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- Edvinsson, Lars
(författare)
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Novel migraine therapy with calcitonin gene-regulated peptide receptor antagonists
- 2007
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Ingår i: Expert Opinion on Therapeutic Targets. - : Informa Healthcare. - 1472-8222 .- 1744-7631. ; 11:9, s. 1179-1188
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Forskningsöversikt (refereegranskat)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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| 3. |
- Kroczak, Tadeusz J., et al.
(författare)
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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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Ingår i: Expert opinion on therapeutic targets. - : Informa Healthcare. - 1472-8222 .- 1744-7631. ; 10:2, s. 289-302
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Tidskriftsartikel (refereegranskat)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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| 5. |
- Miletic, Hrvoje, et al.
(författare)
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Anti-VEGF therapies for malignant glioma : treatment effects and escape mechanisms
- 2009
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Ingår i: Expert opinion on therapeutic targets. - : Taylor & Francis. - 1472-8222 .- 1744-7631. ; 13:4, s. 455-468
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Forskningsöversikt (refereegranskat)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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| 6. |
- Rudolfsson, Stina Häggström, et al.
(författare)
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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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Ingår i: Expert opinion on therapeutic targets. - : Informa Healthcare. - 1744-7631 .- 1472-8222. ; 13:2, s. 219-225
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Tidskriftsartikel (refereegranskat)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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