• Biomedical Science Letters
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• v.23 no.1
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• pp.1-7
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• 2017

It is known that acute myeloid leukemia (AML) is a heterogeneous blood cancer, which is enormously propagated by self-renewing leukemia stem cells (LSCs). The persistence of LSCs after chemotherapy can contribute to minimal residual disease and relapse by LSCs can be evoked promptly. Elucidating special molecules and cellular activity of LSCs is an extremely important to eliminate AML. Despite an increasing understanding of the origin of LSCs by incessant study, AML still remains a notorious disease with high mortality. An exact identification of the LSCs that sustain the proliferation of neoplastic clone is a fundamental issue in AML treatment. CD34+CD38- conventional phenotype is overall regarded as LSCs, but it has a limitation that is still hard to demarcate exactly due to similarity with normal hematopoietic stem cells (HSCs). Not all primary blasts and progenitors have equal function, thus a bona fide marker for identifying LSCs from HSCs is needed in hematologic malignancy, especially in AML. These findings have direct important implications in both in mechanistic study of LSCs as well as in the strategies of more effective therapies. In this review, I briefly summarized current advances in LSCs biology, focusing on membrane markers and a functional behavior of LSCs in AML treatment with monoclonal antibodies. Ultimately, it may be helpful in overviewing the status of LSC research, while expecting the clinic benefits of target therapy by specific inhibition.

• Biomedical Science Letters
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• v.22 no.2
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• pp.46-52
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• 2016

Salicornia herbacea L. (S. herbacea) is an annual herbaceous plant of Chenopodiaceae. It grows in groups on the coast or mud flat of Korea is known to be rich in minerals. S. herbacea has potent anti-cancer, antioxidant, anti-obesity, bowel function improvement. However, pharmacological mechanisms of S. herbacea extract (SHE) remain poorly understood. The aim of this study was to investigate the potential acute toxicity of SHE in ICR mice administered a single oral dose of 0, 500, 1,000, and 2,000 mg/kg by gavage. After administration of the extract, signs of toxicity were observed every day for 14 days. No mortality, abnormal clinical signs, body weight, organ weight or pathological changes were observed compared to a control group, and there were no differences in the body weights of the control and treatment groups. Biological serum activities and histological tests were not significantly changed in the treatment group compared to the control group. Especially, treatment of SHE was significantly decreased of total cholesterol and triglyceride levels. These results indicated that a single oral administration of SHE does not exerts any toxic effects at a dose of 2,000 mg/kg and that the $LD_{50}$ of SHE is greater than 2,000 mg/kg. Accordingly, SHE appears to have potential in various functional agents of foods, without toxicity.

• The Korean Journal of Physiology and Pharmacology
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• v.5 no.4
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• pp.323-331
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• 2001

A splanchic artery occlusion for 90 min followed by reperfusion of the mesenteric circulation resulted in a severe form of circulatory shock characterized by endothelial dysfunction, severe hypotension, marked intestinal tissue injury, and a high mortality rate. The effect of rutin, a flavonoid having antiprostanoid, anti-inflammatory, antithrombotic, antioxidant effect, were investigated in a model of splanchnic artery occlusion (SAO) shock in urethane anesthetized rats. Occlusion of the superior mesenteric artery for 90 min produced a severe shock state resulted in a fatal outcome within 120 min of reperfusion in many rats. Rutin was given as a bolus (1.28 mg/kg) 10 min prior to reperfusion. Administration of rutin significantly improved mean arterial blood pressure in comparison to vehicle treated rats (p＜0.05). Rutin treatment also resulted in a significant attenuation in the increase in plasma amino nitrogen concentration, intestinal myeloperoxidase activity, intestinal lipid peroxidation, infiltration of neutrophils in intestine and thrombin induced adherence of neutrophils to superior mesentric artery segments. These results suggest that rutin provides beneficial effects in part by preserving endothelial function and attenuating neutrophil accumulation in the ischemic reperfused splanchnic circulation.

• IMMUNE NETWORK
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• v.15 no.4
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• pp.206-211
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• 2015

Pulmonary edema is a major cause of mortality due to acute lung injury (ALI). The involvement of protein kinase C-${\delta}$ (PKC-${\delta}$) in ALI has been a controversial topic. Here we investigated PKC-${\delta}$ function in ALI using PKC-${\delta}$ knockout (KO) mice and PKC inhibitors. Our results indicated that although the ability to produce proinflammatory mediators in response to LPS injury in PKC-${\delta}$ KO mice was similar to that of control mice, they showed enhanced recruitment of neutrophils to the lung and more severe pulmonary edema. PKC-${\delta}$ inhibition promoted barrier dysfunction in an endothelial cell layer in vitro, and administration of a PKC-${\delta}$-specific inhibitor significantly increased steady state vascular permeability. A neutrophil transmigration assay indicated that the PKC-${\delta}$ inhibition increased neutrophil transmigration through an endothelial monolayer. This suggests that PKC-${\delta}$ inhibition induces structural changes in endothelial cells, allowing extravasation of proteins and neutrophils.

• Journal of Chest Surgery
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• v.24 no.2
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• pp.153-160
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• 1991

Tetralogy of Fallot was repaired by a transatrial-transpulmonary approach in 91 of 250 patients treated surgically [including redo operations] between April 1986 and December 1989. Their age ranged from 6 months to 14 years [mean 39.7 months]. Associated cardiovascular anomalies were right aortic arch [n=22], ASD [n=12], PDA [n=5], persistent left SVC [n=5], and others [n=6]. PA index was measured pre-operatively since 1987 to estimate pulmonary artery size and safe total correction[mean 289$\pm$110mm2/BSA]. Eight patients received previous shunt take down procedure concomitantly. Pulmonary arteriotomy was extended through small pulmonary annulus to a minimal distance upon the right ventricular infundibulum and transannular patch was applied in 38 patients [41.3%], in 31 of them monocuspid patch was utilized. pRV/LV was measured at operation room in 77 patients [mean 0.58$\pm$0.36]. Operative mortality was 6.6% [6/91]. The causes of death were low cardiac output [n=5], arrhythmia[n=1] and respiratory failure [n=1]. At follow-up between 12 months and 57 months [mean 30.8 months] most patients were in New York Heart Association class I without cardiac medication. There was no late death, but reoperations were required in 3 patients to relieve residual right ventricular outflow obstruction. Thus successful repair of tetralogy of Fallot can be accomplished in most patients including infants by transatrial-transpulmonary approach and the better result can be anticipated with respect to postoperative right ventricular function and arrhythmia than the conventional transventricular approach.

• Toxicological Research
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• v.17
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• pp.299-304
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• 2001

Xenobiotics and their reactive intermediates bind to cellular macromolecules and/or generate oxidative stress. which provoke deleterious effects on the cell function. Induction of xenobiotic-biotrans-forming enzymes and antioxidant molecules is an important defense mechanism against such insults. A group of genes involved in the defense mechanism. e.g. genes encoding glutathione S-transferases. NAD(P)H: quinone oxidoreductase, UDP-glucuronosyltransferase (UDP-GT) and ${\gamma}$-glutamylcysteine synthetase (GGCS). have a common regulatory sequence, Antioxidant or Electrophile Responsive Element (ARE/EpRE). Recently. Nrf2. discovered as a homologue of erythroid transcription factor p45 NF-E2, was shown to bind ARE/EpRE and induce the expression of these defense genes. Mice that lack Nrf2 show low basal levels of expression and/or impaired induction of these genes. which makes the animals highly sensitive to xenobiotic toxicity. Indeed. we show here that nrf2-deficient mice had a higher mortality than did the wild-type mice when exposed to acetaminophen (APAP). Detailed analyses of APAP hepatotoxicity in the nrf2 knockout mice indicate that a large amount of reactive APAP metabolites was generated in the livers due to the impaired basal expression of two detoxifying enzyme genes, UDP-GT (Ugt1a6) and GGCS. while the cytochrome P450 content was unchanged. Thus. the studies using the nrf2 knockout mice clearly demonstrate significance of the expression of Nrf2-regulated enzymes in protection against xenobiotic toxicity.

• Journal of Animal Science and Technology
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• v.58 no.5
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• pp.18.1-18.10
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• 2016

Muscle, studied mostly with respect to meat production, represents one of the largest protein reservoirs of the body. As gene expression profiling holds credibility to deal with the increasing demand of food from animal sources, excessive loss due to myopathies and other muscular dystrophies was found detrimental as it aggravates diseases that result in increased morbidity and mortality. Holding key point towards improving the developmental program of muscle in meat producing animals, elucidating the underlying mechanisms of the associated pathways in livestock animals is believed to open up new avenues towards enhancing the lean tissue deposition. To this end, identification of vital candidate genes having no known function in myogenesis, is believed to increase the current understanding of the physiological processes going on in the skeletal muscle tissue. Taking consequences of gene expression changes into account, knowledge of the pathways associated with their activation and as such up-regulation seems critical for the overall muscle homeostasis. Having important implications on livestock production, a thorough understanding of postnatal muscle development seems a timely step to fulfil the growing need of ever increasing populations of the world.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.18
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• pp.8599-8604
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• 2016

Ovarian cancer is the main cause of mortality in gynecological malignancy and extensive studies have been conducted to study the underlying molecular mechanisms. The BRCA2 gene is known to be an important tumor suppressor in ovarian cancer, thereby BRCA2 alterations may lead to cancer progression. However, the BRCA2 gene is rarely mutated, and loss of function is suspected to be mediated by epigenetic regulation. In this study we investigated the methylation status and gene expression of BRCA2 in ovarian cancer patients. Ovarian cancer pateints (n=69) were recruited and monitored for 54 months in this prospective cohort study. Clinical specimens were used to study the in situ expression of aberrant BRCA2 proteins and the methylation status of BRCA2. These parameters were then compared with clinical parameters and overall survival rate. We found that BRCA2 methylation was found in the majority of cases (98.7%). However, the methylation status was not associated with protein level expression of BRCA2 (49.3%). Therefore in addition to DNA methylation, other epigenetic mechanisms may regulate BRCA2 expresison. Our findings may become evidence of BRCA2 inactivation mechanism through DNA methylation in the Indonesian population. More importantly, from multivariate analysis, BRCA2 expression was correlated with better overall survival (HR 0.32; p=0.05). High percentage of BRCA2 methylation and correlation of BRCA2 expression with overall survival in epithelial ovarian cancer cases may lead to development of treatment modalities specifically to target methylation of BRCA genes.

• Korean Journal of Biological Psychiatry
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• v.13 no.2
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• pp.59-69
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• 2006

Bidirectional relationships exist between cancer and depression; the prevalence of depression in cancer patients is higher than in the general population, and depression predicts cancer progression and mortality. The mechanisms through which depression contributes to the progression of cancer are related with dysregulation of the hypothalamic-pituitary-adrenal axis and impairment of immune function. However, depression in cancer patients tends to be underdiagnosed and not appropriately treated. The methods of diagnosis and assessment of depression in cancer patents have been debated because physical symptoms of depression mimic both cancer symptoms per se and the side effects of cancer treatment. Many studies have shown that various psychosocial and/or pharmacological interventions are effective at improving de-pressive symptoms and quality of life in cancer patients. Furthermore, antidepressant treatments are effective for various physical symptoms related to cancer, such as fatigue, anorexia, pain, hot flashes, and itching. This article reviews and discusses current knowledge about depression in cancer patients.

• Journal of Chest Surgery
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• v.35 no.7
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• pp.560-563
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• 2002

Unilateral diaphragmatic paralysis due to a phrenic nerve injury is not rare after cardiothoracic surgery and may range from an asymptomatic radiographic abnormality to severe pulmonary dysfunction and even mortality in patients with reduced lung function. The most effective treatment for symptomatic unilateral diaphragmatic paralysis has been known to be a plication of the paralyzed hemidiaphragm. A 38 year-old male patient with asthma received a phrenic nerve reconstruction with a sural nerve for right phrenic nerve injury during resection of the anterior mediastinal tumor. Ten months later, chest PA showed good result and we report this case with literature.