Carbohydrates, one of the most important compounds in living organisms, perform numerous roles, including those associated with the extracellular matrix, energy-related compounds, and information. Of these, polymeric carbohydrates are a class of substance with a long history in drug delivery that have attracted more attention in recent years. Because polymeric carbohydrates have the advantages of nontoxicity, biocompatibility, and biodegradability, they can be used in drug targeting, sustained drug release, immune antigens and adjuvants. In this review, various carbohydrate-based or carbohydrate-modified drug delivery systems and their applications in disease therapy have been surveyed. Specifically, this review focuses on the fundamental understanding of carbohydrate-based drug delivery systems, strategies for application, and the evaluation of biological activity. Future perspectives, including opportunities and challenges in this field, are also discussed.
Ovarian clear cell carcinoma (OCCC) is a rare subtype of epithelial ovarian cancer with unique molecular characteristics, specific biological and clinical behavior, poor prognosis and high resistance to chemotherapy. Pushed by the development of genome-wide technologies, our knowledge about the molecular features of OCCC has been considerably advanced. Numerous studies are emerging as groundbreaking, and many of them are promising treatment strategies. In this article, we reviewed studies about the genomics and epigenetics of OCCC, including gene mutation, copy number variations, DNA methylation and histone modifications.
Ovarian cancer remains the most common gynecologic malignancy, because of its chemotherapy resistance and relapse. Anlotinib, a new oral multi-targeted tyrosine kinase inhibitor, has shown encouraging antitumor activity in several preclinical and clinical trials, while its effect on ovarian cancer has not been reported. In this study, we investigated the antitumor activity and underlying mechanism of anlotinib in ovarian cancer. Cell viability was analyzed by Cell Counting Kit-8 assay. Migration was measured by wound-healing assay. The cell cycle distribution and cell apoptosis rate were detected by flow cytometry. In vivo antitumor effect was analyzed in mouse ovarian carcinoma peritoneal metastasis model. We found that anlotinib inhibited the proliferation of ovarian cancer cells in a dose- and time- dependent manner by inducing G2/M phase arrest and apoptosis. Moreover, anlotinib upregulated the the phosphorylation of Histone H3, and expression of p21 protein in vitro. In addition, anlotinib inhibited the migration of ovarian cancer cells in vitro. Furthermore, anlotinib inhibited tumor growth by inhibiting cell proliferation and suppressing ovarian cancer angiogenesis in vivo. This study demonstrated the extraordinary anti-ovarian cancer effect of anlotinib, which may provide a promising therapeutic strategy for ovarian cancer.
1 March 2022 in European Journal of Pharmaceutical Sciences
SY-007 is an interfering peptide designed to disrupt the cell death signaling of phosphatase and tensin homolog deleted on chromosome ten (PTEN) nuclear translocation during ischemic stroke. Preclinical studies indicated that rats treated with 1.5 mg/kg SY-007 in the middle cerebral artery occlusion (MACO) model had significantly reduced stroke lesion size even when administered 6 h after the stroke onset. The aim of this study was to evaluate the safety, tolerability, and pharmacokinetics of ascending doses of SY-007 administered intravenously in healthy Chinese subjects. A total of 78 healthy Chinese subjects were enrolled in the single ascending dose study (1-60 mg) and received a 15-min intravenous infusion SY-007 or placebo. Plasma concentrations of SY-007 were measured by a validated liquid chromatography-tandem mass spectrometry method. Pharmacokinetic parameters were determined using non-compartmental and compartment analyses. A model based on target-mediated drug disposition was applied. Model evaluation was performed through visual predictive checks and bootstrap analysis. Across doses of 1-60 mg, SY-007 was well tolerated. All adverse events (AEs) were mild or moderate in intensity, and all resolved without intervention. After infusion, SY-007 plasma concentrations decreased quickly with the mean terminal half-life was shorter than 0.78 h. The area under the concentration-time curve increased with a greater than dose-dependent manner from 1 to 30 mg and resulted in a dose-dependent increased from 30 to 60 mg. The nonlinear phenomenon was well described by a simplified target-mediated drug disposition (TMDD) model. Intravenous dosing of SY-007 appears to be safe up to a dose of 60 mg. Nonlinear pharmacokinetics was observed across the evaluated doses and TMDD might be the primary reason. The effective dose of SY-007 for neuroprotective effect in patients with ischemic stroke is expected to be 10-30 mg and was recommended for the later multiple ascending dose study of SY-007. Clinicaltrials.gov: NCT04111523.