• The Journal of the Korean bone and joint tumor society
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• v.20 no.1
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• pp.7-13
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• 2014

Purpose: As well as patient survival, the restoration of postoperative function such as ambulation is important in limb salvage operations for treatment of malignant bone tumors involving the proximal femur. The authors analyzed clinical outcomes of limb salvage operations using tumor prostheses for metastatic or primary malignant bone tumors in the proximal femur. Materials and Methods: From February 2005 to January 2014, 20 cases (19 patients) with malignant bone tumor involving the proximal femur with pain or complicated pathologic fracture were treated with segmental resection and limb salvage operations with tumor prostheses. Mean age was 63.1 years (range 35-86). Fourteen patients were male and six ones were female. The mean follow-up period was 20 months (1-94 months). There were 15 cases of metastatic bone tumor, 4 cases of osteosarcoma, and 1 case of multiple myeloma. The primary tumors of the metastatic bone tumors included 4 lung cancers, 3 hepatocellular carcinomas, and 3 renal cell carcinomas. Other primary tumors were breast cancer, thyroid cancer, colon cancer, prostate cancer, and malignant spindle cell tumor, each in 1 case. Modular tumor prostheses were used in all cases; (Kotz's$^{(R)}$ Modular Tumor prosthesis (Howmedica, Rutherford, New Jersey) in 3 cases, MUTARS$^{(R)}$ proximal femur system (Implantcast, Munster, Germany) in 17 cases). Perioperative pain was assessed with Visual Analogue Scales (VAS). Postoperative functional outcome was assessed with Musculoskeletal Tumor Society (MSTS) grading system. Results: Out of 20 cases (19 patients), 11 cases (10 patients) survived at the last follow-up. Average postoperative survival of the 9 deceased patients was 10.1 months (1-38 months). VAS score improved from pre-operative average of 8.40 (5-10) to 1.35 (0-3) after operation. Average postoperative MSTS function score was 19.65 (65.50%, 7-28). The associated complications were 2 local recurrences, 3 hematomas, 3 infections, 2 scrotal swellings, and 1 dislocation. There was no case of periprosthetic fracture or loosening. Conclusion: Limb salvage operation with tumor prosthesis is an appropriate treatment for early pain reduction and functional restoration in malignant bone tumors in the proximal femur with pain an/or complicated pathologic fractures.

• Journal of Oral Medicine and Pain
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• v.24 no.2
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• pp.145-161
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• 1999

The proto-oncogene bcl-2 confers a survival advantage to cells by blocking programmed cell death (apoptosis). Overexpression of bcl-2 probably plays a role in tumorigenesis, and the expression of the bcl-2 protein has been investigated in many kinds of tumors. An increased expression of nitric oxide synthetase(NOS) has been observed in human colon cancer cell lines as well as in human gynecological, breast, and CNS tumors. However there have been only a few reports on the expression of bcl-2 and $NOS_2$ in oral white lesions and cancer. The aim of this study was to investigate the relationship between the expression of Bcl-2 and $NOS_2$ and several pathological parameters such as histological types and layers. We reported desregulation of bcl-2 and $NOS_2$ expression during progression from oral white lesion, lichen planus and leukoplakia to squamous cell carcinoma. The obtained results were as follows: 1. Immunohistochemical analysis with monoclonal antibodies to bcl-2 oncoprotein and $NOS_2$ in formalin-fixed paraffin-embedded tissue sections revealed that bcl-2 expression is restricted to the basal cell layer and $NOS_2$ was mild expressed only in subepithelial inflammatory cells in normal human mucosa. There wasn't specific finding of those in lichen planus and leukoplakia. 2. Bcl-2 immunoreactivity in severe epithelial dysplasia or CIS occurs throughout the epithelium, $NOS_2$ reactivity in most superficial layer were noted. 3. In well-differentiated squamous cell carcinomas, mostly bcl-2 was overexpressed. In moderated and poor squamous cell carcinomas, the expression of $NOS_2$ was increased and that of bcl-2 was decreased. 4. The immunoreactivity of bcl-2 was 12.5% of normal mucosa, 30% of leukoplakia, 44% of lichen planus and 67% of carcinoma in situ. In carcinoma, those were 43%, 50% and 67% according to differentiation, respectively. 5. The immunoreactivity of $NOS_2$ was 25% of normal mucosa, 70% of leukoplakia, 78% of lichen planus and 100% of carcinoma in situ and epithelial dysplasia. In carcinoma, those were higher in moderated(100%) and poor(83%) squamous cell carcinomas than in well differentiated type(71%). 6. The expression of bcl-2 and $NOS_2$ by Western blot was increased highly in lichen planus and leukoplakia. Therefore, the expression of bcl-2 was increased in the white and precancerous lesions and that was decreased by differentiation of carcinoma. However, $NOS_2$ immunoreactivity in carcinoma in situ was lower than those in moderated and poor squamous cell. These findings suggest that the interaction of bcl-2 and $NOS_2$ may be roled importantly in growth and development of carcinoma.

• Korean Journal of Medicinal Crop Science
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• v.18 no.3
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• pp.157-167
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• 2010

We investigated a method to improve anticancer activities of Acer mono wood extracts by ultra high pressure extraction process. The A. mono was extracted by water at $40^{\circ}C$ and 300 MPa for 15 min (High Pressure Extraction, HPE). The extraction yield by ultra high pressure extraction process was 5.42%. The cytotoxicity on human normal lung cell (HEL299) of the extracts from HPE showed 21.54% lower than that from conventional water extraction at $100^{\circ}C$ in adding the maximum concentration of 1.0 mg/$m{\ell}$. Ultra high pressure extracts process for 15 minutes extracts (HPE15) showed more potent scavenging effect than the control, BHA. On SOD-like test, the HPE15 showed highest activity as 32.4% at 1.0 mg/$m{\ell}$ concentration. Human stomach adenocarcinoma, liver adenocarcinoma, breast adenocarcinoma and lung adenocarcinoma cell growth were inhibited up to about 67~79%, in adding 1.0 mg/$m{\ell}$ of extracts from HPE. HPE was 20~25% higher than conventional water extraction. It was interesting that, among several cancer cell lines (stomach adenocarcinoma, liver adenocarcinoma), the growth of digestive related cancer cells were most effectively inhibited as about 75~79%. On in vivo experiment using ICR mice, the variation of body weight of mice group treated A. mono wood extracts from HPE of 100 mg/kg/day concentration was very lower than control and other group. The survival times of group treated this extracts was 61.96% longer than that of the control group and this extracts showed the lower tumor weight, which were 10.49 g than positive control as 16.17 g. Based on these results, we could tell that the HPE wood extracts of A. mono had higher anticancer activity than conventional water extraction. The results of HPE showed obvious advantages in higher efficiency, shorter extraction time, at lower energy costs.

• Journal of Life Science
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• v.34 no.6
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• pp.434-441
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• 2024

Mammary gland tumors are the most common tumors detected in non-spayed female dogs and pose a significant clinical challenge. Due to the strong similarity between canine mammary tumors (CMT) and human breast cancer (HBC), biomarkers identified in HBC can also be detected in CMT. These biomarkers have been shown to offer valuable insights into early diagnosis, prognosis, and treatment strategies. The purpose of this article is to provide a concise overview of CMT biomarkers based on the current literature. Traditional treatments for CMT in dogs typically begin with surgery, followed by chemotherapy, radiotherapy, or hormonal therapy. However, these treatments alone are not always fully effective. A diagnostic biomarker can detect the presence of a disease or the characteristics of a disease and classify an individual's status. Prognostic biomarkers focus on predicting the expected progression, recurrence, or survival of the disease in patients. By utilizing advances in understanding the mechanism of canine-specific mammary gland tumors, the estimation of biomarkers offers hope for improved outcomes in cancer patients. Novel technologies, such as single-cell RNA sequencing analysis, could provide a valuable resource for deciphering intra- and inter-tumoral heterogeneity. This review paper explores current research on CMT biomarkers and suggests directions for their development.

• Tuberculosis and Respiratory Diseases
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• v.45 no.3
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• pp.565-573
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• 1998

Malignant pleural effusions are most commonly associated with lung cancers, however, it also can be resulted from breast cancers, ovarian cancers, stomach cancers and so on. According to the their histologic types, adenocarcinoma have been known as the most common cell type of malignant pleural effusions and squamous cell carcinoma is rare. We herein present incidences, clinical characteristics and survivals of malignant pleural effusions according to their cell types and primary diseases. The objects are 84 malignant pleural effusion patients diagnosed by pleural fluid cytologic examination or pleural biopsy from Jan. 1992 to May. 1997 in Seoul National University Hospital. A retrospective chart review on their histologic types, biochemical parameters and survivals is described. Among 84 patients, 52 were males and the other 32 were females with 1.6:1 of male and female ratio and their mean age was 57.6 years old. Common symptoms of them wele dyspnea, cough, sputum and pleuritic chest pain. The proportions of bloody nature of effusion, lymphocyte dominant pleural effusion, exudative effusions were 66%, 39% and 93%, respectively. They consisted of 54 cases of adenocarcinoma(33 cases of them were lung cancers), and 10 cases of squamous cell carcinoma (8 cases of them were lung cancers), 10 cases of malignant lymphoma, 8 cases of small cell lung cancer and a case of mesothelioma and leukemia. There was no differences in characteristics of effusions, clinical features and survivals between each histologic cell types. Analyzing them according to primary diseases, no difference except longer survivals in malignant pleural effusions from breast cancer than from other cancers was observed. In conclusion, considering the incidences of histologic types of lung cancers during same period (squamous cell carcinoma; 47%, adenocarcinoma; 33%, small cell lung cancer; 12% and large cell carcinoma; 2%), malignant pleural effusions more likely occurred in adenocarcinoma than other cell types of lung cancers and there was no significant difference of clinical characteristics between histologic types.

• Tuberculosis and Respiratory Diseases
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• v.49 no.1
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• pp.60-71
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• 2000

Backgrounds : Cathepsin D, an aspartic lysosomal proteinase, is believed to be involved in local invasion and metastasis of tumor cells by its proteolytic activity and has been described to be associated with tumor progression and prognosis in some human malignancies including breast cancer. But, its prognostic value for human lung cancer remains to be determined. The purpose of this study is to determine clinicopathological and prognostic significance of cathepsin D expression in non-small cell lung cancer. Method : Using a polyclonal antibody, immunohistochemical analysis of cathepsin D was performed on paraffin embedded sections of tumors obtained surgically from 54 patients with non-small cell lung cancer (37 squamous cell carcinoma, 14 adenocarcinoma, 2 large cell carcinoma, and 1 undifferentiated carcinoma). Results : Eighteen patients (33.3%) showed positive immunoreactivities of cathepsin D in tumor cells. No significant correlation of cathepsin D expression in tumor cells was found in p-stage (surgical-pathologic stage), tumor size, tumor factor, nodal involvement, and differentiation. Of 54 patients, 29 (53.7%) patients showed moderate to massive cathepsin D-positive stromal cells within the tumor tissues, while the rest (46.3%) showed few cathepsin D-positive stromal cells within the tumor tissues. Cathepsin D expression in stromal cells was significantly associated with p-stage in non-small cell lung canær (p=0.031). No significant correlation of the degree of cathepsin D-positive stromal cells was found in tumor size, T -factor, nodal involvement, differentiation Cathepsin D expression status in tumor cells and stromal cells was not significantly associated with prognosis expressed by survival rate. The results of multivariate analyses of variables possibly associated with prognosis showed that nodal involvement was the only independent prognostic factor in all patients. Conclusion : Cathepsin D expression in stromal cells was significantly associated with p-stage in non-small cell lung cancer. However, it was not related to other clinicopathologic features and prognosis, and Cathepsin D expression in tumor was not related to p-stage and prognosis.

• Tuberculosis and Respiratory Diseases
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• v.55 no.5
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• pp.499-505
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• 2003

Background : The brain is a common site of a metastasis in lung cancer patients. If left untreated, the patients succumb to progressive neurological deterioration with a lower survival rate than with other metastases sites. Contrast-enhanced MR imaging in the absence of symptoms or clinical signs is not recommended for identifying a cerebral metastasis in lung cancer patients because of management effectiveness. This pilot study was performed to estimate whether or not limited brain MR imaging, which has a lower cost, could be used to replace conventional brain MR imaging. Method : Between April 1999 and March 2001, 43 patients with a primary lung cancer and the others (breast cancer, stomach cancer, colon cancer, malignant melanoma etc), who had neurological symptoms and signs, were examined using conventional brain MR imaging to examine brain metastases. The control group involved four patients who had no evidence of brain metastases the sensitivity, specificity and correlation of limited brain MR imaging were compared with conventional brain MR imaging. Results : All the 43 patients who were examined with conventional brain MR imaging showed evidence of brain metastases, whereas limited brain MR imaging indicated that 42 patients had brain metastases(sensitivity=97.67%). One patient in whom limited brain MR imaging showed no brain metastasis had a metastasis in the cerebellum, as shown by the contrast-enhanced T1 weighted axial view using conventional brain MR imaging. The conventional brain MR imaging and the limited brain MI imaging of the 4 control patients both indicated no brain metastases (specificity=100 %). The Pearson Correlation of the two groups was 0.884(Confidence Interval : 99%) observed. Conclusion : Limited brain MR imaging can detect a brain metastasis with the same accuracy. In addition, it is cost-effective (229,000 won, 180$) compared to conventional brain MR imaging(529,000 won, 480$) when patients had neurological symptoms and signs or staging.

• Journal of Life Science
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• v.29 no.4
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• pp.410-420
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• 2019

Citrus unshiu peel extracts possess a variety of beneficial effects, and studies on their anticancer activity have been reported. However, the exact mechanisms underlying this activity remain unclear. In the current study, the apoptotic effect of ethanol extract of C. unshiu peel (EECU) on human breast adenocarcinoma MDA-MB-231 cells and related mechanisms were investigated. The results showed that the survival rate of MDA-MB-231 cells treated with EECU was significantly inhibited in a concentration-dependent manner, which was associated with the induction of apoptosis. EECU-induced apoptosis was associated with the activation of caspase-8 and caspase-9, which initiate extrinsic and intrinsic apoptosis pathways, respectively, and caspase-3, a representative effect caspase. EECU suppressed the expression of the inhibitor of apoptosis family of proteins, leading to an increased Bax/Bcl-2 ratio and proteolytic degradation of poly (ADP-ribose) polymerase. EECU also enhanced the loss of the mitochondrial membrane potential and cytochrome c release from the mitochondria to the cytosol, along with truncation of Bid. In addition, EECU activated AMP-activated protein kinase (AMPK), and compound C, an AMPK inhibitor, significantly weakened EECU-induced apoptosis and cell viability reduction. Furthermore, EECU promoted the generation of reactive oxygen species (ROS), which acted as upstream signals for AMPK activation as pretreatment of cells, with the antioxidant N-acetyl cysteine reversing both EECU-induced AMPK activation and apoptosis. Collectively, these findings suggest that EECU inhibits MDA-MB-231 adenocarcinoma cell proliferation by activating intrinsic and extrinsic apoptotic pathways, which was mediated through ROS/AMPK-dependent pathways.

• The Journal of the Korean bone and joint tumor society
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• v.9 no.1
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• pp.1-11
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• 2003

Purpose: To analysis of the result of the treatment of metastatic diaphyseal fracture of the humerus with closed interlocking intrameduallry nailing. Materials and Methods: Among surgically treated 29 patients with pathologic or impending fracture of diaphysis of the humeurs, 13 patients (16 cases) treated with closed intramedullary interlocking nail were selected for the study. The final result of pain relief and functional recovery was evaluated by modified rating system of Perez et al. Results: Primary cancer was diagnosed after fracture was developed in 2 patients and pathologic or impending fracture was occurred average period of 28.9 months after primary cancer was diagnosed. The main primary malignancies were multiple myeloma, lung cancer and breast cancer. Mean survival after humeral metastasis was 11.7 months. The final result was superior to fair in 13 of 16 cases, and poor in 3 cases with progression of tumor spread or distant dissemination to the ipsilateral fingers. Except the latter 3 patients and other 3 patients, who died before 3 months postoperatively, bony union was achieved in 10 cases. There were no complications related to surgery. Conclusion: Closed interlocking intrameduallry nailing is accomplished with brief operative time, small amount of bleeding and provides immediate stability with resultant early return of function to the arm. Additionally it allows early postoperative irradiation. However, some of our cases shows that intramedullary nailing can accelerate tumor spread and metastases elsewhere, so that serious consideration must be given in planning this treatment. In conclusion, the functional status before fracture, life expectancy, type of tumor and extent of involvement should be carefully considered to decide operative treatment of metastatic disease.

• The Journal of the Korean bone and joint tumor society
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• v.6 no.1
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• pp.1-9
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• 2000

Purpose : Spine is one of the most common sites of the metastatic bone tumors. Conservative management such as chemotherapy or radiotherapy has been preferred in most cases. However, the neurologic deficit has not been usually improved, and the quality of life was poor. The purpose of this study was to show the efficacy of the surgical treatments for metastatic spinal tumors in terms of postoperative improvements of neurologic deficit and survival time. Materials and Methods : Authors have reviewed the literatures and analyzed 14 patients of metastatic spinal tumors who were received operative treatments between August 1991 and June 1999 at the our department of orthopaedic surgery. Results : The most frequent primary tumor was breast cancer in women and lung cancer in men. The thoracic region was the most common site. There was a preponderance of females over males, and the age ranged between 4th and 8th decade. The indications of surgical treatment comprised instability, progressive neurologic findings, resistance to radiotherapy, pathological fracture, long life expectancy( >6weeks), isolated metastasis and need for pathological diagnosis. The degree of preoperative neurological deficit might influence on the improvement of clinical symptoms after surgery. Conclusion : The surgical treatment reduced the neurological deficit and pain regardless of the operative methods. In the early stage of neurological deficit, the surgical treatment was important for better prognosis. Recently early active operative treatment was performed for metastatic spinal tumor to minimize the intractable pain and to prevent the progression of the neurologic deficit. Early intervention can improve the quality of life and long term survival.