The role of interleukin-6-STAT3 signalling in glioblastoma

Glioblastoma is the most common type of malignant brain tumor among adults and is currently a non-curable disease due primarily to its highly invasive phenotype, and the lack of successful current therapies. Despite surgical resection and post-surgical treatment patients ultimately develop recurrence of the tumour. Several signalling molecules have been implicated in the development, progression and aggressiveness of glioblastoma. The present study reviewed the role of interleukin (IL)-6, a cytokine known to be important in activating several pro-oncogenic signaling pathways in glioblastoma. The current study particularly focused on the contribution of IL-6 in recurrent glioblastoma, with particular focus on glioblastoma stem cells and resistance to therapy

Inhibition of Radiation and Temozolomide-Induced Invadopodia Activity in Glioma Cells Using FDA-Approved Drugs

The most common primary central nervous system tumor in adults is the glioblastoma multiforme (GBM). The highly invasive nature of GBM cells is a significant factor resulting in the inevitable tumor recurrence and poor patient prognosis. Tumor cells utilize structures known as invadopodia to faciliate their invasive phenotype. In this study, utilizing an array of techniques, including gelatin matrix degradation assays, we show that GBM cell lines can form functional gelatin matrix degrading invadopodia and secrete matrix metalloproteinase 2 (MMP-2), a known invadopodia-associated matrix-degrading enzyme. Furthermore, these cellular activities were augmented in cells that survived radiotherapy and temozolomide treatment, indicating that surviving cells may possess a more invasive phenotype posttherapy. We performed a screen of FDA-approved agents not previously used for treating GBM patients with the aim of investigating their "anti-invadopodia" and cytotoxic effects in GBM cell lines and identified a number that reduced cell viability, as well as agents which also reduced invadopodia activity. Importantly, two of these, pacilitaxel and vinorelbine tartrate, reduced radiation/temozolomide-induced invadopodia activity. Our data demonstrate the value of testing previously approved drugs (repurposing) as potential adjuvant agents for the treatment of GBM patients to reduce invadopodia activity, inhibit GBM cell invasion, and potentially improve patient outcome

A comparison between oestradiol aptamers as receptors in CNT FET biosensors

Point of care tests for measuring the concentration of small molecules such as oestradiol are both highly desirable for healthcare and challenging to design. Field effect transistors functionalised with DNA aptamers, FET aptasensors, are a promising candidate for such tests, however, the performance of FET aptasensors does not consistently keep pace with the performance of particular aptamers in isolation. To better understand the cause of this discrepancy, we compare the performance of two oestradiol aptamers in carbon nanotube network FET aptasensors, and further characterise these aptamers using circular dichroism spectroscopy. We show that both aptamers work effectively as sensors at a much higher analyte concentration, 10−6 M, than would be predicted by published Kd values, approximately 10−8 M. We show qualitatively different behaviour between otherwise identical sensors based on the aptamer they are functionalised with, at analyte concentrations well below the limit of detection. Our results suggest that the discrepancy between predicted and realised performance of carbon nanotube network FET aptasensors has two contributing factors: the difference between the ionic environment used for sensing and the environment the aptamers have been characterised in, and the use of SELEX methods that produce aptamers with minimal structure shift on binding. To optimise the sensing response from FET aptasensors, aptamers should be selected for large structure shifts upon binding, and so that they exhibit strong binding in the ionic environment that will be used for sensing

Reduced EGFR and increased miR-221 is associated with increased resistance to temozolomide and radiotherapy in glioblastoma

Despite aggressive treatment with temozolomide and radiotherapy and extensive research into alternative therapies there has been little improvement in Glioblastoma patient survival. Median survival time remains between 12 and 15 months mainly due to treatment resistance and tumor recurrence. In this study, we aimed to explore the underlying mechanisms behind treatment resistance and the lack of success with anti-EGFR therapy in the clinic. After generating a number of treatment resistant Glioblastoma cell lines we observed that resistant cell lines lacked EGFR activation and expression. Furthermore, cell viability assays showed resistant cells were significantly less sensitive to the anti-EGFR agents when compared to parental cell lines. To further characterise the resistance mechanism in our cells microRNA prediction software identified miR-221 as a negative regulator of EGFR expression. miR-221 was up-regulated in our resistant cell lines, and this up-regulation led to a significant reduction in EGFR expression in both our cultured cell lines and a large cohort of glioblastoma patient tumor tissue

Publisher Correction to: Development of the Asia Pacific Consortium on Osteoporosis (APCO) framework: clinical standards of care for the screening, diagnosis, and management of osteoporosis in the Asia-Pacific region (Osteoporosis International, (2021), 32, 7, (1249-1275), 10.1007/s00198-020-05742-0)

10.1007/s00198-021-05953-zOsteoporosis International3271277-1278complete