| 1. |
- Ahlstedt, Jonatan, et al.
(author)
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Evaluating vacquinol-1 in rats carrying glioblastoma models RG2 and NS1
- 2018
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In: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 9:9, s. 8391-8399
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Journal article (peer-reviewed)abstract
- Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor, and available experimental and routine therapies result in limited survival benefits. A vulnerability of GBM cells to catastrophic vacuolization and cell death, a process termed methuosis, induced by Vacquinol-1 (VQ-1) has been described earlier. In the present study, we investigate the efficacy of VQ-1 treatment in two syngeneic rat GBM models, RG2 and NS1. VQ-1 treatment affected growth of both RG2 and NS1 cells in vitro. Intracranially, significant reduction in RG2 tumor size was observed, although no effect was seen on overall survival. No survival advantage or effect on tumor size was seen in animals carrying the NS1 models compared to untreated controls. Furthermore, immunological staining of FOXP3, CD4 and CD8 showed no marked difference in immune cell infiltrate in tumor environment following treatment. Taken together, a survival advantage of VQ-1 treatment alone could not be demonstrated here, even though some effect upon tumor size was seen. Staining for immune cell markers did not indicate that VQ-1 either reduced or increased host anti-tumor immune response.
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| 2. |
- Van Hese, Jan, et al.
(author)
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Simulation of the Effect of Inhomogeneities in TEM Transmission Cells using the FDTD-Method
- 1992
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In: IEEE Transactions on Electromagnetic Compatibility. - : Institute of Electrical and Electronics Engineers (IEEE). - 0018-9375 .- 1558-187X. ; 34:3, s. 292-298
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Journal article (peer-reviewed)abstract
- The finite difference time domain (FDTD)-method is applied to model transverse electromagnetic (TEM) transmission cells in three dimensions. The perturbation of the TEM-mode and the standard field distribution in the TEM-cell, due to inhomogeneous materials placed inside the cell cavity, is evaluated. Particularly, the dependence of the disturbance of the TEM-mode on the dimensions of the material and its position in the TEM-cell is studied. Also the absorption of the electromagnetic fields in the lossy materials, placed in the cell, is calculated.
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| 3. |
- Ahlstedt, Jonatan, et al.
(author)
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Growth pattern of experimental glioblastoma
- 2020
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In: Histology and Histopathology. - 1699-5848. ; 35:8, s. 871-886
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Journal article (peer-reviewed)abstract
- Glioblastoma multiforme (GBM) is an aggressive primary brain malignancy with a very poor prognosis. Researchers employ animal models to develop potential therapies. It is important that these models have clinical relevance. This means that old models, propagated for decades in cultures, should be questioned. Parameters to be evaluated include whether animals are immune competent or not, the infiltrative growth pattern of the tumor, tumor volume resulting in symptoms and growth rate.We here describe the growth pattern of an experimental glioblastoma model in detail with GFP positive glioblastoma cells in fully immune competent animalsand study tumor growth rate and tumor mass as a function of time from inoculation.We were able to correlate findings made with classical immunohistochemistry and MR findings. The tumor growth rate was fitted by a Gompertz function. The model predicted the time until onset of symptoms for 5000 inoculated cells to 18.7±0.4 days, and the tumor mass at days 10 and 14, which are commonly used as the start of treatment in therapeutic studies, were 5.97±0.62 mg and 29.1±3.0 mg, respectively.We want to raise the question regarding the clinical relevance of the outline of glioblastoma experiments, where treatment is ofteninitiated at a very early stage. The approach presented here could potentially be modified to gain information also from other tumor models.
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| 4. |
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| 5. |
- Eberhardt, Jacob, et al.
(author)
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Blood-brain barrier permeability and nerve cell damage in rat brain 14 and 28 days after exposure to microwaves from GSM mobile phones.
- 2008
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In: Electromagnetic Biology and Medicine. - : Informa UK Limited. - 1536-8386 .- 1536-8378. ; 27:3, s. 215-229
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Journal article (peer-reviewed)abstract
- We investigated the effects of global system for mobile communication (GSM) microwave exposure on the permeability of the blood-brain barrier and signs of neuronal damage in rats using a real GSM programmable mobile phone in the 900 MHz band. Ninety-six non-anaesthetized rats were either exposed to microwaves or sham exposed in TEM-cells for 2 h at specific absorption rates of average whole-body Specific Absorption Rates (SAR) of 0.12, 1.2, 12, or 120 mW/kg. The rats were sacrificed after a recovery time of either 14 or 28 d, following exposure and the extravazation of albumin, its uptake into neurons, and occurrence of damaged neurons was assessed. Albumin extravazation and also its uptake into neurons was seen to be enhanced after 14 d (Kruskal Wallis test: p = 0.02 and 0.002, respectively), but not after a 28 d recovery period. The occurrence of dark neurons in the rat brains, on the other hand, was enhanced later, after 28 d (p = 0.02). Furthermore, in the 28-d brain samples, neuronal albumin uptake was significantly correlated to occurrence of damaged neurons (Spearman r = 0.41; p < 0.01).
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| 6. |
- Engström, Per E., et al.
(author)
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Effect of high voltage electrical pulses on subcutaneous glioma tumours on rats
- 1998
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In: Bioelectrochemistry and Bioenergetics. - 0302-4598. ; 47:1, s. 163-166
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Journal article (peer-reviewed)abstract
- The antitumour effect of applied high voltage exponential pulses was investigated on rats with subcutaneously implanted N32 brain tumours. Superficial tumours on the thigh were produced by the injection of 100 000 N32 glioma cells on Fischer-344 rats. Four weeks after inoculation, a solid tumour has grown to a size of about 1 cm located directly under the skin. Short electric high voltage pulses were given transdermally through stainless steel plate electrodes. Sixteen exponential pulses with initial field strength of 1300-1400 V/cm and a time constant of 1 ms were delivered with a BTX600 device at approximately one pulse per second. The treatment was repeated during 4 consecutive days. Tumour response was studied by measuring the length, width and thickness of the tumour with a slide-calliper and estimating the tumour volume as an ellipsoid. Animals (treated and controls) were sacrificed when the size of the tumour had reached a predetermined value (5 cm3). In the first experiment this occurred after 50±4 days for the treated animals, excluding cured, compared to 40±1.3 for their controls and in the second experiment after 64±24 days excluding cured animals compared to 37.6±3 for the controls. All treated animals showed an initial partial or complete tumour remission within a few days after the end of the 4-day treatment. Two out of ten treated animals were cured with no sign of recurrence after 100 days. Copyright (C) 1998 Elsevier Science S.A.
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| 7. |
- Förnvik, Karolina, et al.
(author)
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Anti-C1-inactivator treatment of glioblastoma
- 2018
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In: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 9:100, s. 37421-37428
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Journal article (peer-reviewed)abstract
- Purpose: Glioblastoma multiforme (GBM) or astrocytoma grade IV is the most common type of primary brain tumor in adults. In the present study, we investigate the role of the complement system in the glioblastoma situation in an experimental model, since we have previously been able to show a blockade of this system in the glioblastoma setting. Technique and results: A GFP-positive glioblastoma cell line was used to induce glioblastomas subcutaneously in rats (n=42). Antibodies against C1-Inactivator (C1-IA) were used to try to re-activate the complement system. We were able to demonstrate an increased survival in rats treated with anti-C1-IA with an intratumoral route, and we could establish the same the results in a second series. Serum analyses revealed decreased levels of IL-1b and GM-CSF in animals 24 days after tumor cell inoculation in the anti-C1-IA group when compared to controls. Immunohistochemistry revealed decreased expression of C1-IA following treatment. Interpretation: These results are in line with our previous work showing an upregulation of C1-IA, which is able to block the classical complement pathway, in glioblastomas. Treatment with antibodies against C1-IA seems to be beneficial in the glioblastoma situation, and no side effects could be seen in our experiments.
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| 8. |
- Förnvik, Karolina, et al.
(author)
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C1-inactivator is upregulated in glioblastoma
- 2017
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:9
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Journal article (peer-reviewed)abstract
- Background: Glioblastoma is the most common and aggressive type of primary brain tumor in adults. A key problem is the capacity of glioma cells to inactivate the body’s immune response. The complement system acts as a functional bridge between the innate and adaptive immune response. Still, the role of the complement system has almost been forgotten in glioma research. In our present study, we hypothesize that C1 inactivator (C1-IA) is upregulated in astrocytoma grade IV, and that its inhibition of the complement system has beneficial effects upon survival. Methods and results: We have explored this hypothesis both on gene and protein levels and found an upregulation of C1-IA in human glioblastoma cells using data from a publicly available database and our own mRNA material from glioblastoma patients. Furthermore, we demonstrated the presence of C1-IA by using immunohistochemistry on glioma cells from both humans and rats in vitro. Finally, we could demonstrate a significantly increased survival in vivo in animals inoculated intracerebrally with glioma cells pre-coated with C1-IA antibodies as compared to control animals. Conclusions: Our findings indicate that overexpression of C1-IA is present in glioblastomas. This could be demonstrated both at the gene level from patients with glioblastoma, on mRNA level and with immunohistochemistry. Treatment with antibodies against C1-IA had beneficial effects on survival when tested in vivo.
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| 9. |
- Förnvik, Karolina, et al.
(author)
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ITPP treatment of RG2 glioblastoma in a rat model
- 2016
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In: Anticancer research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 36:11, s. 5751-5755
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Journal article (peer-reviewed)abstract
- Background: Inositol trispyrophosphate (ITPP) has been shown to reduce tumour growth in different animal cancer models, as well as of human U87 glioma cells grafted onto chick chorioallantoic membrane (CAM). The aim of this study was to establish whether ITPP crosses the blood-brain barrier and whether it halts the growth of RG2 glioblastoma tumour. Materials and Methods: A model comprising of Fischer 344 rats was chosen and RG2 cells were implanted either intracranially, or subcutaneously on the left hind leg, and the animals were treated with ITPP either intraperitoneally, intravenously or both routes combined. Overall survival was then calculated. Results: No prolonged survival was seen in animals treated with ITPP. The route of ITPP administration did not affect outcome. Conclusion: ITPP had no favourable effect upon survival in our animal model with RG2 glioblastoma tumours in Fischer 344 rats.
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| 10. |
- Förnvik, Karolina, et al.
(author)
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What is the role of CRP in glioblastoma?
- 2021
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In: Cancer Treatment and Research Communications. - : Elsevier BV. - 2468-2942. ; 26
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Journal article (peer-reviewed)abstract
- Background: Glioblastoma is the most common primary malignant brain tumor in adults. Previous studies have suggested that CRP (C-reactive protein) could serve as a biomarker candidate as well as a prognostic factor in glioblastoma patients, and we here further investigate its potential role. Materials and methods: Publicly available datasets were used to compare gene expression between brain samples from glioblastoma patients and non-tumor tissue. The structure of CRP was compared between humans and rats. Glioblastoma cells from humans and rats were stained with anti-CRP. Fischer 344 rats were inoculated with syngeneic glioblastoma cells pre-coated with anti-CRP, and survival was monitored. CRP concentration in rats carrying glioblastoma was followed. Results: CRP was upregulated on one locus on gene level in glioblastoma tissue as compared to non-tumor brain tissue, but not in glioma stem cells as compared to neural stem cells. The structure of the CRP protein was a characteristic pentamer in both humans and rats. Both human and rat glioblastoma cells were clearly positive for anti-CRP staining. Pre-coating of glioblastoma cells with anti-CRP antibodies did not affect survival in rats with intracranial tumors. Serum levels of CRP increased during tumor progression but did not reach significantly different levels. Conclusions: Both human and rat glioblastoma cells could be stained with anti-CRP antibodies in vitro. In a syngeneic glioblastoma rat model we could see an increase in serum CRP during tumor progression, but coating glioblastoma cells with anti-CRP antibodies did not provide any survival change for the animals.
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