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The interest in magnetic fluid hyperthermia (MFH) and cancer therapy has noticeably increased in the last years. At present, a successful realization of this interdisciplinary research is hampered by some unsolved problems. One of these problems this paper intended to clarify is how to find an estimate of the appropriate dosage of magnetic nanoparticles that injected into the tumor would help achieve an optimum temperature of 42°C, thus resulting in an increase of the susceptibility for apoptosis in tumor cells. We created a computational model in COMSOL: Multiphysics in order to analyze the heat dissipation within the tumor tissue. By considering various types of tissues with their respective physical and physiological properties (breast, liver, and skin tissues) and also by taking into account the amount of heat generated through the Brownian rotation and the Néel relaxation, it has been studied the tumor border temperature achieved for various concentrations of magnetic nanoparticles in their superparamagnetic behavior. Distinct simulations of a spherical tumor located in a cubical region of a volume of 1.2-3.5 cm3 within the tissue were designed. We performed a systematical variation of tumor diameter and particle dosage for every physical parameter of above mentioned tumor tissues (e.g., tissue density, tumor/tissue perfusion rate). By this systematization we intended to understand the interdependence of these parameters and their effects on hyperthermia therapy. [ABSTRACT FROM AUTHOR]

Metastases represent the final stage in cancer progression. Their early diagnosis and appropriate treatment are very important in order to maintain a high survival prognostic. The interest in MFH (Magnetic Fluid Hyperthermia) and cancer therapy has noticeably increased in the last years. There are still numerous problems that need to be solved before a clinical model may be tested. The goal of this paper is to both quantify the optimum dose of magnetic material and optimize injection sites in order to achieve a therapeutic temperature of 42°C that may induce apoptosis in tumor cells. A successful realization of this therapy implies a heating zone of at least 2 mm around the tumor. Finite Element Method (FEM) simulations of spherical metastases in liver and breast tissues near a blood vessel were performed using COMSOL Multiphysics (Heat Transfer Module) in order to simulate the temperature field produced by ferromagnetic nanoparticles within the tumor and healthy tissues. A systematical variation of tumor diameter and particle dosage was performed for every physical parameter for the tumor tissues mentioned above (e.g., tissue density, tumor/tissue perfusion rate) in order to understand the interdependence of these parameters and their effects on hyperthermia therapy. [ABSTRACT FROM AUTHOR]

At present, a successful realization of the magnetic fluid hyperthermia (MFH) therapy is conditioned by some unsolved problems. One of these problems is the choice of the correct particle concentration in order to achieve a defined temperature increase in the tumor tissue. A computer-based model was created using COMSOL: Multiphysics in order to simulate the heat dissipation within the tissue for typical configurations of the tumor position in relation to neighboring blood vessels as well as particle distribution within the tumor. The temperature achieved on the tumor border was investigated taking into account physiological parameters of different types of tissues. Using the correct nanoparticle dosage and considering their specific loss power, it is possible to estimate the efficiency of this therapeutic method. If the tumor shape and position are known by Suitable medical imaging techniques (e.g., MRI, CT), simulations like this one could provide data in order to achieve the optimum dose and particle distribution in the tumor. [ABSTRACT FROM AUTHOR]

In the present study, the optimal medium perfusion rate to be used for the continuous culture of a recombinant CHO cell line in a packed-bed bioreactor made of Fibra-Cel® disk carriers was determined. A first-generation process had originally been designed with a high perfusion rate, in order to rapidly produce material for pre-clinical and early clinical trials. It was originally operated with a perfusion of 2.6 vvd during production phase in order to supply the high cell density (2.5×107 cell ml−1 of packed-bed) with sufficient fresh medium. In order to improve the economics of this process, a reduction of the medium perfusion rate by −25% and −50% was investigated at small-scale. The best option was then implemented at pilot scale in order to further produce material for clinical trials with an improved second-generation process. With a −25% reduction of the perfusion rate, the volumetric productivity was maintained compared to the first-generation process, but a −30% loss of productivity was obtained when the medium perfusion rate was further reduced to −50% of its original level. The protein quality under reduced perfusion rate conditions was analyzed for purity, N-glycan sialylation level, abundance of dimers or aggregates, and showed that the quality of the final drug substance was comparable to that obtained in reference conditions. Finally, a reduction of −25% medium perfusion was implemented at pilot scale in the second-generation process, which enabled to maintain the same productivity and the same quality of the molecule, while reducing costs of media, material and manpower of the production process. For industrial applications, it is recommended to test whether and how far the perfusion rate can be decreased during the production phase – provided that the product is not sensitive to residence time – with the benefits of reduced cost of goods and to simplify manufacturing operations. [ABSTRACT FROM AUTHOR]

In anaesthetized rats a jejunal segment was perfused in situ varying the perfusion rate (0.1, 0.2, 0.5 ml/min) in a randomized order. The intraluminal radius of the segments was small (1.7 mm) or enlarged (3.1 mm) by increasing the intraluminal pressure. The appearance rate of butanol, antipyrine, salicylic acid, d-and l-phenylalanine but not of urea in the venous blood of the jejunal segments was increased up to 35 %, when the intraluminal perfusion rate was raised from 0.1 to 0.5 ml/min. Two factors contribute to this effect: the flattening of the concentration gradient down the segment and the reduction of the effective unstirred layer thickness. The length and the intraluminal radius of the perfused segments was not altered, when the perfusion rate was varied. Therefore, a change of the absorbing area did not contribute to the increase of the absorption rate induced by the increase of the perfusion rate. In the series with small intraluminal radius the experimental data corresponded to the theoretical predictions obtained for a laminar intraluminal flow. In the segments with enlarged intraluminal radius the increase of the absorption rate by raising the perfusion rate was less than expected for a laminar flow indicating that the flow might have been turbulent. The enlargement of the intraluminal radius from 1.7 to 3.1 mm increased the absorption rate up to 100%. [ABSTRACT FROM AUTHOR]