• Title/Summary/Keyword: Cell-guide

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Evaluation of response to stereotactic radiosurgery in patients with radioresistant brain metastases

  • Sayan, Mutlay;Mustafayev, Teuta Zoto;Sahin, Bilgehan;Kefelioglu, Erva Seyma Sare;Wang, Shang-Jui;Kurup, Varsha;Balmuk, Aykut;Gungor, Gorkem;Ohri, Nisha;Weiner, Joseph;Ozyar, Enis;Atalar, Banu
    • Radiation Oncology Journal
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    • 제37권4호
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    • pp.265-270
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    • 2019
  • Purpose: Renal cell carcinoma (RCC) and melanoma have been considered 'radioresistant' due to the fact that they do not respond to conventionally fractionated radiation therapy. Stereotactic radiosurgery (SRS) provides high-dose radiation to a defined target volume and a limited number of studies have suggested the potential effectiveness of SRS in radioresistant histologies. We sought to determine the effectiveness of SRS for the treatment of patients with radioresistant brain metastases. Materials and Methods: We performed a retrospective review of our institutional database to identify patients with RCC or melanoma brain metastases treated with SRS. Treatment response were determined in accordance with the Response Evaluation Criteria in Solid Tumors. Results: We identified 53 radioresistant brain metastases (28% RCC and 72% melanoma) treated in 18 patients. The mean target volume and coverage was 6.2 ± 9.5 mL and 95.5% ± 2.9%, respectively. The mean prescription dose was 20 ± 4.9 Gy. Forty lesions (75%) demonstrated a complete/partial response and 13 lesions (24%) with progressive/stable disease. Smaller target volume (p < 0.001), larger SRS dose (p < 0.001), and coverage (p = 0.008) were found to be positive predictors of complete response to SRS. Conclusion: SRS is an effective management option with up to 75% response rate for radioresistant brain metastases. Tumor volume and radiation dose are predictors of response and can be used to guide the decision-making for patients with radioresistant brain metastases.

Semaphoring mAb: a New Guide in RIT in Inhibiting the Proliferation of Human Skin Carcinoma

  • Liu, Yuan;Ma, Jing-Yue;Luo, Su-Ju;Sun, Chen-Wei;Shao, Li-Li;Liu, Quan-Zhong
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권3호
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    • pp.941-945
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    • 2015
  • Semaphoring is a transmembrane receptor which participates in many cytokine-mediated signal pathways that are closely related to the angiogenesis, occurrence and development of carcinoma. The present study was designed to access the effect of mono-antibody (mAb) guided radioimmunotherapy (RIT) on skin carcinoma and investigate the potential mechanisms. Semaphoring mAb was acquired from mice (Balb/c), purified with rProtein A column; purity, concentration and activity were tested with SDS-PAGE and indirect ELISA; specificity and expression on the cutanuem carcinoma line and tissue were tested by Western blotting; morphology change was assessed by microscopy. MTT assay and colony inhibition tests were carried out to test the influence on the proliferation of tumor cells; Western blotting was also carried out for expression of apoptosis-associated (caspase-3, Bax, Bcl-2) and proliferation-related (PI3K, p-Akt, Akt, p-ERK1/2, ERK1/2) proteins and analyse the change in signal pathways (PI3K/Akt and MEK/ERK). The purity of purified semaphorin mAb was 96.5% and the titer is about $1{\times}10^6$. Western blotting showed semaphoring mAb to have specifically binding stripes with semaphoring b1b2 protein, B16F10, and A431 cells at 39KDa, 100KDa and 130KDa, respectively. Positive expression was detected both in cutanuem carcinoma line and tissue and it mostly located in cell membranes. MMT assay revealed dose-relate and time-relate inhibitory effect of semaphorin mAb on A431 and B16F10. Colony inhibition tests also showed dose-relate inhibitory effects. Western blotting demonstrated the expression of apoptosis and proliferation-related protein and changes in signal pathway. In conclusion, we demonstrated that semaphorin is highly expressed on the tumor cell-surfaces and RIT with semaphorin mAb has effect in i nhibiting proliferation and accelerating apoptosis of tumor cells.

Pro-Apoptotic Activity of 4-Isopropyl-2-(1-Phenylethyl) Aniline Isolated from Cordyceps bassiana

  • Kim, Mi Seon;Lee, Yunmi;Sung, Gi-Ho;Kim, Ji Hye;Park, Jae Gwang;Kim, Han Gyung;Baek, Kwang Soo;Cho, Jae Han;Han, Jaegu;Lee, Kang-Hyo;Hong, Sungyoul;Kim, Jong-Hoon;Cho, Jae Youl
    • Biomolecules & Therapeutics
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    • 제23권4호
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    • pp.367-373
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    • 2015
  • Cordyceps species including Cordyceps bassiana are a notable anti-cancer dietary supplement. Previously, we identified several compounds with anti-cancer activity from the butanol fraction (Cb-BF) of Cordyceps bassiana. To expand the structural value of Cb-BF-derived anti-cancer drugs, we employed various chemical moieties to produce a novel Cb-BF-derived chemical derivative, KTH-13-amine-monophenyl [4-isopropyl-2-(1-phenylethyl) aniline (KTH-13-AMP)], which we tested for anti-cancer activity. KTH-13-AMP suppressed the proliferation of MDA-MB-231, HeLa, and C6 glioma cells. KTH-13-AMP also dose-dependently induced morphological changes in C6 glioma cells and time-dependently increased the level of early apoptotic cells stained with annexin V-FITC. Furthermore, the levels of the active full-length forms of caspase-3 and caspase-9 were increased. In contrast, the levels of total forms of caspases-3, caspase-8, caspase-9, and Bcl-2 were decreased in KTH-13-AMP treated-cells. We also confirmed that the phosphorylation of STAT3, Src, and PI3K/p85, which is linked to cell survival, was diminished by treatment with KTH-13-AMP. Therefore, these results strongly suggest that this compound can be used to guide the development of an anti-cancer drug or serve as a lead compound in forming another strong anti-proliferative agent.

The effect of nanoemulsified methionine and cysteine on the in vitro expression of casein in bovine mammary epithelial cells

  • Kim, Tae-Il;Kim, Tae-Gyun;Lim, Dong-Hyun;Kim, Sang-Bum;Park, Seong-Min;Lim, Hyun-Joo;Kim, Hyun-Jong;Ki, Kwang-Seok;Kwon, Eung-Gi;Kim, Young-Jun;Mayakrishnan, Vijayakumar
    • Asian-Australasian Journal of Animal Sciences
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    • 제32권2호
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    • pp.257-264
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    • 2019
  • Objective: Dairy cattle nutrient requirement systems acknowledge amino acid (AAs) requirements in aggregate as metabolizable protein (MP) and assume fixed efficiencies of MP used for milk protein. Regulation of mammary protein synthesis may be associated with AA input and milk protein output. The aim of this study was to evaluate the effect of nanoemulsified methionine and cysteine on the in-vitro expression of milk protein (casein) in bovine mammary epithelial cells (MAC-T cells). Methods: Methionine and cysteine were nonionized using Lipoid S 75 by high-speed homogenizer. The nanoemulsified AA particle size and polydispersity index were determined by dynamic light scattering correlation spectroscopy using a high-performance particle sizer instrument. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed to determine the cytotoxicity effect of AAs with and without nanoionization at various concentrations (100 to $500{\mu}g/mL$) in mammary epithelial cells. MAC-T cells were subjected to 100% of free AA and nanoemulsified AA concentration in Dulbecco's modified Eagle medium/nutrient mixture F-12 (DMEM/F12) for the analysis of milk protein (casein) expression by the quantitative reverse transcription polymerase chain reaction method. Results: The AA-treated cells showed that cell viability tended to decrease (80%) in proportion to the concentration before nanogenesis, but cell viability increased as much as 90% after nanogenesis. The analysis of the expression of genetic markers related to milk protein indicated that; ${\alpha}_{s2}$-casein increased 2-fold, ${\kappa}$-casein increased 5-fold, and the amount of unchanged ${\beta}$-casein expression was nearly doubled in the nanoemulsified methionine-treated group when compared with the free-nanoemulsified methionine-supplemented group. On the contrary, the non-emulsified cysteine-administered group showed higher expression of genetic markers related to milk protein ${\alpha}_{s2}$-casein, ${\kappa}$-casein, and ${\beta}$-casein, but all the genetic markers related to milk protein decreased significantly after nanoemulsification. Conclusion: Detailed knowledge of factors, such nanogenesis of methionine, associated with increasing cysteine and decreasing production of genetic markers related to milk protein (casein) will help guide future recommendations to producers for maximizing milk yield with a high level of milk protein casein.

신연 골형성술시 신연속도에 따른 골형성 관여 인자의 발현 (EXPRESSION OF OSTEOGENESIS RELATED FACTORS ACCORDING TO DISTRACTION RATE IN THE DISTRACTION OSTEOGENESIS)

  • 지유진;김여갑
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • 제34권3호
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    • pp.250-265
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    • 2008
  • Distraction osteogenesis is a well-established clinical treatment for limb length discrepancy and skeletal deformities. Appropriate mechanical tension-stress is believed not to break the callus but rather to stimulate osteogenesis. In contrast to fracture healing, the mode of bone formation in distraction osteogenesis is primarily intramembranous ossification. Although the biomechanical, histological, and ultrastructural changes associated with distraction osteogenesis have been widely described, the basic biology of the process is still not well known. Moreover, the molecular mechanisms in distraction osteogenesis remain largely unclear. Recent studies have implicated the growth factor cascade is likely to play an important role in distraction. And current reserch suggested that mechanical tension-stress modulates cell shape and phenotype, and stimulates the expression of the mRNA for bone matrix proteins. The purpose of this study is to examine the pattern of expression of growth factors($TGF-{\beta}1$, IGF-I, bFGF) and extracellular matrix proteins(osteoclacin, osteonectin) related to osteogenesis by osteodistraction of the mandible in rabbits. 24 rabbits is used for this experiment. Experimental group are gradual distraction(0.7mm, twice/day), acute distraction(1.4mm, twice/day) and control group is only osteotomized. After 5 days latency, osteotomic site is distracted for each 7 days and 3.5 days. Consolidation period is 28 days. The animal is sacrificed at the 3th, 7th, 14th, 28th. The distracted bone is examined by immunohistochemical analysis and RT-PCR analysis. The results obtained from this study were as follow : No significant difference was found on clinical examination according to distraction rate, but gradual distraction was shown to improve regenerate bone formation on radiographic and histologic examination. Growth factors and extracelluar matrix proteins expression increased in distraction group than control group. From these results, it could be stated that graudal distraction is shown to improve and accelerate bone formation and mechanical stress like distraction has considerable effects on osteogenesis related factors. And rabbit is the most appropriate animal model for further reseach on the molecular mechanisms that mediate osteodistraction. It is believed that understanding the biomolecular mechanisms that mediate distraction osteogenesis may guide the development of targeted strategies designed to improve distraction osteogenesis and accelerate bone healing.

비강 내 이물에 의한 만성 비염 치료를 위해 비강절개술 적용 증례 (Rhinotomy for Chronic Rhinitis by Nasal Foreign Body in a Dog)

  • 김지혜;박진욱;김종민;박성규;손진나;장동우;나기정;최석화;김근형
    • 한국임상수의학회지
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    • 제28권4호
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    • pp.452-456
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    • 2011
  • 5 year-old female Siberian husky which was 27 kg had presented with a recurrent rhinitis with chronic discharge and cough. A nasal foreign material had been suggested by a finding of a bone density ($0.3{\times}0.3$ cm) in the left nasal cavity on X-ray and CT-scanning. Soft tissue opacity in frontal sinus and nasal cavity was increased and foreign material was located beside turbinate bone in the left nasal. We found that there was the increase in the number of eosinophil and mast cell by the nasal cytology test. These results mentioned above indicated that the rhinitis by nasal foreign body was suspicious. We decided that the transfrontal rhinotomy could be the proper procedure to approach the material in this case. After rhinotomy, the foreign body and severe sticky discharge were removed. Drain was placed through the hole and into the frontal sinus and nasal cavity which were flushed two times a day for 7 days. The clinical signs such as cough and nasal discharge were shown to be improved in the every visiting for the re-check. On the $40^{th}$ day after surgery, we could confirm that the most of soft tissue density in the frontal sinus and nasal cavity was decreased by CT-scanning. However, foreign body was not identified by histological examination. For the treatment of chronic rhinitis caused by foreign body, the surgical method such as rhinotomy can be applied, when it is difficult to remove it in the guide of the nasal endoscope.

고유진동수 조절이 가능한 액체댐퍼의 건물응답 제어실험 (Experimental Verification of a Liquid Damper with Changeable Natural Frequency for Building Response Control)

  • 김동익;민경원;박지훈;김재건;황규석;길용식
    • 한국전산구조공학회논문집
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    • 제25권4호
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    • pp.323-330
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    • 2012
  • 본 연구진은 최근 U자 형태인 액체댐퍼의 수직관을 다수의 셀(사각 기둥)로 나누어 셀 상부를 개폐함에 따라 다양한 고유진동수를 쉽게 재현하는 새로운 멀티셀 액체댐퍼를 제시하였다. 이러한 댐퍼를 1층 건물 모형에 설치하여 진동대 실험을 수행하여 건물응답이 감소되는 것을 검증하였다. 64층의 풍응답인 가속도를 제어할 수 있도록 댐퍼를 설계하기 위하여 건물을 1자유도계로 축소하였다. 가속도 기반 상사비인 1/20를 적용하여 1층 건물 모형과 새로운 댐퍼를 제작하였다. 설계 진동수인 0.65Hz가 구현되도록 모형건물의 질량과 강성을 쉽게 조절할 수 있도록 탈부착식으로 제작하였다. 모형건물은 중량을 부담하는 질량부와 하부에 스프링과 LM guide가 설치된 구동부로 나누어서 제작되었다. 18개의 셀을 가지는 액체댐퍼를 제작하여 고유진동수 조절 범위가 0.65Hz~0.81Hz인 것을 파악하였다. 대형 진동대에 설치한 모형건물의 일방향 가진을 통하여 모형의 응답을 측정하고 모형상부에 멀티셀 액체댐퍼가 설치되었을 경우 모형의 응답을 측정하여 비교하였다. 진동대 가속도를 입력과 모형건물의 가속도를 출력으로 하는 전달함수를 통해 결과를 나타내었다. 예상한 바와 같이 멀티셀 액체댐퍼의 고유진동수를 건물의 진동수에 동조시켰을 경우 건물의 가속도 응답이 감소함을 알 수 있었다.

자연 고분자 : 상처 치료 재료로 활용 (Natural Origin Polymers: Applications as Wound Care Materials)

  • 파티 카라데니즈;성혜경;김한성
    • 생명과학회지
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    • 제29권3호
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    • pp.382-393
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    • 2019
  • 상처 치료는 전세계 인류에 영향을 미치는 보건 산업계의 관심사다. 당뇨병과 같은 대사증후군 유병률 증가로 상처에 의한 합병증의 위험이 높아지고 상처치유의 복잡함 때문에 상처의 치료와 관리가 어렵다. 전통적 상처 드레싱은 제한된 보호기능을 제공하며, 상처 드레싱의 치료 능력을 향상시키기 위해 생체고분자 기반의 드레싱들이 개발되고있다. 생체고분자는 생분해성이 뛰어나고 생체적합성이 좋으며 효과적인 상처 관리에 중요한 항균, 항염증, 지혈, 세포증식, 혈관성 활동 등 다양한 효과가 있다. 키토산, 셀룰로오스, 콜라겐, 히알루론산, 알긴산 등의 여러 생체고분자가 이미 상처치유제로 활용되고 있으며 생체고분자를 다른 고분자, 생체활성 분자 및 약물과 결합하여 생리학적 문제 없이 흉터를 최소화하는 새로운 상처 드레싱이 개발되고 있다. 본 논문에서는, 향후의 연구와 활용을 위한 현재의 생체고분자의 상처처리에 대해 알아보았다.

CRISPR/dCas9을 통한 NAGK 및 Reln 유전자 활성화에 의한 헌팅턴병 모델에서 단백질 응집체 제거 촉진 (Enhancement of Protein Aggregate Clearance in Huntington's Disease Model viaCRISPR/dCas9 Activation of NAGK and Reln Genes)

  • 옥타비아니 디야 파티마;다시 라주;하비바 사르민 움메이;최호진;문니 야스민 악타;석대현;메이니타 마리아 디야 누;문일수
    • 생명과학회지
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    • 제34권9호
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    • pp.609-619
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    • 2024
  • 신경퇴행성 질환은 신경세포 내 유독한 잘못 접힌 단백질의 축적으로 특징지어진다. 따라서 효과적인 예방 및 응집체 제거를 위한 전략이 치료에 중요하다. 세포질 다이네인(dynein)은 응집체를 세포 중심으로 운반하여 용해소체(lysosome)를 통해 자가포식 분해를 진행함으로써 응집체 제거에 중요한 역할을 한다. 이전 연구에서 우리는 N-아세틸글루코사민 키나제(NAGK)와 Reln에 의한 다이네인의 활성화 증거를 보고했다. 본 연구에서는 NAGK와 Reln의 발현 증가가 응집체 제거에 미치는 영향을 탐구했다. HEK293T 세포(인간 배아 신장 세포주)에서 NAGK와 Reln 유전자를 발현을 촉진시키기 위해 CRISPR/dCas9 활성화 시스템(CAS)을 사용하여 표적 특이적 20 nt 가이드 RNA를 인코딩하는 특정 플라스미드를 이용했다. 이러한 유전자 표현 촉진의 효과를 돌연변이 헌팅틴(mHtt, Q74) 응집체가 유도된 헌팅턴병 세포 모델인 HEK293T 세포와 일차 마우스 피질 신경세포에서 분석했다. 결과는 NAGK 또는 Reln, 혹은 이들의 조합에 의한 CAS 활성화가 Q74 응집체('응집체')를 가진 세포의 비율을 유의미하게 감소시켰음을 보여주었다. 이 효과는 다이네인 억제제 Ciliobrevin D와 자가포식 억제제 Chloroquine에 의해 반전되었다. 이는 다이네인 매개 자가포식이 응집체 제거에 역할을 함을 나타낸다. 이러한 발견은 표적 유전자 활성화를 통해 신경세포 건강을 증진시키기 위한 치료 전략의 기초를 제공한다.

혼합상토에 기비로 혼합된 NO3:NH4 비율이 토마토 플러그 묘 생장에 미치는 영향 (Impact of Pre-planting NO3:NH4 Ratios in Root Media on the Growth of Tomato Plug Seedlings)

  • 성좌경;이누리;최종명
    • 원예과학기술지
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    • 제34권5호
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    • pp.727-735
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    • 2016
  • 상토에 기비로 혼합된 질소의 $NO_3:NH_4$ 비율이 토마토 'Dotaerang Dia'의 플러그 묘 생장에 미치는 영향을 구명하기 위하여 본 연구를 수행하였다. 피트모스+코이어 더스트+펄라이트를 3.5:3.5:3.0(v/v/v)인 혼합상토를 조제하였고, 총 질소 농도가 $300mg{\cdot}L^{-1}$이면서, $NO_3:NH_4$ 비율이 100:0, 73:27, 50:50, 27:73, 0:100인 5처리를 만든 후 50구 플러그트레이에 충전하였다. 이후 종자를 파종하고 6주간 재배한 후 지상부 생육, 식물체 무기원소 함량 그리고 상토의 무기원소 농도를 조사 및 분석하였다. 파종 전 $NH_4$비율이 높을수록 상토의 EC가 높았지만, 플러그 묘의 생장이 진행될수록 모든 처리에서 상토의 EC가 낮아졌고 pH가 점차 상승하였다. 플러그 묘 생장은 $NO_3:NH_4$(50:50) 처리에서 초장 29.0cm, 초폭 26.4cm, 지상부 생체중 13.7g, 건물중 1.21g으로 가장 우수하였고 $NO_3:NH_4$(0:100)에서 초장 26.5cm, 초폭 24.1cm 그리고 지상부 생체중과 건물중이 각각 11.2g과 0.92g으로 가장 저조하였다. 모든 처리구의 질소 함량은 2.77-3.22% 범위에 포함되었으며 $NO_3:NH_4$(27:73) 처리에서 Fe, Mn 및 Zn의 함량은 가장 높았고, $NO_3:NH_4$(0:100)에서 가장 낮았다. 이상의 결과를 종합할 때 $NH_4$ 비율을 50% 이하로 조절하는 것이 토마토 플러그 묘의 재배를 위해 바람직하다고 판단하였다.