| 1. |
- Adrian, Gabriel, et al.
(författare)
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In vitro assays for investigating the FLASH effect
- 2022
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Ingår i: Expert Reviews in Molecular Medicine. - : Cambridge University Press (CUP). - 1462-3994. ; 24
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Forskningsöversikt (refereegranskat)abstract
- FLASH radiotherapy is a novel technique that has been shown in numerous preclinical in vivo studies to have the potential to be the next important improvement in cancer treatment. However, the biological mechanisms responsible for the selective FLASH sparing effect of normal tissues are not yet known. An optimal translation of FLASH radiotherapy into the clinic would require a good understanding of the specific beam parameters that induces a FLASH effect, environmental conditions affecting the response, and the radiobiological mechanisms involved. Even though the FLASH effect has generally been considered as an in vivo effect, studies finding these answers would be difficult and ethically challenging to carry out solely in animals. Hence, suitable in vitro studies aimed towards finding these answers are needed. In this review, we describe and summarise several in vitro assays that have been used or could be used to finally elucidate the mechanisms behind the FLASH effect.
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| 2. |
- Andersson, Per-Ola, 1964, et al.
(författare)
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Chronic idiopathic thrombocytopenic purpura (ITP): molecular mechanisms and implications for therapy.
- 2004
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Ingår i: Expert reviews in molecular medicine. - 1462-3994. ; 6:24, s. 1-17
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Tidskriftsartikel (refereegranskat)abstract
- Chronic idiopathic thrombocytopenic purpura (ITP) is an immune-mediated disorder in which platelets are prematurely destroyed in the reticuloendothelial system by platelet autoantibodies. However, it is becoming clear that the pivotal process of the humoral immune response in the pathogenesis of the disorder is a complex interaction between antigen-presenting cells, T cells and B cells. Furthermore, it is increasingly evident that regulatory T cells play an important role and that T-cell-mediated cytotoxicity contributes to the destruction of platelets in ITP. Different new approaches to immunotherapy in chronic ITP have been explored, including use of anti-CD20, anti-CD154 and anti-CD52 antibodies. So far, these therapies have been antigen-nonspecific and the risk of general immunosuppression is a concern. Thus, improving our understanding of the interaction and relative contribution of humoral and cell-mediated mechanisms is essential for developing antigen-specific immunotherapies for the treatment of this disorder. This review aims to elucidate the current status of knowledge of the cellular and humoral immune components of chronic ITP, together with the implications of this knowledge for therapy.
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| 3. |
- Dillner, Joakim, et al.
(författare)
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Can genital-tract human papillomavirus infection and cervical cancer be prevented with a vaccine?
- 2004
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Ingår i: Expert Reviews in Molecular Medicine. - 1462-3994. ; 2004, s. 1-21
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Tidskriftsartikel (refereegranskat)abstract
- Human papillomavirus (HPV) infection is the cause of squamous cell carcinoma of the uterine cervix. This causative relationship has provided the rationale and incentive for development of a prophylactic vaccine. Such a vaccine, if found to be effective, could reduce the need for cervical cancer screening and have a profound effect on the incidence of cervical and other anogenital cancers. This review begins by examining the basic biological and epidemiological principles relevant to the development of HPV preventative vaccines. It then summarises studies examining the use of vaccines to prevent HPV infection in animals and humans, and, finally, discusses some of the unanswered issues surrounding vaccine development against HPV infection and cervical cancer.
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| 4. |
- Gil-Bea, FJ, et al.
(författare)
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Insights into the mechanisms of copper dyshomeostasis in amyotrophic lateral sclerosis
- 2017
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Ingår i: Expert reviews in molecular medicine. - : Cambridge University Press (CUP). - 1462-3994. ; 19, s. e7-
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Tidskriftsartikel (refereegranskat)abstract
- Amyotrophic lateral sclerosis (ALS) is a severe neuromuscular disease characterised by a progressive loss of motor neurons that usually results in paralysis and death within 2 to 5 years after disease onset. The pathophysiological mechanisms involved in ALS remain largely unknown and to date there is no effective treatment for this disease. Here, we review clinical and experimental evidence suggesting that dysregulation of copper homeostasis in the central nervous system is a crucial underlying event in motor neuron degeneration and ALS pathophysiology. We also review and discuss novel approaches seeking to target copper delivery to treat ALS. These novel approaches may be clinically relevant not only for ALS but also for other neurological disorders with abnormal copper homeostasis, such as Parkinson's, Huntington's and Prion diseases.
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| 5. |
- Hjalt, Tord, et al.
(författare)
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Current molecular understanding of Axenfeld-Rieger syndrome.
- 2005
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Ingår i: Expert Reviews in Molecular Medicine. - 1462-3994. ; 7:25, s. 1-17
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Forskningsöversikt (refereegranskat)abstract
- Axenfeld-Rieger syndrome (ARS) is a rare autosomal dominant inherited disorder affecting the development of the eyes, teeth and abdomen. The syndrome is characterised by complete penetrance but variable expressivity. The ocular component of the ARS phenotype has acquired most clinical attention and has been dissected into a spectrum of developmental eye disorders, of which open-angle glaucoma represents the main challenge in terms of treatment. Mutations in several chromosomal loci have been implicated in ARS, including PITX2, FOXC1 and PAX6. Full-spectrum ARS is caused primarily by mutations in the PITX2 gene. The homeobox transcription factor PITX2 is produced as at least four different transcriptional and splicing isoforms, with different biological properties. Intriguingly, PITX2 is also involved in left-right polarity determination, although asymmetry defects are not a feature of ARS. In experimental animal models and in cell culture experiments using PITX2, abundant evidence indicates that a narrow window of expression level of this gene is vital for its correct function.
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| 6. |
- Iranpour, Mahmoud, et al.
(författare)
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Apoptosis, autophagy and unfolded proteinresponse pathways in Arbovirus replicationand pathogenesis
- 2016
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Ingår i: Expert Reviews in Molecular Medicine. - Cambridge University Press : Cambridge University Press (CUP). - 1462-3994. ; 18:e1, s. 21-
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Forskningsöversikt (refereegranskat)abstract
- Arboviruses are pathogens that widely affect the health of people in different communities around the world. Recently, a few successful approaches toward production of effective vaccines against some of these pathogens have been developed, but treatment and prevention of the resulting diseases remain a major health and research concern. The arbovirus infection and replication processes are complex, and many factors are involved in their regulation. Apoptosis, autophagy and the unfolded protein response (UPR) are three mechanisms that are involved in pathogenesis of many viruses. In this review, we focus on the importance of these pathways in the arbovirus replication and infection processes. We provide a brief introduction on how apoptosis, autophagy and the UPR are initiated and regulated, and then discuss the involvement of these pathways in regulation of arbovirus pathogenesis.
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| 7. |
- Llona-Minguez, S, et al.
(författare)
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Chemical strategies for development of ATR inhibitors
- 2014
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Ingår i: Expert reviews in molecular medicine. - : Cambridge University Press (CUP). - 1462-3994. ; 16, s. e10-
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Tidskriftsartikel (refereegranskat)abstract
- ATR protein kinase is one of the key players in maintaining genome integrity and coordinating of the DNA damage response and repair signalling pathways. Inhibition of ATR prevents signalling from stalled replication forks and enhances the formation of DNA damage, particularly under conditions of replication stress present in cancers. For this reason ATR/CHK1 checkpoint inhibitors can potentiate the effect of DNA cross-linking agents, as evidenced by ATR inhibitors recently entering human clinical trials. This review aims to compile the existing literature on small molecule inhibitors of ATR, both from academia and the pharmaceutical industry, and will provide the reader with a comprehensive summary of this promising oncology target.
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| 8. |
- Lu, Qianqian, et al.
(författare)
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Ebselen, a multi-target compound : its effects on biological processes and diseases
- 2021
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Ingår i: Expert Reviews in Molecular Medicine. - : Cambridge University Press. - 1462-3994. ; 23
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Forskningsöversikt (refereegranskat)abstract
- Ebselen is a well-known synthetic compound mimicking glutathione peroxidase (GPx), which catalyses some vital reactions that protect against oxidative damage. Based on a large number of in vivo and in vitro studies, various mechanisms have been proposed to explain its actions on multiple targets. It targets thiol-related compounds, including cysteine, glutathione, and thiol proteins (e.g., thioredoxin and thioredoxin reductase). Owing to this, ebselen is a unique multifunctional agent with important effects on inflammation, apoptosis, oxidative stress, cell differentiation, immune regulation and neurodegenerative disease, with anti-microbial, detoxifying and anti-tumour activity. This review summarises the current understanding of the multiple biological processes and molecules targeted by ebselen, and its pharmacological applications.
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| 9. |
- Unterlass, JE, et al.
(författare)
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Warburg and Krebs and related effects in cancer
- 2019
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Ingår i: Expert reviews in molecular medicine. - : Cambridge University Press (CUP). - 1462-3994. ; 21, s. e4-
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Tidskriftsartikel (refereegranskat)abstract
- Warburg and coworkers' observation of altered glucose metabolism in tumours has been neglected for several decades, which, in part, was because of an initial misinterpretation of the basis of their finding. Following the realisation that genetic alterations are often linked to metabolism, and that the tumour micro-environment imposes different demands on cancer cells, has led to a reinvestigation of cancer metabolism in recent years. Increasing our understanding of the drivers and consequences of the Warburg effect in cancer and beyond will help to identify new therapeutic strategies as well as to identify new prognostic and therapeutic biomarkers. Here we discuss the initial findings of Warburg and coworkers regarding cancer cell glucose metabolism, how these studies came into focus again in recent years following the discovery of metabolic oncogenes, and the therapeutic potential that lies within targeting the altered metabolic phenotype in cancer. In addition, another essential nutrient in cancer metabolism, glutamine, will be discussed.
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| 10. |
- Williams, ST, et al.
(författare)
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Precision oncology using ex vivo technology: a step towards individualised cancer care?
- 2022
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Ingår i: Expert reviews in molecular medicine. - : Cambridge University Press (CUP). - 1462-3994. ; 24, s. e39-
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Tidskriftsartikel (refereegranskat)abstract
- Despite advances in cancer genomics and the increased use of genomic medicine, metastatic cancer is still mostly an incurable and fatal disease. With diminishing returns from traditional drug discovery strategies, and high clinical failure rates, more emphasis is being placed on alternative drug discovery platforms, such as ex vivo approaches. Ex vivo approaches aim to embed biological relevance and inter-patient variability at an earlier stage of drug discovery, and to offer more precise treatment stratification for patients. However, these techniques also have a high potential to offer personalised therapies to patients, complementing and enhancing genomic medicine. Although an array of approaches are available to researchers, only a minority of techniques have made it through to direct patient treatment within robust clinical trials. Within this review, we discuss the current challenges to ex vivo approaches within clinical practice and summarise the contemporary literature which has directed patient treatment. Finally, we map out how ex vivo approaches could transition from a small-scale, predominantly research based technology to a robust and validated predictive tool. In future, these pre-clinical approaches may be integrated into clinical cancer pathways to assist in the personalisation of therapy choices and to hopefully improve patient experiences and outcomes.
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