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Dissertations / Theses on the topic 'PI3K TARGET'

Author: Grafiati

Published: 11 September 2023

Last updated: 31 July 2025

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1

Stamatkin, Christopher W. "PHOSPHATIDYLINOSITOL 3-KINASE (PI3K) AS A THERAPEUTIC TARGET IN NSCLC." UKnowledge, 2014. http://uknowledge.uky.edu/pharmacy_etds/58.

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Deregulated activation of phosphatidylinositol 3-kinase (PI3K) pathway is central to many human malignancies. The functions of this pathway are critical for normal cell metabolism, proliferation, and survival. In lung cancers, the PI3K pathway activity is often aberrantly driven by multiple mutations, including EGFR, KRAS, and PIK3CA. Molecules targeting the PI3K pathway are intensely investigated as potential anti-cancer agents. Although inhibitors of the pathway are currently in clinical trials, rational and targeted use of these compounds, alone or in combination, requires an understanding

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2

McCarragher, Leeza Sarah Marie. "PI3K signalling blockade : a target for chemotherapeutic enhancement in breast cancer." Thesis, University of Sheffield, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.401117.

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Cerovac, Vesna. "Studies on the PI3K/mTOR pathway as cytostatic treatment target in pituitary adenomas." Diss., lmu, 2010. http://nbn-resolving.de/urn:nbn:de:bvb:19-119322.

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ULTIMO, Simona. "Inhibition of the PI3K/Akt/mTOR signaling pathway as a therapeutic target for Acute Lymphoblastic Leukemia." Doctoral thesis, Università degli studi di Ferrara, 2018. http://hdl.handle.net/11392/2487845.

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Acute Lymphoblastic Leukemia (ALL) is a malignant disorder characterized by the abnormal clonal proliferation of B-cell progenitors (B-ALL) or immature stage thymocytes (T-ALL). Constitutive activation of the PI3K/Akt/mTOR network is a common feature of B- and T-ALL, influencing cell growth and survival. The PI3K/Akt/mTOR inhibitors are currently being developed for clinical use either as single agents or in combination with conventional chemotherapy for T-ALL patient treatment. In this study it has been investigated the effects of a panel of PI3K/Akt/mTOR inhibitors on healthy human CD4+ T-c

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DARICI, SALIHA NUR. "LEUCEMIA MIELOIDE ACUTA CON MUTAZIONE FLT3-ITD: razionale per l'uso combinato di inibitori di fosfoinositide 3-chinasi e recettori tirosin chinasici." Doctoral thesis, Università degli studi di Modena e Reggio Emilia, 2022. http://hdl.handle.net/11380/1278342.

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In Europa, la sopravvivenza a 5 anni dei pazienti affetti da leucemia mieloide acuta (LMA) è solo del 20%. La duplicazione interna in tandem del gene FLT3 (FLT3-ITD), che codifica per il recettore della tirosina chinasi FLT3, è la mutazione più frequente (~ 25%) nella LMA con cariotipo normale, dove porta all'attivazione costitutiva della chinasi FLT3. Nonostante risultati iniziali molto promettenti con inibitori di FLT3 (FLT3i) nei pazienti con questa mutazione, pochi pazienti hanno remissioni prolungate, evidenziando la necessità di nuove e più efficaci terapie. La persistenza delle cellule

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6

Lonetti, Annalisa <1982&gt. "Study of PI3K/Akt signaling pathway as potential molecular target for T-cell acute lymphoblastic leukemia (T-ALL) treatment: pan-inhibition of PI3K catalitic isoforms as better therapeutic approach." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2015. http://amsdottorato.unibo.it/6763/1/Annalisa_Lonetti_tesi.pdf.

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Class I phosphatidylinositol 3-kinases (PI3Ks) are heterodimeric lipid kinases consisting of a regulatory subunit and one of four catalytic subunits (p110α, p110β, p110γ or p110δ). p110γ/p110δ PI3Ks are highly enriched in leukocytes. In general, PI3Ks regulate a variety of cellular processes including cell proliferation, survival and metabolism, by generating the second messenger phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3). Their activity is tightly regulated by the phosphatase and tensin homolog (PTEN) lipid phosphatase. PI3Ks are widely implicated in human cancers, and in part

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Lonetti, Annalisa <1982&gt. "Study of PI3K/Akt signaling pathway as potential molecular target for T-cell acute lymphoblastic leukemia (T-ALL) treatment: pan-inhibition of PI3K catalitic isoforms as better therapeutic approach." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2015. http://amsdottorato.unibo.it/6763/.

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Class I phosphatidylinositol 3-kinases (PI3Ks) are heterodimeric lipid kinases consisting of a regulatory subunit and one of four catalytic subunits (p110α, p110β, p110γ or p110δ). p110γ/p110δ PI3Ks are highly enriched in leukocytes. In general, PI3Ks regulate a variety of cellular processes including cell proliferation, survival and metabolism, by generating the second messenger phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3). Their activity is tightly regulated by the phosphatase and tensin homolog (PTEN) lipid phosphatase. PI3Ks are widely implicated in human cancers, and in part

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8

Venugopal, Smrruthi Vaidegi. "Differential Roles of Mammalian Target of Rapamycin Complexes 1 and 2 in Migration of Prostate Cancer Cells." DigitalCommons@Robert W. Woodruff Library, Atlanta University Center, 2019. http://digitalcommons.auctr.edu/cauetds/189.

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In this study, we investigated differential activation and the role of two mTOR complexes in cell migration of prostate cancer cells. Specific knock-down of endogenous RAPTOR and RICTOR by siRNA resulted in decreased cell migration in LNCaP, DU145, and PC3 cells indicating that both mTORC1 and mTORC2 are required for cell migration. EGF treatment induced the activation of both mTORC1 and mTORC2 as determined by complex-specific phosphorylation of mTOR protein. Specific knock-down or inhibition of Rac1 activity in PC3 cells blocked EGF-induced activation of mTORC2, but had no effect on mTORC1 a

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9

Stellwagen, Florian [Verfasser], Jürgen E. [Akademischer Betreuer] Gschwend, Angela [Akademischer Betreuer] Krackhardt, and Margitta [Akademischer Betreuer] Retz. "Bedeutung des PI3K/mTOR Signalweges als Ziel einer Target- Therapie im Harnblasenkarzinom / Florian Stellwagen. Gutachter: Jürgen E. Gschwend ; Angela Krackhardt ; Margitta Retz. Betreuer: Jürgen E. Gschwend." München : Universitätsbibliothek der TU München, 2013. http://d-nb.info/104718530X/34.

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10

Geng, Xinyan. "Investigations into how best to target FGFR2 mutant endometrial cancer." Thesis, Queensland University of Technology, 2017. https://eprints.qut.edu.au/123437/1/Xinyan%20Geng%20Thesis.pdf.

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Endometrial cancer (EC) is the fourth most common cancer in women in developed countries, such as North America, Europe and Australia. Patients with low-grade, early-stage disease usually have a favourable survival rate. However, patients that present at an advanced stage of disease have an average survival of only 12 months. Current treatments for these patients are radiation and chemotherapy, which offer limited clinical benefit. There is no efficient treatment for advanced EC. Improved therapeutic approaches are needed for the treatment of recurrent and metastatic endometrial cancer. Recent

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11

Sears, Daniel. "Identification of PI3K/Akt targets in chronic myeloid leukaemia." Thesis, Imperial College London, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.505451.

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12

Rowling, Emily. "Pre-clinical evaluation of novel anti-metastatic targets." Thesis, University of Manchester, 2014. https://www.research.manchester.ac.uk/portal/en/theses/preclinical-evaluation-of-novel-antimetastatic-targets(caa9ab41-c054-4559-b575-3fd8974005a7).html.

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Background: Radiotherapy is used in the treatment of over 50% of cancer patients and bar surgery, is the most effective cancer intervention. However, in the clinic secondary malignancies have been observed following radiotherapy and in vitro increased cell migration and invasion have been seen following radiation. The Src/FAK signalling pathway is known to play an important role in the metastatic phenotype through its involvement in cell adhesion, migration and invasion and we have previously demonstrated that radiotherapy can activate this pathway along with the phosphoinositide 3-kinase (PI3

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Farghaly, Hanan. "Pharmacological targets for gene therapy in lung inflammation." Thesis, University of Bath, 2008. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.500756.

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Interleukin-13 (IL-13) has been implicated as a critical inducer of a number of features of allergy and asthma including the induction of nonspecific airway hyperresponsiveness (AHR), eosinophilic inflammatory response, eotaxin production, excess mucus formation, and fibrosis. Determining the mechanism(s) of AHR, a hallmark of asthma, is crucial to our understanding of both the pathogenesis and successful treatment of asthma. After carrying out initial experiments to determine the effect of IL-13-induced AHR on murine and rat tracheal rings, mice tissues were chosen for subsequent experiments

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Chen, Yu-Ting. "Dissection of the PI3K/Akt/mTOR pathway identifies potential therapeutic targets in canine tumours." Thesis, University of Edinburgh, 2013. http://hdl.handle.net/1842/8075.

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Introduction: Over the past decades, considerable advances in understanding of cell biology at genetic, epigenetic and proteomic levels led to development of new strategies for better outcome of cancer therapy. One of these new strategies is targeting the class I PI3K/Akt/mTOR signaling pathway, in that this pathway plays a key role in regulation of many cellular functions, including proliferation, survival, metabolism, autophagy and motility. Dysregulation of the class I PI3K/Akt/mTOR pathway has been documented in a variety of human tumours and inhibition of this pathway has been observed to

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15

Jonasson, Jennifer. "Analysis of PIK3CA mutations in tumours from patients with non-small cell lung cancer using pyrosequencing." Thesis, Uppsala universitet, Institutionen för kvinnors och barns hälsa, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-227762.

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A subgroup of non-small cell lung cancer (NSCLC) cases harbour mutations in classical oncogenes, which can affect therapy response and prognosis. By therapeutically targeting the corresponding proteins with inhibitory drugs, the clinical outcome for these lung cancer patients may be improved. One of these oncogenes is the phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) which encodes the catalytic subunit of the phosphatidylinositol 3 kinase (PI3K). PIK3CA is a central regulator in the PI3K/Akt/mTOR pathway, which controls cell growth and apoptosis. Mutations in

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16

Pridham, Kevin James. "Investigating Novel Targets to Inhibit Cancer Cell Survival." Diss., Virginia Tech, 2004. http://hdl.handle.net/10919/82855.

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Cancer remains the second leading cause of death in the United States and the world, despite years of research and the development of different treatments. One reason for this is cancer cells are able to survive through adaptation to their environment and aberrantly activated growth signaling. As such, developing new therapies that overcome these hurdles are necessary to combat cancer. Previous work in our laboratory using RNA interference screening identified genes that regulate the survival of glioblastoma (GBM) or autophagy in chronic myelogenous leukemia (CML) cancer cells. One screen iden

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Pridham, Kevin J. "Investigating Novel Targets to Inhibit Cancer Cell Survival." Diss., Virginia Tech, 2018. http://hdl.handle.net/10919/82855.

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Cancer remains the second leading cause of death in the United States and the world, despite years of research and the development of different treatments. One reason for this is cancer cells are able to survive through adaptation to their environment and aberrantly activated growth signaling. As such, developing new therapies that overcome these hurdles are necessary to combat cancer. Previous work in our laboratory using RNA interference screening identified genes that regulate the survival of glioblastoma (GBM) or autophagy in chronic myelogenous leukemia (CML) cancer cells. One screen iden

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Qin, Qizhi. "Evaluation of the therapeutic potential of Akt inhibition in a translational model of histiocytic sarcoma." Diss., Virginia Tech, 2018. http://hdl.handle.net/10919/97520.

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Histiocytic sarcoma (HS) is an exceptionally rare malignant neoplasm derived from dendritic cells and histiocytes, with no available effective treatment options. Akt signaling and proteasome dysfunction have been implicated in the pathogenesis of the disease, both in humans and dogs. Our work aims to investigate the importance of the Akt signaling pathway and evaluate the potential of Akt-targeted therapy in a canine model of histiocytic sarcoma. We demonstrated Akt signaling to be active in 9 out of 10 canine HS tumor samples, regardless the presence of PTEN. Moreover, the Akt signaling

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Bruchez, Anna. "Niemann-Pick C1 Is Essential for Ebola Virus Infection and a Target of Small Molecule Inhibitors." Thesis, Harvard University, 2012. http://dissertations.umi.com/gsas.harvard:10654.

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Ebolavirus (EboV) is a highly pathogenic enveloped virus that causes outbreaks of zoonotic infection in Africa. The clinical symptoms are manifestations of the massive production of pro-inflammatory cytokines in response to infection and in many outbreaks, case fatality rate exceeds 75%. The unpredictable onset, ease of transmission, rapid progression of disease, high mortality and lack of effective vaccine or therapy have created a high level of public concern about EboV. Here we report the properties of a benzylpiperazine adamantane diamide-derived compound identified in a screen for inhibit

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CONTINO, GIANMARCO. "Rational design of targeted therapies for Pancreatic adenocarcinoma in K-ras GEMMs." Doctoral thesis, Università degli Studi di Milano-Bicocca, 2014. http://hdl.handle.net/10281/55465.

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L’adenocarcinoma pancreatico e’ una delle neoplasie con piu’ alta mortalita’ nei paesi occidentali, con una sopravvivenza media di 6 mesi e una percentuale estremamente bassa di sopravvivenza a lungo termine. L’evento principale nello sviluppo dell’adenocarcinoma pancreatico e’ la mutazione del gene KRAS, che tuttavia e’ particolarmente difficile da colpire a livello molecolare. Strategie terapeutiche piu’ efficaci per l’adenocarcinoma pancreatico possono derivare dall’impiego di terapie molecolari. L'obiettivo di questo lavoro e’ quello di identificare nuovi meccanismi e molecolari e strateg

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Lin, Ho-Pi. "Celecoxib its non-COX-2 targets and its anti-cancer effects /." Connect to resource, 2005. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1124114562.

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Thesis (Ph. D.)--Ohio State University, 2005.<br>Title from first page of PDF file. Document formatted into pages; contains xix, 94 p.; also includes graphics (some col.). Includes bibliographical references (p. 87-94). Available online via OhioLINK's ETD Center

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Sánchez, Guixé Mònica. "ER+ metastatic breast cancer targeted therapy: biomarkers of response and mechanisms of resistance to PI3K and FGFR inhibitors." Doctoral thesis, Universitat Autònoma de Barcelona, 2019. http://hdl.handle.net/10803/670148.

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La teràpia endocrina és un dels majors avenços en el tractament de càncer de mama (CM) dels últims 30 anys. Tot i això, les pacients acaben recaient degut a mecanismes de resistència, com ara les alteracions de la via de PI3K/mTOR i de FGFR. La via de PI3K està freqüentment alterada en CM, especialment en el conjunt luminal on el 30-40% de les pacients tenen mutacions al gen PIK3CA. S’han desenvolupat inhibidors específics d’mTOR i de PI3K (PI3Kinh), i alguns han sigut aprovats per la FDA per a CM ER+ metastàtic. Tanmateix, mecanismes de resistència han estat limitant la resposta. En aquest

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CANI, Alice. "Targeting the PI3K/Akt/mTOR signaling pathway as a new therapeutic strategy for personalized treatments in acute lymphoblastic leukemia." Doctoral thesis, Università degli studi di Ferrara, 2015. http://hdl.handle.net/11392/2388996.

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Acute lymphoblastic leukemia (ALL) is a hematologic malignancy characterized by the uncontrolled proliferation of lymphoblasts that accumulate in the blood, bone marrow and other organs. It represents 20% of adult acute leukemia and is the most common leukemia in children. The signal transduction pathway mediated by phosphatidylinositol 3-kinase (PI3K)/ Akt/mammalian target of rapamycin (mTOR) plays a key role in the regulation of important events for cells such as proliferation, differentiation and apoptosis, but also for the development of cancer and resistance to chemotherapy. In fact, the

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Guimaraes, Valdir. "Estudo da Estrutura dos Núcleos 17Ne e 13O pela reação de pick-up (3He, 6He)." Universidade de São Paulo, 1994. http://www.teses.usp.br/teses/disponiveis/43/43131/tde-05122013-110123/.

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The nuclear structme of 17Ne and 13O has been studied by the 20Ne(3He,6He)17Ne and 16O(3He,6He)13O reactions at 70 MeV and 80 MeV, respectively. Fifteen levels were identified, and angular distributions have been measured for nine of these levels in 17Ne, while for 13O eighteen levels were identified, but angular distributions were obtained for only ten levels. The observed transferred angular momentum dependence of these angular distributions allowed spin-parity assignments. The T= 3/2 quartet analog states in mass A=17 have been completed for six levels. The results of the isobaric multiple

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Hernández, Prat Anna 1984. "Antitumor effects of novel targeted therapies (TAK-228 and TAK-117) with high selectivity againts PI3K/AKT/mTOR pathway in bladder cancer : Defining molecular markers." Doctoral thesis, Universitat Pompeu Fabra, 2017. http://hdl.handle.net/10803/664507.

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El càncer de bufeta avançat s'associa amb un mal pronòstic i amb opcions limitades de tractament. Tot i l’èxit recent amb l'ús d'inhibidors immunitaris, no tots els pacients responen a la teràpia i encara hi ha la necessitat d'opcions alternatives. La ruta de PI3K/AKT/mTOR està sobreactivada sovint en aquesta patologia i pot ser un objectiu terapèutic potencial per a la intervenció terapèutica. Es va estudiar l'eficàcia antitumoral del TAK-228, un inhibidor oral de mTORC1 / 2 en models preclínics de càncer de bufeta amb alteracions en la transducció de senyals d'aquesta via. Es va demostrar un

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Herrera-Calderon, Oscar, Andres F. Yepes-Pérez, Jorge Quintero-Saumeth та ін. "Carvacrol: An in silico approach of a candidate drug on HER2, PI3Kα, mTOR, HER-α, PR, and EGFR receptors in the breast cancer". Hindawi Limited, 2020. http://hdl.handle.net/10757/655589.

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Carvacrol is a phenol monoterpene found in aromatic plants specially in Lamiaceae family, which has been evaluated in an experimental model of breast cancer. However, any proposed mechanism based on its antitumor effect has not been reported. In our previous study, carvacrol showed a protective effect on 7,12-dimethylbenz[α]anthracene- (DMBA-) induced breast cancer in female rats. The main objective in this research was to evaluate by using in silico study the carvacrol on HER2, PI3Kα, mTOR, hERα, PR, and EGFR receptors involved in breast cancer progression by docking analysis, molecular dynam

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Motloung, Setumo Victor. "Intense pulsed neutron generation based on the principle of Plasma Immersion Ion Implantation (PI3) technique." Thesis, University of the Western Cape, 2006. http://etd.uwc.ac.za/index.php?module=etd&action=viewtitle&id=gen8Srv25Nme4_9599_1182748458.

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<p>The development of a deuterium-deuterium/ tritium-deuterium (D-D/ D-T) pulsed neutron generator based on the principle of the Plasma Immersion Ion Implantation (PI3) technique is presented, in terms of investigating development of a compact system to generate an ultra short burst of mono-energetic neutrons (of order 1010 per second) during a short period of time (&lt<br>20&mu<br>s) at repetition rates up to 1 kHz. The system will facilitate neutron detection techniques, such as neutron back-scattering, neutron radiography and time-of-flight activation analysis.</p> <p><br /> Aspects address

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TALASILA, PHANI KUMAR. "NOVEL THYROID HORMONE TARGET GENES IN THE LIVER, AND THEIR ROLES IN THYROID HORMONE SIGNALING AND PHYSIOLOGY." Kent State University / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=kent1347474067.

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Coussy, Florence. "Identification de nouvelles thérapeutiques ciblées dans le cancer du sein à l’aide d’un large panel de tumeurs humaines xénogreffées." Thesis, Université Paris-Saclay (ComUE), 2019. http://www.theses.fr/2019SACLS560.

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Le cancer du sein triple négatif (CSTN) représente 10-15% des cancers du sein. Son pronostic est sombre en particulier face à la rareté des thérapies ciblées adaptées à ce sous type. Sa complexité de prise en charge est directement liée à sa grande hétérogénéité tant au niveau moléculaire que morphologique.Dans ce contexte, nous avons développés des modèles de Patient Derived Xenograft (PDX) issus de CSTN. Ce modèle, robuste, a la particularité de retenir les caractéristiques (histologiques, génotypiques mais aussi phénotypiques) des tumeurs observées chez les patients.Dans notre cohorte de 61

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Mordant, Pierre. "Cancer bronchique primitif, voies de signalisation intra-cellulaires et modèles précliniques." Phd thesis, Université Paris Sud - Paris XI, 2012. http://tel.archives-ouvertes.fr/tel-00809668.

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Contexte. Le cancer bronchopulmonaire (CBP) demeure la première cause de mortalité par cancer dans le monde. Malgré l'espoir suscité par le développement des thérapies ciblées, son pronostic demeure sombre, particulièrement dans les cas de CBP à petites cellules (CBP-PC) et de CBP non à petites cellules (CBP-NPC) présentant une activation de l'oncogène KRAS. Matériel et Méthodes. Nous avons mené 3 études successives, visant à (i) radiosensibiliser des modèles de CBP-PC par l'ajout d'un inhibiteur de BCL2, (ii) cibler des modèles de CBP-NPC mutés KRAS par l'association d'un inhibiteur de mTOR e

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Cerovac, Vesna [Verfasser]. "Studies on the PI3K-mTOR pathway as cytostatic treatment target in pituitary adenomas / vorgelegt von Vesna Cerovac." 2010. http://d-nb.info/1007160969/34.

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Lee, Chia Jung, та 李佳蓉. "HBV X protein upregulates RHAMM in hepatocellular carcinoma cells through negative regulation of PI3K/Akt/C/EBPβ pathway: Implication in cancer motogenicity and target therapy". Thesis, 2012. http://ndltd.ncl.edu.tw/handle/31363730321246499311.

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碩士<br>長庚大學<br>生物醫學研究所<br>100<br>Chronic hepatitis B virus (HBV) infection has been identified as a major risk factor in hepatocellular carcinoma (HCC), which is one of the most common cancers worldwide. Evidence suggests that the HBV X protein (HBx) plays a crucial role in HCC development. Genome-wide analysis identified earlier that the receptor for hyaluronan-mediated motility (RHAMM) represents a putative oncogene overexpressed in many human cancers, especially HCC. However, the role of RHAMM in establishment of tumorigenesis and chemoresistance in HCC is still unclear. This study presents

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ROHAN. "NEW INSIGHT: IN-SILICO ANALYSIS OF PHYTOCHEMICALS AS A THERAPEUTIC INTERVENTION AGAINST MENINGIOMA." Thesis, 2023. http://dspace.dtu.ac.in:8080/jspui/handle/repository/20118.

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Drug development for conventional delivery targets is the major challenge for therapeutic progress. PI3K signaling has shown a prominent role in progression of meningioma which subsequently makes these receptors a target for efficient treatment approach. Loss or alteration of NF2 (neurofibromin 2) with respect to its gene product merlin is crucially implicated in tumor development eventually leads to the meningioma. However, the interactions of meningioma pathophysiology (merlin) to many pathways makes it complicated. Different signalling pathways interacting with merlin are the

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木村, 薫., та Kaoru Kimura. "β-Hydroxy-β-methylbutyrate facilitates PI3K/Akt-dependent mammalian target of rapamycin and FoxO1/3a phosphorylations and alleviates tumor necrosis factor α/interferon γ-induced MuRF-1 expression in C2C12 cells". Thesis, 2014. http://hdl.handle.net/2237/20560.

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LAURA, CALABRESI. "Characterization of novel molecular targets and mechanisms in Philadelphia-negative Myeloproliferative Neoplasms." Doctoral thesis, 2018. http://hdl.handle.net/2158/1119126.

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During my PhD in Clinical and Experimental Oncology at the University of Florence, I focused on the molecular underpinnings in Philadelphia-negative Myeloproliferative neoplasms (MPNs). MPNs, including Essential Thrombocythemia (ET), Polycythemia Vera (PV) and Primary Myelofibrosis (PMF), are characterized by clonal proliferation of hematopoietic progenitor cells and dysregulated production of blood cells of different lineages. MPNs are characterized by occurrence of driver mutations in JAK2V617F, CALR and MPL. The exciting discovery of new genetic abnormalities in patients with MPNs, occurre

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BAZZICHETTO, CHIARA. "Tumor-stroma interactions influence the response to PI3K targeted agents in preclinical models of colorectal cancer (CRC)." Doctoral thesis, 2019. http://hdl.handle.net/11573/1244565.

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Introduction: One of the main obstacle to the successful development of therapeutic strategies remains the identification of biomarker underlying drug resistance. Recently, investigators have become more aware the role of the tumor microenvironment (TME) in cancer and the potential therapeutic opportunities that derive from suppressing potential resistance mechanisms arising microenvironmental interactions. The aim of this study was to set-up multicellular culture models to uncover the molecular mechanisms by which stromal/endothelial cells modulate response to signaling inhibitors and to iden

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Maiuri, Tamara Lise. "Specificity in PI3K-PKB/AKT-PTEN Signaling: Subcellular Locus-specific Functions of Pathway Targets." Thesis, 2010. http://hdl.handle.net/1807/26370.

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The PI3K-PKB/Akt-PTEN signal transduction pathway orchestrates a variety of fundamental cell processes and its deregulation is implicated in several human diseases, including cancer. While the importance of this pathway to many cellular functions is well established, the mechanisms leading to context-specific physiological outcomes in response to a variety of stimuli remain largely unknown. Spatial restriction of signaling events is one of the means to coordinate specific cellular responses. To investigate the subcellular locus-specific roles of the major PI3K effector PKB/Akt in various cell

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Qi-MingHuang and 黃啟銘. "Automatically Visual-Based Robot Arm Calibration and Pick and Place for Motion Target." Thesis, 2017. http://ndltd.ncl.edu.tw/handle/dur9fr.

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Frohlich, Bjorn Christian. "Development of automated iMALDI assays for the robust quantitation of cell signalling proteins in the PI3K pathway to improve guided cancer treatment." Thesis, 2021. http://hdl.handle.net/1828/13332.

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The PI3-kinase/AKT/mTOR pathway plays a central role in cancer signaling. While p110α is the catalytic α-subunit of PI3-kinase and a major drug target, PTEN is the main negative regulator of the PI3-kinase/AKT/mTOR pathway. PTEN and p110α protein expression in tumors is commonly analyzed by immunohistochemistry, which suffers from poor multiplexing capacity, poor standardization, and antibody cross-reactivity, and which provides only semi-quantitative data. Here, we present an automated, and standardized immuno-matrix-assisted laser desorption/ionization mass spectrometry (iMALDI) assay that

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Caleiras, Mariana Biscaia. "Targeted delivery of doxorubicin and C6-ceramide drug combinations to non-small cell lung cancer cells." Master's thesis, 2019. http://hdl.handle.net/10316/88212.

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Dissertação de Mestrado em Biotecnologia Farmacêutica apresentada à Faculdade de Farmácia<br>O cancro é, atualmente, a doença responsável pela segunda maior taxa de mortalidade a nível mundial. Entre todas as doenças oncológicas, o cancro do pulmão é o mais frequente e o mais fatal, por isso, representa uma necessidade médica relevante.Embora existam estratégias terapêuticas inovadoras para cancro do pulmão introduzidas recentemente, como os inibidores de tirosina cinase e os agentes anti-angiogénicos, a sua eficácia não é isenta de fenómenos de resistência. Para além disso, a quimioterapia co

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Gkountakos, Anastasios. "Assessing the potential role of Rictor expression as predictive factor of response to PI3K/mTOR pathway inhibitors in preclinical models of squamous cell lung cancer." Doctoral thesis, 2020. http://hdl.handle.net/11562/1017793.

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Squamous cell lung cancer (SQLC) is the second most prevalent histologic type of lung cancer and accounting for approximately 30% of newly diagnosed non-small cell lung cancer (NSCLC) cases. Systemic treatments for SQLC patients include cytotoxic chemotherapy and immune-oncology approaches. In contrast with lung adenocarcinoma, which is the other main subtype of NSCLC, no patient-tailored treatments are available so far for SQLC. Accumulating evidence suggests that the PI3K/mTOR axis is one of the most frequently altered pathways in SQLC. However, despite a plethora of clinical trials with num

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Avinash, Pradhan Shalmali. "Identification of Therapeutic Targets for Oral Squamous Cell Carcinoma." Thesis, 2013. http://etd.iisc.ac.in/handle/2005/3324.

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Oral squamous cell carcinoma (OSCC) is the most common head and neck cancer, with a worldwide incidence of 275,000 new cases annually (Warnakulasuriya, 2009). Globally, the head and neck carcinoma represents a major cause of morbidity and mortality and is the sixth most commonly occurring cancer (Warnakulasuriya, 2009). A majority (>90%) of the head and neck cancers are squamous in origin and thus are linguistically referred to as head and neck squamous cell carcinoma (HNSCC) (Warnakulasuriya, 2009). HNSCC includes cancers of the oral cavity, larynx and pharynx; oral cancer being the most comm

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Avinash, Pradhan Shalmali. "Identification of Therapeutic Targets for Oral Squamous Cell Carcinoma." Thesis, 2013. http://etd.iisc.ernet.in/2005/3324.

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Abstract:

Oral squamous cell carcinoma (OSCC) is the most common head and neck cancer, with a worldwide incidence of 275,000 new cases annually (Warnakulasuriya, 2009). Globally, the head and neck carcinoma represents a major cause of morbidity and mortality and is the sixth most commonly occurring cancer (Warnakulasuriya, 2009). A majority (>90%) of the head and neck cancers are squamous in origin and thus are linguistically referred to as head and neck squamous cell carcinoma (HNSCC) (Warnakulasuriya, 2009). HNSCC includes cancers of the oral cavity, larynx and pharynx; oral cancer being the most comm

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Lisboa, Rafael Jorge Fernandes. "Cancro oral e terapias alvo." Master's thesis, 2018. http://hdl.handle.net/10284/7411.

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O cancro oral é definido pela Classificação Internacional de Doenças pelo conjunto de tumores malignos que afetam qualquer localização da cavidade oral, dos lábios à garganta, incluindo as amígdalas e a faringe. É importante referir que o cancro oral é um dos tipos de doença oncológica mais comum a nível mundial e apresenta uma elevada taxa de mortalidade. De uma forma genérica, esta doença tem como principais abordagens terapêuticas a intervenção cirúrgica, a radioterapia e a quimioterapia, ou até mesmo a combinação destas terapias. Esta dissertação tem como base expor e compreender de

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