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Enyakoit, G. O. "Cytogenetic analysis of DNA copy number aberrations in high malignancy grade astrocytomas." Thesis, University College London (University of London), 2008. http://discovery.ucl.ac.uk/1444158/.
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Astrocytomas are the most common variety of primary tumours of the central nervous system (CNS). The incidence increases with age, peaking in patients aged 65--75 years. They are generally unresponsive to treatment, and most patients die within one year of diagnosis. Recent genetic studies of astrocytoma susceptibility syndromes, familial- and sporadic astrocytomas have led to the discovery of many genes and molecular mechanisms underlying astrocytoma oncogenesis. A few of the genes involved in inherited astrocytoma associated-syndromes (e.g., Cowden and Li-Fraumeni syndromes) are also strongly implicated in sporadic astrocytomas. However for several other well characterised genes i.e. those mutated in Tuberous sclerosis (TSC) and Neurofibromatosis (NF) any evidence for involvement in sporadic astrocytomas is much less clear. The objective of this study was to undertake a genome-wide survey of high malignancy grade astrocytomas with a view to ascertaining the distribution and prevalence of copy number aberrations, search for associations with prognosis and outcomes to treatment, and to discover possible novel pathways of oncogenesis. Thirty-two high malignancy grade astrocytomas were investigated. Twenty were available as frozen biopsies and 12 as short-term cell cultures. Genomic profiling of all 32, comprising 6 tumours of WHO Grade III and 26 of Grade IV, was achieved by the method of Comparative Genomic Hybridisation onto metaphase chromosomes. 7 of the tumours were investigated by array CGH, with one further investigated by MFISH. Two tumours did not reveal aberrations. For the other 30 tumours, data pooled from a minimum of 10 profiles of each tumour were analysed. Recurrent DNA copy number gains and losses were detected across the genome. In a number of tumours aberrations spanned loci of established candidate genes previously associated with sporadic astrocytomas, on chromosomes 7, 9p, lOq, 12q, 13q and 17p. In addition over 70% of 'sporadic' tumours appeared to have DNA-copy number aberrations implicating genes with established roles in astrocytoma-susceptibility syndromes. The chromosomal region 9q34 (site of TSC1) appeared to be under-represented in 25% of the tumours, while 16pl3 (site of TSC2) was diminished in -38%. Similarly, loci for NF1 and NF2 were involved in aberrations in -10% and 38% of the cases respectively, as were those of PMS2 (22%), APC (19%) and a number of miss- I Cytogenetic Analysis of DNA Copy Number Aberrations in High Malignancy Grade Astrocytomas match repair (MMR) genes. Eight tumours had probable loss at lp36. Several novel locations were also suggested An attempt to correlate DNA copy number alterations with survival showed that among patients with grade IV tumours, there were on average far fewer chromosome aberrations per tumour in four of the five patients surviving longer than one year after diagnosis than in those who died before this. There was some suggestion of a worse prognosis in Grade IV tumours with a specific deletion of lp36, which would agree with a previous report. The only Grade IV tumour that was studied by all three approaches showed good agreement between array and metaphase CGH. In addition, array CGH revealed small regions of loss in the region of PTEN (CHR lOq) and TP53 (CHR 17p) below the resolution of the metaphase CGH. The M-FISH revealed very large numbers of chromosomes and several translocations, and comparison of the microarray data and the MFISH data suggests possible candidate regions for breakpoints. The data are discussed in the light of previous work and with a view to the possibility that there may be some diversity in the cellular origin of astrocytomas and that haploinsufficiency may play some role in oncogenesis.
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Enyakoit, George Ojula. "A genome-wide investigatin of DNA copy number aberrations in high malignancy grade astrocytomas." Thesis, University College London (University of London), 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.500063.
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Brown, I. "High linear energy transfer endoradiotherapeutic drugs for malignant disease." Thesis, University of Cambridge, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.596984.
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Jackson, L. A. "Cytogenetic and molecular genetic analysis of normal, pre-malignant and malignant breast tissue from patients in high-risk families." Thesis, University of Cambridge, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.604988.
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The data presented in this thesis demonstrates that 60.0% of the morphologically normal samples from women at high risk for breast cancer showed genomic copy number aberrations by CGH. There was an average of 1.45 aberrations per sample analysed. These aberrations seemed to be spread throughout the genome, however, there were some regions of interest. These were gains on 1p, 9p, 16p 16q and 19. The presence of these aberrations suggests that morphologically normal epithelial cells analysed from these cases have a degree of genomic instability. The CGH results for HUT presented a complicated profile of copy number loss and gain spread throughout the genome. Of the 23 lesions successfully analysed by CGH, 96.7% had genomic aberrations, an average of 4.35 aberrations per sample analysed. The most common sites of aberration were loss at 1p, 9q, 17p, 17q, 19 and 22q and again at 1q, 2q, 6q, 9p, 13q, 18p and X. The immunohistochemical staining of the HUT provided an insight into whether the lesion was derived from a single clone or was a proliferation of a number of cells. However the overall staining patterns were highly variable between and within cases and no common observations were identified. Although the numbers in this study are small and there is a lack of <i>BRCA1 </i>and <i>BRACA2</i> mutation status information in all samples, there does seem to be a trend towards the <i>BRCA</i> mutation positive samples being more likely to have genomic aberrations and for these samples to have an increased number of aberrations over samples with unknown mutation status. The wide variety copy number losses and gains in these samples suggest that premalignant lesions can, and do, acquire an array of aberrations and still present as a similar morphological lesions.
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Arlotta, Paola. "The high mobility group protein I-C : transcriptional regulation and involvement in the formation of lipomas in transgenic mice." Thesis, University of Portsmouth, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.311184.
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Garcia, Paulo A. "Irreversible Electroporation for the Treatment of Aggressive High-Grade Glioma." Diss., Virginia Tech, 2010. http://hdl.handle.net/10919/77269.
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Malignant gliomas (MG), most notably glioblastoma multiforme (GBM), are among the most aggressive of all malignancies. High-grade variants of this type of brain cancer are generally considered incurable with singular or multimodal therapies. Many patients with GBM die within one year of diagnosis, and the 5-year survival rate in people is approximately 10%. Despite extensive research in diagnostic and therapeutic technologies, very few developments have emerged that significantly improve survival over the last seven decades.
Irreversible electroporation (IRE) is a new non-thermal focal tissue ablation technique that uses low-energy electric pulses to destabilize cell membranes, thus achieving tissue death. The procedure is minimally invasive and is performed through small electrodes inserted into the tissue with treatment duration of about one minute. The pulses create an electric field that induces an increase in the resting transmembrane potential (TMP) of the cells in the tissue. The induced increase in the TMP is dependent on the electric pulse parameters. Depending on the magnitude of the induced TMP the electric pulses can have no effect, transiently increase membrane permeability or cause spontaneous death.
In this dissertation we hypothesize that irreversible electroporation is capable of ablating normal (gray and white matter) and pathological (MG and/or GBM) brain tissue in a highly focused non-thermal manner that is modulated through pulse parameters and electrode configuration. Through a comprehensive experimental and numerical investigation, we tested and attained results strongly supporting our hypothesis. Specifically, we developed numerical models that were capable of simulating an entire IRE treatment protocol and would take into account pulse parameters (e.g. duration, frequency, repetition rate and strength) in addition to the dynamic changes in tissue electrical conductivity due to electroporation and joule heating, as well as biologically relevant processes such as blood perfusion and metabolic heat. We also provided a method to isolate the IRE effects from undesired thermal damage in models that were validated with real-time temperature measurements during the delivery of the pulses. Finally we outlined a procedure to use 3D volumetric reconstructions of IRE lesions using patient specific MRI scans in conjunction with the models described for establishing field thresholds or performing treatment planning prior to the surgical procedure; thus supplying the readers with the tools and understanding necessary to design appropriate treatment protocols for their specific application.
Experimentally we presented the first systematic in vivo study of IRE in normal canine brain and the multimodal treatment of a canine MG patient. We confirmed that the procedure can be applied safely in the brain and was well tolerated clinically. The lesions created with IRE were sub-millimeter in resolution and we achieved 75% tumor volume reduction within 3 days post-IRE in the patient. In addition to the sharp delineation between necrotic and normal brain, the treatments spared the major blood vessels, making it appropriate for treatment of tumors adjacent to, or enveloping critical vascular structures. We believe that irreversible electroporation will play a key role in the treatment of intracranial disorders including malignant brain cancer in which the intent is to focally kill undesired tissue while minimizing damage to surrounding healthy tissue.<br>Ph. D.
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Chikada, Ai. "A descriptive analysis of end-of-life discussions for high-grade glioma patients." Doctoral thesis, Kyoto University, 2021. http://hdl.handle.net/2433/264666.
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京都大学<br>新制・課程博士<br>博士(人間健康科学)<br>甲第23385号<br>人健博第92号<br>新制||人健||6(附属図書館)<br>京都大学大学院医学研究科人間健康科学系専攻<br>(主査)教授 田村 恵子, 教授 稲富 宏之, 教授 溝脇 尚志<br>学位規則第4条第1項該当<br>Doctor of Human Health Sciences<br>Kyoto University<br>DFAM
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Ivey, Jill Winters. "Investigating the Applications of Electroporation Therapy for Targeted Treatment of Glioblastoma Multiforme Based on Malignant Properties of Cells." Diss., Virginia Tech, 2017. http://hdl.handle.net/10919/78806.
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Glioblastoma multiforme (GBM) is the most common and lethal primary brain cancer with an average survival time of 15 months. GBM is considered incurable with even the most aggressive multimodal therapies and is characterized by near universal recurrence. Irreversible electroporation (IRE) is a cellular ablation method currently being investigated as a therapy for a variety of cancers. Application of IRE involves insertion of electrodes into tissue to deliver pulsed electric fields (PEFs), which destabilize the cell membrane past the point of recovery, thereby inducing cell death. While this treatment modality has numerous advantages, the lack of selectivity for malignant cells limits its application in the brain where damage to healthy tissue is especially deleterious. In this dissertation we hypothesize that a form of IRE therapy, high-frequency IRE (H-FIRE), may be able to act as a selective targeted therapy for GBM due to its ability to create an electric field inside a cell to interact with altered inner organelles. Through a comprehensive investigation involving experimental testing combined with numerical modeling, we have attained results in strong support of this hypothesis. Using tissue engineered hydrogels as our platform for therapy testing, we demonstrate selective ablation of GBM cells. We develop mathematical models that predict the majority of the electric field produced by H-FIRE pulses reach the inside of the cell. We demonstrate that the increased nuclear to cytoplasm ratio (NCR) of malignant GBM cells compared to healthy brain—evidenced in vivo and in in vitro tissue mimics—is correlated with greater ablation volumes and thus lower electric field thresholds for cell death when treated with H-FIRE. We enhance the selectivity achieved with H-FIRE using a molecularly targeted drug that induces an increase in NCR. We tune the treatment pulse parameters to increase selective malignant cell killing. Finally, we demonstrate the ability of H-FIRE to ablate therapy-resistant GBM cells which are a focus of many next-generation GBM therapies. We believe the evidence presented in this dissertation represents the beginning stages in the development of H-FIRE as a selective therapy to be used for treatment of human brain cancer.<br>Ph. D.
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Callanan, Mary. "Caractérisation moléculaire d'une t(1;22)(q21;q11) impliquée dans la progression tumorale dans les lymphomes malins non Hodgkiniens." Université Joseph Fourier (Grenoble ; 1971-2015), 1997. http://www.theses.fr/1997GRE10177.
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Les rearrangements du bras long du chromosome 1 sont parmi les plus frequemment observes dans les tumeurs humaines. La plupart de ces rearrangements impliquent la bande chromosomique 1q21. Ce sont soit des translocations desequilibrees soit moins frequemment des translocations equilibrees avec de nombreux chromosomes partenaires. Ces anomalies surviennent plutot au cours de l'evolution d'une tumeur et seraient donc impliquees dans la progression tumorale. Cependant elles ont aussi ete observees dans des etats preneoplasiques precedant de plusieurs mois, voire annees, l'eclosion de la tumeur maligne. Malgre leur frequence elevee et leur role potentiel dans les processus de tumorogenese, on ne connait ni les genes cibles de ces rearrangements en 1q21, ni les sites de cassure preferentiels. A ce titre, l'objectif de ce travail etait de cloner et caracteriser les points de cassure d'une translocation t(1;22) observee dans une lignee tumorale (b593) etablie a partir d'un lymphome de haut grade de malignite. Cette translocation implique sur le chromosome 1 la bande 1q21, point chaud de cassures dans les lymphomes, et sur le chromosome 22 la bande 22q11, locus des genes d'immunoglobulines lambda. Le fragment de jonction de cette translocation a ete clone, cartographie en detail et differents clones appartenant a la bande 1q21 isoles. La recherche systematique de sequences transcrites dans une region de 16,5kb entourant la jonction n'a revele la presence d'aucune unite transcriptionnelle fonctionnelle. Cependant un pseudogene original de la proteine ribosomique l31 a ete identifie a 6kb de la jonction et la lignee b593 montre un taux eleve d'arnm l31. Ce pseudogene presente les caracteres habituels des retroposons, il est flanque par des repetitions directes, ne comporte pas d'introns et porte une queue poly a. Il est cependant particulier du fait de la presence en 5' d'une sequence polypyrimidique terminale (5' terminal oligopyrimidine tract - 5' top), site d'initiation transcriptionnelle caracteristique des genes codant pour des proteines ribosomiques. Cette sequence est precedee d'une boite type tata, alors que les promoteurs de genes codant pour les proteines ribosomiques en sont depourvus. La signification de ces resultats dans le contexte d'une expression elevee de l31 est discutee. Afin de preciser la localisation du point de la cassure 1q21 observee dans la lignee b593, nous l'avons positionne par fish sur la carte physique/genetique integree du consortium du ceph, a l'aide de yacs de cette region. Cette approche a permis de localiser le point de cassure dans un grand intervalle de 8cm borne par les yacs 910c8 en position proximale et 907a11 en position distale, une region jusqu'alors non impliquee dans des cancers. Des yacs specifiques de la jonction ont ensuite ete isoles par criblage de la banque de yacs du ceph avec des amorces specifiques du point de cassure, permettant l'identification du yac 851a10 chevauchant le point de cassure 1q21 de la lignee b593. Le point de cassure d'une autre t(1;22) observee chez un deuxieme malade a egalement ete localise dans ce yac. Ce resultat suggere l'existence d'au moins un site oncogenique dans la region de 1q21 homologue au yac 851a10.
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Nkosana-Nyawata, Idah D. "Understanding delay : a grounded theory examination of the pre-diagnostic journey of individuals with malignant melanoma. An analysis of the experiences of individuals subsequently diagnosed with high risk malignant melanoma from problem identification through to initial specialist treatment." Thesis, University of Bradford, 2008. http://hdl.handle.net/10454/4314.
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Nkosana-Nyawata, Idah Dzanisa. "Understanding delay : a grounded theory examination of the pre-diagnostic journey of individuals with malignant melanoma : an analysis of the experiences of individuals subsequently diagnosed with high risk malignant melanoma from problem identification through to initial specialist treatment." Thesis, University of Bradford, 2008. http://hdl.handle.net/10454/4314.
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Hussenet, Thomas. "Toward the identification of oncogenes by high resolution mapping of gene amplifications of the 3q25-qter region in malignant fibrous histiocytoma and squamous cell carcinoma." Strasbourg 1, 2005. https://publication-theses.unistra.fr/public/theses_doctorat/2005/HUSSENET_Thomas_2005.pdf.
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L’approche de clonage positionnel a été appliquée à la cartographie haute résolution des aberrations du chromosome 3 dans différents types tumoraux afin d’identifier de nouveaux candidats oncogènes du bras long du chromosome 3 (3q), amplifiés et sur-exprimés en conséquence. Une première partie a été dédiée aux Fibro-Histiocytomes Malins (MFH). Des amplicons chevauchants du locus 3q28 ont été caractérisés dans une lignée cellulaire et deux tumeurs de MFH. A ce locus, nous avons identifié un oncogène candidat, hsa-miR-28, codant pour un microARN ainsi que trois de ses cibles, impliquées dans la régulation du cycle cellulaire. Une seconde partie concerne les carcinomes épidermoïdes (SCC). Nous avons analysé les aberrations du chromosome 3 dans 25 SCC du poumon par hybridation génomique comparative sur puces à ADN (CGH array) et défini une région consensus de 2 Mb au locus 3q26. 3 amplifiée à haut niveau dans 20% des cas. L’analyse des conséquences transcriptionnelles pour 9 gènes a montré que la plupart sont sur-exprimés de manière récurrente mais deux, SOX2 et SOX2OT, représentent vraisemblablement les cibles des amplifications du locus. Nous avons également isolé le gène cyclin L1 au locus 3q25. 3 comme oncogène candidat dans les SCC des Voies Aéro-Digestives Supérieures (VADS). Le nombre de copies du gène est très fréquemment augmenté dans ces tumeurs et le gène surexprimé. Finalement, nous avons caractérisé par CGH array différentes amplifications du 3q dans une série de 25 SCC des VADS, définissant une région commune avec les SCC du poumon suggérant ainsi que des gènes similaires du locus 3q26. 3 sont impliqués dans les SCC indépendamment de leur localisation. En conclusion, nous avons isolé sur le bras long du chromosome 3 différents candidats oncogènes dans plusieurs types tumoraux, ce qui illustre la puissance de l’approche de clonage positionnel appliquée aux génomes tumoraux. Des travaux sont encore nécessaires pour vérifier leur statut oncogénique<br>This thesis work specifically applied the positional cloning strategy to the high resolution mapping of chromosome 3 aberrations in different tumour types to identify new candidate oncogenes located at 3q, amplified and consequently over-expressed. A first part was dedicated to Malignant Fibrous Histiocytomas (MFH). We first characterized overlapping amplicons at 3q28 in a MFH cell line and two other MFH primary tumours. From this region, we identified a microRNA encoding gene, hsa-miR-28 as an oncogene candidate and further identified three targets of miR-28 which all play roles in cell cycle regulation. A second part was dedicated to Squamous Cell Carcinoma (SCC). We analyzed chromosome 3 aberrations in a series of 25 lung SCC using array CGH and delineated a common region of high-level amplifications at 3q26. 3 for 20% of the tumours. Further high-resolution mapping pinpoint a 2 Mb consensus region. Analyses of the transcriptional consequences of these high-level amplifications were carried out for 9 genes. Most of them are recurrently over-expressed but two, SOX2 and SOX2OT, likely represent the 3q26. 3 amplification driver genes. Our strategy also enabled us to isolate cyclin L1 (CCNL1) gene at 3q25. 3 as a candidate oncogene in head and neck SCC (HNSCC). Investigations of CCNL1 gene alterations in a large series of HNSCC revealed consistent copy number gains and over-expression. Using array CGH we finally delineated several high-level amplifications at 3q in a series of 25 analyzed HNSCC, defining a common region overlapping with the consensus region defined for lung SCC thus suggesting that similar genes at 3q26. 3 may be involved in SCC pathogenesis independently of the localization. In conclusion we were able to isolate several candidate oncogenes located at 3q in different tumour types, illustrating the power of the positional cloning strategy applied to tumour genomes. Further investigations are needed to assess their oncogenic status
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Leventoux, Nicolas. "Etude des foyers d’hétérogénéité tumorale dans les gliomes diffus de bas grade de l’adulte mutés IDH1." Thesis, Montpellier, 2018. http://www.theses.fr/2018MONTT037.
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Les gliomes sont les principales tumeurs primitives du cerveau affectant environ 4000 nouveaux patients par an en France. La moitié des gliomes est détectée au stade avancé de glioblastome (grade IV) tandis que 15% des tumeurs sont diagnostiquées au stade II de gliomes diffus dit de bas grade. Ces tumeurs affectent des patients jeunes et présentent des mutations caractéristiques, notamment une mutation pour l’enzyme IDH1 communément retrouvée dans les glioblastomes secondaires. Ces tumeurs de bas grade sont traitées par une chirurgie, idéalement en condition éveillée mais du fait de leur nature diffuse, la partie résiduelle progressera inexorablement vers un stade III ou IV avec une survie globale entre 5 ans et 15 ans après diagnostique. La progression tumorale est hautement variable et non prédictible d’un patient à l’autre. Des foyers de progression tumorale chez 20% des patients atteints de gliome diffus de bas grade ont été identifiés. Ces foyers montrent une densité cellulaire plus élevée ainsi qu’un Ki67 augmenté. Mon travail de thèse aura consisté à étudier les modifications cellulaires et moléculaires associées à ces foyers de progression tumorale. À partir du profil ARN des foyers et des territoires adjacents, j’ai pu mettre en évidence par des techniques haut-débit la baisse d’expression significative de gènes dans les foyers notamment de AGXT2L1/ETNPPL, carboxypeptidase E, EDNRB, SFRP2. J’ai émis l’hypothèse que SFRP2 et ETNPLL pourraient s’opposer à la prolifération cellulaire et que leur diminution dans les foyers ouvrirait la voie à la transformation tumorale. Une corrélation inverse entre la quantité d’ETNPPL enzyme et la survie de patients atteints d’hépatocarcinomes a été publiée. En limitant la quantité de précurseurs de phospholipides dans la cellule, ETNPPL pourrait agir comme un frein en s’opposant à la prolifération et de fait, sa diminution dans les foyers de transformation des gliomes pourrait lever cette inhibition. Mes travaux auront été innovants tant dans leur approche comparative des différents compartiments tumoraux pour chaque patient étudié et auront révélés ETNPPL comme corrélé à la gliomagenèse et potentielle cible thérapeutique<br>Gliomas are the main primary brain tumours affecting around 4000 new patients in France each year. Half of gliomas are detected in the advanced stage of glioblastoma (grade IV) while 15% of tumours are diagnosed in stage II (diffuse low-grade gliomas-DLGG). These tumors affect young patients and bear characteristic mutations, including a mutation for the enzyme IDH1 commonly found in secondary glioblastomas. These low-grade tumours are treated by surgery, ideally in awake condition but due to their diffuse nature, the residual part will progress inexorably to stage III or IV with overall survival between 5 and 15 years after diagnosis. Tumor progression is highly variable and unpredictable from one patient to another. Foci of tumor progression have been identified in 20% of patients with DLGG. These foci show a higher cell density and an increased Ki67. My thesis work consisted in studying the cellular and molecular changes associated with tumor progression. From the RNA profile of the foci and adjacent territories, I was able to highlight through high-throughput techniques significant decrease in gene expression in the foci, particularly of AGXT2L1/ETNPPL, carboxypeptidase E, EDNRB, SFRP2. I hypothesized that SFRP2 and ETNPLL could oppose cell proliferation and that their decrease would pave the way for tumor transformation. An inverse correlation between the amount of ETNPPL and the survival of patients with hepatocarcinoma has been published. By limiting the amount of phospholipid precursors in the cell, ETNPPL could act as a brake against proliferation and indeed, its decrease in glioma transformation foci could remove this inhibition. My PhD work will have been innovative in the comparative approach of the different tumors’ compartments for each patient studied and will have revealed ETNPPL as correlated to gliomagenesis and as potential therapeutic target
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Ciappuccini, Renaud. "Apport de l'imagerie fonctionnelle par TEMP/TDM et TEP/TDM dans la prise en charge des cancers différenciés de la thyroïde Incremental Value of a Dedicated Head and Neck Acquisition during 18F-FDG PET/CT in Patients with Differentiated Thyroid Cancer Full text links full-text provider logo Actions Favorites Share Page navigation Title & authors Abstract Conflict of interest statement Figures Similar articles Cited by References Related information LinkOut - more resources EJNMMI Res . 2018 Dec 3;8(1):104. doi: 10.1186/s13550-018-0461-x. Optimization of a dedicated protocol using a small-voxel PSF reconstruction for head-and-neck 18 FDG PET/CT imaging in differentiated thyroid cancer 78 Lymph node involvement in head-and-neck and thyroid cancers with digital PET/CT: the impact of ultra-high definition voxels and point-spread function Tumor burden of persistent disease in patients with differentiated thyroid cancer: correlation with postoperative risk-stratification and impact on outcome 133 18F-Fluorocholine PET/CT is a highly sensitive but poorly specific tool for identifying malignancy in thyroid nodules with indeterminate cytology: The Chocolate study PSMA expression in neovasculature of persistent/recurrent differentiated thyroid cancerin the neck: relationship with radioiodine uptake, 18Fluorodeoxyglucose avidity and outcome." Thesis, Normandie, 2020. http://www.theses.fr/2020NORMC424.
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L’imagerie scintigraphique des cancers thyroïdiens différenciés (CTD) présente la particularité d’utiliser deux radiopharmaceutiques, l’iode 131 (131I) et le 18-Fluorodésoxyglucose (18FDG). La fixation de ces traceurs dépend habituellement du degré de différenciation et de l’agressivité de la tumeur. L’objectif de ce travail était d’étudier l’apport de différents aspects techniques et d’instrumentation, à savoir l’imagerie hybride par TEMP/TDM et TEP/TDM, la point-spread function (PSF), la taille des voxels et la technologie TEP digitale, et d’explorer si d’autres traceurs TEP pouvaient présenter un intérêt. Le but de la première partie était d’étudier les performances de la TEP/TDM au 18FDG à l’étage cervical pour la détection de la maladie ganglionnaire. Une acquisition TEP/TDM dédiée a amélioré la détection de la maladie tumorale par rapport à l’acquisition classique. L’utilisation de la PSF a permis de détecter des tailles de lésions plus petites et la durée optimale de cette acquisition a été évaluée. Des reconstructions avec des tailles de voxels ultra-fines ont été réalisées sur TEP digitale pour étudier l’impact de la PSF et des voxels ultra-fins sur les données quantitatives. La seconde partie a porté sur l’imagerie 131I-TEMP/TDM et 18FDG-TEP/TDM, afin de quantifier le volume de la maladie persistante. Il a ainsi été montré que la masse tumorale était corrélée au risque post-opératoire et avait un impact sur la réponse au traitement. L’objectif de la troisième partie était d’étudier un autre traceur TEP, la 18-Fluorocholine (FCH), ainsi qu’un marqueur de la néovascularisation, l’antigène membranaire spécifique de la prostate (PSMA). Nos données suggèrent qu’un examen TEP à la FCH négatif au sein d’un nodule thyroïdien à cytologie indéterminée permettrait d’éliminer la malignité, et pourrait éviter des chirurgies inutiles. Par ailleurs, le marquage au PSMA évalué par immunohistochimie dans les néo-vaisseaux est associé à des facteurs de mauvais pronostic. D’autres études sont nécessaires pour confirmer l’intérêt éventuel des examens TEP à la FCH et au 68Ga-PSMA en oncologie thyroïdienne<br>Radioiodine (131I) and 18-Fluorodeoxyglucose (18FDG) are two radiopharmaceuticals used for scintigraphic imaging in differentiated thyroid cancers (DTC). Tumour uptake of each tracer depends on tumour differentiation and aggressiveness. Our goal was to further assess various technical aspects in DTC imaging workup, such as SPECT/CT and PET/CT, point-spread function (PSF), voxel size, digital PET, and to explore further other PET tracers. The aim of the first part was to assess the performance of 18FDG PET/CT for the detection of neck lymph node involvement. A dedicated PET/CT acquisition improved tumour detection compared to the whole-body acquisition. PSF reconstruction allowed detection of smaller cancer deposits and the optimal acquisition duration time was assessed. Using digital PET acquisitions, ultra-thin voxels reconstructions were performed. The impact of ultra-thin voxels and PSF on quantitative values was evaluated. The second part focused on 131I-SPECT/CT and 18FDG-PET/CT imaging, in an attempt to assess tumour burden of persistent disease. Tumor burden was correlated with the postoperative risk and affected the response to therapy. In the third part, another PET tracer, i.e. 18-Fluorocholine (FCH), and a marker of neovasculature, i.e. prostate-specific membrane antigen (PSMA), were studied. FCH PET/CT offered high negative predictive value to reliably exclude cancer in PET-negative nodules with indeterminate cytology and might prevent unnecessary surgeries. Also, PSMA expression assessed with immunohistochemistry was associated with poor prognosis factors. Further studies are needed to confirm new insights of FCH PET and 68Ga-PSMA PET in DTC
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Su, Yu-Chieh, and 蘇裕傑. "High Dose Chemotherapy followed by Autologous Peripheral Stem Cell Transplantation in Patients with Metastatic Cancer and Hematological Malignancy — A Single Institute’s Experience and Result Analysis." Thesis, 2003. http://ndltd.ncl.edu.tw/handle/03748394885187779628.
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碩士<br>高雄醫學大學<br>醫學研究所<br>91<br>There has been a dramatic increase in the number of autologous peripheral blood stem cell transplants (PBSCT) over the last decade. Faster recovery of cell counts, lesser transplant morbidity, shorter hospital stay and reduced cost compared with marrow autografts have been the main advantages. Numerous clinical trials demonstrated improved outcome using HDCT with autologous PBSCT in non-Hodgkin’s lymphoma (NHL). But there are few reports evaluating the role of HDCT with autologous PBSCT in metastatic nasopharyngeal carcinoma (NPC). Here we report our experience in HDCT with autologous PBSCT in 37 cases included 12 NHL patients, 10 metastatic NPC patients and 15 other metastatic solid tumor patients. Our results revealed that, the treatment-related mobility and mortality is not frequent. And the treatment seemed to be benefit for NHL patients who are at first remission or second remission. But in NPC and other solid tumor, our results revealed that HDCT with ICE regimen then autologous PBSCT do not prolong the overall survival and do not produce major response to these patients.
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Chang, Shao-En, and 張韶恩. "AAD01 reduces tumor hypoxia by increasing tissue perfusion in high grade malignant gliomas." Thesis, 2010. http://ndltd.ncl.edu.tw/handle/04381384016067650565.
Full textAbstract:
碩士<br>國立陽明大學<br>腦科學研究所<br>98<br>Background: Intra-tumoral hypoxia is associated with malignant progression, tumor invasion and resistance to radiotherapy and chemotherapy of cancers. Anti-angiogenic therapies targeting the vascular endothelial growth factor (VEGF) / VEGF receptor (V EGFR) have shown therapeutic effect for malignant tumors. However, they also increase intra-tumoral hypoxia. Anti-angiogenic drug 01 (AAD01), on the other hand, targets endothelial cells directly. Tetramethylpyrazine (TMP) decreased the expression of VEGF and reduced angiogenesis. This study would test these two drugs to decrease tumor hypoxia in malignant gliomas in rat.
Hypothesis: It is hypothesized that by limiting the rapid proliferation of endothelial cells, AAD01 increase tissue perfusion in gliomas, which in turn result in the decrease of intra-tumoral hypoxia. This study has also evaluated if TMP has similar effect.
Materials and Methods: Suspended 1x107 C6 glioma cells were implanted intracerebrally of the adult female Sprague-Dawley rats. The treatment group received AAD01 (10 µg / every 3 days) or TMP (2.4 mg/day, for 7 days) beginning for the 5th day. At day 13, animals were sacrificed. Tumor hypoxia and angiogenic factors were analyzed by immunohistochemistry and quantified by Western blot. Multiple groups were analyzed by one-way analysis of variance (ANOVA). P-value of less than 0.05 was considered significant.
Results: In the AAD01 treated group, tumor size was decreased (60.42%). These rats also showed less body weight loss. The expression of hypoxic inducible factor-1 α (HIF-1α) and VEGF both decreased significantly in the treatment group than in control group. The sprouting vessel, which is evaluated by staining of VEGFR2 was inhibited in the AAD01 group. The density of total vessels was decreased. The contrast, the density of perfused vessels was increased. The peri-tumor infiltration was less prominent in the AAD01 group. On the hand, the expression of HIF-1α and VEGF in the TMP group was decreased but less effect than AAD01 group. The density of perfused vessels was not significant statistically different from control.
Conclusion: AAD01 reduced tumor hypoxia by increasing tissue perfusion. Otherwise, it can reduce peri-tumor infiltration.
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Chen, Li-chiu, and 陳麗秋. "Identification of serum tumor markers for malignant disease using high-throughput proteomic technologies." Thesis, 2004. http://ndltd.ncl.edu.tw/handle/73930771765341250337.
Full textAbstract:
碩士<br>長庚大學<br>醫學生物技術研究所<br>92<br>Background: Malignant tumors are at the top leading cause of death in Taiwan in the past decades. Currently, there is no serum marker for detecting oral or nasopharyngeal cancers (ORC or NPC), neither available serum marker with high sensitivity and specificity for breast, lung, and prostate cancers (BC, LC, and PC).
Methods: Affinity purification with magnet beads and MALDI-TOF mass spectrometry analysis were used to screen and identify potential serum tumor markers for BC, LC, PC, ORC, and NPC. Compiled protein profile of each cancer group was compared to normal samples, and the differential spectra were statistically analyzed using bioinformatic softwares.
Results: Since Cu bead can discriminate most differential spectra between normal and tumor group, it was used for protein profiling. Among the five tested malignant diseases except breast cancer, several markers with high sensitivity (>80%) and specificity (>90%) were found. They are 4 LC-specific markers with molecular weight of 2878±5, 3809±5, 4975±5, and 8610±5; 2 PC-specific markers with molecular weight of 1892±5 and 2022±5; 1 ORC-specific marker with molecular weight of 2664±5; and 1 NPC-specific marker with molecular weight of 2020±5. After combination of two NPC-specific markers, the detecting sensitivity was greatly increased (94%0. Finally, two most sensitive and specific markers were identified with a PC and NPC marker (2020 Da) and an ORC marker (2658 Da). They are complement C3 precursor and alpha fibrinogen, respectively.
Conclusion: High-throughput proteomic approach could greatly facilitate the discovery of novel and better serum markers. 4 LC-specific markers, 2 PC-specific markers, 1 ORC-specific marker and 1 NPC-specific marker were found. The high specificity and sensitivity achieved by the use of these tumor-specific markers show great potential for the detection of the malignant diseases.
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Hung, Tsui Lien, and 洪翠蓮. "The underlying mechanisms of high invasiveness in tumor cells from lung cancer patients with malignant pleural effusion." Thesis, 2001. http://ndltd.ncl.edu.tw/handle/52852434576744912387.
Full textAbstract:
碩士<br>國立成功大學<br>分子醫學研究所<br>89<br>Non-small cell lung cancer (NSCLC) associated with malignant pleural effusion (MPE) is a common presentation of lung cancer in Taiwan. The major histological classification of this entity is adenocarcinoma. Microscopically, the patients’ pleurae were infiltrated by numerous tumor foci, which suggests that the adenocarcinoma cells are highly invasive. Among the NSCLC, lung adenocarcinom also has the highest incidence of distant metastasis. Because the malignant pleural effusion is closely related to lung adenocarcinoma and it is easily obtained, we tried to analyze factors those may contribute to the aggressive behavior of lung adenocarcinoma within the pleural fluids. The factors we chose were: CD44, several growth factors, IL-6, MMP family, PA system and some oncoproteins. Pleural fluids were obtained from patients with lung adenocarcinom, pulmonary tuberculosis (TB), empyema, parapneumonia and congestive heart failure. We found that the expression of Her2/neu and IGF-1 were significantly higher in lung adenocarcinoma group than the expression in other groups. The expression of uPA, uPAR, PAI-1, PAI-2, VEGF and IL-6 were higher in lung adenocarcinoma group than heart failure group. As a tumor marker for differentiation between malignant and non-malignant effusion, the diagnostic performances of Her2/neu, IGF-1 and Cyfra 21-1 are equally well. However, the expression of Her2/neu and IGF-1 is more related to tumor biology, therefore, we believe that Her2/neu and IGF-1 are better tumor markers than the conventional ones. Beside the demonstration of their clinical potential in the future, we have also studied the synergistic interaction between IGF-1 and Her2/neu. IGF-1 induced migration and invasion of PC14PE6-T1 and -AS2 cells, derived from cells in malignant pleural effusion of a patient with lung adenocarcinom. The above activities of IGF-1 were inhibited by adding IGF-1R blocking antibody, suggested the induction is IGF-1R dependent. For the interaction between IGF-1/IGF-1R and Her2/neu, we found that phosphorylation of Her2/neu was induced by treating cells with IGF-1, and cellular migration induced by IGF-1, could be abolished by the Her2/neu blocking antibody-Herceptin. The results suggest IGF-1 and Her2/neu working together to enhance invasiveness of lung adenocarcinom cells.
In the current study, we have identified several factors those may contribute to the aggressiveness of lung adenocarcinoma. We have also demonstrated that Her2/neu and IGF-1 could be ideal tumor markers. Our further studies have disclosed the synergistic interaction between IGF-1 and Her2/neu. We expect these findings will have important impacts on the management of lung adenocarcinoma in the future.
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Chen, Shao-Ching, and 陳少卿. "Risk Factors Associated with the Progression of Pre-malignant Oral Lesion and Oral Cancer: A Screening Project in High-risk Group." Thesis, 2001. http://ndltd.ncl.edu.tw/handle/00620268438093399814.
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碩士<br>國立臺灣大學<br>流行病學研究所<br>89<br>Background: The impacts of the duration and the quantity of betel nuts, cigarettes, and alcohol on the disease natural history of oral pre-malignancy and economic aspect of oral cancer screening in betel nuts user have not been fully addressed.
Objectives: The purposes of this study are therefore (1) to quantify the impact of the duration and the quantity of betel nut, cigarette and alcohol on different oral pre-malignancy and transition parameters between states with respect to the disease natural history; and (2) to perform cost-effectiveness analysis for oral cancer screening.
Methods: An oral screening project for subjects with the habit of chewing betel nuts was conducted between 1998 and 1999. Oral pre-malignant lesions and oral cancer were screened by well-trained dentists. Information on socio-demographic characteristics, the duration and the quantity of betel nuts, cigarettes, and alcohol was collected by questionnaire. The disease natural history from normal, through leukoplakia and erythroplakia, and finally to oral cancer was constructed. Generalized logit model, proportional odds model and the stochastic model were adopted to elucidate factors affecting the disease natural history. Cost-effectiveness was also performed to assess different oral screening regimes.
Findings: (1) The duration and the quantity of betel nuts, to a larger extent, and smoking, to a lesser extent, play respective important roles in the development of oral pre-malignancy even after adjustment for demographic characteristics and three risk factors in each other. However, the impact of alcohol on the risk for oral pre-malignancy disappears after controlling for significant confounders such as betel nuts and smoking. The risk for leukoplakia, erythroplakia, and OSF is proportional to the quantity and the duration. The adjusted odds ratios for subjects chewing more than 20 pieces per day against occasional use were estimated as 5.5 (95%CI: 3.9-7.8), 38.4 (95% CI: 16.7-88.1), and 7.1 (95% CI: 5.1-9.9) for leukoplakia, erythroplakia, and OSF, respectively. (2) The average times from leukoplakia to erythroplakia and from erythroplakia to invasive carcinoma take around 20 years and 5.7 years, respectively. Taking the quantity into account, the average times from leukoplakia to erythroplakia were 27.3 yrs, 24.0 yrs, 15.3yrs, and 13.1 yrs. The similar results were also found while the duration is considered. (3) The incremental cost-effectiveness ratios for annual screening regime, five-yearly screening regime, 10-yearly screening regime, against the control group were calculated as $21.59, $36.34, $5.32 per life-year gained.
Conclusion: The impact of the quantity and the duration betel nuts, cigarette, and alcohol on disease natural history are quantified. Cost-effectiveness analysis for four screening regimes suggests that 10-year screening regime may be appropriate for this high-risk group.
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CHEN, YI-WEN, and 陳怡文. "High Folic Acid Supplementation Reprograms The Bioenergetics Mechanism of Lactate Metabolic Microenvironment to Promote The Malignant Progression in Non-small Cell Lung Cancer." Thesis, 2019. http://ndltd.ncl.edu.tw/handle/4t8vj9.
Full textAbstract:
碩士<br>輔仁大學<br>營養科學系碩士班<br>107<br>Lung cancer is the leading cause of cancer deaths in Taiwan, and of which 85% is non-small cell lung cancer (NSCLC). The five-year survival rate of lung cancer patients with metastasis is less than 10%. Studies showed that the poor prognosis of lung cancer patients was mainly due to highly invasion and metastasis. It was known that malignant tumors were viewed as cancer stem cell (CSC) metabolic variability diseases, and CSCs were involved in regulating epithelial-mesenchymal transition (EMT), invasion, metastasis, and chemotherapy resistance. Tumor cells underwent anaerobic glycolysis to accumulation lactate to obtain energy through a unique metabolic method "Warburg effect", and acidulate the tumor microenvironment. It induced energy metabolic switch to promote invasion and metastasis in CSCs. Nowadays, the clinical therapy strategy of lung cancer is treated with folate supplementation and chemotherapeutic drugs. The impact of high folate nutrition status on CSCs formation and the bioenergetics mechanism in malignant tumor cells is still unclear. Therefore, the aim of this study is to explore high folic acid supplementation reprograms the bioenergetics mechanism of lactate metabolic microenvironment to promote the malignant progression in non-small cell lung cancer. The study design included animal model and cell culture. Six-week-old C57BL/6 male mice were fed with control diet ( 2 mg/kg folic acid ) and high folate supplement diet (8 mg/kg folic acid) plus folate supplement water ( 8 mg/ml folic acid ) for 14 days prior to the intrapleural injection with Lewis lung cancer spheroid cells or saline. After 9 days, mice were sacrificed and analyzed blood and lung tissue. The results showed that high folic acid supplement with metastatic cancer cells increased circulating lactate and glucose level to induce malignant progression in lung tissue. Human NSCLC cells A549 were cultured in control medium ( 2.2 μM folic acid ) or high FS medium ( 10, 30, 50 μM folic acid ) for 2 to 4 days. After treatment, cells were harvested to explore the self-renewal capacity and bioenergetics metabolism switch. The results showed that high FS microenvironment presented increased AMPK and PI3K signaling pathway, higher HKII and LDHA protein expression, lower MCT4 and GLUT1 protein expression, increased NADH/NAD+ and NADPH/NADP+ ratio. It induced abnormal glucose metabolism and cellular lactate accumulation to promote CSCs formation and malignant metastasis in NSCLC. In conclusion, the results indicated that high FS microenvironment reprograms lactate-generating metabolism to promote in vitro stemness and in vivo malignant progression of NSCLC.