40 results on '"Bikfalvi, A"'
Search Results
2. [Science, truth and beliefs]
- Author
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Andreas, Bikfalvi
- Subjects
Evidence-Based Medicine ,Knowledge ,Science ,Culture ,Human Characteristics ,Humans ,Mythology ,Social Environment ,Dissent and Disputes ,Ethical Relativism - Abstract
This article aims at discussing some aspects of the relationship between science, truth and belief. I will primarily focus on the scientific activity in the biological and medical sciences and how it relates to the notion of truth and belief and not discuss the relationship with specific religions. Science has specific methodologies to obtain knowledge. Philosophers have analyzed how scientific knowledge is acquired and have tried to identify its characteristics and to establish some general rules of how knowledge through science is gained. Radical theorists have disputed the value of the scientific method despite science's indisputable successes. If science is a rational activity, it is not free from belief. Belief can have a positive and negative impact on the acquisition of scientific knowledge and the idea of human nature. These different issues will be discussed in depth in this article.
- Published
- 2018
3. Science, vérité et croyances.
- Author
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Bikfalvi, Andreas
- Published
- 2018
- Full Text
- View/download PDF
4. [Tumoral angiogenesis: models, targets and inhibition]
- Author
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Andreas, Bikfalvi
- Subjects
Neovascularization, Pathologic ,Neoplasms ,Unfolded Protein Response ,Animals ,Gene Expression Regulation, Developmental ,Humans ,Neovascularization, Physiologic ,Angiogenesis Inhibitors ,Chick Embryo ,Endoplasmic Reticulum ,Hypoxia-Inducible Factor 1, alpha Subunit ,Cell Hypoxia ,Chorioallantoic Membrane - Abstract
Angiogenesis is a basic process during development and in pathology as well. The molecular networks involved in angiogenesis are not totally understood. We have recently developed a new model for tumoral angiogenesis in the chicken embryo, which allows large scale studies. On the other hand we have uncovered a new induction pathway, which involves stress of the endoplasmic reticulum. These investigations open up novel prospects for the future.
- Published
- 2009
5. [Tumor angiogenesis]
- Author
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Andréas, Bikfalvi
- Subjects
Fibroblast Growth Factors ,Vascular Endothelial Growth Factor A ,Neovascularization, Pathologic ,Vascular Endothelial Growth Factors ,Neoplasms ,Humans ,Angiogenesis Inhibitors ,Lymphangiogenesis ,Growth Substances ,Angiopoietins ,Signal Transduction - Abstract
Following the work of Folkman, it appears that angiogenesis, which consists in the formation of new blood vessels able to deliver oxygen and nutriments to tumor cells, is a major step in the evolution of tumors, which can only grow after the onset of the angiogenic switch. Numerous factors play a role in angiogenesis stimulation or inhibition : the vascular endothelial growth factor and fibroblastic growth factors as well as angiopoietin are proangiogenic, whereas angiostatin and platelet factor 4 are anti-angiogenic. The discovery of these molecules and of the molecular mechanisms of their activity allowed the identification of new therapeutic targets, which appear relevant for the treatment of cancer.
- Published
- 2007
6. [Experimental approaches to study in vivo angiogenesis]
- Author
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Witold, Kilarski and Andreas, Bikfalvi
- Subjects
Neovascularization, Pathologic ,Neovascularization, Physiologic ,Chick Embryo ,Chorioallantoic Membrane ,Drug Combinations ,Neoplasms ,Models, Animal ,Animals ,Blood Vessels ,Corneal Neovascularization ,Proteoglycans ,Collagen ,Laminin ,Rabbits ,Ear, External - Abstract
Angiogenesis has become a major issue in oncology. Different in vivo angiogenesis assays have been developed in order to better understand fundamental aspects of vascular development or to investigate the effect of therapeutic molecules on blood vessel growth. In this article, we will briefly review the main in vivo angiogenesis assays relevant to oncology and discuss their advantages and disadvantages.
- Published
- 2007
7. [Understanding in treating gliomas: an adequate experimental model for each question]
- Author
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Sophie, Javerzat, Andréas, Bikfalvi, and Martin, Hagedorn
- Subjects
Disease Models, Animal ,Mice ,Brain Neoplasms ,Animals ,Humans ,Chick Embryo ,Glioma ,Microarray Analysis ,Chorioallantoic Membrane ,Neoplasm Transplantation ,Rats - Abstract
Malignant glioma are especially difficult to model in vivo. Here we review the most recent strategies for designing relevant models of glioma. These should greatly contribute to identification of new tumor regulating molecules and facilitate testing of inhibitors to be used in therapeutical trials as well as the drug resistance that they might confer.
- Published
- 2005
8. [Role of fibroblast growth factor-2 in tumor angiogenesis]
- Author
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A, Bikfalvi
- Subjects
Neovascularization, Pathologic ,Animals ,Humans ,Fibroblast Growth Factor 2 - Abstract
Angiogenesis reflects a balance between stimulating and inhibitory factors, among which fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor (VEGF) play a central role. FGF-2 stimulates endothelial cell growth and migration and enhances angiogenesis, both in vitro and in vivo. FGF-2 binds to a specific receptor (FGF R1) at the surface of endothelial cells. In addition to its extracellular effects, FGF-2 exerts intracellular effects that seem to be independent from tyrosine kinase-type receptors. FGF-2 is produced by several tumor types, including brain tumors, skin tumors, and fibrosarcomas. FGF-2 may play a pivotal role in angiogenesis in these tumors.
- Published
- 1999
9. [Angiogenesis and neoangiogenesis]
- Author
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C, Savona, S, Javerzat, C, Perollet, and A, Bikfalvi
- Subjects
Neovascularization, Pathologic ,Humans ,Neovascularization, Physiologic ,Angiogenesis Inducing Agents ,Endothelium, Vascular ,Urokinase-Type Plasminogen Activator - Abstract
Angiogenesis, the development of new capillary networks from the normal vasculature, is a fundamental process during embryogenesis. In adulthood, angiogenesis contributes to corpus luteum formation, placental implantation and wound healing and is also required in some pathological conditions such as several intraocular syndromes, growth of solid tumors, and metastasis. Many factors are involved in the regulation of neovascularisation among which FGF-2 (fibroblast growth factor-2) and VEGF (vascular endothelial growth factor) are considered as key inducers. Their biological activity is highly controlled by extracellular matrix components and angiostatic factors. Better understanding of the molecular mechanisms regulating angiogenesis should contribute to the development of new molecules to be used for the treatment of neovascularisation-linked diseases.
- Published
- 1998
10. [Angiogenesis and cancer]
- Author
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A, Bikfalvi, S, Javerzat, C, Perollet, and C, Savona
- Subjects
Neovascularization, Pathologic ,Neoplasms ,Humans ,Neoplasm Invasiveness ,Neoplasm Metastasis ,Growth Substances - Abstract
Tumor invasion and dissemination is tightly controlled by angiogenesis. In recent years, a number of angiogenic factors and inhibitors have been identified. However, the molecular mechanisms leading to this phenomenon are still incompletely understood. In this review, we focus on recent developments in the angiogenesis field. We will summarize our present knowledge about the molecular mechanisms involved in angiogenesis and about the factors that control this phenomenon. We will then shortly discuss the pharmacological modulation and the therapeutic and clinical implications for cancer biology.
- Published
- 1998
11. Expression et valeur pronostique de cxcl4, cxcl4l1, et cxcr3b dans le carcinome à cellules rénales claires (CCRc)
- Author
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Donon, L., Bernhard, J.-C., Soulet, F., Drutel, G., Leste-lasserre, T., Yacoub, M., Le Bail, B., Ballanger, P., Ferrière, J.-M., and Bikfalvi, A.
- Published
- 2012
- Full Text
- View/download PDF
12. Angiogenèse tumorale : modèles, cibles et inhibition.
- Author
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Bikfalvi, Andreas
- Published
- 2009
- Full Text
- View/download PDF
13. [Remarks on surgery of bronchial cancer]
- Author
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A, Bikfalvi
- Subjects
Radiography ,Mediastinoscopy ,Bronchial Neoplasms ,Humans ,Neoplasm Metastasis ,Pneumonectomy - Published
- 1974
14. [Bronchial adenomas and their significance]
- Author
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J, BALO, D, KASSAY, and A, BIKFALVI
- Subjects
Adenoma ,Lung Neoplasms ,Neoplasms ,Bronchial Neoplasms ,Bronchi - Published
- 1955
15. The results of the Monaldi process during the treatment of pulmonary suppurations
- Author
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A, BIKFALVI
- Subjects
Lung Abscess ,Lung ,Abscess - Published
- 1949
16. [Surgical indications of paratracheobronchial tuberculous adenopathies]
- Author
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A, Bikfalvi and W, Valentiner
- Subjects
Adult ,Male ,Rupture ,Pulmonary Atelectasis ,Suture Techniques ,Bronchial Diseases ,Bronchography ,Middle Aged ,Tuberculosis, Lymph Node ,Bronchiectasis ,Postoperative Complications ,Methods ,Humans ,Female ,Pneumonectomy ,Tuberculosis, Pulmonary - Published
- 1972
17. [Experimental studies of restoration of tracheo-bronchial tree continuity by means of grafts]
- Author
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A, Bikfalvi
- Subjects
Trachea ,Dogs ,Methods ,Animals ,Transplantation, Homologous ,Bronchi ,Bronchial Arteries ,Transplantation, Autologous - Published
- 1970
18. Nouveaux mécanismes du développement des tumeurs cérébrales
- Author
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GUYON, Joris, Laboratoire Angiogenèse et Micro-environnement des Cancers (LAMC), Université Sciences et Technologies - Bordeaux 1 (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bordeaux, Andreas Bikfalvi, STAR, ABES, Bikfalvi, Andreas, Javerzat, Sophie, Junier, Marie-Pierre, Chevet, Eric, and Carriere-Pazat, Audrey
- Subjects
Glioblastome ,Metabolism ,Lactate dehydrogenases ,Invasion ,Angiogenèse ,Lactate déshydrogénases ,Angiogenesis ,[SDV.BC]Life Sciences [q-bio]/Cellular Biology ,Spheroids ,Glioblastoma ,Spheroïdes ,[SDV.BC] Life Sciences [q-bio]/Cellular Biology ,Metabolisme - Abstract
Glioblastoma (GBM) is the most common and malignant primary brain tumor in adults. It can be recognized by its angiogenic and invasive growth, in addition to its altered metabolism.To study GBM, we developed three-dimensional models to better mimic its complex architecture of tumors. We have also refined in vitro methods, such as spheroid growth or invasion in collagen I matrix, to analyze certain characteristics of GBMs.Diffuse infiltration of GBMs complicates therapeutic management and is the cause of tumor recurrence. Invading cells into the healthy brain may form new tumor foci from the original tumor. A proteomic analysis of laser microdissection-captured human tumor pieces revealed potential actors of tumor invasion. PLP1 (proteolipid protein 1) and DNM1 (dynamin-1) was found enriched in the invasive part. In vitro inhibition of these protein lead to decrease GBM invasion and may represent potential therapeutic targets.By adapting their glycolytic or oxidative metabolism, GBM stem-like cells are able to resist chemo- and radiotherapy. Lactate is a central metabolite in brain physiology, involved in the astrocyte-neuron lactate shuttle, but also contributes to tumor development. We show herein that lactate fuels GBM anaplerosis by replenishing the TCA cycle in absence of glucose. Lactate dehydrogenases (LDH) catalyze the interconversion of pyruvate and lactate. Deletion of either LDHA or LDHB did not alter significantly GBM growth and invasion. However, ablation of both LDH isoforms led to a reduction of tumor growth, and, consequently, to an increase in mouse survival. Comparative transcriptomics and metabolomics revealed metabolic rewiring involving high oxidative phosphorylation (OxPhos) in the double LDHA/B KO group which sensitized tumors to cranial irradiation, massively improving mice survival. Survival was also increased when control mice were treated by an antiepileptic which targets LDH activity. Taken together, this highlights the complex metabolic network in which both LDH A and B are integrated and underscores that combined inhibition of LDHA and B is necessary to impact tumor development., Le glioblastome (GBM) est la tumeur cérébrale maligne la plus fréquente et la plus agressive chez l’adulte. Il est hautement prolifératif et invasif et se caractérise par une forte angiogenèse et la présence d’un métabolisme altéré.Afin de mieux comprendre son développement, nous avons créé des modèles cellulaires tridimensionnels permettant de se rapprocher au mieux de l’architecture complexe de la tumeur. Nous avons également affiné des méthodes in vitro, tels que des essais de croissance ou d’invasion en collagène de type I, pour analyser certaines caractéristiques des GBMs.L’infiltration diffus des GBMs complique la prise en charge thérapeutique et est à l’origine des récidives tumorales. Les cellules qui envahissent le parenchyme cérébral sain peuvent former de nouveaux foyers tumoraux à distance de la tumeur originelle. En utilisant une analyse de protéomique sur des échantillons de tumeurs humaines dans des cerveaux de souris récupérées par microdissection laser, nous avons identifié de potentiels acteurs de l’invasion tumorale. Les protéines PLP1 (proteolipid protein 1) et DNM1 (dynamin-1) ont été retrouvées enrichies dans la partie invasive. Leur inhibition in vitro a permis la réduction de la capacité invasive des GBMs et pourrait représenter de potentielles cibles thérapeutiques.En adaptant son métabolisme glycolytique et oxydatif, les cellules de GBM sont capables de résister à la chimio- et radiothérapie. Le lactate est un des métabolites centraux de la physiologie cérébrale, il est impliqué dans la navette astrocyte-neurone ainsi que dans le développement tumoral. En l’absence de glucose, le lactate alimente la production d’énergie des GBMs par le biais du cycle de Krebs. Les lactates déshydrogénases (LDHs) sont les enzymes qui catalysent l’interconversion du pyruvate et du lactate. La simple perte d’expression des isoformes LDHA ou LDHB ne perturbe pas significativement le développement des GBMs. Cependant, la double extinction de LDHA et LDHB (KO LDHA/B) induit une réduction de la croissance tumorale, de l’invasion et en conséquence, allonge la survie des souris. Les analyses comparatives des données de transcriptomique et de métabolomique révèlent que la lignée double KO LDHA/B augmente le métabolisme oxydatif sensibilisant la tumeur à l’irradiation et augmentant la survie des souris. L’utilisation d’un médicament antiépileptique inhibiteur de l’activité de LDHA et LDHB a permis d’augmenter la survie des souris en association avec le bevacizumab, un médicament anticancéreux ciblant l’angiogenèse. Cette étude met en évidence le réseau métabolique complexe dans lequel LDHA et LDHB sont intriqués. Elle souligne l’importance de la double inhibition de LDHA/LDHB pour impacter le développement tumoral.
- Published
- 2021
19. Nanoparticules polymères ciblant le récepteur CXCR3 : élaboration et évaluation sur modèles de tumeur
- Author
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Rodrigues, Laura, Laboratoire de Chimie des Polymères Organiques (LCPO), Centre National de la Recherche Scientifique (CNRS)-Institut Polytechnique de Bordeaux-Ecole Nationale Supérieure de Chimie, de Biologie et de Physique (ENSCBP)-Université de Bordeaux (UB)-Institut de Chimie du CNRS (INC), Université de Bordeaux, Sébastien Lecommandoux, and Andreas Bikfalvi
- Subjects
Self-Assembly ,Cxcr3 ,Copolymères à bloc ,[CHIM.POLY]Chemical Sciences/Polymers ,Active targeting ,Auto-Assemblage ,Nanoparticules ,Nanoparticles ,Block copolymers ,Ciblage actif - Abstract
This thesis deals with the elaboration of polymeric nanoparticles functionalized by the ligand SCH546738 to target the CXCR3 receptor overexpressed in human healthy or tumoral cells. Poly(trimethylene carbonate-b-Poly(ethylene glycol) (PTMC-b-PEG) blocks copolymers and PTMC-b-PEG-SCH546738 synthesis, then their self-assembly with different ratios in water, and finally biological activity in vitro of these different nanoparticles were studied. A serie of PTMC-b-PEG with different hydrophilic mass fractions f (between 34 and 6%) were obtained by ring opening polymerization (ROP) of trimethylene carbonate (TMC) initiated by a block PEG (MW: 2000 g/mol). Self-assembly studies showed that the hydrophilic mass fraction was related to the morphology of the nano objects (micelles and vesicles) and that size and morphology of nano objects can be changed by the self-assembly protocol. PTMC-b-PEG-SCH546738 were obtained by the convergent coupling between PEG-SCH546738 and PTMC block. The co self-assembly of functionalized and not functionalized copolymers was done by nanoprecipitation controlled by a microfluidic system that allows monodisperse polymersomes with controlled size to be produced. The molar percentage of SCH546738 at the surface of polymersomes was fixed at 5, 10 and 20 %, and with the control nanoparticle, these samples were tested in vitro on HEK 293 and U87 cells overexpressing the CXCR3-A. The influence of the ligand and its percentage on nanoparticles internalization and signaling pathways blocking on cells were analyzed.; La thèse présentée porte sur l’élaboration de nanoparticules polymères fonctionnalisées par le ligand SCH546738 afin de cibler le récepteur CXCR3 surexprimé sur les cellules cancéreuses. La synthèse des copolymères à blocs Poly(triméthylène carbonate)-b-Poly(éthylène glycol) (PTMCb- PEG) et PTMC-b-PEG-SCH546738, puis leurs auto-assemblages dans l’eau avec des pourcentages différents de l’un par rapport à l’autre et enfin l’activité biologique de ces nanoparticules in vitro ont été réalisés. Une série de PTMC-b-PEG de fraction hydrophile massique f différentes (entre 34 et 6%) ont été obtenus par polymérisation par ouverture de cycle (ROP) du monomère triméthylène carbonate (TMC) amorcée par un PEG (MW= 2000 g/mol). Les études d’auto-assemblage ont montré que la fraction hydrophile était liée à la morphologie des objets obtenus (micelles et vésicules) et que la taille et la morphologie pouvaient être modulées en fonction du protocole utilisé. Des PTMC-b-PEG-SCH546738 ont été obtenus par couplage convergent entre le PEG-SCH546738 et le bloc PTMC. Le co auto-assemblage entre les copolymères fonctionnalisés et non fonctionnalisés a été réalisé par nanoprécipitation contrôlée par un système de microfluidique qui permet d’obtenir des polymersomes monodisperses de tailles contrôlées. Le pourcentage molaire de SCH546738 en surface des polymersomes a été fixé à 5, 10 et 20 % et à l’aide d’une nanoparticule contrôle ces échantillons ont pu être testés in vitro sur cellules HEK 293 et U87 surexprimant le CXCR3-A. L’influence du ligand et son pourcentage sur l’internalisation des nanoparticules à différents temps et sur le blocage des voies de signalisation des cellules cancéreuses ont été observés.
- Published
- 2018
20. CXCR3-targeting polymer nanoparticles : synthesis and evaluation on tumor models
- Author
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RODRIGUES, Laura, Laboratoire de Chimie des Polymères Organiques (LCPO), Centre National de la Recherche Scientifique (CNRS)-Institut Polytechnique de Bordeaux-Ecole Nationale Supérieure de Chimie, de Biologie et de Physique (ENSCBP)-Université de Bordeaux (UB)-Institut de Chimie du CNRS (INC), Université de Bordeaux, Sébastien Lecommandoux, Andreas Bikfalvi, STAR, ABES, Philippe Barthélémy [Président], Amandine Hurbin [Rapporteur], Jean Coudane [Rapporteur], Nancy Lauth de Viguerie, Elisabeth Garanger, and Clotilde Billottet
- Subjects
Self-Assembly ,Cxcr3 ,Copolymères à bloc ,[CHIM.POLY] Chemical Sciences/Polymers ,[CHIM.POLY]Chemical Sciences/Polymers ,Active targeting ,Auto-Assemblage ,Nanoparticules ,Nanoparticles ,Block copolymers ,Ciblage actif - Abstract
This thesis deals with the elaboration of polymeric nanoparticles functionalized by the ligand SCH546738 to target the CXCR3 receptor overexpressed in human healthy or tumoral cells. Poly(trimethylene carbonate-b-Poly(ethylene glycol) (PTMC-b-PEG) blocks copolymers and PTMC-b-PEG-SCH546738 synthesis, then their self-assembly with different ratios in water, and finally biological activity in vitro of these different nanoparticles were studied. A serie of PTMC-b-PEG with different hydrophilic mass fractions f (between 34 and 6%) were obtained by ring opening polymerization (ROP) of trimethylene carbonate (TMC) initiated by a block PEG (MW: 2000 g/mol). Self-assembly studies showed that the hydrophilic mass fraction was related to the morphology of the nano objects (micelles and vesicles) and that size and morphology of nano objects can be changed by the self-assembly protocol. PTMC-b-PEG-SCH546738 were obtained by the convergent coupling between PEG-SCH546738 and PTMC block. The co self-assembly of functionalized and not functionalized copolymers was done by nanoprecipitation controlled by a microfluidic system that allows monodisperse polymersomes with controlled size to be produced. The molar percentage of SCH546738 at the surface of polymersomes was fixed at 5, 10 and 20 %, and with the control nanoparticle, these samples were tested in vitro on HEK 293 and U87 cells overexpressing the CXCR3-A. The influence of the ligand and its percentage on nanoparticles internalization and signaling pathways blocking on cells were analyzed., La thèse présentée porte sur l’élaboration de nanoparticules polymères fonctionnalisées par le ligand SCH546738 afin de cibler le récepteur CXCR3 surexprimé sur les cellules cancéreuses. La synthèse des copolymères à blocs Poly(triméthylène carbonate)-b-Poly(éthylène glycol) (PTMCb- PEG) et PTMC-b-PEG-SCH546738, puis leurs auto-assemblages dans l’eau avec des pourcentages différents de l’un par rapport à l’autre et enfin l’activité biologique de ces nanoparticules in vitro ont été réalisés. Une série de PTMC-b-PEG de fraction hydrophile massique f différentes (entre 34 et 6%) ont été obtenus par polymérisation par ouverture de cycle (ROP) du monomère triméthylène carbonate (TMC) amorcée par un PEG (MW= 2000 g/mol). Les études d’auto-assemblage ont montré que la fraction hydrophile était liée à la morphologie des objets obtenus (micelles et vésicules) et que la taille et la morphologie pouvaient être modulées en fonction du protocole utilisé. Des PTMC-b-PEG-SCH546738 ont été obtenus par couplage convergent entre le PEG-SCH546738 et le bloc PTMC. Le co auto-assemblage entre les copolymères fonctionnalisés et non fonctionnalisés a été réalisé par nanoprécipitation contrôlée par un système de microfluidique qui permet d’obtenir des polymersomes monodisperses de tailles contrôlées. Le pourcentage molaire de SCH546738 en surface des polymersomes a été fixé à 5, 10 et 20 % et à l’aide d’une nanoparticule contrôle ces échantillons ont pu être testés in vitro sur cellules HEK 293 et U87 surexprimant le CXCR3-A. L’influence du ligand et son pourcentage sur l’internalisation des nanoparticules à différents temps et sur le blocage des voies de signalisation des cellules cancéreuses ont été observés.
- Published
- 2018
21. Implication de la Protéine Tyrosine Phosphatase PRL-2 dans le développement vasculaire
- Author
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POULET, Mathilde, STAR, ABES, Bikfalvi, Andreas, Tremblay, Michel, Couffinhal, Thierry, Garmy-Susini, Barbara, and Pagès, Gilles
- Subjects
[SDV.SA] Life Sciences [q-bio]/Agricultural sciences ,Invasion ,Angiogenèse ,Angiogenesis ,PRL-2 ,VEGF-A ,Migration - Abstract
The three Phosphatase of Regenerative Liver (PRL-1, -2, -3) represent an intriguing group of protein tyrosine phosphatases that has been implicated in a number of diseases. They have gained much attention in the context of cancer. Indeed, they have been constantly associated with metastasis, cell proliferation, cell invasion and migration. To date, however, little is known about their physiological function and no biological substrates have been clearly identified. All three PRLs are highly conserved among mammals, underscoring the idea that they might have important roles in cellular functions. Characterization of the PRL-2 knockout mouse indicates that this phosphatase is likely involved throughout development. Protein phosphorylation is implicated in angiogenesis by playing critical and reversible functions in cell signaling pathways. This prompted us, in the frame of this thesis, to investigate the role of PRL-2 in vascular morphogenesis using both in vitro models and genetic loss-of-function mouse models. In the retinal angiogenesis mouse model, we found that PRL-2 deletion leads to delay in the formation of the retinal vascular plexus with a reduction of the advancing vasculature across the vitreal surface. Furthermore, excessive angiogenesis and branching at the leading edge in 6 day old pups is observed. Indeed, the growing front of PRL-2 KO mouse retinas showed a higher vascular density due to active, multidirectional hypersprouting of the vasculature. This data introduces PRL-2 as a potential component of the complex signaling network that orchestrates neo-angiogenesis. Based on these findings, we have examined whether the absence of PRL-2 can modify the behavior of endothelial cells in vitro. We showed an altered migration in various assays. In particular, sprouting in in vitro angiogenesis assays is altered, which is in agreement with the in vivo data. By using several siRNA, we showed that the signaling pathway of PRL-2 is dependent to VEGF/VEGFR signaling. Indeed, the stimulation of endothelial cells by VEGF is dependant of the presence or absence of PRL-2. Furthermore, other targets altered by PRL-2 downregulation, are Notch and the Hey2 transcription factor, which is consistent with in vivo data as we showed a strikingly effect on arteriovenous differentiation. Taken together, these data introduce PRL-2 as a novel component of the complex signaling network that orchestrates developmental and, possibly, pathological angiogenesis., Les trois enzymes de la famille PRL (PRL-1,2,3), représentent un groupe de protéines tyrosine phosphatases intrigantes, impliquées dans un très grand nombre de maladies. Elles ont gagné beaucoup d'attention ces dernières années dans le contexte tumoral puisqu’elles sont très fréquemment associées à la formation de métastases, la prolifération cellulaire, l'invasion et la migration cellulaire. Bien que les propriétés oncogéniques des PRLs ne fassent plus de doute, ces phosphatases sont très peu caractérisées dans un contexte physiologique. Ainsi, aucun substrat biologique n’a été clairement identifié à ce jour et très peu de fonctions biologiques leurs sont associées, malgré un très haut degré de conservation inter-espèce suggérant un rôle critique de ces protéines dans les fonctions cellulaires. La caractérisation de la souris déficiente pour PRL-2 indique que cette phosphatase est probablement impliquée tout au long du développement. La phosphorylation des protéines est un phénomène important pour la régulation de l'angiogenèse en jouant des fonctions critiques et réversibles sur les voies de signalisation cellulaire. Cela nous a incités, dans le cadre de cette thèse, à étudier le rôle de PRL-2 dans la morphogenèse vasculaire en utilisant à la fois des modèles in vitro et un modèle de souris déficientes pour PRL-2. Dans le modèle murin de l'angiogenèse rétinienne, nous avons trouvé que la délétion de PRL-2 entraîne un retard dans la formation du plexus vasculaire avec une réduction de la vascularisation. De plus, on observe une angiogenèse et une ramification excessive au niveau du front vasculaire chez les souriceaux. En effet, le front de croissance des rétines de souris PRL-2 KO présente une densité vasculaire plus élevée associée à un bourgeonnement endothélial actif et multidirectionnel. Ces données présentent PRL-2 comme un composant potentiel du réseau de signalisation complexe qui orchestre la néo-angiogenèse. Nous avons ensuite examiné les conséquences de la perte de PRL-2 sur le comportement des cellules endothéliales in vitro. Nous avons observé des modifications de migration et d’invasion dans différents modèles. En particulier, l’absence de PRL-2 accroît le bourgeonnement de capillaires dans des tests d'angiogenèse in vitro, ce qui est en accord avec les données in vivo. En utilisant plusieurs siRNA, nous avons montré que la voie de signalisation de PRL-2 est liée à la signalisation VEGF/VEGFR. En effet, la stimulation des cellules endothéliales par le VEGF dépend de la présence ou de l'absence de PRL-2. En outre, une autre voie altérée par la régulation négative de PRL-2, est celle de Notch ainsi que celle du facteur de transcription Hey2. Ceci est cohérent avec les données in vivo où nous avons démontré un effet important sur la différenciation artérioveineuse. Ces données introduisent PRL-2 en tant que composant novateur du réseau de signalisation complexe qui orchestre l'angiogenèse développementale et, éventuellement, pathologique.
- Published
- 2017
22. Implication of CXCR3 in tumor progression : a new therapeutical target
- Author
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Boyé, Kevin, STAR, ABES, Laboratoire Angiogenèse et Micro-environnement des Cancers (LAMC), Université Sciences et Technologies - Bordeaux 1-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bordeaux, Clotilde Billottet, Billottet, Clotilde, Eichmann, Anne, Badaut, Jerôme, Bikfalvi, Andreas, Dedieu, Stéphane, and Ruegg, Curzio
- Subjects
Glioblastome ,CXCR3 ,CXCL4L1 ,LRP1 ,PDAC ,hemic and immune systems ,[SDV.BC]Life Sciences [q-bio]/Cellular Biology ,Nanoparticule ,stomatognathic diseases ,Chimiokine ,stomatognathic system ,immune system diseases ,Chemokine ,Nanobodies ,skin and connective tissue diseases ,Glioblastoma ,[SDV.BC] Life Sciences [q-bio]/Cellular Biology - Abstract
CXCR3 belongs to the G-protein-coupled receptors family. With its ligands, the CXC chemokines, CXCR3 regulates several biological functions and plays important roles in angiogenesis, inflammation and cancer. The interaction with CXCR3 is rather complex due to the presence of distinct spliced isoforms. CXCR3-A is known to promote cell proliferation, survival, and migration while CXCR3-B leads to cell growth inhibition.The human glioblastoma cell model, U87, was used to study the molecular mechanisms regulating the activity and trafficking of CXCR3 isoforms in tumor cells. CXCR3 has been reported as the functional receptor for the angiostatic activity of CXCL4 and its variant CXCL4L1. Depending on their oligomerization status, these two chemokines present preferential interaction with CXCR3 isoforms. Activation of CXCR3-A leads to an important conformational change and induces pro-migratory signaling pathways. Studies on the vesicular trafficking highlight the importance of the clathrin and the Trans-Golgi network for both internalization and recycling of CXCR3-A. For the first time, LRP-1 is identified as a new partner of CXCR3-A. LRP1 is not only recognized as an endocytic receptor but also as a signaling protein. LRP1 interacts with CXCR3-A via its extracellular α subunit and regulates CXCR3-A conformation, trafficking and pro-tumoral activity.Pancreatic ductal adenocarcinoma cell models were used to characterize CXCL4L1 as a pro-tumoral factor that activates CXCR3-A in tumor cells. For the first time, CXCL4L1 appears as an important biomarker for pancreatic cancer progression.In the different cell models, signaling pathways of CXC chemokine/CXCR3-A lead to an increase in tumor invasive properties. At the molecular level, the association of CXCR3 with various proteins (ligands and partners) is essential to regulate tumor cell biological functions.The nanoparticles are now known as a new generation of therapeutic antibodies with many advantages over conventional antibodies. Thus, the development of nanoparticles associated to CXCR3 inhibitors appears as a new promising pharmacological targeted strategy to treat cancer., CXCR3 appartient à la famille des récepteurs couplés aux protéines G. Avec ses ligands, les chimiokines CXC, CXCR3 régule diverses fonctions biologiques et participe à de nombreux processus comme l’angiogenèse, l’inflammation et le cancer. La complexité de CXCR3 provient de son épissage alternatif qui conduit à des isoformes distinctes. CXCR3-A est reconnu pour promouvoir la prolifération, la survie et la migration cellulaire tandis que CXCR3-B induit des signaux inhibiteurs de la croissance cellulaire.Le modèle cellulaire U87, dérivé d’un glioblastome humain, a été utilisé afin d’étudier les mécanismes moléculaires régulant l'activité et le trafic des isoformes de CXCR3 dans les cellules tumorales. CXCR3 est le récepteur fonctionnel de l’activité angiostatique de CXCL4 et son variant CXCL4L1. En fonction de leur état d'oligomérisation, ces deux chimiokines ont des interactions préférentielles avec les isoformes de CXCR3. L’activation de CXCR3-A conduit à un important changement conformationnel et induit des voies de signalisation pro-migratoires. L’étude du trafic souligne l’importance de la clathrine et du réseau Trans-Golgi dans l’internalisation et le recyclage de CXCR3-A. Pour la première fois, LRP-1 a été identifié comme nouveau partenaire de CXCR3-A. LRP1 n’est pas seulement reconnu comme un récepteur de l’endocytose mais également comme une protéine de la signalisation. LRP1 interagit avec CXCR3-A au niveau extracellulaire et régule sa conformation, son trafic et son activité pro-tumorale.L'utilisation de modèles cellulaires d'adénocarcinome pancréatique a permis de caractériser CXCL4L1 comme facteur pro-tumoral, via l’activation de CXCR3-A dans les cellules tumorales. CXCL4L1 apparait pour la première fois comme un biomarqueur important dans la progression du cancer pancréatique.Dans les différents modèles, les signalisations chimiokines CXC/CXCR3-A induisent une augmentation des propriétés invasives tumorales. Au niveau moléculaire, l’association de CXCR3 à diverses protéines (ligands et partenaires) est essentielle pour réguler les fonctions biologiques de la cellule tumorale.Les nanoparticules sont désormais connues comme une nouvelle génération d'anticorps thérapeutiques présentant de nombreux avantages par rapport aux anticorps conventionnels. Ainsi, le développement de nanoparticules associées à des inhibiteurs de CXCR3 apparaît comme une nouvelle stratégie thérapeutique anti-tumorale prometteuse.
- Published
- 2016
23. Rôles des facteurs angiogéniques dans le système nerveux central
- Author
-
GUÉRIT, Sylvaine, Bikfalvi, Andreas, Feige, Jean-Jacques, Branchereau, Pascal, Fortin, Gilles, and Pagès, Gilles
- Subjects
Glioblastome ,TGFbeta ,Matrice extracellulaire ,Moelle épinière ,Ire1 ,Vegf ,Activité synaptique ,Réaction astrocytaire ,Développement embryonnaire
24. Synthèse de molécules fluorées pour le développement d'un nouvel outil de nano-imagerie : application à l'imagerie de l'angiogénèse pathologique
- Author
-
LAVIELLE, Sébastien, Déléris, Gérard, Gionnet, Karine, Bikfalvi, Andreas, Dollé, Frédéric, Lavielle, Bernard, Lasne, Marie-Claire, and Vidal, Michel
- Subjects
Mots cles français
25. Implication fonctionnelle des vaisseaux sanguins cérébraux dans le processus de consolidation mnésique
- Author
-
GIACINTI, Anaïs, Macrez, Nathalie, Bontempi, Bruno, Roullet, Pascal, Bikfalvi, Andreas, Brunet, Isabelle, and Poucet, Bruno
- Subjects
Signalisation calcique ,Angiogenèse ,Réseau vasculaire cérébral ,Consolidation mnésique
26. Identification of new potential prognosis factor and therapeutically targets in kidney cancer
- Author
-
Souleyreau, Wilfried, Auguste, Patrick, Bernardi, Henri, Rezvani, Hamid Reza, Bikfalvi, Andreas, Pyronnet, Stéphane, Pagès, Gilles, and STAR, ABES
- Subjects
Cancer du rein ,Renal Carcinoma ,Kidney Cancer ,Interleukin-34 ,[SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology ,Metastasis ,Collagène ,Renca ,Matrigel ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,Interleukine-34 ,Carcinome Rénal ,Fibronectine ,Collagen ,Fibronectin ,Métastase - Abstract
Kidney cancer is one of the 10 commonest human cancers. To date, no biomolecular markers are available in this type of cancer, and in the case of metastatic cancer, the therapeutic arsenal is still inefficient. The different processes involved in cancer progression are still poorly understood. Understanding those processes could highlight new therapeutic targets, and new prognostic or diagnostic biomolecular markers of this disease. For a first project, a new innovative model has been generated from a murine RCC cell line as a tool to understand cancer progression mechanisms and to identify new therapeutic target and new biomolecular markers in kidney cancer. This model of sequential reimplantation of cancer cells isolated from primary tumours or metastases allowed us to generate different cell lines showing increased aggressiveness after passages. Using a systems biology strategy, this model will allow us to identify new potential therapeutic targets and new biomolecular markers in RCC. Interleukin-34 is an example of an already selected target, showing the power of the model generated. For a second project, the role of some members of extracellular matrix (collagen type I, fibronectin, matrigel).was studied using this same murine RCC cell line. This study demonstrated the potential pro-invasive and pro-metastatic roles of collagen type I deposition in tumors. Collagen-activated receptors are proposed as mediators of the effect induced by collagen type I in this model. Those two projects have and will continue to contribute to a better understanding of cancer progression mechanisms, and will bring out new biomolecular markers and new therapeutic targets., Le cancer du rein compte parmi les 10 types de cancers les plus fréquents chez l’Homme. Il n’existe aujourd’hui aucun marqueur biomoléculaire dans ce type de cancer, et dans le cas d’un cancer métastatique, l’arsenal thérapeutique aujourd’hui disponible manque d’efficacité. Les différents processus mis en jeu lors de la progression tumorale sont encore mal connus. La connaissance de ces processus pourrait permettre de mettre en évidence de nouvelles cibles thérapeutiques, ainsi que des marqueurs biomoléculaires pronostiques ou diagnostiques de la maladie. Dans un premier projet, et afin de mieux comprendre les mécanismes de la progression tumorale et d’identifier de nouvelles cibles thérapeutiques potentielles et de nouveaux marqueurs biomoléculaires dans le cancer du rein, un nouveau modèle innovant a été généré à partir d’une lignée tumorale de RCC murine. Ce modèle de réimplantations successives de cellules tumorales issues de tumeur primaire ou de métastases a permis de générer différentes lignées cellulaires montrant une agressivité accrue au cours des passages. En utilisant une stratégie de biologie des systèmes, ce modèle pourra permettre de mettre en évidence des cibles d’études prometteuses qui pourraient être de nouvelles cibles thérapeutiques ou de nouveaux marqueurs biomoléculaires dans le RCC. L’interleukine-34 est l’exemple d’une cible d’étude d’ores et déjà été sélectionnée, mettant en évidence la puissance du modèle généré. Dans un second projet, les rôles de certains membres de la matrice extracellulaire tumorale ont été évalués en utilisant cette même lignée de RCC murine (collagène de type I, fibronectine, matrigel). Cette étude a permis de mettre en évidence le potentiel pro-invasif et pro-métastatique du dépôt de collagène de type I dans les tumeurs. Des récepteurs activés par le collagène sont proposés comme potentiellement impliqués dans les effets induits par le collagène de type I dans le modèle. Ces deux projets permettent et permettront de mieux comprendre certains mécanismes de la progression tumorale, ainsi que de mettre en évidence des marqueurs biomoléculaires et de nouvelles cibles thérapeutiques.
27. [Science, truth and beliefs].
- Author
-
Bikfalvi A
- Subjects
- Dissent and Disputes, Ethical Relativism, Evidence-Based Medicine education, Human Characteristics, Humans, Mythology, Social Environment, Culture, Knowledge, Science
- Abstract
This article aims at discussing some aspects of the relationship between science, truth and belief. I will primarily focus on the scientific activity in the biological and medical sciences and how it relates to the notion of truth and belief and not discuss the relationship with specific religions. Science has specific methodologies to obtain knowledge. Philosophers have analyzed how scientific knowledge is acquired and have tried to identify its characteristics and to establish some general rules of how knowledge through science is gained. Radical theorists have disputed the value of the scientific method despite science's indisputable successes. If science is a rational activity, it is not free from belief. Belief can have a positive and negative impact on the acquisition of scientific knowledge and the idea of human nature. These different issues will be discussed in depth in this article., (© 2018 médecine/sciences – Inserm.)
- Published
- 2018
- Full Text
- View/download PDF
28. [Tumoral angiogenesis: models, targets and inhibition].
- Author
-
Bikfalvi A
- Subjects
- Angiogenesis Inhibitors pharmacology, Angiogenesis Inhibitors therapeutic use, Animals, Cell Hypoxia genetics, Chick Embryo, Gene Expression Regulation, Developmental, Humans, Hypoxia-Inducible Factor 1, alpha Subunit physiology, Unfolded Protein Response drug effects, Unfolded Protein Response physiology, Chorioallantoic Membrane blood supply, Endoplasmic Reticulum physiology, Neoplasms blood supply, Neovascularization, Pathologic drug therapy, Neovascularization, Pathologic genetics, Neovascularization, Pathologic physiopathology, Neovascularization, Physiologic genetics
- Abstract
Angiogenesis is a basic process during development and in pathology as well. The molecular networks involved in angiogenesis are not totally understood. We have recently developed a new model for tumoral angiogenesis in the chicken embryo, which allows large scale studies. On the other hand we have uncovered a new induction pathway, which involves stress of the endoplasmic reticulum. These investigations open up novel prospects for the future.
- Published
- 2009
- Full Text
- View/download PDF
29. [Experimental approaches to study in vivo angiogenesis].
- Author
-
Kilarski W and Bikfalvi A
- Subjects
- Animals, Blood Vessels embryology, Chick Embryo, Chorioallantoic Membrane blood supply, Collagen, Corneal Neovascularization etiology, Drug Combinations, Ear, External blood supply, Laminin, Models, Animal, Neoplasms blood supply, Neovascularization, Pathologic diagnosis, Proteoglycans, Rabbits, Neovascularization, Pathologic embryology, Neovascularization, Physiologic physiology
- Abstract
Angiogenesis has become a major issue in oncology. Different in vivo angiogenesis assays have been developed in order to better understand fundamental aspects of vascular development or to investigate the effect of therapeutic molecules on blood vessel growth. In this article, we will briefly review the main in vivo angiogenesis assays relevant to oncology and discuss their advantages and disadvantages.
- Published
- 2007
30. [Tumor angiogenesis].
- Author
-
Bikfalvi A
- Subjects
- Angiopoietins physiology, Humans, Vascular Endothelial Growth Factor A physiology, Fibroblast Growth Factors physiology, Lymphangiogenesis physiology, Neoplasms blood supply, Neovascularization, Pathologic etiology, Vascular Endothelial Growth Factors physiology
- Abstract
Following the work of Folkman, it appears that angiogenesis, which consists in the formation of new blood vessels able to deliver oxygen and nutriments to tumor cells, is a major step in the evolution of tumors, which can only grow after the onset of the angiogenic switch. Numerous factors play a role in angiogenesis stimulation or inhibition : the vascular endothelial growth factor and fibroblastic growth factors as well as angiopoietin are proangiogenic, whereas angiostatin and platelet factor 4 are anti-angiogenic. The discovery of these molecules and of the molecular mechanisms of their activity allowed the identification of new therapeutic targets, which appear relevant for the treatment of cancer.
- Published
- 2007
31. [Understanding in treating gliomas: an adequate experimental model for each question].
- Author
-
Javerzat S, Bikfalvi A, and Hagedorn M
- Subjects
- Animals, Chick Embryo, Humans, Mice, Microarray Analysis methods, Neoplasm Transplantation methods, Rats, Brain Neoplasms genetics, Brain Neoplasms pathology, Chorioallantoic Membrane, Disease Models, Animal, Glioma genetics, Glioma pathology
- Abstract
Malignant glioma are especially difficult to model in vivo. Here we review the most recent strategies for designing relevant models of glioma. These should greatly contribute to identification of new tumor regulating molecules and facilitate testing of inhibitors to be used in therapeutical trials as well as the drug resistance that they might confer.
- Published
- 2005
32. [Tumor angiogenesis].
- Author
-
Bikfalvi A
- Subjects
- Growth Substances pharmacology, Humans, Neoplasms drug therapy, Neoplasms physiopathology, Signal Transduction, Angiogenesis Inhibitors pharmacology, Neoplasms blood supply, Neovascularization, Pathologic physiopathology
- Abstract
Recent advances in the understanding of the molecular control of angiogenesis have shown that this process is essential for tumor development and spread. The identification of a great many of ligands, receptors or intracellular signalling molecules have allowed to unravel some of the regulatory loops involved. Especially noteworthy is the fact that developmental regulators seem now to play a role in tumor angiogenesis. Furthermore, these studies have allowed to identify novel therapeutic targets and to develop novel molecules and strategies for cancer therapy. This indicates that tumor angiogenesis is at present a major focus of cancer research., (Copyright John Libbey Eurotext 2003.)
- Published
- 2003
33. [Role of fibroblast growth factor-2 in tumor angiogenesis].
- Author
-
Bikfalvi A
- Subjects
- Animals, Humans, Fibroblast Growth Factor 2 physiology, Neovascularization, Pathologic
- Abstract
Angiogenesis reflects a balance between stimulating and inhibitory factors, among which fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor (VEGF) play a central role. FGF-2 stimulates endothelial cell growth and migration and enhances angiogenesis, both in vitro and in vivo. FGF-2 binds to a specific receptor (FGF R1) at the surface of endothelial cells. In addition to its extracellular effects, FGF-2 exerts intracellular effects that seem to be independent from tyrosine kinase-type receptors. FGF-2 is produced by several tumor types, including brain tumors, skin tumors, and fibrosarcomas. FGF-2 may play a pivotal role in angiogenesis in these tumors.
- Published
- 1999
34. [Angiogenesis and neoangiogenesis].
- Author
-
Savona C, Javerzat S, Perollet C, and Bikfalvi A
- Subjects
- Angiogenesis Inducing Agents metabolism, Humans, Neovascularization, Pathologic enzymology, Urokinase-Type Plasminogen Activator metabolism, Endothelium, Vascular physiopathology, Neovascularization, Pathologic physiopathology, Neovascularization, Physiologic drug effects
- Abstract
Angiogenesis, the development of new capillary networks from the normal vasculature, is a fundamental process during embryogenesis. In adulthood, angiogenesis contributes to corpus luteum formation, placental implantation and wound healing and is also required in some pathological conditions such as several intraocular syndromes, growth of solid tumors, and metastasis. Many factors are involved in the regulation of neovascularisation among which FGF-2 (fibroblast growth factor-2) and VEGF (vascular endothelial growth factor) are considered as key inducers. Their biological activity is highly controlled by extracellular matrix components and angiostatic factors. Better understanding of the molecular mechanisms regulating angiogenesis should contribute to the development of new molecules to be used for the treatment of neovascularisation-linked diseases.
- Published
- 1997
35. [Angiogenesis and cancer].
- Author
-
Bikfalvi A, Javerzat S, Perollet C, and Savona C
- Subjects
- Humans, Neoplasm Invasiveness pathology, Neoplasm Metastasis pathology, Neoplasms blood supply, Growth Substances genetics, Growth Substances metabolism, Neoplasms pathology, Neovascularization, Pathologic
- Abstract
Tumor invasion and dissemination is tightly controlled by angiogenesis. In recent years, a number of angiogenic factors and inhibitors have been identified. However, the molecular mechanisms leading to this phenomenon are still incompletely understood. In this review, we focus on recent developments in the angiogenesis field. We will summarize our present knowledge about the molecular mechanisms involved in angiogenesis and about the factors that control this phenomenon. We will then shortly discuss the pharmacological modulation and the therapeutic and clinical implications for cancer biology.
- Published
- 1997
36. [Remarks on surgery of bronchial cancer].
- Author
-
Bikfalvi A
- Subjects
- Bronchial Neoplasms diagnosis, Bronchial Neoplasms diagnostic imaging, Humans, Mediastinoscopy, Neoplasm Metastasis diagnosis, Neoplasm Metastasis surgery, Pneumonectomy, Radiography, Bronchial Neoplasms surgery
- Published
- 1974
37. The results of the Monaldi process during the treatment of pulmonary suppurations.
- Author
-
BIKFALVI A
- Subjects
- Abscess, Lung, Lung Abscess
- Published
- 1949
38. [Bronchial adenomas and their significance].
- Author
-
BALO J, KASSAY D, and BIKFALVI A
- Subjects
- Adenoma, Bronchi, Bronchial Neoplasms, Lung Neoplasms, Neoplasms
- Published
- 1955
39. [Experimental studies of restoration of tracheo-bronchial tree continuity by means of grafts].
- Author
-
Bikfalvi A
- Subjects
- Animals, Bronchi blood supply, Bronchial Arteries anatomy & histology, Dogs, Methods, Trachea blood supply, Trachea pathology, Trachea surgery, Transplantation, Autologous, Transplantation, Homologous, Bronchi transplantation, Trachea transplantation
- Published
- 1970
40. [Surgical indications of paratracheobronchial tuberculous adenopathies].
- Author
-
Bikfalvi A and Valentiner W
- Subjects
- Adult, Bronchial Diseases etiology, Bronchiectasis etiology, Bronchiectasis surgery, Bronchography, Female, Humans, Male, Methods, Middle Aged, Pneumonectomy, Postoperative Complications, Pulmonary Atelectasis etiology, Rupture, Suture Techniques, Tuberculosis, Lymph Node complications, Bronchial Diseases surgery, Tuberculosis, Lymph Node surgery, Tuberculosis, Pulmonary complications
- Published
- 1972
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