Cancer is one of the prominent causes of death worldwide. Despite the existence of various modalities for cancer treatment, many types of cancer remain uncured or develop resistance to therapeutic strategies. Furthermore, almost all chemotherapeutics cause a range of side effects because they affect normal cells in addition to malignant cells. Therefore, the development of novel therapeutic agents that are targeted specifically toward cancer cells is indispensable. Immunotoxins (ITs) are a class of tumor cell-targeted fusion proteins consisting of both a targeting moiety and a toxic moiety. The targeting moiety is usually an antibody/antibody fragment or a ligand of the immune system that can bind an antigen or receptor that is only expressed or overexpressed by cancer cells but not normal cells. The toxic moiety is usually a protein toxin (or derivative) of animal, plant, insect, or bacterial origin. To date, three ITs have gained Food and Drug Administration (FDA) approval for human use, including denileukin diftitox (FDA approval: 1999), tagraxofusp (FDA approval: 2018), and moxetumomab pasudotox (FDA approval: 2018). All of these ITs take advantage of bacterial protein toxins. The toxic moiety of the first two ITs is a truncated form of diphtheria toxin, and the third is a derivative of Pseudomonas exotoxin (PE). There is a growing list of ITs using PE, or its derivatives, being evaluated preclinically or clinically. Here, we will review these ITs to highlight the advances in PE-based anticancer strategies, as well as review the targeting moieties that are used to reduce the non-specific destruction of non-cancerous cells. Although we tried to be as comprehensive as possible, we have limited our review to those ITs that have proceeded to clinical trials and are still under active clinical evaluation.
Background. Staphylococcus aureus (S. aureus) is one of the most common pathogens that cause hospital- and community-acquired infections in the world. The use of molecular typing methods is essential for determining the origin of the strains, their clonal relations, and also in epidemiological investigations. The purpose of this study was to determine the prevalence of antibiotic resistant S. aureus isolates and using spa, agr, and SCCmec typing to determine the dominant types in Iran. Material and Method. Fifty isolates of S. aureus were collected from January to May 2010. S. aureus identification was performed by biochemical tests. Disk diffusion method was employed to assess the sensitivity of S. aureus strains to antibiotics and then genetic analysis of bacteria was performed using SCCmec, agr, and spa typing. Results. S. aureus resistance to tetracycline, cefoxitin, clindamycin, ciprofloxacin, gentamicin, Cot: cotrimoxazole, levofloxacin, rifampin, and vancomycin were found to be 36%, 18%, 12%, 12%, 22%, 6%, 6%, and 0%, respectively. The results of this study showed that 16% of the isolates were resistant to methicillin (MRSA) and the majority of isolates were SSC mec type IV. In addition spa and agr typing revealed agr typeI and spa type t7688 to be the most predominant. Conclusion. In this study, spa typing showed 100% reliability and the t7688 spa type had a frequency of 26% compared to the frequency of 0.0% in the Ridom SpaServer. The frequency of t304 spa type was higher than the global average.
Background: Staphylococcus aureus is one of the major causes of community-and hospital-acquired infections, with methicillinresistant strains showing the highest rates of morbidity and mortality. In our previous experiment, isolates, which were also used in the present study, were assessed using multilocus sequence typing (MLST). The sequence types (STs) were determined and documented in the corresponding database. Objectives: In the current study, the isolates were subjected to genotyping with coagulase, SCCmec, and agr typing methods. Methods: A total of 54 isolates were evaluated by polymerase chain reaction (PCR) assay for mecA gene, Sccmec typing, and finally PCR-restriction fragment length polymorphism (RFLP) for coagulase (coa) gene using Alul enzyme. MLST of the isolates showed that the majority of methicillin-resistant S. aureus (MRSA) isolates belonged to ST239. Results: Phenotypic and genotypic tests revealed that 21% of the isolates were MRSA. PCR-RFLP test for coa gene showed similar patterns of MRSA isolates. The majority of the isolates were community-acquired and belonged to the Sccmec type IV, whereas the remaining were hospital-acquired and classified as type I (22.2%) and type III (2.2%). Conclusions: Most of the isolates belonged to agr type I, followed by type II and type III. Agar dilution method showed higher sensitivity and specificity, compared to the disk diffusion method. The majority of the isolates were community-acquired and belonged to Sccmec type IV and agr type I, whereas the remaining were hospital-acquired and classified as types I (22.2%), type III (2.2%), and agr type I.
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