21 research outputs found
Comprehensive lung injury pathology induced by mTOR inhibitors
Molecular Targets in Oncology[Abstract] Interstitial lung disease is a rare side effect of temsirolimus treatment in renal cancer patients. Pulmonary fibrosis is characterised by the accumulation of extracellular matrix collagen, fibroblast proliferation and migration, and loss of alveolar gas exchange units. Previous studies of pulmonary fibrosis have mainly focused on the fibro-proliferative process in the lungs. However, the molecular mechanism by which sirolimus promotes lung fibrosis remains elusive. Here, we propose an overall cascade hypothesis of interstitial lung diseases that represents a common, partly underlying synergism among them as well as the lung pathogenesis side effects of mammalian target of rapamycin inhibitors
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PRP-1 significantly decreases the [ALDH.sup.high] cancer stem cell population and regulates the aberrant Wnt/[beta]-catenin pathway in human chondrosarcoma JJ012 cells
Chondrosarcomas are malignant bone tumors refractory to chemotherapy and radiation treatment; thus, novel therapeutic strategies are required. Proline-rich poly-peptide 1 (PRP-1) has previously demonstrated antitumor properties in chondrosarcoma. To further investigate the role of PRP-1 in chondrosarcoma cells, its effects on cancer stem cell (CSC) populations were determined by analyzing aldehyde dehydrogenase (ALDH) activity, an established marker of CSCs, in association with regulation of the Wnt/[beta]-catenin signaling. A significant decrease in [ALDH.sup.high] CSCs was observed following treatment of chondrosarcoma JJ012 cells with PRP-1. For [RT.sup.2] profiler PCR array analysis of Wnt/[beta]-catenin signaling genes, cells were sorted into: i) Bulk JJ012 cells; ii) [ALDH.sup.high] cells sorted from untreated JJ012 cells ([ALDH.sup.high-untreated]); and iii) [ALDH.sup.low] cells sorted from PRP-1-treated JJ012 cells ([ALDH.sup.low-PRP-1]). The expression levels of Wnt/[beta]-catenin signaling genes were determined to be downregulated in the [ALDH.sup.high-untreated] cells and upregulated in [ALDH.sup.low-PRP-1] cells when compared to the bulk JJ012 cells. Additionally, two important oncogenes involved in this pathway, MMP7 and CCND2, were found to be down-regulated in the [ALDH.sup.low-PRP-1] cells. Immunocytochemistry demonstrated the localization of [beta]-catenin in the nuclei of the PRP-1-treated cells. Western blotting indicated increased [beta] -catenin expression in the [ALDH.sup.low-PRP-1] cells compared with the bulk JJ012 cells. Analysis of the cytoplasmic and nuclear fractions of cells treated with increasing concentrations of PRP-1 and [beta]-catenin nuclear translocation inhibitor CGP57380, suggested the nuclear translocation of [beta]-catenin following PRP-1 treatment. In addition, treatment of JJ012 cells with a specific ALDH inhibitor, diethylaminobenzaldehyde, and PRP-1 resulted in a significant decrease in cytoplasmic [beta]-catenin protein expression. This indicated that ALDH inactivation may be associated with the nuclear translocation of [beta]-catenin. Derivation of sarcomas from mesenchymal stem cells via inactivation of the Wnt pathway has been previously documented. The findings of the present study support the notion that Wnt/[beta]-catenin activation may serve a differential role in sarcomas, limiting tumor progression in association with decreased CSC activity.Academi
Left Ventricular Pressure Measurement by Telemetry Is an Effective Means to Evaluate Transplanted Heart Function in Experimental Heterotopic Cardiac Xenotransplantation
Surgical and Nonsurgical Complications of a Pig to Baboon Heterotopic Heart Transplantation Model
Transient third nerve palsy after electrometallicthrombosis of carotid cavernous fistulae.
Increasing lifetime of recurrent sunspot groups within the Greenwich photoheliographic results
Long-lived (> 20 days) sunspot groups extracted from the Greenwich Photoheliographic Results (GPR) are examined for evidence of decadal change. The problem of identifying sunspot groups that are observed on consecutive solar rotations (recurrent sunspot groups) is tackled by first constructing manually an example dataset of recurrent sunspot groups and then using machine learning to generalise this subset to the whole GPR. The resulting dataset of recurrent sunspot groups is verified against previous work by A. Maunder and other Royal Greenwich Observatory (RGO) compilers. Recurrent groups are found to exhibit a slightly larger value for the Gnevyshev -aEuro parts per thousand Waldmeier Relationship than the value found by Petrovay and van Driel-Gesztelyi (Solar Phys. 51, 25, 1977), who used recurrence data from the Debrecen Photoheliographic Results. Evidence for sunspot-group lifetime change over the previous century is observed within recurrent groups. A lifetime increase of a factor of 1.4 between 1915 and 1940 is found, which closely agrees with results from Blanter et al. (Solar Phys. 237, 329, 2006). Furthermore, this increase is found to exist over a longer period (1915 to 1950) than previously thought and provisional evidence is found for a decline between 1950 and 1965. Possible applications of machine-learning procedures to the analysis of historical sunspot observations, the determination of the magnetic topology of the solar corona and the incidence of severe space-weather events are outlined briefly