• Korean Journal of Clinical Pharmacy
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• v.16 no.2
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• pp.155-164
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• 2006

Great inter-variability in drug response and adverse drug reactions is related to inter-variability of drug bioavailability, drug interaction and patient's disease and physyological state that cause change in absorption, distribution, metabolism and excretion of drugs. However, these alone do not sufficiently predict and explain inter-variability in drug response. In recent studies, it is reported that inter-variability in drug response and adverse drug reactions may largely resulted from genetically determined differences in drug absoption, distribution, metabolism and drug target proteins. Especially, the major human drug-metabolizing enzymes such as CYP450, N-acetyl tranferase, thiopurine S-methyl transferase, glutathione S-transferase are identified as the major gene variants that cause inter-individual variability in drug's response and adverse drug reactions. These variations may have most significant implications for those drugs that have narrow therapeutic index and serious adverse drug reactions. Therefore, the genetic variation such as polymorphisms in drug metabolizing enzymes can affect the response of individuals to drugs that are used in the treatment of depression, psychosis, cancer, cardiovascular disorders, ulcer and gastrointestinal disorders, pain and epilepsy, among others. This review describes the pharmacogenomics of the drug metabolizing enzymes associated with the drug response and its clinical applications.

• Genomics & Informatics
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• v.19 no.1
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• pp.10.1-10.7
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• 2021

Although many models have been proposed to accurately predict the response of drugs in cell lines recent years, understanding the genome related to drug response is also the key for completing oncology precision medicine. In this paper, based on the cancer cell line gene expression and the drug response data, we established a reliable and accurate drug response prediction model and found predictor genes for some drugs of interest. To this end, we first performed pre-selection of genes based on the Pearson correlation coefficient and then used ElasticNet regression model for drug response prediction and fine gene selection. To find more reliable set of predictor genes, we performed regression twice for each drug, one with IC₅₀ and the other with area under the curve (AUC) (or activity area). For the 12 drugs we tested, the predictive performance in terms of Pearson correlation coefficient exceeded 0.6 and the highest one was 17-AAG for which Pearson correlation coefficient was 0.811 for IC₅₀ and 0.81 for AUC. We identify common predictor genes for IC₅₀ and AUC, with which the performance was similar to those with genes separately found for IC₅₀ and AUC, but with much smaller number of predictor genes. By using only common predictor genes, the highest performance was AZD6244 (0.8016 for IC₅₀, 0.7945 for AUC) with 321 predictor genes.

• Toxicological Research
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• v.16 no.4
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• pp.269-274
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• 2000

Epoxidised soya bean oil (ESBO, 1000, 2000 or 4000 mg/kg) was orally administered to BALB/c mice daily for 28 consecutive days, and the control mice were exposed to vehicle (corn oil). Mice were immunized and challenged with sheep red blood cells (SRBC) or bovine serum albumin (BSA). In groups exposed to ESBO, the body weight gains and the relative lymphoid organ weights were not significantly changed as compared with control group. Secondary IgG antibody response to BSA was not significantly changed by ESBO, but plaque-forming cell (PFC) response to SRBC was significantly suppressed in mice treated with 4000 mg ESBO/kg/day. The mitogenic response of splenic B cells induced by LPS was not effected by ESBO in any of the groups. These results indicate that ESBO did not induce significant humoral immune response at a dose less than 2000 mg/kg/day in mice.

• YAKHAK HOEJI
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• v.40 no.2
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• pp.230-237
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• 1996

The fractions of Epimedii Herba were examined for the immunological effects in ICR mice. Mice were divided into 4 groups and administered orally the fractions of Epimedii Herba for 10 days. The results of this study were summarized as following: (1) The fraction 1 (EtOAc layer) administered group as compared with control group significantly decreased spleen weight, Arthus reaction and hemagglutination (HA) titer but significantly increased circulating white blood cells (WBC). (2) The fraction 2 ($H_20$ layer) administered group as compared with control group significantly decreased liver weight, Arthus reaction and HA titer but significantly increased WBC. (3) The fraction 3 (ppt) administered group as compared with control group significantly increased liver weight, thymus weight rate, delayed type hypersensitivity, phagocytic activity and WBC. The results showed that Frs. 1 and 2 administered groups reduced humoral immune response but increased WBC, and that Fr. 3 administered group increased cell-mediated immune response, phagocytic activity and WBC.

• Elastomers and Composites
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• v.54 no.2
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• pp.149-155
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• 2019

Controlled mass transport in response to stimuli is essential for drug carriers. The complexity of the signaling system under physiological conditions has led researchers to develop precise nanocontainers that respond to stimuli in the physiological environment. Owing to several reasons, soft nanocontainers such as liposomes and micelles have been investigated for use as drug delivery systems. However, such carriers often suffer from the undesired leakage of drug molecules. In contrast, inorganic nanocontainers are robust, and their surfaces can be easily functionalized. For example, mesoporous silica nanoparticles equipped with gatekeeper molecules are increasingly being used for the controlled release of drug molecules in response to the desired stimuli. Since the development of the first hybrid nanocontainer comprising molecular machines, multiple versions of such gatekeeper systems featuring significantly improved stability and precise response to stimuli have been reported. In this study, various methods for incorporating photoresponsive nanocontainers with porous channels are developed.

• 제어로봇시스템학회:학술대회논문집
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• 2005.06a
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• pp.186-189
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• 2005

In a clinical setting, developing a reliable method for the automated drug infusion system would improve a drug therapy under the unexpected and acute changes of hemodynamics. The conventional proportional-integral-derivative (PID) controller might not be able to achieve maximum performance because of the unexpected change of the intra- and inter-patient variability. The fuzzy PID control and the conventional PID control were tested under the unexpected response of mean arterial blood pressure (MAP) to a vasopressor agent during acute hypotension. Compared with the conventional PID control, the fuzzy PID control performed the robust MAP regulation regardless of the unexpected MAP response (average absolute value of the error between target value and actual MAP: 0.98 vs. 2.93 mmHg in twice response of the expected MAP and 2.59 vs. 9.75 mmHg in three-times response of the expected MAP). The result was due to the adaptive change of the proportional gain in PID parameters.

• Molecules and Cells
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• v.23 no.2
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• pp.123-131
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• 2007

Extracellular stresses induce heat shock response and render cells resistant to lethal stresses. Heat shock response involves induction of heat shock proteins (Hsps). Recently the roles of Hsps in neurodegenerative diseases and cancer are attracting increasing attention and have accelerated the study of heat shock response mechanism. This review focuses on the stress sensing steps, molecules involved in Hsps production, diseases related to Hsp malfunctions, and the potential of proteomics as a tool for understanding the complex signaling pathways relevant to these events.

• BMB Reports
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• v.43 no.12
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• pp.836-841
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• 2010

In the era of personal genomics, predicting the individual response to drug-treatment is a challenge of biomedical research. The aim of this study was to validate whether interaction information between genetic and transcriptional signatures are promising features to predict a drug response. Because drug resistance/susceptibilities result from the complex associations of genetic and transcriptional activities, we predicted the inter-relationships between genetic and transcriptional signatures. With this concept, captured genetic polymorphisms and transcriptional profiles were prepared in cancer samples. By splitting ninety-nine samples into a trial set (n = 30) and a test set (n = 69), the outperformance of relationship-focused model (0.84 of area under the curve in trial set, P = $2.90{\times}10^{-4}$) was presented in the trial set and validated in the test set, respectively. The prediction results of modeling show that considering the relationships between genetic and transcriptional features is an effective approach to determine outcome predictions of drug-treatment.

• YAKHAK HOEJI
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• v.47 no.6
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• pp.356-360
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• 2003

Nitroso-2-naphthol-3,6-disulfonic acid, disodium salt (NRS) was used as an organic ligand to prepare basic drug-selective polymeric membrane electrode. The sensing membrane of the electrode consited of basic drug-meta1(II)-NRS as an ion-exchanger site in a poly(vinyl chloride) matrix plasticized with 2-nitrophenyl octyl ether (NPOE). The metal ions used were Fe$^{2+}$, Co$^{2+}$, Ni$^{2+}$ and Cu$^{2+}$. The electrodes exhibited fast and wide linear response in the basic drug concentration of 10$^{-5}$ ∼10$^{-3}$ mol/l with a response slope of 50∼60 mV/decade in a buffer solution of pH 4∼8. The electrodes exhibited good selectivity for many basic compounds.mpounds.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.276.1-276.1
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• 2002

It is well known that cisplatin. one of chemotherapeutic agents. induces DNA damage and kill cancer cells mainly by apoptosis. We recently synthesized a novel Pt(IV)-based anticancer agent. trans.cis-Pt(acetato)2C12(1.4-butanediamine) (K101) with octahedral structure. To evaluate antitumor activity about human cancer of K101, we have performed histoculture drug response assay in 35 cases of colorectal cancer patients. (omitted)