• Biotechnology and Bioprocess Engineering:BBE
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• 제7권2호
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• pp.67-75
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• 2002

The human complement receptor type 1 (CR 1, C3 b/C4b receptor) is a polymorphic membrane glycoprotein expressed on human erythrocytes, peripheral leukocytes, plasma and renal glomerular podocytes, which consists of transmembrane and cytoplasmic domains with 30 repeating homologous protein domains known as short consensus repeats (SCR). CR1 has been used as an inhibitor for inflammatory and immune system for the past several years. Recently; it is reported that CRl was found to suppress the hyper-acute rejection in xeno-transplantation and can be used to cure autoimmune diseases. A soluble form of CRl, called sCRl, is a recombinant CRl by cleaving the transmembrane domain at C-terminus and has been expressed in Chinese Hamster Ovary (CHO) cells. Several purification methods for sCR1 from CHO cells have been reported, but most of them require complicated steps at high cost. Moreover, such methods are mostly performed under the pH condition apt to denaturing sCR1 and causes sCRl losing its activity. We here report a rapid and efficient method to purify sCR1 from CHO cell. The new method consists of a two-stage of cell culture by cultivating cells in serum medium followed by serum-free medium, and a two-stage of column purification by means of heparin and gel filtration column chromatography. By using this novel method, sCR1 can be purified in a simple and effective way with high yield and purity, furthermore, the purified sCR1 was confirmed to retain its activity to suppress the complement activation in vivo and ex vivo.

• Childhood Kidney Diseases
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• 제12권1호
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• pp.11-22
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• 2008

Telomeres consist of tandem guanine-thymine(G-T) repeats in most eukaryotic chromosomes. Human telomeres are predominantly linear, double stranded DNA as they ended in 30-200 nucleotides(bases,b) 3'-overhangs. In DNA replication, removal of the terminal RNA primer from the lagging strand results in a 3'-overhang of uncopied DNA. This is because of bidirectional DNA replication and specificity of unidirectional DNA polymerase. After the replication, parental and daughter DNA strands have unequal lengths due to a combination of the end-replication problem and end-processing events. The gradual chromosome shortening is observed in most somatic cells and eventually leads to cellular senescence. Telomere shortening could be a molecular clock that signals the replicative senescence. The shortening of telomeric ends of human chromosomes, leading to sudden growth arrest, triggers DNA instability as biological switches. In addition, telomere dysfunction may cause chronic allograft nephropathy or kidney cancers. The renal cell carcinoma(RCC) in women may be less aggressive and have less genomic instability than in man. Younger patients with telomere dysfunction are at a higher risk for RCC than older patients. Thus, telomeres maintain the integrity of the genome and are involved in cellular aging and cancer. By studying the telomeric DNA, we may characterize the genetic determinants in diseases and discover the tools in molecular medicine.

• 생명과학회지
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• 제29권3호
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• pp.318-324
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• 2019

두경부암은 전세계에서 발병률이 여섯 번째로 높은 암으로 그동안 수술적 치료를 선호하였으나 광범위한 절제에 따른 기능적 장애로 인해 항암치료에 대한 관심이 높아지고 있다. 두경부암에서 cisplatin이 가장 많이 사용되는 항암제이나 cisplatin 내성이 문제가 되고 있다. 따라서 부작용은 줄이고, 약제내성 기전에 대해 이해하여 암세포의 사멸은 증대시키는 새로운 항암제의 개발이 필요하다. Survivin은 inhibitor of apoptosis proteins (IAPs) family 중 하나로 두경부암에서 과발현되어 있다. YM155는 survivin을 억제하는 분자로 본 연구를 통해 YM155의 처리 후 두경부 암세포의 세포자멸사가 유도되며, 뇌암 세포와 신장암 세포에서도 세포자멸사가 유도됨을 확인할 수 있었다. 반면에 정상세포인 mesangial cells에는 YM155가 세포자멸사에 영향을 주지 않았다. YM155는 caspase의 활성화를 통해 세포자멸사를 촉진하며, anti-apoptotic protein인 c-FLIP, Mcl-1, survivin의 발현을 저해하는 것으로 확인되었다. YM155는 두경부 뿐만 아니라 다른 장기의 악성종양 치료법의 개발에 활용 될 수 있을 것으로 생각된다.

• BMB Reports
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• 제39권5호
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• pp.469-478
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• 2006

Vascular endothelial growth factor (VEGF)-A, a major regulator for angiogenesis, binds and activates two tyrosine kinase receptors, VEGFR1 (Flt-1) and VEGFR2 (KDR/Flk-1). These receptors regulate physiological as well as pathological angiogenesis. VEGFR2 has strong tyrosine kinase activity, and transduces the major signals for angiogenesis. However, unlike other representative tyrosine kinase receptors which use the Ras pathway, VEGFR2 mostly uses the Phospholipase-$C{\gamma}$-Protein kinase-C pathway to activate MAP-kinase and DNA synthesis. VEGFR2 is a direct signal transducer for pathological angiogenesis including cancer and diabetic retinopathy, thus, VEGFR2 itself and the signaling appear to be critical targets for the suppression of these diseases. VEGFR1 plays dual role, a negative role in angiogenesis in the embryo most likely by trapping VEGF-A, and a positive role in adulthood in a tyrosine kinase-dependent manner. VEGFR1 is expressed not only in endothelial cells but also in macrophage-lineage cells, and promotes tumor growth, metastasis, and inflammation. Furthermore, a soluble form of VEGFR1 was found to be present at abnormally high levels in the serum of preeclampsia patients, and induces proteinurea and renal dysfunction. Therefore, VEGFR1 is also an important target in the treatment of human diseases. Recently, the VEGFR2-specific ligand VEGF-E (Orf-VEGF) was extensively characterized. Interestingly, the activation of VEGFR2 via VEGF-E in vivo results in a strong angiogenic response in mice with minor side effects such as inflammation compared with VEGF-A, suggesting VEGF-E to be a novel material for pro-angiogenic therapy.

• Tuberculosis and Respiratory Diseases
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• 제39권4호
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• pp.310-317
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• 1992

연구배경 : Angiotensin-converting enzyme (ACE)은 인체의 여러 조직 또는 혈청내에 존재하는 glycoprotein peptidyldipeptide hydrolase로써 여러 종류의 peptides에서 dipeptides를 떼어내는 역할을 담당한다. 이러한 ACE는 주로는 혈관 내피 세포에서 형성되며 인체에서는 폐에 가장 많은 모세혈관들이 존재하므로 ACE가 혈중에 존재하는 기질과 작용하는 곳 또한 폐의 모세 혈관내이다. 임상적으로 ACE는 유육종증의 진단 및 경과 관찰에 이용되며 기타 급성 또는 만성 폐질환에서 혈청 ACE 활성도가 감소된다는 사실이 보고되고 있다. 그러나 한 시점에서의 혈청 ACE 활성도는 폐손상의 유무 및 그 정도를 잘 반영한다고 볼 수는 없으나 시간 간격을 두고 차례대로 측정한 값은 예후와 관련이 있다고 알려져 있다. 이에 저자는 폐암환자를 대상으로 혈청내의 ACE 활성도를 측정하여 이들 환자에 있어서 향후 예후 예측의 지표로써의 가능성을 알아보고자 하였다. 방법 : 연구대상은 새로 진단된 폐암 환자로 하였고 대조군으로는 연구 대상군과 비슷한 연령군으로 하되 두군 모두에서 고혈압, 심장질환, 간질환, 신장 질환 그리고 폐암 이외의 기타 폐질환이 있는 사람은 제외시켰다. 연구대상군은 편평상피세포 폐암환자 19명, 선암폐암환자 13명, 소세포 폐암환자 9명 이었다. 결과 : 1) 편평상피세포 폐암환자의 혈청내 ACE 활성도는 $36.2{\pm}14.2$ U/L 이었고 선암 폐암환자는 $46.0{\pm}18.7$ U/L, 소세포 폐암환자는 $45.7{\pm}14.1$ U/L, 대조군은 $41.4{\pm}18.7$ U/L로 폐암환자의 ACE 활성도는 대조군과 차이가 없었으며 폐암의 세포형에 따라서도 차이가 없었고 폐암의 병기에 따라서도 ACE 활성도는 차이가 없었다. 2) 편평상피세포 폐암환자 4명과 선암 폐암환자 4명은 폐암의 치료로써 폐절제술을 받았으며 수술 전후 ACE 활성도는 편평세포 폐암환자가 수술전 $35.8{\pm}13.9$ U/L, 수술후 $12.5{\pm}3.9$ U/L로 의미있게 감소하였으며 선암 폐암환자에서는 각각 $47.1{\pm}5.9$ U/L, $15.0{\pm}3.9$ U/L로 수술후 의미있게 감소하였다. 3) 편평상피 세포 폐암환자중 3명과 선암 폐암환자 4명에 대하여 항암제를 투여받은 3개월에 걸쳐 측정한 ACE 활성도는 유의한 변화가 없었으며 임상적으로도 폐암의 호전은 없었다. 4) 소세포 폐암환자 9명은 3개월동안의 항암제 투여 중 임상적으로는 호전이 있었으나 혈청내 ACE 활성도는 의미있는 변화가 없었다. 결론 : 이상에서 폐정제술후 혈청내 ACE 활성도는 감소됨을 알 수 있었으나 폐암의 세포형, 병기, 임상적 호전과 혈청내 ACE 활성도는 연관이 없어 혈청 ACE 활성도는 폐암환자의 질병 경과 판정의 지표로써 부적합함을 알 수 있었다.

• 한국약용작물학회지
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• 제25권4호
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• pp.231-237
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• 2017

Background: Cisplatin is one of the most extensively used chemotherapeutic agents for the treatment of cancer, including bladder, and ovarian cancers. However, it has been shown to induce nephrotoxicity, despite being an outstanding anti-cancer drug. In this study, we investigated the protective effect of dopaol ${\beta}$-D-glucoside (dopaol) on cisplatin-induced nephrotoxicity. Methods and Results: To confirm the protective effect of dopaol on cisplatin-induced nephrotoxicity, HK-2 cells were treated with $20{\mu}M$ cisplatin and $80{\mu}M$ dopaol. Cisplatin increased apoptosis, caspase-3 activity and mitochondrial dysfunction; however pretreatment with $80{\mu}M$ dopaol successfully attenuated apoptosis, caspase-3 activity and mitochondrial dysfunction. To evaluate the protective effect dopaol on cisplatin-induced nephrotoxicity in vivo, we used an animal model (balb/c mice, 20 mg/kg, i.p. once/day for 3 day). The results were similar to those obtained using HK-2 cells; renal tubular damage and neutrophilia induced by cisplatin reduced following dopaol injection (10 mg/kg, i.p. once/day for 3 day). Conclusions: These results indicate that dopaol treatment reduced cisplatin-induced nephrotoxicity in vitro and in vivo, and can be used to treat cisplatin-induced nephrotoxicity. However, further studies are required to determine the toxicity high dose dopaol and the signal pathways involved in its mechanism of action in animal models.

• Journal of Nutrition and Health
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• 제53권1호
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• pp.1-12
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• 2020

본 연구에서는 고혈당으로 인해 유발되는 당뇨병성 신장병증의 대표적인 증상인 사구체 경화증을 완화시키는 nobiletin의 효능에 대해 알아보고자 하였다. 신장 세포인 HRMC를 이용하여 고혈당에서의 세포외 기질 축적 단백질의 발현과 경화에 관여하는 신호 전달 억제 효능을 확인한 결과 nobiletin은 고혈당의 자극에 의해 증가하는 섬유화 단백질인 collagen IV, fibronectin 그리고 CTGF의 발현을 억제하였으며, 여기에 관여하는 TGF-β1-Src-caveolin-1 신호 전달 경로를 통해 사구체 경화증을 억제하는 것을 확인하였다. 따라서 nobiletin은 고혈당으로 유도된 당뇨병성 신장병증에 있어 사구체 경화증을 예방하는 기능성 성분으로서의 활용 가능성을 확인하였다.

• Nuclear Medicine and Molecular Imaging
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• 제40권2호
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• pp.82-89
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• 2006

Bone metastasis is a common sequelae of solid malignant tumors such as prostate, breast, lung, and renal cancers, which can lead to various complications, including fractures, hypercalcemia, and bone pain, as well as reduced performance status and quality of life it occurs as a result of a complex pathophysiologic process between host and tumor cells leading to cellular invasion, migration adhesion, and stimulation of osteoclastic and osteoblastic activity. Several sequelae occur as a result of osseous metastases and resulting bone pain can lead to significant debilitation. A multidisciplinary approach is usually required not only to address the etiology of the pain and its complicating factors but also to treat the patient appropriately. Pharmaceutical therapy of bone pain, includes non-steroidal analgesics, opiates, steroids, hormones, bisphosphonates, and chemotherapy. While external beam radiation therapy remains the mainstay of pain palliation of a solitary lesions, bone seeking radiopharmaceuticals have entered the therapeutic armamentarium for the treatment of multiple painful osseous lesions. $^{32}P,\;^{89}SrCl,\;^{153}Sm-EDTMP,\;^{188}Re/^{186}Re-HEDP,\;and\;^{177}Lu-EDTMP$ can be used to treat painful osseous metastases. These various radiopharmaceuticals have shown good efficacy in relieving bone pain secondary to bone metastasis. This systemic form of metabolic radiotherapy is simple to administer and complements other treatment options. This has been associated with improved mobility in many patients, reduced dependence on narcotic and non-narcotic analgesics, improved performance status and quality of life, and, in some studios, improved survival. All of these agents, although comprising different physical and chemical characteristics, offer certain advantages in that they are simple to administer, are well tolerated by the patient if used appropriately, and can be used alone or in combination with the other forms of treatment. This article illustrates the salient features of these radiopharmaceuticals, including the usual therapuetic dose, method of administration, and indications for use and also describe about the pre-management checklists, and jndication/contraindication and follow-up protocol.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제28권2호
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• pp.95-110
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• 2006

The treatment for oral and maxillofacial carcinoma with chemotherapeutic agents is evaluated by many effective methods to reduce the tumor mass and cancer cell proliferation. However these chemotherapy have many serious side effects, such as bone marrow suppression, renal toxicity, G-I troubles. Therefore a possible approach to develop a clinically applicable chemotherapeutic agent is to screen anticancer activity of Taxol which is known to have very little side effect and have been used to breast cancer and ovarian carcinoma. Taxol is a new anti-microtubular anti-cancer agent extracted from the bark of the Pacific yew, Taxus brevifolia. Paclitaxel(Taxol) acts by promoting tubulin polymerization and over stabilizing microtubules agianst depolymerization. Despite the constant improvements of methods of the cancer treatment especially chemotherapy, the rate of cancer metastasis and recurrent are not decreased. Thus the investigation of new drug which have very little side effect and a possible clinically application continues to be a high priority. Considering that the Taxol have shown very effective chemotherapeutic agent with relatively low toxicity in many solid tumors, it deserves to evaluate its efficacy in oral squamous cell carcinoma. In this study, to investigate the in-vivo and in-vitro anti-cancer efficacy of Taxol in oral squamous cell carcinoma and lastly, the potency of Paclitaxel in the clinical application for oral cancer was evaluated. In vivo study, after HN22 cell line were xenografted in nude mice, the growth of tumor mass was observed, 3 mg/Kg taxol was injected intraperitoneally into nude mice containing tumor mass. The methods of these study were measurement of total volume of tumor mass, histopathologic study, immunohistochemical study, drug resistance assay, growth curve, MTT assay, flow cytometry, cDNA microarray in vivo and in vitro. The results were obtained as following. 1. The visual inspection of the experimental group showed that the volume of the tumor mass was slightly decreased but no significant difference with control group. 2. Ki-67 index was decreased at weeks 4 in experimental group. 3. Microscopic view of the xenografted tumor mass showed well differentiated squamous cell carcinoma and after Taxol injection, some necrotic tissue was seen weeks 4. 4. The growth curve of the tumor cells were decreased after 1day Taxol treatment. 5. According to the MTT assay, HN22 cell line showed relative drug resistancy above $5\;{\mu}g/ml$ concentrations of Taxol. 6. In drug resistance assay, the decrease of cell counts was seen relatively according to concentration. 7. In Flow cytometry, G2M phase cell arrests were seen in low concentration of the Taxol, while S phase cell arrests were seen in high concentration of the Taxol. 8. Using cDNA microarray technique, variable gene expression of ANGPTL4, TXNRD1, FAS, RRAGA, CTGF, CYCLINEA, P19, DUSP5, CEBPG, BTG1 were detacted in the oral squamous cell carcinoma cell after taxol treatment. In this study paclitaxel is effective against oral squamous cell carcinoma cell lines in vitro, but week effect was observed in vivo. So we need continuous study about anticancer effect of taxol in vivo in oral squamous cell carcinoma.

• 대한핵의학회지
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• 제34권4호
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• pp.303-311
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• 2000

목적: 생체 내에서 potassium과 유사한 역학을 보이는 thallium은 종양의 영상에 널리 사용된다. $K^+$ 통로개방제는 세포 내의 potassium을 외부로 배출되게 하는 기능이 있어 Tl-201을 이용한 종양영상에도 영향을 미칠 수 있을 것이라 생각된다. 본 연구는 강력한 $K^+$ 통로개방제의 하나인 pinacidil이 Tl-201을 이용한 종양의 국소화에 어떠한 영향을 미치는 가를 알아보기 위하여, 종양을 가진 생쥐에서 pinacidil에 의한 Tl-201의 체내분포 변화를 알아보았다. 대상 및 방법: 생쥐 유방암세포주를 이식받은 Balb/c 생쥐를 3주간 사육한 후 실험에 이용하였다. Tl-201 185 KBq를 꼬리정맥을 통해 주입한 후 일정시간에 실험동물을 희생시켜 Tl-201의 체내 분포를 알아 보았으며, pinacidil $100{\mu}g$ 투여에 따른 분포 변화를 알아보았다. 또한 Tl-201 3.7 MBq를 꼬리정맥을 통해 주입하여 Tl-201의 시간에 따른 전신 잔류율을 측정하였고, pinacidil 투여에 의한 전신 잔류율 변화를 구하였다. 결과: pinacidil 투여시 대조군에 비해 혈액 내 Tl-201의 방사능치를 약간 감소시키나 신장에서는 현저한 감소를 일으켰다. 또한 간, 근육, 및 장관의 방사능은 pinacidil 투여에 의해 변하지 않았다. 종양 내 Tl-201 섭취율 및 종양조직/혈액 무게당 섭취비는 대조군에 비해 pinacidil 투여군에서 낮았으며, Tl-201의 24시간 전신 잔류율도 pinacidil 투여군에서 낮았다. 결론: $K^+$ 통로개방제는 Tl-201의 체외 배설을 촉진시키고, 신장 섭취를 감소시켜나, 종양 섭취량도 감소시켰다. 그러므로 Tl-201 종양영상 판독시 $K^+$ 통로개방제를 사용하는 경우에는 오히려 Tl-201 종양영상의 질이 향상되기 보다는 저하될 수 있다는 사실을 고려하여야 할 것으로 생각된다.