• Journal of Yeungnam Medical Science
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• 제36권2호
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• pp.67-77
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• 2019

The paradigm of chronic liver diseases has been shifting. Although hepatitis B and C viral infections are still the main causes of liver cirrhosis and hepatocellular carcinoma (HCC), the introduction of effective antiviral drugs may control or cure them in the near future. In contrast, the burden of nonalcoholic fatty liver disease (NAFLD) has been increasing for decades, and 25 to 30% of the general population in Korea is estimated to have NAFLD. Over 10% of NAFLD patients may have nonalcoholic steatohepatitis (NASH), a severe form of NAFLD. NASH can progress to cirrhosis and HCC. NASH is currently the second leading cause to be placed on the liver transplantation list in the United States. NAFLD is associated with obesity, type 2 diabetes, dyslipidemia, and metabolic syndrome. The pathophysiology is complex and associated with lipotoxicity, inflammatory cytokines, apoptosis, and insulin resistance. The only proven effective treatment is weight reduction by diet and exercise. However, this may not be effective for advanced fibrosis or cirrhosis. Therefore, effective drugs are urgently needed for treating these conditions. Unfortunately, no drugs have been approved for the treatment of NASH. Many pharmaceutical companies are trying to develop new drugs for the treatment of NASH. Some of them are in phase 2 or 3 clinical trials. Here, pharmacologic therapies in clinical trials, as well as the basic principles of drug therapy, will be reviewed, focusing on pathophysiology.

• 한국융합학회논문지
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• 제8권11호
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• pp.141-149
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• 2017

본 연구는 천안소재 천호저수지의 위생미생물학적 수준과 자연환경에서의 항생제 내성 분포를 파악하여 국민보건 향상에 이바지 하고자 하였다. 2013년 7월과 9월 3차에 걸쳐 위생지표세균인 대장균군수를 측정하고 수질오염공정시험기준에 따라 분리 동정하였으며 국립보건원 항생제 감수성 표준시험법을 사용하여 항생제 내성 시험을 하였다. 천호저수지의 평균 대장균군수는 $2.0{\times}10^3CFU/mL$이었으며 그 중 41%가 대장균으로 동정되었다. 대장균의 항생제 내성은 Ampicillin 31.3%로 가장 높았으며 Ticarcillin 25.0%, Cefazolin 및 Cefoxitin 이 18.8% 이었다. 융합다제내성은 4제내성이 38.5%, 6제 내성은 7.7%, 2제이상은 내성균의 92.3%를 차지하였다. 천호저수지는 시민들이 이용하는 공원으로 보건위생학적 수질관리를 위해 주기적인 위생미생물학적 연구와 항생제 내성에 관한 융합적인 관리가 필요하다.

• 대한미생물학회지
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• 제20권1호
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• pp.1-11
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• 1985

A total of 211 strains of Staphylococcus aureus which included 118 strains isolated from various clinical specimens of admitted patients of University Hospital with systemic or severe cases of infection and 93 strains from infected skin diseases of out-patients of dermatology clinic located in rural area, were tested for the antimicrobial susceptibility to the 12 drugs of common use and the phage typing. An these were subjected to the study of plasmid profile analysis for the molecular epidemiology of nosocomial infections. University Hospital(UH) isolates showed higher frequency of resistance than local clinic(LC) isolates against 10 drugs excluding tetracycline(Tc), and trimethoprim(Tp). The MIC of UH isolates were above than $128{\mu}g/ml$ against 9 drugs except Tc, gentamicin(Gm), and Tp, but LC isolates did not show such a high level of MIC. There was difference of MIC needed to inhibit 90% of strains(MIC90) against each drugs tested between two groups of UH and LC isolates. UH isolates showed 2 to 4 times higher value of MIC90 by two-fold serial dilution of drug concentration than LC isolates. Tp was considered as an effective drug in treatment of staphylococcal infections whereas ampicillin and Gm were appeared to be ineffective. Seventy-three strains(61.9%) of UH isolates and 70(69.9%) of LC were typable with phages from Colindale Reference Laboratory. The prevailing phage type of UH isolates belonged to lytic group II were 27 strains(22.9%) and those of LC isolates belonged to lytic group II were 23 strains(24.7%). Thirteen strains(11.0%) of UH isolates were multiply resistant to more than 5 drugs to 10 drugs but none of LC isolates. Through the lysis method of Kado and Liu followed by agarose gel electrophoresis, none of 211 strains showed plasmid profile. These results were confirmed by re-examination through the method of Birnboim and Doly.

• Asian Pacific Journal of Cancer Prevention
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• 제14권8호
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• pp.4853-4858
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• 2013

Objectives: To investigate whether hypoxia has an effect on regulation of multidrug resistance (MDR) to chemotherapeutic drugs in laryngeal carcinoma cells and explore the role of hypoxia-inducible factor-$1{\alpha}$ (HIF-$1{\alpha}$). Methods: Laryngeal cancer cells were cultured under normoxic and hypoxic conditions. The sensitivity of the cells to multiple drugs and levels of apoptosis induced by paclitaxel were determined by MTT assay and annexin-V/propidium iodide staining analysis, respectively. HIF-$1{\alpha}$ expression was blocked by RNA interference. The expression of HIF-$1{\alpha}$ gene was detected by real-time quantitative RT-PCR and Western blotting. The value of fluorescence intensity of intracellular adriamycin accumulation and retention in cells was evaluated by flow cytometry. Results: The sensitivity to multiple chemotherapy agents and induction of apoptosis by paclitaxel could be reduced by hypoxia (P<0.05). A the same time, the adriamycin releasing index of cells was increased (P<0.05). However, resistance acquisition subject to hypoxia in vitro was suppressed by down-regulating HIF-$1{\alpha}$ expression. Conclusion: HIF-$1{\alpha}$ could be considered as a key regulator for mediating hypoxia-induced MDR in laryngeal cancer cells via inhibition of drug-induced apoptosis and decrease in intracellular drug accumulation.

• 약학회지
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• 제49권1호
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• pp.38-43
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• 2005

The occurrence of resistance to chemotherapeutic drugs is a major problem for successful cancer treatment. This resistant phenotype of cancer cell frequently reveals a broad spectrum to structurally and/or functionally unrelated anticancer drugs, termed multidrug resistance (MDR). Overexpression of P-glycoprotein (P-gp), a transmembrane drug efflux pump, is a major mechanism of MDR. Accordingly, considerable effort has been directed towards to development of compounds that inhibit P-gp, reverse the MDR phenotype and sensitize cancer cells to conventional chemotherapy without undesired toxicological effects. In an effort to search for novel MDR reversal agent, we tested the cytotoxicity of paclitaxel, a well-known substrate of P-gp, against P-gp-expressing HCT15 and HCT15/CL02 human colorectal cancer cells in the presence or absence of benzotriazepin analogues, as well as against P-gp-negative A549 human non-small cell lung and SK-OV-3 human ovarian cancer cells in vitro. Among the compounds tested, the agents that have phenyl amide moiety at 3 position remarkably increased the cytotoxicity of paclitaxel against P-gp-expressing cancer cells, but not against P-gp-negative cancer cells. BTZ-15 and BTZ-16 at $4\;{\mu}M$ revealed similar MDR reversal activity to $10\;{\mu}M$ verapamil, a well-known MDR reversal agent.

• Biotechnology and Bioprocess Engineering:BBE
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• 제6권4호
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• pp.252-263
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• 2001

Nematode infections compromise human health and reduce agricultural productivtiy. Experiments that exploit the powerful molecular genetics of the free-living nematode Caenorhabdl - elegans have contributed to our understanding of how the major classes of anthelmintic nema-tocides kill worms and how worms might evolve resistance to these drugs In C. elegans, as in parasites, benzimidixoles interfere with microtubule polyumerization the imidazothiazoles/tetra-hydropyrimidines activate nicotinic acetylcholine receptors, and the macrocyclic la ctones activate qlutamate-gate chloride chanels. Mutant alleles of genes that encode drug targes often confer resistance in C. elegans. Preliminary evidence suggests that alleles of homologous genes in parasites will, in many cases, also play a role in resistance. Thus information acquired from C. elegans can be usefully applied to understand the mechanisms of drug sensitivity and the genetics of resis-tance in parasites.

• 대한의생명과학회지
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• 제10권4호
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• pp.501-506
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• 2004

Extended spectrum β-lactamase (ESBL) generated Enterobacteriaceae including Escherichia coli is responsible for resisting antibiotics, which is clinical problem. This study was performed to investigate the isolation rates of 111 strains having positive of VITEK ESBL test 111 ESBL-strains in each month and season and statistically to determine their patterns of antibiotic test. One hundred eleven ESBL-strains were collected among 1,688 strains of E. coli isolated from various clinical specimen of one general hospital in Busan during 2002 to 2003. Month rates of ESBL-strains were 0％ to 13.3％, while the seasonal rates were highest at autumns during two years. The resistance to ampicillin, cefazolin, azteronam, ceftriaxone, and cefepime were 100％ in 2002. In ampicillin and cefazolin the resistances were 100％ during the two years. There were significant differences of cefoxitin and piperacillin/tazobactam between the two years but not significant between specimens. Four groups were divided according to the pattern of resistance and then the highest group had 93∼100％ of the resistance to 8 drugs but not resistant to imipenem.

• Journal of Pharmaceutical Investigation
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• 제37권5호
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• pp.287-290
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• 2007

Intrinsic or acquired resistance to chemotherapeutic drugs is one of the major obstacles to effective cancer treatment. Hypoxia is widespread in solid tumors as a consequence of decreased blood flow in the tumor-derived neovasculature. The recent finding of a link between hypoxia and chemoresistance prompted us to investigate whether hypoxia induces doxorubicin resistance in human MCF-7 breast cancer cells. Low oxygen concentration decreased the doxorubicin sensitivity in MCF-7 cells. The expression of p-glycoprotein, a major MDR-related transporter, and those of apoptosis-related proteins (anti-apoptotic Bcl-2, Bcl-XL and pro-apoptotic Bax) were not altered by hypoxia in MCF-7 cells. Intracellular uptake of doxorubicin was significantly decreased under hypoxic conditions. Decreased cellular uptake of doxorubicin under hypoxia may contribute to causing doxorubicin resistance in these cells. The use of agents that can modulate the doxorubicin uptake for adjuvant therapy may contribute to improving the therapeutic efficacy of doxorubicin in breast cancer patients.

• 한국식품영양과학회지
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• 제22권6호
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• pp.839-845
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• 1993

One of the major problems of cancer chemotheraphy is the development of drug resistance in tumors, resulting in reduced responsiveness to subsequent treatments. The folate antagonists are being used to treat such diverse illnesses as cancer, leukemia, psoriasis, rheumatoid arthritis, etc. Previous studies have established that resistance to antifolates may occur in mammalian tumor cells by one or more of five mechanisms ; (a) an increase in the levels of the target enzyme, generally as a consequence of gene amplification ; (b) an alteration in the target enzyme, leading to an enzyme with a decreased binding affinity for the drug ; (c) a decrease in the uptake of the drug into the cells ; (d) increased extrusion of drugs out of cells ; (e) impaired ability to polyglutamylate the parent drug which is capable of being intracellularly metabolized to longer chain length.

• Archives of Pharmacal Research
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• 제19권5호
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• pp.342-347
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• 1996

Doxorubicin, one of the clinically most useful anticancer agents, is used alone or in combination with other drugs against a wide variety of tumors, recently. But cancer cells developed resistance to this agent in many ways. This resistance is an important limiting factor of doxorubicin for anticancer drug. We newly established doxorubicin-resistant HCT15/CL02 subline from parental HCT15 human adenocarcinoma colon cancer cells. HCT15/CL02 revealed resistance to doxorubicin about 85-fold of its parental cells, and it also revealed cross-resistance to actinomycin D, etoposide and vinblastine but not to displatin and tamoxifen. And verapamil, a reversal agent of multidrug-resistance (MDR) by P-glycoprotein, elevated the cytotoxicity of doxorubicin against both HCT15 and GCT15/CL02 cells. But the relative resistant rate was not reduced. Verapamil had no effects on the tosicity of cisplatin to the both cell lines. These results indicate that HCT15/CL02 cells have some functionally complex mechanisms for MDR.