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Cancer stem cells (CSCs) are a subpopulation of cancer cells with functions similar to those of normal stem cells. Although few in number, they are capable of self-renewal, unlimited proliferation, and multi-directional differentiation potential. In addition, CSCs have the ability to escape immune surveillance. Thus, they play an important role in the occurrence and development of tumors, and they are closely related to tumor invasion, metastasis, drug resistance, and recurrence after treatment. Therefore, specific targeting of CSCs may improve the efficiency of cancer therapy. A series of corresponding promising therapeutic strategies based on CSC targeting, such as the targeting of CSC niche, CSC signaling pathways, and CSC mitochondria, are currently under development. Given the rapid progression in this field and nanotechnology, drug delivery systems (DDSs) for CSC targeting are increasingly being developed. In this review, we summarize the advances in CSC-targeted DDSs. Furthermore, we highlight the latest developmental trends through the main line of CSC occurrence and development process; some considerations about the rationale, advantages, and limitations of different DDSs for CSC-targeted therapies were discussed.
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Aims@#The aim of the study was to isolate and characterise bacteriophages specific to Pseudomonas aeruginosa carrying virulence genes. @*Methodology and results@#Four clinical strains of P. aeruginosa CL1, CL2, CL3 and CL4 were obtained from Queen Elizabeth Hospital, Kota Kinabalu, Sabah. The bacterial strains were screened for virulence genes exoS, toxA and oprI and biofilm production. Six P. aeruginosa specific bacteriophages, namely PAtk1, PAtk2, PAtk3, PAtk4, PAtk5 and PAtk6, were isolated from Tasik Kejuruteraan, Universiti Kebangsaan Malaysia. These bacteriophages were screened for lytic spectrum against P. aeruginosa and two species of Enterobacteriaceae (Escherechia coli and Salmonella Typhi). PCR results showed that all strains possessed exoS, toxA and oprI genes except CL2 that lacked exoS. Nevertheless, it was CL2 that produced the highest biofilm density. Further, based on Transmission Electron Microscopy, PAtk15 and PAtk6 were classified into the family Myoviridae and Siphoviridae, respectively. Among all six isolated phages, only PAtk4 and PAtk6 showed the broadest lytic spectrum in which lytic activity was observed against all clinical P. aeruginosa strains. @*Conclusion, significance and impact of study@#In this study we reported the isolation of six bacteriophages from Myoviridae and Siphoviridae that are specific to P. aeruginosa possessing exoS, toxA and oprI genes. Bacteriophages Patk4 and PAtk6 were able to infect all four strains of P. aeruginosa, making these phages potential agents in combating infections by the bacterium.
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We investigated the correlation between toxin gene exoS,exoU and fluoroquinolone resistance in lower respiratory tract infection with P.aeruginosa so as to provide guidance for reasonable treatment of clinical infections.We collected P.aeruginosa of sputum samples in hospitalized patients from October 2015 to March 2016.The antimicrobial susceptibility was tested by liquid dilution method.The exoS and exoU genes were detected by PCR technique.Results showed that forty-six P.aeruginosa strains were identified from sputum.The exoS and exoU gene positive rate were 86.96 ％ (40/46) and 69.57 ％ (32/ 46) respectively,and the highest proportion of genotype was exoS+/exoU+ (60.87％,28/46).Among them,36.96％ (17/ 46) were multiple drug-resistant bacteria(MDR).Fluoroquinolone non-sensitive (FQ-NS) strain were 78.95％ (15/19) for MDR and 89.47 ％ (17/19) exoU gene were positive,which was significantly higher than the fluoroquinolone sensitive strains (FQ-S).Compared with the FQ-S strain,FQ-NS strains were serious drug resistance.The drug resistant rate of eefepime and aztreonam were more than 70％,and then meropenem and imipenem were more than 50％.The drugs of lower resistance rate in FQ-NS strain had polymyxin B(10.53％,2/19),amikacin(10.53％,2/19),ceftazidime (15.79％,3/19) and gentamicin (21.05％,4/19).P.aeruginosa of lower respiratory infection carried toxin genes exoS and exoU were higher,the main genetpy was exoS+/exoU+.FQ-NS strains were higher drug resistance rate and a higher proportion of exoU+ strains than FQ-S strains.We should strengthen virulence genes test and drug resistance monitoring in clinical practice.
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BACKGROUND: Pseudomonas aeruginosa is a clinically important pathogen that causes opportunistic infections and nosocomial outbreaks. Recently, the type III secretion system (TTSS) has been shown to play an important role in the virulence of P. aeruginosa. ExoU, in particular, has the greatest impact on disease severity. We examined the relationship among the TTSS effector genotype (exoS and exoU), fluoroquinolone resistance, and target site mutations in 66 carbapenem-resistant P. aeruginosa strains. METHODS: Sixty-six carbapenem-resistant P. aeruginosa strains were collected from patients in a university hospital in Daejeon, Korea, from January 2008 to May 2012. Minimum inhibitory concentrations (MICs) of fluoroquinolones (ciprofloxacin and levofloxacin) were determined by using the agar dilution method. We used PCR and sequencing to determine the TTSS effector genotype and quinolone resistance-determining regions (QRDRs) of the respective target genes gyrA, gyrB, parC, and parE. RESULTS: A higher proportion of exoU+ strains were fluoroquinolone-resistant than exoS+ strains (93.2%, 41/44 vs. 45.0%, 9/20; P< or =0.0001). Additionally, exoU+ strains were more likely to carry combined mutations than exoS+ strains (97.6%, 40/41 vs. 70%, 7/10; P=0.021), and MIC increased as the number of active mutations increased. CONCLUSIONS: The recent overuse of fluoroquinolone has led to both increased resistance and enhanced virulence of carbapenem-resistant P. aeruginosa. These data indicate a specific relationship among exoU genotype, fluoroquinolone resistance, and resistance-conferring mutations.