• Asian Pacific Journal of Cancer Prevention
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• 제16권10호
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• pp.4363-4368
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• 2015

Background: The tumor-stroma ratio (TSR) represents the percentage of neoplastic cell components compared to the combined area of neoplastic cells and the surrounding tumor-induced stroma. A low TSR (predomination of stromal component) has been demonstrated to be an independent adverse prognostic factor in cancers of several organs. In cervical carcinoma patients, TSR has been evaluated in only one previous study with different histological types. The present study aimed to assess the prognostic value of TSR in early stage cervical cancer patients with adenocarcinoma histology only. Materials and Methods: Histological slides of patients with early stage (IB-IIA) cervical adenocarcinoma who underwent surgical treatment between January 2003 and December 2011 were reviewed. Patients who had received preoperative chemotherapy were excluded. TSR was categorized as low (<50%) and high (${\geq}50%$). Correlations between TSR and clinicopathological variables were evaluated. Prognostic values of TSR and other variables were estimated using Cox's regression. Results: Of 131 patients; 38 (29.0%) had low TSR and 93 (71.0%) had high TSR. The patients with low TSR had significantly higher proportions of deep cervical stromal invasion (outer third of wall, p=0.011; residual stroma less than 3 mm, p=0.008) and parametrial involvement (p=0.026). Compared to the patients with high TSR, those with low TSR tended to have lower 5-year disease-free survival rate (83.8% versus 88.9%) and overall survival rate (85.6% versus 90.3%), although the differences were not statistically significant. Low TSR was significantly associated with decreased overall survival in univariate analysis (HR 2.7; 95% CI 1.0-7.0; p=0.041), but not in multivariate analysis. TSR was not significantly associated with decreased disease-free survival. Conclusions: Low TSR is associated with decreased overall survival in patients with early stage cervical adenocarcinoma treated by surgery. However, it was not found to be an independent prognostic predictor in this study.

• Journal of Chest Surgery
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• 제41권2호
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• pp.160-169
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• 2008

배경: 혈관질환의 수술에 사용되는 인공 도관의 막힘과 문합부위의 좁아짐 등을 개선하기 위한 방법으로 조직공학적인 방법과 자가 세포를 이용한 인공혈관의 제작이 대안으로 대두되고 있다. 저자들은, 생흡수성이 있는 고분자 폴리머 지지체와 자가 골수세포를 이용한 인공혈관으로 생체실험을 시행하였다. 대상 및 방법: 생분해성 고분자 재료인 poly (lactide-co-${\varepsilon}$-caprolactone) (PLCL)과 poly(glycolic acid) (PGA) fiber로 혈관용 지지체를 제작한 후, 피실험 동물의 골수를 채취하여 혈관 내피 세포와 평활근 세포로 분열시켜 배양한 후 혈관 지지체위에 이식하였다. 만들어진 인공 혈관을 잡견의 복부대동맥에 이식한 후 3주 후에 혈관 조영술을 시행하고, 안락사 후에 혈관을 제거하여 조직학적 검사를 시행하였다. 결과: 6마리의 잡견 중 2마리에서 수술 후 10일에 혈관 지지체의 균열에 의한 대량 출혈로 사망하였다. 나머지 4마리의 잡견은 수술 후 3주까지 생존하였으며, 혈관 조영술상 혈관의 막힘이나 좁아짐은 발견되지 않았다. 인공 혈관의 내면은 작은 혈전들이 붙어 있었으며, 조직학 검사에서 정상 혈관과 유사한 3층의 구조를 나타내었다. 또한 면역화학 검사에서 혈관 내피세포와 혈관 평활근 세포가 재생된 것을 확인하였다. 결론: 고분자 폴리머와 자가 골수세포를 이용한 인공혈관은 생체 내에서 정상혈관과 유사한 모양으로 재생이 가능함을 보여주었다. 그러나, 동맥압력에 견디기 위해 혈관 지지체의 물성에 대한 개량과 충분한 양의 혈관 세포를 얻기 위한 연구가 더 필요할 것으로 생각된다.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제39권
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• pp.8.1-8.8
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• 2017

Background: For an effective bone graft for reconstruction of the maxillofacial region, an adequate vascular network will be required to supply blood, osteoprogenitor cells, and growth factors. We previously reported that the secretomes of bone marrow-derived mesenchymal stem cells (MSC-CM) contain numerous growth factors such as insulin-like growth factor (IGF)-1, transforming growth factor $(TGF)-{\beta}1$, and vascular endothelial growth factor (VEGF), which can affect the cellular characteristics and behavior of regenerating bone cells. We hypothesized that angiogenesis is an important step for bone regeneration, and VEGF is one of the crucial factors in MSC-CM that would enhance its osteogenic potential. In the present study, we focused on VEGF in MSC-CM and evaluated the angiogenic and osteogenic potentials of MSC-CM for bone regeneration. Methods: Cytokines in MSC-CM were measured by enzyme-linked immunosorbent assay (ELISA). Human umbilical vein endothelial cells (HUVECs) were cultured with MSC-CM or MSC-CM with anti-VEGF antibody (MSC-CM + anti-VEGF) for neutralization, and tube formation was evaluated. For the evaluation of bone and blood vessel formation with micro-computed tomography (micro-CT) and for the histological and immunohistochemical analyses, a rat calvarial bone defect model was used. Results: The concentrations of IGF-1, VEGF, and $TGF-{\beta}1$ in MSC-CM were $1515.6{\pm}211.8pg/mL$, $465.8{\pm}108.8pg/mL$, and $339.8{\pm}14.4pg/mL$, respectively. Tube formation of HUVECs, bone formation, and blood vessel formation were increased in the MSC-CM group but decreased in the MSC-CM + anti-VEGF group. Histological findings suggested that new bone formation in the entire defect was observed in the MSC-CM group although it was decreased in the MSC-CM + anti-VEGF group. Immunohistochemistry indicated that angiogenesis and migration of endogenous stem cells were much more abundant in the MSC-CM group than in the MSC-CM + anti-VEGF group. Conclusions: VEGF is considered a crucial factor in MSC-CM, and MSC-CM is proposed to be an adequate therapeutic agent for bone regeneration with angiogenesis.

• 동의생리병리학회지
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• 제21권6호
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• pp.1549-1554
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• 2007

To verify the effects of JAUN-1, which is a water-extracted herbal mixture, on gastroenteric disorders induced by 0.1 percent of iodoacetamide (IA) in rats. We divided four groups, $Na{\&quot;{\i}}ve$ + Distilled Water (DW), 0.1% IA + DW, 0.1% IA + Proton pump inhibitor (Lansoprazole, 5 mg/kg) and 0.1% IA + Herbal mixture (JAUN-1, 50mg/kg) and performed following experimental methods to confirm its advantageous effects against ulcerogenic stomach in rats induced by 0.1% IA; cell cytotoxicity, analysis of lesions score, Hematoxylin & Eosin (H&E) stain, RT-PCR for ${\beta}-actin$, COX-1 and COX-2 and evaluation of intestinal prokinetic activity. No cytotoxicity was elucidated at the concentration of 1, 5, 10, 50, 100, $500\;{\mu}g/ml$ and 1mg/ml JAUN-1 through MTT Assay using by human stomach epithelial AGS cells, respectively. In addition, the JAUN-1 treated group and the lansoprazole treated group significantly decreased in lesions score compared to the DW treated group in the gastritis induced rat model, and results of immunohistochemistry by H&E staining showed that histological recovery in Proton Pump Inhibitor (PPI) and JAUN-1 treated groups rather than the DW administrated group. Another outcome was that ${\beta}-actin$ relative COX-2 expression level was significantly promoted in the DW treated group while ${\beta}-actin$ relative COX-1 expression level was no meaningful change in this rat model. Finally, intestinal prokinetic activity was recovered from low level of prokinetic activity due to 0.1% IA induced gastritis to the similar level of Normal group. These results suggested that JAUN-1 may have beneficial effects against 0.1% IA-induced gastritis rat model through decreasing lesions score, histological recovery, ${\beta}-actin$ relative COX-1, 2 expression level and prokinetic activity.

• Korean Journal of Radiology
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• 제20권5호
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• pp.830-843
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• 2019

Objective: To examine the potential of intravoxel incoherent motion (IVIM) and blood oxygen level-dependent (BOLD) magnetic resonance imaging for detecting renal changes after iodinated contrast-induced acute kidney injury (CI-AKI) development in a diabetic rabbit model. Materials and Methods: Sixty-two rabbits were randomized into 2 groups: diabetic rabbits with the contrast agent (DCA) and healthy rabbits with the contrast agent (NCA). In each group, 6 rabbits underwent IVIM and BOLD imaging at 1 hour, 1 day, 2 days, 3 days, and 4 days after an iohexol injection while 5 rabbits were selected to undergo blood and histological examinations at these specific time points. Iohexol was administrated at a dose of 2.5 g I/kg of body weight. Further, the apparent transverse relaxation rate (R2^*), average pure molecular diffusion coefficient (D), pseudo-diffusion coefficient (D^*), perfusion fraction (f) were calculated. Results: The D and f values of the renal cortex (CO) and outer medulla (OM) were significantly decreased compared to baseline values in the 2 groups 1 day after the iohexol injection (p < 0.05). A marked reduction in the D^* values for both the CO and OM was also observed after 1 hour in each group (p < 0.05). In the OM, a persistent elevation of the R2^* was detected for 4 days in the DCA group (p < 0.05). Histopathological changes were prominent, and the pathological features of CI-AKI aggravated in the DCA group until day 4. The D, f, and R2^* values significantly correlated with the histological damage scores, hypoxia-inducible transcription factor-1α expression scores, and serum creatinine levels. Conclusion: A combination of IVIM and BOLD imaging may serve as a noninvasive method for detecting and monitoring CI-AKI in the early stages in the diabetic kidney.

• Journal of Periodontal and Implant Science
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• 제40권3호
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• pp.132-138
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• 2010

Purpose: The purpose of this study was to compare the bone regeneration effects of cortical, cancellous, and cortico-cancellous human bone substitutes on calvarial defects of rabbits. Methods: Four 8-mm diameter calvarial defects were created in each of nine New Zealand white rabbits. Freeze-dried cortical bone, freeze-dried cortico-cancellous bone, and demineralized bone matrix with freeze-dried cancellous bone were inserted into the defects, while the non-grafted defect was regarded as the control. After 4, 8, and 12 weeks of healing, the experimental animals were euthanized for specimen preparation. Micro-computed tomography (micro-CT) was performed to calculate the percent bone volume. After histological evaluation, histomorphometric analysis was performed to quantify new bone formation. Results: In micro-CT evaluation, freeze-dried cortico-cancellous human bone showed the highest percent bone volume value among the experimental groups at week 4. At week 8 and week 12, freeze-dried cortical human bone showed the highest percent bone volume value among the experimental groups. In histologic evaluation, at week 4, freeze-dried cortico-cancellous human bone showed more prominent osteoid tissue than any other group. New bone formation was increased in all of the experimental groups at week 8 and 12. Histomorphometric data showed that freeze-dried cortico-cancellous human bone showed a significantly higher new bone formation percentile value than any other experimental group at week 4. At week 8, freeze-dried cortical human bone showed the highest value, of which a significant difference existed between freeze-dried cortical human bone and demineralized bone matrix with freeze-dried cancellous human bone. At week 12, there were no significant differences among the experimental groups. Conclusions: Freeze-dried cortico-cancellous human bone showed swift new bone formation at the 4-week healing phase, whereas there was less difference in new bone formation among the experimental groups in the following healing phases.

• Archives of Plastic Surgery
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• 제41권6호
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• pp.661-667
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• 2014

Background Tissue expansion is an effective and valuable technique for the reconstruction of large skin lesions and scars. This study aimed to evaluate the applicability and safety of a newly designed skin expanding bioreactor system for maximizing the graft area and minimizing the donor site area. Methods A computer-controlled biaxial skin bioreactor system was used to expand skin in two directions while the culture media was changed daily. The aim was to achieve an expansion speed that enabled the skin to reach twice its original area in two weeks or less. Skin expansion and subsequent grafting were performed for 10 patients, and each patient was followed for 6 months postoperatively for clinical evaluation. Scar evaluation was performed through visual assessment and by using photos. Results The average skin expansion rate was $10.54%{\pm}6.25%$; take rate, $88.89%{\pm}11.39%$; and contraction rate, $4.2%{\pm}2.28%$ after 6 months. Evaluation of the donor and recipient sites by medical specialists resulted in an average score of 3.5 (out of a potential maximum of 5) at 3 months, and 3.9 at 6 months. The average score for patient satisfaction of the donor site was 6.2 (out of a potential maximum of 10), and an average score of 5.2 was noted for the recipient site. Histological examination performed before and after the skin expansion revealed an increase in porosity of the dermal layer. Conclusions This study confirmed the safety and applicability of the in vitro skin bioreactor, and further studies are needed to develop methods for increasing the skin expansion rate.

• 한국임상수의학회지
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• 제32권5호
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• pp.410-416
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• 2015

골대체제는 지연유합이나 유합부전 그리고 골절술과 관절고정술 시 골편의 연속성 확립이 필요한 경우 골절의 주요 결손부위를 채우는데 주로 활용되고 있다. 본 연구에서는 오적골의 다양한 전처리 후 직경 5 mm 두께 2 mm의 형태로 가공하여 rhBMP-2의 담체로써 골전도력과 골유도력을 평가하고자 하였다. 결합조직의 두께는 2, 4주차 모두 오적골유래 hydroxyapatite 적용군(CBHA)에서 가장 유의성 있게 얇았다(p < 0.05). Radiologic gray-level histogram의 측정에서는 4주차에서 CBHA군이 산호유래 hydroxyapatite 적용군(CHA)군보다 유의성 있게 높게 나타났으며(p < 0.05), 12주차에서는 CHA군의 변화율이 가장 적었다. 전체 12주 동안의 변화율에서는 CBHA가 가장 많은 변화를 보였다. 폐쇄율에 있어서는 4, 8, 12주차 모두 CHA군이 다른 군에 비해 유의성 있게 높게 나타났으며(p < 0.05), 8주차에서는 bmp를 적용한 오적골 적용군(CB1bmp)이 CBHA군보다 유의성 있게 높게 나타났다(p < 0.05). 이상의 결과들은 CBHA가 생체 내에 적용하는 골대체재로서 골유도능력이 우수한 것으로 나타났다. 따라서 CBHA는 편평골에 있어 생체적 합성이 뛰어난 골대체재로 그 가치가 있는 것으로 생각되며, 수의 임상에 있어서 활용성이 매우 높을 것으로 사료된다.

• Journal of Radiation Protection and Research
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• 제24권1호
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• pp.17-22
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• 1999

이온화방사선이 동물 생식세포에 미치는 생화학적 및 형태학적 영향을 알아보기 위해 본 연구를 시행하였다. 미성숙 생쥐 (ICR, 3 주령)에 $\gamma$선을 선량 $LD_{80(30)}$으로 전신조사하였다. 방사선 조사 후 6 시간, 12 시간, 1 일, 그리고 2 일 후에 난소를 적출하였다. 난소에서 추출한 과립세포의 세포주기를 DNA에 대한 유세포 분석으로 분석하였다. 세포자연사를 확인할 수 있는 $A_0$ 세포주기는 이온화방사선이 조사된 실험군에서 대조군에 비해 현저히 높은 값을 보였다. 이온화방사선을 조사한 후 6 시간 군에서 TUNEL 면역조직화학 염색도를 나타낸 난포의 수가 대조군에 비해 현저히 증가하였다. 따라서, 본 실험의 결과 방사선 조사에 의해 유발되는 난포의 퇴화는 6 시간 이내에 급성으로 진행되는 과립세포의 세포자연사에 의해 매개됨을 알 수 있었다. 유세포분석기를 이용한 세포주기 평가는 방사선에 의해 유발되는 세포자연사 기작의 이해와 퇴화난포의 정량화를 위한 수단이 될 수 있다.

• Restorative Dentistry and Endodontics
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• 제35권1호
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• pp.5-12
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• 2010

본 연구에서는 인위적으로 노출시킨 비글견의 치수조직을 기존의 수산화칼슘제재와 MTA, 접착성 레진, 광중합형 수산화칼슘제재를 사용하여 직접치수복조한 후 각 재료에 따른 치수의 반응을 광학현미경 하에서 조직학적으로 관찰하여 비교분석하였다. 2마리 비글견의 36개 치아를 이용하여, 실험적으로 치수를 노출시키고 노출된 치수에 치수복조재를 적용한 후 와동은 복합레진으로 충전하여 직접치수복조술을 시행하였다: (1) Mineral Trioxide Aggregate (MTA: $ProRoot^{(R)}$ MTA, Dentsply, Tulsa, USA), (2) Clearfil SE Bond (Dentin adhesive system: Kuraray, Osaka, Japan), (3) Ultra-Blend (Photopolymerized Calcium hydroxide: Ultradent, South Jordan, USA), (4) Dycal (Quick setting Calcium hydroxide: LD Caulk Co., Milford, USA). 희생전 90일, 30일, 7일 전에 각 복조재별로 3개씩의 와동을 충전하였고 비글견을 희생시키고 조직시편을 제작하였다. 시편을 H&E 염색 후 광학 현미경으로 치수염증반응과 경조직 형성 정도를 관찰하였다. MTA 군은 초기에는 경조직 형성이 관찰되지 않고 치수조직의 위축과 부분괴사가 관찰되었으나 시간이 지나면서 경조직 형성이 관찰되었다. Clearfil SE Bond군은 초기에 염증세포의 침윤과 치수세포의 괴사를 관찰할 수 있었고 시간이 지날수록 치수 세포의 괴사가 더욱 진행한 양상을 보였다. Ultra-blend 군과 Dycal 군은 MTA 군과 비슷하게 초기에는 경조직 형성을 보이지 않고 중등도의 염증반응이 관찰되었으며 시간이 지나면서 경조직 형성이 관찰되었다. MTA, 수산화칼슘제재와 광중합 수산화칼슘제재는 초기의 치수염증반응 이후 조상아세포층, 상아질교 형성을 보여 직접치수복조재로 적당하였으며, 접착성 레진은 심한 염증반응과 치수 조직의 괴사 양상을 보여 직접치수복조재로 부적당하다는 결론을 얻을 수 있었다.