• Asian Pacific Journal of Cancer Prevention
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• v.16 no.5
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• pp.2031-2035
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• 2015

Intra-tumoral hypoxia is an environment that promotes tumor cell migration, angiogenesis and epithelial-mesenchymal transition that accounts for a major mechanism of metastasis. Chloroquine potentially offers a new therapeutic approach with an 'old' drug for effective and safe cancer therapies, as it exerts anti-metastatic activity. We investigated the inhibitory effect of chloroquine on cholangiocarcinoma (CCA) cell migration under cobalt chloride ($CoCl_2$)-stimulated hypoxia. We showed that chloroquine suppressed CCA cell migration under hypoxic-mimicking conditions on exposure to $100{\mu}M$ $CoCl_2$. Moreover, chloroquine stabilized the protein level of prolyl hydroxylase domain proteins (PHD-2) but reduced the levels of hypoxic responsive proteins such as hypoxia-inducible factor (HIF-$1{\alpha}$) and vascular endothelial growth factor (VEGF). It also suppressed epithelial mesenchymal transition (EMT) by increasing the ratio of E-cadherin to N-cadherin under hypoxic conditions. In conclusion, chloroquine can inhibit hypoxia-stimulated metastasis via HIF-$1{\alpha}$/VEGF/EMT which may serve as a useful additional strategy for CCA therapy.

• Proceedings of the Korea Water Resources Association Conference
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• 2016.05a
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• pp.213-213
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• 2016

수문조사기기의 검정은 수문조사에 활용할 기기를 일관되고 표준화된 기준으로 검사하여 수문조사에 적합한 기기인지 확인하는 것이다. 이러한 검정은 국가수문자료의 신뢰도를 높이고 유지하는 기본적이고 중요한 업무이다. 검정대상기기는 강수량측정기기, 유속측정기기, 수위측정기기, 부유사측정기기, 토양수분측정기기, 증발산량측정기기로 총 6가지이며, 2009년부터 국토교통부 위탁사업으로 한국건설기술연구원(유량조사사업단)에서 수행하고 있다. 특히 유량조사사업단에서는 유속측정기기를 제외한 나머지 5개 수문조사기기에 대해 검정을 수행하고 있다. 연도별로 2009년부터 2015년까지 98대, 334대, 572대, 539대, 359대, 682대, 690대로 총 3,274대를 검정하였고, 관측기종별로 강수량 1,579대, 수위 1,589대 부유사 23대, 토양수분 33대, 증발산량 50대이다. 신청기관별로는 국토교통부(홍수통제소) 1,847대, 환경부(국립환경과학원) 4대, 한국건설기술연구원(유량조사사업단 포함) 81대, K-water 338대, 한국수력원자력(주) 91대, 일반업체 913대에 대한 검정을 실시하였다. 검정을 실시한 강수량측정기기 1,579대 중 보정없이 합격된 기기는 1,495대, 허용오차기준에 미달되어 보정 실시 후 합격한 기기는 76대이며, 불합격 처리된 기기는 8대이다. 수위측정기기는 합격이 1,586대, 기준에 미달되어 불합격된 기기가 2대로 나타났다. 강수량측정기기의 각 연도대비 통계분석 결과 보정률은 2009년 97대 중 8대(8.2%), 2010년 194대 중 3대(1.5%), 2011년 180대 중 24대(13.3%), 2012년 175대 중 17대(9.7%), 2013년 165대 중 15대(9.1%), 2014년 547대 중 8대(1.5%), 2015년 221대 중 9대(4.1%)로 다소 낮은 수치로 나타났다. 이처럼 보정률이 낮게 나타난 이유는 관할기관의 검정을 위한 유지관리 및 사업자의 사전검사 등을 통해 감소한 것으로 판단되며, 이와 같은 결과는 수문자료의 품질 및 신뢰도 향상으로 이어졌다. 그러나 여전히 선진국에 비해 수문조사기기 검정의 중요성에 대한 인프라 구축이 미흡한 실정이다. 수문조사기기 검정의 선진국이라 할 수 있는 미국의 경우 USGS에서 HIF(Hydrogical Istrumentation Facility)라는 별도 조직을 운영하여 관측기기의 렌탈, 수리, 교정 및 검정, 개발, 교육 등 이러한 작업을 일괄 수행하고 있고 조직 내 자체 시설로 수중펌프 시험소, 자연과 유사한 환경에서 테스트 하는 장소, 대형온도챔버 등을 갖추고 있으며, 이러한 시설을 이용하여 기기의 교정 및 검정, 연구 등을 현장과 비슷한 환경에서 다양한 실험을 통해 검정방법을 비교, 분석하는 것을 볼 수 있다. 현재 우리나라의 수문조사기기는 다양한 방법으로 현장에 설치되어 검정방법의 다양성이 요구된다. 향후 우리나라도 HIF와 같이 다양하고 선진화된 시설과 기술을 개선하고 다각적인 시험 과정을 통해 수준 높은 검정방법체계를 갖추려는 노력이 필요하다.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3675-3680
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• 2012

Objective: To investigate the expression of endogenous hypoxia-related markers identified as being involved in vulvar squamous cell carcinoma (VSCC). Methods: We performed immunohistochemical staining of hypoxia-inducible factor-$1{\alpha}$ (HIF-$1{\alpha}$), glucose transporter-1 (GLUT-1), carbonic anhydrase 9 (CA-9) and vascular endothelial growth factor (VEGF), on tissue sections of 25 VSCC patients, 10 vulvar intraepithelial neoplasia (VIN) patients and 12 healthy controls. Results: HIF-$1{\alpha}$ expression was found in all sections, with no significant difference between controls, VIN and VSCC sections (all P<0.05). Glut-1 expression was found in 25% of control, 90% of VIN and 100% of VSCC sections. A significant difference between control and VIN or VSCC was observed (all P<0.05), while no difference was found between VIN and VSCC sections (P>0.05). CA-9 expression was negative in control sections, but it was found in 30% of VIN sections and 52% of VSCC sections with strong staining. Similarly, CA-9 expression also showed obvious differences between controls and VIN or VSCC sections (all P<0.05). However, there was no significant difference between VIN and VSCC (P>0.05). There were only 25% of control sections with weak VEGF expression, while strong staining was found in about 60% of VIN sections and 25% of VSCC sections (all P<0.05). In addition, a difference was also found between VIN and VSCC sections (P<0.05). Conclusion: Expression of endogenous hypoxia markers (HIF-$1{\alpha}$, GLUT-1, CA-9 and VEGF) might be involved in the malignant progression of VSCC.

• Proceedings of the Korean Society of Toxicology Conference
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• 2001.10a
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• pp.187-187
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• 2001

Since hypoxia-inducible factor-lalpha (HIF-lalpha) and the arylhydrocarbon receptor (AhR) shared the AhR nuclear translocator (Arnt) for hypoxia- and AhR-mediated signaling, respectively, it was possible to establish the hypothesis that hypoxia could regulate Cyp1a1 expression.(omitted)

• Journal of Life Science
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• v.14 no.1
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• pp.26-31
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• 2004

Redox factor-1 (Ref-1), known as a redox regulator, controls the DNA binding of AP-1 and is activated in HT29 colon cancer cells by hypoxia in vitro. REF-1 also increases tile DNA binding affinity of Hypoxia-inducible Factor-lalpha$ (HIF-lalpha$), HIF-like Factor (HLF) and early growth response-1 (Egr-1) which induce expression of the genes involved in angiogenesis, so that we speculate that REF-1 may play a role in hypoxia-induced angiogenesis. In this research we tried to detect novel proteins interacting with REF-1 using Yeast two-hybrid system using full-length REF-1 cDNA as bait. As result of such screening we detected 3 positive clones. DNA sequencing and GeneBank search revealed that one of the clones contained the same sequences as M.musculus cDNA for tioredoxin.

• Journal of Ginseng Research
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• v.46 no.6
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• pp.738-749
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• 2022

Background: Ginseng possesses antitumor effects, and ginsenosides are considered to be one of its main active chemical components. Ginsenosides can further be hydrolyzed to generate secondary saponins, and 20(R)-panaxotriol is an important sapogenin of ginsenosides. We aimed to synthesize a new ginsengenin derivative from 20(R)-panaxotriol and investigate its antitumor activity in vivo and in vitro. Methods: Here, 20(R)-panaxotriol was selected as a precursor and was modified into its derivatives. The new products were characterized by ¹H-NMR, ¹³C-NMR and HR-MS and evaluated by molecular docking, MTT, luciferase reporter assay, western blotting, immunofluorescent staining, colony formation assay, EdU labeling and immunofluorescence, apoptosis assay, cells migration assay, transwell assay and in vivo antitumor activity assay. Results: The derivative with the best antitumor activity was identified as 6,12-dihydroxy-4,4,8,10,14-pentamethyl-17-(2,6,6-trimethyltetrahydro-2H-pyran-2-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl(tert-butoxycarbonyl)glycinate (A11). The focus of this research was on the antitumor activity of the derivatives. The efficacy of the derivative A11 (IC₅₀ < 0.3 µM) was more than 100 times higher than that of 20(R)- panaxotriol (IC₅₀ > 30 µM). In addition, A11 inhibited the protein expression and nuclear accumulation of the hypoxia-inducible factor HIF-1α in HeLa cells under hypoxic conditions in a dose-dependent manner. Moreover, A11 dose-dependently inhibited the proliferation, migration, and invasion of HeLa cells, while promoting their apoptosis. Notably, the inhibition by A11 was more significant than that by 20(R)-panaxotriol (p < 0.01) in vivo. Conclusion: To our knowledge, this is the first study to report the production of derivative A11 from 20(R)-panaxotriol and its superior antitumor activity compared to its precursor. Moreover, derivative A11 can be used to further study and develop novel antitumor drugs.

• The Korean Journal of Physiology and Pharmacology
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• v.13 no.3
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• pp.257-263
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• 2009

This study aimed to investigate whether selective serotonin reuptake inhibitors (SSRIs) attenuate brain injury and facilitate recovery following photothrombotic cortical ischemia in mice. Male ICR mice were anesthetized and systemically administered Rose Bengal. Permanent focal ischemia was induced in the medial frontal and somatosensory cortices by irradiating the skull with cold light laser. The animals were treated with fluoxetine or sertraline once a day for 14 d starting 1 h after ischemic insult. Treatment with fluoxetine and sertraline significantly reduced the infarct size. The Evans blue extravasation indices of the fluoxetine- and sertraline-treated groups were significantly lower than that of the vehicle group. Treatment with fluoxetine and sertraline shifted the lower limit of the mean arterial blood pressure for cerebral blood flow autoregulation toward normal, and significantly increased the expression of heme oxygenase-1 (HO-1) and hypoxia-inducible factor-1 ${\alpha}$ (HIF-1 ${\alpha}$) proteins in the ischemic region. These results suggest that SSRIs, such as fluoxetine and sertraline, facilitate recovery following photothrombotic cortical ischemia via enhancement of HO-1 and HIF-1 ${\alpha}$ proteins expression, thereby providing a benefit in therapy of cerebral ischemia.

• Archives of Plastic Surgery
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• v.42 no.1
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• pp.59-67
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• 2015

Background Negative-pressure wound therapy (NPWT) induces angiogenesis and collagen synthesis to promote tissue healing. Although acetic acid soaks normalize alkali wound conditions to raise tissue oxygen saturation and deconstruct the biofilms of chronic wounds, frequent dressing changes are required. Methods Combined use of NPWT and acetic acid irrigation was assessed in the treatment of chronic wounds, instilling acetic acid solution (1%) beneath polyurethane membranes twice daily for three weeks under continuous pressure (125 mm Hg). Clinical photographs, pH levels, cultures, and debrided fragments of wounds were obtained pre- and posttreatment. Tissue immunostaining (CD31, Ki-67, and CD45) and reverse transcription-polymerase chain reaction (vascular endothelial growth factor [VEGF], vascular endothelial growth factor receptor [VEGFR]; procollagen; hypoxia-inducible factor 1 alpha [HIF-1-alpha]; matrix metalloproteinase [MMP]-1,-3,-9; and tissue inhibitor of metalloproteinase [TIMP]) were also performed. Results Wound sizes tended to diminish with the combined therapy, accompanied by drops in wound pH (weakly acidic or neutral) and less evidence of infection. CD31 and Ki-67 immunostaining increased (P<0.05) post-treatment, as did the levels of VEGFR, procollagen, and MMP-1 (P<0.05), whereas the VEGF, HIF-1-alpha, and MMP-9/TIMP levels declined (P<0.05). Conclusions By combining acetic acid irrigation with negative-pressure dressings, both the pH and the size of chronic wounds can be reduced and infections be controlled. This approach may enhance angiogenesis and collagen synthesis in wounds, restoring the extracellular matrix.

• Journal of Gastric Cancer
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• v.22 no.2
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• pp.156-156
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• 2022

• Journal of Microbiology and Biotechnology
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• v.29 no.7
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• pp.1155-1164
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• 2019

Lichens contain diverse bioactive secondary metabolites with various chemical and biological properties, which have been widely studied. However, details of the inhibitory mechanisms of their secondary metabolites against influenza A virus (IAV) have not been documented. Here, we investigated the antiviral effect of lichen extracts, obtained from South Korea, against IAV in MDCK cells. Of the lichens tested, Nipponoparmelia laevior (LC24) exhibited the most potent inhibitory effect against IAV infection. LC24 extract significantly increased cell viability, and reduced apoptosis in IAV-infected cells. The LC24 extract also markedly reduced (~ 3.2 log-fold) IAV mRNA expression after 48 h of infection. To understand the antiviral mechanism of LC24 against IAV, proteomic (UPLC-$HDMS^E$) analysis was performed to compare proteome modulation in IAV-infected (V) vs. mock (M) and LC24+IAV (LCV) vs. V cells. Based on Ingenuity Pathway Analysis (IPA), LC24 inhibited IAV infection by modulating several antiviral-related genes and proteins (HSPA4, HSPA5, HSPA8, ANXA1, ANXA2, $HIF-1{\alpha}$, AKT1, MX1, HNRNPH1, HNRNPDL, PDIA3, and VCP) via different signaling pathways, including $HIF-1{\alpha}$ signaling, unfolded protein response, and interferon signaling. These molecules were identified as the specific biomarkers for controlling IAV in vitro and further confirmation of their potential against IAV in vivo is required. Our findings provide a platform for further studies on the application of lichen extracts against IAV.