ABSTRACT
The extremely low bioavailability of oral paclitaxel (PTX) mainly due to the complicated gastrointestinal environment, the obstruction of intestinal mucus layer and epithelium barrier. Thus, it is of great significance to construct a coordinative delivery system which can overcome multiple intestinal physicochemical obstacles simultaneously. In this work, a high-density PEGylation-based glycocholic acid-decorated micelles (PTX@GNPs) was constructed by a novel polymer, 9-Fluorenylmethoxycarbonyl-polyethylene glycocholic acid (Fmoc-PEG-GCA). The Fmoc motif in this polymer could encapsulate PTX via π‒π stacking to form the core of micelles, and the low molecular weight and non-long hydrophobic chain of Fmoc ensures the high-density of PEG. Based on this versatile and flexible carriers, PTX@GNPs possess mucus trapping escape ability due to the flexible PEG, and excellent intestine epithelium targeting attributed to the high affinity of GCA with apical sodium-dependent bile acid transporter. The in vitro and in vivo results showed that this oral micelle could enhance oral bioavailability of PTX, and exhibited similar antitumor efficacy to Taxol injection via intravenous route. In addition, oral PTX@GNPs administered with lower dosage within shorter interval could increase in vivo retention time of PTX, which supposed to remodel immune microenvironment and enhance oral chemotherapy efficacy by synergistic effect.
ABSTRACT
Cancer stem cells (CSCs) are a subpopulation of cancer cells with functions similar to those of normal stem cells. Although few in number, they are capable of self-renewal, unlimited proliferation, and multi-directional differentiation potential. In addition, CSCs have the ability to escape immune surveillance. Thus, they play an important role in the occurrence and development of tumors, and they are closely related to tumor invasion, metastasis, drug resistance, and recurrence after treatment. Therefore, specific targeting of CSCs may improve the efficiency of cancer therapy. A series of corresponding promising therapeutic strategies based on CSC targeting, such as the targeting of CSC niche, CSC signaling pathways, and CSC mitochondria, are currently under development. Given the rapid progression in this field and nanotechnology, drug delivery systems (DDSs) for CSC targeting are increasingly being developed. In this review, we summarize the advances in CSC-targeted DDSs. Furthermore, we highlight the latest developmental trends through the main line of CSC occurrence and development process; some considerations about the rationale, advantages, and limitations of different DDSs for CSC-targeted therapies were discussed.
ABSTRACT
Objective To investigate the correlation between the expression of adhesion molecule CD146 and the vulnerability of carotid atherosclerotic plaque.Methods The plaque samples were collected from 40 patients who underwent the carotid endarterectomy and were divided into the stable plaque group and the instable plaque group by ultrasound imaging.Five carotid artery samples were taken from the healthy donors as the control.Immunohistochemistry was applied to test the CD146 expression in all samples.Results Higher expression of CD146 was observed in the atherosclerotic plaques than in the healthy control.Moreover,statistical difference was found in the expression of CD146 in the plaques between the instable plaque group and the stable plaque group (0.31 ± 0.19 vs 0.17 ± 0.07,P ＜ 0.05).The expression of CD146 was positively correlated with the necrotic area (r =0.471 8,P =0.019 9) and the matrix metalloproteinase (MMP)-9 expression in the plaques (r =0.535 6,P =0.000 9).Conclusion The CD146 expression is correlated with the vulnerability of carotid atherosclerotic plaque.
ABSTRACT
CD146 is a newly identified endothelial biomarker that has been implicated in angiogenesis. Though in vitro angiogenic function of CD146 has been extensively reported, in vivo evidence is still lacking. To address this issue, we generated endothelial-specific CD146 knockout (CD146(EC-KO)) mice using the Tg(Tek-cre) system. Surprisingly, these mice did not exhibit any apparent morphological defects in the development of normal retinal vasculature. To evaluate the role of CD146 in pathological angiogenesis, a xenograft tumor model was used. We found that both tumor volume and vascular density were significantly lower in CD146(EC-KO) mice when compared to WT littermates. Additionally, the ability for sprouting, migration and tube formation in response to VEGF treatment was impaired in endothelial cells (ECs) of CD146(EC-KO) mice. Mechanistic studies further confirmed that VEGF-induced VEGFR-2 phosphorylation and AKT/p38 MAPKs/NF-κB activation were inhibited in these CD146-null ECs, which might present the underlying cause for the observed inhibition of tumor angiogenesis in CD146(EC-KO) mice. These results suggest that CD146 plays a redundant role in physiological angiogenic processes, but becomes essential during pathological angiogenesis as observed in tumorigenesis.
Subject(s)
Animals , Female , Male , Mice , CD146 Antigen , Genetics , Metabolism , Cells, Cultured , Endothelial Cells , Cell Biology , Metabolism , Fibrosarcoma , Metabolism , Pathology , Melanoma, Experimental , Metabolism , Pathology , Mice, Inbred C57BL , Mice, Knockout , NF-kappa B , Metabolism , Neovascularization, Physiologic , Phosphorylation , Proto-Oncogene Proteins c-akt , Metabolism , Retinal Vein , Pathology , Signal Transduction , Transplantation, Homologous , Vascular Endothelial Growth Factor A , Pharmacology , Vascular Endothelial Growth Factor Receptor-2 , MetabolismABSTRACT
FXYD6, FXYD domain containing ion transport regulator 6, has been reported to affect the activity of Na(+)/K(+)-ATPase and be associated with mental diseases. Here, we demonstrate that FXYD6 is up-regulated in hepatocellular carcinoma (HCC) and enhances the migration and proliferation of HCC cells. Up-regulation of FXYD6 not only positively correlates with the increase of Na(+)/K(+)-ATPase but also coordinates with the activation of its downstream Src-ERK signaling pathway. More importantly, blocking FXYD6 by its functional antibody significantly inhibits the growth potential of the xenografted HCC tumors in mice, indicating that FXYD6 represents a potential therapeutic target toward HCC. Altogether, our results establish a critical role of FXYD6 in HCC progression and suggest that the therapy targeting FXYD6 can benefit the clinical treatment toward HCC patients.
Subject(s)
Animals , Female , Humans , Antibodies, Monoclonal , Pharmacology , Antineoplastic Agents , Pharmacology , Carcinoma, Hepatocellular , Drug Therapy , Metabolism , Cell Line, Tumor , Cell Movement , Cell Proliferation , HEK293 Cells , Ion Channels , Metabolism , Liver Neoplasms , Drug Therapy , Metabolism , Mice, Inbred BALB C , Mice, Nude , Sodium-Potassium-Exchanging ATPase , Metabolism , Tumor Burden , Xenograft Model Antitumor AssaysABSTRACT
Objective To explore the effect of therapeutic touch(massage)on the neuTobehavior of preterm infants.Methods Sixty preterm infants( gestafional age in 31-36 weeks),through natural delivery or caesarean section were randomly assigned to therapeutic touch group(n=30)and control group(n=30).Both groups re-ceived routine pharmacothempy and nursing care and followed up for half a year from discharge.Touch group re-ceived additional whole-body massage.All subjects were evaluated with neonatal behavioral neurological assessment (NBNA)in one month after birth-and mental development index(MDI), psyehomotor development index(PDI)in 3 months and 6 months after birth.Results The NBNA scores(P<0.01),as well as MDI and PDI(P<0.05)were significantly higher in therapeutic touch group than the control.Conclusion Therapeutic touch intervention im-proves nervous system of preterm infants.