Ce travail de thèse est axé sur le développement d'une technique de traitement chimique par déchloration réductrice de l'hexachlorobutadiène (HCBD) et de l'hexachloroéthane (HCA). La première partie a consisté en l'acquisition de données expérimentales de solubilité des deux composés (i) à différentes températures et (ii) en présence de surfactants. Les essais en température ont notamment permis de proposer, par le calcul des variations des grandeurs thermodynamiques de dissolution, une explication physique à la présence d'un minimum de solubilité entre 12 et 45 °C. La seconde partie, basée sur une étude préalable de sélection d'un réactif pour son efficacité, a consisté principalement en l'étude du mécanisme de déchloration réductrice par les microparticules de Pd/Fe en suspension dans l'acide polylactique, un polymère biodégradable. Différentes conditions expérimentales ont permis de démontrer que l'hydrogène atomique est le principal réducteur du système. Plusieurs lois cinétiques ont ensuite été utilisées pour la modélisation de la disparition de HCBD et HCA en études individuelles et en mélange. / This work focused on the reductive dechlorination of hexachlorobutadiene (HCBD) and hexachloroethane (HCA). The first part consisted of experimental measurement of solubility data for both compounds (i) at different temperatures and (ii) in the presence of surfactants. Thermodynamic parameters for dissolution have been calculated in order to propose a physical explacation of the minimum solubility observed between 12 and 45 °C. The second part, based on a preliminary selection of a reaction for its efficiency, aimed to investigate the mechanism of the reductive dechlorination of HCBD and HCA by Pd/Fe microparticles in suspension in polylactic acid. Different experimental conditions have shown that atomic hydrogen is the main reductant of the system. Different kinetic laws were then used for the modeling of the disappearance of HCBD and HCA, taken separately and in mixture.

abstract: Osteosarcoma is the most common bone cancer in children and adolescents. Patients with metastatic osteosarcoma are typically refractory to treatment. Numerous lines of evidence suggest that cytotoxic T-lymphocytes (CTL) limit the development of metastatic osteosarcoma. I have investigated the role of Programmed Death Receptor-1 (PD-1) in limiting the efficacy of immune mediated control of metastatic osteosarcoma. I show that human metastatic, but not primary, osteosarcoma tumors express the ligand for PD-1 (PD-L1) and that tumor infiltrating CTL express PD-1, suggesting this pathway may limit CTL control of metastatic osteosarcoma in patients. PD-L1 is also expressed on the K7M2 osteosarcoma tumor cell line that establishes metastases in mice, and PD-1 is expressed on tumor infiltrating CTL during disease progression. Blockade of PD-1/PD-L1 interactions dramatically improves the function of osteosarcoma-reactive CTL in vitro and in vivo, and results in decreased tumor burden and increased survival in the K7M2 mouse model of metastatic osteosarcoma. My results suggest that blockade of PD-1/PD-L1 interactions in patients with metastatic osteosarcoma should be pursued as a therapeutic strategy. However, PD-1/PD-L1 blockade treated mice still succumb to disease due to selection of PD-L1 mAb resistant tumor cells via up-regulation of other co-inhibitory T cell receptors. Combinational α-CTLA-4 and α-PD-L1 blockade treated mice were able to completely eradicate metastatic osteosarcoma, and generate immunity to disease. These results suggest that blockade of PD-1/PD-L1 interactions in patients with metastatic osteosarcoma, although improves survival, may lead to tumor resistance, requiring combinational immunotherapies to combat and eradicate disease. / Dissertation/Thesis / Doctoral Dissertation Molecular and Cellular Biology 2015

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No. of bitstreams: 1 julianamelo.pdf: 1321154 bytes, checksum: 6613c9596412757aeb47ee110faa5b87 (MD5) Previous issue date: 2017-02-22 / A brucelose é uma doença infectocontagiosa causada por bactérias do gênero Brucella que acometem o homem e uma grande variedade de animais domésticos, resultando em prejuízos econômicos significativos aos sistemas de produção. Em humanos essa infecção pode causar febre ondulante, endocardite, artrite, osteomielite e complicações neurológicas enquanto em animais leva ao aborto e infertilidade. Sabe-se que a resposta imunológica a bactérias intracelulares como a Brucella ocorre essencialmente através da imunidade mediada por células, sendo macrófagos especialmente importantes no combate à infecção. Entretanto, apesar da efetividade da resposta, a B. abortus conta com diversos mecanismos de evasão, o que garante a sua sobrevivência no organismo hospedeiro. Dentre estes mecanismos, a modulação de células apresentadoras de antígenos tem sido apontada como um dos mais relevantes. Recentemente, diversos trabalhos têm evidenciado a importância das NTPDases e da molécula PD-1 na modulação da resposta imune. As NTPDases estão envolidas com a produção de adenosina que apresenta relevante caráter imunomodulador. Já a molécula PD-1 está associada a indução de um perfil anti-inflamatório com diminuição de IL-12 e aumento de IL-10. Neste contexto, o objetivo deste estudo foi determinar se a infecção com B. abortus é capaz de alterar a expressão destas moléculas e assim limitar a ação do sistema imune, favorecendo a sobrevivência do patógeno. Para isso, células RAW 264.7 foram infectadas com B.abortus e a modulação das moléculas CD80, CD86, CD40, MHCII, foi avaliada por citometria de fluxo. Em seguida, a expressão de CD39 também foi determinada por citometria de fluxo e por Western Blot. Por fim analisamos possíveis alterações na expressão da molécula PD-1 induzidas pela bactéria. Como resultados, foi confirmado que a infecção é capaz de inibir a expressão de CD80, CD86 e CD40, embora o mesmo não tenha sido observado com o MHCII. Além disso, a expressão de CD40 se mostrou diminuída mesmo após o estímulo com LPS. De forma surpreendente, foi observada uma diminuição na expressão das moléculas CD39 e PD-1, o que pode ser explicado pela menor ativação celular induzida pela infecção. Assim, os dados obtidos até o momento demonstram que as moléculas CD39 e PD-1 não são utilizadas pela Brucella para modular as APCs, mas são influenciados pela menor ativação celular induzida pelo patógeno. / Brucellosis is an infectious disease caused by bacteria of the genus Brucella that affect humans and a wide variety of domestic animals, resulting in significant economic losses to production systems. In humans the infection can cause undulant fever, endocarditis, arthritis, osteomyelitis and neurological complications while in animals leads to abortion and infertility. It is known that the immune response to intracellular bacteria such as Brucella occurs primarily by cell-mediated immunity, macrophage being especially important in fighting infection. However, despite the effectiveness of the response, B. abortus has several avoidance schemes, which ensures their survival in the host organism. Among these mechanisms, modulation of antigen-presenting cells has been identified as one of the most relevant. Recently, several studies have shown the importance NTPDase and PD-1 molecule to modulate the immune response. The NTPDase are envolidas with the production of adenosine which presents immunomodulatory relevant character. Since PD-1 molecule is associated with induction of an anti-inflammatory profile with decreased IL-12 and IL-10 increase. In this context, the aim of this study was to determine whether infection with B. abortus is able to alter the expression of these molecules and thus limit the action of the immune system, favoring the survival of the pathogen. To this end, RAW 264.7 cells were infected with B.abortus and modulation of CD80 molecules, CD86, CD40, MHCII, was evaluated by flow cytometry. Then the CD39 expression was also determined by flow cytometry and Western blot. Finally, we analyze possible changes in PD-1 molecule expression induced by bacteria. As a result, it was confirmed that the infection is capable of inhibiting expression of CD80, CD86 and CD40, although this has not been observed with MHCII. Additionally, CD40 expression showed decreased even after the stimulation with LPS. Surprisingly, it was observed a decrease in the expression of CD39 and PD-1 molecules, which can be explained by the lower cellular activation induced by the infection. Thus, the data obtained so far show that the PD-1 and CD39 molecules are not used by Brucella Modular APCs but are less influenced by cellular activation induced by the pathogen.

Neste trabalho foram produzidos eletrocatalisadores Pd/C, Au/C, PdAu/C, PdAuPt/C, PdAuBi/C e PdAuIr/C a partir do método de redução por borohidreto para oxidação eletroquímica de metanol, etanol e etilenoglicol. No método de redução por borohidreto, adiciona-se de uma só vez uma solução alcalina contendo borohidreto de sódio a uma mistura contendo água/2-propanol, precursores metálicos e o suporte de carbono Vulcan XC72. Os eletrocatalisadores obtidos foram caracterizados por espectroscopia de energia dispersiva de raios-X (EDX), difração de raios-X (DRX), microscopia eletrônica de transmissão (MET) e voltametria cíclica. A oxidação eletroquímica do metanol, etanol e etilenoglicol foi estudada por cronoamperometria utilizando a técnica do eletrodo de camada fina porosa. O estudo do mecanismo de oxidação eletroquímica do etanol foi estudado por meio da técnica de espectroscopia no infravermelho com transformada de Fourier (FTIR) in situ. Os melhores eletrocatalisadores foram testados em células alcalinas unitárias alimentadas diretamente por metanol, etanol e etilenoglicol. Estudos preliminares mostraram que a composição atômica adequada para preparar catalisadores ternários é igual a 50:45:05. De acordo com os experimentos eletroquímicos em meio básico, o eletrocatalisador PdAuPt/C (50:45:05) apresentou a maior atividade para oxidação eletroquímica de metanol, enquanto que, nas mesmas condições, o PdAuIr/C foi mais ativo para oxidação do etanol e o PdAuBi/C mais ativo para a oxidação do etilenoglicol. Estes resultados indicam que a adição de ouro na composição dos eletrocatalisadores contribui para uma maior atividade catalítica dos mesmos. Os resultados de FTIR mostraram que o mecanismo da oxidação do etanol se processa de modo indireto, ou seja, a ligação CC não é rompida, formando acetato. / In this study Pd/C, Au/C, PdAu/C, PdAuPt/C, PdAuBi/C and PdAuIr/C electrocatalysts were prepared by the sodium borohydride reduction method for the electrochemical oxidation of methanol, ethanol and ethylene glycol. This methodology consists in mix an alkaline solution of sodium borohydride to a mixture containing water/isopropyl alcohol, metallic precursors and the Vulcan XC 72 carbon support. The electrocatalysts were characterized by energy dispersive X-ray (EDX), X-ray diffraction (XRD), transmission electron microscopy (TEM) and cyclic voltammetry. The electrochemical oxidation of the alcohols was studied by chronoamperometry using a thin porous coating technique. The mechanism of ethanol electro-oxidation was studied by Fourier Transformed Infrared (FTIR) in situ. The most effective electrocatalysts were tested in alkaline single cells directly fed with methanol, ethanol or etylene glycol. Preliminary studies showed that the most suitable atomic composition for preparing the ternary catalysts is 50:45:05. Electrochemical data in alkaline medium show that the electrocatalyst PdAuPt/C (50:45:05) showed the better activity for methanol electrooxidation, while PdAuIr/C was the most active for ethanol oxidation and PdAuBi/C (50:45:05) was the most effective for ethylene glycol oxidation in alkaline medium. These results show that the addition of gold in the composition of electrocatalysts increases their catalytic activities. The spectroelectrochemical FTIR in situ data permitted to conclude that C-C bond is not broken and the acetate is formed.

Modulação da resposta imune no local do tumor é um mecanismo crítico envolvido com evasão dos tumores. Sinais de PD-1 e PD-L1/PD-L2 podem estar envolvidos com o escape tumoral. Entretanto, pouco se sabe a respeito destas moléculas no desenvolvimento de carcinoma de células escamosas. No presente estudo, nós investigamos a expressão de PD-1 sobre células T das lesões e linfonodos de carcinomas de células escamosas. A carcinogênese de pele foi induzida quimicamente com DMBA/PMA em camundongos. A caracterização da expressão de PD-1, PD-L1 e PD-L2 na lesão e linfonodos foram analisados por citometria de fluxo. A produção IL-10, IL-12, TGF- e IFN- foi determinada por ELISA. Camundongos tratados com DMBA/PMA apresentaram maior taxa de papilomas e progressão para carcinoma de células escamosas. Nós encontramos também que células T CD4+PD-1+ migraram para o local do tumor e que maior nível de CD4+PD-1+, CD8+PD-1+, CD14+PD-1+ e CD4+PD-L1+ foram detectados nos linfonodos quando comparados com o grupo controle. Além disso, as produções de IL-12, IFN- e TGF-, mas não IL-10, foram altamente detectadas nas lesões comparada com do grupo controle. Estes dados indicam que a expressão de PD-1 está regulada positivamente sobre linfócitos infiltrados nos tumores e linfonodos. Este fato e os altos níveis de TGF- e IL-10 podem contribuir para supressão da resposta imune antitumor. / Modulation of immune response in tumor site is a critical mechanism involved with tumor evasion. PD-1 and PD-L1/PD-L2 signals could be involved in tumor escape. However, little is known about the role of these molecules in squamous cell carcinoma development. In the present study, we investigated the expression of PD-1 on T cells from squamous cell carcinoma lesions and lymph nodes. Skin carcinogenesis was chemically induced with DMBA/PMA in mice. Characterization of PD-1, PD-L1 and PD-L2 expression in the lesion and lymph nodes were analysed by flow cytometry. IL-10, IL-12, TGF- and IFN- production was determined by ELISA. DMBA/PMA-treated mice showed higher rate of papillomas and progression to squamous cell carcinoma. We also found that CD4+PD-1+ T cells migrated to the tumor site and that higher level of CD4+PD-1+, CD8+PD-1+, CD14+PD-1+ and CD4+PD-L1+ were detected in the lymph nodes when compared with the control group. Besides, IL-12, IFN- and TGF-, but not IL-10, productions were higher detected in the lesions compared with the control group. These data indicate that PD-1 expression is up-regulated on tumor infiltrating lymphocytes and lymph nodes. This fact and high levels of TGF- and IL-10 may contribute to suppression of anti-tumor immune response.

Introduction: Human papillomavirus (HPV) is changing the prevalence, survival and treatment paradigms in oropharyngeal squamous cell carcinoma (OPSCC). Improved survival of patients with HPV positive compared to HPV negative OPSCC has led to trials of treatment de-escalation. Current HPV detection methods are imprecise, therefore standardised assessment of transcriptionally active HPV in OPSCC is required. Furthermore, the differences in immune characteristics and/or the hypoxia response/effects could explain observed differences in prognosis between HPV positive and negative OPSCC. Rigorous HPV detection and subsequent biomarker evaluation should provide additional information required before introduction of treatment de-escalation in broad patient groupings. Methods: The study cohort was 218 patients with OPSCC who received radiotherapy with curative intent. HPV status was determined on pre-treatment, formalin-fixed paraffin-embedded blocks using: 1) polymerase chain reaction (PCR); 2) in-situ hybridisation (ISH) and 3) immuno-histochemistry (IHC). QuantiGene multiplex assay was designed to detect mRNA of reference sequences of the common high-risk HPV types (16, 18, 33, 35, 45, 52 and 58). HPV detection methods were compared with mRNA quantification. Multimarker IHC of immune cell markers using chromogenic and fluorescent staining was performed, analysed and compared with single marker IHC using automated multispectral image analysis. A validated multiplex IHC method was used for a) chromogenic (CD3, CD4, CD8, and FoxP3) and b) fluorescent (CD8, CD68 and PD1/PD-L1) evaluation in tumour and stroma compartments. Single marker IHC was used to investigate tumour hypoxia markers (HIF-1α and CA-IX) in HPV positive and negative OPSCC. Results: p16 IHC and ISH were the most sensitive and specific, respectively, for classifying HPV status. The combination of the three tests had the highest positive/negative predictive values compared with QuantiGene mRNA detection. Multiplex validation showed that, for serial sections up to 6 μm apart, there were highly significant correlations (P<0.0001) between single and multiplex counts for both chromogenic and fluorescent IHC. Overall there was less variation in cell counts with fluorescent staining when compared to chromogenic staining. Multiplex IHC of TILs in HPV positive and negative OPSCC showed higher infiltration in both tumour and stromal areas of CD3+CD4+ and CD3+CD8+ T cells but not CD4+FoxP3 Tregs in HPV positive compared with HPV negative OPSCC. Only CD3+CD8+ stromal and not tumour area infiltration was associated with increased survival (P=0.02). PD-L1 expression was higher in HPV negative OPSCC and this was related to macrophage (CD68) expression of PD-L1. In HPV negative tumours infiltration with CD68+PD-L1 was associated with a good prognosis. HPV negative patients had higher expression of HIF-1α but not CA-IX. High expression of both markers was associated with a poor prognosis irrespective of HPV status. Conclusions: There are other prognostic factors operating in the larger subdivision of HPV positive and negative OPSCC. Precise HPV detection and inclusion of other prognostic factors is required before treatment de-escalation is used. Expression of immune inhibitory factors (PD1/PD-L1) alone without contextualisation with immune cell density is insufficient for patient prognostication and potential selection for therapy using immune checkpoint inhibitors. Hypoxia modification of radiotherapy should be explored in both HPV positive and negative OPSCC.

No description available.

Résumé : L’immunothérapie anti-PD1 est à l’origine de résultats cliniques impressionnants dans le traitement de certains cancers comme le mélanome métastatique ou le lymphome Hodgkinien. Néanmoins, les rechutes sont fréquentes et certaines tumeurs y sont d’emblée résistantes. Par ailleurs, l’étude du complexe d’initiation de la traduction eIF4F gagne de plus en plus d’intérêt dans le domaine du cancer. En effet, eIF4F joue un rôle fondamental dans la biologie des cancers grâce au contrôle sélectif de la synthèse de protéines impliquées dans le développement tumoral.Dans cette étude, nous montrons que l’inhibition du complexe eIF4F, en plus d’avoir un effet antitumoral directe via l’inhibition de la croissance tumorale in-vitro, a une action indirecte grâce à l’inhibition de l’expression de PD-L1 sous IFN-g, évitant ainsi le blocage des lymphocytes cytotoxiques suite à l’engagement PD-1/PD-L1. Dans un modèle murin de mélanome, nous avons montré une inhibition de la croissance tumorale grâce à l’inhibition de l’expression de PD-L1, uniquement dans des souris immunocompétentes, montrant ainsi le rôle fondamental du système immunitaire. Nous avons ensuite identifié la voie de régulation de PD-L1 par eIF4F via une régulation traductionnelle de l’ARNm de STAT1, principal facteur de transcription de PD-L1 sous IFN-g.Cette étude apporte une nouvelle preuve de l’intérêt des inhibiteurs d’eIF4F dans le cancer en démontrant leur effet immunothérapeutique via l’inhibition de PD-L1, évitant ainsi l’interaction PD-1/PD-L1 qui conduit à l’échappement des tumeurs. Ces résultats ouvrent la voie vers de nouvelles stratégies dans la lutte contre le cancer. / The eukaryotic translation initiation complex eIF4F is subject of an increased interest in the field of cancer. This heterotrimeric complex, comprising the RNA helicase eIF4A, the cap-binding protein eIF4E and the scaffold protein eIF4G, is known to be more abundant and active in tumor cells than non-malignant counterparts.In a previous work, we showed that this complex is implicated in the resistance to melanoma-targeted therapies (Boussemart et al, Nature 2014). Furthermore, it is implicated in the resistance to various chemotherapies. Thus, agents targeting the eIF4F complex appear as promising tools in the field of cancer therapy.On the other hand, immunotherapy, by (re)stimulating and enhancing the host immune system against tumors is giving good clinical results in oncology treatment and appears nowadays as the most promising approach to fight cancer, especially anti-PD1 treatment. Even though immunotherapy has demonstrated remarkable results in curing some established cancers, such as advanced melanoma or Hodgkin’s lymphoma, many tumors relapse or fail to respond. It is thus important to still look for a new strategy enhancing the efficacy of actual treatments. Here, we propose to study the impact of inhibiting the eIF4F complex on the tumor-specific immune response.

Les Myeloid-Derived Suppressor Cells (MDSC) sont une population hétérogène de cellules myéloïdes immatures, regroupées en deux sous-populations : les monocytiques-MDSC (M-MDSC) et les polymorphonucléaires-MDSC (PMN-MDSC). Ces cellules ont des capacités immunosuppressives et peuvent exprimer le ligand PD-L1 induisant l’anergie des lymphocytes T qui expriment le marqueur PD-1. Au cours du sepsis, divers bouleversements immunologiques surviennent, et la fonction majeure des MDSC est probablement de réguler l’hyper-inflammation en participant à l’état d’immunodépression rencontré chez les patients. Ceux-ci ont alors un risque de développer des infections secondaires, et de réactiver des virus jusque-là en latence. Notre étude a pour objectifs de mettre en évidence l’origine des MDSC dans le sepsis, et d’approfondir leurs rôles dans l’état d’immunosuppression, notamment dans la réactivation du Torque Teno Virus (TTV). Nos résultats montrent tant ex vivo qu’in vitro, que dans le sepsis, les MDSC sont produites par la moelle osseuse, sous l’influence du G-CSF et de l’IL-6. Ces cellules exprimant PD-L1, sont augmentées dans le sang très tôt dans le sepsis et persistes au cours de l’hospitalisation. L’augmentation de la charge virale du TTV est observée dans le sang périphérique des patients, mais n’est pas corrélée à la fréquence des MDSC. Ces résultats suggèrent que lors d’un sepsis, l’orage cytokinique stimule la production de MDSC exprimant PD-L1 par la moelle osseuse, qui une fois en périphérie, vont participer à l’immunosuppression générale. / Myeloid-Derived Suppressor Cells (MDSC) are a heterogeneous population of immature myeloid cell, and are regrouped in two subsets: the monocytic-MDSC (M-MDSC) and the polymorphonuclear-MDSC (PMN-MDSC). These cells have immunosuppressive capacities and mainly act on T cells. MDSC can express the ligand PD-L1 and induce PD-1 expressing-T cells exhaustion. During sepsis, several immunological changes occur, and MDSC probably downregulate the hyper-inflammatory state, contributing to the immunosuppression phase encountered in patients after a sepsis. Immunocompromised patients can develop secondary infections, and reactivate latent virus. The aims of our study were to highlight the origin of MDSC in sepsis, and to explore their roles in the immunosuppression state, especially in the Torque Teno Virus (TTV) reactivation. Our results show, both ex vivo and in vitro, that in sepsis, MDSC originate from bone marrow are induced by G-CSF and IL-6. These PD-L1 expressing-cells are increased in peripheral blood very early in sepsis, and persist during hospitalization. These MDSC are able to inhibit T cells in vitro. The increase of TTV viral load is observed in peripheral blood of patients but is not correlated with MDSC frequencies. These results suggest that during sepsis, the cytokine storm boosts PD-L1 expressing MDSC’s production by bone marrow, which contribute in peripheral blood to the immunosuppression

Dans le domaine de la cristallisation des fibres monocristallines par la technique de la micro-pulling down (µ-PD), les résultats récents sur les performances des fibres monocristallines (optique, laser, scintillateur) ont montré l’étendue des champs d’applications ouverts aux fibres cristallines. La course à la croissance cristalline, la fabrication de fibres cristallines performantes et la maitrise des procédés sont des enjeux de recherche dans un nombre important de laboratoires à travers le monde. Les fibres monocristallines de saphir et du YAG dopées Cérium (Ce3+) sont des formats à forte valeur ajoutée. Elles sont susceptibles d’être utilisées dans un large domaine d’applications, d’où la nécessité de contrôler et de maitriser la technologie de fabrication. En fonction des conditions de tirage (gradient de température, orientations cristallographiques des germes, vitesses de tirage), nous nous sommes intéressés à l’étude des bulles et des contraintes résiduelles dans le saphir tiré par µ-PD. La ségrégation du Cérium et la propagation de la lumière ainsi que l’atténuation dans les fibres YAG-dopées Cérium (Ce3+) ont été étudiées en fonction des vitesses de tirage. Nous avons étudié tous ces phénomènes ainsi que les mécanismes mis en jeu. La variation de la vitesse de tirage est en corrélation avec la distribution des bulles, la ségrégation du Ce et l’atténuation. A travers ce travail, on est en mesure de dire que les phénomènes à l’origine de la présence, de la répartition des bulles dans les fibres saphir et la ségrégation du Cérium dans le YAG ont été significativement éclaircis et que, à partir de ces résultats, des améliorations peuvent être apportées aux procédés technologiques de tirage par µ-PD / In the field of crystallization of single crystal fibers by micro-pulling down (µ-PD) technique, the recent results on the performance of single crystal fibers (optical, laser, scintillator) have shown the wide range of applications open to crystalline fibers. The race for crystal growth, the manufacture of high-performance crystal fibres and process control are research challenges in a large number of laboratories around the world. Cerium-doped monocrystalline sapphire and YAG fibres (Ce3+) are high value-added formats. They are likely to be used in a wide range of applications, hence the need to control and master manufacturing technology. Depending on the growth conditions (temperature gradient, crystallographic orientations of the germs, growth speeds), we were interested in studying the bubbles and residual stresses in the sapphire pulled by µ-PD. The segregation of Cerium and the propagation of light as well as the attenuation in YAG-doped Cerium fibres (Ce3+) were studied as a function of growth speeds. We have studied all these phenomena and the mechanisms involved. The variation in the growth rate is correlated with the distribution of bubbles, the segregation of Ce and the attenuation. Through this work, it can be said that the phenomena at the origin of the presence, distribution of bubbles in sapphire fibres and the segregation of Cerium in the YAG have been significantly clarified and that, from these results, improvements can be made to the technological processes of pulling by µ-PD