Tesis sobre el tema "He53"
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BON, GIULIA. "Dual targeting of HER3 and MEK may overcome HER3-dependent chemoresistance of colon cancers". Doctoral thesis, Università degli Studi di Roma "Tor Vergata", 2013. http://hdl.handle.net/2108/202145.
Texto completoAldana, Hidalgo Julio Xavier, Parodi Augusto José Amador, Palacios Jorge Martin Arredondo, Aguilar Carla Barrionuevo, Ortiz Carol Elizabeth Beltrán, Fuentes Carlos Arturo Capellino, Alcazar Martin Roberto Cervetto et al. "Estrategias de redacción - HE59 201801". Universidad Peruana de Ciencias Aplicadas (UPC), 2018. http://hdl.handle.net/10757/624389.
Texto completo(UPC), Universidad Peruana de Ciencias Aplicadas y Celis Ingunza Sandy Cecilia. "Creatividad Y Liderazgo-HE50-201601". Universidad Peruana de Ciencias Aplicadas (UPC), 2016. http://hdl.handle.net/10757/639326.
Texto completo(UPC), Universidad Peruana de Ciencias Aplicadas y Garcia Soria Juddy Grethel Nora. "Creatividad Y Liderazgo-HE50-201602". Universidad Peruana de Ciencias Aplicadas (UPC), 2016. http://hdl.handle.net/10757/639327.
Texto completo(UPC), Universidad Peruana de Ciencias Aplicadas y Ilizarbe Jurado Anndy Antonio. "Creatividad Y Liderazgo-HE50-201701". Universidad Peruana de Ciencias Aplicadas (UPC), 2017. http://hdl.handle.net/10757/639328.
Texto completoBass, Tarek. "Affibody molecules targeting HER3 for cancer therapy". Doctoral thesis, KTH, Proteinteknologi, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-204593.
Texto completoQC 20170330
Htun, van der Horst Edward. "The role of ErbB3/HER3 in gliomas and breast cancer". Diss., lmu, 2002. http://nbn-resolving.de/urn:nbn:de:bvb:19-5804.
Texto completoClaus, J. "The pseudokinase HER3 : structure/function relationships and inhibitor-induced signalling". Thesis, University College London (University of London), 2014. http://discovery.ucl.ac.uk/1457524/.
Texto completoFranks, P. W. "A He3 magnetometer for the EDM experiment". Thesis, University of Sussex, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.304321.
Texto completoXie, Ting. "Targeting `Undruggable' Cancer Proteins with Irreversible Small Molecule Inhibitors: Her3 and KRas". Thesis, Harvard University, 2014. http://dissertations.umi.com/gsas.harvard:11384.
Texto completoChemistry and Chemical Biology
Miller, Megan Jo. "Novel HER3 and IGF-1R Peptide Mimics and Synthetic Cancer Vaccines". The Ohio State University, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=osu1408981670.
Texto completoPark, Deric M., Jinkyu Jung, Jimmy Masjkur, Stylianos Makrogkikas, Doreen Ebermann, Sarama Saha, Roberta Rogliano et al. "Hes3 regulates cell number in cultures from glioblastoma multiforme with stem cell characteristics". Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2013. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-127014.
Texto completoHashimoto, Kenji. "Investigating a role of HER3 in anti-HER2 target therapy in breast cancer". Thesis, University of Oxford, 2014. http://ora.ox.ac.uk/objects/uuid:39025871-f32f-4e38-bd14-c13dbc9301f6.
Texto completoLazrek, Yassamine. "Ciblage tumoral du récepteur HER3 à l’aide d’anticorps : vers de nouvelles pistes thérapeutiques". Thesis, Montpellier 1, 2013. http://www.theses.fr/2013MON13524.
Texto completoDue to their implication in the cellular proliferation, the invasion and their surexpression in numerous cancers, the tyrosine kinase receptors of HER family constitute one of the best targets in oncology. Within this family, the human epidermal growth factor receptor 3 (HER3) plays a role in tumorigenesis of different cancers (Breast, melanoma, pancreas and ovary). This receptor is implicated in drug resistance and he is over expressed in cancers that are not eligible for the currently approved targeted therapies. To this end, we generated specific antibodies (Abs) against domain 1 (D1) and domain 3 (D3) of HER3 that recognize epitopes that do not overlap with the neuregulin-binding site. The fully human H4B-121 Ab and the mouse monoclonal Abs 16D3-C1 and 9F7-F11 inhibited tumor growth in nude mice xenografted with epidermoid, pancreatic, or triple-negative breast cancer cells independently of NRG addiction, HER2 status and p53/PTEN mutations. The combination of one anti-HER3 Ab and trastuzumab improved tumor growth inhibition in mice xenografted with HER2(low) cancer cell lines, for which trastuzumab alone shows no or moderate efficiency. Ab-induced disruption of tumor growth was associated with G1 cell cycle arrest, proliferation inhibition, and apoptosis of cancer cells. Anti-HER3 Abs blocked HER2/HER3 heterodimerization and HER3 phosphorylation at the cell membrane, leading to inhibition of phosphorylation of the downstream AKT targets murine double minute 2, X-linked inhibitor of apoptosis, and forkhead box O1. Anti-HER3 Abs can also induice antibody dependant cell-mediated cytotoxicity. This study demonstrates that anti-HER3 D1 and D3 Abs could represent a new option for immunotherapy of pancreatic and triple-negative breast cancers
Sollome, James Jerome. "Heregulin Activates a Novel HER2/HER3-MTK1-GIT1/ERK1/2 MAPK Signaling Pathway". Diss., The University of Arizona, 2014. http://hdl.handle.net/10150/315554.
Texto completoThomas, Gaëlle. "Ciblage de l'entité HER2/HER3 par des anticorps monoclonaux pour le traitement des cancers du pancréas exprimant faiblement HER2". Thesis, Montpellier 1, 2013. http://www.theses.fr/2013MON1T011.
Texto completoWith a 5-year survival lower than 5%, PDAC is one of the worst cancers in terms of mortality, and for which existing therapies are unsatisfying. This cancer is characterized by a dense fibrotic tissue and an over-developed stroma, in continual interaction with the tumor, promoting the development of an ideal environment for tumor progression.To date, gemcitabine is the only approved chemotherapy able to slightly increase patients' survival. The use of erlotinib, an EGFR targeting therapy, underlined that EGFR family targeting could be an interesting treatment strategy in this pathology, but that a better patients' selection is essential to increase therapeutic response. Two receptors of this family, HER2 and HER3, are able to dimerize to consititute an aggressive entity, involved in PDAC tumoral growth. Various recently developed techniques are used to quantify those dimers, in order to study their role, but also to target them and block their signaling in cancer cells. Pertuzumab is currently the only HER2-targeting monoclonal antibody able to block its dimerization and used in clinic. We first evaluated the role of HER3 as therapeutic target and prognostic marker of pertuzumab efficacy on HER2-low expressing PDACs. We then studied and compared therapeutic effects on pancreatic tumor proliferation of different antibodies targeting HER2 and/or HER3. Taken together, those results demonstrated that HER2/HER3 dimers targeting is a promising strategy to inhibit low-HER2 expressing pancreatic tumor growth, and that HER3 could be a pronostic marker for pertuzumab efficacy in those cancers
Rüder, Ulrike [Verfasser]. "HER3, CK5/6 und APOBEC3B als Biomarker in histologisch definierten Subtypen des Ovarialkarzinoms / Ulrike Rüder". Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2020. http://d-nb.info/1206185929/34.
Texto completoTeixidó, Febrero Cristina. "Study of the tumor sensitivity of the marine compound elisidepsin and her3 receptor in breast carcinomas". Doctoral thesis, Universitat Autònoma de Barcelona, 2012. http://hdl.handle.net/10803/96888.
Texto completoElisidepsin is a new synthetic depsipeptide, resultant from the PharmaMar Development Program to obtain synthetic products of marine origin-derived compounds. Elisidespin is a drug with antiproliferative activity against a wide range of tumors, including breast. The present research work focuses on the study and characterization of mechanisms of sensitivity and resistance to elisidepsin, and predictive factors of the drug response in an "in vitro" model of a broad panel of tumor cell lines. In this, we have seen that this compound has high cytotoxic activity in different cell lines, and although its mechanism of action is still unknown, we have seen evidence that relate the sensitivity of this chemical with signaling pathways dependent on HER receptors. After treatment we observed a decrease of the expression levels of the epidermal receptors, especially HER3 and with it a decreased activity of cell survival pathways by AKT. The working hypothesis is that HER3 receptor mediates signaling in response to elisidepsin. In order to assess this relationship, we saw that when HER3 expression is modulated in different cell lines their sensitivity to elisidepsin treatment is modified, making them more resistant when we down-regulated HER3 expression levels with a HER3-specific short hairpin and more sensitive when the receptor is overexpressed. All this points to an important role of HER3 receptor in mediating the response to this drug. Moreover, after the generation of a HER3 mutant tyrosine kinase free and cell viability and "cross-linking" assays a binding with HER3 receptor intracytoplasmic domain and elisidepsin was found. On the other hand, the study of HER3 receptor in human tumors is still not fully characterized, with a small number of publications. Since we saw a higher response of breast tumor cell lines expressing HER3, we decided to continue the project analyzing in more detail the levels of HER3 in a wide range of breast carcinoma samples from our database of Hospital Vall d'Hebron. The evaluation of HER3 in the clinical series led to interesting results, correlating the expression of HER3 with estrogen receptor levels, opening at the same time a new window for understanding the pathophysiological mechanisms of drug sensitivity and resistance to antiestrogen treatments. Finally, after confirming the association of the cellular response to elisidepsin with the expression of HER3, a possible association of HER3 levels with other important parameters in breast cancer carcinogenesis, such as hormone receptors, and the molecular study of the possible interrelationship of the biochemical pathways related to the expression of HER3 epidermal factor and estrogen receptors were also raised. For this, studies "in vitro" in a MCF-7 cellular model were made with an antiestrogen drug (fulvestrant), which showed an increase of HER3 expression levels after its administration and the involvement of this receptor in an increased resistance to fulvestrant treatment.
Göstring, Lovisa. "Cellular Studies of HER-family Specific Affibody Molecules". Doctoral thesis, Uppsala universitet, Enheten för biomedicinsk strålningsvetenskap, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-156730.
Texto completoDahlsson, Leitao Charles. "Rening av bi- och multispecifika cancer-terapeutiska affinitets-proteiner och c-terminalt modifierade anti-HER3 affibodies för avbildningsdiagnostik". Thesis, KTH, Skolan för bioteknologi (BIO), 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-190622.
Texto completoSchaller, Kerstin [Verfasser], Helga [Akademischer Betreuer] Bernhard y Christian [Akademischer Betreuer] Peschel. "Generierung zytotoxischer T-Zellen gegen das tumorassoziierte Antigen HER3 / Kerstin Schaller. Gutachter: Helga Bernhard ; Christian Peschel. Betreuer: Helga Bernhard". München : Universitätsbibliothek der TU München, 2012. http://d-nb.info/1031513787/34.
Texto completoNagel, Olaf. "HE5-CD52 und die [alpha]1-3-Fucosyltransferasen [Alpha-1-3-Fucosyltransferasen] des humanen Nebenhodens". [S.l.] : [s.n.], 2003. http://deposit.ddb.de/cgi-bin/dokserv?idn=968647464.
Texto completoMichaelsen, Vinicius Schenk. "Expressão da proteína erbB-3/HER3 em câncer de pulmão pela técnica de imuno-histoquímica e sua correlação com características clínicopatológicas". Pontifícia Universidade Católica do Rio Grande do Sul, 2008. http://hdl.handle.net/10923/4371.
Texto completoFour members belong to the erbB family, erbB1, erbB2, erbB3, and erbB4. Several reports have investigated the expression of members from this family, however with only few regarding to the role of erbB3 on non-small cell lung cancer (NSCLC). The aim of this study was to describe the expression frequency of erbB3 protein in NSCLC and evaluate a possible relationship with clinical parameters such as: age, gender, histological subtype, stage, histological grade, and survival. A total of 66 samples were analyzed by immunohistochemistry. ErbB3 expression frequency was detected in 57 samples (86. 4%). No statistical significance was found between expression degree and age, histological subtype, stage, histological grade, and survival. However, when samples were classified into two expression categories (0-75% and 75-100%) a statistic significance was found (P=0. 04) related to grade II (72. 5%). Although we did not found a relation between erbB3 expression and clinical and/or pathological parameters, probably due to the low sample number, it was possible to define that 86. 4% of samples did express the erbB3 protein in at least 25% of the tumor cells. This result agrees with other described in the literature. Investigation of other members belonging to this family in the same sample here evaluated could improve the results obtained since they have been implicated with tumor malignancy and that their role in tumorigenesis is probably associated to a collaborative interaction.
A família erbB é composta por quatro membros: erbB1, erbB2, erbB3 e erbB4. Essa família tem aparecido amplamente em diversos trabalhos, porém, o estudo particular da proteína erbB3 no câncer de pulmão ainda permanece muito restrito. O objetivo desse estudo foi descrever a freqüência de expressão da proteína erbB3 em amostras de câncer de pulmão não-pequenas (NSCLC) células, assim como correlacionar os achados da freqüência de expressão da proteína com as seguintes características clinico-patológicas dos pacientes como: idade, gênero, tipo histológico, estadiamento patológico, grau histológico, óbito e sobrevida. Um total de 66 espécimes foram analisados por imuno-histoquímica. A freqüência de expressão da proteína erbB3 esteve presente em 57 casos (86,4%). Não foi encontrada relação estatisticamente significativa entre a freqüência de expressão da proteína e as variáveis: idade, gênero, tipo histológico, estadiamento, grau histológico, óbito e sobrevida. Entretanto, quando as amostras foram agrupadas em categorias de expressão entre 0 e 75% e 75 e 100% das células tumorais positivas para a proteína erbB3, houve significância estatística com relação ao grau histológico (P=0,04) sendo o de maior freqüência o grau histológico tipo II (72,5%). Embora não tenha sido possível correlacionar a presença da expressão da proteína erbB3 com o prognóstico e os outros parâmetros clínicos, provavelmente devido ao pequeno número de amostras investigadas neste estudo, foi possível observar a presença desta proteína em 86,4% das amostras estudadas, comprovando que, assim como o EGFR e o erbB2, o erbB3 pode ser encontrado no NSCLC de forma bastante pronunciada. É possível que informações relativas à expressão dos outros membros desta família nestas mesmas amostras, possam trazer novas interpretações, lembrando, novamente, que seus membros, já caracterizados como proteínas participantes na oncogênese, atuam de forma sinérgica.
Sielaff, Bernhard. "Molekulare Analyse der Gene und Proteine der Cytochrom P450-haltigen Morpholin-Monooxygenase aus Mycobacterium sp. Stamm HE5". [S.l. : s.n.], 2005. http://deposit.ddb.de/cgi-bin/dokserv?idn=975691856.
Texto completoMalm, Magdalena, Nina Kronqvist, Hanna Lindberg, Lindvi Gudmundsdotter, Tarek Bass, Fredrik Y. Frejd, Ingmarie Hoiden-Guthenberg et al. "Inhibiting HER3-Mediated Tumor Cell Growth with Affibody Molecules Engineered to Low Picomolar Affinity by Position-Directed Error-Prone PCR-Like Diversification". Uppsala universitet, Enheten för biomedicinsk strålningsvetenskap, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-202922.
Texto completoRicalde, Rodrigues Alexandre. "Production d'He3 liquide polarisé par dilution et étude de la pression osmotique d'un mélange saturé He3-He4 polarisé". Université Joseph Fourier (Grenoble ; 1971-2015), 1995. http://www.theses.fr/1995GRE10240.
Texto completoEckrich, Caroline Elisabeth Verfasser] y Guido [Akademischer Betreuer] [Sauter. "Prävalenz der Tyrosinkinasen-Überexpression in humanen Zelllinien : Eine Gewebe-Mikroarray Analyse von BTK, ZAP70, HER3, HER4, JAK2 / Caroline Elisabeth Eckrich. Betreuer: Guido Sauter". Hamburg : Staats- und Universitätsbibliothek Hamburg, 2011. http://d-nb.info/1020457104/34.
Texto completoPeeß, Carmen Maria Verfasser] y Hans-Martin [Akademischer Betreuer] [Jäck. "Entwicklung von Antikörpern gegen den Domäne II beta-Hairpin des HER3-Rezeptors unter Verwendung der Thermus thermophilus SlyD-Scaffoldtechnologie / Carmen Maria Peeß. Gutachter: Hans-Martin Jäck". Erlangen : Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 2015. http://d-nb.info/1078774587/34.
Texto completoSrinivasan, Radhika. "Role of C-erB-4/HER4 and the alternatively spliced extracellular domain isoform of the c-erB-3/HER3 growth factor receptor in normal tissues and in cancer". Thesis, Imperial College London, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.391811.
Texto completoMichaelsen, Vinicius Schenk. "Express?o da prote?na erbB-3/HER3 em c?ncer de pulm?o pela t?cnica de imuno-histoqu?mica e sua correla??o com caracter?sticas cl?nicopatol?gicas". Pontif?cia Universidade Cat?lica do Rio Grande do Sul, 2008. http://tede2.pucrs.br/tede2/handle/tede/1485.
Texto completoA fam?lia erbB ? composta por quatro membros: erbB1, erbB2, erbB3 e erbB4. Essa fam?lia tem aparecido amplamente em diversos trabalhos, por?m, o estudo particular da prote?na erbB3 no c?ncer de pulm?o ainda permanece muito restrito. O objetivo desse estudo foi descrever a freq??ncia de express?o da prote?na erbB3 em amostras de c?ncer de pulm?o n?o-pequenas (NSCLC) c?lulas, assim como correlacionar os achados da freq??ncia de express?o da prote?na com as seguintes caracter?sticas clinico-patol?gicas dos pacientes como: idade, g?nero, tipo histol?gico, estadiamento patol?gico, grau histol?gico, ?bito e sobrevida. Um total de 66 esp?cimes foram analisados por imuno-histoqu?mica. A freq??ncia de express?o da prote?na erbB3 esteve presente em 57 casos (86,4%). N?o foi encontrada rela??o estatisticamente significativa entre a freq??ncia de express?o da prote?na e as vari?veis: idade, g?nero, tipo histol?gico, estadiamento, grau histol?gico, ?bito e sobrevida. Entretanto, quando as amostras foram agrupadas em categorias de express?o entre 0 e 75% e 75 e 100% das c?lulas tumorais positivas para a prote?na erbB3, houve signific?ncia estat?stica com rela??o ao grau histol?gico (P=0,04) sendo o de maior freq??ncia o grau histol?gico tipo II (72,5%). Embora n?o tenha sido poss?vel correlacionar a presen?a da express?o da prote?na erbB3 com o progn?stico e os outros par?metros cl?nicos, provavelmente devido ao pequeno n?mero de amostras investigadas neste estudo, foi poss?vel observar a presen?a desta prote?na em 86,4% das amostras estudadas, comprovando que, assim como o EGFR e o erbB2, o erbB3 pode ser encontrado no NSCLC de forma bastante pronunciada. ? poss?vel que informa??es relativas ? express?o dos outros membros desta fam?lia nestas mesmas amostras, possam trazer novas interpreta??es, lembrando, novamente, que seus membros, j? caracterizados como prote?nas participantes na oncog?nese, atuam de forma sin?rgica
Honkanen, T. (Tiia). "More efficient use of HER targeting agents in cancer therapy". Doctoral thesis, Oulun yliopisto, 2019. http://urn.fi/urn:isbn:9789526223445.
Texto completoTiivistelmä Syöpähoidot ovat kehittyneet huomattavasti, kun kohdennetut hoidot ja immunologiset hoidot ovat tulleet perinteisten hoitojen rinnalle. Usein näiden hoitojen hyötyä kuitenkin rajoittaa jo olemassa oleva lääkeresistenssi tai sen kehittyminen, mikä tulisi ottaa huomioon hoitoja suunniteltaessa. Tässä työssä tutkittiin immunologisia merkkiaineita, joilla voitaisiin ennustaa trastutsumabi-hoidon vastetta sekä potilaiden ennustetta levinneessä HER2-positiivisessa rintasyövässä. Tällä hetkellä trastutsumabi-hoitopäätös tehdään pelkän HER2-geenimonistuman mukaan ilman varmuutta siitä, hyötyykö potilas oikeasti hoidosta. Lisäksi tutkimme HER2- ja HER3-reseptorien merkitystä syövän kantasoluille ALK-translokoituneessa ei-pienisoluisessa keuhkosyövässä (NSCLC), sillä syövän kantasolut ovat yksi merkittävimmistä tekijöistä lääkeresistenssin kehittymisessä ja syövän uusiutumisessa. Työssä havaittiin, että kasvaimen keskellä oleva suuri määrä sytotoksisia T-soluja sekä M1-tyypin makrofageja on yhteydessä potilaiden parempaan ennusteeseen ja että kyseiset merkkiaineet ovat toisistaan riippumattomia. Merkkiaineet pystyivät ennustamaan myös taudin etenemistä sekä trastutsumabi-hoitokeskeytyksen pituutta. HER2- ja HER3-proteiinien tuotto lisäsi ALK-translokoituneiden NSCLC-solujen kantasolumaisia ominaisuuksia, jotka puolestaan vähenivät, kun proteiinien tuotto estettiin. Lisäksi HER2-HER3 -riippuvaiset syövän kantasolut säätelivät lääkeresistenssiä kyseisessä taudissa. Työn tulokset viittaavat siihen, että potilaita, joilla on suotuisa kasvaimen immunoprofiili (suuri määrä sytotoksisia T-soluja ja M1-tyypin makrofageja kasvaimen keskellä) pystyttäisiin hoitamaan keveimmillä hoidoilla ja HER2-hoitokeskeytys voisi olla mahdollinen näillä potilailla. Lisäksi työ korostaa HER2- ja HER3-reseptorien kohdentamista syövän kantasolumaisten solujen tehokkaamman tuhoamisen saavuttamiseksi
Huomautus/Notice Painetussa virheelliset ISBN -tunnukset: ISBN (print) 978-952-42-2343-8 pitäisi olla 978-952-62-2343-8. ISBN (PDF) 978-952-42-2344-5 pitäisi olla 978-952-62-2344-5. Printed version has incorrect ISBNs: ISBN (print) 978-952-42-2343-8 it should be 978-952-62-2343-8. ISBN (PDF) 978-952-42-2344-5 it should be 978-952-62-2344-5
Tulukcuoglu, Güneri Ezgi. "Development of microfluidic device for high content analysis of circulating tumor cells". Thesis, Paris 6, 2016. http://www.theses.fr/2016PA066583/document.
Texto completoMetastasis is the advanced stage of cancer progression and is the cause of 90% of deaths in cancer disease. During metastatic cascade, it is suggested that the successful metastatic initiation depends on the survival of circulating tumor cells (CTCs). CTCs are the cells that shed from the primary or secondary tumor sites into the blood circulation. it is now widely recognized as potential biomarker for companion diagnostics in which high number of CTCs in blood can indicate association with poor survival or high risk of disease progression. Besides, following the number of CTCs during the course of treatment can help to adapt the selected therapy and predict the treatment efficacy. On the other hand molecular characterization can provide patient stratification and identifying the therapeutic targets. However they are extremely rare in the bloodstream, estimated between 1-10 CTC among 6×106 leukocytes, 2×108 platelets and 4×109 erythrocytes per one mL of blood which makes their isolation very challenging. A very attractive way of isolation of CTCs is to integrate microfluidics. Microfluidics offers great advantages such as low volume of reagent consumption and short analysis times with automation as well as isolation and detection analysis can be integrated resulting in highly efficient biomedical devices for diagnostics. As parallel to state of the art, a powerful microfluidic device for circulating tumor cells capture and analysis had already been developed previously in our laboratory. The principle of capture is based on self-assembly of antibody-coated (EpCAM) magnetic beads in which the cells are enriched by EpCAM surface antigen which is found commonly in epithelial origin cancer cells. This system was already validated with cell lines and patients samples. However, the system did not allow isolation/detection of subpopulations of CTCs or performing high content molecular characterization. Therefore, my PhD project aimed at further improving the capabilities of the system on the main two aspects: targeting subpopulations of CTC and studying of protein interactions of CTCs in Ephesia System
Ta, Ngoc Ly. "Rôle des signaux pro-survie du récepteur Fas/CD95 dans le cancer colorectal : importance du dialogue moléculaire entre Fas et l’EGFR (Epidermal Growth Factor Receptor)". Thesis, Université Côte d'Azur (ComUE), 2018. http://www.theses.fr/2018AZUR4078.
Texto completoColorectal cancer (CRC) is the third most common malignant disease and the second most frequent cause of cancer-related death. The ErbB family of transmembrane receptor tyrosine kinases has been identified as a major driver of the development and progression of CRC and one its best-known member, the epidermal growth factor receptor (EGFR /ERBB1/Her1), considered one of the most important targets in CRC treatment. Two others members of the ErbB family, the receptors Her2 and Her3, also emerge as important new targets for CRC due to the somatic mutation, gene amplification or resistance to the anti-EGFR therapies. The transmembrane protein, Fas (TNFRSF6/CD95), is a member of the tumor necrosis factor receptor superfamily (TNFRSF). It can transmit multiple signals that lead to completely different cell fates. Depending on cellular contexts, Fas either initiates cell death by apoptosis, which is essential for shutting down chronic immune responses and preventing autoimmunity and cancer, or stimulates cell survival, proliferation, and motility, which can promote autoimmunity, cancer growth, and metastasis. With increasing evidence of Fas-mediated pro-survival signaling, the cancer-promoting activities of Fas are now recognized as significant and clinically relevant. While this signaling versatility has been particularly well demonstrated in colon cancer, the molecular mechanisms underlying the survivals pathways are still largely unknown. In this context, the main aim of my Ph.D. project was to study the importance of the crosstalks between Fas and the ErbB family members and more specifically to determine whether the Fas signaling could influence the cancer-promoting signaling of EGFR.More precisely, I describe how the Fas tyrosine phosphorylation status strongly influences the signaling of the EGFR pathway in colorectal cells. My data demonstrate that Fas in its prosurvival state, phosphorylated at Y291 (pY291-Fas), indeed interacts with EGFR and that this interaction significantly intensifies EGFR signaling in anti-EGFR-resistant colorectal cancer cells via the Yes-1/STAT3-mediated pathway. The pY291-Fas accumulates in the nucleus upon EGF treatment and promotes the nuclear localization of phospho-EGFR and phospho-STAT3, the expression of cyclin D1, the activation of STAT3-mediated Akt and MAPK pathways, and finally the cell proliferation and migration. Additionally, I also uncover the potential role that Her3, may play along with Fas, in the colorectal cancer cell escape from anti-EGFR inhibition. All together my Ph.D. studies provide a better understanding of the role of the Fas survival pathways in the ErBb signaling in CRC. Importantly, by demonstrating a connection between the emergence of resistance to anti-ErbB therapies and the Fas pro-survival signal, my work provides a rationale for the development of Fas/phospho-Fas targeted therapy as a new therapeutic option for overcoming anti-EGFR, in patients with secondary anti-EGFR resistance
Fridman, Belinda. "Process development for the production of a therapeutic Affibody® Molecule". Thesis, Uppsala universitet, Institutionen för biologisk grundutbildning, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-218861.
Texto completoTa, Ngoc Ly. "Rôle des signaux pro-survie du récepteur Fas/CD95 dans le cancer colorectal : importance du dialogue moléculaire entre Fas et l’EGFR (Epidermal Growth Factor Receptor)". Electronic Thesis or Diss., Université Côte d'Azur (ComUE), 2018. http://theses.univ-cotedazur.fr/2018AZUR4078.
Texto completoColorectal cancer (CRC) is the third most common malignant disease and the second most frequent cause of cancer-related death. The ErbB family of transmembrane receptor tyrosine kinases has been identified as a major driver of the development and progression of CRC and one its best-known member, the epidermal growth factor receptor (EGFR /ERBB1/Her1), considered one of the most important targets in CRC treatment. Two others members of the ErbB family, the receptors Her2 and Her3, also emerge as important new targets for CRC due to the somatic mutation, gene amplification or resistance to the anti-EGFR therapies. The transmembrane protein, Fas (TNFRSF6/CD95), is a member of the tumor necrosis factor receptor superfamily (TNFRSF). It can transmit multiple signals that lead to completely different cell fates. Depending on cellular contexts, Fas either initiates cell death by apoptosis, which is essential for shutting down chronic immune responses and preventing autoimmunity and cancer, or stimulates cell survival, proliferation, and motility, which can promote autoimmunity, cancer growth, and metastasis. With increasing evidence of Fas-mediated pro-survival signaling, the cancer-promoting activities of Fas are now recognized as significant and clinically relevant. While this signaling versatility has been particularly well demonstrated in colon cancer, the molecular mechanisms underlying the survivals pathways are still largely unknown. In this context, the main aim of my Ph.D. project was to study the importance of the crosstalks between Fas and the ErbB family members and more specifically to determine whether the Fas signaling could influence the cancer-promoting signaling of EGFR.More precisely, I describe how the Fas tyrosine phosphorylation status strongly influences the signaling of the EGFR pathway in colorectal cells. My data demonstrate that Fas in its prosurvival state, phosphorylated at Y291 (pY291-Fas), indeed interacts with EGFR and that this interaction significantly intensifies EGFR signaling in anti-EGFR-resistant colorectal cancer cells via the Yes-1/STAT3-mediated pathway. The pY291-Fas accumulates in the nucleus upon EGF treatment and promotes the nuclear localization of phospho-EGFR and phospho-STAT3, the expression of cyclin D1, the activation of STAT3-mediated Akt and MAPK pathways, and finally the cell proliferation and migration. Additionally, I also uncover the potential role that Her3, may play along with Fas, in the colorectal cancer cell escape from anti-EGFR inhibition. All together my Ph.D. studies provide a better understanding of the role of the Fas survival pathways in the ErBb signaling in CRC. Importantly, by demonstrating a connection between the emergence of resistance to anti-ErbB therapies and the Fas pro-survival signal, my work provides a rationale for the development of Fas/phospho-Fas targeted therapy as a new therapeutic option for overcoming anti-EGFR, in patients with secondary anti-EGFR resistance
Bezler, Martin [Verfasser]. "The HER3 receptor : role as an intervention target in ovarian cancer / Martin Bezler". 2010. http://d-nb.info/1007204923/34.
Texto completoNikolakopoulou, Polyxeni. "The role of endogenous neural stem cells (eNSCs) in metabolic syndrome and aging". Doctoral thesis, 2017. https://tud.qucosa.de/id/qucosa%3A33485.
Texto completoChandra, Ankush. "The role of ERBB3 inhibitors as cancers therapeutics". Thesis, 2015. https://hdl.handle.net/2144/16176.
Texto completoBellos, Angela Ogden. "Illuminating Actionable Biology in Breast Cancer: Novel Predictive and Prognostic Biomarkers". 2017. http://scholarworks.gsu.edu/biology_diss/185.
Texto completoHUANG, WEN-LIN y 黃雯琳. "Analysis of a promoter sequence that expressing hepatitis B virus RNA in a human hepatoma cell line, Hep3 B". Thesis, 1990. http://ndltd.ncl.edu.tw/handle/70114291330302077804.
Texto completoNagel, Olaf [Verfasser]. "HE5-CD52 und die α1-3-Fucosyltransferasen [Alpha-1-3-Fucosyltransferasen] des humanen Nebenhodens / vorgelegt von Olaf Nagel". 2003. http://d-nb.info/968647464/34.
Texto completoHtun, van der Horst Edward [Verfasser]. "The role of ErbB3-HER3 in gliomas and breast cancer : molecular mechanisms and potential role as therapeutic target / Edward Htun van der Horst". 2002. http://d-nb.info/965889564/34.
Texto completoSielaff, Bernhard [Verfasser]. "Molekulare Analyse der Gene und Proteine der Cytochrom P450-haltigen Morpholin-Monooxygenase aus Mycobacterium sp. Stamm HE5 / von Bernhard Sielaff". 2005. http://d-nb.info/975691856/34.
Texto completoΓρίβας, Πέτρος. "Διερεύνηση μοριακών προγνωστικών παραγόντων στον καρκίνο του παχέος εντέρου". Thesis, 2008. http://nemertes.lis.upatras.gr/jspui/handle/10889/2385.
Texto completoColorectal cancer is a major cause of cancer-related morbidity and mortality in the western world and has a significant impact on the health care systems. The deep understanding of molecular mechanisms that underline cellular transformation and tumor progression leads to the identification of key-molecules that are appropriate targets for sophisticated therapy in cancer. One such targeted approach exploits the presence of specific biomarkers that could be considered essential for tumor development. The role of such a biomarker, Human Εpidermal Receptor-1 (ΗΕR-1/EGFR), has been established in the development of colorectal cancer, suggesting the potential involvement of neighboring receptors, such as Human Εpidermal Receptor-3 (HER-3). HER-3 is a membranic receptor implicated in intracellular cell proliferation signaling. Thus, quantitative modifications in its expression and/or qualitative changes in its structure may contribute to cellular malignant transformation. The significance of HER3 expression, localization and phosphorylation remains elusive and data regarding its role in the pathogenesis, diagnosis, prognosis and management of colorectal cancer is limited. Apart from their mebranic counterparts, nuclear receptors are implicated in the regulation of gene transcription. Estrogen receptors (ER) α and β mediate the estrogen actions in the subcellular microenvironment. Differences in the incidence of colorectal cancer in the two genders have underlined the significance of ER expression in colorectal carcinogenesis. The specificity of estrogen activities in various cell types is mediated by the presence of tissue-specific coregulators (coactivators/corepressors). These proteins are specific transcription factors that bind to nuclear receptors, orchestrating their actions on the genome. Frequently, such coregulators are located in the cytoplasm, regulating the non genomic activity of the estrogens. Proline-, glutamic acid-, and leucine-rich protein 1 (PELP1), also known as modulator of non-genomic activity of ER (MNAR), amplified in breast cancer-1 (AIB1) and transcriptional intermediary factor-2 (TIF2) are considered major ER-coregulators. Thus, the investigation of their expression is inherent to the evaluation of estrogen-mediated mechanisms. The dynamic cross-talk between HER- and ER-driven signaling pathways has been described. The aim of this study is the investigation of the role of HER3, ER and coregulators PELP1/MNAR, AIB-1, TIF-2 (over)expression in the pathogenesis and prognosis of colorectal cancer. Material and Methods Sections from formalin-fixed, paraffin-embedded colorectal tissue blocks, derived from 140 patients with colorectal cancer, were used. HER-3 mRNA levels of expression were assessed by quantitative RT-PCR in 54 colorectal adenocarcinomas and 29 normal mucosa specimens. The expression levels of both phosphorylated and unphosphorylated HER-3 protein were assessed by immunohistochemistry in 110 normal mucosa specimens, 24 adenomas and 140 adenocarcinomas. The expression levels of ER α and β, PELP1/ΜΝΑR were assessed by immunohistochemistry in 88 normal mucosa specimens, 30 adenomas and 113 adenocarcinomas. Additionally, the expression levels of ΑΙΒ1 and TIF-2 protein were assessed by immunohistochemistry in 83 normal mucosa specimens, 30 adenomas and 110 adenocarcinomas. Results HER-3 was detected both in the cytoplasm and nucleus, whereas pHER-3 was observed in the nucleus and membrane of cells. A possible switch in HER-3 topography from the nucleus to the cytoplasm during colorectal tumorigenesis is suggested. The expression of pHER-3 did not differ significantly in normal tissue, adenomas and carcinomas, but was related to disease stage. HER-3 mRNA overexpression was significantly associated with decreased time to disease progression. It was also correlated with higher median age, left colon and rectal tumour sites and lymph node involvement. ERα expression was extremely rare in colorectal tissue of our cohort and its expression did not appear to be associated with colorectal carcinogenesis. ERβ and PELP1/MNAR were detected in the nucleus of epithelial, endothelial, inflammatory, smooth muscle cells and myofibroblasts. When intensity of staining was taken into account, the expression of both proteins was significantly increased in epithelial cells of carcinomas compared to normal mucosa. ERβ expression in epithelial cells was correlated with decreased disease progression-free survival. PELP1/MNAR overexpression in epithelial cells was found to be an independent favorable prognostic factor. AIB1 and TIF2 were detected in the nucleus of epithelial, endothelial, inflammatory, smooth muscle cells and myofibroblasts. The expression of both proteins was significantly increased in epithelial cells of carcinomas compared to normal mucosa. In carcinomas, a significant correlation between the levels of expression of AIB1 and TIF2 was noted, but there was no correlation between the expression patterns of these two proteins and ERβ. Although AIB1 overexpression was associated with local tumor invasion, it was also found to correlate independently with prolonged overall survival. TIF2 overxpression did not appear to correlate with clinicopathological parameters. Conclusion/Discussion This study highlights the significance of ΗΕR3 expression and phosphorylation in colorectal carcinogenesis, supporting also its potential prognostic significance. This study supports literature data regarding HER3 expression in colorectal tissue, while is the first to imply a possible prognostic significance of HER-3 mRNA expression levels and to suggest a topographic switch of HER3 protein during colorectal carcinogenesis. ERβ1 protein levels were found to increase during colorectal carcinogenesis, a finding which corresponds only to a small portion of literature data. The prognostic role of nuclear receptors depends on a number of factors, such as coregulator expression levels, chemical modifications, subcellular localization and ligand/hormone levels. The concomitant increase in the expression levels of coregulators PELP1/MNAR, ΑΙΒ1 and ΤΙF2 during colorectal carcinogenesis might imply their potential participation in estrogen-mediated signaling. However, the characteristic absence of strong correlation between their expression pattern and ERβ1 expression pattern underlines their pluripotent role and their possible contribution to estrogen-independent signaling. Further studies with a large number of patients, appropriately designed and conducted using sensitive experimental and statistical methods, are required for the confirmation of our hypothesis generation results. In the post-genomic era, identification of useful molecular biomarkers might contribute to the improvement of the management and prognosis of patients with colorectal cancer.