• Tuberculosis and Respiratory Diseases
• /
• 제67권4호
• /
• pp.325-330
• /
• 2009

Background: Pulmonary tuberculosis (TB) is still common disease among the elderly patients in Korea where the overall incidence of TB is decreasing. Adverse drug reactions (ADR) associated with anti-TB drugs occurs frequently. Especially the aged tends to have more frequent ADRs than younger ones. These ADRs can cause significant morbidity, compromise therapeutic effects of drugs and even induce drug resistance. Therefore we evaluated the effect of ADRs on the first-line anti-TB drugs in elderly patients with active pulmonary TB. Methods: We retrospectively reviewed the charts and radiological findings of the patients with 65 and older who were bacteriologically confirmed as active TB and treated with standard anti-TB drugs for at least 6 months. Major ADR was defined with temporary or continuous stop of any first-line drugs intake. Results: An ADR was noted in 54% of all patients. The incidence of major ADR was 32% in all elderly patients. Dermatologic ADR (9%) was the most common among the major ADRs. GI trouble (8%), arthralgia (6%), visual change (6%), hepatotoxicity (4%), and fever (1%) were also noted. The drugs responsible for major ADR were ethambutol (62%), pyrazinamide (35%), rifampin (18%) and isoniazid (9%). Major ADRs were associated with higher ESR level at the initiation of anti-TB drugs. Conclusion: First-line anti-TB drugs in elderly patients frequently caused the major ADRs. Therefore the elderly patients receiving anti-TB drugs should be closely monitored and better tolerable therapy should be considered as part of a TB research agenda.

• Nutrition Research and Practice
• /
• 제6권3호
• /
• pp.201-207
• /
• 2012

This study investigated the hypoglycemic, hypolipidemic, and antioxidant effects of dietary quercetin in an animal model of type 2 diabetes mellitus. Four-week-old C57BL/KsJ-db/db mice (n = 18) were offered an AIN-93G diet or a diet containing quercetin at 0.04% (low quercetin, LQE) or 0.08% of the diet (high quercetin, HQE) for 6 weeks after 1 week of adaptation. Plasma glucose, insulin, adiponectin, and lipid profiles, and lipid peroxidation of the liver were determined. Plasma glucose levels were significantly lower in the LQE group than in the control group, and those in the HQE group were even further reduced compared with the LQE group. The homeostasis model assessment for insulin resistance (HOMA-IR) showed lower values for LQE and HQE than for the control group without significant influence on insulin levels. High quercetin increased plasma adiponectin compared with the control group. Plasma triglycerides in the LQE and HQE groups were lower than those in the control group. Supplementation with high quercetin decreased plasma total cholesterol and increased HDL-cholesterol compared with the control group. Consumption of low and high quercetin reduced thiobarbituric acid reactive substances (TBARS) levels and elevated activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in the liver. Thus, quercetin could be effective in improving hyperglycemia, dyslipidemia, and antioxidant status in type 2 diabetes.

• Toxicological Research
• /
• 제33권1호
• /
• pp.1-5
• /
• 2017

Nuclear factor E2-related factor 2 (Nrf2), a transcription factor, controls the expression of genes encoding cytoprotective proteins, including antioxidant enzymes that combat oxidative and electrophilic stress to maintain redox homeostasis. However, recent studies demonstrated that, in cancer, aberrant activation of Nrf2 by epigenetic alterations promotes high expression of cytoprotective proteins, which can decrease the efficacy of anticancer drugs used for chemotherapy. In this review, we summarize recent findings regarding the relationship between oxidative stress, Nrf2, epigenetic modification, and anticancer drug resistance, which should aid in development of new strategies to improve chemotherapeutic efficacy.

• BMB Reports
• /
• 제49권4호
• /
• pp.238-243
• /
• 2016

The efficacy of anticancer drugs depends on a variety of signaling pathways, which can be positively or negatively regulated. In this study, we show that SETDB1 HMTase is down-regulated at the transcriptional level by several anticancer drugs, due to its inherent instability. Using RNA sequence analysis, we identified FosB as being regulated by SETDB1 during anticancer drug therapy. FosB expression was increased by treatment with doxorubicin, taxol and siSETDB1. Moreover, FosB was associated with an increased rate of proliferation. Combinatory transfection of siFosB and siSETDB1 was slightly increased compared to transfection of siFosB. Furthermore, FosB was regulated by multiple kinase pathways. ChIP analysis showed that SETDB1 and H3K9me3 interact with a specific region of the FosB promoter. These results suggest that SETDB1-mediated FosB expression is a common molecular phenomenon, and might be a novel pathway responsible for the increase in cell proliferation that frequently occurs during anticancer drug therapy.

• 한국축산식품학회지
• /
• 제39권5호
• /
• pp.687-703
• /
• 2019

A survey we conducted suggests that the ingestion of veterinary drug residues in edible animal parts constitutes a potential health hazard for its consumers, including, specifically, the possibility of developing multidrug resistance, carcinogenicity, and disruption of intestinal normal microflora. The survey results indicated that antibiotics, parasitic drugs, anticoccidial, or nonsteroidal anti-inflammatory drugs (NSAIDs) are broadly used, and this use in livestock is associated with the appearance of residues in various animal products such as milk, meat, and eggs. We observed that different cooking procedures, heating temperatures, storage times, fermentation, and pH have the potential to decrease drug residues in animal products. Several studies have reported the use of thermal treatments and sterilization to decrease the quantity of antibiotics such as tetracycline, oxytetracycline, macrolides, and sulfonamides, in animal products. Fermentation treatments also decreased levels of penicillin and pesticides such as dimethoate, malathion, Dichlorodiphenyldichloroethylene, and lindane. pH, known to influence decreases in cloxacillin and oxacillin levels, reportedly enhanced the dissolution of antimicrobial drug residues. Pressure cooking also reduced aldrin, dieldrin, and endosulfan in animal products. Therefore, this review provides updated information on the control of drug residues in animal products, which is of significance to veterinarians, livestock producers, and consumer health.

• 공업화학
• /
• 제22권2호
• /
• pp.119-124
• /
• 2011

현재, 사람들은 많은 병에 노출되어 있다. 산업화의 빠른 변화는 생산시설의 자동화, 정보 통신 산업기술의 발달로 삶의 질이 향상되었으나, 신체활동의 감소와 환경오염으로 인해 환경적 스트레스와 병원균 감염 반응에 대한 인간의 면역체계가 악화되었다. 아울러 현재 약물의 오 남용으로 다재약물내성을 갖는 미생물들(multidrug-resistant microbes)과 암세포(tumor)의 출현으로 인해 새로운 항생제 개발이 시급하다. 그들 중 하나가 항생 펩타이드(antibiotic peptide)로 기존 약물과 비교하면 약물저항성이 거의 일어나지 않는다. 여러 가지 항생활성을 가지는 펩타이드들은 다양한 생명체로부터 동정되고 있다. 이 논문은 항생 펩타이드들의 활성과 적용분야에 대해 논하려 한다.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권6호
• /
• pp.2911-2916
• /
• 2014

Oxaliplatin is a first-line therapy for colorectal cancer, but cancer cell resistance to the drug compromises its efficacy. To explore mechanisms of drug resistance, we treated colorectal cancer cells (HCT116 and SW620) long-term with oxaliplatin and established stable oxaliplatin-resistant lines (HCT116-OX and SW620-OX). Compared with parental cell lines, $IC_{50}$s for various chemotherapeutic agents (oxaliplatin, cisplatin and doxorubicin) were increased in oxaliplatin-resistant cell lines and this was accompanied by activation of nuclear factor erythroid-2 p45-related factor 2 (Nrf2) and NADPH quinone oxidoreductase 1 (NQO1). Furthermore, luteolin inhibited the Nrf2 pathway in oxaliplatin-resistant cell lines in a dose-dependent manner. Luteolin also inhibited Nrf2 target gene [NQO1, heme oxygenase-1 (HO-1) and $GST{\alpha}1/2$] expression and decreased reduced glutathione in wild type mouse small intestinal cells. There was no apparent effect in Nrf2-/- mice. Luteolin combined with other chemotherapeutics had greater anti-cancer activity in resistant cell lines (combined index values below 1), indicating a synergistic effect. Therefore, adaptive activation of Nrf2 may contribute to the development of acquired drug-resistance and luteolin could restore sensitivity of oxaliplatin-resistant cell lines to chemotherapeutic drugs. Inhibition of the Nrf2 pathway may be the mechanism for this restored therapeutic response.

• 대한수의학회지
• /
• 제20권2호
• /
• pp.113-118
• /
• 1980

Total of 11 strains of Ldctobacillus isolated from lactobacillus-fermented milk and-beverage in March 1980 were examined for susceptibility to 8 drugs, and transferability and transfer frequency of R plasmids by conjugation. Of 11 isolates each 2 strains were classified as L. cellobiosus and L. helveticus, each 1 strain as L. plantarum, L. lactis, L. acidophilus, L. delbrueckii, L. casei subsp. casei, L. casei subsp, tolerans and L. salivarius subsp, salivarius by Bergey's manual. Resistance was the most active to na lidixic acid(NA), followed in decreasing order by chloramphenicol(CP), ampicillin(AP), kanamycin(KM) and streptomycin(SM). All of isolates were resistant to NA, each 10 strains to CP and AP, 7strains to KM and 6 strains to SM, indicating all of the isolates were resistant to two or more drugs in combination. No strain was resistant to erythromycin(EM), penicillin(PC) and tetracycline(TC). The most frequently encountered resistant patterns were CP NA AP SM KM, followed by CP NA AP KM, NA AP, CP NA, CP NA AP and CP NA AP SM in order. Transfer experiment of drug resistance showed that of 11 resistant strains, 9 strains transferred parts of their resistance to AP or AP CP or SM AP, indicating 9 strains carried R plasmids determining R(AP), R(AP CP) and R(SM AP). The conjugal frequency of R(AP) from Lactobacillus to E. coli ranged from 2.5{\times}10^{-1} to $5.6{\times}10^{-4}%$, that of R(CP) ranged from 5.0{\times}10^{-1} to 5.0{\times}10^{-3}% and that of R(SM) ranged from 6.0{\times}10^{-5} to 1.4{\times}10^{-5}%, at $37^{\circ}C$ for 18 hours of incubation.

• Experimental and Molecular Medicine
• /
• 제50권11호
• /
• pp.12.1-12.12
• /
• 2018

Drugs targeting the epidermal growth factor receptor (EGFR), such as cetuximab and panitumumab, have been prescribed for metastatic colorectal cancer (CRC), but patients harboring KRAS mutations are insensitive to them and do not have an alternative drug to overcome the problem. The levels of ${\beta}$-catenin, EGFR, and RAS, especially mutant KRAS, are increased in CRC patient tissues due to mutations of adenomatous polyposis coli (APC), which occur in 90% of human CRCs. The increases in these proteins by APC loss synergistically promote tumorigenesis. Therefore, we tested KYA1797K, a recently identified small molecule that degrades both ${\beta}$-catenin and Ras via $GSK3{\beta}$ activation, and its capability to suppress the cetuximab resistance of KRAS-mutated CRC cells. KYA1797K suppressed the growth of tumor xenografts induced by CRC cells as well as tumor organoids derived from CRC patients having both APC and KRAS mutations. Lowering the levels of both ${\beta}$-catenin and RAS as well as EGFR via targeting the $Wnt/{\beta}$-catenin pathway is a therapeutic strategy for controlling CRC and other types of cancer with aberrantly activated the $Wnt/{\beta}$-catenin and EGFR-RAS pathways, including those with resistance to EGFR-targeting drugs attributed to KRAS mutations.

• Journal of Veterinary Science
• /
• 제22권3호
• /
• pp.25.1-25.16
• /
• 2021

Background: Malignant lymphoma is the most common hematopoietic malignancy in dogs, and relapse is frequently seen despite aggressive initial treatment. In order for the treatment of these recurrent lymphomas in dogs to be effective, it is important to choose a personalized and sensitive anticancer agent. To provide a reliable tool for drug development and for personalized cancer therapy, it is critical to maintain key characteristics of the original tumor. Objectives: In this study, we established a model of hybrid tumor/stromal spheroids and investigated the association between canine lymphoma cell line (GL-1) and canine lymph node (LN)-derived stromal cells (SCs). Methods: A hybrid spheroid model consisting of GL-1 cells and LN-derived SC was created using ultra low attachment plate. The relationship between SCs and tumor cells (TCs) was investigated using a coculture system. Results: TCs cocultured with SCs were found to have significantly upregulated multidrug resistance genes, such as P-qp, MRP1, and BCRP, compared with TC monocultures. Additionally, it was revealed that coculture with SCs reduced doxorubicin-induced apoptosis and G2/M cell cycle arrest of GL-1 cells. Conclusions: SCs upregulated multidrug resistance genes in TCs and influenced apoptosis and the cell cycle of TCs in the presence of anticancer drugs. This study revealed that understanding the interaction between the tumor microenvironment and TCs is essential in designing experimental approaches to personalized medicine and to predict the effect of drugs.