To see the other types of publications on this topic, follow the link: Brain cancer.
Dissertations / Theses on the topic 'Brain cancer'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 dissertations / theses for your research on the topic 'Brain cancer.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse dissertations / theses on a wide variety of disciplines and organise your bibliography correctly.
1
Shelton, Laura Marie. "Targeting Energy Metabolism in Brain Cancer." Thesis, Boston College, 2010. http://hdl.handle.net/2345/1183.
Full textAbstract:
Thesis advisor: Thomas N. SeyfriedIt has long been posited that all cancer cells are dependent on glucose for energy, termed the "Warburg Effect". As a result of an irreversible injury to the mitochondria, cancer cells are less efficient in aerobic respiration. Therefore, calorie restriction was thought to be a natural way to attenuate tumor growth. Calorie restriction lowers blood glucose, while increasing the circulation of ketone bodies. Ketone bodies are metabolized via oxidative phosphorylation in the mitochondria. Only cells that are metabolically capable of aerobic respiration will thus be able to acquire energy from ketone bodies. To date, calorie restriction has been shown to greatly reduce tumor growth and angiogenesis in the murine CT2A, EPEN, and human U87 brain tumor models. Using the novel VM-M3 model for invasive brain cancer and systemic metastatic cancer, I found that though calorie restriction had some efficacy in reducing brain tumor invasion and primary tumor size, metastatic spread was unaffected. Using a bioluminescent-based ATP assay, I determined the viability of metastatic mouse VM-M3 tumor cells grown in vitro in serum free medium in the presence of glucose alone (25 mM), glutamine alone (4 mM), or in glucose + glutamine. The VM-M3 cells could not survive on glucose alone, but could survive in glutamine alone indicating an absolute requirement for glutamine in these metastatic tumor cells. Glutamine could also maintain viability in the absence of glucose and in the presence of the F1 ATPase inhibitor oligomycin. Glutamine could not maintain viability in the presence of the Krebs (TCA) cycle enzyme inhibitor, 3-nitropropionic acid. The data indicate that glutamine can provide ATP for viability in the metastatic VM-M3 cells through Krebs cycle substrate level phosphorylation in the absence of energy from either glycolysis or oxidative phosphorylation. I therefore developed a metabolic therapy that targeted both glucose and glutamine metabolism using calorie restriction and 6-diazo-5-oxo-L-norleucine (DON), a glutamine analog. Primary tumor growth was about 20-fold less in DON treated mice than in untreated control mice. I also found that DON treatment administered alone or in combination with CR inhibited metastasis to liver, lung, and kidney as detected by bioluminescence imaging and histology. Although DON treatment alone did not reduce the incidence of tumor metastasis to spleen compared to the controls, DON administered together with CR significantly reduced the incidence of metastasis to the spleen, indicating a diet/drug synergy. In addition, the phagocytic capabilities of the VM-M3 tumor cells were enhanced during times of energy stress. This allowed for the digestion of engulfed material to be used in energy production. My data provide proof of concept that metabolic therapies targeting both glucose and glutamine metabolism can manage systemic metastatic cancer. Additionally, due to the phagocytic properties of the VM-M3 cell line also seen in a number of human metastatic cancers, I suggest that a unique therapy targeting metabolism and phagocytosis will be required for effective management of metastatic cancer
Thesis (PhD) — Boston College, 2010
Submitted to: Boston College. Graduate School of Arts and Sciences
Discipline: Biology
2
Oosterhout, Anselmus Gerardus Maria van. "Small cell lung cancer and brain metastasis." Maastricht : Maastricht : Rijksuniversiteit Limburg ; University Library, Maastricht University [Host], 1995. http://arno.unimaas.nl/show.cgi?fid=6643.
Full text
3
Boltman, Taahirah. "Liposomal drug delivery to brain cancer cells." University of the Western Cape, 2015. http://hdl.handle.net/11394/4706.
Full textAbstract:
Master of Science (Nanoscience)Neuroblastomas (NBs) are the most common solid extra-cranial tumours diagnosed in childhood and characterized by a high risk of tumour relapse. Like in other tumour types, there are major concerns about the specificity and safety of available drugs used for the treatment of NBs, especially because of potential damage to the developing brain. Many plant-derived bioactive compounds have proved effective for cancer treatment but are not delivered to tumour sites in sufficient amounts due to compromised tumour vasculature characterized by leaky capillary walls. Betulinic acid (BetA) is one such naturally-occurring anti-tumour compound with minimum to no cytotoxic effects in healthy cells and rodents. BetA is however insoluble in water and most aqueous solutions, thereby limiting its therapeutic potential as a pharmaceutical product. Liposomes are self-assembling closed colloidal structures composed of one or more concentric lipid bilayers surrounding a central aqueous core. The unique ability of liposomes to entrap hydrophilic molecules into the core and hydrophobic molecules into the bilayers renders them attractive for drug delivery systems. Cyclodextrins (CDs) are non-reducing cyclic oligosaccharides which proximate a truncated core, with features of a hydrophophilic outer surface and hydrophobic inner cavity for forming host-guest inclusion complexes with poorly water soluble molecules. CDs and liposomes have recently gained interest as novel drug delivery vehicles by allowing lipophilic/non-polar molecules into the aqueous core of liposomes, hence improving the therapeutic load, bioavailability and efficacy of many poorly water-soluble drugs. The aim of the study was to develop nano-drug delivery systems for BetA in order to treat human neuroblastoma (NB) cancer cell lines. This was achieved through the preparation of BetA liposomes (BetAL) and improving the percent entrapment efficiency (% EE) of BetA in liposomes through double entrapment of BetA and gamma cyclodextrin BetA inclusion complex (γ-CD-BetA) into liposomes (γ-CD-BetAL). We hypothesized that the γ-CD-BetAL would produce an increased % EE compared to BetAL, hence higher cytotoxic effects. Empty liposomes (EL), BetAL and γ-CD-BetAL were synthesized using the thin film hydration method followed by manual extrusion. Spectroscopic and electron microscopic characterization of these liposome formulations showed size distributions of 1-4 μm (before extrusion) and less than 200 nm (after extrusion). As the liposome size decreased, the zeta-potential (measurement of liposome stability) decreased contributing to a less stable liposomal formulation. Low starting BetA concentrations were found to be more effective in entrapping higher amounts of BetA in liposomes while the incorporation of γ-CD-BetA into liposomes enhanced the % EE when compared to BetAL, although this was not statistically significant. Cell viability studies using the WST-1 assay showed a time-and concentration-dependent decrease in SK-N-BE(2) and Kelly NB cell lines exposed to free BetA, BetAL and γ-CD-BetAL at concentrations of 5-20 ug/ml for 24, 48 and 72 hours treatment durations. The observed cytotoxicity of liposomes was dependant on the % EE of BetA. The γ-CD-BetAL was more effective in reducing cell viability in SK-N-BE(2) cells than BetAL whereas BetAL was more effective in KELLY cells at 48-72 hours. Exposure of all cells to EL showed no toxicity while free BetA was more effective overall than the respective liposomal formulations. The estimated IC₅₀ values following exposure to free BetA and BetAL were similar and both showed remarkable statistically significant decrease in NB cell viability, thus providing a basis for new hope in the effective treatment of NBs.
4
Isham, L. "Quality of life in paediatric brain cancer." Thesis, University College London (University of London), 2006. http://discovery.ucl.ac.uk/1445605/.
Full textAbstract:
This paper reviews the recent literature on quality of life (QOL) in survivors of paediatric brain tumours. QOL is defined as comprising three domains (physical, emotional and social), and studies investigating single or multiple domains are included. A psychological perspective is taken on QOL whereby it is the degree to which circumstances relating to these domains are distressing or problematic for the individual that is considered key, rather than the circumstances themselves. A total of 23 studies are reviewed and findings are presented in terms of overall QOL, physical QOL, emotional QOL and social QOL. Overall, paediatric brain-tumour survivors appear to be at risk of reduced QOL both when compared to population norms and to other paediatric cancer-populations. Possible risk factors are discussed but fiirther research is needed before definitive conclusions can be reached. Methodological limitations observed in the literature are considered and directions for future research are proposed. In particular, the need for more theory-driven studies is highlighted.
5
Kiebish, Michael Andrew. "Mitochondrial lipidome and genome alterations in mouse brain and experimental brain tumors." Thesis, Boston College, 2008. http://hdl.handle.net/2345/27.
Full textAbstract:
Thesis advisor: Thomas N. SeyfriedMitochondria are the key regulators of the bioenergetic state of the cell. Damage to mitochondrial protein, DNA, or membrane lipids can result as the cause or affect of disease pathology. Regardless, this damage can impair mitochondrial function resulting in a decreased ability to produce ATP to support cellular viability. This thesis research examined the mitochondrial lipidome by shotgun lipidomics in different populations of C57BL/6J (B6) brain mitochondria (non-synaptic and synaptic) and correlated lipid changes to differences in electron transport chain (ETC) activities. Furthermore, a comparison was made for non-synaptic mitochondria between the B6 and the VM mouse strain. The VM strain has a 1.5% incidence of spontaneous brain tumors, which is 210 fold greater than the B6 strain. I determined that differences in the brain mitochondrial lipidome existed in the VM strain compared to the B6 strain, likely corresponding to an increased rate of spontaneous brain tumor formation. Analysis of the mitochondrial genome in the CT-2A, EPEN, VM-NM1, and VM-M3 brain tumors compared to their syngeneic controls mouse strains, C57BL/6J (B6) and VM mice, was examined to determine if mutations existed in experimental brain cancer models. No pathogenic mtDNA mutations were discovered that would likely cause a decrease in the mitochondrial functionality. A novel hypothesis was devised to examine the tumor mitochondrial lipidome to determine if quantitative or molecular species differences existed that could potentially alter the functionality of the ETC. Brain tumor mitochondria were examined from tumors grown in vivo as well as in vitro. Numerous lipid differences were found in the mitochondria of brain tumors, of which the most interesting involved the unique molecular speciation of cardiolipin. ETC activities were significantly decreased in the primary ETC complexes which contribute protons to the gradient as well as the linked complexes of brain tumor mitochondria compared to controls. Taken together, it is likely that differences in the mitochondrial lipidome of brain tumors results in severe impairment of the mitochondria’s ability to produce ATP through the ETC. This research has provided a new understanding of the role of mitochondrial lipids in brain as well as brain cancer and offers an alternative explanation for metabolic dysfunction in cancer
Thesis (PhD) — Boston College, 2008
Submitted to: Boston College. Graduate School of Arts and Sciences
Discipline: Biology
6
Rivera, Maricruz. "MOLECULAR MECHANISMS OF STRESS RESPONSE IN BRAIN CANCER." Case Western Reserve University School of Graduate Studies / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=case1445956088.
Full text
7
Dudley, Alix. "DRR regulates the activation of AKT kinase in brain cancer." Thesis, McGill University, 2012. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=110452.
Full textAbstract:
Brain cancer invasion is a leading cause of treatment failure yet there are no therapies to prevent invasion. In developing therapeutic strategies, we must first identify the molecular mechanisms that regulate this event. We previously identified downregulated in renal cell carcinoma (DRR) as a promoter of invasion that augments focal adhesion turnover in malignant glial cells. We continued to investigate the molecular mechanisms that underlie this invasion by examining cell signaling in the context of DRR. We found that AKT phosphorylation (Ser473, Thr308) is elevated in DRR-over-expressing cells compared to control. Through a series of molecular and pharmacologic techniques, we selectively targeted AKT inputs in order to identify how DRR regulates its activation. We demonstrated that phospho-AKT is recruited to focal adhesions and is activated in an adhesion, SRC-family kinase (SFK), phosphoinositide-3-kinase (PI3K)-dependent and epidermal growth factor receptor (EGFR)-independent manner. We concluded our work by testing the relevance of our model in a 3D invasion assay. Our results demonstrated that SFK but not EGFR inhibition significantly prevents DRR-induced invasion. Together, these findings support a model by which DRR regulates AKT activity to drive malignant glial cell invasion.L'invasion des cellules cancéreuses est la principale cause d'échec des traitements des gliomes car il n'existe actuellement aucune thérapie permettant de bloquer ce processus. Afin de développer des stratégies thérapeutiques efficaces, il apparaît donc essentiel d'identifier les mécanismes moléculaires régulant la migration de ces cellules. Nous avons précédemment montré que la protéine 'downregulated in renal cell carcinoma' (DRR) contribue à l'invasion des cellules gliales malignes en augmentant le renouvellement de leurs complexes d'adhésion focaux. Nous avons poursuivi cette étude par l'analyse des voies de signalisation impliquées dans ce processus et nous avons tout d'abord mis en évidence une augmentation de la phosphorylation d'AKT (Ser473, Thr308) dans les cellules surexprimant DRR. Par une combinaison d'approches moléculaires et pharmacologiques, nous avons alors étudié spécifiquement le rôle de DRR dans l'activation d'AKT et avons démontré que la forme phosphorylée d'AKT est localisée au sein des complexes d'adhésion focaux. Nous avons également mis en évidence que son activation est régulée par SRC, membre de la famille des protéines tyrosine kinase (PTK), et par phosphatidylinositol-3-kinase (PI3K), indépendamment du récepteur à l'EGF. Enfin, nous avons validé notre modèle dans un système d'invasion en trois dimensions ou nous avons montré que l'inhibition spécifique de SRC bloque significativement l'invasion des cellules induite par DRR.L'ensemble de ces résultats nous permet finalement de proposer un modèle selon lequel l'invasion des cellules malignes gliales est régulée par l'activation de la protéine AKT par DRR.
8
Walker, William Harry II. "Effects of Breast Cancer and Chemotherapy on Brain and Behavior." The Ohio State University, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=osu1541942974196214.
Full text
9
Paglia, Simona <1989>. "Development and characterisation of a neurogenic model of brain cancer." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2021. http://amsdottorato.unibo.it/9936/2/Simona%20Paglia%20PhD%20thesis.pdf.
Full textAbstract:
Primary glioblastoma (GB), the most common and aggressive adult brain tumour, is refractory to conventional therapies and characterised by poor prognosis. GB displays striking cellular heterogeneity, with a sub-population, called Glioblastoma Stem Cells (GSCs), intrinsically resistant to therapy, hence the high rate of recurrence. Alterations of the tumour suppressor gene PTEN are prevalent in primary GBM, resulting in the inhibition of the polarity protein Lgl1 due to aPKC hyperactivation. Dysregulation of this molecular axis is one of the mechanisms involved in GSC maintenance.
After demonstrating that the PTEN/aPKC/Lgl axis is conserved in Drosophila, I deregulated it in different cells populations of the nervous system in order to individuate the cells at the root of neurogenic brain cancers. This analysis identified the type II neuroblasts (NBs) as the most sensitive to alterations of this molecular axis. Type II NBs are a sub-population of Drosophila stem cells displaying a lineage similar to that of the mammalian neural stem cells. Following aPKC activation in these stem cells, I obtained an adult brain cancer model in Drosophila that summarises many phenotypic traits of human brain tumours. Fly tumours are indeed characterised by accumulation of highly proliferative immature cells and keep growing in the adult leading the affected animals to premature death.
With the aim to understand the role of cell polarity disruption in this tumorigenic process I carried out a molecular characterisation and transcriptome analysis of brain cancers from our fly model.
In summary, the model I built and partially characterised in this thesis work may help deepen our knowledge on human brain cancers by investigating many different aspects of this complicate disease.
10
Khong, Pek-Lan. "Diffusion tensor MR imaging in the evaluation of treatment-induced white matter injury in childhood cancer survivors." Click to view the E-thesis via HKUTO, 2006. http://sunzi.lib.hku.hk/hkuto/record/B38320666.
Full text
11
Siesjö, Peter. "Immunotherapy of rat brain tumors with mutagen induced, cross-reactive tumor cell variants." Lund : Section of Tumor Immunology, Dept. of Cell and Molecular Biology, University of Lund, 1997. http://books.google.com/books?id=TXZrAAAAMAAJ.
Full text
12
Khoo, Vincent. "A study of conformal radiotherapy methods for brain and prostate cancer." Thesis, Institute of Cancer Research (University Of London), 2000. http://publications.icr.ac.uk/9718/.
Full textAbstract:
State-of-the-art radiotherapy involves a technology chain that includes 3D tumour imaging, 3D treatment planning, treatment delivery using conformal or intensity modulated techniques, and treatment verification. This thesis evaluates some of the recent imaging and planning developments to assess their role in optimisation of the technology chain for brain and prostate cancer. I focused on two major links in this technology chain. The 'imaging' link compared the use of MRI and CT in localising target volumes. An image registration protocol was developed to combine CT and MRI images in the brain. For the localisation of skull base meningiomas, MRI was found to provide contrasting information to CT. A composite target volume derived from both CT and MR information provided the most appropriate volume. For prostate radiotherapy, four MRI sequences were compared to CT. All MRI sequences provided improved localisation of relevant radiotherapy volumes-of-interest especially for the prostatic apex and rectum. The 'treatment planning' link investigated the impact of intra-fraction prostate motion for prostate planning margins, the creation of planning margins, the optimisation of beam orientations for prostate radiotherapy, and the utility of IMRT methods for brain tumours. Cine MR demonstrated a significant relationship between moderate rectal distension and increased rectal activity resulting in prostate motion. Mean prostate motion was < 5mm and lasted < 5% of a7 minute period indicating that the current 10mm prostate planning margin was adequate. The use of a 3D margin-growing method allowed the planning target margin to be accurately realised in all spatial orientations and avoided problems associated with 2D margin growing methods. A variety of co-planar arrangements using 3-, 4-, and 6-fields were evaluated for conformal prostate radiotherapy. Standard prostate plans could be optimised by proper consideration of beam orientations. A 3-field plan with gantry angles of 0", 90', 270' Provided the best rectal sparing for both prostate alone and prostate plus seminal vesicles volumes. Using this 3-field plan, dose escalation may be achieved with a smaller increase in predicted late rectal complications than with other 3-, 4-, or 6-field plans. An IMRT tomotherapy method was compared with conformal radiotherapy for convex shaped brain tumours to assess its potential for improved dose conformation. This IMRT method provided slightly improved PTV coverage but also higher OARs doses. However, these OARs doses remained within acceptable clinical limits. This IMRT tomotherapy method did not provide significant planning improvement compared to current conformal radiotherapy technique.
13
Lowry, Carolyne Mary. "Alterations of the epigenome in brain cancer: loss of 5-hydroxymethylcytosine." Mémoire, Université de Sherbrooke, 2017. http://hdl.handle.net/11143/9864.
Full textAbstract:
Abstract : 5-Methylcytosine is an epigenetic mark, which can be oxidized to 5-hydroxymethylcytosine (5hmC) in DNA by ten-eleven translocation (TET) oxygenases. It is an initial step in the demethylation of 5mC. Levels of 5hmC is relatively high in the brain compared to other organs, but these levels are known to be significantly reduced during the development of a brain tumor, especially in glioblastoma multiforme (GBM). However, no known mechanisms may fully explain this abnormality. The objectives of my project were to (1) understand the implications of the demethylation pathway mediated by TET, and (2) gain a deeper insight in the epigenetic make-up of brain tumors. (1) U87 cells were incubated with 5mC, 5hmC, 5-formylcytosine (5fC) or co-incubated of 5hmC with 3,4,5,6-tetrahydro-2’-deoxyuridine (dTHU) over a timeline of 0, 24, 48 and 96 hours. (2) 130 brain tumors (GBM= 79; grade II/III= 51) were obtained directly from surgery and immediately suspended in DNA extraction buffer. Both cell samples and tumor tissues underwent DNA extraction and DNA digestion protocols. The percent per cytosine (%/C) was obtained by quantification of 5mC, 5hmC, 5fC, 5-hydroxymethyluracil (5hmU) and 5formyluracil (5fU) using LC-MS/MS. (1) Cellular incubations showed that it is possible to increase levels of 5hmC in DNA, but also a slight increase in 5mC levels throughout the experiment. 5HmC levels dramatically increased by 1.9-fold after 96h. On the other hand, no increase was observed in 5fC levels. Both 5hmC and 5fC incubations were accompanied by high increases in 5hmU and 5fU levels respectively. The addition of dTHU to the 5hmC incubation decreased 5hmU incorporation by 65%. (2) The average levels of 5mC, 5hmC and 5fC, in brain tumors, were 4.0, 0.15 and 0.021 %/C respectively. 5HmU and 5fU levels were present at comparable levels of 5hmC and 5fC. Levels of 5hmC, 5hmU and 5fU were significantly lower in the DNA of GBM specimens. There was a strong correlation between 5mC with 5hmC and 5fC in GBM, but this was absent in low grade tumors. The presence of 5hmU and 5fU in brain tumor and the increase in their levels during cell incubations indicate a deamination activity in these cancerous cells, which may impinge on the cellular levels of 5hmC, in particular. Furthermore, upon the incubations with 5hmC, downstream levels of 5fC did not increase suggesting a TET malfunction. TET activity is maintained in GBMs, but impaired in low grade tumors due to isocitrate dehydrogenase-1 (IDH1) mutations. Therefore, in brain tumors, a strong deamination activity and TET impairment may lead to epigenetic reduction of 5hmC.Résumé : 5Mtéthylcytosine (5mC) est une marque épigénétique qui peut être oxydée en 5-hydroxyméthylcytosine (5hmC) par ten-eleven translocation (TET) oxygénases. Ceci amène à l’étape initiale de la déméthylation de 5mC. Le niveau de 5hmC est plus élevé dans le cerveau par rapport aux autres organes. Par contre, ce niveau a une réduction marquante au cours du développement d’une tumeur cérébrale, notamment le glioblastome multiforme (GBM). Toutefois, il n’y a aucun mécanisme connu pour expliquer cette anomalie. Les objectifs de ce projet étaient de (1) discerner l’implication de la voie de déméthylation obtenu par médiation de TET et (2) d’avoir une compréhension plus profonde de la constitution épigénétique des tumeurs cérébraux. (1) Des cellules U87 ont été incubées avec 5mC, 5hmC, 5-fomylcytosine (5fC) et une co-incubation de 5hmC avec 3,4,5,6-tétrahydro-2’-déoxyuridine (dTHU). Les échantillons ont été récoltés à 0, 24, 48, 96 heures. (2) 130 tumeurs cérébraux (GBM = 79; grade II/III = 51) étaient obtenus directement de chirurgie et mise en suspension dans un tampon d’extraction d’ADN le jour même. Les échantillons d’U87 et de tissu tumoral ont subi les protocoles d’extraction et de digestion d’ADN. Le pourcentage par cytosine (%/C) était calculé par la quantification de 5mC, 5hmC, 5fC, 5-hydroxyméthyluracile (5hmU) et 5-formyluracile (5fU) en utilisant LC-MS/MS. (1) Les incubations d’U87 ont démontrées la possibilité augmenter les niveaux génomique de 5hmC, mais aussi une légère augmentation des niveaux de 5mC. Les niveaux de 5hmC ont accru de 1.9 fois après 96hrs. Par contre, aucune variation n’a été observée dans les niveaux de 5fC. Les incubations de 5hmC et 5fC ont été accompagnées par une élévation des niveaux de 5hmU et 5fU respectivement. L’addition de dTHU avec 5hmC avait diminué l’incorporation de 5hmU par 65%. (2) Dans les tumeurs cérébraux, les niveaux moyens de 5mC, 5hmC et 5fC étaient de 4.0, 0.15 et 0.021%/C respectivement. Les quantités de 5hmU et 5fU étaient grandement plus faible dans le GBMs que dans les tumeurs de bas grades. La présence de 5hmU et 5fU dans les tumeurs et leur augmentation durant l’incubation des U87 indiquent une activité de désamination, qui peut, en particulier, entraver les niveaux de 5hmC. En outre, malgré l’incubation avec 5mC, les niveaux de 5hmC et 5fC n’ont pas augmentés suggérant un dysfonctionnement de TET. L’activité de TET est maintenue dans GBM, mais altérée dans les tumeurs de bas grades à cause de mutation isocitrate dehydrogenase-1 (IDH1). Par conséquent, la forte activité de désamination et la déficience en TET peuvent conduire à une réduction épigénétique.
14
Maxwell, Marius. "Expression of proto-oncogenes and growth factors in glioblastoma multiforme." Thesis, University of Oxford, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.259967.
Full text
15
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.
Full text
16
Fortin, Ensign Shannon Patricia. "THE TWEAK-FN14 LIGAND RECEPTOR AXIS PROMOTES GLIOBLASTOMA CELL INVASION AND SURVIVAL VIA ACTIVATION OF MULTIPLE GEF-RHO GTPASE SIGNALING SYSTEMS." Thesis, The University of Arizona, 2015. http://hdl.handle.net/10150/528171.
Full textAbstract:
A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine.Glioblastoma (GB) is the highest grade and most common form of primary adult brain tumors, characterized by a highly invasive cell population. GB tumors develop treatment resistance and ultimately recur; the median survival is nearly fifteen months and importantly, the invading cell population is attributed with having a decreased sensitivity to therapeutics. Thus, there remains a necessity to identify the genetic and signaling mechanisms that promote tumor spread and therapeutic resistance in order to develop new targeted treatment strategies to combat this rapidly progressive disease. TWEAK-Fn14 ligand-receptor signaling is one mechanism in GB that promotes cell invasiveness and survival, and is dependent upon the activity of multiple Rho GTPases including Rac1. Here, we show that Cdc42 is essential in Fn14-mediated Rac1 activation. We identified two guanine nucleotide exchange factors (GEFs), Ect2 and Trio, involved in the TWEAK-induced activation of Cdc42 and Rac1, respectively, as well as in the subsequent TWEAK-Fn14 directed glioma cell migration and invasion. In addition, we characterized the role of SGEF in promoting Fn14-induced Rac1 activation. SGEF, a RhoG-specific GEF, is overexpressed in GB tumors and promotes TWEAK- Fn14-mediated glioma invasion. Moreover, we characterized the correlation between SGEF expression and TMZ resistance, and defined a role for SGEF in promoting the survival of glioma cells. SGEF mRNA and protein expression are regulated by the TWEAK-Fn14 signaling axis in an NF-B dependent manner and inhibition of SGEF expression sensitizes glioma cells to TMZ treatment. Lastly, gene expression analysis of SGEF depleted GB cells revealed altered expression of a network of DNA repair and survival genes. Thus TWEAK-Fn14 signaling through the GEF-Rho GTPase systems which include the Ect2, Trio, and SGEF activation of Cdc42 and/or Rac1 presents a pathway of attractive drug targets in glioma therapy, and SGEF signaling represents a novel target in the setting of TMZ refractory, invasive GB cells.
17
Mannino, Mariella. "Improving treatment of glioblastoma : new insights in targeting cancer stem cells effectively." Thesis, University of Sussex, 2015. http://sro.sussex.ac.uk/id/eprint/58695/.
Full textAbstract:
Glioblastoma is the most common primary malignant brain tumour in the adult population. Despite multimodality treatment with surgery, radiotherapy and chemotherapy, outcomes are very poor, with less than 15% of patients alive after two years. Increasing evidence suggests that glioblastoma stem cells (GSCs) are likely to play an important role in the biology of this disease and are involved in treatment resistance and tumour recurrence following standard therapy. My thesis aims to address two main aspects of this research area: 1) optimization of methods to evaluate treatment responses of GSCs and their differentiated counterparts (non-GSCs), with a particular focus on a tissue culture model that resembles more closely the tumoral niche; 2) characterization of cell division and centrosome cycle of GSCs, investigating possible differences between these cells and non-GSCs, that would allow the identification of targets for new therapeutic strategies against glioblastomas. In the first part of my project, I optimized a clonogenic survival assay, to compare sensitivity of GSCs and non-GSCs to various treatments, and I developed the use of a 3-dimentional tissue culture system, that allows analysis of features and radiation responses of these two subpopulations in the presence of specific microenvironmental factors from the tumoral niche. In the second part, I show that GSCs display mitotic spindle abnormalities more frequently than non-GSCs and that they have distinctive features with regards to the centrosome cycle. I also demonstrate that GSCs are more sensitive than non-GSCs to subtle changes in Aurora kinase A activity, which result in a rapid increase in polyploidy and subsequently in senescence, with a consistent reduction in clonogenic survival. Based on these findings, I propose that kinases involved in the centrosome cycle need to be explored as a novel strategy to target GSCs effectively and improve outcomes of glioblastoma patients.
18
Katz, Yarden. "Functional and computational analysis of RNA-binding proteins and their roles in cancer." Thesis, Massachusetts Institute of Technology, 2014. http://hdl.handle.net/1721.1/89864.
Full textAbstract:
Thesis: Ph. D., Massachusetts Institute of Technology, Department of Brain and Cognitive Sciences, 2014.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
Cataloged from student-submitted PDF version of thesis.
Includes bibliographical references (pages 197-200).
This work is concerned with mRNA processing in mammalian cells and proceeds in two parts. In the first part, I introduce a computational framework for inferring the abundances of mRNA isoforms using high-throughput RNA sequencing data. This framework was applied to study the targets of the ubiquitous splicing factor hnRNP H in human cells. In the second part, I describe an experimental study of the Musashi (hnRNP-like) family of RNA-binding proteins in stem cells and cancer cells, which incorporates computational analyses that rely heavily on the framework developed in part one. In sum, this work provides a computational framework of general use in global analyses of RNA processing and its protein regulators, as well as functional insights into a family of poorly understood RNA-binding proteins. Several related analyses and techniques developed as part of the thesis are described in Appendix A-C. Appendix A describes a study of activity-dependent gene expression and mRNA processing in the mouse olfactory bulb. It uses computational techniques developed in part one of the thesis. Appendix B describes a technique for quantitative visualization of alternative splicing from RNA sequencing data and its integration into a genome browser. Appendix C describes a method for clonal analysis of neural stem cell growth and differentiation in culture using live imaging and `microdot' plates, developed as part of the work presented in part one of the thesis.
by Yarden Katz.
Ph. D.
19
Punjaruk, Wiyada. "The contribution of drug resistant cancer stem cells to paediatric brain tumours." Thesis, University of Nottingham, 2010. http://eprints.nottingham.ac.uk/13403/.
Full textAbstract:
Introduction: Recent studies have revealed that cancer stem cells (CSCs) exist in malignant disease. Additionally, it is proposed that these cells may survive following chemotherapy, and hence contribute to tumour relapse. A significant mechanism of drug resistance in CSCs is believed to be the expression of ATP-binding cassette (ABC) transporters that efflux cytotoxic agents out of cells. The objective of this study was to study the existence of CSCs in a panel of primary paediatric brain tumours (PBTs) and to determine if these were drug resistant via functional ABC transporters. Materials and Methods: The main cell lines characterised were: EPN-2 (primary ependymoma); MED-2 (recurrent medulloblastoma); SPNET-1 [primary CNS primitive neuroectodermal tumour (CNS PNET)]; and a commercial CNS PNET (PFSK-1). Basic characterisation of our cell lines were assessed by Telomeric Repeat Amplification Protocol (TRAP) assay, Terminal Restriction Fragments (TRF) assay, metaphase spread analysis and doubling time. To determine the proportion of cancer stem-like cells in the parental cell lines, CD133 and SOX2 co-staining immunofluorescence was performed and validated by Western blotting analysis. The expression of ABC transporters (ABCB1, ABCC1 and ABCG2) was also investigated by co-staining for CD133 and ABC transporters using immunofluorescence and Western blotting analysis. Flow cytometry was performed to examine ABCB1 function. Four clinically relevant drugs (etoposide, cisplatin, irinotecan and methotrexate) were used to assess the degree of drug resistance of these lines. Clonnogenic assay and neurosphere formation assay were then performed to investigate colony survival and the ability of cells to form neurospheres, respectively, after drug treatment. Finally, the potential to increase chemosensitivity by drug treatment in the presence of the ABCB1 inhibitor, Verapamil, was assessed. Results: Basic characterisation results demonstrated that a high level of telomerase activity and maintenance of telomere length was found in all cell lines (grown both as monolayers and neurospheres). Metaphase spread analysis showed a wide range of aberrant chromosome numbers in PFSK-1 cells whereas our cell lines demonstrated a more stable chromosome number. Neurospheres grew slower than monolayers and monolayers had constant growth rate with increasing passage number. It was found that for each cell line, a small subpopulation (8-12%) of cultured monolayer cells are positive for both CD133 and SOX-2 immunofluorescent staining whilst cultured neurospheres contained 35-45% of co-stained cells. No co-stained cells were identified in the commercial PFSK-1 line and these findings were consistent with the results from Western blotting analysis. Approximately 10% of the parental cell lines comprised cells co-expressing CD133 and ABCB1 or ABCC1 at a low level whilst none of our cell lines were positive for ABCG2. Additionally, the parental cell lines contained a small proportion of cells expressing functional endogenous ABCB1 (34±5.2% in EPN-2, 26.5±3.9% in MED-2 and 13.9±3.2% in SPNET-1). During multiple rounds of drug treatment, ABCB1 was consistently expressed at a high level throughout and the proportion of functional ABCB1 expressing cells increased in all cell lines almost 2 fold compared to the parental cell lines and the selected control sublines. Whilst ABCC1 expression was gradually upregulated after multiple rounds of treatment but ABCG2 expression remained negative. Drug combined with Verapamil treatment significantly decrease survival rate approximately 5 fold compared to drug treatment alone although the majority of surviving cells were still CD133 and ABCB1 positive. Conclusion: Newly established paediatric cell lines (EPN-2, MED-2 and SPNET-1) represented significant histological and biological features of the original tumours from which they were derived and were stable in standard culture condition for a prolonged period of time. The parental cell lines contained a small proportion of cells expressing endogenous functional ABCB1 at a low level indicating intrinsic drug resistance. After multiple rounds of drug treatment, ABCB1 was the major mechanism of drug resistance in our cell lines. ABCC1 were upregulated later in our cell lines after multiple rounds of drug treatment whereas none of our cell lines expressed ABCG2 during drug treatment.
20
Jagannathan, Rupa. "A case-based reasoning system for radiotherapy treatment planning for brain cancer." Thesis, University of Nottingham, 2013. http://eprints.nottingham.ac.uk/29318/.
Full textAbstract:
In this thesis, a novel case-based reasoning (CBR) approach to radiotherapy treatment planning for brain cancer patients is presented. In radiotherapy, tumour cells are destroyed using ionizing radiation. For each patient, a treatment plan is generated that describes how the radiation should be applied in order to deliver a tumouricidal radiation dose while avoiding irradiation of healthy tissue and organs at risk in the vicinity of the tumour. The traditional, manual trial and error approach is a time-consuming process that depends on the experience and intuitive knowledge of medical physicists. CBR is an artificial intelligence methodology, which attempts to solve new problems based on the solutions of previously solved similar problems. In this research work, CBR is used to generate the parameters of a treatment plan by capturing the subjective and intuitive knowledge of expert medical physicists stored intrinsically in the treatment plans of similar patients treated in the past. This work focusses on the retrieval stage of the CBR system, in which given a new patient case, the most similar case in the archived case base is retrieved along with its treatment plan. A number of research issues that arise from using CBR for radiotherapy treatment planning for brain cancer are addressed. Different approaches to similarity calculation between cases are investigated and compared, in particular, the weighted nearest neighbour similarity measure and a novel non-linear, fuzzy similarity measure designed for our CBR system. A local case attribute weighting scheme has been developed that uses rules to assign attribute weights based on the values of the attributes in the new case and is compared to global attribute weighting, where the attribute weights remain constant for all target cases. A multi-phase case retrieval approach is introduced in which each phase considers one part of the solution. In addition, a framework developed for the imputation of missing values in the case base is described. The research was carried out in collaboration with medical physicists at the Nottingham University Hospitals NHS Trust, City Hospital Campus, UK. The performance of the developed methodologies was tested using brain cancer patient cases obtained from the City Hospital. The results obtained show that the success rate of the retrieval mechanism provides a good starting point for adaptation, the next phase in development for the CBR system. The developed automated CBR system will assist medical physicists in quickly generating treatment plans and can also serve as a teaching and training aid for junior, inexperienced medical physicists. In addition, the developed methods are generic in nature and can be adapted to be used in other CBR or intelligent decision support systems for other complex, real world, problem domains that highly depend on subjective and intuitive knowledge.
21
Marsili, Stefania. "Interplay between JCV Large T-antigen and Cullin-7 in Brain Cancer." Diss., Temple University Libraries, 2011. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/132768.
Full textAbstract:
BiologyPh.D.
A convincing body of evidence suggests that ubiquitination and the ubiquitin proteasome degradation pathway play a key role in neoplastic transformation. Ubiquitination, as post-translation modification, is involved both in functional regulation and degradation of specific cellular targets known as proto-oncogenes and tumor suppressors. Oncogenic viral proteins interact both with proto-oncoproteins and tumor suppressors leading to the modulation of their cellular function by several mechanisms including ubiquitination. Interestingly, viral oncoproteins themselves can also be regulated by this post-translation modification. Additionally, viruses can assemble their own E3 ligases or regulate the activity of cellular E3 ligases. E3 ligases, involved in the final step of the ubiquitination process, are the enzymes that provide the specificity for the interaction with target substrates by the means of a large number of proteins. Recent studies on the potential correlation between viral infection and oncogenesis, have addressed the emerging role of the ubiquitination system as a possible mediator for cancer transformation. In this scenario we hypothesized that JCV T-antigen may interfere with the ubiquitination system and we investigated a possible interaction between JCV T-antigen and the E3 ligase Cul7. To prove our hypothesis we performed co-immunoprecipitation and co-immunofluorescence experiments using the glioblastoma cell lines HJC12, U87MG and HJC5. Our results indicate that JCV T-antigen and Cul7 interact in the cytoplasmic compartment. In addition, JCV T-antigen stabilizes Cul7. These observations suggest that JCV T-antigen can modulate Cul7 E3 ligase activity leading to oncogenesis. Further study addressing the biological significance of this interaction will decipher the cellular processes modulated by JCV T-antigen and Cul7 and will indicate new avenues for therapeutic intervention.
Temple University--Theses
22
Cheng, Kun. "Deformable models for adaptive radiotherapy planning." Thesis, University of Edinburgh, 2016. http://hdl.handle.net/1842/22893.
Full textAbstract:
Radiotherapy is the most widely used treatment for cancer, with 4 out of 10 cancer patients receiving radiotherapy as part of their treatment. The delineation of gross tumour volume (GTV) is crucial in the treatment of radiotherapy. An automatic contouring system would be beneficial in radiotherapy planning in order to generate objective, accurate and reproducible GTV contours. Image guided radiotherapy (IGRT) acquires patient images just before treatment delivery to allow any necessary positional correction. Consequently, real-time contouring system provides an opportunity to adopt radiotherapy on the treatment day. In this thesis, freely deformable models (FDM) and shape constrained deformable models (SCDMs) were used to automatically delineate the GTV for brain cancer and prostate cancer. Level set method (LSM) is a typical FDM which was used to contour glioma on brain MRI. A series of low level image segmentation methodologies are cascaded to form a case-wise fully automatic initialisation pipeline for the level set function. Dice similarity coefficients (DSCs) were used to evaluate the contours. Results shown a good agreement between clinical contours and LSM contours, in 93% of cases the DSCs was found to be between 60% and 80%. The second significant contribution is a novel development to the active shape model (ASM), a profile feature was selected from pre-computed texture features by minimising the Mahalanobis distance (MD) to obtain the most distinct feature for each landmark, instead of conventional image intensity. A new group-wise registration scheme was applied to solve the correspondence definition within the training data. This ASM model was used to delineated prostate GTV on CT. DSCs for this case was found between 0.75 and 0.91 with the mean DSC 0.81. The last contribution is a fully automatic active appearance model (AAM) which captures image appearance near the GTV boundary. The image appearance of inner GTV was discarded to spare the potential disruption caused by brachytherapy seeds or gold markers. This model outperforms conventional AAM at the prostate base and apex region by involving surround organs. The overall mean DSC for this case is 0.85.
23
Gill, Simrandip Kaur. "Single voxel proton magnetic resonance spectroscopy of childhood brain tumours." Thesis, University of Birmingham, 2014. http://etheses.bham.ac.uk//id/eprint/4899/.
Full textAbstract:
Conventional magnetic resonance imaging (MRI) is essential for the management of childhood brain tumours. However, it is increasingly being supplemented with functional techniques such as magnetic resonance spectroscopy (MRS). This thesis investigates how pre-treatment single voxel MRS can aid in diagnosis and surveillance of paediatric brain tumours and identify prognostic biomarkers. Data from multiple centres, scanners from three leading manufacturers and field strengths of 1.5 T and 3 T are incorporated. MRS was analysed using TARQUIN software with metabolite peaks fitted using a simulated basis set to provide metabolite concentrations. Univariate and multivariate statistical tests were used to compare variables. Multi-scanner spectroscopy detected significant differences in common and rare paediatric brain tumours. Diagnostic metabolite profiles were able to confirm tumour on follow-up imaging. Elevated creatine and total choline determined good prognosis in medulloblastoma. Myo-inositol and citrate aided in the characterisation of diffuse pontine gliomas (DIPG). While conventional MRI was unable to identify prognostic markers for DIPG, elevated taurine was found to be significantly associated with a better prognosis. The results encourage the use of MRS as an adjunct to conventional MRI in routine clinical practice. For future studies, accurate assignment of biomarkers will be determined in tumour tissue using in vitro high-resolution spectroscopy methods.
24
Neal, Anthony James. "Optimisation of radiotherapy treatment planning for tumours of the breast, prostate and brain." Thesis, King's College London (University of London), 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.306922.
Full text
25
Xing, Fei. "ROLE OF NOTCH SIGNALING IN BREAST CANCER METASTASIS." OpenSIUC, 2012. https://opensiuc.lib.siu.edu/dissertations/514.
Full textAbstract:
Notch signaling is often and aberrantly activated by hypoxia during tumor progression; however, the exact pathological role of hypoxia-induced Notch signaling in tumor metastasis is as yet poorly understood. In the first part of this study, we aimed to define the mechanism of Notch ligand activation by hypoxia in both primary tumor and bone stromal cells in the metastatic niche and to clarify their roles in tumor progression. We have analyzed the expression profiles of various Notch liagnds in 779 breast cancer patients in GEO database and found that the expression of Jagged2 among all five ligands is most significantly correlated with the overall- and metastasis-free survival of breast cancer patients. The results of our immunohistochemical (IHC) analysis for Jagged2 in 61 clinical samples also revealed that both Jagged2 and Notch signaling were strongly up-regulated at the hypoxic invasive front. Activation of Jagged2 by hypoxia in tumor cells induced EMT and also promoted cell survival in vitro. Notably, a ã-secretase inhibitor significantly blocked Notch-mediated invasion and survival under hypoxia by promoting expression of E-cadherin and inhibiting Akt phosphorylation. Importantly, Jagged2 was also found to be up-regulated in bone marrow stroma under hypoxia and promoted the growth of cancer stem-like cells by activating their Notch signaling. Therefore, hypoxia-induced Jagged2 activation in both tumor invasive front and normal bone stroma plays a critical role in tumor progression and metastasis, and Jagged2 is considered to be a valuable prognostic marker and may serve as a novel therapeutic target for metastatic breast cancer. In the second part of this study, the role of Notch signaling in brain metastasis was investigated. Metastatic diseases are responsible for the majority of the deaths in breast cancer patients and the brain is one of the most common metastatic sites. The metastatic tumor in the brain profoundly affects the cognitive and sensory functions as well as morbidity of patients, and the one year survival rate among these patients remains less than 20%. However, the pathological mechanism of brain metastasis is as yet poorly understood. In this report, we found that metastatic breast tumor cells in the brain highly expressed IL-1â which can "activate" astrocytes. This activation significantly augmented the expression of JAG1 in the reactive astrocytes, which in turn activated Notch signaling pathway of cancer stem-like cells (CSCs) upon direct interaction. We also found that the activated Notch signaling in CSCs up-regulated Sox2 followed by promoting self-renewal of CSCs. Furthermore, we have shown that the blood-brain barrier permeable Notch inhibitor, Compound E, can significantly suppress the brain metastasis growth in our animal model. These results represent a novel paradigm for the understanding of how metastatic breast CSCs re-establish their niche for their self-renewal in a totally different microenvironment, which opens a new avenue to identify a novel and specific target for the brain metastatic disease
26
Schmiegelow, Marianne. "Endocrinological late effects following radiotherapy and chemotherapy of childhood brain tumours. /." København : Lægeforeningens Forlag, 2005. http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&doc_number=014566238&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA.
Full text
27
歐穎嫻 and Wing-han Au. "Brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinaseB (TRKB) signaling in ovarian cancer." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B39557947.
Full text
28
Moyers-Ruiz, Liliana. "Chemo brain and prospective memory in breast cancer patients : a mixed methods study." Thesis, Bournemouth University, 2016. http://eprints.bournemouth.ac.uk/24745/.
Full textAbstract:
Some breast cancer patients report memory deficits after undergoing cancer treatment. This deficit has been given the term chemo brain. Patients who report such deficits usually complain about attention and concentration problems, such as forgetting to take their medication, or taking it twice, forgetting doctor’s appointments, reduced ability to multitask, and difficulties with driving, among others. These difficulties can significantly affect their quality of life. Most of the research to date has focused on examining a global neuropsychological aspect of chemo brain, and in the last decade , attention has been directed to the use of neuroimaging techniques. The major question addressed in this study is whether chemo brain in breast cancer patients specifically a prospective memory deficit, and whether neuropsychological assessment lacks ecological validity to measure chemo brain. It is also suggested that biological factors such as sleep and sleepiness are altered during the course of cancer treatment, and those factors may also be playing a role in the cognitive impairment of cancer patients. The method used to examine these questions included a mixed methods design in which a quantitative study was conducted using a neuropsychological battery and physiological measures as well as a qualitative study, which involved thematic analyses and case studies, aided by semi-structured interviews and questionnaires. Overall, the results of this study confirmed that breast cancer patients have poorer prospective memory than controls, and that patients’ self-reports are inconsistent with results derived from the objective neuropsychological battery. This implies that more sensitive measures for the assessment of chemo brain should be developed, and that more emphasis needs to be placed on the study of prospective memory and chemo brain to provide patients with the most efficient care and psychological treatment in order to improve their quality of life.
29
Wams, Emma J. "Neurodegeneration and brain cancer : a longitudinal field study of rest-activity and sleep." Thesis, University of Oxford, 2012. http://ora.ox.ac.uk/objects/uuid:23d242cd-45c7-4dca-a3c5-b1e83747af13.
Full textAbstract:
This thesis investigates rest-activity and sleep profiles in neurodegeneration and brain cancer. Study 1 comprised longitudinal field assessments of rest-activity, sleep and memory in controls and memory-impairment individuals with: subjective memory complaint (SMC), amnestic mild cognitive impairment (aMCI), mild and moderate Alzheimer’s disease (AD). Four questions were addressed: (1) is SMC a prodromal stage of AD? (2) do characteristics of SMC predict future decline? (3) does cholinergic medication (ChEI) impact rest-activity and sleep of moderate AD patients? and (4) are there factors predicting response to ChEI? Study 2 assessed rest-activity and melatonin rhythms in a brain cancer patient (JJB), and post-mortem analysis of brain tissue assessed infiltration of cancer cells on the circadian clock (SCN). Both studies used questionnaires, cognitive tests, electroencephalography and actigraphy simultaneously at patients’ homes. In Study 1, the SMC group showed a reduced activity amplitude to be correlated with increasing memory impairment severity, lower sleep quality and efficiency. Increased sleep fragmentation was observed in all memory-impaired groups, although not correlated to impairment severity. Increased fragmentation of rest-activity rhythm correlated with increasing memory impairment severity in all groups except SMC. Following ChEI medication with donepezil, moderate AD patients showed increased sleep fragmentation, probably due to potentiation of available acetylcholine known to maintain arousal. Higher daytime-activity and lower activity in the rest-phase, when drug-naïve, predicted improved cognition following ChEIs. In Study 2, cancer cell infiltration of the patient’s SCN was confirmed. However, a robust circadian rest-activity period with a misaligned melatonin phase, was recorded, indicating that the effects of partial SCN lesions in humans are complex and this result was possibly in part are due to the masking effect of social behaviour.
30
Engberg, Jonas. "Deep morphological quantification and clustering of brain cancer cells using phase-contrast imaging." Thesis, Uppsala universitet, Avdelningen för visuell information och interaktion, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-454959.
Full textAbstract:
Glioblastoma Multiforme (GBM) is a very aggressive brain tumour. Previous studies have suggested that the morphological distribution of single GBM cells may hold information about the severity. This study aims to find if there is a potential for automated morphological qualification and clustering of GBM cells and what it shows. In this context, phase-contrast images from 10 different GBMcell cultures were analyzed. To test the hypothesis that morphological differences exist between the cell cultures, images of single GBM cells images were created from an image over the well using CellProfiler and Python. Singlecellimages were passed through multiple different feature extraction models to identify the model showing the most promise for this dataset. The features were then clustered and quantified to see if any differentiation exists between the cell cultures. The results suggest morphological feature differences exist between GBM cell cultures when using automated models. The siamese network managed to construct clusters of cells having very similar morphology. I conclude that the 10 cell cultures seem to have cells with morphological differences. This highlights the importance of future studies to find what these morphological differences imply for the patients' survivability and choice of treatment.
31
Mason, Erica Ellis. "Magnetic particle imaging for intraoperative breast cancer margin assessment and functional brain imaging." Thesis, Massachusetts Institute of Technology, 2020. https://hdl.handle.net/1721.1/128037.
Full textAbstract:
This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Thesis: Ph. D., Harvard-MIT Program in Health Sciences and Technology, 2020
Cataloged from student-submitted PDF version of thesis.
Includes bibliographical references (pages 171-185).
Magnetic Particle Imaging (MPI) is an emerging tracer-based imaging modality that uniquely images the nonlinear magnetization of superparamagnetic iron oxide nanoparticles (SPIOs). MPI boasts high sensitivity, zero background signal, positive contrast, fast temporal resolution, and quantitative detection. The field of MPI is currently preclinical, and this work aims to scale MPI to human sizes by developing and validating it for two clinical applications: tumor detection and imaging for intraoperative margin assessment during breast-conserving surgery (BCS), and functional neuroimaging. For margin assessment in BCS, a hand-held Magnetic Particle detector and a small-bore MPI imager are assessed for intraoperative use along with an injected SPIO agent. The goal is to detect positive margins during surgery and thus reduce the need for future reexcision. Both hardware systems are validated using clinically relevant phantoms. For functional Magnetic Particle Imaging (fMPI) of the brain, a continuous time-series MPI imager is developed and validated for imaging of cerebral blood volume (CBV) changes during functional activation. The goal is improved sensitivity beyond the capabilities of current functional imaging modalities. We present initial results of in vivo rodent fMPI in a small-bore imager, and the design of a human head-sized system, with implementation underway. Through the collective development of these MPI hardware systems and validation of their potential for these two clinical applications, this work aims to catalyze the expansion of MPI into the clinical setting.
by Erica Ellis Mason.
Ph. D.
Ph.D. Harvard-MIT Program in Health Sciences and Technology
32
Williams, Jennifer Nicole. "Metal Containing Nucleosides that Function as Therapeutic and Diagnostic Agents Against Brain Cancer." Cleveland State University / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=csu1409238775.
Full text
33
Bergin, Stephen Michael. "Hypothalamic brain-derived neurotrophic factor regulates lymphocyte immunity, energy balance, and cancer progression." The Ohio State University, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487669797216355.
Full text
34
Sayyad, Megan R. "The role of Syndecan-1 and extracellular vesicles in breast cancer brain metastasis." VCU Scholars Compass, 2019. https://scholarscompass.vcu.edu/etd/5874.
Full textAbstract:
Breast cancer metastasizes to the brain in 15-30% of all breast cancer cases, and metastasis is the predominant cause of breast cancer-related deaths. Patients with HER2-enriched and triple-negative breast cancers (TNBCs) are more likely to develop brain metastases. While targeted therapies exist for HER2-enriched breast cancers, there are no effective treatments for TNBCs. Thus, a greater understanding of how these cancers spread to the brain is critical. In order to spread to the brain, disseminated breast cancer cells must overcome 2 major steps—crossing the blood-brain barrier (BBB) and survival and successful colonization of the distinctive and mostly cellular brain environment. Here, we report a novel role for breast cancer cell surface receptor, Syndecan-1 (Sdc1), a heparan sulfate proteoglycan, in promoting breast cancer cell transmigration across the BBB. We found that when we silenced Sdc1 expression in a highly metastatic TNBC cell line, MDA-MB-231, these cells exhibited reduced migration across an in vitro BBB model system. Further, in an in vivo experimental model of metastasis, mice injected with MDA-MB-231 Sdc1 KD (knock-down) cells developed less brain metastases than mice injected with control non-silencing (NS1) cells. Conversely, we found that overexpression of Sdc1 in a metastatic triple-negative mouse mammary carcinoma cell line, 4T1, led to an increase in brain metastases compared to empty vector control-treated mice. We predicted that a secreted factor(s) facilitated BBB disruption that allowed for Sdc1-mediated BBB transmigration, and found that silencing Sdc1 led to decreases in the production and/or release of various cytokines and chemokines implicated in BBB permeability and transmigration. In addition to supporting BBB transmigration, through an in vitro tissue section adhesion assay, we found that Sdc1 also facilitates adhesion of breast cancer cells to the brain, and not to the liver or lungs, revealing specificity for the brain. Further, we report that Sdc1 is expressed in 81% of breast cancer patient brain metastases in our tissue microarray study and that patients with TNBC and high Sdc1 expression have shorter disease-free survival based on a study performed using data from The Cancer Genome Atlas. Taken together, we predict that breast cancer cell Sdc1-regulated cytokines and chemokines promote BBB permeability and/or support transmigration to facilitate breast cancer metastasis to the brain.
We also provide evidence for breast cancer-secreted extracellular vesicles, namely exosomes, in supporting the formation of a pro-metastatic brain environment. We compared exosomes derived from the metastatic 4T1 mouse mammary carcinoma cell line to a non-metastatic counterpart, the 67NR cell line, to assess their microRNA and protein composition and their effect(s) on recipient astrocytes, known mediators of brain metastasis. We found that there are inherent differences in both the microRNA and protein cargo from the metastatic 4T1 cells compared to the non-metastatic 67NR cells, whereby the metastatic 4T1 cells contained various tumor-promoting microRNAs and proteins, and also contained 4.5-fold more protein than the non-metastatic 67NR cells. Mouse astrocytes treated with the metastatic 4T1 exosomes exhibited a shift towards a pro-metastatic phenotype, characterized by upregulation of pro-inflammatory genes, and genes associated with astrocyte reactivity and cancer, whereby 67NR exosome-treated astrocytes exhibited a response profile that overlapped with untreated controls. Overall, these findings reveal an important role for exosomes in driving changes in the brain microenvironment to create a site conducive for cancer growth. Together, both studies help to elucidate how breast cancer cells can invade and colonize the unique brain environment.
35
Davis, Jonathan. "Cancer risk in children of agricultural health study participants." Diss., University of Iowa, 2017. https://ir.uiowa.edu/etd/5926.
Full textAbstract:
This study examines the risk of cancer in children of pesticide applicators from the Agricultural Health Study. The study includes 36,537 children of Iowa participants who were evaluated for cancer incidence during 1975 through 2013 from birth through the age of seventeen. Standard incidence rates for any cancer and specific groups of cancers classified using the International Classification of Childhood Cancer was calculated using rates from the general population of Iowa controlling for year of follow, age, sex, and race. Hazard ratios for Group I-III cancers and paternal exposure to specific pesticides were calculated using exposure information collected on 50 pesticides during phase 1 and 2 of the Agricultural Health Study. The exposure information allowed for calculation of intensity-weighted days of exposure to pesticides using the Agricultural Health Study exposure algorithm. Additionally, maternal ever exposure to specific pesticides was used to evaluate risk of childhood cancer.
There were 118 cancers identified in children of Agricultural Health Study participants. The all-cancer standardized incidence ratio was significantly elevated (SIR = 1.27 95% CI: 1.04-1.50). The most common groups of cancers were Group I leukemia, myeloproliferative disease, and myelodysplastic disease (n=34) followed by Group III central nervous system (CNS) and miscellaneous intracranial and intraspinal neoplasms (n=25).
For paternal intensity-weighted days of exposure, there were 31 of 50 specific pesticides that had sufficient cases of cancer to investigate using Cox proportional hazard models. The herbicide trifluralin significantly increased the risk for Group I childhood cancers for any parental pesticide exposure 2 years before birth through birth when compared to children with no paternal exposure (HR = 2.72 95% CI: 1.15, 6.44). This was consistent with results found from analyzing exposure split into two quantiles based on median exposure of exposed children with a Group I cancer. Parental use of the herbicide S-Ethyl-dipropylthiocarbamate (EPTC) did not result in a sufficient number of Group III cancer cases to look at levels of exposure to EPTC, but ever exposure showed an increased hazard ratio when compared to children with unexposed fathers (HR = 2.56 95% CI: 1.06, 6.20). Other pesticides (dicamba, cyanazine, and terbufos) showed mixed evidence of an association with specific childhood cancers, but were either under powered to evaluate with sensitivity analysis or showed inconsistent risk across exposure levels. Less extensive exposure information was available for mothers of children of the Agricultural Health Study, so analysis was restricted to ever or never exposure to pesticides during a mother’s lifetime. Additionally, there were a limited number of cases of cancer for which maternal exposure to specific pesticides was reported resulting in only 4 pesticides being evaluated for childhood cancer risk (glyphosate, 2,4-dichlorophenoxyacetic acid (2,4-D), carbaryl, and malathion). For these four pesticides, this study did not detect any increased risk of childhood cancer from maternal exposure.
In summary, this study provides the first epidemiological evidence of an increased risk of childhood cancer for trifluralin and EPTC. Since this study provides the first evidence of this increased risk, additional analysis is needed to validate the results. This study demonstrates how pesticide exposure information from participants of the AHS can be used in the evaluation of their children’s cancer risk. Additional follow-up and analysis of this cohort beyond the age of 17 would provide further insight into cancer risk during early adulthood from early life pesticide exposure.
36
Lee, Derek, and 李揚俊. "MicroRNA-210 and endoplasmic reticulum chaperones in the regulation of chemoresistance in glioma." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2014. http://hdl.handle.net/10722/206606.
Full textAbstract:
Gliomas are the commonest type of primary malignant brain tumours of the central nervous system (CNS). The highly aggressive and infiltrative characteristics of gliomas render them one of the most lethal cancers. Amongst all, the most malignant form of glioma is glioblastoma multiforme (GBM), a World Health Organization (WHO) grade IV astrocytoma. Despite well-developed multimodal treatment including surgery, radiotherapy, and chemotherapy, the prognosis of GBM patients remains poor with median survival of just over one year. This high mortality rate is commonly the result of relentless tumour recurrence secondary to the tumour’s intrinsic resistance towards its standard chemotherapeutic agent temozolomide (TMZ).
Prolyl 4-hydroxylase, beta subunit (P4HB) is an endoplasmic reticulum stress response (ERSR) chaperone protein that was previously found to be overexpressed in the chemoresistant glioma cell lines D54-MG and U87-MG. Differential expressions of numerous microRNAs (miRNAs) were also found between chemosensitive and chemoresistant glioma cell lines. As such, we surmised that the dysregulation of a P4HB-regulating miRNA may contribute to P4HB upregulation and therefore chemoresistance in glioma. MiR-210, a commonly dysregulated miRNA in various cancers, is one of the most highly downregulated miRNAs in chemoresistant glioma cells (compared to chemosensitive glioma cells), and, based on bioinformatics findings, may also regulate P4HB expression. MiR-210 was therefore selected for further investigations regarding its potential roles in glioma chemoresistance.
The regulatory relationship between P4HB and miR-210 was subjected for verifications. With the use of quantitative real-time polymerase chain reaction (qPCR) and western blotting, the intrinsic expressions of P4HB and miR-210 were studied. The upregulation of P4HB in D54 and U87 chemoresistant glioma (compared to the parental) cell lines were found to correlate reciprocally with the downregulation of miR-210 in the same chemoresistant glioma cells.
To delineate the potential regulatory role of miR-210, a gain of function approach was adopted. Transfection of a miR-210 mimic was performed into the D54 and U87 parental chemosensitive (D54-S and U87-S) and chemoresistant (D54-R and U87-R) cells, along with a negative control. The transfection efficiency of miR-210 as well as the subsequent P4HB expressions was verified. It was found that P4HB expression was downregulated as a result of miR-210 upregulation both at the mRNA and protein levels in glioma cells. Furthermore, the effects of miR-210 overexpression on chemoresistance in the glioma cells were tested by performing cell proliferation assay. Decrease in the half maximal inhibitory concentration (IC50) of TMZ were found in all cell lines overexpressing miR-210, suggesting that miR-210 upregulation may lead to P4HB inhibition, which would at least partially mediate an alleviation of glioma cells’ resistance towards its chemotherapeutic agent TMZ.
In summary, miR-210 is downregulated in chemoresistant glioma cells in vitro. It plays a potential role in regulating P4HB expression, hence chemoresistance in GBM cells. Future investigations may focus on its mechanism of action and potentiality for therapeutic intervention.published_or_final_version
Surgery
Master
Master of Medical Sciences
37
Perry, James David. "Chemo and Radioresistance in Brain-Related Tumors." The Ohio State University, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=osu1397567849.
Full text
38
Gorgolewski, Krzysztof Jacek. "Using functional magnetic resonance imaging to plan surgical resections of brain tumours." Thesis, University of Edinburgh, 2013. http://hdl.handle.net/1842/7861.
Full textAbstract:
Brain tumours, even though rare, are one of the deadliest types of cancer. The five year survival rate for the most malignant type of brain tumours is below 5%. Modern medicine provides many options for treating brain cancer such as radiotherapy and chemotherapy. However, one of the most effective ways of fighting the disease is surgical resection. During such a procedure the tumour is partially or completely removed. Unfortunately, even after a complete resection some tumourous tissue is left behind and can grow back or metastasise to a different location in the brain. It has been shown, however, that more aggressive resections lead to longer life expectancy. This does not come without risks. Depending on tumour location, extensive resections can lead to transient or permanent post-operative neurological deficits. Therefore, when planning a procedure, the neurosurgeon needs to find balance between extending patients life and maintaining its quality. Recent developments in Magnetic Resonance Imaging (MRI) fueled by the field of human cognitive neuroscience have led to improved methods of non-invasive imaging of the brain function. Such methods allow the creation of functional brain maps of populations or individual subjects. Adapting this technique to the clinical environment enables the assessment of the risks and to plan surgical procedures. The following work aims at improving the use of functional MRI with a specific clinical goal in mind. The thesis begins with description of etiology, epidemiology and treatment options for brain tumours. This is followed by a description of MRI and related data processing methods, which leads to introduction of a new technique for thresholding statistical maps which improves upon existing solutions by adapting to the nature of the problem at hand. In contrast to methods used in cognitive neuroscience our approach is optimized to work on single subjects and maintain a balance between false positive and false negative errors. This balance is crucial for accurate assessment of the risk of a surgical procedure. Using this method a test-retest reliability study was performed to assess five different behavioural paradigms and scanning parameters. This experiment was performed on healthy controls and was aimed at selecting which paradigms produce reliable results and therefore can be used for presurgical planning. This allowed the creation of a battery of task that was applied to glioma patients. Functional maps created before the surgeries were compared with electrocortical stimulation performed during the surgeries. The final contribution of this work focuses on technical aspects of performing neuroimaging data analysis. A novel data processing framework which provides means for rapid prototyping and easy translation and adaptation of already existing methods taken from cognitive neuroscience field is introduced. The framework enables fully automatic processing of patient data and therefore greatly reduced costs while maintaining quality control. A discussion of future directions and challenges in using functional MRI for presurgical planning concludes the thesis.
39
Schackert, Gabriele. "Surgery of Brain Metastases – Pro and Contra." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-135071.
Full textAbstract:
Conclusion: Surgery should be considered whenever possible. This means that the patient has to be in good clinical condition (Karnofsky performance score > 70), the extracerebral metastases should be stable, the number of cerebral lesions should not exceed more than 3 seedings, and the age of the patient should be below 70 years. Since brain metastases are usually well circumscribed, complete extirpation seems to be possible. Postoperative MRI should be demanded in order to confirm complete extirpation. Additional radiotherapy is indicated in case of subtotal resection of a single lesion and in multiple lesions. In single brain metastasis a prospective randomized trial is necessary to prove whether conventional radiotherapy is essential after surgery in the primary treatment of the tumors or can be delayed until cerebral lesions recur. Radiosurgery is an alternative to surgery in the treatment of metastasisDieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich
40
Tomson, Derek. "Evaluating the association between adult primary brain tumours and a family history of cancer." Thesis, University of Ottawa (Canada), 2006. http://hdl.handle.net/10393/27301.
Full textAbstract:
There are very few established causes of primary brain tumours in adults. Associated with short survival times, increasing effort is being put forth in an attempt to better understand the risk factors of these neoplasms, including investigating the possible relationship with a family history of cancer and germline genetic polymorphisms. This thesis was conducted to evaluate both of these potential associations.
Using an international population-based case-control study, the self-reported family histories of cancer were compared between 1089 glioma cases and 1922 matched controls and between 307 meningioma cases and 1095 controls. Significantly lowered odds of glioma were associated with the reporting of any type of cancer in a first degree relative (OR = 0.8, 95% CI = 0.7-0.99) and with any type of cancer excluding brain tumours (OR = 0.8, 95% CI = 0.7-0.9). No significant associations were found amongst the meningioma cases and controls, though elevated point estimates were found for those reporting parental lung and genitourinary cancers, while the presence of breast, lip, oral, pharyngeal and unspecified cancers all produced great reductions in meningioma odds, suggesting that further study is required.
In order to evaluate the association between adult brain tumours and genetic polymorphisms, a systematic review of the literature was completed. A total of 41 case-control studies were included, covering 46 separate genes and more than 100 different single nucleotide polymorphisms. When possible, quantitative data synthesis was performed to establish a more refined point estimate and confidence intervals. Heterogeneity across the studies and variability in the subject matter often prevented any possible data synthesis so establishing associations that were statistically significant was difficult. All told, there were 41 significant associations found amongst the included studies and each varied by the particular polymorphism or histology studied. None of the estimates produced in the quantitative data syntheses suggested a statistically significant association.
The results of this thesis suggest that a family history of cancer is not a risk factor for primary brain tumours in adults and that further work is necessary to better establish the possible association between various genetic polymorphisms and adult brain tumours.
41
Au, Wing-han. "Brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TRKB) signaling in ovarian cancer." Click to view the E-thesis via HKUTO, 2007. http://sunzi.lib.hku.hk/HKUTO/record/B39557947.
Full text
42
Lal, Priya Kumari. "Maternal prenatal consumption of bioflavonoids and phenolic acids and risk of childhood brain cancer." Columbus, Ohio : Ohio State University, 2004. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1080569687.
Full textAbstract:
Thesis (Ph. D.)--Ohio State University, 2004.Title from first page of PDF file. Document formatted into pages; contains xvii, 274 p.; also includes graphics (some col.). Includes abstract and vita. Advisor: J. Schwartzbaum, School of Public Health. Includes bibliographical references (p. 171-203).
43
Chow, Benjamin Yew Loong. "Modulated Electro-Hyperthermia in the Treatment of Brain Cancers: A Study of Safety and Effects." Thesis, University of Sydney, 2020. https://hdl.handle.net/2123/23906.
Full textAbstract:
Brain cancer is one of the deadliest forms of cancer with 5 year survival rates recording around 22% with no improvements over several decades. Current treatment methods rarely deviate from surgery, radiotherapy and chemotherapy. Modulated Electro-Hyperthermia (sometimes referred to as oncothermia) is a non-invasive cancer treatment method which uses non-ionising 13.56 MHz radiofrequency radiation to induce therapeutic hyperthermia in tumours. Repeated treatment using this method has been shown to cause tumour cell apoptosis. The technology is currently being used in Europe, parts of Asia and America. Resistance to the uptake of this technology is based on lack of understanding of how to optimally use the device and concerns over safety of the patient regarding overheating. Current protocols utilise a step-wise increment of power dosage using patient discomfort as an indicator. However, discomfort is not a reliable feedback mechanism, particularly when treating brain cancer. This thesis investigates four different points. Firstly, what is the relationship between energy dose and resulting temperature? Does the clinical device accurately measure internal temperatures? Does the treatment have any side effects on healthy brain tissue? Finally, what clinical monitoring protocol could be used to ensure optimal treatment of patients? These research questions were investigated using a variety of experimental techniques. Phantom models were designed and used to study the relationship of energy dose to temperature profile and accuracy of temperature measurement. Animal models were used to study potential side effects on the brain. Lastly, image processing techniques were used to develop a clinical monitoring system. It was determined that hydration, electrolyte balance, tissue composition and location of the treatment area had important roles in determining optimal energy dosage. While no gross tissue damage occurred from optimal treatment usage, there is cellular response to the treatment. Tumour volumes and locations can be analysed from diagnostic MRI scans to aid optimisation of treatment protocol.
44
Ailion, Alyssa S. "Longitudinal Analysis of Risk Factors Affecting Reading Trajectories in Children Diagnosed with Pediatric Brain Tumors." Digital Archive @ GSU, 2012. http://digitalarchive.gsu.edu/honors_theses/7.
Full textAbstract:
Prior research suggests aggressive cancer treatments contribute to cognitive impairments in children diagnosed with pediatric brain tumors. The literature also suggests that younger age at diagnosis (AAD) and treatment may result in disrupted cognitive trajectories due to limited brain plasticity. In line with this research, we hypothesized an interaction between radiation therapy (RT) and young AAD of brain tumors, where young AAD and RT results in lower standard scores on the WRAT-R Reading Comprehension Subtest. Analyses included archival data; the sample consists of 134 children diagnosed with pediatric brain tumors with multiple assessments resulting in 487 cases for analysis. Participants were diagnosed with mixed tumor types and locations. A two level multilevel model was used to analyze reading trajectories while taking into account AAD, time since diagnosis, socioeconomic status (SES), and RT. Results detected a positive interaction between AAD and RT (γ =2.08, p=.02). For participants with RT, younger AAD was associated with lower reading scores, whereas AAD had no effect for participants without RT. Results also detected a negative interaction between radiation and time (γ =-2.29, p=.00) indicating that children treated with RT have reading scores that decrease over time. These data suggested that children diagnosed with pediatric brain tumors treated with RT are at higher risk of reading impairment as reflected in their reading scores.
45
Schackert, Gabriele. "Surgery of Brain Metastases – Pro and Contra." Karger, 2002. https://tud.qucosa.de/id/qucosa%3A27616.
Full textAbstract:
Conclusion: Surgery should be considered whenever possible. This means that the patient has to be in good clinical condition (Karnofsky performance score > 70), the extracerebral metastases should be stable, the number of cerebral lesions should not exceed more than 3 seedings, and the age of the patient should be below 70 years. Since brain metastases are usually well circumscribed, complete extirpation seems to be possible. Postoperative MRI should be demanded in order to confirm complete extirpation. Additional radiotherapy is indicated in case of subtotal resection of a single lesion and in multiple lesions. In single brain metastasis a prospective randomized trial is necessary to prove whether conventional radiotherapy is essential after surgery in the primary treatment of the tumors or can be delayed until cerebral lesions recur. Radiosurgery is an alternative to surgery in the treatment of metastasis.Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.
46
Lungu, Gina Florentina. "Role of hypoxia and hypoxia induced factors in the development of breast cancer brain metastasis." [College Station, Tex. : Texas A&M University, 2008. http://hdl.handle.net/1969.1/ETD-TAMU-3082.
Full text
47
Lakkadwala, Sushant. "Dual Functionalized Liposomes for Co-delivery of Anti-cancer Chemotherapeutics for Treatment of Brain Tumor." Diss., North Dakota State University, 2019. https://hdl.handle.net/10365/29394.
Full textAbstract:
Glioblastoma is a hostile brain tumor associated with high infiltration leading to poor prognosis. Currently available treatment options are insufficient to increase median survival time. The combination therapy has emerged as an efficient way to deliver chemotherapeutics for treatment of glioblastoma. It provides collaborative approach of targeting cancer cells by acting via multiple mechanisms, thereby reducing drug resistance. However, the presence of selective and impermeable blood brain barrier (BBB) restricts the delivery of chemotherapeutic drugs into the brain. To overcome this limitation, we designed a dual functionalized liposomes by modifying their surface with transferrin (Tf) and a cell penetrating peptide (CPP) for receptor and adsorptive mediated transcytosis, respectively. In this study, we used various CPPs based on their physicochemical properties (TAT, penetratin, QLPVM and PFVYLI) and investigated the influence of insertion of CPP to Tf-liposomes on cytotoxic potential, cellular uptake, hemocompatibility and transport across the BBB both in vitro and in vivo. In addition, anti-tumor efficacy of dual functionalized liposomes was evaluated in vitro as well as in vivo. The liposomes were encapsulated with chemotherapeutics agents, doxorubicin and erlotinib for delivery to brain. Co-delivery of doxorubicin and erlotinib loaded Tf-CPP liposomes revealed significantly (p < 0.05) higher translocation more than 12 % across the co-culture endothelial barrier resulting in regression of tumor in the in vitro brain tumor model. The biodistribution of Tf-CPP liposomes demonstrated more than 10 and 2.7 fold increase in doxorubicin and erlotinib accumulation in mice brain, respectively compared to free drugs. Histological evaluation of tissue sections showed no signs of toxicity. In addition, Tf-Pen liposomes showed excellent antitumor efficacy by regressing ~90% of tumor in mice brain with significant increase in the median survival time (36 days). In conclusion, we have developed a high efficiency liposomal drug delivery carrier that can cross the BBB and co-deliver doxorubicin and erlotinib to desired target tumor site in vivo in mice, thereby 1) increased concentration of chemotherapeutics in brain, 2) regression in glioblastoma tumor size, 3) reducing the possibility of drug resistance in cancer cells, without eliciting undesired toxicity.National Institutes of Health (NIH Grant RO1 AG051574)
ND EPSCoR
48
Ascha, Mustafa Steven. "Incidence and Treatment of Brain Metastases Arising from Lung, Breast, or Skin Cancers: Real-World Evidence from Primary Cancer Registries and Medicare Claims." Case Western Reserve University School of Graduate Studies / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=case1554481284740082.
Full text
49
Vagena, Eirini. "Your brain on fat : the role of diet in depression like behaviours." Thesis, University of Glasgow, 2014. http://theses.gla.ac.uk/5800/.
Full textAbstract:
Epidemiological and clinical studies indicate that overweight and obesity are associated with increased risk for depression, but the mechanisms linking dietary components with the development of depression phenotype are poorly understood. To investigate this relationship, we utilized lipidomic and transcriptomic methods to evaluate the effects of diet on the brain.
50
Piel, Clément. "Tumeurs du système nerveux central et expositions agricoles aux pesticides." Thesis, Bordeaux, 2018. http://www.theses.fr/2018BORD0466/document.
Full textAbstract:
Dans la littérature internationale, les expositions agricoles aux pesticides constituent une hypothèse privilégiée pour expliquer l’excès de tumeurs cérébrales observé chez les agriculteurs. L’objectif de cette thèse, élaborée à partir des données de la cohorte Agrican, était d’investiguer le rôle des expositions agricoles aux pesticides dans l’incidence des principaux types histologiques de tumeurs du système nerveux central. Avec plus de 180 000 participants suivis depuis 2005, la cohorte Agrican est une des plus grandes études sur la santé en milieu agricole. En tenant compte des principaux facteurs de confusion, des comparaisons internes ont fait apparaitre des augmentations de risque chez les agriculteurs, plus marquées chez les utilisateurs de pesticides, et avec de fortes variations selon les types de cultures et d’élevages. Suite à ces premières analyses, un travail de priorisation a permis d’identifier les pesticides carbamates comme prioritaires à étudier en lien avec les tumeurs cérébrales. La poursuite du développement de la matrice Pestimat a ensuite permis de reconstituer l’historique des utilisations de carbamates depuis 1950 dans les principaux contextes agricoles français. À l’issue de ces étapes intermédiaires, des analyses de survie menées chez les participants d’Agrican ont fait apparaître des augmentations de risque de gliomes et de méningiomes en lien avec les expositions professionnelles à des matières actives (dithio/thio)-carbamates, en particulier avec celles dont l’utilisation a été recommandée en viticulture, en arboriculture et sur cultures de pomme de terre et de betterave. Ces résultats renforcent les preuves de cancérogénicité pour les pesticides déjà suspectés pour d’autres cancers et attirent l’attention sur d’autres matières actives, moins documentées dans la littérature mais relativement homogènes au niveau des structures chimiques. Aussi, sur la base de ces résultats et dans un objectif de santé publique, il paraît essentiel de poursuivre les efforts engagés pour réduire les expositions aux pesticides des agriculteursIn the international literature, agricultural exposures to pesticides have been put forward as a key hypothesis to explain the excess of brain tumours observed in farmers. The aim of this thesis, based on data from the Agrican cohort, was to investigate the role of agricultural exposures to pesticides in the incidence of the main histological types of central nervous system tumours. With more than 180,000 participants followed since 2005, the Agrican cohort is one of the largest studies on health in agriculture. Internal comparisons adjusted for the main important confounders showed increases in risk among farmers, more pronounced risk among pesticide users, and with strong variations according to the types of crop and livestock farming. Following these initial analyses, work identified carbamate pesticides as a priority to study in relation to brain tumours. Next, further development of the Pestimat served to reconstitute the history of carbamate uses since 1950 in the main French agricultural contexts. After these intermediate steps, survival analyses conducted among Agrican participants showed increased risks of glioma and meningioma in farmers exposed to (dithio/thio)-carbamates, particularly with those recommended for use on vineyards, fruits, potatoes and beets. These findings reinforce the evidence of carcinogenicity among pesticides already suspected for other cancers, and draw attention to other active ingredients, less documented in the literature but relatively homogeneous in terms of chemical structures. Therefore, on the basis of these conclusions and with a public health objective in mind, it seems essential to pursue efforts to reduce farmers' exposure to pesticides