| 1. |
- Pettersen, I., et al.
(författare)
-
Expression of TWEAK/Fn14 in neuroblastoma: Implications in tumorigenesis
- 2013
-
Ingår i: International Journal of Oncology. - : Spandidos Publications. - 1019-6439 .- 1791-2423. ; 42:4, s. 1239-1248
-
Tidskriftsartikel (refereegranskat)abstract
- Tumor necrosis factor-like weak inducer of apoptosis (TWEAK), a member of the tumor necrosis factor (TNF) family of cytokines, acts on responsive cells via binding to a cell surface receptor called Fn14. TWEAK binding to an Fn14 receptor or constitutive Fn14 overexpression has been shown to activate nuclear factor κB signaling which is important in tumorigenesis and cancer therapy resistance. In the present study, we demonstrate that TWEAK and Fn14 are expressed in neuroblastoma cell lines and primary tumors, and both are observed at increased levels in high-stage tumors. The treatment of neuroblastoma cell lines with recombinant TWEAK in vitro causes increased survival, and this effect is partially due to the activation of NF-κB signaling. Moreover, TWEAK induces the release of matrix metalloprotease-9 (MMP-9) in neuroblastoma cells, suggesting that TWEAK may play a role in the invasive phase of neuroblastoma tumorigenesis. TWEAK-induced cell survival was significantly reduced by silencing the TWEAK and Fn14 gene functions by siRNA. Thus, the expression of TWEAK and Fn14 in neuroblastoma suggests that TWEAK functions as an important regulator of primary neuroblastoma growth, invasion and survival and that the therapeutic intervention of the TWEAK/Fn14 pathway may be an important clinical strategy in neuroblastoma therapy.
|
|
| 2. |
- Abrahamsson, Per, 1985, et al.
(författare)
-
Analysis of mesoscale effects in high-shear granulation through a computational fluid dynamics–population balance coupled compartment model
- 2018
-
Ingår i: Particuology. - : Elsevier BV. - 2210-4291 .- 1674-2001. ; 36, s. 1-12
-
Tidskriftsartikel (refereegranskat)abstract
- There is a need for mesoscale resolution and coupling between flow-field information and the evolution of particle properties in high-shear granulation. We have developed a modelling framework that compartmentalizes the high-shear granulation process based on relevant process parameters in time and space. The model comprises a coupled-flow-field and population-balance solver and is used to resolve and analyze the effects of mesoscales on the evolution of particle properties. A Diosna high-shear mixer was modelled with microcrystalline cellulose powder as the granulation material. An analysis of the flow-field solution and compartmentalization allows for a resolution of the stress and collision peak at the impeller blades. Different compartmentalizations showed the importance of resolving the impeller region, for aggregating systems and systems with breakage. An independent study investigated the time evolution of the flow field by changing the particle properties in three discrete steps that represent powder mixing, the initial granulation stage mixing and the late stage granular mixing. The results of the temporal resolution study show clear changes in collision behavior, especially from powder to granular mixing, which indicates the importance of resolving mesoscale phenomena in time and space.
|
|
| 3. |
- Kaunisto, Erik, 1982, et al.
(författare)
-
Fundamental mechanisms for tablet dissolution: Simulation of particle deaggregation via brownian dynamics
- 2013
-
Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0022-3549 .- 1520-6017. ; 102:5, s. 1569-1577
-
Tidskriftsartikel (refereegranskat)abstract
- For disintegrating tablet formulations, deaggregation of small particles is sometimes one of the rate-limiting processes for drug release. Because the tablets contain particles that are in the colloidal size range, it may be assumed that the deaggregation process, at least qualitatively, is governed by Brownian motion and electrostatic and van der Waals interactions, where the latter two can be described by a Derjaguin–Landau–Verwey–Overbeek interaction potential. On the basis of this hypothesis, the present work investigates the applicability of Brownian dynamics (BD) simulations as a tool to understand the deaggregation mechanism on a fundamental level. BD simulations are therefore carried out to determine important deaggregation characteristics such as the so-called mean first passage time (MFPT) and first passage time distribution (FPTD) for various two-, three-, and four-particle aggregates. The BD algorithm is first validated and tuned by comparison with analytical expressions for the MFPT and FPTD in the two-particle case. It is then shown that the same algorithm can also be used for the three-particle case. Lastly, the simulations of three- and four-particle aggregates show that the initial shape of the aggregates may significantly affect the deaggregation time.
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
- Yu, X., et al.
(författare)
-
A compartmental CFD-PBM model of high shear wet granulation
- 2017
-
Ingår i: AICHE Journal. - : Wiley. - 1547-5905 .- 0001-1541. ; 63:2, s. 438-458
-
Tidskriftsartikel (refereegranskat)abstract
- © 2016 American Institute of Chemical EngineersThe conventional, geometrically lumped description of the physical processes inside a high shear granulator is not reliable for process design and scale-up. In this study, a compartmental Population Balance Model (PBM) with spatial dependence is developed and validated in two lab-scale high shear granulation processes using a 1.9L MiPro granulator and 4L DIOSNA granulator. The compartmental structure is built using a heuristic approach based on computational fluid dynamics (CFD) analysis, which includes the overall flow pattern, velocity and solids concentration. The constant volume Monte Carlo approach is implemented to solve the multi-compartment population balance equations. Different spatial dependent mechanisms are included in the compartmental PBM to describe granule growth. It is concluded that for both cases (low and high liquid content), the adjustment of parameters (e.g. layering, coalescence and breakage rate) can provide a quantitative prediction of the granulation process. © 2016 American Institute of Chemical Engineers AIChE J, 63: 438–458, 2017.
|
|
