• Radiation Oncology Journal
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• 제24권2호
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• pp.96-102
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• 2006

목적: 국한성병기 소세포폐암 환자에서 하루 두 번 분할조사에 의한 동시 화학방사선치료의 효율성을 치료 반응률, 생존율, 실패양상, 치료부작용 등의 관점에서 평가하기 위해 후향적 연구를 수행하였다. 대상 및 방법: 1993년 2월부터 2002년 10월까지 총 76명의 환자가 조직학적으로 증명된 국한성병기 소세포폐암으로 하루 두 번 분할조사에 의한 동시 화학방사선치료를 시행 받았다. 대상환자 중 남성은 84% (64/76)이었고, 중앙연령은 57세였다(32-75세). 흉부방사선치료는 120 또는 150 cGy/fraction로 최소 6시간의 간격을 두고 하루 두 번, 한 주에 5일 시행하였다. 총 흉부조사선량의 중앙값은 50.4 Gy였다(45-51 Gy). 동시 화학치료은 3주 간격으로 교대 CAV ($cytoxan\;1000mg/m^2,\;adriamycin\;40mg/m^2,\;vincristine\;1mg/m^2$)/PE ($cisplatin\;60mg/m^2,\;etoposide\;100mg/m^2$)이거나, 혹은 단독 PE 요법이 사용되었다. 화학치료 횟수의 중앙값은 6회였다(1-9회). 예방적 전뇌조사는 완전관해를 보인 환자에게 25 Gy/10 fractions로 시행되었다. 중앙추적관찰기간은 18개월이었다(1-136개월). 결과: 치료의 반응률은 86%이었다: 완전관해가 39명(52%), 부분관해가 26명(34%)이었다. 중앙생존기간은 23개월이었다. 1년, 2년, 3년 생존율은 각각 72%, 50%, 30%이었다. 단변량분석에서 치료 반응률이 생존율의 유의한 예후인자로 밝혀졌다(p<0.001). 등급 3 이상의 급성부작용은 백혈구감소 46명(61%), 적혈구 감소 5명 (6%), 혈소판 감소 10명(13%), 식도염 5명(6%), 그리고 폐독성이 2명(2%)에서 있었다. 추척관찰이 가능했던 73명의 환자 중 총 38명(52%)에서 병의 진행이 관찰되었다. 첫 번째 원격전이 장소의 빈도는 뇌가 가장 높았다. 결론: 하루 두 번 분할조사에 의한 동시 화학방사선치료는 국한성병기 소세포폐암 환자에서 나쁘지 않은 부작용과 함께 양호한 치료반응 및 생존율의 결과를 보였다. 생존율의 유의한 예후인자로 밝혀진 치료 반응률을 향상시키기 위해 방사선치료 분할방식, 화학요법제제, 화학방사선치료의 결합방식에 대한 추가적인 연구가 필요할 것으로 생각된다.

• Journal of Chest Surgery
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• 제38권4호
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• pp.263-270
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• 2005

최근 고령화 사회가 진행되어 가면서 폐암환자에서도 수술에 적응이 되지 않는 고령의 환자가 점차 증가하는 추세를 보이고 있어 독성이 적은 치료방법의 개발에 대한 필요성이 증가되고 있다. 따라서 기존의 항암제에 비하여 비교적 안정적으로 사용이 가능할 것으로 생각되는 선택적인 COX-2 억제제인 Nimesulide를 처치하여 COX-2 발현 유무와 COX-2 억제제가 비소세포폐암에 미치는 세포독성과의 상관관계를 연구하였다. 대상 및 방법: A549, H1299 비소세포폐암 세포주에서 COX-2 단백질에 대한 면역조직화학염 색을 시행하였으며, Nimesulide 처치후 XTT 분석, FACS 분석, Hoechst 33258 염색을 시행하였다. 결과: COX-2 단백질의 면역조직화학염색결과 A549 비소세포폐암 세포주는 COX-2 단백질에 강한 발현을 나타낸 반면, H1299 비소세포폐암 세포주는 발현을 나타내지 않았다. XTT 분석결과 Nimesulide의 A549, H1299 비소세포폐암 세포주에 대한 세포독성은 유사하였으며, Nimesulide의 $IC_{50}$은 A549 비소세포폐암 세포주에서는 $70.9 {\mu}M$이었으며, H1299 비소세포폐암 세포주에서는 $56.5 {\mu}M$이었다. FACS 분석에서는 각각의 세포군에서 $G_0/G_1$ 기에서 세포주기의 지연이 관찰되었으며, S기의 세포는 감소되었다. Hoechst 33258 염색에서는 양군에서 세포핵의 주변부 농축 현상 및 핵 분절을 가진 많은 사멸세포가 관찰되었다. 걸론: 선택적인 COX-2억제제인 Nimesulide는 비소세포폐암 세포주에서 암세포의 증식을 억제함을 알 수 있었으며, 암세포증식 억제의 기전은 세포자멸사의 유도와 $G_0/G_1$기에서 세포주기의 지연임을 알 수 있었으며, COX-2의 발현유무와 세포독성은 차이가 없는 것을 알 수 있었다. 따라서 Nimesulide와 같은 선택적인 COX-2 억제제는 다양한 항암제나 방사선치료와 병행하여 고위험군의 폐암환자에서 매우 효과적으로 사용될 수 있을 것으로 기대된다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권2호
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• pp.929-935
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• 2014

Two types of nanosized titanium dioxide, anatase ($anTiO_2$) and rutile ($rnTiO_2$), are widely used in industry, commercial products and biosystems. $TiO_2$ has been evaluated as a Group 2B carcinogen. Previous reports indicated that $anTiO_2$ is less toxic than $rnTiO_2$, however, under ultraviolet irradiation $anTiO_2$ is more toxic than $rnTiO_2$ in vitro because of differences in their crystal structures. In the present study, we compared the in vivo and in vitro toxic effects induced by $anTiO_2$ and $rnTiO_2$. Female SD rats were treated with $500{\mu}g/ml$ of $anTiO_2$ or $rnTiO_2$ suspensions by intra-pulmonary spraying 8 times over a two week period. In the lung, treatment with $anTiO_2$ or $rnTiO_2$ increased alveolar macrophage numbers and levels of 8-hydroxydeoxyguanosine (8-OHdG); these increases tended to be lower in the $anTiO_2$ treated group compared to the $rnTiO_2$ treated group. Expression of $MIP1{\alpha}$ mRNA and protein in lung tissues treated with $anTiO_2$ and $rnTiO_2$ was also significantly up-regulated, with $MIP1{\alpha}$ mRNA and protein expression significantly lower in the $anTiO_2$ group than in the $rnTiO_2$ group. In cell culture of primary alveolar macrophages (PAM) treated with $anTiO_2$ and $rnTiO_2$, expression of $MIP1{\alpha}$ mRNA in the PAM and protein in the culture media was significantly higher than in control cultures. Similarly to the in vivo results, $MIP1{\alpha}$ mRNA and protein expression was significantly lower in the $anTiO_2$ treated cultures compared to the $rnTiO_2$ treated cultures. Furthermore, conditioned cell culture media from PAM cultures treated with $anTiO_2$ had less effect on A549 cell proliferation compared to conditioned media from cultures treated with $rnTiO_2$. However, no significant difference was found in the toxicological effects on cell viability of ultra violet irradiated $anTiO_2$ and $rnTiO_2$. In conclusion, our results indicate that $anTiO_2$ is less potent in induction of alveolar macrophage infiltration, 8-OHdG and $MIP1{\alpha}$ expression in the lung, and growth stimulation of A549 cells in vitro than $rnTiO_2$.

• Tuberculosis and Respiratory Diseases
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• 제53권3호
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• pp.275-284
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• 2002

연구배경: Gemcitabine은 폐암에서 임상적 유용성이 큰 새로운 항암제이다. 저자들은 폐암세포에서 Gemcita bine에 의한 세포 사멸과 p53의 역할을 규명하고자 하였다. 방 법 : 폐암 세포주로 A549와 H358 세포주를 이용하였고 세포 독성 검사는 MTT assay를 이용하였으며 Gemcitabine 농도는 10nM, 100nM, 1uM, 10uM, 100uM을 사용하였다. 세포 주기 검사는 FACScan을 이용하여 분석하였고 p53 활성화 여부는 western blot을 사용하였다. p53 단백질 분해를 촉진시키는 안정적 세포주 A549-E6과 H358-E6을 제조하고 대조 세포주 A549-neo와 H358-neo 세포주와 비교하여 p53의 기능적 knock-out 실험을 시행하였다. p53의 기능적 knock-out은 p53 유도 약제인 doxorubicine 1 M을 사용하여 western blot으로 확인하였다. 결 과 : A549와 H358 세포주에서 Gemcitabine은 농도에 비례한 세포 독성을 보였고 S phase arrest와 p53의 활성화를 유도하였다. 안정적 세포주 A549-E6과 H358-E6은 MTT assay에서 대조 세포주 A549-noo와 H358-noo에 비해 각각 20-30%, 30-40%의 세포 독성 차단효과를 보였다. 결 론 : Gemcitabine은 S phase arrest를 유발시키고 p53 단백질의 활성화를 유도하며 p53의 기능소실이 Gemcitabine에 대한 저항인자로 작용하고 있음을 확인할 수 있었다. 향후 Gemcitabine에 의해 p53의 활성화가 발생하는 신호경로와 p53 활성화에 의한 아포프토시스의 신호경로에 대한 연구가 필요할 것으로 사료된다.

• Journal of Hospice and Palliative Care
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• 제19권1호
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• pp.70-75
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• 2016

완치가 불가능한 진행성 암환자에게 시행되는 완화적 항암치료의 목표는 생명연장과 삶의 질 향상이다. 그러나 완화적 항암치료는 상당한 독성을 가질 수도 있기 때문에 의사는 항암제 투여의 중단시점에 대해, 특히 생의 마지막 몇 달 내 기간에는, 항상 지속적으로 평가해야 한다. 완화적 항암치료를 중단하는 분명한 권고안은 없지만 진행성 암환자 돌봄의 질 향상을 위해 해결해야 할 쟁점이다. 저자는 완화적 항암치료를 투여 받았던 진행성 대장암, 비소세포 폐암 환자 두 증례를 기술하였다. 두 증례 모두 완화적 항암치료의 중단에 대한 공동 결정 하에 현재까지 최대한의 증상 치료를 시행하고 있다. 두 증례와 최근까지의 문헌고찰을 통해 국내 호스피스 완화의료가 확립 되어가는 시점에서, 항암치료의 중단 시점과 결정에 대해 부각시키는 바이다.

• 대한약침학회지
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• 제19권4호
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• pp.303-311
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• 2016

Objectives: Allergic asthma generally presents with symptoms of wheezing, coughing, breathlessness, and airway inflammation. Seonpyejeongcheon-tang (SJT) consists of 12 herbs. It originated from Jeong-cheon-tang (JT), also known as Ding-chuan-tang, composed of 7 herbs, in She-sheng-zhong-miao-fang. This study aimed to evaluate the effects of local delivery of SJT via inhalable microparticles in an asthma mouse model. Methods: Microparticles containing SJT were produced by spray-drying with leucine as an excipient. SJT microparticles were evaluated with respect to their aerodynamic properties, in vitro cytotoxicity, in vivo toxicity, and therapeutic effects on ovalbumin (OVA)-induced asthma in comparison with orally-administered SJT. Results: SJT microparticles provided desirable aerodynamic properties (fine particle fraction of $48.9%{\pm}6.4%$ and mass median aerodynamic diameter of $3.7{\pm}0.3{\mu}m$). SJT microparticles did not show any cytotoxicity against RAW 264.7 macrophages at concentrations of 0.01 - 3 mg/mL. Inhaled SJT microparticles decreased the levels of IL-4, IL-5, IL-13, IL-17A, eotaxin and OVA-IgE in bronchoalveolar lavage fluid (BALF) in mice with OVA-induced asthma. These effects were verified by histological evaluation of the levels of infiltration of inflammatory cells and collagen, destructions of alveoli and bronchioles, and hyperplasia of goblet cells in lung tissues. The effects of SJT microparticles in the asthma model were equivalent to those of orally-administered SJT extract. Conclusion: This study suggests that SJT is a promising agent for inhalation therapy for patients with asthma.

• Journal of Pharmaceutical Investigation
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• 제33권4호
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• pp.287-292
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• 2003

A novel antitumor agent, antibody-endostatin fusion protein $(anti-HER2/neu\;IgG3C_H3-Endostatin,\;AEFP)$ formed by genetic engineering procedure from antibody (Ab) which specifically targets to tumor cells ad angiogenesis inhibitor, endostatin (Endo) that has excellent antitumor effect, minimizes the toxicity of normal cells and selectively kills only tumor cells. The purpose of this study is to evaluate the phamacokinetic parameters and to analyze the localization of AEFP. After an intravenous injection of $150\;{\mu}l\;(5\;{\mu}Ci)\;[^{125}I]Ab,\;[^{125}I]AEFP$ to mice, blood was collected though retroorbital plexus from 15 min to 2880 min. Following the jugular vein injetion of $150\;{\mu}l\;(10\;{\mu}Ci)\;[^{125}I]Endo$, blood was collected by the use of carotid artery cannulation from 0.25 min to 30 min. Consequently, Endo was very rapidly removed from plasma compartment within 30 min. On the other hand, AEFP similar to Ab was slowly cleared from plasma. Also, Endo was metabolized about 40% within 30 min. However, AEFP was shown to metabolize less than 10% within 2880 min. The organ distribution of Endo was in order kidney, lung, spleen. Both Ab and AEFP were localized in order spleen, kidney, liver. Futhermore the tumor/blood distribution ratio of AEFP at 96 hours after injection is about 20 times higher than it of Endo at one hour after injection. In conclusion, these studies demonstrate that the anti-cancer or suppression of angiogenesis effect of Endo may be improved by the use of AEFP because the longer half life and stability of AEFP is able to selectively target antigens expressed on tumors.

• Journal of Korean Neurosurgical Society
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• 제58권3호
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• pp.217-224
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• 2015

Objective : To investigate the efficacy and safety of fractionated stereotactic radiosurgery for large brain metastases (BMs). Methods : Between June 2011 and December 2013, a total of 38 large BMs >3.0 cm in 37 patients were treated with fractionated Cyberknife radiosurgery. These patients comprised 16 men (43.2%) and 21 women, with a median age of 60 years (range, 38-75 years). BMs originated from the lung (n=19, 51.4%), the gastrointestinal tract (n=10, 27.0%), the breast (n=5, 13.5%), and other tissues (n=3, 8.1%). The median tumor volume was 17.6 cc (range, 9.4-49.6 cc). For Cyberknife treatment, a median peripheral dose of 35 Gy (range, 30-41 Gy) was delivered in 3 to 5 fractions. Results : With a median follow-up of 10 months (range, 1-37 months), the crude local tumor control (LTC) rate was 86.8% and the estimated LTC rates at 12 and 24 months were 87.0% and 65.2%, respectively. The median overall survival (OS) and progression-free survival (PFS) rates were 16 and 11 months, respectively. The estimated OS and PFS rates at 6, 12, and 18 months were 81.1% and 65.5%, 56.8% and 44.9%, and 40.7% and 25.7%, respectively. Patient performance status and preoperative focal neurologic deficits improved in 20 of 35 (57.1%) and 12 of 17 patients (70.6%), respectively. Radiation necrosis with a toxicity grade of 2 or 3 occurred in 6 lesions (15.8%). Conclusion : These results suggest a promising role of fractionated stereotactic radiosurgery in treating large BMs in terms of both efficacy and safety.

• Journal of Korean Neurosurgical Society
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• 제61권4호
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• pp.525-529
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• 2018

Objective : To evaluate the efficacy of fractionated stereotactic radiosurgery (FSRS) performed using the Novalis $Tx^{(R)}$ system (BrainLAB AG, Feldkirchen, Germany; Varian Medical Systems, Palo Alto, CA, USA) for brain metastases. Methods : Between March 2013 and July 2016, 23 brain metastases patients were admitted at a single institute. Twenty-nine lesions too large for single session stereotactic radiosurgery or located in the vicinity of eloquent structures were treated by FSRS. Based on the results obtained, we reviewed the efficacy and toxicity of FSRS for the treatment of brain metastases. Results : The most common lesion origin was lung (55%) followed by breast (21%). Median overall survival was 10.0 months (95% confidence interval [CI], 4.9-15.0), and median progression-free survival was 10.0 months (95% CI, 2.1-13.9). Overall survival rates at 1 and 2 years were 58.6% and 36.0%, respectively. Local recurrence and neurological complications affecting morbidity each occurred in two cases. Conclusion : FSRS using the $Novalis-Tx^{(R)}$ system would appear to be an effective, safe noninvasive treatment modality for large and eloquently situated brain metastases. Further investigation is required on a larger number of patients.

• Environmental Analysis Health and Toxicology
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• 제20권2호
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• pp.179-186
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• 2005

Particulate materials (PM) less than 10 ${\mu}m$ in diameter are of special interest in air pollution because they are respirable and responsible for the increasing mortality rate of lung cancer and cardiovascular diseases. These particles are often referred to as $PM_{10}$ and they are divided into a coarse fraction and a fine fraction which is also often referred to as $PM_{25}$. In this study, we monitored the TSP, $PM_{10},\;PM_{2.5}$ concentration of ambient air collected in northern part of Seoul in early spring and measured the concentration of heavy metals; Cr, Mn, Zn, As, Cd, and Pb. All the heavy metals were found in the collected particles and the concentrations were variable in the $PM_{10},\;and\;PM_{2.5}$ respectively. The detected concentration ranges were Cr: $ND\~2,889ng/m^3,\;Mn:2.4\~257.9ng/m^3,\;Zn:ND\~353.7ng/m^3,\; As:ND\~22.3ng/m^3,\;Cd:0.1\~2.9ng/m^3,\;and\;Pb:ND\~392.2ng/m^3$ in fine particles. Heavy metal toxicity of the particles were also tested in $H_9C_2$ cell line derived from rat cardiomyocytes. As for the results of health risk assessment calculated by unit risk of IRIS, heavy metals in ambient air of Seoul metropolitan area were found to be responsible for the increase of total excess cancer risk. Among them, chromium (hexavalent) was found to be the most risky in fine particles of ambient air collected in the northern part of Seoul in early spring.