• Fisheries and Aquatic Sciences
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• v.17 no.3
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• pp.305-311
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• 2014

Dieckol is a polyphenol compound isolated from brown algae that has anti-oxidant, anti-inflammatory, and anti-tumor activity. We examined the anti-angiogenic effects of dieckol in endothelial cells under hypoxic conditions. Treatment with $CoCl_2$, a hypoxic mimetic agent, increased proliferation, adhesion, migration, and tube formation in HUVECs, as well as vessel sprouting in rat aortic rings, which correlated well with increased expression of hypoxia-inducible factor 1-alpha ($HIF1{\alpha}$) and ${\beta}1$-integrin. Dieckol suppressed $CoCl_2$-induced adhesion, migration, and tube formation in HUVECs and vessel sprouting in rat aortic rings. Dieckol treatment decreased $CoCl_2$-induced overexpression of $HIF1{\alpha}$ and its downstream signaling molecules, including ${\beta}1$-integrin/Fak, Akt/eNOS, and p38 MAPK. These results suggest that dieckol is a novel angiogenesis inhibitor and a potential treatment for angiogenesis-dependent diseases in humans, such as malignant tumors.

• The Korean Journal of Physiology and Pharmacology
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• v.14 no.5
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• pp.331-336
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• 2010

In rapidly growing tumors, hypoxia commonly develops due to the imbalance between $O_2$ consumption and supply. Hypoxia Inducible Factor (HIF)-$1{\alpha}$ is a transcription factor responsible for tumor growth and angiogenesis in the hypoxic microenvironment; thus, its inhibition is regarded as a promising strategy for cancer therapy. Given that CamKII or PARP inhibitors are emerging anticancer agents, we investigated if they have the potential to be developed as new HIF-$1{\alpha}$-targeting drugs. When treating various cancer cells with the inhibitors, we found that a CamKII inhibitor, KN-62, effectively suppressed HIF-$1{\alpha}$ specifically in hepatoma cells. To examine the effect of KN-62 on HIF-$1{\alpha}$-driven gene expression, we analyzed the EPO-enhancer reporter activity and mRNA levels of HIF-$1{\alpha}$ downstream genes, such as EPO, LOX and CA9. Both the reporter activity and the mRNA expression were repressed by KN-62. We also found that KN-62 suppressed HIF-$1{\alpha}$ by impairing synthesis of HIF-$1{\alpha}$ protein. Based on these results, we propose that KN-62 is a candidate as a HIF-$1{\alpha}$-targeting anticancer agent.

• The Korean Journal of Nuclear Medicine
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• v.35 no.4
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• pp.288-290
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• 2001

A 61 year-old woman underwent perfusion and inhalation lung scan for the evaluation of pulmonary thromboembolism. Tc-99m MAA perfusion lung scan showed multiple round hot spots in both lung fields. Tc-99m DTPA aerosol inhalation lung scan and chest radiography taken at the same time showed normal findings (Fig. 1, 2). A repeated perfusion lung scan taken 24 hours later demonstrated no abnormalities (Fig. 3). Hot spots on perfusion lung scan can be caused by microsphere clumping due to faulty injection technique or by radioactive embolization from upper extremity thrombophlebitis after injection. Focal hot spots can signify zones of atelectasis, where the hot spots probably represent a failure of hypoxic vasoconstriction. Artifactual hot spots due to microsphere clumping usually appear to be round and in peripheral location, and the lesions due to a loss of hypoxic vasoconstriction usually appear to be hot uptakes having linear $borders^{1-3)}$. Although these artifactual hot spots have been well-known, we rarely encounter them. This report presents a case with artifactual hot spots due to microsphere clumping on Tc-99m MAA perfusion lung scan.

• Journal of Pharmaceutical Investigation
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• v.36 no.4
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• pp.231-237
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• 2006

Hypoxia in solid tumors is known to contribute to intrinsic chemoresistance. Histocultures are in vitro 3 dimensional cultures of tumor tissues and maintain the characteristic microenvironment of human solid tumors in vivo including hypoxia and multicellular structure. In this study, we evaluated the pharmacodynamics of tirapazamine(TPZ), a hypoxia-selective cytotoxin, in human non small cell lung cancer(NSCLC) cells grown as monolayers and histocultures. Antiproliferative activity of TPZ was determined after various conditions of drug exposure, and cell cycle arrest and apoptosis were also measured using flow cytometry. In monolayers, hypoxia selectivity measured by hypoxic/normoxic cytotoxicity ratio was increased with longer exposure. Lower cytotoxicity of TPZ was observed in histocultures compared to monolayers, however, a similar level of cytotoxicity was obtained with longer exposure of 96 hr. TPZ induced $G_2/M$ arrest and apoptosis in both culture conditions, which were greatly enhanced under hypoxic condition. Our data clearly showed the different pharmacodynamics of TPZ in monolayers and histocultures. Antiproliferative activity of TPZ against human solid tumors can be improved with longer drug exposure by exploiting drug delivery systems or by combining angiogenesis inhibitors to maintain drug concentration in tumor tissues.

• Proceedings of the Optical Society of Korea Conference
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• 2006.02a
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• pp.359-360
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• 2006

Functional photoacoustic tomography is a new non-invasive imaging modality, and it is emerging as a very practical method for imaging biological tissue structures by means of laser-induced ultrasound. Structures with high optical absorption, such as blood vessels, can be imaged with the spatial resolution of ultrasound, which is not limited by the strong light scattering in biological tissues. By varying wavelengths of the laser light and acquiring photoacoustic images, optical absorption spectrum of each image pixel is found. Since the biochemical constituents of tissues determine the spectrum, useful functional information like oxygen saturation ($SO_2$) and total haemoglobin concentration (HbT) can be extracted. In this study, as a proof-of-principle experiment, hypoxic brain tumor vasculature and traumatic brain injury (TBI) of small animal brain are imaged with functional photoacoustic tomography. High resolution brain vasculature images of oxygen saturation and total hemoglobin concentration are provided to visualize hypoxic tumor vasculature, and hemorrhage on the cortex surface by the TBI.

• Journal of The Korean Dental Society of Anesthesiology
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• v.13 no.3
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• pp.127-131
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• 2013

We experienced failed airway management in a patient who had partial mandibulectomy and reconstruction with free-flap. 40 year-old man (height: 164 cm, body weight: 59 kg) with malignant melanoma on #38 tooth area of mandibular body was scheduled for partial mandibulectomy and reconstruction with free flap. Approximately fifteen-hours after surgery, the patient was extubated without complication. Seven hours after extubation, we experienced respiratory failure andfailed airway managementdue to airway edema and neck. We failed orotracheal intubation with direct laryngoscopy andlaryngeal mask airway, thus we tried tracheostomy but the patient was hypoxic state for more than 30 minutes. The patient had got hypoxic brain damage in whole cerebral cortex and basal ganglia. We should have the policy of airway management of the patients who have massive oro-maxillo-facial surgery and all medical personnel who treat these patients should be educated the policy and airway management methods.

• Molecules and Cells
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• v.21 no.1
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• pp.1-6
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• 2006

Bcl-2/adenovirus E1B 19 kDa-interacting protein 3 (BNIP3) is a mitochondrial pro-apoptotic protein that has a single Bcl-2 homology 3 (BH3) domain and a COOH-terminal transmembrane (TM) domain. Although it belongs to the Bcl-2 family and can heterodimerize with Bcl-2, its pro-apoptotic activity is distinct from those of other members of the Bcl-2 family. For example, cell death mediated by BNIP3 is independent of caspases and shows several characteristics of necrosis. Furthermore, the TM domain, but not the BH3 domain, is required for dimerization, mitochondrial targeting and pro-apoptotic activity. BNIP3 plays an important role in hypoxia-induced death of normal and malignant cells. Its expression is markedly increased in the hypoxic regions of some solid tumors and appears to be regulated by hypoxia-inducible factor (HIF), which binds to a site on the BNIP3 promoter. Silencing, followed by methylation, of the BNIP3 gene occurs in a significant proportion of cancer cases, especially in pancreatic cancers. BNIP3 also has a role in the death of cardiac myocytes in ischemia. Further studies of BNIP3 should provide insight into hypoxic cell death and may contribute to improved treatment of cancers and cardiovascular diseases.

• Molecules and Cells
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• v.37 no.1
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• pp.43-50
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• 2014

Jumonji domain-containing proteins (JMJD) catalyze the oxidative demethylation of a methylated lysine residue of histones by using $O_2$, ${\alpha}$-ketoglutarate, vitamin C, and Fe(II). Several JMJDs are induced by hypoxic stress to compensate their presumed reduction in catalytic activity under hypoxia. In this study, we showed that an H3K27me3 specific histone demethylase, JMJD3 was induced by hypoxia-inducible factor (HIF)-$1{\alpha}/{\beta}$ under hypoxia and that treatment with Clioquinol, a HIF-$1{\alpha}$ activator, increased JMJD3 expression even under normoxia. Chromatin immunoprecipitation (ChIP) analyses showed that both HIF-$1{\alpha}$ and its dimerization partner HIF-$1{\beta}$/Arnt occupied the first intron region of the mouse JMJD3 gene, whereas the HIF-$1{\alpha}/{\beta}$ heterodimer bound to the upstream region of the human JMJD3, indicating that human and mouse JMJD3 have hypoxia-responsive regulatory regions in different locations. This study shows that both mouse and human JMJD3 are induced by HIF-1.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.5 no.1
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• pp.36-47
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• 2019

Hypoxia-inducible factor-1 ($HIF-1{\alpha}$) is a transcription factor activated in response to low oxygen level, and is highly expressed in many solid tumors. Moreover, $HIF-1{\alpha}$ is a representative biomarker of hypoxia and also helps to maintain cell homeostasis under hypoxic condition. Most solid tumors show hypoxia, which induces poor prognosis and resistance to conventional cancer therapies. Thus, early diagnosis of hypoxia with positron emission tomography (PET) radiotracer would be highly beneficial for management of malignant solid tumors with effective cancer therapy. YC-1 is a most promising candidate among several $HIF-1{\alpha}$ inhibitors. As an effort to develop a hypoxia imaging tool as a PET radiotracer, we designed and synthesized [$^{18}F$]DFYC based on potent derivative of YC-1 and performed preliminary in vitro cell uptake study. [$^{18}F$]DFYC showed a significant accumulation in SKBR-3 cells among other cancer cells, proving as a good lead to develop a hypoxic solid tumor such as breast cancer.

• Journal of Ecology and Environment
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• v.43 no.3
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• pp.289-296
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• 2019

We investigated the mortality and the oxidative damages of Deschampsia antarctica in response to waterlogging stress. In field, we compared the changes in the density of D. antarctica tuft at the two different sites over 3 years. The soil water content at site 2 was 6-fold higher than that of site 1, and the density of D. antarctica tuft decreased significantly by 55.4% at site 2 for 3 years, but there was no significant change at site 1. Experimental results in growth chamber showed that the $H_2O_2$ and malondialdehyde content increased under root-flooding treatment (hypoxic conditions-deficiency of $O_2$), but any significant change was not perceptible under the shoot-flooding treatment (anoxic condition-absence of $O_2$). However, total chlorophyll, soluble sugar, protein content, and phenolic compound decreased under the shoot-flooding treatment. In addition, the catalase activity increased significantly on the 1st day of flooding. These results indicate that hypoxic conditions may lead to the overproduction of reactive oxygen species, and anoxic conditions can deplete primary metabolites such as sugars and protein in the leaf tissues of D. antarctica. Under present warming trend in Antarctic Peninsula, D. antarctica tuft growing near the shoreline might more frequently experience flooding due to glacier melting and inundation of seawater, which can enhance the risk of this plant mortality.