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Dissertations / Theses on the topic 'Tumor'
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1
Igney, Frederik. "Tumor Counterattack: Apoptose-vermittelte Immunsuppression durch Tumore." [S.l. : s.n.], 2002. http://www.bsz-bw.de/cgi-bin/xvms.cgi?SWB10283671.
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Cataldo, A. "ANTI-TUMOR ACTIVITY OF CPG-ODN IN OVARIAN XENOGRAFT TUMORS." Doctoral thesis, Università degli Studi di Milano, 2014. http://hdl.handle.net/2434/229558.
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Synthetic oligodeoxynucleotides expressing CpG motifs (CpG-ODN), Toll-like receptor 9 (TLR9) agonists, are able to induce innate/adaptive immune responses and can enhance the antitumor activity of DNA-damaging chemotherapy and radiation therapy in preclinical mouse models.
It was recently reported that peritumoral CpG-ODN treatment in preclinical models of ovarian cancer, activating TLR-9 expressing cells in tumor microenvironment, induces modulation of DNA repair genes and sensitizes cancer cells to DNA-damaging Cisplatin treatment.
In this thesis we investigated whether this treatment induces modulation of miRNAs in tumor cells and their relevance to chemotherapy response. Array analysis identified 20 differentially expressed miRNAs (16 down- and 4 up-regulated) in human IGROV-1 ovarian tumor cells from CpG-ODN-treated mice versus controls. Evaluation of the role of the 3 most differentially expressed miRNAs on sensitivity to Cisplatin of IGROV-1 cells revealed significant increased Cisplatin cytotoxicity upon ectopic expression of hsa-miR-302b (up-modulated in our array), but no increased effect upon reduced expression of hsa-miR-424 or hsa-miR-340 (down-modulated in our array). The impact of expression levels of all 20 differentially expressed miRNAs were associated with time to replase and overall survival probability in two data sets of ovarian cancer patients treated with platinum. It was found that hsa-miR-302b expression was significantly associated with time to relapse or overall survival in these patients. Use of bio-informatics tools identified 19 mRNAs potentially targeted by hsa-miR-302b, including HDAC4 gene, which has been reported to mediate Cisplatin sensitivity in ovarian cancer. Both HDAC4 mRNA and protein levels were significantly reduced in IGROV-1 cells overexpressing hsa-miR-302b. Altogether, these findings indicate that hsa-miR-302b acts as a ‘‘chemosensitizer’’ in human ovarian carcinoma cells and may represent a biomarker able to predict response to Cisplatin treatment. Moreover, the identification of miRNAs that improve sensitivity to chemotherapy provides the experimental underpinning for their possible future clinical use.
In the second part of this thesis we tested the efficacy of CpG-ODN in combination with other possible therapeutic agents in ovarian carcinoma ascites-bearing athymic mice, to mimic clinical treatment situations in advanced human ovarian disease.
Mice injected i.p. with IGROV-1 ovarian cancer cells were treated at different stages of ascites progression for 4 weeks with CpG-ODN alone or in combination with Bevacizumab, Polyinosinic:Polycytidylic acid (Poly(I):Poly(C)), Gefitinib, Cetuximab and Cisplatin.
In mice treated when ascitic fluid began to accumulate, CpG-ODN combined with Bevacizumab, Poly(I): Poly(C) or Gefitinib did not significantly increase Median Survival Times (MST), as compared with that using CpG-ODN alone, whereas MST in mice treated with CpG-ODN plus Cetuximab was significantly increased (>103 days for combination vs 62 days for CpG alone; P = 0.0008), with 4/8 mice alive at the end of the experiment. In mice showing evident and established ascites, evaluated with increase of abdominal volume and body weight (27.9 ± 0.8 g after vs 23 ± 1.1 g before tumor cell injection), treatment with Cisplatin in addition to CpG-ODN/Cetuximab led to significantly increased MST (105.5 days; P = 0.001), with all mice still alive at 85 days, over that using CpG ODN/Cetuximab (66 days), Cetuximab/Cisplatin (18.5 days), Cisplatin (23 days) or saline (16 days). At a very advanced stage of disease (body weight: 31.4 ± 0.9 g), when more than half of control mice had to be sacrificed 6 days after starting treatments, the triple-combination therapy still increased MST (45 days; P = 0.0089) vs controls.
These data indicated that CpG-ODN combination therapies that enhance the immune response in the tumor microenvironment and concomitantly target tumor cells are highly efficacious even in experimental advanced malignancies. Although differences in the distribution of TLR9 in mice and humans and the enrichment of this receptor on innate immune cells of athymic mice must be considered, our results indicate a promising strategy to treat ovarian cancer patients with bulky ascites.
3
Swanson, Kristin Rae. "Mathematical modeling of the growth and control of tumors /." Thesis, Connect to this title online; UW restricted, 1999. http://hdl.handle.net/1773/6764.
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Lu, Dan. "Tumor priming enhances particle delivery to and transport in solid tumors." Columbus, Ohio : Ohio State University, 2006. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1144936804.
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Tai, Kai-chun Dora, and 戴啟真. "Krukenberg tumours of colorectal origin: experience of a tertiary referral centre and review of theliterature." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2010. http://hub.hku.hk/bib/B4562043X.
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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.
7
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, and 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.
10
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
16
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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Siesjö, Peter. "Immunotherapy of rat brain tumors with mutagen induced, cross-reactive tumor cell variants." Lund : Section of Tumor Immunology, Dept. of Cell and Molecular Biology, University of Lund, 1997. http://books.google.com/books?id=TXZrAAAAMAAJ.
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Nakayama, Tomitaka. "MDM2 gene amplification in bone and soft-tissue tumors : association with tumor progression in differentiated adiposetissue tumors." Kyoto University, 1997. http://hdl.handle.net/2433/202202.
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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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Iizuka, Yusuke. "Dynamic tumor-tracking radiotherapy with real-time monitoring for liver tumors using a gimbal mounted linac." Kyoto University, 2016. http://hdl.handle.net/2433/215388.
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Roller, Benjamin Thomas. "A nanoencapsulated visible dye for intraoperative delineation of brain tumor margins." Thesis, Georgia Institute of Technology, 2011. http://hdl.handle.net/1853/42805.
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Brain and central nervous cancer presents a significant clinical burden, accounting for 2.4% of all cancer deaths. High grade glioma is particularly deadly, with 5 year survival times of 35% or less. Traditional treatment includes tumor resection followed by radiation therapy or chemotherapy. Aggressive resection is essential in order to prolong patient life. In fact, several studies have shown that life expectancy increases with increased extent of resection. Extent of resection is burdened by the fact that surgeons must be careful not to remove functional brain tissue.
Resection is incomplete more often than not due to lack of visual cues for the surgeon. He must rely on tactile sensation to distinguish tumor from healthy tissue. Methods such as intraoperative MRI and CT exist, but these require expensive equipment and special training that is not available in all surgical environments. Some laboratories have proposed small molecule dyes to solve this problem, but these are insufficient when used in an invasive tumor model. It was the goal of this research to provide an objective cue in the form of a nanoencapsulated visible dye without the need for additional equipment of changes to the surgery process itself other than injection of the dye.
We hypothesized that the nanocarrier would allow staining of the tumor through passive targeting by taking advantage of the enhanced permeability and retention effect. Once the nanocarriers have reached the desired target, they would not diffuse out into healthy tissue due to their large size compared to small molecule dyes, which readily diffuse out and stain healthy tissue.
To test this hypothesis, we prepared and characterized a liposomal nanocarrier encapsulating Evans blue dye. The nanocarrier was tested for safety in vitro and in vivo, then used to delineate tumor margins in an invasive rat glioma model in vivo. Microscopic analysis was then conducted to ensure only tumor tissue was stained by the nanocarrier. This thesis presents a successful method of tumor border delineation to provide surgeons with positive visual cues without the need for changes in surgical environment or techniques.
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Wang, Min. "Fine mapping and candidate gene analysis of murine lung tumor susceptibility genes." Connect to this title online, 2003. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1054682174.
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Thesis (Ph. D.)--Ohio State University, 2003.Title from first page of PDF file. Document formatted into pages; contains xvi, 150 p.; also includes graphics (some col.) Includes bibliographical references (p. 129-150). Available online via OhioLINK's ETD Center
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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, and 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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Zhu, Quan. "Role of CDP in MMTV transcriptional regulation and tumorigenesis." Access restricted to users with UT Austin EID, 2001. http://wwwlib.umi.com/cr/utexas/fullcit?p3037038.
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Taylor, Charles Dariush. "Structural characterisation and analysis of human cripto-1." Thesis, University of Oxford, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.670042.
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Monteiro, Vasconcelos Ines [Verfasser]. "Epigenetic quantification of tumor-infiltrating T-lymphocytes in epithelial ovarian tumors / Ines Monteiro Vasconcelos." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2014. http://d-nb.info/1052529828/34.
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Wang, Dian. "Mutational Inactivation of The P53 Tumor Suppressor Gene in Chemically-Induced Rat Esophageal Tumors /." The Ohio State University, 1996. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487933245536557.
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Kasnitz, Nadine [Verfasser], and 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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Morano, Josà AntÃnio Carlos Otaviano David. "AvaliaÃÃo dos efeitos da hipertermoterapia por ultrasom associada a agentes antiangiogÃnicos no tratamento do tumor experimental de walker." Universidade Federal do CearÃ, 2009. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=4685.
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CoordenaÃÃo de AperfeiÃoamento de NÃvel SuperiorOs mÃtodos tradicionais de tratamento do cÃncer, como a quimioterapia e a radioterapia, embora sejam eficazes em vÃrios tipos de tumores, encontram freqÃentemente populaÃÃes de cÃlulas neoplÃsicas resistentes, alÃm de apresentarem uma baixa margem de seguranÃa para os pacientes. A utilizaÃÃo da hipertermia associada à quimioterapia e/ou radioterapia jà se encontra fartamente relatada como vantajosa na literatura especializada, principalmente em pacientes portadores de cÃncer em estÃdio avanÃado, submetidos previamente aos mÃtodos clÃssicos de tratamento. A aplicaÃÃo de calor nos tecidos atravÃs de ultrassom contÃnuo torna mais Ãgil Ãste procedimento e com eficÃcia comprovada. O uso dos antiangiogÃnicos tambÃm vem sendo relatado como eficaz na literatura especializada e atualmente, a lista destas substÃncias vem aumentando consideravelmente. O estudo da aÃÃo da hipertermia associada a alguns agentes antiangiogÃnicos tem sido sugerida uma vez que os vasos tumorais ao encontrarem-se dilatados, nÃo promoverÃo a diminuiÃÃo da temperatura no tecido tumoral e, consequentemente, os efeitos desta associaÃÃo serÃo mais intensos do que no tecido normal devendo contribuir para a morte celular. Objetiva-se neste trabalho, avaliar o efeito antitumoral e antiangiogÃnico da hipertermia induzida por US isolada e combinada com etoricoxibe e pegaptanibe,no carcinossarcoma de Walker 256 implantado na tela subcutÃnea do dorso de ratos por meio de utilizaÃÃo do modelo experimental de hipertermoterapia por US assim como o estudo dos efeitos da hipertermia por US isolada e em combinaÃÃo com etoricoxibe e pegaptanibe,na angiogÃnese tumoral.O mÃtodo utilizado para o estudo teve inÃcio com o implante de cÃlulas de tumor de Walker 256 no dorso de ratos Wistar machos. Os animais foram tratados com hipertermia aplicada atravÃs de aparelho de ultrassom, mantida a nÃvel de 45o C durante cinco minutos no terceiro dia apÃs a inoculaÃÃo e tambÃm tratados com etoricoxibe e pegaptanibe por via oral e intraperitoneal respectivamente a partir do dia da inoculaÃÃo. Cada grupo de animais foi submetido a medidas do crescimento tumoral durante o perÃodo de 30 dias, assim como tambÃm à avaliaÃÃo da microdensidade vascular atravÃs de estudo mesoscÃpico fotogrÃfico, validado pelo estudo microscÃpico. A aplicaÃÃo do calor atravÃs de aparelho de ultrasom demonstrou eficiÃncia e agilidade A hipertermia, o etoricoxibe e o pegaptanibe, apresentaram capacidade antiangiogÃnica, expressada tanto pela curva de sobrevida, como pela avaliaÃÃo da microdensidade vascular. Particularmente, a hipertermia isoladamente apresentou um efeito antiangiogÃnico significativo tanto na curva de crescimento tumoral como na diminuiÃÃo da densidade microvascular. A associaÃÃo da hipertermia com o pegaptanibe, demonstrou uma eficiÃncia na diminuiÃÃo da densidade microvascular significativamente maior do que os demais grupos. O modelo de aplicaÃÃo de hipertermia gerada por um aparelho de ultrassom na modalidade contÃnua foi satisfatÃria, demonstrando ter sido efetiva tanto na diminuiÃÃo do crescimento tumoral, como na diminuiÃÃo da densidade microvascular.
The traditional methods of cancer treatment, like the chemotherapy and radiotherapy, even though they are effective in many types of tumours, they find frequently resistant neoplasic cellsâ population, beyond presenting a low security margin to the patients. The hyperthermia use associated to the chemotherapy and radiotherapy are plenty mentioned as profitable in the specialist literature, especially in patients with cancer in advanced stage, submitted previously to the classic methods of the treatment. The tissuesâ heat insertion through the continuous ultrasound becomes the procedure faster and with proved efficacy. The antiangiogenic use also is being related like effective in the specialist literature and, at this moment, the substancesâ list has grown vastly. The study of the hyperthermia action associated to antiangiogenic agents has been suggested, once the tumour vessels are dilated, would not promote the temperature reduction in the tumour vessels and, therefore, the effects of this association would be more intense than in the normal tissue, what might contribute to the death cell. The study objective is to evaluate the antitumor and antiangiogenic effect of the hyperthermia induced by isolated ultrasound and combined with etoricoxibe and pegaptanibe in the 256 Walker carcinossarcoma implanted in the subcutaneous back screen of mouse by using the hyperthermia experimental model by ultrasound, like the hyperthermia effects study by isolated ultrasound and linked with etoricoxibe and pegaptanibe, in the tumour angiogenesis. The method used describes the insertion of 256 Walker Tumour cells in the back of male Wistar mouse. The animals were treated with hyperthermia applied through the ultrasound equipment, kept to a 45Â C level during five minutes in the third day after the inoculation and also treated with etoricoxibe and pegaptanibe by oral and intraperitoneal respectively since the inoculation day. Each animal group was submitted to a tumour growth measurement during a period of 30 days, as well as also a vascular microdensity evaluation through a photographic mesoscopic study, validated by the microscopic study. The heat application through the ultrasound equipment demonstrated efficiency and agility. The hyperthermia, the etoricoxibe and the pegaptanibe showed antiangiogenic capacity, expressed by the over life curve, and also by the vascular microdensity evaluation. Particularly, the isolated hyperthermia showed a significative antiangiogenic effect in the tumour growth curve and also in the decreasing of the micro vascular density. The association between the hyperthermia and the pegaptanibe demonstrated a greater efficiency in the reducing of the micro vascular density than the other groups. The hyperthermia application model generated by the ultrasound equipment in the continuous modality was satisfactory, demonstrating by being effective as much in the reducing of the tumour growth as in the decreasing of the micro vascular density.
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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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ZHENG, ZHI-YONG, and 鄭智勇. "The studies on tumor markers of Chinese colorectal tumors." Thesis, 1988. http://ndltd.ncl.edu.tw/handle/15494181783229187997.
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