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Background: Hypoxia-activated prodrug (HAP) is a promising candidate for highly tumor-specific chemotherapy. However, the oxygenation heterogeneity and dense extracellular matrix (ECM) of tumor, as well as the potential resistance to chemotherapy, have severely impeded the resulting overall efficacy of HAP. Results: A HAP potentiating strategy is proposed based on ultrasound responsive nanodroplets (PTP@PLGA), which is composed of protoporphyrin (PpIX), perfluoropropane (PFP) and a typical HAP, tirapazamine (TPZ). The intense vaporization of PFP upon ultrasound irradiation can magnify the sonomechanical effect, which loosens the ECM to promote the penetration of TPZ into the deep hypoxic region. Meanwhile, the PpIX enabled sonodynamic effect can further reduce the oxygen level, thus activating the TPZ in the relatively normoxic region as well. Surprisingly, abovementioned ultrasound effect also results in the downregulation of the stemness of cancer cells, which is highly associated with drug-refractoriness. Conclusions: This work manifests an ideal example of ultrasound-based nanotechnology for potentiating HAP and also reveals the potential acoustic effect of intervening cancer stem-like cells. [ABSTRACT FROM AUTHOR]

Background: Accumulating evidence suggests that dysregulated snoRNA may play a role in the development of malignancy. In the present study, we investigated the role of SNORD78 in the tumorigenesis of non-small cell lung cancer (NSCLC). Methods: We determined the expression level of SNORD78 in NSCLC tissues with quantitative real-time PCR and then studied its clinical significance. We explored the biological significance of SNORD78 with gain-and-loss-of-function analyses both in vitro and in vivo. Results: A great upregulation of SNORD78 was observed in cancer tissues compared to their adjacent normal tissues. Meanwhile, patients with high SNORD78 expression have significantly poorer prognosis than those with low expression. Inhibition of SNORD78 suppressed the proliferation of NSCLC cells via inducing G0/G1 cell cycle arrest and apoptosis while SNORD78 overexpression promoted the cell proliferation. SNORD78 promoted invasion of NSCLC cells via inducing epithelial-mesenchymal-transition (EMT). SNORD78 was also obviously upregulated in cancer stem-like cells and is required for the self-renewal of NSCLC. The oncogenic activity of SNORD78 was also confirmed with in vivo data. Conclusion: Our study identified that SNORD78 may be a potential therapeutic target for NSCLC. [ABSTRACT FROM AUTHOR]

Background: This study is to explore the pathological features of transplanted tumor established by CD133 positive TJ905 glioblastoma stem-like cells. Methods: CD133 positive TJ905 glioma cells were separated by immunomagnetic beads to isolate glioma stem-like cells. TJ905 cells and stem-like cells were inoculated subcutaneously into the mice to establish model of transplanted tumor, respectively. Mice growing condition and behavior were observed. HE staining assay, immunohistochemical assay for GFAP, Ki-67 and Olig-2, and CD34 marked microvascular density (MVD) test were performed. Results: The growing condition and behavior of mice in TJ905 stem cell group was more exaggerated and the models showed stronger malignant features pathologically than that in TJ905 cell group. Glial fibrillary acidic protein (GFAP) in TJ905 cell and stem-like cell group showed the transplanted tumor originated from astrocytes. Expression of Ki-67 and oligodendrocyte transcription factor-2 (Olig-2) in TJ905 stem cells was higher notably and CD34 expression in stem cell group was significantly higher than that in the other two groups. Conclusions: Pathological features of transplanted tumor established by CD133 positive glioblastoma stem-like cells show more malignant. Use of TJ905 stem cells to establish transplanted tumor model in nude mice is excellent for glioma research. [ABSTRACT FROM AUTHOR]