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Salivary gland tumours: a combined morphometric, flow cytometric and immunohistochemical analysisZhu, Qianru, 朱茜如 January 1998 (has links)
published_or_final_version / Anatomy / Doctoral / Doctor of Philosophy
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Tumor targeting with a ⁹⁹̳mTcMAG-3 labeled molecular engineSlauson, Marjorie E. 08 February 2006 (has links)
A unique tumor targeted method, which may be able to deliver a molecule to the
surface of a tumor cell using the pH gradient between hypoxic tumor cells and
normal tissue has recently been developed. Since solid tumors have been found to
have a lower extra cellular pH compared to normal tissue (6.5 to 6.9 for tumors
verses an average 7.4 for normal tissue), the pH gradient is used as a source of
power to activate a strategically designed "molecular engine" capable of delivering
a diagnostic or therapeutic agent to tumor cells. To test this hypothesis, a 22-
sequence amino acid, which reorganizes to alpha helical form at pH 6.9 causing
the molecule to become lipophilic and embed into the plasma membrane of nearby
cells was synthesized. The molecule was then attached to 99mTc via a MAG-3
chelating molecule. In-vivo nuclear imaging was performed and showed apparent
significant uptake in primary tumors as well as lung and liver in Lewis lung cell
model C57blk-J6 mice with confirmed primary tumors at the base of the tail or
lungs. This study shows significant promise for early diagnosis and treatment of
cancer on a molecular level. / Graduation date: 2006
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Magnetic resonance imaging of sodium and its application黃嘉冠, Wong, Ka-kwun, Kelvin. January 2000 (has links)
published_or_final_version / Electrical and Electronic Engineering / Master / Master of Philosophy
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Statistical decision making with a dual detector probe.Hickernell, Thomas Slocum. January 1988 (has links)
Conventional imaging techniques for cancer detection have difficulty finding small, deep tumors. Single-detector radiation probes have been developed to search for deep lesions in a patient who has been given a tumor-seeking radiopharmaceutical. These probes perform poorly, however, when the background activity in the patient varies greatly from site to site. We have developed a surgical dual-detector probe that solves the problem of background activity variation, by simultaneously monitoring counts from a region of interest and counts from adjacent normal tissue. A comparison of counts from the detectors can reveal the class of tissue, tumor or normal, in the region of interest. In this dissertation we apply methods from statistical decision theory and derive a suitable comparison of counts to help us decide whether a tumor is present in the region of interest. We use the Hotelling trace criterion with a few assumptions to find a linear discriminant function, which can be reduced to a normalized subtraction of the counts for large background count-rate variations. If area under the ROC curve is our figure of merit, the likelihood ratio is the optimum discriminant. We model likelihood functions of the data given the "tumor" and "no-tumor" hypotheses, and calculate the likelihood ratio. Using a spatial response map of the dual probe, a computer torso phantom, and estimates of activity distribution, we simulate a surgical staging procedure to test the dual probe and the discriminant functions. Results of the simulations show that the dual probe effectively solves the problem of background activity variations when used with any of the discriminant functions derived in this dissertation.
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Assessment of CD44 and K19 as markers for circulating breast cancer cells using immunobead RT-PCR / by Michael Campbell Eaton.Eaton, Michael Campbell January 1997 (has links)
Includes bibliographies. / [xvii], 173, [38] leaves, [18] leaves of plates : / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / This thesis presents the development of an assay for reverse transcription-polymerase chain reaction (RT-PCR) to be applied to the immunomagnetic isolation of carcinoma cells, as a possible means of detecting small numbers of breast cancer cells in a haemopoietic environment. The messenger RNA expression of two different genes, CD44 and the cytokeratin K19, is assessed for suitability as tumour markers for the Immunobead RT-PCR method, and clinical results using K19 are presented. / Thesis (M.D.)--University of Adelaide, Dept. of Medicine, 1977?
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The development and evaluation of molecular biological techniques to detect solid tumour cells in peripheral blood / Kenneth Brian Pittman.Pittman, Kenneth Brian. January 1995 (has links)
Erratum is pasted onto back endpaper. / Bibliography: leaves 189-219. / xxiii, 221 leaves : / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Current understanding of metastatic processes and the clinical significance of these processes is discussed. The study of circulating solid tumour cells in peripheral blood is reviewed from an historical perspective. Newer molecular and cell biological techniques which may facilitate more reliable tumour evaluation are reviewed with special reference given to polymerase chair reaction (PCR) / Thesis (M.D.)--University of Adelaide, Dept. of Surgery, 1997?
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Fine needle aspiration cytology in the study of neck massChen, Xiuyun. January 2003 (has links)
published_or_final_version / Medical Sciences / Master / Master of Medical Sciences
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The development and evaluation of molecular biological techniques to detect solid tumour cells in peripheral blood / Kenneth Brian Pittman.Pittman, Kenneth Brian. January 1995 (has links)
Erratum is pasted onto back endpaper. / Bibliography: leaves 189-219. / xxiii, 221 leaves : / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Current understanding of metastatic processes and the clinical significance of these processes is discussed. The study of circulating solid tumour cells in peripheral blood is reviewed from an historical perspective. Newer molecular and cell biological techniques which may facilitate more reliable tumour evaluation are reviewed with special reference given to polymerase chair reaction (PCR) / Thesis (M.D.)--University of Adelaide, Dept. of Surgery, 1997?
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Machine learning for systems pathologyVerleyen, Wim January 2013 (has links)
Systems pathology attempts to introduce more holistic approaches towards pathology and attempts to integrate clinicopathological information with “-omics” technology. This doctorate researches two examples of a systems approach for pathology: (1) a personalized patient output prediction for ovarian cancer and (2) an analytical approach differentiates between individual and collective tumour invasion. During the personalized patient output prediction for ovarian cancer study, clinicopathological measurements and proteomic biomarkers are analysed with a set of newly engineered bioinformatic tools. These tools are based upon feature selection, survival analysis with Cox proportional hazards regression, and a novel Monte Carlo approach. Clinical and pathological data proves to have highly significant information content, as expected; however, molecular data has little information content alone, and is only significant when selected most-informative variables are placed in the context of the patient's clinical and pathological measures. Furthermore, classifiers based on support vector machines (SVMs) that predict one-year PFS and three-year OS with high accuracy, show how the addition of carefully selected molecular measures to clinical and pathological knowledge can enable personalized prognosis predictions. Finally, the high-performance of these classifiers are validated on an additional data set. A second study, an analytical approach differentiates between individual and collective tumour invasion, analyses a set of morphological measures. These morphological measurements are collected with a newly developed process using automated imaging analysis for data collection in combination with a Bayesian network analysis to probabilistically connect morphological variables with tumour invasion modes. Between an individual and collective invasion mode, cell-cell contact is the most discriminating morphological feature. Smaller invading groups were typified by smoother cellular surfaces than those invading collectively in larger groups. Interestingly, elongation was evident in all invading cell groups and was not a specific feature of single cell invasion as a surrogate of epithelialmesenchymal transition. In conclusion, the combination of automated imaging analysis and Bayesian network analysis provides an insight into morphological variables associated with transition of cancer cells between invasion modes. We show that only two morphologically distinct modes of invasion exist. The two studies performed in this thesis illustrate the potential of a systems approach for pathology and illustrate the need of quantitative approaches in order to reveal the system behind pathology.
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Identification and validation of new markers and potential therapeutic targets for gastrointestinal stromal tumors in murine models and in human pathological materialGromova, Petra 09 June 2011 (has links)
Les tumeurs gastro-intestinales stromales (Gastro-Intestinal Stromal Tumours - GIST en Anglais) sont les sarcomes les plus fréquents du tube digestif. Sur base de leur profil d'expression génique et de similitudes morphologiques, il a été établi que les GIST dérivent des cellules interstitielles de Cajal (Interstitial Cells of Cajal - ICC en Anglais) ou d'un précurseur commun. Le développement et le maintient des ICC sont dépendant de voies de signalisation du récepteur tyrosine kinase KIT. Des mutations oncogéniques de KIT, conduisant indépendamment du ligand à l'activation des voies de signalisation en aval, sont présentes dans environ 85% des GIST. Depuis une dizaine d'années, des molécules de synthèse qui inhibent la phosphorylation -et donc l'activation - de KIT ont été introduites avec succès dans le traitement clinique des GIST. Cependant des résistances, souvent causées par des mutations secondaires, apparaissent fréquemment et environ 50% des patients traités rechutent dans les 2 ans. Le développement de nouvelles stratégies diagnostiques et thérapeutiques pour les GIST demeure donc essentiel. Ces dernières années, de nouveaux marqueurs diagnostiques ou cibles thérapeutiques potentielles ont été rapportés dans la littérature (p.ex. Discovered on GIST-1 (DOG1, anoctamin 1), Protein kinase C theta (PKC theta), Carbonic anhydrase II (CAII)) .Il faut relever que tous ces gènes sont aussi exprimés par les ICC KIT+ du tube digestif normal et que leur présence dans les GIST reflète donc vraissemblablement essentiellement leur parenté avec les ICC.<p>Dans la présente étude, nous nous sommes attachés à identifier de nouveaux marqueurs diagnostiques ou cibles thérapeutiques potentielles exprimés par les GIST mais absent des ICC KIT+ normales.<p>Pour ce faire, nous avons comparé le profile d'expression géniques de l'antre gastrique de souris porteuses de la mutation oncogénique Kit K641E et de souris contrôles (wild type WT en Anglais) par la technique de cDNA microarray. Les différences d'expression génique ont été ensuite confirmées par réactions de PCR quantitative (qPCR) en temps réel et l'immunoréactivité (-ir) pour les candidats les plus prometteurs a été localisée par immunofluorescence (IF) dans la muscularis propria du tube digestif, avec une attention spéciale pour les cellules KIT+.<p>Plusieurs gènes identifiés appartenaient tant au profil d'expression génique des GIST qu'au profil d'expression des ICC Kit+ de l'intestin grêle murin, validant ainsi la pertinence du modèle murin KitK641E pour l'approche choisie (Chapitre 3). D'autre part, trois gènes identifiés (Neurotensin receptor 1 (Ntsr1), Trophoblast glycoprotein (Tpbg/5T) et Sprouty homolog 4 (Spry4)) étaient quant à eux présents dans la couche hypertrophié de cellules Kit+ de l'antre des souris KitK641E mais absentes des ICC Kit+ chez les souris WT (Chapitres 3, 4, 5). Ces gènes représentant donc de nouveaux candidats potentiels comme marqueurs spécifiques et/ou comme cibles thérapeutiques dans les GIST, nous avons, dans la seconde partie de notre travail, approfondi l'étude de leur expression et de leur régulation en utilisant des modèles cellulaires et tissulaires murins, ainsi que du matériel anatomopathologique de GIST humains.<p>Dans le tube digestif normal, NTSR1 et TPBG/5T4 ir ont été identifiés dans les neurones myentériques mais pas dans les ICCKIT+. Deux "tissue arrays" indépendants, totalisants 97 spécimens humains de GIST, ont révélés la présence de NTSR1-ir dans tous les GIST, en ce compris les cas négatifs pour KIT, tandis que TPBG/5T4-ir était présente dans 36/49 GIST. Un fort immunomarquage pour TPBG/5T4 était statistiquement associée aux tumeurs malignes et de haut risque (Chapitre 5; Annexe 1).<p>L'expression différentielle de membres de la famille des "Sprouty homologues" (Spry) dans l'antre des souris KitK641E a aussi été identifiée. Spry4-ir n'était pas détectable dans les ICC KIT+ des souris WT alors que Spry4-ir était présente dans la couche hyperplasique des cellules Kit+ chez les souris KitK641E. A l'opposé, l'ARN messager de Spry2 présentait un niveau d'expression similaire et Spry2-ir était détectée dans les cellules musculaires lisses - mais pas dans les cellules Kit+ - dans tous les génotypes (Chapitre 3). Pour sa part, l'expression de Spry1 apparaissait réprimée par le mutant oncogénique KitK641E, tant in vivo qu'in vitro, conduisant à la dérégulation de la boucle de rétrocontrôle négatif de la voie Ras/Erk (Chapitre 4). <p>Dans la dernière partie de cette thèse, nous avons étudié l'expression Endoglin (ENG) - aussi connues sous le nom de CD105 – dans le modèle murin de GIST KitK641E, dans les GIST humains et dans le modèle cellulaire murin Ba/F3 in vitro. ENG est une glycoprotéine transmembraire et un composant auxiliaire du complexe du récepteur au TGF-& / Doctorat en Sciences biomédicales et pharmaceutiques / info:eu-repo/semantics/nonPublished
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