• Nuclear Medicine and Molecular Imaging
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• v.40 no.1
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• pp.9-15
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• 2006

Purpose: Previous studies have not showed consistent results for the level of expression of sodium/iodide symporter (NIS) in thyroid diseases, especially malignant tumor. We undertook this study to evaluate the distribution of NIS expression in malignant thyroid diseases and compare with that in benign thyroid disease. Materials and Methods: Total patients were 119 cases (Men 15, $48{\pm}13$ yrs). Total number of samples were 205 pieces. In malignant thyroid disease, there were 153 samples: 90 in papillary carcinoma, 4 in follicular carcinoma, 2 in medullary carcinoma and 57 in metastatic lymph node. In benign thyroid disease, there were 52 samples: 36 in goiter/cyst, 11 in thyroiditis and 5 in follicular adenoma. Using immunohistochemical methods, we probed 205 samples with monoclonal anti-NIS Ab. Grading of staining was stored as 0 (negative or absent), 1 (weakly positive), 2 (moderately positive) or 3 (strongly positive). Expression rate (ER) of NIS positivity in individual disease entity was expressed as percentage of total number divided by number in 2 plus 3 grade. Results: ERs of malignant thyroid diseases were 63% in papillary carcinoma, 81% in metastatic lymph node, 71% in follicular carcinoma and 100% in medullary carcinoma. ERs of benign thyroid disease were 53% in goiter/cyst, 64% in thyroiditis and 40% in follicular adenoma. ER of malignant thyroid diseases was higher than benign thyroid diseases (71% vs 54%). Grading of NIS expression in papillary carcinoma or goiter/cyst was heterogeneously distributed in considerable cases. Normal tissue also showed heterogeneous distribution of NIS expression, which was not correlated with that of primary lesion. Conclusion: In papillary thyroid carcinoma, distribution of NIS expression was heterogeneous and increased, and not different compared with that of benign thyroid disease.

• Radiation Oncology Journal
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• v.12 no.2
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• pp.165-173
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• 1994

Purpose : Metastatic cancer to the brain is a major problem for the patients with bronchogenic carcinoma, and most of these patients have a limited survival expectancy. To increase tumor control and / or to decrease late morbidity with possible shortening in over-all treatment period, multiple daily fraction technique for brain metastasis was performed. The author reperesented the results of accelerated fractionation radiotherapy in patients with brain metastases from non-small cell lung cancer. Materals and Methods : Twenty-six patients with brain metastases from non-small cell lung cancer between 1991 and 1993 received brain radiotherapy with a total dose of 48 Gy, at 2 Gy per fraction, twice a day with a interfractional period of 6 hours, and delivered 5 days a week. The whole brain was treated to 40 Gy and boost dose escalated to 8 Gy for single metastatic lesion by reduced field. Twenty-four of the 26 patients completed the radiotherapy. Radiotherapy was interupted in two patients suggesting progressive intracerebral diseases. Results : This radiotherapy regimen appears to be comparable to the conventional scheme in relief from symptoms. Three of the 24 patients experienced nausea and or vomiting during the course of treatment because of acute irradiation toxicity. The author observed no excessive toxicity with escalating dose of irradiation. An increment in median survival, although not statistically significant(p>0.05), was noted with escalating doses(48 Gy) of accelerated fractionation(7 months) compared to conventional treatment(4.5 months). Median survival also increased in patients with brain solitary metastasis(9 months) compared to multiple extrathoracic sites(4 months), and in patients with good performance status(9 months versus 3.5 months), they were statistically significant (p<0.01). Conclusion : The increment in survival in patients with good prognostic factors such as controlled primary lesion, metastasis in brain only and good perfomance status appeared encouraging. Based on these results, a multi-institutional prospective randomized trial should be initiated to compare the twice-a-day and once-a-day radiotherapy schemes on patients with brain metastasis with careful consideration for the patients' quality of life.

• Nuclear Medicine and Molecular Imaging
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• v.40 no.6
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• pp.309-315
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• 2006

Purpose: Accurate evaluation of cervical lymph node (LN) metastasis of head and neck squamous cell canter (SCC) is important to treatment planning. We evaluated the diagnostic accuracy of F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for the detection of cervical LN metastasis of head and neck SCC and performed a retrospective comparison with CT/MRI findings. Materials & Methods: Seventeen patients with pathologically proven head and neck SCC underwent F-18 FDG PET/CT and CT/MRI within 4 week before surgery. We recorded lymph node metastases according to the neck level system of imaging-based nodal classification. F-18 FDG PET/CT images were analyzed visually for assessment of regional tracer uptake in LN. We analyzed the differences in sensitivity and specificity between F-18 FDG PET/CT and CT/MRI using the Chi-square test. Results: Among the 17 patients, a total of 123 LN levels were dissected, 29 of which showed metastatic involvement. The sensitivity and specificity of F-18 FDG PET/CT for detecting cervical LN metastasis on a level-by-level basis were 69% (20/29) and 99% (93/94). The sensitivity and specificity of CT/MRI were 62% (18/29) and 96% (90/94). There was no significant difference in diagnostic accuracy between F-18 FDG PET/CT and CT/MRI. Interestingly, F-18 FDG PET/CT detected double primary tumor (hepatocellular carcinoma) and rib metastasis, respectively. Conclusion: There was not statistically significant difference of diagnostic accuracy between F-18 FDG PET/CT and CT/MRI for the detection of cervical LN metastasis of head and neck SCC. The low sensitivity of F-18 FDG PET/CT was due to limited resolution for small metastatic deposits.

• IMMUNE NETWORK
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• v.1 no.1
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• pp.36-44
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• 2001

Background : Peritoneal metastasis is one of the maj or types of the stomach cancer recurrence and the role of the adhesion molecules is thought to be very much important in this event. Retinoic acid (RA) has been known to induce the growth inhibition and differentiation of various malignancies, and apoptpsis and the change of expression of adhesion molecules have been reported to be involved in the action of RA. Methods : We studied the adhesion abilities of SNU-1, SNU-5, and SNU-6 cells to the peritoneal endothelial cells as well as the expression of the adhesion molecules (CD44, ICAM-1) in Western blot analysis. And also we studied the expression of apoptosis and the change of expression patterns of the various isoforms of CD44 and the change of the adhsion abilities of the cell line cells after RA treatment. Results: CD44 was expressed in SNU-5 and -16, together with an isoform in SNU-16. ICAM-1 was not expressed in any of the cell line cells tested. After the treatment of RA in the concentration range of $1-5{\times}10^{-5}M$ to three stomach cancer cell lines, growth inhibition, apoptosis and the change of expression of the CD44 were noted. After RA treatment, the expression of CD44H was weakly increased in SNU-1, and was markedly increased in SNU-5. In SNU-16, the expression of CD44H was decreased while that of CD44E were markedly increased. The adhesibility of cells to peritoneal cells was increased in relation with the increase of the CD44H expression, which shows the fact that the adhesibility of tumor cells to peritoneal mesothelial cells is mediated by CD44H recognizing hyaluronic acid. Conclusion : RA induces growth inhibition of stomach cancer cell line cells and increase the adhesiblity of stomach cancer cell line cells to peritoneal mesothelium. It is believed that RA decreases the metastatic ability of stomach cancer cells by upregulating the CD44H expression.

• IMMUNE NETWORK
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• v.2 no.3
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• pp.175-181
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• 2002

Background: S100A6 is a calcium-binding protein overexpressed in several tumor cell lines including melanoma with high metastatic activity and involved in various cellular processes such as cell division and differentiation. To detect S100A6 protein in patient' samples (ex, blood or tissue), it is essential to produce a monoclonal antibody specific to the protein. Methods: First, cDNA coding for ORF region of human S100A6 gene was amplified and cloned into the expression vector for GST fusion protein. We have produced recombinant S100A6 protein and subsequently, monoclonal antibodies to the protein. The specificity of anti-S100A6 monoclonal antibody was confirmed using recombinant S100A recombinant proteins of other S100A family (GST-S100A1, GST-S100A2 and GST-S100A4) and the cell lysates of several human cell lines. Also, to identify the specific recognition site of the monoclonal antibody, we have performed the immunoblot analysis with serially deleted S100A6 recombinant proteins. Results: GST-S100A6 recombinant protein was induced and purified. And then S100A6 protein excluding GST protein was obtained and monoclonal antibody to the protein was produced. Monoclonal antibody (K02C12-1; patent number, 330311) has no cross-reaction to several other S100 family proteins. It appears that anti-S100A6 monoclonal antibody reacts with the region containing the amino acid sequence from 46 to 61 of S100A6 protein. Conclusion: These data suggest that anti-S100A6 monoclonal antibody produced can be very useful in development of diagnostic system for S100A6 protein.

• Radiation Oncology Journal
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• v.34 no.4
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• pp.265-272
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• 2016

Purpose: The purpose of this study is to evaluate the treatment outcomes of adjuvant radiotherapy using vaginal brachytherapy (VB) with a lower dose per fraction and/or external beam radiotherapy (EBRT) following surgery for patients with stage I endometrial carcinoma. Materials and Methods: The subjects were 43 patients with the International Federation of Gynecology and Obstetrics (FIGO) stage I endometrial cancer who underwent adjuvant radiotherapy following surgery between March 2000 and April 2014. Of these, 25 received postoperative VB alone, while 18 received postoperative EBRT to the whole pelvis; 3 of these were treated with EBRT plus VB. The median EBRT dose was 50.0 Gy (45.0-50.4 Gy) and the VB dose was 24 Gy in 6 fractions. Tumor dose was prescribed at a depth of 5 mm from the cylinder surface and delivered twice per week. Results: The median follow-up period for all patients was 57 months (range, 9 to 188 months). Five-year disease-free survival (DFS) and overall survival (OS) for all patients were 92.5% and 95.3%, respectively. Adjuvant radiotherapy was performed according to risk factors and stage IB, grade 3 and lymphovascular invasion were observed more frequently in the EBRT group. Five-year DFS for EBRT and VB alone were 88.1% and 96.0%, respectively (p = 0.42), and 5-year OS for EBRT and VB alone were 94.4% and 96%, respectively (p = 0.38). There was no locoregional recurrence in any patient. Two patients who received EBRT and 1 patient who received VB alone developed distant metastatic disease. Two patients who received EBRT had severe complications, one each of grade 3 gastrointestinal complication and pelvic bone insufficiency fracture. Conclusion: Adjuvant radiotherapy achieved high DFS and OS with acceptable toxicity in stage I endometrial cancer. VB (with a lower dose per fraction) may be a viable option for selected patients with early-stage endometrial cancer following surgery.

• The Korean Journal of Food And Nutrition
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• v.25 no.4
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• pp.941-950
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• 2012

In order to develop new physiologically active polysaccharides from persimmon leaves, two different crude polysaccharides were prepared using hot water (PLW-0) and pectinase digestion (PLE-0) and their immuno-stimulating activities were estimated. PLW-0 and PLE-0 showed similar sugar compositions with 15 different sugars, including rarely observed sugars in general polysaccharides such as 2-O-methyl-fucose, 2-O-methyl-xylose, apiose, aceric acid, 3-deoxy-D-manno-2-octulosonic acid, and 3-deoxy-D-lyxo-2-heptulosaric acid, but the uronic acid content of PLE-0 was lower than that of PLW-0 caused by pectinase treatment. Both PLW-0 and PLE-0 showed potent anti-complementary activity in a dose-dependent manner which was similar to a known immuno-stimulating polysaccharide, PSK, from Coriolus versicolor. The activity of PLE-0 at a low concentration ($100{\mu}g/m{\ell}$) was higher than that of PLW-0. In an in vitro cytotoxicity analysis, PLW-0 and PLE-0 (up to $1,000{\mu}g/m{\ell}$) did not affect the growth of peritoneal macrophages and Colon 26-M3.1 carcinoma cells. In contrast, they enhanced lymphocyte proliferation activity. Peritoneal macrophages stimulated with PLW-0 and PLE-0 produced various cytokines, such as IL-6 and IL-12. However, PLE-0 was more effective on the cytokine production. Intravenous administration of PLW-0 and PLE-0 significantly augmented natural killer (NK) cell cytotoxicity against Yac-1 tumor cells 3 days after the treatment of polysaccharide fractions. But NK cells obtained from the PLE-treated group showed higher tumoricidal activity even at a low dose of $40{\mu}g$/mouse. In experimental lung metastasis of Colon 26-M3.1 carcinoma cells, prophylactic administration of PLW-0 and PLE-0 significantly inhibited lung metastasis in a dose-dependent manner and PLE-0 was more effective on the inhibition of cancer metasasis. The results lead us to conclude that the pectinase-treated process is indispensable to preparing polysaccharides with higher immune-stimulating activity from persimmon leaves.

• Journal of Chest Surgery
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• v.12 no.4
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• pp.324-335
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• 1979

During the period of 4 years from August 1975 to August 1979 one hundred and forty seven cases of lung cancer were seen at Paik Foundation Hospital in Seoul, Korea. Among these 147 cases, 104 patients had primary carcinoma of the lung and the remainder was metastatic carcinoma to the lung. Among these 104 primary carcinoma patients, 73 cases were proven histologically as primary carcinoma of the lung. There were three cases of alveolar cell carcinoma [Table 1 ]. This clinical observation is based on those 73 cases including three case reports of the alveolar cell carcinoma. 1. Peak incidence was observed in the 5th decade of life. Male to female ratio was 2 to 1 [Fig. 1]. 2. Pathological classifications were as follows: epidermoid carcinoma, 24 cases [32.9%]; undifferentiated carcinoma, 20 cases [27.4%]; adenocarcinoma, 15 cases [20.5%]; bronchioloalveolar carcinoma [5.5%] and positive cytology, 10 cases [13.7%] [Fig. 2]. 3. Evidence of inoperability was observed in 55 patients [75% of the 73 cases] [Table 3]. 4. Among those 73 cases, operability was evaluated in 18 patients or 25%. One patient refused operation and 17 patients [23.6%] were explored. In 11 [15%] out of 17 patients, thoracotomies were performed. Six cases were pneumonectomies and 5 cases were lobectomies or bilobectomies [Fig. 3]. 5. First case of alveolar cell carcinoma was a 46 year-old housewife complaining of cough and hemoptysis for one year. The plain chest X-ray and bronchogram showed characteristic pictures as Figures 4 and 5. A pneumonectomy was carried out. Histologically, a beautiful alveolar carcinoma consisted of the characteristic tall columnar epithelial cells, which were lining the alveolar spaces as seen in Figures 6, 7, 8, and 20. 6. In the second case of 41 year old male, predominant clinical feature was single, well defined mass in the right lower lobe [Fig. 10 and 11] on chest X-ray. Bilobectomized specimen showed fragile, soft and hard tissue containing mucoid secretions and focal yellowish necrosis with pigmentation on cut surface [Fig. 12]. Slides showed tumor cells lined up along the alveolar septa with papillary projections [Fig. 13 and 14]. 7. Third case of alveolar cell carcinoma was a 50-year-old housewife with hemoptysis. An outstanding clinical picture was a round to lobulated mass in the right upper lobe [Fig. 16]. She is living now, 2 years and 1 month post-operatively, but has arrived at terminal stage with military nodular disseminations to the contralateral lung [Fig. 19].

• Korean Journal of Head & Neck Oncology
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• v.17 no.2
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• pp.185-189
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• 2001

Background: Cervical metastasis of unknown origin is defined as histologic evidence of malignancy in the cervical lymph nodes with no apparent primary site of origin for the metastatic tumor. Patients and Methods: A retrospective review of 20 cervical metastasis of unknown origin diagnosed and managed between january 1989 and December 1999 at the Korea University was undertaken to determine outcome. Patient age ranged 46 to 78 years (mean 60). There were 17 men and 3 women. The aim of this study is to ananlyze the diagnostic approach and the result of treatment of the cervical metastasis of unknown origin. Result: Histopathologically, squamous cell carcinoma (15 case, 75%) were the most common, followed by adenocarcinoma (4 case, 20%), undifferentiated carcinoma (1 case, 5%) According to the criteria of the AJCC on staging, N1 was 2 cases, N2a 2 cases, N2b 5 cases, N2c 1 cases, N3 10 cases. Overall survival rate for all patients at 2 years was 45% and 5 years 25%, and in the combination therapy(surgery and radiotherapy group (12 cases)) it was 67% and 34% respectively, high compared with other treatment modality such as surgery or radiotherapy alone. In extracapsular spread positive group, 5 year survival rate was 12%, but was 33% in the extracapsular spread negative group. Conclusion: With no stastatical significance, extracapsular spread group was poor outcome in our study. Combination of radiotherapy and surgery was more effective treatment result than surgery alone or radiotherapy alone in our study. But, overall prognosis of cervical metastasis of unknown origin was very poor despite aggressive treatment (5 year survival rate: 25%).

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.22
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• pp.9823-9829
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• 2014

Background: High-dose methotrexate (HD-MTX) is recognized as an efficient component of therapy against pediatric osteosarcoma in combination with other drugs such as cisplatin (CDP), carboplatin (CBDCA), doxorubicin (ADM), etoposide (VP-16) and ifosfamide (IFO). Objectives: To demonstrate the feasibility and effectiveness of the HD-MTX/CDP/DOX/VP-16/IFO [MTX(+)] protocol comparable to CDP/ADM/CBDCA/IFO [MTX(-)] for treating childhood osteosarcoma at Ramathibodi Hospital (1999-2014). Materials and Methods: A retrospective analysis was conducted of osteosarcoma patients aged less than 18 years treated with two chemotherapeutic regimens between 1999 and 2014. A total of 45 patients received the MTX(-) and 21 the MTX(+) protocol. Results: Overall limb-salvage and amputation rate were 12.9% and 77.7%, respectively. Kaplan-Meier analysis results for 3-year disease free survival (DFS) and overall survival (OS) regardless of treatment regimens were $43.4{\pm}6.0%$ and $53.2{\pm}6.1%$ respectively. The 3-year DFS and OS were improved significantly with the MTX(+) protocol compared to MTX(-) protocol (p=0.010 and p=0.009, log rank test) [$69.8{\pm}10.5%$, $79.8{\pm}9.1%$ for MTX(+) and $31.1{\pm}6.9%$, $42.2{\pm}7.4%$ for MTX(-) protocol, respectively]. Patients with metastatic osteosarcoma treated with the MTX(+) protocol had statistically significant higher 3-year DFS and OS than those treated with the MTX(-) protocol ($66.7{\pm}13.6%$ and $15.0{\pm}8.0%$ for 3-year DFS, p=0.010, $73.3{\pm}13.2%$ and $20{\pm}8.9%$ for 3-year OS, p=0.006, respectively). The independent risk factors for having inferior 3-year DFS and OS were poor histological response (tumor necrosis <90%) and treatment with the MTX(-) protocol. The multivariate analysis identified only the treatment with the MTX(-) protocol as an independent predictor of inferior OS with a hazard ratio (HR) of 3.53 (95% confidence interval of 1.2-10.41, p=0.022). Conclusions: Our study demonstrated the tolerability, feasibility and efficacy of the HDMTX-based regimen improving the survival rate in pediatric osteosarcoma cases, in line with reports from developed countries.