• Asian Pacific Journal of Cancer Prevention
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• 제13권1호
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• pp.255-260
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• 2012

Patients with non-small cell lung cancer (NSCLC) who have activating epidermal growth factor receptor (EGFR) mutations derive clinical benefit from treatment with EGFR-tyrosine kinase inhibitors ((EGFR-TKIs)-namely gefitinib and erlotinib. However, these patients eventually develop resistance to EGFR-TKIs. Despite the fact that this acquired resistance may be the result of a secondary mutation in the EGFR gene, such as T790M or amplification of the MET proto-oncogene, there are other mechanisms which need to be explored. MicroRNAs (miRs) are a class of small non-coding RNAs that play pivotal roles in tumorigenesis, tumor progression and chemo-resistance. In this study, we firstly successfully established a gefitinib resistant cell line-HCC827/GR, by exposing normal HCC827 cells (an NSCLC cell line with a 746E-750A in-frame deletion of EGFR gene) to increasing concentrations of gefitinib. Then, we found that miR-214 was significantly up-regulated in HCC827/GR. We also showed that miR-214 and PTEN were inversely expressed in HCC827/GR. Knockdown of miR-214 altered the expression of PTEN and p-AKT and re-sensitized HCC827/GR to gefitinib. Taken together, miR-214 may regulate the acquired resistance to gefitinib in HCC827 via PTEN/AKT signaling pathway. Suppression of miR-214 may thus reverse the acquired resistance to EGFR-TKIs therapy.

• Asian Pacific Journal of Cancer Prevention
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• 제15권19호
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• pp.8041-8046
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• 2014

In-depth analysis of how TRAIL signals through death receptors to induce apoptosis in cancer cells using high throughput technologies has added new layers of knowledge. However, the wealth of information has also highlighted the fact that TRAIL induced apoptosis may be impaired as evidenced by experimental findings obtained from TRAIL resistant cancer cell lines. Overwhelmingly, increasing understanding of TRAIL mediated apoptosis has helped in identifying synthetic and natural compounds which can restore TRAIL induced apoptosis via functionalization of either extrinsic or intrinsic pathways. Increasingly it is being realized that biologically active phytochemicals modulate TRAIL induced apoptosis, as evidenced by cell-based studies. In this review we have attempted to provide an overview of how different phytonutrients have shown efficacy in restoring apoptosis in TRAIL resistant cancer cells. We partition this review into how the TRAIL mediated signaling landscape has broadened over the years and how TRAIL induced signaling machinery crosstalks with autophagic protein networks. Subsequently, we provide a generalized view of considerable biological activity of coumarins against a wide range of cancer cell lines and how coumarins (psoralidin and esculetin) isolated from natural sources have improved TRAIL induced apoptosis in resistant cancer cells. We summarize recent updates on piperlongumine, phenethyl isothiocyanate and luteolin induced activation of TRAIL mediated apoptosis. The data obtained from pre-clinical studies will be helpful in translation of information from benchtop to the bedside.

• Toxicological Research
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• 제33권1호
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• pp.15-23
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• 2017

Acanthopanax divaricatus (Siebold & Zucc.) Seem. var. albeofructus (ADA), a traditional medical herb, has been used to treat arthritis and muscular injury, to strengthen muscle and bone, and to get vital energy. However, information regarding its toxicity is limited. ADA was administered by oral gavage to groups of rats at doses of 0 (control), 1,000, 1,500, 2,000, 2,500, and 3,000 mg/kg five times per week for 13 weeks. Mortality, clinical signs, body weights, food consumption, hematology, serum chemistry, urinalysis, organ weights, necropsy, histopathological finding, vaginal cytology, and sperm morphology were compared between control and ADA-treated groups. Salivation was intermittently observed in both sexes receiving 2,500 and 3,000 mg/kg directly after dosing. Absolute liver weights increased in females receiving 2,000, 2,500, and 3,000 mg/kg ADA (P < 0.05, P < 0.01, and P < 0.01, respectively) and so did the relative liver weights (P < 0.001). Salivation and increased liver weight were ADA-related changes but not considered to be adverse effects. Salivation was intermittent and transient, and the liver weight increase was minor and not accompanied by other changes such as hepatic morphological or functional alterations. The no-observed-adverse-effect-level was determined to be at least 3,000 mg/kg in both sexes of rats.

• 한국식품위생안전성학회지
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• 제20권1호
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• pp.58-63
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• 2005

시험물질 산삼배양추출물의 유전독성 평가를 위해 수컷 ICR 마우스 골수세포를 이용한 소핵시험을 실시하였다. 1 회 투여 최고량은 예비 시험에서 결정하였다. 약 7주령의 수컷 마우스에 시험물질 0, 500, 1,000 및 2,000 mg/kg의 용량을 1일 1회 2일간 복강내 투여하고, 최종 투여로부터 약 24시간 후에 골수세포를 수거하여 소핵 유발과 세포독성을 평가하였다. 개체당 2,000개의 다염성적혈구(michromatic erythrocyte, PCE)중에 나타나는 소핵을 가진 다염성적혈구(micronucleated polychromatic erythrocyte, MNPCE)의 수를 계수한 결과, 모든 시험물질 투여군은 음성 대조군에 비해 통계학적으로 유의한 증가는 나타나지 않았으며 일반 증상에서도 모든 시험군은 투여로 인한 것으로 판단되는 증상은 관찰되지 않았다. 부검시 체중에 있어서는 시험물질 최고 용량군에서 유의한 감소가 관찰되었다. 따라서 산삼배양추출물은 위 시험 조건에서, 본 시험에 사용한 마우스 골수세포에 소핵을 유발하지 않는 것으로 사료된다.

• 한국해양바이오학회지
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• 제12권1호
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• pp.20-28
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• 2020

Symbiodinium is a dinoflagellate genus that coexists with coral reefs and is known to provide ultraviolet (UV) protection in nature through the synthesis of mycosporin-like amino acids (MAA). In order to develop a natural and ecofriendly sunblock for use in summer resorts, the possibility of using a Symbiodinium microbiome extract or an MAA was investigated. Two sunblocks, one containing 7% Symbiodinium extract and the other containing MAA were prepared to be tested on hairless mice and human skin. In this clinical study, the sun protection factor (SPF) and Protection factor of UV A (PFA) values of the sunblock containing either Symbiodinium extract or MAA were determined. The SPF values of the sunblock containing Symbiodinium extract and MAA were 10.43 and 10.83, respectively, and the PFA values were 3.42 and 3.39, respectively. Based on their PFA values of ≥2, the UV A protection can be graded as PA+ (low) for both the sunblocks. In addition, the UV-blocking extract of Symbiodinium has a low phototoxicity and cytotoxicity, reducing the possibility of a heavy feeling to the skin or a foreign-body sensation caused by residue build-up. The low toxicity feature of the major sunblock component will also prevent side effects, such as allergic reactions. Although Symbiodinium extract or MAA alone do not provide effectiveprotection against UV irradiation, their protection capacity can be complemented by the addition of inorganic UV-protecting compounds.

• Mass Spectrometry Letters
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• 제3권1호
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• pp.21-24
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• 2012

$5{\alpha}$-Dihydrotestosterone (DHT) is the primary active metabolite of testosterone, catalyzed by $5{\alpha}$-reductase ($5{\alpha}R$) in the skin, prostate, and liver. In this study, the $5{\alpha}R$ activity in rat liver S9 fraction in the presence of a NADPH-generating system was evaluated and compared by gas chromatography-mass spectrometry (GC-MS)-based in vitro assays. Testosterone and a $5{\alpha}R$ inhibitor, finasteride, were added to the S9 fractions and incubated at $37^{\circ}C$ for 1 h. Both testosterone and DHT were quantitatively measured and compared with two different GC-MS-based steroid profiling techniques. DHT was not detected by conventional GC-MS analysis in the absence of finasteride when the concentration of testosterone in the S9 fraction was less than $0.2{\mu}M$, whereas the isotope-dilution GC-MS (GC-IDMS) system was able to evaluate the $5{\alpha}R$ activity. Because the S9 fraction contains more reactive enzymes and is easier to collect from tissues compared with a microsomal solution, the combination of the S9 fraction and GC-IDMS technique may be a promising assay for evaluating the $5{\alpha}R$ activity in large-scale clinical studies.

• 대한약침학회지
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• 제20권2호
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• pp.119-126
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• 2017

Objectives: Semecarpus anacardium Linn. is a plant well-known for its antimicrobial, antidiabetic and anti-arthritic properties in the Ayurvedic and Siddha system of medicine. This has prompted the screening of this plant for antibacterial activity. The main aims of this study were to isolate compounds from the plant's seeds and to evaluate their antibacterial effects on clinical bacterial test strains. Methods: The n-butanolic concentrate of the seed extract was subjected to thin layer chromatography (TLC) and repeated silica gel column chromatography followed by elution with various solvents. The compound was identified based on observed spectral (IR, $^1H$ NMR, $^{13}C$ NMR and high-resolution mass spectrometry) data. The well diffusion method was employed to evaluate the antibacterial activities of the isolated acyclic isoprenoid compound (final concentration: $5-15{\mu}g/mL$) on four test bacterial strains, namely, Staphylococcus aureus (MTCC 96), Bacillus cereus (MTCC 430), Escherichia coli (MTCC 1689) and Acinetobacter baumannii (MTCC 9829). Results: Extensive spectroscopic studies showed the structure of the isolated compound to be an acyclic isoprenoid ($C_{21}H_{32}O$). Moreover, the isoprenoid showed a remarkable inhibition of bacterial growth at a concentration of $15{\mu}g/mL$ compared to the two other doses tested (5 and $10{\mu}g/mL$) and to tetracycline, a commercially available antibiotic that was used as a reference drug. Conclusion: The isolation of an antimicrobial compound from Semecarpus anacardium seeds validates the use of this plant in the treatment of infections. The isolated compound found to be active in this study could be useful for the development of new antimicrobial drugs.

• 한국임상수의학회지
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• 제23권3호
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• pp.366-370
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• 2006

Arachnoid cysts are intra-arachnoid collections of cerebrospinal fluid. They may cause neurological deficit through expansion that can compress normal neural tissue and obstruct cerebrospinal fluid flow. Intracranial arachnoid cysts were found in 4 patients aged 10 months to 20 months(mean age 15 months). The presenting symptoms included circling(dog 2,3), seizure(dog 1), progressive weakness(dog 1,2,3), increasing scoliosis(dog 3), worsening spasticity(dog 3), and salivation(dog 3). One patient showed no symptoms from the intracranial arachnoid cyst. There were no significant findings in complete blood count and serum chemistry. Computed tomography(CT) with/without magnetic resonance imaging(MRI) scans were performed in these cases. Hypodense intracranial arachnoid cyst was observed on CT images in dog 4. Sagittal T1-weighted(T1W) and T2-weighted(T2W) images and transverse T1W and T2W images revealed a intracranial arachnoid cysts with syringohydromyelia(dog 3) and hydrocephalus(dog 3,4) in the brain. Clinical signs of three cases were improved by medication.

• 한국임상수의학회지
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• 제31권2호
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• pp.137-140
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• 2014

말티즈(증례1)와 라브라도 레트리버(증례2)가 요실금 증상으로 내원하였다. 전신상태는 양호하였으며, 혈액혈청검사 및 방사선검사상에서 이상소견은 나타나지 않았다. 증례 1에서는 투시검사, 증례2에서는 컴퓨터 단층촬영을 통해 배설 요로조영검사를 실시하였다. 증례1은 우측 강외성 이소성 요관으로, 증례2는 양측성 강내성 이소성 요관으로 진단되었다. 각각의 증례는 neoureterocytostomy (증례1)와 neoureterostomy (증례2)를 실시하였다. 술후, 3일동안 요관 카테터를 장착하였다. 술후 요실금 증상은 개선되었으며, 다른 임상증상은 나타나지 않았다. 개의 이소성 요관 형태에 따른 적절한 수술법을 통해 이소성 요관을 효과적으로 치료할 수 있었다.

• 한국재료학회지
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• 제17권12호
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• pp.669-675
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• 2007

Hydroxyapatite (HAp) and biphasic calcium phosphate (BCP) nano powders were synthesized using the microwave-assisted synthesis process dependent on pH and microwave irradiation time. The average size of a powder was less than 100 nm in diameter. Through in-vitro cytotoxicity tests by an extract dilution method, the HAp and BCP nano powders have shown to be cytocompatible for L-929 fibroblast cells, osteoblastlike MG-63 cells and osteoclast-like Raw 264.7 cells. The activation of osteoblast was estimated by alkaline phosphatase (ALP) activity. When the HAp and BCP were treated to MG-63 cells, alkaline phosphatase activities increased on day 3, compared with those of the untreated cells. Also, the collagen fibers increased when the HAp and BCP powders suspension were treated to MG-63 cells, compared to those of the untreated cells. Quantitative alizarin red S mineralization assays showed a trend toward increasing mineralization in osteoblast cultured with powder suspension. In conclusion, hydroxyapatite and biphasic calcium phosphate appeared to be a bone graft substitute material with optimal biocompatibility and could be further applied to clinical use as an artificial bone graft substitute.