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1
Tumar, Iyad [Verfasser]. „Resource Management of Disruption Tolerant Networks / Iyad Tumar“. Aachen : Shaker, 2011. http://d-nb.info/1081884959/34.
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2
Das, Sanjib Kumar. „Characterization of Tumar infiltrating lymphocytes in marine sarcoma and their role in curbing malignancy“. Thesis, University of North Bengal, 1997. http://hdl.handle.net/123456789/1006.
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Svanberg, Frida, und Timothy Shen. „EN FÖRÄNDRAD IDENTITET : Sexualitetens påverkan i samband med bröstcancer. En litteraturöversikt“. Thesis, Högskolan i Skövde, Institutionen för hälsa och lärande, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:his:diva-10471.
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Bakgrund: I Sverige drabbas 8000 kvinnor av bröstcancer varje år. Dessa kvinnor utsätts för både kroppsliga och emotionella biverkningar och förändringar. Syfte: Syftet med denna litteraturöversikt är att belysa hur kvinnor som drabbas av bröstcancer upplever att deras sexualitet påverkas av sjukdom och behandling. Metod: Metoden var en litteraturstudie. Resultat: Ett huvudtema framkom en förändrad identitet; och fem subteman: kroppsliga förändringar, känna sig okvinnlig, relationens betydelse, kommunikationens betydelse för att komma vidare och sjukvårdens betydelse. Slutsats: Resultatet visade att kvinnorna upplevde att de förlorat sin sexuella identitet och sin kvinnlighet. Förlusten gjorde att de inte kunde identifiera sig med den kvinna som de tidigare varit. De upplevde flera fysiska förändringar som ledde till minskad sexuell aktivitet. Men trots den minskade sexuella aktiviteten upplevde många av kvinnorna en ökad närhet till sin partner och stödet från en partner ansågs viktigt. Många kvinnor saknade dock stöd och information från sjukvården angående sexuella problem. De upplevde att vårdpersonalen tyckte det var genant eller oviktigt att tala om kvinnornas sexualitet. Då sjuksköterskans primära mål är att främja hälsa och välbefinnande bör sjuksköterskan beakta kvinnornas sexualitet eftersom sexualiteten är en viktig dimension för upplevelsen av hälsa.Background: In Sweden 8000 women are afflicted by breast cancer every year. These women are subject to both physical and mental side effects and alternations. Aim: The objective of this literature review is to highlight how women in the case of breast cancer experience that their sexuality is affected by the disease and treatment. Method: The method is a review of the related literature. Results: One major theme emerges: a changed identity, and five minor themes: physiological changes, feeling unfeminine, the significance of relationship, the significance of communication in order to move on, and the significance of medical care. Conclusion: It turns out that these women experienced a loss of their sexual identity and their femininity. The deprival resulted in an inability to identify themselves with the women they once were. They also experienced physiological changes, e.g. dryness of the vaginal mucous membrane, pain from the removed breast, and less sexual arousal which impeded and reduced the sexual activity of the women. But despite reduced sexual activity, many of these women experienced acquiring a greater proximity to their partner, and that the support from a partner was regarded as important. Many of the women, though, lacked support and information from the medical institutions concerning sexual problems. They experienced that the medical staff thought that conversing upon the women’s sexuality was something embarrassing or of no importance. Since the primary objective of the nurse is to promote health and well-being, the nurse should take heed to and attend to the sexuality of the women, considering that sexuality is an important dimension in regard to experiencing health.
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Butler, Savannah E. „TUMOR-INTRINSIC INFLAMMATORY PATHWAYS ASSOCIATED WITH TUMOR DORMANCY AND RECURRENCE“. VCU Scholars Compass, 2017. http://scholarscompass.vcu.edu/etd/4753.
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The successful treatment of breast cancer is limited due to a fraction of tumor cells escaping drug-treatment by entering a dormant state, only to relapse years or decades later at distant sites. Host-driven chronic inflammatory cells such as M2 macrophages play an important role in tumorigenesis, but the role of tumor-intrinsic inflammatory signaling involved in tumor dormancy and recurrence is unknown. We sought to determine the role of tumor-intrinsic inflammatory pathways in mouse mammary carcinoma cells (MMC) treated with Adriamycin (ADR), a clinically relevant chemotherapeutic drug. We found that ADR-induced dormant tumor cells autonomously produced pro-inflammatory cytokines, in vitro. MMC treated with Chloroquine (CQ) prior to ADR treatment displayed a delay in relapse, or prolonging of dormancy, when compared to ADR-treated MMC. Additional gene array data showed predicated activation of NF-κB p65 in ADR-treated dormant MMC that eventually relapsed. These data suggest that the anti-inflammatory function of CQ led to prolonged dormancy. To test this, we investigated the role of inflammatory signaling pathways directly by shRNA-mediated knockdown and CRISPR-Cas9-mediated knockout of NF-κB p65 in MMC. We found that knockdown of NF-κB p65 resulted in fewer dormant cells after ADR treatment and reduced rate of relapse, in vitro. NF-κB p65 was also found to reduce the immunomodulatory effects of ADR, with shNF-κB p65 showing increased upregulation of neu upon ADR treatment. Additionally, we found NF-κB p65 to be associated with a higher infiltration of CD8+ T cells and anti-tumor T cell responses. Our findings suggest a dual role of tumor-intrinsic NF-κB p65 pathway, allowing for escape from drug treatment through dormancy which leads to relapse, but also for proper lymphocyte infiltration and subsequent anti-tumor activity.
5
Casiraghi, Nicola. „Quantitative analyses to study tumor clones dynamics and tumor heterogeneity“. Doctoral thesis, Università degli studi di Trento, 2017. https://hdl.handle.net/11572/368498.
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Prostate cancer is a highly heterogeneous disease and its manifestations can vary from indolent localized tumor to widespread metastases. This heterogeneity is also observed at the molecular level both inter- and intra-patient. Intra-patient heterogeneity in the clinical setting of men with castration resistant prostate cancer (CRPC) might be informative in terms of treatment decision. Here I present analytical work on two approaches relevant to the characterization of intra-patient heterogeneity and applied to unpublished CRPC patients sequencing data. The first is based on the genome wide interrogation of multiple metastatic and primary tissue biopsies from single patients. I present genomic analyses to decipher the content of multiple tumor biopsies from CRPC patients and provide comparisons to highlight similarities and differences and to identify alternative patterns of aberrations. The second approach, alternative to tissue biopsies that might under-represent the genomic landscape of the patient’s disease, relies on liquid biopsies, a minimally invasive test that is also amenable to serial sampling. Liquid biopsies contain circulating cell free DNA (cfDNA) released from widespread tumor cells, potentially uncovering the full tumor landscape. By using next generation sequencing on cfDNA obtained from plasma, I developed strategies aimed at systematically tracking the reiterative process of genetic diversification leading to disease evolution and to detect genomic aberrations. I specifically focused on an ad hoc computational procedure (ABEMUS) to detect somatic point mutations that could emerge under treatment pressure and as drug resistance mechanism. The work I present is relevant to the context of precision oncology that exploits detailed patient-specific molecular information to diagnose and follow cancer progression with the ultimate goal of promptly guiding treatment decisions to improve clinical outcome with transdisciplinary strategies. The analytical work I developed can be applied to the study of any tumor type.
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Casiraghi, Nicola. „Quantitative analyses to study tumor clones dynamics and tumor heterogeneity“. Doctoral thesis, University of Trento, 2017. http://eprints-phd.biblio.unitn.it/2626/2/Disclaimer_Casiraghi.pdf.
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Prostate cancer is a highly heterogeneous disease and its manifestations can vary from indolent localized tumor to widespread metastases. This heterogeneity is also observed at the molecular level both inter- and intra-patient. Intra-patient heterogeneity in the clinical setting of men with castration resistant prostate cancer (CRPC) might be informative in terms of treatment decision. Here I present analytical work on two approaches relevant to the characterization of intra-patient heterogeneity and applied to unpublished CRPC patients sequencing data. The first is based on the genome wide interrogation of multiple metastatic and primary tissue biopsies from single patients. I present genomic analyses to decipher the content of multiple tumor biopsies from CRPC patients and provide comparisons to highlight similarities and differences and to identify alternative patterns of aberrations. The second approach, alternative to tissue biopsies that might under-represent the genomic landscape of the patient’s disease, relies on liquid biopsies, a minimally invasive test that is also amenable to serial sampling. Liquid biopsies contain circulating cell free DNA (cfDNA) released from widespread tumor cells, potentially uncovering the full tumor landscape. By using next generation sequencing on cfDNA obtained from plasma, I developed strategies aimed at systematically tracking the reiterative process of genetic diversification leading to disease evolution and to detect genomic aberrations. I specifically focused on an ad hoc computational procedure (ABEMUS) to detect somatic point mutations that could emerge under treatment pressure and as drug resistance mechanism. The work I present is relevant to the context of precision oncology that exploits detailed patient-specific molecular information to diagnose and follow cancer progression with the ultimate goal of promptly guiding treatment decisions to improve clinical outcome with transdisciplinary strategies. The analytical work I developed can be applied to the study of any tumor type.
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Diego, Ángeles Pedro, Ximena Vega und José Palacios. „Tumor mucoso apendicular“. Asociación Colombiana de Cirugía, 2016. http://hdl.handle.net/10757/615473.
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Los tumores mucosos apendiculares tienen baja incidencia y comúnmente se diagnostican en el estudio anatomo-patólogico después de la apendicectomía.
Se reporta el caso de una mujer de 41 años de edad, con un cuadro clínico de ocho meses de evolución, caracterizado por dolor abdominal de tipo opresivo, difuso y de gran intensidad en el hemiabdomen inferior, acompañado de náuseas. Después de cinco meses de iniciado este cuadro clínico, se evidenció una masa en la fosa iliaca derecha; el dolor se agudizó e intensificó, y las náuseas continuaron, por lo cual fue remitida al hospital.
En los exámenes practicados se observó una masa quística compleja abdomino-pélvica de origen indeterminado, y la tomografía computadorizada de abdomen fue sugestiva de mucocele apendicular. Con estos hallazgos, se optó por el tratamiento quirúrgico por laparotomía, consistente en hemicolectomía derecha, con resección parcial de íleon, epiplectomía, histerectomía y salpigooforectomía bilateral.
8
Petty, Aaron. „Novel MIG-7 expression increases tumor cell invasion and tumor progression“. Online access for everyone, 2008. http://www.dissertations.wsu.edu/Thesis/Spring2008/a_petty_040908.pdf.
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Anderson, Jeff. „Genetic Analysis Of Specialized Tumor Associated Macrophages And Tumor Associated Fibroblast“. The Ohio State University, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=osu1228083946.
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Liu, Jian. „POLYMER MODIFICATION OF FULLERENE FOR PHOTODYNAMIC TUMOR THERAPY AND TUMOR IMAGING“. 京都大学 (Kyoto University), 2010. http://hdl.handle.net/2433/120886.
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Quang, Ly. „Photosensitizing effects of M-Tetrahydroxypheylchlorin on human tumor xenografts : correlation with sensitizer uptake, tumor doubling time and tumor histology /“. [S.l.] : [s.n.], 1999. http://www.ub.unibe.ch/content/bibliotheken_sammlungen/sondersammlungen/dissen_bestellformular/index_ger.html.
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Kim, Jungho. „Involvement of WT1 tumor suppressor gene in desmoplastic small round cell tumor“. Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape2/PQDD_0034/NQ64587.pdf.
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Kim, Jungho 1964. „Involvement of WT1 tumor suppressor gene in desmoplastic small round cell tumor“. Thesis, McGill University, 1999. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=36621.
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The transformation process involves genetic changes to cellular protooncogenes and tumor suppressor genes. The consequences of these genetic alterations are to confer a growth advantage to the cell. Three genetic mechanisms activate oncogenes or inactivate tumor suppressor genes in human neoplasms: (i) mutations, (ii) gene amplification, and (iii) chromosomal rearrangements. In many human cancers, tumor-specific chromosomal rearrangements are known to create chimeric products with the ability to transform cells. The EWS/WT1 protein is such a fusion product, resulting from a t(11;22) chromosomal translocation in Desmoplastic Small Round Cell Tumor (DSRCT), where 265 amino acids from the amino terminus of Ewing's sarcoma protein (EWS) are fused to zinc fingers II--IV of WT1. WT1 is a tumor suppressor gene expressed in the developing and adult urogenital system. Inactivation of WT1 has been correlated with initiation of Wilms' tumor (WT), a pediatric nephroblastoma, and Denys-brash syndrome, which is characterized by severe genitourinary disorders and WT. WT1 encodes a zinc-finger transcription factor belonging to the EGR (early growth response) family of Cys2-His2 zinc finger proteins and is mutated in 5--15% of sporadic WTs. WT1 recognizes the GC-rich motif, 5'-GCGGGGGCG-3 ', as well as a (TCC)n motif, albeit with different affinities, and can affect expression of a number of genes involved in the regulation of cell proliferation or differentiation. The t(11;22)(p13;g12) chromosomal translocation involved in DSRCT produces a chimeric protein containing the potential transcriptional activation domain of EWS fused to the DNA binding domain of WT1, suggesting that it may recognize similar DNA sequences as WT1. Since the DNA binding domains of WT1 and EWS/WT1 are structurally different, we have assessed the functional consequences of the EWS/WT1 fusion. We find that the EWS/WT1 protein has a higher binding affinity for the GC-rich WT1 binding site than the WT1 product
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Guarino, Brianna D. „Role of the tumor microenvironment on mechanosensitive TRPV4 channels and tumor angiogenesis“. NEOMED Integrated Pharmaceutical Medicine / OhioLINK, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=ne2mh1619702863516646.
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SACHDEVA, MOHIT. „MiR-145 is a tumor suppressor in both tumor progression and metastasis“. OpenSIUC, 2010. https://opensiuc.lib.siu.edu/dissertations/206.
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MicroRNAs (miRNAs) are non-coding small RNAs that regulate gene expression at the post-transcriptional level by interacting with the 3'-untranslated region (3'-UTR) of a target gene. Our previous studies indicate that miR-145 is downregulated in breast and colon cancer; moreover, it functions as a tumor suppressor capable of inhibiting tumor cell growth both in vitro and in vivo. In this study, we show that a putative tumor suppressor, miR-145, is regulated through the phosphoinositide-3 kinase (PI-3K)/Akt and p53 pathways. Importantly, p53 transcriptionally induces the expression of miR-145 by interacting with a potential p53 response element (p53RE) in the miR-145 promoter. We further show that c-Myc is a direct target for miR-145. Although miR-145 silences the expression of c-Myc, anti-miR-145 enhances its expression. This specific silencing of c-Myc by miR-145 accounts at least in part for the miR-145- mediated inhibition of tumor cell growth both in vitro and in vivo. Finally, the blockade of miR-145 by anti-miR-145 is able to reverse the p53-mediated c-Myc repression. Together, these results define the role of miR-145 in the posttranscriptional regulation of c-Myc by p53. in addition, we show that miR-145 exerts its growth inhibitory function in a cell-specific manner. Although miR-145 inhibits cell growth in MCF-7 and HCT-116 cells, it has no significant effect on cell growth in metastatic breast cancer cell lines. However, miR-145 significantly suppresses cell invasion in these cells; in contrast, the antisense oligo against miR-145 increases cell invasion. miR-145 is also able to suppress lung metastasis in an experimental metastasis animal model. This miR-145-mediated suppression of cell invasion is in part due to the silencing of the metastasis gene mucin 1 (MUC1). Using luciferase reporters carrying the 3′-untranslated region of MUC1 combined with Western blot and immunofluorescence staining, we identify MUC1 as a direct target of miR-145. Moreover, ectopic expression of MUC1 enhances cell invasion, which can be blocked by miR-145. Of interest, suppression of MUC1 by miR-145 causes a reduction of β catenin as well as the oncogenic cadherin 11. Finally, suppression of MUC1 by RNAi mimics the miR-145 action in suppression of invasion, which is associated with downregulation of β-catenin and cadherin 11. Taken together, these results suggest that as a tumor suppressor, miR-145 inhibits not only tumor growth but also cell invasion and metastasis.
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Chaddad, Hassan. „Development of vascularized tumor spheroids mimicking the tumor environment : angiogenesis and hypoxia“. Thesis, Strasbourg, 2019. http://www.theses.fr/2019STRAJ001.
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Le microenvironnement tumoral, l'angiogenèse tumorale et l'hypoxie jouent un rôle crucial dans la progression tumorale et le développement de thérapies de nombreux cancers. Les limites de pénétration des médicaments, les phénomènes de résistance aux anti-cancéreux, la vascularisation de la tumeur et l’hypoxie sont tous des paramètres influençant les effets du médicament. La culture cellulaire 3D permet de créer un microenvironnement qui imite l’architecture et la fonction des tissus in vivo. L’expression de gènes et de protéines modifiée par l’environnement 3D est une autre caractéristique qui impacte l’effet d’une molécule thérapeutique. Dans notre première étude, afin de développer un modèle 3D vascularisé imitant celle des tumeurs in vivo, nous avons mis en culture des cellules endothéliales en 2D avec des cellules tumorales en 3D. Après 2 semaines de culture, un réseau vasculaire s’est organisé avec des structures de type tubulaire présentant une lumière et exprimant différents marqueurs angiogéniques tels que VEGF, CD31 et Collagène IV. Dans notre deuxième étude, nous avons développé un modèle d’hypoxie in vitro intégrant l'environnement 3D et un agent mimétique de l'hypoxie (CoCl2). Le but de ce modèle est de créer un modèle d'hypoxie imitant les tumeurs in vivo et de montrer l'importance de l'hypoxie dans la réponse et la résistance aux médicaments. Ces résultats ont révélé que la meilleure condition était la combinaison 3D+CoCl2, conduisant à la surexpression des gènes relatifs à l’hypoxie (GLUT1/3, VEGF) et à la résistance aux médicaments (ABCG2, MRP1). L'angiogenèse et l'hypoxie sont des facteurs clés pour le microenvironnement tumoral in vivo et ils doivent être adoptés dans la conception de modèles tumoraux in vitro pour mieux sélectionner et cribler les médicaments anticancéreuxThe tumor microenvironment, tumor angiogenesis, and hypoxia play a critical role in the tumor progression and therapy development of many cancers. Limitations in drug penetration, multidrug resistance phenomena, tumor vascularization, and oxygen deficiency are all parameters influencing drug effects. 3D cell culture allows to create a microenvironment that more closely mimics in vivo tissue architecture and function, thus, gene and protein expression modified by the 3D environment are further features that affect treatment outcome. In our first study, in order to develop a vascularized 3D model like in vivo tumors, we co-cultured 2D endothelial cells with 3D tumor cells. After 2 weeks of this combination, a vascular network was formed and organized with tubule-like structures presenting a lumen and expressing different angiogenic markers such as VEGF, CD31 and Collagen IV. In our second study, we developed an in vitro hypoxia model integrating the 3D environment and a hypoxia mimetic agent (CoCl2) to mimic the in vivo tumors and to show the importance of hypoxia in drug response and resistance. Results revealed that the best condition was the combination 3D+CoCl2 model, leading to overexpression oh hypoxia (GLUT1/3, VEGF) and drug resistance (ABCG2, MRP1) related genes. Taken together, angiogenesis and hypoxia are key factors for in vivo tumor microenvironment and they should be adopted in in vitro model design to better select and screen anticancer drugs
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ZONARI, ERIKA. „Tumor infiltrating myeloid cells: modulators of tumor microenvironment and novel therapeutic targets“. Doctoral thesis, Università degli Studi di Milano-Bicocca, 2012. http://hdl.handle.net/10281/29814.
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Activation of a productive immune response requires transient upregulation of miR155 in the hematopoietic compartment. In order to investigate miR-155 in the context of tumor-associated immune responses, we stably knocked down (KD) miR-155 in the myeloid compartment of MMTV-PyMT mice (PyMT), a mouse model of spontaneous breast carcinogenesis that closely mimics tumor-host interactions seen in humans. Notably, myeloid cell specific miR-155 KD significantly accelerated tumor growth, as reflected by increased tumor mass and more pronounced secondary hematopoietic changes, i.e. leukocytosis and anemia. Mechanistically, miR155 KD reduces classical activation of tumor macrophages creating an imbalance towards a protumoral microenvironment as evidenced by up-regulation of the Th2 gene "IL13" in CD4+ T cells.
Our studies are one of the first to implicate a miRNA in modulating myeloid responses in the tumor microenvironment. This study further highlights the importance of tumor infiltrating hematopoietic cells in fighting cancer development and establishes an antitumoral function of a prototypical oncomir, underscoring the context-specificity of miRNA regulation.
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Vianna, Karina Costa Maia. „Tumor estomal gastrointestinal (GIST)“. reponame:Repositório Institucional da UFPR, 2012. http://hdl.handle.net/1884/26630.
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Resumo: Introdução: Os tumores estromais gastrointestinais (GIST) são neoplasias raras que se originam das células intersticiais de Cajal .A última década foi de grande avanço com o esclarecimento dos mecanismos moleculares, seguido da terapia molecular, que propiciaram um grande aumento na sobrevida. Objetivo: Avaliar a experiência do Hospital de Clínicas de Curitiba no tratamento do GIST localizado e avançado, com análise das características clínicas e anatomo-patológicas e uso do imatinibe. Metodologia: Estudo retrospectivo de 32 pacientes com diagnóstico de GIST por imunohistoquímica, c-Kit positivo, no período de 2003 a 2008 Resultados: Os dados evidenciaram que a idade mediana foi de 66 anos, o tamanho mediano de 8,4 cm e as localizações mais frequentes foram estômago em 46,9% e intestino delgado em 40,9%. Considerado com alto risco de agressividade 37,5% dos pacientes. Do grupo total, 23 pacientes apresentavam doença localizada no diagnóstico, sendo que 39,1% recaíram, e 9 pacientes doença avançada. O seguimento mediano foi de 43,7 meses. A sobrevida global em 5 anos no grupo total foi de 56,2%, sendo que na doença localizada foi de 73,8% e na doença avançada foi de 37,5% (p=0,03). Não foi observado impacto dos fatores prognósticos na sobrevida. A utilização do imatinibe ocorreu em 16 pacientes, 43,8% por metástase inicial, 37,5% por recaída a distância, 12,5% por recaída local e 6,2% por margem cirúrgica comprometida. A sobrevida global com uso do imatinibe mediana foi de 53 meses e a sobrevida livre de primeira progressão de 32,9 meses. Ocorreu uma boa tolerabilidade ao imatinibe, com 2 pacientes com toxicidade grau 3 e apenas dois pacientes utilizaram o sunitinibe. Conclusão: A maioria dos tumores foram grandes, de localização gástrica e de alto risco de agressividade. A taxa de recaída na doença localizada foi alta. E a sobrevida global dos pacientes de doença localizada e que utilizaram o imatinibe foi considerada satisfatória.
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Devine, Raymond David. „Tumor Induced Cardiovascular Dysfunction“. The Ohio State University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=osu1448969937.
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Ylikorkala, Antti. „The LKB1 tumor suppressor“. Helsinki : University of Helsinki, 2001. http://ethesis.helsinki.fi/julkaisut/laa/haart/vk/ylikorkala/.
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Salmenkivi, Kaisa. „Tumor markers in pheochromocytomas“. Helsinki : University of Helsinki, 2003. http://ethesis.helsinki.fi/julkaisut/laa/haart/vk/salmenkivi/.
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Costa, Alexandra Fontes da. „Análise imunoistoquímica das proteínas maspin, p63 e bcl2 em tumor odontogênico queratocístico, cisto dentígero e ameloblastoma“. Universidade de São Paulo, 2007. http://www.teses.usp.br/teses/disponiveis/23/23141/tde-13082007-162555/.
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Os cistos e tumores odontogênicos sempre tiveram grande importância dentro da Odontologia, seja pela grande prevalência clínica seja pelo grande acometimento do indivíduo afetado pela lesão. A nova classificação da Organização Mundial de Saúde trouxe a mudança de categoria do queratocisto, que recebe agora a nômina de tumor odontogênico queratocístico, e que figura não mais na categoria de cisto odontogênico de desenvolvimento, mas sim de tumor odontogênico. Certa precipitação nessa mudança levou alguns autores a sugerirem a necessidade de estudos que esclareçam as características clínicas e histopatológicas dessa lesão para que se tenha uma classificação realmente precisa. O grande paradigma dessa lesão é: ao mesmo tempo em que apresenta características histológicas de um cisto, possui um comportamento clínico agressivo mais comumente observado nos tumores. O que realmente difere esta lesão das outras lesões que se inseriam no mesmo grupo é o padrão de crescimento diferenciado do tumor odontogênico queratocístico em relação às outras lesões císticas. Sendo assim, poderia se suspeitar que essa lesão possua um potencial proliferativo maior do que as outras que anteriormente pertenciam ao mesmo grupo, denotando uma regulação diferenciada do mecanismo proliferação-apoptose. Este estudo teve como objetivo comparar o tumor odontogênico queratocístico com uma lesão cística - o cisto dentígero - e com uma lesão tumoral - o ameloblastoma ? por meio de marcadores imunoistoquímicos para supressão tumoral e anti-apoptose. Os resultados demostraram que a maior diferença entre essas lesões está principalmente na atividade apoptótica, já que somente o resultado de bcl2 foi estatisticamente significante entre essas lesões.Odontogenic cysts and tumors have always had a great importance in Dentistry, for its high clinical prevail and for its noticeable invasive behavior. The new classification released by WHO rearranged keratocyst, that is named now odontogenic keratocystic tumor, classifying it no longer as a development cyst, but now as odontogenic tumor. Certain haste in this change brought some authors to suggest the necessity of more studies to clarify the feautures of such lesions to determine a more accurate classification. The greatest paradigm of this lesion is that it shows cyst-like histological characteristics and simultaneuosly it has an aggressive clinical behavior, which is more commonly observed in tumors. The main difference between this lesion and the others cystic lesions is the growth pattern, which suggests that the odontogenic keratocystic tumor has higher proliferative potential than other cystic lesions. The aim of this research was to compare odontogenic keratocystic tumor with a cystic lesion ? dentigerous cyst ? and with a tumoral lesion ? ameloblastoma ? using tumor suppressor and anti-apoptosis immunohistochemical expression. Results show that the more important difference among the analysed lesions is apoptosis activity, since only bcl2 staining was significantly different among them.
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Bassani, Nicklas. „New targets in tumor angiogenesis to block tumor re-growth and therapeutic resistance“. Doctoral thesis, Universitat de Barcelona, 2017. http://hdl.handle.net/10803/462953.
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Antiangiogenic drugs are used clinically for treatment of different types of cancers and in the case of renal cell carcinoma (RCC) are now standard first-line treatments (Rini, 2009). Nevertheless, these agents mainly serve to stabilize the disease but are not able to eliminate all tumor cells and resistance eventually develops concomitant with progression (Kerber and Folkman, 2002).
Using different orthoxenograft mouse models of RCC we confirmed that inhibitors of the VEGF pathway have a therapeutic window of effectiveness but unfortunately adaptation and tumor relapse always occur.
Several different mechanisms of resistance to antiangiogenics have been already described, many concerning the activation of compensatory signals that produce re-vascularization and tumor re-growth. (Bergers and Hanahan, 2008). In our study we determined that even if resistance is characterized by the up-regulation of the pro-angiogenic enzyme ECGF1 (previous data from the lab); re-vascularization does not occur, the vascular trimming is maintained by the treatment pointing to an alternative mode of adaptation.
Using two different approaches, we demonstrated that PD-ECGF1 is responsible of the acquisition of resistance to anti-anigiogenics. In fact, its enzymatic inhibition as second-line treatment post resistance resulted in the arrest and stabilization of tumor growth. PD-ECGF1 inhibition did not increase the anti-vascular effect of DC101, confirming that resistance was vessel independent, but dramatically affected tumor cell proliferation and apoptosis. Considering the numerous proprieties ascribed to its final metabolite 2-deoxy-D-ribose (Ikeda et al., 2006; Bjinsdorp et al., 2008), we evaluated its role, finding that recombinant 2-deoxy-D-ribose nullified the effect of AEAC on 786O- and Ren28 tumor growth rescuing tumor cell proliferation and apoptosis, without promoting re-vascularization. Overall these findings, confirmed also in an in vitro setting, demonstrate that tumor stroma plays a minor role in this model of anti-angiogenics resistance, and that PD-ECGF1 acts mainly intracellularly supporting tumor cell proliferation and protecting from apoptosis by its enzymatic activity and final metabolite 2-deoxy-D-ribose.
Using a genetic approach in which PD-ECGF1 protein expression was silence as a second line of treatment post DC101-resistance, mimicking what done pharmacologically, we confirmed and improved the anti-tumoral response described, without perceiving any doxycycline toxic effect. In fact, PD-ECGF1 genetic knock down resulted in a complete arrest of tumor progression enhancing the merely partial stabilization produce by AEAC treatment in 786O- tumor bearing mice.
Unfortunately VEGFR-blockers can’t be used in vitro on cancer cells, and to verify this hypothesis we decided to mimic the final effects of anti-angiogenic treatments, finding that under nutrient deprivation conditions cancer cells significantly up-regulate PD-ECGF1 expression, and metabolizing thymidine acquired considerable growth advantages.
Finally, the analysis of plasma and tissue samples of ccRCC patients from the Bellvitge Hospital confirm in a clinical set that PD-ECGF1 is exclusively found in pathologic conditions, where if highly expressed correlates with poor prognosis, suggesting that might represent a good therapeutic predictor factor. Moreover, the analysis of tissues biopsies before and after anti-angiogenic treatment revealed that whilst PD-ECGF1 treatment-induce up-regulation was a common feature, the patients that unfortunately didn’t respond showed the sharp difference, confirming PD-ECGF1 as a possible therapeutic target.Los fármacos antiangiogénicos se usan clínicamente para el tratamiento de diferentes tipos de cáncer y en el caso del carcinoma de células renales (CCR) representan la primera diana terapéutica (Rini, 2009). Sin embargo, no son capaces de eliminar todas las células tumorales y muchos pacientes desarrollan resistencia al tratamiento y recrecimiento tumoral (Kerber y Folkman, 2002). Mediante el uso de diferentes modelos de ratón hemos confirmado que los inhibidores de la vía VEGF tienen una limitada ventana terapéutica de efectividad, seguida desafortunadamente de adaptación y recaída tumoral que en nuestro estudio esta` caracterizada por la regulación positiva de la enzima PD-ECGF1. Usando dos enfoques diferentes, demostramos que PD-ECGF1 es responsable de la adquisición de resistencia a anti-anigiogénicos. De hecho, su inhibición enzimática como tratamiento de segunda línea después de la resistencia dio como resultado la detención y la estabilización del crecimiento tumoral. La inhibición de PD-ECGF1 no aumentó el efecto antivascular de DC101, pero afectó de manera dramática la proliferación y apoptosis de las células tumorales. Teniendo en cuenta las numerosas propiedades atribuidas a su metabolito final 2-deoxy-D-ribose (Ikeda et al., 2006; Bjinsdorp et al., 2008), evaluamos su papel, encontrando que la 2-deoxy-D-ribose anuló el efecto de la inhibición de PD-ECGF1 rescatando el crecimiento tumoral. Experimentos en vitro demostraron como las células tumorales incrementaban la expresión de PD-ECGF1 en condiciones de falta de nutrientes haciéndonos especular que esta proteína tenga un papel en la adaptación metabolica. Finalmente, el análisis de muestras de plasma y tejido de pacientes con ccRCC del Hospital de Bellvitge confirma en un conjunto clínico que PD-ECGF1 se encuentra exclusivamente en condiciones patológicas, donde se correlaciona con mal pronóstico, sugiriendo que podría representar un buen factor predictor terapéutico.
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Lammerts, Ellen. „Tumor stroma in anaplastic thyroid carcinoma interstitial collagen and tumor interstitial fluid pressure /“. Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2001. http://publications.uu.se/theses/91-554-5198-5/.
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To, Kit-yan, und 杜潔欣. „Beta-catenin signaling in the interactions of tumor cells and the tumor microenvironment“. Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2015. http://hdl.handle.net/10722/211113.
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Payne, Kyle K. „Immunotherapy of Cancer: Reprogramming Tumor/Immune Cellular Crosstalk to Improve Anti-Tumor Efficacy“. VCU Scholars Compass, 2015. http://scholarscompass.vcu.edu/etd/3939.
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Immunotherapy of cancer has been shown to be promising in prolonging patient survival. However, complete elimination of cancer and life-long relapse-free survival remain to be major challenge for anti-cancer therapeutics. We have previously reported that ex vivo reprogramming of tumor-sensitized immune cells by bryostatin 1/ionomycin (B/I) and the gamma-chain (γ-c) cytokines IL-2, IL-7, and IL-15 resulted in the generation of memory T cells as well as CD25+ NKT cells and CD25+ NK cells. Adoptive cellular therapy (ACT) utilizing these reprogrammed immune cells protected FVBN202 mice from tumor challenge, and overcame the suppressive functions of myeloid-derived suppressor cells (MDSCs). We then demonstrated that the presence of CD25+ NKT cells was required for anti-tumor efficacy of T cells as well as their resistance to MDSCs. Similar results were obtained by reprogramming of peripheral blood mononuclear cells (PBMC) from patients with early stage breast cancer, demonstrating that an increased frequency of CD25+ NKT cells in reprogrammed immune cells was associated with modulation of MDSCs to CD11b-HLA-DR+ immune stimulatory cells. Here, we tested the efficacy of immunotherapy in a therapeutic setting against established primary breast cancer (Chapter One), experimental metastatic breast cancer (Chapter Three) as well as against minimal residual disease (MRD) in patients with multiple myeloma (Chapter Two). We evaluated the ability of reprogrammed immune cells, including CD25+ NKT cells, to convert MDSCs to myeloid immune stimulatory cells, in vivo; this resulted in the identification and characterization of a novel antigen presenting cell (APC). These novel immune stimulatory cells differed from conventional APCs, including dendritic cells (DCs) and macrophages. We have also demonstrated that enhancing immunogenicity of mammary tumors by treatment with Decitabine (Dec) along with overcoming MDSCs by utilizing reprogrammed T cells and NKT cells in ACT prolongs survival of animals, but fails to eliminate the tumor. However, targeting cancer during a setting of MDR, when tumor cells are dormant, results in objective responses as evidenced in our multiple myeloma studies. This suggests that targeting breast cancer with immunotherapy following conventional therapies, in a setting of residual disease when tumor cells are dormant, may be effective in eliminating such residual cells or maintaining dormancy and extending time-to-relapse for breast cancer patients.
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Pearce, Janina V. „The Role of Tumor and Tumor Microenvironment on Breast Cancer-Associated Adipocyte Plasticity“. VCU Scholars Compass, 2019. https://scholarscompass.vcu.edu/etd/5933.
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Cancer-associated cachexia is a condition defined by a sustained net-negative energy imbalance. Although the different types of adipose tissue – white, beige, and brown – have been implicated in contributing to cancer-associated cachexia, the mechanisms of these maladaptive changes and their impact on whole-body energy expenditure have not been fully elucidated. Using breast cancer as our model, we demonstrate white adipose tissue browning in murine and human breast cancer; furthermore, we demonstrate that this effect is extremely localized and takes place early in tumor progression. We utilized in vitro cell culture techniques and demonstrate that cancer secreted factors and cross-talk with white adipocytes decrease expression of classic white adipose tissue-related genes. We also demonstrate in murine and human culture models that cancer secreted factors reduce white adipocyte lipid droplet size, and cross-talk between cancer cells and adipocytes results in an increase in lipolysis-related gene expression. Interestingly, our results strongly suggest that in mice, neither cancer secreted factors nor cross talk with adipocytes can induce white adipose tissue browning, indicate that this process likely occurs independently of direct cancer interactions with local white adipocytes. We demonstrate that interleukin 6, a cytokine with previous implications in white adipose tissue browning, induces interleukin 6-mediated signaling; however, that signaling alone is not enough to directly induce white adipose tissue browning. We present preliminary data suggesting that immune cell population shifts within the white adipose tissue of mice with breast cancer tumors may be source of white adipose tissue browning. We show that the Virginia Commonwealth University Health System has an identifiable population of patients with cancer with what we hypothesize as maladaptive thermogenic adipose tissue activity, and discuss ongoing experiments aimed at understanding the implications of these changes on whole body energy expenditure in human patients. Lastly, in a case of autoimmune diabetes mellitus in the setting of an extra-adrenal paraganglioma, we demonstrate that the interaction between cancer and whole-body metabolism is multifaceted. Together, these experiments demonstrate that adipose tissue plasticity occurs in breast cancer (and other cancers), and that different drivers for individual changes exist within the tumor microenvironment. We predict that further exploration of the exact mechanisms and translational implications will provide useful information to lead to new therapeutic treatments for patients with cancer-associated cachexia.
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D'ORIA, CLAUDIA. „ORGANOID MODELS TO STUDY THE CROSSTALK BETWEEN TUMOR CELLS AND TUMOR INFILITRATING LYMPHOCYTES“. Doctoral thesis, Università degli Studi di Milano, 2020. http://hdl.handle.net/2434/700588.
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Recent advances in 3D culture technology allow embryonic and adult mammalian stem cells to generate organoids in vitro, which reflect key structural and functional properties of organs they originate (Clevers H., Cell, 2016). For this reason, they represent a powerful tool to study human physiological and pathological processes, in particular to investigate complex processes like tumorigenesis and tumor growth, resembling the in vivo mechanisms. In particular, in tumor contest neoplastic cells activate several strategies to escape from immunesurveillance, such as the recruitment of immune cells with immunosuppressive functions. In this regard, CD4+ T regulatory cells (Tregs), physiologically engaged in the maintenance of immunological self-tolerance and immune homeostasis, are potent suppressors of effector cells and found at high frequencies in various types of cancer. A recent transcriptome analysis performed in our lab (De Simone M. et al., Immunity, 2016) revealed that tumor-infiltrating Tregs, isolated from CRC (colorectal cancer) and NSCLC (non-small cell lung cancer) patients, expressed a unique and specific gene signature, correlated with patients’ survival. In line with our findings, non-lymphoid tissue infiltrating Tregs can exhibit specific phenotypes and transcriptional profile involved in glucose metabolism, tissue repair and muscle regeneration, far from their well-established suppressive roles (Cipolletta D. et al., 2012; Arpaia N. et al., 2015). Thus, our work wants to evaluate the immune dependent and independent function of tissue- infiltrating Tregs, exploiting a co-culture model with normal and colon cancer- derived organoids. This approach could be suitable to recapitulate primary tumorigenesis, cancer microenvironment effect on Tregs recruitment and phenotype and, vice versa, infiltrating Tregs influence on tumor onset, growth and tissue homeostasis. In order to answer our biological questions by using organoid model, we first of all derived organoids starting from CRC patients’ biopsies, according to protocol published by Sato T. et al. (2011). We generated a biobank of 20 and 28 human- normal and tumoral colon- derived organoid lines, respectively, from tumoral biopsies and the adjacent normal mucosa of patients affected by colorectal cancer. In particular, these organoid lines can be propagated, frozen and defrosted like any tumour cell line, morphologically recapitulating the cellular composition and architecture of colon primary tissue and, importantly, representative of all CRC molecular subtypes. Moreover, our RNA-seq bulk analysis on our organoid lines unveiled that they are very stable from the transcriptional point of view during passages and preserve the inter-individual heterogeneity. Furthermore, our ChIP-seq data showed that our library resembled the same epigenetic landscape of colorectal primary tumour; in this context our study represents an innovative approach to investigate epigenetic processes leading CRC development and progression. Considering that Tumor-infiltrating- Tregs (TI- Tregs) were found to express a peculiar gene signature (De Simone et al., 2016; Plitas et al., 2016), we decided to exploit organoid model to better elucidate processes leading the development and the recruitment of these cells at the tumour site. To this end, we proceeded with the establishment of Tregs- PDO co-culture, assessing the feasibility of this system and evaluating Tregs viability in organoid culture conditions, without observing any significant differences in their survival. Moreover, we evaluated their ability to migrate into 3D organoid structure, revealing their capacity to overcome firstly the obstacle represented by Matrigel (which mimics extracellular matrix) and then creeping into the 3D architecture of organoids, recapitulating the same behaviour they have when recruited at the tumour site. An important evidence about the possible influence of tumoroids on Treg phenotype came from our preliminary co-culture experiment, revealing that PDO-Tregs co-culture upregulated the expression of PDL1 (one of the genes belonging to TI-Treg signature (De Simone et al., 2016)) specifically on Treg but not on Tconv cells. On the other hand, with our co-culture preliminary experiment we observed that expanded TI-Tregs enhanced PDL1 expression on tumoroid cells, which not happened when organoids were co-cultivated with Tconv cells, suggesting the possible influence of Tregs on the expression of specific molecules on cancer cell surface. In conclusion, the exploitation of TI-Treg-PDO co-culture could shed light on the interplay between tumor and TI-Tregs, giving the opportunity to potentially interfere in this crosstalk and design a peculiar anticancer therapy targeting TI-Tregs in a personalized manner.
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Carter, Ashley. „AN EXAMINATION OF OBESITY IN PEDIATRIC BRAIN TUMOR SURVIVORS: FOOD FOR THOUGHT“. Thesis, The University of Arizona, 2015. http://hdl.handle.net/10150/528118.
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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.Background: Great strides have been made in childhood cancer treatment efficacy over the past two decades leading to improved survival rates, and now attention is being directed toward identifying and understanding complications that affect many of these patients as they reach adulthood. Obesity is a well‐recognized late effect that has many potential long‐term consequences some of which include cardiovascular disease, type II diabetes mellitus, dyslipidemia and even death. Materials/Methods: We conducted a retrospective chart review to determine the prevalence of obesity among survivors of pediatric brain tumors 5 years after the completion of therapy and compare this to the general pediatric population of the same age. We also sought to identify potential risk factors for the development of obesity among survivors of childhood brain tumors. Obesity was defined as a body mass index (BMI) greater than the 95th percentile for age and gender as defined by the most recent Center for Disease Control growth curves. Results: We identified 96 patients who met our inclusion criteria, however only 43 had follow‐up data at 5 years after the completion of therapy to be included in final analysis. Of 43 patients, 5 (11.63%) were obese 5 years after completion of therapy. The CDC sites general population obesity rates in three age groups: 2‐5 years (8.4% obesity rate), 6‐ 11 years (18% obesity rate), 12‐19 years (21% obesity rate). Using CDC guidelines, we found no significant difference between the obesity rate among the brain tumor survivor population for each age group and the general population, p‐values of 0.865, 0.865, and 0.249 respectively. Conclusion: Our small sample size was likely not adequate to find a significant difference between the two groups or identify risk factors associated with the development of obesity. Larger studies are needed to further examine the risk of obesity among pediatric brain tumor survivors and to identify risk factors associated with this late effect.
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Kasnitz, Nadine [Verfasser], und Manfred [Akademischer Betreuer] Rohde. „Tumor-associated neutrophils during Pseudomonas aeruginosa-mediated tumor therapy / Nadine Kasnitz ; Betreuer: Manfred Rohde“. Braunschweig : Technische Universität Braunschweig, 2016. http://d-nb.info/1175819042/34.
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Szot, Christopher Sang. „A three-dimensional in vitro tumor model representative of the in vivo tumor microenvironment“. Diss., Virginia Tech, 2013. http://hdl.handle.net/10919/49597.
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The inability to accurately reproduce the complexities of the in vivo tumor microenvironment with reductionist-based two-dimensional in vitro cell culture models has been a notable deterrent in identifying therapeutic agents that reliably translate to in vivo animal and human clinical trials. In an effort to address this, a growing number of three-dimensional (3D) in vitro tumor models capable of mimicking specific tumorigenic processes have emerged within the last decade. This concept stems from the understanding that cells cultured within 3D in vitro matrices have the ability to acquire phenotypes representative of the in vivo microenvironment. The objective of this project was to apply a tissue engineering approach towards developing a 3D in vitro tumor angiogenesis model. Initially, different scaffolds were investigated for supporting 3D tumor growth, including bacterial cellulose, electrospun polycaprolactone/collagen I, and highly porous electrospun poly(L-lactic acid). However, cancer cells cultured on these scaffolds demonstrated poor adhesion, sufficient adhesion with poor infiltration, and increased but still inadequate infiltration, respectively. Collagen I hydrogels were chosen as an appropriate scaffold for facilitating 3D in vitro tumor growth for two reasons -- cell-mediated degradation and immediate 3D cell growth. It was hypothesized that cancer cells cultured within collagen I hydrogels could be encouraged to recapitulate key characteristics of in vivo tumor progression. MDA-MB-231 human breast cancer cells were shown to experience hypoxia and undergo necrosis in response to limitations in oxygen diffusion and competition for nutrients. Upregulation of hypoxia-inducible factor-1" resulted in a significant increase in vascular endothelial growth factor gene expression. To capitalize on this endogenous angiogenic potential, microvascular endothelial cells were cultured on the surface of the designated "bioengineered tumors." It was hypothesized that paracrine signaling between tumor and endothelial cells co-cultured within this system would be sufficient for inducing an angiogenic response in the absence of exogenous pro-angiogenic growth factors. Endothelial cells in the co-culture group were shown to invasively sprout into the underlying collagen matrix, forming a capillary-like tubule network. This project culminated with the establishment of an improved in vitro tumor model that can be used as a tool for accurate evaluation and refinement of cancer therapies.Ph. D.
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Senkowski, Wojciech. „High-throughput screening using multicellular tumor spheroids to reveal and exploit tumor-specific vulnerabilities“. Doctoral thesis, Uppsala universitet, Cancerfarmakologi och beräkningsmedicin, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-320598.
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High-throughput drug screening (HTS) in live cells is often a vital part of the preclinical anticancer drug discovery process. So far, two-dimensional (2D) monolayer cell cultures have been the most prevalent model in HTS endeavors. However, 2D cell cultures often fail to recapitulate the complex microenvironments of in vivo tumors. Monolayer cultures are highly proliferative and generally do not contain quiescent cells, thought to be one of the main reasons for the anticancer therapy failure in clinic. Thus, there is a need for in vitro cellular models that would increase predictive value of preclinical research results. The utilization of more complex three-dimensional (3D) cell cultures, such as multicellular tumor spheroids (MCTS), which contain both proliferating and quiescent cells, has therefore been proposed. However, difficult handling and high costs still pose significant hurdles for application of MCTS for HTS. In this work, we aimed to develop novel assays to apply MCTS for HTS and drug evaluation. We also set out to identify cellular processes that could be targeted to selectively eradicate quiescent cancer cells. In Paper I, we developed a novel MCTS-based HTS assay and found that nutrient-deprived and hypoxic cancer cells are selectively vulnerable to treatment with inhibitors of mitochondrial oxidative phosphorylation (OXPHOS). We also identified nitazoxanide, an FDA-approved anthelmintic agent, to act as an OXPHOS inhibitor and to potentiate the effects of standard chemotherapy in vivo. Subsequently, in Paper II we applied the high-throughput gene-expression profiling method for MCTS-based drug screening. This led to discovery that quiescent cells up-regulate the mevalonate pathway upon OXPHOS inhibition and that the combination of OXPHOS inhibitors and mevalonate pathway inhibitors (statins) results in synergistic toxicity in this cell population. In Paper III, we developed a novel spheroid-based drug combination-screening platform and identified a set of molecules that synergize with nitazoxanide to eradicate quiescent cancer cells. Finally, in Paper IV, we applied our MCTS-based methods to evaluate the effects of phosphodiesterase (PDE) inhibitors in PDE3A-expressing cell lines. In summary, this work illustrates how MCTS-based HTS yields potential to reveal and exploit previously unrecognized tumor-specific vulnerabilities. It also underscores the importance of cell culture conditions in preclinical drug discovery endeavors.
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Zhang, Xiaomeng. „MRI OF TUMOR pH AND PERFUSION“. Diss., The University of Arizona, 2010. http://hdl.handle.net/10150/195293.
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In the early 1920s, Otto Warburg demonstrated that tumor cells have a capacity to convert glucose and other substrates into lactic acid instead of CO2 and water, even under aerobic conditions. Consequently, Warburg assumed that the intracellular pH (pHi) of tumor was acidic. However, later studies have shown that maintenance of pHi within a pH range of 7.0-7.2 is necessary for normal cellular proliferation and that the extracellular pH (pHe) is partially acidic in solid tumors. A low pHe may be an important factor inducing invasive behavior in tumor cells. Research into causes and consequences of this acid pH of tumors are highly dependent on accurate, precise and reproducible measurements. Techniques for measuring tissue pHi and pHe have undergone great changes since 1950s. From microelectrode and dye distribution studies, measurement of pH underwent a revolution with the advent of pH-sensitive dyes that could be loaded into the cytosol. Further significant advances have come from the measurement of cell and tissue pH in whole organisms by magnetic resonance spectroscopy (MRS), magnetic resonance imaging (MRI) and pH-sensitive Positron Emission Tomography (PET) radiotracers.
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Vitaliti, Alessandra. „Inhibition of tumor induced angiogenesis /“. [S.l.] : [s.n.], 1999. http://e-collection.ethbib.ethz.ch/show?type=diss&nr=13409.
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Barendsz-Janson, A. F. „Predictive models of tumor angiogenesis“. [Maastricht : Maastricht : Universiteit Maastricht] ; University Library, Maastricht University [Host], 1998. http://arno.unimaas.nl/show.cgi?fid=8524.
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Hellebrekers, Debby Maria Elisabeth Ida. „Epigenetic regulation of tumor angiogenesis“. Maastricht : Maastricht : Universiteit Maastricht ; University Library, Universiteit Maastricht [host], 2006. http://arno.unimaas.nl/show.cgi?fid=5612.
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Sheikholvaezin, Ali. „Recombinant antibodies and tumor targeting“. Doctoral thesis, Umeå : Univ, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-875.
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Fujioka, Kaoru. „Centrosome aberrations and tumor development /“. Stockholm, 2003. http://diss.kib.ki.se/2003/91-7349-627-8/.
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Weens, William. „Mathematical modeling of liver tumor“. Phd thesis, Université Pierre et Marie Curie - Paris VI, 2012. http://tel.archives-ouvertes.fr/tel-00779177.
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Comme démontre récemment pour la régénération du foie après un dommage cause par intoxication, l'organisation et les processus de croissance peuvent être systématiquement analyses par un protocole d'expériences, d'analyse d'images et de modélisation [43]. Les auteurs de [43] ont quantitativement caractérise l'architecture des lobules du foie, l'unité fonctionnelle fondamentale qui constitue le foie, et en ont conçu un modèle mathématique capable de prévoir un mécanisme jusqu'alors inconnu de division ordonnée des cellules. La prédiction du modèle fut ensuite validée expérimentalement. Dans ce travail, nous étendons ce modèle a l'échelle de plusieurs lobules sur la base de résultats expérimentaux sur la carcinogène dans le foie [15]. Nous explorons les scénarios possibles pouvant expliquer les différents phénotypes de tumeurs observés dans la souris. Notre modèle représente les hépatocytes, principal type de cellule dans le foie, comme des unités individuels avec un modèle a base d'agents centré sur les cellules et le système vasculaire est représenté comme un réseau d'objets extensibles. L'équation de Langevin qui modélise le mouvement des objets est calculée par une discrétisation explicite. Les interactions mécaniques entre cellules sont modélisées avec la force de Hertz ou de JKR. Le modèle est paramètre avec des valeurs mesurables a l'échelle de la cellule ou du tissue et ses résultats sont directement comparés avec les résultats expérimentaux. Dans une première étape fondamentale, nous étudions si les voies de transduction du signal de Wnt et Ras peuvent expliquer les observations de [15] où une prolifération instantanée dans les souris mutées est observée seulement si 70% des hépatocytes sont dépourvues d'APC. Dans une deuxième étape, nous présentons une analyse de sensibilité du modèle sur la rigidité de la vasculature et nous la mettons en relation avec un phénotype de tumeur (observe expérimentalement) où les cellules tumorales sont bien différentiées. Nous intégrons ensuite dans une troisième 'étape la destruction de la vasculature par les cellules tumorales et nous la mettons en relation avec un autre phénotype observe expérimentalement caractérise par l'absence de vaisseaux sanguins. Enfin, dans la dernière étape de notre étude nous montrons que des effets qui sont détectables dans les petits nodules tumoraux et qui reflètent les propriétés des cellules tumorales, ne sont plus présents dans la forme ou dans le phénotype des tumeurs d'une taille excédant la moitié de celle d'un lobule.
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Mercier, Laurence. „Ultrasound-guided brain tumor resection“. Thesis, McGill University, 2012. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=107629.
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Malignant gliomas are the most common type of primary brain tumors in adults. Contrarily to brain metastases that have clear borders, malignant gliomas are poorly circumscribed lesions because they diffusely infiltrate the brain parenchyma. When possible, standard treatment of gliomas includes surgical resection, though surgeons unintentionally leave behind some of the tumor more than 50% of the time. Two factors are mainly responsible for this situation. First, most current neuronavigation systems are based on preoperative images; these systems become less accurate as the surgery progresses and the brain goes through important changes and deformations. Second, glioma boundaries are often visually and haptically difficult to determine. This is an unfortunate situation since maximum safe resection of these tumors correlates with longer survival times in patients presenting either a low-grade or high-grade glioma. By providing real-time images, intraoperative imaging techniques aid neurosurgeons achieve more complete resections while also helping to prevent damage to normal brain. In this thesis, I have investigated the use of intraoperative ultrasound to guide glioma surgery. To achieve this, I have used the prototype neuronavigation system developed by our research group: the IBIS NeuroNav system.The aim of the first paper was to evaluate the precision and accuracy of IBIS NeuroNav. Four aspects of the system were characterized: 1) the ultrasound probe calibration, 2) the temporal calibration, 3) the patient-to-image registration and 4) the mean intial MRI-ultrasound misalignment. IBIS NeuroNav was found to have an accuracy similar to other comparable systems in the literature.The goal of the second paper was to present a new technique for the rigid registration of the preoperative MRI to the pre-resection intraoperative ultrasound. Initially these images generally have a slight misalignment. However, surgeons find ultrasound images easier to interpret when they are properly aligned with MRI. The results of our investigation showed that the proposed registration technique robustly improved the MRI–ultrasound alignment when compared with the initial alignment.The objective of the third paper was to test rigid and non-rigid registration techniques to better align the pre- and post-resection ultrasound images to facilitate interpretation of the latter. A simple correlation coefficient based nonlinear registration proved to significantly improve the alignment between the pre- and post-resection ultrasound images. One of the biggest challenges of many technical scientists in the field of medical imaging is to find clinical images on which to validate new image processing algorithms. To address this issue, the fourth paper presents an online database in which we share our acquired preoperative MRI and intraoperative ultrasound images with the medical imaging community. We hope that this work will make it easier for neurosurgeons to use intraoperative ultrasound to guide glioma surgery and will eventually lead to improved surgical accuracy and prolonged patient survival.Les gliomes malins sont les tumeurs primaires les plus répandues chez l'adulte. Contrairement aux métastases cérébrales qui ont des contours bien définis, les gliomes malins infiltre le cerveau environnant et ont souvent des contours plus indistincts. En présence d'un gliome, en général la résection chirurgicale est l'approche privilégiée. Par ailleurs, dans un cas sur deux les neurochirurgiens laissent involontairement une partie de la tumeur. Deux facteurs principaux sont responsables de cet état de fait. Premièrement, la plupart des systèmes de neuronavigation actuels sont basés sur des images préopératoires. Parce que le cerveau subit d'importants changements lors de la chirurgie, ces images perdent en précision au fil de l'opération. En second lieu, les limites d'un gliome sont souvent difficiles à déterminer de façon précise, à la fois avec le sens de la vue et du toucher. Cette situation est regrettable puisqu'une résection à la fois maximale et sécuritaire de ces tumeurs est corrélée avec une survie prolongée des patients présentant un gliome de bas ou de haut grade. L'imagerie peropératoire permet d'obtenir des images en temps réel, aidant ainsi le chirurgien à faire une résection plus complète, tout en protégeant les tissus sains. Dans cette thèse j'ai étudié l'usage de l'ultrason peropératoire afin de guider la résection d'un gliome. À cette fin, j'ai utilisé le prototype de système de neuronavigation développé dans notre groupe de recherche : le système IBIS NeuroNav. Le but du premier article était d'évaluer la précision d'IBIS NeuroNav. Quatre composants du système ont été considérés : 1) le calibrage de la sonde ultrason 2) le calibrage temporel 3) le recalage patient-image et 4) le recalage IRM-ultrason. Nous avons constaté qu'IBIS NeuroNav avait une précision similaire aux autres systèmes comparables présentés dans la littérature. Le but du deuxième article était de présenter une nouvelle technique de recalage rigide entre l'IRM préopératoire et l'ultrason pré-résection intraopératoire. Au départ, ces images sont généralement légèrement désalignées. Or, les chirurgiens trouvent l'interprétation des images ultrasons plus facile lorsqu'elles sont correctement alignées avec l'IRM. Nos résultats montrent que la nouvelle technique proposée améliore de façon significative l'alignement IRM-ultrason.Le but du troisième article était de tester des méthodes de recalage rigide et non-rigide pour améliorer l'alignement des images ultrasons pré- et post-opératoires, afin de faciliter l'interprétation des seconds. Nous avons trouvé qu'une méthode de recalage utilisant un simple coefficient de corrélation améliorait significativement cet alignement. Un des nombreux défis des scientifiques techniques du domaine de l'imagerie médicale est de trouver des images cliniques sur lesquelles valider leurs nouveaux algorithmes. L'objectif du quatrième papier était précisément de pallier à cette difficulté en partageant avec la communauté scientifique les images acquises pour les papiers précédents. Nous sommes confiants que les résultats présentés dans cette thèse faciliteront l'utilisation par les neurochirurgiens des ultrasons peropératoires. Une survie prolongée de trop nombreux patients en dépend!
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Weiß, Jakob. „Regulation Tumor-infiltrierender dendritischer Zellen“. Diss., Ludwig-Maximilians-Universität München, 2014. http://nbn-resolving.de/urn:nbn:de:bvb:19-178105.
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Chowdury, Simon. „Retroviral targeting to tumor antigens :“. Thesis, University College London (University of London), 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.411165.
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Mathis, Robert Austin. „Intra-tumor heterogeneity and evolution“. Thesis, Massachusetts Institute of Technology, 2017. http://hdl.handle.net/1721.1/113432.
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Thesis: Ph. D., Massachusetts Institute of Technology, Department of Biology, 2017.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.
Although the treatment of cancer is a major focus of biomedical research, many cancers are extremely hard to treat. Tumors likely resist treatment because each tumor is heterogeneous, and can evolve. Although tumor evolution has long been appreciated, it remains incompletely understood. In this thesis, I will explore two questions related to cancer heterogeneity and evolution: how evolution can affect plastic phenotypes, and the role of purifying selection in cancer evolution. Different cell states or phenotypes have been observed within tumors, and they are associated with treatment resistance and metastasis. The observation that these phenotypes are plastic leads to a conundrum: how can selection act on such an unstable phenotype? We determined that plasticity, in the form of cell state bias, varies widely across clones in a tumor. These different biases are heritable, with each cell faithfully passing its differentiation bias to its daughters. Simulations revealed that this makes plasticity an evolvable phenotype--- in a changing environment, an optimal state bias will be selected. The second question explored in this thesis is the role of purifying selection in cancer evolution. It is widely thought that tumor evolution is dominated by positive selection. We posited that, as in the evolution of species, purifying selection would prevent the fixation of deleterious mutations in tumors. Through computational analysis of tumor genomes, we determined that purifying selection acts to remove deleterious mutations. Genes under purifying selection must be important to tumors in vivo, as only mutations in these genes would be problematic. Consistent with this prediction, most genes under purifying selection in tumors were essential in cancer cell lines. To find genes essential to tumors but not generally cell-essential, we developed a method to find genes under increased purifying selection in one tumor type over others. This revealed a number of pathways under selection in melanomas, but not other tumor types, such as DNA damage pathways. By seeking genes important to tumors, but not generally essential, our analysis revealed potential therapeutic targets. Purifying selection offers an unprecedented view into which genes are essential to tumors in vivo, a finding predominantly inaccessible through experimentation.
by Robert Austin Mathis.
Ph. D.
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Graff, Christilyn Paula. „Antibody engineering for tumor immunotherapy“. Thesis, Massachusetts Institute of Technology, 2002. http://hdl.handle.net/1721.1/29279.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2002.Vita.
Includes bibliographical references (leaves 130-140).
Antibodies have been used as cancer therapeutics for several decades. One area in which this therapy may be improved is the retention time of antibody in the tumor relative to normal tissue. In this Thesis, we have attempted to elucidate the mechanisms that are most influential to improving antibodies as cancer therapeutics. Carcinoembryonic antigen (CEA) has long been identified as a tumor-associated antigen. CEA is also quite stable, with a cell-surface shedding half-life of approximately 7 days. Directed evolution methodology has been utilized to design an antibody fragment with properties that would improve tumor retention. Specifically, antibody engineering methods were used to produce a humanized, extremely high affinity and stable single chain antibody fragment (scFv) against CEA. Several mutant scFv libraries were constructed and screened against soluble CEA with yeast surface display and fluorescent activated cell sorting (FACS). A series of antibodies were engineered that span three orders of magnitude in off-rate improvement. These antibody fragments show excellent stability at physiologically relevant temperatures. In addition, soluble protein expression levels were greatly improved. The final product has a dissociation half-life of approximately 7 days, currently the longest engineered half-life of an scFv against a tumor-associated antigen. Binding and diffusion in micrometastases was also modeled to gain an improved understanding of the quantitative interplay among the rate processes of diffusion, binding, degradation, and plasma clearance in tumor microspheroids.
(cont.) Modeling studies illuminated the importance of targeting stable tumor-associated antigens. The elimination rate of the antigen was of critical importance to the change in the therapeutic effect of antibodies with increasing affinity. The significance of this result in the context of previous experimental studies will be discussed. By affinity maturing an antibody with a dissociation half-life equal to the turnover half-life of the antigen, we have engineered an antibody with effectively irreversible binding to CEA. Differences in retention for the series of scFvs will thus be dominated by the off-rate of the antibody and not the half-life of CEA. With this in mind, the molecules designed in this study can be used to reconcile the issue of affinity's impact on efficacy in tumor therapy.
by Christilyn Paula Graff.
Ph.D.
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Valladão, Maria Luiza de Castro Ramos 1977. „Remodelamento do tumor venéreo transmissível“. [s.n.], 2007. http://repositorio.unicamp.br/jspui/handle/REPOSIP/308603.
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Orientador: Konradin MetzeTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
Made available in DSpace on 2018-08-20T00:01:11Z (GMT). No. of bitstreams: 1 Valladao_MariaLuizadeCastroRamos_D.pdf: 10270983 bytes, checksum: 4313e15091d949287ba12830e233437d (MD5) Previous issue date: 2012
Resumo: O tumor venéreo transmissível canino (TVTC) é transmitido por meio da transplantação de células neoplásicas. O sulfato de vincristina é o agente quimioterápico mais utilizado no tratamento do TVTC. O objetivo deste estudo foi comparar as alterações morfológicas antes da quimioterapia e após uma semana da aplicação de uma injeção intravenosa de sulfato de vincristina. Neste estudo prospectivo, 100 massas tumorais do TVTC de ocorrência natural foram inclusos. Lâminas citológicas coradas com HE, cortes parafinados corados com tubulina e PCNA, cortes para microscopia eletrônica foram preparados pré e pós tratamento. Realizou-se a contagem da taxa de mitoses, da porcentagem de linfócitos e da marcação do PCNA. Também foi feita a análise de imagem computacional da textura nuclear e a análise sintática estrutural do tecido tumoral. A morfometria demonstrou que, após a terapia, houve a diminuição da área, do perímetro, do diâmetro, da densidade óptica integrada e da tonalidade dos agrupamentos nucleares; enquanto houve aumento do "goodness of fit" da dimensão fractal nuclear. Na análise sintática estrutural, observou-se o aumento da distância entre os núcleos. A contagem de mitoses e o índice PCNA não mostraram diferença entre a primeira e a segunda biópsia. Os agrupamentos citoplasmáticos grandes que foram corados com tubulina diminuíram de tamanho após o tratamento e essa alteração talvez se deva à ruptura induzida pela vincristina nos microtúbulos. Em resumo, a quimioterapia com vincristina promoveu profundas alterações no núcleo, no citoplasma e na reorganização estrutural sintática do tumor
Abstract: The canine transmissible venereal tumor (CTVT) is transmitted by transplantation of neoplastic cells. Vincristine sulfate is the most widely used chemotherapeutic agent for the treatment of CTVT. The aim of this study was to compare the tumor morphology before chemotherapy and one week after application of a single intravenous injection of vincristine sulphate. In this prospective study 100 animals with spontaneously occuring CTVT were included. HE-stained cytological imprints, paraffin sections stained by tubulin and PCNA and sections for electron microscopy were prepared from the tumor before and after treatment. Mitotic rate, percentage of lymphocytes and PCNA stained tumor cells were counted. Computerized image analysis of the nuclear texture and syntactic structure analysis were applied. After therapy nuclear morphometry showed decreased area, perimeter and diameter values, diminished integrated optical density and cluster shade of nuclear texture, as well as increased values of "goodness of fit" of the fractal dimension. The nuclei were more distant. Mitotic counting and PCNA index did not differ between the first and second biopsy. Cytoplasmic large tubulin clusters diminished their size during treatment. This finding may be due to the vincristine-induced rupture of microtubules. In summary, chemotherapy with vincristine provides profound changes in the nuclear, cytoplasmic and syntactic structural organization of the tumor
Doutorado
Biologia Estrutural, Celular, Molecular e do Desenvolvimento
Doutor em Fisiopatologia Medica
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Dennie, Joëlle 1970. „NMR imaging of tumor angiogenesis“. Thesis, Massachusetts Institute of Technology, 1997. http://hdl.handle.net/1721.1/43595.
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Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Nuclear Engineering, 1997.Includes bibliographical references (leaves 66-69).
Cancer remains a major medical problem accounting for over 500,000 deaths in the US annually. A common feature of most human tumors is their ability to induce the proliferation of new blood vessels, i.e. angiogenesis. Considerable evidence now exists which demonstrates that these tumor vessels are associated with a distinct range of morphological and physiological properties which are not present in normal tissue vasculature. Several studies now document that in a wide variety of tumor models, average tumor vessels have diameters two times those of normal tissue vessels. NMR techniques based on magnetic susceptibility mechanisms are sensitive to varying sizes of blood vessels. By using gradient echo (GE) and spin echo (SE) pulse sequences and different concentrations of an exogenous contrast agent, it is possible to determine the signal contribution from small versus large vessels by examining the change in T2 and T2* rates ([delta]R2 and [delta]R2*), i.e. the ratio of [delta]R2* to [delta]R2 increases with vessel size. This ratio provides an index for the average size of vessels within a voxel. The central goal of this research was to utilize such a tool in order to obtain a regional picture of the tumor vascular bed. Rats, inoculated with C6 glial cells, underwent an MR imaging series nineteen days after implantation, which comprised conventional SE and GE images prior to and following serial injections of an equilibrium iron oxide contrast agent (MION). Regions within the tumor and in the contralateral normal gray matter were identified. The change in the T2 rate and T2* rate ([delta]R2 and [delta]R2*) were calculated for each region. Since susceptibility contrast mechanisms designed to study the distribution of vessel sizes rely entirely on the compartmentalization of the contrast agent within the vasculature, the first set of experiments was designed to demonstrate the stability of MION to remain within the vasculature, despite the disruption in the blood brain barrier. The second experiments measured [delta]R2 and [delta]R2* as a function of contrast agent concentration and TE. The MR measurements were compared with predicted values of [delta]R2 and [delta]R2* made from histological assessment of vessel sizes and theoretical Monte Carlo simulation results. The steady state measurements of [delta]R2 and [delta]R2* in the first experiments demonstrated that once the maximum contrast agent concentration had been reached, the values of [delta]R2 and [delta]R2* remained stable over 90 minutes, suggesting that MION remains within the vasculature. In the second experiments, significant differences were observed between the tumor and contralateral deep gray matter. Specifically, the ratio of ([delta] R2*/ ([delta]R2 was greater in the tumor than the normal brain, by a factor of 1.9 ± 0.2. From histologic sections and numerical simulations, the corresponding ratio was predicted to be 1.9 ± 0.1. These ratios are suggestive of a greater relative density of large vs small vessels. Maps of the ratio [delta]R2*/[delta]R2 were also produced on a pixel by pixel basis. Regions of high intensity on these maps (indicating a higher ratio of [delta]R2*/[delta]R2) corresponded well with the location of the tumor as determined using conventional images.
by Joëlle Dennie.
S.M.
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Raman, Sundaresan. „Phenotypical Analysis of Tumor Microenvironment“. The Ohio State University, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=osu1354712085.
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Tuijnder, Marcel. „Biological models of tumor reversion“. Paris 7, 2005. http://www.theses.fr/2005PA077085.
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Cahlin, Christian. „Cyclooxygenase activity and tumor progression /“. Göteborg : Departments of Surgery and Transplantation, Institute of Clinical Sciences at Sahlgrenska Academy, University of Gothenburg, 2008. http://hdl.handle.net/2077/18198.
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Åkerman, Maria E. „Targeting and inhibiting tumor angiogenesis /“. Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2005. http://wwwlib.umi.com/cr/ucsd/fullcit?p3166405.
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