• BMB Reports
• /
• 제46권6호
• /
• pp.328-333
• /
• 2013

Many bioactive molecules like recombinant human bone morphogenetic protein 2 (rhBMP-2) have been developed for mineralized bone grafts, for which proper scaffolds are necessary to successfully apply the bioactive molecules. In this study, we tested the osteogenic efficacy of rhBMP-2 produced in-house in combination with gelatin sponge as the scaffold carrier in a rabbit radial defect model. The efficacy of the rhBMP-2 was determined by alkaline phosphatase activity assay of C2C12 cells. Two groups of ten rabbits each were treated with rhBMP-2/gelatin sponge, or gelatin sponge only. At 4 weeks, rhBMP-2/gelatin sponge grafts showed more bone regeneration than gelatin sponge grafts, as determined by X-ray radiography, micro-computed tomography, and histological analyses. At 8 weeks, rhBMP-2/gelatin sponge grafts exerted much stronger osteogenic effects. The study demonstrates the improved osteogenic efficacy of the rhBMP-2/gelatin sponge grafts in a rabbit radial bone defect model acting as a bone-inductive material.

• IMMUNE NETWORK
• /
• 제6권3호
• /
• pp.154-162
• /
• 2006

Background: Dendritic cell (DC)-based cancer immunotherapy is studied for several years. However, it is mainly derived from autologous PBMC or leukapheresis from patient, which has limitations about yield and ability of DC production according to individual status. In order to solve these problems, inquiries about allogeneic DCs are performed but there are no preclinical trial answers for effect or toxicity of allogeneic DC to use for clinical trial. In this study, we compared the anti-tumor effect of allogeneic and autologous DCs from mouse bone marrow stem cells in mouse metastatic melanoma model. Methods: B16F10 melanoma cells ($5{\times}10^4$/mouse) were injected intravenously into the C57BL/6 mouse. Therapeutic DCs were differentiated from autologous (C57BL/6: CDC) or allogeneic (B6C3F1: BDC) bone marrow stem cells with GM-CSF, SCF and IL-4 for 13days and pulsed with B16F10 tumor cell lysate (Blys) for 18hrs. DC intra-peritoneal injections began on the 8th day after the tumor cell injection by twice with one week interval. Results: Anti-tumor response was observed by DC treatment without any toxicity especially in allogeneic DC treated mice (tumor burden score: $2.667{\pm}0.184,\;2.500{\pm}0.463,\;2.000{\pm}0.286,\;1.500{\pm}0.286,\;1.667 {\pm}0.297$ for saline, CDC/unpulsed-DC: U-DC, CDC/Blys-DC, BDC/U-DC and BDC/Blys-DC, respectively). IFN-${\gamma}$ secretion was significantly increased in allogeneic DC group stimulated with B16F10 cell lysate ($2,643.3{\pm}5,89.7,\;8,561.5{\pm}2,204.9.\;6,901.2{\pm}141.1pg/1{\times}10^6$ cells for saline, BDC/U-DC and BDC/Blys-DC, respectively) with increased NK cell activity. Conclusion: Conclusively, promising data was obtained that allogeneic DC can be used for DC-based cancer immunotherapy.

• Korean Journal of Radiology
• /
• 제23권9호
• /
• pp.911-920
• /
• 2022

Objective: ⁶⁸Ga-NGUL is a novel prostate-specific membrane antigen (PSMA)-targeting tracer based on Glu-Urea-Lys derivatives conjugated to a 1,4,7-triazacyclononane-N,N',N''-triacetic acid (NOTA) chelator via a thiourea-type short linker. This phase I clinical trial of ⁶⁸Ga-NGUL was conducted to evaluate the safety and radiation dosimetry of ⁶⁸Ga-NGUL in healthy volunteers and the lesion detection rate of ⁶⁸Ga-NGUL in patients with prostate cancer. Materials and Methods: We designed a prospective, open-label, single-arm clinical trial with two cohorts comprising six healthy adult men and six patients with metastatic prostate cancer. Safety and blood test-based toxicities were monitored throughout the study. PET/CT scans were acquired at multiple time points after administering ⁶⁸Ga-NGUL (2 MBq/kg; 96-165 MBq). In healthy adults, absorbed organ doses and effective doses were calculated using the OLINDA/EXM software. In patients with prostate cancer, the rates of detecting suspicious lesions by ⁶⁸Ga-NGUL PET/CT and conventional imaging (CT and bone scintigraphy) during the screening period, within one month after recruitment, were compared. Results: All 12 participants (six healthy adults aged 31-32 years and six prostate cancer patients aged 57-81 years) completed the clinical trial. No drug-related adverse events were observed. In the healthy adult group, ⁶⁸Ga-NGUL was rapidly distributed, with the highest uptake in the kidneys. The median effective dose coefficient was calculated as 0.025 mSv/MBq, and cumulative activity in the bladder had the highest contribution. In patients with metastatic prostate cancer, 229 suspicious lesions were detected using either ⁶⁸Ga-NGUL PET/CT or conventional imaging. Among them, ⁶⁸Ga-NGUL PET/CT detected 199 (86.9%) lesions and CT or bone scintigraphy detected 114 (49.8%) lesions. Conclusion: ⁶⁸Ga-NGUL can be safely applied clinically and has shown a higher detection rate for the localization of metastatic lesions in prostate cancer than conventional imaging. Therefore, ⁶⁸Ga-NGUL is a valuable option for prostate cancer imaging.

• 핵의학기술
• /
• 제14권2호
• /
• pp.133-137
• /
• 2010

유방암은 다른 장기에 비하여 뼈 전이와 임파절 전이가 잘 일어나는 질환으로 알려져 있으며, 유방암 수술 전, 후로 핵의학 검사인 전신 뼈 검사와 감시림프절 검사가 많이 시행되고 있다. 감시림프절 위치 파악 검사는 감시림프절에 정확 위치를 파악을 위해 시행되며, 유방암 수술 시 감시림프절을 파악 하는데 중요한 정보를 제공해 주게 된다. 본 연구에서는 감시림프절 위치 파악 검사 시 해부학적인 위치정보를 좀 더 명확하게 하기 위해 감시림프절 위치 파악 검사 전날 전신 뼈 검사를 시행하여 기존에 Flood 선원을 이용한 방법과 비교 평가하여 영상의 유용성에대해 알아보고자 하였다. 2009년 1월부터 12월까지 본원에서 전신 뼈 검사와 감시 림프절 검사를 2일에 걸쳐 시행한 환자 22명(평균나이 $52{\pm}7.2$세)을 대상으로 하였고, 대조군으로는 $^{57}Co$ flood phantom을 이용하여 감시림프절에 위치를 파악한 환자 22명(평균나이 $57{\pm}6.5$세)을 대상으로 하였다. 정량적인 분석 방법으로 전신 뼈 검사 후에 감시림프절 검사를 시행한 영상에 감시림프절과 배후방사능에 관심영역을 그려 상대적 비율을 측정하였으며, 육안적인 분석 방법으로 전신 뼈 검사 후 감시림프절 검사를 진행한 영상과 $^{57}Co$ flood phantom을 이용한 영상을 핵의학과 전문의와 5년 이상의 실무경험을 가진 방사선사가 각각 5점 척도로 하여, Blind test하였다. 정량적인 분석 결과 감시림프절에 대해 배후방사능이 미치는 영향은 전면상에서 최대 14.2:1, 평균 8:1(SD${\pm}$3.48), 측면상에서 최대 14.7:1, 평균 8.5:1(SD${\pm}$3.42)값으로 감시림프절에 대해 배후방사능에 차이가 크게 나타났고, 전면상과 측면상에서도 큰 차이가 없었다. 육안적인 분석 결과 $^{57}Co$ flood phantom 영상과 뼈가 포함된 영상을 비교한 결과 $^{57}Co$ flood phantom 영상 $3.86{\pm}0.35$점, 뼈 영상이 $4.09{\pm}0.42$점으로 $^{57}Co$ flood phantom 영상 보다 높은 점수를 나타내었다. 감시림프절 위치 파악 검사에 경우 검사 전날 전신 뼈 검사를 진행하였을 때에 뼈의 배후방사능과 감시 림프절에 비율차이가 평균 8:1 이상으로 림프절에 위치를 파악 하는데 문제가 없었다. 또한 전신 뼈 영상을 체표윤곽도로 이용하게 되면, 다른 선원을 이용하지 않고도 감시림프절에 위치정보를 나타낼 수 있어서 술자와 환자의 불필요한 피폭을 방지하며, 영상의 질적 향상을 기대할 수 있을 것으로 사료 된다.

• 대한정형외과학회지
• /
• 제56권1호
• /
• pp.42-50
• /
• 2021

목적: 종양인공관절 주위 골절은 안정된 고정의 어려움과 골유합 후에도 골질 약화로 해리 및 재골절 위험이 많다. 피질골 지주 중첩 동종골 이식술을 종양인공관절 주위 골절에 적용하면 내고정도 쉽고, 골유합 기간도 단축되며, 합병증도 줄일 수 있을 것이라고 생각하였다. 본 연구는 종양인공관절 주위 골절 27예(30 골절)의 골절의 양상과 치료 후 재건 술식에 따른 생존율 및 합병증, 중첩 동종골 이식술 추가 여부에 따라 골유합 기간 및 기능적 결과가 차이가 있는지 분석하였다. 대상 및 방법: 골절 치료 시 판형 동종골 이식을 한 군 16예와 시행하지 않은 군 14예를 비교하였다. 분석항목은 종양인공관절 치환술부터 골절까지 기간, 골절의 양상, 골유합 기간 차이, 합병증, 및 기능적 결과를 기술하였다. 결과: 골절 양상은 unified classification system (UCS) B형이 21예(70.0%, 21/30)로 가장 많았으며 그 중 B1이 14예(46.7%, 14/30), B2가 1예(3.4%, 1/30), B3가 6예(20.0%, 6/30)였고 C형이 9예(30.0%, 9/30)였다. Kaplan-Meier 법에 의한 30 재건 부위의 5년, 10년 생존율은 각각 84.5%±4.18%, 42.2%±7.83%였다. 전체 30예의 골유합 기간은 평균 5.1개월(범위, 2.0-11.2개월)이었다. 동종골 이식군은 평균 3.5개월(범위, 2.0-6.26개월)로 고식적 고정군의 평균 7.2개월(범위, 4.0-11.2개월)보다 짧았다(p<0.0001). 최종 기능평가상 동종골 이식군은 평균 26.1점으로 고식적 고정군의 평균 20.9점보다 높았다(p<0.0001). 합병증은 4예로 모두 동종골을 사용하지 않은 군에서 있었다. 결론: 종양인공관절 주위 골절은 드물고 골유합도 비교적 잘 이루어지나 유합 후 합병증 최소화가 중요하다. 판형 중첩 동종골 이식술은 골유합 기간을 단축, 골질 증가, 해리위험성 감소 효과가 있으며 종양인공관절 주위 골절에 유용한 방법이다.

• 대한골관절종양학회지
• /
• 제14권1호
• /
• pp.51-55
• /
• 2008

골육종의 치료율이 높아짐에 따라 장기 추시 결과와 기능적인 결과에 대한 관심이 환자나 의료진 모두에게 중요한 문제가 되어가고 있다. 슬관절 주위의 악성 종양을 절제 후 재건 시 종양인공관절 치환술에 비해 정상적인 슬관절 구조물을 보존하는 사지구제 술식이 가능하다면 좋은 방법으로 생각된다. 그러나 장기적으로 바람직한 기능적 결과를 얻기 위해 절제연을 희생하면 안 될 것으로 생각된다. 저자들은 원위 대퇴골 간부 골육종 환자에서 광범위 이상의 절제연 확보가 가능하다고 판단되어 분절 절제 후 저온 열처리한 자가골을 이용하여 재건하였으나 술 후 44개월만에 국소재발 한 례를 경험하여 문헌 고찰과 함께 보고하는 바이다.

• Radiation Oncology Journal
• /
• 제5권2호
• /
• pp.75-82
• /
• 1987

원자력병원 싸이클로트론으로 발생되는 고에너지 속중성자선의 생물학적효과에 대한 연구의 일환으로 RBE를 측정하였다. 대상은 Walker 256 carcinosacoma 및 정상조직으로 마우스 위장관 및 골수를 이용하였고 단일 및 분할조사에 대한 반응을 관찰하였다. 마우스 공장소낭선세포의 단일전신조사에 의한 RBE는 2.8이었다. 단일조사시 이식암 Walker 250의 TCD 50에 대한 RBE, 마우스 골수 및 위장관의 RBE는 각각 1.9, 1.9, 1.5이었다. 분할조사시 Walker 256의 RBE는 분할횟수의 증가에 따라 감소하였고 1회 분할조사량의 증가에 따라 증가하였다.

• 대한약침학회지
• /
• 제19권3호
• /
• pp.213-224
• /
• 2016

Objectives: Ginseng Rh2+ is enzyme-treated ginseng extract containing high amounts of converted ginsenosides, such as compound k, Rh2, Rg3, which have potent anticancer activity. We conducted general and genetic toxicity tests to evaluate the safety of ginseng Rh2+. Methods: An acute oral toxicity test was performed at a high-level dose of 4,000 mg/kg/day in Sprague-Dawley (SD) rats. A 14-day range-finding study was also conducted to set dose levels for the 90-day study. A subchronic 90-day toxicity study was performed at dose levels of 1,000 and 2,000 mg/kg/day to investigate the no-observed-adverse-effect level (NOAEL) of ginseng Rh2+ and target organs. To identify the mutagenic potential of ginseng Rh2+, we conducted a bacterial reverse mutation test (Ames test) using amino-acid-requiring strains of Salmonella typhimurium and Escherichia coli (E. coli), a chromosome aberration test with Chinese hamster lung (CHL) cells, and an in vivo micronucleus test using ICR mice bone marrow as recommended by the Korean Ministry of Food and Drug Safety. Results: According to the results of the acute oral toxicity study, the approximate lethal dose (ALD) of ginseng Rh2+ was estimated to be higher than 4,000 mg/kg. For the 90-day study, no toxicological effect of ginseng Rh2+ was observed in body-weight changes, food consumption, clinical signs, organ weights, histopathology, ophthalmology, and clinical pathology. The NOAEL of ginseng Rh2+ was established to be 2,000 mg/kg/day, and no target organ was found in this test. In addition, no evidence of mutagenicity was found either on the in vitro genotoxicity tests, including the Ames test and the chromosome aberration test, or on the in vivo in mice bone marrow micronucleus test. Conclusion: On the basis of our findings, ginseng Rh2+ is a non-toxic material with no genotoxicity. We expect that ginseng Rh2+ may be used as a novel adjuvant anticancer agent that is safe for long-term administration.

• Archives of Plastic Surgery
• /
• 제34권4호
• /
• pp.448-454
• /
• 2007

Purpose: The objective of this study was to evaluate the outcomes of using the free flap in the reconstruction of maxillary defects. Methods: 27 consecutive cases of maxillary reconstruction with free flap were reviewed. All clinical data were analyzed, including ideal selection of flap, time of reconstruction, recurrence of cancer, postoperative complications, flap design, and follow-up results. The main operative functional items, including speech, oral diet, mastication, eye globe position and function, respiration, and aesthetic results were evaluated. Results: Among the 24 patients who underwent maxillary reconstruction with the free flap, 14 patients underwent immediate reconstruction after maxillary cancer ablation, and 10 patients underwent delayed reconstruction. There occurred 1 flap loss. Recurrences of the cancer after the reconstruction happened in 2 cases. Postoperative complications were 3 cases of gravitational ptosis of the flap, 2 cases of the nasal obstruction, and 1 case of fistula formation. Out of 27 free flaps, there were 15 latissimus dorsi myocutaneous flaps, 5 radial forearm, 4 rectus abdominis myocutaneous flaps, 1 scapular flap, 2 fibula osteocutaneous flap, respectively. Flaps were designed such as 1 lobe in 9 cases, 2 lobes in 9 cases, and 3 lobes in 5 cases. Among the 14 patients who had intraoral defect or who had palatal resection surgery, 2 patients complained the inaccuracy of the pronunciation due to the ptosis of the flap. It was corrected by the reconstruction of the maxillary buttress and hung the sling to the upper direction. All of the 14 patients were able to take unrestricted diets. In 6 patients who had reconstruction of inferior orbital wall with rib bone graft, they preserved normal vision. Aesthetically, most of the patients were satisfied with the result. Conclusion: LD free flap is suggested in uni-maxilla defect as the 1st choice, and fibular osteocutaneous flap and calvarial bone graft to cover the larger defect in bi-maxilla defect.

• Asian Pacific Journal of Cancer Prevention
• /
• 제13권10호
• /
• pp.5319-5321
• /
• 2012

Objective: To observe efficacy and side effects, as well as the impact on quality of life, of Kanglaite$^{(R)}$ (Coix Seed Oil) injections combined with chemotherapy in the treatment of advanced gastric cancer patients. Method: A consecutive cohort of 60 patients were divided into two groups: the experimental group receiving Kanglaite$^{(R)}$ Injection combined with chemotherapy and the control group with chemotherapy alone. After more than two courses of treatment, efficacy, quality of life and side effects were evaluated. Results: The response rate and KPS score of experimental group were significantly improved as compared with those of the control group (P<0.05). In addition, gastrointestinal reactions and bone marrow suppression were significantly lower than in the control group (P<0.05). Conclusions: Kanglaite$^{(R)}$ Injection enhanced efficacy and reduced the side effects of chemotherapy, improving quality of life of gastric cancer patients; use of Kanglaite$^{(R)}$ injections deserves to be further investigated in randomized control clinical trails.