Дисертації з теми "Cancer tumer"
Оформте джерело за APA, MLA, Chicago, Harvard та іншими стилями
Ознайомтеся з топ-50 дисертацій для дослідження на тему "Cancer tumer".
Біля кожної праці в переліку літератури доступна кнопка «Додати до бібліографії». Скористайтеся нею – і ми автоматично оформимо бібліографічне посилання на обрану працю в потрібному вам стилі цитування: APA, MLA, «Гарвард», «Чикаго», «Ванкувер» тощо.
Також ви можете завантажити повний текст наукової публікації у форматі «.pdf» та прочитати онлайн анотацію до роботи, якщо відповідні параметри наявні в метаданих.
Переглядайте дисертації для різних дисциплін та оформлюйте правильно вашу бібліографію.
Lale, Shantanu Vijay. "Development of stimuli responsive polymeric nanosystems for cancer therapeutics." Thesis, IIT Delhi, 2016. http://localhost:8080/xmlui/handle/12345678/6999.
Повний текст джерелаMcGinley, Susan. "Sensitizing Tumor Response to Cancer Therapy." College of Agriculture and Life Sciences, University of Arizona (Tucson, AZ), 2008. http://hdl.handle.net/10150/622086.
Повний текст джерелаHoarau, Jessica. "Halfway Between 2D Models and Animal Models : a New Multicellular 3D Spheroid Model Organized to Study Tumor-Endothelium Interactions in Ovarian Cancer." Thesis, Université Paris-Saclay (ComUE), 2019. http://www.theses.fr/2019SACLS111.
Повний текст джерелаOvarian cancer (OC) is the most lethal gynecologic malignancy in developed countries and the fifth cause of death among women. OC is a heterogeneous disease, which is characterized by its late diagnosis (FIGO III and IV stages) and the importance of abdominal metastases often observed at the time of diagnosis. The mainstay of treatment involves complete cytoreductive surgery associated with platinum and taxane-based chemotherapy. Unfortunately, among patients achieving complete clinical remission after completion of initial treatment, 60% with advanced epithelial ovarian cancer (EOC) will relapse within five years.The importance of neo-angiogenesis in tumor formation, growth and dissemination has driven researchers to investigate into alternative strategies. Anti-angiogenic therapies targeting tumor vasculature are now used in combination with standard cytotoxic therapy in the treatment of EOC. Unfortunately, the progress achieved by this approach still offers limited success which can partly be explained by the heterotypic interaction between the tumor and endothelial cells. Evidence suggests a complex cross-talk between ovarian cancer cells (OCCs) and endothelial cells (ECs) that can result in the emergence of a heterogeneous tumoral and endothelial population with different sensitivity to chemotherapy and anti-angiogenic therapies leading to an increase of OCC proliferation and dissemination.The objective of the present study is to investigate the role of ECs and OCCs interactions in the proliferation and chemoresistance of EOC. To model tumor endothelium, we used our model of Akt-activated endothelial cells (E4+ECs). We demonstrated using a 2D co-culture model that activated endothelium induces increased proliferation and chemoresistance in EOC through the activation of Notch signaling. We showed that Notch receptor expression and activation are increased in co-culture and in OCCs resistant to chemotherapy.The accumulation of ascites in the abdomen of an OC patient seems to play a key role in the mechanism of OCC spreading. Detached cancer cells usually float in ascites and form multicellular spheroids. In this context, we developed a new model of organized multicellular 3D spheroid to study tumor-endothelium interactions in a model closer to in vivo conditions. We demonstrated that when cocultured in 3D condition, E4+ECs and OCCs formed organized tumor angiospheres with a core of endothelial cells surrounded by highly proliferating OCCs. We established that AKT activation in ECs was mandatory for the formation of organized angiospheres. Interestingly, in EOC patient ascites, we were able to find structures that were very similar to our angiospheres. In addition, in a retrospective cohort of 59 patients, we showed that ECs were AKT activated in EOC patients which support the importance of AKT activation in EC in EOC. Besides, we demonstrated the importance of FGF2, Pentraxin 3 (PTX3), PD-ECGF and TIMP-1 in angiosphere organization. Finally, we confirmed the role of Notch3/Jagged1 in OCCs-ECs crosstalk for OCC proliferation but also during peritoneum invasion.Altogether, our study illustrates the importance of AKT activated ECs in EOC. In a context of poor results of anti-angiogenic therapies in clinical settings, focusing on vascular normalization in pathological angiogenesis could be more efficient. While AKT is hardly targetable, the genetic characterization of tumors could potentially identify a subset of tumors with aberrant NOTCH signaling that would constitute an ideal target for specific inhibitors. As we move toward personalized and precision medicine, there might be a place for notch inhibition in advanced ovarian cancer in combination with other therapeutic strategies
Stemmer, Kerstin. "Molecular Characteristics of Kidney Cancer." [S.l. : s.n.], 2008. http://nbn-resolving.de/urn:nbn:de:bsz:352-opus-73925.
Повний текст джерелаDacheux, Estelle. "Implication de la protéine onco-suppressive BRCA1 dans la régulation de la traduction." Thesis, Lyon 1, 2013. http://www.theses.fr/2013LYO10077.
Повний текст джерелаBRCA1 is one of the two major genes of breast cancer susceptibility. The numerous binding partners of BRCA1 allow it to participate to several cellular pathways which globally contribute to its cell surveillance capacity. The team in which I performed my PhD identified a new bindind partner of BRCA1, the Poly(A)-Binding Protein 1 and, consequently, a new function of this tumor suppressor, namely, the translation regulation [1]. During my PhD, I studied this new function and try to elucidate if, and how, this function could participates to the BRCA1’s tumor suppressive activity. I first showed that BRCA1 is associated with the ribosomal fraction of the cell, and more precisely, with the subpolysomal fraction, which could indicate that BRCA1 participates to the initiation step of translation. Moreover, our results suggest that BRCA1 could participate to a non canonical initiation complex. Given that BRCA1 is not a canonical translation initiation factor, it is unlikely that BRCA1 regulates the translation of all mRNAs. Our hypothesis is that BRCA1 could regulate the translation of specific mRNAs involved in its various cell surveillance functions. In an attempt to identify the BRCA1 translational targets, we performed a microarray analysis of polysomes-bound mRNAs in MCF7 cells transiently expressing siRNA directed against BRCA1 or control siRNA. We found that, among the translational targets of BRCA1, many indeed encode proteins involved in the same main functions as BRCA1’s. Altogether, our results suggest that the involvement of BRCA1 in translation regulation could be another way by which BRCA1 exerts its tumor suppressor role. Moreover, the analysis of the BRCA1’s translational targets could lead to the identification of new functions for BRCA1 as well as to the discovery of new tumoral markers and therapeutic targets for the BRCA1 mutated patients
Bonneau, Claire. "Étude des mécanismes de récidive métastatique dans les cancers du sein luminaux de stade précoce : impact du microenvironnement tumoral Caractérisation moléculaire des cancers du sein en pratique clinique A subset of activated cancer associated fibroblasts is associated with distant relapse in early luminal breast cancers." Thesis, Sorbonne Paris Cité, 2018. https://wo.app.u-paris.fr/cgi-bin/WebObjects/TheseWeb.woa/wa/show?t=2365&f=17162.
Повний текст джерелаPurpose: Early luminal breast cancers (BC) represent 70% of newly diagnosed BC. Their prognosis is generally favorable but some patients (around 5 to 10% at 10 years) will relapse with distant metastases and most of them will die. Because this dismal prognosis concerns a small number of patients, T1N0 BC have been rarely studied. The aim of this work was to identify the mechanisms of metastatic recurrence in luminal breast cancers T1b-cN0M0 at diagnosis by deciphering characteristics of both epithelial cancer cells and their surrounding tumor microenvironment (TME). Experimental Design: We constituted a cohort of luminal T1b-cN0 BC patients with metastatic recurrence (defined as "cases”) and corresponding "controls" (i. e. patients without metastatic relapse) matched (1:1) to cases on the main known prognostic factors: age, tumor grade and tumor proliferation (assessed by Ki67). Results: We found that properties in both epithelial compartment and TME are indicative of relapse in early luminal breast cancers. In univariate analysis, the loss of differentiation (assessed by the reduced expression of CDH1/E-cadherin) in cancer cells is associated with recurrence, as also predicted by high ROR score using ProsignaTM test. In TME, quantitative and qualitative immunohistochemical analyzes reveals that “cases” are characterized by a significant decrease in CD4+ T lymphocytes and an accumulation of a particular subset of Cancer Associated Fibroblasts (CAF-S1) compared to “controls”, without any other association of T lymphocyte subtypes, B lymphocytes, macrophages or dendritic cells. In multivariate analysis, TME features, in particular CAF-S1 enrichment, remain significantly associated with recurrence, which demonstrates their biological and clinical relevance. Finally, by performing functional analyses, we demonstrated that CAF-S1 pro-metastatic properties are -at least in part- mediated by CDH11/Osteoblast cadherin, consistent with the fact that the bones are a major site of metastases in these patients. Conclusions: Distant recurrence in early luminal BC is strongly associated with TME features, such as the presence of CAF-S1 and their expression of CDH11. This is independent of tumor cells and represents a new prognostic factor of distant relapse in early luminal BC patients. This could justify targeted therapies against CAF-S1 or CDH11 in these cases
Pålsson, Birger. "Tumour marker CA-50 in pancreatic cancer." Lund : Dept. of Surgery, Lund University, 1993. http://catalog.hathitrust.org/api/volumes/oclc/38154714.html.
Повний текст джерелаMuller, Laure. "Modélisation et traitement du signal de rétrodiffusion lumineuse dans les tissus vivants appliques à la détection de bas niveaux de saturation en oxygène : contribution à l'optimisation de la dosimétrie en thérapie photodynamique anticancéreuse." Vandoeuvre-les-Nancy, INPL, 1994. http://www.theses.fr/1994INPL120N.
Повний текст джерелаPayne, 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.
Повний текст джерелаFumagalli, Debora. "Evaluation of tumor heterogeneity in breast cancer." Doctoral thesis, Universite Libre de Bruxelles, 2016. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/229735.
Повний текст джерелаBreast cancer still represents the most frequently diagnosed cancer and the leading cause of cancer-related mortality in women. Death is usually caused by the development of resistance to treatments and the resulting metastatic spread of the disease. Despite the clinical relevance, little is known about the molecular complexity of the disease and its dynamics.Breast tumor heterogeneity has been observed at the level of the histology and the natural history of the disease for a long time, and these differences have served as the basis for disease classification. With the advent of high-throughput technologies, such as gene expression microarrays and massively parallel sequencing, this classification has been refined and a previously unknown genetic complexity has been revealed. Studies implementing these technologies have shown that molecular dif¬ferences exist not only between different breast cancer patients (inter-tumor heterogeneity), but also within the same patient (intra-tumor heterogeneity). Furthermore, intra-tumor heterogeneity could occur either between different regions of a tumor (spatial intra-tumor heterogeneity), or as the result of the molecular evolu¬tion of a tumor over time (temporal intra-tumor heterogeneity). This complexity might have a profound impact on the way breast cancer patients are managed and treated. The research work that I carried out in the Breast Cancer Translational Research Laboratory under the direction of Prof Christos Sotiriou had two main aims. The first was to determine the extent and the clinical implications of intra-tumor heterogeneity in two common clinical scenarios, namely: multifocal breast cancers (MFBCs) and metastatic ER positive/HER2 negative breast cancers. The second was to investigate the potential impact of yet poorly characterized phenomenon, such as RNA editing, in determining inter-tumor heterogeneity. For this purpose, I have conducted three main projects, which resulted in three manuscripts.We showed that:1) The lesions of all the investigated MFBCs shared a common origin. Despite this, and despite having similar pathological features, in up to a third of the patients the lesions of the same MFBC didn’t share any substitution/indels, and inter-lesion heterogeneity was observed for oncogenic mutation(s) in genes such as PIK3CA, TP53, GATA3, and PTEN; 2) When focusing on a defined number of cancer-associated genes, a substantial concordance for mutations and copy number aberrations could be found between primary and matched metastatic lesions of ER positive/HER2 negative breast cancers. Differences between matched pairs could however be found for the level of expressions of few genes. In primary lesions, only the expression levels of few genes and high FGFR1 amplification levels were associated with OS;3) A-to-I RNA editing is a pervasive source of transcriptome variation in breast cancer. In breast and potentially all cancers, A-to-I editing is mainly controlled by two factors, namely 1q amplification and inflammation, both of which are highly prevalent among human cancers. The wide-spread editing observed, in combination with the conservation of editing sites detected across tissues and patients, suggests that there might be clinical and therapeutic implications for a wide range of cancer patients.Our results suggest both that a thorough molecular characterization of multifocal and metastatic breast cancers is important to appreciate their genomic complexity, and that in breast cancer research more relevance should be given to RNA editing, a yet poorly investigated phenomenon that has the potential to impact the development and the evolution of the disease.
Doctorat en Sciences médicales (Médecine)
info:eu-repo/semantics/nonPublished
Ahmed, Atique U. "Targeting cancer through tumor-selective mRNA stabilization." Thesis, Open University, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.441144.
Повний текст джерелаGallerani, Giulia <1986>. "Circulating Tumor Cells Investigation in Esophageal Cancer." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2016. http://amsdottorato.unibo.it/7343/1/gallerani_giulia_tesi.pdf.
Повний текст джерелаGallerani, Giulia <1986>. "Circulating Tumor Cells Investigation in Esophageal Cancer." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2016. http://amsdottorato.unibo.it/7343/.
Повний текст джерелаSilva, Alexandra Isabel Marques da. "Potencial utilização do ácido acetilsalicílico como anticancerígeno." Master's thesis, [s.n.], 2014. http://hdl.handle.net/10284/4867.
Повний текст джерелаA aspirina, cuja substância ativa é o ácido acetilsalicílico, representa um dos medicamentos mais utilizados em todo o mundo. Desde a Idade Média até aos dias de hoje, têm vindo a ser descritas inúmeras propriedades terapêuticas nomeadamente: analgésica, antipirética, anti-inflamatória, anti-plaquetária, entre outras. No presente, para além do seu uso no alívio da dor ligeira a moderada, febre e inflamação, a aspirina assume um importante papel na diminuição do risco de acidentes cardiovasculares. Entretanto, vários ensaios têm vindo a sugerir novos efeitos benéficos da aspirina. Descobertas recentes demonstraram que a aspirina, administrada por vários anos, pode reduzir, a longo prazo, o risco de alguns tipos de cancro, particularmente o cancro colorretal. Várias evidências apoiam a hipótese de que esse efeito é conseguido com doses baixas de aspirina, as mesmas utilizadas na prevenção de eventos cardiovasculares, posicionando a ação antiplaquetária da aspirina no centro de sua eficácia anti-tumoral. Contudo, ainda não há dados suficientes sobre o risco/benefício e, como tal, ainda não foram feitas recomendações definitivas relativamente ao seu uso, sendo portanto, necessários novos estudos para que se possa definir qual a dose mínima efetiva, qual a duração do tratamento, qual a idade para o iniciar e qual a população alvo em que o benefício é superior ao risco. Nesta revisão, irão ser abordados os conhecimentos atuais sobre o papel da aspirina na prevenção do cancro, especialmente o cancro colorretal. Em particular, serão explorados alguns dos possíveis mecanismos responsáveis por este efeito: uns dependentes das prostaglandinas e da ciclooxigenase (COX), nomeadamente da COX-2, e outros provavelmente independentes, destacando novos caminhos para pesquisas futuras. Aspirin, which active substance is the acetylsalicylic acid, is one of the most widely used medications in the world. From the middle Ages to the present day, several therapeutic properties have been described for this molecule, including: analgesic, antipyretic, anti-inflammatory and anti-platelet action, among others. At present, in addition to its use in the relief of mild to moderate pain, fever and inflammation, aspirin plays an important role in reducing the risk of cardiovascular events. Interestingly, other beneficial effects of aspirin have been recently put forward. For instance, new findings have demonstrated that aspirin intake, administered over several years, may reduce the long term risk of certain types of cancer, particularly colorectal cancer. Indeed, it has been argued that such effect may be achieved using small amounts of aspirin (in proportions similar to ones used in the prevention of cardiovascular events), placing the antiplatelet action of aspirin at the center of its anti-tumor efficacy. However, much uncertainty remains concerning the risk/benefit of aspirin usage in cancer prevention and, as such, no definitive recommendations have been made to date. Consequently, further studies are crucially needed so that it can be defined the minimum effective dose, duration of treatment, what age to start and what the target population in which the benefit is greater than the risk. In this review, it will be considered the current knowledge regarding the role of aspirin in cancer prevention, with a special focus on colorectal cancer. In particular, it will be explored some of the possible mechanisms responsible for this effect while highlighting new paths for future research.
Grillet, Fanny. "Identification et caractérisation des cellules tumorales circulantes dans le cancer colorectal." Thesis, Montpellier, 2015. http://www.theses.fr/2015MONT3510.
Повний текст джерелаLiver or lung metastases represent a poor prognosis in colorectal cancer patients and better understanding tumor spreading became essential to improve patient care. Circulating tumor cells (CTC) is considered as a promising tool, both as prognostic marker and as tool to study mechanisms involved in metastasis development. CTCs are rare and heterogeneous and remain poorly characterized especially in colorectal cancer. It is accepted that at least some of the CTC have a tumor initiating cell (TIC) phenotype that could be responsible for metastasis, chemoresistance and consequently lead to relapse. A deep characterization of CTC became thus an urgent unmet need. The aim of this work was to identify and characterize CTC with TIC properties in colorectal cancer, on the basis of their functional properties. To reach this aim, we established for the first time and characterized CTC lines from blood sample of colorectal cancer patient, and we also developed an orthotopic xenograft mouse model in which tumoral cells are circulating in the blood
Calixto, João Paulo Duarte. "Concentration of tumor biomarkers using aqueous biphasic systems." Master's thesis, Universidade de Aveiro, 2015. http://hdl.handle.net/10773/15353.
Повний текст джерелаAccording to the World Health Organization, around 8.2 million people die each year with cancer. Most patients do not perform routine diagnoses and the symptoms, in most situations, occur when the patient is already at an advanced stage of the disease, consequently resulting in a high cancer mortality. Currently, prostate cancer is the second leading cause of death among males worldwide. In Portugal, this is the most diagnosed type of cancer and the third that causes more deaths. Taking into account that there is no cure for advanced stages of prostate cancer, the main strategy comprises an early diagnosis to increase the successful rate of the treatment. The prostate specific antigen (PSA) is an important biomarker of prostate cancer that can be detected in biological fluids, including blood, urine and semen. However, the commercial kits available are addressed for blood samples and the commonly used analytical methods for their detection and quantification requires specialized staff, specific equipment and extensive sample processing, resulting in an expensive process. Thus, the aim of this MSc thesis consisted on the development of a simple, efficient and less expensive method for the extraction and concentration of PSA from urine samples using aqueous biphasic systems (ABS) composed of ionic liquids. Initially, the phase diagrams of a set of aqueous biphasic systems composed of an organic salt and ionic liquids were determined. Then, their ability to extract PSA was ascertained. The obtained results reveal that in the tested systems the prostate specific antigen is completely extracted to the ionic-liquid-rich phase in a single step. Subsequently, the applicability of the investigated ABS for the concentration of PSA was addressed, either from aqueous solutions or urine samples. The low concentration of this biomarker in urine (clinically significant below 150 ng/mL) usually hinders its detection by conventional analytical techniques. The obtained results showed that it is possible to extract and concentrate PSA, up to 250 times in a single-step, so that it can be identified and quantified using less expensive techniques.
De acordo com dados disponibilizados pela Organização Mundial de Saúde, cerca de 8,2 milhões de pessoas morrem anualmente com cancro. A elevada taxa de mortalidade associada ao cancro resulta da maioria dos pacientes não efetuar exames de rotina e porque a manifestação dos sintomas, na maioria dos casos, acontece quando o paciente já se encontra numa fase avançada da doença. Atualmente, o cancro da próstata representa a segunda maior causa de morte entre indivíduos do sexo masculino em todo o mundo. Tendo em conta que não existe cura para casos avançados de cancro da próstata, a estratégia passa por um diagnóstico precoce que permita aumentar a taxa de sucesso dos tratamentos. O antigénio prostático específico (PSA) é um biomarcador importante do cancro da próstata que pode ser detetado em fluidos biológicos, nomeadamente sangue, urina e sémen. No entanto, os kits comerciais disponíveis utilizam amostras de sangue e os métodos analíticos normalmente utilizados na sua deteção e quantificação requerem pessoal especializado, equipamento específico e um processamento extensivo das amostras, resultando em processos com um elevado custo associado. Assim, o objetivo deste mestrado passou por desenvolver um método simples, eficiente e menos dispendioso para a extração e concentração de PSA a partir de amostras de urina utilizando sistemas aquosos bifásicos (SAB) constituídos por líquidos iónicos. Numa fase inicial, determinaram-se os diagramas de fases de um conjunto de sistemas aquosos bifásicos constituídos por um sal orgânico e por líquidos iónicos. Em seguida, avaliou-se a capacidade dos mesmos para a extração do PSA. Os resultados obtidos demonstram que, nos sistemas em estudo, o antigénio prostático específico é totalmente extraído para a fase rica em líquido iónico num único passo. Por fim, averiguou-se a aplicabilidade dos SAB estudados para a concentração do PSA a partir de soluções aquosas e de urina. A baixa concentração deste biomarcador na urina (clinicamente significativo abaixo de 150 ng/mL) dificulta a sua deteção através de técnicas analíticas convencionais. Os resultados obtidos demonstraram que é possível extrair e concentrar PSA até 250 vezes, numa única etapa, sendo este detetável através de técnicas menos dispendiosas.
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.
Повний текст джерелаCarvalho, Mafalda Barroso. "Mecanismos virais no Cancro da Próstata: influência do vírus XMRV no aparecimento da doença." Master's thesis, [s.n.], 2013. http://hdl.handle.net/10284/4076.
Повний текст джерелаIntrodução – O cancro da próstata tem tido uma enorme prevalência a nível mundial, justificando um elevado número de estudos não só na procura de novos tratamentos mais eficazes como também dos agentes que causam esta patologia, visto ser essencial saber a sua origem para a introdução de estratégias de prevenção. As causas que levam ao seu aparecimento são ainda desconhecidas, embora se saiba já a influência de alguns fatores, tais como a dieta, a idade, os antecedentes familiares, entre outros. Algumas linhas de investigação têm proposto uma hipótese que envolve alguns vírus na etiologia do cancro da próstata, tal como acontece noutros tipos de cancro, tendo como exemplo no cancro do colo do útero com o vírus do papiloma humano. Objetivos – Esta dissertação visa efetuar uma revisão com atualização do conhecimento científico sobre os mecanismos víricos que possam ser considerados como uma das causas do cancro da próstata. Material e métodos – Realizou-se uma pesquisa bibliográfica que incidiu na pesquisa eletrónica de numerosos artigos de jornais e revistas científicas e clínicas e principalmente na base de dados Medline, com interface de pesquisa Pubmed. Efetuou-se uma análise quantitativa e qualitativa dos agentes virais relacionados com o cancro da próstata descritos na literatura. Resultados e discussão – Na literatura, o vírus mais associado ao aparecimento do cancro da próstata é o vírus XMRV. Vários mecanismos de ação foram propostos como forma de infetar os tecidos humanos, principalmente as células da próstata. A presença de mutações no gene RNAseL, tal como uma preferência local por determinados locais de integração levando a uma influência andrógena foram mecanismos defendidos por vários autores. Uma possível transmissão sexual e uma ligação do vírus indireta à tumorigénese apresentam uma menor incidência de citação, mas que não deve ser ignorada. Foram identificados fármacos que poderiam ser utilizados numa terapia contra este vírus, tal como fatores de restrição existentes no humano que impedem a replicação viral por parte de XMRV. Conclusão – Há um elevado número de artigos que defendem uma relação causal entre o vírus XMRV e o cancro da próstata. Contudo, muitos outros autores sugerem que este vírus em humanos seja encontrado apenas devido a contaminação laboratorial. Introduction – Prostate cancer´s worldwide prevalence has justified a high number of studies not only seeking new, more effective treatment but also concerning the pathogenesis since it is of utmost importance reconnaissance of its underlying causes in order to apply preventing measures. Those causes are yet unknown even though some factors influence such as diet, age or family history. Some research have set forward a hypothesis where some viruses take part in prostate´s cancer etiology, similar to other kinds of cancer like the uterine cancer with the HPV. Objectives – The dissertation here presented aims to review the scientific updates on viral mechanisms which are considered as a potencial cause for prostate cancer. Methods and materials – A bibliographical research was conducted with particular focus on online scientific and clinical journals and magazines, using primarily Medline database through Pubmed research interface. A quantitative and qualitative analyses of the prostate cancer related viral agents described in literature was made. Results and Discussion – Literature shows the XMRV as being the virus most associated with prostate cancer. Several mechanisms were purposed for the infection events of human tissue, particularly prostate cells. The presence of mutation on the RNAseL gene and a local preference by determined integration spots leading to an androgenic influence were mechanisms defended by several authors. A possible sexual transmission and an indirect link of the virus to the tumorgenesis are fewer times presented but its significance should not be ignored. Drugs to be used in therapy against XMRV were identified as well as restriction factor present in humans wich stop its replication. Conclusion- There is a high number of articles defending a causal relation between XMRV and prostate cancer. Nevertheless, many authors suggest this virus is only found in humans due to laboratorial contamination.
Mendoza, Erin. "Role of p53 in Adaptation to the Tumor Microenvironment." Diss., The University of Arizona, 2010. http://hdl.handle.net/10150/204113.
Повний текст джерелаMook, Olaf Roger Franciscus. "Tumor development of colon cancer in rat liver." [S.l. : Amsterdam : s.n.] ; Universiteit van Amsterdam [Host], 2004. http://dare.uva.nl/document/88454.
Повний текст джерелаHo, Victor Wing Heng. "Manipulating the tumor microenvironment to slow cancer growth." Thesis, University of British Columbia, 2012. http://hdl.handle.net/2429/42239.
Повний текст джерелаShun, Kitty. "Study of two putative prostate cancer tumor markers." Thesis, McGill University, 2006. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=111937.
Повний текст джерелаEduardo, Rodrigo. "Exploring Tumor Macrophage Interaction in Anaplastic Thyroid Cancer." Master's thesis, Universidade Nova de Lisboa. Instituto de Tecnologia Química e Biológica António Xavier, 2019. http://hdl.handle.net/10362/130111.
Повний текст джерелаN/A
Shahi, Thakuri Pradip. "MODELING ANTI-CANCER DRUG RESISTANCE USING TUMOR SPHEROIDS." University of Akron / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=akron1574725861735168.
Повний текст джерелаDonald, Carlton Dewitt. "Metastatic characteristics of tumor progression in Prostate Cancer." DigitalCommons@Robert W. Woodruff Library, Atlanta University Center, 1995. http://digitalcommons.auctr.edu/dissertations/3299.
Повний текст джерелаPetty, 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.
Повний текст джерелаMehrara, Esmaeil. "Quantitative analysis of tumor growth and response to therapy /." Göteborg : Department of Radiation Physics, University of Gothenburg, 2010. http://hdl.handle.net/2077/21548.
Повний текст джерелаProkop, Katherine Jane. "Cell Death Characterization In Tumor Constructs Using Irreversible Electroporation." Thesis, Virginia Tech, 2013. http://hdl.handle.net/10919/51655.
Повний текст джерелаMaster of Science
Silveira, Willian Abraham da. "Genetic profile analysis of tumor stem cells in locally advanced breast cancer." Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/17/17145/tde-05012016-144854/.
Повний текст джерелаINTRODUÇÃO: O cancer de mama é no mundo o câncer mais comum em mulheres e a disseminação metastática é o principal fator relacionado com a morte pela doença. Acreditasse que as células tronco do câncer de mama - bCSC, na sigla em inglês e definida neste trabalho com a população ALDH1high/LIN-/ESA+ - é responsável pela metástase e pela quimioresistência. O objetivo deste trabalho é encontrar genes que são essenciais para o controle do fenótipo das bCSC, em particular fatores de transcrição. MATERIAIS E MÉTODOS: Nesse trabalho nós utlizamos dois grupos de datasets com dados do transcriptoma, o grupo de datasets de descoberta contém um dataset gerado por nós com 3 amostras pareadas comparando as bCSC com o tumor total (My Data - bCSC/Bulk dataset), um dataset com 8 amostras pareadas comparando as bCSC com as células cancerígenas (Wicha - bCSC/CC dataset) e um dataset com 115 amostras de tecido de câncer de mama (Clinical Response dataset). O segundo grupo, grupo de validação, contém o dataset BRCA-TCGA com 621 amostras, as 4142 amostras de câncer de mama da ferramenta Kmplot, as 17 amostras humanas primárias do subtipo BasL e sua informação sobre a geração, ou não, de tumores em camundongos imunosuprimidos e a análise de linhagens celulares (MF10A e HMLE). Para a análise dos dataset utilizamos o test-t pareado no pacote Limma da liguagem R, o algoritmo ARACNE para a inferência de regulons no dataset Clinical Response, a análise MRA-FET para definir os Reguladores Mestres para o fenótipo das bCSC e a análise GSEA para identificar o significado biológico de nosso achados nos diferentes datasets. RESULTADOS E DISCUSSÃO: Nós identificamos 12 TFs como reguladores mestres, com 9 deles formando duas redes altamente conectadas, uma positivamente relacionada ao fenótipo bCSC formada por SNAI2, TWIST, PRRX1, BNC2 e TBX5 com seus regulons, e definida aqui como a rede de transcrição mesenquimal, e uma rede correlacionada negativamente, formada por SCML4, ZNF831, SP140 e IKZF3, definida aqui como a rede de transcrição da resposta imune e totalmente desconhecida da literatura no contexto do câncer de mama. Embora ainda com fraca evidencia, ZEB1 para controlar as duas redes e ser responsável pela expressão de ALDH1 e dos 3 TFs restantes: ID4, HOXA5 e TEAD1. Como mostram seus nomes, e independente do dataset, do subtipo molecular ou da plataforma utilizada, a rede de transcrição mesenquimal, parece ser responsável pela manutenção do fenótipo de células tronco cancerígenas e a rede de transcrição da resposta imune pela resposta imune adaptativa ao tumor e a um bom prognóstico para as pacientes. CONCLUSÃO: Nós encontramos e descrevemos duas redes de fatores de transcrição que parecem controlar o fenótipo das bCSC, uma delas totalmente desconhecida até agora e relacionada a um bom prognóstico. Nosso achados possuem um claro potencial para uso clínico.
mattei, gianluca. "Tumor Microenvironment: Bioinformatics and Systems Biology Approaches." Doctoral thesis, Università di Siena, 2019. http://hdl.handle.net/11365/1070301.
Повний текст джерелаTeinturier, Romain. "Étude des fonctions biologiques et oncosuppressives du gène MEN1 dans le cancer de la prostate et du sein, et son implication dans la régulation de l'expression des récepteurs nucléaires." Thesis, Lyon, 2017. http://www.theses.fr/2017LYSE1082/document.
Повний текст джерелаFor a long time, mutations of the MEN1 gene have been known to be responsible of the Multiple Endocrine Neoplasia type 1 (MEN1 syndrome), a hereditary disease affecting mainly endocrine organs. Recent advances highlighted the involvement of the MEN1 gene in the development of the breast cancer and prostate cancer. Nevertheless, the role played by the MEN1 gene in prostate cancer still remains unclear, described as on oncogene by some studies, or as a tumor suppressor by others. To further adress this issue, we generated a novel and inductible mouse model, Men1F/F-Nkx3.1Cre-/+, in which the Men1 gene can be specifically disrupted in luminal prostatic cells upon tamoxifen injection. Anatomopathologic examination of our model showed that the Men1 gene disruption accelerate the tumorigenesis in the prostatic gland compared to the control mice. Moreover, molecular analyses showed that the expression of androgen receptor (AR) decreased in Men1-deficient cells. In vitro study perfomed in prostate cancer cell lines showed that menin protein encoded by the Men1 gene is involved in the transcriptionnal regulation of AR.Similarly, my work showed that menin protein also involved in the transcriptionnal regulation of the estrogen receptor alpha (ER?) expression, through its binding on the promoter of the ER??gene. Moreover, clinical study revealed that decrease in menin expression correlates with the occurrence of luminal B subtype of breast cancer, in which ER??expression is reduced. Thus this thesis work, allowed to better characterized the oncosuppressive role of the Men1 gene in the prostatic gland. This work, also highlighted for the first time the involvement of menin protein in the regulation of nuclear receptor expression, in prostate and breast cancer
Lexander, Helena. "Protein expression in prostate cancer /." Stockholm, 2006. http://diss.kib.ki.se/2006/91-7140-617-4/.
Повний текст джерелаSvanberg, Frida, and 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.
Повний текст джерелаBackground: 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.
Tachijian, Nataly. "The effect of deactivation or silencing of tumor stroma with angiogenesis inhibitor on malignancy of tumor metastases." Thesis, Uppsala universitet, Institutionen för farmaceutisk biovetenskap, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-445622.
Повний текст джерелаChau, Wing-ka, and 周穎嘉. "Characterization of ovarian tumor-initiating cells and mechanisms of chemoresistance." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2013. http://hdl.handle.net/10722/197834.
Повний текст джерелаpublished_or_final_version
Biological Sciences
Master
Master of Philosophy
Singh, Sunil. "Engineered Organotypic Breast Tumor Model for Mechanistic Studies of Tumor-Stromal Interactions and Drug Discovery." University of Akron / OhioLINK, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=akron1616940345310981.
Повний текст джерелаJansson, Agneta. "Molecular alterations in colorectal cancer /." Linköping : Univ, 2002. http://www.bibl.liu.se/liupubl/disp/disp2002/med743s.pdf.
Повний текст джерелаAtieh, Youmna Marie Lyne. "Interplay between cancer cells and cancer-associated fibroblasts in tumor invasion and metastasis formation." Thesis, Paris 6, 2017. http://www.theses.fr/2017PA066140/document.
Повний текст джерелаCancer-associated fibroblasts (CAFs) are the most abundant cells of the tumor stroma. Their capacity to contract the matrix and induce invasion of cancer cells has been well-documented. However, it is not clear if CAFs remodel the matrix by other means (degradation, matrix deposition or stiffening). This project demonstrates that CAFs induce cancer cell invasion through assembly of FN into the matrix. CAFs assembled fibronectin (FN) mainly via integrin α5 but integrin αvβ3 was necessary for initial mechanosensing and fibrillar adhesion formation. In the absence of FN, contractility of the matrix by CAFs is preserved. When degradation is impaired, CAFs retain the capacity to induce invasion in a FN-dependent manner. In all cases, the levels of expression of integrin β3 and the amount of assembled FN was directly proportional to the invasion induced by fibroblast populations. Our results highlight FN assembly and integrin β3 as new hallmarks of CAFs. We also noticed that cancer cells migrate towards CAFs suggesting a possible chemotactic response. Using Dunn’s chemotaxis chamber, we found that cancer cells migrate along a gradient of CAF-conditioned media and a gradient of fibronectin. Finally, orthotopic injections of cancer cells and CAFs in the colon wall of mice revealed that CAFs stimulate metastasis of cancer cells to the liver. In conclusion, our data show that CAFs promote cancer cell invasion by depositing fibronectin that can guide cancer cells favoring metastasis formation
Castellana, Donatello. "Tumor-derived microvesicles in cancer progression : In vitro study in a prostate cancer model." Université Louis Pasteur (Strasbourg) (1971-2008), 2008. http://www.theses.fr/2008STR13034.
Повний текст джерелаThe plasma membrane plays a pivotal role in a large number of physiological processes. After cellular stimulation, externalization of PS in the exoplasmic leaflet of plasma membrane is followed by the shedding of membrane microvesicles (MV) in almost all cell types. MV composition reflect the antigenic profile of cells which they originate from, depending on the stimulus apply. Tumour microenvironment is highly enriched in MV shed from cells infiltrating the tumour tissue. Fibroblasts are associated with tumour cells at all stages of cancer progression. Focusing on fibroblasts implication in cancer, we propose an in vitro model in which cancer and normal cells communicate each other via MV. The aim of this study is to elucidate a mechanism, in which prostate cancer cells influence the behaviour of normal stromal cells that in turn affect the aggressiveness of carcinoma cells by mutual MV shedding, promoting or support the creation of a niche favourable for tumour development
Lara, Ana. "FDG tumor volumetric parameters and outcome in lung cancer and head and neck cancer." Thesis, Boston University, 2012. https://hdl.handle.net/2144/12464.
Повний текст джерелаLung cancer (LC) is the leading cause of cancer mortality worldwide and second most common type of cancer in the United States in both genders. Moreover, Head and neck cancer (HNC) is the sixth most common cancer worldwide and 4% of all malignancies in the United States. The role of FDG-PET-CT has recently increased in oncology for diagnosis, treatment monitoring and patient prognosis. FDG Metabolic parameters sued to assess patient care include maximum standard uptake value (SUVmax), metabolic tumor volume (MTV), and total glycolytic activity. This study attempts to prove FDG-metabolic parameters reliability in LC and HNC patients before and after treatment among readers with different levels of experience. Three readers, 2 experienced and 1 inexperienced, read before and after treatment scans of 74 FDG-PET-CT scans from 13 lung cancer patients and 24 head and neck cancer patients. Lesion location was provided beforehand and reliability was tested using intra-class correlation coefficients (ICC) and ANOVA analysis. For every case, ICC was >0.81 (almost perfect agreement) among all readers and ANOVA showed no statistical significance (p>0.05) on the any of the measurements among all readers as well. We concluded that FDG-PET-CT metabolic parameters (SUVmax, MTV, and TGA) are reliable measurements for treatment response in LC and HNC patients and are independent of reader experience as long as lesion location is provided. These parameters have been found to accurately correlate with tumor behavior and patient prognosis; therefore, reliability on its accurate measurement provides strength to FDG-PET-CT as an imaging modality of choice for oncology patients.
Kassouf, Toufic. "Rôle de la tyrosine kinase Syk, un candidat suppresseur de tumeur, dans l'adhérence intercellulaire et l’intégrité épithéliale de la glande mammaire." Thesis, Montpellier, 2016. http://www.theses.fr/2016MONT3518.
Повний текст джерелаThe spleen tyrosine kinase (Syk) is a cytoplasmic protein kinase involved in immune-response signaling. Our team showed for the first time that Syk is also expressed in mammary epithelial cells and that its expression is lost during acquisition of an invasive/metastatic phenotype. Syk acts as a tumor and metastasis suppressor in breast cancer xenograft models. Clinical studies corroborated that loss of Syk expression is correlated with a decreased survival and an increased risk of metastasis development (poor prognosis) in breast cancer and other carcinomas. Using a quantitative phospho-proteomic SILAC approach in breast cancer cells, our group identified new potential Syk substrates. Interestingly, many proteins are involved in intercellular adhesion (E-cadherin/catenin) and epithelial polarization (eg ZO3, occludin, claudin-3). These proteins are localized at the adherens and tight junctions and are known as signaling platforms and components often presenting a tumor suppressor function.In this thesis I mainly focused on:(i) the role of the Syk kinase activity in the regulation of the E-cadherin/catenin complex and(ii) the consequences of the conditional Syk knockout in the mouse mammary gland on breast development and tumorigenesis.Using in vitro kinase assays, we demonstrated that E-cadherin (E-Cdh) and different catenins are direct Syk substrates. The phosphorylated tyrosine residues were identified by mass spectrometry and corresponding phospho-specific antibodies were generated. By immunofluorescence, we observed that endogenous Syk and E-Cdh colocalize at adherens junctions (AJ) and that Syk overexpression stimulates Syk-dependent phosphorylation of E-cadherin and different catenins at AJ. Immunoprecipitation experiments indicate phosphorylated E-cadherin and catenin proteins are associated in a complex. Using functional tests, Syk knockdown by shRNA in breast cancer cells partially inhibited intercellular re-aggregation (2D/3D) and increased cell invasion, migration and 3D-growth in Matrigel. Conversely, Syk overexpression inhibited migration and invasion and promoted intercellular adhesion. Thus, Syk seems to strengthen the intercellular junctions and the integrity of the epithelium via the phosphorylation of the E-cadherin/catenin complex of which its molecular mechanisms were explored. This could be a major mechanism responsible for its anti-invasive activity.These in vitro observations were subsequently extended to an integrated mouse model. As the homozygous SYK gene knockout is lethal; we developed a conditional Syk deletion model in the murine mammary gland (Syk-flox:WAP-Cre).This model allowed us to study the role of Syk in the development and physiology of the mammary gland during lactation and involution, the Syk-negative glands showing developmental defects. On a long-term basis, it also allows to assess the involvement of Syk in the formation and progression of breast cancer in aging cKO Syk mice, bred or not with transgenic mice expressing the MMTV-Neu / Her2 oncogene.Whether Syk is a bona fide tumor suppressor is a crucial issue as Syk inhibitors are being evaluated in clinical studies for the treatment of rheumatoid arthritis. Identification of the signaling pathways governed by Syk could lead to the development of new therapies targeting these proteins and blocking tumor development and progression
Pedrosa, Ana Rita Ponce Álvares de Águeda. "The role of Jagged1 in adult angiogenesis and in solid tumor development." Doctoral thesis, Universidade de Lisboa. Faculdade de Medicina Veterinária, 2016. http://hdl.handle.net/10400.5/10698.
Повний текст джерелаJagged1 (Jag1) is a Notch signaling ligand, which has been described as essential for developmental angiogenesis and to play an important role in several aspects of tumor biology. However the underlying mechanism related to Jagged1/Notch signaling still remain incompletely understood. Therefore this thesis analyzed Jagged1 driven Notch signaling enrolment in adult angiogenesis settings, and in tumor development. To address the role of endothelial Jag1 in physiological and tumoral angiogenesis, endothelial-specific Jag1 mutants driven angiogenic phenotypes were assessed in skin wound healing and in transplanted tumors and prostatic autochthonous tumor growth, respectively. An extensive transcription and expression analysis of Notch signaling members in the tumorigenic development of the mouse prostate was also performed to identify ectopically expressed Notch members. Lastly, the therapeutic potential of an Anti-Jagged1/2 antibody in mouse prostate cancer was evaluated. Altogether, results presented here demonstrate that Jagged1 is a pro-angiogenic ligand due to its ability to antagonize Dll4/Notch1 mediated signaling. It also has a pro-maturation function by both endothelial Notch4 and perivascular Notch3 mediated signaling. Both these functions contribute to accelerated wound healing and tumor growth, by inducing a more functional vasculature. Moreover, we have identified a new angiocrine function for endothelial Jagged1, mediated through Notch3/Hey1 activation in tumor cells. Finally, we have demonstrated that either by mediated endothelial-specific angiocrine function or by tumor cells mediated Jagged1 ectopic expression, this ligand regulated tumor cell proliferation, apoptosis, de-differentiation, epithelial-to-mesenchymal transition and cancer stem-like cells proliferation and survival. Ultimately, we have demonstrated that blocking Jagged-mediated Notch signaling inhibited development and progression of mouse prostate cancer and therefore constitutes a promising therapeutic approach in prostate cancer treatment.
RESUMO - Avaliação do papel do ligando Jagged1 na regulação da angiogénese do adulto e no desenvolvimento de tumores sólidos - A via Notch é uma via de sinalização intercelular altamente conservada que está envolvida na determinação do destino, e na regulação da proliferação e diferenciação celulares. Jagged1 é um ligando desta via, que tem sido descrito como essencial ao processo de angiogénese durante o desenvolvimento embrinário e que desempenha um papel crucial em diversos aspectos de biologia tumoral. No processo do desenvolvimento angiogénico da retina, Jagged1 foi descrito como tendo um efeito contrário ao de outro ligando da via, o Dll4, mas esta interacção continua por demonstrar noutros contextos angiogénicos. Além de ser expresso na vasculatura, Jagged1 também é detectado em células epiteliais de vários órgãos. Em tumores já foi descrito que a expressão epitelial de Jagged1 aumenta ao longo do desenvolvimento tumoral. Jagged1 é desta forma considerado um marcador de mau prognóstico e de elevado potencial metastático em diversos tipos de cancro, nomeadamente da mama e da próstata. No entanto, o mecanismo intrínseco de sinalização Jagged1/Notch nos contextos acima referidos ainda permanence pouco compreendido. Como tal, o trabalho apresentado nesta tese descreve o papel do ligando Jagged1 na regulação da angiogénese fisiológica e sua interacção com o ligando Dll4. Descreve ainda o seu papel na angiogénese tumoral do adulto, no desenvolvimento de tumores da próstata e finalmente o potencial terapêutico do bloqueio dos ligandos Jagged no tratamento do cancro da próstata. Para investigar o papel do ligando Jagged1 no processo angiogénico do adulto recorreu-se ao uso de mutantes endoteliais específicos de ganho e perda-de-função de Jag1 (eJag1OE e eJag1cKO, respectivamente) num modelo de cicatrização de feridas cutâneas. Ainda neste contexto, para investigar as interacções entre os dois ligandos Notch, Jagged1 and Dll4, os mesmos modelos genéticos foram combinados com inibição farmacológica de Dll4 ou Jagged1, respectivamente. Além disso, os mesmos mutantes endoteliais específicos foram ainda utilizados na investigação do papel do ligando Jagged1 na angiogénese tumoral. Para este fim recorreu-se a dois modelos diferentes de tumores no ratinho: o modelo de tumores transplantados subcutaneamente de células Lewis Lung Carcinoma (LLC) e o modelo autóctone de tumor da próstata murino- Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP). Em relação aos processos angiogénicos foram avaliados nos diferentes mutantes, e combinações, diversos parâmetros tais como: densidade, maturidade, funcionalidade e permeabilidade vasculares. Simultaneamente, as populações endoteliais e perivasculares dos diferentes mutantes foram isoladas e efectuada uma análise específica de transcrição de genes envolvidos na regulação da angiogénese nestes tipos celulares. Na avaliação do contributo do ligando Jagged1 expresso no endotélio para o desenvolvimento de tumores da próstata foram ainda analisados os pesos da próstata nos términos das experiências, as lesões classificadas histológicamente bem como outros aspectos de biologia tumoral, tais como proliferação, apoptose e diferenciação celulares e transição epitélio-mesenquimal. Foi também efectuada uma análise da transcrição e expressão dos membros da via de sinalização Notch, incluindo ligandos (Dll1, 3, 4 e Jagged1 e 2), receptores (Notch1-4) e efectores (Hes1, 2, 5 e Hey1, 2, L), em próstatas de ratinhos saudáveis e de ratinhos TRAMP. Esta análise foi efectuada para descrever a dinâmica dos membros da via de sinalização Notch na tumorigénese da próstata de forma a poder identificar membros ectopicamente expressos na próstata tumoral quando comparados com a próstata normal. Foram ainda isoladas as diferentes subpopulações celulares da próstata, basal, luminal e do estroma e os seus perfis transcripcionais comparados entre próstatas normais e com lesões tumorais (TRAMP). Por fim, avaliou-se o potencial terapêutico de um anticorpo anti-Jagged1/2 no tratamento do cancro da próstata, administrando um anticorpo bloqueador anti-Jagged1/2 aos ratinhos TRAMP. Estes ensaios terapêuticos foram realizados em duas janelas temporais distintas: numa fase precoce do desenvolvimento de tumores da próstata, das 12 às 18 semanas de idade e numa fase mais tardia, das 18 às 24 semanas de idade, simulando uma detecção precoce e tardia da doença nos humanos. A eficácia terapêutica foi avaliada pelos pesos da próstata no término da experiência, classificação histopatológica das lesões, análise da vasculatura, proliferação, apoptose e diferenciação celulares, alterações nos compartimentos celulares da próstata, transição epitélio-mesenquimal, e alterações da população de células cancerosas estaminais (CSCs). Nestes trabalhos foram utilizadas técnicas de imunofluorescência, imunohistoquímica, “fluorescent associated cell sorting” (FACS), e “quantitative real time PCR” (qRT-PCR). Colectivamente, os resultados aqui apresentados demonstram que Jagged1 é um ligando pró-angiogénico em contextos de angiogénese do adulto, tanto fisiológica como tumoral. No modelo de cicatrização de feridas foi demonstrado que os mutantes de ganho-de-função (eJag1OE) exibiam um processo de cicatrização de feridas cutâneas e de desenvolvimento de tumores sólidos acelerado, relativamente aos respectivos controlos, enquanto os mutantes de perda-de-função exibiam o fenótipo oposto. Estas diferenças fenotípicas entre os mutantes deveram-se aos primeiros exibirem uma vasculatura mais densa, com maior número de células de suporte, e portanto mais funcional e menos permeável, enquanto que os segundos exactamente o oposto. O papel pró-angiogénico do ligando Jagged1 foi também demonstrado ser exercido através de complexas interações com diferentes receptores Notch. Utilizando o modelo de cicatrização de feridas foi demonstrado que Jagged1 presente no endotélio regula negativamente a transcrição e activação de Notch1, e portanto bloqueia a activação de Notch1 mediada por Dll4. Ao contrário do que acontece com Notch1, foi também demonstrado que Jagged1 regula positivamente a transcrição e activação de Notch4. Esta observação foi averiguada tanto no contexto angiogénico fisiológico como tumoral. Adicionalmente, a sinalização por Jagged1/Notch4 foi implicada na maturação vascular, uma vez que quer as feridas e tumores dos mutantes eJag1OE quer as feridas de ratinhos administrados com um anticorpo Notch4 agonista exibiram aumento da maturação vascular. Também foi demostrado que Jagged1 endotelial é capaz de activar Notch3/HeyL expresso nas células perivasculares e assim também contribuir para a regulação do recrutamento dessas mesmas células de suporte, tornando a vasculatura mais funcional e menos permeável, contribuindo para a cicatrização e desenvolvimento tumorais. Adicionalmente, foi demonstrado que o ligando endotelial Jagged1 contribui para a displasia tumoral não só pela sua função pró-angiogénica, limitando o aporte de nutrientes e oxigénio às células tumoriais, mas também por uma função angiócrina mediada pela activação de Notch3 e expressão de Hey1 nas células tumorais. Desta forma, este ligando regula ainda a proliferação, apoptose e diferenciação das células tumorais prostáticas, assim como o processo de transição epitélio-mesenquimal. Inclusivamente, através do estudo da expressão dos diferentes components Notch na próstata tumoral versus próstata normal, o eixo Jagged1/2/Notch3/Hey1 foi identificado como estando ectopicamente expresso no tecido prostático tumoral. Esta observação sugere então que para a regulação dos processos tumorigénicos referidos anteriormente, não só é importante o papel pró-angiogénico e angiócrino do ligando Jagged1 endotelial, mas também o seu papel directo decorrente da expressão aumentada ao nível das células tumorais. Por último, foi demonstrado que o bloqueio da sinalização Notch mediada pelos ligandos Jagged inibe o desenvolvimento e progressão de tumores da próstata do ratinho e que como tal, pode constituir uma nova potencial abordagem terapêutica no tratamento do cancro da próstata. O bloqueio de Jagged1/2 mimetizou o fenótipo vascular decorrente da perda-de-função endotelial específica de Jagged1, produzindo uma neo-vascularização menos densa, imatura e consequentemente menos funcional e mais permeável, inibindo fortemente o desenvolvimento de tumores da próstata murinos. De forma semelhante ao verificado nos mutantes de perda-de-função, o bloqueio de ambos os ligandos Jagged levou à inibição do crescimento celular próstático, restingindo a proliferação e promovendo a apoptose celular e inibindo a transição epitélio-mesenquimal. Adicionalmente, o tratamento com o anticorpo bloqueador também teve um efeito protector relativamente às alterações nos compartimentos celulares decorrentes da displasia prostática. O tratamento minimizou a perda da identidade celular luminal, inibiu a proliferação do compartimento basal e a des-diferenciação de um fenótipo luminal para um mais basal. O bloqueio de Jagged1/2 também apresentou um efeito benéfico ao nível da regulação do “pool” de células cancerosas estaminais da próstata, apresentado um efeito inibitório sobre a sua proliferação e sobrevivência. Adicionalmente, as amostras tratadas com anti-Jagged1/2 apresentaram uma significativa sub-expressão de Notch3 e Hey1 nesta subpopulação celular. Em conclusão, os resultados aqui apresentados contribuem para uma compreensão mais abrangente do papel do ligando Jaged1 no organismo adulto, fora do sistema nervoso central, inclusivamente em cenários tumorais, como o caso do cancro da próstata. De forma mais específica, a sinalização mediada por Jagged1, foi demonstrada ser uma rede complexa envolvendo múltiplos aspectos em diferentes tipos celulares e dependente do receptor envolvido. No endotélio Jagged1 actua como um ligando pró-angiogénico através de um efeito antagonístico a Dll4/Notch1 e mediado quer pela activação de Notch4/Hey1 no endotélio quer pela activação de Notch3/HeyL nas células perivasculares. Também foi importante verificar que ambas estas funções da sinalização por Jagged1/Notch são altamente conservadas em diferentes contextos no adulto, incluindo nos processos angiogénicos fisiológicos e patológicos. O ligando Jagged1 expresso por células endoteliais exerce ainda um papel angiócrino mediado pela activação de Notch3 e expressão de Hey1 na regulação do desenvolvimento tumoral da próstata. Esta função angiócrina juntamente com a expressão ectópica dos ligandos Jagged nos tecidos tumorais da próstata do ratinho constituem importantes fontes de regulação dos diversos aspectos da biologia tumoral. O bloqueio de Jagged1 pode desta forma vir a constituir um nova e promissora forma terapêutica no tratamento do cancro da próstata.
CIISA - Centro de Investigação Interdisciplinar em Sanidade Animal
PAZIENZA, VALERIO. "Impact of engineered food on tumor growth and chemoresistance in the frame of pancreatic cancer." Doctoral thesis, Università di Foggia, 2017. http://hdl.handle.net/11369/361941.
Повний текст джерелаThe impact of nutrition (particularly associated with short term starvation (STS)) on major health benefits have been already demonstrated. These include amelioration of cardiovascular diseases, diabetes, insulin resistance, immune disorders, slowing of the aging process and in particular reduced risks of cancer. Recent studies in rodent and in in vitro models uncovered a potential link between STS and improved efficacy of chemotherapy which has already been demonstrated for some types of cancer. The broader objective of the research project developed during the PhD program was to elucidate the role of fasting (or short term starvation, STS) on the intracellular signaling events involved in the chemo-resistance of pancreatic cancer (PC) amidst the most aggressive types of cancer ranked as the fourth leading cause of cancer-related deaths worldwide, in order to implement a new diet formulation, mimicking calories restriction, in order to reverse chemoresistance or inhibit tumor growth. Taking advantage of in vivo xenograft mouse model for pancreatic cancer and in vitro PC cell lines, using biochemical and biomolecular approaches we first aimed to understand in depth the role of STS during the onset of pancreatic cancer in an ad hoc murine model and we then elucidate the molecular mechanisms involved in PC chemoresistance. It is important to systematically identify potential targets, which could serve as biomarkers for cancer prevention, prognosis and treatment. By elucidating the mechanisms involved in PC chemoresistance the results of this study will help scientists to identify new therapeutic targets.
Karp, Cristina M. "HRPAP20 a novel tumor progression regulator in breast cancer /." Cincinnati, Ohio : University of Cincinnati, 2005. http://www.ohiolink.edu/etd/view.cgi?acc%5Fnum=ucin1108156644.
Повний текст джерелаHuijbers, Elisabeth J. M. "Development of a Cancer Vaccine Targeting Tumor Blood Vessels." Doctoral thesis, Uppsala universitet, Institutionen för medicinsk biokemi och mikrobiologi, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-170887.
Повний текст джерелаLi, Xingru. "Wilms' tumor gene 1 in different types of cancer." Doctoral thesis, Umeå universitet, Institutionen för medicinsk biovetenskap, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-103389.
Повний текст джерелаFemel, Julia. "Therapeutic Cancer Vaccines Targeting Molecules Associated with Tumor Angiogenesis." Doctoral thesis, Uppsala universitet, Institutionen för medicinsk biokemi och mikrobiologi, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-229572.
Повний текст джерелаMarabelle, Aurélien. "Targeting Tumor Specific Regulatory T-cells for Cancer Therapy." Thesis, Lyon, École normale supérieure, 2013. http://www.theses.fr/2013ENSL0832.
Повний текст джерелаActivation of TLR9 by direct injection of unmethylated CpG nucleotides into a tumor can induce a therapeutic immune response; however, regulatory T-cells (Tregs) eventually inhibit the antitumor immune response and thereby limit the power of cancer immunotherapies. In tumor-bearing mice, we found that Tregs within the tumor preferentially express the cell surface markers CTLA-4 and OX40. We show that intratumoral coinjection of anti–CTLA-4 and anti-OX40 together with CpG depleted tumor-infiltrating Tregs. This in situ immunomodulation, which was performed with low doses of antibodies in a single tumor, generated a systemic antitumor immune response that eradicated disseminated disease in mice. Further, this treatment modality was effective against established CNS lymphoma with leptomeningeal metastases, sites that are usually considered to be tumor cell sanctuaries in the context of conventional systemic therapy. These results demonstrate that antitumor immune effectors elicited by local immunomodulation can eradicate tumor cells at distant sites. We propose that, rather than using mAbs to target cancer cells systemically, mAbs could be used to target the tumor infiltrative immune cells locally, thereby eliciting a systemic immune response
Derniame, Sophie. "Cancer du poumon / Réponse immunitaire locale - modulation tumeur dépendante." Nancy 1, 2006. http://docnum.univ-lorraine.fr/public/SCD_T_2006_0097_DERNIAME.pdf.
Повний текст джерелаLung cancer is the most frequent type of cancer in the world. Smoking is clearly the major cause of this pathology. The proliferation of tumor cells induces an inflammatory stromal reaction comprising numerous tumor-infiltrating lymphocytes. In this study, four complementary approaches have been used to study the tumor-dependent modulation of the immune system : TCR Vβ repertoire usage in flow cytometry, TCRγ gene clonal rearrangements in denaturing gradient gel electrophoresis (DGGE/TTGE), tumor and healthy lung tissue infiltration as well as lymph nodes characteristics in immunohistology and cytokine production by RNA RT-PCR. The results obtained have demonstrated the oligoclonality of T-cells in the three types of tissues tested. A Vβ13. 1 clone and a gamma clone appeared to be specifics of epidermoid carcinoma. Similarly, two TCRγ clones appeared to be restricted to adenocarcinoma. Moreover, the CD3/TCR complex was clearly down regulated in tumors compared to healthy tissue or lymph nodes. Similarly, HLA-DR, HLA-DQ and β2 microglobuline, strongly expressed on healthy pneumocytes were nearly absent from tumor cells. Several cytokines with antagonistic effects were detected within tumoral tissue, especially TGFβ and IL-10, which favour tumor growth and TNFalpha and IFNγ which potentialize the anti-tumoral immune response. In conclusion, the clones identified in healthy lung tissue could be specific of early pre-tumoral lesions induced by tobacco smoke, and some of the clones appear to be tumor-specific. However, the immune system has been defeated by several mechanisms, including a decrease of the expression of partners of the immunological synapse and the production of antagonistic cytokines
Cruz, Giovanna Ibeth. "Pregnancy and its association with breast cancer tumor subtypes." Thesis, The University of Arizona, 2011. http://hdl.handle.net/10150/144593.
Повний текст джерела