• Journal of Chest Surgery
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• v.39 no.11 s.268
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• pp.828-837
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• 2006

Background: Tissue hypoxia is characteristic of many human malignant neoplasm, and hypoxia inducible factor-1(HIF-1) plays a pivotal role in essential adaptive response to hypoxia, and activates a signal pathway for the expression of the hypoxia-regulated genes, resulting in increasing $O_2$ delivery or facilitating metabolic adaptation to hypoxia. Increased level of HIF-$1{\alpha}$ has been reported in many human malignancies, but in non-small cell lung carcinoma the influence of HIF-$1{\alpha}$ on tumor biology, including neovascularization, is not still defined. In present study the relationship of HIF-$1{\alpha}$ expression on angiogenetic factors, relationship between the tumor proliferation and HIF-$1{\alpha}$ expression, interaction of HIF-$1{\alpha}$ expression and p53, and relationship between HIF-$1{\alpha}$ expression and clinico-pathological prognostic parameters were investigated. Material and Method: Archival tissue blocks recruited in this study were retrieved from fifty-nine patients with primary non-small cell lung carcinoma, who underwent pneumonectomy or lobectomy from 1997 to 1999. HIF-$1{\alpha}$, VEGF(vascular endothelial growth factor), and p53 protein expression and Ki-67 labeling index in tumor tissues were evaluated, using a standard avidin-biotin-peroxidase complex(ABC) immunohistochemistry. Relationship between the HIF-$1{\alpha}$ expression and VEGF, p53 overexpression and correlation between the HIF-$1{\alpha}$ expresseion and Ki-67 index were analyzed. Clinico-pathologic prognostic parameters were also analyzed. Result: HIF-$1{\alpha}$ expression in cancer cells was found in 24 of 59 cases of non-small cell lung carcinoma(40.7%). High HIF-$1{\alpha}$ expression was significantly associated with several pathological parameters, such as pathological TMN stage(p=0.004), pT stage(p=0.020), pN stage (p=0.029), and lymphovascular invasion(p=0.019). High HIF-$1{\alpha}$ expression was also significantly associated with VEGF immunoreactivity(p<0.001), and aberrant p53 expression(p=0.040). but was marginally associated with Ki-67 labeling index(p=0.092). The overall 5-year survival rate was 42.3%. The survival curve of patients with a high HIF-$1{\alpha}$ expression was worse than that of patients with low-expression(p=0.002). High HIF-$1{\alpha}$ expression was independent unfavorable factors with a marginal significance in multivariate analysis performed by Cox regression. Conclusion: It is suggested that high HIF-$1{\alpha}$ expression may be associated with intratumoral neovascularization possibly through HIF-VEGF pathway, and high HIF-$1{\alpha}$ expression could be associated with lymph node metastasis and post operative poor prognosis in patients with non-small cell lung carcinoma.

• The Korean Journal of Nuclear Medicine
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• v.29 no.4
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• pp.484-491
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• 1995

It is well known that hepatobiliary agent are taken up by metastatic hepatocellular carcinoma(HCC) as well as primary HCC. But the reported cases of the extrahepatic metastasis of HCC diagnosed by hepatobiliary scintigraphy are for the most part hematogenous ones. The relation of the uptake pattern of hepatobiliary agent in the primary and metastatic HCC is also still remains unknown. So we undertook this study to evaluate the relation of the hepatobiliary scintigraphic patterns of primary and metastatic HCC with different metastatic routes. Nine patients with primary HCC and twelve cases of metastatic HCC including four lung metastases, one bone metastasis, one right atrial metastasis, one peritoneal wall metastasis, and five lymph node metastases were studied with $^{99m}Tc-DISIDA$ scintigraphy. The images were taken on 10, 30 minutes, 1, 2, 4-6 hours. The overall detection rates of hematogenous metastases(lung and bone) is 60%(3 of 5), direct metastasis(right atrium and peritoneal wall), 100%(2 of 2) and lymphatic metastases, 0%(0 of 5). In four of five metastatic cases demonstrated with hepatobiliary scintigraphy, biliary agent is also taken up by primary HCC lesions. And the appearing time of the radioactivity in the direct metastatic HCC lesioin is same as that of primary HCC and in the cases of hematogenous metastasis, earlier than that of primary HCC. Hepatobiliary scintigraphy is more useful in the diagnosis of the metastatic HCC than primary HCC, in the cases of hematogenous and direct metastasis.

• Nuclear Medicine and Molecular Imaging
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• v.43 no.5
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• pp.429-435
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• 2009

Purpose: The purpose of this study was to assess the prognostic value of preoperative FDG-PET in colorectal cancer (CRC) patients with hepatic metastasis (HM). Materials and Methods: 24 CRC patients (M:F=14:10; age, $63{\pm}10$ yrs) with HM who had undergone preoperative FDG PET were included. Cure-intent surgery was performed in all the patients and HMs were controlled using resection (n=13), radio-frequency ablation (RFA) (n=7), and resection plus RFA (n=4). Potential prognostic markers tested were maxSUV of primary tumor, maxSUV of HM, maxSUV ratio of HM over primary tumor (M/P ratio), histologic grade, CEA level, venous/lymphatic/nerve invasion, T stage, N stage, no. of HM, no. of lymph node metastasis, and treatment modality of HM. Results: 14 CRC patients developed a recurrence with a median follow-up duration of 244 days, whereas 10 patients did not develop recurrence with a median follow-up duration of 504 days. M/P ratios but other potential prognostic markers were significantly higher in the recurrent patients ($0.72{\pm}0.14$) than recurrence-free patients ($0.54{\pm}0.23$) (p=0.038). M/P ratio only was found to predict recurrence by Cox multivariate analysis (hazard ratio 37.7, 95% confidence interval 2.01-706.1, p=0.016). The 11 patients with lower M/P ratio of <0.61 had significantly better disease-free survival rate than the 13 patients with higher M/P ratio (${\geq}0.61$) (p=0.026). Conclusion: maxSUV ratio of HM over primary tumor (M/P ratio) may be useful for prognosis prediction of CRC patients with HM. Higher FDG uptake of HM than that of primary tumor may indicate a more advanced status in stage IV CRC.

• Journal of Chest Surgery
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• v.41 no.1
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• pp.74-81
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• 2008

Background: Fascin is an actin-bundling protein that induces membrane protrusions and it increases cell motility in various transformed cells. Esophageal cancer is one of the most lethal malignancies, and it exhibits extensive local invasion or frequent regional lymph node metastasis even after curative surgery. We investigate the expression of fascin by performing immunohistochemistry to evaluate the clinical characteristics and prognostic significance of its expression in esophageal cancer patients. Material and Method: Immunochemistry for fascin was performed on 76 tumor samples from 76 patients who underwent esophageal cancer operations. The expression levels of fascin in the 76 esophageal cancer tissues were compared with those in the corresponding normal esophageal epithelium. The fascin-positive samples were defined as those showing more than 75% of fascin-positive cells. Result: Overall, a fascin positive expression was detected in 39 (51.3%) out of the total 76 cases. The tumors with positive fascin expression tended to more frequently show a higher stage (p=0.030), and a higher T-factor (p=0.031). The prognosis of the fascin negative group was significantly better than that of the fascin positive group (p=0.004). Multivariate analysis revealed that lymphovascular invasion and the fascin expression were independent prognostic factors. Conclusion: Fascin was expressed in 513% of the esophageal cancer tissues and a positive expression of fascin was associated with more advanced tumor progression and recurrence. Our study suggests that the fascin expression may be an independent prognostic factor for an unfavorable clinical course few those patients suffering with esophageal cancer.

• Radiation Oncology Journal
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• v.24 no.3
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• pp.157-163
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• 2006

[ $\underline{Purpose}$ ]: To evaluate the role of postoperative adjuvant chemoradiotherapy in rectal cancer, we retrospectively analyzed the treatment outcome of patients with rectal cancer taken curative surgical resection and postoperative adjuvant chemoradiotherapy. $\underline{Materials\;and\;Methods}$: A total 46 patients with AJCC stage II and III carcinoma of rectum were treated with curative surgical resection and postoperative adjuvant chemoradiotherapy. T3 and T4 stage were 38 and 8 patients, respectively. N0, N1, and N2 stage were 12, 16, 18 patients, respectively. Forty patients received bolus infusions of 5-fluorouracil ($500\;mg/m^2/day$) with leucovorin ($20\;mg/m^2/day$), every 4 weeks interval for 6 cycles. Oral Uracil/Tegafur on a daily basis for $6{\sim}12$ months was given in 6 patients. Radiotherapy with 45 Gy was delivered to the surgical bed and regional pelvic lymph node area, followed by $5.4{\sim}9\;Gy$ boost to the surgical bed. The follow up period ranged from 8 to 75 months with a median 35 months. $\underline{Results}$: Treatment failure occurred in 17 patients (37%). Locoregional failure occurred in 4 patients (8.7%) and distant failure in 16 patients (34.8%). There was no local failure only. Five year actuarial overall survival (OS) was 51.5% and relapse free survival (RFS) was 58.7%. The OS and RFS were 100%, 100% in stage N0 patients, 53.7%, 47.6% in N1 patients, and 0%, 41.2% in N2 patients (p=0.012, p=0.009). The RFS was 55%, 78.5%, and 31.2% in upper, middle, and lower rectal cancer patients, respectively (p=0.006). Multivariate analysis showed that N stage (p=0.012) was significant prognostic factor for OS and that N stage (p=0.001) and location of tumor (p=0.006) were for RFS. Bowel complications requiring surgery occurred in 3 patients. $\underline{Conclusion}$: Postoperative adjuvant chemoradiotherapy was an effective modality for locoregional control of rectal cancer. But further investigations for reducing the distant failure rate are necessary because distant failure rate is still high.

• 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.26 no.9
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• pp.1056-1062
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• 2016

Lung cancer is currently the most common malignant disease and the leading cause of mortality in the world and non-small cell lung cancer (NSCLC) accounts for 75-80% of lung cancer cases. miR-155 gene was found to be over expressed in several solid tumors, such as thyroid carcinoma, breast cancer, colon cancer, cervical cancer, pancreatic ductal adenocarcinoma (PDAC) and lung cancer. The aims of this study were to define the expression of miR-155 in lung cancer and its associated clinic-pathologic characteristics. Total RNA was purified from formalin-fixed, paraffin-embedded NSCLC tissues and benign lung tissues. Expression of miR-155 in human lung cancer tissues were evaluated as mean fold changes of miR-155 in cancer tissues compared to benign lung tissues by quantitative real-time reverse transcriptase polymerase chain reaction (real-time qRT-PCR) and associations of miR-155 expression with clinic-pathologic findings of cancer. Compared with the benign control group, miR-155 expression was significantly overexpressed in NSCLCs (p=<0.001). miR-155 was more overexpressed in squamous cell carcinoma than in adenocarcinoma. Poorly differentiated tumors showed significantly overexpression of miR-155 than well-differentiated tumors (p=<0.001). Overexpression of miR-155 was significantly associated with lymph node metastasis (p=<0.05). In survival analysis for all NSCLC patients, high miR-155 expression was significantly correlated with worse overall survival (p=<0.05). These results suggested that miR-155 might play an important role in lung cancer progression and metastasis.

• Radiation Oncology Journal
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• v.12 no.3
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• pp.377-386
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• 1994

Purpose: The role of radiotherapy in the management of patients with locoregional recurrent cervix cancer after radical surgery were retrospectively analyzed. Methods and materials: Twenty-eight patients treated with radiotherapy for locoregional recurrence after primary surgery for carcinoma of the cervix between 1989 and 1993 were analyzed. The median follow-up of survivors was 15 months (ranged 7-43 months). Eight patients had their disease confined to the vagina and 19 patients($68\%$) had pelvic mass as part of their locoregional recurrent disease. Within 24 months after the initial surgery, $82\%$ of recurrences manifested themselves. All patients had whole pelvic irradiation with or without intracavitary radiotherapy(ICR). Results: Complete response(CR) was achieved in 18 patients($54\%$). Five of eighteen patients($28\%$) with initial CR developed second locoregional recurrence. Response to radiotherapy correlated strongly with tumor volume, site of recurrence and total radiation dose. The overall 2 year survival rate was $43\%$ and the disease free survival was $31\%$. Survival rate was significantly influenced by the factors of interval from operation to recurrence, size and site of recurrent tumor, radiation dose, response of radiotherapy, lymph node status as initial presentation, The principal cause of death was lung metastasis($36\%$). Conclusion: Radiotherapy is an excellent modality for control of locoregional recurrent cervix cancer. To improve local control and survival rate, whole pelvic external radiotherapy in addition to ICR with more than 75.0Gy at the depth of 1.0cm from vaginal mucosa is needed and frequent follow up and early detection of recurrence is suggested as well.

• Radiation Oncology Journal
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• v.14 no.3
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• pp.211-219
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• 1996

Purpose : Hysterectomy without lymph node dissection was considered an inadequate treatment method for invasive uterine cervix cancer. Usually the procedure was performed inadvertently on patients who were thought to have benign or premalignant conditions preoperatively. We analysed radiotherapy results of such patients to evaluate survival rates, failure patterns and prognostic factors according to various conditions. Materials and Methods : Sixty one patients undergoing hysterectomy in the presence of invasive cervical carcinoma were reviewed retrospectively. Preoperative diagnosis were carcinoma in situ (38 cases), severe dysplasia (2), myoma (6), uterine bleeding (4), uterine prolapse (2). and early invasive cervix cancer (10) (One patient had myoma and carcinoma in situ coincidently). Patients received postoperative megavoltage radiotherapy from August 1985 to December 1993, and minimum follow-up period was 24 months. Eight patients received ICR only, 6 patients ICR and external radiation, and 47 patients received external radiation therapy only. Results : Overall 5-year survival rate and relapse-free survival rate werer $83.8\%$, $86.9\%$ respectively. For patients with retrospective stage IA, IB, IIB (gross residual after surgery), and vaginal cuff recurrence were $90.9\%$, $88.8\%$, $38.4\%$, and $100\%$ respectively There were 8 cases of treatment failure, most of them (5/8) were in patients with gross residual disease, other patients were full thickness involvement of cervix wall (2/8) except one. Patients with early vaginal cuff recurrence and microinvasive cervical cancer (stage IA) had no treatment related failure Prognostic factors affecting survival by univariate analysis were status of residual disease, tumor histology and retrospective stage. Conclusion : Adjuvant radiotherapy appeared to be effective treatment method for patients with presumed stage IA, IB and early local recurrent disease after inadvertent hysterectomy Survivals for patients with gross disease remained after inappropriate hysterectomy was poor, So, early cancer detection and Proper management with precise pretreatment s1aging is necessary to avoid inadherent hysterectomy especially in the cases of gross residual disease.

• Radiation Oncology Journal
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• v.16 no.3
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• pp.251-258
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• 1998

Purpose : This study was performed to analyze the factors affecting local control in malignant tumors of the parotid gland treated with surgery and postoperative radiation. Materials and methods : Twenty-six patients were treated for malignant tumors of the parotid gland from 1986 to 1995 at Department of Therapeutic Radiology, Chonnam University Hospital. Age of the patients ranged from 14 to 72 years (median : 55 years). Histologically 10 patients of mucoepidermoid carcinoma, 7 of squamous cell carcinoma, 4 of acinic cell carcinoma, 4 of adenoid cystic carcinoma and 1 of adenocarcinoma were treated. Total parotidectomy was performd in 15 of 26 patients, superficial in 7, subtotal in 4. Facial nerve was sacrificed in 5 patients. Postoperatively 4 patients had residual disease, 4 had positive resection margin. Radiation was delivered through an ipsilateral wedged pair of photon in 11 patients. High energy electron beam was mixed with photon in 15 patients. Electron beam dose ranged from 900 cGy to 3800 cGy (median 1700 cGy). Total radiation dose ranged from 5000 cGy to 7560 cGy (median : 6020 cGy). Minimum follow-up period was 2 years. Local control and survival rate were calculated using Kaplan-Meier method. Generalized Wilcoxon test and Cox proportional hazard model were used to test factors affecting local control. Results : Five (19$\%$) of 26 patients had local recurrence. Five year local control rate was 77$\%$. Overall five year survival rate was 70$\%$. Sex, age, tumor size, surgical involvement of cervical lymph node, involvement of resection margin, surgical invasion of nerve, and total dose were analyzed as suggested factors affecting local control rate. Among them patients with tumor size less than 4 cm (p=0.002) and negative resection margin (p=0.011) were associated with better local control rates in univariate analysis. Multivariate analysis showed only tumor size factor is associated with local control rate (p=0.022). Conclusion : This study suggested that tumor size is important in local control of malignant tumors of parotid gland.