen and kidney. The author implanted the human lung cancer cells under the capsule of S.D rat's liver, spleen and kidney respectively and compared the pattern of growth and histology. Material and Method: After incubation of human lung cancer cell line (SW-900 G IV) in RPMI 1640 (Leibovitz L-15 medium) culture media, 3${\times}$3${\times}$3 mm size fibrin clots which contain 108 cancer cells were made. Thereafter the fibrin clots were implanted at subcapsule area of liver, spleen and kidney of S.D. female rat. For immune suppression, cyclosporin-A (80 mg/Kg) was injected subcutaneously daily from post-implantation first day to sixth day. The body weight was measured at pre and post implantation periods. The growth pattern and the size of tumor mass were observed and the pathologic examination and serum tumor marker tests were performed. Result: Body weight increased in both of control and experimental groups. Serum Cyfra 21-1 was not detected. Serum levels of CEA and NSE revealed no significant change. The SCC-Ag increased significantly in implanted group. The growth rate of human lung cancer cells which was implanted on spleen was higher than on liver or kidney. The surface area, thickness, and volume of tumor mass were predominant at spleen. The success rates of implantation were 80% on kidney, 76.7% on spleen and 43.3% on liver. Pathologic examination of implanted tumors showed characteristic findings according to different organs. Tumors that were implanted on kidney grew in a round shape, small and regular pattern. In the spleen, tumors grew well and microscopic neovascularization and tumor thrombi were also found, but the growth pattern was irregular representing frequent daughter mass. Human lung cancer cells that were implanted in the liver, invaded to the liver parenchyme, and had low success rate of implantation. Microscopically, coagulation necrosis and myxoid fibrous lesion were observed. Conclusion: The success rate of implantation was highest in the kidney. And the mass revealed regular growth that could be measured easily. The SCC-Ag was presented earlier than CEA or Cyfra21-1. The Cyfra21-1 was not detected at early time after implantation. The best model for tumor implantation experiment for chemosensitivity test was subrenal capsular analysis than liver and spleen and the useful serum tumor marker in early period of implantation was the SCC-Ag.

• The Journal of Korean Obstetrics and Gynecology
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• v.33 no.3
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• pp.95-118
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• 2020

Objectives: The objective of this in vivo study is to observe the analgesic effects or improvements of Gyejibokryeong-hwan aqueous extracts (GJBRHe) on the Primary dysmenorrhea (PD) in rats as compared to those of Indomethacin (IND). Methods: The rats were administered with estradiol benzoate for 10 days and oxytocin 1 hour after the last 10th administration of estradiol benzoate to make the primary dysmenorrhea rat model. Gyejibokryeong-hwan aqueous extracts 500, 250 and 125 mg/kg were orally administrated, for 10 days once a day. Then the changes on the body weights and gains during experimental periods, uterine weights and gross inspections, abdominal writhing response for analgesic activities, uterus lipid peroxidation (malondialdehyde (MDA) levels), antioxidant defense system - glutathione (GSH) contents, activities of superoxide dismutase (SOD) and catalase (CAT), Nuclear factor-κB (NF-κB) and Cyclooxygenase (COX)-2 mRNA expressions, were monitored with uterus histopathology and immunohistochemistry for tumor necrosis factor (TNF)-α and inducible nitric oxide synthase (iNOS). The results of Gyejibokryeong-hwan aqueous extracts were compared to those of Indomethacin adminstered rats. Results: As results of estradiol benzoate and oxytocin treatment, noticeable decreases of body weights and gains, uterus GSH contents, SOD and CAT activities, increases of abdominal writhing responses, uterus lipid peroxidation (MDA level), uterus weights, NF-κB and COX-2 mRNA expressions were observed with increases of TNF-α and iNOS immunolabeled cells, inflammatory cell infiltrations, congestion and enlargement of the uterus at gross and histopathological inspections. These means classic inflammatory and oxidative stress mediated primary dysmenorrhea are relatively well induced. However, these signs were favorably and dose-dependently inhibited by administration of three different dosages of Gyejibokryeong-hwan aqueous extracts, but lesser than those of Indomethacin. Conclusions: The results obtained in this study suggest that Gyejibokryeong-hwan aqueous extracts has favorable analgesic and refinement activities dose-dependently on the estradiol benzoate and oxytocin treatment-induced primary dysmenorrhea signs.

• Tuberculosis and Respiratory Diseases
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• v.42 no.2
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• pp.142-148
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• 1995

Background: Despite modern diagnostic, staging, and therapeutic advances, esp. with molecular biologic techniques, the 5-year survival rate of all cases of lung cancer does not exceed 15%. Also, the incidence of lung cancer of both sex in Korea is increasing year by year and the lung cancer is one of the leading causes of cancer death. Therefore, it is strongly needed to develop the new combination of treatment modalities including neoadjuvant chemotherapy and to identify tumor specific characteristics with staging or prognostic markers. Here we present the clinical significance of several biologic tumor markers to use as a prognostic markers in patients with non-small cell lung cancers. Method: The survival has correlated with the expressibility of proliferative cell nuclear antigen (PCNA), epidermal growth factor receptor(EGFR), p53 and/or blood group antigen A(BGAA) using immunohistochemistry in 46 patients with non-small cell lung cancers. Results: 1) The expression rates of PCNA, EGFR, p53 and BGAA were 80.6%, 61.3%, 45.9% and 64.3%, respectively and those were not correlated to cell types or clinical stges. 2) The expression of BGAA was correlated with better survival in median survival and in 2-year survival rate and that of PCNA was correlated with worse survival in median survival and 2-year survival rate. 3) The expression of EGFR or p53 was not valuable to predict prognosis in non-small cell lung cancers. 4) With simultaneous applications of PCNA, EGFR and p53 immunostain, the patients with 2 or more negative expressions showed better prognosis than the patients with 2 or more positive expressions. Conclusion: It is suggested that the expression of blood group antigen may be a positive prognostic factor and that of PCNA may be a negative prognostic factor. Also, the combination of expressions of PCNA, EGFR and p53 may be used as a negative prognostic factor.

• Development and Reproduction
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• v.11 no.3
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• pp.245-251
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• 2007

Vinclozolin(VCZ), a systemic dicarboximide fungicide, has been used in the control of diseases caused by microorganism of some species in fruits, vegatables and ornamental plants. Although VCZ itself is a very weak antagonist for androgen receptor binding, both melabolites M1 and M2 are effective antagonists. The present study was undertaken to examine whether prepubertal exposure to VCZ affects on the onset of puberty and the associated reproductive parameters such as hormone receptor expressions in female rats. VCZ(10 mg/kg/day) was administered daily from postnatal day 21(PND 21) through the day when the first vaginal opening(V.O.) was observed. Gross anatomy and weight of reproductive tissues were compared to test the VCZ's effects on the cell proliferation. Furthermore, histological studies were performed to assess the structural alterations in the tissues. To determine the transcriptional changes in progesterone receptor(PR), total RNAs were extracted and applied to the semi-quantitative reverse transcription polymerase chain reaction(RT-PCR). As a result, delayed V.O. was shown in the VCZ group(PND $34.00{\pm}1.22$) compared to the control group(PND $38.20{\pm}1.92$; p<0.01). VCZ treatment significantly decreased the wet weight of ovaries and uteri compared to the control group(p<0.01). Graafian follicles and corpora lutea were observed only in the ovaries from the control animals, while numerous primary, secondary follicles and small atretic follicles were observed in the ovaries from VCZ group. Similarly, hypotrophy of luminal and glandular uterine epithelium was found in the VCZ group. In the semi-quantitative RT-PCR studies, the transcriptional activity of PR in ovary(p<0.01) from VCZ group were significantly lower than those from the control group while in uterus were similar compared with the control group. The present studies demonstrated that the acute exposure to VCZ during the critical period of prepubertal stage could inactivate the reproductive system resulting delayed puberty in female rats.