ABSTRACT
Brain metastasis is a common and serious complication of breast cancer, which is commonly associated with poor survival and prognosis. In particular, the treatment of brain metastasis from triple-negative breast cancer (BM-TNBC) has to face the distinct therapeutic challenges from tumor heterogeneity, circulating tumor cells (CTCs), blood-brain barrier (BBB) and blood-tumor barrier (BTB), which is in unmet clinical needs. Herein, combining with the advantages of synthetic and natural targeting moieties, we develop a "Y-shaped" peptide pVAP-decorated platelet-hybrid liposome drug delivery system to address the all-stage targeted drug delivery for the whole progression of BM-TNBC. Inherited from the activated platelet, the hybrid liposomes still retain the native affinity toward CTCs. Further, the peptide-mediated targeting to breast cancer cells and transport across BBB/BTB are demonstrated in vitro and in vivo. The resultant delivery platform significantly improves the drug accumulation both in orthotopic breast tumors and brain metastatic lesions, and eventually exhibits an outperformance in the inhibition of BM-TNBC compared with the free drug. Overall, this work provides a promising prospect for the comprehensive treatment of BM-TNBC, which could be generalized to other cell types or used in imaging platforms in the future.
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Objective To study the short-term variation patterns of graft viscosity after anterior cruciate ligament reconstruction (ACLR) surgery. Methods Six male New Zealand rabbits were selected. The ACLR animal model of unilateral knee was made with Achilles tendon as the graft. The experimental rabbits were euthanized 15 days after ACLR surgery, with removal of the graft, healthy anterior cruciate ligament (ACL) and Achilles tendon. The cross-sectional area and viscosity coefficient of the graft were measured, and the creep experiments were carried out under equilibrium conditions of 0.1 MPa and 1 MPa, respectively. The viscosity coefficent was calculated. Variation patterns of graft viscosity were summarize. The grafts were compared with healthy ACL. Results The cross-sectional area of the graft increased slowly within 15 days after ACLR surgery. The viscosity of ACL and graft changed nonlinearly. The viscosity coefficient was quite different under different stresses. The viscosity coefficient of the graft decreased with the time after ACLR surgery, which was more obviously under the condition of low stress. Conclusions The results are helpful to guide the implementation of early postoperative rehabilitation plan after ACLR surgery .
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AL3810, a molecular dual inhibitor of the vascular endothelial growth factor receptor (VEGFR) and fibroblast growth factor receptor (FGFR), has earned the permission of phase II clinical trial for tumor treatment by China FDA. As a reversible ATP-competitive inhibitor, AL3810 targets ATP-binding site on intracellular region of VEGFR and FGFR, whereas, AL3810 lacking interplay with extracellular region of receptors rendered deficient blood-brain tumor barrier (BBTB) recognition, poor brain penetration and unsatisfactory anti-glioma efficacy. Integrin
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Objective To study the effect of paeoniflorin on inflammatory chemokines and their receptor in a rat model of ovalbumin-induced asthma.Methods Sixty 6-week old SPF female BALB/c mice were used in this study.To es-tablish a mouse model of asthma by sensitizing and challenging with ovalbumin.ELISA was used to analyze the serum IL-6 and TNF-α, and the specific IgE against ovalbumin ( OVA-IgE ) , CCL19 and CCL21 in bronchoalveolar lavage fluid (BALF).RT-PCR was performed to determine CCR7mRNA and protein expression of chemokine receptor CCR7, and the level of NF-κB was tested by Western blot.ResultsIn In the paeoniflorin groups, the serum IL-6 and TNF-αlevels were significantly lower, and the OVA-IgE, CCL19 and CCL21 levels in BALF were significantly reduced, compared with that in the control group.CCR7mRNA and protein expression of chemokine receptor CCR7 and NF-κB in the lung were significant-ly reduced by paeoniflorin.Conclusions Paeoniflorin has a remarkably inhibitory effect on the airway inflammatory chemo-kines CCL19/CCL21 and the receptor CCR7 in the mouse model of asthma.
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BACKGROUND:Few reports are found about the effect of ovariectomized rats' bone histomorphometry parameters using non-destructive dynamic loading system.OBJECTIVE:To observe the effect of different loads situations on the bone histomorphometry parameters in ovariectomized rats.DESIGN,TIME AND SETTING:A controlled observation on the bone histomorphometry was performed in the Biomedical Engineering Laboratory of Jilin University from April 2007 to August 2007.MATERIALS:A total of 35 9-month-old Sprague-Dawley female rats were randomly divided into five groups,including sham operation group,ovariectomized (OVX) control group,OVX loading 1 N group,OVX loading 2 N group,OVX loading 4 N group.There were 7 rats in each group.METHODS:Rats in OVX control group and castration load group were processed into bilateral OVX on the back. The sham operation group only underwent the excision of fat tissues on back,and then sutured. After castration for 1 week,rats were loaded with non-destructive dynamic loading system in the two sides of the tibia,15 minutes a day. The mechanical loads would continue for 4 weeks and the loads were 1N,2N and 4N.MAIN OUTCOME MEASURES:Changes of proximal tibia bone histomorphometry parameters.RESULTS:The area,number and thickness of trabecular bone in OVX loading group were all higher than OVX control group (P＜0.05,P＜0.01).The trabecular bone area and thickness in OVX 4 N and OVX 2 N groups were significantly higher than OVX control group (P ＜ 0.001).There was a downward trend of trabecular separation in OVX 4 N group compared with OVX control group (P ＜ 0.05). With the increasing loads,there was an increasing trend of the area,number and thickness of trabecular bone,which were close to sham-operated group. The trabecular separation was declined. Single fluorescent labeled surface and double fluorescent labeled surfaces in sham operated group were all lower than that in OVX control group. With the increase in loads,the single fluorescent labeled surface,double fluorescent labeled surface,interlabeled width and mineral apposition rate had been shown to increase. The OVX 2 N and OVX 4 N groups exhibited a remarkably higher level of mineral apposition rate than OVX control group (P ＜ 0.05).CONCLUSION:With the increase in load at the range of 1-4 N,all parameters of bone histomorphometry improve in the OVX rats,the bone microstrcture is greatly ameliorated,bone mass loss is reduced and the process of osteoporosis is delayed.