Дисертації з теми "Glioma tumors"
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Konnully, Augustus Meera Bessy. "Characterization of cellular heterogeneity in Diffuse Low Grade Glioma." Thesis, Montpellier, 2020. http://www.theses.fr/2020MONTT038.
Повний текст джерелаDiffuse Low-Grade Gliomas (DLGG) are WHO grade II glial tumors affecting younger adults. They are characterized as silent, slow growing tumors with fewer mitotic activities. However, they diffuse and invade the healthy brain via blood vessels and nerve fibers. These, over a period of years develop to malignant Glioblastoma, aggressive brain tumors where patients have an average medial survival of 12-15 months after diagnosis. Ill-defined phenotypic and cellular diversity of DLGG poses serious limitation to treatment and prevention at the early stage.In my PhD thesis, I aimed to address this limitation by characterizing the cellular heterogeneity in IDH1-mutated DLGG. By performing immunofluorescence analysis on grade II astrocytoma and oligodendroglioma, I have identified two largely non-overlapping cellular subpopulations expressing SOX9 and OLIG1 transcription factors, which represent astrocyte-like and oligodendrocyte-like cells, respectively. Upon further investigation, I have shown that these subpopulations express distinct molecular markers. Sox9 cells are associated with APOE, KCNN3, CRYAB and ID4, while Olig1 cells showed strong correlation with the expression of PDGFRA, SOX8, MASH1, and SOX4. In addition, the sox9 cells show a particular activation of signaling pathways including Notch, BMP and their downstream targets.To ascertain the role of Notch signaling in regulating the formation of these tumoral subpopulations, I used magnetic sorting of tumor cells from freshly resected glioma samples and overexpressed Notch Intracellular Domain (NICD), an active form of Notch. Increased Notch activation resulted in an upregulation of Sox9- and downregulation of Olig1-associated cell markers. I have then extended these analyses on one anaplastic IDH1 mutated patient derived cell line which reproduced similar gene expression profile confirming the robustness of the role of Notch signaling in regulating the plasticity of the cells. Parallel experiments performed by activation of Bone Morphogenetic Protein (BMP) signaling on IDH1 mutated cell line did not show a prominent effect on the plasticity. Nevertheless, BMP signal activation highly upregulated CRYAB, a SOX9 related marker and downregulated OLIG1 and OLIG2.In conclusion, I have identified two non-overlapping tumor subpopulations in diffuse low-grade gliomas and demonstrated the deterministic role of Notch signaling pathway in their formation. I believe that these findings would aid in better understanding tumoral heterogeneity in DLGG and be extended in designing new therapeutic strategies against these tumors
Safdar, Shahana. "Peptide-targeted nitric oxide delivery for the treatment of glioblatoma multiforme." Diss., Georgia Institute of Technology, 2012. http://hdl.handle.net/1853/45797.
Повний текст джерелаMunson, Jennifer Megan. "Novel nanocarriers for invasive glioma." Diss., Georgia Institute of Technology, 2011. http://hdl.handle.net/1853/41226.
Повний текст джерелаDan, Michael. "Human anti-glioma monoclonal antibodies from patients with neurological tumors." Thesis, McGill University, 1989. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=74367.
Повний текст джерелаMurren, Robert John. "Intracytoplasmic lipid droplets in high grade glioma : metabolism and target for therapy." Thesis, University of Birmingham, 2018. http://etheses.bham.ac.uk//id/eprint/8134/.
Повний текст джерелаMörén, Lina. "Metabolomics and proteomics studies of brain tumors : a chemometric bioinformatics approach." Doctoral thesis, Umeå universitet, Kemiska institutionen, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-111309.
Повний текст джерелаMcNeeley, Kathleen Margaret. "Modulating liposomal stealth properties to evade RES and target tumors." Diss., Atlanta, Ga. : Georgia Institute of Technology, 2008. http://hdl.handle.net/1853/26650.
Повний текст джерелаCommittee Chair: Ravi V. Bellamkonda; Committee Member: Ananth V. Annapragada; Committee Member: Andrew Lyon; Committee Member: Gang Bao; Committee Member: Niren Murthy. Part of the SMARTech Electronic Thesis and Dissertation Collection.
Ghasimi, Soma. "Genotype-phenotype studies in brain tumors." Doctoral thesis, Umeå universitet, Onkologi, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-83185.
Повний текст джерелаCancer research foundation in northern Sweden and Lions cancer research foundation at Umeå university
Uyar, Ramazan [Verfasser], and Rainer [Akademischer Betreuer] Glaß. "Glioma-associated mesenchymal stem cells have profound effects on brain tumors / Ramazan Uyar ; Betreuer: Rainer Glaß." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2019. http://d-nb.info/1202011683/34.
Повний текст джерелаKao, Chen-Yu. "Developing a Minimally Invasive Sustained Release System for Glioma Therapy." Thesis, Georgia Institute of Technology, 2007. http://hdl.handle.net/1853/19757.
Повний текст джерелаQuintero, Bernabeu Maria Rosa. "Estudi de la significació cel·lular dels "lípids mòbils" visibles per RMN en cèl·lules C6 de glioma de rata." Doctoral thesis, Universitat Autònoma de Barcelona, 2007. http://hdl.handle.net/10803/3563.
Повний текст джерелаEls senyals de lípids visibles per RMN (ML) de les cèl·lules C6 han estat monitorats a 9,4 i 11,7 T (pols i adquisició i 136 ms temps d'eco) en sediments cel·lulars per espectroscòpia de 1H NMR. S'ha trobat un comportament reproduïble amb el creixement. Els ML augmenten de fase log (dia 4 de cultiu) a fase postconfluent (dia 7 de cultiu). Aquest comportament es correspon amb el percentatge de cèl·lules que contenent gotícules citosòliques detectables per tinció amb Nile Red i epifluorescència. (rang 23% -60% de cèl·lules). El nombre de cèl·lules positives augmenta després de la sembra (dia 0-1), disminueix a fase log (dia 2-4), augmenta altre cop amb la confluència (dia 5) i encara més en post-confluència (dia 7). L'aturada de la proliferació induïda per deprivació de factors de creixement indueix una major acumulació de gotícules citosòliques (fins a 100%) i un major augment en els ML ( fins a 21 vegades respecte de les cèl·lules de fase log de dia 4 de cultiu).
La quantificació del lípids neutres en extractes lipídics totals de cèl·lules C6 per cromatografia en capa prima (TLC) mostra que no hi ha canvis significatius amb el creixement o l'aturada de proliferació en els principals tipus de lípids neutres presents (triacilglicerols, TAG; diacilglicerols, DAG; esters de colesterol, ChoEst) excepte pels DAG, els quals decreixen en cèl·lules de dia 7.
La quantificació per 1H-13C HMQC dels extractes de cèl·lules C6 (cèls. dia 4, fase log, n=3; i dia 7, post-confluenst, n=3) i and {1}-13C-glucosa enriquida 99% (cèls. dia 4, , n=3, incubació 2h4; i dia 7, n=3, incubació 48h) va mostrar que no hi havia diferències significatives en el contingut de TEG entre cèl·lules de dia 4 i de dia 7. La distribució del marcatge obtinguda suggereix una compartimentalització de la síntesi de PL i TAG a partir de DAG, i un origen diferent de glucosa per la síntesi de TAG en les condicions experimentals.
L' aparent discrepància entre els resultants d'RMN, microscòpia òptica I TLC pot ser explicada si es tenen en compte canvis biofísics en el pool de lípids neutres i els resultants de marcatge. Es proporciona una explicació cel·lular pels resultats obtinguts: la hipòtesi de la llançadora de TAG.
NMR-visible mobile lipids (ML) resonances at 1.28 and 0.9ppm have been described in the spectral pattern of aggressive tumours and in cultured cell types. These ML mostly originate from triacylglicerol (TAG) in droplets (1-10 micrometers of diameter) and have been related to necrosis and hypoxia in tumours and proliferation rate in cultured cells. Proper understanding of the biochemical and biophysical origin of these ML could help MRS of human brain tumours to provide useful information for diagnosis, prognosis and therapy planning.
NMR-visible mobile lipid (ML) signals of C6 glioma cells have been monitored at 9.4 and 11.7 T (single pulse and 136 ms echo time) from cell pellets by 1H NMR spectroscopy. A reproducible behavior with growth has been found. ML signals increase from log phase (4 day of culture) to postconfluence (7 day of culture). This ML behavior is paralleled by the percentage of cells containing epifluorescence detectable Nile Red stained cytosolic droplets (range 23% - 60% of cells). The number of positive cells increases after seeding (day 0-1), decreases at log phase (day 2-4), increases again at confluence (day 5) and even further at post-confluence (day 7). C6 cells proliferation arrest induced by growth factors deprivation induces an even higher accumulation of cytosolic droplets (up to 100% of cells) and a large ML increase (up to 21 -fold with respect to 4 day log phase cells)
When neutral lipid content is quantified by thin-layer chromatography (TLC) on total lipid extracts of C6 cells, no statistically significant change can be detected with growth or growth arrest in major neutral lipid containing species (triacylglycerol, TAG, diacylglycerol, DAG, cholesterol esters, ChoEst) except for DAG, which decreased in post-confluent, 7 day cells.
Quantitation of C6 lipid extracts of cultured cells (day 4 cells, log phase, n=3, and day 7 cells, postconfluent, n=3) and {1}-13C-glucose 99% enriched grown cells (day 4 cells, n=3, 24h incubation with 13C enriched glucose, day 3-day 4, and day 7 cells,n=3, 48h incubation with 13C enriched glucose, day 5-day 7) by 1H-13C HMQC showed no statistically significant changes in TAG content between day 4 and day 7 cultured cells. The labelling distribution obtained suggests a cellular compartimentalization of the synthesis pathway for PL and TAG from DAG, and an origin different from glucose for TAG synthesis under the experimental conditions (log phase and post-confluence).
The apparent discrepancy between NMR, optical microscopy and TLC results can be reconciled if possible biophysical changes in the neutral lipid pool with growth and labeling results are taken into account. A cellular explanation for the observed results is proposed: the TAG-droplet-size-change hypothesis.
Sakata, Akihiko. "Grading glial tumors with amide proton transfer MR imaging: different analytical approaches." Kyoto University, 2016. http://hdl.handle.net/2433/215431.
Повний текст джерелаKyoto University (京都大学)
0048
新制・課程博士
博士(医学)
甲第19605号
医博第4112号
新制||医||1014(附属図書館)
32641
京都大学大学院医学研究科医学専攻
(主査)教授 村井 俊哉, 教授 平岡 眞寛, 教授 山田 泰広
学位規則第4条第1項該当
Roller, Benjamin Thomas. "A nanoencapsulated visible dye for intraoperative delineation of brain tumor margins." Thesis, Georgia Institute of Technology, 2011. http://hdl.handle.net/1853/42805.
Повний текст джерелаSuwala, Abigail Kora [Verfasser]. "Targeted glioma stem cell depletion through pharmacological WNT inhibition as a novel therapy for malignant brain tumors / Abigail Kora Suwala." Düsseldorf : Universitäts- und Landesbibliothek der Heinrich-Heine-Universität Düsseldorf, 2019. http://d-nb.info/1190884062/34.
Повний текст джерелаLanser, Brittany. "Characterization of checkpoint adaptation in human fibroblastic glioma cells and an analysis of protein phosphatase inhibitors." Thesis, Lethbridge, Alta. : University of Lethbridge, Dept. of Biological Sciences, c2012, 2012. http://hdl.handle.net/10133/3390.
Повний текст джерелаxi, 114 leaves : ill. (some col.) ; 29 cm
Fernández, Flores Francisco. "The cancer stem cell hypothesis in spontaneous canine gliomas: from tumors to neurogenesis in the adult dog." Doctoral thesis, Universitat Autònoma de Barcelona, 2016. http://hdl.handle.net/10803/400385.
Повний текст джерелаCancer stem cells (CSCs) can originate both from the transformation of normal stem cells as progenitors or from more differentiated cells that have acquired capacity for self-renewal. The hypothesis of the CSCs proposes that a specific subpopulation of cancer stem cells is responsible for maintaining the tumor. This hypothesis has been demonstrated in a wide variety of tumors, including gliomas. Nestin and CD133 are used as markers for the detection and study of neural stem cells. In the present study, a total of 20 canine brain tumors were diagnosed as glioma, according to the international classification of tumors of the central nervous system in humans. They were studied by immunohistochemistry (IHC) using Nestin and CD133 as markers of neural precursors; Neu-N, doublecortin (DCx) and βIII tubulin as neuronal markers; glial fibrillary acidic protein (GFAP), vimentin, S-100 protein and protein Olig2 as glial markers and Ki67 as a marker for cell proliferation. These tumors were neuropathologically classified as: oligodendogliomas (Grade II), anaplastic oligodendrogliomas (Grade III), mixed glioma (grade II) and glioblastomas (grade IV). IHC evaluation showed higher positivity for Nestin and CD133 in high-grade gliomas (HGG). Olig2 was expressed in most tumors, whereas positivity for GFAP was higher in the mixed glioma and glioblastomas. Differentiated neuron markers were negative, while in some HGGs DCX positivity was detected. Our results are in agreement with the CSCs hypothesis, confirming the presence of undifferentiated neural precursors in canine gliomas. Subsequently, tissue grafts extracted from areas of the center and periphery of canine gliomas were cultured in vitro by neurosphere assay in order to assess the ability of proliferation, expansion and survival of the neural progenitors. Neurospheres of all samples corresponding to the center of the tumor were obtained indicating the existence of neural precursors in tumors of all grades of canine glioma. Furthermore, the amount of cells capable of proliferating was increased in HGGs, indicating the possible influence of these neural precursors in their malignant behavior. The neural precursors isolated from all samples were able to differentiate into three neural lines indicating their multipotentiality. These results demonstrated the involvement of neural progenitors in canine gliomas, according to the second criteria for demonstration of the hypothesis of CSCs. In parallel neural stem cells from normal postnatal adult dog brain phases were studied. The cytoarchytecture of its main niche it was studied in the adult brain. This corresponds to the subventricular zone (SVZ) which has been widely described in human and murine species. By histological, immunohistochemical, ultrastructural and cell culture studies, the presence of multipotent neural cells in SVZ was confirmed, residing in neurogenic niches and structurally and cellularlly similar to those described in other mammalian species. Moreover, the architecture of these components was similar to that described in humans, probably related with complexity similar brain structures, which could be related to adult neurogenesis related processes. Finally, chains of migratory neuroblasts associated with vascular structures outside the SVZ indicated a high migration capability and adaptability of resident neural stem cells in the brain of adult and comparable with similar events described in other mammalian species including humans. The results of the studies performed in this thesis conclude that the dog can be a relevant animal model in future related to the identification of new therapeutic targets in the field of comparative oncology studies, as well as a model to consider in studies and the progress of studies related to neurogenesis in the adult individual.
Bielecki, Peter. "Advanced Mesoporous Silica Nanoparticles for the Treatment of Brain Tumors." Case Western Reserve University School of Graduate Studies / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=case159558503832021.
Повний текст джерелаMirbahai, Ladan. "Biomarkers of cell stress and cell death detected by proton high resolution magic angle spinning (¹H HR-MAS) nuclear magnetic resonance (NMR) spectroscopy in a rat glioma cell line." Thesis, University of Birmingham, 2010. http://etheses.bham.ac.uk//id/eprint/619/.
Повний текст джерелаBeccaria, Kévin. "Evaluation de la diffusion intracérébrale des drogues antinéoplasiques après ouverture de la barrière hémato-encéphalique induite par ultrasons : Application aux gliomes malins de l’enfant Brainstem Blood-Brain Barrier Disruption and Enhanced Drug Delivery with an Unfocused Ultrasound Device – A Preclinical Study in Healthy and Tumor-Bearing Mice Ultrasound-Induced Blood-Brain Barrier Disruption for the Treatment of Gliomas and other Primary CNS Tumors Blood-Brain Barrier Disruption with Low-Intensity Pulsed Ultrasound for the Treatment of Pediatric Brain Tumors: A Review and Perspectives." Thesis, université Paris-Saclay, 2020. http://www.theses.fr/2020UPASS044.
Повний текст джерелаHigh-grade gliomas represent about 15% of pediatric brain tumors. No progress has been made in the treatment of these tumors during the last decades, and their prognosis remains dismal. The blood-brain barrier (BBB) plays a major role in the failure of medical treatments since it prevents most molecules to reach the brain, thus limiting the delivery of antineoplastic drugs to brain tumors. Disruption of the BBB (BBBD) with low intensity pulsed ultrasound in association with intravenous microbubbles is a technique that allows for safe, transient, and localized opening of the BBB. In this thesis, we confirmed the capacity of a new microbubble contrast agent to induce BBBD with ultrasound. We showed that opening of the BBB in the brainstem is possible with a nonfocused ultrasound device (SonoCloud®), in both healthy mice and a murine model of DIPG. We were able to increase irinotecan and panobinostat delivery in the brainstem of both healthy and tumor-bearing mice after BBBD, but we did not observe increased in overall survival. Preliminary studies have also been performed with checkpoints inhibitors and natural killer cells in a murine model of supra-tentorial high-grade glioma, but we were not able to increase survival in these models anymore. Finally, we prepared the first clinical trial that will evaluate the feasibility and tolerance of ultrasound-induced BBBD with the SonoCloud® device in the pediatric population. This trial will begin during the first semester of 2020
Grieger, Wolfgünter Helwig. "Differenzierung von Hirntumoren mittels dynamischer Magnetresonanztomographie." Doctoral thesis, Humboldt-Universität zu Berlin, Medizinische Fakultät - Universitätsklinikum Charité, 2005. http://dx.doi.org/10.18452/15344.
Повний текст джерелаA method of dynamic magnet resonance imaging (dMRI) was used, which allowed for the first time to determine simultaneously several parameters in patients with brain tumors. These parameters were the regional cerebral blood volume (rCBV), the regional cerebral blood flow, and in addition, permeabilities, interstitial volumes, and the cell volume. First, it should be determined to what extent these parameters allow a better classification of the malignancy of brain tumors. Second, it should be evaluated how far it is possible to differentiate the examined tumor groups from each other. Third, a method for an in-vivo-grading specifically for gliomas should be developed. Altogether 60 patients with different tumors such as gliomas, metastasis, meningiomas, and lymphomas were examined. The data of the dMRI examination were evaluated using a pharmacokinetic model. For every patient, the parameters mentioned above were shown in maps and calculated quantitatively. The mean rCBV resulted in the best tumor differentiation: within the group of gliomas it was possible to differentiate significantly between grade-II- and grade-III-gliomas and grade-II- and grade-IV-gliomas. Furthermore, meningiomas were differentiated significantly from the other tumors. In respect to the group of gliomas, the tumor grades determined by the developed in-vivo-grading corresponded with the WHO grade of each glioma in 71 % of the cases. The parameter maps were not only usefull for tumor differentiation, but also yielded information concerning the heterogenous tumor structure. Additionally, these maps allowed to differentiate scar tissue from tumor tissue and effects of a radiotherapy could be observed. Finally, information about the vessel architecture and the growth of different tumor groups could be obtained. The parameters determined by the dMRI method used here offered several advantages: it was possible to differentiate between single tumor groups. For the gliomas, a quantitative malignancy classification resulted from the in-vivo-grading. The information concerning the structure of the heterogeneity of the tumor allows for better biopsy results. Additionally, information was also obtained concerning the pathophysiology of the tumors and it seemed possible to observe changes after a therapy.
Swanson, Kristin Rae. "Mathematical modeling of the growth and control of tumors /." Thesis, Connect to this title online; UW restricted, 1999. http://hdl.handle.net/1773/6764.
Повний текст джерелаPadovani, Laëtitia. "Caractérisation moléculaire des tumeurs cérébrales circonscrites de l'enfant." Thesis, Aix-Marseille, 2013. http://www.theses.fr/2013AIXM5018.
Повний текст джерелаThe OMS classification for pediatric brain tumors includes glial tumors and mixed glial and glioneuronal tumors, diffuse and no diffuse glioma. All strategic decision making are based on this current classification but it drives to some limits of diagnosis reproductibility.The goal of our study was to define molecular profils for low grade no diffuse pediatric brain tumors including pilocytic astrocytoma (PA), dysembryoplasic neuroepithelial tumor (DNT), pleiomorphic xanthoastrocytoma (PXA) and benign gangliogliome (GG), to improve the quality of diagnosis, define different subgroups with different prognosis and then to improve treatment strategy decision making.No molecular difference was found between cortical grade II glioma (GC) and DNT regarding IDH1 and 2 TP53 alterations and 1p19q deletion. Similarly 50 % of no specific form of DNT share the same molecular profil with GC with CD34 expression and V600E mutation of BRAF. PXA demonstrated BRAFV600E mutation in 60 % of cases. PXA could then be very close glioneuronal tumors. Finally in PA we confirmed the negative impact of hypothalochiasmatic location, pilomyxoid diagnosis and age lower than 36 months and partial resection. We could work on the elaboration of a new classification and define the group named “Histone dependant” for tumors with histone aberrations and the group named “MAPKinases dependant” for tumors with either KIAA 1543-BRAF fusion or V600E BRAF mutation.In conclusion, this work has led to improve the molecular profil characteristics of glioneuronal tumors of childhood with different easy diagnostic markers that can be used in routine practice, and could potentially replace DNA sequencing
Cunha, Andrew Silva da. "Análise do papel da prostaglandina E2 e seus receptores na proliferação e apoptose em glioma humano, e da expressão das enzimas COX-1, COX-2, mPGES-1, mPGES-2 e cPGES." Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/42/42134/tde-17042013-105432/.
Повний текст джерелаGliomas are tumors of the central nervous system (CNS) that evolve from glial cells. The most common and most aggressive form of these tumors is known as glioblastoma multiforme (GBM). The biological aggressiveness of GBM is associated with its rapid growth and lack of apoptosis. Its poor prognosis is strongly associated with the difficulty of treating these cells as they are resistant to chemotherapy and radiotherapy. The gene expression of the enzymes cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), microsomal prostaglandin E synthase-1 (mPGES-1), microsomal prostaglandin E synthase-2 (mPGES-2), cytosolic prostaglandin E synthase (cPGES) and the products of the activity of these enzymes, including prostaglandin E1 (PGE1) and prostaglandin E2 (PGE2), are directly related to the malignancy of gliomas. PGE1 and PGE2 can act in an autocrine and paracrine manner, by interacting with their target cells via binding to cell surface receptors that are linked to G-proteins. These receptors are known as EP receptors and are divided into four subtypes: EP1, EP2, EP3 and EP4; each of which activates distinct intracellular signaling pathways. Therefore, this study aimed to analyze, in vitro, the role of PGE1, PGE2 and their receptors in the proliferation and apoptosis of human glioma and the expression of COX-1, COX-2, mPGES-1, mPGES-2 and cPGES.
Soldatelli, Jéssica Silveira. "Efeitos da combinação de temozolomida e ditelureto de difenila em linhagens celulares de glioblastoma." reponame:Repositório Institucional da UCS, 2018. https://repositorio.ucs.br/11338/4064.
Повний текст джерелаGliomas represent more than 70% of primary brain tumors. Malignant gliomas are characterized by low incidence, but high mortality rates. Despite the initial responsiveness to the standard treatment with the chemotherapeutic alkylating temozolomide (TMZ), few advances have been made in the prognosis of patients in the last 10 years. This is due to the fact that these tumors are rarely amenable to surgical resection and have a high rate of recurrence. Moreover, the effectiveness of this treatment encounters barriers such as undesirable side effects and chemotherapeutic resistance. In this scenario, the discovery of new substances that may act with additive or synergistic effect and increase the sensitization of tumor cells to the treatment becomes a therapeutic strategy in the field of oncology. Diphenyl ditelluride (DPDT) is a derivative of tellurium used in various reactions of organic synthesis and has interesting in vitro biological effects, as antioxidant, chemoprotective, cytotoxic and antitumor agent. Therefore this work aimed to evaluate the cytotoxic effects of this organotellurium compound and the chemotherapeutic, TMZ, in isolated and in association regimens, after acute and chronic exposure, of non-resistant (M059J) and TMZ- resistant (GBM) glioma cells. Through the cell viability assay, it was shown that TMZ is cytotoxic for both cell lines tested, showing a higher IC50 value in the resistant line when compared to the other line. This data was confirmed by the cumulative population doubling test. In addition, by the acridine orange staining, it was verified that autophagy might favor the chemoresistance, although not being the main resistance mechanism in the lines tested. It was observed that DPDT clearly has a dose-dependent cytotoxic effect on the M059J and GBM cell lines, in a lower concentration range than that used with TMZ. DPDT sensitized the cells to TMZ treatment as evidenced by the decline in cell viability. It is important to point out that this sensitization occurred in low and approximate IC50 values after both 24 h and 120 h of treatment, being the effects of the DPDT independent of the resistance profile to TMZ. Taken together, data from this work suggest the use of DPDT in association with TMZ as an interesting strategy to reduce the doses of TMZ used in the clinic and to reduce side effects to patients under treatment of glioma.
Lefranc, Florence. "Caractérisation de divers effets biologiques provoqués par la gastrine au niveau de gliomes et de gliosarcomes expérimentaux." Doctoral thesis, Universite Libre de Bruxelles, 2005. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/211044.
Повний текст джерелаNous avons au préalable tenté de caractériser par une technique de RT-PCR l’expression d’ARN pour divers récepteurs à la gastrine au sein de tumeurs du système nerveux central et périphérique (comprenant des gliomes, des méningiomes et des schwannomes), au sein de gliomes et d’un gliosarcome expérimentaux, et au sein de cellules endothéliales humaines de veines ombilicales HUVEC et de manchons vasculaires obtenus par microdissection au laser d’un glioblastome humain. Nous avons également développé un modèle de neurochirurgie expérimentale chez le rat consistant en la résection microchirurgicale de la tumeur cérébrale après un bilan iconographique par IRM. Nous avons ainsi montré que l’administration de gastrine dans le foyer opératoire après résection tumorale augmente significativement la période de survie de rats immunodéficients porteurs du modèle de gliome humain U373 et de rats conventionnels porteurs du modèle C6 de rat. In vitro, nous avons montré grâce au test colorimétrique MTT que la gastrine induit une diminution significative du taux global de croissance de ces deux modèles avec une accumulation des astrocytes tumoraux dans la phase G1 de leur cycle cellulaire. Par la technique de Western blotting nous avons également montré que la gastrine induit une diminution significative des taux protéiques du complexe cycline D3-Cdk4 dans les deux modèles expérimentaux. Nous avons montré que la gastrine est capable de réduire significativement l’invasion des modèles C6 de rat, U373 humain et de gliosarcome 9L de rat au travers d’une matrice de collagène et de réduire l’invasion des cellules U373 en chambre de Boyden. La gastrine modifie également significativement la motilité des cellules C6 et U373 et l’organisation de leur cytosquelette d’actine.
Nous avons découvert que la gastrine administrée en intracérébral dans le foyer tumoral U373 augmente significativement le taux d’angiogenèse au sein de la tumeur. Nous avons alors investigué l’effet de la gastrine et des antagonistes des récepteurs à cholécystokinine sur le taux d’angiogenèse in vitro en utilisant le modèle des cellules HUVEC cultivées sur Matrigel. L’effet pro-angiogénique in vitro et in vivo de la gastrine est significativement contrecarré par le produit L365,260, un antagoniste relativement spécifique du récepteur CCK-B de la gastrine. La gastrine est chémoattractante sur les cellules HUVEC et augmente significativement leur sécrétion d’IL-8. Toutefois l’effet pro-angiogénique de la gastrine serait en partie dépendant de la modification du taux d’expression des sélectines par les cellules HUVEC, et non de la sécrétion d’IL-8. Nous avons réalisé une revue de la littérature pour tenter de comprendre pourquoi les astrocytes tumoraux migrants sont résistants à la chimiothérapie conventionnelle. A la fin du chapitre Discussion, dans le sous-chapitre intitulé « Quels sont les espoirs thérapeutiques dans le cas des gliomes dits diffus? », nous tentons d’analyser les implications thérapeutiques potentielles qu’il serait possible de tirer du présent travail.
Doctorat en sciences médicales
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Skog, Johan. "The quest for new improved adenovirus gene therapy vectors against glioma tumours." Doctoral thesis, Umeå : Umeå University, 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-624.
Повний текст джерелаOliveira, Dennis [Verfasser], Björn Michael [Akademischer Betreuer] Kampa, Karl-Josef [Akademischer Betreuer] Langen, and Frank [Akademischer Betreuer] Müller. "In vivo imaging of brain tumors using the PSMA-selective PET ligands [68Ga]Ga-PSMA-HBED-CC and [18F]DCFPyL in rat glioma models / Dennis Oliveira ; Björn Michael Kampa, Karl-Josef Langen, Frank Müller." Aachen : Universitätsbibliothek der RWTH Aachen, 2019. http://d-nb.info/1195150741/34.
Повний текст джерелаAzar, Safa. "Tumeurs cérébrales de bas grade : élaboration de modèles in vitro et in vivo pour le développement de thérapies innovantes." Thesis, Montpellier, 2017. http://www.theses.fr/2017MONTT017.
Повний текст джерелаLow grade gliomas are low proliferating tumors affecting functional regions of young patients. In most cases, they tend to transform into a more malignant state following surgery. These tumors carry a key mutation in isocitrate dehydrogenase (70-80% of DLGG). Gliomas with IDH1 mutation have improved prognosis compared togliomaswith wild type IDH1. IDH1 protein acquires the ability to convert α-Ketoglutarate (α-KG) to 2-OH-glutarate (2-HG). The new onco-metabolite can interfere with the normal function of α-KG, leading to a general hypermethylation of the genome, thus inducing a blockage of the cellular differentiation. Very good reviews on the molecular mechanisms underlying high grade glioma invasion already exist but little is known about the cellular and molecular mechanisms in diffuse low grade gliomas. To that end, I characterized the profile of IDH1 mutated cells in the different types of DLGG. I have demonstrated that the tyrosine kinase, PDGFRα and EGFR receptors are abundantly expressed by tumor cells eventhough they are not activated. In contrast, a strong phosphorylation of Erk p42 / 44 proteins was detected in these tumors. This phosphorylation has a dual origin: tumor cells and their environment. The use of a series of markers allowed me to better define the state of differentiation of cancerous cells and to demonstrate a preferential expression of Sox8 in oligodendrogliomas while Sox9 is predominant in astrocytomas. In a second time, I have developed a method for the culture of low-grade diffuse gliomas and isolated five cell lines carrying the recurrent mutation IDH1 R132H. Recently Agios has identified very specific inhibitors (particularly AGI-5198) of the mutated IDH1 enzyme which, used in a murine glioma model, contributed to the demethylation of H3K9me3 histones with an increased expression of differentiation related genes as well as a reduction of the tumor mass. On the contrary, I have shown that AGI-5198 increases cell growth of patient cell lines, modifies the cellular migration and various signaling pathways.These studies shed new light on the phenotype of tumor cells, their diversity and The molecular mechanisms governing their proliferation
Selek, Laurent. "Traitement intra-tumoral des gliomes malins par infusion convective de bevacizumab, développement d'un modèle de gliome chez le gros animal, étude anatomique de la diffusion convective dans un encéphale humain." Thesis, Université Grenoble Alpes (ComUE), 2016. http://www.theses.fr/2016GREAS040/document.
Повний текст джерелаHigh grade gliomas are the most frequent primitive central nervous system tumor. The standard treatment is an association of surgery, radiotherapy and chemotherapy. The mains issues with these treatments are the infiltrative properties of the tumour in a highly functional parenchyma, the blood-brain barrier limiting the transvascular transport of chemotherapy and the inherent radioresistance of glioma cells.Upon different strategy to overpass the blood-brain barrier, a direct injection in the brain was advocated. In order to maximize this delivery, the concept of convection enhanced delivery was developed; it consists in a direct injection in the parenchyma with a low flow-rate.Bevacizumab is an anti-VEGF A antibody, VEGF is one of the most important angiogenic factors. The goal of this treatment is to inhibit the angiogenesis and slow down the tumor growth.We propose to study the use of this antibody in a direct intra-cerebral infusion.First, we focalize on the pharmacokinetic properties of an intratumoral injection by convection –enhanced delivery compared to a systemic administration. This shows an equivalent intratumoral concentration with systemic concentrations significantly lower with the intra-tumoral injection. An important result is the similar concentration in the controlateral hemisphere with the two routes of infusion. Convection-enhanced delivery is suitable to carry far from the infusion site high molecular weight proteins. An intra-tumoral bevacizumab may theoretically provide similar efficiency with less systemic side-effect.Then, the efficiency of an intra-tumoral infusion of bevacizumab is compared to a systemic injection on a mouse glioma model. In terms of survival the intra-tumoral treatment is significantly more efficient with an important decrease of angiogenesis and tumoral proliferation.If convection-enhanced delivery rodent study were promising, clinical trials failed to show any efficiency of intra-tumoral injection mainly due to inadequate delivery secondary to backflows and leakages. One of the limits of the rodent model is the absence of cortical sulci, main leakage provider. The development of a model anatomically relevant could simulate real conditions of injection and develop implantable device of injection in realistic conditions. We have developed the first induced model of glioma in a large animal. We choose the pig for the similarity of its brain anatomy and its size. The animals have been treated with ciclosporin to induce an immunosuppression, human glioma cells have been implanted, leading to the development of brain tumor.We have studied the pressure on the infusion line and correlate it to backflow and leakage. We have identified a pattern of pressure for successful infusion. Different pressure pattern have systematically led to backflow or leakage. These pressures criteria could permit to us an early detection of inadequate infusion to replace the catheter and avoid the failure of precedent clinical trials.Next step have been the intra-tumoral injection via an implanted device on pig glioma model. No infectious complication has been related with a good local and neurologic tolerance. The injections have led to a relevant diffusion through the tumor with a rapid flow to the periphery due to the interstitial pressure gradient between the tumor and the periphery.Last step of this work have been the anatomical study of a dye distribution by convection-enhanced delivery in a human encephalon. Indeed if pig brain is similar to human brain, human white matter structure is unique. This work is focalized on the diffusion from the corona-radiata to the main white matter tracts. The distribution is anisotropic following white matter but the diffusion is different depending on the position of the catheter. The infusion seems to open low rheological impedance paths the position of the catheter have to be adapted to the white matter tract to target
Zouaoui, Sonia. "Epidémiologie clinique des tumeurs primitives du système nerveux central et en particulier des gliomes." Thesis, Montpellier, 2015. http://www.theses.fr/2015MONTT002.
Повний текст джерелаGliomas have devastating consequences. Morbidity and mortality are high. Gliomas represent a complex heterogeneous group of pathologic entities and no underlying cause has been identified for the majority of them. Epidemiologic data vary from study to study. The number of each histological subtype is too small, even for a big neurosurgical center, to allow a good research on each subtype of glioma. Oncological and clinical specificities (epilepsy, cognitive disorders, motor impairments, etc) require a specific care and analysis. Indeed, we need to collect and record all new cases and follow up in large area, to allow good basic and clinical studies. Furthermore, population study is the only way to know what clinicians do to the patients, and make possible evaluating the medical care. The French societies involved in Neuro-Oncology (Société Française de Neurochirurgie, Société Française de Neuropathologie, Association des Neuro-Oncologues d'Expression Française) have recently created the French Brain Tumor DataBase (FBTDB). The main objective of the FBTDB is to prospectively record all primary central nervous system tumors (PCNST), in France, for which histological diagnosis is available (1-3). The long-term goals of the FBTDB are to create a histological national registry and a national network to (1) perform epidemiological studies, (2) implement a new database and use it for setting up both clinical and basic research protocols, (3) allow the evaluation of the medical practices of an area or of the entire country, and (4) harmonize the healthcare of patients affected by PCNST at the higher level. The present PhD student, Sonia Zouaoui, will focus her work on gliomas. First, she will collect data, and will analyze prognostic factors, survival and oncological patterns of care for patients with newly diagnosed glioma in France. Secondly, she will participate in the study of geographical distribution of the main types of glioma and in search of causal factors. Thirdly, she will conduct an inventory of cryopreserved material available for translational research
Marand, Sandie. "Identification et caractérisation fonctionnelle de protéines d'intérêt pour le diagnostic et la thérapie des tumeurs gliales." Université Joseph Fourier (Grenoble ; 1971-2015), 2009. http://www.theses.fr/2009GRE10043.
Повний текст джерелаGliomas, particulary glioblastoma, are public health problem because of their dark pronostic. Difficulties to classify and lack of anti-tumor therapy efficiency are due to ignorance about these tumors. To improve diagnosis and also to understand the process leading to glioma formation and so to find new treatment, we choose to study patient sera immuno-reactivity. So we discovered about a hundred of proteins which immune status change between normal and pathological condition. Identifying and studying these proteins, we highlight important mechanisms for cancer and define key targets for therapy. Among these proteins, we studied immuno-reactivity to ten which leads us to define two types of antigens : those which immune status changes with tumor appearance and those who change depending on the sensibility to treatment of the tumor. We then choose three of these proteins for detail analysis : eef1a1, crhsp24, mark3. These three antigens are overexpressed in gliomas. Expression inhibition by siRNA induced a diminution of tumoral cell proliferation, indicating that they are implicated in this mechanism regulation. This essential function makes these potential therapeutic targets. First tests of vaccination toward mark3 show that studying this antigen is of particular interest despite results are not those wished. We show here that auto-antibody associated to glioma presence can be found in sera. These antibodies clearly have diagnosis interest but also can have prognostic interest. Their biological analysis could lead to consider them like potential therapeutic targets
Woxius, Jonathan. "Att tvingas dela hjärna med en inkräktare : En undersökning av den psykologiska aspekten av att leva med en hjärntumör." Thesis, Högskolan i Halmstad, Akademin för hälsa och välfärd, 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:hh:diva-42197.
Повний текст джерелаBackground: Primary malignant brain tumor carries a heavy symptom burden that presents itself in a big variation of physical, cognitive and neurological symptoms that affects the patients functioning and psychological wellbeing. Along with the emotional and existential stress of living with cancer, patients diagnosed with brain cancer also suffer from cognitive dysfunction. Purpose: The aim of this study was to illustrate the psychological strain of adult patients living with primary malignant brain tumor. Method: The study was executed as a general literature review based on ten scientific articles. The articles were quality-tested and analyzed to later be sorted into three main themes. Results: The first theme, The uncertainty in the prognosis, illuminate the uncertainty that occurred due to an unpredictable future and the need of information concerning treatment options and what symptoms to expect. The theme The psychosocial consequences, describes how the patients felt as though they had lost themselves to the disease due to memory loss, personality disorders and the inability to maintain the lifestyle they previously had. The patients shared a fear of being a burden to the people around them and a concern of losing their independency. The existential confrontation speaks about the inevitable thoughts of death and the importance of hope.
Le, Mercier Marie. "La galectine-1 influence fortement les caractéristiques biologiques des cellules gliales tumorales humaines." Doctoral thesis, Universite Libre de Bruxelles, 2009. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/210330.
Повний текст джерелаNous avons tout d’abord montré que la galectine-1 est impliquée dans la chimiorésistance des gliomes. En effet, nous avons démontré que la diminution du taux d’expression de la galectine-1, au moyen d’un siRNA au sein d’un modèle de gliome expérimental, permet d’augmenter le bénéfice thérapeutique du témozolomide in vivo sans toutefois induire d’apoptose, d’autophagie ou de perméabilisation de la membrane des lysosomes. Nous avons également montré que la diminution du taux d’expression de la galectine-1 au sein de ce modèle de gliome expérimental affecte les processus d’angiogenèse in vivo et de « vasculogenic mimicry » in vitro. Nous avons identifié la protéine ORP150 comme l’une des principales cibles de l’effet pro-angiogénique de la galectine-1, sachant que la protéine ORP150 contrôle la maturation du facteur VEGF. Nous avons ensuite montré que le rôle de la galectine-1 dans la chimiorésistance des gliomes et dans l’angiogenèse est directement lié à l’implication de la galectine-1 dans le processus de réponse au stress du réticulum endoplasmique. Via ce processus, la galectine-1 modulerait l’expression d’un certain nombre de gènes tels que ATF3, DUSP5 et HERP, qui sont impliqués dans la chimiorésistance et des gènes tels que ORP150 et MDG1 qui sont impliqués dans l’angiogenèse.
Enfin, nous avons également montré que la galectine-1 régule l’expression du gène BEX2 et que celui-ci joue un rôle important dans la biologie des gliomes, notamment dans les processus d’angiogenèse et de migration cellulaire.
En conclusion, notre travail suggère que l’étiquette « biomarqueur » pourrait être attribuée à la galectine-1 pour qualifier l’agressivité biologique des gliomes malins et que la galectine-1 pourrait représenter une nouvelle cible thérapeutique dans le combat contre les gliomes malins en général, et le glioblastome en particulier.
Doctorat en Sciences biomédicales et pharmaceutiques
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Carvalho, Guilherme Luiz de Castro. "Estudo de análogo da subtância P para desenvolvimento de radiofármaco com aplicação na terapia de tumores cerebrais." Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/85/85131/tde-25092015-090446/.
Повний текст джерелаCurrently gliomas represent about 81% of malignant brain tumors with increased incidence in children and in adults over 45 years. A large number of type 1 neurokinin receptor (NK-1) are expressed in glioma cells, being the binding of substance P (SP) to these receptors, involved in the development and progression of this tumor type. The SP conjugated at DOTA chelator (SP-DOTA), radiolabeled, have been tested for use in the treatment of gliomas, and the lutetium-177 (177 Lu), due to its lower tissue range, has been the most suitable radioisotope for tumors located in critical areas brain. However, studies indicate the necessity of adding an excess of methionine to prevent the peptide SP-DOTA-177Lu oxidation in order to increase the stability and capacity to bind to tumor cells. To overcome this challenge, there is the prospect of using a new analog of SP with a modified structure, to prevent peptide oxidation. In this context, the aim of this work was study the labeling of a new analog of SP with 177Lu and characterize their properties in vitro and in vivo, in order to obtain a novel radiopharmaceutical with potential application in brain tumor therapy, and perform preliminary studies labeling of this new analog with yttrium-90 (90Y). The new analog was obtained by replacement of the amino acid methionine (Met) by the amino acid norleucine (Nle) at position 11 of the peptide chain of SP, and these peptides were called SP(Met11)-DOTA and SP(Nle11)-DOTA respectively. After analysis of the oxidation for the two peptides, the radiolabeling parameters of the SP(Nle11)-DOTA with 177LuCl3 were studied to determine the best labeling condition. The SP(Nle11)-DOTA was also radiolabeled with 90Y, using standard condition, and the stability in vitro of the SP(Nle11)-DOTA-90Y assessed under refrigeration (2-8 °C) and under freezing (-20° C), after radiolabeling with high activity and use of stabilizing agent. The stabilities in vitro of the SP (Nle11)-DOTA-177Lu under refrigeration (2-8 °C), under freezing (-20 °C) and in human serum (37 °C) were determined after radiolabeling with high activity, with use of stabilizing agents and after dilution. The ability of in vitro binding to tumor cells (U-87 MG and M059J) and the biodistribution in vivo in healthy BALB/c mice were determined for the 177Lu-DOTA-SP(Nle11) and compared to 177Lu-DOTA-SP(Met11). The plasma protein binding and biodistribution in Nude mice with tumor model were also evaluated. The results obtained from analysis of oxidation for the two peptides confirmed the importance of adding excess methionine to prevent peptide oxidation and indicated a high stability of the DOTA- SP(Nle11), during and after the radiolabeling process. The addition of 148 MBq (4 mCi) of 177LuCl3 solution in 0.05N HCl at 10 μg DOTA-SP(Nle11) diluted in 0.4 M sodium acetate buffer pH 4.5 followed by incubation at a temperature of 90 °C for 30 minutes under constant agitation to 350 rpm was defined as standard labeling condition. The freezing (-20 °C), the use of stabilizing agents and the dilution were presented as effective methods to ensure high stability in vitro 177Lu-DOTA-SP(Nle11), after labeling with high activity. Good results were also observed for labeling DOTA-SP(Nle11) with 90YCl3 and for stability in vitro of the 90Y-DOTA-SP(Nle11) after freezing (-20 °C) and when gentisic acid was used as a stabilizer. The 177Lu-DOTA-SP(Nle11) showed good specificity to tumor cells, particularly human glioma cells (M059J), suggesting that substitution of the amino acid norleucine for methionine at position 11 does not compromise the capacity of SP(Nle11) binding to tumor cells. A low percentage of plasma protein binding and rapid blood clearance were observed for the 177Lu-DOTA-SP(Nle11), being this radiopharmaceutical preferably eliminated by the kidney. The 177Lu-DOTA-SP(Nle11) showed good stability in vivo and inability to cross the blood brain barrier, being its use indicated through intratumoral or intracavitary injection. The biodistribution studies in animals with tumor model showed that the radiopharmaceutical binds to the tumor cells by specific receptor binding. Based on this data was concluded that the 177Lu-DOTA-SP(Nle11), can be presented as a novel radiopharmaceutical that due to its favorable properties in vitro and in vivo, presents a potential application in the therapy of brain tumors, representing a new possibility within the limited therapeutic options for this type of tumor.
Bautista, Cynthia A. "Survivorship of a low-grade glioma brain tumor /." View online ; access limited to URI, 2004. http://0-wwwlib.umi.com.helin.uri.edu/dissertations/dlnow/3135892.
Повний текст джерелаSoares, Bruno Lobão. "Efeito dos glicosaminoglicanos (GAGs) sobre a progressão do glioma C6." Florianópolis, SC, 2001. http://repositorio.ufsc.br/xmlui/handle/123456789/79792.
Повний текст джерелаMade available in DSpace on 2012-10-18T07:33:38Z (GMT). No. of bitstreams: 0Bitstream added on 2014-09-25T23:18:04Z : No. of bitstreams: 1 177718.pdf: 8076514 bytes, checksum: 1ef6e9f15f6eb6e5e5dc581e5e56bbf3 (MD5)
O presente estudo tem por objetivo verificar efeitos dos glicosaminoglicanos sobre a adesão in vitro do glioma C6. Analisamos também, os efeitos da subsulfatação dos GAGs na implantação intracerebral do glioma. Sendo a adesão um passo crítico para o estabelecimento inicial tumoral, realizamos ensaios de adesão celular para testar propriedades de proteínas da Matriz Extracelular (MEC) (laminina, fibronectina e colágeno tipo IV), assim como de GAGs (heparina e condroitin-sulfato) na adesão das célula C6 em placas de ELISA. As proteínas da MEC estimularam a adesão de C6 de modo crescente. A heparina apresentou diferentes efeitos de interação com cada proteína da MEC testada, inibindo a adesão a laminina, aumentando a colágeno IV e não alterando a Fibronectina. Por outro lado, a presença de condroitin-sulfato reduziu a adesão de C6 de modo dose-dependente, às três proteínas testadas. Os experimentos de pré-incubação da heparina às proteínas da MEC ou às células, podem sugerir que interações entre a MEC e GAGs podem ser específicas para determinar a adesão celular. Trabalhos anteriores do nosso laboratório mostraram que o tratamento in vitro de células C6 com clorato de sódio (inibidor de sulfatação de GAGs) reduz a adesão e a proliferação de um modo dose-dependente sem induzir morte celular. Assim, nós testamos os efeitos do tratamento in vivo com o clorato de sódio sobre o crescimento do glioma C6, e procuramos verificar alguns aspectos imunológicos. Realizamos inoculações subcutâneas (2 X 107 células) e intracerebrais (1 X 105 células) de células C6 e analisamos os hemogramas, testes anatomopatológicos, histopatológicos, de sobrevivência e de comportamento. No tratamento local subcutâneo, clorato de sódio revelou ser eficiente em reduzir o crescimento tumoral 30 dias após a inoculação de células C6. Nas inoculações intracerebrais, o pré-tratamento de células C6 com clorato de sódio e tratamento posterior no sítio tumoral, reduziu o crescimento do glioma, revelado pelos testes de sobrevivência e histopatologia. Sensibilizações prévias, intraperitoneais, com células C6 pré-tratadas com clorato de sódio ou com células controle, inibiram o crescimento do glioma após a inoculação intracerebral de células C6, como mostrado nos experimentos de sobrevivência e nas histopatologias. Os hemogramas revelaram uma redução linfocitária 24 e 28 dias após a inoculação intracerebral de C6, porém sem diferenças na leuco e linfometria entre os grupos sensibilizados, entre si e em relação ao controle. Os testes comportamentais revelaram redução em parâmetros exploratórios nos animais inoculados intracerebralmente com C6 quando comparados com o grupo que recebeu C6 pré-tratado com clorato de sódio ou com o grupo controle-operado(sham). Estes resultados sugerem que a sulfatação dos GAGs pode ser importante para o estabelecimento e progressão do glioma C6 in vivo.
Neshasteh-Riz, Ali. "Radiolabelled iododeoxyuridine for experimental targeted radiotherapy of glioma." Thesis, University of Glasgow, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.364086.
Повний текст джерелаWehbe, Katia. "Usage of FTIR spectro-imaging for the development of a molecular anatomo-pathology of cerebral tumors." Thesis, Bordeaux 1, 2008. http://www.theses.fr/2008BOR13677/document.
Повний текст джерелаMalignant gliomas are very aggressive tumors with poor prognosis, highly angiogenic and invasive into the surrounding brain parenchyma, making their resection very difficult. Regarding the limits of current imaging techniques, we have proposed Fourier Transform Infrared (FTIR) spectro-imaging, with a spatial resolution of 6 µm, to provide molecular information for the histological examination of gliomas. Our work was based on the research of molecular parameters of blood vessels, notably on the basis of the contents of their basement membrane, which undergoes changes due to tumor angiogenic stress. We have identified alterations of the secondary structure of proteins (such as collagen) in blood vessels during tumor growth. We have also assessed the changes in fatty acyl chains of membrane phospholipids, which revealed a higher unsaturation level in tumor vessels. Then, on a murine glioma model, we have established an efficient method of blood vessels classification based on their carbohydrates and fats contents, allowing the differentiation between healthy and tumor blood vessels. The combination of these parameters was used to provide a molecular histopathology for the study of human gliomas. Our results have demonstrated the feasibility of differentiating between healthy and tumor vasculature in these human gliomas, which help delimitating areas of corresponding tissue. This technique could become a reliable and fast analytical tool, with duration compatible with the surgery and thus very useful for neurosurgeons
Saavedra, López Elena. "Stimulation of Glioma-Associated Microglia/Macrophages effector phagocytic synapse towards tumor clearance in glioma." Doctoral thesis, Universitat Autònoma de Barcelona, 2019. http://hdl.handle.net/10803/667801.
Повний текст джерелаGlioblastoma (GBM) is the most aggressive form of glioma and currently has no cure. Given that around 30% of the cells within the tumor are microglia/macrophages (glioma- associated microglia/macrophages or GAMM from now on), we decided to study them in order to shed light in possible future immunotherapies. The first discovery during this investigation was the presence of GAMM in pseudopalisades (PPs) of human GBM. These structures are thought to be very important in the contribution of the tumor invasiveness, therefore the knowledge of the role of GAMMs here might be crucial. Particularly, GAMMs were found to be traveling through the PPs towards the necrotic focus, contrasting with the tumor cells. Moreover, the myeloid cells seem to gain cellular persistence with the hypoxic gradient and travel in a haptotactic manner using the gradient of glioma cells as a cue. When they reach the necrotic focus, they shift their phenotype and phagocytose tumor material, including GFAP+ fragments and nuclei. Secondly, by means of cell cultures we achieved to translocate p65 NF-κB and promote phagocytosis of tumor glioma cells (C6) by primary microglia. Moreover, using cell lines (BV-2 and GL261) we described the putative steps of phagocytosis and the distribution of some receptors (CD11b and CD16/32) involved in the process of phagocytosis. Importantly, the distribution of Iba-1 in interacting GAMMs was also defined in the animal models. Finally, we tested two immunotherapy strategies in a immunocompetent GBM animal model (C57/BL6 intracraneally inoculated with GL261 cells), and discovered that both immunotherapies have different outcomes: while CD47 neutralizing antibody seemed to be non-effective, neutralizing SIRP1α had a beneficial outcome. This way, anti-CD47 treated animals did not have any increase on survival rate than control groups; and they showed decreased bodyweight throughout the experiment, suggesting that the therapy had some systemic side effects. On the other hand, blocking SIRP1α allowed the increase of the bodyweight of the animals throughout the experiment, and decreased the cellularity of the tumor core by increasing the phagocytic activity of GAMM at the peripheral area of tumor invasion without interfering in their infiltration capacity. In all, this thesis contributes to a better understanding of the role of GAMMs in GBM and the intrinsic phagocytic capacity they can play, possibly helping in the development of immunotherapeutic tools to fight this fatal tumor.
Mulligan, Karl Andrew. "A new glioma-associated cell surface glycoprotein." Thesis, Queen's University Belfast, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.286823.
Повний текст джерелаHunt, G. "The metastatic inefficiency of malignant glioma." Thesis, University of Newcastle Upon Tyne, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.377441.
Повний текст джерелаLima, Rute Maria Ferreira. "Caracterização fenotípica de esp12, uma nova linhagem de células tumorais de glioblastoma humano, e desenvolvimento de um modelo in vitro para avaliar a resistência de gliomas a quimioterápicos." Centro de Pesquisas Gonçalo Moniz, 2014. https://www.arca.fiocruz.br/handle/icict/8176.
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Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil
O astrocitoma grau IV ou glioblastoma multiforme (GBM) é o mais maligno e com prognóstico ruim entre os gliomas. Esse prognóstico sombrio está associado, em parte, à quimiorresistência (QR). Ao lado disso, a classificação atual dos gliomas não consegue responder a heterogeneidade da resposta ao tratamento. Assim, parece existir subtipos de GBM com características distintas. Dessa forma, o objetivo desse trabalho foi caracterizar fenotipicamente uma nova linhagem, ESP12, e, desenvolver um modelo in vitro para a avaliação da QR. Amostras obtidas de glioma humano foram estudadas quanto aos achados característicos de malignidade e subtipadas quanto aos fenótipos proliferativo e pró-neural, imunohistoquimicamente. As culturas obtidas das amostras foram mantidas a 37 ºC em atmosfera com 5% de CO2. A caracterização de ESP12 incluiu: a) subtipagem por imunocitoquímica e por citometria de fluxo; b) investigação de um fenótipo de resistência, através da identificação de células CD133+ e de proteínas de resistência às múltiplas drogas, glicoproteína-P (Pgp) e MRP1; c) avaliação da cinética de crescimento, através da determinação do tempo de duplicação celular (TDPC); d) verificação da produção do fator de crescimento endotelial vascular (VEGF); e) avaliação da viabilidade celular, através do teste com MTT, quando exposta a carmustina (BCNU), a vimblastina (VIM) e a temozolomida (TMZ). Por fim, investigamos a atividade quimiossensibilizante do 8-metoxipsoraleno (8-MOP) utilizando o modelo estabelecido. Foram obtidos 6 casos de GBM e 3 casos de gliomas de graduação III, pela Organização Mundial de Saúde, com idade média de 52,6 14,1 anos, a maioria homens. As manifestações clínicas mais frequentes foram crises convulsivas e cefaleia, e, a localização tumoral foi variada. Os achados de imagem se correlacionaram com os achados histoquímicos confirmando o diagnóstico. A sobrevida dos pacientes variou entre 11 dias e 24 meses, com mediana de 11,5 meses. As células formaram monocamadas e revelaram intenso pleomorfismo. A maior parte das amostras apresentou fenótipo proliferativo na imunohistoquímica. As proteínas que caracterizam os fenótipos pró-neural, proliferativo e mesenquimal foram detectadas tanto por imunohistoquímica quanto por imunocitoquímica, em ESP12. Quantitativamente, o fenótipo proliferativo foi mais evidente detectado por citometria de fluxo. Células CD133+ representaram menos que 1%. Além disso, 38,6% das células foram positivas para a Pgp. Não houve diferença entre a produção do VEGF por ESP12 quando comparada a outras linhagens de GBM já estabelecidas. O TDPC de ESP12 foi de 31 h. ESP12 se mostrou mais sensível do que outras linhagens de GBM já estabelecidas a BCNU, a VIM e a TMZ. Por fim, o 8-MOP mostrou atividade quimiossensibilizante significativa.
The astrocytoma grade IV also known as glioblastoma multiforme (GBM) is the most malignant and has a poor prognosis among gliomas. This poor prognosis is associated, in part, to chemoresistance (QR). Furthermore, the current classification of gliomas cannot answer the heterogeneity of treatment response. Therefore, it seems to exist GBM subtypes with distinct characteristics. The aim of this study was to characterize phenotypically a new cell line, ESP12, and to develop an in vitro model for the assessment of QR. Human glioma samples were studied by immunohistochemistry for the characteristic findings of malignancy and subtyped as to proliferative and proneural phenotypes. Primary cultures were obtained from samples and maintained at 37 °C in an atmosphere with 5% CO2. The characterization of ESP12 included: a) subtyping by immunocytochemistry and flow cytometry; b) investigation of a resistance phenotype by identifying CD133+ cells and the multidrug resistance proteins, P-glycoprotein (Pgp) and MRP1; c) evaluation of the growth kinetics, by determining the cell doubling time (TDPC); d) assaying of vascular endothelial growth factor (VEGF) production; e) the assessment of cell viability by the MTT test after exposure to carmustine (BCNU), vinblastine (VIM), and temozolomide (TMZ). Finally, we investigated the chemosensibilizing activity of 8-methoxypsoralen (8-MOP) using the established model. Six cases of GBM and 3 cases of grade III gliomas were obtained, with a mean age of 52.6 14.1 years, mostly men. The most common clinical manifestations were seizures and headache, and the tumor location was varied. Imaging findings were correlated with the histochemical findings confirming the diagnosis. The median survival was 11.5 months (range: 11 days to 24 months). The cells formed monolayers and showed intense pleomorphism. Most samples showed proliferative phenotype in immunohistochemistry. Proteins that characterize the proneural, proliferative and mesenchymal phenotypes were detected both by immunohistochemistry and by immunocytochemistry on ESP12. The proliferative phenotype was more quantitatively evident by flow cytometry. CD133+ cells represented less than 1%. Moreover, 38.6 % of cells were positive for Pgp. There was no difference between the production of VEGF between ESP12 and other GBM cell lines already established. The TDPC of ESP12 was 31 h. ESP12 was more sensitive than other cell lines already established of GBM to BCNU, TMZ and VIM. Finally, the 8-MOP showed significant chemosensibilizing activity.
Florian, Catarina Ligia. "Proton nuclear magnetic resonance studies of human glioma cell lines." Thesis, University College London (University of London), 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.309218.
Повний текст джерелаKoochekpour, Shahriar. "Evaluation of mechanisms underlying the proliferative and invasive behaviour of glioma." Thesis, University of London, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.309429.
Повний текст джерелаFreitas, Rodrigo Maciel de. "Estudo da atividade glial em função do conteúdo de S100B, GFAP e glutamina sintetase em astrocitomas humanos." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2006. http://hdl.handle.net/10183/11104.
Повний текст джерелаResende, Fernando Francisco Borges. "Biologia do glioblastoma multiforme – da dinâmica de ativação microglial ao papel do canal de potássio Kv 10.1." reponame:Repositório Institucional da UnB, 2016. http://repositorio.unb.br/handle/10482/20136.
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O glioblastoma multiforme é o tumor cerebral mais agressivo. Já a micróglia representa 30% da massa tumoral e desempenha um importante papel na tumorigênese. Este trabalho buscou estudar o padrão de infiltração e alteração morfológica da micróglia no tecido tumoral formado por células da linhagem GL261mCherry implantadas ortotopicamente. Além disto, buscou-se examinar o papel do canal de potássio Kv 10.1, correlacionado ao crescimento tumoral, primeiro na interação da micróglia com as células tumorais e, segundo, frente à lesão celular causada pelo fármaco de escolha ao tratamento do glioma, a temozolomida. Camundongos CX3CR1-EGFP receberam injeções intracorticais de células de glioblastoma multiforme capazes de expressar a proteína fluorescente mCherry. Microscopia de epifluorescência e confocal foram empregadas nas análises morfométricas, ao passo que a microscopia do tipo 2-photon (2P-LSM) foi usada para visualizar as células tumorais e microgliais no cérebro de animais vivos. Os resultados deste estudo revelaram uma microgliose intensa em áreas cerebrais logo após a implantação do tumor, isto é, aos 30 minutos. Nos primeiros três dias, a micróglia tende a formar aglomerados de células em torno dos tumores. Para, em seguida, infiltrar no centro tumoral, onde permanece durante todos os pontos de tempo estudados, de 6 a 18 dias. Com o aumento da massa tumoral, as células tumorais perdem progressivamente a sua forma original, assumindo uma morfologia heterogênea e difusa; o tamanho do corpo celular (perímetro) passou de 10 µm, três dias após o implante, para 52 µm aos 18 dias. Em contato com o glioma, a micróglia também muda sua morfologia. A forma tornou-se amebóide, com corpos celulares alargados. O corpo celular (área) cresceu de 366±0.0 µm2, na micróglia em vigilância, para 1310±146.0 µm2 e ramificações curtas, ou mesmo ausência de ramificações no fenótipo ativado. Aos 12 dias após o implante, foi notada a presença de células multinucleadas de glioma, os policariócitos, em contato íntimo com a micróglia ativada. Sobre o canal Kv-10.1, este foi expresso em células cultivadas de glioma, de micróglia (linhagem BV-2) e também em tecido tumoral de camundongos implantados com o tumor. A supressão deste canal, em células de glioma, potencializou a injúria por TMZ em 29%, conforme ensaio de MTT. Em conclusão, a micróglia apresentou um padrão espaço-temporal de infiltração no glioma, o que favorece influências recíprocas e pró-tumorigênicas. Já o canal Kv-10.1, pode tanto representar uma via de comunicação entre estes tipos celulares, quanto ser um potencial alvo para a terapêutica do glioma, já que foi capaz de potencializar os efeitos da temozolomida na morte celular de linhagens de glioma.
Glioblastoma multiforme is the most aggressive brain tumor. Microglia represents 30% of the tumor mass, and plays a role in tumorigenesis. This work studied the pattern of microglial growth into brain tumor tissue formed by orthotopically implanted glioma cells of the established GL261 cell line. In addition, we examined the expression of the Kv 10.1 potassium channel that frequently correlates with tumor growth. CX3CR1-EGFP mice received intracortical injections of GL261 tumor cells with stable expression of the red fluorescent protein mCherry. Epifluorescence - and confocal laser-scanning microscopy were employed in the analysis of tissue sections, whereas two-photon laser-scanning microscopy (2P-LSM) was used to visualize tumor cells and microglia in the brain of living animals. Our results revealed an intense microgliosis in brain areas already shortly after tumor implantation, i.e. at 30 minutes. In the first three days, microglia formed clusters of cells around tumors mass. Then cells infiltrated the tumor area, where they remained during all the time points studied, from 6 to 18 days. As tumor increased in size, GL261 cells progressively lost their original shape, assuming a heterogeneous and diffuse morphology. Soma size increased from 10 to 52 µm. In contact with the glioma, microglia also changed its morphology. Cell bodies enlarged from 366±0.0 µm2, in quiescent microglia, to 1310±146.0 µm2. The shape became amoeboid, with enlarged cell bodies and short processes (or even absence of them). Remarkably, we found microglial processes that closely surrounded glioma cells. Microglia also grew around multinucleated polycariocytes, found in tumors at 12 days. The Kv 10.1 channel was expressed in cultured GL261 cells, microglia cell line (BV-2) and also in mouse tumors. Suppression of Kv10.1 caused a 29% decrease in the viability of glioma cells injured by TMZ. In conclusion, microglia presented a temporal and spatial pattern of infiltration in glioma tumors, which favors reciprocal and protumorigenic influences. Kv 10.1 expressed by glioma cells in close contact with microglia may represent a communication pathway between microglia and cancer cells and, could be a potential target for antiglioma gene therapy, since it potentiated the effects of temozolomide in glioma cell lines.
Clark, Aaron J. "The Expression and Function of Wilms' Tumor 1 in Malignant Glioma." VCU Scholars Compass, 2006. http://hdl.handle.net/10156/1665.
Повний текст джерелаDumont-Girard, Philippe. "Chimiothérapies intra-veineuses des tumeurs astrocytaires de haut grade : revue de la littérature et évaluation d'un protocole associant fotémustine, platine et VP16." Montpellier 1, 1998. http://www.theses.fr/1998MON11064.
Повний текст джерелаBerger, François. "Étude et caractérisation de mécanismes suppresseurs dans les tumeurs cérébrales humaines et le cerveau non tumoral : anti-tyrosine kinase, p53 et ciblage exogène par le thymidine kinase herpétique." Université Joseph Fourier (Grenoble), 1995. http://www.theses.fr/1995GRE10109.
Повний текст джерелаLedur, Pítia Flores. "Células tronco tumorais e o sistema purinérgico." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2009. http://hdl.handle.net/10183/17066.
Повний текст джерелаGlioblastoma multiformes are the most aggressive tumors in the CNS and are characterized by high invasion and proliferation rates, as well as for being resistant to chemo and radiotherapies. This leads to one of the worst prognosis among cancers. Cancer stem cells (CSCs) are scarce among the tumor cells, but can undergo differentiation and self-renewal, being fundamental for tumor maintenance. Tumorspheres, which resemble neurospheres, can grow in glioma cell cultures and are rich in CSC. Additionally, CSCs seem to be more resistant to radiotherapy and strategies aimed at differentiating these stem cells have potential to produce less aggressive and more efficient treatment regimes. CSCs have been identified in different tumor types as well as in established cell lines such as the human glioma cell line U87, and are characterized by the presence of the CD133 glycoprotein. Purinergic receptors are stimulated by nucleotides and nucleosides, and are involved in many biological processes, including embryonic development. ATP induces several cellular responses, such as proliferation and differentiation, and it has been demonstrated that the degradation of this nucleotide is slow in glioma cells, which results in its accumulation in the extracellular space. The aim of this work was to characterize the CSC population in U87 and the effect of ATP in sphere formation. Spheres were obtained by plating cells on a thin layer of agar. Tumorspheres presented a higher amount of CD133 marker as analyzed by flow citometry and western blotting. mRNA expression of OCT-4, a marker of undifferentiated cells, was higher in spheres, while GLAST and CAMKII, markers of differentiated glial and neuronal cells respectively, presented higher expression in the monolayer cells. Cells plated in the presence of ATP 100 µM formed 54% less spheres (P<0.05) when compared to control and also had a reduced level of CD133 marker. Among the purinergic receptors, P2X4 expression was higher in spheres, whereas P2X6 expression was higher in the monolayer. Our results indicate that spheres have components of stem cells and that the purinergic signaling is involved in important aspects of CSC biology.