• Asian Pacific Journal of Cancer Prevention
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• v.15 no.23
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• pp.10355-10361
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• 2015

Background: MicroRNAs (miRNAs) are small non-coding RNA molecules found in multicellular eukaryotes which are implicated in development of cancer, including cutaneous squamous cell carcinoma (cSCC). Expression is controlled by transcription factors (TFs) that bind to specific DNA sequences, thereby controlling the flow (or transcription) of genetic information from DNA to messenger RNA. Interactions result in biological signal control networks. Materials and Methods: Molecular components involved in cSCC were here assembled at abnormally expressed, related and global levels. Networks at these three levels were constructed with corresponding biological factors in term of interactions between miRNAs and target genes, TFs and miRNAs, and host genes and miRNAs. Up/down regulation or mutation of the factors were considered in the context of the regulation and significant patterns were extracted. Results: Participants of the networks were evaluated based on their expression and regulation of other factors. Sub-networks with two core TFs, TP53 and EIF2C2, as the centers are identified. These share self-adapt feedback regulation in which a mutual restraint exists. Up or down regulation of certain genes and miRNAs are discussed. Some, for example the expression of MMP13, were in line with expectation while others, including FGFR3, need further investigation of their unexpected behavior. Conclusions: The present research suggests that dozens of components, miRNAs, TFs, target genes and host genes included, unite as networks through their regulation to function systematically in human cSCC. Networks built under the currently available sources provide critical signal controlling pathways and frequent patterns. Inappropriate controlling signal flow from abnormal expression of key TFs may push the system into an incontrollable situation and therefore contributes to cSCC development.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.8
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• pp.3711-3719
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• 2016

Drawbacks of conventional cancer treatments, with lack of specificity and cytotoxicity using current approaches, underlies the necessity for development of a novel approach, gene-directed cancer therapy. This has provided novel technological opportunities in vitro and in vivo. This review focuses on a member of an apoptosis inhibitor family, survivin, as a valuable target. Not only the gene but also its promoter are applicable in this context. This article is based on a literature survey, with especial attention to RNA interference as well as tumor-specific promoter action. The search engine and databases utilized were Science direct, PubMed, MEDLINE and Google. In addition to cell-cycle modulation, apoptosis inhibition, interaction in cell-signaling pathways, cancer-selective expression, survivin also may be considered as specific target through its promoter as a novel treatment for cancer. Our purpose in writing this article was to create awareness in researchers, emphasizing relation of survivin gene expression to potential cancer treatment. The principal result and major conclusion of this manuscript are that survivin structure, biological functions and applications of RNA interference systems as well as tumor-specific promoter activity are of major interest for cancer gene therapy.

• Korean Journal of Biological Psychiatry
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• v.22 no.4
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• pp.179-186
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• 2015

Objectives Adrenergic alpha 1 and 2 receptors work as pathways to control the serotonergic neuron moderation and mirtazapine acts as antagonist of these receptors. The adrenoreceptor alpha 1a (ADRA1A) gene, which encodes adrenergic alpha 1 receptor, has Arg-347Cys genetic polymorphism and the polymorphism has strong relationship with many neuro-psychiatric diseases. In this study, we explored the relationship between ADRA1A R347C polymorphism and mirtazapine treatment response in Koreans with major depression. Methods 352 patients enrolled in this study, and the symptoms were evaluated by 17-item Hamilton Depression Rating (HAMD-17) scale. After 1, 2, 4, 8, and 12 weeks of mirtazapine treatment, the association between ADRA1A R347C polymorphism and remission/response outcomes was evaluated. Results Treatment response to mirtazapine was significantly better in T allele carriers than C allele homozygotes after 12 weeks of mirtazapine monotherapy. The percentile decline of HAMD-17 score in T allele carriers was larger than that of C allele homozygotes. ADRA1A R347C genotypes were not significantly associated with remission. Conclusions The result showed that treatment response to mirtazapine was significantly associated with ADRA1A R347C genetic polymorphism. T allele carriers showed better treatment response than C allele homozygotes. It can be supposed that T allele carriers have a trend of better treatment response to mirtazapine monotherapy.

• 한국환경농학회:학술대회논문집
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• 2009.07a
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• pp.93-115
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• 2009

There are growing public concerns over crop and food safeties due to the elevated levels of heavy metals grown in contaminated soil. Heavy metals are classified as the chemical harmful risks for crop and food safety. With implementation of GAP, crop safety is controlled by many regulatory options for soil, irrigation water and fertilizers. Any attempt to retard the metal uptake by crops may be the best protocol to secure crop and food safety. This article reviews the management strategies for heavy metals in view of crop safety in Korea and demonstrates results from the field experiments to retard metal translocation from soil to crops by using chemical amendments and soil layer management methods. Major source of soil pollution by heavy metals has been related with mining activities. Risk assessment revealed that rice consumption and groundwater ingestion in the abandoned mining areas were the major exposure pathways for metals to human and the heavy metal showed the toxic effects on human health. Chemical amendments such as lime and slag retarded Cd uptake by rice (Oryza sativa L.) by increasing soil pH, lowering the phytoavailable Cd concentration in soil solution, immobilizing Cd in soil and converting the available Cd fractions into non-available fractions. The soil layer management methods decreased the Cd uptake by 76% and Pb by 60%. Either reversing the surface layer with subsurface layer or immobilization of metals with layer mixing with lime was considered to be the practical option for the in-situ remediation of the contaminated paddy soils. Combination of chemical soil amendments and layer management methods was efficient to retard the metal bioavailability and thus to secure crop safety for heavy metals. This protocol seems to be cheap, relatively easy to practice and practical in the agricultural fields. However, a long term monitoring work should be followed to verify the efficiency of this protocol.

• Molecular & Cellular Toxicology
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• v.5 no.3
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• pp.179-186
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• 2009

Hexachlorobenzene (HCB) is a bioaccumulative, persistent, and toxic pollutant. HCB is one of the 12 priority of Persistent Organic Pollutants (POPs) intended for global action by the United Nations Environment Program (UNEP) Governing Council. POPs are organic compounds that are resistant to environmental degradation through chemical, biological, and photolytic processes. Some of HCB is ubiquitous in air, water, soil, and biological matrices, as well as in major environmental compartments. HCB has effects on various organs such as thyroid, bone, skin, kidneys and blood cells and especially, revealed strong toxicity to liver. In this study, we identified genes related to hepatotoxiciy induced by HCB in human hepatocellular carcinoma (HepG2) cells using microarray and gene ontology (GO) analysis. Through microarray analysis, we identified 96 up- and 617 down-regulated genes changed by more than 1.5-fold by HCB. And after GO analysis, we determined several key pathways which known as related to hepatotoxicity such as metabolism of xenobiotics by cytochrome P450, complement and coagulation cascades, and tight junction. Thus, our present study suggests that genes expressed by HCB may provide a clue for hepatotoxic mechanism of HCB and gene expression profiling by toxicogenomic analysis also affords promising opportunities to reveal potential new mechanistic markers of toxicity.

• Journal of Gastric Cancer
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• v.2 no.4
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• pp.213-220
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• 2002

Purpose: The cDNA microarray provides a powerful alternative with an unprecedented view in monitoring geneexpression levels and leads to discoveries of regulatory pathways involved in complicated biological processes. Our aim is to explore the different gene-expression patterns in gastric adenocarcinomas. Materials and Methods: By using a cDNA microarray representing 4,600 cDNA clusters, we studied the expression profiling in 10 paired gastric adenocarcinoma samples and in adjacent noncancerous gastric tissues from the same patients. Alterations in the gene-expression levels were confirmed by Vsing Northern blots and reverse-transcription PCR (RT-PCR) in all of 4 randomly selected genes. Results: Genes those were expressed differently in cancer ous and noncancerous tissues were identified. 44 (of which 26 were known) and 92 (of which 43 were known) genes or cDNA were up- and down-regulated, respectively, in more than $80\%$ of the gastric adenocarcinoma samples. In cancer ous tissues, genes related to gene/protein expression, cellcycle regulation, and metabolism were mostly up-regulated whereas genes related to the oncogene/tumor suppressor gene, cell structure/motility, and immunology were mostly down-regulated. The semi-quantitative RT-PCR results for the four genes we tested were consistent with the array findings. Conclusions: These results provide not only a new molecular basis for understanding the biological properties of gastric adenocarcinomas but also a useful resource for future development of therapeutic targets and diagnostic markers for gastric adenocarcinomas.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.1947-1959
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• 2016

Background: Colorectal cancer (CRC) is a major cause of morbidity and mortality, being the second most common type of cancer worldwide in both men and women. It accounts yearly for approximately 9% of all new cases of cancers. Furthermore, the current chemotherapeutic regimens seem unsatisfactory, so that exploration of novel therapeutic modalities is needed. The present study was undertaken to investigate the inhibitory effects of a crude alkaloid extract (CAERS) of a medicinal herb, Rhazya stricta, on proliferation of CRC HCT116 cells and to elucidate mechanisms of action. To achieve these aims, we utilized MTT, comet, DNA laddering and gene reporter assays, along with Western blot and RT-PCR analyses. Results: We found that CAERS inhibited cell proliferation and induced apoptotic cell death in HCT116 cells. Hallmarks of morphological and biochemical signs of apoptosis were clearly evident. CAERS down-regulated DNA-binding and transcriptional activities of NF-${\kappa}B$ and AP-1 proteins, while up-regulating expression of the Nrf-2 protein. It also down-regulated expression levels of the ERK MAPK, Bcl-2, cyclin D1, CDK-4, survivin and VEGF and up-regulated levels of Bax, caspase-3/7 and -9, p53, p21, Nrf-2. Markedly, it promoted mRNA expression levels of cytoprotective genes including the hemeoxygenase-1, NAD(P)H quinine oxidoreductase 1 and UDP-glucuronyltransferase. Conclusions: These findings indicate that CAERS exerts antiproliferative action on CRC cells through induction of apoptotic mechanisms, and suggest CAERS could be a promising agent for studying and developing novel chemotherapeutic agents aimed at novel molecular targets for the treatment of CRC.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.1727-1735
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• 2012

Regardless of advances in treatment modalities with the invention of newer therapies, breast cancer remains a major health problem with respect to its diagnosis, treatment and management. This female malignancy with its tremendous heterogeneous nature is linked to high incidence and mortality rates, especially in developing region of the world. It is the malignancy composed of distinct biological subtypes with diverse clinical, pathological, molecular and genetic features as well as different therapeutic responsiveness and outcomes. This inconsistency can be partially overcome by finding novel molecular markers with biological significance. In recent years, newer technologies help us to indentify distinct biomarkers and increase our understanding of the molecular basis of breast cancer. However, certain issues need to be resolved that limit the application of gene expression profiling to current clinical practice. Despite the complex nature of gene expression patterns of cDNAs in microarrays, there are some innovative regulatory molecules and functional pathways that allow us to predict breast cancer behavior in the clinic and provide new targets for breast cancer treatment. This review describes the landscape of different molecular markers with particular spotlight on vitamin D signaling pathway and apoptotic specific protein of p53 (ASPP) family members in breast cancer.

• Korean Journal of Biological Psychiatry
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• v.5 no.2
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• pp.227-234
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• 1998

Objective : Many evidences suggest that patients with bipolar disorder have functional abnormalities in their postreceptor signal transduction pathways, and mood stabilizing effect of lithium is exerted by modulating this dysfunctioning system. Carbamazepine, an antiepileptic agent, is also known to be effective in the treatment and prevention of bipolar disorder. But the precise mechanism of action of the drug is still poorly understood. This study was performed to elucidate the possible therapeutic mechanism of carbamazepine. Method : The effects of chronic carbamazepine administration on protein kinase A and protein kinase C activities in frontal cortex of rat brain after 2 weeks of drug administration were measured and compared with those of control subjects. Results : Mean(${\pm}SE$) value of activity(phosphate transfer ${\mu}mol/mg$ of $protein{\cdot}min$) of protein kinase A in control and test group was $0.249563{\pm}0.036$ and $0.539853{\pm}0.078$, and that of protein kinase C was $0.654817{\pm}0.053$ and $1.146205{\pm}0.052$ respectively, being increased in test group. And differences between the two groups were statistically significant for both enzymes(protein kinase A ; p<0.01, protein kinase C ; p<0.001). Conclusion : These results show that chronic carbamazepine administration increases protein kinase A and C activities, and concerning the possible mode of therapeutic action in bipolar disorder it is suggested that enhanced enzymes phosphorylate receptor-G-protein-effector complexes to dampen hyperfunctioning neuronal activity and thus stabilize the system.

• Toxicological Research
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• v.6 no.2
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• pp.167-182
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• 1990

Dietary restriction (caloric restriction) is the only intervention which has been reliably shown to extend the maximum life span of warm-blooded animals and delay the many phenomena associated with aging. It is also one of the most effective modulators of toxicity, especially cancer endpoints. In spite of the known modulator effects of caloric restriction, the biological mechanisms responsible for these effects had not been in vestigated until recently. The National Center for Toxicological Research (NCTR), in a collaborative effort with the National Institute of Aging (NIA), initiated a project whereby nine (9) combinations of rodent species/strains and diets were fed both restricted and ad libitum. The NIA's initiative was to identify biomarkers of aging whereas NCTR's initiative was to identify the biological effects associated with the profound effects caloric restriction has in protecting against both spontaneous (age-related) and chemically-induced toxic endpoints. Independent of sex or species, caloric restriction has similar effects on body temperature, oxygen consumption and $CO_2$production. Caloric restriction also decreased lipid glycolysis and metabolism in rats and mice, which suggest decreased production of metabolites which could lead to fatty acid epoxide formation. The age-associated loss of ciradian regulation of intermediate enzymes is also significantly reduced. Moreover, caloric restriction reduced the age-associated feminization of sexually dimorphic liver isozymes, increased several glucocorticoid responsive isozymes, elevated glucagon/insulin ratios, produced less microsomal superoxide and enhanced the capacity for utilzing detoxicating metabolic pathways. Calorically restricted rats have less than half the number of aflatoxin ($AFB_1$)-DNA adducts than ad libitum animals and urinary excretion of $AFB_1$ was increased significantly. Finally, DNA repair mechanisms are enhanced and oncogene expression is decreased in calorically restricted animals.