AS1411-conjugated doxorubicin-loaded silver nanotriangles for targeted chemo-photothermal therapy of breast cancer.

Background: Combination therapy has attracted tremendous interest for its great potential in treating cancers. Materials & methods: Based on chitosan-coated silver nanotriangles, polyethylene glycol, AS1411 aptamer and doxorubicin, a multifunctional nanocomposite (AS1411-DOX-AgNTs) was constructed and characterized. Then the photothermal properties, ability to target breast cancer cells and anti-breast cancer effect of AS1411-DOX-AgNTs were evaluated. Results: AS1411-DOX-AgNTs were successfully fabricated and showed excellent photothermal conversion efficiency, breast cancer cell and tumor targeting ability. Compared with single treatments, the combination of AS1411-DOX-AgNTs with near-infrared irradiation possessed the strongest anti-breast cancer effect in vitro and in vivo. Conclusion: AS1411-DOX-AgNTs hold great potential in targeted DOX delivery and combined chemo-photothermal therapy for breast cancer.

This article focuses on nanomaterials, nanomedicine and photothermal therapy (PTT) to treat breast cancer. Nanomaterials refer to materials with at least one dimension in nanometer size (1­100 nm) or materials composed as basic units in a 3D space. Nanomedicine is the application of nanomaterials in medicine. Nanoparticles can deliver drugs to areas that are difficult for the drugs themselves to reach. PTT is a noninvasive tumor therapy that uses photothermal conversion agents to convert light energy into heat energy to kill tumor cells under the irradiation of external near-infrared (NIR) light. In recent years, combination therapy for cancers has drawn more and more attention. In the current study, we investigated the in vitro and in vivo anticancer effects of silver nanocomposites combined with chemotherapy and PTT. The prepared silver nanocomposites showed excellent physicochemical properties and possessed good anti-breast cancer efficacy combined with PTT and chemotherapy drug in vitro and in vivo. The results of this study demonstrated that these prepared silver nanocomposites had exceptional anti-breast cancer effects in combination with PTT and could be promising drug-loaded photothermal conversion agents.

A Sonic Hedgehog-Gli-Bmi1 signaling pathway plays a critical role in p27 deficiency induced bone anabolism.

To explore the mechanism of the bone anabolic action of p27 deficiency, we first confirmed that osteoblast formation and osteogenesis were significantly increased in p27 deficient mice compared with their wild-type littermates. Microarray analysis of differential gene expression profiles, followed by real-time RT-PCR and Western blots revealed that p27 deletion significantly upregulated the expression of Sonic hedgehog (Shh), Gli1 and 2 and their target gene Bmi1 in bone tissue, and significantly down regulated the expression of the negative regulators of the Shh pathway Sufu, Patched 1 and Gli3 in bone tissue. The Shh antagonist KAAD-cyclopamine or vismodegib significantly reduced osteogenesis of bone marrow mesenchymal stem cells (BM-MSCs) in vitro and osteoblastic bone formation in vivo. The results of chromatin immunoprecipitation and double luciferase assay demonstrated that p27 inhibited Shh transcription mediated via E2F4. Bmi1 knockout blocked the increase of osteoblastic bone formation induced by p27 deficiency in vivo. In conclusion, the results of this study indicate that the signaling pathway Shh-Gli-Bmi1 plays a critical role in p27 deficiency induced bone anabolic action, suggesting that Bmi1 may be an important therapeutic target for osteoporosis induced by activation of p27 signaling or inactivation of sonic hedgehog signaling.

Polymorphisms in the CYP3A5 gene significantly affect the pharmacokinetics of sirolimus after kidney transplantation.

Aim: Sirolimus (SIR) is an immunosuppressant with limitations, including a narrow treatment window, multiple adverse reactions and large differences within and among individuals. Objective: The correlation between numerous SNPs and SIR in terms of trough concentration in the early stage after kidney transplantation was analyzed. Materials & methods: A retrospective cohort study involving 69 kidney transplantation recipients was designed. Blood samples were collected to extract total DNAs, and trough SIR concentrations were measured. Logistic regression was used to analyze the association between SNPs and SIR trough concentrations. Results: At 7 days, 1 month and 3 months, the mean SIR trough concentration of patients in the CYP3A5 rs4646453-CC group was significantly higher than that in the CYP3A5 rs4646453-AA and CYP3A5 rs4646453-CA groups (p < 0.001) and CYP3A5 rs15524-AA group was significantly higher than that in the CYP3A5 rs15524-AG and CYP3A5 rs15524-GG groups (p < 0.001). Conclusion: Our study indicated that both CYP3A5 rs4646453 and CYP3A5 rs15524 had a certain influence on SIR trough concentration at 7 days, 1 month and 3 months.