• Journal of Radiation Protection and Research
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• 제20권2호
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• pp.97-102
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• 1995

인체 말초 혈액 림프구에서 저선량의 감마선에 의해 유도되는 적응 반응을 관찰하였다. 인체 림프구를 저선량의 감마선(priming dose 0.01Gy) 을 조사한 후 여러 시간 간격 후 고선량 (challenging dose, 1.5Gy) 을 조사하였다. 저선량을 미리 조사한 림프구와 조사하지 않은 림프구에서 발생된 미세핵의 빈도를 계수하였다. 비세핵 발생 빈도는 저선량 조사 4시간 후 고선량을 조사하였을 때 최대 감소치를 보였다. 저선량과 고선량 조사 시간차가 7시간 또는 20시간이었을 때 미세핵 발생 빈도는 약간 감소하였으나 유의성은 없었다. 본 연구에서는 $G_0$상태의 세포주기에서 저선량을 조사하였을 경우 적응 반응이 나타나는 것이 관찰 되었다. 미세핵 분석법은 실험 방법이 비교적 간단하고, 기타 염색체 분석법에 비하여 빠른 시간내 결과를 도출 할 수 있어 추후 방사선에 대한 적응 반응의 연구에 유용한 지표가 될 수 있을 것이다.

• Journal of Microbiology and Biotechnology
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• 제21권4호
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• pp.438-447
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• 2011

Deinococcus radiodurans is extremely resistant to various genotoxic conditions and chemicals. In this study, we characterized the effect of a sublethal concentration (100 ${\mu}M$) of cadmium (Cd) on D. radiodurans using a whole-genome DNA microarray. Time-course global gene expression profiling showed that 1,505 genes out of 3,116 total ORFs were differentially expressed more than 2-fold in response to Cd treatment for at least one timepoint. The majority of the upregulated genes are related to iron uptake, cysteine biosynthesis, protein disulfide stress, and various types of DNA repair systems. The enhanced upregulation of genes involved in cysteine biosynthesis and disulfide stress indicate that Cd has a high affinity for sulfur compounds. Provocation of iron deficiency and growth resumption of Cd-treated cells by iron supplementation also indicates that CdS forms in iron-sulfur-containing proteins such as the [Fe-S] cluster. Induction of base excision, mismatch, and recombinational repair systems indicates that various types of DNA damage, especially base excision, were enhanced by Cd. Exposure to sublethal Cd stress reduces the growth rate, and many of the downregulated genes are related to cell growth, including biosynthesis of cell membrane, translation, and transcription. The differential expression of 52 regulatory genes suggests a dynamic operation of complex regulatory networks by Cd-induced stress. These results demonstrate the effect of Cd exposure on D. radiodurans and how the related genes are expressed by this stress.

• Radiation Oncology Journal
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• 제13권4호
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• pp.339-348
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• 1995

목적 : 위암의 간문맥 임파절 재발로 발생한 악성 폐쇄성 황달치료에 있어서 외부 방사선치료의 효과를 평가해 보고 치료의 결과에 영향을 미칠 수 있는 요인을 알아보고자 하였다. 방법 : 1984년부터 1993년까지 위암의 간문맥 전이로 악성 폐쇄성 황달이 발생한 32명중 3000cGy이상의 방사선량이 조사된 23명을 대상으로 하였다. 치료 결과에 영향을 미칠 수 있는 요인을 알아보기 위하여 방사선량, 황달발생 당시의 질병의 진전정도 및 황달을 일으키는 종피의 위치, 방사선치료 전 총 bilirubin치, 다른 치료와의 병합여부, 원발병소의 수술정도, 재발전 병기를 분석하였다. 외부 방사선치료는 4백만 전자볼트 선형가속기를 이용하여 주 5회, 1회 180-300cGy를 간문맥을 포함하는 부위에 3000cGy-5480cGy(중앙값 3770cGy,TDF 49-86 3420cGy-5580cGy 중앙값 TDF 65, 4140cGy/23fx)가 조사되었다. TDF 65(4140cGy/23fx 이상과 미만을 받은 환자는 각각 13, 10명이었다. 결과 : 전체 환자 23명중 완전관해 13명, 부분관해 5명, 무반응 5명이었다. 전체 환자의 중앙 생존 기간은 5개월이나 완전관해의 경우는 11개월이고 부분관해와 무반응의 경우 각각 3개월이었다. 완전관해를 보인 13명중 6명이 1년 이상 생존하였다. 완전관해의 경우와 부분관해, 무반응과의 생존 기간의 비교에서 의미있는 차이를 보였다(p<0.05). TDF 65인 4140cGy 이상을 받은 13명중 완전관해, 부분관해, 무반응이 각각 10, 2, 1명이었다. 이들 전체환자의 중앙 생존 기간은 9.5개월 이었고 완전관해를 이룬경우 11.5개월 이었다. 그러나 TDF 65(4140cGy/23fx) 미만을 받은 10명중 완전관해, 부분관해, 무반응이 각각 3, 3, 4명 이었고 이들의 중앙 생존 기간은 4.3개월 이었다. 따라서 방사선량이 치료 결과에 영향을 미치며 완전관해를 이루기 위해서는 TOF 65(4140cGy/23fx)이상이 조사되어야 할 것이다. 치료시 질병의 진전정도는 완전관해를 보인 경우 7명이 간문맥이나 췌장 주위에만 국한된 병변을가졌고(5명 담도계하부 병변) 무반응과 부분반응을 보인 모든 환자는 광범위한 질병의 진전이 있거나, 일차병변의 지속상태였다. 질병의 진전상태가 국소적일수록, 담도계하부에 국한되어 있을수록 완전관해의 가능성이 높고 1년 이상 장기생존이 가능할 것으로 추정된다. 완전관해인 경우 10명이 방사선치료후 계속적인 항암화학요법을 받았고 이들중 6명이 1년 이상 생존하였다. 치료 결과에 영향을 미칠 것으로 추정되는 요인으로 방사선량, 황달 발생당시 질병의 진전정도 및 황달을 일으키는 종괴의 위치로 분석 되었다. 외부 방사선치료중 경미한 위장관 부작용(오심, 구토)이 발생하였으나 방사선치료 시행에 영향을 미치지 않았다. 결론 : 위암의 재발로 인해 발생한 악성 폐쇄성 황달환자의 치료에 있어서 TDF 65(4140cGy/23fx) 이상의 외부 방사선치료 단독으로도 만족할 만한 고식적 효과를 이룰수 있고 방사선량과 재발 당시 질병의 진전정도가 치료 결과에 영향을 미칠 수 있는 요인으로 생각 된다.

• Radiation Oncology Journal
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• 제34권1호
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• pp.34-44
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• 2016

Purpose: A prospective phase II trial was conducted to evaluate the effectiveness and toxicity of regional hyperthermia and whole liver irradiation (WLI) for numerous chemorefractory liver metastases from colorectal cancer. Materials and Methods: Enrolled patients had numerous chemorefractory hepatic metastases from colorectal cancer. Five sessions of hyperthermia and seven fractions of 3-gray WLI were planned. Health-related quality of life (HRQoL) was determined using the Korean version of the European Organization for Research and Treatment of Cancer quality of life questionnaire C-30 and the Functional Assessment of Cancer Therapy-Hepatobiliary version 4.0. Objective and pain response was evaluated. Results: A total of 12 patients consented to the study and the 10 who received WLI and hyperthermia were analyzed. WLI was completed as planned in nine patients and hyperthermia in eight. Pain response was partial in four patients and stable in four. Partial objective response was achieved in three patients (30.0%) and stable disease was seen in four patients at the 1-month follow-up. One patient died 1 month after treatment because of respiratory failure related to pleural metastasis progression. Other grade III or higher toxicities were detected in three patients; however, all severe toxicities were related to disease progression rather than treatment. No significant difference in HRQoL was noted at the time of assessment for patients who were available for questionnaires. Conclusion: Combined WLI and hyperthermia were well tolerated without severe treatment-related toxicity with a promising response from numerous chemorefractory hepatic metastases from colorectal cancer.

• Journal of Korean Neurosurgical Society
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• 제66권5호
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• pp.562-572
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• 2023

Objective : Bevacizumab is a feasible option for treating cerebral radiation necrosis (RN). We investigated the clinical outcome of RN after treatment with bevacizumab and factors related to the initial response and the sustained effect. Methods : Clinical data of 45 patients treated for symptomatic RN between September 2019 and February 2021 were retrospectively collected. Bevacizumab (7.5 mg/kg) was administered at 3-week intervals with a maximum four-cycle schedule. Changes in the lesions magnetic resonance image (MRI) scans were examined for the response evaluation. The subgroup analysis was performed based on the initial response and the long-term maintenance of the effect. Results : Of the 45 patients, 36 patients (80.0%) showed an initial response, and eight patients (17.8%) showed delayed worsening of the corresponding lesion. The non-responders showed a significantly higher incidence of diffusion restriction on MRI than the responders (100.0% vs. 25.0%, p<0.001). The delayed worsening group showed a significantly higher proportion of glioma pathology than the maintenance group (87.5% vs. 28.6%, p=0.005). Cumulative survival rates with sustained effect were significantly higher in the groups with non-glioma pathology (p=0.019) and the absence of diffusion restriction (p<0.001). Pathology of glioma and diffusion restriction in MRI were the independent risk factors for non-response or delayed worsening after initial response. Conclusion : The initial response of RN to bevacizumab was favorable, with improvement in four-fifths of the patients. However, a certain proportion of patients showed non-responsiveness or delayed exacerbations. Bevacizumab may be more effective in treating RN in patients with non-glioma pathology and without diffusion restriction in the MRI.

• Radiation Oncology Journal
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• 제33권4호
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• pp.276-283
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• 2015

Purpose: We evaluated the efficacy and toxicity of repeated high dose 3-dimensional conformal radiation therapy (3D-CRT) for patients with unresectable hepatocellular carcinoma. Materials and Methods: Between 1998 and 2011, 45 patients received hepatic re-irradiation with high dose 3D-CRT in Samsung Medical Center. After excluding two ineligible patients, 43 patients were retrospectively reviewed. RT was delivered with palliative or salvage intent, and equivalent dose of 2 Gy fractions for ${\alpha}/{\beta}=10Gy$ ranged from $31.25Gy_{10}$ to $93.75Gy_{10}$ (median, $44Gy_{10}$). Tumor response and toxicity were evaluated based on the modified Response Evaluation Criteria in Solid Tumors criteria and the Common Terminology Criteria for Adverse Events (CTCAE) ver. 4.0. Results: The median follow-up duration was 11.2 months (range, 4.1 to 58.3 months). An objective tumor response rate was 62.8%. The tumor response rates were 81.0% and 45.5% in patients receiving ${\geq}45Gy_{10}$ and $<45Gy_{10}$, respectively (p = 0.016). The median overall survival (OS) of all patients was 11.2 months. The OS was significantly affected by the Child-Pugh class as 14.2 months vs. 6.1 months (Child-Pugh A vs. B, p < 0.001), and modified Union for International Cancer Control (UICC) T stage as 15.6 months vs. 8.3 months (T1-3 vs. T4, p = 0.004), respectively. Grade III toxicities were developed in two patients, both of whom received ${\geq}50Gy_{10}$. Conclusion: Hepatic re-irradiation may be an effective and tolerable treatment for patients who are not eligible for further local treatment modalities, especially in patients with Child-Pugh A and T1-3.

• BMB Reports
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• 제34권2호
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• pp.123-129
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• 2001

Cellular response to ionizing radiation is affected by cell types, radiation doses, and post-irradiation time. Based on the trypan blue dye exclusion assay in normal oral mucosal cells (OM cells), a 48 h post-irradiation was sufffcient and an adequate time point for the evaluation of radiation sensitivity Its $LD_{50}$ was approximately 1.83 Gy To investigate possible biomarkers useful for the biological radiodosimetry of normal epithelial cells (p53, c-fos, cyclin D1, cdc-2, pRb) EGF receptor phosphorylation and Erk activation were evaluated at different radiation doses and different post-irradiation times. From 0.5 Gy, p53 was accumulated in the nucleus of basal cells of the OM raft culture at 4 h post-irradiation and sustained up to 24 h post-irradiation, which suggests that radiation-induced apoptosis or damage repair was not yet completed. The number of p53 positive cells and biosynthesis of p53 were correlated with radiation doses. Both cyclin D1 and c-fos were only transiently induced within 1 h post-irradiation. Cyclin D1 was induced at all radiation doses. However, cfos induction was highest at 0.1 Gy, approximately 7.3 fold more induction than the control, whose induction was reduced in a reverse correlation with radiation dose. The phosphorylation pattern of cdc-2 and pRb were unaffected by radiation. In contrast to A431 tails overexpressing the EGF receptor approximately 8.5 fold higher than normal epithelial, the OM cells reduced the basal level of the EGF receptor phosphorylation in a radiation dose dependent fashion. In conclusion, among radiation-induced biomolecules, the p53 nuclear accumulation may be considered for the future development of a useful marker far biological radiodosimetry in normal epithelial tissue since it was sustained for a longer period and showed a dose response relationship. Specific c-fos induction at a low dose may also be an important finding in this study It needs to be studied further for the elucidation of its possible connection with the low dose radio-adaptive response.

• 대한방사선협회지
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• 제25권1호
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• pp.317-323
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• 1999

The response of endothelial cells to ionizing radiation is thought to be an important factor in the overall response of normal tissue. It has been reported that basic fibroblast growth factor (bFGF), a potent mitogen for endothelial cells, protects endoth

• Radiation Oncology Journal
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• 제38권2호
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• pp.119-128
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• 2020

Purpose: Colorectal cancer is becoming an increasing concern in the middle-aged population of Iran. This study aimed to compare the preliminary results of short-course and long-course neoadjuvant chemoradiotherapy treatment for rectal cancer patients. Materials and Methods: In this clinical trial we recruited patients with rectal adenocarcinoma located from 5 cm to 15 cm above the anal verge. Patients in group I (short-course) received three-dimensional conformational radiotherapy with a dose of 25 Gy/5 fractions in 1 week plus concurrent XELOX regimen (capecitabine 625 mg/㎡ from day 1-5 twice daily and oxaliplatin 50 mg/㎡ on day 1 once daily). Patients in group II (long-course) received a total dose of 50-50.4 Gy/25-28 fractions for 5 to 5.5 weeks plus capecitabine 825 mg/㎡ twice daily. Both groups underwent consolidation chemotherapy followed by delayed surgery at least 8 weeks after radiotherapy completion. The pathological response was assessed with tumor regression grade. Results: In this preliminary report on complications and pathological response, 66 patients were randomized into two study groups. Mean duration of radiotherapy in the group II (long-course) was 5 ± 1 days (range, 5 to 8 days) and 38 ± 6 days (range, 30 to 58 days). The median follow-up was 18 months. Pathological complete response was achieved in 32.3% and 23.1% of patients in the shortcourse and long-course groups, respectively (p = 0.558). Overall, acute grade 3 or higher treatment-related toxicities occurred in 24.2% and 22.2% of patients in group I and II, respectively (p = 0.551). No acute grade 4 or 5 adverse events were observed in either group except one grade 4 hematologic toxicity that was seen in group II. Within one month of surgery, no significant difference was seen regarding grade ≥3 postoperative complications (p = 0.333). Conclusion: For patients with rectal cancer located at least 5 cm above the anal verge, short-course radiotherapy with concurrent and consolidation chemotherapy and delayed surgery is not different in terms of acute toxicity, postoperative morbidity, complete resection, and pathological response compared to long-course chemoradiotherapy.

• Archives of Pharmacal Research
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• 제21권6호
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• pp.640-644
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• 1998

AT cells exhibit defective cell cycle regulation following DNA damage. Previous studies have shown that induction of p53 and p2i proteins are delayed in response to ionizing rad iation, resulting in the failure of G1/S checkpoint in AT cells. In this study, further investigation of the molecular mechanisms underlying G1/S phase progression in AT cells was conducted. Exponentially growing normal and AT cells were exposed to 2 Gly of ionizing radiation and the expression levels and functional activities of Rb and E2F-1 proteins were determined. We observed overexpression of hyperphosphorylated Rb and E2F-1 proteins in AT cells, which was unaffected post-irradiation. Furthermore, gel shift assays showed that E2F-1-DNA binding was constitutive in AT cells, whereas it was inhibited in control cells following exposure to ionizing radiation. The data suggests that abnormalities in the function of Rb and E2F-1 proteins may also be responsible for the failure of AT cells to arrest in the G1/S checkpoint in response to DNA damage.