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1
Broers, Anna Elisabeth Clasine. "Interleukin-7 and hematopoietic stem cell transplantation: beyond the thymus." [S.l.] : Rotterdam : [The Author] ; Erasmus University [Host], 2007. http://hdl.handle.net/1765/10697.
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Amos, Claire. "Studies on the mechanisms of IL-7 induced cell survival." Thesis, University of Sheffield, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.312782.
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Deiser, Katrin. "Impact of IL-7 signaling on adoptive T cell therapy." Doctoral thesis, Humboldt-Universität zu Berlin, Lebenswissenschaftliche Fakultät, 2016. http://dx.doi.org/10.18452/17419.
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Das Zytokin Interleukin-7 (IL-7) ist für die Entstehung und das Überleben reifer T Zellen von zentraler Bedeutung. Die Gabe von IL-7 führt sowohl in der Maus als auch im Menschen zu erhöhten T Zellzahlen und einem veränderten T Zellphänotyp. Folglich könnte sich die therapeutische Gabe von IL-7 bei Patienten mit geschwächtem Immunsystem positiv auswirken. Diese Hypothese wird derzeit in mehreren klinischen Studien untersucht. Bisher wurde allerdings nur die Wirkung von IL-7 auf T-Zellen studiert. Zu dessen Wirkung auf andere Immun- oder Stromazellen sowie deren IL-7-abhängigen Beitrag zur Regulation der T-Zellhomöostase ist nur wenig bekannt. Daher war es Ziel der Arbeit, den Einfluss einer therapeutischen Gabe von IL-7 auf adoptiv-transferierte T-Zellen in IL-7-Rezeptor (IL-7R)-kompetenten und defizienten lymphopenischen Mäusen zu studieren. Die Untersuchungen bestätigen, dass die Gabe von IL-7 T-Zellantworten unterstützt, zeigen jedoch auch, daß viele dieser Effekte von IL-7R-exprimierenden Wirtszellen abhängig sind. Dies weist darauf hin, dass IL-7R-vermittelte Signale in Wirtszellen indirekt T-Zellantworten beeinflussen. Zudem zeigte sich, dass effiziente anti-Tumor-T Zellantworten von IL 7R-vermittelten Signalen in Wirtszellen abhängen. Vor allem nicht-hämatopoetische Wirtszellen fungieren hier als Regulatoren der IL-7-Therapie-vermittelten T Zelldifferenzierung. Unsere Ergebnisse bestätigen außerdem, dass Stromazellen in verschiedenen Organen il-7 exprimieren und zeigen darüber hinaus, dass diese Zellen durch die Gabe von IL-7 beeinflusst werden. Wir folgern daraus, dass die Effekte der IL-7-Therapie auf T Zellhomöostase teilweise indirekt über il-7-exprimierende Stromazellen vermittelt werden. Um diese Zellen genauer identifizieren und untersuchen zu können, haben wir ein neues transgenes Mausmodell charakterisiert, was es erleichtern wird, die beteiligten molekularen Signalwege zu analysieren und den Erfolg der adoptiven T Zelltherapie zu verbessern.<br>Interleukin-7 (IL-7) is an essential cytokine required for the development and maintenance of mature T cell. Its availability is limited under normal conditions, but rises during lymphopenia, leading to increased T cell proliferation. The administration of recombinant IL-7 to normal or lymphopenic mice and humans results in increased T cell numbers and altered T cell phenotype. Hence, IL-7 administration could mediate therapeutic benefits in immunocompromised patients and is currently tested in several clinical trials. However, besides its well-studied effects on T cells little is known about the effect of IL-7 on other immune and non-immune cells and their influence on T cell homeostasis. Therefore, we evaluated the effect of IL-7 therapy on adoptively transferred T cells in IL-7 receptor (IL-7R)-competent and IL-7R-deficient lymphopenic mice. We confirm the benefits of IL-7 therapy on T cell responses but additionally show that many of these effects are dependent on IL-7R expression by host cells, indicating that IL-7R signaling in host cells modulates T cell responses. We show that efficient T cell responses against cancer are dependent on host IL-7R signaling. Based on studies in bone-marrow chimeric mice, we identify non-hematopoietic host cells as main regulators of IL-7 therapy-modulated T cell differentiation. We conclude from these data that IL-7 therapy affects non-hematopoietic stromal cells that modulate the success of adoptive T cell therapy. Our results confirm that stromal cells in various organs express il-7 and show that these cells are targeted by IL-7 therapy in vivo. Hence, we propose that il-7-expressing cells regulate IL-7 therapy-modulated T cell homeostasis. To identify and study these il-7 expressing stromal cells in more detail, we characterized a new transgenic mouse model that will facilitate determining the molecular pathways to improve the success of adoptive T cell therapy.
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Smart, Fiona May. "IL7 receptor signalling during B cell development." Thesis, University of Cambridge, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.313900.
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Crisby, Milita. "Cell death in atherosclerosis /." Stockholm, 1998. http://diss.kib.ki.se/1998/91-628-3191-7/.
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Liu, Renyan. "Synergistic growth inhibition and enhancement of cell death by combination of Melanoma Differentiation Associated gene-7 (MDA-7/IL-24) and cisplatin in ovarian cancer cell lines." VCU Scholars Compass, 2009. http://scholarscompass.vcu.edu/etd/7.
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Ovarian cancer is the most lethal gynecological malignancy among women. The current first-line treatments for ovarian cancer are cisplatin, carboplatin and paclitaxel. However, resistance to these platinum-based drugs occurs in the large majority of initially responsive tumors, resulting in fully chemoresistant, fatal disease. Therefore, the resistance to cisplatin therapy has been a critical hurdle in the management of recurrent ovarian cancer. The mechanisms responsible for cisplatin resistance are not completely understood. In the search for new therapies to overcome/bypass cisplatin resistance, melanoma differentiation gene-7 (MDA-7) IL-24, which is a new cytokine, has anti-cancer efficacy by suppressing cell growth and inducing apoptosis in a broad range of tumor cells and does not induce any toxicity in normal cells, thus, making it a potentially effective therapeutic gene for ovarian cancer. The purpose of this study was to evaluate the potential therapeutic efficacy of MDA-7 to treat ovarian carcinoma. Since adenoviral-mediated MDA-7 gene therapy has been shown to be well tolerated and showed biological activity in clinical studies in the context of other carcinomas we assessed the anticancer effects of Ad.mda-7 and in combination with cis-platinum on ovarian cancer cells. Our results show that the purified recombinant MDA-7 protein, GST-MDA-7, and Ad.mda7 virus (5) induced growth arresst and apoptosis in ovarian cancer cells. However, the apoptosis induction was low and directly correlated with infectivity of Ad.mda-7 virus (5). The use of a modified Ad.mda-7 virus type5, Ad.mda-7 virus type(5/3), inhanced infectivity and significantly enhanced ovarian cancer cell killing in human ovarian cancer cell lines in vitro compared to unmodified Ad.mda-7 virus, Ad.mda-7 virus type5. Also Ad-mda7 synergizes with cis-platinum in vitro and enhances ovarian cancer cell death. Taken together, these findings demonstrate that MDA-7 is capable of promoting growth suppression and inducing cell death in ovarian cancer cells, at least OVCAR cells and support the pharmacological interest of the combination of MDA-7 and cis-platinum.
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Huang, Yu-Ting. "The regulatory role of Pax6 on cell division cycle associated 7 and cortical progenitor cell proliferation." Thesis, University of Edinburgh, 2017. http://hdl.handle.net/1842/29573.
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Forebrain development is controlled by a set of transcription factors which are expressed in dynamic spatiotemporal patterns in the embryonic forebrain and are known to regulate complex gene networks. Pax6 is a transcription factor that regulates corticogenesis and mutations affecting Pax6 protein levels cause neurodevelopmental defects in the eyes and forebrain in both humans and mice. In previous studies, it was shown that the graded expression pattern of Pax6 protein, which is high rostro-laterally to low caudo-medially in the cerebral cortex, is critical for its control of cell cycle progression and proliferation of cortical progenitors. However the underlying mechanisms are still unclear. Based on a microarray analysis carried out in our laboratory, a number of cell cycle-related candidate genes that may be affected by Pax6 have been identified. One such gene, Cell division cycle associated 7 (Cdca7) is expressed in a counter-gradient against that of Pax6. In my current study, I found that Cdca7 mRNA expression in the telencephalon is upregulated in Pax6 null (Small eye) mutants and downregulated in mice that overexpress PAX6 (PAX77) across developing time points from E12.5 to E15.5. There are several potential Pax6 binding motifs located in the genomic locus upstream of Cdca7. However, by chromatin immunoprecipitation, it is showed that none of the predicted binding sites are physically bound by Pax6. Promoter luciferase assays using fragments combining five suspected binding motifs show that Pax6 is functionally critical. Cdca7 is also identified as a Myc and E2F1 direct target and is upregulated in some tumours but its biological role is not fully understood. Current work using in utero electroporation to overexpress Cdca7 around the lateral telencephalon, where Cdca7 expression levels are normally low, tested the effects on the proliferation and differentiation of cortical progenitor cells in this region. In E12.5 mice embryos, overexpression of Cdca7 protein causes fewer intermediate progenitor cells and post-mitotic neurons to be produced but these effects were not found in E14.5 embryos. This result implies that Cdca7 may affect cell fate decision during cortical development.
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Eng, Jamei Raena. "Localization of anthracyclines in drug resistant human MCF-7 breast cancer cells." Thesis, University of Ottawa (Canada), 2007. http://hdl.handle.net/10393/27841.
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Multidrug resistance (MDR) commonly occurs during the treatment of cancer. Current research has focused mostly on the role of drug transporters, as the main mechanism of MDR; however, few have demonstrated a definite link between the expression or function of drug transporters and MDR in cancer patients.
Anthracyclines such as doxorubicin and epirubicin, autofluoresce and can be monitored by confocal microscopy. Two of the four resistant cell fines generated in our lab: the MCF-7EPI cells and to some extent MCF-7 DOX cells, exhibit a localization defect, whereby epirubicin is localized primarily in the cytoplasm rather than the nucleus. This drug localization defect temporally correlated with the onset of drug-resistance during selection for drug resistance in these cell lines. Consistent with the possible sequestration of drugs into acidic vesicles, acridine orange staining has revealed the presence of aggregates of acidified vesicles in the perinuclear region of MCF-7EPI cells. However, co-localization experiments using a number of intracellular organelle markers determined that epirubicin was localized to lysosomes and not consistently to acidic vesicles. An inhibitor of vacuolar H+ ATPase, was unable to restore the localization of epirubicin to the nucleus. Immunofluorescence using an ABCB1 antibody revealed the localization of ABCB1 predominantly in the plasma membrane and to some extent in the perinuclear region of MCF-7EPI cells. Nevertheless, inhibitors of this transporter failed to restore localization of epirubicin to the nucleus. Taken together, these findings strongly suggest that the acquisition of epirubicin resistance in breast tumour cells may involve the P-glycoprotein independent sequestration of drug into lysosomes. These lysosomes need not be acidic, nor does the removal of acid vesicles by inhibition of vacuolar H+ ATPases block the sequestration of drug into lysosomes.
9
Richard, Christina. "Mechanism of inhibition of MCF-7 cell proliferation by alkyllysophospholipids (ALPs)." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape7/PQDD_0002/MQ41763.pdf.
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Petty, Aaron. "Novel MIG-7 expression increases tumor cell invasion and tumor progression." Online access for everyone, 2008. http://www.dissertations.wsu.edu/Thesis/Spring2008/a_petty_040908.pdf.
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Ng, Shyh Chang. "Regulation of Stem Cell Metabolism by the Lin28/let-7 Axis." Thesis, Harvard University, 2013. http://dissertations.umi.com/gsas.harvard:11217.
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My PhD thesis is focused on two fundamental aspects of stem cell metabolism: (1) the role of Lin28 in programming stem cell metabolism, and (2) how metabolism in turn fuels and governs pluripotency. Our studies led us to discover that the stem cell factor Lin28a promotes gigantism by enhancing glucose metabolism in mice, coinciding with discoveries that LIN28B polymorphisms influence height variation in human GWAS. Subsequently, we discovered that the Lin28/let-7 pathway controls glucose metabolism by orchestrating the upregulation of multiple insulin-PI3K-mTOR components, particularly in skeletal muscle progenitors. Since let-7 accumulates with aging, our discoveries suggest that let-7 could represent a new drug target for treating insulin resistance and type 2 diabetes during aging. During these studies, we also observed that Lin28a enhances tissue regeneration in adulthood. Regeneration capacity has long been known to decline with aging, but why juvenile organisms show enhanced tissue repair had remained unexplained. We found that Lin28a reactivation improved the regrowth of skin, hair, cartilage, bone and mesenchyme after injuries. Let-7 repression was necessary but insufficient to explain these phenotypes. In parallel, Lin28a bound to and enhanced the translation of mRNAs for several oxidative enzymes, thereby increasing OxPhos. Lin28a-mediated tissue repair was negated by OxPhos inhibition, whereas a pharmacologically-induced increase in OxPhos promoted wound repair. Thus, Lin28a enhanced tissue regeneration in adults by reprogramming cellular bioenergetics. My interest in the central principles of stem cell metabolism also led us to map the metabolic pathways associated with pluripotency during iPS reprogramming and Lin28/let-7 perturbation. Surprisingly, we found that Thr-Gly-S-adenosylmethionine (SAM) metabolism consistently showed the best correlation with pluripotency. 13Carbon isotope metabolomics further revealed that Thr was catabolized to generate Gly and acetyl-CoA, and ultimately SAM - essential for all methylation reactions. Thr is required for SAM and histone H3K4 methylation in mouse ESCs, thus regulating the open euchromatin and pluripotency of ESCs. Our study shed light on a novel amino acid pathway in stem cells, and demonstrated that metabolic conditions can direct cell fate. In summary, my work has helped us to understand how we can reprogram and manipulate metabolic networks to regulate stem cell homeostasis.
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Belusa, Roger. "Role of Na⁺, K⁺-ATPase in cell adhesion and cell volume regulation : mutagenesis of Na⁺, K⁺-ATPase and transfection in embryonic kidney cell line /." Stockholm, 2001. http://diss.kib.ki.se/2001/91-628-4874-7/.
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Song, Cha-Kyong. "Social Status-Dependent Changes in Behavior and Neurogenesis in the Crayfish Procambarus Clarkii." Digital Archive @ GSU, 2006. http://digitalarchive.gsu.edu/biology_diss/7.
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Crayfish (Procambarus clarkii) form dominance hierarchies, which are patterns of repeated fights with expected outcomes of winner and loser. Establishment of hierarchies allows dominants the first access to limited resources over subordinates, and leads to behavioral and cellular changes corresponding to the social status. Here, the animals¡¯ responses to an unexpected unilateral touch, a non-social stimulus, were examined with respect to their social status and to their social context. Isolates oriented to the stimulus source with raised claws and elevated posture. Dominants also oriented to the stimulus both when tested alone and in the presence of a subordinate. Subordinates oriented to the stimulus while separated from their familiar dominant partner; however, they avoided it when tested while paired with the dominant. In subsequent tests first while semi-separated from the dominant and later while fully separated, the same subordinates displayed more orienting responses as the duration of post-fight separation increased. These results suggest that the lingering effects of recent social experience influence the behavior of subordinate animals. During fights, crayfish release urine toward each other, providing critical chemosensory cues for establishing hierarchies. Throughout the lifespan, new neuronal precursors are added into clusters of olfactory local and projection interneurons (clusters 9 and 10). Here, the effect of pair-wise social experience on neurogenesis in these brain regions was examined using the proliferation marker bromodeoxyuridine. Groups of proliferating cells in clusters 9 and 10 formed distinctive comma shapes. The BrdU-positive nuclei in the head part of the comma were smaller and more circular than those in the tail part of the comma. Subordinates had fewer new neuronal precursors surviving in cluster 9 after 14 days than did dominants. Mitotic activity was not influenced by social status. The effect of social experience on neurogenesis remained when the effect of body growth rate on neurogenesis was removed. In conclusion, social domination enhances cell survival compared to social subordination. Although the function of these surviving newborn neuronal precursors is unknown they may enhance the learning ability of dominant crayfish.
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Petersen, Cecilia. "Paracrine regulation of Sertoli cell proliferation /." Stockholm, 2003. http://diss.kib.ki.se/2003/91-7349-443-7/.
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Demirel, Kars Meltem. "Molecular Mechanisms Of Vincristine And Paclitaxel Resistance In Mcf-7 Cell Line." Phd thesis, METU, 2008. http://etd.lib.metu.edu.tr/upload/3/12610241/index.pdf.
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Resistance to broad spectrum of chemotherapeutic agents in cancer cell lines and
tumors has been called multiple drug resistance (MDR). In this study, the molecular
mechanisms of resistance to two anticancer agents (paclitaxel and vincristine) in
mammary carcinoma cell line MCF-7 were investigated.
MCF-7 cells were selected in the presence of paclitaxel and vincristine by stepwise
dose increments. The cell viability and growth profiles of resistant sublines were
examined. As the resistance indices increased, the growth rates of sublines were
found to decrease. Gene and protein expression levels of the basic drug resistance
proteins P-gp and MRP1 were studied in sensitive and drug resistant MCF-7 cells. It
was shown that P-gp overexpression is significantly contributing to the developed
drug resistance phenotype.
Mutation analysis of beta tubulin gene which encodes the target of paclitaxel and
vincristine was performed. Single histidine to proline mutation was identified near
GTP binding site of beta tubulin in vincristine resistant subline which was not
reported before.
Apoptosis related BCL-2 and BAX were examined at both gene and protein
expression levels and they were not found to be significantly related to the developed
resistance in the sublines.
The reversal of drug resistance by various inhibitory agents of P-gp and MRP1 was
investigated by using flow cytometry. Synthetic silicon compounds were found to be
the most effective MDR reversal agents. The effects of various combinations of
anticancer drugs and reversal agents on cell proliferation were examined by
checkerboard microplate method. ALIS409-paclitaxel and paclitaxel-doxorubicin
pairs seem to have highest antiproliferative effects on resistant sublines.
The microarray expression profiling of sensitive and resistant MCF-7 cells was
performed for a much detailed and comprehensive analysis of drug resistance. The
results indicated that the upregulation of MDR1 gene is the dominating mechanism
of paclitaxel and vincristine drug resistance. Additionally up regulation of the genes
encoding the detoxifying enzymes (i.e. GSTP1) was observed. Significant down
regulation of apoptotic genes (i.e. PDCD2/4/6/8) and alterations in expression levels
of genes related to invasion and metastasis (MMPs, ADAMs, COL4A2, LAMA etc.)
were detected. Upregulation of some oncogenes (i.e. ETS, RAS) and cell cycle
regulatory genes (CDKN2A, CCNA2 etc.) was seen which may be in close relation to
MDR in breast cancer. Further studies will demonstrate the relationship between the
components contributing to drug resistance phenotype in breast cancer cells.
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Lin, Weiyang. "Phospholipid metabolism in the MCF-7 cell cycle, regulation of phosphatidylcholine accumulation." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape2/PQDD_0015/NQ53065.pdf.
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Reancharoen, Tharnkamol. "Ion transporting activities of an epithelial cell line, HCA-7 colony 30." Thesis, University of Cambridge, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.338258.
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Mohan, Bindu. "Role of Siglec-7 in ganglioside recognition and modulating NK cell biology." Thesis, University of Dundee, 2013. https://discovery.dundee.ac.uk/en/studentTheses/93d42a43-7c3c-4d6e-b69a-27cb4673c1db.
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Sialic acid binding Ig-like lectin-7 (Siglec-7), expressed primarily on NK cells, binds preferentially to alpha2,8 linked disialic acids such as present in the ganglioside GD3 that is upregulated in certain cancers. Siglec-7 is classified as an inhibitory receptor as it contains immunoreceptor tyrosine based inhibitory motifs. It has been shown to inhibit NK cytotoxicity in cellular assays thereby implying a role for it in NK cell mediated tumour surveillance. The aim of this project was to study factors affecting ligand recognition by Siglec-7 and its impact on NK cell functions. An investigation into the mechanism by which Siglec-7 mediates inhibitory signals to regulate NK cell biology was also carried out. Recognition of Siglec-7 for GD3 has been reported to be altered in the presence of complex gangliosides. This project was initiated with an aim to examine the role of such cis-interactions between GD3 and other gangliosides such as GM1 in biological systems and thereby its impact on NK cell biology. B16 (78) cell line was genetically modified to over-express both GD3 and GM1. This model system was then analysed using Siglec-7-Fc precomplexes for the recognition of GD3. Siglec-7-Fc binding of B16 (78) cells with high expression of GD3 and GM1 was significantly lower compared to cells having high expression of GD3 and low expression of GM1. However further investigation of these cis-interactions by confocal microscopy revealed that only less than 3% of the cells had patches of co-localization of the two gangliosides. Such lateral segregation of co-expressed GD3 and GM1 was also observed in another cell line model. Next, an investigation into the role of GD3 in modulating NK cell functions via Siglec-7 was carried out. Primary PBMCs and a Siglec-7 deficient NK cell line, NK92, were used for this purpose. The data obtained showed that Siglec-7 could negatively modulate NK cytotoxicity towards targets expressing disialylated ligands such as GD3. Furthermore Siglec-7 was also able to modulate integrin functions on NK cells. LFA-1 mediated adhesion of effectors to ICAM-1-Fc coated plates and the polarization of perforin granules to ICAM-1- Fc coated beads were negatively affected by the expression of Siglec-7 in the NK92 cell line. Biochemical analysis of LFA-1 mediated signalling in NK92 cells showed negative regulation of Src kinase activation, in an Siglec-7 dependent manner. Overall these findings suggest a role for Siglec-7 in modulating NK cell recognition of tumours with aberrant glycosylation patterns. They also form the basis of further investigation into the mechanisms of inhibitory signalling mediated by Siglec-7 and could therefore be of potential clinical relevance in NK cell mediated tumour clearance.
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Dias, Dos Santos Sheila. "Molecular mechanisms of early B cell differentiation : the role of Interleukin-7." Paris 6, 2005. http://www.theses.fr/2005PA066131.
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Liku, Muluye E. "CDK regulation of replication proteins: Mcm2-7 and DNA polymerase alpha primase." Diss., Search in ProQuest Dissertations & Theses. UC Only, 2008. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3324598.
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Baldursson, Baldur. "Development of squamous cell carcinoma in venous ulcers /." Stockholm, 2000. http://diss.kib.ki.se/2000/91-628-4079-7/.
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Björck, Erik. "Genetic studies of follicular and mantle cell lymphoma /." Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-347-7/.
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Darcansoy, Iseri Ozlem. "Investigation Of Docetaxel And Doxorubicin Resistance In Mcf-7 Breast Carcinoma Cell Line." Phd thesis, METU, 2009. http://etd.lib.metu.edu.tr/upload/3/12610422/index.pdf.
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Multidrug resistance phenotype of tumor cells describes resistance to wide range of structurally unrelated anticancer agents and is a serious limitation to effective chemotherapy. It is a multifactor yet not fully elucidated phenomenon by the involvement of diverse cellular pathways.
Aim of this study was to investigate the resistance mechanisms developed against docetaxel and doxorubicin that are widely used in the treatment of breast cancer in model cell line MCF-7. Resistant sublines were developed by application of drugs in dose increments and effect of docetaxel and doxorubicin on drug applied cells were investigated by cell viability assays. Expression analysis of P-gp, MRP1, BCRP, Bcl-2, Bax and &<br>#946<br>-tubulin isotypes were performed by RT-PCR, qPCR, Western blot and immunocytochemistry. Genome-wide expression analysis was also performed by cDNA microarray.
According to cell viability assays, drug applied cells developed varying degree of resistance to docetaxel and doxorubicin. Gene expression analysis demonstrated that de novo expression of P-gp contributed significantly to drug resistance. Expression levels of class II, III and V &<br>#946<br>-tubulin isotypes increased in docetaxel resistant sublines. According to microarray analysis, a variety of genes showed significantly altered expression levels particularly drug metabolizing and detoxification enzymes (i.e. increased GPX1 and GSTP1 with decreased POR), survival proteins (e.g. decreased TRAIL together with increased decoy receptors and CD40), extracellular matrix components (e.g. increased integrin signaling), growth factors and cytokines (e.g. EGFR1, FGFR1, CTGF, IL6, IL8 and IL18 overexpression), epithelial-mesenchymal transition proteins (i.e. increased vimentin and N-cadherin with decreased E-cadherin and occludin) and microtubule dynamics related proteins (e.g. increased MAP1B and decreased MAP7).
Development of cross-resistance and combined drug effects on resistant sublines were also studied. Results demonstrated that docetaxel and doxorubicin resistant cells developed cross-resistance to paclitaxel, vincristine, ATRA, tamoxifen and irradiation. Finally, modulatory effects of verapamil and promethazine in combined drug applications were investigated and verapamil and promethazine were shown to decrease MDR1 expression level thus reverse the MDR. They also showed synergic and additive effects in combined docetaxel and doxorubicin applications.
Identification of resistance mechanisms may personalize chemotherapy potentially increasing efficacy of chemotherapy and life quality of patients.
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Kaplan, Esra. "Development And Investigation Of Etoposide Resistance In Mcf-7 Breast Cancer Cell Line." Master's thesis, METU, 2010. http://etd.lib.metu.edu.tr/upload/12612781/index.pdf.
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Failure of chemotherapy in cancer patients because of development of drug resistance is a major problem. Alterations of DNA repair mechanisms and drug targets are among the important resistance mechanisms which are developed against topoisomerase II inhibitors etoposide and doxorubicin. Modifications in the expression levels of mismatch repair (MMR) genes due to resistance to topoisomerase II inhibitors are involved in breast cancer.
In this study, etoposide resistant sublines were developed from MCF7 breast cancer cell line (MCF7/S) and the expression levels of TOP2A and two important MMR genes MSH2 and MLH1 were examined by real time qPCR. Previously developed doxorubicin resistant cells were also studied for comparison. Etoposide resistant sublines MCF7/1000E, MCF7/1250E and MCF7/2000E were approximately 2, 3 and 4 fold resistant relative to parental MCF7/S cells, respectively. MLH1, MSH2 and TOP2A expressions decreased in both etoposide and doxorubicin resistant sublines relative to MCF7/S cells. Expression levels of TOP2A in resistant sublines differ between 10-95 percent of the expression levels in the parental cells. In the sublines MCF7/200E, MCF7/500E, MCF7/750E and MCF7/1000E a decrease in TOP2A gene expression was determined. In sublines MCF7/1250E and MCF7/2000E fluctuations in the expression levels were observed. Among the doxorubicin resistant sublines (MCF7/600D and MCF7/1000D), in MCF7/1000D which is more resistant to doxorubicin, TOP2A expression level was higher. Expression levels of MSH2 decreased regularly as the resistance increased. However, in MCF7/1250E significant increase relative to MCF7/1000E was observed. In MCF7/2000E, expression levels of MSH2 again significantly decreased to 41 percent of the levels in parental cell line. Expression levels of MLH1 decreased significantly (18-58 percent) in etoposide resistant sublines relative to MCF7/S cells. In doxorubicin resistant sublines, a decrease in MLH1 gene expression was observed in MCF7/1000D.
It can be concluded from the results that decrease in the expression levels of TOP2A, MSH2 and MLH1 genes may contribute to resistance together. Above a certain resistance level, sublines may develop new strategies for acquiring higher resistance. Whenever a strategy becomes limited, new strategies emerge. New approaches developed to overcome resistance in cancer chemotherapy should consider the molecular basis of resistance in different stages of the disease.
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Berrington, Mary. "Investigation of the role of chromosome 7 in human cell immortalisation and cancer." Thesis, University of Glasgow, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.301836.
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Aloufi, Nawaf. "The role of sCD127 in IL-7-Mediated T Cell Homeostasis in Vivo." Thesis, Université d'Ottawa / University of Ottawa, 2020. http://hdl.handle.net/10393/41089.
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Interleukin-7 is an essential cytokine that plays a major role in the development and homeostatic maintenance of T-cells. The presence of soluble forms of various cytokine receptors have been proposed to be involved in the endogenous regulation of cytokine activity. Due to the natural ability of soluble CD127 (sCD127) to bind to IL-7, there is an interest in its potential application as an immunotherapeutic agent in diseases, where IL-7 has been found to be relevant, including HIV infection. In this study, I hypothesize that by administering sCD127 to healthy mice, IL-7 activity should be enhanced, thus enhancing T cell proliferation in vivo.
The work presented here focuses on three main objectives: 1) evaluating the effect of IL-7 with or without sCD127 on T cell proliferation in healthy mice; 2) validating a mouse model of T cell depletion using anti-CD4 and CD8 antibodies; and 3) determining the effect of sCD127 treatment with or without IL-7 on T cell reconstitution and proliferation in the T cell depletion model. To assess the effect of administering exogenous sCD127, IL-7 or the combination on T cell proliferation, peripheral blood mononuclear cells and spleen were isolated, and stained to characterize T cell number, proliferation, and surface CD127 expression by flow cytometry. For the T cell depletion model, wild type C57BL/6 mice were injected intra-peritoneally with 150 μg single dose of anti-CD4 and anti-CD8 depleting antibodies. Consequently, mice were bled weekly to demonstrate the kinetics of T cell reconstitution following depletion (from d7 to d63).
Our results demonstrated that in healthy mice daily treatment with murine IL-7 significantly stimulated T cell proliferation and consequently increased cell number. This observation was further boosted by pre-complexing IL-7 with sCD127. For T cell depletion experiments, the kinetics of T-cell reconstitution was different between the CD4+ and CD8+ T cells. CD4+ T cell reconstitution was almost complete 6 weeks following T cell depletion, while CD8+ T cells were only partially reconstituted at this time point. Treatment with IL-7 or combined therapy had a transient and significant effect on T cell proliferation and reconstitution, and this influence was abrogated after treatment discontinuation. Interestingly, CD8+ T cells exert greater responses to our treatments in that a more pronounced proliferation and significant increase in cell number was observed relative to the effect seen on CD4+ T cells in both healthy and depleted mice.
In conclusion, antibody-mediated T cell depletion is a potentially valuable tool to investigate lymphopenia-induced proliferation and potential therapies thereof. This study suggests that combining sCD127 and IL-7 therapies enhances IL-7-mediated T cell proliferation, and provides important information for the potential therapeutic use of sCD127 and its impact on IL-7 function.
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Clark, Dawn Rachelle 1968. "Differential effects of Interleukin-7 on normal and HIV-modified T-cell development." Diss., The University of Arizona, 1996. http://hdl.handle.net/10150/282118.
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In this study, an organ culture chimera system was used to study the physiological role of Interleukin-7 (IL-7) in normal T cell development by antibody neutralization of cytokine activity. Additionally, the effect of IL-7 on HIV-modified T cell development was studied. When chimeras were treated with anti-IL-7 for 3 day intervals, a differential effect was observed. Early in culture, when the majority of the cells are CD4/CD8/CD3 triple negative (TN), anti-IL-7 decreased the number of immature and mature cells. The CD44⁺CD25⁺ TN cells were not able to make the transition to the CD44⁻CD25⁺ TN stage without IL-7. In contrast, when IL-7 is neutralized later in the culture period, when the majority of cells are in the double positive (DP) or mature single positive (SP) stages, the number of CD3⁺ cells increases. These data suggest that in addition to its capacity to maintain the viability of the immature cells, IL-7 may actually hold the cells in the immature state. It has been suggested that HIV infection affects the ability to regenerate new T cells. Peripheral blood mononuclear cells (PBMC) from HIV-infected patients and uninfected controls were used as donor cells. The number of mature CD4, CD8 and CD4/8 double positive (DP) cells generated in the cultures derived from HIV-infected PBMC was diminished. This lack of development occurred even with blood from donors with a CD4 count of 1,000/μL. Limit dilution experiments showed that the number of functional precursors in HIV-infected patients is lower than in uninfected patients. The CD3⁻ CD8⁺ and DP T cells were not reduced unless the CD4 count was <250/ml. These data suggest that there is a block in T cell development at the DP stage in cultures derived from PBMC with CD4 counts. IL-7 treatment resulted in a greater loss in the number of T cells produced by infected PBMC. These data show that while IL-7 plays a critical role in normal T cell development, it has the potential to increase the T cell depletion of HIV-infected individuals.
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Barra, Melanie Marianne [Verfasser], and Markus [Akademischer Betreuer] Feuerer. "Transcription factor 7 limits regulatory T cell generation and influences peripheral T cell subsets / Melanie Marianne Barra ; Betreuer: Markus Feuerer." Heidelberg : Universitätsbibliothek Heidelberg, 2014. http://d-nb.info/1180735056/34.
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Dujardin, Hélène. "Ontogeny and homeostasis of the peripheral regulatory CD4T cell compartment." Paris 6, 2006. http://www.theses.fr/2006PA066109.
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Woll, Addison Wayne. "Role of PPAR[gamma] and retinol binding protein 7 in the vascular endothelium." Thesis, University of Iowa, 2017. https://ir.uiowa.edu/etd/6013.
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Peroxisome Proliferator-Activated Receptors (PPARs) are a family of conserved ligand activated nuclear receptor transcription factors heterogeneously expressed in mammalian tissues. PPARγ is recognized as a master regulator of adipogenesis, fatty acid metabolism, and glucose homeostasis, but genetic evidence also supports the concept that PPARγ regulates the cardiovascular system, particularly vascular function and blood pressure. There is now compelling evidence that the beneficial blood pressure lowering effects of PPARγ activation are due to its activity in vascular smooth muscle and endothelium, through its modulation of nitric oxide-dependent vasomotor function. Endothelial PPARγ regulates the production and bioavailability of nitric oxide, while PPARγ in the smooth muscle regulates the vasomotor response to nitric oxide. We recently identified retinol binding protein 7 (RBP7) as a PPARγ target gene that is specifically and selectively expressed in the endothelium. We will discuss the evidence that RBP7 is required to mediate the antioxidant effects of PPARγand mediate PPARγ target gene selectivity in the endothelium, as well as the work so far in determining the mechanism of RBP7:PPARγ interaction. (56)
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Sener, Emine Cigdem. "Reversal Of Paclitaxel Resistance In Mcf-7 Cell Line By A Chemical Modulator Elacridar." Master's thesis, METU, 2012. http://etd.lib.metu.edu.tr/upload/12614644/index.pdf.
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The phenomenon called multi drug resistance (MDR) is the resistance of cancer cells to anticancer drugs before or during chemotherapy. One of the mechanisms causing MDR is the upregulation of efflux pumps. The overexpression of MDR1 and MRP1 results in increased efflux of anticancer agents.
The aim of this study was to reverse MDR1-mediated paclitaxel resistance in MCF7 breast cancer cell line by a chemical MDR modulator elacridar. In this study, cytotoxicity and the reversal effect of elacridar on sensitive and paclitaxel resistant cells were investigated. The effect of elacridar on MDR1 and MRP1 gene expressions were also determined.
Results indicated MDR1 gene was highly overexpressed (208 fold) in MCF7/Pac cells compared to MCF7/S cells. Elacridar was not found to be cytotoxic in MCF7/Pac cells up to 30µ<br>M. XTT results demonstrated 0.5µ<br>M elacridar
concentration was able to restore the antiproliferative effect of paclitaxel by 94% in MCF7/Pac cells. Complete MDR reversal was achieved at 5µ<br>M elacridar concentration. qPCR results revealed dose dependent upregulations in MDR1 and MRP1 gene expression levels after elacridar treatment which did not prevent reversal of MDR by elacridar.
Elacridar was shown to be very effective against paclitaxel resistance in MCF7/Pac cells at low concentrations. Therefore, it can be a suitable candidate for therapeutic applications in patients who developed paclitaxel resistance. Nevertheless, dose dependent upregulations in MDR1 and MRP1 gene expressions should be taken into consideration and overdose elacridar administration should be avoided.
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Marsh, Katrina Anne. "Characterisation of subpopulations isolated from HCA-7, a heterogenous human colonic carcinoma cell line." Thesis, Imperial College London, 1990. http://hdl.handle.net/10044/1/46434.
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Rajamanoharan, Dayani. "Investigating calcium binding protein 7 (CaBP7), phosphoinositide signalling and lysosomes during mammalian cell mitosis." Thesis, University of Liverpool, 2015. http://livrepository.liverpool.ac.uk/2044661/.
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Calcium binding proteins (CaBPs) are a subfamily of the calmodulin related superfamily of EF hand containing proteins. CaBPs can be further divided into two subgroups (CaBPs 1-5 and CaBP7 and 8) due to differing cation binding properties and because CaBP7 and 8 have a distinct trans- membrane domain at the C-terminal that is essential for determining their subcellular location. CaBP7 and 8 have been shown to interact with Golgi resident Phosphatidylinositol 4-Kinase-IIIbeta (PI4KIIIβ) and to be involved in calcium (Ca2+) regulated Golgi to plasma membrane trafficking pathway. At resting Ca2+ levels CaBP7 and 8 interact with PI4KIIIβ and inhibit its enzymatic function, to prevent phosphatidylinositol 4-phosphate (PI4P) synthesis and vesicular trafficking. At high Ca2+ levels another Golgi resident Ca2+-binding protein, neuronal calcium sensor-1 (NCS-1), displaces CaBP7 and 8 from PI4KIIIβ, stimulating PI4P production and thereby coupling local Ca2+ signals to vesicular transport. In addition to this documented trafficking function, a high- throughput RNAi screen identified CaBP7 as an essential factor for successful completion of cytokinesis in HeLa cells. Mitotic cell division is a fundamental biological process required for normal cellular growth, development and aging. Mitotic failure can lead to a state of aneuploidy, which is an accepted driver of cellular transformation and tumorigenesis. Therefore, this thesis specifically focused on CaBP7 with an aim to understand its unique role during mammalian cell mitosis. When the subcellular localisation of CaBP7 was examined it was found to be present on both the Golgi complex and, unexpectedly, lysosomes. A recent study identified a previously uncharacterised lysosomal pool of PI4KIIIβ, ! i! cellular depletion of which disrupted lysosome trafficking and ultimately led to distinctive lysosomal clustering. In an effort to connect these findings, analyses were designed to reveal whether CaBP7 was involved in regulation lysosomal PI4KIIIβ. CaBP7 overexpression (inhibition of PI4KIIIβ) increased clustering of lysosomes in a similar manner to that observed on cellular depletion of PI4KIIIβ. This result provides evidence to suggest a role for CaBP7 in lysosomal PI4KIIIβ regulation and lysosome trafficking, which will require further research to fully delineate. In order to further understand CaBP7 involvement in mitosis, CaBP7 was depleted from cells using shRNAi, which resulted in a 3-fold increase in binucleate cells compared to control cells. Binucleate cells form as a direct consequence of cytokinesis failure implying a functional requirement for CaBP7 during this process. This data replicated findings from the previous large scale RNAi screen and was extended upon significantly in this study through an analysis of a range of PI4KIIIβ effectors and their influence on mitosis. The same binucleate phenotype was observed with PI4KIIIβ overexpression suggesting a role for CaBP7 in regulating PI4KIIIβ during cytokinesis. Localisation studies revealed that CaBP7, PI4KIIIβ and lysosomes re-distributed together extensively during mitosis implying a link between all three in this process. In particular, at cytokinesis, all three components were localised in discrete clumps flanking either side of the nucleus. Intriguingly this marked re-distribution was lost upon CaBP7 depletion, possibly revealing a mechanistic link to cytokinesis failure. Collectively, data acquired regarding CaBP7, PI4KIIIβ and lysosomes inferred a role for lysosome positioning during mitosis and to test this ! ii! hypothesis experiments were designed to examine a requirement for specific lysosomal activities during cytokinesis. Lysosomes have emerged as Ca2+ signalling platforms and this function was assessed using novel genetically encoded Ca2+ sensors targeted specifically to these organelles. No Ca2+ signals originating from lysosomes during mitotic cell division were detected in these analyses. The other known functions of lysosomes were also examined in these studies. Inhibition of lysosomal catabolism failed to influence mitosis however disruption of lysosomal membrane fusion with the agents GPN and vacuolin-1 induced a significant increase of binucleate cell numbers. Collectively these functional assays suggest a potential requirement for lysosomal membrane fusion during cytokinesis, which would be consistent with a documented function for endosomes during this process. This thesis provides new insights into the role of a Ca2+ binding proteins, phosphoinositide signalling and, uniquely, lysosomal compartments, during mammalian cell mitosis. It describes an outline for a potentially new regulatory input into mitosis and provides a platform for future detailed examinations of the mechanistic links between CaBP7, lysosomes, lysosomal PI4KIIIβ activity and PI4P levels during normal cytokinesis in mammalian cells.
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Vasam, Goutham. "Angiotensin-(1-7): A Target for Stem Cell Mobilopathy and Vascular Repair in Diabetes." Diss., North Dakota State University, 2017. https://hdl.handle.net/10365/28144.
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Bone marrow stem/progenitor cells (BMPCs) accelerate vascular repair by re-endothelialization and revascularization of ischemic areas. Diabetes causes impairment of BMPC mobilization, a.k.a. stem cell mobilopathy, and reparative functions, which have now been considered as a major contributing factor for the development of macro and microvascular complications and end-organ damage. Therefore, autologous cell therapies for the treatment of diabetic vascular complications are currently not possible. In this study, I tested the effects of Angiotensin (Ang)-(1-7), a heptapeptide member of the protective arm of renin-angiotensin system, on mobilization of BMPCs and their ischemic vascular repair functions that are impaired in diabetes. Streptozotocin-induced diabetic or db/db mice were used. Circulating and bone marrow Lineage- Sca1+ c-Kit+ (LSK) cells were decreased in diabetes, which was normalized by Ang-(1-7). Ang-(1-7) specifically increases Rho-kinase (ROCK) activity in diabetic bone marrow (BM) LSK cells, and fasudil, a ROCK inhibitor, prevented the beneficial effects of Ang-(1-7). BM Slit3 levels were increased by Ang-(1-7), which might have activated ROCK in LSK cells and sensitized for stromal-derived factor-1? (SDF)-induced migration. In relation to ischemia, diabetes prevented LSK cell mobilization and blood flow recovery, which were reversed by Ang-(1-7). Ang-(1-7), in combination with G-CSF or plerixafor reversed the stem cell mobilopathy in diabetes. These beneficial effects of Ang-(1-7) were blunted in Mas receptor knockout (MasR-KO) mice. These results suggest that MasR is a promising target for the treatment of diabetic bone marrow mobilopathy and vascular disease. Overall, this study provided strong preclinical evidence, supporting Ang-(1-7) as a promising molecule for the treatment of diabetic stem cell mobilopathy and vascular disease.<br>American Heart Association (13SDG16960025)<br>COBRE Pilot Project Grant (Intramural)<br>Center for Protease Research (P30 GM103332 ? 01).
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Korfali, Nadia. "Genetic analysis of caspase-6 and caspase-7 function in vertebrate DT40 cell line." Thesis, University of Edinburgh, 2003. http://hdl.handle.net/1842/11011.
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Apoptosis, also known as programmed cell death, is an evolutionarily conserved mechanism by which the organism removes unwanted cells. The process is common to somatic as well as germ cells. It is actively involved in development and morphogenesis, cell number control and removal of infected, mutated or damaged cells. Many insights on the activation of final triggers and pathways in apoptosis came from genetic studies of apoptosis using the worm, C.elegans This work showed that the worm Ced-3 is a protease of pivotal role in apoptosis of C.elegans. The mammalian counterparts of CED-3 have been identified as members of a family of intracellular proteases that form the core of the apoptotic machinery. Since these are cysteine proteases that cleave cellular substrates at specific aspartate residues, they were all termed caspases. In the last ten years natural and synthetic inhibitors and genetic approaches have been used to study elucidate specific caspase function. An alternative system is gene disruption in the chicken DT40 cell line. These cells have a high homologous recombination rate that facilitates the isolation of knockout alleles. The aim of my project is the genetic analysis of caspase-6 and -7 function. My work started with an ongoing caspase-6 knockout project along with a senior postdoctoral scientist in our lab, Dr Sandrine Ruchaud. Subsequently, I concentrated my work on the caspase-7 knockout poject. I generated DT40 cell line where both alleles of caspase-6 and -7 were disrupted independently. Caspase-6: No obvious morphological differences were observed in the apoptotic process in caspase-6 deficient cells compared to the wild type. However, examination of apoptosis in a cell free system revealed a block in chromatin condensation and apoptotic body formation when nuclei from HeLa cells expressing lamin A or lamin A-transfected Jurkat cells were incubated in caspase-6 deficient apoptotic extracts. Transfection of exogenous caspase-6 into the clone reversed this phenotype. Lamins A and C, which are caspase-6-only substrates, were cleaved by the wild type and heterozygous apoptotic extracts but not by the extracts lacking caspase-6. Furthermore, the caspase-6 inhibitor zVEID-fmk mimicked the effects of caspase-6 deficiency and prevented the cleavage of lamin A. Taken together these observations indicate that caspase-6 activity is essential for lamin A cleavage and that when lamin A is present, it must be cleaved in order for the chromosomal DNA to undergo complete condensation during apoptotic execution. Caspase-7: Viability assays showed that caspase-7' clones are more resistant to common apoptosis-inducing drugs such as etoposide and staurosporine. Further examination of the apoptotic process revealed that caspase-7 cells show a delay in phosphatidylserine externalization and DNA fragmentation as well as cleavage of the caspase substrates PARP and lamins BI and B2. Caspase affinity labeling and activity assays indicated that deficient cells exhibit a delay in caspase activation when compared to wild type DT40 cells, providing an explanation for the differences in apoptotic execution between caspase-7 null and wild type DT40 cells. These results strongly suggest that caspase-7 is involved earlier than other effector caspases in the apoptotic execution process in DT40 B lymphocytes. My results have provided important new insights into the function of caspase-6 and caspase-7 during apoptotic execution.
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Tiger, Carl-Fredrik. "Cellular Interactions with Extracellular Matrix During Development and in Muscle Disease." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis, 2002. http://publications.uu.se/theses/91-554-5328-7/.
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Neumann, Chase K. A. "Phosphatidylinositol Remodeling through Membrane Bound O-acyl Transferase Domain-7 (MBOAT7) Promotes the Progression of Clear Cell Renal Cell Carcinoma (ccRCC)." Case Western Reserve University School of Graduate Studies / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=case1586250046745924.
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O'Brien, Kevin P. "The role of PDGFB in dermatofibrosarcoma protuberans and giant cell fibroblastoma /." Stockholm, 2000. http://diss.kib.ki.se/2000/91-628-4017-7/.
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Hayes, Sandra C. "Exercise, functional capacity and quality of life in peripheral blood stem cell transplant patients." Thesis, Queensland University of Technology, 2001. https://eprints.qut.edu.au/36758/7/36758_Digitised%20Thesis.pdf.
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Sakalli, Elif. "Comparative Effects Of Emodin On Biological Activities Of Mcf-7 And Mda-231 Cell Lines." Master's thesis, METU, 2010. http://etd.lib.metu.edu.tr/upload/12612825/index.pdf.
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Emodin (1,3,8-trihydroxy-6-methylanthraquinone) is a phytoestrogenic component of Rheum plant extracts which has been used for medical treatment since ancient times. It has been shown to have anti-inflammatory and anti-cancer effects. In our research, we aimed to study the biological effects of emodin on MCF-7 and MDA-231 cell lines.
Cytotoxicity assays showed that emodin treatment for 48hours caused a concentration dependent decrease in viable cell numbers of both cell lines. As determined by cell counting with tryphan blue, IC50 values were 8.40 and 12.17 µ<br>g/ml for MCF-7 and MDA-231 cells, respectively.
Apoptotic effects of emodin was investigated by measuring the changes in apoptotic and antiapoptotic gene expressions by qRT-PCR. In MCF-7 cells, Bax expression increased with increasing emodin concentrations, while Bcl-2 expression was downregulated. Bax/Bcl-2 ratio was calculated as 9.2 fold at 10µ<br>g emodin/ml treatment for 48 hours, indicating stimulation of apoptosis. However, Bax/Bcl-2 ratio was found 1.6 fold for MDA-231 cells. These results were in accordance with the results obtained from microarray analysis of related gene expressions. MCF-7 cells were more apoptotic in comparison to MDA-231 cells. DNA fragmentation was observed in MCF-7 cells by TUNEL method.
GST enzyme activity that was measured using CDNB as substrate, was increased 100% with respect to control up to 5µ<br>g emodin/ml treatment of MCF-7 cells for 48 hours. However, effect of emodin on GST activity in MDA-231 cells was found insignificant. According to microarray analysis results, emodin affected the gene expressions of GST isozymes in MCF-7 cells much more than in MDA-231 cells.
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Legendre, Christophe. "Identification of a leu-7+leu-3+ cell subset in long-term renal allotransplant recipients." Thesis, McGill University, 1986. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=65388.
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Chan, Wai-long, and 陳慧朗. "The protective role of bone morphogenetic protein-7 against mesangial cell injury in IgA nephropathy." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2008. http://hub.hku.hk/bib/B41290872.
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Chan, Wai-long. "The protective role of bone morphogenetic protein-7 against mesangial cell injury in IgA nephropathy." Click to view the E-thesis via HKUTO, 2008. http://sunzi.lib.hku.hk/hkuto/record/B41290872.
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Pfeiffer, Thomas J. "Phytoestrogens may inhibit proliferation of MCF-7 cells, an estrogen-responsive breast adenocarcinoma cell line." Link to electronic thesis, 2004. http://www.wpi.edu/Pubs/ETD/Available/etd-0430104-132238.
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Reynolds, Joseph Benjamin. "Mathematical models of the roles of IL-2 and IL-7 in T cell homeostasis." Thesis, University of Leeds, 2014. http://etheses.whiterose.ac.uk/6832/.
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We study the homeostasis of a peripheral naive T cell population through the use of deterministic mathematical models. A two compartment approach is used, where, naive T cells are assumed to be either in a resting state, or undergoing the cell cycle. We begin by assuming all rates are linear, then discuss the limitations in doing so. We next explore examples of published methods which improve this simple description. Finally, we introduce a model in which resting T cell survival and entry into the cell cycle is assumed to be dependent on the amount of available IL-7. To aid our description of T cell homeostasis, a stochastic model of IL-7 signalling is developed. In this model we consider the number of IL-7 receptors, either membrane bound or internalised, the extra-cellular concentration of IL-7, and the amount of IL-7 induced signalling. The model is used to derive a relationship between the amount of IL-7 induced signalling to the extra-cellular concentration of IL-7. The survival and proliferative ability of the T cell population is then assumed to be dependent on the amount of IL-7 induced signalling with respect to IL-7 signalling thresholds for survival and division. This signalling relation is then used with the model of T cell homeostasis. The model is fitted to experimental data measuring the expansion of transgenic naive T cells in lymphopenic mice. We show this approach can capture the homeostatic equilibrium, and notably, time scales required to reach equilibrium. The model is then explored in the context of the human periphery. In a separate piece of work we develop a stochastic Markov model of the peripheral CD4+ T cell pool, in which we consider sub-populations of naive, IL-2 producing, IL-2 non-producing and regulatory T cells. The balance between the IL-2 producing and regulatory sub-populations is assumed to be determined by a recently proposed quorum-sensing hypothesis. This model is explored in scenarios where no antigen is presented to the CD4+ population, before and after a challenge, and when antigen is presented at a constant level. We show, amongst other results, that the number of regulatory T cells in equilibrium is greater when antigen is presented, whilst the number of IL-2 producing T cells remains the same. We finally use the stochastic aspect of this model to explore probabilities of and times to extinction of the sub-populations.
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Sasson, Sarah Christina National Centre in HIV Epidemiology & Clinical Research Faculty of Medicine UNSW. "Dysregulation of the IL-7/IL-7R system: implications for T-cell homeostasis in HIV-1 infection and pre-B cell oncogenesis." Awarded by:University of New South Wales. National Centre in HIV Epidemiology & Clinical Research, 2009. http://handle.unsw.edu.au/1959.4/44521.
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Interleukin (IL-)7 acts via its receptor (lL-7R) which consists of a specific a-chain (CD127) dimerised to the common y-chain (CD 132). IL-7R signalling triggers survival and proliferation and plays a central role in T-cell homeostasis, however it's role in B-cell biology remains unclear as does the post ligand-binding fate ofCD127 and CD132. IL???7 and IL-7R expression on T-cells was examined in different phases of HIV???) infection using ELlSA and flow-cytometry. Novel populations of T-cells based on lL-7R expression were further characterised by flow-cytometry, sjTREC and an HIV-DNA assay. Expression of IL-7R was screened for on a large number of B-cell derived cancers from both HIV-l infected and uninfected hosts, and plasma levels of IL-7 and a number of other cytokines was also measured in these patients by ELlSA or bead array. The effects of exogenous IL-7 on surface COl27 were studied in vitro in B- and T-Iineage cells. A COS-I cellular model of IL-7induced internalisation of CD127 and CD132 using fluorescent and biochemically tagged species was also developed and internalised proteins were studied by epifluorescence microscopy and western blot. Plasma IL-7 was up-regulated early in primary HIV infection and further so in chronic HIV infection. Elevations of plasma IL-7 inversely correlated with absolute C04+ T-cell count and loss of surface CO127 expression on T-cells. Specifically there was a net loss of COI27+132- and gain in COI27-132+ CD4+ and C08+ T-cells. The COI27+132- T-cells depleted in HIV infection were a subset ofsjTREC-rich naive T-cells that were Ki-67-Bc1-2high. During HIV-1 infection there was an expansion of more activated CDI27+132+ and CD127132+T-cells the latter being enriched for T(E)M and tenninally differentiated T-cells that were Ki-67+BcI-2low and contained high amounts of HIV-ONA. Additionally, we found evidence of CO127 expression on pre-B-acute lymphoblastic leukaemia cells in HIV???uninfected patients which was associated with a Ki-67+Bcl-2high phenotype. Normal pre-B and leukemic cells did not undergo IL-7 induced down-regulation of COl27 to the same extend as T-lineage cells, suggesting distinct regulatory mechanisms. Finally our cellular model showed IL-7 induced internalisation of both CDI27 and CDl32 into Iysosomes within 2h in a Clathrin dependent process. Internalisation of both COl27 and CD132 from the plasma membrane was further confirmed by reversible biotinylation studies and western bIoI. Dysregulation of the IL-7I1L-7R axis contributes to altered T-cell homeostasis in HIV-1 infection and to pre-B-ALL oncogenesis. Further investigations of this pivotal cytokine system are warranted.
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Stavropoulou, Vaia. "Role of tripeptidyl peptidase II in cell cycle regulation and tumor progression /." Stockholm, 2006. http://diss.kib.ki.se/2006/91-7140-851-7/.
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Ekholm-Reed, Susanna. "The role of cyclin E in cell cycle regulation and genomic instability /." Stockholm, 2004. http://diss.kib.ki.se/2004/91-7349-894-7/.
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Fernandez, Victor. "Variant antigens at the infected red cell surface in Plasmodium falciparum malaria /." Stockholm : [Karolinska institutets bibl.], 2001. http://diss.kib.ki.se/2001/91-628-4891-7/.
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Supornsilchai, Vichit. "Effects of endocrine disruptors on adrenocortical and leydig cell steroidogenesis /." Stockholm : Karolinska institutet, 2007. http://diss.kib.ki.se/2007/978-91-7357-276-7/.
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