Different Expressions of HIF-1α, Bcl-2 and Baxin DU145 Prostate Cancer Cells Transplanted in Nude Mouse between X-Ray and Neutron Irradiation

Moonkyoo Kong(공문규),Jin Oh Kang(강진오),Sang Ki Kim(김상기),Dong Oh Shin(신동오),Seo Hyun Park(박서현),Chang Ju Kim(김창주),Hyun Kyung Chang(장현경) 대한방사선종양학회 2009 Radiation Oncology Journal Vol.27 No.4

Purpose: To investigate the radiobiologic effects of neutron and X-ray irradiation on DU-145 prostate carcinoma cells by identifying the differences of HIF-1α expression and apoptosis. Materials and Methods: Nude mice were injected with the human prostate cancer cell line, DU-145, and then irradiated with 2 Gy and 10 Gy X-rays, or 0.6 Gy and 3.3 Gy neutrons, respectively. The mice were sacrificed at 24 hours and 120 hours after irradiation. The expression levels of HIF-1α, Bcl-2 and Bax were compared with immunohistochemical staining and western blotting. The apoptotic indexes were compared with the Terminal deoxynucleotidyl biotin-dUTP nick and labeling (TUNEL) assay. Results: At day 1, HIF-1α and Bcl-2 expression decreased, while Bax expression and the number of TUNEL positive cells increased in neutron irradiated groups for the control and X-ray irradiated groups. The Bcl-2/Bax ratio was significantly lower in the neutron irradiated groups regardless of dose (p=0.001). The same pattern of the differences in the expressions of the HIF-1α, Bcl-2, Bax, Bcl-2/Bax ratio, and apoptotic indexes were indentified at day 5. HIF-1α expression was related with Bcl-2 (p=0.031), Bax (p=0.037) expressions and the apoptotic indexes (p=0.016) at day 5. Conclusion: Neutron irradiation showed a decrease in HIF-1α, Bcl-2 expression, and Bcl-2/Bax ratio, but increased Bax expression regardless of dose. This study suggests that the differences radiobiological responses between photon and neutron irradiation may be related to different HIF-1α expression and subsequent apoptotic protein expressions. 목 적: 전립샘암 세포주 DU 145에서 엑스선과 중성자선에 의한 HIF-1α와 아포프토시스 발현의 차이를 비교함으로써 엑스선과 중성자선의 방사선생물학적 차이의 기전을 알아보고자 한다. 대상 및 방법: 누드 마우스에 DU 145 전립샘암 세포주를 주입한 후 2 Gy 엑스선, 10 Gy 엑스선, 0.6 Gy 중성자선, 3.3 Gy 중성자선을 각각 조사했다. 엑스선을 조사한 군과 중성자선을 조사한 군에서 HIF-1α, Bcl-2, Bax, 아포프토시스 발현 정도를 면역조직화학 염색과 western blotting을 이용하여 비교하였다. 아포토시스의 정도는 terminal deoxynucleotidyl biotin-dUTP nick end labeling (TUNEL) 염색을 이용하여 비교하였다. 결 과: 방사선 조사 1일째, X선을 조사한 군과 비교했을 때, 중성자선을 조사한 군에서 HIF-1α와 Bcl-2의 발현은 감소하였고, Bax와 아포프토시스 세포의 수는 증가하였다. Bcl-2/Bax 비는 중성자선을 조사한 군에서 의미 있게 감소하였다. 이러한 HIF-1α, Bcl-2, Bax, Bcl-2/Bax 비, 아포프토시스 발현의 차이는 방사선 조사 5일째에도 동일하게 유지되어 나타났다. 또한, HIF-1α 발현은 방사선 조사 5일째 Bcl-2 (p=0.031), Bax (p=0.037), TUNEL (p=0.016) 발현과 연관성을 보였다. 결 론: 중성자선 조사한 경우 엑스선에 비해 HIF-1α와 Bcl-2 발현, Bcl-2/Bax 비가 감소하고, Bax 발현은 증가하였다. 중성자선 치료의 광자선과 다른 방사선생물학적인 반응은 HIF-1α와 그로 인한 아포프토시스 관련 단백질 발현의 차이와 연관성이 있을 것으로 생각한다.

The Efficacy and Safety of Jaungo, a Traditional Medicinal Ointment, in Preventing Radiation Dermatitis in Patients with Breast Cancer: A Prospective, Single-Blinded, Randomized Pilot Study

Kong, Moonkyoo,Hwang, Deok-Sang,Lee, Jee Young,Yoon, Seong Woo Hindawi Publishing Corporation 2016 Evidence-based Complementary and Alternative Medic Vol.2016 No.-

<P><I>Purpose</I>. This study was performed to evaluate the efficacy and safety of Jaungo in preventing radiation dermatitis in patients with breast cancer.<I> Methods</I>. Thirty patients were prospectively enrolled and randomly assigned to receive Jaungo or general supportive skin care. Radiation dermatitis and pain were examined at daily intervals from the start of radiotherapy until 4 weeks after its completion. The primary endpoint of this study was the incidence of radiation dermatitis. The secondary endpoints were time to onset of radiation dermatitis, duration of radiation dermatitis, and maximum pain score.<I> Results</I>. Jaungo reduced the incidence of grade ≥2 (46.7% versus 78.6%) and grade 3 radiation dermatitis (20.0% versus 50.0%) in comparison with general supportive skin care. Jaungo also delayed the onset of grade 2 dermatitis (35 days versus 30 days). In terms of time to onset of grade 3 dermatitis, duration of dermatitis, and maximum pain score, Jaungo showed results comparable to those achieved with general supportive skin care. No patients experienced adverse effects caused by Jaungo administration.<I> Conclusions</I>. Jaungo minimized radiation dermatitis in patients with breast cancer without causing adverse effects. Further randomized studies with a larger sample size are required to assess clinical use of Jaungo.</P>

Topical Use of Recombinant Human Epidermal Growth Factor (EGF)-Based Cream to Prevent Radiation Dermatitis in Breast Cancer Patients: a Single-Blind Randomized Preliminary Study

Kong, Moonkyoo,Hong, Seong Eon Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.8

Background: The purpose of this study was to assess the effectiveness of a recombinant human epidermal growth factor (EGF)-based cream for the prevention of acute radiation dermatitis in breast cancer patients receiving radiotherapy (RT). Materials and Methods: Between December 2012 and April 2013, 40 breast cancer patients who received postoperative RT were prospectively enrolled in this study and randomly assigned to receive human recombinant EGF-based cream (intervention group) or general supportive skin care (control group). The grade of radiation dermatitis and pain score were examined at weekly intervals during RT and 6 weeks after RT completion. Results: All patients completed the planned RT and complied well with instructions for applying the study cream and general supportive skin care. In the intervention group, radiation dermatitis of maximum grade 3, 2, and 1 developed in 3 (15%), 11 (55%), and 6 patients (30%), respectively. In comparison, in the control group, radiation dermatitis of maximum grade 3, 2, and 1 developed in 8 (40%), 10 (50%), and 2 patients (10%), respectively. The intervention group showed lower incidence of grade 3 radiation dermatitis than the control group (p=0.068 in univariate analysis and p=0.035 in multivariate analysis). There was no statistically significant difference in the maximal pain score between the two groups (p=0.934). Conclusions: This single-blind randomized preliminary study showed that recombinant human EGF-based cream can have a beneficial role in preventing or minimizing radiation dermatitis in breast cancer patients. To confirm the results of our study, additional studies with a large sample size are required.

Clinical Outcome of Helical Tomotherapy for Inoperable Non-Small Cell Lung Cancer: The Kyung Hee University Medical Center Experience

Kong, Moonkyoo,Hong, Seong Eon Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.4

Background: Published studies on clinical outcome of helical tomotherapy for lung cancer are limited. The purpose of this study was to evaluate clinical outcomes and treatment-related toxicity in inoperable non-small cell lung cancer (NSCLC) patients treated with helical tomotherapy in Korea. Materials and Methods: Twenty-seven patients with NSCLC were included in this retrospective study. Radiotherapy was performed using helical tomotherapy with a daily dose of 2.1-3 Gy delivered at 5 fractions per week resulting in a total dose of 62.5-69.3 Gy. We assessed radiation-related lung and esophageal toxicity, and analyzed overall survival, locoregional recurrence-free survival, distant metastasis-free survival, and prognostic factors for overall survival. Results: The median follow-up period was 28.9 months (range, 10.1-69.4). The median overall survival time was 28.9 months, and 1-, 2-, and 3-year overall survival rates were 96.2%, 92.0%, and 60.0%. The median locoregional recurrence-free survival time was 24.3 months, and 1-, 2-, and 3-year locoregional recurrence-free survival rates were 85.2%, 64.5%, and 50.3%. The median distant metastasis-free survival time was 26.7 months, and 1-, 2-, and 3-year distant metastasis-free survival rates were 92.3%, 83.9%, and 65.3%, respectively. Gross tumor volume was the most significant prognostic factor for overall survival. No grade 4 or more toxicity was observed. Conclusions: Helical tomotherapy in patients with inoperable NSCLC resulted in high survival rates with an acceptable level of toxicity, suggesting it is an effective treatment option in patients with medically inoperable NSCLC.

A Long Term Results of External Beam Radiation Therapy in Hemophilic Arthropathy of the Ankle in Children

Kong, Moonkyoo,Kang, Jin Oh,Choi, Jinhyun,Park, Seo Hyun The Korean Academy of Medical Sciences 2010 JOURNAL OF KOREAN MEDICAL SCIENCE Vol.25 No.12

<P>Bleeding into joint space is critical to develop hemophilic arthropathy. To reduce the frequency of bleeding in the ankle joint of children with hemophilic arthropathy, low dose external beam irradiation was performed for 37 patients. Among them, 35 patients followed-up for longer than 1 yr (median 87 months) were enrolled for analysis. The average number of bleedings per month was 3.6 during one year prior to radiation therapy. After radiation therapy, it was decreased to 2.1 during the first year, after then it was maintained in the range of 1.0 to 1.5 until the tenth year. The bleeding frequency was reduced to 42% at the first year and it was maintained in the range of 58% to 73% from the second to the tenth year. Especially the patients who had 3 or more bleedings per month, and who had MRI score more than 3 showed significant decreases. During the follow-up period, growth disturbances and secondary malignancies were not found. External beam radiotherapy can be considered for the hemophilic patients with surgical or isotope therapies are not amenable.</P>

Predictive Factors for Supraclavicular Lymph Node Recurrence in N1 Breast Cancer Patients

Kong, Moonkyoo,Hong, Seong Eon Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.4

Background: The purpose of this study was to identify predictive factors for supraclavicular lymph node recurrence (SCLR) in N1 breast cancer patients and define a high-risk subgroup who might benefit from supraclavicular nodal radiotherapy (RT). Materials and Methods: From January 1995 to December 2009, 113 breast cancer patients with 1 to 3 positive axillary lymph nodes were enrolled in this study. All patients underwent breast-conserving surgery (BCS) or modified radical mastectomy (MRM). RT was given to all patients who received BCS. Among the patients given MRM, those with breast tumors >5 cm in size received RT. Regional nodal irradiation was not applied. Systemic chemotherapy was given to 105 patients (92.9%). Patient data were retrospectively reviewed and analyzed to identify predictive factors for SCLR. Results: The median follow-up duration was 6.5 years, with 5- and 10-year actuarial SCLR rates of 9.3% and 11.2%, respectively. Factors associated with SCLR on univariate analysis included histologic grade, number of dissected axillary lymph nodes, lymphovascular invasion, extracapsular extension (ECE), and adjuvant chemotherapy. On multivariate analysis, histologic grade and ECE remained significant. The patient group with grade 3 and ECE had a significantly higher rate of SCLR compared with the remainder (5-year SCLR rate; 71.4% vs. 4.0%, p<0.001). Conclusions: Histologic grade and ECE status are significant predictive factors for SCLR. Supraclavicular nodal RT is necessary in N1 breast cancer patients featuring histologic grade 3 and ECE.

Comparison of survival rates between patients treated with conventional radiotherapy and helical tomotherapy for head and neck cancer

Kong, Moonkyoo,Hong, Seong Eon,Choi, Jinhyun,Kim, Youngkyong The Korean Society for Radiation Oncology 2013 Radiation Oncology Journal Vol.31 No.1

Purpose: Compared to conventional radiotherapy (RT), intensity-modulated radiotherapy (IMRT) significantly reduces the rate of treatment-induced late toxicities in head and neck cancer. However, a clear survival benefit of IMRT over conventional RT has not yet been shown. This study is among the first comparative study to compare the survival rates between conventional RT and helical tomotherapy in head and neck cancer. Materials and Methods: From January 2008 to November 2011, 37 patients received conventional RT and 30 patients received helical tomotherapy for management of head and neck cancer. We retrospectively compared the survival rates between patients treated with conventional RT and helical tomotherapy, and analyzed the prognostic factors for survival. Results: The 1- and 2-year locoregional recurrence-free survival rates were 61.2% and 58.1% for the conventional RT group, 89.3% and 80.3% for the helical tomotherapy group, respectively. The locoregional recurrence-free survival rates of the helical tomotherapy group were significantly higher than conventional RT group (p = 0.029). There were no significant differences in the overall and distant metastasis-free survival between the two groups. RT technique, tumor stage, and RT duration were significant prognostic factors for locoregional recurrence-free survival. Conclusion: This study showed the locoregional recurrence-free survival benefits of helical tomotherapy in the treatment of head and neck cancers.

Comparison of survival rates between patients treated with conventional radiotherapy and helical tomotherapy for head and neck cancer

Moonkyoo Kong,Seong Eon Hong,Jinhyun Choi,Youngkyong Kim 대한방사선종양학회 2013 Radiation Oncology Journal Vol.31 No.1

Purpose: Compared to conventional radiotherapy (RT), intensity-modulated radiotherapy (IMRT) significantly reduces the rate of treatment-induced late toxicities in head and neck cancer. However, a clear survival benefit of IMRT over conventional RT has not yet been shown. This study is among the first comparative study to compare the survival rates between conventional RT and helical tomotherapy in head and neck cancer. Materials and Methods: From January 2008 to November 2011, 37 patients received conventional RT and 30 patients received helical tomotherapy for management of head and neck cancer. We retrospectively compared the survival rates between patients treated with conventional RT and helical tomotherapy, and analyzed the prognostic factors for survival. Results: The 1- and 2-year locoregional recurrence-free survival rates were 61.2% and 58.1% for the conventional RT group, 89.3% and 80.3% for the helical tomotherapy group, respectively. The locoregional recurrence-free survival rates of the helical tomotherapy group were significantly higher than conventional RT group (p = 0.029). There were no significant differences in the overall and distant metastasis-free survival between the two groups. RT technique, tumor stage, and RT duration were significant prognostic factors for locoregional recurrence-free survival. Conclusion: This study showed the locoregional recurrence-free survival benefits of helical tomotherapy in the treatment of head and neck cancers.

Concurrent Chemoradiotherapy for Loco-regionally Advanced Nasopharyngeal Carcinoma: Treatment Outcomes and Prognostic Factors

Kong, Moonkyoo,Lim, Yu Jin,Kim, Youngkyong Asian Pacific Education Press Ltd. 2018 ASIAN PACIFIC JOURNAL OF CANCER PREVENTION Vol.19 No.6

<P><B>Background:</B></P><P>We conducted this study to contribute to resolving some controversial issues on management of nasopharyngeal carcinoma.</P><P><B>Methods:</B></P><P>Thirty-two patients with stage III-IVB nasopharyngeal carcinoma were included in this retrospective study. All patients received concurrent chemoradiotherapy with either 3D conformal radiotherapy or intensity-modulated radiotherapy. We retrospectively analyzed the survival outcome, prognostic factors for survival, and toxicity outcome.</P><P><B>Results:</B></P><P>The 2- and 5-year overall survival rates were 89.9% and 82.6%. The 2- and 5-year distant metastasis-free survival rates were 83.2% and 79.4%. The 2- and 5-year loco-regional recurrence-free survival rates were 83.3% and 79.5%. Addition of induction chemotherapy to concurrent chemoradiotherapy did not improve survival outcomes. The survival benefit of intensity-modulated radiotherapy over 3D conformal radiotherapy was not clear. Intensity-modulated radiotherapy significantly decreased the development of late toxicities compared with 3D conformal radiotherapy. Total RT dose was prognostic factor for overall, loco-regional recurrence-free, and distant metastasis-free survival. Temporary RT interruption was prognostic factor for overall survival. Daily RT dose was prognostic factor for distant metastasis-free survival.</P><P><B>Conclusions:</B></P><P>Concurrent chemoradiotherapy resulted in high survival rates with an acceptable level of toxicities in patients with loco-regionally advanced nasopharyngeal carcinoma. To confirm the results of this study, well-designed randomized prospective trials are warranted.</P>

Three Cases of Radiation-Induced Hepatitis B Virus Reactivation after Hepatic Tomotherapy

공문규(Moonkyoo Kong),홍성언(Seong Eon Hong),김병호(Byung-Ho Kim),최진현(Jinhyun Choi) 대한방사선종양학회 2011 Radiation Oncology Journal Vol.29 No.1

방사선간염은 대개 황달을 동반하지 않은 알칼리인산 분해효소(alkaline phophatase)의 상승을 특징으로 보인다. 하지만, 방사선간염 환자의 일부에서는 아미노전달효소(transaminase)의 상승을 특징적인 소견으로 보이고, 이러한 소견은 특히 간암 환자의 70∼90%가 B형 간염 바이러스 보균자인 아시아 지역에서 흔하게 관찰된다. 또한 B형 간염 바이러스 보균자인 간암 환자를 방사선으로 치료했을 때 방사선간염이 더 흔하게 발생한다. 이런 사실들은 B형 간염 바이러스 보균자에서 방사선간염의 발생 기전이 비보균자에서의 그것과 다를 수 있다는 것을 시사하고, B형 간염 바이러스 보균자에서 발생하는 방사선간염의 발생기전은 B형 간염 바이러스의 재활성화와 연관이 있을 것으로 추측된다. 하지만, 현재 간암의 방사선치료 후 B형 간염 바이러스의 재활성화에 대한 연구는 미미한 수준이다. 이에 저자들은 간암 환자의 토모테라피 후 발생한 B형 간염 바이러스 재활성화 3예를 보고하고자 한다. Radiation-induced liver disease (RILD) has been characterized as a veno-occlusive disease with anicteric elevation of alkaline phosphatase (ALP). However, some RILD patients present with elevated transaminase levels rather than with anicteric elevation of ALP, and these findings are common in the Asia-Pacific region where hepatitis B virus (HBV) infection is associated with 70∼90% of hepatocelluar carcinoma (HCC) cases. In addition, the development of RILD is more common in patients with hepatitis B virus-related HCC. These findings indicate that susceptibility to RILD might be different in HBV carriers and non-carriers, and moreover, RILD in patients with HBV-related HCC might be associated with another unique pathogenesis such as HBV reactivation. However, HBV reactivation after hepatic irradiation has been reported in only a few studies. This study reports three cases of HBV reactivation after hepatic tomotherapy for management of HCC.