• 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.

• Tuberculosis and Respiratory Diseases
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• v.48 no.5
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• pp.757-765
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• 2000

Background : Angiogenesis plays a critical role in human tumor growth and metastasis. Microvessel count as a measure of tumor angiogenesis, has been significantly correlated with invasive and metastatic patterns in breast. prostate and cutaneous carcinomas. Materials and Methods : Fifty patients with curatively resected non-small cell lung cancer were evaluated. Tumor tissues embedded in paraffin block were stained by anti CD 31 (PECAM, platelet endothelial cellular adhesion molecule) using immunohistochemical method to assess microvessel count. Microvessels were counted in the most active areas of neovascularization(microscopy, 200$\times$). Results: 1) Mean microvessel count was 47.1$\pm$17.7(per 200$\times$field) in total 50 cases. 2) Mean microvessel count of adenocarcinoma (54.4$\pm$19.9) was significantly higher than that of squamous cancer (43.9$\pm$16.2) (p<0.05), but there were no relationship between microvessel count and TNM stages. 3) Median survival time, 2-year and 5-year survival rates of the low microvascular group (microvessel count<45, 22 cases) were 61 months, 80% and 40%, respectively, and those of the high microvascular group(microvessel count$\geq$45, 28 cases) were 46 months, 75% and 12%, respectively. As results, prognosis of low microvascular group is statistically significantly superior to that of the high microvascular group (p=0.0162, Kaplan-Meier, log-rank). Conclusion : Angiogenesis assessed by microvessel count can be used as one of the significant prognostic factors in non-small cell lung cancer.

• Journal of Chest Surgery
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• v.40 no.5 s.274
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• pp.329-340
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• 2007

Background: Matrix Metalloproteinase (MMP) inhibition has emerged as a potential therapeutic strategy for the left ventricular dilatation that occurs after myocardial infarction. This study is designed to evaluate which treatment is better for attenuating the left ventricular remodeling via MMP inhibition 1) during the early, short highly MMP producing period of the initial phase or 2) during most of the period of the initial phase after myocardial infarction. Material and Method: Myocardial infarction was induced by ligation of the left anterior descending coronary artery in rabbits. The experimental group was divided into 3 groups. The myocardial infarction only (MI only) group consisted of 7 cases. The MMP inhibitor administered for 5 days after MI (MMPI 50) group had 6 cases, and these rabbits were given MMP inhibitor for 5 days after myocardial infarction, beginning with the postoperative first day. MMP inhibitor administered for 9 days (MMPI 90) group consisted of 5 cases and these rabbits were given MMPI for 9 days the same manner as above. CG2300 was used as a selective MMPI; this is a potent MMP-2 and -9 inhibitor Two-D echocardiograms were performed on all the groups at the time of preoperative period, the post-operative 1st week, the postoperative 20 week and the postoperative 30 week, and we measured the end-diastolic dimension (EDD), the end-systolic dimension (ESD), and the ejection fraction (EF). Result: The echocardiograms generally showed postoperative left ventricular dilatation in the MI only group. The EDD was increased significantly higher in the postoperative 1 week compared to the preoperative value (p<0.05). The ESD was also increased significantly higher in the postoperative 1st week, the postoperative 20 week and the postoperative 30 week compared to the preoperative value (p<0.05). Left ventricular dilatation was noted to be less In the MMPI 9d group than in the MI only and MMPI 5d groups. In the MMPI 9d group, there was no significant change of EF postoperatively compared to the preoperative period. MMP-2 and MMP-9 were measured from the infarcted myocardial tissue at post-MI 4 weeks by performing western blotting and zymography. The changes the of protein expression and activity of MMP-2 and MMP-9 were not significant in the three MI groups and the normal heart group. Histopathologic examination revealed severe collagen deposition in the MI only group. Collagen accumulation was reduced in both the MMPI groups. The MMPI 9d group revealed an increased number of capillaries. Conclusion: Left ventricular dilatation developed rapidly after, MI from ligation of the coronary artery and MMPI attenuated the ventricular dilatation. The effect of MMPI seemed to have better a result from its usage during most of the period of the initial phase after myocardial infarction. This suggested that increased neovascularization by MMPI may also contribute to attenuation of the left ventricular remodeling.

• Journal of The Korean Ophthalmological Society
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• v.59 no.12
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• pp.1142-1151
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• 2018

Purpose: We assessed the visual and anatomical outcomes, and the safety profile of long-term intravitreal anti-vascular endothelial growth factor (VEGF) injections (aflibercept, ranibizumab, and bevacizumab) given to treat neovascular age-related macular degeneration (NAMD). Methods: We analyzed medical records collected over 7 years of treatment-naive NAMD patients who received outpatient clinic-based intravitreal anti-VEGF injections. All were treated employing either "treat-and-extend" or "as needed" protocols at the discretion of the retinal specialist. The number of injections, adverse events associated with injection, and measures of visual acuity (VA), central foveal thickness (CFT), and intraocular pressure (IOP) were recorded. Results: Overall, we assessed 196 eyes of 196 patients (average age $68.6{\pm}9.6years$; 77 females). Patients received an average of $17.3{\pm}13.5$ injections over $78.0{\pm}16.5months$ of clinical follow-up. The initial mean VA (logMAR) was $0.75{\pm}0.58$ and the CFT was $349.7{\pm}152.6{\mu}m$. Both parameters exhibited maximal improvements at the 6-month visit (p < 0.05). However, the clinical outcomes worsened over the 7-year clinical course; the best-corrected visual acuity (BCVA) was $0.91{\pm}0.78$ and the CFT was $284.5{\pm}105.8{\mu}m$ at 7 years. The BCVA at 7 years was significantly correlated with the initial BCVA. IOP-related events increased 11-fold and anterior chamber reactions increased 3-fold over the years, but no significant complications such as endophthalmitis were recorded. Conclusions: The use of intravitreal anti-VEGF agents was associated with initial visual improvements over 6 months but did not prevent the worsening of NAMD over 5 years. The BCVA at the initial visit was a strong predictor of the final BCVA. A more intensive injection schedule might improve long-term outcomes.