147 research outputs found

    Calcium-binding protein S100P promotes tumor progression but enhances chemosensitivity in breast cancer

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    Background: Chemoresistance remains one of the obstacles to overcome in the treatment of breast cancer. S100 calcium-binding protein P (S100P) has been observed to be overexpressed in several cancers and has been associated with drug resistance, metastasis, and prognosis. However, the role of S100P in chemoresistance in breast cancer has not been thoroughly determined. Methods: Immunohistochemistry was used to evaluate the expression level of S100P protein in 22 pairs (pre-chemo and post-chemo) of breast cancer tissue from patients who underwent neoadjuvant chemotherapy. The influence of S100P on the biological behavior and chemosensitivity of breast cancer cells was then investigated. Results: The protein level of S100P in breast cancer tissue was significantly higher than in benign fibroadenoma (p<0.001). The S100P expression level was shown to be decreased by 46.55% after neoadjuvant chemotherapy (p=0.015). Subgroup analysis revealed that S100P reduction (57.58%) was mainly observed in the HER2+ tumors (p=0.027). Our in-vitro experiments showed that the knockdown of S100P suppressed the proliferation, adhesion, migration and invasion abilities of T47D and SK-BR-3 breast cancer cells. We further demonstrated that this knockdown increased the chemoresistance to paclitaxel and cisplatin in SK-BR-3 cells. We found that S100P exerted its function by activating NF-ÎșB, CCND1 and Vimentin, but downregulating E-cadherin. Conclusions: S100P promotes the aggressive properties of breast cancer cells and may be considered as a promising therapeutic target. Moreover, S100P can be used to predict the therapeutic effect of chemotherapy in HER2+ breast cancer patients

    Tim-3 promotes cell aggressiveness and paclitaxel resistance through the NF-ÎșB /STAT3 signalling pathway in breast cancer cells

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    Objective: Although T-cell immunoglobulin and mucin-domain containing molecule-3 (Tim-3) has been recognized as a promising target for cancer immunotherapy, its exact role in breast cancer has not been fully elucidated. Methods: Tim-3 gene expression in breast cancer and its prognostic significance were analyzed. Associated mechanisms were then explored in vitro by establishing Tim-3-overexpressing breast cancer cells. Results: In a pooled analysis of The Cancer Genome Atlas (TCGA) database, Tim-3 gene expression levels were significantly higher (P<0.001) in breast cancer tissue, compared with normal tissues. Tim-3 was a prognosis indicator in breast cancer patients [relapse-free survival (RFS), P=0.004; overall survival (OS), P=0.099]. Tim-3 overexpression in Tim-3low breast cancer cells promoted aggressiveness of breast cancer cells, as evidenced by enhanced proliferation, migration, invasion, tight junction deterioration and tumor-associated tubal formation. Tim-3 also enhanced cellular resistance to paclitaxel. Furthermore, Tim-3 exerted its function by activating the NF-ÎșB/STAT3 signalling pathway and by regulating gene expression [cyclin D1 (CCND1), C-Myc, matrix metalloproteinase-1(MMP1), TWIST, vascular endothelial growth factor (VEGF) upregulation, concomitant with E-cadherin downregulation). Lastly, Tim-3 downregulated tight junction-associated molecules zona occludens (ZO)-2, ZO-1 and occludin, which may further facilitate tumor progression. Conclusions: Tim-3 plays an oncogenic role in breast cancer and may represent a potential target for antitumor therapy

    ‘Emptying the cage, changing the birds’: state rescaling, path-dependency and the politics of economic restructuring in post-crisis Guangdong

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    This paper evaluates how economic restructuring in Guangdong is entwined with the politicization of state rescaling during and after the global financial crisis of 2008. It shows how a key industrial policy known as ‘double relocation’ generated tensions between the Guangdong government, then led by Party Secretary Wang Yang, and the senior echelon of the Communist Party of China in Beijing. The contestations and negotiations that ensued illustrate the dynamic entwinement between state rescaling and institutional path-dependency: the Wang administration launched this industrial policy in spite of potentially destabilizing effects on the prevailing national structure of capital accumulation. This foregrounds, in turn, the constitutive and constraining effects of established, national-level policies on local, territorially-specific restructuring policies

    SolarPACES Task III Project: Analyze Heliostat Field

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    In recent years, great efforts have been made to reach a consensus on heliostat testing best practices. A specific SolarPACES task was launched to provide a Heliostat Testing Guidelines document for single heliostat evaluation with a focus on prototype validation and qualification. Such guidelines are not well-suited for heliostat evaluation in operating commercial heliostat fields. The commercial implementation of the Central Receiver technology is burdened by the lack of a demonstrated cost-effective methodology to test solar fields, particularly during the commissioning and operation phases of the plant. To address heliostat characterization challenges, the SolarPACES funded Project Analyze Heliostat Field aims to set the basis towards a SolarPACES guideline for Heliostat Field Performance testing under a common framework. This is by means of a review of the existing methodologies, R&D and industrial stakeholders information sharing and preparation of a future quantitative comparison and validation plan. As part of the development of this project, several meetings and a workshop involving the SolarPACES community was organized to share knowledge and experience in the measurement and characterization of heliostat fields using a range of technologies and procedures. Research centers and companies from 5 different and distant countries have actively participated in these meetings, sharing their experiences, needs and interests. This paper summarizes the outcome of this international collaborative effort and the prospects for future close collaborations sustained over time

    SolarPACES Guideline for Heliostat Performance Testing - Release v1.0

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    Based on national drafts, a group of R&D and industry experts as members of the SolarPACES task III heliostat working group has been working since 2012 on the creation of a guideline for heliostat performance testing. It contains a well-defined list of parameters to describe heliostats and their performance, as well as a list for deriving these parameters. After applying the draft to several industrial and research heliostats (e.g. [1]) and iterative improvements, version 1.0 of the guideline has been released

    Photoluminescent and superparamagnetic reduced graphene oxide-iron oxide quantum dots for dual-modality imaging, drug delivery and photothermal therapy

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    Reduced graphene oxide–iron oxide quantum dots (QDs) with intrinsic photoluminescent and superparamagnetic properties were synthesized through a green, hydrothermal method that simultaneously reduced and shattered graphene nanosheets to form the dots. The structure, morphology, properties and cell viability of these QDs were investigated. The QDs emitted violet light when excited at 320 nm, possessed no residual magnetization upon magnetic hysteresis tests, and had low cytotoxicity to healthy cells at low concentrations. The suitability of the QDs for fluorescent and magnetic resonance dual-modality imaging was shown by in vitro imaging with dermal fibroblast cells and T2 relaxation time. A drug could be loaded onto the surface of the QDs, with a loading ratio of drug to QD of 0.31:1. The drug achieved a steady but full release from the QDs over 8 h: these drug-loaded QDs could be manipulated by an external magnetic stimulation for targeted drug delivery. The potential for use as a cancer photothermal therapy was demonstrated by both a rapid, ∌50 °C temperature increase by a suspension of 100 ÎŒg ml−1 of QDs and the photothermal ablation of HeLa cells in vitro under near infrared irradiation. The stability of the MGQDs in fetal calf serum was shown to improve when an ionic drug was coated on the surface

    Metabolic risk factors of cognitive impairment in young women with major psychiatric disorder

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    BackgroundCognitive performance improves clinical outcomes of patients with major psychiatric disorder (MPD), but is impaired by hyperglycemia. Psychotropic agents often induce metabolism syndrome (MetS). The identification of modifiable metabolic risk factors of cognitive impairment may enable targeted improvements of patient care.ObjectiveTo investigate the relationship between MetS and cognitive impairment in young women with MPD, and to explore risk factors.MethodsWe retrospectively studied women of 18–34 years of age receiving psychotropic medications for first-onset schizophrenia (SCH), bipolar disorder (BP), or major depressive disorder (MDD). Data were obtained at four time points: presentation but before psychotropic medication; 4–8 and 8–12 weeks of psychotropic therapy; and enrollment. MATRICS Consensus Cognitive Battery, (MCCB)—based Global Deficit Scores were used to assess cognitive impairment. Multiple logistic analysis was used to calculate risk factors. Multivariate models were used to investigate factors associated with cognitive impairment.ResultsWe evaluated 2,864 participants. Cognitive impairment was observed in 61.94% of study participants, and was most prevalent among patients with BP (69.38%). HbA1c within the 8–12 week-treatment interval was the most significant risk factor and highest in BP. Factors in SCH included pre-treatment waist circumference and elevated triglycerides during the 8–12 weeks treatment interval. Cumulative dosages of antipsychotics, antidepressants, and valproate were associated with cognitive impairment in all MPD subgroups, although lithium demonstrated a protect effect (all P &lt; 0.001).ConclusionsCognitive impairment was associated with elevated HbA1c and cumulative medication dosages. Pre-treatment waist circumference and triglyceride level at 8–12 weeks were risk factors in SCH. Monitoring these indices may inform treatment revisions to improve clinical outcomes
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