• Asian Pacific Journal of Cancer Prevention
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• 제16권3호
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• pp.1001-1006
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• 2015

Background: With development and application of new and effective anti-cancer drugs, the median survival post-progression (SPP) is often prolonged, and the role of the median SPP on surrogacy performance should be considered. To evaluate the impact of the median SPP on the correlation between progression-free survival (PFS) and overall survival (OS), we performed simulations for treatment of four types of cancer, advanced gastric cancer (AGC), metastatic colorectal cancer (MCC), glioblastoma (GBM), and advanced non-small-cell lung cancer (ANSCLC). Materials and Methods: The effects of the median SPP on the statistical properties of OS and the correlation between PFS and OS were assessed. Further, comparisons were made between the surrogacy performance based on real data from meta-analyses and simulation results with similar scenarios. Results: The probability of a significant gain in OS and HR for OS was decreased by an increase of the SPP/OS ratio or by a decrease of observed treatment benefit for PFS. Similarly, for each of the four types of cancer, the correlation between PFS and OS was reduced as the median SPP increased from 2 to 12 months. Except for ANSCLC, for which the median SPP was equal to the true value, the simulated correlation between PFS and OS was consistent with the values derived from meta-analyses for the other three kinds of cancer. Further, for these three types of cancer, when the median SPP was controlled at a designated level (i.e., < 4 months for AGC, < 12 months for MCC, and <6 months for GBM), the correlation between PFS and OS was strong; and the power of OS reached 34.9% at the minimum. Conclusions: PFS is an acceptable surrogate endpoint for OS under the condition of controlling SPPs for AGC, MCC, and GBM at their limit levels; a similar conclusion cannot be made for ANSCLC.

• The Korean Journal of Physiology and Pharmacology
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• 제15권4호
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• pp.241-244
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• 2011

A lectin from the hemolymph of purse crab, Philyra pisum, was found to have anti-proliferative activity on human lung cancer cells by our laboratory. In this study, P. pisum lectin (PPL) was molecularly characterized including molecular mass, amino acid sequences, amino acid composition, and the effects of metal ions, temperature, and pH on the activity. We found that PPL showed mitogenic activity on human lymphocytes and BALB/c mouse splenocytes. The mitogenic activity (maximum stimulation index, $SI=9.57{\pm}0.59$) of PPL on human lymphocytes was higher than that of a standard well-known plant mitogen, concanavalin A (maximum $SI=8.80{\pm}0.59$). The mitogenic activity mediated by PPL is required for optimum dosing, and higher or lower concentrations caused decreases in mitogenic response. PPL also induced mitogenic activity on mouse splenocytes, however, the maximum SI ($1.77{\pm}0.09$) on mouse splenocytes of PPL was lower than that ($2.14{\pm}0.15$) of concanavalin A. In conclusion, PPL is a metal ion-dependent monomer lectin with mitogenic activity, and could be used as a lymphocyte or splenocyte stimulator.

• 한국식품영양과학회지
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• 제44권2호
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• pp.208-215
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• 2015

본 연구에서는 들깨 에탄올 추출물의 항산화 성분 함량 및 활성을 측정하고 들깨 추출물이 암세포의 주요 특징인 성장, colony 형성, 이동, 부착성 등에 미치는 영향을 in vitro 수준에서 분석하고자 하였다. 들깨의 총 폴리페놀 함량과 총 플라보노이드 함량은 각각 222.6 mg gallic acid equivalent/100 g과 285.7 mg quercetin equivalent/100 g으로 측정되었다. 들깨 추출물($87.5{\sim}350{\mu}g/mL$)의 DPPH radical 소거 활성은 24~45%, 철 환원력은 28~62%였다. 한편 $87.5{\sim}350{\mu}g/mL$ 농도의 들깨 추출물은 HCT116 대장암 세포와 H1299 폐암 세포의 성장을 18~94% 억제하는 농도 의존적 활성이 있었다. 또한 $175{\mu}g/mL$ 농도의 들깨 추출물은 HCT116과 H1299 세포에서 모두 colony 형성을 완전히 억제하는 활성이 있었다. 또한 들깨 추출물은 $87.5{\sim}350{\mu}g/mL$ 농도에서 H1299 세포의 이동을 30~37% 억제하였고, 가장 높은 농도인 $350{\mu}g/mL$ 농도에서는 HCT116과 H1299 세포의 부착을 14~16% 억제하였다. 이상의 결과를 통하여 들깨 추출물은 항산화 활성 및 암세포의 주요 특징을 억제하는 활성을 가지는 것으로 생각되며, 향후 이러한 연구 결과가 in vivo 수준에서 재현되는지 여부와 본 활성과 관련된 세부작용기전 또한 규명되어야 할 것으로 생각된다.

• Tuberculosis and Respiratory Diseases
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• 제62권1호
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• pp.33-42
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• 2007

연구배경: 다양한 고형암에서 HO-1의 높은 발현이 알려져 있고, 그것의 항산화와 항세포고사의 역할로 인해 빠른 암종의 성장에 중요한 역할이 있음이 보고되고 있다. 대표적인 활성산소종 생성 항암제인 Cisplatin은 현재까지 폐암치료에 가장 광범위하게 사용되고 있으나, 여러 내성발생이 임상치료의 주요문제로 대두되고 있다. 저자들은 A549 폐암세포주에서 HO-1의 발현이 증가되었고 HO-1 활성억제제나 siRNA 방법을 통해 생존율의 의미 있는 감소와 세포고사가 유도됨을 보고한 바 있다. 이 연구의 목적은 A549 폐암세포주에 cisplatin 처리시 HO-1의 발현의 증가유무와 기전을 규명하고 실제 HO-1의 억제가 cisplatin에 의한 항암제 감수성을 증가시키는지를 알아보는데 있다. 방 법: 비소세포폐암세포주인 A549, NCI-H23, NCIH157, NCI-H460을 이용하였다. 세포독성은 MTT 방법으로 구하였고, HO-1, Nrf2, MAPK의 발현은 Western blotting으로 확인하였다. 또한 MAPK억제제들을 전처치한 후 cisplatin에 의해 유도된 Nrf2와 HO-1의 발현에 미치는 영향을 역시 Western blotting으로 관찰하였다. A549세포에 활성억제제인 ZnPP나 HO-1 small interfering RNA (siRNA)을 주입하여 cisplatin과의 병합요법시 생존율의 배가효과 유무를 MTT 방법으로 확인하였고, 이러한 효과가 ROS 형성과 HO-1의 발현변화와 관련되는지를 알아보기 위해 $carboxy-H_2DCFDA$ 방법과 Western blotting을 통해 각각 확인하였다. 결 과: Cisplatin 처리시 다른 세포주에 비해 A549 세포가 의의 있게 내성을 보였다. $10{\mu}M$의 농도에서 시간 의존적으로 HO-1, Nrf2, MAPK의 발현이 증가하였고, MAPK 억제제들을 전 처치하였을 때 cisplatin에 의해 유도된 HO-1과 Nrf2의 발현이 억제됨을 확인하였다. HO-1의 활성억제제인 ZnPP와 HO-1 siRNA를 통해 HO-1 mRNA를 직접 억제하는 방법으로 cisplatin과 병합치료시 단독치료에 비해 의의 있는 생존율의 감소를 보였다. 이러한 효과는 활성산소종의 생성 증가와 HO-1의 발현억제에 의한 결과임을 확인하였다. 결 론: Cisplatin 처리시 HO-1의 발현은 MAPKNrf2-HO-1의 경로를 통해 증가하였고, 부분적으로 치료에 대한 내성과 관련이 있었으며, ZnPP 등의 활성억제제나 siRNA를 통한 knock-down 방법으로 HO-1 을 표적으로 억제하는 치료방법을 통해 cisplatin의 항암제 감수성을 증가시켰다.

• Nutrition Research and Practice
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• 제11권2호
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• pp.83-89
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• 2017

BACKGROUND/OBJECTIVES: Epithelial-mesenchymal transition (EMT) is involved in not only cancer development and metastasis but also non-cancerous conditions. Hypoxia is one of the proposed critical factors contributing to formation of chronic rhinosinusitis or nasal polyposis. Wheatgrass (Triticum aestivum) has antioxidant, anti-aging, and anti-inflammatory effects. In this study, we analyzed whether wheatgrass has an inhibitory effect on the EMT process in airway epithelial cells. MATERIALS/METHODS: A549 human lung adenocarcinoma cells were incubated in hypoxic conditions ($CO_2$ 5%/$O_2$ 1%) for 24 h in the presence of different concentrations of wheatgrass extract (50, 75, 100, and $150{\mu}g/mL$) and changes in expression of epithelial or mesenchymal markers were evaluated by immunoblotting and immunofluorescence. Accordingly, associated EMT-related transcriptional factors, Snail and Smad, were also evaluated. RESULTS: Hypoxia increased expression of N-cadherin and reduced expression of E-cadherin. Mechanistically, E-cadherin levels were recovered during hypoxia by silencing hypoxia inducible factor (HIF)-$1{\alpha}$ or administering wheatgrass extract. Wheatgrass inhibited the hypoxia-mediated EMT by reducing the expression of phosphorylated Smad3 (pSmad3) and Snail. It suppressed the hypoxia-mediated EMT processes of airway epithelial cells via HIF-$1{\alpha}$ and the pSmad3 signaling pathway. CONCLUSION: These results suggest that wheatgrass has potential as a therapeutic or supplementary agent for HIF-1-related diseases.

• 한국식품과학회지
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• 제35권1호
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• pp.132-137
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• 2003

국내에서 생산된 거봉 및 캠벨 포도의 씨, 줄기 및 껍질 추출물에 대하여 항산화 작용, 염증 관련 인자 생성에 미치는 활성 및 암세포 성장에 대한 영향 등을 resveratrol과 비교하여 평가하였다. 그 결과 포도 추출물 중 거봉줄기, 캠벨줄기, 캠벨씨 및 거봉씨 추출물들이 항산화 능력을 나타내었고 그 중 거봉씨 추출물은 vitamin C와 효력이 유사하게 나타나 항산화 효능이 우수함을 알 수 있었다. 또한 마우스 대식세포주인 RAW 264.7 cell을 이용하여 포도 추출물들의 LPS처리에 의한 $PGE_2$ 및 NO 생성을 저해 여부를 확인한 결과, 거봉줄기, 거봉씨, 및 캠벨씨 추출물이 $50\;{\mu}g/mL$에서 $PGE_2$ 및 NO 생성을 50% 가량 저해하는 효능을 나타내었다. 또한 사람 폐암 및 대장암 세포주를 이용하여 포도 추출물들이 암세포 성장 저해 효과를 나타내는지를 확인하였는데 거봉줄기 및 씨 추출물 $50\;{\mu}g/mL$에서 30% 정도의 암세포 성장 저해 작용을 나타내었다.

• Journal of Microbiology and Biotechnology
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• 제31권2호
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• pp.197-206
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• 2021

microRNA-361-3p (miR-361-3p) is involved in the carcinogenesis of oral cancer and pancreatic catheter adenocarcinoma, and has anti-carcinogenic effects on non-small cell lung cancer (NSCLC). However, its effect on multiple myeloma (MM) is less reported. Here, we found that upregulating the expression of miR-361-3p inhibited MM cell viability and promoted MM apoptosis. We measured expressions of tumor necrosis factor receptor-associated factor 6 (TRAF6) and miR-361-3p in MM cells and detected the viability, colony formation rate, and apoptosis of MM cells. In addition, we measured expressions of apoptosis-related genes Bcl-2, Bax, and Cleaved caspase-3 (C caspase-3). The binding site between miR-361-3p and TRAF6 was predicted by TargetScan. Our results showed that miR-361-3p was low expressed in the plasma of MM patients and cell lines, while its overexpression inhibited viability and colony formation of MM cells and increased the cell apoptosis. Furthermore, TRAF6, which was predicted to be a target gene of miR-361-3p, was high-expressed in the plasma of patients and cell lines with MM. Rescue experiments demonstrated that the effect of TRAF6 on MM cells was opposite to that of miR-361-3p. Upregulation of miR-361-3p induced apoptosis and inhibited the proliferation of MM cells through targeting TRAF6, suggesting that miR-361-3p might be a potential target for MM therapy.

• Toxicological Research
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• 제26권3호
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• pp.217-222
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• 2010

Many studies have reported that bleomycin, anti-cancer drug, induces pulmonary fibrosis as a side effect. However, few investigations have focused on the dose-response effects of bleomycin on pulmonary fibrosis. Therefore, in the present study, we investigated the effects of different doses of bleomycin in male mice. ICR mice were given 3 consecutive doses of bleomycin: 1, 2, or 4 mg/kg in bleomycin-treated (BT) groups and saline only in vehicle control (VC) groups. The animals were sacrificed at 7 and 24 days postinstillation. The severity of pulmonary fibrosis was evaluated according to inflammatory cell count and lactate dehydrogenase (LDH) activity in the broncho alveolar lavage fluid (BALF), and lung tissues were histologically evaluated after hematoxylin and eosin (H&E), and Masson's trichrome staining. BT groups exhibited changed cellular profiles in BAL fluid compared to the VC group, which had an increased number of total cells, neutrophils, and lymphocytes and a modest increase in the number of macrophages at 7 days post-bleomycin instillation. Moreover, BT groups showed a dose-dependent increase in LDH levels and inflammatory cell counts. However, at 24 days after treatment, collagen deposition, interstitial thickening, and granulomatous lesions were observed in the alveolar spaces in addition to a decrease in inflammatory cells. These results indicate that pulmonary fibrosis induced by 4 mg/kg bleomycin was more severe than that induced by 1 or 2 mg/kg. These data will be utilized in experimental animal models and as basic data to evaluate therapeutic candidates through non-invasive monitoring using the pulmonary fibrosis mouse model established in this study.

• 대한한방내과학회지
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• 제33권2호
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• pp.126-144
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• 2012

Background : Peripheral nerves more rapidly recover than central nerves. However, it has been known that the degree of reaction of axons of peripheral nerves is affected by distinctive characteristics of axons and environmental factors near the axons. Taxol is a widely used medicine as for ovarian, breast, lung and gastric cancer. However it causes patients difficulties under treatment due to its toxic and side effects, which include persistent pain. Objectives : This study reviewed how SJT extract in vitro and in vivo affects nerve tissues of a sciatic nerve damaged by Taxol. It also studied how SJT extract in vivo affects axons of the sciatic nerve after the sciatic nerve was damaged by pressing. Methods : After vehicle, Taxol, and Taxol plus SJT were treated respectively for tissue of the sciatic nerve in vitro and then tissues were observed using Neurofilament 200, Hoechst, ${\beta}$-tubulin, $S100{\beta}$, caspase-3 and anti-cdc2. SJT was also oral medicated by injecting Taxol into the sciatic nerve of in vivo rats. Tissues of the sciatic nerve and axons of DRG sensory nerves were then observed using Neurofilament 200, Hoechst, ${\beta}$-tubulin, $S100{\beta}$, caspase-3 and p-Erk1/2. After inflicting pressing damage to the sciatic nerve of in vivo rats, tissues of the sciatic nerve and DRG sensory nerve were observed using Neurofilament 200, Hoechst, $S100{\beta}$, caspase-3, anti-cdc2, phospho-vimentin, ${\beta}1$-integrin, Dil reverse tracking and p-Erk1/2. Results : The group of in vitro Taxol plus SJT treatment had meaningful effects after sciatic nerve tissue was damaged by Taxol. The group of in vivo SJT treatment had effects of regenerating Schwann cells and axons which were damaged by Taxol treatment. The group of in vivo SJT had effects of regenerating axons in damaged areas after the sciatic nerve was damaged by pressing, and also had variations of distribution in Schwann cells at DRG sensory nerves and axons. Conclusions : This study confirmed that SJT treatment is effective for growth of axons in the sciatic nerve tissues and improvement of Schwann cells after axons of the sciatic nerve tissues was damaged. After tissues of sciatic nerve was damaged by pressing in vivo, SJT treatment had effects on promoting regeneration of axon in the damaged area and reactional capabilities in axons of DRG sensory nerves.

• Toxicological Research
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• 제24권2호
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• pp.151-159
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• 2008

Rhus verniciflua Stokes(RVS), one of traditional medicinal plants in Asia, was found to have pharmacological activities such as antioxidative and antiapoptotic effects, raising the possibility for the development of a novel class of anti-cancer drugs. Thus, potential genotoxic effects of RVS in three short-term mutagenicity assays were investigated, which included the Ames assay, in vitro Chromosomal aberration test, and the in vivo Micronucleus assay. In Ames test, the addition of RVS water extracts at doses from 313 up to 5000 mg/plate induced an increase more than 2-fold over vehicle control in the number of revertant colonies in TA98 and TA1537 strains for detecting the frame-shift mutagens. The similar increase in reversion frequency was observed after the addition of RVS ethanol extracts. To assess clastogenic effect, in vitro chromosomal aberration test and in vivo micronucleus assay were performed using Chinese hamster lung cells and male ICR mice, respectively. Both water and ethanol extracts from RVS induced significant increases in the number of metaphases with structural aberrations mostly at concentrations showing the cell survival less than 60% as assessed by in vitro CA test. Also, there was a weak but statistically significant increase in number of micronucleated polychromatic erythrocytes(MNPCEs) in mice treated with water extract at 2000 mg/kg while ethanol extracts of RVS at doses of up to 2000 mg/kg did not induce any statistically significant changes in the incidence of MNPCEs. Therefore, our results lead to conclusion that RVS acts as a genotoxic material based on the available in vitro and in vivo results.