To see the other types of publications on this topic, follow the link: Tumor Formation.
Dissertations / Theses on the topic 'Tumor Formation'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 dissertations / theses for your research on the topic 'Tumor Formation.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse dissertations / theses on a wide variety of disciplines and organise your bibliography correctly.
1
Liu, Dan. "The role of senescent fibroblasts in tumor formation : a dissertation /." San Antonio : UTHSC, 2006. http://proquest.umi.com/pqdweb?did=1257790121&sid=1&Fmt=2&clientId=70986&RQT=309&VName=PQD.
Full text
2
Rangwala, Fatima. "Ras signalling in Schwann cell tumor formation neurofibromatosis type 1 /." Cincinnati, Ohio : University of Cincinnati, 2003. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=ucin1069774794.
Full text
3
Ortiz, Myrna Lillian. "Immature Myeloid Cells Promote Tumor Formation Via Non-Suppressive Mechanism." Scholar Commons, 2014. https://scholarcommons.usf.edu/etd/5089.
Full textAbstract:
ABSTRACT
Although there is ample evidence linking chronic inflammation with cancer, the cellular mechanisms involved in early events leading to tumor development remain unclear. Myeloid cells are an intricate part of inflammation. They consist of mature cells represented by macrophages, dendritic cells and granulocytes and a population of Immature Myeloid Cells (IMC), which in healthy individuals are cells in transition to mature cells. There is a substantial expansion of IMC in cancer and many other pathological conditions which is associated with pathologic activation of these cells. As a result, these cells acquire the ability to suppress immune responses and are termed Myeloid-derived Suppressor Cells (MDSCs). Although the role of MDSC in immune suppression in cancer and tumor progression is well established, their contribution to tumor development is still uncertain. The fact that cells with MDSC phenotype and function are observed in chronic inflammation raised the possibility that these cells can contribute to initial stages of tumor development. To address this question, we used an experimental system where the number of IMC was regulated by the expression of S100A9 protein.
In this project, we used two different models of chronic inflammation in S100A9 transgenic (S100A9tg) and S100A9 knock-out (S100A9KO) mice. In the first model, we created the conditions for topical accumulation of these cells in the skin in the absence of infection or tissue damage using S100A9tg mice. Accumulation of IMC in the skin resulted in a dramatic increase in the formation of skin tumors during epidermal carcinogenesis. Conversely, lack of myeloid cell accumulation in S100A9KO mice substantially reduced the formation of skin papillomas. The effect of IMC was not associated with immune suppression but with the recruitment of CD4+ T cells mediated by CCL4 chemokine released by activated IMC. Elimination of CD4+ T cells or blockade of CCL4 abrogated the increase in tumor formation caused by myeloid cells. Thus, this study implicates the accumulation of IMC as an initial step in facilitating of tumor formation, which can mediate the recruitment of CD4+ T cells via the release of CCL4 chemokine.
In the second model, we used inflammation-associated lung cancer caused by the chemical lung carcinogen urethane in combination with exposure to cigarette smoke referred to throughout as CS. Exposure of mice to CS alone resulted in a significant accumulation of cells with typical MDSC phenotype in different organs; however, these cells lacked immune suppressive activity and could not be defined as bona fide MDSC. When CS was combined with the single dose of urethane, it led to the accumulation of immune suppressive cells. The expansion of MDSC followed the onset of lung tumors development. This suggests that MDSC in this model is not the preceding factor but rather a consequence of tumor formation. Further studies are necessary to determine the relevance of targeting these cells for cancer treatment and prevention.
4
RANGWALA, FATIMA ABDULLA. "RAS SIGNALING IN SCHWANN CELL TUMOR FORMATION: NEUROFIBROMATOSIS TYPE 1." University of Cincinnati / OhioLINK, 2003. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1069774794.
Full text
5
Saelzler, Matthew P. (Matthew Paul). "The recruitment of stromal cells to the site of tumor formation." Thesis, Massachusetts Institute of Technology, 2009. http://hdl.handle.net/1721.1/57520.
Full textAbstract:
Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, February 2010.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
Cataloged from student submitted PDF version of thesis. Vita.
Includes bibliographical references.
Myofibroblasts are an alpha-smooth muscle actin ([alpha]-SMA)-expressing cell type found within human mammary carcinomas, but not in the normal mammary gland. Myofibroblasts can enhance tumor formation by promoting angiogenesis and invasion, and we therefore sought to better understand how myofibroblasts are incorporated into breast carcinomas. By identifying secreted factors that recruit myofibroblasts as well as the physical niche where they originated, we aimed to identify possible therapeutic targets to inhibit their incorporation. Using a newly developed mammary carcinoma model, termed BPLER, we identified CXCL1, VEGF, CCL5, and IL-6 as factors that may be important for the recruitment of myofibroblasts. We tested the ability of CXCL1, VEGF164, or CCL5 to affect tumor formation and induce the incorporation of a-SMApositive cells. We show that the expression in MCF-7-Ras modified human breast cancer cells of VEGF164, but not CXCL1 or CCL5, results in the promotion of primary tumor growth and the increased incorporation of [alpha]-SMA-positive cells. Furthermore, we demonstrate that these a-SMA-positive cells do not correlate with cells expressing CD34, a marker of endothelial cells, suggesting that these cells are not [alpha]-SMA-positive smooth muscle cells. Thus, we propose that VEGF is a critical factor that recruits myofibroblasts to the site of breast cancer formation. In another line of experiments, we examined the source of the [alpha]-SMA-positive cell population recruited to another mammary tumor model, termed BPHER-3.
(cont.) In order to investigate whether these cells are derived from the bone marrow, we utilized chimeric mice that express green fluorescent protein (GFP) in their bone marrow and blood cells in order to look for incorporation of GFP-labeled cells within the stroma of a subcutaneously grown tumor. We demonstrated that green bone marrow-derived cells are robustly recruited to the site of BPHER-3 tumor formation; however strikingly, almost 100% of the [alpha]-SMA positive cells analyzed were GFP negative. Our results demonstrate that the [alpha]-SMA-positive cell population recruited to BPHER-3 tumors is not bone marrow-derived, but is instead recruited from the adjacent tissue microenvironment.
by Matthew P. Saelzler.
Ph.D.
6
Appleman, Victoria A. "Mechanisms of KRAS-Mediated Pancreatic Tumor Formation and Progression: A Dissertation." eScholarship@UMMS, 2012. https://escholarship.umassmed.edu/gsbs_diss/600.
Full textAbstract:
Pancreatic cancer is the 4th leading cause of cancer related death in the United States with a median survival time of less than 6 months. Pancreatic ductal adenocarcinoma (PDAC) accounts for greater than 85% of all pancreatic cancers, and is marked by early and frequent mutation of the KRAS oncogene, with activating KRAS mutations present in over 90% of PDAC. To date, though, targeting activated KRAS for cancer treatment has been very difficult, and targeted therapies are currently being sought for the downstream effectors of activated KRAS. Activation of KRAS stimulates multiple signaling pathways, including the MEK-ERK and PI3K-AKT signaling cascades, but the role of downstream effectors in pancreatic tumor initiation and progression remains unclear. I therefore used primary pancreatic ductal epithelial cells (PDECs), the putative cell of origin for PDAC, to determine the role of specific downstream signaling pathways in KRAS activated pancreatic tumor initiation. As one third of KRAS wild type PDACs harbor activating mutations in BRAF , and KRAS and BRAF mutations appear to be mutually exclusive, I also sought to determine the effect of activated BRAF (BRAF V600E ) expression on PDECs and the signaling requirements downstream of BRAF.
I found that both KRAS G12D and BRAF V600E expressing PDECs displayed increased proliferation relative to GFP expressing controls, as well as increased PDEC survival after challenge with apoptotic stimuli. This survival was found to depend on both the MEK-ERK and PI3K-AKT signaling cascades. Surprisingly, I found that this survival is also dependent on the IGF1R, and that activation of PI3K/AKT signaling occurs downstream of MEK/ERK activation, and is dependent on signaling through the IGF1R. Consistent with this, I find increased IGF2 expression in KRAS G12D and BRAF V600E expressing PDECs, and show that ectopic expression of IGF2 rescues survival in PDECs with inhibited MEK, but not PI3K. Finally, I showed that the expression of KRAS G12D or BRAF V600E in PDECs lacking both the Ink4a/Arf and Trp53 tumor suppressors is sufficient for tumor formation following orthotopic transplant of PDECs, and that IGF1R knockdown impairs KRAS and BRAF-induced tumor formation in this model.
In addition to these findings within PDECs, I demonstrate that KRAS G12D or BRAF V600E expressing tumor cell lines differ in MEK-ERK and PI3K-AKT signaling from PDECs. In contrast to KRAS G12D or BRAF V600E expressing PDECs, activation of AKT at serine 473 in the KRAS G12D or BRAF V600E expressing tumor cell lines does not lie downstream of MEK, and only the inhibition of PI3K alone or both MEK and the IGF1R simultaneously results in loss of tumor cell line survival. However, inhibition of MEK, PI3K, or the IGF1R in KRAS G12D or BRAF V600E expressing tumor cell lines also resulted in decreased proliferation relative to DMSO treated cells, demonstrating that all three signaling cascades remain important for tumor cell growth and are therefore viable options for pancreatic cancer therapeutics.
7
Lähdesmäki, Aleksi. "Functional analysis of ATM with relevance for primary immunodeficiency and tumor formation /." Stockholm, 2004. http://diss.kib.ki.se/2004/91-7349-900-5/.
Full text
8
Ueo, Taro. "The role of Hes genes in intestinal development, homeostasis and tumor formation." Kyoto University, 2012. http://hdl.handle.net/2433/158055.
Full text
9
Branschädel, Marcus. "Analysis of molecular components essential for the formation of signaling competent TNF-TNFR complexes." [S.l. : s.n.], 2007. http://nbn-resolving.de/urn:nbn:de:bsz:93-opus-32358.
Full text
10
Persa, Oana-Diana [Verfasser]. "The role of aPKC polarity in migration and tumor formation / Oana-Diana Persa." Köln : Deutsche Zentralbibliothek für Medizin, 2014. http://d-nb.info/1061094715/34.
Full text
11
Buckwalter, Tara Lynne Furminger. "Phosphotyrosine-mediated signal transduction pathways essential for RET/PTC-1-induced tumor formation /." The Ohio State University, 2000. http://rave.ohiolink.edu/etdc/view?acc_num=osu970163275.
Full text
12
Rodriguez, Alejandro. "Studies of Stroma Formation and Regulation in Human Pathological Conditions and in Experimental in vivo Models." Doctoral thesis, Uppsala universitet, Institutionen för medicinsk biokemi och mikrobiologi, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-120688.
Full textAbstract:
Fibrosis is a sequel of chronic inflammation and is defined as an excessive deposition of collagen that ultimately leads to organ dysfunction. To date there are no effective treatments for fibrosis. The main cell type involved in collagen deposition and organization is the myofibroblast. In the first study we examined how myofibroblasts differentiate in human fibrotic conditions and in experimental animal models. Human tissues were stained with antibodies that recognize integrin receptors and in addition we also stained for α-SMA, a myofibroblast marker. We found a co-localization between these two markers in stromal cells and hypothesized that integrin α1 is important for the acquisition of the myofibroblast phenotype. To tests this hypothesis we used knockout animals for this integrin subunit. These animals showed a reduction of α-SMA positive fibroblasts, indicating that the α1 integrin subunit is required for proper myofibroblast differentiation. In the second study we used a neuroblastoma tumor model to study tumour growth when a drug targeting the synthesis of cellular NAD was administered. In treated animals an expansion of the nonvascular stroma was observed compared to controls. Normalization of the vasculature was observed in treated tumors together with a decrease in hypoxia. Moreover, this was followed by a decrease in stromal PDGF-B and VEGF expression, suggesting a deactivation of the stroma. In the third study the effects of over-expression of the two pro-fibrotic growth factors TGF-β and PDGF-B in skin was evaluated. We observed that both growth factors induced fibrosis. Over time, a decrease in blood vessel density was observed in both treatment groups. Both factors also stimulated an expansion of the connective tissue cell population originating from the microvascular pericyte, but the phenotype of these cells differed in the different treatments with regards to expression of markers. Furthermore, in tissue over-expressing PDGF-B but not TGF-β, the fibrotic process was partially reversible.
13
Mazumdar, Tapati. "ROLE AND REGULATION OF MYC IN GLIOBLASTOMA MULTIFORME CELL DIFFERENTIATION: IMPLICATION IN TUMOR FORMATION." [Kent, Ohio] : Kent State University, 2008. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=kent1214366273.
Full textAbstract:
Thesis (Ph.D.)--Kent State University, 2008.Title from PDF t.p. (viewed Sept. 28, 2009). Advisor: Saikh Jaharul Haque. Keywords: GBM; Differentiation; Myc; Stat3; GFAP. Includes bibliographical references (p. 153-189).
14
Fukuda, Hitoshi. "FACS-based purification of ES cell-derived neural precursors averts tumor formation after transplantation." Kyoto University, 2006. http://hdl.handle.net/2433/143815.
Full textAbstract:
Kyoto University (京都大学)0048
新制・課程博士
博士(医学)
甲第12182号
医博第2935号
新制||医||914(附属図書館)
24018
UT51-2006-J175
京都大学大学院医学研究科脳統御医科学系専攻
(主査)教授 中畑 龍俊, 教授 山中 伸弥, 教授 中辻 憲夫
学位規則第4条第1項該当
15
Atieh, 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.
Full textAbstract:
Les carcinomes sont des cancers touchant plusieurs organes du corps humain, notamment les seins, le pancréas, les poumons, l'intestin… et sont issus de la transformation de cellules épithéliales en cellules tumorales. Au cours du développement d'une tumeur, les cellules cancéreuses, contrairement aux cellules normales, acquièrent la capacité de se déplacer dans le corps humain, jusqu'à coloniser des organes voisins. Ces colonies sont appelées métastases. Le processus métastatique est responsable de 90% des décès dans le cadre des carcinomes. Ce processus n'est pas dû à l'action isolée des cellules cancéreuses mais est aussi le résultat d'une coopération entre la tumeur et son voisinage – le microenvironnement tumoral – favorisant la survie et la migration des cellules cancéreuses. Les fibroblastes sont une population cellulaire du microenvironnement tumoral. Il a été démontré que les fibroblastes sont activés à proximité des cellules cancéreuses ; on les qualifie de fibroblastes associés au cancer ou CAFs. Dans des tissus de patients, les tumeurs les plus agressives corrèlent avec un enrichissement en fibroblastes et une matrice plus dense. Mon projet de thèse illustre un nouveau mécanisme de coopération entre CAFs et cellules cancéreuses. Cibler l’action des fibroblastes pourrait ralentir la progression tumorale, voire bloquer la formation de métastasesCancer-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
16
Vázquez, Ferrer Eric 1990. "The Role of adult stem cells in tumor formation : mutations in Sox2+ cells induce lineage-specific proliferation." Doctoral thesis, Universitat Pompeu Fabra, 2017. http://hdl.handle.net/10803/664240.
Full textAbstract:
It has been well-established that progressive accumulation of genetic mutations in proto-oncogenes and tumor suppressors induces cancer. However, the early molecular mechanisms leading to tumor initiation remain elusive. Recent studies have shown that there are tissue- and cell-type-specific vulnerabilities to oncogenic stimuli. Mutations in adult stem/progenitor cells (ASCs/PCs) have been suggested to underlie the formation of tumor initiating cell populations. Here, we sought to identify proliferative ASCs/PCs that are the most susceptible to oncogenic mutations. Expression of different oncogenic stimuli (oncogenic KrasG12D, knockout of p53, overexpression of Myc) in Sox2-positive ASCs, led to a hyperplasic phenotype. Interestingly, this was confined to the stomach and esophagus, despite there being Sox2+ cells in many other organs. These observations point to Sox2+ foregut epithelial cells as the most vulnerable to oncogenic insults. Our observations also revealed distinct roles for each of the oncogenic stimuli in cancer progression. Kras expression, but not p53 deletion, suffices for tumor formation while p53 is involved in the acquisition of an invasive potential. Finally, Myc activation not only induced hyperplasia in the esophagus and forestomach, but also drove metastatic transplantable adenocarcinomas in the glandular stomach, suggesting that Sox2+ cells could be the Cancer Cells of Origin (CCOs) for gastric cancer. Together, our results may open new paths for a better understanding of tumor initiation and promotion.És ben sabut que l’acumulació progressiva de mutacions genètiques en proto-oncogens i en gens supressors de tumors indueix càncer. Ara bé, els mecanismes moleculars que condueixen a la iniciació dels tumors són encara incerts. Estudis recents mostren que hi ha vulnerabilitats específiques cel·lulars i de teixits quant als estímuls oncogènics. Mutacions en cèl·lules mare adultes o en cèl·lules progenitores s’han proposat com a mecanismes de formació de cèl·lules tumorals iniciadores de tumors. En aquest estudi, hem volgut identificar cèl·lules mare adultes o cèl·lules progenitores que són més susceptibles a mutacions oncogèniques. L’expressió de diferents estímuls oncogènics (l’oncogen KrasG12D, l’eliminació de p53, la sobreexpressió de Myc) en cèl·lules mare adultes Sox2 positives promou un fenotip hiperplàsic. Aquest fenomen només l’observem en l’estómac i en l’esòfag, tot i havent cèl·lules mare adultes Sox2 positives en molts altres òrgans. Aquestes observacions senyalen que les cèl·lules més vulnerables als estímuls oncogènics són les cèl·lules epitelials del tracte digestiu més superior. A més, també observem rols diferents per cadascun dels estímuls oncogènics en la progressió del càncer. L’oncogen KrasG12D, però no l’eliminació de p53, és suficient per a la iniciació del tumor, mentre que p53 es troba involucrat en la invasió. També, la sobreexpressió de Myc no només indueix hiperplàsia en l’estómac i en l’esòfag sinó que també forma en l’estómac glandular adenocarcinomes metastàtics amb capacitat de transplantament, suggerint que les cèl·lules Sox2 positives podrien ésser les cèl·lules iniciadores de tumors en els càncers gàstrics. En resum, els nostres resultats obren noves vies per a una millor comprensió de la iniciació i progressió dels tumors.
17
Østevold, Kristine [Verfasser], and Klaus [Akademischer Betreuer] Aktories. "Septin remodeling is essential for the formation of cell membrane protrusions (microtentacles) in detached tumor cells." Freiburg : Universität, 2018. http://d-nb.info/1163533785/34.
Full text
18
Anderson, Ericka L. (Ericka Lynne). "The Role of Stra8 in spermatogenesis : regulation of spermatogonial differentiation, meiotic initiation, and testicular tumor formation." Thesis, Massachusetts Institute of Technology, 2010. http://hdl.handle.net/1721.1/65168.
Full textAbstract:
Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2011.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
Cataloged from student submitted PDF version of thesis.
Includes bibliographical references (p. 124-129).
Spermatogenesis is a highly regulated, cyclical process where sperm are constantly produced. Previous work characterizing male rodents maintained on a Vitamin A Deficient diet has demonstrated that retinoic acid (RA) governs two transitions during mammalian spermatogenesis. These germ cell transitions include the transition from undifferentiated spermatogonia to differentiating spermatogonia, which continue to proliferate mitotically, and the transition from mitosis to meiosis. This work led to questions about the mechanisms through which RA governs these transitions. Here I will present my findings demonstrating that Stra8, previously demonstrated to be a RA-induced gene, is a target gene of RA in both the transition from undifferentiated spermatogonia to differentiating spermatogonia and the transition from mitosis to meiosis. I conclude that RA inducing Stra8 is the mechanism that regulates these developmental transitions. The architecture of germ cell development in the rodent testis is such that these two RA-governed transitions occur in immediate physical proximity, suggesting the possibility that the RA inducing Stra8 mechanism could regulate both transitions simultaneously. I conclude that this mechanism could play a part in the regulation of the seminiferous cycle during spermatogenesis. In the appendices I will also present my findings that demonstrate Stra8 functions in testicular germ cell tumors. I conclude that Stra8 function in the transition from undifferentiated spermatogonia to differentiating spermatogonia acts as a tumor suppressor for seminoma tumors. In contrast, I find that Stra8 is required for testicular teratomas to form, indicating a role for Stra8 in the formation of these tumors.
by Ericka L. Anderson.
Ph.D.
19
Alfardan, Rana. "ROLES OF 15-LIPOXYGENASE-2 (ALOX15B) IN SUPPRESSION OF TUMOR FORMATION, METASTASIS, AND SENSITIVITY TO CHEMOTHERAPY." OpenSIUC, 2018. https://opensiuc.lib.siu.edu/dissertations/1545.
Full textAbstract:
15-LOX-2 is a member of the lipoxygenase family with anti-tumorigenic activity. Like other lipoxygenase families, the main substrate for 15-LOX-2 in the Arachidonic acid. The main product of this enzyme is 15(S)-HETE. 15(S)-HETE control the proliferation in prostate cells. The expression of 15-LOX-2 lost in the metastatic stage of prostate tumor compared to the primary and benign tumor. To investigate the role of 15-LOX-2 in a highly metastatic prostate tumor, we overexpressed 15-LOX-2 in PC3MM cell line using Lenti-X Tet-on advanced inducible expression system. Exposure to 75ng/ml of doxycycline for 24h produced prompt 15-LOX-2 at the protein level. In addition, removing the inducible molecule for 72h halted the 15-LOX-2 expression. After induction of 15-LOX-2 for 96h, the cells started to have more epithelial-like phenotypes compared to the untreated or vector control cells. The cells with 15-LOX-2 induction have a bigger and flattened shape with less cytoplasmic extension compared to the untreated and vector control cells. Overexpression of 15-LOX-2 led to reverse the epithelial to mesenchymal process. 15-LOX-2 overexpression led to increasing the expression of junctional complex structural proteins. However, 15-LOX-2 overexpression led to decrease the expression of the mesenchymal markers and matrix metalloproteases. In addition, we proved the ability of 15-LOX-2 to inhibit the tumor growth in vivo and increase the chemotherapy sensitivity in vitro. To investigate the biological role of 15-LOX-2 in vivo, we used mice with a deletion in the ALOX8 (15-LOX-2 orthologue in mice). Mice with a deletion in ALOX8 showed increased in the formation of mass like a tumor in the lung, and chronic inflammation compared to the wildtype. In addition, the infection of these mice with X31 virus indicated an important role for ALOX8 in the recovery process after infection with influenza virus.
20
Sperlazza, Justin. "Depletion of the Chromatin Remodeler CHD4 Sensitizes AML Blasts to Genotoxic Agents and Reduces Tumor Formation." VCU Scholars Compass, 2015. http://scholarscompass.vcu.edu/etd/4005.
Full textAbstract:
Chromodomain Helicase DNA-Binding Protein 4 (CHD4) is an ATPase that alters the phasing of nucleosomes on DNA and has recently been implicated in DNA double stranded break (DSB) repair. Here, we show that depletion of CHD4 in Acute Myeloid Leukemia (AML) blasts induces a global relaxation of chromatin that renders cells more susceptible to DSB formation, while concurrently impeding their repair. Furthermore, CHD4 depletion renders AML blasts more sensitive both in vitro and in vivo to genotoxic agents used in clinical therapy: daunorubicin (DNR) and cytarabine (ara-C). Sensitization to DNR and ara-C is mediated in part by activation of the ATM pathway, which is preliminarily activated by a Tip60-dependent mechanism in response to chromatin relaxation and further activated by genotoxic-agent induced DSBs. This sensitization preferentially affects AML cells, as CHD4 depletion in normal CD34+ hematopoetic progenitors does not increase their susceptibility to DNR or ara-C. Unexpectedly, we found that CHD4 is necessary for maintaining the tumor formatting behavior of AML cells, as CHD4 depletion severely restricted the ability of AML cells to form xenografts in mice and colonies in soft agar. Taken together, these results provide evidence for CHD4 as a novel therapeutic target whose inhibition has the potential to enhance the effectiveness of genotoxic agents used in AML therapy.
21
Shaik, Anjumara [Verfasser]. "Partial frataxin suppression in Caenorhabditis elegans reduces tumor formation by dampening the RAS/MAPk signaling / Anjumara Shaik." Düsseldorf : Universitäts- und Landesbibliothek der Heinrich-Heine-Universität Düsseldorf, 2017. http://d-nb.info/1129357252/34.
Full text
22
Cheng, Zhen. "Rhenium cyclized [alpha]-MSH analogs, somatostatin analogs and T-antigen avid peptides as imaging and therapeutic agents for tumor targeting /." free to MU campus, to others for purchase, 2001. http://wwwlib.umi.com/cr/mo/fullcit?p3012959.
Full text
23
Tang, Nan. "The essential roles of HIF-1[alpha] and VHL in endothelial cells during development and solid tumor formation /." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2005. http://wwwlib.umi.com/cr/ucsd/fullcit?p3190167.
Full text
24
Sun, Huayan. "Function of the β4 Integrin in Cancer Stem Cells and Tumor Formation in Breast Cancer: A Masters Thesis." eScholarship@UMMS, 2001. http://escholarship.umassmed.edu/gsbs_diss/814.
Full textAbstract:
The integrin α6β4 (referred to as β4) is expressed in epithelial cells where it functions as a laminin receptor. Integrin β4 is important for the organization and maintenance of epithelial architecture in normal cells. Particularly, β4 is shown to be essential for mammary gland development during embryogenesis. Integrin β4 also plays important roles in tumor formation, invasion and metastasis in breast cancer. However, the mechanism of how integrin β4 mediates breast tumor formation has not been settled. A few studies suggest that integrin β4 is involved in cancer stem cells (CSCs), but the mechanism is not clear. To address this problem, I examined the expression of β4 in breast tumors and its potential role involved in regulating CSCs. My data shows that β4 is expressed heterogeneously in breast cancer, and it is not directly expressed in CSCs but associated with a basal epithelial population. This work suggests that β4 can regulate CSCs in a non-cell-autonomous manner through the interactions between β4+ non-CSC population and β4- CSC population. My data also shows that β4 expression is associated with CD24+CD44+ population in breast tumor. To further study the role of β4 in breast cancer progression, I generated a β4 reporter mouse by inserting a p2A-mCherry cassette before ITGB4 stop codon. This reporter mouse can be crossed with breast tumor models to track β4+ population during tumor progression.
25
Sun, Huayan. "Function of the β4 Integrin in Cancer Stem Cells and Tumor Formation in Breast Cancer: A Masters Thesis." eScholarship@UMMS, 2016. https://escholarship.umassmed.edu/gsbs_diss/814.
Full textAbstract:
The integrin α6β4 (referred to as β4) is expressed in epithelial cells where it functions as a laminin receptor. Integrin β4 is important for the organization and maintenance of epithelial architecture in normal cells. Particularly, β4 is shown to be essential for mammary gland development during embryogenesis. Integrin β4 also plays important roles in tumor formation, invasion and metastasis in breast cancer. However, the mechanism of how integrin β4 mediates breast tumor formation has not been settled. A few studies suggest that integrin β4 is involved in cancer stem cells (CSCs), but the mechanism is not clear. To address this problem, I examined the expression of β4 in breast tumors and its potential role involved in regulating CSCs. My data shows that β4 is expressed heterogeneously in breast cancer, and it is not directly expressed in CSCs but associated with a basal epithelial population. This work suggests that β4 can regulate CSCs in a non-cell-autonomous manner through the interactions between β4+ non-CSC population and β4- CSC population. My data also shows that β4 expression is associated with CD24+CD44+ population in breast tumor. To further study the role of β4 in breast cancer progression, I generated a β4 reporter mouse by inserting a p2A-mCherry cassette before ITGB4 stop codon. This reporter mouse can be crossed with breast tumor models to track β4+ population during tumor progression.
26
Kheimar, Ahmed Mahmoud Osman [Verfasser]. "Tumor promoting functions of cellular telomerase RNA and viral RNAs in herpesvirus-induced cancer formation / Ahmed Mahmoud Osman Kheimar." Berlin : Freie Universität Berlin, 2017. http://d-nb.info/1147758247/34.
Full text
27
Biyajima, Kyoko. "Matrix metalloproteinase 7 is required for tumor formation, but dispensable for invasion and fibrosis in SMAD4-deficient intestinal adenocarcinomas." Kyoto University, 2009. http://hdl.handle.net/2433/124281.
Full text
28
Esmailzadeh, Sharmin. "The role of BIN1 in the regulation of cell proliferation, apoptosis and tumor formation in cutaneous T-cell lymphoma." Thesis, University of British Columbia, 2014. http://hdl.handle.net/2429/50568.
Full textAbstract:
Cutaneous T-cell lymphomas (CTCLs) represent a group of lymphoproliferative disorders characterized by homing of malignant T-cells to the skin’s surface. There are two main types of CTCL: Mycosis Fungoides (MF) and Sezary Syndrome (SS). We have demonstrated that expression of the Abelson helper integration site-1 (AHI-1) oncogene is significantly increased in CD4⁺CD7- cells from SS patients. Bridging integrator 1 (BIN1) has been identified by microarray analysis of CTCL cells as a candidate gene involved in AHI-1-mediated lymphomagenesis. Interestingly, BIN1expression is significantly reduced in SS patient samples. However, the role of BIN1 and its molecular connection to AHI-1 in lymphomagenesis remains unexplored.
I extensively investigated the role of key BIN1 isoforms in primary and CTCL cell line model systems both in vitro and in vivo. I demonstrated that overexpression/restored expression of BIN1 isoforms has strong anti-proliferative and pro-apoptotic roles in CTCL cells in vitro, and significantly inhibits the tumorigenic activity of these cells in vivo. The pro-apoptotic role of BIN1 in CTCL cells occurs through downregulation of c-FLIP, a critical inhibitor of Fas/FasL-mediated apoptosis. I also observed significant reduction and increase in BIN1 and c-FLIP transcripts in primary CTCL samples, respectively. Interestingly, high BIN1 and low c-FLIP transcripts correlated with better survival rate in SS patients. Thus, BIN1 deficiency may play an important role in CTCL pathogenesis by causing apoptosis resistance.
Furthermore, I explored potential mechanisms by which AHI-1 leads to downregulation of BIN1, by (1) examining if AHI-1 physically interacts with BIN1; and (2) determining if AHI-1 alters transcription of BIN1 by changing the methylation status of the BIN1 promoter. These experiments did not yield direct evidence of these two potential mechanisms of AHI-1’s role in BIN1 suppression. Thus, the mechanism by which AHI-1 regulates BIN1 remains unknown. Nevertheless, several potential BIN1 interacting proteins were uncovered in CTCL cells, including α/β-tubulin and β-actin.
Overall, this study provides the first evidence of strong tumor suppressor activity of BIN1 in CTCL. It points to the loss of BIN1 and subsequent upregulation of c-FLIP as an important mechanism to induce apoptosis resistance in CTCL cells, and identifies BIN1 and c-FLIP as potential CTCL therapeutic targets.Medicine, Faculty of
Medical Genetics, Department of
Graduate
29
Plantureux, Léa. "Conséquences de l'interaction des plaquettes avec les cellules cancéreuses sur le développement de la tumeur et la formation de métastases : cas du cancer colorectal." Thesis, Aix-Marseille, 2018. http://www.theses.fr/2018AIXM0691.
Full textAbstract:
Les plaquettes participent activement à la formation de métastases. Cependant, leurs rôles dans la croissance tumorale sont controversés. Dans cette étude, nous avons décidé d’étudier les interactions des plaquettes avec des tumeurs colorectales. Nous avons démontré que les plaquettes s’extravasent dans le microenvironnement et interagissent avec les cellules tumorales via la cadhérine-6. Cette interaction induit la génération de trois types de microparticules, nommée iMPs, exprimant des marqueurs plaquettaires, tumoraux ou les deux et sont retrouvées dans le plasma et dans les tumeurs primaires de patients souffrant d’un cancer colorectal. Dans le microenvironnement tumoral, les plaquettes induisent une diminution de la croissance tumorale et une augmentation du nombre de macrophages intra-tumoraux. Les iMPs participent au recrutement des macrophages dans le microenvironnement et activent leur capacités anti-tumorales à travers les cytokines IFN-g et Il-4. Ce mécanisme mène à l’arrêt du cycle cellulaire via l’induction de la protéine P21. En revanche, dans la circulation, les plaquettes et la production des iMPs augmentent l’adhésion des cellules tumorales à l’endothélium principalement par le transfert de l’intégrine ß3 aux cellules tumorales et via l’activation des cellules endothéliales. Dans le microenvironnement tumoral, les interactions cadhérine-6 dépendantes entre les plaquettes et les cellules tumorales induisent la génération de iMPs menant au recrutement et à l’activation des macrophages tumoricides, alors que dans la circulation, les plaquettes et les iMPs favorisent l’adhésion des cellules tumorales à l’endothélium, promouvant la formation de métastasesIncreasing evidence has demonstrated that platelets actively participate to the progression of metastasis. However, their roles in tumor growth are still subject to controversy. Here, we investigated the interaction of platelets with colorectal tumors. We showed that platelets extravasate in the tumor microenvironment and interact with the tumor cells in a cadherin-6 dependent manner. This interaction induces the spreading of platelets, the release of their granules content and the generation of three types of microparticles named iMPs expressing makers of platelets, tumor and both. The presence of iMPs was confirmed in patients suffering from a colorectal cancer. In the microenvironment, platelets induce a significant diminution of the tumor growth and a significant increase in the number of intratumoral macrophages. iMPs participate in the recruitment of macrophages by vectorizing the cytokines RANTES, CCL2 and CXCL12 and activate their tumor cell killing capacity through IFN-gamma and IL-4. This lead to the cell cycle arrest of the tumor in a P21 dependent pathway. In contrast, in the bloodstream, platelets and production of iMPs induce the adhesion of tumor cells to the endothelium mainly via the transfer of ß3 integrin from platelets to tumor and the activation of endothelial cells. Altogether, our results indicate that, in the tumor microenvironment, Cadherin- 6 dependent platelet-tumor cells interactions induce the generation of iMPs leading to the recruitment and the activation of tumoricidal macrophages whereas, in bloodstream, platelets and circulating iMPs favor the interaction of tumor cells with the endothelium, promoting the formation of metastasis
30
Enck, Robert E., Fadi Abushahin, and John B. Bossaer. "Soft Tissue Calcification Secondary to Imatinib Mesylate in a Patient with Gastrointestinal Stromal Tumor." Digital Commons @ East Tennessee State University, 2013. https://dc.etsu.edu/etsu-works/2321.
Full textAbstract:
Imatinib mesylate has been associated with the changes in bone turnover. We report a case of the development of tissue calcification in a patient on long-term therapy with this drug. A 48-year-old male patient with gastrointestinal stromal tumor and liver metastasis complained of abdominal pain. His treatment included hepatic artery chemoembolization and partial hepatectomy in addition to chronic imatinib mesylate for 4 years. On physical examination, he had a peritoneal mass just beneath the laparotomy incision scar that, after resection, was found to be dystrophic bone formation. Based on the previous studies suggesting bone changes due to chronic therapy with imatinib mesylate, we believe that the patient's new bone formation was causally related to the use of this drug. To our knowledge, there are no similar reported cases in the literature.
31
Du, Siyue. "Impact de l’expression vasculaire PPAR beta/delta sur la progression des tumeurs et la formation de métastases." Electronic Thesis or Diss., Université Côte d'Azur, 2020. http://www.theses.fr/2020COAZ6015.
Full textAbstract:
Les récepteurs activés par les proliférateurs de peroxysomes (PPARs) sont des récepteurs nucléaires et fonctionnent comme des facteurs de transcription impliqués dans certaines maladies chroniques telles que le trouble du métabolisme lipidique et le cancer, qui incluent PPAR alpha, PPAR beta/delta, PPAR gamma. Parmi eux, PPAR beta/delta a montré des effets explicitement proangiogéniques sur l'angiogenèse physiologique et pathologique. L'angiogenèse est connue pour être une caractéristique du cancer. Il a été suggéré que PPAR beta/delta était impliqué dans la régulation du commutateur angiogénique dans la progression tumorale. Cependant, jusqu'à présent, on ne sait toujours pas dans quelle mesure l'expression de PPAR beta/delta dans l'endothélium tumoral influence la progression tumorale et la formation de métastases. Ainsi, nous avons abordé cette question en utilisant des souris transgéniques avec une surexpression PPAR beta/delta spécifique de l'endothélium conditionnel inductible. Nous avons également induit des tumeurs syngéniques suite à une surexpression spécifique PPAR beta/delta dans les cellules endothéliales. Nous avons observé une néovascularisation tumorale plus élevée et une augmentation de la croissance tumorale et de la formation de métastases dans les tumeurs d'animaux avec une surexpression PPAR beta/delta spécifique vasculaire. Afin d'identifier des cibles moléculaires potentielles en aval de PPAR beta /delta dans l'endothélium tumoral, nous avons trié les cellules endothéliales des tumeurs et effectué le séquençage de l’ARN. Nous avons identifié le facteur de croissance dérivé des plaquettes B (PDGFB), le récepteur beta du facteur de croissance dérivé des plaquettes (PDGFR beta) et le récepteur tyrosine kinase KIT (c-KIT) en tant que nouvelles molécules dépendantes de PPAR beta/delta par l’essai de ChIP. Ainsi, nous avons démontré que l'activation de PPAR beta/delta, quelle que soit son action sur différents types de cellules cancéreuses, favorise la progression tumorale et la formation de métastases grâce à l'amélioration de l'angiogenèse tumoralePeroxisome proliferator- activated receptors (PPARs) are nuclear receptors and function as transcriptional factors involved in some chronic diseases such as lipid metabolism disorder and cancer, which include PPAR alpha, PPAR beta/delta, PPAR gamma. Among them, PPAR beta/delta has exhibited explicitly proangiogenic effects on physiological and pathological angiogenesis. Angiogenesis has been known as a hallmark of cancer. PPAR beta/delta has been suggested to be involved in the regulation of the angiogenic switch in tumor progression. However, until now, it is still unclear to what extent the expression of PPAR beta/delta in tumor endothelium influences tumor progression and metastasis formation. Thus, we addressed this question using transgenic mice with conditional inducible vascular-endothelium specific PPAR beta/delta overexpression. We also induced syngenic tumors following specific PPAR beta/delta overexpression in endothelial cells. We observed higher tumor neovascularization and enhanced tumor growth and metastasis formation in tumors of animals with vascular-specific PPAR beta/delta overexpression. In order to identify potential downstream molecular targets of PPAR beta/delta in tumor endothelium, we sorted endothelial cells from the tumors and performed RNA sequencing. We identified platelet- derived growth factor B (PDGFB), platelet- derived growth factor receptor beta (PDGFR beta) and the receptor tyrosine kinase KIT (c-KIT) as new PPAR beta/delta dependent molecules by ChIP assay. Thus, we demonstrated that PPAR beta/delta activation, regardless of its action on different cancer cell types, promotes tumor progression and metastasis formation through enhancement of tumor angiogenesis
32
Franke, Fabian Christoph [Verfasser], Klaus-Peter [Akademischer Betreuer] Janssen, Bernhard [Gutachter] Küster, Andreas [Gutachter] Jung, and Klaus-Peter [Gutachter] Janssen. "Contribution of the novel tumor suppressor SASH1 and the CRK protein family to tumor progression and metastasis formation / Fabian Christoph Franke ; Gutachter: Bernhard Küster, Andreas Jung, Klaus-Peter Janssen ; Betreuer: Klaus-Peter Janssen." München : Universitätsbibliothek der TU München, 2020. http://d-nb.info/1211725197/34.
Full text
33
Minaskan, Karabid Ninelia [Verfasser], Michael J. [Akademischer Betreuer] Atkinson, Nina H. [Gutachter] Uhlenhaut, and Michael J. [Gutachter] Atkinson. "Identification of the molecular mechanisms promoting neuroendocrine tumor formation / Ninelia Minaskan Karabid ; Gutachter: Nina H. Uhlenhaut, Michael J. Atkinson ; Betreuer: Michael J. Atkinson." München : Universitätsbibliothek der TU München, 2020. http://d-nb.info/121529316X/34.
Full text
34
Sha, Weixiao [Verfasser], Bernhard [Akademischer Betreuer] Brüne, and Dieter [Akademischer Betreuer] Steinhilber. "Formation of PGE 2 in the tumor microenvironment and its impact on tumorigenesis / Weixiao Sha. Gutachter: Dieter Steinhilber ; Bernhard Brüne. Betreuer: Bernhard Brüne." Frankfurt am Main : Univ.-Bibliothek Frankfurt am Main, 2014. http://d-nb.info/1051373425/34.
Full text
35
Ait, Khelifa-Gallois Nadira. "Rôle du cervelet dans la formation d'automatismes moteurs et cognitifs : étude des sujets traités pour tumeur du cervelet." Thesis, Paris 5, 2014. http://www.theses.fr/2014PA05H109.
Full textAbstract:
L'objectif général de cette thèse est d'explorer l'impact des lésions du cervelet sur les séquelles motrices et cognitives des enfants traités pour tumeur du cervelet maligne ou bénigne. En nous basant sur trois études cliniques, nos objectifs généraux ont été (1) d'examiner si ces enfant présentaient des déficits dans l'établissement d'automatismes moteurs et cognitifs, (2) de préciser les facteurs associés aux difficultés d'automatisation et (3) d'examiner l'impact de ces difficultés sur la scolarité et le devenir à long terme de ces enfants. La première étude avait pour objectif spécifique d'examiner le devenir à long terme de 46 adultes et de 18 adolescents traités dans l'enfance chirurgicalement pour un astrocytome pilocytique du cervelet. Elle a mis en évidence un devenir à long terme satisfaisant dans l'ensemble, bien que des difficultés cognitives et motrices aient été rapportées, en particulier par les sujets qui ont le plus réussi leurs parcours scolaires. La perte d'autonomie était associée à des complications postopératoires telles que le mutisme cérébelleux et l'invasion du tronc cérébral. La deuxième étude a porté sur une cohorte de 17 enfants et adolescents traités pour un astrocytome pilocytique cérébelleux. Elle a exploré l'automatisation de la lecture et discuté la théorie cérébelleuse de la dyslexie. Les résultats ont mis en évidence une difficulté de suppression des mouvements articulatoires chez la plupart des sujets qui était associée à un faible indice de Mémoire de Travail Verbale. La troisième étude a porté sur 16 enfants traités pour un astrocytome pilocytique du cervelet et 16 enfants traités pour un médulloblastome. Elle avait pour objectifs (1) d'étudier l'apprentissage moteur et différents automatismes cognitifs intervenant notamment dans la lecture et le calcul mental et (2) de préciser les relations entre les différentes mesures de la difficulté d'automatisation motrice et cognitive. Les résultats ont confirmé la difficulté de suppression des mouvements articulatoires et ont montré que les enfants traités pour tumeur du cervelet se différenciaient des enfants sains de âge par un apprentissage moteur moindre, en particulier avec la main non dominante et par une lenteur en lecture, en calcul mental, en dénomination rapide et en double tâche. Par ailleurs, l'atteinte des noyaux dentelés était liée à une baisse de l'efficience intellectuelle, en particulier chez les enfants traités pour un médulloblastome, à un apprentissage moteur moindre avec la main dominante, à une difficulté de suppression des mouvements articulatoires, et à une lenteur de calcul mental. Ce travail de thèse offre des résultats pionniers dans la compréhension de l'impact des lésions cérébelleuses sur les apprentissages chez l'enfantThe general aim this doctoral dissertation is to explore the impact of cerebellar lesions on motor and cognitive sequelae in children treated for malignant or benign tumor of the cerebellum. In three clinical studies, we in (1) examine whether these children exhibited deficits in motor and cognitive automation, (2) identify factors associated with difficulties in automation and (3) examine the impact of these difficulties on schooling and long-term outcome. The first study examines the long-term outcome of 46 adults and 18 adolescents treated surgically in childhood for cerebellar pilocytic astrocytoma. Most subjects showed a positive long-term outcome, despite report of cognitive and motor difficulties, especially by subjects with successful school careers. The loss of autonomy was associated with postoperative complications, post cerebellar mutism, or invasion of the brain stem. The second study in 17 children and adolescents treated for pilocytic cerebellar astrocytoma aimed to examine the automation of reading and to discuss the cerebellar theory of dyslexia. The results highlighted a difficulty of suppressing articulatory movements in most subjects, associated with low index of Verbal Working Memory. The third study concerned 16 children treated for pilocytic astrocytoma of the cerebellum and 16 children treated for medulloblastoma. Its objectives were to (1) investigate motor learning and different cognitive automations involved in particularly in reading and mental calculation (2) clarify the relationship between different measures of motor and cognitive automation. The results confirmed the difficulty to suppress articulatory movements and showed lower motor learning effect, especially with the non-dominant hand, slowness in reading, mental calculation, rapid naming and dual task. Furthermore, dentate nuclei damage was linked to lower intellectual efficiency (IQ), particularly in children treated for medulloblastoma; to a lesser motor learning for the dominant hand, a difficulty to suppress articulatory movements, and slowness in mental calculation. This work offers pioneer results in understanding the impact of cerebellar lesions in children learning
36
Kosinsky, Robyn Laura [Verfasser], Steven A. [Akademischer Betreuer] Johnsen, Steven A. [Gutachter] Johnsen, Holger [Gutachter] Reichardt, and Heidi [Gutachter] Hahn. "The Cellular Function of USP22 and its Role in Tissue Maintenance and Tumor Formation / Robyn Laura Kosinsky ; Gutachter: Steven A. Johnsen, Holger Reichardt, Heidi Hahn ; Betreuer: Steven A. Johnsen." Göttingen : Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2018. http://d-nb.info/1152437690/34.
Full text
37
Matos, Rodrigues Gabriel Eduardo de. "Suppression of Homologous Recombination by RAD51 Functional Inactivation In Vivo in Mice Replication Stress, DNA Damage, Inflammatory Cytokines and Innate Immune Response In Vivo Suppression of Homologous Recombination Leads to a Systemic Inflammation That Exacerbates Mouse Death Functional Inactivation of RAD51 in Adult Mice Leads to Premature Aging Without Tumor Development Inactivation of Trp53 Accelerates Mouse Death After RAD51 Functional Inactivation in Adult Mice Without Increasing Tumor Formation RAD51 Functional Inactivation Inhibits Mammary Tumor Initiation and Progression in Mice." Thesis, université Paris-Saclay, 2020. http://www.theses.fr/2020UPASL073.
Full textAbstract:
La recombinaison homologue (RH) est un processus conservé dans l'évolution qui joue un rôle de premier plan dans la plasticité du génome, contrôlant l'équilibre de stabilité/diversité génétique. L'étape charnière des RH, c'est-à-dire la recherche d'homologie d'ADN et l'échange de brins, est régi par le filament RAD51-ssDNA (ADN simple brin) qui doit être bien ordonné, donc représentant les espèces actives centrales de la RH. La déficience de la HR est liée au développement de syndromes et cancer chez l’humain. Cependant, puisque Rad51 est un gène essentiel chez la souris, les conséquences de la perturbation fonctionnelle de RAD51 reste à être étudié in vivo. Ici, nous avons développé un forme inductible du dominante négative de RAD51 (SMRAD51) pour poissonnier la RH in vivo. En utilisant des approches biochimiques, nous démontrons que SMRAD51 perturbe les échanges de brins d’ADN dépendant de RAD51 et la formation du filament RAD51-ssDNA. L'expression SMRAD51 conduit à le stresse réplicatif in vitro et in vivo, déclenchant épuisement des progéniteurs. Nous montrons que l’inactivation fonctionnelle de RAD51 chez la souris en croissance (commence 12 à 14 jours après la naissance) déclenche une réponse inflammatoire entraînant la mort de la souris dans quelques jours. Chez la souris adulte, l’inactivation fonctionnelle de RAD51 induit des phénotypes de vieillissement prématuré et diminue la durée de vie avant un possible tumorigenèse. De plus, nous montrons que l'inactivation fonctionnelle de RAD51 inhibe initiation et progression tumorale dans un modèle murin de cancer du sein. Dans l'ensemble, je découvre ici de nouveaux mécanismes pro-vieillissement et anti-tumoraux générés par l'inactivation fonctionnelle de RAD51Homologous recombination (HR) is an evolutionary conserved process that plays a prominent role in genome plasticity, controlling the balance of genetic stability/diversity. The pivotal step of HR,i.e. DNA homology search and strand exchange, is governed by the RAD51-ssDNA (single-stranded DNA) filament that must be well ordered, thus representing the actual active species of HR. HR impairment is linked to human developmental syndromes and cancer. However, since RAD51 is an essential gene in mice, the consequences of functional disruption of RAD51 remain to be studied in vivo. Here we developed an inducible dominant negative form of RAD51 (SMRAD51) to poison HR in vivo. Using biochemical approaches, we demonstrate that SMRAD51 disrupts RAD51-dependent strand-exchange and RAD51-ssDNA filament formation. SMRAD51 expression leads to replicative stress in vitro and in vivo, triggering progenitor exhaustion. We show that functional inactivation of RAD51 in growing mice (starting from 12 to 14 days after birth) triggers a systemic inflammatory response causing mouse death within a few days. Meanwhile, RAD51 functional disruption in adult mice induces premature aging phenotypes and reduced lifespan prior to putative tumorigenesis. In addition, we show that RAD51 functional inactivation inhibits tumor initiation and progression in a mouse model of breast cancer. Overall, here I uncover new pro-aging and anti-tumor mechanisms generated by the functional inactivation of RAD51
38
Saad, Carla Gonçalves Schahin. "Baixos níveis de esclerostina: preditor de processo inflamatório persistente em pacientes com espondilite anquilosante sob terapia anti-TNFα." Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/5/5164/tde-09012013-180110/.
Full textAbstract:
Introdução: Baixas concentrações séricas de esclerostina foram descritas em pacientes com Espondilite Anquilosante (EA). No entanto, não existem dados sobre a importância deste inibidor da via de sinalização Wnt em pacientes com EA durante o tratamento com anti fator de necrose tumoral alfa (TNFa). Objetivos: Avaliar longitudinalmente os níveis séricos de esclerostina e sua associação com inflamação e densidade mineral óssea (DMO) em pacientes com EA em tratamento com anti-TNFa. Métodos: Trinta pacientes com EA em atividade foram avaliados no início, 6 e 12 meses, após terapia anti-TNFa em relação aos parâmetros clínicos (BASDAI, BASFI, BASMI e ASQoL), marcadores inflamatórios e dano radiológico basal (mSASSS). Trinta indivíduos saudáveis pareados por idade e sexo constituíram o grupo controle. As análises laboratoriais de esclerostina e da ligação de esclerostina ao receptor LRP6 e a DMO foram realizadas nos pacientes nos mesmos períodos de avaliação e comparadas aos controles. Resultados: Na avaliação inicial, pacientes com EA apresentavam menores concentrações séricas de esclerostina [60,5 (32,7) vs. 96,7 (52,9) pmol/l,P=0,002] e níveis similares de ligação de esclerostina ao receptor LRP6 (P=0,387) em relação aos controles. Foi observado melhora do BASDAI, BASFI, BASMI, ASQoL comparando tempo basal vs. 6 vs. 12 meses (P<0,01). Concomitantemente, observou-se um aumento gradual da DMO da coluna lombar (P<0,001) e no início do estudo os pacientes apresentavam uma correlação positiva entre avaliação radiológica basal (mSASSS) e a DMO da coluna lombar (r=0,468, P<0,01). Foi observada também uma redução dos marcadores inflamatórios comparando tempo basal vs. 6 vs. 12 meses (P<0,01). Os níveis de esclerostina aumentaram progressivamente após o tratamento com anti-TNFa [60,5 (32,7) vs. 67,1 (31,9) vs. 72,7 (32,3) pmol/l, P<0,001]. Entretanto, após 12 meses de terapia anti-TNFa as concentrações séricas de esclerostina permaneceram significativamente mais baixos em relação os controles [72,7 (32,3) vs. 96,7 (52,9) pmol/l, P=0,038]. Além disso, aos 12 meses, os níveis séricos de esclerostina ficaram mais baixos nos 10 pacientes que ainda apresentavam proteína C reativa elevada (PCR=5mg/l), comparados aos pacientes que apresentaram normalização dos níveis de PCR (P=0,004). Interessantemente, estes 10 pacientes com inflamação persistente já apresentavam concentrações séricas mais baixas de esclerostina quando comparados aos demais pacientes (P=0,023) antes do tratamento com anti- TNFa. A análise de regressão logística demonstrou que os pacientes com EA com níveis baixos de esclerostina apresentam um risco aumentado de apresentar PCR alta após 12 meses de tratamento (odds ratio = 7,43, 95% IC 1,23-45,01, P=0,020) quando comparados aos pacientes com níveis altos de esclerostina no tempo basal. Conclusão: Concentrações persistentemente baixas de esclerostina estão associados a inflamação contínua em pacientes com EA tratados com terapia anti-TNFa.Introduction: Sclerostin levels have been reported to be low in ankylosing spondylitis (AS), but there is no data regarding the possible role of this Wnt inhibitor during anti tumor necrosis factor alpha (TNFa) therapy. Objectives: The present study longitudinally evaluated sclerostin levels, inflammatory markers and bone mineral density (BMD) in AS patients under anti-TNFa therapy. Methods: Thirty active AS patients were assessed at baseline, 6 and 12 months after anti-TNFa therapy regarding clinical parameters (BASDAI, BASFI, BASMI and ASQoL), inflammatory markers, BMD and baseline radiographic damage (mSASSS). Thirty age- and sex-matched healthy individuals comprised the control group. Patients\' sclerostin levels, sclerostin binding LRP6 and BMD were evaluated at the same time points and compared to controls. Results: At baseline, AS patients had lower sclerostin levels [60.5 (32.7) vs. 96.7 (52.9) pmol/l, P=0.002] and comparable sclerostin binding to LRP6 (P=0.387) than controls. Improvement of BASDAI, BASFI, BASMI, ASQoL was observed at baseline vs. 6 vs. 12 months (P<0.01). Concomitantly, a gradual increase in spine BMD (P<0.001) and a positive correlation between baseline mSASSS and spine BMD was found (r=0.468, P<0.01). Inflammatory parameters reduction was observed comparing baseline vs. 6 vs. 12 months (P<0.01). Sclerostin levels progressively increased [60.5 (32.7) vs. 67.1 (31.9) vs. 72.7 (32.3) pmol/l, P<0.001] after anti-TNFa treatment. At 12 months, the sclerostin levels remained significantly lower in patients compared to controls [72.7 (32.3) vs. 96.70 (52.85) pmol/l, P=0.038]. Moreover, sclerostin serum levels at 12 months were lower in the 10 patients with high CRP (=5mg/l) compared to the other 20 patients with normal CRP (P=0.004). Of note, these 10 patients with persistent inflammation also had lower sclerostin serum levels at baseline compared to the other patients (P=0.023). Univariate logistic regression analysis demonstrated that AS patients with lower sclerostin serum levels had an increased risk to have high CRP at 12 months (odds ratio=7.43, 95% CI 1.23-45.01, P=0.020) than those with higher sclerostin values. Conclusion: Persistent low sclerostin levels may underlie continuous inflammation in AS patients under anti-TNFa therapy.
39
Varela, Mendes Ribeiro A. S. "A novel model of tumour formation in NF1." Thesis, University College London (University of London), 2012. http://discovery.ucl.ac.uk/1352630/.
Full textAbstract:
Neurofibromatosis type 1 (NF1) is a common genetic disorder that predisposes to the development of heterogeneous tumours of Schwann cell origin, termed neurofibromas. Neurofibromas are thought to arise from a combination of genetic events – loss of the Ras-GAP neurofibromin in the Schwann cell lineage – and microenvironmental cues. Schwann cells are specialised cells that ensheath and myelinate the axons in the peripheral nervous system (PNS). In the adult they are present in a quiescent state, however following damage to the PNS they have a remarkable ability to regenerate. Distal to the site of injury, Schwann cells dedifferentiate to a progenitor-like state, in which they contribute to nerve repair by recruiting a robust inflammatory response and helping axons return to their targets. Work from our laboratory has shown that activation of the Ras/Raf/ERK pathway plays a central role in driving the switch in Schwann cell state from a fully differentiated to a proliferating, “progenitor-like” cell. Crucially, neurofibromas resemble injured nerves in that they are composed of a mixture of inflammatory cells and Schwann cells that are found dedifferentiated and dissociated from axons, suggesting that deregulation of Ras/ERK may trigger tumourigenic events. In this thesis I present work on how the Ras/Raf/ERK pathway may be regulated in Schwann cells. I show that the phosphatase MKP3 may be involved in controlling the levels of ERK activity in Schwann cells during differentiation and following nerve injury. I also describe a new model for neurofibroma formation. Using transgenic mice I show that Nf1 loss in adult, myelinating Schwann cells has no effect on peripheral nerves and does not induce tumourigenesis. However, when coupled with an injury, the mice developed tumours at a high frequency. Furthermore, I show that in the absence of Nf1, ERK signalling is deregulated upon injury, implicating this pathway in the tumour formation. This may have therapeutic relevance, which is currently being tested in our animal model. In addition, we observed that tumours only arise at the wound site, despite Schwann cells dedifferentiating along the length of the nerve. This strongly implies that the microenvironment is a crucial player in the outcome of Nf1 loss and reveals this new animal model as a promising system to further dissect molecular events involved in tumourigenesis.
40
Quist, Sven Roy. "Role of Rac1 signalling in epidermal tumour formation." Thesis, University of Cambridge, 2014. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.708007.
Full text
41
Miremadi, Ahmad. "Role of α6β4 integrin in epidermal tumour formation." Thesis, University of Cambridge, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.608785.
Full text
42
Kocialkowski, Sylvia. "Investigation of genetic abnormalities underlying tumour formation in mice." Thesis, University of Oxford, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.386615.
Full text
43
Turner, Rhodri Thomas Owain. "Role of complement in tumour formation : friend or foe?" Thesis, Cardiff University, 2010. http://orca.cf.ac.uk/54370/.
Full textAbstract:
The aims of this thesis were to investigate and build on recent reports implicating the complement (C) system in tumour growth and progression. The respective contributions of specific C components and regulators to this effect were assessed by the use of two tumour induction protocols. Firstly, the chemical carcinogen 3-methylcholanthrene (3-MCA) was used to induce tumours in wild type mice and in animals deficient in C1q, C3 or double deficient in CD55 and CD59. Deficiency in the classical pathway of activation (C1q"7') or in the central component (C3"7') conferred a statistically significant protective effect against 3-MCA-induced tumourigenesis, suggesting that a fully functional C system was important for promotion of tumour progression in vivo. Additionally, a protective effect was observed in CD55"7".CD59"7' mice indicating an important role for C-regulatory proteins (CRegs) in tumour progression. In the second approach, novel fibrosarcoma lines were generated from 3- MCA-induced tumours. WT, C1q"7", C3"7" and CDSS.CDS lines were cloned and tested for specific characteristics including CReg expression, synthesis of C3 and susceptibility to C-attack. Few differences were observed between lines of different genotypes though expression of terminal pathway regulator CD59 was observed in C3"7" lines only. Re-inoculation of WT and C3 lines showed no differences between the groups with comparable tumour incidence and growth rates observed. Additionally, the effect of C on progression of a pre-characterised WT fibrosarcoma line was tested by inoculation into WT and C-deficient mice. Tumours inoculated into C1q"7", C3"7" and CD55"7'.CD59"7" mice were shown to exhibit comparable growth characteristics to those in WT controls. However, depletion of the terminal pathway component C5 using a monoclonal antibody (mAb) was shown to inhibit tumour progression. Treatment of mice with anti- C5 mAb conferred a statistically significant protective effect to these mice and suggests a role for C in driving tumour pathology. In conclusion, work in this thesis demonstrates an important pro-tumour role for C whereby activation of C can result in enhanced tumour progression. Additionally, expression of the CRegs CD55 and CD59 on host cells rather than tumour cells contributes to tumour proliferation. A pro-tumour role for C is contrary to current dogma but supports an alternative hypothesis whereby cell activating effects may provide a selective advantage to tumour cells following C-activation.
44
Arwert, Esther Norine. "The contribution of the inflammatory microenvironment to wound-induced epidermal tumour formation." Thesis, University of Cambridge, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.609159.
Full text
45
Ellis, Michael J. "Synthetic routes to polycyclic acridines : potential anti-tumour agents." Thesis, University of Nottingham, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.366289.
Full text
46
Hutchins, Marilyn K. "Formative development of a parent tutor program." Diss., Virginia Polytechnic Institute and State University, 1989. http://hdl.handle.net/10919/54200.
Full textAbstract:
The procedural problem of this action research study was to develop a parent tutor program to teach parents how to work more effectively with the homework process. The review of literature examined (a) parent involvement, (b) parent education, (c) homework, and (d) curriculum development. A formative evaluation methodology involved four phases: (a) development, (b) implementation, (c) assessment, and (d) revision. The researcher used two curriculum software packages, Peaks CourseBuilding Software and PEAKSolutions LessonBuilding Software™. developed by PEAKSolutions and Vogler in 1989, to prepare a curriculum resource guide containing leader (counselor) guidelines, syllabus, and nine lesson plans. A foundation was provided by a selfhelp book on minimizing the homework hassle entitled Parents as Tutors, written by Vogler and Hutchins in 1988. Six elementary counselors formed an advisory panel to provide formative evaluation/validation of the program during the development and revision phases.
The subjects were groups of parents who volunteered to participate in parent tutor groups at three elementary schools in southwest Virginia. Four instruments were designed and used in the formative evaluation process. One was a questionnaire completed by the advisory panel. The others were completed by the participants at the beginning, during, and at the end of the parent education groups.
All parents who completed the parent tutor program indicated they experienced positive involvement in the homework process for themselves as well as benefits for their children. Conclusions related to parent participant goals for and problems with the homework process, reasons for parent group attrition, leader role and parent group strategies, and the importance of evaluative data. Recommendations were provided for parent tutor groups and future research. A counselor oriented parent tutor curriculum resource guide including a syllabus and nine comprehensive lesson plans with fieldtested revisions are included in the dissertation.Ed. D.
47
Wani, Mohan Ramchandra. "Regulation of osteoclast formation and activation by TRANCE and prostaglandin Eâ†2." Thesis, St George's, University of London, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.341938.
Full text
48
Gilbert, P. X. "Study of the role of an oncogene in the formation of tumours." Thesis, University of Oxford, 1986. http://ora.ox.ac.uk/objects/uuid:62fe804d-1208-454a-96cb-608c2491631b.
Full textAbstract:
The aim of this study was to examine the claim that a single, mutant oncogene can transform NIH 3T3 mouse fibroblasts into transformed, tumorigenic cells, acting in a genetically dominant fashion. A c.Ha-ras 1 oncogene, cloned from the EJ human bladder carcinoma cell line, was inserted into a shuttle vector carrying the selectable marker gene gpt, which encodes the enzyme XPRT (xanthine-guanine phosphoribosyl transferase). This construct, pSV2gptEJ, was transfected into NIH 3T3 cells by the calcium phosphate precipitation method and cells which had incorporated the plasmid were selected by growth in mycophenolic acidcontaining medium, to which gpt confers resistance. A number of clonal lines were established and their tumorigenicity tested. Tumour cell lines derived from these transfectants were back-selected using 2-thioxanthine, a cytotoxic analogue of the xanthine-guanine phosphoribosyl transferase substrate, to isolate clones which no longer contained functional pSV2gptEJ sequences. Six sub-clones which did not express detectable levels of the ras oncogene product, p21H.ras , were obtained. All were judged to be less transformed than the transfected parent cells: they appeared morphologically normal, were more serum-sensitive, showed clear saturation densities and were more anchorage-dependent. Three of these sub-clones were found to be tumorigenic at all sites tested. Cytological examination of the NIH 3T3 transfectants revealed that significant perturbation of their chromosome complement accompanied transfection. The transfection process, in the absence of DNA or with pSV2gpt alone, was found to be capable of transforming NIH 3T3 cells. Finally, a brief investigation of the effect of a "functional EJ-ras gene upon the differentiated phenotypes of these cell lines was attempted by comparing their ability to produce an extracellular matrix.
49
Rutkauskaitė, Dileta. "Comparative analysis of CT colonography data and their assessment in the examination of tumor formations." Doctoral thesis, Lithuanian Academic Libraries Network (LABT), 2014. http://vddb.library.lt/obj/LT-eLABa-0001:E.02~2014~D_20141230_152838-86119.
Full textAbstract:
About half of million deaths caused by colorectal cancer (CRC) has been reported worldwide every year. Programmes for early diagnosis of CRC has reduced mortality due to this disease, as the cancer is diagnosed in earlier stages which can be treated more successfully. Programme for early CRC diagnosis in Lithuania has been based on the faeces occult blood test (FOBT). If positive FOBT result is obtained, patients should be referred for colonoscopy (CS) examination. Based on the data from the National Health Fund, during the first three years CS examination was carried out for a little bit more than half of the patients participating in the programme and presenting with positive FOBT result. Aiming to improve accuracy of CRC diagnostics we have suggested alternative CS examination – computed tomography colonography (CTC).
The aim of our study was to establish diagnostic value of CTC examination in the identification of neoplastic alterations in the patients with positive FOBT result and to specify factors having influence on the examination quality. CTC examinations were carried out and their results were compared with the findings of CS.
We discovered that CTC is of high diagnostic value for detection of lesions sized ≥ 6 mm and of very high diagnostic value for detection of large ( ≥ 10 mm) polyps in a colon. We found out that the length of colon had no influence on how patients tolerated this examination and on patients well-being during CTC procedure, and colon cleaning... [to full text]Pasaulyje kasmet nuo storosios žarnos vėžio (SŽV) miršta apie pusė milijono žmonių. SŽV ankstyvosios diagnostikos programos sumažina mirtingumą nuo šios ligos, nes vėžys tada yra aptinkamas anksčiau ir galima jį lengviau išgydyti. Lietuvoje SŽV ankstyvosios diagnostikos programa yra paremta slapto kraujo išmatose nustatymo testu (FOBT). Po teigiamo FOBT atsakymo pacientai yra nukreipiami kolonoskopijai (KS). Valstybinės ligonių kasos duomenimis per pirmuosius trejus metus iš pacientų, dalyvavusių programoje, kuriems nustatytas teigiamas FOBT, iš jų tik kiek daugiau nei pusei pacientų atlikta KS. Norint dažniau diagnozuoti SŽV, pasiūlėme alternatyvų KS tyrimą - kompiuterinės tomografijos kolonografiją (KTK). Taikydami KTK ir lygindami jos rezultatus su KS, norėjome išsiaiškinti KTK tyrimo diagnostinę vertę nustatant neoplastinius pakitimus pacientams su teigiamu FOBT bei nustatyti tyrimo kokybei darančius įtaką faktorius. Nustatėme, kad KTK pasižymi didele diagnostine verte nustatant ≥6 mm dydžio pakitimus bei labai didele diagnostine verte nustatant didelius (≥10 mm) polipus, storojoje žarnoje. Nustatėme, kad storosios žarnos ilgis neturi įtakos KTK tyrimo tolerancijai ir paciento savijautai KTK metu, o žarnos išsivalymo kokybė prieš KTK tyrimą nepriklauso nuo anatominių storosios žarnos savybių – tokių, kaip ilgis. Išsiaiškinome, kad KTK tyrimas yra jautrus nustatant storosios žarnos neoplastines adenomas ir vėžį, bet nesiekia KS tyrimo jautrumo, todėl KTK taikyti... [toliau žr. visą tekstą]
50
Thomson, Travis Carle. "The role of TUDOR in «Drosophila» polar granule assembly and germ cell formation." Thesis, McGill University, 2008. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=19231.
Full textAbstract:
Germ cells are a totipotent stem cell line where meiosis occurs; without germ cell formation sexual and types of asexual reproduction cannot occur. Drosophila germ cell formation depends on a specialized cytoplasm which is at the posterior of early embryos. The germ plasm in Drosophila contains electron dense structures called polar granules. Similar electron dense structures are found in the germ line of many metazoan species. This thesis examines the polar granule component, TUDOR and its molecular function in Drosophila germ cell formation and polar granule assembly. I created a null allele of tud and found that without TUDOR, embryos are incapable of forming germ cells, while some embryos had normally patterned abdomens. As TUDOR was dispensable for somatic functions but central to germ cell formation, I isolated TUDOR containing complexes from embryos. I then compared the proteins found in my TUDOR complexes to those in VASA complexes to determine which TUDOR complex components are polar granule constituents. I examined five proteins in the TUDOR and VASA complexes, TER94, AUBERGINE, Me31B, eIF4A and Pyruvate Kinase. Reduction of VASA or TUDOR from the early embryo along with TER94, Me31B, eIF4A or AUBERGINE results in a decrease in germ cell formation. As well, TER94, Me31B, eIF4A and AUBERGINE all localize to polar granules. Three of the polar granule components we isolated, Me31B, eIF4A and AUBERGINE, are proteins typical of P bodies, sites of mRNA metabolism, suggesting that polar granules might be related to P bodies specific. Interestingly, immuno-electron micrographs of TER94, an endoplasmic reticulum (ER) component, showed that polar granules can associate with ER. We also show Pyruvate Kinase, a glycolytic proteinLes cellules germinales sont des cellules souches, totipotentes, dans lesquelles se produit la méiose et qui sont nécessaires à la reproduction sexuelle et certains cas de reproduction asexuelle. Chez la drosophile, la formation des cellules germinales est liée à l'assemblage du cytoplasme germinal. Ce cytoplasme distinct contient des granules électron-denses appelées granules polaires. Les études présentées dans cette thèse examinent le rôle de TUDOR, un composant des granules polaires, au cours de l'assemblage des granules polaires et lors de la formation des cellules germinales. J'ai créé un allèle nul de tud qui m'a permis de déterminer que TUD est nécessaire à l'établissement des cellules germinales alors qu'il est partiellement dispensable à la formation de l'abdomen. Due à l'importance de TUDOR durant l'établissement des cellules germinales, j'ai d'isolé le complexe de protéines associées à TUDOR. J'ai comparé les protéines ainsi isolées à celles du complexe de VASA afin d'identifier des composants des granules polaires. J'ai ainsi étudié cinq protéines appartenant aux complexes de TUDOR et VASA soit TER94, AUBERGINE, Me31B, eIF4A et Pyruvate Kinase. La réduction de TUDOR ou de VASA en combinaison avec la réduction de TER94, Me31B, eIF4A ou AUBERGINE cause une baisse dans le nombre de cellules germinales formées. De plus, TER94, Me31B, eIF4A et AUBERGINE sont observés dans les granules polaires. Trois de ces composants soit Me31B, eIF4A et AUBERGINE sont des protéines également trouvées dans les « P-bodies », sites de métabolisme d'ARNm, ce qui suggère que les granules polaires sont un type de « Pbodies ». Des images de microscopie immuno-électronique de TER94, une protéine