ABSTRACT
Platinum-based chemotherapy resistance is a key factor of poor prognosis and recurrence in hepatocellular carcinoma (HCC). Herein, RNAseq analysis revealed that elevated tubulin folding cofactor E (TBCE) expression is associated with platinum-based chemotherapy resistance. High expression of TBCE contributes to worse prognoses and earlier recurrence among liver cancer patients. Mechanistically, TBCE silencing significantly affects cytoskeleton rearrangement, which in turn increases cisplatin-induced cycle arrest and apoptosis. To develop these findings into potential therapeutic drugs, endosomal pH-responsive nanoparticles (NPs) were developed to simultaneously encapsulate TBCE siRNA and cisplatin (DDP) to reverse this phenomena. NPs (siTBCE + DDP) concurrently silenced TBCE expression, increased cell sensitivity to platinum treatment, and subsequently resulted in superior anti-tumor effects both in vitro and in vivo in orthotopic and patient-derived xenograft (PDX) models. Taken together, NP-mediated delivery and the co-treatment of siTBCE + DDP proved to be effective in reversing chemotherapy resistance of DDP in multiple tumor models.
ABSTRACT
BACKGROUND: The combination of sorafenib and hepatic arterial infusion chemotherapy (HAIC) is expected to exert a synergistic anticancer effect. We conducted this systematic review to examine the efficacy and safety of sorafenib plus HAIC vs sorafenib alone for advanced hepatocellular carcinoma (HCC). METHODS: We systematically searched the PubMed, Embase, and Cochrane Library with the following search terms: "sorafenib," "hepatic arterial infusion chemotherapy," "HAIC," "advanced," "hepatocellular carcinoma," and "HCC." Pooled hazard ratios (HRs) and 95% CIs were calculated for overall survival (OS) and progression-free survival (PFS), and we calculated the pooled risk ratios (RRs) and 95% CIs for objective response rate (ORR) and adverse events (AEs). RESULTS: We found that sorafenib plus HAIC was associated with significantly better OS (HR, 0.56; 95% CI, 0.37-0.83; P < 0.01), PFS (HR, 0.44; 95% CI, 0.27-0.72; P < 0.01), and ORR (RR, 3.77; 95% CI, 1.87-7.58; P < 0.01) than sorafenib alone in advanced HCC. Grade 3/4 AEs were more frequent in the sorafenib plus HAIC group, including leukopenia (RR, 4.54; 95% CI, 1.77-11.64; P < 0.01), neutropenia (RR, 7.81; 95% CI, 3.36-18.16; P < 0.01), thrombocytopenia (RR, 2.97; 95% CI, 1.98-4.46; P < 0.01), anemia (RR, 2.24; 95% CI, 1.22-4.09; P < 0.01), anorexia (RR, 2.37; 95% CI, 1.07-5.27; P = 0.03), nausea (RR, 2.98; 95% CI, 1.19-7.42; P = 0.02), and vomiting (RR, 3.99; 95% CI, 1.14-14.01; P = 0.03). CONCLUSION: Sorafenib plus HAIC improved OS, PFS, and ORR compared with sorafenib alone in advanced HCC, with acceptable safety profile.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Thrombocytopenia , Humans , Sorafenib/therapeutic use , Liver Neoplasms/pathology , Treatment Outcome , Infusions, Intra-Arterial , Thrombocytopenia/etiology , Antineoplastic Combined Chemotherapy Protocols/adverse effectsABSTRACT
In this study we investigate the effects of cadmium stress on Astragalus membranaceus seedlings and the alleviative effects of attapulgite clay in growth substrate on cadmium stress to A. membranaceus seedlings. The results showed that the Y (Ⅱ) (effective photochemical quantum yield of PSⅡ photosynthetic), qP(photochemical quenching coefficient), ETR(the rate of non-cyclic electrontransport through PSⅡ), and chlorophyll content of the leaves were significantly decreased with the increase of cadmium concentrations, while the cadmium content, non-photochemical quenching(NPQ, qN) of the leaves and cadmium content, MDA content, plasma membrane permeability, and the damage degree of root apical membrane of the roots were significantly increased. Simultaneously, the activities of APX(ascorbate peroxidase), SOD(superoxide dismutase), POD(peroxidase), CAT(catalase), soluble protein content, and soluble sugar content of roots were increased first but then decreased with the increasing cadmium concentration. Under the condition of without Cd stress, the attapulgite clay into the growth substrate did not significantly affect above physiological indexes of leaves, but significantly increased SOD activity and soluble sugar content of roots and decreased the MDA content, damage degree of root apical membrane of roots, while other physiological indexes did not significantly change. Under cadmium stress, the presence of attapulgite clay in the growth substrate significantly alleviated the cadmium-induced decreases Y (Ⅱ), qP, ETR and chlorophyll content of leaves, and the CAT activity, soluble protein content, and soluble sugar content of roots. Under condition with cadmium stress, the presence of attapulgite clay significantly alleviated the cadmium-induced increases of leaves cadmium content, qN and NPQ, and the cadmium content, MDA content, plasma membrane permeability, damage degree of root apical membrane, SOD, POD, and APX activity of the roots. And, the alleviative effects of attapulgite clay on cadmium stress to A. membranaceus roots were more obvious with the increase of cadmium stress time. The above results showed that the addition of attapulgite clay into the growth substrate has certain alleviative effect on the cadmium stress to A. membranaceus seedlings.
ABSTRACT
OBJECTIVE:To establish an HPLC method for the determination of related substances in Donepezil hydrochloride tablets.METHODS:The separation was performed on AlltimaTM C18 column with mobile phase consisted of 0.01 mol?L-1 dipotassium hydrogen phosphate(3% triethylamine,pH=4.3)-methanol(60 :40) and flow rate of 1.0 mL?min-1.The detection wavelength was set at 271 nm and the column temperature was maintained at 35 ℃.The content of related substance was calculated by self-control with main component.RESULTS:Related substances were completely separated from the main constituent and the impurities were separated well from each other.The determination limit was 0.05 ng and the contents of related substances were 0.42%.CONCLUSION:The method is specific,sensitive and reproducible for the determination of related substances in Donepezil hydrochloride tablets.
