I. Componente Universitária
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Browsing I. Componente Universitária by Author "A Madureira, Patricia"
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- Corrigendum to IP1867B suppresses the insulin-like growth factor 1 receptor (IGF1R) ablating epidermal growth factor receptor inhibitor resistance in adult high grade gliomas (vol 458C, pg 29, 2019)Publication . Mihajluk, K.; Simms, C.; Reay, M.; A Madureira, Patricia; Howarth, A.; Murray, P.; Nasser, S.; Duckworth, C. A.; Pritchard, D. M.; Pilkington, G. J.; Hill, R.
- Gemcitabine-mediated tumour regression and p53-dependent gene expression: implications for colon and pancreatic cancer therapyPublication . Hill, Richard; Rabb, M.; A Madureira, Patricia; Clements, D.; Gujar, S. A.; Waisman, D. M.; Giacomantonio, C. A.; Lee, P. W. K.Gemcitabine is a chemotherapeutic that is widely used for the treatment of a variety of haematological malignancies and has become the standard chemotherapy for the treatment of advanced pancreatic cancer. Combinational gemcitabine regimes (e.g. with doxorubicin) are being tested in clinical trials to treat a variety of cancers, including colon cancer. The limited success of these trials has prompted us to pursue a better understanding of gemcitabine's mechanism of cell killing, which could dramatically improve the therapeutic potential of this agent. For comparison, we included gamma irradiation that triggers robust cell cycle arrest and Cr(VI), which is a highly toxic chemical that induces a robust p53-dependent apoptotic response. Gemcitabine induced a potent p53-dependent apoptosis that correlated with the accumulation of pro-apoptotic proteins such as PUMA and Bax. This is accompanied by a drastic reduction in p2l and 14-3-3 sigma protein levels, thereby significantly sensitizing the cells to apoptosis. In vitro and in vivo studies demonstrated that gemcitabine required PUMA transcription to instigate an apoptotic programme. This was in contrast to Cr(VI)-induced apoptosis that required Bax and was independent of transcription. An examination of clinical colon and pancreatic cancer tissues shows higher p53, p21, 14-3-3 sigma and Bax expression compared with matched normal tissues, yet there is a near absence of PUMA protein. This may explain why gemcitabine shows only limited efficacy in the treatment of these cancers. Our results raise the possibility that targeting the Bax-dependent cell death pathway, rather than the PUMA pathway, could result in significantly improved patient outcome and prognosis for these cancers.
- Retraction notice to " IP1867B suppresses the Insulin-like Growth Factor 1 Receptor (IGF1R) ablating epidermal growth factor receptor inhibitor resistance in adult high grade gliomas” [Canc. Lett., 458 (2019) pages 29–38]Publication . Mihajluk, K.; Simms, C.; Reay, M.; A Madureira, Patricia; Howarth, A.; Murray, P.; Nasser, S.; Duckworth, C.A.; Pritchard, D.M.; Pilkington, G.J.; Hill, R.This article has been retracted at the request of the Editor-in-Chief due to concerns regarding the legitimacy of images and data presented in the paper. Though a corrigendum (Can. Lett. Vol. 469, 2020, pages 524–535) was previously published to address some of these concerns, this corrigendum has also been found to contain errors and therefore cannot stand. Specific concerns are listed below.
- The role of hypoxia in glioblastoma invasionPublication . Monteiro, Ana; Hill, Richard; Pilkington, Geoffrey; A Madureira, PatriciaGlioblastoma multiforme (GBM), a grade IV astrocytoma, is the most common and deadly type of primary malignant brain tumor, with a patient's median survival rate ranging from 15 to 17 months. The current treatment for GBM involves tumor resection surgery based on MRI image analysis, followed by radiotherapy and treatment with temozolomide. However, the gradual development of tumor resistance to temozolomide is frequent in GBM patients leading to subsequent tumor regrowth/relapse. For this reason, the development of more effective therapeutic approaches for GBM is of critical importance. Low tumor oxygenation, also known as hypoxia, constitutes a major concern for GBM patients, since it promotes cancer cell spreading (invasion) into the healthy brain tissue in order to evade this adverse microenvironment. Tumor invasion not only constitutes a major obstacle to surgery, radiotherapy, and chemotherapy, but it is also the main cause of death in GBM patients. Understanding how hypoxia triggers the GBM cells to become invasive is paramount to developing novel and more effective therapies against this devastating disease. In this review, we will present a comprehensive examination of the available literature focused on investigating how GBM hypoxia triggers an invasive cancer cell phenotype and the role of these invasive proteins in GBM progression.