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Chen B.,University of Sichuan | Zhang W.,University of Sichuan | Zhang W.,Chongqing Medical University | Gao J.,Centers for Disease Control and Prevention | And 10 more authors.
Cancer Letters | Year: 2014

Ribosomal protein S6 (rpS6), a component of the small 40S ribosomal subunit, has been found to be associated with multiple physiological and pathophysiological functions. However, its effects and mechanisms in non-small cell lung cancer (NSCLC) still remain unknown. Here, we showed that expressions of total rpS6 and phosphorylation rpS6 (p-rpS6) were both significantly overexpressed in NSCLC. Further survival analysis revealed the shortened overall survival (OS) and relapse-free survival (RFS) in p-rpS6 overexpressed patients and confirmed it as an independent adverse predictor. Stable downregulation of rpS6 in lung adenocarcinoma A549 and squamous cell carcinoma H520 cell lines was then achieved by two specific small hairpin RNA (shRNA) lentiviruses separately. Subsequent experiments showed that downregulation of rpS6 dramatically inhibited cell proliferation in vitro and tumorigenicity in vivo. Moreover, loss of rpS6 promoted cells arrested in G0-G1 phase and reduced in G2-M phase, along with the expression alterations of relative proteins. However, no notable change in apoptosis was observed. Collectively, these results suggested that rpS6 is overactivated in NSCLC and its downregulation suppresses the growth of NSCLC mainly by inducing G0-G1 cell cycle arrest rather than apoptosis. © 2014 Elsevier Ireland Ltd.

Zhu Y.,Sichuan Academy of Medical Science and oSichuan Provincial Peoples Hospital | Karakhanova S.,University of Heidelberg | Huang X.,Sichuan Academy of Medical Science and oSichuan Provincial Peoples Hospital | Deng S.P.,Sichuan Academy of Medical Science and oSichuan Provincial Peoples Hospital | And 3 more authors.
Experimental Cell Research | Year: 2014

The cytokine interferon-α (IFNα) belongs to the group of type I interferons already used in cancer therapy. This drug possesses radio- and chemo-sensitizing, and shows anti-angiogenic properties. Cancer stem cells (CSC) are a unique population of tumor cells that initiate secondary tumors, and are responsible for metastasis formation. Patients with pancreatic ductal adenocarcinoma (PDAC) have an especially poor prognosis, with 5-year survival rates of only ~1% and median survival of 4-6 months. PDAC is characterized by the presence of CSC. In this work we demonstrate for the first time that IFNα up-regulates the expression of the CSC markers CD24, CD44 and CD133 in in vitro and in vivo models of PDAC. We showed the IFNα effects on the migration and invasion of PDAC cells, which is associated with the level of the CSC marker expression. In vivo, this drug inhibits tumor growth but promotes metastasis formation in the early stage of tumor growth. We propose that IFNα may enhance the enrichment of CSC in PDAC tumors. Additionally we also suggest that in combination therapy of solid tumors with IFNα, this drug should be given to patients prior to chemotherapy to achieve the CSC activation. © 2014 Elsevier Inc.

Wang J.,Southwest Jiaotong University | Yang G.,Southwest Jiaotong University | Guo X.,Southwest Jiaotong University | Tang Z.,Southwest Jiaotong University | And 2 more authors.
Biomaterials | Year: 2014

Biodegradable polyanhydrides possess unique features like those that they can predominantly undergo surface erosion, and the payloads can be released by a steady speed. However, there is little work that has been published to describe the polyanhydride micelles with redox-responsiveness as a nanocarrier for drug delivery. In this study, we develop one type of new amphiphilic polyanhydride copolymer containing disulfide bonds between the hydrophilic and hydrophobic segments. The copolymer can self-assemble into stable micelles with well-defined core-shell structure and a uniform size distribution with an average diameter of 69 nm. The disassembly behaviors of the micelles triggered by glutathione are evaluated from the changes of the micellar size, morphology and molecular weight. An approximate zero-order in vitro drug release mode with a fast speed can be achieved in a reducing and acid environment similar with that of tumor cells. In vitro cytotoxicity analysis demonstrate that the Cur-loaded micelles are of great efficiency in inhibiting the growth of cancer cells due to the rapidly intracellular delivery of therapeutic agent. Both the qualitative and quantitative results of the antitumor activity in 4T1 tumor-bearing BALB/c mice reveal that the redox-responsive micelles have a more significant therapeutic effect to artificial solid tumor compared to the redox-insensitive micelles. This study provides a new insight into the biomedical application of polyanhydrides in drug delivery. © 2013 Elsevier Ltd.

Hu J.,Sichuan Academy of Medical science and oSichuan Provincial Peoples Hospital | Yao B.,University of Sichuan | Yang X.,Sichuan Academy of Medical science and oSichuan Provincial Peoples Hospital | Ma F.,University of Sichuan | Ma F.,Chinese University of Hong Kong
Medical Hypotheses | Year: 2015

The quality of the bone-tendon healing is very important to the surgery outcome after anterior cruciate ligament reconstruction. The necrosis of autograft and local new blood vessels occur after the surgery. The fibroblasts and mesenchymal cells presenting in the tendon-bone interface as well as the infiltrated of neutrophils and macrophages improve the biomechanical properties of the healing. We hypothesize that immunosuppressive effect of Siglecs which present on the surface of neutrophils and macrophages play the important roles to regulate acute local inflammatory reaction, maintain the physiological environment and induce the differentiation of the pluripotent cells to form the accepted histologic structure healing of the tendon-bone interface. It might be helpful to understand the mechanism of tendon-bone healing. © 2014 Elsevier Ltd.

Yang X.,Sichuan Academy of Medical science and oSichuan Provincial Peoples Hospital | Ma F.,University of Sichuan
Medical Hypotheses | Year: 2014

Microwave diathermy is a recommended physicotherapeutics commonly for the cases in treating inflammatory arthritis and improving the post-operative complications, which could help the synovial's fluid of the joints recover to being physiological status. Sialylation of the components especially on the glycan proteins and cell surface in the synovial fluid plays the key role for the joints normal function including lubrication and local inflammation. Here, we proposed that natural thermal radiation of microwave facilitate the local hemangiectasis and aid the balance of sialylation and desialylation of the synovin and cell surfaces in the joint fluid which might contribute to alleviate local joint symptom and assist joint functional recovery. © 2014 Elsevier Ltd.

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