• Radiation Oncology Journal
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• v.26 no.2
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• pp.91-95
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• 2008

Purpose: To evaluate the response and survival rate after three-dimensional conformal radiation therapy(3D-CRT) of patients with a solitary sternal relapse of breast cancer. Materials and Methods: Seventeen patients between May 1996 and June 2005 were evaluated with the salvage 3D-CRT treatment of a solitary sternal relapse of breast cancer. The treatment fields included the gross tumor volume with 2 cm margins. The total radiation dose was $35.0{\sim}61.5$ Gy(biologic effective dose of $43.7{\sim}76.9Gy_{10}$ using an $\alpha/\beta$ ratio of 10 Gy), with a daily dose of $1.8{\sim}3.0$ Gy. The tumor response was evaluated by the change in maximum tumor size via follow up CT scans $1{\sim}3$ months after the completion of treatment. Results: An objective tumor response was achieved in all patients, with a complete response in 5 patients and a partial response in 12 patients. The 5-year overall survival rate was 51.9%(median survival time: 27 months), and the most important factor affecting overall survival was the disease-free interval(interval from primary surgery of breast cancer to the development of sternal metastasis): The 5-year overall survival rate was 61.8% for patients with a disease-free interval ${\geq}12$ months and 0.0% for patients with disease-free interval <12 months(p=0.03). Conclusion: The response to 3D-CRT was good in patients with solitary sternal relapse of breast cancer. Particularly, patients with long disease-free interval from primary surgery survived significantly longer than patients with short disease-free interval from primary surgery.

• Nuclear Medicine and Molecular Imaging
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• v.43 no.4
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• pp.287-293
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• 2009

Purpose: This study is to evaluate rib fractures on bone scan in breast cancer patients treated with breast cancer surgery and radiation therapy and to evaluate its relation with radiation therapy and operation modality. Materials and Methods: Two hundred seventy cases that underwent serial bone scan after breast cancer surgery and radiation therapy were enrolled. Bone scan and chest a findings of rib fracture were analyzed. Results: The rib uptake was seen in 74 of 270 cases (27.4%) on bone scan and 50 cases (18.5%) were confirmed to have rib fracture by chest CT. The rate of modified radical mastectomy in patients with rib fracture was significantly higher than that in patients without rib fracture (66.0% vs. 27.0%, p = 0.000). The rate of additional radiation therapy to axillar or supraclavicular regions in patients with rib fracture was significantly higher than that in patients without rib fracture (62.0% vs. 28.6%, p =0.000). Rib fracture was seen most frequently at 1-2 years after radiation therapy (51.9%) and single rib fracture was seen most frequently (55.2%). Of total 106 rib fractures, focal rib uptake was seen in 94 ribs (88.7%) and diffuse rib uptake was seen in 12 ribs (11.3%). On one year follow-up bone scan, complete resolution of rib uptake was seen in 15 ribs (14.2%). On chest a, the rate of fracture line in ribs with intense uptake was significantly higher than that in ribs with mild or moderate uptake (p = 0.000). The rate of presence of fracture line in ribs with focal uptake was significantly higher than that in ribs with diffuse uptake (p = 0.001). Conclusion: Rib fracture in breast cancer patients after radiation therapy was related to radiation portal and operation modality. It should be interpreted carefully as a differential diagnosis of bone metastasis.

• Radiation Oncology Journal
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• v.22 no.1
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• pp.11-16
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• 2004

Purpose: To evaluate the survival rate, local failure rate and patterns of failure, and analyze the prognostic factors affecting local relapse of ductal carcinoma in situ treated with breast conserving surgery and radiotherapy Materials and Methods: From June 1995 to December 2001, 96 patients with ductal carcinoma in situ treated with breast conserving surgery and radiotherapy were retrospectively analyzed. The operations were either local or wide excision in all patients, with an axillary lymph node dissection performed in some patients. Radiation dose to the whole breast was 50.4 Gy, over 5 weeks, with 1.8 Gy daily fractions, with additional doses ($10\~14$ Gy) administered to the primary tumor bed in some patients with close ($\leq$2 mm) or positive resection margin. The median follow-up period was 43 months (range $10\~102$ months). Results: The 5-year local relapse free survival and overall survival rates were 91 and $100\%$ respectively. Local relapse occurred in 6 patients ($6.3\%$). Of the 6 recurrences, one was invasive ductal cell carcinoma. With the exception of one, all patients recurred 2 years after surgery. There was no regional recurrence or distant metastasis. Five patients with local recurrence were salvaged with total mastectomy, and are alive with no evidence of disease. One patient with recurrent invasive ductal cell carcinoma will receive salvage treatment. On analysis of the prognostic factors affecting local relapse, none of the factors among the age, status of resection margin, comedo type and nuclear grade affected local relapse. Operation extent also did not affect local control (p=0.30). In the patients with close resection margin, boost irradiation to the primary tumor bed did not affect local control (p=1.0). Conclusions: The survival rate and local control of the patients with ductal carcinoma in situ treated with breast conserving surgery and radiotherapy were excellent. Close resection margin and boost irradiation to the primary tumor bed did not affect local relapse, but further follow-up with much more patients is needed.

• Journal of Life Science
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• v.27 no.11
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• pp.1245-1255
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• 2017

Most cancer cells produce ATP predominantly through glycolysis instead of through mitochondrial oxidative phosphorylation, even in the presence of oxygen. The phenomenon is termed the Warburg effect, or the glycolytic switch, and it is thought to increase the availability of biosynthetic precursors for cell proliferation. EMTs have critical roles in the initiation of the invasion and metastasis of cancer cells. The glycolytic switch and EMT are important for tumor development and progression; however, their correlation with tumor progression is largely unknown. The Snail transcription factor is a major factor involved in EMT. The Snail expression is regulated by distal-less homeobox 2 (Dlx-2), a homeodomain transcription factor that is involved in embryonic and tumor development. The Dlx-2/Snail cascade is involved in Wnt-induced EMTs and the glycolytic switch. This study showed that in response to Wnt signaling, the Dlx-2/Snail cascade induces the expression of PFKFB2, which is a glycolytic enzyme that synthesizes and degrades fructose 2, 6-bisphosphate (F2,6BP). It also showed that PFKFB2 shRNA prevents Wnt-induced EMTs in the breast-tumor cell line MCF-7. The prevention indicated that glycolysis is linked to Wnt-induced EMT. Additionally, this study showed PFKFB2 shRNA suppresses in vivo tumor metastasis and growth. Finally, it showed the PFKFB2 expression is higher in breast, colon and ovarian cancer tissues than in matched normal tissues regardless of the cancers' stages. The results demonstrated that PFKFB2 is an important regulator of EMTs and metastases induced by the Wnt, Dlx-2 and Snail factors.

• The Korean Journal of Nuclear Medicine
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• v.37 no.6
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• pp.428-436
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• 2003

Purpose: Increased periarticular uptake could be associated with peripheral bone marrow expansion in cancer patients with axial bone marrow metastasis. We compared bone scan and bone marrow scan to investigate whether the increased whole body count in patients with increased periarticular uptake on bone scan is useful in the diagnosis of axial marrow metastasis, and evaluate the role of additional bone marrow scan in these cases. Materials and methods: Twelve patients with malignant diseases who showed increased periarticular uptake on bone scan were included. Whole body count was measured on bone scan and it is considered to be increased when the count is more than twice of other patients. Bone marrow scan was taken within 3-7 days. Results: Five hematologic malignancy, 3 stomach cancer, 2 breast cancer, 1 prostate cancer and 1 lung cacner were included. All three patients with increased whole body count on bone scan showed axial marrow suppression and peripheral marrow expansion. Eight of 9 patients without increased whole body count showed axial marrow suppression and peripheral marrow expansion. One turned out to be blastic crisis of chronic myelogeneous leukemia, and seven showed normal axial marrow with peripheral marrow expansion in chronic anemia of malignancy. The last one without increased whole body count showed normal bone marrow scan finding. Conclusion: Increased whole body count on bone scan could be a clue to axial bone marrow metastasis in cancer patients with increased periarticular uptake, and bone marrow scan is a valuable method for differential diagnosis in these cases.

• The Korean Journal of Nuclear Medicine Technology
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• v.14 no.2
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• pp.133-137
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• 2010

Purpose: Breast cancer is known to be more vulnerable to bone metastasis and lymph node metastasis than other types of cancer, and nuclear examinations whole body bone scan and lymphoscintigraphy are performed commonly before and after breast cancer operation. In case whole body bone scan is performed on the day before lymphoscintigraphy, the radiopharmaceutical taken into and remaining in the bones provides anatomical information for tracking and locating sentinel lymph nodes. Thus, this study purposed to examine how much bone density affects in locating sentinel lymph nodes. Materials and Methods: The subjects of this study were 22 patients (average age $52{\pm}7.2$) who had whole body bone scan and lymphoscintigraphy over two days in our hospital during the period from January to December, 2009. In the blind test, 22 patients (average age $57{\pm}6.5$) who had lymphoscintigraphy using $^{57}Co$ flood phantom were used as a control group. In quantitative analysis, the relative ratio of the background to sentinel lymph nodes was measured by drawing ROIs on sentinel lymph nodes and the background, and in gross examination, each of a nuclear physician and a radiological technologist with five years' or longer field experience examined images through blind test in a five-point scale. Results: In the results of quantitative analysis, the relative ratio of the background to sentinel lymph nodes was 14.2:1 maximum and 8.5:1 ($SD{\pm}3.48$) on the average on the front, and 14.7:1 maximum and 8.5:1 ($SD{\pm}3.42$) on the average on the side. In the results of gross examination, when $^{57}Co$ flood phantom images were compared with images containing bones, the score was relative high as 3.86 ($SD{\pm}0.35$) point for $^{57}Co$ flood phantom images and 4.09 ($SD{\pm}0.42$) for bone images. Conclusion: When whole body bone scan was performed on the day before lymphoscintigraphy, the ratio of the background to sentinel lymph nodes was over 10:1, so there was no problem in locating lymph nodes. In addition, we expect to reduce examination procedures and improve the quality of images by indicating the location of sentinel lymph nodes using bone images as body contour without the use of a source.

• Journal of radiological science and technology
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• v.36 no.4
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• pp.313-318
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• 2013

Positron emission tomography/computed tomography (PET/CT) imaging with fluorodeoxyglucose (FDG) have been used as a powerful fusion modality in nuclear medicine not only for detecting cancer but also for staging and therapy monitoring. Nevertheless, there are various causes of FDG uptake in normal and/or benign tissues. The purpose of present study was to investigate whether additional delayed imaging can improve the diagnosis to differentiate the rates of FDG uptake at axillary lymph nodes (ALN) between malignant and benign in breast cancer patients. 180 PET/CT images were obtained for 27 patients with ALN uptake. The patients who had radiotherapy and chemotherapy were excluded from the study. $^{18}F$-FDG PET/CT scan at 50 min (early phase) and 90 min (delayed phase) after $^{18}F$-FDG injection were included in this retrospective study. The staging of cancers was confirmed by final clinical according to radiologic follow-up and pathologic findings. The standardized uptake value (SUV) of ALN was measured at the Syngo Acquisition Workplace by Siemens. The 27 patients included 18 malignant and 9 ALN benign groups and the 18 malignant groups were classified into the 3 groups according to number of metastatic ALN in each patient. ALNs were categorized less than or equal 3 as N1, between 4 to 9 as N2 and more than 10 as N3 group. Results are expressed as the mean${\pm}$standard deviation (S.D.) and statistically analyzed by SPSS. As a result, Retention index (RI-SUV max) in metastasis was significantly higher than that in non-metastasis about 5 fold increased. On the other hand, RI-SUV max in N group tended to decrease gradually from N1 to N3. However, we could not prove significance statistically in malignant group with ANOVA. As a consequence, RI-SUV max was good indicator for differentiating ALN positive group from node negative group in breast cancer patients. These results show that dual-time-point scan appears to be useful in distinguishing malignant from benign.

• Journal of Life Science
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• v.26 no.4
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• pp.439-445
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• 2016

Soybean leaves, a Korean edible plant material, have been reported to prevent the development of osteoporosis and breast cancer. Based on this rational, soybean fallen leaves ethanolic extract (SBFL) was used for the experiment of cell invasion related to metastasis and antioxidant activity. The effect of SBFL on matrix metalloproteinases (MMPs) in human fibrosarcoma cells, HT1080 as well as its anti-oxidant activity was investigated in this study. The effect of SBFL on scavenging activity of reactive oxygen species was evaluated in vitro using lipid peroxidation assay,DPPH radical and reducing power assay. SBFL showed the positive effects on antioxidant activity, compared with vitamin C and vitamin E used as positive controls. Furthermore, SBFL showed cytotoxicity above 16 µg/ml in MTT assay. In particular, it was found that SBFL decreased the activation of MMP-9 stimulated by phorbol 12-myristate 13-acetae (PMA) and phenazine methosulfate (PMS). SBFL treatment increased the expression levels of p-FoxO-1 and SOD-1. Moreover, SBFL inhibited cell invasion stimulated by vascular endothelial growth Factor (VEGF). These results indicate that SBFL could inhibit cell invasion related to the activation of MMP-9 and oxidative stress, suggesting that it could be available as a main ingredient for prevention of metastasis.

• 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 Korean Neurosurgical Society
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• v.61 no.5
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• pp.633-639
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• 2018

Objective : We investigated the outcomes of repeat stereotactic radiosurgery (SRS) for metastatic brain tumors that locally recurred despite previous SRS, focusing on the tumor control. Methods : A total of 114 patients with 176 locally recurring metastatic brain tumors underwent repeat SRS after previous SRS. The mean age was 59.4 years (range, 33 to 85), and there were 68 male and 46 female patients. The primary cancer types were non-small cell lung cancer (n=67), small cell lung cancer (n=12), gastrointestinal tract cancer (n=15), breast cancer (n=10), and others (n=10). The number of patients with a single recurring metastasis was 95 (79.8%), and another 19 had multiple recurrences. At the time of the repeat SRS, the mean volume of the locally recurring tumors was 5.94 mL (range, 0.42 to 29.94). We prescribed a mean margin dose of 17.04 Gy (range, 12 to 24) to the isodose line at the tumor border primarily using a 50% isodose line. Results : After the repeat SRS, we obtained clinical and magnetic resonance imaging follow-up data for 84 patients (73.7%) with a total of 108 tumors. The tumor control rate was 53.5% (58 of the 108), and the median and mean progression-free survival (PFS) periods were 246 and 383 days, respectively. The prognostic factors that were significantly related to better tumor control were prescription radiation dose of 16 Gy (p=0.000) and tumor volume less than both 4 mL (p=0.001) and 10 mL at the repeat SRS (p=0.008). The overall survival (OS) periods for all 114 patients after repeat SRS varied from 1 to 56 months, and median and mean OS periods were 229 and 404 days after the repeat SRS, respectively. The main cause of death was systemic problems including pulmonary dysfunction (n=58, 51%), and the identified direct or suspected brain-related death rate was around 20%. Conclusion : The tumor control following repeat SRS for locally recurring metastatic brain tumors after a previous SRS is relatively lower than that for primary SRS. However, both low tumor volume and high prescription radiation dose were significantly related to the tumor control following repeat SRS for these tumors after previous SRS, which is a general understanding of primary SRS for metastatic brain tumors.