• 대한본초학회지
• /
• 제30권1호
• /
• pp.33-42
• /
• 2015

Objectives : The aim of this study was to evaluate the antitumor effects of Cheongpyesagan-tang(CST) and YKK012 on colon cancer. Methods : MTT assay was used to evaluate the cytotoxicity of Single herbs and combinations of CST and YKK012 on murine colon cancer cells, Colon 38. To explain effects of apoptosis in colon cancer, we performed the western blot. Effects of CST and YKK012 on antitumor activity of CPT-11 using the murine colon38 allograft tumor in BDF1 mice. Results : Single herbs and combinations of CST and YKK012 was tested in vitro, Rhei Radix (RH) and Scutellariae Radix (SC) and YKK012 showed dose-response cytotoxicity on Colon 38. This might be due to the apoptosis, as we see Bax and Caspase-3, which are apoptotic factors, was expressed in RH and SC treated cells. YKK012 also showed increased expression of Caspase-3. In mouse colorectal cancer xenograft model of colon38 cells, herbal combinations showed tendencies of tumor regression, but was not significant. Furthermore, because toxicity was observed in CST group, we reduced the dose of CST for the next experiment. The anti-tumor effects of herbal combinations were insufficient to be used as single anti-tumor agent. With simultaneous usage of CPT-11, contrary to that CST showed no synergistic effects, YKK012 which was composed by the combination of four $ER{\beta}$ selective herbs, significantly reduced the size of tumor and Bax expression was increased. Conclusions : We suggest YKK012 can be a effective cancer adjuvant therapy with CPT-11 on colon cancer.

• 대한수의학회지
• /
• 제34권1호
• /
• pp.165-172
• /
• 1994

DA-125는 새로운 안트라사이클린계 항암성 항생제로서 아드리아마이신의 유도체이다. Sprague-Dawley 랫트를 이용하여 DA-125의 배아 및 태자독성발현능력을 조사하였다. 교미확인(정충확인일=0일)된 120마리의 랫트를 4개군으로 나눈후 0, 0.1, 0.3 및 1.0mg/kg의 용량으로 임신 7일 부터 임신 17일까지 1일 1회 연속 정맥투여 하였으며 임신 20일째에 제왕절개를 하여 태자를 적출하였다. 1mg/kg 투여군에서는 모동물의 사료섭취량의 감소, 체중감소 및 비장중량의 감소와 배아 흡수율의 증가 및 태자체중의 감소가 관찰되었다. 또한 여러가지 종류의 외표, 내부장기 및 골격기형들이 각각 11.9, 41.8 및 14.5%의 빈도로 출현했다. 그중 특이 기형소견으로는 뇌탈출증, 복벽파열, 외측 및 제3뇌실의 확장, 늑골유착 등을 들 수 있다. 0.1 및 0.3mg/kg 투여군에서는 어떠한 배아 및 태자 독성증상도 나타나지 않았다. 이상의 결과에서 DA-125는 랫트에 있어서 경미한 모독성 용량에서 배아 및 태자독성효과를 나타냄을 알 수 있었다.

• 대한한방종양학회지
• /
• 제8권1호
• /
• pp.103-125
• /
• 2002

This experimental study was carried out to evaluate the anti-tumor and the immunomodulatory effects of Jiaweicitaowan(加未慈桃丸) against cancer. The in vitro anti-tumor effects were evaluated by MTT assay. The cytotoxicity, extension of survival days, the effect of inhibition solid tumor which was induced sarcoma 180, and the changes of body weight were evaluated for in vivo effects of anti-tumor. To evaluate the immunomodulatory effects of Jiawei- citaowan(加未慈桃丸), delayed type hypersensitivity, hemagglutinin, hemolysin titers for humoral immune response, rosette forming cells for cell-mediated immune response, natural killer cell activity, proliferation of lymphocyte, productivty of Interleukin-2, and carbon clearance were measured with methotrexate treated mice. The results were as follows; 1. In the case of existence ability of tumor cell, IC50 had an anti-tumor ativity resulted 2.52mg/ml to SNU-C4. 0.41mg/ml to SNU-396, resulted to 0.09mg/mlSNU-1. 2. The groups of Jiaweicitaowan(加未慈桃丸) 10mg/ml, 20mg/kg had no body weight loss. reduction in intake of water and feed, so these had no toxicity. 3. In the case of the effect of extention of existence. the group of 20mg/kg Jiaweicitaowan(加未慈桃丸) extract treated group was showed 250% in ILS. 4. The effect of inhibition solid tumor was significantly decreased in both 10mg/kg, 20mg/kg of Jiaweicitaowan(加未慈桃丸) extract treated groups as compared with control group S. The groups of 10mg/kg, 20mg/kg Jiaweicitaowan(加未慈桃丸) had significant effect of body weight change compared to control group. 6. Delayed type hypersensitivity was not significant in both Jiaweicitaowan(加未慈桃丸) extract treated groups as compared with control group. 7. Hemagglutinin and Hemolysin titers were significantly increased by dose-dependent. so these results showed that the humoral immume respose was activated. 8. For the effect of rosette formimg cells was not significant in hoth Jiaweicitaowan(加未慈桃丸) extract treated groups as compared with control group. 9. Natural killer cell activity was significantly increased in both Jiaweicitaowan(加未慈桃丸) extract treated groups as compared with control group in the ratio of 100: 1, 50: 1 of effector and target cells, but in the ratio of 10:1, the Jiaweicitaowan(加未慈桃丸) extract treated groups were not significant. 10. The proliferation of lymphocyte and productivty of Interleukin-2 were significantly increased by dose-dependent in both 10mg/ kg, 20mg/ kg of Jiaweicitaowan(加未慈桃丸) extract treated groups as compared with control group. 11. In the phagocytic effect, the 20mg/kg of Jiaweicitaowan(加未慈桃丸) extract treated group showed the increasing effect with significance as compared with control group. According to the results, we can suggest that Jiaweicitaowan(加未慈桃丸) has the antitumor and the immunomodulatory effects.

• Radiation Oncology Journal
• /
• 제38권2호
• /
• pp.109-118
• /
• 2020

Purpose: Hypofractionated radiotherapy (RT) is becoming a new standard in postoperative treatment of patients with early stage breast cancer after breast conservation surgery. However, data on hypofractionation in patients with advanced stage disease who undergo mastectomy followed by local and regional nodal irradiation (RNI) is lacking. In this retrospective study, we report late-term effects of 3 weeks post-mastectomy hypofractionated local and RNI with two-dimensional (2D) technique in patients with stage II and III breast cancer. Methods: Between January 1990 and December 2007, 1,770 women with breast cancer who were given radical treatment with mastectomy, systemic therapy and RT at least 10 years ago were included. RT dose was 35 Gy/15 fractions/3 weeks to chest wall by two tangential fields and 40 Gy in same fractions to supraclavicular fossa (SCF) and internal mammary nodes (IMNs). SCF and IMNs dose was prescribed at d_max and 3 cm depth, respectively. Chemotherapy and hormonal therapy was given in 64% and 74% patients, respectively. Late-term toxicities were assessed with the Radiation Therapy Oncology Group (RTOG) scores and LENT-SOMA scales (the Late Effects Normal Tissue Task Force-Subjective, Objective, Management, Analytic scales). Results: Mean age was 48 years (range, 19 to 75 years). Median follow-up was 12 years (range, 10 to 27 years). Moderate/marked arm/shoulder pain was reported by 254 (14.3%) patients. Moderate/marked shoulder stiffness was reported by 219 (12.3%) patients. Moderate/marked arm edema was seen in 131 (7.4%) patients. Brachial plexopathy was not seen in any patient. Rib fractures were noted in 6 (0.3%) patients. Late cardiac and lung toxicity was seen in 29 (1.6%) and 23 (1.3%) patients, respectively. Second malignancy developed in 105 (5.9%) patients. Conclusion: RNI with 40 Gy/15 fractions/3 weeks hypofractionation with 2D technique seems safe and comparable to historical data of conventional fractionation (ClinicalTrial.gov Registration No. NCT04175821).

• Radiation Oncology Journal
• /
• 제13권3호
• /
• pp.233-241
• /
• 1995

Purpose : To analyse clinical outcome and prognostic factors according to treatment modality, this paper report our experience of retrospective study of patients with esophageal cancer Materials and Methods : One hundred and ten patients with primary esophageal cancer who were treated in Presbyterian Medical Center from May 1985 to December 1992. We analysed these patients retrospectively with median follow up time of 28 months, one hundred and four patients($95{\%}$) were followed up from 15 to 69 months. In methods, twenty-eight patients were treated with median radiation dose irradiated 54.3Gy only. Fifty-six patients were treated with combined chemoradiotherapy. Sixteen cases of these patients were treated with concurrent chemoradiation and the other patients(forty cases) were treated sequential chemoradiotherapy. In concurrent chemoradiotherapy group, patients received 5-FU continuous IV infusion for 4 days. Cisplatin IV bolus. and concurrent esophageal irradiation to 30 Gy. After that patients received 5-FU continuous IV, Cisplatin bolus injection and Mitomycin-C bolus IV, Bleomycin continuous IV, and irradiation to 20 Gy. In sequential chemoradiotherapy group, the chemotherapy consisted of 5-FU 1,000mg/$m^2$ administered as a continuous 24 hour intravenous infusion during five days and Cisplatin 80-100mg/$m^2$ bolus injected, or Bleomycin, Vinblastine, Cisplatin, Methotrexate were used of 1 or 2 cycles. After preoperative concurrentm chemoradiation twenty-six patients underwent radical esophagectomy. Results : Ninety-three patients could be examined for response assessment, By treatment modality, response rates were $85.1{\%}$ for radiation alone group and $86.3{\%}$ for combined chemoradiation group. But in operation group, after one cycle of concurrent chemoradiation treatment, response rate was $61.9{\%}$. The pathologic complete response were $15.4{\%}$ in operation group. Overall median survival was II months and actuarial 5-year survival rate was $8{\%}$. The median survival interval was 6 months for radiation alone group, 11 months for combined chemoradiation group and 19 months for operation group. And also median survival was 19 months for complete responder group that 8 months for noncomplete responder group. In univariative analysis, statistically significant prognostic factors were tumor size, clinical stage, tumor response, and operation. In multivariative analysis, significantly better survival was associated with clinical stage, tumor response, radiation dose, and operation. Conclusion : Compared with radiotherapy alone, combined multimodality may improve the median survival in patients with localized carcinoma of the esophagus and toxicity is acceptable.

• Journal of Ginseng Research
• /
• 제45권1호
• /
• pp.126-133
• /
• 2021

Background: 20(S)-protopanaxadiol (20(S)-PPD), one of the aglycone derivatives of major ginsenosides, has been shown to have an anticancer activity toward a variety of cancers. This study was initiated with an attempt to evaluate its anti-cancer activity toward human endometrial cancer by cell and xenograft mouse models. Methods: Human endometrial cancer (HEC)-1A cells were incubated with different 20(S)-PPD concentrations. 20(S)-PPD cytotoxicity was evaluated using MTT assay. Apoptosis was detected using the annexin V binding assay and cell cycle analysis. Cleaved poly (ADP-ribose) polymerase (PARP) and activated caspase-9 were assessed using western blotting. HEC-1A cell tumor xenografts in athymic mice were generated by inoculating HEC-1A cells into the flank of BALB/c female mice and explored to validate 20(S)-PPD anti-endometrial cancer toxicity. Results: 20(S)-PPD inhibited HEC-1A cell proliferation in a dose-dependent manner with an IC50 value of 3.5 μM at 24 h. HEC-1A cells morphologically changed after 20(S)-PPD treatment, bearing resemblance to Taxol-treated cells. Annexin V-positive cell percentages were 0%, 10.8%, and 58.1% in HEC-1A cells when treated with 0, 2.5, and 5 μM of 20(S)-PPD, respectively, for 24 h. 20(S)-PPD subcutaneously injected into the HEC-1A cell xenograft-bearing mice three times a week for 17 days manifested tumor growth inhibition by as much as 18% at a dose of 80 mg/kg, which sharply contrasted to controls that showed an approximately 2.4-fold tumor volume increase. These events paralleled caspase-9 activation and PARP cleavage. Conclusion: 20(S)-PPD inhibits endometrial cancer cell proliferation by inducing cell death via a caspase-mediated apoptosis pathway. Therefore, the 20(S)-PPD-like ginsenosides are endowed with ample structural information that could be utilized to develop other ginsenoside-based anticancer agents.

• 생명과학회지
• /
• 제32권12호
• /
• pp.938-946
• /
• 2022

본 연구는 대풍자 에탄올 추출물에 대한 항산화 활성 및 주름생성 억제 활성을 확인하고자 하였다. 대풍자 에탄올 추출물의 항산화 활성을 확인하기 위하여 DPPH와 ABTS⁺ radical 소거능을 측정하였고 그 결과 추출물 1,000 ㎍/ml 농도에서 각각 73.5%와 74.4%의 높은 소거능을 나타냈다. 주름생성 억제 활성을 확인하기 위하여 collagenase 저해 활성을 실험하였으며, 그 결과 추출물 1,000 ㎍/ml 농도에서 78.8%의 유의할만한 우수한 결과를 보였다. 또한 추출물에 대한 세포의 독성을 확인하기 위해 MTT assay를 수행하였으며, 50 ㎍/ml 이하의 농도에서 약 91.7%의 생존율을 보여, 이후의 세포 실험은 50 ㎍/ml 이하의 농도에서 진행하였다. 섬유아세포인 CCD-986sk에 UVB (20 mJ/cm²)의 자극을 주고 대풍자 에탄올 추출물을 농도별로 처치한 후 procollagen type I과 MMP-1의 발현에 대한 영향을 확인하고자 ELISA 및 RT-PCR 분석을 하였다. 그 결과 대풍자 에탄올 추출물은 PIP의 생합성과 mRNA 발현은 농도의존적으로 증가하였으며, 특히 UVB만 자극한 Cont (각각의 생합성율은 50.3%와 45.8%)과 비교하였을 때 50 ㎍/ml의 농도에서 각각 약 64.2%와 83.4%의 생합성을 보였다. MMP-1의 protein과 mRNA 발현에 대한 결과는 농도의존적으로 감소했음을 확인하였으며, 50 ㎍/ml의 농도에서 각각 약 48.7%와 35.9%의 낮은 발현율을 보였다. 이와 같은 결과를 바탕으로 본 연구는 대풍자 에탄올 추출물이 주름억제 기능성 소재로써의 활용 가능성을 제시해 줄 것으로 사료된다.

• 대한방사성의약품학회지
• /
• 제8권2호
• /
• pp.53-61
• /
• 2022

This study aimed to increase the targeting ability against PSMA in cell therapy using metabolic glycoengineering and biorthogonal chemistry and to visualize cell trafficking using PET imaging. Cellular membranes of THP-1 cells were decorated with azide(-N₃) using Ac₄ManNAz by metabolic glycoengineering. Engineered THP-1 cells were conjugated with DBCO-bearing fluorophore (ADIBO-Cy5.5) for 1 h at different concentrations and analyzed by confocal fluorescence microscopy and flow cytometry. For PSAM ligand conjugation to THP-1 cells, Ac₄ManNAz treated THP-1 cells were incubated with DBCO-PSMA ligand (ADIBO-GUL) at a final concentration with 100 µM for 1 h. To evaluate the effect on cell recognition, PSMA ligand conjugated THP-1 cells(as effectors) were co-cultured with PSMA positive 22RV1 (as target cells) at 3 : 1 a effector-to-target cell (E/T) ratio. The interaction between THP-1 and 22RV1 was monitored by confocal fluorescence microscopy. For preparing the radiolabeled THP-1, the cells were treated at the activity of ~ 740 kBq of [⁸⁹Zr]Zr(oxinate)₄/5 × 10⁶ cells. Radiolabeled cells were analyzed for determination of cell-associated radioactivity by gamma counting and viability using MTS assay. In the cytotoxicity assay, THP-1 cells did not have any cytotoxicity even when the Ac₄ManNAz concentration was 100 µM. In confocal microscopy and flow cytometry, THP-1 cells were efficiently labeled ADIBO-Cy5.5 in a dose-dependent manner, and the dose of 100 µM was the optimal concentration for the following experiments. The clusters of PSMA ligand-conjugated THP-1 cells and 22RV1 cells were identified, indicating cell-cell recognition over the cell surface between two types of cells. Cell radiolabeling efficiency was 54.5 ± 17.8%. THP-1 labeled with 0.09 ± 0.03 Bq/cell showed no significant cytotoxicity compared to unlabeled THP-1 up to 7 days. We successfully demonstrated that Ac₄ManNAz treated cells were efficiently conjugated with ADIBO-GUL for preparing the PSMA-targeting cells, and [⁸⁹Zr]Zr(oxinate)₄ could be used to label cells without toxicity. It suggested that PSMA-ligand conjugated cell therapy could be improved cell targeting and be monitored by PET imaging.

• Radiation Oncology Journal
• /
• 제27권2호
• /
• pp.55-63
• /
• 2009

목 적: 근치적 치료가 힘든 두경부 진행암 환자들을 대상으로 시행된 소분할 방사선조사의 치료반응 정도를 객관적으로 평가해 보고, 이런 환자들에 대한 적절한 방사선치료 방법을 알아보고자 이 연구를 진행하였다. 대상 및 방법: 두경부에서 발생한 상피세포암종으로 진단되어 1998년부터 2008년까지 원발 병변 또는 림프절 병변에 대해 3 Gy 분할선량으로 고식적 소분할 방사선치료를 받았던 환자 31명을 대상으로 후향적 분석을 하였다. 대상 환자들의 방사선치료 전 컴퓨터단층촬영 영상자료를 통해 종양의 용적을 측정하였고, 이를 방사선치료 종료 후 2~3개월째의 컴퓨터단층촬영 자료와 비교하여 치료반응을 평가하였다. 아울러 소분할 방사선치료로 인한 치료독성의 빈도와 정도를 확인하였고, 전체 생존율 및 무진행 생존율, 그리고 생존율이나 치료반응과 관련된 예후인자들 알아보고자 통계 분석 작업을 하였다. 결 과: 대상 환자들의 평균 연령은 70세였으며, 85%의 경우가 stage 4였다. 종양의 용적은 평균 128.4 cc였고, ECOG 활동점수 상 1점과 2점이 67.7%였다. 총방사선량은 24~45 Gy (중간값 36 Gy)로 2명을 제외한 대부분의 환자가 30 Gy 이상 조사받았으며, 치료기간은 10~25일이었다. 완전반응을 보인 경우가 4명(12.9%)이었고, 19명(61.3%)의 환자에서 부분반응을 보였다. 중간 생존기간은 8.9개월이었으며, 1년 무진행생존율은 12.9%였다. 치료반응 정도에 따른 생존율의 차이를 발견할 수 있었으며, 원발 부위, 병기, 종양의 용적, 방사선치료 범위, 총방사선량 등이 생존율이나 치료반응 정도와 유의한 관련이 있었다. 치료 기간 및 치료 종결 후 grade 4 이상의 치료독성은 없었다. 결 론: 소분할 방사선치료 결과 약 74%의 환자들에서 종양이 줄어드는 것을 객관적으로 확인할 수 있었다. 적절한 분할선량 및 추가 방사선치료가 필요한 환자들의 선별에 있어서는 추가적인 연구가 필요하겠다.

• Radiation Oncology Journal
• /
• 제20권4호
• /
• pp.328-333
• /
• 2002

목적 : 절제 불가능한 췌장암은 예후가 불량하여 효과적인 치료법의 개발이 요망되고 있다. 본 연구에서는 Gemcitabine 또는 Paclitaxel과 5-Fluorouracil (5-FU)을 이용한 동시항암화학방사선요법을 시행하여 치료효과를 분석하고자 하였다. 대상 및 방법: 임상적으로 혹은 개복수술 소견 상 절제 불가능한 췌장암으로 진단받은 환자를 대상으로 Gemcitabine 또는 Paclitaxel과 5-FU을 이용한 동시항암화학방사선요법을 시행하였다. 방사선 치료는 원발병소와 주위 림프절을 포함하여 5주 동안 45 Gy를 조사하였다. 이 기간동안 Gemcitabine $1,000\;mg/m^2$ 또는 Paclitaxel $50\;mg/m^2$의 매주 1회 주사 및 5-FU의 매일 경구 투여를 시행하였다. 추적관찰기간은 6개월에서 36개월이었으며, 생존율은 Kaplan-Meier법을 이용하여 분석하였다. 결과 : 1999년 1월부터 2001년 11월까지 본 치료법이 시행된 경우는 54예였으며, 이중 계획된 치료를 종료한 42예를 분석하였다. 남녀 비는 30 : 12였고 중앙 연령은 60세였다. 총 54예 중 치료 중 원격전이나 암종증(carcinomatosis) 등으로의 진행 6명$(50\%)$, 시작시 불량한 전신수행 상태 4명$(33.3\%)$, 병변과 무관한 병발질환 1명$(8.3\%)$, 치료 거부 1명$(8.3\%)$ 등으로 총 12예에서 치료가 중단되었다. 42명의 환자 중 40예에서 반응 평가가 가능하였으며 완전 관해 1예, 부분 관해 24예로 관해율은 $59\%$로 나타났다. 중앙 생존값은 12개월, 1년 생존율은 $46.7\%$, 2년 생존율은 $17.0\%$였다. Grade III 이상의 치료독성으로는 혈액학적 독성이 8예$(19\%)$, 오심, 구토 등의 비혈액학적 독성이 9예$(20\%)$이었다. 이중 2명은 치료독성에 의한 상부 소화기 출혈로 사망하였다. 결론 : 절제 불가능한 췌장암에서 Gemcitabine 또는 Paclitaxel를 이용한 동시항암화학방사선요법은 관해율과 생존율에 있어서 효과적인 치료로 생각된다. 그러나 독성감소를 위한 연구가 또한 병행되어야 할 것으로 생각된다.