• Journal of Yeungnam Medical Science
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• v.24 no.1
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• pp.24-40
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• 2007

Background : Accumulating evidence shows that interleukin(IL)-1 plays a critical role in inflammation and connective tissue destruction observed in both osteoarthritis and rheumatoid arthritis. IL-1 induces gene expression related to cytokines, chemokines and matrix metalloproteinases by activation of many different transcription factors. Materials and Methods : The chondrosarcoma cell line, SW1353, is known to be a valuable in vitro system for investigating catabolic gene regulation by IL-$1{\beta}$ in chondrocytic cells. To explore and analyze the changes in gene expression by IL-1 responsible for arthritis, SW1353 was treated with IL-1 for 1, 6 and 24 h and then total RNAs were purified for each time. The changes in gene expression were analyzed with 17k human cDNA microarrays and validated by semi-quantitative RT-PCR. Results : Greater than a two-fold change was observed in 1,200 genes including metallothioneins, matrix metalloproteinases, extracellular matrix proteins, antioxidant proteins, cytoskeleton proteins, cell cycle regulatory proteins, proteins for cell growth and apoptosis, signaling proteins and transcription factors. These changes appeared to be correlate with the pathophysiological changes observed in early osteoarthritis. Conclusion : cDNA microarray analysis revealed a marked variability in gene expression, and provided insight into the overall molecular changes. The result of this study provide initial information for further studies to identify therapeutic targets in osteoarthritis pathogenesis.

• Radiation Oncology Journal
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• v.17 no.2
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• pp.129-135
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• 1999

Purpose : This study evaluated early bowel complications in cervix cancer patients, following external radiotherapy (ERT and high dose rate intracavitary radiation (HDR ICR). Factors affecting the risk of developing early bowel complications and its incidence are analyzed and discussed Materials and Methods : The study is the retrospective review of 66 patients who received radiotherapy at Chungbuk National University Hospital from April 1994 to December 1998. The patients underwent 41.4 or 50.4 Gy ERT according to FIGO stage and tumor size, then A point dose was boosted to 71.4 or 74.4 Gy using a remotely controlled afterloading Buchler HDR ICR. The EORTC/RTOG morbidity criteria were used to grade early bowel complications, which are valid from day 1, the commencement of therapy, through day 90. The actuarial incidence, severity of complications were investigated and clinical pretreatment factors relevant to complications were found through univariate (Wilcoxon) and multivariate (Cox proportional hazard model) analysis. Results : Of the 66 patients, 30 patients (46$\%$) developed early bowel complications; 25 patients (38$\%$) with grade 1 or 2, 4 patients (0$\%$) with grade 3 and 1 patient (2$\%$) with grade 4. The complications usually began to occur 3 weeks after the commencement of radiotherapy. The actuarial incidence of early bowel complications was 41$\%$ at 10 weeks. The early bowel complications were associated significantly with an old age and a history of previous abdomino-pelvic surgery. All three patients who had a protracted overall treatment time (about 2 weeks) due to severe bowel complication, suffered from pelvic recurrences. Conclusion : Forty six percent of patients experienced early bowel complications, most of which were grade 1 or 2 and relieved spontaneously or by medication. The patients with an old age or a previous surgery have a high probability of early complications and they may be less compliant with planned radiotherapy. So more careful precaution is necessary for these patients.

• The Korean Journal of Nuclear Medicine
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• v.38 no.1
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• pp.52-61
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• 2004

Purpose: Cervical lymph node metastasis is the most important factor of the prognosis and therapeutic planning in head and neck cancer. With increasing interest of minimally invasive neck surgery, more accurate preoperative assessment of cervical lymph node becomes more essential. We evaluated the diagnostic accuracy of $^{18}F$ FDG-PET in the assessment of lymph node metastasis in patients with primary head and neck cancer and compared the results with those of CT/MRI. Materials and Methods: Thirty-two patients (M/F=27/5, $56{\pm}10yr$) with biopsy proven head and neck cancer (16 supraglottic cancer, 9 tongue cancer, 7 others) underwent FDG-PET and CT/MRI (25/7) within 1 month before neck dissection. Based on lymph node level, the diagnostic sensitivity and specificity of FDG PET and CT/MRI for the metastasis of cervical lymph node were compared. Results: Of 153 lymph node levels dissected in 32 patients, 32 lymph node levels of 19 patients were positive for metastasis by histopatholologic examination. The overall sensitivity and specificity of FDG-PET were 88% (28/32) and 93% (113/121), whereas those of CT/MRI were 56% (18/32) (p=0.002) and 92% (112/121), respectively. The diagnostic sensitivity and specificity of FDG-PET were different according to location of lymph node levels, and those of ipsilateral level 11 were lower than those of other levels. Conclusion: FDG-PET is more sensitive in detecting metastatic cervical lymph node in head and neck cancer than CT/MRI. FDG-PET might be useful in guiding the extent of neck dissection.

• The Korean Journal of Nuclear Medicine Technology
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• v.12 no.1
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• pp.49-56
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• 2008

Purpose: Whole body imaging with radioiodine can detect functioning metastases. Non-physiologic I-131 uptake detected on images usually is interpreted as suggesting functioning thyroid metastases. However, extra-thyroidal I-131 accumulation does not always imply thyroid cancer metastases and has been reported in many circumstances. In order to avoid unnecessary therapeutic interventions it is important to distinguish false-positive sites of I-131 localization. We study here to remove false-positive sites around esophagus region on I-131 whole body imaging in patients who were administrated thyroidectomy. Materials and Methods: From April to August in 2007, we had the patients who had visited our department after they received thyroidectomy due to thyroid cancer. They were given I-131, and performed radioiodine body scan after 41 to 50 hours. Patients were whole-body-scanned for the speed of 8 cm per minute. After that, we took anterior and posterior static images around the patients' neck measured by 300 thousand counts per image. We selected 44 patients who had hot spots around neck region, we divided the patients into two groups. One group was given 0.5 L of water and the other group was given 0.5 L of water with 1 g of Vitamin C dissolved. The patients were asked to drink the fluid for one minute in sitting position and after that, we measured 300 kilo counts per image again. We compared prior anterior, posterior static images with anterior, posterior images after the patients had water or water that Vitamin C resolved. Results: In using water, both observer 1 and 2 interpreted 6 patients were washed out. In the water with Vitamin C resolved, observer 1 and 2 interpreted 9 and 8 patients were washed out. Observer 1 and 2 interpreted 6 and 5 patients had 'indeterminate' when they used water. Both observer 1 and 2 interpreted 6 patients had 'indeterminate' when they used water with Vitamin C resolved. When they used water, observer 1 interpreted 10 patients had 'unchanged' and observer 2 interpreted 11 patients had 'unchanged'. Differently, when they used water with vitamin C resolved, observer1 had 8 patients having 'unchanged'and observer 2 had 9. Conclusion: As a result, by making patients drink 0.5 liter of water which has vitamin C resolved helped getting rid of false-positive sites in esophagus. Therefore, based on this study, we believe that drinking water with vitamin C dissolved is very in terms of reducing false-positive hot spot around the esophagus for the iodine-131 whole body scan.

• Radiation Oncology Journal
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• v.20 no.4
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• pp.309-315
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• 2002

Purpose : To evaluate the result of conservative management on recurrence, survival and prognostic factors of patient with operable breast cancer. Materials and Methods : Fifty three patients, treated for localized breast cancer by lumpectomy or quadrantectomy followed by radiotherapy between January 1985 and December 1996, were retrospectively studied. All patients followed up for at least five years. Their median age was 43 years $(range\;24\~72)$. The tumor stages were as follows : T1 in 30 patients, T2 in 21, Tis in 2. Thirty-eight patients had negative and 15 had positive axillary nodes. The histological types were 42 infiltrating ductal, 2 infiltrating lobular, and 2 intraductal carcinomas with 7 other histologies. The tumor locations were the outer quadrant in 38 breasts, the inner quadrant in 13 and central in 2. Radiation doses of $46\~50\;Gy$ were given to the entire breast areas with additional doses of 14-18 Gy delivered to the tumor bed areas. Results : The overall five and 10 yea actuarial and disease free survivals were $94.3\%\;and\;92.4\%,\;91.2\%\;and\;81\%$, respectively. The overall five year survivals were $100\%$ in stage I and IIa, and $66.7\%$ in stage IIb and IIIa tumors. Seven patients failed either locally or distantly. Incidence of local failure and distant metastasis for the first failure were $7.5\%\;and\;5.7\%$, respectively. Local recurrence appeared within 2 years of treatment at the primary site and after more than 8 years outside of primary lesion, whereas distant metastasis appeared between 2 and 6 years following treatment. The overall recurrences were high at a young age (< or = 35 years), with 5 out of 12 (2 local, 3 distant), and in T2 lesions with 5 out of 21 (1 local, 3 distant, and 1 in both). Distant metastasis was high in the positive axillary lymph node group with 4 out of 15 $(26.6\%)$. A high incidence in the axillary node was noted at a young age with 7 out of 12 $(58.3\%)$ and in T2 lesions with 8 out of 21 $(38.4\%)$. A young age, positive axillary node and large tumor size were all related with poor survival. Conclusion : Based on this study, lumpectomy or quadrantectomy, followed by radiation appears to be an adequate therapeutic method in operable breast cancer. A long term follow-up is necessary because a recurrence of breast can occur long time after treatment. The poor prognostic group, especially young patients with an aggressive biological behavior needs more effective treatment modalities to improve their survival.

• Radiation Oncology Journal
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• v.13 no.4
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• pp.403-409
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• 1995

Purpose : Authors tried to enhance the safety and accuracy of radiosurgery by verifying stereotacitc target point in actual treatment position prior to irradiation. Materials and Methods : Before the actual treatment, several sections of anthropomorphic head phantom were used to create a condition of unknown coordinates of the target point. A film was sandwitched between the phantom sections and punctured by sharp needle tip. The tip of the needle represented the target point. The head phantom was fixed to the stereotactic ring and CT scan was done with CT localizer attached to the ring. After the CT scanning, the stereotactic coordinates of the target point were determined. The head phantom was secured to accelerator's treatment couch and the movement of laser isocenter to the stereotactic coordinates determined by CT scanning was performed using target positioner. Accelerator's anteroposterior and lateral portal films were taken using angiographic localizers. The stereotactic coordinates determined by analysis of portal films were compared with the stereotactic coordinates previously determined by CT scanning. Following the correction of discrepancy the head phantom was irradiated using a stereotactic technique of several arcs. After the irradiation, the film which was sandwitched between the phantom sections was developed and the degree of coincidence between the center of the radiation distribution with the target point represented by the hole in the film was measured. In the treatment of the actual patients, the way of determining the stereotactic coordinates with CT localizers and angiograuhic localizers was the same as the phantom study. After the correction of the discrepancy between two sets of coordinates, we proceeded to the irradiation of the actual patient. Results : In the phantom study, the agreement between the center of the radiation distribution and the localized target point was very good. By measuring optical density profiles of the sandwitched film along axes that intersected the target point, authors could confirm the discrepancy was 0.3 mm. In the treatment of an actual patient, the discrepancy between the stereotactic coordinates with CT localizers and angiographic localizers was 0.6 mm. Conclusion : By verifying stereotactic target point in actual treatment position prior to irradiation, the accuracy and safety of streotactic radiosurgery procedure were established.

• Radiation Oncology Journal
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• v.23 no.4
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• pp.211-216
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• 2005

Purpose: It has been reported that all-trans retinoic acid (ATRA) can inhibit glioma growing in vitro. However, clinical trials with ATRA alone in gliomas revealed modest results. ATRA has been shown to increase radiosensitivity in other tumor types, so combining radiation and ATRA would be one of alternatives to increase therapeutic efficacy in malignant gliomas. Thus, we intended to know the role of catalase, which is induced by ATRA, for radiosensitivity if radiation-reduced reactive oxygen species (ROS) is removed by catalase, the effect of radiation will be reduced. Materials and Methods: A rat glioma cell line (36B10) was used for this study. The change of catalase activity and radiosensitivity by ATRA, with or without 3-amino-1, 2, 4-triazole (ATZ), a chemical inhibitor of catalase were measured. Catalase activity was measured by the decomposition of $H_2O_2$ spectrophotometrically Radiosensitivity was measured with clonogenic assay. Also ROS was measured using a 2, 7-dichlorofluorescein diacetate spectrophotometrically. Results: When 36B10 cells were exposed to 10, 25 and $50{\mu}M$ of ATRA for 48 h, the expression of catalase activity were increased with increasing concentration and incubation time of ATRA. Catalase activity was decreased with increasing the concentration of AT (1, $10{\mu}M$) dose-dependently. ROS was increased with ATRA and it was augmented with the combination of ATRA and radiation. ATZ decreased ROS production and increased cell survival in combination of ATRA and radiation despite the reduction of catalase. Conclusion: The increase of ROS is one of the reasons for the increased radiosensitivity in combination with ATRA. The catalase that is induced by ATRA doesn't decrease ROS production and radiosensitivity.

• Radiation Oncology Journal
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• v.21 no.2
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• pp.149-157
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• 2003

Purpose: The purpose of this study was to determine if there were prognostic differences between BRCA related and BRCA non-related Korean patients with early-onset breast carcinomas. Materials and Methods: Sixty women who had developed breast cancers before the age of 40, and who were treated at the Soonchunhyang University Hospital, were studied independently of their family histories. The age range was 18 to 40 with a median of 34.5 years. Lymphocyte specimens from peripheral blood were studied for the heterozygous mutations of BRCA1 and BRCA2 using direct sequencing methods. Immunohistochemistry was peformed on the paraffin-embedded tissue blocks that were available. Results: Eleven deleterious mutations (18.3%, 6 in BRCA1 and 5 in BRCA2) and 7 missense mutations of unknown significance (11.7%), were found among the 60 patients. More than half of the mutation were novel, and were not reported in the database. Most of the BRCA-associated patients had no history of breast cancer. No treatment related failures were observed in the BRCA carriers, with the exception of one patient that had experienced a new primary tumor of the contralateral breast. The seven year relapse free survival rate were 50 and 79% In the BRCA carrier and BRCA negative patients, respectively. Although the expression of estrogen and progesterone receptors were less common, and histological features more aggressive, in the BRCA associated tumors, the outcome of the patients with BRCA mutations was not poorer than that on the patients without deleterious mutations. Conclusion.: Despite the BRCA mutation carriers having adverse prognostic features, the recurrence rate was relatively lower than that in the BRCA non-carrying Korean patients wi4h early-onset breast carcinomas. In addition, although the prevalence of the BRCA mutation in Korean patients was higher than that in white patients, the penetrance of the cancer seemed to be relatively low in Korean women carrying BRCA mutations. A large population based study of the BRCA mutation, with a long-term follow-up of the study patients will be required to confirm these results.

• Nuclear Medicine and Molecular Imaging
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• v.43 no.5
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• pp.478-486
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• 2009

Purpose: 5-iododeoxyuridine analogues have been exclusively developed for the potential antiviral and antitumor therapeutic agents. In this study, we synthesized carbocyclic radioiododeoxyuridineanalogue (ddIVDU) and carbocyclic intermediate as efficient carbocyclic radiopharmaceuticals. Materials and Methods: The synthesis is LAH reduction, hetero Diels-Alder reaction as key reactions including Pd(0)-catalyzed coupling reaction together with organotin. MCA-RH7777 (MCA) and MCA-tk (HSV1-tk positive) cells were treated with various concentration of carbocyclic ddIVDU, and GCV. Cytotoxicity was measured by the MTS methods. For in vitro uptake study, MCA and MCA-tk cells were incubated with 1uCi of [$^{125}I$]carbocyclic ddIVDU. Accumulated radioactivity was measured after various incubation times. Results: The synthesis of ddIVDU and precursor for radioiodination were achieved from cyclopentadiene in good overall yield, respectively. The radioiododemetallation for radiolabeling gave more than 80% yield with > 95% radiochemical purity. GCV was more toxic than carbocyclic ddIVDU in MCA-tk cells. Accumulation of [$^{125}I$]carbocyclic ddIVDU was higher in MCA-tk cells than MCA cells. Conclusion: Biological data reveal that ddIVDU is stable in vitro, less toxic than ganciclovir (GCV), and selective in HSV1-tk expressed cells. Thus, this new carbocyclic nucleoside, referred to in this paper as carbocyclic 2',3'-didehydro-2',3'-dideoxy-5- iodovinyluridine (carbocyclic ddIVDU), is a potential imaging probe for HSV1-tk.

• Nuclear Medicine and Molecular Imaging
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• v.43 no.5
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• pp.395-401
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• 2009

Purpose: We evaluated $^{18}F$-FDG PET/CT findings in initially diagnosed adenoid cystic carcinoma (ACC) of the head and neck in association with pathological subtype, staging, uptake comparison with squamous cell carcinoma (SqCC) and prognosis. Materials and Methods: The subjects were 16 patients with initially diagnosed ACC of head and neck who underwent pretreatment $^{18}F$-FDG PET/CT. Histological subtype (solid pattern vs. tubular/cribriform pattern), $SUV_{max}$ of size-matched SqCC of the head and neck as control group, disease-free survival (DFS) were compared with the $SUV_{max}$ of ACC of the head and neck. Results: Of total 16 patients, 6 had solid pattern and the remaining 10 had tubular/cribriform pattern. The $SUV_{max}$ were significantly higher in solid pattern group than in tubular/cribriform pattern group ($6.7{\pm}3.2$ vs. $4.2{\pm}0.9$, p=0.03). PET/CT found unexpected distant metastasis in 18.7% of patients (3/16) and changed the therapeutic plan in those patients. The $SUV_{max}$ of ACC was significantly lower than that of size-matched SqCC ($5.1{\pm}2.4$ vs. $13.6{\pm}6.0$, p<0.001). DFS was not significantly different according to the histological subtype. In contrast, patients with high $^{18}F$-FDG uptake ($SUV_{max}$ ${\geq}$6.0) had significantly shorter DFS than those with low $^{18}F$-FDG uptake ($SUV_{max}$ <6.0). Conclusion: $^{18}F$-FDG uptake of ACC of the head and neck is significantly associated with histological subtype and DFS. $^{18}F$-FDG PET/CT may be useful for detecting unexpected metastasis. Since $^{18}F$-FDG uptake of tubular/cribriform ACC compared with SqCC is relatively low, it is necessary to interpret PET images carefully in patients without alleged ACC.