• 제목/요약/키워드: differentiation therapy

검색결과 347건 처리시간 0.031초

HL6O 세포주의 분화 시 감소 특성을 보이는 Glutathione S-Transferase의 클로닝 (Cloning of a Glutathione S-Transferase Decreasing During Differentiation of HL60 Cell Line)

  • 김재철;박인규;이규보;손상균;김문규;김정철
    • Radiation Oncology Journal
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    • 제17권2호
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    • pp.151-157
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    • 1999
  • 목적 : HL60 세포주에서 PMA(phorbol 12-myrisate 13-acetate) 및 DMSO(dlmethyisulfoxlde) 에 의해 분화가 유도될 때 감소되는 특성을 보이는 K872 클론에 대한 염기 서열, 조직 분포, 단백 분리 등을 시행하였다. 재료 및 방법 QIA plasmid extraction kit(Qiagen GmbH, Germany)를 이용하여 사람의 모유두 세포 pBluescript phagemid cDNA library로부터 K872 클론을 추출하였다. Sanger's dideoxy nucleotide chain-termination method을 이용하여, 추출한 K872 클론의 염기 서열을 분석하였다. BLAST(Basic Local Alignment Search Tools) 프로그램으로 유전자은행의 염기 서열과의 상동성을 검색하였다. K872 클론으로 만든 probe로 다양한 인간 조직 및 암세포주로부터 분리한 RNA에 대하여 nothern blot을 시행하였다. His-Patch Thifusion expression system을 이용하여 대장균 배지에 0.1mM IPTG(Isopropyl-$\beta$-thlogalactopyranoslde) 를 첨가해서 결합단백의 유전자 발현을 유도하였다. 결합단백이 함유된 용출액을 SDS-PAGE에 걸어서 발현된 단백을 확인하였다. 결과 : K872 클론은 675개의 코딩 영역과 280개의 코딩과 관련없는 영역으로 구성된 1006개의 염기로 구성됨을 관찰하였다. 해독틀로 추정되는 부분은 시작 코돈을 포함하여 길6개의 아미노산을 형성하고 단백 산물의 분자량은 25,560 Da으로 추정되었다. 추정 아미노산 배열은 쥐의 glutathlone S-transferase kappa 1(rGSTKl) 의 아미노산 배열과 70$\%$의 상동성을 보였다. nothern blot에 따른 발현 양상은 심장, 수의근, 말초혈액 백혈구 등의 조직에서 높은 발현을 보였으며 방사선 내성과 관련지어 볼 때 대장암 및 흑색종 세포주에서 발현이 높았던 점은 특기할 만하였다. 결론 : 상동성 검색 결과 K872 유전자는 항암제 및 방사선 내성과 관련이 있는 rGSTK1에 대한 사람의 상동유전자로 사료되며 향후 이와 관련한 기능 분석이 필요할 것으로 사료된다

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노화와 요통에 따른 요추부 추간판 크기 변화 (The Change of Lumbar Intervertebral Disc Size on Aging and Low Back Pain)

  • 김종순;김창수
    • 대한방사선기술학회지:방사선기술과학
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    • 제30권4호
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    • pp.407-417
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    • 2007
  • 과거로부터 사회 경제학적인 문제로 주목을 받고 있는 요통은 노화와 유의한 관계가 있음이 보고되고 있으며, 이러한 노화에 의해 추간판의 여러 형태 조직학적 변화도 이미 여러 연구를 통해 보고되었으나 노화에 따른 추간판의 크기 변화에 대한 연구와 이러한 추간판의 변화가 요통과 관련이 있는지에 대한 연구는 거의 이루어지고 있지 않고 있는 실정이다. 이에 본 연구는 노화에 의한 추간판 변인의 변화를 알아보고, 이런 요인들이 정상 피검자와 요통 환자 사이에 차이가 있는지를 MRI 실계측에 의해 알아보고자 수행하였다. 본 연구는 근골격계 질환이 없는 20대$\sim$60대의 정상 성인 50명과 $20{\sim}60$대 요통 환자 50명을 대상으로 L4-5, L5-S1 추간판의 가로 직경, 세로 직경 그리고 면적을 MRI 영상을 통해 실계측하여 노화에 따른 변화와 정상 피검자와 요통 환자 사이의 차이를 비교하는 방식으로 진행하였다. 본 연구 결과 L4-5와 L5-S1 추간판의 가로 및 세로 직경, 면적은 노화에 의해 의미 있는 증가 경향을 보였으며 정상 피검자에 비해 요통 환자의 추간판 변인들이 큰 것을 확인하였다. 따라서 추간판의 크기 변화는 노화에 의한 자발적인 변화이며, 요통 환자의 추간판 변인 증가를 요통 진단에 참조할 수 있는 자료로 사용할 수 있을 것으로 사료되나, 차후 광범위한 피검자를 대상으로 하는 보다 폭넓고 다각적인 연구가 필요한 것으로 사료된다.

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Potential Therapeutic Targets for the Primary Gallbladder Carcinoma: Estrogen Receptors

  • Zhang, Ling-Qiang;Zhang, Xiu-De;Xu, Jia;Wan, Yong;Qu, Kai;Zhang, Jing-Yao;Wang, Zhi-Xin;Wei, Ji-Chao;Meng, Fan-Di;Tai, Ming-Hui;Zhou, Lei;Liu, Chang
    • Asian Pacific Journal of Cancer Prevention
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    • 제14권4호
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    • pp.2185-2190
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    • 2013
  • Gallbladder carcinoma, the most frequent malignant neoplasm of the biliary tract system, has always been considered to feature late clinical presentation and diagnosis, limited treatment options and an extremely poor prognosis. In recent years, while the incidence of gallbladder cancer has appeared to be on the increase, the available treatment methods have not greatly improved survival of the affected patients. Thus, exploring new therapeutic targets for this devastating disease is an urgent matter at present. Epidemical studies have demonstrated that the incidence of gallbladder carcinoma exhibits a distinct gender bias, affecting females two to three times more than males, pointing to crucial roles of estrogen. It is well known that estrogen acts on target tissues by binding to estrogen receptors (ERs), which are mainly divided into three subtypes, $ER{\alpha}$, $ER{\beta}$ and $ER{\gamma}$. $ER{\alpha}$ and $ER{\beta}$ appear to have overlapping but also unique even opposite biological effects. As important pathogenic mediators, ERs have been considered to relate to several kinds of tumors. In gallbladder carcinoma tissue, ERs have been shown to be positively expressed, and ERs expression levels are associated with differentiation and prognosis of this cancer. Nevertheless, the exact mechanisms of estrogen inducing growth of gallbladder carcinoma remain poorly understood. On the base of the current investigations, we deduce that estrogen participates in promotion of gallbladder carcinoma by influencing the formation of gallstones, stimulating angiogenesis, and promoting abnormal proliferation. Since ERs mediate the carcinogenic actions of estrogen in gallbladder, and therapy targeting ERs may provide new directions for gallbladder carcinoma. Therefore, it should be stressed that ERs are potential therapeutic targets for gallbladder carcinoma.

Anti-tumor Activity and Apoptosis-regulation Mechanisms of Bufalin in Various Cancers: New Hope for Cancer Patients

  • Yin, Pei-Hao;Liu, Xuan;Qiu, Yan-Yan;Cai, Jian-Feng;Qin, Jian-Min;Zhu, Hui-Rong;Li, Qi
    • Asian Pacific Journal of Cancer Prevention
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    • 제13권11호
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    • pp.5339-5343
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    • 2012
  • The induction of apoptosis in target cells is a key mechanism for most anti-tumor therapies. Bufalin is a cardiotonic steroid that has the potential to induce differentiation and apoptosis of tumor cells. Research on bufalin has so far mainly involved leukemia, prostate cancer, gastric cancer and liver cancer, and has been confined to in vitro studies. The bufadienolides bufalin and cinobufagin have been shown to induce apoptosis in a wide spectrum of cancer cell. The present article reviews the anticancer effects of bufalin. It induces apoptosis of lung cancer cells via the PI3K/Akt pathway and also suppressed the proliferation of human non-small cell lung cancer A549 cell line in a time and dose dependent manner. Bufalin, bufotalin and gamabufotalin, key bufadienolides, significantly sensitize human breast cancer cells with differing ER-alpha status to apoptosis induction by the TNF-related apoptosis-inducing ligand (TRAIL). In addition, bufadienolides induce prostate cancer cell apoptosis more significantly than that in breast epithelial cell lines. Similar effects have been observed with hepatocellular carcinoma (HCC) but the detailed molecular mechanisms of inducing apoptosis in this case are still unclear. Bufalin exerts profound effects on leukemia therapy in vitro. Results of multiple studies indicate that bufalin has marked anti-tumor activities through its ability to induce apoptosis. Large-scale randomized, double-blind, placebo or positive drug parallel controlled studies are now required to confirm the efficacy and apoptosis-inducing potential of bufalin in various cancers in the cliniucal setting.

Biological effects of a semiconductor diode laser on human periodontal ligament fibroblasts

  • Choi, Eun-Jeong;Yim, Ju-Young;Koo, Ki-Tae;Seol, Yang-Jo;Lee, Yong-Moo;Ku, Young;Rhyu, In-Chul;Chung, Chong-Pyoung;Kim, Tae-Il
    • Journal of Periodontal and Implant Science
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    • 제40권3호
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    • pp.105-110
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    • 2010
  • Purpose: It has been reported that low-level semiconductor diode lasers could enhance the wound healing process. The periodontal ligament is crucial for maintaining the tooth and surrounding tissues in periodontal wound healing. While low-level semiconductor diode lasers have been used in low-level laser therapy, there have been few reports on their effects on periodontal ligament fibroblasts (PDLFs). We performed this study to investigate the biological effects of semiconductor diode lasers on human PDLFs. Methods: Human PDLFs were cultured and irradiated with a gallium-aluminum-arsenate (GaAlAs) semiconductor diode laser of which the wavelength was 810 nm. The power output was fixed at 500 mW in the continuous wave mode with various energy fluencies, which were 1.97, 3.94, and 5.91 $J/cm^2$. A culture of PDLFs without laser irradiation was regarded as a control. Then, cells were additionally incubated in 72 hours for MTS assay and an alkaline phosphatase (ALPase) activity test. At 48 hours post-laser irradiation, western blot analysis was performed to determine extracellular signal-regulated kinase (ERK) activity. ANOVA was used to assess the significance level of the differences among groups (P<0.05). Results: At all energy fluencies of laser irradiation, PDLFs proliferation gradually increased for 72 hours without any significant differences compared with the control over the entire period taken together. However, an increment of cell proliferation significantly greater than in the control occurred between 24 and 48 hours at laser irradiation settings of 1.97 and 3.94 $J/cm^2$ (P<0.05). The highest ALPase activity was found at 48 and 72 hours post-laser irradiation with 3.94 $J/cm^2$ energy fluency (P<0.05). The phosphorylated ERK level was more prominent at 3.94 $J/cm^2$ energy fluency than in the control. Conclusions: The present study demonstrated that the GaAlAs semiconductor diode laser promoted proliferation and differentiation of human PDLFs.

위암 조직내 Metallothionein의 면역 세포화학적 연구 (Immunocytochemical Localization of Metallothionein in Gastric Adenocarcinoma)

  • 양승하;신길상;김완종
    • Applied Microscopy
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    • 제32권4호
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    • pp.411-419
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    • 2002
  • 사람의 위암 조직을 미세구조와 metallothionein (MT)에 대한 면역 조직 및 세포화학적 방법으로 조사하였던 바, 다음과 같은 결과를 얻어냈다. 위암 세포들은 핵 세포질비가 정상세포에 비해 크고, 불규칙한 핵과 이질염색질의 분포가 증가하였으며, 세포질내에서 유리리보솜의 분포가 뚜렷이 증가하였다. 면역 조직 및 세포화학적 방법으로 MT의 발현을 조사하였던 결과, 이 단백질은 위암조직의 암세포에서 반응성이 높게 나타났으며, 주로 핵 부위에 집중되는 경향을 보였으며, 특히 이질염색질과 인 부위에서 면역 금입자들이 주로 분포하는 것으로 관찰되었다. 이러한 결과들은 위암 세포의 미세구조가 미분화세포들이 나타내는 일반적인 특징과 비교되었으며, 위암 세포에서 MT가 증가하는 현상은 이 단백질이 세포질에서 합성되어 핵내로 수송된 후, 세포 증식을 위한 전사과정에 관여할 것임을 시사하는 것이다.

제대혈 유래 중간엽줄기세포에서 HLA의 발현과 Mixed Lymphocyte Reaction (Expression of HLA and Mixed Lymphocyte Reaction of Mesenchymal Stem Cells Derived from Human Umbilical Cord Blood)

  • 이효종;강선영;박세진;이승용;이희천;고필옥;박지권;백원영;연성찬
    • 한국임상수의학회지
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    • 제28권4호
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    • pp.399-402
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    • 2011
  • In recent years, the mesenchymal stem cells (MSC) derived from various tissues have been widely tested for developing cell therapies, tissue repair and transplantation. Although there has been much interest in the immunomodulatory properties of MSC and their immunologic reactions following autologous, allogeneic and xenogenic transplantation of MSC in vivo, up to date, the expression of immunogenic markers, such as class I and II human leukocyte antigens (HLA), after differentiation of human umbilical cord blood (hUCB)-derived MSC has been poorly investigated and require extensive in vitro and in vivo testing. In this experiment, the expression of the HLA-ABC and HLA-DR on hUCB-derived MSC have been tested by immunocytochemical staining. The undifferentiated MSC were moderately stained for HLA-ABC but very weakly for HLA-DR. In order to investigate the inhibitory effect of allogeneic lymphocytes on proliferation of MSC, the MSC were cultured in the presence or absence of peripheral allogeneic lymphocytes stimulated with concanavalin A. The allogeneic lymphocytes did not significantly inhibit MSC proliferation. We conclude that hUCB-MSC expressed moderately class I HLA antigen while almost negatively class II HLA antigen. The MSC have an immunomodulatory effect which can suppress the allogeneic response of lymphocytes. These in vitro data suggest that allogeneic MSC derived from cord blood can be useful candidate for allogeneic cell therapy and transplantation without a major risk of rejection.

신체계측 추정식과 의료영상 실계측 방법의 요추부 추간판 크기 비교 (Comparison of Anthropometric Method & Medical Image Method in the Lumbar Intervertebral Disc Size)

  • 김종순;김창수
    • 대한방사선기술학회지:방사선기술과학
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    • 제30권2호
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    • pp.121-127
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    • 2007
  • 최근 요통의 원인을 밝히기 위한 노력의 일환으로 의료 영상 자료를 이용하는 연구가 많이 이루어지고 있는 실정이나 의료 영상 장비들은 사용 비용이 고가라는 점, 인체에 침습적이라는 점 그리고 추간판의 크기를 측정하기 위해서는 이를 구현할 수 있는 소프트웨어가 필요하다는 점 등의 제한점으로 인해 연구 환경에서는 그 사용이 제한적으로 이루어지고 있는 실정이다. 이에 본 연구는 비교적 신뢰도가 높으면서 신체 계측 자료를 이용하여 간단한 추정식에 의해 추간판의 크기를 추정할 수 있는 Colombini 등의 방법과 이를 수정하여 보다 발전시킨 Turk와 Celan의 방법을 소개하고 이들의 방법에 의해 추정된 추간판의 크기가 의료 영상 자료에 의한 실계측치와 유의한 상관성이 있는가를 알아보기 위하여 수행되었다. 본 연구는 근골격계 질환이 없는 20대의 정상 성인을 대상으로 신체 계측을 통해 구해진 자료를 Colombi의 추정식과 Turk와 Celan의 추정식으로 처리한 후 이를 통해 구해진 L4-5, L5-S1 추간판의 크기를 CT 영상을 통해 구해진 실계측치와 비교하는 방식으로 진행되었다. 본 연구 결과 L4-5와 L5-S1 추간판의 크기는 Colombi 추정식에 의해 구해진 값이 Turk와 Celan 추정식으로 구한 값이나 CT 영상을 통해 얻어진 실계측치 보다 약간 큰 것으로 나타났으나 Turk와 Celan의 값과 CT에 의한 실계측치 사이에는 유의한 차이가 없었다. 따라서 신체 계측을 통한 추간판 크기의 추정 방법인 Turk와 Celan의 공식이 CT 실계측과 매우 높은 상관성을 가진다는 것을 알 수 있었다.

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Pleiotrophin이 골수 줄기 세포의 부착 및 골형성에 미치는 효과에 대한 연구 (PLEIOTROPHIN EFFECTS ON BINDING AND SUBSEQUENT OSTEOGENESIS OF HUMAN MESENCHYMAL STEM CELLS)

  • 윤정호;윤정주;장현석;임재석;이의석;김대성;권종진
    • Maxillofacial Plastic and Reconstructive Surgery
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    • 제28권2호
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    • pp.111-117
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    • 2006
  • An area of current research is investigating the app1ication of human mesenchymal stem cells or hMSCs as a cell-based regenerative therapy. In order to achieve effective bone regeneration, appropriate matrices functioning as cell-carriers must be identified and optimized in terms of function, efficacy and biocompatibility. Two methods of approaching optimization of matrices are to facilitate adhesion of the donor hMSCs and furthermore to facilitate recruitment of host progenitor cells to osteoblastic differentiation. Pleiotrophin is an extracellular matrix protein that was first identified in developing rat brains and believed to be associated with developing neuronal pathways. A recent publication by Imai and colleagues demonstrated that transgenic mice with upregulated pleiotrophin expression developed a greater volume of cortical as well as cancellous bone. The proposed mechanism of action of pleiotrophin is demonstrated here. Through either environmental stresses and/or intracellular regulation, there is an increase in pleiotrophin production. The pleiotrophin is released extracellularly into areas requiring bone deposition. A receptor-mediated process recruits host osteoprogenitor cells into these areas. Therefore, the aim of our study was to investigate the osteoconductive properties of pleiotrophin. We wanted to determine if pleiotrophin coating facilitates cellular adhesion and furthermore if this has any effect on hMSCs derived bone formation in an animal model. The results showed a dose dependent response of cellular adhesion in fibronectin samples, and cellular adhesion was facilitated with increasing pleiotrophin concentrations. Histologic findings taken after 5 weeks implantation in SCID mouse showed no presence of bone formation with only a dense fibrous connective tissue. Possible explanations for the results of the osteogenesis assay include inappropriate cell loading.

Preoperative N Staging of Gastric Cancer by Stomach Protocol Computed Tomography

  • Kim, Se Hoon;Kim, Jeong Jae;Lee, Jeong Sub;Kim, Seung Hyoung;Kim, Bong Soo;Maeng, Young Hee;Hyun, Chang Lim;Kim, Min Jeong;Jeong, In Ho
    • Journal of Gastric Cancer
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    • 제13권3호
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    • pp.149-156
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    • 2013
  • Purpose: Clinical stage of gastric cancer is currently assessed by computed tomography. Accurate clinical staging is important for the tailoring of therapy. This study evaluated the accuracy of clinical N staging using stomach protocol computed tomography. Materials and Methods: Between March 2004 and November 2012, 171 patients with gastric cancer underwent preoperative stomach protocol computed tomography (Jeju National University Hospital; Jeju, Korea). Their demographic and clinical characteristics were reviewed retrospectively. Two radiologists evaluated cN staging using axial and coronal computed tomography images, and cN stage was matched with pathologic results. The diagnostic accuracy of stomach protocol computed tomography for clinical N staging and clinical characteristics associated with diagnostic accuracy were evaluated. Results: The overall accuracy of stomach protocol computed tomography for cN staging was 63.2%. Computed tomography images of slice thickness 3.0 mm had a sensitivity of 60.0%; a specificity of 89.6%; an accuracy of 78.4%; and a positive predictive value of 78.0% in detecting lymph node metastases. Underestimation of cN stage was associated with larger tumor size (P<0.001), undifferentiated type (P=0.003), diffuse type (P=0.020), more advanced pathologic stage (P<0.001), and larger numbers of harvested and metastatic lymph nodes (P<0.001 each). Tumor differentiation was an independent factor affecting underestimation by computed tomography (P=0.045). Conclusions: Computed tomography with a size criterion of 8 mm is highly specific but relatively insensitive in detecting nodal metastases. Physicians should keep in mind that computed tomography may not be an appropriate tool to detect nodal metastases for choosing appropriate treatment.