Objectives Heat-shock protein-90 (HSP90) chaperone machinery is critical to the folding, stability and activity of several client proteins including many responsible for tumour initiation, progression and metastasis. Overexpression of HSP90 is correlated with poor prognosis of GI cancer. Key findings Pharmacological inhibitors of HSP90 suppress tumorigenic effects of HSP90 by suppressing angiogenesis, survival, metastasis and drug resistance in GI cancer. This review summarizes the role of HSP90 inhibitors in the treatment of GI cancer. Summary We have presented different antitumour mechanisms of HSP90 inhibitors in cancer treatment. Suppression of HSP90 signalling via specific and novel pharmacological inhibitors is a potentially novel therapeutic approach for patients with GI cancer for a better understanding and hence a better management of this disease.
BackgroundMultidrug resistant strains of Acinetobacter baumannii (MDR-AB) have emerged as alarming nosocomial pathogens among patients admitted to Intensive Care Unit and burned patients. The aim of this study was to determine the susceptibility of A. baumannii isolates, the carbapenems resistance patterns bla OXA-23 and also ISAba elements of A. baumannii isolates among burned and ICU patients in Tehran and Sari, Iran.MethodsIn this study, 100 A. baumannii isolates from burned and ICU patients in Tehran and Sari (Iran) during 2013 were tested for determination of antimicrobials susceptibility by the disc-diffusion method on Mueller Hinton agar recommended by the guidelines of Clinical and Laboratory Standards Institute (CLSI), and frequency blaOXA-23 carbapenemase genes, and insertion elements ISAba genes were studied by PCR method.ResultsThe highest rates of susceptibility were observed with Colistin (88.7%), Tigecycline (82.2%), Imipenem (67%) and ISAba (32.2%). The extensively drug-resistance and pan drug-resistance were observed in 37.1% and 8.1% isolates, respectively.Results indicated among isolates resistant to Aminoglycoside and Carbapenem, the highest resistance was observed to Streptomycin (90%) ‚ and the most sensitivity was to Imipenem (67%).ConclusionsThis is the most study that attempted to detect Acinetobacter baumanii the insertion elements ISAba, bla OXA-23 and aminoglycosides resistance in MDR-AB isolates from burned and ICU patients in Iran. In a timely manner, antimicrobial resistance surveillance and strict infection control strategies are still lacking in burn ward and ICU in Iran, despite the alarming emergence of MDR-AB strains, particularly among those isolates that are not susceptible to Colistin. The results of this study are consistent with a recent report in which a number of combinations exhibited potent activity against Multidrug resistant strains of A. baumannii (MDR-AB).
Background: Infection due to Acinetobacter baumannii has become a significant challenge to modern healthcare systems. The rapid emergence and global dissemination of A. baumannii as a major nosocomial pathogen is remarkable and it demonstrates its successful adaptation to the 21st century hospital environment. Recent studies have discussed about essential oil of Origanum vulgare against a range of bacteria, including various species of Staphylococcus, Pseudomonas, Bacillus and Escherichia coli. Objectives: The present study aimed to investigate the inhibitory effects O. vulgare essence against multidrug-resistant (MDR) strains of A. baumannii from selected hospitals in Tehran, Iran. Materials and Methods: This oil was obtained using the hydrodistillation method and analyzed by gas chromatography mass spectrography (GC/MS). The antimicrobial activity against MDR isolates was achieved using disc diffusion method and macro-broth dilution assay. Results: Analysis of the essential oil revealed the presence of pulegone (68.59%) piperitone (7.8%), piperitenone (7.8%), 1, 8-cineole (1.3%), and carvacrol (1.6%) as the major components. The results showed a significant activity against MDR A. baumannii with inhibition zones and minimal inhibitory concentration values in the ranges of 7-15 mm and 20-35 µL/mL respectively. Conclusions: This investigation showed that the essence oil of O. vulgare had a potent antimicrobial activity against MDR A. baumannii. Further research is required to evaluate the practical values of therapeutic applications.
Background: Pseudomonas aeruginosa is an opportunistic pathogen that can cause severe hospital-acquired infections, especially in immunocompromised hosts. P.aeruginosa for its resistance to antibiotics. Efflux pump is one of the several mechanisms involved in intrinsic resistance of these bacteria to antibiotics. It has been revealed that deletion of genes encoding the components of MexAB-OprM of efflux system, in wildtype P. aeruginosa, confers hypersusceptibility to a variety of antimicrobial agents. Antimicrobial and antifungal properties of some herbal medicines were reported. Objectives: In this study the effect of Saturejakhuzestanica extract, an endemic plant of Iran, on the expression level of mexA, and mexR genes in P. aeruginosa were investigated. Materials and Methods: In this study, MIC was determined for P. aeruginosa. Then, bacteria were treated with S. khuzistanica extract. MexA, mexR and gyrA genes expression in treated and non-treated bacteria, before and after treatment was evaluated using RT-PCR technique. Results: Surprisingly, the expression level of mexA and mexR genes was decreased in the presence of S. Khuzestanica. However, the expression of gyrAgene that was used as an internal control was not altered before and after treatment with this herb. Based on the results, S. Khuzestanica could play a, major role in lowering the P. aeruginosa resistance to drugs, by reducing mexA genes expression. Conclusions: According to results of current research we hope in future be used it to the clinic with a wider range as a complementary therapy and also for surgery operation.
Background: Acinetobacter baumannii is one of the Gram-negative bacteria in nosocomial infections that is resistant to treatment and control. The isolation of these bacteria is increasing significantly throughout the world. With increasing populations and a reduction in the use of synthetic drugs, many of these medicinal herbs are replacing other treatments. Objectives: The present study aims to investigate the inhibitory effects of Satureja khuzestaniea essence on the expression of the antibiotic resistance genes bla-OXA-23 and Housekeeping DNA gyrase-A in multidrug-resistant strains of Acinetobacter baumannii, using
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