Drug repositioning is a strategy for identifying new antitumor drugs; this strategy allows existing and approved clinical drugs to be innovatively repurposed to treat tumors. Based on the similarities between parasitic diseases and cancer, recent studies aimed to investigate the efficacy of existing antiparasitic drugs in cancer. In this review, we selected two antihelminthic drugs (macrolides and benzimidazoles) and two antiprotozoal drugs (artemisinin and its derivatives, and quinolines) and summarized the research progresses made to date on the role of these drugs in cancer. Overall, these drugs regulate tumor growth via multiple targets, pathways, and modes of action. These antiparasitic drugs are good candidates for comprehensive, in-depth analyses of tumor occurrence and development. In-depth studies may improve the current tumor diagnoses and treatment regimens. However, for clinical application, current investigations are still insufficient, warranting more comprehensive analyses.
PurposeGastric cancer, the cancer initiated from the stomach, is ranked as the third most frequent reason of cancer death worldwide. Gastric cancer-initiating cells (CICs) are one of the crucial causes for the metastasis and recurrence of gastric cancer, and CD44 is considered to be one marker for gastric CICs. Special AT-rich sequence binding protein 1 (SATB1) is a protein that promotes cancer progression, metastasis, and invasion and also participates in the maintenance of CICs. In this study, we investigated the therapeutic effect of SATB1 siRNA against gastric CICs and we constructed SATB1 siRNA-encapsulated immunoliposomes conjugated with CD44 antibodies (CD44-SATB1-ILs) to enhance the therapeutic effect of SATB1 siRNA against gastric CICs.MethodsWe investigated the therapeutic effect of the SATB1 suppression by SATB1 siRNA on CD44+ gastric CICs. CD44-SATB1-ILs were developed by the lyophilization/hydration approach. The targeting and cytotoxic effect of CD44-SATB1-ILs toward gastric CICs were evaluated in vitro.ResultsIn this study, for the first time, we confirmed that SATB1 suppression by SATB1 siRNA preferentially eliminated CD44+ gastric CICs. The results showed that CD44-SATB1-ILs could efficiently and specifically promote the SATB1 siRNA delivery to CD44+ gastric CICs, achieving superior therapeutic effects against CD44+ gastric CICs than non-targeted liposomes.ConclusionAs far as we know, our report is the first research that indicated the promotion of siRNA delivery via nanoparticles to gastric CICs and achievement of superior therapeutic effect against gastric CICs by utilization of CD44 antibody. Therefore, CD44-SATB1-ILs represent an up-and-coming approach for eliminating gastric CICs and also a promising treatment for therapy of gastric cancer.
Aim: USP22, a member of ubiquitin-specific proteases (USPs), is a well-defined protein that promotes poor prognosis, invasion and metastasis, and also participates in the maintenance of cancer stem cells. USP22 siRNA-loaded nanoliposomes conjugated with CD44 antibodies (USP22-NLs-CD44) were constructed to enhance the therapeutic effect of USP22 siRNA against gastric cancer stem cells. Materials & methods: The targeting and therapeutic efficacies of USP22-NLs-CD44 against gastric cancer stem cells were evaluated. Results & conclusion: USP22-NLs-CD44 was demonstrated to be able to effectively deliver USP22 siRNA to CD44+ gastric cancer stem cells, achieving superior therapeutic effects against CD44+ gastric cancer stem cells than nontargeted nanoliposomes. USP22-NLs-CD44 may provide a novel approach to eradicate gastric cancer stem cells in the near future.
Benzo[a]pyrene (BaP) is a known carcinogen. Grilled or smoked meat is the major source of BaP intake for human beings. Previously, we established hepatic tumor animal models by injecting rat hepatoma N1-S1 cells or concomitant injection of N1-S1 cells and BaP into healthy Sprague-Dawley rats. In this study, we performed proteomic analyses of rat plasma collected from a hepatic tumor model and compared them to controls using a 3-10 pI range and large two dimensional gel electrophoreses. Proteomic analyses of rat plasma with hepatic tumors induced by the injection of N1-S1 cells resolved 1295 protein spots. Among them, 10 proteins were identified by ESI-MS-MS; four proteins were up-regulated and six proteins were down-regulated as compared to the controls. In addition, 1295 protein spots were also resolved from rats with hepatic tumors by the injection of N1-S1 cells plus BaP; five proteins were upregulated, and seven proteins were down-regulated. Of these 12 proteins, 10 proteins were identified by ESI-MS-MS. Out of 20 identified proteins, alpha-1-inhibitor 3 and zero beta-1 globin were down-regulated in both rats with hepatic tumors by N1-S1 cell-only and rats with hepatic tumors by the injection of N1-S1 cell plus BaP as compared to the controls. In addition, the identities of four proteins, including dermcidin, serum amyloid P-component (SAP), proteasome subunit alpha type-4 and glutathione peroxidase 3 (GPX-3) were confirmed by western blot analysis. Therefore, the importance of those proteins as candidate biomarkers for the development of hepatic tumors should be further elucidated.
Positron emission tomography (PET) is a sensitive non-invasive imaging technique. To reduce imaging measurements of defects, there is a demand for proper LC-ESI-MS/MS method to carry out with its specificity and sensitivity. This study describes a rapid and simple liquid chromatography electrospray ionization tandem-MS/MS (LC-ESI-MS/MS) method for determination of both PET tracers: N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridyl)cyclohexanecarboxamide (WAY-100635) and 4-fluoro-N-[2-[4-(2-methoxylphenyl)-1-piperazino]ethyl]-N-(2-pyridyl)cyclohexanecarboxamide (FCWAY). Both target compounds were prepared by one-step protein precipitation with acetonitrile and methanol (1:1, v/v), and analyzed using a C18 column. This simple method has an excellent linearity, selectivity and sensitivity. Precision and accuracy values for the intra-day and inter-day validation were below 12%. The limit of quantification (LOQ) for both target compounds was defined as 1 ng/mL in plasma and 5 ng/mL in brain homogenate. The stability of both compounds is considered stable under a various experimental conditions. The in vitro MDR-MDCK cell permeability showed the both compounds have high permeability (Papp, A→B ≥ 20 × 10(-6 )cm/s) and low efflux ratio (≤2.0). Brain to blood (AUCbrain/AUCblood) distribution ratios in rats were 3.15 ± 0.42 for WAY-100635 and 2.20 ± 0.34 for FCWAY, respectively, and these results suggest that LC-ESI-MS/MS method might be a supplementary way for the identifying and understanding of radiopharmaceuticals.
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