| 1. |
- Arnberg, Niklas
(författare)
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Adenovirus receptors : implications for targeting of viral vectors
- 2012
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Ingår i: TIPS - Trends in Pharmacological Sciences. - : Elsevier. - 0165-6147 .- 1873-3735. ; 33:8, s. 442-448
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Forskningsöversikt (refereegranskat)abstract
- Cancer, cardiovascular disease, and infectious diseases are all global health threats. To combat these diseases with gene therapies, adenovirus-based vectors have been developed. Although certain clinical trials appear successful, there is an obvious need to improve the efficacy of most adenovirus-based vectors. For the most commonly used vector (based on type 5; Ad5), a main problem is its accumulation in the liver, which can be attributed to interactions with specific host factors. The diverse tropism for types other than Ad5 implies that vectors based on alternative types could have advantages. The numerous interactions of different adenoviruses with host molecules - such as the recently identified desmoglein-2 receptor - may cause novel and unexpected obstacles, but also may provide possibilities for vectors based on alternative types. This review provides an update of new and previously known molecules that mediate cellular attachment of human adenoviruses and discusses how these may influence the targeting of adenovirus-based vectors.
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| 2. |
- Evers, Bastiaan, et al.
(författare)
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Targeting homologous recombination repair defects in cancer
- 2010
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Ingår i: TIPS - Trends in Pharmacological Sciences. - : Elsevier BV. - 0165-6147 .- 1873-3735. ; 31:8, s. 372-380
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Forskningsöversikt (refereegranskat)abstract
- DNA repair is essential for cells to maintain genome stability in an environment that constantly produces DNA damage. There is a growing appreciation that defects in homologous recombination repair underlie hereditary and sporadic tumourigenesis, and that deficiency in this pathway may dictate the sensitivity of tumours to certain DNA-damaging agents. Homologous recombination deficiency (HRD) may therefore prove to be a diagnostic criterion per se if appropriate biomarkers become available to identify these tumours. In addition, homologous recombination-deficient tumours are more sensitive to inhibition of other DNA repair pathways through so-called 'synthetic lethal interactions', a principle that is currently being tested in clinical trials. Finally, homologous recombination repair-deficient cells may have an increased dependency on certain cell-cycle checkpoints, which can be therapeutically exploited. Here we describe recent advances in strategies to identify and target HRD tumours, approaches to overcome resistance, and combinatory strategies to optimize treatment outcome.
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| 3. |
- Fowler, Christopher J.
(författare)
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Anandamide uptake explained?
- 2012
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Ingår i: TIPS - Trends in Pharmacological Sciences. - : Elsevier BV. - 0165-6147 .- 1873-3735. ; 33:4, s. 181-185
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Forskningsöversikt (refereegranskat)abstract
- The endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol are removed from the extracellular space by a process of cellular uptake followed by metabolism. Although the enzymes responsible for endocannabinoid metabolism have been well characterised, the processes involved in uptake have been the subject of much controversy. Recent studies, however, have identified intracellular transport proteins (fatty acid binding proteins 5 and 7, heat shock protein 70, albumin, and fatty acid amide hydrolase-like AEA transporter protein) that shuttle AEA from the plasma membrane to its metabolic enzymes. Proteins such as the fatty acid amide hydrolase-like anandamide transporter protein may be useful targets for novel therapeutic strategies aimed at potentiating AEA signalling. In this article I review the current state of the art of endocannabinoid uptake.
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| 4. |
- Fowler, Christopher J.
(författare)
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Has FLAT fallen flat?
- 2014
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Ingår i: TIPS - Trends in Pharmacological Sciences. - : Elsevier BV. - 0165-6147 .- 1873-3735. ; 35:2, s. 51-52
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 5. |
- Fowler, Christopher J.
(författare)
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NSAIDs : eNdocannabinoid stimulating anti-inflammatory drugs?
- 2012
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Ingår i: TIPS - Trends in Pharmacological Sciences. - : Elsevier BV. - 0165-6147 .- 1873-3735. ; 33:9, s. 468-473
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Forskningsöversikt (refereegranskat)abstract
- Read any pharmacology textbook and the message is clear: nonsteroidal anti-inflammatory drugs (NSAIDs) act by inhibiting the activity of cyclooxygenase (COX) and thereby the production of prostaglandins. However, evidence is accumulating that NSAIDs involve the endocannabinoid system in their actions, and that such effects may pave the way towards the design of new analgesics that are not plagued with the gastrointestinal and cardiovascular adverse actions that are associated with this class of drugs. In this Opinion article, our current understanding of the involvement of the endocannabinoid system in the actions of NSAIDs is described, and the ways in which this can lead to novel drug development is discussed.
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| 6. |
- Högberg, Liselotte Diaz, et al.
(författare)
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The global need for effective antibiotics : challenges and recent advances
- 2010
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Ingår i: TIPS - Trends in Pharmacological Sciences. - : Elsevier BV. - 0165-6147 .- 1873-3735. ; 31:11, s. 509-515
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Forskningsöversikt (refereegranskat)abstract
- The emerging problem of antibiotic resistance is a serious threat to global public health. The situation is aggravated by a substantial decline in the research and development of antibacterial agents. Hence, very few new antibacterial classes are brought to market when older classes lose their efficacy. There has been renewed and growing attention within policy groups to: (i) address the problem; (ii) discuss incentives for the development of urgently needed new treatments; (iii) preserve the efficacy of existing therapeutic options. We briefly review the basic principles of antibiotic resistance, and contrast the increasing resistance to the dwindling antibacterial 'pipeline'. We also highlight some recent policy initiatives aiming to secure the future need of effective antibiotics.
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| 7. |
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| 8. |
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| 9. |
- Järver, Peter, et al.
(författare)
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In vivo biodistribution and efficacy of peptide mediated delivery
- 2010
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Ingår i: TIPS - Trends in Pharmacological Sciences. - : Elsevier BV. - 0165-6147 .- 1873-3735. ; 31:11, s. 528-535
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Forskningsöversikt (refereegranskat)abstract
- To transverse the plasma membrane and gain access to the cellular interior is one of the major obstacles for many novel pharmaceutical molecules. Since the late 1990 s, cell-penetrating peptides (CPPs) have been utilized as transport vectors for a broad spectrum of 'biological cargoes', ranging from inert gold particles to multifaceted macromolecules such as proteins and plasmids. Numerous studies have shown that CPPs are efficient carriers for bioactive cargoes in vitro. However, even though CPPs are versatile transport vectors, this does not guarantee they can be developed into useful pharmaceutical molecules. Nevertheless, recent progress in the field has shown CPPs to be effective for in vivo delivery with retained biological activity of a wide variety of bioactive cargoes into virtually any mammalian tissue. This review will focus on recent developments and applications for CPP delivery and distribution in vivo.
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| 10. |
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