• 동의생리병리학회지
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• 제23권3호
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• pp.673-677
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• 2009

In order to verify the anti-inflammatory effects of Gelidium amansii, RAW264.7 macrophages were incubated with the extract of 70% ethanol solution (Ex), and activated with the endotoxin lipopolysaccharide (LPS). Ex inhibited the expression of the pro-inflammatory enzymes, including inducible nitric oxide (NO) synthase (iNOS) and cyclooxygenase-2 (COX-2), and the production of iNOS-mediated NO and COX-2-mediated prostglandin $E_2$ ($PGE_2$) production in a dose-dependent manner. Ex also reduced the release of the pro-inflammatory cytokines, including tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin-1${\beta}$ (IL-1${\beta}$) and IL-6 in LPS-activated macrophages, The observed anti-inflammatory effects of Ex was associated with inactivation of the nuclear factor ${\kappa}B$ (NF-${\kappa}B$) that mediates the induction of iNOS, COX-2, TNF-${\alpha}$, IL-1${\beta}$, and IL-6. Further studies showed that Ex inactivated NF-${\kappa}B$ through inhibition of phosphorylation of the inhibitory ${\kappa}B$ ($l{\kappa}B$), Taken together, these results suggest that Gelidium amansii exerts anti-inflammatory effects by inhibiting the expression of pro-inflammatory enzymes and the secretion of pro-inflammatory cytokines via inactivation of NF-${\kappa}B$ and/or $l{\kappa}B$.

• 한국식품저장유통학회지
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• 제19권2호
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• pp.287-293
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• 2012

본 연구에서는 HMGB1 의해 증가되는 각종 염증관련물질에 대해 라이코펜이 가지는 저해 역할을 규명하고 하였다. 라이코펜은 HMGB1에 의해 증가되는 MCP-1, IL-8, sPLA2-IIA, PGE2의 발현을 NF-${\kappa}B$ 그리고 TNF-${\alpha}$의 활성를 저해함으로써 감소시켰다. 특히, 1 mM에서 그 효능이 통계적으로 유효하였다. 결론적으로 HMGB1에 의해서 발생하는 각종 혈관염증질환에서 라이코펜은 증가하는 각종 염증관련물질을 저해하였고, 결국 라이코펜이 패혈증을 포함하는 염증질환을 효과적으로 치료할 수 있는 방법에 있어 많은 방향성을 제시할 것으로 기대한다.

• Bulletin of the Korean Chemical Society
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• 제20권9호
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• pp.1078-1084
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• 1999

A synthetic cecropin A(1-13)-melittin(1-13) [CA-ME] hybrid peptide was known to be an antimicrobial peptide having strong antibacterial, antifungal and antitumor activity with minimal cytotoxic effect against human erythrocyte. Analogues were synthesized to investigate the influences of the flexible hinge region of CA-ME on the antibiotic activity. Antibiotic activity of the peptides was measured by the growth inhibition against bac-terial, fungal and tumor cells and vesicle-aggregating or disrupting activity. The deletion of Gln-Gly-Ile (P1) or Gly-Gln-Gly-Ile-Gly (P3) from CA-ME brought about a significant decrease on the antibiotic activities. In contrast, Gly-Ile-Gly deletion (P2) from CA-ME or Pro insertion (P5) instead of Gly-Gln-Gly-Ile-Gly of CA-ME retained antibiotic activity. This result indicated that the flexible hinge or β-bend structure provided by Gly-Gln-Gly-Ile-Gly, Gln-Gly, or Pro in the central region of the peptides is requisite for its effective antibiotic activity and may facilitate easily the hydrophobic C-terminal region of the peptide to penetrate the lipid bilayers of the target cell membrane. In contrast, P4 and P6 with Gly-Gln-Gly-Pro-Gly or Gly-Gln-Pro in the central region of the peptide caused a drastic reduction on the antibiotic activities. This result suggested that the con-secutive β-bend structure provided by Gly-Gln-Gly-Pro-Gly or Gly-Gln-Pro in the central hinge region of the peptide seems to interrupt the ion channel/pore formation on the target cell membranes.

• 한국의학물리학회지:의학물리
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• 제29권4호
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• pp.106-114
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• 2018

This study aimed to compare the performance of previous optimization algorithms against new a photon optimizer (PO) algorithm for intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) plans for prostate cancer. Eighteen patients with prostate cancer were retrospectively selected and planned to receive 78 Gy in 39 fractions of the planning target volume (PTV). All plans for each patient optimized with the dose volume optimizer (DVO) and progressive resolution optimizer (PRO) algorithms for IMRT and VMAT were compared against plans optimized with the PO within Eclipse version 13.7. No interactive action was performed during optimization. Dosimetric and radiobiological indices for the PTV and organs at risk were analyzed. The monitor units (MU) per plan were recorded. Based on the plan quality for the target coverage, prostate IMRT and VMAT plans using the PO showed an improvement over DVO and PRO. In addition, the PO generally showed improvement in the tumor control probability for the PTV and normal tissue control probability for the rectum. From a technical perspective, the PO generated IMRT treatment plans with fewer MUs than DVO, whereas it produced slightly more MUs in the VMAT plan, compared with PRO. The PO showed over potentiality of DVO and PRO whenever available, although it led to more MUs in VMAT than PRO. Therefore, the PO has become the preferred choice for planning prostate IMRT and VMAT at our institution.

• Asian Pacific Journal of Cancer Prevention
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• 제17권4호
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• pp.1649-1654
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• 2016

Tea derived from the leaves and buds of Camellia sinensis (Theaceae) is consumed worldwide. Green tea contains various components with specific health-promoting effects, and is believed to exert protective effects against diseases including cancer, diabetes and hepatitis, as well as obesity. Of the various tea components, the polyphenol catechins have been the subject of extensive investigation and among the catechins, (-)-epigallocatechin gallate has the strongest bioactivity in most cases. Our research group has postulated that hepatocyte nuclear factor-$4{\alpha}$, sterol regulatory element-binding proteins, and tumor necrosis factor-${\alpha}$ are targets of green tea constituents including (-)-epigallocatechin gallate for their anti-diabetes, anti-obesity, and anti-hepatitis effects, respectively. Published papers were reviewed to determine whether the observed changes in these factors can be correlated with anti-cancer effects of green tea. Two major action mechanisms of (-)-epigallocatechin gallate have been proposed; one associated with its anti-oxidative properties and the other with its pro-oxidative activity. When reactive oxygen species are assumed to be involved, our findings that (-)-epigallocatechin gallate downregulated hepatocyte nuclear factor-$4{\alpha}$, sterol regulatory element-binding proteins, and tumor necrosis factor-${\alpha}$ may explain the anti-cancer effect of green tea as well. However, further studies are required to elucidate which determinant directs (-)-epigallocatechin gallate action as an anti-oxidant or a pro-oxidant for favorable activity.

• Molecules and Cells
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• 제21권2호
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• pp.167-173
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• 2006

The literature provides strong precedent for both pro-tumorigenic and tumor suppressor roles for the c-Jun N-terminal kinases (JNKs) in the setting of oncogenesis. Clearly, JNKs are activated by numerous oncogenes and growth factors and the literature documents a role for these MAP kinases in cell proliferation and transformation. By contrast, JNKs mediate signals from diverse stimuli that result in cell death or differentiation and a role for JNKs as tumor suppressors has emerged. This enigmatic nature of the JNKs in the setting of oncogenesis is considered herein. Further illumination of the complex and context-dependent functions of the JNKs in cancer cells is of obvious importance for the rational use of small molecule JNK inhibitors as therapeutics.

• Investigative Magnetic Resonance Imaging
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• 제18권2호
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• pp.120-132
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• 2014

목적: 원발성 뇌종양환자에서 방사선 치료 후 추적 자기공명영상에서 새로 생긴 조영증강 뇌병변에 대해 종양재발과 지연성 방사선치료연관변화의 감별에 있어서 확산강조영상 (DWI), 역동적조영관류영상 (DSC PWI), 자화율강조영상 (SWI)의 진단적 가치를 서로 비교하고자 한다. 대상과 방법: 원발성 뇌종양으로 이전에 방사선치료를 받았던 환자 중, 방사선치료 종료 최소 1년 이후에 추적 자기공명영상에서 새롭게 조영증강 되는 병변을 가진 24명의 환자를 대상으로 연구하였다. 새롭게 조영증강 되는 병변은 14명의 종양재발과 10명의 방사선치료연관변화로 확인되었다. 종양재발과 방사선치료연관변화 두 환자 군의 여러변수들은 비대응표본 t 검정을 실시하여 비교 분석하였다. 다중변수 로지스틱 회귀 분석을 이용하여 DWI, DSC PWI, SWI 각 영상의 정량 분석을 통해 얻은 apparent diffusion coefficient (ADC), normalized cerebral blood volume (nCBV), proportion of dark signal intensity (proSWI) 값 중 두 군을 감별해 내는 최상의 예측 변수 (best predictor)를 정하였다. 이후 수신자 조작 특성 (Receiver operating characteristics, ROC) 분석을 통하여 best predictor의 정확도, 민감도, 특이도를 평가하였다. 결과: 방사선치료연관변화 군과 비교하여 종양재발 군에서 평균 nCBV 값이 유의하게 높았고 (P=.004), 평균 proSWI 값은 유의하게 낮았다 (P<.001). 반면, 평균 ADC 값은 두 군간에 유의한 차이를 보이지 않았다. 다중변수 로지스틱 회귀 분석 결과 proSWI 값만이 통계적으로 유의한, 감별 가능한 독립변수였으며, 민감도, 특이도, 정확도는 각각 78.6% (11 of 14), 100% (10 of 10), 87.5% (21 of 24) 였다. 결론: 뇌종양 환자에서 방사선치료 종료 최소 1년 이후에 새로 보이는 조영증강 병변의 감별에 있어 proSWI 값이 가장 중요한 변수인 것으로 나타났다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권22호
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• pp.9593-9597
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• 2014

Ursolic acid, extracted from the traditional Chinese medicine bearberry, can induce apoptosis of gastric cancer cells. However, its pro-apoptotic mechanism still needs further investigation. More and more evidence demonstrates that mitochondrial translocation of cofilin-1 appears necessary for the regulation of apoptosis. Here, we report that ursolic acid (UA) potently induces the apoptosis of gastric cancer SGC-7901 cells. Further mechanistic studies revealed that the ROCK1/PTEN signaling pathway plays a critical role in UA-mediated mitochondrial translocation of cofilin-1 and apoptosis. These findings imply that induction of apoptosis by ursolic acid stems primarily from the activation of ROCK1 and PTEN, resulting in the translocation of cofilin-1 from cytoplasm to mitochondria, release of cytochrome c, activation of caspase-3 and caspase-9, and finally inducing apoptosis of gastric cancer SGC-7901 cells.

• The Korean Journal of Physiology and Pharmacology
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• 제23권6호
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• pp.501-508
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• 2019

Rosmarinic acid (RA) is a natural polyphenolic compound that exists in many medicinal species of Boraginaceae and Lamiaceae. The previous studies have revealed that RA had therapeutic effects on hepatocellular carcinoma (HCC) in the H22-xenograft models by inhibiting the inflammatory cytokines and $NF-{\kappa}B$ p65 pathway in the tumor microenvironment. However, its molecular mechanisms of immunoregulation and pro-apoptotic effect in HCC have not been fully explored. In the present study, RA at 75, 150, and 300 mg/kg was given to H22 tumor-bearing mice via gavage once a day for 10 days. The results showed that RA can effectively inhibit the tumor growth through regulating the ratio of $CD4^+/CD8^+$ and the secretion of interleukin (IL)-2 and interferon-${\gamma}$, inhibiting the expressions of IL-6, IL-10 and signal transducer and activator of transcription 3, thereby up-regulating Bax and Caspase-3 and down-regulating Bcl-2. The underlying mechanisms involved regulation of immune response and induction of HCC cell apoptosis. These results may provide a more comprehensive perspective to clarify the anti-tumor mechanism of RA in HCC.

• IMMUNE NETWORK
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• 제16권1호
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• pp.75-84
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• 2016

Cancer is one of the leading causes of morbidity and mortality worldwide; therefore there is a need to discover new therapeutic modules with improved efficacy and safety. Immune-(cell) therapy is a promising therapeutic strategy for the treatment of intractable cancers. The effectiveness of certain chemotherapeutics in inducing immunogenic tumor cell death thus promoting cancer eradication has been reported. Ginsenoside Rg3 is a ginseng saponin that has antitumor and immunomodulatory activity. In this study, we treated tumor cells with Rg3 to verify the significance of inducing immunogenic tumor cell death in antitumor therapy, especially in DC-based immunotherapy. Rg3 killed the both immunogenic (B16F10 melanoma cells) and non-immunogenic (LLC: Lewis Lung Carcinoma cells) tumor cells by inducing apoptosis. Surface expression of immunogenic death markers including calreticulin and heat shock proteins and the transcription of relevant genes were increased in the Rg3-dying tumor. Increased calreticulin expression was directly related to the uptake of dying tumor cells by dendritic cells (DCs): the proportion of CRT⁺CD11c⁺cells was increased in the Rg3-treated group. Interestingly, tumor cells dying by immunogenic cell death secreted IFN-γ, an effector molecule for antitumor activity in T cells. Along with the Rg3-induced suppression of pro-angiogenic (TNF-α) and immunosuppressive cytokine (TGF-β) secretion, IFN-γ production from the Rg3-treated tumor cells may also indicate Rg3 as an effective anticancer immunotherapeutic strategy. The data clearly suggests that Rg3-induced immunogenic tumor cell death due its cytotoxic effect and its ability to induce DC function. This indicates that Rg3 may be an effective immunotherapeutic strategy.