| 1. |
- Aldskogius, Håkan
(author)
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Regulation of microglia : potential new drug targets in the CNS.
- 2001
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In: Expert opinion on therapeutic targets. - 1472-8222 .- 1744-7631. ; 5:6, s. 655-668
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Journal article (peer-reviewed)abstract
- Microglia respond to any disturbance in the CNS which poses a threat to physiological homeostasis. Although these responses are secondary, mainly to neuronal alterations, the way the microglial response evolves in many situations promotes further damage to the CNS. The list of clinical conditions in which this situation is a major problem is continuously growing and includes neurodegenerative diseases, stroke, trauma, demyelinating disorders and neuropathic pain. The significance of microglia for the pathogenesis of neurological and neuropsychiatric conditions has led to a rapidly expanding search for therapeutic possibilities to regulate microglial activity. As will be clear from this review, treatments which are currently available appear to offer some positive effects but are still far from satisfactory. A major challenge is to understand the mechanisms that determine whether activated microglia will develop into a cytotoxic or a cytoprotective component.
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| 6. |
- Di Gennaro, A, et al.
(author)
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Targeting leukotriene B4 in inflammation
- 2014
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In: Expert opinion on therapeutic targets. - : Informa UK Limited. - 1744-7631 .- 1472-8222. ; 18:1, s. 79-93
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Journal article (peer-reviewed)
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| 7. |
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| 8. |
- Edvinsson, Lars
(author)
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Novel migraine therapy with calcitonin gene-regulated peptide receptor antagonists
- 2007
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In: Expert Opinion on Therapeutic Targets. - : Informa Healthcare. - 1472-8222 .- 1744-7631. ; 11:9, s. 1179-1188
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Research review (peer-reviewed)abstract
- Primary headaches, for example, migraine and cluster headaches represent the most prevalent neurological disorders, affecting up to 15 - 20% of the adult population. There is a clear association between head pain and the release of calcitonin gene-related peptide (CGRP). In this review the role of CGRP in human cranial circulation is described and the role for specific CGRP antagonism elucidated. It is well known that triptans (5-HT1B/1D agonist) alleviate headache in part through normalisation of CGRP levels. The central role of CGRP in migraine pathophysiology has resulted in the development of small-molecule CGRP antagonists with no cardiovascular side effects. Such compounds have high selectivity for human CGRP receptors and are efficacious in the relief of acute migraine attacks. Research indicates that they effect the abluminal side of the blood-brain barrier and that they are not vasoconstrictive, providing a new dimension in therapy.
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| 9. |
- Ekman, Simon, et al.
(author)
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Hsp90 as a therapeutic target in patients with oesophageal carcinoma
- 2010
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In: Expert opinion on therapeutic targets. - : Informa Healthcare. - 1472-8222 .- 1744-7631. ; 14:3, s. 317-328
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Research review (peer-reviewed)abstract
- Importance of the field: Oesophageal carcinoma has a poor prognosis with a 5-year overall survival rate of only 10 - 20%. The disease is often diagnosed at a late stage, when dissemination may already have occurred, contributing to the poor prognosis. However, recent developments in targeted therapy now offer new possibilities in the treatment arsenal. Heat shock protein 90 (Hsp90) has been demonstrated to protect oncogenic variants of signalling molecules from degradation, thus promoting cell growth and survival. Hsp90 has been found to be abundantly expressed in oesophageal cancer and may serve as a therapeutic target in the treatment of this disease. Areas covered in this review: We have summarised available data concerning the role of Hsp90 in oesophageal carcinoma as well as available information on other tumour types. What the reader will gain: To be able to elaborate on the molecular mechanisms of action of Hsp90 and discuss state-of-the-art of clinical trials involving Hsp90 inhibitors in malignancies, with a special emphasis on oesophageal cancer. Take home message: Preclinical studies on Hsp90 inhibition in oesophageal cancer are promising and it is anticipated that in the near future clinical trials with Hsp90 inhibitors will be initiated also for oesophageal cancer, using the experience from other trials.
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| 11. |
- Freimann, Krista, et al.
(author)
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Galanin receptors as a potential target for neurological disease
- 2015
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In: Expert opinion on therapeutic targets. - : Informa UK Limited. - 1472-8222 .- 1744-7631. ; 19:12, s. 1665-1676
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Research review (peer-reviewed)abstract
- INTRODUCTION: Galanin is a 29/30 amino acid long neuropeptide that is widely expressed in the brains of many mammals. Galanin exerts its biological activities through three different G protein-coupled receptors, GalR1, GalR2 and GalR3. The widespread distribution of galanin and its receptors in the CNS and the various physiological and pharmacological effects of galanin make the galanin receptors attractive drug targets.AREAS COVERED: This review provides an overview of the role of galanin and its receptors in the CNS, the involvement of the galaninergic system in various neurological diseases and the development of new galanin receptor-specific ligands.EXPERT OPINION: Recent advances and novel approaches in migrating the directions of subtype-selective ligand development and chemical modifications of the peptide backbone highlight the importance of the galanin neurochemical system as a potential target for drug development.
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| 16. |
- Hussain, M., et al.
(author)
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ATAD2 in cancer : a pharmacologically challenging but tractable target
- 2018
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In: Expert opinion on therapeutic targets. - : Taylor and Francis Ltd. - 1472-8222 .- 1744-7631. ; 22:1, s. 85-96
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Journal article (peer-reviewed)abstract
- Introduction: ATAD2 protein is an emerging oncogene that has strongly been linked to the etiology of multiple advanced human cancers. Therapeutically, despite the fact that genetic suppression/knockdown studies have validated it as a compelling drug target for future therapeutic development, recent druggability assessment data suggest that direct targeting of ATAD2’s bromodomain (BRD) may be a very challenging task. ATAD2’s BRD has been predicted as a ‘difficult to drug’ or ‘least druggable’ target due to the concern that its binding pocket, and the areas around it, seem to be unfeasible for ligand binding. Areas covered: In this review, after shedding light on the multifaceted roles of ATAD2 in normal physiology as well as in cancer-etiology, we discuss technical challenges rendered by ATAD2’s BRD active site and the recent drug discovery efforts to find small molecule inhibitors against it. Expert opinion: The identification of a novel low-nanomolar semi-permeable chemical probe against ATAD2’s BRD by recent drug discovery campaign has demonstrated it to be a pharmacologically tractable target. Nevertheless, the development of high quality bioavailable inhibitors against ATAD2 is still a pending task. Moreover, ATAD2 may also potentially be utilized as a promising target for future development of RNAi-based therapy to treat cancers.
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| 19. |
- Kroczak, Tadeusz J., et al.
(author)
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The emerging importance of DNA mapping and other comprehensive screening techniques, as tools to identify new drug targets and as a means of (cancer) therapy personalisation
- 2006
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In: Expert opinion on therapeutic targets. - : Informa Healthcare. - 1472-8222 .- 1744-7631. ; 10:2, s. 289-302
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Journal article (peer-reviewed)abstract
- Every human being is genetically unique and this individuality is not only marked by morphologic and physical characteristics but also by an individual's response to a particular drug. Single nucleotide polymorphisms (SNPs) are largely responsible for one's individuality. A drug may be ineffective in one patient, whereas the exact same drug may cure another patient. Recent advances in DNA mapping and other screening technologies have provided researchers and drug developers with crucial information needed to create drugs that are specific for a given individual. In the future, physicians will be able to prescribe individualised drugs adjusted to, for example, activities of specific enzymatic pathways that would either be targeted by these drugs, or would be responsible for drug conversion or inactivation. Furthermore, the mapping of the human genome allows broader development and application of drugs that act on the level of gene transcription rather than as simple biochemical inhibitors or activators of certain enzymes. Such new approaches will maximise desired therapeutic results and may completely eliminate severe side effects. To illustrate the potential of genetic translational research, the authors discuss available analytical methodologies such as; gene arrays, flow cytometry-based screening for SNPs, proteomics, metabolomics, real-time PCR, and other methods capable of detecting both SNPs, as well as more profound changes in cell metabolism. Finally, the authors provide several examples that focus mostly on targeting protein-DNA interactions, but also other processes.
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| 23. |
- Miletic, Hrvoje, et al.
(author)
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Anti-VEGF therapies for malignant glioma : treatment effects and escape mechanisms
- 2009
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In: Expert opinion on therapeutic targets. - : Taylor & Francis. - 1472-8222 .- 1744-7631. ; 13:4, s. 455-468
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Research review (peer-reviewed)abstract
- Background: Glioblastoma multiforme (GBM) has a very poor prognosis and novel treatment strategies are urgently needed. GBM appears to be an optimal target for anti-angiogenic therapy as the tumour shows a high degree of endothelial cell proliferation and pro-angiogenic growth factor expression. Objective: To examine the role of angiogenic factors (particularly VEGF) in glioma and whether inhibition of these factors can be used as a treatment.Methods: A review of relevant literature.Results/conclusions: Anti-angiogenic therapy has fulfilled the proof of concept in glioma animal models. In glioma patients, the efficacy of anti-angiogenic mono-therapies initially has been disappointing. However recent clinical trials combining bevacizumab, an anti-VEGF antibody, with chemotherapy reported very encouraging response rates. Although randomized phase III clinical trials with anti-angiogenic molecules are not yet available for GBM patients, this treatment regimen is already applied off protocol in several clinical centers. It should be kept in mind though that tumours can develop escape mechanisms. In particular invasive cells, which migrate away from the highly vascularized tumour core, are not targeted by anti-angiogenic therapies. In our opinion, the future of anti-angiogenic therapy will rely on a combination strategy including chemotherapy and drugs that target invasive glioma cells.
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| 24. |
- Nijs, Jo, et al.
(author)
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Nutritional intervention in chronic pain: an innovative way of targeting central nervous system sensitization?
- 2020
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In: Expert Opinion on Therapeutic Targets. - : Informa UK Limited. - 1472-8222 .- 1744-7631. ; 24:8, s. 793-803
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Journal article (peer-reviewed)abstract
- Introduction Few treatment programs for chronic pain nowadays take a dietary pattern or adipose status into account. Areas covered An important role of neuroinflammation in chronic pain is now well established, at least in part due to increased central nervous system glial activation. Based on preclinical studies, it is postulated that the interaction between nutrition and central sensitization is mediated via bidirectional gut-brain interactions. This model of diet-induced neuroinflammation and consequent central sensitization generates a rationale for developing innovative treatments for patients with chronic pain. Methods: An umbrella approach to cover the authors' expert opinion within an evidence-based viewpoint. Expert opinion A low-saturated fat and low-added sugar dietary pattern potentially decreases oxidative stress, preventing Toll-like receptor activation and subsequent glial activation. A low-saturated fat and low-added sugar diet might also prevent afferent vagal nerve fibers sensing the pro-inflammatory mediators that come along with a high-(saturated) fat or energy-dense dietary pattern, thereby preventing them to signal peripheral inflammatory status to the brain. In addition, the gut microbiota produces polyamines, which hold the capacity to excite N-methyl-D-aspartate receptors, an essential component of the central nervous system sensitization. Hence, a diet reducing polyamine production by the gut microbiota requires exploration as a therapeutic target for cancer-related and non-cancer chronic pain.
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| 25. |
- Rudolfsson, Stina Häggström, et al.
(author)
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Hypoxia drives prostate tumour progression and impairs the effectiveness of therapy, but can also promote cell death and serve as a therapeutic target.
- 2009
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In: Expert opinion on therapeutic targets. - : Informa Healthcare. - 1744-7631 .- 1472-8222. ; 13:2, s. 219-225
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Journal article (peer-reviewed)abstract
- Hypoxia is common in prostate tumours, promoting tumour progression and impairing treatment responses. Hypoxia stimulates angiogenesis but blood vessels formed in tumours are functionally abnormal so the tissue remains hypoxic. Castration treatment is the standard therapy for advanced prostate cancer. In non-malignant prostate tissue castration-induced epithelial cell death is in part mediated by vascular insult and acute hypoxia, but in prostate tumours the cell death response is less prominent and the tumours will eventually relapse. The effect of androgen ablation therapy should therefore be enhanced by additional targeting of the vasculature and hypoxic tumour cells. However if castration fails to kill a sufficiently large number of cells it could by inducing hypoxia make the situation worse. Androgen ablation treatment, may, after the initial vascular insult, result in temporary vascular normalisation and transiently increased tissue oxygen levels. During this time window, which needs to be better defined, the efficacy of cytotoxic drug and radiation treatments are probably enhanced. In order to allow development of more effective treatment strategies for advanced prostate cancer we need to understand the role of hypoxia in prostate cancer progression and treatment responses. With this knowledge we can properly tailor and time additional treatments with androgen ablation.
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| 29. |
- Steffensen, KR, et al.
(author)
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Targeting liver X receptors in inflammation
- 2013
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In: Expert opinion on therapeutic targets. - : Informa Healthcare. - 1744-7631 .- 1472-8222. ; 17:8, s. 977-990
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Journal article (peer-reviewed)
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