• Genomics & Informatics
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• v.5 no.2
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• pp.41-45
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• 2007

Pharmacogenomics is the study that examines how genetic variations affect the ways in which people respond to drugs. The ways people respond to drugs are complex traits that are influenced by many different genes. Pharmacogenomics intends to develop rational means of optimizing drug therapy, with respect to the patients' genotype, to maximize efficacy with minimal adverse drug reactions. Pharmacogenomics has the potential to revolutionize the practice of medicine, and promises to usher in an area of personalized medicine, in which drugs and drug combinations are optimized for each individual's unique genetic makeup. Indeed, pharmacogenomics is exploited as an essential step for target discovery and drug development in the pharmaceutical industry. The goal of the personalized medicine is to get the right dose of the right drug to the right patient at the right time. In this article, we will review the use of pharmacogenomics in drug discovery and development.

• Biomolecules & Therapeutics
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• v.26 no.6
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• pp.591-598
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• 2018

Epigenetic silencing is considered to be a major mechanism for loss of activity in tumor suppressors. Reversal of epigenetic silencing by using inhibitors of DNA methyltransferase (DNMT) or histone deacetylases (HDACs) such as 5-Aza-CdR and FK228 has shown to enhance cytotoxic activities of several anticancer agents. This study aims to assess the combinatorial effects of genesilencing reversal agents (5-Aza-CdR and FK228) and oxaliplatin in gastric cancer cells, i.e., Epstein-Barr virus (EBV)-negative SNU-638 and EBV-positive SNU-719 cells. The doublet combinatorial treatment of 5-Aza-CdR and FK228 exhibited synergistic effects in both cell lines, and this was further corroborated by Zta expression induction in SNU-719 cells. Three drug combinations as 5-Aza-CdR/FK228 followed by oxaliplatin, however, resulted in antagonistic effects in both cell lines. Simultaneous treatment with FK228 and oxaliplatin induced synergistic and additive effects in SNU-638 and SNU-719 cells, respectively. Three drug combinations as 5-Aza-CdR prior to FK228/oxaliplatin, however, again resulted in antagonistic effects in both cell lines. This work demonstrated that efficacy of doublet synergistic combination using DNMT or HDACs inhibitors can be compromised by adding the third drug in pre- or post-treatment approach in gastric cancer cells. This implies that the development of clinical trial protocols for triplet combinations using gene-silencing reversal agents should be carefully evaluated in light of their potential antagonistic effects.

• Journal of Food Hygiene and Safety
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• v.26 no.2
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• pp.91-99
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• 2011

Risk ranking must be determined for various hazards/food combinations to conduct microbial risk management effectively. Risk Ranger is a simple, easy-to-use calculation tool developed in Microsoft Excel and designed to rank the risk (low, medium, and high) for semi-quantitative microbial risk assessment. The user is required to answer 11 questions in Risk Ranger related to 1) severity of the hazard, 2) likelihood of a disease-causing dose of the hazard being present in the meal, and 3) the probability of exposure to the hazard in a defined time. This study determined the risk ranking for twenty three combinations of foodborne pathogens/potentially hazardous foods (PHFs) using a Risk Ranger. In this study, pathogenic E. coli in fresh cut produce salad was scored as 79, which was the highest rank among the 23 combinations of the foodborne pathogens and PHFs. On the other hand, zero risk was obtained with V parahaemolyticus in sushi, Salmonella in meat products and E. coli O157:H7 in hamburger patties. Although Risk Ranger is very simple method to rate the risk of foodborne pathogens and PHFs combination, the accuracy of result was mainly affected by the availability and accuracy of data in the literature. According to the result of literature review, the data are needed for contamination rate of raw materials, consumption amount/frequency of PHFs, and the effect of processing on pathogen. Risk ranking must be continuously revalidated with new data.

• Tuberculosis and Respiratory Diseases
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• v.78 no.3
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• pp.161-167
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• 2015

Tuberculosis (TB) remains a major global health problem, and the incidence of TB cases has not significantly decreased over the past decade in Korea. The standard short course regimen is highly effective against TB, but requires multiple TB-specific drugs and a long treatment duration. Recent studies using late-generation fluoroquinolones and/or high-dose rifapentine-containing regimens to shorten the duration of TB treatment showed negative results. Extending the treatment duration may be considered in patients with cavitation on the initial chest radiograph and positivity in sputum culture at 2 months of treatment for preventing TB relapse. Current evidence does not support the use of fixed-dose combinations compared to separate drugs for the purpose of improving treatment outcomes. All patients receiving TB treatment should be monitored regularly for response to therapy, facilitation of treatment completion, and management of adverse drug reactions. Mild adverse effects can be managed with symptomatic therapy and changing the timing of the drug administration, but severe adverse effects require a discontinuation of the offending drugs.

• Biomolecules & Therapeutics
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• v.7 no.2
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• pp.158-163
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• 1999

In order to find less toxic antiherpetic agents, antiviral activities of quercitrin against two strains of pathogenic viruses such as herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) were determined in Vero cells using plaque reduction assay in vitro. Quercitrin showed a concentration-dependent decrease in plaque formation of HSV-1 and HSV-2. It also exhibited more potent antiherpetic activity on HSV-1 with 50% effective concentration (EC$_{50}$) of 20.4 $\mu$g/ml than on HSV-2 with EC$_{50}$ of 30.4 $\mu$g/ml. The combined antiherpetic effects of quercitrin with nucleoside antiherpetic agents, acyclovir and vidarabine, were examined on the multiplication of these two strains of herpesviruses in Vero cells by the combination assay. The results of combination assay were evaluated by the combination index (CI) that was calculated by the multiple drug effect analysis. The combinations of quercitrin with acyclovir and vidarabine on HSV-1 showed more potent synergism with CI values of 0.27-0.81 for 50%, 70%, 90% effective levels than those on HSV-2 with CI values of 1.03~2.20..20.

• Natural Product Sciences
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• v.17 no.2
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• pp.160-164
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• 2011

The purpose of this investigation was to extract the bioactive agents from Alpinia officinarum Hance. The methanol with ethylacetate extracts alone and combined were examined for their activities against VRE (vancomycin-resistant enterococci) and pathogenic yeast in vitro. The incidence of infections caused by VRE and other pathogenic microorganisms and the importance of using novel synergistic drug combinations has become important. Previously, we reported the antimicrobial effects of the butanol extract from Lonicera japonica and have evaluated combinations of solvent extracts, with a focus on the MeOH and EtOAc extracts from A. officinarum. In the present study, enhanced inhibitory effects were achieved by employing a combination of the two solvent extracts. The MeOH and EtOAc combination was especially effective against four VRE strains: E. faecalis (K-10-22), E. faecaium (K-11-212), E. faecalis (K-10-57) and E. faecalis (K-10-361) with MIC values of 12.5, 12.5, 6.25 and 25 ${\mu}g/ml$, respectively. Thus, the combination was more effective than other antibiotics such as kanamycin, gentamicin or tetracycline against bacteria including E. coli, Staphylococcus aureus, and Micrococcus luteus. In addition, the combination was effective against yeasts such as Candida albicans, Candida tropicalis and Cryptococcus neoformans.

• YAKHAK HOEJI
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• v.43 no.1
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• pp.77-84
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• 1999

To search for less toxic antiherpetic agents, the inhibitory effects of natural naringenin on the plaque formation of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in Vero cells were examined by the plaque reduction assay in vitro. Naringenin inhibited plaque formations of HSV-l and HSV-2 in a dose dependent manner. It also exhibited more potent antiherpetic activity on HSV-l with selectivity index (SI) of 19.1 than on HSV-2 with SI of 5.7 The combined antiherpetic effects of naringenin with nucleoside antiherpetic agents, acyclovir and vidarabine, were examined on the multiplication of these two strains of herpesviruses in Vero cells by the combination assay. The results of combination assay were evaluated by the combination index (CI) that was calculated by the multiple drug effect analysis. The combinations of naringenin with acyclovir on HSV-l and HSV-2 showed more potent synergism with CI values of 0.28∼0.81 for 50%, 70%, 90% effective levels than those with vidarabine with CI values of 0.86-3.28.

• Journal of Microbiology and Biotechnology
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• v.17 no.5
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• pp.858-864
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• 2007

This study investigated the antibacterial activities of sophoraflavanone G from Sophora flavescens in combination with two antimicrobial agents against oral bacteria. The combined effect of sophoraflavanone G and the antimicrobial agents was evaluated using the checkerboard method to obtain a fractional inhibitory concentration(FIC) index. The sophoraflavanone G+ampicillin(AM) combination was found to have a synergistic effect against S. mutans, S. sanguinis, S. sobrinus, S. gordonii, A. actinomycetemcomitans, F nucleatum, P. intermedia, and P. gingivalis, whereas the sophoraflavanone G+gentamicin(GM) combination had a synergistic effect against S. sanguinis, S. criceti, S. anginosus, A. actinomycetemcomitans, F nucleatum, P. intermedia, and P. gingivalis. Neither combination exhibited any antagonistic interactions(FIC index>4). In particular, the MICs/MBCs for all the bacteria were reduced to one-half$\sim$one-sixteenth as a result of the drug combinations. A synergistic interaction was also confirmed by time-kill studies for nine bacteria where the checkerboard suggested synergy. Thus, a strong bactericidal effect was exerted through the drug combinations, plus in vitro data suggested that sophoraflavanone G combined with other antibiotics may be microbiologically beneficial rather than antagonistic.

• Tuberculosis and Respiratory Diseases
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• v.77 no.4
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• pp.161-166
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• 2014

Since tuberculosis (TB) remains a major global health concern and the incidence of multi-drug resistant (MDR)-TB is increasing globally, new modalities for the detection of TB and drug resistant TB are needed to improve TB control. The Xpert MTB/RIF test can be a valuable new tool for early detection of TB and rifampicin resistance, with a high sensitivity and specificity. Late-generation fluoroquinolones, levofloxacin, and moxifloxacin, which are the principal drugs for the treatment of MDR-TB, show equally high efficacy and safety. Systemic steroids may reduce the overall TB mortality attributable to all forms of TB across all organ systems, although inhaled corticosteroids can increase the risk of TB development. Although fixed dose combinations were expected to reduce the risk of drug resistance and increase drug compliance, a recent meta-analysis found that they might actually increase the risk of relapse and treatment failure. Regarding treatment duration, patients with cavitation and culture positivity at 2 months of TB treatment may require more than 6 months of standard treatment. New anti-TB drugs, such as linezolid, bedaquiline, and delamanid, could improve the outcomes in drug-resistant TB. Nontuberculous mycobacterial lung disease has typical clinical and immunological phenotypes. Mycobacterial genotyping may predict disease progression, and whole genome sequencing may reveal the transmission of Mycobacterium abscessus. In refractory Mycobacterium avium complex lung disease, a moxifloxacin-containing regimen was expected to improve the treatment outcome.

• Biomolecules & Therapeutics
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• v.26 no.3
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• pp.313-321
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• 2018

Anti-cancer drug resistance is a major problem in colorectal cancer (CRC) research. Although several studies have revealed the mechanism of cancer drug resistance, molecular targets for chemotherapeutic combinations remain elusive. To address this issue, we focused on the expression of cellular prion protein ($PrP^C$) in 5-FU-resistant CRC cells. In 5-FU-resistant CRC cells, $PrP^C$ expression is significantly increased, compared with that in normal CRC cells. In the presence of 5-FU, $PrP^C$ increased CRC cell survival and proliferation by maintaining the activation of the PI3K-Akt signaling pathway and the expression of cell cycle-associated proteins, including cyclin E, CDK2, cyclin D1, and CDK4. In addition, $PrP^C$ inhibited the activation of the stress-associated proteins p38, JNK, and p53. Moreover, after treatment of 5-FU-resistant CRC cells with 5-FU, silencing of $PrP^C$ triggered apoptosis via the activation of caspase-3. These results indicate that $PrP^C$ plays a key role in CRC drug resistance. The novel strategy of combining chemotherapy with $PrP^C$ targeting may yield efficacious treatments of colorectal cancer.