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- Ahlstedt, Jonatan, et al.
(författare)
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Growth pattern of experimental glioblastoma
- 2020
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Ingår i: Histology and Histopathology. - 1699-5848. ; 35:8, s. 871-886
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Tidskriftsartikel (refereegranskat)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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| 2. |
- Björkman-Burtscher, Isabella, et al.
(författare)
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Proton MR spectroscopy and preoperative diagnostic accuracy: an evaluation of intracranial mass lesions characterized by stereotactic biopsy findings
- 2000
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Ingår i: AJNR. - 1936-959X. ; 21:1, s. 84-93
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: MR imaging has made it easier to distinguish among the different types of intracranial mass lesions. Nevertheless, it is sometimes impossible to base a diagnosis solely on clinical and neuroradiologic findings, and, in these cases, biopsy must be performed. The purpose of this study was to evaluate the hypothesis that proton MR spectroscopy is able to improve preoperative diagnostic accuracy in cases of intracranial tumors and may therefore obviate stereotactic biopsy. METHODS: Twenty-six patients with intracranial tumors underwent MR imaging, proton MR spectroscopy, and stereotactic biopsy. MR spectroscopic findings were evaluated for the distribution pattern of pathologic spectra (NAA/Cho ratio < 1) across the lesion and neighboring tissue, for signal ratios in different tumor types, and for their potential to improve preoperative diagnostic accuracy. RESULTS: Gliomas and lymphomas showed pathologic spectra outside the area of contrast enhancement while four nonastrocytic circumscribed tumors (meningioma, pineocytoma, metastasis, and germinoma) showed no pathologic spectra outside the region of enhancement. No significant correlation was found between different tumor types and signal ratios. MR spectroscopy improved diagnostic accuracy by differentiating infiltrative from circumscribed tumors; however, diagnostic accuracy was not improved in terms of differentiating the types of infiltrative or circumscribed lesions. CONCLUSION: MR spectroscopy can improve diagnostic accuracy by differentiating circumscribed brain lesions from histologically infiltrating processes, which may be difficult or impossible solely on the basis of clinical or neuroradiologic findings.
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| 6. |
- Nittby, Henrietta, et al.
(författare)
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Zebularine induces long-term survival of pancreatic islet allotransplants in streptozotocin treated diabetic rats.
- 2013
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:8
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Tidskriftsartikel (refereegranskat)abstract
- Coping with the immune rejection of allotransplants or autologous cells in patients with an active sensitization towards their autoantigens and autoimmunity presently necessitates life-long immune suppressive therapy acting on the immune system as a whole, which makes the patients vulnerable to infections and increases their risk of developing cancer. New technologies to induce antigen selective long-lasting immunosuppression or immune tolerance are therefore much needed.
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| 13. |
- Salford, Leif, et al.
(författare)
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Search for effective therapy against glioblastoma multiforme - Clinical immunisation with autologous glioma cells transduced with the human interferon-gamma gene
- 2002
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Ingår i: Developments in Neuroscience. Proceedings of the 2nd International Mt Bandai Symposium for Neuroscience 2001. - 0531-5131. ; 1247, s. 211-220
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Konferensbidrag (refereegranskat)abstract
- Based upon earlier experimental work by our group, we have started a human immuno-gene therapy study. The goal is to study the effects of immunisation with autologous tumour cells expressing gene sequences for human interferon-gamma For more than two decades we have sought for efficient treatment against malignant gliomas. Our most successful treatment in the animal models is immuno-gene therapy where murine genes for the cytokines IFN-gamma, IL-7 and B7-1 were chosen for their ability to stimulate different stages of the pathway for cytotoxic T lymphocyte (CTL) activation. Rats of the syngeneic inbred strain Fischer 344 had rat glioma cells of the N32 line inoculated in the right caudate nucleus, and 1 or 3 days later N32 cells transfected with either IFN-gamma, IL-7 or B7-1 genes were injected subcutaneously (and in some studies intraperitoneally). This treatment was repeated three to four times with 7- to 14-day interval and resulted in significantly improved survival compared with treatment with wild-type rat glioma cells (e.g. not transfected with the cytokine genes). The continued work concentrated on treatment with IFN-gamma secreting tumour cells of both the N32 line and also a newly developed ENU-induced rat glioma cell line called N29. This work proved the effectiveness of the technique. Cure was achieved in 72% of the animals treated with the IFN-gamma cells. Tumour-infiltrating leukocytes from N32-IFN-gamma-immunised animals showed a significantly stronger infiltration by CD8+ T-cells, significantly more NK cells, and an increased number of CD25-expressing T-cells. These results confirmed the possible usefulness of IFN-gamma-transfected tumour cells in the immune-therapy of rat brain tumours. The animal experiments have motivated us to start a human immuno-gene therapy study including 20 patients with glioblastoma multiforme (GBM), where >80% of the tumour can be surgically removed. The goal is to ascertain whether immunisation with autologous tumour cells expressing gene sequences for human interferon-gamma is safe for the patients, gives rise to an immunological response, and adds any beneficial effect to conventional therapy (tumour growth, prolonged survival). Hitherto, nine patients have been included in the study, two of which have received 6 and 10 immunisations, respectively. Two patients have died from their disease before cells have been ready for immunisation; in two cases no malignant cells have appeared in the cell cultures and three patients are ready to start their immunisation shortly. The immunisation takes place in the dermis of the upper arm. Seven days after each immunisation, a skin biopsy is taken from the centre of one of the injection sites. The composition of the cellular infiltration in the skin is studied by markers for T lymphocytes (CD3); helper cells, subset of T cells (CD4); killer cells, subset of T cells (CD8); natural killer cells (CD16) and B lymphocytes, B cells (CD20). Also the expression of cytokines for functional T cell subsets are studied: IL-2, IL-4, IL-10, IL-12, IL-18, TNF-alpha and IF-gamma and TGF-beta(1,2 and 3-) Peripheral blood is sampled both before and after operation and also after each immunisation event. Co-culture of this blood with tumour cells from the patient allows for a selection of T-cells that can recognise tumour-specific antigens. The results from the first human treatments are presented. (C) 2002 Published by Elsevier Science B.V.
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| 15. |
- Suzuki, Norihiro, et al.
(författare)
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Central origins of preganglionic fibers to the sphenopalatine ganglion in the rat. A fluorescent retrograde tracer study with special reference to its relation to central catecholaminergic systems
- 1990
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Ingår i: Journal of the Autonomic Nervous System. - : Elsevier BV. - 0165-1838. ; 30:2, s. 101-109
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Tidskriftsartikel (refereegranskat)abstract
- The brainstem origin of preganglionic fibers to the sphenopalatine ganglion in rat was revealed by the aid of the retrograde axonal tracer True Blue (which does not traverse to a second order neuron) applied deep in the sphenopalatine ganglion or the Vidian nerve on one side. The majority of fibers originate in the ipsilateral lacrimo-muconasal nucleus in the ventrolateral rostral medulla oblongata and caudal pons. A smaller number of fibers originate more dorsomedially and caudally in the medullary reticular formation. After application to the ganglion a third small group of labelled neurons was found more rostrally in the brainstem, in the reticular formation ventrolateral to the caudal part of the dorsal raphe nucleus. Simultaneous visualization of catecholaminergic nerves revealed that the labelled neurons in the lacrimo-muconasal nucleus were heavily innervated by catecholaminergic fibers. It appears from previous studies that the preganglionic neurons may not be cholinergic. None of the labelled neurons in the brainstem stained positively for catecholamines. Thus, further studies are required to elucidate the transmitter(s) used in these neurons.
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| 16. |
- van Westen, Danielle, et al.
(författare)
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Functional magnetic resonance imaging at 3T as a clinical tool in patients with intracranial tumors.
- 2005
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Ingår i: Acta Radiologica. - : SAGE Publications. - 1600-0455 .- 0284-1851. ; 46:6, s. 599-609
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To investigate the potential of functional magnetic resonance imaging (fMRI) at 3T as a clinical tool in the preoperative evaluation of patients with intracranial tumors. High magnetic field strength such as 3T is of benefit for fMRI because signal-to-noise ratio and sensitivity to susceptibility changes are field-strength-dependent. Material and Methods: Twenty patients with tumors close to eloquent sensorimotor or language areas were studied. Motor, sensory, and two language paradigms (word generation, rhyming) were used; their effectiveness was determined as the percentage of patients in whom the functional area of interest was activated. Activation maps were calculated and their quality rated as high, adequate, or insufficient. The influence of fMRI on the neurosurgical decision regarding operability, surgical approach, and extent of the resection, was assessed. Results: Paradigm effectiveness was 90% for motor and 95% for sensory stimulation, and varied from 79% to 95% for word generation and rhyming in combination. Ninety percent of the activation maps held high or adequate quality. fMRI proved useful: in the decision to operate (9 patients), in the surgical approach (13 patients), and in extent of the resection (12 patients). Conclusion: fMRI at 3T is a clinically applicable tool in the work-up of patients with intracranial tumors.
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