• 제목/요약/키워드: Bone surface tumor

검색결과 46건 처리시간 0.035초

마우스세포를 이용한 홍삼추출물과 생약복합추출물의 병용 처리에 따른 면역활성 효과 (Immunological Synergistic Effects of Combined Treatment with Herbal Preparation (HemoHIM) and Red Ginseng Extracts)

  • 변명우;변의홍
    • 한국식품영양과학회지
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    • 제44권2호
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    • pp.182-190
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    • 2015
  • 본 연구는 홍삼추출물(홍삼단)과 생약복합추출물(헤모힘)이 주요 기능성분은 다르지만 면역활성이라는 생리활성 측면에서 동일한 효과를 인정하고 있어서 이들의 병용 처리가 면역세포에 어떠한 영향을 미치는지에 대해 알아보기 위하여 수행되었다. 면역활성능에 관한 평가를 진행하기 위하여 마우스의 골수에서 분리한 미분화 골수세포를 선천면역에서 중요한 역할을 수행하는 대식세포 및 수지상세포로 분화시킨 후 홍삼추출물과 생약복합추출물을 병용 처리하였을 때 대식세포 및 수지상세포의 세포 증식능 및 사이토카인의 분비능이 증가되는 것으로 관찰되었다. 또한 활성화된 탐식(면역)세포의 세포 표면에서 발현되는 CD80과 CD86의 발현과 탐식(면역)세포의 항원제시에 밀접한 관련이 있는 주 조직적합성 복합체(MHC class II)의 발현이 홍삼추출물과 생약복합추출물의 병용 처리구에서 유의적으로 증가되는 것으로 관찰되었다. 또한 후천면역에서 중요한 역할을 수행하는 면역 T 세포가 다량으로 분포하는 비장 조직으로부터 비장세포를 분리하여 홍삼추출물과 생약복합추출물을 병용처리하였을 때 세포 증식능 및 면역활성을 유도하는 Th1 세포가 분비하는 사이토카인의 함량이 증가되는 것으로 나타났다. 이러한 결과로 미루어 볼 때 홍삼추출물과 생약복합 추출물의 병용 처리는 선천면역뿐만 아니라 후천면역에 관여하는 다양한 면역세포의 활성화에 직 간접적으로 다양한 상승작용을 미치는 것으로 사료된다.

항종양 면역반응 유도를 위한 수지상세포의 최적 활성화 조건 (The Optimal Activation State of Dendritic Cells for the Induction of Antitumor Immunity)

  • 남병혁;조월순;이기원;오수정;강은영;최유진;도은주;홍숙희;임영진;김기욱;정민호
    • 생명과학회지
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    • 제16권6호
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    • pp.904-910
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    • 2006
  • 수지상세포는 종양면역에서 필수적인 강력한 CTL 반응을 개시할 수 있는 유일한 세포이다 . 특히 외인성 종양항원에 대한 CTL 반응 유도는 활성화된 수지상세포의 IL-12 분비를 통한 CD4+ helper T세포의 cross-priming을 필요로 한다. 그러나 최근에 활성화된 수지상세포는 $Th_1$ 면역반응을 유도하지만 활성화 시간이 경과함에 따라 오히려 $Th_2$반응을 유도 할 수 있다. 따라서 본 연구에서는 OVA를 종양항원 모델로 설정하여 종양특이적인 CTL 반응을 형성하기 위한 최적의 수지상세포 활성화 조건을 조사하였다. 마우스 골수세포에 서 수지상세포로의 분화는 항원제시 기능을 위한 표면분자의 발현 측면에서 볼 때 배양 6일-7일 정도가 적합하였다. 수지상세포의 IL-12 생성능은 배양 6일 이상, OVA 항원 탑재 8시간 이상의 경우에 연이은 LPS 성숙자극으로 오히려 감소하는 경향을 보였다. 즉 배양 6일의 수지상세포에 OVA 항원 탑재를 8시간 수행한 경우(8-h DC)가 in vitro에서의 IL-12생성능, ex vivo에서의 세포내 $IFN-{\gamma}$를 발현하는 CD8+ T세포의 증가 및 OVA 특이적인 세포독성효과 등에서 가장 좋은 결과를 보였다. 또한 in vivo에서 종양 치료 및 예방효과에서도 8-h DC로 면역한 경우에 가장 우수한 종양형성 억제 효과와 생존기간 연장효과를 보였다. 현재 대부분의 수지상 세포를 이용한 항종양 백신에서 항원 탑재반응을 24시간 동안 수행하고 있으나, 본 실험의 결과로 볼 때, 8시간의 in vitro 항원 탑재가 보다 효과적인 종양특이적 CTL 반응과 항종양 면역반응을 유도함을 알 수 있다. 결론적으로 본 연구를 통하여 8시간 이상의 항원접촉은 수지상세포의 기능적 활성능력을 오히려 고갈시킬 수 있음을 제시한다.

Stem Cell Biology, 최근의 진보 (Recent Advancement in the Stem Cell Biology)

  • 한창열
    • Journal of Plant Biotechnology
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    • 제33권3호
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    • pp.195-207
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    • 2006
  • Stem cells are the primordial, initial cells which usually divide asymmetrically giving rise to on the one hand self-renewals and on the other hand progenitor cells with potential for differentiation. Zygote (fertilized egg), with totipotency, deserves the top-ranking stem cell - he totipotent stem cell (TSC). Both the ICM (inner cell mass) taken from the 6 days-old human blastocyst and ESC (embryonic stem cell) derived from the in vitro cultured ICM have slightly less potency for differentiation than the zygote, and are termed pluripotent stem cells. Stem cells in the tissues and organs of fetus, infant, and adult have highly reduced potency and committed to produce only progenitor cells for particular tissues. These tissue-specific stem cells are called multipotent stem cells. These tissue-specific/committed multipotent stem cells, when placed in altered environment other than their original niche, can yield cells characteristic of the altered environment. These findings are certainly of potential interest from the clinical, therapeutic perspective. The controversial terminology 'somatic stem cell plasticity' coined by the stem cell community seems to have been proved true. Followings are some of the recent knowledges related to the stem cell. Just as the tissues of our body have their own multipotent stem cells, cancerous tumor has undifferentiated cells known as cancer stem cell (CSC). Each time CSC cleaves, it makes two daughter cells with different fate. One is endowed with immortality, the remarkable ability to divide indefinitely, while the other progeny cell divides occasionally but lives forever. In the cancer tumor, CSC is minority being as few as 3-5% of the tumor mass but it is the culprit behind the tumor-malignancy, metastasis, and recurrence of cancer. CSC is like a master print. As long as the original exists, copies can be made and the disease can persist. If the CSC is destroyed, cancer tumor can't grow. In the decades-long cancer therapy, efforts were focused on the reducing of the bulk of cancerous growth. How cancer therapy is changing to destroy the origin of tumor, the CSC. The next generation of treatments should be to recognize and target the root cause of cancerous growth, the CSC, rather than the reducing of the bulk of tumor, Now the strategy is to find a way to identify and isolate the stem cells. The surfaces of normal as well as the cancer stem cells are studded with proteins. In leukaemia stem cell, for example, protein CD 34 is identified. In the new treatment of cancer disease it is needed to look for protein unique to the CSC. Blocking the stem cell's source of nutrients might be another effective strategy. The mystery of sternness of stem cells has begun to be deciphered. ESC can replicate indefinitely and yet retains the potential to turn into any kind of differentiated cells. Polycomb group protein such as Suz 12 repress most of the regulatory genes which, activated, are turned to be developmental genes. These protein molecules keep the ESC in an undifferentiated state. Many of the regulator genes silenced by polycomb proteins are also occupied by such ESC transcription factors as Oct 4, Sox 2, and Nanog. Both polycomb and transcription factor proteins seem to cooperate to keep the ESC in an undifferentiated state, pluripotent, and self-renewable. A normal prion protein (PrP) is found throughout the body from blood to the brain. Prion diseases such as mad cow disease (bovine spongiform encephalopathy) are caused when a normal prion protein misfolds to give rise to PrP$^{SC}$ and assault brain tissue. Why has human body kept such a deadly and enigmatic protein? Although our body has preserved the prion protein, prion diseases are of rare occurrence. Deadly prion diseases have been intensively studied, but normal prion problems are not. Very few facts on the benefit of prion proteins have been known so far. It was found that PrP was hugely expressed on the stem cell surface of bone marrow and on the cells of neural progenitor, PrP seems to have some function in cell maturation and facilitate the division of stem cells and their self-renewal. PrP also might help guide the decision of neural progenitor cell to become a neuron.

악성흑색종 환자군에서 수술적 치료 후 시행한 고용량 인터페론-${\alpha}2b$ 면역요법에 의한 보조적 치료 결과 분석: 예비보고 (The Analysis of Post Operative Treatment of Malignant Melanoma Using High Dose Interferon-${\alpha}2b$ Immunotherapy: Preliminary Report)

  • 정소학;조현익
    • 대한골관절종양학회지
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    • 제18권2호
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    • pp.78-82
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    • 2012
  • 목적: 고용량 인터페론-${\alpha}2b$를 이용한 악성흑색종의 면역요법은 외과적 절제술 후 현미경적 적이나 남아있는 종양의 재발을 막고 무병생존율과 전체 생존율을 높이는 것으로 알려져 있다. 저자 등은 악성 흑색종 환자군에서 외과적 절제술 후 고용량 인터페론-${\alpha}$ 면역요법을 시행한 그룹의 무병생존기간 및 전체 생존율 등을 비교 분석하여 면역요법의 치료결과를 예비 보고하고자 한다. 대상 및 방법: 2010년 2월부터 2012년 10월까지 본원에서 악성 흑색종으로 진단받고 외과적 수술 후 면역치료를 시행한 5명을 대상으로 분석 하였다. 병기는 AJCC 병기를 이용하여 판정하였으며 IIA 3예, IIB 1예, IV 1예로 나타났다. 추시기간은 최소 7개월에서 최대 32개월이었다. 면역 요법을 시행한 군에서는 먼저 유도요법으로 ${\alpha}2b$를 체표면적 당 20만 IU를 총 4주간 1주일에 5회 정주하였으며 이후 유지요법으로 체표면적당 10만 IU를 총 48주간 1주일에 3회 피하주사하였다. 이들 환자들에 대해 국소재발과 국소전이, 그리고 원격전이여부를 조사하였고 무병생존기간을 조사하였다. 결과: 인터페론-${\alpha}2b$ 면역요법을 시행한 환자군에서 추시 흉부 전산화 단층촬영 및 양전자 컴퓨터 단층촬영을 통한 평가 결과 현재까지 모두 국소 재발 및 국소전이 원격전이의 증거가 없는 것으로 나타났다. 결론: 고용량 인터페론-${\alpha}$ 면역요법 시행군에서 현재까지 종양의 국소 재발 및 전이를 막는 것으로 나타났으나 향후 궁극적인 생존율 및 무병생존율 향상이 달성되는가에 대해서는 추가적인 연구대상과 추적관찰이 필요하겠다.

Cytotoxic T Lymphocytes Elicited by Dendritic Cell-Targeted Delivery of Human Papillomavirus Type-16 E6/E7 Fusion Gene Exert Lethal Effects on CaSki Cells

  • Wu, Xiang-Mei;Liu, Xing;Jiao, Qing-Fang;Fu, Shao-Yue;Bu, You-Quan;Song, Fang-Zhou;Yi, Fa-Ping
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권6호
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    • pp.2447-2451
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    • 2014
  • Human papillomavirus (HPV) is the primary etiologic agent of cervical cancer. Consideration of safety and non human leukocyte antigen restriction, protein vaccine has become the most likely form of HPV therapeutic vaccine, although none have so far been reported as effective. Since tumor cells consistently express the two proteins E6 and E7, most therapeutic vaccines target one or both of them. In this study, we fabricated DC vaccines by transducing replication-defective recombinant adenoviruses expressing E6/E7 fusion gene of HPV-16, to investigate the lethal effects of specific cytotoxic T lymphocytes (CTL) against CaSki cells in vitro. Mouse immature dendritic cells (DC) were generated from bone marrow, and transfected with pAd-E6/E7 to prepare a DC vaccine and to induce specific CTL. The surface expression of CD40, CD68, MHC II and CD11c was assessed by flow cytometry (FCM), and the lethal effects of CTL against CaSki cells were determined by DAPI, FCM and CCK-8 methods. Immature mouse DC was successfully transfected by pAd-E6/E7 in vitro, and the transfecting efficiency was 40%-50%. A DC vaccine was successfully prepared and was used to induce specific CTL. Experimental results showed that the percentage of apoptosis and killing rate of CaSki cells were significantly increased by coculturing with the specific CTL (p <0.05). These results illustrated that a DC vaccine modified by HPV-16 E6/E7 gene can induce apoptosis of CaSki cells by inducing CTL, which may be used as a new strategy for biological treatment of cervical cancer.

Subcutaneous Streptococcus dysgalactiae GAPDH vaccine in mice induces a proficient innate immune response

  • Ran An;Yongli Guo;Mingchun Gao;Junwei Wang
    • Journal of Veterinary Science
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    • 제24권5호
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    • pp.72.1-72.16
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    • 2023
  • Background: Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) on the surface of Streptococcus dysgalactiae, coded with gapC, is a glycolytic enzyme that was reported to be a moonlighting protein and virulence factor. Objective: This study assessed GAPDH as a potential immunization candidate protein to prevent streptococcus infections. Methods: Mice were vaccinated subcutaneously with recombinant GAPDH and challenged with S. dysgalactiae in vivo. They were then evaluated using histological methods. rGAPDH of mouse bone marrow-derived dendritic cells (BMDCs) was evaluated using immunoblotting, reverse transcription quantitative polymerase chain reaction, and enzyme-linked immunosorbent assay methods. Results: Vaccination with rGAPDH improved the survival rates and decreased the bacterial burdens in the mammary glands compared to the control group. The mechanism by which rGAPDH vaccination protects against S. dysgalactiae was investigated. In vitro experiments showed that rGAPDH boosted the generation of interleukin-10 and tumor necrosis factor-α. Treatment of BMDCs with TAK-242, a toll-like receptor 4 inhibitor, or C29, a toll-like receptor 2 inhibitor, reduced cytokines substantially, suggesting that rGAPDH may be a potential ligand for both TLR2 and TLR4. Subsequent investigations showed that rGAPDH may activate the phosphorylation of MAPKs and nuclear factor-κB. Conclusions: GAPDH is a promising immunization candidate protein for targeting virulence and enhancing immune-mediated protection. Further investigations are warranted to understand the mechanisms underlying the activation of BMDCs by rGAPDH in a TLR2- and TLR4-dependent manner and the regulation of inflammatory cytokines contributing to mastitis pathogenesis.

골수강내 혈관성 근피판 이식이 동결 건조후 자가 이식된 관절연골의 재생에 미치는 효과 (Effects of Intramedullary Vascularized Muscle Flap in Regeneration of Lyophilized, Autografted Humeral Head in Rabbits)

  • 이승구;김성태;박진일
    • Archives of Reconstructive Microsurgery
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    • 제9권2호
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    • pp.139-146
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    • 2000
  • The aim of this study was to assess whether the functional regeneration of a lyophilized autografted cartilage could be improved by implanting a vascularized muscle flap into the medullary canal of autografted proximal humerus. A hemijoint reconstruction using a lyophilized osteochondral autograft in proximal humerus was done in 4 rabbits for control, and combined with an vascularized intramedullary muscle flap in another 4 rabbits for the experimental group. Graft healing and the repair process of osteochondral graft were followed by serial radiographs and histologic changes for 9 weeks after experiments. Each two rabbits in control and in experimental group on 5th and 9th week after implantation of hemijoint were sacrified. The results were as follows: 1. All of control and experimental froups on 5th week united solidly on osteotomized site radiologically, but their articular cartilages were destroyed more seriously in the control than that in experimental group with muscle flap on 5th and 9th week after experiment... 2. Histochemically, the cartilage surface are completely destroyed and revealed with severe osteoarthritic changes on all cartilage layers in control, but cartilaginous erosions are mild to moderate and their arthritic changes are also mild with somewhat regeneration of chondrocytes on deep layers more prominetly on 9th week of the experimental group. 3. The amount of collagen and protenized matrix which was determined by Masson-Trichrome stain was markedly decreased that means the weakness of bony strength and low osteogenic potential in lyophilized cartilage. These results suggest that an intramedullary vascularized muscle flap can improve the functional results of lyophilized osteochondral autograft by providing both increased vascularity and populations of mesenchymal cells to initiate new bone formation on osteotomized site as well as the regeneration of deep layers in articular cartilage. In clinical relevances, this lyophilized hemijoint autograft combined with an intramedullary vascularized muscle pedicle graft might be used very effectively for the treatment of malignant long bone tumors to preserve the joint functions, all or partly, and so to replace it with the artificial joint after tumor excision and hemijoint autograft.

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법랑모세포 섬유종에 의한 하악 제1대구치의 맹출지연 (DELAYED ERUPTION OF LOWER FIRST MOLAR ASSOCIATED WITH AMELOBLASTIC FIBROMA)

  • 정정화;김영진;김현정;남순현
    • 대한소아치과학회지
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    • 제38권3호
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    • pp.262-269
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    • 2011
  • 법랑모세포 섬유종은 드문 진성의 혼합성 양성종양으로 20세 이하의 비교적 어린 연령층의 하악 후방부에 호발한다. 흔히 하악 구치부의 미맹출치와 관련하여 발생하며 치조골 표면에서 서서히 성장하여 이환치를 치근단 방향으로 변위시켜 정상적인 치아 맹출을 방해한다. 약간의 피질골 팽창 외에 다른 증상은 거의 없어서 정기적인 방사선학적 평가에서 우연히 발견되는 경우가 많다. 임상적 및 방사선학적으로 법랑모세포 섬유치아종 및 치아종과 비슷하나 조직학적으로 치아 경조직의 형성이 관찰되지 않는 것이 다르다. 치료방법은 적출술과 주위 골의 소파술을 포함한 보존적 외과적 처치가 일반적이나 재발가능성이 있고 악성종양으로의 변이를 보인다는 일부 보고가 있어 절제술과 같은 보다 공격적인 치료방법이 추천되기도 한다. 하지만 대부분의 병소는 피막으로 잘 둘러싸여 있으며 주변의 골와에서 쉽게 분리되므로 재발률은 낮은 편이다. 본 증례는 하악 좌측 제1대구치의 맹출지연과 관련된 법랑모세포 섬유종을 주소로 본과에 내원한 환아들을 대상으로 보존적인 적출술 및 소파술을 시행한 것으로 정기적인 관찰 결과 비교적 양호한 제1대구치의 자연적 맹출양상을 보여 보고하는 바이다.

자소엽(Perilla frutescens Britton var. acuta Kudo) 조다당류 추출물의 면역활성 효과 (Immunomodulatory activities of crude polysaccharide fraction separated from Perilla frutescens Britton var. acuta Kudo)

  • 변의홍
    • 한국식품과학회지
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    • 제49권5호
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    • pp.559-566
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    • 2017
  • 본 연구는 자소엽 조다당 추출물(PCP)의 면역활성에 관하여 알아보기 위하여, 선천면역계의 대표적인 면역세포인 수지상세포 및 후천면역계의 대표적인 면역세포인 비장세포에 PCP를 처리하여 면역세포의 면역활성능에 관하여 측정하였다. 수지상세포에 PCP를 1, 5 및 $10{\mu}g/mL$의 농도를 처리한 결과, 세포생존율이 $103.4{\pm}3.8$, $108.8{\pm}2.1$, $117.8{\pm}3.3%$ (n =3)로 나타나 세포독성을 유발하지 않았으며, 주요 면역활성 인자인 산화질소의 분비능을 관찰한 결과, 각각 $2.7{\pm}0.2$, $4.5{\pm}0.2$, $7.3{\pm}0.3{\mu}M$ (n =3)로 농도 의존적으로 나타났다. 농도(1, 5 및 $10{\mu}g/mL$)별 PCP 처리구에서 사이토카인의 분비능을 관찰한 결과, TNF-${\alpha}$ ($372.3{\pm}0.32$, $604.8{\pm}0.54$$954.2{\pm}1.32pg/mL$), IL-6 ($508.4{\pm}0.39$, $761.5{\pm}1.34$$1038.5{\pm}1.67pg/mL$), IL-$1{\beta}$ ($314.5{\pm}1.04$, $524.8{\pm}1.89$$664.8{\pm}0.89pg/mL$), IL-12 ($321.4{\pm}0.94$, $832.5{\pm}0.85$$901.{\pm}0.94pg/mL$)가 유의적으로 증가되는 것으로 관찰되었다. 또한 후천면역에서 중요한 역할을 수행하는 면역 T 세포가 다량으로 분포하는 비장 조직으로부터 비장세포를 분리하여 PCP를 처리하였을 때, 세포 증식능이 유의적으로 증가하였으며, 면역활성을 유도하는 Th1 세포가 분비하는 사이토카인의 함량 또한 유의적으로 증가되는 것으로 나타났다. 이러한 결과로 미루어 볼 때 PCP의 처리는 선천면역뿐만 아니라 후천면역에 관여하는 다양한 면역세포의 활성화에 직간접적으로 관여하는 것으로 사료된다. 본 연구는 자소엽조다당 추출물의 면역활성 유도 효과에 관한 가능성을 제시하였고, 향후 자소엽 조다당 추출물을 분리 및 정제과정을 통하여 구조분석 및 정제된 조다당 추출물의 정확한 면역활성과 면역활성기전에 관한 면밀한 연구가 필요할 것으로 사료된다.

Treatment outcomes after adjuvant radiotherapy following surgery for patients with stage I endometrial cancer

  • Kim, Jiyoung;Lee, Kyung-Ja;Park, Kyung-Ran;Ha, Boram;Kim, Yi-Jun;Jung, Wonguen;Lee, Rena;Kim, Seung Cheol;Moon, Hye Sung;Ju, Woong;Kim, Yun Hwan;Lee, Jihae
    • Radiation Oncology Journal
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    • 제34권4호
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    • pp.265-272
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    • 2016
  • Purpose: The purpose of this study is to evaluate the treatment outcomes of adjuvant radiotherapy using vaginal brachytherapy (VB) with a lower dose per fraction and/or external beam radiotherapy (EBRT) following surgery for patients with stage I endometrial carcinoma. Materials and Methods: The subjects were 43 patients with the International Federation of Gynecology and Obstetrics (FIGO) stage I endometrial cancer who underwent adjuvant radiotherapy following surgery between March 2000 and April 2014. Of these, 25 received postoperative VB alone, while 18 received postoperative EBRT to the whole pelvis; 3 of these were treated with EBRT plus VB. The median EBRT dose was 50.0 Gy (45.0-50.4 Gy) and the VB dose was 24 Gy in 6 fractions. Tumor dose was prescribed at a depth of 5 mm from the cylinder surface and delivered twice per week. Results: The median follow-up period for all patients was 57 months (range, 9 to 188 months). Five-year disease-free survival (DFS) and overall survival (OS) for all patients were 92.5% and 95.3%, respectively. Adjuvant radiotherapy was performed according to risk factors and stage IB, grade 3 and lymphovascular invasion were observed more frequently in the EBRT group. Five-year DFS for EBRT and VB alone were 88.1% and 96.0%, respectively (p = 0.42), and 5-year OS for EBRT and VB alone were 94.4% and 96%, respectively (p = 0.38). There was no locoregional recurrence in any patient. Two patients who received EBRT and 1 patient who received VB alone developed distant metastatic disease. Two patients who received EBRT had severe complications, one each of grade 3 gastrointestinal complication and pelvic bone insufficiency fracture. Conclusion: Adjuvant radiotherapy achieved high DFS and OS with acceptable toxicity in stage I endometrial cancer. VB (with a lower dose per fraction) may be a viable option for selected patients with early-stage endometrial cancer following surgery.