• 약학회지
• /
• 제48권6호
• /
• pp.335-344
• /
• 2004

Interleukin-2 (IL-2), a glycoprotein mainly secreted by CD4+ T helper Iymphocytes, has been developed to use recombinant cytokine to augment the immune response against cancer since IL-2 not only stimulates T Iymphocytes but also enhances natural killer (NK) cell activity. In order to evaluate the immunological safety of recombinant mouse IL-2 (rmIL-2) in cancer therapy, renal cell carcinoma was established in the flank by s.c. injection of renca cell line. Tumor-bearing BALB/c mice were treated with I.p. injections with $2{\times}10^5$ Lu rmIL-2. Even though the tumor size was diminished, there were not significant recovery of body and relative lymphoid organ weights including thymic atrophy in rmIL-2 immunotherapy. Distribution ratios of T cell subsets in thymus were analysed using flow cytometry. Without regard to dosage of rmIL-2, the ratio of CD3+CD4-CD8- T cells was increased in accordance with survival of solid tumor but that of CD4+CD8+ T cells was decreased dramatically. Emergence of autoantibodies (ANA, anti-dsDNA, and anti-histone) in blood was measured after rmIL-2 treatment. The results showed that the levels of ANA and anti-dsDNA did not significantly changed, but the level of anti-histone was increased significantly owing to rmIL-2 therapy. These results indicate rmIL-2 immunotherapy is to induce the autoimmune potential, and the anti-histone measurement as a biomarker of autoimmunity is useful in cancer immunotherapy.

• 대한방사선기술학회지:방사선기술과학
• /
• 제29권4호
• /
• pp.225-228
• /
• 2006

목 적: 후족부의 병리학적 상태의 치료와 평가를 위해서는 관상면에서 종골과 경골이 연관된 배열상태의 정확한 평가가 필수적이다. 이전의 방사선학적 검사인 발과 발목의 전후방향, 측방향, 사방향 촬영과 종골 축방향 촬영 등의 X-선 촬영상은 관상면에서 종골과 경골이 연관된 배열상태를 증명하지 못했다. 이에 본 연구에서는 후족부 관상면 배열영상(hindfoot coronal alignment view)을 새롭게 소개하고자 한다. 검사방법 : 1) 양쪽 발을 지탱할 수 있는 방사선투과성의 스탠드형 보조기구를 제작한다. 2) 양측 발은 weight-bearing position이 되게 한다. 3) 각각의 발의 위치는 발의 종축이 보조기구 판과 수직이 되도록 자세를 유지한다. 4) silhouette tracing: 발뒷꿈치 outline과 둘째 발가락이 일직선상으로 지나도록 위치시킨다. 5) 중심 X-선: 발바닥 쪽을 향해 약 $15{\sim}20^{\circ}의 각도로 종골의 뒷쪽을 향해 입사한다. 결 과 : 1) 경골 축과 종골의 내측, 외측 결절의 영상이 함께 표출된다. 2) 종골이 회전되지 않아야 한다. 3) 거퇴관절강(talotibial joint space)이 함께 나타나야 한다. 결 론: CT나 MRI 영상에서도 관상면에서 후족부의 배열상태를 증명할 수 있지만, 환자의 체중이 주어지지 않기 때문에 발의 임상적인 증상을 보여주기에는 충분하지 못했다. 하지만 후족부 관상면 배열영상은 후족부의 inversion, eversion의 자세변화를 보여주고, 경골 원위부와 종골의 varus, valgus deformity의 치료를 위한 평가 자료로 좋은 검사방법이며, 비교적 자연스럽고 편안한 자세로 환자에게 큰 도움을 줄 것으로 사료된다.

• 한국가스학회지
• /
• 제26권6호
• /
• pp.24-29
• /
• 2022

이 논문은 LPG 자동차의 캠축베어링 시일의 오일누설, 컴퓨터커넥터 핀 손상에 의한 접촉불량, 베이퍼라이저 배부불량으로 인한 고장사례에 대하여 현상을 분석, 연구한 것이다. 첫 번째 사례는 실린더 헤드를 분해하여 확인한 결과 타이밍 시스템에서 가까운 엔진의 흡기캠축의 베어링과 시일의 조립부 손상으로 인해 이 부위로 엔진오일이 누설되는 것을 확인하였다. 두 번째 사례는 엔진컴퓨터로 공급되는 자동차의 시동을 제어하는 전원선의 커넥터 핀이 손상되어, 전원이 공급되지 않아 시동이 꺼진 것을 확인하였다. 세 번째 사례는 베이퍼라이저 내부에 이물질의 퇴적으로 인해 가스의 흐름이 원활하지 못하여 엔진의 부조화현상이 발생되었다. 결국, 베이퍼라이저에서 믹서로 적은 양의 가스를 공급하게 되고, 믹서의 스로틀 열림량을 제어하는 컴퓨터는 그 열림량만큼 공기를 공급하게 됨으로써 연소실에서 혼합기는 희박한 상태가 되어 엔진의 적정출력을 내지 못하는 것을 확인하였다. 따라서, 자동차가 최적의 운전조건이 될 수 있도록 자동차관련 시스템의 관리를 철저하게 해야한다.

• 한국발생생물학회지:발생과생식
• /
• 제20권1호
• /
• pp.1-10
• /
• 2016

Molecular targeting for the altered signaling pathways has been proven to be effective for the treatment of many types of human cancer, including colorectal cancer (CRC). The dual phosphatidylinositol-3-kinase (PI3K) and mammalian target of rapamycin (mTOR) inhibitor BEZ235 has shown to exhibit potent antitumor activity against solid tumors. Autophagy is a cellular lysosomal catabolic process to maintain metabolic homeostasis, which has been known to be induced in response to many therapeutic agents in cancer cells. This process is negatively regulated by mTOR and often acts as prosurvival or prodeath mechanism following cancer therapeutics. The current study was designed to investigate the antiproliferation activity of BEZ235 and to evaluate the role of autophagy induced by BEZ235 using HCT15 CRC cells bearing ras oncogene mutation. We found that BEZ235 decreases cell viability, which was mostly dependent on $G_1$ arrest of cell cycle via suppression of cyclin A expression. BEZ235 affects PI3K/Akt/mTOR signaling pathway by increasing the phosphorylation of AKT at $Ser^{473}$ and RAS/RAF/MEK/ERK pathway by decreasing the phosphorylation of ERK at $Tyr^{204}$. BEZ235 also stimulated autophagy induction as evidenced by the increased expression of LC3-II and abundant acidic vesicular organelles (AVOs) in the cytoplasm. In addition, the combination of BEZ235 with autophagy inhibitor chloroquine, a known antagonist of autophagy, counteracted the antiproliferation effect of BEZ235. Thus, our study indicates that autophagy induced in response to BEZ235 treatment appears to act as cell death mechanism in HCT15 CRC cells.

• Mycobiology
• /
• 제40권1호
• /
• pp.47-52
• /
• 2012

$Elfvingia$ $applanata$, a medicinal mushroom belonging to Basidiomycota, has been used in the effort to cure cancers of the esophagus and stomach, and is also known to have inhibitory effects on hepatitis B virus infection. The hot water soluble fraction (as Fr. HW) was extracted from fruiting bodies of the mushroom. $In$ $vitro$ cytotoxicity tests showed that hot water extract was not cytotoxic against cancer cell lines such as Sarcoma 180, HT-29, HepG2, and TR at concentrations of 10-2,000 ${\mu}g/mL$. Intraperitoneal injection with Fr. HW resulted in a life prolongation effect of 45.2% in mice previously inoculated with Sarcoma 180. Treatment of Fr. HW resulted in a 2.53-fold increase in the numbers of murine spleen cells at a concentration of 50 ${\mu}g/mL$, compared with control. Incubation of murine spleen cells with Fr. HW at a concentration of 500 ${\mu}g/mL$ resulted in improved immune-potwntiating activity of B lymphocytes through an 8.3-folds increase in alkaline phosphatase activity, compared with control. Fr. HW generated 12.5 ${\mu}M$ of nitric oxide (NO) when cultured with RAW 264.7, a mouse macrophage cell line, at the concentration of 50 ${\mu}g/mL$, while lipopolysaccharide, a positive control, produced 15.2 ${\mu}M$ of NO. Therefore, the results suggested that antitumor activities of Fr. HW from $E.$ $applanata$ might, in part, be due to host mediated immunostimulating activity.

• 대한한방종양학회지
• /
• 제3권1호
• /
• pp.67-84
• /
• 1997

Bujeonghangamtang(扶正抗癌湯) has been used for cure of tumor as a traditional medicine without any experimental evidence to support the rational basis for its clinical use. This study was carried out to evaluate the possible therapeutic or antitumoral effects of Bujeonghangamtang extract against tumor, and to carry out some mechanisms responsible for its effect. Some kinds of tumor were induced by the typical application of 3-methylcholanthrene. (MCA) or by the implantation(s.c) of malignant tumor cells such as leukemia cells(3LL cells) or sarcoma cells(Sl80 cells). Treatment of the Bujeonghangamtang water-extract (dailly 1mg／mouse, i. p.) was continued for 7 days prior to tumor induction and after that the treatment was lasted for 20 days. Against squamous cell carcinoma induced by MCA, Bujeonghangamtang decreased not only the frequency of tumor production but also the number and the weight of tumors per tumor bearing mice (TBM). Bujeonghangamtang also significantly suppressed the development of 3LL cell and S180 cell-implanted tumors in occurrence-frequency and their size, and some developed tumors were regressed by the continuous treatment of Bujeonghangamtang extract into TBM. In vitro, treatment of Bujeonghangamtang extract had no effect on the growth of some kinds of cell line such as FsaII, A431 strain but significantly inhibited the proliferation of 3LL, S180 cells and augmented the DNA synthesis of mitogen-activated lymphocytes. Bujeonghangamtang also stimulated the migrative ability of leukocyte, the MIF and IL-2 production of T lymphocytes, but not IL 6 production of B cells. Bujeonghangamtang-administration to mice enhanced NK cells activities. These results demonstrated that Bujeonghangamtang extract exhibited a significant prophylactic benefits against tumors and its antitumor activity was manifested depending on the type of tumor cells. And these results also suggested that effect of Bujeonghangamtang might be chiefly due to nonspecific enhancement of NK cell activities and cell-mediated immune responses.

• Nutrition Research and Practice
• /
• 제8권4호
• /
• pp.377-385
• /
• 2014

BACKGROUND/OBJECTIVES: Abundant consumption of seaweeds in the diet is epidemiologically linked to the reduction in risk of developing cancer. In larger cases, however, identification of particular seaweeds that are accountable for these effects is still lacking, hindering the recognition of competent dietary-based chemo preventive approaches. The aim of this research was to establish the antiproliferative potency and angiosuppressive mode of action of Stoechospermum marginatum seaweed methanolic extract using various experimental models. MATERIALS/METHODS: Among the 15 seaweeds screened for antiproliferative activity against Ehrlich ascites tumor (EAT) cell line, Stoechospermum marginatum extract (SME) was found to be the most promising. Therefore, it was further investigated for its anti-proliferative activity in-vitro against choriocarcinoma (BeWo) and non-transformed Human embryonic kidney (HEK 293) cells, and for its anti-migratory/tube formation activity against HUVEC cells in-vitro. Subsequently, the angiosuppressive activity of S. marginatum was established by inhibition of angiogenesis in in-vivo (peritoneal angiogenesis and chorioallantoic membrane assay) and ex-vivo (rat cornea assay) models. RESULTS: Most brown seaweed extracts inhibited the proliferation of EAT cells, while green and red seaweed extracts were much less effective. According to the results, SME selectively inhibited proliferation of BeWo cells in-vitro in a dose-dependent manner, but had a lesser effect on HEK 293 cells. SME also suppressed the migration and tube formation of HUVEC cells in-vitro. In addition, SME was able to suppress VEGF-induced angiogenesis in the chorio allantoic membrane, rat cornea, and tumor induced angiogenesis in the peritoneum of EAT bearing mice. A decrease in the microvessel density count and CD31 antigen staining of treated mice peritoneum provided further evidence of its angiosuppressive activity. CONCLUSIONS: Altogether, the data underline that VEGF mediated angiogenesis is the target for the angiosuppressive action of SME and could potentially be useful in cancer prevention or treatment involving stimulated angiogenesis.

• BMB Reports
• /
• 제31권6호
• /
• pp.560-564
• /
• 1998

Echinomycin-7 is an echinomycin derivative, Smethylated sulfonium perchlorate of echinomycin. We studied the in vitro cytotoxicity and in vivo antitumor activity of echinomycin-7 against P388 leukemia cells and compared the results with echinomycin. With respect to the cytotoxic effects, echinomycin-7 had cell line-dependent $IC_{50}$ values while echinomycin had similar values to several tumor cell lines. Also, in vivo antitumor activities were observed in tumor-bearing mice treated with both agents, which showed that echinomycin-7 had a broad therapeutic dose range. We also observed the apoptosis on leukemia cells treated with echinomycin-7 which exihibited the ladder pattern of DNA on electrophoresis. In addition to apoptosis, echinomycin-7 arrested $G_1/S$ phases of the cell cycle at the same time. We then examined the signaling pathway of echinomycin-7-induced apoptosis and showed that ERK of the MAP kinase family was activated and translocated into the nucleus by echinomycin-7 stimulation. This study suggests that echinomycin-7 acts as an antitumor agent through in vitro cytotoxicity and has in vivo antitumor activity against leukemia cells, and that the echinomycin-7- induced apoptosis might involve signal transduction via MAP kinases.

• BMB Reports
• /
• 제39권2호
• /
• pp.171-177
• /
• 2006

Nonsteroidal anti-inflammatory drugs such as indomethacin (IN) can exert anti-colorectal cancer (CRC) activity through cyclooxygenase independent mechanism, but the exactly biological mechanism is not completely known. Here we use proteomic tools to investigate the molecular mechanism of this action. First, nude mice bearing tumors derived from subcutaneous injection with human CRC cell line HCT116 were randomly allocated to groups treated with or without indomethacin. Later, tumor lumps were incised and then total proteins extracted. After separated with two-dimensional electrophoresis, thirty-one differently expressed spots were found between IN-treated and non-IN-treated groups, of which 25 spots decreased and 6 spots increased in abundance in IN-treated group. Through matrix-assisted laser desorption ionization time of flight mass spectrometry and then NCBInr and SWISS-PROT databases searching, 12 protein spots were finally identified including galectin-1, annexin A1, annexin IV, trancription factor BTF3A, calreticulin. Most of the identified proteins are correlated with tumor's biological prosperities of proliferation, invasion, apoptosis and immunity, or take part in cell's signal transduction. From above we thought that indomethacin can exert its effect on colorectal cancer through regulating several proteins' expression directly or indirectly. Further study of these proteins may be helpful in founding new targets of drugs for cancer chemotherapy.

• Archives of Reconstructive Microsurgery
• /
• 제13권2호
• /
• pp.123-129
• /
• 2004

Lower extremity injuries are frequently accompanied with large soft-tissue defects. Such Injuries are difficult to manage for its poor vascularity, rigid tissue distensibility, easy infectability and a relatively long healing period. Also, osteomyelitis, and/or non-union of the fractured bones are relatively common in lower extremity injuries and its weight-bearing role should be considered. Therefore, it is important to select appropriate reconstruction method of the lower extremities, which is applicable to a variety of surgical techniques according to these considerations. The goal of flap coverage in the lower extremity should not only be satisfactory wound coverage, but also acceptable appearance and minimal donor site morbidity. In this article, we have tried to establish a reconstruction method in the lower extremity based on our experiences and clinical analysis of soft tissue reconstruction using free muscle flap transfer in 27 cases from Jan. 2000 to Dec. 2002. The results showed 96% flap survival, and flap failure noted in one of the cases due to vascular insufficiency. In conclusion, we believe that in cases of lower extremity soft-tissue defects especially with open comminuted fractures and infections, muscle free flaps should be considered as the first line of treatment.