• The Korean Journal of Pharmacology
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• v.31 no.1 s.57
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• pp.103-114
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• 1995

Platinum coordination complexes are currently one of the most compounds used in the treatment of solid tumors. However, its use is limited by severe side effects such as renal toxicity. Our platinum-based drug discovery program is aimed at developing drugs capable of diminishing toxicity and improving antitumor activity. We synthesized new Pt (Ⅱ) complex analogue containing 1,2-diaminocyclohexane (dach) as carrier ligand and 1,2-bis(diphenylphosphino) ethane (DPPE) as a leaving group. Furthermore, nitrate was added to improve the solubility. A new series of [Pt(trans-ddach)(DPPE).$2NO_3(PC)$ was synthesized and characterized by their elemental analysis and by various spectroscopic techniques [infrared (IR), $^{13}carbon$ nuclear magnetic resonance (NMR)]. PC demonstrated acceptable antitumor activity aganist P388, L-1210 lymphocytic leukemia cells and SK=OV3 human ovarian adenocarcinoma cells, and significant. activity as compared with that. cisplatin. The toxicity of PC was found quite less than thar of cisplatin using MTT, $[^3H]$ thymidine uptake and glucose consumption tests in rabbit proximal tubule cells, human kidney cortical cells and human renal cortical tissues. Based on these results, this novel platinum compound represent a valuable lead in the development of a new anticancer chemotherapeutic agent capable of improving antitumor activity and low toxicity.

• Tuberculosis and Respiratory Diseases
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• v.68 no.1
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• pp.1-5
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• 2010

Background: To analyze the result of $^{18}F-FDG$ positron emission tomography (PET) in patients with a concomitant malignancy and tuberculoma in a tuberculosis (TB)-endemic area. Methods: Twelve patients with a concomitant malignancy and tuberculoma, who underwent whole-body $^{18}F-FDG$ PET, were evaluated retrospectively. The maximal standardized uptake values (SUVmax) of the malignancy and tuberculoma were compared. In 6 patients, $^{18}F-FDG$ PET was repeated during the anti-TB treatment and the changes in SUVmax were analyzed. Results: Of the 12 patients, 10 were male. The mean age was $67.2{\pm}7.9$ years. Tuberculomas were located in the lung (n=10) and lymph nodes (n=2), and tumors were located in the lung (n=6), colon (n=3), stomach (n=1), ovary (n=1) and liver (n=1). Although the mean SUVmax of malignant lesions was higher than that of tuberculomas ($5.2{\pm}3.2$ vs $3.5{\pm}2.0$), the difference was not significant. In 4 patients, the SUVmax was higher in the tuberculoma than the tumor. After anti-TB treatment in 6 patients, the mean SUVmax of the tuberculomas decreased significantly, from $3.5{\pm}2.0$ to $1.6{\pm}0.9$ (p=0.028). Conclusion: In patients with a concomitant malignancy and tuberculoma, SUVmax alone could not differentiate between them. However, $^{18}F-FDG$ PET may be useful in monitoring the response to anti-TB treatment.

• Tuberculosis and Respiratory Diseases
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• v.65 no.1
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• pp.52-56
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• 2008

Sarcoidosis is a systemic granulomatous disease that primarily affects the lung and lymphatic system of the body. Since Brincker first noted a statistically significant increase of malignant tumors among sarcoidosis patients, there have been several reports on simultaneously developed sarcoidosis and malignancy. A 30-year-old man was admitted to our hospital because of multiple enlarged mediastinal lymph nodes. The patient had been well until approximately 10 days before admission, when he developed a cough. Chest X-ray and computed tomography (CT) of the chest that were performed at the outpatient department revealed multiple enlarged mediastinal lymph nodes. Cervical lymph node biopsy revealed both non-caseating granuloma and metastatic papillary carcinoma, whereas the mediastinal lymph node showed only non-caseating granuloma. The thyroid gland surgical specimen showed papillary carcinoma. We report here on a case of a 30-year-old man who had sarcoidosis and thyroid cancer, and we include a review of the literature.

• Investigative Magnetic Resonance Imaging
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• v.11 no.2
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• pp.127-132
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• 2007

Sinonasal neuroendocrine carcinoma is a rare disease, and reports focusing on the MR imaging findings of sinonasal neuroendocrine carcinoma are extremely rare. Threrefore we intend to report 2 cases of histologically confirmed neuroendocrine carcinoma. A 62-year-old man and a 74-year-old man are both presented with nasal bleeding. Computed tomography(CT) images of the 2 patients showed large, ill-defined masses in sinonasal cavities with adjacent bony destructions. MR images showed masses with isosignal intensity on Tl-weighted images and mixed iso- and high signal intensity on T2-weighted images. Post-contrast MR images showed heterogenous enhancement of masses with necrosis. Adjacent bony destructions were also noted on MR images. In both cases, peritumoral cystic lesions or mucoceles with high signal intensity on T1-weighted images were noted in sphenoid sinus. Both of the CT and MR imaging findings of the 2 patients were nonspecific which are usually seen in malignant tumor. But further study is needed for the significance of the peritumoral cystic areas adjacent the tumors.

• Archives of Reconstructive Microsurgery
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• v.9 no.2
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• pp.139-146
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• 2000

The aim of this study was to assess whether the functional regeneration of a lyophilized autografted cartilage could be improved by implanting a vascularized muscle flap into the medullary canal of autografted proximal humerus. A hemijoint reconstruction using a lyophilized osteochondral autograft in proximal humerus was done in 4 rabbits for control, and combined with an vascularized intramedullary muscle flap in another 4 rabbits for the experimental group. Graft healing and the repair process of osteochondral graft were followed by serial radiographs and histologic changes for 9 weeks after experiments. Each two rabbits in control and in experimental group on 5th and 9th week after implantation of hemijoint were sacrified. The results were as follows: 1. All of control and experimental froups on 5th week united solidly on osteotomized site radiologically, but their articular cartilages were destroyed more seriously in the control than that in experimental group with muscle flap on 5th and 9th week after experiment... 2. Histochemically, the cartilage surface are completely destroyed and revealed with severe osteoarthritic changes on all cartilage layers in control, but cartilaginous erosions are mild to moderate and their arthritic changes are also mild with somewhat regeneration of chondrocytes on deep layers more prominetly on 9th week of the experimental group. 3. The amount of collagen and protenized matrix which was determined by Masson-Trichrome stain was markedly decreased that means the weakness of bony strength and low osteogenic potential in lyophilized cartilage. These results suggest that an intramedullary vascularized muscle flap can improve the functional results of lyophilized osteochondral autograft by providing both increased vascularity and populations of mesenchymal cells to initiate new bone formation on osteotomized site as well as the regeneration of deep layers in articular cartilage. In clinical relevances, this lyophilized hemijoint autograft combined with an intramedullary vascularized muscle pedicle graft might be used very effectively for the treatment of malignant long bone tumors to preserve the joint functions, all or partly, and so to replace it with the artificial joint after tumor excision and hemijoint autograft.

• Radiation Oncology Journal
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• v.10 no.2
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• pp.181-186
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• 1992

A retrospective analysis was undertaken for 22 patients with early glottic cancer ($T_1N_0M_0$; 17, $T_2N_0M_0$; 5) who completed curative radiotherapy at the Department of Therapeutic Radiology, Chonnam University Hospital between November 1985 and December 1990. Median follow-up period was 39 months. The 3 year actuarial survival rate of T1, T2 was $81\%$ and $80\%$. respectively. Three patients ($13\%$) showed second malignant tumors and the site of the new primary was esophagus in two patients and lung in the other one. They were excluded from the local control analysis. The local control rate of T1. T2 group was $66\%$ and $50\%$. respectively. The surgical salvage rate and the ultimate local control rate of T1 group was $80\%$ (4/5) and $93\%$. and that of T2 group was $100\%\;(2/2)\;and\;75\%$. respectively. The local control rates of T1 stage were evaluated according to the various parameters. The local control rate of the superficial and exophytic lesion was better than that of the ulcerative and infiltrative one, and the involvement of anterior commissure was not seemed to be adverse prognostic factor. But the protracted treatment time showed the adverse effect on the local control of the disease. All of the eleven patients controlled by primary radiation therapy have maintained their voice well without any significant complication.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.27 no.4
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• pp.289-300
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• 2001

Telomerase is a ribonucleoprotein that synthesizes telomere repeats. It has been reported that activation of telomerase was associtated with immortalization, proliferative activity and carcinogenesis. Recently, telomerase activity has been extensively studied in many kinds of malignant tumors for clinical diagnostic and/or prognostic utilities. In neuroblastoma, breast carcinoma, gastric carcinoma, non-small cell lung carcinoma, close relationship has been reported between high telomerase activity and lymph node metastasis, tumor aggressiveness and poor prognosis. The purpose of this study is to investigate the clinical implication of telomerase activity assay as an adjunctive factor in decision-making on neck node management, speedy pre-operative judging on histologic malignancy grading. Thus we performed semi-quantitative assay of telomerase activity using Telomerase PCR ELISA $kit^{(R)}$(Boeringer Manheim, Germany) and evaluated correlation between telomerase activity and tumor size, neck node metastasis, Anneroth malignancy score and influence of pre-operative chemotherapy on its activity in 27 cases of oral squamous cell carcinomas and 18 cases of normal oral epithelium. Also, correlation between telomerase activities and PCNA indices was evaluated. The results were obtained as follows: 1. The telomerase activities were detected in 24 specimens out of 27 oral squamous cell carcinoma specimens (88.9%) and in 5 specimens out of 18 normal oral epithelium specimens (27.8%). The mean value of telomerase activities was $0.9793{\pm}0.3428$ in 24 oral squamous cell carcinoma specimens and $0.4855{\pm}0.1117$ in 5 normal oral epithelium specimens. The positivity rate and mean value of telomerase activities in oral squamous cell carcinoma specimens were significantly higher than those of normal oral epithelium specimens (p<0.05). 2. There was no significant correlation between total Anneroth malignancy score and telomerase activity (p>0.05), but points of mitosis index and depth of invasion were significantly correlated with telomerase activities (p<0.05). 3. The positive immunohistochemical staining for PCNA(proliferating cell nuclear antigen) was observed in 26 specimens out of 27 oral squamous cell carcinoma specimens and mean value of PCNA indices of 26 specimens was $53.67{\pm}26.46$. PCNA indices were significantly correlated with telomerase activities (p<0.05). 4. The mean value of telomerase activities was significantly higher in pathologic T3/T4 group than in T1/T2 group (p<0.01). There was no significant difference of mean value of telomerase activities between pathologic neck node positive group and negative group (p> 0.05). Pre-operative chemotherapy significantly lowered the telomerase activities (p<0.05). The above results suggested telomerase activity could be used as diagnostic marker and adjunctive parameter for judging on histologic malignancy in oral squamous cell carcinoma.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.32 no.3
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• pp.200-208
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• 2006

Amino acids are required for protein synthesis and energy sources in all living cells. The amino acid transport system L is a major nutrient transport system that is responsible for $Na^+$-independent transport of neutral amino acids including several essential amino acids. In malignant tumors, the L-type amino acid transporter 1 (LAT1), the first isoform of system L, is highly expressed to support tumor cell growth. In the present study, the expression and functional characterization of amino acid transport system L were, therefore, investigated in Saos2 human osteogenic sarcoma cells. RT-PCR and western blot analyses have revealed that the Saos2 cells expressed the LAT1 and the L-type amino acid transporter 2 (LAT2), the second isoform of system L, together with their associating protein heavy chain of 4F2 antigen (4F2hc) in the plasma membrane, but the expression of LAT2 was very weak. The uptakes of [${14}^C$]L-leucine by Saos2 cells were $Na^+$-independent and were completely inhibited by the system L selective inhibitor, 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH). The affinity of [${14}^C$]L-leucine uptake and the inhibition profiles of [${14}^C$]L-leucine uptake by various amino acids in the Saos2 cells were comparable with those for the LAT1 expressed in Xenopus oocytes. The majority of [${14}^C$]L-leucine uptake is, therefore, mediated by LAT1 in the Saos2 cells. These results suggest that the transports of neutral amino acids including several essential amino acids into Saos2 human osteogenic sarcoma cells are for the most part mediated by LAT1. Therefore, the Saos2 human osteogenic sarcoma cells are excellent tools for examine the properties of LAT1. Moreover, the specific inhibition of LAT1 in tumor cells might be a new rationale for anti-tumor therapy.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.32 no.3
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• pp.209-215
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• 2006

Preoperative neoadjuvant chemotherapy using cisplatin and 5-FU is generally given in oral and maxillofacial cancer. At tissue level both inflammation and fibrosis occur after chemotherapy. The cellular changes mimic those of a granulating wound, with activated macrophages and fibroblasts replacing the malignant cells as they are erradicated. Stromal cells, together with extracellular matrix components, provide the microenvironment that is pivotal for tumor cell growth, invasion, and metastatic progression. Vascular endothelial growth factor(VEGF), an important regulator of angiogenesis in cancer, induces mitogenesis of vascular endothelial cells, and vascular permeabilization and microvessel formation in a tumor are associated with tumor nutrition and oxygenation. Also, they are associated with chemotherapeutic drug delivery. Oxygen delivery to tumor appears to rely on a network of microvessels, On the other hand, the tumor microvessel is clearly an important factor in chemotherapeutic drug delivery to cancer cells, and the efficacy of drug delivery can be high in richly vascularized tumors. So, this study was conducted to evaluate the effect of neoadjuvant chemotherapy on microvessel density from 11 patients with tongue cancers. Our results showed that neoadjuvant chemotherapy was seemed to decrease VEGF expression in tumor cells, however, it did not significantly alter VEGF expression in tumor-associated macrophages. Also, Neoadjuvant chemotherapy had little effect on the microvessel density using CD34, and tumor-associated macrophage level using CD68. Thus, tumorassociated macrophages seem to be the key factor associated with the maintenance of microvessel density after neoadjuvant chemotherapy in tongue cancer.

• Journal of Chest Surgery
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• v.20 no.1
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• pp.112-127
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• 1987

Myasthenia gravis is a neuromuscular transmission function disorder characterized by fatigue and weakness of voluntary muscles. This muscular weakness is intensified by activity and stress, and improved by the use of anticholinesterase compounds. It was initially described by Erb in 1879 and later named myasthenia gravis by Jolly in 1895. Although the pathogenesis is Known to be an autoimmune related reduction in the number of available acetylcholine receptors at neuromuscular junctions, the role of thymus in myasthenia gravis is still unclear and under investigation. Thymectomy in the management of myasthenia gravis has become increasingly important since Dr. Blalock observed in 1939 that some patients with thymic tumors and myasthenia gravis improved following thymectomy. A clinical study of 102 cases of myasthenia gravis was performed at Yonsei University College of Medicine. Seoul, Korea from Jan. 1976 to Jun. 1986. In order to determine which factors are of prognostic significance, attention is focused upon pre-operative patient evaluation, problems in operative and post-operative care, and long-term follow-up observations. The results were as follows: 1. The sex distribution was 67 females and 35 males, the mean age of onset was 28.95*1.69 years, and the maximal incidence occurred between 21 and 40 years of age [56 cases: 54.9%]. 2. Clinical manifestations of ocular symptoms were seen to 70 patients [68.6%] extremities weakness in 33 [32.3%], bulbar weakness in 29 [28.4%], and dyspnea in 13 [12.7%]. 3. Study cases more than two thirds were classified as mild types [MG 1 and MG 11A] and 6 cases as grave [MG 1V] based on the modified Osserman`s classification system, 4. Thymectomy was performed in 19 cases which presented in severe myasthenia symptoms and showed no improvement with cholinergic drugs. Histologic examination of the excised thymus glands revealed no abnormalities in 4 cases, thymic hyperplasia in 5, benign thymoma in 5, and malignant thymoma in 5. 5. Immediate post-operative complications included 2 cases of pneumothorax which were treated by tube thoracostomies, there was no operative mortality. 6. The response to cholinergic drugs in 36 cases younger than 20 years old and in 27 cases older than 40 years was relatively poor, while that in 35 cases between the ages of 21 and 40 years old was good. 7. Thirty of 39 cases in groups IIB, III & IV improved markedly with medical or surgical management while only 16 of 59 cases in the mild groups [I and IIA] improved, almost all surgical cases improved in all categories. 8. There were 5 deaths. occurring between 7 months and 3 years 3 months of treatment of myasthenia gravis. The causes of death were myasthenic crisis in 2 cases, respiratory failure due to candidiasis & radiation pneumonitis in one case, cerebral hemorrhage due to high blood pressure in two case.