Methicillin-resistant Staphylococcus aureus (MRSA) produces specific penicillin-binding protein, PBP2', which shows remarkably low affinities to most beta-lactam antibiotics except those such as penicillin G and ampicillin. The region surrounding mecA has been called additional DNA or mec and is thought to be of extraspecies origin. From the study of mec, we found that mec is a novel mobile genetic element and designated as staphylococcal cassette chromosome mec (SCCmec). There are three types of SCCmec. In the past decades, MRSA has become resistant to many antibiotics, such as carbapenems, new quinolones, and minocycline etc. It seems to be a characteristic of MRSA to acquire multi-resistance by accumulating multiple resistance genes around the mecA gene inside SCCmec.
Drug Resistance, Microbial/physiology* ; Drug Resistance, Multiple/physiology* ; Methicillin Resistance/physiology* ; Staphylococcus aureus/physiology*

Pneumococcal resistance has become a global issue during the past three decades. One of the major foci of pneumococcal resistance worldwide is the Asian region including Korea, Japan, and Hong Kong. Korea had not been recognized as a focus of pneumococcal resistance until 1995, when serial reports documented the alarmingly high prevalence of penicillin resistance among clinical isolates. Serial reports on penicillin resistance among pneumococcal isolates in Korea ranged from 68% to 77% as of 1995. Multidrug resistance was also noted in 34% of Korean isolates. Penicillin-binding protein profile analysis, pulsed-field gel electrophoresis, ribotyping, and fingerprinting analysis of pbp genes showed that antibiotic-resistant pneumococci isolated in Korea were genetically related. Data documented the extensive spread of a resistant clone within Korea and between different countries. Besides the injudicious use of antimicrobial agents or the high prevalence of serotypes 23 and 19, the spread of a resistant clone may play an important role in the rapid increase of penicillin resistance in Korea.
Asia ; Drug Resistance, Microbial/physiology* ; Drug Resistance, Multiple/physiology ; Epidemiologic Methods ; Human ; Korea ; Streptococcus pneumoniae/physiology*

Necroptosis is a caspase-independent programmed cell death, its regulation, induction and blocking mechanism are a complex process involving in a series of molecular expression and regulation. The studies found that the necroptosis is not only involved in the physiological regulation mechanism, but also directly correlated to the occurrence, development and final outcome of some necrotic diseases, such as neurodegenerative diseases, ischemic disease, inflammation and viral infection. Moreover, the studies on multidrug-resistant tumor cell line demonstrated that necroptotic induction agents possess excellent "broad-spectrum" to escape the multidrug resistance. Therefore, exploration of the signaling pathways, physical characteristics, clinical relevance of necroptosis may provide new prospects for molecular target therapy and drug discovery of tumours. This review summarizes the research progress on possible regulation mechanism of necroptosis, physiologic characteristics and relation of necroptosis with clinical diseases and multi-drug resistance.
Apoptosis ; physiology ; Drug Resistance, Multiple ; Humans ; Necrosis ; Signal Transduction

Multidrug resistance (MDR) is a major impediment to the success of cancer chemotherapy. Multidrug resistance-associated proteins (MRPs) play an important role in the process of MDR. As an ATP-binding cassette (ABC) transporter superfamily, MRPs are selective and specific drug efflux pumps. In this paper, physiological characteristics, structural characteristics and resistance profile of MRPs and the associated reversal studies are reviewed.
Antineoplastic Agents ; pharmacology ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Humans ; Multidrug Resistance-Associated Proteins ; antagonists & inhibitors ; chemistry ; metabolism ; physiology ; Neoplasms ; drug therapy ; metabolism

OBJECTIVETo investigate the differential expression of RPL6/Taxreb107 between drug-resistant gastric cancer cell line SGC7901/ADR and gastric cancer cell line SGC7901 as well as its correlation with multiple-drug resistance (MDR) in gastric cancer cells.

METHODSTotal RNA was extracted from SGC7901 and SGC77901/ADR, with internal control RT-PCR, Northern blot, gene cloning and expression, construction of eukaryotic expression vector, gene transfection by electroporation. The accumulation and retention of ADR in transiently transfected cell was detected by flow cytometry.

RESULTSThe internal control RT-PCR and Northern blot showed high RPL6/Taxreb107 expression in SGC7901/ADR cell line. Sense and antisense eukaryonic expression vectors demonstrated by double enzyme digestion were successfully transfected into gastric cancer cell line SGC7901 and SGC7901/ADR respectively by electroporation. The accumulation and retention of ADR detected 48 hours after transfection showed that RPL6 gene had shown effect on drug resistance in gastric cancer cell.

CONCLUSIONThe high expression of RPL6/Taxreb107 in drug resistant gastric cancer cell shows its correlation with multiple-drug resistance in gastric cancer.

DNA-Binding Proteins ; metabolism ; Drug Resistance, Multiple ; physiology ; Drug Resistance, Neoplasm ; physiology ; Humans ; Statistics as Topic ; Stomach Neoplasms ; pathology ; Tumor Cells, Cultured

OBJECTIVETo analyze the distribution and significance of occludin mRNA expression in human gastric cancer, as well as its relationship with gastric cancer pathology and multidrug resistance (MDR) in vivo.

METHODSIn situ hybridization (ISH) technique was used to evaluate the expression of occludin mRNA in 42 gastric carcinoma specimens obtained by surgery and 23 relatively normal gastric mucosa obtained by gastric endoscopy. All specimens had been stored in cryostatic section.

RESULTSOccludin mRNA was found positive in the cytoplasm of gastric glandulous epithelia as blue particles with intensive stain in 14 of 42 gastric carcinomas (33.3%), 23 of 42 paracancerous gastric tissues (54.8%), 14 of 23 relatively normal gastric tissues (60.9%), 9 of 16 well differentiated carcinomas (56.3%), 4 of 14 moderately differentiated carcinomas (28.6%), 1 of 10 poorly differentiated carcinomas (10.0%) and none of 2 mucosal carcinomas. There were significant differences in occludin mRNA positive rate between relatively normal gastric tissue and gastric cancer as well as between paracancerous gastric tissue and gastric cancer. The expression of occludin mRNA in moderately and poorly differentiated groups was gradually reduced when compared with well differentiated group, which suggests that there be a significant correlation between tumor differentiation and the expression of occludin mRNA. Furthermore, the positive signals of occludin mRNA distributed extensively in the cytoplasm of SGC7901/VCR cell, being vincristine resistant, derived from parental gastric cell line SGC7901. The positive signals of SGC7901/VCR were stronger than those of SGC7901 cells.

CONCLUSIONOccludin mRNA, being mainly located in epithelial cells and its expression correlated with tumor differentiation, may be involved in the development of multi-drug resistance in gastric cancer.

Drug Resistance, Multiple ; physiology ; Drug Resistance, Neoplasm ; physiology ; Humans ; In Situ Hybridization ; Membrane Proteins ; genetics ; metabolism ; Occludin ; RNA, Messenger ; metabolism ; Stomach Neoplasms ; metabolism ; Tight Junctions ; metabolism

Although there are ever increasing reports of extraintestinal human infections caused by Aeromonads, in both immunocompromised and immunocompetent patients, respiratory tract infections remain uncommon. We describe a case of aspiration pneumonia in an immunocompetent patient with multiple sclerosis, caused by a community acquired, multidrug resistant strain of Aeromonas hydrophila sensitive only to meropenem. The case highlights the clinical significance of Aeromonas hydrophila as a respiratory pathogen, as well as the community origin of multidrug resistance and the utility of newer carbapenems in such cases.
Adolescent ; *Aeromonas hydrophila/physiology ; Drug Resistance, Microbial ; Drug Resistance, Multiple ; Female ; *Gram-Negative Bacterial Infections/drug therapy ; Human ; Pneumonia, Aspiration/*microbiology ; Thienamycins/therapeutic use

We analyzed the fluoroquinolone resistance mechanism of 28 isolates of ciprofloxacin-resistant E. coli from patients who received ciprofloxacin as a regimen of a selective gut decontamination. Isolates distinctive by infrequent restriction site polymerase chain reaction (IRS-PCR) were subjected to Hinf I restriction fragment length polymorphism analysis, single-stranded conformation polymorphism (SSCP), and nucleotide sequencing of the quinolone resistance determining region (QRDR) in gyrA. Double mutations in QRDR of gyrA (Ser83 Leu and Asp87Asn) were found from most of the strains. Nucleotide sequencing of the marR locus showed that 18 out of 28 (64%) ciprofloxacin-resistant E. coli strains had three types of base change in marR loci: a double-base change at nucleotides 1628 and 1751, or 1629 and 1751: and a single-base change at 1751. However, all the mutated strains showed no tolerance to cyclohexane test, suggesting the mutation in the marR region had no influence on overexpression of the MarA protein. In conclusion, mutation in gyrA was the main mechanism of ciporfloxacin resistance in E. coli from patients with selective gut decontamination. Therefore, mutation in the mar region did not influence the levels of ciprofloxacin resistance in our isolates.
Ciprofloxacin/pharmacology* ; DNA Topoisomerase (ATP-Hydrolysing)/genetics* ; Drug Resistance, Microbial/genetics* ; Drug Resistance, Multiple/genetics* ; Escherichia coli/genetics ; Escherichia coli/drug effects* ; Human ; Mutation/physiology

ATP-binding cassette (ABC) transporters are a family of proteins that mediate multi-drug resistance (MDR) via ATP-dependent drug efflux pumps. Abnormally expression and function would result in tumor MDR. That is the most important mechanism of MDR. The inhibition of ABC transporters as a strategy to reverse MDR in cancer has been studied extensively. In this review, we reviewed the structure and function of ABC transporters, and focused on the research advances in the mechanism of tumors MDR mediated by ABC transporters and the development of their modulators and reversal strategies.
ATP-Binding Cassette Transporters ; antagonists & inhibitors ; chemistry ; metabolism ; physiology ; Antineoplastic Agents ; therapeutic use ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Humans ; Neoplasms ; drug therapy ; physiopathology

OBJECTIVETo study the effect of human calcyclin binding protein (CacyBP) encoding gene on the development of multiple drug resistance in gastric cancer.

METHODShCacyBP sense nucleic acid eukaryotic expression vector (pcDNA3.1/hCacyBP +) was constructed and then transfected steadily into the gastric cancer drug sensitive cell (SGC7901) mediated by lipofectamine ( trade mark ) 2000. RT-PCR was used to measure the CacyBP mRNA expression level. MTT was used to measure the adriamycin (ADR) drug sensitivity of SGC7901 and SGC7901 after transfection. FCM was used to measure the average ADR accumulation concentration and cell cycle of SGC7901 and SGC7901 after transfection.

RESULTSThe hCacyBP mRNA expression level of SGC7901 transfected with pcDNA3.1/hCacyBP + was higher than SGC7901 transfected with pcDNA3.1 or SGC7901, with the higher survival rate in the former. The average ADR accumulation concentration in SGC7901 and SGC7901 transfected with pcDNA3.1 or pcDNA3.1/hCacyBP + was 5.64, 5.49 and 5.17, respectively. The G(1) phase cell proportion of SGC7901 transfected with pcDNA3.1/hCacyBP + or pcDNA3.1 was reduced slightly but G(2) and S phases increased slightly as compared with SGC7901.

CONCLUSIONCalcyclin binding protein may play a certain role in gastric cancer drug resistance.

Base Sequence ; Calcium-Binding Proteins ; genetics ; physiology ; DNA, Complementary ; analysis ; Drug Resistance, Multiple ; physiology ; Drug Resistance, Neoplasm ; physiology ; Drug Screening Assays, Antitumor ; Gene Transfer Techniques ; Humans ; Molecular Sequence Data ; Plant Lectins ; Stomach Neoplasms ; pathology ; Tumor Cells, Cultured